preeclampsie Basel 16 handout

PREECLAMPSIAThierry Girard

1122 VOL. 122, NO. 5, NOVEMBER 2013 OBSTETRICS & GYNECOLOGY

Hypertension in PregnancyReport of the American College of Obstetricians and Gynecologists’ Task Force on Hypertension in Pregnancy

Executive Summary

T he American College of Obstetricians and Gyne-cologists (the College) convened a task force of experts in the management of hypertension in pregnancy to review available data and publish

evidence-based recommendations for clinical practice. The Task Force on Hypertension in Pregnancy comprised 17

-utive summary includes a synopsis of the content and task force recommendations of each chapter in the report and is

Hypertensive disorders of pregnancy remain a major health issue for women and their infants in the United

-

women for signs of preeclampsia and then delivery to termi-

-tality still occur. Some of these adverse outcomes are avoid-

some of the problems that face neonates are related directly -

turity that results from the appropriate induced delivery of the fetuses of women who are ill. Optimal management

-

optimal time for both maternal and fetal well-being. More recent clinical evidence to guide this timing is now avail-

able. Chronic hypertension is associated with fetal morbid-ity in the form of growth restriction and maternal morbidity manifested as severely increased blood pressure (BP). How-

with the superimposition of preeclampsia. One of the major challenges in the care of women with chronic hypertension is deciphering whether chronic hypertension has worsened

task force provides suggestions for the recognition and man-agement of this challenging condition.

in the understanding of preeclampsia as well as increased

there remain areas on which evidence is scant. The evidence is now clear that preeclampsia is associated with later-life

needed to determine how best to use this information to

management of preeclampsia that warrant special atten--

ate the multisystemic nature of preeclampsia. This is in part

diagnosis such as “mild preeclampsia” (which is discour-aged) applies only at the moment the diagnosis is estab-

-dates frequent reevaluation for severe features that indi-cate the actions outlined in the recommendations (which are listed after the chapter summaries). It has been known

Hypertension in Pregnancy

-

Task Force on Hypertension in Pregnancy. 2013. pp. 1122–31.

SPECIAL ARTICLE

What’s new in obstetric anesthesia? Focus on preeclampsia

L.R. LeffertDepartment of Anesthesia, Critical Care & Pain Medicine, Massachusetts General Hospital, Boston, MA,USA

ABSTRACTRecent advances in the diagnosis, pathogenesis, and understanding of preeclampsia-related morbidity provide opportunities tooptimize clinical management of the mother and fetus. These discoveries are timely, as contemporary data suggest that theprevalence of preeclampsia, affecting 7.5% of pregnancies globally and 2–5% in the USA, has increased by up to 30% over thelast decade. Managing pregnant patients with preeclampsia can be challenging for all members of the obstetric care team dueto the disease’s multi-organ system maternal and fetal effects. This review presents recent updates in the definition of preeclampsia,etiology, comorbidities and therapeutic interventions and discusses how they impact the care of these high-risk patients.

!c 2015 Elsevier Ltd. All rights reserved.

Introduction

Recent advances in the diagnosis, pathogenesis, andunderstanding of preeclampsia-related morbidity pro-vide opportunities to optimize clinical management ofthe mother and fetus. These discoveries are timely, ascontemporary data suggest that the prevalence ofpreeclampsia, affecting 7.5% of pregnancies globally1

and 2–5% in the USA, has increased by up to 30% overthe last decade.2 The overall morbidity and mortalityassociated with preeclampsia remains high (odds ratio(aOR) for death 6.9; 95% confidence interval (CI) 5.2–9.2 in severe preeclamptic vs. normotensive women).3

Up to an estimated 60% of these deaths are potentiallyavoidable.4

Managing pregnant patients with preeclampsia canbe challenging for all members of the obstetric care teamdue to the disease’s multi-organ system maternal andfetal effects. This review presents recent updates in thedefinition of preeclampsia, etiology, comorbidities andtherapeutic interventions and discusses how they impactthe care of these high-risk patients.

Update on the preeclampsia guidelines

In the past four years, the World Health Organization(WHO), the Society of Obstetricians andGynaecologists of Canada (SOGC), the AmericanCongress of Obstetricians and Gynecologists (ACOG),and the UK National Institute for Health and CareExcellence (NICE) have each updated its preeclampsiaguidelines to promote more timely diagnosis and man-agement (Table 1).5–8 The American Congress ofObstetricians and Gynecologists’ Task Force Reporton Hypertension in Pregnancy highlights that quantify-ing urine protein levels delays the diagnosis and treat-ment of preeclampsia. This observation has promptedrevision of the 2002 definition of preeclampsia to includehypertension with ‘‘severe features’’, such as headacheor renal dysfunction, without proteinuria (Fig. 1). Toemphasize that patients without severe features canquickly progress to signs or symptoms of end-organ dys-function, ACOG replaced ‘‘mild’’ preeclampsia with‘‘preeclampsia in the absence of severe features’’.7

Both the UK and Canada now advocate treating moder-ate (systolic blood pressure (SBP) 150–159 mmHg ordiastolic blood pressure (DBP) 100–109 mmHg) as wellas severe (SBP P160 mmHg or DBP P110 mmHg)maternal hypertension. They and the USA also targetthe postpartum period as a particularly vulnerable timefor hypertension-related complications.

There is increasing recognition that distinguishingbetween early-onset preeclampsia (typically defined as<34 weeks’ gestational age) and late onset (P34 weeks’gestational age) can help identify women more likely

Accepted March 2015

The 2015 Sam Hughes Lecture presented at the Society for ObstetricAnesthesia and Perinatology Sol Shnider Obstetric Anesthesia Meet-ing, San Francisco, CA, USA, March 2015.Correspondence to: Lisa R. Leffert, Chair Obstetric AnesthesiaDivision, Department of Anesthesia, Critical Care & Pain Medicine,Massachusetts General Hospital, 55 Fruit Street, Boston, MA 02114,USA.E-mail address: [email protected]

International Journal of Obstetric Anesthesia (2015) 24, 264–2710959-289X/$ - see front matter !c 2015 Elsevier Ltd. All rights reserved.http://dx.doi.org/10.1016/j.ijoa.2015.03.008

www.obstetanesthesia.com

Copyright © 2015 International Anesthesia Research Society. Unauthorized reproduction of this article is prohibited.XXX 2015 Volume XXX Number XXX www.anesthesia-analgesia.org 1

Copyright © 2015 International Anesthesia Research SocietyDOI: 10.1213/ANE.0000000000000686

The aim of this review is to synthesize key concepts and novel research from the published literature in obstetric anesthesia, obstetric practice, and maternal

and perinatal health for the calendar year 2013. These top-ics were recently addressed in the “What’s New in Obstetric Anesthesia” lecture presented at the 46th Annual Society of Obstetric Anesthesia & Perinatology Meeting in Toronto, Ontario, Canada. This lectureship, which began in 1975, was renamed in 1995 in honor of Dr. Gerald Ostheimer, a mas-ter clinician and researcher in the field. Articles were cho-sen based on their potential to impact future practice and investigation, to highlight obstetric anesthesiologists’ role as peridelivery physicians, and to improve multidisciplinary coordination of care. The review begins with an assessment of the major threats to maternal and fetal safety and well-being, and the anesthesiologist’s role in mitigating them. Current concepts in labor analgesia and intra- and postopera-tive cesarean delivery anesthesia/analgesia are explored. An annotated bibliography is included as Supplemental Digital Content (http://links.lww.com/AA/B86).

