- Neurological Surgery, The Albert Einstein College of Medicine, Bronx, NY 10451, and Winthrop University Hospital, Mineola, NY 11501, USA
Nancy E. Epstein
Neurological Surgery, The Albert Einstein College of Medicine, Bronx, NY 10451, and Winthrop University Hospital, Mineola, NY 11501, USA
DOI:10.4103/2152-7806.76147Copyright: © 2011 Epstein NE This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
How to cite this article: Epstein NE. Pros, cons, and costs of INFUSE in spinal surgery. Surg Neurol Int 24-Jan-2011;2:10
How to cite this URL: Epstein NE. Pros, cons, and costs of INFUSE in spinal surgery. Surg Neurol Int 24-Jan-2011;2:10. Available from: http://sni.wpengine.com/surgicalint_articles/pros-cons-and-costs-of-infuse-in-spinal-surgery/
Background:INFUSE (recombinant human bone morphogenetic protein-2 [rh-BMP-2]; Medtronic, Memphis, TN, USA) is approved by the Federal Drug Administration (FDA) only for use with the lumbar tapered fusion device (LT Cage; Medtronic) to perform single-level anterior lumbar interbody fusions (ALIF: L2-S1 levels). INFUSE, however, is widely utilized in an “off-label” capacity for anterior and/or posterior cervical, thoracic, and lumbar surgery. Nevertheless, Medicare and other insurance companies, are now increasingly denying reimbursement (average cost of a “large” INFUSE to the hospital without overhead $5000-6000) to hospitals for INFUSE when utilized “off-label”.
Methods:This commentary looks at several representative studies citing the cons associated with utilizing INFUSE in spinal surgery, contraindications, complications, and cost factors.
Results:There are multiple cons of utilizing INFUSE in an “off-label” capacity for spinal surgery. Direct contraindications include pregnancy, allergy to titanium, allergy to bovine type I collagen or rhBMP-2, infection, tumor, liver or kidney disease, immunosuppression (e.g., lupus, HIV/AIDS); contraindications are also seen in those receiving radiation, chemotherapy, or steroids. Reported complications include exuberant/ectopic bone formation, paralysis (cord, nerve damage), dural tears, bowel–bladder and sexual dysfunction, respiratory failure, inflammation of adjacent tissues, fetal developmental complications, scar, excessive bleeding, and even death. Complications are so prevalent in the anterior cervical spine, that many surgeons no longer use it in this region. Similarly, INFUSE complications and indications for posterior lumbar interbody fusions (PLIFs) and transforaminal interbody lumbar fusions (TLIFs) should also be reexamined.
Conclusions:More surgeons need to question the safety, efficacy, and appropriate “off-label” use of INFUSE in all spine surgeries.
Keywords: INFUSE (rhBMP-2), bone morphogenetic protein, spinal surgery, off-label use
The use of bone morphogenetic protein INFUSE (recombinant human bone morphogenetic protein-2 [rhBMP-2]; Medtronic, Memphis, TN, USA) in cervical, thoracic, and lumbar spine surgery remains controversial. Despite its Federal Drug Administration (FDA) approval solely for anterior lumbar interbody fusions (ALIFs) with a lumbar tapered fusion device (LT Cage; Medtronic), it has been applied at the discretion of individual surgeons in an “off-label” capacity throughout the spine. Surgeons validate its use based upon the “standard of care.” In this review, we examine the cons of utilizing INFUSE, citing its common (e.g., anterior cervical complications) and not-so-commonly known complications, while also taking a cursory look at its pros. Furthermore, several of the studies look at the major financial implications of utilizing INFUSE. Presently, INFUSE costs hospitals an average of $5000-6000 for a large package (actual cost without overhead to the hospital). As Medicare and more insurance companies no longer reimburse or are considering cessation of reimbursement for INFUSE used in an “off-label” capacity (anywhere excluding ALIFs), surgeons may have to turn toward other supplements/alternatives to attain fusion.
Current Status of Approvals for Use of INFUSE
Presently, the FDA has approved INFUSE for use in certain tibial fractures and oral maxillary procedures, along with specific ALIFs with the LT Cage at L2-S1 levels.
Composition of INFUSE
INFUSE consists of two parts. The first is a solution comprised of rhBMP-2 and an absorbable collagen sponge (ACS). The INFUSE protein, a genetically engineered variant, stimulates bone formation. At surgery, the collagen sponge (bovine product consisting of type I collagen which resorbs over time) is impregnated with rhBMP-2, with the latter functioning as a scaffold for new bone formation.
