Gastro-esophageal reflux disease
Gastro-esophageal reflux (GER) is the passage of gastric contents into the esophagus, with or without regurgitation and vomiting. North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition (NASPGHAN) and ESPGHAN defined pediatric gastro-esophageal reflux disease (GERD) as GER leads to troublesome symptoms which affect daily functioning and/or complications, such as hematemesis, dysphagia, erosive esophagitis, poor weight gain, feeding refusal, dystonic neck posturing, apnea, recurrent aspiration pneumonia, coughing or choking at the end of feeding in infants and children. The children who had specific underlying conditions such as neurolgical disease, pulmonary disease (e.g., cystic fibrosis), congenital gastrointestinal abnormalities (e.g.,diaphragmatic hernia, esophageal atresia, intestinal atresia.), obesity or prematurity are more vulnerable for GERD34. Lower esophageal sphincter (LES), angle of His (angle between the esophagus and the gastric fundus), the crural diaphgram and phrenoesophageal ligament are the components of the anti-reflux barrier. The LES relaxes during swallowing and allows the pass of esophageal contents to the stomach. The postprandial gastric distension triggers transient LES relaxations (TLESRs) and the gastric contents move upward into the esophagus. Despite TLESRs are considered to be the major cause of GER episodes, delayed gastric emptying, decreased LES pressure, increase in the His angle, increased intraabdominal pressure may lead GER. Coughing, straining, increased respiratory effort, medications, obesity, lying on right side position may cause GER due to anti-reflux barrier impairement35-38.
In the study of mechanical ventilated critically ill patients, the basal LES pressure was found to be low and a minimal increase in abdominal pressure due to such as suctioning, straining, coughing may cause frequent reflux episodes. Also medications like anti-cholinergic drugs, calcium canal blockers, barbiturates may relax LES39. Enteral nutrition related gastric distension or delayed gastric emptying may increase the frequency of TLESRs and causes increased GER episodes in these patients31. Newton M et al40. reported that GERD was diagnosed in 20% of the children with tracheostomy and of these children 12.4% had tracheostomy related complications, with odds ratio of 1.5 for developing tracheostomy related complications. Ertuğrul A et al41. demonstrated GERD was the major co-morbidity (%28) in children dependent HIMV, most of them had an underlying a neuromuscular disease. In the study of Blanchi ET et al.42, the prevalence of reflux in the adults with tracheostomy was reported as 45.2% and there was no typical symptoms most of 24-hour pHmetry and manometry measurement.
In the presence of the GERD related symptoms in infants and children with MV, red flag symptom and signs should be investigated (Table 6). In the presence of these findings the appropriate tests and radiologic evaluation should be performed to rule out other pathological conditions (Table 7)34-38.
The treatment of GERD in otherwise healthy infants and children were detailed in ESPGHAN and NASPGHAN recommendations34. In suspicion of GERD and if there is no red flag symptom and/or signs, the first step in treatment should be feeding modification. The head elevation and positioning is not recommended in sleeping infants due to the risk of sudden infant death syndrome34, but there is no clear data for the infants with tracheostomy.
The nutritional interventions should be made according to patients underlying illness, concomitant symptoms or disorders, age and nutritional status. Food thickeners may be given to orally feeding patients. Reducing feeding volumes, increasing feeding frequency and avoiding overfeeding may relief the symptoms. If the infant fails to these modifications, an extensively hydrolyzed protein-based formula and in breastfed infants elimination of cow’s milk from maternal diet should be considered for 2- to 4-weeks. If there is no response to extensively hydrolyzed protein based formula, an amino-acid based formula may be given. In children with NI who fed with tube whey based formula may be given, it also help to gastric emptying. If there is no improvement, acid suppression treatment should be considered for 4-8 weeks. The use of alginates may slightly improve the GERD symptoms and signs but ESPGHAN and NASPGHAN do not recommend use antacids/alginates for chronic treatment of infants and children with GERD. Also proton pump inhibitors (PPIs) may be considered in the treatment. If the symptoms improve in 4-8 weeks period, PPIs can be ceased6,34-38.
