Practical aspects in the management of hypokalemic periodic paralysis

Journal of Translational Medicine BioMed Central Open Access Commentary Practical aspects in the management of hypokalemic periodic paralysis Jacob O Levitt1,2 Address: 1President and Medical Director, Periodic Paralysis Association, 155 West 68th Street, #1732, New York, NY 10023, USA and 2Assistant Clinical Professor, Department of Dermatology, The Mount Sinai Medical Center, New York, NY, USA Email: Jacob O Levitt - Published: 21 April 2008 Journal of Translational Medicine 2008, 6:18 doi:10.1186/1479-5876-6-18 Received: 27 November 2007 Accepted: 21 April 2008 This article is available from: http://www.translational-medicine.com/content/6/1/18 © 2008 Levitt; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Abstract Management considerations in hypokalemic periodic paralysis include accurate diagnosis, potassium dosage for acute attacks, choice of diuretic for prophylaxis, identification of triggers, creating a safe physical environment, peri-operative measures, and issues in pregnancy. A positive genetic test in the context of symptoms is the gold standard for diagnosis. Potassium chloride is the favored potassium salt given at 0.5–1.0 mEq/kg for acute attacks. The oral route is favored, but if necessary, a mannitol solvent can be used for intravenous administration. Avoidance of or potassium prophylaxis for common triggers, such as rest after exercise, high carbohydrate meals, and sodium, can prevent attacks. Chronically, acetazolamide, dichlorphenamide, or potassium-sparing diuretics decrease attack frequency and severity but are of little value acutely. Potassium, water, and a telephone should always be at a patient's bedside, regardless of the presence of weakness. Perioperatively, the patient's clinical status should be checked frequently. Firm data on the management of periodic paralysis during pregnancy is lacking. Patient support can be found at http:/ /www.periodicparalysis.org. Introduction Hypokalemic periodic paralysis is a disorder of muscle whereby voltage-gated ion channels (typically calcium or sodium, and less frequently potassium) are mutated, resulting in abnormalities of sarcolemmal excitation. The disease typically first manifests in adolescence as bouts of mild to severe muscle weakness lasting hours and sometimes days associated with hypokalemia triggered most commonly by rest after exercise or high carbohydrate meals. Weakness typically recovers when serum potassium normalizes. In some cases, a fixed weakness can develop, especially in the larger, proximal muscle groups later in life. Lehmann-Horn et al provide a detailed overview of periodic paralysis pathophysiology elsewhere [1]. Being Medical Director of the Periodic Paralysis Association and myself a carrier of the R672S mutation in Nav1.4, encoded by SCN4A (my case was reported by Venance et al [2]), has allowed me to compare the experiences of scores of patients who suffer from muscle ion channelopathies. Through my own experience with primary hypokalemic periodic paralysis, as well as through numerous anecdotes of other sufferers, I have collected some useful insights in dealing with the disorder on a day to day basis. To verify each of these management strategies in a scientifically rigorous way is important but impractical due to the rarity of the periodic paralyses. As such, a good portion of this manuscript represents my personal observations in the management of hypokalemic periodic paralysis. Page 1 of 8 (page number not for citation purposes) Journal of Translational Medicine 2008, 6:18 Discussion Potassium dosing and indications While one could make a physiologic argument for one or another type of potassium salt, in all likelihood, the counter ion is unimportant. It is felt that potassium chloride is best absorbed [3], making this the favored salt in an acute attack. Also, metabolic alkalosis frequently accompanies hypokalemia and Cl- best corrects the alkalosis [4]. That being said, each vehicle – be it oral solution, powder dissolved in water, or sustained release tablet – has its place in management. Oral solution, as measured in mg/mL, can be as effective as powder in water; however, it is cumbersome to convert milligram (mg) dose to mEq dose, and confusion can arise because of this. Indeed, depending on the counter ion, one mg of potassium salt can translate into different mEq amounts. To be safe and consistent, always dose in milliequivalents (mEq). Table 1 is useful for conversion to mEq. Various brands contain combinations of salts, and in these cases, it is critical to read the package insert if dosing on a mg basis rather than a mEq basis. With respect to liquid/aqueous versus sustained release tablet, liquid and aqueous forms of potassium are useful prior to performing known triggers, such as eating a high carbohydrate load and vigorous activity or at the start of an episode of weakness. (Once the vigorous activity is over and rest begins, an attack will often occur without appropriate prophylaxis). In cases where the patient has frequent early morning attacks, a trial of sustained release potassium tablets taken at time of sleep may be warranted. Some may also find it necessary to take sustained release tablets once or twice daily as a standing regimen in combination with immediate release potassium as needed. The downside to chronic potassium administration, especially with the use of sustained release tablets, is gastric irritation from locally high potassium salt concentrations. This problem is often well-controlled with a proton pump inhibitor. The vehicle in which to mix the potassium salt warrants consideration. Water is the favored option. Sports drinks, such as Gatorade®, may at first blush seem intuitively ben- http://www.translational-medicine.com/content/6/1/18 eficial as they contain "electrolytes" and "potassium"; however, they contain high sugar loads and often high sodium content, both of which can trigger attacks in hypokalemic periodic paralysis patients. Potassium should be taken with ample volumes of water, for example, at least 120 mL (about 4 oz) of water per 20 mEq [3]. I have found that dissolving the potassium in the least amount of liquid possible, ingesting in one shot, and following with an 8–12 oz water chaser is more tolerable than drinking a full 8–12 oz of aqueous solution. Potassium can be given orally for attack prophylaxis. Assuming normal renal function, most patients are grossly under-dosed. One can find the appropriate dose by trial and error, or approach it more scientifically. Either way is acceptable. The scientific approach involves measuring serum potassium 20 to 40 minutes after fixed oral potassium loads on separate days. This should provide some confi (...truncated)