This document discusses hyperkalemia (high potassium levels), including its causes, effects on the heart, diagnosis, and treatment. It describes a case report of a 69-year-old woman who experienced hyperkalemia after dialysis. Her symptoms included abdominal pain, fatigue, and arrhythmia. Treatment involved calcium, insulin, glucose, and emergent dialysis to lower her potassium level. The document then provides details on potassium regulation in the body, effects of high potassium on heart function, electrocardiogram changes seen with hyperkalemia, common causes, and approaches for treating acute hyperkalemia including membrane stabilization, promoting potassium influx, and potassium removal methods like dialysis or sodium polystyrene sulfonate.

1. Hyperkalemia: Management and Facts
DR HAN NAUNG TUN
MBBS(YGN), MAAFP (USA), MACTM(AUST)
CERTIFICATE IN ADVANCED CARDIAC CARE ( AMERICAN HEART ASSOCIATION)
PROFESSIONAL MEMBERSHIP OF EUROPEAN SOCIETY OF CARDIOLOGY AND WORKING GROUPS

2. Case Report
 69 year old women with ESRD experienced the sudden onset of crampy
abdominal pain and emesis several hours after a routine HD treatment.
 Severe fatigue and dysphoria
 Taken to Emergency department, where she continued having severe
fatigue but denied chest pain , palpitation, dyspnea, pre syncopal
symptoms, fever , or additional GI discomfort .
Physical signs in examination
 Ashen skin
 BP 141/87 mmHg
 Pulse 100 bpm
 RR 32 times/min
 SPO2 97% on 3 L of O2 via nasal cannula

3.  Heart Sounds were normal and both lung fields were clear .
 Abdominal examinations were normal
 Extremities were healthy without cyanosis or edema.
 Neurologically , she was alert and oriented with diminished deep
tendon reflexes .
 12 lead EKG revealed a wide QRS complex rhythm with a rate of 70-
100 bpm, QRS duration of 238 msec

5. Treatment
 Lidocaine bolus and infusion . Because her arrhythmia continued
unabated, she was initiated a procainamide infusion and
discontinued lidocaine .
 One hour after admission, the patient’s Serum K level was found to
be at 10.0 mEq/L. The procainamide infusion was discontinued .
 Went on Calcium, Insulin, Glucose were given intravenously
 Then, underwent emergent dialysis , potassium level gradually
returned to normal

7.  Cardiac enzymes were found to be within normal limits.
 A transthoracic echocardiogram revealed normal left ventricular
systolic function .
 She was discharged from the hospital in stable condition with no
further arrhythmias.
 The cause of her hyperkalemia was never ascertained; however, it
was postulated that there might have been an inappropriate
potassium concentration in her dialysis fluid.

8. What we have known about Potassium
and Heart
 Extracellular potassium concentration is normally maintained between
4.0 and 4.5 mEq/L.
 Ninety-five percent of total body potassium is intracellular; only 2% is
extracellular.
 A 70-kg man, for instance, has about 3,920 mEq of potassium in the
intracellular space but only 59 mEq in the extracellular space.
 Given that the total daily intake of potassium from a normal diet can be
up to 200 mEq.
Gettes LS. Effects of ionic changes on impulse propagation. In: Rosen MR, Janse MJ, Wit AL, editors. Cardiac electrophysiology: a
textbook. Mount Kisco (NY): Futura Publishing Co; 1990. p. 459–80.

9.  Total body potassium levels are regulated mostly by the kidneys,
with only 5% to 10% of ingested potassium excreted in the feces.
 When increased intake of potassium overwhelms the ability of the
kidneys to excrete potassium, or when a decrease in renal function
occurs, hyperkalemia may result.
 Because there are often no clinical signs or symptoms to suggest
hyperkalemia, clinicians must frequently rely on two or more clinical
information.

