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Background
Chronic rhino-sinusitis (CRS) is defined as an inflammatory condition involving the para-nasal sinuses and linings of the nasal passages that lasts 12 weeks or longer, despite attempts at medical management. It is one of the most frequently diagnosed chronic medical conditions, affect patients of all ages and gender. Treatments of CRS include saline washes and sprays, topical and systemic glucocorticoids, antibiotics, anti-leukotriene agents, as well as anti-fungals. Surgery should be the last resort in most cases of CRS. Endoscopic sinus surgery (ESS) is the most commonly used surgical intervention to treat medically unresponsive CRS. It is intended to restore physiologic sinus ventilation and drainage (Hamilos, 2012). While ESS has become a well-established strategy for the treatment of CRS that is refractory to medical treatment, it is associated with various complications. The incidence of major complications of ESS was estimated to be 1 to 3 %, with cerebrospinal fluid leak being the most common; and the incidence of minor complications was approximately 7.0 %, with middle meatal (MM) synechiae being the most common (May et al, 1994; Ramakrishnan et al, 2012).
Implantable sinus stents/spacers have been used following ESS to maintain patency of the sinuses and deliver local steroids. The Stratus MicroFlow Spacer is designed to provide slow release of steroids into the sinuses over a 2-week period with the intention of maintaining sinus ostial patency. This device may be used in either the frontal or ethmoid sinuses. Propel™ is a steroid-releasing sinus implant that is inserted into the ethmoid sinus. It is indicated for maintaining sinus patency after ESS in patients 18 years of age and older. This steroid releasing implant is comprised of a synthetic bioabsorbable co-polymer and is self-expanding, which allows it to conform to the highly variable contours and size of the sinus anatomy. Propel™ is inserted into the ethmoid sinus cavity by a physician under endoscopic visualization. Upon insertion, the implant expands radially to conform to the sinus cavity. The delivery system is then removed and discarded. Once Propel™ is in place, mometasome furoate is released over a 30-day period. Dosages for Propel™ are measured in terms of the number of implants inserted in a patient's sinus cavities. Each steroid-releasing implant contains 370 micrograms of mometasome furoate.
Catalano et al (2011) evaluated the safety and short-term outcomes of a newly introduced drug-eluting ethmoid stent (the MicroFlow Spacer) in 23 patients with a total of 40 implanted ethmoid sinuses. Patients with medically refractory CRS were treated with patient-appropriate ESS, with the modification of treating the ethmoid sinuses with an ethmoid stent infused with triamcinolone, instead of conventional endoscopic ethmoidectomy. Patients were then followed-up over 6 months. Safety was determined by adverse events. Outcomes were assessed by interval changes in 20-item Sino-Nasal Outcome Test (SNOT-20) and Lund-MacKay CT scores. Overall, the pre-operative SNOT-20 mean score was 2.18, versus post-operative score of 1.02, an improvement of 1.16 that was both statistically (p < 0.001) and clinically significant. Ethmoid-specific and side-specific Lund-MacKay mean scores both also showed statistically significant improvements. Pre-operative ethmoid-specific Lund-MacKay mean score was 1.93, versus post-operative score of 1.10, an improvement of 0.83 (p < 0.001). Pre-operative side-specific Lund-MacKay mean score was 5.75, compared with post-operative score of 2.95, an improvement of 2.80 (p < 0.001). There were no significant intra-operative or post-operative complications encountered. The authors concluded that the MicroFlow spacer appears safe and effective in treating chronic ethmoid sinus disease within the defined follow-up period. They noted that the ability to deliver medication directly to diseased mucosa holds wide-ranging potential. The findings of this small study need to be validated by well-designed studies with long-term follow-up.
In a prospective, multi-center, single-cohort trial (Advance Trial), Forwith et al (2011) evaluated the safety and effectiveness of a bioabsorbable, steroid-eluting implant (the Propel™ device) used following ESS in patients with CRS (n = 50). The study allowed bilateral or unilateral steroid-eluting implant placement. Oral and topical steroids were withheld for 60 days post-operatively. Endoscopic follow-up was performed to 60 days. Patient-reported outcomes (SNOT-22 Questionnaire, Rhinosinusitis Disability Index) were collected to 6 months. Efficacy was assessed by grading inflammation, polyp formation, adhesions, and middle turbinate position. Safety assessment included ocular examinations at baseline and 30 days. Implants were successfully placed in all 90 sinuses. Mean inflammation scores were minimal at all time-points. At 1 month, the prevalence of polypoid edema was 10.0 %, significant adhesions 1.1 %, and middle turbinate lateralization 4.4 %. Changes from baseline in patient-reported outcomes were statistically significant (p < 0.0001). No clinically significant changes from baseline in intra-ocular pressure (IOP) occurred. The authors concluded that this consecutive case-series study provided clinical evidence of the safety, effectiveness, and clinical utility of a bioabsorbable steroid-eluting implant for use in CRS patients. The implant was associated with favorable rates of sinus patency. At 1 month, minimal degrees of inflammation and adhesions were observed, suggesting a positive clinical impact of local steroid delivery without evidence of ocular risks.
