Clinical Practice Guideline: Tonsillectomy in Children (Update).

OBJECTIVE: This update of a 2011 guideline developed by the American Academy of Otolaryngology-Head and Neck Surgery Foundation provides evidence-based recommendations on the pre-, intra-, and postoperative care and management of children 1 to 18 years of age under consideration for tonsillectomy. Tonsillectomy is defined as a surgical procedure performed with or without adenoidectomy that completely removes the tonsil, including its capsule, by dissecting the peritonsillar space between the tonsil capsule and the muscular wall. Tonsillectomy is one of the most common surgical procedures in the United States, with 289,000 ambulatory procedures performed annually in children <15 years of age based on the most recent published data. This guideline is intended for all clinicians in any setting who interact with children who may be candidates for tonsillectomy. PURPOSE: The purpose of this multidisciplinary guideline is to identify quality improvement opportunities in managing children under consideration for tonsillectomy and to create explicit and actionable recommendations to implement these opportunities in clinical practice. Specifically, the goals are to educate clinicians, patients, and/or caregivers regarding the indications for tonsillectomy and the natural history of recurrent throat infections. Additional goals include the following: optimizing the perioperative management of children undergoing tonsillectomy, emphasizing the need for evaluation and intervention in special populations, improving the counseling and education of families who are considering tonsillectomy for their children, highlighting the management options for patients with modifying factors, and reducing inappropriate or unnecessary variations in care. Children aged 1 to 18 years under consideration for tonsillectomy are the target patient for the guideline. For this guideline update, the American Academy of Otolaryngology-Head and Neck Surgery Foundation selected a panel representing the fields of nursing, anesthesiology, consumers, family medicine, infectious disease, otolaryngology-head and neck surgery, pediatrics, and sleep medicine. KEY ACTION STATEMENTS: The guideline update group made strong recommendations for the following key action statements (KASs): (1) Clinicians should recommend watchful waiting for recurrent throat infection if there have been <7 episodes in the past year, <5 episodes per year in the past 2 years, or <3 episodes per year in the past 3 years. (2) Clinicians should administer a single intraoperative dose of intravenous dexamethasone to children undergoing tonsillectomy. (3) Clinicians should recommend ibuprofen, acetaminophen, or both for pain control after tonsillectomy. The guideline update group made recommendations for the following KASs: (1) Clinicians should assess the child with recurrent throat infection who does not meet criteria in KAS 2 for modifying factors that may nonetheless favor tonsillectomy, which may include but are not limited to multiple antibiotic allergies/intolerance, PFAPA (periodic fever, aphthous stomatitis, pharyngitis, and adenitis), or history of >1 peritonsillar abscess. (2) Clinicians should ask caregivers of children with obstructive sleep-disordered breathing and tonsillar hypertrophy about comorbid conditions that may improve after tonsillectomy, including growth retardation, poor school performance, enuresis, asthma, and behavioral problems. (3) Before performing tonsillectomy, the clinician should refer children with obstructive sleep-disordered breathing for polysomnography if they are <2 years of age or if they exhibit any of the following: obesity, Down syndrome, craniofacial abnormalities, neuromuscular disorders, sickle cell disease, or mucopolysaccharidoses. (4) The clinician should advocate for polysomnography prior to tonsillectomy for obstructive sleep-disordered breathing in children without any of the comorbidities listed in KAS 5 for whom the need for tonsillectomy is uncertain or when there is discordance between the physical examination and the reported severity of oSDB. (5) Clinicians should recommend tonsillectomy for children with obstructive sleep apnea documented by overnight polysomnography. (6) Clinicians should counsel patients and caregivers and explain that obstructive sleep-disordered breathing may persist or recur after tonsillectomy and may require further management. (7) The clinician should counsel patients and caregivers regarding the importance of managing posttonsillectomy pain as part of the perioperative education process and should reinforce this counseling at the time of surgery with reminders about the need to anticipate, reassess, and adequately treat pain after surgery. (8) Clinicians should arrange for overnight, inpatient monitoring of children after tonsillectomy if they are <3 years old or have severe obstructive sleep apnea (apnea-hypopnea index ≥10 obstructive events/hour, oxygen saturation nadir <80%, or both). (9) Clinicians should follow up with patients and/or caregivers after tonsillectomy and document in the medical record the presence or absence of bleeding within 24 hours of surgery (primary bleeding) and bleeding occurring later than 24 hours after surgery (secondary bleeding). (10) Clinicians should determine their rate of primary and secondary posttonsillectomy bleeding at least annually. The guideline update group made a strong recommendation against 2 actions: (1) Clinicians should not administer or prescribe perioperative antibiotics to children undergoing tonsillectomy. (2) Clinicians must not administer or prescribe codeine, or any medication containing codeine, after tonsillectomy in children younger than 12 years. The policy level for the recommendation about documenting recurrent throat infection was an option: (1) Clinicians may recommend tonsillectomy for recurrent throat infection with a frequency of at least 7 episodes in the past year, at least 5 episodes per year for 2 years, or at least 3 episodes per year for 3 years with documentation in the medical record for each episode of sore throat and ≥1 of the following: temperature >38.3°C (101°F), cervical adenopathy, tonsillar exudate, or positive test for group A beta-hemolytic streptococcus. DIFFERENCES FROM PRIOR GUIDELINE: (1) Incorporating new evidence profiles to include the role of patient preferences, confidence in the evidence, differences of opinion, quality improvement opportunities, and any exclusion to which the action statement does not apply. (2) There were 1 new clinical practice guideline, 26 new systematic reviews, and 13 new randomized controlled trials included in the current guideline update. (3) Inclusion of 2 consumer advocates on the guideline update group. (4) Changes to 5 KASs from the original guideline: KAS 1 (Watchful waiting for recurrent throat infection), KAS 3 (Tonsillectomy for recurrent infection with modifying factors), KAS 4 (Tonsillectomy for obstructive sleep-disordered breathing), KAS 9 (Perioperative pain counseling), and KAS 10 (Perioperative antibiotics). (5) Seven new KASs: KAS 5 (Indications for polysomnography), KAS 6 (Additional recommendations for polysomnography), KAS 7 (Tonsillectomy for obstructive sleep apnea), KAS 12 (Inpatient monitoring for children after tonsillectomy), KAS 13 (Postoperative ibuprofen and acetaminophen), KAS 14 (Postoperative codeine), and KAS 15a (Outcome assessment for bleeding). (6) Addition of an algorithm outlining KASs. (7) Enhanced emphasis on patient and/or caregiver education and shared decision making.

