The compatibility of Lactated Ringer's Solution with red-cell-containing human blood products: a systematic review
CCCF ePoster library. Wolfe D. Oct 31, 2016; 150879; 2
Dianna Wolfe
Dianna Wolfe
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Topic: Systematic Review, Meta-analysis, or Meta-synthesis

The compatibility of Lactated Ringer’s Solution with red-cell-containing human blood products: a systematic review

Wolfe, Dianna1; McIntyre, Lauralyn2,3; English, Shane W.2,3; Fergusson, Dean2,3; Kanji, Salmaan2,4; Lalu, Manoj5; Mendis, Nick5; Tinmouth, Alan3
1Knowledge Synthesis Group, The Ottawa Hospital Research Institute, Ottawa, Canada
2Clinical Epidemiology Program, The Ottawa Hospital Research Institute, Ottawa, Canada
3Department of Medicine (Division of Critical Care), University of Ottawa, Ottawa, Canada
4Department of Pharmacy, The Ottawa Hospital, Ottawa, Canada
5Regenerative Medicine Program, The Ottawa Hospital Research Institute, Department of Anesthesiology, The Ottawa Hospital, Ottawa, Canada


INTRODUCTION: Small amounts of calcium in lactated Ringer’s solution may overwhelm the chelating ability of citrate anti-coagulant in red-cell containing blood products, leading to clot formation. Current transfusion guidelines [1] advise against co-administration of red-cell containing blood products and Ringer’s through the same infusion set due to clotting risk. These guidelines were based on experiments conducted in the 1970s; however, blood products and transfusion methods have changed considerably since then, leading clinicians to question the relevancy of current guidelines. Currently, packed red blood cells (PRBCs) with saline-adenine-glucose-mannitol (SAGM) or AS-3 (Adsol, Baxter) additives are transfused in Canada [2].
OBJECTIVE: We conducted a systematic review to assess coagulation outcomes when combining red-cell containing blood products with Ringer’s as compared to other crystalloid solutions in ex vivo experiments.
METHODS: A systematic review protocol was designed a priori, using PICOS criteria based on an ex vivo study design. Searches were systematically conducted in Embase, MEDLINE, BIOSIS, and Web of Science from inception to 21 March 2016. Two independent reviewers screened references for relevance and extracted data using a pre-tested data extraction form. Data were synthesized narratively, according to experimental design (serial dilutions of crystalloid and blood product in test tubes evaluated over time vs. transfusion simulation by infusion of blood and crystalloid through a transfusion set with a filter attached distally to trap potential clot fragments) with a priori subgroups for blood product type, additive, temperature, percentage dilution, type of simulated transfusion (e.g., standard ≥60 min. vs. rapid ≤30 min.), and time of outcome assessment.
RESULTS: Thirteen of 842 references were identified as relevant and included in the analysis. Blood products included whole blood (n = 6) and PRBCs with no additive (n = 5) or with SAGM (n = 1), AS-3 (n = 2), or AS-1 (Nutricel, Pall Medical) (n = 1). Experimental designs included serial dilution (n = 12) and simulated transfusion studies (n = 8). Transfusion studies simulated rapid (n = 4) or standard transfusion (n = 4). Coagulation was assessed visually (n = 13) or by ELISA of prothrombin activation fragment 1+2 (n = 4). Experiments were conducted either at room temperature (n = 11) or 37°C (n = 9). 
Blood products currently used in Canada—PRBCs with SAGM or AS-3—did not clot (determined visually or by ELISA) at room temperature up to 2 hours after mixing at any dilution; SAGM-added PRBCs clotted at 2 and 3 hours for dilutions of ≥50% and ≥25% Ringer’s, respectively, and no dilution of AS-3-added PRBCs clotted before 4 hours. At 37°C, no dilution of AS-3-added PRBCs clotted up to 1 hour (no data for SAGM).  No clots developed in simulated rapid transfusion at 37°C for SAGM or AS-3, or standard transfusion at room temperature for AS-3 (no data for SAGM). No dilution with normal saline caused clotting.
CONCLUSION: The available evidence suggests that at room temperature either SAGM- or AS-3-added PRBCs could be co-administered with Ringer’s under rapid transfusion conditions (≤30 min.) or under standard transfusion conditions for AS-3-added PRBCs only. There is a paucity of data regarding co-administration of SAGM-added PRBCs with Ringer’s under standard transfusion conditions and further research is required to determine if clotting may occur in this setting.   



1.            Chambers K, Letendre P, Whitman L, Clark G: Blood Components. In: Clinical Guide to Transfusion Medicine. Edited by Clark G, Charge S, Online edition edn: Canadian Blood Services; 2013.
2.            D'Amici GM, Mirasole C, D'Alessandro A, Yoshida T, Dumont LJ, Zolla L: Red blood cell storage in SAGM and AS3: a comparison through the membrane two-dimensional electrophoresis proteome. Blood Transfus 2012, 10 Suppl 2:s46-54.

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