Show Summary Details
Page of

Perioperative management of the high-risk surgical patient: cardiac surgery 

Perioperative management of the high-risk surgical patient: cardiac surgery
Chapter:
Perioperative management of the high-risk surgical patient: cardiac surgery
Author(s):

Marco Ranucci

, Serenella Castelvecchio

, and Andrea Ballotta

DOI:
10.1093/med/9780199687039.003.0077_update_003

Update:

Minor updates throughout the text

References updated

Updated on 22 February 2018. The previous version of this content can be found here.
Page of

PRINTED FROM OXFORD MEDICINE ONLINE (www.oxfordmedicine.com). © Oxford University Press, 2016. All Rights Reserved. Under the terms of the licence agreement, an individual user may print out a PDF of a single chapter of a title in Oxford Medicine Online for personal use (for details see Privacy Policy and Legal Notice).

date: 17 October 2019

Summary

During the last decade, as a result of continually improving surgical strategy and the technology which supports it (e.g. anaesthesia), cardiac surgery is offered to patients with advanced age and those with increasingly complex co-existing conditions that were previously considered to be contraindications. In addition, an increasing number of patients have previously undergone angioplasty, thereby delaying their initial coronary artery bypass graft surgery to a more advanced age. In general, candidates for cardiac surgery may now be not only older than in the past, but also more likely to have health problems such as hypertension and diabetes. Risk stratification may help to identify ‘the’ high-risk patient: ‘pre-warned is pre-armed’.

In high-risk cardiac surgery patients, the surgical treatment options and perioperative care must be tailored to each patient, in order to optimize the benefits and minimize the risk of detrimental effects. The preoperative anticoagulation practice is an important aspect, balancing the risk between ischaemic and bleeding complications. New antiplatelet agents and oral anticoagulants have been recently delivered, and their role in patients scheduled for heart surgery is an additional important issue.

The high-risk cardiac surgery patient

Vital aspects of post-operative critical illness can often be forecast and ameliorated by appropriate preoperative assessments and interventions. Published estimates of the risk for an individual patient may aid the operator in selecting or avoiding specific devices or adjunctive pharmacotherapy; however, they are not substitutes for clinical judgement.

At present, the most used risk stratification models for the evaluation of procedural risk in cardiac surgery are the European System for Cardiac Operative Risk Evaluation score (EuroSCORE and EuroSCORE II; available at:  Perioperative management of the high-risk surgical patient: cardiac surgery <http://www.euroscore.org/calc.html>) [1, 2] and the STS (STSWebRiskCalc) score [3], both providing a web-based calculator. Recently, a parsimonious risk model for predicting the operative mortality risk in patients undergoing elective cardiac operations using only three variables was introduced [4]. This score is based on age, creatinine value, and EF (ACEF) and is calculated using the following formula:

Age ( years ) / ejection fraction ( % ) + 1 ( if creatinine > 2   mg / dL )

So far, validation has only been performed in elective patients where the score was shown to have similar sensitivity/specificity and similar positive/negative predictive values, compared to other risk models, including the additive/logistic EuroSCORE [5]. Recently, the ACEF score has been added to the CSS score for percutaneous catheter interventions [6]. The CSS demonstrated a higher accuracy in predicting mortality than the CSS or ACEF alone.

A recent update of the ACEF score (ACEF II) has been released [7]. With respect to the previous version, it includes emergency surgery and anemia within the risk factors.

The predictive accuracy of different risk scoring systems may be influenced by numerous factors such as differences in variable definitions, the management of incomplete data fields, surgical procedure selection criteria, and geographical differences in patient risk factors. An AUC of >0.7 is usually considered to be associated with a good predictive value. Predictive values for older scoring algorithms are usually poorer, when compared with more recent ones. Most algorithms overestimated the 30-day mortality in this patient population.

The new EuroSCORE II has similar accuracy and much better calibration than the EuroSCORE [8] and includes a number of new predictors. An important difference is that the EuroSCORE II is based on in-hospital mortality, rather than 30-day mortality. However, in a post hoc analysis, the authors could identify that 30-day and 90-day mortality rates are 0.6% and 1.5%, respectively, higher than the in-hospital mortality rate.

Patients at high risk for in-hospital mortality with percutaneous coronary intervention (PCI) most often are also high-risk for coronary artery bypass graft (CABG) [9]. The most important surgical risk groups are listed in  Perioperative management of the high-risk surgical patient: cardiac surgeryBox 77.1.

The emergent procedure(s)

Emergent surgical priority is associated with high risk within 7 days after surgery, but with subsequent rapidly decreasing risk over time. Patients with evolving non-ST-segment elevation acute coronary syndromes (NSTE-ACS) display a high-risk entity in CABG surgery. The higher rate of particular major morbidities is related to the processes of care before CABG (see  Perioperative management of the high-risk surgical patient: cardiac surgeryChapter 46) [10]. In the presence of refractory symptoms, haemodynamic alterations not responsive to standard treatment, or in ST-segment elevation myocardial infarction (STEMI) patients, emergency surgical therapy within the first few hours is indicated. Emergent CABG following primary PCI for ST-segment elevation myocardial infarction (STEMI) is consistently associated with higher mortality and a higher incidence of stroke, renal failure, and post-operative bleeding [11].

