Hypertensive Emergency: Parenteral Antihypertensives and Population Data.

PURPOSE OF REVIEW: Review parenteral therapeutic choices in treatment of hypertensive crises by mechanism of action and summarize recent literature on the management of hypertensive crises. RECENT FINDINGS: Recent data have documented the safety and efficacy of labetalol and nicardipine in treatment of hypertensive crises as well as characterized the hypertensive emergency population to a much greater extent. Based on recent data, hypertensive emergencies are seen in 0.5% of all emergency room visits. Ischemic stroke and heart failure/pulmonary edema are the most common forms of organ damage seen in hypertensive emergencies. There are many therapeutic choices in treatment of hypertensive crises with varied mechanisms of action. Large randomized, controlled trial evidence is lacking in this therapeutic area; however, recent data have documented the safety and efficacy of labetalol and nicardipine.

Comparison of outcomes following intravenous magnesium compared with intravenous labetalol and oral nifedipine in 355 pregnant Han Chinese women with preeclampsia.

As per the American College of Obstetricians and Gynecologists in 2013, magnesium sulfate is the gold standard for the management of preeclampsia, but it has a short action time that does not provide stable maintenance of blood pressure. Labetalol is currently recommended as first-line treatment by the national UK guidance. This study included 355 pregnant Han Chinese women with preeclampsia and aimed to compare outcomes following intravenous magnesium compared with intravenous labetalol and oral nifedipine. Women received 4 g intravenous magnesium sulfate followed by the maintenance dose of 1 g/h intravenous magnesium sulfate (MS cohort, n = 104) or intravenous labetalol (LB cohort, n = 115), or oral nifedipine (NF cohort, n = 136). Therapy success: systolic blood pressure ~140 mm Hg and diastolic blood pressure ~90 mm Hg, therapy failure: persistent systolic blood pressure ≥ 160 or diastolic blood pressure ≥ 110 mm Hg after maximum dosage of therapy (EL). Women of all cohorts successfully decreased systolic and diastolic blood pressures at EL as compared to them before therapy conditions (P < .001, for all). At EL, systolic and diastolic blood pressures of women of the LB cohort decreased more than those of women of the MS and NF cohorts (P < .05, for all). Therapy was more successful in women of the LB cohort than those of the NF cohort (107 [93%] vs 112 [82%], P = .0132). More numbers of women were reduced blood pressure after 1 day of therapy from the LB cohort than those of the NF (75 [65%] vs 21 [15%]) and MS (75 [65%] vs 35 [34%]) cohorts (P < .0001 for both). Labetalol-induced tachycardia, bradycardia, and intracranial hemorrhage in pregnant women and respiratory distress syndrome and hypoglycemia in neonates. Intravenous labetalol provides proper reduction of blood pressure in Han Chinese women with preeclampsia but has the risk of undesirable maternal and neonatal adverse effects (Level of Evidence: IV; Technical Efficacy: Stage 4).

Evaluation and Management of Hypertensive Disorders of Pregnancy.

Hypertensive disorders of pregnancy complicate up to 10% of pregnancies and remain the major cause of maternal and neonatal morbidity and mortality. Hypertensive disorders of pregnancy can be classified into four groups depending on the onset of hypertension and the presence of target organ involvement: chronic hypertension, preeclampsia, gestational hypertension, and superimposed preeclampsia on chronic hypertension. Hypertension during pregnancy is associated with a higher risk of cardiovascular disease and kidney failure. Early diagnosis and proper treatment for pregnant women with hypertension remain a priority since this leads to improved maternal and fetal outcomes. Labetalol, nifedipine, methyldopa, and hydralazine are the preferred medications to treat hypertension during pregnancy. In this comprehensive review, we discuss the diagnostic criteria, evaluation, and management of pregnant women with hypertension.

Oral nifedipine may be a preferential option for treating acute severe hypertension during pregnancy: a meta-analysis.

