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The clinical management of aneurysmal subarachnoid hemorrhage (SAH)-associated vasospasm remains a challenge in neurosurgical practice, with its prevention and treatment having a major impact on neurological outcome. While considered a mainstay, nimodipine is burdened by some non-negligible limitations that make it still a suboptimal candidate of pharmacotherapy for SAH. This narrative review aims to provide an update on the pharmacodynamics, pharmacokinetics, overall evidence, and strength of recommendation of nimodipine alternative drugs for aneurysmal SAH-associated vasospasm and delayed cerebral ischemia. A PRISMA literature search was performed in the PubMed/Medline, Web of Science, ClinicalTrials.gov, and PubChem databases using a combination of the MeSH terms "medical therapy," "management," "cerebral vasospasm," "subarachnoid hemorrhage," and "delayed cerebral ischemia." Collected articles were reviewed for typology and relevance prior to final inclusion. A total of 346 articles were initially collected. The identification, screening, eligibility, and inclusion process resulted in the selection of 59 studies. Nicardipine and cilostazol, which have longer half-lives than nimodipine, had robust evidence of efficacy and safety. Eicosapentaenoic acid, dapsone and clazosentan showed a good balance between effectiveness and favorable pharmacokinetics. Combinations between different drug classes have been studied to a very limited extent. Nicardipine, cilostazol, Rho-kinase inhibitors, and clazosentan proved their better pharmacokinetic profiles compared with nimodipine without prejudice with effective and safe neuroprotective role. However, the number of trials conducted is significantly lower than for nimodipine. Aneurysmal SAH-associated vasospasm remains an area of ongoing preclinical and clinical research where the search for new drugs or associations is critical., (© 2024. The Author(s).)

Background: Preeclampsia (PE) is a pregnancy disorder that represents a major cause of maternal and perinatal morbidity and mortality., Methods: This network meta-analysis was registered with PROSPERO. We searched the PubMed, ClinicalTrials.gov. and Embase databases for studies published from inception to the 31 st of March 2023. RevMan5.3 software provided by the Cochrane Collaboration was used for direct meta-analysis (DMA) statistical analysis. Funnel maps, network meta-analysis (NMA), the surface under the cumulative ranking curve (SUCRA) to rank the different interventions and publication bias were generated by STATA 17.0 software., Results: We included eight randomized controlled trials (RCTs) involving a total of 1192 women with PE; two studies were of high quality and six were of moderate quality. Eight interventions were addressed in the NMA. In the DMA, we found that blood pressure in the Ketanserin group were significantly higher than those in the Nicardipine group. NMA showed that blood pressure in the Dihydralazine group was significantly higher than that in the Methyldopa, Labetalol, Nicardipine and Diltiazem groups. And the blood pressure in the Labetalol group was significantly lower than that in the Nicardipine group. SUCRA values showed that Diltiazem was more effective in lowering blood pressure than other drugs looked at in this study., Conclusion: According to the eight RCTs included in this study, Diltiazem was the most effective in reducing blood pressure in PE patients; Labetalol and Nicardipine also had good effects. Diltiazem is preferred for the treatment of patients with severe PE and high blood pressure.

Background: Hypertensive crisis is an acute increase in blood pressure >180/120 mm Hg. A titratable antihypertensive agent is preferred to lower blood pressure acutely in a controlled way and prevent an abrupt overcorrection. Nicardipine and clevidipine are both dihydropyridine calcium channel blockers that provide unique benefits for blood pressure control., Objective: The purpose of this study was to compare the efficacy and safety of nicardipine or clevidipine for blood pressure control in the setting of hypertensive crisis., Methods: This was a single-center, retrospective cohort study. Eligible patients received either nicardipine or clevidipine for the treatment of hypertensive crisis. The primary outcome was achievement of 25% reduction in mean arterial pressure at 1 h. The secondary outcome was achievement of a systolic blood pressure (SBP) of <160 mm Hg at 2-6 h from the start of the infusion., Results: This study included a total of 156 patients, 74 in the nicardipine group and 82 in the clevidipine group. The SBP on admission and at the start of the infusion were similar between groups. There was no difference between groups in achieving a 25% reduction in mean arterial pressure at 1 h. Nicardipine achieved an SBP goal of <160 mm Hg at 2-6 h significantly more often than the clevidipine group (89.2% vs. 73.2%; p = 0.011)., Conclusions: There is no difference between agents for initial blood pressure control in the treatment of hypertensive crisis. Nicardipine showed more sustained SBP control, with a lower risk of rebound hypertension and a significant cost savings compared with clevidipine., Competing Interests: Declaration of competing interest None., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Competing Interests: The authors have disclosed that they do not have any potential conflicts of interest.

Objectives: Postoperative hypertension frequently occurs after surgery for congenital heart disease. Given safety concerns when using calcium channel blockers in infants along with the cost and side-effect profile of nitroprusside, we retrospectively assessed our experience of using nicardipine and nitroprusside for postoperative blood pressure control in infants who underwent surgery for congenital heart disease. We also investigated the cost difference between the medications., Design: This study was a single-center retrospective, pre-post chart review of patients who had surgery for congenital heart disease between 2016 and 2020. The primary aim was a noninferiority comparison of achievement of blood pressure goal at 1-hour post-initiation of an antihypertensive agent. Secondary comparisons included achievement of blood pressure goal at 2 hours after medication initiation, Vasoactive-Inotropic Score (VIS), and blood transfusion, crystalloid volume, and calcium needs., Setting: Academic quaternary-care center., Patients: Infants under 1 year old who required treatment for hypertension with nitroprusside ( n = 71) or nicardipine ( n = 52) within 24 hours of surgery for congenital heart disease., Interventions: None., Measurements and Main Results: We failed to identify any difference in proportion of patients that achieved blood pressure control at 1-hour after medication initiation (nitroprusside 52% vs. nicardipine 54%; p = 0.86), with nicardipine noninferior to nitroprusside within a 15% margin. Of patients who did not achieve control at 1-hour post-medication initiation, receiving nicardipine was associated with blood pressure control at 2 hours post-medication initiation (79% vs. 38%; p = 0.003). We also failed to identify an association between antihypertensive types and mean VIS scores, blood transfusion volumes, crystalloid volumes, and quantities of calcium administered. Index cost of using nitroprusside was 16 times higher than using nicardipine, primarily due to difference in wholesale cost., Conclusions: In our experience of achieving blood pressure control in infants after surgery for congenital heart disease (2016-2020), antihypertensive treatment with nicardipine was noninferior to nitroprusside. Furthermore, nicardipine use was significantly less expensive than nitroprusside. Our contemporary practice is therefore to use nicardipine in preference to nitroprusside., Competing Interests: Dr. Mirea disclosed work for hire. The remaining authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2024 by the Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies.)

Treatment options for Peyronie's disease (PD) remain limited. Topical H100 gel, (Hybrid Medical, Edina, USA), which contains nicardipine, super oxide dismutase and emu oil showed safety and efficacy in a previous small double-blind placebo-controlled pilot study. The present study evaluates if topically applied H100 gel applied to the penile shaft infiltrates the tunica albuginea. Nicardipine is a key active ingredient in H100 and serves as a surrogate marker. Three men already scheduled to undergo a planned surgical procedure for PD applied commercially available H100 gel twice daily to the penile shaft for up to 30 days prior to the procedure. Tunica albuginea samples were obtained at surgery. Nicardipine evaluation was performed using isotope dilution technique via liquid-chromatograph-mass spectrometry (LCMS). All three patients tolerated H100 gel application without side effects. All three tunica albuginea specimens showed detectable nicardipine in the tunical tissue. Transdermal application of commercially available H100 gel is able to penetrate the tunica albuginea tissue and is detectable in men with acute and chronic PD. This finding may support the encouraging results found in the prior H100 pilot study., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

Background: Nicardipine is commonly used in the management of hypertensive crises, except those involving cardiac contractility defects despite its ability to reduce afterload and pulmonary congestion. Consequently, there is limited literature evaluating nicardipine's role for this indication. The purpose of this study was to evaluate the efficacy and safety of nicardipine in adults with reduced ejection fractions presenting with acute heart failure with hypertension (AHF-H)., Methods: This was a retrospective study conducted at an academic Level 1 trauma center with an annual Emergency Department (ED) volume surpassing 100,000. The purpose of this study was to determine the efficacy and safety of nicardipine in adults with reduced ejection fractions presenting to the ED with AHF-H. Efficacy was determined by achievement of the physician prescribed blood pressure target range. The primary safety endpoints included the number of individuals who experienced bradycardia (< 60 beats per minute, bpm) or hypotension (systolic blood pressure, SBP, < 90 mmHg) while receiving nicardipine and for up to 15 min after its discontinuation. Patients were included if they were ≥ 18 years of age, received a continuous intravenous nicardipine infusion within six hours of presenting to the ED, and had an ejection fraction ≤ 40% per an echocardiogram obtained within three months of the study visit. Pregnant and incarcerated patients were excluded., Results: Of the 500 patient charts reviewed, 38 met inclusion criteria. The median (interquartile, IQR) ejection fraction and brain natriuretic peptide (BNP) were 35% (25-40) and 731 pg/nL (418-3277), respectively. The median baseline heart rate and SBP were 90 bpm and 193 mmHg, respectively. The median physician specified SBP goal was 160 mmHg and all patients met this endpoint in a median time of 18 min. One (2.6%) patient in the total population developed both hypotension and bradycardia. This patient had an ejection fraction of 20%, was intubated, and received nicardipine in addition to esmolol for an aortic dissection without experiencing an adverse event until 30 min after dexmedetomidine was initiated., Conclusion: In this non-interventional study evaluating the use of nicardipine in patients with reduced ejection fractions presenting to the ED with AHF-H, nicardipine was found to be safe and effective. To our knowledge this is the largest study to date evaluating nicardipine in this patient population and positively contributes to the existing literature., Competing Interests: Declaration of Competing Interest The authors declare no relevant conflicts of interest or financial relationships., (Copyright © 2023 Elsevier Inc. All rights reserved.)

