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).     

Atracurium infusion requirements in children during halothane, isoflurane, and narcotic anesthesia

We were interested in determining the dose-response relationship of atracurium in children (2-10 yr) during nitrous oxide-isoflurane anesthesia (1%) and the atracurium infusion rate required to maintain about 95% neuromuscular blockade during nitrous oxide-halothane (0.8%), nitrous oxide-isoflurane (1%), or nitrous oxide-narcotic anesthesia. Neuromuscular blockade was monitored by recording the electromyographic activity of the adductor pollicis muscle resulting from supramaximal stimulation at the ulnar nerve at 2 Hz for 2 sec at 10-sec intervals. To estimate dose-response relationships, three groups of five children received 80, 100, 150 micrograms/kg atracurium, respectively. During isoflurane anesthesia, the neuromuscular block produced by 80 micrograms/kg was 23.6% +/- 6.5 (mean +/- SEM), by 100 micrograms/kg was 45% +/- 7.2, and by 150 micrograms/kg was 64% +/- 8.7. The ED50 and ED95 (estimated from linear regression plots of log dose vs probit of effect) were 120 micrograms/kg and 280 micrograms/kg, respectively. At equipotent concentrations, halothane and isoflurane augment atracurium neuromuscular block to the same extent, compared to narcotic anesthesia. Atracurium steady-state infusion requirements averaged 6.3 +/- 0.6 micrograms . kg-1 . min-1 during halothane or isoflurane anesthesia; the requirements during balanced anesthesia were 9.3 +/- 0.8 micrograms . kg-1 . min-1 (P less than 0.05). There was no evidence of cumulation during prolonged atracurium infusion.     

Pipecuronium-induced neuromuscular blockade during nitrous oxide-fentanyl, isoflurane, and halothane anesthesia in adults and children

To determine in adults and children the dose-response relationship and the duration of action of pipecuronium bromide during fentanyl-nitrous oxide (N2O), isoflurane, and halothane anesthesia, the authors studied 30 ASA Physical Status 1-2 adults (age: 16-55 yr) and 30 ASA Physical Status 1-2 children (age: 1.7-11.5 yr) during minor elective surgery. Patients were anesthetized with N2O/O2 (60:40) supplemented with either fentanyl (4 micrograms/kg), or isoflurane (adults, 0.9%; children, 1.2%), or halothane (adults, 0.6%; children, 0.7%). Neuromuscular (NM) blockade was measured by electromyography. Incremental iv doses of pipecuronium were administered to determine the cumulative dose-response relationship of pipecuronium until a 95% twitch depression (ED95) had been obtained. In adults, ED50 was 31.7 +/- 2.9 micrograms/kg (mean +/- SE) during fentanyl-N2O/O2, reduced by isoflurane (18.0 +/- 4.8 micrograms/kg, P less than 0.05) but not by halothane (25.0 +/- 2.6 micrograms/kg, NS). ED95 was 59.4 +/- 5.4 micrograms/kg during fentanyl-N2O/O2, reduced by isoflurane (42.3 +/- 2.5 micrograms/kg, P less than 0.05), but not by halothane (49.7 +/- 3.1 micrograms/kg, NS). In children, ED50 was 43.9 +/- 4.7 micrograms/kg during fentanyl-N2O/O2, reduced by isoflurane (23.1 +/- 1.6 micrograms/kg, P less than 0.05), and halothane (33.2 +/- 3.2 micrograms/kg, P less than 0.05). ED95 was 79.3 +/- 9.8 micrograms/kg during fentanyl-N2O/O2, and reduced by isoflurane (49.1 +/- 3.1 micrograms/kg, P less than 0.05), but not by halothane (62.5 +/- 7.3 micrograms/kg, NS). Comparison between adults and children reveals no statistically significant differences, except for ED50 during fentanyl-N2O/O2 anesthesia which was increased in children.(ABSTRACT TRUNCATED AT 250 WORDS)     

