6/10/2016

Preeclampsia/Eclampsia – Antepartum Intrapartum 2016 Management conference June 10, 2016 CMQCC A Tale of Two Task Forces Task Forces ACOG -HIP 2012 Grand Hyatt Hotel San Francisco, CA PAMR-PTF 2012

Maurice L. Druzin, MD I have no financial disclosures to report Professor and Vice-Chair Program Director, OBGYN Residency Program Department of and Gynecology Division of Maternal Fetal Medicine Stanford University School of Medicine

1 6/10/2016

Learning Objectives o To review the impact of hypertensive disorders of on maternal and perinatal morbidity and mortality. o To delineate the most common causes of maternal morbidity and mortality secondary to hypertensive disorders of pregnancy. Begins in the , and ends at the maternal endothelium. o To review the most current recommendations for the diagnosis and management of hypertensive disorders of pregnancy from ACOG and the California Preeclampsia Task Force (PTF) of CMQCC. It is a multisystem disorder o To outline a management algorithm to optimize care for patients with hypertensive disorders of pregnancy. o To review the clinical impact of implementation of Task Force recommendations.

Summary of the pathogenesis of preeclampsia.

Camille E. Powe et al. Circulation. 2011;123:2856-2869 Ref: Roberts JM, Pathyphysiology of ischemic , Seminars in Perinatology 38 (2014) 139-145 .

Copyright © American Heart Association, Inc. All rights reserved.

2 6/10/2016

Downton Abbey Downton Abbey

British Maternal Mortality in the Definitions Related to Maternal and 19 th and early 20 th Centuries Pregnancy – Related Mortality Table 1: Estimates of maternal mortality rates (MMR) from records of 13 English parishes in 50 year periods.  Death of a while pregnant or within 42 days of termination of pregnancy, irrespective of the duration and site of the pregnancy, from any cause related to or aggravated by the pregnancy or its management, but MMR per 1,000 100,000 not from accidental or incidental causes. live births Pregnancy-Related Death  Death of a woman while pregnant or within 42 days of termination of 1700 to 1750 10.5 1050 pregnancy, irrespective of the cause of death. 1750 to 1800 7.5 750 Maternal Mortality Ratio  Number of maternal deaths per 100,000 births 1800 to 1850 5.0 500

Ref: Alkema L, Chou D, Hogan D, Zhang 2013 22 USA S et al. The Lancet, November 12, 2015, Pages 1-13 7 California

Ref: Journal of the Royal Society of Medicine, Vol. 99, November 2006

3 6/10/2016

Maternal mortality ratios, 2015. Four Horsemen of Death

The Four Horsemen of Death in maternal mortality were:

• Puerperal pyrexia

• Hemorrhage

•

• Illegal

Ref: J R Soc Med 2008;99-559-663

Eclampsia American Journal of Obstetrics and Gynecology 1925(17) and 1933(575)

 Eclampsia is defined as NEW ONSET grand mal  Lazard EM. The intravenous use of in a woman with preeclampsia sulphate in puerperal eclampsia . Am J Obstet Gynecol 1925; 9:178-188 (USC)& 1933;26:647-56  Incidence is 1 in 1,000 deliveries in U.S.  The Eclampsia Trial Collaborative Group. Which for women with eclampsia? Lancet 1995 ;345:1455-63.  Mortality from eclampsia ranges from  Lucas MJ, Leveno KJ, Cunningham FG. A comparison of approximately 1% in the developed world, to as magnesium sulfate with for the prevention of high as 15% in the developing world eclampsia. N Engl J Med 1995 ;333:201-5.

Ghulmiyyah L, Sabai BM. Maternal Mortality from Preeclampsia/Eclampsia. Semin Perinatol 2012;36:56-59. 42

4 6/10/2016

Maternal Mortality Rate, USA, Magnesium sulfate California and United States; 1999-2013 400 per 100,000 LB 24.0 California Rate 22.0 21.0 19.3 United States Rate 16.9 WW II, antibiotics 19.9 18.0 15.5 16.6 15.1 16.9 14.6 14.0 15.0 13.1 12.7 10.9 11.6 12.0 9.9 10.0 13.3 9.9 12.1 11.7 9.2 11.8 11.1 9.0 9.8 9.7 7.4 8.9 7.3 6.0 7.7 6.2 3.0 HP 2020 Objective – 11.4 Deaths per 100,000 Live Births 0.0 Maternal Maternal Deathsper 100,000 Live Births 1999 2000 2001 2002 2003 2004 2005 2006 2007 2008 2009 2010 201 1 2012 2013 Year

SOURCE: State of California, Department of Public Health, California Birth and Death Statistical Master Files, 1999-2013. Maternal mortality for California (deaths ≤ 42 days postpartum) was calculated using ICD-10 cause of death classification (codes A34, O00-O95,O98-O99). United States data and HP2020 Objective use the same codes. U.S. maternal mortality data is published by the National Center for Health Statistics (NCHS) through 2007 only. U.S. maternal mortality rates from 2008 through -2013 were calculated using CDC Wonder Online Database, accessed at http://wonder.cdc.govon March 11, 2015. Produced by California Department of Public Health, Center for Family Health, Maternal, Child and Adolescent Health Division, March, Ref: Journal of the Royal Society of 2015. Medicine, Vol. 99, November 2006

Disparities in Maternal Mortality by Race/Ethnicity, California Residents; 1999-2013

60 White, Non-Hispanic 10 African-American, Non-Hispanic  The incidence of preeclampsia has Maternal Mortality Disparity Ratio 51.0 9 Ratio African-Americanto of

