Antihypertensive treatment during pregnancy induces long-term changes in gut microbiota and the behaviors of the attention deficit hyperactivity disorder offspring.

The pathogenesis of attention-deficit/hyperactivity disorder (ADHD) has not been fully elucidated. Gestational hypertension could double the probability of ADHD in the offspring, while the initial bacterial communication between the mother and offspring has been associated with psychiatric disorders. Thus, we hypothesize that antihypertensive treatment during pregnancy may abate the impairments in neurodevelopment of the offspring. To test this hypothesis, we chose Captopril and Labetalol, to apply to pregnant spontaneously hypertensive rat (SHR) dams and examined the outcomes in the male offspring. Our data demonstrated that maternal treatment with Captopril and Labetalol had long-lasting changes in gut microbiota and behavioral alterations, including decreased hyperactivity and increased curiosity, spatial learning and memory in the male offspring. Increased diversity and composition were identified, and some ADHD related bacteria were found to have the same change in the gut microbiota of both the dam and offspring after the treatments. LC-MS/MS and immunohistochemistry assays suggested elevated expression of brain derived neurotrophic factor (BDNF) and dopamine in the prefrontal cortex and striatum of offspring exposed to Captopril/ Labetalol, which may account for the improvement of the offspring's psychiatric functions. Therefore, our results support the beneficial long-term effects of the intervention of gestational hypertension in the prevention of ADHD.

Risk of postpartum readmission after hypertensive disorder of pregnancy and variation by discharge antihypertensive medication prescription.

BACKGROUND: Patients with hypertensive disorders of pregnancy have a high rate of postpartum readmission. OBJECTIVE: This study aimed to evaluate whether the type of antihypertensive medication prescribed at discharge was associated with postpartum readmission after a hypertensive disorder of pregnancy. STUDY DESIGN: This was a retrospective cohort study of 57,254 pregnancies complicated by hypertensive disorders of pregnancy between 2012 and 2018 in the electronic obstetrical database of Kaiser Permanente Northern California. Postpartum readmissions occurred within 6 weeks after discharge from delivery hospitalization. Cox regression models were used to evaluate the association between the type of antihypertensive medication prescription at discharge (none, labetalol only, nifedipine only, or 2 or more antihypertensive medications) and postpartum readmission, adjusted for type of hypertensive disorder of pregnancy, final inpatient systolic and diastolic blood pressures, age, body mass index, mode of delivery, insurance status, race and ethnicity, delivery facility, comorbidity score, smoking, preterm delivery, parity, and Neighborhood Deprivation Index. RESULTS: Among eligible patients with a hypertensive disorder of pregnancy, 1696 (3.0%) were readmitted within 6 weeks. Approximately 86% of patients were discharged without a prescription for antihypertensive medication; among those discharged with a prescription for antihypertensive medication, most were prescribed either labetalol only (54%) or nifedipine only (30%). The unadjusted readmission risk was the highest for patients discharged with a prescription for labetalol only (7.6%), lower for those discharged with a prescription for nifedipine only (3.6%) or 2 or more antihypertensive medications (3.2%), and the lowest for those discharged without a prescription for antihypertensive medication (2.5%). In the adjusted models, compared with discharge without a prescription for antihypertensive medication, discharge with a prescription for labetalol only was associated with a 63% (hazard ratio, 1.63; 95% confidence interval, 1.41-1.88) greater incidence of postpartum readmission, and discharge with a prescription for nifedipine only and discharge with a prescription for 2 or more antihypertensive medications were associated with 26% (hazard ratio, 0.74; 95% confidence interval, 0.59-0.93) and 47% (hazard ratio, 0.53; 95% confidence interval, 0.38-0.74) lower incidence of postpartum readmission, respectively. There was no strong evidence to suggest that the effect of the type of antihypertensive medication at discharge on the incidence of readmission varied by race and ethnicity (interaction P=.88). The results indicating an elevated risk associated with labetalol use were consistent in models that excluded patients with prepregnancy hypertension. CONCLUSION: Discharge with a prescription for nifedipine alone or multiple antihypertensive medications (vs no medication) was associated with a lower incidence of readmission, whereas discharge with a prescription for labetalol alone was associated with an elevated readmission incidence. A large-scale, prospective research to compare the effectiveness of commonly prescribed hypertension medications at discharge is warranted.

