Pharmacokinetic Study on Excretion of Inorganic Fluoride Ion, a Metabolite of Sevoflurane

Blood and urinary inorganic fluoride ion concentration was determined in six healthy volunteers after inhalation of 2% sevoflurane for one hour. The serum inorganic fluoride ion concentration increased 30 min after discontinuation of inhalation to 14.8 ± 3.0 μmol/liter, which was about 10 times higher than the level before inhalation. The serum elimination constant of inorganic fluoride was calculated to be 0.000467 and the half-life was 1,487 min. The urinary excretion rate of inorganic fluoride ion was the highest ( 452 nmol/min) after 12-24 hr. The urinary excretion rate constant of inorganic fluoride was calculated to be 0.000268 and the half-life was 2,583 min. The distribution volume of inorganic fluoride excreted in the urine was calculated to be 127 liters. This value showed that fluoride ion produced in the cell cannot readily pass through the cell membrane due to its polarity, resulting in a delay of the maximum excretion rate of inorganic fluoride until the first or second day after inhalation of the anesthetic.This study was supported in part by a Grant-in-aid for Science Research from the Ministry of Education, Science and Culture of Japan and a Grant-in-aid from the Association for the Advancement of Medicine of the Tsuchiya Foundation

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

Risk factors associated with late aneurysmal sac expansion after endovascular abdominal aortic aneurysm repair

PURPOSEWe aimed to identify the risk factors associated with late aneurysmal sac expansion after endovascular abdominal aortic aneurysm repair (EVAR).METHODSWe retrospectively reviewed contrast-enhanced computed tomography (CT) images of 143 patients who were followed for ≥6 months after EVAR. Sac expansion was defined as an increase in sac diameter of 5 mm relative to the preoperative diameter. Univariate and multivariate analyses were performed to identify associated risk factors for late sac expansion after EVAR from the following variables: age, gender, device, endoleak, antiplatelet therapy, internal iliac artery embolization, and preprocedural variables (aneurysm diameter, proximal neck diameter, proximal neck length, suprarenal neck angulation, and infrarenal neck angulation).RESULTSUnivariate analysis revealed female gender, endoleak, aneurysm diameter ≥60 mm, suprarenal neck angulation >45°, and infrarenal neck angulation >60° as factors associated with sac expansion. Multivariate analysis revealed endoleak, aneurysm diameter ≥60 mm, and infrarenal neck angulation >60° as independent predictors of sac expansion (P < 0.05, for all).CONCLUSIONOur results suggest that patients with small abdominal aortic aneurysms (<60 mm) and infrarenal neck angulation ≤60° are more favorable candidates for EVAR. Intraprocedural treatments, such as prophylactic embolization of aortic branches or intrasac embolization, may reduce the risk of sac expansion in patients with larger abdominal aortic aneurysms or greater infrarenal neck angulation

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