50 WhiteMaternal Mortality 45.7 46.1 8 increased by 25% in the United States 41.5 41.1 7 during the past two decades. 40 35.5 37.2 32.2 6 29.0 33.8 29.5 30 4.4 5 27.7 3.8 3.8 3.7 3.8 3.9 26.4 3.9 4 3.2 4.3 3.8 Preeclampsia is a leading cause of 20 3.1 3.0 3.0  3 12.2 12.4 10.9 11.8 10.9 11.5 10.9 10.7 maternal and perinatal morbidity and 9.5 9.5 2 10 6.9 7.1 7.0 Maternal Deaths per 100,000 Deaths per Maternal 100,000 Births Live 1 mortality , with an estimated 50,000- 0 0 60,000 preeclampsia-related deaths per 1999- 2000- 2001- 2002- 2003- 2004- 2005- 2006- 2007- 2008- 2009- 2010- 2011- 2001 2002 2003 2004 2005 2006 2007 2008 2009 2010 2011 2012 2013 Year year worldwide. SOURCE: State of California, Department of Public Health, California Birth and Death Statistical Master Files, 1999-2013. Maternal Ref: ACOG – HIP, 2013 mortality rates for California (deaths ≤ 42 days postpartum) were calculated using ICD-10 cause of death classification (codes A34, O00- O95,O98-O99). Produced by California Department of Public Health, Center for Family Health, Maternal, Child and Adolescent Health Division, March, 2015.

5 6/10/2016

Cause of U.S. Maternal Mortality  CDC Review of 14 years of coded data: 1979-1992  4024 maternal deaths Executive Summary :  790 (19.6%) from preeclampsia in Pregnancy

American College of 90% of CVA were Obstetricians and Gynecologists from hemorrhage James Martin, Jr, MD

Obstet Gynecol 2013;122:1122-31

MacKay AP, Berg CJ, Atrash HK. Obstetrics and Gynecology 2001;97:533-538

CA-PAMR Causes of Death (Top 5), 2002-2004 How Do Women Die Of Preeclampsia in CA? Grouped Cause of Death, Pregnancy-Related per CA-PAMR Committee Deaths CA-PAMR Final Cause of Death Among N (%) Preeclampsia Cases, 2002-2004 (n=25) Cardiovascular disease 29 (20) Final Cause of Death Number % Rate/100,000 Cardiomyopathy 19 (13) 1.0 64% Other cardiovascular 10 (7) Stroke 16 Hemorrhagic 14 87.5% Preeclampsia/eclampsia 25 (17) Thrombotic 2 12.5%

Obstetric hemorrhage 16 (11) Hepatic (liver) Failure 4 16.0% .25 15 (10) Cardiac Failure 2 8.0% DVT/ PE 15 (10) Hemorrhage/DIC 1 4.0% Other 45 (31) Multi-organ failure 1 TOTAL 145 4.0% ARDS 1 4.0% Pregnancy-Related Mortality Rate: 1.6 deaths /100,000 live births 23 24

6 6/10/2016

CA-PAMR Pregnancy-Related Deaths, Chance to Alter Outcome by Grouped Cause of Death; 2002-2005 (N=207)

Clinical Cause of Chance to Alter Outcome (%) Death Strong/Good Some None Total N CA – PAMR Obstetric hemorrhage 14 5 1 20 Deep vein thrombosis/ 10 9 1 20 pulmonary embolism Sepsis/infection 7 6 1 14 California Preeclampsia/eclampsia* 21(60) 14(40) 0 35 Cardiomyopathy and other 14 30 4 48 cardiovascular causes* Pregnancy Associated Mortality Review Cerebral vascular accident 3 4 9 16 2007 to 2014 0 15 3 18 Preeclampsia Task Force All other causes of death 15 15 4 34 Total (%) 84 98 23 205* January 2014 * Two deaths lacked sufficient records to make determination (one from each cause of death).

Maternal Morbidity and Mortality: Impact of Hypertension in CA-PAMR Preeclampsia Cohort, 2002-2004 About 8 Preeclampsia Related Mortalities/2007 in CA Near Misses: 380/year (ICU admissions)  Cohort of pregnancy-related deaths, N=145  25 (17%) of deaths were grouped as “Preeclampsia/Eclampsia” cause of death (20%,CDC)

 Over half of all pregnancy-related deaths had HTN 40-50x diagnoses Serious  50 (34%) had inpatient diagnosis of HTN 400-500x Morbidity:  57 (39%) had any diagnosis of HTN (inpatient, prenatal, 3400/year preexisting) (prolonged postpartum length of stay)

Source: 2007 All-California Rapid Cycle Maternal/Infant Database for CA Births: CMQCC

7 6/10/2016

Adapted from: Table 3: Estimated Odds Ratios of Severe Obstetric Complications for Delivery Hospitalizations With Hypertensive Disorders compared With Delivery Hospitalizations Without Hypertensive Disorders : The 1998-2006 Nationwide Inpatient Sample (N=36,537,061)

Estimated Odds Ratio (95% Confidence Interval) Rounded

Eclampsia/Preeclampsia Hypertension

Severe Mild Chronic Gestational Any Acute Renal Failure 35 6 10 2 11 Pulmonary 10 4 4 2 5 ARDS 12 3 4 1 4 PCD 17 3 4 1 5 DICS 15 3 2 2 5 Ventilation 11 2 3 1 4 Mortality 7 1 3 1 3 ARDS adult respiratory distress syndrome, PCD, puerperal cerebrovascular disorder, DICS, disseminated intravascular syndrome.

