Guidelines for the Prescribing and Administration of Parenteral Nutrition (PN) for Children on Paediatric Intensive Care (PICU)

• Summary
• Aim
• Background
• Guidance of when and how to prescribe PN
• Appendix 1 Continuous infusion, maximum drug concentrations in use at LTH PICU
• Appendix 2 FOR NURSING STAFF: Checking of PN
• Appendix 3 FOR NURSING STAFF: Checking of Numeta G13/G16/G19 and Omeflex Plus 1875

Summary

Guideline for the Prescribing and Administration of Parenteral Nutrition (PN) for Children on Paediatric Intensive Care (PICU).  This document should be used in conjunction with the guideline for the Administration of Parenteral Nutrition (PN) to neonates, infants and children and the Guidelines for the Management of Paediatric Patients at Risk of Refeeding Syndrome.  This document provides guidance regarding when to decide that PN is required, the referral pathway, and prescribing and administration guideline for children on PICU.

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Aim

This guideline aims to give the multidisciplinary team (doctors, nurses, pharmacists and dietitians) a source of information and advice on when and how to prescribe PN for children on PICU.  This is to enable a provision of a high quality PN service to children on PICU where oral or enteral feeding is not a viable option.

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Background

There are many factors which effect when a child should receive PN on PICU and how much nutrition should be provided.  The phases of critical illness plays a role in deciding when PN should be started, the energy requirement for a child and hence the amount of nutrition they receive.  Also the nutritional status / history of the child plays a role and must be carefully assessed.

A recent large international multi-centred randomised controlled trial (PEPaNIC) in 1440 critically ill children found late onset PN (started on Day 8 of PICU admission) was clinically superior to the early initiation of supplemental PN (initiated within 24 h after PICU admission).  There were significant issues with the study in terms of heterogeneity of the paediatric population, PN starting without strict indication, glucose management differences across centres and caloric overfeeding in the early PN group.  However the study did show that early PN on PICU had increased risk of infections, time on the ventilator, kidney failure and increased length of stay on PICU, as well as there being minimal difference in a number of nutritional markers on discharge from PICU between the two groups.

Research has highlighted that where possible the enteral route for feeding should be used, and PN can be delayed to give further opportunity for enteral feeding in certain situations.

Enteral feeding should always be the route of choice as it is safer in terms of mechanical, septic and metabolic complications.

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Guidance of when and how to prescribe PN

Referral Pathway

The decision to initiate PN must be made by a senior clinician in conjunction with a pharmacist and Dietitian when available.  A referral form must be completed by a doctor and approved by a PN pharmacist before PN will be made.

Before PN is started please ensure:

1. A line is available, ideally central line
2. PN baseline bloods have been completed, see Administration of Parenteral Nutrition (PN) to neonates, infants and children

When and how to prescribe PN

The aim of PN on PICU is to provide sufficient calories and protein to a child to maintain their weight and nutritional status, if enteral nutrition has failed.
Note: It should not be used to achieve catch up growth, unless a patient has been in the recovery phase for a sufficient period of time.

STEP 1
Ensure the child cannot get adequate nutrition from enteral feeding. 

STEP 2   
Assess the child to see which phase of the critical illness they are in:

The target nutritional needs will be determined by a Dietetic assessment, considering the child’s clinical status and nutritional history.  The table above works as a guide for nutritional requirements, however adjustments may be needed in children on renal replacement therapy (RRT), extracorporeal membrane oxygenation (ECMO), with a high urea, high conjugated bilirubin, high blood sugars, high triglycerides and other clinical issues.  It is therefore important to have regular dietetic input to ensure appropriate target requirements are in place, reflective of the current clinical picture.

When converting calories from enteral nutrition to PN, then a 10 % reduction is applied to account for diet induced thermogenesis  i.e. 90% of enteral calories = 100% of PN calories ²

STEP 3
The children are then categorised into risk factors:

STEP 4

Prescribing PN
The format of this guidance follows the systematic approach of the prescription.

Access
Ideally the PN should be run down a central line.  If there is central access then other medicines should be moved to allow this to happen.  If necessary check compatibility of medicines using the PICU compatibility chart  medusa or medicine information, but ideally no other medication should be run with the PN.  Very rarely peripheral PN should be given.  PN has a high osmolality and there is a very high risk of extravasation, so peripheral PN is not advised in patients who are peripherally shutdown or have cardiac conditions.  It is also difficult to achieve adequate nutritional intake via a peripheral line.  The maximum glucose concentration allowed on PICU down a central line is 30% and 10% for a peripheral line.

