Oral antihypertensive regimens (nifedipine retard, labetalol, and methyldopa) for management of severe hypertension in pregnancy: an open-label, randomised controlled trial.

BACKGROUND: Hypertension is the most common medical disorder in pregnancy, complicating one in ten pregnancies. Treatment of severely increased blood pressure is widely recommended to reduce the risk for maternal complications. Regimens for the acute treatment of severe hypertension typically include intravenous medications. Although effective, these drugs require venous access and careful fetal monitoring and might not be feasible in busy or low-resource environments. We therefore aimed to compare the efficacy and safety of three oral drugs, labetalol, nifedipine retard, and methyldopa for the management of severe hypertension in pregnancy. METHODS: In this multicentre, parallel-group, open-label, randomised controlled trial, we compared these oral antihypertensives in two public hospitals in Nagpur, India. Pregnant women were eligible for the trial if they were aged at least 18 years; they were pregnant with fetuses that had reached a gestational age of at least 28 weeks; they required pharmacological blood pressure control for severe hypertension (systolic blood pressure ≥160 mm Hg or diastolic blood pressure ≥110 mm Hg); and were able to swallow oral medications. Women were randomly assigned to receive 10 mg oral nifedipine, 200 mg oral labetalol (hourly, in both of which the dose could be escalated if hypertension was maintained), or 1000 mg methyldopa (a single dose, without dose escalation). Masking of participants, study investigators, and care providers to group allocation was not possible because of different escalation protocols in the study groups. The primary outcome was blood pressure control (defined as 120-150 mm Hg systolic blood pressure and 70-100 mm Hg diastolic blood pressure) within 6 h with no adverse outcomes. This study is registered with ClinicalTrials.gov, number NCT01912677, and the Clinical Trial Registry, India, number ctri/2013/08/003866. FINDINGS: Between April 1, 2015, and Aug 21, 2017, we screened 2307 women for their inclusion in the study. We excluded 1413 (61%) women who were ineligible, declined to participate, had impending eclampsia, were in active labour, or had a combination of these factors. 11 (4%) women in the nifedipine group, ten (3%) women in the labetalol group, and 11 (4%) women in the methyldopa group were ineligible for treatment (because they had only one qualifying blood pressure measurement) or had treatment stopped (because of delivery or transfer elsewhere). 894 (39%) women were randomly assigned to a treatment group and were included in the intention-to-treat analysis: 298 (33%) women were assigned to receive nifedipine, 295 (33%) women were assigned to receive labetalol, and 301 (33%) women were assigned to receive methyldopa. The primary outcome was significantly more common in women in the nifedipine group than in those in the methyldopa group (249 [84%] women vs 230 [76%] women; p=0·03). However, the primary outcome did not differ between the nifedipine and labetalol groups (249 [84%] women vs 228 [77%] women; p=0·05) or the labetalol and methyldopa groups (p=0·80). Seven serious adverse events (1% of births) were reported during the study: one (<1%) woman in the labetalol group had an intrapartum seizure and six (1%) neonates (one [<1%] neonate in the nifedipine group, two [1%] neonates in the labetalol group, and three [1%] neonates in the methyldopa group) were stillborn. No birth had more than one adverse event. INTERPRETATION: All oral antihypertensives reduced blood pressure to the reference range in most women. As single drugs, nifedipine retard use resulted in a greater frequency of primary outcome attainment than labetalol or methyldopa use. All three oral drugs-methyldopa, nifedipine, and labetalol-are viable initial options for treating severe hypertension in low-resource settings. FUNDING: PREEMPT (University of British Columbia, Vancouver, BC, Canada; grantee of Bill & Melinda Gates Foundation).

Oral nifedipine versus intravenous labetalol for severe hypertension during pregnancy: a systematic review and meta-analysis.

