2.1 Definitions 

Gastroesophageal reflux is the apparently effortless passage of gastric contents into the esophagus due to impairment of the antireflux mechanism at the gastroesophageal junction. Reflux is facilitated by the presence of a gradient in pressure between the positive pressure within the abdominal cavity and the negative pressure within the intrathoracic cavity. Vomiting, however, is a complex coordinated reflex mechanism that may occur in response to a variety of stimuli and results in forceful expulsion of gastric contents through the mouth. The vomiting reflex is controlled by the nervous system, specifically via the vomiting center in the brainstem.

2.2.1 INTRODUCTION

The approach to the vomiting child is one of the most difficult problems in pediatrics, as the differential diagnosis is not limited to the gastrointestinal tract and includes conditions that are pediatric emergencies. In addition, persistent vomiting can lead to complications such as dehydration, electrolyte abnormalities, Mallory-Weiss tears and aspiration of gastric contents. The following comments on history, examination, diagnosis and management provide guidance as to the approach to the vomiting child, but cannot substitute for a broad knowledge of pediatrics and clinical experience that allows differentiation of the sick child from the child that is less unwell.

A number of features of the history are particuarly helpful in reaching a diagnosis:

Vomiting in the neonatal and early infant period may frequently be due to structural abnormalities of the bowel, inborn errors of metabolism and withdrawal secondary to maternal drug addictions (Table 1). A complete history of the pregnancy (including drug history, past pregnancies and abortions), delivery and postpartum period is vital. Some conditions will occur in specific age ranges: pyloric stenosis at 2 to 8 weeks of age; intussusception at 3 to 18 months. Appendicitis is rare before the age of 12 months. In older children, other conditions, especially gastroenteritis, otitis media and respiratory tract infections are more common.

Food allergy, the most common cause being cow's milk protein intolerance, occurs primarily in formula-fed infants. Infant celiac disease presents only after prolonged exposure to gluten in the diet. Enzyme-deficiency diseases such as galactosemia and fructosemia manifest only after the introduction of the offending sugar into the diet.

Bile-stained vomitus suggests intestinal obstruction distal to the second part of the duodenum, while hematemesis suggests esophageal, gastric or duodenal mucosal disease.

Acute onset and short duration suggest a transient illness, while a longer history of vomiting suggests chronic disease, especially if associated with growth failure.

Diarrhea is a common feature accompanying gastrointestinal infection, but some looseness of stools can be found in association with other conditions such as urinary tract infections. A bloody stool resembling red currant jelly is seen classically in intussusception. If abdominal pain is present, the nature, severity and location are important. Obstruction of the GI tract often presents with central, colicky, intermittent pain, as do the cramps of gastroenteritis. Colicky pain may be accompanied by pallor, especially in intussusception. Other conditions are associated with a more constant pain, or pain in specific locations -eg., in the right iliac fossa with appendicitis, epigastric/central pain radiating to the back with pancreatitis. Fever suggests an infectious origin, and foci outside the GI tract as in meningitis should be considered. Neurological symptoms such as headache, confusion and loss of developmental skills may indicate a primary CNS pathology.

A complete physical assessment is required, for it is important to determine whether the child is well or sick. An initial assessment is often possible by careful observation from the end of the bed. The height, weight and head circumference should be plotted (with past recordings if possible) on a growth chart to determine whether there has been a fall-off in recent months. A rapidly expanding head circumference suggests intracranial pathology. An assessment of dehydration (including tissue turgor, mucous membranes, capillary return, pulse and blood pressure) as well as a thorough examination of each system is essential. When examining the abdomen, it is particularly important to detect any distention, masses, tenderness and especially rigidity or guarding that suggests the need for urgent surgical review.

Investigation of the vomiting child is dependent on the history and the results of physical examination. An acutely ill febrile neonate requires different investigation than an older child. Investigation may include:

A complete blood count may show an elevated white cell count with infection or inflammation, but is relatively nonspecific. Anemia may be present and be secondary to an acute bleed, or be of a long-term nature in the presence of chronic disease (normochromic) or ongoing blood loss (hypochromic, microcytic). Electrolytes, urea, creatinine and anion gap provide information regarding fluid balance and metabolic status. Generally, frequent vomiting results in hypochloremic, hypokalemic alkalosis; however, acidosis may occur if dehydration is severe or secondary to an underlying metabolic disorder. Abnormalities of urea are found in dehydration (high) and in urea cycle disorders (low). Hypo- or hypernatremia may occur if inappropriate fluid replacement is given.

