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Potassium and Cardiac Surgery
Potassium and Cardiac Surgery A. K. Mandal, M.D., J. C. Callaghan, M.D., A. M. Dolan, M.Sc., and L. P. Sterns, M.D.
T
he importance of potassium in maintaining normal heart action has been known for a long time [15]. A fall in plasma potassium during cardiopulmonary bypass has been described by many workers [I, 2, 51, and the relationship between arrhythmias and low serum potassium levels has been described [6]. Such changes, unless immediately recognized and corrected, may affect the morbidity and mortality in cardiac patients. Normal plasma levels of potassium do not preclude the possibility of total body depletion [14]. This investigation was designed to determine the changes in potassium ion concentration both in patients who underwent cardiopulmonary bypass and in patients who did not.
MATERIALS A N D METHODS Seventy patients who underwent cardiopulmonary bypass were studied. Seventeen of these had congenital heart disease and 53 had acquired heart disease. Ages varied from 6 to 60 years. T h e bypass times varied between 20 and 120 minutes. Twenty patients who underwent closed mitral commissurotomy were studied for comparison. The Travenol disposable bubble oxygenator was used, with normothermic perfusion, in all cases. T h e priming volume was 20 ml. of Ringer’s lactate solution per kilogram of body weight. All patients with acquired heart disease received 25 gm. of mannitol in the priming solution. By the use of a mixture of 97% pure oxygen with 3% carbon dioxide and the administration of sodium bicarbonate in the system when indicated, significant changes in blood pH were avoided. Coronary perfusion was used in each case of aortic valve replacement. There was no cardioplegia in any of our cases. Patients did not receive digitalis or diuretics for 72 hours prior to operations. Patients who received diuretics in the postoperative period or who had a tracheostomy were excluded to avoid the adverse effects of hyperventilation [71. In most cases, the blood remaining in the pump after the end of bypass was returned to the patient. Citrated bank blood, one to three days old, was employed for replacement of blood loss. BLOOD AND URINE TESTS
Serum potassium determinations were made (1) preoperatively; (2) 3 to 5 hours postoperatively; (3) 24 hours postoperatively; (4) 48 hours postoperatively; and (5) 72 hours postoperatively. Arterial blood was analyzed for pH, PO*, pCOz, and H C 0 3 (1) just prior to bypass; (2) after every 20 minutes of bypass; and (3) at From the Division of Cardiovascular and Thoracic Surgery, University of Alberta Hospital, and the Surgical-Medical Research Institute, University of Alberta, Edmonton, Alberta, Canada. Supported by Alberta Heart Foundation grants 68-18 and 68-45. Presented at the Fifth Annual Meeting of The Society of Thoracic Surgeons, San Diego, Calif., Jan. 27-29, 1969. Address reprint requests to Dr. Callaghan, Chief, Division of Thoracic and Cardiovascular Surgery, University of Alberta Hospital, Edmonton, Alberta, Canada.
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Potassium and Cardiac Surgery the termination of bypass. Urine excretion and urine potassium concentration determinations were made (1) 24 hours preoperatively; (2) 48 hours postoperatively: and (3) 72 hours postoperatively. MYOCARDIAL AND SKELETAL TISSUE STUDIES
Myocardial and skeletal muscle biopsies were taken before and after bypass in patients who underwent cardiopulmonary bypass. Approximately 10 gm. of the rectus muscle or intercostal muscle was excised and carefully blotted free of blood; all fat and fibrous tissue were removed, and the muscle sample was then placed in a test tube for immediate transfer to the laboratory. Approximately 5 gm. of cardiac muscle was taken from the right atrial appendage. Tissue sodium and potassium were measured from fat-free, dry, solid tissue [lo]. RESULTS Table 1 shows that 4 patients (6%) in the extracorporeal circulation group (Group I) and 2 patients (10%)in the closed mitral commissurotomy group (Group 11) were within the hypokalemic range. Plasma potassium levels were often normal throughout the bypass, but 3 to 5 hours after the end of bypass, the plasma potassium level was commonly either about the same or lower than that obtained during bypass. Table 2 illustrates that the number of patients in the hypokalemic range rose to 16 (33%) in Group I; there was no change in the closed mitral commissurotomy group of patients. TABLE 1.
PREOPERATIVE PLASMA POTASSIUM
Total No. of Patients
Plasma Potassium Values (mEq./L.) 2.0-3.4
t
(Ranges) +
3.54.8
Extracorporeal circulation (Group I)
63
4 (6%) 3.25 Average (<2.9 mEq./L. in no patients)
59 (94%) 4.05 Average i>4.0 mEq./L. in 34 patients)
Closed mitral (Group 11)
19
2 (10%) 3.35 Average (<2.9 mEq./L. in no patients)
17 (90%) 4.00 Average (>4.0 mEq./L. in 7 patients)
TABLE 2.
PLASM.4 POTASSIUM 3 TO 5 HOURS AFTER THE END OF BYPASS
Total No. of Patients
Plasma Potassium Values (mEq./L.) 2.0-3.4
t
(Ranges) +
3.5-4.8
Extracorporeal circulation (Group I)
49
16 (33%) 3.14 Average (<2.9 mEq./L. in no patients)
33 (67%) 4.07 Average !>4.0 mEq./L. in 12 patients)
Closed mitral (Group 11)
10
1(10%) 2.9 Average (<2.9 mEq./L. in no patients)
9 (90%) 4.23 Average (>4.0 mEq./L. in 5 patients)
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MANDAL E T AL. Table 3 shows that in Group I, 10 (19%) and 13 (25%) patients remained hypokalemic on the second and third postoperative days, respectively. T h e number of patients in the closed mitral commissurotomy group did not alter in this respect. Table 4 points out that 17 (24%) of the patients in Group I lost less than 40 mEq. of potassium in the urine, with an average content of 62.3 mEq. per liter. Eight patients (40%) in Group I1 lost less than 40 mEq. per liter of potassium in the urine, with a n average content of 47.2 mEq. per liter. Table 5, based on 60 bypass patients, demonstrates that the average urine output was 221 ml., average potassium content was 52.8 mEq. per liter, and 20 patients (33%) lost less than 40 mEq. per liter of potassium. I n Group I, the average potassium concentration in the urine during bypass did not increase, but rather dropped by 9.5 mEq. per liter. TABLE 3. POSTOPERATIVE PLASMA POTASSIUM
__
-
No. of patients with Plasma Potassium (mEq./L.)
