Understanding the mechanisms by which isoflurane modifies the hyperglycemic response to surgery

We studied the effect of anesthesia on the kinetics of perioperative glucos e metabolism by using stable isotope tracers. Twenty-three patients undergo ing cystoprostatectomy were randomly assigned to receive epidural analgesia combined with general anesthesia (n = 8), fentanyl and midazolam anesthesi a (n = 8), or inhaled anesthesia with isoflurane (n = 7). Whole-body glucos e production and glucose clearance were measured before and during surgery. Glucose clearance significantly decreased during surgery independent of th e type of anesthesia. Epidural analgesia caused a significant decrease in g lucose production from 10.2 +/- 0.4 to 9.0 +/- 0.4 mu mol.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 p roduction did not significantly change during fentanyl/midazolam anesthesia (before surgery, 10.5 +/- 0.5 mu mol.kg(-1).min(-1); during surgery, 10.1 +/- 0.5 mu mol.kg(-1).min(-1)), but plasma glucose concentration significan tly 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 g lucose concentration (from 5.2 +/- 0.1 mmol/L to 7.2 +/- 0.5 mmol/L) and gl ucose production (from 10.8 +/- 0.5 mu mol.kg(-1).min(-1) to 12.4 +/- 1.0 m u mol.kg(-1).min(-1)) (P < 0.05). Epidural analgesia prevented the hypergly cemic response to surgery by a decrease in glucose production. The increase d glucose plasma concentration during fentanyl/midazolam anesthesia was cau sed by a decrease in whole-body glucose clearance. The hyperglycemic respon se observed during isoflurane anesthesia was a consequence of both impaired glucose clearance and increased glucose production.