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Emergent Therapy for Acute-Onset, Severe Hypertension With Preeclampsia or Eclampsia

The American College of Obstetricians and Gynecologists
Women’s Health Care Physicians
COMMITTEE OPINION
Number 514 • December 2011
Committee on Obstetric Practice
This 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.
Emergent Therapy for Acute-Onset, Severe Hypertension With Preeclampsia or Eclampsia
ABSTRACT: 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.

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-

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).

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).

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.
   
8. Repeat BP measurement in 10 minutes and record results.
   
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.
   
10. Repeat BP measurement in 20 minutes and record results.
    
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. Giveadditionalantihypertensivemedicationperspe- cific order.
    
13. OncetheaforementionedBPthresholdsareachieved, 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.

2 Committee Opinion No. 514

References

1. Kirkpatrick DH, Burkman RT. Does standardization of care through clinical guidelines improve outcomes and reduce medical liability? Obstet Gynecol 2010;116:1022–6.
   
2. Menzies J, Magee LA, Li J, MacNab YC, Yin R, Stuart H, et al. Instituting surveillance guidelines and adverse out- comes in preeclampsia. Preeclampsia Integrated Estimate of RiSk (PIERS) Study Group. Obstet Gynecol 2007;110:121–7.
   
3. von Dadelszen P, Sawchuck D, McMaster R, Douglas MJ, Lee SK, Saunders S, et al. The active implementation of pregnancy hypertension guidelines in British Columbia. Translating Evidence-Based Surveillance and Treatment Strategies (TESS) Group. Obstet Gynecol 2010;116:659–66.
   
4. Saving Mothers’ Lives: reviewing maternal deaths to make motherhood safer: 2006–08. The Eighth Report on Con- fidential Enquiries into Maternal Deaths in the United King- dom. Centre for Maternal and Child Enquiries (CMACE). BJOG 2011;118(suppl 1):1–203.
   
5. TuffnellDJ,JankowiczD,LindowSW,LyonsG,MasonGC, Russell IF, et al. Outcomes of severe pre-eclampsia/eclamp- sia in Yorkshire 1999/2003. Yorkshire Obstetric Critical Care Group. BJOG 2005;112:875 – 80.
   
6. MartinJNJr,ThigpenBD,MooreRC,RoseCH,CushmanJ, May W. Stroke and severe preeclampsia and eclampsia: a paradigm shift focusing on systolic blood pressure. Obstet Gynecol 2005;105:246 – 54.
   
7. Lindenstrom E, Boysen G, Nyboe J. Influence of systolic and diastolic blood pressure on stroke risk: a prospective observational study. Am J Epidemiol 1995;142:1279 – 90.
   
8. Diagnosis,evaluation,andmanagementofthehypertensive disorders of pregnancy. SOGC Clinical Practice Guideline No. 206. Society of Obstetricians and Gynaecologists of Canada. J Obstet Gynaecol Can 2008;30(suppl 1):S1–S48.
   
9. Confidential Enquiries into Maternal Deaths. Why moth- ers die 1997–1999. The fifth report of the Confidential Enquiries into Maternal Deaths in the United Kingdom. London (UK): RCOG Press; 2001.
   
10. Lyons G. Saving mothers’ lives: confidential enquiry into maternal and child health 2003–5. Int J Obstet Anesth 2008;17:103–5.
    
11. Report of the National High Blood Pressure Education Program Working Group on High Blood Pressure in Preg- nancy. Am J Obstet Gynecol 2000;183:S1–S22.
    
12. Magee LA, Cham C, Waterman EJ, Ohlsson A, von Dadelszen P. Hydralazine for treatment of severe hyper- tension in pregnancy: meta-analysis. BMJ 2003;327:955–60.
    
