What are the typical symptoms of GERD?
Heartburn is usually characterized as a midline retrosternal burning sensation that radiates to the throat and, occasionally, to the intrascapular region. Patients often place the open hand over the sternal area and flip the wrist in an up-and-down motion to simulate the nature and location of the heartburn symptoms. Mild symptoms of heartburn are often relieved within 3-5 minutes of ingesting milk or antacids. Other symptoms of GERD include the following:

1. Regurgitation consists of eructation of gastric juice or stomach contents into the pharynx and is often accompanied by a noxious bitter taste. Regurgitation is most common after a large meal and occurs usually with stooping or assuming a recumbent posture.
2. Dysphagia (difficulty in swallowing) is usually caused by a benign stricture of the esophagus in patients with long-standing GERD. Solid foods, such as meat and bread, are often precipitants of dysphagia. Dysphagia implies significant narrowing of the esophageal lumen, to usually a luminal diameter <13 mm. Prolonged dysphagia, associated with inability to swallow saliva, requires prompt evaluation and often endoscopic removal.
3. Waterbrash is an uncommon symptom but highly suggestive of GERD. Patients literally foam at the mouth because the salivary glands produce up to 10 mL/min of saliva as an esophagosalivary reflex response to acid reflux.

Is gastrointestinal (GI) hemorrhage a common symptom of GERD?
No. Endoscopic evaluation of patients with upper GI hemorrhage has identified erosive GERD as the cause in only 2-6% of cases.

What is odynophagia? Is it a common symptom of GERD?
Odynophagia is a painful substernal sensation associated with swallowing that should not be confused with dysphagia. Odynophagia rarely results from GERD. Instead, odynophagia is caused by infections (monilia, herpes simplex virus, and cytomegalovirus), ingestion of corrosive agents or pills (tetracycline, vitamin C, iron, quinidine, estrogen, aspirin, alendronate [Fosamax], or nonsteroidal anti-inflammatory drugs), or cancer.

What clues about GERD can be gleaned from the physical exam?

1. Severe kyphosis is often associated with hiatal hernia and GERD, especially when a body brace is necessary.
2. Tight-fitting corsets or clothing (in men or women) can increase intra-abdominal pressure and may cause stress reflux.
3. Abnormal phonation may suggest high GERD and vocal cord injury. When hoarseness is due to high GERD, the voice is often coarse or gravelly and may be worse in the morning, whereas in other causes of hoarseness, excessive voice use or abuse leads to worsening later in the day.
4. Wheezing or asthma and pulmonary fibrosis have been associated with GERD. Patients often give a history of postprandial or nocturnal regurgitation with episodes of coughing or choking caused by near or partial aspiration.
5. Loss of enamel on the lingual surface of the teeth may be seen in severe GERD, although it is more common in patients with rumination syndrome or bulimia.
6. Esophageal dysfunction may be the predominant component of scleroderma or mixed connective tissue disease. Inquiry about symptoms of Raynaud’s syndrome and examination for sclerodactyly, taut skin, and calcinosis are important.
7. Cerebral palsy, Down syndrome, and mental retardation are commonly associated with GERD.
8. Children with peculiar head movements during swallowing may have Sandifer’s syndrome.
9. Some patients unknowingly swallow air (aerophagia) that triggers a burp, belch, and heartburn cycle.

The observant clinician may detect this behavior during the interview and physical exam.

Do healthy persons have GERD?
Yes. Healthy persons may regurgitate acid or food contents into the esophagus, especially after a large meal late at night. In normal persons, the natural defense mechanisms of the lower esophageal sphincter barrier and esophageal clearance are not overwhelmed, hence symptoms and injury do not occur. Ambulatory esophageal pH studies have shown that healthy persons have acid reflux into the esophagus <2% of the daytime (upright position) and <0.3% of the nighttime (supine position).

How can swallowing and salivary production be associated with GERD?
Reflux of gastric contents into the esophagus often stimulates salivary production and increased swallowing. Saliva has a neutral pH, which helps to neutralize the gastric refluxate. Furthermore, the swallowed saliva initiates a peristaltic wave that strips the esophagus of refluxed material (clearance). During the awake upright period, persons swallow 70 times/h; this rate increases to 200 times/h during meals. Swallowing is least common during sleep (<10 times/h), and arousal from sleep to swallow during GERD may be reduced by sedatives or alcohol ingestion. Patients with Sjögren’s syndrome and smokers have reduced salivary production and prolonged esophageal acid clearance times.
What clearance defects are associated with GERD?

1. Esophageal. Normally, reflux of gastric contents into the esophagus stimulates a secondary peristaltic or clearance wave to remove the injurious refluxate from the esophagus. The worst case of ineffective esophageal clearance is seen in patients with scleroderma. The lower esophageal sphincter barrier is nonexistent, and there is no primary or secondary peristalsis of the esophagus (hence, no clearance).
2. Gastric. Gastroparesis may lead to excessive quantities of retained gastroduodenal and food contents. Larger volumes of stagnant gastric contents predispose to esophageal reflux.

How may the gastroesophageal (GE) barrier be compromised?
The normal lower esophageal sphincter (LES) is 3-4 cm long and maintains a resting tone of 10-30 mmHg pressure. The LES acts as a barrier against GERD. When the LES pressure is <6 mmHg, GERD is common; however, the presence of “normal” LES pressure does not predict absence of GERD. In fact, LES pressure <10 mmHg is found in a minority of people with GERD. Recent studies have shown that transient LES relaxations (tLESRs) are important in the pathogenesis of GERD. During tLESR, the sphincter inappropriately relaxes and free gastric reflux occurs.

What other medical conditions may mimic symptoms of GERD?
The differential diagnosis of GERD includes coronary artery disease, gastritis, gastroparesis, infectious and pill-induced esophagitis, peptic ulcer disease, biliary tract disease, and esophageal motor diseases.

How can GERD be distinguished from coronary artery disease?
In the evaluation of patients with retrosternal chest pain, the clinician must always be mindful that patients with GERD do not die, but patients with new-onset angina or an acute myocardial infarction with symptoms mimicking GERD can. Clues that a patient’s chest pain is cardiac in origin include radiation of the pain to the neck, jaw, or left shoulder/upper extremity; associated shortness of breath and/or diaphoresis; precipitation of pain by exertion; and relief of pain with sublingual nitroglycerin. Physical findings of new murmurs or gallops or abnormal rhythms are also suggestive of a cardiac origin. Although positive findings on an electrocardiogram (ECG) are helpful in the evaluation of patients with chest pain, the absence of ischemic ECG changes should not discourage the clinician from excluding a cardiac etiology for the patient’s symptoms.

How should patients with symptoms of GERD be evaluated?
Evaluation of patients with GERD may be guided by the severity of symptoms. Patients without symptoms of high GERD (aspiration or hoarseness) or dysphagia may be given careful instruction about lifestyle modification and a diagnostic trial of H2-blocker therapy and followed clinically. Diagnostic evaluation is warranted when symptoms of GERD are chronic or incompletely responsive to medical therapy. Esophagogastroduodenoscopy (EGD) is the single best test for evaluation of GERD. Up to 50% of patients with GERD do not have macroscopic evidence of esophagitis at the time of endoscopy. In this group, more sensitive GER testing may be necessary or alternative diagnoses considered.

What are the more sophisticated esophageal function tests? How can they be used appropriately in the evaluation of patients with GERD?
Clinical tests of GERD may be divided into three categories:

• Acid sensitivity
  Acid perfusion (Bernstein) test
  24- to 48-hour ambulatory esophageal pH monitoring
• Esophageal barrier and motility
  Esophageal manometry
  Gastroesophageal scintiscanning
  Standard acid reflux (modified Tuttle) test
  24- to 48-hour ambulatory esophageal pH monitoring
• Esophageal acid clearance time
  Standard acid reflux clearance test (SART)
  24- to 48-hour ambulatory esophageal pH monitoring

Do all patients with GERD need esophageal function testing?
No. Testing should be reserved for patients who fail medical therapy or in whom the correlation of reflux symptoms is in doubt.