Neuromuscular and cardiovascular effects of mivacurium chloride (BW B109OU) during nitrous oxide-narcotic, nitrous oxide-halothane and nitrous oxide-isoflurane anesthesia in surgical patients

One hundred seventeen adult surgical patients were studied to compare neuromuscular and cardiovascular effects of mivacurium chloride during nitrous oxide-narcotic (BAL, n = 45) nitrous oxide-halothane (HAL, n = 27) and nitrous oxide-isoflurane (ISF, n = 45) anesthesia. Anesthesia was maintained with nitrous oxide (60%-70%) and oxygen (30%-40%) with end-tidal concentrations of halothane or isoflurane to yield a total MAC of approximately 1.25, or with supplemental fentanyl and thiopental as clinically indicated. Twitch response of the adductor pollicis muscle was elicited by supramaximal square wave pulses of 0.2 msec duration at a frequency of 0.15 Hz (Grass S44 stimulator) to the ulnar nerve and quantitated by a Grass FT10 transducer. Nine patients in each of the HAL and ISF groups received one of four doses of mivacurium (0.03, 0.05, 0.10 or 0.15 mg/kg). Ninety patients in the balanced anesthesia group received one of seven doses of mivacurium (0.03, 0.04, 0.05, 0.08, 0.15, 0.20, 0.25 mg/kg). The ED50, ED75 and ED95 of mivacurium in each group were estimated from linear regression plots of log dose versus probit of maximum percentage depression of twitch height. The ED50, ED75 and ED95 for halothane and isoflurane are 0.040, 0.053 and 0.081 and 0.037, 0.043 and 0.053, respectively. The ED50, ED75, and ED95 for the balanced group are 0.039, 0.050, and 0.073 mg/kg respectively. There was no significant difference between the slopes of the HAL and BAL inhalation anesthetic dose-response curves. The slope of the ISF group was significantly than the slope of the BAL group. Intercepts of the HAL and BAL curves were not different. The isoflurane curve's intercept was significantly less than the other groups' intercepts, lying above the halothane curve, but below the BAL curve. For the 0.05 mg/kg dose, maximum block was greater in the ISF group (89.1 +/- 2.7%, n = 9) than in the HAL (70.3 +/- 7.6%, n = 9) or BAL (67.7 +/- 6.4%, n = 9) groups. At higher doses of mivacurium, isoflurane produces a greater potentiation of neuromuscular block than halothane or balanced anesthesia. There were no significant cardiovascular changes seen in any group following mivacurium doses up to 0.15 mg/kg (approximately 2xED95).     

Pipecuronium-induced neuromuscular blockade during nitrous oxide-fentanyl, enflurane, isoflurane, and halothane anesthesia in surgical patients.

This study was designed to determine the capacity of several anesthetics to augment pipecuronium neuromuscular blockade. The potency of pipecuronium was determined with single-bolus administration of 20-50 micrograms/kg in 160 patients. Patients were anesthetized with N2O/O2 (60:40) supplemented with fentanyl (4-5 micrograms/kg), halothane (0.8%), isoflurane (1.2%), or enflurane (1.7%). Neuromuscular blockade was measured by an acceleration-responsive transducer (the Accelograph, Biometer International, Odense, Denmark). Responses were defined in terms of percent depression in first-twitch height and train-of-four response, and the dose-response curves were constructed after probit transformation of the responses. The dose-response curves were found to be parallel for both first twitch height and train-of-four responses. The dose-response lines for the enflurane and isoflurane groups were displaced significantly (P less than 0.01) to the left of the line for the fentanyl-N2O group. The calculated doses producing 50% depression of first twitch height were 21.9, 21.2, 18.9, and 17.8 micrograms/kg for the N2O-fentanyl, halothane, isoflurane, and enflurane groups, respectively. Corresponding calculated doses for 50% depression of train-of-four response were significantly smaller (15.5, 14.4, 13.7, 11.9 micrograms/kg, respectively). The enhancing effects of the volatile anesthetics were reflected by significant prolongation of the clinical duration of neuromuscular blockade by pipecuronium. It is concluded that the potency of pipecuronium is enhanced more by enflurane and isoflurane than halothane or fentanyl-N2O anesthesia.     

