Title: Prevention of Early Ventilator-Associated Pneumonia after Cardiac Arrest
Author: Bruno Franois, M.D.,, Alain Cariou, M.D., Ph.D.,, Raphal Clere-Jehl, M.D.,, Pierre-Franois Dequin, M.D., Ph.D.,, Franoise Renon-Carron, Pharm.D.,, Thomas Daix, M.D.,, Christophe Guitton, M.D., Ph.D.,, Nicolas Deye, M.D., Ph.D.,, Stéphane Legriel, M.D.,, Gatan Plantefève, M.D.,, Jean-Pierre Quenot, M.D.,, Arnaud Desachy, M.D.,, Toufik Kamel, M.D.,, Sandrine Bedon-Carte, M.D.,, Jean-Luc Diehl, M.D.,, Nicolas Chudeau, M.D.,, Elias Karam, M.D.,, Isabelle Durand-Zaleski, M.D., Ph.D.,, Bruno Giraudeau, Ph.D.,, Philippe Vignon, M.D., Ph.D.,, and Amélie Le Gouge, M.Sc.
Patients who are treated with targeted temperature management after out-of-hospital cardiac arrest with shockable rhythm are at increased risk for ventilator-associated pneumonia. The benefit of preventive short-term antibiotic therapy has not been shown.
We conducted a multicenter, double-blind, randomized, placebo-controlled trial involving adult patients (>18 years of age) in intensive care units (ICUs) who were being mechanically ventilated after out-of-hospital cardiac arrest related to initial shockable rhythm and treated with targeted temperature management at 32 to 34°C. Patients with ongoing antibiotic therapy, chronic colonization with multidrug-resistant bacteria, or moribund status were excluded. Either intravenous amoxicillin–clavulanate (at doses of 1 g and 200 mg, respectively) or placebo was administered three times a day for 2 days, starting less than 6 hours after the cardiac arrest. The primary outcome was early ventilator-associated pneumonia (during the first 7 days of hospitalization). An independent adjudication committee determined diagnoses of ventilator-associated pneumonia.
A total of 198 patients underwent randomization, and 194 were included in the analysis. After adjudication, 60 cases of ventilator-associated pneumonia were confirmed, including 51 of early ventilator-associated pneumonia. The incidence of early ventilator-associated pneumonia was lower with antibiotic prophylaxis than with placebo (19 patients [19%] vs. 32 [34%]; hazard ratio, 0.53; 95% confidence interval, 0.31 to 0.92; P=0.03). No significant differences between the antibiotic group and the control group were observed with respect to the incidence of late ventilator-associated pneumonia (4% and 5%, respectively), the number of ventilator-free days (21 days and 19 days), ICU length of stay (5 days and 8 days if patients were discharged and 7 days and 7 days if patients had died), and mortality at day 28 (41% and 37%). At day 7, no increase in resistant bacteria was identified. Serious adverse events did not differ significantly between the two groups.
A 2-day course of antibiotic therapy with amoxicillin–clavulanate in patients receiving a 32-to-34°C targeted temperature management strategy after out-of-hospital cardiac arrest with initial shockable rhythm resulted in a lower incidence of early ventilator-associated pneumonia than placebo. No significant between-group differences were observed for other key clinical variables, such as ventilator-free days and mortality at day 28.