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Tricyclic Antidepressant Overdose

Poisoning Tricycl Antidepres


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]
  • The authors reviewed the findings in 165 patients presenting to an ED with antidepressant overdose.[ncbi.nlm.nih.gov]
  • Altogether 82 papers were found using the reported search, of which one presented the best evidence to answer the clinical question.[ncbi.nlm.nih.gov]
  • Clinical presentation of overdose from the tricyclic agents includes cardiac arrhythmias, hypotension, seizures, coma and anticholinergic signs such as hyperthermia, flushing and intestinal ileus.[ncbi.nlm.nih.gov]
  • This algorithm correctly predicted which patients required admission, whether due to present or impending complications, and which patients could have been discharged without morbidity or mortality.[ncbi.nlm.nih.gov]
Gastric Lavage
  • Recovery of cyclic depressants with gastric lavage. J Emerg Med 1989 ; 7 : 373 –7.[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]
  • Esophageal perforation: an unusual complication of gastric lavage. Ann Emerg Med 1984; 13: 146 PubMed CrossRef Google Scholar 16. Allan BC. The role of gastric lavage in the treatment of patients suffering from barbiturate overdose.[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]
  • Acta Anaesthesiol Scand 1984 ; 28: 666 – 670 [Crossref] , [PubMed] , [Web of Science ] , [Google Scholar] , 65 Vohra J , Burrows G , Hunt D , Sloman G .[doi.org]
Fever
  • 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]
  • , 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]
  • 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[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]
  • heart failure 31 .[emedexpert.com]
  • The use of imipramine in depressed patients with congestive heart failure . JAMA 1983 ; 250: 1997 – 2001 [Crossref] , [PubMed] , [Web of Science ] , [Google Scholar] ).[doi.org]
Hypothermia
  • 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]
  • 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]
Hypotension
  • The overall frequency of admission hypotension (systolic BP less than 95 mmHg) was 34% (22 of 64 patients).[ncbi.nlm.nih.gov]
  • Class II agents (beta-blockers) may also precipitate hypotension and cardiac arrest.[ncbi.nlm.nih.gov]
  • Her lung injury may have been the result of a variety of factors including hypotension, metabolic acidosis, possible aspiration, or a direct action on the lung parenchyma by desipramine.[ncbi.nlm.nih.gov]
  • Systemic arterial hypotension is a frequent occurrence in major overdoses.[ncbi.nlm.nih.gov]
  • The successful outcome of two cases of TCA overdose complicated by hypotension, unresponsive to an initial treatment with physostigmine fluid challenge and dopamine (greater than 15 micrograms/kg/min) but subsequently responsive to an infusion of norepinephrine[ncbi.nlm.nih.gov]
Tachycardia
  • ECG abnormalities, with the exception of sinus tachycardia and infrequent PVC's were associated with a severely depressed sensorium and disappeared with neurological improvement, usually in 24 h.[ncbi.nlm.nih.gov]
  • Sinus tachycardia with QRS prolongation may be difficult to distinguish from ventricular tachycardia.[ncbi.nlm.nih.gov]
  • The diagnosis must be considered in known or suspected overdoses, and signs such as a dry axilla, tachycardia, and wide QRS must be specifically sought.[ncbi.nlm.nih.gov]
  • A 46-year-old woman presented to the emergency department with coma, hypotension, tachycardia, and a prolonged QRS interval after the ingestion of a large quantity of Elavil.[ncbi.nlm.nih.gov]
  • Patients with the isolated findings of sinus tachycardia or QTc prolongation had no complications.[ncbi.nlm.nih.gov]
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]
  • 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]
  • 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]
Blurred Vision
  • Symptoms may include elevated body temperature, blurred vision, dilated pupils, sleepiness, confusion, seizures, rapid heart rate, and cardiac arrest.[en.wikipedia.org]
  • 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]
  • 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][ipfs.io]
  • […] 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]
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]
  • CONCLUSIONS: Overall, the studies suggested that the ECG and TCA concentration have similar but relatively poor performance for predicting complications, such as seizures, VA or death, associated with TCA overdose.[ncbi.nlm.nih.gov]
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]
  • 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][ipfs.io]
  • […] 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]
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]
  • 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]
  • Labored breathing, low blood pressure, shock, enlarged pupils, coma, agitation, hallucinations, muscle rigidity, convulsions, and agonal breathing were also reported.[aa400415.wordpress.com]
  • GCS was 9 (E2M5V2) although she appeared agitated with bilaterally dilated pupils. There was no external evidence of injury.[icmcasesummaries.com]
  • 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]
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]
  • They found that major manifestations of toxicity on ED evaluation (altered mental status, seizures, arrhythmias, and conduction defects) were commonly associated with a complicated hospital course.[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]
Ataxia
  • […] on the agent 70% excreted by the kidney Acidosis increases the amount of active drug in plasma by decreasing protein binding Clinical effects Cardiovascular Tachycardia Hypotension (cause of mortality) Arrhythmia-SVT/VT VT in 4% of cases approx) CNS Ataxia[emed.ie]
  • […] tachycardia, dilated pupils aka 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[quizlet.com]
  • Clinical manifestations are associated with drowsiness, respiratory depression, dysarthria, and ataxia. Coma is not common but is most often seen in the elderly or patients who have ingested alcohol or other drugs. Treatment is supportive.[academic.oup.com]
  • In a prospective, unblinded trial of imipramine's effects on depression in 44 adults, patients receiving 3.5 mg/kg/day in divided doses (mean 245 mg daily in men and 218 mg daily in women) experienced orthostatic hypotension, dizziness, ataxia, and falls[doi.org]

Workup

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]
Electrocardiogram Change
  • 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]
  • 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]

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]
  • 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.[dx.doi.org]
  • The immediate treatment of arrhythmias involves correcting hypoxia, electrolyte abnormalities, hypotension and acidosis.[dx.doi.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

  • This article reviews epidemiologic, pharmacologic, and therapeutic information to provide a systematic approach to these potentially life-threatening overdoses.[ncbi.nlm.nih.gov]
  • 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]
  • The epidemiology of major depression in South Africa: results from the South African stress and health study. S Afr Med J 2009;99:367-373. 3. Tomlinson M, Grimsrud AT, Stein DJ, Williams DR, Myer L.[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]
Sex distribution
Age distribution

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]
  • […] 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]
  • 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]

Prevention

  • As in other overdoses, counseling to prevent ingestions is more than worth "a pound of the cure."[ncbi.nlm.nih.gov]
  • DISCUSSION: A low-dose infusion of ILE was well tolerated and may have successfully prevented recurrent toxicity in a case of severe tricyclic antidepressant overdose.[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]
  • Immediate measures should be taken in this situation, both to decrease absorption of the culprit drug and to prevent and overcome malignant arrhythmias.[innovationsincrm.com]
  • Do antidepressants prevent suicide? . International Clinical Psychopharmacology, Vol. 21, Issue. 4, p. 211. CrossRef Google Scholar Dean, Angela J. McDermott, Brett M. and Marshall, Robert T. 2006.[doi.org]

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