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Chapter 14

Battle Casualties in Korea: Studies of the Surgical Research Team, Volume IV

The Electrocardiographic Effects of Alterations in Concentration of Plasma Chemicals*

    First Lieutenant Richardson F. Herndon, MC, USAR
    Major William H. Meroney, MC, USA
    Captain Carl M. Pearson, MC, USAR

The naturally occurring alterations in concentration of plasma chemicals which are known to produce configurational electrocardiographic changes are hypocalcemia,1-3 hyperkalemia1-41 and hypokalemia.2, 3, 12 Experimental evidence suggests that extracellular, not intracellular concentration is the factor producing electrocardiographic abnormality.13, 15, 16 Other electrolytes which may have an electrocardiographic effect are hydrogen ion, sodium, and bicarbonate, but it is not clear whether they have a direct effect upon cell polarization, or whether they influence chemicals which have a direct effect, or whether they are merely associated with changes in concentration of substances with direct effect.1-3, 12

Simultaneous changes in several electrolytes may interact to influence cardiac function. An isolated change in concentration of a single electrolyte cannot occur, because chemical equilibrium must be maintained, and various combinations of excess and deficiency of electrolyte concentration have been observed. Potassium excess, for instance, has been shown to exert exaggerated toxicity in the presence of calcium deficit, and replacement of the calcium deficit instantly modifies the cardiotoxic effects of the hyperkalemia.6, 7, 9-11, 17, 18 The present study is designed to reveal or define further the influence of certain plasma chemicals upon the electrocardiogram.

Materials and Methods

This is a study of 663 electrocardiograms recorded on 61 patients; at the same time venous blood was drawn for chemical analyses. The patients were combat casualties with acute renal insufficiency. The examinations were performed at the Renal Insufficiency Center, Korea, as an activity of the Surgical Research Team, Army Medical Service Graduate School, Washington, D. C. The electrocardiograms were 


*In press: American Heart Journal (Aug. 1955).


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made at the bedside with the Sanborn Visocardiette. Chemical determinations were performed by the following methods: nonprotein nitrogen by the method of Folin and Wu;19 chloride by the method of Sendroy;20 carbon dioxide content by the manometric method of Van Slyke;21 calcium* by the Clark and Collip modification of the method of Kramer and Tisdall;22 inorganic phosphorus by the method of Fiske and Subbarow;23 and sodium and potassium by the internal standard flame photometer.24

In the data and discussion to follow, QRS duration is measured in seconds, the QT interval (QTc) in seconds corrected for rate, where normal is 0.39±0.02 second,25 and T-wave height in millimeters from the isoelectric line of the tallest precordial T-wave.

Results

Part One: The QTc interval

A. Total plasma calcium is plotted against QTc interval in Figure 1. There is a tendency for the longer intervals to be associated with lower calcium values; that the relationship is not absolute and would stand little statistical tension is evident. The plasmas yielding these calcium values showed considerable variation in their potassium concentration, and the mutual antagonism between these ions may have affected the electrocardiographic response to variations in the calcium level. In Figure 2 the effect of variations of the concentration of plasma calcium is more clearly seen in four individual patients. An association between hypocalcemia and prolongation of the QTc interval has frequently been observed,1, 4, 8, 14 and if ionized calcium had been measured this relationship might have been more apparent in the composite chart. The high plasma calcium values were produced therapeutically with intravenous infusions of 10 per cent calcium gluconate in distilled water.

B. Inorganic phosphorus is plotted against QTc interval in Figure 3. A determination was not used if the patient had received calcium in the previous 24 hours. Again a rough correlation is observed. The relationship is due not to an effect of phosphorus elevation, but to the hypocalcemia with which it is associated in acute renal insufficiency.4, 17, f8 Figure 3 is, thus, a rough mirror image of Figure 1.

C. No consistent relationship was found between the QTc interval and the plasma levels of sodium, potassium, chloride, bicarbonate or nonprotein nitrogen.


*Ionized calcium was not measured.


287

FIGURE 1.

FIGURE 2.


288

FIGURE 3.

FIGURE 4.


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Part Two: The QRS complex.

A. Plasma potassium is plotted against QRS duration in Figure 4. Figure 5 is a plot of the same relationship in four individuals. Figure 6 is a plot of the relationship in patients who had not received calcium within 24 hours prior to the determinations. All charts show QRS duration to be normal until plasma potassium reaches 7.0 mEq./L. As potassium levels exceed 7.0 mEq./L. the QRS duration is usually prolonged. This is not constant since the QRS duration is at times normal even in the presence of a very high potassium level.

B. Potassium concentration was the only factor showing any consistent pattern when plotted against QRS duration. No such relationship was found between QRS duration and calcium, sodium, chloride, bicarbonate, phosphorus or nonprotein nitrogen plasma levels.

Part Three: The T-wave.

