Nottingham Neonatal Service Clinical Guideline

Transcription

1 Nottingham Neonatal Service Clinical Guideline D6 Title of Guideline: Author: Contact name and job title Directorate & Speciality: Date of submission July 2017 Explicit definition of patient group to which it applies (e.g. inclusion and exclusion criteria, diagnosis): D6 Neonatal Parenteral Nutrition (PN) Chris Jarvis, Specialist Neonatal Dietitian Amy-Jo Hooley, Paediatric PN Pharmacist Helen Budge, Professor of Neonatal Medicine Shalini Ojha, Clinical Associate Professor, University of Nottingham Family Health - Neonatology Infants admitted to Neonatal Unit who meet the indications in Section 1.1 Version 10 If this version supersedes another clinical guideline Replaces V9 main changes: please be explicit about which version it replaces (not Simplify prescription charts applicable if this is a new guideline, enter below if extensive): Prescription charts printed as per Trust MMC recommendation Removal of peripheral PN regimen Modification to Bespoke regimens to ensure safer prescribing (Section 4.3) Statement of the evidence base of the guideline has the guideline been peer reviewed by colleagues? 1 NICE Guidance, Royal College Guideline, SIGN (please state source) 2a Meta-analysis of randomised controlled trials 2b At least one randomised controlled trial 3a At least one well-designed controlled study without randomisation 3b At least one other type of well-designed quasiexperimental study 4 Well-designed non-experimental descriptive studies (ie comparative/correlation and case studies) 5 Expert committee reports or opinions and/or clinical experience of respected authorities 6 Recommended best practise based on the clinical experience of the guideline developer Reduce early poor nutritional intake to improve growth and neurodevelopment 2a, 2b, 4 Use of acetate to reduce chloride load and provide nonmetabolisable base 2b Whole guideline 5, 6 Consultation Process Ratified by: Date: Target Audience Review Date: (to be applied by the Integrated Governance Team) A review date of 5 years will be applied by the Trust. Directorates can choose to apply a shorter review date; however this must be managed through directorate Governance processes. Circulation to Staff of Neonatal Service Nottingham Neonatal Service Guideline Task and Finish Group July 2017 Staff of the Nottingham Neonatal Service, Paediatric wards and PICU July 2022 This guideline has been registered with NUH Trust. However, clinical guidelines are guidelines only. The interpretation and application of clinical guidelines will remain the responsibility of the individual clinician. If in doubt contact a senior colleague or expert. Caution is advised when using guidelines after the review date or outside of the Trust.

2 Nottingham Neonatal Service Clinical Guideline D6 KEY POINTS Minimise delay between birth and optimising nutrition where full enteral feeds are not likely within 5 days. At birth: o <30w gestation ensure Starter Preterm as soon as central access is achieved via UVC o >30w if Starter Preterm not appropriate, and PN likely to be necessary, order from pharmacy, using 10% dextrose in the short term Prescribe Tailored PN with minimum changes Na, K, Ca & P are the only nutrients that can be increased within the stability matrix shown (Table 1) No components of Tailored PN can be decreased due to bulk manufacture of Standard Regimens Bespoke prescribing is possible to allow decrease of nutrients, fluid, etc. Consultant input is mandatory, preferably in conjunction with neonatal dietitian and/or paediatric PN pharmacist. A series of Bespoke regimens are available with a guidance for prescribing (Section 4.3 and Appendices 6 & 6A) Basic Stock PN is available in the fridge on the Neonatal Units as Stock Preterm and Stock Term regimens only. Guidance for use is given in Section 4.4 Composition of regimens, recommended use and detailed nutritional profile is available as an A4 summary (Appendices 1&2) with prescribing guidance on back of every prescription List of Appendices APPENDICES 1&2 - Summary NICU D6 PN Regimens + Detailed Nutritional Profile APPENDIX 3 - Starter Preterm Prescription (printed on white) APPENDIX 4 - Starter Preterm Re-Order Sheet APPENDIX 5 - Standard Tailored PN Prescription APPENDIX 6 - Bespoke PN Prescription (printed on lilac paper) APPENDIX 6a - Guide to Bespoke Prescribing APPENDIX 7 - Basic Stock PN Prescription and Prescribing Guide Preterm printed on blue, Term on pink APPENDIX 8 - Basic Stock PN Re-Order Sheet APPENDIX 9 - Example SPU PN Printout + bag labels (for nurse checking) APPENDIX 10 - Nursing Chart for Recording PN Rate Changes 2

3 Nottingham Neonatal Service Clinical Guideline D6 1. Background Few people dispute that the aim of nutrient provision for infants born at the extremes of prematurity should be to achieve the growth rate seen in utero at the equivalent gestation. [1] However, infants born prematurely often fail to achieve this and a number of studies have shown that significant nutritional deficits occur in the first few weeks following premature delivery. [2, 3] Variation in nutritional practices, especially those practices concerned with the initiation and advancement of parenteral and enteral nutrition, largely explain these differences in growth. [2] A link between poor growth and long term neurodevelopmental outcome has also been described. [4] The evidence available suggests early administration of both parenteral and enteral nutrition to reduce losses due to catabolism and minimise nutritional deficits. This should be by provision of early adequate protein as intravenous amino acids along with glucose and lipid and early maternal expressed breast milk as soon as it is available and likely to be tolerated. [5] This provision of adequate PN allows for maintenance of optimum nutrition while enteral feeds are established. 1.1 Indications for parenteral nutrition (PN) Extremely preterm (<30 weeks) or low birth weight infants (<1250g) are severely nutritionally compromised and should usually receive PN Infants born at 30 weeks or above who are unable to establish significant volumes of enteral feed by 5 days either through illness (e.g. RDS, necrotising enterocolitis), immaturity or anomaly of the gastrointestinal system should receive PN In addition, PN may be recommended for babies with severe intrauterine growth restriction (IUGR) with absent or reversed end diastolic flow. Rapid introduction of full enteral nutrition may not be in their best interests, and the resulting reduction in volumes of enteral nutrition renders them at risk of prolonged sub-optimal nutrition and poor growth. 1.2 Cautions in the use of parenteral nutrition (PN) Enteral feeding is required for the maturation of enzymes, absorptive transport systems and the secretion of gut hormones that control motility. Consequently, in most instances, PN will be supportive whilst enteral nutrition is established PN may sometimes need to be avoided whilst any severe metabolic upset is stabilised PN must be prescribed carefully and its contribution to each infant s nutritional intake assessed regularly and carefully by the attending clinical team. 2. Aims of PN Administration To provide amino acids and glucose from birth [6] and lipid before 48 hours To achieve full nutritional requirements, in combination with enteral feeding [7] To maintain optimum growth and development To monitor tolerance and recognise situations where PN administration is disadvantageous 3. Nutritional Components The main nutritional components of Starter and Standard PN Regimens are given below with maximum suggested for tailoring in brackets. Prescribing above the maximum given may be possible following a telephone request to pharmacy production staff to obtain stability confirmation from the manufacturer. Such amendments to the intended standard regimens always need to be discussed with the NICU Duty Consultant who must countersign the prescription. This service is not available at weekends. 3

