Hypoxia Associated With Dihydropyridine Calcium Channel Inhibitors: A Pharmacovigilance Study in VigiBase.

Due to their negative effects on hypoxic pulmonary vasoconstriction, dihydropyridine calcium channel inhibitors (DCCIs) can lead to hypoxia in patients with a pulmonary shunt. To date, only preclinical studies and case reports have focused on this potential adverse drug reaction. We aimed to assess the reporting association between DCCIs and hypoxia using the World Health Organization pharmacovigilance database (VigiBase). We performed a disproportionality analysis to evaluate the strength of the reporting association between i.v. clevidipine and nicardipine, thought to be a surrogate of patients in the intensive care unit, and hypoxia. The information component and the lower end of its 95% credibility interval were used to evaluate disproportionality. A description of the cases was made. Secondary outcomes included the association between all DCCIs and hypoxia compared with other treatments with similar indications, urapidil and labetalol, regardless of the route of administration. Association between oral nicardipine and hypoxia was also searched. A statistically significant signal of hypoxia was found for intravenous clevidipine and nicardipine. The time to onset was reported with a median of 2 days (interquartile range 1.5-4.5). Four dechallenges were performed with intravenous nicardipine, leading to the resolution of the symptoms. Regardless of the route of administration, a signal of hypoxia was also found for nimodipine but not for other drugs, including comparators. For nicardipine no signal of hypoxia was found with the oral route of administration. Our pharmacovigilance database analysis showed a significant association between the use of intravenous DCCIs and hypoxia.

Intravenous nicardipine for Japanese patients with acute intracerebral hemorrhage: an individual participant data analysis.

The effects of acute systolic blood pressure levels achieved with continuous intravenous administration of nicardipine for Japanese patients with acute intracerebral hemorrhage on clinical outcomes were determined. A systematic review and individual participant data analysis of articles were performed based on prospective studies involving adults developing hyperacute intracerebral hemorrhage who were treated with intravenous nicardipine. 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 or more from baseline to 24 h computed tomography. Of the total 499 Japanese patients (age 64.9 ± 11.8 years, 183 women, initial BP 203.5 ± 18.3/109.1 ± 17.2 mmHg) studied, death or disability occurred in 35.6%, and hematoma expansion occurred in 15.6%. Mean hourly systolic blood pressure during the initial 24 h was positively associated with death or disability (adjusted odds ratio 1.25, 95% confidence interval 1.03-1.52 per 10 mmHg) and hematoma expansion (1.49, 1.18-1.87). These odds ratios were relatively high as compared to the reported ones for overall global patients of this individual participant data analysis [1.12 (95% confidence interval 1.00-1.26) and 1.16 (1.02-1.32), respectively]. In conclusion, lower levels of systolic blood pressure by continuous intravenous nicardipine were associated with lower risks of hematoma expansion and 90-day death or disability in Japanese patients with hyperacute intracerebral hemorrhage. The impact of systolic blood pressure lowering on better outcome seemed to be stronger in Japanese patients than the global ones.

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.

Nicardipine Is a Safe, Efficacious, and Cost-Effective Antihypertensive for Neonates and Young Infants Undergoing Cardiac Surgery.

