Predictors and Prognostic Implications of Post-Cardiac Surgery Multiorgan Failure:
Introductary Remarks
Dina H. Rimawi, MS; Ramzy H. Rimawi, MD
Cardiac surgery involves the use of cardiopulmonary bypass (CPB), which distinguishes it from other types of surgery and introduces a distinctive set of potential postoperative complications. Despite advances in the preoperative preparation, CPB, and postoperative management, complications involving the cardiac and other organ functions often occur. At times, multiple organs can progressively become compromised, causing multiorgan dysfunction (MOD). Cardiac surgery is associated with a low incidence of MOD, but when the latter develops, it results in a disproportionate rise of mortality risk.
In the intensive care unit (ICU), MOD is a prominent cause of morbidity and mortality after cardiac surgery [1]. MOD can significantly alter the patients morbidity, mortality, length of stay, mechanical ventilation days, and incidence of stroke, deep sternal wound infection, renal failure, and need for reoperation. As more organs become dysfunctional, the mortality rate rises. For example, the incidence of one organ dysfunction is 73.6%, which corresponds to a 21.1% mortality risk, while the incidence of developing ≥ 4 organs dysfunction is 1%, yet corresponds to a mortality risk of 76.2% [2]. In this chapter, we will discuss the epidemiology, etiology, diagnosis, and management of the major organ dysfunctions associated with cardiac surgery.
Pulmonary
Given the physiologic inter-dependence of the cardiac and pulmonary systems along with the uniform use of mechanical ventilation during and after thoracic surgery, respiratory impediments remain a prominent cause of morbidity, ICU length of stay (LOS), healthcare costs, and mortality after cardiac surgery [3]. Morbidity, LOS, and mortality six months post-cardiac surgery is greater in clinical situations where combined cardiac and respiratory failure occur (51%) as opposed to when respiratory failure alone is encountered (36%). Post-cardiac pulmonic complications can be related to a primary cardiac disorder (cardiogenic pulmonary edema, congestive heart failure), intrinsic pulmonary disorder (atelectasis, pneumonia, pulmonary embolism), or a complication of CPB (post-pump lung syndrome, acute respiratory distress syndrome). Post cardiac procedure complications may occur early (difficulty in liberating from the ventilator) or late (need for mechanical ventilation reinstitution), with the most common causes being; pneumonia (78%), cardiogenic pulmonary edema and adult respiratory distress syndrome (5%) [4]. Risk factors for pulmonary dysfunction that may lead to MOD have been well described, including [5]:
1. Preoperative variables:
a) age ≥ 75 years
b) body mass index ≥ 30 kg/m2
c) mean pulmonary artery pressure ≥ 20 mmHg
d) stroke volume index ≤ 30 mL/m2
e) low serum albumin
f) cerebrovascular disease
g) emergency surgery
h) CPB time ≥ 140 minutes
2. Postoperative variables include:
a) an immediate postoperative hematocrit < 30%
b) mean systemic arterial pressure < 90 mmHg
c) cardiac index < 3.0 L/min/m2
The principle cause of pulmonic complications after cardiac surgery is a low cardiac output (CO) state [6]. A reduction in CO can (1) increase pulmonary capillary pressure and subsequent positive fluid balance, resulting in cardiogenic pulmonary edema and congestive heart failure; (2) fatigue, which results in weakened cough, poor inspiratory efforts and lung mechanics attributing to atelectasis, pulmonary effusions, and/or pneumonia; (3) ≥ 50% reduction in FVC, FEV1, PEFR, and maximum voluntary ventilation (MVV) affecting rib cage expansion. FRC and FEV1 are more affected when internal mammary artery grafts are used rather than saphenous vein grafts [7].
While off-pump and on-pump surgery have similar affects on lung mechanics (FVC, FEV1), alveolar-arterial oxygen gradient, tissue elastance, and inspiratory resistance, patients who undergo on-pump surgery have substantial expansions in expiratory airway resistance [8]. There is less pain and time to return to baseline pulmonary function after ministernotomy or thoracoscopy as compared to median sternotomy, though no difference in mechanical ventilation days is seen [9]. On the contrary, minithoracotomies and thoracoscopy require one-lung ventilation, which may cause atelectasis during the deflated state of the non-ventilated left lung.
Reductions in pulmonic complications may be difficult to achieve, though efforts should be made to liberate patients from the ventilator earlier, improve oxygenation/ventilation, and encourage chest physiotherapy. Atelectasis, which leads to reduced PaO2 and functional lung volume, may be prevented via continuous positive airway pressure (CPAP) during CPB and positive end expiratory pressure (PEEP) immediately after CPB [10]. Recruitment maneuvers before stopping CPB reduces shunting, time to extubation by approximately 3 hours [11]. Noninvasive ventilation with conventional chest physiotherapy plus incentive spirometry after extubation can improve FRC, VC, FEV1 and PAO2 to preoperative levels.