When is ambulatory esophageal pH monitoring helpful?
Ambulatory esophageal pH monitoring is helpful in evaluating patients refractory to standard medical therapy. Acid hypersecretion is often seen in patients with GERD, and esophageal pH monitoring may be helpful in titrating the dose of H2-blocker or proton pump inhibitor (PPI). Persistence of acid reflux on “adequate” doses of a PPI should raise the possibility of patient noncompliance or Zollinger-Ellison syndrome.
The Bravo capsule (Medtronix, Inc., Minneapolis, MN) is a new wireless technology that permits more physiologic intraesophageal monitoring for acid reflux. The Bravo capsule is the size of a gel cap and placed with or without endoscopic assistance 6 cm above the squamocolumnar junction. The capsule is “stapled” to the esophageal mucosal permitting more physiologic and prolonged intra-esophageal monitoring. Some investigators have begun to “staple” the capsule in the proximal esophagus to evaluate patients with atypical reflux symptoms, such as hoarseness, throat tightness, asthma, and interstitial lung disease.

When are esophageal manometry and scintiscanning helpful?
Esophageal manometry is helpful in evaluating the competency of the LES barrier and the body of the esophagus for motor dysfunction. Severe esophagitis may be the sole manifestation of early scleroderma. When ambulatory pH testing is not available, scintiscanning has been shown to be helpful.

What are some of the new endoscopic treatments for GERD?

1. Endoluminal gastroplication (ELGP): Endocinch by CR Bard, Inc., or Endoscopic Suturing Device by Wilson Cook, Inc.
2. Single full-thickness plication: NDO Endoplication System by NDO Surgical, Inc. (not FDA approved)
3. Coagulation injury: Stretta by Curon Medical, Inc.
4. Polymer injection: Enteryx by Boston Scientific Corp.

What is Barrett’s esophagus? How is it managed?
Barrett’s esophagus is a metaplastic degeneration of the normal esophageal lining, which is replaced with a premalignant, specialized columnar epithelium. It is seen in roughly 5-7% of patients with uncomplicated reflux but in up to 30-40% of patients with scleroderma or dysphagia.
Currently, there is no proven method to eliminate Barrett’s esophagus. Preliminary studies of laser or bicap ablation of the metaplastic segment followed by alkalization of the gastroesophageal refluxate are encouraging. The need for cancer surveillance is discussed elsewhere in this book.

Is there an association between obstructive sleep apnea (OSA) and GERD?
Yes. Nocturnal acid reflux is seen in 54-72% of persons with OSA. Administration of nighttime continuous positive airway pressure (CPAP) and/or proton pump inhibitor therapy have been shown to decrease apnea and acid reflux events.

Does the presence of heartburn symptoms predict a GERD-related cough etiology?
No. There is poor correlation between symptoms of heartburn and cough. Between 43% and 75% of patients with GERD-related cough do not have heartburn symptoms. Both medical treatment with PPIs and surgical antireflux procedures have been reported to be effective for GERD-related cough. Caveats include:

• 35% response rate to omeprazole 40 mg two times/day after 2 weeks
• Results of surgical antireflux procedures are best when preoperative esophageal manometry is normal and response to PPI is positive.

What is the best method to evaluate for possible GERD-related cough?
The first step is to exclude non-GERD-related etiologies: angiotensin-converting inhibitors, environmental irritants, smoking, parenchymal lung disease, allergic rhinitis and pneumonitis, and asthma and sinusitis, which are often “silent.” Symptom relief after a 2-week trial of Prilosec (or equivalent), 40 mg two times/day, is a cost-effective approach. Patients who do not respond should be considered for further evaluation, including esophageal manometry/pH testing and/or EGD.

What is the most efficient, cost-effective method to evaluate hoarse patients for EPR?
The first step in the evaluation of hoarseness should be exclusion of structural ear, nose, and throat (ENT) disorders, including neoplasm. The next step is an empiric trial of double-dose PPI for 2-3 months. Most EPR-related hoarseness improves with acid suppression (60-96%). Patients responding to PPIs may stop the medication and be monitored for recurrence of symptoms. Hoarse patients with a negative ENT evaluation, who fail PPI therapy, should undergo formal esophageal pH analysis.

Can gastroesophageal reflux worsen asthma?
Yes. Numerous studies have shown that reflux symptoms are common among asthmatics (65-72%) and that medical and surgical antireflux treatment may improve pulmonary function.

How does gastroesophageal reflux worsen asthma?
Several mechanisms are theorized to explain GERD-induced bronchospasm:

• Asthmatics with GERD have been shown to have autonomic dysregulation with heightened vagal response, which is presumed to be responsible for the decrease in LES pressure and more frequent transient relaxations of the LES, which promote reflux.
• Esophageal reflux may incite a vagal-mediated esophagobronchial reflex of airway hyperreactivity.
• Microaspiration of gastric juice has been shown to activate a local axonal reflex involving release of substance P, which leads to airway edema. The finding of lipid-laden alveolar macrophages among asthmatics demonstrates aspiration of gastric material into the pulmonary tree.

Which patients with GERD should be considered for a surgical antireflux procedure?
Any young, healthy patient with chronic GERD requiring lifelong PPI medical therapy may be considered for an antireflux procedure. Other indications include failed medical therapy, complicated GERD (e.g., bleeding, recurrent strictures), medical success at excessive cost in young, otherwise healthy patients, and problematic symptoms due to regurgitation (asthma, hoarseness, cough).

What is the best endoscopic or surgical antireflux procedure?
Rapid advances in endoscopic and laparoscopic surgery make this question unanswerable. Novel endoscopic suturing, burning, and injection techniques are exciting, but results are only preliminary. A comparative trial of endoscopic and surgical antireflux techniques is necessary.

What cytochrome p-450 (CYP-450) systems are involved in the metabolism of PPIs?
All of the PPIs undergo some hepatic metabolism through the CYP-450 system. The CYP-2C19 and CYP-3A4 microsomal enzymes are responsible for the majority of PPI hepatic metabolism. Genetic polymorphism with CYP-2C19 is common; about 5% of Americans and 20% of Asians are deficient in this enzyme. Omeprazole decreases the metabolism of phenytoin and warfarin R-isomer (CYP-2C9), diazepam (CYP-2C19), and cyclosporine (CYP-3A4).

How do esomeprazole (Nexium) and omeprazole (Prilosec) differ?
Omeprazole is a racemic mixture of both the S- and R-isomers, whereas esomeprazole is a “pure” form of the S-isomer. Less esomeprazole (S-isomer) is metabolized by the CYP-2C19 pathway, leading to greater area under the curve and better intragastric acid suppression for 24 hours. Esomeprazole is the only PPI shown to be statistically superior to omeprazole in healing erosive esophagitis at 8 weeks (90-94% efficacy rate).

Date Last Modified: March 21, 2010

References
WEBSITES

http://www.endocinch.com/

BIBLIOGRAPHY

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2. DeVault KR: Overview of therapy for the extraesophageal manifestations of gastroesophageal reflux disease. Am J Gastroenterol 95:S39-S44, 2000.
3. Gistout CJ. Endoscopic Antireflux. Visible Human Journal of Endoscopy (VHJOE). 2003;2:3:4. (http://www.vhjoe.com/Volume2Issue3/2-3-4.htm)
4. Green BT, Broughton WA, O’Connor JB: Marked improvement in nocturnal gastroesophageal reflux in a large cohort of patients with obstructive sleep apnea treated with continuous positive airway breathing. Arch Intern Med 163:41-45, 2003.
5. Harding SM, Sontag SJ: Asthma and gastroesophageal reflux. Am J Gastroenterol 95:S23-S32, 2000.
6. Irwin RS, Richter JE: Gastroesophageal reflux and chronic cough. Am J Gastroenterol 95:S9-S14, 2000.
7. Kellog TA, Oelschlanger BK, Pellegrini CA: Laparoscopic antireflux surgery. VHJOE 2:3, 2003. (http://www.vhjoe.com/Volume2Issue3/2-3-3.htm)
8. Lazarchick DA, Filler SJ: Dental erosion: Predominant oral lesion in gastroesophageal reflux disease. Am J Gastroenterol 95:S33-S38, 2000.
9. McNally PR: Eosinophilic esophagitis. VHJOE 3:1, 2004.
10. McNally PR, Maydonovitch CL, Prosek RA, et al: Evaluation of gastroesophageal reflux as a cause of idiopathic hoarseness. Dig Dis Sci 34:1900-1904, 1989.
11. Meier JH, McNally PR, Freeman SR, et al: Does omeprazole (Prilosec) improve asthma in patients with gastroesophageal reflux: A double blind crossover study. Dig Dis Sci 39:1900-1904, 1994.
12. Richter JE: Extraesophageal presentations of gastroesophageal reflux disease: An overview. Am J Gastroenterol 95:S1-S3, 2000.
13. Senior BA, Khan M, Schwimmer C, et al: Gastroesophageal reflux and obstructive sleep apnea. Laryngoscope 111:2144-2146, 2001.
14. Spencer CM, Faulds D: Esomeprazole. Drugs 60:321-327, 2000.
15. Tutuian R, Castell DO: Use of multichannel intraluminal impedance to document proximal esophageal and pharyngeal nonacidic reflux episodes. Am J Med 115(Suppl 3A):119S-123S, 2003.
16. Ward EM, Devault KR, Bouras EP, et al: Successful oesophageal pH monitoring with a catheter-free system. Aliment Pharmacol Ther 19:449-454, 2004.
17. Wong RKH, Hanson DG, Waring PJ, Shaw G: ENT manifestations of gastroesophageal reflux. Am J Gastroenterol 95:S15-S22, 2000.