Effect of low-molecular-weight heparin calcium combined with magnesium sulfate and labetalol on coagulation, vascular endothelial function and pregnancy outcome in early-onset severe preeclampsia.

OBJECTIVE: This paper was aimed at unveiling the effect of low-molecular-weight heparin calcium (LMWH) combined with magnesium sulfate and labetalol on coagulation, vascular endothelial function, and pregnancy outcome in early-onset severe preeclampsia (EOSP). METHODS: Pregnant women with EOSP were divided into the control group and the study group, each with 62 cases. Patients in the control group were treated with labetalol and magnesium sulfate, and those in the study group were treated with LMWH in combination with the control grou Blood pressure (systolic blood pressure [SBP] and diastolic blood pressure [DBP]), 24-h urine protein, coagulation indices [D-dimer (D-D), plasma fibrinogen (Fg), prothrombin time (PT), activated partial thromboplastin time (APTT), and prothrombin time (TT)], endothelial function [endothelin (ET-1) and nitric oxide (NO)], oxidative stress indices [oxidized low-density lipoproteins (ox-LDL), lipid peroxidation (LPO), superoxide dismutase (SOD), and malondialdehyde (MDA)], pregnancy outcome, and adverse effects occurred in the two groups were compared. RESULTS: After treatment, lower SBP, DBP, and 24-h urine protein levels; lower Fg and D-D levels; higher PT, APPT, and TT levels; higher NO levels; lower ET-1 levels; lower ox-LDL, MDA, and LPO levels; higher SOD levels; and lower incidence of adverse pregnancy and adverse reactions were noted in the study group in contrast to the control group. CONCLUSION: EOSP patients given with LMWH combined with magnesium sulfate and labetalol can effectively reduce the patient's blood pressure and urinary protein level; improve coagulation function, oxidative stress, and vascular endothelial function indices; reduce the adverse pregnancy outcomes; and improve the safety of treatment.

Lipid Emulsions Inhibit Labetalol-Induced Vasodilation in the Isolated Rat Aorta.

Lipid emulsions are used as adjuvant drugs to alleviate intractable cardiovascular collapse induced by drug toxicity. We aimed to examine the effect of lipid emulsions on labetalol-induced vasodilation and the underlying mechanism in the isolated rat aorta. We studied the effects of endothelial denudation, NW-nitro-l-arginine methyl ester (l-NAME), calmidazolium, methylene blue, 1H-[1,2,4]oxadiazolo[4,3-a] quinoxalin-1-one (ODQ), and lipid emulsions on labetalol-induced vasodilation. We also evaluated the effects of lipid emulsions on cyclic guanosine monophosphate (cGMP) formation, endothelial nitric oxide synthase (eNOS) phosphorylation, and endothelial calcium levels induced by labetalol. Labetalol-induced vasodilation was higher in endothelium-intact aortas than that in endothelium-denuded aortas. l-NAME, calmidazolium, methylene blue, and ODQ inhibited labetalol-induced vasodilation in endothelium-intact aortas. Lipid emulsions inhibited labetalol-induced vasodilation in endothelium-intact and endothelium-denuded aortas. l-NAME, ODQ, and lipid emulsions inhibited labetalol-induced cGMP formation in endothelium-intact aortas. Lipid emulsions reversed the stimulatory and inhibitory eNOS (Ser1177 and Thr495) phosphorylation induced by labetalol in human umbilical vein endothelial cells and inhibited the labetalol-induced endothelial calcium increase. Moreover, it decreased labetalol concentration. These results suggest that lipid emulsions inhibit vasodilation induced by toxic doses of labetalol, which is mediated by the inhibition of endothelial nitric oxide release and reduction of labetalol concentration.

