1. family and parenting
2. children

Medicinski arhiv
č a s o p i s l jekara/liječnika bih
• Godina 2009 • volumen 63 • broj 3 •
Medical Archives
journal of physicians of BiH
• Year 2009 • Volume 63 • No 3 •
Časopis je indeksiran u bazama medline (www.pubmed.gov), ebsco (www.ebscohost.com)
Nepoznati autor: Zimski pejsaž.
i index copernicus (www.indexcopernicus.com)
ISSN 0350-199 X
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Medical Archives Journal of BiH Physicians
CONTENTS
original papers
124Contact Network and Satisfaction with Contacts in Children Whose Parents
Have Post Traumatic Stress Disorder
Zihnet Selimbasic, Osman Sinanovic, Esmina Avdibegovic, Nemina Kravic
128Etiološke karakteristike akutnih infekcija mokraćnog sistema stečenih u
zajednici kod odraslih hospitaliziranih bolesnika
EDITORIAL BOARD
Editor-In-Chief
Izet Masic
Secretary
Alma Zejnilovic
Technical editor
Mirza Hamzic
Lectors: Lejla Masic,
Dubravko Vanicek
MEMBERS OF THE
BOARD
Sebija Izetbegovic (Sarajevo, BiH),
Izet Hozo (Split, Croatia), Zlatko
Hrgovic (Franfurt, Germany), Zdenka
Krivokuca (Banja Luka,BiH), Dragica
Milinkic (Sydney, Australia),
Sahib Muminagic (Zenica, BiH),
Ljerka Ostojic (Mostar, BiH), Haris
Pandza (Sarajevo,BiH), Enra SuljicMehmedika (Sarajevo,BiH), Selim
Toromanovic (Bihac,BiH), Narcisa
Vavra-Hadziahmetovic (Sarajevo,BiH),
Muharem Zildzic (Tuzla,BiH), Adnan
Zubovic (Oxford, UK)
ADDRESS OF THE BOARD
Sarajevo, Cekalusa 90,
Tel: +387 33 444 714,
e-mail: avicena@lol.ba
www.avicenapublisher.org
PUBLISHED BY
Avicena d.o.o., Sarajevo,
Zaima Sarca 43
Bank account:
UNION banka Sarajevo, br.:
1020500000020077
SWIFT Code UBKSBA22,
Deutsche Bank AG, Franfurt am
Main (DEUTDEFF), Account No.
9365073 10 (EUR). IBAN BA 39
1020500000020077.
Medical Archive journal is published
five to six times per year (Feb, Apr,
Jun, Oct, Dec). Subscription for
individuals is 50 euros, for institutions
100 euros, and includes VAT and
postal services.
Journal is indexed in MEDLINE, EBSCO
and INDEX COPERNICUS - ICV for
2008 is 5,22
Etiological Factors of Community Acquired Urinary Tract Infections in Hospitalized Patients
Dilista Piljić, Sead Ahmetagić, Dragan Piljić, Muharem Zildžić, Humera Porobić
133Mikroalbuminurija i ultrazvučne karakteristike bubrega u djece i adolescenata
sa Dijabetes melitusom tip 1
Microalbuminuria and Ultrasound Characteristics of Kidneys in Children and Adolescents with Diabetes
Mellitus Type 1
Evlijana Hasanović, Denijal Tulumović, Goran Imamović, Senaid Trnačević
137Colposcopic Changes Based on Number of Sexual Partners, Births, and
Contraceptives Use
Myrvete Paçarada, Shefqet Lulaj, Gyltene Kongjeli, Niltene Kongjeli, Hana Qavdarbasha, Bujar Obërtinca
141Diagnostic Value of CEA in Pleural Fluid for Differential Diagnosis of Benign
and Malign Pleural Effusion
Tatjana Radjenovic-Petkovic, Tatjana Pejcic, Desa Nastasijević-Borovac, Milan Rancic, Danijela Radojkovic, Milan Radojkovic,
Ivanka Djordjevic
143Effects of Extracorporeal Shockwave Lithotripsy on Renal Vasculature and
Renal Resistive Index (RI)
Mustafa Hiros, Mirsad Selimovic, Hajrudin Spahovic, Sabina Sadovic
146Aerozagađenje i trend hospitalizacije djece zbog bronhoopstrukcije na
području Tuzlanskog kantona
Air Pollution and Hospital Admission Trends of Children with Bronchial Obstruction in Tuzla Canton
Devleta Hadžić, Nada Mladina, Farid Ljuca, Mustafa Bazardžanović
152Uticaj statina na postoperativni tretman pacijenata operiranih radi ugradnje
aortokoronarnih premoštenja
Effects of Statins on Postoperative Treatment of Patients After Aortocoronary Bypass Grafting
Mehmed Kulić, Mirza Dilić, Vjekoslav Gerc, Bećir Heljić
157Effectiveness of Diabetes Flow Sheet in Controlling Blood Pressure: Should
Family Medicine Teams in Zenica Use Recommended Guidelines?
Larisa Gavran, Olivera Batic-Mujanovic, Selmira Brkic, Sabina Nuhbegovic
160Collective Immunity of the Population from Endemic Zones of Hemorrhagic
Fever with Renal Syndrome in Kosovo
Sefedin Muçaj, Serbeze Kabashi, Salih Ahmeti, Isuf Dedushaj, Naser Ramadani, Tatjana Avsic-Zupanc
professional papers
163Liječenje Hallux valgusa osteotomijom prve kosti metatarzusa po Krameru
The Kramer Osteotomy in the Treatment of Hallux Valgus
Sahib Muminagić, Sanja Drljević, Amela Granić, Tarik Kapidžić, Mehmed Kovačević, Faruk Hodžić
reviews
166Perkutane koronarne intervencije bez „on-site“ kardiohirurške potpore
Percutaneous Coronary Interventions Without On-Site Cardiac Surgical Backup
Zoran Stajić, Zdravko M. Mijailović
171Pineal Region Tumors – Neurosurgical Review
Ivan Radovanovic, Kemal Dizdarevic, Nicolas de Tribolet, Tarik Masic, Sahib Muminagic
case reports
174Management of a Comatose Patient with Multiple Intracranial Aneurysms Lessons Learned
Kemal Dizdarevic, Vino Apok, Ibrahim Omerhodzic, Tarik Masic
books review
177Medical Informatics In A United And Healthy Europe
Contact Network and Satisfaction with Contacts in Children Whose Parents Have Post Traumatic Stress Disorder
Contact Network and Satisfaction with Contacts
in Children Whose Parents Have Post Traumatic
Stress Disorder
Zihnet Selimbasic1,3, Osman Sinanovic2,3, Esmina Avdibegovic1,3, Nemina Kravic1,3
Clinic for Psychiatry, University Clinical Center Tuzla, Bosnia and Herzegovina1
Clinic for Neurology, University Clinical Center Tuzla, Bosnia and Herzegovina2
Faculty of Medicine, University of Tuzla, Bosnia and Herzegovina3
Original paper
SUMMARY
Aim: The aim was to analyse contacts network and satisfaction with contacts among children of parents with
post traumatic stress disorder (PTSD). Subject and methods: The sample consisted of 100 pupils (age 10 to 15)
from two randomly chosen schools. Children were selected from general population, lived with both parents
who have had war traumatic experiences. They agreed to participate in psychometric research. We divided
them in two groups: observed (O) group of children (N=50) whose parents were showing symptoms of post
traumatic stress disorder (PTSD) and control (C) group of children (N=50) whose parents did not show symptoms of PTSD (evaluated by Harvard trauma questionnaire – BiH version). Contact network was examined
by a Map of Contact Network which includes contact and satisfaction with persons in close environment. In
relation to gender representatives of fathers and mothers, sample was homogenous. Results: The most important persons in children whose parents are showing symptoms of PTSD were schoolmates (88,0%), home
mate (86,0%), mother (72,0%), and father (2,0%). At children whose parents did not show symptoms of PTSD,
most important persons were schoolmate (94,0%), mother (80,0%), brother (6,0%), grandfather (8,0%), and
father (14, 0%). The most distinct disappointment in contacts in children with parents with PTSD symptoms
were family, relatives and friends, in school and formal contacts (p<0,001). Conclusion: Children of parents
who have had symptoms of post traumatic stress disorder (PTSD), the most important persons that they
communicate were schoolmates and they had problem in communicating with fathers and males. According
to satisfaction children whose parents suffered from PTSD were showing distinction in contacts with their
families, relatives, schoolmates and formal contacts.
Keywords: contact network, contact satisfaction, children, parents, post traumatic stress disorder
1. Introduction
War and post war period brings
many problems inside family, illness,
lower standard rate disruption in family contacts etc. There are different
circumstances that could disrupt traditional relationships and create confusion inside family. The development
of individual in social environment is
made of mutual interaction where external influence makes important factor in changes of development and it
emphasized unity between individual
and environment (1,2,3,4).
Environmental factors and individual factors influence on relationships
network through the life span (5). Parents, especially war veterans are usually overwhelmed by PTSD, what makes
them difficult to recognize as well as to
satisfy all family needs. The family represents basic spot and certain communication field which offer to any family
member aid in confrontation, built of
self esteem and self respect in facing
with critical moments (6). Preoccupied
with their war traumas, fears, anxiety
and guilty feelings parents with PTSD
became distant of family and for that
124
distance they accuse their family. Children are feeling unnoticed, detached
with adults, especially fathers. Parents’
usually sacrifice their authentic contact
with children and transfer it on appearance and cliché level rather to be floated
with unpleasant feelings (7). With traumatization, interactions between parents and children is destroyed (8,9).
2. aim
The aim of this study is to examine
contact network and satisfaction with it
in children whose parent’s show PTSD
symptoms.
3. Methods
In our examination we took 100
school age children (from 10 to 15
years old) from two randomly chosen
elementary schools from Tuzla Canton area. The research was approved
from Pedagogy and School Council of
Tuzla Canton, and school boards confirmed testing approach. The research
was done among children from 5. to 8.
grade. Based on social map of school
we took 150 children who have lived
in complete family. From that number
MED ARH 2009; 63(3) • ORIGINALNI ČLANCI / ORIGINAL PAPERS
we include 120 children whose parents
subscribe written approval for participating testing and fulfilled Harvard
Trauma Questionnaire. Among 120 of
children we discovered 50 whose parents have shown positive result in PTSD
in HTQ scale (> 2.5) and we have chosen 50 children whose parents have not
shown PTSD symptoms in HTQ scale
(< 2.5). Conditions for parents to participate in research were: general population, previous traumatic experiences,
show symptoms of posttraumatic
stress disorder, no other psychical disturbances. Conditions for children to
participate in research were: complete
family, equal number of male and female participants, elementary school
age (5-8 grade).
Harvard Trauma Manual, BosniaHerzegovina Version (HTQ) HTQ-Version for Bosnia and Herzegovina, consisted of four parts: possible traumatic
event, declaration for possible traumatic events, description of the most
traumatic event, questions about head
injuries, and questions about psychosocial disturbances caused by trauma. Results for PTSD and/or total score >2.5
is counted as „positive“for PTSD. Total
score value represent intensity of PTSD
and that result represent symptoms and
functional status.
Network contact map (10) is concerned to contact with persons who
surround child and his/her satisfaction
with those contacts. It measured contacts with the most important, important and les important persons, as well
as important persons with weak contacts and their satisfaction with those
contacts. Contacts are done in 1.) family, 2.) friends and neighbors, 3.) relatives, 4.) school, 5.) formal contacts.
For significance testing we have
used descriptive statistics. For performing of statistical evidences in research
we have used program SPSS 10.0 for
Windows.
4. Results
In total sample, participants age
11-13 represent 86.0% and there were
46.0% girls and 40.0% boys. (ME=12.06,
SDE=0.91 ), (MK=12.10, SDK=1.23) .
According to number of family members the most of them live in family with 4-5 members and there is no
statistically significant difference between groups (X2=6.27, df=4, p>0.05).
Regarding number of siblings children
Contact Network and Satisfaction with Contacts in Children Whose Parents Have Post Traumatic Stress Disorder
The most important persons
in contacts
Groups in sample
Children of parents Children of parents
with PTSD
without PTSD
N
%
N
%
44
88.0
47
94.0
43
86.0
43
86.0
36
72.0
40
80.0
30
60.0
33
66.0
21
42.0
29
58.0
7
14.0
4
8.0
6
12.0
3
6.0
5
10.0
4
8.0
1
2.0
7
14.0
2
4.0
6
12.0
Total
p
N%
School mate
91 91.0
0.940
Domicile friend
86 86.0
1.000
Mother
76 76.0
0.745
Doctor
63 63.0
0.789
Grandmother from mother
50 50.0
0.165
Aunt
11 11.0
0.518
Brother
9 9.0
0.473
Grandfather
9 9.0
0.813
Father
8 8.0
0.105
Grandmother from father
8 8.0
0.310
* Contacts network map.
Table 1. Distribution of participants according to contacts with the most important person and groups
in sample on Contact Nework Map.
Less important person in
contacts
Sister
Teacher of mother language
Brother
Family friend
Friend’s parents
Uncle
Principal
Aunt
Psychologist- pedagogue
Policeman
Groups in sample
Children of parents Children of parents
with PTSD
without PTSD
N
%
N
%
17
34.0
23
46.0
13
26.0
14
28.0
15
30.0
11
2.0
15
30.0
10
20.0
11
22.0
14
28.0
13
26.0
9
18.0
14
28.0
8
16.0
10
20.0
11
22.0
8
16.0
11
22.0
11
22.0
8
16.0
Total
N%
40 40.0
27 27.0
26 26.0
25 25.0
25 25.0
22 22.0
22 22.0
21 22.0
19 19.0
19 19.0
P
0.501
0.891
0.578
0.477
0.670
0.544
0.361
0.877
0.625
0.625
Table 2. Distribution of participants concerning contacts with less important persons and groups in
sample
of parents who shows symptoms of
PTSD live in family with more siblings
(X2=8.43, df=3, p<0.05) (p<0.05). According to contacts with the most important persons in total sample of children for 91.0% of them the most important person is school mate, domicile
friend 86%, 76% mother, and only 8.0%
children in total sample declare father
as the most important person in their
lives (Table 1).
Important persons in contacts are:
teacher (72.0%), father (70.0%), domicile friend (42.0%), nurse (38.0%) and
friend’s parents (30.0%). In group of
children whose parents did not show
symptoms of PTSD important persons are teacher (74.0%), father (72.0%),
nurse (42.0%), grandfather (40.0%) and
friend’s parents (38.0%). Results shows
that in group of children whose parents
show symptoms of PTSD less important
persons in contacts are sister (34.0%),
brother (30.0%), neighbor family friend
(30.0%), school principal (28.0%) and
uncle (26.0%). In group of children
whose parents did not show symptoms
of PTSD les important persons is sister (46.0%), teacher of mother language
(28.0%), friend’s parents (28.0%), aunt
(22.0%) and psychologist- pedagogue
Important persons,
but with weak
contacts
Children of parents
with PTSD
N
%
36
72.0
16
32.0
5
10.0
5
10.0
4
8.0
5
10.0
4
8.0
2
4.0
3
6.0
(22.0%). There was no statistically significant difference between children
from group whose parents show symptoms of PTSD and those whose parents do not show symptoms of PTSD
(Table 2).
Important persons with weak contacts are relatives (32.0%), aunts (10.0%),
school keeper (10.0%), family friend,
displaced persons (10.0%), father (8.0%)
and 72.0% of children have no answer.
In group of children whose parents do
not show symptoms of PTSD important persons with weak contacts were
relatives (24.0%), aunts (18.0%), school
keeper (16.0%), uncle (14.0%) and 84.0%
of children have no answer. Among
children of parents with PTSD symptoms and those children whose parents
did not show symptoms of PTSD there
was no statistically significant difference between groups (p>0.05). Important persons with weak contacts were
relatives (28.0%), aunt (14.0%), school
keeper (13.0%), family friend, displaced
persons (8.0%), father (5.0%) and 72.0%
have no answer (Table 3).
Regarding satisfaction with contacts
which make children of parents with
PTSD symptoms were more unsatisfied
with contacts which make with family,
relatives, school as well as formal contacts (p<0.001) (Table 4).
5. Discussion
Family system has significant influence on manifestation of PTSD symptoms and a person who suffers from
PTSD shows inappropriate emotional
reactions, withdrawal, social isolation
from other family members (Williams
and Williams, 1987; Sipprelle, 1994;
Grupe u uzorku
Children of parens
without PTSD
N
%
42
84.0
12
24.0
9
18.0
8
16.0
7
14.0
2
4.0
1
2.0
3
6.0
/
/
Total
P
N%
78 78.0
28 28.0
14 14.0
13 13.0
11 11.0
7 7.0
5 5.0
5 5.0
3 3.0
No answer
0.630
Relatives
0.592
Aunt
0.445
School keeper
0.553
Uncle
0.518
Family friend
0.411
Father
0.320
School principal
0.750
Medical doctor
0.157
Stepbrother/
3
6.0
/
/
3 3.0
0.157
stepssister
Table 3. Distribution of participants concerning contacts with important persons, but with weak
contacts and groups in sample.
MED ARH 2009; 63(3) • ORIGINALNI ČLANCI / ORIGINAL PAPERS
125
Contact Network and Satisfaction with Contacts in Children Whose Parents Have Post Traumatic Stress Disorder
Groups in sample
Children of parents with
Children of parents
Satisfaction with contacts
PTSD
without PTSD
N
%
N
%
35
70.0
50
100.0
Family s
15
30.0
/
/
35
70.0
50
100.0
Relatives s
15
30.0
/
/
38
76.0
48
96.0
Friends/neighbours s
12
24.0
2
4.0
35
70.0
49
98.0
School s
15
30.0
1
2.0
26
52.0
48
96.0
Formal contacts s
24
48.0
2
4.0
N=total number of children in group, s=satisfied, u=unsatisfied.
P
0.001
0.001
cording to satisfaction with contacts
they have, showed more unsatisfied in
contacts they made in family, relatives,
school, formal contacts.
REFERENCES
1.
0.001
0.001
0.001
2.
Table 4. Distribution of participants regarding satisfaction with contacts and groups in sample
Daud et al, 2008).
Our study has shown that in children whose parents suffer from PTSD
symptoms groups of school friends, domicile peers and mother represented
the most important persons and those
were appropriate with developmental
stage (2,15,16,17,18,19). Mother is still
the most important family member.
Very significant place presented mothers parents- grandmother and grandfather, what could be a part of cultural
milieu and relationships.
Some i mpor t a nt person s a re
teacher, father, medical professionals,
relatives and friends, but less important
persons are siblings. Boys from traumatized families had more difficulties
in communications with brothers and
male persons in family (p<0.05). There
was big percentage (78.0%) without any
answer what could mean that children
mostly communicate with persons in
their nearest surrounding.
Very weak contact was established
with father as family member and we
explain it with weak resonance and
weak capacity for communication because of father’s traumatic experiences in which made him emotionally
“stuck”, isolated and distanced, so children look confidence in communication with those persons who were capable to do that.
This point up that relations and
roles inside the family have been
changed, but it could also be consequence of specific developmental ageearly adolescence. Our results are
compliant with previous researches
(14,20,21,22,23) that the most important persons in the age of latency and
early adolescence are peers, parents,
126
school friends, teachers, siblings, cousins and close friends. It could be an “important social capital” for normal development and growing up. There were
no significant difference between two
groups in choosing the most important,
important and less important persons
with weak contacts (p>0.05), but children whose parents do not show PTSD
symptoms had more frequency in contacts with the most important persons.
Our study has shown that children
whose parents had PTSD symptoms
significantly more unsatisfied with contacts inside the family, relatives, school,
friends/ neighbors and formal contacts comparing with children whose
parents did not have PTSD symptoms
(p<0.001).
Our results are compatible with previous researches (7,9) which showed
that relationship between parents and
children were destroyed and that traumatised parents show up too little resonance for children. Many PTSD symptoms in parents are connected with interpersonal relationships like less interest for people and things around them,
weak emotional expression and irritability (20,24,25). Children are secondary traumatised and frustrated with
everyday contact forming, feels as detached and try find the way to get in
reached with family members (Guajarado, Snyder and Peterson , 2009).
6. Conclusion:
Children whose parents has PTSD
symptoms as the most important persons for communication picked up peer
friends, and had difficulties in communications with fathers and mail persons.
Children of parents with PTSD, ac-
MED ARH 2009; 63(3) • ORIGINALNI ČLANCI / ORIGINAL PAPERS
3.
4.
5.
6.
7.
8.
9.
10.
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MED ARH 2009; 63(3) • ORIGINALNI ČLANCI / ORIGINAL PAPERS
127
Etiološke karakteristike akutnih infekcija mokraćnog sistema stečenih u zajednici kod odraslih hospitaliziranih bolesnika
Etiološke karakteristike akutnih
infekcija mokraćnog sistema
stečenih u zajednici kod odraslih
hospitaliziranih bolesnika
Etiological Factors of Community Acquired Urinary Tract Infections
in Hospitalized Patients
Dilista Piljić¹, Sead Ahmetagić¹, Dragan Piljić², Muharem Zildžić³,Humera Porobić¹
Klinika za infektivne bolesti, Univerzitetski klinički centar Tuzla, Bosna i Hercegovina1
Klinika za kardiovaskularne bolesti, Univerzitetski klinički centar Tuzla, Bosna i Hercegovina2
Medicinski fakultet Univerziteta u Tuzli, Bosna i Hercegovina3
Originalni članak
SAŽETAK
Etiološki faktori infekcija mokraćnog sistema (IMS) stečenih u zajednici specifični su za životnu dob, spol, sezonu, kompliciranost i kategoriju infekcije, a njihova prevalenca i osjetljivost na antimikrobne lijekove pokazuju
geografsku varijabilnost i varijabilnost u vremenu. Uzimajući u obzir ove činjenice provedeno je istraživanje
kod 200 odraslih bolesnika sa akutnim IMS stečenim u zajednici, koji su zbog težine kliničke slike i neuspješnog
ambulantnog liječenja hospitalizirani u Klinici za infektivne bolesti Tuzla, u dvogodišnjem periodu (2006. i 2007.
godina). Dominantni etiološki faktori ovih infekcija su: E. coli (73,5%), Klebsiella spp. (8,5%), Proteus mirabilis
(5,5%), Pseudomonas aeruginosa (4%) i Enterococcus faecalis (3%). E. coli je značajno češći etiološki faktor IMS
kod žena, kompliciranog i nekompliciranog pijelonefritisa i cistouretritisa (P<0.0001). Nije nađena statistički
značajna razlika u učestalosti između etioloških faktora IMS u odnosu na dobne skupine bolesnika, godišnje
doba i prostatitis (P>0.05). E. coli je senzitivna na Cefalosporine III generacije, Gentamycin, Nitrofurantoin,
Norfloxacin, Ciprofloxacin i Pipemidinsku kiselinu (senzitivnost iznad 88,7%), Klebsiella spp. na Imipenem i
Meropenem (senzitivnost 100%), Proteus mirabilis na Imipenem i Meropenem (senzitivnost 100%) i relativno
na Amikacin (senzitivnost 81,8%), Pseudomonas aeruginosa na Imipenem (senzitivnost 100%) i Meropenem
(senzitivnost 87,5%) i Enterococcus faecalis na Vancomycin (senzitivnost 100%) i relativno na Ampicillin, Amoxicillin, Ciprofloksacin, Doxyciclin i Nitrofurantoin (senzitivnost 83,4%).
Ključne riječi: Etiološke karakteristike, IMS, osjetljivost.
Original paper
SUMMARY
Introduction: Etiological factors of community-acquired urinary tract infections (UTI) are specific for age,
gender, season, complication of UTI and type of UTI. Their prevalence and susceptibility to antimicrobial agents
shows geographic and time variability. Purpose: To evaluate etiological characteristics of acute communityacquired UTI in hospitalised patients. Patients and methods: This retrospective-prospective study included 200
adult patients with community-acquired UTI who were, in view of the serious clinical picture and unsuccessful
ambulatory treatment, hospitalised in the Clinic for Infectious Diseases in Tuzla, for a period of two years (2006
and 2007). The data concerning the age, gender, season, complication of UTI and type of UTI were collected
from the patient’s records. Urine analysis was done following standard microbiological methods, and the
antibiogram was done following standard disc-diffusion method on the Müeller-Hinton agar. Work results: The
dominant etiological factors of UTI were: E. coli (73.5%), Klebsiella spp. (8.5%), Proteus mirabilis (5.5%), Pseudomonas aeruginosa (4.5%) and Enterococcus faecalis (3%). The predominant etiological factor of this UTI was
E. coli (P<0.0001). E. coli was significantly more frequent etiological factor of UTI in females (P<0.0001). There
was no significant difference in the frequency between etiological factors of UTI for different age groups of
patients (P=0.173), or for different seasons (P>0.05). All etiological factors are significantly more frequent during warmer periods of the year (P<0.05). E. coli is a significantly more frequent etiological factor in complicated
and non-complicated pyelonephrytis and cystourethritis (P<0.05), but there was no significant difference of
frequency between etiological factors of prostatitis (P=0.7163). By analyzing the susceptibility for antimicrobials, we found that E. coli has good susceptibility for Cephalosporins of the third generation, for Gentamycin,
Nitrofurantoin, Norfloxacin, Ciprofloxacin and Pipemidin acid (susceptibility higher than 88.7%), Klebsiella spp.
for Imipenem and Meropenem (susceptibility 100%), Proteus mirabilis for Imipenem (susceptibility 100%) and
relatively for Amikacin (susceptibility 81.8%), Pseudomonas aeruginosa for Imipenem (susceptibility 100%)
and for Meropenem (susceptibility 87.5%) and Enterococcus faecalis for Vancomycin (susceptibility 100%) and
relatively for Ampicillin, Amoxicillin, Ciprofloxacin, Doxicyclin and Nitrofurantoin (susceptibility 83.4%). Conclusion: Etiological characteristics of UTI are specific for different regions. Evaluation of these characteristics in
our region is the basis for empirical antimicrobial therapy of UTI, which is necessary for a timely and successful
treatment of UTI.
Keywords: etiological characteristics, UTI, susceptibility
128
MED ARH 2009; 63(3) • ORIGINALNI ČLANCI / ORIGINAL PAPERS
1. UVOD
Etiološki faktori infekcija mokraćnog
sistema (IMS) stečenih u zajednici najčešće su G-negativne bakterije iz porodice
Enterobacteriaceae koje čine fiziološku
floru crijeva, a dobro rastu u mokraći. Escherichia coli (E. coli) je etiološki faktor
70-80% ovih infekcija (1). Kod nekompliciranih IMS, E. coli je etiološki faktor 5090% ovih infekcija (2,3), dok je kod kompliciranih IMS, E coli je, također, važan
etiološki faktor, ali se sa većom učestalošću javljaju i druge G-bakterije: Proteus
spp., Klebsiella spp., Enterobacter spp.,
Pseudomonas spp., Morganella spp., Citrobacter spp. i Acinetobacter spp. (2,4).
Od G+bakterija faktora, Staphylococcus
saprophyticus izaziva 5-15%, a u periodu
kasnog ljeta i rane jeseni i do 40% nekompliciranih IMS donjeg dijela mokraćnog
sistema kod mladih seksualno aktivnih
žena (2,5) i vodeći je etiološki faktor ovih
infekcija u SAD, Kanadi i skandinavskim
zemljama, dok je u nekim zemljama rijedak, samo 0,9% (6). Staphylococcus aureus je najčešći uzročnik intrarenalnog i
perinefritičkog apscesa (7), dok izolacija
Staphylococcus epidermidis u mokraći
najčešće predstavlja kontaminaciju mokraće, a samo rijetko može značiti IMS
vezanu za mokraćni katater. Enterococcus faecalis je češće povezan sa kompliciranim IMS, dok Streptococcus agalactiae često kolonizira genitalno područje i kontaminira mokraću, a rijetko
uzrokuje IMS (8). Candida albicans je
najčešći etiološki faktor gljivičnih IMS
kod bolesnika sa kamencima u mokraćnom sistemu, kod kateteriziranih bolesnika u jedinicama intenzivne njege i
kod pacijenata koji su dugo tretirani antimikrobnim lijekovima (9). Adenovirusi
su česti etiološki faktori hemoragičnog
cistitisa kod djece i primalaca alogenog
transplantata (7).
Dosadašnji rezultati istraživanja pokazuju da je prevalencija dominantnih
etioloških faktora IMS različita u odnosu
na spol i dob bolesnika, sezonu, kompliciranost i kategoriju IMS. Mikrobna
osjetljivost uzročnika IMS je smanjena
zbog povećane i često neracionalne upotrebe i povećanja antimikrobne rezistencije. Etiološki faktori IMS u odnosu na
navedene parametre pokazuju geografsku varijabilnost i varijabilnost u vremenu, te autori ističu potrebu kontinuirane evaluacije ovih faktora (3,10).
Etiološke karakteristike akutnih infekcija mokraćnog sistema stečenih u zajednici kod odraslih hospitaliziranih bolesnika
rentnim IMS i bolesnici
kod kojih nije urađen antibiogram. Analizirana
je učestalost etioloških
faktora IMS kod ovih
bolesnika u odnosu na
spol, životnu dob, godišnje doba, kompliciranost
3. PACIJENTI I METODE RADA
IMS i kategoriju IMS.
Retrospektivno-prospektivnim istra- Analizirana je osjetljiživanjem obuhvaćeno je 200 odraslih bo- vost dominantnih etilesnika sa akutnim IMS stečenim u za- oloških faktora IMS na
jednici, koji su zbog težine kliničke slike i antimikrobne lijekove. GRAFIKON 1. Dominantni etiološki faktori akutnih infekcija
mokraćnog sistema stečenih u zajednici kod hospitaliziranih bolesnika
neuspješnog ambulantnog liječenja hos- Svi podaci prikupljani
pitalizirani u Klinici za infektivne bole- su iz dostupnih historija
sti Tuzla u dvogodišnjem periodu (2006. bolesti. Urinokultura je rađena standar- 4. REZULTATI
i 2007. godina). Svim bolesnicima je po- dnim mikrobiološkim metodama, a anE. coli kao etiološki faktor akutnih
tvrđena IMS na osnovu kliničke slike, tibiogram standardnom disk-difuzio- IMS stečenih u zajednici registrirana je
laboratorijskih, radioloških, sonograf- nom metodom na Müeller-Hinton agaru kod 147 (73,5%) hospitaliziranih boleskih i endoskopskih pretraga, kod svih u Zavodu za mikrobiologiju UKC Tuzla. snika. Ne-E. coli etiološki faktori su reKorišten je program za statističku gistrirani kod 53 (26,5%) hospitalizirana
je dokazana signifikantna bakteriurija
(prema uputama Evropskog udruženja obradu podataka Arcus Quickstat Bio- bolesnika. E. coli je statistički značajno
urologa iz 2006. godine) ambulantno ili medical, Addison Wesley Longman Ltd, češći etiološki faktor IMS u odnosu na
do 48 sati od hospitalizacije i kod svih je 1997. Za testiranje statističke značajno- ne-E. coli etiološke faktore (P<0,0001).
urađen antibiogram. Iz istraživanja su sti razlike kvalitativnih podataka kori- Od ne-E. coli etioloških faktora, po učeisključeni bolesnici koji su uz IMS imali šten je test proporcija. Pri testiranju hi- stalosti su sljedeći: Klebsiella spp. 17
neku drugu akutnu infekciju, bolesnici sa poteza u svim proračunima je konzi- (8,5%), Proteus mirabilis 11 (5,5%), Pseintrahospitalno-stečenim IMS, bolesnici stentno pretpostavljen nivo značajnosti udomonas aeruginosa 8 (4%), Enterocosa genitalnim infekcijama, bolesnici sa od 5% (P=0.05).
ccus faecalis 6 (3%), Staphylococcus auasimptomatskom bakteriurijom i rekureus 3 (1,5%), Candida albicans i Salmonella enteritidis 2 (1%) i Streptococcus
Spol
agalactiae, Acinetobacter spp., EnteroŽenski spor
Muški spol
Ukupno
Etiološki faktori
bacter spp. i Mycobacterium tuberculon
%
n
%
n
%
sis 1 (0,5%) IMS. Računajući 95% interEscherichia coli
131
65,5
16
8,0
147
73,5 val povjerenja za proporciju oboljelih od
Klebsiella species
14
7,0
3
1,5
17
8,5 E. coli IMS (95%CI: 0.72-0.74), utvrđeno
Proteus mirabilis
9
4,5
2
1,0
11
5,5 je da je značajno veći broj bolesnika sa
Pseudomonas aeruginosa
4
2,0
4
2,0
8
4,0 E. coli IMS u odnosu na bolesnike sa neEnterococcus faecalis
3
1,5
3
1,5
6
3,0 E. coli IMS (P<0.0001). Dominantni etiOstali
10
5,0
1
0,5
11
5,5 ološki faktori ovih IMS prikazani su na
Ukupno
171
85,5
29
14,5
200
100,0 Grafikonu 1.
U odnosu na ukupan broj bolesnika
TABELA 1. Učestalost dominantnih etioloških faktora akutnih infekcija mokraćnog sistema stečenih u
200
(100%), registrirano je 131 (65,5%)
zajednici u odnosu na spol hospitaliziranih bolesnika
žena i 16 (8%) muškaraca sa E. coli IMS,
dok su infekcije sa ne-E. coli etiološkim
Dob (godine)
Etiološki
faktorima u znatno manjem broju: 14
15-24
25-34
35-44
45-54
55-64
≤65
Ukupno
faktori
(7%) žena i 3 (1,5%) muškarca sa IMS
(IMS)
n
%
n
%
n
%
n
%
n
%
n
%
n
%
uzrokovanim Klebsiellom spp., zatim 9
Escherichia
35 17,5
8 4,0 21 10,5
24 12,0 22 11,0 37 18,5 147 100,0 (4,5%) žena i 2 (1%) muškarca sa IMS
coli
uzrokovanim Proteus mirabilisom i daKlebsiella
4
2,0
2 1,0
1 0,5
3 1,5
3
1,5
4 2,0
17
8,5 lje 4 (2%) žene i muškarca sa IMS uzrospecies
kovanim Pseudomonas aeruginosom i 3
Proteus
2
1,0
1 0,5
0 0,0
2 1,0
0
0,0
6 3,0
11
5,5
mirabilis
(1,5%) muškarca i žene sa IMS uzrokovaPseudomonas
1
0,5
0 0,0
2 1,0
0 0,0
4
2,0
1 0,5
8
4,0 nim Enterococcus faecalisom. E. coli izaaeruginosa
ziva češće IMS kod žena uz značajnost
Enterococcus
1
0,5
0 0,0
1 0,5
0 0,0
2
1,0
2 1,0
6
3,0 razlike od P<0.0001. Računajući 95% infaecalis
terval povjerenja za proporciju žena sa E.
Ostali
2
1,0
0 0,0
2 1,0
2 1,0
2
1,0
3 1,5
11
5,5
coli IMS (95%CI: 0.72-0.74), utvrđeno je
Ukupno
45 22,5 11 5,5 27 13,5
31 15,5 33 16,5 53 26,5 200 100,0
da je u našem uzorku značajno veći broj
TABELA 2. Učestalost dominantnih etioloških faktora akutnih infekcija mokraćnog sistema stečenih u
žena sa E. coli IMS P<0.0001. Češće su
zajednici po dobnim skupinama hospitaliziranih bolesnika
žene sa Klebsiella spp. i Proteus mirabi2. CILJ ISTRAŽIVANJA
Cilj istraživanja je evaluacija etioloških karakteristika akutnih IMS stečenih u zajednici kod bolesnika hospitaliziranih u Klinici za infektivne bolesti
Tuzla u dvogodišnjem periodu (2006. i
2007. godina).
MED ARH 2009; 63(3) • ORIGINALNI ČLANCI / ORIGINAL PAPERS
129
Etiološke karakteristike akutnih infekcija mokraćnog sistema stečenih u zajednici kod odraslih hospitaliziranih bolesnika
lis IMS, ali statističku razliku nismo dokazivali zbog malog broja bolesnika sa
ovim infekcijama (tabela 1.).
E. coli kao etiološki faktor IMS registrirana je u najvećem broju u dobnoj
skupini 65 i više godina kod 37 (18,5%)
bolesnika, zatim u dobnoj skupini od
15-24 godine kod 35 (17,5%) bolesnika,
u dobnoj skupini 45-54 godine kod 24
(12%) bolesnika, u dobnoj skupini od
55-64 godine kod 22 (11%) bolesnika, u
dobnoj skupini od 35-44 godine kod 21
(10,5%) bolesnika i najmanje u dobnoj
skupini od 25-34 godine, kod 8 (4%) bolesnika. Ne-E. coli etiološki faktori IMS
u najvećem broju su registrirani u dobnoj skupini 65 i više godina kod 16 (8%)
bolesnika, zatim u dobnoj skupini od 5564 godine kod 11 (5,5%) bolesnika, u dobnoj skupini 15-24 godine kod 10 (5%) bolesnika, u dobnoj skupini 45-54 godine
kod 7 (3,5%) bolesnika, u dobnoj skupini
od 35-44 godine kod 6 (3%) bolesnika i
najmanje u dobnoj skupini od 25-34 godine kod 3 (1,5%) bolesnika. Ne postoji
statistički značajna razlika u učestalosti između E. coli i ne-E. coli etioloških
faktora IMS u navedenim dobnim skupinama bolesnika (P=0.173) (tabela 2.).
Rezultati istraživanja pokazuju da je
E. coli kao etiološki faktor IMS u najvećem broju registrirana u proljeće kod 56
(28%) bolesnika i ljeto kod 52 (26%) bolesnika, zatim u jesen kod 23 (11,5%) bolesnika i najmanje u zimskom periodu
kod 16 (8%) bolesnika. Učestalost E. coli
kao etiološkog faktora IMS u periodu
proljeće-ljeto kod 108 (54%) bolesnika
je statistički značajno veća od učestalosti u periodu jesen-zima kada je registrirana kod 39 (19,5%) bolesnika (P<0.0001).
Ne-E. coli etiološki faktori IMS, registrirani su u proljeće kod 16 (8%) bolesnika,
u ljeto kod 18 (9%) bolesnika, u jesen kod
Etiološki
faktori (IMS)
Escherichia
coli
Klebsiella
species
Proteus
mirabilis
Pseudomonas
aeruginosa
Enterococcus
faecalis
Ostali
Ukupno
Komplicirane IMS
Pyelonefritis Cistouretritis
n
%
n
%
Proljeće
Ljeto
Jesen
Zima
Ukupno
Etiološki
faktori (IMS) n
%
n
%
n
%
n
%
n
%
Escherichia
56
28,0
52 26,0
23 11,5
16
8,0 147
73,5
coli
Klebsiella
5
2,5
10
5,0
2
1,0
0
0,0
17
8,5
species
Proteus
2
1,0
3
1,5
4
2,0
2
1,0
11
5,5
mirabilis
Pseudomonas
2
1,0
2
1,0
4
2,0
0
0,0
8
4,0
aeruginosa
Enterococcus
2
1,0
1
0,5
2
1,0
1
0,5
6
3,0
faecalis
Ostali
5
2,5
2
1,0
4
2,0
0
0,0
11
5,5
Ukupno
72
36,5
70 35,0
39 19,5
19
9,5 200 100,0
TABELA 3. Učestalost dominantnih etioloških faktora akutnih infekcija mokraćnog sistema stečenih u
zajednici kod hospitaliziranih bolesnika po godišnjim dobima
Komplicirane IMS Nekomplicirane IMS
n
%
n
%
103
51,5
44
22,0
11
5,5
6
3,0
7
3,5
4
2,0
8
4,0
0
0,0
5
2,5
1
0,5
8
4,0
3
1,5
142
71,0
58
29,0
Etiološki faktori (IMS)
Escherichia coli
Klebsiella species
Proteus mirabilis
Pseudomonas aeruginosa
Enterococcu faecalis
Ostali
Ukupno
Ukupno
%
73,5
8,5
5,5
4,0
3,0
5,5
100,0
TABELA 4. Učestalost dominantnih etioloških faktora kompliciranih i nekompliciranih akutnih infekcija
mokraćnog sistema stečenih u zajednici kod hospitaliziranih bolesnika
16 (8%) bolesnika, dok su u zimskom periodu registrirani samo kod 3 (1,5%) bolesnika. Učestalost ne-E. coli etioloških
faktora IMS u periodu proljeće-ljeto kod
34 (17%) bolesnika je statistički značajno
veća od učestalosti u periodu jesen-zima
kada su registrirani kod 19 (9,5%) bolesnika (P=0.033) (tabela 3).
