🗊Презентация Parenteral Nutrition in Neonates

بسم الله الرحمن الرحيم

Parenteral Nutrition in Neonates Prepared By Neveen Hassan Abdel Aal Clinical Pharmacist at NICU Assuit University Children’s Hospital

What are we going to discuss? Parenteral Nutrition: Definition & Goals. Types of PN Admixtures. Routes of Administration of PN. Nutritional Components of PN Formula. Macronutrients : Daily requirements, Regimen, Special consideration. Micronutrients : Daily requirements, Regimen, Special consideration. Complications of PN. Monitoring of PN. Weaning of PN.

Parenteral Nutrition PN is the administration of intravenous nutrition in patients with a Non- functioning or Inaccessible GIT in which it is anticipated that the patient will be unable to be fed enteral for at least 3 days in Neonates.

Parenteral Nutrition Goals (1) Weight maintenance or promoting growth. (2) Preservation of lean body mass& visceral proteins. (3) Correct or prevent nutritional deficiencies. (4) Avoidance of vitamins & trace elements abnormalities. (5) Avoidance of fluid& electrolyte abnormalities.

Types of PN Admixtures 2 in 1

Routes of Administration of PN

Central Access

Central Access

Criteria for Peripheral Administration Osmolarity must not exceed 900 mOsm/L. Final dextrose concentration should be ˂10% (Don’t exceed 12.5%) Final AA concentration should be 2.5%–4% Ca2+ concentration should be ˂ 5 mEq/L K+ concentration should be ˂40–60 mEq/L

Nutritional Components of PN Formulation PN should provide a balanced nutritional intake of 1) Macronutrients including (amino acids, dextrose , Fat emulsions) They are important sources of structural & energy yielding substrates. 2)Electrolytes & micronutrients (including vitamins & trace elements) Are required to support essential biochemical reactions, metabolic activities , maintain physiologic serum concentrations.

Estimating the Osmolarity of Parenteral nutrients

Calculating the Osmolarity of a Parenteral Nutrition Solution Multiply the grams of dextrose per liter by 5. Multiply the grams of protein per liter by 10. Multiply the (mEq per L sodium + potassium + calcium + magnesium) X 2 [glucose (g/L) × 5] +[amino acids (g/L)×10]+ [cations (mEq/L)× 2]

Developing a Regimen for PN Administration Through Central Line

I. Evaluation of patient case PN components should be adjusted individually to each patient according to: Clinical status Nutritional status Nutritional requirements Underlying disease state Level of metabolic stress Organ functions

I. Evaluation of patient case First of all Review: Patient Age, weight ( Kg). Make sure that patient is good candidate for PN. Investigate patient lab values : Electrolytes: serum level of Na+, K+, Ca2+, etc. Evaluate Kidney function through Cr level & BUN. Evaluate Liver function through ALT & AST level. Lipid profile Serum Albumin, Pre-albumin , Transferrin C- reactive protein & Complete Blood Count (CBC)

Evaluation of patient case continue 4. Assessment of degree of hydration. Signs of dehydration: Reduced urine output BUN : Cr ˃ 10 : 1 Decreased skin turgor Dry mucous membrane

II. Start Calculating Components of PN Formula Steps of Calculation Fluid need/tolerated (Subtract drugs, Blood, O.R.S, milk from TFR) Patient's energy needs (Kcal/day) - Protein need/day - Fat emulsion need/tolerated - Dextrose need/concentration - Electrolytes /trace elements /vitamins need - Osmolality - Route - TPN soln: 2 in 1, 3 in 1

1.Determine Fluid Requirements

Daily maintenance of fluids intake on body weight basis

The Neonatal adaptation processes after birth may be divided into three major phases:

Variations in Fluid Requirements Do not use PN for fluid replacement but for maintenance fluid only. Patients with the following conditions may have increased fluid requirements: fever, burn, diabetes insipidus , diarrhea, ileostomy or biliary drainage, and hyperbilirubinemia. Patients with the following conditions may have decreased fluid requirements: hypothermia, syndrome of inappropriate antidiuretic hormone, oliguric renal failure, or patent ductus arteriosus, other Kidney or Cardiac dysfunction.

