Hypertension is seen in about 10 per cent of all pregnancies. It is the most comnloii medical complication of pregnancy and a major cause of both fetal and maternal mortality, the most serious problems being associated with pre-eclampsia and eclampsia. In general, hypertension in pregnancy is defined as blood pressure greater than 140 inm Hg systolic and 90 mm Hg diastolic in at least two occasions six hours apart.
a) Classification: (Joint National Committee - 7th report. JNC7)
1) Chronic hypertension
BP 140 mm Hg systolic and 90 inln Hg diastolic prior to pregnancy or before 20 weeks of gestation. Persists > 12 weeks post partum.
2) Pre eclampsia
BP 140 mm Hg systolic and 90 mm Hg diastolic wit11 proteinurias 100 mg/24 hours,after 20 weeks of gestation, can progress to eclampsia (seizures). More common in nulliparous women multiple gestations,'coin~non with hypertension 4 years, family
history of pre-eclampsia, hypertension in previous pregnancy and renal disease.
3) Chronic hypertension with New onset of proteinuria after 20 weeks in a superimposed pre-eclmpsia WOIWM with hypertension, sudden 2 to 3 fold increase in proteinuria, sudden increase in BP,thrombocytopenia, elevated alanine aminotransferase or aspqate
aminotransferase.
4) Gestational hypertension
alncludl Hypertensiori without proteinuria 20 weeks after gestation. Te~nporruy diagnosis:it may be proteinuric phase of pre-eclampsia or recurrence of chronic hypertension abated inn mid pregnancy, may evolve to pre-eclampsia.If severe, may result in higher rates of delivery and growth retardation than mild pre-eclampsia.
5) Transient hypertension
Retrospective diagnosis
Blood pressure normalizes by 12 weeks post partum, may recur in subsequent pregnancies,predictive of future primary hypertension.
b) Pre-pregnancy Assessment and Management of Individual Types Women should be evaluated prior to conception to define their blood pressure status.If liypertension is present, its severity is assessed and possible secondary causes should be looked into. Target organ damagc is evaluated and the blood pressure is treated. Pheochromocytoma in particular need to be screened, because this is associated with high morbidity and mortality in pregnancy. If a hypertensive woman plans conception, it is prudent to change over to medication known to be safc in pregnancy, such as methyl dopa or beta-blockers. Angiotensin Converting Enzyme Inhibitors (ACEI) or Angiotensin I1 Receptor Blockers (ARB) should be discontinued prior to attempt to conception or as soon as pregnancy is confirmed. Renal parameters to be evaluated as moderate to severe renal insufficiency in pregnancy may accelerate both hypertension and underlying disease and markedly reduce fetal survival.
Pre-eclampsia and Eclampsia: (Table ) This is characteiized by proteinuria, hypertension, edema and at times abnoimality in liver functiori or coagulation or both,may progress to "eclampsia - life threatening event". The eclampsic fit may be preceded by headache, visual disturbances, hyper reflexia, epigastric pain, but may occur suddenly without any warning in asymptomatic women ('eclampsia' means 'lightning'). The ominus signs are - BP > 160/110. Proteinuiia of > 2 G in 24 hours,increasing serum creatinine levels low platelet count, upper abdomiiial pain, visual disturbances, cardiac decompensation (pulmonary edema), retinal hemorrhage.HELLP Syndrome: It is a variant of pre-eclampsia, can occur as deceptively benign with minimal or no rise of blood pressure, decreased platelets count, elevation in liver enzymes. This form may progress rapidly to life threatening symptoms, characteiized by hemolysis, marked abnormality of liver function and coagulation. This is termed HELLP Syindrome (Hemolysis, Elevated liver enzymes and Low Platelet count) - is an emergency and requires prompt termination of pregnancy.
Pathophysiology: The exact pathophysiologic mechanism is not clearly understood.It is considered as a disorder of endothelial dysfunction with vasospasm. Abnormal placental development or placental damage from diffuse microthrombosis may be central to the development of pre-eclampsia. Altered maternal immune response to fetallplacental tissue may contribute to the development of pre eclampsia. Endothelial damage leads to pathologic capillary leak. Decreased utero-placental blood flow can lead to fetal growth restriction. Hypei-tension in pre-eclampsia is due to vasospasm and there is evidence of hyper responsiveness to vasoactive peptides like angiotensin II and epinephrine.
Preventive Measures
1) Low dose aspirin 60-80 mg daily starting early after 12'" week of gestation has been suggested. Low dose aspirin primarily inhibit platelet thromboxane, sparing endothelial cell prostacyclin production, preventing both intravascular clotting and vasoconstriction.Its benefit has not been established in low iisk group.Aspirin may cause excessive bleeding during delivery.
