20 years of PCRRT:20 years of PCRRT: changing indications and diagnoses ?changing indications and diagnoses ?

Ekkehard RingEkkehard RingDepartment of PediatricsDepartment of Pediatrics

Medical University of GrazMedical University of Graz

AustriaAustria

Historical background of pediatric continuous Historical background of pediatric continuous renal replacement therapy (PCRRT)renal replacement therapy (PCRRT)

• 19771977 Kramer et al. Klin. Wochenschr. Kramer et al. Klin. Wochenschr.– First report of arteriovenous hemofiltration First report of arteriovenous hemofiltration

(CAVH) in adult patients(CAVH) in adult patients

• 19861986 Ronco et al. Kidney Int. Ronco et al. Kidney Int.– Four critically ill neonates with ARF and Four critically ill neonates with ARF and

successful CAVH-treatmentsuccessful CAVH-treatment

• Starting point for intensified development Starting point for intensified development in PCRRTin PCRRT

In Graz: first CAVH 05/1985 In Graz: first CAVH 05/1985 Diabetic coma, rhabdomyolysisDiabetic coma, rhabdomyolysis

Development of pediatric continuous renal Development of pediatric continuous renal replacement therapy (PCRRT)replacement therapy (PCRRT)

• „„Self-made“ arteriovenous devices and circuits Self-made“ arteriovenous devices and circuits (CAVH)(CAVH), partially with suction support, partially with suction support

• Addition of dialysate countercurrentAddition of dialysate countercurrent– Hemodiafiltration Hemodiafiltration (CAVHDF)(CAVHDF)

Development of pediatric continuous renal Development of pediatric continuous renal replacement therapy (PCRRT)replacement therapy (PCRRT)

• Pump-assisted veno-venous devicesPump-assisted veno-venous devices– CVVH, CVVHDFCVVH, CVVHDF– Initially leading to hemodynamic instabilityInitially leading to hemodynamic instability– Inaccuracies of blood flow and ultrafiltrationInaccuracies of blood flow and ultrafiltration

Development of pediatric continuous renal Development of pediatric continuous renal replacement therapy (PCRRT)replacement therapy (PCRRT)

• Improvement of Improvement of – Vascular catheters, hemofilters, blood linesVascular catheters, hemofilters, blood lines– Accuracy of pumps for blood flow and UFAccuracy of pumps for blood flow and UF– Replacement solutions (bicarbonate)Replacement solutions (bicarbonate)– Anticoagulation (regional, citrate) Anticoagulation (regional, citrate) Minimizing bleeding riskMinimizing bleeding risk

Development of pediatric continuous renal replacement therapy (PCRRT)

Nowadays• High sophisticated automatic

devices enabling the optimal technical support for critically ill children and neonates with ARF and need for RRT

• Further development needed– Devices for neonates and

prematures– Optimal dosage of HF, HDF

Method of choice for acute RRT ?Method of choice for acute RRT ?

• Questionnaire survey among nephrologistsQuestionnaire survey among nephrologists

• „ „ ...CRRT will soon be used at virtually all ...CRRT will soon be used at virtually all pediatric centers“.pediatric centers“.

• European GuidelinesEuropean Guidelines– Strazdins et al. Pediatr Nephrol 2004; 19:199Strazdins et al. Pediatr Nephrol 2004; 19:199– „„choice of dialysis depend upon clinical circumstancies, location of choice of dialysis depend upon clinical circumstancies, location of

the patient, and expertise available... the patient, and expertise available... Hemofiltration increasingly Hemofiltration increasingly employed in the intensive care situationemployed in the intensive care situation““

CRRTCRRT PDPD HDHD

Belsha 1995Belsha 1995 18%18% 45%45% 38%38%

Warady 1999Warady 1999 36%36% 31%31% 33%33%

Indications for RRTIndications for RRT• Acute renal failure (ARF)Acute renal failure (ARF) PD, HD, HF available PD, HD, HF available

