Intravenous Infusion Of Nicardipine Research Articles

Utility of nicardipine in the management of hypertensive crises in adults with reduced ejection fractions

BackgroundNicardipine 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). MethodsThis 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. ResultsOf 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. ConclusionIn 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.

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

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). 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 24h versus after 24h 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. 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 ± 141.3h, p <0.005), nicardipine cost ($14,207 vs $29,299, p < 0.01), ICU LOS (2 vs 5days, 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. Early initiation of oral antihypertensives is safe and may have a significant financial impact on patients with hypertensive ICH.

Abstract TP329: Early Initiation of Oral Antihypertensives Reduces Intensive Care Unit Stay and Hospital Cost in Patients With Hypertensive Intracerebral Hemorrhage

Background and Purpose: Intravenous nicardipine infusion is effective for intensive blood pressure (BP) control in patients with hypertensive intracerebral hemorrhage (ICH). However, its use requires close hemodynamic monitoring in the intensive care unit (ICU). Prompt transition from nicardipine infusion to oral antihypertensives may reduce ICU length of stay (LOS). This study aimed to examine the effect of early verse late initiation of oral antihypertensives on hospital resource utilization in patients with hypertensive ICH. Methods: This is a retrospective study of patients with hypertensive ICH and initial systolic BP ≥ 180 mmHg from January 1, 2013 to December 31, 2017. Only patients who received nicardipine infusion were included. Based on timing of receiving oral antihypertensives within or after 24 hours of emergency department arrival, patients were divided into study or control group, respectively. Baseline characteristics, duration of nicardipine infusion, ICU and hospital LOS, functional outcome at hospital discharge, and the cost were compared between the 2 groups using univariate and multivariate analysis to adjust for dependent variables. Results: A total of 166 patients (90 in study group, 76 in control group) were identified. There was no significant difference in demographic features, past medical history or initial SBP between the 2 groups. Patients in study group had lower initial NIHSS and ICH scores but higher GCS score than those in the control group. Using multivariant regression analysisto adjust for initial SBP, NIHSS, GCS and ICH scores, early initiation of oral antihypertensives was associated with significant shorter ICU LOS (median 2 vs 5, p =0.004), decreased duration of nicardipine infusion (55.5 ±60.1 vs 121.6 ±141.3, P =0.002), less pharmaceutical cost (median $14207 vs $ 29299, p =0.007) and total hospital cost (median $ 24564 vs $ 47366, p =0.007). After adjustment of confounders, there was also no significant difference in functional independence (mRS 0-2, 42.2% vs 17.1%, p =0.112) or mortality (6.7% vs 13.2%, p = 0.789) between the 2 groups. Conclusions: Early initiation of oral antihypertensive therapy is associated with reduced resource utilization and hospital cost in patients with hypertensive ICH.

Effect of stellate ganglion block versus intraluminal application of verapamil-nitroglycerine solution on internal mammary artery graft blood flow rate in patients undergoing on-pump coronary artery bypass grafting

Background Left internal mammary artery (IMA) graft is the most promising arterial conduit for coronary artery bypass grafting. Stellate ganglion block (SGB) induces sympathetic blockade and is used to prevent or control spasm of the internal mammary artery. The purpose of this study was to investigate the effect of left SGB on left IMA blood flow rate. Patients and methods A total of 170 patients aged between 65 and 70 years, with American Association of Anesthesiologists physical status II and III, and scheduled for elective coronary artery bypass grafting, were randomly allocated to either a SGB group or a verapamil-nitroglycerine group. In the SGB group, the patients received SGB using 8 ml of bupivacaine 0.25%. In the verapamil-nitroglycerine group, the patients received intraluminal injection of the harvested IMA graft with a solution, containing verapamil 5 mg, nitroglycerine 2.5 mg, heparin 500 U, 8.4% NAHCO3 0.2 ml, and ringer solution 40 ml, throughout its whole length using a small syringe, and with a low dose of intravenous nicardipine infusion started after harvesting (5 mg nicardipine in 100 ml saline at a rate of 0.5 mg or 10 ml/h). IMA blood flow rate (primary outcome), abnormal ECG changes, ICU length of stay, intra-aortic balloon usage, pre–postoperative pulse rate and blood pressure, incidence of atrial fibrillation, radio-femoral arterial pressure difference, pre–postoperative ejection fraction, need for re-exploration, and mortality rate were observed. Results This prospective study showed a significant increase of IMA blood flow rate (P Conclusion The results of this study showed that SGB prevents IMA spasm, increases its blood flow rate, and decreases incidence of atrial fibrillations compared with intraluminal injection of verapamil and nitroglycerine combined with intravenous nicardipine.