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., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: It is imperative to develop novel therapeutics to overcome chemoresistance, a significant obstacle in the clinical management of prostate cancer (PCa) and other cancers., Methods: A phenotypic screen was performed to identify novel inhibitors of chemoresistant PCa cells. The mechanism of action of potential candidate(s) was investigated using in silico docking, and molecular and cellular assays in chemoresistant PCa cells. The in vivo efficacy was evaluated in mouse xenograft models of chemoresistant PCa., Results: Nicardipine exhibited high selectivity and potency against chemoresistant PCa cells via inducing apoptosis and cell cycle arrest. Computational, molecular, and cellular studies identified nicardipine as a putative inhibitor of embryonic ectoderm development (EED) protein, and the results are consistent with a proposed mechanism of action that nicardipine destabilised enhancer of zeste homologue 2 (EZH2) and inhibited key components of noncanonical EZH2 signalling, including transducer and activator of transcription 3, S-phase kinase-associated protein 2, ATP binding cassette B1, and survivin. As a monotherapy, nicardipine effectively inhibited the skeletal growth of chemoresistant C4-2B-TaxR tumours. As a combination regimen, nicardipine synergistically enhanced the in vivo efficacy of docetaxel against C4-2 xenografts., Conclusion: Our findings provided the first preclinical evidence supporting nicardipine as a novel EED inhibitor that has the potential to be promptly tested in PCa patients to overcome chemoresistance and improve clinical outcomes., (© 2023. The Author(s), under exclusive licence to Springer Nature Limited.)

Objective: The primary objective of this study was to compare the efficacy of clevidipine to nicardipine in the treatment of perioperative acute hypertension in patients undergoing cardiac surgery. Methods: This was a single-center retrospective study which included patients who received either clevidipine or nicardipine. Patients were followed for the duration of study drug infusion or for a maximum of 48 hours. Outcomes assessed included the percent of time spent within patient specific goal blood pressure, incidence of hypertensive events per patient, safety outcomes, and cost of medication treatment. Results: There were 201 cardiac surgeries performed between August 2018-January 2019 and July 2019-February 2020. Sixty-seven patients met our inclusion criteria of receiving either clevidipine (n = 29) or nicardipine (n = 38). The median percent of time spent within goal blood pressure range for clevidipine was 55.2% compared to 36.4% for nicardipine treatment ( P = .036). The median number of hypertensive episodes per patient was 3 for clevidipine and 2 for nicardipine ( P = .211). There were no identified differences in safety outcomes such as hypotension, vasopressor use, serum creatinine elevation, tachycardia, and atrial fibrillation. The median cost of treatment required for the observed 48-hour period with clevidipine was $128.58 compared to $55.74 for nicardipine ( P < .001). Conclusion: Our findings suggest that patients undergoing cardiac surgery on clevidipine had better perioperative blood pressure control compared to nicardipine, with a negligible increase in cost, and no observed difference in safety.

Purpose: The term "cerebrovascular diseases (CVDs)" refers to a broad category of diseases that affect the brain's blood vessels and cerebral circulation. Controlling acute hypertension (HTN) by antihypertensive drugs such as clevidipine and nicardipine can be a highly efficient method of lowering the incidence of CVDs., Methods: This is a systematic review and meta-analysis study. The PubMed, Scopus, and Web of Science online databases and a gray literature search were performed to identify potentially eligible studies. The included studies were observational studies that compared adult patients receiving clevidipine or nicardipine for controlling HTN in the setting of CVD., Results: We reviewed 5 final included articles, including 546 patients. The pooled standardized mean difference (SMD) for time to goal SBP was - 0.04 (95 % CI: [-0.66; 0.58], p-value: 0.86, I 2 : 79.0 %, pooled MD: -12.90 min), meaning that the clevidipine group had a shorter time to goal systolic blood pressure (SBP) than the nicardipine group. The pooled SMD for total volume infusion was - 0.52 (95 % CI: [-0.93; -0.12], p-value: 0.03, I 2 : 0.0 %, pooled MD: -1118.81 mL), showing a notably lower total volume infused into patients in the clevidipine group., Conclusions: We found that clevidipine reaches the SBP goal faster than nicardipine; however, there was no statistically significant difference between the two drugs. The total volume infused to achieve the goal SBP was significantly lower in the clevidipine group. Further prospective studies are needed to compare clevidipine and nicardipine in CVD patients on a large scale., Competing Interests: Declaration of Competing Interest We disclose that Ali Seifi is a member of the speakers’ bureau of Chiesi Pharmaceutical and the inventor and patent holder of HiccAway. All other authors have no conflicts of interest., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Aim: This systematic review aimed to shed light on the efficacy of intracoronary (IC) nicardipine in treating no reflow with CAD undergoing revascularization. Methods: Literature search was performed on databases with following eligibility criteria: adult patients with CAD; clinical trials or observational studies; IC nicardipine as intervention; therapeutic and safety outcome reported. Results: A total of 1249 papers were yielded during the literature search. Of these, 11 studies were finalized for this systematic review. Complete restoration of TIMI 3 flow was observed in 98.6% of the patients receiving IC nicardipine. A significant increase in the CBF after infusion of IC nicardipine (p < 0.05) was also observed. Conclusion: IC nicardipine significantly increases CBF and decreases coronary vascular resistance.

Purpose: Intra-arterial (IA) infusion of calcium channel blockers (CCBs) has been widely applied in treating medically refractory vasospasm; however, surprisingly little is known regarding their vasodilatory duration. This study was undertaken to compare attributes of nicardipine and dantrolene, focusing on efficacy and capacity for sustained vasodilation., Methods: In New Zealand white rabbits (N = 22), vasospasm was individually provoked through experimentally induced subarachnoid hemorrhage and confirmed via conventional angiography, grouping animals by IA-infused drug (nicardipine vs. dantrolene). Controls received normal saline. After chemoangioplasty, follow-up angiography was performed at intervals of 1-3 h for 6 h to compare vasospastic and dilated (i.e., treated) arterial diameters. Drug efficacy, duration of action, and changes in mean arterial pressure (relative to baseline) were analyzed by group., Results: Compared with controls, effective vasodilation was evident in both nicardipine and dantrolene test groups after IA infusion. Vasodilatory effects of nicardipine peaked at 1 h, returning to former vasospastic states at 3 h. In dantrolene recipients, vasodilation endured longer, lasting >6 h. Only the nicardipine group showed a significant 3‑h period of lowered blood pressure., Conclusion: Unlike the vasodilatory action of a CCB, sustained for < 3 h after IA infusion, the effect of dantrolene endured for > 6 h. This outcome suggests that IA dantrolene infused alone or together with a conventional CCB infusion may be a new means of prolonging vasodilatory effect. Further research is needed to assess durations of IA-infused vasodilatory drug based on perfusion status., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany.)

Background: On the basis of increased mortality associated with hyperchloremia among critically ill patients, we investigated the effect of occurrence of early hyperchloremia on death or disability at 90 days in patients with intracerebral hemorrhage (ICH)., Methods: We analyzed the data from Antihypertensive Treatment of Cerebral Hemorrhage 2 trial, which recruited patients with spontaneous ICH within 4.5 h of symptom onset. Patients with increased serum chloride levels (110 mmol/L or greater) at either baseline or 24, 48, or 72 h after randomization were identified. We further graded hyperchloremia into one occurrence or two or more occurrences within the first 72 h. Two logistic regression analyses were performed to determine the effects of hyperchloremia on (1) death within 90 days and (2) death or disability at 90 days after adjustment for potential confounders., Results: Among the total of 1,000 patients analyzed, hyperchloremia within 72 h was seen in 114 patients with one occurrence and in 154 patients with two or more occurrences. Patients with one occurrence of hyperchloremia (odds ratio [OR] 2.5, 95% confidence interval [CI] 1.1-5.5) and those with two or more occurrences (OR 2.6, 95% CI 1.3-5.0) had significantly higher odds of death within 90 days after adjustment for age, race and ethnicity, National Institutes of Health Stroke Scale score strata, hematoma volume, presence or absence of intraventricular hemorrhage, cigarette smoking, previous stroke, and maximum hourly dose of nicardipine. Patients with two or more occurrences of hyperchloremia (OR 3.4, 95% CI 2.1-5.6) had significantly higher odds of death or disability at 90 days compared with patients without hyperchloremia after adjustment for the abovementioned potential confounders., Conclusions: The independent association between hyperchloremia and death or disability at 90 days suggests that avoidance of hyperchloremia may reduce the observed death or disability in patients with ICH., Clinical Trial Registration: ClinicalTrials.gov: NCT01176565., (© 2022. Springer Science+Business Media, LLC, part of Springer Nature and Neurocritical Care Society.)

