<< Evidence-Based Management of Potassium Disorders in the Emergency Department (Pharmacology CME)


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Evidence-based medicine requires a critical appraisal of the literature based upon study methodology and number of subjects. Not all references are equally robust. The findings of a large, prospective, randomized, and blinded trial should carry more weight than a case report.

To help the reader judge the strength of each reference, pertinent information about the study is included in bold type following the reference, where available.

  1. Huang CL and Kuo E. Mechanism of hypokalemia in magnesium deficiency. J Am Soc Nephrol. 2007;2649-2652.
  2. Brophy DF. Disorders of potassium and magnesium homeostasis. In: DiPiro JT, Talbert RL, Yee GC, et al, editors. Pharmacotherapy: A Pathophysiologic Approach. 9th ed. New York, New York: McGraw-Hill; 2014. (Book chapter)
  3. Eliacik E, Yildrim T, Sahin U, et al. Potassium abnormalities in current clinical practice: frequency, causes, severity and management. Med Princ Pract. 2015;24(3):271-275. (Retrospective study; 9045 patients)
  4. Crop MJ, Hoorn EJ, Lindermnas J, et al. Hypokalemia and subsequent hyperkalaemia in hospitalized patients. Nephrol Dial Transplant. 2007;22(12):3471-3477. (Retrospective study, 1178 patients)
  5. Paice BJ, Paterson KR, Onyanga-Omara F, et al. Record linkage study of hypokalemia in hospitalized patients. Postgrad Med J. 1986; 62(725):187-191. (Retrospective study; 58,167 patients)
  6. Jensen HK, Brabrand M, Vinholt PJ, et al. Hypokalemia in acute medical patients: risk factors and prognosis. Am J Med. 2015;128(1):60-67. (Observational cohort study; 11,988 patients)
  7. Squires RD, Huth EJ. Experimental potassium depletion in normal human subjects: relation of ionic intakes to the renal conservation of potassium. J Clin Invest. 1959;38(7):1134-1148. (Prospective study; 11 patients)
  8. Alderman MH, Piller BL, Ford CE, et al. Clinical significance of incident hypokalemia and hyperkalemia in treated hypertensive patients in the antihypertensive and lipid-lowering treatment to prevent heart attack trial. Hypertension. 2012;59(5):926-933. (Prospective study; 33,357 patients)
  9. Brunner FP, Frick PG. Hypokalemia, metabolic alkalosis and hypernatremia due to “massive” sodium penicillin therapy. Brit Med J. 1968;4(5630):550-552. (Case control study; 6 patients)
  10. Panichpisal K, Pernett FA, Selhia S, et al. Gitelman-like syndrome after cisplatin theraphy: a case report and literature review. BMC Nephrol. 2006;7:10. (Case study/review)
  11. Sato K , Feibleman C, Dobson RL. The electrolyte composition of pharmacologically and thermally stimulated sweat: a comparative study. J Invest Dermatol. 1970;55(6):433-438. (Prospective study; 15 patients)
  12. Einhorn LM, Zhan M, Hsu VD et al. The frequency of hyperkalemia and its significance in chronic kidney disease. Arch Intern Med. 2009;169(12):1156-1162. (Retrospective study; 245,808 patients)
  13. Drawz PE, Babineau DC, Rahman M. Metabolic complications in elderly adults with chronic kidney disease. J Am Geriatr Soc. 2012;7(8):310-315. (Retrospective study; 13,874 patients)
  14. Hayes J, Kalantar-Zadeh K, Lu JL, et al. Association of hypo-and hyperkalemia with disease progression and mortality in males with chronic kidney: the role of race. Nephron Clin Pract. 2012;120(1):c8-c16. (Prospective study; 1227 patients)
  15. Sarafidis PA, Blacklock R, Wood E, et al. Prevalence and factors associated with hyperkalemia in predialysis patients followed in a low clearance clinic. Clin J Am Soc Nephrol. 2012;7(8):1234-1241. (Prospective study; 238 patients)
  16. Einhorn LM, Zhan M, Hsu VD, et al. The frequency of hyperkalemia and its significance in chronic kidney disease. Arch Intern Med. 2009;169(12):1156-1162. (Retrospective study; 245,808 patients)
  17. Forsman RW. Why is laboratory an afterthought for managed care organizations? Clin Chem. 1996;42(5):813-816. (Review)
