Acute hypertensive emergencies in pregnancy

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Acute hypertensive emergencies in pregnancy

• Critical Care Medicine
• 2005 Vol. 33, No 10 (Suppl.) Resident ???

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Hypertension

• One of the most common medical disorders
  affecting pregnancy
• Complicates 12 of pregnancies and responsible
  for 18 of maternal deaths in US
• Article focus Management of acute hypertensive
  crisis in pregnancy
• In obsterical practice, the level of BP elevation
  is used as a guide for diagnostic and management
  decisions

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• Hypertension in pregnancy
• systolic pressure ?140 mmHg or
• diastolic pressure ? 90 mmHg
• Hypertension before 20 wks gestation is
  indicative of chronic hypertension antedating the
  pregnancy and is usually essential (90)

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• Preeclampsia hypertension and proteinuria (gt
  300mg in a 24-hr specimen)
• Gestational hypertension hypertension without
  proteinuria or other signs or symptoms of
  preeclampsia
• Eclampsia occurrence of seizures or coma in the
  presence of preeclampsia or gestational
  hypertension

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• Hypertensive encephalopathy acute manifestation,
  may include seizure and coma and can occur in the
  pregnant woman with a lower BP than in the
  nonpregnant woman
• Eclampsia vs. hypertensive encephalopathy
• 10-yr review, only 3 cases of hypertensive
  encephalopathy found among 79,301 deliveries, 250
  cases of eclampsia

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Pathophysiology of hypertension in pregnancy
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• Not completely understood
• Angiotensin-aldosterone system is up-regulated in
  pregnancy, favoring BP increases
• Counterbalanced, by a 30 decrease in SVR that
  normally occurs early in pregnancy
• SVR reduction result in a decline in BP of 10 as
  early as 7 wks gestation and even more pronounced
  by midpregnancy

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• Pregnant women have significant increase in blood
  volume and cardiac output
• Mild preeclampsia SVR may be low, CO increased
• Severe preeclampsia high SVR/low cardiac output
  stage
• Brain preeclampsia may be accompanied by both
  underperfusion (low SVR), and overperfusion (high
  SVR), with subsequent risk of hypertensive
  encephalopathy
• Headache

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Acute Treatment of Severe Hypertension in
Pregnancy
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• Cut point systolic pressure of 160 mmHg or
  diastolic pressure of 105-110 mmHg (mild or
  severe)
• Mild uncomplicated chronic hypertension do not
  require treatment
• End-organ damage (nephropathy, LV hypertrophy,
  severe retinopathy) warrant antihypertensive
  therapy even at levels in mild range (lt 160/110
  mmHg)

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• No evidence of antihypertensive treatment reduces
  the incidence of fetal growth restriction,
  placental abruptio, or superimposed preeclampsia
  or improves perinatal outcomes
• A recent meta-analysis found that treated
  patients are more likely to have growth
  restricted infants in parallel with their
  reduction in mean arterial pressure, suggesting
  a negative impact of BP reduction on
  uteroplacental perfusion

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• the major indication for treatment of
  hypertension in pregnancy is for maternal benefit

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• Once a severe range of BP is reached,
  antihypertensive treatment should be initiated
  regardless of the type of hypertension involved
• Severe acute hypertension may be associated with
  end-organ complications such as myocardial
  infarction, stroke, renal failure, uteroplacental
  insufficiency, and placental abruption
• Persistent blood pressure 240/140 mm Hg
  identifies a genuine hypertensive emergency, ICU
  should be considered

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• The goal is to reduce diastolic pressure to just
  below 100 mmHg and not to attempt to normalize
  pressure because of the potential deleterious
  effect on the fetus

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Hydralazine

• Peripheral arteriolar vasodilator
• Drug used for gt45 yrs in the treatment of severe
  hypertension in pregnancy
• Onset of action is relatively slow (1020 mins)
• Common side effects (50) reflex tachycardia,
  hypotension, headaches, palpitations, flushing,
  anxiety, tremors, vomiting, epigastric pain, and
  fluid retention
• In the neonate, thrombocytopenia and a lupus-like
  syndrome have been reported after maternal use in
  third trimester

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• A recent meta-analysis concluded that hydralazine
  may not be the best first-line drug for treatment
  of severe hypertension in pregnancy
• Less effective than nifedipine, equally effective
  to labetalol, but associated with poorer maternal
  and perinatal outcomes
• More poorly tolerated than other antihypertensives

