RENAL PRESERVATIONRENAL PRESERVATION

ARF AND ITS ARF AND ITS MANAGEMENTMANAGEMENT

Dr.P.Narasimha Reddy Dr.P.Narasimha Reddy M.D.,D.A.M.D.,D.A.

Professor and HOD Professor and HOD

Department of Department of AnaesthesiologyAnaesthesiology

Kurnool Medical CollegeKurnool Medical College

Kurnool - A.P.Kurnool - A.P.

DEFINITIONDEFINITION ARF IS DEFINED AS A SUDDEN DECREASE IN RENAL ARF IS DEFINED AS A SUDDEN DECREASE IN RENAL FUNCTION THAT RESULTS IN INABILITY OF THE KIDNEY FUNCTION THAT RESULTS IN INABILITY OF THE KIDNEY TO EXCRETE NITROGEN AND OTHER WASTES. TO EXCRETE NITROGEN AND OTHER WASTES.

THIS IS ASSOCIATED WITH PROLONGED HOSPITAL THIS IS ASSOCIATED WITH PROLONGED HOSPITAL STAY AND MORTALITY (58%)STAY AND MORTALITY (58%)

ARF IN SURGICAL PATIENTS INVARIABLY CAUSED BY ARF IN SURGICAL PATIENTS INVARIABLY CAUSED BY ISCHAEMIC INSULT.ISCHAEMIC INSULT.

ATN IS THE MOST COMMON MECHANISM OF RENAL ATN IS THE MOST COMMON MECHANISM OF RENAL FAILURE.FAILURE.

SCENARIO IS HIGH RISK SURGICAL PATIENTS WITH SCENARIO IS HIGH RISK SURGICAL PATIENTS WITH EXPOSURE TO ONE OR MORE NEPHROTOXIC DRUGS.SEXPOSURE TO ONE OR MORE NEPHROTOXIC DRUGS.S

BASIC CONCEPTS OF ANATOMY BASIC CONCEPTS OF ANATOMY AND PHYSIOLOGY OF KIDNEY AND PHYSIOLOGY OF KIDNEY

CONTAINS OVER ONE MILLION NEPHRONS,MAJORITY CONTAINS OVER ONE MILLION NEPHRONS,MAJORITY ARE IN OUTER CORTEX ABOUT 15% IN JUXTA- MEDULLARY ARE IN OUTER CORTEX ABOUT 15% IN JUXTA- MEDULLARY REGION. JUXTA GLOMERULAR APPARATUS - DISTAL CONVULUTED REGION. JUXTA GLOMERULAR APPARATUS - DISTAL CONVULUTED TUBULES PASS IN BETWEEN AFFERENT AND EFFERENT TUBULES PASS IN BETWEEN AFFERENT AND EFFERENT

ARTERIOLESARTERIOLES MACULA DENSA - TUBULAR EPITHELIAL CELLS AND MACULA DENSA - TUBULAR EPITHELIAL CELLS AND SUBSET OF AFFERENT ARTERIOLAR EPITHELIAL CELLS.SUBSET OF AFFERENT ARTERIOLAR EPITHELIAL CELLS.

CONTAINS 8 - 10 LOBES.CONTAINS 8 - 10 LOBES.

BLOOD FLOW: 20% OF COP (OR) 1 LITRE /MIN.BLOOD FLOW: 20% OF COP (OR) 1 LITRE /MIN. KIDNEY KIDNEY WEIGHS ONLY 0.5% OF BODY WEIGHT.WEIGHS ONLY 0.5% OF BODY WEIGHT.

ARTERIO VENOUS OXYGEN DIFFERENCE 1.7 ml/dl 5ml/dl ARTERIO VENOUS OXYGEN DIFFERENCE 1.7 ml/dl 5ml/dl

body).body). EACH KIDNEY WEIGHS 150 grams.BLOOD FLOW 75 TO EACH KIDNEY WEIGHS 150 grams.BLOOD FLOW 75 TO

80%80% GOES TO CORTEX REMAINING GOES TOGOES TO CORTEX REMAINING GOES TO MEDULLA.MEDULLA.

PATIENT FACTORSPATIENT FACTORS

PRE-OPERATIVE RENAL DYSFUNCTIONPRE-OPERATIVE RENAL DYSFUNCTION PERIOPERATIVE CARDIAC DYSFUNCTION PERIOPERATIVE CARDIAC DYSFUNCTION SEPSISSEPSIS HEPATIC FAILURE, OBSTRUCTIVE HEPATIC FAILURE, OBSTRUCTIVE JAUNDICE, ASCITESJAUNDICE, ASCITES

HYPOVOLEMIAHYPOVOLEMIA ADVANCED AGE?ADVANCED AGE? MAJOR OPERATIONSMAJOR OPERATIONS

HIGH RISK SURGICAL PROCEDURES TRAUMA AND BURN SURGERYTRAUMA AND BURN SURGERY: HIGH RISK, HYPOVOLEMIC : HIGH RISK, HYPOVOLEMIC

SHOCK, PIGMENTURIA,EXO-NEPHROTOXINS OR SEPSIS. EARLY SHOCK, PIGMENTURIA,EXO-NEPHROTOXINS OR SEPSIS. EARLY OLIGURIC FORM MORTALITY-90%OLIGURIC FORM MORTALITY-90%

CARDIAC SURGERY (CABG):CARDIAC SURGERY (CABG): MORTALITY-50%, PRESSURE AND MORTALITY-50%, PRESSURE AND TYPE OF BYPASS ARE LESS SIGNIFICANT DURATION AND TYPE OF BYPASS ARE LESS SIGNIFICANT DURATION AND HEMODYNAMIC INSTABILITY ARE IMPORTANT. HEMODYNAMIC INSTABILITY ARE IMPORTANT.

VASCULAR SURGERYVASCULAR SURGERY: AORTIC CROSS CLAMPING HAS BAD : AORTIC CROSS CLAMPING HAS BAD EFFECTS REGARDLESS OF LEVEL OF CLAMPING. SUPRARENAL-EFFECTS REGARDLESS OF LEVEL OF CLAMPING. SUPRARENAL-ATN LIKE LESION, INFRA RENAL-SHORT TIME REDUCTION IN ATN LIKE LESION, INFRA RENAL-SHORT TIME REDUCTION IN GFR, GFR,

AORTIC SURGERYAORTIC SURGERY: ARF IS 25%: ARF IS 25% END STAGE LIVER DISEASES AND CHOLESTASISEND STAGE LIVER DISEASES AND CHOLESTASIS: HIGH : HIGH

INCIDENCE OF ARF (2/3 OF LIVER TRANSPLANTS. MOST OF INCIDENCE OF ARF (2/3 OF LIVER TRANSPLANTS. MOST OF THE TRANSPLANT PATIENTS HAVE OVERT HEPATO RENAL THE TRANSPLANT PATIENTS HAVE OVERT HEPATO RENAL SYNDROME OR ASYMPTOMATIC RENAL DYSFUNCTION OR SYNDROME OR ASYMPTOMATIC RENAL DYSFUNCTION OR VASOSPASM, SUCH PTS IF EXPOSED TO MASSIVE BLOOD VASOSPASM, SUCH PTS IF EXPOSED TO MASSIVE BLOOD TRANSFUSION HEMODYNAMIC INSTABILITY OR NEPHROTOXINS TRANSFUSION HEMODYNAMIC INSTABILITY OR NEPHROTOXINS THE RISK INCREASESTHE RISK INCREASES . .

NEPHROTOXINS

EXOGENOUS:EXOGENOUS: ANTIBIOTICSANTIBIOTICS:AMINOGLYCOSIDES,CEPHALOSPORINS, :AMINOGLYCOSIDES,CEPHALOSPORINS, AMPHOTERICIN B, SULPHONAMIDES, AMPHOTERICIN B, SULPHONAMIDES, TETRACYCLINS, VANCOMYCIN. TETRACYCLINS, VANCOMYCIN.

ANAESTHETICS:ANAESTHETICS: METHOXYFLURANE, ENFLURANE. METHOXYFLURANE, ENFLURANE. NSAIDSNSAIDS: ASPIRIN, IBUPROFEN, DICLOFENAC, : ASPIRIN, IBUPROFEN, DICLOFENAC, KETOROLAC,INDOMETHACIN.KETOROLAC,INDOMETHACIN.

CHEMOTHERAPEUTIC/IMMUNOSUPPRESIVE AGENTSCHEMOTHERAPEUTIC/IMMUNOSUPPRESIVE AGENTS: : CISPLATIN, CYCLOSPORIN, METHOTREXATE, CISPLATIN, CYCLOSPORIN, METHOTREXATE, MITOMYCIN, NITROUREAS, TACROLINIUM.MITOMYCIN, NITROUREAS, TACROLINIUM.

