COALINGA STATE HOSPITAL. Effective Date: August 31, 2006

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COALINGA STATE HOSPITAL NURSING POLICY AND PROCEDURE MANUAL SECTION Emergency Procedures POLICY NUMBER: 717 Effective Date: August 31, 2006 SUBJECT: NEUROLEPTIC MALIGNANT SYNDROME 1. PURPOSE: To provide nursing staff with appropriate guidelines and procedures for recognition of and treatment of Neuroleptic Malignant Syndrome (NMS). 2. POLICY: All individuals who exhibit Neuroleptic Malignant Syndrome symptoms shall receive individualized, appropriate treatment to alleviate those symptoms. 3. DEFINITION: Neuroleptic malignant syndrome (NMS) is a drug-induced disorder, characterized by disturbances in mental status, temperature regulation, and autonomic and extrapyramidal functions. It is a rare, but life-threatening disorder associated with the use of antipsychotic medications and other medications with similar pharmacologic properties. Fever, muscular rigidity, altered mental status, and autonomic dysfunction characterizes the syndrome. 4. GENDERAL INFORMATION: Although potent neuroleptics (e.g. haloperidol, fluphenazine) are more frequently associated with NMS, all antipsychotic agents, typical or atypical, may precipitate the syndrome [e.g. prochlorperazine (Compazine), promethazine (Phenergan), clozapine (Clozaril), risperidone (Risperdal). NMS has also been associated with non-neuroleptic agents that block central dopamine pathways [e.g. metoclopramide (Reglan), amoxapine (Ascendin), Lithium]. Often misdiagnosed, NMS is easily confused with other health problems; Malignant Hyperthermia; Heat Stroke; Lethal Cataonia; Hyperthermic Syndromes associated with other pharmacologic agent; viral encephalitis; structural brain lesions, and basal ganglia disorders with rigidity. NMS primarily occurs following the use of antipsychotic drugs, most commonly haloperidol and depot agents such as fluhenzine deconate -1-

(prolixin-d). However, other antipsychotic agents such as chloropromazine (thorazine), thiothixene, (navane), & thioridazine (melleril) have also been implicated as causative agents. NMS occurs in 0.5% to 1.5% of individuals using antipsychotic drugs. In some instances hot weather may trigger episodes of NMS, but it occurs throughout the seasons. Antipsychotics act primarily by blocking the neurotransmitter, dopamine, at specific receptor sites in the brain. It is hypothezied that this blockade can cause NMS. Dopamine is thought to play an important role in motor function, emotional reaction, and thought processes. The association of hyperthermia and hyperadrenegic function suggests involvement of hypothalamic dopaminergic tracts regulation temperature. It is reported that over half the cases of NMS involve the concomitant drug treatment with other than antipsychotics (e.g. lithium carbonate, tricylic antidepressants, antiparkinsonian, and benzodiazepines). Mortality/Morbidity: Due to increased awareness of this syndrome and efforts at prevention the incidenceis probably less now than in the past. The incidence of mortality, once reported at 20 to 30% is not estimated at 5 to 11.6%. Death usually results from respiratory failure, cardiovascular collapse, myoglobinuric renal failure, or arrhythmias. Morbidity from NMS includes rhabdomyolysis, pneumonia, renal failure, seizures, arrhythmia s, and respiratory failure. Sex: NMS has been reported to be more common in males (2:1 ration of males to females), most likely because of increased use of neuroleptics in males. Age: There is no age prediction for NMS. It may occur in individuals at any age that are receiving neuroleptics or other precipitation medications. 5. ASSESSMENT: ASSESMENT OF THE AIRWAY, BREATHING, AND CIRCULATION (ABC S) CLINICAL MANIFESTATIONS: NMS is more likely to develop following initiation of neuroleptic therapy or an increase in dose. The onset can be within hours, but on average, it is 4-12 days after beginning therapy. -2-

However, NMS can occur at anytime during neuroleptic use, even years after initiating therapy. Of those individuals who develop NMS, 90% of them will do so within 10 days. Some reports indicate that at anytime during drug use elevated blood pressure may precede the syndrome by a few days and can progress rapidly in 24 to 72 hours to the full-blown episode. CLASSIC SYMPTOMS: NMS is diagnosed by the development of muscle rigidity and elevated temperature following administration of antipsychotic medication. (Individual presents in a hypothalamic or adrenergic crisis with evidence of increased metabolic utilization) Severe muscle rigidity (lead pipe presentation as opposed to cogwheeling) Fever (100.5 to 107.5 F) 2.3.1.16 Altered consciousness; Change in mental status Restlessness Delirium Stupor Coma 2.3.1.16.1 Autonomic dysfunction Unstable, labile pulse & pressure; Hypotension or hypertension (75/50 to 180/130 mm/hg) Tachycardia Profuse Diaphoresis Tachypnea (18 to 40 breaths/min) Incontinence Masked faces (individuals may be agitated, psychotic, & delirious) 2.3.1.16.2 Autonomic manifestations Parllor Flushing Urinary retention; incontinence 2.3.1.16.2.1 Other motor disturbances Parkinsonian-like syndromes (tremors, akinesia, dyshpagia, drooling, bradykinesia) -3-

