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ANESTH ANALG
1990;701814
181
Effects of Oral Caffeine on Postdural Puncture Headache
A Double-Blind, Placebo-Controlled Trial
William R. Camann,
Donald H. Lambert,
MD,
R. Scott Murray,
FFARACS,
Phillip s. Mushlin,
MD, PhD,
and
PhD, MD
C A M A " WR, MURRAY RS, MUSHLIN PS,
24 h later. Relief of PDPH measured as AVAS (initial VAS
LAMBERT DH. Effects of oral caffeine on postdural
puncture headache. A double-blind, placebo-controlled
trial. Anesth Analg 1990;70:1814.
- VAS at 4 h) was significantly better in the cafeine than
in the placebo group (P = 0.014). Six patients (30%)whose
PDPH was relieved by cafeine at 4 h had recurrence of
symptoms the following day. Our study demonstrates that
cafeine administered orally provides relief, albeit if sometimes transient, from PDPH with minimal side effects.
Forty postpartum patients with postdural puncture headache (PDPH) were randomly assigned to receive oral
caffeine (300 mg) or a placebo. lntensity of headache,
quantitated using a visual analogue pain scale (VAS),was
assessed imniediately before drug administration and 4 and
Postdural puncture headache (PDPH) is a distressing
complication of spinal anesthesia or unintentional
dural puncture during attempted epidural anesthesia. Caffeine, a cerebral vasoconstrictor, has long
been recognized as able to provide relief to patients
with PDPH (1). Only recently has this technique
enjoyed a resurgence in popularity. Intravenous caffeine, administered in combination with sodium benzoate (CSB), relieved PDPH in 85% of patients in a
double-blind, placebo-controlled study (2). In another study, the combination of intravenous CSB plus
hydration provided relief of PDPH in 80% of patients
(3). Intravenous CSB appears to be effective in treatment of PDPH. An oral caffeine preparation, although not previously evaluated, would be more
convenient and less expensive. Our study evaluated,
for the first time, the efficacy of oral caffeine for
treatment of PDPH in 40 postpartum patients.
Presented in part at the Society for Obstetric Anesthesia and
Perinatology Annual Meeting, Seattle, Washington, May 1989.
Received from the Department of Anesthesia, Brigham and
Women's Hospital, Harvard Medical School, Boston, Massachusetts. Accepted for publication September 21, 1989.
Address correspondence to Dr. Camann, Department of Anesthesia, Brigham and Women's Hospital, 75 Francis Street, Boston,
MA 02115.
01990 by the International Anesthesia Research Society
Key Words: ANESTHETIC TECHNIQUES,
sr1N.u-headache.
Methods
The protocol was approved by our hospital's Committee for the Protection of Human Subjects from
Research Risks. Written informed consent was obtained from all patients. Patients were evaluated
within 1-2 days postpartum by either the primary
anesthetist or a nurse-clinician, or both. When symptoms were consistent with a PDPH (frontal and/or
occipital discomfort worsened by upright posture and
relieved by lying supine), one of the investigators
was contacted. Upon clinical diagnosis of PDPH, the
patient was informed of the study protocol. Patients
were excluded from the study if they had preexisting
hypertension (or preeclampsia), a seizure disorder, or
intolerance to caffeine, or had consumed caffeinated
beverages within the previous 4 h. Study participants
were requested to consume neither caffeinated beverages nor analgesics during the initial 4-h study
interval. No intravenous fluids were administered,
and oral intake was ad libitum.
Severity of headache was scored on a 100-mm
visual analogue scale (VAS) with 0 = no headache
and 100 = worst headache imaginable (4). In a
randomized, double-blind fashion, subjects were
then given a capsule to consume by mouth. Capsules, prepared by our investigational pharmacy,
contained either anhydrous caffeine powder (USP 300
mg, Spectrum Chemical Mfg. Corp., Gardena, Calif.)
CAMANN ET AL.
ANESTH ANALG
182
1990;70:1814
Table 1. Patient Characteristics
Caffeine
(n = 20)
Placebo
(n = 20)
Height (an)"
Weight (kg)"
29.8 & 1.4
64.1 f 0.6
72.3 f 2.6
30.6 f 1.2
64.6 f 0.6
76.5 2 2.8
NS
NS
NS
Parity
Primiparous
Mdtiparous
5
15
6
14
NS
NS
Dural puncture
26 gauge
17 gauge
14
6
15
5
NS
NS
Delivery
Vaginal
Cesarean
6
14
8
NS
12
NS
Onset of headache (postpartum)
Day 1
Day 2
Day 3
8
11
12
NS
NS
NS
Characteristic
NS, not significant.