13. Magee LA, von Dadelszen P. The management of severe hypertension. Semin Perinatol 2009;33:138–42.
    
14. Baggio MR, Martins WP, Calderon AC, Berezowski AT, Marcolin AC, Duarte G, et al. Changes in fetal and maternal Doppler parameters observed during acute severe hyper- tension treatment with hydralazine or labetalol: a random- ized controlled trial. Ultrasound Med Biol 2011;37:53–8.
    
15. Duley L, Henderson-Smart DJ, Meher S. Drugs for treat- ment of very high blood pressure during pregnancy. Cochrane Database of Systematic Reviews 2006, Issue 3. Art. No.: CD001449. DOI: 10.1002/14651858.CD001449. pub2.
    

Box 2. Order Set for Severe Intrapartum or Postpartum Hypertension Initial First-Line Management With Hydralazine*

1. Notify physician if systolic BP is greater than or equal to 160 mm Hg or if diastolic BP is greater than or equal to 110 mm Hg.
   
2. Institute fetal surveillance if undelivered and fetus is viable.
   
3. Administer hydralazine (5 mg or 10 mg IV over 2 minutes).
   
4. Repeat BP measurement in 20 minutes and record results.
   
5. 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.
   
6. Repeat BP measurement in 20 minutes and record results.
   
7. If either BP threshold is still exceeded, administer labetalol (20 mg IV over 2 minutes). If BP is below threshold, continue to monitor BP closely.
   
8. Repeat BP measurement in 10 minutes and record results.
   
9. If either BP threshold is still exceeded, administer labetalol (40 mg IV over 2 minutes) and obtain emer- gency consultation from maternal–fetal medicine, internal medicine, anesthesia, or critical care spe- cialists.
   
10. Give additional antihypertensive medication per specific order.
    
11. OncetheaforementionedBPthresholdsareachieved, 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.
    
12. 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.

Transplacental passage is minimal, as are changes in umbilical artery Doppler velocimetry (19).
Sodium nitroprusside should be reserved for extreme emergencies and used for the shortest amount of time possible because of concerns about cyanide and thio- cyanate toxicity in the mother and fetus or newborn and increased intracranial pressure with potential worsening of cerebral edema in the mother (11). Once the hyperten- sive emergency is treated, a complete and detailed evalu- ation of maternal and fetal well-being is needed with, among many issues, consideration of need for subsequent pharmacotherapy and appropriate timing of delivery.

Committee Opinion No. 514 3

16. Prometheus Laboratories Inc. Trandate® (labetalol hydro- chloride) tablets. San Diego (CA): Prometheus Labora- tories; 2010. Available at: http://www.prometheuslabs.com/ Resources/PI/TrandateTab.pdf. Retrieved August 25, 2011.
    
17. Vadhera RB, Pacheco LD, Hankins GD. Acute antihyper- tensive therapy in pregnancy-induced hypertension: is nicardipine the answer? Am J Perinatol 2009;26:495 – 9.
    
18. Nij Bijvank SW, Duvekot JJ. Nicardipine for the treatment of severe hypertension in pregnancy: a review of the litera- ture. Obstet Gynecol Surv 2010;65:341–7.
    
19. Carbonne B, Jannet D, Touboul C, Khelifati Y, Milliez J. Nicardipine treatment of hypertension during pregnancy. Obstet Gynecol 1993;81:908 –14.
    

Copyright December 2011 by the American College of Obstetricians and Gynecologists, 409 12th Street, SW, PO Box 96920, Washington, DC 20090-6920. All rights reserved. No part of this publication may be reproduced, stored in a retrieval system, posted on the Internet, or transmitted, in any form or by any means, electronic, mechani- cal, photocopying, recording, or otherwise, without prior written per- mission from the publisher. Requests for authorization to make photocopies should be directed to: Copyright Clearance Center, 222 Rosewood Drive, Danvers, MA 01923, (978) 750-8400.
ISSN 1074-861X
Emergent therapy for acute-onset, severe hypertension with pre- eclampsia or eclampsia. Committee Opinion No. 514. American College of Obstetricians and Gynecologists. Obstet Gynecol 2011;118: 1465–8.

