Search

Objective: To evaluate maternal and neonatal outcomes by type of antihypertensive used in participants of the CHAP (Chronic Hypertension in Pregnancy) trial., Methods: We conducted a planned secondary analysis of CHAP, an open-label, multicenter, randomized trial of antihypertensive treatment compared with standard care (no treatment unless severe hypertension developed) in pregnant patients with mild chronic hypertension (blood pressure 140-159/90-104 mm Hg before 20 weeks of gestation) and singleton pregnancies. We performed three comparisons based on medications prescribed at enrollment: labetalol compared with standard care, nifedipine compared with standard care, and labetalol compared with nifedipine. Although active compared with standard care groups were randomized, medication assignment within the active treatment group was not random but based on clinician or patient preference. The primary outcome was the occurrence of superimposed preeclampsia with severe features, preterm birth before 35 weeks of gestation, placental abruption, or fetal or neonatal death. The key secondary outcome was small for gestational age (SGA) neonates. We also compared medication adverse effects between groups. Relative risks (RRs) and 95% CIs were estimated with log binomial regression to adjust for confounding., Results: Of 2,292 participants analyzed, 720 (31.4%) received labetalol, 417 (18.2%) received nifedipine, and 1,155 (50.4%) received no treatment. The mean gestational age at enrollment was 10.5±3.7 weeks; nearly half of participants (47.5%) identified as non-Hispanic Black; and 44.5% used aspirin. The primary outcome occurred in 217 (30.1%), 130 (31.2%), and 427 (37.0%) in the labetalol, nifedipine, and standard care groups, respectively. Risk of the primary outcome was lower among those receiving treatment (labetalol use vs standard adjusted RR 0.82, 95% CI, 0.72-0.94; nifedipine use vs standard adjusted RR 0.84, 95% CI, 0.71-0.99), but there was no significant difference in risk when labetalol was compared with nifedipine (adjusted RR 0.98, 95% CI, 0.82-1.18). There were no significant differences in SGA or serious adverse events between participants receiving labetalol and those receiving nifedipine., Conclusion: No significant differences in predetermined maternal or neonatal outcomes were detected on the basis of the use of labetalol or nifedipine for treatment of chronic hypertension in pregnancy., Clinical Trial Registration: ClinicalTrials.gov, NCT02299414., Competing Interests: Financial Disclosure Brenna L. Hughes reports receiving payment from UpToDate. Rodney K. Edwards' institution received payment from the Oklahoma Center for Advancement of Science and Technology and the Presbyterian Health Foundation. He received payment from the NIH through Oklahoma CTR grant for a pilot trial on warming preterm infants during delayed cord clamping. He received a Presbyterian Health Foundation grant for a pilot trial on omega-3 fatty acid supplementation effects on maternal triglycerides and fetal growth. He received an NIH grant for evaluation of atherogenic lipoproteins changes with immediate prepregnancy intervention and whether they were maintained during pregnancy. He received a grant from Cepheid for the clinical evaluation of the Xpert Xpress GBS test using vaginal/rectal swabs collected intrapartum. He was awarded an Oklahoma State DOH contract for support for patient-centered, comprehensive pregnancy care for women with substance use disorders. He received an NIH grant for a multicenter RCT of intensive glycemic targets in women with overweight and obesity with GDM. Lastly, he has a pending NIH grant for a multicenter RCT of prophylactic antibiotics for induction of labor in women with obesity. He has served on an expert witness case regarding a medical malpractice claim. Kelly S. Gibson's institution received an NHCID-MFMU network grant and Materna Medical research support (EASE). She received payment from NIH as a RADx grant reviewer and was an Ohio AIM grant recipient as an AIM webinar speaker. Rachel Sinkey received funding paid to her institution from the NIH and the American Heart Association. Kelly S. Gibson reports her institution received an NHCID-MFMU network grant and Materna Medical research support (EASE). She received payment as a NIH-RADx grant reviewer. Torri D. Metz received UpToDate royalties for two topics on trial of labor after cesarean. Her institution received payment from Pfizer, as she has been a site PI for a phase III respiratory syncytial virus (RSV) vaccine trial (institution received money to conduct study). Her institution also received payment for her to serve as a site PI for a COVID-19 vaccination trial in pregnancy. She has received payment from Pfizer as a site PI for a pharmacokinetic study of Paxlovid in pregnancy for mild-to-moderate COVID-19. Sean Esplin received payment from Laborie. Mary E. Norton received payment from Luna Genetics. Daniel Skupski received payment from Organon and Cooper Surgical. Leonardo Pereira's institution received payment from Johnson & Johnson/Janssen Pharmaceuticals for an FDA trial on alloimmunization management. Everett F. Magann is a co-author on and UpToDate chapter on amniotic fluid volume assessment. Heather Frey also received royalties for contributions to UpToDate on the topic of uterine rupture. Alan T.N. Tita's institution received funding from Pfizer. Torri D. Metz received UpToDate royalties for two topics on trial of labor after cesarean. Her institution received payment from Pfizer, as she has been a site PI for a phase III respiratory syncytial virus (RSV) vaccine trial, a COVID-19 vaccine trial in pregnancy, and pharmacokinetic study of Paxlovid in pregnancy for mild-to-moderate COVID-19 (institution received money to conduct studies). Kara K. Hoppe's institution received an NIH grant for a multicenter RCT of remote blood pressure monitoring with health coaching versus standard of care, HHS funding for a hypertension challenge initiative, Marani to study implementation of their remote patient monitoring platform for hypertensive patients in pregnancy and postpartum. Additionally, she received payment for the NIH as a grant reviewer and WisPQC for providing physician leadership for the state quality initiative on hypertension in pregnancy. Eugene Chang received payment from Roche diagnostics for research on sflt-1/plgf. Sherri Longo acknowledges the financial support received for the Prospect study and other NIH-funded studies including CHAP maternal follow-up and CSOAP follow-up. She is also an investigator for the Moms on the Bayou research project with Tulane University and is receiving funding from the NIH Maternal Health Research Center of Excellence awarded to a collaborative effort between Tulane University, Ochsner Health, and RHI. Alan T.N. Tita's institution received funding from Pfizer. The other authors did not report any potential conflicts of interest., (Copyright © 2024 by the American College of Obstetricians and Gynecologists. Published by Wolters Kluwer Health, Inc. All rights reserved.)

Purpose: To assess the safety and efficacy of continuous infusion (CIV)-labetalol compared to -nicardipine in controlling blood pressure (BP) in the acute stroke setting., Materials: Patients were eligible if they had a diagnosis of an acute stroke and were administered either CIV-labetalol or CIV-nicardipine. Study outcomes were assessed within the first 24 h of the antihypertensive infusion., Results: A total of 3,093 patients were included with 3,008 patients in the CIV-nicardipine group and 85 in the CIV-labetalol group. No significant difference was observed in percent time at goal BP between the nicardipine (82%) and labetalol (85%) groups (p = 0.351). There was also no difference in BP variability between nicardipine (37%) and labetalol (39%) groups (p = 0.433). Labetalol was found to have a shorter time to goal BP as compared to nicardipine (24 min vs. 40 min; p = 0.021). While CIV-nicardipine did have a higher incidence of tachycardia compared to labetalol (17% vs. 4%; p <0.001), the incidence of hypotension (13% vs. 15%; p = 0.620) and bradycardia (24% vs. 22%; p = 0.797) were similar., Conclusions: These results indicate that CIV-labetalol and CIV-nicardipine are comparable in safety and efficacy in controlling BP for patients with acute stroke., Competing Interests: Declaration of Competing Interest The authors declare that they have no conflicts of interest., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Response to acute treatment of severe hypertension during pregnancy in Asian women was not known. Labor and delivery checklists of Thai women treated with intravenous hydralazine or labetalol for systolic blood pressure (SBP) ≥ 160 or diastolic blood pressure (DBP) ≥ 110 mm Hg from January 2011 to December 2013 were reviewed as parts of an audit. Primary outcome was prompt achievement of SBP 140-150 and DBP 90-100 mm Hg after the first bolus. Secondary outcomes were medication-related undesired effects. The mean ± standard deviation age and prevalence of chronic hypertension in hydralazine (n = 62) versus labetalol (n = 64) groups were 32.5 ± 6 versus 29.9 ± 6.8 years and 50% versus 21.9%, respectively (P < .05). Magnesium sulfate was promptly administered on admission to every woman to prevent seizure. Targeted blood pressure was timely achieved in 41.9% and 67.2% of the hydralazine and labetalol groups, respectively (P < .05). Nonreassuring fetal heart rate occurred in 51.6% and 32.8% of the hydralazine and labetalol groups, respectively (P = .05). The prevalence of cesarean section and Apgar score < 7 were not significantly different (P > .05). Real-life clinical experiences suggested significant advantages of intravenous labetalol over hydralazine in pregnant women with severe hypertension., (© 2020, The American College of Clinical Pharmacology.)