Balancing ischaemic and bleeding complications

About 10–15% of acute coronary syndrome (ACS) patients will require CABG during their hospitalization. In these patients, enhanced and irreversible platelet inhibition reduces ischaemic complications within 30 days but comes with a potential cost of increased bleeding [12]. The use of a P2Y12 receptor inhibitor, in combination with aspirin, within 5 days of CABG results in increased post-operative blood loss, increased use of blood products, and 10-fold increased re-exploration rates for bleeding [13]. In contrast, if CABG was delayed by ≥5 days, after stopping clopidogrel, bleeding was similar to that in those patients who had not received it [14].

Ticagrelor is a recent antiplatelet agent, acting on the P2Y2 receptor, reversible, and with a relatively short half-life. For anti-platelet agents, the following discontinuation times are needed before cardiac surgery (EACTS and ESC-EACTS guidelines) [15, 16]:

  • Acetylsalcilylic acid: continue until surgery, except in high-risk patients for surgical re-exploration and those who refuse transfusions

  • Prasugrel: 7 days

  • Clopidogrel: 5 days

  • Ticagrelor: 3 days

Point-of-care platelet function tests (PFTs) may eventually enable physicians to tailor antiplatelet therapy to the individual patient and to confirm that the antiplatelet effect is within the desired range [17, 18]. The recently released guidelines of the European Association of CardioThoracic Anaesthesiologists (EACTA) and European Association for Cardio-Thoracic Surgery (EACTS) include PFTs to establish the timing of surgery in patients under double antiplatelet therapy (class of evidence IIb) [19]

The risk of bleeding in patients undergoing emergency heart surgery under therapy with the direct oral anticoagulants (DOACs) (apixaban, rivaroxaban, dabigatran, epixaban) is not yet well established. Reversal of these agents may be difficult, but positive results have been reported for 4-factor prothrombin complex concentrates (PCCs) (rivaroxaban and apixaban) and factor VII inhibitor bypassing activity (dabigatran).

DOACs should be discontinued at least 48 hours before cardiac surgery, but a longer interval is required in patients with reduced renal function (class of evidence IIa) [19].

Recently, a specific antibody (idarucizumab) for fast reversal of dabigatran has been developed [20] and other specific antidotes are under deveopment.

Perioperative care

Very high-risk procedures are of course sometimes inevitable, because of the inherent risk of the underlying disease. A multidisciplinary approach to the care of the high-risk cardiac surgery patient is necessary, and a distinct care plan for these patients should be designed as soon as it is feasible. Many of these procedures are elective. However, even in the acute setting, the benefits of a specific procedure should be weighed against the risks involved, taking into account alternative treatment strategies, and the individual operators’ and the overall institution’s (surgical and intensive care team) experience! In some circumstances, a transfer to a major academic or high-volume centre that routinely performs complex surgical procedures may be the most effective and efficient course of action [21].

Haemodynamic monitoring

Background

The primary physiological task of the cardiorespiratory system is to deliver adequate O2 (DO2 = CaO2 × CO × 10) to meet the metabolic demands of the body (VO2). An increase in O2 demand is usually met by a combined increase in DO2 and O2 extraction ratio by the tissues (O2ER). An increase in DO2 can be accomplished by an increase in the cardiac output and the arterial O2 content CaO2 = (SaO2 × Hb × 1.39) + (0.031 × PaO2), where Hb is the haemoglobin level and SaO2 the arterial O2 saturation. Parameters reflecting a disturbance in the balance between O2 demand and DO2 (e.g. mixed venous saturation, lactate), both at global and regional levels, could be of value to optimize tissue O2 delivery. Manipulation of the cardiac output is a common clinical intervention.

Conventional haemodynamic monitoring for cardiac surgery patients includes the positioning of a pulmonary artery catheter (PAC), an arterial line on top of standard end-tidal CO2 and transcutaneous O2 saturation registration. Invasive haemodynamic and O2 monitoring identifies correctable physiological deficiencies in early stages. The purpose of monitoring is to obtain frequent, repetitive measurements of circulatory variables, in order to allow rapid recognition of circulatory problems, and to evaluate physiological conditions and the therapeutic effect of corrective therapy (see also  Perioperative management of the high-risk surgical patient: cardiac surgeryChapter 18).

Pulmonary artery catheter

In critically ill patients, the impact of PAC use on outcome is debated. Also in (high-risk) cardiac surgery, the implementation of PACs into the monitoring protocol is matter of personal preference, with supporters [22] and detractors [23]. The haemodynamic variables easily measured by a PAC include mixed venous O2 saturation (SvO2), cardiac output, right ventricular ejection fraction (RVEF) (with some catheters), and intrapulmonary vascular pressures. Clearly, newer monitoring devices, including oesophageal Doppler and arterial pulse contour analyses, can be used to measure cardiac output. However, none of these measure SvO2 or simultaneously assess the intrathoracic vascular pressure, factors that may determine treatment options. Recent advances in catheter technology have produced impressive novel and innovative uses of monitoring devices, requiring only central venous catheterization or central venous catheterization combined with arterial catheterization. Central venous fibreoptic technology also allows for the continuous measurement of superior vena caval O2 saturation as a surrogate marker of SvO2. Unfortunately, the central venous pressure (CVP) does not reliably reflect left-sided filling pressures nor predict the volume responsiveness; less invasive measurements of the cardiac output are often approximate, and ScvO2 is not a reliable reflection of SvO2.

Potential indications for the use of PAC in perioperative monitoring include [24]:

  1. 1. Patients with preoperatively severely depressed left ventricular (LV) systolic function (left ventricular ejection fraction (LVEF) ≤0.30–0.35)

  2. 2. Patients with LV diastolic dysfunction

  3. 3. Patients with impaired right ventricle (RV) function

  4. 4. Patients with acute ventricular septal defect (VSD)

  5. 5. Patients supported by an intra-aortic balloon pump (IABP) or other mechanical circulatory support (MCS).

