The feasibility of extubation in the operating room after bilateral lung transplantation in adult emphysema patients: an observational retrospective study

The feasibility of extubation in the operating room after bilateral lung transplantation in adult... Abstract OBJECTIVES We introduced an extubation strategy for emphysema patients after bilateral lung transplantation. Patients who met the extubation criteria were extubated in the operating room (OR) followed by non-invasive ventilation, and the other patients were extubated in the intensive care unit (ICU). The primary objective was to determine the extubation rate. The secondary outcomes were to determine the factors allowing for extubation in the OR and the postoperative course. METHODS This study is a single-centre retrospective database analysis of 96 patients. Anaesthesia was performed using automated titration of total intravenous anaesthesia combined with thoracic epidural analgesia. Extubation criteria included arterial partial pressure oxygen (PaO2)/fraction of inspired oxygen (FiO2) ratio, chest radiograph, oedema and haemodynamic stability. Data were compared using non-parametric tests and expressed as median (interquartile ranges) or number (%). RESULTS Fifty-three (55%) patients were extubated in the OR (the OR group) with 1 requiring reintubation and 43 (45%) patients were extubated in the ICU (the ICU group). Preoperative pulmonary hypertension, the requirement for intraoperative extracorporeal membrane oxygenation (ECMO), bleeding and ex vivo lung reconditioning donors were lower in the OR group. At the end of the procedure, the PaO2/FiO2 ratio was better [352 (289–437) vs 206 (144–357), P = 0.004), and the need for postoperative ECMO, mechanical ventilation duration, length of stay in the ICU [5 (4–7) vs 12 (8–20) days, P < 0.0001], Grade 3 primary graft dysfunction at 72 h [1 (2%) vs 10 (24%), P = 0.002] and 1-year mortality [5 (9%) vs 11 (26%) patients, P = 0.014] were lower in the OR group than in the ICU group. CONCLUSIONS Half of patients were extubated in the OR, and this strategy does not require additional ICU resources. Bilateral lung transplantation , Emphysema , Extubation INTRODUCTION In the past decade, both the number of lung transplantations and the survival rate thereafter have increased dramatically. The most common primary indication for lung transplantation worldwide is emphysema [1]. Lung transplantation is a complex procedure, and invasive mechanical ventilation is the usual practice in the postoperative period [2]. Specifically, after lung transplantation, prolonged mechanical ventilation may carry associated risks of bronchial anastomosis damage [3]. Invasive mechanical ventilation in immunocompromised patients and endotracheal intubation are predisposing factors for developing nosocomial infections [4]. Moreover, invasive mechanical ventilation requires the use of sedative agents that may inhibit gastrointestinal motility [5]. For emphysema patients undergoing lung transplantation, extubation in the operating room (OR) is considered feasible. Previous reports have described extubation in the OR especially after single-lung transplantation for emphysema patients [6–8], but extubation after bilateral lung transplantation (BLT) has rarely been reported [9]. Early extubation can reduce the length of stay in the intensive care unit (ICU) and improve ICU resource utilization [10]. Since 2006, we have developed OR extubation guidelines at our institution for emphysema patients undergoing BLT. Patients with correct graft function at the end of BLT were extubated in the OR followed by non-invasive ventilation (NIV) [3, 7]. The primary objective of this retrospective analysis of the database was to evaluate the extubation rate in the OR using this strategy. The secondary outcomes were the determination of patient or intraoperative factors allowing for extubation in the OR and the evaluation of the postoperative course. We mainly compared the survival rate and the ICU resource utilization between patients extubated in the OR and patients extubated in the ICU. PATIENTS METHODS This study is a retrospective analysis of the prospectively maintained institutional Anaesthesia Lung Transplant Database. The database has received approval from the Institutional Review Board of the French Learned Society of Pneumology (Société de Pneumologie de Langue Française, 24 February 2012). Patient consent was waived. This cohort study was performed on emphysema patients undergoing BLT between May 2007 and September 2016 at a single centre (Foch Hospital, Suresnes, France). This centre maintains strict compliance with the ethics statement of the International Society for Heart and Lung Transplantation. Patients with single-lung transplantation, retransplantation, preoperative extracorporeal membrane oxygenation (ECMO) or multiorgan transplantation were excluded. BLT was performed using grafts from brain-dead donors with or without ex vivo lung reconditioning [11]. Donor characteristics were evaluated using the lung donor score [12]. Sequential BLT was performed using bilateral anterolateral thoracotomy. ECMO was placed during the procedure if required. Data were extracted from the medical records, including patient, donor and intraoperative and ICU characteristics. Before lung transplantation, we explained to patients who did not use NIV, how to use it and that the NIV will be used systematically after extubation. Procedure In the operating room The local anaesthesia protocol included a hot-air warming blanket and a thoracic epidural catheter (if there were no contraindications, a mixture of levobupivacaine and sufentanil was infused throughout the procedure). A right radial artery catheter, an oximetric pulmonary arterial catheter (Swan–Ganz continuous cardiac output or mixed venous oxygen saturation catheter; Edward Life Sciences Corp., Irvine, CA, USA), transoesophageal echocardiography (Vivid 7, GE healthcare, Fairfield, CT, USA) and a central venous catheter were inserted. To facilitate the drug administration during the procedure, we have developed a prototype allowing the automated titration of propofol and remifentanil using the bispectral index (Medtronic, Dublin, Ireland) to target a bispectral value between 40 and 60 during induction and maintenance of general anaesthesia [9, 13]. A low concentration of norepinephrine was infused systematically. An atracurium bolus was administered to facilitate tracheal intubation by a left double-lumen tube. The tube was controlled using a fibreoptic bronchoscopy. A tidal volume of 5–6 ml⋅kg−1 or 3–4 ml⋅kg−1 was used during double-lung or single-lung ventilation, respectively, associated with a positive end-expiratory pressure of 5 cm H2O. Tidal volumes were adjusted according to arterial blood gas analysis, and inhaled nitric oxide was systematically administered. At the end of the procedure, the endobronchial double-lumen tube was changed to a single-lumen tube. A fibreoptic bronchoscopy was performed for bronchial toilette to check for bronchial anastomosis or oedema, and recruitment manoeuvres were also performed. The possibility of extubation in the OR was evaluated if the patient met the following criteria, including a fully awake and alert state after the stop of propofol and remifentanil infusion and antagonism of neuromuscular block, body temperature ≥36°C, controlled blood loss (<100 ml⋅h−1) with an acceptable trend of haemodynamic stability, the absence of major pulmonary oedema evaluated using fibreoptic bronchoscopy, trend of blood gas analysis with arterial partial pressure oxygen (PaO2)/fraction of inspired oxygen (FiO2) ratio >200, lactataemia <3 mmol⋅l−1 and the absence of radiographic infiltrates on chest radiograph performed systematically before the extubation attempt in the OR. Extubation was performed in the OR in a sitting position followed by immediate NIV via a face mask using the Respironics® ventilator (Philips Healthcare, Netherlands). NIV parameters, such as FiO2, positive end-expiratory pressure and pressure support, were adapted to obtain an acceptable tidal volume, end-tidal CO2 and arterial saturation. We considered extubation to be a success if the patient under NIV was well orientated, pain free, without clinical signs of acute respiratory distress with acceptable blood gas analysis (PaO2/FiO2 ratio >150 and arterial pressure carbone dioxide (PaCO2) <50 mmHg or one similar to preoperative PaCO2). Patients were transferred to the ICU with NIV. In patients without a thoracic epidural catheter, pain control was performed using a multimodal approach with paracetamol, nefopam, ketamine and intravenous morphine titration followed by patient-controlled analgesia of intravenous morphine. Paravertebral catheters were not used in this series. In the intensive care unit Patients extubated in the OR (the OR group) were placed on NIV in the ICU. NIV parameters were adjusted according to blood gas analysis, arterial saturation and clinical tolerance. Patients in the ICU group were extubated at the discretion of the attending intensive care physician. Primary graft dysfunction (PGD) was evaluated during the initial 72 h postoperatively. Grade 3 PGD at 72 h was defined as a PaO2/FiO2 ratio <200, and bilateral infiltrates on chest radiograph were recorded 72 h postoperatively. Grade 3 PGD was also defined by the need for postoperative ECMO or the use of inhaled nitric oxide for >48 h during mechanical ventilation. Patients having hyperacute rejection, venous anastomotic obstruction, cardiogenic pulmonary oedema or pneumonia were excluded from Grade 3 PGD [14]. Within 24 h, a fibreoptic bronchoscopy