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 1

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

Lowrie (2000) Fleming (1995) Golej (2002) Werner (1996) Santos (2012) Chien (2009) Dittrich (1999) Sorof (1999)

n Time to PD start

17 21 116 23 23 7 27 20 NA 2.5 days (1-6) after surgery NA, but 43% of pts started on PD when CVP>10 mmHg 2.6±0.6 days 4.8±16.8 hrs 1.2±0.4 days after AKI onset In the OR or first hrs in ICU 22 hrs

Pts with negative fluid balance

35% 36% 53% 100% 100% NA 100% 100%

Survivors

24% 38% 47% 53% 56.6% 57% 73% 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

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

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

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)

80 patients (<1 yr)

40 group F 40 group C

Fenoldopam 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 (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 IDO 2 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.

[email protected]

CRRT AND PD IN PEDIATRIC POST-HEART SURGERY AKI: PROS AND CONS

CRRT Fluid removal

Higher

PD

lower

Caloric intake

Higher lower

application anticoagulation

complex easy needed none

CV tolerance

Possibly worst Possibly better

costs

high 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

FO

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

CRRT?

PD?

mortality

AKI

CRRT PD

Time