Doses of epinephrine causing arrhythmia during enflurane, methoxyflurane and halothane anaesthesia in dogs.

The arrhythmogenic dosage of epinephrine, administered by constant intravenous infusion, was measured in five dogs during enflurane, methoxyflurane and halothane anaesthesia. While premature ventricular contractions were observed in only one of five dogs with enflurane and methoxyflurane, epinephrine-induced arrhythmias were seen in all animals during halothane anaesthesia. Epinephrine dosage and the resultant increase in mean arterial blood pressure at which arrhythmias occurred during halothane anaesthesia were significantly less (p less than 0.05) than with the other anaesthetics. These observations indicate that enflurane and methoxyflurane, as compared to halothane, possess relatively less arrhythmogenic potential as sensitizing agents in the presence of increased circulating catecholamines.     

Comparison of the requirements for hepatic injury with halothane and enflurane in rats

A rat model of enflurane-associated hepatotoxicity was compared with the halothane-hypoxia (HH) model (adult male rats, phenobarbital induction, 1% halothane, 14% O2, for 2 hr). The enflurane-hypoxia heating (EHH) model involved exposing phenobarbital-pretreated male adult rats to 1.5-1.8% enflurane at 10% O2 for 2 hr with external heating to help maintain body temperature. Exposure to either anesthetic without temperature support led to a decrease in body temperature of 7-9 degrees C, while heating the animals during anesthesia resulted in only a 0.5-2 degree decrease. Reducing the oxygen tension to 10% O2 combined with heating the animals during exposure produced significant decreases in the oxidative metabolism of both halothane and enflurane as compared to exposures of 14% O2. The same conditions also caused a significant increase in the reductive metabolism of halothane, indicating that a severe hepatic hypoxia or anoxia occurs during anesthesia at 10% O2 with external heating. The time course of lesion development in the HH model paralleled results obtained with an oral dose of CCl4: gradual progression of necrosis up to 24 hr. EHH resulted in a classic hypoxic/anoxic injury with elevated serum glutamate pyruvate transaminase values and a watery vacuolization of centrilobular hepatocytes immediately after exposure. The HH model required phenobarbital pretreatment of the rats for expression of hepatic injury; EHH did not. Heating of the animals during anesthesia exposure was necessary for enflurane-induced hepatoxicity but had little effect on the HH model. Exposure to 5% O2 without anesthetic mimicked EHH in both requirements for and type of hepatic injury.     

Effects of Respiratory Acidosis on the Arrhythmia Threshold During Fluroxene and Halothane Anesthesia

Hypercarbia was induced in 12 patients anesthetized with either halothane or fluroxene in an inspired concentration of approximately 1.3 MAC (1% halothane and 4-5% fluroxene). The six patients receiving halothane anesthesia responded to hypercarbia with a pronounced tachycardia, an increased arterial pressure and an electrocardiographically monitored threshold level for ventricular arrhythmias at a Paco2 level averaging 98 mmHg. The six patients receiving fluroxene anesthesia responded to hypercarbia with both tachycardia and hypertension, but in spite of an average Paco2 level of 109 mmHg, no ventricular arrhythmias could be provoked. It is therefore suggested that within the non-narcotic level of hypercarbia a threshold level for cardiac arrhythmias does not exist under fluroxene anesthesia.     

Anesthetics and Automaticity of Dominant and Latent Pacemakers in Chronically Instrumented Dogs: IV. Dysrhythmias after Sinoatrial Node Excision

Background: Subsidiary atrial pacemakers assume control after sinoatrial (SA) node excision, and anesthetic-catecholamine interactions can produce severe bradycardia during isoflurane anesthesia. We hypothesized that epinephrine enhances atrial, atrioventricular junctional, and ventricular dysrhythmias after SA node excisions in dogs and that inhalation anesthetics would facilitate such dysrhythmias.

Methods: In eight dogs, SA nodes were excised and epicardial electrodes implanted at the atrial appendages, at the His bundle, and along the sulcus terminalis. Site of the earliest atrial activation and incidences of nonatrial beats were determined in the conscious state, with methylatropine, with epinephrine, and during halothane, isoflurane, or enflurane anesthesia.

