Virtual Potassium for the Intern (and other related electrolytes)

1. Virtual Potassium for the Intern(and other related electrolytes) Summer Intern Lecture Series July 2019 Scott Pawlikowski, M.D.

2. Goals of this Lecture • SESSION OBJECTIVES • Learn to effectively assess and manage hyperkalemia • Learn to address various electrolyte deficiencies (low K+, low Mg2+, low phos, low Ca2+) • Learn what serum electrolyte levels to follow in the hospital, and how often to follow them • Apply your knowledge to real cases! • LEARNING METHODS • Lecture/material review • Interactive case scenarios • Real cases and real intern approaches to electrolyte disorders

3. What this lecture IS: • A practical approach to handling electrolyte disorders in MOST hospitalized patients • A guideline for supplementing electrolytes based on experiential and some evidence-based medical recommendations • Hopefully an informative and useful tool

4. What this lecture IS NOT: • A be-all, end-all list of all the causes of hyperkalemia, hypokalemia, etc. • A thorough review of all the large center, prospective, randomized controlled trials on electrolyte replacement • There really aren’t any!!! • A complete reference that applies to every patient you will treat

5. Some Electrolyte Reference Ranges and Units (Hines VA) • Potassium: 3.5 – 4.7 mmol/L • Magnesium: 1.7 – 2.4 mg/dL • Phosphorus: 2.5 – 4.9 mg/dL • Calcium: 8.5 – 10.1 mg/dL

6. Hyperkalemia Overview • Commonly encountered in hospitalized patients • Most feared consequence: • PEA • Asystole • Urgent vs. Emergent therapy? • Stepwise approach

7. Approach to Hyperkalemia: Step 1 • Is it real? • Assess for/exclude pseudohyperkalemia • Hemolysis—ask RN/phlebotomist/lab tech • If suspected—order STAT repeat K+ level • Potassium infusion—ask RN • If suspected—order STAT repeat K+ level from peripheral vein AWAY from infusion site • Check CBC (WBC > 70K, PLT > 1,000) • K+ moves out of WBC’s, PLT’s after clotting • If suspected—order STAT serum/plasma K+ levels • if serum K+ > plasma K+ by more than 0.3mEq/L, suspect pseudohyperkalemia • In any case, have low threshold to repeat labs

8. Approach to Hyperkalemia: Step 2 • If real, why did it happen? • Acute or chronic renal failure • Medications (K+ sparing diuretics, ACE inhibitors, ARB’s, BB’s, digoxin, etc.) • Endocrinopathies (hypoaldo, Addison’s) • K+ supplements or salt substitutes • K+ in IV infusions/TPN

9. Approach to Hyperkalemia: Step 3 • Is this an emergency? • Did the K+ increase quickly? • If yes, treat as emergency • How high is the potassium level? • If serum K+ ≥7.0 mEq/L, treat as emergency • Any EKG changes of cardiac instability? • If yes, treat as emergency • Remember, the lack of EKG changes is NOT always entirely reassuring

10. Approach to Hyperkalemia: Step 3 • EKG assessment • Four stages of EKG changes • Peaked T waves • PR prolongation/loss of P wave (unstable) • QRS widening (unstable) • Sine waves (very unstable) • The “fifth” and final stage if hyperkalemia not addressed… • PEA or asystole (i.e. cardiac arrest)

11. Approach to Hyperkalemia: Step 4 • Emergency therapy • Part A: oppose toxic effects on cell membrane • IV calcium infusion • Chloride: 3x the elemental calcium of gluconate • Gluconate: less toxic if IV extravasates • Give 10mL ampule of 10% Calcium chloride vs. gluconate over 2-5 minutes • Too fast—pukey pukey!!! • Can repeat in 3-5 minutes if no EKG effect • Keep EKG machine attached to patient!!! • EKG changes will diminish in 1-3 minutes

12. Approach to Hyperkalemia: Step 4 • Emergency therapy • Part B: Shift K+ into cells • Will buy you 1-4 hours time to set up other Rx • Insulin/dextrose therapy • Regular insulin10 units IV push • 50% Dextrose (“D50”) 1 ampule IV push • Can also consider D5W infusion in a fasting patient to stimulate insulin release • Adjuncts (usually not necessary) • Albuterol nebulizer (continuous neb) • Sodium bicarbonate 1 ampule IV push • Only really helpful with coexistant acidosis • Beware rebound hyperkalemia!!!

13. Approach to Hyperkalemia: Step 5 • Direct elimination of K+ from body • Usually takes 4-6 hours to work • Lasix with/without saline infusion? • Works best when volume overloaded (lasix alone) • Hemodialysis (always discuss with renal fellow) • In severe cases • What about ion exchange resins (e.g. Kayexalate)?

