**3. Management during cardipulmonary bypass**

Cardiac surgical patients are often dehydrated and hypoglycemic on admission for the operation. Rehydrating the patient and administering sufficient glucose increase the heart's ability to tolerate ischemic arrest. Initiation of bypass results in hypotension, requiring vasoactive drugs (e.g. phenylephrine) to maintain coronary perfusion pressure (CPP). Also ventricular distention should be avoided in order to maintain CPP and avoid the reduction in subendocardial oxygen delivery. After initiation of bypass TEE helps for the intravascular volume monitoring. The heart rate should be maintained <80 bpm in patients with ischemic heart disease during the pre-bypass period. For this purpose β-receptor antagonists can be used to provide a reduction in myocardial metabolism and maximize coronary blood flow (London et al,2008).

The sternotomy is the most distressing period, particularly in reoperations, in which there is a higher risk of right ventricular perforation, damage to existing vein grafts and ventricular fibrillation caused by electrocoutery energy transmission through sternal wires; requiring at least 2 units of RBC readily available in the operating room (London et al, 2008)

During dissection of left internal mammarian artery, the operating table should be elevated and rotated to left, while tidal volumes are to be reduced to facilitate surgeon's exposure.

Anticoagulation is provided by administering 300-400 IU/kg heparin and its adequacy is measured by using activated clotting time (ACT) which is desired to be 450-500 seconds. Higher doses of heparin may be required in case of resistance, however resistance can be treated with 1 unit of FFP or recombinant AT III (Kanbak M, 1999;London et al,2008). If anesthesiologist is the one to administer heparin, then the central venous line is the site of injection, whilst many surgeons prefer to give heparin themselves directly into the RA. Before or after anticoagulation, antifibrinolytic therapy may be initiated for bleeding prophylaxis. Aprotinin, being once the most popular agent, has been withdrawn from the market because of the safety concerns including mortality rate, anaphylaxis and renal dysfunction. Tranexamic acid and aminocaproic acid are the major agents that can be used instead of aprotinin (Henry et al,2007;Umscheid et al,2007)(see also bleeding and transfusion).

After heparinization, aortic cannulation is established often using the ascending aorta, following the examination of the cannulation site to be free of disease (London et al,2008;Morgan et al,2002) . In order to minimize the risk of dissection during cannulation systolic blood pressure should be lowered to a lowest safe level of 90-100 mmHg (London et al,2008).

Myocardial preservation involving anterograde or retrograde cardioplegia or both, arrest with high-potassium cardioplegia and hypothermia (systemic, topical and by cardioplegia) is provided by surgeon and perfusionist (London et al,2008). During cardiopulmonary bypass, pump flows, temperature and glucose control, blood gas analysis and management, ventilation strategies will be discussed later in this chapter.

After revascularization, with adequate rewarming (which will be discussed later in this chapter), stable rhythm-preferably sinus-good response to pacing, acceptable levels of pH, calcium, potassium and hematocrit, adequate ventilation with 100% oxygen; CPB is considered to be terminated (Morgan et al,2002). In case of a potential need, inotropes or other vasoactive drugs should be readily available. Heparin is reversed by protamin at 1:1 ratio emprically avoiding rapid injection. The TEE is removed and stomach is aspirated with an orogastric tube. The chest tubes and mediastinal drainages are secured as chest is closed and get ready for transport (London et al,2008).

#### **3.1 Oxygen delivery during CPB**

Delivery of oxygen depends on two variables that determine tissue oxygenation; hematocrit values and pump flow rates; that the calculation is: DO2= pump flow x ((hemoglobin concentration x hemoglobin saturation x 1.36) + (0.003 x arterial oxygen tension)). In the clinical setting, increasing pump flows, increasing hematocrit concentrations (transfusion of PRBCs or use of ultrafiltration for hemoconcentration), or increasing hemoglobin saturation and the amount of dissolved oxygen (increasing the inspired oxygen concentration [FIO2]) can improve delivery of oxygen (Lango&Mrozinski,2010).

Delivery of oxygen during CPB is typically less than that measured in the awake and anesthetized subjects. This is primarily caused by the decrease in the arterial oxygen content that occurs from hemodilution at the onset of bypass. The reduction in the DO2 is compansated by increasing the oxygen extraction ratio which narrows the safety margin between oxygen supply and demand. At first this compansation maintains oxygen consumption (VO2) stable (flow independent oxygen consumption), when the maximum extraction ratio is reached VO2 and tissue oxygenation begin to decrease and lactic acidosis develops (flow dependent oxygen consumption). The critical DO2 has not been defined, although there are many trials investigating this value; however it is shown that the organs undergoing bypass have hierarchy, that with a low pump flow the DO2 of the brain is maintained at the expense of other organ systems; kidneys, pancreas, muscle beds. In order to preserve organ functions there should be a critical value to be targeted for DO2 rather than targeting pump flow rates or a specific hematoctrit value (Lango&Mrozinski, 2010; Ranucci, 2009).