Intravenous (IV) hydralazine, enalapril and labetalol are oftentimes used without indication for the treatment of asymptomatic hypertension in the hospital setting and have been shown to have substantial adverse effects that are associated with increased morbidity and mortality, as well as longer length of stay. Their use is also associated with greater monetary costs. In this project, we studied the frequency of use and consequences of these medications before and after a series of education cycles which clarified when and when not to use intravenous antihypertensives (IVAHs). Our initial aim was to decrease the unindicated use of IVAH by at least 25% in the setting of asymptomatic hypertension in our community hospital within a 1-year period after introducing education on the topic. Multidisciplinary involvement throughout three Plan-Do-Study-Act (PDSA) cycles yielded favourable results. We focused on education towards a hospital-wide knowledge gap stemming from a lack of guidelines regarding the treatment of asymptomatic hypertension, as well as the guideline indications for IVAH. After three cycles of education targeting different groups, the unindicated use of IVAH fell by a total of 66%, decreasing patient exposure by approximately 248 cases over the total course of the study and ultimately, yielding a 52% increase in patient safety. Secondary outcome included a reduction in cost. It was noted that IV drugs cost more than their oral counterparts. The culture change in switching away from IVAH unless otherwise indicated was driven by repetitive education and group discussion to close the gap created by a lack of guidelines., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

The purpose of the study was to clarify whether short-acting antihypertensives are associated with the occurrence of ischemic stroke and intracerebral hemorrhage (ICH). This was a retrospective case-crossover study using the Taiwan National Health Insurance Research Database. We identified all adult patients hospitalized with a primary diagnosis of ischemic stroke or ICH between January 2005 and December 2013. For each case, short-term and long-term exposure to short-acting antihypertensives, including nifedipine, labetalol and captopril, during the case vs. control periods were compared, and odd ratios (ORs) and 95% confidence intervals (CIs) for ischemic stroke or ICH were calculated with adjustment for confounders. Among 272785 ischemic stroke and 77798 ICH patients, the mean age was 77.8 ± 14.3 years and 70.8 ± 16.6 years, respectively. The short-term use of the three short-acting antihypertensives were all associated with an increase in the incidence of ischemic stroke (nifedipine: OR 4.51, 95% CIs 3.99-5.11; labetalol: OR 2.07; 95% CIs 1.71-2.51; captopril: OR 1.98, 95% CIs 1.72-2.29) and ICH (nifedipine: OR 2.98, 95% CIs 2.30-3.84; labetalol: OR 2.37; 95% CIs 1.66-3.39; captopril: OR 2.48; 95% CIs 1.69-3.63). The long-term use of short-acting nifedipine for 30 days was associated with a modest increase in the risk for ischemic stroke (OR 1.86; 95% CIs 1.42-2.45). Overall, the short-term use of short-acting antihypertensives is associated with a modest increase in the incidence of stroke, and short-acting nifedipine is linked to a substantial rise in the incidence of ischemic stroke. The long-term use of short-acting nifedipine was also related to an increased incidence of ischemic stroke. Physicians should be cautious of prescribing these short-acting antihypertensives.

Background: Hypertensive emergency is commonly associated with acute ischemic stroke and can be a predictor of poor outcome in these patients. Nicardipine and labetalol are commonly administered for the treatment of acute hypertension following stroke. Yet, data are lacking on the safety of these agents in this setting., Objective: This study aimed to determine all-cause in-hospital mortality, medication-related hypotensive episodes, development of hospital acquired infections and hospital length of stay between nicardipine and labetalol use for the management of hypertension after acute ischemic stroke., Methods: This retrospective study used a prospective database of individuals admitted to the neurointensive care unit at a university-based hospital over 39 months. Patients with confirmed ischemic strokes were included in this analysis. Data were recorded for administration of nicardipine and labetalol following acute stroke., Results: A total of 244 patients with acute ischemic stroke were included in this analysis (mean age, 64.3 ± 15 years; 52.2% males). Nicardipine use after acute ischemic stroke was associated with an increased risk of 30-day mortality (odds ratio [OR]: 4.6, 95% confidence interval [CI] 1.3-15.7; P = .02). A single episode of hypotension in the first 72hours of admission was also significantly associated with mortality (OR 4.35 [95% CI 1.2-14.9]; P = .02)., Conclusions: Nicardipine was associated with an increased risk of short-term mortality after acute ischemic stroke. This may have been due to hypotension, tachycardia, or pulmonary edema which were not apparent in our study. Further studies are required to elucidate the cause of this association., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Neonatal hypertension is increasingly recognized as dramatic improvements in neonatal intensive care, advancements in our understanding of neonatal physiology, and implementation of new therapies have led to improved survival of premature infants. A variety of factors appear to be important in determining blood pressure in neonates, including gestational age, birth weight, and postmenstrual age. Normative data on neonatal blood pressure values remain limited. The cause of hypertension in an affected neonate is often identified with careful diagnostic evaluation, with the most common causes being umbilical catheter-associated thrombosis, renal parenchymal disease, and chronic lung disease. Clinical expertise may need to be relied upon to decide the best approach to treatment in such patients, as data on the use of antihypertensive medications in this age group are extremely limited. Available data suggest that long-term outcomes are usually good, with resolution of hypertension in most infants. In this review, we will take a case-based approach to illustrate these concepts and to point out important evidence gaps that need to be addressed so that management of neonatal hypertension may be improved.

Background: Asymptomatic blood pressure elevation is common in the inpatient setting. National guidelines recommend treating with oral agents to slowly decrease blood pressure; however, many clinicians use intravenous antihypertensive medications, which can lead to unpredictable changes in blood pressure., Objective: To decrease the number of inappropriate orders (without symptoms of hypertensive emergency or order for NPO) of intravenous antihypertensives and adverse events associated with intravenous orders., Design: Quasi-experimental study with multidisciplinary intervention., Participants: Inpatients with a one-time order for an intravenous antihypertensive agent from January 2016 to February 2018., Main Measures: The main outcomes were the total numbers of orders and inappropriate orders, adverse events, and alternate etiologies per 1,000 patient-days. As a balancing measure, patients were monitored for adverse events when blood pressure was elevated and not treated., Key Results: There were a total of 260 one-time orders of intravenous antihypertensives on two medical units. Inappropriate orders decreased from 8.3 to 3.3 per 1,000 patient days (P = .0099). Adverse events associated with intravenous antihypertensives decreased from 3.7 to 0.8 per 1,000 patient days (P = .0072)., Conclusion: This initiative demonstrated a significant reduction in inappropriate use of IV antihypertensives and an associated reduction in adverse events.

