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Multicentre evaluation of in vitro contracture testing with bolus administration of 4-chloro-m-cresol for diagnosis of malignant hyperthermia susceptibility

Published online by Cambridge University Press:  11 July 2005

F. Wappler ,
M. Anetseder ,
C. P. Baur ,
K. Censier ,
S. Doetsch ,
P. Felleiter ,
M. Fiege ,
R. Fricker ,
P. J. Halsall  and
E. Hartung
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F. Wappler
Affiliation:
University Hospital Hamburg-Eppendorf, Department of Anaesthesiology, Hamburg, Germany
M. Anetseder
Affiliation:
University of Würzburg, Department of Anaesthesiology, Würzburg, Germany
C. P. Baur
Affiliation:
University of Ulm, Department of Anaesthesiology, Ulm, Germany
K. Censier
Affiliation:
University of Basel, Department of Anaesthesiology, Basel, Switzerland
S. Doetsch
Affiliation:
University of Mainz, Department of Anaesthesiology, Mainz, Germany
P. Felleiter
Affiliation:
University of Vienna, Department of Anaesthesiology and General Intensive Care B, Vienna, Austria
M. Fiege
Affiliation:
University Hospital Hamburg-Eppendorf, Department of Anaesthesiology, Hamburg, Germany
R. Fricker
Affiliation:
University of Vienna, Department of Anaesthesiology and General Intensive Care B, Vienna, Austria
P. J. Halsall
Affiliation:
University of Leeds, Academic Unit of Anaesthesia, Leeds, UK
E. Hartung
Affiliation:
University of Würzburg, Department of Anaesthesiology, Würzburg, Germany Hospital of Stralsund, Department of Anaesthesiology, Stralsund, Germany
J. J. A. Heffron
Affiliation:
University College, Department of Biochemistry, Cork, Ireland
L. Heytens
Affiliation:
University of Antwerp, Department of Intensive Care, Antwerp, Belgium
P. M. Hopkins
Affiliation:
University of Leeds, Academic Unit of Anaesthesia, Leeds, UK
W. Klingler
Affiliation:
University of Ulm, Department of Applied Physiology, Ulm, Germany University of Ulm, Department of Neurology, Ulm, Germany
F. Lehmann-Horn
Affiliation:
University of Ulm, Department of Applied Physiology, Ulm, Germany
Y. Nivoche
Affiliation:
University of Paris, Department of Anaesthesiology, Paris, France
V. Tegazzin
Affiliation:
Traumatic-Orthopaedic Hospital, Department of Anaesthesiology, Padua, Italy
I. Tzanova
Affiliation:
University of Mainz, Department of Anaesthesiology, Mainz, Germany
A. Urwyler
Affiliation:
University of Basel, Department of Anaesthesiology, Basel, Switzerland
R. Weißhorn
Affiliation:
University Hospital Hamburg-Eppendorf, Department of Anaesthesiology, Hamburg, Germany
J. Schulte am Esch
Affiliation:
University Hospital Hamburg-Eppendorf, Department of Anaesthesiology, Hamburg, Germany
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Summary

Background and objective: The in vitro contracture test with halothane and caffeine is the gold standard for the diagnosis of susceptibility to malignant hyperthermia (MH). However, the sensitivity of the in vitro contracture test is between 97 and 99% and its specificity is 78–94% with the consequence that false-negative as well as false-positive test results are possible. 4-Chloro-m-cresol is potentially a more specific test drug for the in vitro contracture test than halothane or caffeine. This multicentre study was designed to investigate whether an in vitro contracture test with bolus administration of 4-chloro-m-cresol can improve the accuracy of the diagnosis of susceptibility to MH.

Methods: Three hundred and fifty-two patients from 11 European MH laboratories participated in the study. The patients were first classified as MH susceptible, MH normal or MH equivocal by the in vitro contracture test according to the European MH protocol. Muscle specimens surplus to diagnostic requirements were used in this study (MH susceptible = 103 viable samples; MH equivocal = 51; MH normal = 204). 4-Chloro-m-cresol was added to achieve a concentration of 75 μmol L−1 in the tissue bath. The in vitro effects on contracture development and muscle twitch were observed for 60 min.

Results: After bolus administration of 4-chloro-m-cresol, 75 μmol L−1, 99 of 103 MH-susceptible specimens developed marked muscle contractures. In contrast, only two of 204 MH-normal specimens showed an insignificant contracture development following 4-chloro-m-cresol. From these results, a sensitivity rate of 96.1% and a specificity rate of 99.0% can be calculated for the in vitro contracture test with bolus administration of 4-chloro-m-cresol 75 μmol L−1. Forty-three patients were diagnosed as MH equivocal, but only specimens from 16 patients developed contractures in response to 4-chloro-m-cresol, indicating susceptibility to MH.

Conclusions: The in vitro contracture test with halothane and caffeine is well standardized in the European and North American test protocols. However, this conventional test method is associated with the risk of false test results. Therefore, an improvement in the diagnosis of MH is needed. Regarding the results from this multicentre study, the use of 4-chloro-m-cresol could increase the reliability of in vitro contracture testing.

Keywords

ANAESTHETICS, INHALATION, halothaneMALIGNANT HYPERTHERMIAMUSCLE, muscle fibresORGANIC CHEMICALS, cresols, phenolsPURINES, caffeine, purinones, xanthines
Type
Original Article
Information
European Journal of Anaesthesiology , Volume 20 , Issue 7 , September 2003 , pp. 528 - 536
Copyright
© 2003 European Society of Anaesthesiology

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