|Trào ngược dạ dày – thực quản ở trẻ nhỏ|
|Trào ngược dạ dày – thực quản (GOR) là tình trạng tống xuất sữa và các chất khác trong lòng dạ dày vào thực quản một cách dễ dàng (nôn trớ). Cần phải chẩn đoán phân biệt với tình trạng nôn với sự co thắt mạnh mẽ cơ hoành và các cơ thành bụng|
Gastro-oesophageal Reflux in Infancy
|Hemant Bhavsar, MBBS, DCH, MRCPCH; Mick Cullen, RSCN; R Mark Beattie, BSc, MBBS, MRCP, FRCPCH|
WHAT IS GASTRO-OESOPHAGEAL REFLUX?
Gastro-oesophageal reflux (GOR) is the non-forceful regurgitation of milk and other gastric contents into the oesophagus (regurgitation). It should be distinguished from vomiting which is an active process requiring the forceful contraction of the diaphragm and abdominal muscles. It is a normal physiological phenomenon, particularly common in infancy. It is also seen in older children and adults less frequently and only pathological when it occurs in excess.
More than 50% of normal infants regurgitate more than twice a day. Functional reflux is regurgitation without morbidity or clinical signs suggestive of gastro-oesophageal reflux disease (GORD).
Reflux is most common between 1 and 4 months. Major factors include the high fluid volume per kilogram ingested at that age compared with older children/adults, posture and the functional immaturity of the lower oesophageal sphincter. By 12–18 months, most symptomatic reflux will have resolved as the sphincter matures, the infant adopts an upright posture, and is established on a mixed rather than milk-predominant diet.
GASTRO-OESOPHAGEAL REFLUX DISEASE
Gastro-oesophageal reflux disease is defined as ‘gastro-oesophageal reflux associated with troublesome symptoms or complications’. It refers to reflux with significant morbidity including faltering growth, respiratory disease, and oesophagitis or complications of oesophagitis such as stricture. Therefore, within the umbrella termgastro-oesophageal reflux, there is a considerable spectrum with a range of severity from an intermittent nuisance to a life-threatening disease.
Most children with GORD will present in the first year, but there are some who present later with symptoms including heartburn, acid regurgitation, and dysphagia.
Severe GOR can cause oesophagitis. Oesophagitis implies acid or, rarely, alkali-induced damage to the lower oesophagus. Intake of food by mouth stimulates gastric acid secretion. Reflux of this acid in the lower oesophagus can be painful. GORD is the most common cause of oesophagitis in children.
Crying and irritability may be symptoms of oesophagitis in infants, similar to adults’ complaint of heartburn and chest pain. Children with oesophagitis can develop food aversion as a consequence of experiencing pain when they eat, and food refusal can be the presenting feature. This is likely to be a significant factor in the faltering growth seen in some children with reflux. This can be difficult to diagnose and requires treatment of oesophagitis before dealing with feeding issues.
SYMPTOMS OF GORD
GORD can be oesophageal or extra-oesophageal depending on the presenting symptoms.
1. Symptoms purported to be due to GORD
2. Symptomatic syndrome
3. Syndromes with oesophageal injury
1. Definite association
Risk factors for GORD include obesity, neurologic impairment, repaired oesophageal atresia or other congenital oesophageal disease, cystic fibrosis, hiatus hernia, repaired achalasia, lung transplantation, and a family history of GORD.
DIFFERENTIAL DIAGNOSIS OF GORD
APPROACH TO THE MANAGEMENT OF GOR
1. Physiological reflux is common in infancy and is a clinical diagnosis. For most parents, reassurance that the condition will resolve without treatment is all that is needed. It is important to consider the differential diagnosis.
2. Full assessment of infants is essential, including a full feeding history, to explore the possibility of overfeeding or difficulty with feeding. Careful attention needs to be paid to severity of symptoms, faltering growth and relevant social factors, eg, parental anxiety and stress (Table 1).
3. Severe cases need further assessments and investigation. These include barium study, pH study, impedance study, milk scan, oesophagoscopy, and oesophageal biopsy (described below).
4. There is a step-up approach to management.
5. Difficult cases require assessment by a multidisciplinary team including dietitian, speech and language therapist, paediatric gastroenterologist and paediatric surgeon.
INDICATIONS FOR INVESTIGATION OF PRESUMED GOR
HOW TO INVESTIGATE GOR?
Barium swallow assesses the patient over only a short period and can therefore either miss pathological reflux or overdiagnose physiological reflux. It is however an important test to rule out large hiatus hernia, oesophageal stricture or web, atypical pyloric stenosis, gastric web, duodenal web, malrotation, volvulus, or other anatomical causes of recurrent vomiting.
