Whatever happened to sevoflurane?
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Anesthesia, Inhalation↗
Biomedical subjects
E J Frink
Publications and source records attributed to E J Frink.
The effects of sevoflurane, halothane, enflurane, and isoflurane on hepatic blood flow and oxygenation in chronically instrumented greyhound dogs.
Inhalational anesthetics produce differential effects on hepatic blood flow and oxygenation that may impact hepatocellular function and drug clearance. In this investigation, the effects of sevoflurane on hepatic blood flow and oxygenation were compared with those of enflurane, halothane, and isoflurane in ten chronically instrumented greyhound dogs. Each dog randomly received enflurane, halothane, isoflurane, and sevoflurane, each at 1.0, 1.5, and 2.0 MAC concentrations. Mean arterial blood pressure and cardiac output decreased in a dose-dependent fashion during all four anesthetics studied. Heart rate increased compared to control during enflurane, isoflurane, and sevoflurane anesthesia and did not change during halothane anesthesia. Hepatic arterial blood flow and portal venous blood flow were measured by chronically implanted electromagnetic flow probes. Hepatic O2 delivery and consumption were calculated after hepatic arterial, portal venous, and hepatic venous blood gas analysis. Hepatic arterial blood flow was maintained with sevoflurane and isoflurane. Halothane and enflurane reduced hepatic arterial blood flow during all anesthetic levels compared to control (P less than 0.05), with marked reductions occurring with 1.5 and 2.0 MAC halothane concomitant with an increase in hepatic arterial vascular resistance. Portal venous blood flow was reduced with isoflurane and sevoflurane at 1.5 and 2.0 MAC. A somewhat greater reduction in portal venous blood flow occurred during 2.0 MAC sevoflurane (P less than 0.05 compared to control and 1.0 MAC values for sevoflurane). Enflurane reduced portal venous blood flow at 1.0, 1.5, and 2.0 MAC compared to control. Halothane produced the greatest reduction in portal venous blood flow (P less than 0.05 compared to sevoflurane).(ABSTRACT TRUNCATED AT 250 WORDS)
Anesthetics↗
Quantification of the degradation products of sevoflurane in two CO2 absorbants during low-flow anesthesia in surgical patients.
Sevoflurane, a new inhalational anesthetic agent has been shown to produce degradation products upon interaction with CO2 absorbants. Quantification of these sevoflurane degradation products during low-flow or closed circuit anesthesia in patients has not been well evaluated. The production of sevoflurane degradation products was evaluated using a low-flow anesthetic technique in patients receiving sevoflurane anesthesia in excess of 3 h. Sevoflurane anesthesia was administered to 16 patients using a circle absorption system with O2 flow of 500 ml/min and average N2O flow of 273 ml/min. Preoperative and postoperative hepatic and renal function studies were performed. Gas samples were obtained from the inhalation and exhalation limbs of the anesthetic circuit for degradation product analysis and analyzed by gas chromatography/mass spectrometry for four degradation products. The first eight patients received sevoflurane anesthesia using soda lime, and the following eight patients received anesthesia using baralyme as the CO2 absorbant. CO2 absorbant temperatures were measured during anesthesia. Of the degradation products analyzed, only one compound [fluoromethyl-2, 2-difluoro-1-(trifluoromethyl) vinyl ether], designated compound A, was detectable. Concentrations of compound A increased during the first 4 h of anesthesia with soda lime and baralyme and declined between 4 and 5 h when baralyme was used. Mean maximum inhalation concentration of compound A using baralyme was 20.28 +/- 8.6 ppm (mean +/- SEM) compared to 8.16 +/- 2.67 ppm obtained with soda lime, a difference that did not reach statistical significance. A single patient achieved a maximal concentration of 60.78 ppm during low-flow anesthesia with baralyme. Exhalation concentrations of compound A were less than inhalation concentrations, suggesting patient uptake.(ABSTRACT TRUNCATED AT 250 WORDS)
Absorption↗
Systemic and regional hemodynamics of isoflurane and sevoflurane in rats.
