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Daten zur malignen Hyperthermie (MH) werden auf freiwilliger Basis USA- und Kanada-weit im North American Malignant Hyperthermia Registry of the United States (MHAUS) dokumentiert. Dabei fanden sich fur den Zeitraum von 1987–2006 bei 291 Ereignissen ein Herz-Kreislauf-Stillstand bei 2,7 % der Patienten und eine Sterblichkeit von 1,4 %. Wissenschaftler aus den USA legen jetzt aktuelle Zahlen vor.

The performance of caudal injection (CI) has become a routine part of pediatric anesthesia. The intraoperative and immediate postoperative complications of CIs have been reported extensively. Although the long-term consequences of CI are unknown, they may include the development of epidermoid tumors in the spinal canal. Such tumors have been attributed to tissue coring (the process by which pieces of tissue are removed by a needle as it passes through the tissue) and the subdural deposition of such tissue.In this study, we examine the internal needle of 20-gauge i.v. cannulae from 50 CIs for evidence of tissue coring.We found a total coring incidence of 54% (95% confidence interval = 40-68%). Epidermal tissue was present in 33% of the positive samples. Fat was present in 67% of the positive samples and bloody material in 26%. This study provides an estimate (with a 95% confidence interval) of the rate of coring during CI performed with hollow point needles.These findings suggest that technical modifications may improve patient safety. The results also have implications for long-term follow-up of caudal anesthetics. Techniques for reducing the incidence of tissue coring during the performance of CI are discussed.

This randomized blinded study tested the hypothesis that equipotent doses of vecuronium and mivacurium given in combination could achieve onset times to 90% neuromuscular block (B90) and intubation scores similar to succinylcholine. Thirty children were randomly assigned to one of three groups as follows. Group Sux received a single dose (1 mg.kg-1) of succinylcholine followed by normal saline. Group V1M1 received 0.08 mg.kg-1 of vecuronium followed by 0.1 mg.kg-1 of mivacurium. Group V2M2 received 0.16 mg.kg-1 of vecuronium followed by 0.2 mg.kg-1 of mivacurium. Anaesthesia consisted of propofol, fentanyl, and nitrous oxide. Neuromuscular response was monitored by adductor pollicis electromyography (Datex NMT). Sixty s after administration of the first injection, the laryngoscopy began, with the anaesthesiologist scoring the ease of intubation on a four category scale as excellent, good, poor, or inadequate. Time from injection to B90 was 39 (2.6)s after succinylcholine, which was not significantly different from 48 (3.5)s after vecuronium 0.16 mg.kg-1 and mivacurium 0.2 mg.kg-1 (V2M2). Mean time to B90 for group V1M1 was 64 (4.7)s, which was significantly different from that in group Sux. The intubation score was 'excellent' for all patients in groups Sux and V2M2 and for only seven of ten patients in group V1M1. Only combination of vecuronium (0.16 mg.kg-1) and mivacurium (0.2 mg.kg-1) provided rapid onset of neuromuscular blockade and excellent intubating conditions comparable to succinylcholine 1 mg.kg-1. This combination did result in prolonged recovery times.

The pharmacokinetics of atracurium were studied in infants and children anaesthetized with isoflurane and nitrous oxide in oxygen. There were no significant differences in volume of distribution (area) (139 v. 152 ml kg-1), clearance (5.1 v. 5.3 ml kg-1 min-1), T1/2 alpha (2.1 v. 2.0 min), or T1/2 beta (19.1 v. 20.3 min) between children with normal hepatic and renal function and those with moderately impaired hepatic function presenting for hepatic transplantation. There were significant differences in volume of distribution (area) (176 v. 139 ml kg-1) and in clearance of atracurium (9.1 v. 5.1 ml kg-1 min-1) between infants and children with normal excretory function. In infants the clearance of atracurium in ml m-2 min-1 (153 v. 133) tended to be greater and the T1/2 alpha and T1/2 beta tended to be shorter (1.0 v. 2.0 and 13.6 v. 19.1) than in children with normal excretory function; however, these trends did not reach statistical significance. Plasma laudanosine concentration was around 100 ng ml-1 greater in patients with liver disease than in normal children from 15-45 min following a bolus of atracurium 0.5 mg kg-1.

