Servicio de Gastroenterología - Hepatología y Trasplante ... Hepato Nutri/PDFs/Orsi... ·...

Dra Marina Orsi

Servicio de Gastroenterologiacutea-Hepatologiacutea y Trasplante

Hepatointestinal Pediaacutetricomarinaorsihibaorgar

Dra Marina Orsi

IMPEDANCIOMETRIA INTRALUMINAL MULTICANAL de 24 HS

iquestLA OBSOLESENCIA DE LA PHMETRIA

V Congreso Argentino de Gastroenterologiacutea ndashHepatologiacutea ndash Nutricioacuten

Curso Posgrado Gastroenterologiacutea ndashHepatologiacutea ndash Nutricioacuten

Hospital Italiano de Buenos AiresServicio de Gastroenterologiacutea y Hepatologiacutea Infantil

Centro de Trasplante Hepaacutetico-Intestinal Pediaacutetrico GRACIAS

Objetivos

Conocer los fundamentos de la Impedanciometria Intraluminal Multicanal

Reconocer su utilidad cliacutenica ventajas y limitaciones

Analizar lugar que hoy y en el futuro proacuteximo le cabe a la ph y a la IIM en nuestro medio

Tiacutetulo

Cuadro e historia cliacutenicaSeriada Gastroduodenal bajo radioscopiacuteaVideo-Deglucioacuten con SGDEndoscopiacutea alta con biopsiaspHmetriacutea de 24 horas ManometriacuteaGamma-camaraImpedanciometriacutea Intraluminal Multicanal con phmetrigravea de 24 hs o manometria

DIAGNOacuteSTICO

Enfermedad por Reflujo GastroesofaacutegicoERGE

Es el lactante o nintildeo con siacutentomas digestivos yo extradigestivos que se vinculan al dantildeo tisularproducido por la intensidad o frecuencia de los episodios de reflujo

Altera su calidad de vida

Se denomina Reflujo Gastroesofaacutegico Patoloacutegico

Regurgitador o ldquovomitador felizrdquo

Es el lactante que regurgita yo vomita con variable intensidad sin otro siacutentoma acompantildeante

No altera su calidad de vida

Crece bien y esta sonriente

Tiene Reflujo Gastroesofaacutegico Fisioloacutegico

NO EFECTUAR PROCEDIMIENTOS

IIM-PH DE 24 HS

Queacute es la IMPEDANCIA

RESISTENCIA AL FLUJO CORRIENTEMedicioacuten inversa de la conductividad eleacutectrica de lapared de un oacutergano o su contenido

POR QUEacute CAMBIA LA IMPEDANCIA

No hay bolo = pocos iones = alta impedancia

Bolo presente= muchos iones =impedancia baja

IIM-PH DE 24 HS

Entrada del Bolus

Salida del Bolus

Impe

danc

ia

Tiempo

Bolus Presente

IIM Detecta el movimiento del bolus

Tragar Reflujo

Bolus Entry Movimiento del bolus

Movimiento del bolus

Bolus Entry

Bolus Entry

Bolus Entry

Bolus Entry

Bolus Entry Bolus Entry

Bolus Entry

Bolus Entry

Bolus Entry

Bolus Entry

Bolus Entry

Fundamentos de la Impedancia

IIM-PH de 24 HSUtilidad de la monitorizacioacuten con IIM-pH 24 hs

Detecta reflujo Aacutecido No Aacutecido y Debilmente Aacutecido

Puede establecer diagnoacutestico en pacientes con siacutentomas refractarios durante el tratamiento meacutedico

Permite evaluarlos con o sin medicacioacuten

Correlaciona siacutentomas con episodios Aacutecidos y No Aacutecidos

Permite estudiar paraacutemetros de motilidad esofaacutegica


Cuantifica el patroacuten de reflujo y la correlacioacutensintomaacutetica tambieacuten en el periacuteodo post-prandial

Mide la altura que alcanzan los reflujos Aacutecidos Debilmente Aacutecidos y No Aacutecidos

Es capaz de diagnosticar el reflujo supra-esofaacutegico (canales proximales)

Puede monitorear a los lactantes pequentildeos con alimentacioacuten No Aacutecida muy frecuente

Permite estudiar pacientes con siacutentomas extradigestivos

IIM-PH de 24 HSDATOS UacuteTILES DEL INFORME

Correlacioacuten sintomaacutetica (SI)Es el porcentaje de episodios sintomaacuteticos relacionados con reflujo Se considera positivo cuando es igual o mayor al 50

Probabilidad de asociacioacuten sintomaacutetica(SAP)Caacutelculo de la relacioacuten estadiacutestica entre los siacutentomas y los episodios de reflujo mediante la prueba exacta de FisherSe calcula dividiendo el total del estudio de 24 hs en segmentos de cada dos minutosEn cada segmento se determina si hubo eventos de reflujo o siacutentomas relacionadosSe considera positivo cuando es mayor o igual al 95

Ambos paraacutemetros importantes en pacientes con EAAV BOR tos recurrente


Datos sobre pHmetriacutea de 24hs (score episodio maacutes prolongado cantidad total de episodios)

Cuantificacioacuten de reflujos aacutecidos y no aacutecidos(relevante en pacientes bajo tto con IBP BOR lactantes)

Clearance del bolo (relevante en pacientes con alt de la motilidad esofaacutegica-atresiasacalasia)

Cuantificacioacuten de reflujos que alcanzan canales proximales (relevante en pacientes con siacutentomas extradigestivos- BOR tos recurrente laringitis a repeticioacuten)

Reflujo No Acido

RESULTADOS

9

Impedance ndashpH Catheter

3 cm

5 cm

7 cm

9 cm

11 cm

13 cm

pH ndash 3 cm

Pediatric Model6 impedance channels

1 pH channel

16

True GER Episode

Leave MII Measurement

Review Study to Verify MII Reflux Episodes Preceding Symptoms

17

Acid GER 2Acid GER 1

pH Remains Below 40

Acid ReReflux

Historia

bull Publicaciones desde 1996 en JPGN hasta la actualidad

bull Trabajos en Pediatrics Journal of Pediatrics Archives Disease of Childhood Gut American Journal of Gastroenterology helliphelliphelliphellip

bull Buacutesquedas 192 trabajos con 32 review adultos y nintildeos

bull En Pediatria 127 trabajos con 7 Review

PHMETRIacuteA DE 24 HS

Considerada la ldquoprueba de orordquo desde la deacutecada del 80 para establecer el Dx de RGE patoloacutegico

