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Background Sevoflurane is a known triggering agent of malignant hyperthermia ( MH). The present study analyzed different effects of sevoflurane on skeletal muscle of MH susceptible and nonsusceptible individuals in vitro and compared the results to the standardized test protocol with halothane and caffeine. A potential influence of a present ryanodine receptor type 1 ( RyR1) mutation was investigated. Methods Muscle bundles of 24 MH-susceptible patients with or without an RyR1 mutation, 35 MH-nonsusceptible and 10 MH-equivocal patients were exposed either to sevoflurane 8 vol% bolus or increasing doses of 2, 4, 6, and 8 vol%. In MH-positive patients, a screening for mutations in the RyR1 gene was performed. Results The in vitro parameters initial length, weight, predrug resting tension, and predrug twitch height did not differ between the groups. Sevoflurane caused significant contractures in MH-susceptible but not in MH-nonsusceptible muscle after increasing doses [1.4 (0.3-6.0) vs. 0 (0-0) mN] and after bolus application [6.9 (2.4-21.4) vs. 0 (0-0) mN]. However, only 50% of the susceptible patients developed contractures ≥ 2 mN after increasing concentrations while 83% did so after rapid bolus administration. Presence of an RyR1 mutation was detected in 36% of the examined MH-positive patients but had no influence on developing contractures. Conclusion Sevoflurane-induced contractures do not reliably detect MH susceptibility on an individual level. Therefore, sevoflurane is no suitable alternative for diagnostic use. Mutation-specific effects regarding contracture sizes after incubation with sevoflurane, halothane, or caffeine were not found. [ABSTRACT FROM AUTHOR]

Background A common form of congenital myotonia, myotonia congenita ( MC), is caused by mutations in the skeletal muscle Cl− channel gene type 1 (CLCN1). Due to the reduced Cl− conductance of the mutated channels, the patients may develop generalized muscle rigidity and hypermetabolism during general anaesthesia. The clinical symptoms resemble malignant hyperthermia (MH), which may lead to mistreatment of the patient. Methods Muscle specimens of ADR mice (an animal model of MC) as well as of human individuals were used and exposed to potent ryanodine receptor type 1 ( RyR1) activators and increasing K+ concentration. Muscle force was monitored by a standardized diagnostic method for MH, the so-called in vitro contracture test. Results Neither muscle of ADR mice nor MC muscle (murine and human myotonic muscle) showed pathological contractures after exposure to the potent RyR1 agonists caffeine and halothane. Increasing concentrations of K+ had a dose-dependent preventive effect on myotonic stiffness. Conclusion We conclude that the adverse anaesthetic MH-like episodes observed in MC patients do not primarily originate from an altered Ca2+ release in skeletal muscle. In MC muscle, this hypermetabolism is facilitated by a (pharmacologically induced) sustained depolarization due to an instable membrane potential. The in vitro results suggest that these patients benefit from tight K+ monitoring because of the membrane potential stabilizing effect of K+. [ABSTRACT FROM AUTHOR]

Background: In a rat closed head trauma model we examined both the time course of lipid peroxidation and the effects of halothane, isoflurane, and sevoflurane on it by analysis of malondialdehyde (MDA) formation. Methods: Animals were divided randomly into five groups: sham-operated (SO), n=18; control-closed head trauma to left frontal pole, n=18; closed head trauma model+halothane, n=18; closed head trauma model+isoflurane, n=18; and closed head trauma model+sevoflurane, n=18. Halothane, isoflurane, or sevoflurane were applied 15 min after trauma for 30 min. Rats were euthanized 1,3, and 5 h after the inhalation agents. Brain tissue samples were taken 5 mm from the left and right frontal poles. MDA was considered to reflect the degree of lipid peroxidation. Results: MDA concentrations were greater in the control, halothane, sevoflurane, and isoflurane groups than in SO animals ( P<0.001). No statistical difference between the hemispheres was found between the halothane, isoflurane, or sevoflurane groups, but MDA levels were lower with isoflurane than in the halothane, sevoflurane, and control groups at 1, 3, and 5 h ( P<0.001). MDA levels were higher as compared with the halothane and sevoflurane groups at 1 h but not at 3 or 5 h ( P<0.001). Conclusion: MDA levels with the isoflurane group were lower than in the other trauma groups, which suggest that isoflurane, given after closed head trauma, might be protective against lipid peroxidation of cerebral injury. [ABSTRACT FROM AUTHOR]

Background: Bronchoactive properties of volatile agents against lung constriction are well established. The purpose of this study was to investigate the ability of halothane (Hal), isoflurane (Iso), sevoflurane (Sev) and desflurane (Des) to alter the lung mechanics in the absence of an airway tone and during acetylcholine (Ach)-induced bronchoconstriction. Methods: Low-frequency pulmonary impedance data ( ZL) were collected from isolated, normo-perfused rat lungs under baseline conditions and following the injection of Ach (0.1 mg/kg) into the pulmonary artery. Measurements were performed without the administration of any anaesthetic agent in the first phase of the experiments and during inhalation without any volatile agent (control group, n = 6) or during inhalation of Hal ( n = 6), Iso ( n = 9), Sev ( n = 6) or Des ( n = 8) at 1 minimum alveolar concentration (MAC). The airway resistance ( Raw) and parenchymal damping and elastance were estimated from the ZL data by model fitting. Results: Under baseline conditions, the basic value of Raw was significantly decreased by Des (− 31.2 ± 3.8%) and Sev (− 18.0 ± 4.5%) administration, whereas Hal and Iso did not have a statistically significant effect on Raw (− 3.3 ± 5.1% and − 8.6 ± 2.4%, respectively). Moreover, all four inhalation anaesthetics prevented the increase in Raw following Ach administration, the findings ranging between − 14.3 ± 11.4% for Hal and − 37.5 ± 10.9% for Sev. Conclusions: Our results on a denervated isolated perfused lung model demonstrate the potential of Des and Sev to decrease the basal airway tone, whereas Iso and Hal are ineffective in this regard. All of these volatile agents markedly protect against Ach-induced bronchoconstriction. [ABSTRACT FROM AUTHOR]

