The presence and effect of bias in trials of early enteral nutrition in critical care

SummaryBackgroundRandomized trials suggest that early enteral nutrition is beneficial in critically ill adults. However, methodologic bias can overestimate benefit.ObjectiveTo assess the potential effect of methodologic bias on these trials.Study designSystematic review and meta-analysis.Data sourceRandomized trials identified in electronic searches of PUBMED, EMBASE, and the Cochrane Library, and in various handsearches.MethodsThe 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.Data synthesisIn 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.LimitationsSmall numbers of trials and missing information.ConclusionsThe 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.