RENAL FUNCTION TEST AND DIAGNOSIS & MANAGEMENT OF ARF

RENAL FUNCTION TEST AND DIAGNOSIS & MANAGEMENT OF PERIOPERATIVE ARF: 

R ENAL FUNCTION TEST AND DIAGNOSIS & MANAGEMENT OF PERIOPERATIVE ARF Presenter : Moderator : Dr. K. Basumatary Dr. R. K. Bhattacharyya PGT MD Anaesthesiology Prof. Dept. of Anaesthesiology AMC, Dibrugarh AMC, Dibrugarh Date: 19-08-2011

INTRODUCTION: 

“Lack of urine output in the acutely hypovolaemic patient is renal success, not a renal failure.” - Dr. Ronald V. Maier Acute renal failure (ARF) is seen commonly in the perioperative period and in the ICU. It is not a primary disease as that of the ARDS, but a complication of other disease processes, most notably severe sepsis and septic shock, and reflects the high morbidity and mortality of the primary diseases. It is therefore imperative to either prevent its occurrence or recognize its presence by various useful renal function tests and treat it as soon as efficiently as possible. INTRODUCTION

RENAL FUNCTION TESTS : 

Terms: 1. Anuria: Urine flow – zero or < 50ml/day 2. Oliguria: Urine flow - <0.5 ml/kg/hr. or <15 ml/hr. 3. Nonoliguria : Urine flow – 15 to 80 ml/hr. 4. Polyuria : Urine flow - >80 ml/hr. RENAL FUNCTION TESTS

A. CLINICAL MARKERS OF RENAL FUNCTION: : 

1. Perioperative Oliguria: Urine flow <0.5 ml/kg/hr. Sign of renal dysfunction Pre-renal is usually in response to hypovolaemia or surgical stress Abrupt anuria is due to postrenal obstruction which leads to acute renal failure (ARF). A. CLINICAL MARKERS OF RENAL FUNCTION:

Oliguria contd.: 

RIFLE criteria for acute kidney injury(AKI ): Risk – SCr 1.5 × baseline, Urine Output <0.5 ml/kg/hr. - -× 6 hrs. Injury - SCr 2 × baseline, - - do - - ×12 hrs. Failure – SCr 3 × baseline ( ≥4mg/dl or, acute rise ≥0.5 mg/dl) – do - - × 24 hrs. Loss of complete renal function - - - - - - × 4 weeks End stage kidney disease - - - - - - - × 3 months But this does not take into consideration the non-oliguric renal failure (commonest) of perioperative AKI. 2. Blood Urea Nitrogen (BUN): Urea is ammonia byproduct from liver Hepatic deamination splits of amide group from aminoacids forming ammonia which enters to arginine cycle producing urea. Oliguria contd.

BUN contd.: 

Urea nitrogen is a small uncharged molecule not protein bound rapidly filtered by glomeruli. Normal range is 5 – 10 mg/dl on normal serum creatinine (0.5-1.0 mg/dl). Hence the ratio 10:1 Causes of ↑BUN – pre-renal azotemia ( BUN:Sr . Cr. > 20:1) Absorption of blood from GIT Corticosteroid therapy Major trauma Sepsis BUN contd.

BUN contd.: 

Causes of ↓BUN – Protein depletion ( severe malnutrition) Severe liver disease 3. Serum Creatinine ( SCr ): Reflects the balance between creatinine production by mucle and excreation by the kidney Production varies with Muscle mass Physical activity Protein intake Catabolism BUN contd.

SCr contd.: 

Normally SCr is 0.5 to 1.5 mg/dl SCr 4 – 8 mg/dl represents 50% reduction in GFR by which time renal insufficiency is well established. Causes of ↑ SCr – All the oliguric renal damages Ketoacidosis Barbiturates Cephalosporins Cimetidine & trimethoprim by blocking secretion in the tubules SCr contd.

SCr contd.: 

N- acetylcysteine , an antioxidant, has the renoprotective function which can reduce SCr SCr is not reliable marker when GFR is rapidly changing as in aging. 4. Cystatin – C: Cystatine , a protease inhibitor released by all nucleated cells Completely filtered, not secreted by tubules Not affected by muscle mass, age or gender More accurate predictor of GFR change Affected in smokers, inflammation and immunosuppressive therapy SCr contd.

