DIFFERENTIAL EFFECTS OF ANESTHETIC AGENTS ON OUTCOME FROM NEAR-COMPLETE BUT NOT INCOMPLETE GLOBAL ISCHEMIA IN THE RAT

Abstract

S356 Anesthetic agents are believed to reduce cerebral metabolic rate (CMR) due to reduction in electroencephalographic (EEG) activity. It has been postulated that anesthetic agents which reduce CMR will only protect the brain against ischemia insufficiently severe to abolish the EEG and provide no protection when ischemia is severe enough to cause isoelectricity. Although biochemical evidence has been provided to support this principle (1), no outcome studies have addressed this issue. This study was designed to determine if differential anesthetic effects on outcome from global cerebral ischemia are present during ischemia when the EEG remains active or when the EEG is allowed to become isoelectric. Methods: Fasted rats were subjected to either 1) incomplete ischemia (attenuated EEG; 20 min of MAP = 50 mmHg and bilateral carotid occlusion); or 2) near-complete ischemia (isoelectric EEG; 10 min of MAP = 30 mmHg and bilateral carotid occlusion) while anesthetized with isoflurane (1.4%), ketamine (1mg/kg/min), or 70% N2O and fentanyl (25[micro sign]g/kg/hr). Brain temperature was controlled during and for 24 hrs post-ischemia (37.5 +/- 0.1 [degree sign]C). Five days after ischemia, hippocampal CA1 injury was measured. Percentages of dead neurons were compared amongst anesthetic groups by ANOVA followed by Tukey's post-hoc comparison method. Values = mean +/- s.d. Results: We did not detect a difference in CA1 neuronal death among anesthetic agents during incomplete ischemia (P = 0.22; fentanyl 38% +/- 20%, isoflurane 31% +/- 10%, ketamine 43% +/- 22%). During near-complete ischemia, a difference was present among anesthetic agents (P = 0.00008; fentanyl 88% +/- 9%; isoflurane 37% +/- 20%, ketamine 70% +/- 28%). By post hoc analysis, isoflurane was protective relative to fentanyl (P=0.00007) and ketamine (P=0.0061). We did not detect a significant difference between fentanyl and ketamine (P=0.143). Conclusions: Given rigorous physiologic control, outcome from near-complete but not incomplete cerebral ischemia was dependent upon the anesthetic agent administered during the ischemic insult. Exploration of the mechanistic basis for the differential effects of anesthetic agents on outcome from near-complete ischemia is warranted. (Figure 1)Figure 1: Circles depict % dead neurons in hippocampal CA1 determined 5 days after either near-complete (isoelectric EEG; LEFT) or incomplete (attenuated EEG; RIGHT) forebrain ischemia. Horizontal bars depict mean values. Isoflurane (I) caused reduced damage after near-complete ischemia when compared to either ketamine (K) or fentanyl/N2O (F). There was no effect for anesthetic on histologic outcome from incomplete ischemia.