In vitro contracture test for diagnosis of malignant hyperthermia following the protocol of the European MH Group: results of testing patients surviving fulminant MH and unrelated low-risk subjects. The European Malignant Hyperthermia Group.
BACKGROUND
Determination of sensitivity and specificity of the in vitro contracture test (IVCT) for malignant hyperthermia (MH) susceptibility using the European MH Group (EMHG) protocol has been performed in some laboratories but only on a small sample from the combined EMHG. Thus, the purpose of the present study was to determine combined EMHG sensitivity and specificity of the test.


METHODS
Results of IVCT of patients with previous fulminant MH and normal, low-risk subjects (controls) were collected from 22 centres of the EMHG. IVCT was performed according to the EMHG protocol. Patients were included in the study if the clinical crisis had a score of at least 50 points with the Clinical Grading Scale. Low-risk subjects were included provided they did not belong to a family with known MH susceptibility, they had not developed any signs of MH at previous anaesthetics, and they did not suffer from any neuromuscular disease. For inclusion of both MH patients and low-risk subjects, at least 1 muscle bundle in the IVCT should have twitches of 10 mN (1 g) or more. For evaluation of individual tests, only muscle bundles with twitch heights of 10 mN (1 g) or more were used.


RESULTS
A total of 1502 probands had undergone IVCT because of a previous anaesthesia with symptoms and signs suggestive of MH. Of these, 119 had clinical scores of 50 and above. From these 119 MH-suspected patients and from 202 low-risk subjects, IVCT data were collected. Subsequently, 14 MH-suspected patients were excluded from further analysis for the following reasons: In 3 patients, the suspected MH episode could be fully explained by diseases other than MH; in 11 MHS patients, IVCT was incomplete (n = 1), data were lost (n = 3), or none of the muscle bundles fulfilled twitch criteria (n = 7). Of the remaining 105 MH-suspected patients, 89 were MHS, 10 MHEh, 5 MHEc, and one MHN. Thus, we observed a diagnostic sensitivity of the IVCT of 99.0% if the MHE group is considered susceptible (95% confidence interval 94.8-100.0%). Of the 202 low-risk subjects, 3 were MHS, 5 MHEh, 5 MHEc, and 189 MHN. This gives a specificity of the IVCT of 93.6% (95% confidence interval 89.2-96.5%).


CONCLUSIONS
The IVCT for diagnosis of MH susceptibility in Europe has a high sensitivity and a satisfactory specificity.
Ording
H
H
Academic Unit of Anaesthesia, University of Leeds, St. James's University Hospital, UK.
Brancadoro
V
V
Cozzolino
S
S
Ellis
F R
FR
Glauber
V
V
Gonano
E F
EF
Halsall
P J
PJ
Hartung
E
E
Heffron
J J
JJ
Heytens
L
L
Kozak-Ribbens
G
G
Kress
H
H
Krivosic-Horber
R
R
Lehmann-Horn
F
F
Mortier
W
W
Nivoche
Y
Y
Ranklev-Twetman
E
E
Sigurdsson
S
S
Snoeck
M
M
Stieglitz
P
P
Tegazzin
V
V
Urwyler
A
A
Wappler
F
F
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000758:Anesthesia / Q000009:adverse effects; D001706:Biopsy; D002110:Caffeine; D002648:Child; D002675:Child, Preschool; D005260:Female; D006221:Halothane; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D008305:Malignant Hyperthermia / Q000175:diagnosis*; D008875:Middle Aged; D009119:Muscle Contraction / Q000187:drug effects*; D012307:Risk Factors; D012680:Sensitivity and Specificity
D002110:Caffeine; D006221:Halothane