Dysphagia consists one of the most disturbing post-operative symptoms, with reported incidence varying from 1% to approximately 80% of patients undergoing anterior cervical procedures (1). It is also known that despite the high reported rates of early postoperative dysphagia, it has been demonstrated that less than 15% of the patients will finally experience dysphagia one year after surgery (2). Generally, dysphagia is characterized as difficulty in the swallowing process, and it may affect the consumption of both solid food and/or liquids. Many factors have been implicated in the genesis of postoperative dysphagia, such as previous neck surgery, prolonged operative time, multi-level procedure, excessive intraoperative esophageal retraction, employment of rhBMP-2, implantation of anterior cervical plate, and postoperative development of prevertebral soft tissue edema.
Indeed, the role of the human bone morphogenetic proteins, such as rhBMP-2, in the emergence of dysphagia has been adequately documented in the literature. Tannoury et al. in their literature review evaluating the adverse events and complications associated with the use of rhBMP-2 in spinal procedures, identified the implication of rhBMP-2 in the development of postoperative neck soft tissue swelling and dysphagia (3). Smucker et al. in their study demonstrated the association of rhBMP-2 in the postoperative development of prevertebral soft tissue edema in anterior cervical procedures with fusion (4). Similarly, Vaidya et al. showed that rhBMP-2 was associated with dysphagia, and increased incidence of postoperative soft tissue swelling (5). Mroz et al., in their systematic review regarding the side effects of BMPs in spine fusion surgery, identified dysphagia as one of the most important side effects (6). Fu et al. concluded that rhBMP-2 was strongly associated with dysphagia development in anterior cervical procedures (7). Likewise, Burkus et al. reached the conclusion that dysphagia was significantly higher among patients receiving BMP (8). Lu et al. reported that although the overall incidence of dysphagia was not affected by the employment of rhBMP-2, its severity was associated with the usage of rhBMP-2, in their study (9).
The well documented effect of BMP in facilitating osseous fusion led to the employment of lower doses, in an effort to decrease the incidence of the associated soft tissue swelling and dysphagia. Stachniak et al. reported that only 6.7% of their patients had persistent dysphagia with low dose rhBMP-2, 6 months after their procedure (10). Similarly, Kukreja et al. reported lower incidence of postoperative dysphagia with lower rhBMP-2 doses (11). Pourtaheri et al. studied the safety and efficacy of a minimum rhBMP-2 dose in three-level ACDF procedures (12). They concluded that the rates of dysphagia in their patients were similar with those of series using no rhBMP-2 (12). Khajavi et al. reported similar results by using low-dose rhBMP-2 in multi-level ACDFs (13). Tumialán et al. also reported lower incidence of dysphagia with low dose rhBMP-2 in single- and multi-level ACDFs, in their cohort (14). In a recent meta-analysis study, it was demonstrated that a low dose of BMP (0.2–0.6 mg/level) might significantly improve the fusion rates without increasing the incidence of postoperative dysphagia (15).
Steroids have been used in the past for minimizing the incidence of postoperative dysphagia in patients undergoing ACDFs (16). Lee et al. reported decreased postoperative dysphagia and prevertebral soft tissue swelling among patients undergoing ACDFs after applying steroids in the retropharyngeal space (17). They also found that this effect was maintained for at least the first four weeks postoperatively (17). However, the same group of researchers reported delayed esophageal perforation, as a significant adverse event occurring after the local administration of steroids in the retropharyngeal space (18). Koreckij et al., reported their experience from locally applying a saturated collagen sponge with methylprednisolone, in patients undergoing multi-level ACDFs (19). They found that dysphagia was significantly lower among patients receiving steroids, compared to those with no steroids, at six and twelve weeks after surgery. Interestingly, the incidence of postoperative prevertebral soft tissue swelling was reduced immediately after surgery in the steroid group, but showed no difference between the steroid and the placebo groups 12 weeks after surgery (19).
It may be hypothesized that the increased incidence of dysphagia may be associated with the inflammatory effect of BMP, thus local application of steroids could decrease the incidence of dysphagia. Edwards et al., in their current prospective, randomized, double-blinded study employed depomedrol-saturated sponge at the surgical site (ventrally to the implanted anterior plate), while they used a low-dose rhBMP-2 (0.5 mg/level), in order to mitigate the side effect of postoperative dysphagia, and to maintain the rhBMP-2 effect of facilitating the osseous fusion (20). They reported statistically significant decrease in the incidence of dysphagia among the patients receiving steroids compared to the placebo group, who received just saline (20). They also demonstrated that this effect was maintained for at least four weeks postoperatively (20). Although their findings are statistically powerful, the limited number of participants in their cohort makes the performance of a large-scale, prospective study absolutely necessary for confirming their promising results. The long-term effect of steroids in preventing dysphagia should also be assessed in a future study. Moreover, the occurrence of any steroid-associated side effects or complications (increased infection rate, esophageal perforation, surgical wound healing) should be excluded.
Conflicts of Interest: The authors have no conflicts of interest to declare.
Comment on: Edwards CC 2nd, Dean C, Edwards CC, et al. Can Dysphagia Following Anterior Cervical Fusions With rhBMP-2 Be Reduced With Local Depomedrol Application?: A Prospective, Randomized, Placebo-Controlled, Double-Blind Trial. Spine (Phila Pa 1976) 2016;41:555-62.
