Physiological restitution after night-call duty in anaesthesiologists: impact on metabolic factors.

BACKGROUND: Several studies have shown impaired mental well-being and performance in physicians work on call, but knowledge of the physiological effects is scarce. The aims of the present study were to investigate if there was a metabolic stress response in the restitutional phase after night-call duty, indicating potential negative health effects, and determine whether there were differences between physician specialities. METHODS: Anaesthesiologists (n = 19) were compared with paediatricians/ear, nose and throat (ENT) surgeons (n = 18). On an ordinary workday, 1 and 3 days after work on night call, blood samples were taken for analysis of glucose, thyroid-stimulating hormone (TSH), free thyroxine, testosterone, insulin growth factor-1 (IGF-1), high- and low-density lipoprotein cholesterol (HDL and LDL), triglycerids (TG) and insulin. Saliva cortisol was sampled on an ordinary working day, a day including 16-h night call, the third day following, and for anaesthesiologists also on a day off work. RESULTS: TSH differed significantly between days in both groups, with a 26% lower level 1 day after on-call duty (P < 0.001). A 48% cortisol rise in the morning preceding night duty was found for paediatricians/ENT surgeons (P < 0.01). CONCLUSION: The significant dip in TSH level 24 h after night-call duty indicates a metabolic effect of working on night call and should be studied further. However, the levels were within the normal range and the overall results do not imply any serious metabolic changes and only minor differences were seen between specialist groups.

Male preponderance of patients testing positive for malignant hyperthermia susceptibility.

BACKGROUND: Malignant hyperthermia susceptibility is diagnosed using an in vitro contracture test (IVCT). In families in which the mutation is known, genetic tests are also available. The inheritance pattern is regarded as autosomal dominant, which predicts equal proportions of men and women affected. The aim of this study was to investigate whether there were sex differences in the diagnostic outcome of the 1407 patients tested for malignant hyperthermia in Sweden between 1985 and 2005. METHODS: Information about sex, diagnosis, IVCT result and kinship was analysed. Comparisons were made between the two sexes. Probands and relatives were analysed separately in order to eliminate bias caused by the type of surgery performed in the two sexes. RESULTS: Males, more than females, revealed a pathological outcome in IVCT. Amongst male relatives, the fraction of pathological outcome in IVCT was 0.70 [95% confidence interval (CI), 0.66-0.74]; the corresponding value for females was 0.40 (95% CI, 0.36-0.44). CONCLUSION: A significant difference was observed in the sex distribution of outcome of IVCT, with significantly more males revealing a pathological IVCT. This indicates the influence of one or several factors related to sex in the outcome of IVCT, for example different expression of calcium handling proteins in the sexes, a complex pattern of inheritance or unknown environmental factors.

Genetic recombination between malignant hyperthermia and calcium release channel in skeletal muscle.

Absolute linkage between the gene, on chromosome 19, for the calcium release channel (CRC) of the sarcoplasmic reticulum in skeletal muscle and malignant hyperthermia (MH) has been reported by other workers. In the present study of three Swedish Families informative with respect to this linkage relationship, definite recombinants were found in two families. We conclude that mutations in other genes than the CRC gene can cause the clinical picture of MH. Accordingly, MH appears to be genetically heterogeneous.

Clinical and muscle biopsy findings in malignant hyperthermia susceptibility.

Patients (155) were investigated for malignant hyperthermia susceptibility (MHS), by in vitro testing of muscle taken from the vastus medialis muscle. Histopathological and histochemical investigation of muscle was also performed. Ultrastructural investigation was performed in 13 MHS patients; 90% of the patients replied to a questionnaire concerning present or previous neuromuscular symptoms. The majority of MHS and MH negative (MHN) patients had no or only minor histopathological and histochemical abnormalities. Core-targetoid fibres were the only potentially important abnormalities found in MHS patients. There were no differences in neuromuscular symptoms between MHS, MHN and control patients, and most patients in both the MHS and MHN group were normal on clinical examination.

Investigation of malignant hyperthermia in Sweden.

One hundred and thirty patients from 52 families were investigated for susceptibility to malignant hyperthermia (MH). The diagnosis of MH susceptibility (MHS) was made by in vitro exposure of muscle to halothane and to caffeine, according to the protocol established by the European malignant hyperpyrexia group. In addition, 13 normal control biopsies were obtained from the same muscle and with the same anaesthesia as in the MH patients. These control results agree with and confirm the criteria formulated in the European MH group. The results are compared with our first 85 investigations performed prior to the establishment of the protocol. The main difference compared to the earlier material is the addition of an equivocal group (MHE), whose muscle reacted in vitro to either halothane or caffeine, but not both. All the families referred because of a fulminant MH reaction contained MHS or MHE members. There was a greater incidence of MH-negative families, suggesting an increased suspicion of MH amongst the clinicians.

Static v. dynamic tests in the in vitro diagnosis of malignant hyperthermia susceptibility.

