Pharmacokinetics of desflurane, sevoflurane, isoflurane, and halothane in pigs

We tested the prediction that the alveolar washin and washout, tissue time constants, and pulmonary recovery (volume of agent recovered during washout relative to the volume taken up during washin) of desflurane, sevoflurane, isoflurane, and halothane would be defined primarily by their respective solubilities in blood, by their solubilities in tissues, and by their metabolism. We concurrently administered approximately one-third the MAC of each of these anesthetics to five young female swine and determined (separately) their solubilities in pig blood and tissues. The blood/gas partition coefficient of desflurane (0.35 +/- 0.02) was significantly smaller (P less than 0.01) than that of sevoflurane (0.45 +/- 0.02), isoflurane (0.94 +/- 0.05), and halothane (2.54 +/- 0.21). Tissue/blood partition coefficients of desflurane and halothane were smaller than those for the other two anesthetics (P less than 0.05) for all tissue groups. As predicted from their blood solubilities, the order of washin and washout was desflurane, sevoflurane, isoflurane, and halothane (most to least rapid). As predicted from tissue solubilities, the tissue time constants for desflurane were smaller than those for sevoflurane, isoflurane, and halothane. Recovery (normalized to that of isoflurane) of the volume of anesthetic taken up was significantly greater (P less than 0.05) for desflurane (93% +/- 7% [mean +/- SD]) than for halothane (77% +/- 6%), was not different from that of isoflurane (100%), but was less than that for sevoflurane (111% +/- 17%). The lower value for halothane is consistent with its known metabolism, but the lower (than sevoflurane) value for desflurane is at variance with other presently available data for their respective biodegradations.     

Solubility of desflurane (I-653), sevoflurane, isoflurane, and halothane in human blood

The blood/gas partition coefficients for the new volatile anesthetic agent desflurane (I-653), sevoflurane, isoflurane, and halothane were determined, simultaneously, in 8 human volunteers to compare the solubilities of these agents in blood. The blood/gas partition coefficient for desflurane [0.49 +/- 0.03 (mean +/- SD)] was smallest, followed by sevoflurane (0.62 +/- 0.04), isoflurane (1.27 +/- 0.06), and halothane (2.46 +/- 0.09). Differences among the anesthetic agents were significant (P less than 0.001). The results of this study confirm that among these agents the solubility of desflurane in human blood is the smallest. The results suggest that the washin and washout of desflurane will be more rapid than that of sevoflurane, isoflurane, and halothane, and the washin and washout of sevoflurane will be more rapid than that of isoflurane and halothane.     

Percutaneous loss of desflurane, isoflurane, and halothane in humans

We studied the percutaneous losses of the new inhaled anesthetic, desflurane (I-653), and of isoflurane and halothane during anesthetic administration and elimination in seven healthy male volunteers. Anesthesia was induced and maintained with midazolam, thiopental, and fentanyl. We administered 70% N2O for 30 min, and then administered 2% desflurane, 0.4% isoflurane, and 0.2% halothane concurrently with 65% N2O for 30 min. Inspired, end-tidal, and mixed-expired gas samples were collected during administration of the volatile agents and for 5-7 days of elimination. The right arm and hand of each subject was enclosed in a sealed glass cylinder having a port at each end, one for sampling and both for flushing with N2 after anesthetic administration and every 15 min thereafter. We sampled gases from the cylinder during administration and for the 150 min of elimination and analyzed their anesthetic concentrations by gas chromatography. The surface area of the enclosed portion of the arm was measured, and the total body surface area was calculated. All values were normalized to (i.e., divided by) the end-tidal (alveolar) concentration at the end of administration. During administration, percutaneous loss of halothane was 3.5 times that of desflurane and 2 times that of isoflurane. During elimination, the loss of halothane was 6 times and 2 times greater than the loss of desflurane and isoflurane, respectively. Percutaneous loss of halothane significantly exceeded that of isoflurane. The elimination values included an estimate of elimination after 150 min. The percutaneous loss of each anesthetic was 2- to 3-fold greater during elimination than administration.(ABSTRACT TRUNCATED AT 250 WORDS)     

Alteration of left ventricular diastolic function by desflurane, isoflurane, and halothane in the chronically instrumented dog with autonomic nervous system blockade