FDA Approval only for ALIF with INFUSE and LT Cage
INFUSE and the LT Cage were originally devised for adult anterior spinal fusions. The combined device is FDA approved for single-level use in the anterior lumbar spine (ALIF) for degenerative disc disease, grade I spondylolisthesis, and/or retrolisthesis at the L2-S1 level. Advantages of this device include avoiding the need for obtaining autograft bone (e.g., iliac crest), shorter surgical procedures (reduced morbidity), and smaller incisions. It may be utilized in patients who have failed, 6 months of conservative, nonsurgical treatment. The surgical procedure may be performed either “open” or minimally invasively (laparoscopic technique).
“Off-Label” Uses of INFUSE
Although INFUSE is FDA approved for use with the LT Cage to perform ALIFs, it is predominantly utilized “off-label” to perform other types of anterior and/or posterior spinal operations. In the cervical spine, it has been utilized to perform anterior (single or multilevel anterior diskectomy/fusion, or anterior corpectomy/fusion) or posterior fusions (fusions with or without laminectomy/decompression). Similarly, anterior and posterior thoracic procedures have utilized INFUSE. The most common “off-label” use is in the posterior lumbar spine where it is utilized to perform posterior lumbar interbody fusions (PLIFs) or transforaminal interbody fusions (TLIFs). INFUSE's utility is predominantly attributed to its ability to enhance fusion rates, decrease the length of some surgeries, and potentially decrease the length of hospital stay. Nevertheless, more data are needed to allow for a more careful consideration of the pros and cons of utilizing INFUSE.
Contraindications for INFUSE
There are multiple contraindications associated with utilizing INFUSE and the LT Cage. Contraindications include pregnancy or in someone who will become pregnant, a history of sensitivity to titanium alloy, allergy to bovine type I collagen, or recombinant human rhBMP-2, infection, tumor, or where bones are not mature (still growing). It is also contraindicated in patients with liver or kidney disease, in those with osteoporosis or metabolic bone disorders, in immunosuppressed patients including those with autoimmune disease (e.g., Lupus, HIV/AIDS), and in those receiving radiation, chemotherapy, or steroids.
Summary of Complications Reported with INFUSE/LT Cage
There are multiple complications reported in conjunction with the application of INFUSE and the LT Cage. Complications include exuberant bone formation at the site of implantation or ectopic bone formation at the site of original insertion/application. Other complications include bending, breakage, loosening, and/or migration of the implant, failure to fuse, paralysis and/or other neurological complications (spinal cord, nerve damage), dural tears, bowel, bladder, and sexual dysfunction, respiratory failure, gastrointestinal problems, damage to adjacent tissues (inflammatory response/swelling), death, fetal developmental complications, scar formation, bleeding which may warrant transfusions, and vascular problems excluding bleeding,
Cons for INFUSE in Cervical Spine Surgery: A Literature Review
The increased risks associated with utilizing INFUSE for anterior cervical spine surgeries are well publicized. One study systemically assessed 240 articles written between 1990 and 2009 on utilizing INFUSE for cervical, thoracic, and lumber surgery; only 31 were adequate for inclusion.[
In another retrospective anterior cervical study, 35 (23.2%) of 151 patients undergoing anterior diskectomy and fusion (138) or anterior corpectomy and fusion (13) developed complications attributed to INFUSE (2003-2004).[
One case study reported postoperative neurological deterioration attributed to a massive seroma (severe inflammatory response) attributed to INFUSE utilized to perform a posterior occipital/cervical fusion.[
Cons for INFUSE in Lumbar Spine Surgery
The “off-label” use of INFUSE for lumbar surgery is the most prevalent (compared with cervical or thoracic surgery), and complications (cons) occurring following PLIF and TLIF procedures have become more recognizable. A review of multiple articles regarding the use of INFUSE in the lumbar spine revealed that its “off-label” use with the interbody cage contributed to a 44% resorption rate, a 25% subsidence rate, and a 27% incidence of cage migration.[
PROS of INFUSE Lumbar Fusions
Multiple reports cite the attributes (pros) of utilizing INFUSE to perform spinal surgery. A prospective, non-blinded, multicenter study involved 46 patients undergoing single-level anterior lumbar diskectomy and interbody fusion with INFUSE (ALIF) utilizing allograft bone dowels (other studies used the LT Cages).[
Costs of INFUSE
Two studies have documented the cost-effectiveness of INFUSE in spinal surgery. In the first, a prospective randomized trial assessed the relative cost-effectiveness and efficacy of INFUSE bone graft (rhBMP-2/ACS: 50 patients) versus ICBG in 52 patients for lumbar fusions in patients over the age of 60.[
Medicare and other insurers are increasingly not reimbursing institutions for the “off-label” use of INFUSE in spine surgery. Where, when, and how INFUSE is utilized in the future will have to depend on a reexamination of the indications, efficacy, and safety of its use, and its cost to the hospital, typically $5000-6000 (without overhead).
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