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Die maligne Hyperthermie (MH) ist eine lebensbedrohliche hypermetabolische Krise. Sie kann im Verlauf einer Allgemeinanästhesie durch die Verwendung bestimmter Narkosegase auftreten. Zu den Symptomen zählen unter anderem eine generalisierte Muskelrigidität und ein rapider Anstieg der Körpertemperatur. Dies kann zu schweren Folgeschäden oder zum Tod führen. Ursächlich für die MH ist eine Störung der Kalziumhomöostase in den quergestreiften Skelettmuskelzellen. Eine zentrale Rolle spielt hierbei der Ryanodin-Rezeptor 1 (RyR1). Dieser Kanal ist für die myoplasmatische Freisetzung von intrazellulär gespeichertem Kalzium verantwortlich. In der folgenden Arbeit wurde die Änderung der Kalziumfreisetzung aus intrazellulären Speichern durch den Einfluss des Inhalationsanästhetikums Halothan an einem Mausmodell der MH näher untersucht. Besondere Aufmerksamkeit wurde dabei auf die Rolle einer Modulation des myoplasmatischen Membranpotentials gelegt.

In malignant hyperthermia (MH), volatile anesthetics induce hypermetabolism, lactic acidosis and rhabdomyolysis in predisposed patients. The authors hypothesized that intramuscular caffeine and halothane application would increase local lactate concentration in MH susceptible (MHS) individuals more than in non-susceptible (MHN) subjects without initiating the full MH syndrome.In 14 MHS, 12 MHN and 7 control individuals, microdialysis probes were placed in the rectus femoris muscle and perfused with Ringer's solution at 1 microl/min. After equilibration, 250 microl caffeine (80 mM) was injected through the first microdialysis probe, halothane 10 vol% dissolved in soybean oil was perfused through a second microdialysis probe and a third probe was used for control measurements. Dialysate samples were analyzed for lactate spectrophotometrically. Systemic hemodynamic and metabolic parameters were measured. Data are presented as median and quartiles.Intramuscular caffeine and halothane significantly increased local peak concentrations of lactate in MHS probands [5.0 mM (3.4-8.1 mM) and 3.7 mM (2.6-5.0 mM), respectively] compared to MHN [1.6 mM (1.3-2.0 mM) and 1.9 mM (1.6-2.0 mM)] or control individuals [2.1 mM (1.9-2.3 mM) and 2.0 mM (1.6-2.1 mM)]. This was accompanied by a higher serum creatine kinase level in the MHS group. Hemodynamic and metabolic parameters were normal in the investigated groups.Intramuscular caffeine and halothane application induces a temporary and abnormal increase of local lactate in MHS individuals. No serious systemic side effects occurred. This study presents evidence that metabolic monitoring with local stimulation by caffeine and halothane may allow a minimally invasive diagnosis of MH susceptibility.

Treatment of patients suffering from decompensated chronic pulmonary disease (COPD) not responding to pharmacological therapy is still a major challenge in intensive care medicine. Administration of volatile anaesthetics may be a therapy of last resort in these cases. We report on a 65-year-old woman suffering from exacerbated COPD, who could not be sufficiently ventilated despite comprehensive pharmacological therapy. In order to administer a volatile anaesthetic in the ICU, we employed the "Anaesthetic Conserving Device" (AnaConDa) consisting of a vaporizer chamber embedded in a charcoal filter system. With this device, every standard intensive care ventilator can be used to deliver volatile anaesthetics in a safe and economic manner. The AnaConDa converts the open breathing system of the intensive care ventilator into a de facto half-closed system. The very low pulmonary compliance of the patient increased dramatically after administration of 0.75 vol% halothane for 48 h (27 vs. 150 ml/mbar). Elimination of CO(2) was improved and weaning from controlled ventilation was achieved. After surgical removal of a pulmonary abscess and a total of 78 days of intensive care therapy, the patient was discharged in good health.

We report on a 25-year old ASA physical status I patient, who developed within 20 minutes a full-blown malignant hyperthermia (MH) in the context of a living donor liver transplantation after 180 minutes of uneventful anaesthesia. The only trigger substance applied was Sevoflurane. The patient had already received a short, uneventful anaesthesia with Isoflurane a couple of years ago. In the context of the special constellation an initial dose of Dantrolene of 10 mg/kg body weight was administered. The patient was stabilised within 30 minutes, and the enzyme levels remained low compared with other case reports. The post-operative in vitro caffeine halothane contracture testing confirmed that son and mother were susceptible to MH, contracture testing in the father was negative. All known triggers may cause life-threatening MH crisis - even after hours and after inconspicuous multiple exposures to known trigger substances. Therefore all trigger substances must be avoided in all patients susceptible to MH.

Volatile anesthetics used in daily clinical routine, are associated with a rare but life-threatening disease, malignant hyperthermia. To date it is well known that, with the exception of xenon and nitrous oxide, all volatile anesthetics have the potential to trigger calcium (Ca(2+)) release from the sarcoplasmic reticulum, thereby influencing the Ca(2+) homeostasis in muscle fibers. The effects of volatile anesthetics have been previously studied by recording Ca(2+)-activated force transients in muscle fibers and by quantifying the effects on isolated intracellular Ca(2+)-release channels (ryanodin receptors). The use of high resolution fluorescence microscopy methods in combination with spatio-temporal mathematical models allows the effects of volatile anesthetics on functional clusters of ryanodin receptors in mammalian skeletal muscle fibers to be studied in situ for the first time.Thus, the analysis of cellular Ca(2+)-activated force production and single channel properties in conjunction with mathematical models allows the quantification of the effects of volatile anesthetics on Ca(2+)-release in the natural physiological environment on the basis of the underlying molecular architecture. In addition to the basic understanding of alterations in the Ca(2+) homeostasis induced by volatile anesthetics in muscle and nerve cells, the results are also of direct clinical importance for the understanding of the pathogenesis of malignant hyperthermia,where ryanodin receptor mutations are currently thought to result in an increased Ca(2+) release under the influence of volatile anesthetics.