Any child with symptoms that suggest a surgical problem such as intestinal obstruction requires an urgent radiograph of the abdomen with both supine and erect films. Intestinal obstruction is suggested by dilated loops of bowel with air-fluid levels, although a similar appearance can occur with an ileus accompanying gastroenteritis. The history and examination usually allow differentiation. Other conditions have more specific appearances, such as the right upper quadrant mass in intussusception, the double-bubble appearance of duodenal atresia and a distended loop of bowel with volvulus. An abdominal ultrasound may be of help in the diagnosis of pyloric stenosis (hypertrophic mass at outlet of stomach), liver disease (gallstones and thickened gallbladder wall in cholecystitis, liver enlargement in hepatitis), pancreatitis (swollen, edematous pancreas), renal disease (hydronephrosis or small kidneys). A child who presents with persistent bile-stained emesis requires an upper GI contrast study to exclude anatomical causes of obstruction including intestinal malrotation, webs, rings and strictures. The contrast study may include a follow-through of the small intestine to identify more distal problems such as terminal Crohn's disease.

Urinalysis is important to exclude urinary pathology such as infection. Stool examinations for bacterial culture, ova and parasites, and viruses are indicated if diarrhea is present, and for Clostridium difficile toxin if there is a recent history of antibiotic use. In the severely ill and/or febrile child with emesis and suspected sepsis or meningitis, cultures of the blood and cerebrospinal fluid are required.

Upper gastrointestinal endoscopy may be employed to exclude mucosal disease in the esophagus (esophagitis), stomach (H. pylori gastritis, ulceration) or duodenum (ulceration, Crohn's disease, celiac disease).

Management of the vomiting child centers on establishing an accurate diagnosis and stabilizing the patient's condition with regard to fluid and electrolyte abnormalities. Specific conditions require specific treatment, such as surgery for appendicitis and antibiotics for meningitis. Acute management of dehydration requires an accurate assessment as mild (<5%), moderate (5-10%) or severe (>10%). Fluid requirements are then calculated to replace the deficit (usually over 8, 12 or 24 hours), provide maintenance fluids (age-dependent), and replace continuing GI losses. Mild to moderate dehydration can usually be managed via the oral route unless contraindicated (e.g., preoperative conditions such as appendicitis or intestinal obstruction), while severe dehydration usually requires intravenous replacement, often with colloid as well as crystalloid solutions.

2.3.1 INTRODUCTION

Effortless reflux of stomach contents is noted in approximately 50% of healthy newborn infants. In the majority of affected children it resolves over the first year of life, especially in the second six months when the dietary intake of solids increases and sitting and standing are achieved. In all children, occasional reflux after a meal is a normal event. Pathological reflux is defined as being secondary to an underlying disorder or when the reflux is complicated by failure to thrive, esophagitis or respiratory conditions such as asthma or aspiration pneumonia.

Reflux of gastric contents into the esophagus is prevented by the antireflux mechanism at the gastroesophageal junction, which consists primarily of the diaphragmatic crura and the lower esophageal sphincter (LES). The LES is a physiologically defined region of the lower esophagus that is maintained in a partial contractile condition to create a high-pressure zone, but relaxes as part of the swallowing reflex to allow food passage into the stomach. The primary cause of reflux is transient relaxation of the LES unrelated to swallowing, rather than a consistently low pressure of the sphincter. Although gastric volume and composition of gastric contents are important influences, the mechanism of this transient relaxation is not understood. Other factors important in the prevention of complications of reflux include esophageal peristalsis, which clears refluxed contents from the esophagus; salivary secretions, which assist in neutralizing refluxed gastric acid; esophageal mucosal resistance; and the protective pulmonary reflexes that prevent reflux into the respiratory tree.

A thorough history and physical examination are required to establish if possible whether the child is refluxing or vomiting. Gastroesophageal reflux is often effortless and vomiting forceful, but some overlap occurs. The onset of gastroesophageal reflux in infants is usually soon after birth. A sudden onset of reflux in a child with no past history or bilious emesis requires a search for a secondary cause. Feeding history is important. Feeds of inappropriately large volume are more likely to be refluxed. The physician should always determine whether the child is otherwise well and if not, identify symptoms or signs that suggest an underlying disorder or predispose to reflux or vomiting (Table 1). The frequency and volume of the reflux episodes should be established and any symptoms or signs of complications of gastroesophageal reflux sought.

2.3.4.1 Failure to thrive

Failure to thrive occurs in association with gastroesophageal reflux when caloric intake is insufficient as a result of the loss of milk through reflux, or when children with esophagitis limit intake due to pain or dysphagia associated with feeding.

