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 non-survivors: -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.

Keywords: Extracorporeal membrane oxygenation (ECMO); lung transplantation (LUTX); perioperative inflammation; pulmonary endarterectomy (PEA); sequential organ failure assessment (SOFA).

Figure 1

Increased cytokine expression after LUTX and PEA were depicted as fold increase (increase from baseline prior to surgery to ICU admission). Serum cytokine expressions including IL-6 (A), IL-10 (B) and ST2/IL33 (C) of patients undergoing LUTX with ECMO and PEA with CPB; and patients undergoing lung resection without ECC were depicted. A statistically significant increase in IL- 10 serum concentrations among patients undergoing LUTX with CF and IPAH compared to COPD patients from baseline prior to surgery to peak concentrations after surgery were shown in (D). Significantly increased IL-10 serum concentrations from baseline to end of surgery in patients undergoing primary LUTX compared to patients undergoing Re-LUTX are presented in (E). LUTX, lung transplantation; PEA, pulmonary endarterectomy; ECMO, extracorporeal membrane oxygenation; ECC, extracorporeal circulation; COPD, chronic obstructive pulmonary disease; LUTX, lung transplantation.

Figure 2

Dynamic cytokine-expression in the perioperative period. The dynamic perioperative cytokine release is shown in IL-6 (A), IL-10 (B), ST2/IL33 (C) and TNF-α (D).

Figure 3

Relative changes in SOFA (Δ-SOFA) in the early postoperative period. A decrease from end of surgery to POD3 of Δ-SOFA in patients admitted to ICU was depicted according to the underlying end stage pulmonary disease COPD, CF, IPF, IPAH and CTEPH patients (A). The postoperative course of the single factors of Δ-SOFA are shown in (B). The postoperative Δ-SOFA of 30-d mortality, patients requiring HF, patients who were reintubated, patients requiring surgical revision and patients with an uneventful postoperative course are shown in (C).