H. Ørding

A Clinical Grading Scale to Predict Malignant Hyperthermia Susceptibility

Background:The diagnosis of an acute malignant hyperthermia reaction by clinical criteria can be difficult because of the nonspecific nature and variable incidence of many of the clinical signs and laboratory findings. Development of a standardized means for estimating the qualitative likelihood of malignant hyperthermia in a given patient without the use of specialized diagnostic testing would be useful for patient management and would promote research into improved means for diagnosing this disease. Methods:Using the Delphi method and an international panel of 11 experts on malignant hyperthermia, a multifactor malignant hyperthermia clinical grading scale comprising standardized clinical diagnostic criteria was developed for classification of existing records and for application to new patients. Results:This scale ranks the qualitative likelihood that an adverse anesthetic event represents malignant hyperthermia (malignant hyperthermia event rank) and that, with further investigation of family history, an individual patient will be diagnosed as malignant hyperthermia susceptible (malignant hyperthermia susceptibility rank). The assigned rank represents a lower bound on the likelihood of malignant hyperthermia. The clinical grading scale requires the anesthesiologist to judge whether specific clinical signs are appropriate for the patients medical condition, anesthetic technique, and surgical procedure. Conclusions:The malignant hyperthermia clinical grading scale is recommended for use as an aid to the objective definition of this disease. Its use may improve malignant hyperthermia research by allowing comparisons among well-defined groups of patients. This clinical grading system provides a new and comprehensive clinical case definition for the malignant hyperthermia syndrome.

Analysis of anaesthesia in patients suspected to be susceptible to malignant hyperthermia before diagnostic in vitro contracture test

Background: It is well known that patients susceptible to malignant hyperthermia (MH) do not always develop clinical signs of MH at their first anaesthetic. Large material concerning this epidemiological problem do not exist. Therefore, we undertook the present investigation at the Danish Malignant Hyperthermia Register.

Discordance between malignant hyperthermia susceptibility and RYR1 mutation C1840T in two Scandinavian MH families exhibiting this mutation.

The ryanodine receptor 1 (RYR1) mutation C1840T has been reported to segregate with malignant hyperthermia (MH) susceptibility in several families. We have investigated several Scandinavian MH families with respect to five different RYR1 mutations reported to cause predisposition to MH, and we here report on two of the families in which the C1840T mutation was detected. In these two families there was recombination between MH susceptibility and this mutation in one and three individuals, respectively. These findings may suggest that it is necessary to reconsider the specificity of the IVCT and the role of C1840T as a cause of MH susceptibility in some families exhibiting this mutation.

How do anaesthesiologists treat malignant hyperthermia in a full‐scale anaesthesia simulator?

Background: Clinical malignant hyperthermia (MH) is rare and usually occurs unexpectedly. Prompt diagnosis and correct treatment is crucial for survival of the patient developing fulminant MH. The aims of the present study were to investigate whether anaesthesiologists could make a correct diagnosis of MH and to evaluate their treatment of fulminant MH in a simulator.

Dose‐response Curves for Vecuronium during Halothane and Neurolept Anaesthesia: Single Bolus versus Cumulative Method

The purpose of this study was to compare the incremental, cumulative dose method and the single bolus injection technique for construction of dose‐response curves for vecuronium. Dose‐response curves were determined in 77 patients divided into four groups according to the anaesthetic given and the method used for construction of dose‐response curves. The regression lines corresponding to the four dose‐response curves were found to be parallel. For vecuronium ED50 during neurolept anaesthesia was found to be 28 μg kg‐1 with the single bolus injection technique and 35.2 μg kg‐1 with the incremental, cumulative dose method (P<0.05). During halothane anaesthesia, ED50 was found to be 25.7 μg kg‐1 and 26.2 μg kg‐1, respectively (P>0.05). Potentiation of vecuronium by halothane was found with the cumulative method only. It is concluded that the incremental, cumulative dose method is not suitable for potency determinations of vecuronium.

