Pharmacological strategies to prevent haemodynamic changes after intubation in parturient women with hypertensive disorders of pregnancy: A network meta-analysis.

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; I2=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.

Blood Pressure Control in Acute Stroke: Labetalol or Nicardipine?

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.

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

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

Intravenous labetalol versus oral nifedipine for acute hypertension in pregnancy: effects on cerebral perfusion pressure.

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.

Retrospective evaluation of labetalol as antihypertensive agent in dogs.

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.

Effects of nitroglycerin versus labetalol on peripheral perfusion during deliberate hypotension for sinus endoscopic surgery: a randomized, controlled, double-blinded trial.

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.

The effects of moderate alterations in adrenergic activity on acute appetite regulation in obese women: A randomised crossover trial.

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/ß 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/m2, waist 104.8 (4.1) cm) participated in two separate, double-blind randomised experimental trials. Experiment 1: moderate exercise after α/ß 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/ß adrenergic blockade nor moderate increases in adrenergic activity induced by intravenous adrenaline infusion affected acute appetite regulation.

Delay to Tissue Plasminogen Activator in Hypertensive Stroke Patients: An Analysis of Delay Duration Across Agents.

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.

Neonatal hypertension: cases, causes, and clinical approach.

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.

Comparing the effect of dexmedetomidine and labetalol on hemodynamic variables in patients undergoing microlaryngoscopy.

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.

Drugs for treating severe hypertension in pregnancy: a network meta-analysis and trial sequential analysis of randomized clinical trials.

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.

Continuous-Infusion Labetalol vs Nicardipine for Hypertension Management in Stroke Patients.

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.

A trial of oral nifedipine and oral labetalol in preeclampsia hypertensive emergency treatment.

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.

Response & Side Effects of Injectable Labetalol in Pregnancy Induced Severe Hypertension.

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.

The sympathetic nervous system is controlled by transient receptor potential vanilloid 1 in the regulation of body temperature.

Transient receptor potential vanilloid 1 (TRPV1) is involved in sensory nerve nociceptive signaling. Recently, it has been discovered that TRPV1 receptors also regulate basal body temperature in multiple species from mice to humans. In the present study, we investigated whether TRPV1 modulates basal sympathetic nervous system (SNS) activity. C57BL6/J wild-type (WT) mice and TRPV1 knockout (KO) mice were implanted with radiotelemetry probes for measurement of core body temperature. AMG9810 (50 mg/kg) or vehicle (2% DMSO/5% Tween 80/10 ml/kg saline) was injected intraperitoneally. Adrenoceptor antagonists or vehicle (5 ml/kg saline) was injected subcutaneously. In WT mice, the TRPV1 antagonist, AMG9810, caused significant hyperthermia, associated with increased noradrenaline concentrations in brown adipose tissue. The hyperthermia was significantly attenuated by the ß-adrenoceptor antagonist propranolol, the mixed α-/ß-adrenoceptor antagonist labetalol, and the α1-adrenoceptor antagonist prazosin. TRPV1 KO mice have a normal basal body temperature, indicative of developmental compensation. d-Amphetamine (potent sympathomimetic) caused hyperthermia in WT mice, which was reduced in TRPV1 KO mice, suggesting a decreased sympathetic drive in KOs. This study provides new evidence that TRPV1 controls thermoregulation upstream of the SNS, providing a potential therapeutic target for sympathetic hyperactivity thermoregulatory disorders.

Severe maternal morbidity in a large cohort of women with acute severe intrapartum hypertension.

BACKGROUND: Hypertensive diseases of pregnancy are associated with severe maternal morbidity and remain common causes of maternal death. Recently, national guidelines have become available to aid in recognition and management of hypertension in pregnancy to reduce morbidity and mortality. The increased morbidity related to hypertensive disorders of pregnancy is presumed to be associated with the development of severe hypertension. However, there are few data on specific treatment or severe maternal morbidity in women with acute severe intrapartum hypertension as opposed to severe preeclampsia. OBJECTIVE: The study aimed to characterize maternal morbidity associated with women with acute severe intrapartum hypertension, and to determine whether there was an association between various first-line antihypertensive agents and posttreatment blood pressure. STUDY DESIGN: This retrospective cohort study of women delivering between July 2012 and August 2014 at 15 hospitals participating in the California Maternal Quality Care Collaborative compared women with severe intrapartum hypertension (systolic blood pressure >160 mm Hg or diastolic blood pressure >105 mm Hg) to women without severe hypertension. Hospital Patient Discharge Data and State of California Birth Certificate Data were used. Severe maternal morbidity using the Centers for Disease Control and Prevention criteria based on International Classification of Diseases-9 codes was compared between groups. The efficacy of different antihypertensive medications in meeting the 1-hour posttreatment goal was determined. Statistical methods included distribution appropriate univariate analyses and multivariate logistic regression. RESULTS: There were 2252 women with acute severe intrapartum hypertension and 93,650 women without severe hypertension. Severe maternal morbidity was significantly more frequent in the women with severe hypertension (8.8%) compared to the control women (2.3%) (P < .0001). Severe maternal morbidity rates did not increase with increasing severity of blood pressures (P = .90 for systolic and .42 for diastolic). There was no difference in severe maternal morbidity between women treated (8.6%) and women not treated (9.5%) (P = .56). Antihypertensive treatment rates were significantly higher in hospitals with a level IV neonatal intensive care unit (85.8%) compared to a level III neonatal intensive care unit (80.2%) (P < .001), and in higher-volume hospitals (84.5%) compared to lower-volume hospitals (69.1%) (P < .001). Severe maternal morbidity rates among severely hypertensive women were significantly higher in hospitals with level III neonatal intensive care unit level compared to hospitals with a level IV neonatal intensive care unit (10.6% vs 5.7%, respectively; P < .001), and significantly higher in low-delivery volume hospitals compared to high-delivery volume hospitals (15.5% vs 7.6%, respectively; P < .001). Only 53% of women treated with oral labetalol as first-line medication met the posttreatment goal of nonsevere hypertension, significantly less than those treated with intravenous hydralazine, intravenous labetalol, or oral nifedipine (68%, 71%, and 82%, respectively) (P = .001). Severe intrapartum hypertension remained untreated in 17% of women. CONCLUSION: Women with acute severe intrapartum hypertension had a significantly higher risk of severe maternal morbidity compared to women without severe hypertension. Significantly lower antihypertensive treatment rates and higher severe maternal morbidity rates were seen in lower-delivery volume hospitals.

