Elsevier

Clinical Nutrition

Volume 37, Issue 6, Part A, December 2018, Pages 1913-1925
Clinical Nutrition

Meta-analyses
Delivery of full predicted energy from nutrition and the effect on mortality in critically ill adults: A systematic review and meta-analysis of randomised controlled trials

https://doi.org/10.1016/j.clnu.2017.09.026Get rights and content

Summary

Background

The amount of energy required to improve clinical outcomes in critically ill adults is unknown.

Objective

The aim of this systematic review and meta-analysis was to evaluate the impact of near target energy delivery to critically ill adults on mortality and other clinically relevant outcomes.

Design

Following PRISMA guidelines, MEDLINE, EMBASE, CINHAL and the Cochrane Library were searched for randomised controlled trials evaluating nutrition interventions in adult critical care populations. Included studies compared delivery of ≥80% of predicted energy requirements (near target) from enteral and/or parenteral nutrition to <80% (standard care) and reported mortality. The quality of individual studies was assessed using the Cochrane ‘Risk of Bias’ tool, and the overall body of evidence using the GRADE approach. Fixed or random effect meta-analyses were used pending the presence of heterogeneity (I2 > 50%) when 3 or more studies reported the same outcome. Outcomes are presented as risk ratio (RR), 95% confidence interval (CI).

Results

Ten trials with 3155 participants were included. Mortality was unaffected by the intervention (RR 1.02, 95% CI 0.81, 1.27, p = 0.89, I2 = 25%). Evaluation of studies of higher quality and low risk of bias did not alter the mortality inference (3 trials, 352 participants, RR 0.83, 95% CI 0.49, 1.40, p = 0.19, I2 = 39%). The quality of evidence across outcomes was very low.

Conclusions

The delivery of near target energy when compared to standard care in adult critically ill patients was not associated with an effect on mortality. Because the quality of the evidence across outcomes was very low there is considerable uncertainty surrounding this estimate. This has implications for clinical utility of the evidence within the included reviews.

Introduction

Nutrition therapy is a widely provided intervention to critically ill patients internationally but there is uncertainty as to the amount of energy that should be provided to optimise outcomes. Several randomised controlled trials (RCTs) have compared the delivery of less than predicted energy requirements in both arms (60–70%) or to even lesser amounts (20–30%) [2], [3], [4]. It can be argued that failing to compare delivery of energy close to targeted requirements risks flawed interpretation and does not reflect current best practice recommendations [5], [6], [7], [8].

The results of the aforementioned trials have been mixed and confusing for clinicians. Methodologies such as systematic reviews and meta-analyses have been utilised to try and combine trial results and obtain guidance. Five published meta-analyses have investigated the role of energy delivery at varying amounts to critically ill adults and the association with clinical outcomes [9], [10], [11], [12], [13]. None have however specifically focused on studies which aim to deliver near target energy levels recommended in best practice guidelines, or completed a quality assessment across outcomes, significantly limiting confidence and clinical utility of the findings [14].

The aim of this systematic review and meta-analysis was to assess the effect of near target energy provision from nutrition (defined as provision of ≥80% of the predicted energy determined by any method) on mortality and other important clinical outcomes in critically ill adults including detailed assessments of evidence quality.

Section snippets

Methods

Methodologies detailed by expert groups and best practice guidelines were utilised in this review [15], [16], [17].

The question posed was “In critically ill adults (population), does delivery of full predicted energy from nutrition (intervention) influence mortality or other important clinical outcomes (outcome) compared to delivery of less than full predicted energy from nutrition (comparator)?” Full details can be viewed on PROSPERO (CRD42015027512) or in the pre-published protocol [1]. In

Results

There were 9335 papers identified and after duplicates and irrelevant papers were excluded on abstracts alone, 509 underwent full text review. Ten papers were eligible including 3155 participants (Fig. 1) [3], [21], [22], [23], [24], [25], [26], [27], [28], [29].

The included trials were conducted in a variety of locations and over a wide range of years (4 in Europe, 2 in the United Kingdom and 1 each in Israel, Australia, Asia and the United States of America between 1997 and 2015). Six studies

Key findings

This systematic review and meta-analysis did not find any associations with delivery of energy at near target (≥80% of predicted amounts), compared to standard care (<80% of predicted amounts) and important clinical outcomes in critically ill adults. However, the quality of evidence for all primary and secondary outcomes was rated ‘very low’ using the GRADE assessment, indicating low confidence in this result. The novelty of this systematic review and meta-analysis is that randomised trials

Conclusions

The delivery of near target energy at ≥ 80% of predicted requirements, when compared to standard care energy delivery, did not influence mortality or any other relevant clinical outcomes in adult critically ill patients. However, the quality of most randomised trials was low, suggesting that the true estimate of effect may be different. Robust large prospective RCTs with consistent reporting are required to determine the optimal amount of energy provision in critical illness, and to provide

Author contribution to the manuscript

EJR and ARD had responsibility for the research design, performed the literature review, collected and analysed the data. EJR, ARD, CH, AD, MB and DJC provided crucial intellectual input to the analysis and interpretation of the results and drafting of the manuscript. All authors read and approved the final manuscript.

Conflict of interest

The authors have no relevant financial or personal disclosures in relation to this work.

Funding

This review was conducted as part of a PhD with funding from the National Health and Medical Research Council (APP1075288).

Disclaimer

ARD, AD and EJR are involved in the TARGET study which investigates the role of energy delivery in critically ill adults (NCT02306746).

Acknowledgements

Thank you to Lorena Romero, Senior Medical Librarian, The Ian Potter Library, Alfred Health for advice during the review.

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