Protocol for venoarterial ExtraCorporeal Membrane Oxygenation to reduce morbidity and mortality following bilateral lung TransPlantation: the ECMOToP randomised controlled trial.

INTRODUCTION: Lung transplantation (LTx) aims at improving survival and quality of life for patients with end-stage lung diseases. Venoarterial extracorporeal membrane oxygenation (VA-ECMO) is used as intraoperative support for LTx, despite no precise guidelines for its initiation. We aim to evaluate two strategies of VA-ECMO initiation in the perioperative period in patients with obstructive or restrictive lung disease requiring bilateral LTx. In the control 'on-demand' arm, high haemodynamic and respiratory needs will dictate VA-ECMO initiation; in the experimental 'systematic' arm, VA-ECMO will be pre-emptively initiated. We hypothesise a 'systematic' strategy will increase the number of ventilatory-free days at day 28. METHODS AND ANALYSIS: We designed a multicentre randomised controlled trial in parallel groups. Adult patients with obstructive or restrictive lung disease requiring bilateral LTx, without a formal indication for pre-emptive VA-ECMO before LTx, will be included. Patients with preoperative pulmonary hypertension with haemodynamic collapse, ECMO as a bridge to transplantation, severe hypoxaemia or hypercarbia will be secondarily excluded. In the systematic group, VA-ECMO will be systematically implanted before the first pulmonary artery cross-clamp. In the on-demand group, VA-ECMO will be implanted intraoperatively if haemodynamic or respiratory indices meet preplanned criteria. Non-inclusion, secondary exclusion and VA-ECMO initiation criteria were validated by a Delphi process among investigators. Postoperative weaning of ECMO and mechanical ventilation will be managed according to best practice guidelines. The number of ventilator-free days at 28 days (primary endpoint) will be compared between the two groups in the intention-to-treat population. Secondary endpoints encompass organ failure occurrence, day 28, day 90 and year 1 vital status, and adverse events. ETHICS AND DISSEMINATION: The sponsor is the Assistance Publique-Hôpitaux de Paris. The ECMOToP protocol version 2.1 was approved by Comité de Protection des Personnes Ile de France VIII. Results will be published in international peer-reviewed medical journals. TRIAL REGISTRATION NUMBER: NCT05664204.

Circuit change during extracorporeal membrane oxygenation: single-center retrospective study of 48 changes.

BACKGROUND: Bleeding and thrombosis induce major morbidity and mortality in patients under extracorporeal membrane oxygenator (ECMO). Circuit changes can be performed for oxygenation membrane thrombosis but are not recommended for bleeding under ECMO. The objective of this study was to evaluate the course of clinical, laboratory, and transfusion parameters before and after ECMO circuit changes warranted by bleeding or thrombosis. METHODS: In this single-center, retrospective, cohort study, clinical parameters (bleeding syndrome, hemostatic procedures, oxygenation parameters, transfusion) and laboratory parameters (platelet count, hemoglobin, fibrinogen, PaO2) were collected over the seven days surrounding the circuit change. RESULTS: In the 274 patients on ECMO from January 2017 to August 2020, 48 circuit changes were performed in 44 patients, including 32 for bleeding and 16 for thrombosis. Mortality was similar in the patients with vs. without changes (21/44, 48% vs. 100/230, 43%) and in those with bleeding vs. thrombosis (12/28, 43% vs. 9/16, 56%, P = 0.39). In patients with bleeding, numbers of bleeding events, hemostatic procedures, and red blood cell transfusions were significantly higher before vs. after the change (P < 0.001); the platelet counts and fibrinogen levels decreased progressively before and increased significantly after the change. In patients with thrombosis, numbers of bleeding events and red blood cell transfusions did not change after membrane change. No significant differences were demonstrated between oxygenation parameters (ventilator FiO2, ECMO FiO2, and PaO2) and ECMO flow before vs. after the change. CONCLUSIONS: In patients with severe and persistent bleeding, changing the ECMO circuit decreased clinical bleeding and red blood cell transfusion needs and increased platelets and fibrinogen levels. Oxygenation parameters did not change significantly in the group with thrombosis.

Extubation Failure Prediction by Echography of the Diaphragm After Cardiothoracic Surgery: The EXPEDIA Study.

BACKGROUND: Successful extubation is difficult to predict. Ultrasound measurement of the diaphragm thickening fraction (DTF) might help predict weaning failure after cardiothoracic surgery. METHODS: We assessed the predictive performance of diaphragm ultrasound in a derivation cohort of 50 prospectively included cardiothoracic surgery subjects ready for a weaning trial and in a validation cohort of 39 subjects ventilated for ≥ 48 h. DTF was assessed by ultrasound during pressure support ventilation (PSV) then during a T-piece spontaneous breathing trial (SBT). DTF was the percentage change in diaphragm thickness between expiration and inspiration and DTFmax, the higher DTF value of the 2 hemidiaphragms. DTFmax during SBT (static study) and the difference in DTFmax between PSV and SBT (dynamic study) were analyzed. RESULTS: In the derivation cohort, DTFmax during SBT was 25.6 ± 17.3% in subjects with successful extubation and 65.2 ± 17.3% in those with weaning failure (difference 39.7 [95% CI 27.4-51.9], P < .01). During SBT, DTFmax ≥ 50% was associated with weaning failure (area under the receiver operating characteristic curve [AUC] 0.94 ± 0.05). In the dynamic study, a ≥ 40% DTFmax increase was associated with weaning failure (AUC 0.91 ± 0.06). In the validation cohort, DTFmax during SBT was 20.3 ± 17.1% in subjects with successful extubation and 82.0 ± 51.6% in those with weaning failure (difference 61.8 [95% CI 41.6-82.0], P < .01). During SBT, DTFmax ≥ 50% predicted weaning failure (AUC 0.99 ± 0.02). In the dynamic study, a ≥ 40% increase in DTFmax predicted weaning failure (AUC 0.81 ± 0.09). CONCLUSIONS: Measuring DTFmax during SBT and the DTFmax change when switching from PSV to SBT may help predict weaning failure after cardiothoracic surgery. The study was registered on ANZCTR. CLINICAL TRIAL REGISTRATION NUMBER: U1111-1180-1999.

