In this episode, I’ll discuss inhaled amikacin to prevent VAP.
The prevention of ventilator associated pneumonia has been a focus of research for many decades. The peak incidence of VAP appears to occur after about 7 days of ventilator use and this has led researchers to focus on whether there is a point before this 7 day mark when progression to VAP can be hindered by antibiotics.
Authors recently published in New England Journal of Medicine results of a multi-center randomized controlled trial on the use of inhaled amikacin to prevent VAP.
850 critically ill adult patients who had been undergoing invasive mechanical ventilation for at least 72 hours were assigned to receive inhaled amikacin at a dose of 20 mg/kg of ideal body weight once daily or to receive placebo for 3 days.
At 28 days the incidence of VAP was 15% in the amikacin group compared to 22% in the placebo group. This equated to a statistically significant difference in restricted mean survival time to ventilator-associated pneumonia of 1.5 days in favor of the amikacin group. Infection-related ventilator-associated complications were also significantly lower in the amikacin group with a hazard ratio of 0.66.
Out of the patients who did not have acute kidney injury at the time they entered the study, AKI developed by day 28 in 4% of the amikacin group and in 8% of the placebo group patients. While this is counter-intuitive to what would be expected from patients who received an aminoglycoside, the upper range of the 95% confidence interval excluded 1.
The authors concluded:
Among patients who had undergone mechanical ventilation for at least 3 days, a subsequent 3-day course of inhaled amikacin reduced the burden of ventilator-associated pneumonia during 28 days of follow-up.
This is a large multicenter high quality randomized trial and may eventually result in a widespread change in practice to using inhaled amikacin to prevent VAP. However the need to continue to study this intervention continues as the authors point our there is reason to believe a start after 4 or 5 days of ventilation rather than the 3 used in this study may be reasonable, and this trial was not powered to assess differences in death or length of ICU and hospital stay.
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