Results: After SA node excision, a stable, regular subsidiary atrial pacemaker rhythm resulted. Epinephrine and halothane shifted the site of earliest activation to more remote atrial sites. Epinephrine-induced ventricular escape was increased by all anesthetics tested, but atropine prevented ventricular escape. Epinephrine-induced His bundle (atrioventricular junctional) and premature ventricular beats were increased by halothane and enflurane. After SA node excision, ventricular escape occurred as a result of epinephrine-anesthetic interactions, especially during anesthesia with isoflurane.     

Succinylcholine-induced increases in plasma catecholamine levels in humans

Given the hypothesis that interaction of succinylcholine with nicotinic receptors releases endogenous catecholamines, plasma levels of epinephrine and norepinephrine were determined in anesthetized and manually ventilated patients immediately before and 2 min after intravenous administration of succinylcholine. Anesthesia was induced with intravenous thiopental (3-4 mg/kg) followed by the administration of nitrous oxide and oxygen (1:1) and 0.5-1.0% halothane. Stimulation of the patients was avoided. Succinylcholine (1 mg/kg) or metocurine (0.3 mg/kg) was injected intravenously and ventilation was controlled without intubation. Plasma norepinephrine levels increased from 301 pg/ml to 491 pg/ml (SEM = +/- 19 pg/ml, P less than 0.01, N = 5) 2 min after the injection of succinylcholine; the increase in plasma epinephrine was not statistically significant. The time course of catecholamine elevation was studied in three additional patients. The increase of norepinephrine occurred immediately after the injection of succinylcholine, peaked (647 +/- 67 pg/ml) around the third minute, and disappeared by the 10th min. The increase in epinephrine was less marked. Plasma levels of catecholamines did not change after the injection of metocurine (N = 2). The possibility that succinylcholine stimulates nicotinic receptors on the postganglionic sympathetic terminals is discussed. We propose that the elevation of plasma norepinephrine might contribute to the development of early adverse cardiovascular reactions to succinylcholine.     

Anesthetics and Automaticity of Dominant and Latent Atrial Pacemakers in Chronically Instrumented Dogs: III. Automaticity after Sinoatrial Node Excision

Background: Management of patients with sinus node dysfunction must consider the stability of subsidiary pacemakers during anesthesia and treatment with antimuscarinic or sympathomimetic drugs. Baroreflex regulation of atrial pacemaker function is known to contribute to the interactions between inhalation anesthetics and catecholamines. Sinoatrial (SA) node excision can be a model for intrinsic SA node dysfunction. Subsidiary atrial pacemakers are expected to emerge after SA node excision, but they may respond differently to humoral and neural modulation. Isolated and combined effects of epinephrine and methylatropine should help characterize subsidiary pacemaker function during anesthesia with halothane, isoflurane, and enflurane.

Methods: In eight dogs, SA nodes were excised and epicardial electrodes implanted at the atrial appendages, the His bundle, and along the sulcus terminalis. Spontaneous pacemaker automaticity and subsidiary atrial pacemaker recovery time were measured in the conscious state, in the presence of methylatropine, with 1 and 2 micro gram *symbol* kg1 *symbol* min sup -1 epinephrine and during 1.25 and 2 MAC halothane, isoflurane, and enflurane.

Results: After SA node excision, a stable and regular subsidiary atrial pacemaker rhythm emerged. Each anesthetic prolonged subsidiary atrial pacemaker recovery times. This prolongation was greater in the presence of methylatropine. Without methylatropine, isoflurane and enflurane, but not halothane, further enhanced the baroreflex-mediated negative chronotropic effects of epinephrine, whereas with methylatropine, each anesthetic reduced the direct positive chronotropic effects of epinephrine.     

Cardiac Arrhythmias in Non-intubated Children during Adenoidectomy. A Comparison between Enflurane and Halothane Anaesthesia

The incidence of cardiac arrhythmias, heart rate, blood pressure, capillary perfusion and end-tidal CO2 tension were studied in 167 healthy children 1-12 years of age undergoing adenoidectomy (n = 82) and myringotomy (n = 85) during enflurane and halothane anaesthesia. The incidence of cardiac arrhythmias was significantly lower during myringotomy than during adenoidectomy. In children undergoing adenoidectomy the incidence of arrhythmias was 38.9% during enflurane anaesthesia and 86.6% during halothane anaesthesia (P less than 0.001). In the halothane group ventricular arrhythmias were observed in 19 patients (41.3%) but only in one child (2.8%) in the enflurane group. The ventricular arrhythmias seen during halothane anaesthesia were unifocal in six patients and multifocal in five and classified as ventricular tachycardia in eight children. Heart rate was increased by about 40% at the onset of ventricular arrhythmias. The heart rate remained unchanged with enflurane anaesthesia during surgery, which may reflect a decreased sympathomimetic activity. It is suggested that the low incidence of ventricular arrhythmias during enflurane anaesthesia may be explained by the combination of a reduced sympathomimetic activity and a lowered susceptibility of the myocardium to the actions of endogenous catecholamines.     