U odnosu na ukupan broj bolesnika
sa IMS, registrirano je 103 (51,5%) bolesnika sa kompliciranim IMS uzrokovanim E. coli, a 39 (19,5%) bolesnika sa
kompliciranim IMS uzrokovanim ne-E.
coli etiološkim faktorima. Registrirano je
44 (22%) bolesnika sa nekompliciranim
Nekomplicirane IMS
Prostatitis Pyelonephritis Cistouretritis
n
%
n
%
n
%
Ukupno
59
29,5
35
17,5
9
4,5
12
6,0
32
16,0
147
73,5
5
2,5
4
2,0
2
1,0
1
0,5
5
2,5
17
8,5
3
1,5
3
1,5
1
0,5
1
0,5
3
1,5
11
5,5
2
1,0
4
2,0
2
1,0
0
0,0
0
0,0
8
4,0
3
1,5
0
0,0
2
1,0
0
0,0
1
0,5
6
3,0
5
77
2,5
38,5
3
49
1,5
24,5
0
16
0,0
8,0
2
16
1,0
8,0
1
42
0,5
21,0
11
5,5
200 100,0
TABELA 5. Učestalost dominantnih etioloških faktora akutnih infekcija mokraćnog sistema stečenih u
zajednici prema kategoriji infekcije kod hospitaliziranih bolesnika
130
n
147
17
11
8
6
11
200
MED ARH 2009; 63(3) • ORIGINALNI ČLANCI / ORIGINAL PAPERS
IMS uzrokovanim E. coli, a 14 (7%) bolesnika sa nekompliciranim IMS uzrokovanim ne-E. coli uzročnicima. Ne-E. coli
etiološki faktori kompliciranih IMS su:
Klebsiella spp. kod 11 (5,5%), Pseudomonas aeruginosa kod 8 (4%), Proteus mirabilis kod 7 (3,5%), Enterococcus faecalis
kod 5 (2,5%) i ostali kod 8 (4%) bolesnika.
Ne-E. coli etiološki faktori u nekompliciranim IMS su: Klebsiella spp. kod 6 (3%),
Proteus mirabilis kod 4 (2%), Enterococcus faecalis kod 1 (0,5%) i ostali kod 3
(1,5%) bolesnika. Računajući 95% interval povjerenja za proporciju kompliciranih IMS (95%CI: 0.71-0.73) i nekompliciranih IMS (95%CI: 0.71-0.77) izazvanih
E. coli, utvrđeno je da su proporcije ovih
IMS značajno češće nego proporcije istih
IMS izazvanih ne-E. coli etiološkim faktorima. U svim slučajevima proračuna je
P<0.05 (tabela 4).
U odnosu na ukupan broj bolesnika
sa IMS, E. coli je etiološki faktor kompliciranog pijelonefritisa kod 59 (29,5%)
bolesnika, kompliciranog cistouretritisa kod 35 (17,5%) bolesnika, prostatitisa kod 9 (4,5%) bolesnika, nekompliciranog pijelonefritisa kod 12 (6%) bolesnika i nekompliciranog cistouretritisa
kod 32 (16%) bolesnika, a ne-E. coli etiološki faktori kompliciranog pijelonefritisa kod 18 (9%) bolesnika, komplicira-
Etiološke karakteristike akutnih infekcija mokraćnog sistema stečenih u zajednici kod odraslih hospitaliziranih bolesnika
nog cistouretitisa kod 14 (7%) bolesnika,
prostatitisa kod 7 (3,5%) bolesnika, nekompliciranog pijelonefritisa kod 4 (2%)
bolesnika i nekompliciranog cistouretritisa kod 10 (5%) bolesnika. Proporcija slučajeva kompliciranog i nekompliciranog pijelonefritisa i cistouretritisa izazvanim E. coli značajno je veća
od proporcije slučajeva istih izazvanim
ne-E. coli etiološkim faktorima. U svim
slučajevima proračuna je P<0.05. Ne
postoji statistički značajna razlika proporcija slučajeva prostatitisa izazvanog
E. coli i ne-E. coli etiološkim faktorima
(P=0.7163) (tabela 5.).
Analizom senzitivnosti dominantnih
etioloških faktora IMS na antimikrobna
sredstva evidentno je da je E. coli dobro
osjetljiva na Cefalosporine III generacije,
Gentamycin, Nitrofurantoin, Norfloxacin, Ciprofloxacin i Pipemidinsku kiselinu (senzitivnost iznad 88,7%). Klebsiella spp. je dobro osjetljiva na Imipenem
i Meropenem (senzitivnost 100%), Proteus mirabilis na Imipenem i Meropenem (senzitivnost 100%) i relativno na
Amikacin (81,8%), Pseudomonas aeruginosa na Imipenem (senzitivnost 100%) i
Meropenem (87,5%) i Enterococcus faecalis na Vancomycin (senzitivnost 100%)
i relativno na Ampicillin, Amoxicillin,
Ciprofloksacin, Doxyciclin i Nitrofurantoin (senzitivnost 83,4 %) (tabela 6.).
5. DISKUSIJA
Od ukupno 200 hospitaliziranih bolesnika sa akutnim IMS stečenim u zajednici, 73,5% bolesnika imalo je E. coli-IMS što je čini predominantnim etiološkim faktorom IMS (P<0.0001). Sljedeći etiološki faktori po učestalosti su:
Klebsiella spp., Proteus mirabilis, Pseudomonas aeruginosa i Enterococcus faecalis, što je saglasno sa rezultatima istraživanja drugih istraživača (3). E. coli značajno češće uzrokuje IMS kod žena, 131
(65,5%) u odnosu na muškarce, 16 (8%),
(P<0.0001). Prema podacima iz dostupne literature kod muškaraca su akutne
IMS, naročito akutni prostatitis najčešće
uzrokovane E. coli, a zatim slijede Klebsiella pneumoniae, Morganella spp. i
Enterococcus spp. (11).
U odnosu na životnu dob bolesnika
ne postoji značajna razlika u učestalosti
E. coli i ne-E. coli etioloških faktora IMS
(P=0.173). Svi uzročnici su značajno češći u starijoj životnoj dobi, 65 i više godina (P<0.05). Prema Petersonu, kod bolesnika starije životne dobi koji boluju od
hroničnih i degenerativnih bolesti i kod
Antimikrobni
lijek
Ampicillin
Amoxicillin
Amoxiclav
Piperacillin
Norfloxacin
Ciprofloxacin
Imipenem
Meropenem
Vancomycin
Cefotaxim
Ceftriaxon
Ceftazidim
Erythromycin
Doxycyclin
Gentamycin
Amikacin
Tmp-Smx
Nitrofurantoin
Pipemid. kis.
Escherichia
coli
Klebsiella
species
%S
43,3
46,5
43,4
*
92,4
88,7
*
*
*
95,5
95,2
95,9
*
*
94,6
*
66,5
92,5
90,5
%S
21,8
35,3
35,3
*
41,2
*
100,0
100,0
*
*
64,7
53,0
*
*
41,2
64,7
47,0
17,7
17,7
Proteus Pseudomonas
mirabilis
aeruginosa
%S
18,2
45,5
45,5
*
54,5
45,5
100,0
100,0
*
*
36,4
27,3
*
*
54,5
81,8
*
18,2
27,3
Enterococcus
faecalis
%S
*
*
*
74,1
25,0
37,5
100,0
87,5
*
*
12,5
*
*
*
25,0
37,5
*
*
*
%S
83,4
83,4
66,7
*
66,7
83,4
*
*
100,0
*
*
*
66,7
83,4
66,7
*
33,3
83,4
*
TABELA 6. Osjetljivost na antimikrobne lijekove dominantnih etioloških faktora akutnih infekcija
mokraćnog sistema stečenih u zajednici kod hospitaliziranih bolesnika. S–senzitivan, *–nije rađen
antibiogram, Tpm-Smx–trimetoprim-sulphametoxasol, Pipemid. kis.–pipemidinska kiselina
kojih su često primijenjene agresivne terapijske i dijagnostičke procedure na mokraćnom sistemu, uzročnici IMS sem E.
coli su često i druge enterobakterije što je
u skladu sa faktorima rizika i spektrom
etioloških faktora za komplicirane IMS
(12), dok se Staphylococcus saprophyticus češće javlja kod mladih seksualno aktivnih žena (2,5).
Analizirajući učestalost etioloških
faktora u odnosu na godišnje doba, dobili smo zanimljive rezultate da su i E.
coli (P<0.0001) i ne-E. coli etiološki faktori (P=0.033) značajno češći u toplijem
dijelu godine (proljeće–ljeto) što daje
IMS epitet sezonskih bolesti. Dosadašnje
studije pokazuju da su IMS nešto češće u
hladnijim godišnjim dobima, dok Staphylococcus saprophyticis češće uzrokuje
IMS u kasno ljeto i ranu jesen 5-15%, pa
čak i do 40% IMS (5).
E. coli je značajno češće etiološki faktor kompliciranih i nekompliciranih IMS
u odnosu na ne-E. coli etiološke faktore
(P<0.0001), što se također slaže sa izvještajima drugih istraživača koji naglašavaju učestalost E. coli u kompliciranim
i nekompliciranim IMS (2,4), s tim što
su češće uzročnici kompliciranih IMS
i druge G-bakterije (2,3,4). Istraživanje
provedeno u Izraelu dalo je rezultate da
je prevalenca E. coli kao uzročnika IMS
u padu od 70,5% u 1991. godini, na 56%
u 2000. godini, što potvrđuje varijabilnost prevalence etioloških faktora (E.
coli) u vremenu (3).
U odnosu na kategoriju IMS E. coli je
značajno češći etiološki faktor kompliciranog i nekompliciranog cistouretritisa
i pijelonefritisa (P<0.05), dok kod bolesnika sa prostatitisom nema značajne razlike u učestalosti E. coli i ne-E. coli etioloških faktora (P=0.7163). Alos izvještava da je E. coli etiološki faktor 85%
nekompliciranog cistitisa, dok su Staphylococcus saprophyticus, Proteus mirabilis, Streptococcus agalactiae i Klebsiella spp. odgovorni za većinu drugih slučajeva (10). Colodner i sar. izvještavaju
da je u Izraelu svega 0,9% nekompliciranih IMS uzrokovano sa Staphylococcus
saprophyticus (6).
6. ZAKLJUČCI
Dominantni etiološki faktori akutnih IMS stečenih u zajednici kod hospitaliziranih bolesnika su: E. coli (73,5%),
Klebsiella spp. (8,5%), Proteus mirabilis
(5,5%), Pseudomonas aeruginosa (4%) i
Enterococcus faecalis (3%). E. coli je značajno češći etiološki faktor IMS kod žena,
kompliciranog i nekompliciranog pijelonefritisa i cistouretritisa (P<0.0001). Nije
nađena značajna razlika u učestalosti između etioloških faktora IMS u odnosu
na dobne skupine bolesnika, godišnje
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131
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European Association
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Mikroalbuminurija i ultrazvučne karakteristike bubrega u djece i adolescenata sa Dijabetes melitusom tip 1
Mikroalbuminurija i ultrazvučne
karakteristike bubrega u djece
i adolescenata sa Dijabetes
melitusom tip 1
Microalbuminuria and Ultrasound Characteristics of Kidneys in
Children and Adolescents with Diabetes Mellitus Type 1
Evlijana Hasanović1, Denijal Tulumović2, Goran Imamović2, Senaid Trnačević2
Klinika za dječije bolesti, Univerzitetski klinički centar, Tuzla, Bosna i Hercegovina1
Klinika za interne bolesti, Univerzitetski klinički centar, Tuzla, Bosna i Hercegovina2
Originalni članak
Sažetak
Cilj rada je bio utvrditi ultrazvučnim pregledom dimenzije i volumen bubrega u djece i adolescenta sa dijabetes
melitusom tip 1 (DMT1), te ih uporediti sa nalazom mikroalbuminurije, metaboličkom kontrolom bolesti i
vrijednostima klirens kreatinina. U 80. djece i adolescenata, koji su oboljeli od DMT1 u dobi od 2. do 16. godine
života, morfometrijski ultrazvukom mjerila su se oba bubrega. Nefelometrijskom metodom se je iz tri uzastopna uzorka urina određivala mikroalbuminurija. Određivan je serumski kreatinin u ispitanika sa mikroalbuminurijom. Demografski podaci su dobiveni odgovorom od roditelja i iz medicinske dokumentacije ispitanika. U
odnosu na dužinu trajanja bolesti svi ispitanici su podijeljeni u dvije grupe: prva grupa sa trajanjem DMT1 <10
godina i druga sa trajanjem bolesti >10 godina. U ispitanika sa trajanjem DMT1 duže od 10 godina učestalost
patološkog nalaza uzdužnog dijametra i volumena oba bubrega u odnosu na dob i antropometrijske standarde
je statistički značajno veća. Također, isti ispitanici imali su statistički značajno veću srednju vrijednost HbAlc i
učestalije mikroalbuminuriju. Kod ispitanika sa mikroalbuminurijom ukupna srednja vrijednost klirensa kreatinina bila je u granicama referentnih vrijednosti a statistički značajno veća kod ispitanika kod kojih je bolest
trajala manje od deset godina, što govori u prilog hiperfiltracije bubrega. Ultrazvučno praćenje dimenzija i
volumena bubrega uz mikroalbuminuriju, može ukazati na postojanje ranih faza dijabetesne nefropatije (DN) i
uticati na njeno sprečavanje i dalju progresiju.
Ključne riječi: dijabetes melitus, nefropatija, mikroalbuminurija, ultrazvučni parametri.
Original paper
SUMMARY
The aim of the study was to compare ultrasound findings of kidneys in children and adolescents with diabetes
mellitus type 1 (DMT1), establish the association with microalbuminuria, blood pressure values and metabolic
control of the disease, and creatinine clearance. In 80 children and adolescents with DMT1, in whom illness
occurred in period between 2 and 16 years of age, morphometry measurements with ultrasound were
performed. Nephelometric method of three consecutive samples of urine determined microalbuminuria. In
patients with microalbuminuria, creatinine clearance was also measured. Demographic data were obtained
from the parents and from the patients medical records. In relation to the duration of the disease, all patients
were divided into two groups: the first group of patients with illness lasting for less than 10 years, and the
second were those whose illness had lasted more than 10 years. In patients with duration of DMT1 of more
than 10 years, the frequency of pathological findings of the longitudinal diameter and volume of both kidneys
in relation to age and anthropometric standards was statistically significantly greater. Also, the finding of
microalbuminuria was more frequent. In the group of patients with DMT1 lasting for more than 10 years, the
mean value of HBAlc was statistically significantly higher. In patients with microalbuminuria the total mean
value of creatinine clearance was within the bounds of the reference values and was statistically significantly
higher in patients in whom the illness had lasted less than three years, which indicates hyperfiltration of the
kidneys. Alongside microalbuminuria, monitoring of the dimension and volume of the kidneys may indicate
the existence of the early phases of diabetic nephropathy and result in its prevention and prevention of illness
progression.
Keywords: Diabetes mellitus, nephropathy, microalbuminuria, ultrasound parameters
1. UVOD
Dijabetesna nefropatija (DN) je najčešća specifična dugoročna komplikacija
dijabetes melitusa tip 1 (DMT1). Kod 2080% oboljele djece i adolescenata u kasnijoj životnoj dobi razviti će se dijabetesna nefropatija (1, 2). Progresivno propadanje funkcije bubrega u DMT1 prvi
su opisali Mogensen i sar., (3). Nezavisno jedan od drugoga nekoliko je autora otkrilo da postoje tri faze DN: hipertrofijska hiperfiltracija, mikroalbuminurija i hronično zatajenje bubrega (4,
5). Teško je tačno odrediti kada počinje
proces oštećenja bubrega (6). Bubrežna
disfunkcija se javlja češće kada je bolest
počela prije 20. godine života. Jedini prvi
znak nefropatije je pojava mikroalbuminurije (7, 8, 9). Nerijetko mikroalbuminurija prelazi u makroalbuminuriju, dolazi do pada glomerularne filtracije i porasta krvnog pritiska (10).
U početnim stadijima dijabetesne
nefropatije u djece sa normalnom bubrežnom funkcijom ultrazvučni pregled
može biti od pomoći pri detekciji ranih
patomorfoloških parenhimskih lezija
bubrega (11).
Ultrasonografija kao jedna od screening metoda, svakim danom ima sve
veću ulogu u praćenju bolesti urinarnog trakta u djece. Ultrazvučna aparatura je široko dostupna, pregled jednostavan, relativno brz i ne zahtijeva posebnu pripremu pacijenta. Za preciznu
evaluaciju abnormalnosti morfologije
bubrega, a indirektno za kliničke manifestacije i funkciju potrebno je poznavanje normalnih sonografskih parametara bubrega djece (12).
2. CILJ RADA
Obzirom da mikroalbuminurija uz
praćenje ultrazvučnim pregledom dimenzija i volumena bubrega predstavljaju značajne parametre u kliničkoj
procjeni nastanka DN, poduzeto je ovo
istraživanje, s ciljem da se utvrdi korelacija nalaza mikroalbuminurije i ultrazvučnog pregleda bubrega, kao jednostavne i rutinske metode, u djece i adolescenata sa DMT1, te da bi se moglo koristiti u blagovremenom otkrivanju, liječenju i prevenciji DN.
3. METODE I ISPITANICI
Analizom je obuhvaćeno 80 ispitanika, oba spola, različite životne dobi
koji se redovno kontrolišu u ambulanti
za endokrinologiju Klinike za dječije bolesti Univerzitetsko kliničkog centra Tuzla (UKC Tuzla).
Kriteriji uključenja u ovu studiju su
bili da je kod ispitanika DMT1 počeo u
uzrastu od 2. do 16. godine života i da u
terapiji primaju insulin. Dok su kriteriji
isključenja iz ove studije predstavljali pojavu akutne i hronične bolesti (centralnog, respiratornog, kardiovaskularnog,
gastrointestinalnog, genitourinarnog sistema), sistemska oboljenja (lupus eritematodes, juvenilni reumatoidni artritis,
dijabetes melitus tip 2), oboljenja jetre,
trudnoća i upotreba lijekova kao što su
kortikosteroidi duži vremenski period.
U odnosu na dužinu trajanja bolesti
svi ispitanici su podijeljeni u dvije grupe:
prvu kod kojih je bolest trajala manje
od deset godina i drugu kod kojih je bolest trajala više od deset godina. U odnosu na životnu dob kada je počeo dijabetes, ispitanici su također podijeljeni u
tri podgrupe: prvu grupu sačinjavali su
ispitanici koji su u vrijeme oboljevanja
od DMT1 imali manje od 4.9 godina,
drugu grupu ispitanici od 5 do 10.9 godina i treću podgrupu ispitanici stariji
od 11 godina.
Prije dolaska na pregled, svaki ispi-
MED ARH 2009; 63(3) • ORIGINALNI ČLANCI / ORIGINAL PAPERS
133
Mikroalbuminurija i ultrazvučne karakteristike bubrega u djece i adolescenata sa Dijabetes melitusom tip 1
tanik uzeo je u dva prethodna dana tri
uzorka urina, dva u jutarnjim i jedan u
poslijepodnevnim satima. Do dolaska
na pregled uzorci su čuvani u frižideru
na temperaturi između +2 do +8°C (13).
U nativnom urinu određivana je mikroalbuminurija nefelometrijskom metodom sa reagensima firme Dade Behring
(13). Za perzistentnu mikroalbuminuriju smatrane su vrijednosti albumina
20-200 µg/minuti u najmanje dva od tri
uzastopna uzorka urina, a intermitentnu
ako su vrijednosti albumina bile 20-200
µg/minuti u jednom od tri uzastopna
uzorka urina (14).
Metabolička kontrola bolesti procjenjivana je na osnovu prosječnih vrijednosti svih dostupnih nalaza HbAlc od
početka bolesti do dana ispitivanja.
Dužina trajanja bolesti izračunata je
u decimalnim godinama na osnovu datuma početka bolesti i datuma skupljenog trećeg uzorka urina. Za datum početka bolesti smatrao se datum primanja prve injekcije insulina (15).
Za određivanje funkcionalnog stanja bubrega određivan je klirens endogenog kreatinina pomoću Schwartzova
jednadžbe a na osnovu Counahan- Barratova jednadžbe izračunata je i procjenivanja glomerularna filtracija (GF) (16,
17). Nije bilo moguće kontrolisati GF kod
zdrave djece i adolescenata.
Kod svih ispitanika pomoću »Realtime« ultrazvučnog pregleda radila su
se morfometrijska mjerenja oba bubrega.
Real- time tehnikom na aparatima Toshiba Corevision 350 i Logiq 3 uz upotrebu multifrekventne konveksne sonde
od 3.75 mHz, prvo u ležećem položaju
na leđima, te u desnom i lijevom „polukosom dekubitus- položaju“ mjerile su
se dimenzije oba bubrega pojedinačno,
maksimalni uzdužni promjer bubrega,
širina (izražene u mm), izgled parenhima
(ehogenost), pratio izgled sinusa i određivao volumen bubrega u mililitrima
(ml). Analizirane su dimenzije bubrega
dobivene iz maksimalnog uzdužnog tzv.
centralnog srednjeg najdužeg dijametra
bubrega. Širina parenhima je mjerena
iz prethodnog presjeka na mjestu spoja
srednje i spolje trećine (12, 18, 19, 20).
Za ovo istraživanje dobijena je saglasnost Etičkog komiteta UKC u Tuzli.
Statistička obrada podataka
Za testiranje statističkih značajnosti razlike među uzorcima korišteni su
X²-test, Studentov t-test i Z-test proporcija). Razlika među uzorcima smatrala se značajnom ako je P< 0.05. U sta134
tističkoj obradi podataka je korišten Ar- perzistentnu.
cus QuickStat program (21).
Klirens kreatinina u ispitanika sa mikroalbuminurijom izračunat na osnovu
4. REZULTATI RADA
Schwartzove i Counahan Barrattove jedU Tabeli 1 prikazane su demograf- nadžbe prikazan je u Tabeli 4.
ske karakteristike ispitanika u odnosu
Ukupna srednja vrijednost klirensa
na dob početka DMT1.
kreatinina kod ispitanika sa mikroalbuminurijom bila
Dob početka
Demografske
je u granicama refešećerne bolesti tip 1 (godine)
Ukupno
karakteristike
rentnih vrijednosti
<4.9
5-10.9
>11
Broj (sa MA**)
9
10
19 i iznosla je 83.9±5.1.
Broj (bez MA)
19
24
18
61 Srednja vrijednost
M/Ž (sa MA)
3/6
5/5
8/11 klirensa kreatinina
M/Ž (bez MA)
14/5
13/11
12/6
39/22 iznosila je 87.5±5.5
Dob u vrijeme ispitivanja
u 6 (31.5%) ispita(godine; ±SD) (sa MA)
- 17.2±5.1 19.5±6.2
18.4±5.6
nika, kod kojih je
Dob u vrijeme ispitivanja
9.9±3.8 14.1±3.6 19.4±4.7
14.4±4.7
DMT1 trajao ma(godine; ±SD) (bez MA)
nje od 10 godine, a
Dob početka bolesti
(godine; ±SD) (sa MA)
8.5±1.9 11.9±0.8
10.3±2.2 u 13 (68.5%) ispitaDob početka bolesti
3.3±1.9
8.7±1.8 12.8±1.3
8.3±1.7 nika sa dužim tra(godine; ±SD) (bez MA)
janjem DMT1 je
Trajanje dijabetesa (godine;
bio 80.4±4.5. Sta±SD) (sa MA)
8.6±6.7 6.5±5.9
7.5±6.2
Trajanje dijabetesa
6.8±3.7
5.2±3.6 6.7±4.8
6.3±1.9 tistički značajno
veća ukupna sred(godine; ±SD) (bez MA)
nja vrijednost kliHbA1C (%; ±SD) (sa MA)
9.4±2.9 8.9±1.0
9.2±2.1
HbA1C (%; ±SD)
8.2±1.2
8.6±1.7 8.2±1.6
8.3±1.3 rensa kreatinina
(bez MA)
bila je kod ispitaTabela 1. Demografske karakteristike ispitanika u odnosu na dob početka
nika kod kojih je
DMT1*, * Diabetes mellitus tip 1, ** Mikroalbuminurija
bolest trajala manje od deset godina
Najveći broj ispitanika (41.5%) u vri- u odnosu na ispitanike kod kojih je bojeme početka bolesti bio je u dobu od lest trajala duže. Međutim, nije bilo sta5 do 10.9 godina. Dječaci oboljeli od tistički značajne razlike između vrijedDMT1 u svim dobnim skupinama bili nosti klirenska kreatinina kod ispitanika
su češće zastupljeni u odnosu na djevoj- sa intermitentnom i perzistentnom mičice. Prosječna dob početka bolesti uku- kroalbuminurijom u odnosu na dužinu
pno gledano iznosila je 8.6±3.7 godina trajanja bolesti.
a prosječne vrijednosti
Trajanje DMT1
HbAlc za sve ispitanike
Ukupno
Mikroaliznosile su 8.3±1.7%.
< 10 godine
>10 godine
buminurija
Učestalost intermin
%
n
%
n
%
tentne i perzistentne miIntermitentna
5
26.3
3 15.8
8 42.1
kroalbuminurije u odPerzistentna
6
31.6
5 26.3
11 57.9
nosu na trajanje DMT1
Ukupno
11
57.9
8 42.1
19 100.
(<10 i >10 godina) prikaTabela 2. Učestalost intermitentne i perzistentne mikroalbuminurije u
zana je u Tabeli 2.
U grupi sa trajanjem odnosu na trajanje DMT1 (<10 i >10 godina)
DMT1 manje od 10 godina, 11 ili 57.9% ispiKlirens kreatinina (ml/min;
±SD)
Ukupno
tanika imalo je mikro- Mikroal(n=19)
< 10 godine
>10 godine
albuminuriju, a od toga buminurija
(n=6)
(n= 13)
broja u 5 ispitanika mikroalbuminurija je bila Intermitentna
83.6±9.6A
77.2±15.5 80.4±12.1
intermitentna, a u 6 per- (n= 8)
zistentna. U grupi ispita- Perzistentna
91.4±17.1B
83.5±14.6 85.6±14.8
nika sa trajanjem DMT1 (n=11)
87.5±5.5C
80.4±4.5 83.9±5.1
duže od 10 godina 8 Ukupno (n=19)
(42.1%) ispitanika imalo Tabela 4 Klirens kreatinina u ispitanika sa mikroalbuminurijom u
je izraženu mikroalbu- odnosu na dužinu trajanja DMT. At = 0.92; df = 17; P = 0.37, Bt =
minuriju, i to 3 ispita- 1.04; df = 17; P = 0.31, Ct = 2.08 df = 17; P = 0.008 u odnosu na
nika intermitentnu, a 5 ispitanike sa trajanjem DMT1 više od 3 godine.
MED ARH 2009; 63(3) • ORIGINALNI ČLANCI / ORIGINAL PAPERS
Mikroalbuminurija i ultrazvučne karakteristike bubrega u djece i adolescenata sa Dijabetes melitusom tip 1
t r aja njem DMT1 kojih je DMT1 trajao duže od 10 godina
od 10 godina u od- u odnosu na ispitanike kod kojih je boDecimalna dob i
nosu na decimalnu lest kraće trajala. Razlozi pojave mikroantropometrijski
Nalaz UZ
Nalaz UZ
dob t a kođer n ije albuminurije u naših ispitanika usko su
parametri
Normalan
Patološki
Normalan
Patološki
statistički značajna, povezani sa njihovom slabom dugogoN; (%)
N; (%)
N; (%)
N; (%)
dok u odnosu na tje- dišnjom metaboličkom kontrolom boDob
58 (93.4)
4 (6.6)
16 (88.8)
2 (11.2)A lesnu visinu, težinu lesti na što ukazuju i njihove prosječne
Tjelesnu visinu
57 (91.9)
5 (8.1)
14 (77.7)
4 (22.3)B i površinu postoji srednje vrijednosti HbAlC od 9.2±2.1%.
Tjelesnu masu
56 (90)
6 (10)
14 (77.7)
4 (22.3)C statistički značajna Tome u prilog govori i nalaz HbAlc od
Tjelesnu površinu
55 (88.7)
7 (11.3)
14 (77.7)
4 (22.3)D razlika.
8.3±1.2% u naših ispitanika bez mikroU
Tabeli
7
prikaalbuminurije.
Tabela 5. Učestalost normalnog i patološkog nalaza uzdužnog dijametra
zana je, u odnosu na
U naših ispitanika sa mikroalbumidesnog bubrega u odnosu na trajanje DMT1 mjerenog ultrazvukom i
izračunatog u odnosu na decimalnu dob i antropometrijske parametre.
trajanje bolesti uče- nurijom ukupna srednja vrijednost kliAZ = 0.11; 95% CI 0.013751 – 0.347121; P = 0.11, BZ = 0.22; 95%
stalost normalnog rensa kreatinina bila je u granicama reCI 0.064092 – 0.476373; P = 0.02, CZ = 0.55; 95% CI 0.307572 –
i patološkog nalaza ferentnih vrijednosti i iznosila je 83.9±5.1
0.784699; P = 0.41, DZ = 1.45; 95% CI 0.357451 – 0.827014; P = 0.01
volumena desnog ml/min. Značajno veća ukupna srednja
u odnosu na ispitanike sa trajanjem DMT1 manje od 10 godina.
bubrega mjerenog vrijednost klirensa kreatinina, iako u
ultrazvukom i izra- granicama normalnih vrijednosti, bila
Učestalost normalnog i patološkog
čunatog u odnosu na decimalnu dob i je u ispitanika kod kojih je bolest tranalaza uzdužnog dijametra desnog buantropometrijske parametre.
jala manje od deset godina. Te veće vribrega, mjerenog ultrazvukom i izračuUčestalost patolonatog u odnosu na decimalnu dob i anUltrazvučni nalaz uzdužnog dijametra lijevog
škog nalaza volumen
tropometrijske parametre a s obzirom na
bubrega u odnosu na trajanje DMT1
desnog bubrega u grupi
trajanje bolesti prikazana je u Tabeli 5.
Decimalna
dob
i
<10
godina (n=62) >10 godina (n=18)
ispitanika sa trajanU grupi ispitanika sa trajanjem
antropometrijski
Nalaz UZ
Nalaz UZ
jem DMT1 duže od
parametri
DMT1 duže od 10 godina, učestalost pa10 godina u odnosu
Normalan
Patološki
Normalan
Patološki
tološkog nalaza uzdužnog dijametra dena decimalnu dob i
N; (%)
N; (%)
N; (%)
N; (%)
snog bubrega je statistički značajno veća
tjelesnu visinu stati- Dob
58
(93.5)
4
(6.5)
16
(88.8)
2
(11.2)A
prema tjelesnoj visini i površini u odnosu
stički se značajno ne Tjelesnu visinu
57 (91.9)
5 (8.1) 14 (77.7) 4 (22.3)B
na ispitanike sa trajanjem DMT1 manje
razlikuju, dok prema
Tjelesnu masu
56 (90)
6 (10) 14 (77.7) 4 (22.3)C
od 10 godina.
tjelesnoj težini i povTjelesnu
površinu
56
(90)
6 (10) 14 (77.7) 4 (22.3)D
U Tabeli 6 prikazana je učestalost
ršini postoji statistički
normalnog i patološkog nalaza uzdužTabela 6. Učestalost normalnog i patološkog nalaza uzdužnog dijametra
značajna razlika.
nog dijametra lijevog bubrega, mjerenog
lijevog bubrega u odnosu na trajanje DMT1 mjerenog ultrazvukom i
Učestalost normalizračunatog u odnosu na decimalnu dob i antropometrijske parametre.
ultrazvukom i izračunatog u odnosu na
nog i patološkog na- AZ = 0.33; 95% CI 0.133427 – 0.590075; P = 0.12, BZ = 2.06; 95%
decimalnu dob i antropometrijske palaza volumena lijevog CI 0.260191 – 0.739809; P = 0.02, CZ = 2.06; 95% CI 0.307572 –
rametre s obzirom na trajanje bolesti.
bubrega mjerenog ul- 0.784699; P = 0.02, DZ = 3.74; 95% CI 0.260191 – 0.739809; P =
Učestalost patološkog nalaza uzdužtrazvukom i izračuna- 0.0002 u odnosu na ispitanike sa trajanjem DMT1 manje od 10 godina.
nog dijametra lijevog bubrega u ispitatog u odnosu na decinika sa trajanjem DMT1 manje od 10 gomalnu dob i antropometrijske parame- jednosti klirensa kreatinina, moguće je
dina statistički se značajno ne razlikuju.
tre prikazana je u Tabeli 8 a u odnosu na objasniti glomerularnom hiperfiltraIsto tako, učestalost patološkog nalaza
trajanje bolesti.
cijom, koja se javlja na početku dijabeovog parametra u ispitanika sa dužim
U odnosu na ispitanike sa trajanjem tesa. Prema istraživanju Mogenesen i
DMT1 manje od 10 sar., (3) i Chiarelli i sar., (22) hiperfiltraUltrazvučni nalaz volumena desnog bubrega u
godina učestalost pa- cija kroz glomerul je odgovorna za naodnosu na trajanje DMT1
tološkog
nalaza volu- stanak nefropatije, dok Lervang i sar.,
Decimalna dob i
<10 godina (n=62)
>10 godina (n=18)
mena
lijevog
bubrega (23) i Dramond i sar., (24) smatraju da
antropometrijski
Nalaz UZ
Nalaz UZ
se statistički značajno mogući mehanizmi odgovorni za uniparametri
Normalan Patološki Normalan Patološki razlikuje u grupi is- štenje bubrežnog tkiva još nisu dovoljno
N; (%)
N; (%)
N; (%)
N; (%)
pitanika sa trajanjem istraženi. Hiperfiltracija glomerula nije
Dob
55 (88.7)
7 (11.3) 15 (83.3) 3 (16.7)A DMT1 dužim od 10 jedina i dovoljna za nastanak nefropaTjelesnu visinu
54 (87)
8 (13) 12 (66.7) 6 (33.3)B godina prema deci- tije, ali udružena sa drugim metaboličTjelesnu masu
56 (90)
6 (10) 12 (66.7) 6 (33.3)C malnoj dobi, tjelesnoj kim i hemodinamičkim poremećajima u
Tjelesnu površinu
53 (85.4)
9 (14.5) 11 (61.2) 7 (38.8)D visini, masi i površini. toku dijabetesa, doprinosi nastanku ove
komplikacije.
Tabela 7. Učestalost normalnog i patološkog nalaza volumena desnog
5.
DISKUSIJA
Veće vrijednosti klirensa kreatinina
bubrega u odnosu na trajanje DMT1 mjerenog ultrazvukom i izračunatog
U t o k u n a š e g ubrzo poslije dijagnostikovanja DMT1 su
u odnosu na decimalnu dob i antropometrijske parametre. AZ = 0.55;
95% CI 0.307572 – 0.784699; P = 0.40, BZ = 0.78; 95% CI 0.523627
istraživanja značajno znak hiperperfuzije i hiperfiltracije glo– 0.935908; P = 0.18, CZ = 1.67; 95% CI 0.409925 – 0.866573; P =
učestalija mikroal- merula bubrega. Duže trajanje navede0.05, DZ = 1.57; 95% CI 0.657879 – 0.986249; P = 0.04 u odnosu na
buminurija bila je u nih poremećaja uz druge hemodinamispitanike sa trajanjem DMT1 manje od 10 godina.
grupi ispitanika kod ske faktore i slabije kontrolisanu bolest
Ultrazvučni nalaz uzdužnog dijametra desnog bubrega
u odnosu na trajanje DMT1
<10 godina (n=62)
>10 godina (n=18)
MED ARH 2009; 63(3) • ORIGINALNI ČLANCI / ORIGINAL PAPERS
135
Mikroalbuminurija i ultrazvučne karakteristike bubrega u djece i adolescenata sa Dijabetes melitusom tip 1
sti istraživanja. U ovoj
fazi su bubrezi uveDecimalna dob i
<10 godina (n=62)
>10 godina (n=18) ćani zbog hiperfiltraantropometrijski
cije, povećanog hidroNalaz UZ
Nalaz UZ
parametri
statskog pritiska u gloNormalan Patološki Normalan Patološki merulima i hipertroN; (%)
N; (%)
N; (%)
N; (%)
fije pojedinih nefrona
Dob
57 (91.9)
5 (8.1) 15 (83.3) 3 (16.7)A (12, 18, 26). Poredeći
Tjelesnu visinu
53 (85.5)
9 (14.5) 13 (72.3) 5 (27.7)B dimenzije desnog i liTjelesnu masu
56 (90)
6 (10) 13 (72.3) 5 (27.7)C jevog bubrega evidenTjelesnu površinu 47 (75.8) 15 (24.2) 11 (61.2) 7 (38.8)D tno je da su procesi u
DMT1 obostrani, diTabela 8. Učestalost normalnog i patološkog nalaza volumena lijevog
fuzni i hronični. U
bubrega u odnosu na trajanje DMT1 mjerenog ultrazvukom i izračunatog
izraženoj bubrežnoj
u odnosu na decimalnu dob i antropometrijske parametre. AZ = 1.67;
95% CI 0.035785 – 0.414178; P = 0.05, BZ = 2.06; 95% CI 0.096949
insuficijenciji i termi– 0.534802; P = 0.02, CZ = 2.31; 95% CI 0.172986 – 0.642549; P =
nalnim stadijumima
0.01, DZ = 2.19; 95% CI 0.133427 – 0.590075; P = 0.03 u odnosu na
drugih parenhimskih
ispitanike sa trajanjem DMT1 manje od 10 godina.
bubrežnih bolesti dimenzije bubrega se
dovest će do mikroalbuminurije i dalje
značajno smanjuju (25, 11). Kod dijabeprogresije nefropatije.
tesne nefropatije veličina bubrega se ne
U grupi naših ispitanika sa trajanjem
smanjuje proporcionalno funkcionalDMT1 manje od 10 godina, uzdužni dinom oštećenju (27, 18, 26). Prije su prijametar i volumen oba bubrega nisu bili
sutni klinički i biohemijski parametri neznačajno promijenjeni u odnosu na korifropatije, nego što se promjena na bubreštene standarde za dob i antropometrijzima ultrazvučno mogu registrovati kod
ske parametre. I drugi autori u sličnim
oboljelih od DMT1 (19, 26).
istraživanjima su imali gotovo istovjetne
Učestalost patološkog nalaza volurezultate (12, 25, 19, 18). Dok u ispitanika
mena desnog bubrega se značajno rakod kojih DMT1 trajao duže od 10 gozlikuje u ispitanika sa trajanjem DMT1
dina, značajno je učestaliji patološki naduže od 10 godina prema tjelesnoj masi
laz uzdužnog dijametra i volumena oba
i tjelesnopj površini. Patološki nalaz vobubrega u odnosu na dob i antropomelumena lijevog bubrega je bio značajno
trijska mjerenja. Nije jasno utvrđena poučestaliji u istoj grupi ispitanika prema
vezanost između dužine trajanja bolesti,
decimalnoj dobi, tjelesnoj visini, tjelekliničkih manifestacija i morfoloških, ulsnoj masi i tjelesnoj površini. Ta razlika
trazvučnih promjena koje se mogu regidesnog i lijevog bubrega, s obzirom na
stravati ultrazvučnim pregledom. Može
obostrani parenhimski proces, ne može
se zaključiti da u ispitanika koji boluju
se pouzdano objasniti (12, 18, 26). Zbog
od DMT1 duže od 10 godina, a pri tome
ograničenja studije ove razlike se javljaju,
su oboljeli u dobi od 2. do 16. godine žiali su nepouzdane i malo vjerovatne.
vota, postoji uvećanje uzdužnog dijaSmatra se da u dijabetesu uvećanje vometra bubrega uočljivo B modom ultralumena bubrega nastaje zbog zadržavazvučnim pregledom.
nja soli i vode, te promjena na krvnim suZapaženo je, da je kod tih ispitanika
dovima (26, 18, 10, 4). Uvećanje dimenučestaliji patološki nalaz uvećanog uzzija i volumena bubrega je jedna od kadužnog dijametra desnog bubrega prema
rakteristika DMT1 u fazi hipertrofijske
tjelesnoj visini i tjelesnoj površini, koji
hiperfiltracije (19).
korelira sa učestalijom mikroalbuminurijom. U istoj grupi ispitanika, sa traja6. ZAKLJUČAK
njem DMT1 duže od 10 godina, znatno
Praćenje mikroalbuminurije i metaje učestaliji patološki nalaz uvećanog uzboličke kontrole bolesti uz ultrazvučni
dužnog dijametra lijevog bubrega u odnalaz bubrega može doprinijeti definisanosu na tjelesnu visinu, tjelesnu masu i
nju optimalnog vremena za screening i
tjelesnu površinu. Zašto je uzdužni dijaprevenciju nefropatije kod djece i adolemetar desnog bubrega promijenjen samo
scenata sa DMT1.
u odnosu prema tjelesnoj masi i tjelesnoj
površini nije jasno. Prema tjelesnoj masi
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Kontakt adresa autora: Mr. dr. sc.
