Cardiovascular effects of sevoflurane compared with those of isoflurane in volunteers.

BACKGROUND: Sevoflurane is a new inhalational anesthetic with desirable clinical properties. In some clinical situations, an understanding of the detailed cardiovascular properties of an anesthetic is important, so the authors evaluated the hemodynamic effects of sevoflurane in healthy volunteers not undergoing surgery. METHODS: Twenty-one subjects were randomized to receive sevoflurane, isoflurane, or sevoflurane: 60% N2O. Anesthesia was induced and maintained by inhalation of the designated anesthetic. Hemodynamic measurements were performed before anesthesia, during controlled ventilation, during spontaneous ventilation, and again during controlled ventilation after 5.5 h of anesthesia. RESULTS: A few subjects became excessively hypotensive at high anesthetic concentrations (2.0 minimum alveolar concentration [MAC] sevoflurane, 1.5 and 2.0 MAC isoflurane), preventing data collection. Sevoflurane did not alter heart rate, but decreased mean arterial pressure and mean pulmonary artery pressure. Cardiac index decreased at 1.0 and 1.5 MAC, but in subjects with mean arterial pressure > or = 50 mmHg returned to baseline values at 2.0 MAC when systemic vascular resistance decreased. Sevoflurane did not alter echocardiographic indices of ventricular function, but did decrease an index of afterload. Sevoflurane caused a greater decrease in mean pulmonary artery pressure than did isoflurane, but the cardiovascular effects were otherwise similar. Administration of sevoflurane with 60% N2O, prolonged administration or spontaneous ventilation resulted in diminished cardiovascular depression. CONCLUSIONS: At 1.0 and 1.5 MAC, sevoflurane was well tolerated by healthy volunteers. At 2.0 MAC, in subjects with mean arterial pressure > or = 50 mmHg, no adverse cardiovascular properties were noted. Similar to other contemporary anesthetics, sevoflurane caused evidence of myocardial depression. Hemodynamic instability was noted in some subjects at high anesthetic concentrations in the absence of surgical stimulation. The incidence was similar to that with isoflurane. The cardiovascular effects of sevoflurane were similar to those of isoflurane, an anesthetic commonly used in clinical practice since 1981.

Sevoflurane degradation product concentrations with soda lime during prolonged anesthesia.

STUDY OBJECTIVES: To evaluate the decomposition of sevoflurane in soda lime during prolonged sevoflurane anesthesia in humans. To evaluate for evidence of renal or hepatotoxicity as a result of exposure to these sevoflurane degradation compounds. DESIGN: Prospective evaluation in healthy volunteers. SETTING: Clinical research unit and postanesthesia care unit of a university hospital. PATIENTS: Six healthy male volunteers. INTERVENTIONS: Subjects were anesthetized with sevoflurane 1 to 1.2 minimum alveolar concentration for greater than 9 hours with a semiclosed circuit anesthetic technique (5-liter total flow) with fresh soda lime as the absorbent. MEASUREMENTS AND MAIN RESULTS: Laboratory tests of renal and hepatic function were performed before anesthesia and 1 and 5 days after anesthesia. During sevoflurane anesthesia, inhalation and exhalation circuit limb gas samples were obtained for degradation compound analysis. Only one degradation product, fluoromethyl-2,2-difluoro-1-(trifluoromethyl) vinyl ether (compound A), was detected. Inhalation concentration was maximal (7.6 +/- 1.0 ppm) at 2 hours and did not increase further after this time point. There were no differences in preanesthesia and postanesthesia tests of hepatic and renal function. CONCLUSIONS: Levels of the degradation compound (compound A) produced in semiclosed circuit sevoflurane anesthesia with soda lime are well below potential toxic levels and thus appear safe. When sevoflurane is administered under these conditions for prolonged anesthesia, concentrations of compound A do not continue to increase throughout anesthesia.

Renal concentrating function with prolonged sevoflurane or enflurane anesthesia in volunteers.

BACKGROUND: Sevoflurane, a new inhalational anesthetic, is biotransformed, producing peak plasma inorganic fluoride concentrations that may exceed 50 microM. We evaluated plasma inorganic fluoride concentrations with prolonged (> 9 MAC-h) sevoflurane or enflurane anesthesia in volunteers and compared renal concentrating function with desmopressin testing 1 and 5 days after anesthesia. METHODS: Fourteen healthy male volunteers received either enflurane or sevoflurane (1-1.2 MAC) for more than 9 MAC-h. Each volunteer was administered three tests of renal concentrating function, with intranasal desmopressin and urine collections performed 1 week before anesthesia and 1 and 5 days after anesthesia. Venous blood samples were obtained for plasma fluoride concentrations during and after anesthesia. Creatinine clearance was determined by 24-h urine collections 7 days before and 4 days after anesthesia. Urine samples were obtained before and 1, 2, and 5 days after anesthesia for determination of n-acetyl-beta-glucosaminidase and creatinine concentrations. RESULTS: Prolonged sevoflurane anesthesia (9.5 MAC-h) did not impair renal concentrating function on day 1 or 5 postanesthesia, as determined by desmopressin testing. Maximal urinary osmolality on day 1 postanesthesia was decreased (< 800 mOsm/kg) in two of seven enflurane-anesthetized volunteers; however, mean results did not differ from the those of the sevoflurane group. Mean peak plasma fluoride ion concentrations were 23 +/- 1 microM 6 h postanesthesia for enflurane and 47 +/- 3 microM at the end of anesthesia for sevoflurane (P < 0.01). There were no changes in creatinine clearance or urinary n-acetyl-beta-glucosaminidase concentration in either anesthetic group. DISCUSSION: Prolonged sevoflurane anesthesia did not impair renal concentrating function, as evaluated with desmopressin testing 1 and 5 days postanesthesia in healthy volunteers. Although with prolonged enflurane anesthesia, mean maximal osmolality values on day 1 postanesthesia did not differ from sevoflurane values, there was evidence in two volunteers at this time point of impairment in renal concentrating function, which normalized 5 days postanesthesia. These results occurred despite a higher peak plasma fluoride ion concentration and greater total inorganic fluoride renal exposure with sevoflurane anesthesia.