The effects of the new volatile anesthetic desflurane on three indices of left ventricular diastolic function were examined and compared to those produced by equianesthetic concentrations of isoflurane and halothane. Diastolic function has been shown to significantly influence systolic performance, but the effects of volatile anesthetics on diastolic function have not been extensively examined. Since autonomic nervous system function may significantly influence hemodynamic actions of anesthetics in vivo, experiments were performed in the presence of pharmacologic blockade of the autonomic nervous system. Three groups comprising a total of 23 experiments were performed using 11 dogs instrumented for measurement of aortic and left ventricular pressure, rate of increase of left ventricular pressure (dP/dt), subendocardial segment length, and cardiac output. Systemic hemodynamics were recorded in the conscious state and after 30 min equilibration at 1.0 and 1.5 MAC desflurane, isoflurane, or halothane. Ventricular relaxation was described using invasively derived time constants of isovolumetric relaxation with zero (To) or nonzero (Tn) assumptions of asymptotic decay. Chamber and myocardial stiffness the viscoelastic properties of the ventricle, were described using exponential relationships relating ventricular pressure to segment length and end-diastolic pressure to Lagrangian strain, respectively. Desflurane produced a significant (P less than 0.05) and dose-dependent increase in isovolumetric relaxation as a evaluated by both time constants (To, 22.2 +/- 2.0 during control to 33.9 +/- 3.5 ms at 1.5 MAC; Tn, 33.1 +/- 1.6 during control to 45.1 +/- 4.3 ms at 1.5 MAC). Similar degrees of prolongation of isovolumetric relaxation were produced by isoflurane (Tn, 35.6 +/- 1.5 during control to 47.1 +/- 2.9 ms at 1.5 MAC) and halothane (Tn, 31.7 +/- 2.2 during control to 42.3 +/- 3.9 ms at 1.5 MAC). Halothane also caused an increase in regional passive chamber stiffness (Kp, 0.46 +/- 0.07 during control to 0.88 +/- 0.17 mm-1 at 1.5 MAC) indicating a decrease in ventricular compliance. No changes in chamber stiffness were observed with desflurane or isoflurane. In addition, no significant changes in myocardial stress-strain relationships as evaluated by nonlinear elastic coefficients, alpha (gain) and beta (myocardial stiffness), were observed with any anesthetic. Although the effects of volatile anesthetics on systolic function could not be entirely excluded from the analysis, the results indicated that desflurane, isoflurane, and halothane produce equivalent degrees of prolongation of isovolumetric relaxation. Halothane also caused a decrease in compliance during passive filling as evaluated by chamber stiffness, but no change in compliance was observed at end diastole as assessed by stress-strain relationships.(ABSTRACT TRUNCATED AT 400 WORDS)     

Effects of Volatile Anesthetics on Atrial and AV Nodal Electrophysiological Properties in Guinea Pig Isolated Perfused Heart

Background: Knowledge of the anesthetic effects on atrial and atrioventricular (AV) nodal electrophysiologic properties is fundamental to understand the modulatory role of anesthetics on the pathogenesis of supraventricular tachycardias, and to individualize the perioperative management of patients with supraventricular tachycardias or AV nodal conduction disturbances. Therefore the authors studied the effects of three commonly used volatile anesthetics on the electrophysiologic properties of the atrium and AV node.

Methods: The concentration-dependent electrophysiologic effects of halothane, isoflurane, and desflurane (0 - 2 minimum alveolar concentration [MAC]) were studied in guinea pig Langendorff-perfused hearts fit with instruments to simultaneously measure atrial and AV nodal conduction times and atrial monophasic action potential duration. Atrial and AV nodal effective refractory periods were measured simultaneously using a computer-assisted premature stimulation protocol. The concentrations of anesthetics in the gas phase were monitor by an infrared gas analyzer.

Results: Volatile anesthetics caused markedly different concentration-dependent effects on atrial conduction, repolarization, and refractoriness, and on AV nodal function. At equianesthetic concentrations, halothane depressed atrial conduction the most, whereas desflurane caused the greatest shortening of atrial monophasic action potential duration. Halothane had no significant effect on atrial refractoriness, whereas at 2 MAC desflurane significantly shortened and isoflurane significantly prolonged atrial effective refractory periods by 18.1 +/- 13.5% and 13.2 +/- 14.7%, respectively. On an equi-MAC basis, the rank order of potency for the anesthetics to prolong AV nodal conduction time and AV nodal ERP was halothane > desflurane > isoflurane.     

