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Digitalis Intoxication EDWARD K. CHUNG Postgrad Med J: first published as 10.1136/pgmj.48.557.163 on 1 March 1972. Downloaded from Postgraduate Medical Journal (March 1972) 48, 163-179. CURRENT SURVEY Digitalis intoxication EDWARD K. CHUNG M.D., F.A.C.P., F.A.C.C. Professor of Medicine, Director, Electrocardiographic Laboratory From Division of Cardiology, Department ofMedicine, West Virginia University School of Medicine, Morgantown, West Virginia 26505 U.S.A. Introduction and within the same patient from time to time. Use Cardiac glycoside has probably been the most of the standard dosage for digitalization without valuable drug available for our medical practice adjusting to the individual response is a common from the time digitalis was introduced by a British cause for digitalis toxicity. It is not uncommon to physician, William Withering in 1785.1 It is well reach digitalis intoxication without achieving the de- documented that cardiac glycoside is an essential sired therapeutic effect especially in patients with in the of heart intractable congestive heart failure. In retrospect, drug management congestive failure by copyright. regardless of underlying heart disease and various otherwise inadequately explained death in patients supraventicular tachyarrhythmias, particularly atrial with refractory congestive heart failure can often be fibrillation with rapid ventricular response.2 attributed to digitalis intoxication. It should be It is unfortunate that there has been increasing pointed out that digitalis toxicity does not produce incidence of digitalis toxicity in recent years because pathognomonic change in the heart at necropsy. of the frequent usage of potent purified cardiac Although digitalis is certainly one of the oldest glycosides in conjunction with the potent diuretics drugs and the most commonly used drugs, it is not which predispose to the development of hypo- possible for physicians to determine precisely the kalaemia. The incidence of digitalis intoxication in optimal therapeutic dosage of the drug.2 The deter- general hospitals has been estimated to be approxi- mination of serum digoxin or digitoxin value is http://pmj.bmj.com/ mately 20%.2 3 Digitalis intoxication is often un- widely utilized at many institutions in the United avoidable becausethemargin between therapeutic and States of America as well as many European coun- toxic doses is relatively narrow. This narrow margin tries in order to assess the therapeutic and toxic becomes further reduced in elderly and seriously ill doses of digitalis. However, its clinical implication is patients with various modifying factors such as still not ideal because ofa significant overlap between hypokalaemia, myxoedema, hypoxia, pulmonary the therapeutic and toxic doses. Nevertheless, disease etc. It has been shown that the therapeutic markedly increased serum digitalis level certainly dose is approximately 60% of the toxic dose.2' 4 indicates digitalis toxicity whereas a very low level on September 24, 2021 by guest. Protected Although cardiac glycoside is an indispensable usually indicates under-digitalization.8-9 Serum digi- drug in the treatment of heart failure and various talis determination is extremely valuable when deal- supraventricular tachyarrhythmias, the drug is no ing with patients who suffer from intractable con- longer beneficial to the patient who develops toxic gestive heart failure and/or complex cardiac manifestations of digitalis.2 The toxic manifestations arrhythmias when little or no information regarding are an essential feature ofoverdosage with the cardiac previous digitalization is available. Details of serum glycosides. It is common experience that digitalis digitalis level determination will be discussed later intoxication may develop with a relatively small in this paper. dose, which is either therapeutic or inadequate for The most common manifestations of digitalis other patients. This is especially true when there intoxication are gastrointestinal disturbances, various are various modifying factors; such as electrolyte cardiac arrhythmias, aggravation of pre-existing imbalance, advanced age, myxoedema and advance- congestive heart failure or the development of new ment of underlying heart disease.5 Consequently, congestive heart failure, neurological disturbances digitalis requirement varies from patient to patient and visual disturbances.2 Common, uncommon and Postgrad Med J: first published as 10.1136/pgmj.48.557.163 on 1 March 1972. Downloaded from 164 Edward K. Chung TABLE 1. Manifestations of digitalis intoxication (Reproduced from Edward K. Chung, Digitalis Intoxication, Excerpta Medica, Amsterdam, 1969) Symptoms Frequency Various manifestations G-I symptoms Common Anorexia, nausea, vomiting Uncommon Diarrhoea, abdominal