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Comparative analysis of in vitro contracture tests with ryanodine and a combination of ryanodine with either halothane or caffeine: a comparative investigation in malignant hyperthermia.
Acta Anaesthesiol Scand. 2004 Sep; 48(8):1019-27.AA

Abstract

BACKGROUND

The diagnosis of susceptibility to malignant hyperthermia (MH) is currently performed on muscle biopsies subjected to halothane-caffeine in vitro contracture tests (IVCTs). There is a consensus on our need to improve the diagnostic potential of IVCTs if we are to maximize the information available for research and diagnosis in MH. This study was designed as a pilot comparative study and we aimed at comparing the ryanodine test and new tests using a combination of ryanodine, halothane and caffeine.

METHODS

One hundred and thirty-two subjects (52 MHS and 80 MHN) were included in this study and new IVCTs were performed in additional muscle biopsy specimens. The contracture time-course was compared considering the onset time of contracture (OT) and the time to reach a 10 mN contracture (10T). Cut-off values were determined using ROC analyses.

RESULTS

For the ryanodine test, sensitivity and specificity calculated for OT were 84.6% and 90.4%, respectively, and were better than those obtained using 10T. Combined tests using either caffeine and ryanodine or halothane and ryanodine did provide higher sensitivities (from 85.3 to 93.9%). A better specificity was only observed for the IVC tests combining halothane (cumulated) and caffeine both with ryanodine (93.9% for both). The largest sensitivity was observed when halothane was used as a bolus and combined with ryanodine. The specificity was always larger with the combined tests as compared to the test using ryanodine alone (from 79.1 to 90.9%). This superiority was confirmed, at least in part, when comparing genetic investigations and the results of new tests in a subgroup of subjects.

CONCLUSIONS

This pilot study showed a clear diagnostic potential for new IVC tests combining halothane, the triggering agent of MH, and ryanodine acting at the calcium release channel, and should be considered as a first step in the investigation of combined tests.

Authors+Show Affiliations

Centre de Résonance Magnétique Biologique et Médicale, Faculté de Médecine, Marseille, France. david.bendahan@medecine.university-mrs.frNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Comparative Study
Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

15315621

Citation

Bendahan, D, et al. "Comparative Analysis of in Vitro Contracture Tests With Ryanodine and a Combination of Ryanodine With Either Halothane or Caffeine: a Comparative Investigation in Malignant Hyperthermia." Acta Anaesthesiologica Scandinavica, vol. 48, no. 8, 2004, pp. 1019-27.
Bendahan D, Guis S, Monnier N, et al. Comparative analysis of in vitro contracture tests with ryanodine and a combination of ryanodine with either halothane or caffeine: a comparative investigation in malignant hyperthermia. Acta Anaesthesiol Scand. 2004;48(8):1019-27.
Bendahan, D., Guis, S., Monnier, N., Kozak-Ribbens, G., Lunardi, J., Ghattas, B., Mattei, J. P., & Cozzone, P. J. (2004). Comparative analysis of in vitro contracture tests with ryanodine and a combination of ryanodine with either halothane or caffeine: a comparative investigation in malignant hyperthermia. Acta Anaesthesiologica Scandinavica, 48(8), 1019-27.
Bendahan D, et al. Comparative Analysis of in Vitro Contracture Tests With Ryanodine and a Combination of Ryanodine With Either Halothane or Caffeine: a Comparative Investigation in Malignant Hyperthermia. Acta Anaesthesiol Scand. 2004;48(8):1019-27. PubMed PMID: 15315621.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Comparative analysis of in vitro contracture tests with ryanodine and a combination of ryanodine with either halothane or caffeine: a comparative investigation in malignant hyperthermia. AU - Bendahan,D, AU - Guis,S, AU - Monnier,N, AU - Kozak-Ribbens,G, AU - Lunardi,J, AU - Ghattas,B, AU - Mattei,J-P, AU - Cozzone,P J, PY - 2004/8/19/pubmed PY - 2004/12/16/medline PY - 2004/8/19/entrez SP - 1019 EP - 27 JF - Acta anaesthesiologica Scandinavica JO - Acta Anaesthesiol Scand VL - 48 IS - 8 N2 - BACKGROUND: The diagnosis of susceptibility to malignant hyperthermia (MH) is currently performed on muscle biopsies subjected to halothane-caffeine in vitro contracture tests (IVCTs). There is a consensus on our need to improve the diagnostic potential of IVCTs if we are to maximize the information available for research and diagnosis in MH. This study was designed as a pilot comparative study and we aimed at comparing the ryanodine test and new tests using a combination of ryanodine, halothane and caffeine. METHODS: One hundred and thirty-two subjects (52 MHS and 80 MHN) were included in this study and new IVCTs were performed in additional muscle biopsy specimens. The contracture time-course was compared considering the onset time of contracture (OT) and the time to reach a 10 mN contracture (10T). Cut-off values were determined using ROC analyses. RESULTS: For the ryanodine test, sensitivity and specificity calculated for OT were 84.6% and 90.4%, respectively, and were better than those obtained using 10T. Combined tests using either caffeine and ryanodine or halothane and ryanodine did provide higher sensitivities (from 85.3 to 93.9%). A better specificity was only observed for the IVC tests combining halothane (cumulated) and caffeine both with ryanodine (93.9% for both). The largest sensitivity was observed when halothane was used as a bolus and combined with ryanodine. The specificity was always larger with the combined tests as compared to the test using ryanodine alone (from 79.1 to 90.9%). This superiority was confirmed, at least in part, when comparing genetic investigations and the results of new tests in a subgroup of subjects. CONCLUSIONS: This pilot study showed a clear diagnostic potential for new IVC tests combining halothane, the triggering agent of MH, and ryanodine acting at the calcium release channel, and should be considered as a first step in the investigation of combined tests. SN - 0001-5172 UR - https://www.unboundmedicine.com/medline/citation/15315621/Comparative_analysis_of_in_vitro_contracture_tests_with_ryanodine_and_a_combination_of_ryanodine_with_either_halothane_or_caffeine:_a_comparative_investigation_in_malignant_hyperthermia_ L2 - https://doi.org/10.1111/j.0001-5172.2004.00461.x DB - PRIME DP - Unbound Medicine ER -