Transcript Therapeutic Catheterizations - Pediatric Continuous Renal

Risk Factors for Acute Kidney
Injury in Congenital Heart Defects
Ronald G. Grifka, MD
Chief, Cardiology Division
Helen DeVos Children’s Hospital
Professor of Pediatrics
MSU College of Human Medicine
Risk Factors for Acute Kidney
Injury in Congenital Heart Defects
The Elephant…
Risk Factors for Acute Kidney
Injury in Congenital Heart Defects
The Elephant…
Risk Factors for Acute Kidney
Injury in Congenital Heart Defects
What I Will Not Discuss
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Hypertension
FeNa
GFR Calculations
Lupus
Risk Factors for Acute Kidney
Injury in Congenital Heart Defects
Cardiac Hemodynamics
• Normal cardiac index = 3.5 L/min/m2
• Cardiac index = cardiac output/BSA
• For a newborn: 3.2 kg, 0.22 m2
• Cardiac output = 770 ml/min
• If HR = 140/min
• Each heart beat = 5.5 ml
• RBF = 20% of the CO
- RBF = 1.1 ml/heart beat
Risk Factors for Acute Kidney
Injury in Congenital Heart Defects
Cardiac Hemodynamics
• Low cardiac output state: CI = 2.0 L/min/m2
• For a newborn: 3.2 kg, 0.22 m2
• Cardiac output = 440 ml/min
• If HR = 170/min
• Each heart beat = 2.6 ml
• RBF = 20% of the CO
• RBF = 0.52 ml/heart beat
Risk Factors for Acute Kidney
Injury in Congenital Heart Defects
Types of Heart Failure
• Acute vs. Chronic
• New post-op, Myocarditis vs. Dilated CM, DMD, old post-op
• Right ventricle vs. Left ventricle
• TOF, Pulm HTN vs. Anomalous left cor art from PA, DCM
• High output vs. Low output
• Anemia, Hyperthyroid vs. DCM, Myocarditis
• Congenital vs. Acquired
• Mitochondrial disorder, DMD vs. Kawasaki disease, Myocarditis
Risk Factors for Acute Kidney
Injury in Congenital Heart Defects
5 Physiologies of Congenital Heart Defects
• Left to right shunts
• VSD, PDA, AV Canal, ASD
• Right to left shunts
• TOF, Pulmonary atresia
• Transposition physiology
• Obstructive / Regurgitant defects
• AS, PS, CoA, “HLHS”, MS, MR, AI
• Cardiomyopathy
• Dilated, Hypertrophic, Restrictive
Risk Factors for Acute Kidney
Injury in Congenital Heart Defects
Physiology #1 Left to Right Shunt
• VSD, AV Canal, PDA, ASD, Ao-PA Window,
Truncus arteriosus, Single V without PS
• Results in pulmonary overcirculation
• *RARELY causes heart failure (”CHF”), renal
failure
• Tx: Diuretics, ACE inhibitor, ± digoxin
• *Neonates - Truncus Arteriosus, Premie (PDA)
- Intestinal steal  NEC, Renal failure
Risk Factors for Acute Kidney
Injury in Congenital Heart Defects
Physiology #2 Right to Left Shunt
• Tetralogy of Fallot, Pulmonary atresia,
Single ventricle with PS
• Does not cause pulmonary overcirculation!
• Does not cause heart failure (”CHF”)
• Does cause: Cyanosis, Polycythemia, Bleeding
• Partial exchange transfusion if Hct > 62-65%
Risk Factors for Acute Kidney
Injury in Congenital Heart Defects
Physiology #3 Transposition Physiology
• Blue blood to the body, red blood to the lungs
• Not compatible with life as we know it!
• Profoundly cyanotic, hypoxic, acidotic, hypotensive
• Can cause multi-system organ damage if not
treated immediately
• Immediate treatment:
• PDA (PGE1 infusion)
• ASD (Balloon atrial septostomy)
Risk Factors for Acute Kidney
Injury in Congenital Heart Defects
Physiology #4 Obstructive/Regurgitant Defects
• Aortic stenosis/regurge, Pulmonary
stenosis, Coarctation of the aorta,
“HLHS”, Mitral stenosis or regurge
• CAN cause heart failure!
