Hyperkalemia-Induced Paralysis Nikita S. Wilson, Pharm.D., Joanna Q. Hudson, Pharm.D., FASN, Zachary Cox, Pharm.D., Tabitha King, Pharm.D., and Christopher K. Finch, Pharm.D. Hyperkalemia is an electrolyte abnormality that can lead to severe consequences. Paralysis induced by hyperkalemia has been described in only a few reports. We describe a 60-year-old man who experienced paralysis presumably due to hyperkalemia. He presented to the emergency department with severe weakness in all extremities. The patient’s serum potassium concentration was greater than 8 mEq/L and his serum creatinine concentration was 7 mg/dl. Findings on electrocardiography were abnormal. Of note, his drug therapy included lisinopril and naproxen. After treatment for hyperkalemia, the patient’s symptoms resolved; however, he was admitted for further workup for renal failure. The patient was discharged after approximately 1 week with a diagnosis of end-stage renal disease. Use of the Naranjo adverse drug reaction probability scale indicated a probable relationship (score of 5) between the patient’s paralysis and hyperkalemia. Although hyperkalemia as a cause of paralysis is extremely rare, clinicians should be aware of this potentially life-threatening, noncardiac toxicity. Key Words: hyperkalemia, paralysis, renal failure. (Pharmacotherapy 2009;29(10):1270–1272) Hyperkalemia is a serious electrolyte abnormality that is potentially life-threatening if it is not quickly identified and appropriately treated. Cardiovascular complications, such as peaked T waves, prolonged PR intervals, or widened QRS complexes, are the most common and serious effects. However, weakness and respiratory compromise can also occur. 1 Causes of hyperkalemia include renal failure, diabetic ketoacidosis, and numerous drugs, such as angiotensin-converting enzyme inhibitors, angiotensin II receptor blockers, nonsteroidal antiinflammatory drugs, -blockers, potassiumsparing diuretics, and trimethoprim.1, 2 From the Department of Pharmacy, Methodist University Hospital (Drs. Wilson and Finch), and the University of Tennessee College of Pharmacy (Drs. Wilson, Hudson, and Finch), Memphis, Tennessee; the Department of Pharmacy, Vanderbilt University Hospital, Nashville, Tennessee (Dr. Cox); and the Department of Pharmacy, Central Arkansas Veterans Healthcare System, Little Rock, Arkansas (Dr. King). Address reprint requests to Christopher K. Finch, Pharm.D., Department of Pharmacy, Methodist University Hospital, 1265 Union Avenue, Memphis, TN 38104; e-mail:
[email protected].
We describe a patient who experienced paralysis presumably due to hyperkalemia. Case Report A 60-year-old African-American man presented to the emergency department with progressive weakness occurring over approximately 3 days. On the day of presentation, severe weakness advanced suddenly in his lower extremities and progressed to the upper extremities over a few hours. In addition, he reported having a concomitant 3-day history of diarrhea (two or three loose stools/day) and nausea and vomiting (two or three episodes/day). He also experienced mild shortness of breath. The patient’s medical history was remarkable for hypertension and cerebrovascular accident, which resulted in only mild dysarthria. His home drug therapy included lisinopril 20 mg twice/day, naproxen 500 mg twice/day, amlodipine 10 mg twice/day, clopidogrel 75 mg/day, and ranitidine 150 mg twice/day. The duration of use for each drug was not determined. The patient stated that he had experienced the adverse drug reaction of an
HYPERKALEMIA-INDUCED PARALYSIS Wilson et al “upset stomach” after taking aspirin. On presentation to the emergency department, the patient had near-paralysis in all extremities and was completely areflexic. Differential diagnoses included stroke, spinal cord decompression, and Guillain-Barré syndrome. Initial findings included a noninvasively measured blood pressure of 156/90 mm Hg, pulse rate 74 beats/minute, temperature 37°C, and a respiratory rate 20 breaths/minute. The patient’s pertinent laboratory findings were sodium 135 mEq/L (normal range 136–144 mEq/L), potassium greater than 8 mEq/L (3.6–5.1 mEq/L), chloride 111 mEq/L (101–111 mEq/L), carbon dioxide 14 mEq/L (22–32 mEq/L), blood urea nitrogen 100 mg/dl (8–20 mg/dl), serum creatinine 7 mg/dl (0.5–1.3 mg/dl), calcium 10.4 mg/dl (8.4–10.2 mg/dl), amylase 281 U/L (36–128 U/L), lipase 202 U/L (22–51 U/L), white blood cell count 13.1 x 10 3 /mm 3 (5–10 x 10 3/mm 3), and platelet count 257 x 10 3/mm 3 (150–400 x 103/mm3). A repeat measurement of the potassium level confirmed greater than 8 mEq/L. No other laboratory samples were taken while the patient was in the emergency department. Electrocardiography showed normal sinus rhythm with QRS widening and T-wave abnormality. The patient’s hyperkalemia was treated with sodium polystyrene sulfonate 45 g given rectally, followed by intravenous regular human insulin 10 U, dextrose 25 g, calcium gluconate 1 g, and sodium bicarbonate 50 mEq. After treatment, the patient’s motor strength returned to near-baseline in all extremities before he left the emergency department. Reflexes in his right and left upper extremities returned to 2+ and 3+, respectively. Bilateral reflexes in his lower extremities were 2+. The patient’s strength returned to near-normal. Magnetic resonance imaging of the cervical spine and brain showed no acute findings. The patient was subsequently admitted to the hospital. The remainder of his hospitalization was focused on his newly identified renal disease. Lisinopril and naproxen were discontinued. He received hemodialysis and was evaluated for acute versus chronic renal insufficiency. He was previously hemodialysis naïve. The patient’s renal function continued to worsen, and endstage renal disease was diagnosed. During the patient’s hospital stay, an arteriovenous fistula was placed for continued dialysis. His condition continued to improve, and he was discharged after a 7-day hospital course. His potassium level was 4.7 mEq/L, and his final diagnosis was end-stage renal disease
