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PubMed1977

Inhibition of lipogenesis by halothane in isolated rat liver cells.

1. Halothane at clinically effective concentrations [2.5 and 4% (v/v) of the gas phase of the incubation flask] was found to inhibit significantly lipogenesis from endogenous substrates, e.g., glycogen, or from added lactate plus pyruvate. This was accompanied by a decrease in the ratio of the free [NAD+]/[NADH] of the mitochondrion and the cytoplasm, as shown by the [3-hydroxybutyrate]/[acetoacetate] ratio and the [lactate]/[pyruvate] ratio. 2. Acetoacetate or pyruvate decreased the inhibitory effect of halothane and restored lipogenesis to control rates. They were reduced rapidly by 3-hydroxybutyrate dehydrogenase or lactate dehydrogenase respectively, with the concomitant oxidation of NADH and the generation of NAD+. 3. These results suggest that the mechanism by which halothane inhibits lipogenesis from glycogen or lactate is by inhibition of the oxidation of NADH; this results in inhibition of flux of carbon through pyruvate dehydrogenase and a shortage of acetyl-CoA for fatty acid synthesis. Thus when NADH acceptors are added in the presence of halothane, the concentration of mitochondrial NAD+ is raised so that the flux of carbon through pyruvate dehydrogenase increases and lipogenesis is restored.

Acetoacetates↗
PubMed1983

Effect of halothane on metabolism of 5-hydroxytryptamine by rat lungs perfused in situ.

The effect of halothane (2-bromo-2-chloro-1,1,1-trifluoroethane) on the uptake of 14C-labelled 5-hydroxytryptamine (5-HT) and its metabolism to 5-hydroxyindol-3-ylacetic acid (5-HIAA) was investigated in rat lungs perfused in situ. The rate of accumulation of 14C-labelled 5-HIAA in the tissue, monitored as an index of 5-HT metabolism, was linear with time, displayed saturation kinetics and remained stable for at least 180 min of perfusion. Exposure of the lungs to halothane (4%) for 60 min reversibly reduced production of 5-HIAA through an increase in the apparent Km for metabolism of the amine from 1.45 to 3.52 microM (P less than 0.001); the anaesthetic had no effect on the Vmax. of the process. The magnitude of the inhibition increased with time of exposure to the anaesthetic. Halothane exposure did not alter the distribution of [3H]sorbitol or [14C]5-HT, pulmonary vascular resistance, levels of ATP or the kinetics of amino acid transport in the tissue. Inhibition of protein synthesis by cycloheximide did not mimic the effect of the anaesthetic. These observations, together with those made in lungs exposed to inhibitors of 5-HT uptake and metabolism, were consistent with a halothane-mediated inhibition of 5-HT uptake, which did not appear to involve non-specific changes in membrane permeability.

Animals↗
PubMed2000

The effect of halothane and isoflurane on plasma cytokine levels.

The aim of this study was to investigate the effect of halothane vs. isoflurane on cytokine production during minor elective surgery. Forty adult patients, ASA I-II were randomly allocated to receive halothane or isoflurane. Venous samples for interleukin (IL)-1beta, IL-2, IL-6, tumour necrosis factor-alpha (TNF-alpha) and interferon-gamma (IFN-gamma) were taken before anaesthesia, before incision, at the end of anaesthesia and 24 h postoperatively. In both groups, IL-6 and TNF-alpha levels remained low throughout the study period. Before incision, in both groups IL-1beta and IFN-gamma showed a decrease (p<0.01 for IL-1beta in isoflurane group and p<0.05 for the others) compared with pre-induction. By the end of anaesthesia and surgery, IL-1beta had increased significantly (p<0.05) and IFN-gamma had decreased significantly (p<0.05) in both groups compared with pre-incisional levels. By 24 h postoperatively in both groups, IL-1beta had decreased significantly (p<0.05), whereas IFN-gamma had increased significantly (p<0.05) compared with the end of anaesthesia and surgery level. Pre-incisionally, IL-2 increased in the halothane group (p<0.01), whereas it decreased significantly in the isoflurane group (p<0.001) compared with the pre-induction level. By the end of anaesthesia and surgery and by 24 h postoperatively, IL-2 had decreased significantly in the halothane group (p<0.001), whereas it increased significantly in the isoflurane group (p<0.001) compared with pre-incision and end of anaesthesia and surgery levels, respectively.

