Abstract

The disposition of enflurane, a volatile halogenated anesthetic, was studied in obese (n = 26) and nonobese (n = 8) consenting adult subjects undergoing elective intra-abdominal surgical procedures. Enflurane and fluoride ion, a nephrotoxic metabolite of enflurane, were measured in the blood of subjects before, during and up to 24 hr after exposure to pharmacologically equivalent doses of enflurane [approximately 2.0 MAC hr (the minimal alveolar concentration at which 50% of humans do not respond to a painful stimulus)] Arterial enflurane in obese subjects reached maximal concentrations 3 times faster than nonobese subjects who reached similar blood levels 80 min after the initiation of anesthesia. The blood/gas partition coefficient for enflurane in the obese was found to be 30% lower than that in the nonobese (0.99 +/- 0.02 vs. 1.42 +/- 0.02) and may possibly explain the observed differences in enflurane uptake. The rate at which inorganic fluoride appeared in obese serum (5.5 microM/hr) was twice that seen in the nonobese group. No differences in urinary fluoride excretion were demonstrated. Maximum serum fluoride concentration occurred 2 hr postenflurane anesthesia in both groups with the obese having a 60% higher concentration (27.8 +/- 2.0 vs. 17.0 +/- 3.0 microM), indicating increased biotransformation in the obese. Hepatic triglyceride content was demonstrated to be unrelated to the increased enflurane biotransformation observed in obese subjects. Equations are presented for the estimation of mean maximum serum inorganic fluoride levels in both obese and nonobese subjects after enflurane anesthesia.