04 Duggan IF for Neonatology Conference 2014 mp.ppt fileNEC, Hirschprung’s disease, abdominal wall...

Management of Short Bowel Syndrome in the Neonate

Christopher Duggan, MD, MPHMedical Director,

Center for Advanced Intestinal Rehabilitation (CAIR)Boston Children’s HospitalHarvard Medical School

Boston, MA

DISCLOSURE

I have no pertinent financial relationship with a commercial entity producing health‐care related products and/or services.

FDA – Nothing to disclose

Case Presentation: SF

• In another hospital..

– 30 week AGA infant developed bilious emesis and abdominal distension

– KUB showed diffuse pneumatosis intestinalis and free air

– Exploratory laparotomy showed ischemic bowel of most of jejunum and ileum; massive resection leaving 5 cm of jejunum and unknown health of ileum; ‘NEC totalis’

– Abdominal silo placed

– View of bowel via silo showed ischemia

– DNR, support withdrawn

Learning Objectives

• Definitions, etiology and natural history of IF

• To review indications for intravenous fat emulsions

• To review strategies for parenteral• To review strategies for parenteral micronutrient supplementation in the setting of manufacturing shortages

• Future directions

Learning Objectives





Definitions of Intestinal Failure

• “Reduction of functional intestinal mass necessary for adequate digestion and absorption for nutrient, fluid and growth requirements”

• 3 major classifications– Short bowel syndromey– Motility disorders– Intestinal epithelial defects

• Short Bowel Syndrome– “Intestinal resection for acquired or congenital intestinal disease leading to dependence on parenteral nutrition for > 90 days”

Another “functional” definition.. At the end of colonoscopy..

Prognostic Factors in Children with SBS

• Residual small bowel length

– Benson 1967; Wilmore, 1972; Galea 1992; Kurkchubasche 1993; Chaet 1994

• Ileocecal valve preservation

– Goulet 1991

• Jejunal vs. ileal resection

• Absence of mucosal disease

• Preservation of colon

• Younger age– Caniano 1989

1

2

3

4

Pro

bab

0.6

0.8

1.0

Logistic Analysis Curve: Theoretical Relationship between Odds of Weaning from PN and Residual SB length

Residual Small Bowel Length (cm)

0 10 20 30 40 50 60 70 80 90 100 110

Nu

mb

er o

f P

atie

nts

3

2

1

0

ility of W

eanin

g

0.0

0.2

0.4

WeanedNot Weaned

Theoretical Probability

Andorsky, et al., J Pediatr 2001; 139:27

• January 2003 – December 2005

• All children undergoing laparotomy at TSC

• 24 weeks GA – age 5 years

• Excluded with “long segment or circumferential”

Struijs et al., J Pediatr Surg 2009;44:933

• Excluded with long segment or circumferential NEC, Hirschprung’s disease, abdominal wall defects or Z scores > 2 or < ‐2

• “Upon entering the abdominal cavity, the small and large intestines were measured in situ along the anti‐

mesenteric border using a 3‐0 silk suture.”


Struijs et al., J Pediatr Surg 2009;44:933 Struijs et al., J Pediatr Surg 2009;44:933


• 473 infants enrolled

• 464 confirmed NEC diagnosis

• 180 underwent surgery

• 284 did not

• 70 had early death or follow‐up < 90d

• IF occurred in 42% of surgical infants vs. 2% of those without surgery

• OR 31.1 (12.9 – 75.1)

J Pediatr 2012; 161: 723-728 J Pediatr 2012; 161: 723-728

J Pediatr 2012; 161: 723-728

Percent of Patients on PN with Septic Events by Study Interval

n P

N w

ith

posi

tive

cul

ture

50

60

70

80

90

Bacterial215 11

55 2615

9

• 8.9 new catheter-related blood stream infections / 1,000 catheter days

Perc

ent o

f pa

tient

s on

Interval following entry into the study (months)

0

10

20

30

40

50

Base 1m 3m 6m 9m 12m 24m 36m 48m 60m 72m

Fungal

Polymicrobial

Poly + Fungal265

235

215189 140

7

Exposure to medications at any time during study period

Percent of Patients

Variable enteral feeding practice

Formula Number of times

Choice for initial enteral feeding

Pregestimil® 111

Neocate Infant Formula® 83

Elecare® 13Elecare® 13

Vivonex Pediatric® 10

Alimentum® 7

EnfaCare® 3

Neocate Junior® 3

13 other distinct formulas 20

All others 4

Ever on breast milk 52 (19%)

