Download RENAL PROTECTION IN PEDIATRIC CARDIAC SURGERY

BY
DR/ WASEEM Z. AZIZ
LECTURER OF ANAESTHESIA AND
INTENSIVE CARE
AIN SHAMS UNIVERSITY
MARCH 2009
QUESTIONS
1. The risk of development of acute renal
failure after cardiac surgery is highest in:
• a. Neonates.
• b. Infants.
• c. Children.
• d. Adults.
QUESTIONS
2. Which of the following causes
vasodilation of the cortical vasculature?
a. Mannitol.
c. Both.
b. Furosemide.
d. Neither.
QUESTIONS
3. Clinical settings in which mannitol has definitely been
shown to be effective in preventing the deterioration of
renal function is:
a. During and after cardiopulmonary bypass.
b. During and after aortic cross-clamping.
c. During and after hypovolemic shock.
d. Before the administration of cisplatin.
e. None of the above.
QUESTIONS
4. Which of the following statements is least accurate regarding
acute renal failure?
a. Adults with no underlying renal disease who develop acute renal
failure have a worse prognosis compared with children.
b. Following cardiac surgery, the incidence of acute renal failure is
higher in children than in adults.
c. Children over the age of 2 years with acute renal failure have a much
better outlook with meticulous medical care.
d. Spontaneous recovery from acute renal failure is likely to begin 1–3
weeks after onset.
e. The mortality rate for children with acute renal failure is much higher
than in adults
QUESTIONS
5. Which of the following statements is true regarding
management of suspected acute renal failure?
a. In euvolemic patients, the rapid intravenous administration of
mannitol should result in a urine output greater than 0.5 mL/kg within
1 hour if a prerenal etiology dominates.
b. The vasodilatory and natriuretic properties of furosemide are
beneficial when administered early in the course of acute renal
failure.
c. In euvolemic patients, furosemide in an incremental dose of up to 10
mg/kg may be used.
d. If there is no response to a fluid challenge, low dose dopamine could
be added.
e. All of the above
QUESTIONS
6. In a patient who has just been admitted to the pediatric
intensive care unit with new onset of acute renal failure, which
of the following pathophysiological changes is least likely to
occur?
a. Blood urea nitrogen (BUN) and creatinine will rise at 10 and 0.5
mg/dL/day, respectively.
b. Serum HCO3 decreases by 2 mEq/L/day because of release of
tissue phosphate.
c. Serum K+ increases by 0.3–0.5 mEq/L/day.
d. Hypernatremia is commonly observed.
e. Hypophosphatemia and associated hypocalcemia may develop
rapidly after the onset of acute renal failure
Incidence of postoperative renal
dysfunction
•
Postop. renal failure (more in pediatrics) is associated with mortality
rates of 60–90% (more in adults than pediatrics).
• The incidence of renal impairment varies between 4 and 24%
because there is no rigid definition of renal dysfunction.
• In cardiac surgery
Postoperative ARF
sepsis
↑ ICU stay
↑ length of
hospital stay
↑ GI
bleeding
↑ requiring
infection
RENAL UNIT ANATOMY
RENAL PHYSIOLOGY
• RBF = 20% of resting CO
atherosclerosis
↓ CO
↓ by
α- adrenergic ++
(↓ RBF inspite of
maintain BP)
• Intraglomerular blood pressure =the difference between
the pressures in the efferent and afferent arterioles)
• GFR=100-200ml/min
RENAL PHYSIOLOGY
• GFR autoregulated across wide range of ABP but urine
output is not. ( UOP Linear ↑ with arterial BP.
e.g 100mmHg
200
7 times ↑ in UOP
˂50mmHg
stop of UOP
due to slight rise in GFR but ↑ peritubular vascular pr.
↓ reabsorption of
filterate.
RENAL PHYSIOLOGY
• RBF=20% of CO ≈50 ml/min→
O2 delivery≈50ml/min/100gm tissue
• Distribution is not uniform→≈90% to cortex
• O2 utilization only 10%
of total body utilization
low A-V O2 content
difference in kidney
adequate oxygen reserve
?? Why kidney is highly sensitive to hypoperfusion??
?? Why ARF is frequent complication of hypotension?
PARADOX???
Due to physiological gradient of intra-renal
oxygenation with the renal medulla able to function at
ambient oxygen tensions of 2–3 Kpa
This low oxygen tension results from the high oxygen
requirement for tubular reabsorptive activity of sodium
and chloride.
