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

Stroke. 2011 May;42(5):1301-6. doi: 10.1161/STROKEAHA.110.603159. Epub 2011 Mar 31.

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: http://clinicaltrials.gov. Unique identifier: NCT00964548.

Publication types

  • Clinical Trial
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Blood Pressure / drug effects
  • Blood Pressure / physiology
  • Dantrolene / administration & dosage
  • Dantrolene / adverse effects
  • Dantrolene / therapeutic use*
  • Dose-Response Relationship, Drug
  • Feasibility Studies
  • Female
  • Humans
  • Infusions, Intravenous
  • Male
  • Middle Aged
  • Muscle Relaxants, Central / administration & dosage
  • Muscle Relaxants, Central / adverse effects
  • Muscle Relaxants, Central / therapeutic use*
  • Pilot Projects
  • Prospective Studies
  • Subarachnoid Hemorrhage / complications*
  • Treatment Outcome
  • Ultrasonography, Doppler, Transcranial
  • Vasoconstriction / drug effects
  • Vasoconstriction / physiology
  • Vasospasm, Intracranial / diagnostic imaging
  • Vasospasm, Intracranial / drug therapy*
  • Vasospasm, Intracranial / etiology*

Substances

  • Muscle Relaxants, Central
  • Dantrolene

Associated data

  • ClinicalTrials.gov/NCT00964548