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Three Part Question

In [an adult with tricyclic antidepressant poisoning] is [intravenous lipid emulsion/Intralipid/Liposyn II] [beneficial in resistant hypotension and refractory arrhythmias]?

Clinical Scenario

A patient with tricyclic antidepressant overdose is treated in the Emergency Department. He is hypotensive and drowsy and has prolonged QTc on electrocardiogram. Blood gas shows metabolic acidosis. He is given intravenous fluids and sodium bicarbonate boluses until his pH becomes 7.6. However, he remains hypotensive. His rhythm then changes to VT. You remember that intravascular lipid emulsion (intralipid) has been used for overdoses of lipid-soluble drugs and you wonder whether it could be effective in this patient.

Search Strategy

MEDLINE 1966 to Week 2 January 2010
EMBASE 1980 to Week 2 January 2010
Google search

[{exp Antidepressive Agents, Tricyclic/ or tricyclic.mp} OR {clomipramine.mp. or exp Clomipramine/ } OR {exp Amitriptyline/ or amitriptyline.mp.} OR {nortryptiline.mp. or exp Nortriptyline/} OR dothiepin.mp. or exp Dothiepin/} OR {imipramine.mp. or exp Imipramine/} OR {doxepin.mp. or exp Doxepin/}] AND [{ intralipid.mp. or exp Fat Emulsions, Intravenous/ } OR {intravenous lipid emulsion.mp. or exp Fat Emulsions, Intravenous/ } OR {exp Fat Emulsions, Intravenous/ or liposyn$.mp.}]

The Cochrane library January 2010: (Intralipid, ti.ab OR lipsyn II.ti.ab,) AND (MeSH descriptor Antidepressive Agents, Tricyclic explode all trees) 0 results.

Search Outcome

Medline: six papers of which none were relevant. EMBASE: 16 papers of which none were relevant. Google: one systematic review and two case reports. The systematic review did not contain relevant human studies/reports. One of the case reports was published as an abstract at the North American Congress of Clinical Toxicology 2009, the other as a case report on the lipid rescue webpage.

Relevant Paper(s)

Author, date and country	Patient group	Study type (level of evidence)	Outcomes	Key results	Study Weaknesses
Carr et al, 2009, Canada	80 year-old man, ingested 1.5gr doxepin	Case report/abstract	Patient found with GCS 3, BP 56/34, HR 60. QRS 113ms. Patient intubated, treated with fluids, NaHCO3, dopamine, norepinephrine, vasopressin. Despite treatment, patient remained hypotensive and QRS widened further.	225ml bolus of 20% Intravascular lipid emulsion, followed by infusion for a total of 100gr over 90 minutes. BP stabilized 2.5 hrs after starting infusion.	1 case only.
Brooks, C, 2009,	53year old female with mixed overdose: amitryptiline, citalopram, fluoxetine,lorazepam and alcohol.	Case report on Lipidrescue website.	Patient arrived in ED with GCS 3, tachycardic, preserved BP, QRS 114ms. Patient intubated.	Intralipid started 3 hours after arrival in hospital. 1.5ml/Kg of 20% intralipid bolus over 1 minute, followed by an infusion of 0.25ml/kg/min for the following 2 hours. QRS duration decreased to 100ms 4 hours after arrival. 48 hour ICU	1 case. Not formally published. Multiple drug ingestion.

Comment(s)

There are no human studies about use of intralipid in tricyclic antidepressant overdose. There is a small study3 in which humans were given therapeutic doses of tricyclic antidepressant and intralipid. In this study, patients treated with intralipid developed a non-significant increase in blood tricyclic level, which would support the hypothesis that intralipid attracts tricyclics away from tissues by creating an expanded lipid compartment. However, the pharmacology for therapeutic and toxic doses of tricyclics is different. The use of intralipid for tricyclic antidepressant overdose has been shown to be effective in four animal studies.4–7 Despite lack of clear evidence, Toxbase advises intralipid when there are life-threatening arrhythmias resistant other standard therapies.9 In the UK, intralipid is also recommended for treatment of severe local anaesthetic toxicity.10

Clinical Bottom Line

There is no clear evidence about the effectiveness of Intralipid in tricyclic antidepressant overdose.

References

1. Carr D, Boone A, Hoffman RS, Martin K, Ahluwalia N. Successful resuscitation of a doxepin overdose using intravenous fat emulsion (IFE). Clinical Toxicology 2009; 47(7): 710.
2. Brooks, C. Case report on Lipid rescue website (accessed 09 Feb 2010).
3. Minton N, Goode A, Henry J. The effect of a lipid suspension on amitryptiline disposition. Arch Toxicol. 1987; 60:467-9.
4. Harvey M, Cave G. Intralipid outperforms sodium bicarbonate in a rabbit model of clomipramine toxicity. Ann Emerg Med 2007; 49(2):178-85.
5. Yoav G, Odelia G, Shaltiel C. A lipid emulsion reduces mortality from clomipramine overdose in rats. Vet Human Toxicol. 2004; 44:30.
6. Bania T, Chu J. Haemodynamic effect of Intralipid in amitryptiline toxicity. Acad Emerg Med. 2006; 13 No 5 (S1): 117, Abstract 438.
7. Harvey M, Cave G. Correlation of plasma and peritoneal dialysate clomipramine concentration with haemodynamic recovery after Intralipid infusion in rabbits. Acad Emer Med 2009; 16:151-6.
8. Cave G, Harvey M. Intravenous lipid emulsion as antidote beyond local anaesthetic toxicity: a systematic review. Acad Emerg Med 2009; 16(9):815.
9. Toxbase. [Online database] www.Toxbase.org (Accessed November 2009).
10. Association of Anaesthetists of Great Britain and Ireland (AAGBI). Guidelines for the management of severe local anaesthetic toxicity. http://www.aagbi.org/publications/guidelines/docs/latoxicity07.pdf 2007