Dantrolene mediates vasorelaxation in cerebral vasoconstriction: a case series

Neurocrit Care. 2009;10(1):116-21. doi: 10.1007/s12028-008-9132-5. Epub 2008 Aug 12.

Abstract

Introduction: Cerebral vasoconstriction syndromes such as vasospasm after subarachnoid hemorrhage (SAH) and trauma, or Call-Fleming syndrome are difficult to treat, and can lead to substantial disability and death. Dantrolene, a ryanodine receptor antagonist, inhibits intracellular calcium release from the sarco-endoplasmic reticulum. We examined the effect of dantrolene on middle cerebral artery (MCA) blood flow velocities as measured by transcranial Doppler (TCD).

Methods: Three consecutive patients with elevated MCA TCD velocities receiving dantrolene (2.5 mg/kg i.v. q6h) were retrospectively reviewed. Average MCA peak systolic, mean flow velocities, and the pulsatility index (PI) before and after the dantrolene infusion were compared within patients. Systemic physiological parameters (blood pressure, heart rate, central venous pressure, intracranial pressure, body temperature, and cooling water temperature) were retrospectively collected 6 h before and after the dantrolene infusion.

Results: MCA peak systolic velocities (mean +/- SE) for the three patients were 297 +/- 3, 248 +/- 8, and 268 +/- 19 cm/s before dantrolene and 159 +/- 9, 169 +/- 8, and 216 +/- 12 cm/s after dantrolene. Average mean flow velocities showed the same trend. Interestingly, the PI increased slightly from 0.6, 0.52, and 0.67 before dantrolene, to 1.17, 0.71, and 0.77 after dantrolene. Systemic physiological parameters remained stable in all three patients.

Conclusion: Dantrolene attenuated cerebral vasoconstriction as measured by TCD without altering systemic physiological parameters. This suggests that intracellular calcium release from ryanodine channels in smooth muscle might play a role in vasospasm. A prospective study is underway to test this hypothesis.

Publication types

  • Case Reports
  • Research Support, N.I.H., Extramural

MeSH terms

  • Adult
  • Dantrolene / pharmacology*
  • Dantrolene / therapeutic use
  • Female
  • Humans
  • Male
  • Middle Aged
  • Middle Cerebral Artery / diagnostic imaging
  • Middle Cerebral Artery / drug effects*
  • Muscle Relaxants, Central / pharmacology*
  • Muscle Relaxants, Central / therapeutic use
  • Regional Blood Flow / drug effects
  • Subarachnoid Hemorrhage / complications
  • Subarachnoid Hemorrhage / diagnostic imaging
  • Subarachnoid Hemorrhage / therapy
  • Ultrasonography
  • Vasodilation / drug effects*
  • Vasospasm, Intracranial / diagnostic imaging
  • Vasospasm, Intracranial / drug therapy*
  • Vasospasm, Intracranial / etiology

Substances

  • Muscle Relaxants, Central
  • Dantrolene