Background: Neurocritical management of aneurysmal subarachnoid hemorrhage focuses on delayed cerebral ischemia (DCI) after aneurysm repair., Methods: This study conceptualizes the pathophysiology of cerebral ischemia and its management using a brain oxygen-directed protocol (intracranial pressure [ICP] control, eubaric hyperoxia, hemodynamic therapy, arterial vasodilation, and neuroprotection) in patients with subarachnoid hemorrhage, undergoing aneurysm clipping (n = 40)., Results: The brain oxygen-directed protocol reduced Lbo 2 (Pbto 2 [partial pressure of brain tissue oxygen] <20 mm Hg) from 67% to 15% during acute brain attack (<24 hours of ictus), by increasing Pbto 2 from 11.31 ± 9.34 to 27.85 ± 6.76 (P < 0.0001) and then to 29.09 ± 17.88 within 72 hours. Day-after-bleed, Fio 2 change, ICP, hemoglobin, and oxygen saturation were predictors for Pbto 2 during early brain injury. Transcranial Doppler ultrasonography velocities (>20 cm/second) increased at day 2. During DCI caused by territorial sonographic vasospasm (TSV), middle cerebral artery mean velocity (V m ) increased from 45.00 ± 15.12 to 80.37 ± 38.33/second by day 4 with concomitant Pbto 2 reduction from 29.09 ± 17.88 to 22.66 ± 8.19. Peak TSV (days 7-12) coincided with decline in Pbto 2 . Nicardipine mitigated Lbo 2 during peak TSV, in contrast to nimodipine, with survival benefit (P < 0.01). Intravenous and cisternal nicardipine combination had survival benefit (Cramer Φ = 0.43 and 0.327; G 2 = 28.32; P < 0.001). This study identifies 4 zones of Lbo 2 during survival benefit (Cramer Φ = 0.43 and 0.3) TSV, uncompensated; global cerebral ischemia, compensated, and normal Pbto 2 . Admission Glasgow Coma Scale score (not increased ICP) was predictive of low Pbto 2 (β = 0.812, R 2 = 0.661, F 1,30 = 58.41; P < 0.0001) during early brain injury. Coma was the only credible predictor for mortality (odds ratio, 7.33/>4.8∗; χ 2 = 7.556; confidence interval, 1.70-31.54; P < 0.01) followed by basilar aneurysm, poor grade, high ICP and Lbo 2 during TSV. Global cerebral ischemia occurs immediately after the ictus, persisting in 30% of patients despite the high therapeutic intensity level, superimposed by DCI during TSV., Conclusions: We propose implications for clinical practice and patient management to minimize cerebral ischemia., (Copyright © 2022 Elsevier Inc. All rights reserved.)

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, I 2 = 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., Competing Interests: None

Introduction: Women with severe hypertension during pregnancy require prompt stabilization with a combination of magnesium sulfate and rapidly acting intravenously administered antihypertensives. It remains unknown which antihypertensive is best suited for pregnancy. The present study evaluated the intravenous use of the calcium antagonist, nicardipine., Material and Methods: This multicenter, retrospective case series included all pregnant women beyond 20 weeks of gestation with severe antepartum hypertension that were treated with intravenous nicardipine., Primary Outcome Measures: successful treatment, time to successful treatment, and maternal safety. Severe hypertension was defined as systolic blood pressure (SBP) of 160 mm Hg or more and/or diastolic blood pressure (DBP) of 110 mm Hg or more., Results: This study included 830 women. After 1 h of treatment, two-thirds of the women had SBP below 160 mm Hg and DBP below 100 mm Hg. In three out of four women, the mean arterial pressure was below 120 mm Hg. Within 2 h of treatment, 77.4% of women achieved successful treatment. In all cases, nicardipine was eventually effective. Within the first 2 h, 42.7% of women experienced temporary low DBP (ie below 70 mm Hg) without clinical consequences for the mother or fetus. In all cases, the low DBP resolved after discontinuing or reducing the dosage of nicardipine. One case of fetal distress was attributable to maternal hypotension, and a cesarean section was performed at more than 2 h after initiating therapy. During treatment, headache, nausea, and vomiting decreased significantly., Conclusions: To date, this was the largest case-series study on the use of nicardipine for treating severe antepartum hypertension in pregnancy. We found that nicardipine could effectively and safely treat this condition. Based on its high success rate and acceptable safety profile, nicardipine should be considered a first-line treatment in women with severe hypertension in pregnancy., (© 2022 The Authors. Acta Obstetricia et Gynecologica Scandinavica published by John Wiley & Sons Ltd on behalf of Nordic Federation of Societies of Obstetrics and Gynecology (NFOG).)

Background: Aneurysmal subarachnoid hemorrhage (aSAH) is associated with high mortality and morbidity. We aimed to determine the relative benefits of pharmacological prophylactic treatments in patients with aneurysmal subarachnoid hemorrhage by performing a network meta-analysis of randomized trials., Methods: We searched Medline, Web of Science, Embase, Scopus, ProQuest, and Cochrane Central to February 2020. Pairs of reviewers independently identified eligible trials, extracted data, and assessed the risk of bias. Eligible trials compared the prophylactic effects of any oral or intravenous medications or intracranial drug-eluting implants to one another or placebo or standard of care in adult hospitalized patients with confirmed aneurysmal subarachnoid hemorrhage. We used the GRADE (Grading of Recommendations Assessment, Development and Evaluation) approach to assess the certainty of the evidence., Results: We included 53 trials enrolling 10 415 patients. Nimodipine likely reduces all-cause mortality compared to placebo (odds ratio [OR],0.73 [95% CI, 0.53-1.00]; moderate certainty; absolute risk reduction (ARR), -3.35%). Nimodipine (OR, 1.46 [95% CI, 1.07-1.99]; high certainty; absolute risk increase, 8.25%) and cilostazol (OR, 3.73 [95% CI, 1.14-12.18]; moderate certainty; absolute risk increase, 23.15%) were the most effective treatments in improving disability at the longest follow-up. Compared to placebo, clazosentan (10 mg/kg; OR, 0.39 [95% CI, 0.22-0.68]; high certainty; ARR, -16.65%), nicardipine (OR, 0.48 [95% CI, 0.24-0.94]; moderate certainty; ARR, -13.70%), fasudil (OR, 0.55 [95% CI, 0.31-0.98]; moderate certainty; ARR, -11.54%), and magnesium (OR, 0.66 [95% CI, 0.46-0.94]; high certainty; ARR, -8.37%) proved most effective in reducing the likelihood of delayed cerebral ischemia., Conclusions: Nimodipine and cilostazol are likely the most effective treatments in preventing morbidity and mortality in patients with aneurysmal subarachnoid hemorrhage. Clazosentan, nicardipine, fasudil, and magnesium showed beneficial effects on delayed cerebral ischemia and vasospasm but they were not found to reduce mortality or disability. Future trials are warranted to elaborately investigate the prophylactic effects of medications that may improve mortality and long-term functional outcomes, such as cilostazol and clazosentan., Registration: URL: https://www.crd.york.ac.uk/PROSPERO/; Unique identifier: CRD42019122183.

Background and Aims: Nicardipine has strong, rapidly acting antihypertensive activity. The effects of acute systolic blood pressure levels achieved with intravenous nicardipine after onset of intracerebral hemorrhage on clinical outcomes were determined., Methods: A systematic review and individual participant data analysis of articles before 1 October 2020 identified on PubMed were performed (PROSPERO: CRD42020213857). Prospective studies involving hyperacute intracerebral hemorrhage adults treated with intravenous nicardipine whose outcome was assessed using the modified Rankin Scale were eligible. Outcomes included death or disability at 90 days, defined as the modified Rankin Scale score of 4-6, and hematoma expansion, defined as an increase ≥6 mL from baseline to 24-h computed tomography., Summary of Review: Three studies met the eligibility criteria. For 1265 patients enrolled (age 62.6 ± 13.0 years, 484 women), death or disability occurred in 38.2% and hematoma expansion occurred in 17.4%. Mean hourly systolic blood pressure during the initial 24 h was positively associated with death or disability (adjusted odds ratio (aOR) 1.12, 95% confidence interval (CI) 1.00-1.26 per 10 mmHg) and hematoma expansion (1.16, 1.02-1.32). Mean hourly systolic blood pressure from 1 h to any timepoint during the initial 24 h was positively associated with death or disability. Later achievement of systolic blood pressure to ≤140 mmHg increased the risk of death or disability (aOR 1.02, 95% CI 1.00-1.05 per hour)., Conclusions: Rapid lowering of systolic blood pressure by continuous administration of intravenous nicardipine during the initial 24 h in hyperacute intracerebral hemorrhage was associated with lower risks of hematoma expansion and 90-day death or disability without increasing serious adverse events.