CONTRAST MEDIACONTRAST MEDIA . .

NEPHROTOXINSNEPHROTOXINS

ENDOGENOUS:ENDOGENOUS: HYPERCALCEMIAHYPERCALCEMIA HYPERURICEMIAHYPERURICEMIA HYPERURICOSURIAHYPERURICOSURIA RHABDOMYOLYSISRHABDOMYOLYSIS HAEMOLYSISHAEMOLYSIS BILIRUBINBILIRUBIN OXALATESOXALATES PARAPROTIENSPARAPROTIENS

PRE OP OPTIMIZATION:PRE OP OPTIMIZATION:

1) EARLY IDENTIFICATION OF THE PROBLEM : INTRAVASCULAR VOLUME 1) EARLY IDENTIFICATION OF THE PROBLEM : INTRAVASCULAR VOLUME STATUS-MAINTAINANCE OF EFFECTIVE INTRAVASCULAR VOLUME, I.V. STATUS-MAINTAINANCE OF EFFECTIVE INTRAVASCULAR VOLUME, I.V. FLUIDS MAY BE STARTED ONE DAY BEFORE SURGERY, HEMODYNAMIC FLUIDS MAY BE STARTED ONE DAY BEFORE SURGERY, HEMODYNAMIC MONITORING-- CVP, PA AND WEDGE PRESSURES, CI, SVR ARE HELPFUL MONITORING-- CVP, PA AND WEDGE PRESSURES, CI, SVR ARE HELPFUL IN OPTIMIZING THE FLUID VOLUME. CONTINOUS BP MONITORING AND IN OPTIMIZING THE FLUID VOLUME. CONTINOUS BP MONITORING AND MAINTAINING IT IN NORMAL RANGE. URINARY CATHETERIZATION MAINTAINING IT IN NORMAL RANGE. URINARY CATHETERIZATION (URINARY OUT PUT IS A POOR MONITOR OF KIDNEY FUNCTION).(URINARY OUT PUT IS A POOR MONITOR OF KIDNEY FUNCTION).

2) ASSOCIATED MEDICAL, SURGICAL AND NEPHROTOXIC EXPOSURES: 2) ASSOCIATED MEDICAL, SURGICAL AND NEPHROTOXIC EXPOSURES: ASSOCIATED MEDICAL CONDITIONS TO BE ATTENDED, TIME OF SURGERY ASSOCIATED MEDICAL CONDITIONS TO BE ATTENDED, TIME OF SURGERY IS MINIMIZED, SPACING OF PROCEDURES AND AVOIDING NEPHROTOXIC IS MINIMIZED, SPACING OF PROCEDURES AND AVOIDING NEPHROTOXIC AGENTS.AGENTS.

3) ANAESTHETIC PLAN THAT EMPHASISES RENAL PRESERVATION . 3) ANAESTHETIC PLAN THAT EMPHASISES RENAL PRESERVATION .

STRATEGIES TO PREVENT P.O. ARF

PHARMACOLOGICAL STRATEGIES IN THE PAST IT WAS AIMED AT INCREASING GFR, IN THE PAST IT WAS AIMED AT INCREASING GFR, PROMOTION OF TUBULAR FLOW AND REMOVAL OF PROMOTION OF TUBULAR FLOW AND REMOVAL OF TUBULAR DEBRIS.TUBULAR DEBRIS.

RECENTLY IT HAS BECOME APPARENT THAT RECENTLY IT HAS BECOME APPARENT THAT MAINTAINANCE PHASE OF RENAL DYSFUNCTION IS MAINTAINANCE PHASE OF RENAL DYSFUNCTION IS PERPETUATED BY SEVERAL MECHANISMS THAT CAUSE PERPETUATED BY SEVERAL MECHANISMS THAT CAUSE CELLULAR INJURY.CELLULAR INJURY.

CURRENT CONCEPT IN RENAL INJURY IS CURRENT CONCEPT IN RENAL INJURY IS “CELLULAR “CELLULAR INJURY PARADIGM”.INJURY PARADIGM”.

SOME PHARMACOLOGICAL RENAL PRESERVATIVE AGENTS SOME PHARMACOLOGICAL RENAL PRESERVATIVE AGENTS WILL ACT AT BOTH HEMODYNAMIC, HYDRAULIC LEVEL WILL ACT AT BOTH HEMODYNAMIC, HYDRAULIC LEVEL AND AT THE CELLULAR OR EVEN SUB CELLULAR AND AT THE CELLULAR OR EVEN SUB CELLULAR LEVEL.LEVEL.

THEY INCREASE BLOOD FLOW BY INHIBITING VOLTAGE DEPENDENT THEY INCREASE BLOOD FLOW BY INHIBITING VOLTAGE DEPENDENT CALCIUM CHANNEL MEDIATED VASOCONSTRICTION, HYPERTENSIVE CALCIUM CHANNEL MEDIATED VASOCONSTRICTION, HYPERTENSIVE PATIENTS TREATED WITH CCB- SLOW DECREASE IN SR.CR. PATIENTS TREATED WITH CCB- SLOW DECREASE IN SR.CR. CLEARANCE.CLEARANCE.

IN TRANSPLANT PATIENTS THEY SHOWED MIXED RESULTS, TREATED IN TRANSPLANT PATIENTS THEY SHOWED MIXED RESULTS, TREATED WITH DILTEAZEM SHOWED INCREASED RBF, GFR AND URINEOUTPUT WITH DILTEAZEM SHOWED INCREASED RBF, GFR AND URINEOUTPUT AND DECREASED REQUIREMENT OF DIALYSIS.AND DECREASED REQUIREMENT OF DIALYSIS.

IN MAJOR VASCULAR SURGERY THE EFFECTS ARE VARIABLE, IN MAJOR VASCULAR SURGERY THE EFFECTS ARE VARIABLE, INFRARENAL AORTIC SURGERY TREATED FELODIPINE FOR 5 DAYS INFRARENAL AORTIC SURGERY TREATED FELODIPINE FOR 5 DAYS BEFORE SURGERY THERE IS INCREASED GFR, IN FIRST 24 HOURS, BEFORE SURGERY THERE IS INCREASED GFR, IN FIRST 24 HOURS, AND IT IS NOT SUSTAINED. IN ANOTHER GROUP OF VASCULAR AND IT IS NOT SUSTAINED. IN ANOTHER GROUP OF VASCULAR SURGERY TREATED WITH NIFEDIPINE HAD INCREASED POST CLAMP SURGERY TREATED WITH NIFEDIPINE HAD INCREASED POST CLAMP SR.CR. CLEARANCE AND LESS REDUCTION IN GFR COMPARED TO LOW SR.CR. CLEARANCE AND LESS REDUCTION IN GFR COMPARED TO LOW DOSE DOPAMINE.DOSE DOPAMINE.

NIFEDIPINE GROUP HAD DECREASED ENDOTHELN AFTER REMOVAL OF NIFEDIPINE GROUP HAD DECREASED ENDOTHELN AFTER REMOVAL OF CLAMP AND HIGH RATIO OF PROSTAGLANDIN F-1 ALPHA TO CLAMP AND HIGH RATIO OF PROSTAGLANDIN F-1 ALPHA TO THROMBOXANE B-2.THROMBOXANE B-2.

CALCIUM CHANNEL BLOCKERS

CALCIUM CHANNEL CALCIUM CHANNEL BLOCKERSBLOCKERS (Cont’d) (Cont’d)

IN CPB FELODIPINE DID NOT AFFECT RENAL RESISTANCE, PAH IN CPB FELODIPINE DID NOT AFFECT RENAL RESISTANCE, PAH EXTRACTION IS HIGH DURING LOW AND HIGH FLOW CPB. IN EXTRACTION IS HIGH DURING LOW AND HIGH FLOW CPB. IN RETROSPECTIVE STUDY WHERE DILTIAZEM USED FOR MYOCARDIAL RETROSPECTIVE STUDY WHERE DILTIAZEM USED FOR MYOCARDIAL PROTECTION EXPERIENCED HIGH SERUM CREATININE LEVELS AND PROTECTION EXPERIENCED HIGH SERUM CREATININE LEVELS AND INCIDENCE OF DIALYSIS WAS HIGH.INCIDENCE OF DIALYSIS WAS HIGH.

THE FLUX OF CALCIUM ACROSS CELL MEMBRANES HAVE BEEN THE FLUX OF CALCIUM ACROSS CELL MEMBRANES HAVE BEEN IMPLICATED IN REPERFUSION AND ISCHEMIC CELL DEATH.IMPLICATED IN REPERFUSION AND ISCHEMIC CELL DEATH.

