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ANESTHETIC PHARMACOLOGY

Understanding the Mechanisms by Which Isoflurane Modifies the Hyperglycemic Response to Surgery

Ralph Lattermann, MD^*, Thomas Schricker, MD, PhD^*, Ulrich Wachter, Michael Georgieff, MD, PhD, and Axel Goertz, MD, PhD

*Department of Anesthesia, McGill University, Montreal, Quebec, Canada; Clinic of Anesthesiology, University of Ulm, Ulm, Germany; and Department of Anesthesia, St. Marien-Krankenhaus, Ludwigshafen, Germany

Address correspondence and reprint requests to Dr. Thomas Schricker, Department of Anesthesia, McGill University, Royal Victoria Hospital, Room S5.05, 687 Pine Ave. W., Montreal, Quebec, Canada H3A 1A1.

We studied the effect of anesthesia on the kinetics of perioperative glucose metabolism by using stable isotope tracers. Twenty-three patients undergoing cystoprostatectomy were randomly assigned to receive epidural analgesia combined with general anesthesia (n = 8), fentanyl and midazolam anesthesia (n = 8), or inhaled anesthesia with isoflurane (n = 7). Whole-body glucose production and glucose clearance were measured before and during surgery. Glucose clearance significantly decreased during surgery independent of the type of anesthesia. Epidural analgesia caused a significant decrease in glucose production from 10.2 ± 0.4 to 9.0 ± 0.4 µmol · kg^-1 · min^-1 (P < 0.05), whereas the plasma glucose concentration was not altered (before surgery, 5.0 ± 0.2 mmol/L; during surgery, 5.2 ± 0.1 mmol/L). Glucose production did not significantly change during fentanyl/midazolam anesthesia (before surgery, 10.5 ± 0.5 µmol · kg^-1 · min^-1; during surgery, 10.1 ± 0.5 µmol · kg^-1 · min^-1), but plasma glucose concentration significantly increased from 4.8 ± 0.1 mmol/L to 5.3 ± 0.2 mmol/L during surgery (P < 0.05). Isoflurane anesthesia caused a significant increase in plasma glucose concentration (from 5.2 ± 0.1 mmol/L to 7.2 ± 0.5 mmol/L) and glucose production (from 10.8 ± 0.5 µmol · kg^-1 · min^-1 to 12.4 ± 1.0 µmol · kg^-1 · min^-1) (P < 0.05). Epidural analgesia prevented the hyperglycemic response to surgery by a decrease in glucose production. The increased glucose plasma concentration during fentanyl/midazolam anesthesia was caused by a decrease in whole-body glucose clearance. The hyperglycemic response observed during isoflurane anesthesia was a consequence of both impaired glucose clearance and increased glucose production.

Implications: Epidural analgesia combined with general anesthesia prevented thehyperglycemic response to surgery by decreasing endogenous glucose production.The increased glucose plasma concentration in patients receivingfentanyl/midazolam anesthesia was caused by a decrease in whole-body glucoseclearance. The hyperglycemic response observed during inhaled anesthesia withisoflurane was a consequence of both impaired glucose clearance and increasedglucose production.

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