Gastroesophageal reflux in children

Transcription

1 Gastroesophageal reflux in children 浙江大学医学院附属儿童医院 江米足

2 Definition of GER or GERD GER: means involuntary passage of gastric contents into the esophagus and is often physiological. GERD: means symptoms or complications associated with pathological GER. Hassall E. Arch Dis Child 2005

3 Prevalence USA: 3-9 y:566 cases, 1.8% y:615 cases, 3.5% Adults (>18 y):22% The prevalence of GERD slowly increases with age during childhood and becomes quite frequent among young adults. Nelson SP, et al. Arch Pediatr Adolesc Med 2000

4 Prevalence Australia:863 infants 3-4m(41%) 13-14m(<5%) India:602 infants 1-6m(55%) 7-12m(15%) 12-24m(10%) Italy:2642 infants 0-12m (12%) Martin AJ, et al. Pediatrics 2002 Campanozzi A et al. Pediatrics 2009 De S, et al. Trop Gastroenterol 2001

5 Prevalence GER is frequently seen in early infancy and it almost disappears by one year of age. Persistence or appearance of regurgitation beyond 18 months of age is suggestive of pathological condition. The prevalence of GERD in infancy is 5%-9% of all infants with regurgitation. Poddar U. Indian Pediatr 2013

6 Anti-reflux mechanism Liu XL, et al. Hong Kong Med J 2012

7 Closing mechanisms The diaphragm creates a pinch cork action and functions to increase the pressure The intra-abdominal portion of the esophagus The angle of His between the stomach and the esophagus Opening mechanisms Increased intra-abdominal pressure (from abdominal tumours, coughing, and constipation) increases intra-gastric pressure Liu XL, et al. Hong Kong Med J 2012

8 Risk factors of GER Poor function of LES (pressure and length) Esophageal dysmotility resulting in reduced clearance Abnormal anatomy-including congenital malformation (short intra-abdominal esophagus) or acquired disease (esophageal atresia repair) Higher intra-gastric pressure and delayed gastric emptying Liu XL, et al. Hong Kong Med J 2012

9 Transient lower esophageal sphincter relaxations (TLESR) TLESR is defined as an abrupt decrease in LES pressure to the level of the intra-gastric pressure unrelated to swallowing, with a relatively longer duration (8-10 s) than seen with relaxations triggered by a swallow GER cc TLESR Omari TI, et al. Gut 2002

10 TLESR TLESR is the predominant mechanism of GER triggering, accounting for % (median 91.5%) of all GER episodes. Omari TI, et al. Gut 2002

11 Clinical symptoms of GER Clinical features of GER vary in children of different ages. Typical symptoms Regurgitation Vomiting Heartburn Chest pain Atypical symptoms Feeding difficulties/anorexia Failure to thrive Postural defect Stridor Chronic cough Laryngitis, otitis Asthma sinusitis Martigne L, et al. Eur J Pediatr 2012

12 Yuksel ES, et al. Eur J Med Sci 2010

13 Laryngeal findings in reflux laryngitis Kamal A, et al. Best Practice Res Clin Gastroenterol 2010

14 Presenting symptoms Regurgitation or vomiting Healthy: no failure to thrive or other associated symptoms Infants with GERD Growth failure or indirect symptoms of pain due to esophagitis like irritability, feeding difficulty, sleeping difficulties, crying episodes, anemia Rarely apnea or ALTE Chronic respiratory diseases and upper airway problems like sinusitis, otitis media, laryngitis, dental erosion In children and adolescents, symptoms and complications of GERD are heartburn or substernal pain

15 Presenting symptoms of GERD Infants Vomiting Poor weight gain Children Regurgitation Anemia and hematemesis Irritability Feeding refusal or dysphagia Dysphagia Heartburn and retrosternal chest pain Recurrent pneumonia Asthma and upper airway symptoms Apnea or apparent lifethreatening event (ALTE) Recurrent pneumonia Asthma or chronic cough Michail S. Pediatr Review 2007

16 Diagnostic test Esophageal ph monitoring Multichannel intraluminal impedance (MII) measurement High resolution manometry (HRM) Endoscopy Confocal laser endomicroscopy Barium UGI series Nuclear scintigraphy GER questionnaire Rome III criteria

17 Esophageal ph monitoring To establish the presence of acidic reflux (ph<4) To quantify reflux in patients with mainly extra-esophageal symptoms To assess the efficacy of medical therapy To measure GER in patients not responding to antireflux treatment and in research

