Francois B, Cariou A, Clere-Jehl R, et al. Prevention of Early Ventilator-Associated Pneumonia after Cardiac Arrest. N Engl J Med. 2019;381:1831-1842.
To determine if prophylactic antibiotics affect the incidence of ventilator-associated pneumonia (VAP) in patients presenting with out-of-hospital post-cardiac arrest (OOHCA) with an initially shockable rhythm undergoing targeted temperature management at 32-34 degrees Celsius.
Patients with OOHCA who achieve ROSC are still plagued with high rates of morbidity and mortality. Targeted temperature management is often initiated prophylactically to attempt to mitigate neurologic morbidity; however, this intervention has been associated with increased risk of secondary infection, especially as it often conceals later-noticed symptoms of pneumonia (ie, fever, leukocytosis).1-2 50-60% of these patients will develop pneumonia during their ICU stay (whether from intra-arrest aspiration event or VAP), which has been associated with longer hospitalizations, ICU stays, and death.2-4 It has been hypothesized that prophylactic antibiotics for all OOHCA patients could improve morbidity and mortality by reducing rates of VAP.
198 randomized adults (>18 y/o) presenting with out-of-hospital post-cardiac arrest (OOHCA) with an initially shockable rhythm undergoing targeted temperature management at 32-34 degrees Celsius.
Exclusion criteria included non-shockable rhythm, in-hospital cardiac arrest, "moribund" patients (not defined in the paper), previous lung disease that could preclude interpretation of chest x-ray (also not defined in the paper), recent antibiotics therapy (including the week before arrest), pregnancy, colonization with multidrug-resistant bacteria, and known allergy to beta-lactam antibiotics.
Multicentered, randomized, double-blinded, placebo-controlled across 16 ICUs in France in patients hospitalized between August 2014 and September 2017.
Prophylactic antibiotic treatment with ampicillin-sulbactam 1200 mg IV TID for two days.
Placebo saline injections IV TID (amount not specified).
• Incidence of VAP within 7 days
• Development of VAP after 7 days during hospitalization
• Incidence of other nosocomial infections
• 28-day mortality
• Length of ICU stay
• Intestinal acquisition of multi-drug resistant bacteria
• Number of ventilator-free days until day 28
For the primary outcome, they found a lower incidence of early VAP in the treatment arm as opposed to control (19% v 34%; 95% CI 0.31 to 0.92; P=0.03). For all secondary outcomes, no statistically significant difference was found between the two groups. While they found significance in this primary outcome, they did not find a statistical difference in rate of VAP after 7 days, incidence of other nosocomial infections, 28-day mortality, or length of ICU stay.
The authors also included "supplementary material" that showed for 94 of the patients in each group for which data was available, the intervention group was associated with significantly lower cost compared to the control group.
• Good study design (multicenter, randomized, blind)
• Relevant question
• Very specific population (initiation of TTM, initial shockable rhythm, out-of-hospital cardiac arrest)
• Majority of OOHCA patients do not have shockable rhythm
• Difficulty in diagnosing VAP (initial diagnoses not always found to be accurate later, disagreement between two adjudicators)
Next time you achieve ROSC in a patient stable enough to transfer upstairs, giving prophylactic antibiotics should be on your algorithm of interventions to consider.
- Polderman K. Mechanisms of action, physiological effects, and complications of hypothermia. Crit Care Med. 2009;37(7 Suppl):S186-S202.
- Perbet S, Mongardon N, Dumas F, et al. Early-onset pneumonia after cardiac arrest: characteristics, risk factors and influence on prognosis. Am J Respir Crit Care Med. 2011;184(9):1048–1054.
- Tsai M-S, Chiang W-C, Lee C-C, et al. Infections in the survivors of out-of-hospital cardiac arrest in the first 7 days. Intensive Care Med. 2005;31(5):621–626.
- Hellenkamp K, Onimischewski S, Kruppa J, et al. Early pneumonia and timing of antibiotic therapy in patients after nontraumatic out-of-hospital cardiac arrest. Crit Care. 2016;20:31.