AKI and CVVH - Pediatric Continuous Renal Replacement Therapy

Dr Umut Selda Bayrakçı
Yıldırım Beyazıt University, Ankara, Turkey
Acute renal failure is not a “cute” renal
failure Druml W, 2004
 The epidemiologic importance of AKI as a public health
problem is underscored
 because renal function can easily and practically
indefinitely be replaced by modern renal replacement
modalities, AKI presents a rather harmless complication
 Despite the advances in the ability to provide dialysis to
children, the out come of AKI remains surprisingly poor
 MORTALITY in critically ill patients
 53 % in the ATN trial
 44.7 % in the RENAL trial
 Even a small reduction in the renal function
(0.3 mg/dl SCr increase) is a risk factor for
morbidity and mortality in hospitalized
 It is not a problem restricted to the kidneys
 It’s a systemic disease process
AKI exerts a fundamental impact
 On the course of disease
The evolution of associated complications
Independently from the underlying disease
Patients with ARF, die not
(only) with but (also) from AKI;
acute renal failure is not a
“cute” renal failure but a
dangerous condition.
Druml W, Intensive Care Med 2004, Bellomo R, et al. Lancet,2012, Hobson CE et al. Circulation
2009, Coca SG et al. Am J Kidney Dis 2009, Murugan R, Kellum JA. Nat Rev Nephrol 2011
Management of AKI
 Largely supportive
 Aimed preventing of life-threatening fluid or electrolyte
 Avoiding or minimizing further renal injury
 Providing appropriate nutrition to allow recovery from acute
illness and renal dysfunction
 Severe AKI or milder AKI in association with severe fluid
overload or solute imbalance may require renal replacement
therapy (RRT)
 When RRT is indicated
 What is the OPTIMAL RRT modality
When to start?
 Should clinicians wait for
 Frank anuria?
 Unequivocal signs of uremia?
 Fluid overload?
 Should treatment be indicated
 Are there reliable indices helping to choose
RRT timing?
Absolute indications to start RRT
 Uremic complications, for example encephalopathy, pericarditis,
 Serum urea at least 36 mmol/l (100 mg/dl).
 K+ at least 6 mmol/l and/or ECG abnormalities.
 Mg at least 4mmol/l and/or anuria/absent deep tendon reflexes.
 Serum pH 7.15 or less.
 Urine output less than 200 ml/12 h or anuria.
 Diuretic-resistant organ edema (i.e. pulmonary edema) in the
presence of AKI.
Acute Dialysis Quality Initiative (ADQI) workgroup,2001
When to start?
 Not only the presence of AKI but also its severity
should be assessed: pediatric RIFLE (Risk, Injury,
Failure, Loss, End stage)
 Severe AKI and/or rapidly deteriorating kidney
function (towards “F” level) RRT initiation should
be considered.
 Particularly if there was failure to respond to initial
 Critically ill patients with mild to moderate AKI (i.e.
RIFLE category R/I): the most challenging
 Decision should be tailored dynamically
 Sometimes we should consider RRT in earlier stages of
 Severe sepsis
 Reduced renal reserve
 Primary diagnoses associated with high catabolic
(septic shock, major trauma, burn, injury)
 Gastrointestinal bleeding, rhabdomyolysis placing
considerable demand on kidney function
 A positive fluid balance and overt clinical fluid overload
When RRT is indicated?
 30 children
 Children with volume excess of 10% or less
improved survival
 21 children on CRRT
 Mean volume excess 16%
 Mean volume excess 33%
did not survived
 116 children with AKI, CRRT, 13 different center
 Mean volume excess 14%
 Mean volume excess 25%
did not survived
Lane PH et al. Bone Marrow Transplant 1994, Goldstein et al Pediatrics 2001
Goldstein et al. Kidney Int 2005
When RRT is indicated?
 As soon as fluid overload occurs
 unless there is excessive solute load
 Reasonable TRESHOLD for initiation of RRT:
fluid overload of 15%
*BUN levels at initiation of RRT was not associated with survival
(increased in nonsurvivors)
Bunchman TE.Nature Clinical Practice 2008
When to start?
 1847 ICU patients with AKI requiring RRT
 Relationship between biochemical, physiological and comorbid
factors at time of RRT start and ICU mortality
 Independent risk factors for ICU mortality
 Mechanical ventilation
 Oligoanuria
 Serum urea
 Cardiovascular failure
 Failure to correct acidosis and development of more organ
failure within 48 hours of RR
 Survivors tended to have higher creatinine and lower urea
levels at the start of RTT
YH Chou et al. Crit Care
Take home message-1
 RRT should be recommended for AKI in critically ill
patients before organ failure and and metabolic
derangements have reached the slippery threshold
of irreversibility!!