BACKGROUND: Oral nifedipine is recommended along with labetalol and hydralazine for treatment of severe hypertension during pregnancy by most authorities. Although nifedipine is cheap and easily administered, the usage pattern among health care providers suggests a strong preference for labetalol despite lack of evidence for the same. OBJECTIVES: To determine the efficacy and safety of oral nifedipine for treatment of severe hypertension of pregnancy compared with intravenous labetalol. SEARCH STRATEGY: We systematically searched for articles comparing oral nifedipine with intravenous labetalol for the treatment of severe hypertension during pregnancy in any language, over Medline, Cochrane Central Register of Clinical Trials and Google Scholar from inception till February 2014. SELECTION CRITERIA: We included all RCTs that compared intravenous labetalol with oral nifedipine for treatment of severe hypertension during pregnancy, addressing relevant efficacy and safety outcomes. DATA COLLECTION AND ANALYSIS: Eligible studies were reviewed, and data were extracted onto a standard form. We used Cochrane review manager software for quantitative analysis. Data were analysed using a fixed effect model. MAIN RESULTS: The pooled analysis of seven trials (four from developing countries) consisting of 363 woman-infant pairs showed that oral nifedipine was associated with less risk of persistent hypertension (RR 0.42, 95% CI 0.18-0.96) and reported maternal side effects (RR 0.57, 95% CI 0.35-0.94). However, on sensitivity analysis the outcome 'persistent hypertension' was no longer significant. Other outcomes did not reach statistical significance. CONCLUSION: Oral nifedipine is as efficacious and safe as intravenous labetalol and may have an edge in low resource settings. TWEETABLE ABSTRACT: Although studies to date are few in number and small, nifedipine shows promise for severe hypertension in pregnancy.

Comparison of labetalol and lidocaine in induction of controlled hypotension in tympanoplasty: a randomized clinical trial.

OBJECTIVES: This study aimed to compare the efficacy of labetalol and lidocaine in tympanoplasty surgery, specifically evaluating their impact on hemodynamic changes and perioperative outcomes. METHODS: A randomized controlled trial was conducted with 64 patients scheduled for tympanoplasty. Patients were randomly assigned to receive either 0.5-2 mg/min labetalol or 1.5 mg/kg/h lidocaine 1% to achieve controlled hypotension during surgery. The efficacy of the drugs was assessed by comparing the Mean Arterial Pressure (MAP), surgeon's satisfaction, time to target MAP, bleeding volume, postoperative pain scores, the need for analgesic medication in recovery, sedation, and other additional parameters. RESULTS: The hemodynamic parameters showed a similar trend over time in both the labetalol and lidocaine groups. The median bleeding volume in the labetalol group (10 cc) was lower than that in the lidocaine group (30 cc), although this difference was not statistically significant (p = 0.11). Similarly, surgeon's satisfaction level, pain intensity, and sedation level in the recovery room did not show statistically significant differences between the two groups (p > 0.05). The duration of surgery, recovery stay, and extubation time also did not significantly differ between the groups. Both medications took approximately the same time (20 min) to reach the target MAP and exhibited comparable hemodynamic responses (p > 0.05). CONCLUSION: Both labetalol and lidocaine effectively achieved controlled hypotension during tympanoplasty surgery, thereby improving surgical conditions. The choice of medication should be based on individual patient characteristics and the anesthesiologist's judgment. LEVEL OF EVIDENCE: II.

Acute intramural hematoma of the aorta complicated by spinal cord ischemia.

We present an unusual case of spinal cord ischemia from an acute type B intramural hematoma that was successfully treated with blood pressure elevation and drainage of cerebral spinal fluid.

Labetalol Versus Nifedipine as Antihypertensive Treatment for Chronic Hypertension in Pregnancy: A Randomized Controlled Trial.