OBJECTIVE: The use of nicardipine in congenital cardiac surgery has been guarded given the calcium sensitivity of immature myocardium and paucity of clinical data. Reports of nicardipine use have excluded neonates with single ventricles. The goal of this study was to compare the use of nicardipine and sodium nitroprusside for postoperative blood pressure control in young patients recovering from cardiac surgery. METHODS: All neonates (<30 days) and young infants (31-180 days) who received either sodium nitroprusside or nicardipine as first-line therapy for blood pressure control were retrospectively reviewed. Some patients had multiple index operations and each index operation was counted separately regarding treatment with sodium nitroprusside or nicardipine. RESULTS: A total of 59 patients underwent 70 procedures (24 as neonates and 46 as infants). Nicardipine was administered as initial therapy following 33 procedures (n = 28 patients), and sodium nitroprusside was administered as initial therapy following 37 index procedures (n = 31 patients). The duration of treatment was longer (P = .025) when sodium nitroprusside was the initial treatment. Five (15%) patients that received nicardipine required a second blood pressure management agent, and seven (19%) patients that received sodium nitroprusside required a second agent (P = .66). No adverse events related to titratable antihypertensive therapy were recorded in any treatment group. The use of nicardipine resulted in significant medication cost reduction. Based on average wholesale price, patient costs for sodium nitroprusside use were $182,952 ($5,544/pt), while costs for nicardipine were only $24,960 ($780/pt). CONCLUSIONS: Nicardipine can be safely used as a first-line antihypertensive in infants. The use of nicardipine as initial antihypertensive therapy rather than sodium nitroprusside can lead to a significant reduction in medication costs without jeopardizing clinical outcomes.

Initial antihypertensive agent effects on acute blood pressure after intracerebral haemorrhage.

INTRODUCTION: Current guidelines recommend blood pressure (BP) lowering in patients after acute intracerebral haemorrhage (ICH) without guidance on initial choice of antihypertensive class. This study sought to determine if initial antihypertensive class differentially effects acute BP lowering in a large multiethnic ICH cohort. METHODS: Subjects enrolled in the Ethnic/Racial Variations in ICH study between August 2010 and August 2017 with elevated admission BP and who received labetalol, nicardipine or hydralazine monotherapy as initial antihypertensive were analysed. Primary outcomes were systolic and diastolic BP changes from baseline to first BP measurement after initial antihypertensive treatment. Secondary outcomes included haematoma expansion (HE), hospital length of stay (LOS) and modified Rankin Score (mRS) up to 12 months after ICH. Exploratory outcomes assessed effects of race/ethnicity. Linear and logistic regression analyses, adjusted for relevant covariates, were performed to determine associations of antihypertensive class with outcomes. RESULTS: In total, 1156 cases were used in analyses. Antihypertensive class was associated with diastolic BP change (p=0.003), but not systolic BP change (p=0.419). Initial dosing with nicardipine lowered acute diastolic BP than labetalol (least square mean difference (labetalol-nicardipine)=5.47 (2.37, 8.57), p<0.001). Initial antihypertensive class was also found to be associated with LOS (p=0.028), but not with HE (p=0.406), mortality (p=0.118), discharge disposition (p=0.083) or mRS score at discharge, 3, 6 and 12 months follow-up (p=0.262, 0.276, 0.152 and 0.36, respectively). Race/ethnicity variably affected multivariable models. CONCLUSION: In this large acute ICH cohort, initial antihypertensive class was associated with acute diastolic, but not systolic, BP-lowering suggesting differential effects of antihypertensive agents. TRIAL REGISTRATION NUMBER: NCT01202864.

Comparison of efficacy and safety of intracoronary nicardipine and adenosine for fractional flow reserve assessment of coronary stenosis.

BACKGROUND: Administration of intracoronary (IC) adenosine allows an easily feasible, inexpensive, and more rapid alternative method for fractional flow reserve (FFR). It is common practice in many centers worldwide. Nicardipine is a strong coronary vasodilator but its efficacy and safety for assessing FFR is not established. The purpose of present study was to compare the efficacy and safety of IC nicardipine and adenosine for assessing FFR. METHODS: One hundred and fifty-nine patients with a total of 193 vessels undergoing clinically indicated FFR assessment of intermediate coronary stenoses were included. For the initial assessment of FFR, hyperemia was induced by an IC adenosine. After a washout period of 3 min, FFR was reassessed using 200 µg of IC nicardipine. RESULTS: Hyperemic efficacy among two different stimuli was compared. The mean FFR with IC adenosine was 0.83 ± 0.09 and that with an IC nicardipine was 0.84 ± 0.09. The median FFR with an IC adenosine was 0.83 (0.78-0.91) and that with an IC nicardipine was 0.85 (0.79-0.91) (p-value 0.246). Both FFR values showed an excellent correlation (R2 = 0.982, p < 0.001). Nicardipine produced fewer changes in heart rate, less chest pain and less flushing than adenosine. Transient atrioventricular block occurred in 29 patients with IC adenosine and none with IC nicardipine. CONCLUSIONS: IC bolus injection of nicardipine could be introduced as a safe and practical alternative method of inducing hyperemia during FFR measurements. Compared to IC adenosine, IC nicardipine has a similar hyperemic efficacy and excellent side-effect profile.