 Creatinine is not an ideal biomarker for decision on RRT timing
 New biomarkers will hopefully improve the performance
of creatinine, urea and RIFLE
The message-2
 The decision when to start RRT should be established
case by case and guided by
 Associated dysfunction of other organ systems
 patients’ AKI severity
 Urine output
 Serum pH
 locally available technics and devices
Stuivenberg Hospital Acute Renal Failure
Project (SHARF)
 RRT patients have higher mortality (43 vs
 Longer ICU and hospital stay compared to
patients treated with conservative
Elseviers MM et al. Crit Care 2010
Which is the best dialysis
The two most important factors that
influence choice of dialysis:
 The indication for dialysis
 Overall clinical status of the patients
*The decision will be based upon
 Specific patient characteristics
 Patients requirements/limitations
 The status of major organ systems
 LOCAL EXPERTISE with specific
dialysis techniques
 Facility experience
 Local resources
Should intermittent RRT or continuous
RRT be used
 No suitable powered randomized controlled trials
 Results of present studies do not suggest a
difference in patient survival
 On the basis of patient survival all seem to be
 State of the art
 Clinical status of the patient
 Intermittent HD requires careful use in patients
with impaired hemodynamic status
 Venovenous forms of CRRT is considered
superior to other forms of CRRT because of
 Lover risk of hemorrhage
 Less frequent circuit clotting
 More predictable driving pressure through
the hemofilter
Advantages of CVVH
1. Continuous solute clearance and ultrafiltration
 Gradual removal provided by hemofiltration
**Ideal modality for patients with cardiovascular instability
and hypotension
 Continuous removal
 Fluid restriction is usually unnecessary
 Freedom to provide large volumes of nutritional support,
drugs, blood products etc..
Advantages of CVVH
2. Specific metabolic advantage
Wide variety of metabolic problems can be corrected easily
Severe metabolic acidosis
Lactic acidosis
Electrolyte abnormalities (s.a. hyperkalemia)
Superior control of uremia than intermittent HD
It can also be adopted to gradually correct hyperosmolar
3. Less likely to lead to cerebral edema
4. Removal of mediators of inflammation
Cost of dialysis equipment (in U.S. dollars)
Manual Automated İntermittent Continious
Ultra Set
Freedom cycler
Cost per unit
Cost of
$24.43/2 L
Pediatric tubing
set $32.00 each
dialysate as at
100HG dialyzer
$50.00 each;
$11.40 each
M60 hemofilter
set (filter and
$160.00 each
Flynn JT, Pediatr Nephrol 2002
1995: 42 children (following repair of congenital heart dis):
 21 PD
21 HF; 9 CAVH, 12 CVVH
Survival: identical
Fluid removal, urea and creatinine clearance, and caloric
intake superior in HF
Fleming et al, J Thoracic Cardiovasc Surg, 1995
Adults: Because of limitations in clearance and difficulties in fluid
removal PD is rarely used in ARF
Pediatrics: PD used to be the first choice; technical difficulties of HD in
infants and young adults
1997: Comparison of HD and hemofiltration in pediatric ARF
 122 children with ARF (retrospective)
 58 HD
 64 HF
 Survival: 83% in HD, 48% in HF group
Higher percentage of children with primary renal dis in HD group
Higher percentage of patients with sepsis in HF group,
greater severity of illness in HF
Maxvold et al; Am J Kid Dis 1997
Comparison of 3 dialysis modality
 279 children with ARF and/or inborn errors of
metabolism (retrospective)
 59 PD
 140 HF
 80 HD
 Overall survival was 53%
 Variation in survival among modalities for certain
Comparison of 3 dialysis modality
 ARF following bone
 ARF following repair of
marrow transplant
congenital heart disease
 %78 intermittent HD
 100% intermittent HD
 33% PD
 33% PD
 21% HF
 50% HF
 Hemodynamic instability
 affect patient outcome
 predictive of modality choice
 patients who were the most hemodynamically unstable were usually
treated with either HF or PD whereas stable patients were usually
treated with intermittent HD.