Data from randomized controlled trials to guide antihypertensive agent choice for chronic hypertension in pregnancy are limited; this study aimed to compare labetalol and nifedipine, additionally assessing the impact of ethnicity on treatment efficacy. Pregnant women with chronic hypertension (12+0-27+6 weeks' gestation) were enrolled at 4 UK centers (August 2014 to October 2015). Open-label first-line antihypertensive treatment was randomly assigned: labetalol- (200-1800 mg/d) or nifedipine-modified release (20-80 mg/d). Analysis included 112 women (98%) who completed the study (labetalol n=55, nifedipine n=57). Maximum blood pressure after randomization was 161/101 mm Hg with labetalol versus 163/105 mm Hg with nifedipine (mean difference systolic: 1.2 mm Hg [-4.9 to 7.2 mm Hg], diastolic: 3.3 mm Hg [-0.6 to 7.3 mm Hg]). Mean blood pressure was 134/84 mm Hg with labetalol and 134/85 mm Hg with nifedipine (mean difference systolic: 0.3 mm Hg [-2.8 to 3.4 mm Hg], and diastolic: -1.9 mm Hg [-4.1 to 0.3 mm Hg]). Nifedipine use was associated with a 7.4-mm Hg reduction (-14.4 to -0.4 mm Hg) in central aortic pressure, measured by pulse wave analysis. No difference in treatment effect was observed in black women (n=63), but a mean 4 mm Hg reduction (-6.6 to -0.8 mm Hg; P=0.015) in brachial diastolic blood pressure was observed with labetalol compared with nifedipine in non-black women (n=49). Labetalol and nifedipine control mean blood pressure to target in pregnant women with chronic hypertension. This study provides support for a larger definitive trial scrutinizing the benefits and side effects of first-line antihypertensive treatment. CLINICAL TRIAL REGISTRATION: URL: https://www.isrctn.com. Unique identifier: ISRCTN40973936.

Severe hypertension in pregnancy: hydralazine or labetalol. A randomized clinical trial.

OBJECTIVE: The objective was to compare the safety and efficacy of intravenous labetalol and intravenous hydralazine for acutely lowering blood pressure in pregnancy. STUDY DESIGN: Two hundred women with severe hypertension in pregnancy were randomized to receive hydralazine (5 mg as a slow bolus dose given intravenously, and repeated every 20 min up to a maximum of five doses) or labetalol (20-mg intravenous bolus dose followed by 40 mg if not effective within 20 min, followed by 80 mg every 20 min up to a maximum dose of 300 mg). The primary end point was successful lowering of blood pressure and maternal hypotension. RESULTS: Women were similar with respect to characteristics at randomization. No significant differences were observed for maternal hypotension or persistent severe hypertension; only two patients in the hydralazine group presented with hypotension. Palpitations (p=0.01) and maternal tachycardia (p=0.05) occurred significantly more often in patients treated with hydralazine. The main neonatal outcomes were very similar per group; however, hypotension and bradycardia were significantly more frequent in the labetalol group. There were two neonatal deaths per antihypertensive drug group. CONCLUSIONS: This randomized clinical trial shows that labetalol and hydralazine fulfill the criteria required for an antihypertensive drug to treat severe hypertension in pregnancy.

A review of oral labetalol and nifedipine in mild to moderate hypertension in pregnancy.

Hypertension is the most commonly encountered medical condition in pregnancy, contributing significantly to maternal and perinatal morbidity and mortality. Mild to moderate hypertension in pregnancy is defined as systolic blood pressure of 140-159 mmHg or diastolic blood pressure of 90-109 mmHg (7-9% of pregnancies). When treating hypertension in pregnancy, not only do physiologic changes of pregnancy have an effect on the pharmacokinetics and pharmacodynamics of the drugs used, but the pathophysiology of hypertensive disorders of pregnancy also have an effect. To date, evidence is lacking on the pharmacokinetics and pharmacodynamics of commonly used antihypertensive drugs, which often times leads to suboptimal treatment of hypertensive pregnant women. When considering which agents to use for treatment of mild to moderate hypertension, specifically in gestational and chronic hypertension, oral labetalol and nifedipine are valid options. An overview of the profile for use, safety, and current pharmacokinetic data for each agent is presented here.

Analgesic effect of peridural labetalol in the treatment of cancer pain.

