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- 2. Contents • Definition • Classification • Introduction • Therapy
- 3. Gestational hypertension Gestational hypertension •New onset of systolic blood pressure ≥140 mmHg or diastolic blood pressure ≥90 mmHg on at least 2 occasions 4 hours apart after 20 weeks of gestation in a previously normotensive individual •And: •No proteinuria •No severe features of preeclampsia (thrombocytopenia, renal insufficiency, elevated liver transaminases, pulmonary edema, cerebral or visual symptoms) New onset of systolic blood pressure ≥140 mmHg or diastolic blood pressure ≥90 mmHg
- 4. Chronic Hypertension Chronic (preexisting) hypertension •Hypertension diagnosed or present before pregnancy or before 20 weeks of gestation. Hypertension that is first diagnosed during pregnancy and persists for at least 12 weeks post-delivery is also considered chronic hypertension. • The blood pressure criteria are systolic blood pressure ≥140 mmHg, diastolic blood pressure ≥90 mmHg, or both. Ideally, this diagnosis is based on at least 2 elevated blood pressure measurements taken at least 4 hours apart. In the setting of severe hypertension, the diagnosis can be confirmed in a shorter interval to facilitate timely treatment. •diagnosed or present before pregnancy or before 20 weeks of gestation •diagnosed during pregnancy and persists for at least 12 weeks
- 5. Preeclampsia Preeclampsia •New onset of systolic blood pressure ≥140 mmHg or diastolic blood pressure ≥90 mmHg on at least 2 occasions at least 4 hours apart after 20 weeks of gestation in a previously normotensive individual or systolic blood pressure ≥160 mmHg or diastolic blood pressure ≥110 mmHg confirmed within a short interval (minutes) to facilitate timely antihypertensive therapy •And:Proteinuria (≥300 mg per 24-hour urine collection [or this amount extrapolated from a timed collection], or protein:creatinine ratio ≥0.3, or urine dipstick reading ≥2+ [if other quantitative methods are not available]) •Or, in the absence of proteinuria, new-onset hypertension with the new onset of any of the following:Thrombocytopenia (platelet count <100,000/microL) •Renal insufficiency (serum creatinine of >1.1 mg/dL [97 micromol/L] or a doubling of the serum creatinine concentration in the absence of other renal disease) •Impaired liver function as indicated by liver transaminase levels at least twice the normal concentration •Pulmonary edema •Persistent cerebral or visual symptoms Proteinuria (≥300 mg per 24- hour urine collection [or this amount extrapolated from a timed collection], or protein:creatinine ratio ≥0.3, or urine dipstick reading ≥2+
- 6. Chronic hypertension with superimposed preeclampsia / Eclampsia Eclampsia •In a patient with preeclampsia, generalized seizures that cannot be attributed to other causes Chronic hypertension with superimposed preeclampsia* •Any of these findings in a patient with chronic hypertension:A sudden increase in blood pressure that was previously well-controlled or an escalation of antihypertensive therapy to control blood pressure •New onset of proteinuria or sudden increase in proteinuria in a patient with known proteinuria before or early in pregnancy
- 7. Gestational Chronic Pre-eclampsia / Eclampsia Chronic hypertension with superimposed preeclampsia HDP
- 8. Classification • Mild – Systolic blood pressure 140 to 149 mmHg and/or diastolic blood pressure 90 to 99 mmHg • Moderate – Systolic blood pressure 150 to 159 mmHg and/or diastolic blood pressure 100 to 109 mmHg • Severe – Systolic blood pressure ≥160 and/or diastolic blood pressure ≥110 mmHg
- 9. INTRODUCTION • Hypertension (defined as systolic blood pressure ≥140 mmHg or diastolic blood pressure ≥90 mmHg), either pregnancy- related or chronic • severe (defined as systolic blood pressure ≥160 mmHg or diastolic blood pressure ≥110 mmHg),
- 10. Major Issues ● Establishing a diagnosis ● When to initiate treatment and what should be target blood pressure ● What drugs to be given ● Which drugs to be avoided
- 11. WHEN TO INITIATE All patients with severe hypertension Patients with non-severe hypertension (chronic or pregnancy-related)
- 13. ACUTE THERAPY OF SEVERE HYPERTENSION ACOG Labetalol Hydralazine Nifedipine (Immediate release)
- 14. Initial dose Follow-up L a b e t a l o l 20 mg IV gradually over 2 minutes. • Repeat BP measurement at 10-minute intervals: If BP remains above target level at 10 minutes, repeat with 20 – 80 mg • Cumulative maximum dose is 300 mg. A continuous IV infusion of 1 to 2 mg/ • Adjust dose within this range to achieve target blood pressure. • Cumulative maximum dose is 300 mg
- 15. Hydralazine 5 mg IV gradually over 1 to 2 minutes. •If BP remains above target level at 20 minutes, - 5 or 10 mg IV over 2 minutes •Cumulative maximum dose - 20 to 30 mg per treatment event.
