경희의료원 마취통증의학과 R4 조 인배

Kidney dysfunction in the postoperative periodBritish Journal of Anesthesia 95(1): 20-32(2005)J. W. Sear 경희의료원 마취통증의학과 R4 조 인배

Perioperative ARF : high incidence of morbidity, mortality various incidence with different surgical procedures, definition lacking - rescue therapy, randomized clinical trials, • Review : physiology, pharmacology of kidney renal function tests causes of postoperative renal dysfunction prevention and treatments effect of postoperative renal dysfunction

Renal blood flow : its control and the effects of hypoxia • Kidney : receives about 20% of cardiac output oxygen delivery - 80ml/min/g blood flow is not uniform(cortex receiving more than 90%) oxygen consumption : 10% of total body utilization low arteriovenous oxygen content difference  oxygen reserve

highly sensitive to hypoperfusion  frequent complication of hypotension. • paradox : high blood supply and low extraction of oxygen, yet high incidence of renal damage  renal medulla : low oxygen tension : high oxygen requirement for tubular reabsorption • Medullary oxygenation : balanced by control mechanisms. outer medullary region susceptible to hypoxia  acute tubular necrosis(ATN)-specially the mTAL

Hypoxia and renal damage • heterogeneity of flow and oxygen requirement,  cortex is about 50 mm Hg higher medulla • mTAL region is vulnerable to hypoxic injury  induced by 40-50% decrease in renal blood flow • main determinant of medullary oxygen requirement : rate of active reabsorption of salt and water in the mTAL region.  When this process is inhibited by loop diuretics,  increase in the medullary tissue oxygen pressure

Mediators can affect medullary blood flow  alter the magnitude of any ischaemic injury (i)Vasodilators: nitric oxide, prostaglandin E2, adenosine, dopamine, urodilatin (ii) Vasoconstrictors: endothelin, angiotensin II, ADH (iii) Tubulo-glomerular feedback: insufficient reabsorption of sodium  glomerular afferent constriction  reducing filtration (iv) Medullary tubular growth factors: these include insulin-like growth factor I, epidermal growth factor, and tumour necrosis factor

salt and water reabsorption is one factor predisposing to medullary hypoxic damage : when there is adequate circulating volume and salt loading  reducing the need for urine concentration  reduces medullary oxygen utilization  therapeutic advantage • In contrast, the hypoxic injury will be made worse by other factors(antibiotics, renal hypertrophy, NSAIDs, angiotensin II, calcium ions, myoglobin, hyperbilirubin -aemia, and contrast media) cf) Restoration of RBF  10% of normal GFR  tubular obstruction and back leak tubulo-glomerular feedback, excessive stimulation of the renin-angiotensin system  profound prolonged ARF.

The kidney: devoid of β2 receptor increase in circulating catecholamines(epinephrine)  vasoconstriction via the α1-receptors activation of the renin-angiotensin system • As a result, despite a normal TRBF, intramedullary ischaemia may occur (mTAL region : very sensitive to ischaemia)

Renal function tests

GFR : single most important marker • tubular function: urinary β-NAG, α-1-microglobulin, retinol binding protein, plasma pro-, anti-inflammatory cytokines. • ideal endogenous compound(for GFR) - release into the blood stream at a constant rate - free filtration by the glomerulus - no reabsorption or secretion by the renal tubules - exclusive elimination via the kidney  first-line test of glomerular function has been creatinine clearance.

Cystatin C • creatinine clearance is the best predictive marker : but not practical in the operating theatre.  serum creatinine as an alternative : but confounding factors (age, sex, muscle mass, diet) • cystatin C : alkaline non-glycosylated protein, produced by all nucleated cells. freely filtered through the glomerular membrane completely reabsorbed and degraded by the proximal tubular cells.

Dharnidharka and colleagues - comparing serum cystatin C and creatinine as markers for GFR : cystatin C to be superior, respond more rapidly to changes in GFR • In contrast to creatinine clearance, the reference range values for cystatin C : identical for men, women and children, : not influenced by muscle mass.  not altered in the elderly when muscle mass falls

Perioperative fluid balance • two separate aspects of the normal fluid balance : preoperative fluid depletion : peroperative factors - blood and fluid losses, - neuroendocrine response to anaesthesia and surgery.