Ref: Kuklina et al, OBGYN Hypertension and Obstetric Morbidity, Ref: AJOG, Month 2016, In Press Vol. 113, No 6, June 2009

Factors Contributing to Pregnancy- Related Deaths, CA-PAMR 2002-2004 Contributing Factor Preeclampsia TOTAL (at least one factor probably or N (%) N (%) definitely contributed) OVERALL 25 (100%) 129 (89%) Improving Health Care Response PATIENT FACTORS 16 (64%) 104 (72%) Underlying significant medical conditions 8 (50%) 40 (39%)

to Preeclampsia: A California Delay or failure to seek care 10 (63%) 27 (26%)

Lack of understanding the importance of a 9 (56%) 16 (15%) Quality Improvement Toolkit health event HEALTHCARE PROFESSIONALS 24 (96%) 115 (79%) Delay in diagnosis 22 (92%) 62 (54%) Misdiagnosis 13 (54%) 36 (31%)

Funding for the development of this toolkit was provided by: Use of ineffective treatment 19 (79%) 48 (42%) Federal Title V block grant funding from the California Department of Public Health; Maternal, Child and Adolescent Health Division and Stanford University. Failure to refer or seek consultation 6 (25%) 26 (23%) 31 HEALTHCARE FACILITY 12 (48%) 72 (50%)

8 6/10/2016

Rocket science? OnlyOnly 44 thingsthings Brain surgery? pressure in pregnancy New onset (>20wks)–Gestational  Classification: 1)PE Preexisting (<20 wks)-Chronic HT  2)CHT  3)CHT+PE Diagnostic Acute Treatment Triggers  4)GHTN Mild 140 or 90 160 or 110 PTF Alternative  Management: 1)BP control Severe 160 or 110 (155 or 105)  2) prevention  3)Delivery- 34 wks,37wks.  4)Post partum surveillance

Diagnostic Criteria for Preeclampsia Diagnostic Criteria for Severe Preeclampsia Greater than or equal to 140 mm Hg systolic or greater than or equal to 90 mm Hg diastolic on two Even in the absence of , new-onset hypertension, MILD occasions at least 4 hours apart after 20 weeks of (irrespective of level) with the new onset of any of the following: gestation in a woman with a previously normal Platelet count less than 100,000/ml blood pressure( 160 or 110,repeat and treat 15mins) Renal Insufficiency Serum creatinine concentration greater than 1.1 AND Greater than or equal to 300 mg per 24-hour urine mg/dL or a doubling of the serum creatinine collection (or this amount extrapolated from a timed concentration in the absence of other renal disease collection) Impaired Liver Function Elevated blood concentrations of liver transaminases Proteinuria ( not present in 10%) Or to twice normal concentration

Protein/Creatinine ratio greater than or equal to 0.3* Severe persistent right upper quadrant or epigastric pain unresponsive to medication and not accounted AND Dipstick reading of 1+ (used only if other for by alternative diagnosis, or both quantitative methods not available) Greater than or equal to 160 mm Hg systolic or Cerebral or Visual Symptoms New onset headache most common greater than or equal to 110 mm Hg diastolic , SEVERE hypertension can be confirmed within a short interval (15 minutes ) to facilitate timely (Onset < 34 weeks more often severe) antihypertensive therapy(30-60 min) • Each measured in mg/dL. • Executive Summary: Hypertension in Pregnancy, American College of Obstetricians and Gynecologist, Obstet Gynecol 2013;122-1122-31. Copyright permission received

9 6/10/2016

HELLP Syndrome (> 20 wks) (GHTN) H (LDH)

Mild - BP Only - Severe EL Elevated Liver Enzymes LP Low Platelets < 100,000

No Proteinuria No End Organ Involvement Eclampsia Seizures Tonic/Clonic

The Deadly Triad ACOG Executive Summary on Hypertension In Pregnancy, Nov 2013 Severe Preeclampsia - HELLP Syndrome(20%) - Eclampsia (seizures) 1. The term “mild” preeclampsia is discouraged for clinical classification. The recommended terminology is: Associated with an increased risk of adverse outcomes a. “ preeclampsia without severe features ” (mild) such as: b. “ preeclampsia with severe features ” (severe ) 

 Renal Failure 2. Proteinuria is not a requirement to diagnose preeclampsia with new onset hypertension.  Sub-capsular Hepatic Hematoma

 Preterm Delivery 3. The total amount of proteinuria > 5g in 24 hours has been eliminated from the diagnosis of severe preeclampsia.  Fetal or Maternal Death 4. Early treatment of severe hypertension is mandatory at the  Recurrent Preeclampsia threshold levels of 160 mm Hg systolic or 110 mm Hg ACOG Practice Bulletin #33, Reaffirmed 2012; ACOG Committee Opinion #514, 2012; Tuffnell D, Jankowitcz D, Lindow S, et al. BJOG 2005;112:875-880. diastolic . (Repeat and Treat)

10 6/10/2016

Rocket science? OnlyOnly 44 thingsthings Brain surgery? Preeclampsia Mortality Rates in California and UK Cause of Death CA-PAMR (2002-04) UK CMACE (2003-05) among Preeclampsia Rate/100,000 Rate/100,000  Classification: 1)PE Cases Live Births Live Births  2)CHT Stroke 1.0 .47  3)CHT+PE Pulmonary/Respiratory .06 .00

 4)GHTN Hepatic .25 .19 OVERALL 1.6 .66 The overall mortality rate for Management: 1)BP control  preeclampsia in California  2)Seizure prevention is greater than 2 times that of the UK,  3)Delivery- 34 wks,37wks. largely due to differences in deaths caused by stroke.  4)Post partum surveillance 42

Key Clinical Pearl

Controlling blood pressure is the optimal intervention

to prevent deaths due to stroke  Acute-onset, severe hypertension , 160 systolic, OR 110 in women with preeclampsia. diastolic ,that is accurately measured using standard techniques and is persistent for 15 minutes or more is considered a . (repeat and treat)

Over the last decade, the UK has focused  First-Line Therapy – Recommendations  IV or/and QI efforts on aggressive treatment of both  Evidence available suggests that oral Nifedipine,10 mg, also may systolic and diastolic blood pressure and be considered as a first-line therapy. has demonstrated a reduction in deaths.  Treatment within 30-60 minutes. (repeat and treat)

11 6/10/2016

Rocket science? OnlyOnly 44 thingsthings Brain surgery?

 Classification: 1)PE  2)CHT  3)CHT+PE  4)GHTN

 Management: 1)BP control  2)Seizure prevention  Ref: AJOG – Month 2016 3)Delivery- 34 wks,37wks.  4)Post partum surveillance

American Journal of Obstetrics and Gynecology Seizure prevention/treatment 1925(17) and 1933(575)

 Lazard EM. The intravenous use of magnesium sulphate in puerperal eclampsia . Am J Obstet Gynecol 1925; 9:178-188 (USC)& 1933;26:647-56

 The Eclampsia Trial Collaborative Group. Which anticonvulsant for women with eclampsia? Lancet 1995 ;345:1455-63.

