Thermogenesis inhibition in brown adipocytes is a specific property of volatile anesthetics

BACKGROUND: This investigation examined the possibility that the inhibitory effect of halothane on nonshivering thermogenesis (heat production) in brown adipocytes is not a universal effect of all anesthetic agents but related to the type of anesthetic. METHODS: Brown adipocytes from hamster were isolated with a collagenase digestion method and incubated with anesthetic agents. The rate of oxygen consumption was measured with an oxygen electrode. The effect of clinically relevant (and higher) doses of anesthetics of different classes on basal and norepinephrine-induced thermogenesis (oxygen consumption) was tested. RESULTS: Two distinct groups of anesthetics could be distinguished: thermogenesis inhibitors and noninhibitors. Thermogenesis inhibitors include volatile anesthetics such as halothane (IC(50), 1.1 mm), ether (IC(50), 20 mm), and chloroform (IC(50), 2.2 mm) (nominal concentrations), but also tribromoethanol (IC(50), 0.6 mm), all inducing inhibition of norepinephrine-induced thermogenesis without affecting the EC for norepinephrine. Thermogenesis noninhibitors include the nonvolatile anesthetics pentobarbital, propofol, ketamine, and urethane, the inhalation anesthetic nitrous oxide, and, notably, also the volatile nonanesthetics (nonimmobilizers) 1,2-dichlorohexafluorocyclobutane and 2,3-dichlorooctafluorobutane; none of these compounds had any effect on norepinephrine-induced thermogenesis at any concentration tested. CONCLUSIONS: There are two distinct classes of anesthetics with regard to effects on thermogenesis, thermogenesis inhibitors and thermogenesis noninhibitors. The results are important for the interpretation of studies in thermal biology in general; specifically, they indicate that conclusions concerning regulation of nonshivering thermogenesis during anesthesia depend on the type of anesthetic used. Of clinical importance is that the volatile anesthetics are inhibitory for nonshivering thermogenesis and thus for an alternative heat production when myorelaxants prevent shivering. As the distinction between thermogenesis inhibitors and thermogenesis noninhibitors corresponds to the distinction between volatile and nonvolatile anesthetics, it may be related to the mode of action of the volatile anesthetics.     

Lack of Nonshivering Thermogenesis in Infants Anesthetized with Fentanyl and Propofol

Background: Sweating, vasoconstriction, and shivering have been observed during general anesthesia. Among these, vasoconstriction is especially important because-once triggered-it minimizes further hypothermia. Surprisingly, the core-temperature plateau associated with vasoconstriction appears to preserve core temperature better in infants and children than adults. This observation suggests that vasoconstriction in anesthetized infants may be accompanied by hypermetabolism. Consistent with this theory, unanesthetized infants rely on nonshivering thermogenesis to double heat production when vasoconstriction alone is insufficient. Accordingly, the authors tested the hypothesis that intraoperative core hypothermia triggers nonshivering thermogenesis in infants.

Methods: With Ethics Committee approval and written parental consent, the authors studied six infants undergoing abdominal surgery. All were aged 1 day to 9 months and weighed 2.4-9 kg. Anesthesia was maintained with propofol and fentanyl. The infants were mechanically ventilated and allowed to cool passively until core (distal esophageal) temperatures reached 34-34.5 degrees Celsius. Oxygen consumption-the authors' index of metabolic rate- was recorded throughout cooling. Because nonshivering thermogenesis triples circulating norepinephrine concentrations, arterial blood was analyzed for plasma catecholamines at [nearly equal] 0.5 degrees Celsius intervals. Thermoregulatory vasoconstriction was evaluated using forearm - fingertip, skin-surface gradients, with gradients exceeding 4 degrees Celsius, indicating intense vasoconstriction. The patients were subsequently rapidly rewarmed to 37 degrees Celsius. Regression analysis was used to correlate changes in oxygen consumption and plasma catecholamine concentrations with core temperature.

Results: All patients were vasoconstricted by the time core temperature reached 36 degrees Celsius. Further reduction in core temperature to 34-34.5 degrees Celsius did not increase oxygen consumption. Instead, oxygen consumption decreased linearly. Hypothermia also failed to increase plasma catecholamine concentrations.     

