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Safety and Clinical Effects of Switching From Intravenous to Oral Nimodipine Administration in Aneurysmal Subarachnoid Hemorrhage.

ABSTRACT: Objective: Several guidelines recommend oral administration of nimodipine as vasospasm prophylaxis after aneurysmal subarachnoid hemorrhage (SAH). However, in clinical practice, the drug is administered orally and intravenously (i.v.), depending on clinical conditions and local treatment regimens. We have therefore investigated the safety and clinical effects of switching from i.v. to oral nimodipine therapy. Methods: Patients with aneurysmal SAH between January 2014 and April 2018 and initial i.v. nimodipine therapy, which was subsequently switched to oral administration, were included in this retrospective study. Transcranial Doppler sonography (TCD) of the vessels of the anterior circulation was performed daily. The occurrence of vasospasm and infarction during the overall course of the treatment was recorded. Statistical level of significance was set to p < 0.05. Results: A total of 133 patients (mean age 55.8 years, 65% female) initially received nimodipine i.v. after aneurysmal SAH, which was subsequently switched to oral administration after a mean of 12 days. There were no significant increases in mean flow velocities on TCD after the switch from i.v. to oral nimodipine administration regarding the anterior cerebral artery. For the middle cerebral artery, an increase from 62.36 to 71.78 cm/sec could only be detected in the subgroup of patients with infarction. There was no clustering of complicating events such as new-onset vasospasm or infarction during or after the switch. Conclusions: Our results do not point to any safety concerns when switching nimodipine from initial i.v. to oral administration. Switching was neither associated with clinically relevant increases in TCD velocities nor other relevant adverse events.

SUBMITTER: Gottsche J

PROVIDER: S-EPMC8636241 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundNimodipine improves outcomes following aneurysmal subarachnoid hemorrhage (aSAH). Guidelines recommend that all patients should receive a fixed-dose nimodipine for 21 days. However, studies reported variability of nimodipine concentrations in aSAH. It is not clear if reduced systemic exposure contributes to worsening outcomes. The aim of this study was to compare nimodipine systemic exposure in those who experienced poor outcomes to those who experienced favorable outcomes.MethodsThis was a pilot prospective observational study in 30 adult patients admitted to the University of Alberta Hospital with aSAH. Data were collected from the electronic health records following enrollment. Blood samples were collected around one nimodipine 60 mg dose at a steady state, and nimodipine [total, (+)-R and (-)-S enantiomers] plasma concentrations were determined. The poor outcome was defined as a modified Rankin Scale (mRS) score at 90 days of 3-6, while the favorable outcome was an mRS score of 0-2. The correlation between nimodipine concentrations and percent changes in mean arterial pressure (MAP) before and after nimodipine administration was also determined. Furthermore, covariates potentially associated with nimodipine exposure were explored.ResultsIn total, 20 (69%) participants had favorable outcomes and 9 (31%) had poor outcomes. Following the exclusion of those with delayed presentation (>96 h from aSAH onset), among those presented with the World Federation of Neurological Surgeons (WFNS) grade 3-5, nimodipine median (interquartile range) area under the concentration time curve (AUC0-3h) in those with favorable outcomes were 4-fold higher than in those with poor outcomes [136 (52-192) vs. 33 (23-39) ng.h/mL, respectively, value of p = 0.2]. On the other hand, among those presented with WFNS grade 1-2, nimodipine AUC0-3h in those with favorable outcomes were significantly lower than in those with poor outcomes [30 (28-36) vs. 172 (117-308) ng.h/mL, respectively, value of p = 0.03)]. (+)-R-nimodipine AUC0-3h in those who did not develop vasospasm were 4-fold significantly higher than those who had vasospasm (value of p = 0.047). (-)-S-nimodipine was significantly correlated with percentage MAP reduction. Similar results were obtained when the whole cohort was analyzed.ConclusionThe study was the first to investigate the potential association between nimodipine exposure following oral dosing and outcomes. In addition, it suggests differential effects of nimodipine enantiomers, shedding light on the potential utility of nimodipine enantiomers. Larger studies are needed.

Project description:ObjectiveIn clinical practice, nimodipine is used to control cerebral vasospasm (CVS), which is one of the major causes of severe disability and mortality in patients with aneurysmal subarachnoid hemorrhage (aSAH). However, the exact efficacy of nimodipine use for patients with aSAH is still controversial due to the lack of sufficient and up-to-date evidence.MethodsIn this meta-analysis, the latest databases of the Cochrane Central Register of Controlled Trials, PubMed-Medline, Web of Science, Embase, Scopus, and OVID-Medline were comprehensively searched for retrieving all randomized controlled trials (RCTs) regarding the efficacy of nimodipine in patients with aSAH. The primary outcome was a poor outcome, and the secondary outcomes were mortality and cerebral vasospasm (CVS). After detailed statistical analysis of different outcome variables, further evidence quality evaluation and recommendation grade assessment were carried out.ResultsApproximately 13 RCTs met the inclusion criteria, and a total of 1,727 patients were included. Meta-analysis showed that a poor outcome was significantly reduced in the nimodipine group [RR, 0.69 (0.60-0.78); I2 = 29%]. Moreover, nimodipine also dramatically decreased the mortality [RR, 0.50 (0.32-0.78); I2 = 62%] and the incidence of CVS [RR, 0.68 (0.46-0.99); I2 = 57%]. Remarkably, we found a poor outcome and mortality were both significantly lower among patients with aSAH, with the mean age < 50 than that mean age ≥ 50 by subgroup analysis. Furthermore, the evidence grading of a poor outcome and its age subgroup in this study was assessed as high.ConclusionNimodipine can significantly reduce the incidence of a poor outcome, mortality, and CVS in patients with aSAH. Moreover, we strongly recommend that patients with aSAH, especially those younger than 50 years old, should use nimodipine as early as possible in order to achieve a better clinical outcome, whether oral medication or endovascular direct medication.Systematic review registrationwww.york.ac.uk/inst/crd, identifier: CRD42022334619.

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Safety and Clinical Effects of Switching From Intravenous to Oral Nimodipine Administration in Aneurysmal Subarachnoid Hemorrhage.

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