Reported Abdominal Surgical Procedures in 272 patients from Birth

Surgical Procedure Number

Small bowel resection 336

Exploratory laparotomy 202

Ostomy creation, revision, closure 209

Gastrostomy creation/revision/closure 218Gastrostomy creation/revision/closure 218

Lengthening procedure 28

Bianchi = 13 (1 before study entry)

STEP = 15 (5 before study entry)

Tapering procedure 14

Fundoplication 19

Other procedures 200

TOTAL PROCEDURES 1226

Citrulline Metabolism

Clinical Nutrition. 2008; 27 (3): 328-339

Gastro. 2003; 124: 1210-1219

Citrulline in SBS

J Peds. 2005; 146 (4): 542-7.

Relationship to PN dependence

Fitzgibbons S et al. J Pediatr Surg.

20

25

30

line

( m

ol/L

)

Minimum Citrulline Significantly Lower in Patients with CRBSI

CRBSI (n = 26) No CRBSI (n = 25)0

5

10

15

20

Min

imu

m S

eru

m C

itru

ll

___

___

P = .004, Student t-test

6.7

11.3

Hull et al., JPEN 2011

CR

BS

I (%

)

60

70

80

90

100

5 mol/L10 mol/L15 mol/L20 mol/L

Minimum Citrulline

Serum Citrulline, Catheter Duration, and CRBSI

Duration of Catheter (months)

3 6 9 12 15 18 21 24

Pro

bab

ility

of

C

0

10

20

30

40

50

Learning Objectives





• 78 patients with – PN dependence for > 3 months

– SBS defined as < 75 cm residual small bowel

J Pediatr 2004; 145:157-63

• 57/78 (73%) alive median age 9 years– Median follow-up: 9 years

– Range of follow-up: 2.1 – 23 years

Correlation of survival with cholestasis

J Pediatr 2004; 145:157-63

PN-associated liver disease

Nutrient deficiency PN toxicity

TaurineCholineEFAVitamin EZinc

EnergyProteinIndividual amino acidsFats

Among the 168 infants with sufficient data to assess forthe presence of cholestasis at baseline, 125 children hadcholestasis, and their cumulative percentage of survivalwas significantly lower than in the 43 without cholestasis(79% vs 95% at 1 year, and 73% vs 88% at 3 years;P = .03).

• Cohort study of 464 infants with NEC

Duro et al., JPGN 2011

• Enrolled across 6 centers

• 2004 – 2007

Experience with Omega 3 fatty acids

Gura K et al., Pediatrics 2006; 118:197-201

• 18 infants with SBS who developed cholestasis were

– Taken off IL

– Placed on Omegaven (1 g/kg/d)

• Historical cohort of 21 infants followed at same institution

Pediatrics 2008; 121:e678

Direct bilirubin trends

Pediatrics 2008; 121:e678

Sci Transl Med. 2013 Oct 9;5(206):206ra137.

J Pediatrics 2011

Controversies

• Is it safe to provide so many calories using parenteral dextrose?

– Dalton et al., NASPGHAN 2013

• Is it effective to limit fat to 1 g/kg/d re• Is it effective to limit fat to 1 g/kg/d re: cholestasis prevention?

– Nehra et al., JPEN 2013

– Levit et al., PAS 2013

• 61 infants with surgical GI disease who• 61 infants with surgical GI disease who received PN for at least 3 weeks at BCH

• 29 received 1 g/kg/d of IL

• 32 received 2‐3 g/kg/d

“Our” Current Approach

• Limit IL dose to 1 g/kg/day among all patients likely to be on PN for > 3 weeks

– NAC

Including NICU– Including NICU

– Make up calories with dextrose

• If a patient meets criteria for Omegaven protocol, switch them to 1 g/kg/day of this experimental therapy

Learning Objectives





“Total” parenteral nutritionPrevalence of micronutrient

deficiencies during PN weaning

Yang et al., J Pediatr 2011

Prevalence of micronutrient deficiencies during full EN

Yang et al., J Pediatr 2011

Parenteral component shortages

• Phosphate

• Multivitamins

• Trace elements

• Ethanol

http://www.fda.gov/Drugs/DrugSafety/DrugShortages/ucm142398.htm

• 3 premature infants in NICU with cholestasis and PN dependency developed skin lesions

• Blood, urine, CSF and wound cultures were negative

Parenteral Component Shortages

• Raw material shortages

• Discontinuations

• Fewer manufacturing firms

• Limited capacity of remaining companies to increase supplies

SBAR: 4/24/2013 Medication BackordersS Sodium Phosphate and Potassium Phosphate are on national backorder at this time.