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Labetalol

• selective a1 (postsynaptic) and nonselective
  ß-blocker, with more ß effect than a , and
  probably the most commonly used agent for acute
  severe hypertension in pregnancy
• decreases SVR and slows the heart rate, reducing
  myocardial oxygen consumption
• does not influence renal function

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• The most frequent maternal side effects are
  dizziness, nausea, headaches, and fatigue
• Neonatal side effects may include hypotension,
  hypoglycemia, hypothermia, and bradycardia
• Contraindicated in patients with asthma

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• Reduces peripheral vascular resistance without
  reducing peripheral blood flow, and cerebral,
  renal, and coronary flows are unchanged
• Even after a significant reduction in maternal
  blood pressure and heart rate, labetalol does not
  affect the uteroplacental blood flow or fetal
  heart rate

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• The lack of reflex tachycardia, bradycardia,
  increased intracranial pressure, and the rare
  occurrence of significant hypotension make
  labetalol a good choice in patients with
  myocardial infarction, left ventricular or
  congestive heart failure, atrial fibrillation,
  cerebrovascular accidents, or hypertensive
  encephalopathy
• does not decrease cardiac output

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• contraindicated in patients with preexisting
  myocardial disease and decompensated cardiac
  failure
• Coadministration of a calcium channel blocker may
  increase the cardiodepressant effect of labetalol

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Atenolol

• cardioselective ß-blocker (acts on ß1 receptors
  more than ß2)
• associated with fetal growth restriction,
  especially after prolonged use in pregnancy
• should only be used when other similar agents are
  ineffective
• Experience with esmolol in pregnancy is very
  limited, and reports of fetal distress and
  neonatal bradycardia after esmolol
  administration? discouraged its use

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Calcium channel blockers

• act on arteriolar smooth muscle and induce
  vasodilation by blocking calcium entry into the
  cells
• Reduction in peripheral resistance decreases
  afterload
• The effect on the venous circulation is only
  minimal
• The maternal side effects include tachycardia,
  palpitations, headaches, facial flushing, and
  ankle edema through a local microvascular effect

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Nifedipine

• used over the last decade for both tocolysis and
  management of hypertension in pregnancy
• An unusual characteristic is that the higher the
  BP, the further it decreases after nifedipine
  administration

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• A small randomized trial of 50 pregnant women,
  oral nifedipine controls hypertension more
  rapidly than intravenous labetalol, as early as 1
  hr after the initial administration
• Acts as a selective renal arteriolar vasodilator
  and natriuretic, with a significant increase in
  urinary output

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• nifedipine increases cardiac index
• lowers BP without reducing uteroplacental blood
  flow and without significant fetal heart rate
  abnormalities

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• reports of unpredictable decreases in blood
  pressure
• As a result of this unfavorable publicity,
  short-acting nifedipine (capsules) was withdrawn
  from some national markets (Australia) as well as
  from many hospital pharmacies in the United States

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Nicardipine

• onset of action in 10 mins and results in
  adequate reduction of BP within 20 mins (duration
  of action 46 hrs)
• In a multiple-center placebo-controlled study,
  intravenous nicardipine was shown to be both
  effective and safe in patients with severe
  hypertension
• The most common adverse reaction was headaches

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• Nicardipine acts more selectively on the blood
  vessels than on the myocardium, with less reflex
  tachycardia
• It has been reported that nicardipine improves
  left ventricular activity and is less likely to
  cause cardiac ischemia

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• Isolated reports of the combination of nifedipine
  and magnesium sulfate causing neuromuscular
  blockade or severe hypotension, with maternal
  death ? not been observed in either observational
  or randomized trials
• Recent data would indicate that short-term
  treatment with calcium channel blockers such as
  nifedipine or nicardipine for severe hypertension
  in pregnancy is effective and safe

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Prazosin

• peripheral vasodilation
• without tachycardia or increased intracranial
  pressure
• beneficial metabolic effects of reducing plasma
  glucose and insulin levels, decreasing
  low-density lipoprotein cholesterol, and
  increasing high-density lipoprotein cholesterol
• block a1-receptors in both arterioles and veins ?
  resulting in a reduction in peripheral vascular
  resistance and decreased venous return
• Renal dysfunction does not affect elimination
  kinetics because the drugs are mainly metabolized
  by the liver