Evlijana Hasanović, Klinika za dječije bolesti,
Univerzitetski klinički centar Tuzla, 75 000 Tuzla,
Bosna i Hercegovina, E mail evlijanah@yahoo.
com telefon 00387 61 887721.
Colposcopic Changes Based on Number of Sexual Partners, Births, and Contraceptives Use
Colposcopic Changes Based on
Number of Sexual Partners, Births,
and Contraceptives Use
Myrvete Paçarada, Shefqet Lulaj, Gyltene Kongjeli, Niltene Kongjeli, Hana Qavdarbasha, Bujar Obërtinca
Gynecology/Obstetrics Clinic, University Clinical Centre of Kosova, Prishtina, Kosovo
Original paper
SUMMARY
Objective: The aim of this study was to determine the role of colposcopy and cytodiagnosis in the early detection of pathological changes in the uterine cervix and the association between the number of birth, sexual
partners and colposcopic changes and cytological atypia. Material and Methods: Colposcopic changes in the
cervix in relationship to number of births, abortions, and number of sexual partners were determined based
on data from examinations performed at the Obstetric-Gynecologic Clinic in Prishtina, Kosovo during 2006 and
2007. The 500 examined patients were categorised in several groups. Results: All study patients underwent colposcopy. Colposcopic atypia was observed in 70 patients (14%), and 77 (15.4%) had other abnormal findings.
The amount of colposcopic atypia increased with an increasing number of sexual partners. In the group with
three or more sexual partners (n = 43) the rate was 62.8%. Infections were also more frequent in this group;
of the 43 patients examined, 51.3% (22 patients) had infections, whereas in the group of 76 patients with only
one sexual partner, 18.3% had infections and only 20.6% used contraceptives. Conclusion: Number of births,
abortions, number of sexual partners, and contraceptive use directly affect colposcopic changes and cytological atypia.
Keywords: colposcopy, endometrial changes. contraceptives
1. Introduction
The uterine cervix is very susceptible to infections and is thus vulnerable to numerous pathological processes
(1,2,3,4,5,6). In addition, injuries to the
cervix incurred while giving birth or injuries incurred during an abortion or the
course of other gynecologic or obstetric procedures often result in disorder
of the cervix’s functional and anatomic
structure (7).
In women, cervical cancer is a major
cause of death from malignant diseases
(1). Three different groups of factors that
increase the risk for this disease have
been described (8): (1) infection with human papilloma virus (HPV) and the duration of viral infection; (2) conditions
such as multiparity and poor nutrition
that compromise the immune system;
and (3) lifestyle factors such as smoking,
contraceptive use, and number of sexual
partners, as well as the age at menarche.
The link between cervical cancer
and human papilloma virus (HPV) infection is well established (4). HPV infections are more frequent in more sexually active females, and the virus is
found in more that 90% of intraepithelial lesions detected in younger women
(5). Although, the majority of the infections pass after several months or years,
a small percentage of the virally infected
cells slowly undergo malignant transfor-
mation (9, 10), with invasive disease affecting mostly older women. The role of
immunodeficiency virus (HIV) in the
pathogenesis of cervical cancer is not
clear yet, although it a has been shown
that HPV is more frequently present in
HIV-seropositive patients than in those
who are HIV-seronegative (11).
Cervical cancer can be detected and
characterised with respect to the involved area, degree of differentiation,
and atypia in the vagina by examination with a special binocular magnifier, the colposcope. The main function
of colposcopy is the early diagnosis of
pre-cancerous cells in the cervix. In the
majority of patients, it enables the early
detection of cancer and thus allows the
use of more conservative treatment (including electrocautery, diathermy, cautery, cryotherapy, and laser) of atypical
changes, thereby avoiding more aggressive conisation and gynecologic surgery.
The early detection of cytological
changes is further enhanced by the combined use of the cytological Papanicolau
technique and colposcopy. Cytological
analysis detects endocervical changes,
which are not seen with colposcopy.
Together, these methods result in the
early and certain detection of carcinoma
of the cervix in over 85% of patients.
Moreover, with the advent of organised
screening programs, cancer of the cer-
vix has become relatively rare in young
women (<25 years of age). Instead, cervical cancer mainly affects older women,
especially those who have not benefited
from screening (2). Despite the advent
of these non-invasive methods for early
detection of malignant diseases of the
cervix, in Kosovo, early detection is relatively rare because of unfavourable socio-economic conditions.
The aim of this research study is to
obtain more accurate data on the effect
of different factors in the pathology of
the cervix, more specifically the role of
abortions, number of births, and number of sexual partners.
2. Patients and Methods
To study the relationship between
colspocopic changes in the uterine cervix and number of births, abortions, and
sexual partners, data from examinations
performed at the Obstetric-Gynecologic
Clinic in Prishtina, Kosovo during 2006
and 2007 were analysed.
Vaginal smears were taken for cytological analysis, after which colposcopy was performed using a ZeissOberkochen colposcope, with a 20×
magnification. Extended colposcopic examination consisted of swabbing the vagina and cervix with 3% acetic acid and
using these samples for the Schiller test
with iodine. Tissue from abnormal areas was biopsied and submitted for histopathological testing.
The 500 patients in the study were
classified in groups based on the numbers of births, abortions, and sexual
partners. Group 1 comprised patients
who had not given birth or had abortions; group 2, patients who had not
given birth but possibly had a spontaneous or induced abortion; group 3, patients had given birth once and possibly a spontaneous or induced abortion;
group 4, patients had given birth twice
and possibly a spontaneous or induced
abortion; and group 5, patients had given
birth three or more times.
Our research did not include pregnant women or women who had undergone any procedures involving the cervix
(conisation, thermocoagulation, polypectomy, or plastic surgery of the cervix).
3. Results
All women who participated in the
study underwent a colposcopy examination (Table 1). Atypical colposcopic
changes were detected in 70 women
MED ARH 2009; 63(3) • ORIGINALNI ČLANCI / ORIGINAL PAPERS
137
Table 1. Atypical and abonormal colposcopic findings according to patient group
Colposcopic Changes Based on Number of Sexual Partners, Births, and Contraceptives Use
Atypical and
abnormal
Table 1. Atypical and abonormal colposcopic findings according to colposcopic
patient group
findings
Atypical and
abnormal
colposcopic
findings
Atypical
Group
Changes
Atypical Transformation Zone
White epithelium
Base of leucoplaky
Mosaic
Leucoplakia
Atypical Vascularization
Suspicion of malignancy
Total number of changes
Inflammatory changes
True erosion
Condyloma accuminata
Papilloma
Polyps
Total number of changes
1
0
0
0
0
0
0
2
0
1
0
3
-
2
3
0
2
0
0
4
16
0
1
1
18
3
9
Group
Total
number of such changes was higher in
Changes
1 2 3 4 5 N
women having
Atypical Transformation
Zone intercourse
0 3 once
9 a7 week
23 42
Total
White epithelium
- - more
than in those who reported
freBase of leucoplaky
- quent intercourse, and0 for0 colpitis,
lac-Mosaic
2 3 13 18
N Leucoplakia
%
erations, and atypical colposcopic
0 2 5 3 find18 28
42 Atypical
8.4 Vascularization
0 0 significant.
3 4 23 30
ings, the differences were
of malignancy
0 0 0 1 1
- Suspicion
However,
there may be 00other
factors that
number of changes
4 13 10 43 70
- Total
explain
these
changes,
as
women
Inflammatory
changes
2
16
11 11 who
20 60
18 3.6
True erosion
0 0 0 as
1 well
5 6
did
not
have
sexual
intercourse
28 5.6
Condyloma accuminata
1 1 1 2 0 5
as
widowed,
divorced,
and
older
women
30
6
Papilloma
- 1 Polyps
0.2
were included in the group
0 1of women
2 0 en3 6
70 Total
14 number
of changes
3 18 a 14
14 28 77
gaging
in intercourse once
week.
4 5
7 23
Atypical
2 3 13
5 3 18
3 4 23
0 0 1
13 10 43
Abnormal
11 11 20 60
12
0 1 5 6 1.2
1 2 0 5
1
0
2 0 3 6 1.2
14 14 28 77 15.4
4. Discussion
The main causes of malignant processes in the cervix are now known.
Abnormal
Among these, experimental and epidemiologic research has found that the on(14.0%), and other findings were noted ceptive use, the frequency of all other
set of carcinoma of the cervix is directly
in 77 (15.4%). Based on the group clas- changes was significant in women who
sifications, the frequency of changes in- used contracreased from the first group, in which ceptives com- Table 2. Patients based on residence and age at first sexual activity
only three patients had other findings pared to those
Age at first
Village residents
City residents
Total
and none had atypical changes, to the who did not.
sexual
%
Number
%
Number
%
fifth group, in which 43 patients had L ac e r at i o n s activity, years Number
atypical changes and 28 had other find- were detected
≤19
58
40.56
145
40.62
203
40.60
ings (Table 1).
in 35 (34.0%)
Table
2. Patients
based onofresidence
and ageofatthe
first103
sexual
Nearly
half (46.8%)
the women
pa- activity20-24
63
44.06
171
47.9
234
46.80
inAge
the at
study
became
sexually
active
bet
i
e
n
t
s
w
h
o
first
Village residents
City residents
Total25+
22
15.38
41
11.48
63
12.60
tween
the ages of 20 and 24 years, and used contrasexual
40.6% reported
sexual activity
at
age ceptives
and
Total % 143
100.00 357
100.00 500
100.00
%
Number
%
Number
activity, years Number
19 (Table 2). No major differences were in 66 (16.6%)
3. Marital status of the study participants
noted≤19
between58women who
in vil- of40.62
the 397 203
who Table40.60
40.56lived145
Table 3. Marital status of the study participants
lages and those who lived in cities, except did not.
Marital status
Total
63
44.06
171
47.9
234i46.80
Marital status
Total
that a20-24
larger proportion
of
village women
A pprox
Number of
Not
Married Divorced Widowed Number
%
became sexually active at an older age mately 44% of Number
marriages
of married
Not
Married Divorced Widowed Number
%
25+
22
15.38
41
11.48
63
12.60
(>25 years) compared with city women the women in
marriages
married
0
62
62
12.4
(15.8%
the
study500
reTotal vs. 11.48%,
143 respectively).
100.00 357
100.00
100.00
0
62
62
12.4
1
387
31
5
423
84.6
The majority of the women in the p or t e d t h at
387
5
study were married (80%); 6.6%, di- they engaged
21
-10
131
11423
2.284.6
vorced; 1.0%, widowed; and 12.4%, not in sexual inter2
3+
-310
11
4 11
0.82.2
married (Table 3).
course three
3
1
n (%) 62 (12.4)
400 (80)
33 (6.6)
5 (1)
5004
1000.8
The study participants were as- or more times Total,3+
signed to one of the five groups de- p e r w e e k ; Total, n (%) 62 (12.4) 400 (80) 33 (6.6)
5 (1)
500
100
scribed above. Groups 1–5 consisted of 30.4%, twice
100 women each. Of the 100 women in per week; and
Table 4. Number of births and abortions
group 5, 60 had 3-4 births, and 12 had 25.5%, once a
and abortions
of abortions
Total
7 or more births. Regarding spontane- week (Table Table 4. Number of birthsNumber
ous and induced abortions, nearly half 6). No conof abortions
Total%
Number
0
1–2Number3–4
5–6
7+
N
of the women (235, 47.0%) reported no clusions could of births
Number
0
1–2
3–4
5–6
7+
N
%
abortions; 42.2% (211), 1 or 2 abortions; be reached re0
100
91
9
200
40.0
of births
8.2%, 3-4 abortions; and 1.6%, 5-6 abor- ga rd i ng t he
10
57
38
59
-- 100
20.0
100
91
200
40.0
tions. Five patients had undergone 7 or r o l e o f t h e
more abortions (Table 4).
frequency
21
45
41
135
1100
20.00
57
38
100
20.0
The number of women who used con- of sexual in3-4
20
21
1113
51
3
60100
12.00
2
45
41
20.00
traceptives as a means of family plan- tercourse in
5-6
820
15
211
15
23
2860
5.60
3-4
21
12.00
ning was relatively low (103, 20.6%), but p a t h o l o g i pathological changes were observed sig- c a l ch a nge s
7+
58
515
12
11
- 2
1228
2.40
5-6
5.60
nificantly more often in this group of pa- in the cervix.
Total
235
211
411
81
550012
100.00
7+ N
5
5
2.40
tients (Table 5). Although the number of Perhaps sur42.20
8.20
1.60
1.00
100.00
infections did not correlate with contra- prisingly, the Total %N 47.00
235
211
41
8
5
500
100.00
%
138
MED ARH 2009; 63(3) • ORIGINALNI ČLANCI / ORIGINAL PAPERS
47.00
42.20
8.20
1.60
1.00
100.00
-
%
8.4
3.6
5.6
6
0.2
14
12
1.2
1
0
1.2
15.4
Colposcopic Changes Based on Number of Sexual Partners, Births, and Contraceptives Use
risk factors for questionnaire answered by the patients,
the onset of the study population ranged in age from
χ test
Use of contraceptives
pre-malignant 17 to 55 years, with nearly the majority
Diagnosis
(P value)
Yes
No
Total
and malignant between 20 and 29 years (233 women,
(n = 103) (n = 397) (n = 500)
cervical dis- 46.6%). Among the women in the age
Colpitis, n (%)
30 (29.1)
85 (1.4)
115 (23.00)
>0.01
eases: parity groups 19 years and younger and over
and promiscu- 50, pathological findings were identiity (16). While fied in 13 (2.6%).
Lacerations, n (%)
35 (34.0)
66 (16.6) 101 (20.20)
<0.01
The cervical epithelium is very sensiincreasing
parity as a risk tive and vulnerable during adolescence,
Erythoplakia, n (%)
20 (19.4)
41 (10.3) 61 (12.20)
<0.01
factor for cer- especially in those under the age of 19,
v ica l cancer which may in part explain the associais supported tion between age at first sexual activOther atypical cervical findings, n (%) 5 (4.9)
16 (4.0)
21 (4.20)
<0.01
by abundant ity and cervical cancer. Accordingly, we
data and has paid special attention to this age group,
long been rec- even though for many women sexual life
Total, n
90
208
298
<0.01
ognized, pro- begins with marriage (16). This is parAdditional examinations of atypia
miscuity is a ticularly true for women over the age of
Atypical colposcopy, n (%)
39 (37.9)
73 (18.4) 112 (22.40)
<0.01
relatively re- 50. However, we found that 40.6% of the
cent issue, and women began an active sexual life before
Papanicolau (groups III-IV), n (%)
18 (17.5)
24 (6.0)
42 (8.40)
<0.01
there are sig- the age of 19, with no significant differSchiller test (positive), n (%)
30 (29.1)
61 (15.4) 91 (18.20)
<0.01
nificant prob- ence between women from urban and
lem s i n ob - rural areas. Atypical colposcopic findrelated to age at first sexual activity (12).
taining accu- ings were detected in 12% of women who
The number of atypical colposcopic rate data on the number of sexual part- became sexually active at an age younger
findings increases with increasing age. ners.
than 25 compared with 1.20% among
Cytological changes of types III, IIIa,
As determined from the results of a women who became sexually active afIIIb, IV, and V, based on the classifiTable 6. Atypical changes in the cervix as a function of the frequency of sexual
cation system of Papanicolau, also inintercourse
crease with age. In our study, there were
Group 1
Group 2
Group 3
Group 4
Group 5
Total
Frequency (n = 100) (n = 100) (n = 100)
(n = 100) (n = 100) (n = 500)
Diagnosis
two cases (0.40%) of cytological changes
of sexual Births, 0; Births, 0; Births, 1;
Births, 2; Births, 3;
N (%)
in women 20–29 years of age, but there
intercourse
Ab, 0
Ab, +
Ab, +/Ab, +/Ab,+/were 34 cases (6.80%) among women Colpitis
1
9
13
5
5
12
44 (8.80)
2
2
6
4
8
6
26 (5.20)
>40 years old. These statistics are par3+
7
14
9
10
5
45 (9.00)
ticularly important because malignant
Total
18
33
18
23
23
115 (23.0)
processes in the cervix are preceded by Lacerations
1
0
0
4
10
21
35 (7.00)
a prolonged period of cytological atypia,
2
0
0
3
11
22
36 (7.20)
3+
0
0
5
9
16
30 (6.00)
and the highest frequency of cervical
Total
0
0
12
30
59
101 (20.20)
neoplasia involves women 45–55 years
Erythroplakia
1
0
1
4
4
4
13 (2.60)
of age (13).
2
0
0
3
11
13
27 (5.40)
In our study, the number of patients
3+
2
5
2
5
7
21 (4.20)
Total
2
6
9
20
24
61 (12.20)
who used contraceptives was relatively
1
1
1
2
2
5
11 (2.20)
small (103 women, 20.6%). The preferred Cervical atypia
2
0
1
1
0
4
6 (1.20)
contraceptive methods were intrauterine
3+
0
0
0
0
4
4 (0.80)
devices and birth control pills. AtypiTotal
1
2
3
2
13
21 (4.20)
1
10
15
15
21
42
103 (20.60)
cal colposcopic and cytological find- Total
2
2
7
11
30
45
95 (19.00)
ings were significantly more apparent
3+
9
19
16
24
32
100 (20.00)
in women using contraceptives: for the
N
21
41
42
75
119
298 (59.60)
former, 37.9% compared with 18.4% for
%
4.20
8.20
8.40
15.00
23.80
59.60 (-)
non-users, and for the latter, 17.5% com- Additional
pared with 6.0% for non-users. Similar diagnostic
examinations
results have been reported by other au- Atypical
1
1
6
8
11
17
43 (8.60)
2
1
3
6
4
16
30 (6.00)
thors (14). Other atypical processes show
3+
1
10
9
5
14
39 (7.80)
a relatively similar tendency.
Total
3
19
23
20
47
112 (22.40)
We also determined that atypical Papanicolau
1
0
1
2
5
10
18 (3.60)
colposcopic findings positively corre- (groups III-IV)
2
0
0
1
1
11
13 (2.60)
3+
0
0
3
3
7
13 (2.60)
lated with the number of births, increasTotal
0
1
6
9
28
44 (8.80)
ing from three cases in the group with
Schiller
1
0
5
5
7
16
33 (6.60)
no births to 47 cases in the group with (positive)
2
0
2
4
2
16
24 (4.80)
three or more births (15).
3+
0
4
10
7
13
34 (6.80)
Total
0
11
19
16
45
91 (18.20)
Other authors have identified two
Table 5. Use of contraceptives and changes in the cervix
2
MED ARH 2009; 63(3) • ORIGINALNI ČLANCI / ORIGINAL PAPERS
139
Colposcopic Changes Based on Number of Sexual Partners, Births, and Contraceptives Use
ter the age of 25. Erythoplakia was more
frequent in the former group, which had
31 cases (6.20%) versus five cases (1%) in
the latter group.
Due to the link between promiscuity
and cervical cancer, we questioned the
women regarding frequency of sexual activity. Slightly less than half the women
(222, 44.4%) reported engaging in sexual intercourse more than three times
per week, but we did not obtain data as
to whether intercourse was always with
the same partner. There were no significant differences between this group and
the group that engaged in sexual activity once per week. However, colpitis was
more frequent in the group with three
or more sexual partners (51.2%) than
in the group of women with one partner (18.3%). Both HPV and Chlamydia
trachomatis have been linked to cervical changes, but their effects on the cervix are independent of each other (17).
Atypical colposcopic findings tended
to increase with an increasing number of partners: 17.8% in the group with
one partner but 62.8% in the group with
three or more partners.
The association between the number
of births and abortions and pre-cancerous and cancerous processes in the cervix uteri has been addressed by many authors but without a consensus (10). Erythoplakia increases with an increasing
number of births. Nine cases were detected in the group of women with one
birth; 20 cases, in the group with two
births; and 24 cases, in the group with
three births. These increases were highly
statistically significant.
Cervical lacerations during the birth
process, particularly in women who carried past term, are related to pathological
changes in the cervix and were detected
in 101 of the 500 women (20.20%) who
participated in the study, and in 33.67%
of the women who had given birth. These
figures are higher than the 11.5/36.67%
reported in a previous study (2).
In atypical colposcopic findings,
there is a dominant atypical zone of
transformation. This was not seen in
the group with no births, whereas there
140
Women’s colposcopy experience and preferences: a mixed methods study. 14 January 2008.
8. Terzic B. Uloga kolposkopije u otkrivanju
HPV na donjem genitalnom traktu zene.
Jugoslovenska skola za patologiju cerviksa, vagine vulve i kolposkopiju, Beograd 1996:16-8.
9. Cullhed S. Carcinoma cervicis uteri stages
I and IIa. Treatment–histopathologyprognosis.Acta Obstet Gynecol Scand
Suppl. 1978;75:1-149.
10. Stanimirovic B. Infekcija cerviksa humanism papilloma virusima i njena uloga u
onkogenezi.Patologia cerviksa. Beograd,
1996;27-9.
11. Divisions of HIV/AIDS Prevention. HIV
and Its Transmission. Centers for Disease
Control & Prevention. Retrieved on, 200605-23
12. Marrazzo JM, Martin DH. Management of
5. Conclusion
Women With Cervicitis. Clin Infect Dis,
The number of births, abortions, and
2007; (S3): S102. doi:10.1086/511423.
sexual partners as well as contraceptive 13. Popovic D. Razvoj kolposkopije I njeno
use directly influenced the frequency
mesto u detekciji prekancerozivnih promena i ranih stadijuma carcinoma donjeg
of atypical colposcopic and cytological
dela genitalnog trakta zene.Jugoslovenska
findings. Our results show that the numskola za patologiju cerviksa, vagine, vulve
ber of births and the number of sexual
i kolposkopiju.Beograd, 1996.
partners are directly related to patholog- 14. Stranimirovica B. Faktori rizika u nasical changes in the cervix. Both colpostanku maligne bolesti grlica materice,
copy and cytology demonstrated an inznacaj njihovog ranog otkrivanja, za profilaksu, terapiju i prognozu bolesti. Dokcrease in pathological findings with intorska disertacija, Beograd, 1988.
creasing patient age.
15. Berisavac M. Nova nomlenklatura u kolposkopiji: Znacaj jedinstvenih kriterijuma
REFERENCES
u kolposkopskoj diagnostici. Jugoslovenska
1. Cunningham G, Leveno K, Bloom LS,
skola za patologiju cerviksa, vagine, vulve
Hauth CJ, Gilstrap L., Wenstrom K, Wili kolposkopiju.Beograd, 1996.
liams Obstetrics, 22nd edition, 2005; 16. WorkoWski K, Berman S. Sexually trans1303-8.
mitted diseases treatment guidelines,
2. Elsebeth Lynge Danish Cancer Registry,
2006. MMWR Recomm Rep, 2006;55 (RRInstitute of Cancer Epidemiology, Dan11):1–94.
ish Cancer Society, Landskronagade 66, 17. Claas ECJ, Melchers WJG, Niesters HM,
DK-2100 Copenhagen, Denmark. ScreenRuud van Muyden, Stolz E, Quint WGV.
ing for cancer of the cervix uteri. May 16,
Infections of the cervix uteri With hu2005
man papillomavirus and Chlamydia tra3. American Cancer Society. What Are the
chomatis Journal of Medical Virology,
Risk Factors for Cervical Cancer?. Re2005;37(1):54-7.
trieved on 2008-02-21.
18. Kesic V. Normalni i patoloski kolposkop4. G r g u r e v i q M , P a v l i c Z , G r i z e l j ,
siki nalazi. Jugoslovenska skola za patologV; [Gynecology, 3rd ed., Croatioan].
iju Cerviksa, vagine, vulve i kolposkopiju.
Zagreb:Jugoslovenska Medicinska Nak1996;107-9.
lada 1987; 110-15.
19. Eckerert et al. Inflammation on Papanico5. Poevonen J, Teisal K, Heinonen P K et al.
laou. Obstet Gynecol, 1995;86:360-6.
Endometrititis and acute salpingitis associated with Chlamydia trachomatis and
herpes simplex virus type. Wo. Am J ObCorresponding author: Myrvete Paçarada,
stet Gynecol, 1985; 65:288-91.
MD, PhD. Gynecology/Obstetrics Clinic;
6. Bukovi D. et al. Sexual Life after Cervical
University Clinical Centre of Kosova, Rrethi i
Carcinoma, Coll. Antropol. 2003;1: 173–
Spitalit pn. 10 000 Prishtina Phone: +377 44
80.
111089, e-mail: myrvetepaqarada@hotmail.com
7. Wancutt DRS, Greenfield SM, Wilson S.
were 23 cases in the group with three or
more births.
Poor economic conditions negatively
impact health, including a general weakening of the immune system (20). Furthermore, the frequency of gynecologic
examinations is an important factor in
the early detection of atypical findings
in the cervix.
Contraceptive use may also play
a role in the prevalence of pathological changes in the cervix, as seen in
five women in the present study. Interestingly, this effect was also evident in
women who used mechanical contraceptive devices.
MED ARH 2009; 63(3) • ORIGINALNI ČLANCI / ORIGINAL PAPERS
Diagnostic Value of CEA in Pleural Fluid for Differential Diagnosis of Benign and Malign Pleural Effusion
Diagnostic Value of CEA in Pleural
Fluid for Differential Diagnosis of
Benign and Malign Pleural Effusion
Tatjana Radjenovic-Petkovic1, Tatjana Pejcic1, Desa Nastasijević-Borovac1, Milan Rancic1, Danijela
Radojkovic2, Milan Radojkovic3, Ivanka Djordjevic1
Clinic for Lung Disease, Clinical Center Nis, Serbia1
Clinic for Endocrinology and Toxicology, Clinical Center Nis, Serbia2
Clinic for Surgery, Clinical Center, Nis, Serbia3
Original paper
Summary
The diagnostic value of tumor markers in pleural fluid is still the subject of debate. The aim of this work was to
evaluate diagnostic value of carcinoembryonic antigen (CEA) in pleural fluid for differentiating malignant from
non malign pleural effusion, and their additive value to cytological examination. Design: Prospective, case control study. Setting: Tertiary University hospital, Clinic for Lung Disease, Knez Selo. Patients: Eighty two patients
with pleural effusion, forty one with malignant, and forty one with non malignant pleural effusion. Measurements and results: Levels of CEA in pleural fluid was measured by IRMA CEA methods, INEP Belgrade. Patients
with lung cancer were found to have significantly higher CEA levels than patients with non malign pleural effusion. Using cut off values of 2.4 ng/ml, the sensitivity of marker was 78%, and specificity 95.1 % (CI 95%). The
addition of CEA to cytology increase diagnostic rate from 68 to 85.3%. Conclusion: CEA may represent a helpful
adjunct to cytology in order to include malignancy as probable diagnosis, thus guiding the selection of patients
for more invasive procedures.
Keywords: pleural effusion, CEA, cytology
2.3. Statistical analysis
Non parametric analysis wes used
to make group comparation. Differences between two independent groups
were determinated by means of the Man
Whitney U test. In an attemp to establish a sensitivity-specifity relationship,
reciever-operating characteristic (ROC)
curves was constructed, using values
levels of CEA in patients with malignant pleural effusion, and patients with
benign pleural effusion as controls. Valus of p less than 0,05 were considered
as significant.
3. Results
Of 82 subjects, 41 (group I) had a malignant, and 41 (group II) had non malign pleural effusion. A detailed account
of the etiology is presented in table 1.Of
41 patients with malignant pleural effusion, 21 subjects (51,2%) were male, and
20 (48,8%) were female. The mean age in
this group were 62,8 years (range 48-80
years). Of 41 benign cases, 29 subjects
(70,8%) were male, and 12 (29%) were
Effusion were conNeoplastic
Non neoplastic
sidered as maligetiology
number
%
etiology
number
%
nant if one of the
28 68,29 parapneumonic
13 31,70
following critheria Lung
mesothelioma
2
4,87
empyema
8 21,95
was met: 1. DemonBreast
4
9,76
tuberculosis
9 21,95
stration of maligCongestive
nant cells at cyth- Ovary
2
4,87
7 17,07
heart failure
ological examina1
2,44 Liver cirhosis
2
4,88
tion 2. Demonstra- kidney
Dressler
tion of malignancy uterus
1
2,44
1
2,44
syndrome
on pleural biopsy
Connective
speciement. The prostate
1
2,44
1
2,44
tissue disease
critheria for non
1
2,44 Traumatic
1
2,44
malignant effusion leukemia
liver
1
2,44
have been refered
total
41 total:
41
elswere (5).
Table 1. Ethiology of the effusions
2.2. CEA
measurment
Pleural fluid for
female, mean age 63,1 years (range 25CEA mesurment were colected and
85 years). The histological tipes of neofrosen to -70oC. The levels of CEA were
plasm are shown in table 2.
measured using immunoradiometric assay, IRMA CEA (INEP, Belgarde, Serbia).
n=41
%
The assays is based on two monoclonal Hystological types
antibodies specific for CEA, not cross re- adenocarcinoma
22
53,66
active with other CEA related moleculs, Small cell carcinoma
4
9,76
suited for use in solid phase assays. The Squamous cell carcinoma
4
9,76
assays is standardised against 1st Inter- mesothelioma
2
4,87
national Reference Preparation of CEA, lymphoproliferative
1
2,44
2. Materials and methods
73-601 (NIBC, WHO). Detection lim- others*
8
19,51
2.1. Patients
its of the assays is 0,5 –l mg. Inter and
We collected pleural fluid from 82 intraassay variations are less than 10%. Table 2. Malignant effusion: histological types,
patients who were admited to the Clinic The bound radioactivity was measured *undifferentied n=6, hepatocarcinoma n=1, rénal
carcinome n=1
for lung disease due to pleural effusion. using g-counter.
1. Introduction
Pleural effusion is common problem in clinical practice. The differential
diagnose is diverse, but most common
cases include malignancy, congestive
hurt failure, tuberculous and pneumonia related effusion (1). Malignant pleural effusion can be initial presentation
of the disease in 10-50% of patients (2).
Cytology is standard method for the diagnosis of malignant effusion, but sensitivity of cithology is 40-80%, depending of tumor tipes (3). Altrough thoracoscopy can establish the diagnosis in
aproximately 90% of patients with malignancy (4), this procedure may not be
available at all facillites, or may be to
invasive for patients with poor performance. Several tumor markers in pleural
fluid have been evaluated to distinguih
benign from malignant pleural effusion,
but carcinoembrionic antigen has been
studied the mostResults in literature are
still contraversal. The aim of this study
were to investigate role of CEA in distinguishing malignant and non malign
pleural effusion, and their aditive value
to cytological examination.
MED ARH 2009; 63(3) • ORIGINALNI ČLANCI / ORIGINAL PAPERS
141
Diagnostic Value of CEA in Pleural Fluid for Differential Diagnosis of Benign and Malign Pleural Effusion
CEA (ng-ml)
malignant
benign
n
41
41
Mediana
44,50
1.200
mean±SD
55,76± 57,25
1,23±0,55
SE
Max
9,05
0.113
164,00
2.400
Table 3. Pleural fluid level of CEA
Sensitivity
of citology
0,38
is 20-80%,
0.890
depending of tumor tipes
Min
adenocarcinoma (light). Therefore, value
of pleural fluid CEA would be limited in
the PE other than adenocarcinoma. The
adition of CEA to citology increase diagnostic rate from 68 to 85,3%. We shown
that CEA can imrove citology sensitiv-
The median, mean and standard de(2) In aproxiviation levels for the CEA in group I
sensitivity
Specifity
PPV
NPV
mately 40% of
%
%
%
%
and group II are shown in table 3. The
cases, citology
ROC curve with cut off value, specifity
28/41 (68,2)
41/41 (100)
28/28 (100) 41/54 (75,92)
does not pro- citology
CEA
32/41
(78,05)
40/41
(97,56)
32/33
(96,97) 40/49 (81,63)
v ide a de c iCEA+
citology
35/41
(85,36)
40/41
(97,56)
35/36
(97,22) 41/46 (89,13)
sive answer to
wheather pleu- Table 5. Operating caracteristics of CEA and citology in pleural fluid
ral effusion is
malignant or
ity, but it depends from histological tipe
not (7). In that cases, many autors sugof tumor.
gest the evaluation of different tumor
In the cases of suspicion malignant
markers in pleural fluid . Therefore, we
pleural effusion with negative citological
evaluated the diagnostics utility of CEA
the determination of CEA may be helpto differentiate malignant from benign
ful as a complementary tool for the difpleural effusion. CEA is mostly used tuferential diagnosis of pleural effusion.
mor marker, since its not tumor specific.
Results of his usefull is contraversal. It
REFERENCES
is difficult to drow comparation amnog 1. Light RW. Tumor Markers in Undiagnosed Pleural
Figure 1. Receiver operating curves for CEA levels
such studies, since there are differences
Effusions. Chest 2004, 126; 1721-22.
in pleural fluid
in numberof patients and etiology of ef- 2. Hwa Lee J, Chang JH. Diagnostic utility of serum
and pleural fluid carcinoembryonic antigen, neufusion , as well as lack of uniformity in
ron-specific enolase, and cytokeratin 19 fragments
and sensititivity are shown in graf. 1.
the laborathory metodology, and the
in patients with effusions from primary lung canThe number of positive CEA among pacer. Chest, 2005;128:2298–303.
parametar established as cutt off pointes
tients with malignant pleural effusion
3. Sallach SM, Sallach JA, Vasquez E, Schultz L, Kvale
to determinate specifity-sensitivity, toP. Volume of pleural fluid required for diagnosis of
who have negative cithology findings is
gether with the tumor tipe in in the
pleural malignancy. Chest, 2002;122: 1913-17.
reported in table 4.
groups studied. CEA was found to be 4. Light RW. Pleural effusions related to metastatic
malignancies. In: Light RW, ed. Pleural diseases.
tip tumora
CEA>2,4 ng/ml best single marker in pleural fluid in ac4th ed. Philadelphia, PA: Lippincott, Williams &
cordance to previous reports (2).
Wilkins, 2001:108-34.
Lung adenocarcinoma
3/3
Altroug usually evaluated in terms of 5. Porcel JM, Vives M. Differentiating tuberculous
Squamous cell carcinoma
2/3
from malignant pleural effusions: a scoring model.
sensitivity, specifity and accurency, a vaMed Sci Monit, 2003;9:175–180.
Small cell carcinoma
0/3
riety of criteria have been used to asses 6. Romero S, Fernández C, Arriero JM, Espasa A,
hepatocarcinoma
1/1
Candela A, Martín C,. Sánchez-Payá J. CEA, CA
diagnostic value of CEA in pleural fluid.
15-3 and CYFRA 21-1 in serum and pleural fluid
Adenocarcinoma uteri
1/1
Some autors used a specifity of 100% (8),
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Mesotelioma
0/1 but with poor sensitivity. Because of that,
1996;9:17–23.
7.
Porcel JM, Vives M, Esquerda A, Salud A, Pérez
Table 4. CEA values higher than cut off threshold some groups agee to use specifity of 95%
B, Rodríguez-Panadero F. Use of a panel of tumor
markers (carcinoembryonic antigen, cancer antiamong malignant effusion with negative citology
as the cut off pintes (9). The use of ROC
gen 125, carbohydrate antigen 15-3, and cytokerresults
curve helps to preserve i higher sensitivatin 19 fragments) in pleural fluid for the differential diagnosis of benign and malignant effusions.
ity than when using 100% specifity as a
Specifity, sensitivity, PPV and NPV
2004;126(6):1757-63.
points reference, and avoides the burden 8. Chest,
Villena V, Lopez-Encuentra A, Echave-Sustaeta
of CEA and citology are shown in taof 5% false positive cases. Using ROC
J, Martın-Escribano S, Ortuno-de-Solo J, Esteble 5. Diagnostic yield of citology was
noz-Alfaro J. Diagnostic value of CA 549 in pleucurve, we found that pleural fluid CEA
ral fluid. Comparison with CEA, CA 15.3 and CA
68,2%. The combination use of citology
have high diagnostic accurancy. Our re72.4. Lung Cancer, 2003;9:289-94.
and CEA increased the detection rate
sults are similar with Hwa Lee (2) study 9. Salama G, Miedouge M, Rouzaud P, Mauduyt MA,
of malignant pleural effusion to 85,36%.
Pujazon MC, Vincent C, Carles P, Serre G. Evalu(cut off 5 ng-ml, sensitivity of 82,4%).
ation of pleural CYFRA 21–1 and carcinoembryonic antigen in the diagnosis of malignant pleural
Sensitivity in our study was beeter than
4. Discussion
Br J Cancer, 1998;77:472-76.
in Alatas et all (10) study. Better sensi- 10. effusions.