Clinical efficacy and safety of two concentrations of intravenous nicardipine hydrochloride for nicardipine-related phlebitis in patients with preeclampsia.

To evaluate the effect of two concentrations of intravenous administration of nicardipine hydrochloride on nicardipine-related phlebitis in patients with preeclampsia. A total of 100 preeclampsia patients were administered with nicardipine hydrochloride and divided into the low-concentration (LC) and high-concentration (HC) groups. The incidence and severity of phlebitis, time from treatment to onset of phlebitis, skin temperature, visual analogue scale (VAS) score, induration, and systemic adverse reactions were compared between two groups. The incidence rate of phlebitis in the LC group was 20% (10/50), significantly lower than 42% (21/50) in the HC group (P < 0.05). Ridit Analysis showed that the severity of phlebitis in the LC group was remarkably lower than that in the HC group (P < 0.05). In the LC group, the time from intravenous administration to onset of phlebitis was longer, the average skin temperature was higher, the VAS score was lower, and the indurated area was smaller than those in the HC group (all P < 0.05). Intravenous infusion of nicardipine hydrochloride with constant and low concentration reduces the incidence rate of phlebitis, prolongs the time from treatment to onset of phlebitis, alleviates the severity of phlebitis and pain, maintains skin temperature, and minimizes induration in preeclampsia patients without systemic adverse reactions.

Does intrathecal nicardipine for cerebral vasospasm following subarachnoid hemorrhage correlate with reduced delayed cerebral ischemia? A retrospective propensity score-based analysis.

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.

Comparison of premade clevidipine and pharmacy-prepared nicardipine in time to goal systolic blood pressure in acute cerebrovascular accident.

PURPOSE: To compare pharmacy-prepared nicardipine and premade clevidipine with regard to time to goal systolic blood pressure (SBP) in acute cerebrovascular accident (CVA). METHODS: A retrospective, observational study was conducted comparing patients with acute CVA who received nicardipine or clevidipine. The primary objective was time to goal SBP. Secondary objectives included time from order to administration, time from administration to goal SBP, percentage of SBP readings below goal, total volume administered, hospital and intensive care unit lengths of stay, inpatient mortality and adverse events. RESULTS: Seventy-one patients were included in the study, 37 in the nicardipine group and 34 in the clevidipine group. A significant difference was found in mean time to goal SBP (150.9 minutes in the nicardipine group vs 69.3 minutes in the clevidipine group, P < 0.01). Time from order to administration was 80.1 minutes in the nicardipine group and 35.2 minutes in the clevidipine group (P < 0.01). Mean time from administration to goal SBP was 70.9 minutes in the nicardipine group and 42.3 minutes in the clevidipine group (P = 0.02). There was no difference between groups in percentage of SBP readings below goal, total volume administered, length of stay, or inpatient mortality. Adverse events occurred in 13 (35.1%) of the nicardipine-treated patients and 17 (50%) of the clevidipine-treated patients (P = 0.42). CONCLUSION: Compared to use of pharmacy-prepared nicardipine, use of premade clevidipine was associated with a shorter time to goal SBP in patients with acute CVA. There were no significant between-group differences in safety outcomes. Premade clevidipine should be considered over pharmacy-prepared nicardipine when rapid blood pressure lowering is warranted in acute CVA.

Intensive blood pressure lowering with nicardipine and outcomes after intracerebral hemorrhage: An individual participant data systematic review.

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.

Nicardipine Prolonged Release Implants for Prevention of Delayed Cerebral Ischemia after Aneurysmal Subarachnoid Hemorrhage: A Meta-Analysis.