#### **3.1.1 Hemodilution**

Hemodilution is used during the CPB to offset the effect of hypothermia on blood viscosity and reduce the need for blood transfusion. However with the decreasing hematocrit level, the oxygen carrying capacity decreases and brain compansates for it by increasing CBF and tissue oxygen extraction; which leads to increased embolic load. Although an optimum level for hematocrit during CPB has not been clearly defined, there is data supporting the reservation of transfusion of blood products for the hemoglobin levels of <6 g/dl during CPB and <7 g/dl after surgery (Ferraris et al,2007). When there is a risk for end-organ ischemia these critical values can be increased by 1-7 gr/dl during CPB. Also it is important to know that the critical values can be altered by the clinical situation of the patient (Grogan et al,2008).

is provided by surgeon and perfusionist (London et al,2008). During cardiopulmonary bypass, pump flows, temperature and glucose control, blood gas analysis and management,

After revascularization, with adequate rewarming (which will be discussed later in this chapter), stable rhythm-preferably sinus-good response to pacing, acceptable levels of pH, calcium, potassium and hematocrit, adequate ventilation with 100% oxygen; CPB is considered to be terminated (Morgan et al,2002). In case of a potential need, inotropes or other vasoactive drugs should be readily available. Heparin is reversed by protamin at 1:1 ratio emprically avoiding rapid injection. The TEE is removed and stomach is aspirated with an orogastric tube. The chest tubes and mediastinal drainages are secured as chest is closed

Delivery of oxygen depends on two variables that determine tissue oxygenation; hematocrit values and pump flow rates; that the calculation is: DO2= pump flow x ((hemoglobin concentration x hemoglobin saturation x 1.36) + (0.003 x arterial oxygen tension)). In the clinical setting, increasing pump flows, increasing hematocrit concentrations (transfusion of PRBCs or use of ultrafiltration for hemoconcentration), or increasing hemoglobin saturation and the amount of dissolved oxygen (increasing the inspired oxygen concentration [FIO2])

Delivery of oxygen during CPB is typically less than that measured in the awake and anesthetized subjects. This is primarily caused by the decrease in the arterial oxygen content that occurs from hemodilution at the onset of bypass. The reduction in the DO2 is compansated by increasing the oxygen extraction ratio which narrows the safety margin between oxygen supply and demand. At first this compansation maintains oxygen consumption (VO2) stable (flow independent oxygen consumption), when the maximum extraction ratio is reached VO2 and tissue oxygenation begin to decrease and lactic acidosis develops (flow dependent oxygen consumption). The critical DO2 has not been defined, although there are many trials investigating this value; however it is shown that the organs undergoing bypass have hierarchy, that with a low pump flow the DO2 of the brain is maintained at the expense of other organ systems; kidneys, pancreas, muscle beds. In order to preserve organ functions there should be a critical value to be targeted for DO2 rather than targeting pump flow rates or a specific hematoctrit value (Lango&Mrozinski, 2010;

Hemodilution is used during the CPB to offset the effect of hypothermia on blood viscosity and reduce the need for blood transfusion. However with the decreasing hematocrit level, the oxygen carrying capacity decreases and brain compansates for it by increasing CBF and tissue oxygen extraction; which leads to increased embolic load. Although an optimum level for hematocrit during CPB has not been clearly defined, there is data supporting the reservation of transfusion of blood products for the hemoglobin levels of <6 g/dl during CPB and <7 g/dl after surgery (Ferraris et al,2007). When there is a risk for end-organ ischemia these critical values can be increased by 1-7 gr/dl during CPB. Also it is important to know that the critical values can be altered by the clinical situation of the patient (Grogan

ventilation strategies will be discussed later in this chapter.

can improve delivery of oxygen (Lango&Mrozinski,2010).

and get ready for transport (London et al,2008).

**3.1 Oxygen delivery during CPB** 

Ranucci, 2009).

et al,2008).

**3.1.1 Hemodilution** 

Extreme hemodilution in the elderly should be avoided; a decrease in hematocrit from baseline of 12 percentage points or greater has been shown to be associated with neurocognitive decline (Lombard et al,2010).

Recent guidelines state that heparin-coated bypass circuits (oxygenator alone or the entire circuit) are not unreasonable for blood-conservation (Class IIb, LOE B) (Lango&Mrozinski,2010;Ferraris et al,2007).

