Hiromichi Bito

The Effect of Fentanyl on Sevoflurane Requirements for Somatic and Sympathetic Responses to Surgical Incision

BACKGROUND Fentanyl produces a reduction in the minimum alveolar concentration (MAC) of isoflurane and desflurane needed to blockade adrenergic response (BAR) to surgical incision in 50% of patients (MAC-BAR). MAC-BAR of sevoflurane and the reduction in MAC-BAR of sevoflurane by fentanyl have not been described previously. The purpose of this study was to determine the MAC and MAC-BAR reduction of sevoflurane by fentanyl with and without nitrous oxide (N2O). METHODS Two hundred twenty-six patients were randomly assigned to one of two groups: a sevoflurane group and a sevoflurane/N2O group. Patients in each group were randomly assigned to one of five different fentanyl concentration subgroups. Patients were anesthetized with sevoflurane and fentanyl in the sevoflurane group and with sevoflurane, fentanyl, and N2O (66 vol%) in the sevoflurane/N2O group. Somatic and sympathetic responses to surgical incision were observed for MAC and MAC-BAR assessment at predetermined concentrations of sevoflurane. RESULTS Fentanyl produced an initial steep reduction in the MAC and MAC-BAR of sevoflurane, with 3 ng/ml resulting in a 61% reduction in MAC and an 83% reduction in MAC-BAR. A ceiling effect was observed for MAC and MAC-BAR, with 6 ng/ml fentanyl providing only an additional 13% and 9% reduction in MAC and MAC-BAR, respectively. In the presence of 66 vol% N2O, MAC and MAC-BAR of sevoflurane were reduced with increasing concentrations of fentanyL A ceiling effect was not observed for reduction in MAC and MAC-BAR in the presence of N2O. CONCLUSIONS MAC and MAC-BAR decreased similarly with increasing concentrations of fentanyl in plasma, showing an initial steep reduction followed by a ceiling effect. In the presence of N2O, MAC and MAC-BAR decreased similarly but did not exhibit a ceiling effect.

Effects of Low-flow Sevoflurane Anesthesia on Renal Function Comparison with High-flow Sevoflurane Anesthesia and Low-flow Isoflurane Anesthesia

Background: The safety of low-flow sevoflurane anesthesia, during which CF2 = C(CF3)-O-CH2 F (compound A) is formed by sevoflurane degradation, in humans has been questioned because compound A is nephrotoxic in rats. Several reports have evaluated renal function after closed-circuit or low-flow sevoflurane anesthesia, using blood urea nitrogen (BUN) and serum creatinine as markers. However, these are not the more sensitive tests for detecting renal damage. This study assessed the effects of low-flow sevoflurane anesthesia on renal function using not only BUN and serum creatinine but also creatinine clearance and urinary excretion of kidney-specific enzymes, and it compared these values with those obtained in high-flow sevoflurane anesthesia and low-flow isoflurane anesthesia. Methods: Forty-eight patients with gastric cancer undergoing gastrectomy were studied. Patients were randomized to receive sevoflurane anesthesia with fresh gas flow of 1 l/min (low-flow sevoflurane group; n = 16) or 6–10 l/min (high-flow sevoflurane group; n = 16) or isoflurane anesthesia with a fresh gas flow of 1 l/min (low-flow isoflurane group; n = 16). In all groups, the carrier gas was oxygen/nitrous oxide in the ratio adjusted to ensure a fractional concentration of oxygen in inspired gas (FiO2) of more than 0.3. Fresh Baralyme was used in the low-flow sevoflurane and low-flow isoflurane groups. Glass balls were used instead in the high-flow sevoflurane group, with the fresh gas flow rate adjusted to eliminate rebreathing. The compound A concentration was measured by gas chromatography. Gas samples taken from the inspiratory limb of the circle system at 1-h intervals were analyzed. Blood samples were obtained before and on days 1, 2, and 3 after anesthesia to measure BUN and serum creatinine. Twenty-four-hour urine samples were collected before anesthesia and for each 24-h period from 0 to 72 h after anesthesia to measure creatinine, N-acetyl-beta-D-glucosaminidase, and alanine aminopeptidase. Results: The average inspired concentration of compound A was 20 +/- 7.8 ppm (mean +/- SD), and the average duration of exposure to this concentration was 6.11 +/- 1.77 h in the low-flow sevoflurane group. Postanesthesia BUN and serum creatinine concentrations decreased, creatinine clearance increased, and urinary N-acetyl-beta-D-glucosaminidase and alanine aminopeptidase excretion increased in all groups compared with preanesthesia values, but there were no significant differences between the low-flow sevoflurane, high-flow sevoflurane, and low-flow isoflurane groups for any renal function parameter at any time after anesthesia. Conclusions: The only difference between the low-flow and high-flow sevoflurane groups was compound A formation, and postanesthesia laboratory data showed no significant effects of compound A formation during sevoflurane anesthesia on renal function. No significant effects on renal function were observed in either the low-flow or high-flow sevoflurane groups compared with the low-flow isoflurane group.

