Effect of ACD Blood Prime on Plasma

Transcription

1 Effect of ACD Blood Prime on Plasma Calcium and Magnesium Duncan A. Killen, M.D., Edwin L. Grogan, 11, M.D., Roland E. Gower, M.D., Isabella S. Collins, M.D., and Harold A. Collins, M.D. ABSTRACT The changes in the total plasma calcium, ionized calcium, total magnesium, and ionized magnesium during cardiopulmonary bypass were measured in 38 patients in whom acid citrate dextrose (ACD) preserved blood was used in the pumpoxygenator prime. The ionized calcium was measured directly using a calcium ion electrode. It was found that reconstitution of ACD blood with 10% calcium chloride in an amount equivalent to 8 ml. per unit of ACD blood resulted in a normal ionized calcium level in the plasma. There was severe depression of the ionized magnesium when ACD blood was used in the pump-oxygenator prime; however, addition of 10% magnesium sulfate in an amount of 3 ml. per unit of ACD blood returned the ionized magnesium to the normal range. T e use of ACD (acid citrate dextrose) preserved blood prime for cardiopulmonary bypass necessitates the addition of large amounts of calcium if severe depression of the plasma ionized calcium is to be avoided. Recently, a calcium ion electrode which measures plasma ionized calcium activity directly has become available, and this electrode was used to document the course of plasma ionized calcium during clinical cardiopulmonary bypass. The citrate of ACD solution has equal binding affinity for calcium and magnesium ions. From the simultaneous measurement of plasma total calcium, total magnesium, and ionized calcium, it was possible to calculate the ionized magnesium concentration also. Methods Measurements of plasma calcium and magnesium were performed in a consecutive series of 38 patients undergoing cardiopulmonary bypass at the Vanderbilt University Medical Center. The majority of the patients were adults undergoing prosthetic valve insertion for acquired valvular disease. Some patients were children who underwent correction of congenital cardiac defects. From the Division of Cardiothoracic Surgery, Vanderbilt University Medical Center, Nashville, Tenn. Accepted for publication Sept. 21, Address reprint requests to Dr. Killen. Department of Surgery, Vanderbilt University School of Medicine, Nashville, Tenn VOL. 13, NO. 4, APRIL,

2 KILLEN ET AL. TABLE 1. CONSTITUENTS OF PUMP-OXYGENATOR PRIME Material Amount Lactated Ringer's solution 1,000 ml. Mannitol 20% 250 ml. ACD blood 1,500 ml. Heparin 9,000 u. THAM 60 meq. Calcium chloride 10% 18 ml. Total volume 3,000 ml.*.approximately. THAM = trihydroxymethylaminomethane. Cardiopulmonary bypass was conducted using a roller pump' and a disposable oxygenator.? In most instances, mild hypothermia (30' to 32 C.) was utilized during the intracardiac portion of the procedure. The pump-oxygenator prime consisted of ACD banked blood plus approximately an equal volume of nonblood additives. In adults, 3 units of ACD blood were used: in children, a smaller volume prime was used. There was always an approximate one-to-one ratio of blood to nonblood constituents in the prime. The standard prime used for adults is shown in Table 1. Calcium as a 10% solution of calcium chloride was added to the pumpoxygenator prime after the prime had been heparinized. In some patients, magnesium as a 10% solution of magnesium sulfate was also added. The prime was internally circulated to ensure thorough mixing prior to the institution of cardiopulmonary bypass. The patients were divided into three groups according to the dosages of calcium chloride and magnesium sulfate added (Table 2). Heparinized blood samples were obtained from each patient just prior to the institution of cardiopulmonary bypass. Samples were also obtained from the pumpoxygenator prime prior to and following addition of the calcium and magnesium solutions. Additional samples were taken from each patient at 5, 15, 30, 60, and 120 minutes following the initiation of bypass. When cardiopulmonary bypass was for a shorter period than two hours, the later samples TABLE 2. CALCIUM AND MAGNESIUM ADDED TO PRIME Calcium Magnesium Chloride" Sulfatea No. of Patient Group (ml.) (ml.) Patients I 6 None 11 I I "Volume of 10% solution per unit of ACD presented blood. *Med-Science Electronic Go.. St. Louis, Mo. tbentley Laboratories, Santa Ana, Calif. 372 THE ANNALS OF THORACIC SURGERY

