Changes in potassium and sodium concentrations in stored blood

Changes in potassium and sodium concentrations in stored blood

Clement Opoku-Okrah¹, Benjamin Kojo Safo Acquah¹, Elliot Eli Dogbe^2,&

¹Department of Medical Laboratory Technology, Kwame Nkrumah University of Science and Technology, Kumasi, Ghana, ²Transfusion Medicine Unit, Komfo Anokye Teaching Hospital, Kumasi, Ghana

^&Corresponding author
Elliot Eli Dogbe, Transfusion Medicine Unit, Komfo Anokye Teaching Hospital, Kumasi – Ghana

Electrolyte disturbances can be associated with a number of occurrences including drug usage [1] but the kidney is expected to manage it. Hypokalaemia and hyperkalaemia has been seen as problem for some hospitalized patients [2] with hyperkalaemia being implicated for complications of massive blood transfusion [3-5]. It has been observed that following blood transfusion of stored blood, complications such as hyperkalaemia, hyponatraemia and citrate toxicity among other conditions do occur [6]. During blood storage, there is a slow but constant leakage of potassium from the cells into the surrounding plasma along a concentration gradient as a result of sodium potassium ATPase pump failure. The plasma level of potassium may increase by 0.5-1.0mmol/L per day of refrigerator storage [7]. There is a notion that the total amount of extracellular potassium in a unit of blood stored for 35days falls within 7mmol/L to 25mmol/L [8]. The resultant impact of transfusion of stored blood on the potassium and acid-base balance on the recipient is very complex. It is however, largely dependent on the rate of transfusion, volume of blood transfused, the rate of citrate metabolism and the changing state of the peripheral perfusion of the patient/recipient [3,9]. Failure to establish the apparent electrolyte changes has been found to be fatal in some instances [10].

Sodium is the major electrolyte in the extracellular fluid (ECF) with about 98% of its totality being in the ECF and only 2% being in the intracellular fluid (ICF) with a reference range of 135-145mEq/L. Sodium levels below135mEq/L results in a condition termed hyponatraemia caused by low levels of sodium or excess water in relation to the amount of sodium with post-operative patients commonly experiencing it [11]. A drop in sodium concentration causes cellular oedema which affects the central nervous system and leads to depression and cerebral oedema [12]. Sodium levels above 145mEq/L results in hypernatremia, a condition that is generally associated with a hyperosmolar state where a fluid volume exists. The increase in extracellular sodium causes intracellular to shift out of the cells into extracellular spaces, which results in cellular dehydration. Also, cardiac output is reduced due to decreased myocardial contractility leading to heart failure [13]. Potassium is the major element in the intracellular fluid (ICF) with about 98% of its totality being the ICF leaving 2% in the ECF with a reference range of 3.5-5.0mEq/L; thus plasma potassium being of a small fraction of, and an accurate reflection of whole body potassium [14,15]. Potassium storage and its distribution within the body has been noted to be regulated by very important hormones with its normal transcellular distribution of high intracellular to extracellular ratio being maintained by three hormonal signals, insulin, aldosterone and β-adrenergic catecholamines [16]; buffering of ECF potassium through uptake of potassium by cell is greatly impaired by the absence of aldosterone, insulin or catecholamines [17]. Potassium uptake by all cells is through the Na-K ATPase pump; being one of the most permeable ions across cell membranes and makes use of the potassium channels to exit cells: in some cells via K-H exchange or via K-Cl co-transport) [18]. Potassium remains the major ion determinant of the resting membrane electrical potential, which limits and opposes potassium efflux giving rise to changes in ECF potassium concentrations that have marked effects on cell excitability within the heart, brain, nerve and muscles [19]. ICF potassium leakage to the ECF increases when osmolarity increases, as in diabetes mellitus and in metabolic acidosis during which it is exchanged for ECF protons (H+). High potassium content of cell is release upon cell death leading to the increase in ECF potassium concentration [15,20-22]. Potassium plays an important role in cellular metabolism, especially in protein and glycogen synthesis and in the enzymatic processes necessary for cellular energy. A constant cell potassium concentration is critical for enzyme activities and for cell division and growth. It also aids in maintaining cellular electrical neutrality and osmolality.

