Permissive Underfeeding or Standard Enteral Feeding in Critically Ill Adults.

BACKGROUND The appropriate caloric goal for critically ill adults is unclear. We evaluated the effect of restriction of nonprotein calories (permissive underfeeding), as compared with standard enteral feeding, on 90-day mortality among critically ill adults, with maintenance of the full recommended amount of protein in both groups. METHODS At seven centers, we randomly assigned 894 critically ill adults with a medical, surgical, or trauma admission category to permissive underfeeding (40 to 60% of calculated caloric requirements) or standard enteral feeding (70 to 100%) for up to 14 days while maintaining a similar protein intake in the two groups. The primary outcome was 90-day mortality. RESULTS Baseline characteristics were similar in the two groups; 96.8% of the patients were receiving mechanical ventilation. During the intervention period, the permissive-underfeeding group received fewer mean (±SD) 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). Protein intake was similar in the two groups (57±24 g per day and 59±25 g per day, respectively; P=0.29). The 90-day mortality was similar: 121 of 445 patients (27.2%) in the permissive-underfeeding group and 127 of 440 patients (28.9%) in the standard-feeding group died (relative risk with permissive underfeeding, 0.94; 95% confidence interval [CI], 0.76 to 1.16; P=0.58). No serious adverse events were reported; there were no significant between-group differences with respect to feeding intolerance, diarrhea, infections acquired in the intensive care unit (ICU), or ICU or hospital length of stay. CONCLUSIONS Enteral feeding to deliver a moderate amount of nonprotein calories to critically ill adults was not associated with lower mortality than that associated with planned delivery of a full amount of nonprotein calories. (Funded by the King Abdullah International Medical Research Center; PermiT Current Controlled Trials number, ISRCTN68144998.).

[1]  R. Wolfe,et al.  Proteins and amino acids are fundamental to optimal nutrition support in critically ill patients , 2014, Critical Care.

[2]  G. Stukenborg,et al.  Hypocaloric compared with eucaloric nutritional support and its effect on infection rates in a surgical intensive care unit: a randomized controlled trial. , 2014, The American journal of clinical nutrition.

[3]  C. Pichard,et al.  Pragmatic approach to nutrition in the ICU: expert opinion regarding which calorie protein target. , 2014, Clinical nutrition.

[4]  R. Weindruch,et al.  Caloric restriction reduces age-related and all-cause mortality in rhesus monkeys , 2014, Nature Communications.

[5]  S. Finfer,et al.  Early Parenteral Nutrition in Critically Ill Patients With Short-term Relative Contraindications to Early Enteral Nutrition: A Randomized Controlled Trial , 2014 .

[6]  Li Zhang,et al.  Beneficial Effects of Short-Term Calorie Restriction against Cisplatin-Induced Acute Renal Injury in Aged Rats , 2014, Nephron Experimental Nephrology.

[7]  J. Levijoki,et al.  Caloric restriction ameliorates kidney ischaemia/reperfusion injury through PGC‐1α–eNOS pathway and enhanced autophagy , 2013, Acta physiologica.

[8]  S. Mehta,et al.  Permissive underfeeding versus target enteral feeding in adult critically ill patients (PermiT Trial): a study protocol of a multicenter randomized controlled trial , 2012, Trials.

[9]  T. Rice,et al.  Initial Trophic vs Full Enteral Feeding in Patients With Acute Lung Injury: The EDEN Randomized Trial , 2012 .

[10]  A. Day,et al.  Optimal amount of calories for critically ill patients: Depends on how you slice the cake!* , 2011, Critical care medicine.

[11]  G. Van den Berghe,et al.  Early versus Late Parenteral Nutrition in Critically Ill Adults , 2011, The New England journal of medicine.

[12]  G. Bernard,et al.  Randomized trial of initial trophic versus full-energy enteral nutrition in mechanically ventilated patients with acute respiratory failure , 2011, Critical care medicine.

[13]  Y. Arabi,et al.  Permissive underfeeding and intensive insulin therapy in critically ill patients: a randomized controlled trial. , 2011, The American journal of clinical nutrition.

[14]  P. Singer,et al.  The tight calorie control study (TICACOS): a prospective, randomized, controlled pilot study of nutritional support in critically ill patients , 2011, Intensive Care Medicine.

[15]  Y. Arabi,et al.  Near-target caloric intake in critically ill medical-surgical patients is associated with adverse outcomes. , 2010, JPEN. Journal of parenteral and enteral nutrition.

