Cardiopulmonary bypass and blood contact with synthetic surface of CPB circuit can promote whole-body systemic inflammatory response that plays a role in multiorgan failure. Continuous exposure of heparinized blood to foreign surfaces in the perfusion circuit and nonendothelial cells in the wound provoke complement anaphylatoxins, adhesion molecules, proinflammatory cytokines, vasoactive substances, coagulation, and fibrinolytic activation. In addition, ischemic–reperfusion injury (due to aortic clamp and declamping), endotoxemia (due to splanchnic hypoperfusion), hypothermia, surgical trauma, blood loss, and transfusion may contribute in activation of inflammatory cascade. Leukocyte activation, especially neutrophil, is responsible to initiate the release of inflammatory mediators that have negative impact in all organs. The severity of this exaggerated response can range from being barely clinically detectable to respiratory failure, coagulopathy, and multiorgan dysfunction. There are suggested strategies to attenuate inflammatory response, though there is not a consensus regarding their clinical outcome and benefits; these include heparin-coated circuit, corticosteroids, hemofiltration, leukocyte depletion, minimized extracorporeal circulation, aprotinin, complement inhibitors, free radical scavengers, and antioxidants (Miller and Levy 1997; Paparella et al. 2002; El Kebir et al. 2005; Raja and Dreyfus 2005; Patel and Ghatak 2008; Warren et al. 2009a, b; Rimmele et al. 2010; Augoustides 2012; Dieleman et al. 2012; Hausenloy et al. 2012).

All blood elements get impression during CPB due to activation of haemostatic–inflammatory system. Pump time duration and the influence of biomaterial substances in surface area of CPB have the most effect on the severity of humoral and cellular activation. In coagulation system, reduction in platelet count and function, consumption of coagulation factors and increased activity in fibrinolytic field occur. Blood contact with artificial surfaces of CPB circuit makes intrinsic coagulation pathway activation. Extrinsic coagulation pathway is activated in pericardial blood, which is usually aspirated and returned to pump circulation. In addition to mechanical trauma to red blood cell, mixture of blood with priming solution brings to a dilutional anemia in the beginning of CPB. There are strategies to decrease this response: heparin coating of CPB circuit, corticosteroids, leukocyte filter, and ultrafiltration (Chung et al. 1996).

Prevalence of acute kidney injury (AKI) after cardiac surgery has been reported between 1 and 30 %, according to definitions used for AKI, as there is no consensus in definition. It is associated with significant short- and long-term mortality. After cardiac surgery, only minimal changes of serum creatinine as small as 0.3 mg/dL predict prognosis in this setting, even it remains in normal range too; so attention to preventable causes, early detection, and treatment are among the valuable issues for prevention of AKI after cardiac surgery (Ronco et al. 2002; Boldt et al. 2003; Lassnigg et al. 2004; Karkouti et al. 2005; Mitter et al. 2010; Moriyama et al. 2010; Park et al. 2010b; Mariscalco et al. 2011; Weir et al. 2011; Ko et al. 2012; Kohagura and Ohya 2012; Sviglerova et al. 2012; Tolpin et al. 2012).

The most important causes of AKI during CPB (which overlap and interact at the cellular level):

CPB per se is responsible for renal injury duo to non-pulsatile flow. Other factors that are related to CPB include duration of CPB time and cross-clamp time, hemolysis, and hemodilution.

During operation modifiable factors that reduce the risk of AKI are prevention of excessive hemodilution, shorter duration of CPB, optimal glucose control, and use of NaHCO₃. In practice kidney function is assessed by measuring serum creatinine, but it has limitations. Rise in serum creatinine indicates the reduction of glomerular filtration rate and occurs slowly in several days after proved injury. So it is an unreliable and insensitive indicator during early stages of kidney injury. Multiple studies have suggested that NGAL (neutrophil gelatinase-associated lipocalin) is a sensitive biomarker that shows tubular cell damage as early as 2 h after the event. It can be used as a reliable marker to diagnosis of acute kidney injury in post-cardiac surgery (Ronco et al. 2002; Boldt et al. 2003; Lassnigg et al. 2004; Karkouti et al. 2005; Mitter et al. 2010; Moriyama et al. 2010; Park et al. 2010a, b; Mariscalco et al. 2011; Weir et al. 2011; Bayrak et al. 2012; Ko et al. 2012; Kohagura and Ohya 2012; Levi et al. 2012; Sviglerova et al. 2012; Tolpin et al. 2012; Vellinga et al. 2012; Yap and Lee 2012).

