129 PROTEIN PROVISION AND EXERCISE THERAPY TO IMPROVE OUTCOMES IN ICU-SURVIVORS 7 Exogenous calories, both nutritional (enteral, parenteral) and non-nutritional (e.g. propofol, citrate and intravenous glucose) can hinder increasing protein delivery. Endogenous energy production can add up to 500-1400kcal per day39 and current recommendations are to provide exogenous calories progressively to improve survival.5,39,74,75 Also, it is important to acknowledge that energy/ kcal delivery is a potential confounder in the relationship between protein delivery and outcomes. Several other obstacles influence sufficient nutritional support, for example, dysphagia after extubation,76,77 reduced appetite, delayed gastric emptying, impaired gut motility, early satiety, nausea, vomiting, and diet prescriptions.69,76–81 These examples may be the reason why all included NRSI compared higher protein target with a target below the minimum recommendation of 1.2g/kg/day, since these studies took place in the early phase of critical illness. The number of high-quality studies was limited: the risk of bias was high or serious in more than half of the included studies. Issues regarding blinding of the intervention and missing outcome data were a concern. It is well known that retrospective studies, which were included in this review, are prone to bias since it is not possible to control for all relevant confounders. It makes the establishment of causal relations in these studies questionable. For example, Jeong et al48 presented a statistically significant effect of protein provision on 28-day mortality in patients at risk for malnutrition. This was consistent with other retrospective studies, that showed an association between protein Intervention Comparator n Mean SD n Mean SD MD CI 35 9.0 7 26 7.7 4.7 1.3 [-1.9;4.5] 35 56.3 74.4 26 60 74.5 -3.7 [-34.8; 42.3] 35 11.7 8.3 26 16.3 6.1 -4.6 [-0.74; -8.46]
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