Pleural effusions may be the first sign of impending respiratory failure and subsequent MOD. Effusions may be caused by bleeding, pneumonia, cardiogenic pulmonary edema, ARDS, pleurotomy, atelectasis, pleural lymphatic drainage disorder, leaking of mediastinal fluid, and/or chylothorax [12]. While most effusions resolve within a year, thoracentesis or chest tubes may be required depending on the size of the effusion and potential effects on respiratory performance. Pneumonia after cardiac surgery is a prominent cause of respiratory failure. The incidence may be higher if there is a history of smoking, chronic obstructive pulmonary disorder (COPD), failure to thrive, immunosuppression, atelectasis, aspiration, reintubation, presence of a nasogastric tube, transfusion of ≥ 4 units of blood products, and/or treatment with broad-spectrum antibiotics or H2-receptor blocking agents. Pneumonia after cardiac surgery can increase mortality dramatically because of the propensity for MOD. As each day of mechanical ventilation increases the risk of pneumonia by 1%, efforts should be made to liberate patients from the ventilator as early as possible [13]. Post-cardiac surgery pneumonia can be curtailed via using closed system suction catheters, continuous subglottic suctioning, maintaining semi-recumbence, early ambulation, and maintaining normoglycemia [14].
Cardiogenic pulmonary edema can increase the risk of MOD, therefore improving the underlying cardiac function with inotropic agents, afterload reduction, diuretics, and/or insertion of an intra-aortic balloon pump (IABP) should be considered. On-pump surgery causes a systemic inflammatory response that can lead to increased pulmonary endothelial permeability and subsequent non-cardiogenic pulmonary edema. Although ARDS after CPB only occurs in less than 2% of patients, the mortality rate can be as high as 80%, emphasizing the need for protective lung strategies in intubated patients after cardiac surgery [15].
Cardiac surgery can induce a hypercoagulable state, which can lead to thromboembolic events and subsequent MOD. The reported incidence of pulmonary embolism after cardiac surgery ranges from 0.3% to 9.5%, with an incidence of fatal pulmonary embolism of 0.5% [16]. Deep venous thrombosis prophylaxis should be initiated as soon as possible to reduce the incidence of venous thromboembolic events after cardiac surgery. Aspirin and elastic gradient compression stockings should be used in patients who ambulate within 2 to 3 days after surgery, while low-molecular-weight heparin and sequential compression stockings should be used in bedridden patients [17].
Cardiac
It is not surprising that cardiac dysfunction after cardiac surgery is a major cause of MOD. Postoperative cardiac complications may include bleeding, pericardial tamponade, arrhythmias, right and/or left ventricular failure, coronary vessel restenosis, valvulopathy, and the less frequently cardiac wall rupture and/or perforation. Both tachyarrhythmias and bradyarrhythmias represent a major cause of morbidity, increased LOS, economic burden, MOD, and mortality. Though atrial tachyarrhythmias (atrial fibrillation) is the most common arrhythmia after cardiac surgery, ventricular arrhythmias and conduction disturbances may also transpire [18]. Postoperative atrial fibrillation is typically self-limiting, but can require anticoagulation therapy and rate/rhythm control strategies. Sustained ventricular arrhythmia in the absence of a reversible cause(s) often warrants immediate attention and long-term preventive therapy. Transitory bradyarrhythmias can be managed with temporary pacing wires, though permanent pacing may be needed for significant and persistent atrioventricular block or sinus node dysfunction.
Several risk factors for postoperative cardiac complications that may lead to MOD have been described. An elevated preoperative brain natriuretic peptide plasma concentration is a predictor of postoperative cardiac dysfunction [19]. Increasing age correlates with postoperative cardiac dysfunction, in that the odds ratio for developing postoperative atrial fibrillation is 1.51 per decade [20]. Patients with structural heart disease, including atrial enlargement or elevation in atrial pressures, undergoing cardiac surgery have an increased predisposition to atrial tachyarrhythmias. Cardiomegaly can be attributed to a ventricular arrhythmogenic substrate. Prior arrhythmias (principally atrial fibrillation), cardiac surgery, congenital heart disease, right coronary or atrioventricular nodal artery disease, valvulopathy, obesity, cerebrovascular disease, and COPD represent other notable risk factors for cardiac dysfunction [21].
Intra-operative cardiac complications are a major cause of cardiac dysfunction. The trauma related to cardiac surgery can result in atrial and ventricular arrhythmias, pericarditis, and pericardial effusions. Perioperative hypoxia, hypercarbia, instrumentation, endogenous/exogenous catecholamines, acid-base disturbances, hypokalemia, hypomagnesemia, CBP time, and/or drug effects (i.e. cardiplegia) can cause cardiac ischemia.