with video recording was performed systematically on patients. The primary outcome was the incidence of patients extubated in the OR. Failure in the OR group was noted when the patient was reintubated in the OR or in the ICU within 48 h postoperatively. Patients extubated in the OR were allocated to the OR group, and patients extubated in the ICU were allocated to the ICU group. For the secondary outcomes, we evaluated the patient characteristics (demography, history and treatments), the donor characteristics, the intraoperative events (fluid loading, ECMO requirement and bleeding) and the postoperative course (the mechanical ventilation duration, the need for tracheostomy, the length of stay in the ICU and the Grade 3 PGD at 72 h). In particular, we analysed the survival rate to evaluate the safety of our strategy. In this observational study, the analysis of the data was performed without the use of risk-adjustment methods to decrease the bias. Indeed, the sample size was too small. Statistical analysis The OR and ICU groups were compared using non-parametric tests. The Boschloo’s test was used for all categorical variables except 1-month survival and 1-year survival. The Boschloo’s test is an unconditional test, it has the advantage of preserving significance level and is more powerful than the Fisher’s exact test for moderate to small samples. The Mann–Whitney U-test was used for all continuous variables. Categorical variables are presented as number (%) or number and frequencies with 95% confidence interval (CI) calculated using the Wilson procedure with a correction for continuity. Differences in time to 1-year survival were reported using the Kaplan–Meier curve, and statistical significance was calculated using the log-rank test. Continuous variables are presented as medians (25th–75th percentiles). All comparisons were performed without correction for multiple testing. A bilateral P-value <0.05 was considered statistically significant. Statistical analyses were performed using SPSS version 11.0 (SPSS Science Inc., Chicago, IL, USA) and R Core Team version 3.3.2 (R Foundation for Statistical Computing, Vienna, Austria) with the package Exact 2x2 version 1.5.2. RESULTS Between May 2007 and September 2016, 96 patients had sequential BLT using bilateral anterolateral thoracotomy (Fig. 1), and 53 patients (55%, CI95 45–65) were extubated in the OR and underwent NIV. One patient was reintubated: the patient had acute agitation and pain despite the use of thoracic epidural analgesia related to opioid-withdrawal syndrome. This patient was sedated, reintubated, mechanically ventilated within 12 h postoperatively and analysed in the OR group. Three patients among this group required tracheal intubation between the 4th and 6th postoperative day related to acute graft rejection, pneumonia or septic shock. The tracheal intubation was followed by a tracheotomy. Figure 1: View largeDownload slide Flowchart. ECMO: extracorporeal membrane oxygenation; ICU group: extubation in the ICU; ICU: intensive care unit; NIV: non-invasive ventilation; OR group: extubation in the OR; OR: operating room. Figure 1: View largeDownload slide Flowchart. ECMO: extracorporeal membrane oxygenation; ICU group: extubation in the ICU; ICU: intensive care unit; NIV: non-invasive ventilation; OR group: extubation in the OR; OR: operating room. Forty-three patients (45%, CI95 35–55) remained intubated at the end of the procedure (the ICU group) and were transferred to the ICU under mechanical ventilation (Fig. 1). However, 7 patients were extubated within 24 h postoperatively, and the reasons for non-extubation in the OR were related to the intraoperative requirement for ECMO (n = 3), the absence of thoracic epidural analgesia (n = 2), hypothermia (n = 1) and other (n = 1); no patients were reintubated within 48 h. Hence, 60 patients (62%, CI95 51–72) were extubated within 24 h postoperatively. Patient and donor characteristics were similar except for the number of ex vivo lung reconditioning and preoperative pulmonary hypertension (Table 1). Table 1: Patient and donor characteristics OR group (n = 53) ICU group (n = 43) P-value Patient characteristics  Age (years) 56 (49–59) 52 (45–57) 0.17  Male gender 30 (57) 22 (51) 0.68  Height (cm) 169 (163–176) 165 (160–172) 0.25  Weight (kg) 61 (52–75) 59 (51–70) 0.93  BMI (kg⋅m−2) 22 (19–25) 22 (19–26) 0.93  Preoperative pulmonary artery hypertension 16 (30) 22 (51) 0.04  Preoperative plasmapheresis 14 (26) 8 (19) 0.40  History of thoracic surgery 7 (13) 5 (12) 0.92  Diabetes 2 (4) 2 (5) 1  Preoperative tracheotomy 1(2) 2 (5) 0.69  Waiting list duration (days) 33 (12–71) 40 (13–87) 0.60 Donor characteristics  Age (years) 49 (35–61) 50 (38–59) 0.40  Smoking history (pack-years) 0 (0–5) 5 (0–18) 0.14  Secretions (points) 0 (0–2) 2 (0–3) 0.18  Chest X-ray (points) 2 (0–3) 1 (0–2) 0.38  PaO2/FiO2 ratio 400 (330–453) 348 (260–432) 0.06  Oto score 6 (4–7) 6 (4–8) 0.15  Ex vivo lung reconditioning 3 (6) 10 (23) 0.017  First graft ischaemic duration (min) 256 (216–301) 245 (217–349) 0.96  Second graft ischaemic duration (min) 363 (327–425) 383 (327–480) 0.26 OR group (n = 53) ICU group (n = 43) P-value Patient characteristics  Age (years) 56 (49–59) 52 (45–57) 0.17  Male gender 30 (57) 22 (51) 0.68  Height (cm) 169 (163–176) 165 (160–172) 0.25  Weight (kg) 61 (52–75) 59 (51–70) 0.93  BMI (kg⋅m−2) 22 (19–25) 22 (19–26) 0.93  Preoperative pulmonary artery hypertension 16 (30) 22 (51) 0.04  Preoperative plasmapheresis 14 (26) 8 (19) 0.40  History of thoracic surgery 7 (13) 5 (12) 0.92  Diabetes 2 (4) 2 (5) 1  Preoperative tracheotomy 1(2) 2 (5) 0.69  Waiting list duration (days) 33 (12–71) 40 (13–87) 0.60 Donor characteristics  Age (years) 49 (35–61) 50 (38–59) 0.40  Smoking history (pack-years) 0 (0–5) 5 (0–18) 0.14  Secretions (points) 0 (0–2) 2 (0–3) 0.18  Chest X-ray (points) 2 (0–3) 1 (0–2) 0.38  PaO2/FiO2 ratio 400 (330–453) 348 (260–432) 0.06  Oto score 6 (4–7) 6 (4–8) 0.15  Ex vivo lung reconditioning 3 (6) 10 (23) 0.017  First graft ischaemic duration (min) 256 (216–301) 245 (217–349) 0.96  Second graft ischaemic duration (min) 363 (327–425) 383 (327–480) 0.26 The results are expressed as median (25th–75th percentiles) or number (%). Secretion: none = 0, minor = 1, moderate = 2, major = 3; Chest X-ray: clear = 0, minor change = 1, opacity ≤1 lobe = 2, opacity >1 lobe = 3. All comparisons were performed without correction for multiple testing. BMI: body mass index; FiO2: fraction of inspired oxygen; ICU group: extubation in the intensive care unit; OR group: extubation in the operating room; PaO2: arterial partial pressure oxygen; pulmonary hypertension: pulmonary mean pressure >25 mmHg. Table 1: Patient and donor characteristics OR group (n = 53) ICU group (n = 43) P-value Patient characteristics  Age (years) 56 (49–59) 52 (45–57) 0.17  Male gender 30 (57) 22 (51) 0.68  Height (cm) 169 (163–176) 165 (160–172) 0.25  Weight (kg) 61 (52–75) 59 (51–70) 0.93  BMI (kg⋅m−2) 22 (19–25) 22 (19–26) 0.93  Preoperative pulmonary artery hypertension 16 (30) 22 (51) 0.04  Preoperative plasmapheresis 14 (26) 8 (19) 0.40  History of thoracic surgery 7 (13) 5 (12) 0.92  Diabetes 2 (4) 2 (5) 1  Preoperative tracheotomy 1(2) 2 (5) 0.69  Waiting list duration (days) 33 (12–71) 40 (13–87) 0.60 Donor characteristics  Age (years) 49 (35–61) 50 (38–59) 0.40  Smoking history (pack-years) 0 (0–5) 5 (0–18) 0.14  Secretions (points) 0 (0–2) 2 (0–3) 0.18  Chest X-ray (points) 2 (0–3) 1 (0–2) 0.38  PaO2/FiO2 ratio 400 (330–453) 348 (260–432) 0.06  Oto score 6 (4–7) 6 (4–8) 0.15  Ex vivo lung reconditioning 3 (6) 10 (23) 0.017  First graft ischaemic duration (min) 256 (216–301) 245 (217–349) 0.96  Second graft ischaemic duration (min) 363 (327–425) 383 (327–480) 0.26 OR group (n = 53) ICU group (n = 43) P-value Patient characteristics  Age (years) 56 (49–59) 52 (45–57) 0.17  Male gender 30 (57) 22 (51) 0.68  Height (cm) 169 (163–176) 165 (160–172) 0.25  Weight (kg) 61 (52–75) 59 (51–70) 0.93  BMI (kg⋅m−2) 22 (19–25) 22 (19–26) 0.93  Preoperative pulmonary artery hypertension 16 (30) 22 (51) 0.04  Preoperative plasmapheresis 14 (26) 8 (19) 0.40  History of thoracic surgery 7 (13) 5 (12) 0.92  Diabetes 2 (4) 2 (5) 1  Preoperative tracheotomy 1(2) 2 (5) 0.69  Waiting list duration (days) 33 (12–71) 40 (13–87) 0.60 Donor characteristics  Age (years) 49 (35–61) 50 (38–59) 0.40  Smoking history (pack-years) 0 (0–5) 5 (0–18) 0.14  Secretions (points) 0 (0–2) 2 (0–3) 0.18  Chest X-ray (points) 2 (0–3) 1 (0–2) 0.38  PaO2/FiO2 ratio 400 (330–453) 348 (260–432) 0.06  Oto score 6 (4–7) 6 (4–8) 0.15  Ex vivo lung reconditioning 3 (6) 10 (23) 0.017  First graft ischaemic duration (min) 256 (216–301) 245 (217–349) 0.96  Second graft ischaemic duration (min) 363 (327–425) 383 (327–480) 0.26 The results are expressed as median (25th–75th percentiles) or number (%). Secretion: none = 0, minor = 1, moderate = 2, major = 3; Chest X-ray: clear = 0, minor change = 1, opacity ≤1 lobe = 2, opacity >1 lobe = 3. All comparisons were performed without correction for multiple testing. BMI: body mass index; FiO2: fraction of inspired oxygen; ICU group: extubation in the intensive care unit; OR group: extubation in the operating room; PaO2: arterial partial pressure oxygen; pulmonary hypertension: pulmonary mean pressure >25 mmHg. Thoracic epidural catheters were placed in 86% (CI95 77–92) of patients (Table 2). Three patients in the OR group had a contraindication for epidural insertion (2 post-plasmapheresis coagulopathies and 1 preoperative anticoagulant therapy), and 1 patient had failure of epidural catheter insertion. For the ICU group, we had 1 failure of catheter