Es un meacutetodo indirecto que se basa en la medicioacuten del pH en esoacutefago

Meacutetodo miacutenimamente invasivo bien tolerado por los nintildeos

No requiere anestesia ni de un entorno de complejidad para su realizacioacuten

Detecta exclusivamente episodios aacutecidos

65 de reproduciblidad

Mahajan L Wyllie R Oliva L et al Reproducibility of 24-hour intraesophageal pH monitoringin pediatric patients Pediatrics 1998101260ndash3

Vandenplas Y Helven R Goyvaerts H et al Reproducibility of continuous 24 hour oesophageal pH monitoring in infants and children (see comments) Gut 199031374ndash7

Bibliografiacutea pHmetriacutea de 24 hsbull Boix-Ochoa J Lafuenta JM Gil-Vernet JM Twenty-four hour esophageal pH monitoring in

gastroesophageal reflux J PediatrSurg 19801574ndash8

bull Vandenplas Y Derde MP Piepsz A Evaluation of reflux episodes during simultaneous esophageal pH monitoring and gastroesophageal reflux scintigraphy in children J Pediatr Gastroenterol Nutr 199214256ndash60

bull Vandenplas Y Sacre-Smits L Continuous 24-hour esophageal pH monitoring in 285 asymptomatic infants 0ndash15 months old J Pediatr Gastroenterol Nutr 19876220ndash4

bull Vandenplas Y Badriul H Verghote M et al Oesophageal pH monitoring and reflux oesophagitis in irritable infants Eur J Pediatr 2004163300ndash4

bull Sondheimer JM Continuous monitoring of distal esophageal pH a diagnostic test for gastroesophageal reflux in infants J Pediatr 198096804ndash7

bull Cucchiara S Staiano A Gobio Casali L et al Value of the 24 hour intraoesophageal pH monitoring in children Gut 199031129ndash33

pHmetriacutea de 24 horas ( Guidelines ESPGHAN-NASPGHAN 2009 )

This test is a valid quantitative measure of esophageal acid exposure with established normal ranges

In pH studies performed with antimony electrodes an RI gt 7 is considered abnormal an RI lt 3 is considered normal and anRI between 3 and 7 is indeterminate

However the severity of pathologic acid reflux does not correlate consistently with symptom severity or demonstrable complications

In children with documented esophagitis normal esophageal pH monitoring suggests a diagnosis other than GERD

pHmetriacutea de 24 horas ( Guidelines 2009 )

bull Esophageal pH monitoring is useful for evaluating the efficacy of antisecretory therapy

bull It may be useful to correlate symptoms (eg cough chest pain) with acid reflux episodes and to select those infants and children with wheezing or respiratory symptoms in whom GER is an aggravating factor

bull The sensitivity specificity and clinical utility of pH monitoring for diagnosis and management of possible extraesophageal complications of GER are not well established

pHmetriacutea en un lactante con RGE severo y correlacioacuten Sx

1ordf pH

2ordf pH

3ordf pH

IR282

IR69

IR18

A

Correlacioacuten sintomaacutetica apnea - rge

pnea

Obituary The Death of the pH ProbeTHE JOURNAL OF PEDIATRICS December 2010- Vol 157 No 6e

Philip E Putnam MD Cincinnati Childrenrsquos Hospital Medical Center Cincinnati Ohio

bull Gastric acid was just a few centimeters away on the other side of the lower esophageal sphincter that was designed to keep it there and any that escaped into the esophagus was detected

bull Acid reflux episodes could be counted timed and associated with all sorts of stuff We knew what was lsquolsquonormalrsquorsquo



bull No matter that reflux of material with any pH above 4 could not be detected

bull Never mind that food in the stomach neutralized gastric acid and provided a buffer against re acidification for some time after a meal such that postprandial reflux arguably the most common was most often not detectable

bull Correlation between the result of pH-metry and symptoms and with the impact of the observed reflux

bull The author has no interest financial or otherwise in any company that makes or promotes either pH probes or MII pH catheters

bull As an institution we abandoned pH-metry in favor of MII-pH more than 5 years ago on the basis of the logic of the concept and early studies

IIM-PH de 24 HS

pH

IIM

IIM-PH de 24 HSPUBLICACIONES

Primeras publicaciones desde 1996 hasta la actualidad

The Importance of Multichannel Intraluminal Impedance in the Evaluation of Children with Persistent RespiratorySymptoms

Rachel Rosen MD MPH and Samuel Nurko MD MPHMotility Unit Division of Gastroenterology and Nutrition Childrenrsquos Hospital Boston Harvard MedicalSchool Boston Massachusetts

OBJECTIVES Previous evidence suggests an association between gastroesophageal reflux disease and chronicrespiratory disease in children Despite antisecretory antacid therapy respiratory symptoms often persist supporting a role for nonacid reflux

The aim of this study was To determine whether nonacid reflux occurs in children with chronic respiratory disease

METHODS Twenty-eight children (mean age 65 plusmn 56 yr) with persistent respiratory symptoms on antacid medications underwent 24 h pHmultichannel intraluminal impedance (pHMII) recordingThe symptom index (SI) and the symptom sensitivity index (SSI) were calculated for each patientLogistic regression was performed to determine which reflux characteristics were associated with a high degree of symptom correlation present during the occurrence of symptoms

(Am J Gastroenterol 2004992452ndash2458)

RESULTS A total of 1822 reflux episodes were detected by pHMII 45 of which were nonacidic The mean SI increased using pHMII (357 plusmn 285) compared to pH probe alone (146 plusmn 189 p = 0002) no differences in the mean SSI using pHMII compared to pH probe alone were identified Significantly more patients had a positive SI using pHMII than pH probe alone (p = 0035) there was no difference in the number of patients with a positive SSI using pHMII compared to pH probe aloneMultivariate analysis revealed that symptoms occurred more frequently when the reflux was nonacidic mixed and full column Also younger children were more likely to have the simultaneous occurrence of symptoms and reflux

CONCLUSIONS Nonacid reflux may be an important predictor of respiratory symptoms pHMII provided important nformation in the evaluation of children with intractable respiratory symptoms




American Journal of Gastroenterology ISSN 0002-9270 2007 by Am Coll of Gastroenterology doi 101111j1572-0241200600936x Published by Blackwell Publishing PRACTICE GUIDELINES