Halothane causes impairment of cerebrovascular reactivity and autoregulation. We used transcranial Doppler sonography (TCD) to investigate the reaction patterns of cerebral blood flow velocities (CBFV) during a standardized orthostatic maneuver after premedication and during halothane anesthesia in infants. After premedication orthostasis led to no significant changes in CBFV. During halothane anesthesia CBFV was significantly higher than after premedication, and orthostasis induced a significant decrease in CBFV compared to values obtained in horizontal position. Heart rate and mean blood pressure were significantly lower than before medication during halothane anesthesia. The observed changes in CBFV during halothane anesthesia represent a characteristic pattern of impaired cerebral autoregulation. The changes in CBFV and heart rate demonstrate that neither systemic nor cerebral hemodynamics compensate for hydrostatic inducement during halothane anesthesia. The tilting test is a useful tool for determining cerebral autoregulation capacity in infants.

In the postoperative period after coronary artery bypass graft surgery, the physician's enhanced attention should be focused on the incidence of myocardial ischaemia. The increased stress in the awakening patient as well as the return of autonomous reflexes can be the cause of imbalances in myocardial oxygen supply and uptake. Therefore, a probable influence of the pharmacologic profile of the intraoperatively applied anaesthetics on the incidence of postoperative myocardial ischaemia is of importance for adapting therapy on ICU to minimize any ischaemic risk. After approval by the ethics committee, a prospective randomized study was performed in 40 male patients who underwent coronary artery bypass graft surgery. The aim of the study was to compare balanced anaesthetic techniques performed with fentanyl and halothane, isoflurane and enflurane, respectively, with total intravenous anaesthesia performed with fentanyl and midazolam. An index to classify detection of ischaemia into three categories (ischaemia, probable ischaemia, no ischaemia) was established, based on measurements of myocardial lactate extraction and ST-segment analysis. Simultaneously, measurements of haemodynamic parameters and serum concentrations of catecholamines and intraoperatively applied anaesthetics were taken. In 8% of all measurements (30% of all patients) ischaemia was detected in the observation period and in 37% of all measurements (72.5% of all patients) probable ischaemia was detected. No significant difference was found concerning the incidence of myocardial ischaemia between all groups. The results of this investigation indicate that the application of inhalational anaesthetics for maintaining anaesthesia in coronary artery bypass graft surgery does not increase the risk of postoperative myocardial ischaemia.

The unwanted side effects of muscle relaxants used for anaesthesia in the newborn and infants resulted in a search for alternatives to atraumatic intubation (IN). The study was aimed to investigate conditions of intubation, time of intubation as well as changes in systolic, mean and diastolic blood pressure (RRs/RRm/RRd) and heart rate (HR) under the use of propofol (P) after narcosis induction by mask.The study was approved by the local ethics committee. The data was analysed from 100 infants aged between 4 days and 56 weeks (weight 2110-9230 g) in the ASA I and II groups (Group [Gr] A and B both with 50 patients). In both groups induction was performed inhalationally with halothane (1.5-2.0 vol%) and pure oxygen. After that propofol for intubation was applied in a dose of 2 mg/kg i.v. In Gr A blood pressure and heart rate were registered at three measuring points (MP): MP 1 = before P administration, MP 2 = after P, MP 3 = following intubation; in Gr B at MP 1 and MP 3. Additionally in Gr B the intubation time was recorded in seconds (t1 = time after P administration to beginning of IN, t2 = time after P administration to the end of the IN, t3 = t2-t1). In both groups the conditions of intubation were assessed (score 1--excellent, 2--good, 3--bad, 4--impossible intubation).The means of RRs/RRm/RRd/HR varied in Gr A at MP 2 by -11.20*/-9.18*/-8.58*/-3.52 mmHg/bpm and at MP 3 by -2.74/-2.26/-2.04/+5.46 mmHg/bpm in comparison to MP 1 (p0.05 = significant*). Compared to MP 1 in Gr B the mean values of RRs/RRm/RRd/HR varied at MP 3 by -0.89/+0.50/-0.80/+4.20* mmHg/bpm. T1 (mean, SD) was 10.88 +/- 3.52 seconds (s), t2 26.22 +/- 6.12 s, and t3 was therefore 15.78 +/- 6.28 s. Conditions of intubation were found to be excellent or good in both groups (Gr A and B [100 patients]: score 1 = 95x = 95%, score 2 = 5x = 5%).In the observation period, changes in heart rate stayed in the range of reference. In our opinion the excellent and good conditions for intubation, as well as the ultrashort drug-onset and intubation time demonstrate the good characteristics afforded by propofol to perform intubation in infancy.