2) Supplemental calcium given to pregnant women has been shown to reduce theincidence of hypeqension:Treatment: Hospitalization is indicated for bed rest, control of blood pressure,seizure prophylaxis in the presence of signs of inlpending eclampsia, and timely delivery. Many women with pre-eclampsia have previously been normotensive acute BP elevations even to modest levels (1501100 minHg) may cause significant symptomatology and require treatment. Trcatrnent does not alter the underlying pathophysiology of the disease, but it may slow its progression and provide time for fetal maturation. Pre-eclampsia rarely remits spontaneously and in most cases worsens with time. Delivery is the appropriate therapy for the mother; it may' compromise a fetus 01 less than 32 weeks gestation. Regardless of gesta~ional age, delivery should be strongly considered when there are signs of fetal distress or iljtrauterine growth retardation or signs of maternal problems including severe h)pertensioll, hemolysis, elevated liver enzymes, low platelet count; deteriorating renal function, visual disturbances, head ache or epigastric pain. Vaginal delivery is preferable to caesarian delivery to avoid the added stress of surgery.
Drugs
1) Iiydralazilze: 5 mg IV bolus, then 10 mg every 20-30 minutes to a ir~aximun~of 25 mg. Repeat in sevcral hours if necessary.
2) Labet(i1ol: (Second Line) 20 ing IV bolus, then 40 mg'l0 ~ninutes later; 80 mg every 10 minutes for 2 additiollal doses to a ~naxinluin of' 220 mg.
3) Nifedipine: (Contsoversial) 10 mg per oral, repeat every 20 minutes to a maximum of 30 rng. Caution whcn using nifedipine with magnesium sulfate; call cause precipitous drop in blood pressure. Short acting nifedipine is not approved by US-FDA for managenlent of mypertension.
4) Soclizun Nitro Prusside: (rarely used when others fail) 0.25 pglkglmin for a maxiinum of 5 yglkglinin. Fetal cyanide poisoning may occur if used for more than four hours.For control of convulsions magnesiun~ sulfate is the choice of therapy. Phenytoin may also be used.
Treatment of Chrolzic Hypertension during Pregnancy: Women with stage one hypertension are at low, risk for cardiovascular coinl~lications during pregnancy and are candidates for life style inodification therapy, as there is no evidence that pharmacological treatment improves neonatal outcomes. Also, blood pressure usually falls during the first half of pregnancy, therefore hypeilension may bc easier to contsol with reduced or no medication. In life style modification, aerobic exercises should be rest icted on the
basis of concerns that inadequate placental blood flow may increase the risk of pre-eclampsia, and weight reduction should not be attempted even in obese pregnant women.Restriction of sodium intake to be restricted to 2 g, recommended for those with primary hypertension. Use of alcohol and tobacco must be slrongly discouraged.The use of anti-hypertensive agents in pregnant wonlen varies among centers; some prefer to stop using antihypertensive medications while maintaining close observation including use of hoine BP monitoring. This approach reflects the concern about the safety of drug tieatment in pregnancy. A meta-analysis of drug treatment for stage one and stage two hypertension in pregnancy showed a duect relation between treatment induced fall of arterial pressure and the proportion of small for gestational age infants.
1) Methyl Dopa: Centrally acting agent. First line of drug in treatment of hypertension during pregnancy. Dose 250 mg orally twice or thrice a day, not to exceed 3 G/day. Ide effects- somolesense, dryness of mouth. Caution in liver disease.. Contraindicated in documented hypersensitivity, acute liver disease.
.
2) Labetalol: Preferred drug in pregnancy. It is a combined beta and alpha blocking agent. Not associated with fetal growth retardation (unlike other beta-blockers).Used alternatively to hydralazine in pre-eclampsia/eclampsia. Dose 100 mg twice a day. Contraindicated in documented hypersensitivity, bradycardia,atrioventricular blocks reactive airway disease.
3) Other Beta-blockers:
a) Metoprolol : 50 to 100 mg orally. Second line agent.
b) Atenolol : 50 to 100 mg orally.
May cause intrauterine growth restriction. May cause brady arrhythmias.
4)Calcium Channel Antagonists: Limited data for use in pregnancy. Nifedipine - 10 to 30 mg orally. Also used as a tocolytic agent in pregnancy. Other agents in this group are arnlodipine, verapamil, diltiazem.
