Vecuronium-induced neuromuscular blockade during enflurane, isoflurane, and halothane anesthesia in humans

To determine the effect of the commonly used volatile anesthetics on a vecuronium-induced neuromuscular blockade, the authors studied 54 patients anesthetized with 1.2 MAC or 2.2 MAC enflurane, isoflurane, or halothane (MAC value includes contribution from 60% nitrous oxide). During 1.2 MAC enflurane, isoflurane, and halothane, the ED50S (the doses depressing twitch tension 50%) for vecuronium were 12.8, 14.7, and 16.9 micrograms/kg, respectively. During 2.2 MAC enflurane, isoflurane, and halothane, the ED50S for vecuronium were 6.3, 9.8, and 13.8 micrograms/kg, respectively (P less than 0.05). Time from injection to peak effect was the same for each anesthetic group (6.5 +/- 0.5 min, mean +/- SD), except for the group given 2.2 MAC enflurane (9.7 +/- 0.6 min) (P less than 0.05). The duration of a 50% block from injection to 90% recovery was the same for each group (mean 20 +/- 4 min), except for the group given 2.2 MAC enflurane (46.5 min) (P less than 0.05). The authors conclude that enflurane is the most potent volatile anesthetic, followed by isoflurane and then halothane, in augmenting a vecuronium-induced neuromuscular blockade. Increasing the concentration of volatile anesthetic has less effect on a neuromuscular blockade produced by vecuronium than on one produced by other nondepolarizing relaxants (e.g., pancuronium and d-tubucurarine).     

Complaints in the postoperative phase related to anesthetics

In two prospective, randomized studies the frequency of headache, nausea, vomiting, and analgesic requirement during the first postoperative 24 h was observed in order to study differences between the sexes and the inhalation anesthetics halothane, enflurane, isoflurane, or balanced anesthesia with enflurane/alfentanil. Nausea and vomiting were more frequent after enflurane than after halothane or isoflurane. There was no significant difference between anesthetics and frequency of headache, but there were significant differences in postoperative analgesic requirements which were highest after halothane and lowest after isoflurane. Postoperative complaints were always significantly greater among women than among men. The second study indicated that balanced anesthesia did not reduce the analgesic requirement compared to enflurane without alfentanil, but lead to a higher incidence of vomiting. After premedication with flunitrazepam and atropine and combined with 70% N2O/30% O2, isoflurane was the most favorable anesthetic agent with regard to the parameters studied. Balanced anesthesia with enflurane/alfentanil did not show any advantages for patients in the postoperative phase under the given conditions.     

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.     

Cardiovascular responses to acute loading with nifedipine alone and nifedipine plus propranolol during inhalation anesthesia in monkeys

The cardiovascular effects of the administration of nifedipine and nifedipine combined with propranolol were examined in 15 monkeys during 0.75 and 1.25 MAC of anesthesia with isoflurane, enflurane, or halothane. Hemodynamic variables measured included heart rate (HR), mean arterial pressure (MAP), left ventricular end-diastolic pressure (LVEDP), maximum rate of increase of the Left ventricular pressure (max LV dP/dt), and thermodilution cardiac output (CO). The infusion of nifedipine at a rate adequate to produce therapeutic blood levels during 0.75 MAC with each anesthetic decreased MAP and SVR, but had no effect on cardiac index (CI), max LV dP/dt, or HR. Increasing the anesthetic concentration from 0.75 to 1.25 MAC during nifedipine administration decreased HR and MAP in all groups and decreased CI with halothane and enflurane, but not with isoflurane. Addition of propranolol by infusion in amounts adequate to produce 75% beta-adrenergic blockade caused a further depression of CI, max LV dP/dt, HR, and MAP. However, the hemodynamic depression was significantly greater with halothane and enflurane than with isoflurane. Intravenous administration of calcium chloride (10 mg/kg) after calcium channel and beta-adrenergic blockade only partially reversed the hemodynamic depression that occurred with all three anesthetics. It was concluded that acute loading with nifedipine with and without propranolol exerts a greater cardiovascular depressant effect during enflurane or halothane anesthesia than during isoflurane anesthesia. The myocardial depressant effects of nifedipine and propranolol myocardial depressant effects of nifedipine and propranolol may be synergistic with the depressant effects of potent inhalation anesthetics.     

