Atorvastatin decreases computed tomography and S100-assessed brain ischemia after subarachnoid aneurysmal hemorrhage: a comparative study

Crit Care Med. 2012 Feb;40(2):594-602. doi: 10.1097/CCM.0b013e31822f05e7.

Abstract

Objective: Statins, which improve the bioavailability of endogenous nitric oxide and upregulate endothelial nitric oxide synthase, have been used to prevent cerebral vasospasm after aneurysmal subarachnoid hemorrhage. The objective of this study was to determine whether statin therapy diminished vasospasm-induced ischemia as assessed using daily measurements of serum S100B, a biomarker for cerebral ischemia, and computed tomography measurement of ischemic lesion volume.

Design: Single-center study of cases and historical controls.

Setting: Neurointensive care unit in a university hospital.

Patients: Consecutive patients with aneurysmal subarachnoid hemorrhage treated with clipping or coiling within 96 hrs of symptom onset (n = 278) were included from April 2004 to October 2007.

Intervention: Oral atorvastatin, 40 mg/day for 21 days, was used routinely starting on December 1, 2005, in 142 patients, who were compared with the 136 patients managed earlier.

Measurements and main results: Ischemic lesion size was measured using computed tomography on the last available scan and serum S100B was assayed daily for 15 days after admission. Angiographic narrowing was semiquantitatively assessed in patients with vasospasm. In the overall population, cerebral vasospasm was significantly less common in the statin-treated group. Severity of vasospasm, as assessed on the most severe angiogram, was lowered with statin. Statins significantly reduced volume of ischemia in patients with vasospasm and an uncomplicated coiling procedure. S100B levels were significantly lower in statin-treated patients, and the decrease was greatest among high-grade patients (World Federation of Neurological Surgeons 3-5). No differences were found between statin-treated and untreated groups regarding rescue therapy intensity or 1-yr clinical outcomes.

Conclusions: Atorvastatin reduces the incidence, the severity and the ischemic consequences of vasospasm as assessed on computed tomography. In high-grade World Federation of Neurological Surgeons patients, atorvastatin decreases serum levels of S100B, a biomarker of brain ischemia. Despite these positive effects on biomarkers, no improvement of outcome was seen in the overall population, although there was a tendency for a better clinical outcome in high-grade patients.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Atorvastatin
  • Biomarkers / blood
  • Brain Ischemia / diagnosis*
  • Brain Ischemia / drug therapy*
  • Brain Ischemia / etiology
  • Case-Control Studies
  • Confidence Intervals
  • Critical Care / methods
  • Critical Illness / mortality
  • Critical Illness / therapy
  • Female
  • Follow-Up Studies
  • Glasgow Coma Scale
  • Heptanoic Acids / administration & dosage*
  • Hospitals, University
  • Humans
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / administration & dosage
  • Intensive Care Units
  • Male
  • Middle Aged
  • Nerve Growth Factors / blood*
  • Predictive Value of Tests
  • Pyrroles / administration & dosage*
  • Retrospective Studies
  • Risk Assessment
  • S100 Calcium Binding Protein beta Subunit
  • S100 Proteins / blood*
  • Severity of Illness Index
  • Statistics, Nonparametric
  • Subarachnoid Hemorrhage / complications
  • Subarachnoid Hemorrhage / diagnosis*
  • Survival Rate
  • Tomography, X-Ray Computed / methods
  • Treatment Outcome
  • Vasospasm, Intracranial / drug therapy
  • Vasospasm, Intracranial / prevention & control

Substances

  • Biomarkers
  • Heptanoic Acids
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors
  • Nerve Growth Factors
  • Pyrroles
  • S100 Calcium Binding Protein beta Subunit
  • S100 Proteins
  • S100B protein, human
  • Atorvastatin