Inhalational anaesthesia is the most common anaesthesia technique in paediatric anaesthesia worldwide. Up to now the standard anaesthetic used is halothane. Because halothane is tolerated in the upper airways without side effects it is well suited for the inhalational induction of anaesthesia. However, halothane exerts side effects on the hepatic and the cardiovascular system. This review focuses on the replacement of halothane by sevoflurane in paediatric anaesthesia. Apart from its favorable pharmacological properties sevoflurane is also superior because of economical considerations. The following conclusions are drawn: (1) Halothane and sevoflurane do not cause irritations of the airways and are thus suitable for an inhalational induction. Sevoflurane should be administered in oxygen/nitrous oxide during induction of anaesthesia to reduce excitation. (2) The MAC values of sevoflurane are age dependent. In contrast to adult patients the MAC values of sevoflurane are only decreased by 20 to 25% in paediatric patients. The end-tidal concentration of sevoflurane necessary for intubation or insertion of a laryngeal mask is 2 to 4 Vol.%. (3) The blood/gas partition coefficient of sevoflurane is low, resulting in shorter induction times with sevoflurane compared to halothane. The so called priming technique with 8 Vol.% of sevoflurane results in shorter induction times. Consequently, times to recovery and psycho-motor functions are favourable for sevoflurane compared to halothane in paediatric patients. However, shorter recovery times lead to earlier perception of postoperative pain, requiring adequate pain management. (4) The hemodynamic stability after administration of sevoflurane is favourable to that after halothane in paediatric patients, leading to significantly less bradycardia. (5) In paediatric patients no negative effects on kidney function have been observed after administration of sevoflurane. There is no scientific basis for organotoxic effects, thus sevoflurane is suitable for low-flow and minimal-flow anaesthesia. (6) The duration of the action of muscle relaxants is increased to a greater extent in presence of sevoflurane compared to halothane. Consequently, the total dose of muscle relaxants can be reduced using sevoflurane. (7) Similar to the established inhalational anaesthetics sevoflurane triggers malignant hyperthermia (MH) and must not be used in patients in which MH is suspected or in which a predisposition for MH is known.

1969 Sevofluran was synthesized and in December 1995 licensed for clinical use in Germany. The low blood/gas partition coefficient is responsible for the fast uptake and elimination of sevoflurane. Sevoflurane does not irritate the airway. In human medicine no side effect of liver- and kidney function have been seen after sevofluran anaesthesia. There is low cardiovascular and respiratory depression caused by sevoflurane. In this study the use of sevoflurane in dogs should be tested and compared with isoflurane and halothane anaesthesia. All dogs were premedicated with /-methadon and diazepam. No significant depression of the cardiovascular system was seen. Neither kidney-nor hepatotoxic side effects could be found after sevoflurane, isoflurane and halothane anaesthesia. After sevoflurane anaesthesia the dogs woke up quietly and without any excitation and were able to stand on average ten minutes earlier after sevoflurane anaesthesia than after isoflurane and 85 minutes earlier than after halothane anaesthesia.

The volatile agent sevoflurane enables a rapid emergence from anaesthesia. The aim of this study was to investigate the possibility of increasing turnover in pediatric anaesthetic cases by use of sevoflurane in comparison with halothane. Often short cases or day cases need rapid turnover.The pediatric patients aged 4-14 years (ASA I) presenting for elective ophthalmic surgery were randomised to either the halothane or the sevoflurane group. Standard monitoring was applied to all patients, in addition the pEEG was used to determine comparable anaesthetic depth. Sevoflurane or halothane were titrated to a SEF 90 of 8-12 Hz. Management of the airway was done with the RLMA (reinforced laryngeal mask). All patients were under controlled ventilation. At the end of surgery and anaesthesia 3 time intervals were measured: phase I) end of anaesthetic application--start of spontaneous respiration; phase II) start of spontaneous respiration--removal of RLMA. The SEF 90 interval was also assessed.18 cases were included (halo n = 8/sevo n = 10, no significant differences concerning weight, age, anaesthesia time). There is a significant advantage for the Sevoflurane group in phase II of 6.8 minutes. No differences were seen in phase I and SEF 90 interval.Sevoflurane offers the potential for shortening turnover in pediatric anaesthesia.

Halothane anesthesia is frequently used for pediatric bronchoscopy. A disadvantage of the equipment used, a rigid bronchoscope together with inhalation anesthesia is the contamination of the working environment. The aim of this study was to determine the exposure of anesthetist and endoscopist during pediatric bronchoscopy under halothane anesthesia in a worst-case working environment and to compare these measurements with the currently valid international threshold values. Ten children (ASA I-III) scheduled for diagnostic bronchoscopy were included in the study. After induction with thiopentone and relaxation with atracurium all children were intubated with a rigid bronchoscope and manually ventilated through a bypass of the bronchoscope. Anesthesia was maintained by means halothane (0.5-2.0 vol%) in 100% oxygen with a flow of 10 l/min. The investigation was done in an operating room without air conditioning and scavenging system. Trace concentrations were measured every 2 minutes in the breathing zones of the anesthetist and the endoscopist by means of a highly sensitive direct reading instrument. Lower detection limit was 0.02 ppm. The mean age (+/- SD) of the children was 29.9 +/- 15.9 months (range: 4 weeks-48 months). Ventilation and oxygenation were stable throughout the bronchoscopic procedure. Mean exposure (+/- SEM) to halothane was 57.7 +/- 18.9 ppm for the anesthetist and 96.3 +/- 22.9 ppm for the endoscopist. The difference was statistically significant (ANOVA, P0.05). All international threshold values (2-50 ppm) were exceeded by far. Peak concentrations higher than 200 ppm halothane could be detected several times. The main result of the present study is that under the given situation in the operating room with insufficient room ventilation and no scavenging system halothane anesthesia for rigid bronchoscopy in children results in an occupational exposure that is higher than all known health regulation guidelines. Therefore, in case of insufficient working conditions total intravenous anesthesia might be a better alternative also in very small infants.

