Clinical and electrophysiological consequences of hyperkalemia – NephrologyNews.com

Introduction

Hyperkalemia is a common electrolyte disorder, especially among patients along with chronic kidney disease (CKD), diabetes mellitus, or heart failure.^1–3 Hyperkalemia represents one of the crucial acute electrolyte abnormalities, because of its potential for causing life-threatening arrhythmias. Whereas hyperkalemia occurs relatively infrequently in people along with normal kidney function, hyperkalemia can easily be even more common in patients that have actually predisposing conditions. As discussed by Kovesdy,⁴ patients along with CKD are the most severely affected group by virtue of their diminished ability to excrete potassium. The problem is further aggravated by the superimposed additional predisposing conditions that regularly cluster within patients along with CKD. These include comorbidities (eg, congestive heart failure, diabetes mellitus) and a wide array of medications and herbal over-the-counter formulations.

Hyperkalemia is associated along with increased risk for all-cause mortality and for malignant arrhythmias such as ventricular fibrillation. The increased risk for side outcomes is observed even in serum potassium ranges that are usually not considered targets for therapeutic interventions. The heightened risk of mortality associated along with hyperkalemia is present in all patient populations, even in those in whom hyperkalemia occurs otherwise rarely, such as people along with normal kidney function.

In the following sections, we focus on two topics: 1) the clinical evaluation of the patient along with hyperkalemia, and 2) electrocardiographic manifestations of hyperkalemia.

Definition

Potassium, a metallic inorganic ion along with atomic weight of 39, is the most abundant cation in the body. The vast majority of potassium resides in the intracellular compartment, along with only a small quantity in the extracellular space. The “normal” range for serum potassium is regularly defined as from 3.five to 5.five mEq/L; however, plasma potassium is 0.five mEq/L lower. It is interesting to note that while total physique potassium is lower in females and in older patients, serum potassium concentration is independent of sex and age.

Technique for measuring serum potassium

Serum potassium is measured by the use of a flame photometer or ion-selective electrode. Even though the procedure is rapid, simple, and reproducible, caution is in order. In interpreting serum potassium, the clinician ought to be aware that because the intracellular potassium concentration is approximately 40-fold better compared to the extracellular concentration, any maneuver that would certainly result in the release of a small quantity of intracellular potassium in to the sample will certainly erroneously raise serum potassium. As detailed in Table 1, these include: a) tight tourniquet, b) vigorous workout of the extremity throughout blood drawing, c) hemolysis because of vigorous shaking of the test tube, d) thrombocytosis (platelet count > 600,000), and/or (e) leukocytosis (white blood-cell count > 200,000). In the latter two situations, the longer the blood stands, the better the rise in serum potassium will certainly be.

Clinical significance of minor deviations from the narrow normal range

The normal range for serum potassium is narrow (3.5–5.five mEq/L), and a minor departure from this range (by much less compared to 1.0 mEq/L) is associated along with substantial morbidity and mortality. Even though a 1.0 mEq modification in concentration is small in absolute terms, it profoundly changes the ratio of intracellular to extracellular potassium, sometimes by as much as 25%. Therefore, rapid evaluation and—as soon as indicated—treatment of both hypo- and hyperkalemia are critical. In the following sections we summarize the clinical consequence of hyperkalemia. These symptoms, signs, and laboratory findings ought to alert the clinician to the feasible existence of a substantial derangement in serum potassium.

Hyperkalemia is generally attributable to either intracellular shifts of potassium or impaired renal potassium excretion. Cell shifts account for transient enhances in serum potassium levels, whereas sustained hyperkalemia is generally caused by diminished renal potassium excretion. Impaired renal potassium excretion can easily be caused by a primary decrease in distal sodium delivery, a primary decrease in mineralocorticoid level or activity, or abnormal cortical compiling duct function. Excessive potassium intake is an infrequent cause of hyperkalemia as soon as renal function is intact, however the increased potassium intake can easily worsen the severity of hyperkalemia in the context of impaired renal excretion.

Before concluding that a cell shift or renal defect in potassium excretion is present, the physician should exclude pseudohyperkalemia (see Table 2).⁵ Pseudohyperkalemia is an in vitro phenomenon caused by the mechanical release of potassium from cells throughout the phlebotomy procedure or specimen processing. This diagnosis is made as soon as the serum potassium concentration exceeds the plasma potassium concentration by 0.five mEq/L (0.five mmol/L). As summarized in Table 1, common sets off include fist-clenching throughout the phlebotomy procedure, application of tourniquets, and use of small-bore needles.

