Background: Gastroesophageal reflux is a normal physiologic phenomenon experienced intermittently by most people, particularly after a meal. Gastroesophageal reflux disease (GERD) occurs when the amount of gastric juice that refluxes into the esophagus exceeds the normal limit, causing symptoms with or without associated esophageal mucosal injury (esophagitis).

History: GERD can cause typical (esophageal) or atypical (extraesophageal) symptoms.

• Typical symptoms include the following:

• Heartburn: This is the most common symptom. It is felt as a retrosternal sensation of burning or discomfort that occurs usually after eating or when lying down or bending over.

• Regurgitation: This is effortless return of gastric and/or esophageal contents into the pharynx. It can induce respiratory complications if gastric contents spill into the tracheobronchial tree.

• Dysphagia: This occurs in approximately one third of patients due to a mechanical stricture or a functional problem (nonobstructive dysphagia secondary to abnormal esophageal peristalsis). Patients feel that food is stuck, particularly in the retrosternal area.

• Atypical symptoms include the following:

• Cough and/or wheezing: These are respiratory symptoms resulting from aspiration of gastric contents into the tracheobronchial tree or from the vagal reflex arc producing bronchoconstriction. Approximately 50% of patients who have GERD-induced asthma do not experience heartburn.

• Hoarseness: This results from irritation of the vocal cords by gastric refluxate. It often is experienced in the morning.

• Chest pain: Reflux is the most common cause of noncardiac chest pain and accounts for approximately 50% of cases. Patients can present to the emergency department with pain resembling myocardial infarction. Reflux should be ruled out (if necessary using esophageal manometry and 24-h pH testing) once a cardiac cause has been excluded. Alternatively, a therapeutic trial of high-dose proton pump inhibitor therapy can be tried.

• Importantly, a diagnosis of GERD based on the presence of typical symptoms is correct in only 70% of patients.

Physical:

• Noncontributory

Imaging Studies:

• Barium esophagogram

• This study is particularly important for patients who experience dysphagia.

• It can show the presence and the location of a stricture and the presence and shape of a hiatal hernia.

• Esophagogastroduodenoscopy

• Esophagogastroduodenoscopy (EGD) identifies the presence and severity of esophagitis and the possible presence of Barrett esophagus.

• EGD also excludes the presence of other diseases that can present similarly, such as a peptic ulcer.

• Although EGD frequently is performed to diagnose GERD, this is not the most cost-effective diagnostic strategy because esophagitis is present in only 50% of patients with GERD.

Other Tests:

• Esophageal manometry

• This study defines the function of the LES and esophageal body (peristalsis).

• It is essential for correctly positioning the probe for the 24-hour pH monitoring.

• Ambulatory 24-hour pH monitoring

• This test is the criterion standard for diagnosis of GERD, with a sensitivity of 96% and a specificity of 95%.

• The test quantifies the gastroesophageal reflux and allows a correlation between symptoms and episodes of reflux.

• Patients with endoscopically confirmed esophagitis do not need pH testing for diagnosis of GERD.

• Indications for esophageal manometry and prolonged pH monitoring include the following:

• Persistence of symptoms while taking adequate antisecretory therapy such as proton pump inhibitor therapy

• Recurrence of symptoms after discontinuation of acid-reducing medications

• Investigation of atypical symptoms such as chest pain or asthma in patients without esophagitis

• To confirm the diagnosis in preparation for antireflux surgery

• Radionuclide measurement of gastric emptying

• Although delayed gastric emptying is present in as many as 60% of patients, it usually is a minor factor in the pathogenesis of the disease in most patients (except those with advanced diabetes mellitus or connective tissue disorders).

• Patients with delayed emptying typically experience postprandial bloating and fullness in addition to the other symptoms.
  
  

• Lose weight (if overweight).

• Avoid alcohol, chocolate, citrus juice, and tomato-based products.

• Avoid large meals.

• Wait 3 hours after a meal before lying down.

• Elevate head of bed 8 inches.