VERAPAMIL MODULATES NEUTROPHIL INFILTRATION INTO VERAPAMIL MODULATES NEUTROPHIL INFILTRATION INTO ISCHEMIC TISSUES AND TISSUE DAMAGE IS REDUCED.ISCHEMIC TISSUES AND TISSUE DAMAGE IS REDUCED.

AT CELLULAR LEVEL CCB INCREASES GFR BY ALTERING AT CELLULAR LEVEL CCB INCREASES GFR BY ALTERING RELAXATION PHASE OF MESANGIAL CELLS RELAXATION PHASE OF MESANGIAL CELLS

CALCIUM CHANNEL CALCIUM CHANNEL BLOCKERSBLOCKERS (Cont’d) (Cont’d)

ROLE OF CCB IN RENAL ISCHEMIA IS COMPLEX. THEY HAVE ROLE OF CCB IN RENAL ISCHEMIA IS COMPLEX. THEY HAVE CYTOPROTECTIVE EFFECT AND ANTIOXIDANT EFFECT. CYTOPROTECTIVE EFFECT AND ANTIOXIDANT EFFECT.

GRIEF ET.AL., DEMONSTRATED IN RAT MODEL THAT GRIEF ET.AL., DEMONSTRATED IN RAT MODEL THAT INTERRUPTING THE CAL. CASCADE AT ANY OF THE THREE POINTS INTERRUPTING THE CAL. CASCADE AT ANY OF THE THREE POINTS 1) CAL. INFLOW INTO CYTOSOL 2) MITOCHONDRIAL UPTAKE 1) CAL. INFLOW INTO CYTOSOL 2) MITOCHONDRIAL UPTAKE OF CAL. 3) CAL. DEPENDENT ACTIVATION OF CAL. CALMODIN OF CAL. 3) CAL. DEPENDENT ACTIVATION OF CAL. CALMODIN COMPLEX IMPROVED SURVIVAL OF THE CELLS. COMPLEX IMPROVED SURVIVAL OF THE CELLS.

IN LONG TERM TREATMENT MANIDEPINE TUBULAR HYPERTROPHY IS IN LONG TERM TREATMENT MANIDEPINE TUBULAR HYPERTROPHY IS SEEN. THE CLINICAL SIGNIFICANCE HAS TO BE EVALUATEDSEEN. THE CLINICAL SIGNIFICANCE HAS TO BE EVALUATED..

PROSTAGLANDINSPROSTAGLANDINS IN NORMAL KIDNEY PG PLAY A HOMEOSTATIC AND PERMISSIVE ROLE, IN NORMAL KIDNEY PG PLAY A HOMEOSTATIC AND PERMISSIVE ROLE,

INHIBITION OF THEM CAN CAUSE DECREASE RENAL FUNCTION, PGS INHIBITION OF THEM CAN CAUSE DECREASE RENAL FUNCTION, PGS INCREASE GFR, RBF , NATREURISIS AND DECREASED OXYGEN INCREASE GFR, RBF , NATREURISIS AND DECREASED OXYGEN CONSUMPTION AT THICK ASCENDING LOOP OF HENLE.CONSUMPTION AT THICK ASCENDING LOOP OF HENLE.

IN RENAL DYSFUNCTION MODULATION OF PGS TO THROMBOXANE RATIO IN RENAL DYSFUNCTION MODULATION OF PGS TO THROMBOXANE RATIO CAN HAVE FAVOURABLE EFFECTS.CAN HAVE FAVOURABLE EFFECTS.

POST OP INFUSION OF PG-E2 (VASODIALATOR) MAY INCREASE RENAL POST OP INFUSION OF PG-E2 (VASODIALATOR) MAY INCREASE RENAL FUNCTION. FUNCTION.

INFUSION OF ALPROSTADIL IMMEDIATELY AFTER GRAFT INFUSION OF ALPROSTADIL IMMEDIATELY AFTER GRAFT REVASCULARIZATION INCREASES RENAL FUNCTION. REVASCULARIZATION INCREASES RENAL FUNCTION.

CIRRHOSIS PTS RESPOND DIFFERENTLY WITH PGS.CIRRHOSIS PTS RESPOND DIFFERENTLY WITH PGS. PGS IN CARDIAC SURGERY INCREASED GFR.PGS IN CARDIAC SURGERY INCREASED GFR. PGS CAN CAUSE SEVERE HYPOTENSION, MUST BE CAREFULPGS CAN CAUSE SEVERE HYPOTENSION, MUST BE CAREFUL

ATRIAL NATRIURETIC PEPTIDE

ANALOGUES OF ANP HAS BEEN ISOLATED FROM ATRIA AND KIDNEYS.ANALOGUES OF ANP HAS BEEN ISOLATED FROM ATRIA AND KIDNEYS. ANP FROM KIDNEY IS CALLED URODIALATIN.ANP FROM KIDNEY IS CALLED URODIALATIN. ACTIONS OF THIS PEPTIDES MEDIATED BY CYCLIC-GMP.ACTIONS OF THIS PEPTIDES MEDIATED BY CYCLIC-GMP. ACTIVATION OF ANP RECEPTORS INCRESED GFR DUE TO DILATION ACTIVATION OF ANP RECEPTORS INCRESED GFR DUE TO DILATION

OF AFFERENT AND VASOCONSTRICTION OF EFFERENT ARTERIOLE OF AFFERENT AND VASOCONSTRICTION OF EFFERENT ARTERIOLE THEY ALSO CAUSE DECREASE SODIUM REABSORPTION. THEY ALSO CAUSE DECREASE SODIUM REABSORPTION. RELAXATION OF MESANGIAL CELLS CAUSE INCREASED FILTRATION RELAXATION OF MESANGIAL CELLS CAUSE INCREASED FILTRATION

FRACTION. FRACTION. ANP IS AN EFFICIENT ANTAGONIST OF ALL RENAL ANP IS AN EFFICIENT ANTAGONIST OF ALL RENAL

VASOCONSTRICTORS TESTED TO DATE.VASOCONSTRICTORS TESTED TO DATE. URODIALATIN IS A BETTER RENOPROTECTIVE AGENT THAN ANP URODIALATIN IS A BETTER RENOPROTECTIVE AGENT THAN ANP

BECAUSE OF IT S MORE NATRIURESIS AND DIURESIS.BECAUSE OF IT S MORE NATRIURESIS AND DIURESIS.

ATRIAL NATRIURETIC PEPTIDE (Cont’d) (Cont’d)

IT IS RESISTANT TO DEGRADATION BY ENDOPROTEASES.IT IS RESISTANT TO DEGRADATION BY ENDOPROTEASES. NO TACHYPHYLAXIS. NO TACHYPHYLAXIS. LESS HYPOTENSIVE.LESS HYPOTENSIVE. CECEDI ET.AL., USED URODIALATIN AS A RESCUE THERAPY IN CECEDI ET.AL., USED URODIALATIN AS A RESCUE THERAPY IN

ARF PATIENTS AFTER TRANSPLANTATION FOR FIVE DAYS P O ARF PATIENTS AFTER TRANSPLANTATION FOR FIVE DAYS P O AND SHOWED IMPROVED RESULTS.AND SHOWED IMPROVED RESULTS.

FORSSMAN’S GROUP USED URODIALATIN IN CARDIAC PATIENTS FORSSMAN’S GROUP USED URODIALATIN IN CARDIAC PATIENTS AND SHOWED SIGNIFICANT DIURESIS.AND SHOWED SIGNIFICANT DIURESIS.

HERBERT ET. AL., USED URODIALATIN IN PTS OF ARF AFTER HERBERT ET. AL., USED URODIALATIN IN PTS OF ARF AFTER MAJOR ABDOMINAL SURGERIES.MAJOR ABDOMINAL SURGERIES.

IN LIVER TRANSPLANTS URODIALATIN HAD GREATER REDUCTION IN LIVER TRANSPLANTS URODIALATIN HAD GREATER REDUCTION IN SR. CR. LEVELS AND LESS REQUIREMENT OF FRUSEMIDE.IN SR. CR. LEVELS AND LESS REQUIREMENT OF FRUSEMIDE.

