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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-CH2F (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.

Aged↗

Clinical sevoflurane metabolism and disposition. I. Sevoflurane and metabolite pharmacokinetics.

BACKGROUND: Sevoflurane has low blood and tissue solubility and is metabolized to free fluoride and hexafluoroisopropanol (HFIP). Although sevoflurane uptake and distribution and fluoride formation have been described, the pharmacokinetics of HFIP formation and elimination are incompletely understood. This investigation comprehensively characterized the simultaneous disposition of sevoflurane, fluoride, and HFIP. METHODS: Ten patients within 30% of ideal body weight who provided institutional review board-approved informed consent received sevoflurane (2.7% end-tidal, 1.3 MAC) in oxygen for 3 h after propofol induction, after which anesthesia was maintained with propofol, fentanyl, and nitrous oxide. Sevoflurane and unconjugated and total HFIP concentrations in blood were determined during anesthesia and for 8 h thereafter. Plasma and urine fluoride and total HFIP concentrations were measured during and through 96 h after anesthetic administration. Fluoride and HFIP were quantitated using an ion-selective electrode and by gas chromatography, respectively. RESULTS: The total sevoflurane dose, calculated from the pulmonary uptake rate, was 88.8 +/- 9.1 mmol. Sevoflurane was rapidly metabolized to the primary metabolites fluoride and HFIP, which were eliminated in urine. HFIP circulated in blood primarily as a glucuronide conjugate, with unconjugated HFIP < or = 15% of total HFIP concentrations. In blood, peak unconjugated HFIP concentrations were less than 1% of peak sevoflurane concentrations. Apparent renal fluoride and HFIP clearances (mean +/- SE) were 51.8 +/- 4.5 and 52.6 +/- 6.1 ml/min, and apparent elimination half-lives were 21.4 +/- 2.8 and 20.1 +/- 2.6 h, respectively. Renal HFIP and net fluoride excretion were 4,300 +/- 540 and 3,300 +/- 540 mumol. Compared with the estimated sevoflurane uptake, 4.9 +/- 0.5% of the dose taken up was eliminated in the urine as HFIP. For fluoride, 3.7 +/- 0.4% of the sevoflurane dose taken up was eliminated in the urine, which, because a portion of fluoride is sequestered in bone, corresponded to approximately 5.6% of the sevoflurane dose metabolized to fluoride. CONCLUSIONS: Sevoflurane was rapidly metabolized to fluoride and HFIP, which was rapidly glucuronidated and eliminated in the urine. The overall extent of sevoflurane metabolism was approximately 5%.

1-Propanol↗

Analgesia with sevoflurane during labour: ii. Sevoflurane compared with Entonox for labour analgesia.

BACKGROUND: We determined the optimal inspired sevoflurane concentration for use during labour as 0.8% in our previous study. This study compared sevoflurane at a concentration of 0.8% and Entonox((R)) (nitrous oxide 50%: oxygen 50%) for analgesia during labour in 32 healthy parturients. METHODS: Each mother underwent two open-label, three-part sequences in random order, Entonox-sevoflurane-Entonox or sevoflurane-Entonox-sevoflurane. In each part the agent was self-administered during 10 contractions. A 100 mm visual analogue scores for pain relief and sedation was completed immediately after each contraction. RESULTS: Two patients withdrew during administration of sevoflurane (because of its odour) and five during Entonox (requesting epidural analgesia). Of the remaining women, data were available for analysis from 29 participants: median (IQR [range]) pain relief scores were significantly higher for sevoflurane 67 (55-74 [33-100]) mm than for Entonox 51 (40-69.5 [13-100]) mm (P<0.037). Nausea and vomiting were more common in the Entonox group [relative risk 2.7 (95% CI 1.3-5.7); P=0.004]. No other adverse effects were observed in the mothers or babies. There was significantly more sedation with sevoflurane than with Entonox {74 (66.5-81 [32.5-100]) and 51 (41-69.5 [13-100]) mm, respectively; P<0.001}. Twenty-nine patients preferred sevoflurane to Entonox and found its sedative effects helpful. CONCLUSIONS: We conclude that self-administered sevoflurane at subanaesthetic concentration (0.8%) can provide useful pain relief during the first stage of labour, and to a greater extent than Entonox. Although greater sedative effects were experienced with sevoflurane, it was preferred to Entonox.