Total No. of Patients
24-48 hours 2.0-3.4
48-72 hours
3.5-4.8
+
(Ranges)
-,2.0-3.4
3.4-4.8
Extracorporeal circulation (Group I)
52
10 (19%) 3.01 Average (<2.9 mEq./L. in 1 patient)
42 (81%) 4.2 1 Average b4.0 mEq./L. in 29 patients)
13 (25%) 3.18 Average (<2.9 mEq. / L. in 2 patients)
39 (75%) 3.98 Average b4.0 mEq./L. in 13 patients)
Closed mitral (Group 11)
19
1(5%) 3.2 Average (<2.9 mEq./L. in no patients)
18 (95%) 4.25 Average b4.0 mEq./L. in 16 patients)
2 (11%) 3.18 Average (<2.9 mEq./L. in no patients)
17 (89%) 3.95 Average (>4.0 mEq./L. in 7 patients)
TABLE 4. PREOPERATIVE URINE VOLUME AND POTASSIUM CONTENT
24-Hour Urine Volume Passed Before Bypass
Potassium Content of Urine ~
No. of Patients
Average Volume and Range (ml.)
Average Potassium Content and Range (mEq./L.)
No. Patients with Less T h a n 40 mEq./L. Potassium
62.3 (16-1 70)
17 (24%)
47.2
8 (40%)
Ex tracorporeal circulation (Group I)
70
1339 (125-3450)
15 (21%)
Closed mitral (Group 11)
20
1314 (470-2790)
1 (570)
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~~~
No. Patients with Volume Less T h a n 700 ml.
( 14-94)
Potassium and Cardiac Surgeiy Urine was collected during three 24-hour periods, starting on the day after termination of the extracorporeal circulation in Group I and after termination of the operation in Group I1 cases. As shown in Table 6, the urine excretion rate decreased from 847 cc. to 626 cc. on the first postoperative day in Group I cases. This change was not noted in the Group I1 cases (Table 7). T h e greatest potassium loss in the urine was usually during the first 48 hours following operation. I n Group I, the greatest loss was during the second 24-hour period, while in Group I1 the greatest loss was in the first 24-hour period. I n Group I, 74% of the patients lost less than 100 mEq. per liter, as compared to 18% of Group 11. Moreover, in 55% of Group I1 cases, potassium loss was in the range of 100 to 150 mEq. per liter, in contrast to 19% in Group I cases. However, almost all patients in both groups excreted less than 100 mEq. per liter of potassium by 72 hours after operation. Average potassium content at that time in Group I cases was 52.5 mEq. per liter; in Group I1 cases, it was 35.1 mEq. per liter. Prebypass and postbypass myocardial biopsies were taken on 40 patients and skeletal muscle biopsies on 11 patients [131 (Figs. 1, 2). With only minimal pH changes, tissue potassium fell and tissue sodium rose. T h e average sodium and potassium difference between prebypass and postbypass in myocardial tissue is +7.7 and -5.1 mEq. per 100 gm.of fat-free dry tissue, respectively. Table 8 shows the arrhythmias that developed in our cases. Arrhythmias TABLE 5. URINE VOLUME AND POTASSIUM CONTENT DURING BYPASS
Volume of Urine Passed During Bypass
No. of Patients
60
Potassium Content of Urine -
Average Volume and Range (ml.)
Average Potassium Content and Range (mEq./L.)
No. of Patients with Less T h a n 40 mEq./L. Potassium
22 1 (22-960)
52.8 (18-1 68)
20 (33%)
.~
T.4BI.E 6. URINE EXCRETION AND POTASSIUM LOSS IN T H E P09TOPERATiVE PERIOD FOLLOWING EXTRACORPOREAL CIRCULATION
24-Hour Urine Collections &24 Hours No. of patients
Average volume of urine (ml.) Average potassium content and range (mEq./L.) No. of patients excreting less than 80 mEq. K/L. No. of patients excreting less than 100 mEq. K/L.
No. of patients excreting 100-150 mEq. KIL. No. of patients excreting more than 150 mEq. K/L.
66
24-48 Hours 48-72 Hours
38 (58%)
63 626 80.2 (8-1 32) 28 (44%)
49 (74%)
42 (67%)
13 (19%)
21 (33%)
847 52.5 ( 1 8-1 65)
4 (7%)
0
58 869 82.0 (5- 114) 56 (96%) 57 (98%)
0
MANDAL E T AL. TABLE 7. URINE VOLUME AND POTASSIUM LOSS IN POSTOPERATIVE PERIOD (CLOSED MITRAL-CROUP 11)
24-Hour Urine Collections 0-24 Hours 24-48 Hours 48-72 Hours
No. of patients Average volume of urine (ml.) Average K content and range (mEq./L.) No. of patients excreting less than 100 mEq. K/L. No. of patients excreting 100-150 mEq. K/L.
22 532
22 537
20 701
124.7 (36-1 80) 4 (18%)
74.5 (2 1-1 32) 18 (82%)
35.1 (8-70) 20 (100%)
12 (55%)
4 (18%)
0
0
0
No. of patients excreting more than 150 mEq. K/L.
6 (27%)
varied from ventricular irritability and nodal rhythm to atrial fibrillation. None of these patients had electrocardiographic evidence of hypokalemia. Arrhythmias were prevalent in the acquired disease group, both in preoperative and postoperative periods. Seventeen percent of the extracorporeal group had preoperative arrhythmias; 50% of this group developed some kind of arrhythmia in the postoperative period. There was only a 5% increase in the percentage of arrhythmias for the closed mitral commissurotomy patients.
FIG. 1 . Preoperative and postoperative diflerences in myocardial sodium concentration levels in individual patients; intracellular sodium before and after bypass. 432
T H E ANNALS OF THORACIC SURGERY
Potassium and Cardiac Surgery
F I G . 2.
Intracellular potassium before and after bypass. TABLE 8. PREOPERATIVE AND POSTOPERATIVE ARRHYTHMIAS
No. of Patients
70 20
Extracorporeal (Group I) Closed mitral (Group 11) -
.
~
-
Preoperative Arrhythmias
Postoperative Arrhythmias
No.
%
No.
