title: Out-of-hospital administration of intravenous glucose-insulin-potassium in patients with suspected acute coronary syndromes: the IMMEDIATE randomized controlled trial.
abstract: BACKGROUND
  Laboratory studies suggest that in the setting of cardiac ischemia, immediate intravenous glucose-insulin-potassium (GIK) reduces ischemia-related arrhythmias and myocardial injury. Clinical trials have not consistently shown these benefits, possibly due to delayed administration.
  
  
  OBJECTIVE
  To test out-of hospital emergency medical service (EMS) administration of GIK in the first hours of suspected acute coronary syndromes (ACS).
  
  
  METHODS
  Randomized, placebo-controlled, double-blind effectiveness trial in 13 US cities (36 EMS agencies), from December 2006 through July 31, 2011, in which paramedics, aided by electrocardiograph (ECG)-based decision support, randomized 911 (871 enrolled) patients (mean age, 63.6 years; 71.0% men) with high probability of ACS.
  
  
  METHODS
  Intravenous GIK solution (n = 411) or identical-appearing 5% glucose placebo (n = 460) administered by paramedics in the out-of-hospital setting and continued for 12 hours.
  
  
  METHODS
  The prespecified primary end point was progression of ACS to myocardial infarction (MI) within 24 hours, as assessed by biomarkers and ECG evidence. Prespecified secondary end points included survival at 30 days and a composite of prehospital or in-hospital cardiac arrest or in-hospital mortality, analyzed by intent-to-treat and by presentation with ST-segment elevation.
  
  
  RESULTS
  There was no significant difference in the rate of progression to MI among patients who received GIK (n = 200; 48.7%) vs those who received placebo (n = 242; 52.6%) (odds ratio [OR], 0.88; 95% CI, 0.66-1.13; P = .28). Thirty-day mortality was 4.4% with GIK vs 6.1% with placebo (hazard ratio [HR], 0.72; 95% CI, 0.40-1.29; P = .27). The composite of cardiac arrest or in-hospital mortality occurred in 4.4% with GIK vs 8.7% with placebo (OR, 0.48; 95% CI, 0.27-0.85; P = .01). Among patients with ST-segment elevation (163 with GIK and 194 with placebo), progression to MI was 85.3% with GIK vs 88.7% with placebo (OR, 0.74; 95% CI, 0.40-1.38; P = .34); 30-day mortality was 4.9% with GIK vs 7.7% with placebo (HR, 0.63; 95% CI, 0.27-1.49; P = .29). The composite outcome of cardiac arrest or in-hospital mortality was 6.1% with GIK vs 14.4% with placebo (OR, 0.39; 95% CI, 0.18-0.82; P = .01). Serious adverse events occurred in 6.8% (n = 28) with GIK vs 8.9% (n = 41) with placebo (P = .26).
  
  
  CONCLUSIONS
  Among patients with suspected ACS, out-of-hospital administration of intravenous GIK, compared with glucose placebo, did not reduce progression to MI. Compared with placebo, GIK administration was not associated with improvement in 30-day survival but was associated with lower rates of the composite outcome of cardiac arrest or in-hospital mortality.
  
  
  BACKGROUND
  clinicaltrials.gov Identifier: NCT00091507.
authors.affiliation: Institute for Clinical Research and Health Policy Studies, Tufts Medical Center and Tufts University School of Medicine, Boston, Massachusetts 02111, USA. hselker@tuftsmedicalcenter.org
authors.forename: Harry P
authors.initials: HP
authors.lastname: Selker
authors.forename: Joni R
authors.initials: JR
authors.lastname: Beshansky
authors.forename: Patricia R
authors.initials: PR
authors.lastname: Sheehan
authors.forename: Joseph M
authors.initials: JM
authors.lastname: Massaro
authors.forename: John L
authors.initials: JL
authors.lastname: Griffith
authors.forename: Ralph B
authors.initials: RB
authors.lastname: D'Agostino
authors.forename: Robin
authors.initials: R
authors.lastname: Ruthazer
authors.forename: James M
authors.initials: JM
authors.lastname: Atkins
authors.forename: Assaad J
authors.initials: AJ
authors.lastname: Sayah
authors.forename: Michael K
authors.initials: MK
authors.lastname: Levy
authors.forename: Michael E
authors.initials: ME
authors.lastname: Richards
authors.forename: Tom P
authors.initials: TP
authors.lastname: Aufderheide
authors.forename: Darren A
authors.initials: DA
authors.lastname: Braude
authors.forename: Ronald G
authors.initials: RG
authors.lastname: Pirrallo
authors.forename: Delanor D
authors.initials: DD
authors.lastname: Doyle
authors.forename: Ralph J
authors.initials: RJ
authors.lastname: Frascone
authors.forename: Donald J
authors.initials: DJ
authors.lastname: Kosiak
authors.forename: James M
authors.initials: JM
authors.lastname: Leaming
authors.forename: Carin M
authors.initials: CM
authors.lastname: Van Gelder
authors.forename: Gert-Paul
authors.initials: GP
authors.lastname: Walter
authors.forename: Marvin A
authors.initials: MA
authors.lastname: Wayne
authors.forename: Robert H
authors.initials: RH
authors.lastname: Woolard
authors.forename: Lionel H
authors.initials: LH
authors.lastname: Opie
authors.forename: Charles E
authors.initials: CE
authors.lastname: Rackley
authors.forename: Carl S
authors.initials: CS
authors.lastname: Apstein
authors.forename: James E
authors.initials: JE
authors.lastname: Udelson
mesh_terms: D054058:Acute Coronary Syndrome / Q000188:drug therapy* / Q000401:mortality; D000368:Aged; D000488:Allied Health Personnel; D000789:Angina, Unstable / Q000150:complications / Q000188:drug therapy; D002314:Cardioplegic Solutions / Q000627:therapeutic use*; D003661:Decision Support Techniques; D004311:Double-Blind Method; D004562:Electrocardiography; D004632:Emergency Medical Services; D005260:Female; D005947:Glucose / Q000627:therapeutic use; D006323:Heart Arrest / Q000517:prevention & control; D017052:Hospital Mortality; D006801:Humans; D007328:Insulin / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000209:etiology / Q000517:prevention & control*; D016017:Odds Ratio; D011188:Potassium / Q000627:therapeutic use; D016019:Survival Analysis; D016896:Treatment Outcome
chemical_list: D002314:Cardioplegic Solutions; D007328:Insulin; C030396:glucose-insulin-potassium cardioplegic solution; D005947:Glucose; D011188:Potassium