Clinical Practice Guideline: Tonsillectomy in Children (Update)-Executive Summary.

OBJECTIVE: This update of a 2011 guideline developed by the American Academy of Otolaryngology-Head and Neck Surgery Foundation provides evidence-based recommendations on the pre-, intra-, and postoperative care and management of children 1 to 18 years of age under consideration for tonsillectomy. Tonsillectomy is defined as a surgical procedure performed with or without adenoidectomy that completely removes the tonsil, including its capsule, by dissecting the peritonsillar space between the tonsil capsule and the muscular wall. Tonsillectomy is one of the most common surgical procedures in the United States, with 289,000 ambulatory procedures performed annually in children <15 years of age, based on the most recent published data. This guideline is intended for all clinicians in any setting who interact with children who may be candidates for tonsillectomy. PURPOSE: The purpose of this multidisciplinary guideline is to identify quality improvement opportunities in managing children under consideration for tonsillectomy and to create explicit and actionable recommendations to implement these opportunities in clinical practice. Specifically, the goals are to educate clinicians, patients, and/or caregivers regarding the indications for tonsillectomy and the natural history of recurrent throat infections. Additional goals include the following: optimizing the perioperative management of children undergoing tonsillectomy, emphasizing the need for evaluation and intervention in special populations, improving the counseling and education of families who are considering tonsillectomy for their children, highlighting the management options for patients with modifying factors, and reducing inappropriate or unnecessary variations in care. Children aged 1 to 18 years under consideration for tonsillectomy are the target patient for the guideline. For this guideline update, the American Academy of Otolaryngology-Head and Neck Surgery Foundation selected a panel representing the fields of nursing, anesthesiology, consumers, family medicine, infectious disease, otolaryngology-head and neck surgery, pediatrics, and sleep medicine. KEY ACTION STATEMENTS: The guideline update group made strong recommendations for the following key action statements (KASs): (1) Clinicians should recommend watchful waiting for recurrent throat infection if there have been <7 episodes in the past year, <5 episodes per year in the past 2 years, or <3 episodes per year in the past 3 years. (2) Clinicians should administer a single intraoperative dose of intravenous dexamethasone to children undergoing tonsillectomy. (3) Clinicians should recommend ibuprofen, acetaminophen, or both for pain control after tonsillectomy. The guideline update group made recommendations for the following KASs: (1) Clinicians should assess the child with recurrent throat infection who does not meet criteria in KAS 2 for modifying factors that may nonetheless favor tonsillectomy, which may include but are not limited to multiple antibiotic allergies/intolerance, PFAPA (periodic fever, aphthous stomatitis, pharyngitis, and adenitis), or history of >1 peritonsillar abscess. (2) Clinicians should ask caregivers of children with obstructive sleep-disordered breathing and tonsillar hypertrophy about comorbid conditions that may improve after tonsillectomy, including growth retardation, poor school performance, enuresis, asthma, and behavioral problems. (3) Before performing tonsillectomy, the clinician should refer children with obstructive sleep-disordered breathing for polysomnography if they are <2 years of age or if they exhibit any of the following: obesity, Down syndrome, craniofacial abnormalities, neuromuscular disorders, sickle cell disease, or mucopolysaccharidoses. (4) The clinician should advocate for polysomnography prior to tonsillectomy for obstructive sleep-disordered breathing in children without any of the comorbidities listed in KAS 5 for whom the need for tonsillectomy is uncertain or when there is discordance between the physical examination and the reported severity of obstructive sleep-disordered breathing. (5) Clinicians should recommend tonsillectomy for children with obstructive sleep apnea documented by overnight polysomnography. (6) Clinicians should counsel patients and caregivers and explain that obstructive sleep-disordered breathing may persist or recur after tonsillectomy and may require further management. (7) The clinician should counsel patients and caregivers regarding the importance of managing posttonsillectomy pain as part of the perioperative education process and should reinforce this counseling at the time of surgery with reminders about the need to anticipate, reassess, and adequately treat pain after surgery. (8) Clinicians should arrange for overnight, inpatient monitoring of children after tonsillectomy if they are <3 years old or have severe obstructive sleep apnea (apnea-hypopnea index ≥10 obstructive events/hour, oxygen saturation nadir <80%, or both). (9) Clinicians should follow up with patients and/or caregivers after tonsillectomy and document in the medical record the presence or absence of bleeding within 24 hours of surgery (primary bleeding) and bleeding occurring later than 24 hours after surgery (secondary bleeding). (10) Clinicians should determine their rate of primary and secondary posttonsillectomy bleeding at least annually. The guideline update group made a strong recommendation against 2 actions: (1) Clinicians should not administer or prescribe perioperative antibiotics to children undergoing tonsillectomy. (2) Clinicians must not administer or prescribe codeine, or any medication containing codeine, after tonsillectomy in children younger than 12 years. The policy level for the recommendation about documenting recurrent throat infection was an option: (1) Clinicians may recommend tonsillectomy for recurrent throat infection with a frequency of at least 7 episodes in the past year, at least 5 episodes per year for 2 years, or at least 3 episodes per year for 3 years with documentation in the medical record for each episode of sore throat and ≥1 of the following: temperature >38.3°C (101°F), cervical adenopathy, tonsillar exudate, or positive test for group A beta-hemolytic streptococcus. DIFFERENCES FROM PRIOR GUIDELINE: Incorporating new evidence profiles to include the role of patient preferences, confidence in the evidence, differences of opinion, quality improvement opportunities, and any exclusion to which the action statement does not apply. There were 1 new clinical practice guideline, 26 new systematic reviews, and 13 new randomized controlled trials included in the current guideline update. Inclusion of 2 consumer advocates on the guideline update group. Changes to 5 KASs from the original guideline: KAS 1 (Watchful waiting for recurrent throat infection), KAS 3 (Tonsillectomy for recurrent infection with modifying factors), KAS 4 (Tonsillectomy for obstructive sleep-disordered breathing), KAS 9 (Perioperative pain counseling), and KAS 10 (Perioperative antibiotics). Seven new KASs: KAS 5 (Indications for polysomnography), KAS 6 (Additional recommendations for polysomnography), KAS 7 (Tonsillectomy for obstructive sleep apnea), KAS 12 (Inpatient monitoring for children after tonsillectomy), KAS 13 (Postoperative ibuprofen and acetaminophen), KAS 14 (Postoperative codeine), and KAS 15a (Outcome assessment for bleeding). Addition of an algorithm outlining KASs. Enhanced emphasis on patient and/or caregiver education and shared decision making.