DOPAMINE – 1 AGONISTS FENOLDOPAM MESYLATE IS A NOVEL DOPAMINE ANALOGUE FENOLDOPAM MESYLATE IS A NOVEL DOPAMINE ANALOGUE

WITH SPECIFIC DOPAMINE-1 AGONIST ACTIVITY THAT WITH SPECIFIC DOPAMINE-1 AGONIST ACTIVITY THAT STIMULATES POST SYNAPTIC PERIPHERAL DOPAMINE-1 STIMULATES POST SYNAPTIC PERIPHERAL DOPAMINE-1 RECEPTORS. NO ACTION ON DOPAMINE-2 ALPHA AND BETA RECEPTORS. NO ACTION ON DOPAMINE-2 ALPHA AND BETA RECEPTORSRECEPTORS

DOPAMINEDOPAMINEFENOLDOPAMFENOLDOPAM

DOPAMINE-1DOPAMINE-1 ++++++++++++ DOPAMINE-2DOPAMINE-2

++++++ NILNIL ALPHAALPHA++++ NILNIL BETA-1BETA-1

++++++ NILNILBETA-2BETA-2 ++ NILNIL

THE EFFECTS OF FENOLDAPAM IS DOSE DEPENDENT, AT LOW THE EFFECTS OF FENOLDAPAM IS DOSE DEPENDENT, AT LOW DOSES RENAL VASODIALATION AND AT HIGHER DOSES DOSES RENAL VASODIALATION AND AT HIGHER DOSES PERIPHERAL VASODIALATION.PERIPHERAL VASODIALATION.

DOPAMINE – 1 AGONISTSDOPAMINE – 1 AGONISTS (Cont’d)(Cont’d)

SO IT CAUSES HYPOTENSION WITH INCREASED RENAL BLOOD FLOW.SO IT CAUSES HYPOTENSION WITH INCREASED RENAL BLOOD FLOW. IT CAUSES INCREASED CARDIAC AND STROKE VOLUME INDICES IN IT CAUSES INCREASED CARDIAC AND STROKE VOLUME INDICES IN

CCF.CCF. END SYSTOLIC AND ENDDIASTOLIC VOLUMES ARE DECREASED.END SYSTOLIC AND ENDDIASTOLIC VOLUMES ARE DECREASED. IT DECREASES B.P. IN HYPERTENSIVE PATIENTS WHEN COMPARED IT DECREASES B.P. IN HYPERTENSIVE PATIENTS WHEN COMPARED

TO NORMOTENSIVES. TO NORMOTENSIVES. REABSORPTION OF SODIUM , SODIUM AND POTASSIUM EXCHANGE REABSORPTION OF SODIUM , SODIUM AND POTASSIUM EXCHANGE

FALL SIGNIFICANTLY.FALL SIGNIFICANTLY. PATIENTS WITH CHRONIC RENAL INSUFFICIENCY RESPOND PATIENTS WITH CHRONIC RENAL INSUFFICIENCY RESPOND

FAVOURABLY TO FENOLDAPAM.FAVOURABLY TO FENOLDAPAM. IT REVERSES REDUCTION IN RBF AND GFR DURING IPPV.IT REVERSES REDUCTION IN RBF AND GFR DURING IPPV. PRELIMINARY REPORTS SAY THAT FENOLDAPAM MAY BE EFFECTIVE PRELIMINARY REPORTS SAY THAT FENOLDAPAM MAY BE EFFECTIVE

AS RENOPROTECTIVE AGENT IN HIGH RISK PATIENTSAS RENOPROTECTIVE AGENT IN HIGH RISK PATIENTS..

MODULATION OF COMPLEMENT SYSTEM

THERE IS CLEAR EVIDENCE THAT TERMINAL COMPLEMENT COMPLEX THERE IS CLEAR EVIDENCE THAT TERMINAL COMPLEMENT COMPLEX (C5-9) IS A MEDIATOR OF RENAL INJURY.(C5-9) IS A MEDIATOR OF RENAL INJURY.

COMPLEMENT ACTIVATION IS ASSOCIATED WITH IMMUNOLOGICALLY COMPLEMENT ACTIVATION IS ASSOCIATED WITH IMMUNOLOGICALLY MEDIATED RENAL DISEASE SUCH AS LUPUS H S PURPURA, MEDIATED RENAL DISEASE SUCH AS LUPUS H S PURPURA, MEMBRANOUS NEPHROPATHY AND POST STREPTOCOCCAL G N.MEMBRANOUS NEPHROPATHY AND POST STREPTOCOCCAL G N.

COMPLEMENT IS WIDELY ACTIVATED IN CPB, SEPSIS, TRAUMA COMPLEMENT IS WIDELY ACTIVATED IN CPB, SEPSIS, TRAUMA AND AORTIC CROSS CLAMPING. AND AORTIC CROSS CLAMPING.

UNDER NORMAL CIRCUMSTANCES COMPLEMENT ACTIVATION IS WELL UNDER NORMAL CIRCUMSTANCES COMPLEMENT ACTIVATION IS WELL REGULATED .REGULATED .

MEMBRANE INHIBITORS OF COMPLEMENT (MIC) ARE PRESENT IN MEMBRANE INHIBITORS OF COMPLEMENT (MIC) ARE PRESENT IN KIDNEY AND PLAY A VITAL ROLE. KIDNEY AND PLAY A VITAL ROLE.

RENAL INJURY CAN BE AVOIDED BY DEPLETION OF COMPLEMENT RENAL INJURY CAN BE AVOIDED BY DEPLETION OF COMPLEMENT OR BY INFUSION OF MIC.OR BY INFUSION OF MIC.

21 – AMINO STEROIDS (TIRILIZAD)

REACTIVE OXYGEN SPECIES CONTRIBUTE TO REPERFUSION INJURY REACTIVE OXYGEN SPECIES CONTRIBUTE TO REPERFUSION INJURY THROUGH VARIOUS MECHANISMS.THROUGH VARIOUS MECHANISMS.

21-AMINOSTERIODS INHIBIT LIPID PEROXIDATION BY SCAVENGING 21-AMINOSTERIODS INHIBIT LIPID PEROXIDATION BY SCAVENGING LIPID RADICALS AND INHIBITING LIPID RADICAL CHAIN REACTION.LIPID RADICALS AND INHIBITING LIPID RADICAL CHAIN REACTION.

IN ESTABLISHED CASE 21-AMINOSTERIOD IS BETTER THAN SUPER IN ESTABLISHED CASE 21-AMINOSTERIOD IS BETTER THAN SUPER OXIDE DESMUTASE.OXIDE DESMUTASE.

TRANSPLANTATION RELATED OXIDATIVE INJURY IS REDUCED BY 21-TRANSPLANTATION RELATED OXIDATIVE INJURY IS REDUCED BY 21-AMINOSTERIODS AND ACCOMPANIED BY DECREASED EXPRESSIONOF AMINOSTERIODS AND ACCOMPANIED BY DECREASED EXPRESSIONOF CYTOKINES, MAJOR HISTOCOMPATIBILITY COMPLEX ANTIGENS AND CYTOKINES, MAJOR HISTOCOMPATIBILITY COMPLEX ANTIGENS AND INDUCIBLE NITRIC OXIDE SYNTHASE.INDUCIBLE NITRIC OXIDE SYNTHASE.

ALPHA MELANOCYTE STIMULATING ALPHA MELANOCYTE STIMULATING HORMONEHORMONE

ISCHEMIA AND REPERFUSION INJURY IS ACCOMPANIED BY ILFLAMMATORY AND ISCHEMIA AND REPERFUSION INJURY IS ACCOMPANIED BY ILFLAMMATORY AND CYTOTOXIC CASCADE ACTIVATION.CYTOTOXIC CASCADE ACTIVATION.

PREVENTION OF THIS CASCADE DEMONSTRATED TO PROTECT THE KIDNEY.PREVENTION OF THIS CASCADE DEMONSTRATED TO PROTECT THE KIDNEY. ALPHA MELANOCYTE STIMULATING HARMONE REDUCES THE RENAL INJURY AFTER ALPHA MELANOCYTE STIMULATING HARMONE REDUCES THE RENAL INJURY AFTER

ISCHEMIA AND REPERFUSION. ISCHEMIA AND REPERFUSION. IT CAUSES REDUCTION IN BUN, SR. CR., AND HISTOLOGICAL CHANGES IN ANIMALS IT CAUSES REDUCTION IN BUN, SR. CR., AND HISTOLOGICAL CHANGES IN ANIMALS

TREATED WITH THIS HARMONE.TREATED WITH THIS HARMONE. GROWTH HARMONEGROWTH HARMONE: THERE IS A GROWING INTEREST IN CELLULAR REPAIR AND : THERE IS A GROWING INTEREST IN CELLULAR REPAIR AND

REPLACEMENT OF ACUTE INJURY.REPLACEMENT OF ACUTE INJURY. KIDNEY CELLS ELOBARATE AND RESPOND TO VARIOUS GROWTH FACTORS. KIDNEY CELLS ELOBARATE AND RESPOND TO VARIOUS GROWTH FACTORS. EPIDERMAL GROWTH FACTOREPIDERMAL GROWTH FACTOR:: CAUSES ENHANCED CELL REPAIR WITH REDUCTION IN CAUSES ENHANCED CELL REPAIR WITH REDUCTION IN

BUN AND SR.CR.BUN AND SR.CR. SOMATOMEDIN-CSOMATOMEDIN-C GIVEN UPTO 24 HOURS AFTER INJURY SHOWED SAME EFFECTS AS GIVEN UPTO 24 HOURS AFTER INJURY SHOWED SAME EFFECTS AS

ABOVE.ABOVE. THYROXIN THYROXIN AND FIBROBLAST GROWTH FACTOR AND TRANFORMING GROWTH FACTOR-B ARE AND FIBROBLAST GROWTH FACTOR AND TRANFORMING GROWTH FACTOR-B ARE

UNDER INVESTIGATIONUNDER INVESTIGATION..

