Otolaryngology http://oto.sagepub.com/ -- Head and Neck Surgery
The Role of Immediate Postoperative Systemic Corticosteroids When Utilizing a Steroid-eluting Spacer Following Sinus Surgery Jon F. Dautremont, Brad Mechor and Luke Rudmik Otolaryngology -- Head and Neck Surgery 2014 150: 689 originally published online 30 January 2014 DOI: 10.1177/0194599814521373 The online version of this article can be found at: http://oto.sagepub.com/content/150/4/689
Published by: http://www.sagepublications.com
On behalf of:
American Academy of Otolaryngology- Head and Neck Surgery
Additional services and information for Otolaryngology -- Head and Neck Surgery can be found at: Email Alerts: http://oto.sagepub.com/cgi/alerts Subscriptions: http://oto.sagepub.com/subscriptions Reprints: http://www.sagepub.com/journalsReprints.nav Permissions: http://www.sagepub.com/journalsPermissions.nav
>> Version of Record - Apr 1, 2014 OnlineFirst Version of Record - Jan 30, 2014 What is This?
Downloaded from oto.sagepub.com at UNIV TORONTO on August 10, 2014
Original Research—Sinonasal Disorders
The Role of Immediate Postoperative Systemic Corticosteroids When Utilizing a Steroid-eluting Spacer Following Sinus Surgery
Otolaryngology– Head and Neck Surgery 2014, Vol. 150(4) 689–695 Ó American Academy of Otolaryngology—Head and Neck Surgery Foundation 2014 Reprints and permission: sagepub.com/journalsPermissions.nav DOI: 10.1177/0194599814521373 http://otojournal.org
Jon F. Dautremont, MD1, Brad Mechor, MD1, and Luke Rudmik, MD, MSc1
No sponsorships or competing interests have been disclosed for this article.
Keywords
Abstract
chronic rhinosinusitis, sinusitis, topical steroid, middle meatal spacer, sinus surgery, corticosteroid
Objective. Steroid-eluting spacers can improve local drug delivery immediately following endoscopic sinus surgery and reduce the recurrence of inflammation warranting systemic corticosteroids. For chronic rhinosinusitis with nasal polyposis, the need for systemic corticosteroids immediately following endoscopic sinus surgery when using a steroideluting spacer has not been studied. Study Design. A randomized, double-blind, placebo-controlled trial. Setting. Academic rhinology practice. Subjects and Methods. Chronic rhinosinusitis patients with nasal polyposis who failed medical therapy and elected endoscopic sinus surgery were enrolled. Patients were randomized into either the treatment arm (postoperative prednisone 30 mg daily 3 7 days; n = 18) or placebo arm (postoperative placebo pill daily 3 7 days; n = 18). Outcomes were evaluated at 1 week, 3 weeks, and 2 months postoperatively. Primary outcome was endoscopic grading at postoperative month 2 using the Lund–Kennedy system. Secondary outcome included disease-specific quality of life using the Sinonasal Outcome Test (SNOT-22) survey. Patient enrolment occurred from January 2012 through February 2013 (NCT01564355). Results. Both arms received significant improvement in endoscopic grading and disease-specific quality of life from baseline compared to 2-month follow-up (P \.001). There were no significant differences in mean endoscopic scores between the postoperative prednisone and control groups at 1 week (P = .715), 3 weeks (P = .883), or 2 months (P = .343). There were no significant differences in SNOT-22 scores between groups at all follow-up points (all P . .119). Conclusion. Minimizing systemic corticosteroid use in patients with chronic rhinosinusitis with nasal polyposis may avoid adverse events. Results from this study suggest that postoperative systemic corticosteroids immediately following endoscopic sinus surgery may not provide improved outcomes when utilizing a steroid-eluting spacer.
Received October 24, 2013; revised December 17, 2013; accepted January 7, 2014.
Introduction Endoscopic sinus surgery (ESS) is an excellent management option for patients with medically refractory chronic rhinosinusitis (CRS).1-6 An important goal in the early postoperative period is to minimize mucosal inflammation, promote normal ciliary function, and reduce the risk of complications such as synechiae and infection.7 To minimize postoperative mucosal inflammation, most experts would recommend high volume saline irrigations and early topical corticosteroid therapy.7 However, the early postoperative milieu of sinonasal crusting, retained secretions, and edema significantly impair adequate delivery of topical corticosteroid therapy immediately following ESS. To overcome this challenge, surgeons often consider providing a short course of postoperative systemic corticosteroids, which has been shown to significantly improve postoperative endoscopic outcomes in CRS patients with nasal polyposis.8 Although effective, the use of systemic corticosteroids has potential serious adverse effects and identifying strategies to reduce these risks while maintaining the clinical benefit would improve patient care.9-11 1
Division of Otolaryngology–Head and Neck Surgery, Department of Surgery, University of Calgary, Calgary, Alberta, Canada This article was presented at the 2013 AAO-HNSF Annual Meeting & OTO EXPO; September 29-October 3, 2013; Vancouver, British Columbia, Canada. Corresponding Author: Luke Rudmik, Division of Otolaryngology–Head and Neck Surgery, Department of Surgery, University of Calgary, Foothills Medical Centre, South Tower, Ste 602, 1403 29th St NW, T2N 2T9, Calgary, Alberta, Canada. Email: [email protected]
Downloaded from oto.sagepub.com at UNIV TORONTO on August 10, 2014
690
Otolaryngology–Head and Neck Surgery 150(4)
Drug eluting middle meatal spacers have been developed to deliver topical corticosteroid therapy without the need for spray, drop, or irrigation delivery techniques.12-15 In the early postoperative period following ESS, the use of drugeluting spacers has gained popularity since they can deliver topical corticosteroid to the sinonasal mucosa during a time when the traditional techniques of sprays and irrigations often fail due to impaired access from crusting and edema. Bioabsorbable steroid-eluting stents have also been shown to reduce the recurrence of sinonasal inflammation that would warrant systemic corticosteroid treatment, in the late postoperative period.16 Since drug-eluting spacers improve topical corticosteroid therapy in the immediate postoperative period, concurrent early postoperative systemic corticosteroid therapy may not be required. The purpose of this study is to evaluate the effectiveness of immediate postoperative systemic corticosteroid therapy when utilizing a middle meatal steroid-eluting spacer in CRS patients with nasal polyposis following ESS. The primary outcome was endoscopic grading and the secondary outcome was disease-specific quality of life (QoL). We hypothesized that continuing postoperative systemic corticosteroids would further improve endoscopic grading when utilizing a middle meatal steroid-eluting spacer following ESS for refractory CRS with nasal polyposis.
Methods and Materials Study Design This study is a randomized, double-blind, placebo-controlled trial (NCT01564355). Patients were enrolled between January 2012 and February 2013. Inclusion criteria included adults over 18 years of age, a diagnosis of CRS with nasal polyposis according to the 2007 Adult Sinusitis Guidelines,17 and elected ESS for an indication of refractory CRS. Refractory CRS was defined as persistent symptoms despite a minimum of 3 months topical corticosteroid spray or irrigations, minimum of a 2-week course of systemic corticosteroid (prednisone 30 mg PO once daily) and a minimum 2-week course of broad-spectrum antibiotic in the presence of mucopurulence. Exclusion criteria included patients with suspected systemic inflammatory disease, cystic fibrosis, and any contraindication to systemic corticosteroids.18 Patients undergoing concurrent septoplasty were not excluded as it has not been shown to be a confounding variable.19 Study protocol was approved by the University of Calgary Conjoint Health Research Ethics Board (Ethics ID: 24336), and informed consent was obtained from each study participant. Patients were randomized into either the intervention or placebo group (Figure 1). Patients in the intervention group received postoperative prednisone therapy (30 mg once daily 3 7 days) beginning 1 day after ESS. Patients in the control group received a postoperative placebo (once daily 3 7 days) beginning 1 day after ESS. Randomization was performed using a computer generated block-randomization allocation. The block size was 6. The enrolling surgeons (LR and BM) were blinded to the assigned group.