Background: Most of the research efforts to monitor the depth of anaesthesia using the mid-latency auditory evoked potential (MLAEP) signal in humans are based on the detection of the amplitudes and latencies of the signal peaks. Attempts have also been made to combine different time-domain and frequency-domain parameters. A comparison of different parameters is required to identify those which best discriminate the awake state from the anaesthetized state. Methods: Although the sensitivity of MLAEP signal peaks is appreciable in awake and light anaesthesia states, it is reduced considerably at the moderate anaesthesia level, rendering this method unsuitable for predicting the surgical stage of anaesthesia. To overcome this problem, a numerically derived quantity – the morphology index – was used which does not require location of the peaks of the signal, but, at the same time, reflects the changes in both the latency and amplitude of the peaks. AEPs were recorded in the hospital for 18 patients during various states, i.e. awake, induction, unconscious and after regaining consciousness from halothane anaesthesia. The peak latencies, amplitudes, morphology index and peak power frequency (PPF) were calculated. Results: The sensitivity and specificity of PPF (89% and 95%, respectively) were found to be better than those for Pa and Nb peak amplitudes, their latencies and the morphology index. In addition, PPF showed minimum inter-patient variation. The mean value (standard deviation) of this parameter was 26.9 (0.67) during the awake state, decreased to 17.1 (1.2) during the anaesthetized state, and increased again to 26.1 (0.93) when the patients regained full consciousness. Conclusion: PPF is the best of the four studied MLAEP parameters for the clinical characterization of the anaesthetized state during surgery. [ABSTRACT FROM AUTHOR]

Background: Halothane and propofol depress the central nervous system, and this is partly manifested by a decrease in electroencephalographic (EEG) activity. Little work has been performed to determine the differences between these anesthetics with regard to their effects on evoked EEG activity. We examined the effects of halothane and propofol on EEG responses to electrical stimulation of the reticular formation. Methods: Rats ( n= 12) were anesthetized with either halothane or propofol, and EEG responses were recorded before and after electrical stimulation of the reticular formation. Two anesthetic concentrations were used (0.8 and 1.2 times the amount needed to prevent gross, purposeful movement in response to supramaximal noxious stimulation), and both anesthetics were studied in each rat using a cross-over design. Results: Electrical stimulation in the reticular formation increased the spectral edge (SEF) and median edge (MEF) frequencies by approximately 1–2 Hz during halothane anesthesia at low and high concentrations. During propofol anesthesia, MEF increased at the low propofol infusion rate, but SEF was unaffected. At the high propofol infusion rate, SEF and MEF decreased following electrical stimulation in the reticular formation. Conclusions: At immobilizing concentrations, propofol produces a larger decrease than halothane in EEG responses to reticular formation stimulation, consistent with propofol having a more profound depressant effect on cortical and subcortical structures. [ABSTRACT FROM AUTHOR]

McArdle's disease of isolated deficiency in glycogen degradation in skeletal muscles has the potential of creating perioperative anaesthesiological problems; such as hypoglycaemia, rhabdomyolysis, myoglobinuria, acute renal failure and possibly malignant hyperthermia. Eight patients with McArdle's disease were asked about previous surgery, anaesthesia and perioperative problems, and available hospital records were reviewed. Existing literature was reviewed for reports on McArdle's disease and anaesthesia. The eight patients had 35 anaesthesias (23 general anaesthesias, three regional anaesthesias and nine local anaesthesias). Perioperative problems of a non-specific nature were mentioned in three cases of general anaesthesia: two with postoperative nausea/vomiting, and one with an episode of tachycardia and low blood pressure. Three patients were tested for malignant hyperthermia (MH) using the in vitro contracture test (IVCT); two of them with a positive result. The literature search revealed seven case reports of McArdle's disease and anaesthesia. Apart from one report of hyperthermia, pulmonary oedema and rhabdomyolysis; probably not associated with MH, no problems were encountered from the literature search. McArdle's disease does not seem to cause severe perioperative problems in routine anaesthetic care. However, measures for preventing muscle ischaemia and rhabdomyolysis should be kept in mind, as well as the potential for these patients to develop postoperative fatigue, myoglobinuria and renal failure. Although no clinical association with malignant hyperthermia has been established, many of these patients can have a positive in vitro contracture test, and simple prophylactic measures, as with malignant hyperthermia, may be recommended if otherwise not contraindicated. [ABSTRACT FROM AUTHOR]

Previously, we have shown in adult patients that bispectral index score (BIS) values are significantly higher during halothane anesthesia (53–61 units) as compared with those observed during equipotent concentrations of sevoflurane (39–43 units). Because halothane is frequently used in the pediatric setting, we tested the hypothesis that BIS values observed in children might also be higher during general anesthesia with halothane than with sevoflurane. Forty-one healthy, unpremedicated pediatric patients scheduled for elective operations received either halothane or sevoflurane titrated as appropriate for surgical stimulation. During maintenance sevoflurane anesthesia ( n = 20), the mean BIS values and percent end-tidal concentrations were 44 ± 14 and 2.1 ± 0.6, respectively, whereas for the halothane group ( n = 21) the corresponding values were 61 ± 7 and 1.1 ± 0.4, respectively. These findings suggest that BIS values are higher during halothane vs. sevoflurane anesthesia in children, but not in infants [ABSTRACT FROM AUTHOR]

Volatile anesthetics are known to cause diaphragmatic dysfunction using a whole body model. The first aim of the current study was to compare the impairing effect of halothane and sevoflurane on diaphragmatic contractile functions under unfatigued and fatigued conditions. The second purpose was to determine whether phosphodiesterase-III inhibitors can attenuate sevoflurane-potentiated reduction of contractility after fatigue. Using rat-isolated muscle strips, diaphragmatic twitch characteristics and tetanic contractions were measured before and after muscle fatigue, which was induced by repetitive tetanic contraction with or without exposure to halothane (1–3 MAC) or sevoflurane (1–3 MAC). Diaphragmatic functions were further assessed with exposure to 3 MAC sevoflurane in the presence and absence of milrinone, or olprinone. Cyclic adenosine monophosphate (cAMP) concentrations in the fatigued diaphragm were also measured. Halothane (1–3 MAC) or sevoflurane (1–2 MAC) did not induce a direct inotropic effect under unfatigued and fatigued conditions. Sevoflurane at 3 MAC enhanced fatigue-induced impairment of twitch and tetanic tensions. Clinically relevant concentrations of olprinone improved the sevoflurane-induced potentiation of diaphragmatic dysfunction following fatigue, accompanied by restoration of diaphragmatic cAMP levels, although milrinone failed to do so. Our findings suggest that sevoflurane has a greater decreasing effect on diaphragmatic contractility after fatigue than halothane, and that the clinical dose of olprinone surmounts the disadvantage of sevoflurane in various conditions where diaphragmatic fatigue is predisposed. [ABSTRACT FROM AUTHOR]