Esophagitis may be indicated by dysphagia, hematemesis, anemia, hypoalbuminemia and thrombocytosis. While dysphagia may occur secondary to esophageal ulceration or strictures, it may also be secondary to the impaired motility that is associated with esophagitis and often presents as food sticking.

Aspiration of gastric contents causing pneumonia is relatively common in the neurologically impaired child, but aspiration of food during its ingestion may also occur as a result of incoordinate swallowing. Some children with asthma, especially nocturnal asthma, may have symptoms secondary to reflux. Gastroesophageal reflux is a less common cause of apnea in premature infants, most apnea in this age group being of central origin. Gastroesophageal reflux is not responsible for SIDS.

The vast majority of infants with gastroesophageal reflux do not require additional investigation. Infants whose reflux is persistent, severe or associated with symptoms or signs of an underlying disorder require further investigation. Initial investigations should include a complete blood count, electrolytes, urea, anion gap, urinalysis and, in older infants, liver function tests and a lipase or amylase. An upper gastrointestinal contrast study (upper GI) should be performed to exclude predisposing anatomic abnormalities such as malrotation or strictures. Reflux seen during this test is a poor indicator of pathologic reflux. If the infant or child is suspected of having a complication of gastroesophageal reflux, then more extensive investigation may be required. These tests are usually available only at a tertiary center and include 24-hour pH probe monitoring of the distal esophagus to quantify the frequency, duration and pattern (postprandial, nocturnal) of reflux episodes and their association with other events. A pH probe is best performed in conjunction with respiratory monitoring to determine whether respiratory symptoms such as apnea or wheezing coincide with reflux.

Esophageal manometry may be performed to exclude motor disorders of the esophagus such as achalasia, and nuclear medicine gastric emptying studies can document those children in whom delayed gastric emptying contributes to reflux. To determine if esophagitis is present, esophageal mucosal tissue may be obtained either by endoscopic or suction biopsy. Features of esophagitis on biopsy include esophageal inflammatory infiltrate (especially an increased number of eosinophils), increased thickness of the basal layer, increased papillary height and ulceration with a neutrophil infiltrate. Bronchoscopy and bronchial-alveolar lavage to look for lipid-laden macrophages may be of help in the diagnosis of reflux-related respiratory infection.

Management of most children with gastroesophageal reflux often requires no more than an explanation to parents that reflux is a normal phenomenon in infants. Conservative measures may be helpful. These include positioning the infant and smaller, more frequent thickened feedings; rarely, continuous drip feedings may be necessary. Positioning the child in a head-elevated prone position after feeds can be useful, but the use of infant seats has been shown to make reflux worse. Thickening of feeds (usually with rice formula) decreases the number of emeses and time crying, but has not been shown to decrease the time spent refluxing, as shown by esophageal pH monitoring.

For those children with complicated or severe reflux unresponsive to conservative management, drug therapy may be necessary. This usually entails the use of a prokinetic agent and/or an acid suppressant. Cisapride is the prokinetic agent of choice as it lacks the neurological and respiratory side effects of other prokinetic agents such as metoclopramide and bethanechol. Cisapride acts peripherally to increase the release of acetylcholine from the intestinal myenteric plexus and has been shown to be effective in the treatment of gastroesophageal reflux in children. It is given orally approximately 30 minutes prior to feedings at a dose of 0.2mg/kg/dose q.i.d. up to a maximal dose of 0.3 mg/kg/dose. It is well tolerated and side effects are generally limited to an increased stool frequency. However, recent reports have shown that cisapride can induce life-threatening ventricular arrhythmias in individuals with conduction abnormalities such as a prolonged Q-T interval; it should be used with extreme caution in such patients. Acid suppression is helpful in those patients with evidence of esophagitis or reflux-associated pain. An H₂ antagonist such as ranitidine or cimetidine is often sufficient for pain relief, but patients with esophagitis may require more powerful acid suppression with a proton pump inhibitor such as omeprazole to achieve healing.

Surgery may be necessary in patients with gastroesophageal reflux who fail medical therapy or who have life-threatening reflux-associated apnea. Nissen fundoplication, where the fundus of the stomach is wrapped 360º around the lower esophagus to produce an esophageal high-pressure zone, is the operation of choice. Fundoplication is effective, and a successful clinical outcome is seen in almost 90% of patients at five years, but major complications such as postoperative adhesions, wound infection and pneumonia occur in approximately 10-20% of patients. Fundoplication is less successful in controlling reflux in neurologically impaired children, where clinical success rates are of the order of 50-60% and complication rates are higher. Recently, newer surgical techniques such as partial wraps (<360º) and laparoscopic fundoplication have become available, but it is not yet known whether the long-term success rates or complications of these procedures differ from the open Nissen technique.