Preoperative Management In preparation for ESS, all enrolled patients received the same preoperative medications which included 7 days of oral prednisone (30 mg once daily) and 7 days of oral antibiotic. Antibiotic choice was either amoxicillin/clavulanate 875 mg twice daily, trimethoprim/sulfmethoxazole 160/800 mg twice daily (if penicillin allergy) or clarithromycin 500 mg twice daily (if penicillin and sulfa allergy).
Intraoperative Management All patients underwent ESS which included bilateral maxillary antrostomy, total ethmoidectomy, sphenoidotomy, and frontal sinusotomy. The surgeons were blinded to patient randomization. All patients had 1 Nasoporeä dissolvable spacer soaked with 2 ml of triamcinolone (40 mg/ml) placed into each of the ethmoid cavities at the completion of the ESS procedure.15 Nasopore is a co-polyetherester urethane foam that fragments within several days in the nasal cavity. Its high absorbency makes it useful as a carrier for fluid substances, as it can hold up to 25 times its weight in topical medication.
Postoperative Management Postoperative care followed appropriate evidence based recommendations and included the following protocol: high volume nasal saline irrigations (using a Neilmedä saline sinus rinse bottle) 3 times per day starting 1 day after ESS, continuing the systemic antibiotic for 7 days after ESS, and an endoscopic debridement at 1 and 3 weeks postoperatively.7 Topical nasal corticosteroid therapy was initiated at the 1 week postoperative visit. Topical steroid therapy following the debridement consisted of high volume budesonide irrigation once daily (1 mg in 240 ml of saline). This was initiated after the patient underwent their first nasal cavity debridement, which allowed for the effective delivery of topical steroid solution into the sinonasal cavity.
Data Collection Upon patient enrollment, baseline demographic information and preoperative Lund–Mackay computed tomography (CT) score were recorded. The primary outcome was endoscopic grading at postoperative month 2, which was collected using the validated 20-point Lund–Kennedy endoscopic scoring system, which assesses patients on the presence of polyps, edema, discharge, scarring, and crusting.20 The secondary outcome was disease-specific QoL at postoperative month 2, which was collected using the validated 22-item Sinonasal Outcome Test (SNOT-22) questionnaire.21 Data were collected in 2 tertiary rhinology clinics at 1 week, 3 weeks, and 2 months postoperatively. The surgeons were blinded to patient randomization throughout this period.
Statistical Analysis and Sample Size Calculation Completed survey data and scoring scales were collected, transcribed, and manually entered into a database by a trained study coordinator using standardized clinical research forms. Data were deidentified and securely stored during the data collection period (Microsoft Excel; Microsoft Corp, Redmond,
Downloaded from oto.sagepub.com at UNIV TORONTO on August 10, 2014
Dautremont et al
691 Assessed for eligibility (n=36)
Excluded (n=0)
Randomized (n=36)
Allocated to post-operative prednisone group (n=18) • Received prednisone (n=18) • Did not receive prednisone (n=18)
Allocated to post-operative placebo group (n=18) • Received placebo (n=18) • Did not receive placebo (n=18)
Pre-operative therapy (n=18) • Oral antibiotics x 7 days • Prednisone 30 mg daily x 7 days • Topical steroid rinse/spray
Pre-operative therapy (n=18) • Oral antibiotics x 7 days • Prednisone 30 mg daily x 7 days • Topical steroid rinse/spray
Surgery (n=18) • Minimum maxillary antrostomy, total ethmoidectomy • NasoporeTM spacer with 2 mL of 40 mg/mL triamcinolone
Surgery (n=18) • Minimum maxillary antrostomy, total ethmoidectomy • NasoporeTM spacer with 2 mL of 40 mg/mL triamcinolone
Post-operative therapy (n=18) • Oral antibiotics x 7 days • Prednisone 30 mg daily x 7 days • Nasal saline rinse starting POD #1 • Budesonide nasal rinse starting at week 1 • Debridement at 1 & 3 weeks
Post-operative therapy (n=18) • Oral antibiotics x 7 days • Placebo daily x 7 days • Nasal saline rinse starting POD #1 • Budesonide nasal rinse starting at week 1 • Debridement at 1 & 3 weeks
Lost to follow-up (n=0)
Lost to follow-up (n=0)
Analyzed (n=18) • Evaluation at 1-week, 3weeks, and 2-months postoperatively
Analyzed (n=18) • Evaluation at 1-week, 3weeks, and 2-months postoperatively
Figure 1. Randomized controlled trial study design and patient flow diagram.
Washington). All statistical analysis was performed using commercially available software (Stata 12.1; StataCorp LP, College Station, Texas). Descriptive statistics were provided for patient demographics including means and frequencies. For the primary and secondary outcomes, differences between the prednisone and placebo groups at 1 week, 3 weeks, and 2 months were analyzed using a 2-sided Student’s t test. Differences between groups from baseline to 2 months postoperatively were analyzed using a paired t test. P \ .05 was considered a statistically significant difference.
Based on the data published from the study by Wright et al we assumed a 25% improvement in mean Lund–Kennedy score.8 Using a 2-sample comparison of proportions with a power of 90% and an alpha of 5%, we calculated a sample size of 36 required, 18 in each treatment arm.
Results A total of 36 patients were enrolled. Eighteen patients were randomized into each group: (1) postoperative prednisone group and (2) postoperative placebo group. None of the
Downloaded from oto.sagepub.com at UNIV TORONTO on August 10, 2014
692
Otolaryngology–Head and Neck Surgery 150(4)
Table 1. Baseline Demographic and CRS Severity Comparisons between Prednisone and Placebo Groups. Characteristic
Prednisone group (n = 18)a
Placebo group (n = 18)a
P value
46.4 45 (8) 56 (10) 39 (7) 11 (2) 0 (0) 16.3 8.5 47.8
41.7 56 (10) 56 (10) 33 (6) 6 (1) 0 (0) 15.8 8.9 42.2
.411 .444 1.0 .120 .364 1.0 .696 .579 .355
Age, mean years Male gender, n Asthma, n Allergy, n ASA intolerance Smoker Lund–Mackay CT review (mean) Lund–Kennedy endoscopic appearance (mean) SNOT-22 (mean)
Abbreviations: ASA, acetylsalicyclic acid; CRS, chronic rhinosinusitis; CT, computed tomography; SNOT-22, Sinonasal Outcome Test. a Values are percentages with n values in parentheses, unless otherwise noted.
Table 2. Comparison of Baseline and Postoperative Outcomes When Utilizing a Middle Meatal Steroid-eluting Spacer.
