Efficiency of Emulsified Particle-Associated Polyhexamethylenbiguanid-Hydrochlorid (Polihexanide) for Peritoneal Lavage in a Murine Sepsis Model

Abstract

Background: Peritoneal lavage is often used for peritonitis, however, the volume and type of lavage fluid varies. Saline or Ringer's solution are used most often and lavage is performed until the fluid is clear. However, at present there is no irrigation fluid for peritoneal lavage with residual antiseptic activity. Because the combination of aqueous polyhexamethylenbiguanid-hydrochlorid (PHMB) and egg phosphatidylcholine containing oil/water emulsions (Lipofundin^® MCT 20%, B. Braun AG, Melsungen, Germany) protect mammalian cells without neutralizing the antiseptic effect of PHMB, it seemed promising to investigate such human cell protecting, yet antibacterial combination for peritoneal lavage in a murine sepsis model.

Methods: After induction of colon ascendens stent peritonitis (CASP) in mice, the foci were eradicated by re-laparotomy, followed by twofold lavage with 2 × 3 mL of the tested emulsion. The following lavage fluids were investigated blindly: 10% Lipofundin/0.05% PHMB, 100% Lipofundin, 0.05% PHMB, and 0.9% saline. After 24 hours the animals were euthanized and organs, blood, and lavage fluid were examined for cytokine levels (tumor necrosis factor [TNF]-α, interferon [IFN]-γ, interleukin [IL]-6, IL-10), liver enzymes (alanine aminotransferase [ALT], aspartate aminotransferase [AST], gamma-glutamyltransferase [gamma-GT], glutamate dehydrogenase [GLDH]), creatinine, and bacterial density.

Results: Only the combination of Lipofundin/PHMB (n = 23) increased the survival rate. Compared with saline alone, PHMB alone decreased the survival rate. Twenty-four hours after induction of peritonitis, the lowest number of colony forming units (CFU) was observed after lavage with PHMB/Lipofundin in all examined organs, blood, and lavage fluid (p < 0.01). Alanine aminotransferase, AST, and creatinine levels were increased after lavage with PHMB compared with the other lavage fluids (p < 0.05).

Conclusions: Peritoneal lavage using 0.05% aqueous PHMB alone resulted in no survival benefit in a CASP murine model. The increase of liver enzymes and creatinine seem to be a toxic side effect of PHMB. However, an emulsion of 0.05% PHMB/10% Lipofundin decreased cytotoxicity while maintaining antiseptic efficiency. The advantage for survival was explained by decrease of bacterial load in organs, blood, and lavage fluid. The results provide a new option for the treatment of peritonitis using peritoneal lavage with the combination of PHMB/Lipofundin.

Keywords: antiseptic efficacy; colon ascendens stent peritonitis (CASP); peritoneal lavage; polihexanide o/w emulsion; polyhexamethylen-biguanid-hydrochlorid; polyhexanide.