A modified perfusion protocol for pulmonary endarterectomy in a patient with a hematologic malignancy treated with a tyrosine kinase inhibitor.

Tyrosine kinase inhibitors (TKI) are known to be highly effective in the treatment of various cancers with kinase-domain mutations such as chronic myelogenous leukemia. However, they have important side effects such as increased vascular permeability and pulmonary hypertension. In patients undergoing pulmonary endarterectomy with deep hypothermic circulatory arrest, these side effects may exacerbate postoperative complications such as reperfusion edema and persistent pulmonary hypertension. We report on a simple modification of the perfusion strategy to increase intravascular oncotic pressure by retrograde autologous priming and the addition of packed cells and albumin in a patient treated with a TKI.

Anticoagulation management during pulmonary endarterectomy with cardiopulmonary bypass and deep hypothermic circulatory arrest.

INTRODUCTION: Pulmonary endarterectomy requires cardiopulmonary bypass and deep hypothermic circulatory arrest, which may prolong the activated clotting time. We investigated whether activated clotting time-guided anticoagulation under these circumstances suppresses hemostatic activation. METHODS: Individual heparin sensitivity was determined by the heparin dose-response test, and anticoagulation was monitored by the activated clotting time and heparin concentration. Perioperative hemostasis was evaluated by thromboelastometry, platelet aggregation, and several plasma coagulation markers. RESULTS: Eighteen patients were included in this study. During cooling, tube-based activated clotting time increased from 719 (95% confidence interval = 566-872 seconds) to 1,273 (95% confidence interval = 1,136-1,410 seconds; p < 0.01) and the cartridge-based activated clotting time increased from 693 (95% confidence interval = 590-796 seconds) to 883 (95% confidence interval = 806-960 seconds; p < 0.01), while thrombin-antithrombin showed an eightfold increase. The heparin concentration showed a slightly declining trend during cardiopulmonary bypass. After protamine administration (protamine-to-heparin bolus ratio of 0.82 (0.71-0.90)), more than half of the patients showed an intrinsically activated coagulation test and intrinsically activated coagulation test without heparin effect clotting time >240 seconds. Platelet aggregation through activation of the P2Y12 (adenosine diphosphate test) and thrombin receptor (thrombin receptor activating peptide-6 test) decreased (both -33%) and PF4 levels almost doubled (from 48 (95% confidence interval = 42-53 ng/mL) to 77 (95% confidence interval = 71-82 ng/mL); p < 0.01) between weaning from cardiopulmonary bypass and 3 minutes after protamine administration. CONCLUSION: This study shows a wide variation in individual heparin sensitivity in patients undergoing pulmonary endarterectomy with deep hypothermic circulatory arrest. Although activated clotting time-guided anticoagulation management may underestimate the level of anticoagulation and consequently result in a less profound inhibition of hemostatic activation, this study lacked power to detect adverse outcomes.

Goal-directed perfusion to reduce acute kidney injury: A randomized trial.

OBJECTIVE: To determine whether a goal-directed perfusion (GDP) strategy aimed at maintaining oxygen delivery (DO2) at ≥280 mL·min-1·m-2 reduces the incidence of acute kidney injury (AKI). METHODS: This multicenter randomized trial enrolled a total of 350 patients undergoing cardiac surgery in 9 institutions. Patients were randomized to receive either GDP or conventional perfusion. A total of 326 patients completed the study and were analyzed. Patients in the treatment arm were treated with a GDP strategy during cardiopulmonary bypass (CPB) aimed to maintain DO2 at ≥280 mL·min-1·m-2. The perfusion strategy for patients in the control arm was factored on body surface area and temperature. The primary endpoint was the rate of AKI. Secondary endpoints were intensive care unit length of stay, major morbidity, red blood cell transfusions, and operative mortality. RESULTS: Acute Kidney Injury Network (AKIN) stage 1 was reduced in patients treated with GDP (relative risk [RR], 0.45; 95% confidence interval [CI], 0.25-0.83; P = .01). AKIN stage 2-3 did not differ between the 2 study arms (RR, 1.66; 95% CI, 0.46-6.0; P = .528). There were no significant differences in secondary outcomes. In a prespecified analysis of patients with a CPB time between 1 and 3 hours, the differences in favor of the treatment arm were more pronounced, with an RR for AKI of 0.49 (95% CI, 0.27-0.89; P = .017). CONCLUSIONS: A GDP strategy is effective in reducing AKIN stage 1 AKI. Further studies are needed to define perfusion interventions that may reduce more severe levels of renal injury (AKIN stage 2 or 3).