Labetalol is an alpha- and beta-blocking agent commonly used in anti-hypertensive therapy. Because of its beta-blocking and local anesthetic effect, labetalol via peridural catheter was supposed to reduce pain in patients suffering from gynecologic cancers. Thirty patients with terminal carcinomas (breast, uterus, ovary), whose pain was caused either by bone metastases or by primary invasion cancer, were treated. Peridural catheters were inserted and fixed at various levels, thoracic or lumbar, and 50 mg labetalol was injected every 4 h at the beginning and every 12-24 h on the following 2-3 days. The analgesia started immediately during the injection. No sensitive damage or neurovegetative block appeared. In 40% of the patients the catheter was removed after a 3-day treatment because of the definitive suppression of pain. Other analgesics were not required during the treatment; no tolerance to the drug was developed. The peridural catheter remained in situ for an average period of 4-30 days. Afterward it was possible to treat more cases as outpatients depending on their general conditions and with the help of their family doctors. After a few days of therapy, almost all the patients reported a burning pain at the site of the injection; this problem was easily resolved by prior injection of a 4-mg dose of betamethasone.

Induced hypotension with labetalol for orthognathic surgery.

Induced hypotension is an accepted technique for reducing blood loss in various surgical procedures. This study evaluates the effectiveness of labetalol in producing controlled reduction in mean arterial pressure during orthognathic surgery. The potential advantages of this technique are ease of administration, decreased pulmonary shunting, and absence of tachycardia or rebound hypertension compared to other commonly used agents.

Labetalol in general practice: a review.

1 The results of the treatment of 8573 hypertensive patients with labetalol in general practice, for periods between 1 month and 5 yr, are reviewed. 2 The data reviewed were obtained from the published literature together with our own published (Kane et al., 1976; Kane et al., 1979) and more recent (unpublished) work. 3 Between 60% and 80% of severe (diastolic blood pressure greater than 120 mmHg) and previously uncontrolled hypertensives responded satisfactorily to the drug, as did up to 88% of mild to moderate hypertensives. 4 The anti-hypertensive effect of labetalol was not dependent on the frequency of administration, twice and three times daily treatment regimes being equally effective. 5 The withdrawal rate attributable to side-effects was between 6% and 13%. Tiredness, dizziness, headache and upper gastro-intestinal symptoms were the four principal side-effects, but they were usually transient when labetalol treatment was continued. 6 No drug interactions or adverse haematological or biochemical changes were seen.

Transesophageal echocardiographic assessment of left ventricular function in response to labetalol for control of postoperative hypertension.

Although labetalol (LAB), the combination of an alpha- and beta-adrenergic blocking agent, is thought to be effective and safe for the control of postoperative hypertension, no study has focused on changes in left ventricular (LV) function when this drug was used to control postoperative hypertension. Therefore, this study determined the effects of LAB on hemodynamics and LV function assessed by 2D transesophageal echocardiography (TEE) in 17 patients undergoing abdominal aortic surgery who experienced a postoperative hypertensive episode. Postoperatively, patients were transferred while still intubated and under fentanyl sedation to the postanesthesia care unit where a TEE probe was inserted to provide a short-axis view of the LV. When their systolic blood pressure increased above 165 mmHg for more than 4 minutes, LAB was given in a dose of 0.75 mg/kg IV, over 2 minutes. If the blood pressure was not lowered to within 10% of the preoperative values, additional doses of LAB were given. Control of hypertension was obtained in all patients and was associated with a significant decrease in heart rate (90 +/- 19 to 70 + 13 bpm), cardiac index (4.52 +/- 1.65 to 3.36 +/- 1.55 L/min/m2), and mixed venous oxygen saturation (73 +/- 10 to 63 +/- 10%). With the lower blood pressure, end-diastolic area increased, indicating myocardial depression. In conclusion, LAB can be used to effectively control hypertension during the early postoperative period after abdominal aortic surgery. However, the reduction of blood pressure is achieved principally by the negative inotropic effect of LAB, which predominates over its vasodilator action.