AIM: To compare oral nifedipine and intravenous labetalol in the treatment of acute severe hypertension in pregnancy (SHP). METHODS: The primary outcomes were the required time to achieve target blood pressure (RTATBP), systolic blood pressure (SBP) and diastolic BP (DBP) after treatment, secondary outcomes were the number of doses (NoD) and adverse events (AEs). RESULTS: There was no difference between oral nifedipine and intravenous labetalol in SBP, DBP, and AE. However, oral nifedipine provided less RTATBP and NoD. CONCLUSION: Oral nifedipine was associated with less RTATBP and NoD and otherwise did not differ from intravenous labetalol.

Precipitation of sugammadex with nicardipine and labetalol: A laboratory research.

There is a paucity of clinical data about whether sugammadex forms precipitates with other medications. This laboratory experimental study was performed to determine the drugs that produce precipitates with sugammadex. Samples of 1 ml of sugammadex were prepared in transparent cylinders, to which 1 ml of test drugs (rocuronium, neostigmine, glycopyrrolate, atropine, nitroglycerin, dobutamine, dopamine, epinephrine, vasopressin, norepinephrine, phenylephrine, ephedrine, esmolol, nicardipine, and labetalol) was added. The precipitation reaction was observed visually and via light microscope. The pH of each drugs before and after mixing with sugammadex was measured. White crystals were formed when sugammadex was mixed with nicardipine or labetalol. Sugammadex formed precipitate when mixed with nicardipine or labetalol. Sufficient fluid flushing is required between injections of each drug to prevent these reactions.

A Giant Pheochromocytoma Presenting in Pheochromocytoma Crisis: A Case Report.

Giant pheochromocytomas are rare tumors, with the majority being clinically silent. Clinically manifesting pheochromocytoma can present with symptoms of catecholamine excess, but nonspecific symptoms and variable clinical patterns of hypertension make it difficult to diagnose. Missing the diagnosis can lead to cardiovascular catastrophes like a pheochromocytoma crisis and even death. We report a 45-year-old woman on antihypertensives, repeatedly visiting a hospital for recurrent headaches finally presented in a hypertensive crisis at an emergency department. Management was started along with an injection of labetalol, which led to an unpredicted abrupt blood pressure fall, and was successfully resuscitated. Imaging and plasma metanephrine studies revealed an underlying giant pheochromocytoma, which was cured after successful surgical resection. A high degree of clinical suspicion, elaborate and focused history-taking, and initial ultrasound imaging can guide us toward the early diagnosis of pheochromocytoma. Before the alpha blockade, beta-blockers should not be used in any cases of pheochromocytoma. Keywords: case reports; headache; hypertension; pheochromocytoma.

Cardiac medications in obstetric patients.

PURPOSE OF REVIEW: This review summarizes recent literature, updated safety data, and major clinical considerations for commonly used medications for arrhythmias, heart failure, hypertension, ischemic heart disease, and anticoagulation during pregnancy and lactation. RECENT FINDINGS: Recent studies have shown a benefit to more aggressive treatment of mild chronic hypertension to a blood pressure goal of <140/90 with oral labetalol and nifedipine remaining first-line agents. Aspirin is now routinely used for preeclampsia prevention, while experience with other antiplatelet agents, such as purinergic receptor P2Y G protein-coupled 12 (P2Y12) inhibitors, continues to grow. Data on statin therapy are rapidly changing and recent studies suggest this class may not be associated with fetal harm and can be continued in select cases. SUMMARY: As data regarding medication safety continues to evolve, a multidisciplinary team is needed for full consideration of maternal and fetal risks and benefits. Ongoing studies are needed to improve and expand our understanding of medication safety during pregnancy and lactation.

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).

Identifying Targets to Improve the Management of Severe Hypertension in Pregnancy and Postpartum.

