Clinical evaluation of Duraflo II heparin treated extracorporeal circulation circuits (2nd version). The European Working Group on heparin coated extracorporeal circulation circuits.

OBJECTIVES: To evaluate whether the application of heparin treated circuits for elective coronary artery surgery improves postoperative recovery, a European multicenter randomised clinical trial was carried out. METHODS: In 11 European heart centers, 805 low-risk patients underwent cardiopulmonary bypass (CPB) with either an untreated circuit (n = 407) or an identical but heparin treated circuit (n = 398, Duraflo II). RESULTS: Significant differences were found among participating centers with respect to patient characteristics, blood handling procedures and postoperative care. The use of heparin treated circuits revealed no overall changes in blood loss, blood use, time on ventilator, occurrence of adverse events, morbidity, mortality, and intensive care stay. These results did not change after adjustment for centers and (other) prognostic factors as analysed with logistic regression. In both groups no clinical or technical (patient or device related) side effects were reported. Because female gender and aortic cross clamp time appeared as prognostic factors in the logistic regression analysis, a subgroup analysis with these variables was performed. In a subpopulation of females (n = 99), those receiving heparin treated circuits needed less blood products, had a lower incidence of rhythm disturbances and were extubated earlier than controls. In another subgroup of patients with aortic cross clamp time exceeding 60 min (n = 197), the amount of patients requiring prolonged intensive care treatment (> 24 h) was significantly lower when they received heparin treated circuits versus controls. CONCLUSION: These findings suggest that improved recovery can be expected with heparin treated circuits in specific higher risk patient populations (e.g. females) and when prolonged aortic cross clamp time is anticipated. Further investigations are recommended to analyses the clinical benefit of heparin treated circuits in studies with patients in different well defined risk categories and under better standardised circumstances.

Digoxin enhances bupivacaine toxicity in rats.

The influence of digoxin on the systemic toxic effects of bupivacaine was studied in a rodent animal model. The experiment was undertaken with consideration to clinical situations such as pregnancy that are associated with the secretion of an endogenous digoxin-like factor. Twenty Wistar male rats, under barbiturate anesthesia and controlled ventilation, received either 5 micrograms/kg intravenous digoxin (n = 10) or saline (n = 10), blinded to the observer. Digoxin serum concentration was 1.8 +/- 0.24 ng/ml in the study group. Thirty minutes after digoxin or saline was administered, bupivacaine was infused at a constant rate of 2mg/kg/minute. The threshold doses of bupivacaine toxic effects (first ventricular arrhythmia, 25% fall of baseline heart rate, 25% fall of baseline mean arterial blood pressure, first seizure activity, isoelectric electroencephalogram, and asystole) were significantly lower in the digoxin group, as were the lethal bupivacaine serum concentrations. Digoxin, in hyperoxic nonacidotic rats, increases the cardiac and central nervous system toxicity of bupivacaine. Based on the known electrophysiologic actions of these two drugs, a synergistic toxic interaction is demonstrated.