In 35 ASA group I and II patients we investigated the influence of haemodynamic changes induced by increasing concentrations of halothane (from 0.0 to 0.6% halothane in 70% N20) on parameters of transesophageal echocardiography (TEE). Measurements by TEE were taken in manual and automatic boundary detection mode. In manual mode the left ventricular endsystolic area (ESA) increased significantly (+16.3%) and the fractional area change (FAC) decreased significantly (-14.9%). There was no significant change of left ventricular end diastolic area (EDA). In the automatic mode there was a significant increase of ESA and EDA (+13.8%; +6.0%) and a significant decrease of FAC (-10.9%). Peak ejection rate (PER) and peak filling rate (PFR) which were also assessed in automated mode decreased significantly (-10.0%; -5.7%) under halothane. No change occurred with manually determined left ventricular endsystolic wall stress (LVEWS). The endsystolic quotient decreased significantly both in manual and automated mode during halothane (-28.3%; -29.9%). No significant difference existed between TEE measurements under apnoea versus under controlled ventilation (except for EDA in automated mode). We conclude that there is no need for apnoea conditions for TEE measurements. In conclusion, TEE proves a useful monitoring system in anesthesia which enables the investigator to assess the negative inotropic effect of halothane. Problems in its practical usage are due to the wide variation of TEE measurements.

New anaesthetic agents are being continuously developed to find the ideal agent. The most commonly used inhaled anaesthetic in adults is isoflurane and in children halothane. The need for, and the value of the new agents desflurane and sevoflurane depend on a comparison of the properties of a theoretically ideal agent with those of isoflurane, halothane and the new agents. Therefore, the following topics are discussed in the overview: pharmacokinetic properties, recovery parameters, mask induction in adults, paediatric anaesthesia, metabolism, stability in carbon dioxide absorbents and cardiovascular effects. Desflurane and sevoflurane may be considered a step toward the ideal inhalational agents. Both possess the advantage of rapid recovery from surgical anesthesia. Desflurane has a major advantage over sevoflurane: it is not biotransformed nor does it interact with carbon dioxide absorbents. However, desflurane is associated with troublesome cardiovascular stimulation involving tachycardia and both pulmonary and systemic hypertension. Sevoflurane appears to be advantageous for three reasons: firstly, because of its pleasant odour and consequent suitability for induction by inhalation, particularly in paediatric anaesthesia; secondly, it can be used with currently employed vaporizers, and thirdly, surgical demands can be met by lower doses, because its potency is higher.

The purpose of this study was to show the behaviour of the plasma level of catecholamines in stress-susceptible pigs during an acute stress and to gain new insights in the role of catecholamines in the initiation of malignant hyperthermia. Therefore, a halothane challenge test was performed in stress-susceptible growing pigs, and the changes of haematocrit, hormones and metabolites were monitored during the handling before the test, during halothane exposure and thereafter. Already in connection with the handling before the test, haematocrit values and plasma levels of epinephrine, norepinephrine, glucose, lactate and potassium increased significantly. However, the plasma concentration of cortisol and free glycerol increased gradually and the level of nonesterified fatty acids did not show any changes. While the levels of catecholamines and potassium decreased already during halothane exposure, haematocrit values and concentrations of glucose and lactate continued to increase. The present results indicate that the catecholamines are not involved in the initiation of malignant hyperthermia.

In the presence of completely dry soda lime volatile anaesthetics will decompose to carbon monoxide (CO). In an in vitro study, the absorbent (soda lime, ICI) was dried with a constant gas flow of 11/min oxygen for 120 h. The weight loss during the drying was 17.1%. Two vol% of halothane, enflurane or isoflurane in oxygen was administered with a constant flow of 0.51/min oxygen through the completely dry absorbent. Concentrations of gases were measured before and after the absorbent using mass spectrometry (MGA 1100, Perkin-Elmer) and an electrochemical NO monitor (Mini PAC CO, Dräger). The temperature inside the soda lime was monitored continuously. Shortly after adding the anaesthetic to the oxygen passing through the absorbent, carbon monoxide appeared in the outlet of the soda lime container. The measured peak concentrations varied around 450 ppm (halothane), 3500 ppm (enflurane) and 3800 ppm (isoflurane). The temperature inside the absorbent rose from the ambient temperature (19.8 degrees C) to a maximum of 52.1 degrees C during CO production and decreased when the CO production lowered after approximately 1 h (all anaesthetics). During CO production no measurable concentration of halothane left the absorber. After passing through the absorbent the concentrations of isoflurane and enflurane were slightly lower than the corresponding concentrations in the fresh gas measured before absorption.

Objective of this investigation was to compare the effects of the new inhalation agent desflurane with equipotent doses of isoflurane and halothane on hepatic blood flow (tHBF).36 Patients scheduled for elective aortocoronary bypass grafting were enrolled to the study. tHBF was assessed by plasma clearance and hepatic extraction of indocyanine green, and standard haemodynamic parameters were measured by thermodilution technique. The measurements were performed awake and after intubation at equilibration of 1 MAC. All measurements were terminated before skin incision.We found a significant decrease of tHBF in all patients regardless of the inhalation agent used (H 918 ml/min +/- 107 to 625 ml/min +/- 181, I 930 ml/min +/- 195 to 637 ml/min +/- 137, D 940 ml/min +/- 129 to 677 ml/min +/- 122). The tHBF in relation to cardiac output also decreased significantly (H 17% +/- 5 to 14% +/- 3, I 16% +/- 3 to 14% +/- 5, D 20% +/- 5 to 18% +/- 6). No difference was seen between the groups according to tHBF and haemodynamics.The results of this study suggest that all inhalation agents included in the study significantly decreased tHBF during anaesthesia with the concentration of 1 MAC.

We report on a young patient with a positive family history for malignant hyperthermia (MH), who was diagnosed as susceptible to MH in our malignant hyperthermia laboratory by the in vitro-contracture test. Prior to the investigation of MH-susceptibility, the patient had been on medication with moclobemide, a monoamine oxidase (MAO) inhibitor, over a period of 13 months for treatment of a hyperactivity disorder. During the therapy with moclobemide no signs of relevant side effects were observed. However, some authors regard MAO-inhibitors as MH-triggering agents. The risk of MH-patients due to the therapy with MAO-inhibitors and the association between MH and the neuroleptic malignant syndrome is discussed in this case report.

