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Introduction: Hypertensive disorders during pregnancy elevate the likelihood of unfavorable outcomes for both mother and fetus. In cases of acute hypertension, several pharmacological interventions are available to lower blood pressure, such as hydralazine, a direct arteriolar vasodilator, and labetalol, a combined alpha and beta-blocker., Objectives: This systematic review and meta-analysis of randomized controlled trials (RCTs) aims to compare the efficacy and safety of intravenous labetalol and intravenous hydralazine for acute hypertensive disorders during pregnancy., Methods: We systematically searched PubMed, Embase and Cochrane for studies comparing labetalol versus hydralazine in pregnant patients. The primary outcomes were median arterial blood pressure (MABP), diastolic blood pressure (DBP) and systolic blood pressure (SBP). We performed statistical analyses using R 4.1.1. Heterogeneity was examined with the Cochran Q test and I 2 statistics. Risk ratios (RR) and mean differences (MD) with 95% confidence intervals (CI), were computed with a random-effects model., Results: Nineteen RCTs were included in this meta-analysis, comprising 2,261 patients. Among them, 1,131 (50 %) received treatment with labetalol. There was no statistically significant difference between groups in terms of SBP (MD -1.74; 95 % CI -6.72 to 3.23; p = 0.49; I 2  = 93 %), MABP (MD -0.72; 95 % CI -2.34 to 0.90; p = 0.39; I 2  = 0 %), DBP (MD 0.25; 95 % CI -4.72 to 5.21; p = 0.92; I 2  = 96 %), tachycardia (RR 0.42; 95 % CI 0.15 to 1.18; p = 0.099; I 2  = 41 %), and placenta abruption (RR 0.42; 95 % CI 0.15 to 1.16; p = 0.093; I 2  = 0 %). However, labetalol significantly reduced maternal hypotension (RR 0.26; 95 % CI 0.21 to 0.33; p < 0.001; I 2  = 41 %) compared with hydralazine., Conclusion: This systematic review and meta-analysis of RCTs found that labetalol and hydralazine were efficient for hypertension disorders in pregnancy. However, labetalol reduced the incidence of maternal hypotension., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

As detailed information on the pharmacokinetics (PK) of labetalol in pregnant people are lacking, the aims of this study were: (1) to build a physiologically based PK (PBPK) model of labetalol in non-pregnant individuals that incorporates different CYP2C19 genotypes (specifically, *1/*1, *1/*2 or *3, *2/*2, and *17/*17); (2) to translate this model to the second and third trimester of pregnancy; and (3) to combine the model with a previously published direct pharmacodynamic (PD) model to predict the blood pressure lowering effect of labetalol in the third trimester. Clinical data for model evaluation was obtained from the scientific literature. In non-pregnant populations, the mean ratios of simulated versus observed peak concentration (C max ), time to reach C max (T max ), and exposure (area under the plasma concentration-time curve, AUC) were 0.94, 0.82, and 1.16, respectively. The pregnancy PBPK model captured the observed PK adequately, but clearance was slightly underestimated with mean ratios of simulated versus observed C max , T max , and AUC of 1.28, 1.30, and 1.39, respectively. The results suggested that pregnant people with CYP2C19 *2/*2 alleles have similar labetalol exposure and trough levels compared to non-pregnant controls, whereas those with other alleles were found to have increased exposure and trough concentrations. Importantly, the pregnancy PBPK/PD model predicted that, despite increased exposure in some genotypes, the blood pressure lowering effect was broadly comparable across all genotypes. In view of the large inter-individual variability and the potentially increasing blood pressure during pregnancy, patients may need to be closely monitored for achieving optimal therapeutic effects and avoiding adverse events., (© 2024, The American College of Clinical Pharmacology.)

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.)

Anaesthesiologists commonly use intravenous labetalol to adjust patient haemodynamics during surgical procedures. Cases of profound hypotension after continuous labetalol infusions have been reported; however, there is limited evidence regarding the safety of intraoperative labetalol boluses. This audit examined the frequency of postoperative hypotension and bradycardia in 292 adult non-cardiac surgery patients treated with intraoperative labetalol boluses. Blood pressure and heart rate data were collected from the post-anaesthesia care unit and on the floor units for 24 hours after surgery. The median total intraoperative labetalol dose was 10mg. A total of 30/292 patients had all-cause postoperative hypotension within 24 hours of surgery, 26 of which had other medical or surgical precipitants. Fifteen patients developed bradycardia. There were no deaths or intensive care unit admissions attributed to labetalol. This audit demonstrates a low risk of all-cause postoperative hypotension (10%) and bradycardia (5%) after the use of small IV doses of intraoperative labetalol.

