None listed
Conditions
Brief summary
Parenteral nutrition (PN), consisting of carbohydrate, lipid, and amino acid constituent parts, is used in newborns when enteral feeding is insufficient. Those newborns requiring major surgery in the immediate postnatal period, comprising 17% of all late preterm and term newborns admitted to Australian NICUs per annum, are one such group with current supportive management emphasizing the importance of early nutrition. Recent data in children challenges this and suggests potential benefit from delayed provision of amino acids in the acute phase of a critical illness. The PEPaNIC (early vs late parenteral nutrition in the Paediatric ICU) RCT found that delaying PN (specifically amino acids) for a week following PICU admission reduced the length of admission by 30% and duration of ventilation by 40%, effects magnified on post-hoc analysis of the youngest patients. Confirmation of a similar response in ill surgical newborns is needed to drive practice change and improve both short- and longer-term clinical outcomes. Although the exact mechanism(s) remains unclear, the well newborn is exposed to a period of fasting for 48-72 hours following birth before the establishment of maternal milk supply, with fasting also a natural response to illness or surgical stress. Fasting results in up-regulation of autophagy which defines a phenotype of healing and repair, and which critically is suppressed by provision of amino acids. We hypothesize that delayed compared to early provision of the amino acid component of PN in late-preterm and term newborns requiring major surgery in the immediate neonatal period will shorten the duration of neonatal intensive care admission. The aim of this multi-centre, parallel group, superiority, blinded randomised controlled trial is to investigate the impact of delayed provision of the amino acid component of PN (intervention) versus early initiation (standard care) in late-preterm and term newborns requiring major surgery in the immediate newborn period on the duration of neonatal intensive care admission.
Interventions
10% Glucose + Heparin (days 1 and 2) then 10% Glucose + Heparin with electrolytes (days 3-7) plus 17% SMOFlipid® (Fish Oil-Rich in OMEGA-3 Acids, Medium Chain Triglycerides, Olive Oil, Soya Oil)/vitalipid fat emulsion will be provided to infants randomised to the intervention arm. The initial 10% Glucose + Heparin will contain 1U Heparin/ml. The total dose of heparin administered will be dependent on the volume of glucose required to maintain normoglycemia and appropriate electrolyte balance. Th
10% Glucose + Heparin (days 1 and 2) then 10% Glucose + Heparin with electrolytes (days 3-7) plus 17% SMOFlipid® (Fish Oil-Rich in OMEGA-3 Acids, Medium Chain Triglycerides, Olive Oil, Soya Oil)/vitalipid fat emulsion will be provided to infants randomised to the intervention arm. The initial 10% Glucose + Heparin will contain 1U Heparin/ml. The total dose of heparin administered will be dependent on the volume of glucose required to maintain normoglycemia and appropriate electrolyte balance. The 10% Glucose + Heparin and electrolytes will also contain 1U Heparin/ml in addition to Potassium 1mmol/50ml and 0.225% sodium chloride. Again, the total dose of heparin, potassium and sodium chloride administered will be dependent on the volume of glucose required to maintain normoglycemia and appropriate electrolyte balance. The 17% SMOFlipid®/Vitalipid will commence at 0.5 g/kg/day on day 1, increasing daily up to 3 g/kg/day. The 17% SMOFlipid® solution contains SMOFlipid 20% 36ml, Vitalipid N Infant 11.2ml and Soluvit N 2.8ml per 50 ml. For both groups the total fluid intake will commence at 45 mL/kg/day, increasing up to 150 mL/kg/day to maintain appropriate glucose and electrolyte balance. Each infant will receive their allocated nutritional intervention until postoperative day 7. Enteral feeds may commence at any time with the initiation and increase in volume as per centre practice with corresponding reduction in the administration of the 10% Glucose + Heparin with electrolytes solution as per normal nursery practice. The 10% Glucose + Heparin (days 1 and 2) then 10% Glucose + Heparin with electrolytes (days 3-7) plus 17% SMOFlipid® will be prescribed by the attending Neonatologist. Administration will be via peripheral central venous catheter as per normal clinical practice at the study site. Adherence to the allocated intervention will be achieved through daily audit of the participants medical records. From post-operative day 8 following the completion of the intervention period any participants still requiring parenteral nutrition will be prescribed standard total parenteral nutrition comprising 23g Amino Acid (as Primene) / 1000ml (Baxter 34 weeks to term parenteral nutrition as per 2022 Australia and New Zealand Neonatal Consensus Group PN Solutions) plus 17% SMOFlipid®/vitalipid fat emulsion. The Baxter 34 weeks to term parenteral nutrition solution contains Amino acid (as primene) 23g/l, Glucose 100g/l, Nitrogen 3.5g/l, Sodium 25 mmol/l, Potassium 20 mmmol/l, Magnesium 1.5 mmol/l, Calcium 9 mmol/l, Chloride 22.9 mmol/l, Phosphate 9 mmol/l, Acetate 8.5 mmol/l, Zinc 395.83 microgram/l, Heparin 500U/l, Paediatric Trace Elements 0.9 Units/l.
Sponsors
The University of Adelaide
Study design
Allocation
Randomised controlled trial
Intervention model
Parallel
Primary purpose
Prevention
Masking
Blinded (masking used) (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
All
Age
34 Weeks to 42 Weeks
Healthy volunteers
No
Inclusion criteria
Infants born >34 weeks gestation (inborn or outborn). Confirmation of a surgical diagnosis requiring operative intervention. The need for Parenteral nutrition. Informed parental consent.
Exclusion criteria
Expected death within 24 hours. Re-admission to NICU following previous randomisation.
Outcome results
None listed