Pharmacology & Poisoning
Question 179 of 180
A 34 year old woman is brought to the Emergency Department by her husband. He found her at home surrounded by empty fluoxetine packets and a suicide note. She appears to have been storing her fluoxetine prescription. There is no indication of her taking any medication other than fluoxetine. She has no past medical history aside from depression. On examination she is restless and agitated, you note a tremor in both legs and marked diaphoresis. Her observations are recorded as:
- Heart rate: 123 beats per minute
- Blood pressure: 156/104 mmHg
- Respiratory rate: 24 breaths per minute
- Oxygen saturations: 100% on air
- Temperature: 40.6°C
What treatment should be considered in this patient?
Answer:
The patient has features of serotonin syndrome, secondary to SSRI overdose. Standard treatment of serotonin toxicity is benzodiazepines. Most mild cases will resolve spontaneously within 24 hours. In serious cases consider cyproheptadine and chlorpromazine. These are 5HT2A antagonists and have successfully been used to treat serotonin toxicity following overdose but there are no controlled trials to support the use of either agent.Selective Serotonin Reuptake Inhibitor (SSRI) Toxicity
Pharmacology & Poisoning
Last Updated: 14th February 2021
Clinical features
- Clinical features may include GI upset, tremor, agitation, diaphoresis, dizziness, dilated pupils, drowsiness, convulsions and coma.
- Cardiovascular features include tachycardia, hypotension, hypertension, QT and QRS prolongation and Torsade de Pointes.
- Rhabdomyolysis may occur late in the presentation and in the absence of seizures. Other features include hepatotoxicity and hypoglycaemia.
- Serotonin toxicity
- Serotonin toxicity typically occurs when patients are exposed to two or more drugs that increase the effect of serotonin on serotonergic synapses
- Features include CNS effects, autonomic instability, and neuromuscular excitability:
- CNS effects: Features may include agitation, confusion, delirium, and hallucinations. Drowsiness and coma may occur in severe cases.
- Autonomic instability: Features include tachycardia, fever and hypertension or hypotension. Flushing, diarrhoea and vomiting are also common.
- Neuromuscular instability: Features include profound shivering, tremor, teeth grinding, myoclonus and hyperreflexia.
- In severe cases convulsions, hyperthermia, rhabdomyolysis, acute kidney injury, coagulopathies and multi-organ failure may develop.
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 for children) if the patient presents within 1 hour of ingestion of a toxic dose providing it is safe to do so and the airway can be protected. Efficacy declines rapidly with time since ingestion but there may be some potential benefit from later use, especially following ingestion of sustained release preparations or large ingestions.
- This agent is cardiotoxic and can cause QT prolongation and torsade de pointes. Perform a 12-lead ECG in all patients who require assessment. Repeat 12-lead ECGs are recommended, especially in symptomatic patients or in those who have ingested sustained release preparations. Check cardiac rhythm, QRS duration and QT interval.
- Check serum potassium, magnesium and calcium concentrations and replace as necessary to keep within the high normal range. Check ABGs and correct any hypoxia or acidosis. Review all medications that may prolong QT interval. Assess risk of torsade de pointes using QT-HR nomogram.
- Torsade de pointes and VT/VF preceded by a prolonged QT interval should be treated urgently with magnesium sulphate. Consider magnesium sulphate when the QT-heart rate nomogram indicates a risk of torsade de pointes, especially if other risk factors are present. Note that while magnesium sulphate may terminate torsade de pointes, it does not shorten the QT interval.
- All patients should be observed for at least 6 hours after ingestion. Patients who are asymptomatic at 6 hours, with a normal heart rate and ECG, and no serotonergic features, can be considered for discharge with advice to return if symptoms develop. Symptomatic patients should be observed until symptoms are resolved.
- In symptomatic patients check U&Es, glucose, LFTs and CK. Ensure adequate hydration to maintain a good urine output (0.5 mL/kg/hour) and perfusion.
- Agitation and delirium
- Where available, follow local guidelines for treatment of agitation and delirium. The primary goal of management is to keep patient and staff safe while allowing continued evaluation. Attempt de-escalation by reducing environmental stimuli (e.g. quiet room) and providing basic needs (e.g. a close relative, a warm blanket and food (if appropriate)).
- Serotonin toxicity
- Standard treatment of serotonin toxicity is benzodiazepines. Most mild cases will resolve spontaneously within 24 hours. In serious cases consider cyproheptadine and chlorpromazine. These are 5HT2A antagonists and have successfully been used to treat serotonin toxicity following overdose but there are no controlled trials to support the use of either agent.
- Hyperthermia
- Mild to moderate hyperthermia may respond to conventional cooling measures (e.g. mist and fan techniques, ice packs to groin and axillae, external cooling devices). When rising body temperature exceeds 38 degrees C, urgent cooling measures with regular monitoring of core temperature should be employed according to local protocols (e.g. ice-baths, cold fluid lavage, intravascular cooling techniques). Rapid sequence intubation with paralysis is usually warranted when the temperature is rising rapidly and is not controlled by the above measures. On-going neuromuscular paralysis, and sedation with a benzodiazepine infusion, is recommended in addition to cooling measures as per local protocols. Dantrolene may be considered where there is muscular hyperactivity.
- Convulsions
- Single brief convulsions do not require treatment. Control convulsions that are frequent or prolonged with intravenous diazepam, lorazepam, or midazolam.
- 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. Vasopressors and inotropes can be initiated in an emergency through peripheral venous access. THIS SHOULD ONLY BE DONE UNDER THE DIRECTION OF AN EXPERIENCED PHYSICIAN (SpR AND ABOVE).
- Rhabdomyolysis
- If rhabdomyolysis is present (CK activity greater than 5 x the upper limit of the normal range), renal failure can develop, particularly if the CK activity is greater than 5000 iu/L. Give intravenous volume replacement as soon as possible and continue in order to maintain an adequate urine output (≥1ml/kg/h). Consider the need for urine alkalinisation. Haemodialysis / haemodiafiltration / haemofiltration may be required if acute renal failure develops or severe hyperkalaemia is present.
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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 |
