Pediatric CRRT The Basics

Transcription

1 Pediatric CRRT The Basics Patrick Brophy Geoffrey Fleming Jordan Symons Michael Zappitelli 16 th International CRRT Conference San Diego 2011

2 Epidemiology Of and Indications For Pediatric CRRT

3 ACUTE KIDNEY INJURY WHAT IS IT? HOW COMMON? WHO DOES IT HAPPEN TO? WHO GETS IT? CRRT WHAT DO THEY GET? WHO SHOULD GET IT?

4 Pediatric AKI: Definition Past: So many definitions. Risk Injury Failure End-Stage Kidney Disease (RIFLE) Pediatric RIFLE (prifle) Crit Care. 2005; 9(5): Acute Kidney Injury Network definition

5 Pediatric AKI: Incidence in PICU Population & Definition-dependent Cardiac Surgery N = 395 N=395 AKI: 34% No AKI R I F 0 No AKI R I F AKI: 21% Kidney Int Oct;76(8): Anesth Analg 2009;109:45 52 (Aprotinin study)

6 Pediatric AKI: Incidence in PICU Population & Definition-dependent General PICU Most Critically ill children Vasopressors/Ventilated Urinary catheter All PICU Admx SCr baseline All PICU stay>48hrs prifle 82% AKI No AKI R I F Kid Int 2007; 71: SCr Doubling (prifle I) <Doub SCr >=Doub SCr (Rifle I) 70% 60% 58% 4.5% AKI 50% 42% AKI 40% 30% 20% 10% 0% prifle 16% 17% 9% No AKI Stage 1 Stage 2 Stage 3 Pediatr Crit Care Med 2007; 8:29 35 Al-Kandari et al, ASN, 2008

7 Pediatric AKI: Changing Epidemiology Previously: Primary renal diseases Number of Patients Pediatric ARF Causes Unknown AGN Hemoglobinuria Sepsis Hem Cystitis ATN-Dehyrdation Congenital Heart Fluid Overload Neoplasm Low Alb HUS Chronic Renal Dz Congestive heart Rhabdomyolysis ARDS Pyelonephritis Vasculitis Nephrotoxic Med Stickle SH et al: Am J Kid Dis 45:96-101, 2005

8 CRRT Diagnoses

9 RRT 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 Both Availability, expertise and cost Pediatr Nephrol (2009) 24:37 48

10 Trends in Pediatric RRT CRRT Increasing 12-US Multicentre ppcrrt Most include Dialysis 60% 50% 40% 30% 20% CRRT PD HD 10% 0% Warady et al, Pediatr Neph 2000, 15:11-3

11 Why CRRT? Reduces hemodynamic instability preventing secondary ischemia Precise Volume control/immediately adaptable Uremic toxin removal Effective control of uremia, hypophosphatemia, hyperkalemia Acid base balance Rapid control of metabolic acidosis Electrolyte management Control of electrolyte imbalances Allows for improved provision of nutritional support Management of sepsis/plasma cytokine filter Safer for patients with head injuries

12 Indications for Pediatric RRT Electrolyte (metabolic) imbalance Uremia with bleeding and or encephalopathy Acuity/Degree of Kidney Injury reduction in GFR/elevated creatinine reduction in urine output Nutritional support Intoxications, Inborn errors of Metabolism (IEM) Fluid Overload (hypervolemia with pulmonary edema/respiratory failure)

13 Fluid Overload P<0.05 Independently associated with mortality in children at CRRT initiation.

14 Timing of Pediatric RRT????????? AKI definition may help. The decision to initiate RRT affected by strongly held physician beliefs Patient characteristics : age, race, illness acuity, and co-morbidities. Considerations Emerging importance of fluid overload prevention. Children develop MODS early in ICU course Maximum number of organ failures occurs within 72 hours of ICU admission (87% of patients) Organizational characteristics Children die with MODS very early in ICU course 88.4% of deaths occur within 7 days of MOSF diagnosis Proulx et al: Crit Care Med 22:1025, 1994

15 Children are not small adults 0 days to 21+ years 2 kg to 200 kg Not present Diabetes Older age Atherosclerotic disease Hypertension Volume of patients Present Size/Access variation Less frequent than adults/less experience Machinery is adapted (not made) for pediatrics Blood priming UF, thermic controls