4 Nottingham Neonatal Service Clinical Guideline D6 Table 1: Nutritional Composition of Standard Tailored Regimens (standard amounts are shown with any agreed additions given in brackets) Regimen Starter Preterm PN (Aqueous only) Standard Tailored Preterm PN Standard Tailored Term PN Administration Central Central Central Volume ml/kg/day (~120 with lipid) (~120 with lipid) Nitrogen g/kg/day Protein g/kg/day Glucose g/kg/day Sodium mmol/kg/day ( max 15) 3 (max 15) Potassium mmol/kg/day (max 5) 2.5 (max 5) Calcium mmol/kg/day (max 2.5) 1.0 (max 2.5) Magnesium mmol/kg/day Phosphate mmol/kg/day 1.0 *2.0 (max 2.5) *1.0 (max 2.25) Acetate mmol/kg/day Fat (lipid) g/kg/day - 2 then 3 (0.5-3) 3 (0.5-3) Energy (total) kcal/kg/day (2g fat), 104(3g fat) 100 *some phosphate provided by lipid so phosphate delivered will be slightly less when <3g fat/kg/day is given. Trace elements and vitamins will be added to all PN (except Preterm Starter) unless requested otherwise. 3.1 Protein/Amino Acids/Nitrogen (N) Aminoven Infant 10% TM is an amino acid solution specifically formulated to meet the protein requirements of neonates and infants, with a profile based on human milk protein. It contains 52% essential amino acids, other amino acids which are conditionally essential to neonates and preterm infants and a well-balanced pattern of non-essential amino acids. It is also a source of acetate. 3.2 Energy Non-nitrogen energy is provided by glucose alone in the Starter Preterm regimen and glucose and fat (lipid) in an energy ratio of approximately 2:1 in both Preterm and Term regimens. This ratio has been shown to promote good nitrogen retention.[8] Increasing carbohydrate and/or fat could provide more energy if required but advice must be taken from Neonatal Dietitian or Neonatal PN Pharmacist. 3.3 Carbohydrate Glucose intake increases as the administered volume increases. Starter Preterm contains 15% glucose and Preterm and Term aqueous bags approximately 15% glucose (depending on the final volume if additional electrolytes are prescribed). As the %glucose given applies only to the aqueous bag, the overall % received by the baby will be lower due to lipid increasing the final volume of PN delivered. 3.4 Fat Intralipid 20% TM is the standard isotonic fat emulsion used, and is a concentrated source of energy and essential fatty acids (EFA) in PN. Occasionally, infants requiring long term PN, or who have a conjugated bilirubin >50umol/l, may receive SMOF lipid following discussion between the Neonatal Dietitian, Attending NICU Consultant and Pharmacy SPU. SMOF is a blend of soya, MCT, olive and fish oils and it may have a role in preventing, or reversing, cholestatic jaundice [9] although there is not yet consensus on any benefit.[10] 4

5 Nottingham Neonatal Service Clinical Guideline D6 The maximum amount of fat tolerated by preterm infants is difficult to determine. Levels up to 3g/kg/day have been shown to be tolerated when infused over 24 hours [11, 12]. Occasionally up to 4g fat/kg/day may be required following dietetic advice. When 4g fat/kg/day is given, serum triglycerides should be monitored until tolerance is seen. The benefits of routine monitoring of triglycerides are not established, so this is not routinely undertaken. However, if a blood sample is visually lipaemic, serum triglyceride should be checked every 24 hours until tolerance is achieved. The following guide may be useful, though change in plasma triglyceride concentration may be a better indicator of tolerance than the actual level as large increases are likely to reflect lipoprotein lipase saturation. Triglyceride level <2.8mmol/l Action recommended - current lipid prescription continued 2.8 4mmol/l - current lipid prescription reduced from 3g 2g/kg/day or from 2g1g/kg/day and re-check in 24 hours >4mmol/l 3.5 Electrolytes - current lipid prescription reduced to 0.5g/kg/day to ensure some EFA and vitamins are delivered and re-check in 24 hours Adapted from [13-15]. Standard PN bags are pre-manufactured and the minimum nutrient levels shown in Table 1. Sick, preterm infants will have differing needs so a matrix has been agreed that allows prescription of more sodium, potassium, calcium and phosphate. Additions to the PN provided can be made by Pharmacy SPU only and under no circumstances should the Neonatal team or others amend or add to the aqueous or lipid components of PN. Although serum electrolyte measurements may need to be performed daily, it is not usually necessary, or in fact helpful, to alter prescriptions daily. The following should be considered before changing the sodium or potassium prescription:- - how long has any previous change been in effect? - what is the trend or serial change in electrolytes rather than individual results? - are there other factors e.g. excess fluid losses or sodium from drug infusions? - making gradual rather than large changes to avoid peaks and troughs If in doubt, discuss alterations with the NICU Attending Consultant Sodium (Na) Starter Preterm Regimen does not contain sodium in order to aid physiological postnatal diuresis. The Tailored Preterm Regimen contains a minimum of 3.5mmol sodium/kg/day and the Tailored Term Regimen contains a minimum of 3 mmol sodium/kg/day. Hypernatraemia is not usually caused by excessive sodium intake but by inadequate hydration and through excessive water losses. In such cases, fluid administration should be increased. Sodium may need to be increased when sodium losses are high. Hyponatraemia may also be caused by use of excessively dilute fluid, inappropriate ADH (rarely) and excessive bowel losses. Regimens have solution stability up to 15 mmol Na/kg, though more may be possible following SPU agreement on stability. Sodium intake is increased beyond the standard amounts in the regimens by using sodium chloride and so will increase chloride load. 5