Preoperative beta-adrenergic blockade and digoxin can reduce the rate of postoperative supraventricular arrhythmias [21,22]. Inotropic agents can be arrhythmogenic due to increase in sinoatrial node automaticity and decrease in AV nodal conduction time. Preservation of the anterior epicardial fat pad during cardiac surgery had been shown to reduce the risk of postoperative atrial fibrillation [23]. a transplanted heart may be subject to arrhythmogenesis and cardiac dysfunction to due to ischemia during organ preservation, organ rejection, atherosclerosis, denervation, or structural anomalies such as wide surgical suture lines [24].
Isolated premature ventricular complexes (PVC), typically related to metabolic imbalances, are common after cardiac surgery and rarely necessitate acute treatment or long-term antiarrhythmic therapy. Though frequent PVCs (>30 per hour) in a patient with impaired left ventricular and an ejection fraction <40% may lead to worsened ventricular function and subsequent higher risk of MODS or mortality. [25] In patients with hemodynamic compromise related to PVCs, lidocaine can be used for refractory PVCs after metabolic/electrolyte imbalance correction. Sustained ventricular arrhythmias, notably ventricular tachycardia (VT) and ventricular fibrillation (VFib) can occur, and accordingly redispose to MOD, as a result of hypoxia, hemodynamic instability, electrolyte disturbances, hypovolemia, medications (inotropes, antiarrhythmic agents), myocardial ischemia/infarction, infection, graft stenosis, and reperfusion after cessation of CPB. While asymptomatic non-sustained VT (NSVT) often do not merit therapy other than the correction of reversible causes, symptomatic NSVT can be managed with overdrive pacing, lidocaine, procainamide, or amiodarone [26]. Hemodynamically unstable sustained VT should be promptly chemically or electrically cardioverted. Refractory VT occuring in the immediate peri-operative periodor may necessitate initiation of emergent CPB on the short term and insertion of an implantable cardioverter-defibrillator for long term protection.
Neurologic
Though neurologic decline is often transient after cardiac surgery, persistent cognitive decline after an early improvement stage can suggest further neurologic dysfunction and subsequent MODS [27]. Despite advances in cardiac surgery, neurological complications, including ischemic stroke, delirium, and persistent cognitive decline, still commonly occur. Ischemic stroke is perhaps the most severe neurologic complication caused by perioperative cerebral thromboembolism or hypoperfusion injury. The incidence of cerebrovascular accidents after cardiac surgery has progressively declined to rates of 1-5% [28]. For patients with significant atherosclerotic vascular disease, assessment for carotid disease (i.e. carotid duplex screening) should be done prior to cardiac surgery and consideration for simultaneous or staged combined carotid and coronary revascularization should be sought in patients with symptomatic carotid disease.
Perioperative strokes can occur early (pre-extubation) or late (post-extubation) and can arise from different pathophysiological processes. Early or intraoperative cerebrovascular accidents can be due to peripheral and carotid vascular disease, prior cardiac surgery, low intraoperative mean arterial pressure, poor perioperative glycemic control, poor baseline clinical and/or cognitive condition, left ventricular dysfunction, carotid stenosis >70%, on-pump surgery, hypothermic circulatory arrest, preoperative creatinine elevation, atherosclerosis, increased CPB time, older age, and/or coagulopathy. Late or postoperative stroke can arise in patients with left main stenosis, diabetes, female sex, anemia, low body surface area, unstable angina, postoperative arrhythmia, sepsis, valvular surgery (9.7% for multivalve surgery versus 3.8% for CABG), or inotropic support. Post-cardiac surgery delirium is more likely to occur in the patients older than 65 years, postoperative or previous stroke, mechanical ventilation > 24 hours, postoperative renal insufficiency, blood product administration, concomitant CABG and valvular surgery, preoperative benzodiazepine use, female gender, history of depression, low education or baseline cognitive scores, and comorbidities [29].
Aspirin, if initiated within 48 h of revascularization, can reduce the incidence of perioperative stroke by 50% [30]. Preoperative statin therapy reduces the postoperative atrial fibrillation, LOS, stroke, cognitive dysfunction and mortality [31]. Although localized intra-arterial thrombolysis has been used safely in stroke patients after cardiac surgery, systemic thrombolysis should be avoided within 14 days [32]. Though evidence exists for the feasibility of therapeutic hypothermia in patients with stroke after cardiac surgery, its’ efficacy and safety has not been well studied. Efforts to reduce the incidence of delirium after cardiac surgery include neuroleptic prophylaxis (i.e. risperidone), use dexmedetomidine rather than benzodiazepines or propofol, sedation and neuromuscular blockade minimization, and early mobilization [33].