Influence of Age on Hypnotic Requirement, Bispectral Index, and 95% Spectral Edge Frequency Associated with Sedation Induced by Sevoflurane

Background Aging is associated with a reduction in anesthetic requirements. The effects of age on the electroencephalographic response to inhalational anesthesia have not been well documented. The objective of the present study was to determine the influence of age on hypnotic requirement and electroencephalographic derivatives such as bispectral index and 95% spectral edge frequency associated with sedation induced by sevoflurane. Methods Ninety-six patients were randomly allocated into one of three age groups A, B, and C, ranging in age from 18–39 yr, 40–64 yr, and 65–85 yr, respectively. Patients in each group were sedated with sevoflurane at two predetermined concentrations ranging between 0.45% and 0.85%. The relationship between sevoflurane concentration and response to a verbal command, as well as the relationships between response and bispectral index and 95% spectral edge frequency, was determined. Results Multiple regression analysis showed that end-tidal sevoflurane concentration and age significantly affected both bispectral index and 95% spectral edge frequency. ED50 values of sevoflurane concentration for loss of consciousness, defined as no response to verbal command, were different between groups A and C: 0.72 (95% confidence interval: 0.68–0.75) versus 0.59 (95% confidence interval: 0.56–0.62). However, the same effective values of bispectral index and 95% spectral edge frequency at this same clinical end point did not differ. Conclusions Increasing age reduced sevoflurane requirements to suppress responses to a verbal command but did not change bispectral index and 95% spectral edge frequency associated with this end point, and in a population with a wide age range, bispectral index would predict depth of sedation better than end-tidal sevoflurane concentration.

Closed-circuit anesthesia with sevoflurane in humans. Effects on renal and hepatic function and concentrations of breakdown products with soda lime in the circuit.

BackgroundSevoflurane reacts with CO2 absorbents, resulting in the generation of breakdown products. The concentrations of sevoflurane breakdown products in a low-flow system within 5 h have been reported, but concentrations in low-flow anesthesia exceeding 5 h or in closed-circuit anesthesia have not. In this study, the breakdown products of sevoflurane in closed-circuit anesthesia exceeding 5 h were examined. MethodsClosed-circuit sevoflurane anesthesia was administered to ten patients. Laboratory tests of hepatic and renal function were performed before and after anesthesia. Gas samples were obtained from the inspiratory limb of the anesthesia circuit, and breakdown products were analyzed by gas chromatography. The temperature of the soda lime was measured during anesthesia. ResultsAmong the breakdown products of sevoflurane, two products, CF2 = C(CF3)-O-CH2F (compound A) and CH3OCF2CH(CF3)OCH2F (compound B), were detected. Compound A was detected in all measurements, and its concentration reached 19.5 ± 5.4 ppm 1 h after anesthesia and decreased after 5 h. The highest concentration observed for compound A was 30.0 ppm. Compound B was detected in seven of the ten patients; its concentration was 0.17 ± 0.37 ppm after 0.5 h of anesthesia and remained at similar concentrations thereafter. The highest mean temperature of the soda lime was 46.0 ± 1.7° C. Postanesthetic clinical laboratory tests showed no abnormalities in hepatic or renal function associated with anesthesia. ConclusionsTwo breakdown products were detected in the patients anesthetized with sevoflurane using a closed-circuit technique. No abnormalities were observed during anesthesia, and no evidence of hepatic or renal dysfunction was noted in postoperative laboratory tests.

Long-duration, low-flow sevoflurane anesthesia using two carbon dioxide absorbents. Quantification of degradation products in the circuit.

BackgroundSevoflurane reacts with soda lime, generating degradation products. The concentrations of sevoflurane degradation products in a low-flow circuit have been reported for anesthesia times of less than 5 h. In this study, sevoflurane degradation products generated during low-flow anesthesia exceeding 10 h were examined. MethodsSixteen patients received sevoflurane anesthesia with a fresh gas flow rate of 11/min. In eight patients, soda lime was used as the CO2 absorbent; in the other eight patients, Baralyme was used. During anesthesia, the concentrations of degradation products in the circuit, the temperature of the CO2 absorbent, inspired and end-tidal sevoflurane concentrations, and the volume of CO2 eliminated by the patient were measured. Gas was sampled from the inspiratory limb of the circuit and analyzed by gas chromatography. ResultsTwo degradation products, CF2=C(CF3)—O—CH2F (compound A) and CH3OCF2CH(CF3)OCH2F (compound B), were detected. In the soda lime group, the individual maximum concentration of compound A was 23.6 ± 2.9 (12.0–37.4) ppm. In the Baralyme group, the concentration was 32.0 ± 2.3 (23.5–41.3) ppm. The individual maximum concentration of compound A in the Baralyme group was significant higher than that in the soda lime group. Compound B was detected in two patients, reaching a maximum concentration of 0.2 ppm. The end-tidal sevoflurane concentration, temperature of the CO2 absorbent, and volume of CO2 eliminated by the patient were the same in both groups. ConclusionsThe degradation products detected were at low concentrations in long-duration, low-flow anesthesia with sevoflurane. Baralyme produced higher concentrations of degradation products than soda lime.