B. ASSESSMENT OF GFR:: 

1. Serum creatinine based nomograms : Based on population studies Avoids necessity of timed urine collection (140 – age) × wt. in kg. GFR = SCr (mg/dl) × 72 For females result is multiplied by 0.85 to obtain derived GFR Disadv . – overestimates in obese, oedematous , cachectics due to weight as a variable in the equation. Normal GFR is around 125 ml/min B. ASSESSMENT OF GFR:

2. Renal clearance:: 

Commonly used technique Compounds filtered by glomerulus neither secreted nor absorbed by renal tubules are taken Based on Fick principle – “amount of substance ‘x’ excreted by the kidney equals the amount delivered in arterial supply minus the amount in the venous return” Excretion x = delivery x – return x Substance ‘x’ delivered = Art. plasma conc. ( Pax ) × RBF Returning ‘x’ from kidney = Ven. Plasma conc.( Pvx ) × RBF Urinary excretion rate = Urinary conc. ( Ux ) × Urine flow rate/min (V) 2. Renal clearance:

Renal clearance contd.: 

Hence, ( Pax × RBF) = ( Pvx × RBF) + ( Ux × V) In practice RBF and venous return is not measured, instead expressed in the concept of ‘Clearance’. Clearance (C) – virtual volume of plasma (in ml) cleared of substance ‘x’ per unit time (min). Hence, Renal arterial plasma conc. = Urinay excretion rate Or, Pax × C = Ux × V Ux × V Urinary excretion rate Or, Cx = = Pax Plasma concentration Renal clearance contd.

3. Inulin clearance:: 

Inulin is an inert polyfructose sugar Completely filtered by glomerulus Neither secreted nor reabsorbed Plasma (ml) cleared of inulin per minute represents the GFR (ml/min) Method of calculation – 30 to 50 mg/kg inulin iv bolus followed by continuous infusion given to establish a steady state plasma conc. of 15 – 20 mg/dl. Bladder flushed with air to eliminate any pooled urine Timed urine collection (~30 mins .) done Urine and plasma inulin conc. (U IN , P IN ) measured & inulin clearance (C IN ) is calculated. 3. Inulin clearance:

Inulin C conted.: 

U IN × V C IN = = GFR P IN Normal values: 110 – 140 ml/min/1.73 m2 in males & 95 – 125 ml/min/1.37 m2 in females. Gold standard for GFR estimation but laborious, seldom used clinically Large changes in blood glucose interfere measurements. 4. Creatinine Clearance ( Ccr ): Creatinine, an endogenous end product of creatine phosphate metabolism normally generated from muscle at a very uniform rate. Inulin C conted .

Creatinine C contd.: 

Handled by kidney in a similar manner to inulin . Creatinine clearance ( Ccr ) provides a simple, inexpensive bedside estimation of GFR. Ucr × V Ccr = = GFR Pcr More accurate than Sr. Cr. alone, because GFR change immediately alters creatinine excreation rate. Normal level: 88 – 148 ml/min with Sr.Cr . conc. 0.9 – 1.5 mg/dl. Diurnal variation up to 25% around mean and is high in afternoon hours. Fluctuates widely as normal Ccr is related to body surface area and weight. Creatinine C contd.

Ccr contd.: 

Limitations: 20% secreted by the proximal tubules. Hence, overestimates GFR. ↓ GFR → ↑ tubular secretion of creatinine. Trimethoprim, H2-blockers, salicylates block creatinine tubular secretion → ↑ Sr. Cr. & ↓ Ccr . Very ↑ Sr. Cr. causes excretion of Cr. into the gut and undergoes extrarenal metabolism by intestinal flora. Usefullness : Serial estimation is an usefull clinical guide to renal function alteration & prognosis. Variability loss - ↓ GFR, means deteriorating renal function. Guides the dosing of renally excreted nephrotoxic drugs e.g. – gentamicin , tobramycin , amikacin , cyclosporin etc. Ccr contd.