• Pharmacological therapy

• Antacids were the standard treatment in the 1970s and are effective in controlling mild symptoms. Administer after each meal and at bedtime.

• Histamine-2 receptor antagonists are the first line of treatment for patients with mild-to-moderate symptoms and grade I-II esophagitis. They are effective for healing only mild esophagitis in 70-80% of patients and for maintenance therapy to prevent relapse. Tachyphylaxis has been observed, suggesting that pharmacological tolerance can reduce the long-term efficacy of these drugs.

• Additional H2 blocker therapy has been reported to be useful in the rare patient with very severe disease (particularly when Barrett esophagus is present) who has nocturnal acid breakthrough.

• Proton pump inhibitors are the most powerful medications available. They should be used only when GERD has been objectively documented. They work by blocking the final step in the H+ ion secretion by the parietal cell. They have few adverse effects and are well tolerated for long-term use.

• Prokinetic agents improve the motility of the esophagus and stomach. They are somewhat effective but only in patients with mild symptoms; others usually require additional acid-suppressing medications such as proton pump inhibitors. Long-term prokinetic agent use may have serious, even potentially fatal, complications and should be discouraged.

Surgical Care: Approximately 80% of patients have a recurrent but nonprogressive form of the disease that is controlled with medications. 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 these patients, surgical treatment should be considered at an earlier stage to avoid the sequelae of the disease that can have serious consequences.

• Indications for fundoplication include the following:

• Patients with symptoms incompletely controlled by proton pump inhibitor therapy can be considered for surgery. Surgery also can be considered in patients with well-controlled disease 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.

• Presence of extraesophageal manifestations of GERD may indicate the need for surgery. These include (1) respiratory manifestations (cough, wheezing, aspiration); (2) ear, nose, and throat manifestations (hoarseness, sore throat, otitis media); and (3) dental manifestations (enamel erosion).

• Laparoscopic fundoplication

• The operation is performed under general endotracheal anesthesia. Five small incisions are used (5-10 mm). The fundus of the stomach is wrapped around the esophagus to create a new valve at the level of the gastroesophageal junction.

• The essential elements of the operation are as follows:
  • Reduction of the hiatal hernia

  • 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.)

• The operation lasts 2-2.5 hours. Hospital stay is approximately 2 days, and patients resume regular activities within 2-3 weeks.

• Resolution of symptoms is obtained in approximately 94% of patients.

The goal of pharmacotherapy is to prevent complications and reduce morbidity.

Drug Category: H2 receptor antagonists -- These agents are reversible competitive blockers of histamine at the H2 receptors, particularly those in the gastric parietal cells where they inhibit acid secretion. The H2 antagonists are highly selective, do not affect the H1 receptors, and are not anticholinergic agents. Although IV administration of H2 blockers may be used to treat acute complications (eg, GI bleeding), the benefits are not yet proven.

Drug Name	Ranitidine (Zantac) -- Inhibits histamine stimulation of the H2 receptor in gastric parietal cells, which, in turn, reduces gastric acid secretion, gastric volume, and hydrogen concentrations.
Adult Dose	150 mg PO bid (300 mg PO bid or 150 mg qid)
Pediatric Dose	<12 years: Not established >12 years PO: 1.25-2.5 mg/kg/dose q12h; not to exceed 300 mg/d IV/IM: 0.75-1.5 mg/kg/dose q6-8h; not to exceed 400 mg/d
Contraindications	Documented hypersensitivity
Interactions	May decrease effects of ketoconazole and itraconazole; may alter serum levels of ferrous sulfate, diazepam, nondepolarizing muscle relaxants, and oxaprozin
Pregnancy	B - Usually safe but benefits must outweigh the risks.
Precautions	Caution in renal or liver impairment; if changes in renal function occur during therapy, consider adjusting dose or discontinuing treatment

