eMedicine Specialties > Pediatrics: Cardiac Disease and Critical Care Medicine > Critical Care
Neuroleptic Malignant Syndrome: Treatment & Medication
Updated: Dec 9, 2008
- Overview
- Differential Diagnoses & Workup
- Treatment & Medication
- Follow-up
Treatment
Medical Care
Neuroleptic malignant syndrome (NMS) is a life-threatening medical emergency that requires monitoring and management in an ICU. Tailor intervention levels to the severity of illness.
- Terminate the dopamine antagonist by withdrawing neuroleptic and neuroleptic malignant syndrome–potentiating drugs (eg, anticholinergics, lithium).
- Supportive measures include the following:
- Reduce body temperature using antipyretics, evaporative cooling, ice packs, and cooled intravenous (IV) fluids.
- Treat suspected or secondary infections with empiric antibiotics.
- Consider prophylactic intubation for patients with excessive salivation, swallowing dysfunction, coma, hypoxemia, acidosis, and severe rigidity with hyperthermia.
- Maintain pulmonary, cardiovascular, and renal functions by monitoring and managing such complications as respiratory failure, renal failure, disseminated intravascular coagulation (DIC), and arrhythmias.
- Sedate the patient.
- Specific measures include the following:
- A goal is rapid peripheral muscle relaxation. Rapid control of rigidity averts hyperthermia, rhabdomyolysis, renal failure, pneumonia, respiratory failure, DIC, and cardiovascular collapse.
- Considering all the disadvantages of dantrolene (vide infra), using nondepolarizing neuromuscular blocking agents (eg, pancuronium, other newer agents) is reasonable, along with such sedatives as benzodiazepines, to achieve rapid, predictable, and effective control of rigidity and hyperthermia.
- Dantrolene sodium directly relaxes muscles by inhibiting calcium release from the sarcoplasmic reticulum. Its disadvantages include the following: the mean response time is 1.7 days; rigidity and temperature reduction takes longer, effects are erratic, and effects are often incomplete; and dantrolene is a potentially hepatotoxic agent. Because of rigidity relieving action, it may offer another therapeutic modality for treatment of neuroleptic malignant syndrome (NMS).
- Bromocriptine is a dopamine agonist that overcomes neuroleptic-induced dopaminergic blockade. It has also been used in combination with dantrolene.
- Other agents that have been tried include amantadine, which enhances presynaptic release of dopamine, and levodopa/carbidopa, which increase presynaptic dopamine stores.
- Antimuscarinic agents are not recommended because they are not only ineffective but also may worsen hyperthermia.
- Consider electroconvulsive therapy (ECT). In 1987, Addonizio and Susman recommended ECT for persistently psychotic and agitated patients in whom distinguishing between neuroleptic malignant syndrome and lethal catatonia is difficult and in patients who run the risk of neuroleptic malignant syndrome recurring when neuroleptics are restarted.2
Consultations
- Consultation with a psychiatrist may be prudent as the patient is stabilized in the ICU and for further follow-up care after the patient is discharged from the ICU.
Medication
Skeletal muscle relaxants, nonparalytic
This agent is a direct muscle relaxant to control rigidity.
Dantrolene sodium (Dantrium)
Interferes with release of calcium from sarcoplasmic reticulum, thus directly inhibiting muscle contraction. Also prevents or reduces increase in myoplasmic calcium ion concentration that activates acute catabolic process associated with malignant hyperthermia. Available as sodium salt in 25-mg, 50-mg, and 100-mg caps and in 20-mg vial for IV administration.
Adult
Spasticity: 25 mg/d PO initially, gradually increase to tid/qid; then increase dose by 25 mg q4-7d; not to exceed 100 mg 2-4 times/d or 400 mg/d
Hyperthermia:
Preoperative prophylaxis: 4-8 mg/kg/d PO divided qid administered 1-2 d before surgery for patients at risk; to prevent recurrence, administer last dose 3-4 h before scheduled surgery; alternatively, 2.5 mg/kg IV infused over 1 h before anesthesia; additional doses may be needed during surgery, especially if prolonged
Crisis : 1 mg/kg IV, may repeat prn; not to exceed a cumulative dose of 10 mg/kg; if physiologic and metabolic abnormalities reappear, repeat regimen
Postcrisis follow-up: 4-8 mg/kg/d PO divided qid for 1-3 d; administer IV when PO therapy is not practical; individualize dosage beginning with 1 mg/kg IV or more as clinical situation dictates
Pediatric
Spasticity: 0.5 mg/kg PO bid initially, increase frequency to tid/qid at 4-d to 7-d intervals; then increase dose by 0.5 mg/kg increments; not to exceed 3 mg/kg 2-4 times/d up to 400 mg/d
Hyperthermia: Administer as in adults
Use with verapamil may result in hyperkalemia and myocardial depression; concomitant use of estrogen increases risk of hepatotoxicity; CNS depression is exaggerated when used with CNS depressants; incompatible when mixed with dextrose, saline, or bacteriostatic water solutions
Documented hypersensitivity; active hepatic disease (eg, hepatitis, cirrhosis)
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Caution with impaired cardiac or pulmonary function or history of previous liver disease; may cause hepatotoxicity (more common in females or patients >35 y), onset of overt hepatitis typically 3-12 mo after treatment initiation; monitor baseline and periodic liver function; adverse reactions include hepatitis, drowsiness, seizures, dizziness, lightheadedness, confusion, headaches, pleural effusion with pericarditis, tachycardia, hematuria, diarrhea, nausea, vomiting, GI bleeding, severe constipation, dysphagia, rash, photosensitization, acnelike rash, pruritus, urticaria, and abnormal hair growth; avoid alcohol and unnecessary exposure to sunlight; causes drowsiness; may impair ability to perform hazardous functions requiring mental alertness or physical coordination; protect IV from light; use reconstituted injection within 6 h; precipitant forms when IV placed in glass containers
Dopamine agonists
For a dopamine agonist to offer clinical benefit, it must stimulate D2 receptors. D2 receptor blockade might cause neuromalignant malignant syndrome by removing tonic inhibition from the sympathetic nervous system or more directly by neuroleptic agents (eg, phenothiazines).