Isoflurane and halothane act in the spinal cord to blunt ascending transmission of impulses to the brain resulting from noxious stimulation. Because intrathecal picrotoxin (an antagonist at the gamma-aminobutyric acid-A receptor) partially reverses the immobilizing effect of isoflurane and halothane, we hypothesized that the electroencephalographic response to noxious stimulation would likewise be partially reversed by intrathecal picrotoxin. Rats were anesthetized with isoflurane (n = 8) or halothane (n = 8) and a laminectomy performed. Following determination of minimum alveolar concentration (MAC), the electroencephalogram (EEG) was recorded during separate applications of a hindpaw clamp, tail clamp and electrical current to the tail at 0.8 and 1.2 MAC. Picrotoxin was then applied to the exposed spinal cord and the EEG response to noxious stimulation again determined. The EEG was more active during halothane anesthesia than isoflurane (spectral edge frequency for 95% power: 25.6 ± 2.1 Hz vs. 23.1 ± 1.6 Hz, P < 0.05). Noxious stimulation usually caused the EEG to shift to higher frequencies (e.g. for 0.8 MAC halothane, median edge frequency for 50% power: from 7.6 ± 3.1 Hz to 10.7 ± 2.6 Hz, P < 0.05). Picrotoxin minimally affected this response. Noxious stimulation evokes an EEG response that is minimally altered by intrathecal picrotoxin. This suggests that isoflurane and halothane do not have GABAergic actions in the spinal cord that indirectly suppress the EEG response. [ABSTRACT FROM AUTHOR]

The oculocardiac reflex (OCR) may be activated during squint surgery. The aim of this study was to test whether rocuronium 0.4 mg kg−1 could reduce the frequency of OCR, and also whether a single dose of succinylcholine 1 mg kg−1 could affect the frequency of OCR during anesthesia with halothane in a nitrous oxide/oxygen mixture.A total of 161 ASA I children, 3–10 years old, undergoing elective surgery of the medial rectus muscle (MRM) were randomly assigned to three groups. Group R (n = 51), received 0.4 mg kg−1 of rocuronium intravenously before endotracheal intubation. Group S (n = 58) received 1 mg kg−1 of succinylcholine. Group C (controls, n = 52) received no relaxant. Oculocardiac reflex was defined as a reduction in heart rate (HR) >= 15% and/or the appearance of any other arrhythmias, during manipulation of the MRM. Analysis of variance (anova), chi-squared, Kruskal–Wallis, and Student'st-tests were used for statistical analysis;P< 0.05 was considered statistically significant.In group R, OCR occurred in 15/51 (29%) of children, in group S in 31/58 (53%), and in group C in 23/52 (44%) (χ2 = 6.46,P = 0.049). In group R, the incidence of arrhythmias such as nodal rhythms, supraventricular and ventricular premature beats was 6%, compared with 22% in group S and 19% in group C (χ2 = 6.01,P = 0.040). However, there was no reduction in the occurrence of bradycardia (χ2 = 0.16,P = 0.924).,Rocuronium reduced the frequency of OCR, mainly by reducing the incidence of supraventricular and ventricular premature beats. [ABSTRACT FROM AUTHOR]

The diagnosis of susceptibility to malignant hyperthermia (MH) is currently performed on muscle biopsies subjected to halothane-caffeine in vitro contracture tests (IVCTs). There is a consensus on our need to improve the diagnostic potential of IVCTs if we are to maximize the information available for research and diagnosis in MH. This study was designed as a pilot comparative study and we aimed at comparing the ryanodine test and new tests using a combination of ryanodine, halothane and caffeine. One hundred and thirty-two subjects (52 MHS and 80 MHN) were included in this study and new IVCTs were performed in additional muscle biopsy specimens. The contracture time-course was compared considering the onset time of contracture (OT) and the time to reach a 10 mN contracture (10T). Cut-off values were determined using ROC analyses. For the ryanodine test, sensitivity and specificity calculated for OT were 84.6% and 90.4%, respectively, and were better than those obtained using 10T. Combined tests using either caffeine and ryanodine or halothane and ryanodine did provide higher sensitivities (from 85.3 to 93.9%). A better specificity was only observed for the IVC tests combining halothane (cumulated) and caffeine both with ryanodine (93.9% for both). The largest sensitivity was observed when halothane was used as a bolus and combined with ryanodine. The specificity was always larger with the combined tests as compared to the test using ryanodine alone (from 79.1 to 90.9%). This superiority was confirmed, at least in part, when comparing genetic investigations and the results of new tests in a subgroup of subjects. This pilot study showed a clear diagnostic potential for new IVC tests combining halothane, the triggering agent of MH, and ryanodine acting at the calcium release channel, and should be considered as a first step in the investigation of combined tests. [ABSTRACT FROM AUTHOR]

