Pediatric AKI & CRRT: Caring for my Patient & Program? David Selewski, MD Theresa Mottes, RN, NP

Transcription

1 Pediatric AKI & CRRT: Caring for my Patient & Program? David Selewski, MD Theresa Mottes, RN, NP

2 Introduction Pediatric AKI is no longer a mystery issue Growing data on epidemiology and outcome Pediatric CRRT is no longer a novel therapy Experience and literature to support our approach Each patient presents unique challenges Adapting standards to clinical situations Adjusting approach to address complications Each program faces its own issues Technology, support, staffing, acuity, etc.

3 Format for the Session Present a clinical case or question Discuss as a group Review our perspective Case resolution Points illustrated Data/literature review where available Build on clinical examples to discuss QI and program management

4 Pediatric AKI & CRRT Part I HOW DO I CARE FOR MY PATIENT?

5 Case #1 OLIGURIA AND EDEMA

6 Case #1: Case Presentation 14 y/o F s/p stem cell transplant for high-risk ALL Sepsis/hypotension; multiple boluses of IV crystalloid Patient weight initially 38kg, now 44kg Serum creatinine Initial 0.7mg/dL (62µmol/L) Now 2.1mg/dL (186µmol/L) I/O last 24h: 9800ml in/1050ml out 1ml/kg/hr says the resident! BP 90s/50s on pressor support Mechanical ventilation

7 Case #1: Questions Does this patient have acute kidney injury? How do we define AKI in children? Can we prove that a patient has AKI? What s your approach to determining if a patient with AKI needs renal replacement?

8 AKI in Children: KDIGO Criteria Stage Serum creatinine (SCr) criteria Urine output criteria 1 SCr rise by 0.3 mg/dl w/in 48hrs, OR SCr rise by 1.5x to 1.9x reference SCr within 7 days <0.5 ml/kg/hr for > 6 hrs 2 SCr rise 2x to 2.9x reference SCr <0.5 ml/kg/ hr for > 12 h 3 SCr rise 3 X reference SCr OR Increase 4.0 mg/dl OR Renal Replacement Therapy OR egfr in children < 35 ml/min/1.73m2 <0.3 ml/kg/ hr for > 24 h OR anuria for 12 hrs

9 AKI in Children: Epidemiology AWARE Global study of AKI in critically ill children (3mo 25y) 32 Pediatric ICUs >5000 patients enrolled AWAKEN International study of AKI in neonates 24 Neonatal ICUs >2000 infants enrolled

10 AWARE: Prevalence of AKI in PICUs N=4683 AKI: 26.9% Increased risk for ventilator support, RRT, mortality Severe AKI: 11.6%

11 AWAKEN: Prevalence of AKI in NICUs N=2022 AKI: 25.2% Increased risk for mortality; increased length of stay Severe AKI: 15.7%

12 Can We Predict Pediatric AKI? Urinary biomarkers in patients with high AKI risk Markers if damage v. function NGAL Data in adults and children Among 311 children undergoing cardiac surgery (5th quintile) Sensitivity for severe AKI = 42%; specificity for severe AKI = 85% Other options? Parikh et al. J Am Soc Nephrol 2011 Meersch et al. PLoS One 2014

13 Case series describing clinical use: Predicting injury Predicting recovery Guiding response to therapy

14 Can We Predict Pediatric AKI? Risk stratification of critically ill patients to develop AKI RAI >8 If renal angina present on day of ICU admit: Severe AKI likely on day 3 (AUC 0.8) Adding NGAL to model improved prediction (AUC 0.97) Basu et al. Kidney Int Menon et al. NDT 2016

15 Furosemide Stress Test FUROSEMIDE FUROSEMIDE hoat FST, 1mg/kg of furosemidein naive patients or 1.5 mg/kg in those with prior exposure Chawla et al. Crit Care 2013

16 Furosemide Stress Test AUC for the urine output 2 hrs after FST to predict progression to AKIN3 in 77 patients was 0.87 The ideal cutoff: urine volume of 200 ml (100 ml/hr) with a sensitivity of 87.1% and a specificity of 84.1%. FST outperformed any available biomarker In patients with increased biomarker levels, the AUC for progression to AKIN3 improved to 0.90 and the AUC for receipt of RRT improved to 0.91 Koyner, JASN 2015

17 Case #1: Continued With evidence of AKI and concerns for worsening status for this patient, RRT is indicated What RRT options do you have at your institution? What would you do for this patient, and why? How do you determine the dose of CRRT for this patient?

