Gastroesophageal Reflux Disease Treatment & Management

Treatment of gastroesophageal reflux disease (GERD) involves a stepwise approach. The goals are to control symptoms, to heal esophagitis, and to prevent recurrent esophagitis or other complications. The treatment is based on (1) lifestyle modification and (2) control of gastric acid secretion through medical therapy with antacids or PPIs or surgical treatment with corrective antireflux surgery. ^{[1, 2, 3, 4, 5, 6]}

Approximately 80% of patients have a recurrent but nonprogressive form of GERD that is controlled with medications. (See Pharmacologic Therapy.) Identifying the 20% of patients who have a progressive form of the disease is important, because they may develop severe complications, such as strictures or Barrett esophagus. For patients who develop complications, surgical treatment should be considered at an earlier stage to avoid the sequelae of the disease that can have serious consequences. (See Surgical Care.)

Use of a patient management tool such as the self-administered GERD Questionnaire (GerdQ) to stratify patients may improve the management of GERD patients in primary care settings. ^[28]

Lifestyle modifications include the following:

• Losing weight (if overweight)

• Avoiding alcohol, chocolate, citrus juice, and tomato-based products (2005 guidelines from the American College of Gastroenterology [ACG] also suggest avoiding peppermint, coffee, and possibly the onion family ^[7] )

• Avoiding large meals

• Waiting 3 hours after a meal before lying down

• Elevating the head of the bed by 8 inches

According to the ACG 2005 guidelines, studies have shown decreased distal esophageal acid exposure after these changes are made, but few data are available to confirm these findings. ^[7]

Lifestyle modifications are the first line of management in pregnant women with GERD. Advise patients to elevate the head of the bed; avoid bending or stooping positions; eat small, frequent meals; and refrain from ingesting food (except liquids) within 3 hours of bedtime.

Antacids

Antacids were the standard treatment in the 1970s and are still effective in controlling mild symptoms of GERD. Antacids should be taken after each meal and at bedtime.

H2 receptor antagonists and H2 blocker therapy

H2 receptor antagonists are the first-line agents for patients with mild to moderate symptoms and grades I-II esophagitis. Options include cimetidine (Tagamet), famotidine (Pepcid), and nizatidine (Axid). The US Food and Drug Administration announced voluntary recalls of ranitidine (Zantac) from the market between December 2019 and February 2020 after raising major concerns in September 2019 about drug contamination with the impurities of the carcinogenic molecule N-nitrosodimethylamine (NDMA). ^[29] A total withdrawal of all ranitidine products was requested in April 2020. ^[30]

H2 receptor antagonists are effective for healing only mild esophagitis in 70%-80% of patients with GERD and for providing maintenance therapy to prevent relapse. Tachyphylaxis has been observed, suggesting that pharmacologic tolerance can reduce the long-term efficacy of these drugs.

Additional H2 blocker therapy has been reported to be useful in patients with severe disease (particularly those with Barrett esophagus) who have nocturnal acid breakthrough.

Proton pump inhibitors

PPIs are the most powerful medications available for treating GERD. These agents should be used only when this condition has been objectively documented. They have few adverse effects. However, data have shown that PPIs can interfere with calcium homeostasis and aggravate cardiac conduction defects. Long-term use of these agents has also been associated with bone fractures in postmenopausal women, chronic renal disease, acute renal disease, community-acquired pneumonia, and Clostridium difficile intestinal infection. ^{[31, 32]}

Available PPIs include omeprazole (Prilosec), lansoprazole (Prevacid), rabeprazole (Aciphex), and esomeprazole (Nexium). In November 2013, the FDA approved the first generic versions of rabeprazole sodium delayed-release tablets for the treatment of GERD in adults and adolescents ages 12 and up. In clinical trials, the most commonly reported adverse reactions to rabeprazole were sore throat, flatulence, infection, and constipation in adults, and abdominal pain, diarrhea, and headache in adolescents. ^[33]

