| Hyperkalemia | |
|---|---|
| Other names | Hyperkalaemia |
 | |
| Electrocardiography showingprecordial leads in hyperkalemia. | |
| Pronunciation | |
| Specialty | Critical care medicine,nephrology |
| Symptoms | Palpitations,muscle pain,muscle weakness,numbness[1][2] |
| Complications | Cardiac arrest[1][3] |
| Causes | Kidney failure,hypoaldosteronism,rhabdomyolysis, certain medications[1] |
| Diagnostic method | Blood potassium > 5.5 mmol/L,electrocardiogram[3][4] |
| Differential diagnosis | Pseudohyperkalemia[1][2] |
| Treatment | Medications, low potassium diet,hemodialysis[1] |
| Medication | Calcium gluconate,dextrose withinsulin,salbutamol,sodium bicarbonate[1][3][5] |
| Frequency | ~2% (people in hospital)[2] |
Hyperkalemia is an elevated level ofpotassium (K+) in theblood.[6][1] Normal potassium levels are between 3.5 and 5.0 mmol/L (3.5 and 5.0 mEq/L) with levels above 5.5 mmol/L defined as hyperkalemia.[3][4] Typically hyperkalemia does not cause symptoms.[1] Occasionally when severe it can causepalpitations,muscle pain,muscle weakness, ornumbness.[1][2] Hyperkalemia can cause anabnormal heart rhythm which can result incardiac arrest and death.[1][3]
Common causes of hyperkalemia includekidney failure,hypoaldosteronism, andrhabdomyolysis.[1] A number of medications can also cause high blood potassium including mineralocorticoid receptor antagonists (e.g.,spironolactone,eplerenone andfinerenone)NSAIDs,potassium-sparing diuretics (e.g.,amiloride),angiotensin receptor blockers, andangiotensin converting enzyme inhibitors.[1] The severity is divided into mild (5.5 – 5.9 mmol/L), moderate (6.0 – 6.5 mmol/L), and severe (> 6.5 mmol/L).[3] High levels can be detected on anelectrocardiogram (ECG),[3] though the absence of ECG changes does not rule out hyperkalemia.[6] The measurement properties of ECG changes in predicting hyperkalemia are not known.[6] Pseudohyperkalemia, due to breakdown ofcells during or after taking the blood sample, should be ruled out.[1][2]
Initial treatment in those with ECG changes is salts, such ascalcium gluconate orcalcium chloride.[1][3] Other medications used to rapidly reduce blood potassium levels includeinsulin withdextrose,salbutamol, andsodium bicarbonate.[1][5] Medications that might worsen the condition should be stopped, and a low-potassium diet should be started.[1] Measures to remove potassium from the body include diuretics such asfurosemide, potassium-binders such aspolystyrene sulfonate (Kayexalate) andsodium zirconium cyclosilicate, andhemodialysis.[1] Hemodialysis is the most effective method.[3]
Hyperkalemia is rare among those who are otherwise healthy.[7] Among those who are hospitalized, rates are between 1% and 2.5%.[2] It is associated with an increased mortality, whether due to hyperkalaemia itself or as a marker of severe illness, especially in those withoutchronic kidney disease.[8][7] The wordhyperkalemia comes fromhyper- 'high' +kalium 'potassium' +-emia 'blood condition'.[9][10]
The symptoms of an elevated potassium level are generally few and nonspecific.[11] Nonspecific symptoms may include feeling tired, numbness, and weakness.[11] Occasionally,palpitations and shortness of breath may occur.[11][12][13] Hyperventilation may indicate a compensatory response tometabolic acidosis, which is one of the possible causes of hyperkalemia.[14] Often, however, the problem is detected during screeningblood tests for a medical disorder, or after hospitalization for complications such ascardiac arrhythmia orsudden cardiac death. High levels of potassium (> 5.5 mmol/L) have been associated with cardiovascular events.[14]
Decreased kidney function is a major cause of hyperkalemia. This is especially pronounced inacute kidney injury where the glomerular filtration rate and tubular flow are markedly decreased, characterized byreduced urine output.[14] This can lead to a dramatically elevated potassium in conditions of increased cell breakdown, as the potassium is released from the cells and cannot be eliminated in the kidneys. Inchronic kidney disease, hyperkalemia occurs as a result of reduced aldosterone responsiveness and reduced sodium and water delivery in distal tubules.[15]
Medications that interfere with urinary excretion by inhibiting therenin–angiotensin system are one of the most common causes of hyperkalemia. Examples of medications that can cause hyperkalemia includeACE inhibitors,angiotensin receptor blockers,[14] non-selectivebeta blockers, andcalcineurin inhibitor immunosuppressants such asciclosporin andtacrolimus.[16] For potassium-sparingdiuretics, such asamiloride andtriamterene; both the drugs block epithelial sodium channels (ENaC) in the collecting tubules, thereby preventing potassium excretion into urine.[15]Spironolactone acts by competitively inhibiting the action of aldosterone.[14]NSAIDs such asibuprofen,naproxen, orcelecoxib inhibitprostaglandin synthesis, leading to reduced production of renin and aldosterone, causing potassium retention.[17] The antibiotictrimethoprim and theantiparasitic medicationpentamidine inhibits potassium excretion, which is similar to mechanism of action by amiloride and triamterene.[18]
