A Patient-Level Meta-Analysis of Intensive Glucose Control in Critically Ill Adults

Derick Adigbli; Yang Li; Naomi Hammond; Richard Chatoor; Anthony G. Devaux; Qiang Li; Laurent Billot; Djillali Annane; Yaseen Arabi; Federico Bilotta; Julien Bohé; Frank Martin Brunkhorst; Alexandre Biasi Cavalcanti; Deborah Cook; Christoph Engel; Deborah Green-LaRoche; Wei He; William Henderson; Cornelia Hoedemaekers; Gaetano Iapichino; Pierre Kalfon; Gisela de La Rosa; Afsaneh Lahooti; Iain Mackenzie; Sajeev Mahendran; Christian Mélot; Imogen Mitchell; Tuomas Oksanen; Federico Polli; Jean-Charles Preiser; Francisco Garcia Soriano; Ruan Vlok; Lingcong Wang; Yuan Xu; Anthony P. Delaney; Gian Luca Di Tanna; Simon Finfer

doi:10.1056/EVIDoa2400082

A Patient-Level Meta-Analysis of Intensive Glucose Control in Critically Ill Adults

Derick Adigbli
, Yang Li
, Naomi Hammond
, Richard Chatoor
, Anthony G. Devaux
, Qiang Li
, Laurent Billot
, Djillali Annane
, Yaseen Arabi
, Federico Bilotta
, Julien Bohé
, Frank Martin Brunkhorst
, Alexandre Biasi Cavalcanti
, Deborah Cook
, Christoph Engel
, Deborah Green-LaRoche
, Wei He
, William Henderson
, Cornelia Hoedemaekers
, Gaetano Iapichino

Pierre Kalfon, Gisela de La Rosa, Afsaneh Lahooti, Iain Mackenzie, Sajeev Mahendran, Christian Mélot, Imogen Mitchell, Tuomas Oksanen, Federico Polli, Jean-Charles Preiser, Francisco Garcia Soriano, Ruan Vlok, Lingcong Wang, Yuan Xu, Anthony P. Delaney, Gian Luca Di Tanna, Simon Finfer

School of Science

The George Institute for Global Health
University of Melbourne
University College London
Austin Health
Royal North Shore Hospital
Hôpital Raymond Poincaré
Université Paris-Saclay
King Saud bin Abdulaziz University for Health Sciences
University of Rome La Sapienza
Hospices civils de Lyon
Jena University Hospital
HCor Research Institute
McMaster University
Leipzig University
Tufts University
Capital Medical University
University of British Columbia
Radboud University Medical Center
Università degli Studi di Milano
La Casamance Private Hospital
Hospital Pablo Tobon Uribe
InterSystems Corporation, Cambridge
University of Sydney
Université libre de Bruxelles
Canberra Health Services Library
Australian National University
Helsinki University Hospital
Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico
Universidade de São Paulo
CareFlight Australia
Zhejiang Chinese Medical University
Tsinghua University
University of Applied Sciences and Arts of Southern Switzerland
University of Bern
University of New South Wales
Imperial College London

Research output: Contribution to journal › Article › peer-review

17 Citations (Scopus)

Abstract

BACKGROUND Whether intensive glucose control reduces mortality in critically ill patients remains uncertain. Patient-level meta-analyses can provide more precise estimates of treatment effects than are currently available. METHODS We pooled individual patient data from randomized trials investigating intensive glucose control in critically ill adults. The primary outcome was in-hospital mortality. Secondary outcomes included survival to 90 days and time to live cessation of treatment with vasopressors or inotropes, mechanical ventilation, and newly commenced renal replacement. Severe hypoglycemia was a safety outcome. RESULTS Of 38 eligible trials (n=29,537 participants), 20 (n=14,171 participants) provided individual patient data including in-hospital mortality status for 7059 and 7049 participants allocated to intensive and conventional glucose control, respectively. Of these 1930 (27.3%) and 1891 (26.8%) individuals assigned to intensive and conventional control, respectively, died (risk ratio, 1.02; 95% confidence interval [CI], 0.96 to 1.07; P=0.52; moderate certainty). There was no apparent heterogeneity of treatment effect on in-hospital mortality in any examined subgroups. Intensive glucose control increased the risk of severe hypoglycemia (risk ratio, 3.38; 95% CI, 2.99 to 3.83; P<0.0001). CONCLUSIONS Intensive glucose control was not associated with reduced mortality risk but increased the risk of severe hypoglycemia. We did not identify a subgroup of patients in whom intensive glucose control was beneficial.