'Data expressed as mean
1
5
3
f SEM.
or placebo (lactose powder) and appeared identical.
Headache severity (VAS) was reassessed 4 and 24 h
after ingestion of the capsule. When headaches failed
to resolve within 4 h, patients were encouraged to
rest, to increase fluid consumption, and to take
analgesics. Epidural blood patch was explained as a
therapeutic option and utilized when those conservative means failed to relieve the headache.
Data were expressed as mean 2 SEM. Wilcoxon
rank-sum test was used to compare VAS scores
between groups. ,$ analysis was used to compare
frequency of blood patch. Student's t-test was used to
compare demographic data. P < 0.05 was considered
statistically significant.
Results
Forty postpartum patients were studied; 20 received
caffeine and 20 placebo. Groups did not differ in age,
height, weight, parity, route of delivery (vaginal vs
cesarean), size of needle involved in dural puncture
(26-gauge spinal vs 17-gauge epidural), or time from
dural puncture to onset of headache (Table 1).
Visual analogue scale scores before administration
of caffeine or placebo (To) did not differ between
groups (caffeine 69 2 3; placebo 60 f 4). Improvement in VAS at 4 h (To - T4) occurred in 18 patients
(90%)in the caffeine group vs 12 patients (60%)in the
placebo group (Figure 1). At 4 h, VAS scores were
lower in the caffeine (33 f 6) than in the placebo
(49
7) group. Moreover, the magnitude of the
*
decrease in VAS was more than 300% greater in the
caffeine than in the placebo group (36 f 6 vs 11 f 7;
P = 0.014) (Figure 2).
At 24 h, 30% of patients in the caffeine group had
higher VAS scores than at 4 h. Visual analogue scale
scores at 24 h did not differ between the two groups
(caffeine 41 2 8; placebo 34 f 10). Fewer epidural
blood patches were required in the caffeine than in
the placebo group, but the difference was not statistically significant (35% vs 55%). The patches, when
used, always relieved PDPH. There were no significant side effects of caffeine therapy. Two patients in
the study complained of mild and transient flushing
and jitteriness after receiving their capsule; one of
these had received caffeine, the other placebo.
When PDPHs resulting from 17-gauge dural punctures were compared with those resulting from 26gauge needles, no difference was found in initial pain
scores, efficacy of caffeine, or requirement for epidural blood patches.
Discussion
The present double-blind, randomized study demonstrates that a single, oral dose of caffeine (300 mg)
provides relief to patients with PDPH. Beneficial
effects of caffeine were rapid; relief occurred within
4 h after drug administration, and in 70% of patients,
the symptoms did not recur. Side effects were infrequent and mild.
The present findings are in agreement with those
from studies using intravenous caffeine. Sechzer and
Abel(2) demonstrated salutory effects of intravenous
CSB in a randomized study in 41 patients with PDPH.
A single 500-mg dose of CSB relieved the headache in
75% of patients, and a second dose, 2 h later, provided relief in an additional 10%. Thirty percent of
patients had recurrence of their headache after completion of treatment. Side effects were limited to
temporary dizziness and flushing. In a widely
quoted, but uncontrolled nonrandomized study,
Jarvis et al. (3) reported that PDPH was relieved in
80% of patients treated with intravenous CSB (500
mg) in 1L of Ringer's lactate solution, followed by an
additional liter of Ringer's lactate during the subsequent 2 h. Although the results of the study by Jarvis
et al. (3) were promising and consistent with those
reported by Sechzer and Abel (2), this nonrandomized study is confounded by the unknown effects of
acute 2-L hydration on PDPH, inasmuch as no placebo control was used.
The dose of caffeine used in our study (300 mg of
anhydrous powder) was 120% greater than the dose
ORAL CAFFEINE FOR POSTDURAL PUNCTURE HEADACHE
ANESTH ANALG
1990;70:1814
183
#OF PATIENTS
WORSE
8
BETTER
8
18
1
n4
Figure 1. Number of patients with improved VAS scores (T, < To)at 4 h.
a-
n4
-
'PI 0.06 vt. Placebo
*
30-
a-
10
-
lo.%&7
0-c
v
PLACEBO
I I
CAFFEINE
Figure 2 . Change in VAS pain score (To- T4).Values expressedas
mean ? SEM. ' P = 0.014 vs placebo.
used in the above-mentioned intravenous studies.
The CSB dose (500 mg) contains 250 mg of caffeine
plus 250 mg of sodium benzoate to enhance solubility
before parenteral use (5). As caffeine is almost completely absorbed after oral administration (with minimal first-pass effect) (6), our dosage was similar to
that used in the aforementioned studies.
