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Three Part Question

In [patients who have taken an overdose of tricyclic antidepressants and develop dysrhythmias] does [magnesium sulphate or standard treatment] lead to [improved rates of cardioversion to sinus rhythm and haemodynamic stability]?

Clinical Scenario

A thirty year-old lady with a history of depression is brought into the Resuscitation Room as a "Standby Call". She claims to have taken 50 of her amitriptyline tablets. Her ECG demonstrates ventricular tachycardia.
You wonder whether magnesium sulphate will confer any advantage over stndard treatment (including correction of hypoxia and acidosis and bicarbonate infusion).

Search Strategy

Ovid MEDLINE 1950 - 2007 February Week 4
Ovid EMBASE 1980 - 2007
Ovid CINAHL 1982 - 2007 March Week 2
Ovid ACP Journal Club 1991 to January/February 2007
Ovid Cochrane Central Register of Controlled Trials (CCRCT) 1st Quarter 2007
Ovid Cochrane Database of Systematic Reviews (CDSR) 1st Quarter 2007
Ovid Database of Abstracts of Reviews of Effects (DARE) 1st Quarter 2007
MEDLINE:
(exp Amitriptyline/ OR exp Nortriptyline/ OR exp Dothiepin/ OR exp Desipramine/ OR exp Clomipramine/ OR exp Doxepin/ OR exp Lofepramine/ OR exp Nortriptyline/ OR exp Trimipramine/ OR exp Imipramine/ OR exp Antidepressive Agents, Tricyclic/ 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 Magnesium/ OR exp Magnesium Sulfate/ OR magnesium.mp.) limit to humans and English language
EMBASE:
(exp Amitriptyline/ OR exp Nortriptyline/ OR exp Dothiepin/ OR exp Desipramine/ OR exp Clomipramine/ OR exp Doxepin/ OR exp Lofepramine/ OR exp Nortriptyline/ OR exp Trimipramine/ OR exp Tricyclic Antidepressant Agent/) 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 Magnesium/ OR exp Magnesium Sulfate/ OR magnesium.mp.) AND (exp Heart Ventricle Tachycardia/ OR Heart Arrhythmia/ OR (arrhythmia$ OR dysrhythmia$).mp.) limit to human and English language
CINAHL:
not lofepramine, trimipramine, tricyclic antidepressant agent
no limits. 4 found, none relevant.
Ovid ACP Journal Club, Cochrane and DARE:
As for Medline (not limited to humans and English language)

Search Outcome

47 papers were found in MEDLINE, 160 in EMBASE, 4 in CINAHL, 1 in ACP Journal Club, 6 in CCRCT, 2 in CDSR and 2 in DARE.
No relevant comparative trials were identified. Two case studies were identified and have been tabulated. An experimental animal study was identified and is discussed.

Relevant Paper(s)

Author, date and country	Patient group	Study type (level of evidence)	Outcomes	Key results	Study Weaknesses
Knudsen and Abrahamsson 1997 Sweden	A 44 year-lady who was admitted after an overdose of amitriptyline. She suffered a cardiac arrest (ventricular fibrillation) after 12 hours.	Case Study	Observed effect of cardiopulmonary resuscitation, sodium bicarbonate, defibrillation (four attempts), lignocaine and epinephrine ("several doses")	Patient remained in ventricular fibrillation	This is only a case study. The observed effects may or may not have been partly due to the effect of magnesium sulphate.
			Observed effect of magnesium sulphate 20mmol x2 and further defibrillation	Spontaneous return of circulation; "Stable regular heart rhythm". Haemodynamic performance normalised.
Citak et al 2002 Turkey	A 23 month-old boy who had taken 36mg/kg of amitriptyline and had been successfully resuscitated from cardiac arrest after 70 minutes. Following return of circulation, he was in ventricular tachycardia.	Case Study	Observed effect of lignocaine, bicarbonate and attempted electrical cardioversion	No effect	Case study. The observed effects may or may not have been partly due to the effects of magnesium sulphate.
			Observed effect of magnesium sulphate	Cardiac rhythm normalised without side-effects.

Comment(s)

There are two reports of the successful use of magnesium sulphate for dysrhythmias associated with tricyclic antidepressant use. The effects have not been scientifically validated. Knudsen and Abrahamsson (1994) reported that magnesium sulphate was superior to lignocaine for the successful cardioversion of amitriptyline-induced ventricular tachycardia in rats. There are no reports of potential adverse effects of magnesium sulphate in this context.

Clinical Bottom Line

It is reasonable to consider the use of magnesium sulphate for refractory dysrhythmias causing haemodynamic instability in the context of tricyclic antidepressant overdose.

Level of Evidence

Level 3 - Small numbers of small studies or great heterogeneity or very different population.

References

1. Knudsen K; Abrahamsson J. Magnesium sulphate in the treatment of ventricular fibrilation in amitriptyline poisoning European Heart Journal 1997; 18: 881-882
2. Ditak A; Soysal DD; Ucsel R; Karabocuolo M; Uzel N. Efficacy of long duration resuscitation and magnesium sulphate treatment in amitriptyline poisoning [Abstr] European Journal of Emergency Medicine 2002; 9(1): 63-66