insertion and 8 contraindications for epidural insertion (2 post-plasmapheresis coagulopathies and 6 preoperative anticoagulant therapies). For the 9 patients in the ICU group without thoracic epidural analgesia, the PaO2/FiO2 ratio at the end of the procedure was higher than 300 for 4 patients, and 2 patients were extubated within 24 h in the ICU. Table 2: Intraoperative data OR group (n = 53) ICU group (n = 43) P-value Thoracic epidural catheter 49 (92) 34 (79) 0.07 Major anaesthetic induction complications 3 (6) 6 (14) 0.22 Cardiopulmonary bypass 2 (4) 4 (9) 0.40 Intraoperative ECMO 3 (6) 19 (44) <0.0001 Intraoperative ECMO duration 253 (191–284) 229 (175–320) 1 Procedure duration (min) 560 (480–639) 571 (460–596) 0.83 Total bleeding (ml) 800 (500–1500) 1150 (700–2000) 0.01 Red blood cells (unit) 4 (2–5) 4 (2–6) 0.14 Fresh frozen plasma (unit) 3 (2–5) 4 (2–6) 0.07 Crystalloids (ml⋅kg−1⋅h−1) 2 (2–3) 2 (1–3) 0.89 Colloids (ml⋅kg−1⋅h−1) 2 (2–3) 3 (2–4) 0.10 Patients receiving platelets 5 (10) 9 (21) 0.14 Lactataemia (mmol⋅l−1) 1.6 (1.3–2.6) 2.6 (1.9–5.0) <0.0001 PaO2/FiO2 ratio 358 (290–437) 206 (144–357) <0.0001 OR group (n = 53) ICU group (n = 43) P-value Thoracic epidural catheter 49 (92) 34 (79) 0.07 Major anaesthetic induction complications 3 (6) 6 (14) 0.22 Cardiopulmonary bypass 2 (4) 4 (9) 0.40 Intraoperative ECMO 3 (6) 19 (44) <0.0001 Intraoperative ECMO duration 253 (191–284) 229 (175–320) 1 Procedure duration (min) 560 (480–639) 571 (460–596) 0.83 Total bleeding (ml) 800 (500–1500) 1150 (700–2000) 0.01 Red blood cells (unit) 4 (2–5) 4 (2–6) 0.14 Fresh frozen plasma (unit) 3 (2–5) 4 (2–6) 0.07 Crystalloids (ml⋅kg−1⋅h−1) 2 (2–3) 2 (1–3) 0.89 Colloids (ml⋅kg−1⋅h−1) 2 (2–3) 3 (2–4) 0.10 Patients receiving platelets 5 (10) 9 (21) 0.14 Lactataemia (mmol⋅l−1) 1.6 (1.3–2.6) 2.6 (1.9–5.0) <0.0001 PaO2/FiO2 ratio 358 (290–437) 206 (144–357) <0.0001 The results are expressed as median (25th–75th percentiles) or number (%). All comparisons were performed without correction for multiple testing. ECMO: extracorporeal membrane oxygenation; FiO2: fraction of inspired oxygen; ICU group: extubation in the intensive care unit; major anaesthetic induction complication: major hypotension (use of epinephrine), difficult tracheal intubation or pneumothorax; OR group: extubation in the operating room; PaO2: arterial partial pressure oxygen; procedure duration: entry of the patient into the OR until the transfer to the ICU. Table 2: Intraoperative data OR group (n = 53) ICU group (n = 43) P-value Thoracic epidural catheter 49 (92) 34 (79) 0.07 Major anaesthetic induction complications 3 (6) 6 (14) 0.22 Cardiopulmonary bypass 2 (4) 4 (9) 0.40 Intraoperative ECMO 3 (6) 19 (44) <0.0001 Intraoperative ECMO duration 253 (191–284) 229 (175–320) 1 Procedure duration (min) 560 (480–639) 571 (460–596) 0.83 Total bleeding (ml) 800 (500–1500) 1150 (700–2000) 0.01 Red blood cells (unit) 4 (2–5) 4 (2–6) 0.14 Fresh frozen plasma (unit) 3 (2–5) 4 (2–6) 0.07 Crystalloids (ml⋅kg−1⋅h−1) 2 (2–3) 2 (1–3) 0.89 Colloids (ml⋅kg−1⋅h−1) 2 (2–3) 3 (2–4) 0.10 Patients receiving platelets 5 (10) 9 (21) 0.14 Lactataemia (mmol⋅l−1) 1.6 (1.3–2.6) 2.6 (1.9–5.0) <0.0001 PaO2/FiO2 ratio 358 (290–437) 206 (144–357) <0.0001 OR group (n = 53) ICU group (n = 43) P-value Thoracic epidural catheter 49 (92) 34 (79) 0.07 Major anaesthetic induction complications 3 (6) 6 (14) 0.22 Cardiopulmonary bypass 2 (4) 4 (9) 0.40 Intraoperative ECMO 3 (6) 19 (44) <0.0001 Intraoperative ECMO duration 253 (191–284) 229 (175–320) 1 Procedure duration (min) 560 (480–639) 571 (460–596) 0.83 Total bleeding (ml) 800 (500–1500) 1150 (700–2000) 0.01 Red blood cells (unit) 4 (2–5) 4 (2–6) 0.14 Fresh frozen plasma (unit) 3 (2–5) 4 (2–6) 0.07 Crystalloids (ml⋅kg−1⋅h−1) 2 (2–3) 2 (1–3) 0.89 Colloids (ml⋅kg−1⋅h−1) 2 (2–3) 3 (2–4) 0.10 Patients receiving platelets 5 (10) 9 (21) 0.14 Lactataemia (mmol⋅l−1) 1.6 (1.3–2.6) 2.6 (1.9–5.0) <0.0001 PaO2/FiO2 ratio 358 (290–437) 206 (144–357) <0.0001 The results are expressed as median (25th–75th percentiles) or number (%). All comparisons were performed without correction for multiple testing. ECMO: extracorporeal membrane oxygenation; FiO2: fraction of inspired oxygen; ICU group: extubation in the intensive care unit; major anaesthetic induction complication: major hypotension (use of epinephrine), difficult tracheal intubation or pneumothorax; OR group: extubation in the operating room; PaO2: arterial partial pressure oxygen; procedure duration: entry of the patient into the OR until the transfer to the ICU. The blood loss or total bleeding was higher in the ICU group (Table 2). The requirement for intraoperative ECMO was lower in the OR group (Table 2). The use of intraoperative ECMO (n = 22) increased bleeding [1800 (1100–3750) vs 900 (500–1400) ml, P = 0.001], the units of red blood cells [4 (4–11) vs 3 (2–5), P = 0.007] and the units of fresh frozen plasma [6 (4–11) vs 3 (2–4), P = 0.001]. As expected at the end of the procedure, the PaO2/FiO2 ratio was higher, and the lactataemia was lower in the OR group (Table 2). The postoperative courses differed between groups. The duration of invasive mechanical ventilation, the length of stay in the ICU, the need for tracheotomy or postoperative ECMO were lower in the OR group (Table 3). Moreover, as expected, the rate of Grade 3 PGD at 72 h was lower in the OR group. One-year mortality data were obtained for all patients and were lower in the OR group (Table 3 and Fig. 2). In the overall population, 1-month survival rate was 92% (CI95 84–96), and 1-year survival was 83% (CI95 74–90). Table 3: Postoperative data OR group (n = 53) ICU group (n = 43) P-value Length of stay in the ICU (days) 5 (4–7) 12 (8–20) <0.0001 Reintubation in the OR or the ICU 1 (2) NA Postoperative ECMO 0 (0) 9 (21) <0.0001 Mechanical ventilation duration (days) 0 (0–1) 8 (3–14) <0.0001 Tracheotomy 3 (6) 16 (37) <0.0001 Grade 3 primary graft dysfunction at 72 h 1 (2) 10 (24) 0.001 1-Month survival 52 (98) 36 (84) 1-Year survival 48 (91) 32 (74) 0.014a OR group (n = 53) ICU group (n = 43) P-value Length of stay in the ICU (days) 5 (4–7) 12 (8–20) <0.0001 Reintubation in the OR or the ICU 1 (2) NA Postoperative ECMO 0 (0) 9 (21) <0.0001 Mechanical ventilation duration (days) 0 (0–1) 8 (3–14) <0.0001 Tracheotomy 3 (6) 16 (37) <0.0001 Grade 3 primary graft dysfunction at 72 h 1 (2) 10 (24) 0.001 1-Month survival 52 (98) 36 (84) 1-Year survival 48 (91) 32 (74) 0.014a The results are expressed as median (25th–75th percentiles) or number (%). All comparisons were performed without correction for multiple testing. a P-value was calculated using the log-rank test. ECMO: extracorporeal membrane oxygenation; Grade 3 primary graft dysfunction at 72 h: PaO2/FiO2 ratio <200 and bilateral infiltrates on chest X-ray at 72 h, the use of ECMO or inhaled pulmonary vasodilatator >48 h; ICU group: extubation in the intensive care unit; OR group: extubation in the operating room. Table 3: Postoperative data OR group (n = 53) ICU group (n = 43) P-value Length of stay in the ICU (days) 5 (4–7) 12 (8–20) <0.0001 Reintubation in the OR or the ICU 1 (2) NA Postoperative ECMO 0 (0) 9 (21) <0.0001 Mechanical ventilation duration (days) 0 (0–1) 8 (3–14) <0.0001 Tracheotomy 3 (6) 16 (37) <0.0001 Grade 3 primary graft dysfunction at 72 h 1 (2) 10 (24) 0.001 1-Month survival 52 (98) 36 (84) 1-Year survival 48 (91) 32 (74) 0.014a OR group (n = 53) ICU group (n = 43) P-value Length of stay in the ICU (days) 5 (4–7) 12 (8–20) <0.0001 Reintubation in the OR or the ICU 1 (2) NA Postoperative ECMO 0 (0) 9 (21) <0.0001 Mechanical ventilation duration (days) 0 (0–1) 8 (3–14) <0.0001 Tracheotomy 3 (6) 16 (37) <0.0001 Grade 3 primary graft dysfunction at 72 h 1 (2) 10 (24) 0.001 1-Month survival 52 (98) 36 (84) 1-Year survival 48 (91) 32 (74) 0.014a The results are expressed as median (25th–75th percentiles) or number (%). All comparisons were performed without correction for multiple testing. a P-value was calculated using the log-rank test. ECMO: extracorporeal membrane oxygenation; Grade 3 primary graft dysfunction at 72 h: PaO2/FiO2 ratio <200 and bilateral infiltrates on chest X-ray at 72 h, the use of ECMO or inhaled pulmonary vasodilatator >48 h; ICU group: extubation in the intensive care unit; OR group: extubation in the operating room. Figure 2: View largeDownload slide One-year overall survival using the Kaplan–Meier method. The solid blue line indicates survival of patients extubated in the OR group. The solid red line indicates survival of patients extubated in the ICU group after bilateral lung transplantation. Dotted lines indicate confidence limits (95%). ICU: intensive care unit; OR: operating room. Figure 2: View largeDownload slide One-year overall survival using the Kaplan–Meier method. The solid blue line indicates survival of patients extubated in the OR group. The solid red line indicates survival of patients extubated in the ICU group after bilateral lung transplantation. Dotted lines indicate confidence limits (95%). ICU: intensive care unit; OR: operating room. For the patients (n = 11) with Grade 3 PGD at 72 h, the intraoperative fluid administration of red blood cell [7 (4–10) vs 4 (4–11) units, P = 0.03], fresh frozen plasma [8 (4–11) vs 6 (4–8), P = 0.02] or colloid [3 (2–5) vs 2 (1–3) ml⋅kg−1⋅h−1, P = 0.005] was increased as compared to patients with PGD grade <3 (n = 84), whereas total bleeding [1500 (675–4250) vs 1000 (575–1525) ml, P = 0.16] and the rate of intraoperative ECMO [4 (36%) vs 18 (21%), P = 0.27] were similar in patients with Grade 3 and patients with Grade <3. In patients with Grade 3 PGD at 72 h, 1-year survival was 56% (CI95 26–83). For the