OBJECTIVES: To (1) define quality indicators, (2) describe care gaps, and (3) identify process issues in severe hypertension (sustained systolic blood pressure [BP] ≥160 mm Hg or diastolic BP ≥110 mm Hg) management at our tertiary care centre. METHODS: Pregnant and postpartum persons diagnosed with a hypertensive disorder of pregnancy from 2018 to 2019 were identified. A retrospective cohort of patients with severe hypertension was constructed, and data were collected through chart review. Severe hypertension management was assessed according to defined quality indicators. Clinical characteristics were compared between participants with and without time-to-target BP within 60 minutes. Process issues were examined for each severe hypertension occurrence. RESULTS: Of 608 participants with a hypertensive disorder of pregnancy, 90 (15%) experienced severe hypertension. Median time-to-target BP was 76 minutes (interquartile range 47-123 minutes), and target BP (<155/105 mm Hg) was achieved within 60 minutes in 31/90 (34%) participants. Appropriate antihypertensives for severe hypertension were used in 55/90 (61%), and time-to-treatment initiation was within 30 minutes in 42/54 (78%). Chronic hypertension and oral labetalol use were associated with delays in achieving target BP. Process issues related to severe hypertension management included inappropriate treatment (n = 35/90; 39%), failure to recognize severe hypertension as an emergency (n = 21/90; 23%), and delayed treatment initiation (n = 12/54; 22%). CONCLUSION: We defined quality indicators for severe hypertension management. Time-to-target BP within 60 minutes was achieved in a minority of patients, and chronic hypertension was associated with delayed severe hypertension resolution. Process issues in severe hypertension management were described.

Postpartum medical management of hypertension and risk of readmission for hypertensive complications.

OBJECTIVE: To compare the risk of readmission in those receiving no treatment, labetalol, nifedipine or both at hospital discharge following delivery complicated by presence of hypertension. STUDY DESIGN: Retrospective study at a single tertiary care center over a 4-year period (2017-2020). Those with peripartum hypertension (pHTN), defined as any SBP greater than 140 mmHg or DBP greater than 90 mmHg on two occasions 4 h apart during their admission for delivery were included. The primary outcome was postpartum readmission because of hypertensive complications. Analysis was stratified by medication prescribed at discharge (no treatment prescribed, labetalol, nifedipine, or both). The risks of readmission for the management of pHTN were estimated using logistic regression and adjusted for confounding variables. RESULTS: Nineteen thousand, four hundred and twenty-five women gave birth during the study period and 4660 (24.0%) met the described definition of pHTN. Of those, 1232 (26.4%) were discharged on antihypertensive medication (s). There were 217 (4.7%) readmissions for hypertensive complications following discharge. Compared with patients who did not receive antihypertensive medication at discharge, any nifedipine prescription was found to significantly decrease the risk of readmission: monotherapy [aOR 0.27 (0.15-0.48)], nifedipine with labetalol [aOR 0.35 (0.16-0.77)]. Labetalol monotherapy was associated with increased risk of readmission [aOR 1.66 (1.06-2.61)]. CONCLUSION: The risk of postpartum readmission for hypertensive complication was reduced by 65% when patients were discharged on nifedipine monotherapy and 56% with combined nifedipine and labetalol treatment when compared with no treatment. Patients discharged on labetalol monotherapy were nearly six times as likely to be readmitted for hypertensive complications when compared with patients on nifedipine monotherapy.

Nicardipine versus Labetalol for Hypertension during Acute Stroke: A Systematic Review and Meta-Analysis.

Background and Objective: Current recommendations prescribe either nicardipine or labetalol as the first-line treatment for acute hypertension due to ease of use, availability, and low price. However, it is unclear if these drugs have different effectiveness and safety profiles. This systematic review and meta-analysis aimed to compare the efficacy and safety of labetalol and nicardipine in patients with acute stroke. Materials and Methods: MEDLINE via PubMed, Scopus, Embase, and Google Scholar databases were electronically searched for the eligible publications from inception until March 2022. All full-text journal papers in English which compared the efficacy of nicardipine with that of labetalol on lowering blood pressure (BP; or treating hypertension) in all subtypes of acute stroke were included. The Cochrane Collaboration tool was used to assess the risk of bias. Data were analyzed using specific statistical methods. Results: Following the abstract and full-text screening, this meta-analysis included five retrospective cohorts and one prospective pseudorandomized cohort. Nicardipine's effect on time at goal BP was significantly superior to that of labetalol in patients with acute stroke (0.275 standardized mean difference [SMD], 95% confidence interval [CI]: 0.112-0.438, P = 0.001). The incidence of adverse events was significantly higher in the nicardipine group than that in the labetalol group. The pooled odds ratio (OR) was 1.509 (95% CI: 1.077-2.113, I2 = 0.00%, P = 0.757). The quality of included studies was found to be low. Conclusion: More prospective, comparative trials are needed to investigate the efficacy of BP management as well as clinical outcomes in acute stroke patients receiving continuous labetalol and nicardipine infusions.