Alataş F, Alataş O, Metintaş M, Colak O, Harmanci
Pleural effusion is often a clinical
tivity of CEA in our study may be conE, Demir S. Diagnostic value of CEA, CA 15-3, CA
problem in medical practice, as differ19-9, CYFRA 21-1, NSE and TSA assay in pleural
sequence of adenocarcinoma dominaeffusions. Lung Cancer, 2000;31(1): 9-16.
ential diagnosis includes awide wariety
tion, and small group of small cell carof local or sistemic diseases. Any carcinoma and mesothelioma. Measurcinoma can metastase to pleura, but
Corresponding author: prof Tatjana
ment of CEA in pleural fluid improved
the most common primary sites are the
the sensitivity of citology. This fact has Radjenovic-Petkovic, MD, PhD. Clinic for lung
lung, brests, and ovary (6). Histological
disease, Clinical Center Nis, Serbia.
been found in other studies (7,8). Pleuconfirmance of malignancy is still the
ral effusion occurs with all tumor tipes,
only definitive diagnosis of malignancy.
but appert to be the most frequent with
142
MED ARH 2009; 63(3) • ORIGINALNI ČLANCI / ORIGINAL PAPERS
Effects of Extracorporeal Shockwave Lithotripsy on Renal Vasculature and Renal Resistive Index (RI)
Effects of Extracorporeal Shockwave
Lithotripsy on Renal Vasculature and
Renal Resistive Index (RI)
Mustafa Hiros, Mirsad Selimovic, Hajrudin Spahovic, Sabina Sadovic
Urology Clinic, Clinical Center University Sarajevo, Bosnia and Herzegovina
Original paper
SUMMARY
Objective: It is known that ESWL can promote acute renal injuries and long–term complications of renal vasculature. Effects on renal vasculature can be evaluated by color Doppler ultrasonography measuring renal resistive index (RI). This prospective study aimed to determine the influence of number of delivered SW-s, used kV
and changes in renal resistive index. Patients and Methods: Total of 60 normotensive patients, 38 males (63%)
and 22 females (37%), with renal stones 6-18 mm in size were included in this study. Median age was 42.3
years (range 22-55). RI was measured at interlobar artery before, 1, 3, 5 and 30 days after treatment on treated
and contra lateral non-treated kidney. Patients were divided in two groups: Group I (N=25) received 2000SWs;
0-2 units; (0,5 unit each 500SWs) Group II (N=35) received 4000SWs, 0-4 units; (0,5 unit each 500SWs). Results:
In treated kidneys RI significantly increased first and second day after treatment from 0,62±0,05 at baseline
to 0,67±0,05, p<0,001 at first and 0,66±0,05, p<0,007 on the second day after treatment. Increase of RI seven
days after treatment is not significant (0,62±0,05). The contra lateral, non-treated kidney showed significant
changes in RI only first day after treatment (0,64±0,05), p<0,01. One month after the treatment RI is on normal
values in both kidneys. Conclusions: Resistive index -RI is important parameter in evaluation of renal vasculature. Patients treated by ESWL showed a temporary increase in RI two days after the treatment and only
first day in contra lateral non-treated kidney - probably caused by release of substance with vasoconstriction
properties (need further investigations).
Keywords: extracorporeal shock-wave lithotripsy, renal stones, color Doppler ultrasonography,
renal resistive index
tient was 2000 to 4000 SW-s. The mean
maximum 0 to 4 units (energy steps
loaded in kV, voltage was 21.6 kV (range
19–22 kV). Colour Doppler examinations were performed on a Siemens Sonoline G40 using a 3.75-MHz convex
transducer. In the study group, measurements were made in the renal interlobar
arteries before, first, second, seventh and
thirty days after ESWL. For renal stones,
measurements were made in the vicinity of the stones (nearby region), at a distance of at least 2 cm from the stones
(remote region) and in the contra lateral
kidney. Measurements were made when
three similar waves were registered sequentially. Measurements were repeated
three times for each region, and the RI
value recorded for each region was the
arithmetic mean of these three measurements. Vascular resistance was determined at an artery of renal parenchyma
with the help of pulsed wave Doppler ultrasound. To eliminate the problem of
angle correction the RI was calculated
by the equation: (systolic peak velocityend diastolic peak velocity) / systolic
peak velocity.
The paired t-test, a parametric test,
was used to compare RI values at 1,2,7
days and 30 days post-ESWL with preESWL values in the renal stones group.
The paired t-test was also used to compare RI values in the nearby and remote
regions with those in the contra lateral
kidney for the pre-ESWL measurement
and both post-ESWL measurements.
22 females(37%) with renal stones size
6-18mm, who underwent ESWL. Their
ages ranged from 22 to 55 years, with
mean ages of 42,3 years. Stones were
diagnosed by means of i.v. urography
(IVU), X-ray and ultrasonography. Patients with normal kidney function on
IVU and normal parenchyma echo on
ultrasonography were included in the
study. Patients with diabetes melli- 3. RESULTS
tus, renal parenchyma disease or uriMean blood pressure in patients with
nary system infections were excluded. renal stones was 118/79 mmHg before
Patients with hypertension (diastolic and 124/83 mmHg after ESWL. No sigblood pressure 90 mmHg and/or sys- nificant changes were found between
tolic blood pressure
140 mmHg) and patients receiving hypertensive therapy
were also excluded.
A mong pat ient s
with renal stones
(calyceal and pelvis renal stones),
those with ecstasies in the collecting system were excluded. ESWL was
performed using a
Siemens Multiline
2. MATERIALS AND METHODS
lithotripter. The avThe study group comprised 60 nor- erage number of Figure 1. Calculation of renal resistive index (RI) A peak systolic velocity; B
motensive patients 38 males(63%) and shock waves per pa- peak end diastolic velocity. RI=(A-B)/A
1. OBJECTIVES
Extracorporeal shock wave lithotripsy (ESWL) hase become a routine
methode for treatement of upper urinary tract stone disease. It is effective
and minimal invasive treatment for the
most urinary stones, but also with significant acute renal injuries and longterm complications (1,2,3). At present,
extracorporeal shock-wave lithotripsy
(ESWL) is used in the treatment of 90%
of all renal stones . Although its reliability and efficacy have been demonstrated, there are a number of studies
concerning post-ESWL complications
(4,5). However, major life-threatening
complications are rare in either the early
or late phase. Many techniques have
been used to investigate the effects of
ESWL on the kidneys, one of which involves measurement of the resistive index (RI) in the renal interlobar arteries
using Doppler, a non-invasive diagnostic
technique (6). In this study, colour Doppler ultrasonography was used to determine whether interlobar RI values were
affected in patients treated with ESWL
for renal stones.
MED ARH 2009; 63(3) • ORIGINALNI ČLANCI / ORIGINAL PAPERS
143
Effects of Extracorporeal Shockwave Lithotripsy on Renal Vasculature and Renal Resistive Index (RI)
Figure 2. Changes in resistive index (RI) in treated kidney. (Data were presented by mean ±SD 0,005)
pre- and post-ESWL means blood pressures. No correlation was found between
mean maximum voltage or average number of shock waves and changes in RI
at 1, 2,7days and 30 days post-ESWL.
In patients with renal stones, RI (mean
kidney before ESWL, there were, however, significant differences 1 day and 2
day after ESWL. There was also a significant difference 1 day after ESWL between RI values in the contra lateral kidney. RI was measured in all patients with
4. DISCUSSION
Resistive index
0,645
0,64
0,635
0,63
Resistive index
0,625
0,62
0,615
0,61
Before ESWL
1.day
2.day
7.day
30.day
Figure 3. Changes in resistive index (RI) in contra lateral-not treated kidney. (Data were presented by
mean ±SD 0,005)
±SD) in the nearby region was 0.62 ± renal stones 30 days after ESWL. There
0.05 before ESWL, increasing to 0.67 were no statistically significant differ± 0.05 at 1 day; to 0.66 ± 0.05 at 2 day ences between RI values in the nearby
and to 0,62 ± 0.05 at 7 day post-ESWL. or remote regions and those in the conBoth post-ESWL values first and second tra lateral kidney either before or 30 days
day were significantly different from the after ESWL. RI values in the nearby repre-ESWL values (p =0.001). RI was at gion and contra lateral kidney 1, 2 and
base line 30days after ESWL 0,62 ± 0,05. 7 days after ESWL did not differ signifThere was an increase in RI after ESWL icantly from those before ESWL. Howin the contra lateral
kidney. This difference
was significant at first
day after ESWL 0,64
± 0,05.
Di f ferences between pre- and postESWL values in the
contra lateral kidney
are shown in Fig.4.
There were no significant differences between RI in the nearby
or remote regions and Figure 4. Sequent changes in RI in ipsilateral and contra lateral kidney
in the contra lateral
144
ever, values recorded in the remote region 1 week after ESWL were not significantly higher than those recorded
before ESWL.
There was also no statistically significant difference in the contra lateral kidney between pre-ESWL and 2,7 and 30
days post-ESWL values (p > 0.05), but
there was a significant difference between pre-ESWL and 1 day post- ESWL
values 0,64 ± 0,05. No significant difference in RI values was determined in the
ipsilateral and contra lateral kidneys before and 2,7 days and 30 days after the
ESWL procedure in patients with renal
stones (p > 0.05). RI was measured in all
patients with renal stones 30 days after
ESWL; there was no statistically significant difference between these values and
pre-ESWL values in either the ipsilateral
or contra lateral kidney.
MED ARH 2009; 63(3) • ORIGINALNI ČLANCI / ORIGINAL PAPERS
The safety and efficacy of ESWL has
been proved by a number of studies investigating acute renal injuries from
ESWL by various techniques (7,8,9,10).
ESWL has been used since the 1980s
for the treatment of urolithiasis, and its
efficacy and reliability have been established. A number of methods have been
used to investigate post-ESWL changes
in the kidney, including IVU, ultrasonography, CT, MRI, radionucleide renography and serum and urine analyses. Although complications necessitating surgery, such as hematoma, are rare,
MRI studies have revealed post-ESWL
change rates as high as 74%. In studies
of the effects of ESWL on renal RI using
Doppler ultrasonography, a non-invasive
method, measurements have been made
at different times post-ESWL (11,12,13).
The present study demonstrated that
the RI of treated kidneys significantly increased after ESWL. As result of cellular
infiltration and oedema formed around
the peripheral branches of renal arteries,
perivascular tissue thickening may occur and vascular resistance may therefore increase (14,15).
In the present study, we found increased RI values at least 2 cm from the
stones at 1 day and 2 day post-ESWL on
ipsilateral kidney and 1.day on contra lateral kidney. Interestingly, although there
was no difference between pre-ESWL
and 7 days and 30 days post-ESWL values in the nearby region and the contra
lateral kidney.
Effects of Extracorporeal Shockwave Lithotripsy on Renal Vasculature and Renal Resistive Index (RI)
5. CONCLUSION
The RI has proved to be a sensitive
tool for monitoring vascular and tubulointestinals diseases of the kidney. It is
widely used to detect intrarenal oedema,
which occurs transplant rejection, acute
tubular necrosis and obstructive pyelocaliectasis. In all conditions RI levels
greater than 0,7 are considered to indicate pathologic change.
In conclusion, there is a temporary
increase in RI values in the first and
second day following ESWL in the ipsilateral kidneys, which is most marked
in the region near the renal stones. RI
in contra lateral kidney is most market
first day following ESWL. RI values return to normal within 7 day and 30 day
after ESWL in ipsilatreal kidney and for
contra lateral kidney RI values returns
to base line 2 day post ESWL. ESWL did
not indicate pathological RI changes in
treated and non treated kidney.
REFERENCES
3. 4. 5. 6. 7. 8. 9. 1. Aoki Y, Ishitoya S, Okubo K, et al. Changes 10. in resistive index following extracorporeal shock wave lithotripsy. Int J Urol,
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2. Villanyi KK, Szekely JG, Farkas LM, et al.
Short-term changes in renal function af- 11. ter extracorporeal shock wave lithotripsy
in children. J Urol, 2001;166:222-4.
Karlsen SJ, Berg KJ. Acute changes in kidney function following extracorporeal
shock wave lithotripsy for renal stones. Br
J Urol, 1991;67:241-5.
Knapp PM, Kulb TB, Lingeman JE, et al.
Extracorporeal shock wave lithotripsyinduced perirenal hematomas. J Urol,
1988;139:700-3.
Knapp R, Frauscher F, Helweg G, et al. Agerelated changes in resistive index following extracorporeal shock wave lithotripsy.
J Urol 1995;154:955-8.
Ulrich JC, York JP, Koff SA. The renal vascular response to acutely elevated intrapelvic pressure: resistive index measurements in experimental urinary obstruction. J Urol, 1995;154:1202-4.
Williams CM, Kaude JV, Newman RC, et
al. Extracorporeal shock-wave lithotripsy:
long-term complications. AJR Am JRoentgenol, 1988;150:311-5.
Webb JA. Ultrasonography and Doppler
studies in the diagnosis of renal obstruction. BJU Int,2000;86(Suppl 1):25-32.
Dodd GD, Kaufman PN, Bracken RB. Renal arterial duplex Doppler ultrasound
in dogs with urinary obstruction. J Urol,
1991;145:644-6.
Willis LR, Evan AP, Connors BA, et al.
Relationship between kidney size, renal
injury, and renal impairment induced by
shock wave lithotripsy. J Am Soc Nephrol,
1999;10:1753-62.
Beduk Y, Erden I, Gogus O, et al. Evalu-
ation of renal morphology and vascular
function by color flow Doppler sonography
immediately after extracorporeal shock
wave lithotripsy. J Endourol, 1993;7:45760.
12. Newman R, Hackett R, Senior D, et al.
Pathologic effects of ESWL on canine renal tissue. Urology, 1987;29:194-200.
13. Nazaroglu H, Akay A. Ferruh, Bükte Yasar,
Sa h i n Hay ret t i n et a l l . S c a nd i n avian journal of urology and nephrology 2003, vol. 37. 408-2. 14. Karadeniz T, Topsakal M, Eksioglu A, et al.
Renal hemodynamics in patients with obstructive uropathy evaluated by color Doppler sonography. Eur Urol, 1996;29:298301.
15. Kaude JV, Williams CM, Millner MR, et
al. Renal morphology and function immediately after extracorporeal shockwave lithotripsy. AJR Am J Roentgenol,
1985;145:305-13.
16. Shokeir AA, Nijman RJ, el-Azab M, et al.
Partial ureteral obstruction: role of renal
resistive index in stages of obstruction and
release. Urology, 1997;49:528-35.
Corresponding author: Ass prof Mustafa
Hiros, MD, PhD. Urology clinic. Clinical center
of Sarajevo University. Bolnicka 25. E-mail:
m.hiros@bih.net.ba
MED ARH 2009; 63(3) • ORIGINALNI ČLANCI / ORIGINAL PAPERS
145
Aerozagađenje i trend hospitalizacije djece zbog bronhoopstrukcije na području Tuzlanskog kantona
Aerozagađenje i trend hospitalizacije
djece zbog bronhoopstrukcije na
području Tuzlanskog kantona
Air Pollution and Hospital Admission Trends of Children with
Bronchial Obstruction in Tuzla Canton
Devleta Hadžić¹, Nada Mladina¹, Farid Ljuca2, Mustafa Bazardžanović2
Klinika za dječije bolesti, Univerzitetski klinički centar Tuzla, Bosna i Hercegovina1
Zavod za fiziologiju, Medicinski fakultet Univerziteta u Tuzli, Bosna i Hercegovina2
Klinika za urologiju, Univerzitetski klinički centar Tuzla, Bosna i Hercegovina3
Originalni članak
SAŽETAK
Prevalenca bronhoopstrukcije kod djece je u stalnom porastu u svim uzrasnim kategorijama i po globalnim
podacima. Brojne studije dovode u vezu stalni porast respiratornih oboljenja i aerozagađenje. Cilj ovog rada
bio je da se istraži moguća povezanost trenda hospitalizacije djece zbog bronhoopstrukcije i visine izmjerenih
koncentracija polutanata aerozagađenja na području Tuzlanskog kantona. Rezultati istraživanja pokazali su da
je distribucija bolnički liječene djece zbog bronhoopstrukcije u posmatranom jednogodišnjem periodu bila
različita u odnosu na mjesto stanovanja i sezonu. Prostorna distribucija pokazala je najveću zastupljenost pacijenata iz Tuzle, Lukavca i Živinica. Procenat liječene djece iz ovih općina bio je značajno iznad procenta koje su
ove općine zauzimale u ukupnoj populaciji. Sezonska distribucija bolnički liječene djece zbog bronhoopstrukcije
statistički značajno se razlikovala u dvije posmatrane grupe općina i u dva perioda sezone grijanja. Polutanti
aerozagađenja, sumpordioksid i taložna prašina, bili su značajno viših vrijednosti u sezoni grijanja u odnosu
na sezonu bez grijanja. Utvrđena je povezanost između trenda hospitalizacije djece zbog bronhoopstrukcije i
visine izmjerenih polutanata aerozagađenja.
Ključne riječi: bronhoopstrukcija, trend hospitalizacije, aerozagađenje, dječija dob.
Original paper
SUMMARY
The prevalence of bronchial obstruction in children is continuously increasing at any age. Many studies have
found associations between increase of respiratory diseases and air pollution. The aim of this paper was to establish possible connection between children hospital admission trends for bronchial obstruction and levels of
measured concentration of air pollution agents in Tuzla Canton area. The results of investigation demonstrated
that the distribution of hospital admissions of children with bronchial obstruction was different regarding place
of inhabitants and season. Spatial distribution demonstrated that the highest number of children treated for
bronchial obstruction was from Tuzla, Lukavac and Živinice. The incidence of patients from these municipalities was significantly above the participation of these municipalities in total population. Seasonal distribution
of hospital admissions of children with bronchial obstruction was different for single municipalities of Tuzla
Canton and for different seasons. Air pollutants, sulfur oxide and dust deposition were significantly higher for
heating season compared to season without heating. There is a link between frequency of hospital admission
for bronchial obstruction and level of measured air pollutants.
Key words: bronchial obstruction, hospital admission trends, air pollution, childhood
1. UVOD
Prevalenca bronhoopstrukcije kod
djece u stalnom je porastu u svim uzrasnim kategorijama i po globalnim podacima (1). Prema većini istraživanja,
oko 50% djece ima barem jednu epizodu
bronhoopstrukcije u prvih 6 godina života (2). Genetska predispozicija ima neosporan značaj, a izloženost određenim
okolinskim faktorima u ranom djetinjstvu može ubrzati nastanak ranih simptoma (1, 2). Brojne studije izvještavaju
o porastu prevalence bronhoopstrukcije kroz trend prvih hospitalizacija, od
kojih i do 75% su djeca ispod 4 godine,
a preko 60% dječaci (3). Većina autora
govori o značajnom opadanju ponovnih hospitalizacija, što se pripisuje unapređenju liječenja (4, 5). Sezonske varijacije trenda hospitalizacije djece zbog
146
bronhoopstrukcije bilježe porast broja
liječenih najčešće u jesen i zimu, a u većini studija najmanji broj liječenih bilježi
se u ljetnjim mjesecima (6, 7, 8). Autori
to objašnjavaju sezonskim varijacijama
uvjeta okoline, kao što su aerozagađenje i sezonske virusne infekcije. Studije
koje izvještavaju o geografskim varijacijama incidence i prevalence respiratornih oboljenja, razlike u učestalosti respiratornih oboljenja za pojedina područja
vezuju uz ambijentalne uvjete sredine,
prije svega nivo aerozagađenja (9, 10).
Brojne studije dovode u vezu stalni
porast respiratornih oboljenja i aerozagađenje. Izloženost polutantima aerozagađenja (taložna prašina, sumpor dioksid, azotdioksid i ozon) i njen efekat na
zdravlje bila je predmet istraživanja brojnih epidemioloških studija (9, 10, 11, 12,
MED ARH 2009; 63(3) • ORIGINALNI ČLANCI / ORIGINAL PAPERS
13). Značajno veća prevalenca bronhitisa i perzistentnog kašlja, posebno kod
mlađe djece i češće kod dječaka, dovodi
se u pozitivnu povezanost sa izmjerenim nivoom taložne prašine kao polutanta aerozagađenja (14). Značajan porast prijema u bolnicu kod djece zbog
respiratornih oboljenja u svim starosnim grupama, gdje dominira pneumonija i bronhitis kod djece mlađe od 4 godine, a astma kod djece u grupi 5-14 godina, dovodi se u vezu sa izmjerenim nivoom polutanata aerozagađenja, taložne
prašine, azotdioksida i sumpordioksida
(15). Većina studija istražuje aerozagađenje uzrokovano saobraćajem (16, 17, 18 ).
Tuzlanski kanton je najveći kanton u
Federaciji Bosne i Hercegodine. Površine
je 2792 km2 što čini 10,6 % ukupne površine Federacije, i ima 611 000 stanovnika što je 26 % ukupnog stanovništva
Federacije (19). Od toga 91 491 čine djeca
uzrasta do 15 godina. Tuzlanski kanton
ima najveću gustinu naseljenosti u Bosni
i Hercegovini, koja iznosi 203 stanovnika
na km2, što je dvostruko više od presjeka
Bosne i Hercegovine. Smatra se najzagađenijim kantonom Bosne i Hercegovine
(19). Sva toplotna i električna energija u
Tuzlanskom kantonu dobija se sagorijevanjem fosilnih goriva, i to uglavnom
uglja, koji u ovom području sadrži visok
procenat sumpordioksida (19).
Na području Tuzlanskog kantona
2003. godine uspostavljen je Sistem za
praćenje kvaliteta zraka kojim se vrši
automatski monitoring koncentracije
osnovnih pokazatelja kvaliteta zraka i
meteoroloških podataka. Sistem se sastoji od pet fiksnih i jedne mobilne imisione stanice, koje su opremljene mjernim
uređajima za mjerenje koncentracija pet
polutanata aerozagađenja (sumpordioksid, azotdioksid, ozon, ugljenmonoksid
i taložna prašina); meteoroloških podataka (temperatura zraka, brzina vjetra,
pravac vjetra, pritisak, sunčevo zračenje
i količina padavina), te centralne jedinice
(server) za prikupljanje, pohranjivanje
i obradu rezultata mjerenja. Vođenje i
održavanje Sistema za praćenje kvaliteta
zraka i informiranje javnosti o kvalitetu
zraka je u nadležnosti Ministarstva prostornog uređenja i zaštite okolice i provodi se u skladu sa Zakonom o zaštiti
zraka, Pravilnikom o graničnim vrijednostima kvaliteta zraka i Pravilnikom o
monitoringu kvaliteta zraka Federacije
Bosne i Hercegovine, te u skladu sa međunarodnim ugovorima. Prema Izvještaju za 2006. godinu (20) Tuzla, Luka-
Aerozagađenje i trend hospitalizacije djece zbog bronhoopstrukcije na području Tuzlanskog kantona
Ukupno
30,0
Bolesno
25,0
20,0
20,6
18,7
15,0
11,6 11,5
10,0
11,3
8,8 8,8
8,3
5,0
10,9
8,8
7,3
3,5
0,8
3,8
3,42,7
1,81,5
2,72,3
3,2
2,3
2,7
5,05,0
ić
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j
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ad
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ok
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ik
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ić
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ra
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Grafikon 1. Distribucija ukupne i populacije liječene djece uzrasta do 6 godina prema općini stanovanja
izložene aerozagađenju, jer je pritisak na
U periodu od 01. 01. 2006. do 31. kvalitet zraka u promatranom razdoblju
12. 2006. u Odjeljenju intenzivne njege uglavnom dolazio iz izvora sa područja
i terapije 332 pacijenata su liječena ove tri općine; istraženi su zbirni podaci
zbog bronhoopstrukcije. Od toga 208 za tri vodeće općine : Tuzla, Lukavac i Žisu bili dječaci (63 %), a 124 djevojčice vinice (općine Grupe jedan) i upoređeni
(37%). Prosječna starosna dob iznosila sa zbirnim podacima za ostale općine
je 3,06±3,22 godine. Od 332 pacijenta Tuzlanskog kantona - općine Grupe dva.
254 (76,5 %) bilo je mlađe od pet godina. Procenat liječene djece iz općina Grupe
Prostorna distribucija uzorka po- jedan (Tuzla, Lukavac i Živinice) bio je
kazala je najveći udio pacijenata iz Tu- daleko iznad procenta koje su ove općine
zle, Lukavca i Živinica.
Prostorna distribucija 70,0
63,0
Ukupno
Bolesno
59,5
liječene djece izražena 60,0
procentualno upore- 50,0
40,5
đena je sa prostornom
40,0
distribucijom ukupne
27,0
populacije djece Tu- 30,0
zlanskog kantona za 20,0
uzrast do 6 godina, 10,0
prema demografskim
0,0
podacima važećim za
Grupa 1
Grupa 2
period istraživanja. U
dobnoj skupini do 6 go- Grafikon 2. Udio ukupne i populacije liječene djece do 6 godina u
dina bilo je 80 % uku- dvije posmatrane grupe općina prema stepenu aerozagađenja općina
pnog uzorka liječene stanovanja (p<0,0001)
djece zbog bronhoop70
strukcije (grafikon 1).
60
Procenat liječene
djece iz Tuzle i Lukavca
50
bio je daleko iznad procenta koje su ove općine
40
imale u ukupnoj populaciji djece do 6 godina.
30
S obzirom da se različita učestalost u razli20
čitim geografskim po10
dručjima vezuje uz ambijentalne uvjete sre0
dine, prije svega nivo
0
2
4
6
8
10
12
14
aerozagađenja i s obziMjesec
rom da su Tuzla, Luka- Grafikon
3.broja
Korelacija
Slika . Korelacija
oboljelihbroja
tokomliječene
godine djece i sezone. Broj liječene djece
P=0,009
vac i Živinice ocijenjene se
značajno povećava u zimskim mjesecima (p<0,009)
Broj oboljelih se značajno povećava u zimskom periodu
kao općine posebno
3. REZULTATI RADA
Broj oboljelih
Analiza se bazirala na populaciji pacijenata liječenih zbog bronhoopstrukcije u Odjeljenju intenzivne njege Klinike za dječije bolesti u Tuzli u periodu
od 01. 01. 2006. do 31.12. 2006. godine.
Svi odabrani pacijenti bili su sa područja
Tuzlanskog kantona. Izvor podataka za
ovo istraživanje bili su Protokoli prijema
u Kliniku za dječije bolesti i Protokol
Odjeljenja intenzivne njege Klinike za
dječije bolesti, kao i historije bolesti liječene djece. Istražen je trend hospitalizacije djece zbog bronhoopstrukcije
u odnosu na dob, spol, mjesto stanovanja i sezonu. U istraživanju je korištena
i druga baza podataka dobijena iz aktuelnog Izvještaja Ministarstva prostornog uređenja Vlade Tuzlanskog kantona o kvalitetu zraka na području Tuzlanskog kantona sa mjernih stanica Sistema za praćenje kvaliteta zraka za period koji obuhvata istraživanje (20). Praćene su maksimalne, minimalne i prosječne dnevne vrijednosti pet pokazatelja kvaliteta zraka: sumpordioksida,
azotdioksida, ugljenmonoksida, ozona
i taložne prašine sa pet fiksnih mjernih
imisionih stanica i jedne mobilne imisione stanice. Općine Tuzla, Lukavac i Živinice, u ovom Izvještaju ocijenjene kao
općine posebno izložene aerozagađenju,
označene kao općine Grupe jedan. Analizirani rezultati za ove općine upoređeni
su sa zbirnim podacima za ostale općine
Tuzlanskog kantona koje su u istraživanju označene kao općine Grupe dva. U
statističkoj obradi podataka korištene
su standardne metode deskriptivne statistike (mjere centralne tendence, mjere
disperzije). Za testiranje značajnosti razlika medju uzorcima korišteni su parametarski i neparametarski testovi signifikantnosti (X²-test, Studentov t-test)
kao i metoda linearne korelacije. Statističke hipoteze su testirane na nivou
signifikantnosti od α = 0,05, tj. razlika
među uzorcima smatra se značajnom a
koje p < 0,05.
32,8
Lu
2. ISPITANICI I METODE RADA
35,0
Tu
vac i Živinice ocijenjene su kao općine
posebno izložene aerozagađenju, jer pritisak na kvalitet zraka u promatranom
razdoblju uglavnom je dolazio iz izvora
sa područja ove tri općine.
Cilj ovog rada bio je da se istraži
moguća povezanost trenda hospitalizacije djece zbog bronhoopstrukcije tokom
2006. godine i visine izmjerenih koncentracija polutanata aerozagađenja na području Tuzlanskog kantona.
MED ARH 2009; 63(3) • ORIGINALNI ČLANCI / ORIGINAL PAPERS
147
Aerozagađenje i trend hospitalizacije djece zbog bronhoopstrukcije na području Tuzlanskog kantona
25,0
Grupa 1
22,8
Grupa 2
20,0
18,5
15,0
13,8
12,9
12,3
10,9
9,2
10,0
7,97,7
6,9
5,0
3,5
2,3
7,4
7,9
5,4
4,5
7,9
5,4
4,0
2,3
4,6
3,5
4,6
ba
r
ba
r
ec
em
D
r
r
ov
em
ba
N
O
kt
o
m
ba
pt
e
gu
st
Se
Au
Ju
li
i
Ju
n
M
aj
ril
Ap
t
M
ar
r
br
ua
Fe
Ja
n
ua
r
0,0
Grafikon 4. Sezonska distribucija liječene djece u dvije grupe općina
imale u ukupnoj populaciji djece do 6 godina. U općinama Grupe dva (ostale općine Tuzlanskog kantona) bio je značajno
manji procenat liječene djece u odnosu
na procenat koji su ove općine imale u
ukupnoj populaciji djece do 6 godina za
područje Tuzlanskog kantona prema demografskim podacima važećim za period istraživanja. Razlika među grupama
označena je statistički značajnom sa p <
0,0001 (grafikon 2).
Broj djece liječene u Odjeljenju intenzivne njege zbog bronhoopstrukcije
bio je različit tokom godine i po mjesecima. Najveći broj djece zabilježen je u
mjesecu decembru, a najmanji u julu i
augustu. Na sljedećem grafikonu prikazana je korelacija broja liječenih pacijenata i sezone. Broj liječenih se značajno povećavao u zimskom periodu sa
p<0,009 (grafikon 3).
Sezonska distribucija hospitalizacije
djece zbog bronhoopstrukcije istražena
je u dvije posmatrane grupe općina Tuzlanskog kantona: Grupa jedan (Tuzla,
Lukavac i Živinice) i Grupe dva (ostale
općine Tuzlanskog kantona). Sezonski
trend hospitalizacije bio je različit u dvije
posmatrane grupe općina (grafikon 4).
Broj liječene djece iz općina Grupe
jedan (Tuzla, Lukavac i Živinice ) bio je
veći u odnosu na broj liječene djece iz
općina Grupe dva (ostale općine Tuzlanskog kantona) tokom većeg dijela godine.
Uočena su dva sezonska perioda tokom
kojih je bio veći broj liječene djece iz općina Grupe jedan. To su bili periodi od
januara do aprila, te period od oktobra
do decembra. Broj liječene djece iz općina Grupe dva (ostale općine Tuzlan148
13,8
zirane djece u dvije posmatrane grupe
općina. Postojale su razlike u broju liječene djece iz općina Grupe jedan u
dva sezonska perioda. U sezoni grijanja bilo je značajno više liječene djece
iz općina Grupe jedan u odnosu na period bez grijanja. Razlika u broju liječene
djece u dva sezonska perioda za općine
Grupe jedan označena je statistički značajnom (p<0,0001). U općinama Grupe
dva nije postojalo značajno odstupanje
u broju hospitalizirane djece u dva sezonska perioda.
U istraživanju su analizirani maksimalne, minimalne i prosječne dnevne
vrijednosti pet pokazatelja kvaliteta
zraka, sumpordioksida, azotdioksida,
ugljenmonoksida, ozona i taložne prašine na području Tuzlanskog kantona za
period koji obuhvata istraživanje. Od pet
pokazatelja kvaliteta zraka prekoračenje
dozvoljenih vrijednosti zabilježena su za
sumpordioksid i taložnu prašinu, a prekoračenja dozvoljenih vrijednosti za ova
dva polutanta aerozagađenja zabilježena
tokom posmatranog jednogodišnjeg perioda, bila su u mjesecima koji odgovaraju sezoni grijanja. Upoređene su izmjerene prekoračene vrijednosti sumpordioksida i taložne prašine u dva sezonska
perioda: u sezoni grijanja i sezoni bez
grijanja (grafikon 6).
U sezoni grijanja zabilježen je zna-
skog kantona) bio je veći u odnosu na
broj liječene djece iz općina Grupe jedan
(Tuzla, Lukavac i Živinice) tokom jednog
sezonskog perioda: u periodu od maja do
septembra. Primijećena prostorna i sezonska razlika trenda hospitalizacije slagala se sa uobičajenim periodima sezone
grijanja. U toku uobičajene sezone bez
grijanja od maja do septembra, zabilježen
je veći broj liječene djeca iz općina Grupe
dva (ostale općine Tuzlanskog kantona).
U sezoni grijanja, od oktobra do decembra i od januara do aprila zabilježen je
veći broj liječene djece
160
iz općina Grupe jedan
Grijanje
Bez grijanja
140
(Tuzla, Lukavac i Živi120
nice) u odnosu na broj
100
liječene djece iz općina
80
Grupe dva.
60
Trend hospitaliza40
cije djece zbog bronho20
opstrukcije u odnosu
0
na grupe općina i na seGrupa 1
Grupa 2
zonu grijanja prikazan
GRAFIKON 5. Broj liječene djece u dvije sezone (sa i bez grijanja) u
je na grafikonu 5.
U sezoni grijanja dvije posmatrane grupe općina (p<0,0001)
bio je značajno veći broj
hospitalizirane djece
iz općina Grupe jedan 60
(Tuzla, Lukavac i Živi- 50
nice) u odnosu na op40
ćine Grupu dva (ostale
općine Tuzlanskog kan- 30
tona). Razlika među 20
grupama označena je
statistički značajnom 10
(p<0,0001). U periodu
0
Bez grijanja
bez grijanja nije posto- Grijanje
jalo značajno odstupa- GRAFIKON 6. Procenat dana sa prekoračenim razinama sumpor
nje u broju hospitali- dioksida i taložne prašine u dva sezonska perioda (p<0,0001)
MED ARH 2009; 63(3) • ORIGINALNI ČLANCI / ORIGINAL PAPERS
134
84
75
61
53,8
SO2
Prašina
16,5
2,7
0,0
Aerozagađenje i trend hospitalizacije djece zbog bronhoopstrukcije na području Tuzlanskog kantona
čajno veći procenat dana sa prekoračenim vrijednostima koncentracije sumpordioksida (53,8 %) u odnosu na sezonu
bez grijanja (2,7 %). Razlika izmjerenih
vrijednosti u sezonama sa i bez grijanja
bila je statistički značajna (p<0,0001). U
sezoni grijanja zabilježen je značajno veći
procenat dana sa prekoračenim vrijednostima koncentracije taložne prašine
(16,5%) u odnosu na sezonu bez grijanja
(0 %). Razlika izmjerenih vrijednosti u
dva posmatrana sezonska perioda bila
je statistički značajna (p<0,0001).
Najveći procent izmjerenih prekoračenih vrijednosti polutanata aerozagađenja zabilježen je u mjesecu decembru. U
istom periodu zabilježen je najveći procenat hospitalizirane djece zbog bronhoopstrukcije. Od ukupnog uzorka petina
je hospitalizirana tokom mjeseca decembra, a trećina od tog broja bili su pacijenti
iz Tuzle. Analizirano je dnevno kretanje
koncentracije polutanata aerozagađenja
i trend hospitalizacije zbog bronhoop-
3,5
Zagadjenost
3
2,5
2
1,5
1
0,5
0
1
2
3
4
5
6
7
8
9
10 11 12
13 14 15
16 17 18 19
20 21 22 23
24 25 26 27
28 29 30 31
Grafikon 7. Odnos prekomjernog aerozagađenja i broja hospitalizirane djece
ak godina. Neizbježno je spomenuti Londonsku epizodu iz decembra 1952. godine (21) kada je visoko aeorozagađenje
imalo poguban efekat na porast mortaliteta sedmicama nakon
Ima
toga perioda. Ova epizoda je značajna, jer je
ukazala na nedvosmislenu uzročnu povezanost. Povećan mortalitet nije zabilježen
u drugim područjima,
niti u periodima bez
aerozagađenja, iako su
ostali klimatski uvjeti
bili gotovo isti. Mortalitet je bio povišen u fazama visokog aerozaNema
0
1
2
3
gađenja i počeo je opaBroj djece
dati kada je aerozagađeGrafikon 8. Korelacija prisustva prekomjernog aerozagađenja i broja
nje opadalo. Dojenačka
hospitalizirane djece iz Tuzle ( r = -0,394 ; p = 0,046 )
smrtnost u tom periodu
bila je dvostruka.
strukcije djece iz Tuzle. Rezultati su priGeneralno se pacijenti dječijeg uzrakazani na grafikonu 7.
sta smatraju podložnijim i vulnerabilniRezultati ove analize pokazali su da
jim na štetne efekte aerozagađenja (13,
je nakon nekoliko uzastopnih dana sa iz14, 22). Većina studija potvrđuje znamjerenim prekoračenim vrijednostima
čajnu povezanost aerozagađenja i porepolutanata aerozagađenja , u narednim
mećaja plućne funkcije u djece (13, 23,
danima dolazilo do značajnog porasta
24, 25). Nedavne studije izvještavaju da
broja hospitalizirane djece zbog bronje prenatalna izloženost prevelikom aehoopstrukcije.
rozagađenju povezana sa ranom fetalKorelacija trenda prekomjernog aeronom smrti, prematuritetom i nižom tjezagađenja i trenda hospitalizirane djece
lesnom masom na rođenju (26, 27). Tazbog bronhoopstrukcije na području Tukođer postoje studije koje izvještavaju o
zle bila je statistički značajna sa r= -0,394
povezanosti aerozagađenja i porasta doi p<0,046 (grafikon 8).
jenačke smrtnosti (28, 29, 30). Efekti aerozagađenja u djece mogu biti različiti
4. DISKUSIJA
u odnosu na odrasle za iste vrijednosti
Uticaj aerozagađenja na zdravlje
vanjskih koncentracija pojedinih polutapredmet je brojnih studija zadnjih 50nata aerozagađenja (13). To se posebno
Zagadjenost
Broj djece
odnosi na ozon, koji je produkt fotohemijske reakcije u atmosferi, tako da pokazuje jake sezonske i dnevne varijacije:
Povišen je ljeti i poslijepodne, a nizak je
zimi, noću i rano ujutro. Unutrašnji prostori, naročito klimatizirani, smatraju se
zaštićenim. Suprotno tome, taložne čestice, posebno finije, prodiru u unutrašnje prostore i ne podliježu hemijskim
promjenama kao ozon ili sumpordioksid (31). Ljetnje epizode aerozagađenja i
efekti na zdravlje vezuju se za ozon; a u
epizodama zimskog aerozagađenja pogoršanje kliničkih simptoma i plućne
funkcije u djece sa astmom vezuje se za
nivo taložnih čestica (13).
Dnevne varijacije polutanata aerozagađenja utiču na trend hospitalizacije zbog respiratornih bolesti. Najviše
se izvještava o pogoršanju astme, povećanoj incidenci bronhitisa i pneumonije (32, 33).