Purpose: The study assesses the safety of high-dose intravenous (i.v.) labetalol in adults., Methods: This is a retrospective administrative record review of 28 hospitals in one health care system, from October 2010 through October 2015. Patients were included if they received 300 mg of i.v. labetalol within a 24-hour period. Vital signs, adverse events and cumulative medication doses were obtained for up to 24 hours while on labetalol. Adverse events were defined as any systolic blood pressure measurement less than 90 mm Hg or heart rate less than 60 beats per minute., Results: We analyzed the records of 188 patients who received i.v. labetalol at higher than the maximum recommended dose of 300 mg. The mean dose of labetalol was 996 mg (range 300 to 4465 mg). The cumulative labetalol dose was not associated with adverse safety outcomes (p = 0.428), although eighty-one patients (44.3%) experienced adverse events. Sixty-six patients (36.5%) developed bradycardia and 34 patients (18.6%) developed hypotension. Only five patients (2.7%) required a rescue agent for refractory adverse events., Conclusion: A retrospective review of high-dose i.v. labetalol hydrochloride with doses greater than 300 mg in 24 hours observed a high rate of bradycardia and hypotension, but the study found that these events rarely caused clinically significant hemodynamic compromise and was not statistically associated with adverse events.

Beta-blockers are one of the most commonly prescribed classes of antihypertensive medications during pregnancy. Previous studies reported an association between beta-blocker exposure and intrauterine growth restriction. Whether some beta-blocker subtypes may be associated with higher risk is not known. This is a retrospective cohort study of pregnant women exposed to beta-blockers in the Kaiser Permanente Southern California Region between 2003 and 2014. Logistic regression models were used to evaluate association between exposure to different beta-blocker agents and risk of low fetal birth weights. In a cohort of 379 238 singleton pregnancies, 4847 (1.3%) were exposed to beta-blockers. The four most commonly prescribed beta-blockers were labetalol (n = 3357), atenolol (n = 638), propranolol (n = 489), and metoprolol (n = 324). Mean birth weight and % low birth weight (<2500 g) were 2926 ± 841 g and 24.4% for labetalol, 3058 ± 748 g and 18.0% for atenolol, 3163 ± 702 g and 13.3% for metoprolol, 3286 ± 651 g and 7.6% for propranolol, and 3353 ± 554 g and 5.2% for non-exposed controls. Exposure to atenolol and labetalol were associated with increased risks of infant born small for gestational age (SGA) (atenolol: adjusted OR 2.4, 95% CI: 1.7-3.3; labetalol: adjusted OR 2.9, 95% CI: 2.6-3.2). Risk of SGA associated with metoprolol or propranolol exposure was not significantly different from the non-exposed group (metoprolol: adjusted OR 1.5, 95% CI: 0.9-2.3; propranolol: adjusted OR 1.3, 95% CI: 0.9-1.9). Association between beta-blocker exposure and SGA does not appear to be a class effect. Variations in pharmacodynamics and confounding by indication may explain these findings., (©2018 Wiley Periodicals, Inc.)

Aims: Several antihypertensive drugs are used in the treatment of severe hypertension in pregnancy. The present study is a network meta-analysis comparing the efficacy and safety of these drugs., Methods: Electronic databases were searched for randomized clinical trials comparing drugs used in the treatment of severe hypertension in pregnancy. The number of women achieving the target blood pressure (BP) was the primary outcome. Doses required and time taken for achieving the target BP, failure rate, and incidences of maternal tachycardia, palpitation, hypotension, headache, and neonatal death and stillbirth were the secondary outcomes. Mixed treatment comparison pooled estimates were generated using a random-effects model. Odds ratios for the categorical and mean difference for the numerical outcomes were the effect estimates., Results: Fifty-one studies were included in the systematic review and 46 in the meta-analysis. No significant differences in the number of patients achieving target BP was observed between any of the drugs. Diazoxide [-15 (-20.6, -9.4)], nicardipine [-11.8 (-22.3, -1.2)], nifedipine/celastrol [-19.3 (-27.4, -11.1)], nifedipine/vitamin D [-17.1 (-25.7, -9.7)], nifedipine/resveratrol [-13.9 (-22.6, -5.2)] and glyceryl trinitrate [-33.8 (-36.7, -31)] were observed to achieve the target BP (in minutes) more rapidly than hydralazine. Nifedipine required fewer doses than hydralazine for achieving the target BP. Glyceryl trinitrate and labetalol were associated with fewer incidences of tachycardia and palpitation respectively than hydralazine. Trial sequential analysis concluded adequate evidence for hydralazine and nifedipine compared with labetalol. Moderate quality of evidence was observed for direct comparison estimate between labetalol and hydralazine but was either low or very low for other comparisons., Conclusion: The present evidence suggests similar efficacy between nifedipine, hydralazine and labetalol in the treatment of severe hypertension in pregnancy. Subtle differences may exist in their safety profile. The evidence is inadequate for other drugs., (© 2018 The British Pharmacological Society.)

Objective: To estimate whether the diagnosis of asthma is associated with the use of specific uterotonic and antihypertensive medications during delivery hospitalizations., Methods: We used Perspective, an administrative database, to determine whether women hospitalized for delivery complicated by postpartum hemorrhage or preeclampsia received uterotonics and antihypertensive medications differentially based on the absence or presence of asthma from 2006 to 2015. Given that carboprost and intravenous (IV) labetalol may be associated with asthma exacerbation, adjusted models for receipt of these medications were created with adjusted risk ratios with 95% CIs as measures of effect. Risk for status asthmaticus based on receipt of carboprost and IV labetalol was analyzed., Results: Over the study period, a total of 5,691,178 women were analyzed, of whom 239,915 (4.2%) had preeclampsia and 139,841 postpartum hemorrhage (2.5%). Carboprost was used less frequently in patients with asthma compared with patients with no asthma (11.4% vs 18.0%) in comparison with IV labetalol, which was used more commonly when a diagnosis of asthma was present (18.5% vs 16.7%). In unadjusted analysis, the presence of asthma was associated with a 37% decrease in likelihood of carboprost use and an 11% increase in likelihood of labetalol use. In adjusted analysis, the presence of asthma was associated with a 32% decrease in likelihood of carboprost use (adjusted risk ratio 0.68, 95% CI 0.62-0.74) compared with a 7% decrease in labetalol use (adjusted risk ratio 0.93, 95% CI 0.90-0.97). Risk for status asthmaticus was significantly increased with use of IV labetalol compared with other antihypertensive medications (6.5 vs 1.7/1,000 delivery hospitalizations, P<.01)., Conclusion: There may be an opportunity to reduce use of β-blockers and carboprost among patients with asthma. Given their association with status asthmaticus, these drugs should be used cautiously in women with asthma.

Background: Labetalol and nicardipine are antihypertensives commonly used in the management of elevated blood pressure (BP) following an acute stroke, but there is limited evidence to suggest which agent as a continuous infusion should be used preferentially in this setting., Objective: This study aimed to compare the safety, efficacy, and ease of administration of continuous-infusion labetalol with continuous-infusion nicardipine following an acute stroke., Methods: This retrospective cohort study of patients with acute ischemic stroke or intracerebral hemorrhage included patients if they received either study agent within 24 hours of admission. The primary outcome was percent time spent at goal BP. Secondary outcomes included time to goal BP, the number of dose adjustments, and use of rescue antihypertensives., Results: The analysis included 99 patients who received labetalol- (n = 34) or nicardipine- (n = 65) continuous infusions. Intracerebral hemorrhage was the most common stroke subset (n = 81) followed by acute ischemic stroke (n = 18). There was no statistical difference in time at goal BP (labetalol 68.0%, nicardipine 67.0%; P = .885), rescue antihypertensive use (labetalol 14.7%, nicardipine 24.6%; P = .2570), time spent 10% above or below mean systolic BP (labetalol 35.5%, nicardipine 33.5%; P = .885), time to goal BP (labetalol 81.4 minutes, nicardipine 56.3 minutes; P = .162), and mean number of dose adjustments (labetalol 5.9, nicardipine 6.9; P = .262)., Conclusions: Labetalol- and nicardipine-continuous infusions were comparable in the studied safety and efficacy outcomes including time at goal and BP variability. Further prospective studies are needed to validate these safety and efficacy findings and to assess clinical outcomes., (Copyright © 2018 National Stroke Association. Published by Elsevier Inc. All rights reserved.)

