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Hyperkalemia Case Discussion
(Below case is discussed assuming you’ve completed the recommended readings – if you haven’t yet, please do so prior to continuing)
Part One
DM is an 81 year old female in the ED accompanied by her daughter. Chief complaint is decreased oral intake, confusion, and
lethargy for one day, reports medication compliance and missed dialysis x1.
PMH
-End Stage Renal Disease
-Diabetes Type 2
-cirrhosis
-hypertension
-Hyponatremia
-Hepatic encephalopathy
Home Meds
Allopurinol
Aspirin
Ciprofloxacin
Darbopoetin
Furosemide
Insulin glargine
Insulin lispro
Rifaximin
Allergies
Codeine
PCN
Narcotic analgesics
Labs drawn earlier in the day by hospice nurse include:
Hb (i-STAT)
HCT (i-STAT)
WBC
RBC
Hb
PLT
11.9 g/dL
35 %
9.91 thousand/microL
3.64 million/microL
12.0 g/dL
92 thousand/microL
Na (i-STAT)
133 mEq/L
K (i-STAT)
5.5 mEq/L
Cl (i-STAT)
112 mEq/L
Total CO2 (POC) 13 mEq/L
AG (POC)
15 mmol/L
Glucose(POC)
421 mg/dL
BUN(i-STAT) (POC)
104 mg/dL
Cr (POC)
4.0 mg/dL
Ca (Ionized) (POC)
1.60 mmol/L
Questions for Discussion:
What about this case stands out to you? Given the patient complaint, medical history, and medication list,
discuss appropriate pharmaceutical considerations. What would be appropriate follow up questions and
information?
Case Discussion Part One
With DM’s presentation and vague complaints the differential is wide. Initial labs, detailed history and physical
assessment will help the team evaluate concern for possibilities such as hepatic encephalopathy, hypoglycemia,
UTI, medication interactions or even meningitis. We will want to clarify the extent of her renal disease and her
glycemic profile as well as her current electrolytes, fluid status and infectious concerns. Working closely with a
multidisciplinary team is vital to narrowing down DM’s differential, but even at this early stage she
demonstrates some classic signs of electrolyte disturbance worthy of evaluation.
First, DM’s history of renal disease should immediately make us question her potassium balance – the kidney is
responsible for clearing 80% of the body’s potassium load(note?), so whenever you think of kidney injury you
should think of hyperkalemia and whenever you see hyperkalemia you should wonder about renal function.
Her current serum creatinine should allow us to estimate a GFR, although we can also ask if DM is on dialysis,
and if so, when her last dialysis session was. Other common causes of hyperkalemia include: (list)…The
presence of any of these factors should bring to mind the possibility of hyerpkalemia or any possible
contributing role.
For DM, we see from her history of diabetes and her home med use that she has access to insulin introducing
the possibility of hypoglycemia, and - given the role that insulin plays in potassium balance – hypokalemia.
DM’s reported lab values would appear to rule out hypokalemia, although without knowing we can wonder
simultaneously about hypoglycemia and hypokalemia.
DM’s history of cirrhosis, hyponatremia, and furosemide all put her at risk for hyponatremia, both acute and
chronic. Her current status of altered mental status makes this possibility even more of a concern.
Part Two
DM continues to demonstrate altered mental status. Heart rate is 60 bpm, SBP 120, DBP 80, RR 22 bpm, Temp
36.7. DM is described as “confused but directable”. A repeat panel was run:
K 6.7 mEq/L
CO2 12 mEq/L
Na 130 mEq/L
Anion Gap 12
Cl 144 mEq/L
Glucose 322 mg/dL
BUN 110 mg/dL
Cr 4.2 mg/dL
An EKG was run showing the following findings when compared to previous EKGs: concern for ST elevations, QRS 148, Vent rate 59.
Questions for Discussion:
Why was a repeat panel run? What about these results is concerning — are these labs what you
expected? Why was the EKG run? What is the significance of comparing the EKG to previous EKGs and
what is the significance of the EKGfindings? What additional information would you like at this point? Is this
a critical situation? What would you do next?