U našem istraživanju 76,5% hospitalizirane djece bilo je mlađe od 5 godina,
a 60 % bili su dječaci. Brojne studije daju
slične rezultate o dobnoj i spolnoj distribuciji hospitalizirane djece zbog bronhoopstrukcije (6, 34). Razlike u učestalosti respiratornih bolesti u različitim područjima uglavnom se vezuju uz ambijentalne prilike. Oyana i Rivers (9) objavili su 2005. godine rezultate istraživanja trenda hospitalizacije zbog bronhoopstrukcije pacijenata uzrasta od 0-18
godina za područje grada Bafalo i okoline. Rezultati su pokazali signifikantno
veći broj pacijenata iz istočnih dijelova
ovog područja u odnosu na zapadne dijelove što se objašnjava postojećim izvorima saobraćajnog, industrijskog i ostalog aerozagađenja. Eroshina i saradnici
MED ARH 2009; 63(3) • ORIGINALNI ČLANCI / ORIGINAL PAPERS
149
Aerozagađenje i trend hospitalizacije djece zbog bronhoopstrukcije na području Tuzlanskog kantona
(10) objavili su 2004. godine slične rezultate za područje Moskve i okoline. U našem istraživanju značajno veći broj hospitaliziranih bio je iz općina koje su evidentno bile više izložene aerozagađenju.
Brojne studije provedene u Evropi,
Americi i Australiji osamdesetih i devedesetih observirale su dnevni trend hospitalizacije zbog respiratornih bolesti u
poređenju sa dnevnim kretanjem nivoa
aerozagađenja i zabilježile o porast prijema u danima visokog aerozagađenja
(13, 35). Pope (32) je analizirao hospitalizaciju djece zbog respiratornih bolesti
u Utahu tokom 3 godine u vezi sa višemjesečnim prekidom rada čeličane, najvećeg zagađivača u tom području. Rezultati su pokazali da je za više od 50%
opao prijem djece u bolnicu zbog astme
i pneumonije u periodu u kojem je čeličana bila zatvorena i u kojem je aerozagađenje bilo niže. Narednih godina, nakon prekida štrajka, trend hospitalizacije je ponovo porastao. Susjedna područja, gdje čeličana nije imala uticaja,
nisu imala kolebanja nivoa aerozagađenja niti trenda hospitalizacije. U našem
istraživanju analiza dnevnih kolebanja
pet glavnih pokazatelja aerozagađenja
zabilježila je prekoračenje dozvoljenih
vrijednosti za sumpordioksid i taložnu
prašinu. Ova prekoračenja uglavnom su
bila u mjesecima koji odgovaraju sezoni
grijanja. Trend hospitalizacije pacijenata
slagao se sa stepenom izloženosti aerozagađenju. Glavni zagađivači na ovom
području su izvori toplotne i električne
energija koja u Tuzlanskom kantonu
potiče od sagorijevanja fosilnih goriva,
uglavnom uglja, koji sadrži visok procenat sumpordioksida.
Slično istraživanje proveli su Barnet
i saradnici (15) tokom tri godine u pet
velikih gradova Australije i Novog Zelanda, što čini preko 50 % ukupne populacije ovog regiona. Analizirana je povezanost aerozagađenja i trenda hospitalizacije djece zbog respiratornih oboljenja. Signifikantan porast hospitalizacije
djece zbog pneumonije i akutnog bronhitisa zabilježen je u dobnoj skupini od
0–5 godina; te astme u dobnoj skupini
od 5–14 godina. Ovaj porast bio je signifikantno povezan sa nivoom taložne
prašine, azotdioksida i sumpordioksida.
Postoje dokazi da reduciranje aerozagađenja ima povoljan efekat na zdravlje, reducira se broj hospitalizacija, broj
pogoršanja astme i drugih respiratornih
bolesti, te popravlja plućna funkcija ispitanika (32, 36, 37, 38). Osim spomenute
150
studije iz Utaha, postoji i novija studija
provedena u Atlanti tokom olimpijskih
igara, zbog kojih je saobraćaj u tom periodu bio planski reduciran. Rezultati
su pokazali opadanje epizoda pogoršanja astme u periodu reduciranog saobraćaja i aerozagađenja (36). Nedavna studija u Istočnoj Njemačkoj pokazala je da
redukcija aerozagađenja dovodi do smanjenja respiratornih bolesti i simptoma
u djece (37). Poboljšanje praćene plućne
funkcije evidentirano je u djece koja su
promijenila mjesto boravka i napustila
područja visokog aerozagađenja (38). Sve
ove studije imaju veliki značaj zbog evidentnog dokaza da intrvencija u pravcu
popravljanja ambijentalnih uvjeta ima
povoljne efekte na zdravlje.
7.
8.
9.
10.
5. ZAKLJUČCI
Trend hospitalizacije djece zbog
bronhoopstrukcije u Tuzlanskom kantonu imao je različitu sezonsku i prostornu distribuciju. Dominirala su djeca
uzrasta do 5 godina uz prednost dječaka.
Broj liječenih bio je statistički značajno
veći u zimskim mjesecima. Sezonski
trend hospitalizacije bio je različit za pojedine općine Tuzlanskog kantona i zavisno od sezone grijanja. Polutanti aerozagađenja, sumpordioksid i taložna prašina, bili su značajno viših vrijednosti u
sezoni grijanja u odnosu na sezonu bez
grijanja. Utvrđena je povezanost trenda
hospitalizacije djece zbog bronhoopstrukcije i dnevnih varijacija polutanata
aerozagađenja.
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Kontakt adresa autora: Dr. Devleta Hadžić,
Univerzitetski klinički centar Tuzla, Klinika za
dječije bolesti, Trnovac bb, 75000 Tuzla, Bosna
i Hercegovina, 00 387 35 303 713, e-mail:
devletahadzic@yahoo.com
MED ARH 2009; 63(3) • ORIGINALNI ČLANCI / ORIGINAL PAPERS
151
Uticaj statina na postoperativni tretman pacijenata operiranih radi ugradnje aortokoronarnih premoštenja
Uticaj statina na postoperativni
tretman pacijenata operiranih
radi ugradnje aortokoronarnih
premoštenja
Effects of Statins on Postoperative Treatment of Patients After
Aortocoronary Bypass Grafting
Mehmed Kulić1, Mirza Dilić2, Vjekoslav Gerc3, Bećir Heljić4
Kardiološki odjel, Centar za srce, Klinički centar Univerziteta u Sarajevu, Bosna i Hercegovina1
Klinika za angiologiju, Klinički centar Univerziteta u Sarajevu, Bosna i Hercegovina2
Klinika za bolesti srca i reumatizam, Klinički centar Univerziteta u Sarajevu, Bosna i Hercegovina3
Klinika za endokrinologiju i dijabetes, Klinički centar Univerziteta u Sarajevu, Bosna i Hercegovina4
Originalni članak
Sažetak
Cilj rada: Antiinflamatorni utjecaj hipolipemijskih lijekova, statina, kod pacijenata poslije ugradnje aortokoronarnih
premoštenja dosad nije istraživan. Cilj rada je pokazati utjecaj simvastatina na postoperativni tok, laboratorijske
nalaze i postoperativne perikardijalne izljeve kod pacijenata operiranih radi ugradnje aortokoronarnih premoštenja. Materijal i metode: U studiju je uključeno 80 pacijenata sa koronarnom arterijskom bolesti. Svi pacijenti su
podijeljeni u dvije grupe: ispitivanu grupu od 40 pacijenata sa koronarnom ishemijskom bolesti, operiranih radi
ugradnje aortokoronarnog premoštenja, koji su primali uobičajenu kardiohiruršku postoperativnu terapiju, uz
dodatak simvastatinske terapije u količini od 40mg. simvastatina dnevno, u periodu od 8. sata nakon extubacije
pacijenta do 14. postoperativnog dana, i kontrolnu skupinu od 40 pacijenata sa koronarnom ishemijskom bolesti,
operiranih radi ugradnje aortokoronarnog premoštenja tretiranih uobičajenom postoperativnom kardiohirurškom
terapijom. U radu su evaluirani demografski podaci, operativni izvještaji, laboratorijski postoperativni parametri,
te ehokardiografski pregledi tokom dvodnevnih postoperativnih perioda praćenja perikardijalnih izljeva. Podaci
su statistički evaluirani korištenjem statističkog programa SPSS. Parametrijski podaci bili su testirani Studentovim T-testom, dok su neparametrijski podaci obrađeni X² testom i proporcijama. Korišten je i Mann-Whitney U
test uz CI: 95% tj. nivo signifikantnosti p<0.05. Rezultati: Naše istraživanje je pokazalo da simvastatini u dozi od
40mg/24.h. djeluju efektno u postoperativnom periodu na smanjenje vrijednosti lipida i signifikantno smanjenje
postoperativnih perikardijalnih izljeva mjereno tokom dvodnevnog perioda u toku trećeg i četrnaestog postoperativnog dana (p<0.037, p<0.01). Zaključak: Statinska terapija u dozi od 40mg/24.h je u našoj studiji aplicirana bez
sporednih efekata i bez interakcija sa drugim postoperativno upotrebljenim lijekovima. Statini su pokazali dobar
antiinflamatorni učinak na ovako ograničenom broju pacijenata. Statinska terapija bi se, uz ostalu postopeartivnu terapiju, trebala obavezno nastavljati u ranom kardiohirurškom postoperativnom periodu. Antiinflamatorno
dejstvo statina potrebno je i dalje ispitivati, i to na mnogo većoj skupini pacijenata. O antiinflamatornom dejstvu
hipolipemika nema do sada velikih studija koje bi odagnale svaku sumnju u antiinflamatorno dejstvo hipolipemika. Posebno treba istaći da nema velikih studija koje bi istraživale antiinflamatorno dejstvo hipolipemika na
primjeru postperikardiotomnih perikardijalnih izljeva.
Ključne rijeći: simvastatin, aortokoronarno premoštenje, perikardijalni izljevi
Original paper
SUMMARY Aim: There are no previous data about the anti-inflammatory effects of hypolipemic agents, statins, in patients
after aortocoronary bypass grafting. The aim of this study was to demonstrate effects of simvastatine on
postoperative treatment, laboratory findings and pericardial effusion during postoperative period, in patients
after aortocoronary bypass grafting procedures. Material and methods: The study included 80 patients with
coronary arterial disease divided in two groups. The study group included 40 patients with coronary ischemic
disease subjected to surgical implantation of aortocoronary bypass graft who received standard cardio-surgical
postoperative treatment supplemented with 40 mg of simvastatine per day, starting at 8 hours after the patient’s
extubation until postoperative 14th day. The control group included 40 patients after aortocoronary bypass
grafting procedures with standard intensive postoperative treatment. Evaluation included demographic data,
surgical reports, postoperative laboratory parameters and echocardiography findings, taken during two days
monitoring of postoperative pericardial effusion. Statistical data analysis was conducted using SPSS software.
Parametric data were evaluated using Student T-test, while non-parametric data were processed using X2 test
and proportion analysis. Mann-Whitney U test was applied with CI of 95%, i.e. significance level p<0.05. Results:
No significant differences were found between the observed groups with regards to demographic data, number
of the implanted aortocoronary bypasses and postoperative laboratory parameters. However, the differences
in echocardiographically determined dimensions of postoperative pericardial effusions measured during two
days of postoperative observation (between the 3rd and the 14th day postoperative) were significant (p<0.037,
p<0.01). Conclusion: In our study, statin therapy consisting of 40 mg/24 hrs was applied with no side effects and
without interaction with the other postoperatively applied medications. Simvastatins, applied in the dosage of 40
mg/24 hrs, efficiently lead to significant reduction of postoperative pericardial effusions in postoperative period.
In this limited group of patients, statins have exhibited good anti-inflammatory effects. Statins with standard
therapy ought to be included in the early cardio-surgical postoperative period. Anti-inflammatory activities of
statins should be further investigation on much larger patient sample. So far, there is no record of a large study of
anti-inflammatory activities of hypolipemic agents that could waive the doubts into their effectiveness. It needs
to be stressed that no large studies of anti-inflammatory activities of hypolipemic agents in cases of postoperative
pericardial effusion were ever conducted. Keywords: simvastatine, aortocoronary bypass graft, pericardial effusion
152
MED ARH 2009; 63(3) • ORIGINALNI ČLANCI / ORIGINAL PAPERS
1. UVOD
Perikardiotomija je uobičajeni postupak kod svih kardiohirurških operacija, neophodan da bi se pristupilo
operativnom polju. Kod kardiovaskularnih pacijenata hirurška intervencija na perikardu u okviru operacije
aorto-koronarnog premoštenja izaziva
njegovu inflamatornu reakciju, koja se
u postoperativnim danima, kod nekih
pacijenata, izražava kao postoperativni
perikardijalni izljev. Uobičajeno se ova
reakcija događa u oko 10 do 40% pacijenata, pa sve do čak 64% operiranih
kardiohirurških pacijenata, češće kod
valvularnih, nego kod bolesnika sa koronarnom arterijskom bolesti (1).
2. CILJ RADA
Kod pacijenata poslije kardiohirurškog operativnog zahvata ugradnje
koronarnog arterijskog bypassa evaluirati utjecaj simvastatina u dozi od
40mg/24.h. u ranom kardiohirurškom
postoperativnom periodu od 8.h. poslije
intubacije do 14. postoperativnog dana.
3. METODE RADA
U radu su korištene sljedeće tehnike:
•• Lični i anamnestički podaci (ime,
prezime, godina rođenja, spol,
prethodno preležale bolesti).
•• Operativni izvještaj (vrsta urađene
kardiohirurške operacije, broj i vrsta ugrađenih aorto-koronarnih
premoštenja).
•• Klinički postoperativni pregled
(parametri RR i pulsa, te auskultatorni pregled srca i pluća, RTG
pluća i srca).
•• Laboratorijski nalazi (KS, ŠUK,
transaminaze, CK, urea i kreatinin,
holesterol i trigliceridi) prvog, trećeg, sedmog postoperativnog dana
i 14 dana nakon operacije.
•• Ehokardiografski pregled pacijenata, u cilju evaluacije postojanja,
veličine, lokalizacije i progresije razvoja postperikardiotomnog perikardijalnog izljeva i to:
•• Dvodnevni ehokardiografski pregledi u periodu od prvog postoperativnog dana do sedmog postoperativnog dana i to od dva kardiologa, kako bi se umanjila intraobserverska greška.
•• Ehokardiografska kontrola perikardijalnog izljeva na dan 14 to
dnevne, na isti način kao u prvim
periodima.
Svi dobijeni podaci su uzeti od paci-
Uticaj statina na postoperativni tretman pacijenata operiranih radi ugradnje aortokoronarnih premoštenja
jenata nakon što su informirani o vrsti
studije i njihovom učeću u njoj, i nakon
što su dali svoj pismeni pristanak za uzimanje terapije. Podaci su se prikupljali iz
pregleda dva kardiologa prospektivno u
periodu od 1 godine i to prema rednom
broju prijema pacijenta, tako su se pacijenti pod parnim brojevima prijemnog
protokola svrstavali u ispitivanu grupu
(grupu A), dok su oni pod neparnim brojem prijemnog protokola činili kontrolnu
grupu ili grupu B. Statinska terapija se
dodjeljivala pacijentima grupe A, tako,
da kardiolozi koji procijenjuju veličinu
postoperativno izraženog perikardijalnog izljeva ne znaju koji pacijenti primaju
statinsku terapiju, a koji ne.
Prospektivno dobijeni rezultati statistički su evaluirani korištenjem statističkog programa SPSS. Parametrijski podaci bili su testirani Studentovim
T-testom, dok su neparametrijski podaci
obrađeni X² testom i proporcijama. Korišten je i Mann-Whitney U test, uz CI:
95% tj. nivo signifikantnosti p<0.05.
4. REZULTATI RADA
Prosječna starost ispitanika iznosila je 57.g. +/- 8,36. Najmlađi ispitanika
imao je 42 godine, a najstariji 74 godina.
Nije bilo signifikantne razlike među grupama u odnosu na starost i spol pacijenata. Klinički je bila najzastupljeniji
simptom stabilne angine pectoris a bez
signifikantne razlike među grupama
(p=0.539). Nije postojala signifikantna
razlika među grupama u pogledu preoperativno ordinirane statinske terapije i
taj procenat je iznosio u ispitivanoj grupi
45% (18 pacijenata) na statinskoj terapiji, u odnosu na 47% (19 pacijenata) u
kontrolnoj grupi. Nije postojala signifikantna razlika među grupama u pogledu broja ugrađenih aortokoronarnih
premoštenja.
U poređenju laboratorijskih nalaza
nije bilo signifikantnosti među grupama
u odnosu na: Er, Le, ŠUK, CK, AST, ALT,
Ureu, kreatinin, holesterol i trigliceride.
Neinvazivna dijagnostika (Ehokardiografski podaci)
Prije evaluacije perikardijalnog izljeva odredili smo brojevima područja
ispred određenih zidova i veličinu perikardijalnih izljeva. Dobili smo signifikane razlike između ispitivane i kontrolne skupine u odnosu na parametar
postojanja ili odsustva postoperativnog
perikardijalnog izljeva. Ta se signifikan-
Lab.
Param.
ŠUK 1
ŠUK 2
ŠUK 3
ŠUK 4
CK 2
CK 3
CK 4
Lab.
Hol 1
Hol 2
Hol 3
Trig 1
Trig 2
Lab
AST 1
AST 2
AŠT 3
AŠT 4
ALT 1
ALT 2
ALT 3
ALT 4
Statini
Srednja
vrijednost
Broj
Std. Devijacija
Std. Greška
Da
40
6,105
1,812
,4292
Ne
40
6,012
1,641
,4286
Da
40
7,15
1,812
,444
Ne
40
7,87
1,765
,444
Da
40
6,367
3,538
,7008
Ne
40
6,213
1,813
,6944
Da
40
5,378
1,151
,3777
Ne
40
6,170
1,827
,3803
Da
40
90,55
42,94
10,895
Ne
40
83,22
44,89
10,902
Da
40
94,48
65,77
15,654
Ne
40
97,19
60,20
15,632
Da
40
94,48
65,77
8,834
Ne
40
82,24
40,46
8,874
broj
Srednja
vijednost
Statini
Std.
Devijacija
1,144
,3191
Ne
40
5,763
1,417
,3201
Da
40
3,862
,7100
,2091
Ne
40
4,125
,9608
,2101
Da
40
4,9733
,7757
,23177
Ne
40
4,9141
1,073
,23291
Da
40
2,2379
1,698
,34194
Ne
40
2,1613
,9398
,33912
Da
40
1,6485
,8109
,18179
Ne
40
1,5250
,6421
,18114
Std.
Devijacija
,520
,519
,672
,830
,390
,199
5,384
Srednja
vrijednost
,796
Sig.
(2-tailed)
40
Broj
,942
Std. Greška
Da
STATINI
Sig.
(2-tailed)
Std.
Greška
Da
40
23,15
8,610
2,870
Ne
40
24,44
13,97
2,890
Da
40
38,09
20,67
5,579
Ne
40
37,03
24,21
5,593
Da
40
32,27
9,847
3,135
Ne
40
29,41
14,98
3,155
Da
40
23,09
6,385
1,676
Ne
40
19,97
7,114
1,678
Da
40
34,82
23,66
5,289
Ne
40
33,84
18,58
5,269
Da
40
45,18
53,64
9,641
Ne
40
37,03
24,21
9,501
Da
40
31,64
11,44
3,604
Ne
40
28,94
17,13
3,625
Da
40
23,03
7,481
1,953
Ne
40
22,59
8,257
1,956
,152
,019
,234
,353
Sig.
(2-tailed)
,230
,274
,083
,488
,764
,092
,377
,802
Tabele 1, 2 i 3. Primjeri laboratorijskih parametara bez signifikantnih promjena.
tnost među skupinama u odnosu na postojanje ili otsustvo perikardijalnog izljeva i odnosila se na područja lateralnog zida LV-a i ispred apexa LV-a u svim
periodima praćenja, dok je za područje
ispred RV-a postojala signifikantnost u
drugom i trećem periodu praćenja. Podaci govore o signifikantnim razlikama
među grupama u odnou na postojanju
postoperativnih perikardijlnih izljeva
(p< 0,037, p< 0,001, p<0,0124).
MED ARH 2009; 63(3) • ORIGINALNI ČLANCI / ORIGINAL PAPERS
153
Uticaj statina na postoperativni tretman pacijenata operiranih radi ugradnje aortokoronarnih premoštenja
5. DISKUSIJA
U naše istraživanje uključeno je 80
ispitanika, podijeljenih u dvije skupine.
Prva ili ispitivana skupina sastojala se od
40 pacijenata, sa kardiovaskularnom bolešću operiranih radi ugradnje aortokoronarnog premoštenja (bypass-a), a koji
su postoperativno primali uz uobičajenu
postoperativnu kardiohiruršku terapiju i
40 mg. simvastatina jednom u 24.h. i to
počevši od osmog postoperativnog sata,
pa do posljednje kontrole, tj. do dana otpusta, odnosno, 7-10 dana nakon kardiohirurškog zahvata.
Druga kontrolna skupina sačinjena je
od 40 pacijenata sa kardiovaskularnom
bolešću, operiranih radi ugradnje aortokoronarnog bypass-a, koji su postoperativno primali uobičajenu postoperativnu
kardiohiruršku terapiju.
U grupama nije bilo signifikantnih
razlika, kako prema godinama, tako i
prema spolu. Osnovna tegoba koju su pacijenti osjećali je anginozna bol po stabilnom tipu u oko 65% pacijenata. Nije bilo
značajne razlike u vrsti i kvaliteti simptoma među pojedinim grupama.
Tako su vrijednosti hematokrita i
hemoglobina snižene na donje referentne granice, osobito u prvima postoperativnim danima, a kao posljedica kardiohirurškog perioperativnog krvarenja. Neposredno nakon operativnog zahvata kratkotrajno su bile povišene vrijednosti kreatin kinaze i CRP-a kao reakcija na oštećenje tkiva i posljedični
inflamatorni odgovor. Iz istog razloga u
tom periodu jako su povećane i transaminaze, dok su urea i kreatinin ostajali
u normalnim granicama ili su bili blago
povišeni. Nakon sedmog dana došlo je
do normalizacije svih navedenih vrijednosti laboratorijskih parametara u
obje skupine pacijenata, premda su pacijenti iz ispitivane grupe nastavljali da
uzimaju statinsku terapiju. Lipidogram
je bio u referentnim granicama, ali je
primjećen blagi pad razine holesterola
i triglicerida u periodima trećeg i sedmog postoperativnog dana, što se može
pripisati uz dejstvo statina i poremećenoj prehrani pacijenata u ranom postoperativnom periodu.
Broj ugrađenih bypass-a nije se razlikovao po pojedinim skupinama, a najviše
je bilo pacijenata sa ugrađena tri aortokoronarna bypass-a (63%) potom onih
sa dva (34%), dok su samo dva pacijenta
dobila jednostruki aortokoronarni bypass (3%).
Ehokardiografski pokazatelji su bili
154
od neobične su koriSrčani zid Veličina
Mann- Asymp. Sig
Statini
Broj
%
i period
izljeva
Whitney U (2-tailed)
sti jer je ehokardiografski pregled doNEMA
16
50,0
stupan na svakom
2-5mm
9
28,1
mjestu, lako primjeNE
PE 1-2 5-10mm
7
21,9
njiv, nije štetan za
pacijenta, može se
Ukupno
32 100,0
421,000
,109
ponavljati prema kliNEMA
23
68,8
ničkim i medicin2-5mm
6
12,5
skim potrebama, i
DA
PE 1-2 5-10mm
4
18,8
veoma je precizan
u odnosu na ocjenu
Ukupno
33 100,0
lokaliteta i veličine
postoperativnih peSrčani zid Veličina
Mann- Asymp. Sig
%
rikardijalnih izljeva. Statini
i period
izljeva Broj
Whitney U (2-tailed)
S t r at e g ij a vo NEMA
20
62,5
đenja neinvazivnih
2-5mm
7
21,9
ehokardiografskih
NE
PE 2-2 5-10mm
5
15,6
podataka mjerenja
postoperativnih peUkupno
32 100,0
rikardijalnih izljeva,
343,500
,001
NEMA
32
97,0
bila je usmjerena na
2-5mm
1
3,0
četiri područja, tj.
DA
PE
2-2
perikardijalni prostor ispred prednjeg
Ukupno
33 100,0
zida desnog ventrikula (1), ispred predSrčani zid Veličina
Mann- Asymp. Sig
%
njeg zida i apexa li- Statini
i period
izljeva Broj
Whitney U (2-tailed)
jevog ventrikula (2),
NEMA
28
87,5
i spred latera l nog
2-5mm
4
12,5
zida lijevog ventriNE
PE 3-2
kula (3), te ispod i iza
inferoposteriornog
Ukupno
32 100,0
miokardnog zida (4).
462,000
,037
NEMA
33 100,0
Drugi važan kriterij
bio je podjela na tri
DA
PE 3-2
različita perioda promatranja veličine peUkupno
33 100,0
rikardijalnog izljeva.
Ovim oznakama je
Srčani zid i Veličina
Mann- Asymp. Sig
%
dodana i brojevna Statini
period
izljeva Broj
Whitney U (2-tailed)
vrijednost postopeNEMA
13
39,4
rativnog perioda koji
2-5mm
18
54,5
su obuvatili prvi poNE
PE 4-2 5-10mm
2
6,1
stoperativni dan (1),
treći postoperativni
Ukupno
33 100,0
dan (2), sam dan ot423,000
,0124
NEMA
22
68,8
pusta, tj. obično 7.
2-5mm
4
12,5
do 10.postoperativni
DA
PE 4-2 5-10mm
6
18,8
dan (3).
Tako se u tabelama, kojima su poUkupno
32 100,0
kazivani podaci eho- Tabele 4, 5, 6 i 7 Primjeri ehokardiografske ocijene veličina
kardiografskog pra- postperikardiotomnih perikardijalnih izljeva drugog perioda praćenja (tj
ćenja perikardijal- trećeg postoperativnog dana)
nih izljeva nailazimo
na oznake PE (engl.
Npr. oznaka PE 2-2 značila je perikardiPericardial Effusion = Perikardijalni iz- jalni izljev ispred drugog zid, tj. ispred
ljev) 1-1, PE 2-1, PE 3-1, što se odnosi na prednjeg zida i apex-a lijevog ventrikula
zidove miokarda u prvom periodu pra- u drugom periodu praćenja, tj. trećeg poćenja, tj. prvog postoperativnog dana. stoperativnog dana.
MED ARH 2009; 63(3) • ORIGINALNI ČLANCI / ORIGINAL PAPERS
Uticaj statina na postoperativni tretman pacijenata operiranih radi ugradnje aortokoronarnih premoštenja
Imamo i oznake tri različita perioda
ehokardiografskih praćenja veličine perikardijalnih izljeva, tj. 1= prvi postoperativni dan, 2= treći do peti postoprativni dan, 3= dan otpusta (obično 7.-10.
dan). Veličina izljeva je mjerena u milimetrima i označavana simbolima koji su
značili: nema izljeva (0), trivijalni do mali
perikardijalni izljevi veličine do 5mm
(50-100ml izljeva, u našem radu oznaka
1), mali do umjereni izljev veličine od
5-10mm (govori o malom izljevu od 100200ml., u našem radu oznaka 2), umjereni do veliki izljevi veličine od 10-15mm
(250-500ml tekućine, oznaka 3), veliki
izljevi veličine 15-20mm (tj. ≥ 500ml,
oznaka 4), te izrazito veliki postperikardiotomni izljevi veličine > 20mm uz
znake kompresije (oznaka 5) (2).
Za ocjenu veličine perikardijalnih
izljeva nismo koristili druge radiološke
tehnike, kao npr. CT ili MRI, kako zbog
tehničkih poteškoća (dužina čekanja pretrage), tako i karakteristike ovih metoda
da uveličavaju aktuelnu veličinu izljeva
u odnosu na njihovu ehokardiografsku
procjenu (3).
Prvenstveno smo obratili pažnju na
parametar postojanja ili odsustva postoperativnog perikardijalnog izljeva i odnosa tih pokazatelja između ispitivane i
kontrolne skupine. Podaci pokazuju da
je postojala signifikantnost među skupinama u odnosu na postojanje ili odsustvo perikardijalnog izljeva u područjima lateralnog zida LV-a i ispred apex-a
LV-a u svim periodima praćenja, dok je
za područje ispred RV-a postojala signifikantnost u drugom i trećem periodu. Za
četvrti zid tj. iza i ispod LV-a nismo našli
signifikantnost u svezi sa traženim parametrima postojanja ili odsustva postperikardiotomnog perikardijalnog izljeva.
Navedene parametre smo prve pratili, jer
nam je najvažnije bilo, evaluirati broj pacijenata kod kojih uopće nije bilo izljeva.
Nakon toga evaluirali smo veličinu i
lokalizaciju postojećih postperikardiotomnih perikardijalnih izljeva. Pošto naša
studija obuhvata pacijente kod kojih postperikardiotomni perikardijalni izljevi
uobičajeno nisu jako izraženi (mnogo
su češći i obimniji kod pacijenata sa implantiranim vještačkim zaliscima, radi
postoperativno povećane upotrebe antikoagulantne terapije, nakon hirurgije
aortnog puta i transplantacije srca (4).
U grupama nismo imali velikih i izrazito velikih postperikardiotomnih perikardijalnih izljeva, tj. pronađeni izljevi
nisu prelazili granicu od 15-20mm.
Što se tiče signifikantnosti razlika u
nalazima kod ispitivane i kontrolne skupine, dobili smo podatke koji ukazuju da
je siginifikantna razlika među grupama
postojala u prvom periodu (prvi postoperativni dan) u područjima ispred vrha
lijeve komore i lateralnog zida, dok u
ovom periodu nije postojala signifikantna razlika područjima ispred RV-a i iza
i ispod LV-a. U drugom periodu signifikantnost je postojala u svim područjima, sem u području iza i ispod LV-a. U
trećem periodu praćenja imali smo istu
situaciju, da bi se potpuna nesignifikantnost podataka pokazala u četvrtom periodu, tj. mjeseca dana poslije kardiohirurškog zahvata. Analizirajući ove podatke uvidjeli smo da u radu ne postoji
signifikantnost ispred RV-a i iza LV-a.
Ova nesiginifikantnost se odnosi prije
svega na postoperativne kardiohirurške
postupke. Naime, odmah poslije kardiohirurškog zahvata, pa obično do 2 dana
nakon operacije plasirani su perikardijalni drenovi prednji, ispred desne komore i drugi stražnji, iza i ispod LV-a.
Ovi drenovi bili su razlogom nepostojanja razlike među veličinama postoperativnih perikardijalnih izljeva kod ispitivane i kontrolne skupine, u navedenim područjima dreniranja perikardijalnog prostora.
Skrenuli bi sada pažnju na prednosti upotrebe statina, njihov odnos sa
drugim lijekovima, te mali broj sporednih efekata u odnosu na druge lijekove
koji se upotrebljavaju u tretiranju posperikardiotomnih perikardijalnih izljeva tj. NSAR, diuretika, kortikosteroida i kolhicina.
Upotreba statina je u stalnom porastu. Osobito je u posljednje vrijeme izražena potreba uzimanja statina, kako za
reguliranje visine vrijednosti kolesterola
i triglicerida, tako i za pleiotropne efekte
statinske terapije koji nisu zanemarljivi.
Posebno je važna potreba statina u
grupi kardiovaskularnih pacijenata dijabetičara, čiji je broj u našem radu bio
gotovo podjednak u obje skupine pacijenata, tj. 7 pacijenata (18%) u kontrolnoj
skupini, u odnosu na 8 pacijenata (19%)
u ispitivanoj skupini.
Statini koji su predmet intresovanja
u ovoj studiji, zaslužuju pažnju u pogledu opravdanosti njihove upotrebe
kod ovakvih pacijenata. Njihovo hipolipemijsko dejstvo je već dokazano velikim studijama, a pleiotropni učinci,
kao npr. antinflamatorno dejstvo, imu-
nomodulatorno dejstvo, efekat na endotelnu funkciju, dejstvo na oksidativni
stres, antiprokoagulabilni efekat, antiaterogeno dejstvo i dr. još nisu u punom
obimu niti dokazani, a niti su našli punu
primjenu (5, 6, 7).
Pokazalo se da su se statini u našem
radu i prije operativnog zahvata uzimali kod gotovo 50% pacijenata, a podaci iz prakse govore o potrebi mnogo
veće upotrebe hipolipemika, osobito kod
skupine kardiovaskularnih pacijenata,
dijabetičara. Osobno mišljenje je da je
potrebno sačekati rezultate studija koje
analiziraju upotrebu velikih doza statina, npr. dejstvo atorvastatina u dozi od
80mg/24.h. Nedavno je završena studija
sa 40mg atorvastatina, koji je preoperativno uključen u terapiji zajedno sa beta
blokerima i amiodaronom kod pacijenata
koji su podvrgnuti kardiohirurškoj operaciji i u toj grupi pacijenata došlo je do
signifikantnog smanjenja pojave postoperativne atrijalne fibrilacije (8, 9).
Statini nemaju izrazitih sporednih
efekata, osim miopatije u <1% slučajeva.
Interakcije statina sa drugim lijekovima
su neznatne ili beznačajne, osobito kada
se radi o preparatima za liječenje kardiovaskularnih bolesti. Pošto se metaboliziraju preko CYP3A4 potreban je oprez
kod istovremenog uzimanja fibrata i
gemfibrozila, amiodarona, diltiazema
i drugih nedihidropiridinskih blokera
kalcijumskih kanala, nekih antidepresiva, inhibitora HIV proteaze (indavir,
mekfinavir, ritonavir, sanquinavir), nekih makrolidnih antibiotika (eritromicina), i ciklosporina.
6. ZAKLJUČCI
Naše istraživanje je pokazalo da u
ispitivanoj skupini kardiovaskularnih
pacijenata u odnosu na kontrolnu skupinu postoji:
• Ne postoji signifikantna razlika
u odnosu na demografske podatke kliničku sliku i laboratorijske parametre
među kontrolnom i ispitivanom skupinom,
• Postoji signifikantna razlika u prisustvu i održanju postperikardiotomnih
perikardijalnih izljeva u ispitivanoj u odnosu na kontrolnu skupinu, u projekcijama zidova ispred lijevog ventrikula i srčanog vrha, te oko lateralnog zida.
• Navedena razlika postoji na pomenutim područjima u svim postoperativnim periodima do 14 postoperativnog dana,
• Studija je obradila skupinu pacije-
MED ARH 2009; 63(3) • ORIGINALNI ČLANCI / ORIGINAL PAPERS
155
Uticaj statina na postoperativni tretman pacijenata operiranih radi ugradnje aortokoronarnih premoštenja
nata koja nije imala izrazito velikih postoperativnih perikardijalnih izljeva, pa
su mnogi medikamentozni efekti (a i oni
statina) smanjeni,
• Statini su pokazali dobar antiinflamatorni učinak na ovako ograničenom broju pacijenata,
• Statinska terapija je u našoj studiji
aplicirana bez sporednih efekata i bez interakcija sa drugim postoperativno upotrebljenim lijekovima,
• Statinska terapija bi se uz ostalu
terapiju, trebala obavezno nastavljati u
ranom kardiohirurškom postoperativnom periodu,
• Antiinf lamatorno dejstvo statina potrebno je i dalje ispitivati, i to na
mnogo većoj skupini pacijenata,
• O antiinflamatornom dejstvu hipolipemika nema do sada velikih studija
koje bi odagnale svaku sumnju u antiinflamatorno dejstvo hipolipemika,
• Posebno treba istaći da nema velikih studija koje bi istraživale antiinfla-
156
Lancet, 1999;353:118-9.
matorno dejstvo hipolipemika na pri6. Hernandez-Perera O, Perez-Sala D, et al.
mjeru postperikardiotomnih perikarEffects of the 3-hydroxy-3methylglutaryldijalnih izljeva.
LITERATURA
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3.
4.
5.
CoA reductase inhibitors, atorvastatin
and simvastatin, on expresion of endothelin 1 and endothelial nitric oxide synthase in vascular endothelial cells. J Clin
Invest, 1998; 101:2711-9.
Kaesemayer WH, Caldwer RB, Huang JZ
et al. Pravastatin sodium activates endothelial nitric oxide synthase independent
of its cholesterol-lowering actions. J Am
Coll Cardiol, 1999;33:234-41.
A. Selcuk Adabag et al. Statins May Reduce Atrial Fibrillation in Heart Failure
Patients Am Heart J, 2007;154:1140-114.
Lertsburapa K, White CM, Kluger J, Faheem O, Hammond J, Coleman CI1: Preoperative statins for the prevention of
atrial fibrillation after cardiothoracic
surgery. J Thorac Cardiovasc Surg, 2008
Feb;135(2):405-11.
Meurin P, Weber H, Renaud N, et al. Evolution of the postoperative pericardial
effusion after day 15*. The Problem of the
7.
late tamponade. Chest, 2004;125:2182-7.
Pepi M, Muratori M, Barbier B, et al: Pericardial effusion after cardiac surgery:
incidence, site, size, and hemodynamic
consequences. Br Heart J, 1994; 72:327.
Mulvagh SL, Rokey R, Vick 3rd GW, et al. 8.
Usefulness of nuclear magnetic resonance
imaging for evaluation of pericardial effusions, and comparison with two-dimen- 9.
sional echocardiography. Am J Cardiol,
1989; 64(16):1002-9.
Alkhulaifi AM, Speechly-Dick ME, Swanton RH, et al: The incidence of significant
pericardial effusion and tamponade following major aortic root surgery. J Cardiovasc Surg, 1996: 37:385.
Strandberg TE, Vanhanen H, Tikkanen
Kontakt adresa autora: dr. Mehmed Kulić.
MJ. Effect of statins on C reactive protein Institut za srce. KCU Sarajevo. Bolnička 25. Tel.:
00 387 33 297 000.
in patiens with coronary artery disease,
MED ARH 2009; 63(3) • ORIGINALNI ČLANCI / ORIGINAL PAPERS
Effectiveness of Diabetes Flow Sheet in Controlling Blood Pressure: Should Family Medicine Teams in Zenica Use Recommended Guidelines?
Effectiveness of Diabetes Flow
Sheet in Controlling Blood Pressure:
Should Family Medicine Teams
in Zenica Use Recommended
Guidelines?
Larisa Gavran1, Olivera Batic-Mujanovic2, Selmira Brkic3, Sabina Nuhbegovic4
Faculty of Health Sciences, University in Zenica, Bosnia and Herzegovina1
Faculty of Medicine, University in Tuzla, Bosnia and Herzegovina2,3,4
Original paper
SUMMARY
Background: Blood pressure (BP) is one of the important parameters for controlling Diabetes Mellitus (DM).
European Society of Cardiology recommended optimal level for DM BP≤130/80mmHg. Aim: We wanted to
assess the level of BP for our DM patients after using specific guidelines for DM. Methodology: Retrospective
medical record (audit) has been conducted among 853 DM patients older then 18 years. We checked patient
charts among 19 FM teams two years before (May 2003-May 2005) and two years after (May 2005-May 2007)
implementation of the DM guidelines in Family Medicine (FM) clinic in Zenica. We divided FM teams based on
their patients BP values; optimal level of BP≤130/80mmHg; suboptimal level when systolic BP 130-140mmHg
and diastolic 85 -90mmHg and that with inadequate level with BP>140/90mmHg. Results: 853 DM patient
charts were analysed, 46 per FM team. Average age of DM patients was greater than 60 years and average age
of doctors was 46.6. Percentage of BP inadequate level was smaller after implementation of DM guidelines in
most of FM teams. For optimal level BP≤130/80mmHg, significant improvement was seen after implementation of DM guidelines for: 6/19 teams (p<0. 0001), 2/19 teams (p<0.001) and 2/19 teams (p<0. 01). Conclusion: After implementation of BP guidelines for DM patients, BP can be improved in patients treated by FM
teams and guidelines should be used.