Aim: To compare the blood pressure (BP) lowering effects of labetalol and nifedipine modified release (MR) in hypertensive pregnant women. We also investigated the effect on the heart rate (HR) and determined the proportion of time spent in target., Methods: This was an exploratory study. Women with chronic hypertension taking either labetalol or nifedipine were offered 24-h ambulatory blood pressure monitoring (ABPM). Sleep, wake and drug ingestion times were self-reported. An indirect response model was used to analyse the systolic BP (SBP), diastolic BP (DBP) and HR time-series; the effect of gestation and type of drug was evaluated., Results: Forty-eight women were recruited: 24 in each group. There was no difference in clinical characteristics. In women taking nifedipine there was a positive association between the dose of nifedipine and pre-dose BP p = .002, this was not present in the labetalol group. There was a difference between the drug effects on both the SBP and DBP time-series (p = .014). In comparison to labetalol, there was less variation in day time BP in those women prescribed nifedipine. Women on labetalol spent a larger proportion of time with their DBP below target (<80 mmHg). The HR dynamics were qualitatively different, a stimulatory effect was found with nifedipine compared to an inhibitory effect with labetalol., Conclusion: There are significant and important differences between the BP lowering effects of nifedipine and labetalol. A large randomised control trial is required to investigate the relationship between BP variability and time in target on pregnancy outcomes., (Copyright © 2018 International Society for the Study of Hypertension in Pregnancy. Published by Elsevier B.V. All rights reserved.)

Background: The aim of this study was to evaluate the use of as-needed (PRN) labetalol and hydralazine [intravenous (IV) or oral] in hospitalized medicine patients for the treatment of severe asymptomatic hypertension and to examine the potential negative outcomes associated with their use., Methods: The electronic health record of 250 medicine patients hospitalized at the University of Colorado Hospital between November 2014 and April 2016 who received at least one dose of PRN IV or oral hydralazine or labetalol were retrospectively reviewed. The primary outcome was to describe the use of PRN antihypertensive medications in this population., Results: A total of 573 PRN doses of antihypertensive medication were administered. Oral hydralazine was the most common (521 doses, 90.9%). A total of 36% of PRN administrations were given for a systolic blood pressure (SBP) <180 mmHg and diastolic blood pressure (DBP) <110 mmHg (cut-point for acute severe hypertension). No serious adverse events were related to PRN antihypertensive administration. Despite receiving at least one PRN antihypertensive medication during hospitalization, 40.8% of patients were not continued on their home antihypertensive medication(s) while hospitalized, and 62.4% of patients did not have their home regimens intensified at discharge., Conclusion: As-needed oral hydralazine is frequently prescribed for acute blood pressure lowering with administration thresholds often less than what are used to define acute severe hypertension. Many patients are prescribed PRN antihypertensive medication instead of being continued on their home regimens, and most patients do not have the intensity of their home regimens increased. Providers need to be educated about the use of PRN antihypertensive medication for the management of severe asymptomatic hypertension in the hospital setting.

Background: Although medication is generally avoided wherever possible during pregnancy, pharmacotherapy is required for the treatment of pregnancy associated hypertension, which remains a leading cause of maternal and fetal morbidity and mortality. The long-term effects to the child of in-utero exposure to antihypertensive agents remains largely unknown., Objective: The aim of this study was to systematically review published studies on adverse outcomes to the child associated with in-utero exposure to antihypertensive medications., Methods: OVID, Scopus, EBSCO Collections, the Cochrane Library, and Web of Science databases were searched for relevant publications published between January 1950 and October 2016 and a total of 688 potentially eligible studies were identified., Results: Following review, 47 primary studies were eligible for inclusion. The Critical Appraisal Skills Programme checklist was used to assess study quality. Five studies were of excellent quality; the remainder were either mediocre or poor. Increased risk of low birth weight, low size for gestational age, preterm birth, and congenital defects following in-utero exposure to all antihypertensive agents were identified. Two studies reported an increased risk of attention deficit hyperactivity disorder following exposure to labetalol, and an increased risk of sleep disorders following exposure to methyldopa and clonidine., Conclusion: The current systematic review demonstrates a paucity of relevant published high-quality studies. A small number of studies suggest possible increased risk of adverse child health outcomes; however, most published studies have methodological weaknesses and/or lacked statistical power thus preventing any firm conclusions being drawn.

Objective: Hypertensive disorders of pregnancy (HDP) affect foetal outcome. Labetalol is frequently used to lower maternal blood pressure and prolong pregnancy. Conflicting evidence exists for specific neonatal side effects described after maternal labetalol treatment. Our aim was to investigate neonatal effects of foetal exposure to labetalol on cerebral oxygenation and extraction., Methods: In a prospective observational study, clinical characteristics, vital parameters and cerebral oxygen delivery and extraction were collected during the first 24 h of life in labetalol-exposed preterm neonates and compared with two control groups., Results: Twenty-two infants with a mean gestational age of 28.9 weeks, born from labetalol-treated mothers with HDP were included and matched with 22 infants with non-labetalol-treated mothers with HDP and 22 infants without maternal HDP. No significant differences between groups were found neither in heart rate, blood pressure and inotropic support, nor in mean regional cerebral oxygen saturation and fractional tissue oxygen extraction., Conclusion: Foetal labetalol exposure associated effects on preterm heart rate, blood pressure, cerebral oxygenation and extraction are not demonstrated. Maternal disease severity seems to play a more important role in neonatal cerebral haemodynamics. Maternal labetalol treatment has no clinically important short term side effects in the preterm neonate.

The study was performed to assess the response & side effects of injectable Labetalol in the treatment of pregnancy induced severe hypertension. This interventional study was carried out on 72 patients having pregnancy induced severe hypertension attended in the Department of Obstetrics & Gynaecology, Mymensingh Medical College & Hospital (MMCH), Mymensingh, Bangladesh from November 2009 to October 2010. All patients were treated with intravenous Labetalol 20mg & the dose was repeated at sequential escalating dosages every 15 minutes until a therapeutic goal of systolic blood pressure <160mm of Hg & diastolic blood pressure <105mm of Hg were achieved. Among 72 respondents highest number were observed having systolic blood pressure 160-169 and 180 & above mm of Hg. The mean systolic & the diastolic blood pressure at the initiation of the study were observed 198±13.17mm of Hg & 119±8.6mm of Hg respectively. After use of injection Labetalol mean systolic blood pressure were 138.61±15.43mm of Hg, which is statistically significant (p value <0.001) & mean diastolic blood pressure were 96.18±9.7mm of Hg, which is also statistically significant (p value <0.001). It was observed that majority patients' blood pressure was controlled by 1-2 doses. It was noticed that injection Labetalol controls blood pressure in 80% antenatal cases & 86% postnatal cases. Out of 72 patients 4 cases (5.5%) experienced nausea & vomiting and only 1 case (1.1%) experienced headache. Regarding fetal outcome 48% patients delivered healthy baby, about 31% patients delivered asphyxiated baby & neonatal death were noticed in 4% cases. This study assessing the response & side effects of intravenous antihypertensive drug in the treatment of pregnancy induced severe hypertension shows that Labetalol fulfils the criteria of an antihypertensive drug for this purpose.

Objective: To determine whether the incidence of hypotension or adverse fetal heart tracing (FHT) category change differed following antepartum administration of intravenous (IV) labetalol versus hydralazine., Methods: Blood pressure and FHT categories were assessed one hour before and after medication administration. Hypotension was defined as ≥30% reduction in baseline systolic blood pressure (SBP) or SBP <90 mmHg. Changes in mean arterial pressure (MAP) were also compared. The National Institute for Child Health and Human Development (NICHD) three-tier category system was used to describe the FHT. For all category II tracings, Parer and Ikeda's system was also used., Results: Sixty-nine women received hydralazine and 31 women received labetalol during the study period. The incidence of hypotension (≥30% reduction in SBP) was similar between the labetalol (10%) and hydralazine (11%) groups (p = 0.98). No women experienced post-treatment SBP <90 mmHg. No association was observed between fetal heart rate category change and drug used. No women required emergent delivery for fetal indications., Conclusions: The incidence of maternal hypotension was low and did not differ following antepartum IV labetalol versus hydralazine use. These data should reassure providers about the use of parenteral labetalol and hydralazine for the treatment of severe hypertension.

