ACOG’S NEW “BEST PRACTICE” GUIDELINES FOR PREECLAMPSIA: USING THEM TO MINIMIZE MORBIDITY & MORTALITY The University of Iowa & The Preeclampsia Foundation October 18, 2013 James N. Martin Jr., MD, jnmartin@umc.edu 62nd President ACOG 2010-2013 ACOG Presidential Initiative 2011-2012 Preeclampsia • Summarize the current state of knowledge • Develop practice guidelines and checklists for “Best Practices” • Identify the most compelling areas for research In the United States….. • PRE either alone or superimposed on preexisting hypertension presents the major risk • Maternal-fetal serious morbidity and mortality still occur, sometimes avoidable vs lessened • Optimal managementÆclose observation for signs and early findingsÆdiagnosisÆbest time for delivery • A continuing challenge: differentiate worsening chronic hypertension vs developing preeclampsia Some Problem Areas Identified…. • Failure of care providers to appreciate the multisystemic nature of PRE, sometimes the fault of rigid criteria for diagnosis • PRE is a dynamic and a progressive process • Continuing reevaluation of the patient required • PRE can first present or worsen during the puerperium ACOG Hypertension in Pregnancy Working Group 2011-2012 • • • • • • • • Jim Roberts (Chair) Phyllis August (Internist) George Bakris (Internist) RR Gaiser (Anesthesia) SA Karumanchi (Renal) M Lindheimer (Renal) Joey P Granger (Physiol) Eleni Z Tsigas (Patient) • Jim Martin (Ex Officio) • • • • • • • • • John R Barton (MFM) Ira M Bernstein (MFM) Maury L Druzin (MFM) A Jeyabalan (MFM) Donna D Johnson (MFM) Michelle Y Owens (MFM) George R Saade (MFM) Baha M Sibai (MFM) Cathy Y Spong (MFM) The ACOG HIP APPROACH…. • Working Group of experts: Obstetrics, Hypertension, Anesthesia, Consumer Advocate • Review the dataÆ develop evidence-based recommendations (Level I desired) • Assessment of evidence/implications/confidence in estimates of effect (very low, low, moderate or high) Æmake a recommendation strategy developed by the GRADE group [http://www.gradeworkinggroup.org/] • Develop the most appropriate course of action: Strong (all patients) Qualified (most patients) The “GRADE” approach Grading of Recommendations Assessment, Development and Evaluation (GRADE) •An approach used by many groups Evaluate and score evidence •Very low, low, moderate, or high quality of evidence Make and rate recommendation •Strong recommendation •Qualified recommendation Recommendations Strong: A strong recommendation is one that is so well supported that it would be the approach appropriate for virtually all patients. It could be the basis for health care policy. Qualified: A qualified recommendation is also one that would be judged as appropriate for most patients, but it might not be the optimal recommendation for some patients (whose values and preference differ, or who have a different attitude toward uncertainty in estimates of effect). When the Task Force has made a qualified recommendation, the health care provider and patient are encouraged to work together to arrive at a decision based on the values and judgment and underlying health condition of a particular patient in a particular situation. MAKING THE DIAGNOSIS • Maintain the classification scheme advanced by National Blood Pressure Education Program and ACOG in 1998: – GH – PRE – CHTN with Superimposed PRE Blood pressure criteria are same as prior recommendations • In recognition of the syndromic nature of PRE, we have eliminated the dependence of the diagnosis upon proteinuria…..and made it proteinuria OR any evidence of maternal compromise to be listed soon GESTATIONAL HYPERTENSION • Development of hypertension after 20 wks • Previously normotensive • SBP > 140 mmHg OR (not and/or) • DBP > 90 mmHg • Persistent for 4 hrs • BP returns to normal by 6 wks postpartum Mild PREECLAMPSIA • It’s never “mild” • Increased morbidity • Increased mortality • Rapid progression is possible – Early onset – Co-morbidities