Our study was limited to patients in the immediate
postpartum period. During this period caffeine elimination half-life is approximately twice as long as in
nonpregnant patients (12-18 h vs 6 h) owing to
decreased oxidative metabolism of caffeine (7). Thus,
effects of a given dose of caffeine may be more
prolonged in the peripartum period than at other
times. The clinical relevance of this pharmacokinetic
difference in treatment of PDPH remains to be determined.
An additional concern is whether caffeine ingestion by lactating women exposes the newborn to
clinically significant amounts of caffeine. Caffeine is
detectable in breast milk after ingestion of either
caffeinated beverages (coffee, tea, or cola) (8) or oral
tablets (150-300 mg) (9). Amounts of caffeine found
were quite small (0.5%-1.0%of maternal dose per
liter of milk), and no caffeine was detected in the
infant's urine. Only single doses of caffeine were
studied and the question of accumulation after multiple doses was not addressed. Thus, although it
appears safe to administer a single dose of caffeine to
lactating women with PDPH, effects of multiple
doses in this patient population are less clear.
Caffeineis available in many beverages and overthe-counter preparations (10,ll). However, the caffeine content of a specific beverage (e.g., coffee) may
vary widely (Table 2). Thus, a pharmaceutical caffeine
preparation, as used in the present study, provides a
more exact dosage of caffeine for treatment of PDPH.
The pathogenesis of PDPH is a multistep phenomenon (12). The inciting event is a dural tear and
cerebrospinal fluid leakage, which probably leads to
intrathecal hypotension. Traction on the meninges
and intracranial nerves could produce PDPH. However, a more appealing hypothesis, especially in view
of the efficacy of vasoactive drugs on PDPH, is that
intrathecal hypotension leads to dilation and distention of intracranial blood vessels (13,14). Indeed,
intracranial cerebrospinal fluid pressure that is lower
than lumbar cerebrospinal fluid pressure may result
in painful dilation of intracranial blood vessels. This
184
C A M A " ET AL.
ANESTH ANALG
1990;70181-4
Table 2. Caffeine Content of Common Substances
Substance
Caffeine content (mg)
Coffee"
Freeze-dried
Percolator
Drip grind
Tea'
Black
1-min brew
5-min brew
Green
1-min brew
5-min brew
Cocoa'
Coca-CoIab
Pepsi-Cola
Dr. Pepper
Mountain Dew
Jolt Cola
Chocolate candy bar (1.2 02)
No Doz' (Bristol-Myers)
Vivarin' (Beecham)
66
107
142
28
47
from PDPH precludes its recommendation as a definitive treatment for this syndrome. Whether long-term
relief would occur with multiple doses of caffeine in
combination with fluids, analgesics, or other vasoactive drugs remains to be determined.
The authors thank Linda Hertwig, RN, for referral of patients for
this study, John Fanikos, RPh, and Kathleen Benfell, RPh, for
preparation of the capsules, and Alyce Russo for secretarial assistance.
~~
~~
15
32
13
65
43
61
55
71
5
100
200
Data from Bunker and McWilliams (10) except Jolt Cola, from Reference
11.
"Coffee, tea, and cocoa measured as 5-02 (150 mL) cup.
bCola beverages as 12-02 can.
Ter tablet.
pressure differential is exaggerated in the upright
position, leading to more cerebral vasodilation and
worsening pain. Conversely, the pressure differential
is decreased or eliminated in the supine position,
lessening the stimulus for vasodilation and pain.
Thus, PDPH may be explained adequately by alterations in cerebral blood flow (CBF) and spinal fluid
dynamics. Caffeine may relieve PDPH because of its
ability to increase cerebral vascular resistance, decrease cerebral CBF, and decrease cerebral blood
volume (15-17). Recent work by Dodd et al. (18) in
support of this theory has indicated the ability of
intravenous caffeine to decrease global CBF in patients with PDPH. This decrease in CBF was coincident with relief of headache in all patients (n = 7).
Nevertheless, the effects of caffeine on PDPH were
transient, in that all seven of Dodd's patients had
return of headache 48 h after caffeine, three of whom
received epidural blood patches.
In conclusion, this study demonstrates that a single oral dose of caffeine (300 mg) is safe and efficacious, and merits consideration in the early treatment
of PDPH. In contrast to intravenous caffeine, therapy
with oral caffeine is more convenient and less expensive. Although a majority of patients had relief of
headaches without recurrence, some did recur after
completion of treatment. The tendency for caffeine,
as a single oral dose, to provide only temporary relief
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