MATERNAL OUTCOMESHistorically, the U.K. Centre for Maternal and Child Enquiries provided in-depth analyses of maternal deaths from nationally maintained, clinically detailed databases. Using similar methodology, in 2013 a multidisciplinary group of perinatal experts published their analysis of 660 maternal deaths in France, occurring between the years 1998 and 2007.1 Despite an increase in risk factors, such as advanced maternal age, obesity, and cesarean delivery, the reported maternal mortality ratio was stable over the time period, at 8 per 100,000 live births. The “direct” (i.e., pregnancy-related) causes of death were similar to those in the United Kingdom and United States and included hemorrhage (18%), hypertensive disorders of pregnancy (10%), amniotic fluid embolus and thromboembolism (each 10%–12%), early pregnancy death (5.1%), and sepsis (3.0%). Anesthesia-related deaths accounted for 1.8% of the “direct” deaths. Cardiovascular disease was the primary “indirect” cause of maternal death. Over half of the maternal deaths were judged to be potentially avoidable, often due to delay in or inadequate care delivered by obstetric and anesthesia

providers. This deficiency was previously reported in sev-eral other high-income countries.2–6

In the United States, investigation of severe maternal mor-bidity and mortality is increasingly accomplished through analyses of large administrative datasets, particularly in the case of rare events.7,8 Using the Medicaid Analytic eXtract dataset (years 2000 to 2007) and a cross validation technique, Bateman et al.9 devised a simple measure to summarize the burden of illness in the obstetric population. This obstetric risk score, which performed better in the obstetric population than previously developed non-obstetric indices, has applications in epidemiologic, health services and comparative effective-ness research. The odds of maternal end-organ injury or death increased for each point increase in the comorbidity risk score (odds ratio [OR], 1.37; 95% confidence interval [CI], 1.35–1.39).

Obstetric HemorrhageObstetric hemorrhage is the primary cause of maternal death worldwide. A 2013 retrospective review of the Nationwide Inpatient Sample, the largest U.S. inpatient health care utilization dataset representing approximately 20% of all delivery admissions, reported a doubling of the postpartum hemorrhage (PPH) rate (from 1.9 per 1000 deliveries in 1999 to 4.2 per 1000 deliveries in 2008, P value for yearly trend < 0. 0001), with increases in both severe atonic and nonatonic hemorrhage.10 Many of the expected risk factors were pres-ent in the affected patients, including advanced maternal age (adjusted OR [aOR], 1.5; 95% CI, 1.5–1.6), multiple preg-nancy (aOR, 2.8; 95% CI, 2.6–3.0), uterine fibroids (aOR, 2.0; 95% CI, 1.8–2.2), preeclampsia (aOR, 3.1; 95% CI, 2.9–3.3), chorioamnionitis (aOR, 2.9; 95% CI, 2.5–3.4), placenta previa or abruption (aOR, 7.0; 95% CI, 6.6–7.3), cervical laceration (aOR, 94.0; 95% CI, 87.3–101.2), uterine rupture (aOR, 11.6; 95% CI, 9.7–13.8), instrumented vaginal delivery (aOR, 1.5; 95% CI, 1.4–1.6), and cesarean delivery (aOR, 1.4; 95% CI, 1.3–1.5). However, changes in these risk factors explained only 5.6% of the PPH increase. This administrative dataset lacked the clinical detail necessary to explore other poten-tially relevant changes in maternal status (e.g., obesity) and obstetric practice (e.g., induction or augmentation of labor).

To address the hazards of PPH, obstetric hemorrhage treat-ment protocols have been developed by multidisciplinary teams around the world. The “New WHO Recommendations on Prevention and Treatment of Postpartum Hemorrhage” were released, outlining the strategic approach in low-income countries.11 Uterotonic drugs, ideally oxytocin, should be used during the third stage of labor, and for intractable PPH. Temporizing measures, including bimanual uterine compres-sion, nonpneumatic antishock garments, and external aortic compression, are indicated until further care is available.11 The European Society of Anaesthesiology’s expert “Guidelines for the Management of Severe Perioperative Bleeding” in obstetric hemorrhage emphasizess the importance of initiat-ing uterotonic therapy, but progressing to mechanical uterine preservation maneuvers (i.e., B-Lynch or compression sutures

What’s New in Obstetric Anesthesia: The 2014 Gerard W. Ostheimer LectureLisa Leffert, MD

From the Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, Boston, Massachusetts.Accepted for publication October 30, 2014.Funding: Supported by departmental funds.The author declares no conflicts of interest.Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal’s website (www.anesthesia-analgesia.org).Reprints will not be available from the author.Address correspondence to Lisa Leffert, MD, Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, 55 Fruit St., Boston, MA 02114. Address e-mail to [email protected].

SPECIAL ARTICLEE

Int J Obstet Anesth. 2015;24(3):264–71.

Anesth Analg. 2015;120(5):1065–73.

twice within 4 hours, >20 weeks

≥ 140 mmHg

≥ 90 mmHg

preeklampsia

proteinuria > 300 mg/24h

160

100

severe

bestätigt innerhalb von Minuten

≥160 mmHg / ≥ 100 mmHg

Platelets < 100’000/µl

Kreatinine > 100 mmol/l (1.1 mg/dl)

ASAT/ALAT doubled

Pulmonary edema

cerebral or visual symptoms

≥ 140 mmHg≥ 90 mmHg

preeclampsiasevere

proteinuria > 300 mg/24h

1124 Executive Summary: Hypertension in Pregnancy OBSTETRICS & GYNECOLOGY

BOX E-1. Severe Features of Preeclampsia (Any of these findings)

-

ready for clinical use.

TASK FORCE RECOMMENDATION

appropriate medical history to evaluate for risk factors is not recommended.

Quality of evidence: Moderate Strength of recommendation: Strong

Prevention of Preeclampsia

adverse outcomes from preeclampsia in unselected women at high risk or low risk of preeclampsia. Calcium may be useful to reduce the severity of preeclampsia in populations

United States. The administration of low-dose aspirin (60–80 mg) to prevent preeclampsia has been examined in

relevant to low-risk women but may be relevant to popula-tions at very high risk in whom the number to treat to achieve the desired outcome will be substantially less. There is no evidence that bed rest or salt restriction reduces preec-lampsia risk.

TASK FORCE RECOMMENDATIONS

-

gestation or preeclampsia in more than one prior preg-

suggested.*

Quality of evidence: ModerateStrength of recommendation:

of aspirin to prevent preeclampsia indicates a small reduction in the incidence and morbidity of preeclampsia and reveals no

be excluded. The number of women to treat to have a thera-

preeclampsia is not recommended.

Quality of evidence: High Strength of recommendation: Strong

ing pregnancy for the prevention of preeclampsia.

Quality of evidence: Strength of recommendation:

physical activity not be used for the primary prevention of preeclampsia and its complications.

Quality of evidence: Strength of recommendation:

Management of Preeclampsia and HELLP SyndromeClinical trials have provided an evidence base to guide man-

Task Force on Hypertension in Pregnancy. 2013. pp. 1122–31.

proteinuria optional !

PREECLAMPSIA

• 5-8 % of pregnancies

• Early (severe): <32 weeks gestation

• Risk factors (selection)• Diabetes• Primipara > 40 years• Obesity• Multiples• Hypertension

Edema

HELLP

• Hemolysis

• Elevated Liver enzymes

• Low platelets

MECHANISM

• unclear

• immunological

• discrepancy of thromboxane/prostacycline

• prophylaxis with ASS

Gynäkologe 2013 · 46:193–198DOI 10.1007/s00129-013-3140-zOnline publiziert: 10. März 2013© Springer-Verlag Berlin Heidelberg 2013

H. Schneider · M. BaumannUniversitätsklinik für Frauenheilkunde, Inselspital Bern, Schweiz

Präeklampsie, Pathogenese und Vorhersage

Weltweit treten 8,5 Mio. Fälle von Prä- eklampsie auf [33]. Die Prävalenz ist re-gional unterschiedlich, sie liegt zwischen 2 und 8% [27, 32]. In den industrialisier-ten Ländern ist die Prävalenz geringer als in den Entwicklungsländern. In der Schweiz beträgt sie 2,3% [5]. Die Präek-lampsie ist mit 100.000 Todesfällen pro Jahr eine der führenden Ursachen der Müttersterblichkeit. Neben einer hohen perinatalen Mortalität ist sie für 15% al-ler Frühgeburten und 28% der intraute-rinen Wachstumsrestriktionen (IUGR) verantwortlich [18, 28]. Darüber hinaus ist die Präeklampsie mit Langzeitmor-bidität von Mutter und Kind assoziiert [6]. Die eigentlichen Ursachen der Prä-eklampsie und der Eklampsie sind noch nicht geklärt, und die einzige Therapie ist die Beendigung der Schwangerschaft.

