Cardiac Arrest: Lidoflazine has no clear effect on cerebral function.

Clinical bottom line (level 1b-)

  1. Patients who are comatose after cardiac arrest who are given lidoflazine compared with placebo, showed no clear difference in cerebral function at 6 months.
  2. There is no effect on mortality.
Brain Resuscitation Clinical Trial II Study Group. : N Engl J Med 1991; 324: 1225-1231
Expires October 2003

The study

Double-blinded ?concealed randomised trial with intention-to-treat
Setting: 24 hospitals in Europe, Israel, USA

520 patients (aged range 12 to 95 years old; mean 62, 61% male) cardiac arrest with no purposeful motor response to pain after restoration of adequate spontaneous circulation and oxygenation

Excluded if
  • not seen within 30 minutes after restoration of adequate spontaneous circulation
  • resuscitation efforts were inappropriate (e.g. hopeless terminal condition)
  • awakened before randomisation
  • cardiac arrest due to primary intracranial disease (would affect neurological recovery)
  • coma caused by central nervous system depressant drugs (could protect brain) at time of arrest
  • hypothermia (rectal temperature <33 ° C at arrest time)
  • those given calcium entry blocker i.v. either during cardiac resuscitation or within first 24 hours after
  • <12 years old
  • atrial fibrillation or prolonged QT interval
  • women of childbearing age


    • Note:
  • If systolic blood pressure decreased below 90 mmHg or there were elevatons of central venous pressure or pulmonary-artery wedge pressure, development of congestive heart failure, conduction abnormalities and malignant arrhytmias or excessive vasopressor requirements, study infusion was temporarily stopped until investigator judged patient to be stable enough to continue.


    • Control Group: (n = 257, 257 analysed): Placebo; vehicle solution without active drug
    Experimental Group: (n = 259, 259 analysed): Lidoflazine-i.v. loading dose of 1 mg per kg body weight, plus additional i.v. doses of 0.25 mg per kg, 8 and 16 hours after resuscitation
    Lidoflazine was given as soon as possible after restoration of cardiovascular stability as shown by maintenance of systolic blood pressure >90 mmHg during a 5 minute observation period.
    99% followed for 6 months
    Outcome notes:
    • good cerebral recovery (categories 1 or 2) : measured with a modified five-point Glasgow coma scale; 1=conscious and alert, normal function or only slight disability; 2=conscious and alert with moderate disability; 3=conscious with severe disability; 4=comatose or persistent vegetative state; 5=brain-dead

    The evidence

    Outcome Time to outcome CEREERRRR
    (95% CI)    		ARR
    (95% CI)    		NNT
    (95% CI)
    good cerebral recovery (categories 1 or 2) 6 months 33
    (12.8%)    		 38
    (14.7%)    		 14%
    (-26% to 76%)    		 1.83%
    (-4.11% to 7.77%)    		 55
    (NNT = 13 to infinity;
    NNH = 24 to infinity)
    death 6 months 211
    (82.1%)    		 215
    (83.0%)    		 -1%
    (-9% to 7%)    		 -0.91%
    (-7.46% to 5.64%)    		 -110
    (NNT = 18 to infinity;
    NNH = 13 to infinity)

    Comments

    1. The study was too small to show any clear effect of lidoflazine.
    2. All patients were treated according to a standard therapy protocol aimed at optimising oxygen delivery to and minimising metabolic demand on the brain.

    Citation

    1. Brain Resuscitation Clinical Trial II Study Group. , : Randomized clinical study of a calcium-entry blocker (lidoflazine) in the treatment of comatose survivors of cardiac arrest.. N Engl J Med 1991; 324: 1225-1231
    Contributor: Clare Wotton & Chris Ball, October 1999
    Reviewer: Malcolm Daniel

    Clinical Question.
    Patient cardiac arrest
    Intervention or Exposure calcium-channel blockers
    Outcome survivors