The purpose of this study was to determine: (a) whether a difference in the inspired median effective dose (ED,50) for halothane exists between 15-day-old and 30-day-old rats, (b) whether halothane concentrations in the brain and heart, associated with anesthesia and cardiac failure, differ as a function of age, and (c) the cardiovascular index for halothane (i.e., the ratio of the halothane concentration in the heart at cardiac failure and the halothane concentration in the heart at anesthesia) for the two groups of young rats. Mean EDI50 of halothane was determined in 15-, 30-, and 60-day-old rats by testing for movement and lack of movement (anesthesia) in response to tail clamping using the nonparametric method of Waud. Tissue concentrations of halothane (mg/100 g) were measured by gas chromatography at the end points of anesthesia and cardiovascular failure. Water content in the brain (as a function of age) was determined in separate groups of 15-, 30-, and 60-day-old rats. The ED,50 for halothane was greater in the 15-day-old rats than in the 30-day-old rats (p

The neuromuscular effects of doxacurium were studied in 26 children during halothane-nitrous oxide-oxygen anesthesia. Neuromuscular blockade was measured using electromyographic activity of the adductor pollicis muscle after supramaximal stimulation of the ulnar nerve at 2 Hz for 2 seconds at 10-second intervals. To estimate the cumulative dose-response relation, nine patients received incremental doses of doxacurium (2.5-10 micrograms/kg); nine patients received 27.5 micrograms/kg (the estimated ED95); eight patients received 50 micrograms/kg (1.8 X ED95). The ED25, ED50, ED75, and ED95 (estimated from linear regression plots of log dose vs probit of effect) were 11.5, 14.8, 19.0, and 27.3 micrograms/kg, respectively. Clinical duration (T25) was 27.8 +/- 10.3 (mean +/- SD) minutes at 1 X ED95 and 50.6 +/- 15.6 minutes at 1.8 X ED95. Time to recovery of the train-of-four ratio to 0.75 was 63.1 +/- 32.9 minutes at 1 X ED95 and 108.5 +/- 25.7 minutes at 1.8 X ED95. There were no significant changes in heart rate or mean arterial pressure after bolus administration of any dose of doxacurium.

We were interested in determining the dose-response relationship of atracurium in children (2-10 yr) during nitrous oxide-isoflurane anesthesia (1%) and the atracurium infusion rate required to maintain about 95% neuromuscular blockade during nitrous oxide-halothane (0.8%), nitrous oxide-isoflurane (1%), or nitrous oxide-narcotic anesthesia. Neuromuscular blockade was monitored by recording the electromyographic activity of the adductor pollicis muscle resulting from supramaximal stimulation at the ulnar nerve at 2 Hz for 2 sec at 10-sec intervals. To estimate dose-response relationships, three groups of five children received 80, 100, 150 micrograms/kg atracurium, respectively. During isoflurane anesthesia, the neuromuscular block produced by 80 micrograms/kg was 23.6% +/- 6.5 (mean +/- SEM), by 100 micrograms/kg was 45% +/- 7.2, and by 150 micrograms/kg was 64% +/- 8.7. The ED50 and ED95 (estimated from linear regression plots of log dose vs probit of effect) were 120 micrograms/kg and 280 micrograms/kg, respectively. At equipotent concentrations, halothane and isoflurane augment atracurium neuromuscular block to the same extent, compared to narcotic anesthesia. Atracurium steady-state infusion requirements averaged 6.3 +/- 0.6 micrograms . kg-1 . min-1 during halothane or isoflurane anesthesia; the requirements during balanced anesthesia were 9.3 +/- 0.8 micrograms . kg-1 . min-1 (P less than 0.05). There was no evidence of cumulation during prolonged atracurium infusion.

We measured uptake of halothane (the fraction of halothane in expired gas divided by the fraction of halothane in inspired gas, FE/FI) with a mass spectrometer over time in 7 infants less than 3 months of age. FE/FI for halothane in these infants increased more rapidly than has been described in adults by others. In addition, we developed a mathematical model for halothane uptake and distribution that incorporates age-dependent anatomic and physiologic parameters (alveolar ventilation, functional residual capacity, cardiac output, brain volume, etc). The model closely predicts FE/FI for halothane measured in the infants. At 5 min observed FE/FI was 0.67, at 15 min observed FE/FI was 0.80, while the predicted FE/FI values were 0.65 and 0.82, respectively. The model predicts that the myocardial and brain halothane concentrations will increase more rapidly in the infant than in the adult. Achievement of high myocardial halothane concentrations early in the anesthetic induction may cause the hypotension and bradycardia commonly seen in infants. Sensitivity of the infant myocardium to halothane would further exacerbate the effect of more rapid myocardial uptake.

