title: An evaluation of medications commonly used for epidural neurolysis procedures in a human fibroblast cell culture model.
abstract: OBJECTIVE
  Epidural injections are popular therapies for sciatica and low back pain. Local anesthetics and corticosteroids are commonly used for most injections techniques, but some treatments use a specific combination of several agents. The epidural lysis of adhesions procedure (Racz) uses a combination of bupivacaine, hyaluronidase, a corticosteroid, and hypertonic saline. Because severe complications, some with permanent neurologic deficits, have been observed, we considered the possibility that individual agents or a combination thereof might be capable of damaging or destroying cells in primarily the epidural tissues.
  
  
  METHODS
  We used monolayer cell cultures of human fibroblasts in Dulbecco modified Eagle medium to study these pharmacological agents alone or in combination. Cell viability and proliferation were assessed by Trypan blue staining, cell counts, and the WST-1 assay. Time and concentration series were performed.
  
  
  RESULTS
  With the corticosteroid, we observed the previously described proliferation-retarding effects. Hyaluronidase was not found to have a relevant effect on fibroblast proliferation. Bupivacaine and hypertonic saline were found to have a time- and concentration-dependent effect on cell viability and proliferation. Both were found to be toxic at concentrations well below the ones used clinically.
  
  
  CONCLUSIONS
  We identified a potential for harm caused by commonly used pharmacological agents when applied epidurally. Animal studies will have to show whether the same can be observed in living tissues.
authors.affiliation: Department of Orthopedic Surgery, Grosshadern Medical Center, University of Munich, Marchioninistr., Munich, Germany. christof.birkenmaier@med.uni-muenchen.de
authors.forename: Christof
authors.initials: C
authors.lastname: Birkenmaier
authors.forename: Julia
authors.initials: J
authors.lastname: Redeker
authors.forename: Birte
authors.initials: B
authors.lastname: Sievers
authors.forename: Carolin
authors.initials: C
authors.lastname: Melcher
authors.forename: Volkmar
authors.initials: V
authors.lastname: Jansson
authors.forename: Susanne
authors.initials: S
authors.lastname: Mayer-Wagner
mesh_terms: D000305:Adrenal Cortex Hormones / Q000008:administration & dosage / Q000633:toxicity*; D002045:Bupivacaine / Q000008:administration & dosage / Q000633:toxicity*; D018929:Cell Culture Techniques; D049109:Cell Proliferation / Q000187:drug effects; D004341:Drug Evaluation / Q000379:methods; D004359:Drug Therapy, Combination; D005347:Fibroblasts / Q000187:drug effects* / Q000473:pathology; D006801:Humans; D006821:Hyaluronoglucosaminidase / Q000008:administration & dosage / Q000633:toxicity*; D007268:Injections, Epidural / Q000009:adverse effects; D012462:Saline Solution, Hypertonic / Q000008:administration & dosage / Q000633:toxicity*
chemical_list: D000305:Adrenal Cortex Hormones; D012462:Saline Solution, Hypertonic; D006821:Hyaluronoglucosaminidase; D002045:Bupivacaine