Adult↗

Comparison of induction, maintenance, and recovery characteristics of sevoflurane-N2O and propofol-sevoflurane-N2O with propofol-isoflurane-N2O anesthesia.

Induction of, maintenance of, and recovery from sevoflurane anesthesia were compared with propofol and isoflurane anesthesia when administered with nitrous oxide to patients undergoing gynecologic surgery. Seventy-five healthy (ASA I or II), consenting patients were randomly assigned to receive either (I) propofol for induction of anesthesia and isoflurane-nitrous oxide for maintenance (control), (II) propofol for induction and sevoflurane-nitrous oxide for maintenance, or (III) sevoflurane-nitrous oxide for induction and maintenance of anesthesia. Inhaled induction of anesthesia with sevoflurane-nitrous oxide was rapid (109 +/- 25 s to loss of consciousness) and without any untoward hemodynamic changes or episodes of coughing and laryngospasm. Mean arterial blood pressure after induction of anesthesia with propofol (71 +/- 11, 73 +/- 12 mm Hg for groups I and II, respectively) was lower than when sevoflurane (80 +/- 14 mm Hg) was used. The emergence time after discontinuation of isoflurane-nitrous oxide (6.7 +/- 2.2 min) was significantly longer than after propofol-sevoflurane-nitrous oxide or sevoflurane-nitrous oxide alone (4.1 +/- 2.2 and 4.0 +/- 2.0 min for groups II and III, respectively). However, later recovery events did not differ between groups. Serum fluoride levels increased after administration of sevoflurane but not isoflurane. The levels of fluoride ions correlated with the degree of exposure to sevoflurane in MAC-hours. In conclusion, induction of anesthesia with either propofol or sevoflurane-nitrous oxide was rapid and without significant side effects. Emergence and early recovery after maintenance of anesthesia with sevoflurane-nitrous oxide was significantly faster than that after an isoflurane-nitrous oxide combination.

Adult↗

Trabecular outflow facility and formation rate of aqueous humor during anesthesia with sevoflurane-nitrous oxide or sevoflurane-remifentanil in rabbits.

UNLABELLED: In the present study, we examined the effect of sevoflurane and remifentanil on intraocular pressure (IOP) and fluid dynamics. Twenty-eight rabbits were anesthetized with halothane, and IOP was measured via a 25-gauge needle in the anterior chamber. Rabbits were then assigned to one of four groups, and halothane was replaced with sevoflurane 1% (n = 7), 2% (n = 7), 3% (n = 7), or 1% + remifentanil 0.65 microg kg(-1) x min(-1) i.v. (n = 7). In all groups, a series of intraocular infusions was made into the anterior chamber, and IOP, trabecular outflow facility, the rate of aqueous humor formation, and intraocular compliance were determined. With sevoflurane only, intraocular compliance decreased (55 +/- 14, 39 +/- 22, 31 +/- 17 nL/mm Hg; P < 0.05) as the concentration of sevoflurane increased. With sevoflurane 1% + remifentanil, intraocular compliance was significantly increased (100.1 +/- 30.5 nL/mm Hg; P < 0.05) compared with sevoflurane 1%, 2%, or 3%. Trabecular outflow facility, rate of aqueous humor formation, and IOP did not differ among groups, and IOP was similar to values obtained during halothane anesthesia. IMPLICATIONS: The dose-related effects of sevoflurane on intraocular compliance did not produce significant intraocular pressure differences. Adding remifentanil to sevoflurane increased intraocular compliance. Sevoflurane or sevoflurane + remifentanil causes a decrease in intraocular pressure compared with the average of previously reported values in awake rabbits, and the magnitude of the decrease is similar to that previously reported in rabbits anesthetized with ethyl urethane, pentobarbital, or halothane alone or in combination with propofol, cocaine, or lidocaine.

Anesthesia↗

A comparison of sevoflurane-propofol versus sevoflurane or propofol for laryngeal mask airway insertion in adults.

