Ed. Kharasch et al., ASSESSMENT OF LOW-FLOW SEVOFLURANE AND ISOFLURANE EFFECTS ON RENAL-FUNCTION USING SENSITIVE MARKERS OF TUBULAR TOXICITY, Anesthesiology, 86(6), 1997, pp. 1238-1253
Background: Carbon dioxide absorbents degrade sevoflurane, particularl
y at low gas flow rates, to fluoromethyl-2,2-difluoro-1-(trifluorometh
yl)vinyl ether (compound A). Compound A causes renal proximal tubular
injury in rats but has had no effect on blood urea nitrogen (BUN) or c
reatinine concentrations in patients, This investigation compared the
effects of low-flow sevoflurane and isoflurane on renal tubular functi
on in surgical patients using conventional (BUN and creatinine) and fi
ner indices of renal injury, specifically those biomarkers sensitive f
or compound A toxicity in rats (glucosuria, proteinuria, and enzymuria
[N-acetyl-beta-D-glucosaminidase (NAG) and alpha-glutathione-S-transfe
rase (alpha GST)]). Methods: Consenting patients with normal preoperat
ive renal function at two institutions were randomized to receive sevo
flurane (n = 36) or isoflurane (n = 37) in oxygen and air. Total gas n
ow was 1 l/min, opioid doses were minimized, and barlum hydroxide lime
was used to maximize anesthetic degradation Inspiratory and expirator
y compound A concentrations were quantified every 30-60 min, Blood and
urine were obtained before and 24-72 h after anesthesia for laborator
y evaluation. Results: Sevoflurane and isoflurane groups were similar
with respect to age, weight, sex, American Society of Anesthesiologist
s 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 p
pm (range, 10-67 ppm). Areas under the inspired and expired compound A
concentration versus time curves (AUC) were 79 +/- 54-ppm-h (range, 1
0-223]ppm-h) and 53 +/- 40 ppm-h (range, 6-159 ppm-h), respectively. T
here was no significant difference between anesthetic groups in postop
erative serum creatinine or BUN, or urinary excretion of protein, gluc
ose, NAG, proximal tubular alpha GST, or distal tubular pi GST. There
was no significant correlation between compound A exposure (AUC) and p
rotein, glucose, NAG, alpha GST, or pi GST excretion. Postoperative al
anine and aspartate aminotransferase concentrations were nor different
between the anesthetic groups, and there were no significant correlat
ions between compound A exposure and alanine or aspartate aminotransfe
rase concentrations. Conclusions: The renal tubular and hepatic effect
s of low-flow sevoflurane and isoflurane were similar as assessed usin
g both conventional measures of hepatic and renal function and more se
nsitive biochemical markers of renal tubular cell necrosis, Moderate d
uration low-flow sevoflurane anesthesia, during which compound A forma
tion occurs, appears to be as safe as low-flow isoflurane anesthesia.