Cardiac arrest: out-of-hospital: high-dose epinephrine did not increase survival at 24 hours

Clinical bottom line (level 1b)

  1. Patients with an out-of-hospital cardiac arrest who received high-dose epinephrine compared with standard dose were more likely to regain spontaneous circulation (NNT = 25 at minutes) .
  2. Patients who receive high-dose epinephrine are not more likely to be alive after 24 hours.
  3. There is no clear effect on survival to discharge, or discharge without neurological impairment.
Gueugniaud et al: New England Journal of Medicine 1998; 339: 1595-1601
Expires November 2003

The study

Unblinded ?concealed randomised trial with intention-to-treat
Setting: 12 cities in France and Belgium

3327 patients (aged 18 to 92; mean 65, 70% male) with an out-of-hospital cardiac arrest (absence of spontaneous respiration and palpable pulse) - 74% in asystole, 14% in pulseless electrical activity)

Excluded if
  • epinephrine injected before enrolment
  • return of spontaneous circulation for a VF cardiac arrest within 3 countershocks
  • aged < 18
  • traumatic cardiac arrest
  • obvious signs of irreversible cardiac arrest


    • Note:
  • Patients were treated according to American Heart Association and European Resuscitation Council guidelines, except for epinephrine dosing.


    • Control Group: (n = 1650, 1650 analysed): epinephrine 1 mg every 3 minutes
    Experimental Group: (n = 1677, 1677 analysed): epinephrine 5 mg every 3 minutes (up to 15 dose)

    100% followed for ? length of hospital stay
    Outcome notes:
    • survival : at 24 hours

    The evidence

    Outcome Time to outcome CEREERRRR
    (95% CI)    		ARR
    (95% CI)    		NNT
    (95% CI)
    return of spontaneous circulation minutes 601
    (36.42%)    		 678
    (40.43%)    		 11%
    (2% to 21%)    		 4.01%
    (0.70% to 7.31%)    		 25
    (14 to 142)
    admission to hospital 24 minutes 389
    (23.58%)    		 444
    (26.48%)    		 12%
    (0.00% to 26%)    		 2.88%
    (0.06% to 5.84%)    		 35
    (NNT = 17 to infinity;
    NNH = 1762 to infinity)
    survival 24 hours 263
    (15.94%)    		 272
    (16.21%)    		 2%
    (-13% to 19%)    		 0.28%
    (-2.2% to 2.77%)    		 370
    (NNT = 36 to infinity;
    NNH = 45 to infinity)
    discharge from hospital days 46
    (2.79%)    		 38
    (2.26%)    		 -19%
    (-47% to 24%)    		 -0.52%
    (-1.59% to 0.54%)    		 -191
    (NNT = 184 to infinity;
    NNH = 63 to infinity)
    discharged without neurological impairment days 26
    (1.58%)    		 26
    (1.55%)    		 -2%
    (-43% to 69%)    		 -0.03%
    (-0.87% to 0.82%)    		 -3803
    (NNT = 115 to infinity;
    NNH = 122 to infinity)

    Comments

    1. The study is too small to comment on the effect of high-dose epinephrine on survival to discharge or survival without neurological impairment.
    2. 42/564 patients in ventricular fibrillation survived to discharge (7.5%: 95% CI: 5.3% to 9.6%).
    3. 13/316 patients in PEA survived to discharge (4.1%: 95% CI: 1.9% to 6.3%).
    4. 31/2447 patients in asystole survived to discharge (1.3%: 95% CI: 0.8% to 1.7%)

    Citation

    1. Gueugniaud P-Y, Mols P, Goldstein P, et al: A comparison of repeated high doses and repeated standard doses of epinephrine for cardiac arrest outside the hospital. New England Journal of Medicine 1998; 339: 1595-1601
    Search Terms: arrest in Cochrane
    Contributor: Chris Ball and Musab Hayatli, November 1999
    Reviewer: William Rhoton

    Clinical Question.
    Patient out-of-hospital cardiac arrest
    Intervention or Exposure high-dose epinephrine
    Comparison standard dose epinephrine
    Outcome survival