British Journal of Anaesthesia, Vol 80, Issue 3 389-394, Copyright © 1998 by The Board of Management and Trustees of the British Journal of Anaesthesia
P. M. Hopkins, E. Hartung, F. Wappler and Group. The European Malignant Hyperthermia
A common protocol for in vitro contracture testing using the plant alkaloid
ryanodine has been used by the European Malignant Hyperthermia Group since
1993. This protocol describes a test using I mumol/litre of high purity
ryanodine (98%) added as a single bolus dose. The main aim of this study
was to compare the results obtained with this test between laboratories
with a view to assessing the validity of adopting common diagnostic
end-points for use in future collaborative studies. In order to do this it
was first necessary to determine the optimum cut- off values of the
end-points for discriminating between patients diagnosed as susceptible or
not to malignant hyperthermia. The end- points under evaluation were
expressed in terms of time after application of ryanodine at which a
certain degree of contracture develops. In this study, four end-points were
investigated: time to initial contracture development (Ot); time to
development of a 10-mN contracture (10t); time from addition of ryanodine
to when baseline tension exceeds pre-drug tension (0tp); and time for
contracture to reach 10 mN above pre-drug baseline tension (10tp). This
protocol was developed initially and used by three investigating centres
and the initial assessment of the end-points and their discriminatory
ability was made using the first 100 patients from each of centres 1 and 2,
and the first 90 patients from centre No. 3. Optimal cut-off values for
each of the end-points were determined using logistic regression analysis.
Discriminatory ability was improved by combining the Ot and 10t end-points
(P < 0.05) but not significantly by combining the 0tp and 10tp
end-points. Both methods of categorization were highly sensitive and
specific compared with the current standard diagnostic tests. Results from
eight additional diagnostic centres which have used the ryanodine
contracture test more recently, while indicating that susceptible and
normal individuals can be distinguished within a single laboratory,
produced a level of variability between testing centres for the ryanodine
contracture test that is incompatible with the use of common cut-off
values. Possible causes for this variability between laboratories are
discussed.
COMMENTARY
Multicentre evaluation of ryanodine contracture testing in malignant hyperthermia
Academic Unit of Anaesthesia, St James's University Hospital, Leeds LS9 7TF; University of Wurzburg, Germany; University of Hamburg, Germany
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