ACG Practice Guidelines Esophageal Reflux Testing Ikuo Hirano MD1 Joel E Richter MD2 and the Practice Parameters Committee of the AmericanGastroenterology Division of Gastroenterology Northwestern University Feinberg School of Medicine Chicago Illinois and 2Department of Medicine Temple University School of Medicine Philadelphia Pennsylvania

Investigations and technical advances have enhanced our understanding and management of gastroesophageal reflux disease The recognition of the prevalence and importance of patients with endoscopy-negative reflux disease as well as those refractory to proton pump inhibitor therapy have led to an increasing need for objective tests of esophageal reflux Guidelines for esophageal reflux testing are developed under the auspices of the American College of Gastroenterology and its Practice Parameters Committee and approved by the Board of Trustees Issues regarding the utilization of conventional catheter-based pH monitoring are discussed Improvements in the interpretation of esophageal pH recordings through the use of symptom-reflux association analyses as well as limitations gleaned from recent studies are reviewed The clinical utility of pH recordings in the proximal esophagus and stomach is examined

Newly introduced techniques of duodeno-gastroesophageal reflux wireless pH capsule monitoring and esophageal impedance testing are assessed and put into the context of traditional methodology Finally recommendations on the clinical applications of esophageal reflux testing are presented


Combined multichannel intraluminal impedance-pH monitoring to selectpatients with persistent gastro-oesophageal reflux for laparoscopic Nissen

fundoplicationI Mainie 1 R Tutuian 1 A Agrawal 1 D Adams 2 D O Castell 1 1Division of Gastroenterology and Hepatology Medical University of South Carolina Charleston South CarolinaUSA 2Department of Surgery Medical University of South Carolina Charleston South Carolina USA

ABSTRACTBackgroundCombined multichannel intraluminal impedance-pH (MII-pH) monitoring detects gastro-oesophageal reflux and identifies acid and non-acid reflux events It can be used in patients with persistent symptoms on proton-pump inhibitor (PPI) therapy

The aim of this study was to assess laparoscopic Nissen fundoplication as a treatment for patients with persistent symptoms associated with reflux despite acid suppression documented by MII-pH monitoring

MethodA prospectively maintained database identified patients with persistent symptoms of gastro-oesophageal refluxdisease despite PPI therapy who had undergone MII-pH monitoring and this was cross-referenced with patients whohad undergone fundoplication at this institution Follow-up after fundoplication was by periodic telephone interviewand review of clinical records


fundoplicationI Mainie 1 R Tutuian 1 A Agrawal 1 D Adams 2 D O Castell 1

1Division of Gastroenterology and Hepatology Medical University of South Carolina Charleston South CarolinaUSA 2Department of Surgery Medical University of South Carolina Charleston South Carolina USA

bull Resultsbull Of 200 evaluated patients 19 (14 female mean age 40 (range 07-78) years)

underwent laparoscopic Nissen fundoplication Before surgery 18 of 19 patients had a positive symptom index (at least half of symptoms associated with reflux) and one a negative symptom index After a mean follow-up of 14 (range 7-25) months 16 of 17 (94 percent) patients with a positive symptom index were asymptomatic or markedly improved (one patient was lost tofollow-up) Persistent symptoms occurred in the patient with a negative symptom index and one patient had recurrent symptoms after 9 months

bull Conclusionbull Patients with a positive symptom index resistant to PPIs with non-acid or acid

reflux demonstrated by MII-pHmonitoring can be treated successfully by laparoscopic Nissen fundoplication

bull 2006 British Journal of Surgery

Combined MultiChannel Intraluminal Impedance and pH Esophageal Testing Compared to pH Alone for Diagnosing Both Acid and Weakly Acidic

Gastroesophageal RefluxHila A Agrawal A Castell DO

Clinical Gastroenterology and Hepatology 2007 5 172-77

bull The most common reason pH only overstated acid reflux was pH drops associated with swallows (81 of patients had acid swallows despite being instructed to not ingest acidic beverages outside of meal periods)

bull Acid pH monitoring specificity for acid symptom index calculation was 67 as compared to MII-pH

bull This is to state a significant trait for acid pH monitoring to overstate acid reflux resulting in overstating the temporal association of acid reflux to symptoms This is critical in that Symptom Index (SI) is frequently the primary basis of study interpretation

bull The study concludes ldquoThe use of pH alone for the detection of acid reflux is very sensitive but lacks specificity compared with MII-pH pH alone may over-diagnose abnormal acid reflux in up to 22 of tested patients

bull Also the use of pH for the detection of weakly acid reflux has poor sensitivityrdquo

REVIEW Esophageal Impedance Monitoring for

Gastroesophageal RefluxHayat M Mousa yRachel Rosen Frederick W Woodley zMarina Orsi sectDaniela Armas

jjChristophe Faure John Fortunato Judith OrsquoConnor Beth Skaggs and ySamuel Nurko

bull Dual pH-multichannel intraluminal impedance (pH-MII) is a sensitive tool for evaluating overall gastroesophageal reflux disease and particularly for permitting detection of nonacid reflux events pH-MII technology is especially useful in the postprandial period or at other times when gastric contents are nonacidic pH-MII was recently recognized by the North American Society for Pediatric Gastroenterology Hepatology and Nutrition and theEuropean Society for Pediatric Gastroenterology Hepatology and Nutrition as being superior to pH monitoring alone for evaluation of the temporal relation between symptoms and gastroesophageal reflux

bull In children Ph-MII is useful to correlate symptoms with reflux (particularly nonacid reflux)to quantify reflux during tube feedings and the postprandial period and to assess efficacy of antireflux therapy

bull This clinical review is simply an evidence-based overview addressing the indications limitations and recommended protocol for the clinical use of pH-MII in children JPGN Volume 52 Number 2 February 2011

REVISIOacuteNMonitoreo esofaacutegico por

impedanciometriacutea para el reflujo gastroesofaacutegico

Hayat M Mousa Rachel Rosen Frederick W Woodley DaggerMarina Orsi sectDaneila Armas II Christophe Faure para John Fortunato JudithOrsquoConnor Beth Skaggs y Samuel Nurko

bull Original publicado en Journal of Pediatric Gastroenterology and Nutrition (JPGN 201152129-139)

bull Recibido el 8 de marzo de 2010 aceptado el 2 de octubre de 2010bull Department of Pediatric Gastroenterology Center for Advanced Research in Neuromuscular Gastrointestinal