Although
a high percentage of
the medullary region has a
blood goes to cortex
far smaller blood flow
NEED
only about 18% of total
about 79% of the
delivered oxygen
oxygen delivered to it
(heterogeneity of flow and oxygen requirement)
MEDULLA
Needs strict
control
More susiptable to
hypoxic injury→ ATN
esp in thick ascending
limb (mTAL)
ATN occurs by ↓
40-50% of RBF
Loop diuretics protects
(if any) by ↓o2
dependent
reabsorption of mTAL
→ ↓o2 requirement
MEDIATORS AFFECT MEDULLARY
BLOOD FLOW
Vasodilators
•
•
•
•
•
NO
PGE2
Adenosine
Dopamine
Urodilatin (ANP
analogue)
VASOCONSTRICTORS
• ET
• Angiotensin II
• ADH
Tubulo-glomerular
feedback
• insulin-like growth
factor I
• epidermal growth
factor
• tumour necrosis
factor
PHARMACOLOGICAL CONTROL OF RBF
kidney is largely devoid of β2 receptors
++ α1
so CA
++ renin angiotensin system
So, ischemia→ ++ CA→ renal cortical VC
try to redistribute blood flow to the renal
medulla
THE IMMATURE KIDNEY
Children undergoing heart surgery are more vulnerable to
postoperative renal dysfunction relative to adults
• Normal full term
1-3 y
↓
Full renal fun of
adults
Few weeks→
gain most fun =
Acidification of
urine
At birth: anatomic
growth of 1 million
nephrons
3rd trimester→ urine =
amniotic fluid = 1cup/hr
• Preterm
Depends on conceptional age
Delay to retain normal kidney function
The Problematic Definition of
Acute Kidney injury(AKI)
The Conceptual Definition of Acute Kidney injury
(instead of ARF):
“Sudden loss of renal function resulting in the loss of
the kidneys’ ability to regulate electrolyte and fluid
homeostasis”
The Problematic Definition of
Acute Kidney injury(AKI)
 Pediatric AKI definition: a moving target
 Infants
 Cr
in the first few weeks of life may reflect maternal
values
 Children
 Low
baseline Cr makes 0.2-0.3 changes in Cr
significant
 Varying muscle mass
 Adolescents
 Similar
to adults
The Problematic Definition of
Acute Kidney injury(AKI)
 Over
30 published ARF definitions
 All
based on increased serum creatinine levels
 Despite extensive adult hospitalized patient study over
the past 50 years
 Widely
varying spectrum dependent upon study
aims and hypothesis
 Severe
(ARF requiring dialysis)
 Modest (serum creatinine increase of 0.3 mg/dl)
The Problematic Definition of
Acute Kidney injury(AKI)
• Diagnostic criteria for acute kidney injury
http://ccforum.com/content/11/2/R31
An abrupt (within 48 hours) reduction in kidney function currently defined
as an absolute increase in serum creatinine of more than or equal to 0.3
mg/dl (≥ 26.4 μmol/l), a percentage increase in serum creatinine of more
than or equal to 50% (1.5-fold from baseline), or a reduction in urine output
(documented oliguria of less than 0.5 ml/kg per hour for more than six
hours).
NB: - 2 cr levels within 48hrs.
- adequate hydration
- variation of serum creatinine with modern analyzers is relatively small and therefore
increments of 0.3 mg/dl (25 μmol/l) are unlikely to be due to assay variation
Classification/staging system
for acute kidney injury
RIFLE
MODIFIED
RIFLE classification of AKI
http://ccforum.com/content/11/2/R31
Modified from RIFLE
Stage
Serum creatinine criteria
Urine output criteria
1
Increase in serum creatinine of more than Less than 0.5 ml/kg per
or equal to 0.3 mg/dl (≥ 26.4 μmol/l) or
hour for more than 6
increase to more than or equal to 150%
hours
to 200% (1.5- to 2-fold) from baseline
2
Increase in serum creatinine to more than Less than 0.5 ml/kg per
200% to 300% (> 2- to 3-fold) from
hour for more than 12
baseline
hours
3
Increase in serum creatinine to more than Less than 0.3 ml/kg per
300% (> 3-fold) from baseline (or serum
hour for 24 hours or
creatinine of more than or equal to 4.0
anuria for 12 hours
mg/dl [≥ 354 μmol/l] with an acute
increase of at least 0.5 mg/dl [44 μmol/l])
http://ccforum.com/content/11/2/R31
Difference between two classifications
RIFLE
Modified
AKI
Difference
Up to 1 wk
Within 48hs
Cr changes
Stages
3,4,5
5 stages
Renal
replacement
therapy
Stage 3
only
staging
1→Risk in RIFLE
2,3→Injury and
Failure
No 4,5 as being
chronic
Aetiology of postoperative renal dysfunction
Risk Factors (In General)
PREOPERATIVE
ARTERIOPATHY




Pre-existing renal disease.
IDDM
Age ˃65ys or ˂2ys
Major vascular disease.
