Flumazenil in mixed drug intoxications
Date First Published:
June 3, 2019
Last Updated:
June 4, 2019
Report by:
Dr. Syed Mehboob Mazhar, ST2 Emergency Medicine (Ipswich hospital)
Search checked by:
Dr. Jonathan Griffiths, Ipswich hospital
Three-Part Question:
In [a patient with suspected benzodiazepine and mixed drug overdose] does [administration of flumazenil cause improvement in consciousness level] and [does it cause clinically significant adverse effects]
Clinical Scenario:
Young lady has presented with overdose to the emergency department. She is drowsy at presentation and is suspected to have a mixed overdose of medications. Her urine toxicology screen is positive for benzodiazepines.
Search Strategy:
Medline using ovid interface and Pubmed
{exp [benzodiazepine] and [mixed drug overdose] and [flumazenil]}
{exp [benzodiazepine] and [mixed drug overdose] and [flumazenil]}
Search Details:
42 papers were found
Outcome:
42 papers were found out of which 37 were found irrelevant to all three study questions
Relevant Paper(s):
| Study Title | Patient Group | Study type (level of evidence) | Outcomes | Key results | Study Weaknesses |
|---|---|---|---|---|---|
| Should a benzodiazepine antagonist be used in unconscious patients presenting to the emergency department? 3.tAdeline Su-Yin Ngo, Charles Rabind Anthony, Miny Samuel, Evelyn Wong, R. Ponampalam , 5 September 2006. Singapore | Adults and children in emergency department and intensive care with a low GCS and suspected drug overdose | Systematic review of randomized control trials | Improvement in consciousness level within 5 minutes of intervention | Flumazenil was found to reverse coma of suspected drug poisoning with a relative benefit of 4.45 (95% CI 2.65-7.45) | No uniformity in flumazenil dosage used Lack of uniformity in reporting GCS Total sample size of pooled sample could be insufficient to demonstrate risks |
| Any major side effects (death, seizure, collapse and arrhythmia) | There was no statistical difference in major side effects between flumazenil and a placebo. | ||||
| Clinical experiences with Ro 15-1788 (Anexate) in benzodiazepine and mixed-drug overdoses R Fantozzi, L Caramelli, M Barattini, P Bott, F Ledda, F moronic, S Peruzzi, AM Zorn, PF Mannaioni. 1988 | 12 Comatosed patients with benzodiazepine overdose and 10 with mixed overdose | Prospective interventional study | Reversal of coma in patients with suspected benzodiapine and mixed drug overdoses | Drug Ro 15-1788 led to reversal of coma in patients with grade 1 coma | Small sample size was too small Lack of randomization or blinding |
| Risks and Benefits of Therapy with Flumazenil (Anexate) in Mixed Drug Intoxications. 5.tE.Geller, P. Crome, M.D. Schaller, B Marchant, M Ectors, G. ScolloLavizzari. 1991 | Case reports of mixed drug overdoses from 4 countries between 1982-1986 | Case series | Epidemiology of mixed drug overdoses with particular reference to overdoses with benzodiazepine and tricyclic antidepressants | flumazenil should not replace appropriate primary care | |
| flumazenil treatment is initiated | |||||
| hypoxemia, airway obstruction, severe hypotension and/or significant arrhythmias must be corrected before | |||||
| flumazenil should be used with caution in patients with a known history of seizure disorder before treatment and TCA overdose | |||||
| flumazenil should not be administered by inexperienced persons | |||||
| Fatal Seizures after Flumazenil Administration in a Patient with Mixed Overdose Gregory P. Haverkos, Raymond P. DiSalvo, Thomas E. Imhoff. 1994 | 1 patient with mixed overdose of benzodiazepine and tricyclic antidepressants | Case report | Caution must be exercised when administering flumazenil to patients with risk factors | Low level of evidence. | |
| If flumazenil causes seizures, the patient would require subsequently high doses of benzodiazepines | |||||
| Flumazenil and seizures: analysis of 43 cases. Spivey. 1992 | 43 patients who developed seizures after administration of flumazenil | Case series | Analysis of 43 cases of seizures with flumazenil recorded to date | Seizures though not a direct effect of flumazenil could be related to reversal of benzodiazepine effect. Certain identifiable groups with high risk of seizure activity should be administered flumazenil with caution. |
Author Commentary:
Flumazenil has been found to improve the Glasgow coma score in patients with mixed overdose and there has been no significant difference in adverse effects between flumazenil and placebo. However, there have been several case reports demonstrating seizures in certain high risk groups which include patients with seizure disorder, tricyclic antidepressants overdose. Further studies are needed to evaluate if flumazenil would reduce interventions in emergency departments
Bottom Line:
Flumazenil can be used in patients with suspected benzodiazepine and mixed drug overdose though the clinical significance of the drug is questionable. It should be used with caution in high risk groups (seizure disorder and tricyclic antidepressants overdose) and they can be suspected by QRS prolongation, acidosis and history. In these cases it might be safer to symptomatically treat the patients rather than fully reversing the effects of benzodiazepines.
References:
- 3.tAdeline Su-Yin Ngo, Charles Rabind Anthony, Miny Samuel, Evelyn Wong, R. Ponampalam . Should a benzodiazepine antagonist be used in unconscious patients presenting to the emergency department?
- R Fantozzi, L Caramelli, M Barattini, P Bott, F Ledda, F moronic, S Peruzzi, AM Zorn, PF Mannaioni. . Clinical experiences with Ro 15-1788 (Anexate) in benzodiazepine and mixed-drug overdoses
- 5.tE.Geller, P. Crome, M.D. Schaller, B Marchant, M Ectors, G. ScolloLavizzari. . Risks and Benefits of Therapy with Flumazenil (Anexate) in Mixed Drug Intoxications.
- Gregory P. Haverkos, Raymond P. DiSalvo, Thomas E. Imhoff. . Fatal Seizures after Flumazenil Administration in a Patient with Mixed Overdose
- Spivey. . Flumazenil and seizures: analysis of 43 cases.