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Hypertensive Emergencies in
Pregnancy
Nikita K Joshi MD
Clinical Instructor of Surgery
Emergency Medicine
Stanford University Medical Center

njoshi8@gmail.com
@njoshi8

SUMC | Nikita Joshi, MD (njoshi8@gmail.com)

Slide 1 of 18
Objectives
Diagnostic Criteria
End Organ Consequences
Medical Management

SUMC | Nikita Joshi, MD (njoshi8@gmail.com)

Slide 2 of 18
Diagnostic Criteria

Chronic
(Preexisting)
HTN

Gestational
HTN

SUMC | Nikita Joshi, MD (njoshi8@gmail.com)

Preeclampsia

Severe
Preeclampsia

Eclampsia

Slide 3 of 18
Epidemiology
HTN disorders
complicates 5-10% of
all pregnancies

Preeclampsia
complicates 3-9% of
pregnancies in
developed countries

Accountable for 1015% of maternal
death in developed
countries

SUMC | Nikita Joshi, MD (njoshi8@gmail.com)

Lo JO. Hypertensive disease of pregnancy and maternal mortality. Curr Opin Obstet Gynecol. 2013
Apr;25(2):124-32. PMID: 23403779.

Slide 4 of 18
Morbidity and Mortality
Maternal

Neonatal

HTN
CAD
CVA
ESRD

IUGR
SGA
HTN
CAD

SUMC | Nikita Joshi, MD (njoshi8@gmail.com)

Slide 5 of 18
Risk Factors

Maternal History

Family History

Primipaternity

Fetus

Smoking

Uzan J. Pre-eclampsia: pathophysiology, diagnosis, and management. Vasc Health Risk
Manag. 2011;7:467-74. PMID: 21822394.

SUMC | Nikita Joshi, MD (njoshi8@gmail.com)

Slide 6 of 18
Preeclampsia
Disease of Multiple Theories
Unknown
Etiology

Lack of
animal model

Challenges in Prevention, Screening, Diagnosis, Treatment

Roberts JM. If we know so much about preeclampsia, why haven’t we cured the disease? J Reprod
Immuol. 2013 Sep;99(1-2):1-9. PMID 23890710.

SUMC | Nikita Joshi, MD (njoshi8@gmail.com)

Slide 7 of 18
Current Theory
Abnormal Placentation
Fetal Cytotrophoblasts
fail to adopt invasive
endothelial phenotype

Invasion of spiral
arteries is shallow

Remain small-caliber
resistance vessels
Vikse BE. Preeclampsia and the Risk of End-Stage Renal Disease. NEJM. 2008. Aug 21;359(8):800-9. PMID: 18716297.

SUMC | Nikita Joshi, MD (njoshi8@gmail.com)

Slide 8 of 18
Pathophysiology
Abnormal Placentation

Vasoconstriction
Activation of coagulation cascade
Loss of fluid from intravascular
space

SUMC | Nikita Joshi, MD (njoshi8@gmail.com)

Endothelial Dysfunction

Decreased organ perfusion
Inflammation
Hemorrhage
Ischemia

Slide 9 of 18
End Organ Consequence

Kidney
Glomerular
capillary
endotheliosis and
vasospasm reduce
GFR

Cranial
Vasospasm leading
to
headache, seizures,
CVA

Vision
Retina artery
constriction,visual
changes

Cardiopulm
Capillary leakage
leading to
nondependent
edema, pulm
edema

SUMC | Nikita Joshi, MD (njoshi8@gmail.com)

Liver
reduced hepatic
blood flow leads to
ischemia and
periportal
hemorrhage

Heme
Platelet level
proportional to
severity of disease

Placenta
Placental abruption

Fetus
Growth
restriction, oligoh
ydramnios

Slide 10 of 18
Medical Management
BP Control
Magnesium
Intubation
Delivery

SUMC | Nikita Joshi, MD (njoshi8@gmail.com)

Slide 11 of 18
Hypertensive Therapy

Labetalol
Beta > Alpha Blocker
Vasodilation
10-20 mg IVP
1-2 mg/min up to 300 mg

SUMC | Nikita Joshi, MD (njoshi8@gmail.com)

Hydralazine
Vascular smooth muscle
relaxer
5 mg IVP
0.5-10 mg/hr

Slide 12 of 18
Evidence Review
Cochrane Review 2013
35 Randomized Control Trials
3573 Women included

Not enough evidence to show which drug is most effective
SUMC | Nikita Joshi, MD (njoshi8@gmail.com)

Slide 13 of 18
Treatment Algorithm

Uzan J. Pre-eclampsia: pathophysiology, diagnosis, and management. Vasc Health Risk Manag. 2011;7:467-74. PMID: 21822394.

