Hyperkalemia present.

Similarly, during increased potassium

release from endogenous sources, such as high cell
turnover or tissue damage, hyperkalemic states are
ESSENTIALS OF DIAGNOSIS
transient, unless concomitant renal pathology is
 Serum [K] above 5.0 mEq/L.
present. Chronic hyperkalemia is always associated
 Acute or chronic renal failure is the most with renal potassium excretion defects. It should be
common cause. noted that frequently multiple etiologies present
 Transcellular shift of K from the intracellular simultaneously and may obscure the picture.
to the extracellular space.
 Inhibition of the endocrine sequence. 1.1. Pseudohyperkalemia (fictitious
hyperkalemia)
Abstract Pseudohyperkalemia commonly arises from shifts
This article focuses on the pathogenesis, clinical of potassium from blood cells to blood plasma by
manifestations, and various treatment modalities mechanical trauma during venipuncture or during
for acute hyperkalemia and presents a systematic the clotting process in vitro. These effects are
approach to selecting a treatment strategy. further enhanced when there is marked
Hyperkalemia, a life-threatening condition caused leukocytosis or thrombocytosis. A rare form of
by extracellular potassium shift or decreased renal pseudohyperkalemia, familial pseudohyperkalemia,
potassium excretion, usually presents with non- causes potassium to leak out of excessively
specific symptoms. Early recognition of moderate permeable erythrocyte membranes in vitro. In vivo,
to severe hyperkalemia is vital in preventing fatal however, this disorder does not contribute to
cardiac arrhythmias and muscle paralysis. hyperkalemia because the leaked potassium is
Management of hyperkalemia includes the renally excreted (1, 2).
elimination of reversible causes (diet, medications),
rapidly acting therapies that shift potassium into 1.2. Decreased renal excretion
cells and block the cardiac membrane effects of The kidney has a central role in normal potassium
hyperkalemia, and measures to facilitate removal of homeostasis with the distal components of the
potassium from the body (saline diuresis, oral nephron responsible for the bulk of potassium
binding resins, and hemodialysis). Hyperkalemia excretion. The renal abnormalities that manifest in
with potassium level more than 6.5 mEq/L or EKG hyperkalemia can be grouped as follows: renal
changes is a medical emergency and should be tubular secretory abnormalities, impaired renin-
treated accordingly. Treatment should be started aldosterone axis, drug-induced hyperkalemia,
with calcium gluconate to stabilize cardiomyocyte decreased distal tubular flow with low sodium, and
membranes, followed by insulin injection, and b- renal failure.
agonists administration. Hemodialysis remains the
most reliable method to remove potassium from the 1.2.1. Renal tubular secretory abnormalities
body and should be used in cases refractory to Common renal tubular secretory abnormalities that
medical treatment. Prompt detection and proper can lead to hyperkalemia are type 1 (distal) renal
treatment are crucial in preventing lethal outcomes. tubular acidosis, renal disease in sickle cell disease
and systemic lupus erythematosus, renal transplant,
Keywords: hyperkalemia, review, treatment, and obstructive uropathy.
potassium, hyperkalemic
1.2.2. Impaired renin-aldosterone axis
1. Pathogenesis of Hyperkalemia Impaired renin-aldosterone axis can cause
The basic pathophysiology of hyperkalemic states enhanced hyperkalemia. This occurs in Addison's
involves either extracellular potassium shifts or disease, adrenal enzyme deficiencies (21
decreased renal excretion. Common etiologies hydroxylase, corticosterone methyl oxidase),
leading to measurement of hyperkalemia include hyporeninemic hypoaldosteronism, and angiotensin
pseudohyperkalemia, decreased renal excretion, deficiency or insensitivity. Furthermore,
and abnormal potassium distribution. Increased medications can impair the renin-aldosterone axis,
dietary potassium intake or other exogenous including prostaglandin inhibitors (indomethacin,
sources rarely cause more than transient ibuprofen, piroxicam, aspirin, naproxen,
hyperkalemic states unless underlying pathology is
fenoprofen, and sulindac), beta-adrenergic hypertonicity from hyperglycemia enhances
antagonists, angiotensin-converting enzyme hyperkalemia. Hypoaldosteronism, in addition to
inhibitors (ACEI), angiotensin receptors blockers diminishing renal potassium excretion, causes
(ARB), tacrolimus, and heparin. decreased uptake of potassium by non-renal cells.
On the other hand, catecholamines and beta-agonist
1.2.3. Drug-induced hyperkalemia enhance potassium uptake by cells via the beta-2
In addition to interfering with the renin-aldosterone adrenergic receptors on cells, and when these
axis, medications can cause hyperkalemia by other receptors are unavailable due to antagonist actions,
mechanisms. Potassium-sparing diuretics hyperkalemia occurs. However, administration of
(amiloride and triamterene), trimethoprim, and propranolol causes out of proportion hyperkalemia
pentamidine all block sodium reabsorption in the due to potassium efflux from muscles combined
distal nephron, reducing the luminal voltage with its antiadrenergic effects. There can also be a
gradient, and decreasing potassium excretion rates. rise in extracellular potassium during significant
Spironolactone blocks aldosterone receptors, and tissue damage, and if accompanied by acute kidney
cyclosporine causes hyperkalemia by enhancing injury, hyperkalemia will be sustained. Other
chloride reabsorption. causes of hyperkalemia from potassium shifts
include severe exercise, hyperkalemic periodic
1.2.4. Decreased distal tubular flow with low paralysis, cardiac surgery, insulin antagonists
sodium (somatostatin and diazoxide), hypertonic solutions
A significant decrease in sodium delivery and/or (hypertonic saline and hypertonic mannitol),
tubular flow rate at the distal nephron also causes digitalis overdose, succinylcholine, arginine
hyperkalemia. These are commonly seen in patients hydrochloride, lysine hydrochloride, and fluoride
with either underlying renal disease or Addison's poisoning (1, 2).
disease, who may develop acute pulmonary edema
or have intravascular volume depletion. When the etiology of hyperkalemia is not apparent,
an assessment of renal potassium excretion by
1.3. Renal failure measuring urine osmolality and spot potassium
Acute tubular necrosis and interstitial nephritis are levels to determine the transtubular potassium
the common causes of oliguric acute kidney failure. gradient [TTKG=(urine K/serum K)/(Urine
The distal tubules and collecting duct cells are osmolality/Serum osmolality) can help clarify the
often damaged and thus unable to excrete cause. Hyperkalemia with a TTKG of >7 suggests
potassium. Additionally, as explained above, the normal aldosterone function and that renal tubular
distal delivery of sodium and/or the distal tubular mechanisms for potassium excretion are intact.
flow rate is often decreased, once again causing This may be seen in the setting of decreased filtrate
hyperkalemia. In chronic kidney disease (CKD), delivery to the distal nephron with volume
the diminished tubular mass is less tolerant to acute depletion. A TTKG <7 suggests impaired
potassium challenges; therefore, these patients are potassium secretion secondary to
at increased risk for developing hyperkalemia (1, hypoaldosteronism. Measurement of the serum
2). aldosterone level will distinguish adrenal disease or
hyporeninemic hypoaldosteronism from
1.4. Abnormal potassium distribution aldosterone resistance.
Distribution abnormalities of potassium are seen
during metabolic acidosis, insulin deficiency, Table 1. Hyperkalemia
aldosterone deficiency, adrenergic antagonists, and
Renal retention
tissue damage. During metabolic acidosis, there is a
 Acute renal failure
significant extracellular shift of intracellular
 Chronic renal failure (especially interstitial renal
potassium in exchange for protons leading to
disease)
hyperkalemia. Insulin also maintains potassium  Drugs (see text)
balance between extracellular and intracellular  Addison's disease
compartments, and decrease in insulin causes a rise  Renal tubular acidosis Type IV
in extracellular potassium (commonly seen in  Pseudohypoaldosteronism
diabetic patients). Furthermore, serum
 Tissue release and transcellular shifts of K
 Tissue breakdown (hemolysis, rhabdomyolysis,
ischemia, tumor lysis)
 Insulin deficiency
 Hyperosmolarity
 Hyperchloremic metabolic acidosis
 Drugs (succinylcholine, digoxin toxicity)