Comparison of intranasal administration of haloperidol with intravenous and intramuscular administration: a pilot pharmacokinetic study.

STUDY OBJECTIVE: To evaluate the pharmacokinetics of haloperidol after intranasal administration compared with intravenous and intramuscular administration, and to evaluate systemic and local tolerance of intranasal administration. DESIGN: Randomized, open-label, three-way crossover study. SETTING: Academic medical center. SUBJECTS: Four healthy volunteers (two men, two women; aged 24-37 yrs). INTERVENTION: Each subject received in a randomized order the following three treatments, with a 2-week washout period between treatments: intravenous haloperidol 2.5 mg (0.5 ml of 5.0 mg/ml) infused over 15 minutes, intramuscular haloperidol 2.5 mg (0.5 ml of 5.0 mg/ml), and intranasal haloperidol 2.5 mg (2.5 mg/0.1-ml spray into a single naris). MEASUREMENTS AND MAIN RESULTS: Blood samples were obtained serially and plasma levels determined. Noncompartmental analysis was used to estimate pharmacokinetic parameters. Physical and nasal examinations and adverse-effect profiles were obtained to assess tolerance. Mean (percent coefficient of variation) haloperidol bioavailability after intranasal administration was 63.8% (24.4%) compared with intravenous administration and 48.6% (29.4%) compared with intramuscular administration. Intranasal administration achieved higher peak levels that occurred more quickly compared with intramuscular administration. Median time to maximum concentration was 15 minutes after the intranasal dose compared with 37.5 and 15 minutes after the intramuscular and intravenous doses, respectively. Subjects had mild-to-moderate systemic adverse effects, all related to an extension of haloperidol's pharmacologic actions. Two of the four subjects complained of mild-tomoderate nasal irritation after the intranasal doses. CONCLUSION: Our results suggest that additional research studies are warranted for further evaluation of intranasal administration of haloperidol. The product provides rapid therapeutic plasma levels and sedation, with only minor and short-lived nasal irritation. These data suggest that intranasal administration of haloperidol, or other antipsychotics with similar potency, could play a role in treating psychiatric emergencies.

Management of frontal sinus fractures: a review of 96 cases.

OBJECTIVES: The optimal treatment algorithm for frontal sinus fracture management remains ill-defined. The purpose of the study was to classify fracture types, review management methods, document associated injuries, and identify complications associated with various treatment options. STUDY DESIGN: The authors conducted a retrospective chart review evaluating a 13-year experience with frontal sinus fracture management. METHODS: Complete medical records of 96 frontal sinus fracture patients treated by the University of Kentucky Otolaryngology Service from 1990 to 2003 were reviewed. RESULTS: The average patient age was 39 years. Fifty percent of the fractures involved the anterior table of the frontal sinus alone, and 50% involved both anterior and posterior tables. Forty-seven percent of the injuries were managed with observation, whereas 50% of patients underwent surgical repair. In the surgical group, 60% underwent open reduction and internal fixation (ORIF), 23% had a cranialization procedure, and 17% underwent sinus obliteration. The average length of follow up was 9 months. Complications occurred in 17% of the patients (5% in the nonsurgical group and 12% in the surgical group). CONCLUSION: Our results support conservative management of nondisplaced or minimally displaced fractures based on the low complication rate seen in this series. Significant bone displacement can frequently be managed with simple ORIF. Complex fractures affecting the orbit or intracranial contents require cranialization or possibly obliteration. A subset of patients with suspected frontal sinus outflow obstruction can be considered for observation or simple ORIF with close follow up and endoscopic repair if outflow complications manifest.

Pharmacokinetics and pharmacodynamics of a new intranasal midazolam formulation in healthy volunteers.

