AETIOPATHOGENESIS & MANAGEMENT OF ACUTE RENAL FAILURE

PRESENTER Dr Unnikrishnan PCOORDINATOR Dr SugandhaMODERATORS Dr Sheela Rani Dr Suneesh DEPT OF ANESTHESIOLOGY, MCH-TVM

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Human beings are essentially big bags of water, the volume of which must be kept under tight control, to prevent us from either drying out or drowning…..

Highlights…

FOLLOWING THE TRENDS….

CAPTURE THE KEYS TO OPEN THE DOOR

HOW TO PREVENT ARF [Anesthetist Rested during Failure]

NEVER ENDING CONTRAVERSIES

REPLACING KIDNEY […very difficult]

‘ACUTE KIDNEY INJURY’

Abrupt reduction [<48 hrs] in kidney function, defined as an absolute increase in S creatinine of ≥0.3 mg/dLA percentage increase in S creatinine of ≥ 50% [1.5 fold from baseline] or a reduction in urine output-- documented oliguria of < 0.5 ml/kg/hr, for more than six hours.

STAGING SYSTEM FOR A.K.I.STAGE S.CREATININE

CRITERIAURINE OUTPUT CRITERIA

1 INCREASE IN S.CREATININE ≥0.3mg/dL OR INCREASE TO ≥ 150-200% FROM BASELINE

<0.5 ml/kg/hr FOR >6HRS

2 INCREASE IN S.CREATININE TO >200-300%[2-3 FOLD] FROM BASELINE

<0.5 ml/kg/hr FOR >12 HRS

3 INCREASE IN S. CREATININE TO >300%[>3 FOLD] FROM BASELINE OR S.CREATININE OF ≥4mg/dL WITH AN ACUTE INCREASE OF ATLEAST 0.5 mg/dL

<0.3ml/kg/hr FOR 24 HRS OR ANURIA FOR 12 HRS

RIFLE criteria

CLASSIFICATION

AETIOPATHOGENESIS

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PRERENAL ARF

Most common

Renal hypo perfusion

Important form in perioperative period

. CAUSES-PRERENAL ARF

HYPOVOLEMIA>HEMORRHAGE>G-I LOSSES>DECREASED INTAKE>URINARY LOSSES>SKIN LOSSES>OTHERS:BURNS,PANCREATITIS,SEVERE HYPOALBUMINEMIA

ALTERED RENAL HEMODYNAMICS

LOW CARDIAC OUTPUT STATES>CHF >VALVULAR HEART DISEASE >PPV > REDUCED VENOUS RETURN

SYSTEMIC VASODILATION>SEPSIS >ANTIHYPERTENSIVES >VASODILATORS >ANAPHYLAXIS

RENAL VASOCONSTRICTION>CATECHOLAMINES >HYPERCALCEMIA

IMPAIREMENT OF RENAL AUTOREGULATION>NSAIDs >ACE-I >ARBs

HEPATORENAL SYNDROME

HYPOVOLEMIA- extrinsic

HYPOVOLEMIA- intrinsic

Tubuloglomerular feedback

Afferent arteriolar vasodilatation

Preferential efferent arteriolar vasoconstriction

Aim is to utilize the existing filtration reserve

maximally

In short….

EXTRINSIC INCREASE MAP, IMPROVE INTRAVASCULAR VOLUME

INTRINSIC IMPROVE RENAL PLASMA FLOW, GFR & GLOMERULAR PRESSURE

When the insult cross the limits….

Compensatory mechanisms overwhelmed renal perfusion decrease GFR fall

Decreased O2 delivery needs to decrease its work decrease filtration oliguria

Increased Na reabsorption = more work by medulla blood flow towards medulla ,i.e. away from cortex GFR decrease oliguria

“acute renal success” Increase perfusion pressure If we wait …..ATN

Hepatorenal syndrome

Unique form of prerenal ARF

Structurally normal

Profound renal vasoconstriction

Correction of liver disease resolution

INTRINSIC ARFCAUSES

RENOVASCULARRENOVASCULAR>ATHEROEMBOLISM >MALIGNANT HTN > >HUS > DIC >PREECLAMPSIA

GLOMERULARGLOMERULAR>AGN

TUBULESTUBULES-ATN

ISCHEMIAISCHEMIA>MAJOR CARDIOVASCULAR Sx >TRAUMA >HEMORRHAGE >HYPOVOLEMIA

TOXINSTOXINSExogenous: Radiocontrast dye,Antibiotics-Aminoglycosides,Chemotherapeutic agents-Cisplatin, Amphotericin-B, Ethylene glycolEndogenous: myoglobin,hemoglobin,calcium,bilirubinSEPSISSEPSIS