Suggested initial adjustment in specific situations Fever…..+12% for each degree >37 c. High humidity…..0.7 × maintenance. Radiant heat…..1.5 × maintenance. Photo Therapy… 10% × number of photo units× maintenance Congestive HF…..0.5 ×maintenance. Brain injury…….0.5-0.7 × maintenance. Renal failure………0.3 ×maintenance + urine output. Mechanical ventilation….(using humidifiers)0.7×maintenance

Adjustment of Fluid Requirements in case of Kidney Dysfunction TFR= I.W.L + U.O.P Insensible water loss (IWL): Used if urine output <1 ml/kg/hour

2. Determine Caloric Requirements

Parenteral energy needs may be roughly estimated using the following ranges

Factors affecting variations in caloric requirements Further aspects need to be taken into account according to clinical parameters: Weight gain in regard to the target growth and required catch-up growth. Recommended intake of the different macronutrients Tolerance to PN administration (i.e. hyperglycaemia, hypertriglyceridaemia, liver enzyme abnormalities, cholestasis). Nutritional status, underlying diseases, energy intake, energy losses, age.

Variations in Caloric Requirements Patient require increased caloric needs in case of fever, inflammation, sepsis, burn, cardiac or pulmonary disease, major complicated surgery, and patients requiring “catch up” growth. Patients require decreased caloric needs in case of sedation, pentobarbital coma, mechanical ventilation, or paralysis.

Factors that increase caloric requirements

The Caloric balance of PN Formula Caloric needs are met by a proper balance of carbohydrates, proteins, and fats, A balanced PN formula of total daily calories should include: According to ASPEN Recommendations 1) 10-20 % amino acid. 2) 50-60 % dextrose. 3) 20-30 % Fat emulsion. According to ESPEN Recommendations energy needs can be calculated based on non protein calories as protein needs are calculated only for new tissue deposition, as well as for tissue renewal and not as an energy source. Glucose should cover 60–75% of non-protein calories. Lipid should provide 25–40% of non-protein calories.

3.Determine Protein Requirements Proteins are the major structural and functional components of all cells in the body. Amino acid supply should start on the first postnatal day.

Protein requirements of neonates and children depend on age and weight

Regimen of Protein Administration Start with 1.5 gm/kg/d and then increase by 1 gm/kg/d to maximum of 3.5 - 4 gm/kg/d. Advance or wean of protein dose , depend on the serum BUN level and protein goals.

Protein requirements Variations Increased amount of amino acids are required in case of patients with short bowel syndrome, Stress (trauma, infection, Burn, surgery), wound healing. Patients with kidney dysfunction may need a protein restriction . Kidney dysfunction without dialysis, 0.5–1 g/kg/day Kidney failure with intermittent haemodialysis, 1.2–1.5 g/kg/day (1.5–2.5 g/kg/day if continuous renal replacement)

Potential complications and risks of providing IV amino acids 1- Acidosis 2- Elevated BUN 3- Hyper- ammonaemia 4- Cholestasis (with prolonged administration)

Caloric Value of Proteins Calories from protein (4 kcal/g) Inadequate supplementation of energy from carbohydrates and lipids results in protein breakdown for energy instead of growth, Therefore Protein calorie/non protein calorie ratio should be kept in range of 1:8-1:10 Values less than 1:6 are likely to result in hyperaminocidemia & aminoaciduria.

4.Determine Lipid Requirements Providing fat is essential to Achieve adequate caloric intake in TPN Utilize amino acid effectively. Prevent or treat essential fatty acid deficiency

The lipid requirements of neonates and children depending on age

Regimen of Lipid Administration Starting dose of 1 g/kg/day Titrate toward the goal as tolerated by serum triglyceride levels to 3 g/kg/day by day 4. If lipid infusion is increased in increments of 0.5 to 1 g/kg per day, it may be possible to monitor for hypertriglyceridaemia.

