Dantrolene for cerebral vasospasm after subarachnoid haemorrhage: a randomised double blind placebo-controlled safety trial
Authors
Muehlschlegel, SusanneCarandang, 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.
Wakhloo, Ajay K.
Student Authors
Thomas FloodAcademic Program
MD/PhDUMass Chan Affiliations
Department of RadiologyDepartment of Quantitative Health Sciences
Department of Neurology
Document Type
Journal ArticlePublication Date
2014-10-24
Metadata
Show full item recordAbstract
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.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 websiteDOI
10.1136/jnnp-2014-308778Permanent Link to this Item
http://hdl.handle.net/20.500.14038/48029PubMed ID
25344064Related Resources
Link to article in PubMedae974a485f413a2113503eed53cd6c53
10.1136/jnnp-2014-308778