Nephrotoxicity of Sevoflurane Versus Desflurane Anesthesia in Volunteers

Abstract

Present package labeling for sevoflurane recommends the use of fresh gas flow rates of 2 L/min or more when delivering anesthesia with sevoflurane. This recommendation resulted from a concern about the potential nephrotoxicity of a degradation product of sevoflurane, "Compound A," produced by the action of carbon dioxide absorbents on sevoflurane. To assess the adequacy of this recommendation, we compared the nephrotoxicity of 8 h of 1.25 minimum alveolar anesthetic concentration (MAC) sevoflurane (n = 10) versus desflurane (n = 9) in fluid-restricted (i.e., nothing by mouth overnight) volunteers when the anesthetic was given in a standard circle absorber anesthetic system at 2 L/min. Subjects were tested for markers of renal injury (urinary albumin, glucose, alpha-glutathione-S-transferase [GST], and pi-GST; and serum creatinine and blood urea nitrogen [BUN]) before and 1, 2, 3, and/or 5-7 days after anesthesia. Desflurane did not produce renal injury. Rebreathing of sevoflurane produced average inspired concentrations of Compound A of 41 +/- 3 ppm (mean +/- SD). Sevoflurane was associated with transient injury to: 1) the glomerulus, as revealed by postanesthetic albuminuria; 2) the proximal tubule, as revealed by postanesthetic glucosuria and increased urinary alpha-GST; and 3) the distal tubule, as revealed by postanesthetic increased urinary pi-GST. These effects varied greatly (e.g., on postanesthesia Day 3, the 24-h albumin excretion was < 0.03 g (normal) for one volunteer; 0.03-1 g for five others; 1-2 g for two others; 2.1 g for one volunteer; and 4.4 g for another volunteer). Neither anesthetic affected serum creatinine or BUN, nor changed the ability of the kidney to concentrate urine in response to vasopressin, 5 U/70 kg subcutaneously (i.e., these measures failed to reveal the injury produced). In addition, sevoflurane, but not desflurane, caused small postanesthetic increases in serum alanine aminotransferase (ALT), suggesting mild, transient hepatic injury.

Efeitos do halotano, isoflurano e sevoflurano sobre a função renal em cães sob pinçamento aórtico infra-renal

“…So, it seems to have no nefrotoxic effects in men 19 . Some authors have recently observed that sevoflurane in low fresh gases flow may determine renal changes, characterized by increased albumin and glucose urinary excretion, as well as of some tubular enzymes 20,21 . These results, however, have been questioned by other authors 14,22,23 for believing that the best renal changes markers are still plasma urea and creatinine levels, and for the inexistence of significant evidences to credit tubular enzyme changes as major indicators of sevoflurane-induced renal injury.…”

“…Mais recentemente, alguns autores verificaram que o sevoflurano, quando empregado em baixo fluxo de gases frescos, pode determinar alterações renais, caracterizadas por aumento da excreção urinária de albumina e glicose, e de algumas enzimas tubulares 20,21 . No entanto, esses resultados têm sido questionados por outros autores 14,22,23 por acreditarem que os melhores marcadores de alterações renais ainda continuam a ser os níveis plasmáticos de uréia e creatinina e por não existirem evidências significativas para se creditarem às alterações enzimáticas tubulares uma indicação importante de ocorrência de lesão renal com o sevoflurano.…”

Nephrotoxicity of Halogenated Inhalational Anaesthetics: Fictions and Facts

“…However, attempts by other authors to copy the results of these studies failed. Frink et al [27] while using the same experimental protocol and the same laboratory tests were unable to duplicate the type of injury reported by Eger et al [28,29] There is no good explanation for the puzzling results obtained in one single lab. It must not be forgotten that even prolonged (610 h) sevoflurane (high or low fresh gas flow) or isoflurane anaesthesia increased urinary excre- tion of glucose, albumin, protein, and N-acetyl-ß-D-glucosaminidase to the same extent.…”

“…They reported post-anaesthetic albuminuria indicating injury of the glomerulus, glucosuria and increased urinary ·-GST as signs of proximal tubular injury, and increased urinary -GST indicating distal tubular injury. However, serum routine parameters of renal function such as creatinine, blood urea nitrogen or the ability to concentrate urine (vasopressin test) remained unchanged [28].…”

Glutathione S-transferases as biomarkers of organ damage: applications of rodent and canine GST enzyme immunoassays

“…A number of different groups have been able to identify specific damage to the proximal or distal tubules in the kidney by monitoring urinary GST. One study looked at kidney damage resulting from the administration of the anaesthetic sevoflurane [7]. The authors were able to distinguish between proximal and distal tubular damage by the simultaneous analysis of urinary h and yGST.…”