Comparison of the effects of volatile anesthetics on brain glucose metabolism in rats

The objective of this investigation was to compare the effects of the commonly used volatile anesthetics on concentrations of plasma and cerebral glucose and cerebral intermediary metabolites. Fasted male Long-Evans rats were anesthetized with a volatile anesthetic and, after tracheostomy and paralysis, were mechanically ventilated. Each of three groups received one MAC concentration of anesthesia with halothane, enflurane, or isoflurane. At the end of 60-75 min of anesthesia, blood was sampled for arterial blood gas and plasma glucose analysis, and the brain was rapidly sampled and frozen for analysis of energy metabolites. Physiologic variables were maintained as follows: PaCO2 30-40 mmHg, pHa 7.20-7.40, PaO2 greater than 60 mmHg, MAP greater than 60 mmHg, and rectal temperature 37.5-38.5 degrees C. Mean plasma glucose concentrations in the three groups were as follows (muMol/ml +/- SEM): halothane, 7.45 /- .62; enflurane, 6.95 +/- .22; isoflurane, 10.11 +/- 1.00. Mean brain glucose concentrations in the three groups were (muMol/gm wet weight): halothane, 2.04 +/- .20; enflurane, 2.07 +/- .26; isoflurane, 3.04 +/- .31. Plasma and brain glucose levels were significantly increased in the isoflurane group compared to the other two groups (P less than .05) with no differences occurring in the brain/plasma glucose ratio among the three groups. No differences were present between groups in brain lactate, pyruvate, fructose diphosphate, malate, alpha-ketoglutarate, phosphocreatine, or adenine nucleotides. Thus, at one MAC concentration, major differences between volatile anesthetics on brain energy availability are not present, although isoflurane raised cerebral glucose levels.     

Volatile anesthetics excite mammalian nociceptor afferents recorded in vitro

The present study investigated the actions of halothane, isoflurane, and enflurane on spontaneous discharge and evoked action potential activity in mammalian A-delta and C fiber nociceptors from the in vitro rabbit cornea. At 1 MAC halothane, isoflurane, and enflurane significantly (P less than 0.001) increased spontaneous discharge frequency of C fibers to 410%, 388%, and 569% of control, respectively. The anesthetics produced burst discharge activity over the concentration range of 0.25-1.5 MAC and depressed discharge activity at higher concentrations (greater than 3.0 MAC). Similar excitatory effects were produced by the potassium channel blocker 4-aminopyridine (250-500 microM). Variable effects on evoked discharge activity of A-delta fibers were observed. Halothane reduced action potential amplitude (77.3 +/- 4.5% of control +/- SD; n = 6 at 1 MAC) and increased spike latency (0.42 +/- 0.075 ms). In contrast, the ethers decreased both spike latency (isoflurane by 0.31 +/- 0.064 ms and enflurane by 0.35 +/- 0.058 ms) and action potential amplitude. Halothane and the ether anesthetics produced a common excitatory action on C fibers; however, the differential depressant effects on A-delta fibers suggest that different membrane mechanisms of action are involved.     

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.     

The effects of sevoflurane, halothane, enflurane, and isoflurane on hepatic blood flow and oxygenation in chronically instrumented greyhound dogs.

