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Hyperkalemia after irradiation of packed red blood cells: Possible effects with intravascular fetal transfusion
Volume 163 Number 2
imaging of the human fetus in utero at 0.5 T. Br 1 Radiol 1990 [In press). 13. Ordidge R, Howseman AM, Coxon R, et al. Snap-shot imaging at 0.5 T using echo-planar techniques. Magn Reson Med 1989;10;227-40. l4. Johnson IR, Symonds EM, Kean DM, et al. Imaging the pregnant human uterus with nuclear magnetic resonance. AMJ OBSTET GYNECOL 1984;148:1136-9. 15. Powell MC, Worthington BS, Buckley 1M, Symonds EM. Magnetic resonance imaging in obstetrics. Br J Obstet GynaecoI1988;95:38-46.
Human fetal echo-planar imaging in utero
16. O'Callaghan C, Small P, Chapman B, et al. Determination of individual and total lung volumes using NMR echoplanar imaging. Ann Radiol 1987;30:470-2. 17. Frahm J, Haase A, Matthaei D. Rapid NMR imaging of dynamic processes using the FLASH technique. Magn Reson Med 1986;3:321-7. 18. Haase A, Matthaei D, Norris D. Snap-shot FLASH imaging. In: Proceedings of the eighth annual meeting of the Society of Magnetic Resonance in Medicine, Amsterdam. Berkeley, California: Society of Magnetic Resonance in Medicine, 1989:364.
Hyperkalemia after irradiation of packed red blood cells: Possible effects with intravascular fetal transfusion James A. Thorp, MD: Fred V. Plapp, MD, PhD,b Gary R. Cohen, MD: John D. Yeast, MD: Richard T. O'KelI, MD,b and Stephanie Stephenson, RNa
Kansas City, Missouri Plasma potassium, calcium, and albumin concentrations in irradiated blood, and in fetal blood before and after transfusion, were measured. Dangerously high plasma potassium levels were observed in some units of irradiated packed red blood cells (range, 13.9 to 66.5 mEq/L; mean, 44.7 mEq/L) and could be one possible explanation for the high incidence of fetal arrhythmia associated with fetal intravascular transfusion. There are many factors operative in the preparation of irradiated packed red blood cells that may predispose to high potassium levels: the age of the red blood cells, the number of procedures used to concentrate the blood, the duration of time elapsed from concentration, the duration of time elapsed from irradiation, and the hematocrit. Use of fresh blood, avoidance of multiple packing procedures, limiting the hematocrit in the donor unit to s;80%, and minimizing the time between concentration, irradiation and transfusion may minimize the potassium levels, and therefore making an additional washing procedure unnecessary. (AM J OBSTET GYNECOL 1990;163:607-9.)
Key words: Hyperkalemia, fetal intravascular transfusion, irradiation of packed red blood cells Irradiation of blood before transfusion of the fetus and neonate is important because it effectively prevents graft versus host disease. Recent reports suggest that irradiation results in hyperkalemia in the donor plasma. 1·4 Ramirez et al. 1 found plasma potassium levels to be 53 mEq/L after irradiation and 4 days of storage, compared with a control value of 17 mEq/L. Two other studies 2 . , reported similar elevations of potassium after irradiation and found that potassium levels could be significantly reduced by manual washing procedures. These elevated potassium levels may cause dangerously
From St. Luke's Perinatal Center" and the Department of Laboratory Medicine,' St. Luke's Hospital. Received for publication December 27, 1989; revised March 13, 1990; accepted April 11, 1990. Reprint requests: James A. Thorp, MD, St. Luke's Perinatal Center, St. Luke's Hospital, Kansas City, MO 64111. 6/1121549
high plasma concentrations in the fetus or neonate." 4 A 24-week fetus weighing 600 gm has a circulating fetoplacental blood volume of approximately 96 m\. Blood transfusions in excess of 50 ml/kg fetal weight are being performed by us and others. If such a fetus (hematocrit == 20% and plasma potassium == 3.5 mEq/L) receives 30 ml of transfused blood (hematocrit == 80% and plasma potassium == 50 mEq/L), the potassium bolus into the central vein exceeds the total plasma potassium of the entire fetoplacental unit. This massive potassium bolus injected into a central vein of an already compromised fetus may account for the high frequency of fetal arrhythmia associated with intravascular fetal transfusions! Fetal arrhythmias associated with intravascular transfusion may be letha\.' Other factors including the temperature of transfused blood, volume transfused, citrate concentrations, and calcium levels may also predispose to fetal arrhythmia during intravascular transfusion.