Dose-response relation and time course of action of pipecuronium bromide in humans anesthetized with nitrous oxide and isoflurane, halothane, or droperidol and fentanyl

The dose-response of pipecuronium bromide, the time course of its neuromuscular blocking effects, and the reversibility of the residual block by neostigmine and edrophonium have been investigated in patients undergoing various types of anesthesia. The estimated doses of pipecuronium required for 95% depression of the twitch height were 44.6, 46.9, and 48.7 micrograms.kg-1 during anesthesia with nitrous oxide (65%) and isoflurane (group 1), halothane (group 2), or droperidol/fentanyl (group 3), respectively. The potentiating effects of the volatile anesthetics were reflected by the significant prolongation of the duration of both initial (50.0 +/- 4.3, 36.0 +/- 3.3, and 29.0 +/- 2.0 minutes) and maintenance doses (56.0 +/- 2.5, 49.5 +/- 3.3, and 41.2 +/- 1.6 minutes) of pipecuronium during anesthesia with nitrous oxide and isoflurane, halothane, or droperidol/fentanyl, respectively. Both edrophonium chloride (0.5 mg.kg-1) and neostigmine methylsulphate (40 micrograms.kg-1) promptly reversed the residual block induced by pipecuronium. No side effects attributable to pipecuronium were seen in this study.     

Clinical pharmacology of mivacurium chloride (BW B1090U) in children during nitrous oxide-halothane and nitrous oxide-narcotic anesthesia

We determined the dose-response relationships of mivacurium (BW B1090U) in children (2-10 years) during nitrous oxide-halothane anesthesia (0.8% end-tidal) and during nitrous oxide-narcotic anesthesia. Neuromuscular blockade was monitored by recording the electromyographic activity of the adductor pollicis muscle resulting from supramaximal stimulation at the ulnar nerve at 2 Hz for 2 seconds at 10-second intervals. To estimate dose-response relationships, for each anesthetic background four subgroups of nine patients received single bolus doses of 20-120 micrograms/kg mivacurium. The ED50 and ED95 (estimated from linear regression plots of log-dose vs. probit of effect) were 52 micrograms/kg and 89 micrograms/kg during halothane anesthesia and 62 micrograms/kg and 103 micrograms/kg during narcotic anesthesia. Nine additional patients in each anesthetic group received 250 micrograms/kg mivacurium. Three of the 18 patients given 250 micrograms/kg mivacurium developed cutaneous flushing; in one of these mean arterial pressure decreased 32% for less than 1 minute; no significant changes in heart rate occurred. With the increase in mivacurium dose from 120 micrograms/kg to 250 micrograms/kg the times to onset of 90% and maximum neuromuscular block decreased by 0.5 to 1 minute, and the times to recovery of neuromuscular transmission to 5% (T5) or 25% (T25) increased by 2-4 minutes. The recovery index (T25-75) in patients anesthetized with halothane was 4.3 +/- 1.5 minute (mean +/- SD); the time to complete recovery (T4:1 greater than or equal to 0.75) was 19.8 +/- 7.4 minutes.     