Inhalational anesthetics produce differential effects on hepatic blood flow and oxygenation that may impact hepatocellular function and drug clearance. In this investigation, the effects of sevoflurane on hepatic blood flow and oxygenation were compared with those of enflurane, halothane, and isoflurane in ten chronically instrumented greyhound dogs. Each dog randomly received enflurane, halothane, isoflurane, and sevoflurane, each at 1.0, 1.5, and 2.0 MAC concentrations. Mean arterial blood pressure and cardiac output decreased in a dose-dependent fashion during all four anesthetics studied. Heart rate increased compared to control during enflurane, isoflurane, and sevoflurane anesthesia and did not change during halothane anesthesia. Hepatic arterial blood flow and portal venous blood flow were measured by chronically implanted electromagnetic flow probes. Hepatic O2 delivery and consumption were calculated after hepatic arterial, portal venous, and hepatic venous blood gas analysis. Hepatic arterial blood flow was maintained with sevoflurane and isoflurane. Halothane and enflurane reduced hepatic arterial blood flow during all anesthetic levels compared to control (P less than 0.05), with marked reductions occurring with 1.5 and 2.0 MAC halothane concomitant with an increase in hepatic arterial vascular resistance. Portal venous blood flow was reduced with isoflurane and sevoflurane at 1.5 and 2.0 MAC. A somewhat greater reduction in portal venous blood flow occurred during 2.0 MAC sevoflurane (P less than 0.05 compared to control and 1.0 MAC values for sevoflurane). Enflurane reduced portal venous blood flow at 1.0, 1.5, and 2.0 MAC compared to control. Halothane produced the greatest reduction in portal venous blood flow (P less than 0.05 compared to sevoflurane).(ABSTRACT TRUNCATED AT 250 WORDS)     

Decrease in dose requirement of d-tubocurarine by volatile anesthetics.

Volatile anesthetics are known to decrease the requirements for neuromuscular blocking agents. To obtain a quantitative measure of the extent of this drug interaction, studies were performed on isolated guinea pig nerve--lumbrical muscle preparations exposed to methoxyflurane, halothane, isoflurane, diethyl ether, fluroxene, and enflurane in concentrations equal to MAC. From the relationship between indirect twitch height and d-tubocurarine concentration, the concentration depressing the twitch height by 50 per cent was determined. In the presence of MAC levels of anesthetic, the ED50 was decreased by the following fractional amounts: methoxyflurane, 0.311; halothane, 0.334; isoflurane, 0.335; diethyl ether, 0.462; fluroxene, 0.580; enflurane, 0.697. Comparison of the fractional decrease of d-tubocurarine dose requirement by an anesthetic at MAC and previously obtained values for the fractional depression of end-plate depolarization by an anesthetic at MAC showed that the more the anesthetic depresses depolarization, the smaller the d-tubocurarine dose requirement. Thus, clinically observed decreases in dose requirements may be explained by the effects of the anesthetics on chemosensitivity of the end-plate region.     

Closed-loop infusion of atracurium with four different anesthetic techniques

A new proportional-integral-derivative (PID) controller for the automated closed-loop delivery of atracurium was tested in 32 patients. Groups of 8 patients received halothane, enflurane, isoflurane, or N2O/morphine anesthesia. After induction of anesthesia with sodium thiopental 3-5 mg.kg-1, a bolus of atracurium 0.2 mg.kg-1 was delivered by the controller; this was followed by an infusion calculated by the controller to maintain the electromyogram (EMG) at a setpoint of 90% neuromuscular blockade. The average overshoot for the controller was 10.1% and the mean steady-state error 3.0%. The mean infusion rates for atracurium to maintain 90% blockade were calculated for each anesthetic group, with the inhalation anesthetics at 1 MAC. Infusion rates for N2O/morphine, halothane 0.8%, enflurane 1.7%, and isoflurane 1.4% at 90% blockade were 5.7 +/- 0.6, 4.9 +/- 0.3, 3.5 +/- 0.3, and 4.1 +/- 0.5 micrograms.kg-1.min-1, respectively (mean +/- SE). The infusion rate for atracurium at 90% blockade under N2O/morphine anesthesia was in general agreement with published values. The other infusion rates at 90% blockade have not been reported previously, but correspond to the known potencies of these inhalation anesthetics for augmentation of neuromuscular blockade. This controller performed well in comparison to previously developed controllers, and in addition was used as a research tool for rapid estimation of infusion rates.     