INTRAOPERATIVE
1.
Hypovolemia→
neurohormonal effects
Sympathoadrenal
aldosterone
ADH
Angiotensin
glucocortcoids
VC
2. nephrotoxins:→intrarenal VC
→↑ osmotic load
3. Renal ischemia: by concurrent
use of ACEI
4.Inflammation: gut ischemia→
endotoxemia→ cytokines
5.Genetic predisposition:
certain gene deletion
→↑% of inflamm. response.
→↑ IL6, IL10→↑% of renal
dysfunction
this deletion is more
with same congenital heart
disease
The etiology of renal dysfunction in
cardiac surgery
Preoperative
Intraoperative
Postoperative
Lack of renal
reserve
Decreased renal
perfusion
Systemic
inflammation
Renovascular
disease
hypotension
Reduced LV
function
Prerenal azotemia
lack of pulsatile flow
Vasoactive agents
recent diuresis
Vasoactive agents
Hemodynamic instability
NPO status
anesthetic effects
Nephrotoxins
impaired LV function
Embolic events
Volume depletion
ACEI/ARB
CPB-induced inflammation
Sepsis
Nephrotoxins
Nephrotoxins
intravenous contrast
free hemoglobin
other medications
Endotoxemia
Inflammation
More Risk in children
• Immature kidney
• More dependent of renin angiotensin
system for perfusion.
• Risk factors are
as adults +
 Neonatal age group
Cyanotic heart disease
CPB duration
Low CO
Perioperative hypotension
In cyanotic heart disease
1. Still most imp risk factor is low CO.
2. Associated pre existing renal anomalies: eg.





Trisomy 21 (down syn)
Trisomy 18 (Edward syn)
Trisomy 13 (Patau syn)
VATER association
22q11 microdeletion
3. chronically→ cyanotic ht dis → chronic hypoxia
3 stages
ectasia of glomerullar capillaries→benign proteinurea (early sign
5 ys age
of renal dysfunction)
mesangial proliferation with destruction changes of capillary wall
2nd decade
glomerular sclerosis
WHAT TO DO?
EARLY IDENTIFICATION
RENAL INJURY
(MARKERS)
EARLY
PREVENTIVE
MEASUERS
IDENTIFICATION OF RENAL INJURY
Urine volume
Urine specific gravity
Urine osmolality
Renal function tests
available for
clinical use
Serum creatinine and
blood urea nitrogen
Urine/plasma
creatinine ratio
Urine/plasma urea
ratio
Urinary sodium
excretion
Fractional excretion
of sodium
Free water clearance
Creatinine
clearance
Renal blood flow
IDENTIFICATION OF RENAL INJURY
Classic methods
Serum creatinine
• Easy measurement
• Proportional to GFR in steady state (not in acute injury)
• Affected by GFR in addition to tubular secretion,
generation and elimination of creatinine.
• Varies with intravascular volume muscle mass, age, and
sex, and it is affected by muscle trauma, fever, liver
disease, and immobilization.
• 50% of the function of the kidney can be lost without an
increase in sCr.
• Change with age. eg. sCr of 1.5 mg/dL corresponded to
a GFR of approximately 77 mL/min in a 20 year-old
black male, it corresponded to merely 36 mL/min in a 80
year-old white female.
CASE
A 10-day-old male infant weighing 950 g was scheduled for
ligation of patent ductus arteriosus (PDA).
•
He was born at 29 weeks gestation and was intubated
immediately after delivery because of respiratory distress. His
condition improved over the following 4 days. However, on the
fifth day of his life the respiratory distress worsened and a
murmur was heard over his chest. Medical treatment for PDA
was attempted unsuccessfully. His blood pressure was 60/40
mm Hg, heart rate 150 beats/minute. The laboratory data
were as follows: white blood cells (WBCs), 17,000/L;
hemoglobin, 11 g/dL; hematocrit, 34%; urine specific gravity,
1.005; protein 1+; sugar 1+; serum calcium 6.0 mg/dL; blood
glucose 60mg/dl, S creatinine 1.6mg/dl ; and arterial blood
gases: pH, 7.30; PaCO2, 45 mm Hg, PaO2, 60 mm Hg on
FIO2 50%; inspiratory pressure, 30/4 cm H2O; and ventilation
rate, 25 breaths/minute.
• The creatinine levels of term infants at birth are 0.6 to 1.2
mg/dL, but within 1 month fall to levels of 0.1 to 0.2 mg/dL.
Preterm infants have relatively high serum creatinine levels
compared with term infants. They are 0.8 to 1.8 mg/dL at birth
and fall to 0.2 to 0.8 mg/dL in 1 month.
