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Three Part Question

In [overdose with tricyclic antidepressants] does [the addition of glucagon to standard treatments] improve [clinical outcome]?

Clinical Scenario

A 27 year old woman attends the emergency department with a suspected amitriptyline overdose. She has a Glasgow Coma Score of 7, is trypsilating, and has a broad complex tachycardia and a blood pressure of 70/30. After intubation and ventilation and sodium bicarbonate she remains tachycardic at 130 although her complexes have narrowed somewhat and her BP is still low at 80/40. You have heard that tricyclic overdoses may respond to glucagon and wonder whether there is any evidence for this.

Search Strategy

Medline 1966-02/03 using the OVID interface.
[(exp antidepressive agents OR exp antidepressive agents, tricyclic OR exp desipramine OR exp amitriptyline OR tricyc$.af OR amitriptyline.af OR amoxapine.af OR clomipramine.af OR doxepin.af OR dothiepin.af OR imipramine.af OR lofepramine.af OR nortriptyline.af OR trimipramine.af) AND (exp glucagon OR glucagon.af)] Limit to human AND English.

Search Outcome

Altogether 31 papers found, 28 failed to answer the 3 part question, the 3 relevant papers are case reports summarised below.

Relevant Paper(s)

Author, date and country	Patient group	Study type (level of evidence)	Outcomes	Key results	Study Weaknesses
Ruddy JM et al, 1972, Australia	4 year old ingested approx 1000mg imipramine, episode of PEA 1.5 hours duration	Case report	Cardiac status	Improved with 1 mg boluses glucagon	Case report Pt also received pyridostigmine, sodium bicarbonate, isoprenaline, digoxin, lignocaine and mannitol
Sener EK et al, 1995, UK	25 year old woman. Plasma toxicology - imipramine 3.0mg/l, desipramine 0.18 mg/l, diazepam 2.9mg/l, nordiazepam 2.2mg/l, chlorpromazine 0.3mg/l, temazepam 0.25mg/l	Case report	Blood pressure	No response to 1mg bolus glucagon. 40mmHG systolic rise after glucagon	Multiple drugs ingested in overdose Pt also received sodium bicarbonate, phenytoin and isoprenaline and fluid resuscitation
			Cardiac rhythm	No response to 1mg bolus glucagon. Broad complex reverted to sinus after 10mg bolus
Sensky PR et al, 1999, UK	36 year old OD-admission toxicology dothiepin 2.58mg/l, desmethyldothiepin 0.51mg/l, paracetamol 135mg/l, diazepam 0.33mg/l, nordiazepam 0.12mg/l	Case report	Blood pressure	No response to 1mg bolus glucagon. 30mmHG systolic rise after glucagon	Case Report Multiple drugs ingested in overdose Pt also received n-acetylcysteine, adrenaline, noradrenaline, ephedrine, dobutamine, and aminophylline with fluid restriction
			Cardiac rhythm	No response to 1mg bolus glucagon. Broad complex reverted to sinus after 10mg bolus

Comment(s)

Although all 3 patients received multiple treatments the authors state the improvement in condition was immediately after high dose glucagon administration. TNo reports of failure to response to glucagon are found in the literature. This is most probably attributable to reporting bias. Further research is required.

Clinical Bottom Line

There is not enough evidence currently available to support the use of glucagon in tricyclic overdose.

References

1. Ruddy JM, Seymour JL, Anderson NG. Management of tricyclic antidepressant ingestion in children with special reference to the use of glucagon. Medical Journal of Australia 1972;1(13):630-3.
2. Sener EK, Gabe S, Henry JA. Response to glucagon in imipramine overdose. Journal of Toxicology - Clinical Toxicology 1995;33(1):51-3.
3. Sensky PR and Olczak SA. High dose intravenous glucagon in severe tricyclic poisoning. Postgraduate Medical Journal 1999;75(888):611-2.