Abstract & Commentary
ICU Feeding Strategy and Acute Lung Injury Outcomes
By Betty Tran, MD, MS
Assistant Professor of Medicine, Pulmonary and Critical Care Medicine, Rush University Medical Center, Chicago
Dr. Tran reports no financial relationships relevant to this field of study.
SYNOPSIS: Survivors of acute lung injury (ALI) performed below predicted values on a number of physical and cognitive performance assessments at 6 and 12 months. Initial trophic vs full enteral feeding during the first 6 days of mechanical ventilation had no significant effect on these long-term outcomes.
- SOURCE: Needham DM, et al. Physical and cognitive performance of acute lung injury patients one year after initial trophic vs full enteral feeding: EDEN trial follow-up. Am J Respir Crit Care Med 2013;188:567-576.
The EDEN trial was a multicenter, randomized, open-label study that sought to compare the effect of initial trophic vs full enteral feeding for the first 6 days of mechanical ventilation on clinical outcomes of patients with acute lung injury (ALI).1 Inclusion criteria included patients with ALI (defined by the presence of bilateral pulmonary infiltrates, PaO2/FiO2 < 300 mmHg, and the absence of left atrial hypertension) within 48 hours of onset, on mechanical ventilation for less than 72 hours, who were eligible for enteral feeding. Despite achieving a marked difference in total protein and caloric intake between the trophic and full feeding groups within 6 days of randomization (400 vs 1300 kcal/day), the investigators found no significant difference in short-term outcomes such as ventilator-free days or 60-day mortality. In this ancillary study, Needham and colleagues sought to assess longer-term physical and cognitive outcomes of ALI survivors at 6 and 12 months and the effect of initial trophic vs full enteral feeding on the same outcomes.
After excluding patients with baseline cognitive impairment, who were non-English speakers, homeless, or < 18 years of age, 174 patients with ALI from 12 hospitals participated in a series of physical and cognitive tests at 6 and 12 month follow-up. The primary physical performance outcome was the 12-month 6-minute walk test (6MWT) as a percent of the predicted value; a number of secondary physical outcomes were also assessed. The primary outcome for cognitive performance was the presence of "cognitive impairment" at 12 months, defined as having either one cognitive test with a score ≥ 2 standard deviations (SD) or at least two tests with a score ≥ 1.5 SD below population norms. A battery of cognitive tests that constituted individual secondary outcomes evaluated executive function, language, immediate and delayed memory, verbal reasoning and concept formation, and attention and working memory.
The mean 6MWT at 12 months was 66% predicted (± 25%) with overall small but statistically significant improvements in most physical performance parameters from 6- to 12-month follow-up. At 12 months, 25% of ALI survivors had cognitive impairment, which was a significant improvement from 36% at 6 months (P = 0.001). In all cognitive tests except Digit Span (evaluates attention and working memory), there was also significant improvement in mean scores between 6 and 12 months.
When patients who were randomized to initial trophic enteral feeds were compared to those receiving full feeds, there was no significant difference in mean percent predicted 6MWT values (63% [± 25%] vs 70% [± 24%], P = 0.146), proportion of patients with cognitive impairment (29% vs 20%, P = 0.311), or in all secondary outcomes at 12 months even after adjustment for multiple covariates.
There were several notable strengths in this trial. Sample size was relatively robust compared to prior studies involving long-term outcomes in ALI survivors. A detailed battery of physical and cognitive testing was performed in-person by trained personnel who were blinded to each patient’s treatment allocation. Concerted efforts resulted in a minimal loss to follow-up. A priori statistical plans were formulated to attempt to minimize confounding and effect modification by several other variables. Known ICU interventions that have been shown to improve outcomes were employed across the board, including ARDSNet lung protective ventilation, fluid-conservative management strategies, and targeted blood glucose control. Overall, ALI survivors had small physical and cognitive improvements over time, but still performed below expected on physical and cognitive testing 1 year after ALI onset regardless of the average protein and total caloric intake they received early in their ICU course.
This study contributes to our growing but still limited knowledge on the optimal timing, formulation, and amount of nutrition in the ICU. Rapid muscle catabolism related to systemic inflammation with the potential to cause muscle atrophy and severe nutritional deficits has been described in early critical illness.2 However, whether nutrition can modify these processes and via what mechanisms is not known. We have yet to show a nutritional intervention in this acute phase that can alter these effects and result in improved short- or long-term patient outcomes. In one such attempt, the Omega study, supplementation with omega-3 fatty acids, γ-linolenic acid, and other antioxidants that could theoretically modulate the systemic inflammatory response not only resulted in no patient benefit but was associated with more days on the ventilator, in the ICU, and organ failure.3 As we continue to expand our understanding of risk factors and treatment strategies that have an impact on long-term outcomes in survivors of ALI and critical illness, it is likely that nutrition is but one aspect in the overall trajectory of recovery for these patients. It will be interesting to see how important a role it plays in comparison to other interventions such as early physical and occupational therapy and minimizing sedation and delirium.
1. The National Heart, Lung, and Blood Institute Acute Respiratory Distress Syndrome (ARDS) Clinical Trials Network. Initial trophic vs full enteral feeding in patients with acute lung injury. JAMA 2012; 307:795-803.
2. Batt J, et al. Intensive care unit-acquired weakness: Clinical phenotypes and molecular mechanisms. Am J Respir Crit Care Med 2013;187:238-246.
3. Rice TW, et al. Enteral omega-3 fatty acid, gamma-linolenic acid, and antioxidant supplementation in acute lung injury. JAMA 2011;306:1574-1581.