This is considered by many to be the gold standard investigation test for acid reflux. It is a valid quantitative measure of oesophageal acid exposure, with established normal ranges.
Specific Indications for pH Study
Physiological Basis and Technique of Using pH Probe
Acid reflux into the oesophagus occurs in all infants as a physiological phenomenon and is only significant when it occurs in excess. The pH probe is designed to measure acidity (ie, acid reflux) in the lower oesophagus. The test relies on the infant/child being off anti-reflux therapy in the 48–72-hour period running up to the test.
The pH probe is a microelectrode passed through the nose and down the back of the throat to sit above the lower oesophageal sphincter. An acid reflux episode is defined as an oesophageal pH of < 4 for a specified minimum duration, usually 15–30 seconds. A set period, usually 24 hours, is recorded, with a note made of the number of episodes, frequency of episodes, and the relationship of reflux to eating, position, sleeping or activity, and especially symptoms. The most sensitive marker of acid reflux on pH study is the reflux index, defined as the percentage of time that oesophageal pH is < 4. This has been validated in several studies. pH study reports are shown in Figures 1 and 2.
Limitations of the Test
There are several limitations to pH studies, as follows:
The pH study may be falsely negative in the presence of alkaline reflux (reflux of alkaline stomach contents, eg, during continuous feeding/duodenal contents). Either dual pH monitoring (electrode in stomach and oesophagus), oesophageal impedance or a radio-labelled milk scan is required to detect this.
This uses continuous evaluation for up to an hour after radio-labelled meal. It is independent of pH so it can detect alkaline reflux. It is performed over a period of up to an hour with a delayed 24-hour film to look for aspiration. The technique is useful for diagnosis of non-acid reflux. It also gives an assessment of gastric emptying which is a useful indicator of overall gut motility. Markedly delayed gastric emptying is common in children with cerebral palsy in whom vomiting may reflect an overall gut dysmotility rather than GORD. Sensitivity for detection of reflux is variable but can approach 95%.
This measures the changes in the electrical impedance (resistance) between multiple electrodes located along an oesophageal catheter. Oesophageal impedance tracings are then analysed for the typical changes caused by liquid, solid, air or mixed bolus. The impedance changes suggestive of retrograde bolus movement indicate reflux. This test is superior to pH monitoring alone for the evaluation of the temporal relation between symptoms and GOR.
This measures the pressure inside the lower part of the oesophagus. It may be abnormal in patients with GORD, but the findings are not sufficiently sensitive or specific to confirm the diagnosis, nor to predict response to medical or surgical therapy. It is useful to confirm a diagnosis of achalasia or other motor disorders of the oesophagus that may mimic GORD.
OESOPHAGOSCOPY AND OESOPHAGEAL BIOPSY
In children with suspected oesophagitis, upper gastrointestinal endoscopy is a useful investigation and should be considered in all children with severe symptomatic reflux. Biopsies need to be taken, as significant histological abnormality may not be obvious endoscopically. An eosinophilic infiltrate is a characteristic of reflux oesophagitis. However, an excess of eosinophils suggests cow’s milk allergic oesophagitis/EO.
Normal oesophageal histology does not exclude GOR.
In children with documented oesophagitis and normal pH study, other diagnoses should be considered.
NON-REFLUX CAUSES OF OESOPHAGITIS
TREATMENT OF GOR
Most patients with physiological gastro-oesophageal reflux are managed in primary care by the health visitor and general practitioner.
Simple measures are often effective, including:
Drug treatment is indicated in children with severe symptomatic reflux or signs and symptoms suggestive of GORD.
The major pharmacological agents currently used for treating GORD in children are gastric acid–buffering agents, mucosal surface barriers, and gastric anti-secretory agents. Acid suppressant agents are the mainstay of treatment for all but patients with occasional symptoms. The potential adverse effects of acid suppression, including increased risk of community-acquired pneumonias and gastrointestinal infections, need to be balanced against the benefits of therapy.
STEP-UP APPROACH TO MEDICAL TREATMENT OF GOR
Step 1 – lifestyle changes
Compound alginates are effective symptomatic treatment for GOR. Infant aluminum hydroxide/magnesium trisilicate works by reacting with gastric acid to form a viscous gel. It comes in a dual sachet and each half is a dose. One dose for under 4.5 kg and two doses for over 4.5 kg are given for a maximum of six times a day. In infants, aluminium hydroxide/magnesium trisilicate can be added to feed or, for breast-fed infants, dissolved in cooled boiled water and given by spoon after a feed. Chronic use of alginates is not recommended for GORD because some have absorbable components that may have adverse effects with long-term use.
