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Propofol or thiopentone as induction agents in romifidine-sedated and halothane-N2O-anesthetized dogs: a preliminary study.

The objective of this paper was to evaluate the use of romifidine as a premedicant in dogs before general anesthesia induced with propofol or thiopentone and maintained with halothane-N2O. Fifteen healthy dogs were anesthetized twice. Each dog received, as preanesthetic protocol, atropine (10 microg/kg, IM) and romifidine (40 microg/kg, IM); induction was delivered with propofol or thiopentone and anesthesia was maintained with halothane and N2O for 1 h. Some cardiovascular and respiratory variables and recovery times were recorded. Induction doses of propofol or thiopentone and the percentage of halothane necessary for maintaining anesthesia were also registered. Thiopentone as an induction agent is more respiratory depressive but is less hypotensive than propofol. Thiopentone reduces further the percentage of halothane necessary for maintaining the anesthesia. However, the quality of recovery is poorer, as the time to extubation is longer and the dogs occasionally had a violent recovery. The combination of romifidine, atropine, propofol, halothane, and N2O appears to be an effective combination for inducing and maintaining general anesthesia in healthy dogs.

Anesthesia, General↗

A comparison of the induction and emergence characteristics of sevoflurane and halothane in children.

This open labelled, randomised, controlled study was designed to compare the induction and recovery characteristics of sevoflurane and halothane anaesthesia in children. Forty American Society of Anaesthesiologist (ASA) physical status class 1 or 2 children (aged 1-10 year, weighed less than 25 kg) scheduled for elective urological procedure lasting less than one hour were allocated randomly to receive either sevoflurane (group S, n = 20) or halothane (group H, n = 20). The induction time in children receiving sevoflurane was significantly shorter than in those receiving halothane (mean (SD) 46 (13.6) second vs 69 (19.4) seconds, p < 0.005). The emergence from anaesthesia was also faster in children receiving sevoflurane than in those receiving halothane (mean (SD) 9 min (4.3 min) vs 21 min (8.9 min), p < 0.001). No major adverse effects were encountered in each group. We concluded that sevoflurane is comparable to halothane in Malaysian children.

Anesthesia, General↗

[The effect of halothane anesthesia on dopamine release induced by apomorphine or haloperidol--an in vivo microdialysis study in rats striatum].

Brain microdialysis was used to study in vivo releases and changes in dopamine (DA) concentration induced by neuroleptics in the rat striatum during halothane anesthesia. Rats were implanted with a microdialysis probe into the right striatum and allowed to move freely. After acquiring steady state of DA and metabolites concentrations, apomorphine 50 micrograms.kg-1 or haloperidol 200 micrograms.kg-1 was administered intraperitoneally with or without 1.5% halothane anesthesia for 1 h. Halothane anesthesia showed no effect on the decrease of DA induced by apomorphine, but halothane antagonized the increase of DA induced by haloperidol. Administration of haloperidol produced an increase in metabolites of DA and it was unchanged by halothane. Malignant syndrome is a well known complication caused by interaction of neuroleptics and anesthesia. The results of the present investigation suggest that the mechanism of malignant syndrome might be associated with the dopaminergic activity.

Anesthesia, Inhalation↗

The depressant effect of halothane and sodium thiopental on the spontaneous and evoked activity of dorsal horn cells: lamina specificity, time course and dose dependence.

The effects of halothane and sodium thiopental on dorsal horn cell unit activity were studied in the lumbar spinal cord of decerebrate, low thoracic spinal cats. Both halothane (0.5, 1 and 1.5%) and sodium thiopental (2.5, 5 and 10 mg/kg) depressed, in a dose-dependent manner, the spontaneous firing frequency of cells in Rexed laminae I, V and VI and the evoked firing frequency of cells in laminae I and V. They, however, had no effect on cells in lamina IV. The maximum depression of cell activity occurred 5 to 8 minutes after inhalation of halothane and 2 to 3 minutes after the intravenous administration of sodium thiopental. The recovery of cell activity occurred within 15 to 30 minutes after discontinuation of halothane and within 10 to 30 minutes after intravenous administration of sodium thiopental. The depressive effect of halothane and sodium thiopental, both primarily hypnotic anesthetics, on lamina VI cells is in contrast to our previous finding that morphine sulfate, nitrous oxide and ketamine hydrochloride, primarily analgesic agents, had no significant effect on this lamina.