Renal and hepatic function in surgical patients after low-flow sevoflurane or isoflurane anesthesia

The safety of low-flow sevoflurane anesthesia, which produces higher concentrations of toxic compounds, has been questioned. One hundred surgical patients received sevoflurane or isoflurane anesthesia at a total flow rate of 1 L/min. End-tidal CO2 concentrations and inspired and end-tidal anesthetic concentrations were monitored during anesthesia. Pre- and postanesthetic clinical laboratory studies were performed in both groups, and no significant differences were found between groups. In the sevoflurane group, the concentrations of degradation products in the circuit were measured by gas chromatography and the temperature of the CO2 absorbent was also measured. Two degradation products were detected: CF2 = C(CF3-O-CH2 F (Compound A) and CH3 OCF2 CH(CF3)OCH2 F (Compound B). The highest measured mean concentration of Compound A was 24.6 +/- 7.2 (13.6-41.3) ppm, and that of Compound B (detected in 12 patients) was 1.5 ppm. In both groups, total bilirubin, direct bilirubin, aspartate aminotransferase, and alanine aminotransferase were increased postoperatively. There was no difference between groups. Low concentrations of Compound A were present in low-flow sevoflurane anesthesia, but no significant differences in clinical laboratory values were observed between low-flow sevoflurane and isoflurane anesthesia. (Anesth Analg 1996;82:173-6)

The effects of prolonged low-flow sevoflurane anesthesia on renal and hepatic function.

UNLABELLED We assessed the effects of prolonged low-flow sevoflurane anesthesia on renal and hepatic functions by comparing high-flow sevoflurane with low-flow isoflurane anesthesia. Thirty patients scheduled for surgery of > or =10 h in duration randomly received either low-flow (1 L/min) sevoflurane anesthesia (n = 10), high-flow (6-10 L/min) sevoflurane anesthesia (n = 10), or low-flow (1 L/min) isoflurane anesthesia (n = 10). We measured the circuit concentrations of Compound A and serum fluoride. Renal function was assessed by blood urea nitrogen, serum creatinine, creatinine clearance, and urinary excretion of glucose, albumin, protein, and N:-acetyl-beta-D-glucosaminidase. The hepatic function was assessed by serum aspartate aminotransferase, alanine aminotransferase, lactate dehydrogenase, alkaline phosphatase, and total bilirubin. Compound A exposure was 277 +/- 120 (135-478) ppm-h (mean +/- SD [range]) in the low-flow sevoflurane anesthesia. The maximum concentration of serum fluoride was 53.6 +/- 5.3 (43.4-59.3) micromol/L for the low-flow sevoflurane anesthesia, 47.1 +/- 21.2 (21.4-82.3) micromol/L for the high-flow sevoflurane anesthesia, and 7.4 +/- 3.2 (3.2-14.0) micromol/L for the low-flow isoflurane anesthesia. Blood urea nitrogen and serum creatinine were within the normal range, and creatinine clearance did not decrease throughout the study period in any group. Urinary excretion of glucose, albumin, protein, and N:-acetyl-beta-D-glucosaminidase increased after anesthesia in all groups, but no significant differences were seen among the three groups at any time point after anesthesia. Lactate dehydrogenase and alkaline phosphatase on postanesthesia Day 1 were higher in the high-flow sevoflurane group than in the low-flow sevoflurane group. However, there were no significant differences in any other hepatic function tests among the groups. We conclude that prolonged low-flow sevoflurane anesthesia has the same effect on renal and hepatic functions as high-flow sevoflurane and low-flow isoflurane anesthesia. IMPLICATIONS During low-flow sevoflurane anesthesia, intake of Compound A reached 277 +/- 120 ppm-h, but the effect on the kidney and the liver was the same in high-flow sevoflurane and low-flow isoflurane anesthesia.