A. Figure 7 shows the relation of potassium to the height of the T-wave. Figure 8 shows the same in four patients. T-wave abnormality was rarely seen at potassium levels of less than 6.5 mEq./L., but became marked as hyperkalemia progressed. A comparison of patients in Figure 8 shows wide patient-to-patient variation.

B. A plot of T-wave height against the plasma concentration of either calcium, sodium, chloride, bicarbonate, phosphorus or nonprotein nitrogen did not show a consistent pattern.

Part Four: The composite electrocardiographic effects of progressive hyperkalemia.

There is a step-wise evolution of electrocardiographic abnormality in progressive hyperkalemia when calcium concentration is normal. This is shown in Figures 9 and 10. At plasma levels of less than 6.5 mEq./L. there is no effect on the electrocardiogram. The earliest electrocardiographic change is elevation and peaking of the T-waves, especially in the precordial leads, first seen at a plasma potassium level of about 6.5 mEq./L. As plasma potassium rises, this becomes more marked until the T-waves are very high, narrow and peaked.

The next change is a widening of the "S-ST" angle. The terminal portion of the QRS complex becomes wider and deeper. The initial portion of the QRS complex is unchanged. Overlapping this is a gradual loss of the ST segment. The end point of this effect is the most advanced hyperkalemic alteration. ST segment loss begins with a slight angulation of the ST segment from the iso-electric line. Angulation becomes more severe until the ST segment completely disappears.

As hyperkalemia progresses, a late electrocardiographic abnormality is gradual QRS broadening. This begins with S-ST angle widen-


290

FIGURE 5.

FIGURE 6.


291

FIGURE 7.

FIGURE 8.


292

FIGURE 9.

ing and is a prolongation only to the upper limits of normal. This increase appears to be largely a delay in the activation of the base of the right ventricle and is reminiscent of what is traditionally known as "right bundle-branch block." Later the initial vector of the QRS complex is also prolonged and the QRS resembles a rather indeterminate ventricular conduction defect. Here there may be rhythm disturbances, especially nodal rhythm. The PR interval may become prolonged, so much so that the P-wave is lost in the preceding T-wave.

Lastly, the lethal result of uninterrupted progressive hyperkalemia is the "sine" wave of ventricular fibrillation.


293

FIGURE 10.

Comment

These data show wide variation in the relationships between the concentration of plasma chemicals and the pattern of the simultaneously recorded electrocardiograms. We believe the explanation for this lies in the multiplicity of chemical abnormalities measured (and we did not measure them all), rather than in the factors embodied in the term "individual variation."

The electrocardiogram is an accurate, sensitive instrument for measurement of depolarization and repolarization of myocardial muscle cells. It is affected by various plasma electrolytes. The vari-


294

ation in concentration of a single electrolyte may be reflected with considerable precision by the electrocardiogram. However, it is impossible to vary a single electrolyte even experimentally for chemical equilibrium must be maintained.

Clinical situations are even more complicated. We have shown that if calcium concentration is normal, the electrocardiogram reflects the potassium level with considerable accuracy. The electrocardiographic changes produced by progressive increments of plasma potassium are rather predictable and consistent provided the additive effects of hypocalcemia are not superimposed. In our cases other concomitant changes in electrolyte concentration have not shown an appreciable effect. Our inability to show a consistent electrocardiographic reflection of alternations in concentration of plasma sodium has been especially disappointing.

The electrocardiogram does not lend itself well to the comparison of duration and amplitude measurements in different patients. Positional variations are difficult to eliminate; QRS duration and QT interval vary in normal persons. In addition, there are variations from the normal in our patients that defy measurement, such as the peaking of T-waves in hyperkalemia.

Often a changing pattern in serial tracings has been of more significance than a single tracing. We have observed several episodes of severe potassium intoxication interrupted by artificial dialysis in the same patient. Electrocardiograms serially taken in separate episodes recorded similar patterns at similar levels of hyperkalemia when other abnormalities had been corrected.26 Others have made like observations, finding the electrocardiogram to be an index of the level of hyperkalemia,8, 14 and that the electrocardiogram shows definite evidence of hyperkalemia when serum potassium exceeds 7.4 mEq./L.13 Other observers1, 8, 14 have found QT duration to be prolonged in hyperkalemia. We have been unable to do so. Hypocalcemia associated with hyperphosphatemia may account for the discrepancy.

Summary and Conclusions

1. Data from 663 electrocardiograms and blood chemical determinations in 61 patients are presented.

2. The relationships between the configuration of the electrocardiogram and the plasma concentration of potassium, calcium, sodium, phosphorus, chloride, bicarbonate and nonprotein nitrogen are discussed. Only potassium and calcium are demonstrated to have potent effect on the electrocardiogram in our series.


295

3. QTc interval is prolonged in hypocalcemia, and hyperphosphatemia. QRS duration is prolonged in hyperkalemia. T-wave amplitude is increased in hyperkalemia.

