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MedicalandSurgicalTreatmentsforShortBowelSyndrome
DouglasL.Seidner,M.D.VanderbiltUniversityMedicalCenter
CenterforHumanNutriHon
Disclosures
• ShirePharmaceuHcals:Consultant
• ZealandPharmaA/S:Consultant
• VanderbiltOpHonCareInfusion:MedDir.DiscussionofofflabeluseofmedicaHonwillbenoted.
LearningObjecHves
• ReviewkeyconceptstohelpunderstandthetreatmentofSBS
• DiscusstheindicaHons,mechanismofacHon,andsideeffectofmedicaHonsusedforSBS
• UnderstandtheroleofsurgeryinthemanagementofSBS
PathwaytoEnteralAutonomyinShortBowelSyndrome
Bowel Resection
* Intestinal Rehabilitation
Short Term TPN Long Term TPN
*Diet modification, enteral supplements, medications, intestinal trophic factors
Bowel Transplant
Autologous GI Reconstruction
GoalsofIRProgram/Process
• RepletenutriHondeficiencies• ControldiarrheaandmaintainhydraHon• PromoteenteralautonomybyopHmizingabsorpHvefuncHon– DietandfluidmodificaHon– MedicaHonsforGIdiseaseandsymptoms– SurgicalintervenHon
• TreatandpreventcomplicaHons• Improvequalityoflife
ShortBowelSyndrome
• SevereintesHnalmalabsorpHonthatoccursaZerextensivesmallbowelresecHon
• Clinicalfeaturesincludediarrhea,dehydraHon,electrolyteabnormaliHes,andmalnutriHon
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NormalAdultGIAnatomyandSBS
SBlength:365-600cm
Duodenum:~30cm
Jejunum:~150to200cm
Ileum:~200to300cm
Colon:~150cm
ShortBowelSyndrome<200cmofjejunum-ileum(distaltotheLigamentofTreitz)
ShortBowelSyndromeMechanismsofMalabsorpHon
GastricAcidHypersecreHon
• CommonaZerextensiveSBresecHon• Transient,lasHng<4-6mo• Pathogenesis:Hypergastrinemia• Consequences– PepHculceraHon– InacHvaHonofpancreaHcenzymes– PrecipitaHonofbilesalts– Metabolicalkalosisandhypokalemia
GastricAnHsecretoryMedicaHons
• ProtonPumpInhibitor– Esomeprazole,lansoprazole,omeprazole,pantoprazole,rabeprazole
– Sideeffects:Abdominalpain,diarrhea,nausea,headache
• Histamine-2receptorantagonists– CimeHdine,famoHdine,nizaHdineraniHdine– Sideeffects:Diarrhea,consHpaHon,abdominalpain,headache,gynecomasHa(cimeHdine),hepaHHs,lowplatelets
GIAnHsecretoryMedicaHons*
• SomatostaHnanalogue– OctreoHde(inhibitsGH,glucagon,insulinandothers)– MayinterferewithintesHnaladaptaHon– Sideeffects:Abdominalpain,diarrhea,nausea,headache,dysrhythmias,hyper/hypoglycemia,hypothyroidism,gallstones
• Alpha-2adrenergicreceptoragonist– Clonidine– Sideeffects:Hypotension,drymouth,abdominalpain,confusion,sleepdisorder,rash
*Offlabel
RapidGastrointesHnalTransit
• ExtensiveSBresecHon;ileum&colon• LossofneuroendocrinecellsthatsecretePYY,GLP-1,GLP-2andotherfactors
• Absenceofileocecalvalve• Consequences– Rapidgastricemptying– DecreasedintesHnaltransitHme– IncreasedgastricsecreHons
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AnHdiarrhealMedicaHonsMedicaNon Onedose StarNngdose Maxdose
Loperamide(Imodium)
2mg(5mL) 1to2tablets(5to10mL)POQID
8tablets(40mL)/d
Diphenoxylate(LomoNl)
2.5mg(5mL) 1to2tablets(5to10mL)POQID
8tablets(40mL)/d
CodeineelixirTylenol#3
15mL15,30,60mg
15to30mLPOQID15mgPOQID
180mL/d360mg/d
OpiumTincture 0.3mL(6drops) 6to20drops(0.3to1mL)POQID
120drops(6mL)/d
AnHdiarrhealmedsaremosteffecHveif½hrto1hrbeforemeals
AnHdiarrhealMedicaHons
• Sideeffects:– Abdominalpain,distenHon,nausea,vomiHng– SedaHon,dizziness– AnHcholinergic(combinedwithdiphenoxylatetodiscourageabuse):xerostomia,tachycardia,mydriasis
SmallIntesHnalBacterialOvergrowth
• Uncommonunless…– Blindloop,stricture,internalfistula– IncreasedintesHnaltransit– Decreasedgastricacid,pancreaHcsecreHons– Absenceofileocecalvalve
• Consequences– Bacteriaconsumeluminalnutrients– Mucosalinjury– D-lacHcacidosis
SIBOManagement
• SurgicalintervenHon• LimitanHsecretoryandanHdiarrhealmeds• ProbioHcs(overthecounter)• AnHbioHcs(offlabel)–7daycourse– Amox/Clavulanate500/125mgpoHd,#21,$63– Metronidazole250mgpoHd,#21,$24– Rifaximin550mgpobid,#14,$$$$$
Quigley,E.InfectDisClinNAm2010;24:943
OtherMedicaHonsandSupplements
• Bileacidtherapy– Cholestyramine,colesHpol– Cholylsarcosine(NAinUS)– Oxbile(overthecounter)
• PancreaHcEnzymeReplacementTherapy