MILD PREECLAMPSIA: THE PROBLEM…. Preeclampsia is progressive •“Mild” preeclampsia seems to result in a false sense of security As an attempt to avoid this the Task Force recommends: •Preeclampsia without severe features (Preeclampsia) •Preeclampsia with severe features (Severe Preeclampsia) PROTEINURIA Preeclampsia is not just hypertension but a multisystemic syndrome. Proteinuria has been the traditional way to test this syndromic nature. Not all eclamptics or sick preeclamptics have proteinuria. Amount of protein does not correlate with maternal or fetal outcome. Conclusion: Use other signs of syndromic nature (other systemic findings) for diagnosis. PREECLAMPSIA • Gestational hypertensio n + new onset of any of the following: • Proteinuria – > 300 mg/day or Protein/Cr > 0.30 • • • • • • Thrombocytopenia Impaired liver function Renal insufficiency Pulmonary edema Cerebral disturbances Visual impairment (dipstick 1+) (IUGR out) PROGRESSION OF GESTATIONAL HYPERTENSION to Preeclampsia Saudan et al 32-35 weeks < 32 weeks Barton et al 32-35 weeks < 32 weeks Magee et al < 34 weeks 0 10 20 30 40 50 % of Patients that Later Develop Preeclampsia 60 Induction versus Expectant Management in Mild GHTN–Preeclampsia after 36 wk (HYPITAT randomized trial)* Induction (n=377) Expectant (n=379) 38.4 (36˚-41˚) 38.6 (36˚-41˚) GHTN 65% 66% Preeclampsia 33% 32% Proteinuria Bishop score <2 2-6 450 (300 - <5g) 600 (300- <5g) 25% 60% 22% 64% GA (wk) *Koopmans et al, Lancet 2009 HYPITAT Randomized Trial Maternal Outcome Induction n=377 Expectant n=379 RR (95% C.I.) 31% 44% 0.71 (0.59-0.86) 1% 3% • Pulmonary edema 0 1% • Abruptio 0 0 • Eclampsia 0 0 • Maternal ICU 2% 4% • Severe systolic HTN 15% 23% 0.63 (0.46-0.86) 14% 19% 0.75 (0.55-1.04) Composite adverse outcome • HELLP Cesarean delivery HYPITAT Randomized Trial Neonatal Outcome Induction (%) 6 Expectant (%) 8 • Perinatal deaths 0 0 • Apgar < 7 at 5 min 2 2 • Cord PH < 7.05 3 6 • NICU admission 3 2 0.25 0.25 Composite adverse outcome • RDS Koopmans et al, Lancet 2009 GHTN – PRE Without Severe Features Maternal & Fetal Evaluation ≥ 37 weeks’ gestation ≥ 34 weeks’ gestation • Labor, PPROM, FGR Suspected Abruptio Abnormal M/F testing No Yes Delivery Inpatient / outpatient Maternal / fetal testing Worsening M/F condition Labor / PPROM ≥ 37 weeks’ gestation HYPITAT D&D MANAGEMENT OF PREECLAMPSIA WITH SEVERE FEATURES • Term –Delivery • Remote from term –Individualize Deliver >34 Weeks ACUTE CONTROL OF SEVERE HYPERTENSION • Persistent (>15 min) SBP > 160 mmHg • Persistent DBP > 105 mmHg or • IV labetalol • bolus doses 20-40 mg (max 300/hr) • continuous IV infusion (1-2 mg/min) • IV bolus doses of hydralazine • 5, 10, 10 mg q 20 min (max 25 mg) • Oral nifedipine • 10-20 mg q 20 min (max 60 mg) ACOG CO 514 PREVENTION OF SEIZURES • Magnesium sulfate Intravenous regimen Loading dose: 4 or 6 g IV over 20 mins Maintenance: 2 g IV per hr • If convulsions recur 2 g dose of magnesium sulfate •Treat: Eclampsia, Preeclampsia (sev), HELLP MATERNAL-PERINATAL Outcome According to GA at Start of Expectant Management 97 70 60 55 52 % 40 35 36 24-246/7 25-256/7 n=25 n-26 26-266/7 n=36 PRE (Sev) <34 weeks 18 0 <23 wk n=27 23-236/7 n=20 Bombrys et al, Am J Ob Gyn 2007 FETAL DELIVERY GUIDELINESpreeclampsia w/severe features Expedited delivery (within 72 hrs) • Fetal distress by FHR tracing or BPP ≤ 4 • Amniotic fluid index < 5 cm • Ultrasound EFW < 5th percentile • Reverse umbilical artery diastolic flow • Labor / ROM • > 34 weeks’ gestation PROTEINURIA & PREECLAMPSIA Does the amount matter? • No differences in outcomes (< 5 vs ≥ 5 g) Renal function • Latency • • Similar outcomes (< 5, 5-9.99, ≥ 10 g/24h) • Delivery decision should not be based on: • Amount of proteinuria • Change in amount of proteinuria PRE < 34 wks WITH SEVERE FEATURES • Admit to L&D: ? Expectant Management ? • Corticosteroids, MgSO4 prophylaxis, antihypertensives • Ultrasound, FHR monitoring, symptoms, laboratory