Neuroleptic malignant syndrome

Question 1

Define neuroleptic malignant syndrome.

Answer 1

Acute potentially life threatening complication or antipsychotic/dopamine antagonist treatment or acute withdrawal of it

A disorder of thermoregulation and neuromotor control

Question 2

How common is NMS?

Answer 2

<1% of patients taking antipsychotics affected

Has declined over last 20yrs which may be due to greater awareness or more second-generation antipsychotic use

Question 3

What is the pathophysiology of NMS?

Answer 3

Not well established - acute imbalance or dysregulation of CNS neurotransmitters is strongly suspected

Question 4

What are the risk factors for NMS?

Answer 4

• High dose typical antipsychotics - usually within 3-9 days of starting treatment; has been reported with antidepressants but less common
• Rapid dose changes or withdrawal
• Male gender
• Older age
• Pre-existing brain abnormality e.g. dementia, trauma, Wilson’s, PD.
• Dehydration

Question 5

What are the clinical features of NMS?

Answer 5

• Muscle rigidity
• Hyperthermia
• Hyporeflexia
• Diaphoresis, urinary incontinence
• Autonomic dysregulation e.g. tachycardia, hypotension
• Altered consciousness - confusion, delirium, stupor
• Hypermetabolism

Question 6

How do you diagnose NMS?

Answer 6

• Raised CK - typically >1000
• Raised WCC
• Deranged LFTs - may get liver failure
• Deranged renal function (due to rhabdo from raised CK) - e.g. myoglobinuria, hyperkalaemia, hyper/hyponatraemia

Other:
* ECG - long PR, QRS, QT; ST or T wave abnormalities
* CT scan - exclude brain abnormality
* Urine/blood culture
* CXR - increased risk of aspiration

Question 7

What is the management of NMS?

Answer 7

• Stop causative agent + transfer to ITU
• Support care:
• Fluids - treat the rhabdomyolysis, consider urine alkalinisation
• Cooling - treat hyperthermia
• Sedation with benzodiazepines - relax muscles and manage agitation
• Bromocriptine (DA) or Dantrolene - muscle relaxant if no response to supportive treatment to treat hyperthermia and rigidity

Other:
* ECT - case reports; may further elevate CK

Question 8

When can antipsychotics be started again after NMS?

Answer 8

Wait at least 2 weeks after NMS

Question 9

What are some signs of severe NMS requiring critical care?

Answer 9

Moderate/severe NMS
Severe hyperthermia >38.5C despite cooling
Coma
Compromised ventilation
Acute renal failure or severe hyperkalaemia

Question 10

What is the classification of severity of NMS?

Answer 10

Question 11

What are the complications of NMS?

Answer 11

• Sepsis
• AKI
• Status epilepticus
• Rhabdomyolysis
• PE - due to immobility
• Aspiration
• Cognitive deficits
• Worsening psychosis

Question 12

What is the prognosis with NMS?

Answer 12

Mortality varies - studies report 8-9%
Recurrence is as high as 30%