Disorders NationwideChildrenrsquos Hospital Ohio State University Columbus OHbull Center for Motility and Functional Gastrointestinal Disorders Childrenrsquos Hospital Boston MAbull Dagger Hospital Italiano Buenos Aires Argentinasect Hospital Britanicao Montevido Uruguaybull II Service de Gastroenterologie Hepatologie et Nutrition Peacutediatriques Hoacutespital Sainte-Justine Montreal Canadabull para Department of Pediatrics Division of Pediatric Gastroenterology Wake Forest University School of Medicine Winston-

Salem NC Financiado por NIH grants K24DK82792-1 (SN) y K23DK073713-01 (RR)bull Los autores no informan ninguacuten conflicto de intereacutesbull Copyright 2011 por European Society for Pediatric Gastroenterology Hepatology and Nutrition and North American

Society for Pediatric DOI 101097MPG0b013e3181ffde67bull 60 Acta Gastroenteroloacutegica Latinoamericana ndash Vol 41 Ndeg 2 Junio 2011

bull Acta Gastroenterol Latinoam 2011 42 00-00

No particular sequence of events is observed in infants with ALTE and Gastroesophageal Reflux as measured by Impedance

Cohen Sabban J Fernandez Cuevas V Orsi M Donato G Busoni V DacuteAgostino DPediatric Gastroenterology Unit Hospital Italiano-Buenos Aires-Argentina

The etiology of apparent life threatening events (ALTE) continues to be controversial Whether gastroesophageal reflux (GER) is cause consequence or just concurrent is still undetermined The 24 hr Multichannel Intraluminal ImpedancendashpH monitoring (MII-pH) enables the study of the quality acid or non acid and symptom correlation The analysis of the temporal sequence when this association occurs may be helpful in elucidating this issueAim To determine the temporal relation between GER episodes and ALTE in a three minute interval during a 24 hr recording



bull Materials and Methods Between March 2005 and May 2009 all former full term infants who presented with an apparent life-threatening event (ALTE) on whom we were consulted underwent a 24 hr Multichannel Intraluminal Impedance- pH study (MII-pH) using a Sandhill Monitoring Recorder Exclusion criteria were congenital anomalies ventilatory support treatment with caffeine andor need for a nasogastric tube In those in whom an episode of GER occurred within 3 min of one of apnea the temporal relationship between them was performed to determine if apneas occurred before duringor after the episode of GER

Results Fifty eight infants were evaluated (32 girls) with a median age of 2 months (r1-6 months) A total of 3011 (X 483 r 13-107) reflux events were observed 1807 (60) nonacid (X 295 r 5-105) and 1204 acid reflux (X 194 r 5-43) According to the symptom index (SI) 31 patients were positive with 70 apneas GER events detected

The percentage of apneas seen before a reflux episode was 342 (708 nonacid) during GER 328 (652 nonacid) and after GER 328 (434 nonacid) In 18 patients who experienced more than one episode of apnea during the recording a different temporal relationship with GER was observed at each one



Journal of Pediatric Gastroenterology and Nutrition49E1ndashE103 2009


Cohen Sabban J Fernandez Cuevas V Orsi M Donato G Busoni V DacuteAgostino D

Pediatric Gastroenterology Unit Hospital Italiano-Buenos Aires-Argentina

bull Conclusions In infants in whom a temporal association( ALTEGER ) was observed there was

bull no unique pattern in the symptom sequence and in bull the same patient a different sequence of events could be detected

bull This heterogenous behavior may reinforce the theory that GER and ALTE are just concurrent events

bull Journal of Pediatric Gastroenterology and Nutrition49E1ndashE103 2009



Cohen Sabban J Fernandez Cuevas V Orsi M Donato G Busoni V DacuteAgostino DPediatric Gastroenterology Unit Hospital Italiano-Buenos Aires-ArgentinaThe etiology of apparent life threatening events (ALTE) continues to be controversial Whether gastroesophageal reflux (GER) is cause consequence or just concurrent is still undetermined The 24 hr Multichannel Intraluminal ImpedancendashpH monitoring (MII-pH) enables the study of the quality acid or non acid and symptom correlation The analysis of the temporal sequence when this association occurs may be helpful in elucidating this issueAim To determine the temporal relation between GER episodes and ALTE in a three minute interval during a 24 hr recordingMaterials and Methods Between March 2005 and May 2009 all former full term infants who presented with an apparent life-threatening event (ALTE) on whom we were consulted underwent a 24 hr Multichannel Intraluminal Impedance- pH study (MII-pH) using a Sandhill Monitoring Recorder Exclusion criteria were congenital anomalies ventilatory support treatment with caffeine andor need for a nasogastric tube In those in whom an episode of GER occurred within 3 min of one of apnea the temporal relationship between them was performed to determine if apneas occurred before during or after the episode of GERResults Fifty eight infants were evaluated (32 girls) with a median age of 2 months (r1-6 months) A total of 3011 (X 483 r 13-107) reflux events were observed 1807 (60) nonacid (X 295 r 5-105) and 1204 acid reflux (X 194 r 5-43) According to the symptom index (SI) 31 patients were positive with 70 apneas GER events detected The percentage of apneas seen before a reflux episode was 342 (708 nonacid) during GER 328 (652 nonacid) and after GER 328 (434 nonacid) In 18 patients who experienced more than one episode of apnea during the recording a different temporal relationship with GER was observed at each one Conclusions In infants in whom a temporal association ( ALTE GER ) was observed there was no unique pattern in the symptom sequence and in the same patient a different sequence of events could be detectedThis heterogenous behavior may reinforce the theory that GER and ALTE are just concurrent events


Resultados El porcentaje de apneas observadas antes de un episodio de reflujo fue del 342 (el 708 no aacutecido) durante GER 328 (el 652 no aacutecido) y despueacutes de GER 328(el 434 no aacutecido) Conclusiones En los recieacuten nacidos en los que se observoacute una asociacioacuten temporal (ALTE GER) no hubo un patroacuten uacutenico en la secuencia de los siacutentomas y en el mismo paciente una secuencia diferente de los hechos podriacutea ser detectado Este comportamiento heterogeacuteneo puede reforzar la teoriacutea de que GER y ALTE son soacutelo eventos simultaacuteneos

INTRODUCCIOacuteN

En estudios con modelos animales y en adultos se ha sugerido que la determinacioacuten de la liacutenea basal (LB) de la Impedanciometriacutea Intraluminal Multicanal esofaacutegica (IIM pH) de 24 horas podriacutea reflejar la integridad de la mucosa esofaacutegica teniendo eacutesta menor valor de impedancia en pacientes con esofagitis respecto a aquellos con mucosa normal