• The normal BUN level is 10 to 20 mg/dL in term infants,
whereas it is 16 to 28 mg/dL in preterm infants.
• In infants weighing 1,000 to 3,300 g, the normal urine-specific
gravity is 1.005 to 1.010. A urine specific gravity of more than
1.020 suggests dehydration.
• Glucosuria 1+ normally presents in 13% of preterm infants
who are less than 34 weeks gestational age because the
preterm infant has a decreased renal tubular reabsorption for
glucose. After 34 weeks of gestational age, glucosuria is
usually associated with hyperglycemia.
• Albumin is normally filtered by the glomerulus and is
completely reabsorbed. However, because of tubular
immaturity, 16% to 21% of preterm infants have proteinuria.
IDENTIFICATION OF RENAL INJURY
Classic methods
Creatinine clearance (ClCr) = (urine Cr × urine volume)/ serum creatinine ≈ GFR
Cockcroft-Gault formula:
CrCl = ([140 - age] X weight)/(72 X Scr)
(multiplied by 0.85 if female sex)
overestimates GFR because tubular secretion of creatinine is ignored
FENa is another measure to assess kidney function
FEs =(Us × V) / Ps
FE =the fractional excretion, s =any substance
GFR
Us =the urinary concentration of the substance
Ps = the plasma concentration, and V =the urine flow rate.
renal failure index (RFI) =
UNa
Ucr/PCr
Both RFI and FENa diff. bet renal and prerenal impairment
Also modified by diuretics
IDENTIFICATION OF RENAL INJURY
BIOMARKERS
• Are urinary kidney-specific proteins.
 Ideally
AKI would have a biomarkers like
myocardial infarction (i.e. troponin-1)
 Currently
no Troponin-I like marker to identify the
site or severity of injury, although various
markers are being evaluated
IDENTIFICATION OF RENAL INJURY
BIOMARKERS
IDENTIFICATION OF RENAL INJURY
BIOMARKERS
URINARY
ENZYMES
NAG
AP
Ϫ GT
α GST
π GST
URINARY LOW
MOLECULAR
PROTEINS
Α1 microglobulin
β2 microglobulin
Cystatin C
NHE 3
NGAL
KIM 1
BIOMARKERS
IDENTIFICATION OF RENAL INJURY
BIOMARKERS
Current status of promising acute kidney injury (AKI) biomarkers in various
clinical situations
IDENTIFICATION OF RENAL INJURY
BIOMARKERS
Example :
Cystatin C
Cysteine proteinase inhibitor.
Not depend on muscle mass, sex, and age
Not affected by inflammation, fever, and extrinsic
substances
 Allow earlier detection of renal impairment than
sCr.
KIDNEY-SPECIFIC PROTEINS AND
CARDIAC SURGERY
all original studies from 1990 to 2005 in which kidney-specific
proteins were measured in patients undergoing cardiac surgery
were reviewed…………..but:
 Mostly are observational studies.
 Small no. of patients.
 Pt population are wide (off- and on-pump surgery, CABG
surgery, valve surgery, and even children with correction of
congenital heart disease).
 The period of studying varied from 1 hour to 40 days after
surgery.
 The conventional measures for detecting kidney injury varied
widely; some used CrCl, others used sCr or UOP.
 No common definition for AKI.
 No long term kidney function followup.
So we need more specific studies
Prevention of renal dysfunction and
renal protection in cardiac surgery
The superior doctor prevents sickness;
The mediocre doctor attends to
impending sickness;
The inferior doctor treats actual
sickness;
Chinese proverb
Strategies of Renal Protection
1. Maintain adequate oxygen delivery—by ensuring adequate cardiac
output, adequate oxygen carrying capacity, and proper haemoglobin
saturation.
2. Suppression of renovascular constriction—by ensuring adequate
volume preload, use of infusions of mannitol, calcium entry block,
and angiotensin converting enzyme inhibitors.
3. Renal vasodilation—by dopaminergic agents, prostaglandins, and
atrial natriuretic peptide.
4. Maintain renal tubular flow—by loop diuretics and mannitol (which
may act to prevent tubular obstruction which can cause cellular
swelling, ischaemia and death).
5. Decrease oxygen demand—by use of loop diuretics and mild
cooling.
6. Attenuate ischaemic reperfusion injury—as a result of the release of
oxygen free radicals and calcium ions.
Prevention of renal dysfunction and
renal protection in cardiac surgery
Prevention of
AKI
Strategies
for renal
protection
• Enhancement of
DO2
• Suppression of
reflex V.C.
• Pharmacological
renal V.D.