Original language	English
Number of pages	14
Journal	NEJM Evidence
Volume	3
Issue number	8
DOIs	https://doi.org/10.1056/EVIDoa2400082
Publication status	Published - Aug 2024

Bibliographical note

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© 2024 Massachussetts Medical Society. All rights reserved.

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Adigbli, D., Li, Y., Hammond, N., Chatoor, R., Devaux, A. G., Li, Q., Billot, L., Annane, D., Arabi, Y., Bilotta, F., Bohé, J., Brunkhorst, F. M., Cavalcanti, A. B., Cook, D., Engel, C., Green-LaRoche, D., He, W., Henderson, W., Hoedemaekers, C., ... Finfer, S. (2024). A Patient-Level Meta-Analysis of Intensive Glucose Control in Critically Ill Adults. NEJM Evidence, 3(8). https://doi.org/10.1056/EVIDoa2400082

@article{48922be18b25480ab762fb1396395b9d,

title = "A Patient-Level Meta-Analysis of Intensive Glucose Control in Critically Ill Adults",

abstract = "BACKGROUND Whether intensive glucose control reduces mortality in critically ill patients remains uncertain. Patient-level meta-analyses can provide more precise estimates of treatment effects than are currently available. METHODS We pooled individual patient data from randomized trials investigating intensive glucose control in critically ill adults. The primary outcome was in-hospital mortality. Secondary outcomes included survival to 90 days and time to live cessation of treatment with vasopressors or inotropes, mechanical ventilation, and newly commenced renal replacement. Severe hypoglycemia was a safety outcome. RESULTS Of 38 eligible trials (n=29,537 participants), 20 (n=14,171 participants) provided individual patient data including in-hospital mortality status for 7059 and 7049 participants allocated to intensive and conventional glucose control, respectively. Of these 1930 (27.3\%) and 1891 (26.8\%) individuals assigned to intensive and conventional control, respectively, died (risk ratio, 1.02; 95\% confidence interval [CI], 0.96 to 1.07; P=0.52; moderate certainty). There was no apparent heterogeneity of treatment effect on in-hospital mortality in any examined subgroups. Intensive glucose control increased the risk of severe hypoglycemia (risk ratio, 3.38; 95\% CI, 2.99 to 3.83; P<0.0001). CONCLUSIONS Intensive glucose control was not associated with reduced mortality risk but increased the risk of severe hypoglycemia. We did not identify a subgroup of patients in whom intensive glucose control was beneficial.",

author = "Derick Adigbli and Yang Li and Naomi Hammond and Richard Chatoor and Devaux, \{Anthony G.\} and Qiang Li and Laurent Billot and Djillali Annane and Yaseen Arabi and Federico Bilotta and Julien Boh{\'e} and Brunkhorst, \{Frank Martin\} and Cavalcanti, \{Alexandre Biasi\} and Deborah Cook and Christoph Engel and Deborah Green-LaRoche and Wei He and William Henderson and Cornelia Hoedemaekers and Gaetano Iapichino and Pierre Kalfon and Rosa, \{Gisela de La\} and Afsaneh Lahooti and Iain Mackenzie and Sajeev Mahendran and Christian M{\'e}lot and Imogen Mitchell and Tuomas Oksanen and Federico Polli and Jean-Charles Preiser and Soriano, \{Francisco Garcia\} and Ruan Vlok and Lingcong Wang and Yuan Xu and Delaney, \{Anthony P.\} and Tanna, \{Gian Luca Di\} and Simon Finfer",

year = "2024",

month = aug,

doi = "10.1056/EVIDoa2400082",

language = "English",

volume = "3",

journal = "NEJM Evidence",

issn = "2766-5526",

publisher = "Massachussetts Medical Society",

number = "8",

}

Adigbli, D, Li, Y, Hammond, N, Chatoor, R, Devaux, AG, Li, Q, Billot, L, Annane, D, Arabi, Y, Bilotta, F, Bohé, J, Brunkhorst, FM, Cavalcanti, AB, Cook, D, Engel, C, Green-LaRoche, D, He, W, Henderson, W, Hoedemaekers, C, Iapichino, G, Kalfon, P, Rosa, GDL, Lahooti, A, Mackenzie, I, Mahendran, S, Mélot, C, Mitchell, I, Oksanen, T, Polli, F, Preiser, J-C, Soriano, FG, Vlok, R, Wang, L, Xu, Y, Delaney, AP, Tanna, GLD & Finfer, S 2024, 'A Patient-Level Meta-Analysis of Intensive Glucose Control in Critically Ill Adults', NEJM Evidence, vol. 3, no. 8. https://doi.org/10.1056/EVIDoa2400082

TY - JOUR

T1 - A Patient-Level Meta-Analysis of Intensive Glucose Control in Critically Ill Adults

AU - Adigbli, Derick

AU - Li, Yang

AU - Hammond, Naomi

AU - Chatoor, Richard

AU - Devaux, Anthony G.

