Transcript Slide 1

Neuroleptic Malignant
Syndrome (NMS)
Sue Henderson
Definition
• Rare adverse reaction to dopamine
receptor antagonists (blockers)
• Leading to autonomic dysfunction
• Can be fatal if not recognized early
Commonly associated with:
• haloperidol (Serenace)
• fluphenazine (Prolixin)
• chlorpromazine (Largactil)
Less commonly associated with:
atypicals:
• quetiapine (Seroquel)
• risperidone (Risperdal)
• olanzapine (Zyprexa)
dopamine receptor antagonists:
• prochlorperazine (Stemetil)
• metoclopramide (Maxalon)
• promethazine (Phenergan)
Pathophysiology
• Not fully understood
• Probably dopaminergic blockade or
depletion in CNS
• May be a drug induced malignant
catatonia (? same underlying
pathophysiology) (Fink, 1996, as cited in Strawn, Keck & Caroff, 2007).
• Genetics may be involved
Incidence
• 0.5% to 3% of all patients treated with
traditional antipsychotics
• Recent 0.01% to 0.02% (Stubner, 2004, as cited in Strawn, Keck &
Caroff, 2007). (? Due to atypical use)
• Haloperidol implicated in ½ cases
(potency, widespread use)
Death in 10% of cases (Strawn, Keck & Caroff, 2007).
Risk Factors
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previous history of NMS/EPSE
dehydration
discontinuation of antiparkinsonian
withdrawal of benzodiazepines
history of organic brain syndrome
use of high potency agents
iron deficiency
Onset
At any time - can develop rapidly
Most cases when:
• drug started
• dosage increased
• rapidly titrated
Mild to severe - depending on individual
Clinical manifestations
Sudden change in mental status
Muscle
rigidity
Fever
Sudden change in mental status
Mental state changes precede other signs in
80% of cases
Clouding of consciousness ranging from:
• confusion to stupor or coma
• agitation,
• delirium, and
• catatonia
Fever
• Hyperpyrexia > 38 °C of unknown origin
(? caused by dopamine blockade in
hypothalamus causing temperature
dysregulation and profuse sweating)
Muscle Rigidity
• Dystonia abrupt onset stiffening and
rigidity in large muscles (especially head &
neck)
• Severe muscle rigidity produces excess
body heat contributing to hyperpyrexia
• Sometimes difficulty swallowing or a
sensation of tongue thickening that rapidly
worsens
Rigidity
As the syndrome progresses:
• increasing muscle rigidity can lead to diminished
chest wall compliance, hypoventilation, and
even respiratory failure.
Other
• EPSEs: parkinsonian tremors, akathisia
• elevated or labile blood pressure
• tachycardia, tachypnea, tremor, and urinary
incontinence
Laboratory
• Raised Creatine kinase (muscle enzyme)
• Raise Myoglobinuria (muscle protein)
• Creatine kinase rises 2 – 4 hours after muscle
injury (indicator degree muscle damage),
continued rise may indicate onset :
• Rhabdomyolysis (skeletal muscle break down)
releases myoglobin into circulation.
• Once myoglobin in kidneys, it precipitates in renal
tubules causing kidney damage and subsequent
renal failure.
Lab: other
• proteinuria secondary to stress/tissue
damage
• elevated white blood cell count
• Arterial blood gas analysis - assess for
adequate oxygenation and metabolic
acidosis (Harrison & McErlane, 2008).
Prevention
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Conservative use of antipsychotics
Reduction of risk factors
Early diagnosis
Prompt discontinuation of offending
medications
Medical Management
Depending on symptom severity and
complications:
• See table in handout (Woodbury & Woodbury, 1992 cited in Strawn,
Keck & Caroff, 2007).
• See video Brvar and Bunc (2007) pre and
post Dantrolene
Re-challenge Anti-psychotics
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30% risk of developing again
Check reports on previous episodes for accuracy
Clearly documented indications for antipsychotics
Consider alternative medications
Reduce risk factors
Rechallenge at least 2/52 after recovery from NMS
Use low doses of low-potency conventional
antipsychotics or atypical antipsychotics
• Titrate gradually after a test dose
• Monitor for early signs of NMS
• Obtain informed consent from patients/family regarding
benefits of antipsychotic versus risk recurrence (Strawn, Keck,
& Caroff, 2007).
Resources
Neuroleptic Malignant Syndrome Information
Service
www.nmsis.org
References
Brvar, M., & Bunc, M. (2007). Video of dantrolene
effectiveness on neuroleptic malignant syndrome
associated muscular rigidity and tremor. Critical Care
11(3), 415.
Fink, M. (1996). Neuroleptic malignant syndrome and
catatonia: One entity or two? . Biological Psychiatry, 39,
1-4.
Harrison, P. A., & McErlane, K. S. (2008 ). Neuroleptic
malignant syndrome American Journal of Nursing,
108(7), 35-38.
Strawn, J. R., Keck, P. E., & Caroff, S. N. (2007).
Neuroleptic malignant syndrome. American Journal of
Psychiatry, 164(6), 870-876.