Effects of enflurane, isoflurane, and nitrous oxide on somatosensory evoked potentials during fentanyl anesthesia

The effects of nitrous oxide, enflurane, and isoflurane on cortical somatosensory evoked potentials (SEPs) were studied in 29 patients undergoing intracranial or spinal operations. Anesthesia was induced with fentanyl (25 micrograms/kg, iv) plus thiopental (0.5-1.0 mg/kg, iv). In one group of patients (n = 12), nitrous oxide (50%) was compared with enflurane (0.25-1.0%), and in another group (n = 12) nitrous oxide (50%) was compared with isoflurane (0.25-1.0%). In a third group of patients (n = 5) with preexisting neurologic deficits, nitrous oxide (50%) was compared with enflurane (0.25-1.0%). In all three groups, one gas was administered for 30 min, and then the alternate gas was administered for 30 min; then the cycle was repeated for a total of two administrations of each of the two anesthetics. SEPs were determined before and after induction of anesthesia and at the end of each 30-min study period. The latencies and amplitudes of the early cortical components of the upper- and lower-extremity SEP were examined. Induction of anesthesia resulted in increases of latency in both upper- and lower-extremity SEPs without any alteration of amplitude. Nitrous oxide, enflurane, and isoflurane each decreased the amplitude of the upper-extremity SEPs compared with the postinduction value. The amplitude of the upper-extremity SEPs was less during nitrous oxide than with either enflurane or isoflurane. Nitrous oxide decreased the amplitude of lower-extremity SEPs below postinduction value, while enflurane and isoflurane had no effect. Isoflurane and enflurane increased the latency of both upper- and lower-extremity SEPs slightly, while nitrous oxide had no effect.(ABSTRACT TRUNCATED AT 250 WORDS)     

The dose-response relationship of mivacurium chloride in humans during nitrous oxide-fentanyl or nitrous oxide-enflurane anesthesia

The dose-response relationships of mivacurium chloride during N2O/fentanyl or N2O/enflurane anesthesia were compared in 70 patients intraoperatively. Responses were defined in terms of percentage changes in the evoked twitch tension of the adductor pollicis muscle, and dose-response curves were constructed following probit transformation of the responses. End-tidal concentrations of enflurane during the were study were 0.9-1.2%. When compared with the dose-response curve determined during N2O/fentanyl anesthesia the curve determined during N2O/enflurane anesthesia was displaced significantly to the left (P less than 0.05). As a result, the doses of mivacurium that depressed twitch tension by 50% (ED50) and 95% (ED95) were 39 and 67 micrograms/kg, respectively, during N2O/fentanyl anesthesia, and 27 and 52 micrograms/kg during N2O/enflurane anesthesia. Regression lines describing the relationship between the maximum depression of twitch tension (response) and the time interval between the injection of mivacurium and the return of twitch tension to 90% of the control value (duration) were constructed. The response-duration line for N2O/enflurane anesthesia was displaced significantly to the left of the line for N2O/fentanyl (P less than 0.05), indicating that enflurane anesthesia was associated with a prolongation of mivacurium-induced neuromuscular blockade. The neuromuscular blocking effect of mivacurium is both enhanced by and prolonged during N2O/enflurane compared with that during N2O/fentanyl anesthesia.     

Neuromuscular effects of atracurium during halothane-nitrous oxide and enflurane-nitrous oxide anesthesia in humans

To compare the effect of halothane and enflurane on an atracurium-induced neuromuscular blockade, the authors studied 40 patients during elective surgery. During 1.25 MAC enflurane-nitrous oxide (n = 20) or halothane-nitrous oxide (n = 20) (MAC value includes contribution from 60% nitrous oxide), the doses depressing twitch tension 50% (ED50S) for atracurium were 70 and 77 micrograms/kg, respectively. The difference was not significant. Time from injection to peak effect did not differ between groups. However, the duration of action of atracurium (expressed as duration 50 or the duration of a 50% blockade) was longer during enflurane-nitrous oxide anesthesia (34.2 min) than during halothane-nitrous oxide anesthesia (25.5 min) (P less than 0.05). The authors conclude that the potency of atracurium does not differ during halothane-nitrous oxide and enflurane-nitrous oxide anesthesia. Combining the results of this study with a previous study (atracurium ED50 = 68 micrograms/kg and 83 micrograms/kg during isoflurane-nitrous oxide and fentanyl-nitrous oxide anesthesia respectively), the potency of atracurium does not differ by more than 20% among the four anesthetic techniques studied. The background anesthetic appears to have less effect on an atracurium-induced neuromuscular blockade than on one produced by other longer-acting nondepolarizing muscle relaxants (e.g., pancuronium and d-tubocurarine).     