Prednisone group Placebo group
Outcome
Baseline (mean 6 SD)
Month 2 postoperative (mean 6 SD)
Endoscopy grade SNOT-22 Endoscopy grade SNOT-22
8.5 6 2.1 47.8 6 18.2 8.9 6 2.6 42.2 6 18.1
2.2 6 1.6 11.5 6 7.3 1.7 6 1.5 10.4 6 10.1
Mean absolute difference 6 SD 6.2 36.4 7.2 31.8
6 2.3 6 20.3 6 3.1 6 18.7
P value \.001 \.001 \.001 \.001
Abbreviation: SNOT-22, Sinonasal Outcome Test.
patients were lost to follow-up. All patients in each group fully completed the assigned postoperative medical therapy and standardized postoperative care protocols. No patient discontinued therapy due to any reported adverse effect. As seen in Table 1, both patient groups were similar in terms of demographics and presence of CRS-related comorbid diseases (all P . .12). There were no significant differences between patient groups in any of the preoperative measures of disease severity, including Lund–Mackay CT scoring (P = .696), Lund–Kennedy endoscopic grading (P = .579), and SNOT-22 (P = .355). When comparing baseline scores to the final 2-month outcomes, both groups had statistically significant improvements in both endoscopic scoring (P \ .001) and SNOT-22 scores (P \ .001) (Table 2). When comparing outcomes between the prednisone and placebo groups, there were no significant differences in endoscopic grading or SNOT-22 outcomes at week 1, week 3, or month 2 (all P . .119) (Figures 2 and 3; Tables 3 and 4).
Discussion This randomized, double-blind, placebo-controlled trial has demonstrated that continuing a short course of postoperative systemic corticosteroids may not provide additional clinical benefit when utilizing a middle meatal steroid-eluting spacer after ESS. It is important to take these results into context of the perioperative medical therapy protocol, which included 7 days of preoperative systemic corticosteroids in
preparation for surgery. The findings suggest that the improved topical corticosteroid therapy delivery from the steroid-eluting spacer adequately controls postoperative mucosal inflammation and may preclude the use of continued postoperative systemic corticosteroid therapy. Reducing the duration of systemic corticosteroid therapy in CRS patients with nasal polyposis is important since it may reduce the potential short and long-term adverse effects associated with this therapy. Following a successful ESS procedure, an open and accessible sinus cavity will allow for continued medical therapy, which is critical for long-term success by minimizing mucosal inflammation. The use of topical sinonasal therapies immediately following ESS can be limited by nasal crusting, retained secretions, and mucosal edema. To overcome this challenge, many surgeons have advocated the use of postoperative systemic corticosteroids to improve surgical outcomes by reducing inflammation of the diseased mucosa in the early postoperative period following ESS. A randomized, double-blind, placebo-controlled study by Wright et al evaluated the effect of perioperative systemic corticosteroids (prednisone 30 mg PO QD for 5 days preoperatively followed by 9 days postoperatively) on surgical outcomes following ESS to determine whether the benefits of this treatment modality are justified given the potential for systemic adverse effects. While patient-reported outcomes did not significantly differ between groups, the patients receiving prednisone received significantly improved endoscopic scores at most time points
Downloaded from oto.sagepub.com at UNIV TORONTO on August 10, 2014
Dautremont et al
693
14 12 10 8 6 4 2 0 Preoperative
1 week postop Prednisone
3 weeks postop
2 months postop
Placebo
Figure 2. Endoscopic (Lund–Kennedy) grading comparison between prednisone and placebo groups when utilizing a middle meatal steroid eluting spacer.
70 60 50 40 30 20 10 0 Preoperative
1 week postop Prednisone
3 weeks postop
2 months postop
Placebo
Figure 3. Disease-specific quality of life (SNOT-22) score comparison between prednisone and placebo groups when utilizing a middle meatal steroid eluting spacer.
compared to the placebo group.8 Furthermore, there was improved visualization during ESS in the group of patients receiving preoperative prednisone. These results support the use of perioperative systemic corticosteroids in CRS patients with nasal polyposis. To further improve local drug delivery in the early postoperative period, drug eluting middle meatal spacers have been developed to provide a slow release of continuous topical therapy while removing the need for daily patient dependent delivery techniques and reducing the potential for noncompliance. A variety of off-label middle meatal spacers and corticosteroid variations have been described and evaluated. A randomized trial by Cote and Wright demonstrated a significant improvement in postoperative endoscopic grading when using a Nasopore spacer impregnated with 2 ml of triamcinolone (40 mg/ml) versus a spacer soaked in placebo.15 A study by More et al compared a triamcinolone
impregnated Nasopore spacer to a group treated with postoperative systemic corticosteroids alone and demonstrated no significant difference in the presence of nasal polyps postoperatively.13 A recent meta-analysis by Zhao et al evaluated steroid-eluting spacers and reported that they may reduce postoperative adhesion rates.22 FDA-approved bioabsorbable steroid-eluting stents have also been studied with favorable results. In a meta-analysis Han et al examined the effect of the Propelä mometasone-eluting sinus implant (Intersect ENT; Palo Alto, California) and found a significant decrease in recurrent sinonasal inflammation of a degree that would warrant the use of oral steroid, at postoperative day 30. The authors also found a reduction in postoperative polyp formation, turbinate lateralization and formation of adhesions that would warrant a surgical intervention.16 This meta-analysis received industry funding from the producer of the stent which was the subject of the study. The study by Cote and Wright used Nasopore dressings that were donated by Stryker Canada. However, this was an investigator-initiated study, and Stryker Canada had no involvement in study design, protocol, methods, or analysis. The authors of the remaining studies discussed above did not describe any industry sponsorship. Overall, the evidence suggests that the use of middle meatal steroid-eluting spacers following ESS provides topical corticosteroid effects and aids in controlling postoperative mucosal inflammation. Since systemic corticosteroids have the potential for both short-term risks and long-term cumulative dose effects, it would be important to identify management strategies to reduce the total duration of systemic corticosteroid use without compromising clinical outcomes.10,23 Although the use of preoperative systemic corticosteroids will likely continue, to optimize surgical conditions for patients with nasal polyposis, the use of middle meatal steroid-eluting spacers may represent a novel strategy to preclude the use of continued postoperative systemic corticosteroids. Results from this study suggest that the use of postoperative systemic corticosteroids failed to offer additional clinical benefit when using a middle meatal steroid-eluting spacer following ESS in CRS patients with nasal polyposis. Although all patients received preoperative systemic corticosteroids in preparation for ESS, a reduced treatment course by not continuing prednisone postoperatively may potentially reduce both shortterm and long-term adverse effects. There are certain limitations that should be considered when evaluating the findings from this study. First, a relatively small sample size may incur a risk of committing a type II error (accepting the null when it was false). While the sample size for this study was adequately powered to detect a difference in our primary outcome (ie, endoscopic score), a larger sample size would further reduce the risk of falsely accepting the null hypothesis. A second potential limitation is the relatively short length of follow-up for our final outcome (ie, 2 months). However, since the clinical impact for both the steroid-eluting spacer and postoperative systemic corticosteroid therapy should occur within the first 3 months after ESS, we do not feel a longer follow-up
Downloaded from oto.sagepub.com at UNIV TORONTO on August 10, 2014
694
Otolaryngology–Head and Neck Surgery 150(4)
Table 3. Endoscopic (Lund–Kennedy) Grading Comparison between Prednisone and Placebo Groups When Utilizing a Middle Meatal Steroid-eluting Spacer.
Week 1 Week 3 Month 2
Prednisone group (mean 6 SD)
Placebo group (mean 6 SD)
P value
6.5 6 1.4 5.1 6 2.3 2.2 6 1.6
6.3 6 1.2 5.0 6 2.2 1.7 6 1.5
.715 .883 .343
Table 4. Disease-specific Quality of Life (SNOT-22) Score Comparison between Prednisone and Placebo Groups When Utilizing a Middle Meatal Steroid-eluting Spacer.
