RENAL PROTECTION IN PEDIATRIC CARDIAC SURGERY 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 prerenaletiology 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 Linear ↑ • 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.
RENAL PHYSIOLOGY RBF=20% of CO ≈50 ml/min→ O2 delivery≈50ml/min/100gm tissue Distribution is not uniform→≈90% to cortex O2 utilization only 10% low A-V O2 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)
PHARMACOLOGICAL CONTROL OF RBF kidney is largely devoid of β2 receptors ++ α1 so CA ++ reninangiotensin system So, ischemia→ ++ CA→ renal cortical VC try to redistribute blood flow to the renal medulla
THE IMMATURE KIDNEYChildren undergoing heart surgery are more vulnerable to postoperative renal dysfunction relative to adults
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 http://ccforum.com/content/11/2/R31
Aetiology of postoperative renal dysfunctionRisk Factors (In General) PREOPERATIVE ARTERIOPATHY • Pre-existing renal disease. • IDDM • Age ˃65ys or ˂2ys • Major vascular disease. INTRAOPERATIVE • 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
More Risk in children • Immature kidney • More dependent of reninangiotensin system for perfusion. • Risk factors are as adults + • Neonatal age group • Cyanotic heart disease • CPB duration • Low CO • Perioperative hypotension
In cyanotic heart disease • Still most imp risk factor is low CO. • Associated pre existing renal anomalies: eg. • Trisomy 21 (down syn) • Trisomy 18 (Edward syn) • Trisomy 13 (Patausyn) • VATER association • 22q11 microdeletion • chronically→ cyanotic ht dis → chronic hypoxia 3 stages ectasia of glomerullarcapillaries→benignproteinurea (early sign 5 ys age of renal dysfunction) mesangial proliferation with destruction changes of capillary wall 2nd 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
IDENTIFICATION OF RENAL INJURYClassic 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 ductusarteriosus (PDA). He was born at 29 weeks gestation and was intubatedimmediately 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; PaCO2, 45 mm Hg, PaO2, 60 mm Hg on FIO2 50%; inspiratory pressure, 30/4 cm H2O; 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 INJURYClassic 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 INJURYBIOMARKERS • 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
IDENTIFICATION OF RENAL INJURYBIOMARKERS Current status of promising acute kidney injury (AKI) biomarkers in various clinical situations
IDENTIFICATION OF RENAL INJURYBIOMARKERS Example : Cystatin C • Cysteineproteinase 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 atrialnatriuretic 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
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 • CVP>16mmHg • Drop in PO2/FO2 ratio • Bilateral crackles • S3 • Loss of stroke volume variation
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 ThoracSurg1998;65:993–8
Glomerulus from group B (cardiopulmonary bypass at 28°C, for 30 minutes) Smaller glomerulus with narrowedcapillaries suggesting diversion of flow through alternative channels PATHI ET AL RENAL MICROCIRCULATION AND CARDIOPULMONARY BYPASS Ann ThoracSurg1998;65:993–8