18 Pediatric CRRT Dose A lot of confusion Suggestions, but no prospective study Some literature from the adults Potentially no benefit from higher doses Potential harm deriving from higher doses

19 Common Approaches to CRRT Dose in Pediatric Patients 2000 ml/h/1.73m2 Based on paper describing nutritional issues in pediatric CRRT; later described with citrate anticoagulation for pediatric patients 25-35ml/kg/h Based on adult studies suggesting higher mortality with lower rates

20 2016 edizioni Minerva Medica the online version of this article is located at Minerva Pediatrica 2016 October;68(5): REVIEW dialytic dose in pediatric continuous renal replacement therapy patients Zaccaria ricci 1 *, Francesco GUZZi 2, Germana tuccinardi 3, 4, Stefano romagnoli 4, 5 66 papers from the year studies remaining 33 excluded (reviews and case reps) 13 excluded (no information on prescritpion) 11 retrospective, 4 case series, 9 prospective 4 retrospective papers only verified if delivered dialytic doses were significantly different in surviving and non surviving patients

21 2016 edizioni Minerva Medica the online version of this article is located at Minerva Pediatrica 2016 October;68(5): REVIEW dialytic dose in pediatric continuous renal replacement therapy patients Zaccaria ricci 1 *, Francesco GUZZi 2, Germana tuccinardi 3, 4, Stefano romagnoli 4, 5 Dose ranged from 1000 to 4000 l/h/1.73 m 2 and from 20 to 150 ml/kg/h. 1 study systematically analyzed the effect of pcrrt dose over time on serum markers such as creatinine and urea, and it showed that even a relatively small dose (35 ml/kg/h) was effective in controlling such molecules blood levels. 1 study analyzed the signicant loss of amino acids during PCRRT occurring at the standard prescription of 2L/h/1.73 m 2.

22 No Standard Recommendation for Pediatric CRRT Dose Ricci et al, Minerva Pediatrca 2016

23 Case #1: Further Questions Does your center have a formalized screening program or diagnostic plan for AKI? Which modalities of RRT do you use for AKI and how do you choose? How do you address the question of dose for CRRT?

24 Pediatric AKI and Dose of CRRT: Summary High prevalence of AKI in pediatric critical care More tools in toolbox to predict/clarify AKI Biomarkers Renal angina index Furosemide stress test CRRT has become a common practice for AKI but there is minimal literature on dose

25 Case #2 RRT FOR THE NEONATE

26 Case #2: Case Presentation 3 week old term female with perinatal asphyxia (abruption) and chorioamnionitis; looks septic Cr has been rising (1mg/dL à 3.2mg/dL) Weight increased (BW 3.2kg à 4.1kg); edematous Increased ventilator support; urine 1.1ml/kg/hr

27 Case #2: Questions Does this patient require renal replacement? What modality would be best for support? What issues and complications must we watch for if we go forward with renal replacement?

28 Renal Support Options Hemodialysis, Peritoneal Dialysis, CRRT Each has advantages & disadvantages Choice is guided by Patient Characteristics Disease/Symptoms Hemodynamic stability Goals of therapy Fluid removal Electrolyte correction Toxin removal Availability, expertise, cost Pediatr Nephrol (2009) 24:37 48

29 CRRT for Neonates: A Series of Challenges Small patient with small blood volume Equipment designed for bigger people No specific protocols Complications may be magnified No clear guidelines Limited outcome data

30 Prescribing CRRT: Special Neonatal Considerations Vascular access Blood Prime Blood flow rates Fluids/Modality (CVVH vs. CVVHD vs. CVVHDF) Ultrafiltration goals Anticoagulation Filter/membrane Device

31 Neonatal CRRT Access Access size is key to success Frequent clotting and circuit down time is time without therapy Vessel size Neonatal internal jugular vein ~3mm diameter 1 Fr = 0.33mm Low resistance Resistance ~8lη/2r4 So, the biggest and shortest catheter should be best

