Protein and energy delivery in critically ill adult patients and the impact on nutritional and patient-centred outcomes

© 2020 Kate Emily FetterplaceAdult patients who survive critical illness are known to be at risk of several adverse health consequences, including substantial muscle loss, impaired muscle function and reduced quality of life. While nutrition interventions for critically ill patients may attenuate muscle loss, this therapeutic approach remains unproven. Evidence published by others over the period of this PhD program challenged the existing orthodoxy that greater overall calorie provision during the acute phase of critical illness improves overall patient outcomes. Accordingly, the PhD candidate specifically investigated the relationship between protein provision in critical illness and patient-centred outcomes. This thesis comprises several discrete but aligned studies, including a systematic and narrative review of the literature, three observational studies, and a pilot parallel group randomised clinical trial (RCT). The systematic review and meta-analysis established that current practice guidelines recommending the amount of enteral protein are not based on strong evidence. Moreover, there is a lack of high-quality data about the impact of protein provision on functional outcomes that are important to patients. The narrative review evaluated the methodologies and outcomes used to quantify the effect of nutrition therapy in the critically ill. While patient centred and less direct surrogate clinical outcomes are increasingly being used in the nutrition literature, there remains substantial variation in the tools used and the outcomes selected. In a prospective observational study of patients surviving an intensive care unit (ICU) admission following serious trauma, it was identified that many of the outcomes that would be desirable to measure were not feasible after ICU discharge in this patient cohort. In contrast, it was feasible to implement these methodologies in ICU in a separate cohort of critically ill patients, and cumulative nutrition deficits in the latter study were associated with inferior nutritional and patient-centred outcomes, including the presence of malnutrition and ICU-acquired weakness and greater loss of fat-free mass. To evaluate whether it was feasible to increase the enteral protein received by at-risk ICU patients to the doses recommended in practice guidelines, and establish point estimates for the impact of this strategy on patient-centred outcomes, a parallel group RCT was conducted. This single-centre single-blinded pilot trial compared an intervention of a ‘volume-based’ enteral feeding protocol with protein supplementation to usual care. The intervention delivered greater amounts of protein and energy than received by the usual care group, and this was associated with attenuation of muscle loss and reduced prevalence of malnutrition in survivors at ICU discharge. These data are novel, describing the first successful delivery of enteral protein within current guideline recommendations and a consequent favourable effect on muscle mass. Based on this program of work, a multi-centre randomised clinical trial is required to explore the signals observed in these studies, and to generate robust evidence regarding optimal provision of enteral protein during critical illness and the impacts on functional recovery and quality of life in those who survive