Thermogenesis Inhibition in Brown Adipocytes Is a Specific Property of Volatile Anesthetics

Background: This investigation examined the possibility that the inhibitory effect of halothane on nonshivering thermogenesis (heat production) in brown adipocytes is not a universal effect of all anesthetic agents but related to the type of anesthetic.

Methods: Brown adipocytes from hamster were isolated with a collagenase digestion method and incubated with anesthetic agents. The rate of oxygen consumption was measured with an oxygen electrode. The effect of clinically relevant (and higher) doses of anesthetics of different classes on basal and norepinephrine-induced thermogenesis (oxygen consumption) was tested.

Results: Two distinct groups of anesthetics could be distinguished: thermogenesis inhibitors and noninhibitors. Thermogenesis inhibitors include volatile anesthetics such as halothane (IC50, 1.1 mm), ether (IC50, 20 mm), and chloroform (IC50, 2.2 mm) (nominal concentrations), but also tribromoethanol (IC50, 0.6 mm), all inducing inhibition of norepinephrine-induced thermogenesis without affecting the EC50 for norepinephrine. Thermogenesis noninhibitors include the nonvolatile anesthetics pentobarbital, propofol, ketamine, and urethane, the inhalation anesthetic nitrous oxide, and, notably, also the volatile nonanesthetics (nonimmobilizers) 1,2-dichlorohexafluorocyclobutane and 2,3-dichlorooctafluorobutane; none of these compounds had any effect on norepinephrine-induced thermogenesis at any concentration tested.     

Postganglionic sympathetic nerve activity in halothane–anaesthetized rats during controlled and spontaneous ventilation

The aim of the study was to compare the effect of halothane anaesthesia on sympathetic nerve discharge in mechanically normoventilated and spontaneously breathing rats. Renal sympathetic nerve activity (rSNA), mean arterial pressure (MAP) and heart rate (HR) were measured in the conscious state and at the inspiratory halothane concentrations of 0.6%, 1.2% and 2.4% in one mechanically normoventilated and one spontaneously breathing group, while a third group was subjected to controlled hypoventilation at 1.2% halothane concentration. Halothane in blood was determined in two separate groups at 1.2%. In an additional group of spontaneously breathing rats, PaCO2 was analysed during consciousness and the halothane concentrations of 1.2% and 2.4%. There was a pronounced decrease in rSNA, MAP and HR at all levels of anaesthesia in the mechanically ventilated rats. However, rSNA, HR and MAP were significantly higher in the spontaneously breathing rats at increasing levels of halothane anaesthesia. Controlled hypoventilation at 1.2% halothane increased the variables significantly. In spontaneously breathing animals, PaCO2 increased significantly during the halothane exposure. The concentration of halothane in blood was significantly higher in the spontaneously breathing rats. Thus, the halothane-induced respiratory depression in the spontaneously breathing rats preserved rSNA during halothane anaesthesia, possibly via CO2-mediated chemoreceptor stimulation.     

Low Concentrations of Halothane Increase Response to a Noxious Thermal Stimulus and Attenuate the Antinociceptive Effect of Intraventricular but Not Intrathecal Morphine

Background: Classically, the first plane of anesthesia is known as the stage of analgesia. Nonetheless, clinical evidence suggests that low doses of inhaled agents might enhance pain perception. The present experiments test the hypothesis that low concentrations of halothane increase response to a noxious thermal stimulus and attenuate the antinociceptive effect of intraventricular morphine via disruption of descending inhibition.

Methods: In the first experiment, the temperature at which rats withdraw their tails from a heat source was measured in animals breathing various concentrations of halothane. In the second experiment, the effect of intraventricular or intrathecal morphine on tail-flick latency was assessed in rats breathing either oxygen or 0.23% halothane.

Results: Low concentrations of halothane decreased the temperature threshold for tail-flick with a maximum effect at 0.06% atmospheres. Halothane attenuated the antinociceptive potency of intraventricular morphine but enhanced the efficacy of intrathecal morphine.     