Effects of halothane, enflurane, and isoflurane on coronary blood flow autoregulation and coronary vascular reserve in the canine heart

To investigate the effects of volatile anesthetics on coronary blood flow (CBF) autoregulation and coronary vascular reserve, studies were performed on chronically instrumented dogs, awake and during the administration of 1.0 MAC halothane, enflurane, and isoflurane. Coronary pressure-flow plots were generated by measuring left anterior descending coronary artery blood flow while varying coronary inflow pressure with a hydraulic occluder. Autoregulation was quantitated by two measures: the slope of the horizontal "autoregulated" portion of the pressure-flow relationship and the autoregulation index (ArI) of Norris. Slope values (ml.min-1.mmHg-1 +/- SD) were: awake, 0.243 +/- 0.043; halothane, 0.414 +/- 0.044; enflurane, 0.587 +/- 0.187; and isoflurane, 0.795 +/- 0.246. The increase in slope was statistically significant only for halothane and isoflurane (P less than .05). The ArI approaches 1.0 when autoregulation is perfect, and approaches zero or is a negative number when autoregulation is absent. The authors found ArI values of: awake, 0.55; halothane, -0.08; enflurane, -0.01; isoflurane, -0.02. These values indicate good autoregulation while awake, but impaired autoregulation with all three anesthetics (P less than .05). Coronary vascular reserve was calculated, at a diastolic coronary pressure of 40 mmHg, as the difference between resting flow and flow during maximal coronary vasodilation induced by intracoronary adenosine. Coronary vascular reserve, maximal coronary conductance, and coronary zero-flow pressure were not significantly altered by these anesthetics. The authors conclude that 1.0 MAC enflurane, halothane, and isoflurane mildly disrupt CBF autoregulation, increasing CBF out of proportion to myocardial demands. Under the conditions of this study, these anesthetics do not affect maximal CBF or coronary vascular reserve.     

Antagonism of general anesthesia by naloxone in the rat.

The effect of naloxone, a narcotic antagonist, on the response of animals to painful stimuli during anesthesia was studied. Rats were anesthetized with cyclopropane, halothane, or enflurane in groups of 12. Following induction, inspired anesthetic concentration was gradually reduced to a point at which 35-60 per cent of animals responded to tail clamping. Thereafter the anesthetic concentration was held constant for 30 minutes. Rats in each group then received saline solution or naloxone, 10mg/kg, given intravenously. The response to tail clamping was retested 5 minutes later. In additional experiments EEG's were recorded from rats anesthesized with one of these anesthetics. After a stable light plane of anesthesia had been attained, each animal was given naloxone, 10 mg/kg, iv, and the EEG recorded for an additional 5 minutes. In the tail-clamping experiments, naloxone approximately doubled the number of rats responding during cyclopropane, halothane, or enflurane anesthesia. The EEG patterns of several animals anesthetized with either cyclopropane or halothane changed to patterns consistent with lighter planes of anesthesia after naloxone administration. That naloxone alters the depth of inhalational anesthesia suggests that anesthetics may release an endogenous morphine-like factor (MLF) in the central nervous system.     

Combined depressant effects of diltiazem and volatile anesthetics on contractility in isolated ventricular myocardium

