Comparison of labetalol and dihydralazine in hypertensive emergencies of pregnancy. Short-term treatment of severe hypertension of pregnancy: prospective comparison of nicardipine and labetalol. Dihydralazine or ketanserin for severe hypertension in pregnancy? Preliminary results. Intravenous labetalol and intravenous diazoxide in severe hypertension complicating pregnancy. [Management of severe pre-eclampsia/eclampsia. Comparison between nifedipine and hydralazine as antihypertensive agents]. [Efficacy of isosorbide in aerosol form in the management of hypertensive crisis in severe preeclampsia]. Nifedipine or hydralazine as a first-line agent to control hypertension in severe preeclampsia. Treatment of hypertension in patients with pre-eclampsia: a prospective parallel-group study comparing dihydralazine with urapidil. Nifedipine in acute hypertensive emergencies in pregnancy. Maternal and fetal haemodynamics in hypertensive pregnancies during maternal treatment with intravenous hydralazine or labetalol. A comparison of magnesium sulfate and nimodipine for the prevention of eclampsia. Ketanserin versus dihydralazine in the management of severe early-onset preeclampsia: maternal outcome. A comparative trial of labetalol and hydralazine in the acute management of severe hypertension complicating pregnancy. A comparative study of the use of epoprostenol and dihydralazine in severe hypertension in pregnancy. Ketanserin and hydralazine in hypertension in pregnancy--a randomised double-blind trial.
Labetalol (Trandate; Allen & Hanburys), a combined alpha- and beta-adrenergic blocking agent, was compared with the more commonly used peripheral vasodilator, dihydrallazine (Nepresol; Ciba), each administered as an infusion, in the treatment of severe hypertension in 20 primigravidas at greater than or equal to 32 weeks' gestation. With the dosage regimen used in this study there was a tendency towards more effective blood pressure control with dihydrallazine. The pulse rate was unaffected by labetalol therapy and there were no harmful effects on the neonate or fetus directly attributable to either drug. To assess the efficacy and safety of nicardipine in comparison to labetalol in the initial management of severe hypertension in pregnancy. DESIGN. Randomized prospective study.
                The obstetric ward of the teaching hospital of Monastir Tunisia.
                Sixty consecutive pregnant women admitted beyond the 24th week of pregnancy with severe hypertension.
                Patients were randomly assigned to receive intravenously for 1 h either labetalol ( n=30) or nicardipine ( n=30). Treatment was titrated to achieve a 20% lowering of blood pressure (BP).
                Maternal BP and heart rate were measured at inclusion and repeatedly during the first hour following the drugs administration. Fetal heart rate was recorded throughout the study period. The main outcome endpoints were the success rate and the length of time needed to achieve the therapeutic goal. The rate of maternal and fetal adverse events and dose adjustments were also analyzed.
                Labetalol and nicardipine achieved the 20% lowering in BP in the same proportion (63% and 70% success rates, respectively). Overall nicardipine caused a significantly greater decrease in systolic and diastolic BP. No patient had any episode of hypotension. The length of time to achieve the BP goal was also similar (12 vs. 11 min, respectively). Both drugs were well tolerated except for a moderate tachycardia observed with the use of nicardipine.
                Nicardipine and labetalol are effective and safe in the initial treatment of severe hypertension of pregnancy. To compare the efficacy and safety of intravenous dihydralazine with ketanserin in the management of severe hypertension in the third trimester.
                A double blind randomised controlled trial, comparing 5 mg dihydralazine with 10 mg ketanserin after an intravenous infusion of 500 ml of a crystalloid solution. Medication was repeated every 20 min till the therapeutic goal of 90 mm Hg was reached, to a maximum of 4 dosages. Main outcome measures were treatment failures and emergency deliveries for fetal distress.
                The therapeutic goal was met more often in patients receiving dihydralazine (36/38 compared to 27/42; P < 0.01). The need for delivery for fetal distress did not differ (3 after dihydralazine, 1 after ketanserin, P = 0.29) No therapy related perinatal loss occurred, but one mother with an undiagnosed phaechromocytoma died 24 h after receiving dihydralazine.
