Assessment of Blood Pressure and Heart Rate Related Variables in Acute Stroke Patients Receiving Intravenous Antihypertensive Medication Infusions.

BACKGROUND: We performed an analysis of a large intensive care unit electronic database to provide preliminary estimates of various blood pressure parameters in patients with acute stroke receiving intravenous (IV) antihypertensive medication and determine the relationship with in-hospital outcomes. METHODS: We identified the relationship between pre-treatment and post-treatment systolic blood pressure (SBP) and heart rate (HR)-related variables and in-hospital mortality and acute kidney injury in patients with acute stroke receiving IV clevidipine, nicardipine, or nitroprusside using data provided in the Medical Information Mart for Intensive Care (MIMIC) IV database. RESULTS: A total of 1830 patients were treated with IV clevidipine (n = 64), nicardipine (n = 1623), or nitroprusside (n = 143). The standard deviations [SDs] of pre-treatment SBP (16.3 vs. 13.7, p ≤ 0.001) and post-treatment SBP (15.4 vs. 14.4, p = 0.004) were higher in patients who died compared with those who survived, particularly in patients with intracerebral hemorrhage (ICH). The mean SBP was significantly lower post treatment compared with pre-treatment values for clevidipine (130.7 mm Hg vs. 142.5 mm Hg, p = 0.006), nicardipine (132.8 mm Hg vs. 141.6 mm Hg, p ≤ 0.001), and nitroprusside (126.2 mm Hg vs. 139.6 mm Hg, p ≤ 0.001). There were no differences in mean SDs post treatment compared with pre-treatment values for clevidipine (14.5 vs. 13.5, p = 0.407), nicardipine (14.2 vs. 14.6, p = 0.142), and nitroprusside (14.8 vs. 14.8, p = 0.997). The SDs of pre-treatment and post-treatment SBP were not significantly different in patients with ischemic stroke treated with IV clevidipine, nicardipine, or nitroprusside or for patients with ICH treated with IV clevidipine or nitroprusside. However, patients with ICH treated with IV nicardipine had a significantly higher SD of post-treatment SBP (13.1 vs. 14.2, p = 0.0032). CONCLUSIONS: We found that SBP fluctuations were associated with in-hospital mortality in patients with acute stroke. IV antihypertensive medication reduced SBP but did not reduce SBP fluctuations in this observational study. Our results highlight the need for optimizing therapeutic interventions to reduce SBP fluctuations in patients with acute stroke.

Nicardipine or Nitroprusside for Postoperative Blood Pressure Control in Infants After Surgery for Congenital Heart Disease: Single-Center Retrospective Noninferiority and Cost Analysis, 2016-2020.

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.

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.

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.

Early Initiation of Oral Antihypertensives Reduces Intensive Care Unit Stay and Hospital Cost for Patients with Hypertensive Intracerebral Hemorrhage.

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.

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.

Sodium Nitroprusside as a Hyperinflation Drug and Therapeutic Alternatives.

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.

A New Technique for the Assessment of Cerebral Vasodilatory Capacity as Part of Catheter-Based Cerebral Angiography.

BACKGROUND: Previous studies have demonstrated the value of cerebral vasodilatory capacity assessment for risk stratification in patients with extracranial arterial stenosis or occlusion. We describe a new method that assesses cerebral vasodilatory capacity as part of catheter-based cerebral angiography. METHODS: We assessed regional cerebral blood volume (rCBV) in the arterial distribution of interest using a controlled contrast injection through a diagnostic catheter placed in the common carotid or the subclavian artery. rCBV maps were created using predefined algorithm based on contrast distribution in the venous phase (voxel size 0.466 mm3) into high, intermediate, low, and no detectable rCBV regions. rCBV maps were acquired again after the administration of intra-arterial nicardipine (1.5-2.5 mg), and percentage increases of the area of various grades of rCBV were calculated. RESULTS: Three patients with internal carotid artery stenosis (32% - 64% in severity) and 1 patient with extracranial vertebral artery stenosis (46% in severity) were assessed. There was a variable but consistent increase in the area of high rCBV in the ipsilateral hemisphere in 3 patients with internal carotid artery flow (5.5%-24.5%) and the cerebellum (9.6%) in 1 patient with vertebral artery flow assessments. The increase in high rCBV was most prominent in the patient who received 2.5 mg (24.5%) and least prominent in a patient who received 1.5 mg (5.5%) of intra-arterial nicardipine. There was a concurrent reduction in areas of intermediate and low rCBV (shift) in 3 patients, and there was an increase in all areas of rCBV grades (addition) in 1 patient. CONCLUSIONS: Selective assessment of cerebral vasodilatory response in the affected arterial distribution is feasible during catheter-based cerebral angiography.