Comparison of the systemic and coronary hemodynamic actions of desflurane, isoflurane, halothane, and enflurane in the chronically instrumented dog

The systemic and coronary hemodynamic effects of desflurane were compared to those of isoflurane, halothane, and enflurane in chronically instrumented dogs. Since autonomic nervous system function may significantly influence the hemodynamic actions of anesthetics in vivo, a series of experiments also was performed in the presence of pharmacologic blockade of the autonomic nervous system. Eight groups comprising a total of 80 experiments were performed on 10 dogs instrumented for measurement of aortic and left ventricular pressure, the peak rate of increase of left ventricular pressure (dP/dt), subendocardial segment length, coronary blood flow velocity, and cardiac output. Systemic and coronary hemodynamics were recorded in the conscious state and after 30 min equilibration at 1.25 and 1.75 MAC desflurane, isoflurane, halothane, and enflurane. Desflurane (+79 +/- 12% change from control) produced greater increases in heart rate than did halothane (+44 +/- 12% change from control) or enflurane (+44 +/- 9% change from control) at 1.75 MAC. Desflurane preserved mean arterial pressure to a greater degree than did equianesthetic concentrations of isoflurane. This result was attributed to a smaller effect on peripheral vascular resistance as compared to isoflurane and greater preservation of myocardial contractility as evaluated by peak positive left ventricular dP/dt and the rate of increase of ventricular pressure at 50 mmHg (dP/dt50) compared to other volatile anesthetics. Increases in diastolic coronary blood flow velocity (+19 +/- 6 and +35 +/- 12% change from control at 1.75 MAC, respectively) and concomitant decreases in diastolic coronary vascular resistance (-41 +/- 12 and -58 +/- 6% change from control at 1.75 MAC, respectively) were produced by desflurane and isoflurane. In the presence of autonomic nervous system blockade, the actions of desflurane and isoflurane were nearly identical with the exception of coronary vasodilation. After autonomic nervous system blockade, isoflurane increased coronary blood flow velocity, but desflurane did not. Furthermore, both desflurane and isoflurane continued to produce less depression of myocardial contractility than did halothane and enflurane. In summary, at equianesthetic concentrations, desflurane and isoflurane produced similar hemodynamic effects; however, in the absence of drugs that inhibit autonomic reflexes, desflurane had less negative inotropic activity and produced less decrease in arterial pressure. The coronary vasodilator actions of desflurane and isoflurane within the limitations of this model were not similar. When the increase in heart rate and rate-pressure product produced by desflurane were prevented in dogs with autonomic nervous system blockade, desflurane produced no change in coronary blood flow velocity.     

The extent of metabolism of inhaled anesthetics in humans

To determine the percentage of anesthetic metabolized and to assess the role of metabolism in the total elimination of inhaled anesthetics, the authors administered isoflurane, enflurane, halothane, and methoxyflurane simultaneously, for 2 h, to nine healthy patients. Total anesthetic uptake during the 2 h of washin and total recovery of unchanged anesthetic in exhaled gases during 5 to 9 days of washout were measured, and from these the per cent of anesthetic uptake that was recovered was calculated. Of the isoflurane taken up, 93 +/- 4% (mean +/- SE) was recovered. To compensate for factors other than metabolism that limit complete recovery of unchanged anesthetic, the percentage recovery of each anesthetic was normalized to the percentage recovery of isoflurane (which it was assumed undergoes no metabolism). Deficits in normalized recovery were assumed to be due to metabolism of the anesthetics. The resulting estimates of metabolism of anesthetic taken up were: enflurane 8.5 +/- 1.0%, halothane 46.1 +/- 0.9%, and methoxyflurane 75.3 +/- 1.6%. These results indicate that elimination is primarily via the lungs for isoflurane and enflurane, equally via the lungs and via metabolism for halothane, and primarily via metabolism for methoxyflurane.     

Changing from Isoflurane to Desflurane toward the End of Anesthesia Does Not Accelerate Recovery in Humans

Background: In an attempt to combine the advantage of the lower solubilities of new inhaled anesthetics with the lesser cost of older anesthetics, some clinicians substitute the former for the latter toward the end of anesthesia. The authors tried to determine whether substituting desflurane for isoflurane in the last 30 min of a 120-min anesthetic would accelerate recovery.