INTERSTITIUMINTERSTITIUMAllergic: Antibiotics : b-lactam ,quinolone , rifampin NSAIDs B/L pyelonephritis

INTRATUBULAR OBSTRUCTIONINTRATUBULAR OBSTRUCTION acyclovir, methotrexate , indinavir , myeloma proteins

Ischemic ATN

4 PHASES

INITIATION:GFR DECREASE , OBSTRUCTION BY DEBRIS , BACKLEAK

EXTENSION : CONTINUED….

MAINTENANCE : GFR LOWEST , URINE O/P LOWEST, UREMIC COMPLICATIONS MAY OCCUR

RECOVERY : EPITHELIAL CELL REGENERATION , GFR RETURNS

The so called diuretic phase…

• Recovery phase• Filtration recovers early• Recovery of epithelial function lags behind

Nephrotoxic ATN

RISK FACTORSRISK FACTORS

Advanced agePreexisting kidney diseaseHypovolemiaCCFMultiple myeloma

Toxins….

Contrast nephropathy

FEATURES

REVERSIBLE

ACUTE ONSET [24-48 HRS]

PEAK 3-5 DAYS

RESOLUTION IN ONE WEEK

B UREA & S CREATININE INCREASE

Atheroembolic ATN

After manipulation of aorta or renal arteries during surgery / angiography / traumaIn patients with atherosclerosisFrequently irreversible

POSTRENAL ARF

Obstruction is always the most likely cause when there is anuriaB/L uretericU/L ureteric if single functioning kidneyBladder neck obstructionUrethral

Perioperative oliguria - pathophysiology

• Anesthetic agents: no renal vasodilation per se ; effects by reducing CO & BP

• EDB & high spinal anesthesia reduce sympathetic tone

• PPV decrease renal blood flow• ACE-I cause significant reduction in perfusion

pressure during anesthesia• Narcotics can increase ADH response

Raised intra abdominal pressure

Normal 0-17mm of Hg>20 mm of Hg compression of pelvis anuria

Improvement occurs only after decompressionMay also cause false high CVP readings due to decreased venous return

SITUATIONS

EMERGENCY LAPAROTAMIES

LEAKING ABD AORTIC ANEURISMS

INTESTINAL DISTENSION

PARALYTIC ILEUS

ASCITES

Clinical features

Pre renal

vomiting , diarrhoea Intestinal obstruction….Carry over cases..NPOOOOOOO

Look forThirstReduced JVPDecreased skin turgorDry mucus membrane

Intrinsic renal

oliguria,edema,hypertension AGNIntake of nephrotoxic drugsh/o atrial fibrillation : renal artery thrombush/o vascular surgeries : atheroembolic ARFMuscle trauma : rhabdomyolysis

Post renal

AnuriaFlank painh/o prostatic disease

INVESTIGATIONS

URINE MICROSCOPY

CONDITION FINDINGS

PRERENAL TRANSPARENT HYALINE CAST

POSTRENAL HYALINE CAST/PUS CELLS/HEMATURIA

ATN MUDDY BROWN GRANULAR/EPITHELIAL CAST

INTERSTITIAL NEPHRITIS WBCs, RBC CASTS, NON-PIGMENTED GRANULAR CAST,EOSINOPHILS, LYMPHOCYTES

AGN RBC CASTS

Assessment of GFR

Blood urea

15-40mg/dL

Increased in dehydration , post G-I bleed

May be a better guide in timing dialysis to avoid uremic complications

Serum creatinineNormal: <1.5 mg/dLOverestimate GFRLags behind renal injury & recoveryRise by 1-2 mg/dL in ARF,>2mg/dL in rhabdomyolysisCritically ill patient: a “normal” value may not be normal

condition creatinine

prerenal fluctuate

ATN Peak by 7-10 days

Contrast nephropathyIschemic ATN

Rise within 24-48hrs, peak in 3-5 days , reach baseline in 7-10 days

AMINOGLYCOSIDE Rise delayed till 2nd week

Creatinine clearance

Volume of plasma cleared off creatinine per unit timeEarlier warnings, 2hr samples[140-age] x body wt / / S.Creatinine x 7291-130 ml / min CrCl = U. Creatinine [mg/dL] x volume [mL/min] P Creatinine[mg/dL]S cystatin C