Gastrointestinal
Postoperative gastrointestinal (GI) complications after cardiac surgery, while rare, can result in rapid MOD and subsequent death in 17-50% of patients [34]. Gastrointestinal dysfunction can come in a variety of presentations, including intestinal bleeding or ischemia, pancreatitis, cholecystitis, hepatic failure, and ileus. The overall incidence of GI dysfunction is 0.3%-2%, with a consequential mortality ranging from 10%-60% usually secondary to MOD [35]. Research has allowed us to understand how GI dysfunction seem to all revolve around hypoperfusion.
Risk factors include age > 70 years, perioperative cardiac output failure, hypovolemic hypotension, prolonged CPB time, postoperative blood transfusions, need for emergency surgery or reoperation, triple-vessel disease, New York Heart Association functional class IV, inotropic support, arrhythmia, renal or hepatic failure, previous GI surgery, prolonged mechanical ventilation, peripheral vascular disease, and congestive heart failure. Numerous studies have reported the strong association between CPB time, renal dysfunction, and protracted ventilation with GI dysfunction after CABG, likely related to visceral vasoconstriction and subsequent splanchnic hypoperfusion. Counterpulsation via intra-aortic balloon pumps may result in atheroemboli in the extremities and viscera of patients with severe aortoiliac arteriosclerotic disease.
Hepatic blood flow is reduced by approximately 20% during CPB, more so especially during hypothermic temperatures (28-30 C) [36]. Interestingly, preoperative alcohol intake and elevated hepatic enzymes were not associated with an increased risk of hepatic failure after cardiac surgery, while elevated right atrial pressure, CPB time > 80 minutes, and multiple valve replacements were [37].
Measures to reduce GI dysfunction can occur preoperatively and postoperatively. Preoperatively, clinicians should identify severe abdominal aorta and secondary branch arteriosclerosis. Intraoperatively, avoidance of prolonged CPB, hypovolemic hypotension, and on-pump myocardial revascularization can help mitigate splanchnic perfusion. In patients with severe abdominal aortic disease, judicious use of vasoconstrictors and intra-aortic balloon pump counterpulsation should be considered. If at all possible, postoperative bleeding in high-risk patients should be managed with early re-exploration to avoid prolonged periods of hypotension and blood transfusions. If mechanical ventilation must be used, PEEP should be limited as it can induce angiotensin and catecholamine production, leading to splanchnic vasoconstriction [38]. Early liberation from the ventilator, IABP, vasopressors, and correction of arrhythmias can help reduce the complications related to GI dysfunction after cardiac surgery.
Renal
The incidence of post-cardiac surgery acute kidney injury (AKI) can range from 50% having mild AKI renal injury (creatinine rise <25%), 8-15% having moderate kidney injury, and 5% developing end-stage kidney injury and requiring dialysis [39]. AKI after cardiac surgery can lead to myocardial infarction, bleeding necessitating reoperation, infection, MOD, and mortality. Mortality is rare in patients with renal failure after cardiac surgery unless complicated by multiorgan failure or sepsis [40].
As with GI dysfunction, renal dysfunction after cardiac surgery is principally secondary to hypoperfusion which may occur during or after CPB. In additional, AKI after cardiac surgery can be related to nephrotoxic agents, atheromatous plaques, platelet aggregates, emboli, metabolic factors, neurohormonal activation, and/or oxidate stress. Risk factors include preoperative renal dysfunction, valvular surgery, IABP, need for reoperation, decreased ejection fraction or cardiac output, peripheral vascular disease, congestive heart failure, COPD, prolonged CPB time, severe hypertension or hypotension, advanced age, diabetes, on-pump surgery, preoperative hyperglycemia, sepsis, and anemia with need for blood product transfusion [41].
Renal dysfunction can be diagnosed by abnormal creatinine levels, low urine output, urinalysis including evaluation for casts, and/or novel biomarkers including neurotrophil-gelatinase-associated lipocalin and cystatin C [42]. Renal ultrasound can help assess for obstructive causes or renal artery stenosis. Nephrology evaluation should be considered in persistent, worsening or severe AKI to help assess further diagnostic testing.
Preventative strategies include adequate hydration, maintenance of normotension/ normoglycemia/ normothermia, sodium bicarbonate, and dopaminergic or diuretic drugs depending on the etiology [40]. Treatment involves treating the underlying cause, including cessation of nephrotoxins if possible, correction of metabolic disorders, normalization of blood pressure, and renal replacement therapy.
Hematologic
Hematologic dysfunction after cardiac surgery can be difficult to manage given the need for anticoagulation in the setting of normal homeostasis restoration. After CPB, hematologic dysfunction can include coagulation anomalies, platelet dysfunction, and fibrinolysis. Bleeding and blood product transfusion is not uncommon during and after cardiac surgery.