32 Smallest HD Catheters in US Temporary Catheter Medcomp Soft-Line 7Fr 10cm Medcomp Hemo-Cath LT 8Fr 18cm Remember: IJ diameter in a neonate is ~3mm 1Fr = 0.33mm Therefore... 7Fr = 2.31mm 8Fr = 2.65mm Tunneled Cuffed Catheter

33 Circuit Survival Curves by French Size of Catheter 5Fr Demise Hackbarth R et al: IJAIO December 2007

34 Blood Prime for Pediatric CRRT Blood prime supports BP, prevents hemodilution from saline prime Blood prime increases risk: Blood product exposure, possibly repeated HYPOCALCEMIA Citrate anticoagulant in PRBCs HYPERKALEMIA K+ release from RBCs ACIDEMIA Increases risk for bradykinin release syndrome Acute hypotensive event Associated with AN-69 membrane

35 Bypass System to Prevent Bradykinin Release Syndrome Blood Waste Modified from Brophy, et al. AJKD, 2001

36 Recirculation System to Prevent Bradykinin Release Syndrome Normalize ph Recirculation Plan: D Qb 200ml/min Qd ~40ml/min Time 7.5 min Normalize K + Based on Pasko, et al. Ped Neph 18: , 2003 Waste

37 Circuit-to-Circuit Prime NS

38 Simple Systems to Limit Likelihood of Bradykinin Release Syndrome Don t prime with blood Don t use the AN-69 membrane

39 Device Limitations for Infant CRRT

40 Infant-Specific/Adapted Devices Cardio Renal Pediatric Dialysis Emergency Machine (CARPEDIEM) Newcastle Infant Dialysis and Ultrafiltration System (NIDUS) Aquadex FlexFlow

41 CARPEDIEM: Cardio Renal Pediatric Dialysis Emergency Machine In use in Europe Smallest 1.1 kg Dedicated rather than adapted machine CVVH 3 sets: 27.2, 33.5, 41.5 ml ECV Ronco, Lancet, 2014 Lorenzin, Pediatr Nephrol, 2016

42 Newcastle Infant Dialysis and Ultrafiltration System (NIDUS) Single Catheter 9 cc extracorporeal volume Driven by syringes Uncoupled babys blood flow capacity from requirement of dialysis filter Promising results Description of 10 babies Coulthard, Pediatr Nephrol, 2014

43 Aquadex CRRT FDA approved in adults Fluid overload not responsive to diuretics 33 cc circuit volume CVVH Heparin anticoagulation Blood Flow: ml/min Smallest baby dialyzed: 1.2 kg Askenazi, Pediatr Nephrol, 2016

44 Case #2: Further Questions Do you perform CRRT for neonates at your center? What CRRT device do you use? What challenges and issues have you needed to address for these patients?

45 Neonatal CRRT: Summary Added technical challenges with small infants Careful consideration about risks/benefits for vascular access choices Most CRRT devices to date designed for adults but neonatalspecific devices becoming available PD remains an excellent option!

46 Case #3 CRRT AND ECMO

47 Case #3: Case Presentation 14 years old, previously healthy with h/o URI for 4-5 days, to PICU with hypoxic respiratory failure, sepsis, necrotizing pneumonia Intubated and then cannulated for VA-ECMO Weight (actual) 61.2kg Urine output dropping, serum creatinine rising 0.7mg/dL à 1.3mg/dL Worsening edema on exam PICU team contacts you regarding AKI and possible need for RRT

48 Case #3: Questions How do you address the need for RRT when a patient is on ECMO? What technical challenges must you anticipate? How do you coordinate care between teams? CRRT timing on ECMO? Do you have a protocol? Is it safe?