16 Summary: Pediatric CRRT Epidemiology and Indications Pediatric AKI may be more common than previously described Primary renal disease giving way to MODS CRRT for children continues to expand Advantageous in critically ill child Effective therapy for renal failure Useful in setting of volume overload Best time to start remains uncertain Better AKI definitions will help answer??s

17 CRRT Terminology and Modalities

18 Diffusion vs. Convection Diffusion is solute transport across a semi-permeable membrane - molecules move from an area of higher to an area of lower concentration Effective for small molecule clearance Convection is a process where solutes pass across the semipermeable membrane along with the solvent in response to a positive transmembrane pressure Effectiveness less dependent on molecular size

19 Current Nomenclature for CRRT SCUF: CVVH: CVVHD: CVVHDF: Slow Continuous Ultrafiltration Continuous Veno-Venous Hemofiltration Continuous Veno-Venous Hemodialysis Continuous Veno-Venous Hemodiafiltration

20 CRRT Schematic R SCUF CVVH D CVVHD UF CVVHDF

21 CRRT Machines

22 Convection vs. Diffusion Are there advantages of one type of therapy over another? Solute (MW) Convective Coefficient Diffusion Coefficient Urea (60) 1.01 ± ± 0.07 Creatinine (113) 1.00 ± ± 0.06 Uric Acid (168) 1.01 ± ± 0.04* Vancomycin (1448) 0.84 ± ± 0.04** Cytokines (large) adsorbed minimal clearance *P<0.05, **P<0.01

23 Urea Clearance: CVVHD vs Pre-Dilution CVVH Parakininkas and Greenbaum, Ped Crit Care Med 2004

24 PreDilution CVVH vs CVVHDF: Effect on Solute Clearances Troyanov et al, Nephrol Dial Transplant 2003

25 Urea Clearance (mls/min/1.73 m2) Urea Clearance: CVVH vs CVVHD (Maxvold et al, Crit Care Med April 2000) p = NS 0 CVVH CVVHD BFR = 4 mls/kg/min FRF/Dx FR = 2 l/1.73 m2/hr SAM = 0.3 m2

26 Summary: CRRT Terminology and Modalities CRRT employs physical principles of diffusion and/or convection Nomenclature depends on methods used SCUF, CVVH, CVVHD, CVVHDF All methods that employ solutions are effective at removing small molecules Convection improves large particle removal Still unclear about best modality

27 Vascular Access and Anticoagulation for Pediatric CRRT

28 Why Access function is crucial for therapy Flows obtained will affect adequacy of blood flow for dose delivered and can affect filtercircuit life Downtime from clotted circuits-access is time off therapy

29 Access Considerations Low resistance Resistance ~ 8lη/2r 4 So, the biggest and shortest catheter should be best Vessel size French ~ 3 x diameter of vessel Beside ultrasound nearly universal SVC is bigger than femoral vein

30 Access Considerations Internal Jugular Very accessible Large caliber (SVC) Great flows Low recirculation rate Risk for Pneumothorax Cardiac monitoring may take precedence. Femoral Usually accessible Smaller than SVC Flows may be diminished by: Abdominal Pressures Patient movement Risk for retroperitoneal hemorrhage Higher recirculation rate Subclavian: Many feel current double lumen vas cath are too stiff to make the turn into the SVC and I don t personally use them. Although they are used in some centers. Better for bigger kids likely.

31 376 Patients 1574 circuits Femoral 69% IJ 16% Sub-Clavian 8% Not Specified 7%

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

33 Summary: Vascular Access for Pediatric CRRT Put in the largest and shortest catheter when possible Caveat: short femoral catheters have been shown to have high rate of recirc in adult patients. (Little et al. AJKD 2000;36:1135-9) The IJ site is preferable (over femoral) when clinical situation allows Avoid double lumen 5Fr Catheters 2 site single lumen 5Fr catheters ok

34 Anticoagulation Another crucial step in delivering the prescribed dose (reducing downtime) Critically ill patients are at risk for both increased and decreased clot formation simultaneously

35 Heparin acts in conjunction with ATIII on thrombin and F IX, FX, FXII Calcium is necessary for each event in the cascade.