Acid Suppression Agents
Histamine H2 receptor blockers are widely used in the management of reflux. They are safe and well tolerated and can be considered before any further investigation in children who are thriving and in whom the diagnosis is robust. Ranitidine is the most commonly used H2 receptor blocker. Oral ranitidine provides symptomatic relief and endoscopic improvement of oesophagitis in children with GORD. Dose is 2–4 mg/kg twice daily; the syrup can be used (75 mg/5 mL).
Proton pump inhibitors (eg, omeprazole, lanzoprasole) increase the pH of gastric content, decrease the total volume of secretions, and facilitate emptying. For healing of erosive oesophagitis and relief of symptoms, PPIs are superior to histamine receptor blockers. Omeprazole is the most commonly used PPI and is shown to be effective in children with GORD resistant to ranitidine. It is available as dispersible tablets or capsules given once daily. The tablet can be gently mixed or dispersed (not crushed), or the capsule can be broken for ease of administration in children. Dosage is 0.7–1.4 mg/kg per day although higher doses can be used, at up to 3 mg/kg. In practice, twice daily doses are often used. Lanzoprazole is available as dispersible tablets and given in the dose of 0.5–1 mg/kg once daily.
These drugs increase lower oesophageal spincture pressure, improve oesophageal clearance, and promote gastric emptying. Efficacy data are limited. Examples include metoclopramide, domperidone, cisapride and erythromycin. Cisapride has been withdrawn from use because of concerns about cardiotoxicity. Although the effectiveness of domperidone in children is unproven, it is often used with no serious adverse effects at 0.3–0.6 mg/kg three times daily in children. It can occasionally exacerbate reflux.
Buffering agents (magnesium hydroxide and aluminium hydroxide) and sucralfate are useful for occasional heartburn. Buffering agents carry significant risk of toxicity and are not recommended for long-term use. Sucralfate binds to inflamed mucosa and forms a protective layer that resists further damage from gastric acid.
CHILDREN WITH SEVERE REFLUX RESISTANT TO MEDICAL MANAGEMENT MAY BENEFIT FROM:
Surgery is usually fundoplication with consideration of a pyloroplasty if there is delayed gastric emptying. A gastrostomy for feeding is often done at the same time, particularly if there are feeding problems, eg, neurodisability.
Most fundoplications are now done laparoscopically with good results in terms of reduced post-operative complications, reduced stay in hospital, and long-term outcome.
Children with underlying disorders predisposing to the most severe GORD are at the highest risk for operative morbidity and post-operative failure. Before surgery, it is essential to rule out non-GORD causes of symptoms and ensure that the diagnosis of chronic-relapsing GORD is firmly established. It is important to provide families with appropriate education and a realistic understanding of the potential complications of surgery, which include recurrence of reflux (10%), retching, bloating, dumping, and intestinal obstruction.
Patient Groups at High Risk of Needing Surgery
GOR and Neurodisability
Children with cerebral palsy commonly suffer from feeding difficulties of which GOR is a component. Assessment of the contribution of GOR requires careful assessment.
There are many potential causes of feeding difficulties in children with neurodisability:
Children require careful multidisciplinary assessment by a feeding team including dietitian, speech and language therapist, occupational therapist, and the neurodevelopmental paediatrician. A video barium assessment of the swallow is often indicated. GORD, if present, should be treated aggressively.
Attention to nutrition is of key importance, and many children with feeding difficulties benefit from a feeding gastrostomy. A fundoplication is required if reflux is severe, although in some cases, improved nutritional status will result in improvement of the reflux.
The motility of the gut is a key factor in feed tolerance in children with cerebral palsy who may have delayed gastric emptying which impact significantly on the ability to feed, particularly if nutrition is dependent upon nasogastric or gastrostomy feeding. It is important to recognize this as a separate condition from reflux. Abdominal pain, bloating and constipation are common features of gut dysmotility. Therapeutic strategies include explanation and reassurance, prokinetic agent such as domperidone, laxatives and, occasionally (if there is a need for distal gut deflation), suppositories. It may be necessary to give feeds by continuous infusion. It may also be necessary to consider gastro-jejunal feeding. A milk-free diet for a trial period of 2–4 weeks can be helpful. Hydrolysed protein formula feeds may be given as a milk substitute.
GOR and Respiratory Disease
GOR has been associated with significant symptoms in infants and children. There is a complex relationship between asthma and GOR, manifested by a bidirectional cause and effect.
One postulated mechanism for GOR-mediated airway disease involves micro-aspiration of gastric contents that leads to inflammation and broncho- spasm. However, experimental evidence also supports the involvement of oesophageal acid–induced reflex bronchospasm, in the absence of frank aspiration. In such cases, GOR therapy using either H2 blockers or PPIs has been shown to benefit patients with steroid-dependent asthma, nocturnal cough, and reflux symptoms. Similarly, intrinsic lung disease may, through excessive coughing, result in reflux.