Adult↗
PubMed1996

The inhibition of serotonin evoked bovine coronary artery contraction by halothane, isoflurane and sevoflurane is endothelium-independent.

The present study was designed to determine the direct effects of halothane, isoflurane and sevoflurane on the bovine epicardial coronary artery as well as their mode of action. We chose serotonin as the vasoconstrictor because it also causes endothelium-dependent relaxation of coronary arteries. Isolated spiral strips of bovine epicardial coronary artery with and without endothelium were suspended for isotonic contraction recordings in Tyrode's solution. KCl (80.4 mM) solution induced maximal contraction, regarded as the reference value (100%). The muscle strips were then exposed to increasing concentrations of serotonin from 10(-8) to 10(-4) M in the presence and absence of 1.5 MAC halothane, isoflurane or sevoflurane. All three drugs attenuated serotonin-evoked contraction in the coronary artery strips both those strips with and without endothelium (P < 0.05-0.001). However, there were no significant differences in the attenuation of serotonin-induced contraction of the strips, both with and without endothelium, in each drug group. The attenuation potency of halothane was more than that of isoflurane and sevoflurane. The results demonstrate that halothane, isoflurane and sevoflurane attenuate contractile responses evoked by serotonin in bovine epicardial coronary artery both with and without endothelium.

Anesthetics, Inhalation↗
PubMed1996

Marked increases in heart rate associated with sevoflurane but not with halothane following suxamethonium administration in children.

The changes in heart rate and arterial blood pressure following the administration of suxamethonium in healthy children (mean age 3.8 +/- 0.3 years) during inhalational induction with either sevoflurane (n = 22) or halothane (n = 19) were studied. Heart rate 60s following suxamethonium administration increased significantly in the sevoflurane but not in the halothane group. In the halothane group, four children required intravenous (i.v.) atropine as as result of bradycardia. None of the children in the sevoflurane group developed bradycardia following suxamethonium (P < 0.05). Values of oxygenation, ventilation and age corrected minimal alveolar concentration were comparable at all measurement times. The haemodynamic response to the administration of suxamethonium in children anaesthetized with sevoflurane seems to reflect the stimulation of the autonomic ganglia by suxamethonium whereas this positive chronotropic effect is attenuated or reversed by halothane.

Anesthetics, Inhalation↗
PubMed1998

Endocrine and metabolic responses in sheep during halothane and pentobarbitone anaesthesia with dobutamine infusion.

The study investigated the stimulus to pituitary-adrenocortical activity (PACA) during halothane anaesthesia. Groups of six sheep were anaesthetized with thiopentone/halothane (TH group), acepromazine/thiopentone/halothane (ATH group) or pentobarbitone (P group). Dobutamine was infused in the TH and ATH groups to prevent hypotension (0.3-1.4 micrograms/kg/min) and in the P group at 0.05 microgram/kg/min. Pulse rate, arterial blood gases and pressure (ABP) were measured and sequential blood samples taken for assay of cortisol, adrenocorticotrophic hormone (ACTH), arginine vasopressin (AVP), glucose and lactate. Pulse rate increased in all groups. Arterial blood pressure decreased by 13% in TH, by 24% in ATH and remained stable in P. All three groups developed hypercapnia and acidosis but were well oxygenated. Cortisol increased in all groups; with ATH the sevenfold rise occurred earlier than with either TH (sixfold rise) or P (fivefold rise). Adrenocorticotrophic hormone changes were as for cortisol but AVP increases were not consistent. Glucose and lactate were stable, but lactate was lowest with ATH. Dobutamine infusion failed to prevent hypotension during halothane anaesthesia and PACA appeared proportional to the hypotension. Dobutamine may have stimulated ACTH and cortisol release after 120 min. Halothane-induced hypotension may cause adrenocortical activity but a direct effect of halothane cannot be ruled out.

Acepromazine↗
PubMed1998

Adrenocortical and metabolic responses to dobutamine infusion during halothane anaesthesia in ponies.