14. What About Ion Exchange Resins? • Historical milestones • 1958: Kayexalate as SPS alone FDA approved • 4 years prior to regulations requiring companies to prove efficacy/safety • Initially caused severe constipation and intestinal impactions • 1961: research suggests synergistic effects when Kayexalate SPS co-administered with laxatives like sorbitol • 1982: new Kayexalate premade solution of SPS and sorbitol hits the market • 2005: FDA starts receiving reports of adverse events including death with oral/rectal Kayexalate

15. What About Ion Exchange Resins? • Historical milestones (continued) • 2006: Carolina Medical (maker of Kayexalate) meets with FDA, allowed to continue marketing Kayexalate • Claims that prior harm was from 70% sorbitol solutions • “Carolina Solution”: 33% sorbitol • Not a single report of adverse event since 1982 with Carolina solution, despite extensive use of product (>5 million doses annually) • 2009: Southern Medical Journal article raises concerns of colonic necrosis associated with SPS/sorbitol prep (including some having “Carolina Solution”) • 2009, 2011: FDA issues warnings regarding SPS/sorbitol use and colonic/intestinal necrosis

16. What About Ion Exchange Resins? • Historical milestones (continued) • 2015: FDA requires Kayexalate manufacturer (now Concordia Pharmaceuticals) to conduct studies to investigate potential to bind to other medications administered by mouth, reducing their efficacy • 2015: FDA approves use of patiromer (marketed as Valtessa), a new ion exchange resin, for use in hyperkalemia (following Phase 3 trial published in NEJM 1/15/2015) • Primarily studied in chronic hyperkalemia patients with CKD and concomitant RAAS inhibitor usage

17. What About Ion Exchange Resins? • What to do with Kayexalate? • Uncontrolled studies show benefit, and uncontrolled studies show harm, with and without concomitant sorbitol use • Difficult to weigh the overall trend of evidence • Local nephrology expertise with decades of experience have not found harm with the drug • This is admittedly anecdotal evidence • Recommend cautious SPS use without sorbitol when needed in certain patients when other measures have failed or are not possible (at least in short term)

18. What About Ion Exchange Resins? • Kayexalate contraindications • Postoperative state • Current ileus • Opiate therapy • Large or small bowel obstruction • Underlying bowel disease (IBD, C.diff, e.g.) • Patiromer for emergency use? • May not be readily available at your institution • Has a delayed onset of action, so may not be practical • Costs more compared to Kayexalate

19. Approach to Hyperkalemia: Step 6 • Housekeeping/Follow Up • Try to reverse/prevent/treat the cause • Treatment of acute kidney injury • Medication adjustment • Low Potassium diet • Monitor and reassess closely • Should check serum K+ 4-8 hours after Rx initiated • Beware of rebound hyperkalemia, especially if cellular shift Rx used!! • ALWAYS discuss digitalis-toxicity associated hyperkalemia with your senior resident!!! • Calcium infusion can potentiate the toxicity!!!

20. Hypokalemia Overview • Occurs in over 20% of hospitalized patients • Dangers • Arrhythmia • Rhabdomyolysis • Paralysis • Usually does NOT require emergency supplementation over minutes to hours

21. Approach to Hypokalemia: Step 1 • Redistribution or depletion? • Redistribution causes (cellular shift) • Insulin therapy (usually in DKA) • Beta 2 agonists (e.g. albuterol) • Metabolic alkalosis • Replacing K+ in these settings may cause overshoot and hyperkalemia

22. Approach to Hypokalemia: Step 1 • Redistribution or depletion? • Depletion causes (common) • GI tract losses (diarrhea, vomiting) • Loop/thiazide diuretic therapy • Other medications (e.g. amphotericin B) • Osmotic diuresis (DKA) • Refeeding syndrome (NEVER underestimate!) • Endocrinopathies (Conn’s syndrome, e.g.) • Salt wasting nephropathies/RTA’s • Magnesium deficiency (NEVER overlook!)

23. What is Refeeding Syndrome? • Spectrum of electrolyte/volume disorders • Occurs when previously malnourished patients are fed carbohydrate loads (PO or IV!) • Triggered by intense insulin secretion • Low phos/K+/Mg2+ (sometimes low blood sugar) • Severe cases with unexplained CHF-like picture • First identified/described in liberated POW’s, concentration camp survivors from WWII

24. Approach to Hypokalemia: Step 2 • Estimate the deficit • For every 100 mEq below normal, serum K+ usually drops by 0.3 mEq/L • Highly variable from patient to patient, however!! • Dr. Popli’s estimation scheme • For every 10 mEq below normal, serum K+ usually drops by 0.1 mEq