- Anderson KK, Arnold PM. Oropharyngeal Dysphagia after anterior cervical spine surgery: a review. Global Spine J 2013;3:273-86. [Crossref] [PubMed]
- Cho SK, Lu Y, Lee DH. Dysphagia following anterior cervical spinal surgery: a systematic review. Bone Joint J 2013;95-B:868-73. [Crossref] [PubMed]
- Tannoury CA, An HS. Complications with the use of bone morphogenetic protein 2 (BMP-2) in spine surgery. Spine J 2014;14:552-9. [Crossref] [PubMed]
- Smucker JD, Rhee JM, Singh K, et al. Increased swelling complications associated with off-label usage of rhBMP-2 in the anterior cervical spine. Spine (Phila Pa 1976) 2006;31:2813-9. [Crossref] [PubMed]
- Vaidya R, Carp J, Sethi A, et al. Complications of anterior cervical discectomy and fusion using recombinant human bone morphogenetic protein-2. Eur Spine J 2007;16:1257-65. [Crossref] [PubMed]
- Mroz TE, Wang JC, Hashimoto R, et al. Complications related to osteobiologics use in spine surgery: a systematic review. Spine (Phila Pa 1976) 2010;35:S86-104. [Crossref] [PubMed]
- Fu R, Selph S, McDonagh M, et al. Effectiveness and harms of recombinant human bone morphogenetic protein-2 in spine fusion: a systematic review and meta-analysis. Ann Intern Med 2013;158:890-902. [Crossref] [PubMed]
- Burkus JK, Dryer RF, Arnold PM, et al. Clinical and Radiographic Outcomes in Patients Undergoing Single-level Anterior Cervical Arthrodesis: A Prospective Trial Comparing Allograft to a Reduced Dose of rhBMP-2. Clin Spine Surg 2016. [Epub ahead of print].
- Lu DC, Tumialán LM, Chou D. Multilevel anterior cervical discectomy and fusion with and without rhBMP-2: a comparison of dysphagia rates and outcomes in 150 patients. J Neurosurg Spine 2013;18:43-9. [Crossref] [PubMed]
- Stachniak JB, Diebner JD, Brunk ES, et al. Analysis of prevertebral soft-tissue swelling and dysphagia in multilevel anterior cervical discectomy and fusion with recombinant human bone morphogenetic protein-2 in patients at risk for pseudarthrosis. J Neurosurg Spine 2011;14:244-9. [Crossref] [PubMed]
- Kukreja S, Ahmed OI, Haydel J, et al. Complications of Anterior Cervical Fusion using a Low-dose Recombinant Human Bone Morphogenetic Protein-2. Korean J Spine 2015;12:68-74. [Crossref] [PubMed]
- Pourtaheri S, Hwang K, Faloon M, et al. Ultra-low-dose recombinant human bone morphogenetic protein-2 for 3-level anterior cervical diskectomy and fusion. Orthopedics 2015;38:241-5. [Crossref] [PubMed]
- Khajavi K, Shen A. Safety and efficacy of bioabsorbable cervical spacers and low-dose rhBMP-2 in multi-level ACDF. Int J Spine Surg 2014;8.
- Tumialán LM, Pan J, Rodts GE, et al. The safety and efficacy of anterior cervical discectomy and fusion with polyetheretherketone spacer and recombinant human bone morphogenetic protein-2: a review of 200 patients. J Neurosurg Spine 2008;8:529-35. [Crossref] [PubMed]
- Hofstetter CP, Hofer AS, Levi AD. Exploratory meta-analysis on dose-related efficacy and morbidity of bone morphogenetic protein in spinal arthrodesis surgery. J Neurosurg Spine 2016;24:457-75. [Crossref] [PubMed]
- Siasios I, Fountas K, Dimopoulos V, et al. The role of steroid administration in the management of dysphagia in anterior cervical procedures. Neurosurg Rev 2016. [Epub ahead of print]. [Crossref] [PubMed]
- Lee SH, Kim KT, Suk KS, et al. Effect of retropharyngeal steroid on prevertebral soft tissue swelling following anterior cervical discectomy and fusion: a prospective, randomized study. Spine (Phila Pa 1976) 2011;36:2286-92. [Crossref] [PubMed]
- Lee SH, Mesfin A, Riew KD. Delayed esophageal perforation after anterior cervical fusion and retropharyngeal steroid use: a report of two cases. Spine J 2015;15:e75-80. [Crossref] [PubMed]
- Koreckij TD, Davidson AA, Baker KC, et al. Retropharyngeal Steroids and Dysphagia Following Multilevel Anterior Cervical Surgery. Spine (Phila Pa 1976) 2016;41:E530-4. [Crossref] [PubMed]
- Edwards CC 2nd, Dean C, Edwards CC, et al. Can Dysphagia Following Anterior Cervical Fusions With rhBMP-2 Be Reduced With Local Depomedrol Application?: A Prospective, Randomized, Placebo-Controlled, Double-Blind Trial. Spine (Phila Pa 1976) 2016;41:555-62. [Crossref] [PubMed]