Digitalis, electrolytes and the surgical patient

Lown, Bernard; Black, Harrison; Moore, Francis D.

doi:10.1016/0002-9149(60)90320-9

Cited by 91 publications

(27 citation statements)

References 70 publications

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“…It is possible that under appropriate clinical conditions it may be advisable not to discontinue digitalis if the arrhythmia can be controlled with K. It must be appreciated, however, that the elevation of serum K necessary to suppress the toxic arrhythmias may be difficult to attain continuously. It must also be recognized that the administration of K may produce a more rapid and potentially dangerous elevation in the plasma level of this ion in the presence of digitalis than in its absence (39)(40)(41).…”

Section: Resultsmentioning

confidence: 99%

Studies on digitalis. 13. A comparison of the effects of potassium on the inotropic and arrhythmia-producing actions of ouabain.

Williams¹,

Klocke²,

Braunwald³

1966

J. Clin. Invest.

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Although it is generally recognized that digitalis-induced arrhythmias can be suppressed by the administration of potassium (1-3), it is not clear whether the potassium ion also influences the positive inotropic effect exerted by the glycosides on the intact mammalian heart. Clarification of this problem is important in the understanding of the interrelationships between the actions of glycosides and potassium, and is clinically significant in view of the frequency with which potassium is administered to patients who are or have been receiving digitalis. Accordingly, the present investigation was undertaken to determine the manner in which potassium suppression of ouabaininduced arrhythmias affects the augmentation of ventricular contractile force produced by the administration of the glycoside. MethodsTen mongrel dogs, weighing between 10 and 25 kg, were anesthetized with intravenous sodium pentobarbital (35 mg per kg) and ventilated with a positive displacement pump that was supplied with a mixture of room air and 100% 02. The right ventricle was exposed through a median sternotomy, a Walton-Brodie strain gauge arch (4) was sutured to the right ventricle, and the muscle segment beneath the gauge was stretched approximately 50% beyond its initial length. This maneuver allows recording of the changes in contractile force of the segment of myocardium between the points of attachment of the gauge despite some changes in right ventricular dimensions (5). Heparin, 5 mg per kg, was administered intravenously. With a compressed air-blood reservoir that was connected to a femoral artery through a large bore cannula, mean arterial pressure was maintained constant despite any changes in blood volume that might have occurred as a consequence of bleeding or blood withdrawal for plasma K concentration. Body tempera-* Submitted for publication June 9, 1965; accepted November 26, 1965. f Address requests for reprints to Dr. Eugene Braunwald, Cardiology Branch, National Heart Institute, Bethesda, Md. 20014. ture was monitored with a thermistor probe placed in the superior vena cava and was maintained constant with heating pads. Femoral arterial pressure was measured with a Statham P23D strain gauge transducer, and arterial blood was withdrawn at intervals for determinations of plasma K by flame photometry. Right ventricular contractile force, arterial pressure, and a limb lead of the electrocardiogram were recorded continuously on a direct-writing oscillograph. In two of the ten animals the sinoatrial node was crushed and heart rate maintained constant by stimulating the right atrium at a rate just above the spontaneous rate. Two animals had undergone bilateral adrenalectomy 1 week before the experiment and were then maintained on steroid replacement therapy.After control measurements, an intravenous dose of ouabain, 30 tzg per kg, was administered over a 5-minute period. Ten to 15 minutes later a constant infusion of ouabain, 30 jzg per kg per hour, was begun and was continued for the remainder of the experiment. Ouabai...

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Section: Resultsmentioning

confidence: 99%

Studies on digitalis. 13. A comparison of the effects of potassium on the inotropic and arrhythmia-producing actions of ouabain.

Williams¹,

Klocke²,

Braunwald³

1966

J. Clin. Invest.

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“…This knowledge permits greater understanding of the iatrogenic hypocalc2emia produced by transfusion with large amounts of citrated blood, a not uncommon occurrence in the surgical patient (Lown et al, 1960).…”

