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Three Part Question

In [patients who have taken an overdose of tricyclic antidepressants and have developed hypotension] does [the administration of normal saline, colloid or no intravenous fluid] lead to [superior success in treating hypotension, quicker resolution of hypotension, fewer arrhythmias and quicker recovery]?

Clinical Scenario

An eighteen year-old lady has ingested 20 of her 75mg amitriptyline tablets and presented to the Emergency Department. Her blood pressure is 80/40.
You consult TOXBASE, which suggests administering intravenous fluids for the hypotension. You wonder if there is any evidence that intravenous fluids are helpful in this situation and whether there is any evidence that colloid is superior to crystalloid.

Search Strategy

All via the Ovid interface:
MEDLINE 1950 - 2007 March Week 1
EMBASE 1980 - 2007 Week 10
CINAHL 1982 - 2007 March Week 2
Cochrane Database of Systematic Reviews (CDSR) <1st Quarter 2007>
ACP Journal Club <1991 to January/February 2007>
Database of Reviews of Effect (DARE) <1st Quarter 2007>
Cochrane Central Register of Controlled Trials (CCRCT) <1st Quarter 2007>
MEDLINE and EMBASE:
(exp Amitriptyline/ OR exp Nortriptyline/ OR exp Dothiepin/ OR exp Desipramine/ OR exp Clopimpramine/ OR exp Doxepin/ OR exp Lofepramine/ OR exp Nortriptyline/ OR exp Trimipramine/ OR exp Imipramine/ OR Antidepressive Agents, Tricyclic/ OR exp Tricyclic Antidepressant Agent/ [EMBASE only] OR (tricyclic$ OR TCA OR amitriptyline OR nortriptyline OR imipramine OR dothiepin OR dosulepin OR desipramine OR clomipramine OR doxepin OR lofepramine OR nortriptyline OR trimipramine).mp.) AND (exp Hypotension/ OR (hypotension OR hypotensive).mp.) AND (exp Infusion/ OR exp Infusion Fluid/ OR exp Colloid/ OR exp Polygeline/ OR exp Gelatin Succinate/ OR exp Sodium Chloride/ OR (infusion OR colloid OR gelofusine OR haemaccel OR saline).mp.) limit to English language
CINAHL, ACP Journal Club, CCRCT, CDSR and DARE:
(exp Amitriptyline/ OR exp Nortriptyline/ OR exp Dothiepin/ OR exp Desipramine/ OR exp Clopimpramine/ OR exp Doxepin/ OR exp Lofepramine/ OR exp Nortriptyline/ OR exp Trimipramine/ OR exp Imipramine/ OR Antidepressive Agents, Tricyclic/ OR exp Tricyclic Antidepressant Agent/ [EMBASE only] OR (tricyclic$ OR TCA OR amitriptyline OR nortriptyline OR imipramine OR dothiepin OR dosulepin OR desipramine OR clomipramine OR doxepin OR lofepramine OR nortriptyline OR trimipramine).mp.) AND (exp Hypotension/ OR (hypotension OR hypotensive).mp.)

Search Outcome

38 papers were identified in MEDLINE, 107 in EMBASE, 18 in CINAHL, 18 in CDSR, 2 in ACP Journal Club, 2 in DARE and 109 in CCRCT. None were relevant to the three-part question.

Relevant Paper(s)

Author, date and country	Patient group	Study type (level of evidence)	Outcomes	Key results	Study Weaknesses

Comment(s)

There is no direct evidence for the use of intravenous fluids to treat hypotension in tricyclic antidepressant overdose. However, the absence of evidence does not equate to evidence of absence. Tricyclic-induced hypotension is likely to result from a combination of myocardial depression and reduced systemic vascular resistance. While intravenous fluids will not counter either of these effects, they may optimise cardiac preload thus improving the chances that a sufficient cardiac output will be achieved. It is unlikely that a cautious fluid bolus will cause harm in this situation. Where concern exists about potential volume overload, invasive haemodynamic monitoring may be prudent. The age-old argument of colloid versus crystalloid cannot be answered even for this well-defined situation. Colloid is believed to remain in the intravascular compartment for longer than crystalloid. Of note, however, there is some evidence that sodium loading may be important in reversing tricyclic antidepressant toxicity (McCabe et al, 1998), which may lead the undecided clinician to favour saline infusion.

Clinical Bottom Line

There is no evidence within the literature that intravenous fluids counter tricyclic-induced hypotension. As there is a sound physiological rationale for their use, they may still be considered as a useful first line treatment.

References

1. McCabe JL; Cobaugh DJ; Menegazzi JJ; Fata J. Experimental tricyclic antidepressant toxicity: A randomized, controlled comparison of hypertonic saline solution, sodium bicarbonate and hyperventilation Annals of Emergency Medicine 1998; 32(3 I): 329-333