Background: Despite major advances in the pharmacologic treatment of hypertension in the nonpregnant population, treatments for hypertension in pregnancy have remained largely unchanged over the years. There is recent evidence that a more adequate control of maternal blood pressure is achieved when the first given antihypertensive drug is able to correct the underlying hemodynamic disorder of the mother besides normalizing the blood pressure values., Objective: This study aimed to compare the blood pressure control in women receiving an appropriate or inappropriate antihypertensive therapy following the baseline hemodynamic findings., Study Design: This was a prospective multicenter study that included a population of women with de novo diagnosis of hypertensive disorders of pregnancy. A noninvasive assessment of the following maternal parameters was performed on hospital admission via Ultrasound Cardiac Output Monitor before any antihypertensive therapy was given: cardiac output, heart rate, systemic vascular resistance, and stroke volume. The clinician who prescribed the antihypertensive therapy was blinded to the hemodynamic evaluation and used as first-line treatment a vasodilator (nifedipine or alpha methyldopa) or a beta-blocker (labetalol) based on his preferences or on the local protocols. The first-line pharmacologic treatment was retrospectively considered hemodynamically appropriate in either of the following circumstances: (1) women with a hypodynamic profile (defined as low cardiac output [≤5 L/min] and/or high systemic vascular resistance [≥1300 dynes/second/cm 2 ]) who were administered oral nifedipine or alpha methyldopa and (2) women with a hyperdynamic profile (defined as normal or high cardiac output [>5 L/min] and/or low systemic vascular resistances [<1300 dynes/second/cm 2 ]) who were administered oral labetalol. The primary outcome of the study was to compare the occurrence of severe hypertension between women treated with a hemodynamically appropriate therapy and women treated with an inappropriate therapy., Results: A total of 152 women with hypertensive disorders of pregnancy were included in the final analysis. Most women displayed a hypodynamic profile (114 [75.0%]) and received a hemodynamically appropriate treatment (116 [76.3%]). The occurrence of severe hypertension before delivery was significantly lower in the group receiving an appropriate therapy than in the group receiving an inappropriately treated (6.0% vs 19.4%, respectively; P=.02). Moreover, the number of women who achieved target values of blood pressure within 48 to 72 hours from the treatment start was higher in the group who received an appropriate treatment than in the group who received an inappropriate treatment (70.7% vs 50.0%, respectively; P=.02)., Conclusion: In pregnant individuals with de novo hypertensive disorders of pregnancy, a lower occurrence of severe hypertension was observed when the first-line antihypertensive agent was tailored to the correct maternal hemodynamic profile., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

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., (Copyright © 2024 Associação Brasileira de Otorrinolaringologia e Cirurgia Cérvico-Facial. Published by Elsevier España S.L.U. All rights reserved.)

Objectives: To investigate the effects of intravenous nicardipine as initial therapy and oral labetalol combined with nifedipine controlled-release tablet as subsequent treatment of severe peripartum hypertension., Material and Methods: Intravenous nicardipine was delivered as the initial treatment, after the target blood pressure (BP) had been achieved, oral labetalol was used to maintain the target BP. If oral labetalol failed to maintain the target BP, oral labetalol combined with nifedipine controlled-release tablet was used., Results: A total number of 131 patients were enrolled. The target BP (BP < 140/90 mmHg) was achieved in all patients within 60 minutes by intravenous nicardipine. After receiving labetalol orally, the target BP was maintained in nine patients. However, in 104 patients, we had to combine oral labetalol and nifedipine controlled-release tablet due to re-elevation of their systolic BP to 140-159 mmHg. In 18 patients, we restarted intravenous nicardipine because their systolic BP re-elevated above 160 mm Hg. Among the 104 patients who received oral labetalol and nifedipine controlled-release tablet, the target BP was achieved and maintained in 96 patients, and eight patients had to restart nicardipine. Of the total number of 26 patients in whom intravenous nicardipine was resumed, the target BP was successfully maintained in 22 patients with oral labetalol combined with nifedipine controlled-release tablet., Conclusions: Intravenous nicardipine rapidly and safely lowered severe peripartum hypertension. As subsequent therapy, oral labetalol combined with nifedipine controlled-release tablet protocol may be applied to effectively maintain a target BP.

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.)

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Objective: To evaluate whether implementation of a semiautonomous treatment algorithm was associated with improved compliance with American College of Obstetricians and Gynecologists guidelines for rapid administration of antihypertensive therapy in the setting of sustained severe hypertension., Methods: This was a single-center retrospective cohort study of admitted pregnant and postpartum patients treated for severe hypertension between January 2017 and March 2020. The semiautonomous treatment algorithm, which included vital sign monitoring, blood pressure thresholds for diagnosis of severe hypertension, and automated order sets for recommended first-line antihypertensive therapy were implemented between May 2018 and March 2019. The primary outcomes were the administration of antihypertensive therapy within 15, 30 and 60 minutes of diagnosis of severe hypertension. Comparisons were made between the preimplementation, during implementation, and postimplementation groups using χ2. Analysis was limited to the first episode of severe hypertension treated. Statistical significance was defined as P<.05., Results: In total, there were 959 obstetric patients treated for severe hypertension, with 373 (38.9%) treated preimplementation, 334 (34.8%) during implementation, and 252 (26.2%) after implementation. Treatment of severe hypertension within 15 minutes was 36.5% preimplementation, 45.8% during implementation, and 55.6% postimplementation (P=.001). Treatment within 30 minutes was 65.9% in the preimplementation group, 77.8% during implementation, and 79.0% in the postimplementation group (P=.004). There was no difference in percentage of patients treated within 60 minutes (86.3% before, 87.7% during and 92.9% after implementation, P=.12)., Conclusion: Implementation of a semiautonomous treatment algorithm for severe hypertension was associated with a higher percentage of pregnant and postpartum patients receiving the first dose of antihypertensive therapy within 15 and 30 minutes. Implementation of similar algorithms for this and other obstetric indications may decrease time to appropriate therapy and help improve care equity., Competing Interests: Financial Disclosure The authors did not report any potential conflicts of interest., (Copyright © 2021 The Author(s). Published by Wolters Kluwer Health, Inc.)