                Ketanserin in this dosage is less effective to lower diastolic blood pressure. The place of a fluid load prior to dihydralazine needs to be further investigated, as fetal heart rate decelerations were less common than previously reported. The results of a prospective trial to evaluate the use of diazoxide and labetalol given intravenously in the management of severe hypertensive disease in pregnancy are presented. Both drugs had an efficient hypotensive action. The reduction in blood pressure in the labetalol group was better controlled and this may be a factor influencing perinatal outcome. Because of the freedom of maternal and fetal side-effects, labetalol given by intravenous infusion is a more appropriate drug for use in the management of hypertensive crises occurring in pregnancy and labour. The objective was to compare the fetal and maternal effects between parenteral hydralazine and sublingual nifedipine used like antihypertensive drugs in the management of severe preeclampsia. Study design was prospective, comparative, longitudinal, randomized clinical trial. It was carried out at Centro Medico Nacional IMSS Torreon, Coah. Gynecology and Obstetrics Department. The patients were women in the last trimester of pregnancy with severe preeclampsia were randomized to receive parenteral hydralazine or sublingual nifedipine as antihypertensive drugs. The only difference observed in this study was the Apgar of neonates whose mothers received hydralazine, that was significatively lesser than the Apgar of neonates whose mothers received nifedipine. Both medicaments are a good alternative as antihypertensive drugs in severe preeclampsia. Neonates whose mothers received Nifedipine had a higher Apgar. In this assay, we evaluated the utility of isosorbide given by a sprayer in the management of hypertensive crisis of severe preeclampsia. 36 pregnant women with severe preeclampsia received fluid therapy and were randomly dividend in two groups of 18 patients each. Group A, received isosorbide in spray 1.25 mg when admitted and a second dose 10 minutes after if mean arterial blood pressure decreased less than 15%. and group B, in whom 4 g of magnesium sulphate was infused in one hour and then 1 g each hour for a maximum of five hours. In all patients blood pressure, proteinuria, fetal and maternal heart rate and Apgar score at minute and five minutes were obtained. In Group A 13 patients had a significative blood pressure reduction with one application and 5 needed a second one (p < 0.002). fetal (p < 0.005), and maternal (p < 0.005) heart rate also had a significative reduction. Whereas three patients in Group B did not respond and the rest had a poor blood pressure control (p > 0.05) with no changes in fetal and maternal heart rate. No patient developed eclampsia. When compared both groups, there were a significative difference for blood pressure (p < 0.005), fetal heart rate (p < 0.002), maternal heart rate (p < 0.05) and Apgar at minute (p < 0.01) in isosorbide's group. Our data suggest that isosorbide given by a sprayer is effective and safer in the management of the hypertensive crisis of severe preeclampsia. Pre-eclampsia is one of the most serious and common complications of pregnancy. Nifedipine, a calcium channel blocker, and the vasodilator hydralazine have both been used as antihypertensive agents in this condition. The aim of this study was to determine which of these two agents is the most appropriate antihypertensive in the management of severe pre-eclampsia.
                One hundred and twenty-six pre-eclamptic patients with a gestational age of more than 20 weeks were randomized to receive either 8 mg nifedipine sublingually or 5-10 mg intravenous hydralazine. Women with a history of heart failure and women receiving antihypertensive treatment during the course of the current pregnancy were excluded. For each patient the following data were recorded; the number of drug administrations, the time needed to control blood pressure, mean urinary output, the time interval between effective control and a new hypertensive crisis after each drug administration and relevant adverse effects in mother or fetus.
                Effective control of blood pressure was achieved in both treatment arms. Data analysis indicated significantly fewer drug administrations in the nifedipine arm of the study. The time interval before a new hypertensive crisis following initial effective control of blood pressure was significantly longer in the nifedipine group when compared with hydralazine. Effective control of blood pressure was achieved more rapidly in multiparous patients receiving nifedipine (p=0.026). Mean urinary output before and after delivery was greater in the nifedipine arm of the study. There were no significant differences between the two groups in other variables. In addition, in neither group were there any serious adverse effects in mother or fetus.
                Nifedipine is safe and more effective than hydralazine in controlling blood pressure in severe pre-eclampsia. It has the added advantage of being cheaper and more widely available than the latter and is easily administered. The primary objective of treatment in women with severe hypertension and pre-eclampsia is to prevent complications such as encephalopathy and haemorrhage. In many countries dihydralazine is considered the drug of choice for treating hypertension in pregnancy, because it now has been used safely for about 30 years, and the introduction of a new drug in pregnancy is a difficult task with partially unknown hazards. In some other countries combined alpha- and beta-blockers are also used. Taking into account that some patients with pre-eclampsia do not respond to dihydralazine and the drug has serious side-effects like headache and reflex tachycardia, there is some need for developing alternative treatment strategies using drugs that are more adequate for pregnancy than dihydralazine.