La liacutenea basal se refiere a la sentildeal de impedancia que se observa cuando el esoacutefago se encuentra en reposo Esta sentildeal reflejariacutea la conductividad de la mucosa esofaacutegica


Puede aportar datos acerca del dantildeo de la mucosa esofaacutegica a traves de la liacutenea basal


Permitiriacutea diferenciar pacientes con y sin esofagitis

Linea basal


bull Ricard Farreacute Kathleen Blondeau Dominique Clement Maria VicarioLucio Cardozo Michael Vieth Veerle Mertens Ans Pauwels Jiri SilnyMarcel Jimenez Jan Tack Daniel Sifrim Evaluation of oesophageal mucosa integrity by the intraluminal impedance techniqueGut (2011)

bull CMLootsRWijnakkerM PVan WijkG Davidson M A Benninga amp T IOmari Esophageal impedance baselines in infants before and after placebo and proton pump inhibitor therapyNeurogastroenterol Motil (2012) 24 758ndashe352

bull OBorrelli S Salvatore V Mancini M Ribolsi M GentilendashB Bizzari M CicalaK J Lindley amp G L De Angelis Relationship between baseline impedance levels and esophageal mucosal integrity in children with erosive and non-erosive reflux disease Neurogastroenterol Motil (2012) 24 828ndashe394


En nintildeos los valores de la liacutenea basal de la impedanciometria Intraluminal Multicanal de 24 hs puede reflejar esofagitis

Cohen SabbanJ DonatoG ordm ChristensenS ordf DavilaMT OrsiM Servicio de Gastroenterologiacutea y Hepatologiacutea Pediaacutetrica Centro de Trasplante Hepaacutetico Hospital Italiano Buenos Aires ordfServicio de

Anatomia Patoloacutegica Hospital JP Garrahan ordm Servicio de Anatomia Patoloacutegica de Hospital Italiano de Buenos Aires Argentina

Introduccioacuten En publicaciones internacionales se ha mostrado que la determinacioacuten de la liacutenea basal (LB) de Impedanciometriacutea Intraluminal Multicanal (IIM pH) 24 hs podriacutea reflejar la integridad de la mucosa siendo eacutesta menor en pacientes con esofagitis respecto a aquellos con mucosa normalObjetivoComparar los valores de la liacutenea basal(LB)de la IIMpH 24 hs en nintildeos con y sin esofagitisMateriales y Meacutetodos Se realizoacute en forma restrospectiva la revisioacuten de los trazados de IIMpH24 hs realizadas entre mayo 2008 y octubre 2013 en nintildeos de 3 a 17 antildeos de edad con sospecha de reflujo gastroesofaacutegico(RGE) A todos los pacientes se les habiacutea realizado en forma conjunta videoendoscopiacutea digestiva alta(VEDA) con toma de biopsias esofaacutegicas seguido de un estudio de IIMpH24 hs La media de la liacutenea basal se calculoacute en forma automaacutetica por software especiacutefico en los diferentes canales de IIM Se utilizoacute como meacutetodo estadiacutestico el T-test Se excluyeron pacientes con esofagitis eosinofiacutelicaResultados Fueron evaluados los trazados de IIMPh 24 hs de 84 nintildeos 50 varones La edad media de los nintildeos fue de 74 antildeos En 4284 en la VEDA se observoacute esofagitis que la histologiacutea caracterizoacute en leve y moderadasevera Esofagitis leve (EL) se observoacute en 31 y 11 presentaron esofagitis de moderada a severa (ES) En los canales distales la LB de IIM fue significativamente menor (P= lt005) en los pacientes con esofagitis en comparacioacuten con aquellos con mucosa normal Asi tambien al comparar las ES vs EL observando una p=0000Conclusiones En nintildeos la evaluacioacuten de la LB de IIM resulta un buen predictor de la integridad de la mucosa esofaacutegica Este meacutetodo ambulatorio y miacutenimamente invasivo permite una mejor seleccioacuten de nintildeos que requeriraacuten endoscopiacutea y evitarla en aquellos con alto riesgo anesteacutesico Este hallazgo puede resultar de particular intereacutes en nuestra regioacuten

Resultados En 4284 en la VEDA se observoacute esofagitis que la histologiacutea caracterizoacute en leve y moderadasevera Esofagitis leve (EL) se observoacute en 31 y 11 presentaron esofagitis de moderada a severa (ES) En los canales distales la LB de IIM fue significativamente menor (P= lt005) en los pacientes con esofagitis en comparacioacuten con aquellos con mucosa normal Asi tambien al comparar las ES vs EL observando una p=0000Conclusiones En nintildeos la evaluacioacuten de la LB de IIM resulta un buen predictor de la integridad de la mucosa esofaacutegica Este meacutetodo ambulatorio y miacutenimamente invasivo permite una mejor seleccioacuten de nintildeos que requeriraacuten endoscopiacutea y evitarla en aquellos con alto riesgo anesteacutesico Este hallazgo puede resultar de particular intereacutes en nuestra regioacuten

Curr Gastroenterol Rep (2014) 16400PEDIATRIC GASTROENTEROLOGY (S ORENSTEIN SECTION EDITOR)

Combined Multichannel Intraluminal Impedance-pH (MII-pH)Multicenter Report of Normal Values from

117 Children

Hayat Mousa amp Rodrigo Machado amp Marina Orsi ampCatherine S Chao amp Tala Alhajj amp Mark Alhajj amp

Courtney Port amp Beth Skaggs amp Frederick W Woodley

H Mousa () R Machado T Alhajj M Alhajj B Skaggs F W WoodleyDivision of Pediatric Gastroenterology Nationwide ChildrenrsquosHospital 700 Childrenrsquos Drive JW 1985 Columbus OH USAC S Chao C PortInova Childrenrsquos Hospital Falls Church VA USAM OrsiThe Pediatric Gastroenterology Hepatology and Transplant UnitHospital Italiano Buenos Aires Argentina