Objective : This network meta-analysis (NMA) aimed to determine the relative efficacy and safety of pharmacological strategies used to mitigate haemodynamic instability by intubation for general anaesthesia in hypertensive parturient women undergoing caesarean section. Methods : We considered randomised controlled studies comparing the effects of pharmacological strategies used to alleviate haemodynamic instability during intubation in parturient women with hypertensive disorders of pregnancy. The primary endpoints were maximum blood pressure and heart rate after intubation, and secondary endpoints were the Apgar scores at 1 and 5 min. NMA allowed us to combine direct and indirect comparisons between strategies. Results : Twelve studies evaluating nine pharmacological strategies in 619 patients were included. According to the surface under the cumulative ranking curve, the maximal mean arterial pressure was lowest for high-dose remifentanil (99.4%) followed by nitroglycerin (73.6%) and labetalol (60.9%). The maximal heart rate was lowest for labetalol (99.9%) followed by high dose of remifentanil (81.2%) and fentanyl (61.6%). Apgar score at 1 min was higher with low-dose than with high-dose remifentanil (mean difference, 0.726; 95% confidence interval, 0.056 to 1.396; I 2 =0.0%). Conclusions : High-dose remifentanil produces minimum blood pressure changes, while labetalol is most effective in maintaining normal heart rate in parturient women with hypertensive disorders of pregnancy during caesarean section under general anaesthesia., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

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.)

Background: Previous evidence has demonstrated that serum leptin is correlated with appetite in combination with, but not without, modest exercise., Aim: The present experiments investigated the effects of exogenous adrenaline and α/β adrenoceptor blockade in combination with moderate exercise on serum leptin concentrations, appetite/satiety sensations and subsequent food intake in obese women., Methods: A total of 10 obese women ((mean ± SEM), age: 50 (1.9) years, body mass index 36 (4.1) kg/m 2 , waist 104.8 (4.1) cm) participated in two separate, double-blind randomised experimental trials. Experiment 1: moderate exercise after α/β adrenergic blocker (labetalol, 100 mg orally) versus moderate exercise plus placebo; experiment 2: adrenaline infusion for 20 minutes versus saline infusion. Appetite/satiety and biochemistry were measured at baseline, pre- and immediately post-intervention, then 1 hour post-intervention (i.e., before dinner). Food intake was assessed via ad libitum buffet-style dinner., Results: No differences were found in appetite/satiety, subsequent food intake or serum leptin in any of the studies (experiment 1 or experiment 2). In experiment 1, blood glucose was higher ( p < 0.01) and plasma free fatty acids lower ( p = 0.04) versus placebo. In experiment 2, plasma free fatty acids ( p < 0.05) increased after adrenaline versus saline infusion., Conclusions: Neither inhibition of exercise-induced adrenergic activity by combined α/β adrenergic blockade nor moderate increases in adrenergic activity induced by intravenous adrenaline infusion affected acute appetite regulation.

Background: Pregnant women with preeclampsia have been found to have elevated cerebral perfusion pressure and impaired cerebral autoregulation compared with normal pregnant women. Transcranial Doppler is a noninvasive technique used to estimate cerebral perfusion pressure. The effects of different antihypertensive medications on cerebral perfusion pressure in preeclampsia are unknown., Objective: To compare the change in cerebral perfusion pressure before and after intravenous labetalol vs oral nifedipine in the setting of acute severe hypertension in pregnancy., Study Design: This is a prospective cohort study of pregnant women between 24 and 42 weeks' gestation with severe hypertension (systolic blood pressure ≥160 mm Hg and/or diastolic blood pressure ≥110 mm Hg). Women who consented to the study and received either intravenous labetalol or oral nifedipine were included. Exclusion criteria included active labor or receipt of any antihypertensive medication within 2 hours of initial cerebral perfusion pressure measurement. Peripheral blood pressure and transcranial Doppler studies for middle cerebral artery hemodynamics were performed prior to the administration of antihypertensive medications and repeated 30 minutes after medication administration., Results: A total of 16 women with acute severe hypertension were enrolled; 8 received intravenous labetalol and 8 received oral nifedipine. There were no significant differences between the labetalol and nifedipine groups in baseline characteristics such as maternal age, race and ethnicity, payment, hospital site, body mass index, nulliparity, gestational age, preexisting diabetes mellitus or chronic hypertension, fetal growth restriction, magnesium sulfate administration, and symptomatology (P>.05). When examined 30 minutes after the administration of either intravenous labetalol or oral nifedipine, there was a significantly greater decrease in systolic blood pressure (-9.8 mm Hg vs -39 mm Hg; P=.003), mean arterial pressure (-7.1 mm Hg vs -22.3 mm Hg; P=.02), and cerebral perfusion pressure (-2.5 mm Hg vs -27.7 mm Hg; P=.01) in the nifedipine group. There was no statistically significant decrease in diastolic blood pressure (-12.9 mm Hg vs -5.4 mm Hg; P=.15). The change in middle cerebral artery velocity by transcranial Doppler was compared between the groups and was not different (0.07 cm/s vs 0.16 cm/s; P=.64)., Conclusion: Oral nifedipine resulted in a significant decrease in cerebral perfusion pressure, whereas labetalol did not, after administration for acute severe hypertension among women with preeclampsia. This decrease seems to be driven by a decrease in peripheral arterial blood pressure rather than a direct change in cerebral blood flow., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: To evaluate the effect on arterial blood pressure (ABP) of labetalol infusion as treatment for perioperative non nociceptive acute hypertension in dogs. The clinical records of dogs receiving intra or postoperative labetalol infusion were retrospectively reviewed. Invasive systolic (SAP), mean (MAP) and diastolic (DAP) arterial pressure and heart rate (HR) before labetalol infusion (T0) and 15, 30, 45 and 60 min (T1, T2, T3 and T4 respectively) after infusion were retrieved. The dose rate of labetalol infusion and use of concurrently administered drugs that could have potentially affected ABP and/or HR were also recorded. ANOVA for repeated measures and Dunnett's multiple comparison test were used to determine the effect of labetalol on ABP and HR. Differences were considered significant when p < 0.05., Results: A total of 20 dogs met the inclusion criteria, and hypertension was documented after craniotomy (12/20), adrenalectomy (4/20) and other procedures (4/20). Five dogs received labetalol intraoperatively, 14 postoperatively, and 1 during the surgical procedure and recovery. Median infusion duration and rate were 463 (60-2120) minutes and 1.1 (0.2-3.4) mg/kg/h respectively. Median loading dose was 0.2 (0.2-0.4) mg/kg. Labetalol produced a significant decrease in SAP and DAP at all time points compared to T0 (p < 0.05), while the effect was not significant at T1 for MAP (p = 0.0519). Median maximum MAP decrease was 31 (20-90) mmHg. Heart rate did not increase significantly during treatment (p = 0.2454). Acepromazine given before or during labetalol treatment did not reduce significantly ABP (p = 0.735)., Conclusions: Labetalol produced a reliable and titratable decrease in ABP with non significant increase in HR.