A rare presentation of clinically intractable hypertension: Pancreatic paraganglioma

Summary Paraganglioma is a rare extra-adrenal pheochromocytoma which originates from chromaffin cells within the ganglia of the sympathetic trunk and of the celiac, renal, suprarenal, and hypogastric plexuses. Pancreatic paragangliomas are rarer still. And even then, paragangliomas are mostly reported to be nonfunctional. We report a case of a 64-year-old woman with underlying disease of hypertension who presented with biliary colic. Contrast-enhanced computer tomography showed an enhancing mass in the uncinate process of the pancreas. Pylorus-sparing Whipple procedure was performed for complete tumor excision. Hypertensive crisis developed after Whipple, which improved after continuous intravenous nicardipine infusion. Pathology revealed a paraganglioma. A 24-h catecholamine urine test showed increased norepinephrine and vanillylmandelic acid level. Functional paraganglioma was diagnosed.

Transient rebound hypertension after termination of intravenous nicardipine infusion in cesarean section patients with gestational hypertension and preeclampsia

Transient rebound hypertension after termination of intravenous nicardipine infusion in cesarean section patients with gestational hypertension and preeclampsia

Hemispheric differences in blood pressures of patients with putaminal and thalamic hemorrhages

Our assumption that blood pressure (BP) in supratentorial hypertensive intracerebral hemorrhage patients does not differ significantly according to the hemispheric laterality has never been verified before. This study was carried out to explore the possibility of hemispheric BP differences and whether this might influence the outcomes. A review of the charts/radiographic images of 281 patients with putaminal/thalamic hemorrhages diagnosed within 6 h of symptom onset was performed. Immediately after arrival, they received a continuous intravenous nicardipine infusion to lower and maintain systolic BP (SBP) between 120 and 160 mmHg. They were quadrichotomized as follows: left putamen (LP, n=89), right putamen (RP, n=69), left thalamus (LT, n=68), and right thalamus (RT, n=55). Two-group or four-group comparisons were made on demographic variables, BPs, and outcomes. Patients with left-sided hemorrhages presented with significantly worse neurologic scores in both hemorrhage categories and tended to sustain larger hematomas than their right-sided counterparts. Significant differences in SBPs between LP and RP (205 ± 31 vs. 189 ± 29 mmHg, P<0.01) as well as in diastolic BPs between LT and RT (109 ± 19 vs. 97 ± 20 mmHg, P=0.03) were noted. Multivariate regression analysis showed that patients with SBPs of at least 220 mmHg were 2.9 times more likely to harbor left-sided hemorrhages. There were no significant intergroup differences in responsiveness to a continuous intravenous nicardipine infusion or 30-day mortality rates. Although the differences in BPs are unlikely to have influenced outcomes, future trials involving supratentorial hypertensive intracerebral hemorrhages may benefit from considering hemispheric differences in BP and other demographic variables.

わが国におけるAntihypertensive Treatment of Acute Cerebral Hemorrhage（ATACH）-II試験の開始：デザインと国内研究体制の構築

The Antihypertensive Treatment for Acute Cerebral Hemorrhage (ATACH)-II Trial (ClinicalTrials.gov no. NCT01176565; (UMIN 000006526) is an international, multicenter, randomized, concurrently-controlled, parallel arm, Phase III trial to determine the therapeutic benefit of early intensive systolic blood pressure (SBP) lowering compared with standard SBP lowering for acute hypertension in patients with spontaneous intracerebral hemorrhage (ICH). The Trial is funded by the National Institutes of Health in the United States and led by Dr. Adnan Qureshi at the University of Minnesota. Seventeen Japanese institutions will participate in this Trial. This article describes the latest version of the study design and our endeavors to develop the Japanese research network for stroke clinical research. The ATACH-II Trial plans to randomize a maximum of 1,280 (approximately 400 from Japan) subjects who have supratentorial ICH (hematoma volume <60cc) with Glasgow Coma Scale ≥5 and SBP of >180mmHg. Subjects undergo a follow-up assessment for functional and quality of life assessment at 90 days post-randomization. The primary research hypothesis of the trial is that intensive SBP reduction (to ≤140mmHg) using intravenous nicardipine infusion for 24 hours post-randomization reduces the proportion of death and disability at 90 days by ≥10% (absolute) compared to the standard SBP reduction (to 140-180mmHg range) among subjects with ICH whose treatment is initiated within 4.5 hours of symptom onset. The ATACH-II Trial could be the seminal research project for stroke researchers in Japan to demonstrate themselves as effective contributing members of investigator-initiated international clinical trials.