While mild hemodilution can reduce blood viscosity and improve the cerebral blood flow, moderate-severe hemodilution can impair oxygen carrying capacity causing tissue ischemia. Therefore, depending on the patient’s age and comorbidities, an acceptable hematocrit levels during CPB is 18-30%. Cell salvaging allows for recovery of red blood cells by collecting and washing shed blood. Since platelets, coagulation protein, and inhibitors are lost during the cell-saver washing and extracorporeal circuit priming, transfusions may be required. Antifibrinolytic therapy can help prevent fibrinolysis and minimize transfusions.
In the intensive care unit (ICU), MOD is a prominent cause of morbidity and mortality after cardiac surgery [1]. MOD can significantly alter the patients morbidity, mortality, length of stay, mechanical ventilation days, and incidence of stroke, deep sternal wound infection, renal failure, and need for reoperation. As more organs become dysfunctional, the mortality rate rises. For example, the incidence of one organ dysfunction is 73.6%, which corresponds to a 21.1% mortality risk, while the incidence of developing ≥ 4 organs dysfunction is 1%, yet corresponds to a mortality risk of 76.2% [2]. In this chapter, we will discuss the epidemiology, etiology, diagnosis, and management of the major organ dysfunctions associated with cardiac surgery.
Pulmonary
Given the physiologic inter-dependence of the cardiac and pulmonary systems along with the uniform use of mechanical ventilation during and after thoracic surgery, respiratory impediments remain a prominent cause of morbidity, ICU length of stay (LOS), healthcare costs, and mortality after cardiac surgery [3]. Morbidity, LOS, and mortality six months post-cardiac surgery is greater in clinical situations where combined cardiac and respiratory failure occur (51%) as opposed to when respiratory failure alone is encountered (36%). Post-cardiac pulmonic complications can be related to a primary cardiac disorder (cardiogenic pulmonary edema, congestive heart failure), intrinsic pulmonary disorder (atelectasis, pneumonia, pulmonary embolism), or a complication of CPB (post-pump lung syndrome, acute respiratory distress syndrome). Post cardiac procedure complications may occur early (difficulty in liberating from the ventilator) or late (need for mechanical ventilation reinstitution), with the most common causes being; pneumonia (78%), cardiogenic pulmonary edema and adult respiratory distress syndrome (5%) [4]. Risk factors for pulmonary dysfunction that may lead to MOD have been well described, including [5]:
1. Preoperative variables:
a) age ≥ 75 years
b) body mass index ≥ 30 kg/m2
c) mean pulmonary artery pressure ≥ 20 mmHg
d) stroke volume index ≤ 30 mL/m2
e) low serum albumin
f) cerebrovascular disease
g) emergency surgery
h) CPB time ≥ 140 minutes
2. Postoperative variables include:
a) an immediate postoperative hematocrit < 30%
b) mean systemic arterial pressure < 90 mmHg
c) cardiac index < 3.0 L/min/m2
The principle cause of pulmonic complications after cardiac surgery is a low cardiac output (CO) state [6]. A reduction in CO can (1) increase pulmonary capillary pressure and subsequent positive fluid balance, resulting in cardiogenic pulmonary edema and congestive heart failure; (2) fatigue, which results in weakened cough, poor inspiratory efforts and lung mechanics attributing to atelectasis, pulmonary effusions, and/or pneumonia; (3) ≥ 50% reduction in FVC, FEV1, PEFR, and maximum voluntary ventilation (MVV) affecting rib cage expansion. FRC and FEV1 are more affected when internal mammary artery grafts are used rather than saphenous vein grafts [7].
While off-pump and on-pump surgery have similar affects on lung mechanics (FVC, FEV1), alveolar-arterial oxygen gradient, tissue elastance, and inspiratory resistance, patients who undergo on-pump surgery have substantial expansions in expiratory airway resistance [8]. There is less pain and time to return to baseline pulmonary function after ministernotomy or thoracoscopy as compared to median sternotomy, though no difference in mechanical ventilation days is seen [9]. On the contrary, minithoracotomies and thoracoscopy require one-lung ventilation, which may cause atelectasis during the deflated state of the non-ventilated left lung.
Reductions in pulmonic complications may be difficult to achieve, though efforts should be made to liberate patients from the ventilator earlier, improve oxygenation/ventilation, and encourage chest physiotherapy. Atelectasis, which leads to reduced PaO2 and functional lung volume, may be prevented via continuous positive airway pressure (CPAP) during CPB and positive end expiratory pressure (PEEP) immediately after CPB [10]. Recruitment maneuvers before stopping CPB reduces shunting, time to extubation by approximately 3 hours [11]. Noninvasive ventilation with conventional chest physiotherapy plus incentive spirometry after extubation can improve FRC, VC, FEV1 and PAO2 to preoperative levels.
