Conclusion
The prolific author and physician Richard Gordon once cracked that “the history of medicine is largely the substitution of ignorance by fallacies” [42]. The conflation of fallacy and ignorance in the case of digitalis plus calcium may be the acceptance of Bower’s shaky case reports at the expense of Lieberman’s stronger—and arguably more useful—finding that the most important determinant of calcium toxicity is the dose and rate of infusion,whether or not digitalis glycosides are present. While some of the timidity surrounding digitalis treatment is grounded in rational evidence, much of it still seems to reflect subjective interpretation insulated from empirical reality. As Blaustein notes, the ancient toxic taboos associated with cardiac glycosides “scared off many physicians and nearly relegated digitalis to oblivion before it was perspica-ciously resurrected by [William] Withering” [12]. Like the “pseudoaxioms” [43] that epinephrine should never be injected into toes or that opioids will mask the abdominal exam findings in a surgical patient, the old digitalis-calcium “stone heart” taboo withers under a careful review of the evidence.
Article PDF
Similar content being viewed by others
Avoid common mistakes on your manuscript.
References
Hondehem LM and Roden DM. Agents used in cardiac arrhythmias. In: Katzung BG, editor. Basic & Clinical Pharmacology. 6th ed. Stamford, CT: Appleton & Lange; 1995.
Parham WA Mehdirad AA, Biermann KM, Fredman CS. Hyperkalemia revisited.Tex Heart Inst J 2006;33:40–47.
Acker CG, Johnson JP, Palevsky PM, Greenberg A. Hyperkalemia in hospitalized patients: causes, adequacy of treatment, and results of an attempt to improve physician compliance with published therapy guidelines.Arch Intern Med 1998;158:917–924.
Wrenn KD, Slovis CM, Slovis BS. The ability of physicians to predict hyperkalemia from the ECG.Ann Emerg Med 1991; 20:1229–1232.
Olson KR. Selected drugs and toxins and other causes of altered serum potassium. In: Olson KR et al., editors. Poisoning & Drug Overdose. 5th ed. New York: McGraw-Hill,2007. Table I-27, page 37.
Hollander-Rodriguez JC, Calvert JF. Hyperkalemia.Am Fam Physician 2006;73:283–290.
Perazella MA, Mahnensmith RL. Hyperkalemia in the elderly: drugs exacerbate impaired potassium homeostasis.J Gen Intern Med 1997;12(10):646–656.
Evans KJ, Greenberg A. Hyperkalemia: a review.J Intens Care Med 2005;20(5):272–290.
Hille B. Ionic Channels in Excitable Membranes. 2nd ed. Sunderland, MA: Sinauer, 1992, pp 460–461.
Guyton AC, Hall JE. Textbook of Medical Physiology. 9th ed. Philadelphia: WB Saunders,1996, pp 375–380.
Beeler GW Jr, Reuter H. Membrane calcium current in ventricular myocardial fibers.J Physiol 1970;207:191–209.
Blaustein MP. Physiological effects of endogenous ouabain: control of intracellular Ca2+ stores and cell responsiveness.Am J Physiol: Cell Physiol 1993;264(33): C1367-C1387.
Eichhorn EJ, Gheorghiade M. Digoxin—new perspective on an old drug.New Eng J Med 2002;347(18):1394–1395.
Alboni P, Shantha N, Filippi L, Pirani R, Preziosi S, Tomasi AM, Masoni A. Clinical effects of digoxin on sinus node and atrioventricular node function after pharmacologic autonomic blockade.Am Heart J 1984 Nov;108(5):1255–1261.
Reiffel JA, Bigger JT, Cramer M. Effects of digoxin on sinus nodal function before and after vagal blockade in patients with sinus nodal dysfunction: a clue to the mechanisms of the action of digitalis on the sinus node.Am J Cardiol 1979; 43:983–989.
Gomes JA, Kang PS, El-Sherif N. Effects of digitalis on the human sick sinus node after pharmacologic autonomic blockade.Am J Cardiol 1981;48:783–788.
Prindle, KH Jr, Skelton CA, Epstein SE, Marcus FI. Influence of extracellular potassium concentration on myocardial uptake and inotropic effect of tritiated digoxin.Circ Res 1971;28(3):337–345.
Goldman RH, Coltart DJ, Schweizer E, Snidow G, Harrison DC: The inotropic effects of digoxin in hyperkalemia: relation to (Na+-K+)-ATPase inhibition in the intact animal.Circulation 1973;48:830–838.
Meldgaard, LE, Steiness E, Waldorff S. Time course of ouabain uptake in isolated myocardial cells: dependence on extracellular potassium and calcium concentration.Br J Pharmacol 1981;73(2):341–345.