Autoregulation after ischaemic stroke

Absent outcome data from randomized clinical trials, management of hypertension in acute ischaemic stroke remains controversial. Data from human participants have failed to resolve the question whether cerebral blood flow (CBF) in the peri-infarct region will decrease due to impaired autoregulation when systemic mean arterial pressure (MAP) is rapidly reduced. Nine participants, 1-11 days after hemispheric ischaemic stroke, with systolic blood pressure more than 145 mmHg, underwent baseline PET measurements of regional CBF. Intravenous nicardipine infusion was then used to rapidly reduce mean arterial pressure 16 +/- 7 mmHg and CBF measurement was repeated. Compared with the contralateral hemisphere, there were no significant differences in the percent change in CBF in the infarct (P = 0.43), peri-infarct region (P = 1.00) or remainder of the ipsilateral hemisphere (P = 0.50). Two participants showed CBF reductions of greater than 19% in both hemispheres. In this study, selective regional impairment of CBF autoregulation in the infarcted hemisphere to reduced systemic blood pressure was not a characteristic of acute cerebral infarction. Reductions in CBF did occur in some individuals, but it was bihemispheric phenomenon that likely was due to an upward shift of the autoregulatory curve as a consequence of chronic hypertension. These results indicate individual monitoring of changes in global CBF, such as with bedside transcranial Doppler, may be useful to determine individual safe limits when MAP is lowered in the setting of acute ischaemic stroke. The benefit of such an approach can only be demonstrated by clinical trials demonstrating improved patient outcome.

Management of Blood Pressure for Acute and Recurrent Stroke

Marc Fisher MD Kennedy Lees MD Section Editors: Hypertension is the most important modifiable risk factor for stroke.1,2 It is estimated that 25% or more of strokes may be attributable to hypertension. Because many patients with stroke have mild hypertension or prehypertension, we have shifted our focus and now think of stroke on a continuum of risk based on blood pressure (BP) level rather than on a threshold effect.3 Because high BP may not exist in isolation, a wider definition of hypertension has been proposed that also takes into account the absolute risk of cardiovascular events and associated metabolic factors or early disease markers.3 Lowering BP reduces the risk of stroke. Epidemiological studies have shown that for each 10 mm Hg lower systolic blood pressure (SBP), there is a decrease in risk of stroke of approximately one third in persons aged 60 to 79 years. This association is continuous down to levels of at least 115/75 mm Hg and is consistent across sexes, regions, stroke subtypes, and for fatal and nonfatal events.4 Lowering diastolic blood pressure (DBP) was once the main target to achieve stroke and other cardiovascular event reduction, but SBP has now become the target.3 As recently shown, even the elderly with sustained SBP elevation may gain from BP reduction in relation to less fatal or nonfatal stroke, death, and heart failure.5 Although the role of longer-term BP control to improve outcomes in patients with stroke is undisputed, BP management immediately after a stroke remains controversial. In an effort to resolve this controversy, several pilot clinical trials have been initiated. In this review, we discuss the results of some of these trials and available evidence-based guidelines for BP control in the settings of acute ischemic and hemorrhagic stroke (excluding subarachnoid hemorrhage) and …

Antihypertensive Treatment of Acute Cerebral Hemorrhage (ATACH): Rationale and Design

This trial is a multicenter open-labeled pilot trial to determine the tolerability and safety of three escalating levels of antihypertensive treatment goals for acute hypertension in 60 subjects with supratentorial intracerebral hemorrhage (ICH). The pilot trial is the natural development of numerous case series evaluating the effect of antihypertensive treatment of acute hypertension in subjects with ICH. The proposed trial will have important public health implications by providing necessary information for a definitive phase III study regarding the efficacy of antihypertensive treatment of acute hypertension in subjects with ICH. The specific aims of the present pilot study are to: (1) Determine the tolerability of the treatment as assessed by achieving and maintaining three different systolic blood pressure goals with intravenous nicardipine infusion for 18 to 24 hours postictus in subjects with ICH who present within 6 hours of symptom onset; (2) Define the safety, assessed by the rate of neurological deterioration during treatment and serious adverse events, of three escalating systolic blood pressure treatment goals using intravenous nicardipine infusion; and (3) Obtain preliminary estimates of the treatment effect using the rate of hematoma expansion (within 24 hours) and modified Rankin scale and Barthel index at 3 months following symptom onset.