Keywords: blood pressure, diabetes mellitus, guidelines, family medicine teams
1. INTRODUCTION
Hypertension is common in patients
with type 2 diabetes with a prevalence of
40-60% over the age range 45 to 75 (1).
Raised blood pressure (BP) is more common in people with type 2 diabetes than
in the general population. However, in
patients with type 2 diabetes the risk of
diabetes complications was strongly associated with raised blood pressure (2)
Most recent guidelines for BP management end treatment recommended:
BP to be measured at every diabetes
clinic visit for the assessment of hypertension, optimalisation of BP level (target are <130/80mmHg) with using of
angiotensin converting enzyme (ACE)
or angiotensin receptor blocker (ARB)
for treatment of hypertensive patients
and using of antithrombocit therapy.
Also, lifestyle interventions to reduce BP
should be considered (3, 4, 5).
Several studies have show the efficancy of diseases-specific flow sheet use
for improving patient care (6,7). On the
other hand, there are only one studia in
primary care settings examinig how often flow sheets are used to guide diabetes care and effectiveness of diabetes
flow sheet use for improveing patients
outcomes (8). In this study we wanted
to assess the relationship between special diabetes flow sheets use and patients
level of blood pressures in the everyday
practice of primary care. This article is
one in series our articles about quality
improvement of care for diabetes type
2 patients cared by Family physicians in
Zenica municipality.
2. METHODS
In May of 2005 the Council management of Health Insurance Institution in
Zenica-Doboj Canton (ZDC) adopted a
resolution called “Primary conditions
needed for recognition of Family Medicine in ZDC”. One of these conditions included re-establishing a “system of active
management on diabetes and hypertension” (resolution number: 01-100-22/05:
page 4, 2005). One of these conditions
involved special flow sheets for patients
with diabetes and hypertension and
these are put in the patient’s paper chart.
The special flowsheet for diabetic
patients (SFD) includes 13 parameters
which are followed periodically. One
of these parametar is a blood pressure
witch is need to be measured every 6
months. For every hypertensive patients
ACE or ARB need to be given.
A retrospective medical record (audit) was conducted in Home of Health in
Zenica in 20 Family Medicine Clinic to
describe the level of BP of diabetic care
in the two years before (May 2003-May
2005) and two years after (May 2005May 2007) implementation guidelines
for DM.
Data was analysed for 843 patients.
Nineteen FMT ( Family Medicine Physician is the Team leader) in Zenica participated in this study and allowed us to
look into the medical charts of their diabetic type 2 patients. For every FMT
, the diabetic patients were chosen using the following criteria: age 18 year
or older, diagnosed as DM type 2 by International Qualification of Diseases -9
revision (E11, E10 or DM type 2 ), presenting in the Family Medicine Clinic at
least one time before and one time after
the implementation of SFD, followed by
Family Medicine Physician without specialist-/endocrinologist consultation.
By random sampling patients’ charts
which met those criteria were reviewed.
Charts which did not satisfy those criteria were excluded and others picked.
Data from charts was documented on a
special audit form (DM flow sheet), created from SFD. We divide all founded
BP and all FM teams on that who get a
optimal level of BP≤130/80 mmHg; sistolic 130-140 mmHg and diastolic 85 -90
mmHg as suboptimal level and that with
inadequate level BP>140/90mmHg (4).
In Home of Healt in Zenica municipality did not egzist appropriate institutional review board yet. Director of our
institution and colegues Family Medicine physicians approved the project.
The data was analysed by standard
methods of descriptive and inherent
statistics. The hypotheses were tested
by z- test proportion. Statistically significant difference was defined as a P
value of <0.05.
3. RESULTS
In total 853 SFD were reviewed. In
patient’s sample, women were more
than men (538; 63.1% vs. 315; 36.9%)
(P<0.0001). The average age was greater
than 60 years (603; 70.7%). Nineteen
FMT in total had 44008 registered patients and 1578 patients with DM. On
average every FMT had 2316 patients
and 83 diabetic patients: the study analysed 45 SFD per team. Within the FMT,
Family medicine specialists comprised
MED ARH 2009; 63(3) • ORIGINALNI ČLANCI / ORIGINAL PAPERS
157
Effectiveness of Diabetes Flow Sheet in Controlling Blood Pressure: Should Family Medicine Teams in Zenica Use Recommended Guidelines?
Blood presure
Blood pressure
(>140/90 mmHg)
inadequate level
Blood pressure
(130-140)/(85-90 mmHg)
suboptimal level
Blood presure
(≤ 130/85 mmHg)
optimal level
Number of patients
(N=853)
Before
SFD
Proportions of patients
After
SFD
Before
SFD
After
SFD
500
298
(P<0.0001)
58%
34%
43
286
(P<0.0001)
5.04%
33.5%
95
219
(P<0.0001)
11.1%
25.6%
Table 1. Before and after implementation Special Flow sheets for diabetes (SFD) and proportion of
patients who met blood presure level for Family Medicine Teams together
74%, doctors with Program of Additional
Training (PAT) comprised 21% and Family medicine residents were 5%. The average physician age was 46.6 years: 21%
were men and 79% were female.
Table 1 show number and proportion of diabetes type 2 patients for: blood
pressure (>140/90 mmHg) as a inadequate level statisticly significant decrease after SFD (298 vs. 500; P<0.0001 ;
blood pressure (130-140)/(85-90 mmHg)
as a suboptimal level statisticly significant increase after SFD (286 vs. 43;
P<0.0001) and blood presure (≤ 130/85
mmHg) as a optimal level statisticly significant increase after SFD (219 vs.95;
P<0.0001) for all Family Medicine Teams tougether. Finaly, 25.6% of diabetic
typ2 patients had optimal level of blood
pressure(≤ 130/85 mmHg) and 59.1% of
diabetic typ2 patients had BP <140/90
mmHg.
Table 2 show number of diabetes
type 2 patients with inadequate (>140/90
mmHg), suboptimal (130-140)/(85-90)
and optimal(≤ 130/85 mmHg) blood
pressures level per Family medicine
Teams before vs. after implementation
of flow sheets for DM.
For optimal level frequency of those
findings were rare before SFD. Statistical significance difference was found per
FMT: 2, 11, 12, 13, 14 and 18 (P<0.0001),
for FMT 15, 17 level of significance
(P<0.01), and FMT 5 and 6 (P<0.01).
4. DISCUSSION
assess the association’s betwen the use of
Specific Flow sheet for diabetes and adherence to care guidelines for diabetes
in everyday practice of primary care (8).
From 853 charts before vs.after implementation of SFD, the best regularity
in registration were found in parametar
BP (30.2% vs. 81.3%) and “given ACE ili
ARB“ (57% vs.75.7%) per FMT tougether.
With that FMT in Zenica reach one of
criteria in “Guide for Accreditation for
ambulantas/FMT in Republica Srpska”
done by Agency of Accreditation and improvement of Quality Health Care in Republica Srpska : FMTs must ensure that:
80% of patients must have blood pressure
documented on every visit (13). Also, in
two studies Harris SB at all. (1998 and
2003) examined level of folowing guideBlood presure (BP)
Family
Medicine
Team
Number of
checked
chart
lines for DM in family practice and also
found that BP is mensuared in 88% of
cases (14,15).
Agency for Healthcare Research and
Quality in United States of America
made National Healthcare Quality report in 2005 were only 70.9% all of diabetic patients had controled BP <140/90
mm/Hg (16). Our study show that only
25.6% of diabetic typ 2 patients had optimal level of blood pressure(≤ 130/85
mmHg) and only 59.1% of diabetic typ2
patients had BP <140/90 mmHg.With
those findings we can not be satisfied.
In addition, studies which include doctors’ reports, audits of practice and review of administrative data show that
the quality of DM control practiced by
doctors in Primary Health Care (PHC)
is suboptimal (9, 15, 17, 18). On the other
hand, our study show that optimal level
BP per FMT before vs. after implementation of SFD statistically significant
improved for FMT: 2, 11, 12, 13, 14 and
18 (P<0.0001), for FMT 15, 17 level of
significance (P<0.01), and FMT 5 and
6 (P<0.01).
So many studies explore most useful
interventions for improving a diabetes
care (19, 20, 21, 22, 23, and 24). Some of
those suggesting that: changing clinician
behavior, changing the practice organisation, enhancing information systems
can improve disease management (19),
Blood presure
(>140/90
mmHg)
Inadequate level
Blood presure
(130-140)/(85-90)
suboptimal level
Blood presure
(≤ 130/85 mmHg)
optimal level
Before
SFD
Before
SFD
Before
SFD
After
SFD
After
SFD
After
SFD
Z-tests
for
optimal
level
(BP)
P-Value
for
optimal
level
(BP)
1
41
29
4
12
20
0
17
-
-
2
49
29
17
18
16
2
16
3,5
<0.0001
3
50
20
21
20
17
10
12
0,5
0.63
4
41
26
16
13
13
2
12
2,9
0.03
5
40
25
19
12
4
3
17
3,0
<0.01
6
46
31
25
12
2
3
19
3,2
<0.01
7
46
33
24
13
8
0
14
-
-
8
40
17
20
20
14
3
6
1,1
0.3
9
44
26
21
18
13
0
10
-
-
10
41
27
10
14
11
0
20
-
-
11
40
25
11
14
12
1
17
4,3
<0.001
12
48
28
15
18
12
2
21
4,4
<0.001
13
50
35
10
14
6
1
34
6,6
<0.001
Many studies estimate the risk and
14
46
26
11
18
16
2
19
3,9
<0.001
concequestions of complications in dia15
49
28
15
19
14
2
20
3,5
<0.001
betic patients (9-12) were any reduction
16
46
17
17
23
15
6
14
1,1
0,27
in blood pressure is likely to reduce the
17
47
22
12
21
13
8
18
2,6
<0.01
risk of complications with the lowest risk
18
43
29
15
12
10
2
18
3,7
<0.001
being in those with systolic blood pres19
46
37
18
9
15
0
13
sure less than 120 mm Hg (2). On the
Table 2. Blood presure level before vs. after implementation Special Flow sheets for diabetes typ 2
other hand, this is one of rare study to patients (SFD) per Family Medicine Teams-FMT
158
MED ARH 2009; 63(3) • ORIGINALNI ČLANCI / ORIGINAL PAPERS
Effectiveness of Diabetes Flow Sheet in Controlling Blood Pressure: Should Family Medicine Teams in Zenica Use Recommended Guidelines?
Diabetes, 2003; 27(Suppl 2): S1-152. www.
cian, 2003; 49:778-85.
and on the other hand quarterly site visdiabetes.ca/cpg 2003.
16. Agency for Healthcare Research and Quits and yearly meetings for Primary care
4. European guide for Prevention of Cardiality. National Healthcare Quality report
clinics can improve patient follow up and
ovascular duseases in Clinical practice
2005, http://www.ahrq.gov/qual/nhdr05/
treatment as well as improve adherence
u. European Heart Journal, 2003; 24 (17):
nhdr05.htm
to clinical practice guidelines for blood
1601-10, and European Journal of Cardi- 17. Kirkman MS, Williams SR, Caffrey HH,
ovascular Prevention and Rehabilitation,
David GM. Impact of a program to Impressure (24).
2003;10(4):S1-S11.
prove Adherence to Diabetes Guidelines
Our method of creathing guidelines
5. American Diabetes Association: Standard
by Primary Care Physicians. Diabetes
adherence is innovative one especially
of medical care in diabetes Diabetes Care,
Care, 2002;25:1946-51.
in Bosnia and Hercegovina for Primary
2009;32(suppl 1.):S115-S117.
18. Gill JM, Di Prinzio MJ. The Medical SociHealth Care and it is creating to help 6. Ruoff G.A mehod that dramaticaly improety of Delaware’s Uniform Clinical GuiFamily Physician to give better care for
ves patient adherence to depression treadelines for diabetes: did they have a potment. J Fam Pract, 2005;54(10):846-52.
sitive impact on quality of diabetes care?
they patients in every day practice.
7.
5. CONCLUSION
Study show that after implementation of Special diabetes flowsheet in
Family Medicine settings in Zenica,
Family Medicine Teams improved documentation and most of them rich optimal level of BP. Also, study show that
use of Special diabetes flowsheet is associated with increased adherence to
guidelines for diabetes care and may be
a valuable tool in improveing care.
Finally, new research is needed to
investigate the reasons why all Family Medicine Teams in Zenica do not
achieve the recommended guidelines
for blood pressure controll in diabetes
typ 2 patients .
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Corresponding author: Larisa Gavran, MD,
Family medicine specialist, ECFM Travnicka,
Faculty of Health, University in Zenica Bosnia and
Herzegovina E-mail:gavranlarisa@yahoo.com
MED ARH 2009; 63(3) • ORIGINALNI ČLANCI / ORIGINAL PAPERS
159
Collective Immunity of the Population from Endemic Zones of Hemorrhagic Fever with Renal Syndrome in Kosovo
Collective Immunity of the
Population from Endemic Zones
of Hemorrhagic Fever with Renal
Syndrome in Kosovo
Sefedin Muçaj1.,3, Serbeze Kabashi 3, Salih Ahmeti 2.,3, Isuf Dedushaj1.,3, Naser Ramadani1.,3, Tatjana Avsic-Zupanc4
National Institute of Public Health of Kosovo, Pristine, Kosovo1
Infectious Disease Clinic, University Clinical Centre of Kosovo, Kosovo2
Faculty of Medicine, Pristine University, Kosovo3
Department of Microbiology, Faculty of Medicine, Ljubljana, Slovenia4
Original paper
SUMMARY
Hemorrhagic fever with renal syndrome (HFRS), also known as mice fever is an acute viral zoonosis and it
appears in the natural focus after the human contact with Hantaan virus infected mice. The objective (purpose) of this study was to investigate the prevalence of specific antibodies in HFRS, in convalescent persons
(collective immunity in endemic hearths).In this project we applied the epidemiological method of studying
with retrospective-perspective, the serological method for determination and detecting antibodies from the
persons of epidemical focus and statistical methods. The disease diagnosis is based on the epidemiological,
clinical and serological records. The collected samples have been sent to referral laboratory in Medical FacultyInstitute of Microbiology Ljubljana for laboratory confirmation. From the results we came to conclusion that
in the territory of Republic of Kosovo, the HFRS is still a serious health, economic and biological problem. The
lethality rate from HFRS in 1986 was 15.4%, 1986-89 10.8%, from 1995-2006 8.70%. The lowest rates of morbidity, mortality and lethality of HFRS compared with the previous periods of time, prove collective immunity
growth in Dukagjini valley. For collective immunity research and to conduct the persistence of antibodies for
viral corresponding (relative) antigen, after the disease, the samples were collected in the time period of MayJune 2008, with 203 persons that were tested with serological method IIF (Indirect immune fluorescence) from
which 187 cases (92.1%) resulted sero-negative and 16 cases (7.9%) resulted sero-positive with HFRS. This
proves the collective immunity increase for HFRS. From 13 recovered patients previously diagnosed with HFRS
(1986-1989-1995), levels of antibodies were screened in 2008 with IIF. Out of 13 persons, positive antibodies
were found in 10 cases, while 3 cases were negative for antibodies (HTN, PUU, and DOB).After 13, 19 and 22
years HTN, PUU and DOB antibodies persisted in level (1:16-1:512). Based on the gathered results, we came to
conclusion that it is necessary to compile the National Strategy of Surveillance for the Kosovo Health System
for a 5 year period, for avoiding this high risk disease.
Keywords: HFRS, collective immunity, (HTN, PUU, DOB) antibodies persisted after 13, 19 and 22 years, IIF,
Republic of Kosovo
1. INTRODUCTION
Haemorrhagic Fever with Renal Syndrome (HFRS), or else known as ‘mice fever’, is an acute viral zoonosis, that appears in natural hearths after the humans get in contact with some sorts of
mice infected with the Hantaan virus
(ARN virus). This disease has a wide
geographical spread, and it is present
in almost all European countries, especially in Balkans, and Kosovo is not excluded from attacks. There are diseases
and natural hearths of two sorts of viral
haemorrhagic fever in Kosovo: haemorrhagic fever with renal syndrome (HFRS)
and Crimean Congo Haemorrhagic Fever (CCHF).Natural hearths of HFRS in
Kosovo are: Bjeshkët e Nemuna, Mountains of Peja, Deçan, Junik, Gjakova, Istog and Kashtanjeva in Ferizaj.The scale
of resistance of a population towards a
particular communicable disease is determined with collective immunity.With
the increase of the collective immunity,
comes also the decrease of the scale of
morbidity, mortality and lethality from
160
the particular diseases (HFRS) and vice
versa. Sensitivity towards HFRS is general. All those who are in contact with
the disease virus become ill, but most
vulnerable are: farmers, mountain trackers, campers, shepherds, mountain rangers and collectors of natural fruits. After the recovery from the disease, comes
the decrease of the antibodies, which
shows the possible existence of re-infection with other types of Hantaan viruses. Various authors have found traces
of specific antibodies against the Hantaan virus, even 34 years after the disease
(1,2,3,4). Other researches show that in
natural hearths, seropositivity in Hantaan is 2-29%, while in Europe it’s in 2.1%
of population (5,6,7,8,9).
2. AIMS, methodology,
and materials
To investigate the persistence of specific antibodies in HFRS, in convalescent persons (collective immunity in endemic hearths).
Epidemiological method of study was
MED ARH 2009; 63(3) • ORIGINALNI ČLANCI / ORIGINAL PAPERS
used, retrospective-perspective component, serologic method and statistical
method. Diagnosis of the disease was
done based on the epidemiological, clinical and serological data. For verification
of the HFRS disease cases, laboratory
research – serological testing was done,
with the following methods: IIF (Indirect
immune fluorescence) and the modern
method of PCR (polymerase chain reaction) for acute cases. The collected samples (serums) were sent to the referent
laboratory in the Faculty of Medicine
– Institute of Microbiology- Ljubljana,
for their laboratory confirmation.The research on the collective immunity scale
on HFRS was achieved with: Serological Tests–detection of antibodies (Ab)
in serum and epidemiological research,
we have used the continuous epidemiological surveillance in the field, case
research, data collection on the movement of the disease, health indicators,
like: scale of morbidity, mortality and lethality. Results’ testing was done with Ttest, Spearman’s correlation and X2-test.
Test verification was done for credibility
95% and 99%.
2. RESULTS
For researching the collective immunity and follow up on antibodies persistence for respective viral Ag
(HTN, PUU, DOB), during the period
May-June 2008, the following was done:
blood samples(serums) were taken from
203 persons and after the testing made
with serological method IIF, the following results came out: 187 serums or
92.1% were negative on HFRS and 16 serums or 7.9% were positive on HFRS, as
well as the follow up of health indicators like: morbidity, mortality and lethality scale for HFRS during the period
1995-2006. This was proved even during our research, 1995-2006 in Kosovo,
where a low scale of morbidity, mortality and lethality of HFRS was registered,
compared to other earlier time periods,
which results in high scale of collective
immunity on HFRS in Kosovo during
the time of our research (Table 1 and 2).
During May-June 2008, with the serological method IIF, research of 203
samples (serums) was done, where 187
serums or 92.1% were negative on HFRS
and 16 serums or 7.9% were positive on
HFRS. This proves the increase of the
collective immunity scale of the population of endemic zones characteristic
with HFRS (Table 3).
Collective Immunity of the Population from Endemic Zones of Hemorrhagic Fever with Renal Syndrome in Kosovo
Time Period
1996-2006
Lethality and Balkans. Similar Le- (8.70%). This is explained due to the fact
(%) thality was not registered that after the 1986 epidemics, sufficient
8.70 anywhere else in Europe, experience was gained, not only in cur-
Mb/100.000 Mt/100.000
0.16
0.02
with exception of Bul- ing, but also in diagnosing, which exgaria and Albania, and plains why the lethality has decreased
in the Far East (1,4,10). from 15.3% (1986) to 8.7% (1995-2006).
This is explained with This means that the increasing scale of
Time Period
Lethality (%)
the heavy forms of the resistance of population or the collective
1986
15.40%
illness as well as with the immunity on HFRS , results with the de1986-1989
10.80% lack of sufficient experi- crease of these health parameters, re1995-2006
8.70% ence in curing of these ill- spectively, decrease of Mb, Mt and Le.
Table 2. Movement of Lethality scale (%) of HFRS in Kosovo, during nesses, in the first year of According to the foreign literature, the
different time periods
epidemics.Lethality scale lethality scale of HFRS varies: in Soof HFRS during various viet Union Le- 3-22%, then decreases
Out of 13 convalescents (that have
time periods marks a decrease as follows: to 10-15%, Korea Le – 5-20%; Greece
undergone the acute disease during
in 1986 it was 15.4%, afterwards during Le – 13%; Albania Le – 28.1%; Scandi1986, 1989, and 1995), we have determined the level of antibodies for the viHFRS – IIF
Total
Tested
ral Ag (HTN, PUU, DOB), in 2008, with
Seronegative
% seropositive
%
N
%
the indirect immune fluorescent method
Contact 1*
43
23.0
12
75.0
55 27.1
(IIF). Out of all these convalescents, perContact 2**
79
42.2
3
18.8
82 40.4
sistence of antibodies was found in 10
Haemodialysis
persons, while in 3 others we did not find
29
15.5
1
6.3
30 14.8
Pat.
antibodies persistence for respective viHealth Personnel
16
8.6
0
0.0
16
7.9
ral Ag. In 4 convalescents (ex acute paControl Group
20
10.7
0
0.0
20
9.9
tients in 1986), testing with indirect imN
187
100.0
16
100.0
203 100.0
mune fluorescent method (IIF) was done
Total
%
92.1
7.9
100.0
in 2008(after 22 years); in two of them
were found levels of antibodies for vi- *Contact 1 or the first family circle – means close family members that live with the patient
ral Ag HTN, PUU, DOB (from 1:32 to with HFRS ** Contact 2 or the second family circle – means members of the family that live
1:256), while in the other two, levels of together in the endemic zones characteristic with HFRS
antibodies for respective viral Ag were
Table 3. Detection of immune fluorescent Antibodies in population living in the natural
not found (Table 4).
hearths characteristically with HFRS, 2008, Kosovo
Also, in 4 other convalescents (ex
acute patients in 1989), testing was
1986-1989, it was 10.8%, in a way that it navia and Western Europe Le – 0.5-1%
done with indirect immune fluorescent
continuously decreases; even also dur- (1,4,10). This shows that the Lethality
method (IIF), in 2008 (after 19 years),
ing the period 1995-2006 it was lower scale in Kosovo is much lower compared
and in 3 of them, levels of antibodies of
viral Ag HTN, PUU, DOB were found
(Convalescents)
(from 1:16 to 1.512), while in one case,
Antibodies level of HFRS 2008
Time
Nr. ex patients with
Municipality
Contact
period
levels of antibodies for respective viral
HFRS
HTN
PUU
DOB
Ag were not found. In 5 convalescents
1
1986
Deçan
first
1:256
1:64
1:256
(ex acute patients in 1995) testing was
19862
1986
Pejë
first
1:32
neg
1:64
done with indirect immune fluorescent
2008 (22
3
1986
Pejë
first
neg
neg
neg
method (IIF), in 2008 (after 13 years),
years)
4
1986
Pejë
first
neg
neg
neg
and in all of them, levels of antibodies
of viral Ag HTN, PUU, DOB were found
5
1989
Pejë
first
1:128
1:16
1:256
1989(from 1:16 to 1.256) (Table 4).
6
1989
Gjakovë
first
1:512
1:32
1:512
2008 (19
At the patients, in which the acute
7
1989
Pejë
first
1:32
1:16
1:64
years)
disease (HFRS) has passed before 13, 19,
8
1989
Deçan
first
neg
neg
neg
and 22 years, we did not gain any signif9
1995
Deçan
first
1:256
1:32
1:128
icant difference in the levels of antibod10
1995
Pejë
first
1:32
neg
1:64
1995ies for viral Ag: for HTN (r = 0.3000,
11
1995
Klinë
first
1:64
1:32
1:128 2008 (13
p>0.05); for PUU (r = 0.16, p>0.05), and
years)
12
1995
Istog
first
1:32
neg
1:64
DOB (r = 0.21, p>0.05). (Table 4)..
Table 1. Movement of average morbidity, mortality and lethality
scale of HFRS, Kosovo, 1995-2006
13
3. DISCUSSION
1995
Gjakovë
first
1:128
1:16
r
r =-0.300
=-0.16
Spearman’s correlation
p>0.05
p>0.05
1:64
r =-0.21
Lethality scale of HFRS was higher
p>0.05
in Kosovo in 1986, with 15.4%, compared to other neighbouring countries Table 5. Table presentation showing persistence levels of antibodies of viral Ag (HTN, PUU, DOB),
(average Lethality in ex YU was 5.2%) during various time periods, 13, 19 and 22 years after the disease.
MED ARH 2009; 63(3) • ORIGINALNI ČLANCI / ORIGINAL PAPERS
-
161
HTN
PUU
DOB
13 years
19 years
22 years
Collective Immunity of the Population from Endemic Zones of Hemorrhagic Fever with Renal Syndrome in Kosovo
World of Microbes EDK, Paris, France,
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Figure 1. Photos with indications from Haemorrhagic Fever (HFRS), hospitalized in the
complete genome sequence of a CrimeanFigure
1.
Photos
with
indications
from
Haemorrhagic
Fever
(HFRS),
hospitalized
in
the
Infectious Disease Clinic in Pristina (Inf. Clinic – Prof. Dr. Salih Ahmeti)
Congo hemorrhagic fever virus isolated
Infectious Disease Clinic in Pristina (Inf. Clinic – Prof. Dr. Salih Ahmeti)
from an endemic region in Kosovo. Vito other countries. During our research, Disease Clinic and other personnel of
rol J. Jan, 2008; 15;5:7. PMID:18197964
[PubMed-indexed for MEDLINE].
May-June 2008, we have collected blood UCCK, regional hospitals and primary
5. DISCUSSIONS
samples (serums) from 203 persons and health care; but it was missing at it is 4. Duh D, Saksida A, Petrovec M, Dedushaj
Lethality
scale of
HFRS
was higher
inIIF,
Kosovo
1986, the
withauthentic
15.4%, compared
to other I, Avsic-Zupanc T. Novel one-step realstill in
missing
governmenafter testing
with
serologic
method
neighbouring
countries
(average
Lethality
in
ex
YU
was
5.2%)
and
Balkans.
Similar time RT-PCR assay for rapid and specific
we had the following results: out of 203 tal programme, which would prevent any
diagnosis of Crimean-Congo hemorrhagic
Lethality
was
not registered
anywhere
else future
in Europe,
with exception
of Bulgaria
samples
(serums)
tested, 187
serums or
appearance
and new deaths
from and fever encountered in the Balkans. J Virol
(1, 4 ,10)
.
This16is explained
with
the heavy
forms of the illness Methods. 2006 May;133(2):175-9. Epub
Albania,
in negative
the Far East.
92.1% and
were
on HFRS and
this disease
(1,4,10)
Dec 15.PMID: 16343650 [PubMed–inserums or 7.9% were positive on HFRS.
dexed for MEDLINE], 2005.
This means that specific HTN antibod- 4. CONCLUSIONS
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data from foreign literature, specific an- was lower, 8.70%; Low Morbidity, MorA.Monitoring rodent fluctuations, rodenttibodies on HNT were found in 1.9-29.1% tality and Lethality scale form HFRS
borne viruses and hanta epidemiology
of population from the natural hearths of compared to earlier time periods, results
in Finland. In: VI th International Conference on hemorrhagic fever with renal
this disease - in Europe, in 2.1% of popu- with increase of the collective immunity
syndrome, hantavirus pulmonary synlation. Out of all these convalescents, the in the population from natural hearths
drome and hantaviruses, 23-25 de junio,
persistence of Antibodies was found in of HFRS; During May-June 2008, with
Seúl. The National Academy of Sciences,
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Mortality and Lethality scale. All this 1. Avsic-Zupanc T, Petrovec M, Duh D, Dedushaj I, Ahmeti S. Description of nosocowas achieved thanks to the hard work
mial and inrafamiliar spread of CCHF in
of the experts from NIPHK and regional
Kosovo during the 2001 epidemic. In: The
IPH’s, health personnel of the Infectious
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MED ARH 2009; 63(3) • ORIGINALNI ČLANCI / ORIGINAL PAPERS
Corresponding author: Ass. Dr. Sefedin
Muçaj, MD, PHD, Department of Epidemiology,
National Institute of Public Health of Kosovo,
Pristine (sefa66@gmail.com; mob tel. +377 44
223 782
Liječenje Hallux valgusa osteotomijom prve kosti metatarzusa po Krameru
Liječenje Hallux valgusa
osteotomijom prve kosti
metatarzusa po Krameru
The Kramer Osteotomy in the Treatment of Hallux Valgus
Sahib Muminagić, Sanja Drljević, Amela Granić, Tarik Kapidžić, Mehmed Kovačević, Faruk Hodžić
Ortopedsko odjeljenje bolnice Crkvice, Kantonalna bolnica Zenica, Bosna i Hercegovina
Stručni članak
SAŽETAK
Vlastitu tehniku u liječenju hallux valgusa J. Kramer publicirao je 1973. godine (Orthopädische Pra Xis Heft
8/1982, 636-645). Lošu poziciju prve kosti metatarzusa sa svim posljedicama koja leži u osnovi deformiteta
ispravlja osteotomijom prve kosti metatarzusa i ponovo uspostavlja funkcionalnu ravnotežu prve grane stopala
u svim komponentama. Nakon iskustva, poslije 550 operiranih pacijenata, autor smatra da je ova metoda u
prednosti nad mnogim prije opisanim metodama, indikaciono je područje praktično veliko, pri poštovanju
tehnike izvodi se jednostavno, post operativno liječenje ne zahtjeva imobilizaciju, a u poređenju sa drugim
metodama komplikacije i loši rezultati praktično su nepoznati. U periodu od 1984. do 1988. godine na našem
smo odjeljenju kod 98 oboljelog primijenili Kramerovu osteotomiju u liječenju hallux valgusa. Postigli smo
dobre rezultate, znatno bolje nego drugim metodama.
Ključne riječi: hallux valgus , Kramerova osteotomija, vlastiti rezultati
Professional paper
SUMMARY
In 1973. J.Kramer published his own technique for the cure of hallux valgus (Orthopädische Praxis Heft
8/1982, 636-645). He corrects bad position of the first bone of the metatarsus with all the consequences
which lie in the basis of the deformation. By osteotomy of the first bone of the metatarsus and re-instates
functional equipise of the first foot instep in all the components. Having the experience of 550 operated
patients he considered that this method has advantages over numerous described method, indicative range is
practically wide, respecting the technique it is simply performed, post-operative cure does not require immobilisation, and in comparison with other methods, complications and bad results are practically unknown. On
our ward, in the period between 1984 and 1988, we applied Kramer’s osteotomy in 98 cases of hallux valgus.
The results were satisfying, considerably better than after other methods of hallux valgus treatment.
Keywords: hallux valgus, the Kramer osteotomy, results
1. UVOD
zahvatom postigao dobar funkcionalni
i estetski rezultat, operator mora analizirati sve komponente deformiteta,
prošireno stopalo, lošu poziciju palca,
promijenjenu poziciju hvatišta tetive i
sezamoidnih kostiju, pseudoegzostozu
i degenerativne promjene u osnovnom
zglobu palca u smislu artroze. Operacije
na mehkim tkivima (tenotomije, transpozicija tetiva, kapsulloresekcije itd.),
ne samo da ne otklanjaju, nego dovode
i do novih patoloških opterećenja u predjelu palca i prednjeg stopala.
Resekcione metode na glavici metatarzalne kosti i bazi osnovnog članka
vode neestetskom stopalu, uz dalje opterećenje metatarzalnih glavica i mekih
tkiva. Stoga Kramer predlaže klinastu
resekciju prve metatarzalne kosti, sa izdašnom translacijom, čime utiče na sve
komponente deformiteta. Zahvat ima
široko indikaciono područje, tehnički
se jednostavno izvodi, hospitalizacija je
kratka, a u postoperativnom toku nije
potrebna gipsana imobilizacija.
Ovaj zahvat J. Kramer primjenjuje od
1973. godine i nakon iskustva u više od
550 operacija svoja zapažanja publicira
ra 1982. godine u „ Ortopädische Praxis“.
Ukoliko se napravi dobar preoperativni
plan i izbjegne greška u kirurškom izvođenju operacija, konačni rezultat uvijek
je odličan. J. Kramer navodi samo u 2
slučaja infekt kao komplikaciju.
1.1. INDIKACIJA
Ovom metodom može se korigirati
praktično svaki stepen hallux valgusa,
artroza osnovnog zgloba nije kontraindikacija, uvjet je jedino pokretljivost u
osnovnom zglobu palca (dorzalna fleksija ne smije biti manja od 40 stepeni).
goršati deformaciju. Vrlo rijetko sreOdmaknuti plac – čuklaj, statička
ćemo se sa kongenitalnim upalnim ili
je subluksacija prvog metatarzofalanposttraumatskim halusom valgusom.
geanskog zgloba, s lateralnom devijaciPoprečno proširen i spušten svod
jom velikog prsta od uzdužne osovine
stopala zajedno sa jednim od najčešćih
prve metatarzusne kosti više od 20° i
deformiteta, hallux valgusom, javlja se
medijalnom devijacijom prve metatarkao ortopedski problem, praktično u
zusne kosti. Prvi ga je opisao La Forest,
svakoj životnoj dobi. Da bi kirurškim
kirurg Louisa XVI (Luja 16.). Lelievre je
predložio termin – „angulacija prve zrake“, kako bi
se naznačilo da se radi o
složenoj leziji. Haluks valgus je deformacija u žena,
ali susreće se i u muškaraca
i djece. Uzrok nastanka je
multifaktorski, najčešće
kombiniran djelovanjem
unutarnjih (anatomske varijacija u strukturi stopala,
posebno juvenilnog) i vanjskih uzroka (nošenje nepogodne obuće). Stečena
deformacija sa spuštenim
metatarzusnim lukom stopala ne može se objasniti
nošenjem nepogodnih cipela, ali obuća može po- Slika 1 a i b. Tehnika: Paraosealno postavljanje Kiršnerove igle, supkapialna osteotomija, odstranjenje klina.
MED ARH 2009; 63(3) • STRUČNI ČLANCI / PROFESSIONAL PAPERS
163
Liječenje Hallux valgusa osteotomijom prve kosti metatarzusa po Krameru
Osnovno je da se osteotomijom ne dira
osnovni zglob palca koji će kasnije, nakon korekcije, preuzeti opterećenje. S
obzirom na to da osteotomija ne zahvata područje epifizne linije, Kramerova osteotomija, kao metoda ostaje kao
metoda izbora i u slučajevima juvenilnog hallux valgusa. Kratka hospitalizacija, postoperativno liječenje bez gipsa
i rano opterećenje bez potrebe za štakama čini operaciju prikladnom i kod
starih osoba.
2. materijal i metode rada
2.1. TEHNIKA
Preoperativni plan: predhodno je
potrebno napraviti rendgenski snimak
stopala u stojećem stavu pod opterećenjem u dorzoplantarnom smjeru i profilu. Napravi se skica na paus-papiru i
unese plan osteotomije, odgovarajućeg
ugla i klina sa medijalne strane prve
metatarzalne kosti. Zahvat se izvodi u
Slika 2. Elastični zavoj stopala sa blagim
pritiskom svih prstiju prema korigiranom palcu
nakon operacije odstrani se Kiršnerova igla.
tournique-u i općoj anesteziji, izuzetno
u regionalnoj blokadi stopala, dorzomedijalni rez u visini glavice prve kosti
međunožja stopala, subperiostalni pristup na dijafizu i aplikaciju Kiršnerove
igle (2 mm) paraosealno u palac. Ovo
je obavezno učiniti prije osteotomije.
Poprečna se osteotomija izvodi iznad
glavice, u druga, kosa u smjeru proksimalno-medijalno kao distalno-lateralno. Nakon odstranjenja odgovarajućeg klina (preoperativno planiranje,
skica), slijedi lateralizacija distalnog
fragmenta i ujedno plantaran dislokacija za 1-3 mm. Kiršnerova igla sada se
164
Slika 1 c i d. Tehnika: maksimalna lateralizacija, plantarni pomak 1-3 mm distalnog fragmenta,
postavljanje Kiršnerove igle u proksimalni fragment
fiksira u proksimalni fragment. Rezultirajuća sila nakon osteotomije (mišići
i postranični pritisak Kiršnerove igle)
djeluje okomito na kontaktne plohe. Lateralizacijom se pritisak još povećava i
prva se grana produžava.
Rezultirajuća sila nakon osteotomije (mišići i postranični pritisak Kiršnerove igle) djeluje okomito na kontaktne plohe. Lateralizacijom se pritisak
još povećava i prva se grana produžava.
Lateralizacija je obično maksimalna, najmanji za ½ širine metatarzusa na kosti. Lateralizacijom i plantarnim pomakom dolazi do repozicije sezamoidnih kostiju, a MTP zglob preuzima funkciju. Potrebno je paziti na pravilnu poziciju palca, izbjeći bilo kakav
pomak dorzalno ili plantarno u smislu
savijanja. Postoperativni tretman: mobilizacija prvog postoperatinog dana sa
opterećenjem i osloncem na petu. Nakon 14 dana odstrane se konci i ponovo
stavi elastična poveska.
Radna nesposobnost prosječno traje
od 8 do 10 sedmica, a ako se radi o pa-
Slika 3 i 4. Rendgenski snimak stopala preoperativno
MED ARH 2009; 63(3) • STRUČNI ČLANCI / PROFESSIONAL PAPERS
cijentu koji svoj posao obavlja sjedeći,
on se upućuje na rad sedmicu dana nakon odstranjenja Kiršnerove igle. U slučaju pojave otoka, provodi se manuelna
masaža, rijetko ultrazvuk i terapija Nemetrodinom.
Sličan kirurški zahvat može se izvesti kod digitus varus quintus, samo se
ne uzima klin, a učine se jedino steotomija i medijalizacija fragmenta.
Moguće greške: Osteotomija može
biti izvedena previsoko, pa postoji opasnost od pomaka u sagitalnoj osi i mogućnosti su korekture manje. Ako je
osteotomija izvedena prenisko, postoji
opasnost od nekroze glavice.
3. NAŠI SLUČAJEVI I REZULTATI
U periodu od 1984. do 2008. godine
primjetili smo Kramerovu metodu kod
98 pacijenata, kod 73 pacijenta operacija
je učinjena na oba stopala. Postoperativnih komplikacija nije bilo, a također
ni infekta. Kod 17 pacijenata zbog lahkog otoka i bolnosti koji je perzistirao
i nakon odstranjenja Kiršnerove igle,
Liječenje Hallux valgusa osteotomijom prve kosti metatarzusa po Krameru
primijenjena je fizikalna terapija (Nemetrodin i masaža) u toku dvije sedmice.
