Serotonin Syndrome

Take home messages

• Serotonin does lots of different things, in the CNS, gut and platelets
• If you have too much of it, you get a triad of autonomic hyperactivity, neuromuscular abnormalities and mental status change
• It's a clinical diagnosis, and there has to be a trigger
• Treatment is mainly supportive and it usually resolves in 24 hours

Serotonin

• Monoamine neurotransmitter made from L-tryptophan
• Plays a role in bronchospasm, platelet aggregation, pain, nausea and vomiting
• Metabolised by monoamine oxidase (MAO)
• Primary metabolite is 5-hydroxyindole acetic acid (5-HIAA), excreted in urine

Serotonin receptors

• 7 classes 5HT_1–7 with different subtypes e.g. 5-HT_2a
• All act via G-Proteins and cAMP, apart from 5HT-3, which acts via a ligand-gated ion channel
• 5HT-3 receptors act in GI tract and CNS to generate emetic response, hence inhibitors of 5HT-3 receptors (like ondansetron) are effective antiemetics

Serotonin Specific Reuptake Inhibitors

• Commonly used medications to boost synaptic serotonin levels
• Best not to stop in perioperative period, but a few missed doses not significant
• Anaesthesia can trigger hypotension, arrhythmias, shivering, and postoperative confusion, albeit rarely
• Probably decrease platelet aggregation but not thought to be clinically significant in perioperative setting

Serotonin syndrome

• Mixture of mental status change, neuromuscular abnormalities, and autonomic hyperactivity
• Occurs within 24 - 48 hours of trigger, usually a change in medications
• Thought to be from hyperstimulation of 5-HT_1a and 5-HT₂ receptors in medulla and central grey nuclei
• Classic triggers are a combination of drugs that boost serotonin levels, including SSRIs, tricyclic antidepressants, MAO inhibitors, and St. John's Wort
• Previously diagnosed according to the Sternbach criteria, either four major or three major plus two minor features must be present

• But Hunter criteria probably better, and so are used more frequently nowadays:

Treatment

• Stop any drugs that increase serotonin
• Supportive therapy
• Self-resolves within 24 hours - rarely fatal - usually good prognosis if spotted early
• Benzodiazepines for anxiolysis and seizures
• Noradrenaline if severely hypotensive
• Cyproheptadine has also been used (antihistamine that also has anti-serotonin activity)

References and Further Reading:

• Sadasivan Chinniah, FRCA, James L.H. French, FRCA, David M. Levy, FRCA, Serotonin and anaesthesia, Continuing Education in Anaesthesia Critical Care & Pain, Volume 8, Issue 2, April 2008, Pages 43–45, https://doi.org/10.1093/bjaceaccp/mkn006
• Bartakke A, Corredor C, van Rensburg A. Serotonin syndrome in the perioperative period. BJA Educ. 2020 Jan;20(1):10-17. doi: 10.1016/j.bjae.2019.10.003. Epub 2019 Dec 4. Erratum in: BJA Educ. 2020 Apr;20(4):139. PMID: 33456910; PMCID: PMC7807833.