title: Long-duration low-flow sevoflurane and isoflurane effects on postoperative renal and hepatic function.
abstract: Sevoflurane degradation by carbon dioxide absorbents during low-flow anesthesia forms the haloalkene Compound A, which causes nephrotoxicity in rats. Numerous studies have shown no effects of Compound A formation on postoperative renal function after moderate-duration (3-4 h) low-flow sevoflurane; however, effects of longer exposures remain unresolved. We compared renal function after long-duration low-flow (<1 L/min) sevoflurane and isoflurane anesthesia in consenting surgical patients with normal renal function. To maximize degradant exposure, Baralyme was used, and anesthetic concentrations were maximized (no nitrous oxide and minimal opioids). Inspired and expired Compound A concentrations were quantified. Blood and urine were obtained for laboratory evaluation. Sevoflurane (n = 28) and isoflurane (n = 27) groups were similar with respect to age, sex, weight, ASA status, and anesthetic duration (9.1 +/- 3.0 and 8.2 +/- 3.0 h, mean +/- SD) and exposure (9.2 +/- 3.6 and 9.1 +/- 3.7 minimum alveolar anesthetic concentration hours). Maximum inspired Compound A was 25 +/- 9 ppm (range, 6-49 ppm), and exposure (area under the concentration-time curve) was 165 +/- 95 (35-428) ppm. h. There was no significant difference between anesthetic groups in 24- or 72-h serum creatinine, blood urea nitrogen, creatinine clearance, or 0- to 24-h or 48- to 72-h urinary protein or glucose excretion. Proteinuria and glucosuria were common in both groups. There was no correlation between Compound A exposure and any renal function measure. There was no difference between anesthetic groups in 24- or 72-h aspartate aminotransferase or alanine aminotransferase. These results show that the renal and hepatic effects of long-duration low-flow sevoflurane and isoflurane were similar. No evidence for low-flow sevoflurane nephrotoxicity was observed, even at high Compound A exposures as long as 17 h. Proteinuria and glucosuria were common and nonspecific postoperative findings. Long-duration low-flow sevoflurane seems as safe as long-duration low-flow isoflurane anesthesia.
  
  
  CONCLUSIONS
  Postoperative renal function after long-duration low-flow sevoflurane (with Compound A exposures greater than those typically reported) and isoflurane anesthesia were not different, as assessed by serum creatinine, blood urea nitrogen, and urinary excretion of protein and glucose. This suggests that low-flow sevoflurane is as safe as low-flow isoflurane, even at long exposures.
authors.affiliation: Department of Anesthesiology, University of Washington, Seattle, Washington 98195, USA. kharasch@u.washington.edu
authors.forename: E D
authors.initials: ED
authors.lastname: Kharasch
authors.forename: E J
authors.initials: EJ
authors.lastname: Frink
authors.forename: A
authors.initials: A
authors.lastname: Artru
authors.forename: P
authors.initials: P
authors.lastname: Michalowski
authors.forename: G A
authors.initials: GA
authors.lastname: Rooke
authors.forename: W
authors.initials: W
authors.lastname: Nogami
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000410:Alanine Transaminase / Q000097:blood; D018685:Anesthetics, Inhalation / Q000008:administration & dosage* / Q000032:analysis; D001219:Aspartate Aminotransferases / Q000097:blood; D001944:Breath Tests; D004987:Ethers / Q000032:analysis; D005260:Female; D005459:Fluorides / Q000097:blood; D006801:Humans; D006845:Hydrocarbons, Fluorinated / Q000032:analysis; D007530:Isoflurane / Q000008:administration & dosage*; D007668:Kidney / Q000187:drug effects* / Q000502:physiology; D008099:Liver / Q000187:drug effects* / Q000502:physiology; D008297:Male; D008738:Methyl Ethers / Q000008:administration & dosage*; D008875:Middle Aged; D000077149:Sevoflurane; D013997:Time Factors
chemical_list: D018685:Anesthetics, Inhalation; D004987:Ethers; D006845:Hydrocarbons, Fluorinated; D008738:Methyl Ethers; D000077149:Sevoflurane; C078742:fluoromethyl 2,2-difluoro-1-(trifluoromethyl)vinyl ether; D007530:Isoflurane; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D005459:Fluorides