In a prospective, randomized study, we investigated the incidence of successful insertion of laryngeal mask airway (LMA) at the first attempt and the incidence of side effects after LMA insertion using the combination of sevoflurane and propofol as compared with either sevoflurane or propofol alone for induction of anesthesia. Eighty-three unpremedicated ASA physical status I-II patients were anesthetized with a single vital capacity breath (VCB) of sevoflurane 8% supplemented with IV propofol 1.5 mg/kg, a single VCB of sevoflurane 8%, or IV propofol 3 mg/kg. The coinduction technique was associated with the most frequent incidence of successful LMA insertion at the first attempt (93.5%) than either sevoflurane alone (46%) or propofol alone (61.5%) (P < 0.001). Propofol-induced induction of anesthesia allowed the fastest insertion of LMA and was associated with the least frequent incidence of postoperative nausea and vomiting. However, this advantage of propofol was offset by a frequent incidence of pain on injection (69%) and the occurrence of movements during insertion of the LMA (50% in the propofol group versus 19% and 26% in the sevoflurane and sevoflurane-propofol groups, respectively; P < 0.05), as well as a more frequent incidence of apnea (84% in the propofol group versus 7% and 16% in the sevoflurane and sevoflurane-propofol groups, respectively; P < 0.001). The report shows that induction of anesthesia with sevoflurane-propofol combined provides a frequent incidence of successful LMA insertion at the first attempt that is associated with an infrequent incidence of apnea.

Adolescent↗

Urinary sevoflurane and hexafluoro-isopropanol as biomarkers of low-level occupational exposure to sevoflurane.

OBJECTIVES: Sevoflurane is an inhalation halogenated anaesthetic widely used in day and paediatric surgery. We were interested in evaluating biological markers of exposure to sevoflurane, which should improve the health surveillance of occupationally exposed personnel. METHODS: A group of 36 subjects (13 male, 23 female) occupationally exposed to volatile anaesthetics in paediatric operating rooms was studied in a 2-week survey. Post-shift urine samples and specimens from passive samplers (for personal monitoring) were collected after 1.75-6 h morning exposure and analysed by headspace gas chromatography-mass spectrometry (GC-MS). Multiple determinations were assumed as independent values (in total, n = 78: 24 from men, 54 from women; 25 from smokers, 53 from non-smokers). RESULTS: Median sevoflurane external values were 0.13 parts per million (ppm) (range 0.03-18.82) (n = 78), urinary sevoflurane 0.6 microg/l urine (ND-18.5)(n = 76) and total urinary hexafluoro-isopropanol (HFIP) 0.49 mg/l urine (ND-6833.4) (n = 75). A lower limit of detection (LOD) was achieved for urinary sevoflurane (0.03 microg/l urine), allowing quantitation of all but one of the samples; >25% of urine samples were unquantifiable by HFIP and were assigned a value equal to half the LOD of 0.10 mg/l(urine). Urinary sevoflurane correlated well with breathing-zone data (r2 = 0.697 at log-log linear regression), whereas total urinary HFIP (r2 = 0.562 at log-log linear regression) seemed to be better described by a three-parameter logistic function and appeared to be influenced by smoking habits. Biological indices corresponding to National Institute for Occupational Safety and Health (NIOSH) exposure limits, calculated as means of linear regression slope and y intercept, were 3.9 mug/l(urine) and 1.4 microg/l urine for sevoflurane (corresponding to 2 ppm and 0.5 ppm, respectively), and 2.66 mg/l urine and 0.82 mg/l urine for HFIP. CONCLUSIONS: On the basis of our data, urinary unmodified, sevoflurane seems to be a more sensitive and reliable biomarker of short-term exposure to sevoflurane with respect to total urinary metabolite HFIP, which appears to be influenced by physiological and/or genetic individual traits, and seems to provide an estimate of integrated exposure.

2-Propanol↗

Cardiovascular homeostasis during inhalational general anesthesia: a clinical comparison between sevoflurane and isoflurane. On behalf of the Italian Research Group on sevoflurane.