 Lucas MJ, Leveno KJ, Cunningham FG. A comparison of magnesium sulfate with phenytoin for the prevention of eclampsia. N Engl J Med 1995 ;333:201-5.

12 6/10/2016

Recommendations for Women Rocket science? OnlyOnly 44 thingsthings Brain surgery? Who Should Be Treated With Magnesium

Preeclampsia Severe Eclampsia without severe Preeclampsia  Classification: 1)PE features  2)CHT ACOG ** X X  3)CHT+PE NICE X X  4)GHTN SOGC X* X X CMQCC X* X X  Management: 1)BP control WHO X X X  2)Seizure prevention **ACOG Executive Summary, 2013: for preeclampsia without severe features, it is suggested that magnesium sulfate not be administered  3)Delivery- 34 wks With Severe universally for the prevention of eclampsia. 37 wks Without Severe * Should be considered: Numbers needed to treat ( NNT) = 109 for “mild” , 63  4)Post partum surveillance for “severe”

Delivery in preeclampsia/eclampsia PAMR – Preeclampsia Maternal Deaths DELIVERY CURE 2002 - 2007 at Death DELIVERY CURE N = 54 Delivery is the most important therapeutic intervention towards cure, but residual 37+ weeks N = 21 39% endothelial cell damage often persists into the post partum period (42 days) Less than 36 6/7 N = 33 61% weeks

At GA 24-34 weeks, delay delivery for fetal Less than 34 weeks N = 21(64%) 39% wellbeing. Unpublished data

13 6/10/2016

Ref: Henry C. Lee, Mihoko V. Bennett, Sarah Green, Alex J. Butwick, Maurice Druzin, Kathryn Melsop, Thanh G.N. Ton PAS poster, 2016. Ref: Henry C. Lee, Mihoko V. Bennett, Sarah Green, Alex J. Butwick, Maurice Druzin, Kathryn Melsop, Thanh G.N. Ton PAS poster, 2016. 5.0 With Severe Features 4.5 Without Severe Features 4.0

3.5 3.0 2.5 2.0

%Preeclampsia%Preeclampsia 1.5 1.0 0.5 - 2008 2009 2010 2011

Of 2,011,341 births during the study period, 38,269 women (1.9%) had preeclampsia Women with preeclampsia were significantly more likely to deliver preterm, w/o severe features and 31,834 (1.6%) had preeclampsia with severe features. especially those with severe features (figure below ). Almost 25% of women Preeclampsia w/o severe features remained stable at 1.9% across all four years, while preeclampsia with severe features increased over time (1.4% in 2008 to 1.7% in delivering at 29 to 32 weeks had preeclampsia, and 85-90% of women 2011 ). with preeclampsia at those gestational ages had severe features.

Key Clinical Pearl CONCLUSIONS

 Preeclampsia affects 3.5% of births in California and is increasing over time, primarily due to an In patients with increase in preeclampsia with severe severe preterm preeclampsia, features. the disease can rapidly progress to significant maternal morbidity  Preeclampsia, particularly with severe features , and/or mortality. contributes a substantial burden to , with greater than 20% of births at 29 to 33 week gestational age occurring in mothers with preeclampsia. Ref: Henry C. Lee, Mihoko V. Bennett, Sarah Green, Alex J. Butwick, Maurice Druzin, Kathryn Melsop, Thanh G.N. Ton PAS poster, 2016 .

14 6/10/2016

DELIVERY Rocket science? OnlyOnly 44 thingsthings Brain surgery?

 Expectant management without delivery at 24-34 weeks gestation for stable patients.   INPATIENT MANAGEMENT Classification: 1)PE  2)CHT  “Hope for the best, expect the worst”  3)CHT+PE ______ 4)GHTN  Delivery at 34 weeks for severe preeclampsia or severe gestational hypertension ______ Management: 1)BP control  2)Seizure prevention  Delivery at 37 weeks for preeclampsia without severe  features or mild gestational hypertension defined as BP<160 3)Delivery- 34 wks,37wks. or <110 Ref: Koopmans, et al, HYPITAT,  Lancet, 374 (2009), pp. 979–988 4)Post partum surveillance

Yogi Berra Delivery in preeclampsia/eclampsia

DELIVERY CURE

DELIVERY CURE

“It ain’t over till it’s over.” Delivery is the most important therapeutic intervention towards cure, but residual CMQCC/ACOG endothelial cell damage often persists into “It ain’t over till its over, 6 weeks postpartum” the post partum period .(42 days)

15 6/10/2016

Timing of Pregnancy-Related Deaths, CA-PAMR, 2002 to 2004 Eclampsia

80 Preeclampsia  Eclampsia is defined as NEW ONSET grand mal 68% 70 Deaths seizures in a woman with preeclampsia.

60 (n=25) 96% 50  Incidence is 1 in 1,000 deliveries in U.S. 40 68% (17/25) of deaths 88% Percent Preeclampsia Deaths 30 occurred within 4 days  20 Mortality from eclampsia ranges from 12% 8% 10 approximately 1% in the developed world, to as 4% 4% 4% 0% 0 high as 15% in the developing world 0 1 2 3 4 5 6+ Number of weeks between baby's birth and maternal death

Ghulmiyyah L, Sabai BM. Maternal Mortality from Preeclampsia/Eclampsia. Semin Perinatol 2012;36:56-59. 42

Eclampsia: Maternal-Perinatal Outcome In 254 Key Clinical Pearls Consecutive Cases over 12 years. Total births 87K (Incidence 1 in 330)  Early follow-up for all patients with preeclampsia/eclampsia  49 patients ( 19%) did not have proteinuria  within 3-7 days if medication was used during labor and delivery OR postpartum  58 patients ( 23%) did not have hypertension  within 7-14 days if no medication was used  73 (29%) occurred postpartum  40 cases (54%) occurred in the late postpartum  period (48hrs-4weeks), Postpartum patients presenting to the ED with hypertension, preeclampsia or eclampsia should  18 of these 40 cases (45%) were normotensive  All 18 had symptoms of headache or visual either be assessed by or admitted to an disturbance obstetrical service Ref: Sibai BM. Eclampsia VI. Maternal-perinatal outcome in 254 consecutive cases. Am J Obstet Gynecol Sep 163(3):1049-1054; discussion 1054-1065 1990.