Eine frühzeitige Vorhersage dieser Schwangerschaftskomplikation eröff-net Möglichkeiten zur Beeinflussung des Schwangerschaftsausganges, wie die Zu-weisung an ein Zentrum für perinatale Medizin, eine umfassende Schwanger-schaftsvorsorge und die Entbindung zu einem Zeitpunkt, der ein möglichst güns-tiges Ergebnis verspricht. Der Erfolg einer medikamentösen Prophylaxe hängt von der Wahl einer geeigneten Substanz und von einem frühzeitigen Beginn der Ein-nahme ab.

Durch die negative Vorhersage bei Schwangeren mit anamnestischer Belas-tung in vorausgegangenen Schwanger-schaften werden unnötige Hospitalisie-rung sowie aufwendige ambulante Über-

wachungsmaßnahmen vermieden, sodass neben Kosten der Schwangeren und ihren Angehörigen auch psychosoziale Belas-tungen erspart bleiben.

Pathogenese

Die definitive Behandlung einer Präek-lampsie setzt die Entfernung der Plazenta im Rahmen einer Schwangerschaftsbeen-digung voraus, was auf die zentrale Be-deutung der Plazenta für die Entstehung einer Präeklampsie schließen lässt. Als wichtigstes Element der Plazenta ist ein intakter Trophoblast zentrale Vorrausset-zung für eine ungestörte Schwangerschaft. Störungen bei der Entwicklung des Tro-phoblasten können zu Schwangerschafts-pathologien führen. In Abhängigkeit von der Art der Störung sowie von Zeitpunkt der Einwirkung können eine Präeklamp-sie, eine intrauterine Wachstumsrest-riktion oder eine Kombination der bei-den Pathologien entstehen. Im Extrem-fall kann eine Trophoblastpathologie zu einem frühen Schwangerschaftsverlust führen [15].

Umwandlung der Spiralarterien

Lange konzentrierte sich die Erforschung der Pathogenese der Präeklampsie auf die physiologische Umwandlung der Spiral-arterien und deren Störungen. Bei einer normalen Schwangerschaft kommt es als Folge einer Invasion von Trohoblastzellen in die Dezidua und die Endabschnitte der Spiralarterien zu deren Umwandlung in

weite Schläuche, die damit ihre Elastizität und jegliche vasomotorische Regulierbar-keit verlieren [8].

Diese Veränderungen der Gefäße füh-ren zu einer deutlichen Verlangsamung der Strömungsgeschwindigkeit, mit der das mütterliche Blut in den intervillösen Raum der Plazenta eintritt (. Abb. 1a). Bei der Präeklampsie bleibt die physio-logische Umwandlung der Spiralarterien unvollständig, und das mütterliche Blut strömt mit unverminderter Geschwin-digkeit in den intervillösen Raum ein (. Abb. 1b, [8]).

» Bei der Präeklampsie bleibt die Umwandlung der Spiralarterien unvollständig

Neben der Umwandlung der Spiralar-terien ist die Angiogenese ein zentraler Vorgang in der Entwicklung der Plazenta. Die proangiogenetischen Faktoren PLGF (Plazentawachstumsfaktor) und VEGF („vascular endothelial growth factor“) binden an Fms-like Tyrosinkinase 1 ( Flt-1, auch VEGF-Rezeptor genannt) in der Trophoblastmembran und stimulieren die Angiogenese. PLGF, VEGF und Flt-1 werden in Trophoblastzellen synthetisiert. Hypoxie und oxidativer Stress bewirken

Gynäkologie aktuell

Basierend auf einem Vortrag, gehalten von H. Schneider aus Anlass der Verleihung der Ehrenmitgliedschaft der Polnischen Gesellschaft für Gynäkologie, Kattowitz, 20. September 2012.

RedaktionW. Janni, UlmR. Kimmig, EssenN. Maass, Aachen

193Der Gynäkologe 3 · 2013 |

Gynäkologe; 2013 6;46(3):193–8.

Cardiovascular Management in Pregnancy

703

Preeclampsia is a pregnancy-specific multi-organ syn-drome that affects 2% to 8% of pregnancy.1 It is a unique

condition of placental pathogenesis with acute onset of predominantly cardiovascular manifestations attributable to generalized vascular endothelial activation and vaso-spasm resulting in hypertension and multi-organ hypoper-fusion.2,3 The major scientific societies provide different criteria for the diagnosis of preeclampsia. Common to all diagnostic criteria is that preeclampsia is a syndrome char-acterized by new-onset hypertension (≥140 mm Hg systolic blood pressure [SBP] or ≥90 mm Hg diastolic blood pres-sure [DBP]) arising after 20 weeks of gestation with ≥1 organ system involvement2–7 and complete resolution within 12 weeks postpartum2–5 (Table 1). The terms “preterm” or “early-onset” preeclampsia are used to try and delineate the severity of the disease in relation to the need for iatrogenic delivery before 37 weeks (preterm preeclampsia)8 or the time of the diagnosis at or before 34 weeks of gestational age (early-onset preeclampsia),6,7 respectively. Although not distinct entities, it is increasingly becoming apparent that early-onset or preterm preeclampsia is especially associ-ated with poor placentation,9 fetal growth restriction, and worse long-term maternal cardiovascular outcomes than late-onset preeclampsia, whose pathogenesis is more related to predisposing cardiovascular or metabolic risks for endo-thelial dysfunction.10 Furthermore, because the pathogenesis of preeclampsia has not been fully elucidated, the search for predictive markers and a preventative strategy remains an unfulfilled goal. Hence, clinical management is mainly symptomatic and directed to prevent maternal morbidity and mortality.2–4 Preeclampsia is 1 of the leading causes of maternal morbidity and mortality worldwide, and delay in the treatment of severe hypertension and diagnosis of pre-eclampsia complications contribute significantly to maternal mortality.11 Mortality rates have been shown to be reduced in countries such as the United States and the United Kingdom after the introduction of detailed national guidelines for the management and with increased awareness of the impor-tance of reduction of severely raised blood pressure (BP).12,13

There is scant and conflicting information about the impact on the heart.2 Previous studies on the cardiovascular changes in preeclampsia provided contradictory results mainly attribut-able to limitations in technology, patient selection, and data

interpretation.14 More recent studies have outlined better the cardiovascular profile in preeclampsia from the preclinical phase of the disease to the postpartum period and the cardio-vascular and cardiopulmonary complications associated with this condition.14 Multiple exceptional and exclusive changes in cardiac structure and function have been described in pre-eclampsia, suggesting that these women display abnormal cardiac adaptation to pregnancy.14 These cardiac changes may be fundamental in explaining these women’s increased pre-disposition toward preeclampsia and long-term postpartum cardiovascular disease (CVD). Indeed, the development of pre-eclampsia is now considered a risk factor for long-term CVD.15 This review focuses on this recent evidence and its implication for the cardiovascular management of preeclampsia.

