Adverse Effects Associated With High-Dose Recombinant Human ... : Spine (original) (raw)

Cervical Spine

Adverse Effects Associated With High-Dose Recombinant Human Bone Morphogenetic Protein-2 Use in Anterior Cervical Spine Fusion

Shields, Lisa B. E. MD*; Raque, George H. MD*; Glassman, Steven D. MD†; Campbell, Mitchell MD†; Vitaz, Todd MD*; Harpring, John MD*; Shields, Christopher B. MD*

From the Departments of *Neurological Surgery and †Orthopedic Surgery, University of Louisville School of Medicine, Louisville, KY.

Acknowledgment date: October 26, 2004. First revision date: December 7, 2004. Second revision date: February 7, 2005. Third revision date: March 11, 2005. Acceptance date: March 14, 2005.

The device(s)/drug(s) that is/are the subject of this manuscript is/are not FDA-approved for this indication and is/are not commercially available in the United States. No funds were received in support of this work.

One or more of the author(s) has/have received or will receive benefits for personal or professional use from a commercial party related directly or indirectly to the subject of this manuscript: e.g., honoraria, gifts, consultancies, royalties, stocks, stock options, decision making position.

Address correspondence and reprint requests to Christopher B. Shields, MD, Department of Neurological Surgery, School of Medicine, University of Louisville, Louisville, KY 40292; E-mail: [email protected]

Study Design.

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.

Summary of Background Data.

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.