Mg Of Nicardipine Research Articles

Localized Nicardipine Release Implants for Prevention of Vasospasm After Aneurysmal Subarachnoid Hemorrhage

Cerebral vasospasm largely contributes to a devastating outcome after aneurysmal subarachnoid hemorrhage (aSAH), with limited therapeutic options. To investigate the safety and efficacy of localized nicardipine release implants positioned around the basal cerebral vasculature at risk for developing proximal vasospasm after aSAH. This single-masked randomized clinical trial with a 52-week follow-up was performed between April 5, 2020, and January 23, 2023, at 6 academic neurovascular centers in Germany and Austria. Consecutive patients with World Federation of Neurological Surgeons grade 3 or 4 aSAH due to a ruptured anterior circulation aneurysm requiring microsurgical aneurysm repair participated. During aneurysm repair, patients were randomized 1:1 to intraoperatively receive 10 implants at 4 mg of nicardipine each plus standard of care (implant group) or aneurysm repair alone plus standard of care (control group). The primary end point was the incidence of moderate to severe cerebral angiographic vasospasm (aVS) between days 7 and 9 after aneurysm rupture as determined by digital subtraction angiography. Of 41 patients, 20 were randomized to the control group (mean [SD] age, 54.9 [9.1] years; 17 female [85%]) and 21 to the implant group (mean [SD] age, 53.6 [11.9] years; 14 female [67%]). A total of 39 patients were included in the primary efficacy analysis. In the control group, 11 of 19 patients (58%) developed moderate or severe aVS compared with 4 of 20 patients (20%) in the implant group (P = .02). This outcome was paralleled by a lower clinical need for vasospasm rescue therapy in the implant group (2 of 20 patients [10%]) compared with the control group (11 of 19 patients [58%]; P = .002). Between days 13 and 15 after aneurysm rupture, new cerebral infarcts were noted in 6 of 19 patients (32%) in the control group and in 2 of 20 patients (10%) in the implant group (P = .13). At 52 weeks, favorable outcomes were noted in 12 of 18 patients (67%) in the control group and 16 of 19 patients (84%) in the implant group (P = .27). The adverse event rate did not differ between groups. These findings show that placing nicardipine release implants during microsurgical aneurysm repair can provide safe and effective prevention of moderate to severe aVS after aSAH. A phase 3 clinical trial to investigate the effect of nicardipine implants on clinical outcome may be warranted. ClinicalTrials.gov Identifier: NCT04269408.

Systematic Review of Intrathecal Nicardipine for the Treatment of Cerebral Vasospasm in Aneurysmal Subarachnoid Hemorrhage.

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

Development of Nicardipine Prolonged-Release Implants After Clipping for Preventing Cerebral Vasospasm: From Laboratory to Clinical Trial

We have developed a drug delivery system using a vasodilating drug that can be implanted intracranially at the time of surgery for aneurysm clipping, without systemic side effects or side effects associated with long-term intrathecal drug administration. We started our project on 1994 for making a slowly releasing drug delivery system in vitro because cerebral vasospasm occurs 4–14 days following subarachnoid hemorrhage (SAH). A rod-shaped pellet containing 1 mg of nicardipine for animal study was prepared by heat compression. We presented the efficacy and safety of this drug delivery system using both canine double-hemorrhage and clot placement models. Since October 1999, nicardipine prolonged-release implants (NPRIs) containing 4 mg of nicardipine have been used to prevent vasospasm in patients with SAH. NPRIs were placed in the cistern of the cerebral arteries, where thick clots existed; therefore, vasospasm related to delayed ischemic neurological deficits (DINDs) was highly probable. Vasospasm was completely prevented in the arteries by placing NPRIs adjacent to the arteries during surgery. No complications were experienced. We have performed three studies (a single-center study with consecutive patients; a single-center, randomized, double-blind trial; and a multicenter cooperative study) and have proved that implantation of NPRIs reduces the incidence of cerebral vasospasm and DINDs and improves clinical outcome after SAH.

