Rewarming following hypothermic cardiopulmonary bypass in the malignant hyperthermia-susceptible patient: implications for diagnosis and perioperative management.

A 55-year-old, malignant hyperthermia-susceptible patient underwent myocardial revascularization without incident. Six hours postoperatively, he developed what was initially diagnosed as an MH crisis, for which he received intravenous dantrolene. The resultant muscle weakness prolonged the duration of postoperative mechanical ventilation and likely contributed to the development of a postoperative pneumonia. Plasma dantrolene levels were measured for the first 48 hours postoperatively and correlated with clinical findings. On reviewing the patient's perioperative course, it was felt that the hypermetabolic state was not due to MH. The patient's pattern of rewarming following hypothermic cardiopulmonary bypass was similar to non-MH-susceptible patients. Because of the difficulty in diagnosing a MH crisis after hypothermic bypass, it is recommended that patients receive prophylactic dantrolene preoperatively and after bypass. Nondepolarizing muscle relaxants should be given postoperatively to prevent shivering and respiratory acidosis while patients rewarm.

Plasma levels of dantrolene following oral administration in malignant hyperthermia-susceptible patients.

Reports of the lack of protection following oral dantrolene prophylaxis have led some authors to recommend only intravenous administration of dantrolene for prophylaxis against malignant hyperthermia at induction of anesthesia. The authors determined whether a specific regimen of preoperative oral dantrolene would result in protective blood levels at induction of anesthesia, and in the postoperative period. Ten malignant hyperthermia-susceptible (MHS) patients were given a total dose of 5 mg.kg-1 of oral dantrolene in three or four divided doses, every 6 h, with the last dose 4 h preoperatively. Plasma dantrolene levels were determined by reverse phase high pressure liquid chromatography at induction of anesthesia and every 6 h thereafter for 48 h. All ten patients had plasma dantrolene levels over 2.8 micrograms.ml-1 at induction of anesthesia, for at least 6 h and, in three patients, up to 18 h after induction. Every patient had an uneventful perioperative course. Side effects (drowsiness, weakness) occurred in seven patients. An elimination half-life of 15.8 +/- 6.0 h was determined. In contrast to intravenous dantrolene, this specific oral dantrolene regimen resulted in protective plasma levels for 6-18 h after induction of anesthesia. These results were likely due to the relatively high bioavailability of oral dantrolene and, possibly, to continued absorption of dantrolene in the postoperative period.

Oxygenation during high-frequency ventilation compared with conventional mechanical ventilation in two models of lung injury.

Oxygenation and mean lung volume were investigated during high frequency oscillation (HFO) and conventional mechanical ventilation (CMV) in two models of lung disease and related to the lung mechanics of the lesions. Oleic acid (n = 10) or lung lavage (n = 12) pulmonary injury was induced in a series of rabbits. Each animal was alternately ventilated with HFO (15 Hz sinusoidal wave form) and CMV (flow generator I:E, 1:2; f, 30 breaths/min; VT, 10 to 15 ml/kg) at matched mean airway pressure. Pao2 was measured 5 minutes after onset of ventilation. In the lung lavage model Pao2 was significantly greater during HFO than CMV (Pao2 228 +/- 116 torr vs 71 +/- 42 torr) provided that mean airway pressure was greater than the distinct opening pressure characteristic of this lesion. In the oleic acid model oxygenation was again superior during HFO (Pao2 269 +/- 116 torr vs 110 +/- 83 torr), but only if HFO was preceded by a sustained inflation. Plethysmography in a subset of six rabbits from each group revealed that the improvements in oxygenation were associated with significantly higher mean lung volumes during HFO than CMV (58 +/- 30 ml vs 29 +/- 14 ml lung lavage model, 45 +/- 15 ml vs 30.9 +/- 13 ml on the oleic acid model). The importance of a sustained inflation in rapidly optimizing gas exchange during HFO but not CMV was demonstrated. A sustained inflation resulted in immediate and sustained increases in Pao2 (from 134 +/- 102 torr to 274 +/0 124 torr in the oleic acid model; from 115 +/- 105 torr to 291 +/- 143 torr in the lung lavage model) and mean lung volume (41.8 +/- 11 to 53.8 +/- 9.7 ml in the oleic acid model, 30.9 +/- 7.7 ml to 42.8 +/- 5 ml in the lung lavage model). It is suggested that in these two particular models of lung disease, HFO, when combined with a sustained inflation (to provide opening forces), can more fully exploit the pressure volume hysteresis of unstable lung units than CMV, thereby resulting in the larger mean lung volumes and better oxygenation observed during HFO.