Macdonald JE, Struthers AD. What is the optimal serum potassium level in cardiovascular patients?J Am Coll Cardiol 2004;43(2):155–161.
Page E, Real JE. Interrelationships between cardiac effects of ouabain, hypocalcemia, and hyperkalemia.Circ Res 1955; 3:501–505.
Crippa G, Sverzellati E, Gieorgi-Pierfraceschi M, Carrara GC. Magnesium and cardiovascular drugs: interactions and therapeutic role.Ann Ital Med Int 1999;14(1):40–45.
Young IS, Goh EM, McKillop UH, Stanford CF, Nicholls DP, Trimble ER. Magnesium status and digoxin toxicity.Br J Clin Pharmacol 1991;32(6):717–721.
Marchlinski FE, Hook BG, Callans DJ. Which cardiac disturbances should be treated with digoxin immune Fab (ovine) antibody?Am J Emerg Med 1991 Mar;9(2 Suppl 1):24–28.
Ma G, Brady WJ, Pollack M, Chan TC. Electrocardiographic manifestations: digitalis toxicity.J Emerg Med 2001;20:145–152.
Kontani M, Hara A, Ohta S, Ikeda T. Hypermagnesemia induced by massive cathartic ingestion in an elderly woman without pre-existing renal dysfunction.Intern Med 2005 May;44(5):448–452.
Lewin NA. Cardiac glycosides. In: Goldfrank LR, Flomenbaum NI, Lewin NA, Weisman RS, Howland MA, Hoffman RS, editors.Goldfrank’s Toxicologic Emergencies. 6th ed. Stamford, CT: Appleton & Lange,1998, p. 798.
Bower JO, Mengle HAK. The additive effect of calcium and digitalis.JAMA 1936;106(14):1151–1153.
Ahmed J, Weisberg LS. Hyperkalemia in dialysis patients.Sem Dialysis 2001;14(5):348–356.
Lieberman AL. Studies on calcium: VI. Some Inter-relationships of the cardiac activities of calcium gluconate and scillaren-B.J Pharmacol Exp Ther 1933;47:183–192.
Rogen AS: Toxic manifestations of calcium therapy in heart failure.Lancet 1940;240(6216):452–453.
Gold H, Edwards DJ. The effects of ouabain on the heart in the presence of hypercalcemia.Am Heart J 1927;3:45–50.
Smith PK, Winkler AW, Hoff HE. Calcium and digitalis synergism: the toxicity of calcium salts injected into digitalized animals.Arch Intern Med 1939;64:322–329.
Lown B, Black H, Moore FD. Digitalis, electrolytes, and the surgical patient.Am J Cardiol 1960;6:309–337.
Nola GT, Pope S, Harrison DC. Assessment of the synergistic relationship between serum calcium and digitalis.Am Heart J 1970;79(4):499–507.
Ghaemmaghami CA, Harchelroad F. Dangers of intra-venous calcium chloride in the treatment of digoxin-induced hyperkalemia—fact or fiction? (Abstract)Acad Emerg Med 1999;6(5):378.
Hack JB, Woody JH, Lewis DE, Brewer K, Meggs WJ. The effect of calcium chloride in treating hyperkalemia due to acute digoxin toxicity in a porcine model.Clin Toxicol 2004;40(4):337–342.
Fenton F, Smally AJ, Laut J. Hyperkalemia and digoxin toxicity in a patient with kidney failure. Ann Emerg Med1996;28(4):440–441.
Van Deusen SK, Birkhahn RH, Gaeta TJ. Treatment of hyperkalemia in a patient with unrecognized digitalis toxicity.Clin Toxicol 2003;41:373–376.
Kuhn M. Digoxin, hyperkalemia and renal failure (Letter).Ann Emerg Med 1997;29(5):695–696.
Hoffman RS. What to do with case reports: is folly that succeeds folly nonetheless? (Editorial)J Toxicol Clin Toxicol 2003;41(4):377–379.
Gordon R. The Alarming History of Medicine: Amusing Anecdotes from Hippocrates to Heart Transplants. New York: St. Martin’s Griffin Press,1993.
Newman DH: Truth, and epinephrine, at our fingertips: unveiling the pseudoaxiom.Ann Emerg Med 2007;50:476–477.
Author information
Authors and Affiliations
Corresponding author
Additional information
There was no outside funding of any kind used for this study.
Rights and permissions
About this article
Cite this article
Erickson, C.P., Olson, K.R. Case files of the medical toxicology fellowship of the California poison control system—San Francisco: Calcium plus digoxin—More taboo than toxic?. J. Med. Toxicol. 4, 33–39 (2008). https://doi.org/10.1007/BF03160949
Issue Date:
DOI: https://doi.org/10.1007/BF03160949