607
608 Thorp et al.
August 1990 Am J Obstet Gynecol
Table I. Potassium, calcium, and albumin in donor blood and in fetal blood before and after transfusion Potassium in donated blood (mEq/L) Pretransfusion fetal potassium (mEq/L) Posttransfusion fetal potassium (mEq/L) Calcium in donated blood (mEq/L) Pretransfusion fetal calcium (mEq/L) Posttransfusion fetal calcium (mEq/L) Albumin in donated blood (gm/dl) Pretransfusion fetal albumin (gm/ dl) Posttransfusion fetal albumin (gm/ dl)
Mean ± SD
N
44.7 3.3 4.1 8.2 8.9 9.1 3.0 2.3 2.0
8 4 6 5 3 3 5
± 17.9 ± 0.3 ± 0.7* ± 0.8 ± 0.1 ± 0.3 ± 0.2 ± 0.2 ± 0.8
3
3
*Significantly increased from pretransfusion value, p < 0.05 by t test.
Table II. Factors predicting plasma potassium levels in units of irradiated packed red blood cells (n = 8) Age of unit before radiation (hr) Time between radiation and transfusion (hr) Hematocrit of unit (%)
Mean ± SD
t Value
p Value*
93.0 ± 27.0
0.50
0.64
12.6 ± 6.7
2.50
0.06
77.0 ± 8.8
3.00
0.04
*The p value is determined by multivariate regression analysis with plasma potassium in the irradiated packed red blood cells used as the dependent variable and each of the three factors used as the independent variables.
mEq/L after transfusion, without resultant fetal arrhythmia. In another fetus we transfused 54 ml of blood with a serum potassium of66.5 mEq/L to a 1550 gm fetus without evidence of arrhythmia. The equivalent volume of hyperkalemic solution injected rapidly into the central vein of an adult would be very dangerous. We have seen four transient fetal arrhythmias during or after 42 intravascular transfusions. Since we began monitoring fetal potassium levels, only one of seven transfusions was associated with a fetal arrhythmia. This one instance of transient bradycardia occurred immediately after transfusion of 75 ml of donor blood with a plasma potassium of 58 mEq/L to an 800 gm fetus. Results
Table III. Effect of a single concentrating procedure versus two concentrating procedures on plasma potassium of fresh blood No. of procedures
1
2
9
4
Hematocrit (%)
Potassium (mEq/L)
74.7 91.3*
4.0 5.5*
*These values are significantly increased when compared with the values obtained after only one concentrating procedure (p < 0.001 by t test).
Methods
Recently we measured potassium, calcium, and albumin concentrations in irradiated blood and in fetal blood before and after transfusion (Table I). Potassium levels in units of irradiated packed red blood cells ranged from 13.9 to 66.5 mEq/L (mean, 44.7 mEq/L; SD = 17.9 mEq/L; n = 8). Large boluses of intravenous potassium in the fetus do not appear to cause a sustained increase in serum potassium, presumably because of tissue equilibration, renal excretion, and placental transfer. We have observed a fetal potassium increase from 3.2 mEq/L before transfusion to 5.3
Multivariate regression analysis was performed to determine which of the following factors (age of the unit of blood before irradiation, hematocrit of the unit of packed red blood cells, and the time between irradiation of blood and transfusion) correlated best with the plasma potassium of the donor blood. Both the hematocrit of the unit of packed red blood cells and the duration of time between irradiation and transfusion correlated best (Table II). The three highest plasma potassium levels (66.5, 65.3, and 58.0 mEq/L) were associated with the three highest hematocrits (86%, 84%, and 84%, respectively). The lowest plasma potassium in the donor blood (13.9 mEq/L) was observed when the duration of time from irradiation to transfusion was only 3 hours. However, in one unit of blood we observed only a minimal rise in potassium, from 36 mEq/L 2 hours after irradiation to only 44.3 mEq/L 24 hours after irradiation. Therefore there appears to be other factors involved with the rise in potassium levels. Because the variance in the plasma potassium of the donated blood could not be explained entirely by the hematocrit of the donor blood or the time elapsed after irradiation, we sought other explanations. We found that the regional blood center had concentrated some units of blood a second time to achieve a higher he-
Volume 163 Number 2
matocrit. To further clarify this issue we studied nine additional units of fresh blood (=0;5 days of age), five of which were centrifuged only once, and four of which were centrifuged twice and had plasma removed after each centrifugation (Table III). The hematocrit and potassium levels were significantly elevated (p < 0.001) after the second centrifugation. This probably occurred because the highly concentrated units had additional plasma removed. There was less plasma available for distribution of the potassium leaking out of the irradiated red blood cells. In addition, the removal of more anticoagulant-preservative solution resulted in less adenosine and glucose to support sodiumpotassium adenosine triphosphatase. Inhibition of this enzyme would further accentuate potassium leakage.