A research review by the Agency for Healthcare Research and Quality (AHRQ) concluded, on the basis of grade A evidence, that PPIs were superior to H2 receptor antagonists for the resolution of GERD symptoms at 4 weeks and healing of esophagitis at 8 weeks. ^[34] In addition, the AHRQ found no difference between individual PPIs (omeprazole, lansoprazole, pantoprazole, and rabeprazole) for relief of symptoms at 8 weeks. For symptom relief at 4 weeks, esomeprazole 20 mg was equivalent, but esomeprazole 40 mg superior, to omeprazole 20 mg. ^[34]

A systematic review and meta-analysis of two randomized trials and four prospective cohort studies on the effects of PPI in obstructive sleep apnea in patients with GERD found a lack of definitive data. ^[35]

Prokinetic medications and reflux inhibitors

Prokinetic agents are somewhat effective but only in patients with mild symptoms; other patients usually require additional acid-suppressing medications, such as PPIs. The usual regimen in adults is metoclopramide, 10 mg/day orally. Long-term use of prokinetic agents may have serious, even potentially fatal, complications and should be discouraged.

As in many other fields, surgical therapy for gastroesophageal reflux has evolved a great deal. A few historical procedures of note include the Allison crural repair, the Boerema anterior gastropexy, and the Angelchik prosthesis. Both the Allison and the Boerema repairs have high failure rates and are rarely, if ever, used. ^{[36, 37]} The Angelchik prosthesis is a silicone ring that is positioned at the gastroesophageal junction and prevents reflux. The Angelchik prosthesis was rarely used in children and has been largely abandoned because of a high rate of complications. ^[38]

Today, both transthoracic and transabdominal fundoplications are performed, including partial (anterior or posterior) and circumferential wraps. The most commonly performed operation today in both children and adults is the Nissen fundoplication, which is a 360° transabdominal fundoplication (see the image below). ^{[39, 40]} First reported in 1991, laparoscopic fundoplication is well studied in adult populations. Laparoscopic fundoplication has also quickly gained acceptance for use in children. ^{[41, 42, 43, 44, 45, 46]} However, in one study in which 119 children underwent fundoplication for severe GERD, 7.6% required a redo fundoplication and 53.8% needed to restart their antireflux medications within 6 months of surgery. ^[47]

Indications for fundoplication include the following:

• Patients with symptoms that are not completely controlled by PPI therapy can be considered for surgery; surgery can also be considered in patients with well-controlled GERD who desire definitive, one-time treatment

• The presence of Barrett esophagus is an indication for surgery (whether acid suppression improves the outcome or prevents the progression of Barrett esophagus remains unknown, but most authorities recommend complete acid suppression in patients with histologically proven Barrett esophagus)

• The presence of extraesophageal manifestations of GERD may indicate the need for surgery; these include the following: (1) respiratory manifestations (eg, cough, wheezing, aspiration); (2) ear, nose, and throat manifestations (eg, hoarseness, sore throat, otitis media); and (3) dental manifestations (eg, enamel erosion)

• Young patients

• Poor patient compliance with regard to medications

• Postmenopausal women with osteoporosis

• Patients with cardiac conduction defects

• Cost of medical therapy

Several randomized clinical trials have challenged the benefits of surgery in controlling GERD. Lundell followed up his cohort of patients for 5 years and did not find surgery to be superior to PPI therapy. ^[48] Spechler found that, at 10 years after surgery, 62% of patients were back on antireflux medications. ^[49] A very rigorous, randomized study by Anvari et al reestablished surgery as the criterion standard in treating GERD. ^[50] The investigators showed that, at 1 year, the outcome and the symptom control in the surgical group was better than that in the medical group. ^[50]

A British multicenter randomized study conducted by Grant et al also compared surgical treatment versus medical therapy in patients with documented evidence of GERD. ^[51] The type of laparoscopic fundoplication was decided by the respective surgeons. Individuals who had received medication for their condition had taken them for a median of 32 months before participating in the study. The investigators reported that by 12 months, 38% of those who had undergone surgery were taking reflux medication, compared with 90% of the individuals randomized to medical management. ^[51]