What sensory cues elicit swallowing?
The sensory cues are not entirely known, but entry of food or fluid into the hypopharynx, specifically the sensory receptive field of the superior laryngeal nerve, is paramount. Swallowing may also be initiated by volitional effort, if food is present in the oral cavity. The required signal for initiation of the swallow response is a mixture of both peripheral sensory input from oropharyngeal afferents and superimposed control from higher nervous system centers. Neither is capable of initiating swallowing independent of the other. Thus, swallowing cannot be initiated during sleep when higher centers are turned off or with deep anesthesia to the oral cavity when peripheral afferents are disconnected.

What is flexible endoscopic evaluation of swallowing with sensory testing (FEESST)?
FEESST is an endoscopic test that allows direct visualization of the hypopharynx and larynx during swallowing evaluation. It can directly assess airway protection during a swallow. A thin, flexible endoscope is passed transnasally into the hypopharynx. Pooling of hypopharyngeal secretions is recorded and is used to gauge aspiration risk. Next, swallowing assessment is done with liquids (mixed with food coloring) of varying consistency, given serially to the patient and observed as they traverse the hypopharynx. Any penetration into the larynx (aspiration) is noted. Finally, discrete pulses of air are given, endoscopically, to the mucosa innervated by the superior laryngeal nerve to elicit the protective laryngeal adductor reflex. This results in brief closure of the vocal cords with or without a swallow. An intact reflex supports a low aspiration risk. FEESST is a safe procedure that can be performed at the bedside or office, and it does not require sedation.

What is the difference between globus sensation (globus hystericus) and dysphagia?
Globus sensation is the feeling of a lump in the throat. It is present continually and is not related to swallowing. It may even be temporarily alleviated during a swallow. Dysphagia is difficulty in swallowing and is noted by the patient only during swallowing.

Do patients accurately localize the site of dysphagia?
No. Patients with esophageal dysphagia localize the abnormal site correctly only 60-70% of the time. Patients incorrectly localize the site of dysphagia proximal to the actual site in the remainder. Differentiating between proximal and distal lesions may be difficult, based on the patient’s perception only. Patients with oropharyngeal dysphagia usually recognize that the swallow dysfunction is in the oropharynx. They may perceive food accumulating in the mouth or an inability to initiate a pharyngeal swallow. They can generally recognize aspiration before, during, or after a swallow. Associated symptoms, such as difficulty with chewing, drooling, coughing or choking after a swallow, are more suggestive of oropharyngeal than esophageal dysphagia.

What symptoms can be seen in oropharyngeal dysphagia?

• Inability to initiate a swallow
• Sensation of food getting stuck in the throat
• Coughing or choking (aspiration) during swallowing
• Nasopharyngeal regurgitation
• Changes in speech or voice (nasality)
• Ptosis
• Photophobia or visual changes
• Weakness, especially progressive toward the end of the day

What are the causes of oropharyngeal dysphagia?
Oropharyngeal dysphagia can result from propulsive failure or structural abnormalities of either the oropharynx or esophagus. Propulsive abnormalities can result from dysfunction of the central nervous system control mechanisms, intrinsic musculature, or peripheral nerves. Structural abnormalities may result from neoplasm, surgery, trauma, caustic injury, or congenital anomalies. If dysphagia occurs in the absence of radiographic findings, motor abnormalities may be demonstrable by more sensitive methods, such as electromyography or nerve stimulation studies. If all studies are normal, impaired swallowing sensation may be the primary abnormality

What causes oropharyngeal dysphagia in the elderly?

1. 80% caused by neuromuscular disorders: Leading cause is cerebrovascular accidents (CVAs); others include Parkinson’s disease, myasthenia gravis, and dermatomyositis.
2. 20% caused by structural disorders: Cancer is the most worrisome cause.

Why is a brain stem stroke more likely to cause severe oropharyngeal dysphagia than a hemispheric stroke?
The swallowing center is situated bilaterally, in the reticular substance below the nucleus of the solitary tract, in the brain stem. Efferent fibers from the swallow centers travel to the motor neurons controlling the swallow musculature located in the nucleus ambiguus. Therefore, brain stem strokes are more likely to cause the most severe impairment of swallowing with difficulty in initiating a swallow or absence of the swallow response.

When is it appropriate to evaluate stroke-related dysphagia?
About 25-50% of strokes will result in oropharyngeal dysphagia. Most stroke-related swallowing dysfunction improves spontaneously within the first 2 weeks. Unnecessary diagnostic or therapeutic procedures, such as percutaneous gastrostomy, should be avoided immediately after a cerebrovascular accident. When symptoms persist beyond the 2-week period, swallowing function should be evaluated.

Is a barium swallow examination adequate to evaluate oropharyngeal dysphagia?
No. A barium swallow focuses on the esophagus, is done in a supine position, and takes only a few still images as the barium passes through the oropharynx. Therefore, aspiration may be missed if a conventional barium swallow is ordered.
Oropharyngeal dysphagia is best evaluated with a cineradiographic or videofluoroscopic swallowing study, commonly called the modified barium swallow. The oropharyngeal swallow is rapid and transpires in less than 1 second, images must be obtained and recorded at a rate of 15-30/sec to capture adequately the motor events. The recorded study can be played back in slow motion for careful evaluation. This study is done with the patient in the upright position and resembles normal eating position more than the conventional barium swallow.

Can childhood polio cause dysphagia to develop years later in adulthood?
Yes, even if the initial presentation did not include bulbar involvement. The post polio syndrome is a disorder of the medullary motor neuron resulting from new or continuing instability of previously injured motor neurons. Typically, the syndrome consists of new musculoskeletal symptoms, such as weakness and atrophy in previously affected muscles. Patients become symptomatic 25-35 years after the original illness, and even muscular units (limb or bulbar) that appeared untouched in the original infection may develop signs of clinical weakness. Bulbar neuron involvement was reported previously in only 15% of patients with the acute infection. Recent studies demonstrate that some bulbar muscle dysfunction can be demonstrated in all patients with post polio syndrome, although few report dysphagia. Swallowing problems are most severe in patients with bulbar involvement at the onset.

What is the characteristic feature of dysphagia in myasthenia gravis?
Myasthenia gravis is an autoimmune disorder characterized by progressive destruction of acetylcholine receptors at the neuromuscular junction. It affects the striated portion of the esophageal musculature. A distinct feature is increased muscle weakness with repetitive muscle contraction, such that dysphagia worsens with repeated swallows or as the meal progresses. Resting to allow reaccumulation of acetylcholine in nerve endings improves pharyngoesophageal functions and symptoms simultaneously. Muscles of facial expression, mastication, and swallowing are frequently involved, and dysphagia is a prominent symptom in more than one third of cases. An anticholinesterase antibody test is about 90% sensitive in diagnosing myasthenia gravis. If clinical suspicion is strong, a therapeutic trial with an acetylcholinesterase inhibitor, such as Tensilon, or a cholinomimetic, such as Mestinon, should be considered even in the absence of the anticholinesterase antibody.

What is a Zenker’s diverticulum?
A diverticulum of the hypopharynx. It is located posteriorly in an area of potential weakness at the intersection of the transverse fibers of the cricopharyngeus and the obliquely oriented fibers of the inferior pharyngeal constrictors, also called the Killian’s dehiscence.

