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Volume 33, Number 1, 200640 Hyperkalemia Revisited

Review Hyperkalemia RevisitedHyperkalemia is a common clinical condition that can induce deadly cardiac arrhythmias.

Electrocardiographic manifestations of hyperkalemia vary from the classic sine-wave

rhythm, which occurs in severe hyperkalemia, to nonspecific repolarization abnormali-

ties seen with mild elevations of serum potassium. We present a case of hyperkalemia,

initially diagnosed as ventricular tachycardia, to demonstrate how difficult hyperkalemia

can be to diagnose. An in-depth review of hyperkalemia is presented, examining theelectrophysiologic and electrocardiographic changes that occur as serum potassium lev-

els increase. The treatment for hyperkalemia is then discussed, with an emphasis on the

mechanisms by which each intervention lowers serum potassium levels. An extensive

literature review has been performed to present a comprehensive review of the causes

and treatment of hyperkalemia. (Tex Heart Inst J 2006;33:40-7)

yperkalemia is a common clinical condition that can induce deadly cardiacarrhythmias. Electrocardiographic manifestations of hyperkalemia var yfrom the classic sine-wave rhythm, which occurs in severe hyperkalemia,

to nonspecific repolarization abnormalities seen with mild elevations of serumpotassium. Herein, we describe the clinical electrocardiographic abnormalities as-

sociated with hyperkalemia and present an in-depth review of the literature regard-ing its treatment.

Case Report

A 69-year-old woman with end-stage renal disease experienced the sudden onset ofcrampy abdominal pain and emesis several hours after a routine hemodialysis treat-ment. Severe fatigue and dysphoria followed, which prompted her to summonemergency medical personnel for assistance. She was taken to the local emergencydepartment, where she continued to have severe fatigue but denied chest pain, pal-pitations, dyspnea, pre-syncopal symptoms, fever, or additional gastrointestinaldiscomfort. The patients medications at the time of admission included omepra-zole, glipizide, labetalol, doxepin, quinine, phenergan, lactulose, aspirin, and seve-

lamer. Her medical history included long-standing diabetes mellitus, hypertension,and end-stage renal disease that had necessitated dialysis for the past 4 years.

Physical examination of the patient in the emergency department revealed awoman with ashen skin who was in moderate distress. Her blood pressure was141/87 mmHg with a pulse of 100 beats/min. She was breathing 32 times/minwith an oxygen saturation of 97% on 3 liters of oxygen via nasal cannula. On car-diovascular examination, heart sounds were inaudible. Her lung fields were clearto auscultation bilaterally, and results of the abdominal examination were normal.The extremities were without cyanosis or edema. Neurologically, she was alert andoriented, with diminished deep tendon reflexes.

Results of multiple 12-lead electrocardiograms revealed a wide QRS complexrhythm with a rate of 70 to 100 beats/min and a QRS duration of 238 msec, whichled to a diagnosis of ventricular tachycardia (Fig. 1). The patient was subsequently

treated with a lidocaine bolus and infusion. Because her arrhythmia continued un-abated, we initiated a procainamide infusion and discontinued the lidocaine. Onehour after admission, the patients serum potassium level was found to be at 10.0mEq/L. The procainamide infusion was discontinued; and calcium, insulin, glu-cose, and bicarbonate were given intravenously. She then underwent emergent dial-ysis and her potassium level gradually returned to normal.

After dialysis, her electrocardiographic results returned to baseline, with a QRSduration of 95 msec (compared with 238 msec at presentation; see Fig. 2), and hercardiac enzymes were found to be within normal limits. A transthoracic echocar-diogram revealed normal left ventricular systolic function, and she was discharged

Walter A. Parham, MDAli A. Mehdirad, MD, FACCKurt M. Biermann, BSCarey S. Fredman, MD, FACC

Key words:Albuterol;calcium; electrocardiog-raphy; electrophysiology;glucose; hemodialysis;hyperkalemia; insulin; ionexchange resins; potassiumtoxicity; sodium bicarbonate

From:Divisions ofCardiology (Drs. Fredman,Mehdirad, Parham; and Mr.Biermann) and Critical CareMedicine (Dr. Parham),Department of InternalMedicine, St. LouisUniversity School ofMedicine and St. JohnsMercy Medical Center,St. Louis, Missouri 63110

Address for reprints:Walter A. Parham, MD,St. Louis University School

of Medicine, Departmentof Internal Medicine,Division of Cardiology,3635 Vista Ave., FDT 13,St. Louis, MO 63110

E-mail:[email protected]

2006 by the Texas Heart

Institute, Houston

H

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overwhelms the ability of the kidneys to excrete po-tassium, or when a decrease in renal function occurs,hyperkalemia may result. Because there are often noclinical signs or symptoms to suggest hyperkalemia,clinicians must frequently rely on clinical information(that is, a history of renal failure or the ingestion ofmedications known to cause hyperkalemia), laborato-ry data, and electrocardiographic changes to make thediagnosis.

