Effect of Propofol on the Malignant Hyperthermia Susceptible Pig Model

Krivosic-Horber, R; Reyfort, H.; Becq, M C; Adnet, P.

doi:10.1093/bja/62.6.691

Cited by 23 publications

(5 citation statements)

References 5 publications

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“…For patients known or suspected of being susceptible, potential triggers must be avoided and alternative methods of anesthesia applied, such as with propofol and xenon. 8,29,57,58,83,99 During a crisis, treatment consists of early administration of dantrolene. 82 This lipid-soluble hydantoin derivative acts by inhibiting the release of calcium from the sarcoplasmic reticulum, therefore inhibiting muscle contractures induced by triggering agents and normalizing myoplasmic calcium concentration.…”

Section: Clinical Featuresmentioning

confidence: 99%

Genetics and pathogenesis of malignant hyperthermia

2000

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Malignant hyperthermia (MH) is a potentially life-threatening event in response to anesthetic triggering agents, with symptoms of sustained uncontrolled skeletal muscle calcium homeostasis resulting in organ and systemic failure. Susceptibility to MH, an autosomal dominant trait, may be associated with congenital myopathies, but in the majority of the cases, no clinical signs of disease are visible outside of anesthesia. For diagnosis, a functional test on skeletal muscle biopsy, the in vitro contracture test (IVCT), is performed. Over 50% of the families show linkage of the IVCT phenotype to the gene encoding the skeletal muscle ryanodine receptor and over 20 mutations therein have been described. At least five other loci have been defined implicating greater genetic heterogeneity than previously assumed, but so far only one further gene encoding the main subunit of the voltage-gated dihydropyridine receptor has a confirmed role in MH. As a result of extensive research on the mechanisms of excitation-contraction coupling and recent functional characterization of several disease-causing mutations in heterologous expression systems, much is known today about the molecular etiology of MH.

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Section: Clinical Featuresmentioning

confidence: 99%

Genetics and pathogenesis of malignant hyperthermia

2000

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“…Previous reports have shown that propofol is safe as a general anaesthetic for MHS patients [4][5][6] . In these studies propofol was examined in MHS animals or humans by measuring general anaesthesia or by examining human muscle contraction.…”

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confidence: 90%

Propofol-Induced Changes in Myoplasmic Calcium Concentrations in Cultured Human Skeletal Muscles from RYR1 Mutation Carriers

Migita

Mukaida

Kawamoto

et al. 2007

Anaesth Intensive Care

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Malignant hyperthermia is a pharmacogenetic disorder caused by autosomal dominant mutations in the ryanodine receptor type 1 gene. Propofol has been reported as a safe anaesthetic for malignant hyperthermia susceptible patients but has not been tested on cultured cells from patients with the ryanodine receptor type 1 mutation. The aim of this study was to determine whether propofol could trigger abnormal calcium fluxes in human myotubes isolated from malignant hyperthermia susceptible patients harbouring the native ryanodine receptor type 1 mutation. Muscle specimens were obtained from the patients to diagnose malignant hyperthermia disposition and the calcium-induced calcium release test and molecular genetic analyses were performed. Using the calcium sensitive probe Fura 2, we determined the 340/380 nm wavelength ratios by measuring alterations in calcium homeostasis in isolated myotubes from cultured skeletal muscle specimens. Two patients, one with ryanodine receptor type 1 R2508C and one with the L4838V mutation had accelerated calcium-induced calcium release rates. The 340/380 nm ratios increased when the propofol concentration exceeded 100 µM. The half-maximal activation concentrations (EC 50) for propofol from patients 1 and 2 were 181.1 and 420.5 µM, respectively. Increases in calcium concentrations in response to propofol dosage were limited to doses at least 100-fold greater than those used in clinical settings. These observations correlate well with clinical observations that propofol does not trigger malignant hyperthermia in susceptible humans.

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“…1992 swine anaesthesia studies, but no details of anaesthetic technique or monitoring were included. 4 We decided to investigate further the response of human MHS muscle in vitro, and the response of human MHS patients to bolus doses of propofol prior to conducting studies on the safety of propofol infusion anaesthesia in MHS individuals.…”

Section: Accepted For Publication January 13 1992mentioning

confidence: 99%

Propofol is a ‘Safe’ Anaesthetic Agent in Malignant Hyperthermia Susceptible Patients

McKenzie

Couchman

Pollock

1992

Anaesth Intensive Care

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In this study we investigated in vitro and in vivo effects of propofol in malignant hyperthermia susceptible (MHS) patients in order to assess the safety of propofol infusion as a non-triggering anaesthetic technique for diagnostic and therapeutic procedures. In vitro, human MHS muscle samples were exposed to propofol and changes in (a) baseline tension and (b) contracture tension on exposure to halothane and caffeine were measured. In vivo, (a) anaesthesia was induced in ten muscle biopsy positive MHS patients with propofol 2.5 mg/kg and (b) anaesthesia was produced in five muscle biopsy positive MHS patients with infusions of propofol up to 10 mg/kg/hr. In vitro, human MHS muscle did not develop contractures with propofol alone. Propofol had no significant effect on contracture development in response to halothane and caffeine. In vivo, no evidence of an MH response was detected following induction or maintenance of anaesthesia with propofol. Our results and literature review are in agreement that propofol is a ‘safe’ induction and maintenance agent in MHS patients. Propofol can be used for muscle biopsy anaesthesia because it does not alter the sensitivity of diagnostic muscle biopsy testing.

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Effect of Propofol on the Malignant Hyperthermia Susceptible Pig Model

Cited by 23 publications

References 5 publications

Genetics and pathogenesis of malignant hyperthermia

Genetics and pathogenesis of malignant hyperthermia

Propofol-Induced Changes in Myoplasmic Calcium Concentrations in Cultured Human Skeletal Muscles from RYR1 Mutation Carriers

Propofol is a ‘Safe’ Anaesthetic Agent in Malignant Hyperthermia Susceptible Patients

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