Is a Zenker’s diverticulum the result of an obstructive or propulsive defect?
Obstructive defect. Previously, it was believed that the pathogenesis of the diverticulum was due to abnormally high hypopharyngeal pressures caused by defective coordination of upper esophageal sphincter (UES) relaxation during pharyngeal bolus propulsion. It is now known that Zenker’s diverticulum is caused by a constrictive myopathy of the cricopharyngeus (poor sphincter compliance). Increased resistance at the cricopharyngeus and increased intrabolus pressures above this relative obstruction cause muscular stress in the hypopharynx with herniation and diverticulum formation. Thus, Zenker’s diverticulum is an obstructive rather than propulsive disease.

What therapies can be used to improve swallowing?
The goal of swallow therapy is to help minimize the risk of aspiration and to optimize oral delivery of nutrition.
Direct swallow therapies attempt to improve the swallow physiology. Examples include treatment of the primary disease, oral and maxillofacial prosthetics, cricopharyngeal myotomy, and swallow maneuvers, such as the supraglottic swallow.
Compensatory techniques help elimiate symptoms but do not change the swallowing dysfunction. They include adjustment of the patient’s head and neck, changing food viscosity, and optimizing the volume and rate of food delivery.
Indirect swallow therapies address the neuromuscular coordination needed for swallowing. Examples include exercise regimens for tongue coordination and chewing.

Which patients are ideal candidates for swallow therapy?
Patients who are mentally competent and motivated have the best results with swallow therapy. Therapy is most effective for aspiration (during and after swallow) and unilateral pharyngeal paresis.

What are the etiologies of dysphagia in gastroesophageal reflux disease?

1. Inflammation: 30% of patients with esophagitis experience dysphagia.
2. Stricture: dysphagia occurs when the lumen diameter is less than 11-13 mm.
3. Peristaltic dysfunction: this is seen with advanced disease.
4. Hiatus hernia: up to 30% of patients with a hiatus hernia may have dysphagia.

When is botulinum toxin (BTX) used for dysphagia?
BTX has been best studied in dysphagia due to achalasia. Achalasia is caused by selective loss of inhibitory neurons at the LES, resulting in unopposed (tonic) excitation of the LES. BTX injection into the distal esophagus can reduce LES pressure by blocking acetylcholine release from the presynaptic cholinergic nerve terminals in the myenteric plexus. Surgical myotomy is the definitive treatment for achalasia, because repeated BTX therapy is required to maintain efficacy. Ideal candidates for BTX are the elderly and those at high operative risk.
Surgical cricopharyngeal myotomy is the treatment of choice for Zenker’s diverticulum. Endoscopic injection of BTX into the diverticular spur, as an alternative to surgery, has shown favorable results in case reports. BTX in Parkinson’s disease with dysphagia, due to impaired relaxation of the UES, has also shown marked improvement by videofluoroscopic and electromyographic studies. Potential side effects include persistent stenosis and the risk of local BTX diffusion into the larynx or hypopharynx.

Last updated: March 15, 2010

Reference:

• Aviv JE, Kaplan ST, Thomson JE, et al: The safety of flexible endoscopic evaluation of swallowing with sensory testing (FEESST): An analysis of 500 consecutive evaluations. Dysphagia 15(1):39-44, 2000.
• Cook IJ, Gabb M, Panagopoulos V, et al: Pharyngeal (Zenker’s) diverticulum is a disorder of upper esophageal sphincter opening. Gastroenterology 103:1229-1235, 1992.
• Cook IJ, Kahrilas PJ: AGA technical review of management of oropharyngeal dysphagia. Gastroenterology 116:455-478, 1999.
• Kahrilas PJ, Logemann JA, Lin S, Ergun G: Pharyngeal clearance during swallowing: A combined manometric and videofluoroscopic study. Gastroenterology 103:128-136, 1992.
• Kolbasnik J, Waterfall WE, Fachnie B: Long term efficacy of botulinum toxin in classical achalasia: A prospective study. Am J Gastroenterol 94:3434-3439, 1999.
• Ramsey DJ, Smithard DG, Kalra L: Early assessment of dysphagia and aspiration risk in acute stroke patients. Stroke 34(5):1252-1257, 2003.
• Restivo DA, Palmeri A, Marchese-Ragona R: Botulinum toxin for cricopharyngeal dysfunction in Parkinson’s disease. N Engl J Med 346(15):1174-1175, 2002.
• Sonies BC, Dalakas MC: Dysphagia in patients with the post-polio syndrome. N Engl J Med 324:1162-1167, 1991.
• Spechler S: American Gastroenterological Association technical review on treatment of patients with dysphagia caused by benign disorders of the distal esophagus. Gastroenterology 117(1):229-233, 1999.
• Spinelli P, Ballardini G: Botulinum toxin type A (Dysport) for the treatment of Zenker’s diverticulum. Surg Endosc 17(4):660, 2003.

When and how did EBM first develop?
The roots of EBM date to the late 1970s, when a group of clinical epidemiologists, led by David Sackett and his colleagues at McMaster University, began preparing a series of articles advising clinicians how to read clinical journals and apply evidence from the literature to direct patient care.

Who first used the term evidence-based medicine?
The term was first used by Gordon Guyatt, MD, in 1990 while serving as residency director of the internal medicine program at McMaster.

What constitutes the evidence in EBM?
In EBM, any empirical observation about the relationship between event and clinical outcome constitutes potential evidence. Nonetheless, all evidence should not be viewed as equal in making clinical decisions.

What is the hierarchy of evidence used in EBM?
The strength of evidence provided by the unsystematic observations of an individual clinician should not be viewed the same as the evidence provided by systematic and controlled clinical trials. An example of a hierarchy of strength of evidence for treatment decisions is listed, from most preferable to least, as follows:

• N of 1 randomized controlled trials
• A systematic review of randomized controlled trials
• A single randomized trial
• A systematic review of observation studies
• A single observational study
• Physiologic studies
• An unsystematic clinical observation

Guyatt GH, Haynes B, Jaeschke R, et al: Introduction: The philosophy of evidence-based medicine. In Guyatt GH, Rennie D (eds): Users’ Guides to the Medical Literature: A Manual for Evidence-Based Clinical Practice. Chicago, American Medical Association, 2002, pp 5-20.

How does the hierarchy of evidence rank randomized controlled studies versus observational studies? How does it rank multiple studies versus single studies?
The hierarchy demonstrates that, in general, the strength of evidence increases with randomized controlled studies, compared with observational studies. The hierarchy also demonstrates that the strength of evidence increases with multiple studies, compared to individual studies.

What must clinicians remember when generalizing results from studies to individual patients?
When considering available research evidence in making decisions about the treatment of their patients, clinicians most often generalize results from studies of other people, which can weaken causal inferences about treatment effectiveness; clinicians must remember that there are still important questions to be answered about the applicability of research findings from the study group to the treatment of an individual patient outside the study.

How is the N of 1 randomized controlled trial conducted?
An individual patient undergoes pairs of treatment periods: the patient receives an experimental treatment in one period of each of the paired treatment periods and a placebo or alternative treatment in the other period. If feasible, the clinician and patient are blinded to the allocation of treatment and the order of treatment is randomized. Typically, clinicians and patients make quantitative ratings of outcomes, and treatment periods are then alternated until the clinician and the patient are convinced that the patient is, or is not, receiving benefit from the experimental treatment.

What are the strengths and weaknesses of N of 1 randomized controlled clinical trials?
The strengths are that they provide definitive evidence of effectiveness in individual patients, they are feasible, and they can lead to long-term changes in treatment administration and effects.
Weaknesses include the fact that such trials require a high degree of interest, time, and cooperation between clinician and patient. N of 1 trials are not usually appropriate for short-term problems, therapeutic cures, determining long-term outcomes, or disorders that are rare.
Guyatt GH, Keller JL, Jaeschke R, et al. The n-of-1 randomized control trial: Clinical usefulness. Our three-year experience. Ann Intern Med 112:293-299, 1990.
Mahon J, Laupacis A, Donner A, Wood T: Randomised study of n of 1 trials versus standard practice. BMJ 312:1069-1074, 1996.