We evaluated the pharmacokinetics and pharmacodynamics of single 5-mg doses of midazolam after administration of a novel intranasal (IN) formula, IM, and IV midazolam in an open-label, randomized, 3-way cross-over study in 12 healthy volunteers. IN doses were delivered as 0.1-mL unit-dose sprays of a novel formulation into both naris. Blood samples were taken serially from 0 to 12 h after each dose. Plasma midazolam concentrations were determined by liquid chromatography/mass spectrometry/mass spectrometry. Noncompartmental analysis was used to estimate pharmacokinetic parameters. The mean midazolam bioavailabilities and % coefficient of variation were 72.5 (12) and 93.4 (12) after the IN and IM doses, respectively. Median time to maximum concentration was 10 min for IN doses. Adverse events were minimal with all routes of administration, but nasopharyngeal irritation, eyes watering, and a bad taste were reported after IN doses. Our results support further development of this novel midazolam nasal spray.

Bioavailability of intranasal butorphanol administered from a single-dose sprayer.

PURPOSE: The bioavailability and tolerability of single doses of intranasal butorphanol tartrate using a single-dose, metered sprayer were studied. METHODS: In this open-label, randomized, three-way crossover study, 24 healthy volunteers received three treatments: (1) 2 mg of i.v. butorphanol (treatment A), (2) 2 mg of intranasal butorphanol (treatment B), and (3) 1 mg of intranasal butorphanol (treatment C). The three treatments received by each subject were separated by six-day washout periods. Venous blood samples (10 mL each) were obtained from an indwelling catheter at 0 (predose), 5, 10, 15,20,30, and 45 minutes and 1,2,3,4,6,8, 12, and 16 hours after butorphanol administration. Pharmacokinetic parameters were determined using standard noncompartmental methods with log-linear least-squares regression analysis to determine the elimination-rate constants. RESULTS: Intranasal butorphanol 1 and 2 mg administered using unit dose sprayers had a mean bioavailability of approximately 80%, which is higher than the percentage reported with the commercially available multidose product (61-69%). The absorption of intranasal butorphanol was rapid, with a median time to reach maximum concentration of 20 minutes (range, 10-60 minutes). Elimination profiles were comparable among all treatments. There were no clinically significant changes in the results of physical examinations, nasal evaluations, or laboratory tests related to butorphanol treatment. Most adverse effects reported were mild to moderate and as expected for this drug. CONCLUSION: Single-dose intranasal butorphanol was rapidly absorbed and had high absolute bioavailability in healthy volunteers.

Clinical Consensus Statement: Septoplasty with or without Inferior Turbinate Reduction.

OBJECTIVE: To develop a clinical consensus statement on septoplasty with or without inferior turbinate reduction. METHODS: An expert panel of otolaryngologists with no relevant conflicts of interest was assembled to represent general otolaryngology and relevant subspecialty societies. A working definition of septoplasty with or without inferior turbinate reduction and the scope of pertinent otolaryngologic practice were first established. Patients 18 years and older were defined as the targeted population of interest. A modified Delphi method was then used to distill expert opinion into clinical statements that met a standardized definition of consensus. RESULTS: The group defined nasal septoplasty as a surgical procedure designed to correct a deviated nasal septum for the purpose of improving nasal function, form, or both. After 2 iterative Delphi method surveys, 20 statements met the standardized definition of consensus, while 13 statements did not. The clinical statements were grouped into 8 categories for presentation and discussion: (1) definition and diagnosis, (2) imaging studies, (3) medical management prior to septoplasty, (4) perioperative management, (5) surgical considerations, (6) adjuvant procedures, (7) postoperative care, and (8) outcomes. CONCLUSION: This clinical consensus statement was developed by and for otolaryngologists and is intended to promote appropriate and, when possible, evidence-based care for patients undergoing septoplasty with or without inferior turbinate reduction. A complete definition of septoplasty with or without inferior turbinate reduction was first developed, and additional statements were subsequently produced and evaluated addressing diagnosis, medical management prior to septoplasty, and surgical considerations, as well as the appropriate role of perioperative, postoperative, and adjuvant procedures, in addition to outcomes. Additionally, a series of clinical statements were developed, such as "Computed tomography scan may not accurately demonstrate the degree of septal deviation," "Septoplasty can assist delivery of intranasal medications to the nasal cavity," "Endoscopy can be used to improve visualization of posterior-based septal deviation during septoplasty," and "Quilting sutures can obviate the need for nasal packing after septoplasty." It is anticipated that the application of these principles will result in decreased variations in the care of septoplasty patients and an increase in the quality of care.

Effect of fluticasone propionate nasal spray on bioavailability of intranasal hydromorphone hydrochloride in patients with allergic rhinitis.

STUDY OBJECTIVE: To investigate the effect of the nasal corticosteroid fluticasone propionate on the bioavailability and pharmacokinetics of single-dose intranasal hydromorphone hydrochloride in patients with allergic rhinitis. DESIGN: Randomized, three-way, crossover pharmacokinetic study. SETTING: University clinical research unit. PATIENTS: Twelve patients with allergic rhinitis. INTERVENTION: Hydromorphone hydrochloride 2.0 mg was administered by intravenous infusion (treatment A), intranasal spray without allergic rhinitis treatment (treatment B), and intranasal spray after 6 days of fluticasone propionate (treatment C). Blood samples were collected serially from 0-16 hours. MEASUREMENTS AND MAIN RESULTS: Pharmacokinetic parameters were determined by noncompartmental methods. An analysis of variance (ANOVA) model was used for statistical analysis. Mean (% coefficient of variation) absolute bioavailability of intranasal hydromorphone was 51.9% (28.2) and 46.9% (30.3) in patients with allergic rhinitis with and without treatment with fluticasone propionate, respectively. Mean maximum concentration (Cmax) values were 3.02 and 3.56 ng/ml, respectively. No statistical differences in Cmax and area under the concentration versus time curve were detected between intranasal treatments. Bioavailability values for both intranasal treatments were lower than those in healthy volunteers (57%). Median time to Cmax (Tmax) values were significantly different (p=0.02) for treatments B and C (15 and 30 min, respectively) using rank-transformed Tmax for ANOVA. Adverse effects were consistent with known effects of hydromorphone administered by other routes, with the exception of bad taste after intranasal administration. CONCLUSION: Hydromorphone was rapidly absorbed after nasal administration, with maximum concentrations occurring for most subjects within 30 minutes. Allergic rhinitis may affect pain management strategies for intranasal hydromorphone, with a delay in onset of action for patients treated with fluticasone propionate.