Nicardipine Prolonged-Release Implants for Preventing Cerebral Vasospasm After Subarachnoid Hemorrhage: Effect and Outcome in the First 100 Patients

Vasospasm following subarachnoid hemorrhage (SAH) remains difficult to prevent despite extensive investigative efforts. Nicardipine prolonged-release implants (NPRIs) have been used to prevent vasospasm in patients with SAH since October 1999. The present study analyzed the efficacy and safety of NPRIs in 100 patients with SAH and thick subarachnoid clot (mainly Fisher group 3) treated with NPRIs (diameter 2 mm, length 10 mm, containing 4 mg of nicardipine) during surgery after clipping of the aneurysm. The number and location of pellets depended on the amount and site of the subarachnoid clot on preoperative computed tomography and on the type of craniotomy. Two to 12 pellets were implanted in the cisterns of the internal carotid artery, middle cerebral artery, and/or anterior cerebral artery, where thick clots were present and vasospasm related to delayed ischemic neurological deficit (DIND) was highly likely. Only seven patients developed DIND and five patients suffered cerebral infarction. Angiography performed on days 7-12 revealed no vasospasm in any of the arteries close to the site of NPRI placement. NPRI placement can completely prevent vasospasm in arteries within the cisterns containing thick clots, but is less effective in remote locations.

重症くも膜下出血の治療―ニカルジピン徐放剤を用いて―

Nicardipine prolonged-release pellets (NP) are made for implantation during surgery to prevent cerebral vasospasm. We retrospectively analyzed patients with a poor-grade subarachnoid hemorrhage (SAH) between October 1999 and September 2004. Among 125 surgically treated SAH patients, 34 belonged to WFNS grades 4 and 5 (male/female 13/21, the average age was 63, the ratio craniotomy/coil 26/8). Four to 12 NPs (16-48 mg of nicardipine) were placed along the respective artery (IC, A1, A2, A3, M1, M2, and M3) after clipping the aneurysm, where there was thick clot and therefore subsequent vasospasm was highly likely. The intracranial pressure was monitored and treated with glycerin, ventricular drainage, external decompression, and/or barbiturate administration. Neither induced hypervolemia nor induced hypertension was used. A delayed ischemic neurological deficit was seen in 1 patient, but there were no cerebral infarctions due to cerebral vasospasm. Angiography performed on days 7-12 revealed no vasospasm in any arteries close to where the NPs were placed. The outcome after 3 months was good in 7, moderately disabled in 13, severely disabled in 7, vegetative state in 2, and 5 patients had deceased. The NP is an effective, simple, and safe prophylactic treatment to prevent vasospasm when a surgical procedure is chosen to treat ruptured aneurysms of poor-grade SAH patients.

Efficacy and Safety of Nicardipine Prolonged-Release Implants for Preventing Vasospasm in Humans

Despite extensive investigative efforts, there are few treatments that can prevent vasospasm after subarachnoid hemorrhage. This study was conducted to examine the efficacy and safety of nicardipine prolonged-release implants (NPRI) for humans, which have already been proven in dogs. Twenty consecutive subarachnoid hemorrhage patients with thick subarachnoid clot were treated with NPRI (a pellet of diameter 2 mm, length 10 mm, containing 4 mg of nicardipine) during surgery after clipping of their aneurysm. The number and location of pellets depended on the amount and site of subarachnoid clot on preoperative CT and on craniotomy. Two to 10 pellets were implanted in the cistern of the internal carotid, middle cerebral, and/or anterior cerebral artery, where thick clots existed and therefore vasospasm related to delayed ischemic neurological deficits was highly likely. Delayed ischemic neurological deficits and cerebral infarctions were seen in 1 patient. Angiography performed on days 7 to 12 revealed no vasospasm in any arteries near which NPRI were placed. No complications were experienced. Vasospasm was completely prevented for the arteries in thick clot cisterns, when NPRI were placed adjacent to the arteries during surgery. This drug-delivery system offers a promising approach for preventing vasospasm.

Intrathecal administration of nicardipine hydrochloride to prevent vasospasm in patients with subarachnoid hemorrhage.

To evaluate the prophylactic effect of repeated intrathecal administration of nicardipine associated with hypertensive hypervolemic hemodilution therapy (triple H) and sodium correction, we analyzed a consecutive series of 177 patients with subarachnoid hemorrhage. All patients received aneurysmal clipping and placement of cisternal drainage within 48 hours of the onset. Intrathecal administration of 4 mg of nicardipine was performed every 12 h. Nicardipine concentrations in the cerebrospinal fluid (CSF) and blood before and after its administration were analyzed. Angiographic vasospasm (aVS), symptomatic VS (sVS), and clinical outcome 6 months after onset were also evaluated. Nicardipine concentration in CSF on day 9 was 231.44 +/- 51.51 ng/ml (mean +/- SD), and that of blood was 21.05 +/- 15.57 ng/ml. Twenty patients (11.3%) showed aVS, and ten of those (5.7%) showed sVS (six were transient and four were permanent). Those with good outcome (assessed as good recovery and moderately disabled) 6 months after onset were 89.2% of the total. The number of patients requiring a shunt operation was 33 of 177 (18.6%), and 11 patients presented intracranial infection. These results suggest that our strategy may well prevent VS. However, hydrocephalus and infection may be serious disadvantages that should be resolved.