Methods: Five volunteers were anesthetized three times for 2 h using a fresh gas inflow of 2 l/min: 1.25 minimum alveolar concentration (MAC) desflurane, 1.25 MAC isoflurane, and 1.25 MAC isoflurane for 90 min followed by 30 min of desflurane concentrations sufficient to achieve a total of 1.25 MAC equivalent ("crossover"). Recovery from anesthesia was assessed by the time to respond to commands, by orientation, and by tests of cognitive function.

Results: Compared with isoflurane, the crossover technique did not accelerate early or late recovery (P > 0.05). Recovery from isoflurane or the crossover anesthetic was significantly longer than after desflurane (P < 0.05). Times to response to commands for isoflurane, the crossover anesthetic, and desflurane were 23 +/- 5 min (mean +/- SD), 21 +/- 5 min, and 11 +/- 1 min, respectively, and to orientation the times were 27 +/- 7 min, 25 +/- 5 min, and 13 +/- 2 min, respectively. Cognitive test performance returned to reference values 15-30 min sooner after desflurane than after isoflurane or the crossover anesthetic. Isoflurane cognitive test performance did not differ from that with the crossover anesthetic at any time.     

The efficacy and safety of intravenous emulsified isoflurane in rats

Although direct IV injection of liquid volatile anesthetics is usually lethal, anesthesia using emulsified halothane and isoflurane without adverse effects has been safely induced in animals. We identified the safe concentration of emulsified volatile anesthetic preparations and determined the dose-response relationship of IV emulsified isoflurane and propofol in rats. Liquid/gas partition coefficients of desflurane, sevoflurane, isoflurane, enflurane, and halothane in 20% and 30% Intralipid were measured and used to calculate their saturated concentrations. Unsaturated emulsified isoflurane was prepared by adding liquid isoflurane to 30% Intralipid. The loss of forepaw righting reflex was taken as induction of anesthesia, and disappearance of electrocardiogram was taken as death. The median effective induction dose (ED50) and median lethal dose (LD50) of emulsified isoflurane were 0.072 and 0.216 mL/kg liquid isoflurane, respectively. The ED50 and LD50 of propofol were 5.89 mg/kg and 18.19 mg/kg, respectively. Time to return of forepaw righting reflex after injection of emulsified isoflurane (38 +/- 18 s) was significantly shorter than with propofol (101 +/- 62 s; P < 0.05). Anesthesia was successfully induced in rats by IV emulsified isoflurane with a comparable safety index and certain safety factor as propofol. Recovery of anesthesia after IV emulsified isoflurane was faster than with propofol.     

Minimum alveolar anesthetic concentration of volatile anesthetics in normal and cardiomyopathic hamsters

Minimum alveolar anesthetic concentrations (MAC) values of volatile anesthetics in cardiovascular diseases remain unknown. We determined MAC values of volatile anesthetics in spontaneously breathing normal and cardiomyopathic hamsters exposed to increasing (0.1%-0.3% steps) concentrations of halothane, isoflurane, sevoflurane, or desflurane (n = 30 in each group) using the tail-clamp technique. MAC values and their 95% confidence interval were calculated using logistic regression. In normal hamsters, inspired MAC values were: halothane 1.15% (1.10%-1.20%), isoflurane 1.62% (1.54%-1.69%), sevoflurane 2.31% (2.22%-2.40%), and desflurane 7.48% (7.30%-7.67%). In cardiomyopathic hamsters, they were: halothane 0.89% (0.83%-0.95%), isoflurane 1.39% (1.30%-1.47%), sevoflurane 2.00% (1.85%-2.15%), and desflurane 6.97% (6.77%-7.17%). Thus, MAC values of halothane, isoflurane, sevoflurane, and desflurane were reduced by 23% (P < 0.05), 14% (P < 0.05), 13% (P < 0.05), and 7% (P < 0.05), respectively in cardiomyopathic hamsters. IMPLICATIONS: Minimum alveolar anesthetic concentrations of volatile anesthetics were significantly lower in cardiomyopathic hamsters than in normal hamsters.     