                Urapidil is a post-synaptic alpha 1 adrenoceptor antagonist, which is widely used to control hypertensive crises unrelated to pregnancy. Since it is known that pre-eclampsia is associated with increased sympathetic activity, administration of an alpha 1 adrenoceptor antagonist provides a reasonable therapeutic basis. So far there is only one report describing the i.v. use of urapidil in the treatment of hypertension in pregnancy unresponsive to dihydralazine and one report which describes the oral use of urapidil. In an earlier pilot study we examined the dose range for i.v. application of urapidil necessary for adequate blood pressure control in patients with pre-eclampsia. In the present randomized controlled study 26 white women with pre-eclampsia and hypertension in pregnancy were included. Treatment was not blinded. During the initial period of intensive intravenous treatment all subjects were under constant surveillance by a physician and a nurse.
                Effective prolonged control of blood pressure (values below 150/100 mmHg) was achieved in all patients of the two groups. In one patient of the dihydralazine group signs of lightheadedness and near syncope were noted. After this side-effect of dihydralazine the patient was treated with urapidil. At the end of the observation period the maternal heart rate in the dihydralazine group was higher than in the urapidil group.
                Since urapidil decreased the high blood pressure in patients with pre-eclampsia without serious side-effects urapidil appears preferable superior to dihydralazine. The haemodynamic effects of urapidil were more predictable than those of dihydralazine. The reduction of intracerebral pressure could be an additional advantage of urapidil in the treatment of patients with pre-eclampsia. The effect of nifedipine (Adalat; Bayer-Miles)--a calcium channel blocker, which has a well-established place in nonobstetric hypertension--was compared with dihydralazine in 33 primigravidas with severe hypertension of pregnancy. Patients with a diastolic blood pressure greater than 110 mmHg before drug administration were randomly assigned to treatment with either nifedipine or dihydralazine. Both drugs were found to be equally efficacious. Nifedipine, however, showed an earlier onset of action in lowering systolic blood pressure and had the advantage of oral administration. Intravenous treatment with 10 mg of hydralazine or 100 mg of labetalol was randomly allocated to 30 hypertensive pregnant women. Umbilical artery flow velocity waveforms were recorded using a pulsed Doppler duplex scanner (ATL Mk V) and umbilical artery pulsatility index (PI) and fetal heart rate (FHR) were derived from these recordings. Maternal blood pressure decreased significantly after both drugs. Maternal pulse rate increased after hydralazine but did not change significantly after labetalol. FHR did not change significantly after hydralazine but decreased after labetalol. PI decreased after hydralazine and increased after labetalol--most fetuses showed little change but a few in each group showed large changes in PI, as did two of five additional patients studied. We attributed the decrease in PI in some fetuses after hydralazine to vasodilation, and the increase in PI in some fetuses after labetalol to vasoconstriction in the fetoplacental circulation, suggesting that fetal beta-blockade may occur after maternal treatment with labetalol. Magnesium sulfate may prevent eclampsia by reducing cerebral vasoconstriction and ischemia. Nimodipine is a calcium-channel blocker with specific cerebral vasodilator activity. Our objective was to determine whether nimodipine is more effective than magnesium sulfate for seizure prophylaxis in women with severe preeclampsia.
                We conducted an unblinded, multicenter trial in which 1650 women with severe preeclampsia were randomly assigned to receive either nimodipine (60 mg orally every 4 hours) or intravenous magnesium sulfate (given according to the institutional protocol) from enrollment until 24 hours post partum. High blood pressure was controlled with intravenous hydralazine as needed. The primary outcome measure was the development of eclampsia, as defined by a witnessed tonic-clonic seizure.
                Demographic and clinical characteristics were similar in the two groups. The women who received nimodipine were more likely to have a seizure than those who received magnesium sulfate (21 of 819 [2.6 percent] vs. 7 of 831 [0.8 percent], P=0.01). The adjusted risk ratio for eclampsia associated with nimodipine, as compared with magnesium sulfate, was 3.2 (95 percent confidence interval, 1.1 to 9.1). The antepartum seizure rates did not differ significantly between groups, but the nimodipine group had a higher rate of postpartum seizures (9 of 819 [1.1 percent] vs. 0 of 831, P=0.01). There were no significant differences in neonatal outcome between the two groups. More women in the magnesium sulfate group than in the nimodipine group needed hydralazine to control blood pressure (54.3 percent vs. 45.7 percent, P<0.001).
                Magnesium sulfate is more effective than nimodipine for prophylaxis against seizures in women with severe preeclampsia.
                Copyright 2003 Massachusetts Medical Society An open, randomized, prospective, multicenter trial was conducted to compare the efficacy and safety of intravenous ketanserin, a selective serotonin 2 receptor blocker, with that of intravenous dihydralazine in the management of severe early-onset (<32 weeks' gestation) preeclampsia. End points of this study were blood pressure control and maternal outcome.