- 16. Drug Onset of Action (minutes) Duration (hours) Labet alol 1 - 2 3 - 6 Fewer adverse effects. Avoided in • asthma, • Pre-existing myocardial disease, • decompensated cardiac function, • heart block and • bradycardia. Hydr alazi ne 10 - 30 2 -4 Higher dosage associated with maternal hypotension, headaches, and abnormal fetal heart rate tracings Nifed ipine (I.R) 5 - 10 3-5 Reflex tachycardia and headaches
- 17. Target blood pressure Reduction of mean arterial pressure by no more than 25 percent 2 hours achieve target blood pressures of 130 to 150 mmHg (S) and 80 to 100 mmHg (D)
- 19. Treatment of hypertension refractory to first- line acute therapy DRUG Dose Comments Nicardipine Initial dose: 5mg/hour Max: 15mg/hour 91 percent reached target blood pressure within 130 minutes Esmolol ID: 250 to 500 mcg/kg over one minute ->intravenous infusion at 25 to 50 mcg/kg per minute Used in pregnant patients to control sympathetic hyperactivity from thyroid storm Nitroglycerine Infusion - 5 mcg/minute -> gradually increased every 3-5 min to a max dose of 100 mcg/minute Option for hypertension ass. with pulmonary edema when intravenous diuretics are not effective. Nitroprusside 0.25 – 10 mcg/kg/minute (max 2mcg/kg/minute) Last resort
- 20. Treatment of hypertension refractory to first- line acute therapy DRUG Dose Comments Nicardipine Initial dose: 5mg/hour Max: 15mg/hour 91 percent reached target blood pressure within 130 minutes Esmolol ID: 250 to 500 mcg/kg over one minute ->intravenous infusion at 25 to 50 mcg/kg per minute Used in pregnant patients to control sympathetic hyperactivity from thyroid storm Nitroglycerine Infusion - 5 mcg/minute -> gradually increased every 3-5 min to a max dose of 100 mcg/minute Option for hypertension ass. with pulmonary edema when intravenous diuretics are not effective. Nitroprusside 0.25 – 10 mcg/kg/minute (max 2mcg/kg/minute) Last resort
- 21. ORAL MAINTENANCE THERAPY Drug Usual Dose Max Dose Comments Labetalol 200 to 800 mg in 2 divided doses 2400 mg Can cause bronchoconstriction Hydralazine 50 to 100 mg in 2 to 4 divided doses 200 mg Chronic doses associated with an increased risk for developing lupus. Methyldopa 250 to 1000 mg in 2 to 3 divided doses 3000 mg Sedation is a common side effect. • asthma, • chronic obstructive lung disease, • heart failure, • bradycardia, • heart block.
- 22. POSTPARTUM PATIENTS Normal changes Low/Normal -------Increase (peaks 3-6 days)
- 23. POSTPARTUM PATIENTS Severe Hypertension Non-severe Hypertension
- 24. POSTPARTUM PATIENTS Severe Hypertension Non-severe Hypertension Furosemide therapy (20 mg orally once or twice per day for five days) reduces the time until resolution of postpartum hypertension,
- 25. POSTPARTUM PATIENTS Severe Hypertension Non-severe Hypertension Target blood pressure
- 26. POSTPARTUM PATIENTS Severe Hypertension Non-severe Hypertension Target blood pressure Monitoring after discharge
- 27. POSTPARTUM PATIENTS Severe Hypertension Non-severe Hypertension Target blood pressure Monitoring after discharge Duration
- 28. Drug options during breastfeeding transfer into milk of Beta blockers Propranolol Metoprolol Labetalol less than 2 percent CCB Diltiazem Nifedipine Nicardipine Verapamil less than 2 percent ACE Captopril Enalapril Low levels newborns may be more susceptible to the hemodynamic effects such as hypotension,
- 29. Drug options during breastfeeding transfer into milk of Beta blockers Propranolol Metoprolol Labetalol less than 2 percent CCB Diltiazem Nifedipine Nicardipine Verapamil less than 2 percent ACE Captopril Enalapril Low levels newborns may be more susceptible to the hemodynamic effects such as hypotension, Diuretics HTZ <50 mg/day is considered safe for the
- 30. Drug options during breastfeeding transfer into milk of Beta blockers Propranolol Metoprolol Labetalol less than 2 percent CCB Diltiazem Nifedipine Nicardipine Verapamil less than 2 percent ACE Captopril Enalapril Low levels newborns may be more susceptible to the hemodynamic effects such as hypotension, Diuretics HTZ <50 mg/day is considered safe for the newborn
- 31. OVERVIEW OF ANTIHYPERTENSIVE DRUGS USED IN PREGNANCY All antihypertensive drugs cross the placenta.
