Elsevier

The Lancet

Volume 393, Issue 10188, 8–14 June 2019, Pages 2312-2321
The Lancet

Articles
Individualised nutritional support in medical inpatients at nutritional risk: a randomised clinical trial

https://doi.org/10.1016/S0140-6736(18)32776-4Get rights and content

Summary

Background

Guidelines recommend the use of nutritional support during hospital stays for medical patients (patients not critically ill and not undergoing surgical procedures) at risk of malnutrition. However, the supporting evidence for this recommendation is insufficient, and there is growing concern about the possible negative effects of nutritional therapy during acute illness on recovery and clinical outcomes. Our aim was thus to test the hypothesis that protocol-guided individualised nutritional support to reach protein and caloric goals reduces the risk of adverse clinical outcomes in medical inpatients at nutritional risk.

Methods

The Effect of early nutritional support on Frailty, Functional Outcomes, and Recovery of malnourished medical inpatients Trial (EFFORT) is a pragmatic, investigator-initiated, open-label, multicentre study. We recruited medical patients at nutritional risk (nutritional risk screening 2002 [NRS 2002] score ≥3 points) and with an expected length of hospital stay of more than 4 days from eight Swiss hospitals. These participants were randomly assigned (1:1) to receive either protocol-guided individualised nutritional support to reach protein and caloric goals (intervention group) or standard hospital food (control group). Randomisation was done with variable block sizes and stratification according to study site and severity of malnutrition using an interactive web-response system. In the intervention group, individualised nutritional support goals were defined by specialist dietitians and nutritional support was initiated no later than 48 h after admission. Patients in the control group received no dietary consultation. The composite primary endpoint was any adverse clinical outcome defined as all-cause mortality, admission to intensive care, non-elective hospital readmission, major complications, and decline in functional status at 30 days, and it was measured in all randomised patients who completed the trial. This trial is registered with ClinicalTrials.gov, number NCT02517476.

Findings

5015 patients were screened, and 2088 were recruited and monitored between April 1, 2014, and Feb 28, 2018. 1050 patients were assigned to the intervention group and 1038 to the control group. 60 patients withdrew consent during the course of the trial (35 in the intervention group and 25 in the control group). During the hospital stay, caloric goals were reached in 800 (79%) and protein goals in 770 (76%) of 1015 patients in the intervention group. By 30 days, 232 (23%) patients in the intervention group experienced an adverse clinical outcome, compared with 272 (27%) of 1013 patients in the control group (adjusted odds ratio [OR] 0·79 [95% CI 0·64–0·97], p=0·023). By day 30, 73 [7%] patients had died in the intervention group compared with 100 [10%] patients in the control group (adjusted OR 0·65 [0·47–0·91], p=0·011). There was no difference in the proportion of patients who experienced side-effects from nutritional support between the intervention and the control group (162 [16%] vs 145 [14%], adjusted OR 1·16 [0·90–1·51], p=0·26).

Interpretation

In medical inpatients at nutritional risk, the use of individualised nutritional support during the hospital stay improved important clinical outcomes, including survival, compared with standard hospital food. These findings strongly support the concept of systematically screening medical inpatients on hospital admission regarding nutritional risk, independent of their medical condition, followed by a nutritional assessment and introduction of individualised nutritional support in patients at risk.

Funding

The Swiss National Science Foundation and the Research Council of the Kantonsspital Aarau, Switzerland.

Introduction

Anorexia arises as a physiological response to acute illness and predisposes hospital inpatients to serious caloric and protein deficits.1 In combination with immobilisation and a pronounced inflammatory and endocrine stress response, these nutritional deficits contribute to muscle wasting and progressive deterioration of metabolic and functional status, particularly in medical patients with multiple morbidities.2, 3 More than 30% of medical inpatients are at increased risk of malnutrition, a condition that is strongly associated with increased mortality and morbidity, functional decline, prolonged hospital stays, and increased costs of health care.4, 5, 6

Research in context

Evidence before this study

Current clinical practice guidelines recommend to consider initiating nutritional support during the hospital stay of medical inpatients at risk of malnutrition. However, these recommendations are largely based on physiological rationales and observational studies, rather than interventional research. A systematic review and meta-analysis published in 2016 that focused on randomised trials investigating the effects of nutritional interventions on clinical outcomes in medical inpatients, found only 22 trials with a total of 3736 participants. Trials were mostly small and heterogeneous with overall low study quality. The pooled analysis showed that nutritional interventions increased caloric and protein intake, as well as patient weight, but there was no effect on mortality, functional outcomes, or length of hospital stay. Thus, based on current clinical trials, it is still unclear whether systematic screening for malnutrition in medical patients on their admission to hospital and introduction of nutritional support in patients at risk has positive effects on clinical outcomes.

