Timing of (supplemental) parenteral nutrition in critically ill patients: a systematic review

Supplemental parenteral nutrition (SPN) is used in a step-up approach when full enteral support is contraindicated or fails to reach caloric targets. Recent nutrition guidelines present divergent advices regarding timing of SPN in critically ill patients ranging from early SPN (<48 h after admission; EPN) to postponing initiation of SPN until day 8 after Intensive Care Unit (ICU) admission (LPN). This systematic review summarizes results of prospective studies among adult ICU patients addressing the best timing of (supplemental) parenteral nutrition (S)PN. A structured PubMed search was conducted to identify eligible articles. Articles were screened and selected using predetermined criteria and appraised for relevance and validity. After critical appraisal, four randomized controlled trials (RCTs) and two prospective observational studies remained. One RCT found a higher percentage of alive discharge from the ICU at day 8 in the LPN group compared to EPN group (p = 0.007) but no differences in ICU and in-hospital mortality. None of the other RCTs found differences in ICU or in-hospital mortality rates. Contradicting or divergent results on other secondary outcomes were found for ICU length of stay, hospital length of stay, infection rates, nutrition targets, duration of mechanical ventilation, glucose control, duration of renal replacement therapy, muscle wasting and fat loss. Although the heterogeneity in quality and design of relevant studies precludes firm conclusions, it is reasonable to assume that in adult critically ill patients, there are no clinically relevant benefits of EPN compared with LPN with respect to morbidity or mortality end points, when full enteral support is contraindicated or fails to reach caloric targets. However, considering that infectious morbidity and resolution of organ failure may be negatively affected through mechanisms not yet clearly understood and acquisition costs of parenteral nutrition are higher, the early administration of parenteral nutrition cannot be recommended.