36 The Clot

37 What the filter looks like Hofbauer R et al. Kid Int 1999;56: Heparin Citrate Electron microscopy of polysulfone hemodiafilter with two varieties of anticoagualtion during IHD. Granted, no monitoring of degree of anticoagulation was performed to assess adequacy of response.

38 Anticoagulation Systemic Heparin Goal ACT sec Patient anticoagulated Risk of bleeding Risk for HIT Regional Citrate Goal Circuit ical mmol/L Goal Patient ical mmol/l Risk for Hypocalcemia Alkalosis Hypernatremia

39 138 Patients in multicenter registry study 442 Circuits Circuit survival time evaluated for three anticoagulation strategies Heparin (52% of circuits) Regional Citrate (36% of circuits) No anticoagulation (12% of circuits)

40 Brophy PD et al. Nephrol Dial Transplant. 2005;20: Mean circuit survival (42 and 44 hr) were not different for Hep vs Citrate, but both longer than no anticoagulation (27 hr) At 60 hr, 69% of Hep and Citrate circuits were functional, but only 28% of the noanticoagulation circuits In this analysis circuit survival was not affected by the access size Citrate group had no bleeding complications, 9 Heparin patients with bleeding

41 Citrate Specific Issues Alkalosis 1 mmol Citrate to 3 mmol HCO3 Normocarb protocols may exacerbate (35 meq/l) Hypernatremia Tri-Sodium Citrate infusion Hypocalcemic Citrate Toxicity Incomplete clearance of citrate, usually due to liver dysfunction Rising total calcium, decreasing ical

42 Citrate Specific Issues Alkalosis and Hypernatremia Increase diffusion clearance (increase dialysate flow) Or substitute normal saline for some of the high bicarb containing dialysate Others use pharmacy made citrate solutions with 0.67% Citrate vs 2% standard citrate solution (Tolwani AJ et al. Clin J Am Soc Nephrol 2006;1:79-87)

43 Hypocalcemic Citrate Toxicity Rising Total Calcium Declining ical Usually see with infants (more Qb hence citrate than total clearance) and in those with liver failure Risk for severe hypocalcemia Rx by decreasing citrate, and/or a period of increased clearance (D or UF)

44 Summary: Anticoagulation for Pediatric CRRT Heparin or Citrate is better than no anticoagulation (even in liver failure, DIC, etc) Citrate has fewer bleeding complications Circuit survival means less downtime hence more delivered therapy Pick institutional strategy and learn to use it well Consider citrate as the method of choice

45 Prescribing Pediatric CRRT

46 Prescribing Pediatric CRRT Vascular access Hemofilter Prime Blood pump speed (Q B ) Anticoagulation Ultrafiltration rate Infused fluids CVVH: Pre- and/or post-dilutional replacement CVVHD: Counter-current dialysate CVVHDF: Dialysate and replacement fluid

47 Hemofilter for CRRT Hemofilter size Volume, porosity Membrane material Polysulfone, AN-69, PAES, etc. Tubing set integrated or separate? Open vs. closed systems do you have a choice?

48 Blood Priming the Circuit for Pediatric CRRT Small patient, large extracorporeal volume Albumin Hemodynamic instability Saline Common default approach Self Volume loaded renal failure patient

49 Choosing Q B for Pediatric CRRT Choose blood flow rate (Q B ) of 3-5ml/kg/min, or: 0-10 kg: 25-50ml/min 11-20kg: ml/min 21-50kg: ml/min >50kg: ml/min CRRT device may affect choices for Q B The real determinant the vascular access

50 Ultrafiltration in Pediatric CRRT Choose UF rate to balance input remove excess fluid over time make room for IV fluids and nutrition provide solute clearance by convection SCUF, CVVHD, post-dilution CVVH: UF rate may be limited by blood flow (filtration fraction) Pre-dilution CVVH: High flow of pre-dilution fluid lessens hemoconcentration Remember to consider UF limits of the filter, especially in higher-volume hemofiltration

51 Infused Fluids for Pediatric CRRT SCUF: No infused fluids CVVHD: Counter-current dialysate CVVH: Pre- and/or post-dilution replacement fluid CVVHDF: Dialysate and replacement fluids