18 24 hr ambularoty ph-metry

19 Parameters of ph monitoring Percent total time with a ph<4.0 (reflux index, RI) Percent upright time with a ph<4.0 Percent supine time with a ph<4.0 Number of reflux episodes Number of reflux episodes lasting 5 min Longest reflux episode (min) The scoring system Boix-Ochoa score Demeester score

20 Esophageal ph monitoring Advantages Be done in any age Be relatively non-invasive Disadvantage Does not measure non-acid or weakly acidic reflux

21 Multichannel intraluminalimpedance (MII) measurement To detect the change in electrical resistance (or impedance) when substances pass through the esophagus using a series of impedance sensors lying 1 cm apart on a probe Impedance is inversely proportional to electrical conductivity Since the conductivity of liquid (high) and air (low) is different, MII can easily differentiate liquid from gas reflux

22 The basic principle of impedance measurement Inversely proportional to conductivity of luminal contents Low conductivity = High Ω Air Food High conductivity = Low Ω Saliva Refluxate 2000 Ω 0 z

23 van Wijk MP, et al. J Pediatr Gastroenterol Nutr 2009

24 MII-pH monitoring (acid) Z Z Z Z Z Z ph Z Z Z Z Z TLESR Z 4 ph 8 volume clearance 4 ph Acid GER 3 10 Acid Clearance 10sec

25 MII-pH monitoring (non-acid) Z1 Z2 Z3 ph Z4 Z5 ph 4 9 volume clearance 10sec

26 Wenzl TG, et al. J Pediatr Gastroenterol Nutr 2012

27 Wenzl TG, et al. J Pediatr Gastroenterol Nutr 2012

28 Advantages of MII-pH monitoring Be superior to ph-study alone for evaluation of GER-related symptom association Picking up acid, non-acid or weakly acid reflux, the direction of reflux To distinguish between liquid, solid and gas reflux in all age groups

29 Limitations of MII-pH study High cost Limited availability Limited therapeutic implications (clinical relevance of measuring non-acidic reflux remains doubtful) The lack of evidence-based parameters for assessment of GER

30 High resolution manometry (HRM) Conventional manometry assemblies detect pressure using a catheter with several waterperfused sideholes by gaps between the pressure sensors which are several centimeters long. HRM catheters are equipped with intraluminal pressure transducers Simultaneously measure from hypopharynx to stomach Assign color to specific pressure levels which are than presented in a spatiotemporal plot Pressure topography plots are more intuitive and easier learned by clinicians Kessing BF, et al. Curr Gastroenterol Rep 2012

31 Esophageal HRM and manometry 水平为时间轴, 左纵轴压力色彩带 ( 颜色越暖, 压力越高 ), 右纵轴为食管位置 ),TZ 为移行区

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34 achalasia

35 Clinical application of HRM HRM is superior to other diagnostic tools for the evaluation of achalasia and contributes to a more specific classification of esophageal disorders in patients with non-obstructive dysphagia Kessing BF, et al. Curr Gastroenterol Rep 2012

36 Endoscopy Upper gastrointestinal endoscopy is the best method of detecting esophagitis as a consequence of GERD. Normal endoscopy (found in 60%-80% cases of GERD in children) does not rule out GERD and this type of GERD is called Non-erosive reflux disease (NERD). Endoscopy needs to be combined with a biopsy to increase the diagnostic yield (especially in NERD) and to rule out other causes of esophagitis (like eosinophilic esophagitis, Crohn s disease).

37 Indications of endoscopy Persistence of symptoms despite therapy Dysphagia or odynophagia Evidence of GI bleeding or iron deficiency anemia Stricture or ulcer on barium study Long duration GERD to detect Barrett s esophagus.

38 Advantages of endoscopy Gives a direct information about the presence and severity of esophagitis Detects complications like ulcer, stricture, Barrett s esophagus Documents healing of erosive esophagitis after therapy. Exclude other causes of esophagitis by endoscopic esophageal biopsy.

