Treatment of laryngopharyngeal reflux.

Abstract

Proton-pump inhibitors form the cornerstone of antireflux therapy for laryngopharyngeal reflux. In this article, we provide algorithms to guide the management of minor, major, and life-threatening cases.

Introduction

The treatment of laryngopharyngeal reflux (LPR) has changed over time, often following the development of new medications. Initial treatment regimens involved antacids and dietary and lifestyle changes, but they were only minimally effective. With the introduction of the 2 receptor antagonists, only about 50% of LPR patients responded to treatment, leaving a significant proportion of patients without benefit. (1-4) In the late 1980s, protonpump inhibitors (PPIs) were introduced in the United States. These drugs directly target [H.sup.+]-[K.sup.+] ATPase, the key enzyme in the final acid production pathway within the parietal cell. The elimination or marked suppression of acid production by PPIs accomplished two things: It reduced exposure of damaged tissues to an acidic environment and, more important, it reduced the activity of pepsin, which requires an acidic pH level for activation. (Pepsin retains 70% of its activity at a pH level of 4.5. (5,6)

Clinical trials confirmed the superiority of PPIs to 112 receptor antagonists. In LPR, acid must be suppressed around the clock because the larynx is more susceptible to injury from refluxate than is the esophagus. (7,8) However, PPIs are not effective in all LPR patients, especially with once-daily dosing. Studies of once-a-day dosing have demonstrated significant failure rates. (9,10) Other studies have shown that the average morning dose of a PPI lasts an average of only 13.8 hours (11) and that the evening close lasts just 7.5 hours. (12) There have been reports of LPR treatment failures, even on high-dose PPI therapy. (10,13) We found a medical treatment failure rate of 10% in LPR patients who received a PPI as many as four times per day. (10)

Unlike symptoms of gastroesophageal reflux disease, LPR symptoms do not resolve quickly, often taking several months to resolve. (7,14) One study revealed that fewer than half of patients treated with PPIs were completely well after 4 months of therapy. (15) Despite the fact that they are not completely effective in all patients, PPIs are still considered the standard therapy for patients with moderate to severe findings or complications of LPR. (14)

Antireflux therapy has two simultaneous goals: (1) to arrest the inflammatory process in the larynx by inhibiting gastric acid and (2) to reconstitute the body's normal antireflux defenses, if possible. An initial 6-month period of medical therapy should be attempted to optimize reversible risk factors that are within the patient's control. For example, some patients report that LPR seems to decrease significantly with weight loss, dietary changes, or smoking cessation.

We classify LPR into one of three groups--minor, major, and life-threatening--based on the patient's symptoms, findings, and occupation. Patients with minor reflux consider their symptoms to be annoying, but they do not impair their ability to perform their job or to interact socially. Major reflux occurs when symptoms begin to have a significant impact on work or social life. Mild intermittent hoarseness in most patients might not be significant, but the same symptom in an opera singer might be catastrophic. Life-threatening reflux occurs when patients experience airway obstruction, including glottic or subglottic stenosis (figure), webs, laryngospasm, severe paradoxical vocal fold movement, asthma, dysplasia, and laryngeal carcinoma.

Minor LPR

In many otolaryngology practices, most LPR patients have the minor form. These patients typically experience symptoms of intermittent dysphonia, chronic throat clearing, globus pharyngeus, and dysphagia, and they frequently exhibit findings such as laryngeal edema and posterior laryngitis.

The initial treatment of minor reflux varies, but it is appropriate to adopt a less aggressive approach to management. We often recommend routine dietary and lifestyle modifications (e.g., smoking cessation and a reduction of alcohol intake) when certain behaviors put the patient at risk for reflux. (16) Other first-line management options include an [H.sub.2] receptor antagonist or an antacid. In general, we do not recommend elevation of the head of the bed unless the patient demonstrates supine nocturnal reflux by pH monitoring.

When a conservative regimen works, it is cost-effective. If it should fail, the patient should be prescribed a PPI, starting at a twice-daily dose. The dose can be increased to achieve a therapeutic response. Adequate time must be given for healing to occur.

Any patient who appears to be failing high-dose PPI therapy should undergo pH monitoring while on medication to evaluate drug efficacy. If the therapy fails in this study, the clinician can either change the dose or type of PPI or, in more severe cases, refer the patient for possible fundoplication. (17)

Regardless of the level of medical therapy, treatment should be continued for a minimum of 6 months. If the patient becomes asymptomatic after this time, the medication can be decreased or discontinued. However, it is important to counsel patients prior to decreasing or terminating treatment that LPR might relapse. Many patients have disease-free intervals of months or years only to eventually experience a recurrence. Some LPR patients need continual lifetime treatment.