Because the volatile anesthetics depress the entry of calcium (Ca) into myocardial cells and also alter release of intracellular Ca stores, additional pharmacologic blockade of Ca entry could potentially enhance anesthetic-induced depression. The depressant effects of the calcium entry blocker diltiazem combined with the volatile anesthetics halothane, enflurane, or isoflurane were investigated in isolated guinea pig papillary muscle. Muscle contractions were studied in normal Tyrode solution after rest and at stimulation rates of 0.1, 0.25, 0.5, 1, 2, and 3 Hz. Anesthetics were studied in the presence of 0.1 and 1 microM diltiazem, which depressed tension to approximately 85 and 55% of control at 2-3 Hz, respectively; depression at the higher concentration was frequency-dependent. Depressant effects of enflurane were determined as previously done for equianesthetic concentrations (approximately 1 and 2 MAC) of halothane and isoflurane. At all stimulation rates, 1.7 and 3.5% enflurane depressed peak tension and dT/dt-max to approximately 73 and 50% of the mean control-recovery value, respectively. After control measurements of contractile characteristics, effects of 0.1 microM diltiazem were determined alone and then with the addition of halothane (0.75 or 1.5%), isoflurane (1.3 or 2.5%), or enflurane (1.7 or 3.5%), respectively. Recovery from anesthetic was then determined in the continued presence of diltiazem. After rest and at rates less than or equal to 0.5 Hz, equianesthetic concentrations of these volatile agents caused similar depression in the presence of diltiazem. At 3 Hz stimulation rate, 1.3% isoflurane caused significantly less contractile depression than did 1.7% enflurane or than 0.75% halothane. At 2-MAC concentrations, differences among the anesthetics were more apparent: 2.5% isoflurane depressed peak tension and dT/dt-max less than did halothane at 1-3 Hz stimulation rates, and depressed dT/dt-max less than 3.5% enflurane at 2-3 Hz. Similar frequency-dependent differences in depression by approximately 2 MAC anesthetics were observed in the presence of 1 microM diltiazem. The patterns of depressant action by the volatile anesthetics were similar to those previously observed in the absence of diltiazem. Furthermore, when the volatile anesthetic depression of contractions was combined with the depression due to diltiazem-induced blockade of Ca entry, the resulting contractile depression did not differ significantly from a prediction that assumed simply additive effects.     

Ca2+ uptake and Ca2+ release by skeletal muscle sarcoplasmic reticulum: differing sensitivity to inhalational anesthetics

The effects of halothane, enflurane, and isoflurane were measured on two different mechanisms of Ca2+ regulation by isolated skeletal muscle sarcoplasmic reticulum (SR) membranes. A 100,000-dalton Ca2+-ATPase protein transports Ca2+ from outside to inside the SR membrane. At concentration ranges representing anesthetic levels of 0.06 to 2.3 times MAC, halothane, enflurane, and isoflurane each increased rate of Ca2+ uptake by SR. Each concentration of isoflurane produced a greater rate of Ca2+ uptake, whereas halothane and enflurane produced maximum stimulation of Ca2+ uptake at 1 and 1.6 times MAC, respectively. The second Ca2+ regulation mechanism studied was a Ca2+ release channel in the SR membrane. The release of Ca2+ via this mechanism requires a critical threshold Ca2+ load (nmol Ca2+/mg SR protein) for Ca2+-induced Ca2+ release to occur. Each anesthetic tested effectively lowered the critical Ca2+ load threshold for Ca2+ release, i.e., the Ca2+ channel was more readily induced to an open state in the presence of anesthetic. The concentrations of anesthetics having this effect on the putative Ca2+ channel were between 0.0026 and 0.078 MAC equivalents for each agent, and these concentrations are much lower than the anesthetic concentrations affecting Ca2+ uptake. These data show that in isolated skeletal muscle SR membranes a Ca2+ channel release function is altered at anesthetic concentrations far below those that change Ca2+ uptake function by a Ca2+-ATPase and below concentrations of the volatile agents producing clinical anesthesia. The Ca2+ channel effect may represent protein-anesthetic interaction, whereas the Ca2+-ATPase effect may occur by a generalized SR membrane perturbation by the anesthetics.     

