By Kathryn Radigan, MD
Assistant Professor, Pulmonary Medicine, Northwestern University, Feinberg School of Medicine, Chicago
Dr. Radigan reports no financial relationships relevant to this field of study.
SYNOPSIS: When comparing critically ill patients who receive standard enteral feeding vs permissive underfeeding, there is no difference in 90-day mortality.
SOURCE: Arabi YM, et al. Permissive underfeeding or standard enteral feeding in critically ill adults. N Engl J Med 2015;372:2398-2408.
Arabi et al sought to compare an enteral feeding plan that included permissive underfeeding (restriction of non-protein calories) vs standard enteral feeding in critically ill patients. In this unblinded, randomized, controlled trial conducted at seven tertiary care centers in Saudi Arabia and Canada between November 2009 and September 2014, 894 critically ill patients were randomized to permissive underfeeding (40-60% of calculated caloric requirements) or standard enteral feeding (70-100% caloric requirements) for up to 14 days while maintaining the full recommended amount of protein. The primary outcome was 90-day mortality.
The permissive-underfeeding group received fewer mean calories than did the standard-feeding group (835 ± 297 kcal per day vs 1299 ± 467 kcal per day, P < 0.001; 46% ± 14% vs 71% ± 22% of caloric requirements, P < 0.001) with similar protein intake. For the primary outcome, 121 of the 445 patients (27.2%) in the permissive-underfeeding group and 127 of 440 patients (28.9%) in the standard-feeding group died (relative risk, 0.94; 95% confidence interval, 0.76-1.16; P = 0.58). There were no significant differences between groups with respect to intolerance of feeds, diarrhea, infections, ICU length of stay (LOS), or hospital LOS. The investigators concluded that there was no difference in mortality between patients fed with standard enteral feeding vs permissive underfeeding.
COMMENTARY
Critically ill patients are usually unable to eat by mouth for prolonged periods of time, which can contribute to the poor outcomes associated with critical illness. Multiple studies have explored issues surrounding nutritional support for critically ill patients, comparing trophic vs full enteral feeding, continuous intravenous vs enteral feeding, and timing of feeding. These studies have contributed to our growing, but still limited, knowledge on the ideal nutritional strategy in the ICU. Arabi et al were able to show there was no difference in outcomes for patients who were fed with standard enteral feeding vs permissive underfeeding. These results are similar to two other randomized, controlled trials that evaluated minimal or trophic feeding in patients with acute lung injury or respiratory failure.1,2 Arabi et al note that their trial was different from the two previously published studies in several ways: 1) the degree of caloric restriction was more moderate, but the duration was more prolonged, 2) supplemental protein was given to the permissive-underfeeding group, 3) enteral fluids were administered to minimize differences in enteral feeding, and 4) calories were estimated as total calories (not non-protein calories). Although the researchers hypothesized that a permissive-underfeeding strategy that restricts non-protein calories but preserves protein intake may provide benefit, the evidence suggests there is no difference in outcomes.
To confuse the issue further, some studies have shown that underfeeding in the first ICU week may have some beneficial effects.3,4 Interestingly, the trials that suggest no benefit of reaching calorie goals in the first week of ICU stay often include younger patients. This finding serves as a reminder that critically ill patients within any ICU are a heterogeneous group. Rather than a “one prescription for all” approach, the art of medicine must be applied. Furthermore, we may need to address these questions with a different approach. With no data to support the practice, most critically ill patients are fed on a 24-hour continuous protocol. This practice ignores the natural clocks that allow organisms to anticipate cycles of feeding, activity, and rest — the biologic basis for circadian “hunger.” There are animal models to suggest that feedings out of sync with the metabolic clock in muscle may be ineffective or harmful.5 With the intense focus on calories, protein, and other details, it is possible that the effect of timing beyond early (before 48 hours) vs late has been overlooked. Establishing optimal feeding protocols that prevent muscle dysfunction is crucial as we continue to expand our knowledge of nutritional support strategies in the ICU.
REFERENCES
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Rice TW, et al. Randomized trial of initial trophic versus full-energy enteral nutrition in mechanically ventilated patients with acute respiratory failure. Crit Care Med 2011;39:967-974.
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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: The EDEN randomized trial. JAMA 2012;307:795-803.
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Arabi YM, et al. Permissive underfeeding and intensive insulin therapy in critically ill patients: A randomized controlled trial. Am J Clin Nutr 2011;93:569-577.
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Casaer MP, et al. Early versus late parenteral nutrition in critically ill adults. N Engl J Med 2011;365:506-517.
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Peek CB, et al. Circadian clock NAD+ cycle drives mitochondrial oxidative metabolism in mice. Science 2013;342:1243417.