A comparison of desflurane and isoflurane in patients undergoing coronary artery surgery

Animal studies indicate that desflurane and isoflurane have similar hemodynamic effects when administered in equipotent anesthetic concentrations. The authors compared desflurane and isoflurane, used as primary anesthetics for patients undergoing elective coronary artery bypass surgery whose left ventricular ejection fractions were greater than 0.34. After induction of anesthesia with thiopental (dose 180 +/- 45 mg [mean +/- standard deviation]) and fentanyl, 10 micrograms.kg-1, either desflurane or isoflurane was administered to maintain systolic blood pressure within 70-120% of, and heart rates less than 120% of, the patients' average preoperative values. If adjusting the end-tidal anesthetic concentration within the range of 0-2.0 MAC could not maintain these predefined hemodynamic limits, additional fentanyl or vasoactive drugs were used. Induction and maintenance of anesthesia was accompanied by a significant decrease in mean arterial pressure in both groups (desflurane 97 +/- 12 mmHg at control, decreasing to 71 +/- 5 mmHg during skin preparation; isoflurane 95 +/- 9 mmHg at control, 74 +/- 9 mmHg during skin preparation). One minute after sternotomy, mean arterial pressure in the isoflurane group had returned to control, 97 +/- 9 mmHg, which was significantly greater than in the desflurane group, 87 +/- 12 mmHg. Systolic arterial pressure was also significantly greater in the isoflurane group 1 min after intubation, during skin preparation, and 1 min after sternotomy. Otherwise, the hemodynamic effects of these volatile agents were similar. There were no differences between groups in the incidence of ECG changes indicative of myocardial ischemia prior to cardiopulmonary bypass, perioperative myocardial infarction, or perioperative mortality.(ABSTRACT TRUNCATED AT 250 WORDS)     

Immediate anesthesia recovery and psychomotor function of patient after prolonged anesthesia with desflurane, sevoflurane or isoflurane

OBJECTIVE: To compare the anesthetic maintenance and early postoperative recovery and psychomotor function in patients who have been anesthestized with desflurane, sevoflurane or isoflurane during prolonged open urological surgery. PATIENTS AND METHODS: Seventy-five patients were randomly assigned to receive desflurane, sevoflurane or isoflurane with N2O 60% for anesthetic maintenance. The concentration of each drug was adjusted to maintain arterial pressure and heart rate +/- 20% of baseline. After the operation the anesthetics were discontinued and times until eye opening, spontaneous breathing, extubation and orientation were recorded. In the post-anesthesia recovery ward we applied the Newman-Trieger and Aldrete tests and recorded instances of nausea and vomiting and need for analgesia during the first 24 hours after surgery. RESULTS: The groups were similar with regard to demographic features, anesthetic maintenance, duration of anesthesia and relative doses of the anesthetics used. Recovery times in the operating room were significantly shorter (p < 0.05) after anesthesia with desflurane and sevoflurane than with isoflurane, with no significant differences between the desflurane and sevoflurane groups (duration of anesthesia 198 +/- 90, 171 +/- 67 and 191 +/- 79; eye opening 7.6 +/- 3.7, 7.8 +/- 3.0 and 11.9 +/- 4.5; time until extubation 7.8 +/- 3.0, 8.3 +/- 3.0 and 11.0 +/- 3.5 for desflurane, sevoflurane and isoflurane, respectively; all data in minutes). Recovery in the post-anesthetic recovery ward was similar for all three groups. CONCLUSIONS: Anesthetic maintenance was comparable with all three drugs. Desflurane and sevoflurane demonstrated advantages over isoflurane during recovery from anesthesia in the operating theater. No significant differences were found in psychomotor recovery, nausea and/or vomiting or requirements for postoperative analgesia.     

Volatile anesthetics enhance flash-induced gamma oscillations in rat visual cortex

