standard aio paediatric pn clinical results zorgaanbod... · 2019-10-18 · ideal weight class <...
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Standard AIO Paediatric PN –Clinical results
5e Symposium klinische farmacie UZ Gent
15-10-2019
De Cloet Joeri / Pharmacy Department
Critical importance in neonates, infants and adolescents
Fast growth
Very limited body reserves
• High nutritional requirements/kg body weight
Immature GI system, metabolic and renal functions
Tissue and organ development
• e.g. brain
Unbalanced/insufficient nutrient supply leads to a higher risk of developing a certain
condition in adulthood ("programming of human health")
• eg diabetes, allergy, IBD, obesity, ...
Well balanced Parenteral Nutrition formula
Standard versus individualized paediatric PN
Advantages Standard paediatric PN
Less prescription errors (inadequate or erroneous calculation of nutritional needs)
Less preparation errors (physico-chemical incompatibilities)
Beter Quality control (batch wise produced)
Less time consuming
Immediately available
Cost benefit
Less risk of infection (less manipulation)
Advantages Individualized/ tailored paediatric PN
More tailored on a daily basis to suit specific needs
Very critical patients with metabolic disturbances (eg HyperK)
Paediatric TPN-admixtures before june 2008
No commercial available standard AIO admixtures
No sufficiently stable AIO admixtures – Binary PN formulations + lipids in Y-site
Trial and error - tailored formula for HOME-TPN patients
CHALLENGE !!!
Design well balanced standard AIO (binary) admixtures
based on ESPGHAN/ESPEN guidelines 2005
High elektrolytes (Ca2+ and PO4-3) with lipids
Dosage on ideal body weight (= target weight)
Well-known long-term stability
Difficulties in paediatric PN practice
.KOLETZKO, B., ET AL., GUIDELINES ON PAEDIATRIC PARENTERAL NUTRITION. ESPGHAN /ESPEN. JOURNAL OF PEDIATRIC GASTROENTEROLOGY
AND NUTRITION, 2005. 41: P. S1-S87.
Ideal weight class
< 3 Kg 3 kg – 10 kg 11 kg – 20 kg 21 kg – 30 kg > 31 kg (- 18 year)
Neonatal
TPN:
A-B-C
TPN PED 1 TPN PED 2 TPN PED 3 TPN PED 4
Type TPN
HOSPITALISATION BINAIR HOME
Gluc, AA, elektrolytes, Vit
and trace elements
+
Lipids: 2 g/kg/dag
=
All-in-one TPN via 1 central
line
Gluc, AA, elektrolytes, Vit
and trace elements
No Lipids
Gluc, AA, elekrolytes, Vit and
trace elements
+
Lipids: 1 g/kg/dag (“HOME TPN”
administration < 24 u/dag )
Fat content is compensated in
calories by means of ½ gluc
Standard Paediatric TPN admixtures University Hospital Ghent
2-compartment EVAM bags
Compartment A: Lipids (Smoflipid 20%)
Compartment B: Gluc + AA + E (Na+, K+, Ca2+, Mg2+, PO43-)
Time intervals: 0h - 20D (2-8°C)+ 24h RT – 50D (2-8°C)+ 24h RT - 80D (2-8°C)+ 24h RT
A: physically: - Visual inspection (phase separation)
A+B+VIT+TE - Sudan Red test (free oil droplets)
- pH
- Lipid droplet size distribution (MDD < 0,5 µm)
chemical: - NEFA (hydrolysis)
- Peroxide (oxidation)
B: physically: - Visual inspection (Ph. Eur. precipitation and disclororation)
- pH
chemical: - Gluc
- L-cysteine, L-tyrosine, L-tryptophan
-- J. De Cloet et al. Nutrition 2018 49:41-47
6 /
Physico-chemical Stability study
Results
--
7 /
Physico-chemical Stability study
Physical stability of lipid compartment A and AIO admixture A+B+VIT+TE (protected from light)
Compartment A Admixture A+B+VIT+TE
Time PED 1 PED 1+E PED 1 PED 1+E
Days (2-8°C) + hours (RT) MDD (nm) MDD (nm) MDD (nm) MDD (nm)
0 312 315 317 317
7 D + 48 h ND ND 312 312
20 D + 24 h 320 315 318 317
20 D + 24 h + 7 D ND ND 316 316
20 D + 24 h + 7 D + 48 h ND ND 318 317
