BY DR/ WASEEM Z. AZIZ LECTURER OF ANAESTHESIA AND INTENSIVE CARE AIN SHAMS UNIVERSITY MARCH 2009
QUESTIONS 1. The risk of development of acute renal failure after cardiac surgery is highest in: a. Neonates. b. Infants. c. Children. d. Adults.
QUESTIONS 2. Which of the following causes vasodilation of the cortical vasculature? a. Mannitol. c. Both. b. Furosemide. d. Neither.
QUESTIONS 3. Clinical settings in which mannitol has definitely been shown to be effective in preventing the deterioration of renal function is: a. During and after cardiopulmonary bypass. b. During and after aortic cross-clamping. c. During and after hypovolemic shock. d. Before the administration of cisplatin. e. None of the above.
QUESTIONS 4. Which of the following statements is least accurate regarding acute renal failure? a. Adults with no underlying renal disease who develop acute renal failure have a worse prognosis compared with children. b. Following cardiac surgery, the incidence of acute renal failure is higher in children than in adults. c. Children over the age of 2 years with acute renal failure have a much better outlook with meticulous medical care. d. Spontaneous recovery from acute renal failure is likely to begin 1–3 weeks after onset. e. The mortality rate for children with acute renal failure is much higher than in adults
QUESTIONS 5. Which of the following statements is true regarding management of suspected acute renal failure? a. In euvolemic patients, the rapid intravenous administration of mannitol should result in a urine output greater than 0.5 mL/kg within 1 hour if a prerenal etiology dominates. b. The vasodilatory and natriuretic properties of furosemide are beneficial when administered early in the course of acute renal failure. c. In euvolemic patients, furosemide in an incremental dose of up to 10 mg/kg may be used. d. If there is no response to a fluid challenge, low dose dopamine could be added. e. All of the above
QUESTIONS 6. In a patient who has just been admitted to the pediatric intensive care unit with new onset of acute renal failure, which of the following pathophysiological changes is least likely to occur? a. Blood urea nitrogen (BUN) and creatinine will rise at 10 and 0.5 mg/dL/day, respectively. b. Serum HCO3 decreases by 2 mEq/L/day because of release of tissue phosphate. c. Serum K+ increases by 0.3–0.5 mEq/L/day. d. Hypernatremia is commonly observed. e. Hypophosphatemia and associated hypocalcemia may develop rapidly after the onset of acute renal failure
Incidence of postoperative renal dysfunction Postop. renal failure (more in pediatrics) is associated with mortality rates of 60–90% (more in adults than pediatrics). The incidence of renal impairment varies between 4 and 24% because there is no rigid definition of renal dysfunction. In cardiac surgery Postoperative ARF sepsis ↑ ICU stay ↑ length of ↑ GI ↑ requiring hospital stay bleeding infection
RENAL PHYSIOLOGY RBF = 20% of resting CO ↓ by atherosclerosis ↓ CO α- adrenergic ++ (↓ RBF inspite of maintain BP) Intraglomerular blood pressure =the difference between the pressures in the efferent and afferent arterioles) GFR=100-200ml/min
RENAL PHYSIOLOGY GFR autoregulated across wide range of ABP but urine output is not. ( UOP with arterial BP. e.g 100mmHg 200 7 times ↑ in UOP ˂ 50mmHg stop of UOP due to slight rise in GFR but ↑ peritubular vascular pr. ↓ reabsorption of filterate. Linear ↑
RENAL PHYSIOLOGY RBF=20% of CO ≈50 ml/min→ O 2 delivery≈50ml/min/100gm tissue Distribution is not uniform→≈90% to cortex O 2 utilization only 10% low A-V O 2 content of total body utilization difference in kidney adequate oxygen reserve ?? Why kidney is highly sensitive to hypoperfusion?? ?? Why ARF is frequent complication of hypotension? PARADOX???
