eScholarship@UMMS

Title

Dantrolene for cerebral vasospasm after subarachnoid haemorrhage: a randomised double blind placebo-controlled safety trial

Authors

Susanne Muehlschlegel, University of Massachusetts Medical SchoolFollow
Raphael A. Carandang, University of Massachusetts Medical SchoolFollow
Wiley R. Hall, University of Massachusetts Medical SchoolFollow
Nisha Kini, University of Massachusetts Medical SchoolFollow
Saef Izzy, UMASS Medical SchoolFollow
Bridget Garland, University of Massachusetts Medical SchoolFollow
Cynthia OuilletteFollow
Imramsjah M. J. van der Bom, University of Massachusetts Medical SchoolFollow
Thomas F. Flood, University of Massachusetts Medical SchoolFollow
Matthew J. Gounis, University of Massachusetts Medical SchoolFollow
John P. Weaver, University of Massachusetts Medical SchoolFollow
Bruce A. Barton, University of Massachusetts Medical SchoolFollow
Ajay K. Wakhloo, University of Massachusetts Medical SchoolFollow

UMMS Affiliation

Department of Neurology; Department of Quantitative Health Sciences; Department of Radiology

Publication Date

10-24-2014

Document Type

Article

Disciplines

Neurology | Radiology

Abstract

BACKGROUND: Dantrolene is neuroprotective in animal models and may attenuate cerebral vasospasm (cVSP) in human aneurysmal subarachnoid haemorrhage (aSAH). We evaluated safety, feasibility and tolerability of intravenous dantrolene (IV-D) in patients with aSAH.

METHODS: In this single-centre, randomised, double blind, placebo-controlled trial, 31 patients with aSAH were randomised to IV-D 1.25 mg every 6 h for 7 days (n=16) or equiosmolar free water/5% mannitol (placebo; n=15). Primary safety end points were incidence of hyponatraemia (sNa≤132 mmol/L) and liver toxicity (proportion of patients alanine transaminase, aspartate aminotransferase and AlkPhos >5× upper-limit-of-normal). Secondary end points included tolerability, systemic hypotension and intracranial hypertension. Efficacy was explored for clinical/radiological cVSP, delayed cerebral ischaemia (DCI), and 3-month functional outcomes. Quantitative analyses of angiograms and daily transcranial Doppler (TCD) were performed.

RESULTS: Between IV-D versus placebo, no differences were observed in the primary outcomes (hyponatremia 44% vs 67% (p=0.29); liver toxicity 6% vs 0% (p=1.0)). Three patients in the IV-D versus two in the placebo group had severe adverse events possibly attributable to infusion and reached stop criteria: one IV-D patient developed liver toxicity; two patients in each group developed brain oedema requiring osmotherapy. The majority of adverse events were not related to infusion (17 vs 5 (RR 2.2; 95% CI 0.7 to 6.7; p=0.16) in IV-D vs placebo). No differences in any categorical cVSP outcomes, DCI, 3-month outcomes or quantitative angiogram and TCD analyses were seen in this small safety trial not powered to detect efficacy.

CONCLUSIONS: In this small trial, IV-D after aSAH was feasible, tolerable and safe.

TRIAL REGISTRATION NUMBER: http://clinicaltrials.gov NCT01024972.

DOI of Published Version

10.1136/jnnp-2014-308778

Source

J Neurol Neurosurg Psychiatry. 2014 Oct 24. pii: jnnp-2014-308778. doi: 10.1136/jnnp-2014-308778. [Epub ahead of print]. Link to article on publisher's website

Journal/Book/Conference Title

Journal of neurology, neurosurgery, and psychiatry

Related Resources

Link to article in PubMed

PubMed ID

25344064

Repository Citation

Muehlschlegel, Susanne; Carandang, Raphael A.; Hall, Wiley R.; Kini, Nisha; Izzy, Saef; Garland, Bridget; Ouillette, Cynthia; van der Bom, Imramsjah M. J.; Flood, Thomas F.; Gounis, Matthew J.; Weaver, John P.; Barton, Bruce A.; and Wakhloo, Ajay K., "Dantrolene for cerebral vasospasm after subarachnoid haemorrhage: a randomised double blind placebo-controlled safety trial" (2014). Radiology Publications and Presentations. 136.
https://escholarship.umassmed.edu/radiology_pubs/136