Gastroesophageal Reflux in Infants and Children

Transcription

1 Gastroesophageal Reflux in Infants and Children E D Nel Department of Paediatrics and Child Health, Faculty of Health Sciences, Stellenbosch University

2 Outline What is GOR? Natural History Is it GORD? Differential Diagnosis Diagnostic options Therapeutic options

3 What is GOR? GOR is the passage of gastric contents into the esophagus with or without regurgitation and vomiting.

4 Normal Anatomy of Oesophagus

5 Natural History

6 Natural History of Regurgitation in Infants Nelson (1997) Sample size Subjects Outcome measured 948 Healthy Reported infants frequency of regurgitation Results 0-3 months: 50%, 4 months: 67%, 7 months: 21%, months: 5%, Peak regurgitation as a problem for parents - 6 months (23%)

7 Which children are likely to have persistent complaints? Congenital abnormalities Oesophageal atresia Hiatal Hernia Neurological abnormalities Cystic fibrosis Family history

8 Paediatric GORD as a precursor to Adult GORD Problematic or high frequency of regurgitation: More feeding problems > 1 year (Nelson 1998) more symptoms of GORD at 9 years (Martin 2002) Persistence of histological features of GORD after resolution of symptoms in infants. (Orenstein 2006) Adults with GORD are more likely to have had GORD symptoms as children. (Waring 2002) Genetic predisposition to GORD. (Orenstein 2002) Can the progression to adult GORD be prevented?

9 Complications Is it GORD?

10 Reflux Oesophagitis

11 Is this GORD? Granuloma, Oedema, rugae formation

12 Nature of Associations Confounding GOR Disease Incidental co-occurrence of GOR and a specific complaint Many complications are due to non-acid/weakly acid GOR No effective medical treatment for GOR Non-specific complaints

13 Troublesome symptoms or complications Oesophageal ( Modified from Sherman 2009) 0-8 Years or unable to reliably report symptoms Excessive regurgitation Feeding refusal/anorexia Unexplained crying Choking/gagging/coughing Sleep disturbance Abdominal pain Cognitive ability to reliably report symptoms Typical Reflux syndrome Oesophageal Injury Reflux esophagitis Reflux stricture Barrett s esophagus Adenocarcinoma

14 Troublesome symptoms or complications Extra-oesophageal (Modified from Sherman 2009) Definite Associations Sandifer Syndrome Dental erosions Malnutrition* Possible Associations Bronchopulmonary Asthma Pulmonary fibrosis Laryngotracheal and Pharyngeal Chronic cough Hoarsenesss Rhinological and Otological Sinusitis Serous otitis media Infants Apparent lifethreatening events * Not in Sherman

15 Differential Diagnosis Anatomic/motility disorders Infections of GIT Food allergy Eosinophilic oesophagitis Raised intracranial pressure Inherited Metabolic Diseases Urinary tract infections/ abnormalities Infections Toxins/drugs Cardiac Cyclic vomiting Neglect/abuse PYLORIC STENOSIS - Barium Meal

16 Diagnostic Modalities What information does a modality provide?

17 History Obtained from care-giver in infants & young children. Typical and atypical symptoms. Search for other causes of complaints (e.g. food allergy). Validated questionnaires: Frequency Volume Discomfort Crying Food refusal Posturing Apnoea

18 Contrast Radiography Low sensitivity and specificity Useful to assess anatomy and swallowing (VFSS) Not used to make the diagnosis of GOR

19 Oesophageal Scintigraphy

20 Endoscopy

21 Endoscopy Reflux Oesophagitis Eosinophilic Oesophagitis

22 Histology Histological features of GERD Exclude other conditions Complications

23 Oesophageal ph-metry

24 Oesophageal ph-metry GI Motility online (May 2006) doi: /gimo31

25 ph-metry in Infants Acid reflux (cannot detect neutral GER) Normal values differ from adults Not accurate predictor of oesophagitis Symptom association may be useful

26 Impedance

27 Combined multichannel intraluminal impedance and ph catheter. Detect acidic and non-acidic GER Temporal association with symptoms Height of reflux episode Expensive Time consuming Experience GI Motility online (May 2006) doi: /gimo31

28 Therapeutic Options

29 Therapeutic Approach to the Treatment of GER in Infancy (Vandenplas 1997) Phase 1 Phase 2 Phase 3 Phase 4 Phase 5 A. Parental assurance B. Milk-thickening Prokinetics Adjuvant therapy - prone, head-up A. H2 blockers B. PPI Surgery

30 Recent Recommendations

31 Therapeutic Options Feeds/formula Feeding technique Over-feeding Thickening Hydrolysed formula Avoid exposure to smoking