Haemodynamic effects of labetalol in isoflurane-anaesthetized dogs that received dexmedetomidine: A randomized clinical trial.

OBJECTIVE: To test whether labetalol improved cardiovascular function in anaesthetized dogs injected with dexmedetomidine. STUDY DESIGN: Prospective, randomized, blinded, clinical trial. ANIMALS: A group of 20 healthy client-owned dogs undergoing ovariohysterectomy. METHODS: Each dog received dexmedetomidine (5 µg kg-1) and methadone (0.2 mg kg-1) intramuscularly. General anaesthesia was induced with propofol and maintained with isoflurane in oxygen. All dogs were mechanically ventilated, and epidural anaesthesia with lidocaine was performed. Standard anaesthetic monitoring, invasive blood pressure, oesophageal Doppler and near-infrared tissue perfusion/oxygenation were applied. Peak velocity (PV), mean acceleration and stroke distance (SD) from the oesophageal Doppler were recorded. Arterial elastance (Ea) was calculated. Tissue oxygenation (rStO2) was also recorded. Prior to surgery, animals received either 0.1 mg kg-1 of labetalol intravenously (IV) over 60 seconds or the equivalent volume of saline. Data were recorded for 20 minutes. Age, weight and propofol dose were compared with a Wilcoxon rank-sum test. The effects of time, treatment and their interaction with haemodynamic and perfusion variables were analysed with mixed-effect models and Tukey's post hoc tests. RESULTS: Significant effects of the interaction between treatment and time were observed whereby heart rate (HR) was higher in dogs given labetalol (p = 0.01), whereas arterial blood pressure and Ea were lower (p < 0.01). Similarly, PV, SD and rStO2 were higher in the labetalol group, and significant effects were detected for the interaction between treatment and time (p < 0.01). CONCLUSIONS AND CLINICAL RELEVANCE: Labetalol at a dose of 0.1 mg kg-1 IV in dogs under general anaesthesia and administered a pre-anaesthetic medication of dexmedetomidine produced mild vasodilation (reduction of Ea), resulting in an increase in HR and left ventricular outflow. Although labetalol could be an effective option to achieve haemodynamic optimization after dexmedetomidine-induced vasoconstriction, future studies are needed to assess long-term effects.

Physiologically Based Pharmacokinetic Modeling for Multiple Oral Administration Labetalol in Pregnant Women.

BACKGROUND: Labetalol has an irreplaceable role in treating Hypertensive disorders of pregnancy (HDP), a common disease during pregnancy with a prevalence of 5.2-8.2%. However, there were big differences in dosage regimens between various guidelines. PURPOSE: A physiologically-based pharmacokinetics (PBPK) model was established and validated to evaluate the existing oral dosage regimens, and to compare the difference in plasma concentration between pregnant and non-pregnant women. METHODS: First, non-pregnant woman models with specific plasma clearance or enzymatic metabolism (UGT1A1, UGT2B7, CYP2C19) were established and validated. For CYP2C19, slow, intermediate, and rapid metabolic phenotypes were considered. Then, a pregnant model with proper structure and parameters adjustment was established and validated against the multiple oral administration data. RESULTS: The predicted labetalol exposure captured the experimental data well. The following simulations with criteria lowering 15 mmHg blood pressure (corresponding to around 108 ng/ml plasma labetalol) found that the maximum daily dosage in the Chinese guideline may be insufficient for some severe HDP patients. Moreover, similar predicted steady-state trough plasma concentration was found between the maximum daily dosage in the American College of Obstetricians and Gynecologists (ACOG) guideline, 800 mg Q8h and a regimen of 200 mg Q6h. Simulations comparing non-pregnant and pregnant women found that the difference in labetalol exposure highly depended on the CYP2C19 metabolic phenotype. CONCLUSIONS: In summary, this work initially established a PBPK model for multiple oral administration of labetalol for pregnant women. This PBPK model may lead to personalized labetalol medication in the future.