Mineralocorticoid (aldosterone) deficiency or resistance can also cause hyperkalemia. Primary adrenal insufficiency are:Addison's disease[19] andcongenital adrenal hyperplasia (CAH) (including enzyme deficiencies such as21α hydroxylase,17α hydroxylase,11β hydroxylase, or3β dehydrogenase).[20]
Metabolic acidosis can cause hyperkalemia as the elevated hydrogen ions in the cells can displace potassium, causing the potassium ions to leave the cell and enter the bloodstream. However, inrespiratory acidosis or organic acidosis such aslactic acidosis, the effect on serum potassium is much less significant, although the mechanisms are not completely understood.[15]
Insulin deficiency can cause hyperkalemia as thehormoneinsulin increases the uptake of potassium into the cells. Hyperglycemia can also contribute to hyperkalemia by causinghyperosmolality in extracellular fluid, increasing water diffusion out of the cells, and causing potassium to move alongside water out of the cells. The co-existence of insulin deficiency, hyperglycemia, and hyperosmolality is often seen in those affected bydiabetic ketoacidosis. Apart from diabetic ketoacidosis, other causes that reduce insulin levels, such as the use of the medicationoctreotide, and fasting, which can also cause hyperkalemia. Increased tissue breakdown such asrhabdomyolysis,burns, or any cause of rapid tissuenecrosis, includingtumor lysis syndrome can cause the release of intracellular potassium into blood, causing hyperkalemia.[14][15]
Beta2-adrenergic agonists act on beta-2 receptors to drive potassium into the cells. Therefore,beta blockers can raise potassium levels by blocking beta-2 receptors. However, the rise in potassium levels is not marked unless other co-morbidities are present. Examples of drugs that can raise the serum potassium are non-selective beta-blockers such aspropranolol andlabetalol. Beta-1 selective blockers such asmetoprolol do not increase serum potassium levels.[15][medical citation needed]
Exercise can cause a release of potassium into the bloodstream by increasing the number of potassium channels in the cell membrane. The degree of potassium elevation varies with the degree of exercise, which ranges from 0.3 meq/L in light exercise to 2 meq/L in heavy exercise, with or without accompanying ECG changes or lactic acidosis. However, peak potassium levels can be reduced by prior physical conditioning, and potassium levels are usually reversed several minutes after exercise.[15] High levels ofadrenaline andnoradrenaline have a protective effect on the cardiac electrophysiology because they bind to beta 2 adrenergic receptors, which, when activated, extracellularly decrease potassium concentration.[21]
Hyperkalemic periodic paralysis is anautosomal dominant clinical condition where there is a mutation in the gene located at 17q23 that regulates the production of proteinSCN4A. SCN4A is an important component ofsodium channels in skeletal muscles. During exercise, sodium channels normally open to allow the influx of sodium into the muscle cells fordepolarization to occur. But in hyperkalemic periodic paralysis, sodium channels are slow to close after exercise, causing excessive influx of sodium and displacement of potassium out of the cells.[15][22]
Rare causes of hyperkalemia are discussed as follows. Acute digitalis overdose, such asdigoxin toxicity, may cause hyperkalemia[23] through the inhibition of sodium-potassium-ATPase pump.[15] Massiveblood transfusion can cause hyperkalemia, especially in infants and patients with low glomerular filtration rate (GFR, a measure of kidney function) due to leakage of potassium out of the red blood cells during storage.[15] Givingsuccinylcholine to people with conditions such as burns, trauma, infection, prolonged immobilisation can cause hyperkalemia due to widespread activation of acetylcholine receptors rather than a specific group of muscles.Arginine hydrochloride is used to treatrefractory metabolic alkalosis. The arginine ions can enter cells and displace potassium out of the cells, causing hyperkalemia. Calcineurin inhibitors such ascyclosporine,tacrolimus,diazoxide, andminoxidil can cause hyperkalemia.[15]Box jellyfish venom can also cause hyperkalemia.[24]