patients (n = 13) receiving from an ex vivo lung reconditioning donor, as expected PaO2/FiO2 ratio of the donor was lower [250 (189–314) vs 400 (325–465), P < 0.0001], the Oto score was higher [9 (6–9) vs 6 (4–8), P = 0.008] and the first graft ischaemic durations were doubled [535 (465–666) vs 246 (211–288) min, P = 0.002] from an ex vivo lung reconditioning procedure as compared to conventional donors, respectively. At the end of the procedure, the PaO2/FiO2 ratio 224 (111–350) vs 324 (212–426) was lower for patients receiving from an ex vivo lung reconditioning donor as compared to patients receiving conventional donor lungs. However, the occurrence of Grade 3 PGD at 72 h [0 (0%) vs 11 (13%)] and the 1-month survival [13 (100%) vs 75 (90%)] or 1-year survival [13 (100%) vs 56 (77%)] were similar between ex vivo lung reconditioning and conventional donor lungs. No case of intraoperative recall was recorded. DISCUSSION In emphysema patients undergoing BLT, extubation in the OR followed by NIV was possible for half of the patients after combining thoracic epidural analgesia with total intravenous anaesthesia. Preoperative pulmonary hypertension, the grafts obtained after ex vivo lung conditioning, the requirement for intraoperative ECMO or major bleeding decreased the possibility of extubation in the OR. For patients extubated in the OR, the postoperative course or prognosis was not altered. Extubation in the OR after lung transplantation is considered as a goal for some teams [6–8], but the feasibility of extubation for emphysema patients after BLT has rarely been reported. In an observational study, we have reported extubation in the OR for 3 of 5 emphysema patients after BLT, and none of the patients were reintubated [9]. Other studies have reported only the feasibility of extubation after single-lung transplantation in emphysema patients. In a series of 6 patients, 2 were extubated in the OR [7]. In 91 patients, 53% were extubated in the OR, but 21% of these patients were reintubated [6]. In a series of 57 patients, 21 (37%) patients were extubated in the OR, and 2 (10%) patients were reintubated [8]. After BLT, the rate of extubation in the OR has been reported mainly in cystic fibrosis patients. Recently, a study of 89 cystic fibrosis patients undergoing BLT reported that 45 patients were extubated in the OR, and 4 were reintubated [15]. The success rate of early extubation was probably related to the systematic use of NIV [3]. Indeed, NIV is effective in improving gas exchange of either PaO2 or PaCO2 without sedation [16] after BLT [3]. Finally, the strategy for extubation in the OR was feasible without an increase in procedure duration (Table 2). The anaesthetic approach allowing for early extubation includes effective analgesia, normothermia, the use of short-acting anaesthetic drugs [5, 6, 17] and a skilled anaesthesiologist to maintain cardiorespiratory homeostasis continuously. In the absence of contraindication, thoracic epidural analgesia is the standard for postoperative pain control after bilateral thoracotomy: thoracic epidural analgesia decreases the duration of mechanical ventilation, the length of stay in the ICU and the rate of respiratory complication [18]. In this study, 4 patients without thoracic epidural analgesia were not extubated at the end of the procedure although they had met the criteria for extubation in the OR. Indeed, pain control after bilateral thoracotomy without epidural analgesia with a multimodal approach can induce sedation and respiratory depression. Epidural haematoma has never been described during lung transplantation, but a very low risk of haematoma exists [19]. The use of short-acting anaesthetic drugs needs continuous control and vigilance by the anaesthesiologist to avoid drug overdosing, thereby reducing side effects such as vasoplegia and vasopressor use [20]. The maintenance of anaesthesia was performed in all patients using an automated controller of total intravenous anaesthesia, allowing for the continuous titration of propofol and remifentanil guided by the electrocortical activity [13]. The protocol of our department was to use the controller systematically to reduce the workload [21] during this long and complicated procedure [9]. Extubation in the OR involves continuous interdisciplinary communication and cooperation among all members of the team. The need for ECMO was related to cardiopulmonary instability during the procedure and was associated with an increase in intraoperative bleeding (Table 2). Intraoperative instability as expected decreased the possibility of early extubation. For the anaesthesiologist, when the patient had an ECMO, the weaning from an assist device was prioritized over tracheal extubation. Intraoperative ECMO requirement and major bleeding have previously been reported to reduce the probability of early extubation in cystic fibrosis patients [15]. Ex vivo lung reconditioning [11] was used for rejected donor lungs with a low PaO2/FiO2 ratio and decreased extubation rate in the OR. While ischaemic graft duration is increased by the ex vivo procedure, there are no increase in the rate of Grade 3 PGD or one-year mortality as compared to conventional donors. This survival rate after the use of grafts provided by ex vivo lung reconditioning was similar to our experience [22]. As expected, postoperative ECMO requirement or the Grade 3 PGD [14] at 72 h were less frequent in the OR group. The criteria (PaO2/FiO2 ratio, chest radiograph or oedema) for extubation or for the evaluation of PGD are similar. These criteria at the end of the surgery in the OR were an early predictive marker of graft function, and the survival rate (Fig. 2) demonstrates that extubation in the OR seems to have no safety concerns. As also expected, extubation in the OR decreased mechanical ventilation duration, the length of stay in the ICU and the need for tracheotomy (Table 3). This association does not imply causality, but it was related to patient selection in the OR group. Finally, this strategy does not require additional ICU resources. Indeed, the need for critical care has dramatically increased due to the increase in candidates having ECMO before or after lung transplantation [23], and ICU resources are sometimes limited. The patients with Grade 3 PGD at 72 h (n = 11) received more packed red blood cells, fresh frozen plasma and colloid during the intraoperative period, while the rate of total intraoperative bleeding was similar. The increase in the intraoperative fluid administration has been reported as a factor associated with an increased rate of Grade 3 PGD [24]. Limitations This study is a retrospective analysis of a database from a single centre. It did not demonstrate that outcomes were different when the extubation was performed in the OR versus a few hours later in the ICU, when the patients had met the extubation criteria. Currently, the rate of emphysema patients extubated in the OR or within 24 h postoperatively after BLT has never been reported and remains unknown. The use of risk-adjustment methods (stratification, multivariate analysis, propensity score and so on) was not performed in this study. Indeed, the sample size was too small to perform a robust and accurate analysis. Over a 10-year period in a single institution, more than half of the adult emphysema patients could be extubated in the OR after BLT. This strategy involves a dynamic optimization of patient care, a rigorous selection of patients or grafts by skilled physicians and also close cooperation among all staff managing the candidates for lung transplantation. Extubation in the OR appears safe without the need for additional ICU resources in the postoperative period. ACKNOWLEDGEMENTS The authors thank Desmond McGlade, MBBS, FANZCA, Department of Anaesthesia, St. Vincent’s Hospital, Melbourne, Victoria, for his assistance on this article. Funding This work was supported by the Department of Anesthesiology, Hospital Foch, Suresnes, France, and Vaincre la Mucoviscidose, Paris France. Conflict of interest: Marc Fischler is the President of the Scientific Committee of MedSteer, which is a biomedical society promoting research and development of closed-loop tools. Ngai Liu is a cofounder of MedSteer, which is a biomedical society promoting research and development of closed-loop tools. All other authors declared no conflict of interest. REFERENCES 1 Yusen RD , Edwards LB , Dipchand AI , Goldfarb SB , Kucheryavaya AY , Levvey BJ et al. The Registry of the International Society for Heart and Lung Transplantation: thirty-third Adult Lung and Heart-Lung Transplant Report-2016; Focus Theme: primary Diagnostic Indications for Transplant . J Heart Lung Transplant 2016 ; 35 : 1170 – 84 . Google Scholar CrossRef Search ADS PubMed 2 Thakuria L , Davey R , Romano R , Carby MR , Kaul S , Griffiths MJ et al. Mechanical ventilation after lung transplantation . J Crit Care 2016 ; 31 : 110 – 18 . Google Scholar CrossRef Search ADS PubMed 3 Feltracco P , Serra E , Barbieri S , Milevoj M , Furnari M , Rizzi S et al. Noninvasive ventilation in postoperative care of lung transplant recipients. Transplant Proc 2009 ; 41 : 1339 – 44 . 4 Antonelli M , Conti G , Bufi M , Costa MG , Lappa A , Rocco M et al. 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The feasibility of extubation in the operating room after bilateral lung transplantation in adult emphysema patients: an observational retrospective study

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Oxford University Press
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© The Author(s) 2018. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.