Transoesophageal echocardiography

Trans-oesophageal echocardiography (TOE) (see  Perioperative management of the high-risk surgical patient: cardiac surgeryChapter 20) should not be considered as an alternative to PAC; both should be considered complementary. Each technique gives unique information and can guide diagnosis and therapy differently. Echocardiography is often limited by the quality of images (transthoracic) or patient comfort (transoesophageal) in the post-operative phase.

TOE provides a continuous intraoperative, but not post-operative, monitoring; it is a semi-quantitative tool, provides a comprehensive imaging of the heart chambers and valve function, and can be used to assess both systolic and diastolic function of both ventricles. With adequate calculations, TOE may provide an indirect pressure measurement (pulmonary artery pressure (PAP)) and an approximation of the cardiac output. Therefore, the information derived from these two devices is probably complementary, rather than alternative, and patients with perioperative heart failure should be monitored with both PAC and TOE.

In fact, all cardiac surgery operations may be considered an adequate scenario for the use of TOE.

Mixed venous oxygen saturation

Mixed venous oxygen saturation (SVO2) and its surrogate, central venous oxygen saturation (ScVO2) (measured at the level of the superior vena cava with standard central venous catheters) are indices that may represent the adequacy of oxygen delivery (DO2) with respect to the metabolic needs (VO2) (see  Perioperative management of the high-risk surgical patient: cardiac surgeryBox 77.2).

Blood lactate

When the DO2 is inadequate to sustain the O2 consumption (VO2), energy for cellular life is derived from anaerobic metabolism [25]. This generates blood lactate. Hyperlactataemia is a well-recognized index of inadequate cardiac output. Hyperlactataemia during and after cardio-pulmonary bypass (CPB) is associated with poor outcome in cardiac surgery, with increased morbidity and mortality rates [2628]. Blood lactate monitoring is valuable during perioperative heart failure. Increased values of blood lactate are a negative prognostic index, whereas stable and decreasing values may indicate that the cardiac output is recovering.

However, this monitoring should be seen within a comprehensive scenario of clinical evaluation, haemodynamic parameters, and potentially other measures of tissue perfusion. It is important to consider the potential limitations of lactate measurement in this setting:

  • Liver dysfunction. The accumulation of any metabolite is dependent on the balance between its production and elimination. Lactate overproduction is mainly the result of anaerobic production. Once lactate is formed, it is eliminated primarily (50%) by the liver, but the kidneys (25–30%), heart, and skeletal muscle are also involved, with variable kinetics. However, a certain time period for clearance is always required. Liver failure may contribute, but is probably not enough, to account for hyperlactataemia

  • Washout phenomenon. During (early) hypoperfusion, reduced blood flow may cause the sequestration of lactate in regional tissues. Late blood lactate increases, following cardiac operations, may be simply the expression of a reperfusion phenomenon

Pharmacological interventions

Myocardial protection

During cardiac operations, the heart is susceptible to various kinds of insult, and namely to ischaemic events and ischaemia–reperfusion injury. It is beyond the purpose of this chapter to address the myocardial protection techniques related to cardioplegia solutions and temperature management. In fact, there is still no general agreement on the best myocardial protection during aortic cross-clamping, and the technique of choice basically depends on the surgeon’s preferences. There is the possibility that some pharmacological strategies, targeting the principle of preconditioning, may be effective in exerting a myocardial protective effect [2931].

Blood glucose control

See  Perioperative management of the high-risk surgical patient: cardiac surgeryChapter 69.

Antiplatelet drugs

Therapy with antiplatelet agents, such as aspirin, started within 24 hours after CABG, reduces the risk of early occlusion of a saphenous vein graft and remains effective in reducing the risk of occlusion for 1 year, but not up to 3 years [32]. However, almost 50% of CABG patients had a previous infarction, and the benefit of aspirin in secondary prevention after an MI has been well established. Aspirin is a standard intervention for patients who have undergone CABG.

After cardiac surgery, aspirin should be (re)started as soon as there is no concern over bleeding, but within 24 hours of CABG and other cardiac surgeries in patients with a preoperative indication for aspirin (class of evidence I B/C) [15]

P2Y12 inhibitors should be re(started) as soon as there is no concern over bleeding, but within 48 hours from surgery in patients who received a coronary stent implantation within 1 month. In patients who received a coronary stent implantation (> 1 month before surgery) the therapy should be re-started within 96 hours from surgery. The same applies to patients who are operated after an acute coronary syndrome without stent implantation [15]

Non-pharmacological interventions

Surgical techniques

(See also  Perioperative management of the high-risk surgical patient: cardiac surgeryChapters 48 and 61.) Over the last two decades, interest has emerged in performing CABG without the use of CPB (off-pump), in order to reduce post-operative complications associated with the use of CPB. However, the short (before discharge or within 30 days after surgery) and long-term (beyond 12 months) benefit of off-pump surgery was questioned in a large randomized trial showing a significant increase in the primary short-term (death or complications of: reoperation, new mechanical support, cardiac arrest, coma, stroke, or renal failure) and primary long-term (death from any cause, repeat revascularization procedure, or a non-fatal myocardial infarction (MI)) composite endpoint. Similarly, off-pump coronary artery bypass graft (OPCABG) was not significantly different from on-pump CABG in neurocognitive outcomes [33]. The use of bilateral internal thoracic artery (ITA) vs single ITA for coronary artery revascularization did not show any advantage after a 1-year follow-up [34].