Aortic arch repair using hypothermic circulatory arrest technique associated with pharmacological brain protection.

Hypothermic circulatory arrest is a standard procedure for the treatment of aortic arch. However, there is a time limit for this procedure. There is now an urgent need to develop prophylactic measures to extend the time limit. We have used a pharmacological mixture of thiopental, nicardipine and mannitol for all patients undergoing circulatory arrest since 1991 to extend the safe limit. The purpose of this study was to analyze the neurological complications demonstrated by these patients and to evaluate the brain-protective effects of our measure. The clinical records of 75 consecutive patients undergoing an aortic arch repair using a hypothermic circulatory arrest technique during the past 8 years were retrospectively reviewed. Systemic cooling was continued until a total disappearance of EEG activity. Prior to circulatory arrest, 15 or 30 mg/kg of thiopental, 20 mg of nicardipine and 300 ml of mannitol were infused into the venous reservoir of a cardiopulmonary bypass circuit. Graft replacement was performed in all patients and the extent of replacement was a total aortic arch in 43 patients, a distal aortic arch in 17, a hemiarch in 13 and a distal aortic arch and a total descending aorta in two. The duration of circulatory arrest ranged from 16 to 80 min (mean 41.5 min), and it exceeded 45 min in 37 patients. Operative mortality was 10.7% and two patients died of stroke. Three patients had permanent and three other patients had transient neural deficits. The incidence of stroke was 8.0% as a whole, and no correlation between the incidence of neurological complications and the duration of circulatory arrest was found. A multivariate analysis showed that the duration of circulatory arrest was determined as a predictor of neither operative mortality nor postoperative stroke. The findings of the present study suggest that our pharmacological brain protection appears to be effective for safely extending hypothermic circulatory arrest.

Intravenous nicardipine in the treatment of postoperative arterial hypertension

Background: Calcium entry blockers are commonly used in the management of postoperative hypertension. The hemodynamic and blood gas effects of nicardipine, a dihydropyridine derivative available intravenously, were studied in patients after abdominal aortic surgery. Methods: Sixteen patients (66 ± 8 years) who developed arterial hypertension (mean arterial pressure, >90 mmHg) after abdominal aortic aneurysm reconstruction were studied. Fourteen patients had already been treated with a sodium nitroprusside infusion, the doses of which were maintained constant (mean dose: 1.42 ± 1.04 μg/kg/min). Hemodynamic and blood gas data were collected at baseline, 15 minutes, and 45 minutes after a slow bolus administration of 3 to 5 mg of nicardipine. Results: After the nicardipine administration, mean arterial pressure decreased from 101 ± 11 to 83 ± 11 mmHg ( p < 0.001), and the cardiac index acutely increased from 3.96 ± 0.74 to 4.57 ± 0.83 L/min/m 2 ( p < 0.05). Systemic vascular resistance significantly decreased. There were no significant changes in heart rate, stroke volume, cardiac filling pressures, pulmonary artery pressures, pulmonary vascular resistance, left ventricular stroke work, or right ventricular stroke work. One patient developed acute pulmonary edema, associated with a dramatic increase in cardiac filling pressures, and electrocardiographic signs of myocardial ischemia. Nicardipine administration was also associated with an acute reduction in Pao 2 from 85.0 ± 12.1 mmHg to 70.3 ± 9.2 mmHg ( p < 0.001), associated with an increase in venous admixture from 21.7% ± 3.2% to 28.0% ± 5.2% ( p < 0.01). Oxygen delivery increased moderately and oxygen extraction decreased, but oxygen consumption was unchanged. Conclusion: This study confirms the excellent efficacy of nicardipine in the management of postoperative hypertension, but underlines the risk of poor cardiac tolerance in patients after major surgery. Although oxygen delivery to the cells is usually well preserved, nicardipine can also significantly alter blood oxygenation by increasing ventilation/perfusion mismatch.

Effects of double administration of nicardipine of the cardiovascular response to tracheal intubation in hypertensive patients.

