Presentation
This guideline presents a summary of the best available evidence to guide the management of adult patients who present to the ED following an overdose of tricyclic antidepressant agents (TCA). [ncbi.nlm.nih.gov]
These patients often present with fits, coma, and cardiac arrhythmias. Death from cardiac arrest may also occur. Symptoms usually appear within 30 to 60 minutes of ingestion, and reach their peak intensity within 4 to 12 hours. [gpnotebook.co.uk]
Entire Body System
- Gastric Lavage
Recovery of cyclic depressants with gastric lavage. J Emerg Med 1989 ; 7 : 373 –7. [dx.doi.org]
In view of the paucity of evidence that gastric lavage removes a significant amount of drug and the risk of complications associated with the procedure, the routine use of gastric lavage in the management of patients with TCA poisoning is not appropriate [ncbi.nlm.nih.gov]
- Enuresis
There is, however, little evidence for an analgesic effect in acute pain. [4] Nocturnal enuresis Tricyclics with greater anti-muscarinic action (i.e., amitriptyline, imipramine and nortriptyline ) may prove useful in helping to treat nocturnal enuresis [wikidoc.org]
[…] utilized for the treatment of several other psychiatric conditions, including obsessive-compulsive disorder, attention-deficit disorder, and anxiety disorders, and medical problems, such as chronic pain syndromes, peripheral neuropathies, nocturnal enuresis [innovationsincrm.com]
These drugs may also be used to treat other conditions, such as bedwetting ( enuresis ), obsessive-compulsive disorder (OCD) and some chronic pain conditions. [drugs.nmihi.com]
A normal dose of imipramine for treatment of enuresis is 1.5 mg/kg/day. As there is limited toxicity data in children, refer patients ingesting > 1.5 mg/kg into the ED. [calsprogram.org]
Childhood enuresis. II. Psychopathology, tricyclic concentration in plasma, and antienuretic effect. [dx.doi.org]
- Fever
sudden high fever with jaundice, priapism (condition marked by persistent erections), swollen lymph nodes and respiratory distress. [drugs.nmihi.com]
A tricyclic overdose may cause: Hallucinations Drowsiness Enlarged pupils Fever Irregular heartbeat Severe dizziness Severe muscle stiffness or weakness Restlessness or agitation Breathing problems, respiratory failure Vomiting Convulsions Coma A TCA [healthyplace.com]
[…] small pupils Hypothermia, bradycardia, respiratory arrest, acute lung injury Airway protection, IPPV naloxone Salicylates Aspirin Altered mental status, respiratory alkalosis, metabolic acidosis, tinnitus, hyperpnoea, tachycardia, sweating Low-grade fever [academic.oup.com]
Arrhythmias, including VF and torsade Central nervous system features Drowsiness Coma Seizures Pyramidal signs and rigidity Ophthalmoplegia Anticholinergic features Dry mouth Blurred vision Dilated pupils Urinary retention Ileus, absent bowel sounds High fever [derangedphysiology.com]
Generally anticholinergic effects do not cause serious clinical problems but cases of toxic megacolon and intestinal perforation have been described. 11, 12 By impairing sweating heat dissipation is reduced and this can result in a fever, especially if [dx.doi.org]
- Congestive Heart Failure
In patients who can not tolerate the volume of fluid associated with an infusion (eg, those with congestive heart failure, renal impairment, or end-stage renal disease), use of repeated boluses may be preferable. [emedicine.medscape.com]
The use of imipramine in depressed patients with congestive heart failure. JAMA 1983 ; 250: 1997 – 2001 [Crossref], [PubMed], [Web of Science ®], [Google Scholar] ). [dx.doi.org]
- Hypothermia