%
12 4
20
17
35 5
50 25
COMMENT
It was noticed that the plasma potassium level in the range of 3.0 mEq. per liter, 3 to 5 hours after the end of bypass, changed from 6% to 33% of the cases; 19% to 25% of the cases still remained in that range u p to 72 hours. This type of change was not noticed in closed mitral comm issurotomy groups. Urinary potassium loss was usually greatest on the day of operation and the first postoperative day in both series. As indicated previously, this loss was marked in closed mitral commissurotomy cases. T h e major causes of potassium excretion in the postoperative period are stress, diuresis, hernodilution, and improvement in the cardiovascular state. It is difficult to explain the high urinary potassium excretion present in Group I1 cases. However, one might postulate that there was total deVOL.
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MANDAL E T AL.
pletion of body potassium in the extracorporeal group of patients. Potassium, the primary intracellular cation, declines with loss of cell mass and in sickness. Part of the loss may be due to abnormalities of cell metabolism [ 123. The concept of hemodilution has been introduced clinically. T h e patient must excrete this large water load, and, as in the postoperative period, the urine contains large amounts of potassium. Excessive diuresis is undesirable and was prevented by restricting the intravenous fluid. Muscle biopsy revealed that there was a decrease in potassium ion concentration within the myocardial and skeletal muscle cell, whereas there was corresponding increase of sodium ion concentration within the same cell [ 131. During cardiopulmonary bypass, there was depletion of intracellular potassium from both the myocardial and skeletal tissue. One might postulate that this change could be due to (1) disruption of active transport of sodium and potassium due to alterations in pump mechanisms; (2) intracellular accumulation of hydrogen ions [l 11; or (3) change in extracellular pH [3, 4,9, 161. Intracellular hydrogen ion concentration was not measured in our cases. However, the extracellular pH change was minimal, except in 4 cases in which intracellular efflux of potassium and influx of sodium ion were noticed. Thus, one might conclude that there is further total body depletion of potassium due to disruption of intracellular potassium and increase of potassium during and after bypass. It has been suspected that a combination of hyperglycemia, increased urinary loss of potassium, and hemodilution produces low plasma potassium levels. In addition to these factors, however, we think that there is another factor that contributes to the low plasma potassium level. After bypass, the extracellular K + enters the cells as the body’s homeostatic mechanisms begin to act. Then the fall in plasma potassium 3 to 5 hours after the end of bypass is the result of redistribution of this ion [Z]. The pathogenesis and mechanisms of arrhythmias have not yet been entirely clarified [8]. There are many causes of arrhythmias other than hypokalemia in the postoperative period. It is interesting to note that only 33% of the patients who developed arrhythmias were in the hypokalemic range. As previously stated, this is the same overall percentage of patients who were in the hypokalemic range. None of the plasma potassium values fell below 2.9 mEq. per liter. In the postoperative period, if a patient excreted potassium in the range of 80 to 125 mEq. per liter, plasma potassium values were studied more frequently. No relation was found between the amount of potassium excreted in the urine and the occurrence of arrhythmias. Of the patients who developed arrhythmias, 56% had an excretion of urinary potassium on the second day of more than 80 mEq. per liter. T h e same 434
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Potassium and Cardiac Surgery
percentage of all patients were in that range. It is not possible to give an arbitrary dose of potassium based on urine volume and potassium excretion of urine. SUMMARY
T h e role of potassium during open-heart surgery by normotherniia bypass techniques, primarily with use of hemodilution and the Travenol disposable bubble oxygenator, has been investigated in 70 patients and compared with 20 patients who underwent closed mitral commissurotomy. Despite the use of Ringer's lactate solution (which contains 40 mEq. of KCl per liter) for hemodilution, the plasma potassium level 3 to 5 hours after bypass fell to hypokalemic levels in onethird of the patients. Urinary potassium excretion was also increased during the postoperative period in both groups of patients, and was more marked in the patients undergoing closed mitral commissurotomy. Biopsy of myocardial and skeletal muscle revealed a decrease in intracellular potassium and an increase in intracellular sodium content after the bypass. In addition to other causes, the fall in plasma potassium is the result of a redistribution of this ion after the bypass. A C K N O WL-EDGMENTS T h e authors would like to thank the staffs of Room, and Cardiovascular and Thoracic Surgery Mr. Dietricli Kemna and Mr. Danny Johnston; Laboratory, who have collected and analyzed the
the Theatre, Cardiac Recovery Ward; the Pump Technicians, and the staff of Biochemistry samples for us.
REFERENCES 1. Barnard, M. S., Saunders, S. J . , Eales, L., and Barnard, C. N. Hypokalemia during extracorporeal circulation. Lancet 1 :240, 1966. 2. Barnard, M. S., Saunders, S. J., Eales, L., and Barnard, C. N. Hypokalemia during extracorporeal circu!ation: An experimental study. Afr. M c d . J. 40:
1132, 1966. 3. Belsa, E. S., GonzaleL, M. G., and Gingolani, H. E. Early increase of potassium in hyperventilation. A m e r . J. Physiol. 208:537, 1965. 4. Burnell, J. M., and Scribner, B. H . Interpretation of the serum potassium concentration in patients with acid-base imbalance. Surg. Forum 7:71, 1956. 5. DeWall, R. A.. and Lillehei, C. W. Simplified total body perfusion. J . A . M . A . 179:430, 1962. 6. Ebert, P. A., Jude, J. R., and Gaertner, R. A. Hypokalemia following open heart surgery in patients on long term diuretic therapy. Circulation 30 (Suppl. 3):71, 1964. 7. Flemma, R. J., and Young, W. G., Jr. T h e metabolic effects of mechanical ventilation and respiratory alkalosis in post-operative patients. Surgery 56:36, 1964. 8. Fujita, T. Experimental study on relationship between the evidence of atrial fibrillation and electrolytes in serum. J a p . Circ. J. 31:381, 1967.