Prolongation of the QT interval by volatile anesthetics in chronically instrumented dogs

The influence of volatile anesthetics on ventricular repolarization in vivo (QT interval) has not been studied in a systematic fashion. The purpose of this investigation was to characterize the electrocardiographic and hemodynamic actions of the volatile anesthetics halothane, isoflurane, and enflurane in chronically instrumented dogs. Because autonomic nervous system tone may influence ECG findings, experiments were completed with and without concomitant pharmacologic autonomic nervous system blockade. In six groups comprising 50 experiments with 21 instrumented dogs, anesthesia was mask-induced with nitrous oxide, oxygen, and one of the volatile anesthetics and maintained with the volatile anesthetic in 100% oxygen for 2 hours. Changes in the ECG and in hemodynamics were compared to the conscious state. In the absence of autonomic nervous system blockade, halothane and isoflurane significantly prolonged the QT interval (0.24 +/- 0.01 to 0.30 +/- 0.01 second and 0.22 +/- 0.01 to 0.28 +/- 0.01 second, respectively), whereas enflurane produced no change in ventricular repolarization (0.24 +/- 0.01 to 0.26 +/- 0.01 second). All of the volatile anesthetics increased the QT interval corrected for changes in basal heart rate (QTc), and all agents decreased intravascular pressure and dP/dt. Following autonomic nervous system blockade, halothane, isoflurane, and enflurane significantly increased the QT interval and QTc. The results demonstrate that ventricular repolarization is directly altered by the volatile anesthetics independent of changes in autonomic nervous tone. Whether or not such effects are additive with other congenital or acquired forms of QTc prolongation has yet to be examined. The present results indicate that caution should be used during the administration of volatile anesthetics to patients with abnormalities of the QT interval.     

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.     

Mean equipotent blood pressure-lowering concentrations of halothane, isoflurane and enflurane during balanced anesthesia differ from conventional MAC-values]

Balanced anesthesia is a technique that allows control of blood pressure in patients with coronary artery disease. In order to evaluate the relative requirements of volatile anesthetics during basic opioid analgesia, 51 patients with unimpaired left ventricular function who were undergoing coronary artery bypass grafting during balanced anesthesia were investigated. They were randomly assigned to three groups, i.e. halothane (H), isoflurane (I), and enflurane (E). Permanent medications were maintained up to 12 h preoperatively. After premedication with flunitrazepam, promethazine and piritramide, anesthesia was induced with 7 micrograms/kg fentanyl, 0.3 mg/kg etomidate, and 0.1 mg/kg pancuronium and continued with fentanyl infusion (0.1 microgram/kg-1 min-1). Volatile anesthetics were applied in oxygen/air and adjusted to keep the mean arterial blood pressure within +/- 20% of the preoperative value. End-expiratory concentrations of volatile anesthetics were measured (Capnomac, DATEX) and averaged over time. The mean ages of the patients in the different groups were 60 +/- 7.6 years (H), 59 +/- 7.1 years (I), and 60 +/- 6.9 years (E). Four patients in the halothane group, six in the isoflurane group, and five in the enflurane group took beta-blockers preoperatively. The cumulative doses of fentanyl were: H = 0.80 +/- 0.17 mg, I = 0.85 +/- 0.16 mg, and E = 0.83 +/- 0.16 mg at the time of skin incision and H = 1.20 +/- 0.26 mg, I = 1.38 +/- 0.19 mg, and E = 1.24 +/- 0.25 mg at the beginning of extracorporeal circulation.2+ which are possibly the reason for the high O2-MAC value, which may be abolished during balanced anesthesia. However, both the negative inotropic and the vasodilatory effects of enflurane are more likely explanations for the results. It is concluded that 0.5 to 1.0 MAC of halothane, isoflurane, or enflurane used as equipotent components of balanced anesthesia for blood pressure control during aorto-coronary bypass grafting may differ considerably from the conventional MAC concept.     

