Assessment of low-flow sevoflurane and isoflurane effects on renal function using sensitive markers of tubular toxicity

Carbon dioxide absorbents degrade sevoflurane, particularly at low gas flow rates, to fluoromethyl-2,2-difluoro-1-(trifluoromethyl)vinyl ether (compound A). Compound A causes renal proximal tubular injury in rats but has had no effect on blood urea nitrogen (BUN) or creatinine concentrations in pati...

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Published in:Anesthesiology (Philadelphia) 1997-06, Vol.86 (6), p.1238-1253
Main Authors: KHARASCH, E. D, FRINK, E. J, ZAGER, R, BOWDLE, T. A, ARTRU, A, NOGAMI, W. M
Format: Article
Language:English
Subjects:
Acetylglucosaminidase - urine
Adult
Aged
Alanine Transaminase - blood
Anesthesia, General - adverse effects
Anesthesia, General - methods
Anesthetics, Inhalation - administration & dosage
Anesthetics, Inhalation - adverse effects
Anesthetics, Inhalation - metabolism
Aspartate Aminotransferases - blood
Biological and medical sciences
Biomarkers - analysis
Blood Urea Nitrogen
Creatinine - blood
Drug toxicity and drugs side effects treatment
Ethers - administration & dosage
Ethers - adverse effects
Ethers - metabolism
Female
Fluorides - blood
Glutathione Transferase - urine
Humans
Hydrocarbons, Fluorinated - adverse effects
Hydrocarbons, Fluorinated - metabolism
Isoflurane - administration & dosage
Isoflurane - adverse effects
Kidney - drug effects
Kidney - physiology
Kidney Tubular Necrosis, Acute - chemically induced
Kidney Tubular Necrosis, Acute - enzymology
Kidney Tubular Necrosis, Acute - metabolism
L-Lactate Dehydrogenase - blood
Liver - drug effects
Liver - physiology
Male
Medical sciences
Methyl Ethers
Middle Aged
Pharmacology. Drug treatments
Sevoflurane
Toxicity: urogenital system
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Summary:Carbon dioxide absorbents degrade sevoflurane, particularly at low gas flow rates, to fluoromethyl-2,2-difluoro-1-(trifluoromethyl)vinyl ether (compound A). Compound A causes renal proximal tubular injury in rats but has had no effect on blood urea nitrogen (BUN) or creatinine concentrations in patients. This investigation compared the effects of low-flow sevoflurane and isoflurane on renal tubular function in surgical patients using conventional (BUN and creatinine) and finer indices of renal injury, specifically those biomarkers sensitive for compound A toxicity in rats (glucosuria, proteinuria, and enzymuria [N-acetyl-beta-D-glucosaminidase (NAG) and alpha-glutathione-S-transferase (alpha GST)]). Consenting patients with normal preoperative renal function at two institutions were randomized to receive sevoflurane (n = 36) or isoflurane (n = 37) in oxygen and air. Total gas flow was 1 l/min, opioid doses were minimized, and barium hydroxide lime was used to maximize anesthetic degradation. Inspiratory and expiratory compound A concentrations were quantified every 30-60 min. Blood and urine were obtained before and 24-72 h after anesthesia for laboratory evaluation. Sevoflurane and isoflurane groups were similar with respect to age, weight, sex, American Society of Anesthesiologists status, anesthetic duration (3.7 or 3.9 h), and anesthetic exposure (3.6 or 3 minimum alveolar concentration [MAC]-hour). Maximum inspired compound A concentration (mean +/- standard deviation) was 27 +/- 13 ppm (range, 10-67 ppm). Areas under the inspired and expired compound A concentration versus time curves (AUC) were 79 +/- 54-ppm-h (range, 10-223 ppm-h) and 53 +/- 40 ppm-h (range, 6-159 ppm-h), respectively. There was no significant difference between anesthetic groups in postoperative serum creatinine or BUN, or urinary excretion of protein, glucose, NAG, proximal tubular alpha GST, or distal tubular pi GST. There was no significant correlation between compound A exposure (AUC) and protein, glucose, NAG, alpha GST, or pi GST excretion. Postoperative alanine and aspartate aminotransferase concentrations were not different between the anesthetic groups, and there were no significant correlations between compound A exposure and alanine or aspartate aminotransferase concentrations. The renal tubular and hepatic effects of low-flow sevoflurane and isoflurane were similar as assessed using both conventional measures of hepatic and renal function and more sensitive biochemical
ISSN:0003-3022
1528-1175
DOI:10.1097/00000542-199706000-00004