- 32. OVERVIEW OF ANTIHYPERTENSIVE DRUGS USED IN PREGNANCY All antihypertensive drugs cross the placenta. Drug Comment Labetalol preferred drug in this class preserve uteroplacental blood flow to a greater extent than others Atenolol Propranolol Generally avoided Metoprolol Pindolol considered acceptable alternatives to labetalol • Clark JA, Zimmerman HJ, Tanner LA. Labetalol hepatotoxicity. Ann Intern Med. 1990 Aug 1;113(3):210-3 • Sibai BM. Chronic hypertension in pregnancy. Obstet Gynecol. 2002 Aug;100(2):369-77.
- 33. OVERVIEW OF ANTIHYPERTENSIVE DRUGS USED IN PREGNANCY Drug Comment Nifedipine most commonly used intermediate- or extended-release formulation preferred Nicardipine a good maternal and fetal safety profile continuous intravenous infusion if prompt treatment of severe hypertension Oral treatment can be initiated in patients with non-severe hypertension Amlodipine widely used sparse data on its use in pregnancy
- 34. OVERVIEW OF ANTIHYPERTENSIVE DRUGS USED IN PREGNANCY Drug Comment Methyldopa Widely used for decades Mild antihypertensive effect Slow onset of action (3-6 hours) Hydralazine been widely used for many years for treatment of acute severe hypertension in pregnancy hypotensive response to intravenous hydralazine is less predictable than that seen with labetalol orally -> reflex tachycardia and fluid retention unless combined with a beta blocker. Diuretics Volume overload
- 35. OVERVIEW OF ANTIHYPERTENSIVE DRUGS USED IN PREGNANCY Drug Comment Methyldopa Widely used for decades Mild antihypertensive effect Slow onset of action (3-6 hours) Hydralazine been widely used for many years for treatment of acute severe hypertension in pregnancy hypotensive response to intravenous hydralazine is less predictable than that seen with labetalol orally -> reflex tachycardia and fluid retention unless combined with a beta blocker. Diuretics Volume overload Clonidine
- 36. OVERVIEW OF ANTIHYPERTENSIVE DRUGS USED IN PREGNANCY Drug Comment Methyldopa Widely used for decades Mild antihypertensive effect Slow onset of action (3-6 hours) Hydralazine used for many years for treatment of acute severe hypertension in pregnancy hypotensive response to less predictable than that seen with labetalol orally -> reflex tachycardia unless combined with a beta blocker. Diuretics Volume overload Clonidine effective in non-severe hypertension in pregnancy but may cause possibility of rebound hypertension
- 37. DRUGS TO AVOID IN PREGNANCY Drug Comment Atenolol Ass.with lower placental and fetal weight when used early in pregnancy Propranolol may promote uterine irritability ACE/ARBS/Renin inhibitors associated with significant fetal renal abnormalities when fetal exposure has been in the latter half of pregnancy Nitroprusside possibility of fetal cyanide poisoning Mineralocorticoid receptor antagonists anti-androgenic activity is a concern, particularly in male fetuses. Lydakis C, Lip GY, Beevers M, Beevers DG. Atenolol and fetal growth in pregnancies complicated by hypertension. Am J Hypertens. 1999 Jun;12(6):541- 7 Cooper WO, Hernandez-Diaz S, Arbogast PG, Dudley JA, Dyer S, Gideon PS, Hall K, Ray WA. Major congenital malformations after first-trimester exposure to ACE inhibitors. N Engl J Med. 2006 Jun 8;354(23):2443-51
- 38. Treatment of severe hypertension in pregnancy • Prompt treatment (within 30 to 60 minutes of diagnosis)
- 39. Treatment of severe hypertension in pregnancy • Drugs • Labetalol • Nicardipine • Hydralazine • Nifedipine Prompt treatment Aim: to reduce mean arterial pressure by no more than 25 percent over two hours I/V Oral
- 40. Treatment of non-severe hypertension in pregnancy Pregnant patients with chronic non-severe hypertension Pregnant patients with new-onset hypertension after 20 weeks of gestation • Target blood pressure – <135/85 mmHg • Drugs • Labetalol • Nifedipine • Methyldopa • Hydralazine • Drugs C/I • ACE • ARB • Renin Inhibitors
- 42. Postpartum hypertension • Postpartum follow-up – • Blood pressure 72 hours of discharge (severe hypertension during pregnancy or the postpartum period) • no later than 7 to 10 days postpartum (non-severe hypertension) • Discontinuing antihypertensive therapy • After approximately three weeks • Long-term prognosis
- 43. End….
