title: Severe and multiple hypoglycemic episodes are associated with increased risk of death in ICU patients.
abstract: BACKGROUND
  In a randomized controlled trial comparing tight glucose control with a computerized decision support system and conventional protocols (post hoc analysis), we tested the hypothesis that hypoglycemia is associated with a poor outcome, even when controlling for initial severity.
  
  
  METHODS
  We looked for moderate (2.2 to 3.3 mmol/L) and severe (<2.2 mmol/L) hypoglycemia, multiple hypoglycemic events (n ≥3) and the other main components of glycemic control (mean blood glucose level and blood glucose coefficient of variation (CV)). The primary endpoint was 90-day mortality. We used both a multivariable analysis taking into account only variables observed at admission and a multivariable matching process (greedy matching algorithm; caliper width of 10(-5) digit with no replacement).
  
  
  RESULTS
  A total of 2,601 patients were analyzed and divided into three groups: no hypoglycemia (n =1,474), moderate hypoglycemia (n =874, 34%) and severe hypoglycemia (n =253, 10%). Patients with moderate or severe hypoglycemia had a poorer prognosis, as shown by a higher mortality rate (36% and 54%, respectively, vs. 28%) and decreased number of treatment-free days. In the multivariable analysis, severe (odds ratio (OR), 1.50; 95% CI, 1.36 to 1.56; P =0.043) and multiple hypoglycemic events (OR, 1.76, 95% CI, 1.31 to 3.37; P <0.001) were significantly associated with mortality, whereas blood glucose CV was not. Using multivariable matching, patients with severe (53% vs. 35%; P <0.001), moderate (33% vs. 27%; P =0.029) and multiple hypoglycemic events (46% vs. 32%, P <0.001) had a higher 90-day mortality.
  
  
  CONCLUSIONS
  In a large cohort of ICU patients, severe hypoglycemia and multiple hypoglycemic events were associated with increased 90-day mortality.
  
  
  BACKGROUND
  Clinicaltrials.gov Identifier: NCT01002482 . Registered 26 October 2009.
authors.affiliation: Service de Réanimation polyvalente, Hôpital Louis Pasteur, CH de Chartres, 34 , avenue du Docteur Maunoury, 28000, Chartres, France. pkalfon@ch-chartres.fr.
authors.forename: Pierre
authors.initials: P
authors.lastname: Kalfon
authors.affiliation: Departments of Anesthesia & Clinical Epidemiology and Biostatistics, Michael G DeGroote School of Medicine, Faculty of Health Sciences, McMaster University, Hamilton, ON, Canada. yannick.lemanach@phri.ca.
authors.forename: Yannick
authors.initials: Y
authors.lastname: Le Manach
authors.affiliation: Service de Réanimation médico-chirurgicale, Hôpital Saint-Roch, CHU de Nice, 5, rue Pierre Dévoluy, CS 91179, 06001 Nice Cedex 1, France and IRCAN Unit, UMR INSERM U1081-CNRS 7284, Nice-Sophia Antipolis University, Nice, France. ichai@unice.fr.
authors.forename: Carole
authors.initials: C
authors.lastname: Ichai
authors.affiliation: Service de Réanimation médicale, Institut de Cardiologie, CHU Pitié-Salpêtrière, Assistance Publique- Hôpitaux de Paris (AP-HP), 47 bd de l'Hôpital, 75651, Paris cedex 13, France. nicolas.brechot@psl.aphp.fr.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Bréchot
authors.affiliation: Service de Réanimation chirurgicale-Brûlés PTMC, Hôtel Dieu, CHU de Nantes, Place Alexis Ricordeau, 44093, Nantes cedex 1, France. raphael.cinotti@chu-nantes.fr.
authors.forename: Raphaël
authors.initials: R
authors.lastname: Cinotti
authors.affiliation: Service de Réanimation médicale, Hôpital Bretonneau, CHRU de Tours, 2, boulevard Tonnellé, 37044, Tours cedex 9, France. dequin@med.univ-tours.fr.
authors.forename: Pierre-François
authors.initials: PF
authors.lastname: Dequin
authors.affiliation: Service de Réanimation polyvalente, Hôpital Purpan, CHU de Toulouse, Place du Docteur Baylac TSA 40031, 31059, Toulouse cedex 9, France. riu.b@chu-toulouse.fr.
authors.forename: Béatrice
authors.initials: B
authors.lastname: Riu-Poulenc
authors.affiliation: Département d'Anesthésie et Réanimation chirurgicale, CHU Bichat-Claude Bernard, AP-HP, 46 Rue Henri Huchard, 75018, Paris, France. philippe.montravers@bch.aphp.fr.
authors.forename: Philippe
authors.initials: P
authors.lastname: Montravers
authors.affiliation: Service de Réanimation, CHU Raymond Poincaré, AP-HP, 104 Boulevard Raymond Poincaré, 92380, Garches, France. djillali.annane@rpc.aphp.fr.
authors.forename: Djilalli
authors.initials: D
authors.lastname: Annane
authors.affiliation: Service d'Anesthésie Réanimation, Hôpital Nord, CHRU Amiens, Place Victor Pauchet, 80054, Amiens Cedex 1, France. dupont.herve@chu-amiens.fr.
authors.forename: Hervé
authors.initials: H
authors.lastname: Dupont
authors.affiliation: Institut National de Recherche en Informatique et en Automatique (INRIA), Domaine de Voluceau, Rocquencourt, B.P. 105, 78153, Le Chesnay, France. michel.sorine@inria.fr.
authors.forename: Michel
authors.initials: M
authors.lastname: Sorine
authors.affiliation: Service d'accueil des Urgences, CHU Pitié-Salpêtrière AP-HP, 47 bd de l'Hôpital, 75651, Paris cedex 13, France. bruno.riou@psl.aphp.fr.|Sorbonne Université, UPMC Univ Paris 6, UMR INSERM 1166, Paris, France. bruno.riou@psl.aphp.fr.
authors.forename: Bruno
authors.initials: B
authors.lastname: Riou
mesh_terms: D001786:Blood Glucose / Q000032:analysis; D004360:Drug Therapy, Computer-Assisted; D005260:Female; D017052:Hospital Mortality; D006801:Humans; D006943:Hyperglycemia / Q000188:drug therapy / Q000503:physiopathology; D007003:Hypoglycemia / Q000401:mortality*; D007004:Hypoglycemic Agents / Q000008:administration & dosage; D007328:Insulin / Q000008:administration & dosage; D007362:Intensive Care Units; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D012720:Severity of Illness Index; D013312:Stress, Physiological / Q000502:physiology
chemical_list: D001786:Blood Glucose; D007004:Hypoglycemic Agents; D007328:Insulin