Volume 45, Issue 02 January 21, 2012 STEROID THERAPY Intratympanic Steroid Therapy tion and morphology; reduce hearing loss in meningitis (ac- cording to Cochrane analysis); prevent loss of spiral ganglion David S. Haynes, MD, Clinical Associate Professor, Depart- neurons; modulate sodium/potassium in endolymph; regulate ment of Otolaryngology, Department of Hearing and Speech RNA transcriptional factors; ototoxicity (possibly outliers) Sciences, Vanderbilt Bill Wilkerson Center for Otolaryngol- Treatment with systemic steroids: Wilson et al (1980) — double- ogy and Communication Sciences, Vanderbilt University blind, placebo-controlled trial showed benefit with steroids; will Medical Center, Nashville, TN not be repeated due to ethics of entering patients into placebo arm; several papers show no benefit of steroids for sudden SNHL; Use of steroids: systemic therapy for sudden sensorineural hear- Conlin and Parnes (2007) — meta-analysis of 2 randomized, pla- ing loss (SNHL); intratympanic therapy for SNHL and ver- cebo-controlled trials examining benefits of steroids to treat sud- tigo; hearing preservation; surgery for cochlear implants den SNHL; found no benefit (systemic and intratympanic); possibly for all otologic surgery Intratympanic steroid therapy: same meaning — transtym- Idiopathic sudden SNHL: definition by Wilson et al (1980) — panic therapy; middle ear perfusion; inner ear perfusion; decline in hearing over 3 days affecting 3 frequencies by administration —intratympanic injection; MicroWick (off mar- 30 dB with no identifiable etiology; disproportionate interest ket); microcatheter; intraoperative irrigation; hydrogel; nanopar- in sudden SNHL (2,000 articles since 1966); reversible hear- ticles; methods—3 separate injections 10 min apart; never inject; ing loss; local expertise required; high degree of patient frus- 1 injection at completion tration; little evidence to suggest viral infection, bacterial Hydrogel: poly(D,L-lactic-co-glycolic acid) polymer; injected infection, vascular occlusion, or vasculitis as sole etiology as liquid; gels at body temperature and releases embedded Diagnosis: hearing test; magnetic resonance imaging (MRI); no medication in controlled mechanism; study — patients with blood tests unless fluctuating or bilateral hearing loss Meniere disease; high perilymph level maintained at high Proposed therapies: no double-blind, placebo-controlled trials (220 mg/mL) concentration support use; shotgun therapy — in the past, patients given all Methods of intracochlear delivery: coated electrode and os- available treatments at once due to multiple possible etiologies motic pumps; egress pathways connected to reservoir and limited time to treat; old (1994) regimen included steroids, Issues with injection: loss via eustachian tube; unknown whether carbogen inhalation, oral papaverine (Papacon, Para-Time absorbed systemically; highly absorbed in mucosa; unknown S.R., Pavabid Plateau), aspirin, and hydrochlorothiazide triam- whether vehicle should be highly viscous or less viscous; terene (Dyazide, Maxzide, Maxzide-25); no longer used would product with higher viscosity maintain round window Natural history: recovery rates for untreated patients, 31% to 65%; contact better; round window adhesions; concentration gradi- for treated patients, 35% to 89%; reasons for wide range — ent needed to maintain therapeutic effect; ototoxicity of preser- inconsistent definition of sudden SNHL; wide range of time vatives in vehicles; cochlear pharmacokinetics frames; inconsistent definitions of “success” and “failure” Debates: when to give; how to give; which steroid to use; how Standard initial treatment: methylprednisolone (Medrol, Medrol often; concentration; whether to give for sudden SNHL Dosepak, MethylPREDNISolone Dose Pack)—entire pack con- History: Itoh et al (1991) — first report on use of intratympanic tains 105 mg of drug; probably not enough; adequate dose un- steroids for inner ear disease; Silverstein et al (1996) — first re- known; methylprednisolone acetate (DepoMedrol) injection— port on intratympanic steroids for sudden SNHL highest available dose, 100 mg prednisone