Comment There appear to be many factors operative in the preparation of irradiated packed red blood cells that may predispose to high potassium levels: the age of the red blood cells, the number of procedures used to concentrate the blood, the duration of time elapsed from concentration, the duration of time elapsed from irradiation, and the hematocrit. We conclude that each of these factors may contribute to cause a slow potas-
Hyperkalemia after red cell irradiation
609
sium leak in the red blood cell membrane, therefore causing a rising plasma potassium. Manual washing of irradiated packed red blood cells with saline solution significantly reduces the donor plasma potassium. This procedure is technically cumbersome and adds further time delay and expense. Use of fresh blood, avoidance of multiple packing procedures, and minimizing the time between concentration, irradiation, and transfusion may keep the potassium levels low, therefore making an additional washing procedure unnecessary. Further study is necessary to determine how much potassium can be safely administered during intravascular transfusion, and to determine if washing techniques are necessary. REFERENCES 1. Ramirez AM, Woodfield DG, Scott R, McLachlan J. High potassium levels in stored irradiated blood [Letter]. Transfusion 1987;27 :444-5. 2. Rivet C, Baxter A, Rock G. Potassium levels in irradiated blood. Transfusion 1989;29:185. 3. Galligan BR, Cairns R, Schifano JV, Selbing A, Bernvil SS. Preparation of packed red cells suitable for intravascular transfusion in utero. Transfusion 1989;29:179-81. 4. Ferguson DJ. Potassium levels in irradiated blood [Letter and response]. Transfusion 1989;29:749-50.
imaging of the human fetus in utero at 0.5 T. Br 1 Radiol 1990 [In press). 13. Ordidge R, Howseman AM, Coxon R, et al. Snap-shot imaging at 0.5 T using echo-planar techniques. Magn Reson Med 1989;10;227-40. l4. Johnson IR, Symonds EM, Kean DM, et al. Imaging the pregnant human uterus with nuclear magnetic resonance. AMJ OBSTET GYNECOL 1984;148:1136-9. 15. Powell MC, Worthington BS, Buckley 1M, Symonds EM. Magnetic resonance imaging in obstetrics. Br J Obstet GynaecoI1988;95:38-46.
Human fetal echo-planar imaging in utero
16. O'Callaghan C, Small P, Chapman B, et al. Determination of individual and total lung volumes using NMR echoplanar imaging. Ann Radiol 1987;30:470-2. 17. Frahm J, Haase A, Matthaei D. Rapid NMR imaging of dynamic processes using the FLASH technique. Magn Reson Med 1986;3:321-7. 18. Haase A, Matthaei D, Norris D. Snap-shot FLASH imaging. In: Proceedings of the eighth annual meeting of the Society of Magnetic Resonance in Medicine, Amsterdam. Berkeley, California: Society of Magnetic Resonance in Medicine, 1989:364.
Hyperkalemia after irradiation of packed red blood cells: Possible effects with intravascular fetal transfusion James A. Thorp, MD: Fred V. Plapp, MD, PhD,b Gary R. Cohen, MD: John D. Yeast, MD: Richard T. O'KelI, MD,b and Stephanie Stephenson, RNa
Kansas City, Missouri Plasma potassium, calcium, and albumin concentrations in irradiated blood, and in fetal blood before and after transfusion, were measured. Dangerously high plasma potassium levels were observed in some units of irradiated packed red blood cells (range, 13.9 to 66.5 mEq/L; mean, 44.7 mEq/L) and could be one possible explanation for the high incidence of fetal arrhythmia associated with fetal intravascular transfusion. There are many factors operative in the preparation of irradiated packed red blood cells that may predispose to high potassium levels: the age of the red blood cells, the number of procedures used to concentrate the blood, the duration of time elapsed from concentration, the duration of time elapsed from irradiation, and the hematocrit. Use of fresh blood, avoidance of multiple packing procedures, limiting the hematocrit in the donor unit to s;80%, and minimizing the time between concentration, irradiation and transfusion may minimize the potassium levels, and therefore making an additional washing procedure unnecessary. (AM J OBSTET GYNECOL 1990;163:607-9.)
