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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↗

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↗

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-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↗

[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↗

Immediate 8% sevoflurane induction in children: a comparison with incremental sevoflurane and incremental halothane.

We compared the efficacy and tolerance of pediatric inductions with immediate 8% sevoflurane in 70% nitrous oxide with either incremental sevoflurane or incremental halothane in 70% nitrous oxide. Forty-six unpremedicated children had anesthesia induced by immediate 8% sevoflurane (high sevoflurane [HS]; circuit primed with 70% N2O and 8% sevoflurane before application of the face mask), gradual sevoflurane (GS; primed with 70% N2O with increments of sevoflurane), and gradual halothane (HAL; 70% N2O with incremental halothane). Blind video recordings were made, and each child's distress was rated prior to mask application, during mask application, and every 10 s thereafter using a behavioral rating scale. There were no complications. Of those subjects not quiet and cooperative throughout, times to complete quiet were significantly different (P = 0.001): HS 19.8 +/- 8 s (range 9-34); GS 52 +/- 17 s (range 8-73); HAL 43 +/- 22 s (range 13-73). Times to eye closure were also significantly different (P < 0.001): HS 37 +/- 10 s (range 15-56); GS 70 +/- 18 s (range 35-114); HAL 81 +/- 34 s (range 55-140). Distress scale scores showed more rapid decrement with HS than with GS or HAL. We conclude that 1) immediate 8% sevoflurane/N2O results in a significantly faster induction than GS or HAL;2) in children, HS in N2O will not result in a single-breath induction under the conditions of this study; 3) in this small group, HS was extremely well tolerated in ASA class I and II patients.

Anesthesia, Closed-Circuit↗

Myocardial ischemia and adverse cardiac outcomes in cardiac patients undergoing noncardiac surgery with sevoflurane and isoflurane. Sevoflurane Ischemia Study Group.

UNLABELLED: Sevoflurane is associated with less tachycardia and coronary vasodilation than isoflurane and thus might be associated with less myocardial ischemia. This multicenter study examined the incidence of myocardial ischemia and adverse cardiac outcomes in adults (40-87 yr) with cardiac disease having elective noncardiac surgery. Patients were randomized to receive either sevoflurane (S) (n = 106) or isoflurane (I) (n = 108) in conjunction with sodium thiopental, vecuronium, fentanyl, and 50%-70% N2O. Intraoperative hemodynamics were maintained within 20% of awake baseline with standard drugs. A Holter monitor was applied 3-24 h before surgery and maintained until 48 h after surgery. Electrocardiograms and blood samples for analysis of the MB isoenzyme fraction of creatine phosphokinase were obtained preoperatively and daily for 48 h postoperatively. Anesthetic exposure (1.79 +/- 0.15 [mean +/- SE] minimum alveolar concentration-hour) and duration of surgery (219 +/- 13 min) did not differ between groups. The incidence of ischemia in the pre-, intra- and postoperative periods, adverse cardiac outcomes (18% occurrence), intraoperative hemodynamic variations (+/-20% change from ward baseline), and administration of adjunct cardiovascular medications were similar between groups. In cardiac patients having noncardiac surgery, sevoflurane was comparable to isoflurane with respect to the incidence of intra- and postoperative myocardial ischemia and in the frequency of adverse cardiac outcomes. IMPLICATIONS: Surgical patients with heart disease are at risk of heart complications, some of which could be induced by an anesthetic. We compared the incidence of cardiac complications between patients receiving sevoflurane and isoflurane. We found that the frequency of additional heart problems in cardiac patients receiving sevoflurane was not different from that associated with isoflurane.

Adult↗

[Effects of inorganic fluoride, inhalation time and dosage of sevoflurane on renal function during sevoflurane anesthesia of long duration].

In sevoflurane anesthesia of long duration, we studied correlations with renal function of the area under the curve (AUC), rate of decrease and maximum level of serum inorganic fluoride (F), sevoflurane dosage, and duration of administration. In 15 neurosurgical patients, we measured serum and urine levels of F, blood urea nitrogen (BUN), creatinine, serum and urine beta 2-microglobulin (BMG), and urine N-acetyl-beta-D-glucosaminidase (NAG). AUC and the rate of decrease of serum F were calculated. There were no correlations among the maximum level, AUC, the rate of decrease of serum F, sevoflurane dosage, duration of administration, BUN, creatinine, BMG, and NAG. It is concluded that in sevoflurane anesthesia of long duration, F, sevoflurane dosage and duration of administration do not affect renal function.