  18. Seimiay M, Yoshida T, Sawabe Y, et al. Reducing the incidence of pseudohyperkalemia by avoiding making a fist during phlebotomy: a quality improvement report. Am J Kidney Dis. 2010;56(4):686-692. (Quality improvement study; 244,992 patients)
  19. Loh T, Sethi S. A multidisciplinary approach to reducing spurious hyperkalemia in hospital outpatient clinics. J Clin Nurs. 2015;24(19-20):2900-2906. (Quality improvement study)
  20. Kitamura K, Tomita K. Familial psuedohyperkalemia: a rare syndrome, but diverse genetic heterogeneity. Intern Med. 2005;44(8):781-782. (Case series; 6 patients)
  21. Khodorkovsky B, Cambria B, Lesser M, et al. Do hemolyzed potassium specimens need to be repeated? J Emerg Med. 2014;47(3):313-317. (Prospective study; 45 patients)
  22. Gurwitz JH, Field TS, Harrold LR, et al. Incidence and preventability of adverse drug events among older persons in the ambulatory setting. JAMA. 2003;289(9):1107-1116. (Retrospective study; 27,617 patients)
  23. Perazella M. Drug-induced hyperkalemia: old culprits and new offenders. Am J Med. 2000;109(4):307-314. (Review)
  24. Raza S, Baig MA, Chang C, et al. A prospective study on red blood cell transfusion related hyperkalemia in the critically ill. J Clin Med Res. 2015;7(6):417-421. (Prospective study; 125 patients)
  25. Thiele A, Rehman HU. Hyperkalemia caused by penicillin. Am J of Med. 2008;121(8):e1-e2. (Case study; 1 patient)
  26. Mercer CW, Logic JR. Cardiac arrest due to hyperkalemia following intravenous potassium administration. Chest. 1973;64(3):358-359. (Case study; 1 patient)
  27. Raebel MA. Hyperkalemia associated with the use of angiotensin converting enzyme inhibitors and angiotensin receptor blockers. Cardvasc Ther. 2012;30(3):e156-e166. (Review)
  28. Zimran A, Kramer M, Plaskin M, et al. Incidence of hyperkalemia induced by indomethacin in a hospital population. Br Med J (Clin Res Ed). 1985;291(6488):107-108. (Prospective study; 50 patients)
  29. Aljadhey H, Tu W, Hansen RA, et al. Risk of hyperkalemia associated with selective COX-2 inhibitors. Pharmacoepidemiol Drug Saf. 2010;19(11):1194-1198. (Retrospective study; 404 patients)
  30. Lafrance JP, Miller DR. Dispensed selective and nonselective nonsteroidal anti-inflammatory drugs and the risk of moderate to severe hyperkalemia: a nested case control study. Am J Kid Dis. 2012;60(1):82-89. (Case-control study; 18,326 patients)
  31. Nguyen AT, Gentry CA, Furrh RZ. A comparison of adverse drug reactions between high and standard dose trimethoprim-sulfamethoxazole in the ambulatory setting. Curr Drug Saf. 2013;8(2):114-119. (Retrospective study; 982 patients)
  32. Gentry CA, Nguyen AT. An evaluation of hyperkalemia and serum creatinine elevation associated with different dosage levels of outpatient trimethoprim-sulfamethoxazole with or without concomitant medications. Ann Pharmacother. 2013;47(12):1618-1626. (Retrospective study; 6162 patients)
  33. Antoniou T, Hollands S, MacDonald EM, et al. Trimethoprim-sulfamethoxazole and risk of sudden death in patients taking spironolactone. CMAJ. 2015;187(4):E138-E143. (Case-control study; 11,968 patients)
  34. Antoniou T, Gomes T, Mamdani M, et al. Trimethoprim-sulfamethoxazole induced hyperkalemia in elderly patients receiving spironolactone: nested case control study. BMJ. 2011;343:d5228. (Case-control study; 6903 patients)
  35. Marti G, Schwarz C, Leichtle AB, et al. Etiology and symptoms of severe hypokalemia in emergency department patients. Eur J Emerg Med. 2014;21(1):46-51. (Retrospective study; 43,805 patients)
  36. Lin SH, Lin YF, Chen DT, et al. Laboratory tests to determine the cause of hypokalemia and paralysis. JAMA Intern Med. 2004;164(14):1561-1566. (Prospective study; 43 patients)
  37. Tsuji H, Venditti FJ, Evans JC, et al. The association of levels of serum potassium and magnesium with ventricular premature complexes (the Framingham Heart study). Am J Cardiol. 1994;74(3):232-235. (Retrospective study; 3327 patients)
  38. Mattson N, Sadjadieh G, Kumarathurai P, et al. Ambulatory cardiac arrhythmias in relation to mild hypokalaemia and prognosis in community dwelling middle aged and elderly subjects. Europace. 2016;18(4):585-591. (Retrospective study; 671 patients)