Clinical pharmacology of doxacurium chloride. A new long-acting nondepolarizing muscle relaxant

Doxacurium chloride (BW A938U) is a bis-quaternary benzylisoquinolinium diester nondepolarizing neuromuscular blocking compound that is minimally hydrolyzed by human plasma cholinesterase. The effect of bolus doses of doxacurium ranging from 10 to 80 micrograms/kg were studied in 81 consenting ASA physical status I and II patients anesthetized with nitrous oxide-oxygen-fentanyl-thiopental. The neuromuscular and cardiovascular effects of doxacurium were compared with those of eight patients receiving 100 micrograms/kg of pancuronium receiving identical anesthesia. The calculated ED95 for evoked twitch inhibition of the adductor pollicis at 0.15 Hz was 30 micrograms/kg. At 1.3 times the ED95 dose of doxacurium, recovery times to 5% and 25% of control twitch height were 59.2 +/- 4.1 (n = 23 of 26) and 75.7 +/- 5.6 (n = 23 of 26) min respectively. For pancuronium comparable recovery times were 81.7 +/- 10.3 (n = 8 of 8) and 83.0 +/- 8.4 (n = 5 of 8) min. Residual doxacurium blockade was readily antagonized by neostigmine. No dose-related effect on heart rate or mean arterial pressure was seen with doxacurium at doses up to and including 2.7 times the ED95 (80 micrograms/kg). Doxacurium administration did not result in any elevation of plasma histamine at doses up to and including 2.7 times the ED95. In this study doxacurium appears to be a long-acting nondepolarizing relaxant with readily reversible neuromuscular blocking effects and devoid of cardiovascular effects. This profile offers clinical advantages over current long-acting agents and further clinical trials seem appropriate.     

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.     

The Effect of Isoflurane, Halothane, Sevoflurane, and Thiopental/Nitrous Oxide on Respiratory System Resistance after Tracheal Intubation

Background: After tracheal intubation, lung resistance and therefore respiratory system resistance (Rrs) routinely increase, sometimes to the point of clinical bronchospasm. Volatile anesthetics generally have been considered to be effective bronchodilators, although there are few human data comparing the efficacy of available agents. This study compared the bronchodilating efficacy of four anesthetic maintenance regimens: 1.1 minimum alveolar concentration (MAC) end-tidal sevoflurane, isoflurane or halothane, and thiopental/nitrous oxide.

Methods: Sixty-six patients underwent tracheal intubation after administration of 2 micro gram/kg fentanyl, 5 mg/kg thiopental, and 1 mg/kg succinylcholine. Vecuronium or pancuronium (0.1 mg/kg) was then given to ensure paralysis during the rest of the study. Postintubation R sub rs was measured using the isovolume technique. Maintenance anesthesia was then randomized to thiopental 0.25 mg [center dot] kg sup -1 [center dot] min sup -1 plus 50% nitrous oxide, or 1.1 MAC end-tidal isoflurane, halothane, or sevoflurane. The Rrs was measured after 5 and 10 min of maintenance anesthesia. Data were expressed as means +/- SD.

Results: Maintenance with thiopental/nitrous oxide failed to decrease Rrs, whereas all three volatile anesthetics significantly decreased Rrs at 5 min with little further improvement at 10 min. Sevoflurane decreased Rrs more than either halothane or isoflurane (P < 0.05; 58 +/- 14% of the postintubation Rrs vs. 69 +/- 20% and 75 +/- 13%, respectively).     