Methods to limit the degree of hemodilutional anemia (Lango&Mrozinski,2010)


#### **3.1.2 Intraoperative hemodynamics**

Small and microvascular disease could be a leading cause of dementia in up to two thirds of the patients with dementia. The patients who have dementia at baseline have higher incidence of postoperative cognitive dysfunction, that may be caused by their susceptibility to cerebral hypoperfusion (Lombard et al,2010). Even clinically aymptomatic (no dementia) many patients have infarctions and abnormally perfused areas in brain; these patients are also vulnerable to cerebral hypoperfusion as the surgical population ages with structural changes leading to stiffness in their arteries (Tolwani et al,2008). Cerebrovascular disease may then result in oxygen imbalance during surgery. The use of jugular venous bulb monitoring or near infrared spectroscopy (NIRS) revealed oxygen desaturation 27-43% during rewarming period while cerebral metabolic rate increases (Croughwell et al,1994;HL,2005). DWI detects mostly the watershed stroke, which indicate hypoperfusion brain injury that has been shown to be caused by a decrease from baseline mean arterial pressure (MAP) of >10 mmHg during CPB (Gottesman et al,2006). Maintaining the pre-CPB cerebral perfusion pressures may be an acceptable approach (Burgers et al,2006). NIRS has been used for the detection of oxygen saturation in order to use interventions such as ensuring adequate CPB flow rate, raising the MAP, ensuring normocarbia, deepening anesthesia, raising FiO2 and initiating pulsatile CPB flow; and reported to provide lower rates of major organ injury (death, myocardial infarction, stroke) and shorter ICU length of stay (Murkin et al,2007).

Blood pressure during CPB is often kept >50 mmHg, however many trials and retrospective analysis supporting high pressures as a neuroprotection strategy led the institutions to keep the MAP >70 mmHg, especially in elderly; also according to age many centers manipulate this critical value; >70 mmHg for >70 year-old, >80 mmHg for >80 year-old (Grogan et al,2008). Recent investigations report that the lower limit of cerebral autoregulation may be much higher than 50 mmHg, in awake and normotensive adults the lower limit has been demonstrated to be 73-88 mmHg (Murphy et al,2009 as cited in Larsen et al,1994;Waldermar et al,1989;Olsen et al,1995). Noting that most of the cardiac surgical patients are older, hypertensive and have preexisting cerebrovascular diseases, their autoregulatory curve becomes shifted to the right, which requires higher MAPs (>70 mmHg) to reduce the risk of hypoperfusion (Lango&Mrozinski,2010).

Optimum MAP during CPB is affected by many factors, so decision should depend on the individual case. High-risk patients may benefit from higher pressures on bypass (Lango&Mrozinski,2010).

*Potential advantages of higher MAPs (Lango&Mrozinski,2010)* 


*Potential advantages of lower MAPs* 


Minimally safe pump flow has not been established, however the most commonly used flow rate during bypass is 2.2-2.5 L.min-1.m-2 approximating the cardiac index of a normothermic anesthetized patient with normal hematocrit. During hypothermia pump flow rate as low as 1.2 L.min-1.m-2 have been reported to have good clinical outcomes. Although there are conflicting results, most studies demonstrated that at pump flow rates of 1.0-2.4 L.min-1.m-2, CBF remains constant (Lango&Mrozinski,2010). During severe hemodilutional anemia, increasing pump flows can prevent organ injury, that pump flow may be adapted to hematocrit levels (Ranucci et al,2005). As mentioned before, targeting a critical value for DO2 is more important than targeting pump flows or a specific hematocrit for preserving organ function (Lango&Mrozinski,2010;Ranucci,2005).

#### **3.2 Temperature control**

Hypothermia has been used for decades for cerebral protection. The beneficial effects of hypothermia mainly depend on the two physiologic principles, functional and structural cerebral metabolic need for oxygen that are both reduced by temperature; total cerebral metabolic rate of oxygen (CMRo2) decreases 6-7 % per degree Centigrade reduction; while anesthetic drugs alter only functional CMRo2 (Grigore et al,2009). Thiopental in particular, reduces cerebral metabolic rate required by brain function and synaptic activity, which are achieved during the isoelectric electroencephalographic state. Additional reduction is provided by concomitantly administered hypothermia while preserving CBF-CMRo2 coupling, may also further reduce CBF. Moderate hypothermia without major suppression of neuronal function has been reported to provide better neuroprotection compared with isoelectric doses of barbiturates (Klementavicius et al,1996). Similar effect preserving coupling can be achieved by minimal alveolar concentration (MAC) or sub-MAC doses of volatile anesthetics especially isoflurane. Supramaximal doses uncouple CBF and CMRo2. During profound hypothermia (18-20 C) CBF is disproportionately maintained and is determined more by arterial blood pressure and systemic vascular resistance than by pump flow rates (Grigore et al,2009). Moderate (28 C) and mild hypothermia (32-34 C) was shown to have no difference in terms of cognitive dysfunction, however hyperthermia (especially if the gradient between the temperatures of nasopharyngeal and CPB perfusate is >2C) in the perioperative and postoperative period is clearly associated with neurocognitive decline

