Neuroleptic Malignant Syndrome

Definition

Neuroleptic malignant syndrome (NMS) refers to the combination of hyperthermia, rigidity, and autonomic dysregulation that can occur as a serious complication of the use of antipsychotic drugs. Rare, but potentially life threatening complication of neuroleptics treatment. (Medscape) Refers to combination of

Hyperthermia

Severe muscular rigidity

Autonomic dysregulation

Epidemiology

0.5 1.0 % who exposed to anti-psychotic Most frequently with high potency compounds eg. Haloperidol and fluphenazine 90% developed within the first 10 days of treatment More common in males, younger than 40

Mortality rate : 15 25 %, even higher when depot antipsychotic get involved.

Pathophysiology

Unknown Believed to be result from excessively rapid blockade of post synaptic dopamine receptors

Include abnormalities of :

Centre dopamine system Muscle membrane dysfunction Sympathetic nervous system

Evolve over 24-72 hours and if untreated can last until 10-14 days
Diagnosis often missed at early stages and withdrawal or agitation may mistakenly be considered to reflect an exarcebation of psychosis.

Risk Factors

Medication factors:
High dose of high potency antipsychotics Rapid increase of antipsychotic dosage

Patient factors:

Concurrent illness Dehydration Exhaustion Poor nutrition External heat load Male & younger age

Clinical Features(FLATER)
Fever Leukocytosis Autonomic instability (sweating, increase BP n PR) Tremor Elevated enzymes (creatinine phosphokinase d/t rhabomyolysis) Rigidity of muslce (lead pipe)

Diagnosis DSM-IV criteria

Development of severe muscle rigidity and elevated temperature associated with use of neuroleptic medication Two (or more) of the following:

Diaphoresis Dysphagia Tremor

Incontinence
Changes in level of consciousness ranging from confusion to coma Mutism Tachycardia Elevated or labile blood pressure Leucocytosis Laboratory evidence of muscle injury. (e.g., elevated CPK)

Laboratory Investigations

Full blood count Blood urea & serum electrolytes Liver function test Creatine kinase level Urinalysis urine myoglobin Blood & urine culture for fever workup

Expected result in NMS

Increase WBC Increase creatinine phosphokinase Increase liver enzyme Increase myoglobin- renal failure

Management

Stop all neuroleptics Monitor vital signs and renal function Correct volume depletion, hypotension with intravenous fluid Methods to reduce temperature

Cooling blanket Antipyretics

Cooled IV fluids
Ice packs

Drug therapy

Dopamine agonists
Bromocriptine

2.5mg TDS (max: 60mg) Relieve akinesia, rigidity, tremor

Skeletal muscle relaxants

Dantrolene,

2-3mg/kg divided TDS up to 10mg/kg/day Treat NMS associated muscular rigidity