5.Plasma Clearance:: 

Measurement of the rate of disappearance of a substance from plasma completely eliminated by glomerular filtration. Doesn’t require simultaneous urine collection. Done by i.v. bolus injection of a marker and measurement of multiple plasma levels after achievement of a steady-state plasma concentration of the marker. Markers used – Inulin Non-radioactive Iothalamate 51 Cr-EDTA 99 Tc-DTPA Radio-isotopes 125 I-iodothalamate 5.Plasma Clearance:

C. TUBULAR FUNCTION TESTS: 

Measure urinary concentrating ability and sodium and urea handling. They can distinguish oliguria due to hypovolaemia (prerenal) from that due to tubular injury (ATN). 1. Urinary concentrating ability: Very sensitive for tubular function. In prerenal state urine osmolarity increases markedly. In ATN urine concentrating ability is lost usually 24 – 48 hrs. prior to S.Cr . or BUN starts increasing. C. TUBULAR FUNCTION TESTS

2. Urine to plasma osmolar ratio:: 

Normal tubular response to hypovolaemia is urine concentration. Urine osmolality becomes > 450 mos /kg. Normal plasma osmolality is 280 – 300 mos /kg. Urine : plasma (U:Posm) osmolar ratio >1.5 - indicates prerenal syndrome. U:Posm = 1.0 → loss of concentrating ability ( isosthenuria ) – indicates tubular damage and established ARF. Diuretics can induce this condition in a prerenal state. 2. Urine to plasma osmolar ratio:

3. Free water clearance (CH2O):: 

Measure of renal water regulation by tubular dilution or concentration of urine. Positive free water clearance – free water cleared by tubules in response to hypervolaemia. Negative free water clearance – free water retained in response to hypovolaemia. C H 2 O varies from +18 L to – 8 L/day. Calculated as follows: U OSM × V C OSM = P OSM (ml/min) C OSM = Osmolar clearance of solutes 3. Free water clearance (C H 2 O ):

CH2O contd.: 

Then osmolar clearance is subtracted from urine flow rate to get C H 2 O. C H 2 O = V – C OSM (ml/min) C H 2 O + ve – urine is diluted, V>C OSM C H 2 O – ve - urine is concentrated, V<C OSM Tubular conservation of water (TC H 2 O ) – negative C H 2 O or free water retention represents the volume needed to be added to the urine to make its osmolality equal to that of plasma. Onset of ATN → loss of urine concentrating ability → isosmotic urine, C H 2 O approaches to zero (±0.25 ml/min). U:P OSM gives more information than C H 2 O for distinguishing prerenal and intra-renal oliguria. C H 2 O contd.

4. Water conservation:: 

It is the urine to plasma creatinine ratio ( Ucr:Pcr ) that represents the proportion of water filtered by the glomerulus that is abstracted by tubules. 98% water is abstracted normally, Ucr > Pcr Ucr:Pcr increases 100 folds in severe prerenal state & reduces in intrarenal (or ATN). 5. Sodium conservation: Dehydration & hypovolaemia - ↑Na reabsorbtion . Prerenal - ↓↓ U Na <20 mEq /L – correctable with iv volume restoration. Severe sepsis & hepatorenal syndrome – refractory oliguria with ↓ U Na . 4. Water conservation:

Na & urea conservation contd.: 

Due to endotoxaemia there is renal vasoconstriction and avid Na reabsorption. ATN – Na conservation lost, U Na >40 – 80 mEq /L. 6. Fractional excretion of sodium ( FE Na ): Na clearance as a percentage of creatinine clearance C Na FE Na = × 100% Ccr ( U Na × V) P Na U Na / P Na Or, FE Na = × 100% = × 100% ( Ucr × V) Pcr Ucr / Pcr Na & urea conservation contd.

FENa contd.: 

Requires spot blood and urine sample only, no timed urine collection required. Hypovolaemia (prerenal) – FE Na <1% of Ccr ARF (ATN or renal) – FE NA > 2% of Ccr FE Na ↑ in diuretic therapy, post-operative Na mobilization even in normal tubular functon . 7. Fractional excretion of urea nitrogen (FE UN ): Related to water reabsorption in proximal tubule (PT). More sensitive and specific than FE Na , because of its little influence by diuretic therapy. FE Na contd.

FEUN contd.: 

U UN / B UN FE UN = × 100% Ucr / Pcr Prerenal - < 35%, renal or ARF 50 - 65% even in the presence of loop diuretic as they are acting in ascending loop of Henle . Falasy - Acetazolamide , mannitol – PT diuretics, and highly catabolic state ( ↑ urea production) induce osmotic diuresis themself render FE UN inaccurate . FE UN contd.

