see also: [[Heat-related illness#Heatstroke cooling treatment|Active cooling]], [[Hot and bothered]] see: [Murray Serotonin Syndrome](x-devonthink-item://C8AE745C-C96E-4AEF-9010-D441840C6DF4?page=77), [Austin Serotonin Syndrome](https://www.austin.org.au/Assets/Files/Serotonin%20Toxicity%20guideline_March2023.pdf), [Illicit Drug Induced Hyperthermia - EMA 2025](bookends://sonnysoftware.com/ref/DL/259320) [Murray DDx of serotonin syndrome table](x-devonthink-item://C8AE745C-C96E-4AEF-9010-D441840C6DF4?page=81) > [!Key Points] > - **risk dose:** note that [[Venlafaxine]] higher risk of seizures! > - Causes:: SSRIs, SNRIs, tramadol, pethidine, amphetamines > - Antidote:: benzos, cyproheptadine > - Cyproheptadine is not a life-saving antidote (see below) > - [mnemonic:: RASCAL] # Risk assessment ## Hunter Criteria ![[Pasted image 20230629141251.png]] Patient took **a known seritonergic agent** AND needs **at least one of the following**: - spontaneous clonus - (inducible clonus OR occular clonus) AND (agitation or diaphoresis ) - (inducible clonus OR occular clonus) AND hypertonia AND temp >38 deg C - Tremor AND hyperreflexia “Agitated or sweaty, or tone and temp. Tremor and reflexes” ![[Pasted image 20241226201538.png]] ≥ 5 features and ≥ 1 from each column # Toxic Mechanism - inhibition of 5-HT metabolism - MAOI, lamotrigine, methylene blue, linezolid - prevention of 5-HT reuptake - SSRI, tramadol, clomipramine - 5-HT release - cathinones, MDMA, amphetamines > usually from one of three clinical settings: > 1. acute overdose of SSRI > 1. when taken in isolation, rarely life-threatening, but bad if taken in combonation > 2. during normal theapeutic drug use > 1. commencing a sterotonergic drug > 2. increasing dose of seritonergic drug > 3. seritonergic synergistic reactions > 1. eg SSRI + pethidine or MAOI # Clinical features See also [[Neuroleptic Malignant Syndrome#differences from serotonin syndrome table|NMS vs serotonin syndrome table]] > the lower limbs usually have a much greater degree of hyperreflexia and clonus than the upper limbs **mild** - tremor, tachycardia, inducible clonus (**ankle**, ocular), hyperreflexia **moderate** - agitation, sustained clonus, hyperthermia <39 deg C **severe** - temp >39 deg C - muscle rigidity - [[seizures]] > severe serotonin tox is a medical emergency and can lead to multi organ failure, especially if MAOI > - usually results from combination of multiple mechanisms **Other complications of serotonin syndrome** - metabolic acidosis - [[rhabdomyolysis]] - [[Acute Renal Failure|AKI]] - [[Seizures]] - [[DIC]] # Treatment **mild** - IV hydration - diazepam 5-10mg Q 2-4 hours **moderate to severe** - aggressive cooling if temp > 39 deg - may require intubation and paralysis consider: chlorpromazine 25mg IV over 1 hour in 1000mL cyproheptadine orally or NGT 12mg loading 2mg Q2H olanzapine 10mg SL/PO ==endpoint of treatment== resolution of neuromuscular excitation and normal vital signs - ==Cyproheptadine is not a life-saving antidote.== It may ameliorate the symptoms of mild-to-moderate serotonin syndrome, but a good outcome will be achieved in these cases with simple supportive care including mild benzodiazepine sedation. - Cyproheptadine is ==not useful in the management of severe serotonin syndrome==. Early intubation and neuromuscular paralysis is the key to achieving a good outcome in this circumstance. - dantrolene and bromocriptine may ==WORSEN== sx due to ↑ CNS serotonin > "Cyproheptadine is to serotonin syndrome as an antihistamine is to anaphylaxis" - Martin Dutch **Severe** - phenothiazines, eg - olanzapine 5mg po/IM - chlorpromazine 50-100mg IM/IV then 50-100mg Q6H - +/- barbituates - intubation, paralysis for thermal control # Disposiiton - tox usually resolves over 24- 48 hours - discharge when clinically well # mnemonic RASCAL [[Rhabdomyolysis]] Agitation / hypervigilance Seizures Clonus Autonomic overdrive - tachycardia, hypertension Large pupils - [[mydriasis]] also... hyperreflexia hyperthermia # Related Questions ## citalopram overdose - [ ] 13Q: [Large Citalopram Overdose](x-devonthink-item://834C484F-DDAA-4819-8DF0-84AE5E70DA1D?page=36) -- [Answer](x-devonthink-item://D46998FE-62E2-4A3A-860D-C32C94B86E42?page=17) -- [prop](x-devonthink-item://834C484F-DDAA-4819-8DF0-84AE5E70DA1D?page=77) ## serotonin syndrome - [ ] 45Q: [Febrile, altered mental status](x-devonthink-item://9C485EF0-3985-4EBA-B9DC-9CDF8A6E2F45?page=12) -- [Answer](x-devonthink-item://A0D348CE-FCD4-4ECD-BE21-6CA73F6DE8CD?page=13) - [ ] 46Q: [Serotonin Syndrome](x-devonthink-item://D6654B01-83AA-4553-94F0-791FD96A636D?page=11) -- [Answer](x-devonthink-item://00427DF6-6D28-4FEB-A0CA-DF96DBBBCE97?page=5) - [ ] 47Q: [Serotonin Syndrome](x-devonthink-item://C88FD92C-E0CB-48A1-8D73-F20489FA4E6C?page=5) -- [Answer](x-devonthink-item://98D17FA0-225B-4E94-B21C-4E36D5C76A7C?page=28)