TY - JOUR
T1 - Assessment of low-flow sevoflurane and isoflurane effects on renal function using sensitive markers of tubular toxicity
AU - Kharasch, Evan D.
AU - Frink, Edward J.
AU - Zager, Richard
AU - Bowdle, T. Andrew
AU - Artru, Alan
AU - Nogami, Wallace M.
PY - 1997
Y1 - 1997
N2 - Background: 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 biomakers sensitive for compound A toxicity in rats (glucosuria, proteinuria, and enzymuria [N-acetyl-β-D-glucosaminidase (NAG) and α-glutathione-S-transferase (αGST)]). Methods: 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. Results: 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 αGST, or distal tubular ΠGST. There was no significant correlation between compound A exposure (AUC) and protein, glucose, NAG, αGST, or ΠGST 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. Conclusions: 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 markers of renal tubular cell necrosis. Moderate duration low-flow sevoflurane anesthesia, during which compound A formation occurs, appears to be as safe as low-flow isoflurane anesthesia.
AB - Background: 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 biomakers sensitive for compound A toxicity in rats (glucosuria, proteinuria, and enzymuria [N-acetyl-β-D-glucosaminidase (NAG) and α-glutathione-S-transferase (αGST)]). Methods: 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. Results: 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 αGST, or distal tubular ΠGST. There was no significant correlation between compound A exposure (AUC) and protein, glucose, NAG, αGST, or ΠGST 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. Conclusions: 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 markers of renal tubular cell necrosis. Moderate duration low-flow sevoflurane anesthesia, during which compound A formation occurs, appears to be as safe as low-flow isoflurane anesthesia.
KW - Anesthesia, low-flow
KW - Anesthetics, volatile: isoflurane; sevoflurane
KW - Carbon dioxide, absorption: Baralyme
KW - Compilations, inhilation anesthesia
KW - Degradants: Compound A; PIFE
KW - Toxicity: Compound A; hepatic; renal
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U2 - 10.1097/00000542-199706000-00004
DO - 10.1097/00000542-199706000-00004
M3 - Article
C2 - 9197292
AN - SCOPUS:0031003789
VL - 86
SP - 1238
EP - 1253
JO - Anesthesiology
JF - Anesthesiology
SN - 0003-3022
IS - 6
ER -