Case Discusion Part Two
The labs we see in Part One don’t fully explain the clinical picture - DM’s sodium level may appear marginally
low until we notice that her glucose is significantly elevated. Hyperosmolarity resulting from hyperglycemia
can falsely lower sodium levels necessitating a correction equation: (1.7 x [(Blood Glucose-100)/100]) to reach
a corrected sodium level of 138 which is within normal. It’s also not unusual to encounter significantly low
sodium levels in the setting of cirrhosis/hepatic encephalopathy. DM’s potassium is borderline/mildly elevated
but not enough to explain what we are seeing, and is lower than we might expect given end stage renal failure
and missed dialysis. DM’s anion gap is elevated with a low CO2 suggesting a possible metabolic acidosis, but
her glucose level is lower than we might typically expect in frank DKA. In order to truly understand lab
values, we need to know when they were drawn and how they were run? Intralab and interlab variation are
always consideration, and critical labs requiring action should always be questioned, particularly if they don’t
match your clinical picture. If the initial labs for DM were drawn in the morning then these labs may no longer
reflect DM’s actual panel. We would want to know if DM’s symptoms have worsened since these labs were
drawn. Acute changes in sodium can play a significant role in obtundation, but potassium is also susceptible to
dramatic changes in short period of times. This is partially due to the continuous active transport of potassium
between intracellular and extracellular. Because potassium is the primary intracellular cation, it is susceptible
to falsely elevated lab values, or pseudohyperkalemia. This can happen when red blood cells lyse either as a
result of difficulty drawing the sample, difficulty handling the test tube once drawn, or mishandling at any point
in the process. Potassium from inside the cell rushes out and produces falsely elevated levels, often in the arena
of 6.0 to 8.0. This phenomenon can also be seen in patients with dramatically elevated platelet levels
(>1,000,000/cm3) or dramatically elevated white blood cell counts (>70,000/cm3). For this reason elevated
potassium should always be confirmed with a redraw, particularly in the absence of any signs and symptoms
common to hyperkalemia. For this reason, and given an initial potassium level of 5.5 from the hospice nurse
and the subsequent potassium level of 6.7, we should probably draw one more potassium level to confirm the
elevated potassium.
While we’re waiting for this final potassium redraw, however, we are faced with the question of whether or not
to treat her apparent hyperkalemia. If we seek to aggressively lower her potassium and the redraw comes back
at 4.0, then we run the risk of inadvertently pushing DM into hypoglycemia. But if we fail to treat, DM may
become more symptomatic while we wait. To help us with our decision making, we ask ourselves if DM is
demonstrating classic signs and symptoms of hyperkalemia. DM is confused, which is more often associated
with sodium abnormalities, but it is certainly possible to see with potassium abnormalities, along with
descending paralysis in more severe hyperkalemia. More concerning with hyperkalemia is cardiac toxicity, so
at the first suspicion of hyperkalemia an EKG should be run. The extracellular/intracellular potassium gradient
is responsible for cardiac repolarization. Because such an overwhelming percentage of the body’s potassium is
intracellular (98%), even small changes in extracellular potassium can have dramatic effects on cardiac
repolarization leading to some fairly predictable EKG signs:
Getting an EKG for DM can help confirm any suspicions of hyperkalemia. It is important to note, however,
that the progression and/or severity of EKG changes do not always directly correlate with the serum
potassium. In other words, the EKG of a patient with a potassium of 6.5 may look worse than that of a
someone else with a K of 7.0. It is important to compare your current EKG to a prior, non-hyperkalemic
EKG for appropriate interpretation.
As potassium levels rise and repolarization slows, we can begin to see P waves flatten and heart rate slow down,
as we see with DM. At potassium levels above 5.5, we may see peaked “tented” T waves, generally in several
contiguous leads, and notable peaked compared to previous non-hyperkalemic EKGs. Prolonged PR waves
may also be seen. As Potassium levels exceed 6.5 we may see loss of P wave. QRS complexes > 120ms, as we
see in DM, are of particular concern, especially if previous EKGs show a normal QRS complex. Potassium
levels greater than 8 are often accompanied by dramatic EKG changes and should be considered lifethreatening. Levels greater than 8 with normal EKG changes should raise questions about the veracity of the
potassium level, but treatment should be initiated while recheck is pending.