DOPAMINE

LOW DOSE DOPAMINE LOW DOSE DOPAMINE (LDD)(LDD) HAS BEEN USED TO PREVENT OR TREAT ARF HAS BEEN USED TO PREVENT OR TREAT ARF WITH OUT CONVINCING EVIDENCE. WITH OUT CONVINCING EVIDENCE.

2-5 MICS/KG/MIN IS USED TO AVOID SYSTEMIC CARDIOVASCULAR 2-5 MICS/KG/MIN IS USED TO AVOID SYSTEMIC CARDIOVASCULAR EFFECTS BY STIMULATING ONLY DOPAMINE RECEPTORS IN KIDNEY.EFFECTS BY STIMULATING ONLY DOPAMINE RECEPTORS IN KIDNEY.

LDD HAS BEEN SHOWN TO INCREASE URINE FLOW IN SICK POST-LDD HAS BEEN SHOWN TO INCREASE URINE FLOW IN SICK POST-OPERATIVE PATIENTS.OPERATIVE PATIENTS.

BUT IT FAILED TO DEMONSTRATE BENEFICIAL EFFECTS IN MAJOR BUT IT FAILED TO DEMONSTRATE BENEFICIAL EFFECTS IN MAJOR SURGERIES.SURGERIES.

SIDE EFFECTS:SIDE EFFECTS: TACHYCARDIA, ARRYTHMIAS, INCREASED RT AND LT TACHYCARDIA, ARRYTHMIAS, INCREASED RT AND LT VENTRICULAR AFTER LOAD, INCREASED MYOCARDIAL OXYGEN VENTRICULAR AFTER LOAD, INCREASED MYOCARDIAL OXYGEN CONSUPTION, ANGINA, ISCHAEMIA, DECREASED HYPOXIC RESPIRATORY CONSUPTION, ANGINA, ISCHAEMIA, DECREASED HYPOXIC RESPIRATORY DRIVE, INCREASED PULMONARY SHUNT, INCREASED PCWP, DRIVE, INCREASED PULMONARY SHUNT, INCREASED PCWP, HYPONATREMIA, HYPOKALEMIA, HYPOPHOSPHOTEMIA,AND DEPLETION OF HYPONATREMIA, HYPOKALEMIA, HYPOPHOSPHOTEMIA,AND DEPLETION OF VOLUME.VOLUME.

DOPAMINE (Cont’d) (Cont’d)

RECPTORRECPTOR LOCATIONLOCATION ACTIONACTION

DA-1DA-1 POST- SYNAPTICPOST- SYNAPTIC V.DIL V.DIL DA-2DA-2 PRE- SYNAPTIC PRE- SYNAPTICDECREASEN.A.RELDECREASEN.A.REL B-1 ADR B-1 ADR POST- SYNAPTIC POST- SYNAPTIC

CARD. STIM.CARD. STIM. B-2 ADR B-2 ADR POST- SYNAPTICPOST- SYNAPTIC V.DILV.DILALPHA-1ALPHA-1 POST- SYNAPTICPOST- SYNAPTIC

V. CONSTR.V. CONSTR. ALPHA-2ALPHA-2 PRE- SYNAPTIC PRE- SYNAPTIC DECREASE N.A. DECREASE N.A.

EFFECTS OF DOPAMINE ON RENAL PHYSIOLOGY

STRUCTURESTRUCTURE EFFECTEFFECT WHOLE KIDNEYWHOLE KIDNEY INCREASED RBFINCREASED RBF

INCREASED GFRINCREASED GFRNATREURESISNATREURESISDIURESISDIURESIS

GLO. HEMODYN. GLO. HEMODYN. AFFER. ART. DIL. AFFER. ART. DIL.VARI. EFFECT EFF.ART.VARI. EFFECT EFF.ART.NO EFFECT ON FILT.CO-EFFNO EFFECT ON FILT.CO-EFF JUXTA JUXTA

GLOM. APP.GLOM. APP. ALT.GLOM.FEED BACK ALT.GLOM.FEED BACKDECREASED RENIN RELEASDECREASED RENIN RELEAS PROX . PROX .

TUBULETUBULE INHI. OF NA – K-ATP ASEINHI. OF NA – K-ATP ASENA-H-EXCHANGE, NA-PO4-NA-H-EXCHANGE, NA-PO4- COTRANSPORT AND ANTA. COTRANSPORT AND ANTA. OF ANGIOTENSIN-2 OF ANGIOTENSIN-2

T.A.L.T.A.L. INHI. OF NA-K-ATP ASEINHI. OF NA-K-ATP ASE COLLECT. COLLECT. DUCTDUCT ANTA. OF ADH. ANTA. OF ADH.

FUROSEMIDEFUROSEMIDE

IT IS REGULARLY USED WHEN THERE IS DECREASED URINE OUT- IT IS REGULARLY USED WHEN THERE IS DECREASED URINE OUT- PUT.PUT.

IT MAY FLUSH THE TUBULAR DEBRIS INCREASE RBF, DECREASED IT MAY FLUSH THE TUBULAR DEBRIS INCREASE RBF, DECREASED OXYGEN CONSUMPTION AND DECREASED RENO-VASCULAR OXYGEN CONSUMPTION AND DECREASED RENO-VASCULAR RESISTANCE.RESISTANCE.

THERE IS NO CONVINCING EVIDENCE THAT IT PROTECTS FAILING THERE IS NO CONVINCING EVIDENCE THAT IT PROTECTS FAILING KIDNEY.KIDNEY.

INSTEAD LARGE DOSES CAUSE –OTO TOXICITY, SEVERE INSTEAD LARGE DOSES CAUSE –OTO TOXICITY, SEVERE HYPOVOLEMIA, ELECTROLYTE DISTURBANCE AND CAN CAUSE RENAL HYPOVOLEMIA, ELECTROLYTE DISTURBANCE AND CAN CAUSE RENAL FAILURE.FAILURE.

IF AT ALL IT SHOULD BE GIVEN EARLY WITH PROPER IF AT ALL IT SHOULD BE GIVEN EARLY WITH PROPER MONITORING.MONITORING.

MANNITOL OSMOTIC DIURETICOSMOTIC DIURETIC DOES NOT ENTER CELLSDOES NOT ENTER CELLS FILTERED COMPLETELY BY GLOMERULIFILTERED COMPLETELY BY GLOMERULI NO APPRECIABLE REABSORPTION BY RENAL TUBULESNO APPRECIABLE REABSORPTION BY RENAL TUBULES INCREASED URINARY EXCRETION OF WATERINCREASED URINARY EXCRETION OF WATER DECREASED SODIUM REABSORPTIONDECREASED SODIUM REABSORPTION FLUSHING OF DEBRISFLUSHING OF DEBRIS DECREASED ENDOTHELIAL SWELLINGDECREASED ENDOTHELIAL SWELLING MAINTAINS OPTIMAL INTRAMEDULLARY BLOODFLOWMAINTAINS OPTIMAL INTRAMEDULLARY BLOODFLOW DECREASED 0-2 DEMANDDECREASED 0-2 DEMAND SCAVENGES EXTRA CELLULAR FREE HYDROXYL RADICALSSCAVENGES EXTRA CELLULAR FREE HYDROXYL RADICALS IN CLINICAL SETTING, MANNITOL ROLE IN RENO-PROTECTION IS IN CLINICAL SETTING, MANNITOL ROLE IN RENO-PROTECTION IS

NOT WELL ESTABLISHEDNOT WELL ESTABLISHED DISADVANTAGES:DISADVANTAGES:SUDDEN INCREASE IN INTRAVASCULAR VOLUME, SUDDEN INCREASE IN INTRAVASCULAR VOLUME,

DEPLETION OF WATER AND HYPOVOLEMIA AND PULM.EDEMA.DEPLETION OF WATER AND HYPOVOLEMIA AND PULM.EDEMA.