Animals↗

Effects of halothane and isoflurane on the contraction, relaxation and energetics of rat diaphragmatic muscle.

BACKGROUND: The inotropic effects of halogenated anaesthetics on diaphragmatic muscle remain a matter of debate. Their effects on its relaxation are poorly understood, although diaphragmatic relaxation is recognized as an important physiological process that may interfere with diaphragmatic performance, fatigue and arterial blood flow. METHODS: The effects of halothane and isoflurane (1 or 2 x minimum alveolar concentration [1 or 2 MAC]) on contraction and relaxation of rat diaphragm muscle strips (n = 40) were studied in vitro from force-velocity curves obtained at various loads from isotonic to isometric conditions. From these curves we determined the peak power output and the curvature. Data are mean (SD) percentage of baseline values. RESULTS: At I MAC, isoflurane and halothane induced no significant inotropic and lusitropic effects. At 2 MAC, isoflurane induced a negative inotropic effect (active force, 93(5)% of baseline). Halothane and isoflurane induced a significant decrease in the peak power output at 2 MAC (88(8) and 86(9)% of baseline; P < 0.05), without significant changes in the curvature of the force-velocity curve. At 2 MAC isoflurane under high loads and halothane under low loads induced moderate negative lusitropic effects. CONCLUSION: Halothane and isoflurane induced very moderate inotropic and lusitropic effects, suggesting that the decrease in diaphragm function observed in vivo is not related to a direct effect on diaphragmatic contractility.

Anesthetics, Inhalation↗

Sources of variability in halothane and caffeine contracture tests for susceptibility to malignant hyperthermia.

In vitro contracture tests for susceptibility to malignant hyperthermia (MH) were performed in 96 patients according to the protocol of the European MH Group. In addition, tests were performed with halothane 0.44 mmol l-1 and 0.66 mmol l-1, and caffeine 2 mmol l-1, each added as a single bolus dose to fresh specimens. For all tests the size of contractures were recorded, and for the diagnostic tests the halothane and caffeine threshold concentrations were determined (i.e. the minimal concentrations eliciting a contracture of 0.2 g). The caffeine specific concentration (CSC, i.e. the concentration increasing force 1.0 g) and the % increase with caffeine 2 mmol l-1 were calculated from the dose response curves. Various diagnostic criteria in use by the North American MH Group were applied, and diagnostic outcome compared with the result obtained by the protocol of the European MH Group. Thirty-five patients were susceptible to MH (MHS), 33 were non-susceptible (MHN), and 28 had equivocal results of the tests (MHE). Additional tests were made in 34 MHS, 32 MHN, and 26 MHE patients. Contractures elicited by bolus addition of halothane or caffeine were significantly larger than those observed following the same dose of drug added cumulatively (P less than 0.05). Contractures greater than or equal to 0.7 g following halothane 3% (bolus dose) were seen in 78% of MHS patients and 18% of MHN patients, A CSC less than 4 mmol l-1 was elicited in 86% of MHS and 30% of MHN patients, whereas an increase in force greater than or equal to 4% or greater than or equal to 7% was seen in 71% and 34% of MHS patients, respectively, and in none of the MHN patients. Using the criterion of greater than or equal to 0.7 g in the halothane test and greater than or equal to 4% increase in the caffeine test gave the best agreement between diagnostic outcome with the European and North American protocols: All 34 MHS patients (100%) were positive to one or more tests, but so were eight of 32 MHN patients (25%), giving an overall diagnostic agreement of 88%. We conclude that, in our laboratory, the results obtained with the two major protocols for investigation of MH susceptibility are not identical. Patients surviving fulminant MH, however, react abnormally to nearly all the tests. For validation and possibly further standardization of the tests each laboratory must investigate a large number of normal controls and as many patients surviving fulminant MH as possible.

Adolescent↗

[Comparative study in pediatric inhalation anesthesia. Clinical characteristics and anesthetic complications with halothane and isoflurane].