Due to physiological gradient of intra-renal oxygenation with the renal medulla able to function at ambient oxygen tensions of 2–3 Kpa This low oxygen tension results from the high oxygen requirement for tubular reabsorptive activity of sodium and chloride. Although a high percentage of the medullary region has a blood goes to cortex far smaller blood flow NEED only about 18% of total about 79% of the delivered oxygen oxygen delivered to it (heterogeneity of flow and oxygen requirement)
MEDULLA More susiptable to hypoxic injury→ ATN esp in thick ascending limb (mTAL) ATN occurs by ↓ 40-50% of RBF Loop diuretics protects (if any) by ↓o2 dependent reabsorption of mTAL → ↓o2 requirement Needs strict control
MEDIATORS AFFECT MEDULLARY BLOOD FLOWVasodilators NO PGE 2 Adenosine Dopamine Urodilatin (ANP analogue) VASOCONSTRICTORS ET Angiotensin II ADH Tubulo-glomerular feedback insulin-like growth factor I epidermal growth factor tumour necrosis factor
PHARMACOLOGICAL CONTROL OF RBF kidney is largely devoid of β2 receptors ++ α 1 so CA ++ renin angiotensin system So, ischemia→ ++ CA→ renal cortical VC try to redistribute blood flow to the renal medulla
THE IMMATURE KIDNEY Children undergoing heart surgery are more vulnerable to postoperative renal dysfunction relative to adults Normal full term 1-3 y ↓ Full renal fun of adults Few weeks→ gain most fun = Acidification of urine At birth: anatomic growth of 1 million nephrons 3 rd trimester→ urine = amniotic fluid = 1cup/hr Preterm Depends on conceptional age Delay to retain normal kidney function
The Problematic Definition of Acute Kidney injury(AKI) The Conceptual Definition of Acute Kidney injury (instead of ARF): “Sudden loss of renal function resulting in the loss of the kidneys’ ability to regulate electrolyte and fluid homeostasis”
The Problematic Definition of Acute Kidney injury(AKI) Pediatric AKI definition: a moving target Infants Cr in the first few weeks of life may reflect maternal values Children Low baseline Cr makes 0.2-0.3 changes in Cr significant Varying muscle mass Adolescents Similar to adults
The Problematic Definition of Acute Kidney injury(AKI) Over 30 published ARF definitions All based on increased serum creatinine levels Despite extensive adult hospitalized patient study over the past 50 years Widely varying spectrum dependent upon study aims and hypothesis Severe (ARF requiring dialysis) Modest (serum creatinine increase of 0.3 mg/dl)
The Problematic Definition of Acute Kidney injury(AKI) Diagnostic criteria for acute kidney injury http://ccforum.com/content/11/2/R31 An abrupt (within 48 hours) reduction in kidney function currently defined as an absolute increase in serum creatinine of more than or equal to 0.3 mg/dl (≥ 26.4 μmol/l), a percentage increase in serum creatinine of more than or equal to 50% (1.5-fold from baseline), or a reduction in urine output (documented oliguria of less than 0.5 ml/kg per hour for more than six hours). NB: - 2 cr levels within 48hrs. - adequate hydration - variation of serum creatinine with modern analyzers is relatively small and therefore increments of 0.3 mg/dl (25 μmol/l) are unlikely to be due to assay variation
Classification/staging system for acute kidney injury RIFLE MODIFIED
RIFLE classification of AKI http://ccforum.com/content/11/2/R31
Modified from RIFLE Urine output criteriaSerum creatinine criteriaStage Less than 0.5 ml/kg per hour for more than 6 hours Increase in serum creatinine of more than or equal to 0.3 mg/dl (≥ 26.4 μmol/l) or increase to more than or equal to 150% to 200% (1.5- to 2-fold) from baseline 1 Less than 0.5 ml/kg per hour for more than 12 hours Increase in serum creatinine to more than 200% to 300% (> 2- to 3-fold) from baseline 2 Less than 0.3 ml/kg per hour for 24 hours or anuria for 12 hours Increase in serum creatinine to more than 300% (> 3-fold) from baseline (or serum creatinine of more than or equal to 4.0 mg/dl [≥ 354 μmol/l] with an acute increase of at least 0.5 mg/dl [44 μmol/l]) 3 http://ccforum.com/content/11/2/R31