[16]  W. V. van IJcken,et al.  Short‐term dietary restriction and fasting precondition against ischemia reperfusion injury in mice , 2010, Aging cell.

[17]  S. McClave,et al.  Guidelines for the provision and assessment of nutrition support therapy in the adult critically ill patient: Society of Critical Care Medicine and American Society for Parenteral and Enteral Nutrition: Executive Summary* , 2009, Critical care medicine.

[18]  R. Heuberger,et al.  Predictive equations for energy needs for the critically ill. , 2009, Respiratory care.

[19]  A. Delaney,et al.  Effect of evidence-based feeding guidelines on mortality of critically ill adults: a cluster randomized controlled trial. , 2008, JAMA.

[20]  Claude Pichard,et al.  Prognostic impact of disease-related malnutrition. , 2008, Clinical nutrition.

[21]  Megan Boitano Hypocaloric feeding of the critically ill. , 2006, Nutrition in clinical practice : official publication of the American Society for Parenteral and Enteral Nutrition.

[22]  Corby K. Martin,et al.  Effect of 6-month calorie restriction on biomarkers of longevity, metabolic adaptation, and oxidative stress in overweight individuals: a randomized controlled trial. , 2006, JAMA.

[23]  John W Devlin,et al.  Effect of low-calorie parenteral nutrition on the incidence and severity of hyperglycemia in surgical patients: A randomized, controlled trial , 2005, Critical care medicine.

[24]  Myriam Gorospe,et al.  Calorie Restriction Promotes Mammalian Cell Survival by Inducing the SIRT1 Deacetylase , 2004, Science.

[25]  D. Frankenfield,et al.  Validation of 2 approaches to predicting resting metabolic rate in critically ill patients. , 2004, JPEN. Journal of parenteral and enteral nutrition.

[26]  Lewis Rubinson,et al.  Low caloric intake is associated with nosocomial bloodstream infections in patients in the medical intensive care unit* , 2004, Critical care medicine.

[27]  W. Sibbald,et al.  Multicentre, cluster-randomized clinical trial of algorithms for critical-care enteral and parenteral therapy (ACCEPT). , 2004, CMAJ : Canadian Medical Association journal = journal de l'Association medicale canadienne.

[28]  E. Ravussin,et al.  Calorie restriction and aging: review of the literature and implications for studies in humans. , 2003, The American journal of clinical nutrition.

[29]  G. Fink,et al.  Calorie restriction extends Saccharomyces cerevisiae lifespan by increasing respiration , 2002, Nature.

[30]  R. Dickerson,et al.  Hypocaloric enteral tube feeding in critically ill obese patients. , 2002, Nutrition.

[31]  K. Jeejeebhoy,et al.  Effect of hypoenergetic feeding and refeeding on muscle and mononuclear cell activities of mitochondrial complexes I--IV in enterally fed rats. , 2001, The American journal of clinical nutrition.

[32]  R. A. Forse,et al.  Hypocaloric total parenteral nutrition: Effectiveness in prevention of hyperglycemia and infectious complications—A randomized clinical trial , 2000, Critical care medicine.

[33]  R. Nelson,et al.  Prospective, randomized, controlled trial to determine the effect of early enhanced enteral nutrition on clinical outcome in mechanically ventilated patients suffering head injury. , 1999, Critical care medicine.

[34]  C. Sprung,et al.  Use of the SOFA score to assess the incidence of organ dysfunction/failure in intensive care units: results of a multicenter, prospective study. Working group on "sepsis-related problems" of the European Society of Intensive Care Medicine. , 1998, Critical care medicine.

[35]  C. Baxter,et al.  Equations for the estimation of energy expenditures in patients with burns with special reference to ventilatory status. , 1992, The Journal of burn care & rehabilitation.

[36]  E. Draper,et al.  APACHE II: A severity of disease classification system , 1985, Critical care medicine.

[37]  G. Diette,et al.  Caloric Intake in Medical ICU Patients: Consistency of Care With Guidelines and Relationship to Clinical Outcomes. , 2004, Nutrition in clinical practice : official publication of the American Society for Parenteral and Enteral Nutrition.

[38]  B. Bistrian,et al.  Intensive insulin therapy in critically ill patients. , 2002, The New England journal of medicine.

[39]  J. Klein Nonprotein vs total calories--what are most clinicians using? , 1996, Nutrition in clinical practice : official publication of the American Society for Parenteral and Enteral Nutrition.