ECG vs Serum drug level in Tricyclic antidepressant Overdose

Report By: Fawad Azam - Medical student
Search checked by Tom Bartram - Middle Grade A+E
Institution: MRI
Date Submitted: 12th July 2005
Last Modified: 26th April 2007
Status: Blue (submitted but not checked)

Three Part Question

In [Tricyclic antidepressant overdose] is the [ECG a greater predictor than serum drug level] at predicting [seizures and arrythmias]

Clinical Scenario

A 33 year old woman arrives to the emeregency department with suspected tricyclic antidepressant overdose. Blood samples and an ECG are taken. You wonder whether the ECG or the serum drug level is better at prediciting arryhthmias and seizures.

Search Strategy

MEDLINE 1966-June Week 4 2005 OVID Interface
EMBASE 1980 to 2005 Week 27 OVID Interface
Medline:[{exp ANTIDEPRESSIVE AGENTS, TRICYCLIC OR tricyclic.mp. OR amitriptyline.mp. OR exp AMITRIPTYLINE OR desipramine.mp. OR exp DESIPRAMINE OR clomipramine.mp. OR exp CLOMIPRAMINE OR doxepin.mp. OR exp DOXEPIN OR dothiepin.mp. OR exp DOTHIEPIN OR imipramine.mp. OR exp IMIPRAMINE OR lofepramine.mp. OR exp LOFEPRAMINE OR nortriptyline.mp. OR exp NORTRIPTYLINE OR trimipramine.mp. OR exp TRIMIPRAMINE} AND {overdose.mp. OR exp OVERDOSE OR exp POISONING} AND {ecg.mp. OR exp Electrocardiography OR electrocardiogram.mp OR EKG.mp} LIMIT to English Language and Humans]
EMBASE:[{exp ANTIDEPRESSIVE AGENTS, TRICYCLIC OR tricyclic.mp. OR amitriptyline.mp. OR exp AMITRIPTYLINE OR desipramine.mp. OR exp DESIPRAMINE OR clomipramine.mp. OR exp CLOMIPRAMINE OR doxepin.mp. OR exp DOXEPIN OR dothiepin.mp. OR exp DOTHIEPIN OR imipramine.mp. OR exp IMIPRAMINE OR lofepramine.mp. OR exp LOFEPRAMINE OR nortriptyline.mp. OR exp NORTRIPTYLINE OR trimipramine.mp. OR exp TRIMIPRAMINE} AND {overdose.mp. OR exp OVERDOSE OR exp POISONING} AND {ecg.mp. OR exp Electrocardiography OR electrocardiogram.mp OR EKG.mp} LIMIT to English Language and Humans]

Search Outcome

Medline: 122 studies were found, 1 recent Meta-Analysis found, no papers after this date were relevant to the three part question.
Embase: No additional relevant papers found

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 (T40)	Meta analysis	Number Studies	941 studies found, 18 studies were included in the review	all but one studies retrospective, most non blinded, time between ingestion and measurement not reported
			Pooled Sensitivity & Specificity to predict Death	QRS=0.81 & 0.62; TCA conc= 0.76 & 0.60; QTc= 0.50 & 0.68; T40= 0.33 & 0.71 respectively
			Pooled Sensitivity & Specificity to predict Seizures	QRS=0.69 & 0.69; TCA conc= 0.75 & 0.72; T40= 0.50 & 0.72 respectively
			Pooled Sensitivity & Specificity to predict Ventricular Arryhthmias	QRS=0.79 & 0.46; TCA conc= 0.78 & 0.57; 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; TCA conc= 1.90 & 0.57; QTc= 1.56 & 0.74; T40= 1.14 & 0.94 respectively
			Positive & Negative Likelihood ratios for Seizures	QRS= 3.18 & 0.38; TCA conc= 2.39 & 0.46; T40= 1.79 & 0.69 respectively
			Positive & Negative Likelihood ratios for Ventricular Arryhthmias	QRS=1.46 and 0.46; TCA conc= 1.81 & 0.39; QTc= 1.77 & 0.39; T40= 1.14 & 0.94; QTc= 1.77 & 0.39; R/S ratio= 15.7 & 0.55 respectively

Comment(s)

This study compares the best known ECG markers with serum levels and finds no significant difference between the modalities. A recent review by Thanacoody et al reported that serum TCA concentrations are not reliable predictors of toxicity. Serum measurement is not widely available and can take a lengthy time to complete. ECG monitoring is rapidly available and is at least as good as serum levels at predicting complications. The time after ingestion when an ECG is recorded must also be considered, but can be repeated serially as required.

Clinical Bottom Line

ECG is recommended over serum drug level to predict seizure and arrhythmia.

References

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