STUDY OBJECTIVE: To obtain more information on cardiovascular homeostasis and patient discharge from the recovery area after general anesthesia with either sevoflurane or isoflurane as the main anesthetic. DESIGN: Prospective, randomized, multicenter study. SETTING: Inpatient anesthesia at 13 University Departments of Anesthesia. PATIENTS: 247 ASA physical status I, II, and III patients, aged 18 to 85 years, receiving general anesthesia for elective urological, orthopedic, ENT, vascular, and low abdominal surgery. INTERVENTIONS: General anesthesia was maintained using a 60% nitrous oxide in oxygen mixture with either isoflurane (n = 125) or sevoflurane (n = 122) adjusted according to hemodynamic variables. MEASUREMENTS AND MAIN RESULTS: Occurrence of hypotension [systolic arterial blood pressure (SBP) decrease >30% from baseline], hypertension (SBP increase >30% from baseline), bradycardia [heart rate (HR) <50 bpm], or tachycardia (HR>100 bpm) provoked stepwise changes in the inspired concentration of the study drug. If this action proved to be ineffective after an adequate stabilization period, a specific treatment was given, and the need for pharmacological treatment was recorded as a hemodynamic side effect by an independent observer. No differences in duration of anesthesia were observed between sevoflurane (126 +/- 76 min) and isoflurane patients (139 +/- 60 min). Mean duration from anesthetic discontinuation to fulfillment of discharge criteria was shorter after sevoflurane (21 min; 25(th) to 75(th) percentiles: 27 to 13 min) than isoflurane (27 min; 25(th) to 75(th) percentiles: 17 to 35 min) (p < 0.0005). Hemodynamic side effects requiring therapy occurred in 18 sevoflurane patients (14.6%) and 26 isoflurane patients (20.8%) (p = NS). The risk for hemodynamic side effects increased with age (>50 vs. < or OFFyrs: odds ratio 2.5; 95% CI 1.2 to 5.4; p = 0.015) and ASA physical status (III vs. I and II: odds ratio 2.2; 95% CI 0.9 to 5.7; p = 0.048). When only patients over 50 years of age were considered (72 in the sevoflurane group and 79 in the isoflurane group), the incidence of hemodynamic side effects was higher with isoflurane (29.1%) than with sevoflurane (15.2%) (odds ratio 2.3; 95% CI 1.0 to 5.2; p = 0.04). CONCLUSIONS: Sevoflurane provided equally safe and effective control of cardiovascular homeostasis as isoflurane, with a more rapid discharge from the recovery area. Interestingly, patients over 50 years of age showed a lower risk for hemodynamic side effects when receiving sevoflurane than isoflurane.

Adolescent↗

The hemodynamic and renal effects of sevoflurane and isoflurane in patients with coronary artery disease and chronic hypertension. Sevoflurane Ischemia Study Group.

In patients without significant cardiovascular disease, the hemodynamic effects of sevoflurane and isoflurane are similar; however, the hemodynamic effects of sevoflurane in patients with hypertension and ischemic heart disease are unknown. To examine the effects of sevoflurane in comparison to isoflurane in this high-risk population, 214 patients scheduled for elective surgery were enrolled if they had evidence of ischemic heart disease or multiple risk factors for ischemic heart disease. Patients were randomly assigned to receive sevoflurane (n = 106) or isoflurane (n = 108) for anesthetic maintenance in conjunction with fentanyl and nitrous oxide in oxygen. Deviations in arterial blood pressure or heart rate of more than 20% from preinduction values that persisted after adjustment of the volatile anesthetic concentration were treated with intravenous phenylephrine, ephedrine, nitroglycerin, atropine, or esmolol as needed. Creatinine, blood urea nitrogen (BUN), and urine protein were measured before surgery, immediately after surgery, and 24 and 48 h postoperatively. For analysis, patients were divided into those with and those without the diagnosis of chronic hypertension. Heart rate and arterial blood pressure responses to sevoflurane and isoflurane were not different for the patients with or without chronic hypertension. Neither anesthetic was associated with a more frequent treatment for hemodynamic deviation. After surgery, creatinine and BUN decreased in both the sevoflurane and isoflurane groups without significant differences between groups. The incidence of post-operative proteinuria was similar in the sevoflurane and isoflurane groups. We conclude that hemodynamic stability in patients with hypertension and ischemic heart disease is similar with sevoflurane and isoflurane. No differences in renal function were observed between the sevoflurane and isoflurane groups.

