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hyperkalemia

Etiology: 1) pseudohyperkalemia a) excessively long tourniquet application before phlebotomy cause K+ to leak from muscle distal to the tourniquet b) hemolysis of specimen during or after phlebotomy c) thrombocytosis > 1E06/mm3 or leukocytosis > 100,000/mm3 - lysis of platelets or leukocytes during clot formation & retraction - determine K+ from plasma rather than serum 2) massive influx of K+ into plasma a) intravenous K+ salts b) oral potassium - dietary excess - salt substitutes - prescribed K+ replacements 3) hemolysis 4) rhabdomyolysis 3) redistribution of K+ from within cells to plasma a) pharmacologic agents - succinylcholine - digitalis overdose - beta-adrenergic receptor antagonists - alpha-adrenergic receptor agonists - arginine & lysine from hyperalimentation b) hyperosmolar states especially hyperglycemia - insulin-deficiency c) metabolic acidosis with normal anion gap - a decrease in pH of 0.1 increases K+ 0.6 meq/L d) hyperkalemic periodic paralysis - may result in hyperkalemia or hypokalemia 4) inadequate renal excretion a) adrenal disorders - hyporeninemic hypoaldosteronism - renal tubular acidosis (RTA) IV - Addison's disease b) defects in tubular secretion - systemic lupus erythematosus (SLE) - obstructive uropathy - sickle cell disease - renal transplant c) renal failure (acute renal failure & chronic renal failure) - special considerations in dialysis patients - extrarenal mechanism of K+ elimination dominate - constipation diminishes GI K+ elimination - fasting diminishes basal insulin levels d) pharmacologic agents: - potassium-sparing diuretics - amiloride - triamterene - spironolactone - agents that inhibit secretion of aldosterone - ACE inhibitors, ARBs - non-steroidal anti-inflammatory drugs (NSAIDs) - heparin - beta-blockers - cytotoxic drugs - cyclosporine A - lithium - trimethoprim (Bactrim, Septra) - pentamidine [3] e) diminished effective plasma volume (low urine flow state) - CHF - cirrhosis - potassium intake from salt substitute in connection with dehydration 5) risk factors a) advanced age b) diabetes mellitus - insulin secretion which results in translocation of K+ intracellularly is the body's major safegaurd against acute hyperkalemia 6) pseudohyperkalemia - mechanical release of K+ from cells during phlebotomy or during specimen processing [3] - marked leukocytosis & thrombocytosis [3] - electrocardiogram is normal Pathology: - defect in renal tubular potassium secretion - defect in the renin-angiotensin-aldosterone axis - GFR < 20 mL/min/1.73 m2 Clinical manifestations: 1) ascending muscle weakness 2) perioral paresthesias 3) symptoms inconsistently present Laboratory: - serum chemistries a) serum potassium: hyperkalemia b) serum creatinine: assess renal function c) serum urea nitrogen: obtain BUN/creatinine ratio d) serum glucose: - hyperglycemia with insulin deficiency e) serum creatine kinase to assess rhabdomyolysis - plasma potassium if leukocytosis (> 100,000/uL) or thrombocythemia* - see ARUP consult [4] * lysis of platelets or leukocytes during clot formation & retraction Special laboratory: - electrocardiogram a) peaked T waves especially in precordial leads* b) shortening of QT interval* c) prolongation of PR interval d) loss of P wave e) widening of QRS complex 1] late change 2] degeneration into sine wave before patient arrest