1. Deirdre Hartigan 13th November 2011
Neonatal Parenteral Nutrition- ‘There’s a hole in my ‘tummy’ dear Liza, dear Liza!’
Deirdre Hartigan
13th November 2011

2. Overview of the workshop
Case study
12 questions
IFALD
NEC & SBS
Lipid sources
Parenteral
Nutrition
Complications of PN 2 2

3. Overview Case study IFALD 12 questions Lipid sources NEC & SBS
Parenteral
Nutrition
Complications of PN 3 3

4. Necrotising Enterocolitis
NEC is principally a disease of VLBW infants. The classical clinical triad consists of:
Abdominal distension
GI bleeding
Pneumatosis intestinalis (gas in the bowel wall)
Risk factors – prematurity, hypoxia, ischaemia, infection, exotoxin (from bacterial overgrowth and intestinal stasis), rapid advancement of feedings and exchange transfusions
Nearly all infants with NEC have received enteral feeding. However NEC does not develop in the vast majority of infants who have been enterally fed and there is no evidence that delaying enteral feedings and providing PN prevent the development of NEC.
Any part of the GIT can be involved but the ileum, colon and jejunum are the commonest sites. The spectrum of disease varies from a single, localised area ±perforation to involvement of the entire bowel.
The pathology starts with coagulation necrosis of the mucosa, progressing to ulceration, oedema and haemorrhage with bacterial infiltration. In extensive cases, there is transmural necrosis and perforation.

5. Definition
Necrotising enterolcolitis (NEC) is a medical condition primarily seen in premature infants where portions of the bowel undergo necrosis (tissue death)

6. Cause No definitive cause Infectious agent Weakened immune function
Intestinal flora
Alterations in mesenteric blood flood
Formula feeds

7. Cause No definitive cause Infectious agent Weakened immune function
Intestinal flora
Alterations in mesenteric blood flood
Formula feeds
NEC has no definitive known cause.3 An infectious agent has been suspected, as cluster outbreaks in neonatal intensive care units (NICUs) have been seen, but no common organism has been identified. Pseudomonas aeruginosa is suspected for causing necrotising enterocolitis in premature infants4 and neutropaenic cancer patients,5 often secondary to gut colonisation. A combination of intestinal flora, inherent weakness in the neonatal immune system, empirical antibiotic use for 5 days or more,6 alterations in mesenteric blood flow and milk feeding may be factors. The most common area of the bowel affected by NEC is near the ileocecal valve (the site of transition between the small and large bowel). NEC is almost never seen in infants before oral feedings are initiated. Formula feeding increases the risk of NEC by tenfold compared to infants who are fed breastmilk alone.7 Expressed breast milk protects the premature infant not only by its antiinfective effect and its immunoglobulin agents but also from its rapid digestion.
A study by the Neonatal Research Network, published in the journal Pediatrics in January 2009, conducted a study regarding the administration of empirical antibiotics in extremely low birth weight infants. The research demonstrated that empirical antibiotic therapy over 5 days for extremely low birth weight babies increased the chance of necrotizing enterecolitis by 4% for each additional day over 5 days.6

8. Once a child is born prematurely, thought must be given to decreasing the risk for developing NEC. Toward that aim, the methods of providing hyperalimentation and oral feeds are both important. A recent study, by researchers in Peoria, IL, published in Pediatrics in 2008, demonstrated that using a higher rate of lipid (fats and/or oils) infusion for very low birth weight infants in the first week of life resulted in zero infants developing NEC in the experimental group, compared with 14 % with NEC in the control group (They started the experimental group at 2 g/kg/d of 20% IVFE and increased within two days to 3 g/kg/d; Amino acids were started at 3 g/kg/d and increased to 3.5). (Drenckpohl D, McConnell C, Gaffney S, Niehaus M, Macwan KS. Randomized trial of very low birth weight infants receiving higher rates of infusion of lipid emulsions during the first week of life Pediatrics 2008;122; ).
Neonatologists at the University of Iowa NICU reported on the importance of providing small amounts of trophic oral feeds of human milk starting ASAP, while the infant is being primarily fed intravenously, in order to prime the immature gut to mature and become ready to receive greater oral intake (Ziegler and Carlson, J Matern Fetal Neonatal Med Mar;22(3):191-7.) Human milk from a milk bank or donor can be used if mother's milk is unavailable. The gut mucosal cells do not get enough nourishment from arterial blood supply to stay healthy, especially in very premature infants, where the blood supply is limited due to immature development of the capillaries, so nutrients from the lumen of the gut are needed.