Excessive intake of potassium is not a primary cause of hyperkalemia because, in the presence of normal kidney function and the absence of drugs causing alterations in homeostasis, the kidney responds to the rise in potassium levels by increasing the excretion of potassium into urine. This is mediated byaldosterone hormone secretion and by increasing the number of potassium-secreting channels in kidney tubules.[15] Acute hyperkalemia in infants is also rare, even though their body volume is small, with accidental ingestion of potassium salts or potassium medications. Hyperkalemia usually develops when there are other co-morbidities such ashypoaldosteronism andchronic kidney disease.[15]
Pseudohyperkalemia occurs when the measured potassium level is falsely elevated.[25] Mechanical trauma during blood drawing can cause potassium leakage out of the red blood cells due tohaemolysis of the blood sample.[25] Fist clenching during the blood draw can cause a rise in potassium levels in the venous blood as it is sampled; this difference may be as much as 1 mmol/L.[26][27] Differences of this order of magnitude cause problems (false positive results for clinically-important hyperkalemia) for patients with low glomerular filtration rate (GFR; a measure of kidney function), type IV renal tubular acidosis (RTA), or on evidence-based medication for cardio-renal risk (RASi, MRAs). The practice, widespread in laboratories in North America, should be discontinued. Prolonged storage of blood samples or agitation in transit is also associated with red cell lysis that can increase serum potassium levels. Hyperkalemia may become apparent when a person's platelet concentration is more than 500,000/microL in a clotted blood sample (serum blood sample). Potassium leaks out of platelets after clotting has occurred. A high white cell count (greater than 120,000/microL) in people withchronic lymphocytic leukemia increases the fragility of red blood cells, thus causing pseudohyperkalemia during blood processing. This problem can be avoided by processing serum samples, because clot formation protects the cells from haemolysis during processing. A familial form of pseudohyperkalemia, a benign condition characterised by increased serum potassium in whole blood stored at cold temperatures, also exists. This is due to increased potassium permeability in red blood cells.[15]
Potassium is the most abundantintracellularcation. About 98% of the body's potassium is found inside cells, with the remainder in theextracellular fluid, including the blood. Membrane potential is maintained principally by theconcentration gradient and membrane permeability to potassium, with some contribution from theNa+/K+ pump. The potassium gradient is critically important for many physiological processes, including maintenance of cellularmembrane potential,homeostasis of cell volume, and transmission ofaction potentials innerve cells.[14]
Potassium is eliminated from the body through thegastrointestinal tract,kidney andsweat glands. In the kidneys, elimination of potassium is passive (through theglomeruli), and reabsorption is active in theproximal tubule and the ascending limb of theloop of Henle. There is active excretion of potassium in thedistal tubule and thecollecting duct; both are controlled byaldosterone. In sweat glands, potassium elimination is quite similar to the kidney; its excretion is also controlled by aldosterone.[6]
Regulation of serum potassium is a function of intake, appropriate distribution between intracellular and extracellular compartments, and effective bodily excretion. In healthy individuals, homeostasis is maintained when cellular uptake and kidney excretion naturally counterbalance a patient's dietary intake of potassium.[28][29] When kidney function becomes compromised, the ability of the body to effectively regulate serum potassium via the kidney declines. To compensate for this deficit in function, the colon increases its potassium secretion as part of an adaptive response. However, serum potassium remains elevated as the colonic compensating mechanism reaches its limits.[30][31]
Hyperkalemia develops when there is excess production (oral intake, tissue breakdown) or ineffective elimination of potassium. Ineffective elimination can be hormonal (in aldosterone deficiency) or due to causes in the kidney that impair excretion.[32]