Other functions of potassium include acid-base balance, nerve impulse conduction and maintenance of normal cardiac rhythm as well as skeletal and smooth muscle contraction [14]. Conditions where serum potassium levels are below 3.5mEq/L is termed hypokalaemia and can be found in 20% hospitalized patients [23]. Potassium may also be lost through kidney excretion in association with metabolic alkalosis and hyperaldosteronism [22,24]. Potassium levels below 3.0mEq/L can cause a problem with cardiovascular and neuromuscular function causing compromised respiratory function [25]. Hypokalaemia also results in glucose intolerance by depressing insulin release from the pancreas [16,17]. Cardiac and / or respiratory arrest can also result from very low levels of potassium [26]. Hyperkalaemia is a condition where the serum potassium level is above 5.0mEq/L and is most often related to kidney failure due to inadequate kidney function [24]. Hyperkalaemia could lead to fatal arrhythmias if not diagnosed and managed early enough [27]. The aim of this study was therefore to analysis the daily changes in sodium and potassium concentrations in stored blood at 4oC over a 20-day period at a teaching hospital blood bank in Ghana.

We used 28 donated samples obtained at the Komfo Anokye Teaching Hospital, Kumasi-Ghana that had been screened using the protocol of the Transfusion Medicine Unit of the hospital. The bleeding was done using CPDA-1 double bags after which 50mls of the thoroughly mixed blood and anticoagulant was transferred into the satellite bag for storage at 4oC for use in the study; enabling the rest to be used for transfusion purposes. We did 5 electrolyte concentration determinations on each of the 28 samples on day 0 (before blood was initially stored in the fridge), day 5, day 10, day 15 and day 20 of storage. On the respective day of analysis, 2 mls of the blood sample was placed into a gel tube and spun at 1500rpm for 3minutes to obtain the plasma. The plasma was then analyzed using the Roche 9180 ISE Electrolyte Analyser (Hoffmann-La Roche Ltd, Switzerland).

Figure 1 shows the mean sodium and potassium levels of all the samples in relation to the various days' readings. It shows a gradual consistent reduction in sodium concentration having reduced from a mean of 155mmol/l to 145.04mmol/l, a change of approximately 10mmol/l over the 20-day period. The potassium levels on the other hand shot up sharply from 3.31mmol/l on day 0 to 8.66mmol/l on day 5 and further to 12.83mmol/l on day 10 after which the rise seemed to have slowed reading 14.19mmol/l on day 15 and 14.98mmol/l on day 20. Table 1 shows the mean changes in the electrolyte concentration over the 20-day period. There is a daily change in potassium concentration of 1.08mmol/l during the first five days of storage; day 6 to day 10 recorded a daily potassium change of 0.84mmol/l; day 11 to day 15 recorded a 0.28mmol/l daily change whiles day 16 to day 20 recorded daily change 0.16mmol/l giving an overall average daily potassium change of 0.59mmol/l over the 20-day period. In terms of the sodium concentration, there was a change of 0.61mmol/l during the first five days of storage; day 6 to day 10 recorded a daily sodium change of 0.48mmol/l; day 11 to day 15 recorded a 0.54mmol/l daily change whiles day 16 to day 20 recorded daily change 0.36mmol/l giving an overall average daily sodium change of 0.50mmol/l over the 20-day period.