6 Nottingham Neonatal Service Clinical Guideline D Potassium (K) Starter Preterm PN contains 1mmol/100ml aqueous solution in order to provide some phosphate. In all PN Regimens, the standard potassium is 2.5mmol/kg/day provided by potassium acetate in the Preterm Regimen to reduce acidosis [16] and potassium chloride in the Term Regimen. Additional potassium prescribed to individual babies as part of these Tailored Regimens will be provided as potassium chloride. Regimens have been tested for stability from 2.5-5mmol/kg/day. Therefore, if >5 mmol/kg/day is considered, whether this is required or appropriate should be discussed with the NICU Attending Consultant and then stability should be sought from Pharmacy. If potassium is increased above 5mmol/kg/day, ECG monitoring is necessary. 3.6 Minerals Calcium (Ca) & Phosphate (PO 4 ) Preterm Term Calcium gluconate 10% 2.0mmol Ca/kg 1.0mmol Sodium glycerophosphate 21.6% 2.0mmol PO 4 /kg 1.0mmol The ideal weight ratio of calcium to phosphate is thought to be between 1-1.5mg : 1mg [17]. Our molar ratio of 1:1 is equivalent to a weight ratio of 1.3:1. It is important when Ca or PO 4 are modified from standard, or their ratio is altered, to increase monitoring. Although higher amounts of these minerals may be possible, more than 2.5mmol Ca and PO 4 are rarely needed and should be discussed with the Neonatal Consultant, Neonatal Dietitian and/or Neonatal PN Pharmacist. Total calcium intakes over 8.8mmol/day are not advised [18]. A short term fall soon after birth is common so, before increasing Ca or PO 4 in the PN prescription, consideration should be given to a) the current plasma concentration b) the preceding intake especially soon after birth where intake may have been suboptimal c) achieving intended volume of PN to ensure adequate intake. However, if serum phosphate stays below 1.2mmol/l, PO 4 in PN should be increased and monitoring of Ca, PO 4 and alkaline phosphatase performed twice weekly to maintain serum PO 4 >1.5mmol/l. NB When increasing phosphate, an increase in PN sodium is usually required as sodium glycerophosphate is used as the phosphate source. Therefore, for every 0.5mmol/kg/day increase in phosphate, it is usually necessary to increase the sodium by 1mmol/kg/day Trace Minerals A full range of trace minerals and electrolytes are added to give more complete nutrition. The trace mineral solution, Peditrace TM, is routinely added along with 0.2mmol Mg as magnesium sulphate. Although the manufacturers recommend that Peditrace should not be added until renal function is established, this is rarely an issue in neonatal practice. Iron is not present in Peditrace and is not routinely added to neonatal PN. After 1 month of PN administration, iron may be required and 100micrograms/kg/day can be added. This must be discussed with the Neonatal Consultant, Neonatal Dietitian and Neonatal PN Pharmacist and requested in the Other box on the PN prescription. Patients requiring long term PN (>1 month) should have blood taken for estimation of: + zinc + copper + selenium + manganese [19, 20]. Abnormal results and subsequent management should be discussed with the Neonatal Dietitian and Neonatal PN Pharmacist. 3.7 Vitamins Water soluble and fat-soluble vitamins are added to lipid for all regimens Solivito N TM 1/10 th vial per kg/day and Vitlipid N Infant TM 4ml/kg/day 6