a] ventricular fibrillation b] asystole * earliest changes [3] * only the EKG, not serum potassium can assess effect of hyperkalemia on the cardiac membrane [3] Complications: 1) ventricular arrhythmias 2) cardiac conduction defects 3) cardiac arrest Management: 1) serum K+ < 6.5 meq/L & no EKG changes or peaked T waves only a) identify & correct underlying etiology - 10-30 mL of 10% calcium gluconate* IV push if peaked T waves (NEJM) [18,19] b) loop diuretics - for patients with hypervolemia without advanced renal failure [18] - tubular defects c) thiazide diuretic for chronic hyperkalemia in patients with RTA-4, type 2 diabetes, hypertension & peripheral edema [18] - do not change loop diuretic to thiazide diuretic for hyperkalemia in patients with hyperkalemia & systolic heart failure [18,19] d) hyporeninemic hypoaldosteronism - fludrocortisone (Florinef) e) oral NaHCO3 - useful if metabolic acidosis - enhances Na+ delivery to the distal tubules & K+ excretion f) patiromer or sodium zirconium cyclosilicate (Lokelma) g) dietary potassium restriction 2) serum K+ > 8 meq/L or EKG changes beyond peaked T waves a) continuous EKG monitoring b) IV access c) 10-30 mL of 10% calcium gluconate* IV push - transiently stabilizes myocardial cells - does not lower serum K+ - onset: minutes; duration: 1/2 hour d) IV glucose + insulin - 200 to 500 mL of 10% dextrose - 10 units of insulin IV or SC - over 30 minutes - may repeat several times e) dialysis - hemodialysis, peritoneal dialysis - never the 1st step because of delay in initiation [2] f) NaHCO3 drip (may not be effective in dialysis patients) g) beta 2 adrenergic receptor agonists - albuterol h) continuing influx of K+ into plasma from rhabdomyolysis or tissue necrosis mandates aggressive treatment of hyperkalemia 3) removal of potassium from body [3] - patiromer & sodium zirconium cyclosilicate can increase GI excretion [3] - loop diurectics can increase urinary excretion of potassium [3] - hemodialysis treatment of choice with oliguria 4) drugs probably not useful, may be harmful - avoid, discontinue or decrease dosage of drugs that inhibit K+ excretion; threshold for action 5.5 meq/L [3] - discontinue potassium supplementation if potassium at or above upper end of reference interval - spironolactone increases serum potassium ~0.3 mEq/L (average) [16] - ACE inhibitors & ARBs increase serum K+ by inhibiting production of aldosterone, thus switching from ACE inhibitor to ARB is not useful - discontinuation of ACE inhibitor or ARB may be associated with higher mortality [17] - continuation of ACE inhibitor or ARB may be facilitated by - frequent monitoring of serum potassium, patiromer, discontinuation of beta-blockers [17] - increasing dose of loop diuretic (NEJM) [19] - use hydralazine/isosorbide dinitrate (Bidil) if vasodilator is indicated [3] - patiromer or sodium zirconium cyclosilicate recommended if serum potassium excess threshold for action [3] - 25-50 g of Kayexalate with 1 mL of 70% sorbitol/g Kayexalate - peak effect seen in 4 hours - use is controversial; benefit/risk ratio unfavorable [3] 5) low potassium diet (if other measures fail) [17] 6) GLP-1 agonists & SGLT-2 inhibitors diminish risk of hyperkalemia in patients with diabetes mellitus type-2 taking ACE-inhibitors or ARBs [22] * calcium chloride cannot be given through a peripheral IV because extravasation may cause local tissue necrosis 10]