Hyperkalemia is a common cause of the cardiac ar-rhythmias seen in clinical practice. The challenge inmanaging hyperkalemia comes from the fact that itcan be difficult, if not impossible, to identify the con-dition solely on the basis of electrocardiographic infor-mation. Patients who present with hyperkalemia mayhave a normal electrocardiogram or have changes thatare so subtle that physicians frequently have diff icul-ty attributing these changes to increased potassiumlevels. In a study performed at the University of Pitts-burgh Medical Center, only 46% of patients with po-

tassium levels greater than 6.0 mEq/L had electro-cardiographic changes, and only 55% of patients withpotassium levels greater than 6.8 mEq/L had changesconsistent with hyperkalemia.2 In fact, there have beenseveral reports in the literature of patients who hadpotassium levels greater than 7.5 mEq/L with no elec-trocardiographic manifestations of hyperkalemia.3- 5

Even when there is evidence of hyperkalemia on a pa-tients electrocardiogram, physicians often miss thediagnosis. Wrenn and colleagues6 designed a study todetermine the ability of physicians to predict the pres-ence of hyperkalemia solely on the basis of their pa-tients electrocardiograms. The physicians in this study

were able to predict hyperkalemia with a sensitivity of35% to 43% and a specificity of 85% to 86%. Thissmall study further emphasizes how difficult hyper-kalemia can be to diagnose. Nevertheless, hyperka-lemia can manifest with classic electrocardiographicchanges that suggest its presence.

Effects of Hyperkalemia on

Impulse Production and Propagation

Potassium and sodium concentrations in the intracel-lular and extracellular compartments play a vital rolein the electrophysiologic function of the myocardium.Concentration gradients are established across the

myocyte membrane secondary to very high intracel-lular potassium concentrations and a relative paucityof potassium ions in the extracellular space. The op-posite is true of sodium ions, which are abundant ex-tracellularly and relatively few intracellularly. Theseconcentration gradients are maintained by sodium-potassium adenosine triphosphatase (Na-K ATPase)pumps on the cellular wall, which actively pump sodi-um out of the myocyte and potassium inward. Theseconcentration gradients establish an electrical poten-

from the hospital in stable condition with no furtherarrhythmias. The cause of her hyperkalemia was neverascertained; however, it was postulated that there mighthave been an inappropriate potassium concentration in

her dialysis fluid.

Discussion

Extracellular potassium concentration is normallymaintained between 4.0 and 4.5 mEq/L by a complexinterplay of potassium excretion and consumption.Ninety-five percent of total body potassium is intra-cellular; only 2% is extracellular. A 70-kg man, forinstance, has about 3,920 mEq of potassium in theintracellular space but only 59 mEq in the extracellu-lar space.1 Given that the total daily intake of potas-sium from a normal diet can be up to 200 mEq, one

can see how precisely and quickly the body must beable to respond to any given potassium load in orderto prevent severe hyperkalemia.

Total body potassium levels are regulated mostly bythe kidneys, with only 5% to 10% of ingested potassi-um excreted in the feces.1 Renal excretion of potas-sium is determined by the rate of potassium filtrationacross the glomerular basement membrane and by therate of its secretion and resorption in the distal tubulesof the nephron. When increased intake of potassium

Texas Heart Institute Journal Hyperkalemia Revisited 41

Fig. 1 Admission electrocardiogram.

Fig. 2 Electrocardiogram after the correction of hyperkalemia.

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tial across the cell membrane, leading to a restingmembrane potential of 90mV. The potassium gradi-ent across the cellular membrane is the most impor-tant factor in establishing this membrane potential;therefore, any changes in extracellular potassium con-centration may have profound effects upon myocyteelectrophysiologic function.7 For instance, as potassi-um levels increase in the extracellular space, the mag-nitude of the concentration gradient for potassiumacross the myocyte diminishes, thus decreasing theresting membrane potential (that is, 90 mV to 80mV; see Fig. 3).