Pharmacokinetics of butorphanol tartrate administered from single-dose intranasal sprayer.

PURPOSE: The pharmacokinetics and tolerability of single and multiple doses of intranasal butorphanol tartrate using a single-dose metered sprayer were studied. METHODS: In this randomized, open-label, two-way crossover study, 24 healthy subjects received either 1 or 2 mg of intranasal butorphanol as a single dose (treatment A) and 1 or 2 mg of intranasal butorphanol every six hours for seven doses (treatment B). During phase 1, 12 subjects selected at random received a single 1-mg dose and the other 12 a single 2-mg dose. During phase 2, those who received the 1-mg single dose received 1 mg every six hours for seven doses. During phase 3, those who received the 2-mg single dose received 2 mg every six hours for seven doses. Serial blood samples were collected over 12 hours. Pharmacokinetic parameters were determined using noncompartmental methods. RESULTS: Mean (coefficient of variation) values for the area under the concentration-versus-time curve (AUC) from time zero to infinity (AUC0-infinity) were 4.15 (26.4%) and 10.42 (19.6%) ng.hr/ml after single doses of 1 and 2 mg of butorphanol, respectively. At steadly state, mean values for the AUC from time zero to the dosing interval (AUC0-tau) were 4.82 (40.2%) and 10.60 (22.3%) ng.hr/mL, respectively. The accumulation indices were around 2 for both the 1- and 2-mg doses. Median time to maximum concentration values ranged from 15 to 30 minutes for each treatment. Dose-normalized parameters AUC0-infinity. AUC0-tau and maximum concentration (Cmax) were significantly larger after a single 2-mg versus 1-mg dose (p < 0.05). CONCLUSION: Intranasal butorphanol has rapid absorption and predictable accumulation after multiple doses administered with single-dose metered sprayers. Intranasal administration of butorphanol was well tolerated and adverse events were generally mild to moderate in severity and as expected for this drug.

Bioavailability and pharmacokinetics of intranasal hydromorphone in patients experiencing vasomotor rhinitis.

BACKGROUND AND OBJECTIVE: Narcotic analgesics such as hydromorphone undergo an extensive first-pass effect resulting in a low systemic bioavailability following oral administration. Alternative dosing routes, such as rectal and intranasal (IN) routes, have been suggested as options for oral or intravenous administration. Rhinitis and pharmacological agents used for treatment are considered factors that could alter the rate and extent of absorption of drugs administered by the nasal route. The purpose of this study was to evaluate the pharmacokinetics of intranasal hydromorphone hydrochloride (HCl) in patients with vasomotor rhinitis. METHODS: Ten patients completed the randomised, three-way crossover study. During the three treatment periods, a single dose of hydromorphone HCl 2.0mg was administered via intravenous infusion (treatment A) and the intranasal route without (treatment B) or with (treatment C) vasoconstrictor pretreatment for rhinitis. Blood samples were collected serially from 0 to 16 hours. Noncompartmental methods were used to determine pharmacokinetic parameters. RESULTS: Maximum plasma concentrations were 3.69 and 3.38 mug/L for treatments B and C, respectively. Mean (% coefficient of variation) bioavailability of intranasal hydromorphone was 54.4% (34.8) and 59.8% (22.1) with and without pretreatment, respectively. Pretreatment of rhinitis did not significantly affect the rate or extent of absorption of hydromorphone in this study. There was not a significant difference in bioavailability between treated and untreated rhinitis. CONCLUSIONS: This study found intranasal administration of hydromorphone in patients experiencing vasomotor rhinitis had acceptable bioavailability and a pharmacokinetic profile comparable to previous studies. These data support further investigation of this single-dose delivery system for clinical use.

Clinical practice guideline: tinnitus.