39 Los Angeles classification A One or more mucosal breaks, each 5 mm in length B At least one mucosal break > 5 mm long, but not continuous between the tops of adjacent mucosal folds C At least one mucosal break that is continuous between the tops of adjacent mucosal folds, but which is not circumferential (< 75% of luminal circumference) D Mucosal break that involves at least 75% of the luminal circumference

40 Kamal A, et al. Best Practice Res Clin Gastroenterol 2010

41 The evidence of histology Histology is more sensitive than endoscopy in the early stage (non-erosive stage). Erosive esophagitis is the most definite evidence of GERD on endoscopy. Biopsy (2 cm proximal to gastroesophageal junction) helps to establish the diagnosis of GERD if there is no erosion or mucosal break on endoscopy.

42 Esophageal histological features of GERD Basal zone hyperplasia (>20% of total thickness) Elongation of papillae (>50% of total thickness) Infiltration with neutrophils or eosinophils (<15/high power field) The presence of dilated intercellular spaces Growing of blood vessels in papilla Histological changes are neither sensitive nor specific for reflux disease in NERD cases and should not be used alone to diagnose or exclude GERD Poddar U. Indian Pediatr 2013 Tobey NA, et al. Gastroenterology 1996 Boccia G, et al. Am J Gastroenterol 2007 Vandenplas Y, et al. J Pediatr Gastroenterol Nutr 2009

43 Barium UGI series Be useful to detect anatomical anomalies such as the angle of His, esophageal dysmotility, mucosal irregularity, stricture, and hiatus hernia, but not useful in diagnosing GERD. The sensitivity and specificity to diagnose GERD is less than 50%. Cannot differentiate physiological from pathological reflux. Most useful in ruling out underlying obstruction such as that due to achalasia

44 Nuclear scintigraphy Be a non-invasive test but has poor sensitivity and specificity. To confirm silent aspiration in patients with recurrent pneumonia due to aspiration of gastric contents. Be a useful tool in evaluation of delayed gastric emptying Not recommended for the routine evaluation of pediatric patients with suspected GERD.

45 Infant GER questionnaire (I-GERQ) Orenstein SR, et al. Clin Pediatr 1996

46 I-GERQ Maximum total score:25 Score>7, for diagnosing GERD in infants Sensitivity 74% Specificity 94% Can be used to segregate those infants who needs empirical therapy or further investigation because of its simplicity (take just 20 minutes to complete) and reproducibility.

47 Rome III criteria Must include all of the following in otherwise healthy infants 3 weeks to 12 months of age Regurgitation 2 or more times per day for 3 or more weeks No retching, hematemesis, aspiration, apnea, failure to thrive, feeding or swallowing difficulties, or abnormal posturing

48 Diagnostic test When symptoms are not classical and in cases with complicated GERD Endoscopy,pH study, barium upper GI series In a patient with classical symptoms of GERD No need to confirm the presence of GER by ph study or by endoscopy In patients with extra-esophageal symptoms like respiratory symptoms without any GER symptoms ph study is required to document reflux When esophagitis is suspected (pain or blood loss) Upper gastrointestinal endoscopy with esophageal biopsy is recommended Any suggestion of an anatomical abnormality like intestinal obstruction or dysphagia Barium upper GI series is indicated

49 Diagnostic approach to GERD There is no gold standard for the diagnosis of GERD. The choice of investigation depends on the clinical situation for which the investigation is asked for.

50 Diagnostic criteria of pathological GER RI is the main parameter in diagnosing GERD. RI 10%(<1 year), 5% (>1 year ) RI 10%(<1 year), 4.2%(>1 year) USA: RI 12% (<1 year), 6% (>1 year) RI>7% as abnormal, <3% as normal, 3-7% as indeterminate (ESPGHN, NASPGHN) Boix-Ochoa score >11.99 Demeester score >14.72 Van der Pol RJ, et al. J Pediatrics 2012 Vandenplas Y, et al. J Pediatr Gastroenterol Nutr 2009 Mattioli G, et al. Dig Dis Sci 2006 Aggarwal S, et al.trop Gastroenterol 2004 Wenzl TG. J Pediatr Gastroenterol Nutr 2011

51 Management---GER in infants Counseling-the most important part Explain the natural history of GER in infants to parents or care-givers Other measures Feeding advice Avoid overfeeding, forceful feeding Try to give small but frequent feeds positioning Prone position-not recommended (the risk of SIDS) Left lateral position (age>13m)-the best in preventing reflux feed thickening Adding rice, corn or potato starch decrease the number regurgitation of vomiting does not decreases the acid exposure of esophagus Feed thickener has only cosmetic value but no therapeutic benefit.

