Download Neuroleptic Malignant Syndrome

Neuroleptic Malignant
Syndrome
Recognition, Risk factors and
Management
Clinical Toxicology & Pharmacology, Newcastle Mater Misericordiae Hospital
Pathophysiology

Relative lack of dopamine
– dopamine receptor blockade
– inadequate dopamine production
Clinical Toxicology & Pharmacology, Newcastle Mater Misericordiae Hospital
Pathophysiology

Supporting evidence
– neuroleptic drugs block dopamine
receptors
– occurs with other dopamine blocking
drugs
– occurs on sudden withdrawal of
antiparkinsonian therapy
– responds to dopamine agonists
Clinical Toxicology & Pharmacology, Newcastle Mater Misericordiae Hospital
Clinical features

Essential
– recent or current therapy with dopamine
blocking drug
neuroleptic
 other drug eg metoclopramide

– recently stopped a dopamine agonist eg
L-dopa
Clinical Toxicology & Pharmacology, Newcastle Mater Misericordiae Hospital
Clinical features

Major (all within 24 h)
– fever > 37.5oC (no other cause)
– autonomic dysfunction
– extrapyramidal features
Clinical Toxicology & Pharmacology, Newcastle Mater Misericordiae Hospital
Autonomic dysfunction

2 or more of
– hypertension or labile BP
systolic > 30 mmHg above baseline or
 diastolic > 20 mmHg above baseline
 variability of > 30 mmHg systolic or >20 mmHg diastolic
between readings

–
–
–
–
tachycardia (pulse > 30 bpm above baseline)
diaphoresis (intense)
incontinence
tachypnoea (> 25 breaths/min)
Clinical Toxicology & Pharmacology, Newcastle Mater Misericordiae Hospital
Extrapyramidal features

2 or more of
–
–
–
–
–
–
bradykinesia
lead-pipe or cogwheel rigidity
resting tremor
sialorrhoea
dysphagia
dysarthria/mutism
Clinical Toxicology & Pharmacology, Newcastle Mater Misericordiae Hospital
Minor features

Support but are not required for
diagnosis
–
–
–
–

rise in creatinine kinase
altered sensorium/delirium
leucocytosis > 15,000x109/L
low serum iron
Help confirm diagnosis
– therapeutic response to dopamine agonist
Clinical Toxicology & Pharmacology, Newcastle Mater Misericordiae Hospital
Risk factors


Incidence 1% (0.02–3.23)
Pre-NMS
– psychomotor agitation
– dehydration
Clinical Toxicology & Pharmacology, Newcastle Mater Misericordiae Hospital
Risk factors

Related to treatment
– neuroleptic dose in first 24h > 600 mg of
chlorpromazine
– maximum dose in any 24h > 600 mg of
chlorpromazine
– required restraint or seclusion

Associated
– past ECT
Clinical Toxicology & Pharmacology, Newcastle Mater Misericordiae Hospital
Management

High risk patients
– monitor temperature tds
– monitor blood pressure tds
– record episodes of diaphoresis

On suspicion
– assess for other medical illness
– FBC, MBA, CK, serum iron

On diagnosis
– withdraw all dopamine blocking drugs
Clinical Toxicology & Pharmacology, Newcastle Mater Misericordiae Hospital
Drug therapy

Bromocriptine
– 2.5 mg q8h up to 5 mg q4h
– continue for 7–10 days after resolution
then taper over 1–2 weeks (except depot
preparations)

Dantrolene
– 2–3 mg/kg
– extreme rigidity, very high fever (>
40oC), unable to tolerate oral treatment
Clinical Toxicology & Pharmacology, Newcastle Mater Misericordiae Hospital
Other therapy

Benzodiazepines
– to control agitation/delirium

ECT
– refractory to adequate trial of dopamine
agonist/supportive care
– after resolution of acute features
remain catatonic or
 develop ECT-responsive psychotic features

– suspected acute lethal catatonia
Clinical Toxicology & Pharmacology, Newcastle Mater Misericordiae Hospital