MANDAL E T AL. 9. Krasna, I. H., Shuster, M., Baens, H., Kreel, I., and Baronofsky, I. D. A study of acid-base and electrolyte derangements after prolonged cardiopulmonary by-pass. J. Thorac. Cardiovasc. Surg. 42:244, 1961. 10. Litchfield, J. A., and Gaddie, R. E. Measurement of the phase distribution of water and electrolytes in skeletal muscles by the analysis of small samples. Clin. Sci. 17:483, 1958. 11. Litwin, M. S., Panico, F. B., Rubini, C., Harken, D. E., and Moore, F. D. Acidosis and lacticacidemia in extracorporeal circulation: T h e significance of perfusion flow rate and relation to perfusion respiratory alkalosis. A n n . Surg. 119: 188, 1959. 12. Lockey, E., Ross, D. N., Longmore, D. B., and Sturridge, M. F. Potassium and open heart surgery. Lancet 1:671, 1966. 13. Mandal, A, K., Callaghan, J. C., and Sterns, L. P. Changes in intracellular potassium resulting from extracorporeal circulation. Surg. Forum 19: 137, 1968. 14. Moore, F. D. Determination of total body water and solids with isotopes. Science (N.Y.) 104:157, 1946. 15. Ringer, S., and Murrell, W. Concerning the effects on frogs of arrest of the circulation and an explanation of the action of potash salts on the animal body. J. Physiol. (London) 1:72, 1878. 16. Simmons, D., and Avedon, M. Acid-base alterations and plasma potassium concentration. Amer. J. Physiol. 197:319, 1959.
DISCUSSION DR. WILLIAME. NEVILLE(Hines, Ill.): My associates, Dr. Raymond Dieter and Dr. Roque PifarrC, and I have just reviewed the alterations in serum potassium in 75 patients who underwent open-heart surgery. I am amazed by the striking similarity between Dr. Mandal’s results and ours. As everyone would agree, in the digitalized heart patient, hypokalemia can be devastating because of its propensity to cause cardiac arrhythmias. In reviewing our data we formulated the various routes by which potassium ion was lost from the serum: (1) All the open-heart patients have been on prolonged preoperative diuretic therapy which causes a considerable amount of potassium ion to be excreted in the urine before and after surgery. (2) Prior to bypass, hyperventilation by the anesthesiologist produces respiratory alkalosis with diffusion of potassium ion into the cell. (3) During bypass potassium ion is excreted in the urine and also diffuses into the cell. (4) In addition, the combination of a low potassium ion and a high sodium ion content of Ringer’s lactate, which is used for total prime of the disc oxygenator, results in an increased secretion of potassium ion in the urine with no offsetting replacement. (5) Again in the postoperative period the use of a mechanical ventilator for 24 hours causes respiratory alkalosis with more potassium ion entering the cell and later being excreted. T o prevent severe hypokalemia we now discontinue digitalis and diuretics at least three days before surgery. Frequent determinations of acid-base balance as well as of serum electrolytes are performed. Respiratory alkalosis is prevented by intermittent mechanical ventilation, and the 24-hour potassium ion content of the urine is measured. Since we know that a potassium ion deficiency exists in the pump prime, and hypokalemia is usually inevitable, we slowly add 30 mEq of potassium ion to the oxygenator during bypass. By following this regimen, we have had no documented hypokalemic-induced arrhythmias after open-heart surgery. DK. WILLIAME. OSTERMILLER, JR. (Oak Park, Ill.): We had the opportunity at Presbyterian-St. Luke’s Hospital in Chicago to care for a 33-year-old patient
436
THE ANNALS OF THORACIC SURGERY
Potassium and Cardiac Surgery who required aortic- and mitral-valve replacement. She illustrates the massive urine-potassium losses (625 mEq every 24 hours) sustained during and following surgery. Despite concomitant potassium infusion, it was difficult to keep the serum potassium in the normal range. This case prompted us to study a series of patients whose potassium losses were measured before, during, and following hemodilution cardiopulmonary bypass. Measurements were obtained every four hours. Striking serum- and urinepotassium losses were noted during surgery and in the early postoperative period. T h e elevation of the serum potassium at the twelfth postoperative hour corresponded to endotracheal extubation with cessation of mechanical ventilation. We agree with Dr. Neville’s summary of causes of hypopotassemia. Anticipation of potassium deficits, frequent potassium monitoring, and adequate s u p plementation have helped to decrease the frequency of cardiac arrythmias in our patients. DR. ROBERT L. T A Y L O R (Dayton, Ohio): Dr. Richard DeWall and I have been interested in the potassium metabolism of 40 of his open-heart patients. We have attempted to demonstrate that there may be some correlation between the potassium level in the serum and the serum carbon dioxide. In our experience, the serum potassium may be normal preoperatively; but, we noticed that there was a significant elevation in the preoperative serum carbon dioxide which did not exist in the postoperative phase. We believe that even though the serum potassium may be normal, the cellular potassium may actually be depleted. Many fourth-stage patients, because of their prolonged medical management, may come to operation with an actual total-body intracellular potassium deficit. Because of this, we have maintained these patients on a regimen of high potassium intake for a week to ten days prior to operation. This would seem the minimum time necessary to give these patients an overload. We have given them up to 50 to 150 mEq of potassium supplement daily, and this seems to have cut down on the postoperative arrhythmias. We have not worried about stopping digitalis a few days preoperatively and have not experienced any hypokalemia or digitalis intoxication in the postoperative phase. DR. SHELDON BURMAN (New York, N.Y.): It would be necessary, in order to evaluate these results, to know what was the relative difference between the two groups of patients in the amount of blood transfusion received before, during, and after operation. If large amounts of banked blood were used with its known high potassium level, this would certainly make a difference, particularly since they were so careful in measuring postoperative potassium in the blood at close intervals. In order to obtain meaningful results, I think it would be necessary to have some kind of control in which the two groups of patients had reasonably similar blood transfusions. I wonder if they would comment on that. DR. MANDAL (E,dmonton, Alberta, Canada): We do not use any blood in the bubble oxygenator a s a priming solution. We always replace the amount of blood drained out of the chest tubes. We do not do any blood volume studies. Both of these groups received the volume of blood that they drained through the chest tubes. T o eliminate the various factors causing loss of potassium, I have taken only 63 patients who had neither tracheostomy nor any mechanical ventilatory support. Moreover, all patients were taken off digitalis and/or diuretics more than 72 hours prior to operation. It is known that in alkalosis the potassium goes inside the cell. Also, it has been reported that HCO, is a most important determinant of acidosis. But our studies show that there is an approximate correlation between A HCO, and A pH. I n this investigation we see the patients lose potassium from the cell even in the face of alkalosis. Thus, we think that there is some other mechanism.