Beta-Blockers in Pregnancy: Clinical Update.

PURPOSE OF REVIEW: The aim of this review was to determine the anticipated benefits and adverse effects of beta-blockers in pregnant women with hypertension. The other issue was to assess the possible adverse effects of beta-blockers for their babies and provide current consensus recommendations for appropriate selection and individualized antihypertensive treatment with beta-blockers in pregnancy-associated hypertension. RECENT FINDINGS: Hypertensive disorders of pregnancy are a major cause of maternal and fetal morbidity, with consequences later in life. Certain beta-blockers are useful for ameliorating hypertension in pregnancy and may have a protective role in endothelial dysfunction. However, some aspects of beta-blocker use in pregnancy are contentious among providers. Evidence on their safety, although well documented, is variable, and recent research reveals areas of controversy. Besides intrauterine growth restriction, other neonatal and obstetric complications remain a concern and should be explored thoroughly. Attention is necessary when treating pregnancy-associated hypertensive disorders with beta-blockers. Specific beta-blockers are considered safe in pregnancy, although the associated effects in the fetus are not clearly known and evidence is lacking for many safety outcomes, other than intrauterine growth restriction. Nevertheless, beta-blockers with specific indications in pregnancy under individualized selection and monitoring may confer substantial improvements in pregnant women with hypertension.

Evaluation of intravenous infusion of labetalol versus magnesium sulfate on cerebral hemodynamics of preeclampsia patients with severe features using transcranial doppler.

PURPOSE: It is essential to understand the underlying pathophysiological mechanisms of preeclampsia cerebral complications. This study aimed to compare the cerebral hemodynamic effects of magnesium sulfate (MgSO4) and labetalol in pre-eclampsia patients with severe features. METHODS: Singleton pregnant women who suffered from late onset preeclampsia with severe features were enrolled and subjected to baseline Transcranial doppler (TCD) evaluation and then randomly assigned to either the magnesium sulfate group or labetalol group. TCD to measure middle cerebral artery (MCA) blood flow indices including mean flow velocity (cm/s), mean end-diastolic velocity (DIAS), and pulsatility index (PI) and to estimate CPP and MCA velocity were performed as basal measurements before study drug administration and at post-treatment one and six hours after administration. The occurrence of seizures and any adverse effects were recorded for each group. RESULTS: Sixty preeclampsia patients with severe features were included and randomly allocated into two equal groups. In group M the PI was 0.77 ± 0.04 at baseline versus 0.66 ± 0.05 at 1hour and 0.66 ± 0.05 at 6 hours after MgSO4 administration (p value < 0.001) also the calculated CPP was significantly decreased from 103.3 ± 12.7mmHg to 87.8 ± 10.6mmHg and 89.8 ± 10.9mmHg (p value < 0.001) at 1 and 6 hours respectively. Similarly, in group L the PI was significantly decreased from 0.77 ± 0.05 at baseline to 0.67 ± 0.05 and 0.67 ± 0.06 at 1 and 6 hours (p value < 0.001) after labetalol administration. Moreover, the calculated CPP was significantly decreased from 103.6 ± 12.6 mmHg to 86.2 ± 13.02mmHg at 1 hour and to 83.7 ± 14.6mmHg at 6 hours (p value < 0.001). In terms of changes in blood pressure and the heart rate, they were significantly lower in the labetalol group. CONCLUSION: Both magnesium sulfate and labetalol reduce CPP while maintaining cerebral blood flow (CBF) in preeclampsia patients with severe features. TRIAL REGISTRATION: The institutional review board of the Faculty of Medicine, Zagazig University approved this study with the reference number (ZU-IRB#: 6353-23-3-2020) and it was registered at clinicaltrials.gov (NCT04539379).

Impact of implementation of the Maternal-Fetal Triage Index on patients presenting with severe hypertension.