Reducing Cost and Intravenous Duration of Nicardipine in Intracerebral Hemorrhage Patients via an Interdisciplinary Approach.

BACKGROUND: The mainstay of acute management of intracerebral hemorrhage (ICH) is blood pressure reduction. Intravenous (IV) nicardipine is an effective but costly intervention for blood pressure reduction in the intensive care unit (ICU). Earlier transition to oral (PO) antihypertensive agents may reduce ICU length of stay (LOS) and associated costs. We sought to study the effectiveness of an interdisciplinary intervention to start earlier transition to PO antihypertensives. METHODS: From July 2011 to July 2012, patients with ICH who received IV nicardipine were reviewed and screened for eligibility by an interdisciplinary team including physicians and pharmacists. These patients were compared to a control group 1 year prior to this intervention. The duration of nicardipine treatment (median hours), estimated costs, and ICU LOS were measured. RESULTS: A total of 35 patients and 44 controls were studied. The median hours of IV nicardipine use were significantly decreased from a baseline mean of 118 to 30 hours (P < .001); total cost savings per year was $433,566 ($18,475 per patient). The average LOS remained similar (8.4 versus 8.9 days, P < .990). In a follow-up study 1 year later, after the intervention was no longer used, a sample of 21 consecutive patients was reviewed and the duration of IV nicardipine treatment had increased to a mean of 96 hours. CONCLUSION: A physician and pharmacist-led project to initiate oral antihyperintensive medications earlier was successful in reducing the duration of IV nicardipine treatment in patients with ICH while leading to substantial cost savings.

An Assessment of the Oral Bioavailability of Three Ca-Channel Blockers Using a Cassette-Microdose Study: A New Strategy for Streamlining Oral Drug Development.

A cassette-microdose (MD) clinical study was performed to demonstrate its usefulness for identifying the most promising compound for oral use. Three Ca-channel blockers (nifedipine, nicardipine, and diltiazem) were chosen as model drugs. In the MD clinical study, a cassette-dose method was employed in which three model drugs were administered simultaneously. Both intravenous (i.v.) and oral (p.o.) administration studies were conducted to calculate the oral bioavailability (BA). For comparison, p.o. studies with therapeutic dose (ThD) levels were also performed. In all studies, blood concentrations of each drug were successfully determined using liquid chromatography-mass spectrometry with the lower limit of quantification of 0.2-2.0 pg/mL. Oral BA of nifedipine in the MD study was approximately 50% and in the same range with that obtained in the ThD study, whereas other two drugs showed significantly lower BA in the MD study, indicating a dose-dependent absorption. In addition, compared with the ThD study, absorption of nicardipine was delayed in the MD study. As a result, nifedipine was considered to be most promising for oral use. In conclusion, a cassette-MD clinical study is of advantage for oral drug development that enables to identify the candidate having desired properties for oral use.

Intravenous nicardipine dosing for blood pressure lowering in acute intracerebral hemorrhage: the Stroke Acute Management with Urgent Risk-factor Assessment and Improvement-Intracerebral Hemorrhage study.