Preeclampsia and the Cardiovascular SystemThe Cardiovascular Changes in the Preclinical Phase of PreeclampsiaIn the preclinical phase of preeclampsia, vascular reactivity, hemodynamic indices, and left ventricular (LV) properties are subtly impaired, especially in those women destined to develop preterm preeclampsia (Level 2 evidence).16–26 At midgestation, there is a shift toward a low cardiac index associated with a high total vascular resistance index, increased mean arterial pressure, contracted intravascular volume, and reduced venous reserve capacity (Level 2).16–26 In contrast, the hemodynamic profile of women destined to develop late-onset preeclampsia is not well delineated, with some authors reporting a normal cardiac index and increased total vascular resistance index at midgestation,22 and others reporting a high cardiac output/low TVR status.17,18,23 However, the latter authors did not nor-malize hemodynamic measures for body surface area or body mass index, notwithstanding the significant differences in the anthropometric parameters in the analyzed study groups. Women destined to develop preterm or term preeclampsia also show abnormal LV remodeling patterns, usually LV concentric remodeling and concentric hypertrophy.22,23 Women destined to develop preterm preeclampsia also show evidence of LV mild diastolic dysfunction (30%) and segmental impaired myocar-dial relaxation (70%).22 This diastolic impairment is associated with increased afterload and adverse LV remodeling as demon-strated by significantly higher mean arterial pressure, total vas-cular resistance index, relative wall thickness, and LV concentric

Cardiovascular Implications in PreeclampsiaAn Overview

Karen Melchiorre, MD, PhD; Rajan Sharma, MD, MRCP; Basky Thilaganathan, MD, PhD, FRCOG

(Circulation. 2014;130:703-714.)© 2014 American Heart Association, Inc.

Circulation is available at http://circ.ahajournals.org DOI: 10.1161/CIRCULATIONAHA.113.003664

From the Department of Obstetrics and Gynecology, Santo Spirito Hospital, Pescara, Italy (K.M.); and Department of Cardiology and Cardiothoracic Surgery (R.S.) and Fetal-Maternal Medicine Unit, Department of Obstetrics and Gynecology (B.T.), St. George’s University of London, London, UK.

Correspondence to Basky Thilaganathan, MD, PhD, FRCOG, Fetal Medicine Unit, 4th Floor, Lanesborough Wing, St. George’s University of London, London SW17 0RE, UK. E-mail: [email protected]

by guest on September 9, 2015http://circ.ahajournals.org/Downloaded from

Circulation. 2014;130(8):703–14.

myocardial infarction 13

congestive heart failure 8

cerebral ischemia 14

TREATMENT

Original Research

Pregnancy-Related Mortality in CaliforniaCauses, Characteristics, and Improvement Opportunities

Elliott K. Main, MD, Christy L. McCain, MPH, Christine H. Morton, PhD, Susan Holtby, MPH,and Elizabeth S. Lawton, MHS

OBJECTIVE: To compare specific maternal and clinicalcharacteristics and contributing factors among the fiveleading causes of pregnancy-related mortality to developfocused clinical and public health prevention programs.

METHODS: California pregnancy-related deaths from2002–2005 were identified with enhanced surveillanceusing linked birth and death certificates. A multidisciplin-ary committee reviewed medical records, autopsy re-ports, and coroner reports to determine cause ofdeath, clinical and demographic characteristics, chanceto alter outcome, contributing factors (at health care pro-vider, facility, and patient levels), and quality improve-ment opportunities. The five leading causes of deathwere compared with each other and with the overallCalifornia birth population.

RESULTS: Among the 207 pregnancy-related deaths, thefive leading causes were cardiovascular disease, preeclamp-sia or eclampsia, hemorrhage, venous thromboembolism,and amniotic fluid embolism. Among the leading causes ofdeath, we identified differing patterns for race, maternalage, body mass index, timing of death, and method ofdelivery. Overall, there was a good-to-strong chance to

alter the outcome in 41% of deaths, with the highest ratesof preventability among hemorrhage (70%) and preeclamp-sia (60%) deaths. Health care provider, facility, and patientcontributing factors also varied by cause of death.

CONCLUSION: Pregnancy-related mortality should notbe considered a single clinical entity. Reducing mortalityrequires in-depth examination of individual causes ofdeath. The five leading causes exhibit different character-istics, degrees of preventability, and contributing factors,with the greatest improvement opportunities identifiedfor hemorrhage and preeclampsia. These findings pro-vide additional support for hospital, state, and nationalmaternal safety programs.(Obstet Gynecol 2015;125:938–47)

DOI: 10.1097/AOG.0000000000000746

LEVEL OF EVIDENCE: II

The past century has seen remarkable progress inimproving the safety of childbirth in the United

States. Maternal mortality fell from 850 per 100,000live births in 1900 to 7.7 per 100,000 in 1997.1 Overthe past 20 years, however, this decline hasreversed.2 The 2009 U.S. pregnancy-related mortal-ity rate was 17.8 deaths per 100,000 live births,above that of other high-resource countries.2,3 Thisrise has prompted a renewed focus at national andstate levels to examine the causes and contributingfactors of maternal death and improve public healthand clinical practice.4,5

Most previous studies of pregnancy-relateddeaths have included demographic and limited clin-ical information but did not compare specific causesof death for factors other than preventability.3,6–8

Studies focused on a single cause of pregnancy-related mortality often were based on administrativedata sets with limited access to clinical records andunable to identify improvement opportunities.9–11

One of every eight U.S. births occurs in California,resulting in more than 500,000 annual deliveries withextensive racial and ethnic diversity. The California

From the California Maternal Quality Care Collaborative, Stanford University,Palo Alto, California Pacific Medical Center, San Francisco, the Public HealthInstitute, Santa Cruz, the Department of Family and Community Medicine,University of California, San Francisco, School of Medicine, San Francisco, andthe Maternal, Child and Adolescent Health Division, Center for Family Health,California Department of Public Health, Sacramento, California.

This project was made possible by Federal Title V MCH block grant funding fromthe California, Department of Public Health (CDPH), Maternal Child andAdolescent Health (MCAH) Division.

The authors thank the California Pregnancy-Associated Mortality Review Com-mittee for their careful case reviews and Dr. Connie Mitchell, Deputy Director,CDPH Center for Family Health, and Dr. Shabbir Ahmad, Chief, MCAHEpidemiology, Assessment, and Program Development, for their ongoing supportof the California Pregnancy-Associated Mortality Review project.

Corresponding author: Elliott K. Main, MD, CMQCC, Stanford University,1265 Welch Road, MS 5415, Palo Alto, CA 94305; e-mail: [email protected].

Financial DisclosureThe authors did not report any potential conflicts of interest.

© 2015 by The American College of Obstetricians and Gynecologists. Publishedby Wolters Kluwer Health, Inc. All rights reserved.ISSN: 0029-7844/15

938 VOL. 125, NO. 4, APRIL 2015 OBSTETRICS & GYNECOLOGY

Copyright ª by The American College of Obstetriciansand Gynecologists. Published by Wolters Kluwer Health, Inc.

Unauthorized reproduction of this article is prohibited.

Obstet Gynecol. 2015;125(4):938–47.