3 Eflect of ACD Blood on Plasma Calcium and Magnesium FIG. 1. Top is a proportional- [Ca+ +I ity formula that can be derived - from the dissociation equilibria [total calcium] of calcium and magnesium citrate and calcium and magne- [Mg+ +I sium hoteinate [61. Bottom is -? an hpproximation formula Km which assumes equal afinity [Mg cit.] + [Mg+ +I + -[Mg prot.] (equal dissociation constants) of K, phma proteins for ionized calcium and ionized magnesium. [Ca+ +I [Mg+ +I s5 [total calcium] [total magnesium] were taken from the patient at the appropriate times, although bypass had been discontinued. Not all scheduled samples were obtained in each patient. Based on clinical judgment, additional aliquots of calcium chloride solution were administered at the end of cardiopulmonary bypass in an effort to increase the contractility of the heart in some instances. Plasma levels of total calcium and total magnesium were measured using an atomic absorption spectrophotometer.' The plasma calcium ion activity was measured directly with a calcium ion electrode.? The plasma acid-base balance was restored by bubbling a 95% oxygen-5% carbon dioxide mixture through the specimen immediately prior to measuring the ionized calcium. All measurements were at room temperature. An expanded-scale ph meter was utilized to monitor the calcium ion electrode potential. The electrode system was calibrated using known calcium ion standards furnished by the electrode manufacturer, and a point check was made using one of the standards before each work session. Measurement of simultaneous total calcium, total magnesium, and calcium ion concentrations permitted calculation of the plasma ionized magnesium value using a simple proportionality formula (Fig. 1) [61. The ranges of normal plasma values of total calcium and total magnesium were assumed to be the same as those reported by others, and the course of the observed values was assessed relative to these normal ranges. The range of normal plasma values of ionized calcium was determined by measuring the plasma calcium ion activity in a group of apparently normal individuals. Statistical analysis of these data was performed, and the distribution within the mean *Z (T was arbitrarily accepted as the normal range. The normal range (mean A2 (T) for the calculated values of plasma ionized magnesium was determined similarly. The courses of the ionized calcium and magnesium found in the present study were assessed relative to these normal ranges of values. For the purposes of analysis, the plasma total and ionized calcium data *Model 303, Perkin-Elmer Corp., Norwalk, Conn.?Model 99-20, Orion Research, Inc., Cambridge, Mass.

4 KILLEN ET AL. of Groups I and I1 were combined. Similarly, the magnesium data of Groups I1 and I11 were also combined. Results A total plasma calcium range of 4.25 to 5.5 meq. per liter and a total plasma magnesium range of 1.4 to 2.2 meq./l. were accepted as the normal [5, 81. The ionized plasma calcium was measured directly in 10 normal individuals, and a normal range (mean -+2 0) of 1.66 to 2.4 meq./l. was found. The normal range of ionized plasma magnesium was calculated in these 10 individuals as described and was found to be 0.6 to 0.9 meq./l. The normal ranges are shaded in Figures 2 through 9. The course of the total plasma calcium in Group I and I1 patients, in whom the pump-oxygenator prime was reconstituted with 6 ml. of 10% calcium chloride per unit of ACD blood, is shown in Figure 2. The mean value of the prime prior to the addition of calcium chloride was only 1.5 meq./l. Following the addition of calcium chloride and internal circulation of the prime, the mean value was 10 meq./l. With the initiation of cardiopulmonary bypass the total calcium level fell toward normal, and after 15 minutes the mean value was within the normal range. The ionized calcium was severely depressed in the prime prior to the addition of calcium chloride, with a mean value of only 0.09 meq./l. (Fig. 3). After the addition of calcium chloride the mean ionized calcium value of the prime was 1.15 meq./l. The mean ionized calcium rose to a normal range during the first 30 minutes of bypass. However, it is evident that only patients receiving an additional amount of calcium chloride at the termination of bypass were in a highnormal range at two hours following initiation of bypass (cf. Fig. 3). "1 TOTAL CALCIUM t 0' PATIENT PRIME PRIME '5.I I20 PWS BEClN (:.Fg:) CDCl* BY-P*SS TIME (MINJ FIG. 2. Course of total plasma calcium in Group Z and ZZ patients, who had primes reconstituted with 10% calcium chloride, 6 ml. per unit ACD blood. The circled points Jignify patients receiving an additional amount of calcium chloride as they were removed from cardiopulmonary bypass. The shaded band is the normal range. 3'74 THE ANNALS OF THORACIC SURGERY

5 Effect of ACD Blood on Plasma Calcium and Magnesium 3' m a CO++ 2 i i' : i 0.5- The course of the total plasma calcium in Group I11 patients, in whom the pump-oxygenator prime was reconstituted with 8 ml. of 10% calcium chloride per unit of ACD blood, is shown in Figure 4. The total calcium in the prime before calcium chloride was added was 1.5 meq./l. and after the addition of calcium chloride, 12.3 meq./l. The mean total calcium fell to a normal range after 30 minutes of cardiopulmonary bypass. The ionized plasma calcium was 0.08 meq./l. in the prime before the addition of calcium chloride and rose to 1.6 meq./l. after the addition of calcium chloride (Fig. 5). In most instances the ionized calcium remained in the normal range CALCl U M 8 VOL. 13, NO. 4, APRIL,