52 PPIs PPIs are not recommended in this subset of patient Only a few of the infants are likely to have acid-related cause for their symptoms The largest randomized, controlled trial in infants showed that for symptoms, presumably to be related to reflux disease, a PPI was not better than placebo. Orenstein SR, et al. J Pediatr 2009

53 Management---GERD in children Besides medication, life-style modification in terms of weight reduction, avoiding caffeine, chocolate, abstinence from alcohol, tobacco helps in children. Adolescents, like in adults, may benefit from the left lateral decubitus sleeping position with head-end elevation

54 Pharmacological therapy Acid suppressants Histamin-2 receptor antagonists (H2RA) Ranitidine: 6-8mg/kg/day, bid or tid Famotidine:1mg/kg/day, bid Proton pump inhibitors (PPIs) Omeprazole:0.7 to 3.5 mg/kg/day, qd Neutralizing or surface protective agents (antacids or sucralfate) Prokinetics

55 H 2 RA Rapid onset of action (in 30 min) Short acting (6 hr) acid suppressants used for on-demand therapy (SOS therapy) A lack of post-prandial acid suppressant effect Develop tachyphylaxis on long-term use (in 6 weeks) Cannot be used for long term therapy H 2 RA are less effective than PPI

56 PPIs Inhibit acid secretion by irreversibly blocking Na + -K + -ATPase in the apical membrane of parietal cells Be taken 30 min before breakfast as parietal cells get activated in response to a meal. Require a higher per kilogram dose than adults to obtain a similar degree of acid suppression due to higher metabolism of the drug. Omeprazole, 2-2.5mg/kg/day Lansoprazole, 1.4mg/kg/day

57 The advantages of PPIs More effective in relieving symptoms and healing esophagitis than any other acid suppressants Prolonged action (requires once daily dose) No tachyphylaxis on prolonged use Relatively safe drug on long term use Facilitate gastric emptying due to decrease 24 hr gastric secretion volumes No role of PPIs in on-demand therapy, as it takes 2-8 days for them to have maximum effect. FDA approved for pediatric use out of all omeprazole, lansoprazole and esomeprazole

58 Side effect of PPIs Mild side effects have been reported in up to 14% of children Most common side effects headache diarrhea constipation nausea

59 Prokinetics metoclopramide, domperidone, erythromycin, baclofen or itopride in the management of GERD prokinetics may be of some use is GERD with associated gastroparesis Vandenplas Y, et al. J Pediatr Gastroenterol Nutr 2009 Poddar U. Indian Pediatr 2013

60 Duration of medical therapy GERD needs profound acid suppression for a longer duration of time PPI therapy is recommended for at least 12 weeks and then to taper over 2 to 3 months as rebound hyperacidity after sudden stoppage of PPI No symptomatic improvement in 4 weeks then the dose of PPI needs to be increased A relapse on withdrawal of PPI, medication needs to be restarted Frequent relapses or continuous symptoms are indications for prolonged PPI therapy or surgery

61 Repeat endoscopy to document healing is indicated at the end of 12 weeks course in erosive esophagitis Prolonged PPI therapy (median 3 years and up to 12 years) is safe Full healing dose is superior to half dose in PPI maintenance therapy

62 Surgery Nissen fundoplication (open or laparoscopic) may be of benefit in children with confirmed GERD Who have failed optimal medical therapy Who are dependent on medical therapy for a long time Who are significantly noncompliant to medical therapy Who have life threatening complication of GERD Point: who need surgery most, develop surgery related complications and surgical failure most Fundoplication in early infancy has a higher failure rate than in late childhood Hassall E. Arch Dis Child 2005 Vandenplas Y, et al. J Pediatr Gastroenterol Nutr 2009 Poddar U. Indian Pediatr 2013

63 Conclusion GER is common in infants but GERD is not so common in early childhood Most infants have physiological reflux and need minimal intervention as their symptoms resolve by 18 months of age There is no gold standard diagnostic test for GERD and investigation should be tailored to the clinical concern for a given child For extraesophageal manifestations, ph-metry with or without impedance is the best investigations For esophagitis, endoscopy is the best investigations Empirical PPI therapy for 4 weeks is justified in older children and adolescents with classical symptoms Medical therapy with PPI is very effective and safe. Surgical therapy is not a panacea as it carries significant morbidity and often fails in those who need it most.

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