BACKGROUND: Severe hypertension remains one of the leading preventable causes of maternal mortality in the United States. Timeliness to response to severe hypertension in pregnancy is a crucial quality indicator tracked by state and national organizations. We hypothesized that the implementation of the Maternal-Fetal Triage Index, a validated acuity tool, would improve care performance in women with severe hypertension in an urban, inner-city hospital setting. OBJECTIVE: This study aimed to assess the impact of the Maternal-Fetal Triage Index on the management of women presenting with severe preeclampsia diagnosed by severe hypertension as measured by time to provider assessment, administration of magnesium sulfate, and immediate administration of acute antihypertensives. STUDY DESIGN: This was a prospective, observational study of pregnant women presenting to the labor and delivery triage unit with severe preeclampsia diagnosed by severe hypertension giving birth at a large urban inner-city academic facility before (epoch 1: January 1, 2019, to December 31, 2019) and after (epoch 2: March 1, 2021, to September 31, 2021) the implementation of the Maternal-Fetal Triage Index. Baseline outcomes of time to assessment, time to magnesium sulfate prophylaxis, and time to antihypertensive medication administration before the implementation of the Maternal-Fetal Triage Index were assessed. The Maternal-Fetal Triage Index tool was implemented on March 1, 2021, following standardized education in 2020 for all triage nurses, unit technicians, healthcare unit coordinators, and healthcare providers. Time to assessment, administration of magnesium sulfate prophylaxis, and time to antihypertensive administration after the implementation of the Maternal-Fetal Triage Index were compared with measures before the implementation of the Maternal-Fetal Triage Index. Statistical analysis included Wilcoxon rank-sum test with P<.05 considered significant when comparing epoch 1 with epoch 2. RESULTS: A total of 370 patients were admitted with severe hypertension in 2019 before the use of the Maternal-Fetal Triage Index, and 254 patients were admitted with severe hypertension in 2021 after the implementation of the Maternal-Fetal Triage Index. There was no difference between epochs across baseline characteristics, including age, race and ethnicity, parity, and body mass index. After the Maternal-Fetal Triage Index was implemented, the time to provider assessment was significantly improved, from a median time of 44 minutes (interquartile range, 0-65) in epoch 1 to 17 minutes (interquartile range, 0-39) in epoch 2 (P<.001). Furthermore, the time from arrival to magnesium sulfate prophylaxis was significantly faster with a median time of 161 minutes (interquartile range, 109-256) in epoch 1 vs 127 minutes (interquartile range, 85-258) in epoch 2 (P=.001). Moreover, there was a decrease in the time from arrival to antihypertensive medication administration for severe blood pressures after the implementation of the Maternal-Fetal Triage Index (101 minutes [interquartile range, 61-177] vs 66 minutes [interquartile range, 35-203]; P<.001). CONCLUSION: The implementation of the Maternal-Fetal Triage Index at a large urban inner-city hospital was associated with improved timeliness of assessment and treatment of women with severe hypertension. The Maternal-Fetal Triage Index is a viable tool to improve the efficiency in triage units, specifically in the management of severe hypertension.

Society for Maternal-Fetal Medicine Special Statement: A quality metric for evaluating timely treatment of severe hypertension.

Severe hypertension in pregnancy is a medical emergency. Although expeditious treatment within 30 to 60 minutes is recommended to reduce the risk of maternal death or severe morbidity, treatment is often delayed by >1 hour. In this statement, we propose a quality metric that facilities can use to track their rates of timely treatment of severe hypertension. We encourage facilities to adopt this metric so that future reports from different facilities will be based on a uniform definition of timely treatment.

Pharmacokinetics of the most commonly used antihypertensive drugs throughout pregnancy methyldopa, labetalol, and nifedipine: a systematic review.