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T
he importance of potassium in maintaining normal heart action has been known for a long time [15]. A fall in plasma potassium during cardiopulmonary bypass has been described by many workers [I, 2, 51, and the relationship between arrhythmias and low serum potassium levels has been described [6]. Such changes, unless immediately recognized and corrected, may affect the morbidity and mortality in cardiac patients. Normal plasma levels of potassium do not preclude the possibility of total body depletion [14]. This investigation was designed to determine the changes in potassium ion concentration both in patients who underwent cardiopulmonary bypass and in patients who did not.
MATERIALS A N D METHODS Seventy patients who underwent cardiopulmonary bypass were studied. Seventeen of these had congenital heart disease and 53 had acquired heart disease. Ages varied from 6 to 60 years. T h e bypass times varied between 20 and 120 minutes. Twenty patients who underwent closed mitral commissurotomy were studied for comparison. The Travenol disposable bubble oxygenator was used, with normothermic perfusion, in all cases. T h e priming volume was 20 ml. of Ringer’s lactate solution per kilogram of body weight. All patients with acquired heart disease received 25 gm. of mannitol in the priming solution. By the use of a mixture of 97% pure oxygen with 3% carbon dioxide and the administration of sodium bicarbonate in the system when indicated, significant changes in blood pH were avoided. Coronary perfusion was used in each case of aortic valve replacement. There was no cardioplegia in any of our cases. Patients did not receive digitalis or diuretics for 72 hours prior to operations. Patients who received diuretics in the postoperative period or who had a tracheostomy were excluded to avoid the adverse effects of hyperventilation [71. In most cases, the blood remaining in the pump after the end of bypass was returned to the patient. Citrated bank blood, one to three days old, was employed for replacement of blood loss. BLOOD AND URINE TESTS
Serum potassium determinations were made (1) preoperatively; (2) 3 to 5 hours postoperatively; (3) 24 hours postoperatively; (4) 48 hours postoperatively; and (5) 72 hours postoperatively. Arterial blood was analyzed for pH, PO*, pCOz, and H C 0 3 (1) just prior to bypass; (2) after every 20 minutes of bypass; and (3) at From the Division of Cardiovascular and Thoracic Surgery, University of Alberta Hospital, and the Surgical-Medical Research Institute, University of Alberta, Edmonton, Alberta, Canada. Supported by Alberta Heart Foundation grants 68-18 and 68-45. Presented at the Fifth Annual Meeting of The Society of Thoracic Surgeons, San Diego, Calif., Jan. 27-29, 1969. Address reprint requests to Dr. Callaghan, Chief, Division of Thoracic and Cardiovascular Surgery, University of Alberta Hospital, Edmonton, Alberta, Canada.
428
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Potassium and Cardiac Surgery the termination of bypass. Urine excretion and urine potassium concentration determinations were made (1) 24 hours preoperatively; (2) 48 hours postoperatively: and (3) 72 hours postoperatively. MYOCARDIAL AND SKELETAL TISSUE STUDIES
Myocardial and skeletal muscle biopsies were taken before and after bypass in patients who underwent cardiopulmonary bypass. Approximately 10 gm. of the rectus muscle or intercostal muscle was excised and carefully blotted free of blood; all fat and fibrous tissue were removed, and the muscle sample was then placed in a test tube for immediate transfer to the laboratory. Approximately 5 gm. of cardiac muscle was taken from the right atrial appendage. Tissue sodium and potassium were measured from fat-free, dry, solid tissue [lo]. RESULTS Table 1 shows that 4 patients (6%) in the extracorporeal circulation group (Group I) and 2 patients (10%)in the closed mitral commissurotomy group (Group 11) were within the hypokalemic range. Plasma potassium levels were often normal throughout the bypass, but 3 to 5 hours after the end of bypass, the plasma potassium level was commonly either about the same or lower than that obtained during bypass. Table 2 illustrates that the number of patients in the hypokalemic range rose to 16 (33%) in Group I; there was no change in the closed mitral commissurotomy group of patients. TABLE 1.
PREOPERATIVE PLASMA POTASSIUM
Total No. of Patients
Plasma Potassium Values (mEq./L.) 2.0-3.4
t
(Ranges) +
3.54.8
Extracorporeal circulation (Group I)
63
4 (6%) 3.25 Average (<2.9 mEq./L. in no patients)
59 (94%) 4.05 Average i>4.0 mEq./L. in 34 patients)
Closed mitral (Group 11)
19
2 (10%) 3.35 Average (<2.9 mEq./L. in no patients)
17 (90%) 4.00 Average (>4.0 mEq./L. in 7 patients)
TABLE 2.
PLASM.4 POTASSIUM 3 TO 5 HOURS AFTER THE END OF BYPASS
Total No. of Patients
Plasma Potassium Values (mEq./L.) 2.0-3.4
t
(Ranges) +
3.5-4.8
Extracorporeal circulation (Group I)
49
16 (33%) 3.14 Average (<2.9 mEq./L. in no patients)
33 (67%) 4.07 Average !>4.0 mEq./L. in 12 patients)
Closed mitral (Group 11)
10
1(10%) 2.9 Average (<2.9 mEq./L. in no patients)
9 (90%) 4.23 Average (>4.0 mEq./L. in 5 patients)
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MANDAL E T AL. Table 3 shows that in Group I, 10 (19%) and 13 (25%) patients remained hypokalemic on the second and third postoperative days, respectively. T h e number of patients in the closed mitral commissurotomy group did not alter in this respect. Table 4 points out that 17 (24%) of the patients in Group I lost less than 40 mEq. of potassium in the urine, with an average content of 62.3 mEq. per liter. Eight patients (40%) in Group I1 lost less than 40 mEq. per liter of potassium in the urine, with a n average content of 47.2 mEq. per liter. Table 5, based on 60 bypass patients, demonstrates that the average urine output was 221 ml., average potassium content was 52.8 mEq. per liter, and 20 patients (33%) lost less than 40 mEq. per liter of potassium. I n Group I, the average potassium concentration in the urine during bypass did not increase, but rather dropped by 9.5 mEq. per liter. TABLE 3. POSTOPERATIVE PLASMA POTASSIUM
__
-
No. of patients with Plasma Potassium (mEq./L.)