Background: Cytochrome P4502E1(CYP2E1)-mediated oxidation of halothane to a reactive intermediate (trifluoroacyl chloride) that covalently binds to hepatic proteins forming trifluoroacetylated neoantigens is believed to be the initiating event in a complex immunologic cascade culminating in antibody formation and severe hepatic necrosis ('halothane hepatitis') in susceptible patients. Trifluoroacyl chloride may also hydrolyze to the stable metabolite trifluoroacetic acid (TFA). CYP2E1 inactivation by disulfiram or its primary metabolite, diethyldithiocarbamate, inhibits human halothane oxidation to TFA in vitro and in vivo. Nevertheless, disulfiram effects on hepatic protein trifluoroacetylation by halothane in vivo are unknown. This investigation tested the hypotheses that disulfiram prevents halothane-dependent protein trifluoroacetylation in vivo, and that TFA represents a biomarker for hepatic protein trifluoroacetylation.Methods: Rats were pretreated with isoniazid (CYP2E1 induction), isoniazid followed by disulfiram (CYP2E1 inhibition), or nothing (controls), then anesthetized with halothane or nothing (controls). Plasma and urine TFA were quantified by ion HPLC; hepatic microsomal TFA-proteins were analyzed by Western blot.Results: CYP2E1 induction increased both TFA and TFA-protein formation compared with uninduced halothane-treated rats. Disulfiram, even after CYP2E1 induction, nearly abolished both TFA and TFA-protein formation. Pretreatments similarly affected both TFA and TFA-protein formation across all groups.Conclusions: Disulfiram inhibition of CYP2E1-mediated halothane oxidation prevents hepatic protein trifluoroacetylation. Based on the concordance between TFA and TFA-protein formation, TFA appears to be a valid biomarker for TFA-protein formation. Disulfiram inhibition of human halothane oxidation in vivo, previously assessed by diminished TFA formation, probably also confers inhibition of hepatic TFA-protein formation. [ABSTRACT FROM AUTHOR]

Background: Assessment of preload independent left ventricular function with conductance volumetry is traditionally accomplished by inflating a balloon in the inferior caval vein. Our aim was to investigate if a similar change in preload could be achieved by positive pressure ventilation with large tidal volume.Methods: Conductance volumetry generating left ventricular pressure-volume loops was used in seven pentobarbital-anesthetized pigs. Changes in preload recruitable stroke work were studied, comparing the effects of inferior vena cava occlusion (IVCO) or large tidal volume (LTV). Cardiodepression was induced by halothane anesthesia and halothane + phenylephrine, and stimulation by epinephrine infusion.Results: Although the decreasis in left ventricular end diastolic volume was slightly less with LTV (16.5 +/- 1.7 ml, mean +/- SEM) than with IVCO (22.4 +/- 1.7 ml) (P < 0.0001) the PRSW-slopes showed a high degree of correlation (r=0.80, P < 0.0001). Although peak tracheal pressures increased significantly to 27.8 +/- 0.9 mmHg during LTV, esophageal pressures (used as an indicator of pericardial pressure) were unchanged.Conclusions: Positive pressure ventilation with LTV is similar to IVCO in creating transient changes in preload, necessary for assessment of left ventricular systolic function. This observation was valid also during drug-induced cardiac depression and stimulation. The preload recruitable stroke work used for this validation was shown to be a reliable and stable method. [ABSTRACT FROM AUTHOR]

Background: The ryanodine receptor of the skeletal muscle (RYR1) seems to be of outstanding importance in the pathogenesis of malignant hyperthermia (MH). It has been shown that point mutations in the RYR1 gene are strongly associated with the MH phenotype. A correctly determined phenotype is the basic prerequisite for adequate genetic MH screening. In this study we examined only those MH susceptible patients for the presence of potential RYR1 mutations who showed strong pathological muscle responses in the in vitro contracture test (IVCT).Methods: A total of 56 MHS index patients who complied with the following IVCT criteria were included in the molecular genetic investigation: Contracture forces > or =4 mN at a caffeine concentration of 2.0 mmol/l and > or =8 mN at a halothane concentration of 0.44 mmol/l. DNA sequences of exons 2, 6, 9, 11, 12, 14, 15, 17, 39, 40, 45, 46, 102 of the RYR1 gene were analysed by the direct sequencing technique. Furthermore, if an MH mutation was identified in an index patient, all relatives were screened for their family specific RYR1 defect.Results: In 39 index patients an RYR1 mutation was detected: Arg163Cys (n = 2), Asp166Asn (n = 1), Gly341Arg (n = 2), Arg401His (n = 2), Arg614Cys (n = 12), Asp2129Glu (n = 1),Vol2168Met (n = 1), Thr2206Met (n = 9), Ala2428Thr (n = 1), Gly2434Arg (n = 2), Arg2435His (n = 1), Arg2452Trp (n = 1), Arg2454His (n = 4). Three new RYR1 mutations were identified. We found a potential MH mutation in a further 130 relatives of the 39 index patients. Thirty-seven individuals were classified as MHS exclusively by molecular genetic techniques and did not have to undergo the IVCT.Conclusions: The ascertained high rate of successful MH mutation screening (69.64%) is obviously associated with the more clearly defined MHS diagnosis in the IVCT. According to the EMHG guidelines for the molecular genetic detection of MH susceptibility, a positive MH disposition could be determined in numerous persons by a less invasive technique. [ABSTRACT FROM AUTHOR]

Background: Halogenated volatile anesthetics (HVAs) are considered to be inhibitors of nitric oxide synthase (NOS). On other hand, NO mediates the vasodilation produced by HVAs. Thus, both increase and decrease of NO concentration in brain tissues are possible during anesthesia. Previously, we have observed an increase of NO content in rat brain cortex under halothane anesthesia. The goal of this study was to determine whether the observed phenomenon was general for this anesthetic group, if it was specific for brain cortex, and if the NO increase was due changes in NOS activity.Methods: NO scavengers were injected to adult rats 30 min prior to anesthesia. Rats were anesthetized by inhalation of an O2 mixture with volatile anesthetics (1.5% for halothane; 1% for isoflurane, 2% for sevoflurane). After 30 min of anesthesia, rats were decapitated and brain cortex, cerebellum, liver, heart, kidneys and testes were dissected, frozen in liquid nitrogen and subjected to EPR spectroscopy. Nitric oxide content was determined quantitatively based on the intensity of the NO-Fe-DETC complex spectrum and its comparison with the calibration curve.Results: In rats anesthetized with HVAs, we observed a greater than twofold increase of NO content in brain cortex as compared to the nonanesthetized animals. No significant changes were detected in other organs. The NOS inhibitor N(omega)-nitro-L-arginine abolished the increase of NO content in brain produced by volatile anesthetics.Conclusion: The action of volatile anesthetics is coupled with an increase of NO content in the cortex dependent on NOS activity. [ABSTRACT FROM AUTHOR]