Objective: To study the maternal hemodynamic changes in acute severe hypertension after treatment with intravenous labetalol or oral nifedipine using color doppler ultrasound., Study Design: We evaluated thirty pregnant women with gestational age between 28 and 40 weeks in acute severe hypertension (more than or equal to 160/105 mmHg) which were randomly allocated to receive either intravenous labetalol or oral nifedipine until blood pressure was lowered to less than or equal to 140/90 mmHg. Doppler vascular indices namely pulsatility index, resistance index, S/D ratio of bilateral uterine arteries and maternal renal artery were measured baseline at the time of acute severe hypertension and repeated after control of blood pressure, to assess the changes in maternal hemodynamics if any with labetalol or nifedipine., Results: When evaluating right uterine artery Doppler parameters, a trend to increase in PI and RI was observed in those who received labetalol and nifedipine however the difference was not statistically significant. Whereas, while evaluating left uterine artery indices a trend to decrease PI was seen in nifedipine group but the difference was not statistically significant. On intergroup comparison there was no any significant change in any of uterine artery as well as renal artery indices in either group., Conclusion: The use of labetalol and nifedipine were not related to any significant changes in maternal Doppler, which is reassuring about the safety of these drugs when treating acute severe hypertension in pregnancy., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020. Published by Elsevier B.V.)

Objective: To explore the regulatory effect of magnesium sulfate combined with nifedipine and labetalol on disease-related molecules in serum and placenta in the treatment of preeclampsia., Patients and Methods: Altogether 100 patients with preeclampsia admitted to the Children & Women's Healthcare of Laiwu City were selected. They were divided into control group and experimental group according to different treatment methods. Among them, 51 patients in the control group were treated with magnesium sulfate combined with nifedipine, and 49 patients in the experimental group were treated with labetalol on the basis of the treatment in the control group. The therapeutic effects of the two methods were compared. The levels of the following factors in the two groups were compared: kallikrein expression, pregnancy-associated plasma protein A (PAPP-A), pregnancy-specific β1 glycoprotein (SPI), placental growth factor (PLGF), human placental prolactin (HPL), transforming growth factor β1(TGF-β1), vascular cell adhesion molecule 1 (VCAM-1) and E-selectin in serum and placenta tissues., Results: After treatment, the blood pressure in the experimental group was lower than that in the control group (p<0.05). The expression of kallikrein in serum and placental tissue of the patients in the experimental group was higher than that of the patients in the control group (p<0.05); PAPP-A level was lower than that in the control group (p<0.05); TGF-β1 level was higher than that in the control group (p<0.05); VCAM-1 and E-selectin were lower than those in the control group (p<0.05), and kallikrein and TGF-β1 in serum and placenta in the non-occurrence group were higher than those in the occurrence group (p<0.05). The serum and placenta PAPP-A, VCAM-1, and E-selectin in the non-occurrence group were lower than those in the occurrence group (p<0.05)., Conclusions: Magnesium sulfate combined with nifedipine and labetalol has good efficacy in the treatment of preeclampsia. They can promote the expression of endogenous kallikrein, reduce the level of pregnancy-related hypertension predictors, and weaken the infiltration ability of cytotrophoblasts.

Background: Deliberate hypotension is used to provide a bloodless field during functional endoscopic sinus surgery; however, the impact of controlled hypotension during anesthesia on peripheral tissue perfusion has not been extensively evaluated. The aim of this study was to compare the impact of nitroglycerin- versus labetalol-induced hypotension on peripheral perfusion., Methods: The present randomized, double-blinded, controlled trial included adult patients undergoing endoscopic sinus surgery. Patients were allocated to one of two groups according to the drug received for induction of deliberate hypotension: nitroglycerin (n = 20) or labetalol (n = 20). Mean arterial pressure was maintained at 55-65 mmHg in both groups. Both study groups were compared according to pulse oximeter-derived peripheral perfusion index (primary outcome), serum lactate level, mean arterial pressure, heart rate, surgical field score, and intraoperative blood loss., Results: Forty patients were included in the final analysis. The nitroglycerin group exhibited a higher peripheral perfusion index at nearly all records (p < 0.0001) and lower postoperative serum lactate levels (1.3 ± 0.2 mmol/L vs. 1.7 ± 0.4 mmol/L; p = 0.001) than the labetalol group. The peripheral perfusion index was higher in the nitroglycerin group than at baseline at most intraoperative readings. The median surgical field score was modestly lower in the labetalol group than in the nitroglycerin group in the first 20 min (2 [interquartile range (IQR) 2-2.5] versus 1.5 [IQR 1-2]; p = 0.001). Both groups demonstrated comparable and acceptable surgical field scores in all subsequent readings., Conclusion: Nitroglycerin-induced deliberate hypotension was accompanied by higher peripheral perfusion index and lower serum lactate levels than labetalol-induced deliberate hypotension during sinus endoscopic surgery., Trial Registration: The study was registered at clinicaltrials registry system with trial number: NCT03809065. Registered at 19 January 2019. This study adheres to CONSORT guidelines.