Pathologic sets off of hyperkalemia are primarily encountered in the setting of hematologic disorders, such as thrombocytosis (platelets 500,000/cm³) and pronounced leukocytosis (leukocytes 70,000/cm³). Contamination along with potassium ethylenediaminetetraacetic acid (EDTA) in certain sampling tubes can easily cause a spurious increase in plasma potassium concentration accompanied by a rather reduced plasma calcium concentration.

The clinical evaluation of the patient along with hyperkalemia

Evaluation of the bodily examination

Patients along with hyperkalemia are regularly asymptomatic. as soon as present, the symptoms of hyperkalemia are nonspecific and predominantly related to muscular or cardiac function. The most common complaints are weakness and fatigue. Occasionally, a patient might complain of frank muscle paralysis or shortness of breath. Patients likewise might complain of palpitations or chest pain, or might report nausea, vomiting, and paresthesias. The patient’s history is most beneficial in identifying conditions that might predispose to the development of hyperkalemia.

The next step in the evaluation of the hyperkalemic patient is to obtain a thorough medical and dietary history. Is there evidence of excess dietary potassium intake? In the presence of normal renal and adrenal function, it is difficult to ingest sufficient potassium to overwhelm the normal renal excretory process and become hyperkalemic. In the setting of impaired kidney function, however, dietary intake usually is a contributor to hyperkalemia.

Dietary sources that are particularly enriched along with potassium include melons, citrus juice, and salt substitutes. others hidden sources of potassium reported to cause life-threatening hyperkalemia include raw coconut juice (potassium concentration, 44.3 mEq/L [44.3 mmol/L]) and noni juice (potassium, 5six mEq/L [56 mmol/L]).

For excessive potassium intake, patients ought to be queried concerning the following:

Eating disorders: rather unusual diets consisting almost exclusively of high-potassium foods, such as fruits (eg, bananas, oranges, melons), dried fruits, raisins, fruit juices, nuts, and vegetables along with little to no sodium.

“Heart-healthy and balanced diets”: Ironically, these could be incriminated. The rather low-sodium and high-potassium diets recommended for patients along with cardiac disease, hypertension, and diabetes mellitus might predispose patients to an increased risk of hyperkalemia.

Use of potassium supplements: In over-the-counter herbal supplements, sports drinks, dietary supplements such as noni (Morinda citrifolia) juice, salt substitutes, or prescribed pharmacologic agents

Laxative use: An additional interesting, surreptitious source of potassium is Movicol^® (Norgine BV, the Netherlands), a brand-name laxative that includes polyethylene glycol (macrogol) 3350. Macrogol 3350 is a widely used iso-osmotic laxative (likewise called MiraLAX^® Powder [Bayer AG, Leverkusen, Germany], or glycolax). Each packet of Movicol^® contains macrogol 3350, along with the addition of sodium bicarbonate, sodium chloride, and potassium chloride. It is crucial to note that each 13.8 g sachet of Movicol^® contains 46.six mg of potassium chloride (approximately 5.4 mmol/L). Electrolytes are included to tips mitigate the opportunity of electrolyte imbalance and dehydration. The materials of the sachets are mixed along with water to make a drink. Hyperkalemia is the most common reported electrolyte imbalance as a result of treatment along with macrogol laxative. In value terms, Movicol^® is currently the largest-selling laxative in the world. The point to be emphasized is that others macrogol powders could be “fortified” by additional potassium chloride.

When evaluating hospitalized patients, the physician ought to review the medication list for potassium supplements or high-dose penicillin G potassium, and review the chart to determine whether the patient has actually received transfusions. along with patients that have actually undergone cardiac surgery, the opportunity of residual effects of cardioplegic solutions ought to be considered.

When evaluating decreased potassium excretion, the physician ought to query patients concerning a history of renal insufficiency or renal failure. In addition, any history of diabetes mellitus or sickle-cell disease or trait, or symptoms of lower urinary tract obstruction, ought to be elicited. These conditions predispose patients to type IV renal tubular acidosis, likewise called hyperkalemic renal tubular acidosis.^6–8 Type IV renal tubular acidosis likewise might accompany others tubulointerstitial disorders, polycystic kidney disease, or amyloidosis.

Often, patients along with type IV renal tubular acidosis likewise have actually hyporeninemic hypoaldosteronism.^6,8–11  Patients along with ureteral diversion in to the ileum can easily make hyperkalemia because of reabsorption of secreted potassium.