8. Indices of tubular injury:: 

i . β 2 -Microglobulin: Small protein, component of histocompatibility complex, filtered by glomerulus , undergoes partial tubular absorption. In glomerular injury serum level increses and urine level decreases. Utilized as an early sign of renal transplant rejection. In tubular injury serum level decreases and urine level increases. ii. Urinary N-acetyl β -D- glucosaminidase (NAG): Used as a sign of renal transplant rejection. 8. Indices of tubular injury:

iii. Nutrophil gelatinase – associated lipocalin (NGAL):: 

Small polypeptide, expressed in proximal tubule, undergoes dramatic upregulation in ischaemic tubular injury. In ischaemic reperfusion injury it increases 3 – 4 times within 2 – 3 hrs. and upto 10,000 folds by 24 hrs. iii. Nutrophil gelatinase – associated lipocalin (NGAL):

D. RENAL HAEMODYNAMICS: 

1. Renal Plasma Flow(RPF) & Renal Blood Flow (RBF): p- Aminohippurate (PAH), an organic ion, completely cleared from plasma in a single pass through the kidney, hence C PAH represents RPF. A steady state plasma conc. of 2 mg/dl after infusion & careful timed catheter urine collection is done & calculated as follows:- U PAH × V C PAH = = RPF = 660ml/min/1.73m2 P PAH RBF = RPF/(1 – Hct .) = 945 ml/min D. RENAL HAEMODYNAMICS

2. Filtration Fraction(FF):: 

Fraction of RPF filtered by the glomeruli. GFR GFR = 125 ml/min FF = = 0.2 RPF = 600 ml/min RPF ↑ FF → efferent arteriolar constriction, afferent dilation ↓ FF → afferent arteriolar constriction, efferent dilation 3. Total renal blood flow (TRBF): i . Flow probes & dopplar analysis: TRBF (ml/min) = blood velocity (cm/min) × vessel area (cm2) 2. Filtration Fraction(FF):

ii. Thermodilution:: 

Done by placing a thermistor in renal vein and applying cold saline. iii. Contrast USG: Done by injecting sonicated albumin microspheres into aorta & recorded by USG images of kidney & aorta and TRBF calculated mathematically. ii. Thermodilution :

ACUTE RENAL FAILURE (ARF): 

Pathophysiology of renal failure: Kidneys receive 20 – 25% of cardiac output and get 10% of the total body oxygen uptake. Cortex receives 90 – 95% and medulla receives 5 – 10% of total RBF and has an average PaO 2 of 8 mmHg. Hence, easily suffers hypoxia. Renal autoregulation maintains GFR over a wide range of blood pressures ( 80 – 180 mmHg). Glomerular ultrafiltration is a balance between vasodilators and vasoconstrictors. Oxygen extraction is much higher in medulla due to active water and salt reabsorption. ACUTE RENAL FAILURE (ARF)

Table: Distribution of renal blood flow between cortex and medulla: 

Parameters Cortex Medulla Percent of renal blood flow 94 6 Blood flow (ml/gm/min) 5 0.03 PO 2 (mmHg) 50 8 O 2 extraction ratio (VO 2 /DO 2 ) 0.18 0.79 Table: Distribution of renal blood flow between cortex and medulla

Pathogenesis contd.: 

Perioperative renal failure depends upon the surgery, pre-operative and intraoperative haemodynamics and renal conditions as in diabetics where there is 10 fold greater risk in the presence of hypovolaemia. All intravenous and volatile agents affect renal function by decreasing cardiac output (CO) and blood pressure (BP). Central neuraxial block upto T 4 level reduces sympathetic tone to kidney resulting in decrease of RBF & GFR. Positive pressure mechanical ventilation reduces RBF Major surgeries → extensive 3 rd space loss → hypovolaemia & ↓RBF Pathogenesis contd.

Fig. – Pathogenesis of Acute Renal Failure: 

Pre-renal Renal/intrinsic Post-renal ARF Hypovolaemia Renal hypoperfusion Obstruction to the Hypotension an/or Nephrotoxins urinary collection Acute interstitial nephritis system Acute glomerulonephritis or vasculitis Renal hypotension Elevation of intraureteral pressure transmitted to the renal parenchyma Activation of compensatory systemic RENAL HAEMODYNAMIC and renal responses CHANGES AND STRUCTURAL DAMAGE Increase in tubular Increase in renal blood flow reabsorption of Na and H 2 O followed by reduction FUNCTIONAL RENAL FAILURE OBSTRUCTIVE ARF Afferent Efferent Capillary Leaking back Tubular arteriolar arteriolar surface area and of filtrate obstruction vasoconstriction vasoconstriction glomerular permeability ORGANIC ACUTE RENAL FAILURE Fig. – Pathogenesis of Acute Renal Failure

Pathogenesis contd.: 

Acute Renal Success: When thick ascending loop of Henle becomes ischemic NaCl reabsorption ceases, urine concentration is lost. Intractable polyuria should result. But, increased delivery of NaCl to the macula densa trigers angiotensin -mediated arteriolar constriction, which decreases GFR, induces oliguria, conserves intravascular volume and protects the organism from dehydration – so-called acute renal success. Pathogenesis contd.

