Pharmacology & Poisoning
A 64 year old man is brought to the Emergency Department by his husband. He found him at home surrounded by empty amitriptyline packets and a suicide note. He appears to have been storing his amitriptyline prescription. There is no indication of him taking any medication other than amitriptyline. What treatment may be indicated in this patient?
Answer:
In adults consider immediate administration of 50 – 100 mL of 8.4% sodium bicarbonate if the patient has the following conditions even in the absence of acidosis: QRS of greater than 120 msec or hypotension unresponsive to fluids. Recheck acid base status and 12 lead ECG after administration of sodium bicarbonate. Give further sodium bicarbonate if QRS prolongation remains, especially if there is persistent acidosis, guided by arterial blood gas monitoring.Tricyclic Antidepressant Toxicity
Pharmacology & Poisoning
Last Updated: 12th February 2021
Tricyclic antidepressants are highly toxic by ingestion; fatal cardiac arrhythmias may occur soon after ingestion. Toxicity is due to a combination of anticholinergic (antimuscarinic, atropine-like) effects at autonomic nerve endings and in the brain, cardiac sodium channel blockade and alpha 1 adrenergic receptor blockade. In addition, tricyclic antidepressants block presynaptic uptake of amines and the cardiac delayed rectifier potassium channel (Ikr).
Ingestion of 15 mg/kg would be expected to result in serious, potentially life-threatening symptoms.
Clinical features
Severe toxicity occurs from sodium channel blockade and may cause arrhythmias, cardiovascular collapse, convulsions and coma.
Features include those of anticholinergic toxicity: sinus tachycardia, confusion, drowsiness, hot dry skin, dry mouth and tongue, dilated pupils, urinary retention and ileus. Ataxia, nystagmus, divergent squint, and myoclonus may occur.
In severe cases, central nervous system depression may progress rapidly to deep coma, with convulsions, respiratory depression and respiratory arrest. Adult respiratory distress syndrome may develop. Convulsions may herald cardiovascular shock.
ECG features include prolongation of the PR, QRS and QT intervals, non-specific ST segment and T wave changes, and atrioventricular block. Brugada electrocardiographic pattern has been reported. Prolonged QRS is a predictor of convulsions and ventricular arrhythmias.
Hypotension, hypokalaemia and metabolic acidosis may occur. Hypothermia and rhabdomyolysis, and occasionally skin blisters, may occur in patients who have been unconscious.
Increased tone and hyperreflexia may be present with extensor plantar reflexes. In deep coma, all reflexes (including brainstem reflexes) may be abolished.
Management
- Maintain a clear airway and ensure adequate ventilation.
- The benefit of gastric decontamination is uncertain. Consider activated charcoal (charcoal dose: 50 g for adults, 1 g/kg body weight for children) by mouth or nasogastric tube if the patient presents within 1 hour of ingesting a toxic dose or more provided the airway can be protected. A second dose of charcoal (charcoal dose: 50 g for adults; 1 g/kg body weight for children) should be considered after 1-2 hours in patients with features of toxicity who are able to swallow, or who have been intubated.
- In adults consider immediate administration of 50 – 100 mL of 8.4% sodium bicarbonate if the patient has the following conditions even in the absence of acidosis: QRS of greater than 120 msec or Hypotension unresponsive to fluids. Recheck acid base status and 12 lead ECG after administration of sodium bicarbonate. Give further sodium bicarbonate if QRS prolongation remains, especially if there is persistent acidosis, guided by arterial blood gas monitoring.
- All patients who require assessment should be observed for at least 6 hours after exposure.
- Metabolic acidosis
- If metabolic acidosis persists despite correction of hypoxia and adequate fluid resuscitation consider correction with intravenous sodium bicarbonate. Rapid correction is particularly important if there is prolongation of the QRS interval.
- Convulsions
- Give oxygen; check blood glucose, U&Es, calcium, magnesium, phosphate and ABG. Correct acid base and metabolic disturbances as required. Control convulsions that are frequent or prolonged with intravenous benzodiazepines.
- Hypotension
- Ensure adequate fluid resuscitation. Treat brady and tachyarrhythmias appropriately. Consider early referral to critical care for patients with fluid-resistant hypotension, as these patients can deteriorate extremely rapidly. Glucagon is a treatment option for severe hypotension, heart failure or cardiogenic shock.
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- Biochemistry
- Blood Gases
- Haematology
| Biochemistry | Normal Value |
|---|---|
| Sodium | 135 – 145 mmol/l |
| Potassium | 3.0 – 4.5 mmol/l |
| Urea | 2.5 – 7.5 mmol/l |
| Glucose | 3.5 – 5.0 mmol/l |
| Creatinine | 35 – 135 μmol/l |
| Alanine Aminotransferase (ALT) | 5 – 35 U/l |
| Gamma-glutamyl Transferase (GGT) | < 65 U/l |
| Alkaline Phosphatase (ALP) | 30 – 135 U/l |
| Aspartate Aminotransferase (AST) | < 40 U/l |
| Total Protein | 60 – 80 g/l |
| Albumin | 35 – 50 g/l |
| Globulin | 2.4 – 3.5 g/dl |
| Amylase | < 70 U/l |
| Total Bilirubin | 3 – 17 μmol/l |
| Calcium | 2.1 – 2.5 mmol/l |
| Chloride | 95 – 105 mmol/l |
| Phosphate | 0.8 – 1.4 mmol/l |
| Haematology | Normal Value |
|---|---|
| Haemoglobin | 11.5 – 16.6 g/dl |
| White Blood Cells | 4.0 – 11.0 x 109/l |
| Platelets | 150 – 450 x 109/l |
| MCV | 80 – 96 fl |
| MCHC | 32 – 36 g/dl |
| Neutrophils | 2.0 – 7.5 x 109/l |
| Lymphocytes | 1.5 – 4.0 x 109/l |
| Monocytes | 0.3 – 1.0 x 109/l |
| Eosinophils | 0.1 – 0.5 x 109/l |
| Basophils | < 0.2 x 109/l |
| Reticulocytes | < 2% |
| Haematocrit | 0.35 – 0.49 |
| Red Cell Distribution Width | 11 – 15% |
| Blood Gases | Normal Value |
|---|---|
| pH | 7.35 – 7.45 |
| pO2 | 11 – 14 kPa |
| pCO2 | 4.5 – 6.0 kPa |
| Base Excess | -2 – +2 mmol/l |
| Bicarbonate | 24 – 30 mmol/l |
| Lactate | < 2 mmol/l |
