Serotonin syndrome – one minute read Serotonin syndrome is a potentially life-threatening condition caused by increased serotonergic activity in the CNS. It is seen with therapeutic medication use, inadvertent drug interaction, intentional self poisoning and illicit drug use Serotonin syndrome can occur in all age groups including newborns and the elderly. The most commonly implicated drugs are SSRIs. Serotonin syndrome has 3 types of clinical manifestations(‘CAN’): •central nervous system: altered mental state (agitation, anxiety, confusion or stupor), seizures •autonomic dysfunction: hypertension or hypotension, tachycardia or bradycardia, hyperthermia, dysrhythmias, flushing, sweating, mydriasis •neuromuscular dysfunction: rigidity (lower limbs more so than upper limbs), hyper-reflexia, clonus (including ocular), tremor, myoclonus Usually improves over 24 hours, ranges from mild, self limited syndrome to rapidly progressive causing organ failure, DIC and death Differential diagnosis: Drugs, poisons and toxins; anticholinergic syndrome, neuroleptic malignant sympathomimetic syndromes, salicylate poisoning, theophyline toxicity Infection; sepsis, encephalopathy Brain disorders; metabolic (thyroid), infective, organic Malignant hyperthermia Amy Adams

Management – serotonin syndrome Resuscitation Patient should be moved into resus whilst identifying immediate life threats: decreased level of consciousness rigidity, hyperthermia and hypercapnea: requires intubation, ventilation and neuromuscular blockade seizures Airway, Breathing, Circulation; administer oxygen, check cardiac rhythm and output, establish IV access, Check for and correct hypoglycaemia Control ongoing seizures: benzodiazepines are first line: diazepam 5-10mg IV, (0.1-0.3 mg/kg in children) repeated as necessary barbiturates are second line: phenobarbitone 100-300mg slow IV (10-20 mg/kg in children) or thiopentone IV 3-5 mg/kg (if intubated and ventilated). Correct hyperthermia; continuously monitor if T>38.5 C and consider I&V with neuromuscular blockade if T >39.5 C. Aggressive external cooling, internal cooling (bladder washouts), invasive cooling (cooling CVC) should be considered. Dantrolene should be considered on the basis it has similar pathogenesis to malignant hyperthermia. Antipyretics are not effective due to muscular activity causing raised temperature not hypothalmic mechanisms. Discontinue any sertonergic agents and avoid further serotonergic agents. Activated charcoal should be considered if the airway is secure and will remain so Antidotes: Benzodiazepines are the mainstay of treatment as noted above, Serotonin antagonists are of unproven efficacy – cyproheptadine should be considered if prolonged or benzodiazepine-resistant (initially 12mg NG/PO then 8mg eight hourly for 24 hours if clinical response) The patient should be moved to a critical care area if ongoing continued monitoring is needed or if organ support is/is likely to be required. Urinary catheterisation and monitoring of fluid balance Intubation may be indicated for airway protection if GCS low and airway unsafe, to manage uncontrolled seizures. Intubation, ventilation and paralysis may be indicated for severe serotonin syndrome independent of the need for airway protection: truncal rigidity impeding ventilation, T>39.5C+, rising PaCO2, rising CK Investigations Bedside testing: ECG (looking for prolonged QTc/arrhythmias associated with ingestion of drugs), BM, blood gas analysis, Cardiac monioring, temperature Bloods: FBC, UEs, CK!!, LFTs, Bicarb if not available on blood gas, TFTs, paracetamol/salicylate if intentional OD Urine: dip, myoglobin, drugs of abuse screening Imaging – dependant on clinical course, if severe and needing lines and intubation – CXR, if uncertain of diagnosis with low gcs or lateralising signs - CTB Complications Hyperthermia can lead to metabolic acidosis, rhabdomyolysis, acute kidney injury and disseminated intravascular coagulation leading to death within a few hours Seizures Respiratory failure Amy Adams