Concise Definitive Review R. Phillip Dellinger, MD, FCCM, Section Editor Management of severe hyperkalemia Lawrence S. Weisberg, MD Background and Objectives: Hyperkalemia is one of the few Results and Conclusions: A more complete understanding of potentially lethal electrolyte disturbances. Prompt recognition and potassium homeostasis in recent years has led to new ap- expeditious treatment of severe hyperkalemia are expected to proaches to the management of severe hyperkalemia. The phys- save lives. This review is intended to provide intensivists and iologically based sequential approach still applies. The efficacy, other interested clinicians with an understanding of the patho- pitfalls, and risks of the agents available for use at each step in physiology that underlies hyperkalemia, and a rational approach the sequence are critically reviewed. Rational use of the available to its management. tools will allow clinicians to successfully treat severe hyperkale- Methods: This article reviews and analyzes literature relevant mia. (Crit Care Med 2008; 36:3246–3251) to the pathophysiology and management of severe hyperkalemia. KEY WORDS: hyperkalemia; treatment; critical illness Methods include search of MEDLINE, and bibliographic search of current textbooks and journal articles. yperkalemia is common in rium is modulated by insulin (3–5), cat- panies acute kidney injury, particularly in hospitalized patients, and echolamines (6, 7) and, to a lesser extent, the setting of mineralocorticoid defi- may be associated with ad- by acid-base balance (8–10), plasma to- ciency (13–15). Such mineralocorticoid verse clinical outcomes (1, nicity, and several other factors (3). The deficiency is often induced by drugs that H2). Its prevalence and clinical impact in interfere with the renin-angiotensin- other system governs K homeostasis over critically ill patients are unknown. There the long-term by regulating external bal- aldosterone axis and commonly causes is no doubt, however, that severe hyper- ance: the parity between K intake and hyperkalemia in patients with chronic kalemia can be fatal. Proper treatment of elimination. In individuals with normal kidney disease, as well (16, 17). Sustained hyperkalemia depends on an understand- renal function, the kidneys are responsi- hyperkalemia is always attributable to in- ing of the underlying physiology. ble for elimination of about 95% of the adequate renal K elimination. A detailed The ratio of extracellular to intracel- daily K load with the remainder exiting discussion of the causes of hyperkalemia lular potassium (K) concentration largely through the gut. External K balance is in critically ill patients is beyond the determines the cell membrane resting maintained largely by modulating renal K scope of this article, but may be found in electrical potential that, in turn, regu- elimination. a recent review (18). lates the function of excitable tissues Almost all the K excreted by the kid- (cardiac and skeletal muscle, and nerve) ney comes from K secreted in the distal Clinical Manifestations of (1). Small absolute changes in the extra- nephron (connecting tubule and collect- Hyperkalemia cellular K concentration will have large ing duct) (11). Virtually all regulation of effects on that ratio, and consequently on Alterations in P have a variety of ad- K excretion takes place at this site in the K the function of excitable tissues. Thus, it verse clinical consequences, the expres- nephron, under the influence of two prin- is not surprising that the plasma K con- sion of which may be magnified in the ciple factors: the rate of flow and solute centration (P ) normally is maintained critically ill patient. The most serious of K (sodium and chloride) delivery through within very narrow limits. This tight reg- these manifestations are those involving that part of the nephron; and the effect of ulation is accomplished by two coopera- excitable tissues. tive systems. One system defends against aldosterone (11). K secretion is directly Cardiac Effects. Hyperkalemia depo- proportional to flow rate and sodium de- short-term changes in PK by regulating larizes the cell membrane, slows ventric- internal balance: the equilibrium of K livery through the lumen of the distal ular conduction, and decreases the dura- across the cell membrane. This equilib- nephron, and to circulating aldosterone tion of the action potential. These levels in the setting of an aldosterone- changes produce the classic electrocar- sensitive epithelium. This explains, in diographic (EKG) manifestations of hy- part, why the use of diuretic drugs that From the Division of Nephrology, Department of perkalemia including (in order of their Medicine, UMDNJ-Robert Wood Johnson Medical work proximal to the K secretory site usual