The chronic-intermittent pattern of LPR requires the clinician to individualize treatment. Some LPR patients who are relatively asymptomatic, especially professional vocalists, need close, long-term follow-up to prevent the recurrence of significant symptoms.

Major LPR

Most of the patients we see at our voice center fall into the major and life-threatening categories. For patients with major LPR, we recommend beginning with dietary and lifestyle modification plus a twice-daily PPI. We recommend that the first PPI dose be taken in the morning before breakfast and the second in the afternoon prior to the evening meal. The absorption of PPIs varies, but virtually all of them are best absorbed when taken well before meals.

We generally see patients at 2-month intervals. We track their treatment progress with the assistance of the reflux symptom index (RSI) and the reflux finding score (RFS). After 2 months of treatment, many patients have achieved significant symptomatic improvement, even though there is a lesser degree of improvement of the laryngeal findings. (18) It is rare for a larynx to look normal after 2 months of antireflux treatment. If the patient is no better at the 2-month visit, we sometimes double the PPI dosage. Depending on the reflux pattern demonstrated on pH monitoring, an [H.sub.2] receptor antagonist might be given before bed to limit nocturnal acid breakthrough. If the treatment still appears to be failing at the 4-month visit, pH monitoring is undertaken to evaluate drug efficacy. In many cases, the PPI is changed from one brand to another; some patients are referred for laparoscopic fundoplication.

After a patient has had two consecutive normal laryngeal examinations (RFS <5) and is essentially asymptomatic (RSI <10), we begin tapering the PPI dose before weaning the patient off medication. We believe that tapering is necessary because there appears to be a rebound phenomenon following the acute cessation of PPI therapy. At first, the evening dose of the PPI is stopped and an [H.sub.2] receptor antagonist, usually ranitidine, is taken in its place. Two weeks later, the morning PPI dose is likewise switched to ranitidine. Repeat examinations are conducted at 2 and 4 months. If patients remain asymptomatic after 4 months, we usually allow them to taper themselves off the [H.sub.2] blocker. But if a patient experiences recurrent symptoms or findings, the PPI dosage is again escalated in a stepwise fashion over a period of weeks or months. If medical treatment appears to be failing despite a significant dose of an [H.sub.2] receptor antagonist, the patient might need to resume PPI therapy.

Life-threatening LPR

Life-threatening LPR requires aggressive reflux control. We usually start the patient on a three- or four-times-daily PPI regimen. In addition, we strongly recommend pH testing with full manometry to obtain a baseline evaluation and later to monitor response after the initiation of treatment. Moreover, we often recommend fundoplication for these patients.

Ideally, all patients with laryngeal carcinoma, stenosis, and laryngospasm should undergo pH monitoring before treatment is initiated. Certainly, this is not always possible, particularly when patients require emergency surgery. Nevertheless, every effort should be made to obtain pH monitoring prior to treatment, because (1) it establishes the diagnosis of LPR, (2) it determines the severity of LPR (and establishes a baseline), (3) it allows treatment to be individualized, and (4) the results might justify early fundoplication. In fact, fundoplication should be considered as an early alternative in selected cases--for example, in patients with severe LPR, particularly young patients (<40 yr). (17) Fundoplication might be the optimal treatment for a young patient with subglottic stenosis who has no history of trauma or intubation and who has a Low LES pressure and pH-metry evidence of severe LPR.

In patients with life-threatening LPR older than 60 years, long-term twice-daily PPI treatment is recommended. On the other hand, if such a patient has only supine or upright reflux disease, a single daily dose might suffice as maintenance therapy after the acute phase of the illness has resolved. However, considerable variability is seen in these patients, and treatment must be individualized.

For patients younger than 40 years who require long-term therapy, fundoplication should be considered. For patients between the ages of 40 and 60 years, treatment is selected on an individual basis depending on the severity of the LPR, the symptoms of the underlying condition, the patient's preferences, and the patient's overall medical condition.

Fundoplication as a surgical antireflux treatment is highly effective. However, it does appear to require significant experience and expertise on the part of the surgeon. Laparoscopic fundoplication has been shown to be highly successful, and it eliminates much of the morbidity associated with the traditional approach. (17)

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