Nismo primijetili niti jedan
slučaj usporenog srastanja
kosti niti pseudoartorze. Pacijente smo operirali u općoj
anesteziji, uz postavljanje tournique. Pacijenti su mobilizirani prvog postoperativnog
dana uz oslonac na petu. Prvi
prevoj slijedio je prvog postoperativnog dana. Pacijente
smo otpuštali drugog do četvrtog postoperativnog dana. Slika 3a i 4a. Redgenski snimak učinjen prvog postoperativnog dana
Konci, kao i Kiršnerova igla
odstranjeni su na kontroli
hod. Nakon primjenjene Kramer osteomnogo bolje nego prije primjenom ratomije, pseudoartroze su srasle, tegobe
zličitih drugih metoda. Opisani se zasu prestale uz vrlo dobar rezultat. Istu
hvat danas najčešće primjenjuje na natehniku sa obrnutim procesom primješem odjeljenju u liječenju deformiteta
njivali smo uspješno kod varus defortipa halux valgus.
macije malog prsta stopala. U poređenju sa zahvatima na mehkim tkivima i
LITERATURA
1. Radojević S. Sistematska i topografska anatos raznim drugim osteotomijama na prmija, Noga, Medicinska knjiga, Beograd–Zavoj kosti međunožja, nakon kojih je bilo
greb, 1963.
i nezadovoljavajućih rezultata recidiva
2. Pernkopf E. Atlas der topographischen und
angewandten Anatomie des Menschen Urdeformiteta, Kramerovom tehnikom
ban—Schwarzenberg, München und Berlin
i metodom kirurškog liječenja defor1964, Zweiter Band.
miteta hallux valgus veoma smo zado3. Heim U, Pfeiffer KM. Periphere Osteosynthesen Springer-Verlag, Berlin – Heidel Berg–
voljni i za nas je ona praktičnol postala
New York, 1972
metodom izbora.
4. Edmondson AS, Crenshaw AH. Campbe5. ZAKLJUČAK
Slika 5. Kramer osteotomija ka digitus quinti
U periodu od 1984. do 1988. godine
kod 98 pacijenata sa deformitetom Halux valgus primijenili smo Kramerovu
osteotomiju na prvoj kosti međunožja.
Postigli smo veoma dobre rezultate,
varus
5. 6. 7. 8. ambulantno. Stopalo smo bandažirali
6 do 7 sedmica.
9. 4. DISKUSIJA
Za vrijeme boravka na Klinici „Balgrist“ u ZuRichu, ljubaznošću koleginice E. Lamprecht, prvi autor je imao
čast upoznati se s orginalnim radovima i publikacijama prof. J. Kramera
i E. Lamprechta. Od 1984. godine primjenjujemo taj zahvat u liječenju hallux
valgusa. Vrlo brzo svladali smo tehniku,
komplikacija nije bilo, a također nit u
jednog oboljelog nisu se pojavili pseudoartroza ili recidiv. Kod jedne pacijentice intervenirali smo na oba stopala zbog pseudoartroza prve metatarzalne kosti nakon Shevron operacije.
Bol, otok, onemogućavali su oslonac i
10. 11. 12. 13.
14.
15.
Slika 6. Rezultat osam sedmica postoperativno
lls operative Orthopaedics. The C.V. Mos by
Company, St. Louis -Toronto -London, 1980.
Lamprecht E, Kramer J. Die Metatrsale-IOsteo tomie nach Kramer zur Behandlung
des Halux valgus, Orthopädische Praxis, 1982;
636-45.
Muminagić S, Talić A, Alibegović A. Kramer
osteotomy in the treatment of hallux valgus
Acta orthopaedica, 1990;1:15-20.
Venore JV. Diagnosis and treatment of first
metatarsal Joint disorders; J Foot ankle Surg,
2003;42(3):112-23.
King DM. Associated Deformitites and hypermobilitiy In Halux valgus, Foot ankle int,
2004;25(4):251-5.
Ferrari J, Higins JP, Price TD. Interventionts
for Treating Hlaux valgus and bunions,. Corane Datebase Syst Rev. .2004.
Halux valgus, www.emedicine.com/orthoped/
topic16.htm
Bunions, www.wikipedia.org/wiki/bununion
Bunions, www.epodiatry.com/bunion.htmchaced
Radiographics evaluation of Hallux valgus
www.rawashington.edu/academics/academicsection/msk
Halux valguswww.aaep.org/afp/200201101/
tifs/8html
Halux valgus, www.medicine-berlin.de
Kontakt adresa autora. Prof. Dr. Sahib
Muminagić. Ortopedsko oboljenje Kantonalne
bolnice u Zenici. Zdravstveni fakultet
Univerziteta u Zenici. Tel.: 00 387 32 444 780.
MED ARH 2009; 63(3) • STRUČNI ČLANCI / PROFESSIONAL PAPERS
165
Perkutane koronarne intervencije bez „on-site“ kardiohirurške potpore
Perkutane koronarne intervencije
bez „on-site“ kardiohirurške potpore
Percutaneous Coronary Interventions Without On-Site Cardiac
Surgical Backup
Zoran Stajić1, Zdravko M. Mijailović2
Sala za kateterizaciju srca, Kliničko-bolnički centar Zemun, Beograd, Srbija1
Klinika za kardiologiju, Vojnomedicinska akademija, Beograd, Srbija2
Revijalni članak
SAŽETAK
Perkutane koronarne intervencije predstavljaju danas, tri decenije nakon prve balon angioplastike koronarnih
arterija, bezbedan, efikasan i najčešće primenjivani metod revaskularizacije miokarda. Prve perkutane koronarne intervencije bez „on-site“ kardiohirurgije počele su se izvoditi početkom devedesetih godina XX veka,
zahvaljujući unapređenju tehnike i materijala korišćenih za ove procedure, kao i zbog potrebe da se stanovnicima u udaljenim oblastima učini dostupnim ova savremena i efikasna terapija. Međutim, i danas posle skoro
dvadesetak godina izvođenja perkutanih koronarnih intervencija i u ustanovama bez kardiohirurgije ovo pitanje
ostaje kontroverzno i nerešeno. Tako da i pored postojanja velikog broja interventnih kardioloških centara
bez „on-site“ kardiohirurgije u velikom broju zemalja u kojima se izvodi značajan broj i elektivnih i primarnih
intervencija, zvanični vodiči asocijacija za perkutane koronarne intervencije i dalje ne preporučuju izvođenje intervencija bez postojanja „on-site“ kardiohirurgije. Ipak, u poslednje vreme fokus sa pitanja prisustva „on-site“
kardiohirurgije se sve više pomera u pravcu definisanja kriterijuma za izvođenje perkutanih koronarnih intervencija po najvišim standardima bez obzira na postojanje „on-site“ kardiohirurške potpore. U ovom revijalnom
radu dat je trenutni pregled aktuelnih stavova o organizaciji i izvođenju perkutanih koronarnih intervencija u
ustanovama bez kardiohirurške potpore.
Ključne reči: Perkutane koronarne intervencije, Centar bez „on-site“ kardiohirurgije, Bezbednost, Ishod
Review
SUMMARY
Percutaneous coronary interventions are now, three decades after the first balloon angioplasty of the coronary
arteries, safe, effective, and most commonly applied method of myocardial revascularization. The first percutaneous coronary intervention without “on-site” cardiac surgery began at the beginning of the nineties of the
twentieth century, thanks to the improvement of techniques and materials used for these procedures, as well
as the need to make available to citizens in remote areas modern and effective therapy. However, today, after
nearly twenty years of application of percutaneous coronary interventions in facilities without cardiac surgery
this issue remains controversial and unresolved. So despite the existence of a large number of interventional
cardiology centers without “on-site” cardiac surgery in a large number of countries in which they performed
a significant number of elective and primary interventions, the official guidelines of the associations for
percutaneous coronary interventions still does not recommend implementation of interventions without the
existence of “on –site” cardiac surgery. But, recently the focus shifts from the questions about presence of “onsite” cardiac surgery in the direction of defining criteria for performing percutaneous coronary interventions
according to the highest standards regardless of the existence of “on-site” cardiac surgical backup. This review
article gives the current view on current attitudes about the organization and implementation of percutaneous
coronary interventions in facilities without cardiac surgical backup.
Keywords: percutaneous coronary interventions, center without on-site cardiac surgical backup, safety, outcome
1. UVODNI DEO
U protekle tri decenije, nakon što je
1977. godine Andreas Grüntzig u univerzitetskoj bolnici u Cirihu izveo prvu perkutanu balon angioplastiku koronarnih
arterija, primena i indikacije za izvođenje ove metode su revolucionarno prošireni i unapređeni. Naročito u poslednjoj deceniji je došlo do značajnog usavršavanja tehnike perkutanih koronarnih intervencija (PCI), poboljšanja tehnoloških karakteristika materijala (kateteri, koronarne žice), daljeg napretka
u razvoju koronarnih stentova (poboljšanje dizajna i materijala, otkriće stentova obloženih lekovima), razvoja i usavršavanja novih naprava (aspiracioni kateteri, sredstva za trombektomiju), kao
i usavršavanja antiagregacione terapije.
Zahvaljujući tome, danas se perkutane
koronarne intervencije smatraju rutin166
skim, bezbednim i efikasnim načinom
lečenja i predstavljaju vodeći metod revaskularizacije miokarda u razvijenim
zemljama, sa približnim odnosom izvođenja 2:1 u odnosu na konvencionalnu
koronarnu bajpas hirurgiju (1, 2).
2. CILJ RADA
Cilj ovog rada je pregled aktuelne literature i stavova u pogledu organizacije
i izvođenja perkutanih koronarnih intervencija u ustanovama bez kardiohirurške službe, s obzirom na i dalje prisutna
kontroverzna mišljenja i brojne debate o
ovom pitanju.
3. METOD I REZULTATI RADA
Rad je revijskog karaktera. Korišćenjem sledećih engleskih ključnih reči:
percutaneous coronary intervention,
center without on-site cardiac surgical
MED ARH 2009; 63(3) • Revijalni članci • Reviews
backup, safety, and outcomes, pretražili
smo dostupnu literaturu na sajtu www.
ncbi.nlm.nih.gov/pubmed zaključno sa
mesecom julom 2009. godine. Aktuelne
preporuke američkih (ACC/AHA/SCAI)
i evropskih asocijacija za perkutane koronarne intervencije (EAPCI) smatrani
su bazičnim dokumentima u pripremi
ovog teksta.
3.1. Nastanak PCI centara bez „onsite“ kardiohirurške potpore
Potreba da se i stanovnicima u ruralnim, udaljenim oblastima SAD i Australije obezbede PCI, posebno bolesnicima
sa akutnim infarktom miokarda, kao najefikasnijem terapijskom modalitetu reperfuzije, dovela je do inicijalnog uspostavljanja programa interventne kardiologije u opštim bolnicama bez „on-site“
kardiohirurgije u ovim zemljama početkom devedesetih godina XX veka (3).
Međutim, ubrzo se pokazalo da je
iz razloga održivosti interventnog programa, a imajući u vidu i neophodan minimalan godišnji broj PCI [volumen] za
ustanove i operatore, bilo takođe neophodno ustanoviti pored hitnog i elektivni
PCI program u ustanovama bez „on-site“
kardiohirurgije. Na taj način je otvoreno
kontroverzno pitanje aspekta bezbednosti elektivnih PCI u ustanovama bez
kardiohirurgije, s obzirom da je rizik od
potrebe za hitnom kardiohirurškom intervencijom danas mali [<0.5%], ali ipak
postoji (4). Međutim, u poslednje vreme
primarno pitanje sve više ne predstavlja
problem nepostojanja „on-site“ kardiohirurgije koji se rešava brzim i efikasnim
transportom u kardiohirurški centar koji
obezbeđuje hiruršku potporu, već postizanje najvišeg kvaliteta PCI, nezavisno
od činjenice postojanja „on-site“ kardiohirurške potpore u zdravstvenom centru (5).
3.2. Prevalencija i trendovi PCI bez
„on-site“ kardiohirurgije
Prevalencija urađenih PCI bez kardiohirurške potpore se konstantno tokom
poslednjih petnaestak godina povećavala, kako u svetu, tako i u državama našeg regiona. Takođe, postojao je i stalni
trend povećanja broja PCI centara bez
kardiohirurške potpore. Prema podacima američkog CathPCI registra, 2005.
godine je u SAD postojalo 16.1% [75/463]
PCI centara bez kardiohirurške potpore
(6). U Velikoj Britaniji je 2004. godine,
čak 26% PCI centara radilo bez kardiohirurške potpore (7). Slični podaci postoje
i za druge ekonomski razvijene države.
U Srbiji, zaključno sa mesecom julom
Perkutane koronarne
intervencije bez „on-site“ kardiohirurške potpore
PRILOZI
2009. godine postojao je veći broj PCI
centara bez kardiohirurgije u odnosu
na broj centara sa kardiohiruškom potporom [5/9 PCI centara su bez kardiohirurške potpore]. U centrima bez kardiohirurgije u Srbiji je tokom 2008. godine
urađeno ukupno 25.4% [1944/7622] svih
PCI, odnosno ukupno 15.7% [264/1681]
svih primarnih PCI (8).
Realno je očekivati da se i u narednom periodu nastavi povećanje broja
urađenih PCI, posebno primarnih u
centrima bez kardiohirurgije. Takođe, u
Srbiji se planira otvaranje novih, regionalnih PCI centara bez kardiohirurgije.
3.3. Bezbednost i efikasnost
Do sada je publikovano oko 30-tak
studija koje su ispitivale bezbednost i
efikasnost PCI u centrima bez „on-site“
kardiohirurgije i sve osim jedne (9) su
pokazale jednaku bezbednost i efikasnost, odnosno neinferiornost PCI (10,
11, 12, 13, 14, 15, 16, 17, 18) urađenih u
centrima bez „on-site“ kardiohirurgije u
poređenju sa centrima sa „on-site“ kardiohirugijom. Ovo naravno važi samo za
PCI centre koji su intermedijarnog ili velikog volumena [>200 intervencija godišnje]; centri sa malim volumenom [<200
PCI/godišnje] imaju značajno lošije rezultate, tj. veći mortalitet (19). Efikasnost PCI u današnjoj eri stentova obloženih lekovima i savremene antiagregacione terapije kreće se oko 97%, dok je
incidencija velikih komplikacija <1%, a
s obzirom da se najveći broj komplikacija uspešno rešava perkutanim interventnim pristupom, potreba za hitnom
kardiohirurškom intervencijom tokom
PCI iznosi <0.5% (20).
Važno je istaći i da je nedostatak svih
dosadašnjih studija činjenica da su to bile
uglavnom retrospektivne, deskriptivne
studije pojedinačnih centara koji su svoje
rezultate poredili sa rezultatima velikih
„on-site“ centara. Za sada jedina, velika,
multicentrična, prospektivna, randomizovana studija koja ispituje bezbednost
i efikasnost PCI u centrima sa „on-site“
kardiohirurgijom u odnosu na centre
bez „on-site“ kardiohirurgije je C-PORT
studija koja je započeta 2006. godine u
SAD (21).
Objavljivanje prvih rezultata ove studije očekuje se tokom 2009. godine. Kako
su dosadašnje preporuke bile bazirane isključivo na manjim opservacionim studijama i konsenzusu eksperata, sa velikim nestrpljenjem se očekuju rezultati
ove studije koji bi mogli dovesti do promene sadašnjih preporuka.
Tabela 1. Klinički i angiografski kriterijumi koji označavaju visok interventni rizik
prema SCAI preporukama
I. Klinički kriterijumi čije prisustvo kod bolesnika označava potencijalno visoki rizik u
slučaju okluzije izazvane intervencijom:
• dekompenzovana zastojna srčana insuficijencija
• ejekciona frakcija leve komore ≤ 25%
• stenoza (>50%) glavnog stabla leve koronarne arterije ili trosudovna
koronarna bolest bez prethodne CABG
• pojedinačna stenoza koja ugrožava >50% preostalog vitalnog tkiva miokarda
II. Angiografski kriterijumi koji označavaju potencijalno visok rizik za nastanak
intervencijom izazvane akutne okluzije:
• difuzna bolest (>2cm u dužini stenoze) i izrazita tortuoznost proksimalnog
segmenta
• teško kalcifikovane lezije proksimalnog segmenta
• lezije na ekstremno velikim krivinama (>90°)
• nemogućnost protekcije velikih bočnih grana
• lezije na degenerativno izmenjenim starim venskim graftovima
• trombotične lezije
• bilo koje druge karakteristike lezije / arterije koje onemogućavaju
implantaciju stenta
• agresivni pristup u otvaranju CTO može dovesti do perforacije koronarne
arterije
SCAI, Society for Cardiovascular Angiography and Interventions; CABG, Coronary
Artery Bypass Grafting; CTO, Chronic Total Occlusion
3.4. Aktuelne preporuke za PCI bez
„on-site“ kardiohirurgije
Prema aktuelnom ACC/AHA/SCAI
vodiču iz 2007. godine (1), primarne
PCI u centrima bez kardiohirurgije i dalje nose indikaciju klase Iib, tj. mogu se
izvoditi pod određenim okolnostima,
dok elektivne PCI bez kardiohirurške
potpore imaju indikaciju klase III, tj. ne
preporučuju se.
Evropsko udruženje kardiologa u
svom vodiču za PCI iz 2005. godine (2)
se ne bavi pitanjem izvođenja PCI bez
kardiohirurške potpore kao ni pitanjima
vezanim za kompetentnost operatora,
opremljenosti i volumena ustanova.
Vodič britanskog udruženja za kardiovaskularne intervencije iz 2005. godine (7) podržava izvođenje PCI u centrima bez kardiohirurške potpore uz
poseban naglasak na utvrđivanje zajedničkih standarda za centre sa i bez kardiohirurgije.
Vodič belgijske radne grupe za invazivnu kardiologiju publikovan još 2003.
godine (22) posebno naglašava da „sadašnja standardna praksa za izvođenje
elektivnih PCI ostaje prisustvo kardiohirurške potpore“.
Kardiološko udruženje Australije i
Novog Zelanda u svom vodiču publikovanom 2005. godine (23) navodi da se
„PCI prvenstveno izvode u centrima sa
on-site kardiohirurškom potporom, ali
se i potvrđuje da zahtevi za obezbeđivanje kardiohirurgije mogu biti16izuzeti
u određenim okolnostima i da adekvatno
obučeni operatori mogu bezbedno izvoditi interventne koronarne procedure u
bolnicama bez kardiohirurške potpore“.
Takođe, u dokumentu se navodi da pacijentima u udaljenim oblastima, koji
imaju smanjenu dostupnost korišćenja
savremene interventne kardiološke terapije, omogućavanje dostupnosti interventnih procedura treba da poboljša
kvalitet zdravstvene zaštite.
Interesantno je navesti primer Nemačke, zemlje sa bogatom tradicijom i
odličnom organizacijom zdravstvene zaštite u kojoj ne postoje nacionalne preporuke za izvođenje PCI, mada postoji
značajan broj operativnih interventnih
kardioloških centara bez „on-site“ kardiohirurške potpore.
U Srbiji do sada nisu publikovane nacionalne preporuke vezane za standarde
izvođenja koronarnih angiografija i PCI.
MED ARH 2009; 63(3) • Revijalni članci • Reviews
167
Perkutane koronarne intervencije bez „on-site“ kardiohirurške potpore
Takođe, trenutno ne postoje ni preporuke za organizaciju i izvođenje PCI u
centrima bez kardiohirurgije.
Imajući u vidu trenutno i dalje kontroverzni status izvođenja PCI u centrima bez kardiohirurške potpore, koje
se uprkos nepostojanju jasnih preporuka
izvode u velikom broju zemalja i u sve većem broju, američko udruženje za kardiovaskularne angiografije i intervencije
(SCAI) je 2007. godine publikovalo dokument zasnovan na konsenzusu eksperata iz različitih zemalja o izvođenju PCI
bez kardiohirurške potpore (20). U izradi
ovog dokumenta učestovali su isključivo eksperti koji rade u PCI centrima
sa „on-site“ kardiohirurškom potporom
kako bi se izbegao potencijalni konflikt
interesa. Cilj ovog dokumenta nije bio
ni da favorizuje ni da negira izvođenje
PCI bez kardiohirurške potpore, već da
u trenutno kontraverznoj situaciji u kojoj
zvanični vodiči uglavnom ne odobravaju
elektivne PCI u centrima bez „on-site“
kardiohirurške potpore koje se u stvarnosti izvode u značajnom, i sve većem
broju, definiše adekvatne i neophodne
standarde, kako bi operatori u PCI centrima bez „on-site“ kardiohirurške potpore radili po jasno definisanim, najvišim standardima.
3.5. Kompetentnost operatora
Samo izvođenje velikog broja intervencija, mada neophodno, samo po sebi
ne garantuje i visoki kvalitet rada operatora. Šta više, smatra se da je značajnija
mera kvaliteta odnosno kompetentnosti
operatora, broj komplikacija i proceduralni i klinički ishod bolesnika. Prema
SCAI preporukama (20), operatori u PCI
centrima bez „on-site“ kardiohirurgije
treba da ispunjavaju, pored generalnih
ACC/AHA kriterijuma za sertifikaciju
(1), i dodatne kriterijume:
•• broj komplikacija i ishod bolesnika
treba da bude za svakog operatora
najmanje ekvivalentan, a idealno i
superioran, u poređenju sa vrednostima na nacionalnom nivou,
•• za svakog operatora je neophodno
da postoji proverljiv dosije sa ishodima bolesnika, što je od većeg značaja od arbitrarno određenog broja
neophodnih procedura,
•• pre započinjanja rada u centru bez
„on-site“ kardiohirurgije, operator treba da ima iza sebe urađenih najmanje 500 intervencija kao
prvi operator nakon završenog treninga; za operatore sa urađenim
manjim brojem intervencija ne168
ophodan je mentorski rad i monitoring dok se njihove sposobnosti,
odluke i ishodi bolesnika ne procene i formalno potvrde da su ekvivalentni nacionalnim vrednostima,
•• ukupan godišnji broj intervencija
smatra se da za operatore u centrima bez „on-site“ kardiohirurgije
treba da bude nešto viši od broja
za operatore u centrima sa kardiohirurgijom, drugim rečima ovim
operatorima je potrebno veće iskustvo zbog rešavanja eventualnih
komplikacija.
Kao što se iz napred navedenog može
zaključiti, za operatore u centrima bez
„on-site“ kardiohirurgije potrebno je
veće prethodno iskustvo i konstantno
održavanje kompetentnosti putem većeg broja intervencija na godišnjem nivou uz kontinuiranu edukaciju.
3.6. Kvalifikacije centra i ostalog
osoblja
Neobično je važno da i celokupno
osoblje u Sali za kateterizaciju srca, kao
i u koronarnoj jedinici bude u potpunosti edukovano u pogledu tretmana pacijenata pre, tokom i posle procedure.
Edukacija podrazumeva poznavanje
svih mera u slučaju potencijalnih proceduralnih komplikacija uključujući i primenu lekova, DC šoka, intraaortne balon pumpe, pacemakera, kao i svih ostalih mogućnosti perkutanog interventnog
rešavanja komplikacija (24).
U SAD se smatra da je neophodan
mininalni broj 200 PCI godišnje da bi
centar bez „on-site“ kardiohirurgije bio
operativan. Manji broj intervencija se
eventualno može dozvoliti u veoma udaljenim oblastima. Apsolutni minimum
u SAD je 150 PCI/godišnje, od čega 36
primarnih PCI; centri koji nemaju ovaj
volumen intervencija ne mogu imati licencu za rad (25). Međutim, novootvoreni PCI centri imaju period od dve godine na raspolaganju da dostignu neophodan apsolutni minimum intervencija.
Ukoliko nakon toga ne uspeju da dostignu ovaj broj moraju prestati sa radom (20).
Svrha organizovanja PCI programa u
centrima bez „on-site“ kardiohirurgije je
izvođenje pre svega primarnih PCI (26).
Iz tog razloga se u SAD ne dozvoljava
otvaranje centara u kojima će se izvoditi
samo elektivne PCI; svaki PCI centar u
SAD bez „on-site“ kardiohirurgije je u
obavezi da izvodi primarne PCI 24h/svakodnevno. PCI centri bez „on-site“ kardiohirurgije u Evropi, kao i u našoj zemlji
MED ARH 2009; 63(3) • Revijalni članci • Reviews
trenutno nemaju obavezu da obezbeđuju
primarne PCI 24h/svakodnevno već je
to stvar organizacije na nivou ustanove
i svake zemlje pojedinačno.
3.7. Selekcija bolesnika i lezija
Brižljiva primena kliničkih i angiografskih kriterijuma je neophodna za
selekciju bolesnika pre izvođenja elektivnih PCI u centrima bez „on-site“ kardiohirurške potpore. Naime, u slučaju
elektivnih PCI, bolesnik ima mogućnost da bira i centar i operatora. Situacija je drugačija u slučaju akutnog infarkta miokarda i primarnih PCI. Drugim
rečima, klinička slika i odnos korist-rizik
su različiti za elektivne i primarne PCI,
iz čega proizlazi da u ovim slučajevima
treba primeniti i različite kriterijume.
Kod izvođenja elektivnih PCI bez
„on-ste“ kardiohirurške podrške, potrebno je proceniti ne samo verovatnoću neuspeha PCI već i potencijalni
rizik u slučaju nastanka komplikacija.
Naime, s jedne strane postoje nisko odnosno visoko rizični bolesnici [prisustvo
komorbiditeta, na pr. terminalna bubrežna insuficijencija, malignomi, loša
rezidualna kardijalna funkcija i sl.], dok
s druge strane postoje nisko odnosno visoko rizične lezije [na pr. lezije na glavnom stablu leve koronarne arterije, ostijalne i bifurkacione lezije, trombotične
lezije, hronične totalne okluzije, lezije
na degenerativno izmenjenim venskim
graftovima i sl.]. Važno je uvek istovremeno proceniti i anticipirati rizičnost i
bolesnika i lezije kod izvođenja elektivnih PCI u centrima bez „on-site“ kardiohirurške podrške.
Kao što je već istaknuto PCI centar
bez kardiohirurgije mora osim primarnih izvoditi i elektivne PCI, s tim što kod
svakog bolesnika treba pre elektivne PCI
individualno proceniti rizik. Trenutno
postoji nekoliko efikasnih i jednostavnih modela za procenu rizika kod kojih
se na osnovu kliničkih i angiografskih
parametara izračunava rizik skor koji
predstavlja verovatnoću rizika nastanka
smrtnog ishoda tokom PCI (27-29).
U tabeli 1. prikazani su klinički i angiografski kriterijumi koje SCAI (20) definiše kao visoko rizične. U tabeli 2. su
prikazane SCAI preporuke za izvođenje
elektivnih PCI u centrima bez „on-site“
kardiohirurgije (20). U praksi su moguće
četiri kombinacije [tabela 2.]. Za centar
bez „on-site“ kardiohirurgije idealan bolesnik za PCI je nisko rizični sa nisko rizičnom lezijom. Kod visoko rizičnih bolesnika sa visoko rizičnim lezijama elek-
Perkutane koronarne intervencije bez „on-site“ kardiohirurške potpore
tivne PCI treba izvoditi u centrima sa
„on-site“ kardiohirurškom podrškom, a
u određenim slučajevima i uz kardiohirurški „stand-by“ [pripravnost kardiohirurga i sale za vreme PCI]. Pri izvođenju
elektivne PCI kod visoko rizičnog bolesnika sa nisko rizičnom lezijom u centru
bez „on-site“ kardiohirurgije, preporuka
je da se o tome obavestiti nadležni kardiohirurški centar koji obezbeđuje „offsite“ potporu radi pripravnosti u slučaju
nastanka komplikacija. Za PCI tretman
visoko rizičnih lezija kod nisko rizičnih
bolesnika u centru bez „on-site“ kardiohirurgije dovoljno je pridržavati se standardnih mera.
3.8. Hitan transport u kardiohirurški
centar u slučaju komplikacija
Za uspešnost i bezbednost PCI programa u centrima bez „on-site“ kardiohirurške potpore neophodna je tesna
saradnja i stalna komunikacija sa kardiohirurškim centrom koji obezbeđuje
podršku. Ova saradnja treba da bude
bazirana na formalizovanom i potpisanom sporazumu između dve ustanove
tj. između PCI centra bez kardiohirurgije i kardiohirurškog centra koji pruža
potporu Ključna odrednica sporazuma
treba da bude protokol za hitan transport
bolesnika u slučaju potrebe za hitnom
kardiohirurškom intervencijom; idealno
bi bilo da se transfer periodično simulaciono testira (20).
U informisanom pristanku koji bolesnici daju neposredno pre koronarografije i PCI, treba da stoji da će u slučaju
iznenadnog nastanka komplikacija tokom ovih procedura koje zahtevaju neodložno hirurško zbrinjavanje biti hitno
transportovani u određeni kardiohirurški centar sa kojim postoji prethodni
sporazum. S druge strane, formalno potpisivanje saglasnosti i na hiruršku intervenciju pre koronarografije i PCI danas
se ne smatra više neophodnim (30), s obzirom da ova potreba postoji u izrazito
malom broju slučajeva. Osim toga danas u velikim kardiovaskularnim centrima koji imaju „on-site“ kardiohirurgiju takođe više ne predstavlja standard
da hirurška sala i kardiohirururški tim
budu pripravni odnosno „stand-by“ za
vreme rutinskih PCI. Zbog niske incidencije komplikacija za čije rešavanje je
potrebna kardiohirurška intervencija,
ne postoje precizni podaci o potrebnom
vremenu za transport bolesnika iz PCI
sale u kardiohiruršku salu u centrima sa
„on-site“ kardiohirurgijom, ali se pretpostavlja da je potrebno oko 60 min da se
Tabela 2. SCAI preporuke za izvođenje elektivnih PCI u centrima bez „on-site“
kardiohirurgije
Visok klinički, visok angiografski rizik:
Ne preporučuje se PCI u centru bez „onsite“ kardiohirugije
Visok klinički, nizak angiografski rizik:
PCI u centru bez „on-site“ kardiohirugije
sa pripravnom „off-site“ podrškom
Nizak klinički, visok angiografski rizik:
PCI u centru bez „on-site“ kardiohirurgije
uz standardnu proceduru
Nizak klinički, nizak angiografski rizik:
PCI u centru bez „on-site“ kardiohirurgije
Najbolji scenario
SCAI, Society for Cardiovascular Angiography and Interventions; PCI, Percutaneous
Coronary Intervention
Skraćenice i objašnjenja skraćenica korišćenih u radu
On-site
- u istoj ustanovi
Off-site
- u drugoj ustanovi
PCI
- percutaneous coronary intervention
CABG
- coronary artery bypass grafting
DC
- direct current
CTO
- chronic total occlusion
ACC
- American College of Cardiology
AHA
- American Heart Association
SCAI
- Society for Cardiovascular Angiography and Intervention
ESC
- European Society of Cardiology
Kontak adresa autora: Doc. dr Zdravko M. Mijailović, Vojnomedicinska
okupi kardiohirurški tim i pripremi hi- vremene standarde u lečenju i nezi.
akademija, Klinika za kardiologiju, Crnotravska 17, 11000 Beograd, Srbija, Tel:
rurška
sala. Iz tog razloga preporučeno
3.9. Praćenje kvaliteta rada
+381-11-2661-129.
Fax: +381-11-2666-164,
Mobilni:
+381-63-248-800,
E-mail:
vreme
transporta bolesnika
iz PCI cenIz
dosadašnje
kliničke prakse
je potra bez kardiohirurgije u nadležni
karstalo
jasno
da
za
kvalitet
izvedenih
PCI
mdzdravko@yahoo.com
diohirurški centar treba da bude 60-120 nije najvažnije prisustvo „on-site“ karmin (20). U slučaju pojave komplikacija diohirurške potpore. Smatra se da je
tokom PCI u centru bez „on-site“ kardi- osim neophodne tehnološke opremljeohirurgije za čije efikasno zbrinjavanje bi nosti Sale za kateterizaciju srca i iskumogla biti neophodna i kardiohirurška stva operatora, za kvalitet programa inintervencija, neophodno je odmah oba- terventne kardiologije mnogo značajnije
vestiti nadležni kardiohirurški centar, kontinuirano praćenje kvaliteta rada što
17
čak i ako se inicijalno pokuša perkutano se postiže formiranjem elektronske baze
interventno zbrinjavanje, kako se ne bi podataka – registra, u koju se unose regubilo dragoceno vreme odnosno kako dovno podaci o pacijentima i učinjenim
bi se odmah po transportu bolesnika u intervencijama. Bolnički PCI registar
kardiohirurški centar, bez daljeg zadr- treba da sadrži demografske i kliničke
žavanja, moglo pristupiti neodložnoj podatke o bolesnicima, precizne podatke
hirurškoj intervenciji. Osim neophodne o intervencijama i eventualnim komplisaradnje u aktivnom lečenju kompliko- kacijama, kao i proceduralni i klinički isvanih i naročito teških bolesnika, od- hod za svakog bolesnika posle urađene
nosno u lečenju komplikacija, saradnja PCI. Neophodno je stalno praćenje i pointerventnih kardiologa i kardiohirurga ređenje podataka iz bolničkog PCI repodrazumeva i aktivno učestvovanje na gistra u odnosu na utvđene nacionalne
zajedničkim konferencijama i sesijama standarde [nacionalni PCI registar] kao
posvećenim rešavanju komplikacija to- i u odnosu na podatke iz vodećih nacikom PCI. Samo na ovaj način, timskim onalnih PCI centara sa „on-site“ kardipristupom, moguće je postići najviše sa- ohirurgijom. Podatke iz bolničkih i naMED ARH 2009; 63(3) • Revijalni članci • Reviews
169
Perkutane koronarne intervencije bez „on-site“ kardiohirurške potpore
cular Intervention Society and the British
Cardiac Society. Coronary angioplasty:
guidelines for good practice and training.
Heart. 2005;91(Suppl VI):vi1-vi27.
Cath-lab reports for 2008. 5th Belgrade
Summit of Interventional Cardiologists.
Syllabus 2009; 162-3.
9. Wennberg DE, Lucas FL, Siewers AE,
Kellett MA, Malenka DJ. Outcomes of percutaneous coronary interventions performed at centers without and with onsite coronary artery bypass graft surgery. JAMA.
2004;292:1961-8.
10. Djelmami-Hani M, Mouanoutoua M, Hashim A, Solis J, Bergen L, Oldridge N, et
al. Elective percutaneous coronary intervention without on-site surgical backup:
a community hospital experience. WMJ.
2007;106:481-5.
11. Frutkin AD, Mehta SK, Patel T, Menon
P, Safley DM, House J, et al. Outcomes of
1,090 consecutive, elective, nonselected
percutaneous coronary interventions at
a community hospital without onsite cardiac surgery. Am J Cardiol. 2008;101:53-7.
12. Peels JOJ, Hautvast RWM, de Swart JBRM,
Huybregts MAJM, Umans VAWM, Arnold
AER, et al. Percutaneous coronary intervention without on site surgical back-up;
two years registry of a large Dutch community hospital. Int J Cardiol. 2009;132:59-65.
13. Herman BA, Iyer RN, Godier KJ. Safety
and efficacy of offsite percutaneous coronary interventions in 1,348 consecutive
patients in rural Tasmania. Am J Cardiol.
2008;102:1323-7.
14. Ting HH, Raveendran G, Lennon RJ, Long
KH, Singh M, Wood DL, et al. A total of
1,007 percutaneous coronary interventions without onsite cardiac surgery; acute
and long-term outcomes. J Am Coll Cardiol. 2006;47:1713-21.
15. Brown DC, Mogelson S, Harris R, Kemp
D, Massey M. Percutaneous coronary interventions in a rural hospital without surgical backup: report of one year of experience. Clin Cardiol. 2006;29:337-40.
16. Melberg T, Nilsen DWT, Larsen AI, Barvik S, Bonarjee V, Kuiper KKJ, et al. Nonemergent coronary angioplasty without onsite surgical back-up: a randomized study
evaluating outcomes in low-risk patients.
Am Heart J. 2006;152:888-95.
17. Paraschos A, Callwood D, Wightman MB,
Tcheng JE, Phillips HR, Stiles GL, et al.
Outcomes following elective percutaneous coronary intervention without on-site
surgical backup in a community hospital.
Am J Cardiol. 2005;95:1091-3.
18. Gunalingam B, Bates F, Wilkes N, Hill A,
Wang D. Percutaneous coronary interventions without on-site cardiac surgery: a remote Australian experience. Heart Lung
Circulation. 2008;17:388-94.
19. Brindis RG, Weintraub WS, Dudley RA.
Volume as a surrogate for percutaneous coronary intervention quality: is this
the right measuring stick? Am Heart J.
2003;146:932-4.
20. Dehmer GJ, Blankenship J, Wharton TP,
Seth A, Morrison DA, DiMario C, et al. The
current status and future direction of per-
cionalnih PCI registara bi trebalo periodično da kontrolišu nezavisne agencije
ili institucije kako bi se osigurao najviši
kvalitet rada i integritet celokupnog pro- 8. cesa (20).
4. ZAKLJUČAK
I elektivne i primarne perkutane koronarne intervencije u centrima bez „onsite“ kardiohirurške potpore uz ispunjenost svih neophodnih standarda u pogledu kompetentnosti operatora, kvalifikacije centra i ostalog osoblja, uz postojanje efikasnog protokola za hitan transport bolesnika u kardiohirurški centar u
slučaju nastanka komplikacija, brižljivu
selekciju bolesnika i lezija, uprkos nepostojanju jasnih zvaničnih preporuka
predstavljaju danas široko primenjivan,
bezbedan i efikasan način revaskularizacije miokarda.
Fokus sa pitanja bezbednosti PCI u
centrima bez „on-site“ kardiohirurgije
je u poslednje vreme u velikoj meri pomeren ka pitanjima vezanim za pružanje
PCI po najvišim standardima nevezano
za postojanje „on-site“ kardiohirurgije.
LITERATURA
1. King SB, Smith SC, Morrison DA, Williams DO, Hirshfeld JW, Jacobs AK, et al.
Focused update of the ACC/AHA/SCAI
2005 guideline update for percutaneous
coronary intervention. J Am Coll Cardiol.
2007;2008:51.
2. Silber S, Albertsson P, Avilés FF, Camici
PG, Colombo A, Hamm C, et al. Guidelines for percutaneous coronary interventions: the task force for percutaneous coronary interventions of the European Society of Cardiology. 2005;26:804-47.
3. Dehmer GJ. Percutaneous coronary intervention without onsite surgical backup.
Curr Cardiol Rep. 2008;10:407-14.
4. Javaid A, Buch AN, Satler LF, Kent KM,
Suddath WO, Lindsay J, et al. Management
and outcomes of coronary artery perforation during percutaneous coronary intervention. Am J Cardiol. 2006;98:911-4.
5. Kutcher MA, Klein LW, Ou Wharton TP,
Dehmer GJ, Singh M. et al. Percutaneous
coronary interventions in facilities without cardiac surgery on site. A report from
National Cardiovascular Data Registry
(NCDR). J Am Coll Cardiol 2009;54:16-24.
6. Dehmer GJ, Kutcher MA, Dey SK, Shaw
RE, Weintraub WS, Mitchell K, et al.
Frequency of percutaneous coronary interventions at facilities without on-site
cardiac surgical back-up – a report from
the American College of Cardiology – national cardiovascular data registry (ACCNCDR). Am J Cardiol. 2007;99:329-32.
7. Dawkins KD, Gerchlick T, de Belder M,
Chauhan A, Venn G, Schofield P, et al. Joint working group on percutaneous coronary intervention of the British Cardiovas-
170
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cutaneous coronary intervention without
on-site surgical backup: An expert consensus document from the society for cardiovascular angiography and interventions.
Catheter Cardiovasc Inter. 2007;69:471-8.
