Abstract: Neuroleptic malignant syndrome (NMS) is a potentially lethal condition that has been described in patients with idiopathic Parkinson’s disease (PD) after long-term dopaminergic medications are suddenly stopped or moderately decreased. If patients with PD develop severe rigidity, stupor, and hyperthermia, L-Dopa withdrawal should be suspected and the dopaminergic drug restarted as soon as possible to prevent rhabdomyolysis and renal failure. Nurses who are knowledgeable about NMS can provide prompt identification of the PD patient’s condition and prevent a potentially lethal cascade of symptoms.
A 72-year-old white male diagnosed with Parkinson’s disease (PD) 14 years ago, presented to our clinic with a temperature of 102.5F, decreased mental status, rigidity, and stiffness. The patient’s wife reported that her husband’s freezing episodes had intensified over the past week and that his mental status had declined. His weakness and confusion caused him to spend the previous night on the bathroom floor. The fire department was called the next day to assist her in rifting him so she could transport him to the hospital. One month before this incident, the patient had a bilateral deep brain stimulator (DBS) placed into his basal ganglia to treat tremors and dyskinesias related to PD. The surgical hospital course had been unremarkable.
Physical Examination
The patient presented with altered mental status, inability to follow commands, hallucinations, confusion, and inability to ambulate or perform activities of daily living. His temperature was 102.5F, and his neck and extremities were rigid. There were resting pronation and supination tremors of both hands, with marked pill- rolling actions of the fingers. Mild to moderate dysarthria, hypophonia with a monotone voice, and hypomimia were observed. Surgical sites were healed without signs of infection. Blood pressure was normal to hypotensive, and the patient was tachycardie. The findings of the rest of the examination were unremarkable.
A neurologist reviewed preoperative and postoperative medications and discovered that the carbidopa/ levodopa 25 mg/100 mg dose had been reduced by tab every 3 hours after the DBS implant had been turned on and programmed according to presenting PD symptoms. Pramipexole was continued at 0.5 mg tid, and selegiline 5 mg qd had been discontinued.
Abnormal Diagnostic Tests/Results
The abnormal laboratory test results found at the time of admission gave an indication that immediate intervention was required (Table 1). A chest X ray revealed a few interstitial lung markings consistent with shallow inspiration, but were otherwise normal. A lumbar puncture was negative for infection, and an electrocardiogram revealed tachycardia. A magnetic resonance imaging (MRI) brain scan demonstrated normal brain parenchyma, evidence of metallic electrodes in the basal ganglia, and no evidence of acute abnormality. Cultures and sensitivities of blood, cerebrospinal fluid, sputum, and urine were obtained. The sputum culture revealed moderate Pseudomonas aeruginosa; the rest of the cultures remained negative for 72 hours. A large amount of blood and protein, without bacteria, was noted in the urine specimen. Because of the uncertainty of the diagnosis, tests also were obtained for fecal leukocytes, St. Louis encephalitis IgM, and West Nile virus IgM; all these tests were negative. The admitting diagnosis was possible pneumonia, rhabdomyolysis, and urinary tract infection. By the second day of his hospitalization, the patient’s condition met the diagnostic criteria for neuroleptic malignant syndrome (NMS) secondary to dopamine withdrawal.
A definite diagnosis of NMS requires both essential features and associated symptoms, which are listed in the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV, American Psychiatric Association, 2000). The essential symptoms exhibited by the patient that allowed for this diagnosis were hyperthermia and severe muscle rigidity. His associated symptoms included changes in level of consciousness, leukocytosis, tachycardia, diaphoresis, incontinence, and laboratory evidence of muscle injury in the form of extreme elevations of creatine kinase (CK) levels (12,542 U/L) (Nicholson & Chiu, 2004).
Major Nursing Issues
This patient’s major nursing issues were hyperthermia, possible dehydration, stiffness and rigidity, and altered mental status. All of these conditions rendered him unable to perform his activities of daily living. Nurses played a major role in providing supportive care, including adequate hydration, proper nutrition, and fever reduction.
Table 1. Laboratory Tests on Admission
Table 2. Laboratory Tests on Hospital Day 7
The patient’s presenting symptoms and abnormal laboratory values provided nurses with clinical information that required them to take action before a diagnosis was made by the neurologist. The 102.5F fever was critical and predisposed this patient to seizures and further dehydration. The nurse administered antipyretics for hyperthermia and intravenous (IV) fluids. Dantrolene sodium (Dantrium) was ordered as a direct-action muscle relaxant. This drug acts directly on skeletal muscle to interfere with intracellular calcium movement. By blocking the calcium release from the muscle, the activation of acute catabolism associated with neuroleptic malignant syndrome is halted, thus reducing the risk of rhabdomyolysis (Maloni & Ross, 2004). Anticoagulant therapy, such as heparin, may be ordered to prevent disseminated intravascular coagulation (DIC).
Comfort measures for the patient included tepid sponge baths and placement on a temperature-regulating blanket to decrease temperature elevations. Due to abnormalities in his chest X ray and arterial blood gas (ABG) analysis, this patient needed to cough and deep-breathe several times every hour to clear secretions that cause pneumonia. He also needed oxygen by nasal cannula at 2-3 liters to increase his blood oxygen level and promote bronchodilation; this oxygenation also improved his mental status. Antibiotics were administered as ordered.