The authors studied the effects of sevoflurane and isoflurane on systemic hemodynamics and regional blood flow distribution (microsphere technique) in 15 rats during general anesthesia with intravenous chloralose and controlled ventilation. Inhaled anesthetics were applied to reduce mean arterial blood pressure (MAP) to 70 mm Hg (1.66 vol% sevoflurane and 0.96 vol% isoflurane) and 50 mm Hg (MAP 50; 3.95 vol% sevoflurane and 2.43 vol% isoflurane). Control recordings were obtained with intravenous chloralose only. At a MAP of 70 mm Hg, both anesthetics reduced heart rate, cardiac output, and systemic vascular resistance to a similar degree. Isoflurane decreased systemic vascular resistance markedly at a MAP of 50 mm Hg and thereby maintained cardiac output at higher levels than sevoflurane. The left ventricular rate-pressure product decreased comparably with both anesthetics. Cerebral blood flow increased dose-dependently with both inhaled anesthetics but to a greater degree with isoflurane. Total hepatic blood flow remained unchanged from control at a MAP of 70 mm Hg but decreased at a MAP of 50 mm Hg. This was due to reductions of hepatic arterial and portal venous tributaries. Renal blood flow was reduced with only the high concentrations of the anesthetics. Myocardial blood flow was reduced at all concentrations of volatile anesthetic; however, the decrease was less with isoflurane. This would indicate a more pronounced coronary vasodilation by isoflurane as the rate-pressure product, as a measure of the actual left ventricular oxygen demand, decreased by comparable degrees with both anesthetics. Our results indicate that sevoflurane and isoflurane (each approximately 0.7 MAC) have no dissimilar systemic and regional hemodynamic effects at a MAP of 70 mm Hg in this animal model. At higher concentrations (approximately 1.7 MAC), cerebral blood flow was more with isoflurane than with sevoflurane and was associated with a more pronounced vasodilation in the myocardium.
Anesthesia, General↗
Plasma inorganic fluoride with sevoflurane anesthesia: correlation with indices of hepatic and renal function.
The biotransformation and plasma inorganic fluoride ion production of sevoflurane (the new volatile anesthetic) during and after surgical anesthesia was studied in 50 ASA I or II surgical patients. Twenty-five additional patients served as controls by receiving isoflurane. Sevoflurane or isoflurane was administered with a semiclosed (total gas flow, 2 L/min O2) circle absorption system for durations of 1.0 to greater than 7.0 minimal alveolar concentration (MAC) hours for surgical anesthesia (sevoflurane MAC, 2.05%; isoflurane MAC, 1.15%). Preoperative and postoperative blood urea nitrogen and creatinine concentrations were determined. Blood samples were obtained during and after anesthesia in both groups for determining anesthetic blood concentration analysis and plasma fluoride level. Plasma fluoride concentrations did not significantly increase during isoflurane anesthesia. Sevoflurane biotransformation produced a mean peak plasma inorganic fluoride concentration of 29.3 +/- 1.8 mumol/L, 2 h after anesthesia, which decreased to 18 mumol/L concentration by 8 h after anesthesia. The peak plasma inorganic fluoride ion concentration correlated with duration of sevoflurane anesthetic exposure. Five patients given sevoflurane had peak levels transiently exceeding 50 mumol/L, and one of these had a history of ingesting drugs potentially producing hepatic enzyme induction. No increases in postoperative levels of creatinine, blood urea nitrogen, direct bilirubin, or hepatic transaminase and no changes in serum electrolyte level occurred in either anesthetic group. Indirect bilirubin concentration increased significantly after sevoflurane anesthesia, but the increase was not of clinical significance (from 0.30 +/- 0.03 to 0.38 +/- 0.06 mg/dL). Indirect bilirubin concentrations did not increase after isoflurane anesthesia; the concentrations reached 0.31 +/- 0.04 mg/dL and did not differ significantly from those found with sevoflurane.(ABSTRACT TRUNCATED AT 250 WORDS)
Anesthesia, Inhalation↗
Clinical comparison of sevoflurane and isoflurane in healthy patients.