Treatment of acute hypertension in patients with intracerebral hemorrhage using American Heart Association guidelines*

To determine the feasibility and safety of treatment of acute hypertension in patients with intracerebral hemorrhage within 24 hrs of symptom onset. Elevated blood pressure, observed in up to 56% of patients with intracerebral hemorrhage, may predispose to hematoma expansion; on the other hand, reduction of blood pressure may reduce hematoma expansion and subsequent death and disability. Single-center prospective registry supplemented by retrospective chart review. University-affiliated medical center with dedicated stroke service. All patients admitted to the stroke service with spontaneous intracerebral hemorrhage and acute hypertension within 24 hrs of symptom onset. Patients were treated with intravenous nicardipine within 24 hrs of symptom onset to reduce and maintain mean arterial pressure of <130 mm Hg. The mean arterial pressure goal was consistent with the American Heart Association guidelines. The primary outcome was the tolerability of the treatment as assessed by achieving and maintaining the mean arterial pressure goals for 24 hrs after initiation of intravenous nicardipine infusion. Other end points ascertained were: neurologic deterioration defined by a decline in Glasgow Coma Scale from pretreatment assessment by >or=2 points or increase in National Institutes of Health Stroke Scale score by >or=2 points and hemorrhage growth defined as an increase in the volume of intraparenchymal hemorrhage of >33% as measured by image analysis on the 24-hr computed tomographic scan compared with the baseline computed tomographic scan. Rates of favorable outcome and death were ascertained at 1 month. Of the total 46 patients admitted with intracerebral hemorrhage in our service, 29 patients were treated. Mean age of the treated patients was 58 +/- 13 yrs; ten were women. Initial National Institutes of Health Stroke Scale ranged from 1 to 38. The primary outcome of tolerability was achieved in 25 of the 29 patients (86%). Neurologic deterioration was observed in 4 of 29 patients. Hematoma enlargement was observed in five patients. Favorable outcome (defined as modified Rankin scale of <or=2) and death at 1-month was observed in 11 (38%) and 9 (31%) of the 29 patients, respectively. We observed a high rate of tolerability among patients with intracerebral hemorrhage who were treated with intravenous nicardipine using mean arterial pressure goals defined by American Heart Association guidelines within 24 hrs of symptom onset.

A Review of Calcium Channel Antagonists in the Treatment of Pediatric Hypertension

All children aged > or = 3 years should have an annual blood pressure (BP) measurement taken during a routine physical examination. Physicians should become familiar with recommended pediatric normative BP tables. BP above the 95th percentile may require drug therapy. There are several categories of antihypertensives available to the clinician. Calcium channel antagonists (CCAs) are a class of drugs that exert their antihypertensive effect by inhibiting the influx of calcium ions across the cell membranes. This results in dilatation of peripheral arterioles. When given orally, CCAs are metabolised in the liver by cytochrome P450 (CYP) enzyme CYP3A4; hence, some CCAs will affect the half-life of drugs that share this enzyme system for their metabolism. CCAs can be safely used in children with renal insufficiency or failure and as a general rule there is no need to modify drug dosage in this population. CCAs are generally well tolerated; most adverse effects appear to be dose related. Headache, flushing, gastrointestinal upset, and edema of the lower extremities are the most common symptoms reported with the use of CCAs. Pediatric data regarding safety and efficacy of CCAs have mostly been obtained from retrospective analyses. Extended-release nifedipine and amlodipine are the two most commonly used oral CCAs in the management of pediatric hypertension. These drugs can be given once a day, although many children require twice-daily administration. Extended-release nifedipine has to be swallowed whole; hence, its use in younger children who cannot swallow pills is limited. Amlodipine can be made into a solution without compromising its long duration of action; therefore, it is the CCA of choice for very young children. Oral short-acting nifedipine and intravenous nicardipine are safe and effective CCAs for the management of hypertensive crisis in children. Short-acting nifedipine can cause unpredictable changes in BP; hence, it should be used cautiously and in low doses. Intravenous nicardipine has a rapid onset of action and a short half-life. Intravenous infusion of nicardipine can be titrated for effective control of BP. Intravenous nicardipine has been used safely in hospitalized children and newborns for the management of hypertensive crisis, and for controlled hypotension during surgery. CCAs are a class of antihypertensives that are safe and effective in pediatric patients. They have relatively few adverse effects and are well tolerated by children. This article reviews CCAs as antihypertensives in the management of pediatric hypertension.