equivalent; common Timing: 3 choices — 1) at onset of systemic therapy; 2) as sal- dose—60 to 80 mg prednisone tapered over 10 days to 2 wk; larger vage if treatment with systemic therapy fails; 3) intratym- doses of methylprednisolone given for sudden visual loss panic steroids only (speaker does not recommend) Legal issues: inform patient of risks for avascular necrosis of hip, Dosing schedule: single day; weekly; multiple weeks with self- peptic ulcer, hyperglycemia, cataracts; standard of care— physi- administered drops; implantable pumps (taken off market) cian who does not give steroids may have violated standard of Literature review: low numbers of patients; different steroid types care, but physician also at risk if steroids given and complication and concentrations; most salvage; 0% to 100% improved; criteria occurs; legal term meaning that if action not taken physician has for reporting improvement modest; twice number of studies for violated standard of care and therefore committed malpractice sudden SNHL than Meniere disease; most did not have controls; Actions of steroids on cochlea: receptors in inner ear; decrease only 1 double-blind study; many did not use standard definition inflammation; improve blood flow; protect against ischemia Speaker’s data: excluded patients with Meniere disease or fluc- and noise-induced hearing loss; increase stria vascularis func- tuating hearing loss; 40 patients who failed despite treatment Educational Objectives Faculty Disclosure The goal of this program is to improve the management of patients In adherence to ACCME Standards for Commercial Support, Au- with sudden sensorineural hearing loss (SNHL) and patients with dio-Digest requires all faculty and members of the planning com- chronic rhinosinusitis (CRS) with polyps. After hearing and assimi- mittee to disclose relevant financial relationships within the past 12 lating this program, the clinician will be better able to: months that might create any personal conflicts of interest. Any 1. Discuss the reasons for the wide range of reported im- identified conflicts were resolved to ensure that this educational ac- provement of sudden SNHL with and without treatment. tivity promotes quality in health care and not a proprietary business 2. Review the actions of steroids on the cochlea. or commercial interest. For this program, the following has been 3. Treat sudden SNHL with systemic and intratympanic ste- disclosed: Dr. Haynes is a consultant for Advanced Bionics, Ans- roids. pach, Carl Zeiss, Cochlear Limited,and MED-EL. Dr. Murr is a consultant for and owns stock in Intersect ENT . The planning 4. Review the literature on topical (spray and irrigation) and committee reported nothing to discose. In their lectures, Drs. systemic steroids to treat nasal polyposis. Haynes and Murr present information that is related to the off-label 5. Treat patients with CRS and nasal polyposis using depos- or investigational use of a therapy, product, or device. ited steroid delivery methods. AUDIO-DIGEST OTOLARYNGOLOGY 45:02 for 1 wk with systemic therapy; intratympanic injection with (CRS) with polyps and had sufficient data to include in meta- 24 mg dexamethasone crystals in saline (mixed fresh every analysis; showed that intranasal steroids decrease polyp size; day); 40% showed any improvement; using criteria of 20 dB believed to result in improvement in nasal obstruction; study — improvement or 20% improvement in word understanding trend toward improvement in symptoms of cystic fibrosis (eg, scores, 27% improved; improvement in pure tone average, 16 nasal polyp obstruction) with topical steroid; Jankowski et al dB; average improvement in speech scores, 40%; 39% im- (2009) — fluticasone propionate aerosolized nasal spray, 200 µg proved if treated within 6 wk; 26% improved if treated be- twice daily (double Food and Drug Administration [FDA]-ap- tween 2 and 6 wk of symptom onset; few late recoveries; proved dose) compared to placebo at 1 mo, after 2 mo, and at 6 success range using criteria from previous articles, 12% to mo; within 2 mo of onset of nasal polyposis fluticasone at 200 60%; demonstrates need