Successful use of therapeutic hypothermia after cardiac arrest due to amitryptiline and venelafaxine intoxication. Ther hypothermia Temp manag. 2015;5(2):104–9. View Article PubMed Google Scholar Eken C. [bmcresnotes.biomedcentral.com]
defaecation, muscle weakness, bronchorrhoea Bradycardia, dilated or constricted pupils, seizures, respiratory failure, paralysis Airway protection and IPPV, atropine, pralidoxime Opioid Heroin, morphine CNS and respiratory depression, small pupils Hypothermia [academic.oup.com]
Hypertension followed by hypotension RESP: ARDS, aspiration pneumonitis CNS: Seizures, CNS depression, drowsiness, coma, extra pyramidal effects GI/GU: Decreased or absent bowel sounds, urinary retention OTHER: Metabolic acidosis, hyper-/hypothermia Decontamination [calsprogram.org]
Respiratoric
- Aspiration
Seizures and aspiration pneumonia may occur regardless of initial BP. [ncbi.nlm.nih.gov]
Fatal pulmonary aspiration of oral activated charcoal. BMJ 1988; 297: 459–60 PubMed CrossRef Google Scholar 39. Harris CR, Filandrinos D. Accidental administration of activated charcoal into the lung: aspiration by proxy. [doi.org]
Gastrointestinal
- Muscle Rigidity
Labored breathing, low blood pressure, shock, enlarged pupils, coma, agitation, hallucinations, muscle rigidity, convulsions, and agonal breathing were also reported. [aa400415.wordpress.com]
Cardiovascular
- Hypotension
The overall frequency of admission hypotension (systolic BP less than 95 mmHg) was 34% (22 of 64 patients). [ncbi.nlm.nih.gov]
K+ Channel Blockade QTC Prolongation NE & Serotonin Reuptake Inhibition Initial hypertension quickly followed by hypotension Na+ Channel Blockade QRS Prolongation Hypotension — depresses myocardial contractility Ventricular dysrhythmias Brugada-like findings [em3.org.uk]
- Tachycardia
Sinus tachycardia with QRS prolongation may be difficult to distinguish from ventricular tachycardia. [ncbi.nlm.nih.gov]
Sinus tachycardia is the most common manifestation seen, other ECG changes, which are seen are premature ventricular contractions, ventricular tachycardia and fibrillation, supraventricular tachycardia with aberrancy, sinus arrest, idioventricular rhythm [mjdrdypu.org]
There is marked QRS widening with tachycardia and a positive R’ wave in aVR. Example 3 Flecainide overdose Similar ECG changes are seen with other sodium-channel blocking agents. [lifeinthefastlane.com]
- Hypertension
K+ Channel Blockade QTC Prolongation NE & Serotonin Reuptake Inhibition Initial hypertension quickly followed by hypotension Na+ Channel Blockade QRS Prolongation Hypotension — depresses myocardial contractility Ventricular dysrhythmias Brugada-like findings [em3.org.uk]
(J Emerg Med 1995;13(6):781-5) This one is from Bryan Hayes) Pharmacologic Effects of TCAs K+ Channel Blockade QTC Prolongation NE & Serotonin Reuptake Inhibition Initial hypertension quickly followed by hypotension Na+ Channel Blockade QRS Prolongation [emcrit.org]
Amphetamine, Methamphetamine, Cocaine, Diet aids, Nasal decongestants, Bath Salts Stimulant Signs and symptoms Restlessness, Agitation, Incessant talking, insomnia, Anorexia, dilated pupils, tachycardia, tachypnea, hypertension or hypotension, paranoia [quizlet.com]
It can rarely cause ventricular dysrhythmias and hypertension and drowsiness at very high doses. Tricyclic antidepressants Tricyclic antidepressants cause 250 fatalities each year in the UK. [academic.oup.com]
Vasodilators are first-line therapy for treating amphetamine-induced hypertension E. Wide-complex tachydysrhythmias should be treated initially with sodium bicarbonate Question 2. [foamcast.org]
Eyes
- Blurred Vision