• Maintance of
tubular flow
• Decrease VO2
Adequate
hydration
Pharmacological
intervention
• Dopamine
• Dopexamine
• Fenaldopam
• ACEIs & ARBs
• diuretics
•ANP
• N- Acetylcysteine
• Theophylline
• Cardiac
glycosides
• Ca+2 Channel
blockers
• Corticosteroids
• Insulin
• Endothelin
antagonist
•PGs
•NO
CPB
hemodilution
hypothermia
Pulsatile perfusion
Oxygenators
And filters
HYDRATION
• Studies for crystalloids vs colloids (no difference)
• Type: ?? NS, LR,…….Hetastarch,albumin…
• Amount:??controversy
Target CVP of at least 14-16mmHg
Fill till signs of overfill just manifest
o CVP>16mmHg
o Drop in PO2/FO2 ratio
o Bilateral crackles
o S3
o Loss of stroke volume variation
PREVENTION
CPB
Why CPB is risky?
Inflammatory
response during
bypass
Increased vasoconstriction
(due to ↑ ET)
Reduced
blood flow in
capillaries
Endothelial
dysfunction
postbypass
Ischemic reperfusion injury
+ low CO & hypovolemia
Evidence of vascular
obstruction and congestion
up-regulation
of adhesion
molecules,
with
increased
levels of
ET1, which
promotes
adhesion
A reduction in
nitric oxide
production
(which
inhibits
adhesion)
Associated
hypoxia and
hypotension
Inflammation in CPB
STIMULI ( surgical trauma, blood contact with CPB surface, Endotoxemia, Ischemia, Hb)
MEDIATORS
Complement:C3a,C5a
Cytokines:IL1,2,6,8,10,
TNFα
O2 free radicals
Transcription Factor
(NF-κB (nuclear factor kappalight-chain-enhancer of
activated B cells)
Effects
Leucocyte extravasation
Lipid perioxidation
Edema
Cell death
ACUTE KIDNEY INJURY
Adhesion Molecules
E,P,L selectin
Integrin CD8/CD11
Ig superfamily: ICAM,VCAM
Glomerulus from group A anesthetized and heparinized
only.
Well-filled capillaries with clear definition of glomerular
anatomy.
AA afferent arteriole; EA efferent arteriole;
GC glomerular capillaries; PD polar diameter
PATHI ET AL
RENAL MICROCIRCULATION AND CARDIOPULMONARY BYPASS
Ann Thorac Surg1998;65:993–8
Glomerulus from group B (cardiopulmonary
bypass at 28°C, for 30 minutes)
Smaller glomerulus with narrowed
capillaries suggesting diversion of flow
through alternative channels
PATHI ET AL
RENAL MICROCIRCULATION AND CARDIOPULMONARY BYPASS
Ann Thorac Surg1998;65:993–8
Glomerulus from group C (cardiopulmonary
bypass at 28°C, for 120 minutes)
Severe reduction in size of glomerulus with
complete loss of functional unit. These act as
shunts between afferent and efferent arteriolar
systems
PATHI ET AL
RENAL MICROCIRCULATION AND CARDIOPULMONARY BYPASS
Ann Thorac Surg1998;65:993–8
Glomerulus from group D (cardiopulmonary bypass at 28°C,
120 minutes; an 30 minutes of normothermic perfusion at the
end)
Some recovery of anatomy of the functional unit, although
shunting of blood past the nephrons is still evident. Narrowing
of the capillaries and increase in intercapillary spaces suggest
interstitial edema
PATHI ET AL
RENAL MICROCIRCULATION AND CARDIOPULMONARY BYPASS
Ann Thorac Surg1998;65:993–8
CARDIOPULMONARY BYPASS
PROCEDURAL FACTORS
clinically, although there are multiple experimental and clinical studies
suggesting that various procedural aspects of CPB may be detrimental to
the kidney, there is no clear consensus that CPB per se causes renal
failure.
??
PROTECTIVE
+
PROTECTIVE
HEMODILUTION
2 opposing effects
As O2 carrying capacity α HCT
Hemodilution
↓ afterload
↓ viscosity
Hemodilution
↑ CO
↓ O2 transport
↑ bl. flow in
↓RBCs oxygenation
microcirculation at postcapillary
venules
↑ O2 Delivery
the net effect is
↑ O2 delivery
HEMODILUTION
From the figure:
the most suitable Hct
is 28-30%
blood
priming for pediatric
population
Hint H. The pharmacology of
dextran and the physiological
background for the clinical use of
Rheomacrodex and Macrodex. Acta
Anaesth Belg 1968;19:119–138
HYPOTHERMIA
• ↓ metabolic rate
• ↑ intracellular PH
• ?? Controversy about:
 Warm cardioplegia
Warm Ht surgery ( normothermic bypass)
• But studies→ less evidence of protective
effects of hypothermia on kidneys.