for standardization µg twice daily more effective than placebo alone, based on nasal Conclusions: dramatic late recoveries uncommon; literature rhinometry (ie, peak nasal expiratory flow) and patient-centered supports various definitions of success; clinical benefit of in- questionnaire; no significant difference between twice daily and tratympanic steroids difficult to prove; clinical use continues; once daily when measured to end point; conclusion — can use newer data suggest giving early probably better; emerging 200 µg once daily dose for long-term maintenance technologies for drug delivery Topical irrigation: budesonide inhalation (Pulmicort Respules); Questions and Answers not FDA approved; use through mucosal atomizer device or mixed into standard saline spray; Kanowitz et al (2008) — How would speaker treat self for sudden SNHL? systemic ste- roids; never proven that site of lesion in cochlea; possibly in good effect based on mucosal scale and patient questionnaire; cochlear nerve or intracranial; some pathology in vestibular decreased amount of oral steroids required to keep steroid-de- nerve (vestibular neuronitis) and facial nerve (Bell palsy); pendent patients comfortable; Sachanandani et al (2009) — would take single-dose, high concentration (24 mg/mL) intra- budesonide inhalation did not appear to cause suppression of tympanic steroids, probably early; by waiting for failure of adrenal-pituitary axis systemic steroids, may miss therapeutic window Systemic steroids: Cochrane database study — 3 randomized Initial testing for autoimmune disease: speaker does not use blood controlled studies; 166 patients; moderate to poor quality; tests; use trial of steroids to determine if patient has autoimmune suggested short-term benefit of oral steroids in patients with hearing loss; autoimmune testing does not change decision about multiple nasal polyps; parameters — endoscopic scale of whether to give steroids or how long to give them polyp size; symptom questionnaires; quality of life Oral steroids in addition to intratympanic steroid injection? Direct injection of steroids: Becker et al (2007)— 1500 injections yes in 358 patients who had medical treatment, medical treatment and Outcomes of study by Rauch showing no difference between injection, medical treatment and surgery, or medical treatment, in- oral and intratympanic steroids: showed probably no bene- jection, and surgery; 26 surgical complications; 1 complication fit to giving intratympanic steroids, despite most articles from injection (transient diplopia); used 0.5 to 1 mL in 50:50 mix- showing some benefit ture of triamcinolone acetonide suspension (Aristospan Injection, Stratification of data into mild, moderate, and profound Clinacort, Ken-Jec 40, Kenalog-10, Kenalog-40) with lidocaine SNHL: did not separate (not FDA approved); appeared to decrease frequency of surgery; no Elevated glucose levels in diabetic patients given intratym- evidence presented to directly relate to efficacy panic steroids alone? yes; dexamethasone highly absorbed in Deposited Steroid Delivery mucosa; during administration some enters eustachian tube; Carboxymethylcellulose (CMC): type of dressing foam; has plate- unknown if dexamethasone in saline passes through stomach let aggregation; normally mixed with 8 mL sterile water; possi- into intestines and absorbed ble to mix with 8 mL triamcinolone acetonide; 40 mg/mL Treating moderate hearing loss: same treatment for all patients triamcinolone (total dose, 160 mg per side); use as nasal dress- with sudden change in hearing, regardless of degree ing; advantages — excellent delivery localization; higher dose Standard time for patient to remain lying down after intra- than currently available commercially; no patient compliance tympanic steroid injection? no standard; speaker leaves pa- required; avoid side effects of systemic steroid tient a few minutes Pletcher and Goldberg (2010): 8 patients with CRS and persis- Need for more data: papers seem to support use of intratym- tent nasal polyposis despite functional endoscopic sinus sur- panic steroids, but still not clear gery (FESS); all patients failed