Mivacurium is a new non-depolarising muscle relaxant with a relatively rapid onset and short duration of action. In children, intravenous injection of 0.2 mg/kg produces satisfactory relaxation. Because inhalational anaesthetics have been found to enhance the potency of muscle relaxants we determined if onset or recovery times following mivacurium are influenced by inhalation of halothane (HAL), enflurane (ENF) or isoflurane (ISO).After intramuscular induction, 36 surgical children (2-6 years, ASA I) were randomly assigned to inhale either HAL (n = 12); ENF (n = 12) or ISO (n = 12). The train-of four (TOF) response was determined electromyographically (Relaxograph, Datex) at 20-second time intervals. Following ten minutes of inhalation of either HAL, ENF or ISO (0,8; 1,2; 1,0 vol% respectively) in N2 O/O2 (2:1), 0.2 mg/kg of mivacurium was injected intravenously. Patients were intubated at maximal T1-suppression and the intubating conditions were judged according to a graded score. Upon recovery of T1 = 25%, six patients in each group were antagonised with 30 micrograms/kg of neostigmine and 15 micrograms/kg of atropine; the recovery indices were compared with those from non-antagonised patients. Differences between groups were tested with multifactorial analysis of variance (p0.05).Intubating conditions were graded as "excellent" or "good" in all patients but one who showed moderate breath holding following the tube passage. Onset times of mivacurium were not different between patients receiving HAL: 2.4 min +/- 0.52 (+/ SD); ENF: 2.4 min +/- 0.55 or ISO: 2.6 min +/- 0.68. Time to T1 = 25% was 7.6 min +/- 2.91 (HAL); 7.9 min +/- 1.55 (ENF) and 8.6 min +/- 2.30 (ISO). Recovery indices were not significantly different between groups. Total duration of action in non-antagonised patients was 13.0 min +/- 3.32 (HAL); 14.3 min +/- 4.01 (ENF) and 19.6 min +/- 5.17 (ISO), whereas antagonised duration of action was 13.4 min +/- 5.11 (HAL); 13.3 min +/- 1.97 (ENF) and 15.6 min +/- 4.25 (ISO). The shorter total duration of action in patients receiving neostigmine (average 0.5-2 minutes) was statistically insignificant.Following injection of 0.2 mg/kg of mivacurium, no clinically relevant differences in onset or recovery times were found between children receiving halothane, enflurane or isoflurane. No differences in heart rate or blood pressure were found between groups. Compared to previous investigations with mivacurium, we noted a 30-60% longer mean onset time and a 30% shorter mean spontaneous recovery time. This may be explained by the lower mean age of our patients, which correlates with a relatively higher volume of distribution, resulting in lower plasma concentrations if the dose is calculated per kilogramme body weight. The reduction of the mean recovery time by 2 minutes following neostigmine injection seems to be clinically irrelevant. Similar to adult, a twofold ED95 produces satisfactory surgical muscle relaxation in children receiving mivacurium. Thus, its onset time is comparable to that of vecuronium or atracurium. The shorter duration of action offering a tighter control over relaxation may be of clinical advantage in this age group.

Due to its low blood:gas partition coefficient (0.69) and its neutral odor, sevoflurane (S) is suitable for inhalational induction of anaesthesia. At the moment halothane (H) is preferentially used for this purpose due to its non-irritating odor and the smoothness of anaesthetic action. However, experience is limited with the use of S in children, and concern exists about potential renal toxicity of its metabolite, i.e. fluoride. Therefore, we compared S and H in an open, randomized phase III trial.With approval of the ethics committee and written informed parental consent, 40 children (age 1-10, mean 5.3 years, ASA class I and II) had anaesthesia induced without premedication (fresh gas flow 6 l/min, N2O/O2 = 65/35). Concentration of volatile anaesthetics was increased every 3-5 breaths (S: 0.8...3.2 vol%, H: 0.4...1.6 Vol%). The ciliary reflex was tested until it disappeared. Airway reflexes and excitation were quantified using a score. Upon venipuncture, relaxation and intubation, anaesthesia was maintained with S (Fi: 2.4 vol%) or H (Fi: 1.2 vol%) in N2O/O2 (3 l/min, etCO2 35-38 mm HG). Alfentanil was supplemented in repeated doses of 20 micrograms/kg. ECG, NIBP, SpO2, Fi and Fet of CO2 and volatile anaesthetics were continuously recorded. At the end of surgery anaesthetics were terminated abruptly and fresh gas flow was increased to 6 l/min O2. Time to the first purposeful movement was registered. Serum fluoride levels were determined immediately after venipuncture, at the end of surgery and 70 min later. Time to possible discharge from the PACU was quantified using a modified Aldrete score. Data were analysed with descriptive methods, Student's t-test or non-parametric tests as appropriate.Groups did not differ with respect to age, weight, sex, or type of surgery. Total dose of anaesthetics was 1.60 MACxh for S and 1.77 MACxh for H (p = 0.68). Table 6 shows the essential data. Mean arterial blood pressures and heart rate remained within +/- 20% of age-related normal values (Table 7). Mean serum fluoride level was 23.1 +/- 1.2 mumol/l at the end of surgery and decreased to 18.6 +/- 0.970 min later (Fig. 3).Sevoflurane is an alternative to halothane in pediatric inhalational anaesthesia, with a comparable, low incidence of airway irritation and smoothness of induction. Because of the significantly faster induction and recovery it seems superior to halothane. With the fluoride levels measured, an impairment of renal function is unlikely.