Adult↗

Sevoflurane and bradykinin-induced calcium mobilization in pulmonary arterial valvular endothelial cells in situ: sevoflurane stimulates plasmalemmal calcium influx into endothelial cells.

Kinins locally synthesized in the cardiovascular tissue are believed to contribute to the regulation of cardiovascular homeostasis by stimulating the endothelial cells to release nitric oxide, prostacyclin, or a hyperpolarizing factor via autocrine-paracrine mechanisms. This study was designed to investigate the action of sevoflurane on bradykinin-induced Ca2+ mobilization in endothelial cells in situ. Utilizing fura-2-loaded rat pulmonary arterial valve leaflets, the effects of sevoflurane were examined on bradykinin-induced increases in intracellular Ca2+ concentration ([Ca2+]i) in endothelial cells in situ. In the presence of extracellular Ca2+ (1.5 mM), bradykinin (3-30 microM) produced an initial phasic and a subsequent tonic increase in [Ca2+]i in a concentration-dependent manner. However, it produced only the phasic increase in [Ca2+]i in the absence of extracellular Ca2+. Sevoflurane (5%, 0.67 mM) inhibited both the phasic and tonic responses to bradykinin. In these experiments, sevoflurane (3-5%) generated sustained increases (approximately 20-40% of the bradykinin-induced maximal increase in [Ca2+]i) in the resting [Ca2+]i level. Sevoflurane still increased [Ca2+]i after depletion of the intracellular Ca stores with ionomycin (0.1 microM ). However, the sevoflurane-induced increase in [Ca2+]i was eliminated by removal of the extracellular Ca and attenuated by NiCl (1-3 mM). In conclusion, in the pulmonary arterial valvular endothelial cells, sevoflurane inhibits both bradykinin-induced Ca2+ release from the intracellular stores and bradykinin-induced plasmalemmal Ca2+ influx. In addition, sevoflurane appears to stimulate the plasmalemmal Ca2+ influx and thereby increase the endothelial [Ca2+]i level. Sevoflurane might influence the pulmonary vascular tone through its direct action on the pulmonary arterial valvular endothelial cells.

Anesthetics, Inhalation↗

Infusion of guaifenesin, ketamine, and medetomidine in combination with inhalation of sevoflurane versus inhalation of sevoflurane alone for anesthesia of horses.

OBJECTIVE: To evaluate effects of infusion of guaifenesin, ketamine, and medetomidine in combination with inhalation of sevoflurane versus inhalation of sevoflurane alone for anesthesia of horses. DESIGN: Randomized clinical trial. ANIMALS: 40 horses. PROCEDURE: Horses were premedicated with xylazine and anesthetized with diazepam and ketamine. Anesthesia was maintained by infusion of guaifenesin, ketamine, and medetomidine and inhalation of sevoflurane (20 horses) or by inhalation of sevoflurane (20 horses). A surgical plane of anesthesia was maintained by controlling the inhaled concentration of sevoflurane. Sodium pentothal was administered as necessary to prevent movement in response to surgical stimulation. Hypotension was treated with dobutamine; hypoxemia and hypercarbia were treated with intermittent positive-pressure ventilation. The quality of anesthetic induction, maintenance, and recovery and the quality of the transition to inhalation anesthesia were scored. RESULTS: The delivered concentration of sevoflurane (ie, the vaporizer dial setting) was significantly lower and the quality of transition to inhalation anesthesia and of anesthetic maintenance were significantly better in horses that received the guaifenesin-ketamine-medetomidine infusion than in horses that did not. Five horses, all of which received sevoflurane alone, required administration of pentothal. Recovery time and quality of recovery were not significantly different between groups, but horses that received the guaifenesin-ketamine-medetomidine infusion required fewer attempts to stand. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggest that in horses, the combination of a guaifenesin-ketamine-medetomidine infusion and inhalation of sevoflurane resulted in better transition and maintenance phases while improving cardiovascular function and reducing the number of attempts needed to stand after the completion of anesthesia, compared with inhalation of sevoflurane.

Anesthesia↗

Sevoflurane-maintained anesthesia induced with propofol or sevoflurane in small children: induction and recovery characteristics.