Optimum MAP during CPB is affected by many factors, so decision should depend on the individual case. High-risk patients may benefit from higher pressures on bypass

Enhanced tissue perfusion in high risk patients (hypertensive, diabetic, elderly)

Enhanced myocardial protection (reduced collateral coronary blood flow)

Minimally safe pump flow has not been established, however the most commonly used flow rate during bypass is 2.2-2.5 L.min-1.m-2 approximating the cardiac index of a normothermic anesthetized patient with normal hematocrit. During hypothermia pump flow rate as low as 1.2 L.min-1.m-2 have been reported to have good clinical outcomes. Although there are conflicting results, most studies demonstrated that at pump flow rates of 1.0-2.4 L.min-1.m-2, CBF remains constant (Lango&Mrozinski,2010). During severe hemodilutional anemia, increasing pump flows can prevent organ injury, that pump flow may be adapted to hematocrit levels (Ranucci et al,2005). As mentioned before, targeting a critical value for DO2 is more important than targeting pump flows or a specific hematocrit for preserving

Hypothermia has been used for decades for cerebral protection. The beneficial effects of hypothermia mainly depend on the two physiologic principles, functional and structural cerebral metabolic need for oxygen that are both reduced by temperature; total cerebral metabolic rate of oxygen (CMRo2) decreases 6-7 % per degree Centigrade reduction; while anesthetic drugs alter only functional CMRo2 (Grigore et al,2009). Thiopental in particular, reduces cerebral metabolic rate required by brain function and synaptic activity, which are achieved during the isoelectric electroencephalographic state. Additional reduction is provided by concomitantly administered hypothermia while preserving CBF-CMRo2 coupling, may also further reduce CBF. Moderate hypothermia without major suppression of neuronal function has been reported to provide better neuroprotection compared with isoelectric doses of barbiturates (Klementavicius et al,1996). Similar effect preserving coupling can be achieved by minimal alveolar concentration (MAC) or sub-MAC doses of volatile anesthetics especially isoflurane. Supramaximal doses uncouple CBF and CMRo2. During profound hypothermia (18-20 C) CBF is disproportionately maintained and is determined more by arterial blood pressure and systemic vascular resistance than by pump flow rates (Grigore et al,2009). Moderate (28 C) and mild hypothermia (32-34 C) was shown to have no difference in terms of cognitive dysfunction, however hyperthermia (especially if the gradient between the temperatures of nasopharyngeal and CPB perfusate is >2C) in the perioperative and postoperative period is clearly associated with neurocognitive decline

(Lango&Mrozinski,2010).

Allows for higher pump flow rates

Reduction of blood in the surgical field

*Potential advantages of lower MAPs*  Less trauma to blood elements

Less cardiotomy suction

**3.2 Temperature control** 

*Potential advantages of higher MAPs (Lango&Mrozinski,2010)* 

Improved collateral flow to tissues at risk of ischemia

Allows usage of smaller venous and arterial cannulae

Reduced embolic load to the CNS (reduced pump flow)

organ function (Lango&Mrozinski,2010;Ranucci,2005).

(Klementavicius et al,1996). Any potential benefit for cerebral protection of hypothermia can be offset by inappropriate rewarming. More important than the use of hypothermia is avoidance of hyperthermia (Grigore et al,2009). During the rewarming period the returning warmed blood from aortic cannula is in close proximity to cerebral circulation. Also cerebral temperature may be underestimated from the usual monitoring sites (e.g.nasopharynx, esophagus) (Grogan et al,2008). Jugular bulb (JB) is the most reliable site to detect the accurate cerebral temperature, because it receives 99% of the CBF; however it takes time and money with risks associated with placing the device. Nasopharyngeal site and arterial inflow (arterial outlet of membrane oxygenator) temperatures are the closest ones to JB with a gradient of 1-2 C (Grigore et al,2009). Mild hypothermia (32-34 C), slow-rewarming during CPB (maintaining inflow temperature and nasopharyngeal temperature at or below 37 C as the maximum allowable) and avoidance of hyperthermia are the current recommendations (Grigore et al,2009;Grogan et al,2008).

*The effects of hypothermia* 


#### *The effects of hyperthermia*


#### **3.3 Glucose control**

In diabetic patients hyperglycemia may have caused an impaired endothelial function and may attennuate preconditioning. Serum potassium abnormalities should be corrected by glucose and acid-base management. Insulin continuous infusions are recommended for poor glycemic controls, however the possible development of insulin resistance during hypothermic CPB should be considered. Oral hypoglycemic agents; metformin may cause lactic acidosis in patients with low cardiac output state perioperatively, it is to be held several half-lives before the operation and glyburide has been shown to block preconditioning (London et al,2008).