tests Contraindications to continued expectant management after initial 24-48hrs? Yes Delivery ******* • Eclampsia • < 230/7 wks (may individualize) • Pulmonary edema • Abnormal fetal testing • ARF/AKI, DIC • Abruptio placentae No PRE < 34 wks with SEVERE FEATURES No Contraindication Offer continued expectant management after first 24-48hrs • Inpatient only, D/C MgSO4 • Daily maternal / fetal testing, sxs, BP, labs (?biomarkers?) Deliver after Yes 48 hrs Additional complications present? • Persistent symptoms • HELLP / partial HELLP syndrome • FGR (<5th percentile) • REDF (umbilical artery) • Labor / PROM 24-32 wks No Expectant Rx Deliver @ 336/7 MAGNESIUM SULFATE DURING CESAREAN DELIVERY • Half-life of 5 hours • Discontinuing magnesium will not change drug interactions • DC’ing increases risk for seizure outside the operative suite MANAGEMENT OF HELLP SYNDROME Refer to tertiary care facility (< 35 wks) Admit to labor & delivery area IV magnesium sulfate Antihypertensives if SBP ≥ 160; or DBP ≥ 105mmHg 23 wks or ≥ 34 wks Fetal distress Maternal distress •Eclampsia •Abruptio placentae / DIC •Renal failure •Respiratory distress •Suspect liver hematoma < Yes Delivery No 23-34 wks Complete steroid course • 24-48 hours latency Management of HELLP Syndrome: MISSISSIPPI PROTOCOL Hypertension in Pregnancy January 2012 Class 1 or 2 HELLP Syndrome? (PLT <100K/uL, LDH>600 AST/ALT>70, +Schistocytes, Ind. Bili >1.2) Class 3 or Partial HELLP Syndrome? NO INITIATE IV DEXAMETHASONE 10mg IV q 12 HOURS Eclampsia? YES NO YES YES CONSIDER IV DEXAMETHASONE 10mg IV q 12 HOURS Severe Hypertension Difficult to Control, or CNS Symptoms? YES YES YES Continue Current Management without IV Dexamethasone NO NO NO Severe Epigastric Pain? End‐Organ Injury (renal, hepatic, CVS, CNS) and/or abruption‐DIC? NO HELLP SYNDROME: Best Practice • Martin JN Jr. Milestones in the quest for best management of patients with HELLP syndrome. Int J Gynaecol Obstet 2013 March22 [PMID: 23528799] • Martin JN Jr, Owens MY, Keiser SD, Parrish MF, Tam Tam KB, Brewer JM, Cushman JL, May WL. Hypertens Pregnancy [Level 2] 2012;31(1):79-90. [PMID: 21219123] Rate of Persistent Diastolic Hypertension & Proteinuria in POSTPARTUM Period % Hypertension Proteinuria 3 Days Hypertension Proteinuria 7 Days H Stepan et al., J Hum Hypert 2006 POSTPARTUM PREECLAMPSIA: Points to Consider In reviewing morbidity and mortality figures several mistakes leading to mortality were evident. •Care providers whose care resulted in bad outcomes: – did not appreciate the progressive nature of preeclampsia (“mild preeclampsia”). – Did not act in the absence of proteinuria despite other systemic signs (did not understand “syndromic”) – Postpartum preeclampsia & severe hypertension were frequently seen in these cases POSTPARTUM MANAGEMENT • BP monitored a minimum 72 hours postpartum • Repeat BP assessment 7-10 days postpartum – Office / clinic – Home health • Specific written discharge instructions – Headache – RUQ or chest pain – Vision impairment – Office and L&D telephone numbers LONG TERM MATERNAL OUTCOME • • • • • • Recurrent preeclampsia+ CHTN (4-fold*) Ischemic heart disease (2-fold*) Stroke (2-fold*) Venous thromboembolism(2-fold*) All-cause mortality (1.5-fold*) Preeclampsia is a screening test for future health + Barton, Sibai 2008 *Craici et al 2008 Primary Prevention of Preeclampsia Preeclampsia Pharmacopoeia What works? PREVENTION OF RECURRENT PREECLAMPSIA • Pre-pregnancy • Weight loss to ideal BMI • Control of glucose in diabetes • Control of BP in CHTN (diet, exercise) • Low dose aspirin in select patients (from 12 wks) • Not recommended • Vitamins C & E • Dietary salt restriction • Anti-HTN therapy to prevent preeclampsia PREDICTION OF PREECLAMPSIA? • Encouraging but not yet ready for routine clinical use, alone or in combination: – Identification of demographic factors – Biochemical analytes – Biophysical findings NO RECOMMENDATIONS