appearance) peaked T waves, wid- School, Cooper University Hospital, Camden, NJ. (loop and thiazide diuretics) often is ac- ening of the QRS complex, loss of the P The author has not disclosed any potential con- companied by hypokalemia. K secretion wave, “sine wave” configuration, or ven- flicts of interest. is inversely proportional to the chloride For information regarding this article, E-mail: tricular fibrillation and asystole (19, 20). [email protected] concentration of the luminal fluid and is These EKG changes may be modified by a Copyright © 2008 by the Society of Critical Care stimulated, for example, by luminal deliv- multitude of factors such as extracellular Medicine and Lippincott Williams & Wilkins ery of sodium bicarbonate (12). Con- fluid pH, calcium concentration, sodium DOI: 10.1097/CCM.0b013e31818f222b versely, hyperkalemia commonly accom- concentration, and the rate of rise of PK 3246 Crit Care Med 2008 Vol. 36, No. 12 Table 1. Emergency treatment of hyperkalemia Agent Dose Onset Duration Complications Membrane stabilization Calcium gluconate (10%) 10 mL IV over 10 min Immediate 30–60 min Hypercalcemia Hypertonic (3%) sodium chloride 50 mL IV push Immediate Unknown Volume overload hypertonicity Redistribution Insulin (short acting) 10 units IV push, with 25–40 g dextrose 20 min 4–6 hrs hypoglycemia (50% solution) Albuterol 20 mg in 4 mL normal saline solution, 30 min 2 hrs Tachycardia inconsistent nebulized over 10 min response Elimination Loop diuretics Furosemide 40–80 mg IV 15 min 2–3 hrs Volume depletion Bumetanide 2–4 mg IV Sodium bicarbonate 150 mmol/L IV at variable rate Hours Duration of infusion Metabolic alkalosis volume overload Sodium polystyrene sulfonate 15–30 g in 15–30 mL (70% sorbitol orally) Ͼ2 hrs 4–6 hrs Variable efficacy intestinal (Kayexalate, Kionex) necrosis Hemodialysis Immediate 3 hrs Arrhythmias (?) IV, intravenously. (19). Hospitalized patients with hyperka- and, thus, prevent correction of a meta- as arbitrary. Nonetheless, since the treat- lemia are reported to have a higher mor- bolic acidosis (29). ment for acute hyperkalemia is safe if tality rate than those without hyperkale- applied properly and hyperkalemia is po- mia (21, 22), but the high prevalence of Treatment of Severe tentially and unpredictably lethal, it is coexistent renal insufficiency in this pop- Hyperkalemia prudent to maintain a low threshold for ulation is a significant confounding vari- instituting emergency therapy. Because able that prevents attribution of the in- In general, the initial treatment of se- most patients manifest hyperkalemic creased mortality to the hyperkalemia vere hyperkalemia is independent of the EKG changes at PK greater than 6.7 itself. cause of the disturbance, whereas the ra- mmol/L (20), hyperkalemia should be Ͼ EKG changes may not accompany tional therapy of chronic hyperkalemia treated emergently for 1) PK 6.5 changes in PK. The sensitivity of the elec- depends on an understanding of its mmol/L or 2) EKG manifestations of hy- trocardiogram to reveal changes of hy- pathogenesis. perkalemia regardless of the PK (30). perkalemia is quite low (23). It does in- In considering when hyperkalemia Therapy of acute or severe hyperkale- crease in proportion to the severity of the constitutes an emergency, several points mia is directed at preventing or amelio- hyperkalemia (23), but normal electro- should be kept in mind. First, the elec- rating its untoward electrophysiologic ef- cardiograms have been seen even with trophysiologic effects of hyperkalemia are fects on the myocardium. The goals of extreme hyperkalemia (24) and the first directly proportional to both the absolute therapy, in chronologic order, are as fol- lows (Table 1): cardiac manifestation of hyperkalemia PK and its rate of rise (19). Second, con- may be ventricular fibrillation (25). (The current metabolic disturbances may ame- explanation for a normal electrocardio- liorate (e.g., hypernatremia, hypercalce- 1. Antagonize the effect of K on excitable gram in the setting of extreme hyperka- mia, alkalemia) or exacerbate (e.g., cell membranes. lemia is not entirely clear, but may relate hyponatremia, hypocalcemia, acidemia) 2. Redistribute extracellular K into cells. ͓ ͓ to a slow rate of rise in the PK 20, 24 ). the electrophysiologic consequences of 3. Enhance elimination of K from the Given this insensitivity of the electrocar- hyperkalemia (20, 24). Third, although body. diogram, EKG changes should not be the EKG manifestations of hyperkalemia considered necessary for the emergency are generally progressive and propor- Membrane Antagonism treatment of severe hyperkalemia. tional to the PK, ventricular fibrillation Neuromuscular Effects. Hyperkalemia may be the first EKG disturbance of hy- Calcium. Calcium