Risk Factors:: 

Patient factors Perioperative factors Advanced age Haemodynamic instability-hypotension Major vascular surgey Hypovolaemia (oliguria) Atherosclerosis Diuretic therapy CABG, other cardiac surgery Surgical oedema Hypertension Preoperative starvation CCF Gastric aspiration/vomiting Biliary surgery/jaundice Peritonitis/ ileus /obstruction Chronic renal disease Diarrhoea /bowel preparation Cirrhosis of liver Prolonged tissue exposure Diabetes mellitus Blood loss Myeloma Hypoxia Nephrotoxic drugs Tissue damage and inflammation Pre- eclampsia / eclampsia Ischaemia & reperfusion Sepsis Major burns Polytrauma Muscle breakdown Pancreatitis Massive blood transfusion and transfusion reaction Risk Factors:

Types of Renal Failure:: 

Traditionally oliguria is defined as a urine output of <0.5 ml/kg/hr. or <400 ml/day or <16.6 ml/hr. Anuria is an absence of urine or <50 ml/day. Reduction in urine output is not necessarily renal failure. Oliguria may be an external sign of hypovolaemia, needs correction. Restoration of blood volume and pressure may increase urine output showing kidneys to be in good condition. Types of Renal Failure:

1. Pre-renal:: 

Any cause proximal to kidneys which decreases RBF leads to oliguria. Can usually be corrected by correcting underlying disorders. Prolonged and severe pre-renal condition can lead to renal injury and failure. 2. Renal or Intra-renal injury: Intrinsic renal disorders such as acute tubular necrosis (ATN), interstitial nephritis (AIN), glomerulonephritis and vasculitis cause renal injury. 1. Pre-renal:

RF types contd.: 

ATN is an oxidative injury to renal tubular epithelial cells with sloughing of cells into the lumen of the tubules. Sloughed cells obstruct tubules, increases pressure in the proximal tubules (PT) reducing net filtration pressure across the glomerular capillaries resulting reduced GFR, known as tubulo-glomerular feedback. AIN – an inflammatory condition of interstitium leads to ARF without oliguria. Most often due to drug hypersensitivity. Difficult to distinguish from ATN. RF types contd.

RF types contd.: 

Chart: Drugs that can cause AIN Antibiotics CNS Drugs Diuretics Aminoglycosides Carbamazepine Acetozolamide Amphotericin B Phenobarbital Furosemide Cephalosporins Phenytoin Thiazides Fluoroquinolones Penicillins NSAIDs Others Sulfonamides Aspirin Acetaminophen Vancomycin Ibuprofen ACE inhibitors Ketorolac Iodinated dyes Naproxen Ranitidine RF types contd.

RF types contd. : 

Drug induced AIN – fever, rash, eosinophilia. Onset – usually 2 wks. after start of drug. Eosinophil & leukoccyte casts in urine – very characteristic. Renal biopsy can secure the diagnosis. Rx – offending agent discontinuation, - oral prednisolone 0.5-1.0 mg/kg/day,1-4 wks Complete resolution takes months. 3. Post-renal condition: Obstruction distal to renal parenchyma. Abrupt anuria post-op suggests post-renal condition. RF types contd.

Chart: Causes of Oliguria: 

Chart: Causes of Oliguria Pre-renal Renal Post-renal Hypovolaemia Hypotension Poor cardiac output states Cardiomyopathy , Aortic stenosis , Dissecting aneurysm Mechanical ventilation Pre-existing renal damage Renal vascular disease Renal vasoconstriction Drugs that impair renal autoregulation Hypoxia From pre-renal causes Renal vein thrombosis Circulatory shock Severe sepsis Nephrotoxins : Aminoglycosides Amphotericin B Chemotherapeutic agents NSAIDS Contrast media Tissue injury Haemoglobinuria Myoglobinuria Uric acids ( tumour lysis ) Inflammatory nephritis Glomerulonephritis Interstitial nephritis Polyarteritis Myeloma Surgery Papillary necrosis Retroperitoneal mass Urethral stricture Bladder neck obstruction Prostatic hypertrophy Pelvis surgery with accidental bilateral ureteral ligation Raised intra-abdominal pressure Blocked drainage system Bilateral renal or ureteric calculi or in solitary kidney with complete obstruction Blood clots