Catecholamine and Endocrine Response in Children During Halothane and Enflurane Anaesthesia for Adenoidectomy

In 28 children undergoing adenoidectomy, plasma concentrations of catecholamines, ACTH and cortisol were measured. Fourteen children were anaesthetized with halothane (seven non-intubated, seven intubated) and 14 with enflurane (seven non-intubated, seven intubated). During undisturbed anaesthesia, plasma catecholamines were significantly higher with halothane than with enflurane (P less than 0.05). Immediately after surgery, catecholamines were increased up to 300% in the halothane groups. In the enflurane groups, however, the catecholamine concentrations remained unchanged. This difference between the two agents, after surgery, was statistically significant (P less than 0.01 for intubated and P less than 0.001 for non-intubated children). Fifteen minutes postoperatively no difference was found in plasma concentrations between the groups. In all four groups, plasma concentrations of ACTH and cortisol increased similarly during the procedure. It was concluded that plasma catecholamines were higher during halothane than during enflurane anaesthesia in children undergoing adenoidectomy. This difference may be caused by a stimulating effect of halothane on the endogenous catecholamine release. This increased sympathomimetic response during halothane anaesthesia was correlated to the incidence of ventricular arrhythmias previously found with this agent during adenoidectomy.     

Renovascular hypertension: effect of halothane and enflurane

Male Wistar rats were anesthetized at 6 weeks of age and a silver clip placed around the renal artery to produce renovascular hypertension. The rats were allowed to grow on a normal sodium diet for the next 6-9 weeks. Using diethyl ether anesthesia, arterial and venous cannulae were placed and the animals allowed to awaken in restraining cages. The group of rats was divided into three groups: awake (n = 7), halothane 1.3 vol% (n = 9), and enflurane 2.2 vol% (n = 8). The protocol consisted of a 1-h control awake period, 1 h of stable anesthesia (one group received no anesthesia), and 30-min iv infusion of saralasin, a competitive inhibitor of angiotensin II. Plasma renin activity (PRA) and plasma catecholamines were measured after 1 h of stable anesthesia and after the saralasin infusion. In additional rats treated identically, radiolabelled microspheres were used to measure cardiac output and regional blood flows during halothane (n = 7) or enflurane (n = 6) anesthesia. Principal responses were as follows: mean arterial pressure (MAP) was 193 +/- 4 mmHg awake and decreased to 114 +/- 3 mmHg and 135 +/- 3 mmHg with halothane and enflurane, respectively. Saralasin decreased MAP in the awake group to 176 +/- 3 mmHg and to 69 +/- 3 mmHg and 96 +/- 5 mmHg with halothane and enflurane, respectively. PRA in the awake rats was 7.24 +/- 1.3 ng X ml-1 X h-1. PRA increased with halothane but decreased with enflurane. Plasma catecholamines were decreased markedly by saralasin and by both anesthetic agents.(ABSTRACT TRUNCATED AT 250 WORDS)     

Cortisol levels during enflurane anesthesia in man

Serum cortisol levels were determined in 44 patients who underwent hysterectomy under enflurane or under halothane anesthesia by means of a radioimmunoassay technique. Of the 44 patients, in 21 anesthesia was maintained by enflurane and d-tubocurarine and 23 patients maintenance of anesthesia was carried out by halothane and d-tubocurarine. Blood samples for serum cortisol estimations were obtained from each patient before induction of anesthesia, 10 min. after induction, 10 min. after skin incision, at the end of the operation and in the ward on the fourth postoperative day. Cortisol levels increased in both groups at the end of the operation with a significantly higher mean value in the enflurane group (p less than 0.05) compared to that of the halothane group.     