32 Therapeutic Options Positional Therapy Prone Left or Right side SIDS

33 Therapeutic Options Prokinetics Metoclopramide Domperidone Cisapride Erithromycin

34 Therapeutic Options Alginate rafts Sucralfate

35 Therapeutic Options Increase ph Antacids H2 Antagonists

36 PPI Paediatric registration Appropriate dose Dose in children often too low Appropriate formulation Suspensions for infants & young children Require weaning rebound may occur Single daily dose usually adequate: bd dose with specific indications Not an anti-emetic Possible complications Diarrhoeal disease SBO Pneumonia

37 Therapeutic Options Surgery Morbidity/mortality Not always permanent

38

39 Case Scenario 1 You are asked to see a 10 day old infant in the neonatal ICU with the problem of recurrent apnoea. 28 weeks gestation He required ventilation for 5 days The neonatologists ask whether this could be due to GOR How would you approach this infant

40 Case Scenario 2 A 3 year old girl is referred by your ENT colleague with the complaint of hoarseness. An direct laryngoscopy showed oedema of the posterior commissure and the ENT specialist thinks that the hoarseness is due to GER How would you approach this girl?

41 Case Scenario 3 A 6 year old boy with spastic quadriplegia is referred with recurrent pneumonia. The neurologist caring for the boy has observed regurgitation after feeds and suspects that the recurrent episodes of pneumonia are due to GERD. How would you approach this patient?

42 Case Scenario 4 A 3 month old infant is referred to you by a community paediatrician. The infant has failed to gain weight for the last two months and is presently severely malnourished. She regurgitates frequently and the referring paediatrician thinks that the failure to thrive is due to GER How would you approach the referral?

43 Specific Patient Groups

44 Failure to thrive

45 Infant who is not thriving GER often associated not necessarily a causal relationship Thorough history and examination Psychosocial assessment Ba contrast study (anatomic abnormalities) Investigate for underlying diseases e.g. IMD Trial of hydrolysed formula Temporary NG tube feeds

46 Neurologically Impaired Child

47 Neurologically Impaired Children More GER Erosive oesophagitis Vomiting/wretching Poor protection of airway

48 Assessing Aspiration VFSS Aspiration often during swallowing and not due to GER (Sheik 2001)

49 Neurologically Impaired Children May require more PPI Baclofen Poor response to AR surgery

50 The Premature Infant with Apnoea

51 Premature Infant Laryngeal reflex in neonates: apnoea Poor evidence of causal association Diagnosis Treatment options Route of feeding Drug PPI H2 Antagonists Prokinetic Surgery

52 Laryngeal Disease and GER

53 GER & Airway Disease Mean number of pharyngeal reflux episodes per hour Little 1997

54 Laryngeal Complications of GER Author Diagnosis of GER Patients Outcome Bibi 2001 Barium & phmetry, bronchoscopy Laryngo- or tracheomalacia (n= 54) vs. other respiratory complaints (n= 62) 70% GER vs 39% Bouchard S ph-metry, Response to treatment ENT complaints (n=105) 80% GER with Laryngomalacia, 80% treatment response Matthews 1999 Dual probe phmetry Laryngomalacia (n= 24) 100% proximal reflux, 66% distal reflux Giannoni 1998 Ba study ph-metry Laryngomalacia (n=27) 64% GER

55 ph- Metry &Laryngeal complications of GER Rabinowitz 2003 Design Patients Outcome Retrospecti ve, Dual probe ph-metry 28 ENT complaints, 27 controls (non respiratory complaints, normal distal ph-metry) Distal & Proximal RI Patients > Controls Abnormal distal ph-metry 6/28 (21%) Abnormal proximal phmetry 15/28 (54%) Abnormal proximal phmetry but normal distal phmetry 9/28 (32%) No data on response to treatment.

56 ph- Metry &Laryngeal complications of GER Rabinowitz 2003 Standard distal ph-metry may fail to identify GER leading to upper airway disease. Children with normal distal ph-metry may respond to antireflux treatment. Normal distal ph-metry in the presence of increased proximal acid exposure may indicate disturbed motility.