Key words: Hyperkalemia, fetal intravascular transfusion, irradiation of packed red blood cells Irradiation of blood before transfusion of the fetus and neonate is important because it effectively prevents graft versus host disease. Recent reports suggest that irradiation results in hyperkalemia in the donor plasma. 1·4 Ramirez et al. 1 found plasma potassium levels to be 53 mEq/L after irradiation and 4 days of storage, compared with a control value of 17 mEq/L. Two other studies 2 . , reported similar elevations of potassium after irradiation and found that potassium levels could be significantly reduced by manual washing procedures. These elevated potassium levels may cause dangerously
From St. Luke's Perinatal Center" and the Department of Laboratory Medicine,' St. Luke's Hospital. Received for publication December 27, 1989; revised March 13, 1990; accepted April 11, 1990. Reprint requests: James A. Thorp, MD, St. Luke's Perinatal Center, St. Luke's Hospital, Kansas City, MO 64111. 6/1121549
high plasma concentrations in the fetus or neonate." 4 A 24-week fetus weighing 600 gm has a circulating fetoplacental blood volume of approximately 96 m\. Blood transfusions in excess of 50 ml/kg fetal weight are being performed by us and others. If such a fetus (hematocrit == 20% and plasma potassium == 3.5 mEq/L) receives 30 ml of transfused blood (hematocrit == 80% and plasma potassium == 50 mEq/L), the potassium bolus into the central vein exceeds the total plasma potassium of the entire fetoplacental unit. This massive potassium bolus injected into a central vein of an already compromised fetus may account for the high frequency of fetal arrhythmia associated with intravascular fetal transfusions! Fetal arrhythmias associated with intravascular transfusion may be letha\.' Other factors including the temperature of transfused blood, volume transfused, citrate concentrations, and calcium levels may also predispose to fetal arrhythmia during intravascular transfusion.
607
608 Thorp et al.
August 1990 Am J Obstet Gynecol
Table I. Potassium, calcium, and albumin in donor blood and in fetal blood before and after transfusion Potassium in donated blood (mEq/L) Pretransfusion fetal potassium (mEq/L) Posttransfusion fetal potassium (mEq/L) Calcium in donated blood (mEq/L) Pretransfusion fetal calcium (mEq/L) Posttransfusion fetal calcium (mEq/L) Albumin in donated blood (gm/dl) Pretransfusion fetal albumin (gm/ dl) Posttransfusion fetal albumin (gm/ dl)
Mean ± SD
N
44.7 3.3 4.1 8.2 8.9 9.1 3.0 2.3 2.0
8 4 6 5 3 3 5
± 17.9 ± 0.3 ± 0.7* ± 0.8 ± 0.1 ± 0.3 ± 0.2 ± 0.2 ± 0.8
3
3
*Significantly increased from pretransfusion value, p < 0.05 by t test.
Table II. Factors predicting plasma potassium levels in units of irradiated packed red blood cells (n = 8) Age of unit before radiation (hr) Time between radiation and transfusion (hr) Hematocrit of unit (%)
Mean ± SD
t Value
p Value*
93.0 ± 27.0
0.50
0.64
12.6 ± 6.7
2.50
0.06
77.0 ± 8.8
3.00
0.04
*The p value is determined by multivariate regression analysis with plasma potassium in the irradiated packed red blood cells used as the dependent variable and each of the three factors used as the independent variables.
mEq/L after transfusion, without resultant fetal arrhythmia. In another fetus we transfused 54 ml of blood with a serum potassium of66.5 mEq/L to a 1550 gm fetus without evidence of arrhythmia. The equivalent volume of hyperkalemic solution injected rapidly into the central vein of an adult would be very dangerous. We have seen four transient fetal arrhythmias during or after 42 intravascular transfusions. Since we began monitoring fetal potassium levels, only one of seven transfusions was associated with a fetal arrhythmia. This one instance of transient bradycardia occurred immediately after transfusion of 75 ml of donor blood with a plasma potassium of 58 mEq/L to an 800 gm fetus. Results
Table III. Effect of a single concentrating procedure versus two concentrating procedures on plasma potassium of fresh blood No. of procedures
1
2
9
4
Hematocrit (%)
Potassium (mEq/L)
74.7 91.3*
4.0 5.5*
*These values are significantly increased when compared with the values obtained after only one concentrating procedure (p < 0.001 by t test).