What is the difference between background and foreground questions in EBM?
One of most difficult aspects of applying EBM to clinical practice is formulating answerable clinical questions for which there are best current evidence available. EBM considers clinical questions in two broad categories: background and foreground questions. Background questions ask for general knowledge about a disorder and attempt to answer the who, what, when, where, why, and how of the disorder or an aspect of the disorder. Foreground questions ask for specific information about managing patients with a disorder and typically ask about the patient, the problem, interventions, and clinical outcomes. Generally, as experience with a disorder increases, the clinician moves from asking a preponderance of background questions to foreground questions.

What are the best sources for finding current best evidence?
Electronic evidence databases, evidence-based journals, and online services are sources that provide significant current best evidence. These sources sharply contrast traditional medical textbooks, which are often not the most appropriate method of finding current best evidence. Although most medical textbooks often provide useful information on pathophysiology, they typically become quickly out-of-date with regard to information on cause, diagnosis, prognosis, prevention, and treatment of a given disorder.

List some online resources that are particularly useful for evidence-based medicine.
ONLINE RESOURCES PARTICULARLY USEFUL FOR EVIDENCE-BASED MEDICINE
ACP Journal Club http://www.acpjc.org
ACP Medicine http://www.acpmedicine.com
Best Bets http://www.bestbets.org/
Centre for Evidence-Based Medicine http://www.cebm.net/index.asp
Clinical Evidence http://www.clinicalevidence.org/
Clinical practice guidelines http://www.guidelines.gov
Cochrane Library http://www3.interscience.wiley.com/cgi-bin/mrwhome/106568753/HOME
emedicine http://www.emedicine.com
Evidence-Based Medicine Reviews (OVID) http://www.ovid.com
Evidence-Based http://cebm.jr2.ox.ac.uk
Harrisons Online http://www.harrisonsonline.com
London Links journal listings http://www.londonlinks.ac.uk
MD Consult http://www.mdconsult.com
Medical Matrix http://www.medmatrix.org
Medline/PubMed http://www.pubmed.gov
Medscape http://www.medscape.com
ScHarr Netting the Evidence http://www.shef.ac.uk/~scharr/ir/netting
United Health Foundation http://www.unitedhealthfoundation.org
UpToDate http://www.uptodate.com
WebMD http://www.webmd.com

Last updated: March 15, 2010
Reference:
1. Dalla Vecchia LK, Grosfeld JL, West KW, et al: Intestinal atresia and stenosis: A 25-year experience with 277 cases. Arch Surg 133:490-496, 1998.
2. Guyatt GH, Haynes B, Jaeschke R, et al: Introduction: The philosophy of evidence-based medicine. In Guyatt GH, Rennie D (eds): Users’ Guides to the Medical Literature: A Manual for Evidence-Based Clinical Practice. Chicago, American Medical Association, 2002, pp 5-20.
3. Guyatt GH, Keller JL, Jaeschke R, et al: The n-of-1 randomized control trial: Clinical usefulness. Our three-year experience. Ann Intern Med 112:293-299, 1990.
4. Guyatt G, Rennie D: Users’ Guides to the Medical Literature: A Manual for Evidence-Based Clinical Practice. Chicago, American Medical Association, 2002.
5. Larson EB, Ellsworth AJ, Oas J: Randomized clinical trials in single patients during a 2-year period. JAMA 270:2708-2712, 1993.
6. Levine M, Haslam D, Walter S, et al: Harm. In Guyatt GH, Rennie D (eds): Users’ Guides to the Medical Literature: A Manual for Evidence-Based Clinical Practice. Chicago, American Medical Association, 2002, pp 121-153.
7. Mahon J, Laupacis A, Donner A, Wood T: Randomised study of n of 1 trials versus standard practice. BMJ 312:1069-1074, 1996.
8. Millar AJ, Cywes S: Caustic strictures of the esophagus. In O’Neill JA, Rowe MI, Grosfeld JL, Coran AG (eds): Pediatric Surgery, 5th ed. St. Louis, Mosby, 1998, pp 969-979.
9. Sackett DL, Straus S, Richardson S, et al: Evidence-based Medicine: How to Practice and Teach EBM, 2nd ed. London, Churchill Livingstone, 2000.

Describe the pathophysiology of sinusitis.
Mucosal edema of the paranasal sinuses is the basic event leading to both acute and chronic disease. Edema may lead to obstruction of the drainage routes of the sinuses, causing stasis of secretions and an overall physiologic change in the sinus cavity. These local changes lead to impaired mucociliary clearance, alteration in local immune defenses, and ultimately bacterial overgrowth.
Perhaps the two most important potenital triggers underlying sinusitis are upper respiratory viral infection and upper airway allergy. Additional factors include environmental hypersensitivites, mucociliary dysfunction (primary and acquired), anatomic relationships (septal deviation, nasal polyposis), immunodeficiencies, and fungal hypersensitivities.

How do allergies predispose a patient to rhinosinusitis?
Type I atopy leads to the elaboration of multiple early- and late-phase inflammatory mediators. The result will be a multitude of mucosal changes in a sensitive patient. Mucus hypersecretion, edema, and impaired mucociliary function can occur, setting the stage for bacterial infection.

Which sinus is most often involved in rhinosinusitis?
In the majority of cases, the maxillary sinus and anterior ethmoid sinuses are involved. This can be predicted by the anatomy of the middle meatus or infundibulum, the location for drainage of the “anterior sinuses” (maxillary, anterior ethmoid, frontal sinuses)

Describe the signs and symptoms of acute bacterial rhinosinusitis (ABRS).
In can be very difficult to distinguish between ABRS and other causes of acute nasal congestion (viral rhinitis, allergic/nonallergic rhinitis). The 1996 Task Force on Rhinosinusitis developed a list of symptoms and signs to serve as a guideline in making the diagnosis of ABRS. A diagnosis of ABRS may be made in adults or children with a viral upper respiratory infection does not dissipate within 10 days (or worsens after 5-7 days) and is accompanied by some or all of these symptoms.
SIGNS AND SYMPTOMS OF ABRS
Nasal drainage
Nasal congestion
Facial pain/pressure (especially when unilateral and focused in the region of a particular sinus group)
Postnasal drip
Hyposmia/anosmia
Fever
Cough
Fatigue
Maxillary dental pain
Ear fullness/pressure

What are the most common organisms associated with ABRS?
Streptococcus pneumoniae (20-40%), Haemophilus influenzae (20-35%), and Moraxella catarrhalis (2-10%) are the most common pathogens associated with ABRS. Less common pathogens include Staphylococcus aureus (0-9%), anaerobes (0-9%), and streptococcal species (3-9%).
A relatively new issue in the management of ABRS is evolving antibiotic resistance. Essentially all of the most common pathogens in ABRS now demonstrate decreased antibiotic sensitivities to many of the commonly used drugs and related drug classes. This has directly affected antibiotic selection in the treatment of ABRS. The incidence of beta-lactamase production in isolates of H. influenzae is 30-40%, and for isolates of M. catarrhalis it is 92%.

Which organisms are associated with chronic bacterial rhinosinusitis (CRS)?
The same organisms found in acute disease are also prevalent in chronic rhinosinusitis. The following pathogens are more frequently associated with chronic rhinosinusitis: S. aureus, Pseudomonas aeruginosa, Proteus species, Enterobacter species, Klebsiella species, coagulase-negative Staphylococcus species, and possibly anaerobes. Generally speaking, gram-negative rods and staphylococcal species become more important pathogens in patients with CRS.

PREVALENCE OF ANTIMICROBIAL RESISTANCE AMONG ISOLATES OF S. PNEUMONIAE
Penicillin “nonsusceptible” 30%
Trimethoprim/sulfamethoxazole 37%
Macrolides 29%
Doxycycline 21%
Clindamycin 10%
Source: From Jacobs MR, Felmingham D, Appelbaum PC, Gruneberg RN, and the Alexander Project Group: The Alexander Project 1998-2000: Susceptibility of pathogens isolated from community-acquired respiratory tract infections to commonly used antimicrobial agents. J Antimicrob Chemother 52:229-246, 2003.