6 KILLEN ET AL. '"1 2.5 CO" (meq 1 L) ls0l. 0 I 1 PATIENT PRIME PRIME $0 9'0 li0 (&:\:) PLUS cocii BEGIN BY-PASS TIME (MIN.1 FIG. 5. Course of ionized plasma calcium in Group IZZ patients, who underwent bypass with prime reconstituted with 10% calcium chloride, 8 ml. per unit ACD blood. The circled points signify the patient receiving an additional amount of calcium chloride as he was removed from cardiopulmonary bypass. The shaded band is the normal range. throughout the period of observation. The patient who received an additional infusion of calcium chloride at the end of cardiopulmonary bypass exhibited a supernormal ionized calcium level (see Fig. 5). The course of the total plasma magnesium in Group I patients, in whom no magnesium sulfate was added to the prime, is shown in Figure 6. The total magnesium was in a relatively normal range throughout the period of observation. However, the ionized plasma magnesium of the prime was severely depressed, with a value of 0.07 meq./l. before the addition of calcium chloride (Fig. 7). There was a rise of the ionized magnesium to TOTAL MAGNESIUM heqll) 3 2 I.. 0 PATkNT PRiME PRIME? I20 (&E-;Ofit) PLUSCoCIa BEGIN BY-PASS TIME IMIN.1 FIG. 6. Course of total plasma magnesium in Group I patients, who underwent bypass with prime reconstituted with no magnesium sulfate. The shaded band is the normal range. 376 THE ANNALS OF THORACIC SURGERY

7 Eflect of ACD Blood on Plasma Calcium and Magnesium 1.0 I'I/ 0.21! t I T. 0'.: PATIENT PRIME PRIME f PLUS BEGIN (::;:g) COCll BY-PISS TIME (MIN.) FIG. 7. Course of ionized plasma magnesium in Group I patients, who underwent bypass with prime reconstituted with no magnesium sulfate. The shaded band is the normal range. meq./l. after the addition of calcium chloride. The ionized plasma magnesium level rose during cardiopulmonary bypass with return to a normal range only after approximately one hour. The course of the total plasma magnesium in Group I1 and I11 patients, in whom 10% magnesium sulfate in an amount of 3 ml. per unit of ACD blood was added to the prime, is shown in Figure 8. The total magnesium in the prime rose from 1.2 meq./l. to 4.1 meq./l. with the addition of magnesium sulfate. The total magnesium rapidly fell toward the normal range during cardiopulmonary bypass. The ionized magnesium of the prime 5 I141. TOTAL MAGNESIUM ImEqIL) 4 2 I OJ (gf&!:) ~ 0 ~ 0, p*iiew PRiME PRIME ' PLUS BEGIN w.p*u TIME (MIN.) FIG. 8. Course of total plasma magnesium in Group ZZ and I11 patients, who underwent bypass with prime reconstituted with 10% magnesium sulfate, 3 ml. per unit ACD blood. The shaded band is the normal range.

8 KILLEN ET AL. 1 I.o 0.21 i. I OJ d, PATIENT PRIME PRIME PLUS BEGIN (E-\t!i) MpSO. BY-PASS (MIN.) FIG. 9. Course of ionized plasma magnesium in Group II and III patients, who underwent bypass with prime reconstituted with 10% magnesium sulfate, 3 ml. per unit ACD blood. The shaded band is the normal range. rose from 0.08 meq./l. to 0.54 meq./l. with the addition of magnesium sulfate to the prime (Fig. 9). The ionized magnesium remained in a relatively normal range throughout the period of observation (see Fig. 9). Comment Under most circumstances, transfusion of ACD preserved blood does not severely depress the plasma ionized calcium [I, 71. However, there are situations in which massive infusion of ACD preserved blood can significantly lower the plasma ionized calcium [3, 10, 111. Rapid massive transfusion in the presence of shock or hypothermia or both may depress the ionized calcium significantly. Another such situation exists during cardiopulmonary bypass when ACD preserved blood is used to prime the pump-oxygenator. It has been demonstrated by others that the addition of 6 ml. of 10% calcium chloride per unit of ACD blood in the pump-oxygenator prime is appropriate to reverse the calcium binding effect of the ACD solution [6, 101. This amount of calcium chloride should be optimal in restoring the normal ionized calcium level; however, in the present study the ionized calcium of the prime was not returned to normal levels. This is perhaps the result of the hemodilution effect of the nonblood constituents of the prime (see Table 1 and Fig. 3). When a larger dose of 10% calcium chloride was given (8 ml. per unit ACD blood), the ionized calcium rose to a normal level and there was no need for the additional administration of calcium during and immediately following cardiopulmonary bypass (see Fig. 5). $ The magnesium binding effect of ACD solution has been recognized for decades; however, no detrimental effect has been observed after the infusion of ACD preserved blood. Chronic magnesium depletion can result in a 378 THE ANNALS OF THORACIC SURGERY