Mivacurium chloride is a new, short-acting nondepolarizing neuromuscular blocking agent presently undergoing clinical evaluation. The neuromuscular effects of mivacurium and suxamethonium given by bolus and infusion were compared in adult patients during nitrous oxide-oxygen-opioid anaesthesia. Neuromuscular block was monitored by recording the compound electromyogram of the adductor pollicis muscle resulting from supramaximal train-of-four stimuli applied to the ulnar nerve. Time to onset of complete block and recovery to T5 were significantly shorter for suxamethonium than for mivacurium (1.0 (0.1) v. 2.5 (0.3) min and 6.4 (0.7) v. 17.5 (1.8) min; mean (SEM]. Conditions for tracheal intubation were similar in the two groups although intubation was performed 0.75-1.3 min later following mivacurium. The infusion rate required to maintain neuromuscular block was 88.6 (10.4) micrograms kg-1 min-1 for suxamethonium and 7.8 (1.2) micrograms kg-1 min-1 for mivacurium. There was a significant negative correlation between recovery to T5 and infusion rate for mivacurium and for suxamethonium. It was equally easy to titrate the infusion rate to the desired degree of block in each group. The recovery index (T25-T75) after the infusion stopped was similar in patients who received mivacurium and those who received suxamethonium.

The role of the liver and the kidney in alfentanil metabolism has not been defined. The effects of cholestatic hepatic disease and chronic renal failure on the pharmacokinetics of alfentanil were evaluated in 9 children undergoing liver transplantation and 10 children undergoing kidney transplantation. These findings were compared with data from 10 children with normal hepatic and renal function undergoing other surgical procedures. There was no statistical difference among the 3 groups with respect to apparent volume of distribution, half-life, or clearance. In a subgroup of 3 patients undergoing liver transplantation alfentanil kinetics were determined both before and after the allograft was incorporated into the recipient's circulation. Though both volume of distribution and elimination half-life increased in the posttransplantation period, only the decrease in clearance was statistically significant. Thus, it appears that alfentanil may be a useful anesthetic agent in pediatric patients with cholestatic hepatic disease or chronic renal failure. The dose of alfentanil in these patients need not be altered except in the period immediately after liver transplantation.

The neuromuscular and cardiovascular effects of mivacurium were studied in 90 adult patients during nitrous oxide-oxygen-isoflurane (n = 45, ISO group) and nitrous oxide-oxygen-narcotic (n = 45, BAL group) anesthesia. Neuromuscular blockade was measured using electromyographic activity of the adductor pollicis muscle after supramaximal stimulation of the ulnar nerve at 2 Hz for 2 seconds at 10-second intervals. To estimate dose-response relations, three subgroups of nine patients in the ISO group received mivacurium doses of 0.025, 0.03, and 0.04 mg/kg, respectively. Similarly, three subgroups of nine patients in the BAL group received mivacurium doses of 0.03, 0.04, and 0.05 mg/kg, respectively. The ED50 and ED95 of mivacurium in each group were estimated from linear regression plots of log dose vs probit of maximum percentage depression of neuromuscular function. The estimated ED50 values for the ISO and BAL groups were 0.029 and 0.041 mg/kg, respectively. The estimated ED95 values for the ISO and BAL groups were 0.045 and 0.058 mg/kg, respectively. Recovery indexes were measured in 26 patients who received ED95 or greater doses of mivacurium in either the ISO or BAL groups. The recovery index was shorter in the BAL group (5.5 +/- 1.6 minutes [n = 10]), than in the ISO group (7.4 +/- 3.0 minutes [n = 16]). The addition of isoflurane (0.5-0.75% end-tidal concentration) to nitrous oxide-narcotic anesthesia augments the degree of neuromuscular blockade from a given dose of mivacurium and also prolongs the recovery index.

The role of the kidney in sufentanil elimination or metabolism has not been defined. The effects of chronic renal failure (CRF) on the pharmacokinetic profile of sufentanil were evaluated in six adolescent patients undergoing renal transplantation, and these findings were compared with data from age-matched control patients with normal renal function who were undergoing other surgical procedures. Patients with CRF weighed significantly less than did the control patients (28.7 +/- 5.7 vs 44.7 +/- 12.9 kg [mean +/- SD]). Although there was no statistical difference in the rate of clearance or apparent volume of distribution and half-life between the two groups, clearance and half-life were more variable among patients with CRF. In these patients, therefore, sufentanil dose must be carefully administered based on responses elicited in individual patients.