• CAN cause inadequate perfusion to:
• Coronaries (infarction)
• Intestines (NEC)
• Kidneys (ARF)
Risk Factors for Acute Kidney
Injury in Congenital Heart Defects
Physiology #5 Cardiomyopathy
• Dilated, Hypertrophic, Restrictive
• CAN cause heart failure!
• LHF: Inadequate organ perfusion, Pulm edema, SOB, Activity
• RHF: 1° or 2°, Hepato-splenomegally, systemic edema
• DCM: Diuresis, ACE inhibitor, Inotrope, ± Anti-arrhythmic
• HCM:
NO: diuresis or inotrope (unless end stage)
YES: beta blocker, ± Anti-arrhythmic, AICD
• End stage Tx: LVAD (DCM), Heart transplant
Risk Factors for Acute Kidney
Injury in Congenital Heart Defects
Cardiac Related Renal Injury
• Acute insult
• Chronic insult
• An acute insult to a
chronic condition
Risk Factors for Acute Kidney
Injury in Congenital Heart Defects
Cardiac Related Renal Injury - Acute Insult
• Myocarditis
• Acute bacterial endocarditis
• CHD with acute decompensation (URI)
• Aortic stenosis, CoA, DCM
• Catheterization / IV Contrast
• Open heart surgery / CPB
• Heart transplant
• Rejection, meds, infection
• Trauma (hemorrhage, etc)
Risk Factors for Acute Kidney
Injury in Congenital Heart Defects
Cardiac Related Renal Injury - Chronic Insult
• (Systemic) Ventricular failure
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CHD, DCM natural history
Post-op failure
Myocarditis
Transplant: Coronary vasculopathy,
rejection, meds, infection
• Cyanosis
• Repetitive embolic events
• Arrhythmia, thrombotic substrate
Risk Factors for Acute Kidney
Injury in Congenital Heart Defects
Peri-Operative Renal Insults
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Nephrotoxic antibiotics
Furosemide, mannitol  Diuresis, but IVF not replaced
Epi, Norepi, high dose Dopamine  Renal vasoconstriction
Anesthetic agents  Hypotension
Low cardiac output, low blood pressure
Sepsis
Pre-existing renal disease (cyanosis,  Hct, low cardiac output)
Cardiopulmonary bypass
Risk Factors for Acute Kidney
Injury in Congenital Heart Defects
Cardiopulmonary Bypass - Positives
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Allows surgery in a bloodless field
Arrests the heart, decreases MVO2
Perfuses other organs during surgery
Can adjust the blood flow, add medications
Risk Factors for Acute Kidney
Injury in Congenital Heart Defects
Risk Factors for Acute Kidney
Injury in Congenital Heart Defects
Cardiopulmonary Bypass – Negatives
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Fragments RBC’s
Activates platelets
Alters clotting factors
Liberates vasoactive compounds
Hypothermic insult (18-25° C)
Metabolic acidosis
Perfuses organs during surgery with
NON-PULSATILE flow
• P/O transfusions
Risk Factors for Acute Kidney
Injury in Congenital Heart Defects
Peri-Operative Treatment
• Phenoxybenzamine pre-op
• Increase renal blood flow
• Dopamine, fenoldapam, neseritide
• Intra-op, Post-op diuretics
• ± IVF replacement: colloid vs. crystalloid
• Increase BP
• But pressors  SVR,  HR , ?  CO
• Peritoneal dialysis
BenephitTM Infusion System
(FlowMedica, Inc., Fremont, CA)
FDA (510K) Cleared January 2004
Intrarenal infusion
-Dopamine, Fenoldopam
-Nesiritide (BNP)