Preeclampsia deaths were most common amongforeign-born Hispanic and African American womenand were associated with early gestational age, consistentwith studies demonstrating the increased severity ofearly-onset preeclampsia.17 This cause of death wasdeemed one of the most preventable, with high ratesof delayed response to symptoms and vital signs, inef-fective control of hypertension, inadequate staffknowledge around blood pressure management,misdiagnosis, and lack of continuity of care. Patientfactors included lack of understanding of warningsigns and delays in seeking care. These findingsreinforce the ongoing work to promote better

clinical recognition and response to preeclampsiaand eclampsia. Recently, the California MaternalQuality Care Collaborative, Hospital Corporation ofAmerica, and the American College of Obstetriciansand Gynecologists released guidelines and qualityimprovement tool kits with standardized approachesto recognize and treat severe hypertension and toincrease awareness of atypical clinical presentationsand patient education.17–19

Hemorrhage deaths occurred among women whowere significantly older, multiparous, of normalweight, and who had premature births. In this study,35% of hemorrhage deaths were related to placental

0 10

Amniotic fluid embolism‡ (n=18)

Venous thromboembolism (n=20)

Obstetric hemorrhage† (n=20)

Preeclampsia or eclampsia† (n=35)

Cardiovascular disease (n=48)

Other (n=64)

All deaths (n=205)

20 30 40 50 60 70 80 90 100

Percent of cases

Good-to-strong chance Some chance No chance

41 48 11

39 39 22

83 17

50 45 5

29

60

70

63 8

40

25 5

Fig. 3. Chance to alter outcomeamong major causes of pregnancy-related death (n5205*), California,2002–2005. *The California Preg-nancy-Associated Mortality ReviewCommittee was unable to determinepreventability in one cardiovasculardisease death and one eclampsiadeath. †Significantly more likely tohave good-to-strong chance thancardiovascular disease deaths andamniotic fluid embolism deaths.‡Significantly less likely to have good-to-strong chance than all causes.Main. Pregnancy-Related Mortality inCalifornia. Obstet Gynecol 2015.

Days between delivery and maternal death (n)

0 3 126 9 15 18 21 24 27 30 33 36 39 42 45 48 51

0 20 40 60 80 100 120140 160 180200 220 240 260 280 300 320 340

Amniotic fl uid embolism* (n=18)

Venous thromboembolism (n=20)

Obstetric hemorrhage* (n=20)

Preeclampsia or eclampsia (n=36)

Cardiovascular disease† (n=49)

Fig. 2. Timing of death among majorcauses of pregnancy-related death(n5143), California, 2002–2005.Boxes represent the 25th to 75thcentile ranges. Vertical lines indicatethe median. Whiskers represent the10th and 90th centile limits, withoutliers shown beyond (circles andstars). *Significantly closer to deliverythan venous thromboembolism andcardiovascular disease deaths (P,.05).†Significantly further from deliverythan amniotic fluid embolism, hemor-rhage, and preeclampsia or eclampsia(P,.001).Main. Pregnancy-Related Mortality in Cal-ifornia. Obstet Gynecol 2015.

944 Main et al Pregnancy-Related Mortality in California OBSTETRICS & GYNECOLOGY



Obstet Gynecol. 2015;125(4):938–47.

complications compared with 16% found in an earliernational study.9 We found high rates of preventabilityamong hemorrhage deaths, similar to other research.6

We identified very high rates of health care providerfactors, including delayed response to clinical warningsigns, ineffective medication, and inadequate bloodproduct utilization. Hemorrhage deaths had the high-est rates of facility contributing factors. U.K. andFrench reviews noted 66% of hemorrhage casesinvolved suboptimal care among health care pro-viders and facilities.15,16 Recent studies indicate thatstandardized approaches to obstetric hemorrhagereduce serious morbidity.20,21

Venous thromboembolism pregnancy-related mor-tality rates were highest in African American women,obese women, and among women who had repeat

cesarean deliveries. Half of the venous thromboembo-lism deaths were highly preventable, with strongimprovement opportunities related to appropriatevenous thromboembolism prophylaxis and improvedresponses to clinical warning signs. The UnitedKingdom noted a similar relationship with obesityand cesarean delivery, whereas France noted 61%had suboptimal care.15,16 Currently, the U.S. mater-nity care and safety community is discussing recom-mendations for additional approaches for preventionof venous thromboembolism based on risk factorsbeyond universal sequential compression devices atcesarean delivery.4

Women who died from amniotic fluid embolismpresented largely in their 30s, were more likely to bemultiparas, and to have term births. Other

Cardiovasculardisease(n=49)

0

20

40

60

80

100

Perc

ent o

f cas

es

A

0

20

40

60

80

100

0

20

40

60

80

100

Perc

ent o

f cas

esPe

rcen

t of c

ases

Preeclampsiaor eclampsia

(n=36)

Obstetrichemorrhage

(n=20)

Venousthromboembolism

(n=20)

Amniotic fl uidembolism

(n=18)



(n=36)

Obstetrichemorrhage

(n=20)


(n=20)


(n=18)

B



(n=36)

Obstetrichemorrhage

(n=20)


(n=20)


(n=18)

Delayed response to clinical warning signsIneffective care

MisdiagnosisLack of continuity of careFailure to consult

Inadequate knowledgeCoordination of careInadequate servicesInadequate equipmentSystems issues

ObesityDelay in seeking care

Lack of knowledge

Substance abuse

Refusal of medical advice

Underlying medical condition

C

Pregnancy-related deaths due to healthcare provider factors

Pregnancy-related deaths due to facility factors

Pregnancy-related deaths due to patient factors

Fig. 4. Contributing factors amongmajor causes of pregnancy-relateddeath, California, 2002–2005.Health care provider factors (A),facility factors (B), and patientfactors (C).Main. Pregnancy-Related Mortality inCalifornia. Obstet Gynecol 2015.

VOL. 125, NO. 4, APRIL 2015 Main et al Pregnancy-Related Mortality in California 945



TIMING OF DELIVERY

Review Article

Management of pre-eclampsia: issues for anaesthetistsA. T. Dennis

Director of Anaesthesia Research, Department of Anaesthesia, The Royal Women’s Hospital Parkville and ClinicalAssociate Professor, Department of Pharmacology, The University of Melbourne, Victoria, Australia

SummaryPre-eclampsia is a leading cause of maternal morbidity and mortality. Substandard care is often present and many deathsare preventable. The aim of this review is to summarise the key management issues for anaesthetists in the light of thecurrent literature. A systematic literature search of electronic databases was undertaken including MEDLINE, EMBASEand the Cochrane Library using the key words obstetrics, pregnancy, pregnancy complications, maternal, pre-eclampsia,preeclampsia, cardiac function, haemodynamics, haemolysis, elevated liver enzymes, low platelets (HELLP), eclampsia,anaesthesia, anesthesia, neuraxial. Relevant Colleges and Societies websites were examined for pertinent guidelines. Thedisease is defined within the context of hypertensive diseases, and early recognition of pre-eclampsia and itscomplications, as well as multidisciplinary expert team management is highlighted. Accurate monitoring and recordingof observations including the use of transthoracic echocardiography is discussed. The importance of the treatment ofsystolic blood pressure > 180 mmHg and the use of intravenous antihypertensive medication as well as the use ofparenteral magnesium sulphate for the treatment and prevention of eclampsia is emphasised . Restricted intravenousfluid therapy and avoidance of ergometrine is discussed. Neuraxial analgesia and anaesthesia, and general anaesthesia forbirth is summarised as well as postpartum management including analgesia, thromboprophylaxis, management of acutepulmonary oedema and the use of pharmacological agents in the setting of breastfeeding.................................................................................................................................................................

Correspondence to: A. DennisEmail: [email protected]

Accepted: 13 April 2012

Pre-eclampsia is a multisystem disease unique to humanpregnancy characterised by hypertension and organsystem involvement. The disease is responsible forconsiderable morbidity and mortality, complicating5–8% of pregnancies. Deaths are due to intracranialhaemorrhage and cerebral infarction, acute pulmonaryoedema, respiratory failure and hepatic failure orrupture [1, 2]. Severe maternal complications includeantepartum haemorrhage due to placental abruption,eclampsia, cerebrovascular accidents, organ failureand disseminated intravascular coagulation [1–4].Pre-eclampsia is the leading cause of fetal growth

restriction, intrauterine fetal demise and preterm birth[2, 5].

