1. Lancet. 2018 Jul 7;392(10141):31-40. doi: 10.1016/S0140-6736(18)31080-8. Epub
2018 Jun 14.

Sodium bicarbonate therapy for patients with severe metabolic acidaemia in the
intensive care unit (BICAR-ICU): a multicentre, open-label, randomised
controlled, phase 3 trial.

Jaber S(1), Paugam C(2), Futier E(3), Lefrant JY(4), Lasocki S(5), Lescot T(6),
Pottecher J(7), Demoule A(8), Ferrandière M(9), Asehnoune K(10), Dellamonica
J(11), Velly L(12), Abback PS(2), de Jong A(13), Brunot V(14), Belafia F(13),
Roquilly A(10), Chanques G(13), Muller L(4), Constantin JM(3), Bertet H(15),
Klouche K(14), Molinari N(15), Jung B(14); BICAR-ICU Study Group.

Collaborators: Jaber S, de Jong A, Belafia F, Chanques G, Monnin M, Delay JM,
Cissé M, Geniez M, Conseil M, Souche B, Paugam C, Abback PS, Futier E, Constantin
JM, Lefrant JY, Muller L, Lasocki S, Lescot T, Pottecher J, Noll E, Demoule A,
Morawiec E, Ferrandière M, Asehnoune K, Roquilly A, Dellamonica J, Robert A,
Velly L, Triglia T, Brunot V, Molinari N, Mechati M, Arnal JM, Durand-Gasselin J,
Demoly D, Hraiech S, Papazian L, Gilles V, Rimmelé T, Riu B, Cougot P, Fourcade
O, Seguin P, Charbit J, Capdevila X, Leone M, Zieleskiewicz L, Ichai C, Orban JC,
Darmon M, Azoulay E, Lemiale V, Zafrani L, Debbat K, Mimoz O, Guérin C, Kipnis E.

Author information: 
(1)Saint Eloi ICU, Montpellier University Hospital, PhyMedExp, INSERM, CNRS,
Montpellier, France. Electronic address: s-jaber@chu-montpellier.fr.
(2)AP-HP, Département Anesthésie et Réanimation, Hôpital Beaujon, Hôpitaux
Universitaires Paris Nord Val de Seine, Paris, France.
(3)CHU de Clermont-Ferrand, Department of Perioperative Medicine, GReD,
UMR/CNRS6293, University Clermont Auvergne, INSERM U1103, Clermont-Ferrand,
France.
(4)CHU de Nîmes, Département Anesthésie et Réanimation, University of
Montpellier-Nîmes, Nîmes, France.
(5)CHU d'Angers, Réanimation Chirurgicale, Angers, France.
(6)AP-HP, Département Anesthésie et Réanimation, Hôpital Saint Antoine, Paris,
France.
(7)Hôpitaux Universitaires de Strasbourg, Service d'Anesthésie-Réanimation
Chirurgicale-Université de Strasbourg, Fédération de Médecine Translationnelle de
Strasbourg, Strasbourg, France.
(8)Service de Pneumologie, Sorbonne Université, INSERM, UMRS1158 Neurophysiologie
Respiratoire Expérimentale et Clinique, Paris, France; AP-HP, Groupe Hospitalier 
Pitié-Salpêtrière Charles Foix, Service de Pneumologie et Réanimation Médicale du
Département R3S, Paris, France.
(9)CHU de Tours, Réanimation Chirurgicale, Tours, France.
(10)CHU de Nantes, Département Anesthésie et Réanimation Chirurgicale, Nantes,
France.
(11)CHU de Nice, Département de Réanimation Médicale, INSERM-C3M-Université Cote 
d'Azur, Nice, France.
(12)Aix-Marseille Université, AP-HM, Département Anesthésie et Réanimation
Chirurgicale, Groupe Hospitalier Timone, UMR 7289, CNRS, Marseille, France.
(13)Saint Eloi ICU, Montpellier University Hospital, PhyMedExp, INSERM, CNRS,
Montpellier, France.
(14)Département de Médecine Intensive et Réanimation, Montpellier University
Hospital, PhyMedExp, INSERM, CNRS, Montpellier, France.
(15)CHU de Montpellier, Department of Statistics, Montpellier University,
Montpellier, France.

Erratum in
    Lancet. 2018 Dec 8;392(10163):2440.

Comment in
    Lancet. 2018 Jul 7;392(10141):3-4.

BACKGROUND: Acute acidaemia is frequently observed during critical illness.
Sodium bicarbonate infusion for the treatment of severe metabolic acidaemia is a 
possible treatment option but remains controversial, as no studies to date have
examined its effect on clinical outcomes. Therefore, we aimed to evaluate whether
sodium bicarbonate infusion would improve these outcomes in critically ill
patients.
METHODS: We did a multicentre, open-label, randomised controlled, phase 3 trial. 
Local investigators screened eligible patients from 26 intensive care units
(ICUs) in France. We included adult patients (aged ≥18 years) who were admitted
within 48 h to the ICU with severe acidaemia (pH ≤7·20, PaCO2 ≤45 mm Hg, and
sodium bicarbonate concentration ≤20 mmol/L) and with a total Sequential Organ
Failure Assessment score of 4 or more or an arterial lactate concentration of 2
mmol/L or more. We randomly assigned patients (1:1), by stratified randomisation 
with minimisation via a restricted web platform, to receive either no sodium
bicarbonate (control group) or 4·2% of intravenous sodium bicarbonate infusion
(bicarbonate group) to maintain the arterial pH above 7·30. Our protocol
recommended that the volume of each infusion should be within the range of
125-250 mL in 30 min, with a maximum of 1000 mL within 24 h after inclusion.
Randomisation criteria were stratified among three prespecified strata: age,
sepsis status, and the Acute Kidney Injury Network (AKIN) score. The primary
outcome was a composite of death from any cause by day 28 and the presence of at 
least one organ failure at day 7. All analyses were done on data from the
intention-to-treat population, which included all patients who underwent
randomisation. This study is registered with ClinicalTrials.gov, number
NCT02476253.
FINDINGS: Between May 5, 2015, and May 7, 2017, we enrolled 389 patients into the
intention-to-treat analysis in the overall population (194 in the control group
and 195 in the bicarbonate group). The primary outcome occurred in 138 (71%) of
194 patients in the control group and 128 (66%) of 195 in the bicarbonate group
(absolute difference estimate -5·5%, 95% CI -15·2 to 4·2; p=0·24). The
Kaplan-Meier method estimate of the probability of survival at day 28 between the
control group and bicarbonate group was not significant (46% [95% CI 40-54] vs
55% [49-63]; p=0·09. In the prespecified AKIN stratum of patients with a score of
2 or 3, the Kaplan-Meier method estimate of survival by day 28 between the
control group and bicarbonate group was significant (37% [95% CI 28-48] vs 54%
[45-65]; p=0·0283). [corrected] Metabolic alkalosis, hypernatraemia, and
hypocalcaemia were observed more frequently in the bicarbonate group than in the 
control group, with no life-threatening complications reported.
INTERPRETATION: In patients with severe metabolic acidaemia, sodium bicarbonate
had no effect on the primary composite outcome. However, sodium bicarbonate
decreased the primary composite outcome and day 28 mortality in the a-priori
defined stratum of patients with acute kidney injury.
FUNDING: French Ministry of Health and the Société Française d'Anesthésie
Réanimation.

Copyright © 2018 Elsevier Ltd. All rights reserved.

DOI: 10.1016/S0140-6736(18)31080-8 
PMID: 29910040  [Indexed for MEDLINE]