  39. Krijthe BP, Herringa J, Kors JA et al. Serum potassium levels and the risk of atrial fibrillation: the Rotterdam Study. Int J Cardiol. 2013;168(6):5411-5415. (Retrospective study; 4059 patients)
  40. Acker CG, Jonson JP, Palevsky PM, et al. Hyperkalemia in hospitalized patients: causes, adequacy of treatment and the results of an attempt to improve physician compliance with published therapy guidelines. Arch Intern Med. 1998;158(8):917-924. (Retrospective study; 127 patients)
  41. Sibbald M, Davies EG, Dorian P, et al. Electrocardiographic interpretation skills of cardiology residents: are they competent? Can J Cardiol. 2014;30(12):1721-1724. (Prospective study; 29 patients)
  42. Wrenn KD, Slovis CM, Slovis BS. The ability of physicians to predict hyperkalemia from the ECG. Ann Emerg Med. 1991;20(11):1229-1232. (Prospective observational study)
  43. Cohn JN, Kowey PR, Whelton PK, et al. New guidelines for potassium replacement in clinical practice. Arch Intern Med. 2000;160(16):2429-2436. (Consensus review)
  44. Macdonald JE, Struthers AD. What is the optimal serum potassium level in cardiovascular patients? J Am Coll Cardiol. 2004;43(2):155-161. (Review)
  45. Whelton PK, He J, Cutler JA, et al. Effects of oral potassium on blood pressure: meta-analysis of randomized controlled trials. JAMA. 1997;277(20):1624-1632. (Meta-analysis)
  46. Viera AJ, Wouk N. Potassium disorders: hypokalemia and hyperkalemia. Am Fam Physician. 2015;92(6):487-495. (Review)
  47. Naljayan M, Kumar S, Steinman T, et al. Hypomagnesemia and hypokalemia: a successful oral therapeutic approach after 16 years of potassium and magnesium intravenous replacement therapy. Clin Kidney J. 2014;7(2):214-216. (Case and review)
  48. Mahoney BA, Smith WA, Lo D, et al. Emergency interventions for hyperkalemia. Cochrane Database Syst Rev. 2005;Apr 18(2):CD003235. (Review)
  49. Hall AB, Salazar M, Larison DJ. The sequencing of medication in the management of hyperkalemia. J Emerg Nurs. 2009;35(4):339-342. (Review)
  50. Allon M, Copkeny C. Albuterol and insulin for treatment of hyperkalemia in hemodialysis patients. Kid Int. 1990;38(5):869-872. (Prospective study, 12 patients)
  51. Apel J, Reutrakul S, Baldwin D. Hypoglycemia in the treatment of hyperkalemia with insulin in patients with end stage renal disease. Clin Kidney J. 2014;7(3):248-250. (Retrospective study; 221 patients)
  52. Schafer S, Naunheim R, Vijayan A, et al. Incidence of hypoglycemia following insulin based acute stabilization of hyperkalemia treatment. J Hosp Med. 2012;7(3):239-242. (Retrospective study; 219 patients)
  53. Chothia MY, Halperin ML, Rensberg MA, et al. Bolus administration of intravenous glucose in the treatment of hyperkalemia: a randomized controlled trial. Nephron Physiol. 2014;126(1):1-8. (Prospective crossover; 10 patients)
  54. Allon M, Shanklin N. Effect of bicarbonate administration on plasma potassium in dialysis patients: interactions with insulin and albuterol. Am J Kid Dis. 1996;28(4):508-514. (Prospective crossover study)
  55. Sowinski KM, Cronin D, Mueller BA, et al. Subcutaneous terbutaline use in CKD to reduce potassium concentrations. Am J Kidney Dis. 2005;45(6):1040-1045. (Prospective study; 14 patients)
  56. Scherr L, Ogden DA, Mead, et al. Management hyperkalemia with a cation exchange resin. N Engl J Med. 1961;264:115- 119. (Prospective study; 32 patients)
  57. Batternick J, Lin J, Au Yeung SH, et al. Effectiveness of SPS for short term treatment of hyperkalemia. Can J Hosp Pharm. 2015;68(4):296-303. (Retrospective study; 138 patients)
  58. Harel Z, Harel S, Shah P, et al. Gastrointestinal adverse events with SPS use: a systematic review. Am J Med. 2013;126(3):264e9-264e24. (Systematic review; 58 cases)
  59. Stavros F, Yang A, Leon A, et al. Characterization of structure and function of ZS-9, a K selective ion trap. PLoS One. 2014;9(12):e114686. (Review article)
  60. Ash SR, Singh B, Lavin PT, et al. A phase 2 study on the treatement of hyperkalemia in patients with chronic kidney disease suggests that the selective potassium trap, ZS-9, is safe and efficient. Kidney Int. 2015;88(2):404-411. (Prospective study; 92 patients)
