• 
• 

Three Part Question

In [patients who have taken an overdose of tricyclic antidepressants] is [heart rate] a [predictor of death, arrhythmias and seizures]?

Clinical Scenario

A forty year-old homeless man presents to the Emergency Department claiming to have taken ten of his dothiepin tablets two hours ago.

His ECG shows normal QRS duration and normal QRS axis, his blood pressure is 130/85 and he is fully conscious. He therefore appears to be at low risk of complications but his heart rate is 110 beats per minute. You wonder if this is a useful predictor of complications.

Search Strategy

Ovid Medline 1950 - 2008 June Week 1
Ovid Embase 1980 - 2008 Week 24

(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 (exp Overdose/ or exp Poisoning/ or overdose.mp. or exp Drug Overdose/) AND (exp Heart Rate/ OR exp Tachycardia/ OR exp Tachycardia, Sinus/ OR (tachycardi$ or heart rate).mp.) limit to human(s) and English language

Search Outcome

547 papers were identified (439 in Embase and 108 in Medline). 7 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
Caravati et al 1991	ED overdose patients with a positive serum drug screen for TCA and an available 12-lead ECG 65 had signs of major toxicity (coma, seizures, arrhythmias needing treatment, need for intubation or death 41 had only minor signs of toxicity	Retrospective analysis	Heart rate ≥120bpm for prediction of membership to major toxicity group	Odds ratio 2.86 (P<0.05)	Retrospective
Lavoie et al 1990 United States	187 patients who were admitted to ICU with overdose and tested positive for TCA	Retrospective analysis	Heart rate ≥100bpm among patients with seizures	4/6 (67%) had heart rate ≥100bpm	Retrospective Very small numbers with complications Only dichotomous outcome of heart rate ≥100bpm assessed as predictor
			Heart rate ≥100bpm among patients with arrhythmias or death	3/3 (100%) had heart rate ≥100bpm
			Heart rate ≥100bpm among patients without complications	121/178 (67%) had heart rate ≥100bpm
Emerman et al 1986 United States	All 92 patients age ≥17 years who were admitted to Cleveland Metropolitan General Hospital with TCA overdose between 1975 and 1985.	Retrospective analysis	Mean heart rate in patients with and without complications (hypoventilation, loss of protective	102 +/- 20 (no complications) vs. 115 +/- 21 (with complications), P<0.01	Retrospective 38 patients had a mixed drug overdose (although subgroup analysis of patients with pure TCA overdose yielded similar results) Only 92 patients included over a 10 year period.
			Multivariate logistic regression model to predict complications	Only GCS was a significant independent predictor of complications
Foulke et al 1986	165 patients who presented to the ED following antidepressant overdose	Retrospective analysis	Patients with isolated finding of sinus tachycardia	No complications	Retrospective
Yanagawa et al 2007 Japan	175 patients who were intubated following psychotropic drug overdose between January 2000 and December 2005 Patients were divided into an “early group” (extubated within 2 days) and a late group (not extubated within 2 days)	Retrospective analysis	Mean heart rate (SE) in early and late groups	92.6 +/- 1.9 (early group) vs. 107 +/- 4.1 (late group), P=0.001	Retrospective Significant selection bias: only intubated patients included No analysis of different GCS cut-offs for prediction of late extubation
			Multivariate logistic regression model to identify independent predictors of late extubation	Heart rate was an independent predictor (OR 1.02, 95% CI 1.00-1.03, P=0.01)

Comment(s)

Sinus tachycardia is a common finding in patients with TCA overdose, with studies quoting figures from 40.7% to 88% (Rudorfer 1919;Unverir R et al. 2006). Further, tabulated data suggest that the absence of tachycardia does not preclude the occurrence of serious complications. On multivariate analysis only Yanagawa et al (Yanagawa Y, Sakamoto T, & Okada Y 2007) found that heart rate was an independent predictor of adverse outcome (late extubation among intubated patients). However a series of retrospective analyses have found that increased heart rate is associated with an increased risk of complications following TCA overdose, including death, arrhythmias, seizures, coma and hypotension. Petit et al found that patients with higher serum TCA levels were significantly more likely to have a heart rate >120bpm (P<0.01)(Petit et al. 1977). Caravati et al found that a heart rate ≥120bpm carried an odds ratio of 2.86 for the prediction of complications. While other clinical findings (including Glasgow Coma Scale and QRS duration) appear to be stronger predictors of complications than heart rate and should be used preferentially to identify high risk patients and to guide therapy, patients with significant sinus tachycardia should be carefully monitored for the occurrence of complications. Given the potential risk of arrhythmias this should include ECG monitoring.

Clinical Bottom Line

Heart rate appears to be a significant predictor of complications following TCA overdose, although it has questionable additive value when other clinical findings (including Glasgow Coma Scale and QRS duration) are taken into account.

Level of Evidence

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

References

1. Buckley,Nicholas; Chevalier,Stephan; Leditschke,I.Anne; O''Connell,Dianne; Leitch,James; Pond,Susan The limited utility of electrocardiography variables used to predict arrhythmia in psychotropic drug overdose Critical Care 2003; 7: 101-107
2. Caravati EM, Bossart PJ Demographic and electrocardiographic factors associated with severe tricyclic antidepressant toxicity J Toxicol Clin Toxicol 1991; 29:31-43.
3. Lavoie FW, Gansert GG, Weiss RE Value of initial ECG findings and plasma drug levels in cyclic antidepressant overdose Annals of Emergency Medicine 1991;(6):696-700
4. Emerman CL, Connors AF, Burma GM Level of consciousness as a predictor of complications following tricyclic overdose Annals of Emergency Medicine 1987; 16:326-330
5. Foulke GE, Albertson TE, Walby WF Tricyclic antidepressant overdose: emergency department findings as predictors of clinical course Am J Emerg Med 1986; 4:496-500
6. Yanagawa Y, Sakamoto T, Okada Y Recovery from a psychotropic drug overdose tends to depend on the time from ingestion to arrival, the Glasgow Coma Scale, and a sign of circulatory insufficiency on arrival American Journal of Emergency Medicine 2007; 25:757-761.
7. Petit JM, Spiker DG, Ruwitch JF, Ziegler VE, Weiss AN, Biggs JT. Tricyclic antidepressant plasma levels and adverse effects after overdose. Clinical Pharmacology & Therapeutics 21(1):47-51, 1977
8. Unverir R, Atilla R, Karcioglu O, Topacoglu H, Demiral Y, Tuncok Y A retrospective analysis fo antidepressant poisonings in the Emergency Department: 11-year experience uman & Experimental Toxicology 2006;25:605-12.
9. Rudorfer MV Cardiovascular changes and plasma drug levels after amitriptyline overdose Journal of Toxicology - Clinical Toxicology 1991;(1):67-78