BACKGROUND: The authors sought to understand neural correlates of anesthetic-induced unconsciousness. Cortical gamma oscillations have been associated with neural processes supporting conscious perception, but the effect of general anesthesia on these oscillations is controversial. In this study, the authors examined three volatile anesthetics, halothane, isoflurane, and desflurane, and compared their effects on flash-induced gamma oscillations in terms of equivalent concentrations producing the loss of righting reflex (1 minimum alveolar concentration for the loss of righting [MAC(LR)]). METHODS: Light flashes were presented every 5 s for 5 min, and event-related potentials were recorded from primary visual cortex of 15 rats with a chronically implanted bipolar electrode at increasing anesthetic concentrations (0-2.4 MAC(LR)). Early cortical response was obtained by averaging poststimulus (0-100 ms) potentials filtered at 20-60 Hz across 60 trials. Late (100-1,000 ms) gamma power was calculated using multitaper power spectral technique. Wavelet decomposition was used to determine spectral and temporal distributions of gamma power. RESULTS: The authors found that (1) halothane, isoflurane, and desflurane enhanced the flash-evoked early cortical response in a concentration-dependent manner; (2) the effective concentration for this enhancement was the lowest for isoflurane, intermediate for halothane, and the highest for desflurane when compared at equal fractions of the concentration that led to a loss of righting; (3) the power of flash-induced late (> 100 ms) gamma oscillations was augmented at intermediate concentrations of all three anesthetic agents; and (4) flash-induced gamma power was not reduced below waking baseline even in deep anesthesia. CONCLUSIONS: These findings suggest that a reduction in flash-induced gamma oscillations in rat visual cortex is not a unitary correlate of anesthetic-induced unconsciousness.     

Comparison of enflurane, halothane, and isoflurane for diagnostic and therapeutic procedures in children with malignancies

The authors performed a randomized, prospective trial comparing enflurane, halothane, and isoflurane (each administered with nitrous oxide) to establish which inhaled anesthetic produced the fewest complications and the most rapid induction of anesthesia for children undergoing general anesthesia for diagnostic procedures as oncology outpatients. Sixty-six children, ranging from 8 months to 18 years, underwent a total of 124 anesthetics. Induction of anesthesia (time from placement of facemask to beginning of skin preparation) was faster with halothane (2.7 +/- 1.0 min, mean +/- SD, n = 46) than with enflurane (3.2 +/- 0.8 min, n = 43) or isoflurane (3.3 +/- 1.2 min, n = 35). Emergence from anesthesia (time from completion of the procedure to spontaneous eye opening) was more rapid with enflurane (4.7 +/- 4.4 min) than with halothane (6.2 +/- 4.5 min) or isoflurane (6.2 +/- 3.9 min). Total time from the start of procedure until discharge was longer with isoflurane (25.1 +/- 6.8 min) than with enflurane (21.5 +/- 8.6 min) or halothane (22.3 +/- 7.6 min). During induction, the incidence of laryngospasm was greatest with isoflurane (23%) and the incidence of excitement least with halothane (13%). During the maintenance of, emergence from, and recovery from anesthesia, coughing occurred most frequently with isoflurane. During the recovery period, headache occurred most frequently with halothane (9%); there were no significant differences in the incidence of nausea, vomiting, hunger, or depressed effect. The authors conclude that the rapid induction and minimal airway-related complications associated with halothane anesthesia make it an excellent anesthetic agent for pediatric patients undergoing short diagnostic procedures.     

Low-flow anesthesia and reduced animal size increase carboxyhemoglobin levels in swine during desflurane and isoflurane breakdown in dried soda lime

After institutional approval, we studied the effect of animal size, anesthetic concentration, and fresh gas flow (FGF) rate on inspired carbon monoxide (CO) and carboxyhemoglobin (COHb) during anesthesia in swine, using soda lime previously dried to 1 +/- 0.1% water content. To ascertain the effect of anesthesia, eight adult pigs were anesthetized with either 1 minimum alveolar anesthetic concentration (MAC) desflurane or isoflurane and, to characterize the effect of the FGF rate, it was doubled in four pigs. To determine the effect of animal size, four small and four large pigs received 1 MAC desflurane or isoflurane, and to determine the effect of the anesthetic concentration, a group of four swine was exposed to 0.5 MAC. CO and COHb concentrations were larger with desflurane (5500 +/- 980 ppm and 57.90% +/- 0.50%, respectively) than with isoflurane (800 ppm and 17.8% +/- 2.14%, respectively), especially in the small animals. Increasing the FGF rate significantly reduced peak CO and COHb concentrations resulting from both anesthetics; however, when each anesthetic was reduced to 0.5 MAC, the concentrations obtained were similar. We conclude that CO intoxication is more severe with desflurane than with isoflurane, that small animals are at higher risk for CO poisoning, and that low FGF can increase COHb concentrations. IMPLICATIONS: The present study shows that the use of desflurane with desiccated carbon dioxide absorbents in pediatric anesthesia can produce a dangerous carbon dioxide intoxication, especially with low-flow anesthesia.     

