Cerebrospinal Fluid Concentrations of Nimodipine Correlate With Long-term Outcome in Aneurysmal Subarachnoid Hemorrhage: Pilot Study

Abstract

Objectives The aim was to evaluate plasma and cerebrospinal fluid (CSF) nimodipine concentrations in patients with aneurysmal subarachnoid hemorrhage and their correlation with clinical outcome. Methods Nimodipine infusion was started at 1 mg/h and increased up to 2 mg/h and continued up to 21 days in surviving patients. Arterial and CSF samples were collected at least after 24 hours of stable nimodipine dosing. Delayed cerebral ischemia and vasospasm were documented by new neurological deficits and neuroimaging. The clinical outcome was assessed at 9 months by the modified Rankin scale. Results Twenty-three patients were enrolled. Nimodipine dose was 13 to 38 μg/kg per hour. Nimodipine arterial and CSF concentrations were 24.9 to 71.8 ng/mL and 37 to 530 pg/mL, respectively. Dose did not correlate with arterial or CSF concentrations. Arterial concentrations did not correlate with corresponding CSF concentrations. Doses and arterial concentrations did not correlate with the clinical outcome and were not associated with the occurrence of delayed cerebral ischemia. However, patients with no significant disability after 9 months of hemorrhage showed significantly higher CSF nimodipine concentrations (P = 0.015) and CSF-to-plasma ratios (P = 0.011) compared with patients who showed some degree of disability or who died. Conclusions Cerebrospinal fluid nimodipine concentrations measured during hospital drug infusion showed a correlation with long-term clinical outcome in patients with aneurysmal subarachnoid hemorrhage. These very preliminary data suggest that CSF concentrations monitoring may have some value in managing these patients.

Nimodipine Pharmacokinetic Variability in Various Patient Populations

“…Therefore, it is not clear if all patients are getting the full benefit of nimodipine using a fixed dose regimen and the evidence supporting a correlation between nimodipine concentrations and patient outcomes is scarce and not clear. Riva et al have reported an association between nimodipine CSF concentrations and neurological outcomes at 9 months following SAH onset but they were unable to find such correlation with plasma concentrations [62]. It should be noted, however, that all patients were dosed using nimodipine IV infusion and their plasma concentrations ranged from 24.9 to 71.8 ng/ mL, concentrations way above what has been reported in some patients given oral dosing [23,56].…”

The Impact of Nimodipine Administration through Feeding Tube on Outcomes in Patients with Aneurysmal Subarachnoid Hemorrhage

“…None of those studies, however, has reported a correlation between reduced exposure and patient outcomes. Riva et al have reported an association between nimodipine cerebrospinal fluid concentrations and neurological outcomes at 9 months following SAH onset but they were unable to find such correlation with plasma concentrations (14). It should be noted, however, that all their patients were dosed using nimodipine IV infusion and their plasma concentrations ranged from 24.9 to 71.8 ng/ml, concentrations way above what has been reported in patients given oral dosing (17,19).…”

“…It is not clear, however, whether this technique of administration result in reduced clinical effectiveness and in turn poor outcomes. Although the evidence supporting a correlation between nimodipine plasma concentrations and patient outcomes is scarce and not clear, lack of absorption definitely denies the benefits of any drug used systemically (14). Therefore, the present study aimed to answer the following research question: Among SAH patients, is taking nimodipine by enteral feeding tube associated with worse outcomes compared to those who swallow nimodipine whole tablets?…”

Strategies for Neuroprotection in Multiple Sclerosis and the Role of Calcium

“…It can cross the BBB and enter the CNS [197]. A recent study has demonstrated a direct correlation between the concentration of nimodipine in cerebrospinal fluid, but not in arterial blood, and the disease outcome after subarachnoid hemorrhage [198]. These data may indicate a protective effect of nimodipine.…”