Urinary Excretion of Inorganic and Organic Fluoride after Inhalation of Sevoflurane

This study was designed to investigate the defluorination of sevoflurane in patients. Five patients, scheduled for orthopedic surgery, were administered sevoflurane for 60 min during NLA-nitrous oxide-oxygen. The end-tidal concentration of sevoflurane was adjusted at 0.6% throughout the entire inhalation period. The serum concentration of inorganic F- increased significantly 15 min after the onset of inhalation and reached a plateau at 45 min with a mean value about 15 μM. The serum organic fluoride level increased significantly 45 min after the onset of inhalation and did not change significantly 4 hr later with a mean value of about 140 μM. The elimination half-lives and rate constants were calculated from urinary data to be 2040 min and 0.00034 for inorganic fluoride and 1800 min and 0.00038 for organic fluoride respectively. The ratio organic/inorganic fluoride was calculated to be 2.3.This study was supported in part by a Grant-in-aid for Science Research from the Ministry of Education, Science and Culture of Japan

Clinical Evaluation and Metabolism of Sevoflurane in Patients

Sevoflurane was submitted to Phase II studies in patients following Phase I studies. Sevoflurane, 2% inspired during maintenance, was administered with 50% N2O in oxygen to produce surgical anesthesia in 9 orthopedic patients of ASA Physical Status I. Under controlled ventilation, endotracheal concentration of sevoflurane was recorded. The blood concentration of sevoflurane was measured during and after the inhalation. Serum, urinary inorganic fluoride, and glucuronide of hexafluoroisopropanol were analysed with ion chromatographic analyzer. The patient inhaled sevoflurane for 3.5 ± 1.6 hr. All the patients were anesthetized and operated uneventfully. Postoperative laboratory findings showed no unexplainable abnormality. The end expiratory concentration of sevoflurane reached a plateau in 4.0 ± 0.8 min and fell rapidly after discontinuation of sevoflurane. Blood concentration of sevoflurane was about 500 μM during inhalation. It decreased promptly after termination of sevoflurane and was not correlated with anesthetic time. The time for verbal response after discontinuation was 11.8 ± 4.2 min. The serum concentration of inorganic fluoride increased after inhalation and reached a plateau (13.7 ± 8.2 μM) in 120 min. The level lasted for 120 min after anesthesia and fell by half at 12 hr after anesthesia. Urinary fluoride concentration varied from 20 to 3,000 μM during the first 12 hr urine, and showed its maximum in the first postoperative 12 or 24 hr urine. The findings that sevoflurane with nitrous oxide and oxygen produced surgical anesthesia without any sequelae and that the serum fluoride level did not exceed the nephrotoxic level warrent the further clinical evaluation in a wider range of subjects.A part of this work was supported by a Research Grant from the Japanese Ministry of Education, Science and Culture and presented at the 8th European Congress of Anaesthesiology, Vienna, Austria, in September, 1986