Recovery from renal failure in malignant hypertension associated with primary aldosteronism: effect of an ACE inhibitor

Sir, Primary aldosteronism is one of the most common causes of secondary hypertension. However, it is rare for this disease to induce malignant hypertension associated with vascular organ damage including renal failure.1 One of the reasons for this is that, even in the malignant phase, renin activity and subsequent angiotensin II production remain suppressed in primary aldosteronism. Here, we report a case with aldosterone‐producing adenoma and increased renin activity complicated by malignant hypertension and renal failure, which required haemodialysis therapy. This case is noteworthy, because medical therapy with angiotensin‐converting enzyme (ACE) inhibitor effectively improved renal function, allowing discontinuation of dialysis. A 40‐year‐old woman consulted a physician on 2 January 2000, complaining of dyspnea, general fatigue, anorexia and headache. The patient appeared drowsy and her blood pressure was 260/140 mmHg. Serum creatinine was 7.1 mg/dl and severe pleural effusion was detected on chest X‐ray. Optic fundi exhibited papilloedema and haemorrhage (Keith‐Wagener's grade IV). She was admitted to hospital and treated with antihypertensive drugs and intermittent haemodialysis, which was needed three times a week thereafter. Blood pressure was managed by continuous intravenous infusion of nicardipine, which effectively lowered blood pressure to 170/80 mmHg. As renal function had not improved, the patient was transferred to our hospital …

Effect of nicardipine on vascular capacitance: Comparison with sodium nitroprusside during induced hypotension

The purpose of this study was to examine the effects of nicardipine and sodium nitroprusside (SNP) on vascular capacitance in the rat. In ten rats anesthetized with pentobarbital, mean arterial pressure was lowered to about 70 mmHg and subsequently 50 mmHg by intravenous infusion of nicardipine or SNP. Vascular capacitance was assessed before and during nicardipine- or SNP-induced hypotension by measuring the mean circulatory filling pressure (MCFP). MCFP was measured during a brief period of circulatory arrest produced by inflating a balloon inserted in the right atrium. MCFP was significantly decreased by SNP from 7.1 ±0.3 mmHg at control to 5.6 ± 0.4 mmHg and 4.4 ± 0.3 mmHg at mean arterial pressures of 70 mmHg and 50 mmHg, respectively. However, MCFP stayed at a similar level to that of the control during nicardipine-induced hypotension. These results suggest that nicardipine has a negligible influence on vascular capacitance during induced hypotension, whereas SNP has a potent vasodilating effect on the venous system as well as the arterial system.

Effects of nicardipine, nitroglycerin, and nitroprusside on left ventricular diastolic function during enflurane anesthesia

The purpose of this study was to evaluate the effects of nicardipine (NCR), nitroglycerin (NTG), or nitroprusside (SNP) on left ventricular diastolic function during enflurane anesthesia in acutely instrumented dogs. Using echocardiography, time constants for the decline in isovolumic left ventricular pressure (T), stiffness constant (K), diastolic time intervals, and left ventricular filling rates were measured in 21 mongrel dogs during the following conditions: (1) 0% enflurane (control), (2) 3.3% enflurane, (3) intravenous infusion of NCR, 1 μg/kg/min, NTG, 2 μg/kg/min, or SNP, 2 μg/kg/min, during 3.3% enflurane, and (4) intravenous infusion of NCR, 2 μg/kg/min, NTG, 4 μg/kg/min, or SNP, 4 μg/kg/min, during 3.3% enflurane. During 3.3% enflurane anesthesia, T and K increased significantly, and left ventricular filling rates decreased. The administration of NCR, NTG, or SNP returned T and K to control levels. Left ventricular rapid filling rate returned toward the control level only with NCR ( P < 0.05, NCR v NTG, SNP). It is concluded that the depression of diastolic function during enflurane anesthesia was improved by NCR or other vasodilators. The extent and mechanism of action of these vasodilators might differ, however.

Early treatment of ischemic stroke with a calcium antagonist.