Describe the categories of fungal sinusitis.
Acute fulminant invasive fungal sinusitis is less than 4 weeks in duration and nearly universally involves patients who have some form of immunosuppression. The fungus is angioinvasive and destroys bone and tissue. It has a relatively high mortality and requires extensive surgical debridement of all nonviable tissue as well as systemic intravenous antifungal medication such as amphotericin B.
Chronic invasive fungal sinusitis is most commonly found in patients with diabetes mellitus, and Aspergillus fumigatus is the most common pathogen.
Granulomatous invasive fungal sinusitis has also been called indolent fungal sinusitis. It predominates in immunocompetent individuals, but it is invasive. The invasion is limited to the superficial mucosa. Granulomas surround the invasive fungal elements and limit deeper penetration. Fungus balls, or mycetomas, usually present as a unilateral opacification of either the maxillary or sphenoid sinus. Patients are classically immunocompetent without evidence of atopy.
Allergic fungal sinusitis is believed to be a type I, IgE-mediated hypersensitivity to fungal antigens present in the paranasal sinuses. Diagnostic criteria include fungal atopy, nasal polyposis, computed tomographic (CT) scan with evidence of hyperdense sinus infiltrate, allergic mucin with eosinophils, and fungal identification by culture or histopathology.
Eosinophilic fungal rhinosinusitis: Recent work at the Mayo Clinic has suggested a new or competing hypothesis for the etiology of chronic sinusitis, and in particular, the role of fungi. Though still controversial, their research proposes a T cell-mediated response to fungal antigens as the basic mechanism behind the chronic inflammatory state seen in many forms of chronic sinus disease.

What is Samter’s triad?
Samter’s triad is a syndrome with the following clinical features: (1) aspirin sensitivity (intolerance), (2) nasal polyposis, and (3) bronchospasm/asthma. When exposed to aspirin or nonsteroidal anti-inflammatory drugs, these patients will experience bronchospasm, worsening upper and lower airway inflammation, and often exacerbation of their sinus symptoms. Although not clearly understood, the pathophysiology appears to be at least in part due to dysfunction in the arachidonic acid metabolism pathway. These patients will typically have increased levels of the leukotrienes B4, C4, and D4 both in the serum and in the involved respiratory tissues. Approximately 10% of patients with nasal polyposis have aspirin intolerance.
KEY POINTS: PATHOPHYSIOLOGY, ETIOLOGY, AND CLASSIFICATION
The most common pathogens in both adult and pediatric ABRS are S. pneumoniae, H. influenzae, and M. catarrhalis.
The following antibiotic resistance patterns are important in ABRS: penicillin-resistant S. pneumoniae (25-40%), beta-lactamase-producing H. influenzae (30-40%), and beta-lactamase-producing M. catarrhalis (92%).
Eosinophilic infiltration is the hallmark of most forms of chronic hyperplastic rhinosinusitis; 50% of patients have asthma.
Samter’s triad includes aspirin sensitivity, asthma, and nasal polyposis.

What are the potential complications of sinusitis? Which complication is most common and why?
Complications include disease extension into the orbit or intracranial structures, facial cellulites, cavernous sinus thrombosis, osteomyelitis, visual changes, and mucocele formation. Orbital complications (preseptal or orbital cellulitis) are most common, owing to easy extension of infection along the thin sinus bone surrounding the orbit on three sides. Meningitis is usually regarded as the most common intracranial complication of sinusitis and can arise from the sphenoid or ethmoid sinuses. Although now rare owing to early treatment, epidural and subdural abscesses are associated with frontal sinusitis most commonly. A brain abscess may also occur in the setting of sinusitis (approximately 15% of cases) and carries a high mortality rate (20-30%). It is most often associated with frontal or ethmoid disease.

What are the treatment goals for ABRS?
The primary goals of this treatment are as follows: (1) to return the sinuses to a healthy state; (2) to decrease the duration of the patient’s symptoms; (3) to prevent complications associated with acute sinusitis; and (4) to prevent the development of chronic disease.

You have diagnosed the patient with ABRS. What is your management?
Studies in both adult and pediatric populations have confirmed that patients with ABRS treated with antibiotics will experience more rapid resolution of symptoms when compared with placebo. Although the spontaneous resolution rate for ABRS may approach 50%, the literature supports the use of antimicrobials in properly diagnosed patients.
In addition to antibiotics, the medical management of ABRS should include adjunctive treatments directed at reducing mucosal inflammation. These commonly include nasal steroids, topical decongestants (e.g., oxymetazoline, phenylephrine [Neo-Synephrine]), oral decongestants (e.g., pseudoephedrine), mucolytics (e.g., guaifenesin), and nasal saline irrigation.
The addition of topical corticosteroids to antibiotic therapy has recently been shown to improve patient symptoms within the first 7 days of treatment. Topical decongestants such as oxymetazoline or phenylephrine may be recommended for short-term use (2-5 days) as an adjunct to these therapies. These agents reduce mucosal and turbinate edema, allowing more effective drainage of the paranasal sinuses. In general, antihistamines are to be avoided in ABRS because anticholinergic adverse effects will thicken and dry secretions.

What are the antibiotics of choice in the treatment of pediatric ABRS?
A 10- to 14-day course is also recommended for children. Similar to the adult guidelines, the pediatric protocols are based on the current increased antibiotic resistance patterns encountered in clinical practice.
Agents for children with moderate disease or recent antibiotic use are amoxicillin/clavulanate and ceftriaxone. As in adults, failure of this group to elicit improvement should prompt reevaluation.

Discuss the role of anti-inflammatory agents in the treatment of CRS.
Whereas the importance of bacterial infection in CRS still remains debated, the importance of chronic inflammatory mucosal disease cannot be overemphasized. In many cases, attempts to control the inflammatory component of the disease are the cornerstone of therapeutic intervention. Important treatment options include prolonged intranasal steroids, the use of systemic steroids (oral, intramuscular), leukotriene receptor antagonists (e.g., montelukast, zafirlukast), and immunotherapy for allergic disease in select patients. The length and type of therapy will depend on clinical symptoms, stage of disease, and suspected underlying triggers. Patients with hyperplastic CRS will also have asthma in 50% of cases. These patients have been shown to have increased respiratory tissue eosinophilia with difficult-to-control mucosal inflammation.

Describe the role of antimicrobial treatment in CRS.
As outlined previously, the incidence of S. aureus, Staphylococcus epidermidis, P. aeruginosa, and other gram-negative organisms appear to be higher in CRS than in ABRS. This presents a problem in many cases due to reduced antibiotic sensitivities for these organisms. The end result may be a limited number of oral antibiotic options, potentially increasing the need for alternative delivery options (e.g., intravenous, topical). In cases where bacterial infection is suspected to be a major factor, the typical approach will be culture-directed antibiotic therapy for a minimum of 4 weeks. Duration of therapy will be dependent on patient symptoms, repeat culture data, nasal endoscopy, and CT findings.
KEY POINTS: MEDICAL MANAGEMENT OF ABRS

• The medical therapy for ABRS includes topical decongestants, topical corticosteroids, nasal saline irrigation, and antibiotics defined by specific guidelines.
• Medical management of ABRS involves agents that target the inflammatory process in addition to antibiotics.
• Complications of ABRS include facial cellulitis, orbital cellulitis, meningitis, cavernous sinus thrombosis, and intracranial abscess formation.

What role does fungus play in CRS?
The issue of fungal rhinosinusitis still remains controversial, although data suggest it is an important factor in some patients with CRS. If fungal CRS is suspected and confirmed, several options for treatment are available. Although oral antifungal protocols have been recommended (e.g., itraconazole daily for 3-6 months), their efficacy has not been established. Antifungal sinus irrigations have been used in some form for decades. Recently, the Mayo Clinic group began using amphotericin B (100 µg/mL) 20 mL per nostril per day as a topical treatment method. Preliminary data have been encouraging, but prospective controlled data are pending.

Surgical Management

What is the role of surgical intervention in rhinosinusitis?
Surgery is a key component in the comprehensive management of rhinosinusitis. For complicated acute sinusitis, such as subperiosteal or epidural abscesses, the role of surgery is acute decompression of the affected sinuses as well as the area of abscess. For chronic or recurrent sinusitis, the role of surgery is to facilitate the natural drainage of the sinuses, when possible, through correction of identifiable anatomic aberrations. Generally speaking, surgery is not a cure for CRS but an adjunctive treatment option for select patients. Medical management remains the primary option for rhinosinusitis and is effective in the majority of patients.