7 Nottingham Neonatal Service Clinical Guideline D6 4 Management of infants requiring parenteral nutrition 4.1 Prescribing Standard Neonatal Regimens A summary of PN Regimens, their use and nutritional composition is available (Appendices 1&2) Preterm Infants less than 34 weeks Infants born at less than 30 completed weeks, or weighing less than 1.250g, should be routinely started on Starter Preterm Regimen PN as soon as a central line is present. Infants >30w or >1250g who need PN may also receive Starter Preterm. If a UVC has been sited and blood can be aspirated from it at insertion, Starter PN (which does not contain lipid) may be connected to the UVC whilst the confirmatory X-ray is undertaken and reviewed. Connecting 10% dextrose to the UVC in these circumstances is unnecessary. If a percutaneous longline has been sited for the administration of PN, a confirmatory X-ray should be obtained before commencement of PN. If a central line cannot be secured, 10% dextrose should be commenced through a peripheral line. Starter Preterm Regimen PN is available ready-made in 200ml bags on the Neonatal Intensive Care Unit and has a 90 day shelf life. Lipid is not currently infused with Starter Preterm. The giving set and associated lines must be changed by 48 hours and any PN remaining must be discarded. Most babies should have been prescribed and be receiving Tailored Preterm PN by hours of age. Each Starter PN bag comes with a prescription sheet (Appendix 3) which must be completed by the doctor prescribing the required volume/kg/day and a re-order sheet (Appendix 4) returned/faxed to Pharmacy SPU by nursing staff with daily prescriptions in order to maintain stock levels. The flow rates will be calculated by the nursing staff, checked and signed. No additions can be made to Starter Preterm PN. Starter Preterm PN contains 15% dextrose. Volumes up to 80ml/kg/day (8.3mg glucose/kg/min) are usual. However, up to 100ml/kg/day (10.4mg glucose/kg/min) can be prescribed providing tolerance is assured by regular measurement of blood glucose. Volumes >80ml/kg/day may not well tolerated in sick preterm infants when any additional volume should be given as 5% dextrose. Standard Tailored Preterm PN Regimens should be prescribed using a Standard PN Prescription Chart (Appendix 5). The prescription should be written in the appropriate daily column for each baby until they are stable on the full regimen when prescriptions can be written for 48 hours. No PN is manufactured on Saturdays and there is a limited service on Sundays. Therefore, where possible, PN should be prescribed on Thursday for use Thursday and Friday, and on Friday for use Saturday and Sunday. Two 24 hour bags may be prescribed instead of one 48 hour bag i.e. the two days prescriptions do not have to be the same. This is important to consider if the infant s requirements are expected to change within the 48 hour period or a change of line is anticipated. When using these Tailored Neonatal PN Regimens, the amounts cannot be reduced but additional sodium, potassium, calcium and phosphate within a stability matrix are possible. All regimens have been tested for physical stability with additions within an agreed stability matrix shown for each nutrient in brackets after the standard amount (Table 1). Prescribing outside the Regimen matrix may be possible but needs careful consideration and discussion with the Attending NICU Consultant, Neonatal Dietitian or Neonatal PN Pharmacist and Pharmacy SPU. As it will be necessary to obtain stability data from an external source, this should be done as early in the day as possible and is not available at weekends. Max must never be written as SPU will only provide the specified matrix maximum. If you require more than specified matrix maximum speak to SPU staff before prescribing. If there is poor glucose tolerance with PN Regimens at the volumes prescribed, infusion rates may be reduced temporarily and fluids replaced with 5% dextrose in the short term. However, the cause of the glucose intolerance should be sought (including evidence for sepsis). As nutrition is of great importance, appropriate consideration should be given to the use of insulin where glucose intolerance is present (Section 5.3). 7

8 Nottingham Neonatal Service Clinical Guideline D Near-term and Term infants born at or above 34 weeks gestation Infants born at, or above, 34 weeks gestational age can receive 10% dextrose whilst Tailored Term Regimen PN is ordered. However, consideration of the use of Basic Stock PN should be given when infants are admitted after the Friday PN prescription deadline as Tailored PN will not, thereafter, be available until a Sunday PN prescription. Once Tailored Term Regimen PN is available from Pharmacy SPU, parenteral nutrition is increased as the daily fluid allowance increases. In general, infants born prior to 34 weeks gestational age will not change to Term PN if they still require PN when they reach a corrected gestational age of 34 weeks as their requirements are still likely to be higher than babies born at this gestation. Individual circumstances should be discussed with the Neonatal Dietitian. 4.2 Flow rates Neonatal PN is presented as 2 separate solutions: - an AQUEOUS bag containing protein, glucose, electrolytes and minerals and a lipid syringe/bag of fat and vitamins. The aqueous bag can hang for 48 hours - a LIPID syringe or bag which must be changed every 24hours. Therefore, 2 syringes will be sent with a single 48hr prescription PN. A detailed print-out of the solutions will accompany the PN with suggested flow rates on the labels (Appendix 9). These are used by the nursing staff for checking against the prescription. Any reduction in volume to that prescribed must be made proportionately to both solutions. For example, if PN was prescribed in 120ml/kg/day but only 100ml/kg/day is to be given, the flow rate figures for both aqueous and lipid solutions should be multiplied by 100 divided by 120. NB: As the final volume will not be exactly 120ml due to added electrolytes or bone minerals, the fluid volume given on the SPU printout, should be used in these calculations /48 hour prescriptions Flow rates are calculated using the Pharmacy SPU printout provided with each PN when delivered from Pharmacy - Divide the total volume for the baby in the aqueous bag and lipid container by 24 or 48 as appropriate to give hourly rates. - Check against flow rate on the labels Recording Flow Rate Changes All changes must be recorded on a separate record sheet and signed by 2 nurses. (Appendix 10) 4.3 Prescribing Bespoke Neonatal PN Regimens These have been designed for use only when none of the manufactured bags can be tailored to meet the needs of an individual infant. These should only be used if absolutely necessary and only following discussion with the Attending NICU Consultant, Neonatal Dietitian and/or Neonatal PN Pharmacist to ensure selection of the most appropriate regimen on which to base a prescription. Neonatal Bespoke PN Prescription Charts are printed on lilac paper (Appendix 6). The guide to prescribing Bespoke PN should be used (Appendix 6A). The need for Bespoke prescribing should be reviewed on a daily basis to ensure the infant would not be more appropriately managed using one of the Tailored Neonatal PN Regimens. 8