16 6/10/2016

Preeclampsia Collaborative Implementation Areas

 Staff education and standardized BP Preeclampsia measurement Collaborative Summary  Rapid access to medications  IV treatment of BP’s ≥ 160mmHg systolic or Jan 2013 – August 2014 ≥ 110mmHg diastolic within 1 hour  Uniform policy for magnesium sulfate Lessons Learned  Early postpartum follow-up  Standardized postpartum patient educational materials

Preeclampsia Collaborative: Measurement Severe Maternal Morbidity Measure  Outcome Measures SMM  Severe Morbidity among women with Preeclampsia, Eclampsia, Preeclampsia superimposed on severe HTN  Prolonged postpartum LOS ( ≥4 days vaginal, ≥6 days cesarean)  Process Measures  Appropriate Medical Management (Timely Treatment)  Debrief  Balance  Monitor for dBP <80  FHR category change after treatment  Emergent delivery after treatment 67

17 6/10/2016

Severe Maternal Morbidity Table 3: Antihypertensive treatment and severe maternal Pre and Post Toolkit Implementation morbidity rates by increasing blood pressure severity in severely hypertensive women

Gold: Pre Collaborative Orange: 15 mo post implementation Ref: AJOG, Month 2016, In Press AJOG 2015;212:S69

Timely Treatment of BP with IV medication

Severe Hypertension

 17% of women with persistent severe hypertension were not treated with antihypertensive medication.

 The most common reason (54%) for not treating these women was that magnesium sulfate was started instead.

 Magnesium sulfate is not recommended as an antihypertensive treatment, and these findings highlight an opportunity for improvement.

 All guidelines recommend antihypertensive treatment for severe hypertension and at least 2 directly state that magnesium sulfate is not recommended as an antihypertensive agent .

Ref: AJOG, Month 2016, In Press

18 6/10/2016

Dignity Health Rate of Eclampsia Pre- and Post-Hypertension Bundle Downton Abbey 1.6

1.4 31% reduction P=0.02 1.2

1

0.8

N=162 N=55 N=32 0.6 Rate per 1000 per Births 1000 Rate 81/yr

0.4

0.2

0 2012-131 20142 Jan-Jul3 ‘15

Downton Abbey OBG Management – May 2016 – Vol. 28 No. 5

19 6/10/2016

Four Days Post-Partum

 Four days after delivery of a healthy OBG Management – 2015;27(10):46 child, a 31-year-old mother went to the emergency department (ED) reporting Medical Verdicts tightness in her chest, difficulty breathing, and swelling in her lower extremities.

Postpartum preeclampsia, mother dies:  Pulmonary embolism was ruled out and $6.9 M settlement she was discharged.

20 6/10/2016

 When she returned 3 days later, her legs were Estate’s Claim more swollen than before and her systolic blood pressure was 160 mm Hg.  The ED physicians and hospital staff were negligent in not diagnosing and treating  She was sent home again. postpartum preeclampsia.

 Four days later, she suffered a seizure at home, This led to seizures, brain damage, and in the ambulance during transport, and at the  hospital. death. Antihypertensive and antiseizure medications would have prevented her death.  She was transferred to another facility a few days later where she died a week after transfer.

Defendant’s Defense Verdict

 The actions taken were reasonable  A $6.9 million Illinois settlement was because she had no symptoms of reached. preeclampsia during pregnancy or delivery.

21 6/10/2016

Table 3: Antihypertensive treatment and severe maternal morbidity rates by increasing blood pressure severity in severely hypertensive women

Ref: AJOG, Month 2016, In Press Ref: AJOG, Month 2016, In Press

Severe Hypertension

 17% of women with persistent severe hypertension were not treated with antihypertensive medication.

 The most common reason (54%) for not treating these women was that magnesium sulfate was started instead.

 Magnesium sulfate is not recommended as an antihypertensive treatment, and these findings highlight an opportunity for improvement, as all guidelines recommend antihypertensive treatment for severe hypertension and at least 2 directly state that magnesium sulfate is not recommended as an antihypertensive agent. Ref: AJOG, Month 2016, In Press

Ref: AJOG, Month 2016, In Press

22 6/10/2016

Key Clinical Pearl

An organized tool to identify What can we do? “clinical signs ,” of high concern or triggers can aid clinicians to recognize and respond in a more timely manner to avoid delays in Make the diagnosis and act!! diagnosis and treatment.

Joint Commission 2010 Sentinel Alert ACOG October 2014 “Preventing Maternal Death” Recommendations  “All birthing facilities should develop a process for both the recognition and appropriate response in the event of a patient’s deteriorating condition with written criteria describing early warning signs and intervention strategies.”  “Develop protocols and drills for recognizing, responding and treating preeclampsia.” Sentinel Event Alert 2010, Issue 44, Jan 26, 2010

23 6/10/2016

Consequences of Mis-Cuffing

Overestimation of BP Underestimation of BP

Cuff too small (Systolic  by Cuff too large PREECLAMPSIA TOOLKIT as much as 15 mm Hg) Cuff not placed over brachial Brachial artery above heart TREATMENT artery level Cuff applied over clothing or RECOMMENDATIONS too loose Arm positioned below heart level and not supported Deflation of cuff too slow Deflation of cuff too fast

Preeclampsia Toolkit BP Treatment Recommendations

Systolic Diastolic Repeat BP and treat ≥ 160 ≥ 110 within 60 minutes (ideally ASAP)

 ≥155 ≥105-110 Alternative triggers* Acute-onset, severe hypertension , 160 systolic, OR 110 diastolic ,that is accurately measured using standard techniques and is persistent for 15 minutes or more is considered a hypertensive emergency. These recommendations apply to all forms of hypertension in pregnancy:  First-Line Therapy – Recommendations Gestational HTN - Preeclampsia - Severe Preeclampsia  IV labetalol or/and hydralazine  Evidence available suggests that oral nifedipine also may be * Based on Martin 2005: Martin J, Thigpen B, Moore R, et al. Stroke and severe preeclampsia and eclampsia: a paradigm shift focusing on systolic blood pressure. Obstet Gynecol 2005; considered as a first-line therapy. 105(2):246-254.