The prevalence of hypertensive disorders in pregnancy is increasing. The etiology and pathophysiology of hypertensive disorders in pregnancy remain poorly understood. Hypertensive disorders are a major cause of maternal and perinatal morbidity and mortality. Treatment of hypertension decreases the incidence of severe hypertension, but it does not impact rates of preeclampsia or other pregnancy complications. Several antihypertensive medications are commonly used in pregnancy, although there is a lack of randomized controlled trials. Severe hypertension should be treated immediately to prevent maternal end-organ damage. Appropriate antepartum, intrapartum, and postpartum management is important in caring for patients with hypertensive disorders., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Case Description: Hyperkalemia can cause altered cardiac electrical conduction resulting in death. We describe a case of a 23-year old pregnant patient who presented with severe epigastric pain and vomiting. She was severely pre- eclamptic and received initial treatment with intravenous labetalol and decision was taken to deliver. She quickly became hyperkalaemic (serum potassium level 6.4 mmol/L) and labetalol was discontinued and intravenous hydralazine commenced. Post-surgery, her potassium levels were normal but due to rapidly rising blood pressure labetalol was recommenced, resulting in elevated potassium levels. Labetolol was discontinued, hydralazine prescribed, and potassium levels normalised. The adverse reaction was classified as 'probably' due to labetolol using the Naranjo Adverse Drug Reaction scale., Conclusion: This is the first reported case of labetolol induced hyperkalaemia in pregnancy, with life threatening consequences and hence all health professionals should be alert to this potential effect.

Objective: Labetalol and methyldopa are the two antihypertensive drugs most frequently used to control blood pressure for hypertensive disorders of pregnancy. The objective of this study was to assess if labetalol is associated with poor infant outcomes., Study Design: Retrospective population-based cohort study using the linked maternal/infant databases in the Province of Saskatchewan. Women with a diagnosis of a hypertensive disorder of pregnancy who delivered a singleton in Saskatchewan from January 1, 1990 to December 31, 2005 and who were dispensed only labetalol or only methyldopa were included in the study. Occurrences of small for gestational age (SGA)<10th percentile, SGA<3rd percentile, preterm birth, stillbirth, hospitalization for respiratory distress syndrome (RDS), sepsis, and seizure during infancy, and infant death were compared. Multiple logistic regression analysis was performed to adjust for potential confounding., Results: A total of 1223 eligible women were included in the final analysis. Among them, 300 received labetalol only and 923 received methyldopa only during pregnancy. For women with chronic hypertension, the rate of hospitalization for RDS, sepsis, and seizure during infancy was significantly higher for infants born to mothers who were dispensed labetalol only as compared with infants born to mothers who were dispensed methyldopa only (adjusted odds ratio (OR) 1.51, 95% confidence interval (CI) 1.02-2.22)., Conclusion: Compared with methyldopa, the use of labetalol for chronic hypertension of pregnancy may be associated with increased rate of hospitalization during infancy., (Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)

Objective: Hypertensive disorders in pregnancy remain a major cause of maternal morbidity and mortality. Blood pressure control is essential for maternal and neonatal outcome. Therefore, we analyzed the potency and side effects of two treatment options (nicardipine compared to labetalol) in order to gain insight in improved treatment of severe hypertension during pregnancy and to evaluate the feasibility of a randomised controlled trial., Study Design: A nested case control study in an inner city teaching hospital alongside a meta-analysis. Data from women who received nicardipine were compared with patients who received labetalol during pregnancy. Primary outcome measure was successful control of severe hypertension. Secondary outcome measures were maternal and neonatal side effects. These results were included in a meta-analysis., Results: Only one previous study described nicardipine in comparison to labetalol during pregnancy. The combined results indicate a similar success-rate of treatment with nicardipine compared to labetalol during pregnancy. Women treated with nicardipine had more often tachycardia, headache and nausea compared to women treated with labetalol. Hypotension resulting in fetal distress was found more often in the labetalol group., Conclusion: Nicardipine is a potent drug to control hypertension during pregnancy with side effects including maternal headaches, nausea and tachycardia. Labetalol had more neonatal side effects including hypotension compared with nicardipine. These results support the justification and prove that it is safe to perform a randomized controlled trial comparing nicardipine to labetalol in the treatment of severe hypertension in pregnancy.

Objective: To compare the effectiveness of orally administered nifedipine and intravenously administered labetalol for acute blood pressure control in hypertensive emergency of pregnancy., Methods: In this double-blind, randomized, controlled trial, pregnant women with sustained increase in systolic blood pressure of 160 mm Hg or higher or diastolic blood pressure of 110 mm Hg or higher were randomized to receive nifedipine (10 mg tablet orally up to five doses) and intravenous placebo saline injection or intravenous labetalol injection in escalating doses of 20, 40, 80, 80, and 80 mg and a placebo tablet every 20 minutes until the target blood pressure of 150 mm Hg systolic and 100 mm Hg diastolic, or lower, was achieved. Crossover treatment was administered if the initial treatment failed. The primary endpoint of the study was time necessary to achieve target blood pressure. Secondary endpoints were number of dosages required, adverse maternal and neonatal effects, side effect profile, and perinatal outcome., Results: From October 2012 to April 2013, we enrolled 60 patients. The median time taken to achieve target blood pressure was 40 minutes (interquartile range, 20-60 minutes) compared with 60 minutes (interquartile range 40-85 minutes) for nifedipine and labetalol, respectively (P=.008). The median dose required was two (interquartile range 1-3) compared with three (interquartile range 2-4.25) for nifedipine and labetalol, respectively (P=.008). No serious adverse maternal or perinatal side effects were witnessed in either group., Conclusion: As administered in this trial, oral nifedipine lowered blood pressure more quickly than did intravenous labetalol during hypertensive emergency in pregnancy., Clinical Trial Registration: Clinical Trials Registry-India, www.ctri.nic.in, CTRI/2013/02/003350., Level of Evidence: I.

Introduction: Acute hypertension is common following stroke and contributes to poor outcomes. Labetalol and nicardipine are often used for acute hypertension but there are little data comparing the two. This study is to evaluate the therapeutic response and tolerability of these two agents following acute stroke., Methods: This is a prospective, pseudo-randomized study comparing labetalol and nicardipine for blood pressure (BP) management in acute stroke patients. Patients who presented to the emergency department (ED) with confirmed hemorrhagic or ischemic stroke received either labetalol or nicardipine for 24 h from ED admission. Therapeutic response was assessed by achievement of goal BP, time spent within goal, and variability in BP. Clinical outcomes including length of stay, clinical status at discharge, and in-hospital mortality were recorded., Results: 54 patients were enrolled (labetalol = 28; nicardipine = 26) with 25 ± 6 BP measurements per patient. Majority of patients had a hemorrhagic stroke and baseline characteristics were similar between groups. All patients who received nicardipine achieved goal BP compared to 17 (61 %) in the labetalol group (p < 0.001) with 89 % nicardipine-treated patients achieved goal BP within 60 min of drug initiation versus 25 % in labetalol group (p < 0.001). Nicardipine group had better maintenance of BP, a greater percentage of time spent within goal, and significantly less BP variability compared to labetalol group (p < 0.001). Less rescue antihypertensive agents were given to nicardipine group than labetalol group (p < 0.001). The incidences of adverse drug events were similar between groups and there were no differences in clinical outcomes., Conclusion: In acutely hypertensive stroke patients, superior therapeutic response was achieved with nicardipine versus labetalol. Despite this, there was no demonstrable difference in clinical outcomes.