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• can be used in pregnant patients with congestive
  heart failure, diabetes, or asthma or in patients
  undergoing hemodialysis
• The most frequent maternal side effects include
  fluid retention, orthostatic hypotension,
  palpitations, nasal congestion, headaches,
  drowsiness, weakness, and nausea
• No adverse fetal effects are known

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Nitroprusside

• vasodilator that acts via the release of nitrous
  oxide to effect a potent reduction of both
  preload and afterload
• improves left ventricular function, leading to a
  reduction in pulmonary congestion and myocardial
  oxygen demand
• It is prudent to avoid nitroprusside in patients
  with raised intracranial pressure, left
  ventricular outflow obstruction, or hypothyroidism

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• rapid onset of action (within 30 secs)
• effect disappears within 3 mins after cessation
  of infusion
• Rebound hypertension may occur after abrupt
  discontinuation of the infusion necessitating the
  use of another antihypertensive agent on
  discontinuation

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• Known adverse effects include headache,
  dizziness, flushing, palpitations, and
  ototoxicity
• Cyanide toxicity has been reported, and is
  characterized by central nervous system
  dysfunction, cardiovascular instability, and
  lactic acidosis
• There are theoretical concerns about fetal
  cyanide toxicity ? unproven

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• Nitroprusside should be used in pregnancy only in
  complicated cases of severe hypertension,
  preferably after other agents have been
  ineffective
• The infusion should not be continued for more
  than several hours in a pregnant woman

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Nitroglycerin

• A relatively safe drug and may be more useful
  than nitroprusside for patients with pulmonary
  hypertension or myocardial ischemia
• may also be used in pregnant women with severe
  preeclampsia or chronic hypertension to blunt the
  hypertensive effects of intubation or extubation

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• Known side effects include headaches,
  hypotension, nausea, and vomiting
• Nitroglycerin is not an effective arterial
  vasodilator, and when used for hypertensive
  emergencies, not infrequently, additional drugs
  are needed
• At high-dose infusion there is also the risk of
  methemoglobinemia

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• In general, nitroglycerin is not the ideal
  first-line antihypertensive agent in pregnant
  women, with the exception of patients
  experiencing an acute coronary event

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Angiotensin-converting enzyme (ACE) inhibitors

• active against renin-dependent vasoconstriction,
  first line of treatment in nonpregnant patients
  with decompensated heart failure, acute pulmonary
  edema, or acute coronary ischemia
• Contraindicated in the second and third trimester
  of pregnancy because of the associated increase
  in fetal and neonatal morbidity and mortality
• Fetal toxic effects renal dysgenesis,
  oligohydramnios, calvarial hypoplasia, and fetal
  growth restriction

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• After fetal exposure, the neonate is at risk of
  developing renal failure and hypotension
• May be used postpartum, including in lactating
  mothers
• There may be cases of primary or secondary
  malignant hypertension in pregnancy refractory to
  other antihypertensive medication (as in
  scleroderma) that can be only controlled by ACE
  inhibitors ? ACEI is life-saving for the mother

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• In a review of 85 women taking ACE inhibitors
  during pregnancy, the perinatal mortality was
  almost 10, and the risk of persistent renal
  disease in the offspring was 41 with enalapril
  and 5 with captopril
• No risk estimates are available for the newer ACE
  inhibitor lisinopril, but a few reports suggest
  that lisinopril is similarly concerning

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Diuretics

• Patients with chronic hypertension, diuretics can
  markedly potentiate the response to
  antihypertensives
• An older meta-analysis showed no increase in
  adverse perinatal effects when diuretics were
  used in pregnancy for the management of
  hypertension

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• Indication hypertension in the setting of renal
  failure and congestive heart failure or pulmonary
  edema
• There is concern about their use in preeclampsia,
  characterized by blood volume restriction, and in
  chronic hypertensive women who may fail to expand
  their plasma volume appropriately in pregnancy
• Diuretics should not be used if reduced
  uteroplacental perfusion is suspected or in cases
  of fetal growth restriction

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• Diuretic therapy may lead to hyperuricemia,
  invalidating serum uric acid as diagnostic marker
  for preeclampsia
• Other side effects may be hypokalemia,
  hyperlipidemia, and hemorrhagic pancreatitis
• Spironolactone is not recommended during
  pregnancy owing to theoretical antiandrogenic
  effects on fetal sexual development

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