Overview

Definition:
-Tricyclic antidepressant (TCA) overdose is a life-threatening condition characterized by excessive ingestion of TCAs, leading to a spectrum of neurological and cardiovascular toxicity
-Sodium bicarbonate is a cornerstone therapy in managing the cardiotoxicity associated with TCA overdose.
Epidemiology:
-While TCA overdose incidence has decreased with newer antidepressants, they remain a significant cause of poisoning-related deaths
-Pediatric ingestions are often accidental, though intentional overdoses can occur in adolescents
-The severity is dose-dependent and influenced by individual metabolism.
Clinical Significance:
-TCA overdose is a medical emergency due to its potential for rapid deterioration, particularly cardiac conduction abnormalities and seizures
-Prompt and accurate management, including the judicious use of sodium bicarbonate, is critical to preventing morbidity and mortality in pediatric patients, and is a high-yield topic for DNB and NEET SS examinations.

Clinical Presentation

Symptoms:
-Dry mucous membranes
-Blurred vision
-Urinary retention
-Sedation or coma
-Seizures
-Agitation or delirium
-Tachycardia
-Hypotension
-Flushing.
Signs:
-Vital signs: Tachycardia (often sinus tachycardia), hypotension, hyperthermia
-Neurologic: Altered mental status ranging from lethargy to deep coma, myoclonus, hyperreflexia, seizures
-Cardiovascular: QRS widening (>100 ms), prolonged QT interval, arrhythmias (ventricular tachycardia, torsades de pointes, asystole), decreased myocardial contractility
-Anticholinergic toxidrome: dry skin/mucous membranes, flushed skin, mydriasis, urinary retention, decreased bowel sounds.
Diagnostic Criteria:
-Diagnosis is primarily clinical, based on suspected ingestion and characteristic signs and symptoms
-A history of TCA ingestion, coupled with anticholinergic and cardiotoxic manifestations, strongly suggests TCA overdose
-ECG findings of QRS widening are highly suggestive and a key indicator for management decisions.

Diagnostic Approach

History Taking:
-Inquire about the specific TCA ingested (e.g., amitriptyline, nortriptyline, imipramine, clomipramine), the amount ingested, the time of ingestion, and any co-ingestions
-Note any pre-existing cardiac or neurological conditions in the child
-Confirm any recent psychiatric history or stressors in adolescents.
Physical Examination:
-Perform a rapid assessment of airway, breathing, and circulation (ABC)
-Assess mental status (Glasgow Coma Scale)
-Examine for anticholinergic signs
-Auscultate heart and lungs
-Palpate abdomen for distension
-Assess for neurological deficits and signs of seizures.
Investigations:
-Serum TCA levels are often not readily available or helpful for acute management decisions
-The ECG is paramount: assess QRS duration (≥100 ms indicates increased risk of seizures and arrhythmias), QT interval, and rhythm
-Serum electrolytes (including bicarbonate), glucose, renal function, and liver function tests are important
-Arterial blood gas (ABG) analysis to assess for acidosis
-Consider toxicology screen for co-ingestions.
Differential Diagnosis:
-Other anticholinergic poisonings (e.g., atropine, scopolamine, antihistamines)
-Sympathomimetic overdose (e.g., amphetamines, cocaine)
-Opioid overdose
-Sedative-hypnotic overdose
-Metabolic encephalopathy
-Sepsis.

Management

Initial Management:
-Ensure ABCs are secured
-Administer activated charcoal if ingestion is recent (<1-2 hours) and the patient is conscious and able to protect their airway
-Gastric lavage is rarely indicated and may be harmful
-Monitor vital signs, cardiac rhythm, and neurological status closely
-IV access is crucial.
Medical Management:
-Sodium bicarbonate: Administer a bolus of 1-2 mEq/kg IV push, aiming for a serum pH of 7.45-7.55 and a QRS duration <100 ms
-Repeat boluses as needed, titrating to ECG changes and pH
-Continuous infusion of sodium bicarbonate may be used to maintain alkalosis and prolong QRS narrowing
-Treatment of seizures: Benzodiazepines (e.g., diazepam, lorazepam) are first-line
-If seizures persist or are refractory, consider phenobarbital or phenytoin
-Management of arrhythmias: Treat hypotension with IV fluids and vasopressors (e.g., norepinephrine)
-Avoid antiarrhythmics that prolong QRS duration (e.g., flecainide, propafenone)
-Lidocaine may be used cautiously for ventricular arrhythmias if sodium bicarbonate is ineffective
-Hyperthermia management: Cooling measures such as cooling blankets, fans, and antipyretics (avoiding salicylates).
Surgical Management:
-Not applicable for TCA overdose management
-Focus is on supportive and medical interventions.
Supportive Care:
-Continuous cardiac monitoring with telemetry
-Frequent neurological assessments
-Maintain oxygenation and ventilation
-Provide adequate hydration
-Monitor urine output
-Consider nasogastric tube for gastric decompression if ileus develops
-Monitor fluid balance to avoid hyponatremia with bicarbonate therapy.

Complications

Early Complications:
-Refractory seizures (status epilepticus)
-Fatal cardiac arrhythmias (ventricular tachycardia, torsades de pointes, asystole)
-Respiratory arrest
-Pulmonary edema
-Rhabdomyolysis
-Acute kidney injury
-Hyperthermia
-Cerebral edema.
Late Complications:
-Neurological sequelae from prolonged seizures or hypoxic brain injury
-Cognitive deficits
-Peripheral neuropathy
-Chronic pain syndromes
-Psychiatric sequelae related to underlying conditions.
Prevention Strategies:
-Secure storage of medications away from children
-Prescription of smaller quantities of TCAs for outpatients
-Patient and caregiver education regarding the dangers of overdose
-Close psychiatric monitoring for adolescents at risk.

Prognosis

Factors Affecting Prognosis:
-The amount and type of TCA ingested, time to initiation of treatment, presence and severity of cardiovascular toxicity (QRS widening, arrhythmias), and occurrence of seizures are critical prognostic factors
-Rapid response to sodium bicarbonate is a positive indicator.
Outcomes:
-With prompt and aggressive management, including sodium bicarbonate for cardiotoxicity, many pediatric patients can recover
-However, severe overdoses can lead to significant morbidity or mortality
-A QRS duration >100 ms on ECG in TCA overdose is associated with a higher risk of seizures and cardiac arrhythmias.
Follow Up:
-Long-term follow-up should address any underlying psychiatric issues that may have contributed to the overdose
-Neurological assessments may be required if seizures or significant CNS depression occurred
-Renal and liver function should be re-evaluated as needed.

Key Points

Exam Focus:
-The hallmark ECG finding of TCA overdose is QRS widening (>100 ms)
-Sodium bicarbonate is the primary treatment for cardiotoxicity
-Aim for serum pH 7.45-7.55 and QRS <100 ms
-Seizures are treated with benzodiazepines.
Clinical Pearls:
-Never assume a non-toxic ingestion in a pediatric TCA overdose
-always treat aggressively
-Serial ECGs are crucial to monitor response to therapy
-Be prepared to manage seizures and arrhythmias aggressively
-Monitor for hyponatremia with aggressive bicarbonate use and fluid management.
Common Mistakes:
-Delaying sodium bicarbonate therapy in the presence of QRS widening
-Using antiarrhythmic drugs that prolong the QRS interval
-Underestimating the severity of TCA overdose
-Inadequate monitoring of ECG and vital signs.