pain, constipation Cardiac Alteration of cardiac Development of CHF or aggravation of pre- manifestations contractile forces existing CHF Cardiac arrhythmias Atrial, A-V nodal, and ventricular arrhythmias and A-V block Neurologic Common Headache, fatigue, insomnia, malaise, confusion, disturbances depression, vertigo Uncommon Neuralgias (especially trigeminal), convulsions, paresthesiae, delirium, psychosis Visual Common Colour vision (usually green or yellow) with coloured halos Uncommon Blurring, shimmering vision Rare Scotomata, micropsia, macropsia, amblyopias (temporary or permanent) Rare Rare Allergic manifestations (urticaria, eosinophilia), manifestations idiosyncrasy, thrombocytopenia, gastro- intestinal haemorrhage and necrosis G-I, Gastro-intestinal; CHF, congestive heart failure. rare manifestations of digitalis intoxication are Diarrhoea is a rather uncommon manifestation of summarized in Table 1. digitalis toxicity and constipation or abdominal pain has been reported.2 Gastro-intestinal symptoms Gastro-intestinal symptoms are often not clearly evident in elderly patients, being by copyright. Anorexia is often the earliest sign of digitalis probably masked by the severity of the congestive toxicity and it is usually followed by nausea and heart failure and cerebral insufficiency. It is well vomiting within 2 to 3 days if digitalization is con- documented that most of the purified glycosides tinued.2 Nausea and vomiting are considered to be produce nausea and vomiting much less frequently central rather than gastric in origin, although direct than digitalis leaf. Thus, digitalis-induced arrhyth- gastric irritation may be partially responsible, par- mias are frequently the earliest manifestation of ticularly when a large initial dose of digitalis leaf is digitalis toxicity from these preparations.11-'4 When given. It is still uncertain whether digitalis-induced nausea and vomiting develop, and the possibilities vomiting results from a direct stimulation of a of over- or under-digitalization are almost equal, http://pmj.bmj.com/ vomiting centre in the medulla or reflexly from the digitalis should be discontinued immediately and heart. The central origin of vomiting is supported these patients should be re-evaluated. clearly by the fact that vomiting can be induced even after intravenous or intramuscular injections of Visual and neurological manifestations2' 15 17 digitalis.10 However, it is, at times, difficult to evdlu- Green or yellow colour vision with coloured halos ate the occurrence ofnausea and vomiting since these has been considered to be a pathognomonic feature manifestations may be due to underlying heart failure of digitalis toxicity for many years. Other visual on September 24, 2021 by guest. Protected itself and/or digitalis toxicity. In general, digitalis disturbances may include scotoma, blurring, shim- intoxication should be suspected when these gastro- mering vision, and less commonly, micropsia, intestinal symptoms reappear after a certain period macropsia, and temporary or permanent amblyo- of improvement. Digitalis toxicity is, needless to say, pias. These visual manifestations may easily be certain when other manifestations such as visual unrecognized unless the physician inquires speci- disturbances or cardiac arrhythmias co-exist. In fically for them. addition, digitalis toxicity should also be strongly Cardiac glycosides may produce various neuro- suspected when gastro-intestinal symptoms appear logical symptoms including headache, fatigue, lassi- associated with a worsening of heart failure after a tude, insomnia, malaise, depression, confusion, period of improvement. On rare occasions, certain delirium, and vertigo, and less commonly convul- patients may develop nausea and vomiting resulting sions, neuralgias, especially trigeminal nerve, and from hypersensitivity to a small amount of a paresthesiae, when toxicity develops. A tendency to particular preparation of glycoside. In this circum- psychosis in elderly individuals has been observed stance, another preparation of cardiac glycoside and in this case, the term 'digitalis delirium' has may be tried. been used. Visual and neurological manifestations Postgrad Med J: first published as 10.1136/pgmj.48.557.163 on 1 March 1972. Downloaded from Digitalis intoxication 165 usually develop later than gastro-intestinal symptoms ever, in many instances, it is not absolutely certain or cardiac arrhythmias and most of the above- whether aggravation ofcongestive heart failure is due mentioned symptoms are less specific for digitalis to some direct effect on the myocardium, electrolyte toxicity than gastro-intestinal manifestations or imbalance, digitalis-induced arrhythmias, or a com- arrhythmias, except for the colour vision. Further- bination of these. Regardless
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