Combined Multichannel Intraluminal Impedance-pH (MII-pH)Multicenter Report of Normal Values from 117 Children



bull Abstract bull Although combined multichannel intraluminal

impedanceesophageal pH monitoring (MII-pH) has replaced prolonged pH monitoring alone for assessing gastroesophageal reflux (GER) in the pediatric population it does so in the absence of reference values for non-acid GER (NAGER)

bull The purpose of this study was to identify a normal range of NAGER impedance values for infants and children

bull We evaluated EPMMII tracings for patients referred for GER assessment to Nationwide Childrenrsquos Hospital (Columbus OH) Inova Childrenrsquos Hospital and Hospital Italiano (Buenos Aires Argentina)

bull We excluded tracings from patients who had AGER indices greater than 50 of the upper end of normal (ie gt3 for children gt12 months and gt6 for infants le12 months) had a positive temporal association of GER with symptoms were on anti-reflux medications at the time of the study andor had a fundoplication prior to the study We also excluded studies with durations shorter than 20 h

bull Curr Gastroenterol Rep (2014) 16400




bull Values for NAGER percent time NAGER episode frequency frequency of proximal NAGER and mean NAGER duration were calculated for upright position recumbent and total

bull Study population consisted of 46 infants (20 female [F]26 male [M] median age 48 months [range 3 weeksndash119 months]) with a median AGER index of 22 (range 00ndash59 ) and 71 children (22 F49 M median age 72 years [range 13ndash17 years]) with a median AGER index of 11(range 0ndash30 ) Data are presented in tables in the text


bull The results of this study provide a range of values characteristic of infants and children with normal AGER indices and no positive temporal associations of GER with symptoms

bull These values may be used as references for comparison to identify infants andor children who may be at risk of developing serious clinical manifestations due to abnormal patterns of GER

bull Keywords Gastroesophageal reflux GER Non-acidGER NAGER AGER Impedance Normal values Reference values Symptom association probability

Curr Gastroenterol Rep (2014) 16400 46 Healthy infantsVariable Upright Recumbent Total

bull Percentage of AGER Median (IQR) 07 (03ndash13) 03 (01ndash08) 06 (03ndash09)bull 90th 18 11 11bull 95th 22 13 14bull AGER frequency Median (IQR) 10 (2ndash17) 8 (4ndash14) 20 (11ndash26)bull 90th 24 20 38bull 95th 33 24 48bull Number of proximal bull AGER episodes Median (IQR) 7 (0ndash14) 5 (2ndash10) 14 (4ndash22)bull 90th 23 15 37bull 95th 40 21 44bull Percentage of NAGER Median (IQR) 1 (06ndash16) 04 (01ndash11) 07 (05ndash12)bull 90th 27 17 18bull 95th 34 22 25bull NAGER frequency Median (IQR) 11 (6ndash20) 11 (2ndash23) 32 (16ndash45)bull 90th 39 44 58bull 95th 46 48 67

bull Number of proximalbull NAGER episodes Median (IQR) 8 (3ndash15) 8 (2ndash18) 22 (9ndash33)

90th 30 38 50bull 95th 46 40 57

NAGER frequency Median (IQR) 2 (1ndash8) 1 (0ndash5) 6 (3ndash11)bull 90th 17 9 20bull 95th 25 9 34bull Number of proximal bull NAGER episodes Median (IQR) 1 (0ndash6) 1 (0ndash2) 3 (1ndash7)bull 90th 10 5 13bull 95th 17 7 20bull Percentage of GER Median (IQR) 09 (04ndash19) 03 (01ndash05) 06 (03ndash12)bull 90th 3 08 18bull 95th 44 1 24bull GER frequency Median (IQR) 12 (5ndash28) 5 (2ndash12) 21 (11ndash41)bull 90th 56 17 65bull 95th 69 19 71bull Mean GER BCT (sec) Median (IQR) 14 (12ndash20) 14 (10ndash18) 15 (12ndash19)

Curr Gastroenterol Rep (2014) 16400 46 healthy infantsVariable Upright Recumbent Total

71 healthy childrenVariable Upright Recumbent Total


Curr Gastroenterol Rep (2014) 16400

71 healthy children

Variable Upright Recumbent Totalbull Number of proximalbull NAGER episodes Median (IQR) 1 (0ndash6) 1 (0ndash2) 3 (1ndash7)bull 90th 10 5 13bull 95th 17 7 20bull Percentage of GER Median (IQR) 09 (04ndash19) 03 (01ndash05) 06 (03ndash12)bull 90th 3 08 18bull 95th 44 1 24bull GER frequency Median (IQR) 12 (5ndash28) 5 (2ndash12) 21 (11ndash41)bull 90th 56 17 65bull 95th 69 19 71bull Mean GER BCT (sec) Median (IQR) 14 (12ndash20) 14 (10ndash18) 15 (12ndash19)bull 90th 27 28 25bull 95th 36 42 32


IIM-PH de 24 HS

VENTAJAS

Es ambulatorio

No requiere de complejidad

Pueden evaluarse los nintildeos bajo tratamiento con IBP

No requiere de anestesia

Es bien tolerado

Minimamente invasivo

El Consenso de ESPGHAN y NASPGHAN publicado en oct 2009 lo incluye dentro de las pruebas de dx

DESVENTAJAS

No hay valores de normalidad en pediatriacutea

Lleva tiempo el anaacutelisis de los datos

Las sondas son costosas

ConclusionesNO existe ninguna prueba diagnoacutestica uacutenica en el diagnoacutestico de la ERGE

La Impedanciometria Intraluminal Multicanal phmetria de 24 hs es una herramienta que suma informacioacuten de utilidad en el manejo cliacutenico

Por ser miacutenimamente invasiva que no requiere de complejidad puede realizarse en cualquier lugar del paiacutes y en toda Latinoamerica

A pesar del valor de las sondas y del tiempo que conlleva el anaacutelisis de los datos la informacioacuten que brinda contrabalancea favorablemente esto en pacientes complejos y particularmente en las presentaciones extraesofaacutegicas

iexcl Gracias por su atencioacuten

Nuacutemero de diapositiva 1

















Historia


Bibliografiacutea pHmetriacutea de 24 hs





Obituary The Death of the pH ProbeTHE JOURNAL OF PEDIATRICS December 2010- Vol 157 No 6e Philip E Putnam MD Cincinnati Childrenrsquos Hospital Medical Center Cincinnati Ohio











Combined multichannel intraluminal impedance-pH monitoring to selectpatients with persistent gastro-oesophageal reflux for laparoscopic NissenfundoplicationI Mainie 1 R Tutuian 1 A Agrawal 1 D Adams 2 D O Castell 1 1Division of Gastroenterology and Hepatology Medical University of South Carolina Charleston South CarolinaUSA 2Department of Surgery Medical University of South Carolina Charleston South Carolina USA