24 6/10/2016

Magnesium Sulfate  Primary effect is via CNS depression  Improves blood flow to CNS via small vessel vasodilation  Blood pressure after magnesium infusion:  6 gm loading then 2 gm/hr.

sBP sBP sBP dBP dBP dBP mm Hg 30 min 120 min mm Hg 30 min 120 min

Mild 145 143 141 87 79 82 Group ±10 ±13 ±14 ±10 ±9 ±9  Magnesium sulfate should not be considered a antihypertensive medication

Belfort M, Allred J, Dildy G. Magnesium sulfate decreases cerebral pressure in preeclampsia.Hypertens Pregnancy. 2008;27(4):315-27.

Process Improvement Summary

 Implementation of severe preeclampsia order sets  Educational sessions for treatment thresholds and accurate BP measurements  Stocking prefilled syringes of labetalol  Improved communication and care transition between departments  Removed barriers for IV antihypertensive medication administration  Continuation of magnesium sulfate during cesarean section  Debriefs become a part of hospital culture

25 6/10/2016

Patient Safety Bundles - Hypertension Getting The Job Done in Your Institution

 Establish tools / new recommendations  Establish champions and collaborators  Provide convincing rationale for change  Get providers to adopt the changes  Provide convincing evidence that the proposed changes in clinical care will improve outcome

 Distribute the convincing rationale and evidence http://www.safehealthcareforeverywoman.org/

For More Table 1 Information and to Download the Toolkit

 Visit our website: www.cmqcc.org  Or contact us: [email protected]

Available online at www.cmqcc.org

26 6/10/2016

Table 2 Table 2

British Maternal Mortality in the 19 th and early 20 th Centuries

Table 1: Estimates of maternal mortality rates (MMR) from records of 13 English parishes in 50 year periods.

MMR per 1000 live births

1700 to 1750 10.5

1750 to 1800 7.5

1800 to 1850 5.0

Ref: Journal of the Royal Society of Ref: Journal of the Royal Society of Medicine, Vol. 99, November 2006 Medicine, Vol. 99, November 2006

27 6/10/2016

Preeclampsia (pre-e-CLAMP-si-a) is a condition unique to Preeclampsia and related hypertensive disorders of human pregnancy. It is diagnosed by the elevation of the pregnancy impact 5-8% of all births in the United States. expectant mother’s blood pressure usually after the twentieth week of pregnancy combined with the appearance of Most women with preeclampsia will deliver a healthy baby excessive protein in her urine. and fully recover. However, some women will experience complications, several of which may be life-threatening to Important symptoms that may suggest preeclampsia are as mother and/or baby. A woman’s condition can go from a follows: mild form of preeclampsia to severe preeclampsia very  Headaches quickly.  Abdominal pain  Shortness of breath or burning behind the sternum Preeclampsia and other hypertensive disorders of  Nausea and vomiting pregnancy can be devastating diseases, made worse by  Confusion delays in diagnosis or management, seriously impacting  Heightened state of anxiety and/or visual disturbances such as or even killing both women and their babies before, during oversensitivity to light or after birth.  Blurred vision  Flashing spots or auras 109 110

What is the difference between preeclampsia, toxemia, PET and PIH? There are two forms of preeclampsia: Ages Affected •Preeclampsia-eclampsia •Preeclampsia superimposed on chronic hypertension

You may encounter other names like toxemia 0 - 2 PET (pre-eclampsia/toxemia) 3 - 5 PIH (pregnancy induced hypertension) EPH gestosis (edema, proteinuria, hypertension), but these designations 6 – 13 are all outdated terms and no longer used by medical experts. 14 - 18

The Preeclampsia Foundation also focuses on two other hypertensive 19 - 40 disorders of pregnancy, which include: 41 - 60 •Chronic hypertension (hypertension when you are not pregnant) which may 60 + not have been diagnosed before pregnancy

•Gestational hypertension, blood pressure rising after the 20th week but not accompanied by proteinuria. 111

28 6/10/2016

British Maternal Mortality in the 19 th Pregnancy-Related Mortality in California and early 2th Centuries Original Research RESULTS: Journal of the Royal Society of Medicine Among the 207 pregnancy-related deaths, the five leading causes were cardiovascular disease, preeclampsia or eclampsia, hemorrhage, venous thromboembolism, and Vol. 99 November 2006 amniotic fluid embolism. Among the leading causes of death, we identified differing patterns for race, maternal age, body mass index, timing of death, and method of  delivery. Overall, there was a good-to-strong chance to alter the outcome in 41% of It is only recently that the Church of England prayer book deaths, with the highest rates of preventability among hemorrhage (70%) and removed the service for the “churching of women who had preeclampsia (60%) deaths. Health care provider, facility, and patient contributing factors also varied by cause of death. recently given birth” which starts by giving thanks to God for: CONCLUSION: Pregnancy-related mortality should not be considered a single clinical entity. Reducing mortality requires in-depth examination of individual causes of death. The five leading “The safe deliverance and preservation from the great causes exhibit different characteristics, degrees of preventability, and contributing factors, with the greatest improvement opportunities identified for hemorrhage and preeclampsia. dangers of .” These findings provide additional support for hospital, state, and national maternal safety programs.