9. Alimentary tract of infant showing intestinal necrosis, pneumatosis intestinalis, and perforation site (arrow). Autopsy.

10. Close up of intestine of infant showing necrosis and pneumatosis intestinalis. Autopsy.

11. Multi-system organ failure
Gut
Necrosis
Perforation
Peritonitis
Respiratory
Abdominal distension
Acidosis
RDS
Circulation
Septic shock
Hypotension
Blood
Coagulopathy
Platelets
Anaemia
Renal
Electrolyte imbalance
Fluid retention
Brain
Hypoxia
Perfusion injury
Typical recovery from NEC if medical, non-surgical treatment succeeds, includes 10–14 days or more without oral intake and then demonstrated ability to resume feedings and gain weight. Recovery from NEC alone may be compromised by co-morbid conditions that frequently accompany prematurity. Longterm complications of medical NEC include bowel obstruction and anemia.
Despite a significant mortality risk, long-term prognosis for infants undergoing NEC surgery is improving, with survival rates of 70-80%. "Surgical NEC" survivors are at-risk for complications including short bowel syndrome, and neurodevelopmental disability.

12. Short bowel syndrome
SBS

13. Short Bowel Syndrome
“malabsorption resulting from loss of part of the small intestine; inadequate absorptive area, and the physiological consequences”
“a reduction in the functioning intestinal mass below the amount necessary for adequate absorption to allow for growth”
Spectrum of malabsorption that occurs after resection of a major portion of small intestine
Need for prolonged parental nutrition secondary to intestinal failure
Short Bowel Syndrome: epidemiology and etiology Wales et al Toronto 2009

14. PIN THE TAIL ON THE DONKEY!
(…….kind of!)

15. Duodenum
Jejunum
Ileum
Ileocaecal valve
Descending colon

16. Severe malnutrition pre-PN era.
Successful long term PN in such a patient first described in
1968 by Wilmore and Dudrick
Severe malnutrition pre-PN era.

17. Overview Case study IFALD 12 questions Lipid sources NEC & SBS
Parenteral
Nutrition
Complications of PN 17 17

18. SBS Outcomes Numerous series of SBS patients have been reported
survivals ranging from 50% to 80%.
Greater than 38cm good survival 1,2
and again 2004
1. Wilmore DW. Factors correlating with a successful outcome following extensive intestinal resection in newborn infants.
Pediatr 1972;80:88-9
2. LONG-TERM PARENTERAL NUTRITIONAL SUPPORT AND INTESTINAL ADAPTATION IN CHILDREN WITH SHORT BOWEL SYNDROME:
A 25-YEAR EXPERIENCE
RUBE´N E. QUIRO´ S-TEJEIRA, MD,MARVIN E. AMENT, MD, LAURIE REYEN, RN, FAYEHERZOG, RN,MICHELLEMERJANIAN, MD,
NANCYOLIVARES-SERRANO, MD, AND JORGE H. VARGAS, MD The Journal of Pediatrics August 2004
Short gut – 38cm
Very short gut - <38cm
Ultra Short gut <15cm 18

19. Outcomes ¾ survived in 2004 study with < 15cm bowel
50% survival in 1970s 15-38cm
ICV improved outcome 19

20. Outcomes Survival (neonatal) < 40 cm (n = 35) 67%
(Goulet et al, 1991)
¾ survived in 2004 study with bowel <15cm 20

21. Outcomes Prognosis newborn, full enteral feeding established:
<40 cm mean 27 months (3 - 84)
cm mean 14 months (1 - 70)
(Goulet et al, 1991)

22. Outcomes
4 year old girl, 12cm jejunum following midgut volvulus; survived without PN! (Surana et al. JPGN 1994;19: )
survival 8/9 patients without ileocaecal valve and < 40 cm small bowel
(Chaet et al. JPGN 1994;19: )

23. Surgery To get off PN: Bianchi (bowel lengthening)
STEP (serial transverse enteroplasty)
Indications poorly defined.
Need dilated bowel

24. Bianchi bowel lengthening procedure

25. STEP procedure

26. Selective Decontamination of Digestive system (SDDS)
Cyclical antibiotics
Metronidazole + Trimethoprim + fluconazole (LTH)
Gentamicin + Metronidazole + Co-trimoxazole
Polymyxin E/Colistin + Tobramicin + Amphoteracin
Rifaximin > 2 years of age (LTH)
2 weeks on, 2 weeks off (LTH)

27. Overview Case Study IFALD 12 questions Lipid sources NEC & SBS
Parenteral
Nutrition
Complications of PN 27 27

28. Intestinal Failure Associated Liver Disease (IFALD)
Parenteral Nutrition Associated Cholestasis (PNAC)
Parenteral Nutrition Associated Liver Disease (PNALD)
Intestinal failure occurs when the gastrointestinal tract is unable to ingest, digest and absorb sufficient macronutrients and/or water and electrolytes to maintain health and growth
clinical presentation most commonly as jaundice (type 2)
conjugated bilirubin >50 μmol/L is a manifestation of significant liver disease
urgent review by NST with access to specialist hepatology advice
diagnosis of IFALD should prompt multi-professional review of enteral and parenteral nutrition

29. IFALD – Risk factors Prematurity IUGR Lack of enteral intake Lipid
Early CVC infection
Co-morbidity
Early = < 4 weeks.