PURPOSE: To compare the induction and recovery characteristics of sevoflurane anesthesia induced with either propofol or sevoflurane in pediatric outpatients. METHODS: Fifty-two children, aged 1-3 yr, presenting for ambulatory adenoidectomy were randomly allocated to receive 3 mg.kg-1 propofol i.v. or sevoflurane 8% inspired concentration for induction of anesthesia. Tracheal intubation was facilitated with 0.2 mg.kg-1 mivacurium. Anesthesia was maintained with nitrous oxide/oxygen (FiO2 0.3) and sevoflurane approximately 3-5% inspired concentration with controlled ventilation. Intubation was assessed by an anesthetist blinded to the induction method. Recovery characteristics were compared using the modified Aldrete scoring system, the Pain/Discomfort scale and measuring specific recovery times. A postoperative questionnaire was used to evaluate the children's well-being at home. RESULTS: Intubating conditions were similar in both groups. Emergence from anesthesia occurred earlier with sevoflurane for induction than with propofol (11 +/- 4 vs 17 +/- 7 min (mean +/- SD), P = 0.0002). More children in the sevoflurane group achieved full points on the modified Aldrete scoring system during the first 20 min after anesthesia (P < 0.05). However, children in the sevoflurane group scored higher in the Pain/Discomfort scale at 10 min after anesthesia (P = 0.04) and were given postoperative analgesics earlier than children in the propofol group (13 +/- 5 min vs 18 +/- 11 min, P = 0.03). The time to meet discharge criteria and recovery at home were similar. CONCLUSIONS: Induction of sevoflurane anesthesia with propofol for day-case adenoidectomy results in longer, but more calm, early recovery but does not delay discharge or affect recovery at home.

Adenoidectomy↗

Uptake and biotransformation of sevoflurane in humans: a comparative study of sevoflurane with halothane, enflurane, and isoflurane.

STUDY OBJECTIVE: To compare the volatile anesthetic sevoflurane with halothane, enflurane, and isoflurane on the uptake and biotransformation in humans. DESIGN: Prospective pharmacokinetic study of sevoflurane administration in human subjects. SETTING: Inpatient surgery clinic at a university medical center. PATIENTS: Thirty-two Japanese patients, free of systemic diseases, undergoing minor elective surgery with endotracheal general anesthesia. INTERVENTIONS: The patients were assigned randomly to one of four groups: halothane, enflurane, isoflurane, or sevoflurane. One of the four volatile anesthetics being investigated [equivalent to 1.1 minimum alveolar concentration (MAC): halothane, 0.85%; enflurane, 1.85%; isoflurane, 1.27%; and sevoflurane, 1.88%; in inspired concentrations throughout the first hour of anesthesia] was administered for 60 minutes. MEASUREMENTS AND MAIN RESULTS: In all patients, serum and urinary fluoride concentrations were measured. The concentrations of all gases were measured separately with a mass spectrometer. The cumulative uptake of each anesthetic agent during a certain period was calculated as an integration of the uptake rate per minute. The results for one-hour inhalation of sevoflurane (1.1 MAC) showed an uptake (corrected for body surface area and MAC) of 490 ml/m2/MAC and estimated degradation rate of 3.3%. For purposes of comparison, similar studies of halothane (uptake, 653 ml/m2/MAC; degradation rate 15.7%), enflurane (1150 ml/m2/MAC; 1.3%), and isoflurane (439 ml/m2/MAC; 0.6%) were also conducted. Sevoflurane had a peak serum inorganic fluoride concentration of 19.3 mumol/L, and no abnormality in hepatic or renal functions was observed in any of the subjects during the two weeks postoperatively. CONCLUSIONS: Accurate determinations of uptake and degradation rate for sevoflurane and three other volatile anesthetics in Japanese patients were obtained. These findings have established that, despite its relatively large MAC (1.71%), sevoflurane has a small uptake due to its low solubility. However, the degradation rate was shown to be as high as 3.3%, resulting in a higher serum fluoride concentration than seen after administration of isoflurane, halothane, and (possibly) enflurane.

