Anesthetic interactions of midazolam and fentanyl: is there acute tolerance to the opioid?

The anesthetic effects and interactions of midazolam and fentanyl were determined in terms of their reduction of enflurane MAC in dogs, and the effects of their specific antagonists were also investigated. Control enflurane MAC was determined by the tail clamp method in 18 mongrel dogs. Each animal then received an iv loading dose of midazolam followed by a constant infusion at 9.6 micrograms.kg-1.min-1 designed to produce a stable enflurane MAC reduction of approximately 40%, and enflurane MAC was determined following a 60-min observation period during which time the midazolam concentration in plasma stabilized. Fentanyl was then administered in a series of three incremental loading doses (15, 30, and 225 micrograms/kg) and infusions (0.05, 0.2, and 3.2 micrograms.kg-1.min-1) designed to produce enflurane MAC reductions of 30%, 50%, and 65%, respectively. Enflurane MAC was again determined following a 60-min observation period for each new infusion. In nine dogs after the fourth determination of enflurane MAC, fentanyl was discontinued and 1 mg/kg naloxone was administered iv every 10 min until enflurane MAC was determined for the last time. In the other nine dogs, midazolam was discontinued and 1.5 mg/kg flumazenil (RO 15-1788) was administered and enflurane MAC determined for the last time. The midazolam concentration in plasma remained stable at 414 +/- 134 ng/ml throughout the study, and in the absence of fentanyl reduced enflurane MAC by 40 +/- 10% (mean +/- SD). The addition of fentanyl produced significant further reductions in enflurane MAC.(ABSTRACT TRUNCATED AT 250 WORDS)     

Less than additive antinociceptive interaction between midazolam and fentanyl in enflurane-anesthetized dogs

The anesthetic interactions of midazolam and fentanyl were determined in terms of enflurane MAC reduction in dogs. In part 1, 8 animals received an intravenous (iv) loading dose of fentanyl followed by a constant infusion at 0.05 micrograms.kg-1.min-1 to produce a stable enflurane MAC reduction of approximately 20%. Midazolam was then administered in a series of three incremental loading doses and infusions (2.4, 9.6, and 28.8 micrograms.kg-1.min-1 previously determined to produce enflurane MAC reductions of approximately 30, 45, and 60%, respectively. Enflurane MAC was determined for each infusion. Then fentanyl was discontinued; naloxone 1 mg/kg was administered; and enflurane MAC was determined. In part 2, six dogs received a loading dose and a continuous infusion of fentanyl (0.2 micrograms.kg-1.min-1) designed to produce a stable enflurane MAC reduction of approximately 40%. A series of two incremental loading doses and infusions of midazolam (2.4 and 28.8 micrograms.kg-1.min-1) were added, and MAC determinations were repeated at each infusion rate. Then midazolam was discontinued; flumazenil (RO 15-1788) 1.5 mg/kg was administered; and enflurane MAC was determined. The fentanyl concentrations in plasma remained stable at 1.0 +/- 0.3 ng/ml (mean +/- standard deviation [SD], part 1) and 3.1 +/- 0.5 ng/ml (part 2) throughout the study and, in the absence of midazolam, reduced enflurane MAC by 28 +/- 11 and 44 +/- 5%, respectively. The addition of midazolam produced significant further reductions in enflurane MAC, but the reductions were less than those predicted on the basis of an additive interaction. Naloxone returned enflurane MAC reduction to that expected for midazolam alone (part 1).(ABSTRACT TRUNCATED AT 250 WORDS)     

Thiopental and epinephrine-induced dysrhythmias in dogs anesthetized with enflurane or isoflurane