– Primary renal disordersPrimary renal disorders (isolated ARF) (isolated ARF)• Extremely low mortality rate (HUS as most frequent diagnosis)Extremely low mortality rate (HUS as most frequent diagnosis)

– ARF as part of multiple organ system failure (MOSF)ARF as part of multiple organ system failure (MOSF)

• Chronic renal failure (CRF)Chronic renal failure (CRF)– PD, HD,PD, HD, intermittent use of CRRT (HDF) ?intermittent use of CRRT (HDF) ?– At least 2 of 3 modalities needed in large pediatric clinicsAt least 2 of 3 modalities needed in large pediatric clinics– Cost effectiveness of HD-Units in smaller centersCost effectiveness of HD-Units in smaller centers– CRRT being established in an open pediatric ICUCRRT being established in an open pediatric ICU– HF (HDF) as treatment for CRF to be consideredHF (HDF) as treatment for CRF to be considered

• A time for rediscovery: chronic hemofiltration for end-stage renal A time for rediscovery: chronic hemofiltration for end-stage renal disease. McCarthy et al. Semin Dial (2003) 16:199disease. McCarthy et al. Semin Dial (2003) 16:199

Non-renal indications for CRRTNon-renal indications for CRRT

• Metabolic crisis - inborn errors of metabolismMetabolic crisis - inborn errors of metabolism– Organic acidurias, Urea cycle disorders (hyperammonemia)Organic acidurias, Urea cycle disorders (hyperammonemia)

– Rapid elimination of toxic metabolitesRapid elimination of toxic metabolites

– Disease specific treatmentDisease specific treatment

• CVVHDF treatment of choiceCVVHDF treatment of choice (Highest clearance rates)(Highest clearance rates)

– Outcome correlates with rapid elimination rateOutcome correlates with rapid elimination rate» Schäfer et al. NDT 1999; 14:910Schäfer et al. NDT 1999; 14:910

– Outcome correlates with coma duration before CRRTOutcome correlates with coma duration before CRRT» Picca et al. Pediatr Nephrol 2001; 16:862Picca et al. Pediatr Nephrol 2001; 16:862

• Intoxications with drugsIntoxications with drugs• SepsisSepsis

– With or without ARF, HF-dosage, removal of mediators ....With or without ARF, HF-dosage, removal of mediators ....

Non-renal indications for CRRTNon-renal indications for CRRT

• Liver support in fulminant hepatic failureLiver support in fulminant hepatic failure– Molecular Adsorbents Recycling System (MARS)Molecular Adsorbents Recycling System (MARS)

– Promising resultsPromising results

– Open for discussionOpen for discussion• Tissieres et al. Liver support for fulminant hepatic failure: is it time Tissieres et al. Liver support for fulminant hepatic failure: is it time

to use the molecular adsorbents recycling system in children? to use the molecular adsorbents recycling system in children? Pediatr Crit Care Med 2005; 6:616Pediatr Crit Care Med 2005; 6:616

• Tumor lysis syndromeTumor lysis syndrome– Significant cause of morbidity and mortality in oncologySignificant cause of morbidity and mortality in oncology

– Continuous, massive release of intracellular solutesContinuous, massive release of intracellular solutes

– CRRT is the method of choiceCRRT is the method of choice

– „„preventive CRRT“ in high-risk patientspreventive CRRT“ in high-risk patients

Outcome after CRRTOutcome after CRRTChange of overall mortality rate ?Change of overall mortality rate ?