30. IFALD – Risk factors Short bowel Dysmotility Bacterial overgrowth
Frequent CVC infections (>3/year)
Poor aseptic technique
Long hospital in-patient stays

31. Overview Case study IFALD 12 questions Lipid NEC & SBS sources
Parenteral
Nutrition
Complications of PN 31 31

32. Intralipid 20% Developed in the 1960s Purified soybean oil
Mainly Omega 6 fatty acids
60% polyunsaturated fatty acids (PUFA)
23% monounsaturated fatty acids (MUFA)
Reliable source of essential fatty acids
Long chain PUFAs play a crucial role in pathogenesis of PNALD.
phytosterols in soy emulsions
ω-6 pro-inflammatory; oxidative damage

33. Clinoleic 20% Olive oil based lipid soybean + olive oil
long chain fatty acids
20% PUFA
65% MUFA
 intake PUFA
Clinoleic – more physiological in his fatty acid profile.
Clinoleic has a fatty acid profile that closely matches the recommended normal diet.

34. Fish Oil
‘Reversal of Parenteral Nutrition-Associated Liver Disease in Two
Infants With Short Bowel Syndrome Using Parenteral Fish Oil:
Implications for Future Management’
Gura et al. Paediatrics 2006; 118;
‘The rationale for the use of parenteral omega-3 lipids in children
with Short bowel syndrome and liver disease’
Diamond et al.Pediatr Surg Int (2008) 24:
‘Rescue treatment of infants with intestinal failure and parenteral
nutrition-associated cholestasis (PNAC) using a parenteral fish-
oil-based lipid’
Cheung at al. Clinicl Nutrition 28 (2009)

36. Omegaven 10% Fish oil based lipid Rich in Omega 3 Improves bile flow
Decreased steatosis
Immunomodulatory effects
High percentage of very long chain omega 3 fatty acids.

37. SMOF Lipid® Soybean oil Medium-chain triglycerides (MCT) Olive oil
Fish oil
(with additional vitamin E to counteract lipid peroxidation and oxidative stress) 37

38. Overview 38 Case study IFALD 12 questions NEC & SBS Lipid sources
Parenteral
Nutrition
Complications of PN 38 38

39. Complications of PN - CVC
Occlusion
Infection
Catheter misplacement
Haemorrhage
Thrombosis
Air embolism
Breakage/leakage
Prevention of CRBSI is extremely important in order to save precious lines and venous access

40. Line Locks Taurolock® - 2% Taurolidine (antimicrobial)
- 4% citrate (prevents thrombus formation)
All LTH line locks = 2mL
Instil 2ml into each lumen of line and leave for as long as possible. Aspirate before connecting PN or using the line eg to give next dose of antibiotics
Taurolock – a catheter lock solution for tunelled and non-tunnelled CVCs and ports. 2% Taurolidine as the antimicrobial component and 4% citrate to prevent clots.
antiseptic with a broad range of activity against gram positive and gram negative bacteria and fungi. It is a derivative of taurinamide, a naturally occurring aminosulphonic acid and formaldehyde. In vitro experiments have demonstrated efficacy in preventing and eradicating the catheter bio-film caused by a variety of Gpos and Gneg bacteria and Candida albicans

41. Taurolock® Broad spectrum bactericidal activity Not an antibiotic
gram negative & positive organisms
fungi
Not an antibiotic
No antimicrobial resistance
Irreversible binding of its methylol groups to the cell walls of the organism
Prevents biofilm formation

42. Taurolock ® Minimal side effects
Reversible thrombocytopenia & neutropenia
Severe localised pain
Unusual taste in mouth

43. LTH Data
Patient
Total catheter days
CRBSI episodes
pre Taurolock®
post Taurolock®
CRBSI/1000
catheter days 1
1064 2
4394 3
0.87
3290 12
4.4 4
2018
5.26 5
914
8.7 6
1340 9
10.9

44. And Finally
Thank you! 44 44