The efficacy of intravenous nicardipine in attenuating the cardiovascular responses to laryngoscopy and tracheal intubation was studied in 20 hypertensive patients. Ten patients received intravenous 1 mg of nicardipine 1 min before induction (N1 group). The other ten received 1 mg of nicardipine 1 min before induction and an additional 1 mg just before laryngoscopy (N2 group). In the N1 group, arterial pressure and heart rate increased significantly after tracheal intubation. In the N2 group, arterial pressure did not increase but heart rate increased more than that in N1 group. There was no significant difference in rate pressure product between the two groups.

Effect of Nicardipine on Essential Tremor

The effects of nicardipine, a calcium channel blocker (CCB), were investigated in 11 patients with essential tremor (ET). In a placebo controlled study, a single oral dose of 30 mg of nicardipine was administered, followed by 1 month of sustained treatment (60 mg/day). Tremor was assessed by accelerometric recording. A single oral dose of nicardipine reduced the tremor amplitude respect baseline (p = 0.003) and placebo (p = 0.008). After 1 month of chronic treatment, nicardipine still reduced the tremor amplitude (30.78% +/- 17.13 SE from baseline), but failed to sustain the initial statistical improvement. A single oral dose of nicardipine is effective in reducing ET.

Platelet antiaggregate activity

Calcium ions act as a second messenger to platelet agonists, with increases in intracellular calcium bringing about changes in shape, aggregation, and release reactions. Changes in platelet function have been reported previously in migraine sufferers and there is evidence that hyperaggregability occurs during a migraine attack. It was decided to assess platelet aggregation with platelet-rich plasma (PRP) from nicardipine-treated migraine sufferers because dihydropyridine derivatives are known to inhibit adenosine diphosphate (ADP)- and epinephrine-induced aggregation. Aggregation induced by 1.4 μmol/L arachidonic acid was similar in PRP from control subjects and untreated migraine sufferers, whereas 1 or 2 μmol/L ADP-induced aggregation was lower in PRP from migraine sufferers. Treatment with 20 mg of nicardipine three times daily for 2 months significantly ( p < 0.05) increased 2 μmol/L ADP-induced aggregation. It is concluded that nicardipine was acting either on migraine pathogenic mechanisms or directly on the platelets.

Acute pharmacokinetic and hemodynamic effects of intravenous bolus dosing of nicardipine

The antihypertensive effects, duration of action, and pharmacokinetics of intravenous bolus doses of nicardipine were investigated in a series of patients with mild-to-moderate hypertension. Patients with a supine diastolic blood pressure between 95 and 114 mm Hg and a heart rate less than 90 beats/min who received no other antihypertensive medications were included in the study. On separate study days, single intravenous bolus doses of 0.125, 0.25, 0.5, 1, 3, 5, and 7 mg of nicardipine were administered over a 2-minute period. Blood pressure and heart rate were measured for 6 hours after an intravenous bolus of nicardipine was given, and serum nicardipine levels were measured throughout the study. Although the antihypertensive effect occurred immediately during the bolus infusion, peak average decreases in systolic and diastolic pressure ranged from 20 to 25 and 15 to 44 mm Hg, respectively, and occurred 2.5 +/- 0.6 minutes after infusion. Heart rate increased by 12 to 40 beats/min during the peak effect. The mean duration of action after an intravenous bolus dose was 24 +/- 5 minutes. A dose-response relationship was observed, as both nicardipine dosage and plasma nicardipine concentration correlated with reduction in blood pressure. These data indicate that bolus administration of nicardipine may provide a practical approach for the rapid parenteral treatment of hypertensive states.

Intravenous nicardipine for treatment of intraoperative hypertension during abdominal surgery

Twenty patients, American Society of Anesthesiologists class I or II, who developed intraoperative hypertension (mean arterial pressure greater than 110 mm Hg) during abdominal surgery under balanced general anesthesia were randomly assigned to two groups. The nicardipine group (n = 10) received 5 mg of nicardipine hydrochloride, and the placebo group (n = 10) received 5 mL of nicardipine solvent injected intravenously over a 5-minute period in a blind manner. Arterial pressure was recorded for 15 minutes after the injection was started. If the mean arterial pressure did not decrease at least 10% at 15 minutes, the trial was opened and patients received 5 mg of nicardipine. None of the patients in the nicardipine group received nicardipine in an open manner, in contrast with 7 of the 10 patients in the placebo group (P less than 0.03, Fisher exact test). During both the blind period and the open trial, nicardipine induced a 34% decrease in systolic, diastolic, and mean arterial pressure. Minimal values of pressure were noted at 6 minutes; however, arterial pressure remained below the pre-nicardipine injection values and near preoperative values for 45 minutes. No severe hypotension was observed, but the nicardipine injection was stopped at 3 mg in two cases during the blind period because of the rate of pressure reduction. Heart rate remained unchanged during the decrease in arterial pressure in both groups. This study indicates that nicardipine is an effective, long lasting, and safe therapy for intraoperative hypertension during abdominal surgery.