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1010-7940
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10.1093/ejcts/ezy196
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Abstract

Abstract OBJECTIVES We introduced an extubation strategy for emphysema patients after bilateral lung transplantation. Patients who met the extubation criteria were extubated in the operating room (OR) followed by non-invasive ventilation, and the other patients were extubated in the intensive care unit (ICU). The primary objective was to determine the extubation rate. The secondary outcomes were to determine the factors allowing for extubation in the OR and the postoperative course. METHODS This study is a single-centre retrospective database analysis of 96 patients. Anaesthesia was performed using automated titration of total intravenous anaesthesia combined with thoracic epidural analgesia. Extubation criteria included arterial partial pressure oxygen (PaO2)/fraction of inspired oxygen (FiO2) ratio, chest radiograph, oedema and haemodynamic stability. Data were compared using non-parametric tests and expressed as median (interquartile ranges) or number (%). RESULTS Fifty-three (55%) patients were extubated in the OR (the OR group) with 1 requiring reintubation and 43 (45%) patients were extubated in the ICU (the ICU group). Preoperative pulmonary hypertension, the requirement for intraoperative extracorporeal membrane oxygenation (ECMO), bleeding and ex vivo lung reconditioning donors were lower in the OR group. At the end of the procedure, the PaO2/FiO2 ratio was better [352 (289–437) vs 206 (144–357), P = 0.004), and the need for postoperative ECMO, mechanical ventilation duration, length of stay in the ICU [5 (4–7) vs 12 (8–20) days, P < 0.0001], Grade 3 primary graft dysfunction at 72 h [1 (2%) vs 10 (24%), P = 0.002] and 1-year mortality [5 (9%) vs 11 (26%) patients, P = 0.014] were lower in the OR group than in the ICU group. CONCLUSIONS Half of patients were extubated in the OR, and this strategy does not require additional ICU resources. Bilateral lung transplantation , Emphysema , Extubation INTRODUCTION In the past decade, both the number of lung transplantations and the survival rate thereafter have increased dramatically. The most common primary indication for lung transplantation worldwide is emphysema [1]. Lung transplantation is a complex procedure, and invasive mechanical ventilation is the usual practice in the postoperative period [2]. Specifically, after lung transplantation, prolonged mechanical ventilation may carry associated risks of bronchial anastomosis damage [3]. Invasive mechanical ventilation in immunocompromised patients and endotracheal intubation are predisposing factors for developing nosocomial infections [4]. Moreover, invasive mechanical ventilation requires the use of sedative agents that may inhibit gastrointestinal motility [5]. For emphysema patients undergoing lung transplantation, extubation in the operating room (OR) is considered feasible. Previous reports have described extubation in the OR especially after single-lung transplantation for emphysema patients [6–8], but extubation after bilateral lung transplantation (BLT) has rarely been reported [9]. Early extubation can reduce the length of stay in the intensive care unit (ICU) and improve ICU resource utilization [10]. Since 2006, we have developed OR extubation guidelines at our institution for emphysema patients undergoing BLT. Patients with correct graft function at the end of BLT were extubated in the OR followed by non-invasive ventilation (NIV) [3, 7]. The primary objective of this retrospective analysis of the database was to evaluate the extubation rate in the OR using this strategy. The secondary outcomes were the determination of patient or intraoperative factors allowing for extubation in the OR and the evaluation of the postoperative course. We mainly compared the survival rate and the ICU resource utilization between patients extubated in the OR and patients extubated in the ICU. PATIENTS METHODS This study is a retrospective analysis of the prospectively maintained institutional Anaesthesia Lung Transplant Database. The database has received approval from the Institutional Review Board of the French Learned Society of Pneumology (Société de Pneumologie de Langue Française, 24 February 2012). Patient consent was waived. This cohort study was performed on emphysema patients undergoing BLT between May 2007 and September 2016 at a single centre (Foch Hospital, Suresnes, France). This centre maintains strict compliance with the ethics statement of the International Society for Heart and Lung Transplantation. Patients with single-lung transplantation, retransplantation, preoperative extracorporeal membrane oxygenation (ECMO) or multiorgan transplantation were excluded. BLT was performed using grafts from brain-dead donors with or without ex vivo lung reconditioning [11]. Donor characteristics were evaluated using the lung donor score [12]. Sequential BLT was performed using bilateral anterolateral thoracotomy. ECMO was placed during the procedure if required. Data were extracted from the medical records, including patient, donor and intraoperative and ICU characteristics. Before lung transplantation, we explained to patients who did not use NIV, how to use it and that the NIV will be used systematically after extubation. Procedure In the operating room The local anaesthesia protocol included a hot-air warming blanket and a thoracic epidural catheter (if there were no contraindications, a mixture of levobupivacaine and sufentanil was infused throughout the procedure). A right radial artery catheter, an oximetric pulmonary arterial catheter (Swan–Ganz continuous cardiac output or mixed venous oxygen saturation catheter; Edward Life Sciences Corp., Irvine, CA, USA), transoesophageal echocardiography (Vivid 7, GE healthcare, Fairfield, CT, USA) and a central venous catheter were inserted. To facilitate the drug administration during the procedure, we have developed a prototype allowing the automated titration of propofol and remifentanil using the bispectral index (Medtronic, Dublin, Ireland) to target a bispectral value between 40 and 60 during induction and maintenance of general anaesthesia [9, 13]. A low concentration of norepinephrine was infused systematically. An atracurium bolus was administered to facilitate tracheal intubation by a left double-lumen tube. The tube was controlled using a fibreoptic bronchoscopy. A tidal volume of 5–6 ml⋅kg−1 or 3–4 ml⋅kg−1 was used during double-lung or single-lung ventilation, respectively, associated with a positive end-expiratory pressure of 5 cm H2O. Tidal volumes were adjusted according to arterial blood gas analysis, and inhaled nitric oxide was systematically administered. At the end of the procedure, the endobronchial double-lumen tube was changed to a single-lumen tube. A fibreoptic bronchoscopy was performed for bronchial toilette to check for bronchial anastomosis or oedema, and recruitment manoeuvres were also performed. The possibility of extubation in the OR was evaluated if the patient met the following criteria, including a fully awake and alert state after the stop of propofol and remifentanil infusion and antagonism of neuromuscular block, body temperature ≥36°C, controlled blood loss (<100 ml⋅h−1) with an acceptable trend of haemodynamic stability, the absence of major pulmonary oedema evaluated using fibreoptic bronchoscopy, trend of blood gas analysis with arterial partial pressure oxygen (PaO2)/fraction of inspired oxygen (FiO2) ratio >200, lactataemia <3 mmol⋅l−1 and the absence of radiographic infiltrates on chest radiograph performed systematically before the extubation attempt in the OR. Extubation was performed in the OR in a sitting position followed by immediate NIV via a face mask using the Respironics® ventilator (Philips Healthcare, Netherlands). NIV parameters, such as FiO2, positive end-expiratory pressure and pressure support, were adapted to obtain an acceptable tidal volume, end-tidal CO2 and arterial saturation. We considered extubation to be a success if the patient under NIV was well orientated, pain free, without clinical signs of acute respiratory distress with acceptable blood gas analysis (PaO2/FiO2 ratio >150 and arterial pressure carbone dioxide (PaCO2) <50 mmHg or one similar to preoperative PaCO2). Patients were transferred to the ICU with NIV. In patients without a thoracic epidural catheter, pain control was performed using a multimodal approach with paracetamol, nefopam, ketamine and intravenous morphine titration followed by patient-controlled analgesia of intravenous morphine. Paravertebral catheters were not used in this series. In the intensive care unit Patients extubated in the OR (the OR group) were placed on NIV in the ICU. NIV parameters were adjusted according to blood gas analysis, arterial saturation and clinical tolerance. Patients in the ICU group were extubated at the discretion of the attending intensive care physician. Primary graft dysfunction (PGD) was evaluated during the initial 72 h postoperatively. Grade 3 PGD at 72 h was defined as a PaO2/FiO2 ratio <200, and bilateral infiltrates on chest radiograph were recorded 72 h postoperatively. Grade 3 PGD was also defined by the need for postoperative ECMO or the use of inhaled