Pulmonary dysfunction and prolonged ventilation after cardiac surgery are important causes of morbidity. It occurs due to combined effects of anesthesia, surgical trauma, and CPB. Causative factors of pulmonary impairment function during cardiac surgery are:

Lack or reduced blood flow through the lungs during surgery increases the damage of other factors. As the lung perfusion is limited to bronchial arterial system during aortic cross-clamp period. The clinical pattern of this injury has a range from subclinical functional changes to ARDS, due to lung edema, atelectasis, increased alveolar–arterial oxygen gradient, abnormal gas exchange, increased intrapulmonary shunting, and decreased lung compliance. Studies showed that neutrophil accumulation in lung during CPB, its activation, release of chemical mediators, and proteolytic enzymes are in charge of lung injury. In addition to inflammation response, volume overload during CPB plays an important role in accumulation of interstitial fluid in lung too. It was shown that prolonged CPB time, aortic valve surgery, and combined valve/CABG procedures are independent factors of postoperative respiratory failure. There are some therapeutic intervention to prevent or treat pulmonary dysfunction, such as corticosteroid administration, leukocyte depletion, heparin-coated circuit, hemofiltration, maintaining pulmonary ventilation during CPB, maintaining pulmonary perfusion during CPB, pump time reduction, and use of minimized CPB (Carvalho et al. 2008; Filsoufi et al. 2008; Goebel et al. 2008; Suzuki 2010).

Neurologic abnormalities such as stroke (prolonged or permanent deficit) and post- operative cognitive dysfunction are relatively common problems despite improvement in anesthetic and surgical techniques. They are important and disturbing complications after cardiac surgery. The independent predictors of postoperative stroke are:

CPB-related mechanisms include:

The majority of strokes are due to embolic event, and watershed component is seen in few patients; the most atheromatous embolic event happens during manipulation of atherosclerotic aorta (cannulation, cross-clamp, and declamping), and its consequences are crack or rupture of atherosclerotic plaque leading to debris release, cerebral embolization, and ischemic brain injury. Aortic clamping in the presence of exophytic plaque is contraindicated, and elimination of CPB is recommended in this condition. It is suggested that epiaortic ultrasonography be used to identify atheromatous plaque and help to select the suitable site for aortic cannulation in the diseased ascending aorta. It is more sensitive than digital palpation and transesophageal echocardiography and gives information about the entire length of the ascending aortic wall; it can affect the rate of stroke whenever operative strategies are changed. Prevention of microemboli is accomplished by the use of a membrane oxygenator, the prevention of air entering the circuit, and the use of a microfilter that will effectively trap microemboli and prevent from reentering the blood stream and preventing the manipulation of diseased aorta. Prolonged period of hypoperfusion is a predisposing factor of ischemic events especially in old, diabetic, and hypertensive patients who have impaired autoregulatory mechanism in cerebral circulation; maintaining high perfusion pressure is recommended in these patients during CPB. Cerebral oximetry monitor can be used to assess cerebral perfusion during cardiac surgery. Decrease and increase in temperature of brain (during cooling and rewarming period) happens more quickly than other parts of the body because of the well- perfused state. Rapid rewarming at the end of CPB can lead to cerebral hyperthermia and exacerbated neurologic dysfunction. During complex aortic arch surgery, neurologic complication is associated less in antegrade cerebral perfusion (through right axillary artery cannulation) than retrograde cerebral perfusion and deep hypothermic circulatory arrest; in these patients femoral artery cannulation has the risk of retrograde cerebral embolization and worse neurologic outcome. Those who experience stroke during 24 h of CPB had adverse outcome in contrast to late presentation, although the majority of strokes happen after initial normal neurologic recovery of CPB, delayed stroke. Cognitive disorder such as a decrease in baseline performance is more frequent than neurologic deficit by the same mechanisms. Mild hypothermia is recommended for the reduction of postoperative cognitive disorder (Hogue et al. 1999, 2007, 2008a, b; Puskas et al. 2000; Salazar et al. 2001; Ascione et al. 2002; Bucerius et al. 2003; Bergman et al. 2004; Carrascal et al. 2005; Zingone et al. 2006; Biancari et al. 2007; Nathan et al. 2007; Campos and Paniagua 2008; Gottesman et al. 2008; Grogan et al. 2008; Lisle et al. 2008; Tully et al. 2008; Grigore et al. 2009; Slater et al. 2009; Coburn et al. 2010; Lombard and Mathew 2010; Rudolph et al. 2010; Hedberg et al. 2011; El Zayat et al. 2012; Messerotti Benvenuti et al. 2012a, b; Misfeld et al. 2012; Sanders and Grocott 2012; Sun et al. 2012; Bartels et al. 2013; Bruggemans 2013; Reinsfelt et al. 2013).