Part Three
Potassium was redrawn and DM received Calcium Gluconate 9mEq while results were being posted. Redraw confirmed K of 6.7
mEq/L. Point of care glucose showed blood sugar of 300mg/dL and DM was given 5 units of regular insulin iv, 50ml D50W, 50mEq
sodium bicarbonate, 3 amps of albuterol and 30 gm kayexolate. Nephrology was consulted, DM was admitted to medicine service
with diagnosis of hyperkalemia in the setting of chronic kidney disease and plans for dialysis in the morning.
Questions for Discussion:
Discuss the rationale and appropriateness for DM’s treatments, along with alternatives and controversies in
hyperkalemia management.
Case Discussion Part Three
Hyperkalemia results from either a high potassium intake, a transcellular potassium shift, or - as we see with
DM - decreased potassium excretion. Potassium excretion alterations most often occur due to decreased renal
function, as we see in DM, although it can also be caused by medications that interfere with aldosterone like
spironolactone and epleronone, calcineurin antagonists like cyclosporine, Bactrim, heparin, and – often
overlooked – potassium supplements. Even if DM’s EKG was perfectly normal, potassium levels above 6 are
considered risk for “impending” EKG changes, so treatment should be initiated. The safest approach to initial,
pre-confirmatory treatment is one that would protect (“stabilize”) cardiac tissue from the toxic effects of
potassium without putting DM at risk for hypoglycemia in the event that her potassium was in fact falsely
elevated.
Calcium
The agent used most commonly to stabilize the myocardium is Calcium, either as the gluconate or the chloride
salt. The onset is rapid, with normalization of EKG often seen within minutes of calcium infusion; if 2gm of
calcium gluconate is infused without symptom resolution, it is reasonable to repeat a dose. DM received 2 g
calcium gluconate (9 mEq) with prompt effects – her QRS quickly normalized, her heart rate increased
and her peaked T waves resolved. Calcium’s stabilization lasts for 30-60 minutes, so if symptoms return at
this point redosing is required. When giving calcium infusion we must consider calcium gluconate versus
calcium chloride. Calcium chloride has the benefit of containing more elemental calcium. One gram of
calcium gluconate contains 4.5 mEq of calcium, while 1 gm of calcium chloride contains 13.6 mEq.
Calcium chloride is also widely available in code carts in the form of a prefilled syringe. However,
calcium chloride is considerably irritating upon administration and can cause significant tissue damage if
extravasated. Calcium gluconate is much safer to administer and is generally the preferred agent – 1 to
2gm is often given with good effect. Calcium chloride is best saved for life threatening situations such as
systole or impending torsades. Of note, there are case reports of patients on digoxin experiencing digoxin
toxicity immediately after receiving iv calcium, but causality is uncertain; iv calcium is generally
considered safe even in patients receiving digoxin if the calcium is diluted and given over 15-30 minutes.
Consideration should be made in patients actively experiencing digoxin toxicity – some practitioners
advocate using magnesium in these patients, although data is limited. Note that Calcium will protect the
myocardium from potassium’s toxic effects but will not decrease potassium levels at all. This makes it
ineffective as monotherapy, but safe to administer to DM while we are waiting for her conformation
draw.
Shift
Once DM’s hyperkalemia is confirmed we begin treatment aimed at reducing potassium levels. The first
phase of this treatment is “Shifting”, utilizing agents to shift potassium from the extracellular
environment to intracellular. Insulin is often the first agent used for this purpose. ATPase dependent NaK pumps located in liver and skeletal muscle shift potassium into cells in the presence of insulin and/or
adrenergic agonists. 10 units of insulin will usually decrease serum potassium by 0.5-1.0 mEq/L
although hypoglycemia becomes a consideration. In renal failure patients clear insulin at a slower rate
and run a higher risk of hypoglycemia, so patients with eGFR<30 ml/min often receive 5 units of insulin,
as we see in DM. Similar to insulin, adrenergic agonists (albuterol is the preferred agent in hyperkalemia
management) will work on the Na-K-ATPase pump and drive potassium back into the cell and can be
effective in the acute treatment setting by lowering potassium 0.5-1.0 mEq/L within 30 minutes with a
duration of action of at least 2 hours. There is evidence that some patients are resistant to albuterol’s
hypokalemic effect, so albuterol is discouraged as monotherapy and is more appropriate as part of a
combined treatment approach where it’s been shown to exhibit an additive effect with insulin to reduce
serum potassium. In order to achieve an effective dose, 10-20mg of nebulized albuterol should be given –
note that this is a much higher dose than often seen but is necessary for effect.