Mechanistic Aspects of Carbon Monoxide Formation from Volatile Anesthetics

Background: Desflurane, enflurane and isoflurane can be degraded to carbon monoxide (CO) by carbon dioxide absorbents, whereas sevoflurane and halothane form negligible amounts of CO. Carbon monoxide formation is greater with drier absorbent, and with barium hydroxide, than with soda lime. The mechanism, role of absorbent composition and water, and anesthetic structures determining CO formation are unknown. This investigation examined sequential steps in anesthetic degradation to CO.

Methods: Carbon monoxide formation from anesthetics and desiccated barium hydroxide lime or soda lime was determined at equimole from deuterium-substituted anesthetics was also quantified. Proton abstraction from anesthetics by strong base was determined by deuterium isotope exchange. A reactive chemical intermediate was trapped and identified by gas chromatography-mass spectrometry. The source of the oxygen in CO was identified by18 O incorporation.

Results: Desflurane, enflurane, and isoflurane (difluoromethylethyl ethers), but not sevoflurane (monofluoromethyl ether), methoxyflurane (methyl-ethyl ether), or halothane (alkane) were degraded to CO. The amount of CO formed was desflurane >or= to enflurane > isoflurane at equiMAC and enflurane > desflurane > isoflurane at equimole concentrations. Proton abstraction from the difluoromethoxy carbon was greater with potassium than with sodium hydroxide, but unmeasurable with barium hydroxide. Carbon monoxide formation was correlated (r = 0.95-1.00) with difluoromethoxy (enflurane > desflurane > isoflurane >or= to methoxyflurane = sevoflurane = 0) but not ethyl carbon proton abstraction. Deuterium substitution on enflurane and desflurane diminished CO formation. Chemical trapping showed formation of a difluorocarbene intermediate from enflurane and desflurane. Incorporation of H218 O in barium hydroxide lime resulted in C18 O formation from unlabeled enflurane and desflurane.     

Carbon Monoxide Production from Desflurane, Enflurane, Halothane, Isoflurane, and Sevoflurane with Dry Soda Lime

Background : Previous studies in which volatile anesthetics were exposed to small amounts of dry soda lime, generally controlled at or close to ambient temperatures, have demonstrated a large carbon monoxide (CO) production from desflurane and enflurane, less from isoflurane, and none from halothane and sevoflurane. However, there is a report of increased CO hemoglobin in children who had been induced with sevoflurane that had passed through dry soda lime. Because this clinical report appears to be inconsistent with existing laboratory work, the authors investigated CO production from volatile anesthetics more realistically simulating conditions in clinical absorbers.

Methods : Each agent, 2.5 or 5% in 2 l/min oxygen, were passed for 2 h through a Drager absorber canister (bottom to top) filled with dried soda lime (Dragersorb 800). CO concentrations were continuously measured at the absorber outlet. CO production was calculated. Experiments were performed in ambient air (19-20[degrees]C). The absorbent temperature was not controlled.

Results : Carbon monoxide production peaked initially and was highest with desflurane (507 +/- 70, 656 +/- 59 ml CO), followed by enflurane (460 +/- 41, 475 +/- 99 ml CO), isoflurane (176 +/- 2.8, 227 +/- 21 ml CO), sevoflurane (34 +/- 1, 104 +/- 4 ml CO), and halothane (22 +/- 3, 20 +/- 1 ml CO) (mean +/- SD at 2.5 and 5%, respectively).     

Carbon monoxide production from desflurane, enflurane, halothane, isoflurane, and sevoflurane with dry soda lime.

BACKGROUND: Previous studies in which volatile anesthetics were exposed to small amounts of dry soda lime, generally controlled at or close to ambient temperatures, have demonstrated a large carbon monoxide (CO) production from desflurane and enflurane, less from isoflurane, and none from halothane and sevoflurane. However, there is a report of increased CO hemoglobin in children who had been induced with sevoflurane that had passed through dry soda lime. Because this clinical report appears to be inconsistent with existing laboratory work, the authors investigated CO production from volatile anesthetics more realistically simulating conditions in clinical absorbers. METHODS: Each agent, 2.5 or 5% in 2 l/min oxygen, were passed for 2 h through a Dr?ger absorber canister (bottom to top) filled with dried soda lime (Dr?gersorb 800). CO concentrations were continuously measured at the absorber outlet. CO production was calculated. Experiments were performed in ambient air (19-20 degrees C). The absorbent temperature was not controlled. RESULTS: Carbon monoxide production peaked initially and was highest with desflurane (507 +/- 70, 656 +/- 59 ml CO), followed by enflurane (460 +/- 41, 475 +/- 99 ml CO), isoflurane (176 +/- 2.8, 227 +/- 21 ml CO), sevoflurane (34 +/- 1, 104 +/- 4 ml CO), and halothane (22 +/- 3, 20 +/- 1 ml CO) (mean +/- SD at 2.5 and 5%, respectively). CONCLUSIONS: The absorbent temperature increased with all anesthetics but was highest for sevoflurane. The reported magnitude of CO formation from desflurane, enflurane, and isoflurane was confirmed. In contrast, a smaller but significant CO formation from sevoflurane was found, which may account for the CO hemoglobin concentrations reported in infants. With all agents, CO formation appears to be self-limited.     