The study investigated whether hypotension in halothane-anaesthetised ponies is the stimulus inducing an endocrine stress response by assessing the effect of maintenance of normotension with a dobutamine infusion. Groups of six ponies were studied. After premedication with acepromazine (0.04 mg/kg) anaesthesia was induced with thiopentone (10 mg/kg) and maintained for 120 min with halothane (group AN). Dobutamine was infused to effect (1.1-4.4 microg/kg/min) to maintain arterial pressure at pre anaesthetic levels. The conscious group (CON) were prepared as for AN and then received only dobutamine infusion 1.0 microg/kg/min for 120 min. Arterial blood pressure, pH, oxygen and carbon dioxide tension, pulse rate, haematocrit, and plasma cortisol, glucose and lactate concentrations were measured before, at 20 min intervals during anaesthesia, and 20 and 120 min after anaesthesia ceased. Blood pressure remained close to control in both groups. The AN group became hypercapnic and acidotic, pulse rate and haematocrit increased, cortisol increased more than twofold and plasma glucose and lactate did not change. All values remained at control in the CON group except for small increases in haematocrit and decreases in pulse rate. Maintenance of normotension during halothane anaesthesia did not blunt the adrenocortical response to anaesthesia nor did the same dose of dobutamine alone increase plasma cortisol. Hypotension appears not to be the sole stimulus to equine adrenocortical activity during halothane anaesthesia.

Adrenergic beta-Agonists↗
PubMed1998

Endocrine and metabolic responses to plasma volume expansion during halothane anesthesia in ponies.

The study was designed to contribute to identification of the stimulus to adrenocortical activity during halothane anaesthesia in equidae. Two groups of six ponies were premedicated with acepromazine before induction of anaesthesia with thiopentone and maintenance for 120 min with halothane in oxygen. In group H Haemaccel modified gelatine plasma replacer was infused (48+/-13 mL/kg) to maintain mean arterial blood pressure (MABP) close to preanaesthetic values. In group DH, blood pressure was maintained close to preanaesthetic levels with a lower dose of Haemaccel (10 mL/kg) combined with an infusion of dobutamine. Measurements were made before anaesthesia, at 20 min intervals during anaesthesia and 20 and 120 min after anaesthesia. MABP and blood gases, pulse and respiratory rates were measured, and blood was withdrawn for assay of cortisol, adrenocorticotrophic hormone (ACTH), glucose and lactate. Ponies in both groups became hyperoxic, hypercapnic and developed a respiratory acidosis; pulse rate increased in both groups but this was more marked in group H. Haematocrit decreased by 50% in H and by 20% in DH. Cortisol and ACTH did not change significantly during anaesthesia in either group and the area under the time curve (AUC(0-140)) was lower in the DH group. Plasma glucose and lactate remained stable. After the H treatment all ponies had a watery nasal discharge and one pony died from endotoxaemia. This investigation demonstrated that the adrenocortical response to halothane anaesthesia in ponies can be ameliorated by manipulation of ABP using plasma expansion with or without inotrope infusion; however, low dose Haemaccel with dobutamine was safer and more practical. It is suggested that, although hypotension is not the sole stimulus to adrenocortical activity during halothane anaesthesia, it may contribute, probably through an effect on tissue perfusion.

Adrenal Cortex↗
PubMed2001

Recovery times and evaluation of clinical hemodynamic parameters of sevoflurane, isoflurane and halothane anaesthesia in mongrel dogs.