aggressive postoperative steroid regimens; ceased saline irrigations for 48 hr; CMC New Methods for Steroid Delivery in Sinus Disease and triamcinolone improved scores on Sino-Nasal Outcome Andrew H. Murr, MD, Professor and Vice Chair, and Test-20 (SNOT 20) at 1 wk and 1 mo; correlated with scores Roger Boles, MD Endowed Chair In Otolaryngology Edu- on Perioperative Sinus Endoscopy (POSE) scale; scores on cation, Department of Otolaryngology–Head and Neck visual analog scale (VAS) better at 1 wk than 1 mo; Surgery, University of California, San Francisco, School limitations — subjective nature of endoscopic scoring scale; possible that CMC foam alone beneficial of Medicine; Chief of Otolaryngology–Head and Neck Potential benefits: may obviate need for oral steroid delivery in Surgery, San Francisco General Hospital postoperative period; greater convenience for patient; ability to Background: sinusitis — affects 16% of adults in United use in office States; 5 days work or school missed per year; costs $1500 Bioabsorbable steroid-eluting stent: background — FESS cen- per patient; annual medication costs, $1200 per patient; tered around reversibility of mucosal disease, preserving as 250,000 ethmoidectomies performed each year; sinusitis can much mucosa as possible; atraumatic surgical technique that occur with or without nasal polyps; can diagnose nasal polyps requires careful postoperative evaluation; causes of FESS in office with endoscope or computed tomography (CT) failure — recurrent inflammation and polyps; adhesions and Treatment of nasal polyps: antibiotics; antifungals; corticoste- synechiae; middle turbinate lateralization; stenosis of surgically roids; antileukotrienes; antihistamines; mast cell stabilizers; para- created ostia; to prevent complications — packing; stents; sympathetic blockade drugs; surgery; corticosteroid delivery — sponges; gels; medications to control inflammation topical (spray and irrigation); systemic; direct injection Stent: spring-like design; absorbable stent made from polylactide- Topical spray: Joe et al (2008) — of 1200 articles reviewed, 6 co-glycolide; infused with mometasone furoate (370 g); mo- pertained to use of topical steroids for chronic rhinosinusitis metasone 100 µg per day FDA-approved for allergic rhinitis; 200 AUDIO-DIGEST OTOLARYNGOLOGY 45:02 µg per day approved for polyps; placement— ethmoid cavity; Results: safety — no systemic steroid absorption; no suppression stent inserted with applicator device; mechanical function of adrenal-pituitary axis; statistically significant reduction in (opens middle meatus) and steroid delivery function inflammation at days 21, 28, and 45; middle turbinate position Study: prospective, multicenter, randomized, double-blind, not statistically significant; adhesion and polypoid change bet- controlled study; patients undergoing FESS for CRS with ter on steroid side; steroid dissolved by 1 mo and without nasal polyps; primary or revision surgery; stent Benefit of steroid elution: animal studies — adhesion rate without with steroid placed on one side and without steroid on other steroid, 21%; with steroid, 5%; historical comparison —21% side; intravenous steroids given perioperatively; no postop- to 25% adhesion rate with packing; benefits — avoid systemic erative steroids until day 30; course of antibiotics given; sa- side effects; more direct application of steroid; can decrease line spray permitted; minimum Lund-Mackay score, 6; all polyps and inflammation patients underwent bilateral ethmoidectomy Acknowledgements Dr. Haynes was recorded at Chicago Laryngological and Otological Society, held December 6, 2010, in Chicago, IL, and sponsored by Chicago Laryngological and Otological Society. Dr. Murr was recorded at UCSF Otolaryngology Update 2011, held November 10-12, 2011, in San Francisco, CA, and sponsored by the University of California, San Francisco, School of Medicine, Office of Continuing Medical Education. Information about upcoming events from the University of California, San Francisco, School of Medicine can be found at medschool2.ucsf.edu/medicaleducation. The Audio-Digest Foundation thanks the speakers and the sponsors for their cooper- ation in the production of this program. Suggested Reading uronic acid ester nasal dressing (Merogel) on intranasal wound heal- ing after functional endoscopic sinus surgery. Otolaryngol Head Neck Becker SS et al: Steroid injection for sinonasal polyps: the University Surg. 2003;128(6):862-9; Pletcher SD, Goldberg AN: Treatment of of Virginia experience. Am J Rhinol. 