Transcript Document

20 years of PCRRT:
changing indications and diagnoses ?
Ekkehard Ring
Department of Pediatrics
Medical University of Graz
Austria
Historical background of pediatric continuous
renal replacement therapy (PCRRT)
• 1977 Kramer et al. Klin. Wochenschr.
– First report of arteriovenous hemofiltration
(CAVH) in adult patients
• 1986 Ronco et al.
Kidney Int.
– Four critically ill neonates with ARF and
successful CAVH-treatment
• Starting point for intensified development in
PCRRT
In Graz: first CAVH 05/1985
Diabetic coma, rhabdomyolysis
Development of pediatric continuous renal
replacement therapy (PCRRT)
• „Self-made“ arteriovenous devices and circuits
(CAVH), partially with suction support
• Addition of dialysate countercurrent
– Hemodiafiltration (CAVHDF)
Development of pediatric continuous renal
replacement therapy (PCRRT)
• Pump-assisted veno-venous devices
– CVVH, CVVHDF
– Initially leading to hemodynamic instability
– Inaccuracies of blood flow and ultrafiltration
Development of pediatric continuous renal
replacement therapy (PCRRT)
• Improvement of
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Vascular catheters, hemofilters, blood lines
Accuracy of pumps for blood flow and UF
Replacement solutions (bicarbonate)
Anticoagulation (regional, citrate) Minimizing 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 ?
• Questionnaire survey among nephrologists
CRRT PD HD
Belsha 1995 18% 45% 38%
Warady 1999 36% 31% 33%
• „ ...CRRT will soon be used at virtually all
pediatric centers“.
• European Guidelines
– Strazdins et al. Pediatr Nephrol 2004; 19:199
– „choice of dialysis depend upon clinical circumstancies, location of
the patient, and expertise available... Hemofiltration increasingly
employed in the intensive care situation“
Indications for RRT
• Acute renal failure (ARF)
PD, HD, HF available
– Primary renal disorders (isolated ARF)
• Extremely low mortality rate (HUS as most frequent diagnosis)
– ARF as part of multiple organ system failure (MOSF)
• Chronic renal failure (CRF)
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PD, HD, intermittent use of CRRT (HDF) ?
At least 2 of 3 modalities needed in large pediatric clinics
Cost effectiveness of HD-Units in smaller centers
CRRT being established in an open pediatric ICU
HF (HDF) as treatment for CRF to be considered
• A time for rediscovery: chronic hemofiltration for end-stage renal
disease. McCarthy et al. Semin Dial (2003) 16:199
Non-renal indications for CRRT
• Metabolic crisis - inborn errors of metabolism
– Organic acidurias, Urea cycle disorders (hyperammonemia)
– Rapid elimination of toxic metabolites
– Disease specific treatment
• CVVHDF treatment of choice (Highest clearance rates)
– Outcome correlates with rapid elimination rate
» Schäfer et al. NDT 1999; 14:910
– Outcome correlates with coma duration before CRRT
» Picca et al. Pediatr Nephrol 2001; 16:862
• Intoxications with drugs
• Sepsis
– With or without ARF, HF-dosage, removal of mediators ....
Non-renal indications for CRRT
• Liver support in fulminant hepatic failure
– Molecular Adsorbents Recycling System (MARS)
– Promising results
– Open for discussion
• Tissieres et al. Liver support for fulminant hepatic failure: is it time
to use the molecular adsorbents recycling system in children?
Pediatr Crit Care Med 2005; 6:616
• Tumor lysis syndrome
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Significant cause of morbidity and mortality in oncology
Continuous, massive release of intracellular solutes
CRRT is the method of choice
„preventive CRRT“ in high-risk patients
Outcome after CRRT
Change of overall mortality rate ?