PULSATILE PERFUSION
More physiologic
Improve microcirculation
But no evidence that is superior to non
pulsatile perfusion in renal protection.
OXYGENATORS AND FILTERS
o When bubble oxygenators was used → multiple
emboli was found in brain, heart and kidneys →
less with membrane oxygenators and arterial
filters.
o But in pediatric units → only 30% of centers use
filters because large amount of volume required
to prime the filters.
PREVENTION
DRUG THERAPY
basic
Others
ET
antagonists
PGE1
Dopamine
ANP
fenoldopam
dopexamine
ACEI
clonidine
Loop
diuretics
mannitol
CCB
pentoxyifylline
dexamethasone
N-acetylcysteine
A single-chain antibody specific for human
C5 (pexelizumab(
DOPAMINE
 ↓ Activity of Na+/K+ ATPase.
 Renal V.D.(D1 receptors in low dose
0.5-2.5 µg/Kg/min).
 ↑ CO (β1 receptors ˃ 5-10 µg/Kg/min).
 Studies → controversy → ?? Diuretic
→ ++ ↑ CO
DOPEXAMINE
• Sympathomimetic agent.
• Mainly on β2 agonist→
+ve inotropic
+ve chronotopic
??↓ vascular resistance
• In animals (not in human)→DA1 agonist
→↑ renal bl. flow→ diuresis
• But human→ diuresis only by ↑ CO.
LOOP DIURETICS
FUROSEMIDE
• Renal V.D.
• ?? Dose: 0.5mg/kg/min. for 48hrs
• ?? Effective prophylaxis (only pigment
nephropathy)
• High-dose furosemide has been shown to
decrease the duration of oliguria and need
for dialysis in patients with ARF, but has
no effect on mortality.
MANNITOL
• Mech:
Osmotic diuretic.
Renal V.D. by ↑ PG production.
Free radical scavenger→↓ ischemic
reperfusion injury.
• AGAIN?????? Clinical trials failed to prove
evidence
Calcium Channel Blockers
• eg: verapamil, diltiazim
• Mech:↑cytoplasmic Ca+ blocked arteriolar vc
by CCB
ACE I
• Pretreatment with ACEI→↓ the increase of
renal vascular resistance associated with
cross clamping.
• But →?? May ↑ postop. Renal dysfunction
Atrial Natriuretic peptide (ANP)
(Urodilatin)
• ANP produced due to stretch by volume overload
• VD of afferent arterioles.
↑GFR
VC of efferent arterioles.
• Anaritide, a synthetic analogue of ANP, there was
improved mortality in treated patients with oliguria.
• administration of urodilatin (a natriuretic peptide found
in human urine) is beneficial in oliguric patients after
cardiac surgery and significantly reduces mortality and
the need for dialysis.
• In comparison with circulating ANP, urodilatin exerts
greater diuretic properties. Its method of action is
thought to involve both improving renal blood flow and
acting upon the distal collecting system
OTHER POSSIBLE
THEREAPIES
1-ET Antagonist
• ET1→ V.C
• We need either→ ET receptor antagonist
OR→ ET antibodies
2- Prostaglandins E1
Endogenous renal V.D
3-DOPAMINERGIC DRUGS
FENOLDOPAM
• Selective DA1 agonist.
• Introduced mainly as an antihypertensive
agent.
• It ↓ blood pressure in a dose-dependent
manner while preserving RBF and GFR.
• Dose: 0.03-0.05 ng/kg/min
3-FENOLDOPAM
• Mech1: DA1 agonist→VD→↑ RBF.
• No effect on myocardial contractility as
dopamine(no β effect)→ less
arrhythmogenic and no tachycardia.
• Mech2: -- of Na+ transport in the mTAL
region →↓ O2 utilization.
3-FENOLDOPAM
• "When
we looked at the results, there was no
difference between the fenoldopam group and
those treated with standard therapy," says
Landoni (Continuous Improvement in Cardiac
Surgery Program )(CICPS).
End point
Fenoldopam, n
(%)
Dopamine, n (%)
p
Acute renal
17 (42.5)
failure (25%
increase in
serum creatinine
from baseline)
16 (40)
0.9
Renal
replacement
therapy
4 (10)
4 (10)
0.9
Death
4 (10)
3 (7.5)
0.5
Bove T et al Circulation 2005; 111:3230-3235
Continuous Improvement in Cardiac Surgery
Program (CICPS)
concluded that
at high risk patients (eg. CABG)
ARF depends on factors linked to poor cardiac
performance and advanced atherosclerotic vascular
disease
not to vasodilatory effects
so, in pediatric population
need more studies
4-CLONIDINE
• α-adrenergic ( α1 and α2) agoniost.
• Mech:
inhibits ADH production (central α1 effect).