In a prospective, multi-center, randomized, controlled, double-blind trial (Advance II Trial), Marple et al (2012) examined the safety and effectiveness of controlled delivery of mometasone furoate to the sinus mucosa via the Propel™ sinus implant deployed at the time of ESS. This study enrolled 105 patients with CRS undergoing bilateral ethmoidectomy to compare the effect of drug-releasing to non-drug-releasing implants using an intra-patient control design. Post-operative interventions, polyposis, and adhesions were assessed post-operatively. Efficacy was determined through independent analysis of randomized video-endoscopies by 3 blinded sinus surgeons. Safety assessments included ocular examinations. Implants were successfully deployed in all 210 ethmoid sinuses. Compared with control sinuses with non-drug-releasing implants, the drug-releasing implant provided a 29.0 % relative reduction in post-operative interventions (p = 0.028) and a 52 % (p = 0.005) decrease in lysis of adhesions. The relative reduction in frank polyposis was 44.9 % (p = 0.002). Similar reductions were observed in real-time grading performed by the clinical investigators. No clinically significant changes from baseline in IOP or cataracts were observed. The authors concluded that this study provided evidence that use of the Propel™ sinus implant that applies a sustained release of corticosteroid improves surgical outcomes by reducing synechiae formation, polyposis, and the need for post-operative interventions, with no observable ocular safety risk.
While the results of the two Advance Trials are promising, they were limited to small, heterogeneous populations with short-term follow-up. Furthermore, the trials were performed in a setting where both sinuses had implants, one with steroid and the other without. The two trials discussed above did not compare the post-operative outcomes using this device with outcomes following standard ESS without an ostial implant but with topical steroid sprays, saline irrigation, debridement, and conventional post-operative packing. The available evidence is insufficient to determine whether sinus spacers and stents improve outcomes when used post-operatively following ESS. Further randomized controlled trials (RCTs) are needed to compare the Propel™ device to optimal post-operative care without the device to determine whether it can improve post-operative outcomes for patients undergoing ESS.
In a randomized, double-blind, placebo-controlled trial, Rudmik et al (2012) evaluated a dexamethasone Sinu-Foam™ spacer following ESS for CRS without nasal polyposis (CRSsNP). Patients with CRSsNP (n = 36) were enrolled into a double-blind, placebo-controlled trial and randomized into either a treatment arm (dexamethasone Sinu-Foam™ mixture; n = 18) or placebo arm (Sinu-Foam™ alone; n = 18). Therapeutic outcomes were evaluated at 1 week, 4 weeks, and 3 months using sino-nasal endoscopy and graded using the Lund-Kennedy scoring system. Post-operative care included nasal saline irrigations and a short course of systemic steroids. All patients completed the study follow-up period. Both study arms experienced significant improvement in endoscopic grading over the study duration (p < 0.001). There was no difference in average endoscopic scores between the treatment and placebo groups at 1 week, 4 weeks, and 3 months (all p > 0.489). The authors concluded that the findings of this study demonstrated that an off-label drug-eluting MM spacer of dexamethasone and Sinu-Foam™ does not improve endoscopic outcomes in the early post-operative period following ESS when combined with post-operative saline irrigations and a short course of systemic steroids.
Weitzel and Wormald (2008) performed a literature review to identify all forms of scientifically evaluated absorbable packing for ESS. Only English studies identifiable within the PubMed database were included. Studies were categorized by level of evidence and evaluated for methodological errors. A total of 38 studies met the inclusion criteria. There was a diverse range of article evidence and quality. The most effective hemostatic agent currently available is FloSeal; however, this product causes an increase in adhesion formation. For the purpose of preventing adhesions, resorbable packs appear to have no benefit over either non-resorbables or no packing. If the middle turbinate is unstable at the conclusion of surgery, suturing it to the septum may reduce adhesions. Although mitomycin C, hyaluronic acid, and retinoic acid all have shown potential in these roles, to date, none has shown to be useful in post-ESS CRS patients.
In a systematic review and meta-analysis, Lee and Grewal (2012) examined if MM spacers actually reduce the risk of synechiae following ESS. The Preferred Reporting of Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines was used for reporting this review of RCT evaluating the effectiveness of MM spacers compared to no spacers in patients undergoing ESS. Where appropriate, a meta-analysis on outcome data using a random effects model was performed. A total of 8 RCTs were included in this systematic review. A pooled analysis on relevant trials found a non-significant trend favoring MM spacers compared to no spacers for the prevention of synechiae following ESS (relative risk [RR], 0.40; 95 % confidence interval [CI]: 0.14 to 1.12). Sub-group analysis suggested that non-absorbable spacers (NAS) may be more effective than absorbable spacers (AS) for reducing the risk of synechiae compared to no spacers. The authors concluded that MM spacers may be more effective than no spacers for the prevention of synechiae following ESS, especially when employing the use of an NAS. However, the authors noted that significant heterogeneity was observed among included trials and future studies are needed to further validate these findings.
In summary, a variety of implants/spacers (e.g., the Propel™ sinus implant, the Relieva Stratus™ MicroFlow spacer, and the Sinu-Foam™ spacer) have been employed to maintain patency of the sinuses and deliver local steroids with varying success in the reported literature. However, the available studies have significant heterogeneity in this outcome. There remains a continued debate on whether these devices actually improve the health outcomes following ESS.
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