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Intestinal Rehabilitation & Surgical Management

Lauren K. Schwartz, MD

Concorde Medical Group

June 12, 2015

Financial Disclosures

NPS Pharmaceuticals

Member of scientific steering committee

Coram Home Care

Advisory board member

Overview Overview of SBS

Normal gut physiology 

Short bowel pathophysiology

Intestinal rehabilitation

Evaluation for therapeutic planning

Traditional interventions

New trophic therapy 

Intestinal transplant

Indications, Operations, Expectations 

Short Bowel Syndrome Malabsorptive condition caused by loss of an extensive length of small intestine 

<200 cm of post duodenal small bowel 

Manifestations

Diarrhea

Dehydration, electrolyte derangements

Weight loss        Malnutrition

Gastro 2006;130:S3-4

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SBS: EtiologiesAdults

Mesenteric  ischemia

Crohn’s disease

Radiation enteritis

Trauma

Recurrent obstruction

Volvulus

Internal hernia

Children Necrotizing enterocolitis

Intestinal atresia

Volvulus

Extensive agangliosis

Gastroschisis

Congenital short bowel

Meconium peritonitis

The Healthy Intestine Small bowel: 6 meters (3‐8 m) or 20 feet

Colon: 1.5 meters or 5 feet

Duodenum 25 cm

Jejunum 2.5 m

Ileum 3.5 m

The Healthy IntestineAbsorption=8.8 L

Ingestion2000 mL/d water

Bile1000 mL/d

Intestinal secretions1000 mL/d

Small intestinal absorption 7500 mL/d

Ingestion + secretion=9 L

Colon absorption1000–3000 mL/d

Saliva 1000 mL/d

Gastric secretions2000 mL/d

Pancreatic secretions2000 mL/d

Fluid Secretion and Absorption

150-200 mL/d water excreted

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The Shortened Intestine

End-JejunostomyJejunocolic anastomosis

Jejunoileal anastomosis

Prognosis declines

Retained bowel

Jejunum

The Shortened Intestine Retained bowel anatomy determines functional capacity and PN dependence

Length of small bowel remaining

Presence of IC valve and colon

Type of small bowel (jejunum vs. ileum)

Health of residual bowel

Messing B et al. Gastroenterology 1999; 117

PN D

epen

den

cy Probab

ility (%

)

Years following final digestive circuit modification

Bowel Length and PN Dependence

0‐49 cm

50‐99 cm

100‐150 cm

The Shortened Intestine Minimal small bowel lengths separating need for transient vs. permanent TPN

Messing B et al. Gastroenterology 1999; 117

Intestinal Circuit Small bowel length

End enterostomy 100 cm

Jejunocolic 65 cm

Jejunoileocolic 30 cm

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Intestinal Adaptation Functional changes

Slowed transit

Increased transporters

Structural changes

Dilation, lengthening

Increased villous height, diameter

SBS: Treatment Options

Intestinal Rehab

Intestinal

Transplant

Long-term TPN

Surgical

Augmentation

Intestinal Rehabilitation The process of restoring nutritional status and intestinal function with ultimate goal of TPN withdrawal Optimize nutritional status

Control diarrheal losses 

Enhance absorption

Wean TPN

Rehab modalities Diet, TPN, EN 

Pharmacotherapy

Growth factors

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Malabsorption

Com

pens

ator

y

Flu

id o

r N

utrit

iona

l Sup

port

Intestinal insufficiency

Intestinal failure

Additional oral intake (hyperphagia)