Comparative Pharmacodynamic Modeling of the Electroencephalography-slowing Effect of Isoflurane, Sevoflurane, and Desflurane

Background: The most common measure to compare potencies of volatile anesthetics is minimum alveolar concentration (MAC), although this value describes only a single point on a quantal concentration-response curve and most likely reflects more the effects on the spinal cord rather than on the brain. To obtain more complete concentration-response curves for the cerebral effects of isoflurane, sevoflurane, and desflurane, the authors used the spectral edge frequency at the 95th percentile of the power spectrum (SEF95) as a measure of cerebral effect.

Methods: Thirty-nine patients were randomized to isoflurane, sevoflurane, or desflurane groups. After induction with propofol, intubation, and a waiting period, end-tidal anesthetic concentrations were randomly varied between 0.6 and 1.3 MAC, and the EEG was recorded continuously. Population pharmacodynamic modeling was performed using the software package NONMEM.

Results: The population mean EC50 values of the final model for SEF (95) suppression were 0.66 +/- 0.08 (+/- SE of estimate) vol% for isoflurane, 1.18 +/- 0.10 vol% for sevoflurane, and 3.48 +/- 0.66 vol% for desflurane. The slopes of the concentration-response curves were not significantly different; the common value was [Greek small letter lambda] = 0.86 +/- 0.06. The Ke0 value was significantly higher for desflurane (0.61 +/- 0.11 min-1), whereas separate values for isoflurane and sevoflurane yielded no better fit than the common value of 0.29 +/- 0.04 min (-1). When concentration data were converted into fractions of the respective MAC values, no significant difference of the C50 values for the three anesthetic agents was found.     

The anticonvulsant effects of volatile anesthetics on penicillin-induced status epilepticus in cats

Volatile anesthetics may be used to treat status epilepticus when conventional drugs are ineffective. We studied 30 cats to compare the inhibitory effects of sevoflurane, isoflurane, and halothane on penicillin-induced status epilepticus. Anesthesia was induced and maintained with one of the three volatile anesthetics in oxygen. Penicillin G was injected into the cisterna magna, and the volatile anesthetic discontinued. Once status epilepticus was induced (convulsive period), the animal was reanesthetized with 0.6 minimum alveolar anesthetic concentration (MAC) of the volatile anesthetic for 30 min, then with 1.5 MAC for the next 30 min. Electroencephalogram and multiunit activity in the midbrain reticular formation were recorded. At 0.6 MAC, all anesthetics showed anticonvulsant effects. Isoflurane and halothane each abolished the repetitive spike phase in one cat; isoflurane reduced the occupancy of the repetitive spike phase (to 27%+/-22% of the convulsive period (mean +/- SD) significantly more than sevoflurane (60%+/-29%; P < 0.05) and halothane (61%+/-24%; P < 0.05), and the increase of midbrain reticular formation with repetitive spikes was reduced by all volatile anesthetics. The repetitive spikes were abolished by 1.5 MAC of the anesthetics: in 9 of 10 cats by sevoflurane, in 9 of 9 cats by isoflurane, and in 9 of 11 cats by halothane. In conclusion, isoflurane, sevoflurane, and halothane inhibited penicillin-induced status epilepticus, but isoflurane was the most potent. IMPLICATIONS: Convulsive status epilepticus is an emergency state and requires immediate suppression of clinical and electrical seizures, but conventional drugs may be ineffective. In such cases, general anesthesia may be effective. In the present study, we suggest that isoflurane is preferable to halothane and sevoflurane to suppress sustained seizure.