Phase 0 of the action potential occurs when voltage-gated sodium channels open and sodium enters themyocyte down its electrochemical gradient (Fig. 3).The rate of rise of phase 0 of the action potential (Vmax)is directly proportional to the value of the restingmembrane potential at the onset of phase 0.7-9 This isbecause the membrane potential at the onset of depo-larization determines the number of sodium channels

activated during depolarization, which in turn deter-mines the magnitude of the inward sodium currentand the Vmax of the action potential. As illustrated inFigure 4, Vmax is greatest when the resting membranepotential at the onset of the action potential is approx-imately 75 mV, and does not increase as the mem-brane potential becomes more negative. Conversely,as the resting membrane potential becomes less neg-ative (that is, 70 mV), as in the setting of hyper-kalemia (Fig. 3), the percentage of available sodiumchannels decreases. This decrease leads to a decre-ment in the inward sodium current and a concurrentdecrease in the Vmax; therefore, as the resting mem-

brane potential becomes less negative in hyperkale-mia, Vmax decreases. This decrease in Vmax causes a slow-ing of impulse conduction through the myocardium

and a prolongation of membrane depolarization; as aresult, the QRS duration is prolonged.

As previously discussed, increasing the extracellularpotassium concentration results in a decrease in theresting membrane potential (that is, from 90 mV to80 mV). In turn, the threshold potential decreases(that is, from 75 mV to 70 mV); this 5-mV de-crease, however, is less than the decrease in resting po-tential. Therefore, the difference between the restingand threshold potentials decreases to approximately10 mV (as opposed to 15 mV in a physiologic milieu).

As potassium levels increase further, the resting mem-brane potential continues to become less negative,and thus progressively decreases Vmax. The changes inthreshold potential now parallel the changes in restingpotential, and the difference between the two reachesa constant value of approximately 15 mV. The de-crease in Vmax levels causes a slowing of myocardialconduction, manifested by progressive prolongationof the P wave, PR interval, and QRS complex. Insummary, the early effect of mild hyperkalemia onmyocyte function is to increase myocyte excitabilityby shifting the resting membrane potential to a lessnegative value and thus closer to threshold potential;

but as potassium levels continue to rise, myocyte de-pression occurs and Vmax continues to decrease.

Hyperkalemia also has profound effects upon phase2 and phase 3 of the action potential. After the rapidinflux of sodium across the cell membrane in phase 0,potassium ions leave the cell along its electrochemicalgradient, which is reflected in phase 1 of the actionpotential. As the membrane potential reaches 40 to45 mV during phase 0, calcium channels are stim-ulated, allowing calcium to enter the myocyte. The


Fig. 3 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. Note the decrease in

both the resting membrane potential and the rate of phase 0

of the action potential (Vmax) seen in hyperkalemia. Phase 2 and

3 of the action potential have a greater slope in the setting of

hyperkalemia compared with the normal action potential.

Fig. 4 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.

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these electrocardiographic changes are due to hyper-kalemia, and not to bundle branch disease, is that inhyperkalemia the conduction delay persists through-out the QRS complex and not just in the initial orterminal portions, as seen in left and right bundlebranch block, respectively.11,16As potassium levelsreach 8 to 9 mEq/L, sinoatrial (SA) node activity maystimulate the ventricles without evidence of atrialactivity, producing a sinoventricular rhythm. Thisoccurs because the SA node is less susceptible to theeffects of hyperkalemia and can continue to stimulatethe ventricles without evidence of atrial electrical ac-tivity.11,17 The electrocardiographic manifestations ofcontinued SA node function in the absence of atrialactivity may be very similar to those of ventriculartachycardia, given the absence of P waves and a wid-ened QRS complex (Fig 1).

As the hyperkalemia worsens and the potassium lev-els reach 10 mEq/L, sinoatrial conduction no longeroccurs, and passive junctional pacemakers take over

the electrical stimulation of the myocardium (acceler-ated junctional rhythm).11,12,18 If hyperkalemia contin-ues unabated, the QRS complex continues to widenand eventually blends with the T wave, producing theclassic sine-wave electrocardiogram. Once this occurs,ventricular fibrillation and asystole are imminent.