Background: Ischaemia-reperfusion injury following tourniquet release is a good in vivo model for evaluating acute conditions. The aim of the study was to investigate the effects of propofol or halothane anaesthesia on oxidative stress by determining malondialdehyde (MDA) levels during knee arthroplasty. Methods: Thirty patients undergoing orthopaedic surgery were divided into two groups. Anaesthesia was induced with either fentanyl 100 μg and propofol 2 mg kg-1 (Group 1) or fentanyl 100 μg and thiopentone 5 mg kg-1 (Group 2) and maintained with infusion of propofol in Group 1 or inhalation of halothane in Group 2. ECG, SpO2, EtCO2, and mean arterial pressure (MAP) were monitored. Venous and arterial blood samples were obtained at different measurement times for MDA and blood gas analyses. Results: There was a significant decrease in MAP in the 1st and 5th minutes after tourniquet release (ATR) when compared with the 5th minute before tourniquet release (BTR) in both groups. Heart rate (HR) increased significantly in the 1st minute ATR in Group 1 only. EtCO2 increased significantly in the 1st and 5th minutes ATR, SpO2 decreased in the 1st minute ATR in both groups. There was a significant decrease in pH and increase in pCO2 at 1, 5 and 30 min ATR in both groups. pO2 values decreased in the 1st minute ATR in Group 1 only and returned to control values at 5 min ATR and decreased at 30 min ATR in the recovery room in both groups. The differences in SaO2 were similar to SpO2. MDA levels decreased before and after release of tourniquet when compared to baseline in both groups. However, there was a statistically significant decrease only in Group 1. Conclusion: Propofol may be a good choice of anaesthetic when an ischaemia-reperfusion injury is anticipated as in orthopaedic surgery requiring a tourniquet, due to its antioxidant properties, but halothane needs further study. [ABSTRACT FROM AUTHOR]

Background: Halothane is known to potentiate catecholamine-induced depression of conduction velocity in Purkinje fibers but not endocardial muscle fibers. The purpose of this study was to examine the interactions of halothane with epinephrine and isoproterenol on canine epicardial conduction velocity at moderately elevated extracellular potassium concentration ([K]0).Methods: Epicardial muscle strips (10x10x2 mm) were superfused with Tyrode's solution containing 4 or 8 mM [K]0 in the presence of 5 microM epinephrine or 1 microM isoproterenol with or without 0.8 mM halothane. Conduction velocity in the longitudinal and transverse directions relative to epicardial fiber orientation was recorded during alternate stimulation in each direction.Results: In the presence of halothane, a change from 4 to 8 mM [K]0 decreased (P< or =0.05) longitudinal and transverse conduction velocities by 26% and 21%, respectively. Isoproterenol alone at 4 and 8 mM [K]0 depressed (P<0.05) both longitudinal and transverse conduction velocities. However, the depression of longitudinal conduction velocity by isoproterenol at 4 mM [K]0 was attenuated by halothane. Epinephrine with or without halothane depressed (P<0.05) both longitudinal and transverse conduction velocities at 8 but not at 4 mM [K]0.Conclusion: The results do not support a synergistic interaction between halothane and epinephrine on myocardial conduction but do demonstrate depression of conduction by epinephrine at 8 mM [K+]0, a potassium ion concentration comparable to those reported following epinephrine infusions. [ABSTRACT FROM AUTHOR]

Background: In preschool children, short-lasting surgical procedures are often performed under combined inhalational and regional anaesthesia with the child breathing spontaneously via a laryngeal mask airway (LMA). Despite widespread use, only limited data are available on haemodynamic, respiratory and metabolic effects of sevoflurane and halothane during LMA anaesthesia.Methods: In an open-label, randomised, controlled study, 49 children (aged 3-8 years) were allocated to receive either sevoflurane or halothane in 60% nitrous oxide. After insertion of the LMA, end-tidal concentrations of sevoflurane or halothane were maintained at 1 MAC with the child ventilating spontaneously throughout the entire procedure. Analgesia was provided by caudal block. Haemodynamic and respiratory parameters were recorded, and capillary blood-gas samples were obtained repeatedly.Results: Changes in heart rate (HR) and systolic blood pressure were similar in both groups during all observed periods, apart from a significantly higher increase in HR during inhalational induction with sevoflurane (P<0.05). Regression slope analysis during anaesthesia revealed a decrease of the respiratory rate of 5 breaths h-1 (P<0.001) and an increase of end-tidal PCO2 and capillary PCO2 of about 0.25 kPa h-1 (P<0.001), with no significant difference between the two groups. Base excess, calculated in capillary blood gas samples, did not change over time (P>0.5) in either group.Conclusions: The use of approximately 1 MAC sevoflurane or halothane in 60% N2O in children breathing spontaneously via LMA resulted in comparable haemodynamic, respiratory and metabolic changes, and clinically relevant deteriorations did not occur during the 65-min study period. [ABSTRACT FROM AUTHOR]

Background: Rocuronium is a non-depolarizing neuromuscular blocking agent with intermediate duration of action and without significant cumulative properties, suitable for continuous infusion. This study was designed to determine the infusion requirements in children under nitrous oxide and fentanyl, halothane, isoflurane or sevoflurane anaesthesia. Methods: Forty children, 3–11 years old, ASA physical status group I or II were studied. They were randomly allocated to receive fentanyl-nitrous oxide, 1 MAC halothane-nitrous oxide, 1 MAC isoflurane-nitrous oxide or 1 MAC sevoflurane-nitrous oxide anaesthesia. Rocuronium, 0.6 mg-1 was used to facilitate endotracheal intubation. Electromyographic response of adductor pollicis to train-of-four (TOF) stimulation, 2 Hz for 2 s, applied to the ulnar nerve at 10-s intervals was recorded using Relaxograph (Datex, Helsinki, Finland). Once the first twitch response (T1) returned to 5%, muscle relaxation was maintained by continuous infusion of rocuronium, adjusted automatically in a closed-loop system to maintain a stable 90–99% T1 depression. The block was considered stable if it changed by no more than 2% over a 10-min observation period. Results: Halothane, isoflurane and sevoflurane groups had lower infusion requirements than the fentanyl-nitrous oxide group (P<0.00075). Rocuronium requirement (mean ± SD) at one hour from the commencement of anaesthesia was 16.7±2.3, 13.6±3.7, 13.1±5.1 and 8.4±1.6 μg · kg-1 · min-1 for children receiving fentanyl-nitrous oxide, halothane, isoflurane and sevoflurane anaesthesia, respectively. Conclusions: The rocuronium infusion rate required to maintain stable 90–99% T1 depression was reduced by approximately 20% with halothane and isoflurane anaesthesia, and by 50% with sevoflurane anaesthesia when compared to fentanyl-nitrous oxide anaesthesia. Significant patient-to-patient variability of infusion rate makes monitoring of neuromuscular transmission necessary. [ABSTRACT FROM AUTHOR]