Objective: To determine whether maternal antihypertensive drugs influenced cerebral oxygenation in preterm infants during the first days after birth., Methods: We included 49 preterm infants (median gestational age 30.3 weeks, (range 26.0-31.9), birth weight 1250 g (560-2250)). Regional cerebral oxygen saturation (rcSO2) was measured by near-infrared spectroscopy on postnatal days 1, 2, 3, 4 and 5. Fractional tissue oxygen extraction (FTOE) was calculated using rcSO2 and arterial oxygen saturation (SpO2) values:(SpO2 - rcSO2)/SpO2., Results: Nine mothers were treated with labetalol and/or MgSO4 during pregnancy, three mothers with labetalol, MgSO4 and nifedipine, and 19 mothers with nifedipine only. Eighteen infants served as controls. Multivariate linear regression analysis showed that exposure to labetalol and/or MgSO4 during pregnancy decreased FTOE on day 1 after birth, while nifedipine did not., Conclusions: Treating pregnant women with labetalol and/or MgSO4 may influence cerebral oxygen extraction in their offspring shortly after birth.

Raynaud's phenomenon of the nipple is an unusual cause of severe nipple pain. Precipitants for Raynaud's phenomenon of the nipple are known to be cold temperatures, caffeine, and emotional stress. Nipple pain is quoted as the most common cause of cessation of breastfeeding. It is important that lactation consultants and other health care professionals are aware of Raynaud's phenomenon of the nipple and the treatment options available. This is a case of a 37-year-old woman, Gravida 2, Para 1, who was first seen in the antenatal clinic at 34 weeks gestation. A diagnosis of Raynaud's phenomenon of the nipple was made after she began taking labetalol for pregnancy-induced hypertension. The phenomenon had occurred in both of her previous pregnancies on commencing labetalol and resolved postnatally on cessation of the drug. We aim to raise awareness of both the condition itself and the potential role of labetalol in the development of Raynaud's phenomenon of the nipple.

Objective: We hypothesized that labetalol and pindolol have no detrimental effects on fetal cardiac function and pulmonary hemodynamics when administered for norepinephrine-induced maternal hypertension in a chronic sheep model of increased placental vascular resistance. Specifically, we investigated the effects of labetalol and pindolol on fetal cardiopulmonary responses to acute hypoxemia., Study Design: Twenty chronically instrumented near-term ewes with increased placental vascular resistance after placental embolization were anesthetized and randomized to receive labetalol or pindolol for norepinephrine-induced hypertension. Thereafter, maternal inspiratory oxygen fraction was decreased to induce fetal hypoxemia. At the end of each phase, fetal hemodynamics were assessed by Doppler ultrasonography. The data were analyzed using repeated measures ANOVA., Results: Maternal administration of norepinephrine had no effect on fetal hemodynamics. Pindolol decreased fetal heart rate and weight-indexed left ventricular cardiac output and increased pulmonary vascular impedances, while labetalol had no effect on these parameters. During hypoxemia, fetal heart rate increased to baseline in the pindolol group and pulmonary vascular impedances increased in the labetalol group, with no changes in fetal cardiac outputs., Conclusion: Pindolol decreased fetal left ventricular cardiac output and induced vasoconstriction in the pulmonary vasculature, but neither pindolol nor labetalol significantly modified fetal cardiopulmonary responses to acute hypoxemia., (Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.)

Background: Critically ill patients with acute hypertension often require titratable rapid blood pressure (BP) reductions using parenteral administration of drugs. There are few comparative studies available to make informed drug product selection decisions. The purpose of this study was to evaluate the short-term clinical outcomes and costs of intravenous labetalol or intravenous nicardipine in the management of hypertension in critically ill patients., Methods: This study was a retrospective analysis of consecutive patients receiving intravenous labetalol or intravenous nicardipine in the intensive care unit with acute elevations in either systolic (>160 mm Hg) or diastolic (>90 mm Hg) BP. Patient demographics, clinical characteristics, and short-term clinical outcomes were abstracted from the medical record. Hospital costs were calculated from hospital billing forms., Results: A total of 189 patients receiving labetalol and 193 patients receiving nicardipine were included in the analysis. The average hourly dose was 37.3 ± 9.4 mg/h for labetalol compared with 7.1 ± 5.6 mg/h for nicardipine (P < .001). The average total dose of labetalol was 170.9 ± 32.6 mg compared with 112.2 ± 29.1 mg for nicardipine (P = .02). The duration of therapy was significantly shorter for labetalol (8.2 ± 6.2 hours) compared with nicardipine (15.8 ± 4.4 hours) (P = .03). There were a greater number of dose titrations with labetalol (6.1 ± 6.2) than with nicardipine (4.7 ± 4.9), but this difference was not significantly different (P = .29). There were no significant differences in the magnitude of the average change in systolic (P = .79) or diastolic (P = .82) BP between labetalol and nicardipine. The proportion of patients achieving their BP targets was significantly greater with nicardipine (83%) than with labetalol (67%) (P = .04). The proportion of patients requiring an alternate antihypertensive agent was significantly greater with labetalol than with nicardipine (31% vs 17%; P = .02). The total number of all-cause adverse events was significantly greater with labetalol (61%) than with nicardipine (48%) (P = .04). Labetalol was associated with a significantly greater incidence of hypotension and bradycardia or atrioventricular block compared with nicardipine. There was no significant difference in the frequency of other adverse events between these 2 drugs. The median hospital costs were not significantly different between patients receiving labetalol and patients receiving nicardipine., Conclusion: Our study suggests that nicardipine is a more effective antihypertensive agent than labetalol in an unselected group of patients who develop hypertension in the intensive care unit setting. A major advantage of nicardipine compared with labetalol was fewer adverse effects. Nicardipine was associated with less hypotension and bradycardia or atrioventricular block, resulting in a lower rate of drug discontinuation compared with labetalol., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Objective: To assess the efficacy, side effects and perinatal outcome of nifedipine compared with other antihypertensives for treating severe preeclampsia in pregnant women., Methods: Randomized controlled trials (RCTs) that comparing nifedipine with other antihypertensives for severe preeclampsia were searched in PubMed, EMBase, Cochrane library, CNKI and VIP database etc(till January 2012). The quality of the included RCTs was evaluated, and Meta-analysis was performed with Rev Man 5.1 software., Results: Nine trials were included, involving 386 women in the nifedipine group, and 378 women in other antihypertensives group. Compared with other antihypertensives, nifidepine was associated with greater effective control of blood pressure (OR = 2.65, 95%CI: 1.65 - 4.25, P < 0.01). There was no clear difference in the time needed to control blood pressure (WMD = -3.64, 95%CI: -10.90 - 3.61, P = 0.32). Nifedipine could prolong gestation better than other antihypertensives (WMD = 5.14, 95%CI: 3.29 - 6.99, P < 0.01). There were no clear differences in maternal side effects headache (P = 0.28), palpitation (P = 0.06), and nausea vomiting (P = 0.28). No noticeable difference was found between the two groups in the Apgar score at five minutes (WMD = -0.21, 95%CI: -0.32 - 0.91, P = 0.72), neonatal respiratory distress syndrome (OR = 1.24, 95%CI: 0.57 - 2.67, P = 0.59), or perinatal deaths (OR = 0.49, 95%CI: 0.22 - 1.11, P = 0.09)., Conclusion: Nifedipine is associated with greater effective control of blood pressure and prolongation of gestation, with no additional neonatal respiratory distress syndrome or perinatal deaths, compared with other antihypertensives for women with severe preeclampsia.