What surgical procedures are commonly performed for nasal obstruction?
Septoplasty is the correction of a deviation in the nasal septum responsible for obstruction of the nasal airway. This deviation may involve the cartilaginous or bony segments of the nasal septum and commonly involves both. This procedure may also be necessary during endoscopic sinus surgery to provide access to the middle meatus.
Inferior turbinate hypertrophy also frequently contributes to nasal obstruction. Reduction of the inferior turbinates may be performed by many methods, including excision, electrocautery, radiofrequency ablation, and submucous resection/reduction. The function of the inferior turbinates is complex and invaluable; thus radical resection or surgical maneuvers that potentially disrupt function should be avoided.

What is functional endoscopic sinus surgery (FESS)?
Endoscopic sinus surgery has become the preferred technique for the surgical management of most forms of rhinosinusitis. FESS describes a series of techniques that use nasal endoscopes for access to the paranasal sinuses rather than external approaches. The concept of functional surgery implies using techniques that facilitate the natural drainage patterns of the sinuses through the osteomeatal complex, rather than creating alternative drainage pathways that are contrary to physiologic mucociliary flow. The key concept is atraumatic surgical technique, mucosal preservation, and restoration of normal sinus physiology.

Describe the preoperative evaluation of patients undergoing FESS.
An accurate history including previous medical therapy is vital to identify candidates likely to benefit from surgery. Complete head and neck physical examination including nasal endoscopy will allow the nasal anatomy and mucosa to be evaluated. Coronal sinus CT scans are an important component of this evaluation. These are vital for evaluating the sinus anatomy and for identifying the presence of mucosal disease. Several CT staging systems exist for grading the extent of rhinosinusitis. Overall, FESS may be considered an option in patients with persistent symptoms of rhinosinusitis combined with objective evidence of disease on endoscopy and/or CT despite maximal medical therapy.

What are the basic principles of FESS surgery?
As emphasized previously, the goal of FESS is to minimize mucosal trauma to the paranasal sinuses while providing drainage for the sinuses. Thus, resection of diseased mucosa and anatomic structures must be minimized to optimize functional outcome. Osteomeatal complex obstruction or infundibular disease may first be addressed by the performance of a maxillary antrostomy. The maxillary sinus ostium is exposed by removing the uncinate process. If indicated, the maxillary ostium may be enlarged using a variety of instruments. Then, as indicated, an anterior ethmoidectomy may be performed by first opening the ethmoid bulla. Dissection proceeds posteriorly along the inferomedial aspect of the ethmoid labyrinth until the basal lamella of the middle turbinate is encountered, marking the demarcation between the anterior and posterior ethmoid cells. The dissection then proceeds superiorly along the lamella to the skull base. Remaining ethmoid cells are dissected with the skull base superiorly and lamina papyracea laterally serving as limits of dissection. Superiorly, the frontal recess is identified. If frontal disease is present, the outflow tract may be cleared of cells and mucosal disease allowing for ventilation of the frontal sinus. As indicated, the posterior ethmoids may be dissected by continuing the anterior dissection posteriorly through the basal lamella. If necessary, a sphenoidotomy can be performed by first identifying the natural ostium of the sphenoid sinus followed by enlarging the os (natural sphenoid opening) inferiorly and medially. The sphenoid os is located medially to the superior turbinate 80% of the time. The sphenoid os may be approached via a transnasal or transethmoidal route.
KEY POINTS: SURGICAL MANAGEMENT OF ABRS

1. FESS has replaced external approaches as the standard surgical management of rhinosinusitis.
2. The key concepts of FESS involve atraumatic surgical technique, mucosal preservation, and restoration of normal sinus physiology.
3. Coronal sinus CT scans are essential studies to obtain before FESS to define pathology and minimize surgical complications (e.g., presence of low-lying cribriform plate).
4. The major complications of FESS include orbital injury, intracranial injury, and cerebrospinal fluid leak. Prompt recognition and resolution of these conditions are imperative.

Discuss the surgical approaches to the frontal sinus.
Advanced endoscopic techniques have allowed for better visualization and improved management of frontal sinus disease. Although often requiring special instrumentation and extensive experience, endoscopic frontal sinusotomy has become the preferred approach in many cases. Angled forceps, curved suction devices, and the 45-degree endoscope are just a few of the technologic advances that have made endoscopic frontal sinus surgery possible. Computer-aided sinus surgery or image-guided sinus surgery has also added to our ability to safely and effectively approach the frontal sinus endoscopically. The frontal sinus may also be approached externally via a Lynch incision superior to the medial canthus and inferior to the medial aspect of the eyebrow. Additional external approaches include a bicoronal flap for direct access to the anterior table of the frontal sinus, with an osteoplastic flap developed to enter the sinus. This approach is most commonly used for frontal sinus cranialization, for frontal sinus obliteration procedures, or for access to anterior skull base lesions.

What are the complications of FESS?
The major complications of FESS involve orbital and intracranial injury. Orbital injury ranges from periorbital ecchymosis and emphysema to orbital hematoma and blindness. Prompt recognition of developing orbital complications is paramount to preventing further and permanent damage to the eye. Anisocoria, ophthalmoplegia, and proptosis are ominous signs demanding prompt action. Measures to relieve orbital pressure include the administration of steroids or mannitol or the performance of orbital decompression via lateral canthotomy, external ethmoidectomy, or endoscopic orbital decompression.
Intracranial complications of FESS include CSF leak, meningitis, direct brain injury, carotid artery injury, and tension pneumocephalus. The most likely sites of skull base breach include the cribriform plate and roof of the ethmoid sinus. If identified intraoperatively, successful endoscopic repair is likely (> 90% success).
Other complications of FESS include lacrimal injury, anosmia, major hemorrhage from the ethmoid or sphenopalatine arteries, synechiae, and mucociliary dysfunction secondary to overresection of anatomic structures.

Last Updated: 03/10/2010

References:

1. Benninger MS, Ferguson BJ, Hadley JA, et al: Adult chronic rhinosinusitis: Definitions, diagnosis, epidemiology, and pathophysiology. Otol Head Neck Surg 129:S1-S32, 2003.
2. Jacobs MR, Felmingham D, Appelbaum PC, et al: The Alexander Project 1998-2000: Susceptibility of pathogens isolated from community-acquired respiratory tract infections to commonly used antimicrobial agents. J Antimicrob Chemother 52:229-246, 2003.
3. Kennedy DW, Bolger WE, Zinreich SJ: Diseases of the Sinuses: Diagnosis and Management. Hamilton, Ontario, B.C. Decker Inc., 2001.
4. Lanza DC, Kennedy DW: Adult rhinosinusitis defined. Otolaryngol Head Neck Surg 117:S1-S7, 1997.
5. Lund VJ, Kennedy DW: Staging for rhinosinusitis. Otolaryngol Head Neck Surg 117:S35-S40, 1997.
6. Senior BA, Kennedy DW, Tanabodee J, et al: Long-term results of functional endoscopic sinus surgery. Laryngoscope 108:151-157, 1998.
7. Sinus and Allergy Health Partnership: Antimicrobial treatment guidelines for acute bacterial rhinosinusitis. Otolaryngol Head Neck Surg 130(Suppl 1): 1-45, 2004.
8. Stankiewicz JA: Complications of endoscopic sinus surgery. Otolaryngol Clin North Am 22:749-758. 1989.
9. Williams JW Jr, Aguilar C, Cornell J, Chiquette ED, et al: Antibiotics for acute maxillary sinusitis [update of Cochrane Database Syst Rev 2000;(2):CD000243; PMID: 10796515]. Cochrane Database of Systematic Reviews. (2):CD000243, 2003.

What pathophysiology underlies rhinitis?
Nasal congestion arises from engorgement of blood vessels due to the effects of vasoactive mediators and neural stimuli. Rhinorrhea is due to hypersecretion of the nasal glands, leading to tissue transudate. The autonomic nervous system mediates both vascular tone and secretions. Sympathetic innervation constricts the vessels, decreasing congestion, whereas the parasympathetic innervation vasodilates the vessels, enhancing congestion. Itching occurs in association with histamine release from mast cells and basophils secondary to antigenic stimulation.