                Patients with a diastolic blood pressure >110 mm Hg were randomly assigned to receive either ketanserin (n = 22) or dihydralazine (n = 22) as initial therapy. Plasma volume expansion preceded antihypertensive treatment, which was administered according to a fixed schedule.
                The reductions in blood pressure with the 2 drugs were similar; however, adequate blood pressure control was reached significantly earlier with ketanserin (84 +/_ 63 vs 171 +/- 142 minutes, P = .017). Occurrence of maternal complications was significantly lower among patients who received ketanserin than among patients who received dihydralazine (n = 6 vs n = 18, P =.0007). A significant difference in favor of ketanserin was noted in daily fluid balance.
                Antihypertensive efficacies of ketanserin and dihydralazine were comparable, but significantly fewer maternal complications were noted among the patients receiving ketanserin. Ketanserin is an attractive alternative in the management of severe early-onset preeclampsia. Sixty peripartum patients with diastolic blood pressures (BP) 110 mmHg or higher were randomized in a 2:1 ratio to receive repeated intravenous injections of either labetalol (20-80 mg) or hydralazine (5 mg) until the diastolic BP was below 100 mmHg. There were four treatment failures in the labetalol group (N = 40) and none in the hydralazine group (N = 20). Hydralazine lowered mean arterial pressure (MAP) more than did labetalol (33.3 +/- 13.2 versus 25.5 +/- 11.2 mmHg; mean +/- SD), but labetalol had a more rapid effect. There was considerable interpatient variability in the dose of labetalol required to control BP, which could not be predicted by any clinical characteristic before therapy. The duration of action also varied in the labetalol group, with the shortest duration occurring in those patients who required the highest dosage for BP control. No significant fetal or neonatal problems ascribable to drug treatment were noted in the 13 instances in which labetalol was given before delivery. However, fetal distress occurred in two of the six cases involving antenatal hydralazine. We conclude that labetalol appears to be a safe and effective alternative to hydralazine for treating hypertension in the peripartum period, but serious rare side effects have not yet been quantified. To compare the antihypertensive effects of epoprostenol sodium (prostacyclin) with that of dihydralazine in acute hypertensive crises of pregnancy.
                A prospective randomized study. A minimum of 20 patients per group was considered statistically acceptable (alpha = 0.05, power = 0.9).
                A large urban tertiary hospital.
                Forty-seven pregnant patients with diastolic blood pressures of > 100 mmHg were studied.
                Lowering of high blood pressure with either dihydralazine (n = 25), the standard drug for this purpose, or epoprostenol (n = 22).
                A significant drop in high blood pressure was regarded as a fall of 15 mmHg diastolic and 30 mmHg systolic blood pressure.
                There were no statistically significant differences in the antihypertensive effects between the two treatment groups. Epoprostenol infusion caused less tachycardia; the mean pulse rate changed from 81.77 beats/min, before treatment to 88.36 at stabilization, compared with a change from 80.96 beats/min to 102.68 in the group treated with dihydralazine (P = 0.0024).
                The place of epoprostenol in pregnancy might be in patients with severe hypertension and tachycardia and in those requiring acute control of severe hypertension on the operating table before general anaesthesia. To compare ketanserin with hydralazine in the treatment of hypertension in late pregnancy.
                Randomised control trial. Ten milligrams ketanserin were compared with 5 mg hydralazine, both given intravenously to 10 patients in each group. Blood pressure, maternal and fetal heart rate and umbilical and arcuate artery Doppler flow velocimetry waveforms were recorded before and every 10 minutes after administration of the drug.
                No significant differences were found between the two drugs in respect of initial blood pressures and readings taken 10 minutes after each 30-minute administration. One patient in the hydralazine group developed severe hypotension and fetal distress for which a caesarean section was performed. No change in the flow velocity waveforms of umbilical and arcuate arteries was noticed.
                No unforeseen complications followed the administration of ketanserin. No major differences in the effects of the two drugs could be detected. Ketanserin appears to be safer as no hypotension occurred, and it reduced blood pressure more gradually. As ketanserin could become an alternative to hydralazine, more studies with larger numbers of patients are needed to compare it with hydralazine.
Until better evidence is available, the choice of antihypertensive should depend on the clinician's experience and familiarity with a particular drug, and on what is known about adverse effects. Exceptions are diazoxide, ketanserin, nimodipine and magnesium sulphate, which are probably best avoided.
[Note: The 37 citations in the awaiting classification section of the review may alter the conclusions of the review once assessed.]