Objective Enteral nutrition is provided to mechanically ventilated patients who cannot eat normally, yet the amount of support needed is unknown. We conducted this randomized, open-label study to test the hypothesis that initial low-volume (i.e. trophic) enteral nutrition would decrease episodes of gastrointestinal intolerance/complications and improve outcomes as compared to initial full-energy enteral nutrition in patients with acute respiratory failure. Design Randomized, open-label study Patients 200 Patients with acute respiratory failure expected to require mechanical ventilation for at least 72 hours Interventions Patients were randomized to receive either initial trophic (10 ml/hr) or full-energy enteral nutrition for the initial 6 days of ventilation. Measurements and Main Results The primary outcome measure was ventilator-free days to day 28. Baseline characteristics were similar between the 98 patients randomized to trophic and the 102 patients randomized to full-energy nutrition. At enrollment, patients had a mean APACHE II score of 26.9, PaO2/FiO2 of 182 and 38% were in shock. Both groups received similar duration of enteral nutrition (5.5 vs. 5.1 days; P=0.51). The trophic group received an average of 15 ± 11% of goal calories daily through day 6 compared to 74.8 ± 38.5% (P<0.001) for the full-energy group. Both groups had a median of 23.0 ventilator-free (P=0.90) and 21.0 ICU-free days (P=0.64). Mortality to hospital discharge was 22.4% for trophic vs. 19.6% for full-energy (P=0.62). In the first 6 days, the trophic group had trends for less diarrhea (19 vs. 24% of feeding days; P=0.08) and significantly fewer episodes of elevated gastric residual volumes (2 vs. 8% of feeding days; P<0.001). Conclusions Initial trophic enteral nutrition resulted in similar clinical outcomes in mechanically ventilated patients with acute respiratory failure as early full-energy enteral nutrition but with fewer episodes of gastrointestinal intolerance.

Objective: A high plasma level of inflammasome mediator interleukin-18 was associated with mortality in observational acute respiratory distress syndrome cohorts. Statin exposure increases both inflammasome activation and lung injury in mouse models. We tested whether randomization to statin therapy correlated with increased interleukin-18 in the ARDS Network Statins for Acutely Injured Lungs from Sepsis trial. Design: Retrospective analysis of randomized controlled clinical trial. Setting: Multicenter North American clinical trial, the ARDS Network Statins for Acutely Injured Lungs from Sepsis. Patients: Six hundred eighty-three subjects with infection-related acute respiratory distress syndrome, representing 92% of the original trial population. Interventions: Random assignment of rosuvastatin or placebo for up to 28 days or 3 days after ICU discharge. Measurements and Main Results: We measured plasma interleukin-18 levels in all Statins for Acutely Injured Lungs from Sepsis patients with sample available at day 0 (baseline, n = 683) and day 3 (after randomization, n = 588). We tested the association among interleukin-18 level at baseline, rising interleukin-18, and the impact of statin therapy on 60-day mortality, adjusting for severity of illness. Baseline plasma interleukin-18 level greater than or equal to 800 pg/mL was highly associated with 60-day mortality, with a hazard of death of 2.3 (95% CI, 1.7–3.1). Rising plasma interleukin-18 was also associated with increased mortality. For each unit increase in log2 (interleukin-18) at day 3 compared with baseline, the hazard of death increased by 2.3 (95% CI, 1.5–3.5). Subjects randomized to statin were significantly more likely to experience a rise in plasma interleukin-18 levels. Subjects with acute kidney injury, shock, low baseline interleukin-18, and those not receiving systemic corticosteroids were more likely to experience rising interleukin-18. Randomization to statin therapy was associated with rising in interleukin-18 in all of those subsets, however. Conclusions: Elevated baseline plasma interleukin-18 was associated with higher mortality in sepsis-induced acute respiratory distress syndrome. A rise in plasma interleukin-18 was also associated with increased mortality and was more common in subjects randomized to statin therapy in this clinical trial.