• 9 publications (1x 1995), 2000-05 and own data9 publications (1x 1995), 2000-05 and own data

• Mortality rates 32% - 89% (21 – 226 children)Mortality rates 32% - 89% (21 – 226 children)• 416 / 834 non-survivors = mortality rate 50%416 / 834 non-survivors = mortality rate 50%• Data divided by 3 time-periods of patient samplingData divided by 3 time-periods of patient sampling

No. of patientsNo. of patients Non-survivorsNon-survivors Mortality rateMortality rate

1985-19941985-1994 247247 150150 61 %61 %

1992-19981992-1998 277277 138138 50 %50 %

1995-20041995-2004 310310 128128 41 %41 %

Long-term surveys of ARF / RRTLong-term surveys of ARF / RRTTrends in diagnoses and outcomeTrends in diagnoses and outcome

• Just 1 single-center studyJust 1 single-center study– Williams et al. Arch Pediatr Adolesc Med (2002) 156:893Williams et al. Arch Pediatr Adolesc Med (2002) 156:893

• Retrospective examination 1979 – 1998 Retrospective examination 1979 – 1998 • divided in 2 periods 1979-1988 and 1989-1998divided in 2 periods 1979-1988 and 1989-1998

• 228 children with ARF228 children with ARF– Admission to PICU: n = 154 (68%)Admission to PICU: n = 154 (68%)

• Acute RRT: n = 93 (41%) Acute RRT: n = 93 (41%) [60% of PICU admission][60% of PICU admission]

• ARF-mortality rate 27% ARF-mortality rate 27% (no difference between decades)(no difference between decades)

– Mortality rate of 67% in patients with RRTMortality rate of 67% in patients with RRT

Long-term surveys of ARF / RRTLong-term surveys of ARF / RRTTrends in diagnoses and outcomeTrends in diagnoses and outcome

• Study of Williams et al. Arch Pediatr Adolesc Med (2002) 156:893Study of Williams et al. Arch Pediatr Adolesc Med (2002) 156:893

• CRRT starting in the second decade (14% of RRT)CRRT starting in the second decade (14% of RRT)

• Unchanged between decades:Unchanged between decades:– HUS as leading diagnosis with favourable outcome (2% mortality)HUS as leading diagnosis with favourable outcome (2% mortality)

– Young age < 1 y represents 57% of non-survivorsYoung age < 1 y represents 57% of non-survivors

• Changes between decades:Changes between decades:– Cardiac surgery main and increasing cause of death (27% >> 44%)Cardiac surgery main and increasing cause of death (27% >> 44%)

– Decreasing mortality rate in sepsis and burnsDecreasing mortality rate in sepsis and burns

– Oncologic complications increasingOncologic complications increasing• No death with tumor lysis syndrome in the second decadeNo death with tumor lysis syndrome in the second decade

• Complications with bone marrow transplantation as new diseaseComplications with bone marrow transplantation as new disease

20 years of PCRRT in Graz (1985 – 2004)20 years of PCRRT in Graz (1985 – 2004)

• Retrospective analysis of 115 consecutive childrenRetrospective analysis of 115 consecutive children• Two periods (1985-1994 and 1995-2004)Two periods (1985-1994 and 1995-2004)

• Decreasing incidence of CRRT in the second decadeDecreasing incidence of CRRT in the second decade

• Decreasing mortality rate aside from infantsDecreasing mortality rate aside from infants

1985-19941985-1994 1995-20041995-2004 TotalTotal

Patients Patients ((mortality ratemortality rate))

87 (45%)87 (45%) 28 (39%)28 (39%) 115 (43%)115 (43%)

Age < 1yAge < 1y 42 (38%)42 (38%) 8 (88%)8 (88%) 50 (46%)50 (46%)

Age 1-6 yAge 1-6 y 24 (42%)24 (42%) 14 (29%)14 (29%) 38 (37%)38 (37%)

Age 6-18 yAge 6-18 y 21 (62%)21 (62%) 6 ( 0%)6 ( 0%) 27 (48%)27 (48%)

20 years of PCRRT in Graz (1985 – 2004)20 years of PCRRT in Graz (1985 – 2004)

• Underlying disorders Underlying disorders [No. of patients (mortality rate)][No. of patients (mortality rate)]

