Impact of anesthesia on pathophysiology and mortality following subarachnoid hemorrhage in rats

Abstract

BACKGROUND: Anesthesia is indispensable for in vivo research but has the intrinsic potential to alter study results. The aim of the current study was to investigate the impact of three common anesthesia protocols on physiological parameters and outcome following the most common experimental model for subarachnoid hemorrhage (SAH), endovascular perforation. METHODS: Sprague-Dawley rats (n = 38) were randomly assigned to (1) chloral hydrate, (2) isoflurane or (3) midazolam/medetomidine/fentanyl (MMF) anesthesia. Arterial blood gases, intracranial pressure (ICP), mean arterial blood pressure (MAP), cerebral perfusion pressure (CPP), and regional cerebral blood flow (rCBF) were monitored before and for 3 hours after SAH. Brain water content, mortality and rate of secondary bleeding were also evaluated. RESULTS: Under baseline conditions isoflurane anesthesia resulted in deterioration of respiratory parameters (arterial pCO2 and pO2) and increased brain water content. After SAH, isoflurane and chloral hydrate were associated with reduced MAP, incomplete recovery of post-hemorrhagic rCBF (23 ± 13% and 87 ± 18% of baseline, respectively) and a high anesthesia-related mortality (17 and 50%, respectively). Anesthesia with MMF provided stable hemodynamics (MAP between 100-110 mmHg), high post-hemorrhagic rCBF values, and a high rate of re-bleedings (> 50%), a phenomenon often observed after SAH in humans. CONCLUSION: Based on these findings we recommend anesthesia with MMF for the endovascular perforation model of SAH.