Adult↗

A multicenter comparison of maintenance and recovery with sevoflurane or isoflurane for adult ambulatory anesthesia. The Sevoflurane Multicenter Ambulatory Group.

Sevoflurane was compared with isoflurane in 246 adult ASA class I-III patients undergoing ambulatory surgery. After administration of midazolam 1-2 mg and fentanyl 1 microgram/kg, anesthesia was induced with propofol 2 mg/kg and maintained with either sevoflurane or isoflurane in 60% nitrous oxide to maintain arterial blood pressure at +/- 20% of baseline. Fresh gas flows were 10 L/min during induction and 5 L/min during maintenance. Times to eye opening, command response, orientation, and ability to sit without nausea and/or dizziness were significantly faster after sevoflurane. Significantly more sevoflurane patients met Phase 1 of postanesthesia care unit (PACU) Aldrete recovery criteria (> or = 8) at arrival, 95% vs 81%. Also, significantly more sevoflurane patients were able to complete psychomotor recovery tests during the first 60 min postanesthesia. Discharge times were not different. Sevoflurane patients had significantly lower incidences of postoperative somnolence (15% vs 26%) and of nausea both in the PACU (36% vs 51%) and in the 24-h postdischarge period (9% vs 24%). Patient satisfaction was high overall (sevoflurane 97%, isoflurane 93%). We conclude that sevoflurane is a useful inhaled anesthetic for maintenance of ambulatory anesthesia.

Adult↗

A comparison of the effects of prolonged (>10 hour) low-flow sevoflurane, high-flow sevoflurane, and low-flow isoflurane anaesthesia on hepatorenal function in orthopaedic patients.

This study compared the effects of low-flow sevoflurane, high-flow sevoflurane and low-flow isoflurane on hepatorenal function during and after more than 10 hours of anaesthesia. Twenty-five patients scheduled for elective orthopaedic surgery were categorized into three groups; low-flow sevoflurane (fresh gas flow at 1 litre/min, n = 9), high-flow sevoflurane (5 l/rmin, n = 7), or low-flow isoflurane (1 l/min, n=9). Inspiratory compoundA concentrations were measured. The groups had similar duration of anaesthesia and exposure to anaesthetic agents. The area under the curve of concentration (mean, SD) of compound A in the low-flow sevoflurane group (359.8, 106.1 ppm.h) was greater than that in the high-flow sevoflurane group (61.1, 29.3 ppm.h; P<0.01). All groups showed normal plasma creatinine and creatinine clearance, and transient postoperative increases in plasma alanine aminotransferase and alpha glutathione-S-transferase, as well as urinary glucose and alpha glutathione-S-transferase, with no significant differences between groups. There were no significant relationships between the area under the curve of concentration of compound A and the biomarkers. These findings suggest that prolonged anaesthesia with low-flow sevoflurane has similar effects on hepatorenal function to prolonged anaesthesia with high-flow sevoflurane and low-flow isoflurane.

Adult↗

Does halothane really preserve cardiac baroreflex better than sevoflurane? A noninvasive study of spontaneous baroreflex in children anesthetized with sevoflurane versus halothane.

Heart rate profiles during the induction of anesthesia differ markedly between the administration of sevoflurane and halothane. Previous investigations have shown that halothane preserves cardiac parasympathetic activity more than sevoflurane. Because vagal drive to the sinus node is the main effector of arterial baroreflex control of heart rate, halothane may preserve cardiac baroreflex better than sevoflurane. To investigate cardiac baroreflex in anesthetized children, we used two noninvasive methods providing different approaches to the arterial blood pressure (BP) and R-R interval (RRI) relationship: the sequence methods investigating beat-to-beat changes in BP and RRI (time domain) and the cross-spectral analysis investigating relationships between oscillations of BP and RRI (frequency domain). Children were randomly assigned to mask induction with sevoflurane in 100% oxygen, sevoflurane in 50% nitrous oxide/50% oxygen, or halothane in 50% nitrous oxide/50% oxygen. After tracheal intubation, the inspired fraction of volatile anesthetic was reduced to 1 minimum alveolar anesthetic concentration (MAC). The spontaneous baroreflex (SBR) sensitivity was calculated with the sequence method at baseline, during induction, and after intubation. The cardiac baroreflex was also estimated with cross-spectral analysis at baseline and at 1 MAC (stationary conditions). In the three groups, the induction of anesthesia was associated with a marked decrease of SBR sensitivity, which occurred earlier with sevoflurane than with halothane. Five minutes after intubation (1 MAC), the sequence method showed a similar decrease of the SBR sensitivity in the three groups. Similarly, the cross-spectral analysis between systolic blood pressure and RRI showed a decrease of the gain calculated in the low-frequency band, but the gain in the respiratory band was higher with halothane compared with sevoflurane. In children, the induction of anesthesia with halothane and sevoflurane is associated with a marked decrease of cardiac baroreflex activity. The persistence of respiratory RRI fluctuations under halothane might reflect reflex respiratory arrhythmia rather than efficient parasympathetic baroreflex activity.