Risk Factors for Acute Kidney
Injury in Congenital Heart Defects
Cyanotic Heart Disease
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Enlargement of the glomerular capillary tuft
Mesangial hypercellularity
Accumulation of eosinophilic material
Capillary basement membrane thickening
IgM deposits in the mesangium
Fibrin in the glomerular capillary walls
Clinically – GN: hematuria, proteinuria, HTN
Risk Factors for Acute Kidney
Injury in Congenital Heart Defects
Infective Endocarditis
• Kidneys normal to slightly enlarged
• Glomerular immune complex deposition
- C3, IgG. Occasionally IgM, IgA
• Treat SBE, renal function improves
• Advanced SBE disease
• Microabcesses
• Embolization, infarction
• May not recover renal function
Risk Factors for Acute Kidney
Injury in Congenital Heart Defects
Contrast Induced Nephropathy
• Well described entity in adults
• Adults have more pre-existing renal disease, HTN
• Rare in children following cardiac cath
• New contrast much safer
• IVF from anesthesiologist and catheter flushes
• Contrast given over several hour cath procedure
- Up to 12 ml/kg over 7 hr procedure
• Much IV fluids, foley
The Evolution of Contrast Media
Molecular Structure
I
CH3CONH
COO–Na+/Meg+
I
I
R
Era
1950s
R
I
I
R
R
1980s
I
R
I
II
R
R
I
R
COO–Na+/Meg+
I
1980s
I
R
II
I
R
R
R
I
Ionic monomer
Diatrizoate
Iothalamate
Comment
High Osmolality,
5 – 8 blood
Nonionic monomer
Iopamidol
Iohexol
Ioversol
Low Osmolality,
2 – 3 blood,
improved
hydrophilicity
Ionic dimer
Ioxaglate
Low Osmolality,
~2 blood
Nonionic dimer
Iodixanol
(Iotrolan)
Iso-osmolality
Osmolality = blood
R
I
I
Examples
1990s
Osmolality
(mOsm/kg H2O)
Osmolalities of Contrast Media
* 320 mg I/mL
† 350 mg I/mL
‡ 370 mg I/mL
2500
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2000
1500
1000
500
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†
*
0
Iodixanol is a nonionic dimer, formulated with balanced levels of
Ca2+ and Na+, that is isosmolar with plasma at all iodine concentrations
Reduced nephron mass vulnerable to injury
Associated factors: diabetes, poor renal perfusion, others
Contrast enters renal vasculature
Endothelium-independent transient vasodilation (minutes)
Adenosine release from
macula densa
(tubulo-glomerular feedback)
Prostaglandin
dysregulation
Endothelin
release
Decreased Nitric Oxide Synthesis/Release
Sustained intrarenal vasoconstriction (hours)
Prolonged contrast transit time in kidneys
Increased contrast exposure to renal tubular cells
Contrast direct cellular injury and death
Medullary hypoxia
Ischemic injury and death
Catalytic iron-driven oxidative Stress, inflammation, other organ injury processes
McCullough PA, JACC 2008
Acute Kidney Injury
73 y/o with multiple myeloma, Cr 2.3 mg/dl, CrCl=23 ml/min, Cr rise 0.3 mg/dl
Nephrol Dial Transplant
(2004) 19: 1654–1655
One-Year Kaplan-Meier Survival Curves Stratified by CrCl Levels
after Primary Angioplasty in CADILLAC
100
CrCl >60
CrCl 50-60
Survival (%)
90
CrCl 40-50
CrCl 30-40
80
70
CrCl 20-30
60
CrCl <20
50
P<.0001 (all groups)
40
0
50
100 150 200 250 300 350 400 450 500
Time (days)
Sadeghi HM et al. Circulation. 2003;108:2769–
2775.