Women who experience pre-eclampsia are atincreased risk of hypertension, cerebrovascular diseaseand ischaemic heart disease, in later life [6–11]. Anaes-thetists are frequently involved in the multi-disciplinarymanagement of critically ill women with pre-eclampsia,and clinical practice should be based on currentscientific evidence.

This article was developed as there was a need toprovide a current succinct summary of the anaestheticissues relating to the care of women with pre-eclampsia

Anaesthesia 2012 doi:10.1111/j.1365-2044.2012.07195.x

Anaesthesia ª 2012 The Association of Anaesthetists of Great Britain and Ireland 1

Anaesthesia. 2012;67(9):1009–20.

Anaesthesia. 2012;67(9):1009–20.

other aetiologies. These include renal disease, phaeo-chromocytoma, drug usage such as cocaine andamphetamines and cardiovascular diseases such ascoarctation, subclavian stenosis, aortic dissection andvasculitis.

Under extremely rare circumstances, pre-eclampsiamay develop before 20 weeks’ gestation in the setting ofa hydatidiform mole, multiple pregnancy, fetal orplacental abnormalities, antiphospholipid syndrome orsevere renal disease [18, 29].

Organisational aspects of careMultidisciplinary team approachThe significance of an experienced multidisciplinary teamapproach to the management of women with pre-eclamp-sia has been highlighted in many recent publications [1, 2,4, 30, 31]. A common message is the importance of early

referral, involving the anaesthetist in the management [4,31, 32] and ensuring that the woman with severepre-eclampsia is stabilised before delivery [2, 4, 19].

Maintenance of clinical skillsIn the most recent Confidential Enquiries into MaternalDeaths, the maintenance of clinical skills was high-lighted as a major factor in reducing morbidity andmortality [1]. Particular emphasis was placed on regularaudited training of all clinical staff for the earlyrecognition and management of severely ill pregnantwomen [1, 2].

The use of an obstetric early warning chart has beenproposed as an important clinical tool that may allow formore timely recognition of those women who aredeveloping a critical illness [1, 2]. Widespread adoptionof generic reportable parameters also allows bench-marking both nationally and internationally for out-comes in women with pre-eclampsia [33, 34].

Reduction of high blood pressureNon-severe hypertensionNon-severe hypertension is defined as blood pressurewith a systolic level of 140–159 mmHg and a diastolic of90–109 mmHg. In a recent systematic review, there wereno clear differences when antihypertensive interventionswere compared with placebo or with no intervention, orwhen two anti-hypertensive medications were com-pared. Due to the risk of haemorrhagic stroke in thepresence of systolic hypertension, most guidelinesrecommend lowering of non-severe blood pressure toa systolic level of 140–150 mmHg and a diastolic of 90–100 mmHg, using oral labetalol as the drug of choice[20, 35]. Thresholds vary depending on the existence ofco-morbidities.

Safe agents include methyldopa, labetalol, nifedipineor isradipine, and some b-adrenoceptor blockers (meto-prolol, pindolol, propranolol) and low-dose diazoxide[36]. Atenolol is not recommended due to fetal growthrestriction. Angiotensin converting enzyme inhibitorsand angiotensin type-2 receptor blockers are contrain-dicated (19, 37, 38; Level 3).

Severe hypertensionSevere hypertension is defined as systolic pressure‡ 160 mmHg or diastolic pressure ‡ 110 mmHg and

Table 3 Characteristics of severe pre-eclampsia.

Severe pre-eclampsia threshold level

Hypertension Systolic blood pressure‡ 140 mmHg‡ 160 mmHg – severe hypertension‡ 180 mmHg – hypertensive crisisAnd ⁄ or diastolic blood pressure‡ 90 mmHg‡ 110 mmHg – hypertensive crisis

And one or more of:Centralnervoussystem

Seizures ⁄ eclampsiaHeadacheVisual disturbancesPapilloedemaClonus ⁄ hyperreflexia

Cardiorespiratorysystem

Pulmonary oedema

Gastrointestinalsystem

Elevated liver transaminaseenzymes ‡ 70 IU.l)1

Liver tendernessNausea and vomitingEpigastric pain

Haemoatologicalsystem

HaemolysisThrombocytopenia < 100 · 109.l)1

Disseminated intravascularcoagulation

Renal system Proteinuria > 5 g excreted in 24 h,3 + protein dipstick

Protein ⁄ creatinine > 0.5 g.mmol)1

Urine output < 500 ml in 24 hRenal failure

Uteroplacental ⁄fetal circulation

Placental abruptionIntrauterine growth restrictionUmbilical artery ⁄ uterine arteryblood flow abnormalities – absentor reversed end-diastolic flow

Anaesthesia 2012 Dennis | Management of pre-eclampsia

4 Anaesthesia ª 2012 The Association of Anaesthetists of Great Britain and Ireland

Risk reduction and successful, safe clinical outcomes for women with preeclampsia or eclampsia require avoidance and management of severe systolic and severe diastolic hypertension. How to integrate standardized order sets into everyday safe practice in the United States is a chal-lenge. Increasing evidence indicates that standardization of care improves patient outcomes (1). Introducing into obstetric practice standardized, evidence-based clini-cal guidelines for the management of patients with preeclampsia and eclampsia has been demonstrated to reduce the incidence of adverse maternal outcomes (2, 3). With the advent of pregnancy hypertension guidelines in the United Kingdom, care of maternity patients with preeclampsia or eclampsia improved significantly, and maternal mortality rates decreased because of a reduction in cerebral and respiratory complications (4, 5).

Acute-onset, severe systolic (greater than or equal to 160 mm Hg) or severe diastolic (greater than or equal to 110 mm Hg) hypertension or both can occur in pregnant or postpartum women with any hypertensive disorders during pregnancy. Acute-onset, severe hypertension that is accurately measured using standard techniques and is persistent for 15 minutes or more is considered a hypertensive emergency. This occurs in the second half of gestation in patients not known to have chronic hyper-tension who develop sudden, severe hypertension (ie, with preeclampsia, gestational hypertension, or HELLP

[hemolysis, elevated liver enzymes, low platelets] syn-drome) or, less frequently, in patients with chronic hyper-tension who are developing superimposed preeclampsia with acutely worsening, difficult to control, severe hyper-tension. It is well known that severe hypertension can cause central nervous system injury. Two thirds of the maternal deaths in the most recent Confidential Inquiries report from the United Kingdom for 2003–2005 resulted from either cerebral hemorrhage or infarction (4). The degree of systolic hypertension (as opposed to the level of dia-stolic hypertension or relative increase or rate of increase of mean arterial pressure from baseline levels) may be the most important predictor of cerebral injury and infarction. In a recent case series of 28 women with severe preeclamp-sia and stroke, all but 1 woman had severe systolic hyper-tension (greater than or equal to 160 mm Hg) just before a hemorrhagic stroke, and 54% died, whereas only 13% had severe diastolic hypertension (greater than or equal to 110 mm Hg) in the hours preceding stroke (6). A simi-lar relationship between severe systolic hypertension and risk of hemorrhagic stroke has been observed in nonpreg-nant adults (7). Thus, systolic BP of 160 mm Hg or greater is widely adopted as the definition of severe hypertension in pregnant or postpartum women (8, 9).