Ventilation and the oculocardiac reflex

A randomised prospective study was carried out in children undergoing surgery for squint correction, to determine the value of controlled ventilation as a prophylaxis against the occurrence of the oculocardiac reflex. One hundred patients anaesthetised with nitrous oxide/oxygen and halothane were randomly assigned to either ventilated or spontaneously breathing groups of 50 each. Half the patients in each group received glycopyrronium 7.5 micrograms/kg intravenously at the time of induction of anaesthesia. Heart rate, rhythm, blood pressure and end tidal CO2 concentration were monitored throughout. A positive oculocardiac reflex, defined as a fall in heart rate of 20% or more and/or the occurrence of dysrhythmias, was observed in 72% of spontaneously breathing patients and in 100% of ventilated patients not receiving prophylactic intravenous glycopyrronium. The incidence of a positive reflex in patients receiving glycopyrronium was 10% (4 and 16% respectively in spontaneously breathing and ventilated patients). It is concluded that controlled ventilation is of no value as a preventive measure against the occurrence of the oculocardiac reflex in patients undergoing squint surgery and that prophylaxis is safely achieved with the use of intravenous glycopyrronium.     

Anesthesia for removal of inhaled foreign bodies in children

BACKGROUND: Foreign body aspiration may be a life-threatening emergency in children requiring immediate bronchoscopy under general anesthesia. Both controlled and spontaneous ventilation techniques have been used during anesthesia for bronchoscopic foreign body removal. There is no prospective study in the literature comparing these two techniques. This prospective randomized clinical trial was undertaken to compare spontaneous and controlled ventilation during anesthesia for removal of inhaled foreign bodies in children. METHODS: Thirty-six children posted for rigid bronchoscopy for removal of airway foreign bodies over a period of 2 years and 2 months in our institution were studied. After induction with sleep dose of thiopentone or halothane, they were randomly allocated to one of the two groups. In group I, 17 children were ventilated after obtaining paralysis with suxamethonium. In group II, 19 children were breathing halothane spontaneously in 100% oxygen. RESULTS: All the patients in the spontaneous ventilation group had to be converted to assisted ventilation because of either desaturation or inadequate depth of anesthesia. There was a significantly higher incidence of coughing and bucking in the spontaneous ventilation group compared with the controlled ventilation group (P = 0.0012). CONCLUSION: Use of controlled ventilation with muscle relaxants and inhalation anesthesia provides an even and adequate depth of anesthesia for rigid bronchoscopy.     

Prolonged hyporesponsiveness of vascular smooth muscle contraction after halothane anesthesia in rabbits

Halothane diminishes smooth muscle contractility in vascular tissue. In order to further characterize this phenomenon we undertook a series of in vivo and ex vivo experiments. Pressor dose-response curves to the selective alpha 1-adrenergic agonist, phenylephrine, were constructed in groups of rabbits before, during and 2 hr after halothane anesthesia and the dose of phenylephrine that induced a 25 torr increase in mean arterial pressure (ED25) was derived by polynomial regression analysis. ED25 torr increased significantly during halothane anesthesia, and rabbits remained in this insensitive state when the ED25 was assessed 2 hr after anesthesia. The halothane-induced loss of responsiveness was corroborated by ex vivo experiments utilizing aortic rings from halothane-anesthetized rabbits. The maximal contraction to norepinephrine (NE) was significantly lower in halothane-treated aortic rings and only slowly returned to normal by 4 hr. The EC50 (the dose causing a 50% maximal contraction) for NE was significantly greater in aortic rings from halothane-anesthetized rabbits. This loss of sensitivity, reflected by the higher EC50 was not restored by 4 hr of ex vivo incubation in a halothane-free medium. We conclude that halothane induces loss of sensitivity to adrenergic agonists that persists for several hours after termination of the halothane anesthetic.     