Drug Name	Cimetidine (Tagamet) -- Inhibits histamine at H2 receptors of gastric parietal cells, which results in reduced gastric acid secretion, gastric volume, and hydrogen concentrations.
Adult Dose	400 mg PO bid (800 mg bid or 400 mg PO qid)
Pediatric Dose	Not established Suggested dose is 1-2 mg/kg/d PO/IV divided q6h; not to exceed 40 mg/d
Contraindications	Documented hypersensitivity
Interactions	Can increase blood levels of theophylline, warfarin, tricyclic antidepressants, triamterene, phenytoin, quinidine, propranolol, metronidazole, procainamide, and lidocaine
Pregnancy	B - Usually safe but benefits must outweigh the risks.
Precautions	Elderly may experience confusional states; may cause impotence and gynecomastia in young males; may increase levels of many drugs; adjust dose or discontinue treatment if changes in renal function occur

Drug Name	Famotidine (Pepcid) -- Competitively inhibits histamine at H2 receptor of gastric parietal cells, resulting in reduced gastric acid secretion, gastric volume, and hydrogen concentrations.
Adult Dose	20 mg PO bid (40 mg bid)
Pediatric Dose	Not established; 1-2 mg/kg/d PO/IV divided q6h suggested; not to exceed 40 mg/dose
Contraindications	Documented hypersensitivity
Interactions	May decrease effects of ketoconazole and itraconazole
Pregnancy	B - Usually safe but benefits must outweigh the risks.
Precautions	If changes in renal function occur during therapy, consider adjusting dose or discontinuing treatment

Drug Name	Nizatidine (Axid) -- Competitively inhibits histamine at the H2 receptor of the gastric parietal cells, resulting in reduced gastric acid secretion, gastric volume, and hydrogen concentrations.
Adult Dose	150 mg PO bid (300 mg PO qhs)
Pediatric Dose	Not established
Contraindications	Documented hypersensitivity
Interactions	None reported
Pregnancy	C - Safety for use during pregnancy has not been established.
Precautions	Caution in renal or liver impairment; if changes in renal function occur during therapy, consider adjusting dose or discontinuing treatment

Drug Category: Proton pump inhibitors -- Inhibit gastric acid secretion by inhibition of the H+/K+/ATP-ase enzyme system in the gastric parietal cells. These agents are used in cases of severe esophagitis and in patients not responding to H2-antagonist therapy.

Drug Name	Omeprazole (Prilosec) -- Used for up to 4 wk to treat and relieve symptoms of active duodenal ulcers. May use for up to 8 wk to treat all grades of erosive esophagitis.
Adult Dose	20 mg PO qd or bid
Pediatric Dose	Not established
Contraindications	Documented hypersensitivity
Interactions	May decrease effects of itraconazole and ketoconazole; may increase toxicity of warfarin, digoxin, and phenytoin
Pregnancy	C - Safety for use during pregnancy has not been established.
Precautions	Bioavailability may increase in the elderly

Drug Name	Lansoprazole (Prevacid) -- Inhibits gastric acid secretion. Used for up to 8 wk to treat all grades of erosive esophagitis.
Adult Dose	15-60 mg PO qd or 15 mg bid
Pediatric Dose	Not established
Contraindications	Documented hypersensitivity
Interactions	May decrease effects of ketoconazole and itraconazole; may increase theophylline clearance
Pregnancy	C - Safety for use during pregnancy has not been established.
Precautions	Consider adjusting dose in liver impairment

Drug Name	Rabeprazole (Aciphex) -- For short-term (4-8 wk) treatment and relief of symptomatic erosive or ulcerative GERD. In patients not healed after 8 wk, consider additional 8-wk course.
Adult Dose	20 mg PO qd for 4-8 wk
Pediatric Dose	Not established
Contraindications	Documented hypersensitivity
Interactions	None reported
Pregnancy	C - Safety for use during pregnancy has not been established.
Precautions	Symptomatic response does not exclude possibility of malignancy

Drug Name	Esomeprazole (Nexium) -- S-isomer of omeprazole. Inhibits gastric acid secretion by inhibiting H+/K+ ATPase enzyme system at secretory surface of gastric parietal cells.
Adult Dose	20-40 mg PO qd for 4-8 wk
Pediatric Dose	Not established
Contraindications	Documented hypersensitivity
Interactions	None reported
Pregnancy	C - Safety for use during pregnancy has not been established.
Precautions	Symptomatic relief with proton pump inhibitors may mask symptoms of gastric malignancy

Drug Category: Prokinetics -- Increase lower esophageal sphincter pressure helping to reduce reflux of gastric contents. They also accelerate gastric emptying.