Cardiac assist devices, including the intra-aortic balloon pump

The IABP is a circulatory support device operating on the principle of counterpulsation, in which arterial diastolic and coronary perfusion pressures are augmented and the impedance to ventricular ejection (afterload) is reduced (see  Perioperative management of the high-risk surgical patient: cardiac surgeryChapters 30 and 31). IABP could be used preoperatively or in the peri-/post-operative period. The prophylactic insertion of an IABP in patients at high risk for post-operative heart failure is still the subject of a strong debate [35]. A very recent large RCT failed to demonstrate any benefit of prophylactic preoperative IABP use in stable coronary patients with reduced EF [36]. Its use in the setting of post-cardiotomy LV failure is much better established. Treatment success should be assessed after 60 min, based on simple haemodynamic parameters, including LA pressure (<15 mmHg), mixed venous saturation (SvO2 >60%), and diuresis (urine output >100 mL/hour).

Since IABP is incapable of supporting a patient with complete haemodynamic collapse and those suffering from low cardiac output syndrome, despite IABP support, immediate triage to more advanced percutaneous (or implantable) circulatory support modalities may be warranted to achieve circulatory recovery. Percutaneous MCS can be provided by a variety of devices and modalities designed to increase the forward blood flow and reduce filling pressures. A minimal flow rate of 70 mL/kg of body weight per minute is required to provide an adequate organ perfusion. Treatment options for MCS must be tailored to each patient, in order to optimize the benefits and minimize the risk of detrimental effects; access site complications are of particular concern.

Peri- and post-operative complications

Despite its proven benefits, cardiac surgery (e.g. CABG) can occasionally result in devastating or debilitating outcomes (see  Perioperative management of the high-risk surgical patient: cardiac surgeryTable 77.1). Some of these events represent a real challenge, due to either their relatively high incidence or their severe impact on mortality rate, and they will be specifically addressed in the following paragraphs.

Table 77.1 Morbidity after cardiac operations

Event

Reported operative rate (%)

Associated morality rate (%)

Bleeding-related surgical re-exploration

2–6

10–12

Perioperative myocardial infarction

5–20

6–8

Perioperative heart failure

10–40

20–25

Stroke

1–3

12–14

Neuropsychological dysfunction

20–70

Unchanged

Acute kidney injury

8–12

8–12

Acute renal failure (renal replacement therapy)

1–2

40–50

Acute respiratory distress syndrome

0.4–1

12–16

Mesenteric ischaemia/infarction

0.2–0.4

60–80

Gastrointestinal bleeding, pancreatitis, cholecystitis

0.1–0.2

40–50

Mediastinitis

2–3

10–25

Sepsis

1–2

30–40

Perioperative myocardial infarction

Perioperative MI occurs in 7–15% of patients after cardiac surgery and is associated with increased lengths of hospital stay, hospital costs, and reduced short- and long-term survival [37, 38]. MI is diagnosed with a combination of (markers of) myocardial necrosis (preferably troponin), in the presence of new clinical signs (e.g. an evolving ECG pattern which involves Q wave development) or symptoms of myocardial ischaemia [39,40]. The determination of perioperative MI within the first 72 hours after cardiac surgery may be problematic (type 5 of the third universal definition of myocardial infarction) [41]. Clinical symptoms are masked, while the patient is intubated, sedated, or under the intraoperative or post-operative effects of anaesthesia, and the sensitivity and specificity of post-operative ECG changes is poor. Periprocedural necrosis, within 72 hours post-CABG, is different from spontaneous infarction, as it may be associated with the instrumentation of the heart, coronary dissection, global or regional ischaemia related to an inadequate cardiac protection, microvascular events related to reperfusion, myocardial damage induced by O2 free radical generation, air embolism, or failure to reperfuse areas of the myocardium that are not subtended by graftable vessels [42].

cTnT and cTnI concentrations after CABG surgery are nearly universally elevated, are determined by numerous factors, and are independently prognostic of impending post-operative complications, when used at appropriate cut-points, while accounting for clinical risk [].Factors leading to periprocedural necrosis include the previously defined effects of direct myocardial trauma from sewing needles or manipulation of the heart, although thrombosis or stenosis of the graft or native network must be ruled out. Many of these complications are at least partially attributable to the process of atherosclerosis, thrombosis, and haemostasis. If outcomes among CABG patients are to be improved, the development of better strategies to reduce perioperative ischaemic events is imperative. cTnI and cTnT can both be used to indicate early myocardial damage, with their level correlating well with the level of injury.

Perioperative MI may result in a wide spectrum of clinical consequences, ranging from minor, non-haemodynamically relevant patterns to severe perioperative heart failure. An adequate assessment of the haemodynamic conditions should be performed immediately when suspecting a perioperative MI, through echocardiography, haemodynamic profile description, and coronary angiography (see  Perioperative management of the high-risk surgical patient: cardiac surgeryFigure 77.1). The treatment of MI is addressed in the recent ESC guidelines. These guidelines maintain their importance in the setting of perioperative MI following cardiac surgery [43] (see also  Perioperative management of the high-risk surgical patient: cardiac surgeryChapter X).