57 Problems with Distal ph-metry Does not measure non-acid reflux Distal probe often normal in GER associated upper airway disease. (Little 1999)

58 Proximal ph-metry Normative data for proximal probe (Bagucka 2000) Duration of study may be too short Dual probe studies do not reliably identify patients who will respond to anti-reflux treatment. Poor correlation between proximal probe acid exposure and laryngeal histology (McMurray 2001) Poorly reproducible! (Vaezi 1997) Placement of proximal probe

59 Other diagnostic options Impedance Laryngoscopy/videostroboscopy Histology (oesophageal, laryngeal) Laryngeal reflexes: videofluoroscopy, Sensory threshold (FEES) Scintigraphy Barium study Symptoms

60 Treatment of LPR Disease in Adults Less responsive to treatment than typical GERD Less likely to respond to life style modification PPI Effective in some adults High dose, twice daily Response after 2-4 months Prolonged treatment required (6 months or more)

61 How do children respond to treatment? No RCT for laryngeal disease.

62 Management of a child or infant with suspected GER related laryngeal disease Thorough investigation for other causes of laryngeal disease Cooperation between ENT & GIT Trial of treatment Dictated by Severity Failure (PPI or H2 antagonist) Response Establish effective PPI/H2 antagonist treatment Re-examine: other causes of laryngeal disease Examine for acid exposure Continue Withdraw after months Surgery? Prolonged medical treatment, increased dose Surgery

63 Asthma & GER

64 Supraesophageal Complications of GERD Sinusitis, Otalgia, Sialorrhea Tooth erosion Pharyngitis SIDS Vocal cord ulcer, granuloma, dysphonia, hoarseness Cricoarytenoid arthritis Laryngitis, subglottic stenosis Cough Pneumonia Asthma

65 Prevalence of GER in Asthma Adults (ph-metry) Author Sample n Controls GER% 1988 Ducolone Nagel Nocturnal asthma 1988 Ekstrom Nocturnal Asthma No assoc. between GER & early morning dipping Correlation between GER and morning airway obstruction 1989 Luo In patients with GER symptoms - 88% had GER 1993 Herve Chronic asthma High dose theophylline and duration of disease corr. with risk of GER 1994 Gastal Non-cardiac pain - 54% GER 1997 Campo More GER when sleeping & supine

66 Prevalence of GER in Asthma Children (ph-metry) Author Sample n Controls GER % 1983 Hughes 9 7 No difference in parameters 1985 Wilson Moderate to severe asthma Buts Recurrent respiratory disorders 1993 Tucci Uncontrolled asthma Reflux time 40* greater in asthma & laryngitis than controls 1993 Tucci Asthma Blecker Chronic resp 62 63

67 Prevalence of GER in Asthma A high proportion of patients with asthma have objective evidence of GER in excess of that found in the general population (30-60%). Patients with moderate to severe asthma have a higher prevalence of GER. In the presence of chest pain (adults) the prevalence of GER is increased. Nocturnal GER is associated with increased airway resistance in the morning The prevalence of GER is also increased in other chronic respiratory diseases. Caveat Samples not truly representative of all asthmatics ( selection bias).

68 GER Causes or Aggravates Asthma Aspiration Reflex bronchospasm - secondary to acid reflux into the lower esophagus

69 GER Asthma Possible Mechanisms Aspiration Reflex increase in airway resistance or reactivity ( neural?) Inflammatory mediators

70 Aspiration Theory Scintigraphy Dual probe ph-metry or proximal ph probe

71 Aspiration Scintigraphy Author Sample n Aspiration % 1986 Veyrac Adults: Asthma & GER symptoms 55 25% 1988 Ducolone Adults: Asthma, Chronic bronchitis 1993 Ruth Adults: Chronic respiratory disorders and GER symptoms 51 12% 55 20% 1994 Dai Adults: Asthma 32 (38% GER) 0%

72 Aspiration Dual Probe ph-metry Author Sample n Results 1995 Harding Adults: Asthma & GER 1995 Cucchiara Children: Respiratory symptoms and symptoms of GER 1995 Jack Adults: Asthma & symptomatic GER 20 Acid infusion associated with decreased PEFR. Not associated with change in ph in proximal esophagus 40 Respiratory symptoms correlated with ph in distal esophagus, no correlation with proximal esophagus ph 4 Simultaneous tracheal & esophageal ph probe: 5/37 GER episodes associated with fall in tracheal phand a greater decrease in PEFR.

73 Asthmatic/ wheezy Child

74 Association Between Asthma and GER? Nature of the Association GER causes or aggravates asthma Asthma causes or aggravates GER Spurious association

75 Who may benefit from investigation and treatment? Severe or poorly controlled asthma Symptomatic GER Nocturnal Asthma Esophagitis Thorough assessment for other causes of respiratory symptoms!