2. Diagnosis
The initial diagnostic approach begins with the
clinical history, review of medications, and
physical examination. Symptoms and signs include
muscular weakness or flaccid paralysis, ileus, and
characteristic electrocardiograph (ECG) changes
Figure 2. Prominent T waves and widened QRS complex
(Figure 121). Laboratory tests should be directed of hyperkalemia
towards causes suggested by the history and
physical examination, with attention to serum
electrolytes, creatinine, and blood urea nitrogen. A
spot urine test for potassium, creatinine, and
osmoles should be obtained to calculate the
fractional excretion of potassium and the
transtubular potassium gradient (Table 422,23). Figure 3. Sine wave pattern in untreated hyperkalemia –
The transtubular potassium gradient is an this rhythm is termed the sinoventricular rhythm. Most
assessment of renal potassium handling, with a often, this rhythm has a slow ventricular response.
normal value of eight to nine, rising at times to 11
after an increase in potassium intake. Values lower
than five in the face of hyperkalemia suggest an
inappropriate renal response to high potassium22; a
very low value suggests hypoaldosteronism.

Figure 4. ECG of a patient with an elevated potassium

level of 7.5mEq/dl; this is another example of the
sinoventricular rhythm of severe hyperkalemia – in this
case, the ventricular response is more rapid

Figure 1. Hyperpotassemia: P-wave absent

 Box 1. Sinoventricular rhythm and severe hyperkalemia

Sinoventricular rhythms are generated in the setting of

severe hyperkalemia.

Appearance of the rhythm

 Absolute serum level of potassium is not directly
related to rhythm’s development.
 Rapidity and chronicity of the serum potassium
elevation are related to rhythm’s development;
rapid increase and/or new onset of hyperkalemia
are more likely seen with this rhythm.

