WHAT I DO Possible Future Method to Prevent Transfusion Associated Hyperkalemia Chisa Yamada, M.D. Transfusion Medicine Background Hyperkalemia is a life-threatening possible complication of blood transfusion, associated with the development of arrhythmias leading to cardiac arrest. Stored RBCs in 4 °C leak intracellular K due to the inhibition of the membrane ATP pump and decreased ATP. Gamma irradiation increases K leak further. Biochemical Change of Stored Red Blood Cells (Technical Manual, 15th edition) Age of the Units and Potassium K concentration (mmol/L) 80 70 60 50 Irradiated Units Non-irradiated Units 40 30 20 10 0 0 20 40 Age of RBC unit (days) 60 80 Recovery of cellular K at 37°C Likely mediated by Na-K pump, and Na-K-Cl cotransport (Brugnara, et al. Transfusion 1992; 5032(3):246252) Patients at Risk Any patient who needs rapid and massive transfusions, especially those with small total blood volume such as neonates Children: Adults: Cardiac surgery CV by-pass circuit prime Extracorporeal membrane oxygenation Exchange transfusion Trauma Trauma Liver transplant surgery Potassium Infusion Rates Daily K infusion recommendation for neonates 2 – 3 mEq/Kg/24 hr = 0.0014 – 0.0021 mEq/Kg/min K dose by 42 d old AS-3 RBC transfusion 10 mL RBC transfusion to 1 Kg infant in 3 hours 0.0010 mEq/Kg/min 50 mL RBC transfusion to 1 Kg infant in 1 hour 0.0153 mEq/Kg/min 50 mL RBC transfusion to 1 Kg infant in 1 hour – How much K concentration is acceptable? 6.3 mEq/L Age of the Units and Potassium K concentration (mmol/L) 80 70 60 50 Irradiated Units Non-irradiated Units 40 30 20 10 0 0 20 40 Age of RBC unit (days) 60 80 Current Effort Fresher units (<5-7 day old) Not always available. Washing With 1-2 L of normal saline Up to 20% of RBCs may be lost. Takes up to 1 hour. Use within 24 hours after washing. – Normal saline re-suspended RBCs do not store well. – K re-accumulates in normal saline. – Need washing relatively short period prior to transfusion. Timing of irradiation Up to the facility. Recommendations from Society of Pediatric Anesthesiology 1. Transfuse fresh RBC (<7 days old) in massive transfusion cases. 2. Transfuse the irradiated blood as soon as possible. 3. If only RBC units with relatively high K are available, Avoid a hypovolemia-associated low cardiac output state and replace blood loss early. Request washed RBC, possible use of Cell Saver ®. Transfuse slowly with possible >23 gauge peripheral IV rather than via a central venous catheter. Check serum electrolytes frequently. (The Pediatric Anesthesia Quality Improvement initiative 8/16/2011) Response from AABB 1. The safe concentration of extracellular K in transfused units has 2. 3. 4. 5. 6. not been determined. No data is available about K increase in short period after irradiation. Washing RBCs requires time which may not be consonant with rapid blood transfusion situations. Washing RBCs can induce hemolysis and can increase K concentration more. Perioperative salvage technology (e.g., Cell Saver ®) has not been FDA-approved to wash allogeneic blood at this point. Additional approaches: Management and monitoring of K before and during the transfusion. Use of additive units rather than CPDA-1 units, but safety data for neonates has not been studied. Supernatant removal. (http://www.aabb.org/pressroom/Pages/hyperkalemia110914.aspx) Future Possibility Take out potassium from RBC units by medical device Perioperative salvage technology (e.g., Cell Saver ®) to wash RBC units? Small dialysis filter? Potassium/Sodium exchange filter? Potassium Adsorption Filter : KPF-4® Developed and approved for use in Japan (KPF-4®, Kawasumi Laboratories Inc., Tokyo, Japan). Made with sodium polystyrene sulfonate resin. Mechanism of action : exchanges K with Na. Potassium Adsorption Filter : KPF-4® (KPF-4®, Kawasumi Laboratories Inc., Tokyo, Japan) In Vitro evaluation of efficacy of KPF-4® Use leukoreduced AS-3 RBC units of variable ages (6-61 days) One KPF-4® was used to filter three RBC units with variable flow rates by gravity (18.3-65.9 mL/min) 10 filters and a total of 30 RBC units, 18 irradiated units and 12 non-irradiated units, were tested (Yamada, et al. Transfusion 2010; 50(9):1926-1933) Potassium (mmol/L) ( Reference range 3.5-5.1 mmol/L ) Pre filtering: 13.7 - 73.5 mmol/L, Post: 0.2 - 16.2 mmol/L mmol/L 1st Units 2nd Units 3rd Units 80 70 60 50 40 30 20 10 0 Pre Post Pre Post Pre Post (Yamada, et al. Transfusion 2010; 50(9):1926-1933) Average % Change After Filtering Unit Na K Cl Mg tCa RBC Hb Hct 1 (n=10) +42.5 -97.5 +12.4 +184.4 +144.2 -6.9 -7.7 -7.2 2 (n=10) +36.6 -91.2 +0.2 +192.8 +130.4 -1.7 -1.7 -1.6 3 (n=10) +19.9 -64.4 -0.8 +77.1 +73.6 -1.6 -0.8 -0.9 No change in pH, iCa, plasma Hb, glucose level (Yamada, et al. Transfusion 2010; 50(9):1926-1933) Thank you!