In patients who stays more than 5 days in ICU, aggressive glycemic control was clearly proven to reduce mortality (Van den Berghe et al,2001). Similarly, in a retrospective analysis of cardiac surgical patients a predetermined glucose level (<150 mg/dl) was targeted with a continuous insulin infusion for 3 days postoperatively, had reduced risks of death and deep sternal wound infections (Furnary et al, 2004). There are conflicting results about the association between hyperglycemia and adverse neurological outcome, and yet whether the glycemic control improves neurological outcome is not clear. In diabetic patients hyperglycemia has no influence on cognitive functions and in nondiabetic patients >200 mg/dl glucose level during CPB has been shown to increase the incidence of cognitive dysfunction (Puskas et al,2007). Persistent hyperglycemia (>200 mg/dl) for the 24 hours after stroke, is an independent indicator for the expansion of cerebral infarction (Baird et al,2003). AHA guidelines state that it is reasonable to initiate insulin therapy when glucose level is >140-185 mg/dl (Class IIa, LOE C) after stroke (Adams et al,2007). The NICE SUGAR trial recommends moderate glycemic control compared to intensive control (Finfer et al,2009).

#### **3.4 Blood gas management**

Arterial blood gas pressures are monitored during the bypass period in order to measure the adequacy of oxygenation and CO2 exchange. Hypothermia results in a rightward shift in CO2 dissociation (increased solubility) leading to alkalemia. There are two measurement and management techniques of arterial blood gases depending on the temperaturedependent solubility of CO2; pH-stat (temperature corrected) and α-stat (not temperature corrected). During CPB mostly the measurement and management are done without correction. In α-stat management blood is taken from the hypothermic patient and measured at 37 C; the results are uncorrected and the patient remains alkalotic during CPB. In pH-stat management, the measured partial pressures are corrected for the patients temperatures from the published nomograms, CO2 is added to gas mixture to correct the respiratory alkalosis and low PaCO2. Although there are controversies about the method to be used, pH-stat has been shown to increase the incidence of cerebral injury via obliterating the pressure autoregulation of cerebral blood flow, while α-stat remains to be used in adults preserving pressure autoregulation (Oakes&Mangano,2009).

#### **4. Most common adverse events after cardiac surgery**

#### **4.1 Postoperative atrial fibrillation**

Postoperative atrial fibrillation (POAF) is the most common atrial arrhythmia after cardiac surgery; its importance has become considerable because of the adverse effects it is associated with; such as congestive heart failure, increased need for intraaortic balloon pump, ventricular arrhythmias, cardiac tamponade, perioperative myocardial infarction, need for permanent pacemaker implantation, infection, increased postoperative bleeding, pneumonia, prolonged mechanical ventilation, increased need for tracheostomy, renal failure, stroke and neurological complications including cognitive dysfunction persisting 6 weeks after surgery , although the role of POAF as a cause of these adverse effects has not been clearly defined (Nair,2010). POAF occurs 30% after isolated CABG, 40% after valve surgery and 50% after combined CABG and valve surgery; mostly between days 2 and 4 (Echahidi et al,2008). The attribution of the mechanisms of atrial fibrillation in general population to POAF is difficult that it is not clear. Multiple factors such as ectopic focal depolarization originating from pulmonary veins and inferior vena cava, redistribution of fluid into vascular compartment causing atrial stretch, inadequate atrial protection during aortic cross-clamping, systemic inflammatory response syndrome thus elevated inflammatory mediators in the cardiac chambers and oxidative stress, excessive sympathetic

sternal wound infections (Furnary et al, 2004). There are conflicting results about the association between hyperglycemia and adverse neurological outcome, and yet whether the glycemic control improves neurological outcome is not clear. In diabetic patients hyperglycemia has no influence on cognitive functions and in nondiabetic patients >200 mg/dl glucose level during CPB has been shown to increase the incidence of cognitive dysfunction (Puskas et al,2007). Persistent hyperglycemia (>200 mg/dl) for the 24 hours after stroke, is an independent indicator for the expansion of cerebral infarction (Baird et al,2003). AHA guidelines state that it is reasonable to initiate insulin therapy when glucose level is >140-185 mg/dl (Class IIa, LOE C) after stroke (Adams et al,2007). The NICE SUGAR trial recommends moderate glycemic control compared to intensive control (Finfer