Background and Purpose: A subset of ischemic stroke patients present with blood pressures above that considered safe for thrombolytic administration, requiring antihypertensive therapy. Guideline statements are ambivalent regarding which antihypertensive agent should be used to obtain a satisfactory blood pressure < 185/110 mm Hg prior to alteplase., Methods: We reviewed data from consecutive patients at a single institution treated with alteplase from January 2014 to January 2019, collecting door-to-needle times, antihypertensive agent (if used), and antihypertensive-to-needle times. Patients were grouped by initial agent administered. We assessed for differences in door-to-needle times between those needing antihypertensive(s) and those who did not. Antihypertensive-to-needle times were compared across 3 antihypertensive groups (labetalol, nicardipine, and hydralazine)., Results: Analysis included 239 patients: 177 receiving no antihypertensive, 44 labetalol, 13 nicardipine, and 5 hydralazine. Those not administered an antihypertensive prior to alteplase had shorter door-to-needle times (52.6 minutes versus 62.1 minutes, P = .016). We found no statistical differences when comparing door-to-needle times across all groups (no med 52.6 minutes, labetalol 64.3 minutes, nicardipine 53.0 minutes, hydralazine 67.4 minutes, P = .052). No differences were found in antihypertensive-to-needle amongst the 3 antihypertensive groups (labetalol 18.75 minutes, nicardipine 12.15 minutes, hydralazine 25.40 minutes, P = .239)., Conclusions: Patients requiring antihypertensives experienced slower door-to-needle times. No statistically significant changes were observed in door-to-needle times by antihypertensive used, however these results may have clinical importance. This study is limited by relatively small sample size. Pooling data from multiple institutions could provide more robust assessment and inform clinical practice., (Copyright © 2019 Elsevier Inc. All rights reserved.)

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.)

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)., (Copyright © 2019 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Introduction: This study was conducted to compare the effect of dexmedetomidine and labetalol on hemodynamic variables in patients undergoing microlaryngoscopy., Material and Methods: In this randomized clinical trial study 70 patients undergoing microlaryngoscopy were involved. The patients were randomly assigned into two groups. Patients in dexmedetomidine group received 0.5 μg/kg of dexmedetomidine diluted in 100 ml of saline solution and the patients in the second group received 0.25 mg/kg of labetalol before anesthesia induction. At the beginning of the surgery, dexmedetomidine was infused at the dose of 0.4 μg/kg/h in the dexmedetomidine group, and labetalol at the dose of 1.8 mg/kg/h in the labetalol group. Patients' systolic blood pressure, diastolic blood pressure, mean arterial blood pressure and heart rate at different times and anesthesia and surgery duration, recovery time and dose of prescribed propofol were recorded and compared between two groups., Results: There was a significant difference in mean systolic blood pressure, mean diastolic blood pressure, mean arterial blood pressure and mean heart rate between two groups at different times (p value < 0.05)., Conclusion: The results of this study indicated that dexmedetomidine had higher efficacy, compared to labetalol, in reducing diastolic blood pressure, systolic blood pressure, heart rate, and mean arterial blood pressure following microlaryngoscopy.

Estimates of adherence to antihypertensive treatment in pregnancy are limited; identifying non-adherence could facilitate intervention and optimise blood pressure control. This study aimed to evaluate adherence to antihypertensive treatment amongst pregnant women with chronic hypertension using high-performance liquid chromatography-tandem mass spectrometry instrumentation. Spot urine samples collected from women who were randomised to labetalol or nifedipine were assessed. Samples from 74 women were included; documented prescribing and urine metabolite detection were concordant in 88% (n = 65). Evidence of self-administration of alternative treatment was observed in 8% (n = 6). Measurement of urinary antihypertensive metabolites in pregnancy provides insight into treatment adherence., (Copyright © 2019 International Society for the Study of Hypertension in Pregnancy. Published by Elsevier B.V. All rights reserved.)