Usefulness of nicardipine as monotherapy for chronic, stable angina

Using a double-blind, Latin square protocol designed to detect dose response, nicardipine hydrochloride, a new calcium antagonist, was studied as monotherapy for stable exertional angina. Eighty-one patients were enrolled in the trial and 62 patients were included in ≥1 primary efficacy analyses. Patients received 1 to 2 weeks of placebo run-in, then 5 weeks of treatment with placebo and with 10, 20 and 30 mg of nicardipine given 3 times daily. Patients completed symptom diaries, were monitored with 24-hour electrocardiographic Holter monitors and underwent serial exercise treadmill tests. By 1 hour, 10, 20 and 30 mg of nicardipine administered 3 times daily produced statistically significant, dose-related improvements in all key exercise parameters, which persisted at the 4-hour evaluation. The systolic blood pressure at rest and during exercise decreased, but the pulse slightly increased. The peak rate-pressure product was unchanged. The side effects were not severe. Nicardipine hydrochloride is an effective, well-tolerated medication for the treatment of stable exertional angina, and is a good alternative to currently available calcium antagonists.

The acute haemodynamic effects of nicardipine in patients with chronic left ventricular failure.

Nicardipine is a new slow channel calcium blocker. It has been shown to be effective in the treatment of hypertension and angina pectoris. Nine patients with mild to moderate left ventricular failure were given intravenous infusions of nicardipine and the haemodynamic effects measured. In patients receiving 20 mg of nicardipine, mean cardiac index rose to a peak 1.81 X min-1 X m-2 (64%) above the preinfusion level, stroke volume index rose by 12 ml X m-2 (35%) and heart rate rose by 16 beats X min-1 (20%). There was a significant fall in systemic vascular resistance of 50% manifested by a reduction of 22 mm Hg in systolic blood pressure (18%) and 18 mm Hg in diastolic blood pressure (22%). Pulmonary vascular resistance fell by 45%. Mean pulmonary artery pressure and capillary wedge pressure did not change significantly. This study suggests that concomitant mild to moderate left ventricular failure is not a contra-indication to nicardipine therapy in patients with angina.

Short- and long-term efficacy of nicardipine, assessed by placebo-controlled single- and double-blind crossover trials in patients with chronic stable angina

The efficacy of nicardipine, a new calcium ion antagonist, was studied in 39 patients aged 42 to 70 years with chronic stable angina in two different placebo-controlled single- and double-blind crossover trials and with long-term follow-up, using serial quantitated exercise testing and ambulatory ST segment monitoring. In the first study the minimal effective dose was determined, and in the repeat study the effects of three different dose levels were evaluated. Treadmill exercise testing was performed at the end of each 2 week treatment period with on-line computer analysis of the electrocardiogram. The mean (+/- standard error of the mean) exercise time was 6.8 +/- 0.7 minutes on placebo and 7.0 +/- 0.8 minutes during treatment with nicardipine, 60 mg/day (p = NS). This increased to 8.7 +/- 0.8 (p less than 0.001) and 9.2 +/- 0.9 minutes (p less than 0.001) with 90 and 120 mg/day, respectively. The mean heart rate at rest during placebo administration was 75 +/- 2 beats/min and increased to 85 +/- 3, 84 +/- 2 and 88 +/- 3 beats/min (p less than 0.02, p less than 0.01, p less than 0.01, respectively) at each dose level. The time taken to develop 1 mm of ST segment depression was prolonged from 4.8 +/- 0.6 minutes during placebo administration to 5.3 +/- 0.7 (p = NS), 6.4 +/- 0.7 (p less than 0.01) and 6.7 +/- 0.8 minutes (p less than 0.001), respectively, at each dose level. The improvement achieved after 2 weeks of nicardipine, 120 mg daily, was maintained over a period of 6 months of follow-up. Three patients were withdrawn, one taking 60 mg of nicardipine, one taking 90 mg of nicardipine and one taking placebo, but the overall incidence of side effects was low. Nicardipine is an effective antianginal agent with an optimal dose of 90 to 120 mg/day.