Epinephrine-induced dysrhythmias were studied in 19 dogs anesthetized with 1.25 MAC enflurane or isoflurane, or the same preceded by thiopental (20 mg/kg). In 11 (group 1) dogs, thiopental reduced the dose of epinephrine required for production of ventricular ectopy, bigeminy and tachycardia with enflurane, and only ventricular tachycardia with isoflurane (P less than 0.05). Thiopental potentiation of epinephrine-induced dysrhythmias with enflurane lasted 4 hr after induction. In eight (group 2) dogs, the arrhythmic dose (ADE in microgram/ml) and plasma level of epinephrine (PLE in ng/ml) for four or more ventricular extrasystoles in 15 sec were determined in the same animal under each of the four test conditions. ADE and PLE values (X +/- SEM) were, respectively, enflurane, 9.1 +/- 1.0 and 141 +/- 24 (8/8 dogs); enflurane-thiopental, 5.0 +/- 0.6 and 63 +/- 16 (8/8 dogs); isoflurane, 28.3 and 330 (1/7 dogs); and isoflurane-thiopental, 15.2 +/- 2.8 and 265 +/- 59 (5/7 dogs). In addition, thiopental had no effect on plasma epinephrine levels reached during epinephrine infusions with 1.0 (enflurane only), 2.0 (enflurane, isoflurane) and 4.0 micrograms X kg-1 X min-1 (isoflurane only). Nor were epinephrine levels reached during enflurane or enflurane-thiopental different from those reached during isoflurane or isoflurane-thiopental. It is concluded that thiopental potentiates several types of epinephrine-induced ventricular dysrhythmias with enflurane, but only ventricular tachycardia with isoflurane. Furthermore, isoflurane or isoflurane-thiopental were less sensitizing than enflurane or enflurane-thiopental. Finally, neither thiopental nor the anesthetic agents affected plasma epinephrine levels reached during epinephrine infusions lasting 3 min.     

Effect of halothane,enflurane and isoflurane on the end-systolic pressure-length relationship

Myocardial contractility was measured using the end-systolic pressure-length (ESPL) relationship in dogs subjected to increasing concentrations of halothane (0.5-2 per cent), enflurane (0.77-2.6 per cent) or isoflurane (0.70-2.13 per cent), combined with an infusion 7 micrograms X kg-1 X min-1 of fentanyl, after induction of anaesthesia with 15 mg X kg-1 thiopentone. The relationship between the concentrations of the different drugs and contractility (ESPL) can best be described by ESPL = a + b/(MAC fraction) where "a" is a constant and "b" is the slope of the curve relating ESPL to MAC. At 1.0 MAC values, the ESPL for halothane (69.04 +/- 25.83 mmHg X mm-1) did not differ from that of isoflurane (63.19 +/- 17.36 mmHg X mm-1). However, the myocardial contractility during 1.0 MAC halothane and isoflurane anaesthesia was better preserved than that of enflurane (38.66 +/- 9.73 mmHg X mm-1: p less than 0.01, p less than 0.05 respectively).     

Flumazenil improves cognitive and neuromotor emergence and attenuates shivering after halothane-, enflurane- and isoflurane-based anesthesia

PURPOSE: To conduct a randomized, placebo-controlled, double-blinded, clinical experiment testing the hypothesis that flumazenil, a benzodiazepine antagonist, may affect recovery from halothane-, enflurane- and isoflurane-based anesthesia. METHOD: Patients who underwent surgery under N(2)O/O(2) plus halothane (n=100), enflurane (n=100) or isoflurane (n=70) anesthesia were administered flumazenil 1 mg or placebo upon emergence from anesthesia, and their postanesthesia vital signs, vigilance, neurological recovery, shivering, amnesia reversal, and general subjective feeling were assessed. RESULTS: A ten-point vigilance score showed better recovery of flumazenil-treated patients compared to those who received placebo (60-min after halothane anesthesia: 9.9 +/- 0.1 vs 9.5 +/- 0.2, P <0.01; after enflurane: 10 +/- 0 vs 9.4 +/- 0.2, P <0.01; after isoflurane: 10.0 +/- 0 vs 9.3 +/- 0.1, P <0.01). Halothane- and enflurane-flumazenil-treated patients (but not isoflurane) reached a better neurological score (2.97 +/- 0.05 or 3 +/- 0) compared to placebo (2.8 +/- 0.4 or 2.6 +/- 0.4, P <0.01), respectively. Reversal of amnesia was superior in the flumazenil group at 60 min and at 24 hr postsurgery, and more flumazenil patients rated recovery as "pleasant". Flumazenil patients shivered less than placebo patients despite their lower core temperature (at 30 min: halothane: 11% vs 28%, P <0.05; enflurane: 11% vs 30%, P <0.05; isoflurane: 17% for both groups). CONCLUSION: Flumazenil improves recovery of high cortical and neuromotor functions following halothane, enflurane and isoflurane anesthesia, reduces shivering and improves the overall quality of emergence, including patients' subjective feeling.     