The elevated blood urea nitrogen (BUN) indicated that he probably was dehydrated. Although the BUN is directly related to the metabolic function of the liver, it also represents the excretory function of the kidney. The nurse placed a urinary catheter to monitor his urine output, expecting at least 30 cc/hour to ensure adequate kidney function. The nurse began IV fluids of 0.9% normal saline at 90 cc/hour because his sodium level was slightly abnormal (131 mmol/L), and monitored oral and IV fluid intake. His urine specific gravity of 1.026 was another indication of dehydration. Although creatinine clearance was normal, protein in his urine indicated kidney function was abnormal.
The presence of large amounts of blood in the urine may have indicated ensuing rhabdomyolysis, a condition with extreme enzyme elevations caused by skeletal muscle destruction. These high enzymes could mean many things, but primarily indicates muscle catabolism and injury possibly caused by hyperthermia and muscle rigidity. The patient’s troponins were normal, which ruled out cardiac muscle involvement. Empiric antibiotic therapy was started to cover the elevated white blood cell (WBC) count and sputum pseudomonas. Dopaminergic medications were administered at the preoperative level to restore dopamine levels.
Discussion
NMS is an uncommon, life-threatening, idiosyncratic reaction to the acute withdrawal of anti-Parkinsonian agents (Sanga & Nomura, 2003). The observed clinical signs demonstrating autonomie dysfunction are hyperthermia, tachycardia, tachypnea, diaphoresis, altered consciousness, and hyper- or hypotension. Other signs of NMS include rigidity, leukocytosis, tremors, and marked elevation of serum CK. A serious complication of NMS is rhabdomyolysis, which is an acute, fulminating, and potentially fatal disease of the skeletal muscles that destroys muscle tissue. It is evidenced by extreme CK levels (12,542 U/L in this patient) , hyperkalemia, myoglobinuria, and acute renal insufficiency. The patient maintained normal serum potassium levels and urinary output and did not develop rhabdomyolysis. With conditions that may involve damage to skeletal muscle, hydration should be adequate to dilute the urine and flush the myoglobin out of the kidney to prevent rhabdomyolysis from occurring (Craig, 2004). Other complications of NMS include respiratory failure, myocardial infarction, hepatic failure, and DIC. The mortality rate is 15%-20% (Davis, Caroff, & Mann, 2000). There have been more than 200 cases of NMS in older adults reported in the medical literature (Nicholson & Chiu, 2004). It appears that even a moderate withdrawal of dopaminergic agents in the older Parkinson’s patient may trigger NMS. Older patients may be more susceptible to NMS because dopamine activity decreases with age (Nicholson & Chiu).
Outcomes
Data indicate the average duration of NMS is approximately 7-10 days (Davis et al., 2000). By the 4th hospital day, his mentation cleared and the elevated enzymes were decreasing. The WBC was normal and hemaruria and proteinuria were absent. Serum sodium level had normalized as well as the BUN. Table 2 demonstrates that the patient’s laboratory results returned to normal on day 7 of his hospital admission and resolution of \NMS, and coincides with this patient’s recovery time. The DBS was turned off on day 7 to prepare for a brain MRI with contrast and because the neurologist wanted to monitor the patient off stimulation for 5 days before it was restarted on day 13 at its preadmission settings. Tremor was visible off stimulation during those 5 days.
This patient survived NMS through the prompt treatment and supportive care given to him upon his hospital admission. However, he required intensive inpatient physical and occupational therapy because of his prolonged bedrest. The length of stay for this hospital admission was 23 days.
Summary
To prevent NMS in Parkinson’s patients, nurses must be cognizant of the narrow safety margin for withdrawing dopaminergic agents. The presence of NMS poses a significant mortality risk for the fragile geriatric population. Nurses who understand this critical condition and who are knowledgeable about the risks, warning signs, and treatment for NMS are able to explain to worried family members the course of treatment and offer realistic hope for a complete recovery.
Acknowledgment
Special thanks to Naomi Nelson, PhD RN, for editing expertise.
References
American Psychiatric Association. (2000). Diagnostic and statistical manual of mental disorders: DSM-IV-TR (pp. 795-798). Washington, DC: Author.
Craig, S. (2004, December 29). Rhabdomyolysis. Retrieved February 8, 2005, from http://www.emedicine.com/emerg/topic508.htm
Davis, J. M., Caroff, S. N., & Mann, S. C. (2000).Treatment of neuroleptic malignant syndrome. Psychiatric Annals, 30,325-334.
Maloni, H., & Ross, A. R (2004). Degenerative disorders. In M.K. Bader & L.R. Littlejohns, (Eds.), AANN core curriculum for neuroscience nursing, (4th ed.), St. Louis, MO: Saunders.
Nicholson, D., & Chiu.W (2004). Neuroleptic malignant syndrome. Geriatrics Advisor, 59(8), 36-40.
Sanga, M., & Nomura, S. (2003).A case of malignant syndrome associated with a Parkinsonism patient. Japanese Journal of Psychopharmacology, 23,91-95.
Questions or comments about this article may be directed to Constance Ward, MSN RN BC, Neurology Care Line-127PD 2002 Holcombe Blvd., Houston, TX 77030, or by e-mail to constance. [email protected]. She is a clinical coordinator, Parkinson’s Research, Education & Clinical Center, Michael E. DeBakey VA Medical Center, Houston, TX.
Copyright 2005 American Association of Neuroscience Nurses 0047- 2606/05/3703/0000160$5.00
Copyright American Association of Neurosurgical Nurses Jun 2005
Comments