Figure 77.1 Algorithm. BiVAD, biventricular assist device; CI, cardiac index; ECMO, extracorporeal membrane oxygenation; EF, ejection fraction; IABP, intra-aortic balloon pump; LV, left ventricle; LVAD, left ventricular assist device; LVEDV, left ventricular end-diastolic volume; LVOT, left ventricular outflow tract; PAC, pulmonary artery catheter; PCWP, pulmonary capillary wedge pressure; RVOT, right ventricular outflow tract; SAM, systolic anterior motion; SBP, systolic blood pressure; TAPSE, tricuspid annular plane systolic excursion; TOE, transoesophageal echocardiography. GREEN: PAC-derived data. BLUE: TOE-derived data. YELLOW: diagnosis WHITE: Clinical signs and interventions.

Figure 77.1
Algorithm. BiVAD, biventricular assist device; CI, cardiac index; ECMO, extracorporeal membrane oxygenation; EF, ejection fraction; IABP, intra-aortic balloon pump; LV, left ventricle; LVAD, left ventricular assist device; LVEDV, left ventricular end-diastolic volume; LVOT, left ventricular outflow tract; PAC, pulmonary artery catheter; PCWP, pulmonary capillary wedge pressure; RVOT, right ventricular outflow tract; SAM, systolic anterior motion; SBP, systolic blood pressure; TAPSE, tricuspid annular plane systolic excursion; TOE, transoesophageal echocardiography. GREEN: PAC-derived data. BLUE: TOE-derived data. YELLOW: diagnosis WHITE: Clinical signs and interventions.

There are no well-defined algorithms to guide the treatment of perioperative MI. According to the haemodynamic consequences, the treatment can be conservative or require an early percutaneous or surgical revascularization. The risks and benefits of these strategies should be pondered on, in light of the infarction site and area, and, most importantly, of the haemodynamic consequences of the lesion.

  1. 1. Relief of pain, breathlessness, and anxiety. In patients under mechanical ventilation, oxygenation and the level of sedation must, however, be optimized

  2. 2. Haemodynamic stabilization. The heart function should be assisted with inotropic drugs (see  Perioperative management of the high-risk surgical patient: cardiac surgeryFigure 77.1); mechanical assistance of the failing heart with IABP may be indicated [44]. Ventricular assist devices may be considered when pharmacological therapy and the IABP cannot achieve a satisfactory haemodynamic response

  3. 3. Restoring coronary patency and myocardial tissue perfusion

  4. 4. Antithrombotic therapies. At all times, the risks of ischaemic complications should be balanced against the risk of major bleeding. Heparin treatment may be established and modulated, according to the activated coagulation time (ACT) and bleeding tendency of the patient

Heart failure

(See also  Perioperative management of the high-risk surgical patient: cardiac surgeryChapters 51, 52, 53, and 54.) Post-cardiotomy cardiogenic shock (CS) occurs in approximately 2–6% of patients who undergo open heart surgery. Perioperative heart failure is often a very complex entity, with multifactorial patterns that can involve different aspects of cardiac function, and may be isolated to the LV (24%) or RV (23%) or involve both sides of the heart (25%) [45]. Mechanical factors, as well as systolic and/or diastolic ventricular dysfunction, may be involved. In terms of predictors of major morbidity (including post-operative low cardiac output), NT-proBNP can play a major role in the setting of surgical LV restoration [46]. A diagnostic/therapeutic algorithm, based on PAC and TOE data, is shown in  Perioperative management of the high-risk surgical patient: cardiac surgeryFigure 77.1.

Respiratory failure

Respiratory failure is common (2–20%) and continues to be a major cause of potentially fatal morbidity after CABG. Respiratory function after CABG is readily influenced by the post-operative occurrence of extracardiac organ or system complications [47]. High-flow nasal oxygen is an innovative form of respiratory support but its routine use in cardiothoracic surgical patients remains controversial [48].

Acute renal failure

Severe acute kidney injury (AKI) is defined by the RIFLE and KDIGO criteria [49,50], as a peak post-operative creatinine value doubles the baseline value and is sustained for >24 hours within the first 72 post-operative hours, with a urine output of <0.5 mL/kg/hour for at least 12 hours (see  Perioperative management of the high-risk surgical patient: cardiac surgeryChapters 29 and 68). Acute renal failure is a more severe condition, often requiring renal replacement therapy (RRP). Even if other biomarkers (NGAL) may provide an earlier detection of post-operative AKI, the clinical diagnosis and staging of AKI is still based on creatinine-derived criteria.

Following cardiac surgery, AKI may be present in about 10% of the population, whereas acute renal failure (ARF) requiring RRT has an incidence of 1–2% and is accompanied by a mortality rate of about 50% [5154]. The occurrence of post-operative renal failure has risen over the past decade, and most dramatically for those patients undergoing emergency CABG within 24 hours of an MI. Independent predictors of acute renal failure with RRT are listed in  Perioperative management of the high-risk surgical patient: cardiac surgeryBox 77.3.

Specific aspects of AKI and acute renal failure in the cardiac surgery setting rely mainly on the optimization of the circulating volume and renal perfusion pressure, especially in cases of perioperative heart failure: the limitation of inotropic and vasoconstrictive agents to the lowest possible amount capable of ensuring an adequate cardiac output and perfusion pressure; a fluid intake modulated on the basis of the urine output; restriction of K+ intake; the discontinuation of nephrotoxic drugs and dose adjustments of drugs being metabolized by the kidney.