In addition to the previously mentioned arrhyth-mias, many other electrocardiographic abnormalitieshave been associated with hyperkalemia. In patientswith acutely elevated serum potassium levels, a pseu-domyocardial infarction pattern has been reported toappear as massive ST-T segment elevation developssecondary to derangements in myocyte repolariza-

tion.19-23

Early stages of hyperkalemia may manifestwith only shortening of the PR and QT interval.8

Sinus tachycardia and bradycardia, idioventricularrhythm, and 1st-, 2nd-, and 3rd-degree heart blockhave all been described on the presenting electrocar-diograms of patients with hyperkalemia.7 Given thevast array of electrocardiographic manifestations ofhyperkalemia, the difficulty in consistently identify-ing hyperkalemia on the basis of electrocardiographicabnormalities, and the fact that the electrocardiogramduring hyperkalemia may progress from normal tothat of ventricular tachycardia and asystole precipi-tously, physicians need to consider this diagnosis in

patients at risk.8

Causes of Hyperkalemia

Numerous causes of hyperkalemia are seen in clinicalpractice. The most common are renal disease and theingestion of medications that predispose the patientto hyperkalemia.2 Medications known to cause hyper-kalemia include angiotensin-converting enzyme in-hibitors, angiotensin-receptor blockers, penicillin G,trimethoprim, spironolactone, succinylcholine, alter-

maximum conductance of these channels occurs ap-proximately 50 msec after the initiation of phase 0and is reflected in phase 2 of the action potential.7

During phase 2, potassium efflux and calcium in-flux offset one another so that the electrical chargeacross the cell membrane remains the same, and theso-called plateau phase of the action potential is cre-ated (Fig. 3). During phase 3, the calcium channelsclose, while the potassium channels continue to con-duct potassium out of the cell; in this way, the elec-tronegative membrane potential is restored.7 One ofthe potassium currents (Ikr), located on the myocytecell membrane, is mostly responsible for the potas-sium efflux seen during phases 2 and 3 of the cardiacaction potential.10 For reasons that are not well under-stood, these Ikr currents are sensitive to extracellularpotassium levels, and as the potassium levels increasein the extracellular space, potassium conductancethrough these currents is increased so that more potas-sium leaves the myocyte in any given time period.10

This leads to an increase in the slope of phases 2 and 3of the action potential in patients with hyperkalemiaand therefore, to a shortening of the repolarizationtime. This is thought to be the mechanism responsiblefor some of the early electrocardiographic manifesta-tions of hyperkalemia, such as ST-T segment depres-sion, peaked T waves, and Q-T interval shortening.11,12

Surface Electrocardiogram

Manifestations of Hyperkalemia

In experimental models, there is a very orderly pro-gression of electrocardiographic changes induced byhyperkalemia.13,14 The earliest electrocardiographic

manifestation of hyperkalemia is the appearance ofnarrow-based, peaked T waves. These T waves are ofrelatively short duration, approximately 150 to 250msec, which helps distinguish them from the broad-based T waves typically seen in patients with myocar-dial infarction or intracerebral accidents.7 Peaked Twaves are usually seen at potassium concentrationsgreater than 5.5 mEq/L and are best seen in leads II,III, and V2 through V4, but are present in only 22% ofpatients with hyperkalemia.8,11,15 It may be that in-creased myocyte excitability, shortening of the myo-cyte action potential, and an increase in the slope ofphase 2 and 3 of the action potential account for the

T wave peaking seen in mild hyperkalemia.11As serum potassium levels increase to greater than

6.5 mEq/L, the rate of phase 0 of the action potentialdecreases, leading to a longer action potential and, inturn, a widened QRS complex and prolonged PR in-terval. Electrophysiologically, this appears as delayedintraventricular and atrioventricular conduction.7,11Asthe intraventricular conduction delay worsens, theQRS complex may take on the appearance of a left orright bundle branch block configuration. A clue that


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native medicines, and heparin, to name just a few.24-30

In their study in a university setting, Acker and col-leagues2 reported that 75% of all patients with severehyperkalemia had renal failure, and 67% were takinga drug that predisposed them to hyperkalemia. Otherless common causes of hyperkalemia include massivecrushing injury with resultant muscle damage, largeburns, high-volume blood transfusions, human im-munodeficiency virus infection, and tumor lysis syn-drome.8,31-35 In many patients, the cause of hyperka-lemia is multifactorial and never clearly defined.

Treatment of Hyperkalemia

Although hyperkalemia is one of the deadliest electro-lyte abnormalities, it is also one of the most treatable.As previously discussed, the diagnosis of hyperkalemiacan be difficult if one relies solely on electrocardio-graphic criteria. Frequently, physicians must initiatetreatment for hyperkalemia on the basis of a patientsclinical scenario (such as a cardiac arrest occurring in a

chronic dialysis patient). More commonly, however,the patient is treated when laboratory data becomeavailable. Most authorities recommend treatment forhyperkalemia when electrocardiographic changes arepresent or when serum potassium levels are greaterthan 6.5 mEq/L, regardless of the electrocardiogram.36,37

The treatment for hyperkalemia can be thought of in3 distinct steps. First, antagonize the effects of hyper-kalemia at the cellular level (membrane stabilization).Second, decrease serum potassium levels by promotingthe influx of potassium into cells throughout the body.Third, remove potassium from the body.