Background: Pregnancy-induced hypertension (PIH) is associated with adverse fetal and maternal outcome. The role of medication to control blood pressure (BP) in mild to moderate PIH is controversial., Aims: We conducted a prospective study to investigate whether pharmacological treatment of mild to moderate PIH is effective in improving maternal and fetal outcomes., Methods: A total of 150 consecutive pregnant women without proteinuria and with physician-recorded systolic BP of 140-160 mmHg and/or diastolic BP of 90-105 mmHg on two occasions ≥6 h apart between 20 and 38 weeks of gestation were randomly allocated to receive either labetalol or methyldopa (50 patients each) plus standard care (treatment group) or only standard care (50 patients) (control group)., Results and Conclusions: As compared to the control group, the treatment group had lower rates of severe PIH (28% vs. 10%, P = 0.005), proteinuria (28% vs. 12%, P = 0.016), hospitalization before term (28% vs. 14%, P = 0.041), and delivery by cesarean section (38% vs. 22%, P = 0.042). In a multivariable logistic regression model that adjusted for maternal age, weight, parity, previous PIH, and baseline hemoglobin, resting heart rate, and BP levels, antihypertensive therapy was associated with a lower incidence of adverse maternal events (P = 0.011). Compared to the control group, the treatment group had lower incidence of SGA babies (40% vs. 23%, P = 0.033), preterm birth (36% vs. 14%, P = 0.002), and admission to neonatal unit (30% vs. 15%, P = 0.036). After adjustment for maternal age, weight, baseline hemoglobin, resting heart rate, BP level, parity and previous history of PIH, fetal death, preterm delivery or SGA baby, antihypertensive therapy was associated with a lower incidence of adverse perinatal events (P = 0.016). Maternal and perinatal mortality rates were not significantly different between treatment and control groups. In conclusion, pharmacological treatment of mild to moderate PIH is associated with lower rate of some maternal and fetal-neonatal non-fatal adverse events compared to no routine use of antihypertensive therapy.

A 42-year-old multigravida with severe pre-eclampsia had an emergency caesarean section under spinal anaesthesia. Peri-operatively, her arterial pressure was controlled with oral methyldopa and an intravenous infusion of labetalol. Postoperatively, in the Intensive Care Unit, she had recurrent episodes of hypoglycaemia which required treatment with intravenous glucose. These episodes resolved when the labetalol infusion was stopped. Clinicians should be aware of the potential of labetalol to cause hypoglycaemia.

Objective: To determine the efficacy and safety of labetalol for hypertensive crisis in children ≤ 24 months of age., Design: Retrospective chart review. Statistical analysis utilized analysis of variance for continuous data, chi-square tests for nominal data, and linear regression., Setting: A 737-bed pediatric teaching institution., Patients: Twenty-seven patients ≤ 24 months of age were treated with 37 intravenous infusions of labetalol, nicardipine, or nitroprusside for hypertensive crisis or hypertensive urgency., Interventions: None., Measurements and Main Results: The primary end point consisted of time to 20% reduction in systolic blood pressure. Primary safety end points measured the prevalence of deleterious effects of labetalol. Continuous infusion of labetalol reduced mean systolic blood pressure by at least 20% in < 8 hrs. This effect was similar to nicardipine and nitroprusside infusions. The reported side effects were similar in each group. Patients receiving labetalol and presenting with ischemic or traumatic brain injury were likely to develop hypotension requiring infusion discontinuation., Conclusions: Continuous intravenous labetalol infusion is efficacious for treatment of hypertensive crisis in children ≤ 24 months of age. Aside from patients presenting with ischemic or traumatic brain injury, labetalol was safe to use in this population for hypertensive emergencies and had a satisfactory adverse effect profile. Labetalol may reach dose saturation at a much lower dose in young children in comparison to adults. Clinicians should use caution when initiating labetalol infusions in young patients with brain injury.

Introduction: Our purpose was to compare the safety and efficacy of food and drug administration (FDA) recommended dosing of IV nicardipine versus IV labetalol for the management of acute hypertension., Methods: Multicenter randomized clinical trial. Eligible patients had 2 systolic blood pressure (SBP) measures ≥180 mmHg and no contraindications to nicardipine or labetalol. Before randomization, the physician specified a target SBP ± 20 mmHg (the target range: TR). The primary endpoint was the percent of subjects meeting TR during the initial 30 minutes of treatment., Results: Of 226 randomized patients, 110 received nicardipine and 116 labetalol. End organ damage preceded treatment in 143 (63.3%); 71 nicardipine and 72 labetalol patients. Median initial SBP was 212.5 (IQR 197, 230) and 212 mmHg (IQR 200,225) for nicardipine and labetalol patients (P = 0.68), respectively. Within 30 minutes, nicardipine patients more often reached TR than labetalol (91.7 vs. 82.5%, P = 0.039). Of 6 BP measures (taken every 5 minutes) during the study period, nicardipine patients had higher rates of five and six instances within TR than labetalol (47.3% vs. 32.8%, P = 0.026). Rescue medication need did not differ between nicardipine and labetalol (15.5 vs. 22.4%, P = 0.183). Labetalol patients had slower heart rates at all time points (P < 0.01). Multivariable modeling showed nicardipine patients were more likely in TR than labetalol patients at 30 minutes (OR 2.73, P = 0.028; C stat for model = 0.72), Conclusions: Patients treated with nicardipine are more likely to reach the physician-specified SBP target range within 30 minutes than those treated with labetalol.

Objective: To determine the functional development of children born after treatment of mild-to-moderate gestational hypertension with labetalol versus methyldopa, and no antihypertensive treatment., Design: Historical cohort study., Setting: Twelve Dutch hospital departments of obstetrics., Population: Live-born children born in these hospitals and prenatally exposed to labetalol, methyldopa, or bed rest because of mild-to-moderate gestational hypertension., Methods: Central nervous system development was measured with standard tests at 4-10 years of age. Linear regression techniques and Pearson's chi-square tests were used to compare the groups with regard to the outcome measures., Main Outcome Measures: Intelligence quotient (IQ), concentration, motor development, and behaviour at primary school age., Results: A total of 202 children were included in the analyses. More children exposed to labetalol had attention deficit hyperactivity disorder (ADHD) than those exposed to methyldopa (OR 2.3; 95% CI 0.7-7.3), or those born to women who had been admitted for bed rest (OR 4.1; 95% CI 1.2-13.9). Sleeping problems seemed to be reported more frequently after prenatal methyldopa exposure than after exposure to labetalol (OR 3.2; 95% CI 0.6-16.7) or bed rest (OR 4.5; 95% CI 0.9-23.2), although the differences were not statistically significant. Test scores on other aspects of functional development did not differ between the three groups., Conclusions: In this hypothesis-generating study, labetalol exposure in utero seemed to increase the risk of ADHD among children of primary school age, whereas prenatal methyldopa exposure might influence sleep. Further studies with appropriate sample sizes are warranted to determine the long-term effects of antihypertensive medications.

We investigated the effects of labetalol and pindolol on uterine, placental, and fetal hemodynamics following norepinephrine-induced maternal hypertension in a sheep model of increased placental vascular resistance. Also, we examined fetal and placental hemodynamic responses to acute hypoxemia after antihypertensive medication. Norepinephrine increased maternal heart rate (HR), mean arterial pressure (MAP) and uterine vascular resistance (R(UtA)), and decreased uterine volume blood flow (Q(UtA)). Both labetalol and pindolol decreased maternal HR, MAP, and R(UtA), but did not restore Q(UtA). Fetal MAP was unaffected while fetal HR and placental volume blood flow (Q(UA)) decreased and placental vascular resistance increased. During hypoxemia, which was induced by decreasing maternal inspiratory oxygen fraction, all these parameters remained unchanged in the labetalol group while fetal HR increased and Q(UA) further decreased in the pindolol group. We conclude that labetalol and pindolol may compromise uterine and placental hemodynamics. Hypoxemic stress provokes divergent hemodynamic responses in fetuses exposed to these differently acting adrenoceptor antagonists.

