Pneumonia are the most frequent infectious complication in patients on Extracorporeal Membrane Oxygenation Veno-arterial (ECMO-VA), with a treatment failure rate of around 40%, even though antibiotic therapy is tailored to the germs identified. One hypothesis to explain this particularly high failure rate is the reduced pulmonary blood flow associated with ECMO offloading of the heart. Although there are no data to date on the pulmonary penetration of antibiotics in patients undergoing VA-ECMO, this phenomenon of pulmonary hypoperfusion could contribute to altering the alveolocapillary diffusion of antibiotics, thereby reducing their concentration in the pulmonary parenchyma.
Our hypothesis is that amikacin nebulization could increase bacterial clearance and, ultimately, limit treatment failure or recurrence of gram-negative bacilli (GNB) pneumonia in patients undergoing VA-ECMO.
Patient 18 years or older
Circulatory assistance by veno-arterial ECMO for at least 24 hours prior to documentation of pneumonia
Invasive mechanical ventilation
Diagnostic suspicion of pneumonia based on evocative criteria (presence of at least 2 of the following criteria): fever (superior to 38. 5°C), hypothermia (inferior to 36.0°C), hyperleukocytosis (superior to 11 × 10^9 l-1) or leukopenia (inferior to 4 × 10^9 l-1), purulent tracheobronchial secretions, altered oxygenation with need to increase FiO2 on ECMO or ventilator for the same SaO2 or PaO2 target, new or persistent pulmonary infiltrate(s) on chest x-ray in bed, or image suggestive of pneumonia on chest CT, or consolidation of appearance suggestive of an infectious origin on pulmonary ultrasound.
Known allergy to amikacin or another aminoglycoside or to an auxiliary drug or to any of their excipients.
Contraindication to the administration of amikacin or its excipients listed in the summary of product characteristics.
Contraindication to the administration of an auxiliary drug or to one of its excipients listed in the summary of product characteristics.
Contraindications to nebulization
Parallel
Amikacin
DrugPatients included in the inhaled amikacin group will receive inhaled antibiotic therapy by nebulization of amikacin at a dose of 25 mg/kg in 1 daily dose (+/- 3 hours apart), within 6 hours of randomization and for a total duration of 5 days.
Standard of care
DrugPatients included in the standard of care group will not receive any nebulization. They will receive Standard care alone.
Bacterial eradication rate
Bacterial eradication rate, defined as absence of germs on direct examination and negative culture of a tracheal aspirate taken on day 5 (D5) after randomization and at least 12 hours after the last administration of inhaled amikacin.
Clinical cure rate
Clinical cure rate, defined as disappearance of clinical signs suggestive of pneumonia, biological inflammatory syndrome and correction of haematosis disorders, at D5.
Pneumonia persistence rate
Pneumonia persistence rate defined as the presence of the pathogen identified at a significant level on culture of tracheal aspirate at D5.
Change in clinical pulmonary infection score (CPIS)
Difference between CPIS score at D5 and CPIS score at randomization.
Change in pulmonary aeration score
Difference between ultrasound pulmonary aeration score at D5 and pulmonary aeration score at randomization.
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