21. Aversano T. Angioplasty waiver controversy. Physicians News Digest, November
2006. [Available at http://www.physiciansnews.com/cover/1106csnj.htlm]
22. Legrand V, Wijns W, Vandenbranden F,
Benit E, Boland J, Claeys M, et al. Guidelines for percutaneous coronary intervention by the Belgian working group on invasive cardiology. Acta Cardiol. 2003;58:3418.
23. Brieger D. Policy on performance of coronary angiography and percutaneous coronary intervention in rural sites. The council of the Cardiac Society of Australia and
New Zealand, November 25, 2005. [Available at http://www.csanz.edu.au/guidelines/practice/index.htlm]
24. Bashore TM, Bates ER, Kern MJ, Berger
PB, Laskey WK, Clark DA, et al. ACC/
SCAI clinical expert consensus document on cardiac catheterization laboratory standards: summary of a report of the
ACC task force on clinical expert consensus documents. Cathet Cardiovasc Interv.
2001;53:281-6.
25. Singh M. The predicament of offering elective percutaneous coronary intervention at
sites without on-site cardiac surgery. Am
Heart J. 2006;152:810-1.
26. Peels HO, de Swart H, Ploeq TV, Hautwast RW, Cornel JH, Arnold AE, et al.
Percutaneous coronary intervention with
off-site cardiac surgery backup for acute
myocardial infarction as a strategy to reduce door-to-balloon time. Am J Cardiol.
2007;100:1353-8.
27. Wu C, Hannan EL, Walford G, Ambrose
JA, Holmes DR, King SB, et al. A risk score
to predict in-hospital mortality for percutaneous coronary interventions. J Am Coll
Cardiol. 2006;47:654-50.
28. Singh M, Rihal CS, Lennon RJ, Spertus J,
Rumsfeld JS, Holmes DR. Bedside estimation of risk from percutaneous coronary
intervention: the new Mayo Clinic risk
scores. Mayo Clinc Proc. 2007;82:701-8.
29. Moscucci M, Kline-Rogers E, Share D,
O’Donnell M, Maxwell-Eward A, Meengs
WL, et al. Simple bedside additive tool
for prediction of in-hospital mortality after percutaneous coronary interventions.
Circulation. 2001;104:263-8.
30. Arnold JR, Karamitsos T, Shirodaria C,
Banning AP. Should patients undergoing PCI still be consented for emergency
bypass? Int J Cardiol. (2007) doi.10.1016/
jjcard.2007.08.097.
Kontakt adresa autora: Doc. dr. Zdravko M.
Mijailović, Vojnomedicinska akademija, Klinika
za kardiologiju, Crnotravska 17, 11000 Beograd,
Srbija, Tel: +381-11-2661-129. Fax: +381-112666-164, Mobilni: +381-63-248-800, E-mail:
mdzdravko@yahoo.com
Pineal Region Tumors – Neurosurgical Review
Pineal Region Tumors –
Neurosurgical Review
Ivan Radovanovic1, Kemal Dizdarevic2, Nicolas de Tribolet1, Tarik Masic3, Sahib Muminagic4
Division of Neurosurgery, Geneva University Hospital, University of Geneva, Switzerland1
Department of Neurosurgery, Clinical Center of University of Sarajevo, Bosnia and Herzegovina2
Clinic for Maxilophacial surgery, Clinical center of University of Sarajevo, Bosnia and Herzegovina3
Department of General surgery, Cantonal hospital Zenica, Bosnia and Herzegovina4
Review
SUMMARY
The treatment for the pineal region tumors depends on tumor histology. Nowadays, germinomas can be cured
by radiotherapy and chemotherapy without surgical resection but the other pineal region tumors should be
primary treated by surgery. Two microsurgical approaches, the infratentorial supracerebellar and the occipital
transtentorial, are accepted as the main standard accesses to the pineal region. For benign pineal tumors
(pineocytoma, meningioma, mature teratomas, symptomatic pineal cysts, etc.) radical surgical resection can be
curative. For malignant tumors radical surgical resection is not an objective. Serum and CSF markers contribute
to the diagnosis of pineal parenchymal tumors. b-HCG is mainly positive in choriocarcinomas, embryonal carcinomas and mixed germ cell tumors and AFP is expressed by yolk sac tumors, embryonic carcinomas, immature
teratomas and mixed germ cell tumors. b-HCG is usually low in germinomas which are often positive for PLAP
on immunohistochemistry. Fifty-one pineal region tumors were surgically treated by senior author (NdT). Only
17 of them were the neoplasms originating from pineal body (pineal tumors). In conclusion it can be stressed
that management of pineal tumors requires a multidisciplinary cooperation. With the exception of germinoma
where only a biopsy is needed, the role of the surgeons still remains prominent as resection of pineal tumors
requires high technical skill and experience as well as precise clinical judgment.
Keywords: neurosurgery, pineal region tumors
1. Introduction
Pineal region tumors include a variety of neoplasms of different histological
origin growing from the pineal gland itself or from structures of the parapineal
space. These tumors are rare and account
for 0.4 to 1.0 % of intracranial tumors in
adults and 3-8 % in children . The most
common types are germ cell tumors, pineal parenchymal cell tumors and glial
cell tumor. Other pineal region tumors
such as meningiomas, PNET, neurocytomas, hemangioblastomas, cavernomas
and metastasis are infrequent.
The treatment options for the different pineal region tumors vary according
to their histological nature. However,
with the exception of germinomas which
can be nowadays cured by low-dose radiotherapy and chemotherapy and only
require a biopsy for diagnosis, surgery
still plays a central role in the management of most of the other pineal region
tumors followed or not by adjuvant radiotherapy, chemotherapy or a combination of both. The first successful removal
of a pineal tumor was reported in 1913 by
Oppenheim and Krause. Krause was the
first to describe and successfully use the
infratentorial supracerebellar approach
in three cases in 1926(1)..In the microsurgical era, Stein further developed and
popularized this approach during the
1970’s (2). Finally the right suboccipital
approach was described by Poppen and
further modified by Jamieson in 1971(3)..
The infratentorial supracerebellar and the occipital transtentorial approaches are nowadays accepted as the
main standard accesses to the pineal
region.
2. Microsurgical anatomy
Pineal region tumors lie deep in
the center of the cranium and are surrounded by critical anatomical structures that have to be respected at all
costs. Therefore, a precise knowledge of
the complex anatomy of the pineal region is of paramount importance (4, 5, 6).
The pineal gland is located on the midline and forms an appendix of the caudal
end of the diencephalons embracing the
pineal recess of IIId ventricule. The pineal stem is continuous with the habenular commissure dorsally and the posterior commissure ventrally. The pineal
body projects posteriorly in the quadrigeminal cistern where it is flanked by the
splenium of the corpus callosum superiorly and lies on the tectal quadrigeminal plate in-between the left and right
superior colliculi. The pineal gland is
mainly vascularized by the medial and
lateral posterior choroidal arteries. The
medial posterior choroidal arteries are
branches of the posterior cerebral artery
and in addition to the pineal body they
supply the superior and inferior colliculi, and the choroidal plexus of the third
ventricule. These arteries are displaced
laterally by pineal tumors in the cistern
and rostrally in the posterior part of the
third ventricule together with internal
cerebral veins. The posterior lateral choroidal artery supplies the pulvinar and
is generally displaced laterally by pineal
tumors. Other important arterial landmarks are the superior cerebellar arteries that can be displaced inferiorly by pineal tumors and the medial occipital artery branching from the posterior cerebral artery and giving the calcarine artery. During surgical approaches to the
pineal gland, the major anatomical obstacle is the Galenic venous system. The
vein of Galen has several tributaries: the
superior vermian vein and the precentral
cerebral vein run in the midline and into
the dorsocaudal part of the great vein.
The internal cerebral veins and the pineal veins join ventrally. In pineal tumors, the posterior portion of the internal cerebral veins is always elevated
rostrally, and the veins are occasionally
separated from each other. On the lateral aspect of the great vein, the medial
occipital veins, the third segment of the
basal veins of Rosenthal, and the posterior mesencephalic veins join. The pineal veins are the draining veins of pineal tumors and drain into either the
posterior portion of the internal cerebral veins or the vein of Galen. At this
point pineal tumors are thightly adherent to the internal cerebral vein and/or
the vein of Galen. An injury to the basal
veins or the internal cerebral veins will
yield major complications. And a transection of a major medial occipital vein
may cause homonymous hemianopsia or
visual seizures.
3. Rationale
For benign pineal tumors (pineocytoma, meningioma, neurocytomas, mature teratomas, hemangioblastomas,
cavernous hemangiomas, gangliogliomas, and symptomatic pineal cysts) total surgical resection is a primary goal
as surgery alone can be curative (7, 6)..
For malignant tumors surgery is only a
part of the treatment which will consist
of adjuvant therapies and therefore radical surgical resection is not an objective
(6, 8)..In all cases focus should be given
to reduce post treatment morbidity.
4. Decision making
a) Diagnosis
Clinical presentation: Symptomatic
MED ARH 2009; 63(3) • Revijalni članci • Reviews
171
homogenous cyst content with a thin enhancing
rim and
have
no or only mild
is compatible
with
an asymptomatic
benignmass
pineal cyst and the serum and CSF
markers
are
negative,
the
patient
can
be
followed
up without treatment. The treatment
effect on surrounding structures. Except for pineal region meningiomas or
of
other
pineal
tumors
requires
surgery
but
the
choice
of radical or conservative
falcotentorial notch meningioma extending inPineal
the Region
pineal
region,
angiography
is
Tumors
– Neurosurgical
Review
resection will depend on the diagnosis of the pre-surgical biopsy or the intraoperative
usually not necessary(6)..
frozen section. Benign tumors such as mature teratomas, pineocytomas or
pressed
yolk sac
tumors
(high levmeningiomas require radical surgical resection
whenby
feasible
without
compromising
els),
embryonic
carcinomas,
immature
surrounding neurovascular structures. More aggressive tumors, such as malignant
teratomas
and
mixed
germ
cell
tumors.
teratomas, pinealoblastomas, embryonal carcinomas, choroicarcinomas and yolk
sac
b-HCGtherapy
is usually
low in germinomas
tumors require a combination of surgery, radiation
and chemotherapy.
In any
which surgical
are often
positiveeven
for at
PLAP
on
case the prime goal of surgery should be avoiding
morbidity
the cost
immunohistochemistry
of a less radical surgical resection. The choice
of approach is a matter(8)..
of evaluating
Biopsy: Histological
is obthe anatomical relation of the tumor with the surrounding
structures. diagnosis
A steep angle
of
the straight sinus makes the infratentorial supracerebellar
difficultor
as endoan
tained eitherapproach
by stereotactic
extensive retraction of the cerebellum is required
visualize and reachbiopsy
the pineal
scopictotransventricular
or diarea. Moreover, in that case the lateral exposure
of during
the surgical
is restricted
and
rectly
openfield
surgery.
For large
renders the resection of larger tumors more complicated.
Evaluating
the relationship
pineal tumors
a stereotactic
biopsy is a
of the tumor with the quadrigeminal plate issafe
alsoinitial
important.
For smaller
midline
procedure
to obtain
diagnotumors located in the posterior part of the third
andextending
displacinginto
the the possis. ventricle
For tumors
quadrigeminal plate and the tegmentum of the
midbrain
infratentorial
terior
part ofcaudally,
the thirdthe
ventricule,
endosupracerebellar approach is favored as it allows
simple,
direct
and
symmetrical
scopic transventricular biopsy allows acexposure of the walls of the third ventricle and
cerebral
onasboth
sides.
cessinternal
to tumor
tissueveins
as well
third
ven1a. preoperative MRI
1b. postoperative MRI
In the case the tumor lies more caudally andtriculostomy
extends in thetoupper
portion
of
the
treat hydrocephalus (6)..
Figure 1a
and
1b.:
Sagittal
MRI
section
(T1+gadolinium)
of
a
pineal
lesion
removed
by
NdT
through
Figure 1A and 1B. Sagittal MRI section (T1+gadolinium)
of a pineal
lesion removed
by NdT through
aqueduct
of sylvius,
lying therefore
cranially ofb)the
tectum, theforinfratentorial
Indications
surgery andapproach
microoccipitaloccipital
transtentorial
approach.
steepangle
angle
of straight
the straight
sinus
and
theofposition
of the lesion
transtentorial
approach.Note
Note the
the steep
of
the
sinus
and
the
position
the lesion
is inappropriate as the quadrigeminal
plate obstructs the surgical exposure. Finally,
anteriorly
to the toquadrigeminal
supracerebellar
infratentorial
anteriorly
the quadrigeminalplate
plate making
making a asupracerebellar
infratentorial
approach approach
difficult. difficult.surgical approaches
the occipital transtentorial approach is preferred as well in big tumors with lateral
If a newly diagnosed pineal mass is
extension in the pulvinar thalami as it gives a better lateral exposure of the walls of
hydrocephalus or occulomotor signs are tumor. A CT is also useful to detect in- accessible by stereotactic or endoscopic
the third ventricle (6)..
generally the first clinical manifestation tratumoral calcifications or hemorrhage. biopsy and the cranial MRI is compatible
Markers:
Serum and CSF markers contribute to the diagosis of pineal parenchymal
of pineal region tumors. Hydrocephalus
tumorsisand
assessment
their malignancy.
BHCG and -foetoprotein are found in
triventricular
byof
compression
of the
germ cell
tumors.
HCG
mainly
positive
in choriocarcinomas, embryonal
aqueduct
of Sylvius
andiscan
be acute
or
chronic.
include
carcinomas
andSymptoms
mixed germ
cellheadaches,
tumors and AFP is expressed by yolk sac tumors
gait problems
and occulomotor
(high levels),
embryonic
carcinomas,signs
immature teratomas and mixed germ cell
such as Parinaud syndrome. In slow
tumors. -HCG is usually low in germinomas which are often positive for PLAP on
growing tumors, chronic hydrocephalus
immunohistochemistry
(8)..dementia. Occumay develop and cause
Biopsy:lomotor
Histological
diagnosis
is obtained
signs can also occur through
di- either by stereotactic or endoscopic
transventricular
biopsy
during open surgery. For large pineal tumors a
rect compression
of or
thedirectly
superior colliculi
Figure 2c
or thebiopsy
posterior
(6)..procedure toFigure
stereotactic
iscommisure
a safe initial
obtain2adiagnosis. For tumorsFigure 2b
Figure
2a,2a,
2b2B
andand
2c.2C.
Surgical
presentation
of of
a right
occipital
transtentorial
approach
include:
a) After
Radiology:
the
radiological
exam
of
Figure
Surgical
presentation
a
right
occipital
transtentorial
approach
include: a)
extending into the posterior part of the third
ventricule, endoscopic transventricular
dissecting the arachnoid, the tumor comes into full view. b) Resection of the tumor with dissection of
After dissecting the arachnoid, the tumor comes into full view. b) Resection of the tumor with dissection
MRI which
will reveal
biopsy choice
allowsisaccess
to tumor
tissuetheastuwell
third
ventriculostomy
the as
capsule
from
surrounding structures.toc)treat
Final view of the operative field after resection of the
of the capsule from surrounding structures. c) Final view of the operative field after resection of the
mor and its relations to adjacent ana- tumor,
under
the
corpus
callosum
the
posterior
part of the third ventricule is visible. The great vein of
hydrocephalus
(6)..
tumor,and
under
callosum
the visible.
posterior part of the third ventricule is visible. The great vein of
thethe
leftcorpus
basal vein
are also
tomical structures. Particular attention Galen
Galen and the left basal vein are also visible.
has to be given to T1+gadolinium seb) Indications
surgery
and T2
microsurgical
giant tumors of the pineal region can be removed by the combined occipital ,
quences,for
high
resolution
squences Theapproaches
supracerellar
approach
by Sekhar(10)
(Figurefirst
3).
for surrounding vessels (flow void) and transtentorial,
Even if the many
different transsinus
pineal tumor
withdescribed
a germinoma,
a biopsy should
cranial nerves, phlebo-MRI sequences types may have a preferential appearance be done in order to avoid an unnecessary
for assessing the 3D anatomy of the deep on cranial imaging, no such character- craniotomy in that case. If the radiolog3
venous system and its relation with the istics are specific for one or another tu- ical examination is compatible with an
mor type and do not preclude obtaining 4asymptomatic benign pineal cyst and
tissue for histological examination. An the serum and CSF markers are negative,
exception are benign pineal cysts which the patient can be followed up without
have a homogenous cyst content with a treatment. The treatment of other pineal
thin enhancing rim and have no or only tumors requires surgery but the choice
mild mass effect on surrounding struc- of radical or conservative resection will
tures. Except for pineal region meningio- depend on the diagnosis of the pre-surmas or falcotentorial notch meningioma gical biopsy or the intraoperative frozen
extending in the pineal region, angiogra- section. Benign tumors such as mature
phy is usually not necessary(6)..
teratomas, pineocytomas or meningioMarkers: Serum and CSF markers mas require radical surgical resection
contribute to the diagosis of pineal pa- when feasible without compromising
renchymal tumors and assessment of surrounding neurovascular structures.
their malignancy. BHCG and a-foeto- More aggressive tumors, such as maligprotein are found in germ cell tumors. nant teratomas, pinealoblastomas, emFigure 3. 3.:
GiantGiant
pineal region
meningioma
Figure
pineal
region meningioma
removed
by inco-author
using
the
b-HCG is mainly
positive
choriocar- (KD)
bryonal
carcinomas,
choroicarcinomas
removed by co-author (KD) using the combined
combined
Sekhar’s
approach
cinomas,
embryonal
carcinomas
and
and
yolk
sac
tumors
require
a combinaSekhar’s approach
mixed germ cell tumors and AFP is ex- tion of surgery, radiation therapy and
5. Results
172
MED ARH 2009; 63(3) • Revijalni članci • Reviews
The fifty-one pineal region tumors were surgically treated by senior author (NdT).
Pineal Region Tumors – Neurosurgical Review
chemotherapy. In any case
a) Pineal gland tumors
the prime goal of surgery Germinoma
Excluded
should be avoiding surgical Mature teratoma
3
morbidity even at the cost of Immature teratoma
4
a less radical surgical resecEmbryonal carcinoma
2
tion. The choice of approach
Pineocytoma
3
is a matter of evaluating the
Intermediate differentiation
1
anatomical relation of the
Pineoblastoma
2
tumor with the surrounding
Yolk sac tumor
2
structures. A steep angle of
NUMBER
17
the straight sinus makes the
11
infratentorial supracerebel- Radical resection
Subtotal
resection
2
lar approach difficult as an
4
(2
embryonal
carcinoms
and
extensive retraction of the Biopsy
2 yolk sac tumors)
cerebellum is required to
visualize and reach the pic) Complications
neal area. Moreover, in that
Number of
Reason of
case the lateral exposure of Type of complications
complication
complications
the surgical field is restricted
Occipital lobe
and renders the resection of Hemianopsia
1
retraction
larger tumors more compliOccipital
lobe
cated. Evaluating the rela- Visual seizures
1
retraction
tionship of the tumor with
1 Venous infarction
the quadrigeminal plate is Metamorphopsia
Parinaud
syndrome
quadrigeminal
also important. For smaller
1
(permanent)
plate
manipulation
midline tumors located in
IV
CN
palsy
2
Nerv
traction
the posterior part of the
Air
embolism
0
0
third ventricle and displacing the quadrigeminal plate
b) Pineal region tumors without pineal gland
and the tegmentum of the
tumors
midbrain caudally, the in4
fratentorial supracerebel- cavernous angiomas
2
lar approach is favored as PNETs
4
it allows simple, direct and Ependymomas
symmetrical exposure of the Astrocytomas grade II
5
walls of the third ventricle Hemangioblastomas
4
and internal cerebral veins Gangliogliomas
2
on both sides. In the case the Meningiomas
9
tumor lies more caudally and plexus papillomas
2
extends in the upper por- Neurocytoma
1
tion of the aqueduct of syl- Neurenteric cyst
1
vius, lying therefore cranially NUMBER
34
of the tectum, the infraten- Radical resection
29
torial approach is inappro5 (2 Astrocytomas and 3
priate as the quadrigeminal Subtotal resection
meningiomas)
plate obstructs the surgical
exposure. Finally, the occipsinus approach described by Sekhar(10)
ital transtentorial approach is preferred (Figure 3).
as well in big tumors with lateral extension in the pulvinar thalami as it gives 5. Results
The fifty-one pineal region tumors
a better lateral exposure of the walls of
were surgically treated by senior author
the third ventricle (6)..
The giant tumors of the pineal region (NdT). Only 17 of them were the neocan be removed by the combined occip- plasms originating from pineal body (piital , transtentorial, supracerellar trans- neal tumors)
6. Conclusion
Contemporary management of pineal tumors requires a multidisciplinary
cooperation where surgery represents
only one aspect of the treatment plan.
However, with the exception of germinoma where only a biopsy is needed, the
role of the surgeons still remains prominent as resection of pineal tumors requires high technical skill and experience as well as precise clinical judgment. The infratentorial supracerebellar approach and the occipital transtentorial approach when used appropriately
allow access to nearly every type of pineal neoplasms.
REFERENCES
1.
Krause F: Operative Freilegung der Vierhüge, nebst Beobachtungen bein Hirndruck un Dekompression. Zentralbl Chir.
1926;53:2812-9.
2. Stein BM: The infratentorial supracerebellar approach to pineal lesions. J Neurosurg.
1971;35:197-202.
3. Jamieson KG: Excision of pineal tumors. J
Neurosurg. 1971;35:550-3.
4. Matsuno H, Rhoton AL, Jr., Peace D: Microsurgical anatomy of the posterior fossa
cisterns. Neurosurgery. 1988;23:58-80.
5. Ono M, Rhoton AL, Jr., Peace D, Rodriguez
RJ: Microsurgical anatomy of the deep venous system of the brain. Neurosurgery.
1984;15:621-57.
6. Sawamura Y, de Tribolet N: Neurosurgical management of pineal tumours. Adv
Tech Stand Neurosurg. 2002;27:217-44.
7. Bruce JN, Stein BM: Surgical management
of pineal region tumors. Acta Neurochir
(Wien). 1995;134:130-5.
8. Sawamura Y: Overview for management. Intracranial germ cell tumors, in
Sawamura YS, H. de Tribolet, N (ed). Intracranial germ cell tumors. Wien, New
York, Springer, 1998:169-91.
9. Sawamura Y, de Tribolet N, Ishii N, Abe
H: Management of primary intracranial
germinomas: diagnostic surgery or radical resection? J Neurosurg. 1997;87:262-6.
10. Sekhar LN, Tzortzidis F: Approaches to the
pineal region. In: Sekhar LN, de Oliveira
E (eds). Cranial microsurgery:approaches
and techniques. Thieme New York, 1999.
Corresponding author: Kemal Dizdarevic,
MD, PhD. Clinic for neurosurgery. Clinical center
of Sarajevo University. Sarajevo, Bolnicka 25.
Tel.: 00 387 33 297 000. E-mail.: kemaldiz@bih.
net.ba
MED ARH 2009; 63(3) • Revijalni članci • Reviews
173
Management of a Comatose Patient with Multiple Intracranial Aneurysms - Lessons Learned
Management of a Comatose Patient
with Multiple Intracranial Aneurysms
- Lessons Learned
Kemal Dizdarevic1, Vino Apok2, Ibrahim Omerhodzic1, Tarik Masic3
Department of Neurosurgery, Clinical Center University of Sarajevo, Bosnia and Herzegovina1
St. George’s University of London, United Kingdom2
Clinic for Maxilofacial suregery,Clinical Center University of Sarajevo, Bosnia and Herzegovina3
Case report
SUMMARY
The perioperative management of a deeply comatose patient (Glasgow Coma Score, GCS 5) following a spontaneous subarachnoid hemorrhage is presented. Six intracranial aneurysms of the anterior circulation were
discovered at operation, contrary to angiographic findings. These were successfully clipped by the author (KD).
Postoperatively, the patient’s cerebral energy metabolism was monitored by bedside cerebral microdialysis in
real time. The ICP (volume)-targeted therapy (Lund concept) was utilised in accordance with findings of intrinsic brain biochemistry. Three-month follow-up showed excellent outcome (Glasgow Outcome Score,GOS 5).
Keywords: subarachnoid hemorrhage, multiple intracranial aneurysms, early surgery, Lund concept, cerebral
microdialysis, coma
1. Introduction
Intracranial aneurysm rupture, the
most common cause of spontaneous
subarachnoid haemorrhage (SAH) is
burdened with high mortality and morbidity. The rationale foe using early surgical clipping as a gold standard in such
cases is the prevention of delayed intracranial complications. There is doubtless benefit to the currently favoured
method–endovascular coilling (1,2).
However, this option is still not accessible for many neurosurgical patients, particularly those in developing countries.
In certain institutions, early surgical
clipping was prefered only for the good
grade patients (Hunt-Hess I, II, III). Comatose patients with neurological deficit
(Hunt-Hess IV i V) are not operated on
due to increased immediate postoperative mortality. Our experience favours
the treatment of almost all anterior circulation ruptured barry aneurysms by
early surgical clipping and postoperative
treatment according to the Lund concept
(ICP or volume-targeted therapy). The
important exception to this view would
be patients with a GCS of 3.
The Lund concept involves monitoring cerebral energy metabolism using cerebral microdialysis3-9. Orginally
devised to aid the management of traumatic brain injury, it has been shown to
be helpful in reducing overall mortality
after aneurysmal subarachnoid haemorrhage and preventing ischaemia. Early
surgery together with postoperative volume-targeted therapy allows an effective approach to complications caused
by haemorrhage.
174
Our objective is to present the outcome of a deeply comatose patient following a SAH who was found to have six
intracranial aneurysms. The importance
of strategic treatment planning (in this
case, arly surgical clipping and postoperative utilisation of Lund concept) is illustrated by this case.
Figure 2. Intraoperative illustration of multiple
aneurysms clipping
Surgery was undertaken by the author (KD) within 24h of the bleed. Intraoperatively, contrary to CT angiography, six aneurysms of the anterior circulation occurring bilaterally were discovered. These were successfully clipped
(Figure 2). Five of the aneurysms were
on the right (two on ICA, one on AChA,
A1 ACA and MCA) including the ruptured aneurysm (MCA). The remaining
2. Case report
H.Z., a 44-years-old male experienced
a spontaneous SAH (Fisher gr IV) secondary to aneurysmal rupture a day before
addmition to our Department. He was
deeply comatose (GCS 5, Hunt-Hess gr V,
WFNS gr V). The digital subtraction angiography (DSA), the conventional angiographical option, was not available due
to technical issues. CT angiography was
performed as an alternative and demonstrated three aneurysms of anterior cerebral circulation (Figure 1).
Figure 3. Craniotomy was done on both
sides. The catheter was placed in the left lateral
ventricle. A titanium clips and catheter for cerebral
microdialysis are visible intracranially.
Figure 1. Preoperative brain CT angiography
shows multiple cerebral aneurysms on the both
side.
MED ARH 2009; 63(3) • PRIKAZI SLUČAJA / CASE REPORTS
one was on the left (MCA bifurcation). A
modified right pteryonal (pre-temporal)
approach utilizing a trans-Sylvian route
was used. Following aneurysm clipping
and wound closure on the right , the head
was rotated and a left supra-orbital lateral approach was undertaken The left
MCA aneurysm was noted to be leaking
This was also successfully clipped (Figure 3 A and B).
After clipping, an intraventricular
catheter for ICP-monitoring and a microdialysis microcatheter for energy metabolism monitoring were placed.
Management of a Comatose Patient with Multiple Intracranial Aneurysms - Lessons Learned
Postoperatively, the patient was intubated, sedated and managed using the
Lund concept i. e. ICP (volume)-targeted
therapy (Figure 4.). This therapy focuses
on four crucial aims:
•• reduction of stress response and
cerebral energy metabolism,
•• reduction of capillary hydrostatic
pressure,
•• maintenance of colloid osmotic
pressure with strict control of fluid
balance
•• reduction of cerebral blood volume.
The brain energy metabolism was
monitored using cerebral microdialysis
equipment (3,4,5,6) (Figure 5). A month
postoperatively the patient was alert, extubated, communicating freely and laboratory investigation results were within
reference range.
Postoperative rehabilitation was
completed. By three-month follow-up,
his GOS was 5 and his Karnofsky score
was 90. Slight cognitive deterioration
was noted but there was no neurological deficit (Figure 6) (7,8,9).
3. Discussion
Spontaneous SAH caused by anterior circulation aneurysmal rupture is a
common reason for acute deterioration
of consciousness and development of
neurological deficit in a patient.
Poor preoperative status as an indication for early surgery is an area of controversy. Practice varies widely across the
neurosurgical word,
dependant largely
on ex per t opi nion within institution rather than
a ny internationally accepted evidence based guideline. In our experience, poor preoperative Hunt-Hess
grade alone should
not be a reason for
avoiding early surgery. This is illustrated by the case
Figure 4. The patient immediate postoperatively with bedside monitoring of
presented here.
brain
energy metabolism.
In such patients,
early microsurgery
followed by postis able to adapt the operative method apoperative ICP (volume)-targeted ther- propriately.
apy has shown good outcome at our
The author (K.D.) mainly utilizes a
centre. This is independent of preoper- supra-orbital lateral approach (10) for
ative grade.
the vast majority of aneurysms but recInsufficient diagnostic evaluation ognizes that multiple and giant aneupreoperatively (as in this case where DSA rysms are probably best clipped using
was not available) should be recognized pteryonal or pre-temporal approaches
as an additional risk factor for aneurysm (11,12,13). This patient was managed for
surgery. However, CT angiography can approximately 2 months postoperatively
and still does have a role even in complex on the neurosurgical intensive care unit
cases with multiple aneurysms. It is im- with therapy being guided by the Lund
portant though, to recognize the poten- concept.
tial for error with any imaging modality
This strategy is directed at brain volas illustrated here. The cerebrovascular ume regulation and maintaining cereneurosurgeon should be one who antici- bral perfusion pressure between 50 and
pates intraoperative findings other than 70 mmHg (3,7,8,14). Modification of this
those imaged on preoperative scans and strategy according to the findings of interstitial brain metabolites (glucose, lactate, piruvate, glutamate, glycerol) recorded by cerebral microdialysis is then
carried out. These indicators, measured
at the bedside (15,16,17,18), reflect the
level of brain ischemia in real time.
4. Conclusion
A poor grade patient with multiple aneurysms can benefit from early
surgical clipping, especially if accompanied by postoperative conservative
treatment directed at brain volume regulation based on bedside monitoring of
brain intrinsic biochemistry. Clearly,
this should ideally happen in the controlled environment of a neurosurgical
intensive care unit.
references
1.
Figure 5. The record of patient’s cerebral energy metabolism.
Molyneux A, Kerr R, Stratton I et al. International Subarachnoid Aneurysm Trial
(ISAT) of neurosurgical clipping versus
endovascular coiling in 2143 patients with
MED ARH 2009; 63(3) • PRIKAZI SLUČAJA / CASE REPORTS
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Management of a Comatose Patient with Multiple Intracranial Aneurysms - Lessons Learned
ruptured intracranial aneurysms: A randomised trial. Lancet, 2002; 360:1267-74.
2. Molyneux A, Kerr R, Yu LM et al.: International Subarachnoid Aneurysm Trial
(ISAT) of neurosurgical clipping versus
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ruptured intracranial aneurysms: A randomised comparison of effects on survival, dependency, seizures, rebleeding,
subgroups and aneurysm occlusion. Lancet, 2005;366:809-17.
3. Dizdarevic K. Cerebral microdialysis:
Brain ischaemia after neurotrauma and
aneurysmal haemorrhage. Doctoral dissertation. School of Medicine University
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5. Nordstrom CH, Reinstrup P, Xu W et al.:
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Corresponding author: Prof Kemal
Dizdarevic, MD, PhD. Department of
neurosurgery, Clinical Center University of
Sarajevo. Bolnicka 25, Sarajevo 71000, Bosnia
and Herzegovina. E-mail.: kemaldiz@bih.net.ba
Medical Informatics In A United And Healthy Europe
Medical Informatics
In A United And Healthy Europe
Authors: Klaus-Peter Adlassnig, Bernd Blobel, John Mantas and Izet Masic
IOS Pres, Amsterdam, The Netherlands, 2009, 1064 pages, Hard cover. ISBN 978-1-60750-044-5
This volume contains the proceedings of the Twentysecond International Conference on Medical Informatics
Europe MIE 2009, that will be held in Sarajevo, Bosnia
and Herzegovina, from 30 August to 2 September 2009.
The MIE 2009 is the European’s leading forum for presenting the results of current scientific work in healthinformatics processes, systems, and technologies.
Achievements in this area will be introduced to an
international audience. As a major event for science,
medicine, and technology, the conference provides a
comprehensive overview and in-depth, first hand information on new developments, advanced systems
and technologies, and current and future applications.
The MIE 2009 conference was organized by the European Federation for Medical Informatics (EFMI) in
cooperation with the Society for Medical Informatics
of Bosnia and Herzegovina (BHSMI). It follows the previous conferences in Cambridge (1978), Berlin (1979),
Toulouse (1981), Dublin (1982), Brussels (1984), Helsinki (1985), Rome (1987), Oslo (1988), Glasgow (1990),
Vienna (1991), Jerusalem (1993), Lisbon (1994), Copenhagen (1996), Porto Carras (1997), Ljubljana (1999),
Hannover (2000), Budapest (2002), Saint Malo (2003),
Geneva (2005), Maastricht (2006), and the conference
2008 in Gothenburg.
The proceedings contain 213 contributions to the
MIE 2009 conference. They cover all presentations
which are part of the scientific program of MIE 2009,
among them 150 full paper presentations, 21 student
paper presentations, 21 presentations that will be presented as posters, and 14 workshop descriptions. Furthermore, seven keynote addresses from eminent scientists coming from Europe and overseas are also included into the proceedings. The papers included were
selected by an International Scientific Programme Committee (SPC) out of 324 submissions after careful review
by three international reviewers for every single submission. The SPC chair and his two co-chairs (K.-P. Adlassnig, B. Blobel, and J. Mantas) are especially thankful to
all our reviewers whose efforts are highly estimated. As
a specific token of appreciation and to recognize their
work not only anonymously, the MIE 2009 reviewers’
names are listed in the proceedings. The – often extended – recommendations of the reviewers were incorporated in the final texts, and careful language revision
was carried out to achieve a high quality of presentation.
The scientific topics presented in the proceedings
volume at hand range from national and trans-national
eHealth roadmaps, health information and electronic
health record systems, systems interoperability and
communication standards, medical terminology and
ontology approaches, and social networks to Web, Web
2.0, and Semantic Web solutions for patients, health
personnel, and researchers. Furthermore, they include
quality assurance and usability of medical informatics
systems, specific disease management and telemedicine
systems, including a section on devices and sensors,
drug safety, clinical decision support and medical expert systems, clinical practice guidelines and protocols,
as well as privacy and security issues. Moreover, bioinformatics, biomedical modeling and simulation, medical
imaging and visualization and, last but not least, learning and education through medical informatics systems
is part of the included topic areas.
There are several trends and developments that can
be recognized by carefully examining the single contributions to the various topics.
First, interoperability and data exchange standards
become most important. Systems must and will be interconnected to each other: locally, nationally, and transnationally. Medical information and electronic health
record systems will be the first to benefit.
Second, ontologies are being developed in an increasing path. Medical data items and medical concepts
(terms) are represented, arranged, and interconnected
in standardized collections of “those that is” (=ontology)
in medicine. By doing so, not only the medical vocabulary that is used in an application but also the semantics of applied items and terms is defined.
Third, Web applications allow to share medical information and knowledge by many users – researchers,
staff, patients; close or far. Web 2.0 applications deliberately involve the user, and the Semantic Web provides even knowledge inferences over remote knowledge places and allows to develop futuristic systems.
Fourth, clinical decision support systems in all
possible manifestations are and will increasingly be
demanded by physicians and patients equally – after
patients’ medical data from the many data sources are
finally digitized and made available. They will provide
huge impact on medical workflow and patient care to
the benefit of the patient, the caring physician, and the
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177
Medical Informatics In A United And Healthy Europe
STUDIES
IN
HEALTH
TECHNOLOGY AND
INFORMATICS 150
150
Medical Informatics in a United
and Healthy Europe
This volume contains the proceedings of the Twenty-second International Conference on Medical Informatics Europe
MIE 2009, that was held in Sarajevo, Bosnia and Herzegovina, from 30 August to 2 September 2009.
The scientific topics present in this proceedings range
from national and trans-national eHealth roadmaps,
health information and electronic health record systems,
systems interoperability and communication standards,
medical terminology and ontology approaches, and social
networks to Web, Web 2.0, and Semantic Web solutions
for patients, health personnel, and researchers.
Furthermore, they include quality assurance and usability
of medical informatics systems, specific disease management and telemedicine systems, including a section on
devices and sensors, drug safety, clinical decision support
and medical expert systems, clinical practice guidelines
and protocols, as well as issues on privacy and security.
K.-P. Adlassnig et al. (Eds.)
Moreover, bioinformatics, biomedical modeling and simulation, medical imaging and visualization and, last but not
least, learning and education through medical informatics
systems are parts of the included topics.
Medical Informatics
in a United and
Healthy Europe
Proceedings of MIE 2009
Editors: Klaus-Peter Adlassnig
Bernd Blobel
John Mantas
Izet Masic
ISBN 978-1-60750-044-5
ISSN 0926-9630
financing health care bodies.
Most of the topics presented at MIE 2009 are interdisciplinary in nature and may be of interest to a variety of professionals: medical informatics, bioinformatics, and health informatics scientists, medical computing and technology specialists, public health, health inMEDICAL INFORMATICS IN A UNITED AND HEALTHY EUROPE
WELCOME TO
The XXII International Conference of the
European Federation for Medical Informatics
MIE
SARAJEVO
UNSA
University of Sarajevo
ISfTeH
International Society for
Telemedicine and eHealth
09
EuroRec
European Institute
for Health Records
European Association
of Healthcare IT
Managers
August 30th - September 2nd, 2009
EFMI
European Federation for
Medical Informatics
BHSMI
Society for Medical Informatics
of Bosnia and Herzegovina
www.mie2009.org
178
MED ARH 2009; 63(3) • PRIKAZI KNJIGA / BOOK REVIEWS
surance and health institutional administrators, physicians, nurses, and other allied health personnel, and
representatives of industry and consultancy in the various health fields.
The MIE 2009 conference gathers participants all
over the world, although mainly Europeans. This is reflected by the authors of the proceedings’ contributions; altogether 931 researchers have reported their
results in this volume (double author entries have not
been eliminated). By considering the country origin of
the authors, 38 different countries from Europe, North
and South America, Asia, Africa, and Australia can be
counted that contributed to this volume.
The great variety of scientific topics and countries
that will be present should guarantee both a highly interesting international Medical Informatics Europe MIE
2009 conference in Sarajevo in August/September and
a fruitful study of the proceedings by those interested
in Medical Informatics.
Acknowledgement. The editors are most grateful
to Andrea Rappelsberger for her careful and extensive
work in the preparation of the proceedings on hand.
We are thankful to Susanne Rom, whose many efforts
are appreciated. (Both are with the SPC Office in Vienna, Austria.) Without their help it would not have
been possible to produce such a valuable and comprehensive book.
Klaus-Peter Adlassnig, Vienna
Bernd Blobel, Regensburg
John Mantas, Athens
Izet Masic, Sarajevo
Medical Informatics In A United And Healthy Europe
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