title: Role of timing and dose of energy received in patients with acute lung injury on mortality in the Intensive Nutrition in Acute Lung Injury Trial (INTACT): a post hoc analysis.
abstract: Our trial INTACT (Intensive Nutrition in Acute Lung Injury Trial) was designed to compare the impact of feeding from acute lung injury (ALI) diagnosis to hospital discharge, an interval that, to our knowledge, has not yet been explored. It was stopped early because participants who were randomly assigned to energy intakes at nationally recommended amounts via intensive medical nutrition therapy experienced significantly higher mortality hazards than did those assigned to standard nutrition support care that provided energy at 55% of recommended concentrations.
  
  
  
  We assessed the influence of dose and timing of feeding on hospital mortality.
  
  
  
  Participants (n = 78) were dichotomized as died or discharged alive. Associations between the energy and protein received overall, early (days 1-7), and late (days ≥8) and the hazards of hospital mortality were evaluated between groups with multivariable analysis methods.
  
  
  
  Higher overall energy intake predicted significantly higher mortality (OR: 1.14, 95% CI: 1.02, 1.27). Among participants enrolled for ≥8 d (n = 66), higher early energy intake significantly increased the HR for mortality (HR: 1.17, 95% CI: 1.07, 1.28), whereas higher late energy intake was significantly protective (HR: 0.91, 95% CI: 0.83, 1.0). Results were similar for early but not late protein (grams per kilogram) exposure (early-exposure HR: 8.9, 95% CI: 2.3, 34.3; late-exposure HR: 0.15, 95% CI: 0.02, 1.1). Threshold analyses indicated early mean intakes ≥18 kcal/kg significantly increased subsequent mortality.
  
  
  
  Providing kilocalories per kilogram or grams of protein per kilogram early post-ALI diagnosis at recommended levels was associated with significantly higher hazards for mortality, whereas higher late energy intakes reduced mortality hazards. This time-varying effect violated the Cox proportionality assumption, indicating that feeding trials in similar populations should extend beyond 7 d and use time-varying statistical methods. Future trials are required for corroboration. INTACT was registered at clinicaltrials.gov as NCT01921101.
authors.affiliation: Department of Kinesiology and Nutrition and braunsch@uic.edu.
authors.forename: Carol L
authors.initials: CL
authors.lastname: Braunschweig
authors.affiliation: Division of Epidemiology and Biostatistics, University of Illinois at Chicago, Chicago, IL.
authors.forename: Sally
authors.initials: S
authors.lastname: Freels
authors.affiliation: Department of Health Promotion, Loyola University Chicago, Chicago, IL; and Departments of.
authors.forename: Patricia M
authors.initials: PM
authors.lastname: Sheean
authors.affiliation: Food and Nutrition and.
authors.forename: Sarah J
authors.initials: SJ
authors.lastname: Peterson
authors.affiliation: Department of Kinesiology and Nutrition and.
authors.forename: Sandra Gomez
authors.initials: SG
authors.lastname: Perez
authors.affiliation: Department of Kinesiology and Nutrition and.
authors.forename: Liam
authors.initials: L
authors.lastname: McKeever
authors.affiliation: Medicine, Rush University Medical Center, Chicago, IL.
authors.forename: Omar
authors.initials: O
authors.lastname: Lateef
authors.affiliation: Medicine, Rush University Medical Center, Chicago, IL.
authors.forename: David
authors.initials: D
authors.lastname: Gurka
authors.affiliation: Department of Kinesiology and Nutrition and.
authors.forename: Giamila
authors.initials: G
authors.lastname: Fantuzzi
mesh_terms: D055371:Acute Lung Injury / Q000401:mortality*; D000328:Adult; D000368:Aged; D018592:Cross-Over Studies; D004044:Dietary Proteins / Q000008:administration & dosage; D002149:Energy Intake; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009752:Nutritional Status; D018529:Nutritional Support; D010351:Patient Discharge; D016016:Proportional Hazards Models
chemical_list: D004044:Dietary Proteins
keywords: acute lung injury; critical care; energy dose and timing; energy requirement; medical nutrition therapy; post hoc secondary analysis; randomized clinical trial; threshold effect