• 9 publications (1x 1995), 2000-05 and own data
• Mortality rates 32% - 89% (21 – 226 children)
• 416 / 834 non-survivors = mortality rate 50%
• Data divided by 3 time-periods of patient sampling
No. of patients
Non-survivors
Mortality rate
1985-1994
247
150
61 %
1992-1998
277
138
50 %
1995-2004
310
128
41 %
Long-term surveys of ARF / RRT
Trends in diagnoses and outcome
• Just 1 single-center study
– Williams et al. Arch Pediatr Adolesc Med (2002) 156:893
• Retrospective examination 1979 – 1998
• divided in 2 periods 1979-1988 and 1989-1998
• 228 children with ARF
– Admission to PICU: n = 154 (68%)
• Acute RRT: n = 93 (41%) [60% of PICU admission]
• ARF-mortality rate 27% (no difference between decades)
– Mortality rate of 67% in patients with RRT
Long-term surveys of ARF / RRT
Trends in diagnoses and outcome
• Study of Williams et al. Arch Pediatr Adolesc Med (2002) 156:893
• CRRT starting in the second decade (14% of RRT)
• Unchanged between decades:
– HUS as leading diagnosis with favourable outcome (2% mortality)
– Young age < 1 y represents 57% of non-survivors
• Changes between decades:
– Cardiac surgery main and increasing cause of death (27% >> 44%)
– Decreasing mortality rate in sepsis and burns
– Oncologic complications increasing
• No death with tumor lysis syndrome in the second decade
• Complications with bone marrow transplantation as new disease
20 years of PCRRT in Graz (1985 – 2004)
• Retrospective analysis of 115 consecutive children
• Two periods (1985-1994 and 1995-2004)
1985-1994
1995-2004
Total
Patients
(mortality rate)
87 (45%)
28 (39%)
115 (43%)
Age < 1y
42 (38%)
8 (88%)
50 (46%)
Age 1-6 y
24 (42%)
14 (29%)
38 (37%)
Age 6-18 y
21 (62%)
6 ( 0%)
27 (48%)
• Decreasing incidence of CRRT in the second decade
• Decreasing mortality rate aside from infants
20 years of PCRRT in Graz (1985 – 2004)
• Underlying disorders [No. of patients (mortality rate)]
1985-1994
1995-2004
Total
primary renal
disease
8 (12%)
5 (0%)
13 (8%)
cardiac
surgery
39 (43%)
10 (60%)
49 (47%)
sepsis
14 (43%)
6 (50%)
20 (45%)
oncologic
13 (92%)
2 ( 0%)
15 (50%)
metabolic
7 (14%)
2 (50%)
9 (25%)
burns
3 (0%)
0
3 (0%)
20 years of PCRRT in Graz (1985 – 2004)
• Changes of CRRT technique
– Period 1: 75% treated with CAVH or CVVH
– Period 2: 75% treated with CVVHDF
– No influence of CRRT-modality on outcome of patients
• Cardiac failure after cardiac surgery
– Leading cause of secondary ARF in both decades
– Increasing mortality rate (neonates !)
– Responsible for 46% of non-survivors
• Decreasing number of patients with
– Sepsis, oncologic disease
– No CRRT after burns
• Young age < 1 year highest mortality rate
– 46% of non-survivors are infants and neonates
20 years of PCRRT in Graz (1985 – 2004)
• Evaluation with scores (scoring systems)
5,0
– Number of organ failures
4,0
3,0
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4,3
3,8
3,7
3,1
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3,2
2,5
1985-1994
1995-2004
2,0
1,0
0,0
total
survivors
non-survivors
– Pediatric Risk of Mortality (PRISM-score)
25,0
†
21,8
20,0
16,8
15,0
15,5
13,4
12,9
1985-1994
12,2
1995-2004
10,0
5,0
0,0
total
survivors
non-survivors
20 years of PCRRT in Graz (1985 – 2004)
• Ventilation and vasopressor support
– Associated with high mortality
• Non-resolving MOSF is the leading cause of death
– Period 1: 67% died within 3 to 7 days of CRRT
– Period 2: 55% died after more than 7 days of CRRT
• Our data seem to indicate
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Advances in intensive care treatment
Advances in diagnosis and treatment of underlying disorders
High sophisticated CRRT modalities
Leading to slowly decreasing mortality of critically ill children
Specific local situations to be considered
Determinants of non-survival after CRRT
• Age (body weight)
– Technical complications decreasing
– Worse survival < 3 kg compared to 3-10 kg
– Symons et al. Am J Kidney Dis 2003; 41:984
• Hemodynamic instability
– Vasopressor support
– Low mean arterial pressure (MAP)
– Smoyer JASN 1995; 6:1401
– Bunchman et al. Pediatr Nephrol 2001; 16:1067
• PRISM score: good prognostic capacity
– Zobel et al. Child Nephrol Urol 1990; 10:14
– Fernandez et al. Pediatr Nephrol 2005; 20:1473
Determinants of non-survival after CRRT
Dialytic 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 CRRT
Underlying disorder
• Cardiac surgery 35% of non-survivors (Williams 2002)
• Postop. Cardiac surgery 42% of CRRT (Fernandez 2005)
• Left-heart hypoplasia 80% mortality (Smoyer 1995)
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Causes leading to CRRT
Cardiogenic shock (20%)
Sepsis (39%)
Organ Tx (Liver, Bone marrow) 22%
(Goldstein 2005)
Determinants of non-survival after CRRT
Degree of fluid overload (%FO)
• %FO = (Fluid in – Fluid out)/PICU admission weight x 100
• Foland et al., Crit Care Med 2004; 32:1771
– Survival associated with lower PRISM-score and lower %FO
• Goldstein et al., Kidney Int 2005; 67:653
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First report of the Prospective Pediatric CRRT Registry Group
116 patients, PRISM higher in non-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%
• %FO may serve as an important parameter for fluid status
• Guidance of fluid management
• Timing of CRRT (early initiation)
Conclusions
• 20 years of PCRRT – a story of success
• Development of high sophisticated equipment
• Changing indications
– Timing of CRRT in established indications
– New indications even without ARF
• Changing diagnoses
– Decreasing and increasing incidence of disease
– „New“ disorders like BMT
• Slowly decreasing mortality rates
• Prospective Pediatric CRRT Registry Group (Data)
• Intensive care treatment is always on the border-line