Gastroesophageal Reflux — "What’s Up?"
Special Report
Gastroesophageal Reflux—"What’s Up?"
By A. Craig Hillemeier, MD, FAAP
Many pediatricians will remember the day when most infants had problems with "spitting up." Sometime in the last couple of decades the terminology has changed and these infants are now said to be afflicted with gastroesophageal reflux. The medical literature has exploded with literally hundreds of articles describing ways to quantify gastroesophageal reflux, conditions that are caused by this disorder, and therapies for what is viewed as an increasingly prevalent problem.
It is common for infants to have recurrent symptoms of daily spitting up or vomiting during their first year of life. There is a wide variation of these symptoms, from the occasional wet burp to persistent emesis. A thorough evaluation of most of these infants reveals no definable anatomic, metabolic, infectious, or neurologic etiology. These infants are then labeled with the descriptive term gastroesophageal reflux, which in its simplest form merely means the presence of gastric contents proximal to the stomach. Since almost any infant has at least some symptoms of gastroesophageal reflux, it is tempting to speculate that there is a cause-and-effect relationship between almost any illness and gastroesophageal reflux. However, the conditions that will benefit from the myriad of tests that assist in identifying which children deserve aggressive therapy for their gastroesophageal reflux are indeed limited. This review will examine some of the newer studies of the physiology, diagnosis, and treatment of gastroesophageal reflux during infancy.
The upper gastrointestinal tract distal to the mid-esophagus is composed of smooth muscle and is not under voluntary control. The esophagus functions as a muscular tube, and the band of muscle at the distal esophagus is known as a lower esophageal sphincter. This muscle, circular in its orientation, remains tonically contracted, thus acting as a lid to the contents of the stomach. Many of us remember physiology class, where we were told that the reason gastric contents kept refluxing back past this barrier in infants was because this muscle was weak. The theory was that since infants were generally small and weak, their lower esophageal sphincter was also rather diminutive and weak. However, it has been shown that the stress-generating characteristics of the lower esophageal sphincter during infancy are actually higher than during the adult years. Recent studies have shown that most episodes of gastroesophageal reflux during infancy and childhood are indeed due to inappropriate relaxation of this muscle. In other words, the lower esophageal sphincter not only relaxes during swallowing, it also relaxes inappropriately when the stomach is full of food. In the absence of a normal swallow, this relaxation of the lower esophageal sphincter allows food to regurgitate into the esophagus (i.e., spitting up).1 This inappropriate relaxation of the lower esophageal sphincter is likely due to an abnormal neuronal reflex. It is unclear why this abnormal reflex should cause symptoms more frequently during the newborn period. This would explain why medications that primarily increase lower esophageal sphincter tones such as bethanechol have not been found to be effective in treating gastroesophageal reflex. It is possible that, in the future, medications will be developed that decrease the incidence of inappropriate relaxations of lower esophageal sphincter but at present none is available.
The list of conditions that have been claimed to be caused by gastroesophageal reflux is long and many of these relationships are poorly established. Unfortunately, the relationship between gastroesophageal reflux and pulmonary disease remains difficult to establish in an individual case. In a child with recurrent pneumonia and proven reflux by pH probe, lipid-laden macrophages aspirated from the bronchial tree may indicate those children who are suffering from significant aspiration. It is challenging in a child with recurrent bronchospasm who has gastroesophageal reflux to determine if aggressive therapy with acid-suppressing agents or a fundoplication will be helpful, and patients with asthma and proven reflux may benefit from therapeutic trials.
One of the conditions that has received a lot of interest in the last few years with respect to gastroesophageal reflux has been the "colicky baby." There are several studies that demonstrate that colic in most infants is not related to gastroesophageal reflux. It does not appear that fussy behavior in infants is commonly related to reflux. However, there are rare infants who have episodes of discomfort during feedings who respond to empiric therapy for esophagitis. However, if a therapeutic dose (e.g., zantac, 2 mg/kg bid) is maintained and there is no relief, it is unlikely that the problem is related to gastroesophageal reflux and associated esophagitis.
In addition to recurrent pneumonia and asthma, there have been other disorders of the upper airway that have been claimed to be caused by gastroesophageal reflux. Persistent recurrent cough, stridor, and subglottic stenosis are disorders that may well in many instances deserve an evaluation by a pediatric gastroenterologist specialist to determine if the child really has significant reflux.2 Many of these children may benefit from aggressive medical and even surgical therapy.
The therapy of gastroesophageal reflux has seen some changes in the last few years. It should be remembered that a healthy, thriving infant who has no adverse sequelae from his or her "spitting up" probably needs no diagnostic tests other than a thorough history and physical examination and requires no specific pharmacological or surgical therapy. Parental reassurance and perhaps modification of feeding habits are usually sufficient. Smaller, more frequent feeding and increased solids may give some benefit. Positional therapy is not a very effective therapeutic modality. There are some data to demonstrate that the prone position with the head elevated does reduce the amount of gastroesophageal reflux. The epidemiologic data that suggest an increased incidence of sudden infant death syndrome (SIDS) in young infants sleeping in the prone position has resulted in general abandonment of positional therapy.