Assessment of tubular function

• Renal Failure IndicesPRERENAL INTRINSIC

FENa <1 >1

URINARY Na <20 >40

URINE OSM >400 250-300

URINE:PLASMA OSMOLALITY

1.4:1 1:1

Ur.Cr : P. Cr >50:1 <20:1

BUN/Cr >20 <10

SPECIFIC GRAVITY

>1.018 <1.015

Assessment of tubular function

Differentiate pre renal from intrinsic renal failureFeNa is the most usefulRatio of Na clearance to Creatinine clearancePrerenal intact tubules Na reabsorption avidly takes place Cr Cl high FENa <1ATNNa absorption impaired FENa > 1CKD & diuretics also FENa >1Metabolic alkalosis FECl better

Radiology

Abdominal USGSmall Htve Nephrosclerosis , CRFNormal / large DM , AmyloidosisLarge kidneys with large dilated pelvis and uretersPyelography : localizationMRA/ Doppler US : arterial /venous obstruction

Others

renal biopsy Increased potassium ,phosphorus , CK-MM, Uric Acid, decreased Calcium rhabdomyolysis

Complications

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Complications

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Complications

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Also…

hyperphosphatemiaInfectionUremic syndromeHypovolemia due to vigorous diuresis in recovery

Prevention of ARF- in perioperative period

Identify patients at riskPATIENT FACTORS TYPE OF SURGERY

CKD CARDIOPULMONARY BYPASS

ELDERLY AORTIC ANEURYSM SURGERY

NEPHROTOXINS HEPATIC/RENAL TRANSPLANTATION

HYPOVOLEMIA/HYPOTENSION SURGERY IN TRAUMA/BURNS

SEPSIS

HEMORRHAGE

LIVER DISEASE/JAUNDICE

DM,HTN

MULTIPLE MYELOMA

PREECLAMPSIA

MASSIVE BLOOD TRANSFUSION

ATHEROSCLEROTIC DISEASE

CARDIAC DYSFUNCTION

Adequate pre-intra & post op hydration

Large bore cannulaCalculate for deficit correction ,maintenance,3rd space lossesFluid challenge:250-500mL of NS over 10-15 minsIf CVP monitoring established:

small elevation[1-2mm]= need more

large increase[5mm] = be slowColloid Controversies over use

in sepsis

Maintain renal perfusion pressure

• Maintain MAP at 70-100 mm of Hg• Catecholamines may help if there is a cause

for hypotension other than hypovolemia

Hemodynamic &urinary output monitoring

Blood pressureCVPPAWPUrine output ensure catheter is not compressed ensure good urine flow from start monitor output hourly ensure output >1ml/kg/hr

Avoid nephrotoxins• ACE-I & ARB• NSAIDs• AMINOGLYCOSIDES• AMPHOTERICIN-B• CISPLATIN• ASPIRIN• CYCLOSPORIN• LMW-DEXTRAN• ACYCLOVIR,INDINAVIR• METHOTREXATE

Aggressive fluid loading

TraumaCompartment syndromeLimb revascularization

….high chance for rhabdomyolysis

Adequate oxygenation

Pharmacologic strategies

Mannitol

Improve urinary flowPlasma expansionOsmotic hemodilutionFree radical scavengingVolume increase volume depletionIncrease O2 consumptionPulmonary edema, intra renal vasoconstriction

Mannitol

• 6.25-12.5g is given 15 mins prior to the defined insult / repeated 4-6 hrs

• 24 hr cumulative dose not >1.5 mg/kg• Aortic surgeries• Renal transplantation• CABG• rhabdomyolysis

Frusemide

• Inhibit Na-K ATPase in mTAL• Renal vasodilation• Clear debris • oliguric to non oliguric conversion• segmental blockade with thiazide e.g.

metolazone 2.5-5.0mg po• Ototoxicity, interstitial nephritis• Shouldn’t be given if pt is not adequately

fluid loaded

Frusemide

• Pigment nephropathy[ 2-3 times the normal dose with aggressive hydration]

• Contrast nephropathy [with saline]• May reverse medullary hypoxia induced by

toxins• 2-10 mg/kg for converting oliguric to non

oliguric renal failure• Continuous infusion 1-10mg/hr after a LD of

10-20mg

Dopamine

• Non specific DA1+DA2 agonist• “subpressor dopamine has proved

ineffective in clinical trials , may trigger arrhythmias and should not be used as a renoprotective agent in this setting”

