The Number of Ventilator-free Days in the 28 Days Following LT
Conditions
Brief summary
In patients undergoing lung transplantation (LT), the investigators hypothesize that a systematic intraoperative ECMO strategy would reduce the need for invasive mechanical ventilation in the first 28 days without increasing adverse events, as compared to an on-demand intraoperative ECMO strategy. To date, LT remains a highly hazardous procedure. Even if the surgical procedure is well established, the intraoperative support is not, and most intra-operative ECMO decisions rely on local protocols, anesthesiologists' habits, and surgeons' preference. The efficacy of applying a systematic strategy on reducing the occurrence of severe primary graft dysfunction and thus mechanical ventilation in the 28 days following LT, without increasing mortality or morbidity, would support future guidelines on the use of ECMO in the intraoperative period of LT for obstructive and restrictive lung diseases.
Detailed description
Lung transplantation (LT) provides the prospect of improved survival and quality of life for patients with end stage lung and pulmonary vascular diseases. Its performance carries significant adverse effects, being either intra- or postoperative. The ventilation of a diseased lung for sometimes extended periods and the risk of reperfusion oedema and primary graft dysfunction is a challenge. Moreover, significant hemodynamic instabilities episodes might occur, because of pressure on, or displacement of the heart, clamping of the pulmonary arteries and ischemia-reperfusion syndrome. veno-arterial extracorporeal membrane oxygenation (VA-ECMO) has now replaced cardiopulmonary bypass for respiratory and hemodynamic intraoperative support, carrying less side effects, and an improved early survival. Even though ECMO is a widely used technique, no precise guideline exists on the hemodynamic and respiratory indexes in LT settings to initiate intraoperative ECMO, but only experts' opinion. Besides, it has to be underlined that the rate of LT performed in the absence of any mechanical support is highly variable among centres, ranging from being exceptional up to 70%. The investigators aim at evaluating two strategies of ECMO initiation in the pre- and intraoperative periods in patients with pulmonary disease requiring LT: an on-demand strategy, in which VA-ECMO will be initiated on high hemodynamic and respiratory needs thresholds and a systematic strategy in which VA-ECMO will be pre-emptively initiated. The investigators hypothesize that a systematic strategy allows to reduce the risk of severe primary graft dysfunction and the need for mechanical ventilator in the 28 days following LT without increasing adverse events
Interventions
Strategy would reduce the need for invasive mechanical ventilation in the first 28 days without increasing adverse events
Sponsors
Assistance Publique - Hôpitaux de Paris
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
SUPPORTIVE_CARE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Age \>18 years Assessed for bilateral sequential lung transplantation for obstructive or restrictive lung disease Affiliation to the French social security Written informed consent
Exclusion criteria
At listing : * a pulmonary hypertension with a mPAP \> 45 mmHg, including in the absence of haemodynamic collapse (MAP, LVEF, RV function all normal) * a pulmonary hypertension with echocardiographic evidences of right heart dysfunction (paradoxical septum or RV dilatation or RVEF \< 35%) * a pre-capillary pulmonary hypertension at right heart catheterization with low cardiac output * LT for primary pulmonary hypertension * LT for cystic fibrosis and graft-vs-host disease * Re-do LT * Combined multi-organ transplantation * Active malignancy * Pregnancy, breastfeeding * Patients under guardianship (tutelle, curatelle, sauvegarde de justice) Socondary
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| The number of ventilator-free days | The 28 days following LT | Assess the efficacy of a systematic, pre-operative VA-ECMO strategy on increasing ventilator-free days in the 28 days following LT |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| All-cause mortality | Day-90 after LT | — |
| Vital status | Day-90 after LT | — |
| Time-to-death from all causes | The first year after LT | — |
| The occurrence of ECMO-associated adverse event ; ECMO-associated adverse event defined as cannula infection, misplacement, intra-operative or per-ECMO air-embolism, limb ischemia, vascular complications, thrombophlebitis | The 28 days following LT, Assessed daily from day-1 to day-90 | — |
| The occurrence of ventilator associated pneumonia (VAP) ; Occurrence of VAP (microbiologically confirmed pneumonia occurring under invasive ventilation 21 and after 48 hours of invasive ventilation) | The 28 days following LT | — |
| The occurrence of intraoperative hemodynamic failure; | The 28 days following LT | Intra-operative amount of norepinephrine (dose in microg/kg of body weight) |
| The occurrence of post-operative hemodynamic failure ; | The 28 days following LT | Norepinephrine-free days (number of days without noradrenaline administration) |
| The occurrence of grade III PGD | The 72 hours following LT | — |
| The need of red blood cell transfusion | The 28 days following LT | Number of red blood cell packs administered |
| ECMO-free days ; VV or VA-ECMO-free days | The 28 days following LT | — |
| The length of intensive care unit stay | at day 90 | Length of ICU stay in days |
| The length of hospital stay; Length of hospital stay in days | at day 90 | — |
| The occurrence of bronchial complication requiring a bronchoscopic intervention ; Bronchial complications requiring a bronchoscopic intervention | From LT to 1-year | — |
| Forced expiratory volume during the first second (FEV1) | At 1-year | — |
| The occurrence of acute renal failure; | The 28 days following LT | Renal failure KDIGO stage 3 |
Countries
France
Contacts
Primary ContactJonathan MESSIKA, MD
Outcome results
None listed