Sodium as the primary ECF cation is expected to have a reference range of 145-155mmol/l plasma concentration. This project saw a reduction in ECF sodium concentration in line with work done by Wallas (1979, 2010). The mean total sodium concentration over the period was seen to have dropped from a level of 155mmol/l to a level of 145.04mmol/l (Figure 1). This drop is of great significance and concern due to the numeric variation occurring between readings (Table 1). It is observed that there was a change of 0.61mmol/l during the first five days of storage; day 6 to day 10 recorded a daily sodium change of 0.48mmol/l; day 11 to day 15 recorded a 0.54mmol/l daily change whiles day 16 to day 20 recorded daily change 0.36mmol/l giving an overall average daily sodium change of 0.50mmol/l over the 20-day period. This average daily change is likely to move sodium concentrations in stored blood to level outside the normal reference range as it is stored over time and this holds possible adverse clinical effect on recipients of such units. This is likely to increase the chances of such recipient being prone to oedema as collaborated by Metheny [28] especially in patients with low sodium intake or those experiencing diarrhoea. Potassium on the other hand being mainly an ICF cation is expected to have an ECF concentration of 3.5-5.5mmol/l [14,15]. The average potassium concentration for this study from Day 0 through Day 20 (Figure 1) were 3.31mmol/l, 8.66mmol/l, 12.73mmol/l, 14.19mmol/l and 14.98mmol/l showing a steep rise in in potassium concentration in consonance with established work [29,30]. There is a daily change in potassium concentration of 1.08mmol/l during the first five days of storage; day 6 to day 10 recorded a daily potassium change of 0.84mmol/l; day 11 to day 15 recorded a 0.28mmol/l daily change whiles day 16 to day 20 recorded daily change 0.16mmol/l giving an overall average daily potassium change of 0.59mmol/l over the 20-day period. The seemingly sharp drop in the daily change between days 11 and 15 as well as days 16 and 20 can be attributed to the averaging of the readings at 15mmol/l for most of the readings done in the last days as a result of the limitation on the analyser's reading ability. It was realized that the analyser was unable to read potassium concentrations above 15mmol/l leading to all readings above 15mmol/l being truncated at 15mmol/l.

However, there was relatively higher increment in potassium concentrations on day 10 and 15 by 21.4% and 60.7% respectively. The increased in potassium concentrations over the 20-day measurement period correlated with other works by Latham et al., [31] and Ratcliffe et al., [8] who also gave increased concentrations above 25mmol/l during a 21-35 storage period. Concurrently, the average daily change of 0.59mmol/l gotten from this research duly falls in line with work done by Bailey and Bove [7] who stated that plasma level of potassium may increase by 0.5-1.0mmol/L per day of refrigeration. The general decrease in ECF sodium concentration and increase in ECF potassium concentration will also result a concomitant opposite effect in the ICF where sodium and potassium concentrations also changes due to the failure of the sodium-potassium pump. The failure of the Na+/K+ ATPase action during the storage period was first postulated by Wallas [32]; he attributed the failure to an inhibition of the membrane ATPase by the low temperature allowing the unopposed leakage of these electrolytes in and out of the red cells. Normally, the Na+/K+ pump is known to transport 3 sodium ions against 2 potassium ions [33] but from our study , a careful look at the daily changes in the sodium concentration (0.5mmol/l) and potassium changes (0.59mmol/l) shows an almost equal exchange of the two electrolytes between the ECF and ICF as blood is stored in the fridge at 4oC. We can therefore deduce that though there is a failure in the ATPase activity, the resultant occurrence is closely regulated by the sodium - potassium pump.

Due to the increase in potassium level with storage, care is needed in determining age of blood [34], volume transfused at a time and rate of transfusion [35] to minimize hyperkalaemia related blood transfusion complications [4,35,36]. Transfusing hyperkalaemic blood however, may be a transient factor if the recipient's kidneys are functioning properly [2] and the Na+/K+ ATPase is also working efficiently [18,37]. However, this is a great concern in individuals undergoing dialysis [14] due to renal failure.

Authors declare no competing interest.

Clement Opoku-Okrah conceptualized the idea. Benjamin Kojo Safo Acquah and Elliot Eli Dogbe designed the study and performed the laboratory work. Benjamin Kojo Safo Acquah performed the statistical analysis of the data. All the authors contributed to the drafting of this manuscript. Also, they have read and approved the final version.

The authors wish to thank the staff of the Transfusion Medicine Unit and Biochemistry department of Komfo Anokye Teaching Hospital for their advice and assistance. The findings, interpretations and conclusions expressed in this research findings are entirely those of the authors and do not necessarily represent the views of the institutions where they work for or are affiliated with.

