Transient perioperative inflammation following lung transplantation and major thoracic surgery with elective extracorporeal support: a prospective observational study

Abstract

Background: The clinical relevance of inflammation induced by elective perioperative extracorporeal membrane oxygenation (ECMO) usage as an integral part of modern lung transplantation (LUTX) remains elusive. The aim of this study was to determine the perioperative cytokine response accompanying major thoracic surgery employing different extracorporeal devices comprising ECMO, cardiopulmonary bypass (CPB), or no extracorporeal circulation in relation to inflammation, clinically tangible as increased sequential organ failure assessment (SOFA) score, called SOFA. Methods: In this prospective, observational pilot study 42 consecutive patients with end-stage pulmonary disease undergoing LUTX; 15 patients with chronic thromboembolic pulmonary hypertension (CTEPH) undergoing pulmonary endarterectomy and 15 patients with lung cancer undergoing major lung resections were analysed. Cytokine serum concentrations and SOFA were determined before, at end of surgery and in the following postoperative days. Results: LUTX on ECMO and pulmonary endarterectomy (PEA) on CPB triggered an immediate increase in cytokine serum concentrations at end of surgery: IL-6: 66-fold and 71-fold, IL-10: 3-fold and 2.5-fold, ST2/IL-33R: 5-fold and 4-fold and SOFA: 10.5±2.8 and 10.7±1.7, that decreased sharply to baseline levels from postoperative day 1-5. Despite low perioperative mortality (3 patients, 4.1%) extremely high SOFA ≥13 was associated with mortality after LUTX. Delta-SOFA distinguished survivors from nonsurvivors: −4.5±3.2 vs. −0.3±1.5 (P=0.001). Increased IL-6 serum concentrations were predictive for increased SOFA (sensitivity: 97%, specificity: 80%). Peak cytokine serum concentrations correlated with ECC duration, maximal lactate, transfusion of red-blood-cells, fresh-frozen-plasma, and catecholamine support.Conclusions: LUTX and PEA on extracorporeal circulation with an excellent outcome triggered an immediate rise and concomitant fall of inflammation as observed in cytokine serum concentrations and SOFA. High absolute SOFA in the presence of an uncomplicated postoperative course may pertain to specific management strategies rather than organ failure.

Follistatin-like 1 and Biomarkers of Neutrophil Activation Are Associated with Poor Short-Term Outcome after Lung Transplantation on VA-ECMO

“…In this study we also observed a strong association between elevated CCL4 serum concentrations and a high SOFA score. As previously reported by our study group, IL-6 was a highly sensitive marker for the detection of patients with high SOFA scores [ 23 ]. IL-6 is known as a sensitive mediator of the acute phase reaction and is frequently determined to detect inflammatory conditions in the clinical routine [ 45 ].…”

“…Five patients needed renal replacement therapy. Furthermore, two patients died within 30 days after LuTX [ 23 ].…”

“…An initial dose of 60 IU/kg of heparin was administered prior to initiation of intraoperative VA-ECMO. Patients were kept normothermic throughout the entire surgical procedure [ 23 ].…”

“…The assessment of the neurological function using the Glasgow coma scale (GCS) was excluded due to limited evaluability in actively sedated patients. The following data was collected: need for mechanical ventilation, PaO 2 /FiO 2 ratio, platelet count, bilirubin, mean arterial pressure, doses of adrenergic agents, creatinine, and urine output [ 23 , 28 ].…”

Peri-Operative Changes of Inflammatory Markers and Their Implications in Pulmonary Endarterectomy

“…Blood exposure to CPB circuits leads to the systemic inflammatory response, leukocyte activation, and the release of pro-inflammatory and anti-inflammatory cytokines [39], ultimately causing multiorgan function failure. The CPB of PEA surgery was performed with a non-pulsatile flow [40]. Studies have shown that non-pulsatile perfusion causes a decrease in hemodynamic energy, resulting in capillary collapse, microvascular shunting, and the activation of inflammatory mediators [40,41].…”