PURPOSE: Antihypertensive drugs are among the most prescribed drugs during pregnancy. Methyldopa, labetalol, and nifedipine have been perceived safe to use during pregnancy and are therefore recommended in international guidelines for treatment of hypertension. In this review, we provide a complete overview of what is known on the pharmacokinetics (PK) of the antihypertensive drugs methyldopa, labetalol, and nifedipine throughout pregnancy. METHODS: A systematic search was performed to retrieve studies on the PK of methyldopa, labetalol, and nifedipine used throughout pregnancy. The search was restricted to English and original studies. The systematic search was conducted on July 27, 2021, in Embase, Medline Ovid, Web of Science, Cochrane Library, and Google Scholar. Keywords were methyldopa, labetalol, nifedipine, pharmacokinetics, pregnancy, and placenta. RESULTS: A total of 1459 unique references were identified of which title and abstract were screened. Based on this screening, 67 full-text papers were assessed, to retain 30 PK studies of which 2 described methyldopa, 12 labetalol, and 16 nifedipine. No fetal accumulation is found for any of the antihypertensive drugs studied. CONCLUSION: We conclude that despite decades of prescribing methyldopa, labetalol, and nifedipine throughout pregnancy, descriptions of their PK during pregnancy are hampered by a large heterogeneity in the low number of available studies. Aiming for evidence-based and personalized dosing of antihypertensive medication in the future, further studies on the relationship of both PK and pharmacodynamics (including the optimal blood pressure targeting) during pregnancy and pregnancy-related pathology are urgently needed to prevent undertreatment, overtreatment, and side effects.

A successful experience using labetalol and hemodialysis to treat near-fatal caffeine poisoning: A case report with toxicodynamics.

Caffeine poisoning is relatively rare, and a near-fatal caffeine overdose is highly uncommon. We present an 18-year-old male who attempted suicide with 295 mg/kg pure caffeine powder (lethal oral dose: 150-200 mg/kg) and was successfully rescued. He presented with seizures, refractory supraventricular tachycardia and hypertension for 6 h with no response to medications and cardioversion. Even with the high level of caffeine, labetalol, which is seldom administered as a treatment for caffeine poisoning-induced tachycardia, successfully relieved refractory tachycardia. Then, hemodialysis ultimately eliminated serum caffeine and completely alleviated caffeine-related central nervous system toxicity. We discuss the clinical symptoms, management and toxicodynamics based on the concentration of caffeine and its metabolites in serum and urine.

In Vitro Toxicological Profile of Labetalol-Folic Acid/Folate Co-Administration in H9c2(2-1) and HepaRG Cells.

Background and Objectives: The consumption of dietary supplements has increased over the last decades among pregnant women, becoming an efficient resource of micronutrients able to satisfy their nutritional needs during pregnancy. Furthermore, gestational drug administration might be necessary to treat several pregnancy complications such as hypertension. Folic acid (FA) and folate (FT) supplementation is highly recommended by clinicians during pregnancy, especially for preventing neural tube birth defects, while labetalol (LB) is a ß-blocker commonly administered as a safe option for the treatment of pregnancy-related hypertension. Currently, the possible toxicity resulting from the co-administration of FA/FT and LB has not been fully evaluated. In light of these considerations, the current study was aimed at investigating the possible in vitro cardio- and hepato-toxicity of LB-FA and LB-FT associations. Materials and Methods: Five different concentrations of LB, FA, FT, and their combination were used in myoblasts and hepatocytes in order to assess cell viability, cell morphology, and wound regeneration. Results: The results indicate no significant alterations in terms of cell viability and morphology in myoblasts (H9c2(2-1)) and hepatocytes (HepaRG) following a 72-h treatment, apart from a decrease in the percentage of viable H9c2(2-1) cells (~67%) treated with LB 150 nM−FT 50 nM. Additionally, LB (50 and 150 nM)−FA (0.2 nM) exerted an efficient wound regenerating potential in H9c2(2-1) myoblasts (wound healing rates were >80%, compared to the control at 66%), while LB-FT (at all tested concentrations) induced no significant impairment to their migration. Conclusions: Overall, our findings indicate that LB-FA and LB-FT combinations lack cytotoxicity in vitro. Moreover, beneficial effects were noticed on H9c2(2-1) cell viability and migration from LB-FA/FT administration, which should be further explored.