OBJECTIVES: A paucity of treatments to prevent delayed cerebral ischemia (DCI) has stymied recovery after aneurysmal subarachnoid hemorrhage (aSAH). Nicardipine has long been recognized as a potent cerebrovascular vasodilator with a history off-label use to prevent vasospasm and DCI. Multiple centers have developed nicardipine prolonged release implants (NPRI) that are directly applied during clip ligation to locally deliver nicardipine throughout the vasospasm window. Here we perform a systematic review and meta-analysis to assess whether NPRI confers protection against DCI and improves functional outcomes after aSAH. MATERIALS AND METHODS: A systematic search of PubMed, Ovid Embase, and Cochrane databases was performed for studies reporting the use of NPRI after aSAH published after January 1, 1980. We included all studies assessing the association of NPRI with DCI and or functional outcomes. Findings from studies with control arms were analyzed using a random effects model. A separate network meta-analysis was performed, including controlled NPRI studies, single-arm NPRI reports, and the control-arms of modern aSAH randomized clinical trials as additional comparators. RESULTS: The search identified 214 unique citations. Three studies with 284 patients met criteria for the random effects model. The pooled summary odds ratio for the association of NPRI and DCI was 0.21 (95% CI 0.09-0.49, p = 0.0002) with no difference in functional outcomes (OR 1.80, 95% CI 0.63 - 5.16, p = 0.28). 10 studies of 866 patients met criteria for the network meta-analysis. The pooled summary odds ratio for the association of NPRI and DCI was 0.30 (95% CI 0.13-0.89,p = 0.017) with a trend towards improved functional outcomes (OR 1.68, 0.63 - 4.13 95% CI, p = 0.101). CONCLUSIONS: In these meta-analyses, NPRI decreases the incidence of DCI with a non-significant trend towards improvement in functional outcomes. Randomized trials on the role of intrathecal calcium channel blockers are warranted to evaluate these observations in a prospective manner.

Blood Pressure Control in Acute Stroke: Labetalol or Nicardipine?

PURPOSE: To assess the safety and efficacy of continuous infusion (CIV)-labetalol compared to -nicardipine in controlling blood pressure (BP) in the acute stroke setting. MATERIALS: Patients were eligible if they had a diagnosis of an acute stroke and were administered either CIV-labetalol or CIV-nicardipine. Study outcomes were assessed within the first 24 h of the antihypertensive infusion. RESULTS: A total of 3,093 patients were included with 3,008 patients in the CIV-nicardipine group and 85 in the CIV-labetalol group. No significant difference was observed in percent time at goal BP between the nicardipine (82%) and labetalol (85%) groups (p = 0.351). There was also no difference in BP variability between nicardipine (37%) and labetalol (39%) groups (p = 0.433). Labetalol was found to have a shorter time to goal BP as compared to nicardipine (24 min vs. 40 min; p = 0.021). While CIV-nicardipine did have a higher incidence of tachycardia compared to labetalol (17% vs. 4%; p <0.001), the incidence of hypotension (13% vs. 15%; p = 0.620) and bradycardia (24% vs. 22%; p = 0.797) were similar. CONCLUSIONS: These results indicate that CIV-labetalol and CIV-nicardipine are comparable in safety and efficacy in controlling BP for patients with acute stroke.

Intensive Blood Pressure Lowering in Patients with Moderate to Severe Grade Acute Cerebral Hemorrhage: Post Hoc Analysis of Antihypertensive Treatment of Acute Cerebral Hemorrhage (ATACH)-2 Trial.