If there is no response to the optimal medical treatment in 4-8 weeks (refractory GERD) or weaning attempts of PPIs are failed within 6-12 months period, possible underlying conditions which may lead to GERD symptoms and efficacy of treatment (e.g., drug usage, dosage, adherence, interactions) should be evaluated.
In suspect of congenital gastrointestinal abnormalities such as hiatal hernia, pyloric stenosis, malrotation, duodenal or antral web, duodenal or esophageal stenosis, or esophageal stricture, achalasia, extrinsic compression of esophagus barium/water soluble radiopaque swallowing follow-through studies should be performed. Abdominal ultrasound also may be helpful to detect the congenital abnormalities. Follow-through studies and abdominal ultrasound is not recommended to diagnose GERD34-38.
In the suspicion of GERD due to persistent troublesome symptoms, the association of the symptoms and gastroesophageal reflux events (both acid and non-acid) should be identified by pH-multichannel intra-luminal impedance (MII). If it is not available only pH-metry can demonstrate the relation of symptoms only with acid GER events.
Esophagogastroduodenoscopy with biopsies should be performed to clarify the etiology of esophagitis (ie, eosinophilic esophagitis) or identify a mucosal disease as a complication of the GERD such as erosive esophagitis and Barrett esophagitis34-38.
In the presence of reflux-related erosive esophagitis in infants and children, the first-line treatment is proton pump inhibitors (PPIs). If PPIs are not available histamine-2 receptor antagonists (H2RAs) may be used. Baclofen may be considered before surgery in refractory GERD. Kawai et al43. reported a decrease in vomiting, number of acid refluxes with the gamma-aminobutyric acid type B receptor agonist baclofen. The use of domperidon, metoclopramide or any other prokinetics (e.g.,,erythromycin) in infants and children with GERD is not recommended34.
Since the incidence of GERD in neurologically impaired children is high (up to 70%) for these clinically fragile patients, ESPGHAN recommended using whey-based formulas, thickening the enteral formulas, and PPIs treatment before diagnostic tests.. Despite GERD symptoms cannot be expressed by severely neurologically impaired patients, objective diagnostic tests such as esophageal pH-metry or pH/multichannel intraluminal impedance monitoring, and/or upper GI endoscopy will be benefical to determine the futher need of PPIs treatment6,34.
In the treatment of infants and children with GERD who are refractory to optimal medical treatment, transpyloric or jejunal feedings may be an alternative treatment to fundoplication, but there is no strong evidence. In neurologically impaired children both procedures didn’t prevent aspiration pneumonia. This condition may be independent of the reflux events and related to their swallowing dysfunction34,44. The complication rates of transpyloric or jejunal feeding reported to be considerably high about 85%; including clogging, dislodgement, intussusception, and perforation45,46.
Anti-reflux surgery is recommended as foloows; life threatening complication under optimal medical treatment, refractory GERD symptoms, underlying a chronic condition (e.g.,neurologically impaired, cystic fibrosis), need for chronic pharmacotherapy to control the signs and/or symptoms of GERD. Fundoplication leads to decrease the baseline pressure of LES, the number of TLESRs and increase the length of intra-abdominal esophagus. Despite different anti-reflux surgical procedures, Nissen fundoplication is accepted as gold standart technique, with shorter hospital stay and low incidence of perioperative complications and also morbidity. Unfortunately, no reduction of extraesophageal symptoms such as pneumonia and mechanical ventilation requirement was demonstrated in neurological impaired children after fundiplication44,47,48. Also, more than 75% of the patients couldn’t cease acid suppression medications for at least one year after fundoplication49. After fundoplication gas-bloat, early satiety or pain after feeding, dysphagia, retching, worsening aspiration risk from esophageal stasis, unwrapping and redo fundoplication (2.2%-12.2%) are the other reported side effects50,51.
Total esophagogastric disconnection may be considered as a rescue procedure for neurologically impaired children with a failed fundoplication Since these complications may inversly effect the patients with tracheostomy, the parents should be carefully informed for the risks and benefits of the surgical interventions34.