Effects of anaesthesia • cause peripheral vasodilatation, myocardial depression. • to maintain organ perfusion : vasoconstrictors fluid replacement is needed. • In kidney : also need to maintain adequate efferent arteriolar vasoconstriction(responsible for the glomerular filtration pressure)  under the control of angiotensin II : receiving chronic angiotensin converting enzyme inhibitors or angiotensin II receptor antagonist treatment  may develop a significant decrease in the perfusion pressure with decreased urine production. • Neuraxial anaesthesia also causes vasodilatation

Effects of surgery • catabolic hormones and cytokines. • main effect is the increased secretion of ADH • Increases in aldosterone, glucocorticoids  cause sodium, water retention and potassium loss.  Thus alteration in overall fluid and electrolyte homeostasis • Perioperative fluid loss: blood, intravascular fluid loss, insensible losses • After surgery : effusions and drainage. • artificial ventilation of the intubated patient : the normal mechanisms for humidifying gases are bypassed.  considerable amount of fluid can be lost • extravasation of fluid out of the vascular compartment (the 'third space effect').

Perioperative fluid requirements • Intraoperatively: according to the extent surgery - minimal trauma 4 ml/kg/h - moderate trauma 6-8 ml/kg/h - severe trauma 10-15 ml/kg/h : best provided as Compound Sodium Lactate or other balanced salt solutions  as large NS: hyperchloraemic metabolic acidosis • postoperative period : the standard daily needs for a 70 kg adult - 100 ml/h - 25-33% normal saline, 75-66% dextrose (=water) - 10-20 mmol KCl per litre of fluid.

Aetiology of postoperative renal dysfunction • multi-factorial : the commonest cause is ATN  hypotension, hypovolaemia, dehydration. • common associated risk factors - preexisting renal insufficiency, - type 1 DM, - patient age over 65 yr, - major vascular surgery, - cardiopulmonary bypass times over 3 h, - recent exposure to nephrotoxic agents: radio-contrast dyes, bile pigments, aminoglycosides, NSAIDs)

Preoperative : - arteriopaths(reduced renal perfusion) - age-related decline in nephron mass - pre-existing renal dysfunction • Intraoperative - Hypovolaemia - Nephrotoxins : contrast media - Embolism - Renal ischaemia : ACEI therapy - Inflammation - Genetic predisposition : apoE gene

Incidence of postoperative renal dysfunction • Three useful criteria - increase of serum Cr. by more than 44 µmol/litre (>0.5 mg/dl) - increase > 50% - more than 177 µmol/litre • varies according to the aetiology and definition, and type of surgery undergone : 4-24% • renal failure is associated with mortality rates of 60-90% • postoperative ARF is accompanied : increased ICU stay, hospital stay, gastrointestinal bleeding, respiratory infections, sepsis

In CABG on cardiopulmonary bypass : 1 - 15%  associated with a mortality of 19% : requiring dialysis is less than 2%  mortality 23 - 88% (average about 50%) • Why ARF occur after CABG : the combination of low C.O and hypovolaemia • Gamoso and colleagues : renal dysfunction rates undergoing cardiac surgery : under bypass (7.7%) : off-pump (8.9%)  Recent data suggest that off-pump cardiac surgery may better preserve renal function

Suprarenal aortic cross-clamping : dialysis requiring ARF of 5.5%  in-hospital mortality of 63%. : important predictors of ARF pre-existing renal dysfunction evidence of diffuse atherosclerosis use of intraoperative pump bypass haemodynamic instability • Infra-renal aortic cross-clamping : 5.4%, but only 0.6% received dialysis : 69% mortality in renal failure and required dialysis

Surgery for relief of obstructive jaundice - renal dysfunction : up to 60% - associated with a significant mortality(68%) - causative factors : hyperbilirubinaemia increased serum level of bile salts endotoxaemia, renovascular fibrin deposition altered systemic and renal haemodynamics.

Prevention of renal dysfunction and renal protection • Most current practices used to renal protection : tradition, anecdotal information, animal models • logic suggests : maintain a urine flow 0.5 ml/kg/h • commonly used approaches to prevent ARF : adequate hydration, mannitol, dopamine(renal doses), loop diuretics.

Sequelae of postoperative renal dysfunction • abnormal GFR vs adverse drug reactions  prolongation of half-life of drugs, metabolites changes in bioavailability changes in volumes of drug distribution changes in plasma protein binding • preoperative risk factors predictive of ARF - preoperative renal dysfunction, - advanced age, - cardiac dysfunction

Conclusions • postoperative renal impairment : major cause of perioperative morbidity and mortality. • Surgery type being undertaken is important, as is the presence of preexisting renal dysfunction. • Although a number of preventative strategies have been described, none apart from maintenance of normovolaemia appears to be effective.

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