BackgroundMalignant hyperthermia (MH) is a rare pharmacogenetic disorder which is characterized by life-threatening metabolic crises during general anesthesia. Classical triggering substances are volatile anesthetics and succinylcholine (SCh). The molecular basis of MH is excessive release of Ca2+ in skeletal muscle principally by a mutated ryanodine receptor type 1 (RyR1). To identify factors explaining the variable phenotypic presentation and complex pathomechanism, we analyzed proven MH events in terms of clinical course, muscle contracture, genetic factors and pharmocological triggers.MethodsIn a multi-centre study including seven European MH units, patients with a history of a clinical MH episode confirmed by susceptible (MHS) or equivocal (MHE) in vitro contracture tests (IVCT) were investigated. A test result is considered to be MHE if the muscle specimens develop pathological contractures in response to only one of the two test substances, halothane or caffeine. Crises were evaluated using a clinical grading scale (CGS), results of IVCT and genetic screening. The effects of SCh and volatile anesthetics on Ca2+ release from sarcoplasmic reticulum (SR) were studied in vitro.ResultsA total of 200 patients met the inclusion criteria. Two MH crises (1%) were triggered by SCh (1 MHS, 1 MHE), 18% by volatile anesthetics and 81% by a combination of both. Patients were 70% male and 50% were younger than 12 years old. Overall, CGS was in accord with IVCT results. Crises triggered by enflurane had a significantly higher CGS compared to halothane, isoflurane and sevoflurane. Of the 200 patients, 103 carried RyR1 variants, of which 14 were novel. CGS varied depending on the location of the mutation within the RyR1 gene. In contrast to volatile anesthetics, SCh did not evoke Ca2+ release from isolated rat SR vesicles.ConclusionsAn MH event could depend on patient-related risk factors such as male gender, young age and causative RyR1 mutations as well as on the use of drugs lowering the threshold of myoplasmic Ca2+ release. SCh might act as an accelerant by promoting unspecific Ca2+ influx via the sarcolemma and indirect RyR1 activation. Most MH crises develop in response to the combined administration of SCh and volatile anesthetics.

Malignant hyperthermia is a potentially fatal condition, in which genetically predisposed individuals develop a hypermetabolic reaction to potent inhalation anaesthetics or succinylcholine. Because of the rarity of malignant hyperthermia and ethical limitations, there is no evidence from interventional trials to inform the optimal perioperative management of patients known or suspected with malignant hyperthermia who present for surgery. Furthermore, as the concentrations of residual volatile anaesthetics that might trigger a malignant hyperthermia crisis are unknown and manufacturers' instructions differ considerably, there are uncertainties about how individual anaesthetic machines or workstations need to be prepared to avoid inadvertent exposure of susceptible patients to trigger anaesthetic drugs. The present guidelines are intended to bundle the available knowledge about perioperative management of malignant hyperthermia-susceptible patients and the preparation of anaesthesia workstations. The latter aspect includes guidance on the use of activated charcoal filters. The guidelines were developed by members of the European Malignant Hyperthermia Group, and they are based on evaluation of the available literature and a formal consensus process. The most crucial recommendation is that malignant hyperthermia-susceptible patients should receive anaesthesia that is free of triggering agents. Providing that this can be achieved, other key recommendations include avoidance of prophylactic administration of dantrolene; that preoperative management, intraoperative monitoring, and care in the PACU are

Background Postoperative bleeding is a major problem in children undergoing complex pediatric cardiac surgery. The primary aim of this prospective observational study was to evaluate the effect of an institutional approach consisting of early preventive fibrinogen, prothrombin complex and platelets administration on coagulation parameters and postoperative bleeding in children. The secondary aim was to study the rate of re-intervention and postoperative transfusion, the occurrence of thrombosis, length of mechanical ventilation, ICU stay and mortality. Methods In fifty children (age 0–6 years) with one or more predefined risk factors for bleeding after cardiopulmonary bypass (CPB), thrombelastography (TEG) and standard coagulation parameters were measured at baseline (T1), after CPB and reversal of heparin (T2), at sternal closure (T3) and after 12 h in the ICU (T4). Clinical bleeding was evaluated by the surgeon at T2 and T3 using a numeric rating scale (NRS, 0–10). Results After CPB and early administration of fibrinogen, prothrombin complex and platelets, the clinical bleeding evaluation score decreased from a mean value of 6.2 ± 1.9 (NRS) at T2 to a mean value of 2.1 ± 0.8 at T3 (NRS; P <  0.001). Reaction time (R), kinetic time (K), maximum amplitude (MA) and maximum amplitude of fibrinogen (MA-fib) improved significantly (P <  0.001 for all), and MA-fib correlated significantly with the clinical bleeding evaluation (r = 0.70, P <  0.001). The administered total amount of fibrinogen (mg kg− 1) correlated significantly with weight (r = − 0.42, P = 0.002), priming volume as percentage of estimated blood volume (r = 0.30, P = 0.034), minimum CPB temperature (r = − 0.30, P = 0.033) and the change in clinical bleeding evaluation from T2 to T3 (r = 0.71, P <  0.001). The incidence of postoperative bleeding (> 10% of estimated blood volume) was 8%. No child required a surgical re-intervention, and no cases of thrombosis were observed. Hospital mortality was 0%. Conclusion In this observational study of children with an increased risk of bleeding after CPB, an early preventive therapy with fibrinogen, prothrombin complex and platelets guided by clinical bleeding evaluation and TEG reduced bleeding and improved TEG and standard coagulation parameters significantly, with no occurrence of thrombosis or need for re-operation. Trial registration German Clinical Trials Register DRKS00018109 (retrospectively registered 27th August 2019).

The Narcotrend monitor indicated a Narcotrend Index in most infants and young children starting from 4 months with significant correlation to and acceptable prediction probability for minimal alveolar sevoflurane concentration.