Objective: To compare the efficacy of intravenous labetalol with oral nifedipine in the treatment of severe hypertension in pregnancy with blood pressure ≥160/110 mm Hg., Design, Setting and Participants: We conducted a parallel double-blinded randomized controlled trial between December 2014 to December 2016 in 120 antenatal women of gestational age >28 weeks, admitted with severe hypertension of blood pressure ≥160/110 mm Hg to maternity ward at a tertiary hospital. The labetalol group received 20 mg initially followed by escalating doses of 40 mg, 80 mg, 80 mg and 80 mg (5 doses) every 15 min to a maximum of 300 mg. Nifedipine group received 10 mg initially followed by repeated doses of 20 mg every 15 min (total 5 doses) to a maximum of 90 mg. Vital signs were recorded every 15 min. -The time taken and the number of doses required to achieve the target blood pressure (150/100 mmHg). Survival analysis was used to compare the efficacy of treatment regimens., Results: Sixty women were randomised to each group and none were lost to follow-up. None of the patients in nifedipine group required labetalol, whereas three patients in labetalol group achieved target BP only after receiving nifedipine was administered after the maximum dose of labetalol.The mean time taken to achieve the target blood pressure in the labetalol group was higher (36.75 min) than in the nifedipine group (27.25 min) [mean difference 9.5 min,p = 0.002]. Nifedipine group required significantly lower doses (1.82 ± 0.83) as compared to labetalol (2.45 ± 1.32) [p = 0.002]. Nifedipine was 1.8 times more likely to achieve target blood pressure (Hazard Ratio = 1.8)., Conclusions: Both intravenous Labetalol and oral Nifedipine were effective in controlling blood pressure. Nifedipine reduced BP more rapidly than Labetalol. Oral Nifedipine may be a better alternative because of its ease of oral administration and a flat dosing regimen., (Copyright © 2019 Elsevier B.V. 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 elevated blood pressure (BP) is common in the hospital. There is no evidence supporting the use of intravenous (IV) antihypertensives in this setting., Objective: To determine the prevalence and effects of treating asymptomatic elevated BP with IV antihypertensives and to investigate the efficacy of a quality improvement (QI) initiative aimed at reducing utilization of these medications., Design: Retrospective cohort study., Setting: Urban academic hospital., Patients: Patients admitted to the general medicine service, including the intensive care unit (ICU), with ≥1 episode of asymptomatic elevated BP (>160/90 mm Hg) during hospitalization., Intervention: A two-tiered, QI initiative., Measurements: The primary outcome was the monthly proportion of patients with asymptomatic elevated BP treated with IV labetalol or hydralazine. We also analyzed median BP and rates of balancing outcomes (ICU transfers, rapid responses, cardiopulmonary arrests)., Results: We identified 2,306 patients with ≥1 episode of asymptomatic elevated BP during the 10-month preintervention period, of which 251 (11%) received IV antihypertensives. In the four-month postintervention period, 70 of 934 (7%) were treated. The odds of being treated were 38% lower in the postintervention period after adjustment for baseline characteristics, including length of stay and illness severity (OR = 0.62; 95% CI 0.47-0.83; P = .001). Median SBP was similar between pre- and postintervention (167 vs 168 mm Hg; P = .78), as were the adjusted proportions of balancing outcomes., Conclusions: Hospitalized patients with asymptomatic elevated BP are commonly treated with IV antihypertensives, despite the lack of evidence. A QI initiative was successful at reducing utilization of these medications.

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.

Objective: To compare the efficacy of intravenous labetalol or oral nifedipine in treatment of acute maternal hypertension and study the fetal hemodynamic changes using color Doppler ultrasound that follows treatment., Study Design: Thirty women with severe preeclampsia having acute hypertension (more than or equal to 160/105 mmHg) were randomized in 2 groups to receive intravenous labetalol or oral nifedipine until blood pressure was lowered to less than or equal to 140/90 mmHg. Doppler vascular indices namely pulsatility index, resistance index, S/D ratio of umbilical (UA) and middle cerebral artery (MCA) were measured baseline at the time of acute severe hypertension and repeated after control of blood pressure, to assess the changes in fetal hemodynamics if any with labetalol or nifedipine., Results: Both nifedipine and labetalol were found to be effective when used for rapid control of blood pressure. Mean age of women in both groups and mean gestational age was statistically comparable. No change in fetal heart rate before and after treatment was observed in both groups. Doppler vascular indices of UA and MCA showed no significant changes as compared to baseline values in both groups., Conclusion: The use of labetalol and nifedipine were not related to any significant changes in fetal Doppler, which is reassuring about the safety of these drugs when treating acute severe hypertension in pregnancy. Choice between these two drugs should be based on cost, availability respective contraindications, and clinician's experience., (Copyright © 2018. Published by Elsevier B.V.)

Background and Rationale: Uncertainty persists over the optimal management of blood pressure (BP) in the early phase of acute ischemic stroke (AIS). This study aims to determine the safety and effects of intensive BP lowering on cerebral blood flow (CBF) and functional in AIS patients treated with intravenous thrombolysis., Methods: In a randomized controlled trial, 54 thrombolysed AIS patients with a systolic BP of 160 to 180 mm Hg will be randomized to early intensive BP lowering (systolic target range 140-160 mm Hg) or guideline-based BP management (systolic range 160-180 mm Hg) during first 72-hours using primarily intravenous labetalol. We hypothesize that early intensive BP lowering will not reduce CBF by 20% and/or increase the volume of hypoperfused tissue by >20% on computed tomographic perfusion. Clinical outcome will be assessed using a dichotomized modified Rankin scale (scores 0-1 as excellent outcome vs scores 2-6 as dead or dependent) at 90 days. Other outcome would be symptomatic intracerebral hemorrhage. The trial is registered at ClinicalTrials.gov, NCT03443596., Conclusion: This randomized study will provide important information about the physiological effects of BP reduction on cerebral perfusion after intravenous thrombolysis in AIS.

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.)

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.)

Hypertensive disorders complicating pregnancy can be classified as gestational hypertension, mild preeclampsia, and severe preeclampsia. It is necessary to evaluate and predict the grade in advance. The first study comprised 40 healthy pregnancies, 40 gestational hypertension, 40 mild preeclampsia, and 40 severe preeclampsia cases. The participants' lipid profile and cytokine levels were statistically compared. The efficacy and safety of oral nifedipine (n = 71) and intravenous labetalol (n = 72) for the treatment of severe preeclampsia were evaluated in the next study according to maternal and neonatal outcomes. The levels of lipid profile and cytokines were linked with the presence and severity of hypertensive disorders complicating pregnancy. Both oral nifedipine and intravenous labetalol are effective for safely reducing blood pressure to target levels in patients with severe preeclampsia. Our study suggests that lipid profile and cytokines can be used in the evaluation of the severity of hypertensive disorders complicating pregnancy, and oral nifedipine requires more study., (©2018 Wiley Periodicals, Inc.)

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.

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., (© 2017 American Heart Association, Inc.)