Background: Intracranial hemorrhage is associated with high mortality and morbidity. Lowering systolic blood pressure (SBP) with an intravenous antihypertensive, such as nicardipine or clevidipine, may reduce the risk of hematoma expansion and rebleeding. Previous studies comparing nicardipine and clevidipine in patients with stroke found no significant difference in blood pressure management. The inclusion of patients with ischemic stroke limited those studies because of convoluted results related to faster door-to-needle times. The purpose of this study was to compare clevidipine with nicardipine in time to goal SBP in hemorrhagic stroke., Methods: This single-center retrospective observational cohort study evaluated adult hemorrhagic patients with stroke who received clevidipine or nicardipine from January 1, 2015, to December 31, 2020. Patients were excluded if they had trauma-related hemorrhage, received concurrent continuous intravenous antihypertensives, received the study drug for less than 1-h duration, had a less than 24-h washout period between agents, required any dialysis, were pregnant, or were incarcerated. The primary outcome was time to goal SBP. Secondary outcomes included need for additional antihypertensives, percentage of time at goal SBP, all-cause mortality, 30-day readmission, rebleeding, total volume of antihypertensive infusion, hematoma expansion, intensive care unit length of stay (LOS), hospital LOS, and cost of infusion. Safety outcomes included hypotension, severe hypotension, rebound hypertension, bradycardia, tachycardia, onset of atrial fibrillation, and acute kidney injury., Results: Of 89 patients included in this study, 60 received nicardipine and 29 received clevidipine. There was no significant difference between nicardipine and clevidipine in time to goal SBP in the unmatched cohort (30 vs. 45 min; p = 0.73) or the propensity-score-matched cohort (30 vs. 45 min; p = 0.47). Results were not affected by potential confounders in the multiple linear regression. The nicardipine group had a higher total volume from infusion compared with the clevidipine group (1410 vs. 330 mL; p < 0.0001) but significantly lower cost ($99.6 vs. $497.4; p < 0.0001). There were no significant differences in need for additional antihypertensives, percentage of time at goal SBP, all-cause mortality, 30-day readmission, rebleeding, hematoma expansion, intensive care unit LOS, and hospital LOS. Compared with the clevidipine group, the nicardipine group had less rebound hypertension (40% vs. 75.9%; p = 0.0017) and less bradycardia (23.3% vs. 44.8%; p = 0.05). There were no significant differences in hypotension, severe hypotension, tachycardia, and acute kidney injury., Conclusions: In patients with hemorrhagic stroke, nicardipine appeared to have similar efficacy as clevidipine in SBP reduction, with a more likely reduction of rebound hypertension and drug cost. This retrospective study was underpowered, which may limit these implications. Further prospective studies are warranted to confirm these results., (© 2021. Springer Science+Business Media, LLC, part of Springer Nature and Neurocritical Care Society.)

One of the challenges in bringing new therapeutic agents (since nimodipine) in for the treatment of cerebral ischemia associated with aneurysmal subarachnoid hemorrhage (aSAH) is the incongruence in therapeutic benefit observed between phase II and subsequent phase III clinical trials. Therefore, identifying areas for improvement in the methodology and interpretation of results is necessary to increase the value of phase II trials. We performed a systematic review of phase II trials that continued into phase III trials, evaluating a therapeutic agent for the treatment of cerebral ischemia associated with aSAH. We followed the Preferred Reporting Items for Systematic reviews and Meta-Analyses guidelines for systematic reviews, and review was based on a peer-reviewed protocol (International Prospective Register of Systematic Reviews no. 222965). A total of nine phase III trials involving 7,088 patients were performed based on eight phase II trials involving 1558 patients. The following therapeutic agents were evaluated in the selected phase II and phase III trials: intravenous tirilazad, intravenous nicardipine, intravenous clazosentan, intravenous magnesium, oral statins, and intraventricular nimodipine. Shortcomings in several design elements of the phase II aSAH trials were identified that may explain the incongruence between phase II and phase III trial results. We suggest the consideration of the following strategies to improve phase II design: increased focus on the selection of surrogate markers of efficacy, selection of the optimal dose and timing of intervention, adjustment for exaggerated estimate of treatment effect in sample size calculations, use of prespecified go/no-go criteria using futility design, use of multicenter design, enrichment of the study population, use of concurrent control or placebo group, and use of innovative trial designs such as seamless phase II to III design. Modifying the design of phase II trials on the basis of lessons learned from previous phase II and phase III trial combinations is necessary to plan more effective phase III trials., (© 2021. Springer Science+Business Media, LLC, part of Springer Nature and Neurocritical Care Society.)

Background: With the increasing use of magnetic resonance imaging in the assessment of acute intracerebral hemorrhage, diffusion-weighted imaging hyperintense lesions have been recognized to occur at sites remote to the hematoma in up to 40% of patients. We investigated whether blood pressure reduction was associated with diffusion-weighted imaging hyperintense lesions in acute intracerebral hemorrhage and whether such lesions are associated with worse clinical outcomes by analyzing imaging data from a randomized trial., Methods: We performed exploratory subgroup analyses in an open-label randomized trial that investigated acute blood pressure lowering in 1000 patients with intracerebral hemorrhage between May 2011 and September 2015. Eligible participants were assigned to an intensive systolic blood pressure target of 110-139 mm Hg versus 140-179 mm Hg with the use of intravenous nicardipine. Of these, 171 patients had requisite magnetic resonance imaging sequences for inclusion in these subgroup analyses. The primary outcome was the presence of diffusion-weighted imaging hyperintense lesions. Secondary outcomes included death or disability and serious adverse event at 90 days., Results: Diffusion-weighted imaging hyperintense lesions were present in 25% of patients (mean age 62 years). Hematoma volume > 30 cm 3 was an adjusted predictor (adjusted relative risk 2.41, 95% confidence interval 1.00-5.80) of lesion presence. Lesions occurred in 25% of intensively treated patients and 24% of standard treatment patients (relative risk 1.01, 95% confidence interval 0.71-1.43, p = 0.97). Patients with diffusion-weighted imaging hyperintense lesions had similar frequencies of death or disability at 90 days, compared with patients without lesions., Conclusions: Randomized assignment to intensive acute blood pressure lowering did not result in a greater frequency of diffusion-weighted imaging hyperintense lesion. Alternative mechanisms of diffusion-weighted imaging hyperintense lesion formation other than hemodynamic fluctuations need to be explored. Clinical trial registration ClinicalTrials.gov (Ref. NCT01176565; https://clinicaltrials.gov/ct2/show/NCT01176565 )., (© 2021. Springer Science+Business Media, LLC, part of Springer Nature and Neurocritical Care Society.)

Background and Objective: The clinical effect of renal impairment on intracerebral hemorrhage (ICH) is unknown. This study sought to assess whether estimated glomerular filtration rate (eGFR) affects clinical outcomes or modifies the efficacy of intensive systolic blood pressure (BP) control (target, 110-139 mm Hg) against the standard (target, 140-179 mm Hg) among patients with ICH., Methods: We conducted post hoc analyses of ATACH-2, a randomized, 2-group, open-label trial. The baseline eGFR of each eligible patient was calculated using the Chronic Kidney Disease Epidemiology Collaboration equation. The outcome of interest was death or disability at 90 days. Multivariate logistic regression models were used for analysis., Results: Among the 1,000 patients randomized, 974 were analyzed. The median baseline eGFR was 88 (interquartile range, 68, 99) mL/min/1.73 m 2 ; 451 (46.3%), 363 (37.3%), and 160 (16.4%) patients had baseline eGFR values of ≥90, 60-89, and <60 mL/min/1.73 m 2 , respectively. Compared with normal eGFR (≥90 mL/min/1.73 m 2 ), higher odds of death or disability were noted among those with eGFR values of <60 mL/min/1.73 m 2 (adjusted odds ratio [OR], 2.02; 95% confidence interval [CI], 1.25-3.26) but not among those with eGFR values of 60-89 mL/min/1.73 m 2 (OR, 1.01; 95% CI, 0.70-1.46). The odds of death or disability were significantly higher in the intensive arm among patients with decreased eGFR; the ORs were 0.89 (95% CI, 0.55-1.44), 1.13 (0.68-1.89), and 3.60 (1.47-8.80) in patients with eGFR values of ≥90, 60-89, and <60 mL/min/1.73 m 2 , respectively ( p for interaction = 0.02)., Discussion: Decreased eGFR is associated with unfavorable outcomes following ICH. The statistically significant interaction between the eGFR group and treatment assignment raised safety concerns for the intensive BP-lowering therapy among patients with renal impairment., Trial Registration Information: Clinicaltrials.gov identifier: NCT01176565., Classification of Evidence: This study provides Class II evidence that in spontaneous ICH, decreased eGFR identifies patients at risk of death or disability following intensive BP control., (Copyright © 2021 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.)