5 ) Clonidin: Used as a third line agent. Limited data of its use in pregnancy. It is a centrally acting drug. Dose 0.2-1.2 mglday orally. Abrupt discontinuatioll may lead to rebound hypertension. Caution in renal impartment.
6) Diuretics:
w Thiazides : Not commonly used to treat hypertension in pregnancy. Inhibit-absorption of sodium in distal tubules causing increased excretion of sodium and water as well as potassium,
.
Hydrochlorothiazide : 25 to 100 mg orally. May prevent normal physiologic volume expansion that occurs in pregnancy and may reduce uterine flow. Its use may be restricted to women with volume loaded states, e.g., renal or. cardiac disease.
w Furosernide : Not commonly used to treat hypertension in pregnancy, but used to tteat pulmonary edema associated with pre-eclampsia.
7) Hydralazine: IV is useful in treating severe hypertension due to pre-eclampsia1 eclampsia. Dose 10-20 mg IV. Caution in patients suspected coronary artery disease.
8) Other Drugs
a) Magnesium sulfate: 4-5 G IV followed by 2-3 Gthr. Used in women with eclampsia or severe pre-eclampsia. It is superior to phenytoin for preventing and treating eclampsic seizures.
a) Classification: (Joint National Committee - 7th report. JNC7)
1) Chronic hypertension
BP 140 mm Hg systolic and 90 inln Hg diastolic prior to pregnancy or before 20 weeks of gestation. Persists > 12 weeks post partum.
2) Pre eclampsia
BP 140 mm Hg systolic and 90 mm Hg diastolic wit11 proteinurias 100 mg/24 hours,after 20 weeks of gestation, can progress to eclampsia (seizures). More common in nulliparous women multiple gestations,'coin~non with hypertension 4 years, family
history of pre-eclampsia, hypertension in previous pregnancy and renal disease.
3) Chronic hypertension with New onset of proteinuria after 20 weeks in a superimposed pre-eclmpsia WOIWM with hypertension, sudden 2 to 3 fold increase in proteinuria, sudden increase in BP,thrombocytopenia, elevated alanine aminotransferase or aspqate
aminotransferase.
4) Gestational hypertension
alncludl Hypertensiori without proteinuria 20 weeks after gestation. Te~nporruy diagnosis:it may be proteinuric phase of pre-eclampsia or recurrence of chronic hypertension abated inn mid pregnancy, may evolve to pre-eclampsia.If severe, may result in higher rates of delivery and growth retardation than mild pre-eclampsia.
5) Transient hypertension
Retrospective diagnosis
Blood pressure normalizes by 12 weeks post partum, may recur in subsequent pregnancies,predictive of future primary hypertension.
b) Pre-pregnancy Assessment and Management of Individual Types Women should be evaluated prior to conception to define their blood pressure status.If liypertension is present, its severity is assessed and possible secondary causes should be looked into. Target organ damagc is evaluated and the blood pressure is treated. Pheochromocytoma in particular need to be screened, because this is associated with high morbidity and mortality in pregnancy. If a hypertensive woman plans conception, it is prudent to change over to medication known to be safc in pregnancy, such as methyl dopa or beta-blockers. Angiotensin Converting Enzyme Inhibitors (ACEI) or Angiotensin I1 Receptor Blockers (ARB) should be discontinued prior to attempt to conception or as soon as pregnancy is confirmed. Renal parameters to be evaluated as moderate to severe renal insufficiency in pregnancy may accelerate both hypertension and underlying disease and markedly reduce fetal survival.
Pre-eclampsia and Eclampsia: (Table ) This is characteiized by proteinuria, hypertension, edema and at times abnoimality in liver functiori or coagulation or both,may progress to "eclampsia - life threatening event". The eclampsic fit may be preceded by headache, visual disturbances, hyper reflexia, epigastric pain, but may occur suddenly without any warning in asymptomatic women ('eclampsia' means 'lightning'). The ominus signs are - BP > 160/110. Proteinuiia of > 2 G in 24 hours,increasing serum creatinine levels low platelet count, upper abdomiiial pain, visual disturbances, cardiac decompensation (pulmonary edema), retinal hemorrhage.HELLP Syndrome: It is a variant of pre-eclampsia, can occur as deceptively benign with minimal or no rise of blood pressure, decreased platelets count, elevation in liver enzymes. This form may progress rapidly to life threatening symptoms, characteiized by hemolysis, marked abnormality of liver function and coagulation. This is termed HELLP Syindrome (Hemolysis, Elevated liver enzymes and Low Platelet count) - is an emergency and requires prompt termination of pregnancy.
