Out-of-hospital administration of intravenous glucose-insulin-potassium in patients with suspected acute coronary syndromes: The IMMEDIATE randomized controlled trial

Harry P. Selker, Joni R. Beshansky, Patricia R. Sheehan, Joseph M. Massaro, John L. Griffith, Ralph B. D'Agostino, Robin Ruthazer, James M Atkins, Assaad J. Sayah, Michael K. Levy, Michael E. Richards, Tom P. Aufderheide, Darren A. Braude, Ronald G. Pirrallo, Delanor D. Doyle, Ralph J. Frascone, Donald J. Kosiak, James M. Leaming, Carin M. Van Gelder, Gert Paul WalterMarvin A. Wayne, Robert H. Woolard, Lionel H. Opie, Charles E. Rackley, Carl S. Apstein, James E. Udelson

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136 Citations (Scopus)

Abstract

Context: 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). Design, Setting, and Participants: Randomized, placebo-controlled, doubleblind 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. Intervention: 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. Main Outcome Measures: 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. Trial Registration: clinicaltrials.gov Identifier: NCT00091507.

Original languageEnglish (US)
Pages (from-to)1925-1933
Number of pages9
JournalJAMA - Journal of the American Medical Association
Volume307
Issue number18
DOIs
StatePublished - May 9 2012

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Hospital Administration
Acute Coronary Syndrome
Potassium
Randomized Controlled Trials
Placebos
Insulin
Glucose
Hospital Mortality
Heart Arrest
Odds Ratio
Myocardial Infarction
Allied Health Personnel
Emergency Medical Services
Electrocardiography
Ischemia
Survival
Mortality
Hospital Emergency Service
Cardiac Arrhythmias

ASJC Scopus subject areas

  • Medicine(all)

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Out-of-hospital administration of intravenous glucose-insulin-potassium in patients with suspected acute coronary syndromes : The IMMEDIATE randomized controlled trial. / Selker, Harry P.; Beshansky, Joni R.; Sheehan, Patricia R.; Massaro, Joseph M.; Griffith, John L.; D'Agostino, Ralph B.; Ruthazer, Robin; Atkins, James M; Sayah, Assaad J.; Levy, Michael K.; Richards, Michael E.; Aufderheide, Tom P.; Braude, Darren A.; Pirrallo, Ronald G.; Doyle, Delanor D.; Frascone, Ralph J.; Kosiak, Donald J.; Leaming, James M.; Van Gelder, Carin M.; Walter, Gert Paul; Wayne, Marvin A.; Woolard, Robert H.; Opie, Lionel H.; Rackley, Charles E.; Apstein, Carl S.; Udelson, James E.

In: JAMA - Journal of the American Medical Association, Vol. 307, No. 18, 09.05.2012, p. 1925-1933.

