Dose of compound A, not sevoflurane, determines changes in the biochemical markers of renal injury in healthy volunteers.

UNLABELLED: Administration of sevoflurane in a circle absorption system generates Compound A, a nephrotoxin in rats. Reports examining the potential of Compound A to produce renal injury in humans have provided conflicting results. We tested the possibility that there is a threshold to Compound A-induced renal injury in humans and that, above this threshold, renal injury increases with increasing doses of Compound A. Eleven volunteers received 3% sevoflurane for 8 h at 2 L/min, and three volunteers received 3% sevoflurane for 8 h at 4-6 L/min. We measured inspired and expired concentrations of Compound A and urinary excretion of albumin, alpha-glutathione-S-transferase (GST), and glucose. The median urinary excretion of albumin, glucose, and alpha-GST for the first 3 days after anesthesia increased significantly from preanesthetic values in the 2-L/min group. Compound A doses < 240 ppm-h resulted in normal urinary excretion of albumin, glucose, and alpha-GST. Five of seven subjects who received doses > 240 ppm-h had abnormal excretion of albumin, and six of seven had abnormal alpha-GST urinary excretion (P < 0.05). Urinary excretion of albumin, alpha-GST, and glucose was normal by 14 days after exposure. We conclude that sevoflurane administration for 8 h at 2 L/min results in albuminuria and enzymuria when the dose of Compound A exceeds 240 ppm-h. That is, a Compound A concentration of 30 ppm breathed for > or = 8 h may produce transient renal injury.

IMPLICATIONS: We examined the dose-response relationship of sevoflurane/Compound A and urinary excretion of albumin, glucose, and alpha-GST. Sevoflurane exposure for 8 h at a 2-L/min inflow rate produces transient albuminuria and enzymuria in healthy volunteers when the dose of Compound A exceeds 240 ppm-h (30 ppm for 8 h).