Combined MultiChannel Intraluminal Impedance and pH Esophageal Testing Compared to pH Alone for Diagnosing Both Acid and Weakly Acidic Gastroesophageal Reflux Hila A Agrawal A Castell DO Clinical Gastroenterology and Hepatology 2007 5 172-77






REVIEW Esophageal Impedance Monitoring forGastroesophageal RefluxHayat M Mousa yRachel Rosen Frederick W Woodley zMarina Orsi sectDaniela ArmasjjChristophe Faure John Fortunato Judith OrsquoConnor Beth Skaggs and ySamuel Nurko

REVISIOacuteNMonitoreo esofaacutegico por impedanciometriacutea para el reflujo gastroesofaacutegico


No particular sequence of events is observed in infants with ALTE and Gastroesophageal Reflux as measured by ImpedanceCohen Sabban J Fernandez Cuevas V Orsi M Donato G Busoni V DacuteAgostino D Pediatric Gastroenterology Unit Hospital Italiano-Buenos Aires-Argentina











Combined Multichannel Intraluminal Impedance-pH (MII-pH)Multicenter Report of Normal Values from 117 ChildrenHayat Mousa amp Rodrigo Machado amp Marina Orsi ampCatherine S Chao amp Tala Alhajj amp Mark Alhajj ampCourtney Port amp Beth Skaggs amp Frederick W Woodley




71 healthy children Variable Upright Recumbent Total





Hospital Italiano de Buenos AiresServicio de Gastroenterologiacutea y Hepatologiacutea Infantil

