What are the clinical manifestations and treatment of a doxepin overdose?

Doxepin Overdose: Clinical Manifestations and Management

Critical Manifestations

Doxepin overdose presents with life-threatening cardiac dysrhythmias, severe hypotension, convulsions, and CNS depression including coma, with toxicity developing rapidly and requiring immediate hospital monitoring. 1

Cardiovascular Manifestations

• Cardiac dysrhythmias are the most critical feature, with QRS widening on ECG being the most clinically significant indicator of tricyclic antidepressant toxicity 1
• Severe hypotension develops due to alpha-adrenergic blockade and direct myocardial depression 1
• QRS duration ≥0.10 seconds on maximal limb-lead ECG is the best indication of overdose severity 1
• Fatal dysrhythmias can occur late after overdose, even in patients who initially appeared stable 1

Neurological Manifestations

• CNS depression progressing to coma is a dominant feature, with prolonged toxic coma possible lasting 5-7 days before return of consciousness 1, 2
• Seizures occur and require immediate control 1
• Confusion, disturbed concentration, and transient visual hallucinations are common 1
• Agitation, hyperactive reflexes, stupor, drowsiness, and muscle rigidity may be present 1
• Dilated pupils occur due to anticholinergic effects, though transient anisocoria has been reported 1, 2

Other Clinical Features

• Vomiting is common 1
• Hypothermia or hyperpyrexia may develop 1
• Anticholinergic syndrome: dry mouth, urinary retention, decreased bowel sounds, hyperthermia 1

Immediate Management Algorithm

Step 1: Stabilization and Monitoring (First Priority)

• Obtain ECG immediately and initiate continuous cardiac monitoring for minimum 6 hours, extended if any signs of toxicity appear 1
• Protect airway, establish IV access, and prepare for intubation - early intubation is advised in patients with CNS depression due to potential for abrupt deterioration 1
• Monitor for CNS/respiratory depression, hypotension, cardiac dysrhythmias, conduction blocks, and seizures 1

Step 2: Gastrointestinal Decontamination

• Perform large volume gastric lavage followed by activated charcoal in all suspected cases 1
• Secure airway prior to lavage if consciousness is impaired 1
• Emesis is contraindicated 1

Step 3: Cardiovascular Management

• Administer IV sodium bicarbonate to maintain serum pH 7.45-7.55 for QRS widening or dysrhythmias 1, 3
• If pH response inadequate, add hyperventilation with extreme caution and frequent pH monitoring (avoid pH >7.60 or pCO2 <20 mmHg) 1
• For dysrhythmias unresponsive to sodium bicarbonate, use lidocaine, bretylium, or phenytoin 1
• Type 1A and 1C antiarrhythmics (quinidine, disopyramide, procainamide) are contraindicated 1
• Sodium bicarbonate readily corrects potentially life-threatening cardiac arrhythmias and is imperative in treatment 3

Step 4: Seizure Management

• Control seizures with benzodiazepines as first-line therapy 1
• If benzodiazepines ineffective, use phenobarbital or phenytoin 1
• Physostigmine is NOT recommended except for life-threatening symptoms unresponsive to other therapies, and only in consultation with poison control 1

Step 5: Refractory Cases

• Consider ECMO for refractory shock unresponsive to pharmacological support 4
• Hemoperfusion may benefit acute refractory cardiovascular instability in rare instances 1
• Hemodialysis, peritoneal dialysis, exchange transfusions, and forced diuresis are generally ineffective 1

Critical Pitfalls to Avoid

• Do not rely on plasma drug level monitoring to guide management - clinical presentation and ECG findings are paramount 1
• Do not discharge patients after only brief observation - fatal dysrhythmias can occur late, and most deaths involved inadequate GI decontamination 1
• Combined overdoses enhance toxic effects - doxepin with other CNS depressants (benzodiazepines, neuroleptics) increases risk of severe complications and prolonged coma 3, 4, 2
• Patients with minor sedation and normal QRS width can still develop major complications - maintain high index of suspicion 5
• Contact poison control center (1-800-222-1222 in US) for current treatment guidance as management is complex and evolving 1

Post-Resuscitation Care

• Psychiatric referral is appropriate as overdose is often deliberate and patients may attempt suicide by other means during recovery 1
• Extended monitoring required if any toxicity signs develop during initial 6-hour observation period 1