Drug Name	Metoclopramide (Reglan) -- Works as antiemetic by blocking dopamine receptors in the chemoreceptor trigger zone of the CNS.
Adult Dose	10 mg PO qid
Pediatric Dose	Not established
Contraindications	Documented hypersensitivity; pheochromocytoma or GI hemorrhage, obstruction, or perforation; history of seizure disorders
Interactions	May antagonize effects of metoclopramide; opiate analgesics may increase metoclopramide toxicity in CNS
Pregnancy	B - Usually safe but benefits must outweigh the risks.
Precautions	Caution in history of mental illness and Parkinson disease

• Barrett esophagus

• This is one of the most serious complications of GERD because it may progress to cancer. Even though a prospective randomized trial comparing proton pump inhibitors to laparoscopic fundoplication has never been performed, the authors believe fundoplication is preferable for the following reasons:

• Proton pump inhibitors, 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, and these patients are 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 continue to undergo periodic surveillance endoscopy even after laparoscopic fundoplication.

• Respiratory complications include pneumonia, asthma, and interstitial lung fibrosis.

Prognosis:

• Most patients do very well with medications, although relapse after cessation of medical therapy is common and indicates the need for chronic maintenance therapy.

• Identifying the subgroup of patients who may develop the most serious complications of the disease and treating them aggressively is important. Surgery at an early stage most likely is indicated in these patients.

• After a laparoscopic Nissen fundoplication, resolution of symptoms is obtained in approximately 94% of patients.

• Achalasia can present with heartburn. Only esophageal manometry and pH monitoring allow distinction of the 2 diseases, for which therapy is completely different.

Caption: Picture 2. Gastroesophageal reflux disease/Barrett esophagus/adenocarcinoma sequence

Caption: Picture 3. Barium swallow indicating hiatal hernia

Caption: Picture 4. Ambulatory pH monitoring indicating episodes of reflux correlating with the heartburn experienced by the patient