Pleural effusions may be the first sign of impending respiratory failure and subsequent MOD. Effusions may be caused by bleeding, pneumonia, cardiogenic pulmonary edema, ARDS, pleurotomy, atelectasis, pleural lymphatic drainage disorder, leaking of mediastinal fluid, and/or chylothorax [12]. While most effusions resolve within a year, thoracentesis or chest tubes may be required depending on the size of the effusion and potential effects on respiratory performance. Pneumonia after cardiac surgery is a prominent cause of respiratory failure. The incidence may be higher if there is a history of smoking, chronic obstructive pulmonary disorder (COPD), failure to thrive, immunosuppression, atelectasis, aspiration, reintubation, presence of a nasogastric tube, transfusion of ≥ 4 units of blood products, and/or treatment with broad-spectrum antibiotics or H2-receptor blocking agents. Pneumonia after cardiac surgery can increase mortality dramatically because of the propensity for MOD. As each day of mechanical ventilation increases the risk of pneumonia by 1%, efforts should be made to liberate patients from the ventilator as early as possible [13]. Post-cardiac surgery pneumonia can be curtailed via using closed system suction catheters, continuous subglottic suctioning, maintaining semi-recumbence, early ambulation, and maintaining normoglycemia [14].
Cardiogenic pulmonary edema can increase the risk of MOD, therefore improving the underlying cardiac function with inotropic agents, afterload reduction, diuretics, and/or insertion of an intra-aortic balloon pump (IABP) should be considered. On-pump surgery causes a systemic inflammatory response that can lead to increased pulmonary endothelial permeability and subsequent non-cardiogenic pulmonary edema. Although ARDS after CPB only occurs in less than 2% of patients, the mortality rate can be as high as 80%, emphasizing the need for protective lung strategies in intubated patients after cardiac surgery [15].
Cardiac surgery can induce a hypercoagulable state, which can lead to thromboembolic events and subsequent MOD. The reported incidence of pulmonary embolism after cardiac surgery ranges from 0.3% to 9.5%, with an incidence of fatal pulmonary embolism of 0.5% [16]. Deep venous thrombosis prophylaxis should be initiated as soon as possible to reduce the incidence of venous thromboembolic events after cardiac surgery. Aspirin and elastic gradient compression stockings should be used in patients who ambulate within 2 to 3 days after surgery, while low-molecular-weight heparin and sequential compression stockings should be used in bedridden patients [17].
Cardiac
It is not surprising that cardiac dysfunction after cardiac surgery is a major cause of MOD. Postoperative cardiac complications may include bleeding, pericardial tamponade, arrhythmias, right and/or left ventricular failure, coronary vessel restenosis, valvulopathy, and the less frequently cardiac wall rupture and/or perforation. Both tachyarrhythmias and bradyarrhythmias represent a major cause of morbidity, increased LOS, economic burden, MOD, and mortality. Though atrial tachyarrhythmias (atrial fibrillation) is the most common arrhythmia after cardiac surgery, ventricular arrhythmias and conduction disturbances may also transpire [18]. Postoperative atrial fibrillation is typically self-limiting, but can require anticoagulation therapy and rate/rhythm control strategies. Sustained ventricular arrhythmia in the absence of a reversible cause(s) often warrants immediate attention and long-term preventive therapy. Transitory bradyarrhythmias can be managed with temporary pacing wires, though permanent pacing may be needed for significant and persistent atrioventricular block or sinus node dysfunction.
Several risk factors for postoperative cardiac complications that may lead to MOD have been described. An elevated preoperative brain natriuretic peptide plasma concentration is a predictor of postoperative cardiac dysfunction [19]. Increasing age correlates with postoperative cardiac dysfunction, in that the odds ratio for developing postoperative atrial fibrillation is 1.51 per decade [20]. Patients with structural heart disease, including atrial enlargement or elevation in atrial pressures, undergoing cardiac surgery have an increased predisposition to atrial tachyarrhythmias. Cardiomegaly can be attributed to a ventricular arrhythmogenic substrate. Prior arrhythmias (principally atrial fibrillation), cardiac surgery, congenital heart disease, right coronary or atrioventricular nodal artery disease, valvulopathy, obesity, cerebrovascular disease, and COPD represent other notable risk factors for cardiac dysfunction [21].
Intra-operative cardiac complications are a major cause of cardiac dysfunction. The trauma related to cardiac surgery can result in atrial and ventricular arrhythmias, pericarditis, and pericardial effusions. Perioperative hypoxia, hypercarbia, instrumentation, endogenous/exogenous catecholamines, acid-base disturbances, hypokalemia, hypomagnesemia, CBP time, and/or drug effects (i.e. cardiplegia) can cause cardiac ischemia.
Preoperative beta-adrenergic blockade and digoxin can reduce the rate of postoperative supraventricular arrhythmias [21,22]. Inotropic agents can be arrhythmogenic due to increase in sinoatrial node automaticity and decrease in AV nodal conduction time. Preservation of the anterior epicardial fat pad during cardiac surgery had been shown to reduce the risk of postoperative atrial fibrillation [23]. a transplanted heart may be subject to arrhythmogenesis and cardiac dysfunction to due to ischemia during organ preservation, organ rejection, atherosclerosis, denervation, or structural anomalies such as wide surgical suture lines [24].