OBJECTIVE: Tinnitus is the perception of sound without an external source. More than 50 million people in the United States have reported experiencing tinnitus, resulting in an estimated prevalence of 10% to 15% in adults. Despite the high prevalence of tinnitus and its potential significant effect on quality of life, there are no evidence-based, multidisciplinary clinical practice guidelines to assist clinicians with management. The focus of this guideline is on tinnitus that is both bothersome and persistent (lasting 6 months or longer), which often negatively affects the patient's quality of life. The target audience for the guideline is any clinician, including nonphysicians, involved in managing patients with tinnitus. The target patient population is limited to adults (18 years and older) with primary tinnitus that is persistent and bothersome. PURPOSE: The purpose of this guideline is to provide evidence-based recommendations for clinicians managing patients with tinnitus. This guideline provides clinicians with a logical framework to improve patient care and mitigate the personal and social effects of persistent, bothersome tinnitus. It will discuss the evaluation of patients with tinnitus, including selection and timing of diagnostic testing and specialty referral to identify potential underlying treatable pathology. It will then focus on the evaluation and treatment of patients with persistent primary tinnitus, with recommendations to guide the evaluation and measurement of the effect of tinnitus and to determine the most appropriate interventions to improve symptoms and quality of life for tinnitus sufferers. ACTION STATEMENTS: The development group made a strong recommendation that clinicians distinguish patients with bothersome tinnitus from patients with nonbothersome tinnitus. The development group made a strong recommendation against obtaining imaging studies of the head and neck in patients with tinnitus, specifically to evaluate tinnitus that does not localize to 1 ear, is nonpulsatile, and is not associated with focal neurologic abnormalities or an asymmetric hearing loss. The panel made the following recommendations: Clinicians should (a) perform a targeted history and physical examination at the initial evaluation of a patient with presumed primary tinnitus to identify conditions that if promptly identified and managed may relieve tinnitus; (b) obtain a prompt, comprehensive audiologic examination in patients with tinnitus that is unilateral, persistent (≥ 6 months), or associated with hearing difficulties; (c) distinguish patients with bothersome tinnitus of recent onset from those with persistent symptoms (≥ 6 months) to prioritize intervention and facilitate discussions about natural history and follow-up care; (d) educate patients with persistent, bothersome tinnitus about management strategies; (e) recommend a hearing aid evaluation for patients who have persistent, bothersome tinnitus associated with documented hearing loss; and (f) recommend cognitive behavioral therapy to patients with persistent, bothersome tinnitus. The panel recommended against (a) antidepressants, anticonvulsants, anxiolytics, or intratympanic medications for the routine treatment of patients with persistent, bothersome tinnitus; (b) Ginkgo biloba, melatonin, zinc, or other dietary supplements for treating patients with persistent, bothersome tinnitus; and (c) transcranial magnetic stimulation for the routine treatment of patients with persistent, bothersome tinnitus. The development group provided the following options: Clinicians may (a) obtain an initial comprehensive audiologic examination in patients who present with tinnitus (regardless of laterality, duration, or perceived hearing status); and (b) recommend sound therapy to patients with persistent, bothersome tinnitus. The development group provided no recommendation regarding the effect of acupuncture in patients with persistent, bothersome tinnitus.

Clinical practice guideline: tinnitus executive summary.

The American Academy of Otolaryngology--Head and Neck Surgery Foundation (AAO-HNSF) has published a supplement to this issue featuring the new Clinical Practice Guideline: Tinnitus. To assist in implementing the guideline recommendations, this article summarizes the rationale, purpose, and key action statements. The 13 recommendations developed address the evaluation of patients with tinnitus, including selection and timing of diagnostic testing and specialty referral to identify potential underlying treatable pathology. It will then focus on the evaluation and treatment of patients with persistent primary tinnitus, with recommendations to guide the evaluation and measurement of the impact of tinnitus and to determine the most appropriate interventions to improve symptoms and quality of life for tinnitus sufferers.

Clinical practice guideline: sudden hearing loss.

OBJECTIVE: Sudden hearing loss (SHL) is a frightening symptom that often prompts an urgent or emergent visit to a physician. This guideline provides evidence-based recommendations for the diagnosis, management, and follow-up of patients who present with SHL. The guideline primarily focuses on sudden sensorineural hearing loss (SSNHL) in adult patients (aged 18 and older). Prompt recognition and management of SSNHL may improve hearing recovery and patient quality of life (QOL). Sudden sensorineural hearing loss affects 5 to 20 per 100,000 population, with about 4000 new cases per year in the United States. This guideline is intended for all clinicians who diagnose or manage adult patients who present with SHL. PURPOSE: The purpose of this guideline is to provide clinicians with evidence-based recommendations in evaluating patients with SHL, with particular emphasis on managing SSNHL. The panel recognized that patients enter the health care system with SHL as a nonspecific, primary complaint. Therefore, the initial recommendations of the guideline deal with efficiently distinguishing SSNHL from other causes of SHL at the time of presentation. By focusing on opportunities for quality improvement, the guideline should improve diagnostic accuracy, facilitate prompt intervention, decrease variations in management, reduce unnecessary tests and imaging procedures, and improve hearing and rehabilitative outcomes for affected patients. RESULTS: The panel made strong recommendations that clinicians should (1) distinguish sensorineural hearing loss from conductive hearing loss in a patient presenting with SHL; (2) educate patients with idiopathic sudden sensorineural hearing loss (ISSNHL) about the natural history of the condition, the benefits and risks of medical interventions, and the limitations of existing evidence regarding efficacy; and (3) counsel patients with incomplete recovery of hearing about the possible benefits of amplification and hearing-assistive technology and other supportive measures. The panel made recommendations that clinicians should (1) assess patients with presumptive SSNHL for bilateral SHL, recurrent episodes of SHL, or focal neurologic findings; (2) diagnose presumptive ISSNHL if audiometry confirms a 30-dB hearing loss at 3 consecutive frequencies and an underlying condition cannot be identified by history and physical examination; (3) evaluate patients with ISSNHL for retrocochlear pathology by obtaining magnetic resonance imaging, auditory brainstem response, or audiometric follow-up; (4) offer intratympanic steroid perfusion when patients have incomplete recovery from ISSNHL after failure of initial management; and (5) obtain follow-up audiometric evaluation within 6 months of diagnosis for patients with ISSNHL. The panel offered as options that clinicians may offer (1) corticosteroids as initial therapy to patients with ISSNHL and (2) hyperbaric oxygen therapy within 3 months of diagnosis of ISSNHL. The panel made a recommendation against clinicians routinely prescribing antivirals, thrombolytics, vasodilators, vasoactive substances, or antioxidants to patients with ISSNHL. The panel made strong recommendations against clinicians (1) ordering computerized tomography of the head/brain in the initial evaluation of a patient with presumptive SSNHL and (2) obtaining routine laboratory tests in patients with ISSNHL.

