F.R. Ellis

Comparison of propofol and thiopentone for laryngeal mask insertion

Conditions for insertion of the laryngeal mask were assessed following induction of anaesthesia with either propofol 2.5 mg/kg or thiopentone 4.0 mg/kg in 80 patients premedicated with diazepam 10 mg. Insertion following induction with thiopentone resulted in a greater incidence of gagging (p < 0.01). The use of additional induction agent, where necessary, resulted in no ultimate significant difference between the groups for the provision of satisfactory conditions.

Recognizing and managing a malignant hyperthermia crisis: guidelines from the European Malignant Hyperthermia Group

Survival from a malignant hyperthermia (MH) crisis is highly dependent on early recognition and prompt action. MH crises are very rare and an increasing use of total i.v. anaesthesia is likely to make it even rarer, leading to the potential risk of reduced awareness of MH. In addition, dantrolene, the cornerstone of successful MH treatment, is unavailable in large areas around the world thereby increasing the risk of MH fatalities in these areas. The European Malignant Hyperthermia Group collected and reviewed all guidelines available from the various MH centres in order to provide a consensus document. The guidelines consist of two textboxes: Box 1 on recognizing MH and Box 2 on the treatment of an MH crisis.

Evidence for related myopathies in exertional heat stroke and malignant hyperthermia.

Malignant hyperthermia may be a human stress syndrome, of which heat stroke is one manifestation. Two men in military service who had episodes of exertional heat stroke, and their immediate family members, were tested for susceptibility to malignant hyperthermia by in-vitro contracture tests on skeletal muscle samples. Muscle from both patients had a normal response to caffeine but an abnormal response to halothane. Muscle from the father of one patient had an abnormal response to halothane, and that from the father of the second patient had an abnormal response to ryanodine. The results indicate that clinical heat stroke may be associated with an underlying inherited abnormality of skeletal muscle that is similar, but not identical, to that of malignant hyperthermia.

Screening for Malignant Hyperpyrexia

The methods used to screen patients for malignant hyperpyrexia at present are not sufficiently accurate. This paper reports more specific methods of detecting patients liable to develop malignant hyperpyrexia. A motor-point muscle biopsy is performed for histopathological examination and to detect muscle contracture in vitro after exposure to halothane and suxamethonium.

Multiple interacting gene products may influence susceptibility to malignant hyperthermia

Malignant hyperthermia (MH) is a potentially lethal disorder triggered in susceptible individuals on exposure to common anaesthetic agents. Crises reflect the consequences of disturbed skeletal muscle calcium homeostasis. MH is an autosomal dominant, genetically heterogeneous trait. Defects in a single major gene have been assumed to determine susceptibility status in individual families. However, in some pedigrees phenotypic and genotypic data are discordant. One explanation, in contrast to the current genetic model, is that susceptibility is dependent upon the effects of more than one gene. Using the transmission disequilibrium test we assessed the involvement of 8 MH candidate loci (RYR1, CACNA1S, CACNA2D1, MHS4 at 3q13.1, MHS6 at 5p, LIPE, DM1, dystrophin) by analysis of data from 130 MH nuclear families. Results suggested that variations in more than one gene may influence MH susceptibility in single families.

RYR1 mutations in UK central core disease patients: more than just the C-terminal transmembrane region of the RYR1 gene