Isolated premature ventricular complexes (PVC), typically related to metabolic imbalances, are common after cardiac surgery and rarely necessitate acute treatment or long-term antiarrhythmic therapy. Though frequent PVCs (>30 per hour) in a patient with impaired left ventricular and an ejection fraction <40% may lead to worsened ventricular function and subsequent higher risk of MODS or mortality. [25] In patients with hemodynamic compromise related to PVCs, lidocaine can be used for refractory PVCs after metabolic/electrolyte imbalance correction. Sustained ventricular arrhythmias, notably ventricular tachycardia (VT) and ventricular fibrillation (VFib) can occur, and accordingly redispose to MOD, as a result of hypoxia, hemodynamic instability, electrolyte disturbances, hypovolemia, medications (inotropes, antiarrhythmic agents), myocardial ischemia/infarction, infection, graft stenosis, and reperfusion after cessation of CPB. While asymptomatic non-sustained VT (NSVT) often do not merit therapy other than the correction of reversible causes, symptomatic NSVT can be managed with overdrive pacing, lidocaine, procainamide, or amiodarone [26]. Hemodynamically unstable sustained VT should be promptly chemically or electrically cardioverted. Refractory VT occuring in the immediate peri-operative periodor may necessitate initiation of emergent CPB on the short term and insertion of an implantable cardioverter-defibrillator for long term protection.
Neurologic
Though neurologic decline is often transient after cardiac surgery, persistent cognitive decline after an early improvement stage can suggest further neurologic dysfunction and subsequent MODS [27]. Despite advances in cardiac surgery, neurological complications, including ischemic stroke, delirium, and persistent cognitive decline, still commonly occur. Ischemic stroke is perhaps the most severe neurologic complication caused by perioperative cerebral thromboembolism or hypoperfusion injury. The incidence of cerebrovascular accidents after cardiac surgery has progressively declined to rates of 1-5% [28]. For patients with significant atherosclerotic vascular disease, assessment for carotid disease (i.e. carotid duplex screening) should be done prior to cardiac surgery and consideration for simultaneous or staged combined carotid and coronary revascularization should be sought in patients with symptomatic carotid disease.
Perioperative strokes can occur early (pre-extubation) or late (post-extubation) and can arise from different pathophysiological processes. Early or intraoperative cerebrovascular accidents can be due to peripheral and carotid vascular disease, prior cardiac surgery, low intraoperative mean arterial pressure, poor perioperative glycemic control, poor baseline clinical and/or cognitive condition, left ventricular dysfunction, carotid stenosis >70%, on-pump surgery, hypothermic circulatory arrest, preoperative creatinine elevation, atherosclerosis, increased CPB time, older age, and/or coagulopathy. Late or postoperative stroke can arise in patients with left main stenosis, diabetes, female sex, anemia, low body surface area, unstable angina, postoperative arrhythmia, sepsis, valvular surgery (9.7% for multivalve surgery versus 3.8% for CABG), or inotropic support. Post-cardiac surgery delirium is more likely to occur in the patients older than 65 years, postoperative or previous stroke, mechanical ventilation > 24 hours, postoperative renal insufficiency, blood product administration, concomitant CABG and valvular surgery, preoperative benzodiazepine use, female gender, history of depression, low education or baseline cognitive scores, and comorbidities [29].
Aspirin, if initiated within 48 h of revascularization, can reduce the incidence of perioperative stroke by 50% [30]. Preoperative statin therapy reduces the postoperative atrial fibrillation, LOS, stroke, cognitive dysfunction and mortality [31]. Although localized intra-arterial thrombolysis has been used safely in stroke patients after cardiac surgery, systemic thrombolysis should be avoided within 14 days [32]. Though evidence exists for the feasibility of therapeutic hypothermia in patients with stroke after cardiac surgery, its’ efficacy and safety has not been well studied. Efforts to reduce the incidence of delirium after cardiac surgery include neuroleptic prophylaxis (i.e. risperidone), use dexmedetomidine rather than benzodiazepines or propofol, sedation and neuromuscular blockade minimization, and early mobilization [33].
Gastrointestinal
Postoperative gastrointestinal (GI) complications after cardiac surgery, while rare, can result in rapid MOD and subsequent death in 17-50% of patients [34]. Gastrointestinal dysfunction can come in a variety of presentations, including intestinal bleeding or ischemia, pancreatitis, cholecystitis, hepatic failure, and ileus. The overall incidence of GI dysfunction is 0.3%-2%, with a consequential mortality ranging from 10%-60% usually secondary to MOD [35]. Research has allowed us to understand how GI dysfunction seem to all revolve around hypoperfusion.