Symptoms may include elevated body temperature, blurred vision, dilated pupils, sleepiness, confusion, seizures, rapid heart rate, and cardiac arrest. [en.wikipedia.org]
[…] gastrointestinal distress, diarrhea, respiratory depression, apnea, seizures, coma Anticholinergic Drug Examples Atropine, Scopolamine, Antihistamines, Antipsychotics, Anticholinergic Signs and Symptoms Dry, Flushed skin, hyperthermia, dilated pupils, blurred [quizlet.com]
These commonly include dry mouth, blurred vision and constipation. Some patients may experience drowsiness while taking tricyclic antidepressants. [drugs.nmihi.com]
Clinical Effects HEENT: Nystagmus, blurred vision, dry mouth, flushing, mydriasis CV: Widening of the QRS interval is the most commonly used marker of toxicity. A QRS interval > 0.1 second is indicative of potential toxicity. [calsprogram.org]
vision Dilated pupils Urinary retention Ileus, absent bowel sounds High fever, or inability to regulate temperature Anhidrosis Delirium Metabolic features Metabolic acidosis Respiratory acidosis Management of tricyclic overdose Decontamination Activated [derangedphysiology.com]
Urogenital
- Nocturnal Enuresis
There is, however, little evidence for an analgesic effect in acute pain. [4] Nocturnal enuresis Tricyclics with greater anti-muscarinic action (i.e., amitriptyline, imipramine and nortriptyline ) may prove useful in helping to treat nocturnal enuresis [wikidoc.org]
enuresis, and migraine headaches. [innovationsincrm.com]
Neurologic
- Seizure
Avoid antiarrhythmics Control seizures with IV Lorazepam Consider RSI with Thiopentone (with anaesthetic back up) for status epilepticus. [emed.ie]
Seizures and aspiration pneumonia may occur regardless of initial BP. [ncbi.nlm.nih.gov]
No seizures or ventricular arrhythmias occurred in Group A. In Group B there was a 34 per cent incidence of seizures and a 14 per cent incidence of ventricular arrhythmias. All patients survived. [doi.org]
- Confusion
Symptoms may include elevated body temperature, blurred vision, dilated pupils, sleepiness, confusion, seizures, rapid heart rate, and cardiac arrest. [en.wikipedia.org]
The patient started with a confused mental state and decreased to a GCS of eight, potentially indicating the need for an advanced airway. [ems1.com]
[…] mydriasis agitation and seizures, hyperthermia Sedative/hypnotics Drug Examples Phenobarbital, diazepam AKA Valium, thiopental, midazolam aka versed, lorazepam Sedative/hypnotics Signs and symptoms Drowsiness, disinhibition, ataxia, slurred speech, mental confusion [quizlet.com]
In addition to cardiotoxicity and potential QRS prolongation, TCA overdose can cause anticholinergic effects (e.g., flushing, dry mouth, dilated pupils, and hyperpyrexia) and central nervous system (CNS) effects (e.g., confusion and hallucinations). [clinicaladvisor.com]
Symptoms may include elevated body temperature, blurred vision, dilated pupils, sleepiness, confusion, seizures, rapid heart rate, and cardiac arrest. [1] If symptoms have not occurred within six hours of exposure they are unlikely to occur. [2] TCA overdose [ipfs.io]
- Agitation
Cardiovascular Tachycardia Hypotension (cause of mortality) Arrhythmia-SVT/VT VT in 4% of cases approx) CNS Ataxia Nystagmus Sedation, coma Seizures (about 5% of cases) Amblyopia Anticholinergic Mydriasis Dry mouth Absent bowel sounds Urinary retention Agitation [emed.ie]
Amphetamine, Methamphetamine, Cocaine, Diet aids, Nasal decongestants, Bath Salts Stimulant Signs and symptoms Restlessness, Agitation, Incessant talking, insomnia, Anorexia, dilated pupils, tachycardia, tachypnea, hypertension or hypotension, paranoia [quizlet.com]
