Prevention of Early Ventilator-Associated Pneumonia after Cardiac Arrest

Bruno François, Alain Cariou, Raphaël Clere-Jehl et el published a trial of  intravenous amoxicillin-clavulanate versus placebo  in patients undergoing  targeted temperature management and mechanical ventilation for out of hospital cardiac arrest  with shockable rhythm.

BACKGROUND

 Targeted temperature management remains  cornerstone of therapy for  out of hospital cardiac arrest.  however targeted temperature management is associated with increased risk of secondary infections,  mainly early ventilator associated pneumonia.  A study showing benefit of cefuroxime in patients with coma was published in 1997.  A smaller study failed to show any benefit of amoxicillin/ clauvunate in preventing ventilator associated pneumonia. Following this,  there were smaller single center studies or retrospective studies only.

WHERE

It was a multi Center double blind randomized placebo controlled trial  involving adult patients  in 16 ICUs in France( teaching and non teaching hospitals).

WHO

198 patients,  18 years of age or older hospitalized in ICU after out  of hospital cardiac arrest  with shockable rhythm  undergoing treatment  with targeted temperature management( 32-34 degrees C) and mechanical ventilation.

Exclusion criteria were patients with non shockable rhythm,  in hospital cardiac arrest,  ongoing pneumonia or gross aspiration, presence of  infiltrates on chest x-ray  on admission,  previous lung disease, pregnancy, ongoing antibiotic use, known allergy to penicillin, moribund status.

INTERVENTION

Patients in antibiotics group received 2 days   of  intravenous amoxicillin clavulanate (1 g and 200 mg) 3 times a day.

DIAGNOSIS OF VENTILATOR ASSOCIATED PNEUMONIA

Using 2010 definition by FDA, based on Clinical Pulmonary Infection Score(score more than 6) and Sequential Organ Failure Assessment score were assessed, and bedside anteroposterior chest radiography, arterial blood gas analysis, blood cultures, and quantitative sampling of the lower respiratory tract (by either bronchoalveolar lavage or endotracheal aspiration).

Clinical criteria were documented fever or hypothermia (with fever defined as an oral or tympanic temperature
≥38°C and hypothermia defined as a core body temperature <35°C), an abnormal total peripheral white-cell count (>10,000 per cubic millimeter or >15% immature neutrophils [bands], regardless of white-cell count, or leukopenia
with a white-cell count <4500 per cubic millimeter), new-onset purulent sputum or change in the character of sputum.

OUTCOMES

Primary outcome was the onset of early ventilator-associated pneumonia (during the first 7 days of hospitalization).

Secondary outcomes were late ventilator-associated pneumonia (after day 7 of hospitalization through ICU discharge or death), other nosocomial infections (bloodstream and urinary tract infections), mortality at day 28,
intestinal acquisition of multidrug-resistant bacteria on day 7 ,  length of stay in the ICU, number of ventilator-free days until day 28, and costs consequence analysis.

RESULTS

  1. 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).
  2. 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%).
  3. At day 7, no increase in resistant bacteria was identified.
  4. Serious adverse events did not differ significantly between the two groups.

BOTTOMLINE

Prophylactic amoxicillin clavulanate can  reduce the incidence of  early ventilator associated pneumonia  in patient’s treated with targeted temperature management for shockable out of hospital cardiac arrest.  However it did not improve mortality or had any impact on length of stay.   Prophylactic antibiotic did not change the resistant pattern and adverse events were not different.