Parenteral support

Spectrum of Short Bowel Syndrome

Heterogeneous population

• Anatomy and bowel function

• Ability to compensate orally for malabsorption

• Symptom severity

Initial Evaluation

Residual Anatomy

Intestinal lossesFluid balance

Nutritional Status

Surgical historyOperative recordsBowel disease

Ostomy, fistula, tubes

Small bowel series +/‐ barium enemaCT enterographyEGD/Colonoscopy

Diarrheal frequencyOstomy outputDrain/fistula outputIntravenous fluids

OrthostaticsOstomy, drains, fistula

Electrolytes, BUN/Cr24 hour I/OsUrine Na, sp gravity48‐72 hr fecal fat

Weight lossDietary intakeTube feeds or TPNTPN complication

Weight, height, BMIMuscle/fat wastingSkin or hair changes 

Vit/min levelsAlbumin/prealbuminD‐xylose, fecal fat

Histo

ryExam

Testing

Treatment ApproachPost resectional stabilization

Intestinal transplantation

Intestinal rehabilitation

Surgical augmentation

DietEN/TPN

Antidiarrheals

PPI, H2RA

PancrelipaseBile acid resin

Antibiotics

GH, GLP‐2

Restore continuity

Reverse segment

Bianchi 

STEP

TPN weaningComplete/Partial/None

Line Infection

Liver disease

Loss of access

Diet Modification Meal pattern

5 to 6 small, calorically‐dense meals

Separate liquids and solid

Meal composition Restrict simple sugars

Restrict insoluble fiber

Fluid choice = ORS

Translating guidelines into daily diet requires help from a knowledgeable dietician

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Diet ModificationColon Present Colon Absent

CHO 50–60%

PRO 20%

FAT 20–30%

Avoid oxalates

Isotonic/hypoosmolar fluids

Soluble fiber 5–10 g/day

Lactose as tolerated

CHO 40–50%

PRO 20%

FAT 30–40%

Oxalates: no restriction

Isotonic, high Na fluids

Soluble fiber 5–10 g/day

Lactose as tolerated

More complex carbs, less fat More fat, less carbs

Oral Rehydration Solutions

Composition

Na: 70‐90 mMol/L

Sugar: 20 g/L

Avoid hypotonic fluids

Sip, don’t guzzle

Oral Rehydration SolutionsCHOg/L

NA+ mEq/L

K+ mEq/L

HCO3 mEq/L

OsmomOsm/L

WHO ORS 

Standard Formula  20 90 20 30 310

Reduced‐Osmolality Formula  13.5 75 20 30 245

Rehydration Solutions

CeraLyte 70 (Cera Products)  40 70 20 30 235

CeraLyte 90 (Cera Products)  40 90 20 30 260

Equalyte (Ross)  30 78 22 30 305

Jianas Brothers ORS  20 90 20 10 300

Liquilyte (Gerber)  25 45 20 30 250

Pedialyte (Ross)  25 45 20 30 300

Rehydralyte (Ross)  25 75 20 30 300

Sports Drink 

Gatorade 60 20 3 340

G2 + ½ tsp salt 29 63 3 254

Oral vitamin/mineral supplementsNutrient Strength Dose

Vitamin A‐D‐E 25,000 IU of A1,000 IU of D400 IU of E

1 tablet PO daily

Calcium citrate 500–600 mg tablet 1 to 2 tablets PO TID

Magnesium lactateMagnesium gluconate

84 mg tablet1000 mg tab (or liquid)

1 to 2 tablets PO TID1 to 3 tablets PO TID

Potassium chloride 20 mg tablet 1 to 2 tablets PO daily

Phos (KPhosNeutral)Sodium bicarbonate

250 mg tablet650 mg tablet

1 tablet PO TID1 tablet PO TID

Chromium 100 µg tablet 1 to 2 tablets PO TID

CopperSelenium

3 mg tablet200 mcg tablets

1 to 2 tablets PO daily1 tablet PO daily

Zinc sulfate 220 mg tablet 1 to 3 tablets PO daily

Matarese et al. J Clin Gastroenterol. 2006;40(Suppl 2):S85-89.