Halothane, enflurane and isoflurane anaesthesia for adenoidectomy in children, using two different premedications

In 48 children subjected to adenoidectomy, comparisons of airway problems, heart rates, cardiac arrhythmias, ventilation and stress hormone reactions were studied during halothane, enflurane and isoflurane anaesthesia. Sixteen children were anaesthetized with either of the three agents and eight patients in each group received diazepam 0.25 mg kg-1 and atropine 0.015 mg kg-1 rectally (DA) as premedication and the remainder diazepam 0.5 mg kg-1, morphine 0.15 mg kg-1 and scopolamine 0.01 mg kg-1 (DMS) rectally. All children were intubated and breathing spontaneously. Equianaesthetic inspired concentrations of halothane, enflurane and isoflurane were used. Airway problems were of the same magnitude during halothane and isoflurane anaesthesia but were less frequent with both agents compared with enflurane anaesthesia. DMS reduced the number of airway reactions in all groups. Respiratory rates were uninfluenced by anaesthesia, intubation and surgery during enflurane anaesthesia. Cardiac arrhythmias were less frequent with enflurane and isoflurane than with halothane. Plasma ACTH and cortisol were similar with all three agents. During induction of anaesthesia in the DA-premedicated halothane group, however, plasma catecholamines were higher than in the group which received DMS, in contrast to the findings during enflurane and isoflurane anaesthesia. The DMS premedication decreased the response of plasma ACTH, cortisol and plasma catecholamines to surgery.     

Effects of Prolonged Anesthesia with Enflurane or Halothane on Renal Function in Dogs

Elevated serum inorganic fluoride levels (60–300 μmol/l), maintained over 6 h, influenced renal function in beagle dogs. Changes in water reabsorption were seen with an increased urine flow and free water clearance and decreased urinary concentration capacity. Possible nephrotoxicity as an effect of inorganic fluoride production during prolonged enflurane anesthesia was evaluated in a group of beagle dogs. Another group of dogs, anesthetized with halothane in equianesthetic doses, was studied for comparison. Serum inorganic fluoride levels and urinary oxalate excretion were determined and postanesthetic renal morphology was examined. Renal function was evaluated from endogenous clearances and concentration capacity before and after anesthesia. In the enflurane group, serum inorganic fluoride levels peaked at 22.5 μmol/1 at the end of anesthesia and decreased rapidly in the postanesthetic period. Urinary oxalate excretion did not increase. No changes in renal morphology were found. Renal function tests did not reveal any disturbance after enflurane anesthesia. The two anesthetized groups did not differ in any of the parameters studied, except in serum inorganic fluoride levels.     

Is topical application of epinephrine at skin graft donor sites during halothane anesthesia safe?

Topical epinephrine is useful in controlling the bleeding of skin graft donor sites. However, the use of exogenous epinephrine during halothane anesthetization increases the risk of cardiac arrhythmias. This study shows that there is no significant increase in plasma epinephrine levels after topical administration of up to 80 cc of 1:500,000 epinephrine, suggesting that the use of this dose in conjunction with halothane anesthesia is safe.     

Epinephrine-halothane interactions in children

Cutaneous infiltration of dilute solutions of epinephrine for hemostasis during halothane anesthesia can result in ventricular dysrhythmias. Our clinical experience, published reports, and a study comparing piglets with adult swine suggest that children may be less susceptible than adults to dysrhythmias under these conditions. We therefore undertook a prospective survey of heart rate and rhythm in halothane-anesthesized children who received subcutaneous epinephrine for hemostasis. Mass spectrometry was used to quantify end-tidal halothane and to avoid hypercarbia. In 83 children anesthesized with halothane, we continuously recorded ECG, heart rate (HR), end-tidal halothane (ETHalo), and carbon dioxide (ETCO2). The surgeons injected 0.4--15.7 micrograms/kg of epinephrine (in saline or 1% lidocaine) to provide hemostasis at a variety of sites. No child developed a ventricular dysrhythmia. One child had self-limited premature atrial contractions (PAC). Sixty-three children had some increase in heart rate after epinephrine injection, while seven increased their HR 15% or more above pre-injection levels. No relation between any increase in HR and epinephrine dosage, ETHalo, ETCO2, physical status, or age was found by multiple linear regression; however, HR was increased significantly in patients receiving epinephrine in head and neck sites other than the palate. The authors conclude that children tolerate higher doses of subcutaneous epinephrine than adults during halothane anesthesia. The arrhythmogenic dose of epinephrine in children receiving halothane has yet to be determined, but at least 10 micrograms/kg of epinephrine infiltration may be used safely in normocarbic and hypocarbic pediatric patients without congenital heart disease. The presence of PAC and tachycardia emphasize the need for continuous ECG monitoring and caution during halothane anesthesia with epinephrine injection.     