50 D + 24 h 330 326 315 315
50 D + 24 h + 7 D ND ND 318 315
50 D + 24 h + 7 D + 48 h ND ND 315 313
80 D + 24 h 319 320 316 314
80 D + 24 h + 7 D ND ND 313 324
80 D + 24 h + 7 D + 48 h ND ND 319 324
MDD: mean droplet size diameter, D: days, h: hours, RT: room temperature, ND: not determined
0,00
0,50
1,00
1,50
2,00
2,50
3,00
0 20 D + 24 h 50 D + 24 h 80 D + 24 h
me
q/L
Time
Peroxide and NEFA concentration
Peroxide number PED 1Peroxide number PED 1+ENEFA PED 1NEFA PED 1+E
90%
95%
100%
105%
110%
0 20 D + 24 h 50 D + 24 h 80 D + 24 h
% o
f gl
uco
se
Time
Glucose analyses
Glucose PED 1
Glucose PED 1+E
85%
90%
95%
100%
105%
110%
0 20 D + 24 h 50 D + 24 h 80 D + 24 h
% o
f am
ino
aci
ds
Time
L-Tryptophan and L-Tyrosine analyses
L-Tryptophan PED 1
L-Tryptophan PED 1+E
L-Tyrosine PED 1
L-Tyrosine PED 1+E
0,0%
10,0%
20,0%
30,0%
40,0%
50,0%
0 20 D + 24 h 50 D + 24 h 80 D + 24 h
% o
f L-
cyst
ein
e
Time
L-Cysteine analyses
L-Cysteine PED 1
L-Cysteine PED 1+E
J. De Cloet et al. Nutrition 2018 49:41-47
Objectives
• Effectiveness
• Weight evolution
• Safety
• Metabolic complications
• Catheter related complications
Study design
Retrospective - observational
Inclusion period: june 2008 – march 2011
Paediatric setting non-ICU: 3 – 40 kg
≥ 5 days TPN
Study evaluation of paediatric AIO admixturesfor hospitalized patients
MethodologyDatacollection via registration form EPD/nursing records
• Age, gender, indication, medical history, weight / length evolution
• Laboratory parameters
• Elektrolytes Na, K, Ca, Mg en P
• AST/ALT/APase/GGT
• TG/bilirubine (total en direct)
• CRP
• Fluid balance
• Start/stop-reason
• Complications (metabolic, catheter related, infection,...)
• Concomitant medication
Study evaluation of paediatric AIO admixtures
for hospitalized patients
Results
85 paediatric patients ~ 123 episodes of PN
Indication:
• 22% PDD (SBS, intractable diarrhea of infancy, major abdominal surgery,… )
• 78% PNDD (Hemato-onco, immunodeficiency,…)
Median age of onset: 5,6 years
Mean PN duration: 16,3 days
Study evaluation of paediatric AIO admixtures
for hospitalized patients
Effectiveness
Weight gain
Observed mean weight gain and P-value for the hospitalized (HOSP) paediatric patients
Population # Episodes Mean weigth gain (g) P-value
HOSP (total cohort) 94 606 < 0,001
TPN PED 1 (3-10 kg) 17 526 0,006
TPN PED 2 (11-20 kg) 43 343 0,007
TPN PED 3 (21-30 kg) 21 743 0,003
TPN PED 4 (31-40 kg) 13 1396 0,028
Study evaluation of paediatric AIO admixtures
for hospitalized patients
Safety – metabolic complicationsParameter Result Main cause
Elektrolytes(Na, K, Ca, Mg, P)
Hypo-K (1,7 %)Concomitant med (81,5 %); 0% TPN-related
Hypo-Mg (6,8 %)Concomitant med (81,8 %); 0% TPN-related
Glycemia (hypo-, hyper-) 7,3% ~ 99% Hyperglycemia Concomitant med (86%); 6% TPN-related
Liver damage(AST, ALT)
8,5% increased ASTConcomitant med (5,7%); 0% TPN-related
9,4% increased ALT Concomitant med (7,5%); 0% TPN-related
Cholestasis (Bili total, Bili direct, GGT, APase)
23,5% increased Bilirubine total Concomitant med (17,6%); 0% TPN-related
29,4% increased Bilirubine directConcomitant med (23,5%); 0% TPN-related
40,8% increased GGTConcomitant med (19,7%); 4% TPN-related
9,9% increased APaseConcomitant med (7,5%); 1,2% TPN-related
Study evaluation of paediatric AIO admixtures
for hospitalized patients
Safety - Catheter related
• Infectious
• HOSP-population: total 1823 TPN-days:
• 2 new infections
• Coagulase-Negative Staphylococci
• Occlusion
• None
Study evaluation of paediatric AIO admixtures
for hospitalized patients
Objective:
1. Examine current tailored PN policy/therapy PICU
2. Comparison with ESPEN / ESPGHAN guidelines
3. Use of Standard AIO admixtures possible PICU?
Method:
Prospective – observational (2009)
Critically ill pediatric patients (1 month - 15 years)
• excl. PN bij transfer ward
Datacollection similar “HOSP general ward study”
Study evaluation of paediatric AIO admixtures
for PICU
Tailored AIO PN policy• Inadequate macronutrient supply D1 – D3 • After D3 cumulative energy deficit (inadequate gluc supply)• Excessive fluid administration in 21% (intermittent medication)
Standardisation• From D1 the nutritional needs of the patient are met
↘ risk of nutritional deficiencies• Standard admixtures comply equal or even better with the ESPEN/ESPGHAN
guidelines• Standardization in PICU achievable for more than 2/3 (76%) of patients in analogy
with previously published data ~ 68% of all prescriptions (Krohn et al. Clinical Nutrition 2005)
Main findings
Study evaluation of paediatric AIO admixtures
for PICU
Objectives• Effectiveness and safety PN therapy infants and children on HPN
• Focus on standard paediatric PN admixtures
Study designRetrospective cohort study
< 18 years
Discharged on HPN between 1 jan 2000 – 30 apr 2016
• Cohort 1 : Individual compounded admixture (before june 2008)
• Cohort 2: Standard AIO admixtures (june 2008 – present)
Evaluation and follow-up paediatric patientson HPN 2000 – 2016
Data collection Medical and pharmacy records
Patient characteristics:
• Age , gender, diagnosis and indication for HPN
• Residual gut length, conservation of ileocecal valve and colon
• The age at onset HPN, duration of HPN, frequency and reason HPN discontinuation
• Growth curve: weight, length, BMI
Complications during HPN:
• Number, length and reason hospitalisation
• Number and type of complications (infectious – metabolic – catheter related)
Laboratory data
Concomitantly used medication
(Liver biopsy if available)
Evaluation and follow-up paediatric patientson HPN 2000 – 2016
• Demography
• Total 34 patients on HPN between 2000 - 2016
• 19 boys - 15 girls
• Median age at HPN onset = 0,6 year [0,2 – 17,6]
• Median duration of HPN = 11,0 months [0,3 – 169,6]
• Indications/underlying disease
• PDD: SBS (47%), Congenital enteropathies (15%)
• PNDD: Oncological (18%), IDS (12%)
• Outcome
• 19 children succesfully weaned off• 8 patients continuing HPN• 6 patients died • 2 patients ITx
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Number of newpatients startingon HPNNumber ofpatientscontinuing HPN
Evaluation and follow-up paediatric patients
on HPN 2000 – 2016
Results 2008 - 2016Cohort 2 standard AIO admixtures
Effectiveness ~ growth1) Weight & Length
Weight increase
Population Number Mean (kg) SD Median Range P-value
TPN PED 1 13 4,04 1,88 3,82 (1,66 - 7,19) 0,001
TPN PED 2 7 5,69 2,92 4,89 (3,00 - 11,54) 0,018
TPN PED 3 2 9,16 3,32 9,16 (6,81 - 11,50) 0,180
TPN PED 4 4 7,15 4,70 6,20 (2,80 - 13,40) 0,068
Entire cohort 20 6,97 5,20 4,56 (1,73 - 19,50) < 0,001*
Length increase
Population Number Mean (cm) SD Median Range P-value
TPN PED 1 13 14,85 9,32 12,00 (3,00 - 32,50) 0,001
TPN PED 2 7 17,47 9,19 15,00 (8,70 - 32,50) 0,018
TPN PED 3 2 15,75 13,08 15,75 (6,50 - 25,00) 0,180
TPN PED 4 4 13,25 13,19 11,75 (0 - 29,50) 0,109
Entire cohort 20 19,99 16,44 12,75 (0 - 54,50) < 0,001*
Results 2008 - 2016Cohort 2 standard AIO admixtures
Effectiveness ~ growth
2) Evolution of BMI (> 2 years)
-> BMI-for-age z-scores
Higher positive evolution of BMI-for-age in standard AIO PN group (cohort 2)
Results 2008 - 2016Cohort 2 standard AIO admixtures
Safety – key findings
1) CRBSI & occlusion
Reduction in CRBSI and occlusion per 1000 HPN days with standard AIO admixtures
> 66 % CN Staph
Results 2008 - 2016Cohort 2 standard AIO admixtures
Safety – Key findings2) Metabolic complications (hypo-, hyper-)
- Higher frequency of electrolytes disturbances (Na+, K+, Ca2+, Mg+2, P) in tailored group versus standard PN group
eg. Na+ 28,6 % 7,7 %;
Ca2+ 35,4 % 16,2 %,…
- Most common electrolytes disturbances in standardized group
Hyperkalemia (16,4 %) 92,0 % caused by concomittant medicines or underlying disease
Hypomagnesemia (19.8 %) 90,9 % caused by concomittant medicines or underlying disease
Results 2008 - 2016Cohort 2 standard AIO admixtures
Safety – Key findings3) Parenteral nutrition associated liver disease (PNALD)
• Hepatocellular injury ~ AST , ALT > 2 months 1,5 X ULN
• Cholestasis ~ bili (direct – total), GGT, AP > 2 months 1,5 x ULN
• 8/21 patients never experienced abnormal LFT
• 10/21 patients transient episodes of abnormal LFT
- often related to CVC infection / immune related
- normalized by reduction of lipid intake
• 3/21 patients experienced longer periodes of abnormal LFT
- all 3 stable
- 1 patient (CIPOS) liver biopsy -> no presence of PNALD
Standard paediatric AIO PN admixtures
Safe & effective in HOSP en HOME care setting
In line with current new ESPGHAN/ESPEN guidelines 2018
Positive impact
• Manipulations and number of lines -> ↓ infection risk
• Resource efficiency
• Availability
• Time and cost
• Stability (longer shelf-life + additions)
Future perspective
- Standardized AIO PN admixtures NICU
Conclusion and Home take messages
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