Calculate eGFR or CrCl
Assess contrast-induced AKI risk
eGFR <30 ml/min
eGFR 30-59 mL/min
Start/continue statin
Discontinue NSAIDs,
other nephrotoxic drugs, metformin
Start/continue statin
Discontinue NSAIDs, other nephrotoxic
drugs, metformin
• Hospital admission
• Other strategies as for
eGFR 30-59 ml
• Nephrology
consultation*
• Consider hemofiltration
pre- and post-procedure
• IV isotonic (NaCl/NaHCO3)
•1.0-1.5 ml/kg/min 3-12 hrs pre and 6-24 post
•Ensure urine flow rate > 150 ml/hr
Discontinue metformin
Good clinical
practice
• Iso-osmolar contrast
•DM, ACS, other added risks
• Low osmolar contrast
•No other added risks
occurs and dialysis is required
N-Acetylcysteine
•< 30 cc diagnostic
•<100 cc diagnostic+intervention
• Consider adjunctive
*Plans should be made in case AKI
† Potentially beneficial agents:
• Limit contrast volume
Serum Cr before
discharge or 24–72 hr
Expectant Care
eGFR ≥60 ml/min
medications†
•Antioxidants
•N-acetylcycteine 1200 mg po bid preand post-procedure
or
•Ascorbic acid 3 g po pre2 g po bid post-procedure
Ascorbic acid
Aminophylline
Prostaglandin E1
None approved for this indication
AKI=acute kidney injury
Cr = creatinine
CrCl=creatinine clearance;
eGFR=estimated glomerular filtration rate
NSAIDs= nonsteroidal anti-inflammatory
drug
IV Hydration and Urine Output
Change in Cr from
Baseline (mg/dL)
r = -0.36, F = 5.73, P = 0.005
Urine Flow Rate (mL/hr), beta = -0.36, t = -3.33, P = 0.001
Baseline CrCI (mL/min), beta = 0.10, t = 0.93, P = 0.36
4.5
3.5
2.5
1.5
0.5
-0.5
-1.5
0
60
120
180
240
Urine Flow Rate (mL/h)
Stevens MA et al. J Am Coll Cardiol. 1999.
300
Regression 95%
CI
Treitl M, et al, Nephrol Dial Transplant (2008)
Hemofiltration
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Hemofiltration works to ensure
– Adequate intravascular volume
– Reduce uremic toxins which may worsen AKI
– Provides stability to the high risk patient after the procedure reducing the
risks of oliguria, volume overload, and electrolyte imbalance that are
associated with short-term mortality.
Double lumen catheter is placed in a jugular or femoral vein for blood withdrawal
and reinfusion and connected to an extracorporeal circuit.
6 hours before contrast: Peristaltic pump (e.g. Prisma hemofiltration pump) at
100 mL/min. Isotonic replacement fluid (post-dilution hemofiltration) 1000 mL/h,
matched with the rate of ultrafiltrate production so no net fluid loss occurs.
5000 IU heparin bolus before initiation followed by a continuous heparin infusion
of 500 to 1000 IU/h through the inflow side of the catheter.
At the time of the cardiac procedure, the hemofiltration treatment should be
stopped, the circuit temporarily filled with a saline solution and short-circuited to
exclude the patient without interruption of the flow.
Immediately after the cath, hemofiltration should be restarted for 12-18 hours.
AKI (Cr >0.5 mg/dL [> 44.2µmol/L])
Dialysis
9 (30%)
3 (10%)
0 (0%)
P=0.002
3 (10%)
0 (0%)
P=0.03
Death
6 (20%)
NS
50
47
42
40
P<0.001
30
%
20
10
3
0
Control
Posthemofiltration
group
Pre/posthemofiltration
group
Marenzi G et al. Am J Med.
2006 Feb;119(2):155-62.
Anatomical Basis: The Coronary Sinus
MCV
69 y.o. with CRI, SCr. 2.9, CTO, 240cc dye
Sensor (Optical Reflectance)
• Delivery fiber shines
visible light into blood
monochromatic,
• Interactions between light and blood cells
results into back-scattering of photons,
which are captured by detection fiber
• Amount of scattered light is proportional
to optical density of blood (i.e. number of
blood cells per volume).
• Signal drop registered when contrast
bolus passes by tip of sensor system
[1] Signal represents contrast presence in coronary sinus
Delivery
Detection
Contrast Detection Signal [1]
In-Vivo Contrast Removal
• Successful device
deployment in CS
• Arterial injection of contrast
• Appropriate size & seal at
CS level
• Contrast recovery: 70%*
Source: CAN-12 CD1_IMG008
* Contrast recovery established by UV Spectrometry
Risk Factors for Acute Kidney
Injury in Congenital Heart Defects
This is not the end.
Nor is it the beginning of the end.
But perhaps, this is the end of the beginning.
Risk Factors for Acute Kidney
Injury in Congenital Heart Defects
Thank you, and looking toward the future in Grand Rapids….
Risk Factors for Acute Kidney
Injury in Congenital Heart Defects
Risk Factors for Acute Kidney
Injury in Congenital Heart Defects
Ronald G. Grifka, MD
Chief, Cardiology Division
Helen DeVos Children’s Hospital
Professor of Pediatrics
MSU College of Human Medicine