Low concentrations of halothane increase response to a noxious thermal stimulus and attenuate the antinociceptive effect of intraventricular but not intrathecal morphine

BACKGROUND: Classically, the first plane of anesthesia is known as the stage of analgesia. Nonetheless, clinical evidence suggests that low doses of inhaled agents might enhance pain perception. The present experiments test the hypothesis that low concentrations of halothane increase response to a noxious thermal stimulus and attenuate the antinociceptive effect of intraventricular morphine via disruption of descending inhibition. METHODS: In the first experiment, the temperature at which rats withdraw their tails from a heat source was measured in animals breathing various concentrations of halothane. In the second experiment, the effect of intraventricular or intrathecal morphine on tail-flick latency was assessed in rats breathing either oxygen or 0.23% halothane. RESULTS: Low concentrations of halothane decreased the temperature threshold for tail-flick with a maximum effect at 0.06% atmospheres. Halothane attenuated the antinociceptive potency of intraventricular morphine but enhanced the efficacy of intrathecal morphine. CONCLUSIONS: Subanesthetic concentrations of halothane may enhance response to a noxious stimulus. The differential effect on intraventricular and intrathecal morphine suggests that this enhancement results from disruption of descending inhibition.     

Halothane anesthesia reduces pulmonary function in the newborn lamb

To study the effects of anesthesia on respiratory function of the neonate, the authors investigated the effect of breathing 100% oxygen and of breathing oxygen plus 0.75 MAC halothane on functional residual capacity, lung and airway resistance, expired minute volume, work of breathing, lung compliance, and blood gases and pH in nine 5-8-day-old, 4.6-7.7-kg lambs. Breathing 100% oxygen increased PaO2 but had no effect on PaCO2, minute ventilation, or lung mechanics. Three-fourths MAC halothane depressed minute ventilation 34% +/- 13% (P less than 0.05) and increased PaCO2 50% +/- 5% (P less than 0.05). Lung and airway resistance increased 59% +/- 26% (P less than 0.05); work of breathing decreased (P less than 0.05); and lung compliance was unchanged. Functional residual capacity was reduced 32% +/- 6% (P less than 0.05), which may be due to loss of diaphragm and intercostal muscle function and to an inability to take deep breaths. The authors conclude that 0.75 MAC halothane significantly impairs the pulmonary function of lambs who breathe spontaneously. Similar changes in human infants could account for the hypoxemia and hypercarbia that often are seen during anesthesia.     

Central leptin gene therapy blocks high-fat diet-induced weight gain,hyperleptinemia, and hyperinsulinemia: increase in serum ghrelin levels

Recombinant adeno-associated virus (rAAV), encoding either rat leptin (rAAV-lep) or green fluorescent protein (rAAV-GFP, control), was injected intracerebroventricularly in rats consuming a high-fat diet (HFD; 45 kcal%). Caloric consumption and body weight were monitored weekly until the rats were killed at 9 weeks. Untreated control rats consuming regular rat diet (RCD; 11 kcal%) were monitored in parallel. Body weight gain was accelerated in rAAV-GFP + HFD control rats relative to those consuming RCD, despite equivalent kcal consumption. At 9 weeks, serum leptin, free fatty acids, triglycerides, and insulin were elevated in HFD control rats. In contrast, rAAV-lep treatment reduced intake and blocked the HFD-induced increase in weight, adiposity, and metabolic variables. Blood glucose was slightly reduced but within the normal range, and serum ghrelin levels were significantly elevated in rAAV-lep + HFD rats. Uncoupling protein-1 (UCP1) mRNA in brown adipose tissue (BAT), an index of energy expenditure through nonshivering thermogenesis, was decreased in rats consuming HFD. Treatment with rAAV-lep significantly augmented BAT UCP1 mRNA expression, indicating increased thermogenic energy expenditure. These findings demonstrate that central leptin gene therapy efficiently prevents weight gain, increased adiposity, and hyperinsulinemia in rats consuming an HFD by decreasing energy intake and increasing thermogenic energy expenditure.     