Centro de Trasplante Hepaacutetico-Intestinal Pediaacutetrico GRACIAS

Objetivos




Tiacutetulo


DIAGNOacuteSTICO











IIM-PH DE 24 HS






IIM-PH DE 24 HS

Entrada del Bolus

Salida del Bolus

Impe

danc

ia

Tiempo

Bolus Presente


Tragar Reflujo



Bolus Entry

Bolus Entry

Bolus Entry

Bolus Entry


Bolus Entry

Bolus Entry

Bolus Entry

Bolus Entry

Bolus Entry























Reflujo No Acido

RESULTADOS

9


3 cm

5 cm

7 cm

9 cm

11 cm

13 cm

pH ndash 3 cm


1 pH channel

16

True GER Episode



17


pH Remains Below 40

Acid ReReflux

Historia































1ordf pH

2ordf pH

3ordf pH

IR282

IR69

IR18

A


pnea












IIM-PH de 24 HS

pH

IIM














































































INTRODUCCIOacuteN







Linea basal













117 Children

























90th 30 38 50bull 95th 46 40 57






71 healthy children



IIM-PH de 24 HS

VENTAJAS

Es ambulatorio




Es bien tolerado



DESVENTAJAS


























Historia
















































Objetivos




Tiacutetulo


DIAGNOacuteSTICO











IIM-PH DE 24 HS






IIM-PH DE 24 HS

Entrada del Bolus

Salida del Bolus

Impe

danc

ia

Tiempo

Bolus Presente


Tragar Reflujo



Bolus Entry

Bolus Entry

Bolus Entry

Bolus Entry


Bolus Entry

Bolus Entry

Bolus Entry

Bolus Entry

Bolus Entry























Reflujo No Acido

RESULTADOS

9


3 cm

5 cm

7 cm

9 cm

11 cm

13 cm

pH ndash 3 cm


1 pH channel

16

True GER Episode



17


pH Remains Below 40

Acid ReReflux

Historia































1ordf pH

2ordf pH

3ordf pH

IR282

IR69

IR18

A


pnea












IIM-PH de 24 HS

pH

IIM














































































INTRODUCCIOacuteN







Linea basal













117 Children

























90th 30 38 50bull 95th 46 40 57






71 healthy children



IIM-PH de 24 HS

VENTAJAS

Es ambulatorio




Es bien tolerado



DESVENTAJAS


























Historia
















































Tiacutetulo


DIAGNOacuteSTICO











IIM-PH DE 24 HS






IIM-PH DE 24 HS

Entrada del Bolus

Salida del Bolus

Impe

danc

ia

Tiempo

Bolus Presente


Tragar Reflujo



Bolus Entry

Bolus Entry

Bolus Entry

Bolus Entry


Bolus Entry

Bolus Entry

Bolus Entry

Bolus Entry

Bolus Entry























Reflujo No Acido

RESULTADOS

9


3 cm

5 cm

7 cm

9 cm

11 cm

13 cm

pH ndash 3 cm


1 pH channel

16

True GER Episode



17


pH Remains Below 40

Acid ReReflux

Historia































1ordf pH

2ordf pH

3ordf pH

IR282

IR69

IR18

A


pnea












IIM-PH de 24 HS

pH

IIM














































































INTRODUCCIOacuteN







Linea basal













117 Children

























90th 30 38 50bull 95th 46 40 57






71 healthy children



IIM-PH de 24 HS

VENTAJAS

Es ambulatorio




Es bien tolerado



DESVENTAJAS


























Historia


























































IIM-PH DE 24 HS






IIM-PH DE 24 HS

Entrada del Bolus

Salida del Bolus

Impe

danc

ia

Tiempo

Bolus Presente


Tragar Reflujo



Bolus Entry

Bolus Entry

Bolus Entry

Bolus Entry


Bolus Entry

Bolus Entry

Bolus Entry

Bolus Entry

Bolus Entry























Reflujo No Acido

RESULTADOS

9


3 cm

5 cm

7 cm

9 cm

11 cm

13 cm

pH ndash 3 cm


1 pH channel

16

True GER Episode



17


pH Remains Below 40

Acid ReReflux

Historia































1ordf pH

2ordf pH

3ordf pH

IR282

IR69

IR18

A


pnea












IIM-PH de 24 HS

pH

IIM














































































INTRODUCCIOacuteN







Linea basal













117 Children

























90th 30 38 50bull 95th 46 40 57






71 healthy children



IIM-PH de 24 HS

VENTAJAS

Es ambulatorio




Es bien tolerado



DESVENTAJAS


























Historia
















































IIM-PH DE 24 HS

Entrada del Bolus

Salida del Bolus

Impe

danc

ia

Tiempo

Bolus Presente


Tragar Reflujo



Bolus Entry

Bolus Entry

Bolus Entry

Bolus Entry


Bolus Entry

Bolus Entry

Bolus Entry

Bolus Entry

Bolus Entry























Reflujo No Acido

RESULTADOS

9


3 cm

5 cm

7 cm

9 cm

11 cm

13 cm

pH ndash 3 cm


1 pH channel

16

True GER Episode



17


pH Remains Below 40

Acid ReReflux

Historia































1ordf pH

2ordf pH

3ordf pH

IR282

IR69

IR18

A


pnea












IIM-PH de 24 HS

pH

IIM














































































INTRODUCCIOacuteN







Linea basal













117 Children

























90th 30 38 50bull 95th 46 40 57






71 healthy children



IIM-PH de 24 HS

VENTAJAS

Es ambulatorio




Es bien tolerado



DESVENTAJAS


























Historia

















































Tragar Reflujo



Bolus Entry

Bolus Entry

Bolus Entry

Bolus Entry


Bolus Entry

Bolus Entry

Bolus Entry

Bolus Entry

Bolus Entry























Reflujo No Acido

RESULTADOS

9


3 cm

5 cm

7 cm

9 cm

11 cm

13 cm

pH ndash 3 cm


1 pH channel

16

True GER Episode



17


pH Remains Below 40

Acid ReReflux

Historia































1ordf pH

2ordf pH

3ordf pH

IR282

IR69

IR18

A


pnea












IIM-PH de 24 HS

pH

IIM














































































INTRODUCCIOacuteN







Linea basal













117 Children

























90th 30 38 50bull 95th 46 40 57






71 healthy children



IIM-PH de 24 HS

VENTAJAS

Es ambulatorio




Es bien tolerado



DESVENTAJAS


























Historia





































































Reflujo No Acido

RESULTADOS

9


3 cm

5 cm

7 cm

9 cm

11 cm

13 cm

pH ndash 3 cm


1 pH channel

16

True GER Episode



17


pH Remains Below 40

Acid ReReflux

Historia































1ordf pH

2ordf pH

3ordf pH

IR282

IR69

IR18

A


pnea












IIM-PH de 24 HS

pH

IIM














































































INTRODUCCIOacuteN







Linea basal













117 Children

























90th 30 38 50bull 95th 46 40 57






71 healthy children



IIM-PH de 24 HS

VENTAJAS

Es ambulatorio




Es bien tolerado



DESVENTAJAS


























Historia
















































RESULTADOS

9


3 cm

5 cm

7 cm

9 cm

11 cm

13 cm

pH ndash 3 cm


1 pH channel

16

True GER Episode



17


pH Remains Below 40

Acid ReReflux

Historia































1ordf pH

2ordf pH

3ordf pH

IR282

IR69

IR18

A


pnea












IIM-PH de 24 HS

pH

IIM














































































INTRODUCCIOacuteN







Linea basal













117 Children

























90th 30 38 50bull 95th 46 40 57






71 healthy children



IIM-PH de 24 HS

VENTAJAS

Es ambulatorio




Es bien tolerado



DESVENTAJAS


























Historia
















































16

True GER Episode



17


pH Remains Below 40

Acid ReReflux

Historia































1ordf pH

2ordf pH

3ordf pH

IR282

IR69

IR18

A


pnea












IIM-PH de 24 HS

pH

IIM














































































INTRODUCCIOacuteN







Linea basal













117 Children

























90th 30 38 50bull 95th 46 40 57






71 healthy children



IIM-PH de 24 HS

VENTAJAS

Es ambulatorio




Es bien tolerado



DESVENTAJAS


























Historia
















































17


pH Remains Below 40

Acid ReReflux

Historia































1ordf pH

2ordf pH

3ordf pH

IR282

IR69

IR18

A


pnea












IIM-PH de 24 HS

pH

IIM














































































INTRODUCCIOacuteN







Linea basal













117 Children

























90th 30 38 50bull 95th 46 40 57






71 healthy children



IIM-PH de 24 HS

VENTAJAS

Es ambulatorio




Es bien tolerado



DESVENTAJAS


























Historia
















































Historia































1ordf pH

2ordf pH

3ordf pH

IR282

IR69

IR18

A


pnea












IIM-PH de 24 HS

pH

IIM














































































INTRODUCCIOacuteN







Linea basal













117 Children

























90th 30 38 50bull 95th 46 40 57






71 healthy children



IIM-PH de 24 HS

VENTAJAS

Es ambulatorio




Es bien tolerado



DESVENTAJAS


























Historia










































































1ordf pH

2ordf pH

3ordf pH

IR282

IR69

IR18

A


pnea












IIM-PH de 24 HS

pH

IIM














































































INTRODUCCIOacuteN







Linea basal













117 Children

























90th 30 38 50bull 95th 46 40 57






71 healthy children



IIM-PH de 24 HS

VENTAJAS

Es ambulatorio




Es bien tolerado



DESVENTAJAS


























Historia

















































pnea












IIM-PH de 24 HS

pH

IIM














































































INTRODUCCIOacuteN







Linea basal













117 Children

























90th 30 38 50bull 95th 46 40 57






71 healthy children



IIM-PH de 24 HS

VENTAJAS

Es ambulatorio




Es bien tolerado



DESVENTAJAS


























Historia



























































IIM-PH de 24 HS

pH

IIM














































































INTRODUCCIOacuteN







Linea basal













117 Children

























90th 30 38 50bull 95th 46 40 57






71 healthy children



IIM-PH de 24 HS

VENTAJAS

Es ambulatorio




Es bien tolerado



DESVENTAJAS


























Historia





























































































































INTRODUCCIOacuteN







Linea basal













117 Children

























90th 30 38 50bull 95th 46 40 57






71 healthy children



IIM-PH de 24 HS

VENTAJAS

Es ambulatorio




Es bien tolerado



DESVENTAJAS


























Historia




















































Linea basal













117 Children

























90th 30 38 50bull 95th 46 40 57






71 healthy children



IIM-PH de 24 HS

VENTAJAS

Es ambulatorio




Es bien tolerado



DESVENTAJAS


























Historia




























































117 Children

























90th 30 38 50bull 95th 46 40 57






71 healthy children



IIM-PH de 24 HS

VENTAJAS

Es ambulatorio




Es bien tolerado



DESVENTAJAS


























Historia





































































90th 30 38 50bull 95th 46 40 57






71 healthy children



IIM-PH de 24 HS

VENTAJAS

Es ambulatorio




Es bien tolerado



DESVENTAJAS


























Historia



















































71 healthy children



IIM-PH de 24 HS

VENTAJAS

Es ambulatorio




Es bien tolerado



DESVENTAJAS


























Historia
















































IIM-PH de 24 HS

VENTAJAS

Es ambulatorio




Es bien tolerado



DESVENTAJAS


























Historia






































































Historia
















































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