Induced unilateral vocal fold paralysis and recovery rapidly modulate brain areas related to phonatory behavior: a case study.

BACKGROUND: Peripheral and behavioral effects of voice disorders are well documented in the literature; yet, there is little information regarding the central neural biomarkers and mechanisms underlying these disorders. Understanding the details of brain function changes in disordered voice production is a critical factor for developing better treatment strategies that result in more robust patient outcomes. OBJECTIVE: To examine a model of induced unilateral vocal fold paralysis (iUVFP) to demonstrate and characterize the form of activity changes within central mappings of the larynx to the induced paralysis. The induced paralysis model allowed the participant to serve as his or her own control when comparing baseline results of normal voice with results during the paralysis and subsequent recovery. STUDY DESIGN: Prospective, case-study design. METHODS: Functional magnetic resonance imaging was used to examine central laryngeal representations during three time points: pre-iUVFP, during iUVFP, and postrecovery from iUVFP. iUVFP was induced using a lidocaine with epinephrine nerve block unilaterally. Percent changes in blood oxygenation level-dependent (BOLD) activity served as the dependent variable. RESULTS: Results indicated an overall reduced activity level in sensorimotor, subcortical, and cerebellar regions during paralysis. Recovery from paralysis led to augmented responses, particularly in sensory, association, and cerebellar zones. CONCLUSIONS: The decrease in activity during iUVFP and the significantly increased activity during the recovery phase likely represent immediate neuroplastic events occurring within minutes of nerve blockade. Recovery-related changes in the BOLD response are hypothesized to be associated with a recalibration of the system after return of normal laryngeal function.

Laser projection imaging for measurement of pediatric voice.

OBJECTIVES/HYPOTHESIS: The aim of the study was to present the development of a miniature laser projection endoscope and to quantify vocal fold length and vibratory amplitude of the pediatric glottis using high-speed digital imaging coupled with the laser endoscope. STUDY DESIGN: For this prospective study, absolute measurement of entire vocal fold length, membranous length of the vocal fold, and vibratory amplitude during phonation were obtained in one child (9 years old), one adult male (36 years old), and one adult female (20 years old) with the use of high-speed digital imaging, coupled with a custom-developed laser projection endoscope. METHODS: The laser projection system consists of a module slip-fit sleeve with two 3-mW 650-nm laser diodes in horizontal orientation separated by a distance of 5 mm. Calibration involved projecting the laser onto grid patterns at depths ranging from 6 to 10 cm and tilt angles of 15 to -5 degrees to obtain pixel-to-millimeter conversion templates. Measurements of vocal fold length and vibratory amplitude were extracted based on methods of image processing. RESULTS: The system demonstrated a method for estimating vocal fold length and vibratory amplitude with a single laser point with high measurement precision. First measurements of vocal fold length (6.8 mm) and vibratory amplitude (0.25 mm) during phonation in a pediatric participant are reported. CONCLUSIONS: The proposed laser projection system can be used to obtain absolute length and vibratory measurements of the pediatric glottis. The projection system can be used with stroboscopy or high-speed digital imaging systems with a 70-degree rigid endoscope.

Clinical practice guideline: tonsillectomy in children.

OBJECTIVE: Tonsillectomy is one of the most common surgical procedures in the United States, with more than 530,000 procedures performed annually in children younger than 15 years. Tonsillectomy is defined as a surgical procedure performed with or without adenoidectomy that completely removes the tonsil including its capsule by dissecting the peritonsillar space between the tonsil capsule and the muscular wall. Depending on the context in which it is used, it may indicate tonsillectomy with adenoidectomy, especially in relation to sleep-disordered breathing. This guideline provides evidence-based recommendations on the preoperative, intraoperative, and postoperative care and management of children 1 to 18 years old under consideration for tonsillectomy. In addition, this guideline is intended for all clinicians in any setting who interact with children 1 to 18 years of age who may be candidates for tonsillectomy. PURPOSE: The primary purpose of this guideline is to provide clinicians with evidence-based guidance in identifying children who are the best candidates for tonsillectomy. Secondary objectives are to optimize the perioperative management of children undergoing tonsillectomy, emphasize the need for evaluation and intervention in special populations, improve counseling and education of families of children who are considering tonsillectomy for their child, highlight the management options for patients with modifying factors, and reduce inappropriate or unnecessary variations in care. RESULTS: The panel made a strong recommendation that clinicians should administer a single, intraoperative dose of intravenous dexamethasone to children undergoing tonsillectomy. The panel made a strong recommendation against clinicians routinely administering or prescribing perioperative antibiotics to children undergoing tonsillectomy. The panel made recommendations for (1) watchful waiting for recurrent throat infection if there have been fewer than 7 episodes in the past year or fewer than 5 episodes per year in the past 2 years or fewer than 3 episodes per year in the past 3 years; (2) assessing the child with recurrent throat infection who does not meet criteria in statement 2 for modifying factors that may nonetheless favor tonsillectomy, which may include but are not limited to multiple antibiotic allergy/intolerance, periodic fever, aphthous stomatitis, pharyngitis and adenitis, or history of peritonsillar abscess; (3) asking caregivers of children with sleep-disordered breathing and tonsil hypertrophy about comorbid conditions that might improve after tonsillectomy, including growth retardation, poor school performance, enuresis, and behavioral problems; (4) counseling caregivers about tonsillectomy as a means to improve health in children with abnormal polysomnography who also have tonsil hypertrophy and sleep-disordered breathing; (5) counseling caregivers that sleep-disordered breathing may persist or recur after tonsillectomy and may require further management; (6) advocating for pain management after tonsillectomy and educating caregivers about the importance of managing and reassessing pain; and (7) clinicians who perform tonsillectomy should determine their rate of primary and secondary posttonsillectomy hemorrhage at least annually. The panel offered options to recommend tonsillectomy for recurrent throat infection with a frequency of at least 7 episodes in the past year or at least 5 episodes per year for 2 years or at least 3 episodes per year for 3 years with documentation in the medical record for each episode of sore throat and 1 or more of the following: temperature >38.3°C, cervical adenopathy, tonsillar exudate, or positive test for group A ß-hemolytic streptococcus.