Plasma inorganic fluoride and intracircuit degradation product concentrations in long-duration, low-flow sevoflurane anesthesia

Plasma inorganic fluoride (F−) concentrations in long-duration, low-flow sevoflurane anesthesia were studied to assess effects on renal and hepatic function. The intracircuit concentration of degradation product generated by reaction between sevoflurane and CO2 absorbant was also determined. Ten patients undergoing prolonged surgery of 10 h or longer received sevoflurane anesthesia at 1 L/min. Plasma F− concentration was measured and clinical laboratory tests were performed. Intracircuit gas was analyzed to measure the concentration of degradation products. Plasma F− concentration increased during anesthesia, and decreased 3 h after termination. Individual maximum plasma F− concentrations were 38.8–88.6μmol/L (56.6±4.7μmol/L, mean±se). Minimum alveolar anesthetic concentration (MAC) hours (1 MAC = 2.05%) exposure correlated with individual maximum plasma F− concentration (r2 = 0.68, P < 0.01). CF2 = C(CF3)-O-CH2F (compound A) was the only degradation product detected in the circuit. Its individual maximum concentrations were 13.6–35.1 ppm (24.3±2.4 ppm). Postanesthesia clinical laboratory tests showed no renal impairment and only mild hepatic dysfunction that was not associated with anesthesia. Hyperfluorinemia and minute quantities of compound A were detected following long-duration, low-flow sevoflurane anesthesia.

S-Nitroso-N-acetylpenicillamine (SNAP) during hemorrhagic shock improves mortality as a result of recovery from vascular hyporeactivity

Nitric oxide donors are protective against hemorrhagic shock (HS). However, no detailed investigation has been performed. We investigated this mechanism using S-nitroso-N-acetylpenicillamine (SNAP). HS (mean arterial pressure: 40 mm Hg) was induced in 20 dogs. Sixty min after HS, the animals were treated with saline (Cont-Gr:n = 7) or SNAP; 5 &mgr;g · kg−1 · 10 min−1 fol- lowed by 5 &mgr;g · kg−1 · h−1 (SNAP-Gr:n = 7). After another 60 min, the shed blood was reinfused. Reactivities to noradrenalin (NA), changes in hemodynamics, the plasma catecholamines, and nitric oxide derivatives were determined. In Cont-Gr, 3 dogs died at 90, 98, and 102 min after HS. In Cont-Gr, % changes of systolic arterial blood pressure to 1 and 2.5 &mgr;g/kg of NA after the recovery from HS decreased from 23.7% ± 4.1% (before HS) to 6.5% ± 0.6% and from 50.1% ± 7.7% (before HS) to 14.5% ± 2.6%, respectively (P < 0.01). In SNAP-Gr, reactivity to NA was maintained. At 120 min after HS, mean arterial pressure and cardiac output in SNAP-Gr increased but not in Cont-Gr. Plasma catecholamine levels in SNAP-Gr were suppressed compared with those of Cont-Gr. In conclusion, a small dose of SNAP during HS decreased the mortality of the dogs. This might have been caused in part by residual vascular hyporeactivity. Implications The administration of a small dose of S-nitroso-N-acetylpenicillamine (a nitric oxide donor), a dose which did not exert a significant vasodilator effect, was administered during hemorrhagic shock in dogs. S-nitroso-N-acetylpenicillamine improved the vascular hyporeactivity to noradrenaline and decreased the mortality rate.

effects of the Water Content of Soda Lime on Compound A Concentration in the Anesthesia Circuit in Sevoflurane Anesthesia

Background Sevoflurane anesthesia is usually performed with fresh gas flow rates greater than 2 l/min due to the toxicity of compound A in rats and limited clinical experience with sevoflurane in low‐flow systems. However, to reduce costs, it would be useful to identify ways to reduce compound A concentrations in low‐flow sevoflurane anesthesia. This goal of this study was to determine if compound A concentrations can be reduced by using soda lime with water added. Methods Low‐flow sevoflurane anesthesia (fresh gas flow of 1 l/min) was performed in 37 patients using soda lime with water added (perhydrated soda lime) or standard soda lime as the carbon dioxide (CO sub 2) absorbent. The soda lime was not changed between patients, but rather was used until CO2 rebreathing occurred. The perhydrated soda lime was prepared by spraying 100 ml distilled water onto 1 kg fresh soda lime, and water was added only when a new bag of soda lime was placed into the canister. Compound A concentrations in the circle system, soda lime temperatures, inspired and end‐tidal CO2 and end‐tidal sevoflurane concentrations, and CO2 elimination by the patient were measured during anesthesia. Results Compound A concentrations were significantly lower for the perhydrated soda lime (1.9 +/‐ 1.8 ppm; means +/‐ SD) than for the standard soda lime (13.9 +/‐ 8.2 ppm). No differences were seen between the two types of soda lime with regard to the temperature of the soda lime, end‐tidal sevoflurane concentrations, or CO2 elimination. Compound A concentration decreased with the total time of soda lime use for both types of soda lime. The CO2 absorption capacity was significantly less for perhydrated soda lime than for standard soda lime. Conclusions Compound A concentrations in the circuit can be reduced by using soda lime with water added. The CO2 absorption capacity of the soda lime is reduced by adding water to it, but this should not be clinically significant.