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requiring intermittent hemodialysis. Lisinopril and naproxen were not restarted at discharge. Discussion Hyperkalemia-induced paralysis can be divided into two types: hyperkalemic periodic paralysis and hyperkalemic paralysis. In the first type, hyperkalemia or strenuous exercise leads to a sustained depolarization of skeletal muscle cells due to a constant influx of sodium through mutated sodium channels.3 Our patient did not report engaging in strenuous exercise before admission. Depolarization causes action potential inexcitability and paralysis of skeletal muscle. The frequency and severity of attacks are variable. Although serum potassium levels may range from normal to elevated during an attack, hypokalemic periodic paralysis is the most common form.4 In hyperkalemic paralysis, the patient presents with symptoms of hyperkalemia mimicking those of Guillain-Barré syndrome.1, 5 Guillain-Barré syndrome was part of the initial differential diagnosis for our patient as well. The most frequently reported causes of hyperkalemiainduced paralysis are renal insufficiency, use of potassium-elevating drugs, or a combination of the two.5 One case report described hyperkalemiainduced paralysis in a 78-year-old man that was presumably due to enalapril.6 Consistent with these reports, our patient was experiencing renal insufficiency and receiving an angiotensinconverting enzyme inhibitor (lisinopril) and a nonsteroidal antiinflammatory drug (naproxen). In the case reports, potassium levels ranged from 8.1–9.2 mEq/L. 1, 2, 7–9 A review of 17 other patient cases indicated potassium levels ranging from 7–11.2 mEq/L.5 The paralysis is usually ascending, with areflexia and normal sensory function and normal cranial nerves.2 In all case reports we found, paralysis reversed regardless of how the hyperkalemia was treated. As in our patient, reversal occurred almost immediately after treatment, with full strength returning over the next few hours. Although the mechanism of hyperkalemic paralysis remains unknown, it should remain on the list of differential diagnoses of new-onset paralysis or weakness regardless of the cause or magnitude of the hyperkalemia. The Naranjo adverse reaction probability scale is a widely accepted method for systematically assessing the probability of an adverse reaction in a clinical setting.10 Probability is assigned by means
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of a score indicating a doubtful, possible, probable, or definite relationship. According to this scale, the hyperkalemia-induced paralysis in our patient was a probable adverse event (score of 5). Conclusion Hyperkalemia is a serious and potentially lifethreatening electrolyte abnormality. Although rare, hyperkalemic paralysis should be a part of the differential diagnosis of new-onset paralysis or weakness in a patient with elevated serum potassium concentrations. The paralysis reverses quickly after treatment of the hyperkalemia. Offending agents should be identified and eliminated to prevent recurrence, especially in patients with impaired renal function. This case demonstrates the importance of proper monitoring of patients, especially the elderly, who are prescribed drugs (e.g. angiotensinconverting enzyme inhibitors and nonsteroidal antiinflammatory drugs) that may alter renal function and potassium concentrations.
References 1. McCarty M, Jagoda A, Fairweather P. Hyperkalemic ascending paralysis. Ann Emerg Med 1998;32:104–7. 2. Muensterer OJ. Hyperkalemic paralysis. Age Ageing 2003;32:114–15. 3. Weber MA, Nielles-Vallespin S, Essig M, Jurkat-Rott K, Kauczor HU, Lehmann F. Muscle Na+ channelopathies: MRI detects intracellular 23 Na accumulation during episodic weakness. Neurology 2006;67:1151–8. 4. Ryan AM, Matthews E, Hanna MG. Skeletal-muscle channelopathies: periodic paralysis and nondystrophic myotonias. Curr Opin Neurol 2007;20:558–63. 5. Evers S, Engelien A, Karsch V, Hund M. Secondary hyperkalemic paralysis. J Neurol Neurosurg Psychiatry 1998;64:249–52. 6. Dutta D, Fischler M, McClung A. Angiotensin converting enzyme inhibitor induced hyperkalaemic paralysis. Postgrad Med J 2001;7:114–15. 7. Walter E, Gibbins N, Vandersteen A, Kinton BM, Wark P, Jonas M. Hyperkalemic ascending paralysis. J R Soc Med 2004;97:330–1. 8. Pluijmen M, Hersbach F. Sine-wave pattern arrhythmia and sudden paralysis that resulted from severe hyperkalemia. Circulation 2007;116:e2–4. 9. Cheng CJ, Chiu JS, Huang WH, Lin SH. Acute hyperkalemic paralysis in a uremic patient. J Nephrol 2005;18:630–3. 10. Naranjo CA, Busto U, Sellers EM, et al. A method for estimating the probability of adverse drug reactions. Clin Pharmacol Ther 1981;30:239–45.