76 Prevalence of GER in Asthma Children (ph-metry) Author Sample n Controls GER % 1983 Hughes 9 7 No difference in parameters 1985 Wilson Moderate to severe asthma Buts Recurrent respiratory disorders 1993 Tucci Uncontrolled asthma Reflux time 40* greater in asthma & laryngitis than controls 1993 Tucci Asthma Blecker Chronic resp 62 63

77 Prevalence of GER in Asthma Children (ph-metry) Cinquetti, M children, recurrent/therapy resistant asthma 61% RFI>4,2%

78 Prevalence of GER in Asthma A high proportion of patients with asthma have objective evidence of GER in excess of that found in the general population (30-60%). Patients with moderate to severe asthma have a higher prevalence of GER. In the presence of chest pain (adults) the prevalence of GER is increased. Nocturnal GER is associated with increased airway resistance in the morning The prevalence of GER is also increased in other chronic respiratory diseases. Caveat Samples not truly representative of all asthmatics ( selection bias).

79 Anti-reflux Surgery Children with Asthma or Chronic Respiratory Disease Author Sample n 1987 Eizguirre GER & Resp. disease ( recurrent bronchitis, asthma, chronic cough) 1989 Petru Moderate-severe asthma 45 60% cured 20% improved Failure more common in those with no GER symptoms 11 36% successfull 45% partly successfull 1991 Andze Severe asthmatics, unresponsive to medical treatment 33 88% improved Less successfull in patients without GER symptoms

80 Acid Perfusion Studies Adult Asthmatics Author n 1989 Ekstrom 8 Subclinical bronchoconstriction, increased histamine reactivity 1993 Wesseling 12 No change in FEV1 or impedance 1995 Harding 20 Decreased PEFR & increased airway resistance - persisted after acid clearance 1982 Spaulding Increased airway resistance - greatest in patients with GER symptoms 1985 Perpina 21 Only patients with symptomatic GER showed significant change in lung function 1994 Schan 27 PEFR decreased in all. Patients with symptomatic GER decrease persisted after acid clearance 1986 Herve Bronchoconstriction induced by hyperventilation or metacholine increased 1995 Chakrabarti 15 FEV1 & FVC decreased. All patients with nocturnal asthma became symptomatic

81 Acid perfusion Studies Asthma in childhood Author Sample n 1983 Davis Nocturnal Asthma & GER 1985 Wilson Moderate to severe asthma 9 Respiratory rate and wheezing increased in those with a positive Bernstein 18 11/18 (61%) increase in histamine sensitivity. No change in PEFR

82 Conclusions GER Asthma GER increases airway reactivity and resistance in some patients with asthma. These effects are the most pronounced in patients with symptomatic GER, a positive Bernstein test, or nocturnal asthma

83 GER as a Cause or Aggravating Factor in Asthma Aspiration occurs in some patients with asthma but is not demonstrated in the majority. Reflex neural mechanisms may account for increased airway reactivity and resistance.

84 Effect of Prokinetic Drugs in Children with Chronic Respiratory Disease Author Sample n 1989 Saye GER associated bronchopulmonary disease 19 In 12/13 cough fits disappeared 1989 Du Pont Asthma & GER 18 Decreased asthma symptoms 1993 Tucci Uncontrolled asthma with GER 1995 Blecker Chronic respiratory disease with GER 27 70% asthma symptoms improved, drug use decreased 39 85% improved

85 H 2 Antagonists Gustafsson (1992) Patients 37 Asthmatic children (18/37 abnormal ph-metry) Intervention Ranitidine to all patients Results GER patients 30% improvement in nocturnal symptoms in comparison to non-ger patients Correlation between degree of improvement and acid reflux

86 Anti-reflux Surgery Children with Asthma or Chronic Respiratory Disease Author Sample n 1987 Eizguirre GER & Resp. disease ( recurrent bronchitis, asthma, chronic cough) 1989 Petru Moderate-severe asthma 45 60% cured 20% improved Failure more common in those with no GER symptoms 11 36% successfull 45% partly successfull 1991 Andze Severe asthmatics, unresponsive to medical treatment 33 88% improved Less successfull in patients without GER symptoms

87 Who may benefit from investigation and treatment? Severe or poorly controlled asthma Symptomatic GER Nocturnal Asthma Esophagitis

88 Asthma and GER Is there an association between GER and asthma? OR Does the prevalence of GER in asthma differ from that in non-asthmatics? What is the nature of this association? What are the implcations for treatment? OR Who will benefit from investigation and treatment?

89 When to treat? Establish a temporal relationship between respiratory symptoms and episodes of GER. Therapeutic trial. Single patient placebo controlled trial.

90 Gastroesophageal Reflux in infants With Wheezing Sheikh (1999) Sample 84 Infants (8.7 months) Difficult to control wheezing > 3months Investigation Treatment 54 (64%) abnormal ph-metry Treated for GER Results Hospital & Emergency Room visits Decrease over time No difference between groups Medication Less patients required medication in GER group (18m follw-up)

91 GER & The Upper Airway Challenging and Frustrating! Nasal passa Larynx UES Oesophagus LES Stomach