  61. Packham DK, Rasmussen HS, Lavin PT, et al. Sodium zirconium cyclosilicate in hyperkalemia. NEJM. 2015;372(3):222- 231. (Prospective randomized controlled trial; 754 patients)
  62. Kosiborod M, Rasmussen HS, Lavin P, et al. Effect of sodium zirconium cyclosilicate on potassium lowering for 28 days among outpatients with hyperkalemia. JAMA. 2014;312(12):2233-2233. (Prospective study; 258 patients)
  63. Anker SD, Kosiborod M, Zannad F, et al. Maintenance of serum potassium with sodium zirconium cyclosilicate (ZS-9) in heart failure patients: results from a phase 3 randomized, double blind, placebo controlled trial. Eur J Heart Fail. 2015;17(10):1050-1056 (Prospective study; 94 patients)
  64. Weir MR, Bakris GL, Bushinsky DA, et al. Patiromer in patients with kidney disease and hyperkalemia receiving RAAS inhibitors. NEJM. 2015;372(3):211-221. (Prospective study; 237 patients)
  65. Pitt B, Anker SD, Bushinsky DA, et al. Evaluation of the efficacy and safety of RLY5016, a polymeric potassium binder, in a double blind placebo controlled study in patients with chronic heart failure (the PEARL-HF) trial. Eur Heart J. 2011;32(7):820-828. (Prospective study; 105 patients)
  66. Bakris GL, Pitt B, Weir MR, et al. Effect of patiromer on serum potassium level in patients with hyperkalemia and diabetic kidney disease: the AMETHYST-DN randomized clinical trial. JAMA. 2015;314(2):151-160. (Prospective study; 306 patients)
  67. Gutzeiller JP, Schneditz D, Huber AR, et al. Increasing blood flow increases K+/V (urea) and potassium removal but fails to improve phosphate removal. Clin Neph. 2003;59(2):103- 136. (Prospective crossover study; 13 patients)
  68. Zehnder C, Gutzwiller JP, Huber AR, et al. Low potassium and glucose free dialysis maintains urea but removes potassium. Neph Dial Transplant. 2001;16(1):78-84. (Prospective study; 12 patients)
  69. Blaine A, Ract C, Leblanc P, et al. The limits of succinylcholine for critically ill patients. Anesth Analg. 2012;115(4):873- 879. (Prospective observational study; 153 patients)
  70. Su J, Fu X, Ma Y, et al. Additional predictive value of serum potassium to thrombosis in myocardial infarction risk score for early malignant ventricular arrhythmias in patients with acute myocardial infarction. Am J Emerg Med. 2012;30(7):1089-1094. (Retrospective study; 468 patients)
  71. Grodzinsky A, Goyal A, Gosch K et al. Prevalence and prognosis of hyperkalemia in patients with acute myocardial infarction. Am J Med. 2016;129(8):858-865. (Retrospective study; 38,689 patients)
  72. Bismuth C, Gaultier M, Conso F, et al. Hyperkalemia in acute digitalis poisoning: prognostic significance and therapeutic implications. Clin Toxicol. 1973;6(2):153-162.
  73. Fontaine B. Periodic paralysis. Adv Genet. 2008;63:3-23. (Review)
  74. Venance SL,Cannon SC, Fialho D, et al. The primary periodic paralyses: diagnosis, pathogenesis and treatment. Brain. 2006;129(Pt 1):8-17. (Review)
  75. Lin SH, Lin YF, Chen DT, et al. Laboratory tests to determine the cause of hypokalemia and paralysis. Arch Intern Med. 2004;164(14):1561-1566. (Prospective study; 43 patients)
  76. Flinn RB, Merrill JP, Welzant WR. Treatment of the oliguric patient with a new sodium exchange resin and sorbitol; a preliminary report. NEJM. 1961 Jan 19;264:111-115. (Prospective study; 16 patients)
Publication Information

John Ashurst, DO, MSc; Shane R. Sergent, DO; Benjamin J. Wagner, DO

Publication Date

November 1, 2016

CME Expiration Date

December 1, 2019

CME Credits

4 AMA PRA Category 1 Credits™, 4 ACEP Category I Credits, 4 AAFP Prescribed Credits, 4 AOA Category 2-A or 2-B Credits.
Specialty CME Credits: Included as part of the 4 credits, this CME activity is eligible for 2 Pharmacology CME credits

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CME Information

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Advances In Diagnosis And Management Of Hypokalemic And Hyperkalemic Emergencies (FREE) - Emergency Medicine Practice, February 2012

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