Efficacy of a Low-Tidal Volume Ventilation Strategy to Prevent Reperfusion Lung Injury after Pulmonary Thromboendarterectomy.

RATIONALE: Reperfusion lung injury is a postoperative complication of pulmonary thromboendarterectomy that can significantly affect morbidity and mortality. Studies in other postoperative patient populations have demonstrated a reduction in acute lung injury with the use of a low-tidal volume (Vt) ventilation strategy. Whether this approach benefits patients undergoing thromboendarterectomy is unknown. OBJECTIVES: We sought to determine if low-Vt ventilation reduces reperfusion lung injury in patients with chronic thromboembolic pulmonary hypertension undergoing thromboendarterectomy. METHODS: Patients undergoing thromboendarterectomy at one center were randomized to receive either low (6 ml/kg predicted body weight) or usual care Vts (10 ml/kg) from the initiation of mechanical ventilation in the operating room through Postoperative Day 3. The primary endpoint was the onset of reperfusion lung injury. Secondary outcomes included severity of hypoxemia, days on mechanical ventilation, and intensive care unit and hospital lengths of stay. MEASUREMENTS AND MAIN RESULTS: A total of 128 patients were enrolled and included in the analysis; 63 were randomized to the low-Vt group and 65 were randomized to the usual care group. There was no statistically significant difference in the incidence of reperfusion lung injury between groups (32%, n=20 in the low-Vt group vs. 23%, n=15 in the usual care group; P=0.367). Although differences were noted in plateau pressures (17.9 cm H2O vs. 20.1 cm H2O, P<0.001) and peak inspiratory pressures (20.4 cm H2O vs. 23.0 cm H2O, P<0.001) between the low-Vt and usual care groups, respectively, mean airway pressures, PaO2/FiO2, days on mechanical ventilation, and ICU and hospital lengths of stay were all similar between groups. CONCLUSIONS: In patients with chronic thromboembolic pulmonary hypertension undergoing pulmonary thromboendarterectomy, intra- and postoperative ventilation using low Vts (6 mg/kg) compared with usual care Vts (10 mg/kg) does not reduce the incidence of reperfusion lung injury or improve clinical outcomes. Clinical trial registered with www.clinicaltrials.gov (NCT00747045).

S-nitrosoglutathione preserves platelet function during in vitro ventricular assist device circulation.

Complications (severe bleeding/thromboembolism) may occur during ventricular assist device (VAD) circulation, caused mainly by platelet dysfunction from platelet activation. We hypothesized that S-nitrosoglutathione (GSNO), having platelet activity preservation properties like nitric oxide (NO), may be a titratable agent to diminish platelet activation and thus preserve platelet function. Dose-response measurement of platelet aggregation by GSNO was performed using an aggregometer. GSNO (1,000 microM) caused inhibition of collagen and ristocetin induced aggregation by approximately 50%. Next, in vitro ventricular assist device (VAD) circulation was performed (over 48 hours using human whole blood), both without (control) and with GSNO (1,000 microM), and the aggregability of perfusate was measured at 0, 0.5, 1, 3, 6, 12, 24, and 48 hours. In control VAD circuits, collagen induced platelet aggregability gradually decreased and became significantly lower after 3 hours of circulation. With GSNO, platelet function did not significantly decrease until after 12 hours. Similar results were seen for ristocetin induced aggregation; control aggregation dropped significantly after 6 hours, but not until after 24 hours with GSNO. Liquid phase measurement of total nitrogen oxides (NO(T)) confirmed added GSNO maintained high perfusate NO(T) compared with control. GSNO is effective in preserving platelet aggregation during the first 12 to 24 hours in vitro and may be effective in preserving platelet function by inhibiting platelet activation during in vivo VAD circulation.