Difference between two classifications Up to 1 wk Stages 3,4,5 5 stages RIFLE Cr changes Difference Within 48hs Stage 3 only Renal replacement therapy 1→Risk in RIFLE 2,3→Injury and Failure No 4,5 as being chronic staging Modified AKI
Aetiology of postoperative renal dysfunction Risk Factors (In General) PREOPERATIVE ARTERIOPATHY Pre-existing renal disease. IDDM Age ˃ 65ys or ˂ 2ys Major vascular disease. INTRAOPERATIVE 1.Hypovolemia→ neurohormonal effects Sympatho- aldosterone adrenal ADH Angiotensin glucocortcoids VC 2. nephrotoxins:→intrarenal VC →↑ osmotic load
3. Renal ischemia: by concurrent use of ACEI 4.Inflammation: gut ischemia→ endotoxemia→ cytokines 5.Genetic predisposition: certain gene deletion →↑% of inflamm. response. →↑ IL6, IL10→↑% of renal dysfunction this deletion is more with same congenital heart disease
The etiology of renal dysfunction in cardiac surgery PostoperativeIntraoperativePreoperative Systemic inflammation Decreased renal perfusion Lack of renal reserve Reduced LV function hypotensionRenovascular disease Vasoactive agents lack of pulsatile flow Prerenal azotemia Hemodynamic instabilityVasoactive agentsrecent diuresis Nephrotoxinsanesthetic effectsNPO status Volume depletionEmbolic eventsimpaired LV function Sepsis CPB-induced inflammation ACEI/ARB Nephrotoxins free hemoglobinintravenous contrast other medications Endotoxemia Inflammation
More Risk in children Immature kidney More dependent of renin angiotensin system for perfusion. Risk factors are as adults + Neonatal age group Cyanotic heart disease CPB duration Low CO Perioperative hypotension
In cyanotic heart disease 1.Still most imp risk factor is low CO. 2.Associated pre existing renal anomalies: eg. Trisomy 21 (down syn) Trisomy 18 (Edward syn) Trisomy 13 (Patau syn) VATER association 22q11 microdeletion 3.chronically→ cyanotic ht dis → chronic hypoxia 3 stages ectasia of glomerullar capillaries→benign proteinurea (early sign 5 ys age of renal dysfunction) mesangial proliferation with destruction changes of capillary wall 2 nd decade glomerular sclerosis
WHAT TO DO? EARLY IDENTIFICATION EARLY RENAL INJURY PREVENTIVE (MARKERS) MEASUERS
IDENTIFICATION OF RENAL INJURY Renal function tests available for clinical use Urine volumeUrine specific gravityUrine osmolality Serum creatinine and blood urea nitrogen Urine/plasma creatinine ratio Urine/plasma urea ratio Urinary sodium excretion Fractional excretion of sodium Free water clearance Creatinine clearance Renal blood flow
IDENTIFICATION OF RENAL INJURY Classic methods Serum creatinine Easy measurement Proportional to GFR in steady state (not in acute injury) Affected by GFR in addition to tubular secretion, generation and elimination of creatinine. Varies with intravascular volume muscle mass, age, and sex, and it is affected by muscle trauma, fever, liver disease, and immobilization. 50% of the function of the kidney can be lost without an increase in sCr. Change with age. eg. sCr of 1.5 mg/dL corresponded to a GFR of approximately 77 mL/min in a 20 year-old black male, it corresponded to merely 36 mL/min in a 80 year-old white female.
CASE A 10-day-old male infant weighing 950 g was scheduled for ligation of patent ductus arteriosus (PDA). He was born at 29 weeks gestation and was intubated immediately after delivery because of respiratory distress. His condition improved over the following 4 days. However, on the fifth day of his life the respiratory distress worsened and a murmur was heard over his chest. Medical treatment for PDA was attempted unsuccessfully. His blood pressure was 60/40 mm Hg, heart rate 150 beats/minute. The laboratory data were as follows: white blood cells (WBCs), 17,000/L; hemoglobin, 11 g/dL; hematocrit, 34%; urine specific gravity, 1.005; protein 1+; sugar 1+; serum calcium 6.0 mg/dL; blood glucose 60mg/dl, S creatinine 1.6mg/dl ; and arterial blood gases: pH, 7.30; PaCO 2, 45 mm Hg, PaO 2, 60 mm Hg on FIO 2 50%; inspiratory pressure, 30/4 cm H 2 O; and ventilation rate, 25 breaths/minute.
