This document describes the case of a 53-year-old lady brought in with altered mental status and fever. Her symptoms worsened after 12 hours, with increased confusion and rigidity. This was likely caused by neuroleptic malignant syndrome (NMS), a rare but serious reaction to antipsychotic drugs. NMS requires immediate withdrawal of antipsychotics, supportive care, and may include benzodiazepines or dopaminergic drugs. Careful monitoring is needed if antipsychotics are reintroduced.

2. Case Scenario
• Clinical approach
Case discussion:
• Differential diagnosis
• Investigations
• Management

3. 53yrs old lady brought by the family with
history of altered mental status and fever since
2 days.
Vitals :
• PR120; RR30; SpO2 85; BP 105/56
• T: 36.8
How would like to Proceed?

5. Airway :
• Patent , clear mouth
Breathing :
• RR 35, SpO2 85%
• Rt lower chest bilateral
course crepitation
Circulation:
• BP 105/55; PR 120; severely
dehydrated
• Peripheral sweaty and warm
extremities
• Peripheral pulses are all
palpable
Disability:
GCS:12 ( E4V4M4 )
Pupils : constricted ,equally
reactive
Reflu 14.5
Exposure:
No skin rashes
No signs of trauma , bruises

6. 53yrs old lady :
Confusion, headache
Fever : documented 38.5 , chills and rigor
Cough : productive of yellowish sputum, SOB
Vomiting >5 times, food content, no blood
Urine: dysuria
Past Medical History:
- Psychiatric disorder
- Diabetes Miletus
- HTN
Medication Hx : (not sure about it)
• Haloperidol 5mg BID
• Chloropomazine 100mg BID
• Valoprate Sodium 200mg BID
• Metformin 1g BID

7.  Confused , in distress
 Vitals same as previous
 Chest : same findings , SpO2 95%
 Abdomen : soft non tender
 CNS:
• GCS 12/15
• Pupils reactive equal
• normal reflexes in all limbs
• Power normal
• Toe down going
• No meningeal signs

8. VBG: normal pH, HCO3 and pCO2
Lactate: 4.2
Hb 11.3; WBC 8.7; ANC 7.8
CRP 51
eGFR: 68; Cr77; Ur 6.1
Na 140; K 4.3

10. Started on :
• Antibiotic cover , hydration , antipyretics
Impression:
• CAP
• UTI
• CNS infection
Referred to medicine.

11. Medical team Morning round, the plan was to
resume her regular medications
 Haloperidol 5mg BID.
 Chloropomazine 100mg BID.
 Valoprate Sodium 200mg BID.
 Metformin 1g BID.

12. • After 12 hours she was noted :
 More confused , sweaty
 Vitals : PR 120; T39.4 ; RR20
 Has upper limb cogwheel rigidity
• What is the cause of her new symptoms??

13. Sepsis:
• Pneumonia
• UTI
• CNS infection: viral encephalitis
Stroke
Neuroleptic Malignant Syndrome NMS

15.  A rare but potentially fatal idiosyncratic complication of
anti-psychotic drug therapy
 Occur usually due to:
• Initiation of new antipsychotic
• Increase dose of antipsychotic
 Both typical and atypical Antipsychotic can cause NMS
 Onset – from hours to days.
• 16% : within 24hrs.
• 66% : within 1 week.
• Virtually all cases : within 30 days.

16. • >38 C (100.4 F)Fever
• “Lead pipe” in most severe form
Muscle
rigidity
• Drowsiness, agitation, confusion, delirium,
coma
Altered
mental status
• Fluctuations in BP, tachypnoea, tachycardia,
sialorrhoea, diaphoresis, flushing, skin pallor,
incontinence
Autonomic
instability

18. • Agitation
• Dehydration
• Catatonia
• Iron deficiency
• Prior episode of NMS :20%
• external heat load
 Antipsychotic related Risk factors:
• Typical > atypical antipsychotic
• IV> PO
• High dose> low dose

22.  FBC – Leucocytosis (WBC 10000-40000)
 CK – elevated (> 1000 IU/L)
 Urine analysis – myoglobinuria indicate poor prognosis.
 ABG – Metabolic acidosis
 Serum iron – reduced ( ? An acute phase response)
 Serum catecholamine - elevated
 CSF – 95% normal.
 Brain imaging – usually normal.
 EEG – generalized slowing.(metabolic encephalopathy)

23.  Immediate withdrawal of the offending agent.
 Reinstitution of abruptly withdrawn dopaminergic
agents.
 Supportive care – mainstay of management
• Aggressive fluid resuscitation
• Monitoring and correction of electrolyte imbalances.
• Cooling measures (eg: cooling blankets, ice packs) – in
extreme hyperthermia.
• Dialysis – renal failure
• Ventilator support – respiratory failure

24. Benzodiazepine:
• Indications:
 Agitation, psychomotor hyperactivity, and muscle rigidity

• Lorazepam:
• Starting dose 1-2mg IM/IV every 3 minutes, until
muscle rigidity improves.
• Refractory cases or cases at risk for aspiration:
 RSI and NMB agents with a nondepolarizing agent (e.g.,
rocuronium and vecuronium)

25.  Dopaminergic agents
 Bromocriptine
 Dopamine agonist
 Starting dose - 2.5mg BID oral/NG
 Increase dose by 2.5mg every 24hrs.
 Max. dose – 45mg/day
 Amantadine
 200-400mg/day in divided doses oral/NG
 Dantrolene:
• Inhibits the release of calcium from the sarcoplasmic reticulum
• has no proven benefit.

26. ECT
• can be effective in,
 Poor response to supportive care and pharmacological
management.
 When idiopathic malignant catatonia cannot be
excluded.
 Persistent residual catatonia and parkinsonism after the
resolution of acute symptoms.

27.  Estimated risk of 30% of developing NMS
again with re-introduction of antipsychotics.
 Precautions:
• At least 2 weeks should be allowed from recovery
before re-challenge.
• Low potency conventional antipsychotics/ atypical
antipsychotics.
• Start with a low dose and titrate gradually.
• Careful monitoring for early signs of NMS.

28. Aka neuroleptics
atypical antipsychotics are as effective as
typical antipsychotics but have better side
effect profile
Route:
• PO; short-acting or long-acting depot IM
injections; sublingual

32. Conservative use of antipsychotics.
Reduction of risk factors.
Early diagnosis.
Prompt discontinuation of offending agents.
Early supportive care and medical
management.

33. Tintinalli’s EM
Rosen’s 8th edition
Toronto Notes
Medscape