Pregnant or postpartum women with acute-onset, severe systolic or severe diastolic hypertension or both require antihypertensive therapy. The goal is not to nor-

Emergent Therapy for Acute-Onset, Severe Hypertension With Preeclampsia or EclampsiaABSTRACT: Acute-onset, persistent (lasting 15 minutes or more), severe systolic (greater than or equal to 160 mm Hg) or severe diastolic hypertension (greater than or equal to 110 mm Hg) or both in pregnant or postpar-tum women with preeclampsia or eclampsia constitutes a hypertensive emergency. Severe systolic hypertension may be the most important predictor of cerebral hemorrhage and infarction in these patients and if not treated expeditiously can result in maternal death. Intravenous labetalol and hydralazine are both considered first-line drugs for the management of acute, severe hypertension in this clinical setting. Close maternal and fetal monitoring by the physician and nursing staff are advised. Order sets for the use of labetalol and hydralazine for the initial man-agement of acute, severe hypertension in pregnant or postpartum women with preeclampsia or eclampsia have been developed.

Committee on Obstetric PracticeThis document reflects emerging clinical and scientific advances as of the date issued and is subject to change. The information should not be construed as dictating an exclusive course of treatment or procedure to be followed.

COMMITTEE OPINIONNumber 514 • December 2011

The American College of Obstetricians and GynecologistsWomen’s Health Care Physicians

Risk reduction and successful, safe clinical outcomes for women with preeclampsia or eclampsia require avoidance and management of severe systolic and severe diastolic hypertension. How to integrate standardized order sets into everyday safe practice in the United States is a chal-lenge. Increasing evidence indicates that standardization of care improves patient outcomes (1). Introducing into obstetric practice standardized, evidence-based clini-cal guidelines for the management of patients with preeclampsia and eclampsia has been demonstrated to reduce the incidence of adverse maternal outcomes (2, 3). With the advent of pregnancy hypertension guidelines in the United Kingdom, care of maternity patients with preeclampsia or eclampsia improved significantly, and maternal mortality rates decreased because of a reduction in cerebral and respiratory complications (4, 5).

Acute-onset, severe systolic (greater than or equal to 160 mm Hg) or severe diastolic (greater than or equal to 110 mm Hg) hypertension or both can occur in pregnant or postpartum women with any hypertensive disorders during pregnancy. Acute-onset, severe hypertension that is accurately measured using standard techniques and is persistent for 15 minutes or more is considered a hypertensive emergency. This occurs in the second half of gestation in patients not known to have chronic hyper-tension who develop sudden, severe hypertension (ie, with preeclampsia, gestational hypertension, or HELLP

[hemolysis, elevated liver enzymes, low platelets] syn-drome) or, less frequently, in patients with chronic hyper-tension who are developing superimposed preeclampsia with acutely worsening, difficult to control, severe hyper-tension. It is well known that severe hypertension can cause central nervous system injury. Two thirds of the maternal deaths in the most recent Confidential Inquiries report from the United Kingdom for 2003–2005 resulted from either cerebral hemorrhage or infarction (4). The degree of systolic hypertension (as opposed to the level of dia-stolic hypertension or relative increase or rate of increase of mean arterial pressure from baseline levels) may be the most important predictor of cerebral injury and infarction. In a recent case series of 28 women with severe preeclamp-sia and stroke, all but 1 woman had severe systolic hyper-tension (greater than or equal to 160 mm Hg) just before a hemorrhagic stroke, and 54% died, whereas only 13% had severe diastolic hypertension (greater than or equal to 110 mm Hg) in the hours preceding stroke (6). A simi-lar relationship between severe systolic hypertension and risk of hemorrhagic stroke has been observed in nonpreg-nant adults (7). Thus, systolic BP of 160 mm Hg or greater is widely adopted as the definition of severe hypertension in pregnant or postpartum women (8, 9).

Pregnant or postpartum women with acute-onset, severe systolic or severe diastolic hypertension or both require antihypertensive therapy. The goal is not to nor-

Emergent Therapy for Acute-Onset, Severe Hypertension With Preeclampsia or EclampsiaABSTRACT: Acute-onset, persistent (lasting 15 minutes or more), severe systolic (greater than or equal to 160 mm Hg) or severe diastolic hypertension (greater than or equal to 110 mm Hg) or both in pregnant or postpar-tum women with preeclampsia or eclampsia constitutes a hypertensive emergency. Severe systolic hypertension may be the most important predictor of cerebral hemorrhage and infarction in these patients and if not treated expeditiously can result in maternal death. Intravenous labetalol and hydralazine are both considered first-line drugs for the management of acute, severe hypertension in this clinical setting. Close maternal and fetal monitoring by the physician and nursing staff are advised. Order sets for the use of labetalol and hydralazine for the initial man-agement of acute, severe hypertension in pregnant or postpartum women with preeclampsia or eclampsia have been developed.

Committee on Obstetric PracticeThis document reflects emerging clinical and scientific advances as of the date issued and is subject to change. The information should not be construed as dictating an exclusive course of treatment or procedure to be followed.

COMMITTEE OPINIONNumber 514 • December 2011

The American College of Obstetricians and GynecologistsWomen’s Health Care Physicians

2 Committee Opinion No. 514

malize BP, but to achieve a range of 140–160/90–100 mmHg in order to prevent repeated, prolonged expo-sure of the patient to severe systolic hypertension, with subsequent loss of cerebral vasculature autoregulation. When this happens, maternal stabilization should occur before delivery, even in urgent circumstances (10). When acute-onset, severe hypertension is diagnosed in the office setting, the patient should be sent to the hospital expedi-tiously for treatment. Also, if transfer to a tertiary center is likely (eg, for preterm severe preeclampsia), BP should be stabilized and other measures instituted as appropriate, such as magnesium sulfate before transfer. Another risk for severe hypertension is endotracheal intubation, an inter-vention that is well known to increase BP sometimes to severe levels that require emergent therapeutic interven-tion (10). Induction of general anesthesia and intubation should never be undertaken without first taking steps to eliminate or minimize the hypertensive response to intu-bation. Close maternal and fetal monitoring by the physi-cian and nursing staff are advised during the treatment of acute-onset, severe hypertension, and judicious fluid administration is recommended even in the case of oligu-ria. After initial stabilization, the team should monitor BP closely and institute maintenance therapy as needed.

Recommendations

First-Line Therapy Intravenous labetalol and hydralazine are both consid-ered first-line medications for the management of acute-onset, severe hypertension in pregnant and postpartum women; less information currently exists for the use of calcium channel blockers for this clinical indication. Patients may respond to one drug and not the other. Magnesium sulfate is not recommended as an antihyper-tensive agent, but magnesium sulfate remains the drug of choice for seizure prophylaxis in severe preeclampsia and for controlling seizures in eclampsia. Box 1 and Box 2 outline order sets for the use of labetalol and hydralazine for the initial management of acute-onset, severe hyper-tension in pregnant or postpartum women with pre-eclampsia or eclampsia (11). Although both medications are appropriately used for the treatment of hypertensive emergencies in pregnancy, each agent can be associated with adverse effects. Parenteral hydralazine may increase the risk of maternal hypotension (systolic BP 90 mm Hg or less) (11). Parenteral labetalol may cause neonatal bradycardia and should be avoided in women with asthma or heart failure (12, 13). No significant changes in umbilical blood flow have been observed with the use of either labetalol or hydralazine (14), and maternal and perinatal outcomes are similar for both drugs (15). If intravenous access is not yet obtained and treatment for acute-onset, severe hypertension is urgently needed, a 200 mg-dose of labetalol can be administered orally and repeated in 30 minutes if an appropriate improvement is not observed (5).

Second-Line Therapy In the rare circumstance that intravenous bolus labetalol or hydralazine or both fail to relieve acute-onset, severe hypertension and are given in successive appropriate doses such as those outlined in the order sets (see Box 1 and Box 2), emergent consultation with an anesthesiolo-gist, maternal–fetal medicine subspecialist, or critical care specialist to discuss second-line intervention is recom-mended. Second line alternatives to consider include labetalol or nicardipine by infusion pump (16–18).