The creatinine levels of term infants at birth are 0.6 to 1.2 mg/dL, but within 1 month fall to levels of 0.1 to 0.2 mg/dL. Preterm infants have relatively high serum creatinine levels compared with term infants. They are 0.8 to 1.8 mg/dL at birth and fall to 0.2 to 0.8 mg/dL in 1 month. The normal BUN level is 10 to 20 mg/dL in term infants, whereas it is 16 to 28 mg/dL in preterm infants. In infants weighing 1,000 to 3,300 g, the normal urine-specific gravity is 1.005 to 1.010. A urine specific gravity of more than 1.020 suggests dehydration. Glucosuria 1+ normally presents in 13% of preterm infants who are less than 34 weeks gestational age because the preterm infant has a decreased renal tubular reabsorption for glucose. After 34 weeks of gestational age, glucosuria is usually associated with hyperglycemia. Albumin is normally filtered by the glomerulus and is completely reabsorbed. However, because of tubular immaturity, 16% to 21% of preterm infants have proteinuria.
IDENTIFICATION OF RENAL INJURY Classic methods Creatinine clearance (ClCr) = (urine Cr × urine volume)/ serum creatinine ≈ GFR Cockcroft-Gault formula: CrCl = ([140 - age] X weight)/(72 X Scr) (multiplied by 0.85 if female sex) overestimates GFR because tubular secretion of creatinine is ignored FENa is another measure to assess kidney function FEs =(Us × V) / Ps FE =the fractional excretion, s =any substance GFR Us =the urinary concentration of the substance Ps = the plasma concentration, and V =the urine flow rate. renal failure index (RFI) = UNa Ucr/PCr Both RFI and FENa diff. bet renal and prerenal impairment Also modified by diuretics
IDENTIFICATION OF RENAL INJURY BIOMARKERS Are urinary kidney-specific proteins. Ideally AKI would have a biomarkers like myocardial infarction (i.e. troponin-1) Currently no Troponin-I like marker to identify the site or severity of injury, although various markers are being evaluated
BIOMARKERS URINARY ENZYMES NAG AP Ϫ GT α GST π GST URINARY LOW MOLECULAR PROTEINS Α1 microglobulin β2 microglobulin Cystatin C NHE 3 NGAL KIM 1
IDENTIFICATION OF RENAL INJURY BIOMARKERS Current status of promising acute kidney injury (AKI) biomarkers in various clinical situations
IDENTIFICATION OF RENAL INJURY BIOMARKERS Example : Cystatin C Cysteine proteinase inhibitor. Not depend on muscle mass, sex, and age Not affected by inflammation, fever, and extrinsic substances Allow earlier detection of renal impairment than sCr.
KIDNEY-SPECIFIC PROTEINS AND CARDIAC SURGERY all original studies from 1990 to 2005 in which kidney-specific proteins were measured in patients undergoing cardiac surgery were reviewed…………..but: Mostly are observational studies. Small no. of patients. Pt population are wide ( off- and on-pump surgery, CABG surgery, valve surgery, and even children with correction of congenital heart disease). The period of studying varied from 1 hour to 40 days after surgery. The conventional measures for detecting kidney injury varied widely; some used CrCl, others used sCr or UOP. No common definition for AKI. No long term kidney function followup. So we need more specific studies
Prevention of renal dysfunction and renal protection in cardiac surgery The superior doctor prevents sickness; The mediocre doctor attends to impending sickness; The inferior doctor treats actual sickness; Chinese proverb
Strategies of Renal Protection 1. Maintain adequate oxygen delivery—by ensuring adequate cardiac output, adequate oxygen carrying capacity, and proper haemoglobin saturation. 2. Suppression of renovascular constriction—by ensuring adequate volume preload, use of infusions of mannitol, calcium entry block, and angiotensin converting enzyme inhibitors. 3. Renal vasodilation—by dopaminergic agents, prostaglandins, and atrial natriuretic peptide. 4. Maintain renal tubular flow—by loop diuretics and mannitol (which may act to prevent tubular obstruction which can cause cellular swelling, ischaemia and death). 5. Decrease oxygen demand—by use of loop diuretics and mild cooling. 6. Attenuate ischaemic reperfusion injury—as a result of the release of oxygen free radicals and calcium ions.