10.  Hyperkalemia is a common cause of the cardiac arrhythmias seen
in clinical practice.
 The challenge in managing hyperkalemia comes from the fact that
it can be difficult, if not impossible, to identify the condition solely on
the basis of electrocardiographic information.
 In a study performed at the University of Pittsburgh Medical Center,
only 46% of patients with potassium levels greater than 6.0 mEq/L
had electro-cardiographic changes, and only 55% of patients with
potassium levels greater than 6.8 mEq/L had changes consistent
with hyperkalemia.
Acker CG, Johnson JP, Palevsky PM, Greenberg A
Arch Intern Med. 1998 Apr 27; 158(8):917-24.

11.  Even when there is evidence of hyperkalemia on a patient's
electrocardiogram, physicians often miss the diagnosis.
 Wrenn and colleagues6 designed a study to determine the ability of
physicians to predict the presence of hyperkalemia solely on the basis of
their patients' electrocardiograms.
 The physicians in this study were able to predict hyperkalemia with a
sensitivity of 35% to 43% and a specificity of 85% to 86%. This small study
further emphasizes how difficult hyperkalemia can be to diagnose.
Nevertheless, hyperkalemia can manifest with classic
electrocardiographic changes that suggest its presence.
Tarail R. Relation of abnormalities in concentration of serum potassium to electrocardiographic disturbances. Am J Med 1948;5:828–37. [PubMed]
Szerlip HM, Weiss J, Singer I. Profound hyperkalemia without electrocardiographic manifestations. Am J Kidney Dis 1986;7:461–5

13. Effects of Hyperkalemia on Impulse Production
and Propagation
Illustration of a normal action potential (solid line) and the action potential as seen in the setting of
hyperkalemia (interrupted line). The phases of the action potential are labeled on the normal action
potential.

16. Curve relating Vmax to the resting membrane potential at the onset
of action potential. As the membrane potential becomes less
negative, as in the setting of hyperkalemia, the Vmax decreases,
leading to a depression of conduction through the myocardium

18. DiFrancesco D (2010): The role of the
funny current in pacemaker activity.
Circulation Research; 106:434-446.
Different ionic mechanisms for automaticity in
the SAN and His-Purkinje system. The ionic fluxes
underlying different phases of the cardiac action
potential are indicated for cells in the SAN and
His-Purkinje system. In the SAN, phase 4
automaticity is regulated by a mixture of ionic
currents including L-type and T-Type Ca currents,
decay of the time-dependent K currents, and
slow activation of a hyperpolarization-activated
nonselective current (If). In Purkinje fibers, phase
4 depolarization is due exclusively to slow
activation of If which produces a depolarizing
current that eventually overcomes the
hyperpolarizing influence of the background K
current (IK1).

19. Why increase extracellular potassium cause more
potassium leaves the myocyte
One of the potassium currents (Ikr), located on the myocyte cell
membrane, is mostly responsible for the potassium efflux seen during
phases 2 and 3 of the cardiac action potential.
For reasons that are not well understood, these Ikr currents are sensitive to
extracellular potassium levels, and as the potassium levels increase in the
extracellular space, potassium conductance through these currents is
increased so that more potassium leaves the myocyte in any given time
period
Roden DM, Lazzara R, Rosen M, Schwartz PJ, Towbin J, Vincent GM. Multiple mechanisms in the long-QT syndrome.
Current knowledge, gaps, and future directions. The SADS Foundation Task Force on LQTS. Circulation 1996;94:1996–
2012

20. Surface Electrocardiogram Manifestations of
Hyperkalemia
Hyperkalemia: ECG manifestations and clinical considerations.
Dittrich KL, Walls RM
J Emerg Med. 1986; 4(6):449-55

