Endotoxins dialysis solutions

Endotoxin-free solutions require the use of bacterial endotoxin free starting materials. For dialysis solutions separate requirements exist, see Sect. 14.4.2. 

However, the limit should be even lower a patient receives 60 L of water per dialysis treatment. A treatment lasts for 3 h. That means an intravenous administration of 20 L in 1 h. According to the Ph. Eur. the allowed maximum amount of bacterial endotoxins for parenteral use is 5 lU per kg bodyweight in 1 h. This means for a 60 kg patient that 300 lU bacterial endotoxins are allowed to be present in 20 L resulting in a requirement of <0.015 lU/mL. At this moment the assay technique allows an endotoxin limit of 0.025 lU/ mL to be detected and present water treatment units are able to produce water of this quality. This topic and other requirements are under discussion within the Ph. Eur. committee on dialysis solutions. 

The monograph Water, purified of the Ph. Eur. set limits for total organic carbon (TOC) or oxidisable substances, endotoxins (if intended for dialysis solutions), conductivity and the following ions nitrates, aluminium (if intended for dialysis solutions) and heavy metals. In addition it is necessary to perform microbiological monitoring during production and storage. For purified water in containers, the Ph.Eur. 

Adsorbents are used in medicine mainly for the treatment of acute poisoning, whereas other extracorporeal techniques based on physico-chemical principles, such as dialysis and ultrafiltration, currently have much wider clinical applications [1]. Nevertheless, there are medical conditions, such as acute inflammation, hepatic and multi-organ failure and sepsis, for which mortality rates have not improved in the last forty years. These conditions are usually associated with the presence of endotoxin - lipopolysaccharide (LPS) or inflammatory cytokines - molecules of peptide/protein nature [2]. Advantages of adsorption over other extracorporeal techniques include ability to adsorb high molecular mass (HMM) metabolites and toxins. Conventional adsorbents, however, have poor biocompatibility. They are used coated with a semipermeable membrane of a more biocompatible material to allow for a direct contact with blood. Respectively, ability of coated adsorbents to remove HMM solutes is dramatically reduced. In this paper, preliminary results on adsorption of LPS and one of the most common inflammatory cytokines, TNF-a, on uncoated porous polymers and activated carbons, are presented. The aim of this work is to estimate the potential of extracorporeal adsorption technique to remove these substances and to relate it to the porous structure of adsorbents. 

Because irrigations are used in or on body areas that are usually sterile or have a low degree of contaminatiOTi, there are strict requirements for their production and quality control. In this chapter the use, the design of formulation and preparation method as well as the on site preparation of irrigations will be discussed. With regard to solutions for various types of dialysis, the use of concentrates, the water quality and the requirements for bacterial endotoxins are fully discussed. 

The Ph. Eur. requires solutions for haemodialysis, after dilution, to contain not more than 0.5 lU/mL. Solutions for haemo(dia)filtration and peritoneal dialysis have to be sterile and should not contain more than 0.05 lU/mL bacterial endotoxins according to the present Ph. Eur. requirements (Ph. Eur. 8.0). During a haemo(dia)filtration treatment a large volume of the solution is administered parenterally to the patient (about 60 L per dialysis session). The more stringent requirement for bacterial endotoxins in solutions for haemo(dia)filtration compared to that for solutions for haemodialysis is due to the large volume of solution administered with the first technique. 

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See also in sourсe #XX -- [ ]

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