A pharmacokinetic and pharmacodynamic study, in healthy volunteers, of a rapidly absorbed intranasal midazolam formulation.

PURPOSE: To compare 2.5 mg and 5.0 mg single-dose pharmacokinetics (PK), pharmacodynamics (PD) and tolerability of an intranasal (i.n.) midazolam formulation, to a 2.5-mg intravenous (i.v.) dose. METHODS: Design was an open-label, three-way crossover, randomized PK and PD study in seventeen healthy volunteers. Twelve-hour PK parameters were determined for each treatment arm. Subjects completed serial self-ratings for sedation and other drug effects. Nurse observers made serial observations for sedation and adverse effects. An otolaryngologist conducted a nasal endoscopy, pre-dose, 2-4 h, and at end of study, to examine the nasal cavity for formulation-induced changes in nasal anatomy. RESULTS: Midazolam was rapidly absorbed following i.n. administration, with a median t(max) of 10 min; dose proportionate increases for C(max) and AUC; t(1/2) of 4 h; and, 60% (+/-23) nasal administration bioavailability compared to the i.v. dose. PD responses were rapid, paralleled the PK, and in magnitude was in a rank order of i.v. 2.5 mg > or = i.n. 5.0 mg > i.n. 2.5 mg doses. The formulation was well tolerated with no serious cardiovascular or respiratory complications. Fourteen subjects complained of at least one of the following: a brief and mild to moderate intensity facial flushing, nasal passage burning, sore throat or bad taste after drug administration. There were no adverse findings from the nasal endoscopic exam. CONCLUSION: Dosages of an investigational i.n. midazolam formulation resulted in rapid absorption and attained plasma concentrations that correlated with pharmacodynamic effects.

A multiple-dose phase I study of intranasal hydromorphone hydrochloride in healthy volunteers.

We evaluated the pharmacokinetics, tolerability, and safety of 1 and 2 mg of intranasal hydromorphone hydrochloride in an open-label, single- and multiple-dose study. This Phase I study was conducted in 24 healthy volunteers (13 men and 11 women). Intranasal doses were delivered as 0.1-mL metered-dose sprays into one or both nostrils for 1- and 2-mg doses, respectively. Venous blood samples were taken serially from 0 to 12 h after the first single dose and the last (seventh) multiple dose. Plasma hydromorphone concentrations were determined by liquid chromatography/mass spectrometry/mass spectrometry. Noncompartmental analysis was used to estimate pharmacokinetic variables. After 7 intranasal doses of 1 and 2 mg (once every 6 h), mean +/- sd peak plasma concentrations of 2.8 +/- 0.7 ng/mL and 5.3 +/- 2.3 ng/mL, respectively, were observed. The median time to peak concentration was 20 min for both single and multiple doses. Dose proportionality was observed for the 1- and 2-mg doses. Adverse events included somnolence, dizziness, and bad taste after dose administration. Intranasal hydromorphone hydrochloride was well tolerated and demonstrated rapid nasal drug absorption and predictable accumulation. These results support clinical investigation of hydromorphone hydrochloride nasal spray for use as an alternative to oral and IM administration.

Pharmacokinetics and bioavailability of single-dose intranasal hydromorphone hydrochloride in healthy volunteers.

UNLABELLED: We evaluated pharmacokinetics and absolute bioavailability of single doses of hydromorphone hydrochloride after administration of 1.0 and 2.0 mg of intranasal (IN) and 2.0 mg of IV hydromorphone hydrochloride. An open-label, randomized, three-way crossover study was conducted in 24 healthy volunteers (13 men and 11 women). IN doses were delivered as 0.1-mL metered-dose sprays into one or both nostrils for 1.0- and 2.0-mg doses, respectively. Blood samples were taken serially from 0 to 16 h after each dose. Plasma hydromorphone concentrations were determined by liquid chromatography-mass spectrometry-mass spectrometry. Noncompartmental analysis was used to estimate pharmacokinetic variables. Mean hydromorphone bioavailabilities and percent coefficient of variation of 52.4% (22.7) and 57.5% (18.6) were seen after the 1.0- and 2.0-mg IN doses, respectively. Median times to maximum concentration were 20 and 25 min for IN doses. Adverse events included somnolence and dizziness with all routes of administration and a bad taste after IN doses. Dose proportionality for the 1.0- and 2.0-mg IN doses was observed. IN hydromorphone hydrochloride met the minimum requirements for safety and demonstrated rapid nasal drug absorption and clinically relevant bioavailability. Results support further development of this novel hydromorphone hydrochloride nasal spray. IMPLICATIONS: Pharmacokinetics and bioavailability were determined for two doses of intranasal hydromorphone in healthy volunteers. Rapid, reliable absorption, and predictable pharmacokinetics support the investigation of hydromorphone hydrochloride nasal spray as a therapeutic alternative to oral and IM administration.