title: IgM-Enriched Immunoglobulin Attenuates Systemic Endotoxin Activity in Early Severe Sepsis: A Before-After Cohort Study.
abstract: BACKGROUND
  Sepsis remains associated with a high mortality rate. Endotoxin has been shown to influence viscoelastic coagulation parameters, thus suggesting a link between endotoxin levels and the altered coagulation phenotype in septic patients. This study evaluated the effects of systemic polyspecific IgM-enriched immunoglobulin (IgM-IVIg) (Pentaglobin® [Biotest, Dreieich, Germany]) on endotoxin activity (EA), inflammatory markers, viscoelastic and conventional coagulation parameters.
  
  
  METHODS
  Patients with severe sepsis were identified by daily screening in a tertiary, academic, surgical ICU. After the inclusion of 15 patients, the application of IgM-IVIg (5 mg/kg/d over three days) was integrated into the unit's standard operation procedure (SOP) to treat patients with severe sepsis, thereby generating "control" and "IgM-IVIg" groups. EA assays, thrombelastometry (ROTEM®) and impedance aggregometry (Multiplate®) were performed on whole blood. Furthermore, routine laboratory parameters were determined according to unit's standards.
  
  
  RESULTS
  Data from 26 patients were included. On day 1, EA was significantly decreased in the IgM-IVIg group following 6 and 12 hours of treatment (0.51 ±0.06 vs. 0.26 ±0.07, p<0.05 and 0.51 ±0.06 vs. 0.25 ±0.04, p<0.05) and differed significantly compared with the control group following 6 hours of treatment (0.26 ±0.07 vs. 0.43 ±0.07, p<0.05). The platelet count was significantly higher in the IgM-IVIg group following four days of IgM-IVIg treatment (200/nl ±43 vs. 87/nl ±20, p<0.05). The fibrinogen concentration was significantly lower in the control group on day 2 (311 mg/dl ±37 vs. 475 mg/dl ±47 (p = 0.015)) and day 4 (307 mg/dl ±35 vs. 420 mg/dl ±16 (p = 0.017)). No differences in thrombelastometric or aggregometric measurements, or inflammatory markers (interleukin-6 (IL-6), leukocyte, lipopolysaccharide binding protein (LBP)) were observed.
  
  
  CONCLUSIONS
  Treatment with IgM-enriched immunoglobulin attenuates the EA levels in patients with severe sepsis and might have an effect on septic thrombocytopenia and fibrinogen depletion. Viscoelastic, aggregometric or inflammatory parameters were not influenced.
  
  
  BACKGROUND
  clinicaltrials.gov NCT02444871.
authors: Department of Anesthesia, Intensive Care Medicine and Pain Therapy, University Hospital Frankfurt, Frankfurt am Main, Germany.|Clinic for Anaesthesiology, University Hospital Goettingen, Goettingen, Germany.
authors: Saskia
authors: S
authors: Wand
authors: Department of Anesthesia, Intensive Care Medicine and Pain Therapy, University Hospital Frankfurt, Frankfurt am Main, Germany.
authors: Matthias
authors: M
authors: Klages
authors: Department of Anesthesia, Intensive Care Medicine and Pain Therapy, University Hospital Frankfurt, Frankfurt am Main, Germany.
authors: Christin
authors: C
authors: Kirbach
authors: Department of Anesthesia, Intensive Care Medicine and Pain Therapy, University Hospital Frankfurt, Frankfurt am Main, Germany.
authors: Joanna
authors: J
authors: Warszawska
authors: Department of Anesthesia, Intensive Care Medicine and Pain Therapy, University Hospital Frankfurt, Frankfurt am Main, Germany.
authors: Patrick
authors: P
authors: Meybohm
authors: Department of Anesthesia, Intensive Care Medicine and Pain Therapy, University Hospital Frankfurt, Frankfurt am Main, Germany.
authors: Kai
authors: K
authors: Zacharowski
authors: Department of Anesthesia, Intensive Care Medicine and Pain Therapy, University Hospital Frankfurt, Frankfurt am Main, Germany.
authors: Alexander
authors: A
authors: Koch
mesh_terms: D000368:Aged; D015415:Biomarkers / Q000378:metabolism; D015331:Cohort Studies; D004731:Endotoxins / Q000633:toxicity*; D005260:Female; D006801:Humans; D007075:Immunoglobulin M / Q000494:pharmacology* / Q000627:therapeutic use; D007249:Inflammation / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D018805:Sepsis / Q000139:chemically induced* / Q000188:drug therapy* / Q000378:metabolism
chemical_list: D015415:Biomarkers; D004731:Endotoxins; D007075:Immunoglobulin M