Objective: Cerebral vasospasm and delayed cerebral ischemia (DCI) contribute to poor outcome following subarachnoid hemorrhage (SAH). With the paucity of effective treatments, the authors describe their experience with intrathecal (IT) nicardipine for this indication., Methods: Patients admitted to the Emory University Hospital neuroscience ICU between 2012 and 2017 with nontraumatic SAH, either aneurysmal or idiopathic, were included in the analysis. Using a propensity-score model, this patient cohort was compared to patients in the Subarachnoid Hemorrhage International Trialists (SAHIT) repository who did not receive IT nicardipine. The primary outcome was DCI. Secondary outcomes were long-term functional outcome and adverse events., Results: The analysis included 1351 patients, 422 of whom were diagnosed with cerebral vasospasm and treated with IT nicardipine. When compared with patients with no vasospasm (n = 859), the treated group was significantly younger (mean age 51.1 ± 12.4 years vs 56.7 ± 14.1 years, p < 0.001), had a higher World Federation of Neurosurgical Societies score and modified Fisher grade, and were more likely to undergo clipping of the ruptured aneurysm as compared to endovascular treatment (30.3% vs 11.3%, p < 0.001). Treatment with IT nicardipine decreased the daily mean transcranial Doppler velocities in 77.3% of the treated patients. When compared to patients not receiving IT nicardipine, treatment was not associated with an increased rate of bacterial ventriculitis (3.1% vs 2.7%, p > 0.1), yet higher rates of ventriculoperitoneal shunting were noted (19.9% vs 8.8%, p < 0.01). In a propensity score comparison to the SAHIT database, the odds ratio (OR) to develop DCI with IT nicardipine treatment was 0.61 (95% confidence interval [CI] 0.44-0.84), and the OR to have a favorable functional outcome (modified Rankin Scale score ≤ 2) was 2.17 (95% CI 1.61-2.91)., Conclusions: IT nicardipine was associated with improved outcome and reduced DCI compared with propensity-matched controls. There was an increased need for permanent CSF diversion but no other safety issues. These data should be considered when selecting medications and treatments to study in future randomized controlled clinical trials for SAH.

Objectives: The aim of this study was to compare radial arterial catheter-derived pressure with oscillometric blood pressure in women with severe peripartum hypertension undergoing urgent treatment with intravenous nicardipine at a maternal intensive care unit., Study Design: We obtained patients' paired values of systolic blood pressure (SBP), diastolic blood pressure (DBP) and mean arterial pressure (MAP). All of the measurements were divided into four groups based on the levels of SBP and MAP measured using the oscillometric method., Main Outcome Measures: We assessed agreements of the paired values using the Bland-Altman method. The clinical relevance of differences between the two methods was assessed by error grid analysis., Results: A total of 337 paired SBP and DBP values and 305 paired MAP values were obtained for 89 patients. The values of intra-arterial SBP were higher than those of oscillometric SBP. The values of intra-arterial MAP were higher than those of oscillometric MAP except for the women with MAP ≥ 125 mm Hg. Bland - Altman analysis showed acceptable agreement for DBP and MAP measured by intra-arterial method and oscillometric method. Error grid analysis showed the proportions of measurements in risk zones A to E were 83.22%, 16.46%, 0.32%, 0%, and 0% for SBP, and 97.81%, 2.19%, 0%, 0%, and 0% for MAP, respectively., Conclusion: Intra-arterial MAP can be used reliably to monitor the effect of intravenous nicardipine for treating severe hypertension. Intra-arterial SBP may trigger moderate-risk treatment decisions in the women with oscillometric SBP ≤ 160 mm Hg., (Copyright © 2021 International Society for the Study of Hypertension in Pregnancy. Published by Elsevier B.V. All rights reserved.)

Objective: To compare the impact of intensive blood pressure (BP) lowering right after intracerebral hemorrhage (ICH) on clinical and hematoma outcomes among patients from different geographic locations, we performed a prespecified subanalysis of a randomized, multinational, 2-group, open-label trial to determine the efficacy of rapidly lowering BP in hyperacute ICH (Antihypertensive Treatment of Acute Cerebral Hemorrhage [ATACH]-2), involving 537 patients from East Asia and 463 recruited outside of Asia., Methods: Eligible patients were randomly assigned to a systolic BP target of 110 to 139 mm Hg (intensive treatment) or 140 to 179 mm Hg (standard treatment). Predefined outcomes were poor functional outcome (modified Rankin Scale score 4-6 at 90 days), death within 90 days, hematoma expansion at 24 hours, and cardiorenal adverse events within 7 days., Results: Poor functional outcomes (32.0% vs 45.9%), death (1.9% vs 13.3%), and cardiorenal adverse events (3.9% vs 11.2%) occurred significantly less frequently in patients from Asia than those outside of Asia. The treatment-by-cohort interaction was not significant for any outcomes. Only patients from Asia showed a lower incidence of hematoma expansion with intensive treatment (adjusted relative risk [RR] 0.56, 95% confidence interval [CI] 0.38-0.83). Both Asian (RR 3.53, 95% CI 1.28-9.64) and non-Asian (RR 1.71, 95% CI 1.00-2.93) cohorts showed a higher incidence of cardiorenal adverse events with intensive treatment., Conclusions: Poor functional outcomes and death 90 days after ICH were less common in patients from East Asia than those outside of Asia. Hematoma expansion, a potential predictor for poor clinical outcome, was attenuated by intensive BP lowering only in the Asian cohort., Clinicaltrialsgov Identifier: NCT01176565., Classification of Evidence: This study provides Class II evidence that, for patients from East Asia with ICH, intensive blood pressure lowering significantly reduces the risk of hematoma expansion., (Copyright © 2020 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.)

Background: Elevated blood pressure (BP) is pervasive among patients that visit emergency departments (EDs) for their care., Methods: In this review article, we outline the current approach to the management of these individuals and highlight the crucial role emergency medicine clinicians play in reducing the morbidity associated with elevated BP., Results: We highlight the critical importance of immediate treatment when elevated BP contributes to new or worsening end-organ injury but emphasize that such hypertensive emergencies are rare. For the vast majority of patients with elevated BP in the ED who do not have new or worsening end-organ injury from elevated BP, immediate BP reduction within the ED is not recommended or safe. Nonetheless, within weeks after an ED visit, there is a pressing need to improve the care of patients with elevated or previously undiagnosed hypertension. For many, it may be their only regular point of engagement with the healthcare system. To address this, we present novel perspectives that envision a new role for emergency medicine in chronic hypertension management-one that acknowledges the significant population-level gaps in BP control that contribute to disparities in cardiovascular disease and sets the stage for future changes in systems-based practice., Conclusions: Emergency medicine plays a key and evolving role in reducing morbidity associated with elevated BP., (© The Author(s) 2020. Published by Oxford University Press on behalf of American Journal of Hypertension, Ltd.)

Objective: To develop a nicardipine prolonged-release implant (NPRI) to prevent cerebral vasospasm in patients with subarachnoid hemorrhage in 1999, which may be used during craniotomy, and report the results of our recent 12-year single critical care center experience., Methods: Of 432 patients with aneurysmal subarachnoid hemorrhage treated between 2007 and 2019, 291 were enrolled. 97 Patients were aged >70 years (33%), 194 were female (67%), 138 were World Federation of Neurological Societies grades 1, 2, and 3 (47%), 218 were Fisher group 3 (75%), and 243 had an anterior circulation aneurysm (84%). Using a propensity score matching method for these five factors, the severity of cerebral vasospasm, occurrence of delayed cerebral infarction, and modified Rankin Scale (mRS) score at discharge were analyzed., Results: One hundred patients each with or without NPRI were selected, and the ratios of coil/clip were 0/100 and 88/12, respectively. Cerebral vasospasm and delayed cerebral infarction were both significantly less common in the NPRI group (p=0.004, OR=0.412 (95% CI 0.223 to 0.760) and p=0.005, OR=0.272 (95% CI 0.103 to 0.714, respectively); a significant difference was seen in the mRS score at discharge by Fisher's exact test (p=0.0025). A mRS score of 6 (dead) was less common in the group with NPRI, and mRS scores of 0 and 1 were also less common. No side effects were seen., Conclusions: NPRIs significantly reduced the occurrence of cerebral vasospasm and delayed cerebral infraction without any side effects. The NPRI and non-NPRI groups showed different patterns of short-term outcomes in the single critical care center, which might have been due to selection bias and patient characteristics. Differences in outcomes may become clear in comparisons with patients treated by craniotomy., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. No commercial re-use. See rights and permissions. Published by BMJ.)