Table 1: Bonferroni’s multiple comparison test of variance between the various reading days

Figure 1: mean measurement of electrolyte concentration per reading

1. Buckley MS, Leblanc JM, Cawley MJ. Electrolyte disturbances associated with commonly prescribed medications in the intensive care unit. Critical care medicine. 2010; 38(6):S253-64. PubMed | Google Scholar


2. Hoskote SS, Joshi SR, Ghosh AK. Disorders of potassium homeostasis: pathophysiology and management. J Assoc Physicians India. 2008; 56:685-93. PubMed | Google Scholar


3. Murthy BV, Waiker HD, Neelakanthan K, Majam Das K. Hyperkalaemia following blood transfusion. Postgraduate medical journal. 1999; 75(886):501-3. PubMed | Google Scholar


4. Buntain SG, Pabari M. Massive transfusion and hyperkalaemic cardiac arrest in craniofacial surgery in a child. Anaesthesia Intensive Care. 1999; 27(5):530-3. PubMed | Google Scholar


5. Matthew CA, Frank P, Hurst, Kevin C, Abbott MD, Robert M. Perkins M. Hyperkalemia After Packed Red Blood Cell Transfusion in Trauma Patients. The Journal of TRAUMA Injury, Infection, and Critical Care. 2008; 64(2Supl):S86 -S91. PubMed | Google Scholar


6. Wallas CH. Sodium and Potassium Changes in Blood Bank Stored Human Erythrocytes. Transfusion. 1979; 19(2):210-5. PubMed | Google Scholar


7. Bailey DN, Bove JR. Chemical and hematological changes in stored CPD blood. Transfusion.1975 May-Jun;15(3):244-9. PubMed | Google Scholar


8. Ratcliffe JM, Elliott MJ, Wyse RK, Hunter S, Alberti KG. The metabolic load of stored blood: Implications for major transfusions in infants. Arch Dis Child. 1986; 61(12):1208-14. PubMed | Google Scholar


9. Zauder HL. Massive transfusion. International anesthesiology clinics. 1982; 20(4):157-70. PubMed | Google Scholar


10. Hall TL, Barnes A, Miller JR, Bethencourt DM, Nestor L. Neonatal mortality following transfusion of red cells with high plasma potassium levels. Transfusion.1993 Jul;33(7):606-9. PubMed | Google Scholar


11. Sun Y, Mills D, Ing TS, Shapiro JI, Tzamaloukas AH. Body sodium, potassium and water in peritoneal dialysis-associated hyponatremia. Perit Dial Int.2014 May;34(3):253-9. PubMed | Google Scholar


12. Metheny NM. Fluid and Electrolyte Balance. Nursing Consideration: Sullivan, Kelvin; 2012. Google Scholar


13. McCann JAS. Understanding Diseases: Nursing The Series For Clinical Excellence. In: Hager L, Mills EJ, editors.2008. p. 592 - 5. Google Scholar


14. Hoon Young Choi MD, Sung Kyu Ha MD. Potassium Balances in Maintenance Hemodialysis. Electrolytes and Blood Pressure. 2013;11(1):9-16. PubMed | Google Scholar


15. Lederer E, Alsauskas ZC, Mackelaite L, Nayak V. Hyperkalemia eMedicineMedscape (serial on the Internet). 2013 (cited 2013 Jun 2, 2013); (11/11/13): Available from: http://emedicine.medscape.com/article/240903-overview#aw2aab6b2b2. Google Scholar


16. Rowe JW, Tobin JD, Rosa RM, Andres R. Effect of experimental potassium deficiency on glucose and insulin metablism. Metabolism-Clinical and Experimental. 1980; 29(6):498-502. PubMed | Google Scholar


17. Clausen T, Everts ME. Regulation of the Na,K-pump in skeletal muscle. Kidney international. 1989; 35(1):1-13. PubMed | Google Scholar


18. Reyes N, Gadsby DC. Ion permeation through the Na+,K+-ATPase. Nature International weekly journal of science. 2006; 443:470-4. PubMed | Google Scholar