Is there a link between rhinitis and asthma?
Yes. It is becoming more and more clear that the upper airway and lower airway are linked, and the term “the united airways” has been coined by some. The similarities are that they are both lined by columnar epithelium and the airway epithelium is at the center of pathogenesis in both rhinitis and asthma. Rhinitis is a strong independent risk factor for asthma (perennial greater than allergic) and up to 40% of allergic rhinitis patients have asthma. Also, the severity of a patient’s allergic rhinitis has been shown to correlate with the asthma severity. However, the comparison of upper and lower airway is not absolute. Pathophysiologically, the lower airway exhibits more epithelium shedding than the upper airway, and eosinophilia is more predominant in the lower airway of persons with asthma.

How is rhinitis categorized?
Rhinitis can be divided into allergic and nonallergic types.

Allergic Rhinitis

Describe the allergic response in allergic rhinitis.
The primary phase involves a type 1 Gell and Coombs type of hypersensitivity with the antigen binding to immunoglobulin (Ig) E receptors, causing mast cells and basophils to release mediators such as histamine, serotonin, leukotrienes, and prostaglandins. This phase occurs within 5 minutes of antigen exposure. The late phase (secondary phase) occurs 4-6 hours after antigen exposure and involves the migration of inflammatory cells (neutrophils and eosinophils) and the release of mediators by basophils.

What are the “allergic salute,” “allergic shiners,” and “allergic gape”?
Patients (particularly children) with persistent rhinorrhea often wipe the nose in a upward direction with the palm of the hand, which has been referred to as the allergic salute. Consequently, these patients may have a horizontal crease in the skin of the lower nose by the tip. Also, patients with allergic rhinitis can have darkened areas under their eyes, which are referred to as allergic shiners. The allergic gape is a characteristic open mouth from nasal obstruction causing mouth breathing.

What complications are associated with allergic rhinitis?
Poorly controlled symptoms of allergic rhinitis can lead to a surprising amount of disability, with reported 3.5 million work days lost and 2 million school days missed. Consequences include sleep loss with daytime somnolence, significant cognitive disability, and reduced quality of life. Children in particular can suffer psychosocial detriment and learning difficulties. Quality of life is affected more by rhinitis than by asthma. Subsequent pathologies can evolve, including sinusitis, otitis media with hearing loss, abnormal craniofacial abnormalities, and/or aggravation of asthma. Some treatments for allergic rhinitis may also indirectly contribute to lack of productivity, such as first-generation H1 antihistamines that, unfortunately, are sedating.

How do antihistamines aid in the treatment of allergic rhinitis?
Antihistamines act by blocking H1-receptor sites, thereby interfering with mast cell and basophil histamine release. Although the first-generation antihistamines are associated with drowsiness, the newer ones are nonsedating and, where applicable, should be preferred over the first-generation drugs. Interestingly, the newer antihistames have also been found to exhibit a degree of anti-inflammatory effect. They can be used orally or intranasaly and reduce rhinorrhea, itching, and sneezing, as well as some blockage. Nasal antihistamines have a significantly faster onset of action than oral antihistamines.

How do steroids aid in treating allergic rhinitis?
Topical steroids decrease local inflammation caused by vasoactive mediators, decrease rhinorrhea by reducing the reactivity of acetylcholine receptors, decrease basophil and eosinophil counts, and decrease sneezing by desensitizing irritant receptors. Because of a slow onset of action, it can take days or a week to obtain maximum benefits.

What role does ipratropium bromide play in the treatment of allergic rhinitis?
Ipratropium bromide is a topical anticholinergic agent that antagonizes the effect of acetylcholine at parasympathetically innervated submucosal glands. It is effective in reducing the mucosal gland hypersecretion that causes rhinorrhea, but it is ineffective against the other symptoms of congestion, itching, and sneezing. Combining ipratropium with nasal steroids produces a greater effect on rhinorrhea than either alone. Its use may be beneficial in a select group of patients in whom rhinorrhea predominates over other symptoms.

How may immunotherapy benefit patients with allergic rhinitis?
Immunotherapy can be effective in patients who are sensitive to allergens for which a potent extract is available and who have severe symptoms that fail medical management. Age and comorbidity limit patient suitability and there can be serious adverse effects, including anaphylaxis. The treatment involves injecting the offending antigen into the patient. Improvement can require many months and, if it occurs, therapy should continue for 3-5 years. Although there are many proposed mechanisms, the overall mechanism behind the relief of immunotherapy is unknown.

Non Allergic Rhinitis

List the causes of nonallergic rhinitis.

• Pharmacology (rhinitis medicamentosa)
• Infection
• Structural abnormalities
• Irritatation
• Hormonal factors
• Atrophy
• Substance abuse (e.g., cocaine, alcohol, nicotine)
• Foreign bodies
• Trauma
• Temperature
• Exercise
• Recumbency
• Emotions
• Decreased nasal airflow states (e.g., after laryngectomy or tracheostomy)
• Systemic diseases (e.g., Wegener’s granulomatosis, sarcoid, superior vena cava syndrome, and Horner’s syndrome)
• Idiopathic disease (e.g., vasomotor rhinitis, eosinophilic or basophilic nonallergic rhinitis)

What is rhinitis medicamentosa?
Rhinitis medicamentosa is drug-induced rhinitis that is caused by rebound nasal congestion. It is often associated with prolonged use of topical decongestants. It is thought that a semi-ischemic state is induced by the strong vasoconstrictive effect of topical decongestants. With time, this effect leads to the metabolic accumulation of vasodilators that are responsible for the rebound vasodilation. The condition can become irreversible with the development of vascular atony. Also, benzalkonium chloride, a preservative in some vasoconstrictor preparations, can cause mucosal irritation and decreased mucoilliary clearance via ciliostasis and can exasperate rhinitis medicamentosa.

How is rhinitis medicamentosa treated?
The administration of topical decongestants should be discontinued. Systemic decongestants (if appropriate) and nasal saline spray can provide symptomatic relief. Also, the administration of topical steroids can be started to decrease congestion and the withdrawal effect. It is paramount that the patient is educated on “abuse” of topical decongestants and that he or she understands that the topical steroids will not give the normal fast response of the decongestant and that days may be required for a maximal effect to occur. Without this information, the patient could revert to his old habits, dissapointed with the steroid effect. Furthermore, the initial cause of obstruction that led to the use of topical decongestants should be specifically treated (e.g., allergy, structural problem, infection).

Name some structural abnormalities that can cause rhinitis.

• Deviated nasal septum
• Turbinate hypertrophy
• Nasal valve collapse
• Polyps
• Neoplasms (e.g., papilloma, angiofibroma, malignancy)
• Intranasal and extranasal deformities

What is occupational rhinitis? How does the effect of irritants in nonallergic rhinitis differ from an allergic response?
Occupational rhinitis is divided into two types: (1) irritants that cause rhinitis and (2) allergic rhinitis. Dust, gases (e.g., formaldehyde), chemicals, and air pollution (e.g., smoke, sulfur dioxide) can cause nasal congestion and rhinorrhea via direct irritative effects on the mucosa. In contrast, an allergic response is due to interaction with IgE antibodies and histamine-releasing cells. Accordingly, the history for irritant rhinitis involves transient symptoms when exposed to the irritant, and as toxic damage to the mucosa occurs, the symptoms may not abate with short rest periods or on cessation of work. With allergic rhinitis, the symptoms generally improve with short rest periods and disappear after exposure to the allergen.

Describe the endocrine or hormonal causes of nonallergic rhinitis.
Pregnancy, menstruation, and oral contraceptive use can all cause nasal congestion. The increased estrogen levels associated with these states inhibit acetylcholinesterase, leading to increased parasympathetic tone and tissue edema. Hypothyroidism is also associated with rhinitis. In this state, parasympathetic activity predominates over the hypoactive sympathetic state, causing vasodilation of the nasal mucosa.

What is atrophic rhinitis?
Atrophic rhinitis, or ozena, is associated with atrophy of the nasal mucosa and turbinates in association with excessive crusting and mucopurulent discharge. This socially debilitating condition is marked by an extremely foul odor that can be easily detected by others. Patients often complain of epistaxis, nasal obstruction, headaches, and the foul smell. Although the cause is unknown, hereditary, infectious, developmental, nutritional, and endocrine factors have been implicated. Atrophic rhinitis may also be iatrogenic because it may be associated with excessive turbinate resection. Although no cure exists, treatment revolves around frequent saline irrigation and topical antibiotics. Surgical options have been aimed at narrowing the nasal cavity and nostril.

Date Last Updated: 03/08/2010
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