The next step in the diagnostic evaluation: think about whether the hyperkalemia is the result of a cellular shift

Cellular redistribution is a a lot more crucial cause of hyperkalemia compared to of hypokalemia. Clinicians ought to understand that as little as a 2% shift in intracellular potassium to the extracellular fluid might result in a serum potassium level as higher as 8 mEq/L (8 mmol/L) (see Table 2). The major physiologic regulators of potassium shift in to cells are insulin and catecholamines.

Additional etiologies of hyperkalemia

Metabolic acidosis and hyperkalemia

It has actually been generally assumed that acidosis produces hyperkalemia as a result of shifts of potassium from the intracellular to the extracellular compartment. There is ample clinical and experimental evidence, however, to support the conclusion that uncomplicated organic acidemias do not create hyperkalemia.

Metabolic acidosis promotes potassium exit from cells depending on the type of acid present. Mineral acidosis (NH₄Cl or HCl), by virtue of the relative impermeability of the chloride anion, results in the greatest efflux of potassium from cells; whereas organic acidosis (ie, lactic, hydroxybutyric, or methylmalonic acid) results in no substantial efflux of potassium.

Patients along with diabetic ketoacidosis regularly are depleted of total-physique potassium as a result of renal potassium losses resulting from increased distal sodium delivery (the osmotic diuretic effect of glucose and excretion of sodium-ketoacid salts) occurring in the setting of higher aldosterone levels, which are stimulated by volume depletion.

Does the patient have actually a disturbance in renal potassium excretion?

Although redistribution of potassium can easily result in hyperkalemia, the increase in potassium levels is generally mild and not sustained. Hyperkalemia that is prolonged and severe implies the presence of impaired renal potassium excretion. Usually, the clinical setting will certainly allow the clinician to determine whether there is a disturbance in renal potassium excretion.

Drug-induced hyperkalemia

Drug-induced hyperkalemia is an crucial however regularly overlooked problem that is encountered typically in clinical practice, in the ambulatory as well as the impatient setting. Every evaluation of a hyperkalemic patient ought to include a careful review of medications to determine if a drug capable of causing or aggravating hyperkalemia is present. As detailed in Table 1, medications generally create hyperkalemia either by causing redistribution of potassium (β₂-adrenergic blockers, succinylcholine, digitalis overdose, hypertonic mannitol) or by impairing renal potassium excretion. Drugs cause impaired renal potassium excretion by 1) interfering along with the production and/or secretion of aldosterone (nonsteroidal anti-inflammatory drugs, angiotensin-converting enzyme inhibitors, angiotensin-II receptor antagonists, heparin, cyclosporine, and FK 506); or 2) blocking the kaliuretic effects of aldosterone (potassium-sparing diuretics, trimethoprim, pentamidine, and nafamostat mesilate).

A careful search for “hidden” potassium loads and for sets off of impaired tubular secretion of potassium (including drugs) is necessary. Finally, it is crucial to realize that the sets off of hyperkalemia could be additive. Patients might have actually a lot more compared to one cause of hyperkalemia at the same time. Therefore, all potential sets off of hyperkalemia, including drugs and surreptitious sources of potassium, ought to constantly be systematically evaluated in every hyperkalemic patient.^14,15

Interpretation of urinary electrolytes

Chronic disorders in potassium homeostasis are associated along with a defect in the cation’s handling by the kidney.⁵ The interpretation of urinary electrolyte values is helpful. First, it should be emphasized that there are no normal values for urinary potassium excretion. Rather, exactly what is crucial is whether the laboratory values are appropriate for the clinical setting. Normal subjects that are potassium-deprived might excrete as little as 10 to
1five mmol/day. In contrast, potassium excretion can easily attain levels of 200 mmol/day in response to a substantive increase in dietary potassium intake.¹² Nevertheless, determination of the transtubular potassium gradient (TTKG) is a popular tool among some clinicians to assess renal potassium handling. The TTKG is most beneficial in the evaluation of hyperkalemia as soon as the physician is attempting to discriminate between reduced aldosterone levels and aldosterone resistance.¹³