Dextrose
Dextrose is often given as part of the hyperkalemia protocol in part to stimulate endogenous production
of insulin, but moreover to protect the patient from the hypoglycemic effect of administered insulin. For
DM we have two considerations – first of all, dextrose is not always necessary in patients with glucose
levels greater than 300 mg/dL so we might argue against giving dextrose in DM. However, patients with
decreased renal function are at increased risk of hypoglycemia due to impaired renal clearance of insulin.
When CrCl decreases below 30ml/min, insulin clearance can be dramatically prolonged while dextrose
metabolism is not impaired at all; patients in renal failure receiving a single amp of dextrose will often
clear the dextrose within 20-30 minutes while the hypoglycemic effect of insulin will continue up to 60
minutes after administer. For this reason, many euglycemic patients receiving 10 units insulin and 25gm
dextrose will become significantly hypoglycemic within 30-40 minutes of administration. While patients
with initial glucose levels above 300mg/dL may not require any dextrose at all, patients with normal
glucose levels will require much more than one amp of dextrose ; any appropriate management requires
blood glucose monitoring every 20-30 minutes for at least 1 hour following insulin administration. Many
protocols address the risk of hypoglycemia by infusing D10W after insulin administration, or by
preparing insulin drips in a solution of D10W.
Sodium Bicarbonate
Once a mainstay of treatment, NaHCO3 was theorized to push potassium into the cell by using a sodiumhydrogen exchange pump. Unfortunately, several studies have failed to show a strong effect for NaHCO3,
and bicarb therapy has largely fallen out favor. Some clinicians reserve its use for patients with
hyperkalemia and acidemia, where the Na+/H+ exchanger required is more likely to be in an active mode.
Limited data suggest a potential additive effect with insulin but overall mixed data suggests that sodium
bicarbonate should never be used as monotherapy and is best employed in a combined approach for
severely acidotic patients. One might argue that sodium bicarbonate was not clearly indicated in DM, but
many clinicians would suggest that if bicarb is to be given, it is better to give in an infusion of 150mEq/L
than in a 50 mEq push such as DM received.
Sodium Polystyrene Sulfonate
Cation exchange resins like SPS or Kayexalate exchange sodium for potassium, with 30g of SPS potentially
removing 120mEq of potassium. SPS should theoretically increase the amount of potassium in stool, and
is often mixed with sorbitol to induce osmotic diarrhea. This is not a fast way of decreasing serum
potassium, and multiple studies have shown the potassium reducing effects of SPS to be equal to those of
other non-resin cathartics. Many clinicians point to the lack of evidence in acute cases as a reason to
avoid SPS, along with the risk of GI necrosis. Most studies find them to work slowly over a 24 hour
period. However, as in the case of DM, it is often used along with other treatments as a means of
eliminating potassium from the body. DM received kayexolate orally although it can also be given
rectally – either way SPS should be used cautiously and only when necessary.
Loop Diuretics
Loop diuretics such as furosemide can be used in patients capable of producing urine, and is an often
overlooked mechanism of eliminating potassium. Diuresis may take 15 minutes (IV) or longer (PO)
depending on the perfusion of the kidneys.
Dialysis
Dialysis is the quickest, most efficient way to remove potassium from the patient’s body. Due to the
invasive nature it is reserved for patients already on dialysis with severe hyperkalemia, patients who can
often be refractory to traditional hyperkalemia treatments. For these patients dialysis can substantially
drop serum potassium levels and (1-1.5meq/L/hr) and is a reasonable first line treatment.
For DM’s follow up care, we should further consider continuous cardiac monitoring and serum potassium
redraws every 1-4 hours until potassium levels stabilize. Once DM is out of the acute care window we
can further pursue ongoing causes of hyperkalemia and means of preventing further hyperkalemia
episodes.