SUMC | Nikita Joshi, MD (njoshi8@gmail.com)

Slide 14 of 18
Magnesium
2013 Committee Opinion

Prevention &
Treatment of
Seizures

SUMC | Nikita Joshi, MD (njoshi8@gmail.com)

Fetal neural
protection for
preterm
delivery

Short-term
prolongation
of pregnancy
(48 hrs)

Slide 15 of 18
Mechanism of Action
Vasculature
Ca2+ Antagonist
Smooth muscle
relaxation
Vasodilation
Relieve vasospam
Decreased vascular
resistance

Cerebral Endothelium
Ca Antagonist
Decrease stress fiber
contraction
Decrease paracellular
BBB permeability
Limits cerebral edema

Anticonvulsant
NMDA Antagonist
Decreases effect of
glutamate
Limits neuronal
depolarization
Increases seizure
threshold

Euser AG. Magnesium sulfate for the treatment of eclampsia: a brief review. Stroke. 2009. Apr;40(4):1169-75. PMID: 19211496.

SUMC | Nikita Joshi, MD (njoshi8@gmail.com)

Slide 16 of 18
Future Directions

Warrington JP. Recent advances in the understanding of the pathophysiology of preeclampsia. Hypertension. 2013 Oct;62(4):666-73. PMID: 23897068.

Diagnostic Criteria

SUMC | Nikita Joshi, MD (njoshi8@gmail.com)

End Organ
Consequences

Medical
Management

Slide 17 of 18
References
•
•
•

•
•
•
•
•

•
•
•
•
•

Abalos E. Antihypertensive drug therapy for mild to moderate hypertension during pregnancy. Cochrane Database of
Systematic Reviews. 2007 (1), CD0002252.
Berg CJ. Pregnancy-Related mortality in the United States, 1998-2005. Obstet Gynecol. 2010. Dec;116(6):1302-1309.
Duley L. Magnesium sulphate and other anticonvulsants for women with pre-eclampsia. Cochrane Database Syst Rev. 2010 Nov
10;(11):CD000025.
Duley L. Magnesium sulphate versus phenytoin for eclampsia. Cochrane Database Syst Rev. 2010 Oct 6;(10):CD000128.
Duley L. Drugs for treatment of very high blood pressure during pregnancy. Cochrane Database Syst Rev. 2013
Jul31;7:CD001449.
Euser AG. Magnesium sulfate for the treatment of eclampsia: a brief review. Stroke. 2009. Apr;40(4):1169-75. PMID: 19211496.
Lo JO. Hypertensive disease of pregnancy and maternal mortality. Curr Opin Obstet Gynecol. 2013 Apr;25(2):124-32. PMID:
23403779.
Roberts JM. If we know so much about preeclampsia, why haven’t we cured the disease? J Reprod Immuol. 2013 Sep;99(12):1-9. PMID 23890710.
Rosser ML. Preeclampsia: an obstetrician’s perspective. Adv Chronic Kidney Dis. 2013 May;20(3):287-96. PMID: 23929395.
Samadi AR. Maternal hypertension and associated pregnancy complications among african-american and other women in the
United States. Obstet Gynecol. 1996. Apr;87(4):557-63. PMID: 8602308.
Uzan J. Pre-eclampsia: pathophysiology, diagnosis, and management. Vasc Health Risk Manag. 2011;7:467-74. PMID:
21822394.
Vikse BE. Preeclampsia and the Risk of End-Stage Renal Disease. NEJM. 2008. Aug 21;359(8):800-9. PMID: 18716297.
Warrington JP. Recent advances in the understanding of the pathophysiology of preeclampsia. Hypertension. 2013
Oct;62(4):666-73. PMID: 23897068.

SUMC | Nikita Joshi, MD (njoshi8@gmail.com)

Slide 18 of 18

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Hypertensive emergencies in pregnancy