9 Nottingham Neonatal Service Clinical Guideline D6 Bespoke Neonatal PN Regimens see prescribing guide (Appendix 6A): The Bespoke Regimens suggested are only for use when the needs of the infant cannot be achieved with modifications to the standard bag. They are a guide only, and have been designed to allow maximum flexibility. However, prescribers must be aware that there is greater opportunity for error when individually prescribing. Stability data is available over a wide nutritional range. Protein is the defined nutrient around which other nutrients are modified and, on the prescription, the standard for each is in bold with minimum and maximum given in brackets (Table 2). The advice and the signature of the Attending Neonatal Consultant is required for the prescription of Bespoke Regimens and, in addition, advice should be sought from the Neonatal Dietitian or Neonatal PN Pharmacist where possible. Every nutrient needs individual consideration as figures given in Table 2 are only a guide. Bespoke T Term suggested as a basis for infants born 34w providing 2.5g protein/kg/day to allow reduction of any component or changes outside stability matrix. May be prescribed at 90ml/kg/day when fluid restriction is required Bespoke P - Preterm suggested as a basis for infants born <34w providing 3.5g protein/kg/day to allow reduction of any component or changes outside stability matrix. May be prescribed at 100ml/kg/day when fluid restriction is required Bespoke S Special suggested as a basis for preterm infants requiring additional nutrition providing 0.64g N (= 4g protein/kg/day) and 17g glucose/kg/day. May be prescribed at ~100ml/kg/day when fluid restriction is required Bespoke R Renal only at specific request of the Paediatric Renal Consultant or Dietitian Fluid restriction is usually required in the management of acute renal failure (ARF) which will reduce protein when standard Preterm (P) or Term (T) PN is prescribed. Most infants with ARF can be managed by tailoring standard PN or if fluid, potassium or phosphate need further restricting then Bespoke P or T can be used as a basis. Bespoke R is intended for very occasional use in infants with ongoing renal failure and can only be prescribed from scratch by a consultant, with neonatal or paediatric renal dietitian involvement. There is no obvious facility to select this on the Bespoke prescription. Table 2 Composition of Bespoke Regimens - standard amounts with (min & max) Regimen (min - max) T - Term P - Preterm S - Special R - Renal Nitrogen g/kg/day Protein g/kg/day Glucose g/kg/day 15 (13 18) 15 (13-18) 17 (15-18) 17 (15 18) Fat* see below g/kg/day 3 (0.5-4) 3 (0.5-4) 3 (0.5-4) 3 (0.5 4) Sodium** mmol/kg/day 3 (1.5-15) 3.5 (3.5-15) 3.5 (3.5-15) 3 (1.5 15) Potassium mmol/kg/day 2.5 (0-5) 2.5 (0-5) 2.5 (0-5) 1 (0 5) Calcium mmol/kg/day 1.0 (0-2) 2.0 (0-2.5) 2.0 (0-2.5) 1.0 (0-2) Magnesium mmol/kg/day 0.2 (0-0.2) 0.2 (0-0.2) 0.2 (0-0.2) 0.2 (0 0.2) Phosphate mmol/kg/day 1.0 (0-2) 2.0 (0 2.5) 2.0 (0 2.5) 1.0 (0 2) Trace Elements ml/kg/day Fat Soluble Vits ml/kg/day 4 (max 10ml/d) 4 (max 10ml/d) 4 (max 10ml/d) 4 (max 10ml/d) Water Soluble Vits ml/kg/day Target Volume ml/kg/day 120 (90-120) 120 ( ) 100 ( ) For minimum request no added water *Prescribe fat at 2g/kg/day for first 48 hours of PN for preterm infants ** Na can be nil in all regimens but at the expense of phosphate rarely necessary to reduce below standard Acetate greater than provided by Aminoven can be prescribed in Bespoke PN by circling Yes on the prescription (or No for no additional acetate). See Section 5.4 for details 9

10 Nottingham Neonatal Service Clinical Guideline D6 4.4 Prescribing Basic Stock PN A small stock of Basic Stock Preterm and Term PN is kept on the neonatal unit for use when an individually prescribed regimen is not available. These contain standard nutrients as in Table 1 but, in order to extend shelf life, do not contain vitamins or trace minerals, so should only be used short term. A Tailored PN Regimen should be ordered as soon as possible. The indication for the use of Basic Stock PN must ALWAYS be clearly documented in the infant s medical case records, for example: an error was made and PN was not prescribed from Pharmacy SPU or the PN supplied from Pharmacy SPU for the infant is no longer appropriate the baby is > 48 hours of age, requires PN according to guidance in this guideline and has been admitted from another neonatal unit at a time of day when Tailored PN from Pharmacy SPU will not be made available for at least 8 hours the bag of PN supplied from Pharmacy SPU for the infant is damaged Care must be taken to ensure that the components of Basic Stock PN meet the needs of the infant. Basic Stock Preterm and Basic Stock Term PN are prescribed using the prescription sheet in the bag (Appendix 7) and a replacement bag ordered by completing and returning the re-order sheet (Appendix 8) to SPU. In order to ensure appropriate balance of aqueous and lipid the full amount for 24 hours must be prescribed and flow rates calculated. Nursing staff will use these flow rates to calculate lower infusion volumes in babes receiving both PN and milk. The total volume will be 115ml/kg if 3g/kg/day of lipid is prescribed (or 110ml/g if 2g/kg/day of lipid is prescribed) due to the omission of vitamins and trace minerals These bags should only be used on agreement with Attending NICU Consultant. Absolutely no modifications to Basic Stock PN can be made. Any additional electrolytes and minerals must be given as extra infusions according to neonatal guidelines. Neonatal PN is intended for use in patients cared for on the NICU, though can be continued if transferred to paediatrics. To identify the 3 regimens stored on NICU, coloured stickers and prescriptions are used and the regimens are clearly marked: Starter Preterm PN: white Basic Stock Preterm PN: blue Basic Stock Term PN: red sticker/pink prescription. 4.5 Enteral Nutrition Minimal enteral feeding Enteral nutrition should always be used where possible. Volumes of milk as small as 0.5ml every 4 hours have been shown to decrease the risk of PN related cholestasis and decrease the time taken to establish full enteral nutrition [21]. It is recommended that 1ml/kg of maternal colostrum/early expressed breast milk is given every 2 hours via gastric tube as soon after birth as possible. This should be started as soon as clinically indicated and continued until transition to enteral feeding is commenced. Failure to progress with enteral feeds should result in return to minimal feeding, rather than nil by mouth whenever possible. More detailed guidance is available in Guideline D Transition to enteral feeding The transition to enteral feeding should be made according to Nottingham Neonatal Service Guideline D3 and clinical decisions made on daily consultant review. A baby receiving 120 ml/kg/day PN should ideally receive 30ml/kg/day milk before the decrease in PN commences, sometimes up to 50ml/kg where additional nutrition is required. Increases in enteral feeds beyond this should be matched by a proportional decrease of parenteral nutrition, ensuring a good nutritional intake within an agreed fluid allowance. Once 150ml/kg/day is achieved enterally PN should not be required as BMF will be added to EBM according to guideline D7A. 10