Box 1. Order Set for Severe Intrapartum or Postpartum Hypertension Initial

First-Line Management With Labetalol*

1. Notify physician if systolic BP measurement is greater than or equal to 160 mm Hg or if diastolic BP mea-surement is greater than or equal to 110 mm Hg.

2. Institute fetal surveillance if undelivered and fetus is viable.

3. Administer labetalol (20 mg IV over 2 minutes). 4. Repeat BP measurement in 10 minutes and record

results. 5. If either BP threshold is still exceeded, administer

labetalol (40 mg IV over 2 minutes). If BP is below threshold, continue to monitor BP closely.

6. Repeat BP measurement in 10 minutes and record results.

7. If either BP threshold is still exceeded, administer labetalol (80 mg IV over 2 minutes). If BP is below threshold, continue to monitor BP closely.


9. If either BP threshold is still exceeded, administer hydralazine (10 mg IV over 2 minutes). If BP is below threshold, continue to monitor BP closely.


11. If either BP threshold is still exceeded, obtain emer-gency consultation from maternal–fetal medicine, internal medicine, anesthesia, or critical care spe-cialists.

12. Give additional antihypertensive medication per spe-cific order.

13. Once the aforementioned BP thresholds are achieved, repeat BP measurement every 10 minutes for 1 hour, then every 15 minutes for 1 hour, then every 30 min-utes for 1 hour, and then every hour for 4 hours.

14. Institute additional BP timing per specific order.

Abbreviations: BP, blood pressure; IV, intravenously.*See text for important adverse effects and contraindications.Data from Report of the National High Blood Pressure Education Program Working Group on High Blood Pressure in Pregnancy. Am J Obstet Gynecol 2000;183:S1–S22.

ANTIHYPERTENSIVE TREATMENT

140-150 / 80-10010-20 mmHg every 10-20 minutes

Circulation.2014;130(8):703–14.

OBSTETRICS

Maternal mortality in the United States: predictability and theimpact of protocols on fatal postcesarean pulmonaryembolism and hypertension-related intracranial hemorrhageSteven L. Clark, MD; James T. Christmas, MD; Donna R. Frye, RN; Janet A. Meyers, RN; Jonathan B. Perlin, MD, PhD

OBJECTIVE: The purpose of this study was to examine the efficacy ofspecific protocols that have been developed in response to a previousanalysis of maternal deaths in a large hospital system. We alsoanalyzed the theoretic impact of an ideal system of maternal triage andtransport on maternal deaths and the relative performance of cause ofdeath determination from chart review compared with a review ofdischarge coding data.

STUDY DESIGN: We conducted a retrospective evaluation of maternaldeaths from 2007-2012 after the introduction of disease-specificprotocols that were based on 2000-2006 data.

RESULTS:Our maternal mortality rate was 6.4 of 100,000 births in just>1.2 million deliveries. A policy of universal use of pneumaticcompression devices for all women who underwent cesarean deliveryresulted in a decrease in postoperative pulmonary embolism deathsfrom 7 of 458,097 cesarean births to 1 of 465,880 births (P¼ .038). A

policy that involved automatic and rapid antihypertensive therapy fordefined blood pressure thresholds eliminated deaths from in-hospitalintracranial hemorrhage and reduced overall deaths from pre-eclampsia from 15-3 (P¼ .02.) From 1-3 deaths were related causallyto cesarean delivery. Only 7% of deaths were potentially preventablewith an ideal system of admission triage and transport. Cause of deathanalysis with the use of discharge coding data was correct in 52% ofcases.

CONCLUSION: Disease-specific protocols are beneficial in thereduction of maternal death because of hypertensive disease andpostoperative pulmonary embolism. From 2-6 women die annually inthe United States because of cesarean delivery itself. A reduction indeaths from postpartum hemorrhage should be the priority formaternal death prevention efforts in coming years in the United States.

Key words: checklist, maternal mortality rate, patient safety

Cite this article as: Clark SL, Christmas JT, Frye DR, et al. Maternal mortality in the United States: predictability and the impact of protocols on fatal postcesareanpulmonary embolism and hypertension-related intracranial hemorrhage. Am J Obstet Gynecol 2014;211:32.e1-9.

M aternal mortality rates in theUnited States have remained

unchanged for several decades, withsome data suggesting a recent increase insuch deaths.1-3 In 2008, we published areview of maternal deaths in approxi-mately 1.5 million births from 2000-2006 and drew a number of conclusionsregarding the potential value of severalspecific steps to address this issue effec-tively in our system and in the nationas a whole.1 These steps included pro-tocols that were directed at prevention

of death from postcesarean pulmonaryembolism, intracranial hemorrhage inwomen with hypertensive crisis, andpostpartum hemorrhage.1,4-6We presenta 6-year observation, detailing clinicalresults of these efforts. In the currentstudy, we also sought to examine theissue of predictability of maternal deathand the potential impact of an idealsystem of risk identification and trans-port on maternal mortality rates. Finally,we examined the correlation betweendiagnostic accuracy regarding the causeof death that was obtained from codingdata, and the data that were obtainedfrom medical records review.Because maternal death commonly is

defined as deaths per 100,000 live birthsand may include deaths that are associ-ated with early pregnancy loss or still-birth, the use of the term maternalmortality ratio to describe these deathsstatistically would be correct. However,

because the term maternal mortality rateis used almost exclusively throughoutthe literature to describematernal deathsduring pregnancy, we have observed thisconvention throughout this article.

METHODS

The Hospital Corporation of Americaencompasses 110 maternal/newborn fa-cilities in 21 states. Our annual deliveryvolume is approximately 210,000 orroughly 5-6% of all births in the UnitedStates. Our present study consisted of 3parts.

Part 1After a review of maternal deaths thatoccurred in our system from 2000-2006,we developed 3 specific patient safetyprograms that were aimed at reductionin maternal deaths. (1) All affiliated hos-pitals instituted the universal use of intra-and postoperative pneumatic compres-sion devices in women who undergocesarean delivery.1,4 (2) We introducedspecific checklist-based protocols that

From the Hospital Corporation of America,Nashville, TN.

Received Dec. 4, 2013; revised Feb. 8, 2014;accepted March 12, 2014.

The authors report no conflict of interest.

Reprints not available from the authors.

0002-9378/freeª 2014 Published by Mosby, Inc.http://dx.doi.org/10.1016/j.ajog.2014.03.031

See related editorial, page 1

32.e1 American Journal of Obstetrics & Gynecology JULY 2014

Research www.AJOG.org

Am J Obstet Gynecol; 2014;211(1):32.e1–9.

FIGURE 2Blood pressure management of severe intrapartum or postpartum hypertension with labetalol

Checklist.IV, intravenously; q, every.

Clark. Maternal mortality in the United States. Am J Obstet Gynecol 2014.

www.AJOG.org Obstetrics Research

JULY 2014 American Journal of Obstetrics & Gynecology 32.e4

Am J Obstet Gynecol; 2014;211(1):32.e1–9.

FIGURE 2Blood pressure management of severe intrapartum or postpartum hypertension with labetalol

Checklist.IV, intravenously; q, every.

Clark. Maternal mortality in the United States. Am J Obstet Gynecol 2014.

www.AJOG.org Obstetrics Research

JULY 2014 American Journal of Obstetrics & Gynecology 32.e4

≥ 160 ≥ 110 inform physician 20 mg Labetalol i.v.

10 min. ≥ 160 / 110 40 mg Labetalol i.v.

10 min. ≥ 160 / 110 60 mg Labetalol i.v.

10 min. ≥ 160 / 110 10 mg Hydralazine

4g initial dose1-2 g/h

severe preeclampsia

preeclampsie Basel 16 handout

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Transcript of preeclampsie Basel 16 handout