title: Metabolic and toxicological considerations for sepsis drug treatments.
abstract: BACKGROUND
  Sepsis, a complex interaction between pathogen and host response, presents a difficult challenge for clinicians and researchers alike. With an increasing understanding of the pathophysiology of the disease, new treatment paradigms are evolving.
  
  
  METHODS
  This article reviews the metabolic and toxicological considerations in sepsis, including the unique issues involved in neonatal and pediatric populations that differentiate it from adult sepsis. The authors cover metabolic issues, such as perfusion, renal and hepatic dysfunction and fluid retention in conjunction with their impact on therapy. Furthermore, the authors examine toxicological considerations of nephrotoxicity, ototoxicity and adverse drug reactions. The authors also present novel biomarkers of sepsis and current clinical tests utilized for the diagnosis of sepsis, as well as the limitations in animal models of sepsis and newer therapies. An extensive literature search including relevant formulae, publications and textbooks serves as the basis for this review.
  
  
  CONCLUSIONS
  Improving understanding of the metabolic and toxicological issues in sepsis will allow the development of more effective multifaceted treatments and reduction of risks. Clinical research will need to more heavily involve neonatal and pediatric patients given the number of individuals who die from sepsis within these special populations. Development of a sepsis-specific inflammatory biomarker would allow more rapid detection as well as a method to determine the effectiveness of novel therapies.
authors.affiliation: University of Utah School of Medicine, Division of Clinical Pharmacology, Department of Pediatrics, Salt Lake City, UT 48108, USA.
authors.forename: Sarah C
authors.initials: SC
authors.lastname: Campbell
authors.forename: Michael G
authors.initials: MG
authors.lastname: Spigarelli
authors.forename: Joshua
authors.initials: J
authors.lastname: Courter
authors.forename: Catherine Mt
authors.initials: CM
authors.lastname: Sherwin
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000009:adverse effects* / Q000378:metabolism*; D006801:Humans; D007674:Kidney Diseases / Q000139:chemically induced / Q000378:metabolism; D018805:Sepsis / Q000188:drug therapy* / Q000378:metabolism*; D016896:Treatment Outcome
chemical_list: D000900:Anti-Bacterial Agents