Ventricular arrhythmias after epinephrine injection in enflurane and in halothane anesthesia.

The use of subcutaneous epinephrine during anesthesia is a common clinical practice for providing surgical hemostasis. In studies with 100 patients given either enflurane or halothane, with or without subcutaneous epinephrine, the incidence of ventricular ectopy in patients receiving halothane without epinephrine was 3 percent, while in those given epinephrine with halothane, the incidence was 7 percent. Those who received enflurane alone had no ectopic beats, while ventricular ectopy with enflurane and epinephrine resulted in an incidence of 1 percent. The authors conclude that enflurane anesthesia with concomitant administration of subcutaneous epinephrine is safe, provided the safeguards previously established for use of epinephrine with halothane are observed.     

Suppression of ventricular arrhythmias by volatile anesthetics in a canine model of chronic myocardial infarction

Ventricular tachycardia likely secondary to a reentrant mechanism may be reliably induced by programmed electrical stimulation in dogs 4-6 days after creating a 2-h experimental, occlusion-reperfusion myocardial infarction. The effects of 1.1 and 1.8 MAC halothane, isoflurane, and enflurane on pacing-induced arrhythmias were studied in this model. The ease of initiation of ventricular tachycardia was measured in both awake and anesthetized dogs (n = 18). Excitation thresholds, conduction times, and refractory periods in both normal and infarcted myocardium were also determined to understand changes in the ease of induction of the arrhythmias secondary to anesthetic exposure. Halothane and enflurane administration suppressed the induction of ventricular tachycardia compared with the unanesthetized control (P less than 0.01 for both). During isoflurane anesthesia, there was a trend that was not statistically significant for pacing-induced ventricular tachycardia to be less frequent than during the conscious state (P = 0.11). Halothane and enflurane prolonged refractory periods in both normal and infarcted myocardium, whereas isoflurane had that effect only in normal myocardium. In addition, halothane and enflurane tended to increase refractory periods more than isoflurane in both regions. Conduction times and excitation thresholds were not altered by anesthetic administration. It is concluded that halothane and enflurane suppress inducible ventricular arrhythmias secondary to a prior myocardial infarction. In addition, the increased efficacy of halothane and enflurane as antiarrhythmic agents compared with isoflurane in this model may be related to their greater prolongation of refractory periods.     

Enflurane Anesthesia in Living Donor Renal Transplantation

Two groups of patients undergoing elective living donor renal transplantation were studied during enflurane or halothane supplemented anesthesia. The duration of anesthesia was similar in both groups. The mean administered enflurane dose was 243 vol% min; the corresponding halothane dose was 56 vol% min. In the enflurane group, the mean serum inorganic fluoride level peaked at 21.0 μmol/1 3 h after the end of anesthesia. The inorganic fluoride level in urine produced by the renal graft increased continuously, but did not peak, during the first 24 postanesthetic hours.
The renal graft quickly started to function in all patients in both groups. The frequency of rejection reactions was higher in the enflurane group than in the halothane group. Serum creatinine levels decreased rapidly in both groups. Urine flow was high on the day of transplantation, but normalized on the first postanesthetic day. Renal sodium clearance decreased earlier in the enflurane group than in the halothane group. This difference was statistically significant on the first postanesthetic day. In the enflurane group, the required pancuronium dose was significantly lower than in the halothane group. In one patient in the enflurane group, the serum inorganic fluoride level increased to 37.5 μmol/1.
In this patient renal tubular function may have been affected, but the change was not conclusive since a pronounced rejection of the graft became evident. Since increases in serum inorganic fluoride level approaching 75% of the threshold level for nephrotoxicity in normal kidneys may occur, enflurane should not be routinely used in anesthesia for renal transplantation.     