21. Causes of Hyperkalemia
 The most common are renal disease and the ingestion of
medications that predispose the patient to hyperkalemia.
 Medications known to cause hyperkalemia include angiotensin-
converting enzyme inhibitors, angiotensin-receptor blockers,
penicillin G, trimethoprim, spironolactone, succinylcholine,
alternative medicines, and heparin, to name just a few.
 In their study in a university setting, Acker and colleagues reported
that 75% of all patients with severe hyperkalemia had renal failure,
and 67% were taking a drug that predisposed them to
hyperkalemia.
 Other less common causes of hyperkalemia include massive
crushing injury with resultant muscle damage, large burns, high-
volume blood transfusions, human immunodeficiency virus infection,
and tumor lysis syndrome. In many patients, the cause of
hyperkalemia is multifactorial and never clearly defined
Orlando MP, Dillon ME, O'Dell MW. Heparin-induced hyperkalemia confirmed by drug rechallenge. Am J Phys Med Rehabil 2000;79:93–6.
Abassi ZA, Hoffman A, Better OS. Acute renal failure complicating muscle crush injury. Semin Nephrol 1998;18:558–65. Bostic O, Duvernoy WF.
Hyperkalemic cardiac arrest during transfusion of stored blood. J Electrocardiol 1972;5:407–9

23. Treatment of Hyperkalemia
 The treatment for hyperkalemia can be thought of in 3 distinct steps.
 First, antagonize the effects of hyperkalemia at the cellular level
(membrane stabilization).
 Second, decrease serum potassium levels by promoting the influx of
potassium into cells throughout the body.
 Third, remove potassium from the body.

24. Weisberg, Lawrence S. 2008.
Management of severe
hyperkalemia. Critical care
medicine, no. 12.
doi:10.1097/CCM.0b013e31818f222
b.
http://www.ncbi.nlm.nih.gov/pubm
ed/18936701.
Wrenn, K D, C M Slovis, and B S
Slovis. 1991. The ability of physicians
to predict hyperkalemia from the
ECG. Annals of emergency
medicine

26. Curve relating Vmax to the resting membrane potential under conditions of hyperkalemia
(solid line) and in the setting of increased calcium concentration (interrupted line). For any
given resting membrane potential, up to approximately −75

27. Transcellular ion movement. Most cells contain these pumps, antiporters, and channels. The effects of
insulin, catecholamines, and thyroid hormones on K transport are shown

28. Comparison of clinical studies of salbutamol
Excluded non-responders from analysis, †2.5 mg if <25 kg; 5 mg if >25 kg. IV = intravenous, Neb = nebulised

29. Potassium Removal from the Body
 The quickest, most efficient way to do this is through the use of
hemodialysis.
 In 1970, Morgan and colleagues reported the removal of 48 mEq/L of
potassium using a Kiil dialyzer over a 10-hour period; others confirmed
these findings.
 Because of the time, expense, and invasive nature of hemodialysis
therapy, it is rarely used as a 1st-line treatment for hyperkalemia unless a
patient is already on dialysis and has life-threatening hyperkalemia. For
most patients, treatment with an exchange resin such as sodium
polystyrene sulfonate is more appropriate
Hou S, McElroy PA, Nootens J, Beach M. Safety and efficacy of low-potassium dialysate. Am J Kidney Dis 1989;13: 137–43. [PubMed]
53. Sherman RA, Hwang ER, Bernholc AS, Eisinger RP. Variability in potassium removal by hemodialysis. Am J Nephrol 1986;6:284–8

30. sodium polystyrene sulfonate (SPS)
 SPS is the only cation-exchange resin currently available in the
United States, and it is not particularly well tolerated.
 In addition, the data show that much of its potassium-lowering
effects can be ascribed to an increase in stool volume
caused by sorbitol, with which it is frequently introduced
McCullough PA, Beaver TM, Bennett-Guerrero E, et al. Acute and chronic cardiovascular effects of hyperkalemia: new insights into
prevention and clinical management. Rev Cardiovasc Med. 2014;15:11-23. Abstract Kovesdy CP. Management of hyperkalaemia in
chronic kidney disease. Nat Rev Nephrol. 2014;10:653-662

