• 
• 

Three Part Question

[In adults with acute opiate overdose] is [concomitant use of benzodiazepines] associated with a [poorer prognosis in terms of death aspiration, admission to ITU]

Clinical Scenario

A 27 year old man comes into the emergency department with a suspected opiate overdose. He exibits marked miosis and depressed mental status and had needle track marks on his arms. His mother, on questioning, shows you an empty temazepam bottle she found in his pocket. You wonder if he has had a polydrug overdose and if this will result in a poorer outcome.

Search Strategy

Medline 1966 to june week 2 2005 using the ovid interface.
Embase 1980 to 2005 week 26.
CINHAL 1982 to june week 3 2005. 6
[{exp Narcotics AND exp. Overdose AND exp. Benzodiazepines}]

Search Outcome

Medline:Twenty seven papers were found. 4 were relevant.
Embase:15 papers were found. None were relevent to the question.
CINHAL:9 papers were found. None were relevant to the question.
The Cochrane Library: no papers were found.

Relevant Paper(s)

Author, date and country	Patient group	Study type (level of evidence)	Outcomes	Key results	Study Weaknesses
Phillip Oliver and Jenny Keen. Jan 1997 and Dec 2000 UK	Ninety four patients who were judged by the City of Sheffield Coroner to have dies from accidental acute opiate overdose.	Retrospective analysis	Frequency and contribution of other CNS depressants in opiate overdose deaths.	Benzodiazepines in lower quantities are a feature rather than a risk in fatalities, especially in lower quantities.	Drug using profile relied upon friends, family or healthcare professionals information on illicit drug use.Interms of circumstances of death there were contradictory statements from witnesses. The study does not include non fatal overdoses.
Irina Mikolaenko et al. Jan1982- Dec 2000 United States	101 cases of deaths wherein methadone was detected in the blood.	Retrospective review	Frequency of deaths whith co-intoxication with benzodiazepines and concentraion of methadone.	Benzodiazepines were the most frequently detected co intoxicant and have great influence of the variability of methadone concentration.	It is unclear whether intoxication with benzodiazepines is acute or from long term use. Patients with histories of benzodiazepine abuse could have had altered baseline levels of liver enzymes and therefore results would be skewed. Forensic data does not include non- fatal overdoses.
Juan Gutitkrez- Cebollada et al. 1992 Spain	76 heroin addicts admitted to the emergency department; 54 because of overdose and 22 seeking urgent medical care for unrelated causes.	Survey and retrospective review.	Influence of plasma levels of benzodiazepines on GCS.	Plasma concentrations of over 900amg/ml did not significantly influence GCS .	Relatively small sample size. Large difference between sample size of overdose group and non-overdose group. Survey of events surrounding overdose relied on self-report. The benzodiazepines may have affected factors other than the GCS.
Deborah Zador et al. 1992 Australia	Coronial files of 152 heroin related deaths.	Retrospective review.	Influence of blood benzodiazepine levels on morphine levels.	The presence of benzodiazepines does not influence outcome.	Heroin relalted deaths may not have been attributed to overdose but other causes. Subjects were designated into groups according to frequency of use based on accuracy of witnesses.

Comment(s)

These studies have found that co-intoxication with benzodiazepines is does not result in a poorer outcome. This suggests that benzodiazepine use is not implicated in the overdose. However there is evidence to suggest that benzodiazepines potentiate the effects of methadone, with several theories as to why. Despite these findings the belief that benzodiazepine use is a risk factor for overdose in the first place would discourage its use in opiate abusers.

Clinical Bottom Line

The evidence suggests that concomitant use of benzodiazepines does not result in a poorer outcome in opiate overdose.

References

1. Phillip Oliver and Jenny Keen. Concomitant drugs of misuse and drug using behaviours associated with fatal opiate related poisonings in Sheffield, UK, 1997-2000 Addiction 98 pp191-197
2. Irina Mikolaenko et al. A Review of Methadone Deaths in Jefferson County, Alabama. The American Journal of Forensic Medicine and Pathology. 23(3)pp 299-304
3. Juan Gutitkrez- Cebollada et al. Psychotropic drug consumption and other factors associated with heroin overdose. Drug and alcohol Dependence 35 (1994) 169-174
4. Deborah Zador et al. Heroin-related deaths in New South Wales,1992:toxicological findings and circumstances. Medical Journal of Australia. 1996, p 164-204