Abstract: We included seven RCTs with a total of 345 participants. Outcome data were limited, and we judged many trials to have an unclear risk of bias in several domains. Early versus delayed enteral nutrition Six trials (318 participants) assessed early versus delayed enteral nutrition in general, medical, and trauma ICUs in the USA, Australia, Greece, India, and Russia. Primary outcomes Five studies (259 participants) measured mortality. It is uncertain whether early enteral nutrition affects the risk of mortality within 30 days (RR 1.00, 95% CI 0.16 to 6.38; 1 study, 38 participants; very low-quality evidence). Four studies (221 participants) reported mortality without describing the timeframe; we did not pool these results. None of the studies reported a clear difference in mortality between groups. Three studies (156 participants) reported infectious complications. We were unable to pool the results due to unreported data and substantial clinical heterogeneity. The results were inconsistent across studies. One trial measured feed intolerance or gastrointestinal complications; it is uncertain whether early enteral nutrition affects this outcome (RR 0.84, 95% CI 0.35 to 2.01; 59 participants; very low-quality evidence). Secondary outcomes One trial assessed hospital length of stay and reported a longer stay in the early enteral group (median 15 days (interquartile range (IQR) 9.5 to 20) versus 12 days (IQR 7.5 to15); P = 0.05; 59 participants; very low-quality evidence). Three studies (125 participants) reported the duration of mechanical ventilation. We did not pool the results due to clinical and statistical heterogeneity. The results were inconsistent across studies. It is uncertain whether early enteral nutrition affects the risk of pneumonia (RR 0.77, 95% CI 0.55 to 1.06; 4 studies, 192 participants; very low-quality evidence). Early enteral nutrition with supplemental parenteral nutrition versus delayed enteral nutrition with supplemental parenteral nutrition We identified one trial in a burn ICU in the USA (27 participants). Primary outcomes It is uncertain whether early enteral nutrition with supplemental parenteral nutrition affects the risk of mortality (RR 0.74, 95% CI 0.25 to 2.18; very low-quality evidence), or infectious complications (MD 0.00, 95% CI -1.94 to 1.94; very low-quality evidence). There were no data available for feed intolerance or gastrointestinal complications. Secondary outcomes It is uncertain whether early enteral nutrition with supplemental parenteral nutrition reduces the duration of mechanical ventilation (MD 9.00, 95% CI -10.99 to 28.99; very low-quality evidence). There were no data available for hospital length of stay or pneumonia. Due to very low-quality evidence, we are uncertain whether early enteral nutrition, compared with delayed enteral nutrition, affects the risk of mortality within 30 days, feed intolerance or gastrointestinal complications, or pneumonia. Due to very low-quality evidence, we are uncertain if early enteral nutrition with supplemental parenteral nutrition compared with delayed enteral nutrition with supplemental parenteral nutrition reduces mortality, infectious complications, or duration of mechanical ventilation. There is currently insufficient evidence; there is a need for large, multicentred studies with rigorous methodology, which measure important clinical outcomes.

Plain-language summary: We searched the literature until April 2019 for RCTs that compared early enteral nutrition with delayed enteral nutrition, with or without SPN, in adults in an ICU. RCTs, if designed and conducted properly, represent the highest methodological standard in clinical research. We included seven RCTs with 345 participants. Participants were admitted to the ICU for more than 72 hours with medical, surgical, or trauma diagnoses. Six trials with 318 participants compared early enteral nutrition with delayed enteral nutrition. One trial with 27 participants compared early enteral nutrition with SPN versus delayed enteral nutrition with SPN. Overall, results showed no clear differences in the number of deaths within 30 days (one study, 38 participants), intolerance to feeding (one study, 59 participants), or development of pneumonia (four studies, 192 participants), between those who received early enteral nutrition or delayed enteral nutrition. We assessed the evidence as very low-quality, meaning the findings could potentially change with additional studies. In the one small trial that also gave SPN, the number of deaths, people with infectious complications, and the duration of mechanical ventilation were not clearly different between those who received early enteral nutrition or delayed enteral nutrition (very low-quality evidence). Future trials should continue to look into the impact of early enteral nutrition, with or without SPN, on important clinical outcomes in adults hospitalized in ICUs. We assessed the quality of the evidence as very low, meaning we were uncertain about the findings, as included studies were small, and provided an unclear description of the methods that they used. Participants in the studies had different causes for their critical illness. The outcomes were not always measured in the same way or at the same time in the different trials; some trials did not report on them.