title: The presence and effect of bias in trials of early enteral nutrition in critical care.
abstract: BACKGROUND
  Randomized trials suggest that early enteral nutrition is beneficial in critically ill adults. However, methodologic bias can overestimate benefit.
  
  
  OBJECTIVE
  To assess the potential effect of methodologic bias on these trials.
  
  
  METHODS
  Systematic review and meta-analysis.
  
  
  METHODS
  Randomized trials identified in electronic searches of PUBMED, EMBASE, and the Cochrane Library, and in various handsearches.
  
  
  METHODS
  The primary (mortality, morbidity) and secondary (time on ventilator or in intensive care unit/hospital, cost) outcomes were abstracted from each identified trial comparing early enteral nutrition to no/delayed enteral nutrition. Each trial was assessed for six domains of methodologic bias (sequence generation, allocation concealment, blinding, intention-to-treat, selective outcome reporting, other). No low risk of bias trial (adequate in all six domains) was identified, so such trials could not be compared to the others. Instead, meta-analyses of trials with more or fewer risks were compared in the following ways: adequate methodology to deal with ≥3 or ≤2 domains; Jadad scores ≥3 or ≤2; adequate versus not adequate for each domain.
  
  
  RESULTS
  In the 15 identified trials, early enteral nutrition appeared to improve mortality and infectious morbidity. Mortality benefit was observed only in trials with more risks of bias; infectious morbidity benefit was observed in some analyses of trials with fewer bias risks.
  
  
  CONCLUSIONS
  Small numbers of trials and missing information.
  
  
  CONCLUSIONS
  The benefits attributed to early enteral nutrition were either seen only in trials with high risks of bias or may result from residual risks of bias.
authors.affiliation: Department of Medicine, Olive View-UCLA Medical Center, Sylmar, CA, USA. Electronic address: rkoretz@msn.com.
authors.forename: Ronald L
authors.initials: RL
authors.lastname: Koretz
authors.affiliation: Gastroenterology, Hepatology, and Nutrition Section, Veterans Affairs Medical Center, Washington, D.C., USA. Electronic address: Timothy.Lipman@va.gov.
authors.forename: Timothy O
authors.initials: TO
authors.lastname: Lipman
mesh_terms: D015982:Bias; D003422:Critical Care / Q000379:methods*; D016638:Critical Illness / Q000628:therapy; D004750:Enteral Nutrition / Q000379:methods*; D006801:Humans; D007362:Intensive Care Units; D016032:Randomized Controlled Trials as Topic; D012107:Research Design; D016896:Treatment Outcome
keywords: Critical care; Enteral nutrition; Randomized trials; Risk of bias; Systematic review