11 Nottingham Neonatal Service Clinical Guideline D6 4.6 Drugs and PN Drugs must never be added to PN Where insulin is required to ensure glucose tolerance (Section 5.3), insulin infusion into the line used for PN preferred so that continued insulin infusion does not occur if the PN infusion rate drops as may occur in line blockage. Ideally, other drugs should not be infused via the same line as PN. However, some drugs may practically need to be infused through the same line as PN. As there are some important incompatibilities, staff should ALWAYS refer to the Neonatal Drug Monographs available in the Drug Information folder on the Neonatal Intensive Care Units, on the NUH Intranet and NUH Guidelines app. Advise should be sought from neonatal pharmacist where necessary. 4.7 Monitoring requirements due to receiving PN The monitoring suggested below is purely for monitoring PN and other monitoring according to clinical condition of the baby may be required. Daily: Mon/Wed/Fri: Weekly: Monthly: Urea & electrolytes (until tolerating full PN), blood glucose, FBC, U & E (once tolerating full PN) LFTs, Ca, PO 4, Mg After 4 weeks Selenium (Se), Copper (Cu), Zinc (Zn) and Manganese (Mn) More frequent monitoring of calcium and phosphate may be required in unstable infants. Triglycerides should be monitored if using more than 3g fat/kg/day to check tolerance or following visually lipaemic sample until seen to be <2.8mmol/l (see Section 3.4). 5 Complications/Problems 5.1 Infection Neonatal PN is usually delivered through a percutaneous long line or surgically placed central line. These should only accessed when absolutely necessary and full aseptic precautions should always be used for siting and handling both. Dressings must be clean, fully adherent and checked at least daily. In the presence of proven line infection, the long line should be removed and not usually re-sited for 48 hours whilst antibiotics are given. Occasionally, if line placement is difficult, the line may be kept in situ and antibiotics given via it. If sepsis continues, the line should be removed. The Attending Consultant Neonatologist should decide whether the line is to be removed. Nutrition is vital during septic episodes. PN should be continued in most cases of suspected infection. Recent data suggests that both energy and protein requirements increase, particularly in ELBW infants. Where possible, efforts should be made to try and maintain appropriate nutrition with the aim of minimising nutritional deficits and maintaining growth [22, 23]. There isn t sufficient evidence to support routine increase of energy intake during sepsis. As nutrition is vital, in most infants for whom infection is suspected, full nutrition should be continued when possible. 5.2 Cholestasis The risk of cholestasis will increase with degree of prematurity, sepsis, duration of PN and also the absence of enteral feeding. If PN is maintained in the presence of cholestasis, this may progress to cirrhosis. This risk must be considered in each individual and balanced against the risks of malnutrition. A major factor in preventing cholestasis is use of the gut. Enteral feeding is known to decrease the likelihood of cholestatic jaundice and should be employed whenever possible. An alternative lipid source (SMOF lipid a blend of Soya, Medium chain triglycerides, Olive and Fish oils) is available and may reduce cholestatic jaundice. This may be considered in infants likely to require long term PN or who have high circulating concentrations of conjugated bilirubin. This should be discussed with the Attending Consultant Neonatologist and Neonatal Dietitian or Neonatal PN Pharmacist as clear evidence of benefit in preterm infants is not yet available [24]. 11

12 Nottingham Neonatal Service Clinical Guideline D6 5.3 Hyperglycaemia Gradual introduction of glucose up to 15g per kg (equivalent 10.4 mg/kg/minute) occurs as nutrition is introduced according to a gradual increase in fluids. Smaller, more premature, infants are likely to have the greatest problems tolerating glucose and they are also the infants who often need more rapid increase in fluids. Close monitoring of blood glucose, along with calculation of the actual amount of glucose being infused, is essential in decision making to prevent rapid increase of PN and poor tolerance of glucose. PN can be supplemented with 5% dextrose to achieve larger fluid volumes in these infants. Reducing glucose to a level of tolerance by reducing PN prescription will compromise nutrition as all nutrients in the aqueous bag will be reduced. Bespoke prescribing with reduced glucose is possible but should only ever be short term and even so, if tolerance doesn t improve, insulin should be considered. Although there is evidence of successful use of insulin to control hyperglycaemia in the preterm infant [25, 26], studies do not support prophylactic use in the absence of hyperglycaemia [27]. Insulin should be considered at a blood glucose >10 on repeated measurements AND +++ (or more) of glycosuria on bedside testing. Blood glucose should be confirmed either by the electrode method of glucose measurement where this is available (i.e. using the blood gas machine) or by the laboratory. Other bedside methods of blood glucose measurement are inaccurate in newborn infants and should not be used. Use of insulin should be discussed with the Attending Consultant Neonatologist and increased frequency of blood glucose measurements agreed. See Drug Monographs for insulin sliding scale. 5.4 Acidosis (causes other than sepsis) PN is a factor in metabolic acidosis in preterm infants. Chloride load is probably the major factor so alternative (non-chloride) salts are used where possible. Acetate, which can be used as a substitute for chloride, is metabolised to base so may be beneficial both in its own right and as a means of reducing chloride. Acetate is also present in Aminoven (the amino acid source). The Tailored Preterm Regimen has the standard 3.5mmol sodium/kg provided as sodium glycerophosphate and standard 2.5mmol potassium/kg as potassium acetate. Additional sodium or potassium is added as chloride. The amount of acetate provided per kg is: Tailored Preterm Starter Regimen - 2.2mmol Tailored Preterm Standard Regimen - 4.7mmol Tailored Term Regimen - 1.6mmol Acetate up to a maximum of 6mmol/kg/day can be requested by prescribing a Bespoke regimen. Bespoke Regimens have the acetate provided by Aminoven and the option of additional acetate is available by circling Yes in the Acetate box. In that case, sodium acetate will be used for any extra sodium not added as Na glycerophosphate, and potassium acetate used as the potassium source. Acetate will only be added to a maximum of 6mmol/kg/day due to risk of hypercarbia [16]. As acetate is not usually required by infants born at term, acetate above that provided by Aminoven is not added to Tailored Term Regimens. When Bespoke prescribing for infants born >34weeks, the prescription chart directs prescribing so no additional acetate is prescribed in Bespoke T regimen. 12