Narcotics decrease heart rate during inhalational anesthesia

We determined the heart rate (HR) response to enflurane, halothane, and isoflurane and the effects of narcotics on this response in 81 healthy patients scheduled for elective surgery. Patients were randomly assigned to one of six treatment groups: one of the three anesthetics (approximately 0.9 MAC) in 60% nitrous oxide, and either 0.15 mg/kg of intramuscular morphine 30-60 min before induction or 1 microgram/kg of IV fentanyl 10 min after skin incision. All patients received diazepam, 10 mg orally, 60-90 min before anesthesia, a rapid sequence intravenous induction, and mechanically controlled ventilation. During inhalational anesthesia and the first 10 min of surgery, no significant change in HR occurred in any group (compared to the preinduction HR), although patients given morphine premedication tended to have a decreased HR and those not given morphine premedication tended to have an increased HR. These trends partially account for significant differences that emerged between groups after induction of anesthesia. Patients given morphine premedication and halothane had lower HR (64 +/- 3 SEM) than patients given isoflurane (80 +/- 3) or enflurane (84 +/- 3) and no morphine premedication. Patients anesthetized with enflurane and morphine premedication had lower HR (71 +/- 3) than patients given enflurane without morphine premedication. Administration of fentanyl 10 min after incision (these patients had received no morphine) significantly decreased HR in the presence of any of the vapors. We conclude that inhalational anesthetics used in the clinical setting we employed do not significantly increase heart rate, and that prior administration of morphine or concurrent administration of fentanyl may significantly decrease HR.     

Effects of halothane and fentanyl on the rate of CSF production in dogs

Using the open ventriculocisternal perfusion method, the rate of cerebrospinal fluid (CSF) production was examined in dogs anesthetized with either halothane (0.8%) or fentanyl (3.0 micrograms/kg/min for 20 min, then 0.2 micrograms/kg/min, intravenously), and nitrous oxide (60-70%) in oxygen. Halothane decreased the mean rate of CSF production from 0.047 +/- 0.006 ml/min (mean +/- SEM) in controls to 0.033 +/- 0.005 ml/min. This effect persisted throughout 3.0-3.5 h of anesthesia. When the expired concentration of halothane was decreased from 0.8% to less than 0.1%, the mean rate of CSF production returned to control values within 45-50 min. Fentanyl produced no change in the mean rate of CSF production compared to controls. These data suggest that increased CSF volume does not contribute to increased intracranial pressure during prolonged halothane anesthesia. In patients at risk for increased intracranial pressure due to increased CSF volume, either halothane or fentanyl may be preferable to anesthetics that may increase CSF production, e.g., enflurane.     

POTENTIATION OF THE NEUROMUSCULAR BLOCKADE PRODUCED BY ALCURONIUM WITH HALOTHANE, ENFLURANE AND ISOFLURANE

The potentiation of alcuronium by halothane, enflurane and isofluranewas investigated using electromyography. In the first study,cumulative dose-response curves were constructed in four groupsof 10 patients anaesthetized with one of the inhalation agentsand nitrous oxide, or with fentanyl and droperidol (control).All three agents reduced the ED₅₀ of alcuronium; the effectwas marked with isoflurane (P < 0.005) but less so with halothane(P < 0.05) and enflurane (ns). In the second part of theinvestigation, designed primarily to test the duration of actionof alcuronium with each agent, a single bolus dose of alcuronium0.2 mg kg^–1 was given to four similar groups (n = 5).The duration of action was significantly prolonged by enflurane(P < 0.01) and isoflurane (P < 0.05), but not by halothane.The possible reasons for this are discussed.     

