Effects of a single dose of dantrolene in patients with cerebral vasospasm after subarachnoid hemorrhage: a prospective pilot study

Abstract

Background and purpose: New therapies for cerebral vasospasm after subarachnoid hemorrhage are needed because of its high morbidity and mortality rates. We investigated the feasibility and safety of a single dose of intravenous dantrolene and its effect on transcranial Doppler in cerebral vasospasm after subarachnoid hemorrhage.

Methods: In a prospective, open-label, single-dose ascending safety trial, 5 patients received intravenous dantrolene 1.25 mg/kg and the next 5 patients received 2.5 mg/kg over the course of 60 minutes. All other infusions were kept steady and hemodynamic parameters were recorded. Transcranial Doppler was performed at 0, 45, 90, and 135 minutes relative to infusion start. Basic chemistries, serum osmolality, arterial blood gas, and liver enzymes were measured before and after.

Results: Laboratory values and hemodynamic parameters remained unchanged except for a decrease in the systolic blood pressure in the low-dose group (-8 mm Hg; 95% CI, -26 to 10 mm Hg; P=0.027). After correcting for this decrease in blood pressure, peak systolic transcranial Doppler velocities decreased significantly (-26 cm/s; 95% CI, -47 to -5 cm/s; P=0.02), with a borderline change in mean velocities in the low-dose group (-16 cm/s; 95% CI, -36 to 4 cm/s; P=0.07) and peak systolic transcranial Doppler velocity in the high-dose group (-26 cm/s; 95% CI, -56 to 5 cm/s; P=0.05).

Conclusions: In this pilot study, a single dose of intravenous dantrolene in cerebral vasospasm after subarachnoid hemorrhage appears feasible while inhibiting vasoconstriction in the low-dose group, but it may lower blood pressure. Our study provides useful data for the design of larger future studies. Clinical Trial Registration- URL: https://ichgcp.net/clinical-trials-registry/NCT00964548" title="See in ClinicalTrials.gov">NCT00964548.

Conflict of interest statement

Conflict of Interest: None.

Figures

Figure 1. Study design

The study is described in detail in the methods section. Abbreviation: Chem7, basic chemistries.

Figure 2. Screening and enrollment (CONSORT diagram)

A total of 28 patients were approached for consent, of which 24 consented. Ten patients received study drug, while 14 did not for various listed reasons.

Figure 3. Transcranial Doppler flow velocities

Shown are mean changes in PSV and MFV with 95% CI at 45, 90 and 135 minutes from baseline in the vessel of interest (vessel in vasospasm) in the low dose group (all patients, panel A; single low blood pressure outlier excluded, panel B), and high dose group (panel C). Asterix (*) indicate significant changes by repeated measures ANOVA.