OBJECTIVES: Comparative study of clinical characteristics and complications during induction, maintenance, and recovery in pediatric inhalational anesthesia between two commonly used fluoride agents (halothane and isoflurane). MATERIAL AND METHODS: We studied 66 children aged 1 month to 13 years undergoing general anesthesia for short lasting surgery who were divided into two groups of 33 patients each one: Isoflurane group and halothane group. Induction and maintenance anesthesia was performed with the corresponding inhalant agent. Parameters measured were duration of unconsciousness, time elapsed for intubation and recovery, heart rate, arterial blood pressure, and incidence of complications. RESULTS: Children anesthetized with isoflurane showed a shorter period of unconsciousness (1.55 +/- 0.11 min) than those anesthetized with halothane (1.91 +/- 0.12 min); whereas that the time required for intubation was significantly more prolonged (8.94 +/- 0.51 and 6.57 +/- 0.32 min, respectively). The incidence of complications was higher in the isoflurane group, mainly expressed as laryngeal spasm during the induction period. Both groups of patients showed a similar hemodynamic behaviour, although diastolic arterial pressure during maintenance anesthesia was significantly lower with isoflurane. Anesthesia recovery was faster and more predictable with isoflurane than with halothane. CONCLUSIONS: Anesthetic agent isoflurane is less appropriate than halothane for induction in pediatric anesthesia due to a high incidence of complications, specially laryngeal spasm.

Administration, Inhalation↗

Urinary and biliary excretion of metabolites of halothane in dogs.

To determine the urinary and biliary excretion of metabolites of halothane in dogs, 12 beagles were anesthetized with halothane either at 0.5 MAC (minimum alveolar concentration) for 1 hr or at 1.4 MAC for 4 hr. Urine and bile were then collected for 11 days following the anesthesia. The concentrations of inorganic fluoride in the urine and bile were measured with a fluoride electrode and an ion meter. The concentration of total fluoride containing organic fluoride also was measured in the same manner after conversion of the organic fluoride to an inorganic form by combustion. The concentration of trifluoroacetic acid (TFA) in the urine was measured by ion chromatography and that in the bile by gas chromatography. Over 80% of all the fluoride was excreted in the urine as organic fluoride in both groups. While the fraction of TFA in the organic fluoride in the bile was about 30% in both groups, that in the urine was 40% in the 0.5 MAC group and 65% in the 1.4 MAC group. Therefore, it was concluded that the organic fluoride compounds, the metabolites of halothane, and in particular TFA, were excreted mostly into the urine. The extent of metabolism of halothane decreased from 7.6% in the 0.5 MAC group to 4.9% in the 1.4 MAC group. The urinary excretion rate of TFA, however, was not affected by the concentration of inspired halothane.

Animals↗

The effect of halothane, isoflurane, sevoflurane and propofol infusion on renal function after coronary artery bypass surgery.

Renal insufficiency after cardiac surgery is associated with increased mortality, morbidity, and length of stay in the intensive care unit. We investigated the effect of isoflurane, halothane, sevoflurane and propofol anesthesia on perioperative renal function following elective coronary artery surgery. The medical records of 224 patients, in the Hacettepe University Medical Faculty Hospital who had undergone cardiac surgery in one year, were retrospectively reviewed. 65 (29%) patients received isoflurane, 68 (30%) patients received halothane, 64 (29%) patients received sevoflurane, and 27 (12%) patients received propofol infusion as part of maintenance anesthesia for coronary artery bypass surgery. Patient characteristics (age, sex, preoperative ejection fraction), operative data (duration of CPB, duration of operation, number of distal anastomoses, usage of diuretic, intraoperative crystalloid and blood transfusion), intraoperative urinary output, preoperative and postoperative (6th hours and 24th hours) BUN and plasma creatinine levels, were not statistically significant between and within groups. Intraoperative inotropic agent (dopamine) was used in 8 (12.3%) patients in the isoflurane group, in 10 (14.7%) patients in the halothane group, in 11 (17.2%) patients in sevoflurane group and in 9 (33.3%) patients in the propofol group. Postoperatively fluid and blood transfusion, postoperative drainage, urinary output, diuretic usage were smiliar between the four groups (p>0,05). Inotropic agent was used in 8 (12.3%) patients in the isoflurane group, in 9 (13.2%) patients in the halothane group, in 16 (25%) patients in the sevoflurane group and in 7 (25.9%) patients in the propofol group. It is concluded that, halothane, isoflurane, sevoflurane and propofol infusion anesthesia as part of anesthesia maintenance for elective coronary artery bypass surgery does not affect early postoperative renal functions.

Aged↗

Effect of halothane anesthesia and trifluoroacetic acid on protein binding of benzodiazepines.

