Standard AIO Paediatric PN Clinical results zorgaanbod... · 2019-10-18 · Ideal weight class < 3...

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Standard AIO Paediatric PN Clinical results 5 e Symposium klinische farmacie UZ Gent 15-10-2019 De Cloet Joeri / Pharmacy Department

Transcript of Standard AIO Paediatric PN Clinical results zorgaanbod... · 2019-10-18 · Ideal weight class < 3...

Page 1: Standard AIO Paediatric PN Clinical results zorgaanbod... · 2019-10-18 · Ideal weight class < 3 Kg 3 kg –10 kg 11 kg –20 kg 21 kg –30 kg > 31 kg (- 18 year) Neonatal

Standard AIO Paediatric PN –Clinical results

5e Symposium klinische farmacie UZ Gent

15-10-2019

De Cloet Joeri / Pharmacy Department

Page 2: Standard AIO Paediatric PN Clinical results zorgaanbod... · 2019-10-18 · Ideal weight class < 3 Kg 3 kg –10 kg 11 kg –20 kg 21 kg –30 kg > 31 kg (- 18 year) Neonatal

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

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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)

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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.

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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

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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

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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

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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

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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

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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

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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

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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

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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

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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

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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

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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

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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

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• 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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Evaluation and follow-up paediatric patients

on HPN 2000 – 2016

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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*

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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)

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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

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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

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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

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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