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 enflurane sparing effect of sufentanil in dogs

There is a ceiling to the reduction of enflurane MAC by fentanyl in the dog. Sufentanil (SUF), a more potent narcotic, may be more efficacious in reducing enflurane MAC. To test this hypothesis, 25 mongrel dogs were studied in three groups. Group 1 (n = 8) received SUF in progressively increasing infusion rates from 0.005 micrograms . kg-1 . min-1 to a maximum of 1.215 micrograms . kg-1 . min-1. MAC was determined at stable SUF concentrations in plasma [SUF] during each infusion rate. Group 2 (n = 10) received SUF at a dose rate (0.007 micrograms . kg-1 . min-1) designed to produce approximately 35% MAC reduction, and MAC determinations were made at regular intervals over a mean infusion time of 7.6 +/- 0.43 h (mean +/- SEM). Group 3 (n = 7) received 1.215 micrograms . kg-1 . min-1 and were studied as in group 2 over an infusion time of 6.7 +/- 0.42 h. In group 1, the highest infusion rate (1.215 micrograms . kg-1 . min-1) produced [SUF] = 48 ng/ml and reduced MAC by 71 +/- 6%. This was not statistically different from the reduction which occurred at [SUF] = 0.92 ng/ml (57 +/- 7%; infusion rate 0.015 micrograms . kg-1 . min-1; P = 0.21). In group 2, the degree of MAC reduction achieved by stable [SUF] (0.54 +/- 0.08 ng/ml) declined over time (MAC reduction at start = 34 +/- 2% versus 18 +/- 4.0% at the end of the infusion; P = 0.001), suggesting the development of tolerance.(ABSTRACT TRUNCATED AT 250 WORDS)     

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).     

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.     

Halothane, isoflurane, and enflurane MAC in pregnant and nonpregnant female and male mice and rats

The MAC of halothane, isoflurane, and enflurane was determined using the tail-clamp technique in pregnant female, nonpregnant female, and male Swiss Webster mice (n = 216) and Sprague-Dawley rats (n = 112). Mean MAC values (+/-SD) for halothane, isoflurane, and enflurane in mice were 0.95 +/- 0.07%, 1.34 +/- 0.10%, and 1.95 +/- 0.16%, respectively; values in rats were 1.03 +/- 0.04%, 1.46 +/- 0.06%, and 2.21 +/- 0.08%, respectively, all significantly higher than in mice. Neither the sex of the animals nor whether female animals were pregnant influenced the results.     

MAC for halothane, enflurane, and isoflurane in the New Zealand white rabbit: and a test for the validity of MAC determinations

MAC determinations for halothane, enflurane, and isoflurane were performed in New Zealand white rabbits (n = 8, approximate age 6 months). The MAC values (+/-SD) were as follows: halothane 1.39 +/- 0.23%, enflurane 2.86 +/- 0.18%, and isoflurane 2.05 +/- 0.18%. Comparison of these results with published MAC values for other species suggests that the ratio of the potencies for any pairing of these three agents is constant from species to species. This observation provides a means for assessing the validity of preexisting or newly determined MAC values.     

Intrabiliary pressure changes produced by inhalational anesthetics in dogs]

The common bile duct pressure was studied in dogs under inhalation of 1.0 MAC and 2.0 MAC of halothane, enflurane, isoflurane or sevoflurane. A double lumen catheter was inserted into the common bile duct through the cholecystic duct for the measurement of intraductal pressure in the choledochoduodenal junction. The intra-bile-ductal pressure (IBP) was measured with constant rate infusion methods every 10 minutes for one hour. After obtaining control IBP measurements, 44 dogs received randomly either 1.0 MAC (n = 6 in each group) or 2.0 MAC (n = 5 in each group) of each four inhalational anesthetics, through a non-rebreathing system. The decreases in IBP produced by 1.0 MAC concentrations of four inhalation anesthetics were not statistically significant although there was a decline from control measurements obtained for each group. The elevations of IBP following 2.0 MAC halothane, isoflurane or sevoflurane were significantly depressed and were 38.3 +/- 21.2, 67.5 +/- 23.8, 63.7 +/- 23.7 (%, mean +/- SD) of the control levels, respectively. However, 2.0 MAC enflurane produced no significant decrease in IBP.     

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.     