Research output: Contribution to journalArticle

Selker, HP, Beshansky, JR, Sheehan, PR, Massaro, JM, Griffith, JL, D'Agostino, RB, Ruthazer, R, Atkins, JM, Sayah, AJ, Levy, MK, Richards, ME, Aufderheide, TP, Braude, DA, Pirrallo, RG, Doyle, DD, Frascone, RJ, Kosiak, DJ, Leaming, JM, Van Gelder, CM, Walter, GP, Wayne, MA, Woolard, RH, Opie, LH, Rackley, CE, Apstein, CS & Udelson, JE 2012, 'Out-of-hospital administration of intravenous glucose-insulin-potassium in patients with suspected acute coronary syndromes: The IMMEDIATE randomized controlled trial', JAMA - Journal of the American Medical Association, vol. 307, no. 18, pp. 1925-1933. https://doi.org/10.1001/jama.2012.426
Selker, Harry P. ; Beshansky, Joni R. ; Sheehan, Patricia R. ; Massaro, Joseph M. ; Griffith, John L. ; D'Agostino, Ralph B. ; Ruthazer, Robin ; Atkins, James M ; Sayah, Assaad J. ; Levy, Michael K. ; Richards, Michael E. ; Aufderheide, Tom P. ; Braude, Darren A. ; Pirrallo, Ronald G. ; Doyle, Delanor D. ; Frascone, Ralph J. ; Kosiak, Donald J. ; Leaming, James M. ; Van Gelder, Carin M. ; Walter, Gert Paul ; Wayne, Marvin A. ; Woolard, Robert H. ; Opie, Lionel H. ; Rackley, Charles E. ; Apstein, Carl S. ; Udelson, James E. / Out-of-hospital administration of intravenous glucose-insulin-potassium in patients with suspected acute coronary syndromes : The IMMEDIATE randomized controlled trial. In: JAMA - Journal of the American Medical Association. 2012 ; Vol. 307, No. 18. pp. 1925-1933.
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title = "Out-of-hospital administration of intravenous glucose-insulin-potassium in patients with suspected acute coronary syndromes: The IMMEDIATE randomized controlled trial",
abstract = "Context: 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). Design, Setting, and Participants: Randomized, placebo-controlled, doubleblind 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. Intervention: 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. Main Outcome Measures: 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. Trial Registration: clinicaltrials.gov Identifier: NCT00091507.",
author = "Selker, {Harry P.} and Beshansky, {Joni R.} and Sheehan, {Patricia R.} and Massaro, {Joseph M.} and Griffith, {John L.} and D'Agostino, {Ralph B.} and Robin Ruthazer and Atkins, {James M} and Sayah, {Assaad J.} and Levy, {Michael K.} and Richards, {Michael E.} and Aufderheide, {Tom P.} and Braude, {Darren A.} and Pirrallo, {Ronald G.} and Doyle, {Delanor D.} and Frascone, {Ralph J.} and Kosiak, {Donald J.} and Leaming, {James M.} and {Van Gelder}, {Carin M.} and Walter, {Gert Paul} and Wayne, {Marvin A.} and Woolard, {Robert H.} and Opie, {Lionel H.} and Rackley, {Charles E.} and Apstein, {Carl S.} and Udelson, {James E.}",
year = "2012",
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day = "9",
doi = "10.1001/jama.2012.426",
language = "English (US)",
volume = "307",
pages = "1925--1933",
journal = "JAMA - Journal of the American Medical Association",
issn = "0098-7484",
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TY - JOUR

T1 - Out-of-hospital administration of intravenous glucose-insulin-potassium in patients with suspected acute coronary syndromes

T2 - The IMMEDIATE randomized controlled trial

AU - Selker, Harry P.

AU - Beshansky, Joni R.

AU - Sheehan, Patricia R.

AU - Massaro, Joseph M.

AU - Griffith, John L.

AU - D'Agostino, Ralph B.

AU - Ruthazer, Robin

AU - Atkins, James M

AU - Sayah, Assaad J.

AU - Levy, Michael K.

AU - Richards, Michael E.

AU - Aufderheide, Tom P.

AU - Braude, Darren A.

AU - Pirrallo, Ronald G.

AU - Doyle, Delanor D.

AU - Frascone, Ralph J.

AU - Kosiak, Donald J.

AU - Leaming, James M.

AU - Van Gelder, Carin M.

AU - Walter, Gert Paul

AU - Wayne, Marvin A.

AU - Woolard, Robert H.

AU - Opie, Lionel H.

AU - Rackley, Charles E.

AU - Apstein, Carl S.

AU - Udelson, James E.

PY - 2012/5/9

Y1 - 2012/5/9

N2 - Context: 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). Design, Setting, and Participants: Randomized, placebo-controlled, doubleblind 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. Intervention: 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. Main Outcome Measures: 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. Trial Registration: clinicaltrials.gov Identifier: NCT00091507.

AB - Context: 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). Design, Setting, and Participants: Randomized, placebo-controlled, doubleblind 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. Intervention: 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. Main Outcome Measures: 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. Trial Registration: clinicaltrials.gov Identifier: NCT00091507.

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