Short-Acting Sedative-Analgesic Drugs Protect Against Development of Ventilator-Associated Events in Children: Secondary Analysis of the EUVAE Study

BACKGROUND: The U.S. Centers for Disease Control and Prevention proposed a shift in its surveillance paradigm from ventilator-associated pneumonia to ventilator-associated events (VAE) to broaden the focus of prevention and achieve a greater impact on outcomes. The main objective of the present study was to identify factors associated with pediatric VAEs in children undergoing mechanical ventilation ≥ 48 h.

METHODS: This was a secondary analysis of a pediatric cohort of a multicenter prospective study. Children who underwent mechanical ventilation ≥ 48 h were included. Exclusion criteria were previous ventilation, extracorporeal life support, and right-to-left shunt or pulmonary hypertension. In the subjects with multiple episodes of mechanical ventilation, only the first episode was considered. Remifentanil and propofol are classified as short-acting sedative and analgesic agents. Pediatric VAE is defined as an “increase in PEEP ≥ 2 cm of H₂O, an increase in _FIO2 of 0.20, or an increase in _FIO2 of 0.15 plus an increase in PEEP ≥ 1 cm of H₂O sustained for ≥1 d. Associations with pediatric VAE were estimated through multivariate Cox proportional hazards analysis. Hazard ratios and 95% CI were computed.

RESULTS: In a cohort of 90 children, 24 pediatric VAEs were documented in 906 ventilator-days. Pediatric VAEs developed after a median of 4.5 (interquartile range, 4–7.25) d. Surgical admissions, spontaneous breathing trials, early mobility, vasopressors, red blood cell units transfusion, type of sedation (continuous vs intermittent), benzodiazepine use for >3 d, and pharmacologic paralysis were not associated with pediatric VAE, whereas the use of continuous short-acting sedative-analgesic agents was identified as a strong protective factor against pediatric VAE (hazard ratio 0.06 [95% CI 0.007–0.5]).

CONCLUSIONS: Treatment with short-acting sedative-analgesic agents should be preferred for sedation of mechanically ventilated children in intensive care.