Chronic cocaine administration reversibly increases isoflurane minimum alveolar concentration in sheep.
BACKGROUND
Significant numbers of patients are seen for surgery and anesthesia with a history of chronic cocaine use. However, little is known about how cocaine use influences anesthetic physiology and pharmacology. The purpose of this study was to investigate the effect of chronic cocaine exposure on the minimum alveolar concentration (MAC) of isoflurane in sheep.


METHODS
Isoflurane MAC was determined at baseline in 12 sheep using a standard protocol. The animals were subsequently exposed to cocaine for 18 days. Cocaine exposure consisted of a continuous subcutaneous cocaine infusion at 0.2 mg.kg-1.h-1, twice daily 4-mg/kg intravenous boluses and repeated hourly 4 mg/kg cocaine boluses for 8 h on day 18. Minimum alveolar concentration determinations were repeated again on days 15, 18, and on day 28 after 10 days of cocaine abstinence.


RESULTS
Compared to baseline MAC (1.53 +/- 0.12%) cocaine exposure significantly increased isoflurane MAC on days 15 (1.91 +/- 0.14%) and 18 (1.78 +/- 0.13%; P = .005). MAC decreased after discontinuation of cocaine and was not different from baseline on day 28 (1.67 +/- 0.11).


CONCLUSIONS
In sheep, chronic cocaine exposure resulted in a reversible increase in isoflurane MAC. This finding contrasts with studies of other central nervous system stimulants, which have demonstrated a decrease in MAC after chronic drug exposure.
Bernards
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CM
Department of Anesthesiology, University of Washington School of Medicine, Seattle 98195-6540, USA. chrisb@u.washington.edu
Kern
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Cullen
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D018685:Anesthetics, Inhalation / Q000493:pharmacokinetics*; D000818:Animals; D003042:Cocaine / Q000097:blood / Q000494:pharmacology*; D004347:Drug Interactions; D007530:Isoflurane / Q000493:pharmacokinetics*; D008297:Male; D011650:Pulmonary Alveoli / Q000378:metabolism*; D012756:Sheep
D018685:Anesthetics, Inhalation; D007530:Isoflurane; D003042:Cocaine