Nutrition during pediatric CRRT Matthew L. Paden, MD Associate Professor of Pediatric Critical Care Director, Pediatric ECMO

Disclosures I’m a pediatric intensivist, talking about renal disease and nutrition….

What do we know about it?

What do we know about it?

Disclosures I’m a pediatric intensivist, talking about renal disease and nutrition…. I don’t know how to optimally feed a critically ill child, whether on CRRT or not. Neither does anyone else.

Recent review of the topic

What do we know? Critical illness and AKI alter normal metabolic pathways Increased gluconeogenesis Decreased glycolysis Increased amino acid oxidation Increased protein breakdown Decreased protein synthesis Impaired lipolysis

Acute and Chronic malnutrition are common Pre-existing malnutrition is under-recognized Castillo et al (doi:10.1186/1471-2369-13-125) 174 pediatric CRRT patients 35% were less than the 3rd percentile for weight 51% mortality vs. 33% mortality if >3rd percentile High risk of protein debt in the first 5 days in the PICU

Total energy needs For critically ill children with AKI “20-30% above basal needs” “35-65 kcal/kg/day” REE via metabolic cart or equations Equations can both under and over estimate REE Kyle, et al. – only getting ~2/3 of daily calories Zappitelli, et al – REE of ~150% was common Daily weights Ben-Hamouda et al – “The patient’s initial weight was 74 kg, and despite feeding to targets validated by repeated indirect calorimetry, the patient lost 18 kg by day 60.”

Carbohydrates – How to measure/monitor it? Glucose monitoring Unclear how often, role of insulin, degree of glucose control

Carbohydrates – How much to prescribe? 20-25% of total energy needs Maximum glucose oxidation rate is ~5 mg/kg/min (Tappy et al, Crit Care Med 1998) Remember to account for replacement fluid and ACD as potential sources of carbohydrate New, et al (doi:10.3945/ajcn.116.139014) – measured in adults this was responsible for ~512 kcal/day No clear recommendations about amount of glucose in replacement or dialysate fluids

Carbohydrates – Outcomes? Risk vs. benefit Further adult studies showed no benefit of strict glycemic control in a medical ICU Higher hypoglycemia rate in children with strict control Effects of additional CO2 generation on mechanical ventilation

Protein – How to measure/monitor it? Total urinary nitrogen Measurement is laborious Urinary urea nitrogen (UUN) 80-90% total nitrogen in non-stressed patients Not valid for AKI, sepsis, liver failure Urea nitrogen appearance (UNA) Normalized protein catabolism rate (nPCR) Fluctuation with metabolically unstable patients Some pediatric data estimating 1-2 g/kg/day Nitrogen balance

Amino Acid in AKI on CRRT Review

Protein - How much to prescribe? Protein turnover is highest in youngest infants Net nitrogen balance is commonly negative in critical illness and AKI ASPEN Recommendations Age (years) Protein (g/kg/day) 0-2 2-3 2-13 1.5-2 13-18 1.5

Protein - How much to prescribe? Not validated for AKI or CRRT Total protein to make up 40-50% of energy provided Additional ~10-20% increase in amino acids due to CRRT losses (Maxvold et al 2000 and Zappitelli et al 2009) ? Role for additional glutamine is unclear Usually this ends up being 2-3 g/kg/day

Protein – Outcomes? RENAL study – (Adults) Dietary protein intake is not associated with mortality Kritmetapak et al – (Adults) Dietary protein intake and albumin associated with mortality (AUC 0.78, OR 4.62) Scheinkestel, et al – (Adults) Positive nitrogen balance, but not protein intake, is associated with mortality Castillo et al – (Kids) Protein energy wasting malnutrition associated with mortality (OR 2.11, CI 1.067-4.173) Often protein is restricted – PPCRRT data Prior to CRRT - ~1 gram/kg/day CRRT – increased to 1.3-2 grams/kg/day

Trace Elements – How to measure/monitor it? Serial monitoring of levels is important Cost? Test 2016 CHOA Charge Copper $45.33 Folate $39.54 Selenium $5.09 Zinc $7.79 Manganese $5.79 Chromium $7.27 Vitamin C $10.98 CRRT/day ~$950

Trace Elements - How much to prescribe? Little published data in adults Citation Increased No Change Decreased Berger et al (PMID 1527716) Zinc Selenium / Copper Thiamine Fernman-Ekholm (doi:10.1080/00365590701514266 Vitamin B12 Folate Klein, et al (JPEN 26:77-93) Kritmetapak, et al (doi:10.1371/journal.pone.0156634) Zinc / Copper Selenium Kamel, et al (doi:10.1177/0884533617716618) Thiamine / Pyridoxine Vitamin C / Folate Ben-Hamouda, et al (doi:10.1016/j.nut.2016.09.012) Copper / Selenium

Trace Elements - How much to prescribe? Little published data for kids Pasko, et al – 5 kids on CRRT – “The daily supplemented trace elements that were removed by CVVHDF never exceeded 20%, and, in most cases, they were less than 5% of the corresponding parenteral trace element supplementation.” Zappitelli, et al – 15 kids on CVVHD – Selenium and folate decreased Copper, chromium, zinc, manganese increased or unchanged

Trace Elements - How much to prescribe? Little published data for kids Pasko, et al – 5 kids on CRRT – “The daily supplemented trace elements that were removed by CVVHDF never exceeded 20%, and, in most cases, they were less than 5% of the corresponding parenteral trace element supplementation.” Start with standard trace element preparation Extra ~100 mcg/day of selenium (adult data) Guided by levels for individual patients Consider additional folate for “long term” CRRT

Vitamin C

Vitamin C

Trace Elements – Outcomes? Success treating known deficiencies that are symptomatic. The outcome of monitoring and treatment of trace elements remains unknown at this point.

Other…. Fat Carnitine 30-40% of energy needs Risk of essential fatty acid deficiency Omega-3, fish oil, etc. – unclear role currently Carnitine Sgambat, et al (doi:10.1111/hdi.12341) – (42 CRRT Kids) Baseline ~1/3rd are carnitine deficient 1 week of CRRT - ~2/3rds are deficient 2 weeks of CRRT - ~90% deficient OR of ~5 for mortality if deficient Ben-Hamouda, et al (doi:10.1016/j.nut.2016.09.012) Cardiomyopathy and skeletal breakdown from severe deficiency

Summary