title: Adverse effects associated with high-dose recombinant human bone morphogenetic protein-2 use in anterior cervical spine fusion.
abstract: METHODS
  A retrospective review of patients who underwent an anterior cervical fusion using recombinant human bone morphogenetic protein (rhBMP)-2 with an absorbable collagen sponge (INFUSE; Medtronic Sofamor Danek, Minneapolis, MN).
  
  
  OBJECTIVE
  To ascertain the complication rate after the use of high-dose INFUSE in anterior cervical fusions.
  
  
  BACKGROUND
  The rhBMP-2 has been primarily investigated in lumbar spine fusions, where it has significantly enhanced the fusion rate and decreased the length of surgery, blood loss, and hospital stay.
  
  
  METHODS
  We present 151 patients who underwent either an anterior cervical discectomy and fusion (n = 138) or anterior cervical vertebrectomy and fusion (n = 13) augmented with high-dose INFUSE between July 2003 and March 2004. The rhBMP-2 (up to 2.1 mg/level) was used in the anterior cervical discectomy and fusions.
  
  
  RESULTS
  A total of 35 (23.2%) patients had complications after the use of high-dose INFUSE in the cervical spine. There were 15 patients diagnosed with a hematoma, including 11 on postoperative day 4 or 5, of whom 8 were surgically evacuated. Thirteen individuals had either a prolonged hospital stay (> 48 hours) or hospital readmission because of swallowing/breathing difficulties or dramatic swelling without hematoma.
  
  
  CONCLUSIONS
  A significant rate of complications resulted after the use of a high dose of INFUSE in anterior cervical fusions. We hypothesize that in the cervical area, the putative inflammatory effect that contributes to the effectiveness of INFUSE in inducing fusion may spread to adjacent critical structures and lead to increased postoperative morbidity. A thorough investigation is warranted to determine the optimal dose of rhBMP-2 that will promote cervical fusion and minimize complications.
authors.affiliation: Department of Neurological Surgery, University of Louisville School of Medicine, Louisville, KY 40292, USA. cbshields1@aol.com
authors.forename: Lisa B E
authors.initials: LB
authors.lastname: Shields
authors.forename: George H
authors.initials: GH
authors.lastname: Raque
authors.forename: Steven D
authors.initials: SD
authors.lastname: Glassman
authors.forename: Mitchell
authors.initials: M
authors.lastname: Campbell
authors.forename: Todd
authors.initials: T
authors.lastname: Vitaz
authors.forename: John
authors.initials: J
authors.lastname: Harpring
authors.forename: Christopher B
authors.initials: CB
authors.lastname: Shields
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins / Q000009:adverse effects*; D018786:Bone Substitutes; D002574:Cervical Vertebrae / Q000601:surgery*; D017586:Diskectomy; D005260:Female; D006801:Humans; D016268:Internal Fixators; D008297:Male; D008875:Middle Aged; D016348:Osseointegration / Q000187:drug effects; D011183:Postoperative Complications / Q000209:etiology*; D011994:Recombinant Proteins / Q000009:adverse effects*; D012189:Retrospective Studies; D013123:Spinal Fusion / Q000009:adverse effects* / Q000295:instrumentation / Q000379:methods; D015503:Surgical Sponges; D016212:Transforming Growth Factor beta / Q000009:adverse effects*
chemical_list: D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins; D018786:Bone Substitutes; D011994:Recombinant Proteins; D016212:Transforming Growth Factor beta; C499469:recombinant human bone morphogenetic protein-2