Added value of this study

This pragmatic, large-scale, multicentre trial showed that early use of individualised nutritional support to reach protein and caloric goals in medical inpatients at nutritional risk is effective in increasing caloric and protein intakes and in lowering the risk of adverse outcomes and mortality within 30 days. Patients receiving nutritional support also had improvements in functional outcomes and quality of life. The beneficial effects of nutritional support were robust and comparable in subgroups according to patient age, sex, severity of nutritional risk, and underlying disease.

Implications of all the available evidence

Malnutrition is a highly prevalent condition in medical inpatients that negatively impacts clinical outcomes. In conjunction with results of earlier smaller trials and observational research, findings of EFFORT strongly support the concept of systematically screening medical inpatients on their admission to hospital regarding nutritional risk, independent of medical condition, followed by a nutritional assessment and introduction of individualised nutritional support in patients at risk.

Current clinical practice guidelines, including those by the European Society for Clinical Nutrition and Metabolism7 and the American Society for Parenteral and Enteral Nutrition,8 recommend considering placing medical inpatients identified by screening and assessment as being at risk of malnutrition on nutritional support during their hospital stay. However, these recommendations are largely based on physiological rationales and observational studies. Some small trials have found that nutritional support reduced the length of hospital stays and decreased mortality.9, 10, 11, 12 Yet, two meta-analyses reported no significant improvements in clinical outcomes associated with nutritional interventions in medical inpatients receiving nutritional support, despite their increased caloric and protein intake.13, 14 Additionally, the introduction of nutritional support in medical inpatients with acute illnesses is currently challenged by results of several high-quality trials in critical care settings, which reported harmful effects of full replacement nutrition strategies.1 These negative effects might be explained by suppression of autophagy with inadequate clearance of acute cell damage associated with illness.15

In view of the scarcity of high-quality data from medical inpatients and possible conflicts between current recommendations for medical inpatients and trials of critical care, we did the Effect of early nutritional support on Frailty, Functional Outcomes, and Recovery of malnourished medical inpatients Trial (EFFORT). We tested the hypothesis that protocol-guided individualised nutritional support to reach protein and caloric goals reduces the risk of adverse clinical outcomes in medical inpatients at nutritional risk.

Section snippets

Study design and participants

EFFORT is a pragmatic, investigator-initiated, open-label, non-blinded, non-commercial, multicentre, randomised, controlled trial, that was undertaken in eight Swiss hospitals. The rationale for the trial, design details, and eligibility features have been published previously.16

The eight participating sites were secondary and tertiary care hospitals and included the University Clinic in Aarau, the University Hospital in Bern, the Cantonal hospitals in Lucerne, Solothurn, St Gallen,

Results

From April 1, 2014, to Feb 28, 2018, we screened 5015 patients and enrolled 2088. Of these, 1050 were randomly assigned to the intervention group and 1038 to the control group. With 60 patients withdrawing consent and no other participants lost to follow-up, our final evaluable cohort consisted of 2028 patients (1015 patients in the intervention group and 1013 patients in the control group; figure 2).

Baseline characteristics were similar between groups (table 1, appendix). Patients had a mean

Discussion

In this multicentre trial, compared with a control group receiving standard hospital food, individualised nutritional support increased daily energy and protein intakes and lowered the risk of adverse clinical outcomes at 30 days (primary outcome) and all-cause mortality with improvements in functional status and quality of life without an apparent increase in adverse events from the intervention.

Several points of this trial are worth mentioning. First, our findings validate some previous

Data sharing

We intend to make data collected for the study, including anonymised individual participant data and a data dictionary defining each field in the set, available to others. Related documents will be available, including the trial protocol and the statistical analysis plan. These data will be available with the publication of our main manuscript and all secondary projects as outlined in our trial protocol on receipt of a letter of intention detailing the study hypothesis and statistical analysis

References (32)

  • N Friedli et al.

    Management and prevention of refeeding syndrome in medical inpatients: an evidence-based and consensus-supported algorithm

    Nutrition

    (2018)
  • MP Casaer et al.

    Nutrition in the acute phase of critical illness

    N Engl J Med

    (2014)
  • P Schutz et al.

    Loss of appetite in acutely ill medical inpatients: physiological response or therapeutic target?

    Swiss Med Wkly

    (2014)
  • S Felder et al.

    Unraveling the link between malnutrition and adverse clinical outcomes: association of acute and chronic malnutrition measures with blood biomarkers from different pathophysiological states

    Ann Nutr Metab

    (2016)
  • C Mueller et al.

    ASPEN clinical guidelines: nutrition screening, assessment, and intervention in adults

    JPEN J Parenter Enteral Nutr

    (2011)
  • JM Potter et al.

    Protein energy supplements in unwell elderly patients—a randomized controlled trial

    JPEN J Parenter Enteral Nutr

    (2001)
  • Cited by (511)

    View all citing articles on Scopus

    Equally contributing senior authors

    View full text