Membrane Stabilization. The initial treatment of

hyperkalemia should be the infusion of calcium. Cal-cium antagonizes the effects of hyperkalemia at thecellular level through 3 major mechanisms. First, inthe setting of hyperkalemia, the resting membrane po-tential is shifted to a less negative value, that is, from90 mV to 80 mV, which in turn moves the restingmembrane potential closer to the normal thresholdpotential of 75 mV, resulting in increased myocyteexcitability. When calcium is given, the threshold po-tential shifts to a less negative value (that is, from 75mV to 65 mV), so that the initial difference betweenthe resting and threshold potentials of 15 mV can berestored.38 For example, if a myocyte has a normal

resting membrane potential of 90 mV and a normalthreshold potential of 75 mV, then 15 mV of depo-larization is required before reaching the thresholdpotential. In the setting of hyperkalemia, the restingmembrane potential may change to a new level (thatis, 80 mV), so that now only 5 mV of depolarizationmust occur before reaching the threshold potential of75 mV. When calcium is given, the threshold poten-tial becomes less negative (that is, it changes from 75mV to 65 mV). Thus the difference between the hy-

perkalemia-induced resting membrane potential of80 mV and the calcium-induced threshold potentialof 65 is now back to 15 mV, and myocyte excitabili-ty can return to normal.

Second, it has been shown in animal studies that in-creasing levels of calcium shift the curve relating Vmax tothe resting membrane potential at the onset of actionpotential upward and to the right (Fig. 5).9 Therefore,at any given level of resting membrane potential, up toapproximately 75 mV, the Vmax is increased when highcalcium concentrations are present.39 This serves to re-turn myocyte excitability back to normal in the settingof hyperkalemia, where myocyte depolarization is de-creased secondary to decreased rates of Vmax.

Finally, in cells with calcium-dependent action po-tentials, such as SA and atrioventricular nodal cells,and in cells in which the sodium current is depressed,an increase in extracellular calcium concentration willincrease the magnitude of the calcium inward currentand the Vmax by increasing the electrochemical gra-

dient across the myocyte. This would be expected tospeed impulse propagation in such tissues, reversingthe myocyte depression seen with severe hyperkale-mia.40

The effects of intravenous calcium occur within 1 to3 minutes but last for only 30 to 60 minutes. There-fore, further, more definitive treatment is needed tolower serum potassium levels. Calcium gluconate is thepreferred preparation of intravenous calcium. Thedose should be 10 mL of a 10% calcium gluconatesolution infused over 2 to 3 minutes. Calcium chlo-ride may also be used but provides about 3 times theamount of calcium per 10-mL dose, so the dose needs

to be attenuated accordingly to avoid potential calci-um toxicity.36 Because hypercalcemia can potentiate


Fig. 5 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

mV, increasing calcium levels lead to an increase in Vmax.

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a quick or sustained decrement in potassium levels,physicians should reserve the use of intravenous sodi-um bicarbonate for situations wherein severe acidemiais present or there is another indication for its admin-istration (such as phenobarbital or tricyclic antide-pressant overdose).

Potassium Removal from the Body. The final task intreating patients with severe hyperkalemia is to re-move potassium from the patients body. The quick-est, most efficient way to do this is through the use ofhemodialysis.42 In 1970, Morgan and colleagues51 re-ported the removal of 48 mEq/L of potassium using aKiil dialyzer over a 10-hour period; others confirmedthese f indings.52,53 Because of the time, expense, andinvasive nature of hemodialysis therapy, it is rarelyused as a 1st-line treatment for hyperkalemia unless apatient is already on dialysis and has life-threateninghyperkalemia. For most patients, treatment with anexchange resin such as sodium polystyrene sulfonateis more appropriate.