VOLUME LOADINGVOLUME LOADING

VOLUME LOADING OPTIMALLY WITH ACCURATE MONITORING OF VOLUME LOADING OPTIMALLY WITH ACCURATE MONITORING OF PCWP HAS DEFINITELY DECREASED MORTALITY OF ARF 33%-10% . PCWP HAS DEFINITELY DECREASED MORTALITY OF ARF 33%-10% . INTRA OP URINE OUT PUT IS NOT A PREDICTOR OF POST OP. INTRA OP URINE OUT PUT IS NOT A PREDICTOR OF POST OP. RENAL FUNCTION. MAINTAINANCE OF ADEQUATE VOLUME STATUS RENAL FUNCTION. MAINTAINANCE OF ADEQUATE VOLUME STATUS IS CORNER STONE OF PROPHYLAXIS AGAINST ARF.IS CORNER STONE OF PROPHYLAXIS AGAINST ARF.

KIDNEY PERFUSATEKIDNEY PERFUSATE THE SOLUTION CONSISTS OF THE SOLUTION CONSISTS OF 2500 UNITS OF HEPARIN, 100 ML 2500 UNITS OF HEPARIN, 100 ML

OF 20% MANNITOL IN 500 ML OF RLOF 20% MANNITOL IN 500 ML OF RL WHICH IS COOLED TO 4 WHICH IS COOLED TO 4 DEGREES CELSIUS, IT IS PERFUSED INTO THE KIDNEY. DEGREES CELSIUS, IT IS PERFUSED INTO THE KIDNEY. HYPOTHERMIA IS ALSO USED TO PRESERVE HARVESTED ORGANS HYPOTHERMIA IS ALSO USED TO PRESERVE HARVESTED ORGANS FOR TRANSPLANTATIONFOR TRANSPLANTATION..

ENDO VASCULAR AORTIC ENDO VASCULAR AORTIC STENTINGSTENTING

NISHIMURA ET. AL., SUGGESTED THAT ENDO VASCULAR STENTING NISHIMURA ET. AL., SUGGESTED THAT ENDO VASCULAR STENTING CAN MINIMIZE RISK OF MAJOR SURGERY ON THE KIDNEY. THE CAN MINIMIZE RISK OF MAJOR SURGERY ON THE KIDNEY. THE PROCEDURE CAN BE DONE UNDER L A. PROCEDURE CAN BE DONE UNDER L A.

MANAGEMENT OF ARF IN THE MANAGEMENT OF ARF IN THE POST-OPERATIVE PERIODPOST-OPERATIVE PERIOD

ARF IN THE POST OPERATIVE PERIOD CARRIES HIGH ARF IN THE POST OPERATIVE PERIOD CARRIES HIGH MORTALITY 50-70% MORTALITY 50-70%

EARLY INVOLVEMENT OF NEPHROLOGIST IS CRUCIALEARLY INVOLVEMENT OF NEPHROLOGIST IS CRUCIAL TREATMENT DIFFERS WITH TYPE OF RENAL FAILURE TREATMENT DIFFERS WITH TYPE OF RENAL FAILURE

AND SINGLE OR MULTI ORGAN INVOLVEMENTAND SINGLE OR MULTI ORGAN INVOLVEMENT ARF IS DIVEDED INTO 1) PRE 2) POST 3) INTRA - ARF IS DIVEDED INTO 1) PRE 2) POST 3) INTRA -

RENAL RENAL ARF IS DIAGNOSED BY INCREASED CREATININE LEVELS ARF IS DIAGNOSED BY INCREASED CREATININE LEVELS

AND BUN AND BUN DIFFERENCES BETWEEN PRE-RENAL AND ATNDIFFERENCES BETWEEN PRE-RENAL AND ATNPRE RENALPRE RENAL ATNATN URINE SODIUMURINE SODIUM 10 mmol 10 mmol >20mmol >20mmolFRAC.EXCRE.OF SODIUM FRAC.EXCRE.OF SODIUM <19%<19% >19%>19%URINE/SERUM OSMO.URINE/SERUM OSMO. >1.8>1.8 <1.1<1.1BUN/CR. RATIOBUN/CR. RATIO >15>15 <10<10

PATHOPHYSIOLOGYPATHOPHYSIOLOGY

SEVERE PROLONGED SURGERIES, DELAYED CARDIAC SEVERE PROLONGED SURGERIES, DELAYED CARDIAC RESUCITATION, SEVERE SEPSIS LEADS TO ATN.RESUCITATION, SEVERE SEPSIS LEADS TO ATN.

GLOMERULI ARE NORMAL.GLOMERULI ARE NORMAL. TUBULES ARE DAMAGED, DILATED.TUBULES ARE DAMAGED, DILATED. CELLULAR LOSS.CELLULAR LOSS. AREAS OF DENUDED BASEMENT MEMBRANE.AREAS OF DENUDED BASEMENT MEMBRANE. OTHER CELLS ARE FLATTENED.OTHER CELLS ARE FLATTENED. MITOSIS IS SEEN.MITOSIS IS SEEN. CASTS MAY BE OBSERVED.CASTS MAY BE OBSERVED.

SEVERITY SCORING - ARFSEVERITY SCORING - ARF( CLEVELAND CLINIC SCORING)( CLEVELAND CLINIC SCORING)

VARIABLEVARIABLE ODDS RATIOODDS RATIO SCORESCORE MALE GENDERMALE GENDER 2.42.4 22 INTUBATION /IPPVINTUBATION /IPPV 2.52.5 33 BLOOD STATUSBLOOD STATUS

PLATELETS<50,000PLATELETS<50,000LEUCOCYTES<2500LEUCOCYTES<2500 2.12.1 33 BLEEDING BLEEDING DIATHESISDIATHESIS

BILIRUBIN > 2BILIRUBIN > 2 2.12.1 33 ABSECENCE OF SURGERYABSECENCE OF SURGERY 22 11 NO. OF ORGANS FAILURENO. OF ORGANS FAILURE

11 11 11 2 - 32 - 31.31.3 22 5 - 7 5 - 7 2.52.533

BUN < 50BUN < 50 1.8 1.8 11 BUN > 50 BUN > 50 22 2 2 SR. CR.SR. CR.< 2< 2 4.8 4.8 00 2 - 2 -

55 2.62.6 11 >5>5 1133

MANAGEMENTMANAGEMENT

PREVENTION OF DAMAGEPREVENTION OF DAMAGE

CONSERVATIVE LINE OF MANAGEMENTCONSERVATIVE LINE OF MANAGEMENT

RENAL REPLACEMENT THERAPYRENAL REPLACEMENT THERAPY

MANAGEMENT (Cont’d…) MANAGEMENT (Cont’d…)

PREVENTION OF DAMAGE: PREVENTION OF DAMAGE: IDEAL WAY TO PREVENT RENAL DAMAGE AND ALLOW RENAL IDEAL WAY TO PREVENT RENAL DAMAGE AND ALLOW RENAL

RECOVERY IS TO PROVIDERECOVERY IS TO PROVIDE 1.1. ADEQUATE SUPPLY OF ADEQUATE SUPPLY OF OXYGENATED BLOOD BY INOTROPES I.V.FLUIDS AND OXYGENATED BLOOD BY INOTROPES I.V.FLUIDS AND MECHANICAL VENTILATION.MECHANICAL VENTILATION.

22.. AVOIDING AND PROMPT TREATMENT OF SEPSIS: AVOIDING AND PROMPT TREATMENT OF SEPSIS: ASEPTIC TECHNIQUES CARE OF INTRACATHS, URINARY ASEPTIC TECHNIQUES CARE OF INTRACATHS, URINARY CATHETERSCATHETERS ANTIBIOTIC THERAPY, IDENTIFYING OCCULT ANTIBIOTIC THERAPY, IDENTIFYING OCCULT INFECTION BYINVASIVE METHODS .INFECTION BYINVASIVE METHODS .

33..NEPHROTOXIC MATERIALS: AVOID OR USE NEPHROTOXIC MATERIALS: AVOID OR USE WITH CARE LIKE WITH CARE LIKE ACE INHIBITORS AND CONTRAST ACE INHIBITORS AND CONTRAST MEDIA. MEDIA.

4.4.PIGMENTURIA: RAPID DESTRUCTION OF MUSCLE PIGMENTURIA: RAPID DESTRUCTION OF MUSCLE LEADS TO NEPHROTOXIC MATERIALS, THIS MYOGLOBIN IS LEADS TO NEPHROTOXIC MATERIALS, THIS MYOGLOBIN IS NON-ENZYMATICALLY CONVERTED TO FERRIHEMATE NON-ENZYMATICALLY CONVERTED TO FERRIHEMATE PREVENT MUSCLE DESTRUCTION AND PREVENT ACIDOSIS.PREVENT MUSCLE DESTRUCTION AND PREVENT ACIDOSIS.