Background/objective: Intravenous nicardipine infusion is effective for rapid blood pressure control. However, its use requires hemodynamic monitoring in the intensive care unit (ICU) and is associated with high hospital cost. This study aimed to examine the effect of early versus late initiation of oral antihypertensives on ICU length of stay (LOS) and cost of hospitalization in patients with hypertensive intracerebral hemorrhage (ICH)., Methods: This is a single-center retrospective study of patients with hypertensive ICH treated with nicardipine infusion from January 1, 2013, to December 31, 2017. Patients were dichotomized into study and control groups, based on receiving oral antihypertensives within 24 h versus after 24 h of emergency department arrival. Baseline characteristics, duration of nicardipine infusion, LOS in the ICU and hospital, functional outcome at discharge, and hospital cost were compared between the two groups using univariate and multivariate analysis., Results: A total of 90 patients in the study group and 76 in the control group were identified. There was no significant difference in demographics, past medical history, and initial SBP between the two groups. After adjusting for confounding factors with multivariate regression models, early initiation of oral antihypertensives was associated with significant reductions in duration of nicardipine infusion (55.5 ± 60.1 vs 121.6 ± 141.3 h, p <0.005), nicardipine cost ($14,207 vs $29,299, p < 0.01), ICU LOS (2 vs 5 days, p < 0.005), and cost of hospitalization ($24,564 vs $47,366, p < 0.01). There was no significant difference in adversary renal events, favorable outcomes, and mortality between the two groups., Conclusions: Early initiation of oral antihypertensives is safe and may have a significant financial impact on patients with hypertensive ICH.

Background: Vasoactive medications are commonly administered for afterload reduction and arterial hypertension treatment in patients after cardiac surgery. A systematic review and meta-analysis were conducted to determine the effects of sodium nitroprusside and nicardipine on hemodynamics and cardiac performance in this population., Methods: A systematic review of published manuscripts was performed to identify studies of patients who received sodium nitroprusside and nicardipine as part of the treatment for arterial hypertension or afterload reduction after cardiac surgery. A meta-analysis was then conducted to determine the effects of sodium nitroprusside and nicardipine on hemodynamics and cardiac performance. The following parameters were captured: blood pressure, heart rate, right atrial pressure, systemic vascular resistance, and stroke volume., Results: In total, five studies with 571 patients were pooled for these analyses. Systolic blood pressure, diastolic blood pressure, and mean arterial blood pressure were similar in both groups. The cardiac index was greater with nicardipine while mean pulmonary artery pressure was lower with sodium nitroprusside., Conclusion: Nicardipine and sodium nitroprusside have similar abilities in reducing afterload in the postoperative cardiac population. Statistically significant differences were found in pulmonary artery pressure and cardiac index. It may be beneficial to consider nicardipine for afterload reduction in patients with a low cardiac index., (© 2020 Wiley Periodicals, Inc.)

The worldwide incidence of coronavirus disease 2019 (COVID-19) infection is rapidly increasing, but there exists limited information on coronavirus disease 2019 in pregnancy. Here, we present our experience with 7 confirmed cases of coronavirus disease 2019 in pregnancy presenting to a single large New York City tertiary care hospital. Of the 7 patients, 5 presented with symptoms of coronavirus disease 2019, including cough, myalgias, fevers, chest pain, and headache. Of the 7 patients, 4 were admitted to the hospital, including 2 who required supportive care with intravenous hydration. Of note, the other 2 admitted patients who were asymptomatic on admission to the hospital, presenting instead for obstetrically indicated labor inductions, became symptomatic after delivery, each requiring intensive care unit admission., (© 2020 Elsevier Inc. All rights reserved.)

New evidence and increased use of intracranial devices have increased the frequency of intraventricular (IVT) medication administration in the neurologic intensive care unit. Significant benefits and risks are associated with administration of medications directly into the central nervous system. This review summarizes important literature, along with key information for clinicians regarding the administration, dosing, monitoring, and adverse effects related to IVT medication usage. Multiple medications have supporting literature for their use in critically ill patients including amphotericin B, aminoglycosides, colistimethate, daptomycin, quinupristin/dalfopristin, vancomycin, alteplase, and nicardipine. Sterile preparation and delivery, along with different types of devices that support medication administration, are also reviewed. One randomized, placebo-controlled trial of alteplase demonstrated decreased mortality but no change in good functional outcome. Other reports of IVT medication use are mainly limited to case reports and retrospective case series. There is a need for increased research on the topic; however, several practical barriers decrease the likelihood of a large, placebo-controlled, prospective study for most indications. Providers should consider implementing protocols to maximize safety of IVT medication delivery to ensure optimal patient outcomes.

Background: It is not clear whether subsets of patients with intracerebral hemorrhage (ICH) benefit from intensive blood pressure (BP) lowering. We evaluated whether white matter hyperintensities (WMH) burden influences response to this therapy., Methods: Retrospective secondary analysis of the Antihypertensive Treatment of Acute Cerebral Hemorrhage 2 trial. Patients were randomized to intensive (systolic BP target: 110-139 mmHg) versus standard (systolic BP target: 140-179 mmHg) BP treatment with intravenous nicardipine within 4.5 h from onset between May 2011 and September 2015. WMH were rated on magnetic resonance images (fluid-attenuated inversion recovery sequences), defining moderate-severe WMH as total Fazekas scale score ≥ 3 (range 0-6). The main outcome was death or major disability at 90 days (modified Rankin scale ≥ 3). The secondary outcome was ICH expansion, defined as hematoma growth > 33% from baseline to follow-up CT scan. Predictors of the outcomes of interest were explored with multivariable logistic regression., Results: A total of 195/1000 patients had MRI images available for analysis, of whom 161 (82.6%) had moderate-severe WMH. When compared to patients with none-mild WMH, those with moderate-severe WMH did not have an increased risk of death or major disability (adjusted relative risk: 1.83, 95% CI 0.71-4.69) or ICH expansion (adjusted relative risk: 1.14, 95% CI 0.38-3.37). WMH burden did not modify the effect of intensive BP treatment on outcome (all p for interaction ≥ 0.2)., Conclusion: The majority of acute ICH patients have moderate-severe WMH, but advanced small vessel disease burden marked by WMH does not influence ICH-related outcomes or response to intensive BP reduction.

Perioperative hypertension is a common occurrence in the neurosurgical population, where 60% to 90% of the patients require treatment for blood pressure (BP) control. Nicardipine and clevidipine have been commonly used in neurocritical settings. This retrospective, observational study assessed the effectivity of the administration of clevidipine after nicardipine treatment failure in neurosurgical patients.We retrospectively reviewed the medical charts of adult patients who were admitted to our neurosurgical department and received clevidipine after nicardipine treatment failure for the control of BP. The primary effectivity outcome was the comparison of the percentage of time spent at targeted SBP goals during nicardipine and clevidipine administration, respectively.A total of 12 adult patients treated with clevidipine after nicardipine treatment failure and were included for data analysis. The median number of events that required dose-titration was 20.5 vs 17 during the administration of nicardipine and clevidipine, respectively (P = .534). The median percentage of time spent at targeted SBP goal was 76.2% during the administration of nicardipine and 93.4% during the administration of clevidipine (P = .123).Our study suggests that clevidipine could be an alternative effective drug with an acceptable benefit/risk ratio in the neurosurgical population that fails to achieve BP control with nicardipine treatment.

Background and Aim of the Study: In vitro studies have shown a reduction in radial artery spasm with the use of calcium antagonists. The purpose of this study was to evaluate the efficacy of topical treatment of the radial artery conduit using either verapamil or nicardipine before the anastomoses., Methods: This prospective randomized study included 131 patients, who underwent coronary artery bypass grafting surgery with the use of the radial artery as a conduit. In 65 patients, the harvested radial artery was topically treated with verapamil and in 66 patients with nicardipine. After harvesting the radial artery, the direct flow through the conduit was measured in vitro before 5-minute incubation in nicardipine or verapamil and measured again after incubation. The flow before and after incubation was compared. Postincubation flow was also compared in the two groups. After performing the anastomosis, the flow through the radial artery was measured in vivo., Results: The mean flow after NaCl incubation was 19.93 ± 12.66 mL/min and after incubation in the Ca+ channel blocker 47.16 ± 14.58 mL/min (P < .001). No significant difference in postincubation free flow was found between verapamil (46.29 ± 15.43 mL/min) and nicardipine (48.01 ± 13.77 mL/min; P = .503)., Conclusion: Topical treatment with Ca+ channel blockers reduces radial artery spasm and significantly increases the free flow through the radial artery conduit. Nicardipine is a safe and effective alternative of verapamil in preventing spasm of radial artery conduit., (© 2019 Wiley Periodicals, Inc.)