Risk factors include age > 70 years, perioperative cardiac output failure, hypovolemic hypotension, prolonged CPB time, postoperative blood transfusions, need for emergency surgery or reoperation, triple-vessel disease, New York Heart Association functional class IV, inotropic support, arrhythmia, renal or hepatic failure, previous GI surgery, prolonged mechanical ventilation, peripheral vascular disease, and congestive heart failure. Numerous studies have reported the strong association between CPB time, renal dysfunction, and protracted ventilation with GI dysfunction after CABG, likely related to visceral vasoconstriction and subsequent splanchnic hypoperfusion. Counterpulsation via intra-aortic balloon pumps may result in atheroemboli in the extremities and viscera of patients with severe aortoiliac arteriosclerotic disease.
Hepatic blood flow is reduced by approximately 20% during CPB, more so especially during hypothermic temperatures (28-30 C) [36]. Interestingly, preoperative alcohol intake and elevated hepatic enzymes were not associated with an increased risk of hepatic failure after cardiac surgery, while elevated right atrial pressure, CPB time > 80 minutes, and multiple valve replacements were [37].
Measures to reduce GI dysfunction can occur preoperatively and postoperatively. Preoperatively, clinicians should identify severe abdominal aorta and secondary branch arteriosclerosis. Intraoperatively, avoidance of prolonged CPB, hypovolemic hypotension, and on-pump myocardial revascularization can help mitigate splanchnic perfusion. In patients with severe abdominal aortic disease, judicious use of vasoconstrictors and intra-aortic balloon pump counterpulsation should be considered. If at all possible, postoperative bleeding in high-risk patients should be managed with early re-exploration to avoid prolonged periods of hypotension and blood transfusions. If mechanical ventilation must be used, PEEP should be limited as it can induce angiotensin and catecholamine production, leading to splanchnic vasoconstriction [38]. Early liberation from the ventilator, IABP, vasopressors, and correction of arrhythmias can help reduce the complications related to GI dysfunction after cardiac surgery.
Renal
The incidence of post-cardiac surgery acute kidney injury (AKI) can range from 50% having mild AKI renal injury (creatinine rise <25%), 8-15% having moderate kidney injury, and 5% developing end-stage kidney injury and requiring dialysis [39]. AKI after cardiac surgery can lead to myocardial infarction, bleeding necessitating reoperation, infection, MOD, and mortality. Mortality is rare in patients with renal failure after cardiac surgery unless complicated by multiorgan failure or sepsis [40].
As with GI dysfunction, renal dysfunction after cardiac surgery is principally secondary to hypoperfusion which may occur during or after CPB. In additional, AKI after cardiac surgery can be related to nephrotoxic agents, atheromatous plaques, platelet aggregates, emboli, metabolic factors, neurohormonal activation, and/or oxidate stress. Risk factors include preoperative renal dysfunction, valvular surgery, IABP, need for reoperation, decreased ejection fraction or cardiac output, peripheral vascular disease, congestive heart failure, COPD, prolonged CPB time, severe hypertension or hypotension, advanced age, diabetes, on-pump surgery, preoperative hyperglycemia, sepsis, and anemia with need for blood product transfusion [41].
Renal dysfunction can be diagnosed by abnormal creatinine levels, low urine output, urinalysis including evaluation for casts, and/or novel biomarkers including neurotrophil-gelatinase-associated lipocalin and cystatin C [42]. Renal ultrasound can help assess for obstructive causes or renal artery stenosis. Nephrology evaluation should be considered in persistent, worsening or severe AKI to help assess further diagnostic testing.
Preventative strategies include adequate hydration, maintenance of normotension/ normoglycemia/ normothermia, sodium bicarbonate, and dopaminergic or diuretic drugs depending on the etiology [40]. Treatment involves treating the underlying cause, including cessation of nephrotoxins if possible, correction of metabolic disorders, normalization of blood pressure, and renal replacement therapy.
Hematologic
Hematologic dysfunction after cardiac surgery can be difficult to manage given the need for anticoagulation in the setting of normal homeostasis restoration. After CPB, hematologic dysfunction can include coagulation anomalies, platelet dysfunction, and fibrinolysis. Bleeding and blood product transfusion is not uncommon during and after cardiac surgery.
While mild hemodilution can reduce blood viscosity and improve the cerebral blood flow, moderate-severe hemodilution can impair oxygen carrying capacity causing tissue ischemia. Therefore, depending on the patient’s age and comorbidities, an acceptable hematocrit levels during CPB is 18-30%. Cell salvaging allows for recovery of red blood cells by collecting and washing shed blood. Since platelets, coagulation protein, and inhibitors are lost during the cell-saver washing and extracorporeal circuit priming, transfusions may be required. Antifibrinolytic therapy can help prevent fibrinolysis and minimize transfusions.
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