  • 1. Hypertensive Emergencies in Pregnancy Nikita K Joshi MD Clinical Instructor of Surgery Emergency Medicine Stanford University Medical Center njoshi8@gmail.com @njoshi8 SUMC | Nikita Joshi, MD (njoshi8@gmail.com) Slide 1 of 18
  • 2. Objectives Diagnostic Criteria End Organ Consequences Medical Management SUMC | Nikita Joshi, MD (njoshi8@gmail.com) Slide 2 of 18
  • 3. Diagnostic Criteria Chronic (Preexisting) HTN Gestational HTN SUMC | Nikita Joshi, MD (njoshi8@gmail.com) Preeclampsia Severe Preeclampsia Eclampsia Slide 3 of 18
  • 4. Epidemiology HTN disorders complicates 5-10% of all pregnancies Preeclampsia complicates 3-9% of pregnancies in developed countries Accountable for 1015% of maternal death in developed countries SUMC | Nikita Joshi, MD (njoshi8@gmail.com) Lo JO. Hypertensive disease of pregnancy and maternal mortality. Curr Opin Obstet Gynecol. 2013 Apr;25(2):124-32. PMID: 23403779. Slide 4 of 18
  • 5. Morbidity and Mortality Maternal Neonatal HTN CAD CVA ESRD IUGR SGA HTN CAD SUMC | Nikita Joshi, MD (njoshi8@gmail.com) Slide 5 of 18
  • 6. Risk Factors Maternal History Family History Primipaternity Fetus Smoking Uzan J. Pre-eclampsia: pathophysiology, diagnosis, and management. Vasc Health Risk Manag. 2011;7:467-74. PMID: 21822394. SUMC | Nikita Joshi, MD (njoshi8@gmail.com) Slide 6 of 18
  • 7. Preeclampsia Disease of Multiple Theories Unknown Etiology Lack of animal model Challenges in Prevention, Screening, Diagnosis, Treatment Roberts JM. If we know so much about preeclampsia, why haven’t we cured the disease? J Reprod Immuol. 2013 Sep;99(1-2):1-9. PMID 23890710. SUMC | Nikita Joshi, MD (njoshi8@gmail.com) Slide 7 of 18
  • 8. Current Theory Abnormal Placentation Fetal Cytotrophoblasts fail to adopt invasive endothelial phenotype Invasion of spiral arteries is shallow Remain small-caliber resistance vessels Vikse BE. Preeclampsia and the Risk of End-Stage Renal Disease. NEJM. 2008. Aug 21;359(8):800-9. PMID: 18716297. SUMC | Nikita Joshi, MD (njoshi8@gmail.com) Slide 8 of 18
  • 9. Pathophysiology Abnormal Placentation Vasoconstriction Activation of coagulation cascade Loss of fluid from intravascular space SUMC | Nikita Joshi, MD (njoshi8@gmail.com) Endothelial Dysfunction Decreased organ perfusion Inflammation Hemorrhage Ischemia Slide 9 of 18
  • 10. End Organ Consequence Kidney Glomerular capillary endotheliosis and vasospasm reduce GFR Cranial Vasospasm leading to headache, seizures, CVA Vision Retina artery constriction,visual changes Cardiopulm Capillary leakage leading to nondependent edema, pulm edema SUMC | Nikita Joshi, MD (njoshi8@gmail.com) Liver reduced hepatic blood flow leads to ischemia and periportal hemorrhage Heme Platelet level proportional to severity of disease Placenta Placental abruption Fetus Growth restriction, oligoh ydramnios Slide 10 of 18
  • 11. Medical Management BP Control Magnesium Intubation Delivery SUMC | Nikita Joshi, MD (njoshi8@gmail.com) Slide 11 of 18
  • 12. Hypertensive Therapy Labetalol Beta > Alpha Blocker Vasodilation 10-20 mg IVP 1-2 mg/min up to 300 mg SUMC | Nikita Joshi, MD (njoshi8@gmail.com) Hydralazine Vascular smooth muscle relaxer 5 mg IVP 0.5-10 mg/hr Slide 12 of 18