Figure 5. Suggested management issues based on ECG Causes of hyperkalemia

findings in a patient with hyperkalemia.  Renal dysfunction (acute kidney injury and
chronic renal failure)
 Severe, end-stage liver disease
Sinoventricular Rhythm of Severe  Severe, end-stage heart failure
Hyperkalemia  Potassium-sparing diuretic and other medications
Sinoventricular rhythm (Figure 8.6) is a very  Excessive potassium replacement
specific rhythm that is related to severe  Salt substitute (potassium chloride) use
hyperkalemia (Box 8.3), the clinical syndrome
involving significantly elevated serum potassium Management goals
levels. The rhythm originates from the SA node;  Stabilization of cardiac cell membrane: calcium
yet, owing to the presence of extremely high levels  Internal shifting of potassium intracellularly:
of extracellular potassium, the atrial myocardium insulin, glucose, sodium bicarbonate, magnesium
does not generate a detectable depolarization; thus, sulfate, and albuterol; impact is transient in nature,
this rhythm does not generate a P wave lasting 20–40min
on the surface ECG. Further, conduction through  Removal of potassium from the body: gut-binding
the AV node is also impaired; thus, a ventricular resins, hemodialysis
pacemaker assumes control with regard to impulse
generation and conduction. Further conduction 3. Treatment
delay in the ventricles leads to additional widening It is better to prevent hyperkalemia than to treat it.
of the QRS complex. The resulting rhythm has a A careful review of patient medications, diet, and
rate of usually 50–60 bpm – although it can present in particular over-the-counter drugs (NSAIDs) is
with markedly faster or slower rates. The QRS mandatory. Hidden sources of K, such as herbal
complex is quite wide and, if untreated, will further medicines, sports drinks, and salt substitutes, must
widen, ultimately assuming the appearance of a be sought. The recent demonstration that
sine wave. Asystole or ventricular fibrillation will aldosterone antagonists provide a survival benefit
soon follow. to patients with congestive heart failure (who are
usually also taking ACEI and/or ARB drugs plus -
blockers) has generated a major increase in the
prevalence of hyperkalemia among these patients.
When hyperkalemia is acute and severe, emergency
intervention is necessary. Treatment options for
acute and severe hyperkalemia include the
following:
Figure 6. Sinoventricular rhythm of severe 1) Direct reversal of cardiotoxic effects with
hyperkalemia. The QRS complex is very broad without intravenous calcium.
evidence of P waves; the rhythm is usually slow and 2) Translocating K into cells:
regular. (a) Widened QRS complex; (b) widened QRS a. Insulin infusion—with glucose if
complex with sine wave configuration of the QRS
appropriate.
complex.
b. 2-Adrenergic agonists such as albuterol.
 c. NaHCO3 infusion. c. Via dialysis for patients with severe acute
3) Increasing K excretion: or chronic renal failure.
a. Via the kidney by ECF volume expansion
and kaliuretic diuretics.
b. Via the gastrointestinal tract by inducing
diarrhea and K-binding resins.

Gambar 1. Guide to the treatment of hyperkalemia.

Treatment of acute hyperkalemia, regardless of the EKG changes (Table 1). The goal
regardless of its causes, depends on potassium of acute therapy is to stabilize the cardiomyocyte
level, and presence or absence of EKG changes membranes to prevent arrhythmia, shift potassium
(Fig. 1). Emergent treatment should be into the cells, and enhance elimination of potassium
administered if EKG changes are present or if from the body.
plasma potassium level is more than 6.5 mEq/L

Tabel 1. Emergency management of acute hyperkalemia

Medication Response Dosage Onset of Duration of Mechanism Expected decrease in

type action action of action potassium level
Calcium Immediat 10 to 20 mL Immediat Can worsen Protects
gluconate e of 10 e digoxin toxicity myocardium
percent from toxic
solution IV effects of
over two to calcium; no
three effect on
minutes serum
potassium
level
Insulin Regular
insulin 10
units IV
with 50 mL
 of 50
percent
glucose
Albuterol 10 to 20 mg
(Ventolin) by nebulizer
over 10
minutes (use
concentrated
form, 5 mg
per mL)
Furosemide 20 to 40 mg
(Lasix) IV, give
with saline
if volume
depletion is
a concern
Sodium Oral: 50 g in
polystyrene 30 mL of
sulfonate sorbitol
(Kayexalate) solution
Rectal: 50 g
in a
retention
enema

Long-term therapy of hyperkalemia

includes diet and medication modifications. A low
potassium diet should be discussed with the patient,
once the acute issues are resolved. Medications
should be reevaluated with special attention paid to
ACEI, ARB, and potassium-sparing diuretics.

Daftar Pustaka
1. Mushiyakh, Y., Dangaria, H., Qavi, S., Ali, N.,
Pannone, J., & Tompkins, D. (2012).
Treatment and pathogenesis of acute
hyperkalemia. Journal of community hospital
internal medicine perspectives, 1(4),
10.3402/jchimp.v1i4.7372.
https://doi.org/10.3402/jchimp.v1i4.7372