Weight
Always use the working weight in Kg.  This may be different from the actual weight as the child may be oedematous or the child may be clinically overweight.  If the child is overweight then an ideal weight based on height should be used.  Children on PICU should be weighed at least one a week so a nutritional assessment can be done.

PN infusion rate
PN should be given over 24hours in PICU patients to allow time to metabolise carbohydrates and to keep a constant fluid rate.  If there is lack of line time the PN infusion may need to be stopped and started and thereby run over less than 24 hours.  If this is the case the PN infusion rate does not need to be halved to stop hypoglycaemia.

Nutrition

Nitrogen (g/Kg/day)-
Guidance on the paediatric/neonatal PN charts will support with nitrogen source selection and initial incremental nitrogen increases. The target for nitrogen will be advised by a dietitian based on their dietetic assessment. Meeting the nutritional target is not always possible due to volume restrictions and often “best fits” will need to be done.  These “best fits” should aim to provide a minimum nitrogen intake of 0.24g/kg/day from birth- 1 month and 0.16g/kg/day from 1 month onwards to avoid a negative nitrogen balance ^{3 5}.

There is currently no evidence that exceeding nitrogen intakes of 0.48g/kg/day in term infants ^{6 7} and 0.56g/kg/day in pre-term infants is beneficial³. This guidance does not however consider additional nitrogen losses i.e. loss of serous fluid, RRT.

Carbohydrates (g/Kg/day)
Initial carbohydrate provision can be guided by calculating the amount of glucose the child is receiving in the maintenance fluid running (g/Kg/day).  Increase carbohydrate in 2g/kg increments daily up to the nutritional target as advised by a dietitian. Generally a carbohydrate intake of 50-75% of non-protein calorie intake is recommended.

Overfeeding/excess glucose load occurs when parenteral glucose delivery exceeds the rate of glucose oxidation, which can have a detrimental effect on the clinical status of a patient^{9 10}. Signs of over-feeding may include hyperglycaemia, leading to increased lipogenesis, fat deposition ¹¹ and liver steatosis ¹². It may also be noted with dyslipidaemia, increased carbon dioxide levels and ventilation requirements ^{13- 15}.

In order to prevent over-feeding, carbohydrate levels should not routinely exceed the following upper limits:

Lipid (g/Kg/day)
Increase the fat in PN as per PN regimes.  As fat is the most calorie dense nutrient, there is a benefit on increasing the fat content in volume restricted patients. Generally, a lipid intake of 25-50% of non-protein calorie intake is recommended ¹⁸. Fat intakes should not exceed 3g/kg/day for infants and children at LTHT due to the licencing of product used, however in certain situations evidence shows that infants may tolerate up to 4g/kg/day with no negative impacts ^{18 19} . Patients on critical care may suffer from parenteral nutrition associated cholestasis.  This may be identified from high bilirubin levels showing a large proportion of conjugated bilirubin. Options to help reverse this condition may include reducing the fat content of the PN and consideration for trophic enteral feeding. ^{23 24}.

Triglyceride Levels
Dyslipidaemia in the form of high triglyceride levels may also be seen in critical illness ^20-22. This can be further exacerbated by excess fat and glucose intakes ¹⁶. If levels are >3mmol/L in infants or 4.5 mmol/L in children consider reducing the fat content of the PN (not stopping totally) ¹⁸. Triglyceride levels should be checked before commencing PN, and then repeated weekly. If fat intake has been reduced but high triglyceride levels continue, this may suggest carbohydrate excess intake rather than fat excess intakes, but may also reflect non-nutritive related hypertriglyceridaemia.

Prescribing PN for children with Metabolic Disorders
For children with metabolic conditions ensure the consultant on call has discussed the patient with the Manchester Children’s Hospital metabolic department. For advice on nitrogen, carbohydrate and lipid allowances contact the lead PICU Dietitian, or directly liaise with the Manchester Metabolic Team on evening/weekends.  It is important that changes of these allowances are only done in conjunction with the metabolic team.