Inhibits reabsorption of Na and H2O
( peripheral α2 effect).
block adrenergic VC stimuli to surgical stress
→↓ renal hypoperfusion.
• Dose: 4µg/kg
5-PENTOXIFYLLINE
o PDE Inhibitor→-- activation of neutrophil by
TNFα and IL-1, and TNF-α release by
inflammatory cells.
o No direct effect on kidneys.
6-STEROIDS
(DEXAMETHASONE)
o failed to protect against renal dysfunction after
cardiac surgery.
o A recent study examined the effect of blocking
complement activation in patients who
underwent CPB
7- A single-chain antibody specific for
human C5 (pexelizumab)
C5 → block complement activation→
??renal function after CPB
8- N-acetylcysteine (N-AC)
o block inflammation and oxidant stress in cardiac
surgery patients.
o studied most extensively in the prevention of
radiocontrast induced nephropathy.
SUMMARY
• Renal failure is relative rare complication but
associated with a 10-fold increase in surgical
mortality.
• Although CPB is a nonphysiologic state that alters
renal blood flow and many neuroendocrine
responses affecting the kidney, there is little clearcut evidence that CPB per se is responsible for
renal dysfunction.
• Risk factors mainly:→perop→renal dysfunc
→intraop→infammatory response
→postop→↓ COP
• Protection mainly to maximize postop. COP to
avoid renal hypoperfusion.
Assess hydration and circulation volume.
Principles of management of
oliguria and acute renal failure
Clinical examination
Urinary bladder palpable?
Measure UOP accurately
Biochemistry
Place a urinary cath.
Urinary and plasma electrolytes, urea, creatinine and osmolarity.
Calculate FENa
Nephrotoxins
Calculate U: P ratios for Na+, urea and osmolarity.
Withholding potentially toxic drugs (eg vancomycin, aminoglycosides,...)
Myoglobin(hyperpyrexia)
Hemoglobin(hemolysis)
Circulation
Initiate specific therapy if appropriate
Normalize circulating volume and cardiac output
Renal ultrasound
Optimize treatment of heart failure.
Pattern of renal arterial and venous blood flow (renal artery or vein thrombosis)
Appearance of kidneys.
Fluid management
Rule out potential obstruction.
Initially restrict fluid intake to 30% of normal requirement + UOP
Metabolic management
Renal replacement therapy may be necessary if therapeutic or metabolic demand can not be met within
these fluids limits.
Frequent measurements of plasma biochemistry
Danger of hyperkalemia
Drug therapies to decrease injuries
and promote recovery
Renal replacement therapy
Rapid rise of urea/creatinine may determine early use of renal replacement therapy
Furosemide
Mannitol
Hyperkalemic management
Peritoneal dialysis
Hemofilteration
Hemodialysis
SPECIAL SITUATION
AORTIC SURGERY
•
•
•
Paraplegia and renal failure are the main determinants in postoperative mortalities.
In pediatrics eg. Coarctation, aneurysm (Marfan,..)......
Problem: Aortic cross clamp (suprarenal vs infrarenal)
•
renal protection including:
 Hypothermic CPB with circulatory arrest.
 Selective volume and pressure controlled perfusion by: Retrograde aortic
perfusion,followed by
o
o
o
o
o
warm blood visceral perfusion,
Cold crystalloids renal arteries perfusion
antegrade cold blood visceral perfusion,
retrograde cold blood perfusion, and
the perioperative use of a renal protective pharmacologic agent, fenoldopam.
Perform selective perfusion by 4 branched tubing system connected to extracorporeal
circulation with the 4 braches connected to celiac, superior mesenteric and 2 renal arteries.
 Shunts
o both temporary and permanent .
o These included
 permanent axillo-bifemoral graft ,
 aorto iliac Gott shunt , axillo-femoral Gott shunt ,
 temporary axillofemoral graft ,
 combination of double clamping then temporary perfusion using a Javid
shunt.
o These techniques have the disadvantages of complexity or of incurring
significant period of renal ischaemia.
ASWERS
1. The risk of development of acute renal
failure after cardiac surgery is highest in:
• a. Neonates.
• b. Infants.
• c. Children.
• d. Adults.
1.
A
Kidneys are able to maintain renal blood flow over a wide
range of systemic blood pressures by autoregulation of
intrarenal vascular resistance. Therefore, hypotension with
renal hypoperfusion may or may not produce ischemic renal
injury. However, these autoregulatory mechanisms are not
well developed in neonates. Neonates have high renin
levels, which in turn, are associated with decreased
glomerular filtration rate (GFR) and reduced outer cortical
blood flow. The cortical glomeruli are immature and so are
their corresponding tubules. This pattern of high renin and
reduced outer cortical blood flow makes neonates more
vulnerable to renal dysfunction as a result of hypotension of
systemic pressures only slightly below the normal range. In
animal studies, newborn animals have decreased production
of atrial natriuretic peptide in response to saline challenge.