Week 1 Week 3 Month 2
Prednisone group (mean 6 SD)
Placebo group (mean 6 SD)
P value
17.7 6 9.5 17.5 6 10.1 11.5 6 7.3
25.2 6 17.2 16.8 6 13.8 10.4 6 10.1
.119 .859 .722
Abbreviation: SNOT-22, Sinonasal Outcome Test.
period would change the outcomes of this study. Nonetheless, this study may have potentially missed a late effect of oral prednisone, beyond the 2-month period. While anecdotally this may seem unlikely, further study with a longer follow-up period may be needed to rule out this possibility. Third, patients in both groups received preoperative systemic corticosteroids (prednisone 30 mg PO QD 3 7 days), which will provide residual systemic effects into the postoperative period. However, the preoperative course was very short (7 days) and therefore would be unlikely to provide continued systemic effects up to the 2-month follow-up period.24 Furthermore, the aim of this study is to specifically evaluate the impact of postoperative systemic corticosteroid when using a middle meatal steroid-eluting spacer following ESS while employing a perioperative treatment strategy that reflects standard practice. Incorporating a research protocol that included preoperative systemic corticosteroids will provide generalizable outcomes to allow surgeons to apply these results to their current practice. Last, our study evaluated an off-label steroid-eluting spacer (Nasopore soaked with 2 ml of 40 mg/ml triamcinolone) and the results from this study may not be generalizable to other steroid-eluting spacers or stents, which may differ in their method of delivery and type of steroid. For example, the Propel sinus implant contains 370 mg mometasone furoate embedded in a polymer matrix that releases the drug over 30 days and does not require debridement following ESS.16 The off-label Nasopore triamcinolone method differs from the Propel method since it releases a very short burst of topical steroid over the first couple days until the remnant spacer is debrided in-office. The Nasopore-Triamcinolone method also differs in that triamcinolone is a potent topical steroid, with the local effect being observed even 2 months after placement of the absorbable spacer.15 Despite these limitations, we feel the randomized, double-blind, placebo-controlled study design strengthens the results and contributes to the literature by evaluating the
need for postoperative systemic corticosteroids in the era of drug-eluting spacers and stents.
Conclusion To reduce the risk of adverse effects, it is important to identify treatment strategies that minimize and reduce the duration of systemic corticosteroids in the management of CRS patients with nasal polyposis. Results from this study suggest that continuing a short course of postoperative systemic corticosteroids immediately following ESS for CRS with nasal polyposis may not provide additional clinical benefit when utilizing a middle meatal steroid-eluting spacer. Author Contributions Jon F. Dautremont, data analysis, manuscript writing, literature review, editing; Brad Mechor, patient enrollment, data collection, editing; Luke Rudmik, patient enrollment and evaluation, data collection and analysis, manuscript editing.
Disclosures Competing interests: None. Sponsorships: None. Funding source: None.
References 1. Kennedy D. Functional endoscopic sinus surgery technique. Arch Otolaryngol. 1985;111:643-649. 2. Soler ZM, Mace J, Smith TL. Symptom-based presentation of chronic rhinosinusitis and symptom-specific outcomes after endoscopic sinus surgery. Am J Rhinol. 2008;22:297-301. 3. Soler ZM, Smith TL. Quality of life outcomes after functional endoscopic sinus surgery. Otolaryngol Clin North Am. 2010; 43:605-612. 4. Smith TL, Batra PS, Seiden AM, Hannley M. Evidence supporting endoscopic sinus surgery in the management of adult
Downloaded from oto.sagepub.com at UNIV TORONTO on August 10, 2014
Dautremont et al
5.
6. 7.
8.
9.
10.
11.
12.
13.
14.
695
chronic rhinosinusitis: a systematic review. Am J Rhinol. 2005; 19:537-543. Smith TL, Litvack JR, Hwang PH, et al. Determinants of outcomes of sinus surgery: a multi-institutional prospective cohort study. Otolaryngol Head Neck Surg. 2012;142:55-63. Bhattacharyya N. Clinical outcomes after endoscopic sinus surgery. Curr Opin Allergy Clin Immunol. 2006;6:167-171. Rudmik L, Soler ZM, Orlandi RR, et al. Early post-operative care following endoscopic sinus surgery: an evidence-based review with recommendations. Int Forum Allergy Rhinol. 2011;1:417-430. Wright ED, Agrawal S. Impact of perioperative systemic steroids on surgical outcomes in patients with chronic rhinosinusitis with polyposis: evaluation with the novel perioperative sinus endoscopy (POSE) scoring system. Laryngoscope. 2007; 117:1-28. van Staa TP, Leufkens HG, Cooper C. The epidemiology of corticosteroid-induced osteoporosis: a meta-analysis. Osteoporos Int. 2002;13:777-787. Poetker DM, Reh DD. A comprehensive review of the adverse effects of systemic corticosteroids. Otolaryngol Clin North Am. 2010;43:753-768. Souverein PC, Berard A, Van Staa TP, et al. Use of oral glucocorticoids and risk of cardiovascular and cerebrovascular disease in a population based case-control study. Heart. 2004;90: 859-865. Murr AH, Smith TL, Hwang PH, et al. Safety and efficacy of a novel bioabsorbable, steroid-eluting sinus stent. Int Forum Allergy Rhinol. 2011;1:23-32. More Y, Willen S, Catalano P. Management of early nasal polyposis using a steroid-impregnated nasal dressing. Int Forum Allergy Rhinol. 2011;1:401-404. Rudmik L, Mace J, Mechor B. Effect of a dexamethasone Sinu-foamä middle meatal spacer on endoscopic sinus surgery
15.
16.
17.
18.
19.
20. 21.
22.
23.
24.
outcomes: a randomized, double-blind, placebo-controlled trial. Int Forum Allergy Rhinol. 2012;2:248-251. Cote DW, Wright ED. Triamcinolone-impregnated nasal dressing following endoscopic sinus surgery: a randomized, double-blind, placebo-controlled study. Laryngoscope. 2010; 120:1269-1273. Han JK, Marple BF, Smith TL, et al. Effect of steroidreleasing sinus implants on postoperative medical and surgical interventions: an efficacy meta-analysis. Int Forum Allergy Rhinol. 2012;2:271-279. Rosenfeld RM, Andes D, Bhattacharyya N, et al. Clinical practice guideline: adult sinusitis. Otolaryngol Head Neck Surg. 2007;31:S1-S31. Stanbury RM, Graham EM. Systemic corticosteroid therapy— side effects and their management. Br J Ophthalmol. 1998;82: 704-708. Rudmik LR, Mace J, Ferguson BJ, Smith TL. Concurrent septoplasty during endoscopic sinus surgery for chronic rhinosinusitis: does it confound outcomes assessment? Laryngoscope. 2011;121:2679-2683. Lund VJ, Kennedy DW. Staging for rhinosinustis. Ann Otol Rhinol Laryngol. 1995;104:17-21. Hopkins C, Gillett S, Slack R, Lund VJ, Browne JP. Psychometric validity of the 22-item Sinonasal Outcome Test. Clin Otolaryngol. 2009;34:447-454. Zhao X, Grewal A, Briel M, Lee JM. A systematic review of nonabsorbable, absorbable, and steroid-impregnated spacers following endoscopic sinus surgery. Int Forum Allergy Rhinol. 2013;3:896-904. Manson SC, Brown RE, Cerulli A, Vidaurre CF. The cumulative burden of oral corticosteroid side effects and the economic implications of steroid use. Respir Med. 2009;103:975-994. Frey BM, Frey FJ. Clinical pharmacokinetics of prednisone and prednisolone. Clin Pharmacokinet. 1990;19:126-146.