2007;21(1):64-9; Beer H et al: recurrent sinonasal polyposis with steroid-infused carboxymethylcel- Topical nasal steroids for treating nasal polyposis in people with cystic lulose foam. Am J Rhinol Allergy. 2010;24(6):451-3; Pondugula SR fibrosis. Cochrane Database Syst Rev. 2011(5):CD008253; Brouwer et al: Glucocorticoid regulation of genes in the amiloride-sensitive so- MC et al: Corticosteroids for acute bacterial meningitis. Cochrane dium transport pathway by semicircular canal duct epithelium of neo- Database Syst Rev. 2010(9):CD004405; Chen CY et al: Oral steroid natal rat. Physiol Genomics. 2006;24(2):114-23; Rauch SD et al: treatment of sudden sensorineural hearing loss: a ten year retrospec- Oral vs intratympanic corticosteroid therapy for idiopathic sud- tive analysis. Otol Neurotol. 2003;24(5):728-33; Conlin AE, Parnes den sensorineural hearing loss: a randomized trial. JAMA. LS: Treatment of sudden sensorineural hearing loss: II. A Meta-anal- 2011;305(20):2071-9; Sachanandani NS et al: The effect of nasally ysis. Arch Otolaryngol Head Neck Surg. 2007;133(6):582-6; De administered budesonide respules on adrenal cortex function in pa- Bosscher K et al: The interplay between the glucocorticoid receptor tients with chronic rhinosinusitis. Arch Otolaryngol Head Neck Surg. and nuclear factor-kappaB or activator protein-1: molecular mecha- 2009;135(3):303-7; Silverstein H et al: Intratympanic steroid treat- nisms for gene repression. Endocr Rev. 2003;24(4):488-522; Fuse T ment of inner ear disease and tinnitus (preliminary report). Ear Nose et al: Short-term outcome and prognosis of acute low-tone sensori- Throat J. 1996;75(8):468-71; Slattery WH et al: Oral steroid regi- neural hearing loss by administration of steroid. ORL J Otorhinolar- mens for idiopathic sudden sensorineural hearing loss. Otolaryngol yngol Relat Spec. 2002;64(1):6-10; Haynes DS et al: Intratympanic Head Neck Surg. 2005;132(1):5-10; Tabuchi K et al: Glucocorti- dexamethasone for sudden sensorineural hearing loss after failure of coids and dehydroepiandrosterone sulfate ameliorate ischemia-in- systemic therapy. Laryngoscope. 2007;117(1):3-15; Itoh A, Sakata duced injury of the cochlea. Hear Res. 2003;180(1-2):51-6; Wilson E: Treatment of vestibular disorders. Acta Otolaryngol Suppl. WR et al: The efficacy of steroids in the treatment of idiopathic sud- 1991;481:617-23; Jankowski R et al: Long-term study of fluticasone den hearing loss. A double-blind clinical study. Arch Otolaryngol. propionate aqueous nasal spray in acute and maintenance therapy of 1980;106(12):772-6; Wormald PJ et al: A prospective single-blind nasal polyposis. Allergy. 2009;64(6):944-50; Joe SA et al: A system- randomized controlled study of use of hyaluronic acid nasal packs in atic review of the use of intranasal steroids in the treatment of chronic patients after endoscopic sinus surgery. Am J Rhinol. 2006;20(1):7-10; rhinosinusitis. Otolaryngol Head Neck Surg. 2008;139(3):340-7; Worsoe L et al: Systemic steroid reduces long-term hearing Kanowitz SJ et al: Topical budesonide via mucosal atomization de- loss in experimental pneumococcal meningitis. Laryngoscope. vice in refractory postoperative chronic rhinosinusitis. Otolaryngol 2010;120(9):1872-9; Zadeh MH et al: Diagnosis and treatment of Head Neck Surg. 2008;139(1):131-6; Martinez-Devesa P, Patiar S: sudden-onset sensorineural hearing loss: a study of 51 patients. Oto- Oral steroids for nasal polyps. Cochrane Database Syst Rev. laryngol Head Neck Surg. 2003;128(1):92-8. 