Serotonin toxicity is a serious side effect of ingestion of NPS. Features may occur insidiously over a period of hours to minutes and are characterized by altered mental state, neuromuscular hyperactivity and autonomic instability.
- Altered Mental State – Agitation, confusion, delirium, hallucinations, drowsiness and coma
- Neuromuscular Hyperactivity – shivering, tremor, teeth grinding, myoclonus and hyperreflexia
- Autonomic Instability – Tachycardia, fever, hyper- or hypotension, flushing, diarrhoea and vomiting
In severe toxicity, uncontrolled hyperpyrexia leads to rhabdomyolysis, renal failure, acidosis, hypocalcaemia, hyperkalaemia, DIC and death. It is therefore paramount that it is diagnosed and treated early.
This flow chart can help aid diagnosis of Serotonin Toxicity (Formed from the Hunter Serotonin Toxicity Criteria (Sensitivity 84%, specificity 97%):
Isbister GK, Buckley NA, Whyte IM. Serotonin toxicity: a practical approach to diagnosis and treatment. Med J Aust 2007; 187:361-365
Serotonin Toxicity
*There is no evidence to support the use of Dantrolene effectivement in serotonin toxic patients.
Investigations: (Dictated to by presentation)
Mild toxicity - U&Es, CK, Glucose, VBG, ECG
Moderate / severe toxicity - U&Es, FBC, LFTS, Ca2+, Coag, CK, VBG, Glucose, ECG
Role of urine toxicology - Helpful for surveillance of agents only. Does not change management as most NPS NOT detected.
Cooling:
- Cooled IV fluids and cooled fluids for bladder lavage
- Ice - applied by packing axilla and groin with ice
- Antipyretics have no role for serotonin toxicity induced hyperpyrexia
- Bair Hugger - on cool
RSI
Opiate - avoid Fentanyl/Alfentanil due to serotonergic action
Recommended induction agent:
- Thiopentone 3-5mg/kg (Avoid Ketamine)
Muscle relaxant - Rocuronium 1mg/kg for induction
Depolarising neuromuscular blockers (Suxamethonium) are contraindicated
Hyperkalaemia
- 0.5ml/kg Calcium Gluconate 10%
- Insulin/Dextrose infusion if blood sugar levels normal
Rhabdomyolysis
- IV fluids
- Consider 3-5 mmol/kg of Sodium Bicarbonate (3-5mls/kg of 8.4% NaBic)
Drug Doses
- Midazolam: 0.05-0.1mg/kg IV
- Lorazepam: 0.1mg/kg (4mg max) IV
- Cyproheptadine: PO or crushed and administered via NG
Adults and children aged 13 or more: 12 mg orally, followed by 4-8mg every 6hrs
Children aged 12 years or less: 0.25mg/kg/day (max 12mg) in 4 divided doses
- Chlorpromazine: 500mcg/kg IM 6-12 years, 25-50mg IM 12-18 years
- Dantrolene*: 2-3mg/kg IV
* There is no evidence to support the use of Dantrolene effectiveness in serotonin toxic patients.
Important points about management of serotonin toxicity management:
- Mortality is significantly raised in patients with a temperature >40oC
- Cyproheptadine and chlorpromazine are unlicenced for this use. Their use treats symptoms but as yet do not alter mortality.
- Acute kidney injury, liver failure, disseminated intravascular coagulation, rhabdomyolysis are complications associated with moderate to severe serotonin toxicity.
- Toxicology studies of NPS are extremely limited.
- NPS have a greater duration of effect than ecstasy.
If the child has completed period of observation and is deemed medically fit for discharge please refer to the ‘intoxicated’ child/adolescent flow chart