Evidence map›Paper›PMID 38229072›Full record

Trial reportCritical care (London, England)2024

Association between urea trajectory and protein dose in critically ill adults: a secondary exploratory analysis of the effort protein trial (RE-EFFORT).

Ryan W Haines, John R Prowle, Andrew Day, Danielle E Bear, Daren K Heyland, Zudin Puthucheary

2 registry-linked trialsOpen access · goldAbstract readRandomized Controlled Trial
PubMed Full text at PMC Publisher
In one paragraph

Trial report in Critical care (London, England), 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 2 registered trials, which are not on this map. Cited by 28 papers, 3 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
28citing papers in PubMed, 3 pooled it
12.7field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT03160547 nacompletednot on this map

The Effect of Higher Protein Dosing in Critically Ill Patients: A Multicenter Registry-based Randomized Trial

TypeinterventionalSponsorClinical Evaluation Research Unit at Kingston General HospitalRan2017 to 2021Enrolled1,329ConditionsCritical Illness, MalnutritionArmsUsual Protein/Amino Acid Group, Higher Protein/Amino Acid Group
NCT07631221 recruitingnot on this mapstarted 2025, after this paper: background citation

Effect of Protein Dosage on Persistent Acute Renal Failure in Critically Ill Patients.

TypeobservationalSponsorHospital Italiano de Buenos AiresRan2025 to 2026Enrolled344ConditionsAcute Kidney Failure, Critical Illness, Protein Intake, Nutritional Support
3 · Its place in the literature

Who cites it

28 citing papers in PubMed, 3 syntheses or guidelines pooled it, 41 citations in OpenAlex.

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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

6 authors at 5 institutions in 2 countries.

Ryan W HainesAdult Critical Care Unit, The Royal London Hospital, Barts Health NHS Trust, Whitechapel Road, London, E1 1BB, UK. r.haines@qmul.ac.uk.
John R ProwleAdult Critical Care Unit, The Royal London Hospital, Barts Health NHS Trust, Whitechapel Road, London, E1 1BB, UK.
Andrew DayClinical Evaluation Research Unit, Kingston Health Science Center, Kingston, ON, Canada.
Danielle E BearDepartments of Critical Care and Nutrition and Dietetics, Guy's and St. Thomas' NHS Foundation Trust, London, UK.
Daren K Heyland *Department of Critical Care Medicine, Queen's University, Kingston, ON, Canada.
Zudin Puthucheary *Adult Critical Care Unit, The Royal London Hospital, Barts Health NHS Trust, Whitechapel Road, London, E1 1BB, UK.
Queen Mary University of London · GBBarts Health NHS Trust · GBGuy's and St Thomas' NHS Foundation Trust · GBKingston Health Sciences Centre · CAQueen's University · CA

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundDelivering higher doses of protein to mechanically ventilated critically ill patients did not improve patient outcomes and may have caused harm. Longitudinal urea measurements could provide additional information about the treatment effect of higher protein doses. We hypothesised that higher urea values over time could explain the potential harmful treatment effects of higher doses of protein.

methodsWe conducted a reanalysis of a randomised controlled trial of higher protein doses in critical illness (EFFORT Protein). We applied Bayesian joint models to estimate the strength of association of urea with 30-day survival and understand the treatment effect of higher protein doses.

resultsOf the 1301 patients included in EFFORT Protein, 1277 were included in this analysis. There were 344 deaths at 30 days post-randomisation. By day 6, median urea was 2.1 mmol/L higher in the high protein group (95% CI 1.1-3.2), increasing to 3.0 mmol/L (95% CI 1.3-4.7) by day 12. A twofold rise in urea was associated with an increased risk of death at 30 days (hazard ratio 1.34, 95% credible interval 1.21-1.48), following adjustment of baseline characteristics including age, illness severity, renal replacement therapy, and presence of AKI. This association persisted over the duration of 30-day follow-up and in models adjusting for evolution of organ failure over time.

conclusionsThe increased risk of death in patients randomised to a higher protein dose in the EFFORT Protein trial was estimated to be mediated by increased urea cycle activity, of which serum urea is a biological signature. Serum urea should be taken into consideration when initiating and continuing protein delivery in critically ill patients. CLINICALTRIALS: gov Identifier: NCT03160547 (2017-05-17).

Indexed as

Continuous Renal Replacement TherapyCritical IllnessAdultBayes TheoremHumansRenal Replacement TherapyUreaUreaIntensive careJoint modellingMulti-organ failureProteinUrea

Identifiers

PMID38229072
PMCPMC10792897
OpenAlexW4390910468

What OpenQuestion holds

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LicenceCC BY
Read underepoch 390

Registered trials

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.