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Three Part Question

In [Tricyclic antidepressant overdose] which [ECG abnormalities] are predictive of [seizures and arrythmias]

Clinical Scenario

You are called to the emergency department following the arrival of a 23 year old male electrician who is suspected of ingesting 25 imipramine tablets. You are shown an ECG that was taken shortly after his arrival. You wonder which ECG abnormalities are predictive of complications.

Search Strategy

MEDLINE 1966-April 2007 PubMed Interface
(Antidepressant or tricyclic or amitriptyline or dothiepin or nortriptyline or imipramine or desipramine or protriptyline or clomipramine or doxepin) and (overdose or poisoning or self poisoning or toxic) and (ecg or ekg or electrocardiogram)

Search Outcome

237 studies were found, 1 recent Meta-Analysis and 1 review paper

Relevant Paper(s)

Author, date and country	Patient group	Study type (level of evidence)	Outcomes	Key results	Study Weaknesses
Bailey B et al 2004	Papers identified from Medline and Cochrane register for studies that investigated criteria for prediciting outcomes in TCA overdose. Papers assessed by 2 investigators. Studies included if possible to construct 2x2 table from TCA concentration or ECG abnormalities against clinical outcomes. The following diagnostic tests were evaluated (1)TCA concentration (2)QRS>0.10 seconds (3)QTc>430 ms (4)R/S ratio >0.7 (5)Right axis deviation of 120-270 degrees in the terminal 40ms frontal plane QRS vector	Meta analysis	Number of Studies	941 studies found, 18 studies were included in the review	Some studies excluded due to mixed outcomes
			Pooled Sensitivity & Specificity to predict Death	QRS=0.81 & 0.62; QTc= 0.50 & 0.68; T40= 0.33 & 0.71 respectively
			Pooled Sensitivity & Specificity to predict Seizures	QRS=0.69 & 0.69; T40= 0.50 & 0.72 respectively
			Pooled Sensitivity & Specificity to predict Ventricular Arryhthmias	QRS=0.79 & 0.46; QTc= 0.78 & 0.56;T40= 0.33 & 0.71; R/S ratio= 0.47 & 0.97 respectively
			Positive & Negative Likelihood ratios for Death	QRS= 2.13 & 0.31; QTc= 1.56 & 0.74; T40= 1.14 & 0.94 respectively
			Positive & Negative Likelihood ratios for Seizures	QRS= 3.18 & 0.38; T40= 1.79 & 0.69 respectively
			Positive & Negative Likelihood ratios for Ventricular Arryhthmias	QRS=1.46 and 0.46; QTc= 1.77 & 0.39; T40= 1.14 & 0.94; QTc= 1.77 & 0.39; R/S ratio= 15.7 & 0.55 respectively
Thanacoody HK. Thomas SH. 2005 UK	review of known papers and studies regarding ECG changes in tricyclic overdose. including recent meta analysis and case reports.	Review	authors conclusion	QRS prolongation >100ms and Right axis deviation are the most reproducible predictors	Search strategy not included

Comment(s)

There are many studies and case reports of the ECG patterns seen in TCA overdose. These changes include prolonged QRS, QTc interval, right axis deviation, R/S ratio in lead aVR, Brugada pattern.The presence of any ECG changes suggests significant TCA overdose which may lead to cardiovascular or neurological sequalae. The studies assessing these changes as predictors of seizures and arrythmias are presented in the comprehensive review by Thanacoody et al. Although no search strategy is included I can find no additional useful papers.

Clinical Bottom Line

The most reliable ECG predictors of seizure and arrhythmia are QRS prolongation >100ms and Right axis deviation.

References

1. Bailey B. Buckley NA. Amre DK A meta-analysis of prognostic indicators to predict seizures, arrhythmias or death after tricyclic antidepressant overdose Journal of Toxicology - Clinical Toxicology 2004; 42(6):877-88
2. Thanacoody HK. Thomas SH. Tricyclic antidepressant poisoning : cardiovascular toxicity. Toxicol Rev. 2005;24(3):205-14.