ORGANIZATIONS

ACOG HIP (Hypertension in Pregnancy Taskforce) American College of OBGYN Executive Summary – November 2013 What is preeclampsia? CMQCC PAMR

California Maternal Quality Care Collaborative Pregnancy Associated Mortality Review Department of Health California Department of Public Health

PTF

Pregnancy Task Force Toolkit – January 2014

29 6/10/2016

NEW ONSET AFTER 20 WEEKS UPDATE HYPERTENSION SEVERE HYPERTENSION Systolic 140 Systolic 160

OR

Diastolic 90 Diastolic 110 + Two years later Preeclampsia PROTEINURIA 300 mg/ 24 hours OR

Thrombocytopenia Preeclampsia Serum Creatinine Severe ALT, AST Pulmonary Edema

Severe Hypertension After 34 weeks

 Obstetric Intensive Care Manual 4 th edition in Hypertensive Emergencies Chapter by Dr. Sibai

 “Approximately 40% of patients diagnosed with preterm gestational hypertension will subsequently develop preeclampsia or severe gestational hypertension. In addition, these may result in fetal growth restriction and placental abruption. Those with severe gestational hypertension are at risk for adverse maternal and perinatal outcomes and should be managed like those with severe preeclampsia. If a woman with gestational hypertension receives antihypertensive Ref: therapy, she should be considered to have severe disease. Therefore, antihypertensive drugs should not be used during ambulatory management of these women.” 120

30 6/10/2016

Management of Suspected Severe Preeclampsia < 34 Weeks Gestation No contraindications to expectant management – Short Term

Initial 24-48 hours observation • Initiate antenatal corticosteroids if not previously administered • Initiate 24 hour urine monitoring as appropriate • Ongoing assessment of maternal symptoms, BP, urine output • Daily lab evaluation (minimum) for HELLP and renal function • May observe on an antepartum ward after initial evaluation

Proceed to delivery for: Antenatal corticosteroid treatment completed: • Recurrent severe hypertension despite therapy • Expectant management not contraindicated • Other contraindications to expectant • Consider ongoing in-patient expectant management management

Adapted from Sibai BM. Evaluation and management of severe preeclampsia before 34 weeks’ gestation. American Journal of Obstetrics & Gynecology, September 2011, pg. 191-198.

Expectant Management of Pregnancies

< 34 Weeks Gestation (From CMQCC Preeclampsia Toolkit, 2013)

Gestational HT Mild Preeclampsia Chronic HT Severe PE

Ref: Kuklina et al, Hypertension and Obstetric Morbidity, Vol. 113, No 6, June 2009

31 6/10/2016

Gestational HT Mild Preeclampsia Chronic HT Severe PE

Ref: Kuklina et al, Hypertension and Obstetric Morbidity, Ref: Kuklina et al, OBGYN Vol. 113, No 6, June 2009 Hypertension and Obstetric Morbidity, Vol. 113, No 6, June 2009

Williams Obstetrics, 24 th Edition

Condition Criteria Required Gestational Hypertension BP > 140/90 mm Hg after 20 weeks in previously normotensive women Preeclampsia – hypertension and: Proteinuria 300 mg/24 h, or Protein: creatinine ration > 0.3 or Dipstick 1+ persistent

or Thrombocytopenia Platelets < 100,00/uL Renal Insufficiency Creatinine > 1.1 mg/dL or doubling of Liver Involvement baseline Cerebral Symptoms Serum transaminase levels twice Pulmonary Edema normal Headache, visual disturbances, convulsions

Ref: Williams Obstetrics, 24 th Edition, Table 40-1, page 729

32 6/10/2016

Key Clinical Pearl Blood Pressure Basics Patients presenting with vague symptoms of: BP measurement is one of the most  headache  abdominal pain important basic clinical assessments that  shortness of breath we do, yet it is often one of the most  generalized swelling inaccurately performed assessments,  complaints of “I just don’t feel right” leading to delays in diagnosis and should be evaluated for atypical treatment presentations of preeclampsia or “severe features”

Sibai BM, Stella CL. Diagnosis and management of atypical preeclampsia-eclampsia. Am J Obstet Gynecol. May 2009;200(5):481 e481-487.

What if the BMI = 70 kg/m 2 ? Laboratory Evaluation of Preeclampsia

 Initial lab studies should include: CBC with platelet count AST, ALT, LDH (hemolysis) Creatinine, Bilirubin, Uric acid, Glucose

 For women with acute abdominal pain, add: Serum amylase, lipase and ammonia

33 6/10/2016

However… Key Clinical Pearl • Acute onset, persistent (lasting 15 min or more), severe systolic ( ≥160 mm Hg) or severe diastolic hypertension ( ≥ 110 mm Hg) or both in pregnant or All patients with severe postpartum women with preeclampsia/eclampsia constitutes a hypertensive emergency* and it is preeclampsia, irrespective of inadvisable to wait 4 hours for treatment. gestational age, should have an evaluation by an obstetrician as • If BP is still elevated above threshold after 15 min, soon possible. treat with antihypertensive medication within 30-60 min.

*Emergent Therapy for Acute-Onset, Severe Hypertension With Preeclampsia or Eclampsia, ACOG Committee Opinion, # 514, December 2011

ACOG Task Force Recommendations Expectant Management in Pregnancies with Severe Preeclampsia >24- < 34 Weeks Gestation Expectant management recommendations :  For women with mild gestational hypertension , (less than 160/110). With stable maternal/fetal conditions, continued OR pregnancy should be undertaken only at facilities with adequate maternal and neonatal intensive care  Preeclampsia without severe features at or resources beyond 37 0/7 weeks of gestation, delivery rather than continued observation is suggested. Administer corticosteroids for fetal lung maturity benefit

Ref: Koopmans CM, et al. Induction of labour versus expectant monitoring for gestational hypertension or mild preeclampsia after 36 weeks gestation. (HYPITAT). Lancet 2009;374:979-88 ACOG Executive Summary: Hypertension in Pregnancy. Obstet Gynecol 2013;122:1122-31