31. Two new agents in development
 Patiromer* is a "designer" form of exchange resin that appears to be
much better tolerated than SPS.
 In fact, patiromer has been given on a regular basis, and initial
clinical trials tested whether it would enable greater use of RAAS
inhibitors and mineralocorticoid receptor antagonists.
 Later studies found it to be an effective therapy, vs placebo, for
both short- and long-term treatment of hyperkalemia
Tzamaloukas AH, Glew RH. Efficacy and safety of patiromer in prevention and treatment of hyperkalemia. J
Symptoms Signs. 2013;2:474-484

33. ZS-9
 ZS-9* is a zirconium silicate compound. It has a silica crystalline
structure designed to specifically bind potassium ions.
 Ammonium is the only other ion that binds significantly to ZS-9 --
potassium and ammonium are similar in terms of ionic radius. ZS-9 is
unique in that its specificity allows it to start binding potassium in the
small intestine, as opposed to the more terminal parts of the bowel
where potassium concentrations tend to be highest.
 This has always been a limitation with SPS because of competition
for binding between sodium and potassium; in the small intestine,
SPS binds almost no potassium because the concentration of
sodium is so high

38. What about the role of Bicap
 Sodium bicarbonate infusion can shift potassium from the
extracellular to intracellular space by increasing blood pH.
 However, routine bicarbonate therapy for the treatment of
hyperkalemia is controversial. In a study by Blumberg and
associates, 12 dialysis patients with potassium levels of 5.25 to 8.15
mEq/L received 390 mmol of intravenous sodium bicarbonate over
a 6-hour period.
 No change in potassium levels was seen until 4 hours after drug
administration, when a decrease of 0.7 mEq/L was noted; at 6 hours,
however, the decrease in potassium-um level was only 0.35 mEq/L
Effect of prolonged bicarbonate administration on plasma potassium in terminal renal failure. Blumberg A, Weidmann P, Ferrari P
Kidney Int. 1992 Feb; 41(2):369-74

39. .
.
Kim HJ. Combined eVect of bicarbonate and insulin with glucose in acute therapy of hyperkalemia in end-stage renal disease patients.
Nephron 1996;72:476–82.
Kim HJ. Acute therapy for hyperkalemia with the combined regimen of bicarbonate and beta(2)-adrenergic agonist (salbutamol) in
chronic renal failure patients. J Korean Med Sci 1997;12:111–16
Comparison of clinical studies of NaHCO3
Dose
Sample NaHCO3 Concentration Mean initial
size (mmol) (%) K (mmol/l)
8 120 8.4 6.4
5 90 1.4 4.23
10 240 8.4 5.66
10 120 1.4 5.83
9 2/kg 8.4 5.98

40.  Four studies examined the efficacy of NaHCO3 and all failed
to show any reduction in K within 60 minutes.
 These trials did not include patients with severe
hyperkalaemia or severe metabolic acidosis.
 Allon and Shanklin reported that NaHCO3 had no additive
effect on the action of insulin or salbutamol while Kim3
16reported that NaHCO3 increased the effect of insulin and
salbutamol. The patients in Kim’s studies had a higher initial
plasma K.
Kim HJ. Combined eVect of bicarbonate and insulin with glucose in acute therapy of hyperkalemia in
end-stage renal disease patients. Nephron 1996;72:476–82.
Kim HJ. Acute therapy for hyperkalemia with the combined regimen of bicarbonate and beta(2)-
adrenergic agonist (salbutamol) in chronic renal failure patients. J Korean Med Sci 1997;12:111–16

41. Take Home Message
 Hyperkalemia can still be very challenging to diagnose.
 Patients with severe hyperkalemia frequently have normal
electrocardiograms or electrocardiographic abnormalities that are
difficult to attribute to hyperkalemia.
 The diagnosis of hyperkalemia must be considered in any patient
with clinical risk factors that would predispose them to its
development.
 Sodium bicarbonate therapy has little use in the routine treatment of
hyperkalemia unless severe metabolic acidosis is present

42. THANK YOU