Mesenteric ischaemia and infarction

Although being rare complications (0.2–0.5%), mesenteric ischaemia and infarction following cardiac surgery are severe events, associated with a mortality rate that exceeds 70% [55, 56]. Risk factors for mesenteric infarction include older age, patients with arteritis, intraoperative hypoperfusion, emergency operation, longer CPB time, need for high-dose vasopressor, IABP, and valve operations [57]. The pathogenesis of acute mesenteric infarction may be related to a poor perfusion during CPB [5658]. Alternatively, mesenteric infarction may result from an acute perioperative thromboembolic event. This event is more common in patients with a prothrombotic state (history of smoking or COPD) or a tendency to develop embolic events (heparin-induced thrombocytopenia (HIT), AF, and preoperative hyperhomocysteinaemia) [55, 59].

The GICS score [60] is a scoring model for all gastrointestinal (GI) complications after cardiac surgery—age >80 years, preoperative inotropic support, NYHA class III and IV, CPB >150 minutes, post-operative atrial fibrillation, heart failure, vascular complication, and reoperation for bleeding are the variables included in the model. The GICS score is predictive for intestinal ischaemia alone, with an ROC of 0.87 [61].

Non-occlusive mesenteric ischaemia (NOMI) has been confirmed to be a common pattern of GI complications [62]. Arterial angiography can be performed when NOMI is suspected [63], associated with possible treatment with intra-arterial infusion of vasodilators [64]. Non-occlusive mesenteric ischaemia (NOMI) causes maldistribution or reduction of splanchnic blood flow and is actually a serious complication after cardiac surgery with a mortality rate above 90%. A recent paper reported patients with NOMI had significantly higher values of procalcitonin, a peptide secreted by thyroid parafullicular cells, which is a well known marker of sepsis and septic shock [65].

The diagnosis of mesenteric infarction in cardiac surgery patients may be cumbersome and may be triggered by hyperlactataemia. CT scan can be of help. Early laparotomy should be considered whenever acute mesenteric infarction is highly suspected [56].

Among the GI complications after cardiac surgery, the presence of liver cirrhosis (LC) is strongly associated with a high risk of morbidity and mortality. The prevalence of LC in patients undergoing cardiac surgery is reported to be 0.2–0.3%. The Child–Pugh (CP) score is widely accepted for the clinical assessment of LC patients. A recent review of 19 papers applying the CP score showed that overall 30-day mortality of cirrhotic patients has been 19.3% [66]. But with grading the patients into three groups, according to the sum of the score (class A 5–6; class B 7–9; class C 10–15), mortality was 9%, 37.7%, and 52% at 1 month, and 27.2%, 66.2%, and 78.9% at 1 year, respectively, for each group [66].

Bleeding and transfusion

Cardiac surgery patients may experience excessive post-operative bleeding, due to a number of factors (the preoperative use of antiplatelet agents, CPB-induced platelet dysfunction, consumption of coagulation factors, hyperfibrinolysis). The incidence of severe bleeding in cardiac surgery exceeds 10%, and 5–7% of these patients experience blood loss in excess of 2 L within the initial 24 hours after surgery [67].

As a consequence, allogeneic blood transfusions may be necessary, and, in a certain percentage of patients (2–5%), surgical re-exploration is needed. Both these factors have deleterious effects on the quality of post-operative recovery. Transfusions are associated with an increased morbidity and mortality rate in retrospective studies [67], and surgical re-exploration is associated with a 3-fold increase of major complications and a 4-fold increase in operative mortality [68]. In patients undergoing cardiac surgery, leucocyte-depleted; red blood cells should be preferred, when available [68]. In general, there is no benefit from transfusion for haematocrits as low as 21% (haemoglobin of 7 g/dL); however, patients with haemodynamic instability and with organ ischaemia may benefit from higher haematocrit values (up to 30%). Recently, two RCTs have challenged the concept that restrictive transfusion policies may be beneficial in cardiac surgery patients. The TITRe2 study [69] found no differences in the primary outcome (major morbidity) between patients treated according to a liberal (trigger haemoglobin value 9.0 g/dL) or restrictive (trigger haemoglobin value 7.5 g/dL) transfusion protocol. However, patients in the restrictive group had a higher mortality at 3-month follow-up (4.2% vs 2.6%; hazard ratio 1.64; 95% CI 1.00–2.67; P = 0.045). A post hoc analysis of the TRACS study demonstrated that elderly patients treated according to a restrictive transfusion policy had a significantly higher rate of post-operative cardiogenic shock than patients treated according to a liberal transfusion strategy (12.8% vs 5.2%, P = 0.031) [70]. Stored red blood cells are 2,3-diphosphoglycerate–deficient, and consequently less adept at unloading O2 and less deformable, possibly leading to sludging and capillary occlusion.

Every effort should be exerted in order to limit post-operative bleeding [71]. The most obvious, and probably the most effective, strategy is to improve surgical techniques and ruling out abnormalities of haemostasis (see also  Perioperative management of the high-risk surgical patient: cardiac surgeryChapter 73). The approach to a patient with severe post-operative bleeding may be guided by specific algorithms based on POCTs [19]. These tests include TE and platelet function analysis. Different algorithms have been proposed [72, 73] and may be useful for suggesting the use of drugs, fresh frozen plasma, and platelet concentrates, as well as for deciding to surgically re-explore the patient.

Cases of excessive blood loss, in which no surgical cause or abnormalities in haemostasis can be identified, may require pharmacological strategies, which can be divided broadly into preoperative prophylaxis for operations that confer a high risk of bleeding and interventions for massive, refractory bleeding. The medications that have been most extensively evaluated as haemostatic agents include the antifibrinolytic lysine analogues aminocaproic acid and tranexamic acid, fibrinogen concentrate, PCCs, and desmopressin (a synthetic analogue of antidiuretic hormone (ADH) that increases the plasma levels of factor VIII and vWF) [7479]. In addition, recombinant activated factor VII appears to be efficacious in an array of clinical situations associated with life-threatening haemorrhage [80, 81]. Thrombotic complications constitute a major concern of agents that potentiate haemostasis, and namely of recombinant activated factor VII.