Caloric Value of Lipids Calories from Lipid (10 kcal/g) Maximum fat oxidation occurs when intravenous lipid emulsions provide 40% of the non-protein PN calories in newborns . A higher percentage of calories from lipid (up to 50%–60% of the non-protein PN calories ) ,can be provided for a short time in certain cases (e.g., hyperglycaemia, hypercapnia). Do not allow lipids to exceed 60% of total caloric intake.

Precautions For Neonates Restrict the dose of lipids in minimum amounts that will provide only the essential fatty acids following acute episodes of: 1) Thrombocytopenia 2) Sepsis 3) Respiratory distress Lipids when given as a slow infusion over 24 hours are not associated with worsening of respiratory distress. 4) Severe hyperbilirubinemia who are on phototherapy . In this case, lipids may need to be limited to 0.5 - 1.5 g/kg/day.

Potential complications and risks of providing IV Lipids Hyperlipidemia. Potential increased risk or exacerbation of chronic lung disease. Potential exacerbation of Persistent Pulmonary Hypertension (PPHN). Lipid overload syndrome with coagulopathy and liver fail. Cholestasis. (In patients with marked progressive cholestasis associated with PN, unrelated to acute infection, a decrease or even a transient interruption in intravenous lipid supply should be considered.) potentially kernicterus in premature infants.

Monitoring Plasma clearance of infused triglycerides can be assessed by measurement of plasma triglyceride concentrations. Checking serum triglyceride levels should be considered with each increase of 1.0 g/kg per day of intravenous lipids and weekly after the maximum dose is achieved to prevent or provide early identification of these complications. When triglyceride levels become Elevated ( 200 mg/dl or 1.8 mmol/L), consider decreasing the daily dose & if it is severely elevated ( 300 mg/dl or 3 mmol/L), omit lipids until levels return to normal. Serum triglyceride levels in serum should be monitored closely in patients receiving lipid emulsions, particularly in cases with a marked risk for hyperlipidaemia (e.g. patients with high lipid dosage, sepsis, catabolism, extremely low birthweight infants).

5. Determine Carbohydrates Requirements Dextrose is major immediate energy source . Several body tissues depend mainly on dextrose for energy including CNS, RBCS & the renal medulla. Dextrose is the main source of calories in PN, and usually represent most of the osmolality of the solution.

Estimation of carbohydrates requirements Recommended parenteral glucose supply (g/kg/day)

Variations in Carbohydrates Requirements Carbohydrates Requirements need to be adapted according to Age and clinical situation (e.g. malnutrition, acute illness, drug administration, refeeding syndrome in severe malnutrition) oral and/or enteral energy intake the required weight gain for normal or catch up growth. Glucose intake should be adapted in case of simultaneous administration of drugs known to impair glucose metabolism such as steroids, somatostatin analogs, tacrolimus.

Regimen of Carbohydrate Administration For neonates: Begin with GIR 4-8 mg/kg/min in preterm 4-6 mg/kg/min in full term 4-6 mg/kg/minute for those weighing ˂ 500 g In critically ill children limit GIR to 5 mg/kg/minute (7.2 g/kg /day). Advance with daily increment of 1-2 mg/kg/min to a goal of 10-12 mg/kg/minute as tolerated.

Caloric Value of Dextrose Dextrose yields 3.4 kcal/ g Peripheral line: maximum dextrose concentration 12.5%. Central line: maximum concentration 25- 30 %.

Potential complications Hyperglycemia or hypoglycemia. Glycosuria and potential osmotic diuresis. Cholestasis and/or hepatic steatosis (usually from long-term high concentration infusion). increased CO2 production. Monitoring parameters: blood glucose (<150), CO2 (from blood gas).

Managing Hyperglycemia in Neonates If hyperglycemia develops: ↓GIR insulin may improve glucose tolerance . Do not provide glucose at a rate <3mg/kg/min.  

6. Estimate a Daily Maintenance amount of Electrolytes Vitamins & Trace elements

A) Electrolytes

Electrolytes Requirements

Recommended Parenteral electrolyte intake

Phosphate Normal Ranges by Age

B) Trace Elements Standard trace elements contain selenium, chromium, copper , manganese , and zinc. Neonates on long term TPN may develop trace element deficiencies and it is recommended that their levels should be checked. In general we use only short term TPN and hence do not add trace elements.