The neuromuscular effects of atracurium were studied in 25 infants anesthetized with 1.0% end-tidal halothane and N2O-O2. Neuromuscular blockade was monitored by recording the electromyographic activity of the adductor pollicis muscle resulting from supramaximal stimulation of the ulnar nerve at 2 Hz for 2 sec at 10-sec intervals. To estimate dose-response relationships, three groups of five infants received 60, 80, and 100 micrograms/kg atracurium, respectively; another ten infants received 300 micrograms/kg (2 X ED95). The neuromuscular block produced by 60 micrograms/kg was 27% +/- 10.9 (SEM), by 80 micrograms/kg was 34% +/- 8.0 and from 100 micrograms/kg was 70% +/- 8.3. The ED50 and ED95 (estimated from linear regression plots of log dose vs probit of effect) were 85 micrograms/kg and 150 micrograms/kg, respectively. Neuromuscular blockade lasted 23 +/- 1.6 min at 1 X ED95 and 32.5 +/- 5.2 min at 2 X ED95. Changes in heart rate and mean arterial pressure were clinically insignificant.

We were interested in determining the effect of enflurane, halothane, and isoflurane on the uptake and removal of 5-hydroxytryptamine (5-HT) and phenylethylamine (PEA) from the lung. Isolated rabbit lungs were perfused in a recirculating system in vitro with 0.1 microM [14C]5-HT or 0.1 microM [14C]PEA in Krebs-Ringer solution. The rate of removal and percentage of removal of the bioamines were determined before and after either 1, 2, or 4 MAC multiples of the potent anesthetics. Because of variation in removal of bioamines among lungs from different animals, the effects of anesthetics on bioamine removal were determined by calculating the percentage of inhibition of removal using data from the control and test period for each lung. At 2 MAC concentrations, the anesthetics inhibited 5-HT removal 11.1%, at 4 MAC concentrations the anesthetics inhibited 5-HT removal 29.8% and significantly prolonged the half-life (t 1/2) of 5-HT removal. There was significant (10.8%) inhibition of PEA removal at 4 MAC concentrations for the three anesthetics. As uptake of 5-HT is the rate-limiting step in 5-HT removal, these data demonstrate a uniform depression of 5-HT uptake by the three potent anesthetics. The rate-limiting step of PEA uptake, metabolism by monoamine oxidases, is inhibited at 4 MAC concentrations of anesthetics.

The in vitro rates of metabolism of mivacurium chloride and succinylcholine in pooled human plasma were compared. In addition, the rate of metabolism of mivacurium in buffered solutions of butyrylcholinesterase (E.C. 3.1.1.8) and acetylcholinesterase (E.C. 3.1.1.7) was determined. Succinylcholine concentrations were measured spectrophotometrically, and mivacurium concentrations were determined with a high-pressure liquid chromatographic assay. The hydrolysis of mivacurium in plasma followed first-order kinetics, and the rate of hydrolysis decreased as plasma was serially diluted. The Michaelis-Menten constant (Km) for mivacurium metabolism in plasma was 245 mumol/L, and the maximum velocity (Vmax) was 50 U/L; the Km for succinylcholine was 37 mumol/L, and Vmax was 74 U/L. At comparable multiples of the Km the hydrolysis rate of mivacurium was 70% of that of succinylcholine. Mivacurium was metabolized significantly in solutions containing butyrylcholinesterase, but only minimally in solutions containing acetylcholinesterase.

The potency of atracurium was determined in adolescents and children during nitrous oxide-halothane and nitrous oxide-thiopentone-fentanyl anaesthesia using single dose-response curves. Dose-response curves were parallel. The effective doses producing 95% twitch depression (ED95) (mg kg-1) during nitrous oxide-halothane were larger in younger children than in the adolescents. Halothane (0.8% end-tidal) did not significantly potentiate atracurium when compared with thiopentone-fentanyl. On a microgram m-2 basis there was no difference in the ED95 between patients of different age or those anaesthetized with different techniques. At approximately 95% twitch depression intubating conditions were excellent in all groups. Minimal cardiovascular effects were noted at several multiples of the ED95.

The neuromuscular action of ranitidine, an H2-receptor antagonist, was investigated by determining its effect on atracurium-induced neuromuscular blockade in urethane-anesthetized and mechanically ventilated male Sprague-Dawley rats. An intravenous bolus and an infusion of atracurium were administered to produce a stable 93 +/- 5% (n = 11) neuromuscular blockade as judged by tibialis anterior muscle twitch response. Ranitidine administered as a 1, 5, or 10 mg/kg normal body weight IV bolus during continuous atracurium infusion produced marked antagonism of neuromuscular paralysis. The percentage of antagonism (25 +/- 9%; n = 4; 53 +/- 19%, n = 4; and 79 +/- 9%, n = 3, respectively) was linearly related to the dose of ranitidine (r = 0.86, P less than 0.05). These results suggest that IV ranitidine has a significant anticholinesterase action against atracurium-induced neuromuscular blockade.