  • 13. Evidence Review Cochrane Review 2013 35 Randomized Control Trials 3573 Women included Not enough evidence to show which drug is most effective SUMC | Nikita Joshi, MD (njoshi8@gmail.com) Slide 13 of 18
  • 14. Treatment Algorithm Uzan J. Pre-eclampsia: pathophysiology, diagnosis, and management. Vasc Health Risk Manag. 2011;7:467-74. PMID: 21822394. SUMC | Nikita Joshi, MD (njoshi8@gmail.com) Slide 14 of 18
  • 15. Magnesium 2013 Committee Opinion Prevention & Treatment of Seizures SUMC | Nikita Joshi, MD (njoshi8@gmail.com) Fetal neural protection for preterm delivery Short-term prolongation of pregnancy (48 hrs) Slide 15 of 18
  • 16. Mechanism of Action Vasculature Ca2+ Antagonist Smooth muscle relaxation Vasodilation Relieve vasospam Decreased vascular resistance Cerebral Endothelium Ca Antagonist Decrease stress fiber contraction Decrease paracellular BBB permeability Limits cerebral edema Anticonvulsant NMDA Antagonist Decreases effect of glutamate Limits neuronal depolarization Increases seizure threshold Euser AG. Magnesium sulfate for the treatment of eclampsia: a brief review. Stroke. 2009. Apr;40(4):1169-75. PMID: 19211496. SUMC | Nikita Joshi, MD (njoshi8@gmail.com) Slide 16 of 18
  • 17. Future Directions Warrington JP. Recent advances in the understanding of the pathophysiology of preeclampsia. Hypertension. 2013 Oct;62(4):666-73. PMID: 23897068. Diagnostic Criteria SUMC | Nikita Joshi, MD (njoshi8@gmail.com) End Organ Consequences Medical Management Slide 17 of 18
  • 18. References • • • • • • • • • • • • • Abalos E. Antihypertensive drug therapy for mild to moderate hypertension during pregnancy. Cochrane Database of Systematic Reviews. 2007 (1), CD0002252. Berg CJ. Pregnancy-Related mortality in the United States, 1998-2005. Obstet Gynecol. 2010. Dec;116(6):1302-1309. Duley L. Magnesium sulphate and other anticonvulsants for women with pre-eclampsia. Cochrane Database Syst Rev. 2010 Nov 10;(11):CD000025. Duley L. Magnesium sulphate versus phenytoin for eclampsia. Cochrane Database Syst Rev. 2010 Oct 6;(10):CD000128. Duley L. Drugs for treatment of very high blood pressure during pregnancy. Cochrane Database Syst Rev. 2013 Jul31;7:CD001449. Euser AG. Magnesium sulfate for the treatment of eclampsia: a brief review. Stroke. 2009. Apr;40(4):1169-75. PMID: 19211496. Lo JO. Hypertensive disease of pregnancy and maternal mortality. Curr Opin Obstet Gynecol. 2013 Apr;25(2):124-32. PMID: 23403779. Roberts JM. If we know so much about preeclampsia, why haven’t we cured the disease? J Reprod Immuol. 2013 Sep;99(12):1-9. PMID 23890710. Rosser ML. Preeclampsia: an obstetrician’s perspective. Adv Chronic Kidney Dis. 2013 May;20(3):287-96. PMID: 23929395. Samadi AR. Maternal hypertension and associated pregnancy complications among african-american and other women in the United States. Obstet Gynecol. 1996. Apr;87(4):557-63. PMID: 8602308. Uzan J. Pre-eclampsia: pathophysiology, diagnosis, and management. Vasc Health Risk Manag. 2011;7:467-74. PMID: 21822394. Vikse BE. Preeclampsia and the Risk of End-Stage Renal Disease. NEJM. 2008. Aug 21;359(8):800-9. PMID: 18716297. Warrington JP. Recent advances in the understanding of the pathophysiology of preeclampsia. Hypertension. 2013 Oct;62(4):666-73. PMID: 23897068. SUMC | Nikita Joshi, MD (njoshi8@gmail.com) Slide 18 of 18