Increased extracellular potassium levels result indepolarization of the membrane potentials of cells due to the increase in theequilibrium potential of potassium. This depolarization opens some voltage-gatedsodium channels, but also increases the inactivation at the same time. Since depolarization due to concentration change is slow, it never generates an action potential by itself; instead, it results inaccommodation. Above a certain level of potassium, the depolarization inactivates sodium channels, opens potassium channels, thus the cells becomerefractory. This leads to the impairment of neuromuscular,cardiac, andgastrointestinal organ systems. Of most concern is the impairment of cardiac conduction, which can causeventricular fibrillation and/orabnormally slow heart rhythms.[14]
To gather enough information for diagnosis, the measurement of potassium must be repeated, as the elevation can be due tohemolysis in the first sample. The normal serum level of potassium is 3.5 to 5 mmol/L. Generally, blood tests forkidney function (creatinine,urea),glucose and occasionallycreatine kinase andcortisol are performed. Calculating thetrans-tubular potassium gradient has been recommended as a method of identifying whether or not aldosterone is acting; however, the measurement properties of this test were never described and some experts doubt the usefulness of this approach.[6]
In themedical history, the presence of knownkidney disease,diabetes mellitus, and the use of certainmedications (e.g.,potassium-sparing diuretics) are important issues.[14]Electrocardiography (ECG) may be performed to determine if there are ECG changes, tachy- or brady-arrythmias.[14]
Normal serum potassium levels are generally considered to be between 3.5 and 5.3mmol/L.[3] Levels above 5.5 mmol/L generally indicate hyperkalemia, and those below 3.5 mmol/L indicatehypokalemia.[1][3]
With mild to moderate hyperkalemia, there may be prolongation of the PR interval and development of peakedT waves.[14] The measurement properties (sensitivity and specificity) of ECG to predict laboratory hyperkalemia, or to predict more severe arrhythmia in the context of hyperkalemia, are not known. Severe hyperkalemia results in a widening of theQRS complex, and theECG complex can evolve to asinusoidal shape.[33] There appears to be a direct effect of elevated potassium on some of the potassium channels that increases their activity and speeds membrane repolarisation. Also, (as notedabove), hyperkalemia causes an overall membrane depolarization that inactivates many sodium channels. The faster repolarisation of the cardiacaction potential causes the tenting of the T waves, and the inactivation of sodium channels causes a sluggish conduction of the electrical wave around the heart, which leads to smaller P waves and widening of the QRS complex.[medical citation needed] Some of the potassium currents are sensitive to extracellular potassium levels, for reasons that are not well understood. As the extracellular potassium levels increase, potassium conductance is increased so that more potassium leaves the myocyte in any given period.[34] To summarize, classic ECG changes associated with hyperkalemia are seen in the following progression: peaked T wave, shortened QT interval, lengthened PR interval, increased QRS duration, and eventually absence of the P wave with the QRS complex becoming a sine wave. Bradycardia, junctional rhythms and QRS widening are particularly associated with increased risk of adverse outcomes[35]
The serum potassium concentration at which electrocardiographic changes develop is somewhat variable. Although the factors influencing the effect of serum potassium levels on cardiac electrophysiology are not entirely understood, the concentrations of otherelectrolytes, as well as levels of catecholamines, play a major role.[medical citation needed]
ECG findings are not a reliable finding in hyperkalemia. In a retrospective review, blinded cardiologists documented peaked T-waves in only 3 of 90 ECGs with hyperkalemia.Sensitivity of peaked-Ts for hyperkalemia ranged from 0.18 to 0.52, depending on the criteria for peak-T waves.[medical citation needed]
Preventing recurrence of hyperkalemia typically involves reduction of dietary potassium, removal of an offending medication, and/or the addition of adiuretic (such asfurosemide orhydrochlorothiazide).[14] Sodiumpolystyrene sulfonate andsorbitol (combined as Kayexalate) are occasionally used on an ongoing basis to maintain lower serum levels of potassium, though the safety of long-term use of sodium polystyrene sulfonate for this purpose is not well understood.[14]
High dietary sources include meat, chicken, seafood,vegetables such asavocados,[36][37]tomatoes andpotatoes, fruits such asbananas,oranges and nuts.[38]
Emergency lowering of potassium levels is needed when new arrhythmias occur at any level of potassium in the blood, or when potassium levels exceed 6.5 mmol/L. Several agents are used to temporarily lower K+ levels. The choice depends on the degree and cause of the hyperkalemia, and other aspects of the person's condition.