52 Rate for Infused Fluid Higher rates increase clearance Lower rates may simplify electrolyte balance and limit protein loss Equations to help choose rate for fluid: ml/kg/hr ml/hr/1.73m 2 May need higher rates to balance citrate delivery

53 Dialysate / Ultrafiltration Rates No Study has identified effective, safe UF or dialysate flow rates in Children. For HEMODIALYSIS NET UF rate of 0.2ml/kg/min is tolerated This extrapolates to 1 ml/kg/ hr (NET UF) over 48 hr of continuous hemofiltration. Donckerwolke Ped Neph 8: ,1994

54 Summary: Prescribing Pediatric CRRT Consider needs for vascular access, hemofilter, priming of circuit, blood pump speed (Q B ), anticoagulation, UF goals, and infused fluids Choices may depend on clinical status of the patient and capabilities at your facility Coordination with all members of the critical care team is essential

55 Solutions for Pediatric CRRT: Dialysis Fluids and Replacement Fluids

56 Characteristics of the Ideal CRRT Solution Physiological Reliable Inexpensive Easy to prepare Simple to store Quick to the bedside Widely available Fully compatible

57 Purpose of CRRT solutions Provide safe and consistent metabolic control To be adaptive to the choice of therapy- CVVH vs CVVHD

58 Options for CRRT Solutions Peritoneal dialysate: Pre-made IV solutions: Saline, Lactated Ringers Multi-bag systems: Custom-made solutions: Local pharmacy; outsource NO MAYBE UNNECESSARY RARELY Commercially available CRRT solutions

59 Evaluation of Errors in Preparation of CRRT Solutions Survey of 3 Pediatric Listserves: Pediatric Critical Care Pediatric Nephrology Pediatric CRRT 31 programs responded to query Barletta JF et.al Pediatr Nephrol Jun;21(6):842-5

60 Prevalence and Consequences of Errors in Solution Preparation 16/31 programs reported errors: 7 errors in replacement solutions 9 errors in dialysate solutions Consequences of improper solutions 2 deaths 1 non lethal cardiac arrest 6 seizures (hypo/hypernatremia) 7 without complications Barletta JF et.al Pediatr Nephrol Jun;21(6):842-5

61 Policy Changes Resulting from Errors in Solutions Changed to Normocarb for either replacement or dialysate (11) Changed to PrismaSate for dialysate (2) Purchased TPN mixer for solutions (2) Chemistry lab check of every bag (3) Bag label check by at least 2 staff (10) Barletta JF et.al Pediatr Nephrol Jun;21(6):842-5

62 What s the Difference Between Dialysate and Replacement Fluid? Dialysate is a Device Replacement Fluid is a Drug

63 CRRT Solutions Many Choices Name Company R / D Bag Size* Flavors Normocarb HF DSI R 3.24 L 2 Prismasate Gambro D 5 L 6 Accusol Baxter D 2.5 L 5 Prismasol Gambro R 5 L 7 Duosol B Braun D 5 L 6 PureFlow NxStage D 5 5 *after mixing

64 Summary: CRRT Solutions Solutions needed to maximize clearance Pharmacy made solutions give greatest flexibility but have increased risks/costs Several industry-made solutions two currently approved for replacement

65 Outcome/ Demographics

66 Pediatric Acute Renal Failure: Ideal Study Design Prospective protocol driven entry criteria to ensure that patients and their respective disease receive similar treatment --- Do not exist! Control for severity of illness, primary and comorbid diseases --- Some information Adequate power to detect effect of an intervention on or an association of a clinical variable with outcome --- Do not exist!