Adult↗

[Changes in circulation and end-tidal sevoflurane concentration during infusion of sevoflurane into vaporizer].

We observed the changes in circulation and endtidal sevoflurane concentration during the infusion of the anesthetic into a vaporizer, and investigated some techniques to prevent these changes during general anesthesia. The patients were randomly divided into three groups: conventional, high concentration (conc.) and low flow groups. Inspiratory concentration of sevoflurane was kept at 1.0% and the duration of the pause in sevoflurane supply was 90 sec. The high conc. group was exposed to 2.0% sevoflurane for 60 sec. just before and after the pause, and the low flow group had a low fresh gas flow (0.5 l.min-1) during the pause. An increase in blood pressure and a tendency towards tachycardia were observed in the conventional group, and the circulation was kept constant best in the low flow group. The lowest concentrations of sevoflurane during the pause were 0.46, 0.46 and 0.93% in the conventional, high conc., and low flow groups, respectively, and exposure to high concentration of the anesthetic could not prevent the decrease. These results indicate that low flow anesthesia is a useful technique to prevent undesirable changes in circulation and anesthetic concentration.

Anesthesia, Epidural↗

Sevoflurane. A review of its pharmacodynamic and pharmacokinetic properties and its clinical use in general anaesthesia.

Sevoflurane is an ether inhalation general anaesthetic agent with lower solubility in blood than isoflurane or halothane but not desflurane. The low solubility and the absence of pungency facilitate rapid mask induction; the low blood solubility also expedites "wash-out' and therefore recovery from anaesthesia. Sevoflurane produces dose-dependent CNS, cardiovascular and respiratory depressant effects that generally parallel those of isoflurane. Sevoflurane is degraded by carbon dioxide absorbents to nephrontoxic (in rats) haloalkenes, although renal toxicity has not been observed in humans. Compared with other inhalation anaesthetics, negligible quantities of carbon monoxide are generated from degradation of sevoflurane by carbon dioxide absorbents. Sevoflurane has negligible airway irritant effects, which facilitates a "smooth' induction, even in comparison with halothane in paediatric patients, and makes sevoflurane especially amenable to rapid induction of anaesthesia in adults and children. Emergence, orientation an postoperative cognitive and psychomotor function recovery of paediatric outpatients is singnificantly more rapid from sevoflurane than from halothane anaesthesia. In adult inpatients and outpatients, emergence and orientation are significantly faster after sevoflurane than after isoflurane but not desflurane anaesthesia. Other recovery parameters (e.g. times to sitting, ambulation) occur at similar times after either sevoflurane or desflurane anaesthesia. Recovery of psychomotor function occurs at generally similar times after sevoflurane, isoflurane or desflurane. Compared with propofol, sevoflurane facilitates more predictable extubation times and significantly better postoperative modified Aldrete scores in outpatients, although cognitive and psychomotor recovery occurs at similar times for both agents. As a supplement to opioid anaesthesia during coronary bypass graft surgery or in those at risk for myocardial ischaemia, sevoflurane is comparable to isoflurane. Limited data suggest that it is also as useful as isoflurane for the maintenance of anaesthesia during neurosurgical or obstetric procedures. Sevoflurane is well tolerated by adult and paediatric patients during induction of anaesthesia, with a low incidence of mild airway complications (breath-holding, coughing, excitement and laryngospasm). During rapid induction, it is particularly better tolerated than isoflurane or halothane. Sevoflurane has a lower potential for hepatic injury than halothane. Unlike methoxyflurane, sevoflurane undergoes minimal intrarenal defluorination, which may account for the lack of fluoride ion-induced nephrotoxicity in humans, despite elevated plasma fluoride levels after its use. In summary, sevoflurane provides for a rapid and smooth induction of, and recovery from, anaesthesia. These features combined with its favourable cardiovascular profile should make sevoflurane the agent of choice for inhalation induction in adult and paediatric anaesthesia. Although further clinical evaluation will define the role of this agent relative to that of propofol and desflurane, sevoflurane should also prove to be a valuable alternative anaesthetic agent for adults in both outpatient and inpatient surgery.

