1

TREATMENT STRATEGIES FOR AKI AFTER CPB (FENOLDOPAM, EARLY PD)

STEFANO PICCA and ZACCARIA RICCIDialysis Unit- Dept of Nephrology and Urology

CICU- Dept of Cardiology, “Bambino Gesù” Pediatric Research Hospital

ROMA, Italy

In post- heart surgery AKI, which is (are?) the time window (windows?) suitable for a worthy intervention?

OUTLINE

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

RRT

Nephroprotection?

Modified from Sutton, 2002

Fluids

Drugs

Diuretics

• 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

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 AFTER HEART SURGERY IN CHILDREN: FLUID BALANCE AND SURVIVAL THROUGH THE YEARS

• 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

DA-1 dopaminergic receptor agonist

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

M Ranucci Minerva Anestesiol 2010Z Ricci Interact CardioVasc Thorac Surg 2008

PCCM 2006

LIMITATIONS:• RANDOMIZATION• FENOLDOPAM 0,1 mcg/Kg/min• LATE AKI MARKERS WITH LOW SENSIBILITY AND SPECIFICITY

Fenoldopam in newborn patients undergoing cardiopulmonary bypass: controlled clinical trialRicci Z et al. Interactive CardioVascular and Thoracic Surgery 7 (2008) 1049–1053

80 patients (<1 yr)

40 group F 40 group CFenoldopam 1mcg/kg/min 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 (1)

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)

• 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 (1)

• 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.

CONCLUSIONS (2)

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 CPBPrimary Outcomes:• Decreased NGAL and Cystatin C urine levels• Increased UO and decreased plasma creatinine• Decreased diuretics and vasodilator drugs

Time

AKI

mortalityFO

CRRT?

PD?

PDCRRT

PD IN AKI: LIMITED FLUID REMOVAL AND (LOGICAL) EARLY APPLICATION