The in vitro effect of the halothane metabolite, trifluoroacetic acid, on the protein binding of three different benzodiazepines (diazepam, lorazepam and midazolam) has been investigated. Furthermore, protein binding of these drugs was studied in serum from patients under the effect of halothane anesthesia (1-2.5%; 2.5 h). Trifluoroacetic acid, 4 mmol/l, displaced diazepam and midazolam from serum and produced a marked increase in the free percentage, but did not influence lorazepam binding. Moreover, 48 h after the end of halothane anesthesia, there were changes in protein binding of diazepam (3.9 +/- 0.3% at 48 h vs. 3.3 +/- 0.3% before halothane anesthesia; p less than 0.05). It can be concluded that halothane anesthesia (1-2.5%; 2.5 h) may temporarily potentiate the pharmacological effect of diazepam in the postoperative period following anesthetic procedures.

Adult↗

[Effect of sho-saiko-to (xiao-chai-hu-tang) on hepatic injury induced by halothane in rats].

The etiology of halothane induced hepatitis is unknown. This study investigated effect of oral administration of Sho-saiko-to on hepatic injury induced by exposure to 1.1% halothane under hypoxic condition (FIO2 = 0.12) for 2 hr in rats. Serum transaminase, histological score and area of necrosis were examined in rats treated with Sho-saiko-to (900 mg.kg-1) before and after halothane exposure. Twenty-four hours following halothane exposure, serum transaminase levels were significantly depressed; the level of sGOT was significantly lower in rats with treatment of Sho-saiko-to (211 +/- 34 IU.l-1) than in rats without treatment (264 +/- 42 IU.l-1) (P less than 0.05), and the level of sGPT was significantly lower in rats with treatment of Sho-saiko-to (144 +/- 20 IU.l-1) than in rats without treatment (215 +/- 46 IU.l-1) (P less than 0.01). Histological score in rats treated with Sho-saiko-to was significantly lower (3.8 +/- 0.6) than in rats without treatment (4.5 +/- 0.7) (P less than 0.05). The area of centrilobular necrosis was significantly lower in rats with treatment of Sho-saiko-to (21.2 +/- 8.7%) than in rats without treatment (34.5 +/- 12.7%) (P less than 0.05), too. These results indicate that Sho-saiko-to inhibits the hepatic necrosis and functional disorder following exposure to halothane.

Animals↗

[Effects of halothane and barbiturate on hepatic circulation and hepatic oxygen metabolism during hypoxia in dogs].

Hepatic oxygen metabolism and the hepatic energy charge were assessed in 21 mongrel dogs receiving 1 to 1.5 MAC of halothane or thiamylal (20-30 mg.kg-1.hr-1) intravenously while inhaling graded hypoxic mixtures (FIO2 0.21-0.08). Hepatic blood flow was measured using electromagnetic flowmetry: hepatic oxygen delivery and consumption were calculated from measured hepatic blood flow and oxygen content in hepatic arterial, portal venous blood and hepatic venous blood. In the hypoxia-halothane group, portal venous blood flow (FIO2 0.15-0.10), portal venous oxygen content (FIO2 0.10-0.08) and hepatic oxygen consumption (FIO2 0.08) significantly decreased compared with the hypoxia-thiamylal group. Arterial ketone body ratio (AKBR), which indicates the mitochondrial energy charge level, decreased with the development of hypoxia, and in the hypoxia-halothane group, the decrease of AKBR was significantly greater than in the hypoxia-thiamylal group at FIO2 0.08. The serum catecholamine levels, epinephrine and norepinephrine, increased in both groups at FIO2 0.08. In the hypoxia-halothane group, however, the increase of norepinephrine was significantly higher than in the hypoxia-thiamylal group at FIO2 0.08. These results suggest that, compared with halothane, thiamylal could suppress the exaggerated reaction to hypoxic hypoxemia, maintain hepatic circulation and hepatic oxygen metabolism and therefore maintain the hepatic mitochondrial redox state in better condition.

Animals↗

A comparison of cerebral blood flow reactivity to CO2 during halothane versus isoflurane anesthesia for carotid endarterectomy.

