Taking a Big Breath: Identifying and Preventing Pulmonary Complications After Liver Transplantation

In this issue of Transplantation, Oh et al1 describe the results of a retrospective study of postoperative pulmonary complications (PPCs) in 608 patients who underwent living donor liver transplantation over a period of 9 y. More than half of the patients developed pulmonary complications defined as respiratory failure, pneumonia, pulmonary edema, moderate-severe atelectasis, or pleural effusions within 7 d after the transplant. The authors found that a large number of intraoperative variables were associated with PPC including (not surprisingly) Model for End-stage Liver Disease score, ventilator driving pressures, positive end-expiratory pressure (PEEP) and compliance, fluid and blood administration, and duration of anesthesia. However, when using a multivariate analysis and focusing on intraoperative factors, greater driving pressure, and albumin levels at the end of surgery, prolonged hypotension and larger tidal volumes (but not PEEP) remained independently associated with PPC. Patient with PPCs had worse outcomes such as longer intensive care unit stay and worse graft and patient survival. This is the first, larger study of PPC after liver transplantation that investigates the effect of intraoperative variables and therefore factors that may be modifiable. Although any retrospective study can only identify associations and not prove causal relationships, this study provides us with evidence that may influence how we manage patients. Specifically, the association of driving pressures at the end of surgery confirms what we have learned from the nontransplant anesthesiology literature: intraoperative ventilator management matters. Almost 10 y ago, Futier et al2 demonstrated the benefit of intraoperative lung-protective ventilation including the use of PEEP to prevent PPC after abdominal surgery with the landmark randomized, controlled Intraoperative Protective Ventilation trial. The benefit of using PEEP shown in the Intraoperative Protective Ventilation trial could not be replicated in the present study. This may reflect more recent evidence that suggests that high driving pressure (and tidal volumes) and not just low PEEP are actually harmful,3 and PEEP should be individualized to the patient’s static compliance. The ongoing Prime-Air study (ClinicalTrials.gov Identifier: NCT04108130) is a large, multicenter, randomized, controlled trial of an anesthetic-center bundle of interventions that includes individualized PEEP. This study will likely provide us with a better understanding if and how individualized PEEP may be beneficial. Other factors identified by this study associated with PPCs such as low albumin levels at the end of surgery and intraoperative hypotension require more complex physiologic explanations and are not as easily modifiable. PPCs are usually defined as any serious respiratory complications after surgery independent of their etiology.4 Cardiogenic pulmonary edema, pneumonias, and pleural effusions are all considered PPCs, although they represent very different pathologies. PPC is a syndrome with often vague and subjective definitions. For example, the severity of atelectasis or pleural effusion is difficult to quantify and what some may consider normal postoperative changes may be considered PPC by others. The elegant solution to this problem by the present study was to assess for PPCs with radiograph and chart review by 2 pulmonologists. Although this method allows for the application of some common sense in the diagnosis of PPC, it is harder to quantify severity. For example, is severe atelectasis equally harmful than pneumonia? Unlike other organ injuries such as acute kidney injury or liver failure, there are no proven sensitive and specific biomarkers that allow us to identify PPCs and assess its severity. This should not discourage us as it is a great opportunity for future research that may dramatically transform clinical studies of PPCs and possible interventions. The present study is further encouraging as it demonstrates that interventions in the operating room affect complications and the anesthesiologist as an integral member of transplant team can contribute to better outcomes for our patients.