Anesthetics, Inhalation↗

[Comparative study of inhalation induction by vital capacity breath in adults using 6% sevoflurane with oxygen or 4.5%sevoflurane in 50% nitrous oxide].

OBJECTIVE: To evaluate the efficacy, side effects and hemodynamic characteristics of induction by vital capacity breath in adults using 6% sevoflurane and oxygen versus 4.5% sevoflurane and 50% nitrous oxide. PATIENTS AND METHODS: We assigned 50 ASA I-II patients aged 20 to 70 years old randomly to two groups of 25 to receive either 6% sevoflurane in oxygen or 4.5% sevoflurane in nitrous oxide. All patients were premedicated with oral bromazepam (1.5 to 3 mg). Induction was by vital capacity breath using a Mapleson A circuit (8 l. min-1) for 5 min. We recorded induction time, side effects, hemodynamic variables and patient opinion after surgery. RESULTS: Induction time was significantly faster for the sevoflurane-oxygen group (60 +/- 10 s) than for the sevoflurane-nitrous oxide group (71 +/- 8 s) (p < 0.001). Complications were minor and hemodynamic variables stable in both groups, with no statistically significant differences. The patients expressed satisfaction with both induction techniques. CONCLUSIONS: A vital capacity breath of 6% sevoflurane provided rapid induction. Induction was no more rapid when 50% nitrous oxide was added and the incidence of side effects did not decrease. Hemodynamic variables are stable during induction with sevoflurane with or without nitrous oxide, making this a well-tolerated alternative technique that is positively evaluated by patients.

Adult↗

The distribution of sevoflurane in a sevoflurane induced death.

The distribution of sevoflurane (fluoromethyl 2,2,2,-trifluoro-1-(trifluoromethyl) ethyl ether) in blood, urine, liver, kidney, vitreous humor, and tracheal aspirate is presented from a subject with a sevoflurane induced death. Sevoflurane is a nonflammable general anesthetic administered by inhalation of vaporized liquid. Although general inhalation anesthetics have the potential to be fatal if not properly administered, the incidence of abuse is minute in comparison to other illicit drugs. Currently, there are no citations in the literature defining the body distribution of sevoflurane in a sevoflurane induced death. The decedent was found lying in a bed with an oxygen mask containing a gauze pad secured to his face. Three empty bottles and one partially full bottle of Ultane (sevoflurane) were found with the body in addition to two pill boxes containing a variety of prescription and non-prescription drugs. Serum, urine and gastric contents from the deceased were screened for numerous drugs and metabolites using a combination of thin layer chromatographic, colorimetric and immunoassay techniques. Analysis of biological specimens from the deceased revealed the presence of: amphetamine, caffeine, pseudoephedrine, nicotine, nicotine metabolite, and valproic acid. Sevoflurane concentrations were determined by headspace gas chromatography with flame ionization detection and revealed concentrations of 26.2 microg/mL in the blood, 105 microg/mL in the urine, 31.9 microg/mL in the tracheal aspirate, 86.7 microg/mL in the vitreous humor, 30.8 mg/kg in the liver, and 12.8 mg/kg in the kidney. The decedent had pathologies consistent with respiratory suppression including pulmonary atelectasis, pulmonary edema, and neck vein distention. The official cause of death was respiratory suppression by sevoflurane and the manner of death was unclear.

Adult↗