Early post-operative vasoplegia in lung transplantation

Abstract

Introduction Lung transplantation (LTx) is the main treatment for end-stage respiratory failure. The post-operative development of pulmonary and systemic inflammation represents a severe limitation leading to Primary Graft Dysfunction (PGD) and multi-organ failure with great impact on survival and clinical outcomes. We hypothesise that LTx is associated with a high incidence of vasoplegia and that this is associated with a profound inflammatory response and high mortality and organ dysfunction. To test our hypotheses, we have identified patients who developed vasoplegia in the first 48 hours after LTx, described the impact of the vasoplegia on the clinical impact and explored the role of neutrophil degranulation products, such as Myeloperoxidase (MPO) and Heparin Binding Protein (HBP). Methods We recruited 40 patients who underwent LTx in 2013-15 at Harefield Hospital. Clinical data were recorded. Vasoplegia was defined according to Tsiouris et al (1). PGD was diagnosed and scored according to ISHLT criteria 2005, Acute Kidney Injury (AKI) to KDIGO criteria. Blood samples were collected before surgery and at different time-points after the arrival in ITU and analysed for MPO and HBP levels (Axis-Shield Heparin Binding Protein EIA, Abcam MPO ELISA kit). Data were analysed and reported as appropriate. Results 13 patients developed post-operative vasoplegia (32%). Within this group, 6 patients also developed PGD 3 (46%, p 0.284) and 9 AKI (69%, p 0.312), 7 requiring haemofiltration (54%, p 0.032). Vasoplegic patients showed lower P/F ratios on day 1 (23.1 [17.3, 35.7] vs. 31.4 [24.4, 41.4], p 0.151), day 2 936.0 [29.0, 44.6] vs. 46.7 [41.4, 50.5], p 0.011), and day 3 939.6 [29.7, 46.9] vs. 48.3 [43.4, 53.2], p 0.004). They also had longer ventilation duration (159 [59, 971] hours vs. 29 [15, 114] hours, p 0.012) and longer ITU stay (22 [5, 43] days vs. 5 [3, 9] days, p 0.029). Overall survival was not significantly affected by vasoplegia (log rank 1.005 p 0.316). Vasoplegic patients exhibit a tendency for higher levels of MPO early after surgery (232 [140, 406] ng/ml vs. 170 [110, 336] ng/ml before surgery (p 0.247), 566 [84, 1246] ng/ml vs. 312 [121, 658] ng/ml at the arrival in ITU (p 0.504), 441 [231, 753] ng/ml vs. 300 [142, 518] ng/ml at 6 hours (p 0.353), 160 [52, 447] ng/ml vs. 139 [112, 744] ng/ml at 12 hours (p 0.200)), but similar levels of HBP. Discussion These results identify high incidence of vasoplegia in the LTx population. One third of our patients developed vasoplegia in the early post-operative period with significant impact on the early post-operative function in terms of gas exchange and need for ventilatory support and level 3 care. Moreover, the data may suggest potential involvement of neutrophil-derived myeloperoxidase and, therefore oxidative stress, in the early postoperative period events.