The congenital myopathies are a group of disorders that are difficult to distinguish. Diagnosis is frequently dependent on the result of histological examination of muscle biopsy specimens in conjunction with clinical diagnosis. There is a significant degree of overlap in the clinical features of different congenital myopathies: identification of genetic determinants may therefore aid in establishing a firm diagnosis. Central core disease (CCD) is a rare congenital myopathy. Histologically, using oxidative enzyme stains, it is identified by the abundance of central cores, characterised by localised areas of mitochondrial depletion and sarcomere disorganization exclusively in type 1 skeletal muscle fibres, and extending throughout their length. Cores are often central and unique, but may be eccentric or multiple within one fibre. Affected patients may present with congenital muscle hypotonia, pronounced proximal weakness, delayed motor development, and slightly elevated creatine kinase (CK) levels. In addition, skeletal anomalies such as congenital hip displacement and scoliosis are frequent. Later in life muscle strength may improve, but in rare cases progressive muscle weakness is observed. Respiratory insufficiency is rare.1,2 Overall, the disorder demonstrates significant phenotypic variability; in a study of 13 cases, as many as 40% of patients with histological signs of disease were clinically asymptomatic.3 CCD is predominantly reported as an autosomal dominant trait. However, there is evidence that inheritance may be autosomal recessive in some families,4,5 and sporadic cases have been documented.6,7 It is recognised as the primary disorder associated and allelic with the pharmacogenetic disorder malignant hyperthermia (MH).8 However, characteristic muscle cores have been reported in association with several other myopathies, namely multi-mini core disease (MmD), nemaline myopathy, and hypertrophic cardiomyopathy. All have additional definitive characteristics in their own right, although in some cases the phenotypic boundaries are difficult to assert. MH also shows autosomal …

Clinical presentation of suspected malignant hyperthermia during anaesthesia in 402 probands

As anaesthetists have become more aware of malignant hyperthermia the mortality rate has fallen, but concommitantly the number of dubious and aborted cases has increased. All probands who developed a suspected malignant hyperthermia reaction during anaesthesia and subsequently underwent muscle biopsy were classified according to the clinical presentation. A probability for malignant hyperthermia can be calculated, using the classification, for each type of clinical presentation; this varied from 0.96 to 0.07. Certain clinical features were found to be of more value as predictors than others; these included a high creatine kinase and myoglobinuria. The accuracy of prediction depends on a clear contemporaneous description of the clinical events.

European Malignant Hyperthermia Group guidelines for investigation of malignant hyperthermia susceptibility

It is 30 yr since the British Journal of Anaesthesia published the first consensus protocol for the laboratory diagnosis of malignant hyperthermia susceptibility from the European Malignant Hyperthermia Group. This has subsequently been used in more than 10 000 individuals worldwide to inform use of anaesthetic drugs in these patients with increased risk of developing malignant hyperthermia during general anaesthesia, representing an early and successful example of stratified medicine. In 2001, our group also published a guideline for the use of DNA-based screening of malignant hyperthermia susceptibility. We now present an updated and complete guideline for the diagnostic pathway for patients potentially at increased risk of developing malignant hyperthermia. We introduce the new guideline with a narrative commentary that describes its development, the changes to previously published protocols and guidelines, and new sections, including recommendations for patient referral criteria and clinical interpretation of laboratory findings.

Genetic heterogeneity and HOMOG analysis in British malignant hyperthermia families.

Malignant hyperthermia (MH) is an autosomal dominant genetic condition that presents in susceptible people undergoing general anaesthesia. The clinical disorder is a major cause of anaesthetic morbidity and mortality. The UK Malignant Hyperthermia Group has performed genetic linkage analysis on 20 large, well defined malignant hyperthermia families, using hypervariable markers on chromosome 19q13.1, including the candidate MH gene RYR1, the gene coding for the skeletal muscle ryanodine receptor protein. The results were analysed using LINKAGE to perform two point and multipoint lod scores, then HOMOG to calculate levels of heterogeneity. The results clearly showed genetic heterogeneity between MH families; nine of the families gave results entirely consistent with linkage to the region around RYR1 while the same region was clearly excluded in three families. In the remaining eight MHS families there were single recombinant events between RYR1 and MH susceptibility. HOMOG analysis was of little added benefit in determining the likelihood of linkage to RYR1 in these families. This confirmation of the presence of heterogeneity in the UK MH population, along with the possibility of the presence of two MH genes in some pedigrees, indicates that it would be premature and potentially dangerous to offer diagnosis of MH by DNA based methods at this time.

Evaluation of local anaesthetic blockade of the lateral femoral cutaneous nerve

An assessment of local anaesthetic blockade of the lateral femoral cutaneous nerve using a standard technique was made. The rate of successful blockade was high, but the area of sensory loss was inconsistent between patients and was more anterior and distal than described in textbooks of anatomy.