Notes de l'éditeur

  1. Hypertensive disorders of pregnancy are significant contributors to maternal and fetal morbidity and mortalityPreeclampsia and Eclampsia are disease processes that will be encountered in the ED.Hypertension is a common occurrence in pregnancy. As an EM physician it is important to develop understanding of the emergencies that can arise from the development of preeclampsia and eclampsia. In order to develop an approach to diagnosis, stabilization, treatment, and medical management of preeclampsia and eclampsia, the diagnostic criteria and end organ consequences will be discussed.
  2. How to assess for Proteinuria:Spot protein: creatinine ratio (>30 mg/mmol)24 hr urine collection (>300 mg protein)Chronic HTN: preexisting HTN 140/90Gestational HTN: new HTN after 20 wks gestation without proteinuria 140/90Preeclampsia: new HTN after 20 wks AND proteinuria (>300 mg protein in 24 hrs)Severe preeclampsia: preeclampsia with severe HTN 160/110OR protein <1gramOR end organ diseaseCan have nonspecific complaints like headaches, vision changes, nausea, vomiting, epigastric pain, edemaEclampsia: generalized tonic clonic seizures in the absence of known neurologic disease
  3. 10-15% of maternal deaths are associated with preeclampsia and eclampsiaUp to 10% of women have elevated BP during pregnancy – Duley 20093-8% of women in developed countries will get preeclampsia- Carty 20100.56/1000 births are complicated by eclampsia10-15% maternal deaths are directly associated with preeclampsia and eclampsia
  4. 10-15% of maternal deaths are associated with preeclampsia and eclampsiaUp to 10% of women have elevated BP during pregnancy – Duley 20093-8% of women in developed countries will get preeclampsia- Carty 20100.56/1000 births are complicated by eclampsia10-15% maternal deaths are directly associated with preeclampsia and eclampsia
  5. Risk Factors: Nulliparity, FH Pre-eclampsia, Advanced Maternal Age, ObesityPrior disease - HTN, DM, ESRD, Antiphospholipid SyndBaby: twin/molar pregnancyThere is a 20 fold relative risk of mortality for women with preeclampsia prior to 32 wks gestationNew research showing long term consequence of HTN in pregnancy leading to chronic HTN and increased lifetime risk of cardiovascular disease including end stage renal diseaseWomen with pre-existing primary or secondary chronic hypertensionWomen who develop new-onset hypertension in the second trimesterConsequences for baby: 5% stillbirths in infants without congenital abnormalities occurred with those with mothers with preeclampsiaPreterm birth rate – 1/250 women will give birth before 34 weeks from preeclampsia
  6. FIGURE 48-5 Placentation in normal and preeclamptic pregnancies. In normal placental development, invasive cytotrophoblasts of fetal origin invade the maternal spiral arteries, transforming them from small-caliber resistance vessels to high-caliber capacitance vessels capable of providing placental perfusion adequate to sustain the growing fetus. During the process of vascular invasion, the cytotrophoblasts differentiate from an epithelial phenotype to an endothelial phenotype, a process referred to aspseudovasculogenesis or vascular mimicry (upper panel). In preeclampsia, cytotrophoblasts fail to adopt an invasive endothelial phenotype. Instead, invasion of the spiral arteries is shallow, and they remain small-caliber resistance vessels (lower panel).  (From Lam C, Kim KH, Karumanchi SA: Circulating angiogenic factors in the pathogenesis and prediction of preeclampsia,Hypertension 46:1077–1085, 2005.)ABNORMAL PLACENTATIONFigure 1-3 During early pregnancy the tips of the maternal spiral arteries are occluded by invading endovascular trophoblast cells, impeding flow into the IVS. The combination of endovascular and interstitial trophoblast invasion is associated with physiologic conversion of the spiral arteries. Both processes are deficient in preeclampsia, and the retention of vascular smooth muscle may increase the risk of spontaneous vasoconstriction, and hence an ischemia-reperfusion type injury to the placentaConsequences of inadequate perfusion is intermittent hypoxia – generation of oxidative stressRelease of antiangiogenic proteins, activation of inflammation --- reduced organ perfusion in mother
  7. Neuro – seizure, headache, clonus (>3 beats)Eyes – Papilloedema, blurry vision, flashingCardiac – LV Failure due to increased afterloadLungs – ARDS – pulm edema; Starling’s Forces; increased pulm capillary hydrostatic pressure; reduced plasma oncotic pressure, endothelial dysfunctionAbdomen – pain below ribs, liver tenderness, vomitRenal – decreased urine output; damage to endothelium and glomeruliHeme – Platelets below 100 X109 per litreLiver – elevated AST/ALT above 70 iu/litreHELLP: characterized by hepatic infarctions and subcapsular hematoma leading to hepatic ruptureComputed tomography scan of the liver demonstrating hepatic infarct.Subcapsular hematoma in patient with HELLP syndrome.
  8. Side effects:Labetalol – can cause neonatal bradycardia, avoid in women w/asthma and heart failureHydralazine – can cause maternal hypotensionMethyldopa – is only a PO drug, central acting
  9. Cochrane Review:Physicians should use their own judgment on which drug to choose
  10. French recommendations: Society of anesthesiaCollege of GYN FranceSociety of Perinatal medicineSociety of neonatology
  11. Magnesium SulfateUse: prevention of eclamptic seizuresDoses:3.5 – 7 – therapeutic8-10 – areflexia13 – cardioresp arrestDosing: loading 4gram over 5 minutes, then 1 gram/hr for 24 hrsRecurrent seizures, give 2-4 grams over 5 minutesEffect treatment option for eclampsia – MOA is multifaceted encompassing both vascular and neurological mechanismMay act centrally to inhibit NMDA receptors providing anticonvulsant activity by increasing seizure thresholdCommittee Opinion piece as a reaction to the FDA changing drug classification A to Category D because of reports of fetal/neonate bone demineralization and fractures associated with long term utero use
  12. Magnesium SulfateUse: prevention of eclamptic seizuresDoses:3.5 – 7 – therapeutic8-10 – areflexia13 – cardioresp arrestDosing: loading 4gram over 5 minutes, then 1 gram/hr for 24 hrsRecurrent seizures, give 2-4 grams over 5 minutesEffect treatment option for eclampsia – MOA is multifaceted encompassing both vascular and neurological mechanismMay act centrally to inhibit NMDA receptors providing anticonvulsant activity by increasing seizure threshold