We compared blood pressure and heart rate changes in healthy patients during anesthesia with sevoflurane (n = 50) versus isoflurane (n = 25) and the rate of recovery after such anesthesia. After premedication with intravenous administration of midazolam, induction of anesthesia with thiopental, and intubation of the trachea facilitated with succinylcholine or vecuronium, anesthesia was maintained with approximately 1 MAC (sevoflurane, 2.05%; isoflurane, 1.15%) of the volatile anesthetic in oxygen for the duration of the operation. Anesthetic concentration was varied as indicated to maintain arterial blood pressure at +/- 20% of baseline values. Sevoflurane and isoflurane produced similar systolic and diastolic arterial blood pressures, but heart rate after incision was faster in patients given isoflurane. Recovery of response to command was shorter in patients given sevoflurane than that in patients given isoflurane (7.5 +/- 0.5 min versus 18.6 +/- 2.0 min). Consistent with this finding, venous blood drawn after anesthesia showed a more rapid initial decay with sevoflurane. Nausea and vomiting were comparable in both groups. We conclude that sevoflurane anesthesia, as compared with isoflurane, is associated with possible advantageous effects on heart rate and recovery.
Adult↗
Sevoflurane breakdown in soda lime.
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Absorption↗
Metabolism of sevoflurane.
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Anesthetics↗
Contributions of liver perfusion flow rate and enzyme inhibition to altered verapamil clearance with halothane: a study in the isolated perfused rat liver.
Verapamil clearance is reduced during halothane administration. This study evaluated relative contributions of reduced hepatic flow rate and hepatic metabolizing enzyme inhibition by halothane as a cause of reduced verapamil clearance. An isolated perfused rat liver model was utilized in which flow rate could be fixed during halothane administration. Perfusions were performed on five to six livers under each of the following conditions: (a) control--40 mL/min flow rate with no anesthetic exposure; (b) 1.5% halothane--40 mL/min; (c) 2.25% halothane--40 mL/min; (d) reduced flow--20 mL/min with no anesthetic exposure; and (e) reduced flow with 1.5% halothane--20 mL/min. Halothane caused dose-dependent decreases in both total hepatic and intrinsic clearance rates (P less than 0.05). With no anesthetic exposure, a flow reduction of 50% (20 mL/min) also gave a large reduction (P less than 0.05) in hepatic clearance of verapamil compared with the control condition (40 mL/min). The addition of 1.5% halothane to the reduced flow condition was not associated with further reduction in hepatic clearance rate. Results of this study suggest that although both reduced hepatic perfusion and hepatic enzymatic inhibition by halothane administration are associated with decreased verapamil clearance, a greater proportion of this decrease appears to be due to reductions in hepatic flow. The present results may apply to other drugs used in anesthesia that have high hepatic extraction ratios; thus, clearance of these drugs may be more dependent on hepatic blood flow than on hepatic enzyme activity.
Animals↗
Posterior arytenoid dislocation following uneventful endotracheal intubation and anesthesia.
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Anesthesia, Inhalation↗
Serum ammonia levels in response to glycine infusion in normal and cirrhotic rats.
Elevated serum ammonia may play a role in central nervous system derangement after transurethral resection of the prostate. Glycine used as a surgical irrigant for prostate resection produces ammonia as a by-product after liver and renal metabolism. The presence of liver dysfunction often leads to an inability to remove generated ammonia from the circulation. To determine whether the presence of cirrhosis allows significant metabolism of glycine and the resulting serum ammonia levels generated, the production of ammonia after glycine infusion was examined in normal and cirrhotic rats. Hepatic microsomal enzyme induction was produced in male Sprague-Dawley rats given sodium phenobarbital, added to the drinking water to hasten the development of cirrhosis, by increasing the toxicity of carbon tetrachloride given intragastrically to one group at weekly intervals for production of cirrhosis. A control group was maintained under similar conditions except for carbon tetrachloride dosing. The end point for production of cirrhosis was the development of ascites. Two weeks after the development of ascites in the cirrhotic rats and the discontinuation of phenobarbital in both groups, both control and cirrhotic rats were anesthetized with IP pentobarbital and glycine (1.25 g/kg; 7.5%) was given intravenously. Venous blood samples were taken at intervals up to 120 min for serum ammonia analysis. After the final serum ammonia sample, lethal pentobarbital injection was given and livers and kidneys removed for histologic analysis. Terminal body weight, glycine dose, and renal histology were not different between groups. Liver weights were greater in cirrhotic rats. Baseline serum ammonia levels were also greater int he cirrhotic rats.(ABSTRACT TRUNCATED AT 250 WORDS)
Ammonia↗
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.
Adsorption↗