OBJECTIVE: To study the effect of intensive blood pressure reduction in patients with moderate to severe intracerebral hemorrhage (ICH) within the subjects recruited in Antihypertensive Treatment of Acute Cerebral Hemorrhage 2 trial. DESIGN: Randomized, multicenter, 2 group, open-label clinical trial. SETTING: A total of 110 sites in the USA, Japan, China, Taiwan, South Korea, and Germany. PATIENTS: A total of 1,000 patients underwent randomization from May 2011 till September 2015. INTERVENTIONS: We analyzed the effect of intensive (goal 110-139 mm Hg) over standard (goal 140-179 mm Hg) systolic blood pressure (SBP) reduction using intravenous nicardipine within 4.5 h of symptom onset in moderate to severe grade subjects with ICH in a non-prespecified analysis. Moderate to severe grade was defined by Glasgow Coma Scale score <13 or baseline National Institutes of Health Stroke Scale score ≥10 or baseline intraparenchymal hemorrhage volume ≥30 mL or presence of intraventricular hemorrhage. The primary outcome was death or disability (score 4-6 on the modified Rankin scale) at 3 months after randomization ascertained by a blinded investigator. MEASUREMENTS AND MAIN RESULTS: Of a total of 682 subjects who met the definition of moderate to severe grade (mean age 61.9 ± 13.1 years, 62.5% men) with a mean baseline SBP of 174.7 ± 24.8 mm Hg, the frequency of hematoma expansion was significantly lower among subjects randomized to intensive SBP reduction than among subjects randomized to standard SBP reduction (20.4 vs. 27.9%, relative risk [RR]: 0.7; 95% confidence interval [CI]: 0.55-0.96). The primary endpoint of death or disability was observed in 52.5% (170/324) of subjects receiving intensive SBP reduction and 48.9% (163/333) of subjects receiving standard SBP reduction (RR: 1.1; 95% CI: 0.9-1.2). CONCLUSIONS: Intensive SBP lowering reduced the frequency of hematoma expansion but did not reduce the rate of death or disability in patients with moderate to severe grade ICH.

Efficacy of low-dose nicardipine for emergent treatment of severe postpartum hypertension in maternal intensive care units: An observational study.

OBJECTIVES: To investigate the efficacy of low-dose intravenous nicardipine for emergent management of severe postpartum hypertension in maternal intensive care units (ICUs). STUDY DESIGN: The initial dosage of nicardipine was dependent upon patient systolic blood pressure (SBP). Patients with an SBP of 160-179 mmHg received an initial dosage of 2 mg/h, and 4 mg/h was administered to patients where SBP exceeded 180 mmHg. MAIN OUTCOME MEASURES: The efficacy of nicardipine was evaluated by measuring the time interval for achieving the target blood pressure, and its safety was determined by the incidence of severe adverse maternal effects. RESULTS: A total number of 101 patients were admitted to the ICU for severe postpartum hypertension and treated with nicardipine. For patients with an SBP of 160-179 mmHg (n = 28), the interval was 14.04 ± 11.00 min (mean ± SD) for achieving the target blood pressure, and the frequency for adjusting the nicardipine dosage was 1.46 ± 1.17. For patients with an SBP ≥ 180 mmHg (n = 73), the interval was 30.75 ± 16.15 min, and the frequency was 1.62 ± 1.38. Three patients with an SBP ≥ 240 mmHg and/or a diastolic blood pressure (DBP) ≥ 130 mmHg failed to achieve the target blood pressure within 60 min. No severe adverse effects occurred in this study. CONCLUSIONS: Our findings showed that low-dose nicardipine could be used to lower elevated blood pressure safely and rapidly in patients admitted to the ICU for severe postpartum hypertension.

Stable Hemodynamics within "No-Touch" Saphenous Vein Graft.