Isotopic response of labetalol-associated lichen planus pemphigoides on an old radiation site: A case report.

Over the years, the occurrences of different types of skin disorders arising from radiation sites have been observed and studied. Examples include autoimmune blistering diseases such as pemphigus, pemphigoid, and interface or inflammatory reaction patterns such as lichen planus, lupus erythematosus, and Stevens-Johnson syndrome. The phenomenon whereby a new skin disorder arises from a previously healed or irradiated site is called an isotopic response, described as a type of Koebner phenomenon. Ionizing radiation itself can profoundly affect the skin. Both early and late changes can present, which typify the progression of changes following irradiation of the skin. Herein, we report a rare case of labetalol-associated lichen planus pemphigoides that occurred at the site treated with radiation for a soft tissue malignancy after 19 years as a result of an isotopic response. The rash was well-controlled after therapy and kept a 4-year remission. The same skin reaction recurred after the reintroduction of labetalol 4 years later.

Unrecognised pheochromocytoma in pregnancy discovered through metoclopramide-triggered hypertensive emergency.

PURPOSE: Pheochromocytoma, a catecholamine-secreting tumour leading to neurological and cardiovascular life-threatening conditions through hypertension crisis, occurs in 0.1-0.5% of hypertensive patients, but it is extremely rare in pregnancy (0.0018-0.006%). Some classes of drugs, even commonly used in pregnancy, can trigger catecholamine secretion, precipitating the clinical situation. MATERIALS AND METHODS AND RESULTS: We report a 33-year-old woman, gravida 2 para 1, with previous mild hypertension, was admitted to the emergency room, at 28 2/7 weeks of gestation due to headache, tachycardia and severe arterial hypertension (220/120 mm Hg) triggered by the antiemetic metoclopramide used for a week because of nausea. In the emergency room, a paradoxical rise in blood pressure followed intravenous labetalol infusion was observed. Both metoclopramide and labetalol-triggered hypertensive crisis raised the suspicion of an undiagnosed pheochromocytoma. Diagnostic work-up showed elevated normetanephrine urinary excretion ​​and a right adrenal pheochromocytoma by abdominal magnetic resonance imaging. Oral alpha-1 and beta-1-adrenergic antagonist and calcium-channel blocker were started. At 33-weeks of gestation, she underwent a caesarean section giving birth to a female child. Seven weeks later she underwent a video-laparoscopic right adrenalectomy which normalised her blood pressure. CONCLUSIONS: Both metoclopramide, a selective dopamine type-2 receptor antagonist and partial agonist of 5-hydroxytryptamine 4 receptor, and labetalol, a non-selective ß-adrenoreceptor-blocker with weak α1-adrenergic antagonism, exacerbated an acute hypertensive crisis revealing an unrecognised pheochromocytoma in a pregnant patient. Careful attention to potential drug-triggered catecholamine crises and especially early recognition of pheochromocytomas, are mandatory in hypertensive pregnant women. A missed or delayed diagnosis could result in catastrophic results affecting foetal and maternal outcomes.

Treatment of pregnancy-induced hypertension compared with labetalol, low dose aspirin and placebo.

This study aimed to evaluate the maternal and fetal results in women undergoing antihypertensive therapy (low aspirin or labetalol) with mild to severe chronic hypertension relative to women without medicines. This randomized multi-center clinical trial was performed with random division into three groups of 393 pregnant women with mild to moderate chronic hypertension. From the beginning of the pregnancy to the end of the puerperium, the low dosage aspirin group (n = 129), the labetalol group (n = 127), and the drug-free or control group (n = 126) reported both mother and child results. Major variations in the presence of severely motherly hypertension, pre-eclampsia, renal failure, ECG shifts, and cardiovascular rupture between treatment groups (low doses of aspirin and labetalol) and control groups were noted. Repeated placenta and blood pressure control hospitalizations. (P<0.001) in the control group more often (untreated). The new babies were more vulnerable to gestational age (SGA), neonatal hypotension, neonatal Hyperbilirubinemia, and ICU (p <0.001 in contrast with the low-dose aspirin and control groups). In the control group, the proportion of premature babies was considerably higher than in the treatment group (p<0,05). A mild to moderate persistent high blood pressure during pregnancy therapy helps minimize mother and child occurrence. The use of labetalol is correlated with a higher incidence of SGA, neonatal hypotension, and neonatal hyperbilirubinemia relative to low-dose aspirin or control group.