2011(7):CD005232; Miller RS et al: The clinical effects of hyal- Accreditation: The Audio-Digest Foundation is accredited by the Accred- each activity for 2.0 CE contact hours, including 0.5 pharmacology CE itation Council for Continuing Medical Education to provide continuing contact hours. medical education for physicians. The California State Board of Registered Nursing (CA BRN) accepts Designation: The Audio-Digest Foundation designates this enduring mate- courses provided for AMA PRA Category 1 Credit as meeting the continuing rial for a maximum of 2 AMA PRA Category 1 CreditsTM. Physicians should education requirements for license renewal. claim only the credit commensurate with the extent of their participation in Expiration: This CME activity qualifies for AMA PRA Category 1 Credit for the activity. 3 years from the date of publication. 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Listen to audio program 60 minutes Audio-Digest Foundation is approved as a provider of nurse practitioner Review written summary and suggested readings 35 minutes continuing education by the American Academy of Nurse Practitioners Take posttest 10 minutes (AANP Approved Provider number 030904). Audio-Digest designates AUDIO-DIGEST OTOLARYNGOLOGY 45:02 STEROID THERAPY To test online, go to www.audiodigest.org and sign in to online services. To submit a test form by mail or fax, complete Pretest section before listening and Posttest section after listening. 1. Which of the following diagnostic tests should be performed for a patient who presents with sudden unilateral, nonfluctuating sensorineural hearing loss (SNHL)? 1. Complete blood count 2. Audiography 3. Magnetic resonance imaging 4. Computed tomography (A) 1, 2 (B) 1, 2, 3 (C) 2, 3 (D) 2, 3, 4 2. Which of the following therapies for sudden SNHL continues to be used? (A) Carbogen inhalation (C) Hydrochlorothiazide triamterene (B) Oral papaverine (D) None of the above 3. The use of systemic steroids for treating sudden SNHL is almost universally supported in the literature. (A) True (B) False 4. Which of the following is known about intratympanic steroid therapy for sudden SNHL? (A) The steroid is absorbed in the mucosa (B) The steroid is absorbed systemically (C) Using a delivery vehicle with high viscosity is better at maintaining round window contact (D) It is most effective when given after systemic steroid therapy for 1 wk has failed 5. In a literature review of studies on intratympanic steroid therapy for sudden SNHL, the percentage of patients shown to improve ranged from: (A) 0% to 100% (B) 12% to 60% (C) 35% to 89% (D) 50% to 90% 6. Intratympanic steroid therapy is appropriate for patients with sudden SNHL that is: (A) Profound (B) Moderate or profound (C) Mild, moderate, or profound 7. Use of which of the following was shown in one study to decrease the amount of oral steroids required to keep steroid-dependent patients with chronic rhinosinusitis (CRS) comfortable? (A) Fluticasone propionate nasal spray (C) Beclomethasone dipropionate nasal spray (B) Budesonide inhalation (D) Triamcinolone acetonide as direct injection 8. In a study of 1500 direct steroid injections in 358 patients with CRS and polyps who had medical treatment, medical treatment and injection, medical treatment and surgery, or medical treatment, injection, and surgery, how many complications were associated with injections? (A) 1 (B) 12 (C) 26 (D) 35 9. Carboxymethylcellulose mixed with which drug is used for deposited steroid delivery for CRS with polyps? (A) Fluticasone propionate (C) Dexamethasone (B) Mometasone furoate (D) Triamcinolone acetonide 10. In a study of patients undergoing functional endoscopic sinus surgery for CRS, use of the bioabsorbable steroid- eluting stent resulted in all the following, except: (A) Reduction in inflammation (C) Polypoid change (B) Fewer adhesions compared to control (D) Prevention of middle turbinate lateralization Answers to Audio-Digest Otolaryngology Volume 45, Issue 01: 1-D, 2-B, 3-B, 4-A, 5-D, 6-C, 7-D, 8-C, 9-D, 10-D 2012 Audio-Digest Foundation • ISSN 0271-1354 • www.audiodigest.org Toll-Free Service Within the U.S. and Canada: 1-800-423-2308 • Service Outside the U.S. and Canada: 1-818-240-7500 Remarks represent viewpoints of the speakers, not necessarily those of the Audio-Digest Foundation.
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