Intrathecal nicardipine has been shown to have some efficacy for the treatment of symptomatic cerebral vasospasm in aneurysmal subarachnoid hemorrhage (aSAH). We performed a PRISMA-based systematic review of intrathecal nicardipine for the treatment of cerebral vasospasm in aneurysmal subarachnoid hemorrhage. A total of 825 articles were reviewed. After duplicates were removed and the search criteria was applied, 9 articles remained that were eligible for inclusion and analysis. 377 patients received a total of 6,596 injections of intrathecal nicardipine for aSAH-related cerebral vasospasm. The cumulative ventriculostomy-associated infection risk was 6%. Intrathecal nicardipine injections for aSAH-related cerebral vasospasm appears efficacious and safe. Administration of 4 mg of nicardipine every 12 hours was the most commonly reported dosing regimen. Intrathecal nicardipine decreases mean flow velocities on transcranial Doppler and reduces angiographic and clinical vasospasm. The infection risk appears to be in-line with studies in which rates of EVD-related infections have been reported.

Background and Purpose- It is unknown whether blood pressure (BP) reduction influences secondary brain injury in spontaneous intracerebral hemorrhage (ICH). We tested the hypothesis that intensive BP reduction is associated with decreased perihematomal edema expansion rate (PHER) in deep ICH. Methods- We performed an exploratory analysis of the ATACH-2 randomized trial (Antihypertensive Treatment of Acute Cerebral Hemorrhage-2). Patients with deep, supratentorial ICH were included. PHER was calculated as the difference in perihematomal edema volume between baseline and 24-hour computed tomography scans divided by hours between scans. We used regression analyses to determine whether intensive BP reduction was associated with PHER and if PHER was associated with poor outcome (3-month modified Rankin Scale score 4-6). We then used interaction analyses to test whether specific deep location (basal ganglia versus thalamus) modified these associations. Results- Among 1000 patients enrolled in ATACH-2, 870 (87%) had supratentorial, deep ICH. Of these, 780 (90%) had neuroimaging data (336 thalamic and 444 basal ganglia hemorrhages). Baseline characteristics of the treatment groups remained balanced (P>0.2). Intensive BP reduction was associated with a decrease in PHER in univariable (β= -0.15; 95% CI, -0.26 to -0.05; P=0.007) and multivariable (β=-0.12; 95% CI, -0.21 to -0.02; P=0.03) analyses. PHER was not independently associated with outcome in all deep ICH (odds ratio, 1.14; 95% CI, 0.93-1.41; P=0.20), but this association was modified by the specific deep location involved (multivariable interaction P=0.02); in adjusted analyses, PHER was associated with poor outcome in basal ganglia (odds ratio, 1.42; 1.05-1.97; P=0.03) but not thalamic (odds ratio, 1.02; 95% CI, 0.74-1.40; P=0.89) ICH. Conclusions- Intensive BP reduction was associated with decreased 24-hour PHER in deep ICH. PHER was not independently associated with outcome in all deep ICH but was associated with poor outcome in basal ganglia ICH. PHER may be a clinically relevant end point for clinical trials in basal ganglia ICH.

Intracerebral hemorrhage (ICH) is responsible for approximately 15% of strokes annually in the United States, with nearly 1 in 3 of these patients dying without ever leaving the hospital. Because this disproportionate mortality risk has been stagnant for nearly 3 decades, a main area of research has been focused on the optimal strategies to reduce mortality and improve functional outcomes. The acute hypertensive response following ICH has been shown to facilitate ICH expansion and is a strong predictor of mortality. Rapidly reducing blood pressure was once thought to induce cerebral ischemia, though has been found to be safe in certain patient populations. Clinicians must work quickly to determine whether specific patient populations may benefit from acute lowering of systolic blood pressure (SBP) following ICH. This review provides nurses with a summary of the available literature on blood pressure control following ICH. It focuses on intravenous and oral antihypertensive medications available in the United States that may be utilized to acutely lower SBP, as well as medications outside of the antihypertensive class used during the acute setting that may reduce SBP.

Background: The discovery that voltage-gated calcium channel genes such as CACNA1C are part of the aetiology of psychiatric disorders has rekindled interest in the therapeutic potential of L-type calcium channel (LTCC) antagonists. These drugs, licensed to treat hypertension and angina, have previously been used in bipolar disorder, but without clear results. Neither is much known about the broader effects of these drugs on the brain and behaviour., Methods: The Oxford study of Calcium channel Antagonism, Cognition, Mood instability and Sleep (OxCaMS) is a high-intensity randomised, double-blind, placebo-controlled experimental medicine study on the effect of the LTCC antagonist nicardipine in healthy young adults with mood instability. An array of cognitive, psychiatric, circadian, physiological, biochemical and neuroimaging (functional magnetic resonance imaging and magnetoencephalography) parameters are measured during a 4-week period, with randomisation to drug or placebo on day 14. We are interested in whether nicardipine affects the stability of these measures, as well as its overall effects. Participants are genotyped for the CACNA1C risk polymorphism rs1006737., Discussion: The results will clarify the potential of LTCC antagonists for repurposing or modification for use in psychiatric disorders in which cognition, mood and sleep are affected., Trial Registration: ISRCTN, ISRCTN33631053 . Retrospectively registered on 8 June 2018 (applied 17 May 2018).

Objective: The objective of this review was to determine the effectiveness of intrathecal nicardipine compared to usual care on cerebral vasospasm and its impact on the following outcome measures: mean flow velocities, angiographic and/or clinical vasospasm, and infection rates., Introduction: The results of non-traumatic (aneurysmal) subarachnoid hemorrhage can have devastating effects on patients in terms of functional outcomes. Although other medications have been and continue to be used, Nimodipine is the only Food and Drug Administration-approved medication for treating and improving outcomes following non-traumatic subarachnoid hemorrhage, which may be caused by aneurysmal rupture or arteriovenous malformation. Cerebral vasospasm after non-traumatic subarachnoid hemorrhage is a major concern; cerebral vasospasm refers to the narrowing of the cerebral vessels, which can lead to stroke. Delayed ischemic neurological deficit, as a result of cerebral vasospasm, is the number one reason for death and disability following subarachnoid hemorrhage. This review will determine the effects that intrathecal nicardipine has on cerebral vasospam following non-traumatic subarachnoid hemorrhage., Inclusion Criteria: The participants of this review included adult patients (18 years and over) in intensive care units. The patients must have had a subarachnoid hemorrhage without history of trauma as cause of subarachnoid hemorrhage, along with the presence of an external ventricular drain. The intervention was administration of intrathecal nicardipine in patients with cerebral vasospasm as a result of non-traumatic subarachnoid hemorrhage. The comparator was usual care, which does not include use of intrathecal nicardipine as part of the treatment regimen. The current review considered both experimental and quasi-experimental study designs. The primary outcomes measured included presence of cerebral vasospasm (identified by mean flow velocities measured by transcranial Doppler and the presence of angiographic vasospasm identified on angiogram) and clinical/symptomatic vasospasm. Secondarily, infection rates as a result of intrathecal nicardipine administration were evaluated., Methods: The search strategy aimed to find both published and unpublished studies. Seven databases were searched with no date limitations due to the limited amount of research on this topic.Two independent reviewers assessed the methodological validity of the papers prior to inclusion in the review using the standardized critical appraisal instruments from Joanna Briggs Institute System for the Unified Management, Assessment and Review of Information (JBI SUMARI).Quantitative data was extracted from included studies using the standardized data extraction tool from JBI SUMARI.Statistical pooling was not possible; therefore findings were presented in a narrative form., Results: Two studies examined the effect that intrathecal nicardipine has on cerebral vasospasm, clinical/symptomatic vasospasm and safety concerns (i.e. infection). The studies indicate that intrathecal nicardipine has shown potential benefits and safety in the treatment of cerebral vasospasm., Conclusions: Although intrathecal nicardipine has shown potential to be effective in treating cerebral vasospasm, variance existed among those who received intrathecal nicardipine. In terms of safety, one study had no occurrences of associated bacterial meningitis and the other study had two reported cases of bacterial meningitis out of 50 among those who received intrathecal nicardipine. Limited studies on the use of intrathecal nicardipine following non-traumatic subarachnoid hemorrhage and lack of pooling of results for this review demonstrate the need for more research in this field.

Sodium nitroprusside (SNP) is a generically available and rapid-acting intravenous (IV) vasodilator that has been used clinically for decades. Prior to 2013, the cost of SNP was relatively low, and SNP was an affordable option for the treatment of acute hypertension. However, from 2013 to 2017, average wholesale prices for SNP rose to as high as US$900 per vial, earning the drug its status as a "hyperinflation drug." Hyperinflation drugs pose a significant challenge for pharmacy departments. A multidisciplinary effort involving stakeholders from many backgrounds, including pharmacists, physicians, and nurses, is key to developing an effective cost containment strategy. A therapeutic interchange, wherein a drug with similar efficacy is substituted for another, is often an appropriate strategy to address rising drug costs. Fortunately, alternative drugs with a solid evidence base exist for the management of acute hypertension. The dihydropyridine calcium channel blockers, clevidipine and nicardipine, are IV titratable antihypertensive agents with favorable pharmacokinetic and safety profiles. Various studies indicate that clevidipine and nicardipine are effective alternatives to SNP for indications including hypertensive crisis and postoperative hypertension. Some hospitals have reported significant cost savings without adverse outcomes by substituting clevidipine or nicardipine for SNP. This article is intended to serve as a review of the evidence for clevidipine and nicardipine as potential substitutes for SNP and to provide strategies to successfully implement this therapeutic interchange.

