Effects of daily treatment with acid suppressants for stress ulcer prophylaxis on risk of ventilator-associated events

Objective: To estimate the effects of continuous daily treatment with different acid suppressants on the risk of ventilator-associated events in critically ill patients. Design: Retrospective cohort study. Patients: Adult critically ill patients who underwent mechanical ventilation for >= 3 days during an inpatient admission between January 2006 and December 2014. Methods: We estimated the 30-day cumulative risk ratios (RRs) for ventilator-associated events comparing daily proton pump inhibitor (PPI) versus daily histamine-2-receptor antagonist (H(2)RA) strategies while controlling for time-fixed and time-varying confounding and accounting for competing events. Results: Of 6,133 patients, on ventilation day 3, 58.8% received H2RAs, 26.1% received PPIs, and 4.1% received sucralfate. Patients frequently changed treatment throughout follow-up. Among 4,595 patients receiving PPIs or H2RAs on day 3, we found no differences in risk estimates for ventilator mortality and extubation alive comparing daily PPI versus daily H(2)RA strategies: RR, mortality, 1.03 (95% CI, 0.89-1.22); extubation alive, 1.00 (95% CI, 0.96-1.03). We found similar results after accounting for PPI dose. For possible ventilator-associated pneumonia (PVAP) and infection-related ventilator-associated complication (IVAC), point estimates were larger, but the 95% CIs crossed 1.0: RR PVAP, 1.25 (95% CI, 0.80-1.94); IVAC, 0.89 (95% CI, 0.64-1.17). The magnitude of effect estimates depended on PPI dose. The RR for PVAP, high-dose PPI versus H(2)RA, was 1.53 (95% CI, 0.82-2.51), and for low-dose PPI versus H(2)RA, the RR was 0.97 (95% CI, 0.47-1.63). For IVAC, high-dose PPI versus H(2)RA, the RR was 1.01 (95% CI, 0.66-1.42), and for low-dose PPI versus H(2)RA, the RR was 0.78 (95% CI, 0.50-1.11). Conclusions: We estimated no effect of daily PPI versus daily H(2)RA on risk of mortality or extubation alive in critically ill patients. Further investigation with larger samples is warranted for PVAP and IVAC.