4 Committee Opinion No. 514 

TURNOS EN SALA DE PARTOS

DIA	FECHA	SALA DE PARTOS
LUNES	15/09/2014	TATIANA - LAURA - LISETH
MARTES	16/09/2014	DAYANN - ALEXANDRA - GLORIA
MIÉRCOLES	17/09/2014	JUAN CARLOS - FIDEL - FABIO
JUEVES	18/09/2014	TATIANA - LAURA - LISETH
VIERNES	19/09/2014	ALEXANDRA - GLORIA - JUAN CARLOS
SÁBADO	20/09/2014	LISETH - FIDEL - FABIO
DOMINGO DIA	21/09/2014	DAYANN - TATIANA - LAURA
DOMINGO NOCHE	21/09/2014	ALEXANDRA - GLORIA - JUAN CARLOS
LUNES	22/09/2014	DAYANN - FIDEL - FABIO
MARTES	23/09/2014	TATIANA - LAURA - LISETH
MIÉRCOLES	24/09/2014	DAYANN - ALEXANDRA - JUAN CARLOS
JUEVES	25/09/2014	GERMAN - FIDEL - DIEGO
VIERNES	26/09/2014	TATIANA - LISETH - MARTHA
SÁBADO	27/09/2014	DAYANN - ALEXANDRA - GERMAN
DOMINGO DIA	28/09/2014	JUAN CARLOS - FIDEL - DIEGO
DOMINGO NOCHE	28/09/2014	TATIANA - LISETH - MARTHA
LUNES	29/09/2014	DAYANN - ALEXANDRA - GERMAN
MARTES	30/09/2014	JUAN CARLOS - FIDEL - DIEGO
MIÉRCOLES	01/10/2014	TATIANA - LISETH - MARTHA
JUEVES	02/10/2014	DAYANN - ALEXANDRA - GERMAN
VIERNES	03/10/2014	JUAN CARLOS - FIDEL - DIEGO
SÁBADO	04/10/2014	LISETH - MARTHA - TATIANA
DOMINGO DIA	05/10/2014	JUAN CARLOS - FABIO - DIEGO
DOMINGO NOCHE	05/10/2014	DAYANN  - GLORIA - LAURA
LUNES	06/10/2014	JUAN CARLOS - LISETH - MARTHA
MARTES	07/10/2014	LAURA - GERMAN - GLORIA
MIÉRCOLES	08/10/2014	JUAN CARLOS - FABIO - DIEGO
JUEVES	09/10/2014	LAURA - LISETH - MARTHA
VIERNES	10/10/2014	DAYANN - GERMAN - GLORIA
SÁBADO	11/10/2014	JUAN CARLOS - FABIO - DIEGO
DOMINGO DIA	12/10/2014	LAURA - LISETH - MARTHA
DOMINGO NOCHE	12/10/2014	DAYANN - GERMAN - GLORIA
LUNES	13/10/2014	JUAN CARLOS - FABIO - DIEGO
MARTES	14/10/2014	LAURA - GLORIA - MARTHA
MIÉRCOLES	15/10/2014	GERMAN - ALEXANDRA - TATIANA
JUEVES	16/10/2014	DIEGO - FIDEL - FABIO
VIERNES	17/10/2014	LAURA - TATIANA - MARTHA
SÁBADO	18/10/2014	GERMAN - FABIO - FIDEL
DOMINGO	19/10/2014	LAURA - TATIANA - MARTHA
LUNES	20/10/2014	GERMAN - FABIO - FIDEL
MARTES (DIA)	21/10/2014	DIEGO - GLORIA - ALEXANDRA
MARTES (NOCHE)	21/10/2014	LAURA - TATIANA - MARTHA
MIÉRCOLES	22/10/2014	DIEGO - ALEXANDRA - GLORIA
JUEVES	23/10/2014	GERMAN - FABIO - FIDEL
VIERNES	24/10/2014	LAURA - TATIANA - MARTHA