- 44. References • ACOG Guidelines • NICE Guidelines • AHA Guidelines
Editor's Notes
- as soon as reasonably possible (30-60 minutes)
- We consider initiation of treatment at even lower blood pressure levels in antepartum adolescents and other patients whose baseline blood pressures were low (less than 90/75 mmHg) and in patients with signs of cardiac decompensation or cerebral symptoms (eg, headache, visual disturbances, chest discomfort, shortness of breath, confusion), but we acknowledge that this approach is not evidence based. If blood pressure increases in a short time, symptoms (particularly headache) may occur even in young patients with pressures <150/100 mmHg.
- ugh the more common approach in the United States is to only begin antihypertensive treatment of gestational hypertension and preeclampsia when blood pressure is severely elevated (systolic blood pressure ≥160 mmHg and/or diastolic blood pressure ≥110 mmHg) [6], in an analysis of 24 patients with stroke related to preeclampsia, 4 percent had systolic blood pressures below severe levels (ie, >155 mmHg and <160 mmHg), which supports our lower threshold for initiating therapy [20]. In patients with preeclampsia, there is evidence that the pathophysiology of the neurologic manifestations of eclampsia is similar to that of the posterior reversible encephalopathy syndrome [21]. If this is the case, then patients with preeclampsia may be more susceptible to the neurologic features of severe disease at lower blood pressures (eg, ≥150 rather than ≥160 mmHg systolic), and this would support beginning antihypertensive therapy at a lower threshold in these patients
- the choice of antihypertensive should depend on the clinician's experience and familiarity with a particular drug with consideration of its adverse effects and patient preferences, nimodipine, diazoxide, and ketanserin (no longer actively marketed worldwide) were probably best avoided [22].
- The fall in blood pressure begins within 5 to 10 minutes and lasts from three to six hours. If labetalol alone is ineffective, we suggest switching to hydralazine. Alternatively, intravenous nicardipine or oral nifedipine can be used.
- The fall in blood pressure begins within 10 to 30 minutes and lasts from two to four hours. Adequate reduction of blood pressure is less predictable than with IV labetalol. f a total cumulative dose of 20 to 30 mg per treatment event does not achieve optimal blood pressure control or heart rate exceeds 100 beats/minute, another agent should be used.
- Tachycardia is less common with
- aggressively lowering blood pressure (eg, <120/80) in such cases as this may be associated with decreased uteroplacental perfusion.
- Esmolol ; titrate incrementally up to a maximum of 300 mcg/kg per minute. No studies have described use of esmolol for treatment of preeclampsia, but it has been used in pregnant patients to control sympathetic hyperactivity from thyroid storm NTG option for hypertension ass. with pulmonary edema when intravenous diuretics are not effective.
- magnesium sulfate, which is usually administered to patients with preeclampsia, eclampsia, or gestational hypertension with severe features, is never a substitute for prompt initiation of antihypertensive treatment of severe hypertension as it has minimal effects on blood pressure.
- Oral antihypertensive therapy may be needed to maintain blood pressure in the target range in patients in whom antihypertensive therapy was initiated and delivery is not imminent. There is no consensus on the optimum target blood pressure range for these patients. Targets of 110 to 140/85, ≤135/85, <140/90, and 130 to 140/80 to 90 mmHg have been suggested and are reasonable Methyldopa is also acceptable, but many patients will not achieve blood pressure goals or are bothered by its sedative effect at high doses
- significantly higher in the immediate postpartum period than antepartum or intrapartum.
