The USP MER Program results of KCL error reports led to the following FDA labeling changes #1 - to give more prominence to the need to dilute the product prior to use;
Endotoxins are potent activators of the complement system and other immunoregulators (IL6, TNF , cytokines) host responses to endotoxin are dose dependent and include pyrogenic reactions, shock, decrease in SBP, and death bicarbonate concentrate unlike acetate concentrate can support rapid bacterial growth and endotoxin production HD with non sterile dialysate has been shown to be associated with greater interleukin 1 production than with sterile dialysate in a grp of HD patients shifted for one month from non sterile bicarbonate dialysate to ultrapure bicarbonate dialysate, plasma levels of IL 1 and TNF were found to decrease significantly levels of 2 microglobulin and and the incidence of carpel tunnel syndrome were lower in patients on ultrapure dialysate use of sterile endotoxin free dialysate is advocated bacterial products such as endotoxins are potent stimuli of inflammatory reactions through complement activation, increased monokine production & up regulation at the surface of leukocytes of molecules involved in cell adhesion and activation Tielemans showed that bacterial contamination of bicarbonate dialysate, at levels associated with clinical hemodialysis, neither enhanced the level of complement activation nor the secretion of monokines IL6 and TNF (Tielemans C et al. Effects of ultrapure and non-sterile dialysate on the inflammatory response during in vitro hemodialysis. KI 1996; 49: 236-243.)
Replacement fluid must be sterile Whether dialysate must be sterile or ultra pure depend on whether there is back filtration or back diffusion Back filtration depends on pressure profiles and membrane permeability Synthetic high flux membranes allow less back diffusion than cellulose high or low flux membranes
CRRT Complications and Troubleshooting Sheldon Tobe, Sunnybrook Health Sciences Centre
Immediate Use Exemption from ISO Class 5 (Class 100)
Three or fewer sterile products may be prepared in worse than ISO Class 5 air when there is no direct contact contamination, and administration begins within 1 hour and is completed within 12 hours of preparation.