All these factors combined make the incidence of acute
renal failure in neonates, after cardiac surgery, higher than
in older infants and children. (Nichols DG, et al. Critical
Heart Disease in Infants and Children, Mosby 1995; pp. 125,
562.)
2. Which of the following causes
vasodilation of the cortical vasculature?
a. Mannitol.
c. Both.
b. Furosemide.
d. Neither.
2. C
Furosemide causes vasodilation of the cortical vasculature by
direct action and through release of prostaglandins.
Furosemide maintains renal blood flow and tubular blood flow
when cardiac output is compromised. Mannitol is also a
vasodilator of the cortical vasculature that increases renal
blood flow either directly by drawing fluid from extravascular
to intravascular space, thus increasing total plasma volume,
or by increasing prostaglandin production. Increased plasma
volume alone does not fully explain the effects of mannitol,
because volume expansion with saline improves renal blood
flow without improving GFR. The improvement in GFR seen
with mannitol is associated with a decrease in afferent and
efferent arteriolar resistance, which is probably mediated by
prostaglandins. (Rogers MC, et al. Textbook of Pediatric
Intensive Care, 2nd Edition; pp. 1192–1194, 1202.)
3. Clinical settings in which mannitol has
definitely been shown to be effective in
preventing the deterioration of renal function
is:
a. During and after cardiopulmonary bypass.
b. During and after aortic cross-clamping.
c. During and after hypovolemic shock.
d. Before the administration of cisplatin.
e. None of the above.
3. D
Clinical studies comparing prophylactic
administration of mannitol (or furosemide) with
maintenance of adequate intravascular volume
during cardiopulmonary bypass failed to reduce
the incidence of postoperative renal dysfunction.
However, there are experimental studies that have
shown some beneficial effects of mannitol.
Mannitol has been shown to be effective in
preventing deterioration of renal function before
administration of Amphotericin B and CisPlatinum. (Rogers MC, et al. Textbook of Pediatric
Intensive Care, 2nd Edition; pp. 1194,1195;
Nichols DG. Critical Heart Disease in Infants and
Children, Mosby 1995; pp. 129,130; Olivero JJ, et
al. Br Med J, 1975; 1:550; Hayes D, et al. Cancer,
1977; 39:1372.)
4. Which of the following statements is least accurate
regarding acute renal failure?
a. Adults with no underlying renal disease who develop acute
renal failure have a worse prognosis compared with children.
b. Following cardiac surgery, the incidence of acute renal failure
is higher in children than in adults.
c. Children over the age of 2 years with acute renal failure have
a much better outlook with meticulous medical care.
d. Spontaneous recovery from acute renal failure is likely to
begin 1–3 weeks after onset.
e. The mortality rate for children with acute renal failure is much
higher than in adults
4. E
Children have a lower mortality compared
with adults. (Rogers MC, et al. Textbook of
Pediatric Intensive Care, 2nd Edition; pp.
1198–1201.)
5. Which of the following statements is true
regarding management of suspected acute renal
failure?
a. In euvolemic patients, the rapid intravenous
administration of mannitol should result in a urine
output greater than 0.5 mL/kg within 1 hour if a
prerenal etiology dominates.
b. The vasodilatory and natriuretic properties of
furosemide are beneficial when administered early in
the course of acute renal failure.
c. In euvolemic patients, furosemide in an incremental
dose of up to 10 mg/kg may be used.
d. If there is no response to a fluid challenge, low dose
dopamine could be added.
e. All of the above
6. In a patient who has just been admitted to the
pediatric intensive care unit with new onset of
acute renal failure, which of the following
pathophysiological changes is least likely to
occur?
a. Blood urea nitrogen (BUN) and creatinine will rise
at 10 and 0.5 mg/dL/day, respectively.
b. Serum HCO3 decreases by 2 mEq/L/day because
of release of tissue phosphate.
c. Serum K+ increases by 0.3–0.5 mEq/L/day.
d. Hypernatremia is commonly observed.
e. Hypophosphatemia and associated hypocalcemia
may develop rapidly after the onset of acute renal
failure
5-6. E, D
All of the strategies mentioned are appropriate
for oliguria in a setting of suspected renal
insufficiency. With the onset of acute renal
failure, hyponatremia is more commonly seen
owing to the dilutional effect of intake of fluid
orally, which is mostly hypotonic. (Rogers
MC, et al. Textbook of Pediatric Intensive
Care, 2nd Edition; p. 1202. Nichols DG.
Critical Heart Disease in Infants and Children,
Mosby 1995; pp. 128–138.)