Oxygen tension-associated changes on secondary immune response in halothane or isoflurane anesthetized mice

The impact that reexposure to anesthetics delivered in 100% oxygen or in synthetic air (21% oxygen/79% nitrogen) has on the secondary humoral immune response to sheep red blood cells was studied. Mice were immunized twice with a 15-day interval and anesthetized immediately after each antigenic challenge with 1.5% halothane or 1.5% isoflurane for 40 min. Halothane in oxygen resulted in increased numbers of IgG-secreting cells (IgG-SC), while halothane in air depressed the response when compared to control mice. In contrast, isoflurane vaporized in oxygen did not affect IgG-SC numbers, while isoflurane given in air lowered the response. Furthermore, neither 100% oxygen, nor the stress of being in an anesthesia chamber breathing synthetic air for 40 min had any immunological effect in non-anesthetized mice.
The inspired oxygen concentration during halothane or isoflurane anesthesia has an effect on the secondary immune response. The effect is different between halothane and isoflurane, possibly due to differences in the extent of their metabolic and pharmacodynamic properties.     

Cardiac rhythm and left ventricular function of infants at 1 MAC sevoflurane and halothane

BACKGROUND: The implementation of sevoflurane in pediatric anesthesia practice led to a decrease in the incidence of cardiac arrest previously reported with halothane. Nevertheless, the effects of sevoflurane on cardiac rhythm and function have not been systematically investigated in infants. Thus, we compared cardiac rhythm and left ventricular function at 1 MAC sevoflurane and halothane anesthesia and investigated the potential benefit effect of atropine. METHODS: Twenty infants ASA physical status I or II were randomly assigned to have anesthesia induced with either sevoflurane (up to 5%) or halothane (up to 1.5%). After insertion of an i.v. line, anesthesia was maintained at 1 MAC sevoflurane (group S) or 1 MAC halothane (group H) with infants breathing spontaneously in 100% oxygen. Cardiac output and contractility were measured by transthoracic echocardiography. Three sets of hemodynamic parameters were averaged prior to and after administration of 20 microg x kg(-1) of i.v. atropine. RESULTS: Infants breathing spontaneously 1 MAC halothane or 1 MAC sevoflurane were found to have comparable hemodynamic parameters. After atropine administration, heart rate and cardiac index (CI) increased significantly in both groups (19.6 +/- 7.6% in group H and 21.3 +/- 13.1% in group S, 18.6 +/- 8.8% in group H and 17.7 +/- 12% in group S respectively). Moreover, atropine induced an increase in left ventricular shortening fraction with no difference between groups. In contrast, only infants in group S presented a significant increase in ejection fraction. CONCLUSIONS: Indices of left ventricular function were comparable between groups with no clinically significant change following atropine administration. The present study confirms the favorable hemodynamic profile of sevoflurane in infants breathing spontaneously at 1 MAC concentration.     

Halothane anesthetic requirements are not affected by aminophylline treatment in rats and dogs

The authors determined the effects of aminophylline on the anesthetic requirements for halothane in rats and dogs. MAC for halothane was determined in rats (n = 24) before and after aminophylline, 100 mg X kg-1 ip, or an equal volume of saline. Because changes in central noradrenergic neurotransmission have been linked to drug-induced changes in the depth of the anesthetic state, we investigated the effect of aminophylline on the turnover of norepinephrine in discrete brain regions of halothane-anesthetized rats. To facilitate testing at steady-state aminophylline conditions and to permit frequent blood sampling, halothane MAC was determined in dogs (n = 7) before and after a therapeutic level of aminophylline (15 +/- 2 micrograms X ml-1) was obtained. Neither in the rats (1.0 vs. 1.0%) nor in the dogs (1.04 +/- 0.14 vs. 1.01 +/- 0.14%) was halothane MAC affected by aminophylline treatment. Commensurate with the lack of change of anesthetic depth, aminophylline treatment did not affect noradrenergic neurotransmission in the brain of halothane-anesthetized rats. Furthermore, the anticipated increase in circulating catecholamines following aminophylline treatment in dogs did not materialize. The authors conclude that halothane anesthetic requirements are not altered by aminophylline treatment, possibly because of the attenuation of the putative sympathomimetic effects of aminophylline by halothane.     