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

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

Oral nifedipine vs. intravenous labetalol for treatment of pregnancy-induced severe pre-eclampsia.

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.

Oral antihypertensive therapy for severe hypertension in pregnancy and postpartum: a systematic review.

BACKGROUND: Pregnant and postpartum women with severe hypertension are at increased risk of stroke and require blood pressure (BP) reduction. Parenteral antihypertensives have been most commonly studied, but oral agents would be ideal for use in busy and resource-constrained settings. OBJECTIVES: To review systematically, the effectiveness of oral antihypertensive agents for treatment of severe pregnancy/postpartum hypertension. SEARCH STRATEGY: A systematic search of MEDLINE, EMBASE and the Cochrane Library was performed. SELECTION CRITERIA: Randomised controlled trials in pregnancy and postpartum with at least one arm consisting of a single oral antihypertensive agent to treat systolic BP ≥ 160 mmHg and/or diastolic BP ≥ 110 mmHg. DATA COLLECTION AND ANALYSIS: Cochrane RevMan 5.1 was used to calculate relative risk (RR) and weighted mean difference by random effects. MAIN RESULTS: We identified 15 randomised controlled trials (915 women) in pregnancy and one postpartum trial. Most trials in pregnancy compared oral/sublingual nifedipine capsules (8-10 mg) with another agent, usually parenteral hydralazine or labetalol. Nifedipine achieved treatment success in most women, similar to hydralazine (84% with nifedipine; relative risk [RR] 1.07, 95% confidence interval [95% CI] 0.98-1.17) or labetalol (100% with nifedipine; RR 1.02, 95% CI 0.95-1.09). Less than 2% of women treated with nifedipine experienced hypotension. There were no differences in adverse maternal or fetal outcomes. Target BP was achieved ~ 50% of the time with oral labetalol (100 mg) or methyldopa (250 mg) (47% labetelol versus 56% methyldopa; RR 0.85 95% CI 0.54-1.33). CONCLUSIONS: Oral nifedipine, and possibly labetalol and methyldopa, are suitable options for treatment of severe hypertension in pregnancy/postpartum.

Impact of initial blood pressure on antihypertensive response in patients with acute hypertension.

INTRODUCTION: The effect profile of differing antihypertensive agents is well studied, but minimal data regarding the interaction between hemodynamic response and presenting blood pressure (BP) exist. HYPOTHESIS: Achievement of target BP is less likely in patients with higher initial BPs. METHODS: This is a substudy of the multicenter safety and efficacy Evaluation of intravenous Cardene (nicardipine) and Labetalol Use in the Emergency department (CLUE) trial that randomized patients to Food and Drug Administration-recommended intravenous dosing of nicardipine or labetalol to reach a physician predefined systolic BP (SBP) and target range (TR) of ±20 mm Hg within 30 minutes. The proportion achieving TR was assessed as a function of initial SBP, and dichotomized comparisons were made using median SBP. Likelihood of a final BP within TR was modeled using logistic regression with forced inclusion of initial BP as a categorical variable. RESULTS: A total 223 patients were enrolled; 115 (51.6%) had an initial SBP greater than the median 202 mm Hg. The median SBP (interquartile range) of the high BP group was 218 (210-228) mm Hg vs the low BP group 190 (182-197) mm Hg (P < 0.0001). No groupwise differences existed except that the high group had higher mean (SD) serum creatinine level at baseline (3.1 [3.9] vs 1.9 [2.3], P = .008). The proportion of patients achieving SBP within TR at 30 minutes did not differ (85.2% [98 of 115] vs 88.9% [96 of 108], P = .42). Randomization to nicardipine (odds ratio = 2.85; 95% confidence interval, 1.16-7.01), but not initial SBP (odds ratio = 0.60; 95% confidence interval, 0.25-1.44), was associated with achievement of target SBP at 30 minutes. CONCLUSION: Initial SBP is not a predictor of the ability to achieve a prespecified target range SBP within 30 minutes.