1
TREATMENT STRATEGIES FOR AKI AFTER CPB
(FENOLDOPAM, EARLY PD)
STEFANO PICCA and ZACCARIA RICCI
Dialysis Unit- Dept of Nephrology and Urology
CICU- Dept of Cardiology,
“Bambino Gesù” Pediatric Research Hospital
ROMA, Italy
OUTLINE
In post- heart surgery AKI, which is (are?) the time window
(windows?) suitable for a worthy intervention?
Peritoneal Dialysis in pediatric post-heart surgery AKI
• Does PD provide inflammation mediators removal?
• Does PD provide suitable fluid removal?
Fenoldopam in pediatric post-heart surgery AKI
• Does Fenoldopam provide “nephroprotection” ?
• What Fenoldopam dosages are required to induce
“nephroprotection”?
TIME WINDOWS FOR AKI MANAGEMENT
Fluids
Drugs
Nephroprotection?
Diuretics
RRT
Modified from Sutton, 2002
•
61 children/2262 CPB heart surgery operations underwent PD (2.7%)
•
Time from end of surgery to PD start: 2 hrs - 15 days (median 24 hrs)
•
48/61 (79%) did not survive
PD AFTER HEART SURGERY IN CHILDREN:
FLUID BALANCE AND SURVIVAL THROUGH THE YEARS
author
n
Time to PD start
Pts with negative
fluid balance
Survivors
Lowrie (2000)
17
NA
35%
24%
Fleming (1995)
21
2.5 days (1-6) after
surgery
36%
38%
Golej (2002)
116
NA, but 43% of pts started
on PD when CVP>10
mmHg
53%
47%
Werner (1996)
23
2.6±0.6 days
100%
53%
Santos (2012)
23
4.8±16.8 hrs
100%
56.6%
Chien (2009)
7
1.2±0.4 days after AKI
onset
NA
57%
Dittrich (1999)
27
In the OR or first hrs in
ICU
100%
73%
Sorof (1999)
20
22 hrs
100%
80%
•
•
•
•
PD in 146 neonates and infants after
surgery
“early” PD: at the end of surgery or day
after surgery
Significant better survival at 30 and 90 days
with early PD
Unfortunately, no fluid overload
measurement
Bojan, Kidney Int, 2012
FENOLDOPAM AND NEPHROPROTECTION: MECHANISM
FENOLDOPAM MESYLATE
Short-acting selective DA1 dopaminergic receptor
agonist
M Ranucci Minerva Anestesiol 2010
Z Ricci Interact CardioVasc Thorac Surg 2008
INDUCES:
• Increased cAMP-PKA
production in renal arteries
smooth muscle:
arterial relaxation and
increased renal blood flow
• Increased cAMP
concentration in tubular
cells and inhibition of Na-H
and Na-K ATPase:
increased natriuresis
• Decreased aldosterone
production:
increased natriuresis
PCCM 2006
Fenoldopam in newborn patients undergoing cardiopulmonary bypass:
controlled clinical trial
Ricci Z et al. Interactive CardioVascular and Thoracic Surgery 7 (2008) 1049–1053
LIMITATIONS:
•RANDOMIZATION
•FENOLDOPAM 0,1 mcg/Kg/min
•LATE AKI MARKERS WITH LOW SENSIBILITY AND SPECIFICITY
RESULTS (1)
40 group F
80 patients
(<1 yr)
Fenoldopam 1mcg/kg/min
40 group C
Placebo
No difference:
• Age
• BW
• Heart defect
• RACHS score and operation duration
• CPB, PAM, mean CPB flow, mean Hb media and
lowest T in CPB
• Inotropic score
RESULTS (2)
No difference between group F and controls in:
• Plasma NGAL and CysC
• plasma creatinine levels and urine output
• pRIFLE 50% in group F and 72% in group P (p = 0.08)
• Inotropic score
• ISVR and IDO2
Significant difference between group F and controls in:
• Furosemide and phentolamine administration in group F (p = 0.0085)
CONCLUSIONS (1)
• In pediatric post-heart surgery AKI, early PD can provide
•
•
better survival than late PD application
This occurs in spite of less performing fluid removal and
consequent worst nutrition management compared with
CRRT
Early fluid overload management and/or the less
negative patient selection are probably the clue issues
to explain this
CONCLUSIONS (2)
• In pediatric open-heart surgery, Fenoldopam at 1
•
•
•
mcg/kg/min during CPB is safe
With this dosage, Fenoldopam is able to prevent the
acute rise of proved urinary AKI markers
Patients treated with Fenoldopam require lower diuretic
and vasodilator dosages than controls
Although high- dose Fenoldopam cannot still be
recommended in all children undergoing heart surgery, it
potentially represents a nephroprotection in these
patients.
stefano.picca@opbg.net
CRRT AND PD IN PEDIATRIC POST-HEART SURGERY AKI:
PROS AND CONS
Fluid
removal
Caloric
intake
application
anticoagulation
CV tolerance
costs
CRRT
Higher
Higher
complex
needed
Possibly worst
high
PD
lower
lower
easy
none
Possibly better
low
No prospective study has evaluated the effect of dialysis modality
on the outcome of children with AKI in the ICU setting.
HIGH DOSE FENOLDOPAM CONTROLLED STUDY: METHODS
INCLUSION CRITERIA:
• Age < 1 yr
• Correction in biventricular
anatomy
• RACHS > 1
• CPB
EXCLUSION CRITERIA
• DHCA
• Pre-surgery high creatinine
levels
Rx:
• High dose fenoldopam (1 mcg/kg/min) during CPB
Primary Outcomes:
• Decreased NGAL and Cystatin C urine levels
• Increased UO and decreased plasma creatinine
• Decreased diuretics and vasodilator drugs
PD IN AKI: LIMITED FLUID REMOVAL
AND (LOGICAL) EARLY APPLICATION
CRRT?
PD?
mortality
FO
AKI
CRRT
PD
Time