In the present study the influence of three volatile agents (halothane, isoflurane and sevoflurane) in oxygen at two concentrations [1.5 and 2 minimum alveolar concentration (MAC)] on non-invasive cardio-respiratory parameters (heart and respirators rates, non-invasive blood pressures at 15, 30, 60 min and after extubation) and on the recovery times (appearance of the first eyelid reflex, emergence time) after clinical anaesthesia was studied. After premedication with fentanyl-droperidol (5 microg/kg and 0.25 mg/kg, intramuscularly) and induction with propofol (5 mg/kg, intravenously) six dogs were randomly anaesthetized for 1 h for a standard neurologic stimulation test. A wide individual variation in respiration rate (induced by an initial hyperpnea) was observed in the 1.5 MAC protocols, without significant differences. Heart rate was significantly lower during 1.5 and 2 MAC halothane when compared to isoflurane and sevoflurane. An increase from 1.5 to 2 MAC induced significant decreases in diastolic (DAP) and mean arterial blood pressure in all groups without significant changes in the systolic arterial pressures. Only DAP in sevoflurane protocol was significantly different at 1.5 and 2 MAC compared to halothane. Time had no significant influences in the non-invasive blood pressures in all protocols. Extubation induced a significant increase of all parameters in all protocols. The time for a first eyelid reflex was significantly longer after 2 MAC compared to the 1.5 MAC protocol. There was no significant difference between the three anaesthetic agents. Although emergence time was longest for halothane at both anaesthetic concentrations, no significant difference in emergence time was observed for the three volatile agents.

Anesthesia Recovery Period↗
PubMed1997

Haemodynamic responses to sevoflurane compared with halothane during inhalational induction in children.

We studied the haemodynamic changes during induction of anaesthesia in 50 ASA I and II children (1-12 yrs) undergoing minor elective surgery. The patients were randomly divided into two groups to receive either halothane (n = 25) or sevoflurane (n = 25) in a mixture of O2 and N2O (40:60) for mask induction of anaesthesia. Induction of anaesthesia was performed with an overpressure technique by administering rapid increases of gas concentrations, in increments of 1% up to 7% for sevoflurane and of 0.5% up to 3% for halothane. Induction was smooth and rapid in both groups but characterized by increases in heart rate and systolic blood pressure up to 20% especially in the sevoflurane group (P < 0.05); these increases in the latter group were significant compared with baseline and the halothane group (P < 0.05). No serious complications were observed. The authors conclude that more children experienced heart rate and blood pressure increases during the early stage of inhalational induction with sevoflurane compared with halothane.

Analysis of Variance↗
PubMed2000

Haemodynamic depression by halothane is age-related in paediatric patients.

The hypothesis that young infants are more sensitive to the haemodynamic depressant effects of halothane compared with older children was tested. One hundred and sixty unpremedicated, ASA physical status I or II paediatric patients without cardiac or pulmonary disease were divided into five age groups: term neonates, 1-6 months, 6-24 months, 2-6 years and 6-12 years. Anaesthetic induction was achieved with halothane in oxygen and air via mask. Vecuronium 0.1 mg.kg-1 was administered intravenously. During normocapnic manual ventilation by mask, endtidal halothane concentration was maintained at either 2xage-specific MAC (Method I) or 1.7% (Method II) in 20 patients in each age group for 10 min. In both Method I and Method II, systolic and mean blood pressure of term neonates and infants aged 1-6 months decreased significantly (P < 0.01) compared with other age groups. The results of this study demonstrate that neonates and young infants are more susceptible to haemodynamic depression during halothane anaesthesia than are older children, confirming clinical experience.

Age Factors↗
PubMed2001

Postoperative behavioural changes in children: comparison between halothane and sevoflurane.

BACKGROUND: A questionnaire, modified from the posthospitalization behavioural questionnaire, was sent to all parents of children under 8 years of age who had elective surgery in the hospital of Lahr during the years 1997 and 1998. The parents were asked about long lasting changes (more than 1 week) in their child's behaviour after surgery. METHODS: The anaesthesia records of all these children were evaluated on the inhalational agent used (halothane or sevoflurane), the type of surgery, the sedative premedication used, the method of inducing anaesthesia and the use of opioids or nonopioids for pain therapy. Four hundred and fifty-eight of 863 parents responded (53.1%) to the questionnaire. Four hundred and twenty-seven children had minor ENT surgery and 31 minor urological surgery. Two hundred and eleven children received halothane and 214 sevoflurane as inhalational agent. RESULTS: The parents of 34 of the 211 children (16.1%) receiving halothane and 55 of 214 children (25.7%) receiving sevoflurane reported postoperative behavioural changes. This difference was highly significant (P=0.015). CONCLUSIONS: We found that the children having sevoflurane anaesthesia were more likely to develop behavioural problems postoperatively than with halothane. The rate of postoperative behavioural changes was not influenced by the type of surgery, the sedative premedication used, the induction technique or the use of opioids or nonopioid pain therapy.