We performed a feasibility and safety study (phase II) of nicardipine, a calcium antagonist, in 57 patients. The objectives of the study were to begin therapy as early as possible (less than or equal to 12 hours) after the onset of ischemic stroke and to administer as high a dose as possible. All patients received an intravenous infusion of nicardipine for 72 hours, starting with a dose of 3 mg/hr and increasing to a maximum dose of 7 mg/hr. Upward titration of the dose was limited by a 10% decrease in blood pressure or a 20 beats/min increase in pulse. Intravenous therapy was followed by 30 days of oral therapy. The mean +/- SD interval from onset of stroke to commencement of therapy was 9.1 +/- 5.4 hours. Adverse reactions consisted primarily of hypotension requiring discontinuation of therapy in four patients. Score on a graded neurologic examination increased from 41/100 at baseline to 64/100 at 3 months for the 41 patients completing follow-up. There was no correlation between the dose of nicardipine administered and outcome, but the 11 patients starting therapy less than or equal to 6 hours after onset did better than those starting therapy 6-12 hours after onset. Further study of very early therapy with nicardipine is justified.

脳動脈瘤破裂後の脳血管攣縮に対する Nicardipine 大量持続静注の効果

Effect of high doses of nicardipine on cerebral vasospasm was studied in patients with ruptured aneurysms. Twenty patients were treated with nicardipine (Group A), whereas 21 patients did not receive the drug (Group B). Intravenous infusion of nicardipine started within 24 hours after subarachnoid hemorrhage (SAH) in 18 cases, and on Day 4 and Day 5 in 2 cases, respectively. The dosage was 3mg/hr in 3 cases, 5mg/hr in 4, 7mg/hr in 7, and 10mg/hr in 6, for 9 to 21 days. Early surgery was performed within 72 hours after SAH in 15 cases in Group A and 16 cases in Group B, and other cases in both groups had delayed operation. Postoperative angiography was carried out 8 to 16 days after SAH in 15 cases in Group A and 16 cases in Group B. The flow velocity in middle cerebral artery was recorded with transcranial Doppler sonography every other day in 18 cases in Group A and all cases in Group B.No patients in Group A demonstrated ischemic symptoms and low-density areas on CT scans, while high incidences of brain ischemia (48%) and low-density areas on CT scans (43%) were noted in Group B patients. Severe angiographic vasospasm was shown in 7 of 16 patients in Group B, but was not found in any patients in Group A. Statistically significant increase in mean blood flow velocity in the M1 segment was noted by transcranial Doppler sonography on Day 6, Day 8, and Day 10 in Group B.The present study demonstrated that intravenous infusion of high doses of nicardipine had significantly beneficial effects on development of brain ischemia and angiographic vasospasm after aneurysmal SAH. Early treatment with nicardipine might be essential to prevent delayed cerebral vasospasm.

Effect of nicardipine on gastric acid secretion in man.

The effect of nicardipine on basal and pentagastrin-stimulated gastric acid secretion in normal volunteers was investigated. When compared with saline, an intravenous infusion of nicardipine caused a significant decrease in peak acid output (from 37.8 mmol hour-1 to 28.8 mmol hour-1; P = 0.04) and a small reduction in aspirate volume. Nicardipine had no significant action on basal acid output or volume of aspirate. Proteolytic activity in both the basal and stimulated periods was unaffected by nicardipine as were serum gastrin concentrations. Although calcium channel blocking agents are theoretically antisecretory the present study suggests they are unlikely to have clinically useful therapeutic actions.

Renal effects of nicardipine in essential hypertension: differences between acute and chronic therapy.

Previous reports have described improvements in renal function with acute administration of nicardipine. The purpose of this study was to determine if these improvements persist with continued treatment. Using single dose radio-isotopic techniques in six subjects with essential hypertension, evaluations of glomerular filtration rate and effective renal plasma flow were made prior to treatment during an intravenous nicardipine infusion of 80 micrograms/kg per h, and following 6 weeks of treatment with 30-40 mg, three times a day. Subjects were stabilized on a diet containing 100 mmol Na+, 80 mmol K+ and 1650 ml water. Blood pressure was similarly reduced with both acute (-45/26 mmHg) and chronic (-42/21 mmHg) therapy. Renal vascular resistance index fell with both acute (-39%) and chronic (-26%) treatment. Significant increases in effective renal plasma flow (+15%), urine volume (+121%), and urinary sodium (+168%) and calcium (+128%) elimination were seen with acute treatment. These parameters had returned to control levels after 6 weeks of treatment. No change was seen in glomerular filtration rate, filtration fraction, plasma renin activity or plasma aldosterone concentration. These data showed that the natriuresis and diuresis as well as the increase in effective renal plasma flow seen with the introduction of nicardipine therapy, did not persist during long-term treatment. There was no evidence of deterioration in any aspect of renal function during long-term therapy despite the significant reduction in renal perfusion pressure.