Inhaled amikacin versus placebo to prevent ventilator-associated pneumonia: the AMIKINHAL double-blind multicentre randomised controlled trial protocol.

INTRODUCTION: Pre-emptive inhaled antibiotics may be effective to reduce the occurrence of ventilator-associated pneumonia among critically ill patients. Meta-analysis of small sample size trials showed a favourable signal. Inhaled antibiotics are associated with a reduced emergence of antibiotic resistant bacteria. The aim of this trial is to evaluate the benefit of a 3-day course of inhaled antibiotics among patients undergoing invasive mechanical ventilation for more than 3 days on the occurrence of ventilator-associated pneumonia. METHODS AND ANALYSIS: Academic, investigator-initiated, parallel two group arms, double-blind, multicentre superiority randomised controlled trial. Patients invasively ventilated more than 3 days will be randomised to receive 20 mg/kg inhaled amikacin daily for 3 days or inhaled placebo (0.9% Sodium Chloride). Occurrence of ventilator-associated pneumonia will be recorded based on a standardised diagnostic framework from randomisation to day 28 and adjudicated by a centralised blinded committee. ETHICS AND DISSEMINATION: The protocol and amendments have been approved by the regional ethics review board and French competent authorities (Comité de protection des personnes Ouest I, No.2016-R29). All patients will be included after informed consent according to French law. Results will be disseminated in international scientific journals. TRIAL REGISTRATION NUMBERS: EudraCT 2016-001054-17 and NCT03149640.

High risk of pulmonary embolism in acute respiratory distress syndrome related to COVID-19: an observational controlled-cohort study.

BACKGROUND: COVID-19 may induce endovascular injury of pulmonary vessels and could be associated with increased risk of pulmonary embolism. The main objective was to compare the incidence of pulmonary embolism in patients with acute respiratory distress syndrome (ARDS) related to COVID-19 versus patients with pulmonary ARDS unrelated to COVID-19. METHODS: This is an observational controlled-cohort study performed at a single center of a university teaching hospital in France. The incidence of pulmonary embolism was prospectively assessed using computed tomography pulmonary angiography (CTPA) in patients with ARDS related to COVID-19 and compared to patients from a 3-year historical cohort of patients with pulmonary ARDS unrelated to COVID-19. In patients with ARDS related to COVID-19, CTPA was performed approximately 7 days after intubation or earlier in case of respiratory or hemodynamic worsening. RESULTS: CTPA was performed in 29 out of the 42 patients (69%) with ARDS related to COVID-19 and in 51 out of the 156 patients (33%) from the historical cohort of patients with pulmonary ARDS unrelated to COVID-19. Incidence of pulmonary embolism was 40% (17/42) in patients with ARDS related to COVID-19 and 3% (5/156) in the historical cohort (P=0.001). The proportion of patients with pulmonary embolism among all patients who had CTPA was 59% (17/29) in patients with ARDS related to COVID-19 and 10% (5/51) in the historical cohort (P=0.0001). After adjustment on the interval between ICU admission and computed tomography, COVID-19 remained independently associated with pulmonary embolism. CONCLUSIONS: Pulmonary embolism was particularly frequent in patients with ARDS related to COVID-19, thereby suggesting that CTPA should be systematically performed in these patients.