13 Nottingham Neonatal Service Clinical Guideline D6 References 1. AAP, Nutritional needs of the preterm infant, in Pediatric Nutrition Handbook 5th Ed, R.E. Kleinman, Editor. 2003, AAP. p Embleton, N.E., N. Pang, and R.J. Cooke, Postnatal malnutrition and growth retardation: an inevitable consequence of current recommendations in preterm infants? Pediatrics, (2): p Martin, C.R., et al., Nutritional practices and growth velocity in the first month of life in extremely premature infants. Pediatrics, (2): p Ehrenkranz, R.A., et al., Growth in the neonatal intensive care unit influences neurodevelopmental and growth outcomes of extremely low birth weight infants. Pediatrics, (4): p Dinerstein, A., et al., Early and aggressive nutritional strategy (parenteral and enteral) decreases postnatal growth failure in very low birth weight infants. Journal of Perinatology, (7): p Denne, S.C. and B.B. Poindexter, Evidence supporting early nutritional support with parenteral amino acid infusion. Seminars in Perinatology, (2): p Thureen, P. and W. Heird, Protein and energy requirements of the preterm/low birthweight infant. Pediatr Res, (5_Part_2): p. 95R Nose, O., et al., Effect of the energy source on changes in energy expenditure, respiratory quotient, and nitrogen balance during total parenteral nutrition in children. Pediatric Research, (6): p Rayyan, M., et al., Short-term use of parenteral nutrition with a lipid emulsion containing a mixture of soybean oil, olive oil, medium-chain triglycerides, and fish oil: a randomized double-blind study in preterm infants. Journal of Parenteral & Enteral Nutrition, (1 Suppl): p. 81S-94S. 10. Uthaya, S., et al., Nutritional Evaluation and Optimisation in Neonates: a randomized, double-blind controlled trial of amino acid regimen and intravenous lipid composition in preterm parenteral nutrition. The American Journal of Clinical Nutrition, (6): p Brans, Y., et al., Tolerance of fat emulsions in very-low-birth-weight neonates. American Journal of Diseases of Children, (2): p Hilliard, J.L., et al., Plasma lipid levels in preterm neonates receiving parenteral fat emulsions. Archives of Disease in Childhood., (1): p Koletzko, B., et al., Guidelines on Paediatric Parenteral Nutrition: ESPGHAN, ESPEN, ESPR. Journal of Pediatric Gastroenterology & Nutrition, (Suppl 2): p. S1 - S Drenckpohl, D., et al., Randomised trial of VLBW infants receiving higher infusions of intravenous fat emulsions during the first week of life. Pediatrics, (4): p Lapillonne, A., Enteral and parenteral lipid requirements of preterm infants, in Nutritional care of preterm infants: scientific basis and practical guidelines, B. Koletzko, B. Poindexter, and R. Uauy, Editors. 2014, Karger. p Peters, O., et al., Randomised controlled trial of acetate in preterm neonates receiving parenteral nutrition. Archives of Disease in Childhood Fetal & Neonatal Edition., (1): p. F Mimouni, F.B., D. Mandel, and R. Lubetzky, Calcium, phosphorus, magnesium and vitamin D requirements of the preterm infant, in Nutritional Care of Preterm Infants: Scientific Basis and Practical Guidelines, B. Koletzko, B. Poindexter, and R. Uauy, Editors. 2014, Karger. p Paediatric Formulary Committee, in BNF for Children , BMJ Group, Pharmaceutical Press, and RCPCH Publications: London. 19. Fresenius Kabi, Manganese and liver function - Peditrace Company Data, Hambidge, K., et al., Plasma manganese concentrations in infants and children receiving parenteral nutrition. Journal of Parenteral & Enteral Nutrition, (2): p Tyson, J.E. and K.A. Kennedy, Trophic feedings for parenterally fed infants. Cochrane Database of Systematic Reviews, Torine, I., et al., Effect of late-onset sepsis on energy expenditure in extremely premature infants. Pediatric Research, (5, Part 1): p Mrozek, J., et al., Effect of sepsis syndrome on neonatal protein and energy metabolism. Journal of Perinatology, (2): p Uthaya, S., et al., Nutritional evaluation and optimisation in neonates (NEON) trial of amino acid regimen and intravenous lipid composition in preterm parenteral nutrition: a randomised double-blind controlled trial. Efficacy and Mechanism Evaluation, (2): p Collins, J., et al., A controlled trial of insulin infusion and parenteral nutrition in extremely low birth weight infants with glucose intolerance. The Journal of Pediatrics, (6): p Kanarek, K.S., M.L. Santeiro, and J.I. Malone, Continuous infusion of insulin in hyperglycemic lowbirth weight infants receiving parenteral nutrition with and without lipid emulsion. Journal of Parenteral & Enteral Nutrition, (4): p Beardsall, K., et al., Early insulin therapy in very-low-birth-weight infants. New England Journal of Medicine, (18): p