Trace Elements Requirements

Pediatrace®

C) Vitamins Requirements Similar to trace elements, multivitamins are often standard in PN unless requested otherwise. Vitamins included in PN include: both fat-soluble vitamins (A, D, E, K) and water-soluble vitamins (C, B 1,2,3,6,7,9,12 ).. Dose 1 ml/kg/day if weight less than 10 kg, if weight more than 10 kg 1 vial every day.

Medication Additives in PN Generally, medications should not be added to PN if it can be avoided. Do not add the following to PN: ceftriaxone (precipitates with Ca), phenytoin (can change the pH of PN), medications containing propylene glycol or ethanol as diluents (e.g., furosemide, diazepam, lorazepam , digoxin, phenytoin, etoposide ), iron dextran (trivalent cations destabilize the lipid emulsion in 3-in-1 PN). Incompatible drugs should be administered through a separate intravenous catheter or a separate lumen of a central venous catheter, if possible. Only regular insulin is compatible with PN.

PN Complications Short term Complications 1- Catheter-related infections 2- Catheter insertion complications 3-Peripheral Thrombophlebitis 4-Gut atrophy 5- Fluid or, Acid- base imbalance 6- Hyperglycemia 5-Overfeeding can cause hepatic steatosis , hypercapnia hyperglycemia, and azotemia. 6-Essential fatty acid deficiency

Short term Complications Continue 7. Refeeding syndrome can occur in acutely or chronically malnourished patients by initiating EN or PN. Characterized by hypophosphatemia, hypokalemia , hypomagnesemia Can cause cardiac dysfunction, respiratory dysfunction, and death Prevention of refeeding syndrome Identify patients at risk Initially, provide less than 50% of caloric requirements; then advance over several days to desired goal. Supplement vitamins as well as potassium, phosphate, magnesium (if needed) before initiating PN . Monitor daily for at least 1 week; and replace electrolytes as needed

Long term Complications 1-Hepatobiliary Disorders (includes steatosis, cholestasis, and gallbladder stones) 2-Osteoporosis & osteomalacia associated with higher protein doses (causes increasedCa2+ excretion) & chronic metabolic acidosis (because of insufficient acetate).

Monitoring PN Administration 1- Infection: Temperature ,WBC , IV access site 2- Peripheral vein thrombophlebitis (if peripheral access) 3- Fluid status: (weight , edema , vital signs, input and output, temperature). 4- Monitor nutritional status Prealbumin Useful in monitoring in patients not critically ill. Goal : increase at least 3-5mg/dl/week until normal Value Normal : 16-40 mg/dl Moderate malnutrition: 11-16mg/dl Severe malnutrition: Less than 11 mg/dl

Monitoring Continue 5-Glycemic control(Hyperglycemia and hypoglycemia.) Goal : 150 mg/dl or less 6- Monitor for electrolyte and acid-base imbalances 7- Monitor Triglyceride level TG more than 400 mg/dl stop lipid 8- Monitor hepatic function. 9- Monitor for patient readiness for oral or EN support.

Monitoring Laboratory measurement

Transition to Oral or Enteral Nutrition When initiating enteral or oral nutrition , monitor for glucose, fluid , and electrolyte abnormalities. Parenteral nutrition, should be continued till the patient is tolerating >50 % of total estimated daily calories & protein requirements via the oral or enteral route , wean PN gradually. PN should be reduced by similar amounts or slightly more than the increase in EN. When should you stop PN? once patient is tolerating at least 75 % of total daily calories & protein requirements via the oral or enteral route.

Recommendations Preterm and Term Infants During the Transition Phase Sodium, chloride and potassium should be supplemented in the first 3–6 days after birth, i.e. in phase I (transition) when contraction of extracellular fluid compartment occurs. Na1 supplementation may start after the first 2 days under monitoring of serum electrolytes levels has shown in Table 1. Preterm and Term Infants During the Stabilisation Phase Phase II (stabilisation) when extracellular fluid compartment contraction is completed may vary in duration from about 5–15 days and is completed when birth weight is regained and the kidneys produce more concentrated urine. Expected weight gain is 10–20 g/kg body weight per day (Table 2). Preterm and Term Infants During the Phase of Established Growth Chloride supplementation follows sodium and potassium. Expected weight gain is 10–20 g/kg body weight per day (Table 3).