Arterial blood gas pressures are monitored during the bypass period in order to measure the adequacy of oxygenation and CO2 exchange. Hypothermia results in a rightward shift in CO2 dissociation (increased solubility) leading to alkalemia. There are two measurement and management techniques of arterial blood gases depending on the temperaturedependent solubility of CO2; pH-stat (temperature corrected) and α-stat (not temperature corrected). During CPB mostly the measurement and management are done without correction. In α-stat management blood is taken from the hypothermic patient and measured at 37 C; the results are uncorrected and the patient remains alkalotic during CPB. In pH-stat management, the measured partial pressures are corrected for the patients temperatures from the published nomograms, CO2 is added to gas mixture to correct the respiratory alkalosis and low PaCO2. Although there are controversies about the method to be used, pH-stat has been shown to increase the incidence of cerebral injury via obliterating the pressure autoregulation of cerebral blood flow, while α-stat remains to be used in adults

Postoperative atrial fibrillation (POAF) is the most common atrial arrhythmia after cardiac surgery; its importance has become considerable because of the adverse effects it is associated with; such as congestive heart failure, increased need for intraaortic balloon pump, ventricular arrhythmias, cardiac tamponade, perioperative myocardial infarction, need for permanent pacemaker implantation, infection, increased postoperative bleeding, pneumonia, prolonged mechanical ventilation, increased need for tracheostomy, renal failure, stroke and neurological complications including cognitive dysfunction persisting 6 weeks after surgery , although the role of POAF as a cause of these adverse effects has not been clearly defined (Nair,2010). POAF occurs 30% after isolated CABG, 40% after valve surgery and 50% after combined CABG and valve surgery; mostly between days 2 and 4 (Echahidi et al,2008). The attribution of the mechanisms of atrial fibrillation in general population to POAF is difficult that it is not clear. Multiple factors such as ectopic focal depolarization originating from pulmonary veins and inferior vena cava, redistribution of fluid into vascular compartment causing atrial stretch, inadequate atrial protection during aortic cross-clamping, systemic inflammatory response syndrome thus elevated inflammatory mediators in the cardiac chambers and oxidative stress, excessive sympathetic

et al,2009).

**3.4 Blood gas management** 

**4.1 Postoperative atrial fibrillation** 

preserving pressure autoregulation (Oakes&Mangano,2009).

**4. Most common adverse events after cardiac surgery** 

and parasympathetic nervous system activity, as well as physical alterations resulting from incisions to atria may cause POAF (Nair,2010; Grogan et al,2008).

Postoperative atrial fibrillation (POAF) as being associated with various adverse events should be assessed preoperatively and measures to prevent this adverse event should be considered before the operation. Most of the anti-arrhythmic agents that is to be used for prevention of POAF have their own side-effects, that prophylactic usage of these agents should be reserved for patients who are at increased risk for developing POAF. Prevention begins with identifying the patients with potential to develop atrial fibrillation after cardiac surgery (Nair,2010).

*Risk factors for POAF;* 


#### **4.1.1 Prevention of postoperative atrial fibrillation**

#### **Pharmacological methods**

**Β-Blockers:** The withdrawal of β-blockers is a well known cause for POAF. American Heart Association (AHA), American College of Cardiology (ACC) and European Society of Cardiology recommends usage of β-blockers for prevention of POAF (Class I, LOE A) and give a Class IIb, LOE B indication for sotalol (Fauster et al,2006). In a meta-analysis investigating the effect of sotalol vs the other β-blockers revealed that it is superior to the others in preventing POAF, but although not statistically significant sotalol has major bradycardia and hypotensive effects with a significant incidence of torsade-de-pointes (Mitchell et al,2007).

**Amiodarone:** Amiodarone can be used oral or intravenous both before and after the surgery for the prophylaxis of POAF. Amiodarone has been shown to be associated with bradycardia and hypotension (Nair,2010). ACC/AHA/ESC give a Class IIa LOE A indication for amiodarone (Fauster et al,2006). American College of Chest Physicians (ACCP) suggests that amiodarone should be an alternative for patients who have contraindication for β-blockers and Canadian Cardiovascular Society also gives a Class IIa recommendation for amiodarone for the patients who have not been on β-blockers for the prevention of POAF (Bradley et al,2005;Mitchell et al,2005).

**Calcium-Channel Blockers:** Calcium-channel blockers were shown to reduce the incidence of myocardial infarction, ischemia and also tend to reduce mortality. However, these agents exert negative inotropic and negative chronotropic effects which may cause an increase in the incidence of atrioventricular block and low-output syndrome (Nair,2010 ).

**Magnesium:** Magnesium deficiency occurs and may persist for at least 4 days after cardiac surgery. Although ACC/AHA/ESC do not recommend the usage of magnesium as prophylaxis for POAF and ACCP is against its usage, CCS gives Class IIa indication for magnesium usage for patients who are not on beta-blocker therapy (Fauster et al,2006; Nair et al,2010). If magnesium therapy is to be used, it should not be limited to the early postoperative period, that the magnesium deficiency may persist for at least 4 days after cardiac surgery (Nair et al,2010).