Effect of fentanyl and nitrous oxide on the desflurane anesthetic requirement

The minimum alveolar anesthetic concentration (MAC) of desflurane (I-653) was determined when administered with 60% nitrous oxide (N2O) in oxygen after a standardized induction sequence consisting of 0, 3, 6, or 9 micrograms/kg intravenous (IV) fentanyl followed by 3-6 mg/kg IV thiopental and 1.5 mg/kg IV succinylcholine. For comparison, we also determined the isoflurane MAC with 60% N2O in oxygen after an induction dose of 3 micrograms/kg IV fentanyl and similar doses of thiopental and succinylcholine. All patients were undergoing elective surgical procedures. The minimum alveolar anesthetic concentration in patients given isoflurane and 60% N2O with 3 micrograms/kg fentanyl was 0.4%, approximately 20% below previously reported MAC values for isoflurane with 60% N2O alone. The minimum alveolar anesthetic concentration of desflurane with 60% N2O plus 0, 3, 6, and 9 micrograms/kg IV fentanyl was 3.7%, 3.0%, 1.2%, and 0.1%, respectively. Thus, the MAC-lowering effect of 3 micrograms/kg IV fentanyl appears to be similar with both isoflurane and desflurane. Fentanyl, 3-9 micrograms/kg IV, produces dose-dependent decreases in the MAC of desflurane.     

Does choice of anesthetic agent significantly affect outcome after coronary artery surgery?

A prospective study of 1094 consecutive adult patients undergoing coronary revascularization was undertaken to determine the effect of anesthetic technique on outcome. Patients received one of five primary techniques: high-dose fentanyl (greater than 50 micrograms/kg), moderate-dose fentanyl (less than 50 micrograms/kg), sufentanil (3-8 micrograms/kg), diazepam (0.4-1 mg/kg) with ketamine (3-6 mg/kg) or halothane (0.5-2.5% inspired concentration after thiopental induction). Supplemental inhalation anesthesia (enflurane, halothane, or isoflurane) was used in 60% of cases where the primary technique was intravenous based. Patients in the above anesthetic groupings had similar perioperative demographic and risk classifications. The overall incidence of postoperative myocardial infarction, postoperative low cardiac output state, and in-hospital death were 4.1, 5.6, and 3.1%, respectively. There were no significant differences in the incidence of these occurrences or in the incidence of serious pulmonary, renal, or neurologic morbidity or length of ICU stay among primary anesthetic techniques nor among supplemental inhalation agent groups. Multivariate discriminant analysis of this data suggests that a multitude of factors are significantly more important than anesthetic technique as determinants of outcome after coronary artery surgery.     

Cerebral blood flow and metabolism in patients undergoing anesthesia for carotid endarterectomy. A comparison of isoflurane, halothane, and fentanyl

The effects of isoflurane, halothane, and fentanyl on cerebral blood flow (CBF) and cerebral metabolic rate for oxygen (CMRO2) during anesthesia prior to carotid endarterectomy were compared using the intravenous method of 133-Xenon CBF determination. Patients, mean (+/- SE) age 68 +/- 2, received either isoflurane (N = 16), 0.75% in O2 and N2O, 50:50; halothane (N = 11), 0.5% in O2 and N2O, 50:50; or fentanyl (N = 10), 5-6 micrograms/kg bolus and then 1-2 micrograms.kg-1.h-1 infusion in addition to O2 and N2O, 40:60. Measurements were made immediately before carotid occlusion. Mean (+/- SE) CBF (ml.100 g-1.min-1) was 23.9 +/- 2.1 for isoflurane, 33.8 +/- 4.8 for halothane, and 19.3 +/- 2.4 for fentanyl. CMRO2 (ml.100 g-1.min-1) was available from 22 patients and was 1.51 +/- 0.28 for isoflurane (N = 7), 1.45 +/- 0.24 for halothane (N = 6), and 1.49 +/- 0.21 for fentanyl (N = 9). Although CBF was greater during halothane than during isoflurane or fentanyl anesthesia (p less than 0.05), there were no demonstrable differences in CMRO2 among the 3 agents. We conclude that choice of anesthetic agent for cerebrovascular surgery with comparable anesthetic regimens should not be made on the basis of "metabolic suppression." During relatively light levels of anesthesia, vasoactive properties of anesthetics are more important than cerebral metabolic depression with respect to effects on the cerebral circulation.     

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.