Nausea, vomiting, agitation, tremor, nystagmus, drowsiness, dysrhythmias, and mild hypertension are the most common features of overdose. Convulsions have been reported up to 10 h post-ingestion. [academic.oup.com]
Labored breathing, low blood pressure, shock, enlarged pupils, coma, agitation, hallucinations, muscle rigidity, convulsions, and agonal breathing were also reported. [aa400415.wordpress.com]
He is agitated and combative, but there is no evidence of traumatic injury. His pupils are dilated, and he is diaphoretic. Which of the following statements is true regarding the treatment of amphetamine and cocaine toxicity? A. [foamcast.org]
- Altered Mental Status
The authors describe a patient with tricyclic antidepressant overdose who presented with altered mental status and whose serial ECG changes played a significant role in diagnosing and predicting the impending cardiovascular toxicity. [ncbi.nlm.nih.gov]
Serotonin syndrome consists of a triad of altered mental status, neuromuscular hyperactivity, and autonomic instability, similar in presentation to neuroleptic malignant syndrome—hyperpyrexia, acidosis, arrythmias, and rhabdomyolysis are seen. [academic.oup.com]
A 24-year-old man presents to the ED via the police because of altered mental status and violent behavior. The patient reportedly had been on a drug binge, using amphetamines and cocaine for the last 2 days. [foamcast.org]
- Hyperactivity
"Attention-deficit/hyperactivity disorder (ADHD) as a noradrenergic disorder". Biol Psychiatry. 46 (9): 1234–42. doi : 10.1016/S0006-3223(99)00192-4. PMID 10560028. ↑ Popper C (1997). [wikidoc.org]
Imipramine and electrocardiographic abnormalities in hyperactive children. Am J Psychiatry 1975 ; 132: 542 – 545 ). [dx.doi.org]
[…] clinical use. [1] Despite the increasing popularity of the selective serotonin reuptake inhibitors (SSRIs) in the treatment of depression, CAs continue to play an important role in the treatment of enuresis, obsessive-compulsive disorder, attention deficit hyperactivity [emedicine.medscape.com]
Workup
QRS Wave
- Wide QRS Complex
In those who have a wide QRS complex (> 100 ms) sodium bicarbonate is recommended. If seizures occur benzodiazepines should be given. In those with low blood pressure intravenous fluids and norepinephrine may be used. [en.wikipedia.org]
In those who have a wide QRS complex ( > 100 ms ) sodium bicarbonate is recommended. [ipfs.io]
There are wide QRS complexes with rapid ventricular rate ( Ventricular tachcardia ): Toxicity Tricyclics have a narrow therapeutic index, i.e. the therapeutic dose is close to the toxic dose. [wikidoc.org]
Rhythm
- Torsades De Pointes
Torsade de pointes occurs uncommonly. Hypotension results from a combination of reduced myocardial contractility and reduced systemic vascular resistance due to alpha-adrenergic blockade. [ncbi.nlm.nih.gov]
Doxepin-induced torsade de pointes tachycardia. Ann Intern Med 2001; 135: 384–5 PubMed Google Scholar 43. Davison ET. Amitriptyline-induced torsade de pointes: successful therapy with atrial pacing. [doi.org]
There may also be a ventricular arrythmia, particularly polymorphic ventricular tachycardia, specifically Torsades de Pointes. This should be treated typically with a magnesium sulfate infusion of 2 g over two minutes. [ems1.com]
Other ECG Findings
- Electrocardiogram Change
Electrocardiogram changes are common and precede the development of hypotension and neurological deterioration, therefore close watch on ECG monitoring is strongly recommended in the patients of TCAs poisoning. References 1. [mjdrdypu.org]