The association between GOR and apparent life-threatening events is somewhat controversial and probably only relevant if the infant vomits, chokes or turns blue during or immediately after feeds.
In infants and young children, EO presents with symptoms similar to those of GORD but fails to respond to conventional acid blockade therapy. In older children, dysphagia and food impaction can occur.
EO is often seen in patients with atopy who have asthma, eczema or chronic rhinitis, or in those with family history of atopic disease. Multiple food antigens can also induce EO.
Endoscopy may reveal a ringed appearance or linear furrows. Standard biopsy findings reveal severe eosinophilic infiltration; more than 15–20 eosinophils per high-magnification microscopic field are necessary for diagnosis. In contrast to GORD, EO involves the mucosa, submucosa and, possibly, the muscularis.
EO is currently diagnosed based solely on endoscopic findings. Standardized skin prick testing and radioallergosorbent testing are not useful in the diagnosis of EO. About two-thirds of children with EO have an increased peripheral eosinophilic count. The exact pathophysiology of EO is unknown, but contact of the allergen with the oesophageal or intestinal mucosa is thought to be the initiating event.
Treatments include those for GOR, trial of dietary elimination, inhaled (swallowed) or oral steroids, anti-inflammatories, and immunosuppression. There is a natural history of relapse, remission and chronicity.
CASE STUDY 1
A 5-week-old, term, breast-fed baby presented unsettled in the evenings and at night. She was vomiting (not the whole feed), with episodes of arching. She has continued to gain weight appropriately. Mum was given advice on positioning and feeding, along with explanation and reassurance about the natural history of GOR. The symptoms, however, continued and infant aluminium hydroxide/magnesium trisilicate was started. She continued to thrive. Her reflux gradually improved with time. This infant presumably had functional GOR. There may have been a component of ‘infantile colic’. Infantile colic is poorly understood but, like reflux, generally improves. Symptoms may overlap and can cause considerable anxiety to parents.
CASE STUDY 2
A 3-month-old exclusively breast-fed baby was started on formula milk. He developed symptoms of retching (distress) with most feeds, constipation, and milk refusal. His symptoms failed to improve with anti-reflux therapy and he lost weight. Cow’s milk allergy was considered. He was referred to a specialist clinic where he was started on extensively hydrolysed formula. Weaning was delayed to 6 months, after which he was started on dairy- free weaning solids, with dietetic support. His symptoms improved rapidly and he showed good catch-up growth. Cow’s milk was gradually introduced in his diet from the age of 12 months, after a day case challenge, which he tolerated well. His diet was subsequently normalized. Cow’s milk allergy is the commonest food allergy in infancy and usually resolves by 2 years of life and almost always by 5 years of age. GOR can coexist, but poor response to anti-reflux therapy should prompt consideration of cow’s milk allergy.
CASE STUDY 3
A 2-year-old boy with spastic quadriplegia and intractable epilepsy presented to hospital repeatedly with aspiration pneumonia and poor weight gain. He was nasogastrically fed at home, and parents reported frequent retching and vomiting associated with feeds in spite of being on ranitidine and domperidone. His pH study confirmed severe reflux. He failed to respond to PPIs at good doses and trial of hydrolysed formula feed. He underwent fundoplication with feeding gastrostomy. Post-operatively, his admissions to hospital were reduced. Parents reported good weight gain and improved feed tolerance.
CASE STUDY 4
A 15-month-old baby presented with history of poor weight gain, recurrent vomiting and food refusal from very early age. She was born at term and there was no significant antenatal or medical history. She was particularly distressed at meal times as if she was in pain. Further investigations revealed significant reflux (reflux index 14%) and endoscopic findings of oesophagitis. She was treated with PPIs, with improvement in her symptoms. Her symptoms were secondary to acid reflux in response to gastric acid secretion associated with meal times. Her feeding improved with reflux treatment.
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© 2011 Elsevier Ltd. Initially published in Paediatrics and Child Health 2011;21(9):394–400.
About the Authors
Hemant Bhavsar is a Speciality Registrar in Paediatric Gastroenterology in the Paediatric Medical unit at Southampton General Hospital, Tremona Road, Southampton, UK. Mick Cullen is a Paediatric Gastroenterology Nurse Specialist in the Paediatric Medical unit at Southampton General Hospital, Tremona Road, Southampton, UK. R Mark Beattie is Consultant Paediatric Gastroenterologist in the Paediatric Medical unit at Southampton General Hospital, Tremona Road, Southampton, UK.