- he majority of pregnancy-related strokes occur in the first 10 days after delivery [50] and typically within 48 hours postpartum, with hypertension the strongest risk factor [49]. One guideline suggests avoiding methyldopa postpartum because of the risk of postnatal depression We use antihypertensive medications similar to those used for maintenance therapy in pregnancy since most obstetric providers are familiar with these medications and they are compatible with breastfeeding
- Brief furosemide therapy (20 mg orally once or twice per day for five days) can reduce the time until resolution of postpartum hypertension, especially if hypertension is accompanied by severe edem Some data
- <135/85 In patients on antihypertensive therapy, systolic blood pressures ≥140 mmHg or diastolic blood pressures ≥90 mmHg in the 12 hours before discharge were associated with a three-fold increase in risk for readmission because of hypertensive complications, in one study
- 72 hours of discharge for patients with severe hypertension during pregnancy or the postpartum period and no later than 7 to 10 days postpartum for patients with nonsevere hypertension
- may develop hypotension as their blood pressure returns to the normal baseline level. , it is reasonable to stop the antihypertensive drug after approximately three weeks and monitor blood pressure to assess whether further treatment is indicated.
- None have been associated with adverse events in infants. By contrast, atenolol and acebutolol are more extensively excreted into breast milk, and beta blockade in nursing infants has been reported ACE we suggest that the hemodynamic status of the infant be considered when deciding whether patients taking these drugs should breastfeed.
- There is no information on use of angiotensin II receptor blockers (ARBs) during breastfeeding. Intense diuresis from a loop diuretic may decrease milk production when lactation is being established, but low doses with more gradual diuresis are less of a concern. The effects of loop diuretics on established lactation have not been studied.
- Methyldopa and hydralazine – Both of these drugs appear to be safe for the newborn. Because maternal depression has been reported following methyldopa administration and postpartum patients are already at risk for postpartum depression, ACOG suggests avoiding use of methyldopa in postpartum patients [6].
- here are limited data from large well-designed randomized trials on which to base a strong recommendation for use of one drug over another
- Labetalol has been associated with maternal hepatotoxicity, which, although rare, is important to recognize as it may be confused with the elevated liver chemistries of preeclampsia with severe features and HELLP syndrome.
- widely available in immediate-release (rapid- acting) and extended-release formulations. he rate of fetal morphologic abnormalities was similar in the three groups (range 4.2 to 5.6 percent), suggesting that amlodipine may not be associated with an increased risk of malformations.
- widely used in pregnant patients for several decades and its long-term safety for the fetus has been more extensively documented than other antihypertensive agents Many patients will not achieve blood pressure goals on this oral agent or are bothered by its sedative effect at high doses. Although methyldopa is not widely used outside of pregnancy, it remains useful in this setting, particularly in patients who develop adverse effects or are intolerant of other, more widely used medications.
- Diuretics ompensatory stimulation of the renin angiotensin system occurs and plasma volume increases, although usually not back to baseline. Loop diuretics are the preferred approach to treatment of heart failure with pulmonary congestion during pregnancy.
- he author has prescribed clonidine for rare patients in whom methyldopa, labetalol, and nifedipine could not be used. Because clonidine is available as a transdermal patch, it is particularly useful for patients who cannot take an oral antihypertensive drug.
- They may promote uterine irritability since myometrial relaxation of the gravid uterus is a beta-2-adrenergic receptor-mediated process (beta-adrenergic receptor agonists are used for tocolysis).
- Prompt treatment (within 30 to 60 minutes of diagnosis) to achieve initial target blood pressures in the range of 130 to 150 mmHg systolic and 80 to 100 mmHg diastolic.
- more favorable pregnancy outcomes (reduction in preeclampsia with severe features, medically indicated preterm birth <35 weeks, abruption, or fetal or neonatal death) without increasing the frequency of small for gestational age birth weight.
- Blood pressure peaks three to six days postpartum.
- Blood pressure peaks three to six days postpartum. If prepregnancy blood pressure was normal and the patient is normotensive on medication after delivery increased risk for developing chronic hypertension and other manifestations of cardiovascular disease raditional cardiovascular risk factors, including hyperlipidemia, diabetes, obesity, and sedentary lifestyle, should also be addressed.