Electrolytes Function

Trace Elements Function

Special consideration

Medication Additives Continue Heparin: may be added to the TPN solutions in (0.5 - 1 unit/mL of final PN volume) is added to all central & peripheral lines and to running at < 2ml/ hr in order to Maintain catheter patency Decrease the risk of thrombophlebitis, especially with PPN. Enhance lipid particle clearance by acting as cofactor for lipoprotein lipase enzyme. Concerns about Stability& compatibility of IV lipid with heparin added at concentrations ˃1 unit / ml . In Neonates Use of heparin Recommended where small lumen central lines are used. Contraindicated in neonates with evidence of coagulopathy. The final concentration decreased to 0.5 units/mL in small neonates receiving larger TPN volumes in order to avoid approaching therapeutic amounts.

There is no proven benefit of heparin for the prevention of thrombotic occlusion of CVC’s under regular use in children. Therefore its routine use is not recommended Routine use of heparin has not been shown to be useful in prevention of complications related to peripherally placed percutaneous CVCs in neonates. Heparin does not improve utilisation of intravenous lipids and should not be given with lipid infusion on a routine basis, unless indicated for other reasons. J Pediatr Gastroenterol Nutr, Vol. 41, Suppl. 2, November 2005

Medication Additives Continue Carnitine Should be added if a patient continues to require PN after 10 days and where PN constitutes more than 50% of a patient’s nutrition: Generally recommended to add within the first week of life , to Premature infants of < 34 weeks gestation receiving PN, Carnitine is essential for optimum oxidation of fatty acids (for energy) in the mitochondria. Dose: 10-20 mg/kg. Decreased levels of carnitine occur during prolonged PN without carnitine supplementation. LOE 1 There is no documented benefit of parenteral carnitine supplementation on lipid tolerance, ketogenesis or weight gain of neonates requiring PN. LOE 1 Carnitine supplementation should be considered on an individual basis in patients receiving PN for more than 4 weeks.

Medication Additives Continue H2 antagonist such as famotidine or ranitidine, may be added to the daily PN when indicated. H2 antagonist may indicated to prevent stress related mucosal damage. This provide continuous acid suppression & reduce nursing time by avoiding intermittent scheduled infusions.

Illustrative case A 5-day-old neonate, with gestational age of 28 weeks and birth weight of 900 g with respiratory distress on a ventilator, on TPN since day one.

Answer Step I: Total fluids 150 mL/kg = 135 mL Step II: Amino acid (10%) 1 g/kg/day = 9 ml Step III: Lipids (20%) 1g/kg/day = 4.5 mL Step IV: Supplementation: (1) Sodium 3 meq/kg/day = 18 ml ( NaCl 0.9 %) (2) Potassium 1 meq/kg/day = 0.45 mL (3) Calcium 2 meq/kg/day = 1.8 meq Calcium gluconate 10% = 4 mL (4) MVI 1 mL/kg/day MVI solution = 0.9 mL Step V: Dextrose Infusion: GIR 4 mg / kg/ min Volume of glucose = TFR – ( AA + lipid + Electrolytes) = 135 – ( 9+ 4.5 + 18 + 0.45 + 4+ 0.9 ) = 98 ml Required concentration of glucose =( 0.9× 4 × 60 × 24 × 100)÷ ( 98 × 1000) = 5.2 %

Example for Calculation of Osmolarity [glucose (g/L) × 5] +[amino acids (g/L)×10]+ [cations (mEq/L)× 2] 100 g of dextrose x 5 = 500 mOsm/L 30 g of protein x 10 = 300 mOsm/L 80 mEq of (sodium + potassium + calcium + magnesium) X 2 = 160 Total osmolarity = 500 + 300 + 160 = 1020 mOsm/L