Dose-response relationships of doxacurium chloride in humans during anesthesia with nitrous oxide and fentanyl, enflurane, isoflurane, or halothane

In a two-part study, the dose-response relationships of doxacurium chloride (BW A938U) were evaluated during general anesthesia maintained with commonly used anesthetic techniques. In part 1, cumulative dose-response methodology was used to establish the ED95 of doxacurium in 36 patients receiving 70% nitrous oxide and fentanyl, or 50% nitrous oxide and either 1.26% enflurane, 0.84% isoflurane, or 0.57% halothane anesthesia. Mechanomyographic response to train-of-four stimulation was used to monitor neuromuscular blockade. The peak effect of doxacurium following each 5 micrograms/kg incremental dose was noted and a log-probit dose-response curve was constructed for each individual patient. The median ED50s were 11 micrograms/kg, 6 micrograms/kg, 8 micrograms/kg, and 8 micrograms/kg for patients receiving fentanyl, enflurane, isoflurane, or halothane anesthesia, respectively. The median ED95s were 24 micrograms/kg, 14 micrograms/kg, 16 micrograms/kg, and 19 micrograms/kg for patients receiving fentanyl, enflurane, isoflurane, and halothane anesthesia, respectively. In part 2, 72 additional patients received a rapid single injection of the ED95 (n = 36) or 2 X ED95 (n = 36) of doxacurium appropriate for the administered anesthetic as estimated from part one of the study. Peak effects of the ED95 given as single injections correlated well with the results in part 1.(ABSTRACT TRUNCATED AT 250 WORDS)     

Reduction of the MAC of desflurane with fentanyl.

Opioids are known to affect the MAC of inhalational anesthetics. We have determined the interaction between fentanyl and desflurane, following a bolus injection of fentanyl at induction in 134 adult patients. Five groups of patients were studied. Four groups received desflurane or isoflurane in oxygen with either fentanyl 3 or 6 micrograms/kg and thiopental 2-5 mg/kg given as a bolus injection at the time of induction. An additional group received desflurane in oxygen alone. Groups were stratified by age. MAC determination, in response to the stimulus of skin incision, was made using the "up-down" method and logistic regression. The MAC desflurane in oxygen was 6.3% (5.3-7.6%, 95% confidence interval [CI]). Fentanyl 3 micrograms/kg produced a fentanyl plasma concentration of 0.78 +/- 0.53 ng/ml at skin incision and resulted in a MAC for desflurane of 2.6% (2.0-3.2%, 95% CI) %. Fentanyl 6 micrograms/kg produced a fentanyl plasma concentration of 1.72 +/- 0.76 ng/ml at skin incision and resulted in a MAC for desflurane of 2.1% (1.5-2.6%, 95% CI). To compare recovery times to eye-opening and response to commands, patients were grouped according to the plasma fentanyl concentrations at the time of awaking. Recovery was faster in patients who received desflurane than in those who received isoflurane. The authors conclude that the MAC of desflurane is significantly reduced 25 min following a single dose of 3 micrograms/kg of fentanyl and that increasing the fentanyl dose to 6 micrograms/kg produces little further decrease in MAC. Desflurane is also associated with faster recovery from anesthesia than is isoflurane.     

Fentanyl Augments the Blockade of the Sympathetic Response to Incision (MAC-BAR) Produced by Desflurane and Isoflurane: Desflurane and Isoflurane MAC-BAR without and with Fentanyl

Background: Heart rate (HR) or mean arterial blood pressure (MAP) may increase in response to incision despite the absence of a motor response. The authors hypothesized that the MAC-BAR (minimum alveolar concentration of an anesthetic that blocks adrenergic response to incision) for isoflurane would exceed that for desflurane, and that fentanyl would decrease the MAC-BAR for each anesthetic in a dose-dependent manner.

Methods: Seventy-one patients were randomly allocated to one of six groups: desflurane or isoflurane without fentanyl or with 1.5 or 3 micro gram/kg fentanyl given intravenously 5 min before surgical incision. Anesthesia was induced with 2 mg/kg propofol given intravenously, and tracheal intubation facilitated with 0.1 mg/kg given intravenously. The first patient in each group received 1 MAC (end-tidal) of the inhaled anesthetic in 60% nitrous oxide (0.55 MAC), balance oxygen, maintained for at least 10 min before incision. The response was considered positive if the HR or MAP increased 15% or more. If the response was positive, the end-tidal concentration given to the next patient was 0.3 MAC greater; if the response was negative, the end-tidal concentration was 0.3 MAC less. The MAC-BAR level was calculated as the mean of four independent cross-over responses in each group.

Results: Desflurane and isoflurane anesthesia with 60% nitrous oxide did not change HR (P > 0.05) and decreased MAP (P < 0.05) before incision. Plasma epinephrine and norepinephrine concentrations after anesthesia and before incision were normal in all groups. The MAC-BAR level, without fentanyl, did not differ (P > 0.05) between desflurane (1.30 +/- 0.34 MAC [mean +/- SD]) and isoflurane (1.30 +/- 0.18 MAC). Fentanyl given at 1.5 micro gram/kg intravenously equivalently (P > 0.05) reduced the MAC-BAR for desflurane (to 0.40 +/- 0.18 MAC; P <0.05) and isoflurane (to 0.55 +/- 0.00 MAC; P < 0.05), but a further increase in fentanyl to 3 micro gram/kg caused no greater decrease in the MAC-BAR for desflurane (0.48 +/- 0.16 MAC) and isoflurane (0.40 +/- 0.30 MAC).     