Serial electrocardiogram changes in acute tricyclic antidepressant overdoses. Crit Care Med 1997; 25: 1721–6 PubMed CrossRef Google Scholar 36. Shannon MW. Duration of QRS disturbances after severe tricyclic antidepressant intoxication. [doi.org]
Serial electrocardiogram changes in acute tricyclic antidepressant overdoses. Crit Care Med 1997; 25: 1721–6 PubMed CrossRef Google Scholar 11. Shannon MW. Duration of QRS disturbances after severe tricyclic antidepressant intoxication. [dx.doi.org]
Treatment
We are currently unable to explain the exact mechanism of this treatment but it could have a place in the treatment of severe tricyclic poisoning with hemodynamic instability in addition to the conventional treatment. [ncbi.nlm.nih.gov]
Treatment of antidepressant poisoning with resin hemoperfusion. Hum Toxicol 1982; 1: 361–71 PubMed CrossRef Google Scholar 65. Diaz-Buxo JA, Farmer CD, Chandler JT. Hemoperfusion in the treatment of amitriptyline intoxication. [doi.org]
In patients with dysrhythmias following TCAD overdose, treatment should include alkalinisation to a pH of 7.55 [BestBets] Use 50 - 100 mmol of Sodium Bicarbonate ( 50 - 100 mls of 8.4% Na Bic) as "IV push" Aim for pH of 7.45-7.5. Consider infusion. [emed.ie]
Prognosis
Prognosis GCS of less than 8 predicts serious complications with a sensitivity of 86% and specificity of 89%. A high GCS does not rule out significant ingestion 24. [slideshare.net]
Etiology
We reviewed literature pertaining to the etiology, epidemiology, pathophysiology, and management of TCA-induced lung injury, as well as other case reports. [ncbi.nlm.nih.gov]
Epidemiology
This article reviews epidemiologic, pharmacologic, and therapeutic information to provide a systematic approach to these potentially life-threatening overdoses. [ncbi.nlm.nih.gov]
Tricyclic antidepressants intoxication in Tehran, Iran: epidemiology and associated factors. Hum Exp Toxicol 2011;30:283-288. [http://dx.doi.org/10.1177/0960327110371701] 6. [samj.org.za]
The epidemiology of poisoning. Medicine, Vol. 35, Issue. 10, p. 537. CrossRef Google Scholar Çaksen, Hüseyin Akbayram, Sinan Odabaş, Dursun Özbek, Hanefi Erol, Mehmet Akgün, Cihangir Tuncer, Oguz and Yilmaz, Cahide 2006. [doi.org]
Pathophysiology
We reviewed literature pertaining to the etiology, epidemiology, pathophysiology, and management of TCA-induced lung injury, as well as other case reports. [ncbi.nlm.nih.gov]
Olson K, Benowitz NL (1984) Environmental and drug-induced hyperthermia: pathophysiology, recognition and management. Emerg Med Clin North Am 2: 459–474 Google Scholar 8. [link.springer.com]
Pharmacology/Pathophysiology Tricyclic antidepressants (TCAs) exert their effects by a variety of mechanisms. [calsprogram.org]
Neuromuscular blockade also can be used along with continuous EEG monitoring for the treatment of refractory seizure to avert life-threatening hyperthermia. 2 Understanding the pathophysiology of TCA overdose and its effect on the cardiovascular system [journals.lww.com]
[…] toxic dose. [7] Factors that increase the risk of toxicity include advancing age, cardiac status, and concomitant use of other drugs. [8] However, serum drug levels are not useful for evaluating risk of arrhythmia or seizure in tricyclic overdose. [9] Pathophysiology [ipfs.io]
Prevention
As in other overdoses, counseling to prevent ingestions is more than worth "a pound of the cure." [ncbi.nlm.nih.gov]
These unwanted effects tend to disappear over time in children who take tricyclic antidepressants to prevent bedwetting. Antidepressants must be used with great caution in children, as the U.S. [drugs.nmihi.com]
Administration of 1meq/kg of sodium bicarbonate will bind the medication for excretion to prevent continued or ongoing absorption of the drug. [ems1.com]