Atrial fibrillation and supraventricular arrhythmia

Atrial fibrillation (AF) is the most common arrhythmia to occur after cardiac surgery (see also  Perioperative management of the high-risk surgical patient: cardiac surgeryChapter 56). The incidence of AF has been reported to range between 20% and 40%, depending on the risk profile and type of surgery [8284]. Most events occur within 6 days post-intervention. It is associated with increased morbidity, including an increased risk of stroke (and decreasing their quality of life) and need for additional treatment with prolonged hospital stay, and increased health care resources [85, 86]. In addition to the expected demographic factors (age, male gender, diabetes, history of AF, history of congestive heart failure, hypertension, COPD, and a pre-CPB heart rate of >100 beats/min), certain surgical practices increase the risk of post-operative AF [87]. Preoperative treatment with β‎-blockers is the first choice in the prevention of post-operative AF. Also the use of either an oral or IV load of amiodarone chlorhydrate (Cordarone®) before surgery has been shown to decrease the post-operative risk of AF and proven cost-effective in the high clinical risk cohort [8891]. N-3 polyunsaturated fatty acids were deemed to have antiarrhythmic effects; a recent updated systematic review and a meta-analysis of randomized clinical trials do not support the usefulness of N-3 polyunsaturated fatty acids in preventing AF after cardiac surgery [92]. When β‎-blockers are contraindicated, amiodarone pre-treatment is recommended. Magnesium and K+ levels should be monitored and maintained during the early post-operative course [93]. Vernakalant, a new IV antiarrhythmic agent, can be considered as a safe and effective pharmacological alternative for the conversion of AF ≤ 3 days after cardiac surgery [94], but it should be avoided in haemodynamically unstable patients [95]. The combination of vernakalant and flecainide seems to improve the conversion rate in sinus rhythm in post-cardiotomy patients with post-operative AF (new-onset) and substantially preserved left ventricular systolic function, and it might act as an effective preconditioner for electrical cardioversion [96]. Rate control may be a challenge in the post-operative setting where adrenergic stress (either endogenous or secondary to inotropic drug use) is present. Short-acting β‎-blockers, such as esmolol, may be used when haemodynamic instability is present. Atrial fibrillation after cardiac surgery may increase morbidity (hospitalization) and mortality (death). Rate control has been shown to have similar rates of complications, length of in-hospital stay, and of persistent atrial fibrillation if compared with rhythm control strategies [97].

Direct current cardioversion may be required, especially in the early phases after the operation, when AF affects the patient haemodynamics [98, 99]. Surgical ablation improves the likelihood of sinus rhythm post-operatively, but the higher prevalence of sinus rhythm did not translate into improved clinical outcome at 1 year [100].

Usually anticoagulation is instituted for prolonged (>48 hours) duration of post-operative AF and/or for frequent episodes. The American College of Chest Physicians recommends the use of anticoagulation therapy, especially for high-risk patients (those with a history of stroke and/or transient ischaemia attacks). It is also recommended to maintain anticoagulation until 1 month after the post-operative AF episode [101]. Non-vitamin K oral anticoagulants (NOAC) are a solid alternative to vitamin K antagonists. There is a lack of data in early atrial fibrillation after cardiac surgery. In a recent survey by the European Heart Rhythm Association, 25% of the centres never used NOAC in post-cardiac surgery, 56 % reported implementation of NOAC without low-molecular weight heparin (LMWH) within 48 h, and the majority reported use post-surgery; less than 20% used NOAC with LMWH bridging [102].

The duration of post-operative AF after cardiac surgery is associated with worsened long-term survival [103]. In this context, dexmedetomidine sedation has been proposed after cardiac surgery as a substitute for propofol; a recent trial showed a reduction of the incidence of post-operative atrial fibrillation [104].

A recent prospective randomized controlled trial showed that prophylactic amiodarone reduces arrhythmia recurrence after surgical ablation within the first 3 months [105].

Stroke

Stroke following cardiac surgery is a relatively frequent (up to 2%) complication and long-term problem with important psychological impact for the patient [3] (see also  Perioperative management of the high-risk surgical patient: cardiac surgeryChapter 67). Many risk factors have been identified for the development of stroke in cardiac operations: age, history of cerebrovascular disease, peripheral vascular disease, diabetes, hypertension, previous cardiac surgery preoperative infection, active endocarditis, urgent operation, prolonged CPB time, transfusions, acute renal failure, low cardiac output syndrome, and AF [106108]. The single most important cause of stroke is aortic atheromatous disease, which is detected with high reproducibility by intraoperative TOE or epiaortic scanning. Patients with large (>5 mm) or mobile aortic atheromas have an increase in the rate of perioperative stroke by a factor of 5–10 and are likely to have a significantly increased long-term risk of stroke [109]. This finding highlights the role of surgical manoeuvres on the ascending aorta in the determining of early post-operative stroke [110]. Re-exploration for bleeding after cardiac surgery carries a significant risk of stroke [111]. The need for blood products, platelets, and fresh frozen plasma, in particular, seems to have a large impact on the development of stroke [112]. Treatment of perioperative stroke in cardiac surgery does not differ from the usual management of stroke.