BACKGROUND: Intravenous nicardipine is commonly used to reduce elevated blood pressure in acute intracerebral hemorrhage (ICH). We determined factors associated with nicardipine dosing and the association of dose with clinical outcomes in hyperacute ICH. METHODS: Hyperacute (<3 hours from onset) ICH patients with initial systolic blood pressure (SBP) greater than 180 mm Hg were included. All patients initially received 5 mg/hour of intravenous nicardipine. The dose was adjusted to maintain SBP between 120 and 160 mm Hg. Associations of maximum hourly and total doses with early neurologic deterioration (END), hematoma expansion (>33%), and modified Rankin Scale score 4-6 at 3 months were assessed. RESULTS: Two hundred six patients (81 women, 65.8 ± 11.8 years) were studied. Initial SBP was 201.9 ± 15.9 mm Hg. Maximum and total nicardipine doses were 9.1 ± 4.2 mg/hour and 123.7 ± 100.2 mg/day, respectively. Multivariate analyses revealed that men (standardized regression coefficient [ß] = .20, P = .0030 for maximum dose; ß = .25, P = .0002 for total dose), age (ß = -.28, P = .0002; ß = -.25, P = .0005), and initial SBP (ß = .19, P = .0018; ß = .18, P = .0021) were independently associated with both maximum and total doses. Body weight (ß = .20, P = .0084) was independently associated with total dose. After multivariate adjustment, maximum dose (per 1 mg/hour; odds ratio [OR], 1.25; 95% confidence interval [CI], 1.09-1.45) was independently, and total dose (per 10 mg/day; OR, 1.06; 95% CI, .998-1.132) tended to be independently, associated with END. Nicardipine dose was not associated with hematoma expansion or 3-month outcome. CONCLUSIONS: Nicardipine dose is roughly predictable with sex, age, body weight, and initial SBP in acute ICH. The maximum dose was associated with neurologic deterioration.

A cost analysis of the impact of a new intravenous antihypertensive in managing perioperative blood pressure during cardiac surgery.

OBJECTIVE: To examine the impact of intravenous antihypertensive selection on hospital health resource utilization using data from the Evaluation of CLevidipine In the Perioperative Treatment of Hypertension Assessing Safety Events (ECLIPSE) trials. METHODS: Analysis of ECLIPSE trial data comparing clevidipine to nitroglycerin, sodium nitroprusside, and nicardipine and unit costs based on the Premier Hospital database to assess surgery duration, time to extubation, and length of stay (LOS) with the associated cost. RESULTS: A total of 1414 patients from the ECLIPSE trials and the Premier hospital database were included for analysis. The duration of surgery and postoperative LOS were similar across groups. The time from chest closure to extubation was shorter in patients receiving clevidipine group compared with the pooled comparator group (median 7.0 vs 7.6 hours, P = 0.04). There was shorter intensive care unit (ICU) LOS in the clevidipine group versus the nitroglycerin group (median 27.2 vs 33.0 hours, P = 0.03). A trend toward reduced ICU LOS was also seen in the clevidipine compared with the pooled comparator group (median 32.3 vs 43.5 hours, P = 0.06). The costs for ICU LOS and time to extubation were lower with clevidipine than with the comparators, with median cost savings of $887 and $34, respectively, compared with the pooled comparator group, for a median cost savings of $921 per patient. CONCLUSIONS: Health resource utilization across therapeutic alternatives can be derived from an analysis of standard costs from hospital financial data to matched utilization metrics as part of a randomized controlled trial. In cardiac surgical patients, intravenous antihypertensive selection was associated with a shorter time to extubation in the ICU and a shorter ICU stay compared with pooled comparators, which in turn may decrease total costs.

Systolic blood pressure lowering to 160 mmHg or less using nicardipine in acute intracerebral hemorrhage: a prospective, multicenter, observational study (the Stroke Acute Management with Urgent Risk-factor Assessment and Improvement-Intracerebral Hemorrhage study).

OBJECTIVE: Optimal blood pressure (BP) control in acute intracerebral hemorrhage (ICH) remains controversial. We determined the effects of SBP lowering to 160 mmHg or more using intravenous nicardipine for acute ICH patients. METHODS: This is a prospective, multicenter, observational study conducted in Japan, with the lack of control groups. Patients with supratentorial ICH within 3 h of onset, admission SBP 180 mmHg or more, Glasgow Coma Scale (GCS) 5 or more, and hematoma volume less than 60 ml were initially treated with intravenous nicardipine to maintain SBP between 120 and 160 mmHg with 24-h frequent BP monitoring. The primary endpoints were neurological deterioration within 72 h [GCS decrement ≥ 2 points or National Institutes of Health Stroke Scale (NIHSS) increment ≥ 4 points; estimated 90% confidence interval (CI) on the basis of previous studies: 15.2-25.9%] and serious adverse effects (SAE) to stopping intravenous nicardipine within 24 h (1.8-8.9%). The secondary endpoints included hematoma expansion more than 33% at 24 h (17.1-28.3%), modified Rankin Scale (mRS) 4 or more (54.5-67.9%) and death at 3 months (6.0-13.5%). RESULTS: We enrolled 211 Japanese patients (81 women, 65.6 ± 12.0 years old). At baseline, BP was 201.8 ± 15.7/107.9 ± 15.0 mmHg. Median hematoma volume was 10.2 ml (interquartile range 5.6-19.2), and NIHSS score was 13 (8-17). Neurological deterioration was identified in 17 patients (8.1%), SAE in two (0.9%), hematoma expansion in 36 (17.1%), mRS 4 or more in 87 (41.2%), and death in four (1.9%). All the results were equal to or below the estimated lower 90% CI. CONCLUSION: SBP lowering to 160 mmHg or less using nicardipine appears to be well tolerated and feasible for acute ICH.

Intravenous labetalol compared with intravenous nicardipine in the management of hypertension in critically ill patients.

BACKGROUND: Critically ill patients with acute hypertension often require titratable rapid blood pressure (BP) reductions using parenteral administration of drugs. There are few comparative studies available to make informed drug product selection decisions. The purpose of this study was to evaluate the short-term clinical outcomes and costs of intravenous labetalol or intravenous nicardipine in the management of hypertension in critically ill patients. METHODS: This study was a retrospective analysis of consecutive patients receiving intravenous labetalol or intravenous nicardipine in the intensive care unit with acute elevations in either systolic (>160 mm Hg) or diastolic (>90 mm Hg) BP. Patient demographics, clinical characteristics, and short-term clinical outcomes were abstracted from the medical record. Hospital costs were calculated from hospital billing forms. RESULTS: A total of 189 patients receiving labetalol and 193 patients receiving nicardipine were included in the analysis. The average hourly dose was 37.3 ± 9.4 mg/h for labetalol compared with 7.1 ± 5.6 mg/h for nicardipine (P < .001). The average total dose of labetalol was 170.9 ± 32.6 mg compared with 112.2 ± 29.1 mg for nicardipine (P = .02). The duration of therapy was significantly shorter for labetalol (8.2 ± 6.2 hours) compared with nicardipine (15.8 ± 4.4 hours) (P = .03). There were a greater number of dose titrations with labetalol (6.1 ± 6.2) than with nicardipine (4.7 ± 4.9), but this difference was not significantly different (P = .29). There were no significant differences in the magnitude of the average change in systolic (P = .79) or diastolic (P = .82) BP between labetalol and nicardipine. The proportion of patients achieving their BP targets was significantly greater with nicardipine (83%) than with labetalol (67%) (P = .04). The proportion of patients requiring an alternate antihypertensive agent was significantly greater with labetalol than with nicardipine (31% vs 17%; P = .02). The total number of all-cause adverse events was significantly greater with labetalol (61%) than with nicardipine (48%) (P = .04). Labetalol was associated with a significantly greater incidence of hypotension and bradycardia or atrioventricular block compared with nicardipine. There was no significant difference in the frequency of other adverse events between these 2 drugs. The median hospital costs were not significantly different between patients receiving labetalol and patients receiving nicardipine. CONCLUSION: Our study suggests that nicardipine is a more effective antihypertensive agent than labetalol in an unselected group of patients who develop hypertension in the intensive care unit setting. A major advantage of nicardipine compared with labetalol was fewer adverse effects. Nicardipine was associated with less hypotension and bradycardia or atrioventricular block, resulting in a lower rate of drug discontinuation compared with labetalol.

Intraventricular nicardipine for aneurysmal subarachnoid hemorrhage related vasospasm: assessment of 90 days outcome.