In vitro contracture tests, in which muscle specimens are exposed to halothane or caffeine are, at present, the only generally accepted screening methods for the diagnosis of susceptibility to malignant hyperthermia (MHS). Static tests (performed with the muscle held at constant length) are used more commonly although, in addition, some MH investigation units use dynamic tests, in which the length of the specimen is varied. We have performed dynamic and static tests in parallel on muscle from 112 patients. The dynamic halothane test was more sensitive in discriminating between MHS and MH negative (MHN) individuals than the static halothane test. However, the dynamic caffeine test was less sensitive at discriminating between MHS and MHN individuals, and nothing is to be gained by including it in the investigation.

Methylxanthines reduce in vitro human overall platelet metabolism as measured by microcalorimetry.

The effect in vitro of caffeine, theophylline and enprofylline on overall platelet metabolism was investigated by a sensitive microcalorimetric method. Platelet heat production rate was found to be decreased significantly in the presence of any of the three methylxanthines in mM concentrations. Also lower caffeine concentration, as occurring during normal coffee intake, reduced platelet metabolism. These results show that, firstly, methylxanthines have a direct influence on platelet metabolism, and secondly, microcalorimetry can be used as a new and sensitive tool for investigating the influence of drugs on blood cell metabolism.

Microcalorimetric studies in malignant hyperpyrexia susceptible individuals.

In an attempt to develop a diagnostic test for malignant hyperpyrexia (MH) without the need for open muscle biopsy, we have investigated the change in heat production brought about when platelets and muscle are exposed to halothane and caffeine. Halothane 3% caused platelet aggregation, which was itself associated with heat production. Caffeine 4 mmol litre-1 decreased heat production in platelets from both MH susceptible and non-susceptible individuals. Muscle exposed to 4% halothane showed an increase in heat production in both types of tissue. There were no significant differences in heat production between MH-susceptible and non-susceptible tissue in any of the tests.

Malignant hyperpyrexia and sudden death.

Two teenage boys, brothers, died suddenly within 2 months of each other. No clear cause of death could be identified in either case. Because of previous reports of the association between malignant hyperpyrexia and sudden death in otherwise healthy young men, we examined the parents. The father was found to be malignant hyperpyrexia-susceptible.

Investigation of malignant hyperthermia in Denmark and Sweden.

Units for the investigation of susceptibility to malignant hyperthermia (MH) were set up in Denmark in 1977 and in Sweden in 1981. Two hundred and ten patients from 76 families have been investigated. The diagnosis of MH susceptibility (MHS) was made by in vitro exposure of muscle from vastus medialis to halothane and to caffeine. MHS criteria for the patients in this paper were established from examination of 31 control biopsies, obtained from the same muscle and with the same anaesthesia as the MH patients. The criteria have since been changed to those presented elsewhere in this issue. In our laboratories the halothane test (exposure to 0.5-2% halothane) was the more sensitive: 88% of MHS patients reacted to it. The caffeine test was positive in 68% of MHS patients, 0.5-2.0 mmol litre-1 solutions being the most discriminating. Forty-two percent of MHS patients reacted to only one test. Fulminant MH was the most common reason for investigation; all these families contained MHS members. Masseter spasm occurred as sole sign in 21 families, of which 11 were MHS. Only 10% of MHS patients had other signs or symptoms of neuromuscular disease such as muscle cramps or muscular dystrophy. Three families had experienced sudden infant death syndrome (SIDS), and two teenage brothers in a MHS family died suddenly, but death was unrelated to anaesthesia.

Malignant hyperthermia in a myopathic child. Prolonged postoperative course requiring dantrolene.

An 18-month-old boy with congenital muscular dystrophy began to develop clear signs of the malignant hyperthermia syndrome after 85 min of halothane/nitrous oxide anaesthesia. Dantrolene, 2 mg/kg i.v., was immediately effective, but temperature, heart rate and carbon dioxide production were all increased for 2 days postoperatively in spite of repeated dantrolene administration.

Malignant hyperthermia syndrome in an anxious patient.

A 30-yr-old patient with fulminant ulcerative colitis was anaesthetized on three occasions, for colectomy and rectal stump removal. The first anaesthesia, with droperidol and fentanyl and pancuronium neuromuscular block, was uneventful. Addition of suxamethonium on the second occasion and use of the original drugs plus nitrous oxide for the third anaesthesia produced symptoms of MH, which was confirmed by muscle biopsy. There was no hyperthermia. The patient's admitted anxiety before the last two operations is believed to have played a role in the genesis of MH.

Beta2-adrenergic stimulation of thyroid hormone secretion.

The influence on thyroid hormone secretion of the nonselective beta-adrenergic stimulant isoproterenol (IPNE), of a selective beta1-adrenergic stimulant, 1-isopropylamino-3-(2-thiazoloxy)-2-propanol (ITP), and of a selective beta2-adrenergic stimulant, terbutaline, was investigated in mice. A combination of light microscopy (colloid droplet formation) and bioassay (blood radioiodine--BRI--measurements) was used. IPNE and terbutaline induced formation of colloid droplets and increased BRI levels, whereas ITP was ineffective. The responses to IPNE and terbutaline were abolished or reduced by pretreatment with L-propranolol, but were not inhibited for pretreatment with D-propranolol or phentolamine. The results indicate that secretion of thyroid hormone can be induced through the mediation of beta2-adrenergic receptors.