Presentation
The authors reviewed the findings in 165 patients presenting to an ED with antidepressant overdose. [ncbi.nlm.nih.gov]
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]
- 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]
- Hunting
Goldberg RJ, Capone RJ, Hunt JD. Cardiac complications following tricyclic antidepressant overdose: issues for monitoring policy. JAMA 1985; 254: 1772–5 PubMed CrossRef Google Scholar 26. Niemann JT, Bessen HA, Rothstein RJ, et al. [doi.org]
Vohra et al. ( 65 Vohra J, Burrows G, Hunt D, Sloman G. The effect of toxic and therapeutic doses of tricyclic antidepressant drugs on intracardiac conduction. [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]
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]
[…] 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]
- 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]
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]
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]
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]
If the ventricular tachycardia does not respond to the magnesium then a lidocaine infusion at 1.0-1.5 mg/kg up to 3 mg/kg should be given. [ems1.com]
Typical ECG of TCA toxicity demonstrating: •Sinus tachycardia with first-degree AV block (P waves hidden in the T waves, best seen in V1-2). •Broad QRS complexes. •Positive R' wave in aVR. [quizlet.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]
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]
(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]
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]
Amitriptyline Cyclobenzaprine Chemical structure Toxicity: TCA effect Wide complex tachycardia (Na channel blockade) Hypotension (alpha blockade) Seizures (GABA antagonism) Yes No Toxicity: Anticholinergic effect Sedation Tachycardia Hypertension Urinary [aliem.com]
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]
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]
These commonly include dry mouth, blurred vision and constipation. Some patients may experience drowsiness while taking tricyclic antidepressants. [drugs.nmihi.com]
Neurologic
- Seizure
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]
More severe complications include hypotension, cardiac rhythm disturbances, hallucinations, and seizures. [en.wikipedia.org]
Seizures and aspiration pneumonia may occur regardless of initial BP. [ncbi.nlm.nih.gov]
- 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]
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]
Labored breathing, low blood pressure, shock, enlarged pupils, coma, agitation, hallucinations, muscle rigidity, convulsions, and agonal breathing were also reported. [aa400415.wordpress.com]
Initial or mild symptoms typically develop within 2 hours and include tachycardia, drowsiness, a dry mouth, nausea and vomiting, urinary retention, confusion, agitation, and headache. [en.wikipedia.org]
- Confusion
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]
Symptoms may include elevated body temperature, blurred vision, dilated pupils, sleepiness, confusion, seizures, rapid heart rate, and cardiac arrest. [en.wikipedia.org]
[…] 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]
- 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]
[…] 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]
Imipramine and electrocardiographic abnormalities in hyperactive children. Am J Psychiatry 1975 ; 132: 542 – 545 ). [dx.doi.org]
Workup
Serum
- Bicarbonate Increased
Increases amount of drug in non-ionized form and may decrease binding to Na-channels [cite]11482860[/cite] May need many, many amps. [emcrit.org]
Epinephrine and sodium bicarbonate independently and additively increase survival in experimental amitriptyline poisoning. Crit Care Med 1997 ; 25: 669 – 674 [Crossref], [PubMed], [Web of Science ®], [Google Scholar] ). [dx.doi.org]
- Bicarbonate Decreased
Apparently, this somehow "decreases sodium channel blockade by voltage-dependent drug-binding changes ". Beyond the use of bicarbonate itself, the desired alkaline pH can be achieved by hyperventilation. This is very old-school (eg. [derangedphysiology.com]
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]
It commonly causes prolongation of QT interval and Torsade de pointes, tachyarrhythmias or bradyarrhythmias. Tachyarrhythmias are commonly of ventricular origin such as VT or ventricular fibrillation or of supraventricular origin. [bmcresnotes.biomedcentral.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 Oct;25(10):1721-6. PMID: 9377889 Liebelt EL, et al. [lifeinthefastlane.com]
Serial electrocardiogram changes in acute tricyclic antidepressant overdoses. Crit Care Med 1997 ; 25: 1721 – 1726 Peters RW, Buser GA, Kim HJ, Gold MR. Tricyclic overdose causing sustained monomorphic ventricular tachycardia. [dx.doi.org]
Treatment
There is no role for physostigmine in the treatment of tricyclic toxicity as it may increase cardiac toxicity and cause seizures. [en.wikipedia.org]
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]
Seizures Diazepam is the preferred drug treatment. [calsprogram.org]
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
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]
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]
Tricyclic antidepressants are highly protein bound and have a large volume of distribution ; therefore removal of these compounds from the blood with hemodialysis, hemoperfusion or other techniques are unlikely to be of any significant benefit. [12] Epidemiology [ipfs.io]
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]
Administration of 1meq/kg of sodium bicarbonate will bind the medication for excretion to prevent continued or ongoing absorption of the drug. [ems1.com]
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]
To prevent Wernicke encephalopathy aka brain damage Trimipramine (Surmontil) Not to exceed 200mg a day Protriptyline (Vivactil) Not to exceed 60mg a day Wernicke's encephalopathy ... a neurological disorder caused by thiamine deficiency, typically from [quizlet.com]