This observational retrospective cohort study was conducted to compare oral nifedipine and labetalol for emergency treatment of hypertension in preeclamptic patients. Time (minutes) and necessary doses were outlined to achieve blood pressure lower than 150/95 mmHg. In 14 patients with preeclampsia, 55 hypertensive emergencies were identified (BP >150/95). Of these emergencies, 43 were treated with oral nifedipine 10 mg (10 patients) and 12 with oral labetalol 100 mg (4 patients). To achieve a target blood pressure under 150/95, these doses were repeated as necessary every 20 min, up to a maximum of 4 doses. Oral nifedipine reduced BP more rapidly (31.30 vs. 53.50 min, p = .03). No maternal or foetal adverse events were observed and no major differences were found according to the type of delivery. Oral nifedipine is faster than and at least as safe as labetalol in pre-eclampsia hypertensive emergency treatment.

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 assess the efficacy of labetalol versus nitroglycerin for induction of controlled hypotension during sinus endoscopic surgery., Design: A prospective, double-blind and randomized study., Setting: Carried out in operating room in university hospital., Patients: 60 patients of both sexes, American Society of Anesthesiologists (ASA) physical status I and II, age range from 20 to 60years; scheduled for elective sinus endoscopic surgery under general anesthesia (GA)., Interventions: Patients were divided into two groups (30 each). NTG group received nitroglycerin infusion at a dose of 2-5μg/kg/min, LAB group received labetalol infusion at a dose of 0.5-2mg/min., Measurements: Surgical condition was assessed by surgeon using average category scale (ACS) of 0-5, a value of 2-3 being ideal. In both groups mean arterial blood pressure (MAP) was gradually reduced till the ideal ACS for assessment of surgical condition, the target of ACS was 2-3 or lower., Results: Both studied drugs achieved desired hypotension and improved visualization of surgical field by decreasing bleeding in the surgical site, but ideal surgical conditions were created at mild hypotension (MAP 70-75) in LAB group while same conditions were created at MAP of 65-69mmHg in NTG group. Mean heart rate (HR) was significantly higher in NTG group as compared to LAB group. Blood loss decreased significantly in LAB group., Conclusion: Both labetalol and NTG are effective and safe drugs for induction of controlled hypotension during sinus endoscopic surgery. While, labetalol was better as it offered optimum operative condition with mild decrease in blood pressure, decreased surgical bleeding and less tachycardia during the surgery., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Acute-onset, severe systolic hypertension; severe diastolic hypertension; or both can occur during the prenatal, intrapartum, or postpartum periods. Pregnant women or women in the postpartum period with acute-onset, severe systolic hypertension; severe diastolic hypertension; or both require urgent antihypertensive therapy. Introducing standardized, evidence-based clinical guidelines for the management of patients with preeclampsia and eclampsia has been demonstrated to reduce the incidence of adverse maternal outcomes. Individuals and institutions should have mechanisms in place to initiate the prompt administration of medication when a patient presents with a hypertensive emergency. Treatment with first-line agents should be expeditious and occur as soon as possible within 30-60 minutes of confirmed severe hypertension to reduce the risk of maternal stroke. Intravenous labetalol and hydralazine have long been considered first-line medications for the management of acute-onset, severe hypertension in pregnant women and women in the postpartum period. Although relatively less information currently exists for the use of calcium channel blockers for this clinical indication, the available evidence suggests that immediate release oral nifedipine also may be considered as a first-line therapy, particularly when intravenous access is not available. In the rare circumstance that intravenous bolus labetalol, hydralazine, or immediate release oral nifedipine fails to relieve acute-onset, severe hypertension and is given in successive appropriate doses, emergent consultation with an anesthesiologist, maternal-fetal medicine subspecialist, or critical care subspecialist to discuss second-line intervention is recommended.

Acute-onset, severe systolic hypertension; severe diastolic hypertension; or both can occur during the prenatal, intrapartum, or postpartum periods. Pregnant women or women in the postpartum period with acute-onset, severe systolic hypertension; severe diastolic hypertension; or both require urgent antihypertensive therapy. Introducing standardized, evidence-based clinical guidelines for the management of patients with preeclampsia and eclampsia has been demonstrated to reduce the incidence of adverse maternal outcomes. Individuals and institutions should have mechanisms in place to initiate the prompt administration of medication when a patient presents with a hypertensive emergency. Treatment with first-line agents should be expeditious and occur as soon as possible within 30-60 minutes of confirmed severe hypertension to reduce the risk of maternal stroke. Intravenous labetalol and hydralazine have long been considered first-line medications for the management of acute-onset, severe hypertension in pregnant women and women in the postpartum period. Although relatively less information currently exists for the use of calcium channel blockers for this clinical indication, the available evidence suggests that immediate release oral nifedipine also may be considered as a first-line therapy, particularly when intravenous access is not available. In the rare circumstance that intravenous bolus labetalol, hydralazine, or immediate release oral nifedipine fails to relieve acute-onset, severe hypertension and is given in successive appropriate doses, emergent consultation with an anesthesiologist, maternal-fetal medicine subspecialist, or critical care subspecialist to discuss second-line intervention is recommended.