Methods
Recently we measured potassium, calcium, and albumin concentrations in irradiated blood and in fetal blood before and after transfusion (Table I). Potassium levels in units of irradiated packed red blood cells ranged from 13.9 to 66.5 mEq/L (mean, 44.7 mEq/L; SD = 17.9 mEq/L; n = 8). Large boluses of intravenous potassium in the fetus do not appear to cause a sustained increase in serum potassium, presumably because of tissue equilibration, renal excretion, and placental transfer. We have observed a fetal potassium increase from 3.2 mEq/L before transfusion to 5.3
Multivariate regression analysis was performed to determine which of the following factors (age of the unit of blood before irradiation, hematocrit of the unit of packed red blood cells, and the time between irradiation of blood and transfusion) correlated best with the plasma potassium of the donor blood. Both the hematocrit of the unit of packed red blood cells and the duration of time between irradiation and transfusion correlated best (Table II). The three highest plasma potassium levels (66.5, 65.3, and 58.0 mEq/L) were associated with the three highest hematocrits (86%, 84%, and 84%, respectively). The lowest plasma potassium in the donor blood (13.9 mEq/L) was observed when the duration of time from irradiation to transfusion was only 3 hours. However, in one unit of blood we observed only a minimal rise in potassium, from 36 mEq/L 2 hours after irradiation to only 44.3 mEq/L 24 hours after irradiation. Therefore there appears to be other factors involved with the rise in potassium levels. Because the variance in the plasma potassium of the donated blood could not be explained entirely by the hematocrit of the donor blood or the time elapsed after irradiation, we sought other explanations. We found that the regional blood center had concentrated some units of blood a second time to achieve a higher he-
Volume 163 Number 2
matocrit. To further clarify this issue we studied nine additional units of fresh blood (=0;5 days of age), five of which were centrifuged only once, and four of which were centrifuged twice and had plasma removed after each centrifugation (Table III). The hematocrit and potassium levels were significantly elevated (p < 0.001) after the second centrifugation. This probably occurred because the highly concentrated units had additional plasma removed. There was less plasma available for distribution of the potassium leaking out of the irradiated red blood cells. In addition, the removal of more anticoagulant-preservative solution resulted in less adenosine and glucose to support sodiumpotassium adenosine triphosphatase. Inhibition of this enzyme would further accentuate potassium leakage.
Comment There appear to be many factors operative in the preparation of irradiated packed red blood cells that may predispose to high potassium levels: the age of the red blood cells, the number of procedures used to concentrate the blood, the duration of time elapsed from concentration, the duration of time elapsed from irradiation, and the hematocrit. We conclude that each of these factors may contribute to cause a slow potas-
Hyperkalemia after red cell irradiation
609
sium leak in the red blood cell membrane, therefore causing a rising plasma potassium. Manual washing of irradiated packed red blood cells with saline solution significantly reduces the donor plasma potassium. This procedure is technically cumbersome and adds further time delay and expense. Use of fresh blood, avoidance of multiple packing procedures, and minimizing the time between concentration, irradiation, and transfusion may keep the potassium levels low, therefore making an additional washing procedure unnecessary. Further study is necessary to determine how much potassium can be safely administered during intravascular transfusion, and to determine if washing techniques are necessary. REFERENCES 1. Ramirez AM, Woodfield DG, Scott R, McLachlan J. High potassium levels in stored irradiated blood [Letter]. Transfusion 1987;27 :444-5. 2. Rivet C, Baxter A, Rock G. Potassium levels in irradiated blood. Transfusion 1989;29:185. 3. Galligan BR, Cairns R, Schifano JV, Selbing A, Bernvil SS. Preparation of packed red cells suitable for intravascular transfusion in utero. Transfusion 1989;29:179-81. 4. Ferguson DJ. Potassium levels in irradiated blood [Letter and response]. Transfusion 1989;29:749-50.