Downloaded from oto.sagepub.com at UNIV TORONTO on August 10, 2014
The Role of Immediate Postoperative Systemic Corticosteroids When Utilizing a Steroid-eluting Spacer Following Sinus Surgery Jon F. Dautremont, Brad Mechor and Luke Rudmik Otolaryngology -- Head and Neck Surgery 2014 150: 689 originally published online 30 January 2014 DOI: 10.1177/0194599814521373 The online version of this article can be found at: http://oto.sagepub.com/content/150/4/689
Published by: http://www.sagepublications.com
On behalf of:
American Academy of Otolaryngology- Head and Neck Surgery
Additional services and information for Otolaryngology -- Head and Neck Surgery can be found at: Email Alerts: http://oto.sagepub.com/cgi/alerts Subscriptions: http://oto.sagepub.com/subscriptions Reprints: http://www.sagepub.com/journalsReprints.nav Permissions: http://www.sagepub.com/journalsPermissions.nav
>> Version of Record - Apr 1, 2014 OnlineFirst Version of Record - Jan 30, 2014 What is This?
Downloaded from oto.sagepub.com at UNIV TORONTO on August 10, 2014
Original Research—Sinonasal Disorders
The Role of Immediate Postoperative Systemic Corticosteroids When Utilizing a Steroid-eluting Spacer Following Sinus Surgery
Otolaryngology– Head and Neck Surgery 2014, Vol. 150(4) 689–695 Ó American Academy of Otolaryngology—Head and Neck Surgery Foundation 2014 Reprints and permission: sagepub.com/journalsPermissions.nav DOI: 10.1177/0194599814521373 http://otojournal.org
Jon F. Dautremont, MD1, Brad Mechor, MD1, and Luke Rudmik, MD, MSc1
No sponsorships or competing interests have been disclosed for this article.
Keywords
Abstract
chronic rhinosinusitis, sinusitis, topical steroid, middle meatal spacer, sinus surgery, corticosteroid
Objective. Steroid-eluting spacers can improve local drug delivery immediately following endoscopic sinus surgery and reduce the recurrence of inflammation warranting systemic corticosteroids. For chronic rhinosinusitis with nasal polyposis, the need for systemic corticosteroids immediately following endoscopic sinus surgery when using a steroideluting spacer has not been studied. Study Design. A randomized, double-blind, placebo-controlled trial. Setting. Academic rhinology practice. Subjects and Methods. Chronic rhinosinusitis patients with nasal polyposis who failed medical therapy and elected endoscopic sinus surgery were enrolled. Patients were randomized into either the treatment arm (postoperative prednisone 30 mg daily 3 7 days; n = 18) or placebo arm (postoperative placebo pill daily 3 7 days; n = 18). Outcomes were evaluated at 1 week, 3 weeks, and 2 months postoperatively. Primary outcome was endoscopic grading at postoperative month 2 using the Lund–Kennedy system. Secondary outcome included disease-specific quality of life using the Sinonasal Outcome Test (SNOT-22) survey. Patient enrolment occurred from January 2012 through February 2013 (NCT01564355). Results. Both arms received significant improvement in endoscopic grading and disease-specific quality of life from baseline compared to 2-month follow-up (P \.001). There were no significant differences in mean endoscopic scores between the postoperative prednisone and control groups at 1 week (P = .715), 3 weeks (P = .883), or 2 months (P = .343). There were no significant differences in SNOT-22 scores between groups at all follow-up points (all P . .119). Conclusion. Minimizing systemic corticosteroid use in patients with chronic rhinosinusitis with nasal polyposis may avoid adverse events. Results from this study suggest that postoperative systemic corticosteroids immediately following endoscopic sinus surgery may not provide improved outcomes when utilizing a steroid-eluting spacer.
Received October 24, 2013; revised December 17, 2013; accepted January 7, 2014.
Introduction Endoscopic sinus surgery (ESS) is an excellent management option for patients with medically refractory chronic rhinosinusitis (CRS).1-6 An important goal in the early postoperative period is to minimize mucosal inflammation, promote normal ciliary function, and reduce the risk of complications such as synechiae and infection.7 To minimize postoperative mucosal inflammation, most experts would recommend high volume saline irrigations and early topical corticosteroid therapy.7 However, the early postoperative milieu of sinonasal crusting, retained secretions, and edema significantly impair adequate delivery of topical corticosteroid therapy immediately following ESS. To overcome this challenge, surgeons often consider providing a short course of postoperative systemic corticosteroids, which has been shown to significantly improve postoperative endoscopic outcomes in CRS patients with nasal polyposis.8 Although effective, the use of systemic corticosteroids has potential serious adverse effects and identifying strategies to reduce these risks while maintaining the clinical benefit would improve patient care.9-11 1
Division of Otolaryngology–Head and Neck Surgery, Department of Surgery, University of Calgary, Calgary, Alberta, Canada This article was presented at the 2013 AAO-HNSF Annual Meeting & OTO EXPO; September 29-October 3, 2013; Vancouver, British Columbia, Canada. Corresponding Author: Luke Rudmik, Division of Otolaryngology–Head and Neck Surgery, Department of Surgery, University of Calgary, Foothills Medical Centre, South Tower, Ste 602, 1403 29th St NW, T2N 2T9, Calgary, Alberta, Canada. Email: [email protected]
Downloaded from oto.sagepub.com at UNIV TORONTO on August 10, 2014
690
Otolaryngology–Head and Neck Surgery 150(4)
Drug eluting middle meatal spacers have been developed to deliver topical corticosteroid therapy without the need for spray, drop, or irrigation delivery techniques.12-15 In the early postoperative period following ESS, the use of drugeluting spacers has gained popularity since they can deliver topical corticosteroid to the sinonasal mucosa during a time when the traditional techniques of sprays and irrigations often fail due to impaired access from crusting and edema. Bioabsorbable steroid-eluting stents have also been shown to reduce the recurrence of sinonasal inflammation that would warrant systemic corticosteroid treatment, in the late postoperative period.16 Since drug-eluting spacers improve topical corticosteroid therapy in the immediate postoperative period, concurrent early postoperative systemic corticosteroid therapy may not be required. The purpose of this study is to evaluate the effectiveness of immediate postoperative systemic corticosteroid therapy when utilizing a middle meatal steroid-eluting spacer in CRS patients with nasal polyposis following ESS. The primary outcome was endoscopic grading and the secondary outcome was disease-specific quality of life (QoL). We hypothesized that continuing postoperative systemic corticosteroids would further improve endoscopic grading when utilizing a middle meatal steroid-eluting spacer following ESS for refractory CRS with nasal polyposis.
Methods and Materials Study Design This study is a randomized, double-blind, placebo-controlled trial (NCT01564355). Patients were enrolled between January 2012 and February 2013. Inclusion criteria included adults over 18 years of age, a diagnosis of CRS with nasal polyposis according to the 2007 Adult Sinusitis Guidelines,17 and elected ESS for an indication of refractory CRS. Refractory CRS was defined as persistent symptoms despite a minimum of 3 months topical corticosteroid spray or irrigations, minimum of a 2-week course of systemic corticosteroid (prednisone 30 mg PO once daily) and a minimum 2-week course of broad-spectrum antibiotic in the presence of mucopurulence. Exclusion criteria included patients with suspected systemic inflammatory disease, cystic fibrosis, and any contraindication to systemic corticosteroids.18 Patients undergoing concurrent septoplasty were not excluded as it has not been shown to be a confounding variable.19 Study protocol was approved by the University of Calgary Conjoint Health Research Ethics Board (Ethics ID: 24336), and informed consent was obtained from each study participant. Patients were randomized into either the intervention or placebo group (Figure 1). Patients in the intervention group received postoperative prednisone therapy (30 mg once daily 3 7 days) beginning 1 day after ESS. Patients in the control group received a postoperative placebo (once daily 3 7 days) beginning 1 day after ESS. Randomization was performed using a computer generated block-randomization allocation. The block size was 6. The enrolling surgeons (LR and BM) were blinded to the assigned group.