Tremor Sialorrhea (excessive flow of saliva) Dystonic reactions Chorea Occulogyric crisis Dyskinesias Seizures 2.3.1.16.2.2 Neurological symptoms Dysphasia Aphonia Hyporflexia Extensor plantar responses Akinetic mutism Dysarthria Ataxia Posturing 2.3.1.16.2.3 Laboratory findings Elevated creatinine phosphokinase- the muscle enzyme (CPK: 240 to 14,3000 U/L) Leukocytosis (elevated white blood count) Metabolic acidosis Elevated liver function tests Generalized EEG abnormalities Different Diagnosis of Neuroleptic Malignant Syndrome Malignant Symptom NMS Hyperthermia Heatstroke Lethal Catatonia Hyperthermia Yes Yes Yes Yes Muscle Yes Yes Not typical Yes Rigidity Diaphoresis Yes Yes Not typical Yes Tachycardia Yes Yes Yes Yes Respirations Rapid Rapid Rapid N/A Blood Increased Increased Increased N/A Pressure Acidosis Yes Yes Yes? Coagulopathy Yes Yes Yes? Myoglobinuria Yes Yes Yes? Mental Status Impaired Impaired Impaired Impaired Precipitant Antipsychotics Halothane Exposure or? -4-

Anectine? Exercise Stress Elevated CPK Yes Yes N/A N/A Elevated LFT Yes N/A N/A N/A Leukocytosis Yes N/A Yes N/A Onset Hrs-Days Min-Hrs Min-Hrs Days-Weeks Mortality 10-20% 30% 20-50% 75-100% Therapy Dantrolene, Dopaminergic Agnoists Dantrolene? Dantrolene ECT, Corticosteroids 6. TREATMENT: Successful treatment requires prompt recognition, withdrawal of neuroleptic agent, exclusion of other medical conditions, aggressive supportive care, and administration of certain pharmacotherapies. It is essential to recognize signs of NMS early and discontinue antipsychotic medication when appropriate. Intensive medical nursing carae are important. Options vary, but dopamine agonsits (bromocriptine, amantadine), benzodiazepines, and dantrolene have been avocated as beneficial, particularly in sever cases. Immediate interventions include: immediate cessation of the antipsychotic & starting the individual on an anticholinergic medication such as diphenhydramine or benztropine. Supportive interventions include: IV hydration, cooling blankets, antipyretics, ice packs, evaporative cooling; if required-antipyretics & supplemental oxygen. A careful history should be taken before starting a new neuroleptic medication. Drug treatment which is recommended: Dantrolene- the drug of choice is peripheral skeletal muscle relaxant used to treat muscular rigidity. Dose ranging: IV 0.8 to 10mg/kg/day (exceeding 10mg/kg/day may lead to hepatic toxicity). Initial dose: 2 to 3 mg/kg/day over 10 to 15 min, P.O. range: 50 to 700 mg/kg/day given in divided doses of 100 to 200 mg. Parlodel (bromocriptine): given P.O., 2.5 mg to T.I.D. Meds which have been used with variable success are: Symmetrel (amantadine): P.O. 200 mg to 400 mg/day & Ativan (lorazepam): IV (2 mg) with repeated doses. Keep in mind that although individuals with NMS have recovered completely with conservative treatment alone, (cessation of antipsychotic & supportive measures), it is very difficult to assess the primary contribution to any given treatment when combined with all the conservative measures. -5-

7. IMPLEMENTAION AND INTERVENTION: NURSING ACTION A. Assess the individual s vital signs, including pain assessment, symptoms and precipitating history. B. Notify physician/mod/nod and RN immediately and report individual s status. C. Initiate emergency measures and supportive care (CPR, cooling measures, etc.). C. Hold next dose of antipsychotic medication until individual is examined by a physician. D. Continually monitor and document the individual s vital signs and symptoms. E. Continue supportive care. F. If Dantrolene is ordered, call pharmacy STAT. G. The individual must be monitored closely to rule out underlying infection. Adequate hydration must be maintained. KEY POINTS A. Use the DIFFERENTIAL DIAGNOSIS TABLE as a guide. C. If NMS is diagnosed, prepare to transfer individual to an acute medical facility where intensive monitoring and treatment is available. C. A physician s order is not required to hold a medication in an emergency. D. Use the Emergency Care Flow Sheet. F. During off duty hours Dantrolene can be obtained form the night locker by the NOD. 8. EVALUATION: Documentation should include: 1. All assessment data 2. the date, time, method of notification, and all findings that were relayed to the physician. 3. Arrival time of medical help 4. All interventions given 5. Client s response to treatment 6. Client s status and disposition at conclusion of interventions and follow up -6-

9. CLIENT EDUCATION: After an episode of NMS, the individual must be told that he/she is at risk for recurrence. The individual should report this reaction to all healthcare providers. CROSS REFERENCE: NP&P #700 Medical Emergency -7-