Prevention of renal dysfunction and renal protection in cardiac surgery Prevention of AKI Strategies for renal protection Enhancement of DO2 Suppression of reflex V.C. Pharmacological renal V.D. Maintance of tubular flow Decrease VO 2 Adequate hydration Pharmacological intervention Dopamine Dopexamine Fenaldopam ACEIs & ARBs diuretics ANP N- Acetylcysteine Theophylline Cardiac glycosides Ca +2 Channel blockers Corticosteroids Insulin Endothelin antagonist PGs NO CPB hemodilution hypothermia Pulsatile perfusion Oxygenators And filters
HYDRATION Studies for crystalloids vs colloids (no difference) Type: ?? NS, LR,…….Hetastarch,albumin… Amount:??controversy Target CVP of at least 14-16mmHg Fill till signs of overfill just manifest o CVP>16mmHg o Drop in PO 2 /FO 2 ratio o Bilateral crackles o S3 o Loss of stroke volume variation
PREVENTION CPB Why CPB is risky? Inflammatory response during bypass Increased vasoconstriction (due to ↑ ET) Reduced blood flow in capillaries Endothelial dysfunction Evidence of vascular obstruction and congestion up-regulation of adhesion molecules, with increased levels of ET1, which promotes adhesion A reduction in nitric oxide production (which inhibits adhesion) postbypass Ischemic reperfusion injury + low CO & hypovolemia Associated hypoxia and hypotension
Inflammation in CPB STIMULI ( surgical trauma, blood contact with CPB surface, Endotoxemia, Ischemia, Hb) MEDIATORS Complement:C3a,C5a Cytokines:IL1,2,6,8,10, TNFα O2 free radicals Effects Leucocyte extravasation Lipid perioxidation Edema Cell death ACUTE KIDNEY INJURY Transcription Factor (NF- κ B (nuclear factor kappa- light-chain-enhancer of activated B cells) Adhesion Molecules E,P,L selectin Integrin CD8/CD11 Ig superfamily: ICAM,VCAM
Glomerulus from group A anesthetized and heparinized only. Well-filled capillaries with clear definition of glomerular anatomy. AA afferent arteriole; EA efferent arteriole; GC glomerular capillaries; PD polar diameter PATHI ET AL RENAL MICROCIRCULATION AND CARDIOPULMONARY BYPASS Ann Thorac Surg1998;65:993–8
Glomerulus from group B (cardiopulmonary bypass at 28°C, for 30 minutes) Smaller glomerulus with narrowed capillaries suggesting diversion of flow through alternative channels PATHI ET AL RENAL MICROCIRCULATION AND CARDIOPULMONARY BYPASS Ann Thorac Surg1998;65:993–8
Glomerulus from group C (cardiopulmonary bypass at 28°C, for 120 minutes) Severe reduction in size of glomerulus with complete loss of functional unit. These act as shunts between afferent and efferent arteriolar systems PATHI ET AL RENAL MICROCIRCULATION AND CARDIOPULMONARY BYPASS Ann Thorac Surg1998;65:993–8
Glomerulus from group D (cardiopulmonary bypass at 28°C, 120 minutes; an 30 minutes of normothermic perfusion at the end) Some recovery of anatomy of the functional unit, although shunting of blood past the nephrons is still evident. Narrowing of the capillaries and increase in intercapillary spaces suggest interstitial edema PATHI ET AL RENAL MICROCIRCULATION AND CARDIOPULMONARY BYPASS Ann Thorac Surg1998;65:993–8
CARDIOPULMONARY BYPASS PROCEDURAL FACTORS clinically, although there are multiple experimental and clinical studies suggesting that various procedural aspects of CPB may be detrimental to the kidney, there is no clear consensus that CPB per se causes renal failure. ?? PROTECTIVE + PROTECTIVE HEMODILUTIONHYPOTHERMIA OXYGENATORS AND FILTERS PULSATILE PERFUSION
HEMODILUTION 2 opposing effects As O 2 carrying capacity α HCT Hemodilution ↓ afterload ↓ viscosity Hemodilution ↑ CO ↑ bl. flow in ↓RBCs oxygenation microcirculation at postcapillary ↓ O 2 transport venules ↑ O 2 Delivery the net effect is ↑ O 2 delivery
HEMODILUTION From the figure: the most suitable Hct is 28-30% blood priming for pediatric population Hint H. The pharmacology of dextran and the physiological background for the clinical use of Rheomacrodex and Macrodex. Acta Anaesth Belg 1968;19:119–138
HYPOTHERMIA ↓ metabolic rate ↑ intracellular PH ?? Controversy about: Warm cardioplegia Warm Ht surgery ( normothermic bypass) But studies→ less evidence of protective effects of hypothermia on kidneys.