1985-19941985-1994 1995-20041995-2004 TotalTotal

primary renal primary renal diseasedisease

8 (12%)8 (12%) 5 (0%)5 (0%) 13 (8%)13 (8%)

cardiac cardiac surgerysurgery

39 (43%)39 (43%) 10 (60%)10 (60%) 49 (47%)49 (47%)

sepsissepsis 14 (43%)14 (43%) 6 (50%)6 (50%) 20 (45%)20 (45%)

oncologiconcologic 13 (92%)13 (92%) 2 ( 0%)2 ( 0%) 15 (50%)15 (50%)

metabolicmetabolic 7 (14%)7 (14%) 2 (50%)2 (50%) 9 (25%)9 (25%)

burnsburns 3 (0%)3 (0%) 00 3 (0%)3 (0%)

20 years of PCRRT in Graz (1985 – 2004)20 years of PCRRT in Graz (1985 – 2004)• Changes of CRRT techniqueChanges of CRRT technique

– Period 1: 75% treated with CAVH or CVVHPeriod 1: 75% treated with CAVH or CVVH– Period 2: 75% treated with CVVHDFPeriod 2: 75% treated with CVVHDF– No influence of CRRT-modality on outcome of patientsNo influence of CRRT-modality on outcome of patients

• Cardiac failure after cardiac surgeryCardiac failure after cardiac surgery– Leading cause of secondary ARF in both decadesLeading cause of secondary ARF in both decades– Increasing mortality rate (neonates !)Increasing mortality rate (neonates !)– Responsible for 46% of non-survivorsResponsible for 46% of non-survivors

• Decreasing number of patients withDecreasing number of patients with– Sepsis, oncologic diseaseSepsis, oncologic disease– No CRRT after burnsNo CRRT after burns

• Young age < 1 year highest mortality rateYoung age < 1 year highest mortality rate– 46% of non-survivors are infants and neonates46% of non-survivors are infants and neonates

20 years of PCRRT in Graz (1985 – 2004)20 years of PCRRT in Graz (1985 – 2004)

• Evaluation with scores (scoring systems)Evaluation with scores (scoring systems)

– Number of organ failuresNumber of organ failures

– Pediatric Risk of Mortality (PRISM-score)Pediatric Risk of Mortality (PRISM-score)

16,8

21,8

12,913,4

12,2

15,5

0,0

5,0

10,0

15,0

20,0

25,0

total survivors non-survivors

1985-1994

1995-2004

†

3,7

4,3

3,23,12,5

3,8

0,0

1,0

2,0

3,0

4,0

5,0

total survivors non-survivors

1985-1994

1995-2004

†††

20 years of PCRRT in Graz (1985 – 2004)20 years of PCRRT in Graz (1985 – 2004)

• Ventilation and vasopressor supportVentilation and vasopressor support– Associated with high mortalityAssociated with high mortality

• Non-resolving MOSF is the leading cause of deathNon-resolving MOSF is the leading cause of death– Period 1: 67% died within 3 to 7 days of CRRTPeriod 1: 67% died within 3 to 7 days of CRRT

– Period 2: 55% died after more than 7 days of CRRTPeriod 2: 55% died after more than 7 days of CRRT

• Our data seem to indicateOur data seem to indicate– Advances in intensive care treatmentAdvances in intensive care treatment

– Advances in diagnosis and treatment of underlying disordersAdvances in diagnosis and treatment of underlying disorders

– High sophisticated CRRT modalitiesHigh sophisticated CRRT modalities

– Leading to slowly decreasing mortality of critically ill childrenLeading to slowly decreasing mortality of critically ill children

– Specific local situations to be consideredSpecific local situations to be considered

Determinants of non-survival after CRRTDeterminants of non-survival after CRRT

• Age (body weight)Age (body weight)– Technical complications decreasingTechnical complications decreasing– Worse survival < 3 kg compared to 3-10 kgWorse survival < 3 kg compared to 3-10 kg

– Symons et al. Am J Kidney Dis 2003; 41:984Symons et al. Am J Kidney Dis 2003; 41:984

• Hemodynamic instabilityHemodynamic instability– Vasopressor supportVasopressor support– Low mean arterial pressure (MAP)Low mean arterial pressure (MAP)