Preoperative Management In preparation for ESS, all enrolled patients received the same preoperative medications which included 7 days of oral prednisone (30 mg once daily) and 7 days of oral antibiotic. Antibiotic choice was either amoxicillin/clavulanate 875 mg twice daily, trimethoprim/sulfmethoxazole 160/800 mg twice daily (if penicillin allergy) or clarithromycin 500 mg twice daily (if penicillin and sulfa allergy).
Intraoperative Management All patients underwent ESS which included bilateral maxillary antrostomy, total ethmoidectomy, sphenoidotomy, and frontal sinusotomy. The surgeons were blinded to patient randomization. All patients had 1 Nasoporeä dissolvable spacer soaked with 2 ml of triamcinolone (40 mg/ml) placed into each of the ethmoid cavities at the completion of the ESS procedure.15 Nasopore is a co-polyetherester urethane foam that fragments within several days in the nasal cavity. Its high absorbency makes it useful as a carrier for fluid substances, as it can hold up to 25 times its weight in topical medication.
Postoperative Management Postoperative care followed appropriate evidence based recommendations and included the following protocol: high volume nasal saline irrigations (using a Neilmedä saline sinus rinse bottle) 3 times per day starting 1 day after ESS, continuing the systemic antibiotic for 7 days after ESS, and an endoscopic debridement at 1 and 3 weeks postoperatively.7 Topical nasal corticosteroid therapy was initiated at the 1 week postoperative visit. Topical steroid therapy following the debridement consisted of high volume budesonide irrigation once daily (1 mg in 240 ml of saline). This was initiated after the patient underwent their first nasal cavity debridement, which allowed for the effective delivery of topical steroid solution into the sinonasal cavity.
Data Collection Upon patient enrollment, baseline demographic information and preoperative Lund–Mackay computed tomography (CT) score were recorded. The primary outcome was endoscopic grading at postoperative month 2, which was collected using the validated 20-point Lund–Kennedy endoscopic scoring system, which assesses patients on the presence of polyps, edema, discharge, scarring, and crusting.20 The secondary outcome was disease-specific QoL at postoperative month 2, which was collected using the validated 22-item Sinonasal Outcome Test (SNOT-22) questionnaire.21 Data were collected in 2 tertiary rhinology clinics at 1 week, 3 weeks, and 2 months postoperatively. The surgeons were blinded to patient randomization throughout this period.
Statistical Analysis and Sample Size Calculation Completed survey data and scoring scales were collected, transcribed, and manually entered into a database by a trained study coordinator using standardized clinical research forms. Data were deidentified and securely stored during the data collection period (Microsoft Excel; Microsoft Corp, Redmond,
Downloaded from oto.sagepub.com at UNIV TORONTO on August 10, 2014
Dautremont et al
691 Assessed for eligibility (n=36)
Excluded (n=0)
Randomized (n=36)
Allocated to post-operative prednisone group (n=18) • Received prednisone (n=18) • Did not receive prednisone (n=18)
Allocated to post-operative placebo group (n=18) • Received placebo (n=18) • Did not receive placebo (n=18)
Pre-operative therapy (n=18) • Oral antibiotics x 7 days • Prednisone 30 mg daily x 7 days • Topical steroid rinse/spray
Pre-operative therapy (n=18) • Oral antibiotics x 7 days • Prednisone 30 mg daily x 7 days • Topical steroid rinse/spray
Surgery (n=18) • Minimum maxillary antrostomy, total ethmoidectomy • NasoporeTM spacer with 2 mL of 40 mg/mL triamcinolone
Surgery (n=18) • Minimum maxillary antrostomy, total ethmoidectomy • NasoporeTM spacer with 2 mL of 40 mg/mL triamcinolone
Post-operative therapy (n=18) • Oral antibiotics x 7 days • Prednisone 30 mg daily x 7 days • Nasal saline rinse starting POD #1 • Budesonide nasal rinse starting at week 1 • Debridement at 1 & 3 weeks
Post-operative therapy (n=18) • Oral antibiotics x 7 days • Placebo daily x 7 days • Nasal saline rinse starting POD #1 • Budesonide nasal rinse starting at week 1 • Debridement at 1 & 3 weeks
Lost to follow-up (n=0)
Lost to follow-up (n=0)
Analyzed (n=18) • Evaluation at 1-week, 3weeks, and 2-months postoperatively
Analyzed (n=18) • Evaluation at 1-week, 3weeks, and 2-months postoperatively
Figure 1. Randomized controlled trial study design and patient flow diagram.
Washington). All statistical analysis was performed using commercially available software (Stata 12.1; StataCorp LP, College Station, Texas). Descriptive statistics were provided for patient demographics including means and frequencies. For the primary and secondary outcomes, differences between the prednisone and placebo groups at 1 week, 3 weeks, and 2 months were analyzed using a 2-sided Student’s t test. Differences between groups from baseline to 2 months postoperatively were analyzed using a paired t test. P \ .05 was considered a statistically significant difference.
Based on the data published from the study by Wright et al we assumed a 25% improvement in mean Lund–Kennedy score.8 Using a 2-sample comparison of proportions with a power of 90% and an alpha of 5%, we calculated a sample size of 36 required, 18 in each treatment arm.
Results A total of 36 patients were enrolled. Eighteen patients were randomized into each group: (1) postoperative prednisone group and (2) postoperative placebo group. None of the
Downloaded from oto.sagepub.com at UNIV TORONTO on August 10, 2014
692
Otolaryngology–Head and Neck Surgery 150(4)
Table 1. Baseline Demographic and CRS Severity Comparisons between Prednisone and Placebo Groups. Characteristic
Prednisone group (n = 18)a
Placebo group (n = 18)a
P value
46.4 45 (8) 56 (10) 39 (7) 11 (2) 0 (0) 16.3 8.5 47.8
41.7 56 (10) 56 (10) 33 (6) 6 (1) 0 (0) 15.8 8.9 42.2
.411 .444 1.0 .120 .364 1.0 .696 .579 .355
Age, mean years Male gender, n Asthma, n Allergy, n ASA intolerance Smoker Lund–Mackay CT review (mean) Lund–Kennedy endoscopic appearance (mean) SNOT-22 (mean)
Abbreviations: ASA, acetylsalicyclic acid; CRS, chronic rhinosinusitis; CT, computed tomography; SNOT-22, Sinonasal Outcome Test. a Values are percentages with n values in parentheses, unless otherwise noted.
Table 2. Comparison of Baseline and Postoperative Outcomes When Utilizing a Middle Meatal Steroid-eluting Spacer.
Prednisone group Placebo group
Outcome
Baseline (mean 6 SD)
Month 2 postoperative (mean 6 SD)
Endoscopy grade SNOT-22 Endoscopy grade SNOT-22
8.5 6 2.1 47.8 6 18.2 8.9 6 2.6 42.2 6 18.1
2.2 6 1.6 11.5 6 7.3 1.7 6 1.5 10.4 6 10.1
Mean absolute difference 6 SD 6.2 36.4 7.2 31.8
6 2.3 6 20.3 6 3.1 6 18.7
P value \.001 \.001 \.001 \.001
Abbreviation: SNOT-22, Sinonasal Outcome Test.
patients were lost to follow-up. All patients in each group fully completed the assigned postoperative medical therapy and standardized postoperative care protocols. No patient discontinued therapy due to any reported adverse effect. As seen in Table 1, both patient groups were similar in terms of demographics and presence of CRS-related comorbid diseases (all P . .12). There were no significant differences between patient groups in any of the preoperative measures of disease severity, including Lund–Mackay CT scoring (P = .696), Lund–Kennedy endoscopic grading (P = .579), and SNOT-22 (P = .355). When comparing baseline scores to the final 2-month outcomes, both groups had statistically significant improvements in both endoscopic scoring (P \ .001) and SNOT-22 scores (P \ .001) (Table 2). When comparing outcomes between the prednisone and placebo groups, there were no significant differences in endoscopic grading or SNOT-22 outcomes at week 1, week 3, or month 2 (all P . .119) (Figures 2 and 3; Tables 3 and 4).
Discussion This randomized, double-blind, placebo-controlled trial has demonstrated that continuing a short course of postoperative systemic corticosteroids may not provide additional clinical benefit when utilizing a middle meatal steroid-eluting spacer after ESS. It is important to take these results into context of the perioperative medical therapy protocol, which included 7 days of preoperative systemic corticosteroids in
preparation for surgery. The findings suggest that the improved topical corticosteroid therapy delivery from the steroid-eluting spacer adequately controls postoperative mucosal inflammation and may preclude the use of continued postoperative systemic corticosteroid therapy. Reducing the duration of systemic corticosteroid therapy in CRS patients with nasal polyposis is important since it may reduce the potential short and long-term adverse effects associated with this therapy. Following a successful ESS procedure, an open and accessible sinus cavity will allow for continued medical therapy, which is critical for long-term success by minimizing mucosal inflammation. The use of topical sinonasal therapies immediately following ESS can be limited by nasal crusting, retained secretions, and mucosal edema. To overcome this challenge, many surgeons have advocated the use of postoperative systemic corticosteroids to improve surgical outcomes by reducing inflammation of the diseased mucosa in the early postoperative period following ESS. A randomized, double-blind, placebo-controlled study by Wright et al evaluated the effect of perioperative systemic corticosteroids (prednisone 30 mg PO QD for 5 days preoperatively followed by 9 days postoperatively) on surgical outcomes following ESS to determine whether the benefits of this treatment modality are justified given the potential for systemic adverse effects. While patient-reported outcomes did not significantly differ between groups, the patients receiving prednisone received significantly improved endoscopic scores at most time points
Downloaded from oto.sagepub.com at UNIV TORONTO on August 10, 2014
Dautremont et al
693
14 12 10 8 6 4 2 0 Preoperative
1 week postop Prednisone
3 weeks postop
2 months postop
Placebo
Figure 2. Endoscopic (Lund–Kennedy) grading comparison between prednisone and placebo groups when utilizing a middle meatal steroid eluting spacer.
70 60 50 40 30 20 10 0 Preoperative
1 week postop Prednisone
3 weeks postop
2 months postop
Placebo
Figure 3. Disease-specific quality of life (SNOT-22) score comparison between prednisone and placebo groups when utilizing a middle meatal steroid eluting spacer.
compared to the placebo group.8 Furthermore, there was improved visualization during ESS in the group of patients receiving preoperative prednisone. These results support the use of perioperative systemic corticosteroids in CRS patients with nasal polyposis. To further improve local drug delivery in the early postoperative period, drug eluting middle meatal spacers have been developed to provide a slow release of continuous topical therapy while removing the need for daily patient dependent delivery techniques and reducing the potential for noncompliance. A variety of off-label middle meatal spacers and corticosteroid variations have been described and evaluated. A randomized trial by Cote and Wright demonstrated a significant improvement in postoperative endoscopic grading when using a Nasopore spacer impregnated with 2 ml of triamcinolone (40 mg/ml) versus a spacer soaked in placebo.15 A study by More et al compared a triamcinolone
impregnated Nasopore spacer to a group treated with postoperative systemic corticosteroids alone and demonstrated no significant difference in the presence of nasal polyps postoperatively.13 A recent meta-analysis by Zhao et al evaluated steroid-eluting spacers and reported that they may reduce postoperative adhesion rates.22 FDA-approved bioabsorbable steroid-eluting stents have also been studied with favorable results. In a meta-analysis Han et al examined the effect of the Propelä mometasone-eluting sinus implant (Intersect ENT; Palo Alto, California) and found a significant decrease in recurrent sinonasal inflammation of a degree that would warrant the use of oral steroid, at postoperative day 30. The authors also found a reduction in postoperative polyp formation, turbinate lateralization and formation of adhesions that would warrant a surgical intervention.16 This meta-analysis received industry funding from the producer of the stent which was the subject of the study. The study by Cote and Wright used Nasopore dressings that were donated by Stryker Canada. However, this was an investigator-initiated study, and Stryker Canada had no involvement in study design, protocol, methods, or analysis. The authors of the remaining studies discussed above did not describe any industry sponsorship. Overall, the evidence suggests that the use of middle meatal steroid-eluting spacers following ESS provides topical corticosteroid effects and aids in controlling postoperative mucosal inflammation. Since systemic corticosteroids have the potential for both short-term risks and long-term cumulative dose effects, it would be important to identify management strategies to reduce the total duration of systemic corticosteroid use without compromising clinical outcomes.10,23 Although the use of preoperative systemic corticosteroids will likely continue, to optimize surgical conditions for patients with nasal polyposis, the use of middle meatal steroid-eluting spacers may represent a novel strategy to preclude the use of continued postoperative systemic corticosteroids. Results from this study suggest that the use of postoperative systemic corticosteroids failed to offer additional clinical benefit when using a middle meatal steroid-eluting spacer following ESS in CRS patients with nasal polyposis. Although all patients received preoperative systemic corticosteroids in preparation for ESS, a reduced treatment course by not continuing prednisone postoperatively may potentially reduce both shortterm and long-term adverse effects. There are certain limitations that should be considered when evaluating the findings from this study. First, a relatively small sample size may incur a risk of committing a type II error (accepting the null when it was false). While the sample size for this study was adequately powered to detect a difference in our primary outcome (ie, endoscopic score), a larger sample size would further reduce the risk of falsely accepting the null hypothesis. A second potential limitation is the relatively short length of follow-up for our final outcome (ie, 2 months). However, since the clinical impact for both the steroid-eluting spacer and postoperative systemic corticosteroid therapy should occur within the first 3 months after ESS, we do not feel a longer follow-up
Downloaded from oto.sagepub.com at UNIV TORONTO on August 10, 2014
694
Otolaryngology–Head and Neck Surgery 150(4)
Table 3. Endoscopic (Lund–Kennedy) Grading Comparison between Prednisone and Placebo Groups When Utilizing a Middle Meatal Steroid-eluting Spacer.
Week 1 Week 3 Month 2
Prednisone group (mean 6 SD)
Placebo group (mean 6 SD)
P value
6.5 6 1.4 5.1 6 2.3 2.2 6 1.6
6.3 6 1.2 5.0 6 2.2 1.7 6 1.5
.715 .883 .343
Table 4. Disease-specific Quality of Life (SNOT-22) Score Comparison between Prednisone and Placebo Groups When Utilizing a Middle Meatal Steroid-eluting Spacer.
