Effects of acute treatment with statins on cerebral autoregulation in patients after aneurysmal subarachnoid hemorrhage.
OBJECTIVE
The authors previously have demonstrated that acute treatment with pravastatin after aneurysmal subarachnoid hemorrhage (SAH) can ameliorate vasospasm-related delayed ischemic neurological deficits (DINDs). In the current study, they test the hypothesis that these effects are associated with improvement in indices describing autoregulation of cerebral blood flow.


METHODS
In this double-blind study, 80 patients between the ages of 18 and 84 years who had aneurysmal SAH were randomized equally to receive either 40 mg of oral pravastatin or placebo once daily for up to 14 days (medication was started 1.8 x 1.3 days after ictus). Autoregulation was measured using a daily transient hyperemic response test (THRT) on transcranial Doppler ultrasonography (800 measurements in 80 patients), and data were compared between the pravastatin and placebo groups and between patients with or without vasospasm, DINDs, or unfavorable outcome. Measurement of autoregulation also was performed using the pressure-reactivity index, a moving correlation coefficient between mean arterial and intracranial pressures (Days 0-5, 132 measurements in 32 patients). There was no difference in baseline autoregulation indices between the trial groups. The members of the pravastatin group not only had a shorter duration of impaired autoregulation but also had stronger transient hyperemic response ratios (THRRs) bilaterally. A negative correlation existed between the mean flow velocity in the middle cerebral artery and THRRs. Onset of DINDs occurred when bilateral autoregulation failed. On Days 3, 4, and 5, the pressure-reactivity index correlated significantly with ipsilateral impaired autoregulation.


CONCLUSIONS
The neuroprotective effects of acute treatment with pravastatin following aneurysmal SAH are associated with enhancement of autoregulation. A routine and daily assessment of cerebral autoregulation by using the THRT may help identify patients at high risk of DINDs.
Tseng
Ming-Yuan
MY
Department of Neurosurgery, Addenbrooke's Hospital, University of Cambridge, United Kingdom. mty22@cam.ac.uk
Czosnyka
Marek
M
Richards
Hugh
H
Pickard
John D
JD
Kirkpatrick
Peter J
PJ
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000783:Aneurysm / Q000503:physiopathology*; D001783:Blood Flow Velocity / Q000187:drug effects; D002540:Cerebral Cortex; D004311:Double-Blind Method; D005260:Female; D006706:Homeostasis / Q000187:drug effects*; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use*; D007427:Intracranial Pressure / Q000187:drug effects; D008297:Male; D008875:Middle Aged; D017035:Pravastatin / Q000627:therapeutic use*; D013345:Subarachnoid Hemorrhage / Q000503:physiopathology*; D013997:Time Factors; D016896:Treatment Outcome; D017585:Ultrasonography, Doppler, Transcranial / Q000379:methods
D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D017035:Pravastatin