Initial trophic vs full enteral feeding in patients with acute lung injury: the EDEN randomized trial

Abstract

Context: The amount of enteral nutrition patients with acute lung injury need is unknown.

Objective: To determine if initial lower-volume trophic enteral feeding would increase ventilator-free days and decrease gastrointestinal intolerances compared with initial full enteral feeding.

Design, setting, and participants: The EDEN study, a randomized, open-label, multicenter trial conducted from January 2, 2008, through April 12, 2011. Participants were 1000 adults within 48 hours of developing acute lung injury requiring mechanical ventilation whose physicians intended to start enteral nutrition at 44 hospitals in the National Heart, Lung, and Blood Institute ARDS Clinical Trials Network.

Interventions: Participants were randomized to receive either trophic or full enteral feeding for the first 6 days. After day 6, the care of all patients who were still receiving mechanical ventilation was managed according to the full feeding protocol.

Main outcome measures: Ventilator-free days to study day 28.

Results: Baseline characteristics were similar between the trophic-feeding (n = 508) and full-feeding (n = 492) groups. The full-feeding group received more enteral calories for the first 6 days, about 1300 kcal/d compared with 400 kcal/d (P < .001). Initial trophic feeding did not increase the number of ventilator-free days (14.9 [95% CI, 13.9 to 15.8] vs 15.0 [95% CI, 14.1 to 15.9]; difference, -0.1 [95% CI, -1.4 to 1.2]; P = .89) or reduce 60-day mortality (23.2% [95% CI, 19.6% to 26.9%] vs 22.2% [95% CI, 18.5% to 25.8%]; difference, 1.0% [95% CI, -4.1% to 6.3%]; P = .77) compared with full feeding. There were no differences in infectious complications between the groups. Despite receiving more prokinetic agents, the full-feeding group experienced more vomiting (2.2% vs 1.7% of patient feeding days; P = .05), elevated gastric residual volumes (4.9% vs 2.2% of feeding days; P < .001), and constipation (3.1% vs 2.1% of feeding days; P = .003). Mean plasma glucose values and average hourly insulin administration were both higher in the full-feeding group over the first 6 days.

Conclusion: In patients with acute lung injury, compared with full enteral feeding, a strategy of initial trophic enteral feeding for up to 6 days did not improve ventilator-free days, 60-day mortality, or infectious complications but was associated with less gastrointestinal intolerance.

Trial registration: clinicaltrials.gov Identifiers: NCT00609180 and NCT00883948.

Figure 1

Enrollment, Randomization, and Follow-up ^aPatients may have had more than 1 exclusion criterion.

Figure 2

Full-Feeding Protocol Left side indicates actions to be taken for gastric residual volumes greater than 400 mL; right side advances enteral feeding every 6 hours to goal rates as long as gastrointestsinal intolerances are not present.

Figure 3

Survival and Hospital Discharge Percentages were calculated daily; the denominator at all times represents all patients in each group with the exception of 1 patient in the full-feeding group who was lost to follow-up and censored in these plots at day 36. The solid lines represent the proportion of patients surviving at each time; dashed lines represent the proportion of patients discharged from the hospital at each time. The areas above the solid lines represent the proportion of patients who have died in each group at each time; the areas below the dashed lines represent the proportion of patients alive and discharged from the hospital at each time. Areas between the solid and dashed lines represent the proportion of patients alive but still hospitalized in each group at each time.

Figure 4

Daily Energy Intake and Daily Percentage of Goal Enteral Feedings Sample sizes reflect numbers of patients with available data still receiving mechanical ventilation and enteral feeding on each day. A, Randomization occurred on day 0. Error bars represent 95% CIs. P<.001 at days 1, 2, 3, 4, 5, and 6; P=.03 at day 9. B, Randomization occurs on day 0. Error bars represent 95% CIs. P<.001 at days 1, 2, 3, 4, 5, and 6.

Figure 5

Daily Gastrointestinal Intolerances Percentage of patients on each study day meeting at least 1 gastrointestinal intolerance criterion. Sample sizes reflect numbers of patients with at least 1 intolerance and still receiving mechanical ventilation and enteral feeding. Error bars represent 95% CIs. P < .001 at days 2 and 3.

Figure 6

Mean 8 am Plasma Glucose and Insulin Infusion Rates A, Day 0 glucose values are baseline. To convert values to mmol/L, multiply by 0.0555. Three patients in the trophic-feeding group did not have recorded baseline glucose measurements. Error bars represent 95% CIs. P<.001 at days 1, 2, 3, 4, and 5; P=.04at day 6; P=.02 at day 7. B, Sample sizes reflect numbers of patients receiving insulin infusion. Error bars represent 95% CIs. P<.001 at days 1,2,3, 4, 5, 6, and 7.

Figure 7

Cumulative Net Fluid Balance Sample sizes reflect numbers of patients with cumulative fluid balance data collected for the shorter of 7 days or until they were no longer receiving mechanical ventilation. The trophic-feeding group had significantly lower net cumulative fluid balance on study days 2 through 7 compared with the full-feeding group. Error bars represent 95% CIs. P= .02 at day 3; P < .001 at days 4, 5, and 6; P=.01 at day 7.