Pathophysiology: The exact pathophysiologic mechanism is not clearly understood.It is considered as a disorder of endothelial dysfunction with vasospasm. Abnormal placental development or placental damage from diffuse microthrombosis may be central to the development of pre-eclampsia. Altered maternal immune response to fetallplacental tissue may contribute to the development of pre eclampsia. Endothelial damage leads to pathologic capillary leak. Decreased utero-placental blood flow can lead to fetal growth restriction. Hypei-tension in pre-eclampsia is due to vasospasm and there is evidence of hyper responsiveness to vasoactive peptides like angiotensin II and epinephrine.
Preventive Measures
1) Low dose aspirin 60-80 mg daily starting early after 12'" week of gestation has been suggested. Low dose aspirin primarily inhibit platelet thromboxane, sparing endothelial cell prostacyclin production, preventing both intravascular clotting and vasoconstriction.Its benefit has not been established in low iisk group.Aspirin may cause excessive bleeding during delivery.
2) Supplemental calcium given to pregnant women has been shown to reduce theincidence of hypeqension:Treatment: Hospitalization is indicated for bed rest, control of blood pressure,seizure prophylaxis in the presence of signs of inlpending eclampsia, and timely delivery. Many women with pre-eclampsia have previously been normotensive acute BP elevations even to modest levels (1501100 minHg) may cause significant symptomatology and require treatment. Trcatrnent does not alter the underlying pathophysiology of the disease, but it may slow its progression and provide time for fetal maturation. Pre-eclampsia rarely remits spontaneously and in most cases worsens with time. Delivery is the appropriate therapy for the mother; it may' compromise a fetus 01 less than 32 weeks gestation. Regardless of gesta~ional age, delivery should be strongly considered when there are signs of fetal distress or iljtrauterine growth retardation or signs of maternal problems including severe h)pertensioll, hemolysis, elevated liver enzymes, low platelet count; deteriorating renal function, visual disturbances, head ache or epigastric pain. Vaginal delivery is preferable to caesarian delivery to avoid the added stress of surgery.
Drugs
1) Iiydralazilze: 5 mg IV bolus, then 10 mg every 20-30 minutes to a ir~aximun~of 25 mg. Repeat in sevcral hours if necessary.
2) Labet(i1ol: (Second Line) 20 ing IV bolus, then 40 mg'l0 ~ninutes later; 80 mg every 10 minutes for 2 additiollal doses to a ~naxinluin of' 220 mg.
3) Nifedipine: (Contsoversial) 10 mg per oral, repeat every 20 minutes to a maximum of 30 rng. Caution whcn using nifedipine with magnesium sulfate; call cause precipitous drop in blood pressure. Short acting nifedipine is not approved by US-FDA for managenlent of mypertension.
4) Soclizun Nitro Prusside: (rarely used when others fail) 0.25 pglkglmin for a maxiinum of 5 yglkglinin. Fetal cyanide poisoning may occur if used for more than four hours.For control of convulsions magnesiun~ sulfate is the choice of therapy. Phenytoin may also be used.
Treatment of Chrolzic Hypertension during Pregnancy: Women with stage one hypertension are at low, risk for cardiovascular coinl~lications during pregnancy and are candidates for life style inodification therapy, as there is no evidence that pharmacological treatment improves neonatal outcomes. Also, blood pressure usually falls during the first half of pregnancy, therefore hypeilension may bc easier to contsol with reduced or no medication. In life style modification, aerobic exercises should be rest icted on the
basis of concerns that inadequate placental blood flow may increase the risk of pre-eclampsia, and weight reduction should not be attempted even in obese pregnant women.Restriction of sodium intake to be restricted to 2 g, recommended for those with primary hypertension. Use of alcohol and tobacco must be slrongly discouraged.The use of anti-hypertensive agents in pregnant wonlen varies among centers; some prefer to stop using antihypertensive medications while maintaining close observation including use of hoine BP monitoring. This approach reflects the concern about the safety of drug tieatment in pregnancy. A meta-analysis of drug treatment for stage one and stage two hypertension in pregnancy showed a duect relation between treatment induced fall of arterial pressure and the proportion of small for gestational age infants.
1) Methyl Dopa: Centrally acting agent. First line of drug in treatment of hypertension during pregnancy. Dose 250 mg orally twice or thrice a day, not to exceed 3 G/day. Ide effects- somolesense, dryness of mouth. Caution in liver disease.. Contraindicated in documented hypersensitivity, acute liver disease.
.