67 Retrospective evaluation of 226 children who received RRT for AKI from Pressor use surrogate marker for patient severity of illness Survival defined at PICU discharge

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69 Retrospective review of all patients who received CVVH(D) in the Texas Children s Hospital PICU from February 1996 through September 1998 (32 months) Pre-CVVH initiation data: Age Primary disease leading to need for CVVH Co-morbid diseases Reason for CVVH Fluid intake (Fluid In) from PICU admission to CVVH initiation Fluid output (Fluid Out) from PICU admission to CVVH initiation GFR (Schwartz formula) at CVVH initiation

70 Percent Fluid Overload Calculation % FO at CVVH initiation = [ Fluid In - Fluid Out ICU Admit Weight ] * 100% Fluid In = Total Input from ICU admit to CRRT initiation Fluid Out = Total Output from ICU admit to CRRT initiation

71 22 pt (12 male/10 female) received 23 courses (3028 hrs) of CVVH (n=10) or CVVHD (n=12) over study period. Overall survival was 41% (9/22). Survival in septic patients was 45% (5/11). PRISM scores at ICU admission and CVVH initiation were /- 5.7 and /- 9.0, respectively (p=ns). Conditions leading to CVVH (D) Sepsis (11) Cardiogenic shock (4) Hypovolemic ATN (2) End Stage Heart Disease (2) Hepatic necrosis, viral pneumonia, bowel obstruction and End-Stage Lung Disease (1 each)

72 Survival curve demonstrates that nearly 75% of deaths occurred less than 25 days into the ICU course Cumulative Proportion Surviving Survival Time (days)

73 Lesser % FO at CVVH (D) initiation was associated with improved outcome (p=0.03) Lesser % FO at CVVH (D) initiation was also associated with improved outcome when sample was adjusted for severity of illness (p=0.03; multiple regression analysis) %FO at CVVH Initiation Death p = 0.03 Survival Mean+SE Mean-SE Mean OUTCOME

74 N=113 *p=0.02; **p=0.01

75 N = 77 Group Fluid Overload Hazard Ratio (95% CI) P All Subjects <10% 1 >10% 3.02 ( ) 0.002

76 Kaplan-Meier survival estimates, by percentage fluid overload category

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80 The Evolution of Idea to Practice Paradigm:The ppcrrt Registry Group Michael Somers Michelle Baum Cheryl Baker Theresa Mottes Jordan Symons Nancy McAfee Tim Bunchman Rick Hackbarth Dawn Eding Mark Benfield David Askenazi James Fortenberry Kristine Rogers Renee Robinson John Mahan Deepa Chand Francisco Flores Kevin McBryde Steven Alexander Annabelle Chua Douglas Blowey Stuart Goldstein (Founder)

81 Prospective Pediatric CRRT (ppcrrt ) Registry: Phase 1 Design Collect prospective data from 10 pediatric centers treating 15 to 20 patients annually (376 patients over 5 years) Each center follows own institutional practice Patient selection Initiation and termination Anti-coagulation protocols Convection versus diffusion versus hemodiafiltration Fluid composition

82 Overall Survival rate 58%

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85 Seven center study from the ppcrrt Registry 116 patients with MODS PRISM 2 score used to assess patient severity of illness Survival defined at PICU discharge

86 ppcrrt FO Threshold: Multivariate analysis Variable Fluid Overload Group 20% FO vs. <10% FO 20% FO vs. 10%-20% FO 10%-20% FO vs. <10% FO Odds Ratio (Mortality) % Confidence Interval p-value < Oncologic Diagnosis <0.001 Diagnosis of MODS Sepsis Diagnosis Convective CRRT Modality PRISM II PICU Admission IEM/Intoxication Diagnosis Inotrope Number CRRT Initiated to treat FO Age at CRRT Initiation Sex Sutherland S. for the ppcrrt: Am J Kidney Dis Feb;55(2):

87 Mortality Rate 100% 90% 80% 70% 60% 50% 40% 30% 20% 10% 0% 36.7% 22.1% 29.4% ppcrrt FO Threshold: Multivariate analysis 43.1% 10% Fluid 10%-20% Fluid Overload Sutherland S. for the ppcrrt: Am J Kidney Dis Feb;55(2): % 29.1% 75.4% 55.8% 65.6% 20% Fluid Overload

88 Stem Cell Transplant: ppcrrt 51 patients in ppcrrt with SCT Mean %FO = %. 45% survival Convection: 17/29 survived (59%) Diffusion: 6/22 (27%), p<0.05 Survival lower in MODS/ventilated patients Flores FX et al: Pediatric Nephrology