The effects of isoflurane or halothane on cerebral blood flow (CBF) reactivity to changes in arterial carbon dioxide tension (PaCO2) during carotid endarterectomy were compared using the intravenous method of 133Xe-CBF determination. Patients, aged 65 +/- 3 yr (mean +/- SE), received O2 and N2O (1:1) and either 0.75% isoflurane (n = 7) or 0.5% halothane (n = 7). Patient demographic and clinical data were similar for both groups and followed the expected strata of patients with ischemic cerebrovascular disease. Measurements were made during the period of temporary bypass shunting. In the isoflurane group, increasing PaCO2 from 33.3 +/- 1.4 to 43.4 +/- 1.3 mm Hg resulted in a significant (P less than 0.05) increase in CBF from 21 +/- 1 to 35 +/- 4 mL.100 g-1.min-1. In the halothane group, increasing PaCO2 from 31.1 +/- 1 to 39.4 +/- 1.6 mm Hg resulted in a significant increase in CBF from 26 +/- 3 to 37 +/- 3 mL.100 g-1.min-1. Mean CBF reactivity to changes in PaCO2 (mL.100 g-1.min-1.mm Hg-1) was 1.74 +/- 0.39 for isoflurane and 1.78 +/- 0.4 for halothane (not significant), corresponding to a relative change of 4.8% +/- 0.8% and 5.2% +/- 1.3% per mm Hg, respectively. There is no significant difference between halothane and isoflurane in their effects on CO2 reactivity in the mildly hypocapnic to normocapnic range.

Aged↗

[The stress reaction in the recovery phase from halothane and isoflurane anesthesia].

This study was undertaken to investigate the influences of halothane and isoflurane as well as different extubation techniques on the endocrine stress response during recovery from general anesthesia. Forty patients scheduled for herniorrhaphy and cholecystectomy were randomly allocated to 4 groups: 20 received halothane and 20 received isoflurane anesthesia. Within the halothane and isoflurane groups, 10 patients each were extubated during anesthesia (1/2 MAC) and a further 10 had awake extubation. Premedication, induction of anesthesia, and intraoperative anesthetic management were standardized in all groups. Plasma levels of endocrine stress parameters as well as mean arterial pressure (MAP), heart rate (HR), and arterial oxygen saturation (SaO2) were measured at nine time points up to 60 min after extubation. Biometric data and duration of operation and anesthesia were comparable in all groups. In the recovery period, epinephrine levels were higher in the isoflurane groups than in the halothane groups (P = 0.02). With respect to time course, earlier and more marked increases of epinephrine, norepinephrine, and antidiuretic hormone (ADH) levels were observed in the isoflurane groups compared to the halothane groups (P less than 0.01), representing the more rapid elimination of isoflurane. The sympathoadrenergic stress response was more pronounced in patients with extubation during anesthesia than in those with awake extubation: epinephrine levels were slightly higher and group levels of norepinephrine were significantly increased (P = 0.02). No influence of the extubation techniques was observed on ADH, ACTH, and cortisol levels or on MAP, HR, or SaO2. In summary, extubation during anesthesia did not reduce the endocrine stress response. It is concluded that awake extubation should be preferred unless the operation or the patient's condition requires extubation during anesthesia.

Adult↗

Biotransformation of halothane in guinea pig liver slices.

The biotransformation of halothane was studied using liver slices. Precision-cut Hartley male guinea pig liver slices (1 cm diameter; 250-300 microns thick) were incubated in sealed roller vials containing supplemented Krebs-Henseleit buffer at 37 degrees C under different O2 tensions (2.5, 21, and 95%). After a 1-hr preincubation, halothane was vaporized in the vial producing a 1.9 mM medium concentration. Halothane metabolites (Br-, trifluoroacetic acid, F-) were measured at 2, 4, and 6 hr. Viability of the incubated slices was verified by determining intracellular K+ content and levels of cytochrome P-450, which were maintained under 95% O2 atmosphere but decreased with lower O2 tensions (2.5%). The highest fluoride production was 300 +/- 22 pmol/mg slice weight/6 hr at low O2 tension (2.5%). Defluorination decreased with increasing O2 tension to undetectable levels under 95% O2. Production of the oxidative metabolite, trifluoroacetic acid, was highest at 95% O2 (2.35 +/- 0.17 nmol/mg slice weight/6 hr). Trifluoroacetic acid production decreased with decreasing O2 tension. Br- production was the highest at 21% O2 (1.8 +/- 0.13 nmol/mg slice weight/6 hr). Production of Br- was not dependent on the O2 tension. The guinea pig slices are capable of biotransforming halothane (oxidative/reductive); therefore, this in vitro system appears suitable for studying the biotransformation of halothane.

Animals↗

[The effect of halothane, enflurane and isoflurane on resistance and compliance in patients with asthma or chronic obstructive lung diseases].

In order to test the hypothesis that halothane is more effective and safer than enflurane and isoflurane in patients with reactive airway disease, a clinical trial was performed to compare these three agents in patients with asthma or chronic obstructive pulmonary disease (COPD). METHODS. After obtaining institutional approval and informed consent, 31 patients with bronchial asthma or COPD were studied (FEV1 less than 65% of FVC); all patients underwent extensive surgery of the paranasal sinuses. Premedication consisted of i.m. atropine and promethazine; anesthesia was induced with diazepam, fentanyl, etomidate, and succinylcholine and maintained with pancuronium and 50% N2O in O2 together with one of the volatile agents, halothane, enflurane, or isoflurane, selected at random. Patients were mechanically ventilated. On the basis of respiratory pressures, volumes, and flows, inspiratory (Rin) and expiratory (Rex) resistance and compliance (C) were calculated after induction (control), 15 min after the addition of the volatile agent (1.25 MAC), every 15 min during the surgical procedure, and at the end of the operation. RESULTS. In 1 case, airway resistance increased markedly a few minutes after administration of isoflurane. The results obtained in this patient were not included in the evaluation of the data. There were no statistically significant differences in the preoperative data or control values of Rin, Rex, and C among the three groups (n = 10 each). With the respective inhalational agents, Rin increased maximally between 3% (halothane) or 8% (enflurane) and 21% (isoflurane), Rex between 16% (halothane, enflurane) and 29% (isoflurane). For the most part, however, these changes were not statistically significant as compared with controls. Intergroup comparisons failed to reveal any statistically significant differences either. In all groups C decreased continuously to about 90% of control. DISCUSSION. The results show that in patients with asthma or COPD, airway resistance remains virtually unchanged during surgery and anesthesia under halothane or enflurane anesthesia. With isoflurane, however, the resistance may rise by a slight but not statistically significant extent. Furthermore, marked bronchospastic reactions occurred in 2 patients in the isoflurane group. Thus, the three volatile anesthetics studied were not found to be unequivocally safe and effective in preventing increases in bronchomotor tone. However, pharmacodynamic effects other than those on respiration (e.g., cardiovascular actions, arrhythmogenic threshold, metabolism, toxicity) must additionally be taken into consideration.

Adult↗

Anesthetics and automaticity in latent pacemaker fibers: I. Effects of halothane, enflurane, and isoflurane on automaticity and recovery of automaticity from overdrive suppression in Purkinje fibers derived from canine hearts.

Knowledge of arrhythmic or antiarrhythmic actions of anesthetics on automaticity of latent pacemaker fibers has relevance to the intraoperative management of patients with bradyarrhythmia due to sinus node dysfunction or heart block. The authors determined the effects of halothane, enflurane, and isoflurane on automaticity and recovery of automaticity from overdrive suppression in canine Purkinje fibers derived from normal hearts. Purkinje fibers were superfused with a modified Krebs' solution (37 degrees C) containing epinephrine (2 or 15 microM) and equilibrated with a 97% O2-3% CO2 gas mixture (control). Transmembrane action potentials (AP) were recorded using standard microelectrode techniques. Purkinje fibers were then exposed to anesthetics at vaporizer settings of 0.75 or 1.5% (halothane), 1.75 or 3.5% (enflurane), and 1 or 2% (isoflurane), which were equivalent to measured superfusate concentrations of 0.22 or 0.47 mM (halothane), 0.44 or 0.94 mM (enflurane), and 0.28 or 0.53 mM (isoflurane). Compared to control, there was no significant effect of either concentration of the anesthetics on upstroke (phase 0) depolarization, AP amplitude or duration (50% repolarization), or maximum diastolic potential. All three anesthetics increased spontaneous rate. The increase in rate with all three anesthetics was due to enhanced diastolic depolarization (rate dV/dt, phase-4 depolarization). Recovery times from overdrive suppression were determined after 30 or 60 s of pacing at drive cycle lengths of 800, 500, and 400 ms and only at higher anesthetic concentrations. Recovery of automaticity was shortened by halothane only in slowly paced fibers exposed to the lower concentration of epinephrine. Under all other conditions recovery times were not affected by halothane.(ABSTRACT TRUNCATED AT 250 WORDS)

Action Potentials↗

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).

Adult↗