PULSATILE PERFUSION More physiologic Improve microcirculation But no evidence that is superior to non pulsatile perfusion in renal protection.
OXYGENATORS AND FILTERS o When bubble oxygenators was used → multiple emboli was found in brain, heart and kidneys → less with membrane oxygenators and arterial filters. o But in pediatric units → only 30% of centers use filters because large amount of volume required to prime the filters.
PREVENTION DRUG THERAPY basic ANPACEIDopaminedopexamine Loop diuretics CCBmannitol Others ET antagonists PGE1fenoldopamclonidinedexamethasonepentoxyifyllineN-acetylcysteine A single-chain antibody specific for human (C5 (pexelizumab
DOPAMINE ↓ Activity of Na + /K + ATPase. Renal V.D.(D 1 receptors in low dose 0.5-2.5 µg/Kg/min). ↑ CO (β 1 receptors ˃ 5-10 µg/Kg/min). Studies → controversy → ?? Diuretic → ++ ↑ CO
DOPEXAMINE Sympathomimetic agent. Mainly on β 2 agonist→ +ve inotropic +ve chronotopic ??↓ vascular resistance In animals (not in human)→DA 1 agonist →↑ renal bl. flow→ diuresis But human→ diuresis only by ↑ CO.
LOOP DIURETICS FUROSEMIDE Renal V.D. ?? Dose: 0.5mg/kg/min. for 48hrs ?? Effective prophylaxis (only pigment nephropathy) High-dose furosemide has been shown to decrease the duration of oliguria and need for dialysis in patients with ARF, but has no effect on mortality.
Calcium Channel Blockers eg: verapamil, diltiazim Mech:↑cytoplasmic Ca + blocked arteriolar vc by CCB
ACE I Pretreatment with ACEI→↓ the increase of renal vascular resistance associated with cross clamping. But →?? May ↑ postop. Renal dysfunction
Atrial Natriuretic peptide (ANP) (Urodilatin) ANP produced due to stretch by volume overload VD of afferent arterioles. ↑GFR VC of efferent arterioles. Anaritide, a synthetic analogue of ANP, there was improved mortality in treated patients with oliguria. administration of urodilatin (a natriuretic peptide found in human urine) is beneficial in oliguric patients after cardiac surgery and significantly reduces mortality and the need for dialysis. In comparison with circulating ANP, urodilatin exerts greater diuretic properties. Its method of action is thought to involve both improving renal blood flow and acting upon the distal collecting system
OTHER POSSIBLE THEREAPIES 1-ET Antagonist ET 1 → V.C We need either→ ET receptor antagonist OR→ ET antibodies 2- Prostaglandins E 1 Endogenous renal V.D
3-DOPAMINERGIC DRUGS FENOLDOPAM Selective DA 1 agonist. Introduced mainly as an antihypertensive agent. It ↓ blood pressure in a dose-dependent manner while preserving RBF and GFR. Dose: 0.03-0.05 ng/kg/min
3-FENOLDOPAM Mech 1 : DA 1 agonist→VD→↑ RBF. No effect on myocardial contractility as dopamine(no β effect)→ less arrhythmogenic and no tachycardia. Mech 2 : -- of Na + transport in the mTAL region →↓ O 2 utilization.
3-FENOLDOPAM " When we looked at the results, there was no difference between the fenoldopam group and those treated with standard therapy," says Landoni (Continuous Improvement in Cardiac Surgery Program )(CICPS). End point Fenoldopam, n (%) Dopamine, n (%)p Acute renal failure (25% increase in serum creatinine from baseline) 17 (42.5)16 (40)0.9 Renal replacement therapy 4 (10) 0.9 Death4 (10)3 (7.5)0.5 Bove T et al Circulation 2005; 111:3230-3235
Continuous Improvement in Cardiac Surgery Program (CICPS) concluded that at high risk patients (eg. CABG) ARF depends on factors linked to poor cardiac performance and advanced atherosclerotic vascular disease not to vasodilatory effects so, in pediatric population need more studies
4-CLONIDINE α-adrenergic ( α 1 and α 2 ) agoniost. Mech: inhibits ADH production (central α 1 effect). Inhibits reabsorption of Na and H 2 O ( peripheral α 2 effect). block adrenergic VC stimuli to surgical stress →↓ renal hypoperfusion. Dose: 4µg/kg
5-PENTOXIFYLLINE o PDE Inhibitor→-- activation of neutrophil by TNFα and IL-1, and TNF-α release by inflammatory cells. o No direct effect on kidneys. 6-STEROIDS (DEXAMETHASONE) o failed to protect against renal dysfunction after cardiac surgery. o A recent study examined the effect of blocking complement activation in patients who underwent CPB
7- A single-chain antibody specific for human C 5 (pexelizumab) C 5 → block complement activation→ ??renal function after CPB 8- N-acetylcysteine (N-AC) o block inflammation and oxidant stress in cardiac surgery patients. o studied most extensively in the prevention of radiocontrast induced nephropathy.