Adolescent↗

[Sevoflurane in pediatric anesthesia. Malignant hyperthermia].

Inhalational anaesthesia is the most common anaesthesia technique in paediatric anaesthesia worldwide. Up to now the standard anaesthetic used is halothane. Because halothane is tolerated in the upper airways without side effects it is well suited for the inhalational induction of anaesthesia. However, halothane exerts side effects on the hepatic and the cardiovascular system. This review focuses on the replacement of halothane by sevoflurane in paediatric anaesthesia. Apart from its favorable pharmacological properties sevoflurane is also superior because of economical considerations. The following conclusions are drawn: (1) Halothane and sevoflurane do not cause irritations of the airways and are thus suitable for an inhalational induction. Sevoflurane should be administered in oxygen/nitrous oxide during induction of anaesthesia to reduce excitation. (2) The MAC values of sevoflurane are age dependent. In contrast to adult patients the MAC values of sevoflurane are only decreased by 20 to 25% in paediatric patients. The end-tidal concentration of sevoflurane necessary for intubation or insertion of a laryngeal mask is 2 to 4 Vol.%. (3) The blood/gas partition coefficient of sevoflurane is low, resulting in shorter induction times with sevoflurane compared to halothane. The so called priming technique with 8 Vol.% of sevoflurane results in shorter induction times. Consequently, times to recovery and psycho-motor functions are favourable for sevoflurane compared to halothane in paediatric patients. However, shorter recovery times lead to earlier perception of postoperative pain, requiring adequate pain management. (4) The hemodynamic stability after administration of sevoflurane is favourable to that after halothane in paediatric patients, leading to significantly less bradycardia. (5) In paediatric patients no negative effects on kidney function have been observed after administration of sevoflurane. There is no scientific basis for organotoxic effects, thus sevoflurane is suitable for low-flow and minimal-flow anaesthesia. (6) The duration of the action of muscle relaxants is increased to a greater extent in presence of sevoflurane compared to halothane. Consequently, the total dose of muscle relaxants can be reduced using sevoflurane. (7) Similar to the established inhalational anaesthetics sevoflurane triggers malignant hyperthermia (MH) and must not be used in patients in which MH is suspected or in which a predisposition for MH is known.

Anesthesia, Inhalation↗

Porcine systemic and regional organ blood flow during 1.0 and 1.5 minimum alveolar concentrations of sevoflurane anesthesia without and with 50% nitrous oxide.

Effects of sevoflurane anesthesia on organ blood flow were examined in nine healthy isocapnic pigs using 15-mumol diameter radionuclide-labeled microspheres that were injected into the left atrium. Minimum alveolar concentration (MAC) of sevoflurane required to prevent 50% of the pigs from responding by gross purposeful movement to a noxious stimulus was found to be 2.66 +/- 0.20%. Hemodynamic measurements were made on each pig during the following five conditions: awake (control); 1.0 MAC of sevoflurane anesthesia; 2.66% (1.0 MAC) sevoflurane + 50% N2O anesthesia; 1.5 MAC of sevoflurane anesthesia; and 3.99% (1.5 MAC) sevoflurane + 50% N2O anesthesia. Dose-related decrease in cardiac output, mean aortic pressure and left ventricular work occurred with sevoflurane anesthesia but heart rate was unchanged. Addition of 50% N2O to either of the pre-established sevoflurane concentrations did not change heart rate or the cardiac output, but with 3.99% sevoflurane mean aortic pressure decreased further. Unlike isoflurane and halothane which increase porcine brain blood flow, cerebral blood flow decreased to a similar level with both levels of sevoflurane anesthesia. Whereas cerebellar perfusion was unaltered with both levels of sevoflurane anesthesia, brain-stem blood flow decreased to a similar level from the control value. However, during 3.99% sevoflurane anesthesia, brain-stem blood flow exceeded that at 2.66% sevoflurane anesthesia. Addition of N2O to pre-established concentrations of sevoflurane increased regional brain blood flow but cerebral and brain-stem blood flow exceeded awake value only during 2.66% sevoflurane + 50% N2O anesthesia. Transmural myocardial blood flow decreased in a dose-dependent manner during sevoflurane anesthesia but the subendocardial/subepicardial perfusion ratio remained at control value.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenal Glands↗