When fluids go wrong: CRRT in fluid overload Michael Zappitelli MD, MSc

Objectives Early evidence of fluid overload importance in CRRT Fluid overload in non-CRRT patients in the PICU Definition considerations Management considerations

ppCRRT registry: Higher FO, worse outcome Pre-ppCRRT: Goldstein and colleagues: % Fluid overload = (total L in – total L out)/ weight kg X 100 %FO at CRRT start Independent of Oncology Dx MODS Convective clearance PRISM Inotrope #

FO in the PICU FO occurs early in PICU 15 – 20% threshold

Physicians prescribe a lot of fluid FO - oxygenation Cumulative fluid balance worse in nonsurvivors FO: longer ventilation and worse O2 saturation Similar findings several other studies, e.g.: Sinitsky et al, Ped Crit Care Med, 2015 Bhaskar et al, 2014 Seguin et al, 2013, Cardiac surgery Selewski et al, ECMO

Fluid overload definition FO differs Mortality associations same FO, balance-based definition most experience. Use what you think is most accurate in YOUR PICU

Oxygenation parameters improved Does reducing FO with CRRT help? As FO decreased, Oxygenation parameters improved

Should we be starting CRRT “earlier”? Non-survivors started later

Is a trial feasible? What trial? Timing? Based on what criteria? Renal function? Fluid overload? Use of other FO corrective measures? Biomarkers? What markers should we use to guide treatment effectiveness? FO definition Oxygenation Non-renal outcomes Should we be doing a diuretic trial? Goldstein et al: NCT01416298 Using NGAL and FO to guide CRRT initiation and discontinuation

What to do? 12 year old girl with sepsis, on pressors, post initial resuscitation, develops tripling of SCr, positive fluid balance. Begins with awareness: “fluid is a drug” (Goldstein) Explicit effort to measure FO and follow. Speak in terms of that measure and changes in oxygenation (e.g.).

What to do Patient develops XXX% FO and decision to initiate CRRT. Don’t let that “xxx” be more than you want it to be! Quantify the amount of fluid to remove in L: nephro- PICU discuss and agree. Decide on how quickly: CV stability, urgency, bleeding risk (heparin) ~1-2 ml/kg/hour at most; 1 ml/kg/hour to be safe. Avoid > 3-5% BW removal/day if unstable. One way to harm is to do too aggressive UF. nephro-PICU discuss and agree!

What to do You agree that the girl is 5 L positive. She is 40 kg, so 12.5% FO. e.g. You calculate that 1-2 ml/kg/hour ~UF 40- 80/hr, or 1-2L per day. ~5% of BW is about 2L. She is needing significant pressor support, unstable. You choose wisely: -40 ml/hour, ~1L a day

What to do MD – reassess at least twice a day. Nurse: hourly in/out/balance calculation. Consider having an hourly negative limit to call MD. Accept may need to increase pressors, use 25% albumin, to achieve removal. Constant evaluation of removing excess fluids (non-resusc) No need to use diuretics

CRRT stops? Intentional or not Do not allow all of the hard work to be gone. Immediately reassess fluid in to at least achieve neutral balance: guide diuretic therapy. Keep goals in mind: nutrition, lung function. No need to let get very positive.

Summary It makes sense that FO contributes to poor outcome. There is observational data: PICU, PICU-cardiac, ECMO, HSCT which shows this association. Though there are not trials yet, makes sense to: -actively attempt to avoid FO -think about CRRT/RRT for FO earlier, rather than later CRRT fluid removal plan must be: -group effort, planned, continuously revised -SAFE

THANK YOU pCRRT conference organizers Montreal Children’s Hospital AKI research team Collaborators/mentors: Stuart Goldstein, Prasad Devarajan, Chirag Parikh The Kidney Injury During Membrane Oxygenation group