Caption: Picture 5. Laparoscopic Nissen fundoplication

REFERENCES

• Bremner RM, Bremner CG, DeMeester TR: Gastroesophageal reflux: the use of pH monitoring. Curr Probl Surg 1995 Jun; 32(6): 429-558.
• Broussard CN, Richter JE: Treating gastro-oesophageal reflux disease during pregnancy and lactation: what are the safest therapy options? Drug Saf 1998 Oct; 19(4): 325-37.
• Bytzer P, Havelund T, Hansen JM: Interobserver variation in the endoscopic diagnosis of reflux esophagitis. Scand J Gastroenterol 1993 Feb; 28(2): 119-25.
• Campos GM, Peters JH, DeMeester TR: Multivariate analysis of factors predicting outcome after laparoscopic Nissen fundoplication. J Gastrointest Surg 1999 May-Jun; 3(3): 292-300.
• Costantini M, Crookes PF, Bremner RM: Value of physiologic assessment of foregut symptoms in a surgical practice. Surgery 1993 Oct; 114(4): 780-6; discussion 786-7.
• Fuchs KH, DeMeester TR, Albertucci M: Specificity and sensitivity of objective diagnosis of gastroesophageal reflux disease. Surgery 1987 Oct; 102(4): 575-80.
• Harding SM, Richter JE, Guzzo MR: Asthma and gastroesophageal reflux: acid suppressive therapy improves asthma outcome. Am J Med 1996 Apr; 100(4): 395-405.
• Hetzel DJ, Dent J, Reed WD: Healing and relapse of severe peptic esophagitis after treatment with omeprazole. Gastroenterology 1988 Oct; 95(4): 903-12.
• Hinder RA, Stein HJ, Bremner CG: Relationship of a satisfactory outcome to normalization of delayed gastric emptying after Nissen fundoplication. Ann Surg 1989 Oct; 210(4): 458-64; discussion 464-5.
• Hunter JG, Trus TL, Branum GD: A physiologic approach to laparoscopic fundoplication for gastroesophageal reflux disease. Ann Surg 1996 Jun; 223(6): 673-85; discussion 685-7.
• Kauer WK, Peters JH, DeMeester TR: Mixed reflux of gastric and duodenal juices is more harmful to the esophagus than gastric juice alone. The need for surgical therapy re- emphasized. Ann Surg 1995 Oct; 222(4): 525-31; discussion 531-3.
• Koelz HR, Birchler R, Bretholz A: Healing and relapse of reflux esophagitis during treatment with ranitidine. Gastroenterology 1986 Nov; 91(5): 1198-205.
• McCallum RW, Berkowitz DM, Lerner E: Gastric emptying in patients with gastroesophageal reflux. Gastroenterology 1981 Feb; 80(2): 285-91.
• Monnier P, Ollyo JB, Fontolliet C: Epidemiology and Natural History of Reflux Esophagitis. Seminars in Laparoscopic Surgery 1995; 2: 2-9.
• Ollyo JB, Lang F, Fontolliet Ch: Savary-Miller's new endoscopic grading of reflux-oesophagitis: A simple, reproductible, logical, complete and useful classification. Gastroenterology 98: A100.
• Patti MG, Arcerito M, Feo CV: An analysis of operations for gastroesophageal reflux disease: identifying the important technical elements. Arch Surg 1998 Jun; 133(6): 600-6; discussion 606-7.
• Patti MG, Feo CV, De Pinto M: Results of laparoscopic antireflux surgery for dysphagia and gastroesophageal reflux disease. Am J Surg 1998 Dec; 176(6): 564-8.
• Patti MG, Arcerito M, Feo CV: Barrett's esophagus: a surgical disease. J Gastrointest Surg 1999 Jul-Aug; 3(4): 397-403; discussion 403-4.
• Peghini PL, Katz PO, Castell DO: Ranitidine controls nocturnal gastric acid breakthrough on omeprazole: a controlled study in normal subjects. Gastroenterology 1998 Dec; 115(6): 1335-9.
• Peters JH, DeMeester TR, Crookes P: The treatment of gastroesophageal reflux disease with laparoscopic Nissen fundoplication: prospective evaluation of 100 patients with "typical" symptoms. Ann Surg 1998 Jul; 228(1): 40-50.
• Porro GB, Pace F, Peracchia A: Short-term treatment of refractory reflux esophagitis with different doses of omeprazole or ranitidine. J Clin Gastroenterol 1992 Oct; 15(3): 192-8.
• Richter JE: Extraesophageal presentations of gastroesophageal reflux disease. Semin Gastrointest Dis 1997 Apr; 8(2): 75-89.
• Spechler SJ: Epidemiology and natural history of gastro-oesophageal reflux disease. Digestion 1992; 51 Suppl 1: 24-9.
• Spechler SJ: The columnar-lined esophagus. History, terminology, and clinical issues. Gastroenterol Clin North Am 1997 Sep; 26(3): 455-66.
• Streitz JM Jr, Andrews CW Jr, Ellis FH Jr: Endoscopic surveillance of Barrett's esophagus. Does it help? J Thorac Cardiovasc Surg 1993 Mar; 105(3): 383-7; discussion 387-8.
• Streitz JM Jr, Williamson WA, Ellis FH Jr: Current concepts concerning the nature and treatment of Barrett's esophagus and its complications. Ann Thorac Surg 1992 Sep; 54(3): 586-91.
• Vigneri S, Termini R, Leandro G: A comparison of five maintenance therapies for reflux esophagitis. N Engl J Med 1995 Oct 26; 333(17): 1106-10.

  MEDCEU Continuing Education Courses CEU for Nurses and Healthcare Professional

   Home Page