To assess the occupational exposure of the anaesthetist to anaesthetic gases, a total of 1 German and 25 Swiss hospitals were investigated. A BrüelKjaer Type 1302 multi-gas monitor was used to measure concentrations of nitrous oxide and halogenated anaesthetic agents in the anaesthetist's breathing zone. Measurements were performed during 114 general anaesthetic, 55 of which were in patients under 11 years of age. In these 55 patients, the influence of various factors on the exposure (time-weighted average concentrations) was estimated by comparing different data groups. The efficiency of the applied scavenging equipment was examined by surveying the exhalation valve with a leak detector (type TIF 5600, TIF Instruments, Miami).Sessions with patients under 11 years of age revealed much higher anaesthetic gas exposures compared to older patients. The concentrations of nitrous oxide were on average threefold (Fig. 1), those of the halogenated anaesthetics fivefold higher (Fig. 2) for the younger patients. In 11- to 16-year-old patients the exposure level was the same as in adult patients. The measurements showed a reduction of 85% in exposure if an efficient scavenging system (i.e., no waste gas discharge to room air through the exhalation valve) or lower fresh gas flow were used (Fig. 4); 42% of the inspected scavengers were inefficient, and reduced the exposure on average by only 30%. In operating theatres with a ventilation rate of at least ten air changes per h, the measured concentrations of anaesthetic gases in the inhalation zone of the anaesthetists were reduced more than 50% compared to poorly ventilated rooms (Figs. 4 and 5). The use of tracheal intubation or laryngeal mask airway (LMA) anaesthesia resulted in a reduction of 80% in exposure compared to standard face masks if efficient scavenging was used. The exposures during sessions with inefficiently scavenged Bain coaxial systems or unscavenged semi-open delivery systems of the Jackson-Rees type were tenfold higher than with scavenged rebreathing circuit systems (Fig. 6). During anaesthesia with IV or double-mask induction, the average levels of inhalation anaesthetics were reduced by about 80% compared to inhalational induction with standard masks (Fig. 7). The anaesthetist's working technique is a very important factor that strongly influences the concentrations. Poor work practices, like lifting off the face mask with anaesthetic gas flow turned on, increased the exposure of the anaesthetist and other operating room personnel drastically, even if the other conditions (scavenger and room ventilation) were good.The exposure levels of anaesthetic gases are generally higher during anaesthesia in children up to 10 years of age than in older patients. Nevertheless, the measurements showed that exposure during paediatric anaesthesia can be kept below the recommended limit (8-h TWA in Switzerland) of 100 ppm nitrous oxide and 5 ppm halothane or 10 ppm enflurane or isoflurane. Causes of high exposures were particularly high fresh gas flows often applied without scavenging or together with inefficient scavenging devices and the high part of mask anaesthesia and inhalation induction with a loosely held mask. To achieve an effective reduction of occupational exposure, well-adjusted and maintained scavenging systems and low-leakage work practices are of primary importance. As leakage can never be completely avoided, a ventilation rate of at least ten air changes per h should be maintained in operating rooms and rooms where anaesthesia is induced to keep down concentrations of waste anaesthetic gases. High exposure during mask anaesthesia and inhalation induction can be prevented by further measures. Using a LMA instead of a standard mask reduces the exposure to the same level as endotracheal intubation.

The present experimental study on 16 acutely instrumented dogs was designed to determine the haemo- and cardiodynamic changes after an intravenous infusion of nifedipine during halothane or isoflurane anaesthesia.General anaesthesia was induced with ketamine (10 mg/kg) and fentanyl (0.02 mg/kg) and maintained with fentanyl (0.3 micrograms/kg/min), 3:1 N2O/O2 inhalation mixture, and pancuronium (300 micrograms/kg/h). A left thoracotomy was performed and a needle force probe was placed in the left ventricular wall to measure myocardial force of contraction. A Widney gauge was placed around the left ventricle to measure left ventricular circumference changes. The animals were also monitored with left ventricular tip manometers, pulmonary arterial thermodilution catheters, and femoral arterial and venous catheters. Three hours after instrumentation baseline haemodynamic measurements were performed and repeated 30 min after either halothane 0.8 vol.% (n = 8) or isoflurane 1.5 vol.% (n = 8). Then nifedipine (10 micrograms/kg i.v.) was administered and haemodynamic measurements were repeated.Both volatile anaesthetic agents caused a decrease in MAP, CO, LVP, LVFS, and dP/dtmax. Heart rate, CVP, PAOP, and the diastolic diameter of the heart did not change with halothane and isoflurane. Isoflurane led to a decrease of SVR that was not seen with the administration of halothane. Nifedipine during halothane anaesthesia caused a further decrease in MAP, SVR, LVP, dP/dtmax, and LVFS compared to the already reduced values with halothane alone. However, SV did not decrease any further. If nifedipine was added to isoflurane a further decrease in CO and SV was observed despite a constant SVR.Halothane, isoflurane and nifedipine are cardiac depressant drugs. Isoflurane induces vasodilation and appears to be less cardiodepressant than halothane in the clinical situation. However, if nifedipine is added, the vasodilation caused by nifedipine offsets its own negative inotropic effect and in parts the cardiac depression of halothane. Combined with isoflurane the vasodilatory effect of nifedipine is insignificant and the negative inotropic effects of both drugs are additive resulting in a profound decrease in SV and CO.