49 In-line hemofilter during ECMO Askenazi, CJASN 2012

50 CRRT Device with ECMO Santiago, KI 2009

51 CRRT and ECMO: Issues with the ECMO Circuit Negative Pressure CRRT circuit standard pressure mode Lower pressures, likely less pressure alarms Danger of AIR if disconnected Positive Pressure CRRT circuit positive pressure mode High ECMO pressures will influence CRRT pressures, likely more pressure alarms Danger of Exsanguination if disconnected

52 128 patients 2 weeks 17 years Survival 77% Duration of ECMO: 288 ± 240 hrs. RRT in 18 with 44% survival J Pediatr Surg Feb;35(2): Initiation Fluid Overload Discontinuation Survivors 9±2% 4±2% Non-Survivors 25±5% 35±7% Multivariable analysis: Renal Failure, inotropes, Failure to return to dry weight, lung compliance

53 5 year retrospective chart review (N=756) pediatric, 6 centers 380 received RST FO occurs commonly in this population Median peak FO on ECMO of 30.9% Peak FO: 10% in 85%; 20% in 67% and 50% in 29% Severe FO commonly occurs during ECMO and is associated with worse outcomes Mortality aor 1.18 for each 10% rise in peak FO FO also predicted length of ECMO Ped Crit Care Med, 2017

54 Neonates (31 neonates), historic comparison Implemented standard practice of CRRT 48 hrs. ECMO 97% on by 48 hours at median of 9 hours FO at CRRT initiation 0% vs 29% Early initiation associated with improved nutrition

55 Pediatr Crit Care Med Nov;14(9):e neonatal and pediatric patient, 458 serial measurements 12 integrated and 30 free-flow Compared ordered to achieved fluid balance for weight Findings: Integrated UF (device) more accurate Shorter duration of ECMO: 384 v 583 hrs. Shorter duration of RRT: 185 v 477 hrs.

56 Outcomes of CRRT and ECMO 153 cardiac patients : Evaluated the impact of Early CVVH (<48 hrs) on outcomes Primary indication for ecvvh à Fluid Overload 59 patients received ecvvh à Mortality 75% vs 40% Median age 13 days (57 days in ECMO alone) Multivariable analysis: ecvvh aor3.02 (95% CI, 1.3,6.9) ECPR, Postop status, Pre-ECMO creatinine, RACHS Ann Thorac Surg Sep;96(3):

57 Australian center, 86 patients (mixed population) Propensity score 1-1 matching ( demographics, diagnosis, pre- ECMO-Status, biochemistry) CVVH indication FO in 58% ECMO + CVVH: Improved fluid balance, longer ECMO duration No difference in survival Pediatr Crit Care Med Feb;16(2):161-6

58 10 year retrospective chart review 384 ECMO patients: 66% survival 154 ECMO/ CRRT patients, 68 survived : Survival 44% ECMO/ CRRT vs. 81% ECMO alone Longer duration Indication for CRRT FO 58% 28% of survivors required RRT after ECMO discontinuation 96% had renal recovery at discharge (MPA, ANCA vasc, sepsis) Pediatr Crit Care Med Mar;12(2):

59 Case #3: Further Questions Do you perform ECMO and CRRT at your center? What challenges and issues have you needed to address when considering RRT for patients receiving ECMO? Do you have a timing protocol? Has it been discussed?

60 CRRT and ECMO: Summary Increased complexity when combining extracorporeal therapies (CRRT and ECMO) CRRT monitor connected to ECMO appears to give more accurate ultrafiltration control than free-flow systems

61 Case #4 CRRT IN PEDIATRIC LIVER FAILURE

62 Case #4: Case Presentation 9yo male with maple syrup urine disease who underwent liver transplant 13 days prior. Complicated by thrombosis and failing graft. Currently relisted and has developed sepsis, respiratory failure, and oliguria. Failed diuretic challenges. Rising AST 4123, ALT 3757, Lactate 8. Poor synthetic function. Hyperbilirubinemia. Ammonia 245 Cr 0.8, Baseline 0.3 On epinephrine and norepinephrine Current weight 70.4kg, Admission weigh 61 kg Requiring frequent transfusions The decision is made to perform CRRT. Anticoagulation in liver failure? Dose?

63 Case #4: Questions What prescription/clearance challenges are posed by this patient? What are our options for anticoagulation?

64 Better survival with better ammonia control For every 10% decrease in NH3 from baseline at 48hrs, likelihood of survival increased by 50% For every 1hr delay initiating CRRT, likelihood of mortality increased by 4%

65 HVHF: >80ml/kg/hr led to improved hemodynamic stability and neurological status

66 Anticoagulation for Pediatric CRRT Heparin Decades of experience Systemic anticoagulation Risk of bleeding, HIT Variations in monitoring ACT, aptt, Xa Citrate Regional anticoagulation Risk of calcium or acidbase abnormalities, accumulation of citrate Somewhat more complex than heparin Other things? Direct thrombin inhibitors Prostacyclin Nothing?