Week 1 Week 3 Month 2
Prednisone group (mean 6 SD)
Placebo group (mean 6 SD)
P value
17.7 6 9.5 17.5 6 10.1 11.5 6 7.3
25.2 6 17.2 16.8 6 13.8 10.4 6 10.1
.119 .859 .722
Abbreviation: SNOT-22, Sinonasal Outcome Test.
period would change the outcomes of this study. Nonetheless, this study may have potentially missed a late effect of oral prednisone, beyond the 2-month period. While anecdotally this may seem unlikely, further study with a longer follow-up period may be needed to rule out this possibility. Third, patients in both groups received preoperative systemic corticosteroids (prednisone 30 mg PO QD 3 7 days), which will provide residual systemic effects into the postoperative period. However, the preoperative course was very short (7 days) and therefore would be unlikely to provide continued systemic effects up to the 2-month follow-up period.24 Furthermore, the aim of this study is to specifically evaluate the impact of postoperative systemic corticosteroid when using a middle meatal steroid-eluting spacer following ESS while employing a perioperative treatment strategy that reflects standard practice. Incorporating a research protocol that included preoperative systemic corticosteroids will provide generalizable outcomes to allow surgeons to apply these results to their current practice. Last, our study evaluated an off-label steroid-eluting spacer (Nasopore soaked with 2 ml of 40 mg/ml triamcinolone) and the results from this study may not be generalizable to other steroid-eluting spacers or stents, which may differ in their method of delivery and type of steroid. For example, the Propel sinus implant contains 370 mg mometasone furoate embedded in a polymer matrix that releases the drug over 30 days and does not require debridement following ESS.16 The off-label Nasopore triamcinolone method differs from the Propel method since it releases a very short burst of topical steroid over the first couple days until the remnant spacer is debrided in-office. The Nasopore-Triamcinolone method also differs in that triamcinolone is a potent topical steroid, with the local effect being observed even 2 months after placement of the absorbable spacer.15 Despite these limitations, we feel the randomized, double-blind, placebo-controlled study design strengthens the results and contributes to the literature by evaluating the
need for postoperative systemic corticosteroids in the era of drug-eluting spacers and stents.
Conclusion To reduce the risk of adverse effects, it is important to identify treatment strategies that minimize and reduce the duration of systemic corticosteroids in the management of CRS patients with nasal polyposis. Results from this study suggest that continuing a short course of postoperative systemic corticosteroids immediately following ESS for CRS with nasal polyposis may not provide additional clinical benefit when utilizing a middle meatal steroid-eluting spacer. Author Contributions Jon F. Dautremont, data analysis, manuscript writing, literature review, editing; Brad Mechor, patient enrollment, data collection, editing; Luke Rudmik, patient enrollment and evaluation, data collection and analysis, manuscript editing.
Disclosures Competing interests: None. Sponsorships: None. Funding source: None.
References 1. Kennedy D. Functional endoscopic sinus surgery technique. Arch Otolaryngol. 1985;111:643-649. 2. Soler ZM, Mace J, Smith TL. Symptom-based presentation of chronic rhinosinusitis and symptom-specific outcomes after endoscopic sinus surgery. Am J Rhinol. 2008;22:297-301. 3. Soler ZM, Smith TL. Quality of life outcomes after functional endoscopic sinus surgery. Otolaryngol Clin North Am. 2010; 43:605-612. 4. Smith TL, Batra PS, Seiden AM, Hannley M. Evidence supporting endoscopic sinus surgery in the management of adult
Downloaded from oto.sagepub.com at UNIV TORONTO on August 10, 2014
Dautremont et al
5.
6. 7.
8.
9.
10.
11.
12.
13.
14.
695
chronic rhinosinusitis: a systematic review. Am J Rhinol. 2005; 19:537-543. Smith TL, Litvack JR, Hwang PH, et al. Determinants of outcomes of sinus surgery: a multi-institutional prospective cohort study. Otolaryngol Head Neck Surg. 2012;142:55-63. Bhattacharyya N. Clinical outcomes after endoscopic sinus surgery. Curr Opin Allergy Clin Immunol. 2006;6:167-171. Rudmik L, Soler ZM, Orlandi RR, et al. Early post-operative care following endoscopic sinus surgery: an evidence-based review with recommendations. Int Forum Allergy Rhinol. 2011;1:417-430. Wright ED, Agrawal S. Impact of perioperative systemic steroids on surgical outcomes in patients with chronic rhinosinusitis with polyposis: evaluation with the novel perioperative sinus endoscopy (POSE) scoring system. Laryngoscope. 2007; 117:1-28. van Staa TP, Leufkens HG, Cooper C. The epidemiology of corticosteroid-induced osteoporosis: a meta-analysis. Osteoporos Int. 2002;13:777-787. Poetker DM, Reh DD. A comprehensive review of the adverse effects of systemic corticosteroids. Otolaryngol Clin North Am. 2010;43:753-768. Souverein PC, Berard A, Van Staa TP, et al. Use of oral glucocorticoids and risk of cardiovascular and cerebrovascular disease in a population based case-control study. Heart. 2004;90: 859-865. Murr AH, Smith TL, Hwang PH, et al. Safety and efficacy of a novel bioabsorbable, steroid-eluting sinus stent. Int Forum Allergy Rhinol. 2011;1:23-32. More Y, Willen S, Catalano P. Management of early nasal polyposis using a steroid-impregnated nasal dressing. Int Forum Allergy Rhinol. 2011;1:401-404. Rudmik L, Mace J, Mechor B. Effect of a dexamethasone Sinu-foamä middle meatal spacer on endoscopic sinus surgery
15.
16.
17.
18.
19.
20. 21.
22.
23.
24.
outcomes: a randomized, double-blind, placebo-controlled trial. Int Forum Allergy Rhinol. 2012;2:248-251. Cote DW, Wright ED. Triamcinolone-impregnated nasal dressing following endoscopic sinus surgery: a randomized, double-blind, placebo-controlled study. Laryngoscope. 2010; 120:1269-1273. Han JK, Marple BF, Smith TL, et al. Effect of steroidreleasing sinus implants on postoperative medical and surgical interventions: an efficacy meta-analysis. Int Forum Allergy Rhinol. 2012;2:271-279. Rosenfeld RM, Andes D, Bhattacharyya N, et al. Clinical practice guideline: adult sinusitis. Otolaryngol Head Neck Surg. 2007;31:S1-S31. Stanbury RM, Graham EM. Systemic corticosteroid therapy— side effects and their management. Br J Ophthalmol. 1998;82: 704-708. Rudmik LR, Mace J, Ferguson BJ, Smith TL. Concurrent septoplasty during endoscopic sinus surgery for chronic rhinosinusitis: does it confound outcomes assessment? Laryngoscope. 2011;121:2679-2683. Lund VJ, Kennedy DW. Staging for rhinosinustis. Ann Otol Rhinol Laryngol. 1995;104:17-21. Hopkins C, Gillett S, Slack R, Lund VJ, Browne JP. Psychometric validity of the 22-item Sinonasal Outcome Test. Clin Otolaryngol. 2009;34:447-454. Zhao X, Grewal A, Briel M, Lee JM. A systematic review of nonabsorbable, absorbable, and steroid-impregnated spacers following endoscopic sinus surgery. Int Forum Allergy Rhinol. 2013;3:896-904. Manson SC, Brown RE, Cerulli A, Vidaurre CF. The cumulative burden of oral corticosteroid side effects and the economic implications of steroid use. Respir Med. 2009;103:975-994. Frey BM, Frey FJ. Clinical pharmacokinetics of prednisone and prednisolone. Clin Pharmacokinet. 1990;19:126-146.
Downloaded from oto.sagepub.com at UNIV TORONTO on August 10, 2014
