Abstract
BackgroundThe optimal protein dose in critical illness is unknown. We aim to conduct a systematic review of randomized controlled trials (RCTs) to compare the effect of higher versus lower protein delivery (with similar energy delivery between groups) on clinical and patient-centered outcomes in critically ill patients.MethodsWe searched MEDLINE, EMBASE, CENTRAL and CINAHL from database inception through April 1, 2021.We included RCTs of (1) adult (age ≥ 18) critically ill patients that (2) compared higher vs lower protein with (3) similar energy intake between groups, and (4) reported clinical and/or patient-centered outcomes. We excluded studies on immunonutrition. Two authors screened and conducted quality assessment independently and in duplicate. Random-effect meta-analyses were conducted to estimate the pooled risk ratio (dichotomized outcomes) or mean difference (continuous outcomes).ResultsNineteen RCTs were included (n = 1731). Sixteen studies used primarily the enteral route to deliver protein. Intervention was started within 72 h of ICU admission in sixteen studies. The intervention lasted between 3 and 28 days. In 11 studies that reported weight-based nutrition delivery, the pooled mean protein and energy received in higher and lower protein groups were 1.31 ± 0.48 vs 0.90 ± 0.30 g/kg and 19.9 ± 6.9 versus 20.1 ± 7.1 kcal/kg, respectively. Higher vs lower protein did not significantly affect overall mortality [risk ratio 0.91, 95% confidence interval (CI) 0.75–1.10, p = 0.34] or other clinical or patient-centered outcomes. In 5 small studies, higher protein significantly attenuated muscle loss (MD −3.44% per week, 95% CI −4.99 to −1.90; p < 0.0001).ConclusionIn critically ill patients, a higher daily protein delivery was not associated with any improvement in clinical or patient-centered outcomes. Larger, and more definitive RCTs are needed to confirm the effect of muscle loss attenuation associated with higher protein delivery.PROSPERO registration number: CRD42021237530
Highlights
Critical illness is associated with significant skeletal muscle wasting [1, 2]
Summary of main findings In this systematic review and meta-analysis of Randomized controlled trial (RCT) that compared higher vs lower protein delivery in critically ill patients, we found that a 0.48 g/kg/day higher protein delivery had no significant effect on overall mortality and other clinical and patient-centered outcomes
We found no differences in mortality outcomes, there were signal towards improvement in other clinical outcomes
Summary
Critical illness is associated with significant skeletal muscle wasting [1, 2]. Survivors of critical illness often have impaired muscle function, which is associated with physical disability and reduced quality of life (QOL) [3].Lee et al Crit Care (2021) 25:260Exogenous administration of protein/amino acids may attenuate protein losses and aid in the recovery of critically ill patients [4, 5]. Previous systematic reviews and meta-analysis evaluating optimal protein dose in critical illness draw different conclusions. The mean protein delivered between groups was 0.67 ± 0.38 g/kg/day versus (vs) 1.02 ± 0.42 g/kg/day They included studies that tested immunonutrition, which may be plagued by an interaction effect [12]. The systematic reviews by Davies and Fetterplace included studies that had significant differences in calories between groups, which may limit interpretation of results as the confounding effect of calories intake cannot be excluded [12, 13]. We aim to conduct a systematic review of randomized controlled trials (RCTs) to compare the effect of higher versus lower protein delivery (with similar energy delivery between groups) on clinical and patient-centered outcomes in critically ill patients
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