25. Approach to Hypokalemia: Step 3 • Choose route to replace K+ • In nearly all situations, ORAL replacement PREFERRED over IV • Oral is quicker • Oral has less side effects (IV burns!) • Oral is less dangerous • Choose IV therapy ONLY in patients who are NPO (for whatever reason) or who have severe depletion

26. Approach to Hypokalemia: Step 4 • Choose K+ preparation • Oral therapy • Potassium Chloride is PREFERRED AGENT • Especially useful in Cl-responsive metabolic alkalosis • Potassium Phosphate useful when coexistant phosphorus deficiency • Often useful in DKA patients • Potassium bicarbonate, acetate, gluconate, or citrate useful in metabolic acidosis (“-ate” = bicarb former)

27. Approach to Hypokalemia: Step 4 • Choose K+ preparation • IV therapy • Adjunct to maintenance fluids (10-20 mEq/L) • “The surgical intern’s way” • Try to avoid using it!!! • you often forget it’s there • hyperkalemia can then develop, especially in patients that get ARF in the hospital • IV rider/”piggyback” (+/- lidocaine) • Generally 40-60 mEq • KCl is PREFERRED AGENT again • Can also use KPhos, Kbicarb, etc. • Avoid dextrose solution (trigger insulin, shift K+)

28. Approach to Hypokalemia: Step 5 • Choose dose/timing • Mild/moderate hypokalemia • 3.0 to 3.5 mEq/L • 60-80 mEq PO (or IV) QDay divided doses • Sometimes will require up to 160 mEq per day (refeeders, lots of diarrhea, IV diuretics) • Avoid too much PO at once • GI upset or just poor response • Usually divide as BID or TID dosing

29. Approach to Hypokalemia: Step 5 • Choose dose/timing • Severe hypokalemia (< 3.0 mEq/L) • Can use combination of IV and PO, again with PO preferred if at all possible • Avoid more than 60-80 mEq PO in a single dose • Avoid IV infusion rates >20 mEq/hour • Can cause arrhythmia!!! • Most RN protocols won’t allow >10 mEq/hour rates on the floors (ICU’s too?)

30. Approach to Hypokalemia: Step 6 • Monitor/reassess • Severe hypokalemia, DKA patients • Reassess labs Q4-6 hours • Moderate hypokalemia, IV diuresis patients • Reassess labs BID to TID as needed • Mild hypokalemia • Reassess labs QDay or less as needed

31. Approach to Hypokalemia: Step 7 • Housekeeping/Follow Up • BE AGGRESSIVE in DKA patients and IV diuresis patients • “Moran’s Rule” for cardiac patients: keep K+ > 4.0 or even 4.5 mEQ/L • BE GENTLE in patients with acute or chronic renal failure, and monitor very closely • Cut dose in half • Double dosing interval • Do not replace at all • NEVER forget to check for and treat hypomagnesemia in refractory hypokalemia!!!

32. Hypomagnesemia Overview • Most of total body magnesium is intracellular • Serum levels may NOT reflect intracellular status • Low intracellular Mg2+ can occur in the setting of low, normal, and high serum magnesium levels • Highest risk patients for hypomagnesemia • Alcoholics • Diabetics • Critically ill patients • Refeeding syndrome patients • Rare symptoms (most patients asymptomatic) • Neurologic • Muscular • Cardiac

33. Causes of Hypomagnesemia • Poor PO intake and malabsorptive syndromes • Alcohol ingestion (renal losses) • Thiazide/loop diuretic administration • Amphotericin administration • Acute/chronic diarrhea • DKA • Refeeding syndrome • Inadequate TPN dosing • Diabetes mellitus? (at least an association)

34. Approach to Hypomagnesemia • Unlike potassium replacement, magnesium replacement usually involves IV replacement • All PO magnesium salts are all poorly absorbed • High doses of PO magnesium usually leads to diarrhea • Conversion rule: 8 mEq of magnesium sulfate equals 1 gram of magnesium sulfate (Hines CPRS)

35. Approach to Hypomagnesemia • Rx in hospitalized patients • 1.6-2.0 mg/dL • Give 2-4 gram IVPB (16-32 mEq) • Usually infused at 1 gram/hour • 1.0-1.6 mg/dL • Give 4-8 gram IVPB (32-64 mEq), usually in divided doses BID to TID • <1.0 mg/dL • Can give up to 8-12 gram IVPB (64-96 mEq) in a single day, would divide into three-four doses

36. Approach to Hypomagnesemia • Treating chronic low Mg2+ patients • Give oral magnesium salt daily • Sulfate, oxide, hydroxide, citrate, lactate, chloride, and gluconate available • Gluconate less likely to cause diarrhea • Periodic IM/IV dosing if/when needed • My approach: Magnesium Oxide 420mg PO QDay to TID, based on level and tolerability