Section: Commentsmentioning

confidence: 99%

Myocardial Responses to Chelation

Soffer¹,

Toribara²,

Sayman³

1961

Heart

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The phenomena of displacement and immobilization of calcium ions by chelation is being studied in an increasing number of clinical states. Chelation therapy in hypercalcmmia (Holland et al., 1953;Spencer et al., 1956), calcium deposition in coronary arteries (Meltzer et al., 1960) and peripheral vessels (Clarke et al., 1960) and in skin (Muller et al., 1959), and in the treatment of digitalis toxicity (Cohen et al., 1959) are under scrutiny and therefore careful analysis of the myocardial action of chelating drugs is warranted. In a 28-month study, 125 intravenous infusions of disodium ethylenediaminetetraacetate (disodium edathamil or EDTA) were administered to 58 subjects. Chelation produced four characteristic though occasionally variable responses of ventricular, atrial, and atrio-ventricular (A-V) junctional tissue: (1) suppression of ectopic ventricular beats and ventricular tachycardia, (2) slight slowing of the sino-atrial pacemaker, (3) improvement of A-V nodal conduction in first degree, second degree, and advanced heart block, and (4) increased automaticity of idioventricular pacemakers in complete heart block. Since the slowest effective rate of administration is the safest rate (Spencer et al., 1952), the total quantity of calcium chelated was determined for periods of administration varying from one-half to eleven hours. METHODSThere were 58 subjects, 17 men and 41 women, with a mean age of 65 years. The arrhythmias present were ventricular premature contractions, 18 patients; atrial fibrillation, 11; complete heart block, 7; first-degree heart block, 6; ventricular tachycardia, 4; second degree heart block, 4; advanced heart block, 2; paroxysmal atrial tachycardia with block, 2; atrial flutter, 1; A-V dissociation with a nodal rate above 70, 2; nodal rhythm with ventricular premature contractions and A-V dissociation, 1. Thirty-two patients had a basic sino-atrial pacemaker and 17 were in a state of digitalis intoxication. The disodium EDTA was given in dosages of from 0 5 g. to 4 g. in periods ranging from one-half hour to 11 hours. In three instances 3 g. were administered in 30 minutes but in all other cases the rate of infusion never exceeded 4 g. in 60 minutes. The drug was diluted in either 500 c.c. or 1000 c.c. of 5 per cent glucose in water. The concentration of the drug was maintained below 0 5 per cent unless congestive failure prohibited the use of dilute solutions. Ultrafiltrable serum calciums were determined by the method of Toribara and Terepka (Toribara et al., 1957). Samples deproteinized with trichloracetic acid were used for determining total serum calcium. Ashing with concentrated nitric acid was necessary to obtain complete recovery of chelated calcium.

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“…24 Ample clinical and experimental evidence attests to the fact that myocardial sensitivity can strikingly change at any one drug level. 25 When arrhythmias arise in the digitalized patient with heart failure, the meaning of the serum digoxin concentration may be unclear, since blood levels do not in themselves define myocardial susceptibility to In order to determine the degree of digitalization and to assess myocardial sensitivity to the glycosides, Lown and Levine in 1953 proposed a biologic titration employing the ultra rapid acting digitalis agent, acetyl strophanthidin. 28 The present report describes a large clinical experience with acetyl strophanthidin in patients receiving maintenance digoxin therapy.…”

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confidence: 99%

Comparison of Serum Digoxin Level Measurement with Acetyl Strophanthidin Tolerance Testing

et al. 1974

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SUMMARYSerum digoxin levels (SDL) were compared with tolerance for the rapidly acting cardiac aglycone, acetyl strophanthidin (AS). AS titration tests were performed on 133 patients with diverse cardiac disorders. All were receiving maintenance digoxin. Both exquisite AS sensitivity and tolerance for a 1.0 mg AS were associated with a wide range of SDL values. Concordance and discordance between the two methods in assessing degree of digitalization were evaluated by considering SDL of 1.4 ng/ml to be the mean value for patients without glycoside-induced cardiac arrhythmia. An SDL of <1.5 ng/ml with tolerance for 1.0 mg AS and an SDL of >1.4 ng/ml with sensitivity to 1.0 mg AS or less constituted concordant responses. An SDL of <1.5 ng/ml with intolerance for 1.0 mg or less AS and an SDL of >1.4 ng/ml with tolerance for 1.0 mg AS comprised discordant responses. In 60 of 144 (42%) AS titrations discordant results were observed. Severe pulmonic, coronary, and aortic valvular heart disease, as well as old age, contributed to unusual AS sensitivitv. Titration with AS clarified pharmacologic quantification of SDL by providing insight into optimum therapeutic glycoside dose. Development of a radioimmunoassay for digoxin promised to resolve questions concerning appropriate dosage of this commonly employed digitalis glycoside. Several studies indicated that the quantity of drug present in the serum could be determined with precision. 9 Serum digoxin concentration measurements delineated a therapeutic range of values and provided a convenient marker for differentiating toxic from nontoxic patients with cardiac arrhythmias.20' 21 Eighty-five percent of patients with manifestations suggesting digitalis intoxication showed blood levels above 2.0 ng/ml; while a similar percentage of those without evidence of overdosage had concentrations below this value.22 However, the range of overlap between toxic and nontoxic groups was wide, from 1.6-3.0 ng/ml.22 More recent reports indicate an even wider range of overlap, extending through virtually the entire serum digoxin concentration span encountered clinically.23Implicit in the clinical use of serum digoxin levels for assessing the state of digitalization are two assumptions: first, that blood levels reflect faithfully myocardial drug concentrations, and second, that a given concentration is associated with specific effect.

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Digitalis, electrolytes and the surgical patient

Cited by 91 publications

References 70 publications

Studies on digitalis. 13. A comparison of the effects of potassium on the inotropic and arrhythmia-producing actions of ouabain.

Studies on digitalis. 13. A comparison of the effects of potassium on the inotropic and arrhythmia-producing actions of ouabain.

Myocardial Responses to Chelation

Comparison of Serum Digoxin Level Measurement with Acetyl Strophanthidin Tolerance Testing

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