Makindo Medical Notes

Related Subjects: Acute Kidney Injury |Acute Rhabdomyolysis |Hyperkalaemia |Neuroleptic Malignant Syndrome |Malignant Hyperpyrexia (Malignant Hyperthermia) |Parkinson Hyperpyrexia Syndrome |Serotonin syndrome |Cholinergic crisis-syndrome |Anticholinergic syndrome

Serotonin Syndrome is a potentially life-threatening drug-induced condition caused by excessive serotonergic activity. It classically presents with a triad of:

1. Altered mental status 🧠
2. Autonomic instability ⚡
3. Neuromuscular hyperactivity 💪

Aetiology

• Serotonin (5-HT) is widely distributed in the CNS, gut, and platelets. It regulates mood, appetite, sleep, pain, and autonomic tone.
• Excess serotonin → hyperstimulation of 5-HT1A and 5-HT2A receptors → neuromuscular overactivity, hyperthermia, and autonomic disturbance.
• CNS effects: agitation, delirium, seizures. PNS effects: diarrhoea, hyperreflexia, sweating, vasoconstriction.
• Overstimulation is acute (hours, not days) — key exam pearl vs NMS.

Causes (Drugs & Interactions) 💊

• Antidepressants: SSRIs, SNRIs, MAOIs, TCAs, mirtazapine, trazodone.
• Opiates: Tramadol, pethidine, fentanyl, oxycodone, buprenorphine.
• CNS stimulants: MDMA (“ecstasy”), amphetamines, cocaine, sibutramine.
• Other drugs: Lithium, valproate, buspirone, linezolid, metoclopramide, ondansetron, chlorpheniramine, atypical antipsychotics.
• Herbal products: St John’s Wort, ginseng, nutmeg.

Clinical Features 🩺

• Neuromuscular: Hyperreflexia, inducible/ocular clonus, myoclonus, tremor, rigidity (lower limbs > upper limbs). Key differentiator vs NMS.
• Autonomic: Hyperthermia (>40°C), tachycardia, hypertension, diaphoresis, diarrhoea, mydriasis.
• Mental state: Agitation, confusion, delirium, seizures, coma in severe cases.
• Complications: Rhabdomyolysis → AKI; DIC; metabolic acidosis; shock. ⚠️

Diagnosis 🔎

• Hunter Criteria (most specific, exam favourite):
  • On serotonergic agent + one of the following:
  • Spontaneous clonus
  • Inducible clonus + agitation/diaphoresis
  • Ocular clonus + agitation/diaphoresis
  • Tremor + hyperreflexia
  • Hypertonia + temp >38°C + ocular/inducible clonus
• Differential diagnoses:
  • NMS: Slower onset (days), “lead-pipe” rigidity, normal reflexes.
  • Malignant Hyperthermia: Triggered by anaesthetics, calcium dysregulation.
  • Sepsis, anticholinergic toxicity, CNS infections may mimic features.

Investigations 🔬

• Bloods: FBC, U&E, LFTs, glucose, CRP, lactate, CK (for rhabdomyolysis).
• ABG: Assess metabolic acidosis.
• ECG: Arrhythmias, QT prolongation.
• Urinalysis: Myoglobinuria if rhabdomyolysis.
• CXR/CT head if differential diagnoses suspected (encephalitis, sepsis).

Management 💉

Early toxicology/ICU consultation is essential in severe cases.

• Initial: Stop serotonergic drugs immediately. Secure ABCs. Admit to HDU/ICU if severe.
• Agitation/seizures: IV benzodiazepines (diazepam 5–10 mg, lorazepam 2–4 mg). Large doses may be required.
• Temperature: Aggressive cooling (ice packs, cooled IV fluids). ❌ Avoid antipyretics (paracetamol ineffective).
• Fluids: IV crystalloids (1–2 L initially) to prevent dehydration, rhabdomyolysis-induced AKI.
• Serotonin antagonists: Cyproheptadine (PO/NG) — 12 mg stat, then 8 mg q6h. Rare but exam high-yield.
• Other agents: Chlorpromazine (serotonin antagonist, rarely used); Dantrolene only if severe hyperthermia/muscle rigidity not controlled.
• Complications:
  • Rhabdomyolysis: IV fluids + consider bicarbonate to alkalinise urine.
  • Hypoglycaemia: IV glucose.
  • Hyperkalaemia from muscle breakdown: treat accordingly.

Prognosis 📉

• Most cases resolve within 24h of stopping serotonergic drugs + supportive care.
• Severe untreated cases → hyperthermia, seizures, multi-organ failure, death.
• Mortality is rare if recognised early.

Exam Pearls ✨

• 🧪 Hunter criteria > Sternbach criteria (better specificity).
• ⚡ Clonus + hyperreflexia = serotonin syndrome. Lead-pipe rigidity = NMS.
• ❌ Antipyretics ineffective — must use active cooling.
• 💊 Cyproheptadine is exam buzzword but not always available in practice.
• 📅 Onset: hours (SS) vs days (NMS) — key OSCE discriminator.

References

• NHS Lothian: Serotonin Syndrome Guideline
• Serotonin Syndrome: Pathophysiology, Clinical Features, Management
• TOXBASE: UK National Poisons Information Service database