title: Medication-induced and spontaneous hypoglycemia carry the same risk for hospital mortality in critically ill patients.
abstract: Hypoglycemia is associated with increased mortality, but the role of its etiology is unclear. This study aimed to examine the impact of hypoglycemia etiology on mortality risk among critically ill patients.
  
  
  
  This single-center, retrospective, cohort study evaluated adult patients admitted to the medical or surgical intensive care unit, who experienced medication-induced or spontaneous hypoglycemia (blood glucose <70 mg/dL) during intensive care unit admission. Patients who became hypoglycemic following receipt of glucose-lowering therapy within a predefined time period were categorized in the medication-induced group. Periods were determined for each agent based on expected pharmacokinetics in critically ill patients. Patients who became hypoglycemic with no identifiable cause were categorized in the spontaneous group. Primary analysis compared medication-induced and spontaneous hypoglycemia with a primary endpoint of all-cause hospital mortality. Secondary analyses stratified patients by diabetes, severity of hypoglycemia, and glycemic variability.
  
  
  
  A total of 642 patients were eligible for inclusion (305 medication-induced and 337 spontaneous). When adjusted for covariates, no difference in hospital mortality was observed based on hypoglycemia etiology (odds ratio, 1.22 [0.77-1.93]; P=.39). Regardless of etiology, hypoglycemic severity, frequency, and glycemic variability were significantly associated with higher odds of hospital mortality. Hypoglycemic etiology did not impact hospital mortality when patients were stratified by presence or absence of diabetes.
  
  
  
  Medication-induced hypoglycemia appears to be equally harmful as spontaneous hypoglycemia during critical illness. Future studies should aim to identify strategies to minimize hypoglycemia regardless of etiology, while also minimizing glycemic variability associated with hypoglycemia treatment.
authors.affiliation: Department of Pharmacy, The Ohio State University Wexner Medical Center, Columbus, OH.
authors.forename: Lina
authors.initials: L
authors.lastname: Saliba
authors.affiliation: Department of Surgery, Beth Israel Deaconess Medical Center & Harvard Medical School, Boston, MA.
authors.forename: Charles H
authors.initials: CH
authors.lastname: Cook
authors.affiliation: Department of Endocrinology, Diabetes & Metabolism, The Ohio State University Wexner Medical Center, Columbus, OH.
authors.forename: Kathleen M
authors.initials: KM
authors.lastname: Dungan
authors.affiliation: Center for Biostatistics, The Ohio State University, Columbus, OH.
authors.forename: Kyle
authors.initials: K
authors.lastname: Porter
authors.affiliation: Department of Pharmacy, The Ohio State University Wexner Medical Center, Columbus, OH. Electronic address: claire.murphy@osumc.edu.
authors.forename: Claire V
authors.initials: CV
authors.lastname: Murphy
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001786:Blood Glucose / Q000032:analysis; D015331:Cohort Studies; D003422:Critical Care; D016638:Critical Illness / Q000401:mortality*; D005260:Female; D017052:Hospital Mortality; D006801:Humans; D007003:Hypoglycemia / Q000139:chemically induced / Q000209:etiology / Q000401:mortality*; D007004:Hypoglycemic Agents / Q000009:adverse effects*; D007362:Intensive Care Units; D008297:Male; D008875:Middle Aged; D009820:Ohio; D012189:Retrospective Studies; D012307:Risk Factors; D055815:Young Adult
chemical_list: D001786:Blood Glucose; D007004:Hypoglycemic Agents
keywords: Blood glucose; Hypoglycemia; Iatrogenic disease; Insulin; Intensive care; Mortality