Long-term results of laparoscopic antireflux surgery have shown that, at 10 years, 90% of patients are symptom free and only a minority still take PPIs. ^[52]

Long-term follow-up results from a multicenter, randomized trial showed that, relative to pharmacotherapy, fundoplication maintained better symptomatic relief in the management of gastroesophageal reflux disease without evidence of long-term postsurgical adverse symptoms. At 5 years, among patients with a treatment response, almost twice as many of those randomized to medical management (82%) were taking antireflux agents relative to those who had been randomized to surgery (44%). ^[53]

Laparoscopic fundoplication

Laparoscopic fundoplication is performed under general endotracheal anesthesia. Five small (5-mm to 10-mm) incisions are used (see image below). The fundus of the stomach is wrapped around the esophagus to create a new valve at the level of the esophagogastric junction.

The essential elements of the operation are as follows:

• Complete mobilization of the fundus of the stomach with division of the short gastric vessels

• Reduction of the hiatal hernia

• Narrowing of the esophageal hiatus

• Creation of a 360° fundoplication over a large intraesophageal dilator (Nissen fundoplication)

Laparoscopic fundoplication procedure takes about 2-2.5 hours. The hospital stay is approximately 2 days. Patients resume regular activities within 2-3 weeks. Approximately 92% of patients obtain resolution of symptoms after undergoing laparoscopic fundoplication.

The AHRQ found, on the basis of limited evidence, that laparoscopic fundoplication was as effective as open fundoplication in relieving heartburn and regurgitation, improving quality of life, and decreasing the use of antisecretory medications. ^[34]

Although a prospective, randomized trial has never been performed to compare PPIs to laparoscopic fundoplication, the authors believe fundoplication is preferable for the following reasons:

• PPIs, although effective in controlling the acid component of the refluxate, do not eliminate the reflux of bile, which some believe to be a major contributor to the pathogenesis of Barrett epithelium

• Patients with Barrett esophagus tend to have lower LES pressure and worse esophageal peristalsis than patients without Barrett esophagus; patients with Barrett esophagus are also exposed to a larger amount of reflux

• A fundoplication offers the only possibility of stopping any kind of reflux by creating a competent LES; however, until the definitive answer is known, the authors recommend that patients with Barrett esophagus should continue to undergo periodic endoscopic surveillance even after laparoscopic fundoplication

Sleeve gastrectomy

In a study that evaluated laparoscopic sleeve gastrectomy for GERD in 71 morbidly obese patients, symptomatic and reflux control improved in most patients following the procedure. ^[54] However, a systematic review and meta-analysis of 33 studies was unable to determine the effect of sleeve gastrectomy on the prevalence of GERD owing to the high heterogeneity among the available studies and paradoxical outcomes of objective esophageal function tests. ^[55]

Devices

The US Food and Drug Administration approved the LINX Reflux Management System in March 2012. This device is designed to augment the lower esophageal sphincter. The system is a small flexible band that is placed laparoscopically around the esophagus just above the stomach to create a natural barrier to reflux. The band consists of interlinked titanium beads with magnetic cores. The act of swallowing temporarily breaks the magnetic bond, allowing food and liquid to pass normally. ^[56]

In a systematic review, magnetic sphincter augmentation appeared to reinforce the lower esophageal sphincter to antireflux, effectively reducing the time percentage of esophageal acid exposure (pH <  4), improving the GERD health-related quality of life score, reducing the operative time (vs Nissen fundoplication), and achieving similar treatment success as that of fundoplication. ^[57] These findings suggest that magnetic sphincter augmentation may have potential as an alternative surgical option for patients with conservative GERD treatment failure. ^[57]

Schizas et al conducted a systematic review of 35 studies that evaluated the safety and efficacy of magnetic sphincter augmentation (MSA) using the LINX® Reflux Management System. A total of 2511 patients were included and analyzed; the majority of patients reported complete resolution of their GERD symptoms. All patients discontinued PPI therapy and experienced less bloating and a better ability to blech or vomit compared to laparoscopic fundoplication. Encouraging results were also noted in bariatric patients as well as patients with large hiatal hernias. ^[58]