PURPOSE: To investigate the hemodynamics characteristics of the "no-touch" saphenous vein graft (SVG) conduits by nicardipine intraluminal administration in vivo experiment. METHODS: A total of 59 consecutive patients were enrolled and underwent a sequential SVG to three non-left anterior descending (LAD) targets with the average runoff ≤2 mm, 30 with "no-touch" harvest technique (group A) and 29 with conventional preparation (group B). The patients were subject to nicardipine intraluminal injection during off-pump coronary artery bypass grafting (CABG) procedure. The intraoperative flow was measured with the ultrasonic transit time flow meter (TTFM), and the graft patency testified by multi-detector computed tomography (MDCT) angiography, respectively. RESULTS: The baseline blood flow was higher in group A than that in group B (p <0.05). However, the increases in blood flow of SVG conduits in group A were lower than those in group B with 19.7 ± 5.9 vs. 35.4 ± 9.2 mL/min, 14.8 ± 5.6 vs. 23.1 ± 6.8 mL/min, 6.6 ± 2.1 vs. 11.2 ± 4.3 mL/min before the first, second, and third anastomose after nicardipine intraluminal administration, respectively (all p <0.01). CONCLUSIONS: No-touch SVGs were associated with higher baseline blood flow and less rises after nicardipine intraluminal administration during off-pump CABG procedure compared with conventional preparation. The no-touch SVGs seemed to be less spastic and well-tolerated on flow dilatation.

Nicardipine Associated Risk of Short-Term Mortality in Critically Ill Patients with Ischemic Stroke.

BACKGROUND: Hypertensive emergency is commonly associated with acute ischemic stroke and can be a predictor of poor outcome in these patients. Nicardipine and labetalol are commonly administered for the treatment of acute hypertension following stroke. Yet, data are lacking on the safety of these agents in this setting. OBJECTIVE: This study aimed to determine all-cause in-hospital mortality, medication-related hypotensive episodes, development of hospital acquired infections and hospital length of stay between nicardipine and labetalol use for the management of hypertension after acute ischemic stroke. METHODS: This retrospective study used a prospective database of individuals admitted to the neurointensive care unit at a university-based hospital over 39 months. Patients with confirmed ischemic strokes were included in this analysis. Data were recorded for administration of nicardipine and labetalol following acute stroke. RESULTS: A total of 244 patients with acute ischemic stroke were included in this analysis (mean age, 64.3 ± 15 years; 52.2% males). Nicardipine use after acute ischemic stroke was associated with an increased risk of 30-day mortality (odds ratio [OR]: 4.6, 95% confidence interval [CI] 1.3-15.7; P = .02). A single episode of hypotension in the first 72hours of admission was also significantly associated with mortality (OR 4.35 [95% CI 1.2-14.9]; P = .02). CONCLUSIONS: Nicardipine was associated with an increased risk of short-term mortality after acute ischemic stroke. This may have been due to hypotension, tachycardia, or pulmonary edema which were not apparent in our study. Further studies are required to elucidate the cause of this association.

Comparison of Clevidipine and Nicardipine for Acute Blood Pressure Reduction in Patients With Stroke.

OBJECTIVE: The aim of this study was to determine whether clevidipine (CLEV) achieved faster blood pressure control compared to nicardipine (NIC) in patients presenting with either an acute ischemic stroke (AIS) or a spontaneous intracerebral hemorrhage (ICH). METHODS: This was a retrospective, observational, cohort study conducted in patients with AIS or ICH admitted to the emergency department of a Comprehensive Stroke Center from November 2011 to June 2013 who received CLEV or NIC continuous infusion for acute blood pressure management. RESULTS: The study included 210 patients: 70 in the CLEV group and 140 in the NIC group. There was no difference in mean time (standard deviation [SD]) from initiation of the infusion to goal systolic blood pressure (SBP), CLEV: 50 (83) minutes versus NIC: 74 (103) minutes, P = .101. Comparison of the 2 agents within diagnosis showed no difference. Hypotension developed in 5 (7.1%) CLEV patients versus 14 (10%) NIC patients (P = .003). There was no difference in the percentage change at 2 hours; CLEV: -20% (16%) versus NIC: -16% (16%), P = .058. Mean (SD) time to alteplase administration from admission was 56 (22) minutes in the CLEV group versus 59 (25) minutes in the NIC group (P = .684). CONCLUSIONS: There was no difference in the mean time from initiation of the infusion to the SBP goal between agents or in the secondary outcomes. Due to the lack of differences observed, each agent should be considered based on the patient care needs of the institution.

Effectiveness of intrathecal nicardipine on cerebral vasospasm in non-traumatic subarachnoid hemorrhage: a systematic review.