EVALUATION OF OLIGURIA: 

1. Central Venous Catheter: Central venous pressure (CVP) of 1 - 2 mmHg – a definitive proof of hypovolaemia. In ICU CVP of 10 – 12 mmHg in ventilator dependant patients can represent hypovolaemia. Central venous oxyhaemoglobin saturation (ScvO 2 ) <50% indicates low cardiac output (CO), when SaO 2 & Hb % levels are normal. Respiratory variation in BP – Adequate filling vol. – IPPV ↑stroke vol., CO & SBP. Inadequate ’’ ’’ ’’ ↓ ’’ ’’ ’’ ’’ EVALUATION OF OLIGURIA

2. Evaluation of the urine:: 

i . Urine microscopy: Abundant tubular epithelial cells, epithelial cell casts → ATN ( pathognomonic ). White cell casts → interstitial nephritis. Pigmented casts → myoglobinuria . ii. Spot urine Na examination: Renal hypoperfusion → ↑ Na reabsorption → ↓ Na excretion → U Na < 20 mEq /L → Pre-renal condition. Intrinsic renal disease → ↓ Na reabsorption → ↑ Na loss → U Na >40 mEq /L → Renal condition. 2. Evaluation of the urine:

Urine evaluation contd.: 

Exception: U Na > 40 mEq /L also occurs in – Pre-renal condition superimposed on CRF. Elderly patients Ongoing diuretic therapy. They are known as obligatory Na loosers . iii. Fractional Excretion of Na ( FE Na ): Na clearance as percentage of creatinine clearance. FE Na < 1% = pre-renal condition FE Na > 2% = renal condition Exception: In ATN due to myoglobinuria where FE Na < 1% Urine evaluation contd.

3. Serum creatinine conc.: S.Creatinine & Ccr for differentiating Acute Renal Injury and Acute Renal Failure : 

3. Serum creatinine conc.: S.Creatinine & Ccr for differentiating Acute Renal Injury and Acute Renal Failure Condition Serum Creatinine Creatinine Clearance Renal Injury 2 × baseline > 50% decrease Renal Failure 3 × baseline or acute rise ≥0.5 mg/dl to ≥4 mg/dl ≥ 75% decrease

Table: Investigations to help differentiate pre-renal and renal causes of renal failure. : 

Table: Investigations to help differentiate pre-renal and renal causes of renal failure. Investigations Pre-renal Renal Urinary Na ( mEq /L) <20 >40 Fractional excretion of Na (%) <1 >2 Urinary osmolarity ( mOsm /L) >400 250 – 300 Urine creatinine/Plasma creatinine >40 <20 Urine/Plasma osmolarity >1.5 <1.1

MANAGEMENT OF PERIOPERATIVE ARF:: 

Preparation for surgery: Check the adequacy of hydration, cardiac output and blood pressure. Look at the daily intake and output charts. Use a large bore cannula for iv fluid resuscitation. Administer oxygen if necessary. Essential monitoring includes – ECG, NIBP and pulse oximetry . IBP and CVP should be considered. MANAGEMENT OF PERIOPERATIVE ARF:

Preparation for surgey contd.: 

Echocardiography and pulmonary artery catheter, helpful if available. Shift to the ICU for monitoring and perioperative stabilization if required. Fluid challenge – On suspicion of hypovolaemia immediate volume infusion required. 500 – 1,000 ml of crystalloid or 300 – 500 ml of colloid infused over 30 mins . (CVP, Pulmonary artery cathter , echocardiography may be required). Continued until response or concerned of overload. Preparation for surgey contd .

Fluid challenge contd.: 

No favor for crystalloid or colloid. Hypoalbuminics – 5% albumin should be considered. Minimum mean arterial pressure to preserve renal autoregulation : Normal patients - > 70 mmHg (>50 mmHg for some) Hypertensives - > 85 mmHg Intra-op management: Intra abdominal pressure > 20 mmHg (normal 0 – 17 mmHg) anuria can result from direct compression on the renal pelvis. Seen in emergency laparotomies (30%) for a massive intra-abdominal bleeding such as leaking abdominal aortic aneurysm, intestinal distention, Fluid challenge contd.