Bunchman TE, J Am Soc Nephrl, 1999, abstr
 Retrospective
 Single center study designs
 Small patient numbers
 Homogenous patient populations: results
couldn’t be generalized
Intermittent HD vs CRRT
 Multicentre, prospective,
randomized, controlled trial
 Single center, randomized,
controlled trial (CONVINT)
 316 adults, AKI patients
 252 adult AKI patients
 Mortality:
 Survival rate: 39.5% IHD
intermittent HD:62.5%
CRRT: 58.1%
 Modality of RRT has no
impact on the outcome in
43.9% CVVH
 No significant difference
regarding mortality, renal
outcome measures or
Schefold JC et al. Critical Care 2014
Rins RL et al. Nephrol Dial Transplant 2009
Intermittent HD vs CVVH
 Multicenter, randomized and prospective
study (21 center, Hemodiafe Study Group)
 Adults with multiorgan dysfunction syndrome
and AKI
 Rate of survival did not differ between the
intermittent HD and CVVH
Vinsonneau C et al, The Lancet, 2006
Intermittent HD vs CVVH
 ATN and RENAL studies suggest that CVVH might
help with renal recovery
 Meta-analysis studies reveals no difference in long
term dialysis dependency
Ghahramani N et al. Nephrology 2008
Suggested modality choice in pediatric ARF
Goal of dialysis
Intermittent HD (w isolated
Continuous HF or PD
Urea clearance
Intermittent HD or PD
Continuous HF or PD
Treatment of
Either normotensive Intermittent HD
or hypotensive
Correction of
metabolic acidosis
Continuous HF or PD
Treatment of
Either normotensive Any; continuous hemofiltration
Hyperphosphatemia or hypotensive
possibly superior
Flynn JT. Pediatr Nephrol 2002
RRT modality: conclusion
 Few data available
regarding pediatric patients
 Decision: empirical
 Consider:
 Underlying disease
 Severity of illness
 Advantages and
disadvantages of the
various modalities
available locally
 Cost
 Although survival was
somewhat the same/better
in intermittent HD group,
provision of HF most likely
contributed to the survival
of many patients who might
not survived had HF not
Maxvold NJ et al. Am J Kid Dis 1997 (abstr)
 Combination
 CRRT: early correction of hemodynamic
instability as long as multiorgan failure exist
 Classic intermittent HD for long lasting-isolated
Rins RL et al. Nephrol Dial Transplant 2009
Dose of CVVH in AKI
 Expression of how much dialysis should be prescribed in
order to achieve a certain level of blood cleansing
 Dose relies on
 Patient clinical picture (catabolic rate, muscle mass,
presence of pulmonary edema, fever, dysionemia etc.)
 Solute to clear (water, urea, electrolytes, cytokines..)
 The final desired blood level of the target solute
 In CVVH (small solute) clearance is essentially considered
equal to UF rate
Optimal RRT dose in ICU: 2 multicenter clinical trials
Compare normal or less intensive renal support to
intensive therapy
VA/NIH ARF trial network
(ATN) study
 1124 patients
 1500 patients
 25 ml/kg/h CVVHDF
 20 ml/kg/h CVVHDF/
vs 40 ml/kg/h
N England J Med, 2009
thrice weekly IHD vs
35 ml/kg/h/daily IHD
N England J Med, 2009
No benefit in outcomes by increases in intensity of RRT
 Normal dose: 20-30 ml/kg/h for continuous
Ricci Z, Ronco C. Current Opinion Critical Care, 2011
 Overt underdialysis might be harmful in ICU!!
 Be careful about the discrepancy between
prescribed and delivered dose!!!
DOse REsponse Multicenter International
Collaborative Initiative (DoReMi)
 The difference between prescribed and delivered dose
 Relies on therapy downtime (the amount of time the
CRRT does not run in a 24 h period),
 clotting of the circuit,
 Vascular access problems
 Prescription errors
Crit Care 2009
When you prescribe 20-25 ml/kg/h during CRRT significant reduction in
dialysis dose delivery should be considered!
 In practice you may need to over-
prescribe RRT with 25% of safety
Recommendation: 30-35 ml/kg/h?
Kellum JA, Ronco C Nat Rev Nephrol 2010
Ricci Z, Ronco C. Curr Opin in Crit Care, 2011
 Low dose heparin
 10-20 IU/kg bolus
 10-20 IU/kg/h continuous drip (target activated clotting time:
180-200 s or partial tromboplastin time that is double the
normal value)
 Citrate anticoagulation
 No anticoagulation
When to stop?
 No randomized controlled trials addressing this issue
 Observational studies have suggested that urine output
can be used to predict successful cessation of CRRT
 Spontaneous urine output >500 ml/day? (adult)
Uchino S et al. Crit Care Med 2009
Complications of CVVH
 High cost
 Technological complexity
 Specialized nursing staff usually required
 Hypothermia
 Membrane bioincompatibility
 Acid-base imbalance
 Electrolyte imbalance
 Removal of drugs and nutrients
 Volume depletion
Common in both CVVH
and IHD
Long-term outcomes
 Mortality is high
 At least 10% of children who survive AKI have evidence of
 Hyperfiltration
 Hypertension
 Microalbuminuria
Puts them at risk of long term progressive loss of kidney function
 Long term follow-up is important!
Early intervention with ACE inhibitors, angiotensin receptor
blockers or other renoprotective therapies if necessary
Askenazi DJ et al. Kidney Int 2006
Firdevs Çalkanoğlu

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