AU - Li, Qiang

AU - Billot, Laurent

AU - Annane, Djillali

AU - Arabi, Yaseen

AU - Bilotta, Federico

AU - Bohé, Julien

AU - Brunkhorst, Frank Martin

AU - Cavalcanti, Alexandre Biasi

AU - Cook, Deborah

AU - Engel, Christoph

AU - Green-LaRoche, Deborah

AU - He, Wei

AU - Henderson, William

AU - Hoedemaekers, Cornelia

AU - Iapichino, Gaetano

AU - Kalfon, Pierre

AU - Rosa, Gisela de La

AU - Lahooti, Afsaneh

AU - Mackenzie, Iain

AU - Mahendran, Sajeev

AU - Mélot, Christian

AU - Mitchell, Imogen

AU - Oksanen, Tuomas

AU - Polli, Federico

AU - Preiser, Jean-Charles

AU - Soriano, Francisco Garcia

AU - Vlok, Ruan

AU - Wang, Lingcong

AU - Xu, Yuan

AU - Delaney, Anthony P.

AU - Tanna, Gian Luca Di

AU - Finfer, Simon

PY - 2024/8

Y1 - 2024/8

N2 - BACKGROUND Whether intensive glucose control reduces mortality in critically ill patients remains uncertain. Patient-level meta-analyses can provide more precise estimates of treatment effects than are currently available. METHODS We pooled individual patient data from randomized trials investigating intensive glucose control in critically ill adults. The primary outcome was in-hospital mortality. Secondary outcomes included survival to 90 days and time to live cessation of treatment with vasopressors or inotropes, mechanical ventilation, and newly commenced renal replacement. Severe hypoglycemia was a safety outcome. RESULTS Of 38 eligible trials (n=29,537 participants), 20 (n=14,171 participants) provided individual patient data including in-hospital mortality status for 7059 and 7049 participants allocated to intensive and conventional glucose control, respectively. Of these 1930 (27.3%) and 1891 (26.8%) individuals assigned to intensive and conventional control, respectively, died (risk ratio, 1.02; 95% confidence interval [CI], 0.96 to 1.07; P=0.52; moderate certainty). There was no apparent heterogeneity of treatment effect on in-hospital mortality in any examined subgroups. Intensive glucose control increased the risk of severe hypoglycemia (risk ratio, 3.38; 95% CI, 2.99 to 3.83; P<0.0001). CONCLUSIONS Intensive glucose control was not associated with reduced mortality risk but increased the risk of severe hypoglycemia. We did not identify a subgroup of patients in whom intensive glucose control was beneficial.

AB - BACKGROUND Whether intensive glucose control reduces mortality in critically ill patients remains uncertain. Patient-level meta-analyses can provide more precise estimates of treatment effects than are currently available. METHODS We pooled individual patient data from randomized trials investigating intensive glucose control in critically ill adults. The primary outcome was in-hospital mortality. Secondary outcomes included survival to 90 days and time to live cessation of treatment with vasopressors or inotropes, mechanical ventilation, and newly commenced renal replacement. Severe hypoglycemia was a safety outcome. RESULTS Of 38 eligible trials (n=29,537 participants), 20 (n=14,171 participants) provided individual patient data including in-hospital mortality status for 7059 and 7049 participants allocated to intensive and conventional glucose control, respectively. Of these 1930 (27.3%) and 1891 (26.8%) individuals assigned to intensive and conventional control, respectively, died (risk ratio, 1.02; 95% confidence interval [CI], 0.96 to 1.07; P=0.52; moderate certainty). There was no apparent heterogeneity of treatment effect on in-hospital mortality in any examined subgroups. Intensive glucose control increased the risk of severe hypoglycemia (risk ratio, 3.38; 95% CI, 2.99 to 3.83; P<0.0001). CONCLUSIONS Intensive glucose control was not associated with reduced mortality risk but increased the risk of severe hypoglycemia. We did not identify a subgroup of patients in whom intensive glucose control was beneficial.

UR - https://go.openathens.net/redirector/westernsydney.edu.au?url=https://doi.org/10.1056/evidoa2400082

U2 - 10.1056/EVIDoa2400082

DO - 10.1056/EVIDoa2400082

M3 - Article

SN - 2766-5526

VL - 3

JO - NEJM Evidence

JF - NEJM Evidence

IS - 8

ER -

A Patient-Level Meta-Analysis of Intensive Glucose Control in Critically Ill Adults

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