BACKGROUND: Delayed cerebral arterial vasospasm is one of the leading causes of death and disability after aneurysmal subarachnoid hemorrhage (aSAH). We evaluated the safety of intraventricular nicardipine (IVN) for vasospasm (VSP) in aSAH patients, and outcomes compared with a control population. METHODS: A retrospective case-control study was conducted for aSAH patients treated with IVN at Mayo Clinic, Jacksonville, FL, from March 2009 to January 2011. Controls were matched by age, gender, and Fisher grade. Safety was evaluated by the incidence of intracranial bleeding and infection. Outcome was measured by Glasgow Outcome Scale at 30 and 90 days. IVN effects on VSP were evaluated by transcranial Doppler (TCD). RESULTS: Thirteen aSAH patients and one arteriovenous malformation (AVM)-related SAH patient received IVN for VSP and were matched with 14 aSAH patients without IVN therapy for a total of 28 cases. Median dose was 4 mg (range 3-7), and median number of doses was seven (range 1-17). Mean flow velocity decreased after IVN (120.2 and 101.6 cm/s-82.0 and 72.8 cm/s, right and left middle cerebral arteries, respectively). No significant difference was seen in clinical outcomes between controls and cases at 30 days (P = 0.443) and 90 days (P = 0.153). There were no incidences of bleeding or infection with 111 nicardipine injections. CONCLUSIONS: IVN appears relatively safe and effective in treating VSP by TCD, but there was no difference in clinical outcomes between nicardipine and control patients at 30 and 90 days. In the future, larger studies are needed to evaluate the clinical outcome with IVN.

A multicenter comparison of outcomes associated with intravenous nitroprusside and nicardipine treatment among patients with intracerebral hemorrhage.

INTRODUCTION: No clinical data exist to compare outcomes between patients with intracerebral hemorrhage (ICH) treated with different intravenous antihypertensive agents. This study was performed to compare outcomes among patients with ICH who were treated with intravenous infusion of different antihypertensive medications during the first 24 hours after admission. METHODS: We analyzed one-year data (2005-2006) from the Premier database which is a nationally representative hospital discharge database containing data pertaining to admissions in the United States. We compared discharge outcomes, length of stay, and cost of hospitalization between groups of patients who were treated using either intravenous nicardipine or nitroprusside infusion. Chi-square and ANOVA were used for univariate analysis. Logistic and linear regression analyses were performed to adjust for baseline risk of mortality between the two groups. RESULTS: A total of 12,767 admissions with primary diagnosis of ICH were identified. Nicardipine was administered in 926 patients (7.3%) and nitroprusside was administered in 530 (4.3%) patients. There was no difference in baseline disease severity or risk of mortality among patients who were administered nicardipine or nitroprusside. After adjustment for baseline risk of mortality, the risk of in-hospital mortality (odds ratio [OR] 1.7, 95% confidence interval [95% CI] 1.3-2.2) was higher among patients treated with nitroprusside compared with nicardipine. The risk of in-hospital mortality was also higher after adjustment for baseline risk of mortality and hospital characteristics in patients treated with nitroprusside (OR 1.6, 95% CI 1.2-2.1). After exclusion of patients who died during hospitalization, there was no difference in length of stay and total hospital cost in the multivariate analysis. CONCLUSION: Use of nicardipine compared with nitroprusside infusion during the first 24 h after ICH may be associated with reduced risk of in-hospital mortality without any increase in the hospitalization cost or length of stay.

Assessment of the effects of L- and N-type Ca2+ channel blocking drugs using canine blood-perfused papillary muscle preparations.

It is important to accurately and conveniently assess the effects of L- and N-type Ca(2+) channel blocking drugs, which are commonly used for treatment of hypertension, but no method is available to simultaneously assess the effects of them in the same preparation. We have therefore designed an ex vivo method to measure the changes in contractile response of anterior papillary muscle of right ventricle and myocardial interstitial norepinephrine (NE) level using canine blood-perfused papillary muscle preparations. Papillary muscle-developed tension (PMDT) induced by an electronic stimulator was measured with force transducer. Myocardial interstitial NE effluent was collected by microdialysis fiber, which was implanted at the base of the papillary muscle, and measured with high performance liquid chromatography. Cilnidipine, a typical L- and N-type Ca(2+) channel blocker, was used to prove the efficiency of this method. First, to assess the effects of drugs on L-type Ca(2+) channel, the changes in basal PMDT were measured. Cilnidipine and nicardipine, a selective L-type Ca(2+) channel blocker, but not omega-conotoxin GVIA (omega-CTX), a selective N-type Ca(2+) channel blocking peptide, decreased basal PMDT dose-dependently. Second, to assess the effects of drugs on N-type Ca(2+) channel, the changes in PMDT and myocardial interstitial NE level by intracardiac sympathetic ganglion stimulation were measured. Cilnidipine and omega-CTX, but not nicardipine, dose-dependently reduced sympathomimetic increases in PMDT and myocardial interstitial NE level. These results indicate that our method is efficient to assess the effects of various L- and N-type Ca(2+) channel blocking drugs in the same papillary muscle preparation.