Left atrial appendage closure at the time of cardiac surgery seems to reduce the incidence of early post-operative cerebrovascular accidents in patients with low CHAD2DS2-VASc score [113].

Delirium

Post-operative delirium may be a manifestation of an unrecognized preoperative disease or the results of intra-post-operative events [114] (see also  Perioperative management of the high-risk surgical patient: cardiac surgeryChapter 74). A recent review focused on the risk factors for post-operative delirium after on-pump cardiac surgery. Age, previous psychiatric conditions, cerebrovascular disease, and pre-existing cognitive impairment are strongly associated with post-operative delirium [115]. An excessive administration of anaesthetic drugs during surgery is another possible cause. Post-operative delirium may be a strong complication after cardiac surgery. The incidence of post-operative delirium has been reported to be between 20% and 50% in patients undergoing cardiac surgery, with elderly patients at the greatest risk; haloperidol, midazolam, and propofol have been the drugs more commonly administered to prevent and control post-operative delirium and to maintain sedation [116].

Some papers are supporting the use of dexmedetomidine, a centrally acting alpha-2 adrenergic receptor agonist in post-operative sedation protocols, with the aim of a reduction of the rate of delirium after cardiac surgery [117]. Recently, dexmedetomidine, an α‎2 adrenergic receptor agonist, has proven to be superior if compared with propofol in the reduction of the incidence, delayed onset, and shortened duration of post-operative delirium after cardiac surgery [118].

Peri- and post-operative complications in the elderly

Patients aged >80 years have little tolerance for any post-operative complication [119]. Mortality rises in the presence of acute renal failure (from 7.5% to 55%), low cardiac output syndrome (from 8.8% to 43.8%), sepsis (from 10.3% to 52%), prolonged respiratory failure with tracheotomy (from 11% to 29 %), re-thoracotomy due to bleeding (from 10.6% to 26.9 %), and post-operative laparotomy.

Personal perspective

Haemostatic balance before and after cardiac operations is placed in a strategic position for the outcome of the patients. The great majority of post-operative complications are either of a haemorrhagic or prothrombotic nature (and sometimes both). CABG patients are now extensively treated with single, double, and even triple anti-aggregation, and the new generation of platelet inhibitors (prasugrel/ticagrelor) is associated with an increased perioperative bleeding tendency. DOACs could increase this tendency when an emergency operation is required. However, the patient’s response to these drugs is highly subjective, and the classically suggested withdrawal time may not be sufficient for many of them to restore an adequate platelet function. Point-of-care platelet function tests are presently widely available, but we still lack standard values and well-defined cut-off values to decide whether or not to postpone surgery. This will be certainly a good matter for future clinical research. At the same time, post-operative complications related to thromboembolic events may account for up to 5–10% of the morbidity. In this setting, it is still unclear about the possible role of natural endothelial-derived anticoagulants (antithrombin, C-protein complex) that are extensively consumed during the operation but that are rarely measured and even more rarely replenished. Finally, the role of transfusions as determinants of bad outcomes is still debated. Massive blood transfusions are probably associated with a worse outcome; however, too restrictive transfusion policies may be associated with bad outcomes, due to peripheral organ dysoxia, especially in the elderly patients. In any case, a rational approach to bleeding should follow point-of-care-based algorithms. Further studies incorporating the new platelet function tests within the existing algorithms are highly suggested, in order to rationalize the use of allogeneic blood and derivatives.

Further reading

Murphy GJ, Pike K, Rogers CA, et al. Liberal or restrictive transfusion after cardiac surgery. N Engl J Med 2015; 372: 997–1008.Find this resource:

Nagaoka E, Arai H, Tamura K, Makita and Miyagi N. Prevention of atrial fibrillation with ultra-low dose landiolol after off-pump coronary artery bypass grafting. Ann Thorac Cardiovasc Surg 2014; 20: 129–34.Find this resource:

Nashef SA, Roques F, Sharples LD, et al. EuroSCORE II. Eur J Cardiothorac Surg 2012; 41: 734–44.Find this resource:

Ranucci M, Pistuddi V, Scolletta S, de Vincentiis C, Menicanti L. The ACEF II risk score for cardiac surgery: updated, but still parsimonious. Eur Heart J 2017, doi: 10.1093/eurheartj/ehx228.Find this resource:

Valgimigli M, Bueno H, Byrne RA, Collet JP, Costa F, Jeppsson A, Jüni P, Kastrati A, Kolh P, Mauri L, Montalescot G, Neumann FJ, Petricevic M, Roffi M, Steg PG, Windecker S, Zamorano JL. 2017 ESC focused update on dual antiplatelet therapy in coronary artery disease developed in collaboration with EACTS: The Task Force for dual antiplatelet therapy in coronary artery disease of the European Society of Cardiology (ESC) and of the European Association for Cardio-Thoracic Surgery (EACTS). Eur Heart J 2017; 2017 Aug 26. doi: 10.1093/eurheartj/ehx419.Find this resource:

2017 EACTS/EACTA Guidelines on patient blood management for adult cardiac surgery: The Task Force on Patient Blood Management for Adult Cardiac Surgery of the European Association for Cardio-Thoracic Surgery (EACTS) and the European Association of Cardiothoracic Anaesthesiology (EACTA). Eur J Cardiothorac Surg (in press).Find this resource:

Ibanez B, James S, Agewall S, Antunes MJ, Bucciarelli-Ducci C, Bueno H, Caforio ALP, Crea F, Goudevenos JA, Halvorsen S, Hindricks G, Kastrati A, Lenzen MJ, