Effect of incubation with crystalloid solutions or medications on packed red blood cells

Abstract

BACKGROUND American Association of Blood Banks (AABB) guidelines suggest that packed red blood cells (PRBCs) be administered through a dedicated intravenous (IV) catheter. Literature supporting this broad‐scope declaration are scarce. Obtaining additional IV access is painful, costly, and an infectious risk. We evaluated the effect of co‐incubating PRBCs with crystalloids and medications on PRBC hemolysis, membrane deformability, and aggregation, as well as medication concentration. METHODS PRBCs were co‐incubated 5 minutes with plasma, normal saline (NS), 5% dextrose in water (D5W), Plasmalyte, epinephrine (epi), norepinephrine (norepi), dopamine (dopa), or Propofol (prop). Samples were then assessed for hemolysis (free hemoglobin, serum potassium), membrane deformability (elongation index [EI]), aggregation (smear, critical shear stress [mPa]) and drug concentration (High Performance Liquid Chromatography/Tandem Mass Spectrometry [LCMS‐MS]). Significance (p ≤ 0.05) was determined by Wilcoxon‐paired comparisons or Wilcoxon/Kruskall Willis with post‐hoc Dunn's test. RESULTS Compared to co‐incubation with plasma: 1) co‐incubation resulted in significantly increased hemolysis only when D5W as used (free hemoglobin, increased potassium); 2) EI trended lower when co‐incubated with D5W and trended toward higher when co‐incubated with prop; 3) aggregation was significantly lower when PRBCs co‐incubated with NS, D5W, or Plasmalyte, and trended lower when co‐incubated with epi, norepi, or dopa. Medication concentrations were between those predicted by distribution only in plasma and distribution through the entire intra‐ and extracellular space. CONCLUSION Our data suggest that 5 minutes of PRBC incubation with isotonic crystalloids or catecholamines does not deleteriously alter PRBC hemolysis, membrane deformability, or aggregation. Co‐incubation with D5W likely increases hemolysis. Propofol may promote hemolysis.

Mixing commonly used crystalloid solutions with red blood cells in five common additives does not negatively impact hemolysis, aggregometry, or deformability

“…13 The lack of an aggregation-promoting effect of crystalloids is consistent with what we observed when mixing crystalloids with additive-free RBC preparations. 9 LR, a calciumcontaining crystalloid, also failed to promote aggregation when mixed with additive-containing RBCs in our studies. The effect of calcium-containing crystalloids on RBCs mixed in additives is likely condition dependent.…”

“…Though hemolysis levels within any additive group tended to be relatively high or highest when the additive was D5W, all of our upper‐limit 95% CIs are less than one‐third of those felt to be clinically relevant 12 . The additives appear to protect against the increase in hemolysis we previously observed when mixing D5W with additive‐free RBC concentrates 9,16 . One may speculate that dextrose‐containing additives themselves cause dextrose‐related hemolysis at the time of initial mixing with RBCs, thereby making irrelevant the fact that no additional hemolysis is observed when later mixing with D5W 17 .…”

“…24 Similarly, longer mixing times may alter the response of RBCs to crystalloid exposure. [45][46][47] Though our prior work suggests that mixing catecholamines into the crystalloids does not deleteriously effect deformability, aggregometry, or hemolysis of additivefree RBCs, 9 we did not evaluate the influence of medications in the present study. Finally, we used RBCs that were not irradiated.…”

“…12 The additives appear to protect against the increase in hemolysis we previously observed when mixing D5W with additive-free RBC concentrates. 9,16 One may speculate that dextrose-containing additives themselves cause dextrose-related hemolysis at the time of initial mixing with RBCs, thereby making irrelevant the fact that no additional hemolysis is observed when later mixing with D5W. 17 However, hemolysis is known to be minimized by inclusion of the additive recipes in comparison to additive-free RBCs.…”

“…PRBC hemolysis, as indicated by free hemoglobin present in the supernatant overlying a centrifuged sample of RBCs-medication solution, was measured at room temperature. 9 Peak absorption at 380 nm, 415 nm, and 450 nm was measured (FlexStation 3, Molecular Devices, San Jose, CA), and free hemoglobin concentration (mg/L) was determined using the formula ([(167.2 × Absorption 415 nm )-(83.6 × Absorption 380 nm )-(83.6 × Absorption 450 nm )](dilution/1000). 10 This value was multiplied by 10 −4 and presented as grams per deciliter plasma.…”