Evaluation of the potential adverse effects associated with calcium carbonate precipitate during continuous veno-venous hemofiltration (CVVH)

Purpose: This study evaluated the potential adverse effects associated with exposure to calcium carbonate precipitate in Accusol 35 Solution (Accusol 35) during CVVH. Methods: 14 dogs were anesthetized, instrumented, and received CVVH with the test (6) or negative control article (8) for 6 hr. The test article was Accusol 35 with induced precipitate formation prior to CVVH, containing visible particles and sub-visible particles 36-times higher than the maximum concentration specified in European Pharmacopoeia (EP). The negative control article was Accusol 35 conforming to EP specification. One-half the dogs in the negative control article group received a central venous injection of Sephadex G-50® beads (10 mg/kg) following CVVH as positive control. Select cardiovascular (CV) parameters were measured throughout CVVH. Arterial samples were obtained for blood gas analysis. Samples of the test and negative control articles were obtained hourly during CVVH for determination of pH and subvisible particles. Dogs were euthanized and lung tissue samples were examined histologically. Results: All CV parameters remained stable and no differences were observed between the test and negative control articles. Sephadex beads caused an increase (p 0.05) in PO2 and an increase (p>0.05) in PCO2. No differences in lung histology were observed between the test and negative control articles. The lungs from all dogs given Sephadex beads contained multiple intravascular particles in large caliber blood vessels. Conclusion: CVVH performed on anesthetized dogs for 6 hr using Accusol 35 containing visible and sub-visible particles 36-times higher than the maximum concentration specified in EP, resulted in no adverse effects on CV parameters, blood gases and electrolytes, and lung histology as compared with Accusol 35 containing no visible particles and sub-visible particles that were within EP specification. Evaluation of the Potential Adverse Effects Associated with Calcium Carbonate Precipitate During Continuous Veno-venous Hemofiltration (CVVH) D. Pantaleone1; J. McKee2; B. Brooks2; J. Daller2; J. Gass2; P. Zieske1; P. Mussi3; B. Moreaux3 1, 2, 3Baxter Healthcare Corporation, 1McGaw Park, IL, USA, 2Round Lake, IL, USA, 3Braine-l'Alleud, Belgium P365