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.

Labetalol Infusion Attenuates Paradoxical Hypertension and Decreases Plasma Renin Activity After Repair of Coarctation of the Aorta in Children.

OBJECTIVE: Paradoxical hypertension after repair of coarctation of the aorta in children is associated with the release of catecholamines and activation of the renin-angiotensin system. The objective of the present study was to describe the effects of labetalol infusion on blood pressure, plasma catecholamine levels, and plasma renin activity in a series of children undergoing repair of coarctation of the aorta. DESIGN: Prospective, observational cohort study. SETTING: Tertiary children's hospital with university affiliation. PARTICIPANTS: The study was comprised of 15 consecutive children older than 1 year undergoing repair of coarctation of the aorta. INTERVENTIONS: Intravenous infusion of labetalol, up to 20 µg/kg/min, was administered when patients became hypertensive after release of the aortic cross-clamp. Supplementation with nitroprusside was allowed as needed. MEASUREMENTS AND MAIN RESULTS: Blood pressure was maintained below baseline values throughout the labetalol infusion. Plasma norepinephrine increased from 160 ± 81 pg/mL (preoperative) to 657 ± 268 pg/mL (6 h after release of aortic cross-clamp). Plasma renin activity decreased from 16.6 ± 9.7 ng/kg/h (at cross-clamp release) to 2.2 ± 2.2 ng/kg/h (6 h after cross-clamp release). Nitroprusside was added for 12 patients, at a highest mean dose of 2.4 ± 2.5 µg/kg/min. CONCLUSIONS: Labetalol inhibited activation of the renin-angiotensin system and helped control paradoxical hypertension after coarctation repair in children.

Oral Nifidepine versus IV labetalol in severe preeclampsia: A randomized control trial.

OBJECTIVE: To compare oral Nifidepine and IV labetalol in terms of rapidity of BP control in severe preeclampsia. METHODS: All patients coming to Services Hospital from March 2017 to February 2019 with diagnosis of severe preeclampsia ≥ 24 weeks gestation were randomized to either receive Nifidepine or Labetalol. Primary outcome measure was time taken to control BP and number of doses required. Secondary outcome measures were side effects of drugs, APGAR score, NICU admission and perinatal mortality. RESULTS: Two hundred four patients were included in trial with 102 patients in each group. Labetalol took 22.6± 13.5minutes and Nifidepine took 22.09± 11.7 minutes to achieve target BP (p>0.05). Labetalol required 2.3± 1.58 doses and Nifidepine 2.2± 1.58 doses to control BP ( p>0.05). No maternal side effects were seen in 86 (84.31%) and 92(90.19%) patients in both groups (p>0.05). Mean gestational age at birth was 34.8 ±2.73weeks in Labetalol and 35.2±2.48 weeks in Nifidepine group (p>0.05). In labetalol group, 43 (42.15%) babies had APGAR Score < 7/10 and 23(22.54%) babies required admission to NICU while in Nifidepine group 42 (41.17%) babies had Apgar score < 7/10 & 30(29.4%) babies were admitted to NICU(p>0.05). There were 21(20.5%) perinatal deaths in labetalol Group-And 19(18.6%) in Nifidepine group (p>0.05). CONCLUSION: Oral Nifidepine and IV labetalol are equally efficacious in controlling BP in patients with severe pre eclampsia without any significant side effects.