Anesthetics, Inhalation↗
PubMed2001

Propofol as a sole agent for paediatric day care diagnostic ophthalmic procedures: comparison with halothane anaesthesia.

BACKGROUND: Our aim was to study the feasibility of total intravenous anaesthesia with propofol in spontaneously breathing children undergoing ophthalmic procedures. METHODS: Fifty-five children (aged 6 months to 5 years) were randomly allocated to receive either propofol bolus (until loss of eyelash reflex) followed by infusion [group P (n=29)] or halothane 3-4% for induction, followed by 1-2% in 70% nitrous oxide and oxygen via face mask [group H (n=28)]. Dose for induction and maintenance, intraoperative adverse events, time to recovery (on an Observer's Assessment of Alertness/Sedation Scale, 5 at each level) and duration of procedure were recorded. All children in both groups, were anaesthetized successfully. RESULTS: 4.0 +/- 0.7 mg x kg(-1) and 5.1 +/- 1.0 mg x kg(-1) of propofol were required for loss of eyelash reflex and tolerance of the ophthalmic speculum, respectively. An infusion rate of 8.3 +/- 1.7 mg x kg(-1) x h(-1) was needed for maintenance of anaesthesia; 3.4 +/- 0.5%, 3.6 +/- 0.4% and 1.4 +/- 0.4% halothane was needed for induction, tolerance of the eye speculum and maintenance of anaesthesia, respectively. Induction and recovery were significantly faster with halothane compared with propofol [induction - 38.3 +/- 6.6 s (group H)/60.9 +/- 15.2 s (group P) (P < 0.001); recovery 12.8 +/- 4.6 min (group H)/27.0 +/- 23.3 min (group P) (P < 0.001)]. Apnoea, coughing and breath-holding were seen only in group H. Group P had significantly higher incidence of involuntary movements (minor degree) (n=6) (P < 0.01). CONCLUSIONS: Propofol is a feasible option for paediatric diagnostic ophthalmic procedures with the advantage over halothane of providing complete access to the eye.

Ambulatory Surgical Procedures↗
PubMed2002

Sevoflurane versus halothane: effect of oxycodone premedication on emergence behaviour in children.

BACKGROUND: Clinical studies have provided conflicting conclusions about whether the frequency of emergence agitation is increased in children following sevoflurane anaesthesia. The purpose of the study was to determine a frequency and duration of agitation with halothane and sevoflurane anaesthesia and whether oxycodone premedication affected the incidence of emergence agitation in children. METHODS: We measured and compared halothane and sevoflurane recovery in 130 patients using a 5-point scale measuring emergence behaviour every 10 min during the first 60 min of recovery or until discharge. RESULTS: We used this 5-point scale to assess the presence or absence of emergence agitation and found a frequency of emergence agitation of more than 40% in children who received halothane and sevoflurane anaesthesia. CONCLUSIONS: Oxycodone reduced the frequency of agitation in children who received halothane, but not in the children who received sevoflurane anaesthesia.

Anesthetics, Inhalation↗
PubMed2001

Effects of isoflurane, enflurane, and halothane on skeletal muscle microcirculation in the endotoxemic rat.

PURPOSE: The cardiovascular effects of volatile anesthetics during sepsis sets patients at high risk for hemodynamic deterioration. We compared the microcirculatory alterations in skeletal muscle under anesthesia with isoflurane, enflurane, and halothane in an endotoxemic rat preparation. MATERIALS AND METHODS: Twenty-one Sprague-Dawley rats under continuous hemodynamic monitoring and intravital microscopy of the spinotrapezius muscle were studied during two level lipopolysaccharide (0.2 mg/kg and 2 mg/kg) induced sepsis. The effects of equianesthetic concentrations (1.5 minimum alveolar concentration [MAC]) of either isoflurane [n:7], enflurane [n:7], or halothane [n:7] on microcirculatory vasoregulation were measured and histopathologic changes were evaluated. RESULTS: During low-dose endotoxemia, arteriolar vasodilation under isoflurane was nearly abolished (P < .05). At high-dose endotoxemia, this lack of vasodilatory effect was similar (P < .05). Animals receiving 1.5 MAC of enflurane during low-dose endotoxin presented a significant decrease in arteriolar diameter by -11.3 (+/-2.9%), this response was less during high-dose endotoxemia (-7.0, +/-2.9%). Halothane caused pronounced vasoconstriction by -20 (+/-3.7%) during low-dose endotoxemia and moderate but significant constriction during high-dose endotoxemia (-7.9, +/-2.6%). CONCLUSIONS: Isoflurane, enflurane, and halothane exert significantly different effects on vasoregulation of skeletal muscle arterioles in the endotoxemic rat.

