Transcript Introducing a new practice on the NICU: Probiotics

Introducing a new practice on
the NICU: Probiotics
A James1
H Tranter2
A Davies1
S Cherian2
Royal Gwent Hospital1 &
University Hospital of Wales2
Background
• Necrotizing enterocolitis (NEC) is a major cause of
morbidity and mortality in preterm infants
• Affects 6-7% of VLBW infants
• Economic burden of NEC is significant
• Probiotics are live micro-organisms when
administered in adequate amounts confer a health
benefit on the host
– Improved gut barrier
– Enhanced mucosal IgA response
– Increased production of antiinflammatory cytokines
Reducing the risk of NEC and
death in preterm infants
Shlomai NO et al Neonatology 2014
Probiotics for infants < 1500 g:
Preventing severe NEC (stage II-III)
NNT 25
AlFaleh et al Cochrane Reviews 2014
Probiotics for infants < 1500 g:
Reducing mortality
NNT 33
AlFaleh et al Cochrane Reviews 2014
Species of probiotic:
Prevention of severe NEC
Probiotic species:
Reducing mortality
Infloran
• Contains Lactobacillus acidophilus and
Bifidobacterium bifidus
• The most widely studied product
• Babies receive a daily dose of 109 of each live
bacterial species
• Not licensed as a medicine, categorised as a
supplement in UK
• Low cost intervention- approx £1 per
treatment per day per baby
Introducing change
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Literature review, discussions within units
Microbiology: Drug samples obtained, cultured
Public Health, IPCNG: discussions, review
Pharmacy, Medicines group: discussions, review
Presented to Directorate Clinical Governance
Business case, presented to Trust Finance
Guidelines prepared, PIL prepared
Staff education
Cost of Infloran
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Estimated number of infants: 70
Estimated median duration: 7 weeks
Cost per capsule: £0.90
Cost per patient: £44.10
Cost per year: £3087
Cost of treating NEC
• Increased direct hospital cost:
• ‘Medical’ NEC: $ 14,000
• ‘Surgical NEC’: $23,000
• Estimated 5cases/year/unit: $80,000/£50,000
• NB: 2009 CPI, USA
Johnson T et al J Pediatrics 2013
Collaboration
• PINC UK: Probiotics In Newborns Collaboration
• Newcastle, Bradford, Norfolk & Norwich
• Eligible infants: <32 weeks gestation
<1500g birth weight
< 7 days old if outborn, no NEC
PINC UK
• Study period: 01/05/2013- 30/04/2014
• Control period: 01/05/2012-30/04/2013
Infloran prescription
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Infloran: 109 bacilli LBA and BBB in 250mg
Dose is 125mg twice daily
Quality control data available
MHRA no objection to use in a hospital setting
Prescribed as drug for quality control and
safety reasons
• Pharmacy procures, maintains cold chain
Preparation & administration
• Preparation in designated area in milk kitchen
• Capsule contents dissolved in 1ml water, 0.5ml
administered as a bolus
• Can be started when feeds of 0.5ml tolerated
• Not to be administered if on continuous feeds
• Consider stopping if unwell, feeds stopped
• Safe to administer if on steroids
Results: Eligible infants
Study group
Control group
Number
164
170
Gestation median (full range) weeks
30 (23-37)
29 (23-39)
Birth weight median (full range) grams
1270 (420-2370)
1223 (520-2170)
Study group
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Probiotics received
Age at start (Median)
Age at start (Min)
Age at start (Max)
130
5 days
1 day
58 days
Study group
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Duration of administration of probiotics:
Median
17 days
Min
1 day
Max
65 days
Outcomes
Study group (n=164)
Control group (n=170)
Probiotics given
130
0
NEC ≥ stage2*
14
13
Deaths (all causes)*
17
15
Positive blood cultures*
26
34
*Fishers exact test NS
Reason for
non-administration
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Died before starting feeds
Transferred out before feeds started
>34 weeks when feeds started
>34 weeks on 01/05/2013
Missed
8
4
9
3
10
Cause of death
Study
• Extensive NEC
• Sepsis
• Complications of prematurity
• Congenital anomalies
• Twin to twin transfusion
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2
7
1
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Control
• Extensive NEC
• Sepsis
• Complications of prematurity
4
1
10
Newport, Cardiff:
Study group
Newport (n=93)
Cardiff (n=71)
Probiotics given
80
50
NEC ≥ stage2
11
3
Deaths (all causes)
7
10
Reducing the risk of NEC and
death in preterm infants
✓
✓
✓
Shlomai NO et al Neonatology 2014
Confounding factors
2013 VON Annual reports for Newport and Cardiff
Newport (%)
Cardiff (%)
VON
Network(%)
Antenatal steroids
86.3
86.6
82.9
Any human milk on discharge
43.3
47.5
57.3
Only human milk on discharge
20
12.5
11.7
Ibuprofen for PDA
22
1.6
8.1
Major congenital anomalies
1.7
10.4
4.4
Small for gestational age
30.5
35.8
24.7
NEC
13.9
1.6
4.5
? Differences in population, microbiome
NEC in Japan
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Incidence 0.2%-1.6%: ? reason
Exclusive breast milk <28 w infants
Full feeds in 7 days
Avoid UVC insertion
Early use of PIC lines
Probiotics
Minimal handling
Use antibiotics only if certain of infections
Isayama T et al Pediatrics 2012
Lee SK at SIGNEC 2014
EPIQ Canada
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Evidence Based Practice for Improving Quality
All tertiary NICUs in Canada
Included all infants <29w gestation
For reducing NEC: practice changes implemented
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Standardised feeding guidelines
Early feeding
Use of donor milk
Colostrum & enhanced breast milk feeds
Early TPN
Hold enteral feeds during blood transfusions
Lee SK CMAJ 2014
EPIQ Canada
• NEC reduced significantly
• Pre: Post intervention: 10% vs 8%, OR 0.73 (.52-.98)
• Effective practices were:
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Standardised feeding guidelines
Early feeding
Use of donor milk
Colostrum & enhanced breast milk feeds
Early TPN
Hold enteral feeds during blood transfusions
Lee SK CMAJ 2014
Conclusions
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Introduced routine probiotic use on 2 NICUs
Safe: No sepsis with probiotic organism
No difference in NEC, sepsis or death
Small numbers
Need to improve breast feeding both centers
? Consider holding enteral feeds during
transfusions at Cardiff (TANEC audit)