89 Percent survival Survival Based on CRRT Modality Pediatric Stem Cell Transplant Recipients P < 0.05 CVVH + CVVHDF CVVHD Flores FX et. al Peds Neph (in Press)

90 ppcrrt & SCT Variable Survivors Non-survivors p Value Patient Admit Age (yr) NS Patient Admit Weight (kg) NS Patients kept dry prior to CRRT initiation No difference in any parameter at CRRT initiation Paw worse for nonsurvivors at CRRT end PRISM 2 at PICU admit PICU Days to CRRT Initiation NS PRISM 2 at CRRT Initiation CRRT Initiation GFR (ml/min/1.73) NS %FO at CRRT Initiation NS No. Inotropes at CRRT Initiation CVP at CRRT Initiation NS Paw at CRRT Initiation (mmh 2 O) NS Paw at End CRRT (mmh 2 O) <0.001 Urine Output (ml/kg/hr) NS CRRT Duration (day) NS Filtration (ml/min/1.73 m 2 ) NS Flores FX et al: Pediatric Nephrology in press

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92 Ronco, Lancet, 2000 The Ronco Study Improved survival in all patients with convective clearance of 35mL/kg/hr Trend towards improved survival in septic patients with convective clearance of 45mL/kg/hr

93 The ATN Study 1124 adults in the ICU 563 had intensive therapy 561 had less-intensive therapy

94 ATN Study

95 ATN Study

96 Intensity of CRRT in Critically Ill Patients (The RENAL Study) NEJM 361(17); Oct 2009

97 Intensity of CRRT in Critically Ill Patients (The RENAL Study) NEJM 361(17); Oct 2009

98 CRRT Associated Mortality in Major RCT s Borrowed with permission from Claudio Ronco M.D. Clinical Trial Comparison APACHE II Endpoint Mortality Ronco 2000 CRRT dose day 59% Mehta 2001 IHD vs. CRRT 25.5 Hospital 66% Augustine 2004 IHD vs. CRRT - Hospital 68% Saudan 2006 CRRT dose Day 66% Vinsonneau 2006 IHD vs. CRRT day 68% Lins 2008 IHD vs. CRRT 27 Hospital 58% Tolwani 2008 CRRT dose 26 Hospital 60% ATN 2008 Dialysis Dose day 52.5% RENAL 2009 CRRT dose day 45%

99 Pediatric CRRT Associated Mortality Clinical Trial Study design N PRISM Survival Goldstein et al Pediatrics 2001 Gillespie et al. Ped Neph 2004 Foland et al PCCM 2004 Symons et al CJASN 2008 Hayes et al. JCC 2009 Retrospective % Retrospective % Retrospective % ppcrrt Registry % Retrospective

100 BUN at initiation of RRT Predialysis BUN Mortality (%) Early Late Early Late Parson 61 > Fischer Kleinknecht Conger Gettings Bouman Liu >

101 Fluid Accumulation and Survival Bouchard J, et al. Kidney International 2009

102 Fluid Overload in IHD vs. CRRT PICARD study Bouchard J, et al. Kidney International 2009

103 Outcomes after pediatric AKI Hospital Survival of Pediatric AKI 176 / 245 ( 72% ) hospital survival 3-5 year Follow-up Survival Additional 37 children die 139 / 245 (58%) of the original cohort Renal Dysfunction 29 patients 59 % had at least one of the following» HTN, CKD and/ or microalbuminuria 1. Arikan A, et al. Kidney International Hui-Stickle S, et al: Am J Kidney Dis June Askenazi DJ et al. Kidney International January 2006

104 Approach to Pediatric AKI EGDT Defend Blood Pressure Restore & Optimize Perfusion Use inotropes with care Mitigate Inflammatory Injury Optimize RRT Normal Increased risk Damage GFR Kidney failure Death Antecedents Intermediate Stage AKI Outcomes

105 Reference Tools Adqi.net-web site for information on CRRT Crrtonline.com-web site for info on Dr Mehta s meeting Pediatric CRRT with links to other meetings, protocols, industry 5th International Conf on Pediatric CRRT June 19-21, 2008 Orlando, Florida PCRRT list serve (contact Bunchman)

106 Thanks ppcrrt members Dr. Ravi Mehta Bedside ICU and Dialysis Nurses