Anesthetics, Inhalation↗
PubMed1999

Skeletal muscle damage following halothane anaesthesia in the domestic fowl: plasma biochemical responses.

The effects of a short period (10 minutes) of halothane anaesthesia upon skeletal muscle have been examined in broiler chickens. Integrity of the muscle membrane was assessed by measurement of plasma activities of intracellular enzymes. Creatine kinase activity was greatly increased during the first 12 hours post-anaesthesia and remained elevated for at least 48 hours. Lactate dehydrogenase activity exhibited a similar pattern which was less pronounced. Halothane anaesthesia induced transient hypercapnic acidosis and hypokalemia and increased corticosterone secretion but there was no significant effect upon deep body temperature. It is proposed that halothane may act directly upon skeletal muscle, perhaps influencing intracellular calcium homeostasis, to alter membrane permeability and increase enzyme efflux reflecting a degree of post-anaesthetic muscle damage. The transient changes in electrolyte and acid-base balance may contribute to these effects. Precautions should be taken to minimise the incidence or extent of halothane induced myopathy in birds particularly in rapidly growing broiler chickens where susceptibility may be increased.

Anesthesia↗
PubMed2001

Cardiorespiratory and endocrine effects of endogenous opioid antagonism by naloxone in ponies anaesthetised with halothane.

Halothane depresses cardiorespiratory function and activates the pituitary-adrenal axis, increasing beta endorphin. In horses, beta endorphin may enhance the anaesthetic-associated cardiorespiratory depression and mortality risk. The authors studied endogenous opioid effects on cardiorespiratory function and pituitary-adrenal activity in halothane-anaesthetised ponies by investigating opioid antagonism by naloxone. Six ponies were anaesthetised three times (crossover design). Anaesthesia was induced with thiopentone and maintained with 1.2 per cent halothane for 2 hours. Immediately after induction, naloxone was administered either intravenously (0.5 mg kg(-1)bolus then 0.25 mg kg(-1)hour(-1)for 2 hours) or intrathecally (0.5 mg) or was replaced by saline as control. Pulse and respiratory rates, arterial blood gases, cardiac output and plasma cortisol and adrenocorticotrophic hormone (ACTH) concentrations were measured. All groups developed cardiorespiratory depression (40 per cent decrease in cardiac output) and plasma cortisol increased. Plasma ACTH concentration was higher in ponies treated with intrathecal naloxone. Endogenous opioids may inhibit ACTH secretion, attenuating the stress response to halothane anaesthesia in equidae.

Adrenocorticotropic Hormone↗
PubMed1997

Effects of brazilin on the altered immune functions in the early phase of halothane intoxication of C57BL/6 mice.

To investigate the effects of brazilin on the altered immune functions in the early phase of halothane intoxication in mice, several immune functions were investigated. Halothane was found to alter the immune functions which lead to hepatitis by autoimmune-mediated process. Based on the fact that immunomodulation at an initial step of autoimmune diseases is effective to prevent or control the diseases, in the present study the effects of brazilin on the altered immune functions in the early phase of halothane intoxication of C57BL/6 mice were investigated. By the treatment of halothane, delayed type hypersensitivity (DTH) and mitogen (ConA, LPS) induced proliferation of splenocytes were significantly increased and suppressor cell activity and mixed lymphocyte reaction (MLR) were decreased in C57BL/6 mice. But IgM plaque forming cells (PFCs) were not significantly changed. All the parameters tested were changed in homing patterns by the treatment with brazilin. But brazilin significantly increased IgM PFCs to higher than the normal level.

Animals↗