B These products are used in parenteral nutrition, hypophosphatemia, and in diabetic ketoacidosis IV fluids. These electrolytes have been on backorder with small allocations for a period of time and supply is now almost depleted.

A 1. Sodium Phosphate 3 mmol/mL injection – 3 vials remaining2. Potassium Phosphate 3 mmol/mL injection – 5 vials remaining

R Effective immediately 4/24/2013R Effective immediately – 4/24/2013· Sodium Phosphate injection – Supply is depleted except for a very small number of vials (3). These vials will be sequestered for ICU emergent use and/or in the DKA patient population. Pharmacy is expecting a shipment by the end of this week.· Potassium Phosphate injection– Supply is almost depleted except for a very small number of vials (5). This product will be sequestered for ICU emergent use and/or in the DKA patient population.· DKA floorstock fluids as they currently exist will no longer be manufactured by Pharmacy due to this backorder. · Phosphate will NOT be included in parenteral nutrition mixtures at this time.

Courtesy Home PN Program, Boston Children’s Hospital

Recommendations for Trace Element ShortagesFor patients receiving 7 nights of parenteral nutrition (PN) and/or <50% enteral feedsBiochemical monitoring: complete blood count (CBC) with differential, copper, ceruloplasmin c-reactive protein (CRP), vitamin A**Vitamin A to be checked if not monitored in the past 6 months. Rationale: evaluate for risk of hypervitaminosis A

Patients 2 years and older:Start Flintstones® Complete multivitamin for supplementation

Patients under 2 years of age:Provider discussion

For patients receiving less than 7 nights of PN and >50% enteral feeds:Biochemical monitoring: CBC with differential, copper, ceruloplasmin, CRP at time patient is impacted. If impacted by zinc or selenium shortage, monitor these levels No additional supplementation needed. Encourage copper (zinc if applicable) rich foods (see appendix)Repeat CBC with differential, copper, ceruloplasmin (zinc and selenium as applies) in 2 months’ time

Courtesy Home PN Program Boston Children’s Hospital

Conclusions

• Shortages of components of PN have significant implications for our patients.

– Can FDA be convinced to allow other European products into the US market?products into the US market?

• Biochemical monitoring is critical to document nutrient deficiency states.

• Advocacy efforts must continue.

Learning Objectives






• In another hospital..

– 30 week AGA infant developed bilious emesis and abdominal distension

– KUB showed diffuse pneumatosis intestinalis and free air

– Exploratory laparotomy showed ischemic bowel of most of jejunum and ileum; massive resection leaving 5 cm of jejunum and unknown health of ileum; ‘NEC totalis’

– Abdominal silo placed

– View of bowel via silo showed ischemia

– DNR, support withdrawn


• September 2010

– Removal of silo and placement of proximal loop jejunostomy

– Only 6 cm of jejunum noted distal to TrietzOnly 6 cm of jejunum noted distal to Trietz

– Parenteral nutrition

• Omegaven

– NICU supportive care

Growth

Omegaven/Lipid restriction


• December 2010

– Takedown of jejunostomy with primary SB anastomosis

– Distal SB in continuity but enteral fistula held theDistal SB in continuity but enteral fistula held the intestine in circular whorl – this was opened

– SB stricturoplasty

– Ileocectomy and ileocolonic anastomosis

– Liver biopsy and G‐tube

DIVERTING LOOP JEJUNOSTOMY

Courtesy Dr. Terry Buchmiller

FISTULA AT FORMER ILEAL RESECTION MARGIN 49 cm RSB

Unused distal bowelUnused distal bowel

Courtesy Dr. Terry Buchmiller

Fistula


• February 2011

– Good weight gain

– 40% enterally fed

Discharged home– Discharged home

Number of Intestine transplants per year

150

200

250

0

50

100

150

1998

1999

2000

2001

2002

2003

2004

2005

2006

2007

2008

2009

2010

2011

2012

Intestine, no liver

Intestine, with liver

Total

OPTN/SRTR 2012 Annual Data Report: Intestine (unpublished data)

Learning Objectives





Center for Advanced Intestinal Rehabilitation at Children’s Hospital Boston

04 Duggan IF for Neonatology Conference 2014 mp.ppt fileNEC, Hirschprung’s disease, abdominal wall...

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