Bromocriptine (Parlodel)
Is an ergot alkaloid with dopamine receptor agonist action.
Adult
10 mg PO tid initially; if no improvement in 24 h, may increase dose; not to exceed 20 mg PO qid
Pediatric
Limited data available; 1.25 mg PO q12h initially, may gradually increase dose prn; not to exceed 20 mg/d
Toxicity may increase with ergot alkaloids; amitriptyline, butyrophenones, imipramine, methyldopa, phenothiazines, and reserpine may decrease bromocriptine effects
Documented hypersensitivity; ischemic heart disease; peripheral vascular disorders
Pregnancy
B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
Precautions
May worsen condition of patient with psychiatric illness, peptic ulcer disease, or preexisting peripheral vascular disease; may result in cardiac decompensation in patients with history of myocardial infarction; adverse reactions include orthostatic hypotension, hallucinations, confusion, delirium, nausea, and vomiting
Amantadine (Symmetrel)
Has been tried in NMS because it increases synaptic dopamine activity. As an antiviral, actions include inhibition of influenza A virus uncoating, prevention of virus penetration into host, and inhibition of M2 protein in the assembly of progeny virions. Exhibits antiparkinsonian activity by blocking reuptake of dopamine into presynaptic neurons and by causing direct stimulation of postsynaptic receptors.
Adult
Data limited; several case reports describe using 100 mg PO bid
Pediatric
Not established; 5 mg/kg/d PO qd or divided bid has been used for influenza A prophylaxis; not to exceed 150 mg/d (age 1-9 y) or 200 mg/d (age >10 y)
Drugs with anticholinergic or CNS stimulant activity increase amantadine toxicity; the concurrent administration of hydrochlorothiazide plus triamterene with amantadine may increase plasma concentrations of amantadine
Documented hypersensitivity
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Caution with liver disease, epilepsy, history of recurrent eczematoid dermatitis, or uncontrolled psychosis; may increase seizure activity or EEG disturbances with preexisting seizure disorders; decrease dosage with renal impairment and with active seizure disorders; adverse reactions include orthostatic hypotension, edema, dizziness, confusion, insomnia, difficulty in concentration, restlessness, hallucinations, seizures, livido reticularis, nausea, vomiting, xerostomia, and urinary retention; avoid alcohol; may cause drowsiness; may impair ability to perform activities requiring mental alertness or coordination; do not abruptly discontinue therapy because may precipitate a parkinsonian crisis
Levodopa and carbidopa (Sinemet)
Levodopa is a metabolic precursor of dopamine. Few reports of its use in combination with carbidopa (vide infra) in NMS exist because of its dopaminergic action. Crosses the blood-brain barrier and is converted to dopamine by enzyme action, thus restoring dopamine levels in the extrapyramidal centers such as substantia nigra.
Carbidopa, a dopamine decarboxylase inhibitor, does not cross the blood-brain barrier. Diminishes the metabolism of levodopa in the GI tract and peripheral tissues, thus increasing levodopa's availability in the CNS and enhancing its effectiveness.
A variety of dosage ratios are available (ie, 1:10 carbidopa to levodopa, 1:4 carbidopa to levodopa). Also available as IR and SR dosage forms.
Adult
25 (carbidopa)/250 (levodopa) mg PO tid/qid
Alternatively, 500-1000 (based on levodopa component) mg/d PO divided q6-12h; increase by 100-750 mg/d q3-7d until response; not to exceed 8000 mg/d
Pediatric
Not established
Antacids increase bioavailability of levodopa; benzodiazepines, hydantoins, methionine, papaverine, and pyridoxine decrease levodopa effectiveness; iron salts and anticholinergics decrease GI absorption of levodopa; MAOIs may increase hypertensive reaction; may decrease metoclopramide effects; methyldopa may have additive hypotensive effects
Documented hypersensitivity; narrow-angle glaucoma; malignant melanoma; undiagnosed skin lesions
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Caution with severe cardiovascular or pulmonary disease, asthma, occlusive cerebrovascular disease, renal or hepatic or endocrine disease, affective disorders, major psychoses, cardiac arrhythmias, and chronic wide-angle glaucoma
More on Neuroleptic Malignant Syndrome |
| Overview: Neuroleptic Malignant Syndrome |
| Differential Diagnoses & Workup: Neuroleptic Malignant Syndrome |
 Treatment & Medication: Neuroleptic Malignant Syndrome |
| Follow-up: Neuroleptic Malignant Syndrome |
| References |
| « Previous Page | Next Page » |
References
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Further Reading
Keywords
neuroleptic malignant syndrome, NMS, neuroleptics, antidopaminergic activity, serotonin, schizophrenia, respiratory failure, cardiovascular collapse, renal failure, arrhythmias, thromboembolism, hypoxia, ischemic encephalopathy, urinary incontinence, diaphoresis, sialorrhea, hypertension, respiratory distress, dehydration, hypotension, butyrophenones, haloperidol, phenothiazines, thioxanthenes, long-acting neuroleptics, benzamines, tricyclic antidepressants, monoamine oxidase inhibitors, MAOIs, anticonvulsants, lithium, domatine antagonists
