Effect on post-operative pulmonary complications frequency of high flow nasal oxygen versus standard oxygen therapy in patients undergoing esophagectomy for cancer: study protocol for a randomized controlled trial-OSSIGENA study

Abstract

Background: Postoperative pulmonary complications (PPCs) remain a challenge after esophagectomy. Despite improvement in surgical and anesthesiological management, PPCs are reported in as many as 40% of patients. The main aim of this study is to investigate whether early application of high-flow nasal cannula (HFNC) after extubation will provide benefit in terms of reduced PPC frequency compared to standard oxygen therapy.

Methods: Patients aged 18-85 years undergoing esophagectomy for cancer treatment with radical intent, excluding those with American Society of Anesthesiologists (ASA) score >3 and severe systemic comorbidity (cardiac, pulmonary, renal or hepatic disease) will be randomized at the end of surgery to receive HFNC or standard oxygen therapy (Venturi mask or nasal goggles) after early extubation (within 12 hours after the end of surgery) for 48 hours. The main postoperative goals are to obtain SpO₂ ≥94% and adequate pain control. Oxygen therapy after 48 hours will be stopped unless the physician deems it necessary. In case of respiratory clinical worsening, patients will be supported with the most appropriate tool (noninvasive ventilation or invasive mechanical ventilation). Pulmonary [pneumonia, pleural effusion, pneumothorax, atelectasis, acute respiratory distress syndrome (ARDS), tracheo-bronchial injury, air leak, reintubation, and/or respiratory failure] complications will be recorded as main outcome. Secondary outcomes, including cardiovascular, surgical, renal and infective complications will also be recorded. The primary analysis will be carried out on 320 patients (160 per group) and performed on an intention-to-treat (ITT) basis, including all participants randomized into the treatment groups, regardless of protocol adherence. The primary outcome, the PPC rate, will be compared between the two treatment groups using a chi-square test for categorical data, or Fisher's exact test will be used if the assumptions for the chi-square test are not met.

Discussion: Recent evidence demonstrated that early application of HFNC improved the respiratory rate oxygenation index (ROX index) after esophagectomy but did not reduce PPCs. This randomized controlled multicenter trial aims to assess the potential effect of the application of HFNC versus standard oxygen over PPCs in patients undergoing esophagectomy.

Trial registration: This study is registered at clinicaltrial.gov NCT05718284, dated 30 January 2023.

Keywords: Esophagectomy; high-flow nasal cannula (HFNC); outcome; perioperative medicine; postoperative pulmonary complications (PPCs).

Figure 1

Study timeline. After extubation that will be performed within 12 hours after the end of surgery, patients will be randomized (T₀) to receive HFNC or COT for the following 48 hours. The primary oxygenation target will be to maintain SpO₂ ≥94% with the lowest FiO₂ possible. After this period (T₄₈), treatment will be stopped unless the physician deems it necessary. In case of clinical signs of respiratory worsening (ARF) during the period T₀–T₄₈, irrespective of the treatment assigned, patients will be treated with noninvasive or invasive respiratory support per the physician’s decision. Similarly, patients randomized to COT will be allowed to receive HFNC if increased NIRS is necessary. The main PPCs recorded within the first 30 days after surgery will be pneumonia, pleural effusion, pneumothorax, atelectasis, ARDS, tracheo-bronchial injury, air leak, reintubation and respiratory failure. After the initiation of oxygen treatment, for 72 hours, all parameters shown in the table in the lower right part of the figure will also be collected. Figure made with biorender.com. HFNC, high-flow nasal cannula; COT, conventional oxygen therapy; ARF, acute respiratory failure; NIV, noninvasive ventilation; ETI, endotracheal intubation; NRS, numerical rating scale for pain; HR, heart rate; NIBP, noninvasive blood pressure; RR, respiratory rate; VAS_OXY, visual analogue scale for the tolerance of the oxygen treatment delivered; PPC, postoperative pulmonary complication; NIRS, noninvasive respiratory support; VAS_DISP, visual analogue numeric scale for dyspnea.