The differential effects of halothane and isoflurane on windup of dorsal horn neurons selected in unanesthetized decerebrated rats

Halothane and isoflurane, in the peri-minimum alveolar anesthetic concentration (MAC) range, exert differential effects on spinal nociceptive neurons, whereby halothane further depresses their responses from 0.8 to 1.2 MAC, whereas isoflurane does not. We presently investigated if these anesthetics differentially affect windup, the progressive increase in neuronal responses to repetitive noxious stimuli, over a broad concentration range from 0 to 1.2 MAC. In decerebrated rats, single-unit recordings were made from dorsal horn neurons exhibiting windup to 20 1-Hz C-fiber strength electrical stimuli. Halothane and isoflurane (0, 0.4, 0.8, and 1.2 MAC) were tested in a counterbalanced crossover protocol. Increasing halothane and isoflurane from 0 to 1.2 MAC progressively suppressed the response to the first stimulus, as well as summed responses to all stimuli (to 34% +/- 8% and 50% +/- 8%, respectively; P < 0.05). Absolute windup (summed response minus 20x the first response) was suppressed by both anesthetics from 0 to 0.8 MAC, with further depression by halothane but not isoflurane at 1.2 MAC. Responses of neurons isolated at 0 MAC were partially, but never totally, depressed at 0.8 MAC. The dose-dependent suppression of windup is consistent with reduced temporal summation of pain. Further depression at 1.2 MAC halothane, but not isoflurane, suggests different sites of immobilizing action for these two anesthetics. Immobility seems to not be mediated by severe anesthetic depression of a subpopulation of nociceptive neurons.     

Minimum alveolar concentrations (MAC) of halothane, enflurane, and isoflurane in ferrets

The minimum alveolar concentrations (MAC) of isoflurane, enflurane, and halothane were determined in adult male ferrets during controlled ventilation at normothermia (37 degrees C). Mean (+/- SD) MAC values for isoflurane (n = 8), enflurane (n = 8), and halothane (n = 8) at 37 degrees C were 1.52 +/- 0.10%, 1.99 +/- 0.18%, and 1.01 +/- 0.10%, respectively. Halothane MAC was reduced by 26% in the presence of 70% N2O. At 29.9 +/- 0.2 degrees C, the mean MAC value of halothane (0.85 +/- 0.11%) was 16% less than MAC at 37 degrees C. The relative potencies of the halogenated anesthetics are of the same order as those reported for large animals and for humans.     

Effect of anesthetics and a convulsant on normal and mutant Caenorhabditis elegans

The authors have developed a method for studying the action of volatile anesthetics in Caenorhabditis elegans (C.e.), a free living nematode. C.e. appears to be a useful model for the study of the influence of genetics on susceptibility to anesthetics. This worm has a small, completely defined nervous system, easily manipulated genetics, and a large number of nervous system mutants. Under normal conditions C.e. moves almost constantly. When exposed to anesthetics there is an initial phase of increased locomotion, followed by uncoordinated motion that progresses to immobility. Motion returns quickly when the nematodes are removed from the anesthetic. The authors called loss of locomotion "anesthesia." The ED50S of various anesthetics with C.e. are as follows: methoxyflurane 0.45%, chloroform 1.25%, halothane 2.7%, enflurane 4.2%, isoflurane 5.6%, fluroxene 9.9%. The authors also studied the action of a convulsant, flurothyl, on C.e. Flurothyl has anesthetizing properties in these animals with an ED50 of 8.1%. No convulsant activity was noted. However, mixtures of halothane and flurothyl were antagonistic in their effects, while halothane and enflurane were additive. Furthermore, the authors isolated a mutant strain (HS1) of C.e. that shows altered responses to several anesthetics and a convulsant. HS1 is uncoordinated when not exposed to anesthetics. Like the normal strain (N2) HS1 loses mobility when exposed to anesthetics. The ED50S for various anesthetics in HS1 were as follows: methoxyflurane 0.04%, chloroform 0.52%, halothane 0.85%, isoflurane 4.9%, enflurane 6.0%, fluroxene 10.9%.(ABSTRACT TRUNCATED AT 250 WORDS)