SUMMARY Renal failure is relative rare complication but associated with a 10-fold increase in surgical mortality. Although CPB is a nonphysiologic state that alters renal blood flow and many neuroendocrine responses affecting the kidney, there is little clear- cut evidence that CPB per se is responsible for renal dysfunction. Risk factors mainly:→perop→renal dysfunc →intraop→infammatory response →postop→↓ COP Protection mainly to maximize postop. COP to avoid renal hypoperfusion.
Principles of management of oliguria and acute renal failure Assess hydration and circulation volume. Urinary bladder palpable? Clinical examination Place a urinary cath. Measure UOP accurately Urinary and plasma electrolytes, urea, creatinine and osmolarity. Calculate FE Na Calculate U: P ratios for Na +, urea and osmolarity. Biochemistry Withholding potentially toxic drugs (eg vancomycin, aminoglycosides,...) Myoglobin(hyperpyrexia) Hemoglobin(hemolysis) Initiate specific therapy if appropriate Nephrotoxins Normalize circulating volume and cardiac output Optimize treatment of heart failure. Circulation Pattern of renal arterial and venous blood flow (renal artery or vein thrombosis) Appearance of kidneys. Rule out potential obstruction. Renal ultrasound Initially restrict fluid intake to 30% of normal requirement + UOP Renal replacement therapy may be necessary if therapeutic or metabolic demand can not be met within these fluids limits. Fluid management Frequent measurements of plasma biochemistry Danger of hyperkalemia Rapid rise of urea/creatinine may determine early use of renal replacement therapy Metabolic management Furosemide Mannitol Hyperkalemic management Drug therapies to decrease injuries and promote recovery Peritoneal dialysis Hemofilteration Hemodialysis Renal replacement therapy
SPECIAL SITUATION AORTIC SURGERY Paraplegia and renal failure are the main determinants in postoperative mortalities. In pediatrics eg. Coarctation, aneurysm (Marfan,..)...... Problem: Aortic cross clamp (suprarenal vs infrarenal) renal protection including: Hypothermic CPB with circulatory arrest. Selective volume and pressure controlled perfusion by: Retrograde aortic perfusion,followed by o warm blood visceral perfusion, o Cold crystalloids renal arteries perfusion o antegrade cold blood visceral perfusion, o retrograde cold blood perfusion, and o the perioperative use of a renal protective pharmacologic agent, fenoldopam. Perform selective perfusion by 4 branched tubing system connected to extracorporeal circulation with the 4 braches connected to celiac, superior mesenteric and 2 renal arteries. Shunts o both temporary and permanent. o These included permanent axillo-bifemoral graft, aorto iliac Gott shunt, axillo-femoral Gott shunt, temporary axillofemoral graft, combination of double clamping then temporary perfusion using a Javid shunt. o These techniques have the disadvantages of complexity or of incurring significant period of renal ischaemia.
ASWERS 1. The risk of development of acute renal failure after cardiac surgery is highest in: a. Neonates. b. Infants. c. Children. d. Adults.
1.A Kidneys are able to maintain renal blood flow over a wide range of systemic blood pressures by autoregulation of intrarenal vascular resistance. Therefore, hypotension with renal hypoperfusion may or may not produce ischemic renal injury. However, these autoregulatory mechanisms are not well developed in neonates. Neonates have high renin levels, which in turn, are associated with decreased glomerular filtration rate (GFR) and reduced outer cortical blood flow. The cortical glomeruli are immature and so are their corresponding tubules. This pattern of high renin and reduced outer cortical blood flow makes neonates more vulnerable to renal dysfunction as a result of hypotension of systemic pressures only slightly below the normal range. In animal studies, newborn animals have decreased production of atrial natriuretic peptide in response to saline challenge. All these factors combined make the incidence of acute renal failure in neonates, after cardiac surgery, higher than in older infants and children. (Nichols DG, et al. Critical Heart Disease in Infants and Children, Mosby 1995; pp. 125, 562.)
