The clinical potential of GDF15 as a "ready-to-feed indicator" for critically ill adults.
Adult
Analysis of Variance
Biomarkers
/ analysis
Critical Illness
/ epidemiology
Female
Growth Differentiation Factor 15
/ analysis
Humans
Length of Stay
/ statistics & numerical data
Linear Models
Male
Middle Aged
Predictive Value of Tests
Prospective Studies
Severity of Illness Index
Statistics, Nonparametric
Time Factors
Critical illness
Feeding intolerance
GDF15
Outcome
Parenteral nutrition
Journal
Critical care (London, England)
ISSN: 1466-609X
Titre abrégé: Crit Care
Pays: England
ID NLM: 9801902
Informations de publication
Date de publication:
14 09 2020
14 09 2020
Historique:
received:
29
06
2020
accepted:
17
08
2020
entrez:
15
9
2020
pubmed:
16
9
2020
medline:
26
5
2021
Statut:
epublish
Résumé
Circulating growth-differentiation factor-15 (GDF15), a cellular stress marker, abruptly increases during critical illness, but its later time course remains unclear. GDF15 physiologically controls oral intake by driving aversive responses to nutrition. Early parenteral nutrition (PN) in ICU patients has overall been shown not beneficial. We hypothesized that low GDF15 can identify patients who benefit from early PN, tolerate enteral nutrition (EN), and resume spontaneous oral intake. In secondary analyses of the EPaNIC-RCT on timing of PN initiation (early PN versus late PN) and the prospective observational DAS study, we documented the time course of circulating GDF15 in ICU (N = 1128) and 1 week post-ICU (N = 72), compared with healthy subjects (N = 65), and the impact hereon of randomization to early PN versus late PN in propensity score-matched groups (N = 564/group). Interaction between upon-admission GDF15 and randomization for its outcome effects was investigated (N = 4393). Finally, association between GDF15 and EN tolerance in ICU (N = 1383) and oral intake beyond ICU discharge (N = 72) was studied. GDF15 was elevated throughout ICU stay, similarly in early PN and late PN patients, and remained high beyond ICU discharge (p < 0.0001). Upon-admission GDF15 did not interact with randomization to early PN versus late PN for its outcome effects, but higher GDF15 independently related to worse outcomes (p ≤ 0.002). Lower GDF15 was only weakly related to gastrointestinal tolerance (p < 0.0001) and a steeper drop in GDF15 with more oral intake after ICU discharge (p = 0.05). In critically ill patients, high GDF15 reflected poor prognosis and may contribute to aversive responses to nutrition. However, the potential of GDF15 as "ready-to-feed indicator" appears limited. ClinicalTrials.gov , NCT00512122, registered 31 July 2007, https://www.clinicaltrials.gov/ct2/show/NCT00512122 (EPaNIC trial) and ISRCTN, ISRCTN 98806770, registered 11 November 2014, http://www.isrctn.com/ISRCTN98806770 (DAS trial).
Sections du résumé
BACKGROUND
Circulating growth-differentiation factor-15 (GDF15), a cellular stress marker, abruptly increases during critical illness, but its later time course remains unclear. GDF15 physiologically controls oral intake by driving aversive responses to nutrition. Early parenteral nutrition (PN) in ICU patients has overall been shown not beneficial. We hypothesized that low GDF15 can identify patients who benefit from early PN, tolerate enteral nutrition (EN), and resume spontaneous oral intake.
METHODS
In secondary analyses of the EPaNIC-RCT on timing of PN initiation (early PN versus late PN) and the prospective observational DAS study, we documented the time course of circulating GDF15 in ICU (N = 1128) and 1 week post-ICU (N = 72), compared with healthy subjects (N = 65), and the impact hereon of randomization to early PN versus late PN in propensity score-matched groups (N = 564/group). Interaction between upon-admission GDF15 and randomization for its outcome effects was investigated (N = 4393). Finally, association between GDF15 and EN tolerance in ICU (N = 1383) and oral intake beyond ICU discharge (N = 72) was studied.
RESULTS
GDF15 was elevated throughout ICU stay, similarly in early PN and late PN patients, and remained high beyond ICU discharge (p < 0.0001). Upon-admission GDF15 did not interact with randomization to early PN versus late PN for its outcome effects, but higher GDF15 independently related to worse outcomes (p ≤ 0.002). Lower GDF15 was only weakly related to gastrointestinal tolerance (p < 0.0001) and a steeper drop in GDF15 with more oral intake after ICU discharge (p = 0.05).
CONCLUSION
In critically ill patients, high GDF15 reflected poor prognosis and may contribute to aversive responses to nutrition. However, the potential of GDF15 as "ready-to-feed indicator" appears limited.
TRIAL REGISTRATION
ClinicalTrials.gov , NCT00512122, registered 31 July 2007, https://www.clinicaltrials.gov/ct2/show/NCT00512122 (EPaNIC trial) and ISRCTN, ISRCTN 98806770, registered 11 November 2014, http://www.isrctn.com/ISRCTN98806770 (DAS trial).
Identifiants
pubmed: 32928255
doi: 10.1186/s13054-020-03254-1
pii: 10.1186/s13054-020-03254-1
pmc: PMC7488998
doi:
Substances chimiques
Biomarkers
0
GDF15 protein, human
0
Growth Differentiation Factor 15
0
Banques de données
ClinicalTrials.gov
['NCT00512122']
ISRCTN
['ISRCTN 98806770']
Types de publication
Journal Article
Observational Study
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
557Subventions
Organisme : Research Foundation-Flanders (FWO)
ID : 1151018N
Pays : International
Organisme : Research Foundation-Flanders (FWO)
ID : 11W9317N
Pays : International
Organisme : Research Foundation-Flanders (FWO)
ID : 1832817N
Pays : International
Organisme : Methusalem program of the Flemish government
ID : METH14/06
Pays : International
Organisme : Methusalem program of the Flemish government
ID : METH14/06
Pays : International
Organisme : FP7 Ideas: European Research Council ()
ID : AdvG-2012-321670
Pays : International
Organisme : H2020 European Research Council
ID : 2017-785809
Pays : International
Organisme : Universitaire Ziekenhuizen Leuven, KU Leuven
ID : Postdoctoral research fellowship
Pays : International
Organisme : KU Leuven
ID : C24/17/070
Pays : International
Organisme : KU Leuven
ID : 24/17/070
Pays : International
Organisme : KU Leuven
ID : STG-16-00253
Pays : International
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