Coma: flumazenil reversed drug overdose.

Clinical bottom line (level 1b)

  1. Patients with drug overdose who were given flumazenil, were more likely to become fully conscious than those given placebo.
Weinbroum et al: Critical Care Medicine 1996; 24 (2): 199-206
Expires November 2003

The study

Double-blinded ?concealed randomised trial with intention-to-treat
Setting: general hospital , Israel

31 patients (aged mean 57 years, 52% female) suspected drug overdose, based on history, physical examination or information obtained from accompanying persons

Excluded if
  • <18 years old
  • pregnant women
  • suspected brain trauma
  • coma grade (defined by Matthew and Lawson scale) of 0 (fully conscious) or 1 (drowsy but reawakens to verbal commands)


    • Control Group: (n = 14, 14 analysed): 10 mL saline injected intravenously at a rate of 1 mL every 30 seconds
    Experimental Group: (n = 17, 17 analysed): 1 mg flumazenil in 10 mL saline. Injected intravenously at a rate of 1 mL every 30 seconds until the patient woke up or the 10 mL had been used
    Patients received supplemental oxygen by mask if they were breathing spontaneously on arrival at ICU. Endotracheal intubation was performed whenever deemed necessary and synchronised intermittent mandatory ventilation was initiated as required. Each patient was connected to an electrocardiogram monitor. A peripheral intravenous cannula was inserted through which a solution of 5% dextrose in 0.45% sodium chloride was infused. A central venous catheter was inserted and vasoactive drugs (eg. dopamine, ephedrine) were administered whenever blood pressure was below normal despite adequate fluid load, or when urine output was <0.5 mL per kg per minute. Patients received 30 g of activated charcoal every 4 hours until fully awakened, and sodium bicarbonate was given for alkalisation of the blood in patients with tricyclic overdose and alkalisation of the urine in barbiturate overdose.
    100% followed for ?
    Outcome notes:
    • full awakening : defined as 0 on the Matthew and Lawson scale

    The evidence

    Outcome Time to outcome CEREERRRR
    (95% CI)    		ARR
    (95% CI)    		NNT
    (95% CI)
    full awakening unknown 1
    (7.14%)    		 14
    (82.4%)    		 -1053%
    (-7620% to -72.0%)    		 -75.2%
    (-97.8% to -52.6%)    		 1
    (1 to 2)

    Comments

    1. Following the double-blind part of the trial, the authors switched it to an open trial due to the obvious effectiveness of flumazenil.
    2. Four patients given flumazenil suffered restlessness as a side effect compared with one in the placebo group; one in the flumazenil group suffered aggression and one crying compared with none in the placebo group.

    Citation

    1. Weinbroum A, Rudick V, Sorkine P, et al: Use of flumazenil in the treatment of drug overdose: A double-blind and open clinical study in 110 patients. Critical Care Medicine 1996; 24 (2): 199-206
    Contributor: Clare Wotton and Bob Phillips, November 1999
    Reviewer:

    Clinical Question.
    Patient drug overdose
    Intervention or Exposure flumazenil
    Comparison placebo
    Outcome waking from coma