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A1922
October 17, 2007
9:00 AM - 11:00 AM
Room Hall D, Area A,
Comparison of Therapeutic Effectiveness of Dantrolene and Ryanodex in Porcine Malignant Hyperthermia
Mark U. Gerbershagen, M.D., Ph.D., M.B.A., Sandra Becker, M.D., Sascha Burmester, M.D., Alexander Starosse, M.D., Frank Wappler, M.D., Ph.D.
Department of Anesthesiology and Intensive Care Medicine, University of Witten-Herdecke, Cologne, Germany
Introduction: Ryanodex is a novel dantrolene formulation, which is approx. 150 times more water solubile than dantrolene. The aim of this study was to compare the therapeutic management and effectiveness of dantrolene and ryanodex in MH susceptible (MHS) swine.

Methods: Ten MHS swine (age 12±1.1 weeks) were divided in a dantrolene group (n=5, body weight 24.5±3.7 kg) and a ryanodex group (n=5, body weight 24.0±4.0 kg). After premedication, a 22 G catheter was placed in an ear vein and anesthesia was induced with fentanyl and propofol. Following endotracheal intubation controlled ventilation was conducted with an O2/N2O mixture (FiO2=0.45). PaCO2 was set between 38-42 mmHg. Anesthesia was maintained by intravenous administration of fentanyl, propofol and flunitrazepam. Monitoring consisted of ECG, pulseoxymetry, capnometry and invasive measurement of blood pressure. Normothermia was achieved by elevated room temperature. After achieving stable conditions (T0), MH was triggered by inhalative halothane administration. To avoid a rapid onset MH-crisis, low concentrations of 0.1 (T1+T2) and 0.15 (T3+T4) Vol% halothane were used for 96 min each. MH-therapy was initiated at pH 7.00±0.05 (T5). FiO2 was set to 1.0, respiratory minute volume was doubled and 2 mmol kg-1 sodiumbicarbonate administered. To simulate the administration of the substances for a child weighting approx. 24 kg, dantrolene (5 mg kg-1) or ryanodex (5 mg kg-1) respectively were injected via the venous 22 G cannula. Time needed for establishing an aqueous solution and time needed for injection was measured. After MH-therapy data were monitored every 24 min (T6+T7). Data are shown as mean and standard deviation (t-test, p<0.05).

Results: Course of MH-crises and therapeutic effects were comparable between the groups.[table1]Normalisation of heart rate, blood pressure and lactate were similar (data not shown). Time needed for establishing an aqueous solution was significantly shorter for 5 mg kg-1 ryanodex (50.6±8.5 sec) compared to dantrolene (860.3±201.8 sec). Likewise injection time of ryanodex (4.2±1.7 sec) was significantly shorter than of dantrolene (471.5±50.5 sec).

Conclusion: Therapeutic action of ryanodex is comparable to dantrolene. Yet, preparation and administration of the ryanodex solution was faster. Therefore, ryanodex seems to be a promising agent in treatment of MH.

This study was partly supported by the German Research Foundation and by BBraun.

Anesthesiology 2007; 107: A1922
Table 1: Course of pH, pCO2 and temperature during halothane administration and adjacent therapy
artierial pHarterial pCO2temperature
timedantroleneryanodexdantroleneryanodexdantroleneryanodex
T07.46±0.037.46±0.0540.0±1.040.8±1.838.6±0.438.5±0.8
T17.40±0.067.45±0.0644.6±6.143.6±2.438.6±0.538.6±0.6
T27.37±0.097.40±0.0747.8±8.347.8±5.838.6±0.538.6±0.7
T37.32±0.107.36±0.0152.2±10.451.4±8.638.8±0.638.9±1.0
T47.20±0.137.20±0.0865.2±16.269.2±9.239.1±0.639.5±1.6
T56.97±0.057.04±0.07111.0±7.4101.5±5.640.4±0.940.1±0.9
T67.39±0.167.43±0.1745.6±7.347.0±10.840.1±0.840.2±0.5
T77.43±0.047.47±0.0746.4±3.844.8±2.639.8±0.839.9±0.8