Tricyclic Antidepressant Toxicity
OVERVIEW
Tricyclic Antidepressants (TCA) are weak bases (pKa 8.5) that can cause life-threatening sodium channel toxicity leading to:
- anticholinergic effects
- inhibition of catecholamine reuptake (initial increase in sympathetic tone -> prolonged decrease)
- profound alpha-adrenergic blockade
- sodium channel blockade -> cardiotoxicity and CNS effects
HISTORY
- having taken a large quantity of TCA (patients may be asymptomatic for 2-3 hours post ingestion)
- will develop signs of major toxicity within 6 hours
– > 10mg/kg potentially life threatening
– > 30mg/kg will develop pH dependent toxicity + coma for more than 24 hours
EXAMINATION
- CVS – dry mucous membranes, tachycardia, hypertension -> hypotension -> cardiovascular collapse (arrhythmia), postural hypotension, dehydration
- CNS – nystagmus, dizziness, agitation, decreases level of consciousness, unconscious/coma, seizures, increase in tone, clonus, tremor, hypereflexia, pupillary dilation, blurred vision
- GI – N+V, abdominal pain, dry mouth, ileus
- METABOLIC – severe metabolic acidosis, fever
- GU – urinary retention
- SKIN – flushed
- anticholinergic: “blind as a bat, red as a beet, hot as a hare, dry as a bone, mad as a hatter”
INVESTIGATIONS
- ABG – metabolic acidosis
- ECG:
-> sinus tachycardia
-> PR prolongation
-> RAD
-> R wave > 3mm in aVR
-> prolonged QT interval (>430ms)
-> QRS prolongation (>100ms)
-> VF/VT/asystole
-> 2nd or 3rd HB
-> RBBB - Bloods – renal impairment
MANAGEMENT
Resuscitation
- supportive care of airway, breathing and circulation
- a number of anti-arrhythmics are contra-indicated as they prolong depolarisation -> use lignocaine, phenytoin, Mg2+, hypertonic saline.
- often need PAC
- volume resuscitation
- treat seizures with benziodiazepines (ist line), barbiturates (2nd line), other options include: propofol
Electrolyte and Acid-base Abnormalities
- IV NaHCO3 + hyperventilation to ensure pH is >7.5
How NaHCO3 works:
- TCA are weak bases
- increasing the serum pH with bicarbonate -> increases the proportion of non-ionised drug which -> increase in drug distribution throughout rest of body and away from heart
- increased Na+ also overcomes the Na+ receptor blockade
- alkalinsation also accelerates the recovery of Na+ channels by neutralising the protonation of the drug receptor complex
Specific Treatment
- see above
Underlying Cause
- prevent absorption: gastric lavage and charcoal if presents within 1 hour,
- enhanced elimination: haemodialysis not recommended in TCA OD c/o small amount of free drug in plasma
References and Links
CCC Toxicology Series
General
Approach to acute poisoning, ECGs in Tox, Evidenced-based Tox, Toxicology literature summaries, Does anti-venom work?
Toxins / Overdose
Amphetamines, Barbituates, Benzylpiperazine, Beta Blockers, Calcium Channel Blocker, Carbamazepine, Carbon Monoxide, Ciguatera, Citrate, Clenbuterol, Cocaine, Corrosive ingestion, Cyanide, Digoxin, Ethanol, Ethylene Glycol, Iron, Isoniazid, Lithium, Local anaesthetic, Methanol, Monoamine oxidase inhibitor (MAOI), Mushrooms (non-hallucinogenic), Opioids, Organophosphate, Paracetamol, Paraquat, Plants, Polonium, Salicylate, Scombroid, Sodium channel blockers, Sodium valproate, Theophylline, Toxic alcohols, Tricyclic antidepressants (TCA)
Envenomation
Marine, Snakebite, Spider, Tick paralysis
Syndromes
Alcohol withdrawal, Anticholinergic syndrome, Cholinergic syndrome, Drug withdrawals in ICU, Hyperthermia associated toxidromes, Malignant hyperthermia (MH), Neuroleptic malignant syndrome (NMS), Opioid withdrawal, Propofol Infusion Syndrome (PrIS) Sedative toxidrome, Serotonin syndrome, Sympatholytic toxidrome, Sympathomimetic toxidrome
Decontamination
Activated Charcoal, Gastric lavage, GI Decontamination
Enhanced Elimination
Enhanced elimination, Hyperbaric therapy for CO
Antidotes
Antidote summary, Digibind, Glucagon, Flumazenil, HIET – High dose euglycaemic therapy, Intralipid, Methylene Blue, N-Acetylcysteine (NAC), Naloxone
Miscellaneous
Cocaine chest pain, Digoxin and stone heart theory, Hyperbaric oxygen, Hypoxaemia in tox, Liver failure in tox, Liver transplant for paracetamol, Methaemoglobinaemia, Urine drug screen
- Tox Conundrum – Another TCA Overdose!
- Tox Conundrum – Tricyclic antidepressant toxicity
- ECG Library – Overdose: TCA
Critical Care
Compendium
Chris is an Intensivist and ECMO specialist at The Alfred ICU, where he is Deputy Director (Education). He is a Clinical Adjunct Associate Professor at Monash University, the Lead for the Clinician Educator Incubator programme, and a CICM First Part Examiner.
He is an internationally recognised Clinician Educator with a passion for helping clinicians learn and for improving the clinical performance of individuals and collectives. He was one of the founders of the FOAM movement (Free Open-Access Medical education) has been recognised for his contributions to education with awards from ANZICS, ANZAHPE, and ACEM.
His one great achievement is being the father of three amazing children.
On Bluesky, he is @precordialthump.bsky.social and on the site that Elon has screwed up, he is @precordialthump.
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