Edrophonium and Neostigmine for Reversal of the Neuromuscular Blocking Effect of Vecuronium

The effect of edrophonium for reversal of the non‐depolarizing neuromuscular blockade produced by a continuous infusion of vecuronium was compared to that of neostigmine in 20 adult patients during neurolept anaesthesia. When antagonism was attempted at 10% twitch height recovery, reversal time to a train‐of‐four ratio of 0.7 was significantly shorter following neostigmine 0.04 mg/kg than after edrophonium 0.75 mg/kg (9.8 min and 18.7 min, respectively) but the same after edrophonium 1.5 mg/kg (10.3 min). There was no statistically significant difference in reversal time between neostigmine 0.04 mg/kg given at 10% twitch height and edrophonium 0.75 mg/kg given at 25% twitch height recovery (6.0 min). Additional doses of atropine were necessary following edrophonium 1.5 mg/kg.

4‐chloro‐m‐cresol test ‐ a possible supplementary test for diagnosis of malignant hyperthermia susceptibility

Background: In vitro contracture test (IVCT) for diagnosis of MH in our laboratory has a sensitivity of 100% and a specificity of 93%. The results are equivocal in 10–15%, and supplementary tests may thus be required. We have tested the hypothesis that 4‐chloro‐m‐cresol (4‐cmc) may be useful for a supplementary test.

Malignant Hyperthermia Triggered by Heating in Anaesthetized Pigs

Three malignant hyperthermia susceptible (MHS) and three normal Danish landrace pigs were heated using a water‐heated mattress, warm blankets and warm intravenous saline during anaesthesia with barbiturate and 50% nitrous oxide in oxygen. The MHS pigs developed typical malignant hyperthermia (MH) at a rectal temperature of 41.0 ± 0.7°C, whereas the normal pigs tolerated heating to the same temperature without any ill effects. Haemodynamic and metabolic findings during MH were similar to those previously reported for anaesthetic‐induced MH in pigs. Heat intolerance may thus be one factor in the genesis of MH.

Pretreatment with Non-Depolarizing Muscle Relaxants: The Influence on Neuromuscular Transmission and Pulmonary Function

The influence of pretreatment with non‐depolarizing muscle relaxants on the neuromuscular transmission was evaluated in 40 healthy, awake, non‐premedicated volunteers using train‐of‐four (TOF) nerve stimulation and measurement of vital capacity (VC), inspiratory force (IF), peak expiratory flow (PEF), and forced expiratory volume in the first second (FEV1). The subjects were randomly allocated to one offour groups: group I received pancuronium 0.01 mg/kg; group II pancuronium 0.015 mg/kg; group III gallamine 0.3 mg/kg, and group IV gallamine 0.4 mg/kg intravenously. TOF ratio decreased significantly in groups II, III, and IV but not in group I following precurarization. Median (25 and 75 percentiles) TOF ratios after pretreatment were 94 (92–96), 89 (86–93), 92 (89–93), and 93 (87–96), respectively. Overall there were decreases in VC, IF, and PEF, but only the decrease in PEF was statistically significant in all four groups. FEVl was unchanged. The most pronounced decrease in VC, IF, and PEF (11,29, and 29 %, respectively) was seen in one subject in group II with a TOF‐ratio of 63 following precurarization. Four subjects (20%) in groups IIand IVexperienced difficulty in breathing. All subjects were, however, able to maintain head lift for more than 10 s, and none needed respiratory support. Seventy percent of all subjects had various minor complaints as, for instance, blurred vision and difficulty in swallowing. It is concluded that the higher doses of pancuronium (0.015 mg/kg) and gallamine (0.4 mg/kg) cannot be recommended for routine precurarization.

Results of in vitro contracture testing of both parents of malignant hyperthermia susceptible probands

Background: Malignant Hyperthermia (MH) is regarded as a dominantly inherited condition. Therefore, most investigators do not test the second parent if the first parent is found to be MH susceptible (MHS). The purpose of this study was to validate this policy.