Acute Kidney Injury after Cardiac Surgery: Incidence, Risk Factors and Prevention

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1 Acute Kidney Injury after Cardiac Surgery: Incidence, Risk Factors and Prevention Hong Liu, MD Professor of Clinical Anesthesiology Department of Anesthesiology and Pain Medicine University of California Davis Health System Sacramento, California

2 Disclosure No financial conflict of interests with any products mentioned in the presentation.

3 Background There are approximately 7 million invasive cardiovascular procedures are performed worldwide each year. The major complication rates for valve and coronary artery bypass graft (CABG) surgeries are as high as 48% in the reports. There are 38% CABG patients have some degrees of impaired kidney function Ji et al. Circulation Apr 16; 127(15): Critical Care Published online January 6, 2015

4 Background Patients with impaired kidney function have higher morbidity and mortality rate. AKI is associated with up to 60% mortality rates of all cardiac surgery patients and a 25-fold increase in mortality following cardiac valve surgery. Even mild AKI has associated with increased mortality in critically ill patients. To treat these complications, its estimated costs exceed $20 billion annually.

5 Background Acute kidney injury was associated with increased odds of: Cardiac arrest (OR, 25.3; 95%CI, ; P <.001), Reintubation (OR, 11.3; 95%CI, ; P <.001), Ventilatory failure (OR, 12.4; 95%CI, ; P <.001), Bleeding or transfusion events (OR, 11.3; 95%CI, ; P <.001), and Shock (OR, 11.2; 95%CI, ; P <.001). JAMA Surgery Published online December 3, 2014

6 Etiologies Ischemia and reperfusion injury: the renal medulla has high oxygen consumption but with limited oxygen reserve, is particularly vulnerable Low perfusion pressure: excessive renovascular constriction and obstruction, embolism, excessive anemia, and hypoxemia all predispose to renal ischemia Toxins: free hemoglobin, aminoglycosides and contrast media Inflammation, oxidative stress and immunologic modulation.

7 Ma et al. Acta Anaesthesiologica Taiwanica (2014),

8 Blood Pressure and AKI

9 Pulse Pressure and AKI From an observational database of 5,436 patients undergoing coronary artery bypass graft (CABG) surgery enrolled at 70 centers in 60 countries, the authors demonstrated that a 20 mm Hg increment in pulse pressure (PP) increased the odds of developing renal dysfunction by 50%. An increase in preoperative PP is associated with lower long-term survival after CABG surgery. Circulation. 2007; 115(6): Anesth Analg February 1; 110(2):

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11 Journal of Cardiothoracic and Vascular Anesthesia, Vol28,No3(June),2014:pp

12 The Effect of Hypotension during cardiopulmonary bypass on AKI

13 Increasing mean arterial pressure during cardiac surgery does not reduce the rate of postoperative acute kidney injury. Azau A, Markowicz P, Corbeau J, et al. A single-center randomized controlled study of 300 patients with known risk factors for AKI undergoing elective cardiac surgery with normothermic CBP. In the control group, MAP during CPB was targeted to 50-60mmHg, whereas in the intervention group, the target was 75 85mmHg. The average MAP achieved in the control and intervention groups was 60 and 79 mmhg, respectively. There was no difference in AKI, hospital LOS, or mortality between the 2 groups. Perfusion 2014; 29:

14 Cardiopulmonary bypass and AKI

15 When off-pump coronary artery bypass grafting (OPCAB) was introduced, it was postulated that the avoidance of CPB and its inflammatory response might decrease the incidence and severity of AKI Levy JH, Tanaka KA. Inflammatory response to cardiopulmonary bypass. Ann Thorac Surg 2003; 75:S715 S720. However, A systematic review and meta-analysis of 22 randomized controlled trials (4,819 patients) suggested that OPCAB may be associated with a lower incidence of CSA-AKI, however, without a decrease in the requirement for renal replacement therapy (RRT). Seabra VF, Alobaidi S, Balk EM, et al. Off-pump coronary artery bypass surgery and acute kidney injury: a meta-analysis of randomized controlled trials. Clin J Am Soc Nephrol 2010; 5:

16 The CABG Off or On Pump Revascularization Study (CORONARY) investigators 4752 patients in 79 centers in 19 countries to off-pump or on-pump CABG. There was no difference in the primary composite outcome measure of the 30- day mortality, myocardial infarction, stroke, or renal failure requiring dialysis. Lamy A, Devereaux PJ, Prabhakaran D, et al. Off-pump or on-pump coronaryartery bypass grafting at 30 days. N Engl J Med 2012; 366: Although OPCABG induced less AKI, this was not associated with better clinically meaningful or important outcomes at one year. Garg AX, Devereaux PJ, Yusuf S, et al. Kidney function after off-pump or onpump coronary artery bypass graft surgery: a randomized clinical trial. J Am Med Assoc 2014; 311:

17 Transfusion and risk of acute kidney injury in cardiac surgery Can J Anesth 2014

18 In one study of 1,210 adults undergoing cardiac surgery, the authors concluded that the risk of AKI was highest in patients receiving more than two units RBCs. Khan UA, Coca SG, Hong K, et al. Blood transfusions are associated with urinary biomarkers of kidney injury in cardiac surgery. J Thorac Cardiovasc Surg 2014; 148:

19 Preoperative anemia with intraoperative RBC transfusion was associated with AKI Erythrocytes undergo irreversible morphological and biochemical changes during storage. As a result, after transfusion, they can promote a pro-inflammatory state, impair tissue oxygen delivery, and exacerbate tissue oxidative stress. This in turn can cause AKI in susceptible patients undergoing cardiac surgery with CPB, such as those with pre-existing kidney dysfunction or anemia. British Journal of Anaesthesia 109 (S1): i29 i38 (2012)

20 How to limit transfusion associated AKI 1. decrease other fluid (hemodilution) 2. retrograde autologous priming of the cardiopulmonary circuit 3. salvage of shed blood 4. tolerance of moderate hemodilution 5. early identification and treatment with erythropoietin-stimulating agents and iron therapy 6. treat anemic patients with prophylactic transfusions 1 2 days before surgery British Journal of Anaesthesia 109 (S1): i29 i38 (2012)

21 Pharmacological Agents in Cardiac Surgery a 2 Agonists Dopamine and its analogues. Diuretics. Calcium channel blockers. Angiotensin-converting enzyme (ACE) inhibitors. Hydration fluids. N-acetyl cysteine. Atrial natriuretic peptide. Erythropoietin (EPO). Sodium bicarbonate. Aspirin. Interventions for protecting renal function in the perioperative period (Review) Copyright 2013 The Cochrane Collaboration

22 Dexmedetomidine

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25 Mechanisms of Action Attenuation of sympathetic response by activation of α 2 c receptors in the wall of vascular smooth muscle maintaining renal blood flow and GFR Dexmedetomidine can also exert direct vascular effects in the kidneys by decreasing the sympathetically mediated presynaptic release of norepinephrine in the kidneys, which could promote renal arterial vasodilatation Induction of diuresis by suppressing arginine vasopressin It has been reported in animal models that dexmedetomidine persevered calculated creatinine clearance and reduce the severity of AKI by preventing tubule obstruction and decreasing oxygen consumption.

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27 Aspirin

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30 The mechanism responsible for the beneficial effects of aspirin in patients with CKD under going cardiac surgery remain to be investigated but are more likely related to its dual role as an antiplatelet and antiinflammatory agent. In our preclinical animal study, aspirin treatments significantly reduced levels of neutrophil gelatinaseassociated lipocalin (NGAL), a biomarker of kidney injury, in the kidney and plasma in rats with renal ischemia and reperfusion (the results unpublished yet), indicating that NGAL is involved in aspirininduced therapeutic effect. (Ann Surg 2015;261: )

31 ACEi/ARB

32 J Cardiothorac Vasc Anesth. 2013; 27(4):

33 J Cardiothorac Vasc Anesth. 2013; 27(4):

34 RAS inhibitors could improve endothelium-dependent relaxation by decreasing endothelial-derived adhesion molecule production. These also have also been demonstrated to improve gut perfusion and reduceend-organ failure in critically ill patients. Studies also have found that RAS inhibitors can prevent lipopolysaccharide- induced septic shock and block lipopolysaccharide-induced inflammatory response in animal model. The authors suggested that enalapril would be a good therapeutic agent for sepsis. The reduction of septicemia in the RAS inhibitor group was likely to be associated with the reduction of AKI J Cardiothorac Vasc Anesth. 2013; 27(4):

35 Sodium Bicarbonate

36 In a meta-analysis of trials of sodium bicarbonate in cardiac surgery that included five RCTs and one prospective observational cohort study (a total of 1673 patients). There was no difference in the incidence of AKI. Urinary alkalinization is currently not recommended for the prevention of contrast induced nephropathy(cin). Schiffl H. Sodium bicarbonate infusion for prevention of acute kidney injury: no evidence for superior benefit, but risk for harm? Int Urol Nephrol [Epub ahead of print] Turner KR, Fisher EC, Hade EM, et al. The role of perioperative sodium bicarbonate infusion affecting renal function after cardiothoracic surgery. Front Pharmacol 2014; 5. Tian ML, Hu Y, Yuan J, Zha Y. Efficacy and safety of perioperative sodium bicarbonate therapy for cardiac surgery-associated acute kidney injury: a meta-analysis. J Cardiovasc Pharmacol 2015 [Epub ahead of print] contrast-induced nephropathy (CIN)

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39 Erythropoietin

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41 Ultrafiltration

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43 Thank You!