Hypertensive Conditions: Hypertensive Disorders in Pregnancy.

Hypertensive disorders in pregnancy (HDP) represent a spectrum of disease that affect women through pregnancy and the immediate postpartum period. These conditions are associated with significant morbidity and mortality during and after pregnancy and have been linked to cardiovascular disease later in life. The HDP spectrum includes gestational hypertension (HTN), preeclampsia, eclampsia, HELLP (hemolysis, elevated liver enzymes, and low platelet count) syndrome, chronic HTN, and chronic HTN with superimposed preeclampsia. Low-dose aspirin is recommended as a preventive drug after 12 weeks' gestation in women who are at high risk of preeclampsia. In HDP, close blood pressure (BP) monitoring, laboratory evaluation, and fetal assessment are warranted. Labetalol and nifedipine extended release are first-line oral antihypertensives for outpatient BP management of chronic HTN; labetalol, hydralazine, and nifedipine immediate release are used for hospitalized patients. HDP may develop or progress in the postpartum period; continued vigilance is important in the puerperium.

Treatment of Post-Coarctectomy Hypertension With Labetalol-A 9-Year Single-Center Experience.

BACKGROUND: Although considering the pathophysiology of post-coarctectomy hypertension, ß-blockers should be effective, experience with labetalol for treatment is limited in the literature. METHODS: Retrospective collection and analysis of data in children aged ≤6 years following coarctectomy in our tertiary care university medical center between January 2009 and June 2018. RESULTS: 96 patients were included, 45 were treated with intravenous labetalol and 51 received no treatment. Median time to maximum dose received (median 1.1 mg/kg/h) was 2.7 h, and median time to the reduction of labetalol dose was 8.3 h. No antihypertensives had to be added. In one child, labetalol was switched to nitroprusside due to bronchoconstriction. Of patients receiving intravenous labetalol, 48% had been switched to oral labetalol at discharge. CONCLUSIONS: Intravenous labetalol is a fast, effective, and safe drug to treat hypertension following aortic coarctation repair. Labetalol is easily converted to oral therapy when the continuation of treatment is considered necessary.

Hypertensive Crisis in Pregnancy.

Severe hypertension in pregnancy is a medical emergency, defined as systolic blood pressure (BP) ≥ 160 mm Hg and/or diastolic BP ≥ 110 mm Hg taken 15 minutes to 4 or more hours apart. Outside pregnancy, acute severe hypertension (HTN) is defined as a BP greater than 180/110 to 120 reproducible on 2 occasions. The lower threshold for severe HTN in pregnancy reflects the increased risk for adverse outcomes, particularly maternal stroke and death, and may be a source of under-recognition and treatment delay, particularly in nonobstetrical health care settings. Once a severe hypertension episode is recognized, antihypertensive therapy should be initiated as soon as feasibly possible, at least within 30 to 60 minutes. Intravenous (IV) labetalol, hydralazine, and oral immediate-release nifedipine are all recommended first-line agents and should be administered according to available institutional protocols and based on provider knowledge and familiarity.

Postpartum Readmission for Hypertension After Discharge on Labetalol or Nifedipine.