Fluid and electrolytes

The total fluid the child is receiving is referred to as a percentage of the intravenous fluid requirements.  This total fluid will need to include enteral feeds, drug infusions and intermittent drug infusions. 

Enteral feeds
Enteral nutrition should only be included in the total fluids when they are established and being absorbed i.e. the child is not getting large aspirates.  Enteral nutrition on PICU is usually given continuously.

Drug infusions
Only include continuous drug infusions, including continuous flushes for arterial and CVP lines and intermittent drug infusions.  Intravenous drug boluses and intermittent intravenous flushes are not included in any circumstances.

If there is inadequate fluid to start PN or to increase the nutrition of the PN as per the instructions on the PN chart, then firstly the drug infusions and intermittent infusions should be concentrated where possible.  See appendix 1 for information on concentrating drugs.  Once this is done then it is important to check with the PICU consultant if the total fluid allowance can be increased to allow adequate nutrition.

Electrolytes

Before initiating PN calculate the amount of electrolytes the child is receiving via intravenous (IV) maintenance fluids and electrolyte replacements.  Also useful to calculate the amount of carbohydrate they are getting from the maintenance fluid.

Sodium (mmol/Kg/day): The amount of sodium the child is receiving from IV maintenance fluid will give you a guide of how much to place in the PN.  Increase or decrease the amount of sodium by 1 to 3mmol/Kg/day as necessary.  Double check there is no changes in medications that could potentially affect the sodium levels i.e. Sodium bicarbonate infusion stopping, starting foscarnet. 

It is important to make sure there is not drastic changes in sodium blood levels each day (increasing or decreasing by 10mmol per day), as this can result in cerebral oedema or demyelination.

There are clinical indications when higher sodium plasma levels are required, greater than 150mmol/L i.e. for cerebral protection/head injury.  This should be documented on the PN chart.

Potassium (mmol/Kg/day): The amount of potassium the child is receiving from IV maintenance fluid and potassium replacements will give you a guide of how much to place in the PN.  Increase or decrease the amount of potassium by 0.5 to 1mmol/Kg/day as necessary. The amount of potassium prescribed needs to take into account the child’s clinical status such as urinary output, renal function, post-cardiac surgery, arrhythmias etc.

Calcium (mmol/Kg/day): Check the amount of calcium replacement the child has received over the last 24hours; this should give you a guide of how much to place in the PN.  Check the level of calcium in the blood by looking at the ionised calcium on the blood gases.  The ionised calcium should routinely be above 1.  If the child is having arrhythmias then higher ionised calcium levels are aimed for.

Magnesium (mmol/Kg/day): Check the amount of magnesium replacement the child has received over the last 24hours; this should give you a guide of how much to place in the PN.  If the child has a cardiac condition or/and is having arrhythmias then higher magnesium level are usually required i.e. post cardiac surgery above 0.8mmol/L and for arrhythmias around 1mmol/L.  If magnesium level is appropriate start at 0.2mmol/Kg/day

Phosphate (mmol/kg/day): Check the amount of phosphate replacement the child has received over the last 24hours; this should give you a guide of how much to place in the PN.  The amount of phosphate prescribed needs to take into account the child’s clinical status such as urinary output, renal function, if they are on CVVHD and if they have high levels after cardiac surgery.

Vitamins / Trace Elements
Follow PN prescriptions for guidance on how to prescribe Peditrace/Additrace, Solivito and Vitlipid infants/adults.

Administration of PN (see appendix 2 and 3)

Administer the PN as prescribed; the infusion rate will be on the labels of the PN. 

If there is a change in the clinical state of the child, drug infusion rates or the volume of drugs administered for the child then follow the following guidance:

• If the constituents of the PN are no longer appropriate, then stop the PN and replace with maintenance fluid.  Never add anything to the PN.
• If the child is not receiving enough volume, then administer glucose 5% to make up to the necessary volume. 
• If the child is receiving too much volume, reduce the rate of the vamin or Numeta bag appropriately.  Please note by doing this the amount of electrolytes the child will receive will reduce.

If there is a change in the child’s enteral nutrition rates, then follow the following guidance:

• If the child is not receiving enough volume from their enteral nutrition and PN, then administer glucose 5% to make up to the necessary volume. 
• If the child is receiving too much volume, reduce the rate of the vamin or Numeta bag appropriately.  Continue to reduce the vamin/Numeta bag rate as the enteral nutrition increases.  

