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AMS, Hyperthermia, Hyperreflexia? How to Nail This Clinical Diagnosis

October 19, 2022

Written by Gabby Leonard

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Here are the clinical clues to keep you from missing serotonin syndrome (SS) and pearls to treat it once you make the diagnosis.

Why does this matter?
SS is an uncommon, often-missed, life-threatening disease with significant morbidity and mortality when not identified and treated immediately.

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SS is a clinical diagnosis that is often missed or confused with other disease processes due to its variable presentation. The triad of symptoms includes neuromuscular excitation (often presenting as clonus in the lower extremities, hyperreflexia, rigidity or opsoclonus), autonomic dysfunction (tachycardia, hypo- or hypertension, hyperthermia, and diarrhea), as well as altered mental status (delirium, agitation or coma). Mild presentations may present as headache, restlessness, and dizziness, but in the most severe form, patients may develop rhabdomyolysis, seizures and end organ damage.

A wide range of medications may cause SS including SSRIs, SNRIs, fentanyl, ondansetron, triptans, linezolid, tramadol, dextromethorphan, bupropion, and more. Many of these are used routinely for acute treatment of pain and nausea in the ED and may exacerbate patients’ symptoms. Symptom onset occurs 12-24 hours after medication exposure or dose adjustment.

Workup should evaluate for alternative infectious etiologies, electrolyte or thyroid abnormalities, EKG changes (QRS or QT prolongation), rhabdomyolysis, coagulopathy such as DIC, intracranial abnormality, co-ingestion, or other toxidrome.

Treatment includes benzodiazepines and IV fluids as well as rapid cooling to achieve normothermia, which has been associated with improved survival. Cyproheptadine may have some benefit in mild cases but can worsen autonomic dysfunction due to its anticholinergic properties in severe cases. If intubation is required, use a non-depolarizing paralytic such as rocuronium.

Source
High risk and low prevalence diseases: Serotonin syndrome. Am J Emerg Med. 2022 Aug 20;61:90-97. doi: 10.1016/j.ajem.2022.08.030. Online ahead of print.

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