"Pharmacologic" distal protection using prophylactic, intragraft nicardipine to prevent no-reflow and non-Q-wave myocardial infarction during elective saphenous vein graft intervention.

BACKGROUND: Coronary saphenous vein bypass graft (SVG) stenting has been associated with up to a 30% rate of no-reflow or myocardial infarction (MI) when performed without distal protection. METHODS: We evaluated the technique using prophylactic pharmacologic arteriolar vasodilatation with intracoronary nicardipine followed by immediate direct stenting for the treatment of degenerated coronary SVGs without mechanical distal protection. Data were collected from 83 consecutive elective SVG interventions in 68 patients. Quantitative coronary angiographic measurements were performed by the Borgess angiographic core lab. Electrocardiograms (ECGs), CPKs, and CPK-MBs were obtained preprocedure and at 12 to 18 hours after the intervention. Follow-up data at 30 days were obtained in 67/68 (98%) patients. RESULTS: The average graft age was 11.9 +/- 6.6 years with thrombus in 26/83 vessels (31%). The primary adverse endpoint of total CPK >3 times the upper limit of normal (ULN), or CPK-MB >3 times the ULN were seen in 1/68 (1.5%) and 3/68 (4.4%) patients, respectively. No-/slow-reflow was observed transiently in 2/83 SVG interventions (2.4%). Of the patients, 1/68 had persistent, minor ECG changes after stenting (1.4%). No patient had a Q-wave MI. Inhospital major adverse cardiac events (MACE) (death, MI, repeat TLR) were observed in only 3/68 patients (CPK-MB elevation). There were no additional MACE events (0/68) from hospital discharge to 30 days. CONCLUSIONS: (1) Prophylactic vasodilatation with intragraft nicardipine followed by direct stenting appears to be a safe and effective means of performing elective SVG revascularization; (2) this approach may provide a simple and time- and cost-effective alternative or adjunct to mechanical distal protection for elective SVG interventions.

Pharmacologically stimulated portal flow measurement by magnetic resonance imaging for assessment of liver function.

PURPOSE: To evaluate pharmacologically stimulated portal flow measured by magnetic resonance (MR) imaging for assessment of liver function. MATERIALS AND METHODS: Pharmacologically stimulated portal flow was measured by phase contrast MR imaging in 27 patients when they were undergoing abdominal angiography for liver tumors or gall bladder cancer. The patients included 11 cases of liver cirrhosis and eight of chronic hepatitis. Pharmacological stimulation was done by infusion of 10 microg/Kg of nicardipine hydrochloride into the superior mesenteric artery through an angiographic catheter. We examined the correlation between stimulated or non-stimulated portal flow and biochemical liver function tests. RESULTS: Correlation coefficients and their corresponding p values between non-stimulated portal flow and the indocyanine green residual rate at 15 min after injection (ICG R15), serum albumin (ALB), total bilirubin (TB), cholinesterase (CHE), and hepaplastin test (HP) were--0.414 (0.056), 0.296 (0.134), -0.570 (0.002), 0.289 (0.153), and 0.321 (0.126), respectively, whereas those between stimulated portal flow and ICG R15, ALB, TB, CHE, and HP were--0.561 (0.007), 0.411 (0.033), -0.509 (0.007), 0.445 (0.023), and 0.494 (0.014), respectively. CONCLUSION: Stimulated portal flow showed better correlations with biochemical liver function tests than non-stimulated portal flow. It is suggested that stimulated portal flow measurement is more useful for the evaluation of liver function than non-stimulated portal flow measurement.