Background: Halothane and isoflurane affect differently endothelium-dependent and -independent vasorelaxation at 95% O2. In addition, hypoxic vascular response might involve endothelium-dependent and -independent mechanisms. Therefore, we investigated, in rabbit aortic rings, 1) the influence of halothane and isoflurane on vasodilation at 95% O2 and on hypoxic-induced vasorelaxation at 0% O2 and 2) the influence of halothane and isoflurane on endothelium-dependent and -independent post-hypoxic vascular response.Methods: Endothelium-intact and endothelium-denuded rabbit aortic rings were used. Phenylephrine precontracted rings were exposed, at 95% O2, to acetylcholine (ACh, 10(-9) to 10(-4) M) or sodium nitroprusside (SNP, 10(-9) to 10(-4) M) in the presence or absence of anaesthetic at 1 or 2 MAC. Precontracted rings were also exposed to an acute reduction in O2 from 95% to 0% followed by an acute reoxygenation with 95% O2 in the absence or presence of anaesthetic at 1 or 2 MAC.Results: At 95% O2, halothane decreased endothelium-dependent relaxation to ACh, while endothelium-independent relaxation to SNP was decreased only at 2 MAC. Isoflurane did not modify ACh- or SNP-induced relaxation. At 0% O2, neither halothane nor isoflurane altered the hypoxic vascular relaxation. Post-hypoxic response was not changed either.Conclusion: Our results indicate that halothane and isoflurane do not alter vascular hypoxic response in conductance arteries. [ABSTRACT FROM AUTHOR]

Background: Sevoflurane, a potent inhalational anaesthetic agent that is structurally similar to halothane, has some favourable characteristics, but may also be able to trigger malignant hyperthermia (MH) in susceptible patients. The diagnosis of malignant hyperthermia susceptibility relies on the in vitro contracture test on skeletal muscle. The present study was undertaken to investigate whether exposure to sevoflurane of muscles of malignant hyperthermia susceptible (MHS) patients would also cause an abnormal contracture.Methods: Muscle fascicles obtained from three MHS patients, one malignant hyperthermia non-susceptible (MHN) patient, two control patients and one malignant hyperthermia equivocal (MHE) patient were exposed to sevoflurane instead of halothane in the in vitro contracture test, carried out according to the protocol of the European Malignant Hyperthermia Group. The muscle fascicles were surplus to diagnostic requirements. Sevoflurane concentrations in the testbath were measured using a headspace gas chromatographic technique.Results: The kinetics of sevoflurane concentration in the testbath were similar to those of halothane. An in vitro contracture response of 2 mN or more was seen in all four MHS/MHE patients with sevoflurane but not in the three control/MHN patients. The magnitude of muscle contracture in the sevoflurane test was less than in the conventional halothane test at comparable testbath concentrations.Conclusions: Sevoflurane can trigger an abnormal contracture in human muscle in vitro. This is indicative of malignant hyperthermia susceptibility. Exposure to sevoflurane should be avoided in patients thought to be susceptible to malignant hyperthermia. [ABSTRACT FROM AUTHOR]

Background: Our objective was to compare the recovery characteristics of sevoflurane and halothane for short day-case anaesthesia in a specifically limited age group of children 1-3 yr.Methods: Eighty unpremedicated children undergoing day-case adenoidectomy were randomly assigned to receive inhalational induction with either sevoflurane 8% or halothane 5% and nitrous oxide in oxygen (70/30) via a face mask. Tracheal intubation was performed without a muscle relaxant. Anaesthesia was continued with the volatile anaesthetic, adjusted to maintain heart rate and blood pressure within +/-20% of initial values. Recovery was evaluated using a modified Aldrete score, a Pain/Discomfort scale and by measuring recovery end-points. A postoperative questionnaire was used to determine the well-being of the child at home until 24 h after discharge.Results: Emergence and interaction occurred significantly earlier after sevoflurane than halothane but discharge times were similar. More children in the sevoflurane group achieved full Aldrete scores within the first 30 min after anaesthesia, although this group suffered more discomfort during the first 10 min. The amount of postoperative analgesic administered was higher and the first dose given earlier in the sevoflurane group. Postoperative vomiting was more common with halothane, but side-effects in the two groups were otherwise similar in the recovery room and at home.Conclusions: In children 1-3 yr, sevoflurane provided more rapid early recovery but not discharge after anaesthesia of <30-min duration. Apart from more vomiting with halothane and more discomfort during the first 10 min after awakening with sevoflurane, the quality of recovery was similar with the two anaesthestics. [ABSTRACT FROM AUTHOR]