Intra-op management contd.: 

paralytic ileus and ascitis . Improvement occurs only after decompression. Probable mechanisms: Reduced venous return. Compression of renal vein with reflex renal artery vasoconstriction. Elevation of renal tubular pressure with a decrease in the filtration gradient and an increase in rennin, aldosterone and ADH production. Intra-abdominal pressure may be measured by instilling 50 ml saline into the bladder via a Foley’s catheter, clamp it off and measure the manometric pressure of Intra-op management contd.

Management contd.: 

of the fluid within the bladder via a needle inserted into the catheter lumen. ↑ intra-abdominal pressure may give false high CVP leading to underfilling of the patient. On first recognition of deteriorating renal function immediately eliminate or reduce the nephrotoxic drug dose or change to other drugs. With normal blood pressure and hypovolaemia is not an issue drastically cut down the IV fluid therapy, to prevent overload. The use of dopamine and diuretics is controversial. Management contd.

Post-op management :: 

Reduce acid administration (commonly administered in the form of 0.9% NaCl solution which has a pH of 5). Reduce potassium, magnesium, phosphates in maintenance IV and enteral feeds. Avoid NSAID S in the post-op period. Start enteral feeds as early as possible and maximize enteral nutrition as there is now evidence that outcomes are better in patients on enteral rather than parenteral nutrition. Post-op management :

Fig.: Treatment algorithm for acute oliguria during perioperative period.: 

Patient at risk of ARF? Yes No Administer a Continue fluid challenge management Diuresis occurs? Yes No Continue management Further fluid administration hazardous? Yes No CVP/Pulmonary artery occlusion pressure Administer additional fluid Normal to low Elevated / MAP low Administer additional fluid Dopamine? / Nor adrenaline? Diuresis? Yes No Continue management Continue dopamine, nor adrenaline Add diuretics Other inotropes? Fig.: Treatment algorithm for acute oliguria during perioperative period.

Other management issues:: 

Use of Diuretics- Rationale of their use rests on the assumption that they decrease oxygen consumption in the tubular cells by inhibiting the high energy trans-cellular sodium transport (Na-K ATPase) and thus prevents ischaemic cell injury. Loop diuretics vasodilate cortical vessels by liberating prostaglandin and improve oxygenation. Augmentation of tubular blood flow may reduce intratubular obstruction and back leak of filtrate, thus rapidly accelerating resolution of ARF. Other management issues:

Diuretics contd.: 

In established ARF - no benefit of loop diuretics due to reduced transport by plasma proteins, reduced RBF and chronic chloride depletion. Outcome – better in non-oliguric than oliguric failure. Harmful effect of frusemide – interstitial nephritis, hearing loss. Should be given only after adequately filled and BP is adequate or will cause further damage due to hypoperfusion. Diuretic effect of frusemide depends mainly on urinary excretion rate than to its plasma concentration - continuous infusion is more effective. Indication : Frusemide resistance – when 80 mg given iv results <2 ltrs. urine in 4 hrs. Diuretics contd.

Diuretics contd.: 

Doses: Start with 100 mg frusemide i.v. bolus followed by continuous infusion at 40 mg/hr. Double the dose every 12 hrs. if needed to achieve output ~ 100 ml/hr. Dose should not exceed 170 mg/hr. Mannitol 0.5 – 1 gm/kg may sometimes be considered but ineffective in esblished renal failure. Mannitol increases plasma volume, ANP , PGI 2 levels, reduces oncotic pressure, blood viscosity and haematocrit , all of which may improve renal perfusion & GFR. Mannitol reduces tubular cell swelling due to ischemia from any reason thereby removes compression of interstitial and vascular spaces and improves renal perfusion. Diuretics contd.

Diuretic contd.: 

Thus mannitol increases both RBF and GFR and give high solute and water load to be reabsorbed by tubules which causes high energy expenditure and oxygen demand, so that it may do more harm than good in situation where there is impaired oxygen delivery. High solute load needs to be balanced with its ability to inhibit tubular resorptive process by decreasing medullary hypertonicity . High doses of mannitol may cause renal artery vasospasm and increased RVR resulting in decreased renal perfusion impairing renal function. Diuretic contd.