HeydornSetal.ScanJGastroenterol1999:34;818Liple,KH.DigDisSci1992;37(6):929
Glucagon-LikePepHde2(GLP-2)&TedugluHde(TED)
• SHmulatescryptcellproliferaHon,inhibitsenterocyteapoptosis
• Increasesvillusheight/cryptdepth• IncreasesnutrienttransporteracHvity• IncreasesintesHnalbloodflow• InhibitsgastricacidsecreHonandmoHlity
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TedugluHdePivotalTrials
• Two24wkinternaHonalrandomizeddouble-blindplacebocontrolledtrialsin83and86adults– Parenteralsupport>12months• 004trial:2:2:1-0.05mg/kg/dvs.0.10mg/kg/dvs.PBO• STEPStrial:1:1-0.05mg/kg/dvs.PBO
– Primaryend-point=PSreducHonwasmetforbothtrials0.05gm/kg/d
JeppesenPB,Gut2011;60:902-914JeppesenPB,Gastroenterology2012;143:1473-81
FDARegulaHonofTedugluHde• REMS:RiskEvaluaHonandMiHgaHonStrategy– ImposedbyFDAtoensurethatbenefits>risks– Risks/precauHons:• NeoplasHcgrowth• IntesHnalobstrucHon• BiliaryandpancreaHcdisease• Fluidoverload• IncreasedabsorpHonofconcomitantoralmedicaHon• AdverseReacHons(>10%-n/v/abdominalpaindisteHon,URIsymptoms,HA,injecHonsite,fluidoverload)
hpps://www.gapex.com/hcp/rems.aspx
Prescribingandregulatoryissues
• IndicaHon:AdultpaHentwithSBSonPS*• DuraHonofPSisnotmenHoned
• Prescribersmustpassanonlinecourse^• Dispensedby5infusioncompanies^• MaintainSBSregistry^(NCT01990040)• Casemanagementsupportfromcompanytoassistwithdrugcost
^FDAREMS*PrescribinginformaHonfrompackageinsert
MedicaHonsforSBSIndicaNon MedicaNon
GastricacidhypersecreHon Protonpumpinhibitor
Histamine-2ReceptorAntagonist
GIsecreHon SomatostaHnanalogue*^
Alpha-2adrenergicreceptoragonist*
Diarrhea Opioidagonist
SmallIntesHnalBacterialOvergrowth ProbioHcs#/AnHbioHcs*
Bileaciddiarrhea Bileacidbindingresin
Bileaciddeficiency Bilesaltreplacement#
PancreaHcenzymedeficiency PancreaHcenzymereplacement
Parenteralsupportdependent GLP-2analogue
*Offlabel#Overthecounter^MayinhibitadaptaHon
SurgicalManagementofShortBowelSyndrome
• AutologousGIReconstrucHon– RestoreintesHnalconHnuity
– Strictureplasty
SerialTransverseEnteroplasty
LongitudeIntesHnalLengtheningandTailoring
ReversedSegment
SurgicalManagementofShortBowelSyndrome
PlicaHon
Valve
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IntesHnalTransplantaHonforSBS
a. SmallIntesHneb. Liver–SmallIntesHnec. MulHvisceral(aboveplusstomachandpancreas)
IntesHnalTransplantaHonforSBS
• FailureofHPN(alsoCMSindicaHonsforIT)– Impending(bilirubin3-6mg/dL)orovertliverfailurefromPN– Thrombosisof>2centralveins– TwoormoreepisodesCRBSI/yrofsystemicsepsis,oneepisodeof
fungemia,sepHcshock,ARDS– FrequentepisodesofseveredehydraHon
• Highriskofdeath– Invasiveintra-abdominaldesmoidtumor– SevereSBS:gastroorduodenostomy,<20cmSBinadults(10cminfant)
• HighmorbidityorpooracceptanceofHPN– FrequenthospitalizaHon,narcoHcdependency,unabletofuncHon
(pseudoobstrucHon,highstomaoutput)– PaHent’sunwillingnesstoacceptlong-termHPN.
IntesHnalFailurewith
PironiL,ArendsJ,BozzexF,etal.ClinNutr2016;35:247(recommendlisHngforTx)
IntesHnalTransplantaHonforSBS
GraZSurvival
TransplantVolume
GrantD,etal.AmJTranspl2015;15:210
ManagementofChronicIF-SBS
Diet-Hyperphagia
SurgeryMedicaHon
PaHentIntesHnalRehabilitaHon
References1. KumpfVJ.PharmacologicmanagementofdiarrheainpaHentswithshortbowel
syndrome.JPENJParenterEnteralNutr2014;38(suppl1):38S-44S.2. JeppesenPB.PharmacologicOpHonsforIntesHnalRehabilitaHoninPaHentswith
ShortBowelSyndrome.JPENJParenterEnteralNutr2014;38:45S-52S.3. SchwartzLK,O'KeefeSJD,FujiokaK,etal.Long-termTedugluHdeforthe
treatmentofpaHentswithintesHnalfailureassociatedwithshortbowelsyndrome.ClinicalandtranslaHonalgastroenterology2016;7:e142.
4. Seidner,DL,Schwartz,LK,Winkler,MF,etal.IncreasedintesHnalabsorpHonintheeraoftedugluHdeanditsimpactonmanagementstrategiesinpaHentswithshortbowelsyndrome-associatedintesHnalfailure.JPENJParenterEnteralNutr2013;37:201-11.
5. PironiL,ArendsJ,BozzexF,etal.ESPENguidelinesonchronicintesHnalfailureinadults.ClinNutr2016;35:247-307.
6. GrantD,Abu-ElmagdK,MazariegosG,etal.IntesHnalTransplantRegistryReport:GlobalAcHvityandTrendsAmJTranspl2015;15:210–19.