Background and Purpose: In acute stroke, hypertension worsens outcomes. Guidelines do not mention a preferred antihypertensive agent. This present study aimed to compare the efficacy and safety of nicardipine and clevidipine in acute stroke., Methods: This retrospective review compared nicardipine with clevidipine for hypertension in acute stroke patients from March 17, 2015 to December 23, 2016. Ischemic and hemorrhagic stroke types were evaluated. Patients were excluded if under 18 years, had traumatic brain injury, had intracranial neoplasm, were on dialysis, had both study drugs during the stroke admission, or the study drug was infused for less than 1 hour. Efficacy outcomes were: time to goal blood pressure, percent time in goal, blood pressure range, and need for additional antihypertensive agents during the infusion. A composite of in-hospital death, 30-day readmission, rebleeding, ischemic to hemorrhagic conversion, and hematoma expansion were compared. Other clinical outcomes included length of intensive care unit and hospital stay, hypotension, bradycardia, tachycardia, onset of atrial fibrillation, and acute kidney injury., Results: Mean time to goal blood pressure was 65.5 minutes and 65.8 minutes in the nicardipine and clevidipine group, respectively (P = .83). No efficacy outcome was significantly different between 2 groups after multivariate analysis., Conclusions: Both nicardipine and clevidipine are reasonable antihypertensive agents in stroke, although cost and volume restriction could differentiate preference., (Copyright © 2018 National Stroke Association. Published by Elsevier Inc. All rights reserved.)

Posterior reversible encephalopathy syndrome (PRES) is a neurological disorder characterised by parieto-occipital vasogenic oedema seen on MRI. Infection and sepsis has been reported as a possible cause for this disorder.We present a 19-year-old immunocompetent Caucasian man with known type 1 diabetes mellitus who presented to the emergency department with acute onset of bilateral visual loss, headaches and hypertension; he had been discharged 2 weeks ago for severe diabetic ketoacidosis and Staphylococcus aureus bacteraemia. Initial CT scan of the head was negative, but MRI showed findings suggestive of PRES. He was treated with nicardipine drip for strict blood pressure management and symptoms resolved within 4 days. PRES is a rare disease that has been increasingly reported as MRI becomes more commonplace. Usually associated with immunological disease, pre-eclampsia and cytotoxic therapies but an association with sepsis due to gram-positive bacteria., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2018. No commercial re-use. See rights and permissions. Published by BMJ.)

Background and Purpose: We compared the rates of death or disability, defined by modified Rankin Scale score of 4 to 6, at 3 months in patients with intracerebral hemorrhage according to post-treatment systolic blood pressure (SBP)-attained status., Methods: We divided 1000 subjects with SBP ≥180 mm Hg who were randomized within 4.5 hours of symptom onset as follows: SBP <140 mm Hg achieved or not achieved within 2 hours; subjects in whom SBP <140 mm Hg was achieved within 2 hours were further divided: SBP <140 mm Hg for 21 to 22 hours (reduced and maintained) or SBP was ≥140 mm Hg for at least 2 hours during the period between 2 and 24 hours (reduced but not maintained)., Results: Compared with subjects without reduction of SBP <140 mm Hg within 2 hours, subjects with reduction and maintenance of SBP <140 mm Hg within 2 hours had a similar rate of death or disability (relative risk of 0.98; 95% confidence interval, 0.74-1.29). The rates of neurological deterioration within 24 hours were significantly higher in reduced and maintained group (10.4%; relative risk, 1.98; 95% confidence interval, 1.08-3.62) and in reduced but not maintained group (11.5%; relative risk, 2.08; 95% confidence interval, 1.15-3.75) compared with reference group. The rates of cardiac-related adverse events within 7 days were higher among subjects with reduction and maintenance of SBP <140 mmHg compared to subjects without reduction (11.2% versus 6.4%)., Conclusions: No decline in death or disability but higher rates of neurological deterioration and cardiac-related adverse events were observed among intracerebral hemorrhage subjects with reduction with and without maintenance of intensive SBP goals., Clinical Trial Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT01176565., (© 2018 American Heart Association, Inc.)

OBJECTIVE Intravenous nicardipine is commonly used for blood pressure reduction in patients with acute stroke. However, few studies have described its effects on cerebrovascular hemodynamics as measured by transcranial Doppler (TCD) waveform analysis and pulsatility index (PI). In this study, the authors report examples of a consistent but paradoxical finding associated with nicardipine that suggests intracranial vasoconstriction, contrary to what is expected from a vasodilator. METHODS The data presented are from a convenience sample of patients who underwent TCD monitoring before, after, or during nicardipine administration. In each case, TCD waveform morphologies and PIs were compared. RESULTS The TCD waveforms during nicardipine infusion are characterized by a prominent systolic peak and dicrotic notch. Systolic deceleration was more pronounced and PIs were significantly elevated in patients who were on nicardipine (p < 0.001). This finding was not evident when patients were not on nicardipine. CONCLUSIONS This study provides the first evidence of paradoxical intracranial vasoconstriction associated with intravenous nicardipine. In the authors' experience, this finding is consistently encountered in the vast majority of patients who are treated with intravenous nicardipine, and is contradictory to what is expected from a vasodilator. Future studies are needed to confirm this finding in larger populations and diverse clinical settings and to examine mechanisms that explain this phenomenon.

Background: Control of postoperative hypertension is central to the care of infants and children after cardiac operations. Continuous pharmacologic delivery affords the advantage of rapid onset and ease of titration. Although well established in older children and adults, calcium channel blockers are routinely avoided in children aged younger than 1 year secondary to concerns of safety and efficacy in the setting of sarcoplasmic reticulum development. Thus, the purpose of this study was to review a single-institution experience with nicardipine, a selective calcium channel blocker, in pediatric patients after cardiac operations., Methods: Children undergoing cardiac operations at the University of Virginia from 2010 to 2015 were retrospectively reviewed after selection based on receipt of nicardipine for blood pressure management in the postoperative period. Demographic, operative, laboratory, and postoperative data were collected for adverse effect analysis and outcomes comparisons between infants aged younger than 6 months (group 1) and older than 6 months (group 2)., Results: During the study period, 68 children (group 1: n = 33 [48%]; group 2: n = 35 [52%]) received nicardipine after cardiac operations (0.5 to 1 μg · kg -1 · min -1 ). Nicardipine was initiated at a mean of 6.6 ± 13.1 hours postoperatively in group 1 and 5.4 ± 7.8 hours in group 2. Nine patients (13%) demonstrated clinically significant hypotension necessitating dosing titration with no statistically significant differences between groups. No major adverse events occurred following nicardipine administration., Conclusions: Nicardipine is well tolerated after cardiac operations in children irrespective of age or underlying pathology. Thus, nicardipine should be considered as safe and effective in children of all ages for control of hypertension after cardiac operations., (Copyright © 2018 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Background: A subarachnoid clot is the strongest predictor of cerebral vasospasm. Our purpose was to analyze the relationship between the number of postoperative cisternal clots and cerebral vasospasm and to assess the efficacy of surgical clot removal., Methods: The subjects were 158 patients with aneurysmal subarachnoid hemorrhage. All patients underwent clipping with cisternal clot removal. The preoperative and postoperative number of clots was analyzed semiquantitatively using computed tomography, and cerebral vasospasm and its severity were analyzed using magnetic resonance angiography in a blind fashion. Factors related to cerebral vasospasm and poor outcome were analyzed retrospectively. Poor outcome was defined as modified Rankin Scale (mRS) score of 3 or greater., Results: Symptomatic cerebral vasospasm (SCV) was observed in 6 patients (3.8%). Angiographic vasospasm (AVS) was observed in 38 patients (24.1%). One year after the operation, 82.9% of patients had an mRS score of 0-2. The postoperative number of clots was significantly (P < 0.005) related to SCV (adjusted odds ratio [OR], 6.447; 95% confidence interval [CI], 2.063-20.146), AVS (OR, 2.634; 95% CI, 1.467-4.728), and poor outcome (OR, 2.103; 95% CI, 1.104-4.007). Poor outcome was also related to age over 65 (OR, 6.658; 95% CI, 2.389-18.559) and World Federation of Neurosurgical Societies scale grade (OR, 1.732; 95% CI, 1.248-2.403)., Conclusions: Surgically removing as many clots as possible in the acute stage can decrease SCV and reduce AVS severity. Irrigation should be performed on all approachable cisterns., (Copyright © 2017 Elsevier Inc. All rights reserved.)