Dopamine:: 

Low dose 1 – 3 mcg/kg/min – diuretic and natriuretic . No benefit in ARF patients (hence, bad medicine ) . Deleterious effect – Decreased splanchnic blood flow Inhibition of T-cell function Inhibition of TSH release Tachyarrhythmias Respiratory drive depression. Noradrenaline: Markedly improves MAP and GFR usually seen in high output – low resistance septic shock. Dopamine:

Dopamine contd.: 

Urine flow reappears with restoration of systemic haemodynamics and renal function improves, shows that renal function is not worsened by septic shock. Effective dose range in sepsis: 0.2 – 1.3 mcg/kg/min Adrenaline: Increases arterial pressure by increasing cardiac index and stroke volume in patients who fail to respond to fluid and other vasopressors . Detrimental to splanchnic blood flow and causes transient decreases in pH and increase the P CO 2 . Dopamine contd.

Dobutamine:: 

Used to improve cardiac output. It causes peripheral vasodilatation by its action on vascular β 2 receptors and is usually used along with noradrenaline. Fenoldopam mesylate : A dopamine analogue. Stimulates post synaptic D-1 receptor only. Adv. over dopamine are – High dopaminergic potency, Lack of tachyarrhythmia effect, Can be safely infuse through a peripheral vein. Dobutamine :

Calcium channel blockers: : 

It is believed that CCB exert direct vascular effect with preservation of renal autoregulation and enhanced recovery of RBF, GFR and natriuresis. High doses may compromise the haemodynamics . Treatment for Hyperkalemia: Should be initiated if serum potassium is > 6.5 mmol /L or ECG changes are present. Intervention is important or cardiac compromise may occur. Calcium channel blockers:

Chart showing the various treatment modalities of hyperkalemia:: 

Treatment Mechanism of action Onset of action Duration of action Side effects Calcium - iv Gluconate 5-10 ml 10% solution Chloride 3-5 ml 10% solution Directly antagonizes effects of potassium on the heart Immediate Brief Avoid if being treated with digitalis Insulin 5 U Actrapid in 100 ml 20% Dextrose over 30 - 60 mins Shifts potassium into cells Prompt 4 – 6 hrs. Hyperglycaemia , Hypoglycaemia Beta agonist Salbutamol 5 mg nebulized Shifts potassium intracellularly Prompt Short Requires nebulizers Sodium bicarbonate 50 – 100 meq if acidotic Shifts potassium into cells Prompt Short Possible sodium overload Ion exchange resin Calcium resonium 15 gm PO/30 gm PR 8 hrly Removes potassium from body 1 -2 hrs Sodium overload Dialysis or haemofiltration Removes potassium from body Prompt Requires vascular access Chart showing the various treatment modalities of hyperkalemia :

Dialysis:: 

Indication :- Oliguria: UO < 200 ml/day Anuria: UO < 50 ml/12 hrs. Volume overload Hyperkalemia: K+ >6.5 mmol /L Severe acidaemia : pH <7.0 Uraemia ( azotemia – urea conc. >30 mmol /L) with a change in mentation ( uraemic encephalopathy), pericarditis , pleuritis or bleeding. Plasma Na abnormality: >155 mmol /L or <120mmol/L Drug overdose with dialyzable toxins. BUN and creatinine clearance 100 mg/dl and <15 ml/min respectively are the cut off margins to start dialysis. Dialysis:

Types of Dialysis:: 

Peritoneal dialysis (PD) – not usually considered for post-op general surgical patient with abdominal pathology or respiratory compromise. Haemodialysis (HD) – difficult to do especially in the hypotensive post-op or septic patient due to high speed flow required for countercurrent exchange. Continuous arteriovenous haemofiltration (CAVH) – arteriovenous pressure difference is the main head of blood flow through the filter. Continuous venovenous haemofiltration (CVVH) – slow method of solute and fluid removal, results in a largely haemodynamically stable milieu and can remove large quantity of cytokines which reduce progression to multi-organ failure. Types of Dialysis:

CONCLUSION: 

Acute renal failure is a common and in many cases it is a preventable and/ or eminently treatable problem seen in the operation theatres and intensive care units. In sepsis, appearance of oliguria usually heralds the beginning of multiple organ failure, which can be viewed as gradual process of dying. The physicians treating the critically ill patient should be well versed in the diagnosis and management of renal failure. CONCLUSION

References:: 

1. Sladen RN. : Renal Physiology, Miller’s Anesthesia 7 th Ed. 2. Nightingale P & Edward DJ : Critical Care, Wylie and Churchill Davidson’s A Practice of Anaesthesia 5 th & 6 th Ed. 3. Marino PL : The ICU Book 3 rd Ed. 4. Jacob R : Acute Renal Failure, Indian Journal of Anaesthesiology, Vol.-7, 2003 References:

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