Ion exchange resins can be administered orally orrectally and work by exchanging gut cations, most im-portantly potassium, for sodium ions that are releasedfrom the resin. Most studies have found exchangeresins to decrease serum potassium levels by about 1mEq/L over a 24-hour period.54 It should be empha-sized that the extended time required for exchangeresins to work exclude their use in the emergent treat-ment of hyperkalemia. Exchange resins can causesignificant constipation and are typically given in com-bination with a laxative such as sorbitol. Not only doesa laxative prevent constipation, but it also promotes theelimination of potassium from the gut once it binds to

the resin. Although generally safe, the combination of aresin and sorbitol has been reported to cause intestinalnecrosis, and as such should be used cautiously andonly when necessary.36,55,56

Conclusion

As our case presentation illustrates, hyperkalemia canbe very challenging to diagnose. Patients with severehyperkalemia frequently have normal electrocardio-grams or electrocardiographic abnormalities that aredifficult to attribute to hyperkalemia. The diagnosisof hyperkalemia must be considered in any patient

with clinical risk factors that would predispose themto its development. Most commonly, patients withhyperkalemia have underlying renal dysfunction orare taking a medication known to increase serum po-tassium concentrations. The treatment of hyperka-lemia must be swift and appropriate to prevent thedevelopment of fatal cardiac arrhythmias. If a patienthas electrocardiographic evidence of hyperkalemia, orthe potassium level is greater than 6.5 mEq/L, the 1stdrug to be administered should be calcium, because

digitalis toxicity, calcium should be used in patientstaking digitalis only if there is loss of P waves or awidened QRS complex.8 In this situation, calcium glu-conate should be diluted in 100 mL of D5W (dextrose[5%] in water) and infused over 30 minutes.

Promotion of Potassium Influx into Cells.After theadministration of calcium, the next goal of treatmentis to shift potassium intracellularly. This is most fre-quently done by giving insulin. Insulin stimulates theNa-K ATPase pump, which moves potassium intra-cellularly in exchange for sodium in a 2:3 ratio; this ef-fect is independent of insulins effect on glucose.41 Tenunits of intravenous insulin is typically given, followedby close monitoring of serum blood sugar. Fifty mL of50% dextrose is frequently co-administered with insu-lin in normoglycemic patients to prevent hypoglyce-mia. If a patient is already hyperglycemic, supplementalglucose is not needed. The effect of the insulin is seenwithin 10 to 20 minutes of administration and can beexpected to decrease potassium levels by 0.6 to 1.0

mEq/L.36,42,43

Growing evidence suggests that there may be a rolefor albuterol in the treatment of patients with severehyperkalemia. Catecholamines activate Na-K ATPasepumps through 2 receptor stimulation in a mannerthat is additive to the effect of insulin.36,44 In a studyby Montoliu and coworkers,41 0.5 mg of intravenousalbuterol was given to patients with hyperkalemia,leading to a 1-mEq/L decrease in serum potassiumlevels with minimal adverse effects.41 Because there areno approved intravenous forms of agonists availablein the United States, studies have been performed todetermine whether nebulized agonists would have a

similar effect on serum potassium levels. One suchstudy found that albuterol, when given in very highdoses (1020 mg vs the normal 0.5 mg), decreased po-tassium levels by 0.62 to 0.98 mEq/L.45 The onset ofaction for inhaled albuterol was immediate and lastedfor 1 to 2 hours. Although in these studies the effectsvaried among individuals, 2 agonist administrationwas found to be safe and was associated with a signifi-cant decrease in serum potassium levels. Therefore, 2agonist therapy should be considered as an adjunctivetreatment for patients with severe hyperkalemia.

Sodium bicarbonate infusion can shift potassiumfrom the extracellular to intracellular space by in-

creasing blood pH. However, routine bicarbonatetherapy for the treatment of hyperkalemia is contro-versial.36,46-49 In a study by Blumberg and associates,50

12 dialysis patients with potassium levels of 5.25 to8.15 mEq/L received 390 mmol of intravenous so-dium bicarbonate over a 6-hour period. No changein potassium levels was seen until 4 hours after drugadministration, when a decrease of 0.7 mEq/L wasnoted; at 6 hours, however, the decrease in potassi-um level was only 0.35 mEq/L.50 Due to the lack of


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of its rapid onset of action and ability to stabilizemyocyte electrical activity. Insulin, with or withoutglucose, and 2 agonists should then be quickly ad-ministered to decrease extracellular potassium levels.Exchange resins and hemodialysis are then used, inthe appropriate clinical settings, to decrease systemicpotassium levels. Sodium bicarbonate therapy has lit-tle use in the routine treatment of hyperkalemia un-less severe metabolic acidosis is present. Finally, and asa matter of course, physicians should perform a thor-ough search to identify the cause of the hyperkalemiain their patient in order to prevent a recurrence.

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