Tomáš Zaoral1, Michal Hladík1, Jana Zapletalová2 1Pediatric intensive care unit, Department of Pediatrics,Faculty of Medicine, University Hospital Ostrava 2The Department of Medical Biophysics, Faculty of Medicine, University hospital Olomouc 8th International Conference on Pediatric Continuous Renal Replacement Therapy (PCRRT) July 2015, London, UK

Single center prospective crossover study January 2009 – December 2014 Setting Pediatric intensive care unit, Department of Pediatrics, University Hospital Ostrava, Czech republic Objective To compare circuit lifetimes during CVVHD in children with heparin and citrate Approved by the Ethics Committee, parental consent was obtained before recruitment 8th pCRRT Conference,16-18 July 2015, London TZ

Single center prospective crossover study January 2009 – December 2014 All children indicated for CVVHD were eligible to participate Age: 0 – 18years All children were on ventilator and sedated Each child received a maximum of 4 circuits with anticoagulants in the following order: heparin, citrate, heparin, citrate (HACG-heparin, citrate –CACG ) The maximum length of one circuit 72 h Circuit life ended when TMP was ≥250mmHg for≥60 min Circuits failed for other reasons were censored 8th pCRRT Conference,16-18 July 2015, London TZ

Single center prospective crossover study January 2009 – December 2014 Exclusion criteria: liver failure, high risk of bleeding or posttraumatic bleeding, thrombocytopenia (below 50 × 10 9 /L) 8 children excluded: 1x LF, 1x ↓ PLT, 6x bleeding or high risk of bl. 8th pCRRT Conference,16-18 July 2015, London TZ

Single center prospective crossover study January 2009 – December children started Premature termination 8children 3x surgery, 3x CT, 2x hemorrhage 63 children received at least 24h of CVVHD (age 89.24±62.9 months, weight 30.37±20.62 kg) Of the 63 children included, 8 received only 2 circuits (1x HACG and 1x CACG), 55 received all four circuits (2x HACG and 2x CACG) we analyzed a total of 118 pairs of HACG and CACG 8th pCRRT Conference,16-18 July 2015, London TZ

Single center prospective crossover study January 2009 – December 2014 Indication for CVVHD: 37 children (58.7%) with oliguria and >10% fluid overload (pRIFLE ) 21 children (33.3%) with elevated creatinin (pRIFLE) 5 children (7.9%) with poisoning 8th pCRRT Conference,16-18 July 2015, London TZ

METHODS All circuits rinsed with heparin IU/5L NS HACG: bolus of 30 IU, than 10 IU/kg/h iv Target APTT 1,5 – 2 of the normal range CACG: 4% trisodium citrate (136 mmol/L) and CaCl2 (500 mmol/L) Basic setting: citrat 4.0 mmol/L Ca 1,7mmol/L iCa ++ the target range of mmol/L iCa++ in the patient’s blood (1.1 – 1.3 mmol/L) 8th pCRRT Conference,16-18 July 2015, London TZ

METHODS Postfilter iCa++ checked q 1h, 6h and 12h After target was achieved q 12h 8th pCRRT Conference,16-18 July 2015, London TZ

CVVHD Citrate protocol in our UNIT INITIAL SETTING : 8th pCRRT Conference,16-18 July 2015, London TZ WeightCVC Blood flow rate ml/min 4% Citrate flow rate ml/hr CaCl 10% ml/hr Dialysate flow rate ml/hr Hemofilter / m 2 Over 30kg 11-12Fr Arrow AV 1000S/1, kg 8-12Fr Medcomp proVencare AV600S/1, kg 8Fr Medcomp proVencare AV400S/0, kg 6,5 - 8Fr proVencare AV400S/0,75 Ultraflux AV ped./0,2 ≤ 3kg 6,5Fr vas.surg.≥ Ultraflux AV ped./0,2

DIALYSIS SOLUTION 8th pCRRT Conference,16-18 July 2015, London TZ Na mmol/L Cl mmol/L Mg mmol/L K mmol/L Ca mmol/L HCO3 mmol/L Glucose g/L PhOsmolarity mosmol/L Ci-Ca dialysate Fresenius MC CITRATE multiBic Fresenius MC HEPARIN