What Is Known and Objective: Pre-eclampsia is one of the most challenging diseases of pregnancy. Both nifedipine and labetalol have been used for treatment of pregnancy-induced severe pre-eclampsia., Methods: In the present study, the efficacy and safety of oral nifedipine and intravenous labetalol for severe pre-eclampsia therapy were compared. Eligible pregnant women with severe pre-eclampsia (n = 147) were allocated to receive either oral nifedipine or intravenous labetalol. The primary endpoint of the study was the time needed to achieve target blood pressure. Secondary outcomes were the time interval before a new hypertensive crisis following effective blood pressure control, number of doses and adverse effects., Results and Discussion: We found that the time taken to achieve effective blood pressure control was 35 vs. 42 min for oral nifedipine and intravenous labetalol, respectively (P = 0·37). Compared with labetalol group, no significant difference was observed regarding time interval and drug dosages in nifedipine arm. Moreover, no serious side effects on maternal or perinatal were observed in either group., What Is New and Conclusions: These findings suggest that both oral nifedipine and intravenous labetalol are effective for safely reducing blood pressure to target levels in patients with severe pre-eclampsia., (© 2016 John Wiley & Sons Ltd.)

To determine whether clinical outcomes differed by occurrence of severe hypertension in the international CHIPS trial (Control of Hypertension in Pregnancy Study), adjusting for the interventions of "less tight" (target diastolic blood pressure [dBP] 100 mm Hg) versus "tight" control (target dBP 85 mm Hg). In this post-hoc analysis of CHIPS data from 987 women with nonsevere nonproteinuric preexisting or gestational hypertension, mixed effects logistic regression was used to compare the following outcomes according to occurrence of severe hypertension, adjusting for allocated group and the influence of baseline factors: CHIPS primary (perinatal loss or high-level neonatal care for >48 hours) and secondary outcomes (serious maternal complications), birth weight <10th percentile, preeclampsia, delivery at <34 or <37 weeks, platelets <100×10 9 /L, elevated liver enzymes with symptoms, maternal length of stay ≥10 days, and maternal readmission before 6 weeks postpartum. Three hundred and thirty-four (34.1%) women in CHIPS developed severe hypertension that was associated with all outcomes examined except for maternal readmission (P=0.20): CHIPS primary outcome, birth weight <10th percentile, preeclampsia, preterm delivery, elevated liver enzymes (all P<0.001), platelets <100×10 9 /L (P=0.006), and prolonged hospital stay (P=0.03). The association between severe hypertension and serious maternal complications was seen only in less tight control (P=0.02). Adjustment for preeclampsia (464, 47.3%) did not negate the relationship between severe hypertension and the CHIPS primary outcome (P<0.001), birth weight <10th percentile (P=0.005), delivery at <37 (P<0.001) or <34 weeks (P<0.001), or elevated liver enzymes with symptoms (P=0.02). Severe hypertension is a risk marker for adverse maternal and perinatal outcomes, independent of BP control or preeclampsia co-occurrence., Clinical Trial Registration: URL: http://pre-empt.cfri.ca/. Unique identifier: ISRCTN 71416914. URL: https://www.clinicaltrials.gov/. Unique identifier: NCT01192412., (© 2016 The Authors.)

Hypertensive disorders of pregnancy affect approximately one in ten pregnancies and often persist postpartum. Their postnatal course can be unpredictable and complications may occur, hence control remains important but is informed by little evidence. Clinicians from UK primary and secondary healthcare were invited to complete a survey regarding antihypertensive adjustment postpartum. The response rate was 101/390 (26%). Labetalol was the commonest antihypertensive used. Most participants reported following national guidelines when reducing, although not increasing, antihypertensive medications. The results suggest an unwarranted and unjustifiable variation in management - underlining the evidence gap - additional research is needed to inform the standardisation of care., (Copyright © 2016 International Society for the Study of Hypertension in Pregnancy. Published by Elsevier B.V. All rights reserved.)

Background and Objectives: β blockers are widely used in the treatment of hypertensive disorders during pregnancy. These medications cross the placenta and may cause physiologic changes in neonates exposed in utero. We sought to define the risks of neonatal hypoglycemia and bradycardia associated with maternal exposure to β blockers at the time of delivery in a large, nationwide cohort of Medicaid beneficiaries., Methods: We used a cohort of 2 292 116 completed pregnancies linked to liveborn infants of Medicaid-enrolled women from 2003 to 2007. We examined the risks of neonatal hypoglycemia and neonatal bradycardia associated with maternal exposure to β blockers at the time of delivery. Propensity score matching was used to control for potential confounders including maternal demographics, obstetric and medical conditions, and exposure to other medications., Results: There were 10 585 (0.5%) pregnancies exposed to β blockers at the time of delivery. The risk of neonatal hypoglycemia was 4.3% in the β blocker-exposed neonates versus 1.2% in the unexposed; the risk of neonatal bradycardia was 1.6% in the exposed versus 0.5% in the unexposed. After controlling for confounders, risk remained elevated for both neonatal hypoglycemia and bradycardia among exposed pregnancies versus unexposed (adjusted odds ratio, 1.68, 95% confidence interval, 1.50-1.89 and adjusted odds ratio, 1.29, 95% confidence interval, 1.07-1.55, respectively)., Conclusion: Our findings suggest that neonates born to mothers exposed to β blockers in late pregnancy, including labetalol, are at elevated risk for neonatal hypoglycemia and bradycardia., Competing Interests: POTENTIAL CONFLICT OF INTEREST: Dr Hernandez-Diaz has consulted for AstraZeneca and UCB for unrelated projects, and served as investigator on grants to the Brigham & Women’s Hospital from Lilly and Pfizer. The Pharmacoepidemiology Program at the Harvard School of Public Health is supported by Pfizer, Takeda, Bayer, and Asisa. Drs Huybrechts and Bateman are investigators on grants to the Brigham & Women’s Hospital from Lilly and Pfizer, and Dr Bateman is an investigator on grants from Baxalta, unrelated to the topic of this manuscript. The other authors have indicated they have no potential conflicts of interest to disclose., (Copyright © 2016 by the American Academy of Pediatrics.)