37. Approach to Hypomagnesemia • Housekeeping/Follow Up • BE AGGRESSIVE in DKA patients and IV diuresis patients • “Moran’s Rule” for cardiac patients: keep Mg2+ > 2.0 or even 2.5 mEQ/L • BE GENTLE in patients with acute or chronic renal failure, and monitor very closely • Cut dose in half • Double dosing interval • Do not replace at all

38. Hypophosphatemia Overview • Phosphorus is a critically important element in every cell • Remember what the “P” stands for in ATP? • Low phos commonly encountered in hospitalized patients • Feared complication of severe deficiency is rhabdomyolysis

39. Causes of Hypophosphatemia • Refeeding syndrome • DKA • Vitamin D deficiency • Malabsorptive syndromes • Alcoholism • Inadequate TPN dosing

40. Approach to Hypophosphatemia • Rx in hospitalized patients • Mild to moderate hypophosphatemia • 1.5 -2.4 mg/dL • Give phosphorus in the form of K+ or Na+ salts PO BID to TID as needed • Usually given as 1-2 packets of “neutraphos” BID to TID • Severe deficiency • <1.5 mg/dL • Give IVPB in the form of sodium or potassium phosphate • Usually given as 20-40 mEq/mmol rider infused over 2-4 hours • Reasess labs QDay to TID as needed

41. Hypocalcemia Overview • Hypocalcemia in hospitalized patients is usually spurious and/or DOES NOT need to be treated • Aggressive management of hypocalcemia is usually ONLY indicated in “symptomatic” patients • Active or latent tetany • Cardiac dysrhythmia/prolonged QT

42. Hypocalcemia Overview • Spurious hypocalcemia: low albumin • Corrected Ca2+ = measured Ca2+ + [(normal albumin - measured serum albumin) x 0.8] • Works well unless albumin < 2 mg/dL • Hypocalcemia due to hyperphosphatemia from CKD/ESRD • Aggressive calcium replacement is DANGEROUS—serum/tissue precipitation!!! • Treat high phos and calcium level will improve • Renal consults/senior resident can help with phosphate binder dosing/orders

43. Hypocalcemia Overview • IV Calcium infusion can cause skin and muscle necrosis if it extravasates from IV • May threaten limb or necessitate skin grafting!!! • If replacement is needed, can usually give TUMS PO • Severe depletion: discuss IV dosing with senior resident or endo consults • Maintenance calcium replacement in TPN usually handled by nutrition support team

44. Recap of Major Learning Points • Hyperkalemia • Make sure it’s real • Determine emergent or not • Rate of rise, degree of hyperkalemia, EKG • Treat emergent cases with calcium gluconate, insulin, dextrose, and kayexalate +/- dialysis/lasix • Monitor closely for response to treatment—watch for rebound • Fix the cause if possible

45. Recap of Major Learning Points • Hypokalemia • PO almost always preferred over IV • KCl is preferred preparation • Don’t give too much too quickly • Be aggressive in DKA and IV diuresis patients • Be gentle in renal failure patients • Don’t forget to check magnesium levels in refractory patients

46. Recap of Major Learning Points • Hypomagnesemia • IV almost always preferred over PO • Give IVPB in 2 gram increments • Be aggressive in DKA patients, IV diuresis patients, and alcoholics • Be gentle in renal failure patients • PO does not work well and in high doses causes diarrhea

47. Recap of Major Learning Points • Hypophosphatemia • Can be treated with neutraphos packets PO BID/TID in mild cases • Can be treated with sodium or potassium phosphate IVPB’s in severe cases • Hypocalcemia • Usually spurious or does not require Rx • Avoid calcium replacement in CKD/ESRD patients with hyperphosphatemia • Avoid IV calcium whenever possible • Call for help if hypocalcemia really needs IV Rx

48. Getting Labs on Patients • BMP • QDay or Qother day on most hospitalized patients, especially if they have PO intake issues or are on maintenance fluids • BMP with Mg levels • QDay-BID on cardiology patients, alcoholics, and patients on amphotericin B • BMP with Mg/Phos levels • QDay-TID on tube feeding patients, DKA patients, or patients with suspected refeeding syndrome • BMP with Ca/Mg/Phos levels • QDay-4x/Day on TPN patients, AKI/CKD/ESRD patients, oncology patients (chemo/TLS), pancreatitis patients, critically ill patients

49. Ok, You Think You Got It??? • Let’s try it out on some cases • 3 Real cases from real patients at Hines • Figure out what you would do... • …then I’ll show you what the intern actually DID and what actually happened!

50. Case #1 • A 56 y/o male presents due to increased swelling in his face, legs, and abdomen, as well as increasing SOB and DOE. He is volume overloaded on exam. His labs are listed below. His serum albumin is 2.5 g/dL. Would you replace or treat anything?