OBJECTIVE: To assess whether readmission for hypertension by 6 weeks postpartum differed between patients discharged on nifedipine or labetalol. METHODS: This cohort study included patients with delivery admissions from 2006 to 2017 who were discharged from the hospital on nifedipine or labetalol and were included in a large, national adjudicated claims database. We identified patients' discharge medication based on filled outpatient prescriptions. We compared rates of hospital readmission for hypertension between patients discharged postpartum on labetalol alone, nifedipine alone, or combined nifedipine and labetalol. Patients with chronic hypertension without superimposed preeclampsia were excluded. Comparisons based on medication were performed using logistic regression models with adjustment for prespecified confounders. Comparisons were also stratified by hypertensive disorder of pregnancy severity. RESULTS: Among 1,582,335 patients overall, 14,112 (0.89%) were discharged postpartum on labetalol, 9,001 (0.57%) on nifedipine, and 1,364 (0.09%) on both medications. Postpartum readmissions for hypertension were more frequent for patients discharged on labetalol compared with nifedipine (641 patients vs 185 patients, 4.5% vs 2.1%, adjusted odds ratio [aOR] 1.63, 95% CI 1.43-1.85). Readmissions for hypertension were more frequent for patients discharged on labetalol compared with nifedipine for both mild (4.5% vs 2.7%, aOR 1.57, 95% CI 1.29-1.93) and severe hypertensive disorders of pregnancy (261 patients vs 72 patients, 5.7% vs 3.2%, aOR 1.63, 95% CI 1.43-1.85). Readmissions for hypertension were more frequent on combined nifedipine and labetalol compared with nifedipine (3.1% vs 2.1%), but the odds were lower after confounder adjustment (aOR 0.80, 95% CI 0.64-0.99). CONCLUSION: Postpartum discharge on labetalol was associated with increased risk of readmission for hypertension compared with discharge on nifedipine.

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.

False-positive Fentanyl Urine Detection after Initiation of Labetalol Treatment for Hypertension in Pregnancy: A Case Report.

BACKGROUND: Labetalol hydrochloride (LH) is a pharmacologic treatment for hypertensive disease (HD) in pregnancy. However, for pregnant persons with substance use disorders (SUDs), LH may interfere with urine drug testing. CASE SUMMARY: We present 3 pregnant or postpregnant persons with SUDs who experienced presumptive positive urine immunoassays for fentanyl while prescribed LH for perinatal HD. DISCUSSION: Labetalol hydrochloride treatment for HD in pregnancy can result in presumptive positive urine immunoassays for fentanyl. Unrecognized or misinterpreted, this phenomenon can lead to significant consequences for pregnant and postpartum persons with co-occurring substance use and hypertensive disorders. Clinicians caring for pregnant persons with SUDs must be aware of this phenomenon and its sequelae when ordering and interpreting urine immunoassays for fentanyl.

Race/ethnicity differences in response to acute antihypertensive treatment of peripartum severe hypertension.

BACKGROUND: Hypertensive disorders of pregnancy increase maternal morbidity, mortality, and long-term risk for cardiovascular disease. The rising incidence of chronic hypertension and preeclampsia disproportionately affects people of color. There is a paucity of published data examining differences in the effectiveness of acute antihypertensive agents between pregnant patients of different races/ethnicities. We aimed to determine if the effectiveness of acute antihypertensive agents for peripartum severe hypertension differs by race/ethnicity. METHODS: A retrospective cohort study of patients with severe peripartum hypertension (systolic blood pressure ≥ 160 mmHg and/or diastolic blood pressure ≥ 110 mm Hg confirmed within 15 min) to determine whether the effectiveness of blood pressure control using nationally recommended medications (hydralazine, labetalol, nifedipine) differed by race/ethnicity. The primary outcome was reduction and maintenance of blood pressure to target ranges (140-150/90-100 mm Hg or below) for ≥4 h in each race/ethnicity group. Statistical tests included χ2, Fisher's exact, analysis of variance, and multivariable logistic regression. RESULTS: Of 729 patients receiving treatment for severe peripartum hypertension, all medications were effective (overall 86.4% efficacy) at controlling blood pressure. Labetalol was the most effective medication in White patients (93.0 vs. 74.7% for nifedipine and 86.5% for hydralazine, p < .001). No overall differences in medication effectiveness were found in Black, Asian, or LatinX patients. Black and Asian patients were more likely to experience >1 hypertensive episode [51.0 and 49.0%, respectively vs. 35.4% (White) and 40.0% (LatinX), p = .008]. CONCLUSION: Currently recommended therapies for severe peripartum hypertension are effective in controlling blood pressure for ≥4 h in patients of all race/ethnic groups. Labetalol was the most effective medication in White patients with no overall differences in medication effectiveness in Black, Asian, or LatinX patients.