Flumazenil and suspected benzodiazepine overdose
Date First Published:
March 1, 2000
Last Updated:
May 17, 2001
Report by:
Pranay Kumar Singh, Medical Student (Manchester Royal Infirmary)
Search checked by:
Katrina Richell-Herren, Manchester Royal Infirmary
Three-Part Question:
In [patients with suspected overdose] is [a single dose of flumazenil] indicated to [safely diagnose benzodiazepine ingestion] ?
Clinical Scenario:
An unresponsive young adult is brough to the emergency department. No history is available. Neurological examination reveals no focal abnormality and pupils are mid-size and reactive. Blood glucose is normal. You suspect an overdose and wonder whether flumazenil should be given to ascertain whether benzodiazepines are involved.
Search Strategy:
Medline 1966-01/00 using the OVID interface.
Search Details:
[({exp flumazenil OR flumazenil.mp} AND {exp overdoses OR overdoses.mp OR exp poisoning OR poisoning.mp}) AND {exp diagnosis OR exp diagnosis, differential OR diagnosis.mp OR diagnos$.mp}] LIMIT to human AND english.
Outcome:
45 papers found of which 39 were irrelevant or of insufficient quality. The remaining 6 papers are shown in the table.
Relevant Paper(s):
| Study Title | Patient Group | Study type (level of evidence) | Outcomes | Key results | Study Weaknesses |
|---|---|---|---|---|---|
| The effect of flumazenil (Ro 15-1788) in the management of self-induced benzodiazepine poisoning. A double-blind controlled study. Hojer J and Baehrendtz S. 1988 Sweden. | 52 ICU patients with suspected drug overdose. Flumazenil vs placebo. |
PRCT | Glasgow Coma Scale score | Significantly improved | |
| Side effect rate | No difference | ||||
| Use of flumazenil in intoxicated patients with coma. A double-blind placebo-controlled study in ICU. Ritz R, Zuber M, Elsasser S, Scollo-Lavizzari G. 1990 Switzerland. | 23 ICU patients with suspected drug overdose. Flumazenil vs placebo. |
PRCT | Conscious level | Significant improvement | 7 overdoses were iatrogenic. |
| Side effect rate | No significant side effects | ||||
| Diagnostic utility of flumazenil in coma with suspected poisoning: a double blind, randomised controlled study. Hojer J, Baehrendtz S, Matell G, Gustafsson LL. 1990 Sweden. | 105 unconscious adults in whom a benzodiazepine overdose could not be excluded. Flumazenil vs placebo. |
PRCT | Conscious level | Significant improvement | |
| Blood gas analysis | Significant improvement | ||||
| Side effect rate | No difference | ||||
| Diagnostic and therapeutic utility of flumazenil in comatose patients with drug overdose. Chern TL, Hu SC, Lee CH Deng JF. 1993 Taiwan. | 61 adults with altered mental status in whom a benzodiazepine overdose could not be excluded. | Diagnostic test study | Benzodiazepine OD | Sensitivity 100%<br><br>Specificity 42% | Gold standard (urinary assay for benzodiazepines) only possible in 44 cases. |
| Empiric use of flumazenil in comatose patients: limited applicability of criteria to define low risk. Gueye PN, Hoffman JR, Taboulet P, Vicaut E, Baud FJ. 1996 USA. | 35 adults admitted to ICU with suspected OD. | Retrospective survey. | Full wakening | 7 cases | Retrospective. |
| Partial wakening | 6 cases | ||||
| Seizures | 5 cases | ||||
| Flumazenil in drug overdose: randomized placebo controlled study to assess cost effectiveness. Barnett R, Grace M, Boothe P et al. 1999 Canada. | 43 adults with suspected OD and GCS < 13 (patients with known tricyclic antidepressant overdose were excluded). Flumazenil vs placebo. |
PRCT | Glasgow Coma Scale score | Significantly improved |
Author Commentary:
All the studies are small. Most are PRCTs investigating the use of flumazenil in the management of benzodiazepine overdose. These show that flumazenil improves conscious level in patients who have taken overdoses. Significant adverse reactions occurred including fitting and transient increases in conscious level. The single diagnostic study gives some idea of the clinical utility of the test.
Bottom Line:
The sensitivity of a single dose of flumazenil is high enough to allow failure to respond to be used as a SnNout for benzodiazepine overdose. The specificity is too low to allow it to be used to rule-in. The possibility of mixed overdose is a relative contraindication to using flumazenil.
References:
- Hojer J and Baehrendtz S.. The effect of flumazenil (Ro 15-1788) in the management of self-induced benzodiazepine poisoning. A double-blind controlled study.
- Ritz R, Zuber M, Elsasser S, Scollo-Lavizzari G.. Use of flumazenil in intoxicated patients with coma. A double-blind placebo-controlled study in ICU.
- Hojer J, Baehrendtz S, Matell G, Gustafsson LL.. Diagnostic utility of flumazenil in coma with suspected poisoning: a double blind, randomised controlled study.
- Chern TL, Hu SC, Lee CH Deng JF.. Diagnostic and therapeutic utility of flumazenil in comatose patients with drug overdose.
- Gueye PN, Hoffman JR, Taboulet P, Vicaut E, Baud FJ.. Empiric use of flumazenil in comatose patients: limited applicability of criteria to define low risk.
- Barnett R, Grace M, Boothe P et al.. Flumazenil in drug overdose: randomized placebo controlled study to assess cost effectiveness.