Keeping in mind that there is no specific pharmacological therapy for inappropriate relaxation of the lower esophageal, it is not surprising that most pharmacological therapies have not been met with resounding success. A medication increasingly used to treat gastroesophageal reflux during infancy over the last few years has been cisapride. It has been estimated that more than 140 million courses of cisapride have been prescribed over the past 10 years in North America and Europe, many of these in childhood. Cisapride is a gastrointestinal prokinetic agent that increases motility events such as gastric emptying and acts as a post-ganglionic serotonin receptor agonist. It does not have the frequent and distasteful central nervous system side effects seen with metoclopramide.3
It is not clear whether cisapride is effective in treating gastroesophageal reflux during infancy. A literature review of cisapride treatment efficacy could certainly conclude that cisapride results in some improvement in infants with gastroesophageal reflux.4 However, whether this improvement is enough to justify the widespread use of cisapride is not clear, and there are certainly many infants with gastroesophageal reflux who show no improvement with cisapride.
A child with a serious medical condition resulting from gastroesophageal reflux deserves aggressive treatment for gastroesophageal reflux. That treatment may include a trial of cisapride and effective acid suppression prior to fundoplication. The side effects of cisapride are usually rare, transitory, and benign. The major side effect that has concerned people regarding the use of cisapride is the possibility of adverse cardiac effects, especially the prolongation of the QTc interval and resulting arrhythmias. This risk is thought to be increased in young preterm infants in whom the hepatic cytochrome enzyme, which is important for the metabolism of cisapride, appears to have diminished activities. By 6-12 months, this enzyme level increases to normal levels. The incidence of cardiac arrhythmias associated with cisapride has been estimated at less than 1 in 11,000 premature infants and most of the reported arrhythmias have been associated with overdosage or use with concurrent medications now known to be contraindicated when cisapride is used.5 In June 1998, Janssen Pharmaceutical issued an announcement that the labeling for cisapride was reflecting increased warnings in the use of the drug resulting in adverse cardiac events. The North American Society of Pediatric Gastroenterology has recommended that if cisapride is used, precautions should be taken to minimize the risk of associated arrhythmias. These include: 1) avoiding medications that compete with it for the hepatic enzyme (erythromycin and clarithromycin and the azole antifungals); 2) dosage should be limited to 0.8 mg per kg per day divided into 3-4 doses in a 24-hour period; 3) avoiding use of the drug in patients with acute illness that might result in electrolyte abnormalities and in patients who are known to have symptoms of cardiac conduction abnormalities. There may be some small therapeutic benefit to be derived from cisapride therapy in appropriately chosen patients but when it is used it should be used with appropriate caution and monitoring.
The second major therapeutic advance that has been made over the past few years in the treatment of gastroesophageal refluxes is laproscopic fundoplication.5 This procedure has become common in many pediatric centers. While it results in a slight increase in operating room time compared to conventional surgery, it results in markedly decreased duration of hospitalization and perhaps a decreased incidence of postoperative adhesions.
There is some justification to the point of view that many physicians express when they compare the gastroesophageal reflux saga over the last 20-30 years to Shakespeare’s play "Much Ado About Nothing." Despite this prevalent opinion, there are some children who have serious medical problems associated with or exacerbated by gastroesophageal reflux and recent advances in diagnosis and treatment have the potential to decrease morbidity associated with this problem.
References
1. Omari TI, et al. Mechanisms of gastroesophageal reflux in healthy premature infants. J Pediatr 1998; 133:650-654.
2. Yellon RF. The spectrum of reflux-associated otolaryngologic problems in infants and children. Am J Med 1997;103(3S):125S-129S.
3. Shulman RJ, et al. A medical position statement of the North American Society for Pediatric Gastroenterology and Nutrition: The use of cisapride in children. J Pediatr Gastroenterol Nutr 1999;28:529-533.
4. Cohen RC, et al. Cisapride in the control of symptoms in infants with gastroesophageal reflux: A randomized, double-blind, placebo-controlled trial. J Pediatr 1999; 134:287-292.
5. Ward RM, et al. Cisapride: A survey of the frequency and use and adverse events in premature newborns. Pediatrics 1999;103:469-472.
Gastroesophageal reflux:
a. is an established cause for infantile colic in many babies.
b. results from a relative weakness of the distal esophageal sphincter.
c. symptoms can be improved in some infants by treatment with the GI prokinetic agent cisapride.
d. can be safely treated with cisapride in an infant also receiving azithromycin.
Subscribe Now for Access
You have reached your article limit for the month. We hope you found our articles both enjoyable and insightful. For information on new subscriptions, product trials, alternative billing arrangements or group and site discounts please call 800-688-2421. We look forward to having you as a long-term member of the Relias Media community.