neuroleptic malignant syndrome
DESCRIPTION
Neuroleptic Malignant Syndrome. Recognition, Risk factors and Management. Pathophysiology. Relative lack of dopamine dopamine receptor blockade inadequate dopamine production. Pathophysiology. Supporting evidence neuroleptic drugs block dopamine receptors - PowerPoint PPT PresentationTRANSCRIPT
Clinical Toxicology & Pharmacology, Newcastle Mater Misericordiae Hospital
Neuroleptic Malignant Neuroleptic Malignant SyndromeSyndrome
Recognition, Risk factors and Management
Clinical Toxicology & Pharmacology, Newcastle Mater Misericordiae Hospital
PathophysiologyPathophysiology
Relative lack of dopamine– dopamine receptor blockade– inadequate dopamine production
Clinical Toxicology & Pharmacology, Newcastle Mater Misericordiae Hospital
PathophysiologyPathophysiology
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 featuresClinical 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 featuresClinical features
Major (all within 24 h)– fever > 37.5oC (no other cause)– autonomic dysfunction– extrapyramidal features
Clinical Toxicology & Pharmacology, Newcastle Mater Misericordiae Hospital
Autonomic dysfunctionAutonomic 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 featuresExtrapyramidal 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 featuresMinor 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 factorsRisk factors
Incidence 1% (0.02–3.23) Pre-NMS
– psychomotor agitation– dehydration
Clinical Toxicology & Pharmacology, Newcastle Mater Misericordiae Hospital
Risk factorsRisk 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
ManagementManagement
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 therapyDrug 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 therapyOther 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