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.     

L-644,711, a novel anion transport inhibitor, increases isoflurane MAC in rats.

The effect of the anion transport inhibitor L-644,711 on isoflurane MAC was determined in rats (n = 24). After baseline MAC determination, each rat received one of the following drug protocols: (a) control, vehicle only; (b) L-644,711IT, a 3-mg/kg intrathecal bolus of L-644,711 followed by an infusion at 1.5 mg.kg-1.h-1; or (c) L-644,711IV, a 6-mg/kg intravenous bolus of L-644,711 followed by an infusion at 3 mg.kg-1.h-1. MAC was again determined. The baseline isoflurane MAC was not different between groups (control, 1.52% +/- 0.15%; L-644,711IT, 1.51% +/- 0.24%; L-644,711IV, 1.54% +/- 0.13% [mean +/- SD]). After drug or vehicle administration, isoflurane MAC was larger for the L-644,711IT group (2.25% +/- 0.17%) versus the control (1.38% +/- 0.13%) and L-644,711IV (1.39% +/- 0.15%) groups (P less than 0.05). These data are consistent with the hypothesis that isoflurane anesthesia is influenced by anion channels and that blocking these channels may reduce the pharmacodynamic potency of isoflurane.     

Comparative effects of halothane, enflurane, and isoflurane at equipotent anesthetic concentrations on isolated ventricular myocardium of the ferret. I. Contractility

The effects of halothane, enflurane, and isoflurane on myocardial contractility were compared in papillary muscles of the right ventricle of adult male ferrets at 30 degrees C. Isotonic and isometric variables of contractility were measured before, during, and after exposure to incremental concentrations of halothane (n = 9 muscles), enflurane (n = 9 muscles), and isoflurane (n = 9 muscles), in steps of 0.25 MAC up to 1.5 MAC of halothane and of enflurane, and up to 2.0 MAC of isoflurane. Each of the three anesthetics caused a dose-dependent reversible decrease in contractility. The onset of maximal myofibrillar activation was delayed in a dose-dependent manner, and time to peak shortening of the isotonic preloaded twitch was unchanged, except for a slight decrease at greater than 1 MAC of enflurane. Isoflurane's negative inotropic effects were clearly less than those of either halothane or enflurane. Comparison of the time course of contraction and relaxation in both isometric and isotonic twitches suggests that, in addition to effects on intracellular calcium availability, these anesthetics decrease the myofibrillar responsiveness to calcium and/or the calcium sensitivity of the contractile proteins.     

Which drug prevents tachycardia and hypertension associated with tracheal intubation: lidocaine, fentanyl, or esmolol?

Eighty patients, ASA physical status II-IV, scheduled for noncardiac surgery, were randomly assigned in a double-blind, placebo-controlled manner to receive a preintubation dose of either placebo, 200 mg lidocaine, 200 micrograms fentanyl, or 150 mg esmolol. Induction of anesthesia was accomplished with 4-6 mg/kg thiopental IV followed immediately by the study drug; 1-1.5 mg/kg succinylcholine was given at minute 1. Laryngoscopy and intubation were performed at minute 2 with anesthesia thereafter maintained with 1 MAC (+/- 10%) isoflurane in 60% nitrous oxide in oxygen at a 5 L/min flow for 10 min. Heart rate was recorded every 15 s and blood pressure every minute from induction until 10 min after intubation. Maximum percent increases in heart rate (mean +/- SE) during and after intubation were similar in the placebo (44% +/- 6%), lidocaine (51% +/- 10%), and fentanyl (37% +/- 5%) groups, but lower in the esmolol (18% +/- 5%) group (P less than 0.05). Maximum systolic blood pressure percent increases were lower in the lidocaine (20% +/- 6%), fentanyl (12% +/- 3%), and esmolol (19% +/- 4%) groups than in the placebo (36% +/- 5%) group (P less than 0.05), but not different from each other (P greater than 0.05). Only esmolol provided consistent and reliable protection against increases in both heart rate and systolic blood pressure accompanying laryngoscopy and intubation.