Cardiopulmonary bypass and recombinant plasminogen activator for treatment of experimental fatal pulmonary embolism

Introduction

Treatment of acute pulmonary embolism (PE), which causes life-threatening cardiovascular collapse, consists of cardiopulmonary bypass (CPB) and surgical embolectomy. In the clinical practice we have treated three such patients successfully with CPB but instead of performing embolectomy, administered recombinant plasminogen activator (rt-PA). We studied the circulatory and respiratory effects of this combined therapy in a swine model of fatal PE.

Methods

Seven pigs (90 kg) were i.v. anesthetized, muscle relaxed, tracheally intubated and mechanically ventilated (FiO₂ 1.0). A large-bore catheter (8.5 mm ID) was inserted in the right superior vena cava (for injection of preformed blood clots) and large-bore catheters were inserted in the inferior vena cava via the femoral vein and in the aorta via the femoral artery (for accessing CPB). We measured the mean arterial pressure (MAP), cardiac output (CO), blood gases, pulmonary artery pressure measurement (MPAP), end-tidal CO₂ (ETCO₂) and blood gases. Then 100–300 ml preformed blood clot was injected until systemic circulation ceased (systolic AP < 25 mmHg) and a 5 minute interval was allowed before start of CPB (flow rate of 4–7 l/min). Heparin 10,000 IE was given i.v., and rt-PA 10 mg as an i.v. bolus followed by an i.v. infusion of 90 mg during 2 hours. If ventricular fibrillation occurred, cardioversion was performed. After 145 minutes CPB was weaned off, and after a further 40 minutes the experiment was ended.

Results

Five animals developed ventricular fibrillation, while one animal maintained sinus rhythm. After 2 hours all animals had an atrial rhythm. All animals were weaned off CPB and survived until the experiment ended. Values before and after CPB (median and range): MAP (mmHg) 101 (86, 109) and 75 (46, 106); CO (l/min) 6.7 (4.3, 11) and 6.2 (3.6, 7.8); MPAP (mmHg) 22 (19, 36) and 44 (31, 82) (P < 0.05); ETCO₂ (kPa) 5.6 (4.3, 6.5) and 2.7 (2.4, 3.4) (P < 0.05); PaCO₂ (kPa) 6.2 (5.2, 7.2) and 6.1 (4.8, 7.3); PaO₂ (kPa) 60 (50, 68) and 55 (30, 64).

Conclusion

Although there were signs – that is, lower ETCO₂ and higher MPAP – that the massive clots were not fully dissolved after 185 minutes, this study shows that fatal PE might be treated effectively with CPB combined with simultaneous thrombolytic therapy.