2. Which of the following causes vasodilation of the cortical vasculature? a. Mannitol. c. Both. b. Furosemide. d. Neither.
2. C Furosemide causes vasodilation of the cortical vasculature by direct action and through release of prostaglandins. Furosemide maintains renal blood flow and tubular blood flow when cardiac output is compromised. Mannitol is also a vasodilator of the cortical vasculature that increases renal blood flow either directly by drawing fluid from extravascular to intravascular space, thus increasing total plasma volume, or by increasing prostaglandin production. Increased plasma volume alone does not fully explain the effects of mannitol, because volume expansion with saline improves renal blood flow without improving GFR. The improvement in GFR seen with mannitol is associated with a decrease in afferent and efferent arteriolar resistance, which is probably mediated by prostaglandins. (Rogers MC, et al. Textbook of Pediatric Intensive Care, 2nd Edition; pp. 1192–1194, 1202.)
3. Clinical settings in which mannitol has definitely been shown to be effective in preventing the deterioration of renal function is: a. During and after cardiopulmonary bypass. b. During and after aortic cross-clamping. c. During and after hypovolemic shock. d. Before the administration of cisplatin. e. None of the above.
3. D Clinical studies comparing prophylactic administration of mannitol (or furosemide) with maintenance of adequate intravascular volume during cardiopulmonary bypass failed to reduce the incidence of postoperative renal dysfunction. However, there are experimental studies that have shown some beneficial effects of mannitol. Mannitol has been shown to be effective in preventing deterioration of renal function before administration of Amphotericin B and Cis- Platinum. (Rogers MC, et al. Textbook of Pediatric Intensive Care, 2nd Edition; pp. 1194,1195; Nichols DG. Critical Heart Disease in Infants and Children, Mosby 1995; pp. 129,130; Olivero JJ, et al. Br Med J, 1975; 1:550; Hayes D, et al. Cancer, 1977; 39:1372.)
4. Which of the following statements is least accurate regarding acute renal failure? a. Adults with no underlying renal disease who develop acute renal failure have a worse prognosis compared with children. b. Following cardiac surgery, the incidence of acute renal failure is higher in children than in adults. c. Children over the age of 2 years with acute renal failure have a much better outlook with meticulous medical care. d. Spontaneous recovery from acute renal failure is likely to begin 1–3 weeks after onset. e. The mortality rate for children with acute renal failure is much higher than in adults
4. E Children have a lower mortality compared with adults. (Rogers MC, et al. Textbook of Pediatric Intensive Care, 2nd Edition; pp. 1198–1201.)
5. Which of the following statements is true regarding management of suspected acute renal failure? a. In euvolemic patients, the rapid intravenous administration of mannitol should result in a urine output greater than 0.5 mL/kg within 1 hour if a prerenal etiology dominates. b. The vasodilatory and natriuretic properties of furosemide are beneficial when administered early in the course of acute renal failure. c. In euvolemic patients, furosemide in an incremental dose of up to 10 mg/kg may be used. d. If there is no response to a fluid challenge, low dose dopamine could be added. e. All of the above
6. In a patient who has just been admitted to the pediatric intensive care unit with new onset of acute renal failure, which of the following pathophysiological changes is least likely to occur? a. Blood urea nitrogen (BUN) and creatinine will rise at 10 and 0.5 mg/dL/day, respectively. b. Serum HCO3 decreases by 2 mEq/L/day because of release of tissue phosphate. c. Serum K+ increases by 0.3–0.5 mEq/L/day. d. Hypernatremia is commonly observed. e. Hypophosphatemia and associated hypocalcemia may develop rapidly after the onset of acute renal failure
5-6. E, D All of the strategies mentioned are appropriate for oliguria in a setting of suspected renal insufficiency. With the onset of acute renal failure, hyponatremia is more commonly seen owing to the dilutional effect of intake of fluid orally, which is mostly hypotonic. (Rogers MC, et al. Textbook of Pediatric Intensive Care, 2nd Edition; p. 1202. Nichols DG. Critical Heart Disease in Infants and Children, Mosby 1995; pp. 128–138.)