Hot and agitated

Case
33 year old male
gradual onset of confusion, agitation distress; increasing over the past 6-12 hours
recent GP visit for ? depression; question over possible recreational drug use (cannabis, ecstasy)

On arrival in ED (RESUS)
A- patent, protected
B- RR 21/min; SpO2 98% OA ; clear chest
C- hot to touch;  HR 135 bpm; BP 160/100 mmHg
D- agitated, restless, confused; pupils large (mydriasis) / Rigidity limbs, frequent myoclonic jerking movements / hyperreflexia; no meningism
E- temp 38.2; no rash

VBG - mild metabloic acidosis, lactate raised, glucose normal
CXR normal
ECG

What is the differential diagnosis?
What are the potential underlying causes?
What is the treatment?

Ref: Boyer EW, Shannon M. The serotonin syndrome. N Engl J Med. 2005;352:(11)1112-20.

Differential diagnosis
1. toxins
2. encephalopathies (including infection)
3. psychiatric disorders
​4. malignant hyperthermia

Consider in acute behavioural disturbance

Clinical Features of Serotonin Syndrome     ‘CAN’
Central nervous system
- AMS, seizures
Autonomic dysfunction
- HTN, hypotension, tachycardia, bradycardia, hyperthermia, dysrhythmias, flushing, sweating, mydriasis
Neuromuscular dysfunction
​- rigidity LL>UL; hyperreflexia; clonus; tremor

Hunter serotonin toxicity criteria (~ 84% sensitivity) Credit: patient.info

In practice, the diagnosis is often more of a gestalt impression based of the history, absence of other causes and the findings on physical examination.

Potential underlying causes?
Serotonergic agents either in overdose or a combination of therapeutic agents
- Antodepressants: SSRIs  & SNRIs (fluoxetine, citalopram, venlafaxine, duloxetine); TCAs; MAOIs
- opioids (tramadol, pethidine, fentanyl, dextromethorphan)
- antibiotics (linezolid)
- antimemetics (metoclopramide, ondansetron)
- mood stabilisers (lithium, sodium valproate) 
- recreational (amphetamines, ecstacy, LSD)
- herbal (st john’s wart, ginseng) 

Treatment
(RESUS-RSI-DEAD approach)
RESUS
- identify immediately life threats

• decreased level of consciousness
• rigidity, hyperthermia and hypercapnia: requires intubation, ventilation and neuromuscular blockade
• seizures

- airway, breathing, circulation

• administer oxygen
• check cardiac rhythm and output
• establish IV access

- check & correct hypoglycaemia
-  control ongoing seizures (BDZ; Phenytoin; intubation & ventilation)
- correct hyperthermia

• continuously monitor if T>38.5 C
• consider intubation and ventilation with neuromuscular blockade if T >39.5 C

- Discontinue and avoid further administration of serotonergic agents
RISK ASSESSMENT

• this patient has serotonin syndrome probably due to a combination of antidepressants and recreational drugs. It is likely to resolve over 1-2 days. 
• Hyperthermia can lead to metabolic acidosis, rhabdomyolysis, acute kidney injury and disseminated intravascular coagulation.
  
  • Thermal disturbance should be aggressively managed. 
    
  • Antipyretic agents have no role, as hyperthermia is due to muscular activity rather than hypothalamic mechanisms
    

SUPPORTIVE CARE AND MONITORING

• reassurance and careful observation
• fluid management
• agitation, hypertension and tachycardia – usually responds to benzodiazepines
• consider the potential for rhabdomyolysis 

INVESTIGATIONS

• VBG, FBC, U&E, LFT, Paracetamol levels
• ECG
• Check for complications: CK, urinalysis
• CTH if appropriate (trauma, infection)

DECONTAMINATION

• activated charcoal (50g PO/NG) should only be administered if the airway is secure and will remain so (e.g. post intubation)

ENHANCED ELIMINATION (nil)
ANTIDOTES

• Benzodiazepines are the mainstay of treatment
• Serotonin antagonists (see toxbase for more information) 
  • chlorpromazine — 25-100mg in 100 mL normal saline over 30-60 minutes
  • cyproheptadine
    — consider if prolonged or benzodiazepine-resistant
    — 12mg NG, if clinical response noted administer 8mg q8h for 24h

DISPOSITION 

• very mild cases may be discharged with symptomatic treatment, reassurance and appropriate follow up (e.g. GP or mental health team).
• patients with abnormal mental state or vital signs require admission (usually for about 24h) for observation, supportive care and pharmacotherapy until symptoms resolve.
• severe cases require ICU level care (e.g. intubation and ventilation).
• patients at risk of serotonin syndrome due to a deliberate self-poisoning should be observed for at least 8 hours and not discharged at night. This may vary depending on the risk assessment of the specific agent ingested.

Resources & further reading:
https://patient.info/doctor/serotonin-syndrome  
https://lifeinthefastlane.com/toxicology-conundrum-024/
http://www.emdocs.net/serotonin-syndrome-and-neuroleptic-malignant-syndrome-pearls-pitfalls/
http://www.emdocs.net/toxcard-differentiating-serotonin-syndrome-neuroleptic-malignant-syndrome/
https://emsimcases.com/2017/06/20/serotonin-syndrome/
http://foamcast.org/2015/05/04/episode-28-neuroleptic-malignant-syndrome-serotonin-syndrome-malignant-hyperthermia/
https://www.aliem.com/2012/01/paucis-verbis-serotonin-syndrome/
http://www.tamingthesru.com/blog/annals-of-b-pod/spring-2017/serotonin-syndrome