Ex vivo perfusion of the donor heart: Preliminary experience in high-risk transplantations.

BACKGROUND: The number of heart transplantations (HTs) has decreased in France since 2017 (-5%/year) despite a stable rate of patients referred on the waiting list. Ex vivo heart perfusion (EVHP) is an innovative approach for organ preservation, reducing graft ischaemic time and facilitating continuous organ monitoring before transplantation. AIM: To report our preliminary experience of seven donor hearts preserved with EVHP, including the first heart resuscitated after circulatory-determined death in France. METHODS: Seven hearts were procured from donation after brain death (DBD) for HT or donation after circulatory-determined death (DCD) for research purposes (Protocol PFS20-004, Agence de la Biomédecine, La Plaine Saint-Denis, France). All grafts were preserved using the Organ Care System® (TransMedics Inc., Andover, MA, USA) for normothermic EVHP. Perfusion parameters were adjusted to achieve stable or decreasing arterial lactate trend consistent with suitability for organ transplantation. RESULTS: Indications for EVHP were assessment of a marginal graft in four cases, prolonged preservation in two cases (anticipated duration for retrieval of recipient's heart>3hours) and resuscitation after circulatory-determined death in one case. Median duration of EVHP was 270 (interquartile range 216-343) minutes. five were transplanted, with a median ex situ preservation time (ischaemic time+EVHP time) of 334 (interquartile range 326-444) minutes. The two other grafts were discarded for HT. Three recipients had extracorporeal life support after HT, and presented complete cardiac recovery within a week after HT. One patient died at day 11 because of septic shock. The 3-month survival rate was 75% among recipients. Three months after HT, the left ventricular ejection fraction was>60% in all cases. CONCLUSIONS: EVHP enabled safe prolonged preservation and assessment of marginal grafts. This approach provides an opportunity to expand the donor pool by resuscitating grafts from donors with extended criteria, including controlled DCD.

Prognostic value of the PaO2 /FiO2 ratio determined at the end-surgery stage of a double-lung transplantation.

INTRODUCTION: We evaluated the prognostic role of the arterial oxygen partial pressure/fractional inspired oxygen ratio (PaO2 /FiO2 ratio) measured at the end of double-lung transplantation (DLT). METHODS: This was a monocentric cohort study of all consecutive DLT patients between January 1, 2012, and January 1, 2016, except patients with preoperative extracorporeal membrane oxygenation (ECMO), intraoperative cardiopulmonary bypass, postoperative ECMO, large patent foramen ovale, redo transplantation during the study period, and multiorgan transplantation. RESULTS: A total of 164 patients were included in the study; 45 had a PaO2 /FiO2 ratio <200, 39 a ratio in the range 200-300, and 80 a ratio >300. The risk of being in the lower ratio group is positively related to body mass index, preoperative pulmonary hypertension, and fibrosis. It is negatively related to emergency surgery, age, and intraoperative institution of ECMO. There was a trend for more grade 3 pulmonary graft dysfunction at day 3 in the worst PaO2 /FiO2 ratio group. Mortality at 1000 days was similar for all patients and even after exclusion of patients who had required intraoperative ECMO. CONCLUSION: PaO2 /FiO2 ratio measured at the end of DLT does not forecast 1000-day mortality.

Inhaled nitric oxide dependency at the end of double-lung transplantation: a boosted propensity score cohort analysis.

Inhaled nitric oxide (iNO) is usually used during lung transplantation despite controversial postoperative benefits. Our group chose to administer iNO systematically during the procedure and stop at the end of surgery. This study aims to describe the features of patients who cannot be weaned from iNO, the reasons for this and its impact on postoperative outcomes. This is a monocentric cohort study comprised all consecutive patients who underwent double-lung transplantation (DLT) between 1 January 2012 and 1 January 2016. The impact of iNO dependency on postoperative outcomes was estimated using a boosted inverse probability of treatment weighting estimator. A total of 9.8% of the 173 patients included in the study could not be weaned from iNO at end-surgery stage. Body mass index (OR = 2.03, 95% CI = 1.14-3.29, P = 0.02) and intraoperative extracorporeal membrane oxygenation (OR = 1.80, 95% CI = 1.02-2.72, P = 0.04) were risk factors for iNO dependency In the weighted population, iNO dependency was associated with an increased prevalence of grade 3 primary graft dysfunction (adjusted RR = 4.20, 95% CI = 1.75-10.09, P < 0.001) and decreased postoperative survival during the first 1500 days of follow-up (adjusted HR = 5.0, 95% CI = 1.86-13.48, P < 0.001). Inhaled nitric oxide dependency is an early marker of a poor prognosis following DLT.