Background: To identify individual factors and combination of factors predictive of reversal time (defined as time from neostigmine administration to train-of-four (TOF) ratio 0.70) from atracurium-induced neuromuscular block, the present study tested the following variables as possible predictors of reversal time: 1) degree of block at the time of antagonism as quantified by first response to TOF or double-burst stimulation (DBS); 2) time from last supplemental dose of atracurium to administration of neostigmine (pre-reversal time); and 3) time from administration of initial atracurium dose to T1 (the magnitude of the first twitch in TOF) recovered to 10% (duration of action of the initial dose of atracurium). Methods: The study population comprised 83 female patients, ASA physical status 1 or 2, anaesthetized with fentanyl, thiopental, halothane and nitrous oxide. Initial and supplemental doses of atracurium were 0.5 mg · kg-1 and 0.15 mg · kg-1, respectively. Evoked responses to TOF or DBS were recorded mechanomyographically. Neuromuscular block was antagonized with neostigmine, 0.07 mg · kg-1, at varying time intervals (6–50 min) after the final atracurium dose. Results: Multiple linear regression analyses testing T1, D1 (the magnitude of the first twitch in DBS), pre-reversal time and duration of action of the initial dose of atracurium, demonstrated that with superficial block, T1 >15%, T1 is the only significant predictor for reversal time. With moderate block, 0< T1 ≤15%, both T1 and duration of action of the initial atracurium dose are significant predictors for reversal time. With profound block, T1=0, duration of action of the initial dose and pre-reversal time are significant predictors for reversal time. Conclusion: 1) T1 is a more important predictor for reversal time from atracurium-induced neuromuscular block than D1; 2) predictors differ with the degree of block: with T1 >15%, T1 is the only significant predictor; with 0< T1 ≤15%, the duration of action of the initial dose and T1 are predictors for reversal time; with T1=0 , the duration of action of the initial dose and pre-reversal time predict reversal time. [ABSTRACT FROM AUTHOR]

Background: The effects of isoflurane and halothane anesthesia on hepatic circulation and oxygen metabolism during hepatolobectomy were investigated in the dog, in an attempt to assess which of the anesthetics was the better one for hepatic resection.Methods: Mongrel dogs (n=24) were divided into two groups and accordingly anesthetized with isoflurane (n=12) or halothane (n = 12). Each test anesthetic was administered in air. Electromagnetic flowmeters were used to measure hepatic arterial and portal venous blood flows 1) before the inhalation of each anesthetic (baseline); 2) 1 h inhalation of 1.5 MAC (minimum alveolar concentration) of each anesthetic; and 3) 1 h after hepatolobectomy with each anesthesia. Measurements of systemic hemodynamics, blood gas tensions, and the arterial ketone body ratio were made at the same time.Results: Isoflurane maintained portal venous, hepatic arterial and total hepatic blood flows better than halothane anesthesia before and after hepatolobectomy. With halothane anesthesia, hepatolobectomy decreased prominently hepatic arterial blood flow. Hepatic arterial and mesenteric vascular resistance increased in the halothane group, but remained constant in the isoflurane group after hepatolobectomy. Hepatic oxygen delivery was significantly suppressed in the halothane group, but did not change in the isoflurane group. No significant difference was found in hepatic oxygen consumption between the two groups, but the arterial ketone body ratio decreased significantly only in the halothane group before and after hepatolobectomy.Conclusion: The present data indicate that isoflurane has less adverse effect than halothane anesthesia on hepatic circulation, oxygen delivery and energy charge in hepatolobectomy cases. [ABSTRACT FROM AUTHOR]

Background: An agitated recovery may occur after inhalation anesthesia. The aim of the present study was to assess the recovery quality after mask anesthesia with either halothane or sevoflurane in children.Methods: Sixty-two children, 8 months to 18 years of age, scheduled for minor surgery, were randomly assigned to receive either halothane or sevoflurane. The patients were premedicated with midazolam and anesthesia was induced i.v. with propofol or by inhalation and maintained with halothane or sevoflurane in N2O/O2 via face mask. Recovery was assessed by a "blinded" observer using a postanesthetic recovery score. Agitation and pain were judged using a visual analog scale. The incidence of vomiting was noted. The day after anesthesia older children and parents of younger children were interviewed about their experience of the anesthesia and recovery period.Results: There were no differences between groups in respect of age, weight, length, or duration of surgery or inhalational gas exposure. Median time from end of administration of inhalational agent to spontaneous eye opening was less after sevoflurane (25 min) than after halothane (48 min), (P < 0.01). Likewise, recovery was faster after sevoflurane anesthesia (P < 0.05). Agitation, but not pain, occurred more frequently after sevoflurane than after halothane (P < 0.05) and agitation was significantly more common in younger children. There was no difference in duration of hospital stay between day-care patients in the two groups.Conclusion: Early postanesthetic agitation and recovery was faster after mask anesthesia with sevoflurane than after halothane. There was a higher incidence of agitation in younger children, without correlation to pain. [ABSTRACT FROM AUTHOR]

Background: Adherence of pathogenic bacteria to host epithelial cells is thought to be the initial step in infection, while the presence of the commensal flora is an important host defence mechanism. Anything altering bacterial adherence to human epithelial cells may contribute to bacterial infections. The impact of anaesthesia on this first step to infection is not known. In this study the effect of halothane on bacterial adherence was investigated.Methods: Human epithelial cells (HEp-2) and two strains of Escherichia coli were exposed to halothane 2% for 2 h. Then HEp-2 cells were coincubated with bacteria for 3 h. Bacteria attached to the epithelial cells were evaluated by light microscopy.Results: Compared to the control, bacterial adherence was reduced by 37% to 56% with the different strains when HEp-2 cells were exposed to halothane. No significant difference was found when only bacteria were treated with halothane.Conclusion: Our results show that halothane reduces bacterial adherence to human epithelial cells in vitro. Reduced number or function of epithelial cell surface receptors may be responsible for the reduced adherence as no changes were observed when only the bacteria were exposed to halothane. [ABSTRACT FROM AUTHOR]