Total No. of Patients
24-48 hours 2.0-3.4
48-72 hours
3.5-4.8
+
(Ranges)
-,2.0-3.4
3.4-4.8
Extracorporeal circulation (Group I)
52
10 (19%) 3.01 Average (<2.9 mEq./L. in 1 patient)
42 (81%) 4.2 1 Average b4.0 mEq./L. in 29 patients)
13 (25%) 3.18 Average (<2.9 mEq. / L. in 2 patients)
39 (75%) 3.98 Average b4.0 mEq./L. in 13 patients)
Closed mitral (Group 11)
19
1(5%) 3.2 Average (<2.9 mEq./L. in no patients)
18 (95%) 4.25 Average b4.0 mEq./L. in 16 patients)
2 (11%) 3.18 Average (<2.9 mEq./L. in no patients)
17 (89%) 3.95 Average (>4.0 mEq./L. in 7 patients)
TABLE 4. PREOPERATIVE URINE VOLUME AND POTASSIUM CONTENT
24-Hour Urine Volume Passed Before Bypass
Potassium Content of Urine ~
No. of Patients
Average Volume and Range (ml.)
Average Potassium Content and Range (mEq./L.)
No. Patients with Less T h a n 40 mEq./L. Potassium
62.3 (16-1 70)
17 (24%)
47.2
8 (40%)
Ex tracorporeal circulation (Group I)
70
1339 (125-3450)
15 (21%)
Closed mitral (Group 11)
20
1314 (470-2790)
1 (570)
430
T H E ANNALS OF THORACIC SURGERY
~~~
No. Patients with Volume Less T h a n 700 ml.
( 14-94)
Potassium and Cardiac Surgeiy Urine was collected during three 24-hour periods, starting on the day after termination of the extracorporeal circulation in Group I and after termination of the operation in Group I1 cases. As shown in Table 6, the urine excretion rate decreased from 847 cc. to 626 cc. on the first postoperative day in Group I cases. This change was not noted in the Group I1 cases (Table 7). T h e greatest potassium loss in the urine was usually during the first 48 hours following operation. I n Group I, the greatest loss was during the second 24-hour period, while in Group I1 the greatest loss was in the first 24-hour period. I n Group I, 74% of the patients lost less than 100 mEq. per liter, as compared to 18% of Group 11. Moreover, in 55% of Group I1 cases, potassium loss was in the range of 100 to 150 mEq. per liter, in contrast to 19% in Group I cases. However, almost all patients in both groups excreted less than 100 mEq. per liter of potassium by 72 hours after operation. Average potassium content at that time in Group I cases was 52.5 mEq. per liter; in Group I1 cases, it was 35.1 mEq. per liter. Prebypass and postbypass myocardial biopsies were taken on 40 patients and skeletal muscle biopsies on 11 patients [131 (Figs. 1, 2). With only minimal pH changes, tissue potassium fell and tissue sodium rose. T h e average sodium and potassium difference between prebypass and postbypass in myocardial tissue is +7.7 and -5.1 mEq. per 100 gm.of fat-free dry tissue, respectively. Table 8 shows the arrhythmias that developed in our cases. Arrhythmias TABLE 5. URINE VOLUME AND POTASSIUM CONTENT DURING BYPASS
Volume of Urine Passed During Bypass
No. of Patients
60
Potassium Content of Urine -
Average Volume and Range (ml.)
Average Potassium Content and Range (mEq./L.)
No. of Patients with Less T h a n 40 mEq./L. Potassium
22 1 (22-960)
52.8 (18-1 68)
20 (33%)
.~
T.4BI.E 6. URINE EXCRETION AND POTASSIUM LOSS IN T H E P09TOPERATiVE PERIOD FOLLOWING EXTRACORPOREAL CIRCULATION
24-Hour Urine Collections &24 Hours No. of patients
Average volume of urine (ml.) Average potassium content and range (mEq./L.) No. of patients excreting less than 80 mEq. K/L. No. of patients excreting less than 100 mEq. K/L.
No. of patients excreting 100-150 mEq. KIL. No. of patients excreting more than 150 mEq. K/L.
66
24-48 Hours 48-72 Hours
38 (58%)
63 626 80.2 (8-1 32) 28 (44%)
49 (74%)
42 (67%)
13 (19%)
21 (33%)
847 52.5 ( 1 8-1 65)
4 (7%)
0
58 869 82.0 (5- 114) 56 (96%) 57 (98%)
0
MANDAL E T AL. TABLE 7. URINE VOLUME AND POTASSIUM LOSS IN POSTOPERATIVE PERIOD (CLOSED MITRAL-CROUP 11)
24-Hour Urine Collections 0-24 Hours 24-48 Hours 48-72 Hours
No. of patients Average volume of urine (ml.) Average K content and range (mEq./L.) No. of patients excreting less than 100 mEq. K/L. No. of patients excreting 100-150 mEq. K/L.
22 532
22 537
20 701
124.7 (36-1 80) 4 (18%)
74.5 (2 1-1 32) 18 (82%)
35.1 (8-70) 20 (100%)
12 (55%)
4 (18%)
0
0
0
No. of patients excreting more than 150 mEq. K/L.
6 (27%)
varied from ventricular irritability and nodal rhythm to atrial fibrillation. None of these patients had electrocardiographic evidence of hypokalemia. Arrhythmias were prevalent in the acquired disease group, both in preoperative and postoperative periods. Seventeen percent of the extracorporeal group had preoperative arrhythmias; 50% of this group developed some kind of arrhythmia in the postoperative period. There was only a 5% increase in the percentage of arrhythmias for the closed mitral commissurotomy patients.
FIG. 1 . Preoperative and postoperative diflerences in myocardial sodium concentration levels in individual patients; intracellular sodium before and after bypass. 432
T H E ANNALS OF THORACIC SURGERY
Potassium and Cardiac Surgery
F I G . 2.
Intracellular potassium before and after bypass. TABLE 8. PREOPERATIVE AND POSTOPERATIVE ARRHYTHMIAS
No. of Patients
70 20
Extracorporeal (Group I) Closed mitral (Group 11) -
.
~
-
Preoperative Arrhythmias
Postoperative Arrhythmias
No.
%
No.