Characteristic pts enrolled in the study All groupSurvivorsNot survivors P Number of pts6342 (66,7%)21 (33,3%) Gender: M/F 35/28 (55,6% / 44,4%) 22/20 (52,4% / 47,6%) 13/8 (61,9% / 38,1%) 0,473 Age (months) 84.0 (1w – 204)88.46 (4 -204)81.42 (1w - 192) 0,770 Weight (kg)26,5 (2,8-82)26,0 (3,3-82)26,5 (2,8-65)0,625 CVC: VJI/SC/VF 41/14/8 (65%/22%/13%) 29/9/4 (69%/21%/10%) 12/5/4 (57%/24%/19%) 0,528 FO >10% (fluid overload) 39 (61,9%)23 (54,8%)16 (76,2%)0,099 Creatinine (umol/l)259,9(76-570,2)271,4(80,4-611,7)249,3(89,3 -480)0,672 Urea (mmol/l)58,8 (19,3-132)56,4 (19,3-131,6)58,8 (21,8-120,5)0,678 PRISM III19 (13-46)16 (13-26)24 (16-46)< 0,0001 MODS23 (36,5%)5 (11,9%)18 (85,7%)< 0,0001 8th pCRRT Conference,16-18 July 2015, London TZ All values represent the number (%) or the mean (range); CVC–central venous catheter; VJI - internal jugular vein; SC - subclavian vein; VF – femoral vein; FO – fluid overload; %FO = ((CRRT initiation weight – ICU admission weight) / ICU admission weight) x 100; PRISM III – pediatric risk of mortality; MODS- multiorgan dysfunction syndrome

DIAGNOSIS 8th pCRRT Conference,16-18 July 2015, London TZ

Total duration of CVVHD (hrs) 9381 Duration of CVVHD (hrs) 4219 (HACG) 5162(CACG) One circuit duration (hrs) 36(18-56) * HACG 41(22-72) * CACG BFR(ml/kg/min) 90 (40-180) Dialysate ml/kg/hr 60,34 (22,2-121,4) Heparin dose (IU/kg/hr) 15 (9,6 - 23,3) 8th pCRRT Conference,16-18 July 2015, London TZ Data are presented as median (min – max) CACG – citrate anticoagulation, HACG - heparin anticoagulation, BFR – blood flow rate, CVVHD – continuous venovenous hemodialysis, NSS –not statistically significant CitrateHeparin P APTT sec 50,3(40,3 - 74,9) 65,4(21,3- 81,7) < 0,0001 Na ( mmol/l) 140( )142( ) < 0,0001 iCa ( mmol/l) 1,13(0,87- 1,31) 1,12(0,99- 1,24) NSS pH 7,41(7,38- 7,48) 7,40(7,37- 7,44) < 0,0001 HCO3 ( mmol/l) 25,20(22,9- 28,7) 24,45(23,1- 26,2) < 0,0001 BE (mmol/l) 0,8(-1,2 - (+)5,5) 0,20(-0,9- (+)1,9) < 0,0001 p  0,0001 Parameters for CVVHD Circuit parameters 6h after initiation CVVHD

Indication Number (%) total=113 Restoration of diuresis38 (33.6) Alarms12 (10.6) Clotting: TMP ≥250 mmHg 54 (47.8) CVC2 (1.76) Death1 (0.88) CT scan/Surgery6 ( 5.3) CACG (%) total=59 HACG (%) total=59 HypoCa: < 0.9 mmol/L4 (6.77)0 (0) HyperCa: > 1.25 mmol/L2 (3.4)0 (0) HypoNa: Na < 130 mmol/L0 (0) HyperNa: Na > 145 mmol/L4 (6.77)1 (1.7%) HypoMg: Mg < 0.70 mmol/L0 (0) pH < 7.36 or BE< - 31 (0.88)0 (0) pH >7.46 or BE> +34 (6.77)0 (0) Reasons for terminating circuitsMetabolic and electrolytes imbalances q.6 h 118 circuits were evaluated, 5 circuits achieved the maximum 72-h duration; 113 circuits ended before 72 h; CVVHD – continuous venovenous hemodialysis; TMP –transmembrane pressure; CVC–central venous catheter; CT-computed tomography 8th pCRRT Conference,16-18 July 2015, London TZ

RESULTS The total mean circuit lifetime 39.75±10.73 Median lifetime for HACG (36.0 h, CI: 35.4 – 36.6) was shorter than for CACG (41.0 h, CI: 37.6 – 44.4  p < ) Total mortality was 33.33%, ≤ 5KG was 75% Dialysis dose was not SS higher in the citrate group (60.34 vs mL/kg/h  p= 1.28) 8th pCRRT Conference,16-18 July 2015, London TZ

Conclusion Citrate lifetimes were shorter for heparin than for citrate Circuit lifetime was significantly correlated to pt age, weight and blood flow rate Mortality was similar to the other studies Mortality was significantly correlated to MODS, PRISM III but not to FO over 10% Metabolic, electrolyte imbalances was readily resolved Citrate was feasible and safe even for infants and newborns 8th pCRRT Conference,16-18 July 2015, London TZ