Lack of the mechanoreceptor influences on ventilatory control during halothane anesthesia in humans

Mechanical influences independent of chemoreceptor function on ventilatory control were studied in halothane-anesthetized, artificially ventilated patients using the technique reported by Altose et al. (Respir Physiol 66: 171–180, 1986). Contribution of mechanical factor was indirectly assessed by comparing the values of arterial carbon dioxide tension at which the subjects started breathing efforts during CO₂ loading induced by the following two methods. 1) Partial rebreathing of expired gas and 2) Mechanical hypoventilation (successive decrease in inflation volume). These two maneuvers resulted in a similar rate of increase in end-expiratory carbon dioxide tension. However, contrary to the observation made by Altose et al. in awake volunteers, we found comparable values of ventilatory recruitment threshold for Pa_{CO 2}. Thus, we speculate that halothane anesthesia and/or loss of consciousness impair transmission of afferent information from the lung and/or chest wall musculature. Such effects may be responsible for the depression of load compensatory mechanism during anesthesia.(Kochi T, Ide T, Isono S, et al.: Lack of the mechanoreceptor influences on ventilatory control during halothane anesthesia in humans. J Anesth 6: 387–394, 1992)     

Halothane Impairs the Hemodynamic Influence of Endothelium-derived Nitric Oxide

Background: The endogenous vasodilator endothelium-derived nitric oxide (EDNO) contributes to the regulation of vascular tone and organ perfusion. It has been suggested that some volatile anesthetics may diminish the influence of EDNO and thereby decrease regional blood flow.

Methods: Radioactive microspheres were used to determine regional hemodynamics in rats. The authors tested the hypothesis that halothane inhibits EDNO and, therefore, should diminish the response to nitric oxide synthesis inhibition by NW -nitro-L-arginine methyl ester (L-NAME) compared with either conscious or barbiturate-anesthetized rats.

Results: NW -nitro-L-arginine methyl ester decreased blood flow to the brain by 23% (P < 0.005) in conscious rats to a level similar to that seen with either anesthetic agent. In both conscious and barbiturate-anesthetized rats, L-NAME increased blood pressure (BP) by 24 plus/minus 2 (P < 0.001) and 20 plus/minus 1 (P < 0.001) mmHg and total peripheral resistance (TPR) by 132% (P < 0.001) and 105% (P < 0.001), respectively. In contrast, during halothane anesthesia, both the pressor response (only 7 plus/minus 1 mmHg) and the increase in TPR (only 22%) were greatly diminished (P < 0.001). NW -nitro-L-arginine methyl ester decreased cardiac output (CO) by 47% (P < 0.001) and heart rate (HR) by 28% (P < 0.001) in conscious rats. In barbiturate-anesthetized rats, L-NAME decreased CO by 38% (P < 0.005) and HR by 13% (P < 0.001). In halothane-anesthetized rats, L-NAME changed neither CO nor HR. Thus halothane anesthesia largely eliminated the systemic response to EDNO synthesis inhibition. In conscious rats, L-NAME decreased blood flow to the heart (30%) and kidneys (47%). In barbiturate-anesthetized rats, L-NAME did not alter blood flow to the heart but decreased renal blood flow by 35% (P < 0.005). In halothane-anesthetized rats, L-NAME did not alter blood flow to either the heart or the kidneys. Overall, halothane blunted or blocked the systemic and regional hemodynamic responses to EDNO synthesis inhibition seen in conscious and barbiturate-anesthetized rats.     

Functional decortication lowers ventromedial hypothalamic activation induced by hippocampal neostigmine injection

This experiment tested the effects of cortical spreading depression (CSD) on the ventromedial hypothalamic activity and on the related thermogenesis, both stimulated by an injection of neostigmine in the hippocampus. The firing rate of the neurons of the ventromedial hypothalamus, and the temperature of the interscapular brown adipose tissue and of the colon (T:(IBAT) and T:(C)) were monitored in 24 urethane-anesthetized male Sprague-Dawley rats divided into four groups. These variables were measured before and after hippocampal injection of neostigmine (5 x 10(-7) mol) in the first and second groups or of saline in the third and fourth groups. The hippocampal injection was preceded by CSD in the first and third groups, while CSD was not induced in the second and fourth groups. The same procedure was carried out in the other four groups of six rats each and oxygen consumption was monitored. The results show an increase in the firing rate, T:(IBAT), T:(C) and oxygen consumption after the neostigmine injection. CSD significantly reduces these enhancements. The findings demonstrate that: (i) the activation of ventromedial hypothalamic neurons are involved in the thermogenic changes due to the effects of a neostigmine injection into the hippocampus; and (ii) integrity of cerebral cortex is required for this activation of thermogenesis.     

