title: Patients' safety: is there a systemic release of gentamicin by gentamicin-coated tibia nails in clinical use?
abstract: BACKGROUND
  Osteitis is one of the most serious complications in orthopedic surgery. Expert Tibia Nail (ETN) PROtect™ coated with a biodegradable layer of gentamicin-laden polymer was developed for prophylaxis of osteomyelitis. In systemic administration, gentamicin has only a small therapeutic index and serious side effects; it is potentially nephrotoxic as well as ototoxic. It is not yet known if relevant gentamicin concentrations are released into the systemic circulation after implantation of gentamicin-coated nails. In order to evaluate the patients' risks profiles and increase patient safety, we measured gentamicin levels in pre- and postoperative serum samples of patients undergoing implantation of ETN PROtect.
  
  
  METHODS
  Twenty-five patients who received ETN PROtect between March 2012 and August 2014 were included in this study. Collection of blood samples occurred before the operation, at weeks 1-4, 3 and 6 months, and up to 1 year after the implantation. Measurement of gentamicin levels in serum samples was performed at the central laboratory of Heidelberg University Hospital. Additionally, laboratory parameters, C-reactive protein, leukocyte number, urea and creatinine concentrations were analyzed in routine controls before and after operating and assessed for systemic side effects.
  
  
  RESULTS
  Over the course of this prospective observational study, we were able to determine that gentamicin-coated nails do not release gentamicin into the systemic circulation above the lowest detectable level of 0.2 mg/dL. There were slight increases in the mean inflammation and renal retention markers, but no gentamicin-associated side effects could be linked to implantation. Furthermore, no allergic reactions could be detected during our study.
  
  
  CONCLUSIONS
  Our findings suggest that there is no relevant release of gentamicin into the systemic circulation causing a systemic effect, and serious side effects due to gentamicin-coated tibia nails should not be feared. Postoperative monitoring of renal function does not seem necessary because of the implantation of ETN PROtect.
authors.affiliation: HTRG - Heidelberg Traume Research Group Center for Orthopedics, Trauma and Spinal Cord Injury, University Hospital Heidelberg, Heidelberg, Germany.
authors.forename: Arash
authors.initials: A
authors.lastname: Moghaddam
authors.affiliation: HTRG - Heidelberg Traume Research Group Center for Orthopedics, Trauma and Spinal Cord Injury, University Hospital Heidelberg, Heidelberg, Germany.
authors.forename: Viola
authors.initials: V
authors.lastname: Graeser
authors.affiliation: HTRG - Heidelberg Traume Research Group Center for Orthopedics, Trauma and Spinal Cord Injury, University Hospital Heidelberg, Heidelberg, Germany.
authors.forename: Fabian
authors.initials: F
authors.lastname: Westhauser
authors.affiliation: HTRG - Heidelberg Traume Research Group Center for Orthopedics, Trauma and Spinal Cord Injury, University Hospital Heidelberg, Heidelberg, Germany.
authors.forename: Ulrike
authors.initials: U
authors.lastname: Dapunt
authors.affiliation: HTRG - Heidelberg Traume Research Group Center for Orthopedics, Trauma and Spinal Cord Injury, University Hospital Heidelberg, Heidelberg, Germany.
authors.forename: Till
authors.initials: T
authors.lastname: Kamradt
authors.affiliation: Department of Internal Medicine and Clinical Chemistry, University Hospital Heidelberg, Heidelberg, Germany.
authors.forename: Stefan M
authors.initials: SM
authors.lastname: Woerner
authors.affiliation: HTRG - Heidelberg Traume Research Group Center for Orthopedics, Trauma and Spinal Cord Injury, University Hospital Heidelberg, Heidelberg, Germany.
authors.forename: Gerhard
authors.initials: G
authors.lastname: Schmidmaier
keywords: ETN PROtect; fracture; implant; infection; osteitis; osteomyelitis; pseudoarthrosis; therapy; tibia