14 Nottingham Neonatal Service Guideline D6 PN Appendices 1&2 Appendix 1 Summary NICU Parenteral Nutrition (PN) Regimens (for details see Nottingham Neonatal Service Clinical Guideline D6) To optimise nutrition, standardise and ensure safe practice a series of PN regimens has been designed to meet the needs of the majority of infants on the unit. These are available in manufactured standard bags, but most can be Tailored to meet increased electrolyte and bone mineral requirements. There will be occasions when these will not meet the needs of individual infants so Bespoke regimens can be individually manufactured in Pharmacy SPU. Efforts should be made to minimise the volume of other infusions in order to maximise nutritional intake. Starter Preterm Regimen PN is ready for use in 200ml bags in the NICU fridge. It is intended for use from birth in infants <30w or <1.25kg for a maximum of 48 hours. It is similar to the aqueous component of full Preterm Regimen but has no sodium, vitamins or trace minerals and less potassium, calcium and phosphate. It should usually be prescribed according to individual fluid prescription up to 80ml/kg/day providing 8.3mg/kg/min glucose. Fluid requirements above this are usually prescribed as 5% dextrose. However, up to 100ml/kg/day (10.4mg glucose/kg/min) may be prescribed providing glucose tolerance is assured by regular measurement of blood glucose. Starter Preterm PN cannot be modified and is designed for central administration only. Standard Tailored Preterm Regimen PN will ideally follow Starter Preterm PN and be commenced between hours of age to provide optimum nutrition and a lipid infusion containing vitamins. The exact timing will depend on the time of birth and Pharmacy SPU availability. Attention should be paid to ensuring that Tailored Preterm Regimen PN is prescribed for provision within this time window. Tailored Preterm PN provides full nutrition as ~100ml/kg of the aqueous bag and ~20ml/kg of lipid (fat). Lipid should be prescribed at 2g/kg/d (12.5ml/kg) for 48 hours, and thereafter at 3g/kg/d (17.5ml/kg). Tailored Preterm Regimen is designed for central administration only. Standard Tailored Term/Near-Term Regimen (known as Term Regimen) - is designed for infants born >34 weeks and is not routinely used for preterm infants still requiring PN at term corrected age who may still have increased requirements. Nutrition provided will increase as fluid allowance increases to a maximum of 120ml/kg/day. Tailored Term Regimen is designed for central administration only. Basic Stock PN a small supply of Preterm and Term PN will be available on the NICU for use in situations where Tailored PN Regimens are not available, such as for infants admitted at >24 hours of age, Pharmacy SPU is closed, altered clinical condition, etc. A prescribing guide and re-order form are available with each bag and MUST be completed. Basic Stock Regimens are designed for central administration and for use in babies on NICU only. Bespoke PN Regimens These should only be used if absolutely necessary and only following discussion with the Attending NICU Consultant, Neonatal Dietitian and/or Neonatal PN Pharmacist. Bespoke T Term - suggested as a basis for infants born 34w providing 2.5g protein/kg/day to allow reduction of any component or changes outside stability matrix. May be prescribed at 90ml/kg/day when fluid restriction is required Bespoke P Preterm - suggested as a basis for infants born <34w providing 3.5g protein/kg/day to allow reduction of any component or changes outside stability matrix. May be prescribed at 100ml/kg/day when fluid restriction is required Bespoke S Special suggested as a basis for preterm infants requiring additional nutrition providing 0.64g N (= 4g protein/kg/day) and 17g glucose/kg/day. May be prescribed at ~100ml/kg/day when fluid restriction is required. Please discuss with dietitian prior to prescribing Bespoke R Renal only at specific request of the Paediatric Renal Consultant or Dietitian Fluid restriction is usually required in the management of acute renal failure (ARF), which will reduce protein when standard Preterm (P) or Term (T) PN is prescribed. Most infants with ARF can be managed by tailoring standard PN or if fluid, potassium or phosphate need further restricting then Bespoke P or T can be used as a basis. Additional energy may be required to allow optimum use of protein. Bespoke R in intended for very occasional use in infants with established chronic renal failure and can only be prescribed from scratch by a consultant, with neonatal or paediatric renal dietitian involvement, so there is no obvious facility to select this on the Bespoke prescription.

15 Appendix 2 Nottingham Neonatal Service Guideline D6 PN Appendices 1&2 Nutritional Composition of PN Regimens When Prescribed at Regimen Standards Preterm Starter /kg/day Volume ml Protein g Glucose* g mg/kg/min Fat g Energy kcal Na mmol K mmol Ca mmol Mg mmol P mmol *minimum expected glucose requirement 4-6mg/kg/min ( g/kg/day) Preterm Standard (with either 2 / 3g fat/kg/day) /kg/day Volume ml Protein g Glucose g mg/kg/min Fat g 0.7 / / / / / / / / / 3.0 Energy kcal 31 / / / / / / / / / 104 Na mmol K mmol Ca mmol Mg mmol P mmol Term Standard (with 3g fat/kg/day) /kg/day Volume ml Protein g Glucose g mg/kg/min Fat g Energy kcal Na mmol K mmol Ca mmol Mg mmol P mmol A detailed nutritional profile of the Bespoke regimens is not given here as the basic composition given in table 2 of guideline D6, is only intended as a guide and basis for individual prescribing. It is, therefore, essential to involve the neonatal consultant, neonatal dietitian and neonatal PN pharmacist prior to prescribing to ensure that optimum individual requirements are achieved. An algorithm to guide bespoke prescribing is appended to the PN guideline (appendix 6a). A laminated copy is available on the unit with the prescription. 2