5.5.ETHYLENE GLYCOL USED IN SUICIDE IT IS ETHYLENE GLYCOL USED IN SUICIDE IT IS CONVERTED INTO FORMALDEHYDE AND OXALATE. CONVERTED INTO FORMALDEHYDE AND OXALATE. TREATED BY ETHANOL OR H.D.TREATED BY ETHANOL OR H.D.

CONSERVATIVE /MEDICALCONSERVATIVE /MEDICALMANAGEMENT MANAGEMENT

* 1) FLUID VOLUME:1) FLUID VOLUME: * EUVOLEMIA IS ESSENTIAL, EUVOLEMIA IS ESSENTIAL,

* HYPER-VOLEMIA AND DEHYDRATION AVOIDED,HYPER-VOLEMIA AND DEHYDRATION AVOIDED,

* ADULT INSENSIBLE LOSS PER DAY IS 1 LT, IN ADULT INSENSIBLE LOSS PER DAY IS 1 LT, IN FEVER WITH EACH DEGREE RISE NEEDS EXTRA FEVER WITH EACH DEGREE RISE NEEDS EXTRA 500 ML,500 ML,

* REPLACEMENT OF FLUID LOST IN DRAINS,REPLACEMENT OF FLUID LOST IN DRAINS,

* TREATMENT MAY BE ENTERAL OR PARENTERAL TREATMENT MAY BE ENTERAL OR PARENTERAL DEPENDING ON THE CONDITION OF THE PATIENT.DEPENDING ON THE CONDITION OF THE PATIENT.

HYPERKALEMIA HYPERKALEMIA (MANAGEMENT Contd)(MANAGEMENT Contd)

RESULTS IN DECREASED RENAL FUNCTION FROM RESULTS IN DECREASED RENAL FUNCTION FROM DAMAGED CELLS, LEAKAGE FROM CELLS AS A RESULT DAMAGED CELLS, LEAKAGE FROM CELLS AS A RESULT OF OUBAIN LIKE UREMIC TOXINS AND ACIDOSIS.OF OUBAIN LIKE UREMIC TOXINS AND ACIDOSIS.

SERUM K+ >6.5 MEQ SHOULD BE REGARDED AS SERUM K+ >6.5 MEQ SHOULD BE REGARDED AS DANGEROUS , NEEDS PROMPT TREATMENT.DANGEROUS , NEEDS PROMPT TREATMENT.

HEART IS AT RISK, EKG SHOWS PROLONGED P-R HEART IS AT RISK, EKG SHOWS PROLONGED P-R INTERVAL, PEAK ‘T’ WAVES, WIDE QRS COMPLEXES, INTERVAL, PEAK ‘T’ WAVES, WIDE QRS COMPLEXES, ‘P’ WAVE DIS-APPEARS, BRADYCARDIA AND ‘P’ WAVE DIS-APPEARS, BRADYCARDIA AND VENTRICULAR FIBRILLATION. VENTRICULAR FIBRILLATION.

TR:TR: a) AVOID K+ SPARING AGENTS LIKE ACE a) AVOID K+ SPARING AGENTS LIKE ACE INHIBITORS, SPIRONOLACTONE AND DARROW’S INHIBITORS, SPIRONOLACTONE AND DARROW’S SOLUTION b) TREATING ACIDOSIS, c) G-I SOLUTIONS, SOLUTION b) TREATING ACIDOSIS, c) G-I SOLUTIONS, d) I.V. CALCIUM, e) RECTAL OR ORALd) I.V. CALCIUM, e) RECTAL OR ORAL RESINS, RESINS, f)DIURETICS, g)I.V. SOLBUTAMOL AND h) FINALLY f)DIURETICS, g)I.V. SOLBUTAMOL AND h) FINALLY DIALYSIS.DIALYSIS.

UREMIA MANAGEMENTUREMIA MANAGEMENT

UREMIA UREMIA DEPENDS ON CATABOLISM. DEPENDS ON CATABOLISM. AVOID OR TREAT INFECTION.AVOID OR TREAT INFECTION.

PROTECTION AGAINST GASTRIC BLEEDING AND PROTECTION AGAINST GASTRIC BLEEDING AND SUBSEQUENT DIGESTION (STRESS ULCERS, PLATELET SUBSEQUENT DIGESTION (STRESS ULCERS, PLATELET DYSFUNCTION) TREATED WITH H-2 BLOCKERS.DYSFUNCTION) TREATED WITH H-2 BLOCKERS.

H-2 BLOCKERS CAN CAUSE BACTERIAL COLONIOZATION H-2 BLOCKERS CAN CAUSE BACTERIAL COLONIOZATION

DUE TO INCREASED PH.DUE TO INCREASED PH.

EARLY NUTRITION PREVENTS INFECTION, DECREASES EARLY NUTRITION PREVENTS INFECTION, DECREASES CATABOLISM AND INCREASES WOUND HEALING.CATABOLISM AND INCREASES WOUND HEALING.

HYPER / HYPOTENSIONHYPER / HYPOTENSION

MANAGEMENTMANAGEMENT

HYPERTENSION IS NOT PROBLEMATIC HYPERTENSION IS NOT PROBLEMATIC TREATED ROUTINELY WITH ANTI-TREATED ROUTINELY WITH ANTI-HYPERTENSIVE DRUGS.HYPERTENSIVE DRUGS.

HYPOTENSION MAY BE PROBLEMATIC HYPOTENSION MAY BE PROBLEMATIC DUE TO DUE TO

IMPAIRED CARDIAC FUNCTION AND IMPAIRED CARDIAC FUNCTION AND PERIPHERAL VASODILATION.PERIPHERAL VASODILATION.

METABOLIC ACIDOSIS METABOLIC ACIDOSIS MANAGEMENT MANAGEMENT

METABOLIC ACIDOSIS IS DUE TO INCREASED METABOLIC ACIDOSIS IS DUE TO INCREASED CATABOLISM, DECREASED EXCRETION BY CATABOLISM, DECREASED EXCRETION BY KIDNEY.KIDNEY.

ACIDOSIS IS DETREMENTAL TO BODY. IT LEADS ACIDOSIS IS DETREMENTAL TO BODY. IT LEADS TO INCREASE PROTEIN CATABOLISM, TO INCREASE PROTEIN CATABOLISM, DEPRESSED MYOCARDIAC CONTRACTILITY AND DEPRESSED MYOCARDIAC CONTRACTILITY AND MINERAL LOSS FROM BONE.MINERAL LOSS FROM BONE.

SERUM BI-CARBONATE LEVELS <15 Meq / lt OR SERUM BI-CARBONATE LEVELS <15 Meq / lt OR ARTERIAL PH < 7.2 DENOTE SEVERITY OF ARTERIAL PH < 7.2 DENOTE SEVERITY OF ACIDOSIS , TREATED WITH SODA BI-CARB.ACIDOSIS , TREATED WITH SODA BI-CARB.

ANAEMIAANAEMIA ANAEMIA IS DUE TO UREMIA, DECREASED ANAEMIA IS DUE TO UREMIA, DECREASED

ERYTHROPOIETIN, SEPSIS, SHORTENED RBC LIFE SPAN. ERYTHROPOIETIN, SEPSIS, SHORTENED RBC LIFE SPAN.

TREATED WITH ERYTHROPOIETIN AND BLOOD TREATED WITH ERYTHROPOIETIN AND BLOOD

TRANSFUSION.TRANSFUSION.

BONE METOBOLISMBONE METOBOLISM

HYPOCALCEMIA, HYPERPHOSPHOTEMIA, INCREASED HYPOCALCEMIA, HYPERPHOSPHOTEMIA, INCREASED PARATHYROID HARMONE, DECREASED ACTIVATION OF PARATHYROID HARMONE, DECREASED ACTIVATION OF VIT-D. VIT-D.

TREATED WITH DECREASED PHOSPHATE INTAKE AND TREATED WITH DECREASED PHOSPHATE INTAKE AND ORAL PHOSPHATE BINDING AGENTS.ORAL PHOSPHATE BINDING AGENTS.

RENAL REPLACEMENT RENAL REPLACEMENT THERAPYTHERAPY

CRITERIACRITERIA FOR RENAL REPLACEMENT THERAPY FOR RENAL REPLACEMENT THERAPY INCLUDEINCLUDE1) INABILITY TO CONTROL HYPERVOLEMIA1) INABILITY TO CONTROL HYPERVOLEMIA

2) INABILITY TO CONTROL HYPERKALEMIA 2) INABILITY TO CONTROL HYPERKALEMIA 3) INABILITY TO CONTROL ACIDOSIS 3) INABILITY TO CONTROL ACIDOSIS 4) INABILITY TO CONTROL UREMIA. 4) INABILITY TO CONTROL UREMIA.