%
12 4
20
17
35 5
50 25
COMMENT
It was noticed that the plasma potassium level in the range of 3.0 mEq. per liter, 3 to 5 hours after the end of bypass, changed from 6% to 33% of the cases; 19% to 25% of the cases still remained in that range u p to 72 hours. This type of change was not noticed in closed mitral comm issurotomy groups. Urinary potassium loss was usually greatest on the day of operation and the first postoperative day in both series. As indicated previously, this loss was marked in closed mitral commissurotomy cases. T h e major causes of potassium excretion in the postoperative period are stress, diuresis, hernodilution, and improvement in the cardiovascular state. It is difficult to explain the high urinary potassium excretion present in Group I1 cases. However, one might postulate that there was total deVOL.
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MANDAL E T AL.
pletion of body potassium in the extracorporeal group of patients. Potassium, the primary intracellular cation, declines with loss of cell mass and in sickness. Part of the loss may be due to abnormalities of cell metabolism [ 123. The concept of hemodilution has been introduced clinically. T h e patient must excrete this large water load, and, as in the postoperative period, the urine contains large amounts of potassium. Excessive diuresis is undesirable and was prevented by restricting the intravenous fluid. Muscle biopsy revealed that there was a decrease in potassium ion concentration within the myocardial and skeletal muscle cell, whereas there was corresponding increase of sodium ion concentration within the same cell [ 131. During cardiopulmonary bypass, there was depletion of intracellular potassium from both the myocardial and skeletal tissue. One might postulate that this change could be due to (1) disruption of active transport of sodium and potassium due to alterations in pump mechanisms; (2) intracellular accumulation of hydrogen ions [l 11; or (3) change in extracellular pH [3, 4,9, 161. Intracellular hydrogen ion concentration was not measured in our cases. However, the extracellular pH change was minimal, except in 4 cases in which intracellular efflux of potassium and influx of sodium ion were noticed. Thus, one might conclude that there is further total body depletion of potassium due to disruption of intracellular potassium and increase of potassium during and after bypass. It has been suspected that a combination of hyperglycemia, increased urinary loss of potassium, and hemodilution produces low plasma potassium levels. In addition to these factors, however, we think that there is another factor that contributes to the low plasma potassium level. After bypass, the extracellular K + enters the cells as the body’s homeostatic mechanisms begin to act. Then the fall in plasma potassium 3 to 5 hours after the end of bypass is the result of redistribution of this ion [Z]. The pathogenesis and mechanisms of arrhythmias have not yet been entirely clarified [8]. There are many causes of arrhythmias other than hypokalemia in the postoperative period. It is interesting to note that only 33% of the patients who developed arrhythmias were in the hypokalemic range. As previously stated, this is the same overall percentage of patients who were in the hypokalemic range. None of the plasma potassium values fell below 2.9 mEq. per liter. In the postoperative period, if a patient excreted potassium in the range of 80 to 125 mEq. per liter, plasma potassium values were studied more frequently. No relation was found between the amount of potassium excreted in the urine and the occurrence of arrhythmias. Of the patients who developed arrhythmias, 56% had an excretion of urinary potassium on the second day of more than 80 mEq. per liter. T h e same 434
THE ANNALS OF THOKACIC suKGEnY
Potassium and Cardiac Surgery
percentage of all patients were in that range. It is not possible to give an arbitrary dose of potassium based on urine volume and potassium excretion of urine. SUMMARY
T h e role of potassium during open-heart surgery by normotherniia bypass techniques, primarily with use of hemodilution and the Travenol disposable bubble oxygenator, has been investigated in 70 patients and compared with 20 patients who underwent closed mitral commissurotomy. Despite the use of Ringer's lactate solution (which contains 40 mEq. of KCl per liter) for hemodilution, the plasma potassium level 3 to 5 hours after bypass fell to hypokalemic levels in onethird of the patients. Urinary potassium excretion was also increased during the postoperative period in both groups of patients, and was more marked in the patients undergoing closed mitral commissurotomy. Biopsy of myocardial and skeletal muscle revealed a decrease in intracellular potassium and an increase in intracellular sodium content after the bypass. In addition to other causes, the fall in plasma potassium is the result of a redistribution of this ion after the bypass. A C K N O WL-EDGMENTS T h e authors would like to thank the staffs of Room, and Cardiovascular and Thoracic Surgery Mr. Dietricli Kemna and Mr. Danny Johnston; Laboratory, who have collected and analyzed the
the Theatre, Cardiac Recovery Ward; the Pump Technicians, and the staff of Biochemistry samples for us.
REFERENCES 1. Barnard, M. S., Saunders, S. J . , Eales, L., and Barnard, C. N. Hypokalemia during extracorporeal circulation. Lancet 1 :240, 1966. 2. Barnard, M. S., Saunders, S. J., Eales, L., and Barnard, C. N. Hypokalemia during extracorporeal circu!ation: An experimental study. Afr. M c d . J. 40:
1132, 1966. 3. Belsa, E. S., GonzaleL, M. G., and Gingolani, H. E. Early increase of potassium in hyperventilation. A m e r . J. Physiol. 208:537, 1965. 4. Burnell, J. M., and Scribner, B. H . Interpretation of the serum potassium concentration in patients with acid-base imbalance. Surg. Forum 7:71, 1956. 5. DeWall, R. A.. and Lillehei, C. W. Simplified total body perfusion. J . A . M . A . 179:430, 1962. 6. Ebert, P. A., Jude, J. R., and Gaertner, R. A. Hypokalemia following open heart surgery in patients on long term diuretic therapy. Circulation 30 (Suppl. 3):71, 1964. 7. Flemma, R. J., and Young, W. G., Jr. T h e metabolic effects of mechanical ventilation and respiratory alkalosis in post-operative patients. Surgery 56:36, 1964. 8. Fujita, T. Experimental study on relationship between the evidence of atrial fibrillation and electrolytes in serum. J a p . Circ. J. 31:381, 1967.
MANDAL E T AL. 9. Krasna, I. H., Shuster, M., Baens, H., Kreel, I., and Baronofsky, I. D. A study of acid-base and electrolyte derangements after prolonged cardiopulmonary by-pass. J. Thorac. Cardiovasc. Surg. 42:244, 1961. 10. Litchfield, J. A., and Gaddie, R. E. Measurement of the phase distribution of water and electrolytes in skeletal muscles by the analysis of small samples. Clin. Sci. 17:483, 1958. 11. Litwin, M. S., Panico, F. B., Rubini, C., Harken, D. E., and Moore, F. D. Acidosis and lacticacidemia in extracorporeal circulation: T h e significance of perfusion flow rate and relation to perfusion respiratory alkalosis. A n n . Surg. 119: 188, 1959. 12. Lockey, E., Ross, D. N., Longmore, D. B., and Sturridge, M. F. Potassium and open heart surgery. Lancet 1:671, 1966. 13. Mandal, A, K., Callaghan, J. C., and Sterns, L. P. Changes in intracellular potassium resulting from extracorporeal circulation. Surg. Forum 19: 137, 1968. 14. Moore, F. D. Determination of total body water and solids with isotopes. Science (N.Y.) 104:157, 1946. 15. Ringer, S., and Murrell, W. Concerning the effects on frogs of arrest of the circulation and an explanation of the action of potash salts on the animal body. J. Physiol. (London) 1:72, 1878. 16. Simmons, D., and Avedon, M. Acid-base alterations and plasma potassium concentration. Amer. J. Physiol. 197:319, 1959.
DISCUSSION DR. WILLIAME. NEVILLE(Hines, Ill.): My associates, Dr. Raymond Dieter and Dr. Roque PifarrC, and I have just reviewed the alterations in serum potassium in 75 patients who underwent open-heart surgery. I am amazed by the striking similarity between Dr. Mandal’s results and ours. As everyone would agree, in the digitalized heart patient, hypokalemia can be devastating because of its propensity to cause cardiac arrhythmias. In reviewing our data we formulated the various routes by which potassium ion was lost from the serum: (1) All the open-heart patients have been on prolonged preoperative diuretic therapy which causes a considerable amount of potassium ion to be excreted in the urine before and after surgery. (2) Prior to bypass, hyperventilation by the anesthesiologist produces respiratory alkalosis with diffusion of potassium ion into the cell. (3) During bypass potassium ion is excreted in the urine and also diffuses into the cell. (4) In addition, the combination of a low potassium ion and a high sodium ion content of Ringer’s lactate, which is used for total prime of the disc oxygenator, results in an increased secretion of potassium ion in the urine with no offsetting replacement. (5) Again in the postoperative period the use of a mechanical ventilator for 24 hours causes respiratory alkalosis with more potassium ion entering the cell and later being excreted. T o prevent severe hypokalemia we now discontinue digitalis and diuretics at least three days before surgery. Frequent determinations of acid-base balance as well as of serum electrolytes are performed. Respiratory alkalosis is prevented by intermittent mechanical ventilation, and the 24-hour potassium ion content of the urine is measured. Since we know that a potassium ion deficiency exists in the pump prime, and hypokalemia is usually inevitable, we slowly add 30 mEq of potassium ion to the oxygenator during bypass. By following this regimen, we have had no documented hypokalemic-induced arrhythmias after open-heart surgery. DK. WILLIAME. OSTERMILLER, JR. (Oak Park, Ill.): We had the opportunity at Presbyterian-St. Luke’s Hospital in Chicago to care for a 33-year-old patient
436
THE ANNALS OF THORACIC SURGERY
Potassium and Cardiac Surgery who required aortic- and mitral-valve replacement. She illustrates the massive urine-potassium losses (625 mEq every 24 hours) sustained during and following surgery. Despite concomitant potassium infusion, it was difficult to keep the serum potassium in the normal range. This case prompted us to study a series of patients whose potassium losses were measured before, during, and following hemodilution cardiopulmonary bypass. Measurements were obtained every four hours. Striking serum- and urinepotassium losses were noted during surgery and in the early postoperative period. T h e elevation of the serum potassium at the twelfth postoperative hour corresponded to endotracheal extubation with cessation of mechanical ventilation. We agree with Dr. Neville’s summary of causes of hypopotassemia. Anticipation of potassium deficits, frequent potassium monitoring, and adequate s u p plementation have helped to decrease the frequency of cardiac arrythmias in our patients. DR. ROBERT L. T A Y L O R (Dayton, Ohio): Dr. Richard DeWall and I have been interested in the potassium metabolism of 40 of his open-heart patients. We have attempted to demonstrate that there may be some correlation between the potassium level in the serum and the serum carbon dioxide. In our experience, the serum potassium may be normal preoperatively; but, we noticed that there was a significant elevation in the preoperative serum carbon dioxide which did not exist in the postoperative phase. We believe that even though the serum potassium may be normal, the cellular potassium may actually be depleted. Many fourth-stage patients, because of their prolonged medical management, may come to operation with an actual total-body intracellular potassium deficit. Because of this, we have maintained these patients on a regimen of high potassium intake for a week to ten days prior to operation. This would seem the minimum time necessary to give these patients an overload. We have given them up to 50 to 150 mEq of potassium supplement daily, and this seems to have cut down on the postoperative arrhythmias. We have not worried about stopping digitalis a few days preoperatively and have not experienced any hypokalemia or digitalis intoxication in the postoperative phase. DR. SHELDON BURMAN (New York, N.Y.): It would be necessary, in order to evaluate these results, to know what was the relative difference between the two groups of patients in the amount of blood transfusion received before, during, and after operation. If large amounts of banked blood were used with its known high potassium level, this would certainly make a difference, particularly since they were so careful in measuring postoperative potassium in the blood at close intervals. In order to obtain meaningful results, I think it would be necessary to have some kind of control in which the two groups of patients had reasonably similar blood transfusions. I wonder if they would comment on that. DR. MANDAL (E,dmonton, Alberta, Canada): We do not use any blood in the bubble oxygenator a s a priming solution. We always replace the amount of blood drained out of the chest tubes. We do not do any blood volume studies. Both of these groups received the volume of blood that they drained through the chest tubes. T o eliminate the various factors causing loss of potassium, I have taken only 63 patients who had neither tracheostomy nor any mechanical ventilatory support. Moreover, all patients were taken off digitalis and/or diuretics more than 72 hours prior to operation. It is known that in alkalosis the potassium goes inside the cell. Also, it has been reported that HCO, is a most important determinant of acidosis. But our studies show that there is an approximate correlation between A HCO, and A pH. I n this investigation we see the patients lose potassium from the cell even in the face of alkalosis. Thus, we think that there is some other mechanism.
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