67 Our approach to Liver Failure CRRT is the modality of choice in Fulminant liver failure What we know about these patients Frequently are paradoxically prone to clotting May require continuous fresh frozen plasma replacement Platelet infusions frequently Frequently will clot circuits without anticoagulation

68 Prospective observational study 28 patients with decompensated cirrhosis or acute liver failure CVVHD with RCA Blood flow 100, Qd 2000 Findings: Accumulation of citrate occurred without significant consequence Conclusion: CRRT in such patients is possible Critical Care, 2012

69 Retrospective chart review evaluating citrate toxicity in RCA in liver failure Over 30 months 51 patients on CRRT with liver failure CVVHDF dose 2000 ml/min/1.73 m 2 70% experienced citrate accumulation No increased adverse events Median filter life 66 hours Conclusion: RCA effective and safe in children with liver failure PLOS One, 2017

70 Case #4: Further Questions Do you make changes to your CRRT prescription for patient with liver failure? Do you individualize prescription/dose depending on the clinical situation?

71 CRRT in Liver Failure: Summary Pediatric acute liver failure patients are at high risk for complications Indications for CRRT may go beyond fluid and electrolyte balance Discussion with hepatology/transplant teams can help to clarify protocols

72 Case #5 CRRT IN THE OPERATING ROOM

73 Case #5 (a continuation of #4): Clinical Scenario 48 hours later our patient receives offer for liver transplant Surgeons request CRRT support in OR Fluid management Hyperkalemia

74 Case #5: Questions What technical considerations are posed? How are prescription and dosing choices affected by OR location?

75 Intraoperative CRRT: Goals Maximize circuit life Address/mitigate surgeon concerns Hyperkalemia Fluid Overload Avoid complexity Coordination with anesthesiologists Permit successful surgery and reasonable start to recovery

76 CRRT in the OR: Technical Discussion Staffing Dedicate RN for CRRT management MD for CRRT present at initiation; remains available Preparation IJ catheter is preferable Easier access if circuit is lost, troubleshooting Not affected by intraabdominal clamping and procedure Second circuit primed and ready outside OR

77 Prescription CRRT in the OR: Prescription and Anticoagulation Optimize Qb to prevent clotting Clearance: coordinate goals with anesthesiologists UF: consider fixed output for simplicity Anticoagulation Heparin vs. citrate anticoagulation Could consider no anticoagulation with NS flushes (50-250mL q30min)

78 Case #5: Further Questions Does your program provide RRT in the OR? What approach do you use? What challenges have you encountered with intraoperative RRT?

79 Case #5 Summary CRRT in the OR presents unique challenges Careful planning and coordination ahead of time is essential

80 Pediatric AKI & CRRT Part II HOW DO I CARE FOR MY PROGRAM?

81 Questions How do you train your team to perform CRRT effectively? How do you know you are being successful?

82 Your CRRT Program Standardization of Practice Guidelines Procedures Education Quality of Care Process Adherence to Standard Process of Delivering Care

83 Standardization of Practice Indications for therapy Initiation Procedures Circuit Changes Fluid Removal Calculation Documentation

84 Standard Practices Guidelines are DONE HOW DO YOU APPLY QI?

85 CPR Process Measures

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87 Prescribed Treatment Time Fluid Status at Initiation Definition: Quantified average of time for individual treatment. Measures: Prescribed: CRRT Start Date/Time to CRRT End Date/Time Filter Hours: Total hours filter is running Treatment Hours: Total hours filter is running and therapy being delivered

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90 CRRT Quality Improvement Measures Measure Category Value Program Activity Process Affect on QI measures Resilience of program/system Fluid Status at Initiation Process; Outcome SPG Adherence Deviation in process Time to Initiation Process SPG Adherence Availability of resources Filter Life and/or Survival Process Efficacy of anticoagulation Staff proficiency SPG Adherence Prescribed Dose Process Efficacy of anticoagulation Staff proficiency SPG Adherence Achievement of Fluid Goal Process Communication Staff knowledge SPG Adherence

91 Any Other Comments or Questions?

92 Thanks for Your Participation!