title: Bradycardia During Targeted Temperature Management: An Early Marker of Lower Mortality and Favorable Neurologic Outcome in Comatose Out-of-Hospital Cardiac Arrest Patients.
abstract: OBJECTIVE
  Bradycardia is common during targeted temperature management, likely being a physiologic response to lower body temperature, and has recently been associated with favorable outcome following out-of-hospital cardiac arrest in smaller observational studies. The present study sought to confirm this finding in a large multicenter cohort of patients treated with targeted temperature management at 33°C and explore the response to targeted temperature management targeting 36°C.
  
  
  METHODS
  Post hoc analysis of a prospective randomized study.
  
  
  METHODS
  Thirty-six ICUs in 10 countries.
  
  
  METHODS
  We studied 447 (targeted temperature management = 33°C) and 430 (targeted temperature management = 36°C) comatose out-of-hospital cardiac arrest patients with available heart rate data, randomly assigned in the targeted temperature management trial from 2010 to 2013.
  
  
  METHODS
  Targeted temperature management at 33°C and 36°C.
  
  
  RESULTS
  Endpoints were 180-day mortality and unfavorable neurologic function (cerebral performance category 3-5). Patients were stratified by target temperature and minimum heart rate during targeted temperature management (< 50, 50-59, and ≥ 60 beats/min [reference]) at 12, 20, and 28 hours after randomization. Heart rates less than 50 beats/min and 50-59 beats/min were recorded in 132 (30%) and 131 (29%) of the 33°C group, respectively. Crude 180-day mortality increased with increasing minimum heart rate (< 50 beats/min = 32%, 50-59 beats/min = 43%, and ≥ 60 beats/min = 60%; p(log-rank) < 0.0001). Bradycardia less than 50 beats/min was independently associated with lower 180-day mortality (hazard ratio(adjusted) = 0.50 [0.34-0.74; p < 0.001]) and lower odds of unfavorable neurologic outcome (odds ratio(adjusted) = 0.38 [ 0.21-0.68; p < 0.01]) in models adjusting for potential confounders including age, initial rhythm, time to return of spontaneous circulation, and lactate at admission. Similar, albeit less strong, independent associations of lower heart rates and favorable outcome were found in patients treated with targeted temperature management at 36°C.
  
  
  CONCLUSIONS
  This study confirms an independent association of bradycardia and lower mortality and favorable neurologic outcome in a large cohort of comatose out-of-hospital cardiac arrest patients treated by targeted temperature management at 33°C. Bradycardia during targeted temperature management at 33°C may thus be a novel, early marker of favorable outcome.
authors.affiliation: 1Department of Cardiology, The Heart Centre, Copenhagen University Hospital Rigshospitalet, Denmark. 2Department of Anesthesia and Intensive Care, Helsingborg Hospital, Helsingborg, Sweden. 3Department of Thoracic Anaesthesiology, The Heart Centre, Copenhagen University Hospital Rigshospitalet, Denmark. 4Department of Anaesthesia and Intensive Care, Santa Maria degli Angeli, Pordenone, Italy. 5Department of Intensive Care, Leeuwarden Medical Centrum, Leeuwarden, The Netherlands. 6Department of Cardiology, Lund University Hospital, Lund, Sweden. 7Department of Anesthesia and Intensive Care, Skåne University Hospital, Lund University, Lund, Sweden.
authors.forename: Jakob Hartvig
authors.initials: JH
authors.lastname: Thomsen
authors.forename: Niklas
authors.initials: N
authors.lastname: Nielsen
authors.forename: Christian
authors.initials: C
authors.lastname: Hassager
authors.forename: Michael
authors.initials: M
authors.lastname: Wanscher
authors.forename: Steen
authors.initials: S
authors.lastname: Pehrson
authors.forename: Lars
authors.initials: L
authors.lastname: Køber
authors.forename: John
authors.initials: J
authors.lastname: Bro-Jeppesen
authors.forename: Helle
authors.initials: H
authors.lastname: Søholm
authors.forename: Matilde
authors.initials: M
authors.lastname: Winther-Jensen
authors.forename: Tommaso
authors.initials: T
authors.lastname: Pellis
authors.forename: Michael
authors.initials: M
authors.lastname: Kuiper
authors.forename: David
authors.initials: D
authors.lastname: Erlinge
authors.forename: Hans
authors.initials: H
authors.lastname: Friberg
authors.forename: Jesper
authors.initials: J
authors.lastname: Kjaergaard
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers; D001831:Body Temperature; D001919:Bradycardia / Q000401:mortality* / Q000503:physiopathology; D003128:Coma / Q000209:etiology / Q000401:mortality*; D005260:Female; D006339:Heart Rate; D006801:Humans; D007036:Hypothermia, Induced / Q000401:mortality*; D007362:Intensive Care Units; D008297:Male; D008875:Middle Aged; D058687:Out-of-Hospital Cardiac Arrest / Q000150:complications / Q000401:mortality* / Q000628:therapy*; D011379:Prognosis; D011446:Prospective Studies
chemical_list: D015415:Biomarkers