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Parenteral Adrenergic Bronchodilators and Potassium

1986; Elsevier BV; Volume: 89; Issue: 3 Linguagem: Inglês

10.1378/chest.89.3.322

1931-3543

Markus Küng,

Ion channel regulation and function

The fact that therapy with intravenously-infused epinephrine lowers the serum potassium (K+) concentration in cats has been known for more than 50 years.1D'Silva JL The action of adrenaline on serum potassium.J Physiol. 1934; 82: 393-398Crossref PubMed Scopus (106) Google Scholar It is now well-established that the effect of catecholamines on K+ homeostasis is mediated through beta adrenoceptors, specifically, the beta2 type.2Brown MJ Brown DC Murphy MB Hypokalemia from beta2-receptor stimulation by circulating epinephrine.N Engl J Med. 1983; 309: 1414-1419Crossref PubMed Scopus (546) Google Scholar Activated beta2 receptors stimulate the Na+-K+ pump via the activation of adenyl cyclase.3Clausen T Flatman JA The effect of catecholamines on Na-K transport and membrane potential in rat soleus muscle.J Physiol. 1977; 270: 383-414Crossref PubMed Scopus (341) Google Scholar The net result is an enhanced active transport of K+ from the extracellular to the intracellular compartment, and of Na+ in the opposite direction. Cellular K+ influx is further facilitated by the ability of beta agonists to directly stimulate insulin secretion. Finally, a phenomenon well within the domain of the pulmonologist possibly contributes to the K+ shift: stimulation of ventilation by beta adrenergic agonists4Heistad DD Wheeler RC Mark AL Schmid PG Abboud FM Effects of adrenergic stimulation on ventilation in man.J Clin Invest. 1972; 51: 1469-1475Crossref PubMed Scopus (144) Google Scholar may lead to respiratory alkalosis and thus promote hypokalemia. The K+ shift induced by any of these mechanisms is transient and occurs at the expense of the extracellular space and, ultimately, to the detriment of the serum or plasma K+ concentration. In this issue of Chest, Rohr and co-workers (see page 348) report on the occurrence of hypokalemia after parenteral administration of albuterol and epinephrine. Because the dose of intravenous albuterol (250 μg) used by the authors was smaller than the subcutaneous or intramuscular dose (500 μg), direct quantitative comparisons of any measured parameter between the different modes of drug administration must take this difference into account. Nevertheless, the authors’ findings have at least one important practical implication: serum K+ levels obtained shortly after parenteral administration of albuterol or epinephrine should be interpreted with awareness of the K+-lowering effect of these drugs. Low or low-normal serum K+ levels measured under these conditions may reflect transient and self-correcting K+ redistribution, rather than absolute K+ deficiency. Except for its relevance in certain groups of heart patients, the clinical significance of hypokalemia remains a controversial issue.5Harrington JT Isner JM Kassirer JP Our national obsession with potassium.Am J Med. 1982; 73: 155-159Abstract Full Text PDF PubMed Scopus (122) Google Scholar, 6Knochel JP Diuretic-induced hypokalemia.Am J Med. 1984; 77: 18-27Abstract Full Text PDF PubMed Scopus (76) Google Scholar Whether the rapid change in the extracellular K+ concentration associated with the use of beta agonists contributes to the well-known tendency of these drugs to cause cardiac arrhythmias (and if so, to what extent) is not known. There is evidence that the effect of intravenously infused epinephrine on the serum K+ level is more pronounced in previously hypokalemic than in normokalemic volunteers.7Struthers AD Whitesmith R Reid JL Prior thiazide diuretic treatment increases adrenaline-induced hypokalaemia.Lancet. 1983; 1: 1358-1361Abstract PubMed Scopus (126) Google Scholar Consequently, should one attempt to replace K+ intravenously in hypokalemic patients before and while they are treated with parenteral beta agonists? Or is it not likely that, for most bronchospastic patients, the hazards of even a short delay in beginning effective bronchodilator therapy would be greater than the benefits of aggressive K+ replacement? The concern of Rohr and co-workers regarding the possible effect of sequential administration of beta agonists on K+ levels seems to be justified. For example, package inserts of injectable brands of terbutaline recommend the administration of a second dose in the absence of significant clinical improvement 15 to 30 minutes after the first dose. Yet, for this particular drug, this happens to be the time of maximal effect of the initial dose on serum K+ levels.8Küng M White JR Burki NK The effect of subcutaneously administered terbutaline on serum potassium in asymptomatic adult asthmatics.Am Rev Respir Dis. 1984; 129: 329-332Crossref PubMed Google Scholar Side effects and complications associated with the use of beta adrenergic agents have recently been reviewed.9Committee on drugs The American Academy of Allergy and Immunology Adverse effects and complications of treatment with beta-adrenergic agonist drugs.J Allergy Clin Immunol. 1985; 75: 443-449Abstract Full Text PDF PubMed Scopus (37) Google Scholar Legitimate concerns such as the risk of transient hypokalemia not withstanding, these bronchodilators have withstood the test of time. They were used extensively long before the effect on K+ homeostasis gained clinical attention. Since bronchodilatation and hypokalemia are mediated through the same type of receptors, one wonders whether any future adrenergic compound with systemic action could promise to deliver one without the other. For injectable brands of terbutaline, the 39th edition of the PDR (1985) lists transient hypokalemia under the heading, “Usage in Labor and Delivery.” Hypokalemia is not cited as an “adverse effect” in the sections on terbutaline or epinephrine. Using close cardiac monitoring, one should not worry too much, and let these bronchodilators do what they do best: dilate bronchi.