Background: Raised blood pressure is common after acute stroke and is associated with an adverse prognosis. We sought to assess the feasibility, safety, and effects of two regimens for lowering blood pressure in patients who have had a stroke., Methods: Patients who had cerebral infarction or cerebral haemorrhage and were hypertensive (systolic blood pressure [SBP] >160 mm Hg) were randomly assigned by secure internet central randomisation to receive oral labetalol, lisinopril, or placebo if they were non-dysphagic, or intravenous labetalol, sublingual lisinopril, or placebo if they had dysphagia, within 36 h of symptom onset in this double-blind pilot trial. The doses were titrated up if target blood pressure was not reached. Analysis was by intention to treat. This trial is registered with the National Research Register, number N0484128008., Findings: 179 patients (mean age 74 [SD 11] years; SBP 181 [SD 16] mm Hg; diastolic blood pressure [DBP] 95 [SD 13] mm Hg; median National Institutes of Health stroke scale [NIHSS] score 9 [IQR 5-16] points) were randomly assigned to receive labetolol (n=58), lisinopril (n=58), or placebo (n=63) between January, 2005, and December, 2007. The primary outcome--death or dependency at 2 weeks--occurred in 61% (69) of the active and 59% (35) of the placebo group (relative risk [RR] 1.03, 95% CI 0.80-1.33; p=0.82). There was no evidence of early neurological deterioration with active treatment (RR 1.22, 0.33-4.54; p=0.76) despite the significantly greater fall in SBP within the first 24 h in this group compared with placebo (21 [17-25] mm Hg vs 11 [5-17] mm Hg; p=0.004). No increase in serious adverse events was reported with active treatment (RR 0.91, 0.69-1.12; p=0.50) but 3-month mortality was halved (9.7%vs 20.3%, hazard ratio [HR] 0.40, 95% CI 0.2-1.0; p=0.05)., Interpretation: Labetalol and lisinopril are effective antihypertensive drugs in acute stroke that do not increase serious adverse events. Early lowering of blood pressure with lisinopril and labetalol after acute stroke seems to be a promising approach to reduce mortality and potential disability. However, in view of the small sample size, care must be taken when these results are interpreted and further evaluation in larger trials is needed.

Background: The optimal blood pressure (BP) for treating acute intracerebral hemorrhage remains (ICH) uncertain. High BP may contribute to hematoma growth while excessive BP reduction might precipitate peri-hemorrhage ischemia. We examine here the feasibility and safety of reducing BP to lower than presently recommended levels in patients with acute ICH., Methods: Patients with ICH were prospectively randomized to standard BP treatment (mean arterial BP [MAP] 110-130 mmHg) or aggressive BP lowering (MAP < 110 mmHg) within 8 h of symptom onset. MAP was managed during the 48 h treatment period. NIHSS was obtained at baseline, 24, and 48 h. Brain CT was done 24 h after symptoms. A modified Rankin Scale (mRs) was obtained at 90 days. A clinical decline (NIHSS drop > or = 2 points) within the first 48 h was the primary endpoint. Hematoma enlargement at 24 h was a secondary endpoint., Results: We enrolled 21 patients into each group. Mean age was 60.6 +/- 12.3 years and MAP on presentation was 147.6 +/- 18.2 mmHg. Treatment was started on average 3.2 +/- 2.2 h after symptom onset. Baseline clinical variables were identical between the 2 treatment groups. Target blood pressure was achieved within 87.1 +/- 59.6 min in the standard group and 163.5 +/- 163.8 min in the aggressive BP treatment group. There were no significant differences in early neurological deterioration, hematoma and edema growth, and clinical outcome at 90 days., Conclusion: A more aggressive reduction of acute hypertension after ICH does not increase the rate of neurological deterioration even when treatment is initiated within hours of symptom onset. Lowering BP aggressively did not affect hematoma and edema expansion but this possibility deserves further study.

Purpose: Labetalol is an effective antihypertensive medication frequently used to treat systemic hypertension in acute care settings, including the management of hypertension associated with a subarachnoid hemorrhage. We present a case of profound hypotension, refractory to inotropic and vasopressor therapy following an iv infusion of labetalol., Clinical Features: Initiation of an iv labetalol infusion resulted in good blood pressure control in a patient suffering from a Fisher grade 3 subarachnoid hemorrhage with an initial Glascow coma scale of 14/15 and mild hydrocephalus. Progressive deterioration of neurological symptoms and evidence of worsening hydrocephalus preceded the sudden development of profound hypotension (60/35 mmHg) and bradycardia with a minimum heart rate of 40 beats.min(-1). Initial resuscitative efforts included administration of intravascular fluid, hypertonic saline, atropine, adrenalin (more than 10 mg in divided doses) and noradrenalin. These measures restored the blood pressure to 80/45 with a HR of 98 beats.min(-1). Intraoperative placement of an intraventricular drain released cerebrospinal fluid under pressure with an initial intracranial pressure of 15 cm H(2)O. A combination of adrenalin, noradrenalin, dopamine and vasopressin infusions were required to restore the blood pressure to 130/65 mmHg after an additional two hours. All inotropic and vasopressor support was weaned off after the 14th hr (about two drug half-lives). The patient was awake and responsive the following day, with no obvious neurological consequences. No evidence of neurological injury, drug administration error or myocardial dysfunction was documented., Conclusion: The episode of profound hypotension which occurred after initiating a labetolol infusion required maximal combined vasopressor therapy to restore the blood pressure suggesting that this patient demonstrated an extreme sensitivity to labetalol. Combination therapy with adrenergic and nonadrenergic agonists may be required for optimal treatment of profound hypotension associated with labetalol-induced vasoplegia.

As community hospitals adopt comprehensive stroke pathways, nurses in critical care areas must prepare for each possible complication. Although the thrombolytic component of a new stroke protocol may receive the most attention, the various details of the pathway--in this case, management of blood pressure--should not be overlooked. Critical care nurses who appreciate the considerations for treatment of hypertension and who can correctly and efficiently administer intravenous labetalol may save precious time and enhance outcomes for patients with stroke who have hypertension.

Implications: Although recent Food and Drug Administration warnings have noted proarrhythmic effects of droperidol, other antiemetic drugs may have similar effects. We report a case of cardiac arrest after uncomplicated regional anesthesia in a patient with scleroderma who received labetalol and metoclopramide after surgery. Metoclopramide should be used with caution when risk factors for dysrhythmia are present.

Background: Labetalol is a commonly used agent for perioperative hypertension in renal transplant recipients. A previous report suggested that labetalol may cause life-threatening hyperkalemia after renal transplantation., Methods: We performed a retrospective review of 103 consecutive renal transplants to determine whether labetalol was an independent predictor of hyperkalemia treatment. Thirty-eight patients (36.9%) received labetalol, and 65 patients (63.1%) had no labetalol medication., Results: Of the 103 patients, 24 (23.3%) required treatment for hyperkalemia. Thirteen (34.2%) of the patients who had labetolol medication and 11 (16.9%) of the patients who did not receive labetalol were treated for hyperkalemia (p = 0.045). Factors considered for a logistic regression model included: the use of labetalol, cold ischemia time, diabetes, and dialysis method; intake of tacrolimus, beta blockers, angiotensin-converting enzyme inhibitors, or other antihypertensives prior to admission; the mannitol dose given intraoperatively, and the 24-hour urine output postoperatively. Intravenous labetalol (odds ratio OR = 4.52, confidence interval CI = 1.33-15.28; p = 0.02), 24- hour urine output (OR = 4.4, CI = 0.97-20.1: p = 0.47), increasing cold ischemia time (OR = 1.09, CI = 1.01-1.17; p = 0.02), and continuous ambulatory peritoneal dialysis (OR = 0.17, CI = 0.29-0.98; p = 0.036) were independent predictors., Conclusion: Labetalol appears to increase the risk of hyperkalemia in patients after renal transplantation., (Copyright 2002 S. Karger AG, Basel)

Drug-induced hepatotoxicity is an important cause of hepatocellular injury. Hepatic necrosis may range from asymptomatic elevations in transaminases to fulminant hepatic failure and death. A 50-year-old Asian man developed moderate elevations of hepatic transaminases after commencing labetalol therapy for a hypertensive cerebral hemorrhage. Extensive evaluation revealed evidence of chronic hepatitis B infection, of which the patient was previously not aware. Hepatic transaminases normalized after discontinuation of labetalol., ((c)2002 Le Jacq Communications, Inc.)