Background: The gap junction channel plays an important role in synchronous beating in the heart, and the reduction in the amount of gap junctional intercellular communication (GJIC) is thought to be the main arrhythmogenic factor in diseased heart. However, the effect of halothane on myocardial contraction in heart tissue with less GJIC is not well known. The purpose of the present study is to examine the direct effect of halothane on myocardium with poorly expressed GJIC.Methods: Ventricular myocytes were obtained from neonatal rats by enzymatic digestion with collagenase and then cultured for 3 or 7 d. We have previously reported that the number of gap junctions at 3 d is approximately 10% of that at 7 d (1). The myocytes were stabilized in serum-free medium, and the spontaneous beating rate and amplitude were measured by a fiberoptic sensor.Results: Heptanol (2 mM), an inhibitor of GJIC, abolished synchronized beating in myocytes cultured for 7 d. Halothane decreased the beating rate and amplitude in both groups of myocytes in a concentration-dependent manner (P < 0.05). Halothane at 1 and 2 MAC (adult rat MAC) decreased the beating rate more in myocytes cultured for 3 d than in myocytes cultured for 7 d (P < 0.05). Halothane reduced beating amplitude equally in both groups. Asynchronous contraction developed more frequently among myocytes cultured for 3 d than for those at 7 d.Conclusion: Halothane may block the GJIC channels, and when the number of these channels is reduced, exposure to halothane may cause asynchronous beating and decrease the beating rate. However, the halothane-induced decrease in amplitude is probably not due to blockade of GJIC because reducing the number of GJIC channels did not alter halothane's depressant effect. [ABSTRACT FROM AUTHOR]

Acute asthma is well known to provoke complications. We report the case of a patient who needed intubation and mechanical ventilation for acute asthma. Despite a treatment with corticosteroids, bronchodilators, neuromuscular blocking drugs and magnesium sulfate, the situation remained uncontrolled and as a last resort, halothane became necessary. The patient then developed an episode of malignant hyperthermia with fever at 40 degrees C and rhabdomyolysis. At this time, halothane could be stopped and all the symptoms disappeared without modifying the rest of the treatment. Eight days later, he presented with a neuroleptic malignant syndrome following an injection of droperidol. Temperature rose to 42 degrees C, associated with muscle rigidity, sweating, tachycardia and severe circulatory collapse. The use of dantrolene in association with a symptomatic treatment of the collapse led to a favourable outcome in. Unfortunately, in vitro contracture test could not be performed in this case. The links between malignant hyperthermia and neuroleptic malignant syndrome remain unclear. Although these two pathologies share the same physiopathology, symptomatology and treatment, they are clearly individualized. This case seems to be the first description of their occurrence in the same patient. [ABSTRACT FROM AUTHOR]

Background: Nociceptin is the endogenous agonist of the opioid receptor-like (ORL) 1 receptor (NOP), and both nociceptin and NOP are widely expressed in the brain and spinal cord, which are target organs of general anaesthetics. As nociceptin has been reported to be involved in modulating pain mechanisms and stress responses, it is possible that the activity of the nociceptin system affects the anaesthetic potency of general anaesthetics. To address this possibility, we investigated the minimum alveolar concentrations (MACs) of various volatile anaesthetics in nociceptin receptor knockout mice (NOP-/-) and wild-type mice (NOP+/+).Methods: We used male NOP-/- mice and NOP+/+ mice. MACs for halothane, isoflurane and sevoflurane were determined by the tail-clamp method.Results: MACs for halothane, isoflurane and sevoflurane in NOP-/- mice were 1.60 (SD 0.06), 1.68 (0.08) and 3.36 (0.07)%, respectively. In NOP+/+ mice, MACs for halothane, isoflurane and sevoflurane were 1.59 (SD 0.07), 1.72 (0.07) and 3.38 (0.09)%, respectively.Conclusion: MACs in NOP-/- mice did not significantly differ from those in NOP+/+ mice for halothane, isoflurane and sevoflurane. This result suggests that the nociceptin system does not affect the anaesthetic potency of volatile anaesthetics. [ABSTRACT FROM AUTHOR]

Background: Although no dose-response relationship for the health risks associated with the occupational exposure to inhaled anaesthetics exists, public health authorities recommend threshold values. The aim of the present study was to assess if and to what extent these threshold values are exceeded in an eastern European university hospital before and after measures had been taken to reduce occupational exposure.Methods: At nine workplaces occupational exposure of anaesthetists to nitrous oxide and halothane or isoflurane was measured by means of photoacoustic infrared spectrometry. The measurements were carried out in 1996 and were repeated in 1997 after the installation of active scavenging devices at five workplaces and an air-conditioning system at one workplace.Results: Occupational exposure to nitrous oxide and halothane or isoflurane was lower in 1997 compared to 1996. In 1997 most of the nitrous oxide values still exceeded the threshold value of 100 ppm, whereas most of the halothane and isoflurane values were already below the threshold values of 5 ppm and 10 ppm in 1996.Conclusion: The measures taken were effective in reducing waste gas exposure. Nevertheless, further efforts are necessary, especially for nitrous oxide, to reach western European standards. These efforts comprise structural measures such as active scavenging devices and air-conditioning systems at all workplaces, the use of total intravenous anaesthesia, low-flow anaesthesia and an appropriate working technique. [ABSTRACT FROM AUTHOR]

Inhalational induction is one of the recognized methods for the management of difficult airway. Halothane is the usual choice of agent for this purpose. The relatively new agent sevoflurane, which is the least irritant of all the available agents, is emerging as a choice of inhalational agent for both adult and pediatric populations. There are various reports for and against the use of sevoflurane for the management of difficult airway. We describe the use of sevoflurane for the management of difficult airway in four patients presenting with airway problems. [ABSTRACT FROM AUTHOR]

Background: In our clinical experience, children who are crying before anesthesia are more likely to show agitated behavior on emergence.Methods: One hundred and ten boys aged 3-6 years old (ASA 1) who underwent circumcision were studied. The children were assigned to one of two groups, depending on their attitude during induction: the anxious group and the calm group. Anesthesia was induced by inhalation of halothane in oxygen, and was maintained at 1% throughout surgery. For intra- and postoperative analgesia, caudal block with 0.5 ml/kg of 0.25% plain bupivacaine and topical infiltration with 1 to 2 ml of 1% lidocaine were provided for all patients. The incidence of delirium on emergence was compared between the groups.Results: We excluded 4 boys showing signs of incomplete pain relief. Twenty of 27 boys in the anxious group showed a significantly greater incidence of problematic behavior on emergence, compared to 5 of 79 in the calm group.Conclusion: The boys who were anxious before anesthesia showed a significantly greater incidence of problematic behavior on emergence from halothane anesthesia, compared with the boys who were calm before anesthesia. [ABSTRACT FROM AUTHOR]