The effects of halothane on the cerebral circulation were studied in 23 children during general anaesthesia. Blood flow velocity in one middle cerebral artery was recorded continuously by transcranial Doppler sonography. Furthermore arterial blood pressure, pulse rate, endtidal CO2partial pressure and endtidal halothane concentration were recorded. Mean flow velocities/mean arterial blood pressures were 79 cm x s-1/65 mmHg; 86 cm x s-1/61 mmHg; 78 cm x s-1/54 mmHg and 67 cm x s-1/48 mmHg with 1; 1.5; 2 and 2.5 per cent endtidal halothane concentrations, respectively. Endtidal CO2-partial pressure and pulse rate remained constant throughout the study. The higher cerebral blood flow velocities seen with 1.5 per cent halothane compared with 1 per cent can be explained by an increase in cerebral blood flow. The lower cerebral blood flow velocities and arterial blood pressure with 2.5 per cent halothane compared with 1.5 per cent indicate impaired cerebral autoregulation. However, cerebral blood flow appeared to be sufficient even with low arterial blood pressures.

When working with the anaesthetics vaporizers/respirators of the type Siemens Servo 900 C/D we found differences between the values adjusted at the instrument and those measured by the anaesthetic gas monitor (Sirecust 734 G). Control measurements yielded differences of inspiratory concentrations of halothane and isoflurane that were in excess by up to 80%. We found that the reason for this was the absence of reducing valves at the respirator that would reduce the static pressure of central gas supply from 5.3-5.5 bar to the values of not more than 4.0 bar that are permissible for the vaporizer. It is pointed out that the operation of respirators of this type is safe only provided the prescribed gas supply pressures are observed, if necessary with the help of the appropriate reducing valves, to ensure accurate dosage of volatile anaesthetics.

Volatile anesthetics are suspected to cause various health risks even in subnarcotic concentrations (hepatotoxicity, mutagenicity, teratogenicity). Yet only for halothane a limit (MAK-value = 5 ppm) has been established for the entire FRG. In addition, in 1991 Hamburg and Schleswig-Holstein defined preliminary limits for isoflurane, enflurane and nitrous oxide. We analysed the pollution of operating-room air by narcotic gases in 20 hospitals of Niedersachsen. In several cases limits have been exceeded evidently. Reasons for high concentrations were: insufficient room ventilation, defective air-conditioning plants, technical defects (leakage) and high gas emission due to special techniques in anesthesia (bronchoscopy). In order to take care of personnel-health air concentration of anesthetic gases should be kept as low as possible by the help of sufficient room ventilation avoiding unnecessary emissions.

Early mental and psychomotor recovery was studied in 67 patients undergoing colorectal surgery under continuous epidural anaesthesia and light general anaesthesia using propofol, halothane, and midazolam/fentanyl. The study was approved by the local ethics committee. All patients received epidural anaesthesia with 0.25% bupivacaine and were then randomly allocated to one of three groups. In group I (halothane), light general anaesthesia was induced with thiopental 3-5 mg/kg and maintained with halothane. The propofol group (II) received 2 mg/kg for induction and a mean continuous infusion of 1.7 mg/kg.h. In group III (Mi/Fe), midazolam and fentanyl were used for induction and maintenance. All patients were intubated, received non-depolarising muscle relaxants, and were manually ventilated with nitrous oxide-oxygen (2:1.2). For postoperative analgesia, 0.05 mg/kg morphine was administrated epidurally 30 min before the end of the operation; 30, 60, 90, and 120 min after arriving in the recovery room, vigilance was assessed using a modified Steward score, the Trieger test, the ability to recall a column of numbers (KAI test), and symbol counting (CI test). Heart rate, blood pressure, arterial oxygen saturation, and blood gases were recorded. RESULTS. The three groups were comparable with regard to age, sex, ASA classification, and duration of anaesthesia and operation (Table 3). There was no difference between the groups in performance of the recovery tests (Figs. 2-5), blood pressure, heart rate, arterial blood gas analysis (Fig. 6), or oxygen saturation. Comparing pre- and postoperative values, we found severe psychomotor and mental impairment in all groups. pCO2 was slightly elevated in all groups, but only 3 patients in the propofol group and 6 in the midazolam/fentanyl group developed hypercapnia above 50 mm Hg. Patients receiving propofol or midazolam/fentanyl had significantly less postoperative nausea and vomiting than those receiving halothane (Table 5). CONCLUSION. It is concluded that propofol offers no advantage over halothane or midazolam/fentanyl where early postoperative recovery is concerned. Intraoperatively, all three techniques provided good anaesthesia. Propofol and midazolam/fentanyl caused less postoperative nausea and vomiting than halothane anaesthesia.

The halothane test was performed under different conditions in 10 halothane-sensitive growing pigs (Landrace, line 01). Haematological and metabolic changes in blood were monitored during the handling of the pigs before the test, during the exposure to halothane and thereafter. Already in connection with the catching and fixation of the pigs, the levels of haemoglobin in blood, and of glucose, lactate and potassium in plasma increased significantly. However, the concentration of glycerol was not raised before the occurrence of the malignant hyperthermia. While the level of potassium decreased already from the beginning of the halothane exposure until the development of symptoms, the values of haemoglobin, glucose and lactate continued to increased. The level of the free fatty acids did not show any changes during the experimental period. An infusion of phentolamine reduced the increase of haemoglobin and potassium and an infusion of propranolol reduced the increase of haemoglobin and glycerol significantly, without any effect on the result of the halothane test. By an anaesthesia, starting 30 minutes before the exposure to halothane, the development of the typical halothane reaction was obviated for at least 10 minutes. Observed metabolic changes during a simultaneous epinephrine administration were exclusively due to its adrenergic effects.