**Other Pharmacological Methods:** Digoxin (limited effect) (Mitchell et al,2005), statins (shown to have beneficial effects) (Liakopoulos et al,2009), procainamid (limited usage because of the well-known side effects of Class I antiarrhythmic agents on structural heart diseases) (Nair,2010) and methylprednisolon (beneficial with anti-inflammatory activity but limited usage because of renal adverse side-effects) (Prasongsukarn et al,2005) has been investigated for the prophylaxis of POAF. In patients who have high-risk for the development of AF it is important to continue beta-blockers including the operation day and restart at the earliest postoperative period and as a prophylactic measure to initiate intravenous amiodarone therapy.

#### **Other methods**

Since pericardial effusion has been shown to be an important cause for POAF, posterior pericardiotomy allowing drainage to left pleural space has been investigated and shown to reduce the incidence of supraventricular arrhythmias (Nair,2010). Prophylactic atrial pacing has been shown to reduce the development of POAF. Bi-atrial pacing revealed more significant reduction in POAF vs left or right atrial pacing or no pacing (Fan et al, 2000). It has also been shown to be as effective as the pharmacological measures (Crystal et al,2004;Burgers et al,2006).

### **4.1.2 Treatment of postoperative atrial fibrillation**

POAF is a self-terminating but recurrent tachyarrhythmia that usually subsides in 6-8 weeks after cardiac surgery. It should be kept in mind that the adrenergic response in the postoperative period will reduce the effectiveness of any therapy that does not include betablokers (Nair,2010). POAF treatment should prevent thromboembolism, control ventricular rate, improve hemodynamics, convert and maintain the sinus rhythm and in-long-term prevent tachycardia-associated cardiomyopathy. The treatment strategy that targets only the rate control may not prevent the adverse effects that are caused by atrial fibrillation. Rhythm control has been shown to be no superior than rate control, however, if the symptoms are

**Amiodarone:** Amiodarone can be used oral or intravenous both before and after the surgery for the prophylaxis of POAF. Amiodarone has been shown to be associated with bradycardia and hypotension (Nair,2010). ACC/AHA/ESC give a Class IIa LOE A indication for amiodarone (Fauster et al,2006). American College of Chest Physicians (ACCP) suggests that amiodarone should be an alternative for patients who have contraindication for β-blockers and Canadian Cardiovascular Society also gives a Class IIa recommendation for amiodarone for the patients who have not been on β-blockers for the

**Calcium-Channel Blockers:** Calcium-channel blockers were shown to reduce the incidence of myocardial infarction, ischemia and also tend to reduce mortality. However, these agents exert negative inotropic and negative chronotropic effects which may cause an increase in

**Magnesium:** Magnesium deficiency occurs and may persist for at least 4 days after cardiac surgery. Although ACC/AHA/ESC do not recommend the usage of magnesium as prophylaxis for POAF and ACCP is against its usage, CCS gives Class IIa indication for magnesium usage for patients who are not on beta-blocker therapy (Fauster et al,2006; Nair et al,2010). If magnesium therapy is to be used, it should not be limited to the early postoperative period, that the magnesium deficiency may persist for at least 4 days after

**Other Pharmacological Methods:** Digoxin (limited effect) (Mitchell et al,2005), statins (shown to have beneficial effects) (Liakopoulos et al,2009), procainamid (limited usage because of the well-known side effects of Class I antiarrhythmic agents on structural heart diseases) (Nair,2010) and methylprednisolon (beneficial with anti-inflammatory activity but limited usage because of renal adverse side-effects) (Prasongsukarn et al,2005) has been investigated for the prophylaxis of POAF. In patients who have high-risk for the development of AF it is important to continue beta-blockers including the operation day and restart at the earliest postoperative period and as a prophylactic measure to initiate

Since pericardial effusion has been shown to be an important cause for POAF, posterior pericardiotomy allowing drainage to left pleural space has been investigated and shown to reduce the incidence of supraventricular arrhythmias (Nair,2010). Prophylactic atrial pacing has been shown to reduce the development of POAF. Bi-atrial pacing revealed more significant reduction in POAF vs left or right atrial pacing or no pacing (Fan et al, 2000). It has also been shown to be as effective as the pharmacological measures (Crystal et

POAF is a self-terminating but recurrent tachyarrhythmia that usually subsides in 6-8 weeks after cardiac surgery. It should be kept in mind that the adrenergic response in the postoperative period will reduce the effectiveness of any therapy that does not include betablokers (Nair,2010). POAF treatment should prevent thromboembolism, control ventricular rate, improve hemodynamics, convert and maintain the sinus rhythm and in-long-term prevent tachycardia-associated cardiomyopathy. The treatment strategy that targets only the rate control may not prevent the adverse effects that are caused by atrial fibrillation. Rhythm control has been shown to be no superior than rate control, however, if the symptoms are

the incidence of atrioventricular block and low-output syndrome (Nair,2010 ).

prevention of POAF (Bradley et al,2005;Mitchell et al,2005).

cardiac surgery (Nair et al,2010).

intravenous amiodarone therapy.

al,2004;Burgers et al,2006).