9 Eflect of ACD Blood on Plasma Calcium and Magnesium syndrome of hypomagnesemia causing neurological symptoms, cardiac arrhythmias, and other problems [Z, 41. It is not known whether such a syndrome may result from acute lowering of the plasma ionized magnesium. It is well documented in the present study that extreme lowering of the ionized magnesium occurs when ACD blood that is reconstituted with calcium chloride is administered (see Fig. 7). The addition of an appropriate amount of magnesium sulfate solution to the prime returns the ionized magnesium to normal. Although there is no proof of the hypothesis that the hypomagnesemia experienced during cardiopulmonary bypass may be detrimental to the patient, it is possible that some of the complications (neurological signs, arrhythmias) exhibited immediately following cardiopulmonary bypass could be related to this unphysiological consequence of the use of ACD blood pump-oxygenator prime. Others have demonstrated a syndrome of magnesium depletion following cardiopulmonary bypass [9]. However, this was documented later in the postoperative course than the period of observation in the present study. The use of ACD preserved blood in the prime cannot be incriminated for this observed late magnesium depletion. There are special situations in which the heart is unusually sensitive to lowering of the plasma ionized calcium. The heart denervated by either transplantation or pharmacological blockade is extremely sensitive to lowered ionized calcium [3, 113. Slow infusion of ACD preserved blood to animals with autotransplanted hearts has been observed to result in death due to the negative inotropic effect of the lowered ionized calcium. Animals (and probably human beings) on long-term pharmacological regimens which interfere with the normal mechanisms of production, storage, and release of myocardial catecholamines may exhibit extreme sensitivity to lowering of the plasma ionized calcium. This may also be true in the chronic failing heart, in which the endogenous catecholamine supplies have been found to be markedly depressed. In recent years, improvements in pump-oxygenators and refinements of cardiopulmonary bypass techniques have made it feasible to decrease the priming volume of the pump-oxygenator. As the priming volume is decreased, the need for the use of ACD preserved blood is lessened and the changes of plasma calcium and magnesium as observed in the current study would be expected to be of less concern. Even so, the data presented are helpful in more clearly understanding the physiological alterations induced by cardiopulmonary bypass when ACD preserved blood is used in the prime. References 1. Bunker, J. P., Bendixen, H. H., and Murphy, A. J. Hemodynamic effects of intravenously administered sodium citrate. N. Engl. J. Med. 266:372, Caddell, J. L. Magnesium in the therapy of protein-calorie malnutrition of childhood. Pediatrics 66:392, Corbascio, A. N., and Smith, N. T. Hemodynamic effects of experimental hypercitremia. Anesthesiology 28:510, 1967.

10 KILLEN ET AL. 4. Gerst, P. H., Porter, M. R., and Fishman, R. A. Symptomatic magnesium deficiency in surgical patients. Ann. Surg. 159:402, HofEman, W. S. The Biochemistry of Clinical Medicine, 3d ed. Chicago: Year Book, P Killen, D. A., Grogan, E. L., 11, Gower, R. E., and Collins, H. A. Response of canine plasma ionized calcium and magnesium to the rapid infusion of ACD solution. Surgery 70:736, Ludbrook, J., and Wynn, V. Citrate intoxication: A clinical and experimental study. Br. Med. J. 2:523, Randall, H. T. Fluid and Electrolyte Therapy. In American College of Surgeons, Manual of Preoperative and Postoperative Care. Philadelphia: Saunders, Scheinman, M. M., Sullivan, R. W., and Hyatt, K. H. Magnesium metabolism in patients undergoing cardiopulmonary bypass. Circulation 39 (Suppl. I):235, Sessler, A. D., Taswell, H. F., Moffitt, E. A., and Kirklin, J. W. Heparinized versus acid-citrate-dextrose blood for cardiopulmonary bypass. Mayo Clin. Proc. 40:859, Smith, N. T., and Hurley, E. J. Citrate infusion in dogs following cardiac autotransplantation: Studies on cardiovascular effects. Arch. Surg. 98:44, THE ANNALS OF THORACIC SURGERY