19. Clark BA, Brown RS. Potassium homeostasis and hyperkalemic syndromes. Endocrinol Metab Clin North Am. 1995; 24(3): 573-91. PubMed | Google Scholar


20. Filho JAR, Nani RS, D'Albuquerque LAC, Holms CA, Rocha JPS, Malbouisson LMS, Machado MCC, Carmona MJC, Auler Júnior JOC. Hyperkalemia accompanies hemorrhagic shock and correlates with mortality. SciELO - Scientific Electronic Library Online (serial on the Internet). 2009; Clinics vol.64 no.6 São Paulo June 2009(6): Available from: http://www.scielo.br/scielo.php?pid=S1807-59322009000600016&script=sci_arttext&tlng=es. Google Scholar


21. Stöppler MC. Hyperkalemia (High Blood Potassium). eMedicineHealth (serial on the Internet).2013;(18/10/2013)Availablefrom: http://www.medicinenet.com/hyperkalemia/article.htm.. PubMed | Google Scholar


22. Adrogue HJ, Madias NE. Changes in plasma potassium concentration during acute acid-base disturbances. American Journal of Medicine. 1981; 71(3):456-67. PubMed | Google Scholar


23. Paice BJ, Paterson KR, Onyangaomara F, Donnelly T, Gray JMB, Lawson DH. Record linkage study of hypokalemia in hospitalized patients. Postgraduate medical journal. 1986; 62(725):187-91. PubMed | Google Scholar


24. Blumberg A, Weidmann P, Ferrari P. Effect of prolonged bicarbonate administration on potassium in terminal renal failure. Kidney international. 1992; 41(2):369-74. PubMed | Google Scholar


25. Schulman M, Narins RG. Hypokalemia and cardiovascular disease. American Journal of Cardiology. 1990; 65(10):E4-E9. PubMed | Google Scholar


26. Baltazar RF. Hypokalaemia. In: McMillan L, editor. Basic and Bedside Electrocardiography: Lippincott Williams & Wilkins; 2009 p. 407. Google Scholar


27. Evans KJ, Greenberg A. Hyperkalemia: a review. J Intensive Care Med. 2005; 20(5):272-90. PubMed | Google Scholar


28. Metheny NM. Fluid and electrolyte balance: Nursing considerations. Jones & Sudbury,MA: Bartlett Learning; 2012; 5th Ed. Google Scholar


29. Wallas CH. Red cell changes during storage. Transfus Apher Sci. 2010; 43(1):51-9. PubMed | Google Scholar


30. Vraets A, Lin Y, Callum JL. Transfusion-Associated Hyperkalemia. Transfusion Medicine Reviews. 2011; 25(3):184 - 96. PubMed | Google Scholar


31. Latham JT, Weirich FL. Chemical and hematological changes in stored CPDA-1 blood. Transfusion. 1982; 22(2):158-9. PubMed | Google Scholar


32. Wallas CH. Sodium and potassium changes in blood bank stored human erythroytes. Transfusion. 1979; 19(2):210-5. PubMed | Google Scholar


33. Reyes N, Gadsby DC. Ion permeation through the Na+,K+-ATPase. Nature 2006; 443(7110): 470-474. Google Scholar


34. Vandromme MJ, McGwin G, Jr Weinberg JA. Blood transfusion in the critically ill: does storage age matter? Scandinavian journal of trauma, resuscitation and emergency medicine. 2009; 17(35):35. PubMed | Google Scholar


35. Davies JR. Hyperkalaemia and rapid blood transfusion. Anaesthesia.2000;55(9):928 - 9. PubMed | Google Scholar


36. Sihler KC, Napolitano LM. Complications of Massive Transfusion. Chest. 2010; (137):209-20. PubMed | Google Scholar


37. Morth JP, Pedersen BP, Toustrup-Jensen MS, Sørensen TL-M, Petersen J, Andersen JP, Vilsen B, Nissen P. Crystal structure of the sodium-potassium pump. Nature International weekly journal of science. 2007; 38(450):1043-9. PubMed | Google Scholar