Cardiovascular effects of acute changes in extracellular ionized calcium concentration induced by citrate and CaCl2 infusions in chronically instrumented dogs, conscious and during enflurane, halothane, and isoflurane anesthesia

To study the cardiovascular effects of low blood ionized calcium ion concentrations [Ca2+] induced by citrate infusion followed by high [Ca2+], induced by CaCl2 infusion awake and during enflurane (2.5% ET), halothane (1.2% ET), and isoflurane (1.6% ET) anesthesia, dogs were chronically instrumented to measure heart rate, aortic, left atrial, and left ventricular (LV) blood pressures, and cardiac output. In conscious dogs low [Ca2+] (decreased 0.35 mM); increased heart rate (HR) and mean aortic pressure (MAP) and decreased stroke volume (SV) and LV dP/dtmax. Low [Ca2+] increased HR during all three anesthetics and decreased LV dP/dtmax except during isoflurane anesthesia. Low [Ca2+] produced more hemodynamic depression during enflurane anesthesia than during anesthesia with halothane or isoflurane increasing left atrial pressure and decreasing MAP and SV. The differences seen were partially related to decreased systemic vascular resistance during halothane and isoflurane anesthesia. In conscious dogs following high [Ca2+] (increased 0.37 mM); only MAP and LV dP/dtmax increased. LVdP/dtmax was also increased by high [Ca2+] during all three anesthetics without a change in MAP. Cardiac output increased during halothane and isoflurane anesthesia but was unchanged during enflurane. It would appear that the hemodynamic sensitivity for the effects of changing [Ca2+] was enflurane greater than halothane greater than isoflurane greater than awake. The results suggest that the effects of changes in [Ca2+] induced by citrate and CaCl2 infusion are modified by the three volatile anesthetics.     

Isoflurane or halothane for cesarean section: comparative maternal and neonatal effects

The maternal and neonatal effects of isoflurane and halothane combined with 50% N2O - 50% O2 were compared in 60 healthy parturients undergoing primary or repeat cesarean section. All patients had rapid sequence induction of anesthesia with sodium thiamylal 4 mg/kg followed by succinylcholine for tracheal intubation. Patients were randomly assigned to one of three groups of 20 each (inspired 0.5% isoflurane, 1% isoflurane or 0.5% halothane), combined with 50% N2O and O2. After delivery, 67% N2O in O2 was used, supplemented by butorphanol. Maternal blood loss did not differ significantly among the three groups and none of the patients developed intraoperative awareness. At the time of delivery, maternal plasma epinephrine levels were significantly above preinduction levels in the 0.5% isoflurane group but unchanged in the other two groups. Neonatal status as ascertained by Apgar scores, cord acid base status and the Neurologic and Adaptive Capacity Scores (NACS) was equally good in the three groups of patients. Serum inorganic fluoride concentrations in the mother after anesthesia were not significantly above preanesthetic levels in any of the groups and there was no biochemical evidence of renal toxicity. In all neonates fluoride ion concentrations in the first voided urine sample were less than 7 mumol/l, a value well below that associated with nephrotoxicity. It is concluded that isoflurane is a safe supplement to N2O - O2 mixture for cesarean section and is a safer alternative to halothane in situations when patients receiving beta-adrenergic therapy require cesarean section since halothane might potentiate arrhythmias caused by beta adrenergic agonists.     

Different effects of halothane and enflurane on diaphragmatic contractility in vivo

We examined the effects of halothane and enflurane on diaphragmatic contractility in 12 anesthetized, mechanically ventilated dogs. The diaphragmatic force was assessed from transdiaphragmatic pressure (Pdi) developed at functional residual capacity against an occluded airway during cervical phrenic nerve stimulation. Animals were randomly assigned to two groups, a halothane group (n = 6) and an enflurane group (n = 6). The Pdi stimulus-frequency relationship was compared at anesthetic levels of 1, 1.5, and 2 MAC (minimum alveolar concentration) in each group. The sequence of changing anesthetic concentration was randomized. In addition, the Pdi-frequency relationship was also compared between 1 MAC of halothane and enflurane in 8 of 12 dogs. In animals anesthetized with enflurane, Pdi significantly decreased with 50- and 100-Hz stimulation in the presence of increasing MAC values, whereas Pdi at 10-Hz stimulation was not affected by the depth of anesthesia. Pdi with 20-Hz stimulation during 2 MAC enflurane also decreased significantly below Pdi levels seen at 1 and 1.5 MAC. By contrast, with halothane there was no difference in Pdi at any of the stimulation frequencies during any of the three levels of anesthesia. There was no statistical difference, however, between Pdi-frequency relationships during 1 MAC of halothane and enflurane in eight animals. From these results, we conclude that halothane does not impair diaphragmatic contractility any more than enflurane does, but enflurane decreases force generation of the diaphragm at high stimulation frequencies in a dose-related fashion. This depressant effect of enflurane occurs mainly through the impairment of neuromuscular transmission and/or membrane excitability.(ABSTRACT TRUNCATED AT 250 WORDS)