Interactions

disease interactions

Related

potassium (K+) in serum/plasma renal tubular acidosis (RTA) type IV (distal RTA)

General

electrolyte disorder sign/symptom

Figures/Diagrams

EKG: hyperkalemia

References

  1. Harrison's Principles of Internal Medicine, 13th ed. Companion Handbook, Isselbacher et al (eds), McGraw-Hill Inc. NY, 1995, pg 831
  2. Saunders Manual of Medical Practice, Rakel (ed), WB Saunders, Philadelphia, 1996, pg 671-673
  3. Medical Knowledge Self Assessment Program (MKSAP) 11, 14, 15, 16, 17, 18, 19. American College of Physicians, Philadelphia 1998, 2006, 2009, 2012, 2015, 2018, 2021. - Medical Knowledge Self Assessment Program (MKSAP) 19 Board Basics. An Enhancement to MKSAP19. American College of Physicians, Philadelphia 2022
  4. ARUP Consult: Electrolyte Abnormalities, Life Threatening The Physician's Guide to Laboratory Test Selection & Interpretation https://www.arupconsult.com/content/electrolyte-abnormalities-life-threatening
  5. Nyirenda MJ, Tang JI, Padfield PL, Seckl JR. Hyperkalaemia. BMJ. 2009 Oct 23;339:b4114 PMID: 19854840
  6. Elliott MJ, Ronksley PE, Clase CM, Ahmed SB, Hemmelgarn BR. Management of patients with acute hyperkalemia. CMAJ. 2010 Oct 19;182(15):1631-5. PMID: 20855477 Free PMC Article
  7. Roscioni SS, de Zeeuw D, Bakker SJ, Lambers Heerspink HJ. Management of hyperkalaemia consequent to mineralocorticoid- receptor antagonist therapy. Nat Rev Nephrol. 2012 Dec;8(12):691-9. Review. PMID: 23070570
  8. Medford-Davis L, Rafique Z. Derangements of potassium. Emerg Med Clin North Am. 2014 May;32(2):329-47. Review. PMID: 24766936
  9. Putcha N, Allon M. Management of hyperkalemia in dialysis patients. Semin Dial. 2007 Sep-Oct;20(5):431-9. Review. PMID: 17897250
  10. NEJM Knowledge+. Question of the Week. August 16, 2016 http://knowledgeplus.nejm.org/question-of-week/1137
  11. Gumz ML, Rabinowitz L, Wingo CS. An Integrated View of Potassium Homeostasis. N Engl J Med. 2015 Oct 29;373(18):1787-8. PMID: 26510039 Free Article
  12. Mahoney BA, Smith WA, Lo DS et al. Emergency interventions for hyperkalaemia. Cochrane Database Syst Rev 2005. PMID: 15846652
  13. Kovesdy CP. Updates in hyperkalemia: Outcomes and therapeutic strategies. Rev Endocr Metab Disord. 2017 Mar;18(1):41-47. Review. PMID: 27600582 Free PMC Article
  14. Rossignol P, Legrand M, Kosiborod M et al Emergency management of severe hyperkalemia: Guideline for best practice and opportunities for the future. Pharmacol Res. 2016 Nov;113(Pt A):585-591. Review. PMID: 27693804
  15. Meng QH, Wagar EA. Pseudohyperkalemia: A new twist on an old phenomenon. Crit Rev Clin Lab Sci. 2015;52(2):45-55. Review. PMID: 25319088
  16. Geriatric Review Syllabus, 11th edition (GRS11) Harper GM, Lyons WL, Potter JF (eds) American Geriatrics Society, 2022
  17. Leon SJ et al. Hyperkalemia-related discontinuation of renin-angiotensin-aldosterone system inhibitors and clinical outcomes in CKD: A population-based cohort study. Am J Kidney Dis 2022 Aug; 80:164. PMID: 35085685 https://www.ajkd.org/article/S0272-6386(22)00034-8/fulltext - Palmer BF, Clegg DJ. Managing hyperkalemia to enable guideline-recommended dosing of renin-angiotensin-aldosterone system inhibitors. Am J Kidney Dis 2022 Aug; 80:158 PMID: 35461743 https://www.ajkd.org/article/S0272-6386(22)00522-4/fulltext
  18. NEJM Knowledge+ Nephrology/Urology
  19. NEJM Knowledge+ Complex Medical Care
  20. Liu M, Rafique Z. Acute management of hyperkalemia. Curr Heart Fail Rep. 2019;16:67-74. PMID: 30972536
  21. Palmer BF, Clegg DJ. Physiology and pathophysiology of potassium homeostasis: core curriculum 2019. Am J Kidney Dis. 2019;74:682-695. PMID: 31227226 - Palmer BF, Carrero JJ, Clegg DJ et al Clinical Management of Hyperkalemia. Mayo Clin Proc. 2021 Mar;96(3):744-762 PMID: 33160639 Free article
  22. Fu EL et al. SGLT-2 inhibitors, GLP-1 receptor agonists, and DPP-4 inhibitors and risk of hyperkalemia among people with type 2 diabetes in clinical practice: Population based cohort study. BMJ 2024 Jun 26; 385:e078483. PMID: 38925801 PMCID: PMC11200155 Free PMC article https://www.bmj.com/content/385/bmj-2023-078483