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Intestinal Rehab: MedicationsAntidiarrheals: 

Imodium, Lomotil, DTO, Codeine

Octreotide

Acid suppression: PPI, H2RA

Clonidine

Bile acid resins:cholestyramine

Pancreatic enzymes

Cyclical antibiotics

Antidiarrheals

Medication Max Dose

Loperamide (Imodium®) 4 mg QID

Diphenoxylate/atropine (Lomotil®) 2 tabs QID

Tincture of opium 20 drops QID

Codeine 60 mg QID

Benefits of opiate‐based antidiarrheals in pts with high output jejunostomy questionable; more effective in pts with colon 

Antisecretory Agents H2RA and PPI 1,2

Reduces intestinal output

Controls acid excess after major resection

Limits pancreatic enzyme denaturation, PUD

Octreotide 3

+ Improves fluid balance, decreases IVF needs

‐ Suppresses gut hormone levels in blood; could negatively affect adaptation

‐ Promotes cholestasis, gallstones

Clonidine 4

Reduces fluid, sodium losses1 Jeppesen PB, et al. Gut. 1998;6:763-769.

2 Nightingale B, et al Alment Pharmacol Ther. 1991;5:405-12

3 O’Keefe SJD, et al. JPEN. 1994; 18:26-34.4 Buchman et al. JPEN 2006;30:487-491.

Antisecretory Agents H2RA and PPI 1,2                    Start after major resection

Reduces intestinal output

Controls acid excess after major resection

Limits pancreatic enzyme denaturation, PUD

Octreotide 3 Avoid most of the time

+ Improves fluid balance, decreases IVF needs

‐ Suppresses gut hormone levels in blood; could negatively affect adaptation

‐ Promotes cholestasis, gallstones

Clonidine 4 Use in select cases (hypertension)

Reduces fluid, sodium losses1 Jeppesen PB, et al. Gut. 1998;6:763-769.

2 Nightingale B, et al Alment Pharmacol Ther. 1991;5:405-12

3 O’Keefe SJD, et al. JPEN. 1994; 18:26-34.4 Buchman et al. JPEN 2006;30:487-491.

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Adjunctive Medications Pancreatic Enzymes

Dose 500‐1000 lipase units/kg per meal

Coated: Creon, Zenpep. Ultrase

Uncoated: Viokace

Bile acid resins Useful if colon present and 

suspect choleretic diarrhea

Antibiotics for SIBO

Intestinal Trophic Hormones Two hormones have been studied for their trophic effects on the intestine

Growth Hormone

Glucagon‐like peptide 2 (GLP‐2)

Rationale: Promote bowel adaptation to enhance absorptive capacity

Adaptation/Hyperadaptation

Resection1 year

Bow

el F

unct

ion

2 years 3 years

Early treatment Late treatment

Accelerated

Spontaneous adaptation

GLP‐2 Analog: Teduglutide

• GLP‐2 is a hormone normally secreted by L‐cells of the  ileum and colon

• Effects on adaptation

• Teduglutide (Gattex) is a modified form of GLP‐2 with single amino acid substitution that increases half‐life 

Cellular Physiologic

• villous height• crypt depth

• Intestinal blood flow• Improved fluid absorption• Improved nutrient absorption

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STEPS Study Design

Jeppesen PB, et al. Gastroenterology 2012;43:1473-81

Stage 1≤17 weeks

Stage 224 weeks

Screening

1–7 days

PS optimization

PS stabilization

Teduglutide 0.05 mg/kg/day s.c. (n=43)

Placebo(n=43)

4–8 weeks24 weeks

0–8 weeks

Week 2 4 6 8

• 48 hours prior to each visit, patients recorded their oral fluid intake and urine production

• PS reductions (up to 30%) if urine volume >10% higher than baseline

Urine volume 1–2 L/day

1 2 4 8 12 16 20 24Baseline

Follow‐up

Randomization

Optimized PS reductions

STEPS 020: Responder Analysis

(n=27/43)

(n=13/43)30%

Response is defined as 20–100% Reduction in weekly PN/IV volume at weeks 20 & 24

Jeppesen PB, et al. Gastroenterology 2001;43: 1473-81

STEPS: Mean Reduction in PN Volume

‐0.5‐1.0

‐1.5‐1.9 ‐2.1 ‐2.3

‐1.1

‐2.0*

‐2.9**‐3.4***

‐3.8***

‐4.4***

Difference2.1 L/week

Mean

 chan

ge in

 PS volume (L/week)

Week

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Intestinal Transplant: History