34 6/10/2016

Medication Timing Severe Hypertension After 34 weeks

22.2% within 30-60 min

63.0% within 30 mi n  Obstetric Intensive Care Manual 4 th edition in Hypertensive Emergencies Chapter by Dr. Sibai

 “Approximately 40% of patients diagnosed with preterm gestational hypertension will subsequently develop preeclampsia or severe gestational hypertension. In addition, these pregnancies may result in fetal growth restriction and placental abruption. Those with severe gestational hypertension are at risk for adverse maternal and perinatal outcomes and should be managed like those with severe preeclampsia. If a Treatment within 60 minutes woman with gestational hypertension receives antihypertensive Nov 2012 (Baseline): 39.1% therapy, she should be considered to have severe disease. Therefore, antihypertensive drugs should not be used during Dec 14 (Collaborative): 85.2% ambulatory management of these women.”

Quality Improvement Analysis revealed… Key Clinical Pearl  Despite clear triggers indicating serious  Magnesium sulfate therapy for seizure prophylaxis deterioration in the patient’s condition, HCP’s should be administered to any patients with: failed to recognize and respond in a timely manner  Severe Preeclampsia  Missed VS “triggers” occurred in 60% of the  Preeclampsia with “severe features” i.e., subjective preeclampsia deaths neurological symptoms (headache or blurry vision), abdominal pain, epigastric pain AND  Other “triggers” such as: proteinuria, H/A,  should be considered in patients with mild preeclampsia (preeclampsia without severe epigastric pain, deteriorating fetal status and features) altered mental status were not recognized as serious

35 6/10/2016

SMM Without Hemorrhage SMM With Hemorrhage

0.06 0.2

0.195 0.055

0.19 0.05 0.185

0.045 0.18

0.04 0.175 Series1 Series1

0.17 0.035

0.165 0.03 0.16

0.025 0.155

0.02 0.15 1 2 3 4 1 2 3 4

Dignity Health’s Preeclampsia Initiative (2014) Severe Maternal Morbidity Pre- and Post-Toolkit Implementation  Early detection – BP confirmation within 15-20 min 25 if BP > 160/110 mmHg  Includes all departments where obstetrical patients 20 present 34% Reduction  Treatment with IV antihypertensives – evidence- 15 based algorithm, treatment within 1 hour of BP P<0.001 confirmation 10  Magnesium Sulfate for seizure prophylaxis 48% Reduction Percent Patients of Percent  Follow-up with guidelines p=0.02 5  within 3-7 days if medication was used during labor and delivery OR postpartum  within 7-14 days if no medication was used 0  Standardized Patient Education Severe Maternal Morbidity Severe Maternal Morbidity Without Hemorrhage (n=817) AJOG 2015;212:S69.

36 6/10/2016

Ref: Henry C. Lee, Mihoko V. Bennett, Sarah Green, Alex J. Butwick, Maurice Druzin, Kathryn Melsop, Thanh G.N. Ton PAS poster, 2016. Ref: Henry C. Lee, Mihoko V. Bennett, Sarah Green, Alex J. Butwick, Maurice Druzin, Kathryn Melsop, Thanh G.N. Ton PAS poster, 2016. 5.0 With Severe Features 4.5 Without Severe Features 4.0

3.5 3.0 2.5 2.0

%Preeclampsia%Preeclampsia 1.5 1.0 0.5 - 2008 2009 2010 2011

Of 2,011,341 births during the study period, 38,269 women (1.9%) had preeclampsia Women with preeclampsia were significantly more likely to deliver preterm, w/o severe features and 31,834 (1.6%) had preeclampsia with severe features. especially those with severe features (figure below). Almost 25% of women Preeclampsia w/o severe features remained stable at 1.9% across all four years, while delivering at 29 to 32 weeks had preeclampsia, and 85-90% of women with preeclampsia with severe features increased over time (1.4% in 2008 to 1.7% in 2011). preeclampsia at those gestational ages had severe features.

CONCLUSIONS

 Preeclampsia affects 3.5% of births in California 35 and is increasing over time, primarily due to an 10 increase in preeclampsia with severe 12 17 features. 15

 Preeclampsia, particularly with severe features , contributes a substantial burden to preterm birth, with greater than 20% of births at 29 to 33 week gestational age occurring in

Ref: Kuklina et al, OBGYN Hypertension and mothers with preeclampsia. Obstetric Morbidity, Ref: Henry C. Lee, Mihoko V. Bennett, Sarah Green, Alex J. Butwick, Vol. 113, No 6, June 2009 Maurice Druzin, Kathryn Melsop, Thanh G.N. Ton PAS poster, 2016 .

37 6/10/2016

Ref: Henry C. Lee, Mihoko V. Bennett, Sarah Green, Alex J. Butwick, Maurice Druzin, Kathryn Melsop, Thanh G.N. Ton PAS poster, 2016. American Journal of Obstetrics and Gynecology

5.0 1925 With Severe Features 4.5 Without Severe Features 4.0  Lazard EM. The intravenous use of magnesium 3.5 sulphate in puerperal eclampsia . Am J Obstet 3.0 Gynecol 1925; 9:178-188 2.5 2.0 

%Preeclampsia%Preeclampsia 1.5 The Eclampsia Trial Collaborative Group. Which anticonvulsant 1.0 for women with eclampsia? Lancet 1995;345:1455-63. 0.5 -  Lucas MJ, Leveno KJ, Cunningham FG. A comparison of 2008 2009 2010 2011 magnesium sulfate with phenytoin for the prevention of eclampsia. N Engl J Med 1995;333:201-5. Of 2,011,341 births during the study period, 38,269 women (1.9%) had preeclampsia w/o severe features and 31,834 (1.6%) had preeclampsia with severe features. Preeclampsia w/o severe features remained stable at 1.9% across all four years, while preeclampsia with severe features increased over time (1.4% in 2008 to 1.7% in 2011 ).

38