2) Labetalol: Preferred drug in pregnancy. It is a combined beta and alpha blocking agent. Not associated with fetal growth retardation (unlike other beta-blockers).Used alternatively to hydralazine in pre-eclampsia/eclampsia. Dose 100 mg twice a day. Contraindicated in documented hypersensitivity, bradycardia,atrioventricular blocks reactive airway disease.
3) Other Beta-blockers:
a) Metoprolol : 50 to 100 mg orally. Second line agent.
b) Atenolol : 50 to 100 mg orally.
May cause intrauterine growth restriction. May cause brady arrhythmias.
4)Calcium Channel Antagonists: Limited data for use in pregnancy. Nifedipine - 10 to 30 mg orally. Also used as a tocolytic agent in pregnancy. Other agents in this group are arnlodipine, verapamil, diltiazem.
5 ) Clonidin: Used as a third line agent. Limited data of its use in pregnancy. It is a centrally acting drug. Dose 0.2-1.2 mglday orally. Abrupt discontinuatioll may lead to rebound hypertension. Caution in renal impartment.
6) Diuretics:
w Thiazides : Not commonly used to treat hypertension in pregnancy. Inhibit-absorption of sodium in distal tubules causing increased excretion of sodium and water as well as potassium,
.
Hydrochlorothiazide : 25 to 100 mg orally. May prevent normal physiologic volume expansion that occurs in pregnancy and may reduce uterine flow. Its use may be restricted to women with volume loaded states, e.g., renal or. cardiac disease.
w Furosernide : Not commonly used to treat hypertension in pregnancy, but used to tteat pulmonary edema associated with pre-eclampsia.
7) Hydralazine: IV is useful in treating severe hypertension due to pre-eclampsia1 eclampsia. Dose 10-20 mg IV. Caution in patients suspected coronary artery disease.
8) Other Drugs
a) Magnesium sulfate: 4-5 G IV followed by 2-3 Gthr. Used in women with eclampsia or severe pre-eclampsia. It is superior to phenytoin for preventing and treating eclampsic seizures.
b) Phenytoin: 500-1000 mg IV over one hour amd then 10 hours later, 500 mg orally. Less effective than magnesium in preventing eclarnpsic seizures but may be used if renal failure is present.
9) Angiotensin Converting Enzyme Inhibitors (ACEI) and Angiotensiil I1 Receptor r lockers (ARB) are contra indicated in pregnancy as they can cause fetal toxicity and dcath.
Anti-hypertensive Drugs During acta at ion: Usually breastfeeding is not contra indicated in hypertensive mothers. However all anti-hypertensive agents are excreted into the milk and hence in mothers with stage I hypertensipn, who wish to breast feed, it is better to with hold anti-hypertensive medication, with close monitoring of BP and to reinstitute the medications following discontinuation of nursing. No adverse effects are reported with methyl dopa. Labetalol and propranolol may be preferred if beta-blockcrs are indicated. ARB group of drugs should be avoided. Diuretics may reduce milk volume and there by suppress lactation.
Recurrence of Hypertension: In about 20 per cent to 50 per cent of subsequent pregnancies,hypertension recurs. Early onset of hypertension duiing first pregnancy, history of chronic hypertension and persistent hypertension beyond five weeks of post partum are the risk factors for recurrence of hypertension. Women with pre-eclampsia have a greater tendency to develop hypertension than those wit11 noimotensive pregnancies.
9) Angiotensin Converting Enzyme Inhibitors (ACEI) and Angiotensiil I1 Receptor r lockers (ARB) are contra indicated in pregnancy as they can cause fetal toxicity and dcath.
Anti-hypertensive Drugs During acta at ion: Usually breastfeeding is not contra indicated in hypertensive mothers. However all anti-hypertensive agents are excreted into the milk and hence in mothers with stage I hypertensipn, who wish to breast feed, it is better to with hold anti-hypertensive medication, with close monitoring of BP and to reinstitute the medications following discontinuation of nursing. No adverse effects are reported with methyl dopa. Labetalol and propranolol may be preferred if beta-blockcrs are indicated. ARB group of drugs should be avoided. Diuretics may reduce milk volume and there by suppress lactation.
Recurrence of Hypertension: In about 20 per cent to 50 per cent of subsequent pregnancies,hypertension recurs. Early onset of hypertension duiing first pregnancy, history of chronic hypertension and persistent hypertension beyond five weeks of post partum are the risk factors for recurrence of hypertension. Women with pre-eclampsia have a greater tendency to develop hypertension than those wit11 noimotensive pregnancies.
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