Calcium (calcium chloride orcalcium gluconate) increasesthreshold potential through a mechanism that is still unclear, thus restoring normal gradient between threshold potential and resting membrane potential, which is elevated abnormally in hyperkalemia. A standard ampule of 10% calcium chloride is 10 mL and contains 6.8 mmol of calcium. A standard ampule of 10% calcium gluconate is also 10 mL but has only 2.26 mmol of calcium. Clinical practice guidelines recommend giving 6.8 mmol for typical EKG findings of hyperkalemia.[14] This is 10 mL of 10% calcium chloride or 30 mL of 10% calcium gluconate.[14] Though calcium chloride is more concentrated, it is caustic to the veins and should only be given through a central line.[14] Onset of action is less than one to three minutes and lasts about 30–60 minutes.[14] The goal of treatment is to normalise the EKG, and doses can be repeated if the EKG does not improve within a few minutes.[14]
Some textbooks suggest that calcium should not be given in digoxin toxicity as it has been linked to cardiovascular collapse in humans and increased digoxin toxicity in animal models. Recent literature questions the validity of this concern.[medical citation needed]
Several medical treatments shift potassium ions from the bloodstream into the cellular compartment, thereby reducing the risk of complications. The effect of these measures tends to be short-lived, but may temporarily alleviate the problem until potassium can be removed from the body.[39]
Severe cases requirehemodialysis, which is the most rapid method of removing potassium from the body.[40] These are typically used if the underlying cause cannot be corrected swiftly while temporising measures are instituted or there is no response to these measures.
Loop diuretics (furosemide,bumetanide,torasemide) andthiazide diuretics (e.g.,chlortalidone,hydrochlorothiazide, orchlorothiazide) can increase kidney potassium excretion in people with intact kidney function.[40]
Potassium can bind to a number of agents in the gastrointestinal tract.[43][29] Sodiumpolystyrene sulfonate (Kayexalate) was approved for this use decades ago, and can be given by mouth or rectally.[40] Sodium polystyrene sulfonate given with sorbitol was uncommonly but convincinglyassociated withcolonicnecrosis; this combination is no longer used.[44][45][46]
Patiromer is taken by mouth and works by binding freepotassium ions in thegastrointestinal tract and releasingcalcium ions for exchange, thus lowering the amount of potassium available for absorption into the bloodstream and increasing the amount lost via the feces.[14][47] The net effect is a reduction of potassium levels in the blood serum.[14]
Sodium zirconium cyclosilicate is a medication that bindspotassium in thegastrointestinal tract in exchange for sodium and hydrogen ions.[14] Onset of effects occurs in one to six hours.[48] It is taken by mouth.[48]
Hyperkalemia is rare among those who are otherwise healthy.[7] Among those who are in the hospital, rates are between 1% and 2.5%.[2]
In the United States, hyperkalemia is induced bylethal injection inpeople condemned to death by the state.Potassium chloride is the last of the three drugs administered and actually causes death.
Cyclosporine may reduce potassium excretion by altering the function of several transporters, decreasing the activity of the renin-angiotensin-aldosterone system, and impairing tubular responsiveness to aldosterone
In children, hypoaldosteronism can result from a deficiency of enzymes required for aldosterone synthesis