4. These data show wide variation in the electrocardiographic reflection of multiple electrolyte abnormalities. However, there is a step-wise evolution of electrocardiographic abnormality in progressive hyperkalemia when calcium concentration is normal.

References

1. White, P. D., and Mudd, S. G.: Observations on the Effect of Various Factors on the Duration of Electrical Systole of the Heart as Indicated by the Length of the QT Interval of the Electrocardiogram. J. Clin. Investigation 7: 387, 1929.

2. Katz, L. N.: Electrocardiography. Lea and Febiger, Philadelphia, 1946.

3. Spealman, C. R.: Action of Ions on the Mammalian Heart. Am. J. Physiol. 136: 332, 1942.

4. Merrill, J. P., Levine, H. D., Sommerville, W., and Smith, S., III: Clinical Recognition and Treatment of Acute Potassium Intoxication. Ann. Int. Med. 33: 797, 1950.

5. Levine, H. D., and Merrill, J. P.: Advanced Disturbances of the Cardiac Mechanism in Potassium Intoxication. Circulation 3: 889, 1951.

6. Winkler, A. W., Hoff, H. E., and Smith, P. K.: Factors Affecting the Toxicity of Potassium. Am. J. Physiol. 127: 430, 1939.

7. Govan, C. D., Jr., and Weiseth, W. M.: Potassium Intoxication: Report of an Infant Surviving a Serum Potassium Level of 12.27 Millimoles per Liter. J. Pediat. 28: 550, 1946.

8. Keith, N. M., Burchell, H. B., and Baggenstoss, A. H.: Electrocardiographic Changes in Uremia Associated with a High Concentration of Serum Potassium. Am. Heart J. 28: 817, 1944.

9. Marchand, J. F., and Finch, C. A.: Fatal Spontaneous Potassium Intoxication in Uremia. Arch. Int. Med. 73: 384, 1944.

10. Finch, C. A., Sawyer, C. G., and Flynn, J. M.: The Clinical Syndrome of Potassium Intoxication. Am. J. Med. 1: 337, 1946.

11. Winkler, A. W., Hoff, H. E., and Smith, P. K.: Electrocardiographic Changes and Concentration of Potassium in Serum Following Intravenous Injection of Potassium Chloride. Am. J. Physiol. 124: 478, 1938.

12. Darrow, D. C.: Body Fluid Physiology: The Role of Potassium in Clinical Disturbances of Body Water and Electrolytes. New Eng. J. Med. 242: 978, 1950; 242: 1014, 1950.

13. Elkinton, J. R., Tarail, R., and Peters, J. P.: Transfers of Potassium in Renal Insufficiency. J. Clin. Investigation. 28: 378, 1949.

14. Keith, N. W., and Burchell, H. B.: Clinical Intoxication with Potassium: Its Role in Severe Renal Insufficiency. Am. J. Med. Sc. 217: 1, 1949.

15. Crismon, J. M., Crismon, C. S., Calabresi, M., and Darrow, D. C.: Electrolyte Redistribution in Cat Heart and Skeletal Muscle in Potassium Poisoning. Am. J. Physiol. 139: 667, 1943.

16. Elkinton, J. R., Winkler, A. W., and Danowski, J. S.: The Importance of Volume and of Toxicity of Body Fluids in Salt Depletion Shock. J. Clin. Investigation 26: 1002, 1947.


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17. Meroney, W. H., and Herndon, R. F.: The Management of Acute Renal Insufficiency. J. A. M. A. 155: 877, 1954.

18. Meroney, W. H., and Herndon, R. F.: The Treatment of Potassium Intoxication with Calcium. (To be published.)

19. Folin, O. K. O., and Wu, H.: A System of Blood Analysis. J. Biol. Chem. 38: 81, 1919.

20. Sendroy, J., Jr.: A Note on the Photoelectric Microdetermination of Chloride in Biological Fluids. J. Biol. Chem. 142: 171, 1942.

21. Peters, J. P., and Van Slyke, D. D.: Quantitative Clinical Chemistry, Vol. 2. Williams and Wilkins, Baltimore, 1932.

22. Clark, E. P., and Collip, J. B.: A Study of the Tisdall Method for the Determination of Blood Serum Calcium with a Suggested Modification. J. Biol. Chem. 63: 461, 1925.

23. Fiske, C. H., and Subbarow, Y.: The Colorimetric Determination of Phosphorus. J. Biol. Chem. 66: 375, 1925.

24. Wallace, W. M., Holliday, M., Cushman, M., and Elkinton, J. R.: Application of Internal Standard Flame Photometer to Analysis of Biologic Material. J. Lab. and Clin. Med. 37: 621, 1951.

25. Taran, L. M., and Szilagyi, N.: The Duration of Electrical Systole (QT) in Acute Rheumatic Carditis in Children. Am. Heart J. 33: 14, 1947.

26. Pearson, C. M., and O'Meara, P. M.: An Electrocardiographic Study of Recurrent Hyperkalemia: Report of a Case. (To be published.)