1960’s 1990’s1980’s1970s

ITx first attempted

Deaths due to technical complications, rejection, infection

CSA (’78) 1st successful ITx

1988: Grant et al. adult combined liver/SB tx

Tacrolimus (’90)

Growth in # of transplants

2000’s

# of ITx

US 3/20132,287 Itx

CMS recognizes ITx 2000

Intestinal Transplant: Indications Irreversible intestinal failure with TPN dependence 

TPN failure* PLUS

Blood stream infections

Liver dysfunction

Loss of vascular access

Recurrent dehydration despite TPN/IVF

1 fungemia

1 line sepsis with shock or ARDS

Metastatic infection

≥2 line sepsis w/ hospitalization in a yr

* As defined by Center for Medicare and Medicaid Services

Impending or overt liver failure

Thrombosis of ≥2 central veins

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Intestinal Transplant: Timing Is there a role for pre‐emptive intestinal transplant?

Can we predict TPN failure?

Messing B et al. Gastroenterology 1999; 117

Severe clinical disease

Severe histologic disease

Cavicchi et l. Ann Intern Med 2000;132

Pro

babi

lity

of B

eing

Fre

e of

Liv

er D

isea

se

Months

Sur

viva

l Pro

babi

lity

Years post bowel resection

Intestinal Transplant: Procedures

Isolated ITx Liver-ITx

Images from Uptodate.com 2013

Multivisceral Tx•Small bowel +/- colon •Small bowel +/- colon

•Liver

•Small bowel +/- colon

•Liver

•Stomach, duodenum, pancreas

Transplant 1-Year 5-Year 10-Year

Liver 86 68 53

Intestine 75 55 27

Intestinal Transplant: Survival

% Graft Survival 

Transplant 1-Year 5-Year 10-Year

Liver 89 74 60

Intestine 79 63 38

% Patient Survival

SRTR DataSRTR Data

Transplant vs. TPN: SurvivalHome TPN Intestinal Transplant$

All patients*

1 year: 87‐96%

3 year: 70‐90%

Short bowel patients+

5 year:

93% length 100‐150 cm

79% length 50‐99 cm

57% length <50 cm

Patient survival

1 year:  79%

3 year:  66%

5 year:  63%

*Howard L. Gastro 1995;109:355+Messing B. Gastroenterology 1999; 117

$SRTR Data

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Conclusions: Short bowel syndrome is a complex condition requiring coordinated care between gastroenterologist, surgeon, and nutrition expert

Approach to intestinal rehab must be tailored to the individual patient, taking into account residual bowel anatomy

The goals of intestinal rehab are restoration of enteral autonomy and withdrawal of PN and IVF support

Should lead to reduced complications, elimination of need for transplant, improved quality of life

Conclusions: We are entering a new era of intestinal failure management with the availability of intestinal trophic hormones  Promises to advance our ability to reduce PN dependence

When TPN withdrawal is not possible and patients experience major complications, referral for intestinal transplant is appropriate

Consider early referral to a transplant/intestinal rehab center for:

Baseline assessment 

Extreme short bowel syndrome

Non‐transplant surgery (restore continuity, bowel lengthening, complex fistula repair)

Question A 32 year‐old woman with a history of Crohn’s disease and multiple related surgeries presents to you for management of a high output ileostomy.  Her last surgery was 6 months ago, and resulted in a residual small bowel length of 180 cm.  She is TPN dependent. All of the following are appropriate recommendations except:

Encourage hydration with oral rehydration solutions

Add IV famotidine to her TPN

Start cholestyramine twice daily

Start tincture of opium 30 minutes pre‐meals

Question A 44 year‐old woman with a history of roux‐en Y gastric bypass for obesity develops ischemic bowel due to an internal hernia.  Her post op anatomy consists of 100 cm of small bowel ending in an ostomy and a colonic mucus fistula (retains ½ of her colon).  She is TPN dependent but struggling with adequate hydration due to high ostomy losses.  The next step in the management of this patient should be:

Encourage her to drink ample amounts of water

Encourage her to drink ample amounts of ORS

Refer her for surgery to restore intestinal continuity

Refer her for an intestinal transplant evaluation

Start teduglutide