nitric oxide for >48 h during mechanical ventilation. Patients having hyperacute rejection, venous anastomotic obstruction, cardiogenic pulmonary oedema or pneumonia were excluded from Grade 3 PGD [14]. Within 24 h, a fibreoptic bronchoscopy with video recording was performed systematically on patients. The primary outcome was the incidence of patients extubated in the OR. Failure in the OR group was noted when the patient was reintubated in the OR or in the ICU within 48 h postoperatively. Patients extubated in the OR were allocated to the OR group, and patients extubated in the ICU were allocated to the ICU group. For the secondary outcomes, we evaluated the patient characteristics (demography, history and treatments), the donor characteristics, the intraoperative events (fluid loading, ECMO requirement and bleeding) and the postoperative course (the mechanical ventilation duration, the need for tracheostomy, the length of stay in the ICU and the Grade 3 PGD at 72 h). In particular, we analysed the survival rate to evaluate the safety of our strategy. In this observational study, the analysis of the data was performed without the use of risk-adjustment methods to decrease the bias. Indeed, the sample size was too small. Statistical analysis The OR and ICU groups were compared using non-parametric tests. The Boschloo’s test was used for all categorical variables except 1-month survival and 1-year survival. The Boschloo’s test is an unconditional test, it has the advantage of preserving significance level and is more powerful than the Fisher’s exact test for moderate to small samples. The Mann–Whitney U-test was used for all continuous variables. Categorical variables are presented as number (%) or number and frequencies with 95% confidence interval (CI) calculated using the Wilson procedure with a correction for continuity. Differences in time to 1-year survival were reported using the Kaplan–Meier curve, and statistical significance was calculated using the log-rank test. Continuous variables are presented as medians (25th–75th percentiles). All comparisons were performed without correction for multiple testing. A bilateral P-value <0.05 was considered statistically significant. Statistical analyses were performed using SPSS version 11.0 (SPSS Science Inc., Chicago, IL, USA) and R Core Team version 3.3.2 (R Foundation for Statistical Computing, Vienna, Austria) with the package Exact 2x2 version 1.5.2. RESULTS Between May 2007 and September 2016, 96 patients had sequential BLT using bilateral anterolateral thoracotomy (Fig. 1), and 53 patients (55%, CI95 45–65) were extubated in the OR and underwent NIV. One patient was reintubated: the patient had acute agitation and pain despite the use of thoracic epidural analgesia related to opioid-withdrawal syndrome. This patient was sedated, reintubated, mechanically ventilated within 12 h postoperatively and analysed in the OR group. Three patients among this group required tracheal intubation between the 4th and 6th postoperative day related to acute graft rejection, pneumonia or septic shock. The tracheal intubation was followed by a tracheotomy. Figure 1: View largeDownload slide Flowchart. ECMO: extracorporeal membrane oxygenation; ICU group: extubation in the ICU; ICU: intensive care unit; NIV: non-invasive ventilation; OR group: extubation in the OR; OR: operating room. Figure 1: View largeDownload slide Flowchart. ECMO: extracorporeal membrane oxygenation; ICU group: extubation in the ICU; ICU: intensive care unit; NIV: non-invasive ventilation; OR group: extubation in the OR; OR: operating room. Forty-three patients (45%, CI95 35–55) remained intubated at the end of the procedure (the ICU group) and were transferred to the ICU under mechanical ventilation (Fig. 1). However, 7 patients were extubated within 24 h postoperatively, and the reasons for non-extubation in the OR were related to the intraoperative requirement for ECMO (n = 3), the absence of thoracic epidural analgesia (n = 2), hypothermia (n = 1) and other (n = 1); no patients were reintubated within 48 h. Hence, 60 patients (62%, CI95 51–72) were extubated within 24 h postoperatively. Patient and donor characteristics were similar except for the number of ex vivo lung reconditioning and preoperative pulmonary hypertension (Table 1). Table 1: Patient and donor characteristics OR group (n = 53) ICU group (n = 43) P-value Patient characteristics  Age (years) 56 (49–59) 52 (45–57) 0.17  Male gender 30 (57) 22 (51) 0.68  Height (cm) 169 (163–176) 165 (160–172) 0.25  Weight (kg) 61 (52–75) 59 (51–70) 0.93  BMI (kg⋅m−2) 22 (19–25) 22 (19–26) 0.93  Preoperative pulmonary artery hypertension 16 (30) 22 (51) 0.04  Preoperative plasmapheresis 14 (26) 8 (19) 0.40  History of thoracic surgery 7 (13) 5 (12) 0.92  Diabetes 2 (4) 2 (5) 1  Preoperative tracheotomy 1(2) 2 (5) 0.69  Waiting list duration (days) 33 (12–71) 40 (13–87) 0.60 Donor characteristics  Age (years) 49 (35–61) 50 (38–59) 0.40  Smoking history (pack-years) 0 (0–5) 5 (0–18) 0.14  Secretions (points) 0 (0–2) 2 (0–3) 0.18  Chest X-ray (points) 2 (0–3) 1 (0–2) 0.38  PaO2/FiO2 ratio 400 (330–453) 348 (260–432) 0.06  Oto score 6 (4–7) 6 (4–8) 0.15  Ex vivo lung reconditioning 3 (6) 10 (23) 0.017  First graft ischaemic duration (min) 256 (216–301) 245 (217–349) 0.96  Second graft ischaemic duration (min) 363 (327–425) 383 (327–480) 0.26 OR group (n = 53) ICU group (n = 43) P-value Patient characteristics  Age (years) 56 (49–59) 52 (45–57) 0.17  Male gender 30 (57) 22 (51) 0.68  Height (cm) 169 (163–176) 165 (160–172) 0.25  Weight (kg) 61 (52–75) 59 (51–70) 0.93  BMI (kg⋅m−2) 22 (19–25) 22 (19–26) 0.93  Preoperative pulmonary artery hypertension 16 (30) 22 (51) 0.04  Preoperative plasmapheresis 14 (26) 8 (19) 0.40  History of thoracic surgery 7 (13) 5 (12) 0.92  Diabetes 2 (4) 2 (5) 1  Preoperative tracheotomy 1(2) 2 (5) 0.69  Waiting list duration (days) 33 (12–71) 40 (13–87) 0.60 Donor characteristics  Age (years) 49 (35–61) 50 (38–59) 0.40  Smoking history (pack-years) 0 (0–5) 5 (0–18) 0.14  Secretions (points) 0 (0–2) 2 (0–3) 0.18  Chest X-ray (points) 2 (0–3) 1 (0–2) 0.38  PaO2/FiO2 ratio 400 (330–453) 348 (260–432) 0.06  Oto score 6 (4–7) 6 (4–8) 0.15  Ex vivo lung reconditioning 3 (6) 10 (23) 0.017  First graft ischaemic duration (min) 256 (216–301) 245 (217–349) 0.96  Second graft ischaemic duration (min) 363 (327–425) 383 (327–480) 0.26 The results are expressed as median (25th–75th percentiles) or number (%). Secretion: none = 0, minor = 1, moderate = 2, major = 3; Chest X-ray: clear = 0, minor change = 1, opacity ≤1 lobe = 2, opacity >1 lobe = 3. All comparisons were performed without correction for multiple testing. BMI: body mass index; FiO2: fraction of inspired oxygen; ICU group: extubation in the intensive care unit; OR group: extubation in the operating room; PaO2: arterial partial pressure oxygen; pulmonary hypertension: pulmonary mean pressure >25 mmHg. Table 1: Patient and donor characteristics OR group (n = 53) ICU group (n = 43) P-value Patient characteristics  Age (years) 56 (49–59) 52 (45–57) 0.17  Male gender 30 (57) 22 (51) 0.68  Height (cm) 169 (163–176) 165 (160–172) 0.25  Weight (kg) 61 (52–75) 59 (51–70) 0.93  BMI (kg⋅m−2) 22 (19–25) 22 (19–26) 0.93  Preoperative pulmonary artery hypertension 16 (30) 22 (51) 0.04  Preoperative plasmapheresis 14 (26) 8 (19) 0.40  History of thoracic surgery 7 (13) 5 (12) 0.92  Diabetes 2 (4) 2 (5) 1  Preoperative tracheotomy 1(2) 2 (5) 0.69  Waiting list duration (days) 33 (12–71) 40 (13–87) 0.60 Donor characteristics  Age (years) 49 (35–61) 50 (38–59) 0.40  Smoking history (pack-years) 0 (0–5) 5 (0–18) 0.14  Secretions (points) 0 (0–2) 2 (0–3) 0.18  Chest X-ray (points) 2 (0–3) 1 (0–2) 0.38  PaO2/FiO2 ratio 400 (330–453) 348 (260–432) 0.06  Oto score 6 (4–7) 6 (4–8) 0.15  Ex vivo lung reconditioning 3 (6) 10 (23) 0.017  First graft ischaemic duration (min) 256 (216–301) 245 (217–349) 0.96  Second graft ischaemic duration (min) 363 (327–425) 383 (327–480) 0.26 OR group (n = 53) ICU group (n = 43) P-value Patient characteristics  Age (years) 56 (49–59) 52 (45–57) 0.17  Male gender 30 (57) 22 (51) 0.68  Height (cm) 169 (163–176) 165 (160–172) 0.25  Weight (kg) 61 (52–75) 59 (51–70) 0.93  BMI (kg⋅m−2) 22 (19–25) 22 (19–26) 0.93  Preoperative pulmonary artery hypertension 16 (30) 22 (51) 0.04  Preoperative plasmapheresis 14 (26) 8 (19) 0.40  History of thoracic surgery 7 (13) 5 (12) 0.92  Diabetes 2 (4) 2 (5) 1  Preoperative tracheotomy 1(2) 2 (5) 0.69  Waiting list duration (days) 33 (12–71) 40 (13–87) 0.60 Donor characteristics  Age (years) 49 (35–61) 50 (38–59) 0.40  Smoking history (pack-years) 0 (0–5) 5 (0–18) 0.14  Secretions (points) 0 (0–2) 2 (0–3) 0.18  Chest X-ray (points) 2 (0–3) 1 (0–2) 0.38  PaO2/FiO2 ratio 400 (330–453) 348 (260–432) 0.06  Oto score 6 (4–7) 6 (4–8) 0.15  Ex vivo lung reconditioning 3 (6) 10 (23) 0.017  First graft ischaemic duration (min) 256 (216–301) 245 (217–349) 0.96  Second graft ischaemic duration (min) 363 (327–425) 383 (327–480) 0.26 The results are expressed as median (25th–75th percentiles) or number (%). Secretion: none = 0, minor = 1, moderate = 2, major = 3; Chest X-ray: clear = 0, minor change = 1, opacity ≤1 lobe = 2, opacity >1 lobe = 3. All comparisons were performed without correction for multiple testing. BMI: body mass index; FiO2: fraction of inspired oxygen; ICU group: extubation in the intensive care unit; OR group: extubation in the operating room; PaO2: arterial partial pressure oxygen; pulmonary hypertension: pulmonary mean pressure >25 mmHg. Thoracic epidural catheters were placed in 86% (CI95 77–92) of patients (Table 2). Three patients in the OR group had a contraindication for epidural insertion (2 post-plasmapheresis coagulopathies and 1 preoperative anticoagulant therapy), and 1 patient had failure of epidural catheter insertion. For the ICU group, we had 1 failure of catheter insertion and 8 contraindications for epidural insertion (2 post-plasmapheresis coagulopathies and 6 preoperative anticoagulant therapies). For the 9 patients in the ICU group without thoracic epidural analgesia, the PaO2/FiO2 ratio at the end of the procedure was higher than 300 for 4 patients, and 2 patients were extubated within 24 h in the ICU. Table 2: Intraoperative data OR group (n = 53) ICU group (n = 43) P-value Thoracic epidural catheter 49 (92) 34 (79) 0.07 Major anaesthetic induction complications 3 (6) 6 (14) 0.22 Cardiopulmonary bypass 2 (4) 4 (9) 0.40 Intraoperative ECMO 3 (6) 19 (44) <0.0001 Intraoperative ECMO duration 253 (191–284) 229 (175–320) 1 Procedure duration (min) 560 (480–639) 571 (460–596) 0.83 Total bleeding (ml) 800 (500–1500) 1150 (700–2000) 0.01 Red blood cells (unit) 4 (2–5) 4 (2–6) 0.14 Fresh frozen plasma (unit) 3 (2–5) 4 (2–6) 0.07 Crystalloids (ml⋅kg−1⋅h−1) 2 (2–3) 2 (1–3) 0.89 Colloids (ml⋅kg−1⋅h−1) 2 (2–3) 3 (2–4) 0.10 Patients receiving platelets 5 (10) 9 (21) 0.14 Lactataemia (mmol⋅l−1) 1.6 (1.3–2.6) 2.6 (1.9–5.0) <0.0001 PaO2/FiO2 ratio 358 (290–437) 206 (144–357) <0.0001 OR group (n = 53) ICU group (n = 43) P-value Thoracic epidural catheter 49 (92) 34 (79) 0.07 Major anaesthetic induction complications 3 (6) 6 (14) 0.22 Cardiopulmonary bypass 2 (4) 4 (9) 0.40 Intraoperative ECMO 3 (6) 19 (44) <0.0001 Intraoperative ECMO duration 253 (191–284) 229 (175–320) 1 Procedure duration (min) 560 (480–639) 571 (460–596) 0.83 Total bleeding (ml) 800 (500–1500) 1150 (700–2000) 0.01 Red blood cells (unit) 4 (2–5) 4 (2–6) 0.14 Fresh frozen plasma (unit) 3 (2–5) 4 (2–6) 0.07 Crystalloids (ml⋅kg−1⋅h−1) 2 (2–3) 2 (1–3) 0.89 Colloids (ml⋅kg−1⋅h−1) 2 (2–3) 3 (2–4) 0.10 Patients receiving platelets 5 (10) 9 (21) 0.14 Lactataemia (mmol⋅l−1) 1.6 (1.3–2.6) 2.6 (1.9–5.0) <0.0001 PaO2/FiO2 ratio 358 (290–437) 206 (144–357) <0.0001 The results are expressed as median (25th–75th percentiles) or number (%). All comparisons were performed without correction for multiple testing. ECMO: extracorporeal membrane oxygenation; FiO2: fraction of inspired oxygen; ICU group: extubation in the intensive care unit; major anaesthetic induction complication: major hypotension (use of epinephrine), difficult tracheal intubation or pneumothorax; OR group: extubation in the operating room; PaO2: arterial partial pressure oxygen; procedure duration: entry of the patient into the OR until the transfer to the ICU. Table 2: Intraoperative data OR group (n = 53) ICU group (n = 43) P-value Thoracic epidural catheter 49 (92) 34 (79) 0.07 Major anaesthetic induction complications 3 (6) 6 (14) 0.22 Cardiopulmonary bypass 2 (4) 4 (9) 0.40 Intraoperative ECMO 3 (6) 19 (44) <0.0001 Intraoperative ECMO duration 253 (191–284) 229 (175–320) 1 Procedure duration (min) 560 (480–639) 571 (460–596) 0.83 Total bleeding (ml) 800 (500–1500) 1150 (700–2000) 0.01 Red blood cells (unit) 4 (2–5) 4 (2–6) 0.14 Fresh frozen plasma (unit) 3 (2–5) 4 (2–6) 0.07 Crystalloids (ml⋅kg−1⋅h−1) 2 (2–3) 2 (1–3) 0.89 Colloids (ml⋅kg−1⋅h−1) 2 (2–3) 3 (2–4) 0.10 Patients receiving platelets 5 (10) 9 (21) 0.14 Lactataemia (mmol⋅l−1) 1.6 (1.3–2.6) 2.6 (1.9–5.0) <0.0001 PaO2/FiO2 ratio 358 (290–437) 206 (144–357) <0.0001 OR group (n = 53) ICU group (n = 43) P-value Thoracic epidural catheter 49 (92) 34 (79) 0.07 Major anaesthetic induction complications 3 (6) 6 (14) 0.22 Cardiopulmonary bypass 2 (4) 4 (9) 0.40 Intraoperative ECMO 3 (6) 19 (44) <0.0001 Intraoperative ECMO duration 253 (191–284) 229 (175–320) 1 Procedure duration (min) 560 (480–639) 571 (460–596) 0.83 Total bleeding (ml) 800 (500–1500) 1150 (700–2000) 0.01 Red blood cells (unit) 4 (2–5) 4 (2–6) 0.14 Fresh frozen plasma (unit) 3 (2–5) 4 (2–6) 0.07 Crystalloids (ml⋅kg−1⋅h−1) 2 (2–3) 2 (1–3) 0.89 Colloids (ml⋅kg−1⋅h−1) 2 (2–3) 3 (2–4) 0.10 Patients receiving platelets 5 (10) 9 (21) 0.14 Lactataemia (mmol⋅l−1) 1.6 (1.3–2.6) 2.6 (1.9–5.0) <0.0001 PaO2/FiO2 ratio 358 (290–437) 206 (144–357) <0.0001 The results are expressed as median (25th–75th percentiles) or number (%). All comparisons were performed without correction for multiple testing. ECMO: extracorporeal membrane oxygenation; FiO2: fraction of inspired oxygen; ICU group: extubation in the intensive care unit; major anaesthetic induction complication: major hypotension (use of epinephrine), difficult tracheal intubation or pneumothorax; OR group: extubation in the operating room; PaO2: arterial partial pressure oxygen; procedure duration: entry of the patient into the OR until the transfer to the ICU. The blood loss or total bleeding was higher in the ICU group (Table 2). The requirement for intraoperative ECMO was lower in the OR group (Table 2). The use of intraoperative ECMO (n = 22) increased bleeding [1800 (1100–3750) vs 900 (500–1400) ml, P = 0.001], the units of red blood cells [4 (4–11) vs 3 (2–5), P = 0.007] and the units of fresh frozen plasma [6 (4–11) vs 3 (2–4), P = 0.001]. As expected at the end of the procedure, the PaO2/FiO2 ratio was higher, and the lactataemia was lower in the OR group (Table 2). The postoperative courses differed between groups. The duration of invasive mechanical ventilation, the length of stay in the ICU, the need for tracheotomy or postoperative ECMO were lower in the OR group (Table 3). Moreover, as expected, the rate of Grade 3 PGD at 72 h was lower in the OR group. One-year mortality data were obtained for all patients and were lower in the OR group (Table 3 and Fig. 2). In the overall population, 1-month survival rate was 92% (CI95 84–96), and 1-year survival was 83% (CI95 74–90). Table 3: Postoperative data OR group (n = 53) ICU group (n = 43) P-value Length of stay in the ICU (days) 5 (4–7) 12 (8–20) <0.0001 Reintubation in the OR or the ICU 1 (2) NA Postoperative ECMO 0 (0) 9 (21) <0.0001 Mechanical ventilation duration (days) 0 (0–1) 8 (3–14) <0.0001 Tracheotomy 3 (6) 16 (37) <0.0001 Grade 3 primary graft dysfunction at 72 h 1 (2) 10 (24) 0.001 1-Month survival 52 (98) 36 (84) 1-Year survival 48 (91) 32 (74) 0.014a OR group (n = 53) ICU group (n = 43) P-value Length of stay in the ICU (days) 5 (4–7) 12 (8–20) <0.0001 Reintubation in the OR or the ICU 1 (2) NA Postoperative ECMO 0 (0) 9 (21) <0.0001 Mechanical ventilation duration (days) 0 (0–1) 8 (3–14) <0.0001 Tracheotomy 3 (6) 16 (37) <0.0001 Grade 3 primary graft dysfunction at 72 h 1 (2) 10 (24) 0.001 1-Month survival 52 (98) 36 (84) 1-Year survival 48 (91) 32 (74) 0.014a The results are expressed as median (25th–75th percentiles) or number (%). All comparisons were performed without correction for multiple testing. a P-value was calculated using the log-rank test. ECMO: extracorporeal membrane oxygenation; Grade 3 primary graft dysfunction at 72 h: PaO2/FiO2 ratio <200 and bilateral infiltrates on chest X-ray at 72 h, the use of ECMO or inhaled pulmonary vasodilatator >48 h; ICU group: extubation in the intensive care unit; OR group: extubation in the operating room. Table 3: Postoperative data OR group (n = 53) ICU group (n = 43) P-value Length of stay in the ICU (days) 5 (4–7) 12 (8–20) <0.0001 Reintubation in the OR or the ICU 1 (2) NA Postoperative ECMO 0 (0) 9 (21) <0.0001 Mechanical ventilation duration (days) 0 (0–1) 8 (3–14) <0.0001 Tracheotomy 3 (6) 16 (37) <0.0001 Grade 3 primary graft dysfunction at 72 h 1 (2) 10 (24) 0.001 1-Month survival 52 (98) 36 (84) 1-Year survival 48 (91) 32 (74) 0.014a OR group (n = 53) ICU group (n = 43) P-value Length of stay in the ICU (days) 5 (4–7) 12 (8–20) <0.0001 Reintubation in the OR or the ICU 1 (2) NA Postoperative ECMO 0 (0) 9 (21) <0.0001 Mechanical ventilation duration (days) 0 (0–1) 8 (3–14) <0.0001 Tracheotomy 3 (6) 16 (37) <0.0001 Grade 3 primary graft dysfunction at 72 h 1 (2) 10 (24) 0.001 1-Month survival 52 (98) 36 (84) 1-Year survival 48 (91) 32 (74) 0.014a The results are expressed as median (25th–75th percentiles) or number (%). All comparisons were performed without correction for multiple testing. a P-value was calculated using the log-rank test. ECMO: extracorporeal membrane oxygenation; Grade 3 primary graft dysfunction at 72 h: PaO2/FiO2 ratio <200 and bilateral infiltrates on chest X-ray at 72 h, the use of ECMO or inhaled pulmonary vasodilatator >48 h; ICU group: extubation in the intensive care unit; OR group: extubation in the operating room. Figure 2: View largeDownload slide One-year overall survival using the Kaplan–Meier method. The solid blue line indicates survival of patients extubated in the OR group. The solid red line indicates survival of patients extubated in the ICU group after bilateral lung transplantation. Dotted lines indicate confidence limits (95%). ICU: intensive care unit; OR: operating room. Figure 2: View largeDownload slide One-year overall survival using the Kaplan–Meier method. The solid blue line indicates survival of patients extubated in the OR