Electrocardiographic manifestations

Because potassium is essential for regulating the normal electrical activity of the heart, it is readily apparent that hyperkalemia can easily create changes in the electrocardiogram (EKG). Increased extracellular potassium reduces myocardial excitability, along with depression of both pacemaking and conducting tissues. along with progressive worsening, hyperkalemia leads to suppression of impulse generation by the sinoatrial node and reasonable conduction by the atrioventricular (AV) node and His-Purkinje system, thereby resulting in bradycardia and conduction blocks and, ultimately, cardiac arrest.^16,17

Table 3 summarizes the sequential stages of EKG changes induced by hyperkalemia, and Table 4 shows the different cell types susceptible to potassium-induced effects on myocardial conduction and contractility. The latter list explains well the differential observations that can easily be made from an electrophysiological point of view. The numerical limits for potassium concentrations offered in Table 3 along with regard to EKG alterations are, of course, estimates and not absolute values. As an example, potassium levels of about 8 mEq/L could already lead to cardiac arrest in the presence of co-medications and factors causing QT prolongation, additional electrolyte disorders (calcium, magnesium), or generally increased susceptibility of myocardial target cells or structures.^18–26

Indirect evidence on exactly how clinically and adversely meaningful hyperkalemia can easily be in dialysis patients came from the End-Stage Renal Disease Clinical Performance Measures Project demonstrating increased mortality, especially including cardiac arrest and dysrhythmia events toward the end of the long dialysis interval.²⁷ Even though no laboratory proof could be given (because of the nature of this analysis), one key feature of this post-dialysis phase is the presence of the highest probability for moderate to severe hyperkalemia. Elsewhere in this supplement, Epstein and Roy-Chaudhury review the pivotal role of electrolytes, especially hyperkalemia, in the pathogenesis of arrhythmias and sudden cardiac death on the patient being treated along with dialysis.²⁸

The earliest electrocardiographic manifestation associated along with “mild” hyperkalemia (serum potassium = 5.5–6.five mEq/L) might include tall, peaked, narrow-based T waves in precordial (V2–V4) leads and fascicular blocks (left anterior and left posterior fascicular blocks).²⁹ Moderate hyperkalemia (serum potassium between 6.five and
7.five mEq/L) could be associated along with first-degree AV block, decreased P-wave amplitude followed by disappearance of the P waves, and sinus arrest. ST segment depression and sometimes ST segment elevation simulating an acute myocardial infarction have actually likewise been described. Severe hyperkalemia (serum  potassium >7.five mEq/L) is manifested by atypical bundle branch block, intraventricular conduction delay, ventricular tachycardia, ventricular fibrillation, idioventricular rhythm, the “sine wave,” and asystole.

Several others electrocardiographic alterations might occur, including AV arrhythmias, pacemaker dysfunction, rate-dependent bundle branch block, AV block along with junctional rhythm, and pseudonormalization of inverted T waves.

The concomitant use of others medications might likewise be of importance. Mild hyperkalemia, for instance, has actually been associated along with junctional bradycardia in patients on verapamil.³⁰ Even though typical EKG manifestations of hyperkalemia are a lot more most likely in the presence of severe hyperkalemia, it is crucial to note that the characteristic EKG changes described are not constantly present, even in patients along with severe hyperkalemia.^22–24 Conversely, others factors, in addition to serum potassium levels, modify the EKG manifestations of hyperkalemia (see Table 5).

It is essential as soon as treating hyperkalemia that the whole clinical picture is taken in to account, Pretty compared to simply the numerical potassium values. Further, EKG changes have actually reduced sensitivity in identifying people along with hyperkalemia or predicting severity.^31,32 Among patients along with end-stage renal disease, a population at particularly higher risk for hyperkalemia, differences in calcium levels might contribute to the predictive value of the EKG in detecting hyperkalemia.^22,24 Older age and the presence of diabetes have actually likewise been associated along with a lower likelihood of hyperkalemia-induced peaked T waves.

Conclusions

Hyperkalemia is a common electrolyte disorder, especially among patients along with CKD, diabetes mellitus, or heart failure. Hyperkalemia represents one of the crucial acute electrolyte abnormalities, because of its potential for causing life-threatening arrhythmias. In this information we have actually reviewed two aspects of hyperkalemia: 1) a suggested approach to the clinical evaluation of the patient along with hyperkalemia, and 2) electrocardiographic manifestations of hyperkalemia. We have actually reviewed an approach to the clinical evaluation of the patient along with hyperkalemia. We have actually likewise emphasized that drug-induced hyperkalemia is an crucial however regularly overlooked problem encountered typically in clinical practice, and have actually given examples of surreptitious sources of potassium that might promote hyperkalemia.

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