We investigated the pharmacodynamic effects of the phosphodiesterae inhibitor enoximone in the presence of halothane and isoflurane in 20 patients, ASA class III, aged 45-75 years, undergoing coronary artery bypass grafting. The study was approved by the local Medical Ethics Committee and patients' informed written consent was obtained.After induction of anaesthesia (midazolam, fentanyl, etomidate and pancuronium) all patients received either halothane 1 MAC (group I, n = 10) or isoflurane 1 MAC (group II, n = 10), followed 20 min later by enoximone 0.5 mg/kg. Haemodynamic variables were measured and blood samples (arterial, mixed venous) were obtained before the administration of the volatile anaesthetics (control, t0), immediately (t1) and 5 (t2) min after steady state conditions with halothane or isoflurane, as verified by the end-expiratory concentration and 5 (t3) and 10 (t4) min after the injection of enoximone. Heart rate (HR), mean arterial pressure (MAP), mean pulmonary artery pressure, pulmonary capillary wedge pressure and right atrial pressure were recorded. Cardiac (CI) and stroke volume indices, systemic (SVR) and pulmonary vascular resistance, oxygen availability (AO2) oxygen consumption and oxygen extraction rate were calculated using standard formulae.In both groups HR remained essentially unchanged throughout the investigation period. MAP decreased significantly in both groups under steady state conditions with the volatile anaesthetics (group I: 19%; group II: 30%) but remained unchanged after subsequent injection of enoximone. After administration of halothane SVR remained essentially unchanged, whereas isoflurane decreased SVR significantly by 20%. After enoximone, there was a significant decrease in SVR in both groups (group I: 26%; group II: 25% compared with the values obtained after halothane and isoflurane respectively). Halothane and isoflurane decreased CI significantly and to a similar degree (group I: 17%; group II: 17%). After the injection of enoximone CI increased significantly and reached control values in both groups. AO2 decreased significantly after administration of the volatile anaesthetics (group I: 19%; group II: 21%) and increased significantly after administration of enoximone, returning to control values. Halothane (7%) and isoflurane (13%) produced a significant increase in oxygen extraction. After bolus injection of enoximone oxygen extraction decreased significantly and returned to control value in group II. In group I enoximone decreased oxygen extraction significantly compared with control.Our results suggest that in the presence of halothane or isoflurane the phosphodiesterase inhibitor enoximone produces a comparable increase in cardiac output and decrease in systemic vascular resistance in patients with coronary artery disease.

The identification of disposition for malignant hyperthermia (MH) is performed by the halothane-caffeine contracture test in skeletal muscle. However, testing currently renders about 14% of the patients MH equivocal (MHE). To reduce this number the "ryanodine contracture test" has been proposed in addition to the established procedure. As all ryanodine preparations used until now are combinations of ryanodine and dehydroryanodine, we investigate in this study the effects of the now available high-purity ryanodine (HPR) in concentrations of 2,5 and 10 mumol/l.With all concentrations contractures appeared significantly earlier in MHS (malignant hyperthermia susceptible) than in MHN (malignant hyperthermia non-susceptible). However, only at 2 mumol/l a time overlap between both groups was not observed. By defining a time interval for MHS and MHN, three of the MHE patients could be assigned to MHS and three to MHN following their ryanodine-induced contractures.The ryanodine contracture test should be added to the current diagnostics of malignant hyperthermia.

Molecular genetic findings indicate genetic heterogeneity in susceptibility to malignant hyperthermia (MH). At present the in vitro contracture test (IVCT) is still the most reliable diagnostic procedure for MH susceptibility. It must be performed in a standardized fashion. METHODS. We investigated 350 patients (233 children and 117 adults) using the protocol of the European MH Group for the IVCT. The test results were classified as susceptible to MH (MHS), non-susceptible to MH (MHS), non-susceptible to MH (MHN) and equivocal (MHE), with an abnormal caffeine result designated MHEc and an abnormal halothane result designated MHEh. Reasons for the IVCT were a positive family history for MH susceptibility (n = 94), a MH reaction (n = 157), creatine kinase elevation unknown aetiology (n = 53) and different neuromuscular diseases (NMD, n = 46). Physical, neurological and laboratory work-up included serum enzymes, nerve conduction studies, electromyography and muscle biopsy evaluated by different techniques. Thirty-one children and 11 adults were MHS, while 152 children and 80 adults were MHN. MHE findings were obtained in 50 children and 26 adults. While the MHS and MHN groups are diagnostically safe, the equivocal group is not, with possible false-negative or false-positive interpretation. The high number of MHE findings most probably is explained by the high proportion of patients with NMD (53% of the children, 69% of the adults). RESULTS. In a group of 18 boys with Duchenne or Becker muscular dystrophy, ranging in age from 1.5 to 24 years, the IVCT results were twice MHS, once MHE, and MHN in the remaining 15 cases. In seven other boys with Duchenne or Becker muscular dystrophy, proven by molecular techniques, there were anaesthetic complications with MH-like symptoms. After administration of trigger substances, five out of the seven suffered a cardiac arrest, two of whom died. In the surviving five boys the IVCT results were three times MHN, once MHE and once MHS. Most probably these boys suffered from effects of succinylcholine, possibly potentiated by other trigger substances. The adverse cardiac reactions are attributed to triggered rhabdomyolysis with associated hyperkalemia but not a primary hereditary disposition to MH.In patients with NMD, MHS and MHE test results do not indicate a hereditary, heterogeneous disposition to MH; the majority will be caused by a secondary induced disturbance of calcium homoeostasis in the diseased muscle cells. These results do, however, indicate the following: (1) Patients with NMD exposed to trigger substances are at higher risk than the general population for MH-like episodes, including sudden death. (2) NMD therefore should be diagnosed as early as possible and patients should not be exposed to trigger substances when alternatives are at hand. (3) Diagnostic procedures in patients having suffered an MH-like episode should include IVCT and special investigations to exclude or substantiate other NMD. The work-up may be changed if a family member is properly classified as MH susceptible. (4) In patients with known NMD there is no indication for performing IVCT, since the results may even be misleading.