group. The solid red line indicates survival of patients extubated in the ICU group after bilateral lung transplantation. Dotted lines indicate confidence limits (95%). ICU: intensive care unit; OR: operating room. For the patients (n = 11) with Grade 3 PGD at 72 h, the intraoperative fluid administration of red blood cell [7 (4–10) vs 4 (4–11) units, P = 0.03], fresh frozen plasma [8 (4–11) vs 6 (4–8), P = 0.02] or colloid [3 (2–5) vs 2 (1–3) ml⋅kg−1⋅h−1, P = 0.005] was increased as compared to patients with PGD grade <3 (n = 84), whereas total bleeding [1500 (675–4250) vs 1000 (575–1525) ml, P = 0.16] and the rate of intraoperative ECMO [4 (36%) vs 18 (21%), P = 0.27] were similar in patients with Grade 3 and patients with Grade <3. In patients with Grade 3 PGD at 72 h, 1-year survival was 56% (CI95 26–83). For the patients (n = 13) receiving from an ex vivo lung reconditioning donor, as expected PaO2/FiO2 ratio of the donor was lower [250 (189–314) vs 400 (325–465), P < 0.0001], the Oto score was higher [9 (6–9) vs 6 (4–8), P = 0.008] and the first graft ischaemic durations were doubled [535 (465–666) vs 246 (211–288) min, P = 0.002] from an ex vivo lung reconditioning procedure as compared to conventional donors, respectively. At the end of the procedure, the PaO2/FiO2 ratio 224 (111–350) vs 324 (212–426) was lower for patients receiving from an ex vivo lung reconditioning donor as compared to patients receiving conventional donor lungs. However, the occurrence of Grade 3 PGD at 72 h [0 (0%) vs 11 (13%)] and the 1-month survival [13 (100%) vs 75 (90%)] or 1-year survival [13 (100%) vs 56 (77%)] were similar between ex vivo lung reconditioning and conventional donor lungs. No case of intraoperative recall was recorded. DISCUSSION In emphysema patients undergoing BLT, extubation in the OR followed by NIV was possible for half of the patients after combining thoracic epidural analgesia with total intravenous anaesthesia. Preoperative pulmonary hypertension, the grafts obtained after ex vivo lung conditioning, the requirement for intraoperative ECMO or major bleeding decreased the possibility of extubation in the OR. For patients extubated in the OR, the postoperative course or prognosis was not altered. Extubation in the OR after lung transplantation is considered as a goal for some teams [6–8], but the feasibility of extubation for emphysema patients after BLT has rarely been reported. In an observational study, we have reported extubation in the OR for 3 of 5 emphysema patients after BLT, and none of the patients were reintubated [9]. Other studies have reported only the feasibility of extubation after single-lung transplantation in emphysema patients. In a series of 6 patients, 2 were extubated in the OR [7]. In 91 patients, 53% were extubated in the OR, but 21% of these patients were reintubated [6]. In a series of 57 patients, 21 (37%) patients were extubated in the OR, and 2 (10%) patients were reintubated [8]. After BLT, the rate of extubation in the OR has been reported mainly in cystic fibrosis patients. Recently, a study of 89 cystic fibrosis patients undergoing BLT reported that 45 patients were extubated in the OR, and 4 were reintubated [15]. The success rate of early extubation was probably related to the systematic use of NIV [3]. Indeed, NIV is effective in improving gas exchange of either PaO2 or PaCO2 without sedation [16] after BLT [3]. Finally, the strategy for extubation in the OR was feasible without an increase in procedure duration (Table 2). The anaesthetic approach allowing for early extubation includes effective analgesia, normothermia, the use of short-acting anaesthetic drugs [5, 6, 17] and a skilled anaesthesiologist to maintain cardiorespiratory homeostasis continuously. In the absence of contraindication, thoracic epidural analgesia is the standard for postoperative pain control after bilateral thoracotomy: thoracic epidural analgesia decreases the duration of mechanical ventilation, the length of stay in the ICU and the rate of respiratory complication [18]. In this study, 4 patients without thoracic epidural analgesia were not extubated at the end of the procedure although they had met the criteria for extubation in the OR. Indeed, pain control after bilateral thoracotomy without epidural analgesia with a multimodal approach can induce sedation and respiratory depression. Epidural haematoma has never been described during lung transplantation, but a very low risk of haematoma exists [19]. The use of short-acting anaesthetic drugs needs continuous control and vigilance by the anaesthesiologist to avoid drug overdosing, thereby reducing side effects such as vasoplegia and vasopressor use [20]. The maintenance of anaesthesia was performed in all patients using an automated controller of total intravenous anaesthesia, allowing for the continuous titration of propofol and remifentanil guided by the electrocortical activity [13]. The protocol of our department was to use the controller systematically to reduce the workload [21] during this long and complicated procedure [9]. Extubation in the OR involves continuous interdisciplinary communication and cooperation among all members of the team. The need for ECMO was related to cardiopulmonary instability during the procedure and was associated with an increase in intraoperative bleeding (Table 2). Intraoperative instability as expected decreased the possibility of early extubation. For the anaesthesiologist, when the patient had an ECMO, the weaning from an assist device was prioritized over tracheal extubation. Intraoperative ECMO requirement and major bleeding have previously been reported to reduce the probability of early extubation in cystic fibrosis patients [15]. Ex vivo lung reconditioning [11] was used for rejected donor lungs with a low PaO2/FiO2 ratio and decreased extubation rate in the OR. While ischaemic graft duration is increased by the ex vivo procedure, there are no increase in the rate of Grade 3 PGD or one-year mortality as compared to conventional donors. This survival rate after the use of grafts provided by ex vivo lung reconditioning was similar to our experience [22]. As expected, postoperative ECMO requirement or the Grade 3 PGD [14] at 72 h were less frequent in the OR group. The criteria (PaO2/FiO2 ratio, chest radiograph or oedema) for extubation or for the evaluation of PGD are similar. These criteria at the end of the surgery in the OR were an early predictive marker of graft function, and the survival rate (Fig. 2) demonstrates that extubation in the OR seems to have no safety concerns. As also expected, extubation in the OR decreased mechanical ventilation duration, the length of stay in the ICU and the need for tracheotomy (Table 3). This association does not imply causality, but it was related to patient selection in the OR group. Finally, this strategy does not require additional ICU resources. Indeed, the need for critical care has dramatically increased due to the increase in candidates having ECMO before or after lung transplantation [23], and ICU resources are sometimes limited. The patients with Grade 3 PGD at 72 h (n = 11) received more packed red blood cells, fresh frozen plasma and colloid during the intraoperative period, while the rate of total intraoperative bleeding was similar. The increase in the intraoperative fluid administration has been reported as a factor associated with an increased rate of Grade 3 PGD [24]. Limitations This study is a retrospective analysis of a database from a single centre. It did not demonstrate that outcomes were different when the extubation was performed in the OR versus a few hours later in the ICU, when the patients had met the extubation criteria. Currently, the rate of emphysema patients extubated in the OR or within 24 h postoperatively after BLT has never been reported and remains unknown. The use of risk-adjustment methods (stratification, multivariate analysis, propensity score and so on) was not performed in this study. Indeed, the sample size was too small to perform a robust and accurate analysis. Over a 10-year period in a single institution, more than half of the adult emphysema patients could be extubated in the OR after BLT. This strategy involves a dynamic optimization of patient care, a rigorous selection of patients or grafts by skilled physicians and also close cooperation among all staff managing the candidates for lung transplantation. Extubation in the OR appears safe without the need for additional ICU resources in the postoperative period. ACKNOWLEDGEMENTS The authors thank Desmond McGlade, MBBS, FANZCA, Department of Anaesthesia, St. Vincent’s Hospital, Melbourne, Victoria, for his assistance on this article. Funding This work was supported by the Department of Anesthesiology, Hospital Foch, Suresnes, France, and Vaincre la Mucoviscidose, Paris France. Conflict of interest: Marc Fischler is the President of the Scientific Committee of MedSteer, which is a biomedical society promoting research and development of closed-loop tools. Ngai Liu is a cofounder of MedSteer, which is a biomedical society promoting research and development of closed-loop tools. 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Journal

European Journal of Cardio-Thoracic SurgeryOxford University Press

Published: May 23, 2018

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