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Appendix 1 Continuous infusion, maximum drug concentrations in use at LTH PICU

Please do not recommend concentrating drug infusions without talking to the nurse in charge and the doctor first.

Please note

• For children 16Kg and under, PICU would routinely double or quadruple infusion up to the maximum routine concentrations.  
• The usual minimum infusion rate for infusions is 0.2mL/hour, however in small patients, it may not be possible to provide the correct dose if the infusion is over concentrated.
• It is important to note that with inotropes and other drugs with short half-lives that you may need to use more dilute infusions and/or higher infusion rates, to prevent fluctuations in blood pressure as you increase/decrease the dose.

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Appendix 2 FOR NURSING STAFF: Checking of PN

PN needs to have been out of the fridge for 4 hours before IV administration to allow it to reach room temperature and so that we are using the same practice across the Trust. However if it reaches room temperature before this it can be given to the patient.

When double checking PN with another registered nurse, using the white “Details of Paediatric Parenteral Nutrition” firstly check:

	Correct patient, unit number and date of birth against wristband Correct weight (adjusted may be used) Above details match the printed labels on the vamin/lipid
To check the correct constituents of the PN, you use the bottom middle column (highlighted below) of the white printed “Details of Paediatric Parenteral Nutrition ” titled Major Constituents” and check the per kilogram amounts are the same (you do not have to calculate them) against the PN prescription (green/pink chart) for:
	Nitrogen Glucose (carbohydrate) Fat Electrolytes (sodium & potassium) Minerals (calcium, magnesium, phosphate) Final glucose concentration

To check the labels:

• Check biographical details and expiry
• Check labels for the vamin and lipid are attached to the correct bag
• Check the route of administration (peripheral or central) on the label against the PN prescription
• Check the rates are correct taking into account if a patient is fluid restricted.

Write down the pump number, batch number, sign the prescription sheet-adding a time is useful.

N.B Lipid lines need changing 24 hourly and vamin lines 72 hourly so please label accordingly

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Appendix 3 FOR NURSING STAFF: Checking of Numeta G13/G16/G19 and Omeflex Plus 1875

PN standardisation is being introduced in all the paediatric wards at LTHT. It has already been introduced on NNU, L51 and PICU wards in 2019 without any issues.

The PN prescription will be prescribed on a pink Neonate PN prescription (even if the child is not a neonate).

There are 4 standard bags available and the PN pharmacist will decide which bag to use depending on the weight of the patient, see below:
Numeta G13 for patient <2.5kg
Numeta G16 for patients 2.5-5kg
Numeta G19 for patients 5-20kg
Omeflex Plus 1875 for patients 20-40kg

Numeta and Omeflex are concentrated single bag (fat, nitrogen and glucose source all in one) that needs to be given centrally. The PN bag might not provide the full amount of fluid that a patient requires per day; therefore top up IVF might need to run alongside the PN. 5% glucose should be used first line as IVF top up, but other fluids can be used depending on patient requirements.

All standard PN bags should be protected from light during administration and filtered using a 1.2micron filter.

PN needs to have been out of the fridge for 4 hours before IV administration to allow it to reach room temperature and so this is in line with practice across the Children’s Hospital. However if it reaches room temperature before this it can be given to the patient.

When double checking PN with another registered nurse, using the white “Details of Paediatric Parenteral Nutrition” firstly check:

• Correct patient, unit number and date of birth against wristband

To check the correct volumes/constituents of the Numeta and Omeflex PN as the same form details sheet to pink PN prescription chart.

• Check correct route, should be central for standard bags
• Check the volume per Kg of the Numeta or Omeflex; this comes under the title “For Paediatric Multichamber bags containing regimens ONLY”
• Check the volume for PN in the “Major Constituents” section.
• No additional electrolytes can be added to a Numeta G16, G19 or Omeflex therefore the electrolytes do not need checking for these bags.
• Check final glucose concentration is less than the maximum on the PN chart.

To check the labels:

• Check biographical details and expiry
• Check labels for the Numeta or Omeflex  are attached to the bag
• Check the rates.

Complete Administration record, sign the PN prescription chart and confirm the pump rate is correct