**4.1.2 Treatment of postoperative atrial fibrillation** 

**Other methods** 

not over with rate control only, then rhythm control should also be managed. Rhythm control is recommended for patients who are still symptomatic despite adequate rate control and who cannot achieve an adequate rate control despite therapy. Since it is self-limited, there is no need for long-term therapies for the patients who have normal left ventricular function and restored sinus rhythm. Amiodarone at a maintenance dose for 1 month, up to 3 months maximum, can be used for that kind of patients. Patients with impaired left ventricle function may require longer therapy. ACC/AHA/ECS recommend anticoagulation in addition to rate control (Nair,2010; Fauster et al,2006).

**Rate Control:** The goal in the control of heart rate is 80-90 beats/min after cardiac surgery, however it should be kept in mind that rate should be titrated in order to achieve a stable hemodynamic profile and myocardial oxygen balance. Beta-blockers and amiodarone are the first-line agents to be used for the treatment of POAF (Class I) (Nair,2010;Mitchell et al,2005). Calcium-channel blockers are the other effective agents to be used; diltiazem has been shown to be better tolerated than verapamil. Although digoxin is recommended for the ventricular rate control in patients with AF and congestive heart failure, without preexitation syndromes, has limited efficacy in the postcardiac surgery setting most probably because of the increased sympathetic response after surgery (Nair,2010).

**Rhythm Control:** Although it is self-limited, frequent recurrence is a rule for POAF. After pharmacotherapy in normal setting and also in the settings of recurrence and refractoriness, pharmacological and/or electrical cardioversion to sinus rhythm is also recommended. Amiodarone is the anti-arrhythmic agent to be used for pharmacological cardioversion, propafenon has been shown to be as effective as amiodarone; procainamid, dronedarone are the agents investigated for efficacy and safety, however they have side-effects and limited efficacy compared to that of amiodarone (Nair,2010).

**Electrical Cardioversion:** Postoperative atrial fibrillation may cause hemodynamic deterioration, myocardial ischemia, worsening left ventricle function, rapid ventricular response, which requires electrical cardioversion. The adequate waveform and energy level should be chosen; 120-200 j biphasic and 360 j monophasic is the Class IIa, LOE A recommendation (Neumar et al,2010). When it comes to increasing the dose stepwise, it is important to differantiate the 'failure to cardiovert' and 'early re-initiation of AF'. If even a single beat of sinus rhythm does not occur after cardioversion, it is failure to cardiovert, then increasing the delivered energy level, greater pressure on paddles, internal cardioversion and repeating cardioversion after anti-arrhythmic therapy can be tried. However, if it is early re-initiation of AF, additional measures may also end up in the same situation and may be harmful; that initiation of antiarrhythmic therapy (intravenous amiodarone (high ventricle rates) or diltiazem) and correction of the possible contributing factors (e.g. pain, electrolyte imbalance) before the next electrical cardioversion attempt (24-36 hours later) is recommended. If the unstability continues, DC cardioversion should be given after a bolus dose of amiodarone. For the patients who are stable with a low ventricular rate, observation is recommended until 24-48 hours, if AF still continues DC cardioversion may be attempted (Nair,2010). Combining the pharmacological therapy (amiodarone for at least 7 days, if recurrent AF at least 1 month) with electrical cardioversion prevents the recurrence of atrial fibrillation.

As mentioned earlier, anticoagulation is recommended for patients who receive pharmacological and/or electrical tharpies, because in both cardioversion strategies there is 1-7% risk of thromboembolism. Although the applicability of anticoagulation strategy after cardioversion in non-surgical patients (3-4 weeks of anticoagulant therapy before cardioversion in AF more than 48 hours) for cardiac surgical patients is not clear, it is acceptable to use echocardiography especially for left atrial appendage mural thrombus, immediately placing patient on heparin and continue with oral anticoagulants for 3-4 weeks after cardioversion (Echahidi,2008). POAF is well known to increase the incidence of thromboembolism and stroke, but it is also well known that anticoagulation may result in bleeding and cardiac tamponade. Risk-benefit should be considered before anticoagulant therapy is initiated, especially for patients with advanced age, uncontrolled hypertension and history of bleeding.