Pulsus alternans during general anesthesia with halothane: effects of permissive hypercapnia

BACKGROUND: Pulsus alternans is a classic type of abnormal pulse. It can be defined as a regular alternation of pulse amplitude in which runs of weak and strong beats follow each other alternatively without any change in cycle length. It may be a sign of severe decompensated congestive heart failure. The authors infrequently encountered some cases of pulsus alternans during halothane anesthesia with spontaneous respiration in otherwise normal subjects in association with high levels of end-tidal carbon dioxide. This study was conducted to determine if there is any relation between this phenomena and hypercapnia. METHODS: One hundred twenty patients undergoing elective lower extremity surgery were selected. Halothane was used for maintenance of anesthesia, and the patients were allowed to breath spontaneously. The occurrence of pulsus alternans was determined by plethysmographic display of pulse wave and then confirmed by palpation of the radial artery. RESULTS: Ten patients (8.3%) developed pulsus alternans together with elevated levels of end-tidal carbon dioxide (57 +/- 4 mmHg vs. 41 +/- 4 mmHg in patients without pulsus alternans [mean +/- SD]). The pulsus alternans disappeared after switching to controlled ventilation and 15-20% reduction in end-tidal carbon dioxide. During the period of pulsus alternans, vital signs and electrocardiography remained within normal limits. CONCLUSIONS: There may be some relation between occurrence of pulsus alternans and hypercapnia during halothane anesthesia. Pulsus alternans occurs in a small fraction of spontaneously breathing, halothane-anesthetized patients. Although hypercapnia is clearly a factor, the mechanism of this phenomenon is unknown.     

Oxygen Consumption during Surface-Induced Deep Hypothermia under Halothane Anesthesia

The effect of halothane-100% oxygen anesthesia on oxygen consumption was studied in 10 dogs subjected to surface-induced deep hypothermia with 30 minutes of circulatory arrest. The results were compared with previous oxygen consumption data under ether-100% oxygen anesthesia.Low cardiac output, especially during the rewarming period, low Pa02, and a large arteriovenous oxygen difference during rewarming were significantly different in the halothane group, despite identical oxygen consumption in both groups. These differences could not elucidate the exact cause of postoperative motor disturbances associated with 30 minutes of circulatory arrest in the halothane group. The possibility that there was higher oxygen consumption under halothane anesthesia is discussed.     

RAPID INDUCTION OF HALOTHANE ANAESTHESIA IN MAN

The cardiopulmonary and anaesthetic responses of nine healthyvolunteers, breathing concentrations of 1-4% halothane in oxygen,were studied. Supine fasting subjects breathing room air exhaledto residual volume and then inhaled a vital capacity breathof 1, 2, 3 or 4% halothane in oxygen. After a breath-hold of30–90 s they exhaled and then breathed spontaneously thesame anaesthetic mixture for up to 2 min. The electrocardiogram,arterial pressure, heart sounds and arterial oxygen saturation,were monitored, and respiratory gases were analysed by massspectrometry. The maximum effect was seen after breathing 4%halothane. All volunteers were amnesic after the first breathand unresponsive to command after 2 min. Little or no excitementoccurred. A maximum decrease of 12 mm Hg in systolic pressurewas seen while breathing 4% halothane. Bradycardia, hypoxiaand clinically important hypercarbia did not occur. At all inspiredconcentrations of halothane, the end-tidal halothane concentrationincreased rapidly and was 30% of the inspired value after 1min. No volunteer found this technique to be unpleasant. Rapidinduction of general anaesthesia with 2–4 % halothanein oxygen is effective, safe and well accepted by healthy youngadults.