DOSE-RELATED BIOCHEMICAL MARKERS OF RENAL INJURY AFTER SEVOFLURANE VERSUS DESFLURANE ANESTHESIA IN VOLUNTEERS

Sevoflurane (CH2F-O-CH[CF3](2)) reacts with carbon dioxide absorbents to produce Compound A (CH2F-O-C[=CF2][CF3]). Because of concern about the potential nephrotoxicity of Compound A, the United States package label (but not that of several other countries) for sevoflurane recomm ends the use of fresh gas flow rates of 2 L/min or more. We previously demonstrated in humans that a 2-L/min flow rate delivery of 1.25 mini mum alveolar anesthetic concentration (MAC) sevoflurane for 8 h can in jure glomeruli (i.e., produce albuminuria) and proximal tubules (i.e., produce glucosuria and urinary excretion of alpha-glutathione-S-trans ferase [alpha-GST]). The present report extends this investigation to fasting volunteers given 4 h (n = 9) or 2 h (n = 7) of 1.25 MAC sevofl urane versus desflurane at 2 L/min via a standard circle absorber anes thetic system (all subjects given both anesthetics). Markers of renal injury (urinary creatinine, albumin, glucose, alpha-GST, and blood ure a nitrogen) did not reveal significant injury after anesthesia with de sflurane. Sevoflurane degradation with a 2-L/min fresh gas inflow rate produced average inspired concentrations of Compound A of 40 +/- 4 pp m (mean +/- SD, 8-h exposure [data from previous study]), 42 +/- 2 ppm (4 h), and 40 +/- 5 ppm (2 h). Relative to desflurane, sevoflurane gi ven for 4 h caused statistically significant transient injury to glome ruli (slightly increased urinary albumin and serum creatinine) and to proximal tubules (increased urinary alpha-GST). Other measures of inju ry did not differ significantly between anesthetics. Neither anestheti c given for 2 h at 1.25 MAC produced injury. We conclude that 1.25 MAC sevoflurane plus Compound A produces dose-related glomerular and tubu lar injury with a threshold between 80 and 168 ppm/h of exposure to Co mpound A. This threshold for renal injury in normal humans approximate s that found previously in normal rats. Implications: Human (and rat) kidneys are injured by a reactive compound (Compound A) produced by de gradation of the clinical inhaled anesthetic, sevoflurane. Injury incr eases with increasing duration of exposure to a given concentration of Compound A. The response to Compound A has several implications, as d iscussed in the article.