• S/E: increased myocardial O2 consumption, decrease hypoxic drive, intestinal ischemia

Others

• Fenoldapam• Nor adrenaline• Dopexamine• CCBs• PGE1• ANP• ADENOSINE• AMINOSTEROIDS

ALSO NOTE…

FORCED ALKALINE DIURESIS IN RHABDOMYOLYSIS

N-ACETYL CYSTINE IN ACETAMINOPHEN INDUCED INJURY

CONTRAST NEPHROPATHYhydration , n-acetyl cystiene , theophylline/aminophyllin, bicarbonate containing IVFs[rather than saline]

Treatment of complications of ARF

Hyperkalemia

• regular insulin 10 u + glucose [50 mL 50% dextrose

• Ca gluconate 105 10 mliv• Inhaled salbutamol 5 mg nebulised• Kayexelate,Na polystyrene sulfonate• NaHCO3 50-100 mEq iv• dialysis

others

• Metabolic acidosis: NaHCO3 to keep its level >15mmol/L or pH >7.2

• Hyperphosphatemia :Ca carbonate, Al(OH)3• Hypocalcemia :Ca gluconate , CaCl2• Nutrition• Anemia• Rx of CHF

Renal replacement therapy

Criteria for initiation of RRT

Anuria Oliguria Pulmonary edemaHyperkalemia >6.5mmol/LSevere acidemia <7.2Uremic encephalopathyUremic pericarditisDrug overdose with dialyzable toxins

Dialysis

dialyser,dialysate,blood delivery systemVascular accessDiffusion technique

heparinized blood and dialysate flows in opp direction through a synthetic membrane down a conc. gradientConvection technique

similar to what happens in glomeruli. Blood passes across a filter which has pores of different sizes so as to filter various molecules

hemodialysis

ADVANTAGESEfficient solute removal in short period of timeLower costmore suitable in severe hyperkalemiamore effective than PD in ARF

hemodialysis

DISADVANTAGESNeed for large bore venous accessNeed for anticoagulationNo removal of cytokinesUnsuitable if hemodynamically unstable

Complications Hypotension: poor tolerance to fluid removal or due to acetate component. Treatment decrease blood flow rate , IVFsHypoxemia : loss of CO2 via dialyzer , bronchospasm ,Treatment:Adr / b-agonist / aminophyllineHemorrhage : 1mg of protamine100iu of heparin Arrhythmias Dialysis disequilibrium syndrome: headache, nausea, delirium, seizures

hemodialysis

• Intermittent HD: 3-4hrs per day,3-4 times per week

• Slow Low Efficiency Dialysis ^-12 hrs per day

Continuous RRT

When intermittent HD failsWhen patient is not tolerating intermittent HD due to hemodynamic instability

Types

Arteriovenous

Venovenous

Venovenous

Continuous venovenous hemodialysis

Continuous venovenous hemofiltration

Continuous venovenous hemodiafiltration

Advantages

.better hemodynamic stabilityLess arryhthmiasImproved nutritional supportBetter pulmonary gas exchangeBetter fluid control

Disadvantages

High risk of bleedingImmobilization prolongedCostlyDifficult vascular accessFilter problems

peritoneal dialysis

Less effective than HDUseful if HD not availableBleeding diathesisImpossible to attain vascular accessHemodynamically unstableNo anticoagulation is needed

disadvantagesImpaired drainage

PeritonitisProtein lossCompromised lung functionAbnormal blood sugar & electrolyte valuesVery slow and ineffective when rapid correction is needed

Peritoneal dialysis

Access via a peritoneal catheter1.5-3L of a dextrose containing solution infusedAllowed to dwell for a short period of time[2-4hrs]Convective + diffusive clearance

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“Recent evidence suggest that more intensive hemodialysis [e.g. daily rather than alternative day intermittent dialysis] may be clinically superior and confers improved survival in ARF , once dialysis is required.”

References Harrisons principles of internal medicine,17th eAcute kidney injury network , akinet.orgPrinciples of critical care,2nd e Farokh Erach UdwadiaAcute renal failure, Dr Rebecca Jacob, IJA 2003;47(5)Anesthesia and coexisting disease,4th eccmtutorials.comPerioperative acute renal failure and its management, Dr D Mallikarjuna [isacon-2007

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