– Smoyer JASN 1995; 6:1401Smoyer JASN 1995; 6:1401

– Bunchman et al. Pediatr Nephrol 2001; 16:1067Bunchman et al. Pediatr Nephrol 2001; 16:1067

• PRISM score:PRISM score: good prognostic capacity good prognostic capacity– Zobel et al. Child Nephrol Urol 1990; 10:14Zobel et al. Child Nephrol Urol 1990; 10:14

– Fernandez et al. Pediatr Nephrol 2005; 20:1473Fernandez et al. Pediatr Nephrol 2005; 20:1473

Determinants of non-survival after CRRTDialytic modality

• Development of 20 years should be of importance

• No systematic review available

• No influence of RRT modality was found– Bunchman et al. Pediatr Nephrol 2001; 16:1067

– Goldstein et al. Kidney Int. 2005; 67:653

• We did a good job even in the early years

• Underlying disorders of importance

Determinants of non-survival after CRRTDeterminants of non-survival after CRRTUnderlying disorderUnderlying disorder

• Cardiac surgery 35% of non-survivors Cardiac surgery 35% of non-survivors (Williams 2002)(Williams 2002)

• Postop. Cardiac surgery 42% of CRRT Postop. Cardiac surgery 42% of CRRT (Fernandez 2005)(Fernandez 2005)

• Left-heart hypoplasia 80% mortality Left-heart hypoplasia 80% mortality (Smoyer 1995)(Smoyer 1995)

• Causes leading to CRRTCauses leading to CRRT• Cardiogenic shock (20%)Cardiogenic shock (20%)• Sepsis (39%)Sepsis (39%)• Organ Tx Organ Tx (Liver, Bone marrow)(Liver, Bone marrow) 22% 22% (Goldstein 2005)(Goldstein 2005)

Determinants of non-survival after CRRTDeterminants of non-survival after CRRTDegree of fluid overload (%FO)Degree of fluid overload (%FO)

• %FO%FO = (Fluid in – Fluid out)/PICU admission weight x 100 = (Fluid in – Fluid out)/PICU admission weight x 100

• Foland et al.,Foland et al., Crit Care Med 2004; 32:1771 Crit Care Med 2004; 32:1771– Survival associated with lower PRISM-score and lower %FOSurvival associated with lower PRISM-score and lower %FO

• Goldstein et al.,Goldstein et al., Kidney Int 2005; 67:653 Kidney Int 2005; 67:653– First report of the Prospective Pediatric CRRT Registry GroupFirst report of the Prospective Pediatric CRRT Registry Group– 116 patients, PRISM higher in non-survivors116 patients, PRISM higher in non-survivors– %FO higher in non-survivors 25.4% vs 14.2% in survivors%FO higher in non-survivors 25.4% vs 14.2% in survivors– Patiens with <20%FO survival 58% vs 40% survival if %FO>20%Patiens with <20%FO survival 58% vs 40% survival if %FO>20%

• %FO may serve as an important parameter for fluid status%FO may serve as an important parameter for fluid status• Guidance of fluid managementGuidance of fluid management• Timing of CRRT (early initiation)Timing of CRRT (early initiation)

ConclusionsConclusions

• 20 years of PCRRT – a story of success20 years of PCRRT – a story of success• Development of high sophisticated equipmentDevelopment of high sophisticated equipment• Changing indicationsChanging indications

– Timing of CRRT in established indicationsTiming of CRRT in established indications

– New indications even without ARFNew indications even without ARF

• Changing diagnosesChanging diagnoses– Decreasing and increasing incidence of diseaseDecreasing and increasing incidence of disease

– „„New“ disorders like BMTNew“ disorders like BMT

• Slowly decreasing mortality ratesSlowly decreasing mortality rates• Prospective Pediatric CRRT Registry Group (Data)Prospective Pediatric CRRT Registry Group (Data)• Intensive care treatment is always on the border-lineIntensive care treatment is always on the border-line