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.

Early Achievement of Blood Pressure Lowering and Hematoma Growth in Acute Intracerebral Hemorrhage: Stroke Acute Management with Urgent Risk-Factor Assessment and Improvement-Intracerebral Hemorrhage Study.

BACKGROUND: Previous studies have revealed that hematoma growth mainly occurs during the first 6 h after the onset of spontaneous intracerebral hemorrhage (ICH). Early lowering of blood pressure (BP) may be beneficial for preventing hematoma growth. However, relationships between timing of BP lowering and hematoma growth in ICH remain unclear. We investigated associations between timing of BP lowering and hematoma growth for ICH. METHODS: The Stroke Acute Management with Urgent Risk-factor Assessment and Improvement (SAMURAI)-ICH Study was a multicenter, prospective, observational study investigating the safety and feasibility of early (within 3 h from onset) reduction of systolic BP (SBP) to < 160 mm Hg with intravenous nicardipine for acute hypertension in cases of spontaneous ICH. The present study was a post hoc analysis of the SAMURAI-ICH study. We examined relationships between time from onset, imaging, and initiation of treatment to target SBP achievement and hematoma growth (absolute growth ≥6 mL) in ICH patients. Target SBP achievement was defined as the time at which SBP first became < 160 mm Hg. RESULTS: Among 211 patients, hematoma growth was seen in 31 patients (14.7%). The time from imaging to target SBP and time from treatment to target SBP were significantly shorter in patients without hematoma growth than in those with (p = 0.043 and p = 0.032 respectively), whereas no significant difference was seen in time from onset to SBP < 160 mm Hg between groups (p = 0.177). Patients in the lower quartiles of time from imaging to target SBP and time from treatment to target SBP showed lower incidences of hematoma growth (p trend = 0.023 and 0.037 respectively). The lowest quartile of time from imaging to target SBP (< 38 min) was negatively associated with hematoma growth on multivariable logistic regression (OR 0.182; 95% CI 0.038-0.867; p = 0.032). CONCLUSIONS: Early achievement of target SBP < 160 mm Hg is associated with a lower risk of hematoma growth in ICH.

Reduction of Nicardipine-Related Phlebitis in Patients with Acute Stroke by Diluting Its Concentration.

BACKGROUND: Nicardipine is frequently used in the treatment of hypertension for patients with acute stroke; however, its dosing is complicated by a high risk of phlebitis. In the present study, we examined whether restricting nicardipine concentration under a specific value could reduce the incidence of nicardipine-related phlebitis in patients with acute stroke. METHODS: Intravenous nicardipine-related phlebitis was retrospectively analyzed. From July 2015, a simple proposition was made to dilute maximum intravenous nicardipine concentration to lower than 130 µg/mL. The maximum intravenous nicardipine concentration and the incidence of phlebitis were compared between patients treated from July 2014 to June 2015 (preproposition group) and patients treated from July 2015 to June 2016 (postproposition group). RESULTS: A total of 300 patients (preproposition group, 138; postproposition group, 162) were included. The postproposition group demonstrated significantly lower maximum intravenous nicardipine concentration (in µg/mL, 76.9, 47.6-104.5 versus 130.4, 69.8-230.8; P < .001) and incidence of phlebitis (9.9%, 16/162 vs. 30%, 42/138; P < .001) than the preproposition group. Multivariable logistic regression analysis revealed that the maximum intravenous nicardipine concentration lower than 130 µg/mL (odds ratio [OR] .15; 95% confidence interval [CI] .06-.35; P < .001) and National Institutes of Health Stroke Scale on admission (OR .95; 95% CI .91-.99; P = .007) were the statistically significant independent factors for phlebitis, which indicated the usefulness of the proposition to dilute maximum intravenous nicardipine concentration to lower than 130 µg/mL. CONCLUSIONS: The simple and appropriate proposition about nicardipine administration lowered maximum nicardipine concentration and reduced the incidence of nicardipine-related phlebitis in patients with acute stroke.