THERE ARE THREE FORMS OF RRTTHERE ARE THREE FORMS OF RRT

1) INTERMITTENT HAEMODIALYSIS1) INTERMITTENT HAEMODIALYSIS

2) CONTINUOUS HEMOFILTRATION2) CONTINUOUS HEMOFILTRATION

3) PERITONEAL DIALYSIS3) PERITONEAL DIALYSIS

INTERMITTENT INTERMITTENT HEMODIALYSISHEMODIALYSIS

BLOOD IS WITHDRAWN AT THE RATE OF ABOUT BLOOD IS WITHDRAWN AT THE RATE OF ABOUT 200 ml/min200 ml/min MIXED WITH HEPARIN PASSED THROUGH A DIALYSER PERFUSED MIXED WITH HEPARIN PASSED THROUGH A DIALYSER PERFUSED WITH DIALYSATE SOLUTION AT THE RATE OF WITH DIALYSATE SOLUTION AT THE RATE OF 500 ml /min500 ml /min IN THE IN THE OPPOSITE DIRECTION TO BLOOD FLOW.OPPOSITE DIRECTION TO BLOOD FLOW.

THESE TWO ARE SEPARATED BY A SEMIPERMEABLE MEMBRANE.THESE TWO ARE SEPARATED BY A SEMIPERMEABLE MEMBRANE. UREMIC TOXINS LEAVE THE BLOOD BY DIFFUSION, UREMIC TOXINS LEAVE THE BLOOD BY DIFFUSION,

ELECTROLYTES EQUILIBRATE DEPENDING ON THEIR CON. ELECTROLYTES EQUILIBRATE DEPENDING ON THEIR CON. DIFFERENCE.DIFFERENCE.

EACH SESSION LOSTS FOR 3-4 HOURS ONCE A DAY 3-TIMES A EACH SESSION LOSTS FOR 3-4 HOURS ONCE A DAY 3-TIMES A WEEK.WEEK.

ADVANTAGES:ADVANTAGES: HIGH CLEARANCE OF UREMIC TOXINS, RAPID HIGH CLEARANCE OF UREMIC TOXINS, RAPID CORRECTION OF ELECTROLYTES, SHORT PERIOD OF EXPOSURE CORRECTION OF ELECTROLYTES, SHORT PERIOD OF EXPOSURE TO ANTI COAGULANTS.TO ANTI COAGULANTS.

DISADVANTAGES DISADVANTAGES ::DEDICATED TRAINED PERSONNEL NEEDED, DEDICATED TRAINED PERSONNEL NEEDED, ANTICOAGULATION, RAPID SHIFTS OF ELECTROLYTES AND ANTICOAGULATION, RAPID SHIFTS OF ELECTROLYTES AND TOXINS, RAPID SHIFT OF FLUIDS IN TISSUE COMPARTMENTS, TOXINS, RAPID SHIFT OF FLUIDS IN TISSUE COMPARTMENTS, INTRACELLULAR FLUID SHIFTS CAUSING CEREBRAL EDEMA AND INTRACELLULAR FLUID SHIFTS CAUSING CEREBRAL EDEMA AND DECREASED CEREBRAL PERFUSION.DECREASED CEREBRAL PERFUSION.

CONTINUOUS HEMOFILTRATIONCONTINUOUS HEMOFILTRATION

CONTINUOUS ARTERIO VENOUS HEMOFILTRATION CONTINUOUS ARTERIO VENOUS HEMOFILTRATION (CAVH).(CAVH). ARTERY AND VEIN ARE CANNULATED , ARTERIAL BLOOD IS ARTERY AND VEIN ARE CANNULATED , ARTERIAL BLOOD IS

HEPARINISED PASSED THROUGH A FILTER AND RETURN TO THE HEPARINISED PASSED THROUGH A FILTER AND RETURN TO THE PATIENT.PATIENT.

THE FLUID REMOVED IS 1 lt/Hr AND IS USUALLY REPLACED THE FLUID REMOVED IS 1 lt/Hr AND IS USUALLY REPLACED DOWN-STREAM THE FILTER WITH A COMMERCIAL PREPARATION.DOWN-STREAM THE FILTER WITH A COMMERCIAL PREPARATION.

HERE THERE IS INCREASED PERMEABILITY, SO INFLAMMATORY HERE THERE IS INCREASED PERMEABILITY, SO INFLAMMATORY MEDIATORS ARE CLEARED FASTER.MEDIATORS ARE CLEARED FASTER.

FILTER LIFE LOSTS FOR 1-4 DAYS.FILTER LIFE LOSTS FOR 1-4 DAYS. CONSTANT SLOW CORRECTION OF ELECTROLYTES.CONSTANT SLOW CORRECTION OF ELECTROLYTES. DISADVANTAGES:DISADVANTAGES: NEEDS ARTERIAL CANNULATION, DEPENDS ON NEEDS ARTERIAL CANNULATION, DEPENDS ON

B.P., CONTINUED ANTI-COAGULATION.B.P., CONTINUED ANTI-COAGULATION. CVVH:CVVH: CONTINUOUS VENO VENOUS HEMOFILTRATION. ADDITION CONTINUOUS VENO VENOUS HEMOFILTRATION. ADDITION

OF PUMP IN CVVH, NO NEED OF ARTERIAL CANNULATION.OF PUMP IN CVVH, NO NEED OF ARTERIAL CANNULATION. CVVHD:CVVHD: CONTINUOUS VENO VENOUS HEMO DIALYSIS. DIALYSIS CONTINUOUS VENO VENOUS HEMO DIALYSIS. DIALYSIS

FLUID PASS THROUGH THE FILTER IN OPPOSITE TO BLOOD FLOW FLUID PASS THROUGH THE FILTER IN OPPOSITE TO BLOOD FLOW @ 1000ml /Hr.@ 1000ml /Hr.

PERITONEAL DIALYSIS GANTER 1923 . GANTER 1923 .

CONTROL ON FLUID BALANCE, NEEDS INTACT PERITONEUM .CONTROL ON FLUID BALANCE, NEEDS INTACT PERITONEUM .

THE DIALYSIS FLUID IS PLACED INTO THE PERITONEAL CAVITY THE DIALYSIS FLUID IS PLACED INTO THE PERITONEAL CAVITY THROUGH A CATHETER AND AFTER SPECIFIED TIME IT IS THROUGH A CATHETER AND AFTER SPECIFIED TIME IT IS DRAINED.DRAINED.

FLUID BALANCE IS ACHIEVED BY VARYING THE OSMOLALITY FLUID BALANCE IS ACHIEVED BY VARYING THE OSMOLALITY OF THE DIALYSIS FLUID BY ADDING GLUCOSE.OF THE DIALYSIS FLUID BY ADDING GLUCOSE.

THE PROCESS IS MACHINE DRIVEN OR MANUAL.THE PROCESS IS MACHINE DRIVEN OR MANUAL.

ADVANTAGES:ADVANTAGES: SIMPLE, REMOVAL OF INFLAMMATORY SIMPLE, REMOVAL OF INFLAMMATORY MEDIATORS GOOD, NO NEED OF ANTI-COAGULATION.MEDIATORS GOOD, NO NEED OF ANTI-COAGULATION.

DISADVANTAGES:DISADVANTAGES: NOT EFFICIENT IN LOW BLOOD PRESSURES, NOT EFFICIENT IN LOW BLOOD PRESSURES, MORE OF DIALYSIS FLUID IS NEEDED, INFECTION, LESS MORE OF DIALYSIS FLUID IS NEEDED, INFECTION, LESS TIGHT.TIGHT.

REFERENCESREFERENCES 1] ANAESTHESIOLOGY CLINICS OF NORTH 1] ANAESTHESIOLOGY CLINICS OF NORTH

AMERICA: Anesthesia and renal considerations by AMERICA: Anesthesia and renal considerations by JEROME F. OHARA, VOL.18 No.4, Dec.2000.JEROME F. OHARA, VOL.18 No.4, Dec.2000.

2] CLINICS IN CHEST MEDICINE: Acute Renal 2] CLINICS IN CHEST MEDICINE: Acute Renal Failure In Intensive Care Unit by ANDREW Failure In Intensive Care Unit by ANDREW BRIGLIA, ANDS EMIL P. PEGANINI.Vol.20, No.2 , BRIGLIA, ANDS EMIL P. PEGANINI.Vol.20, No.2 , June.1999.June.1999.

British Journal of Intensive Care,British Journal of Intensive Care, Vol.8, Vol.8, No.5, Oct.1998. Pages 163-No.5, Oct.1998. Pages 163-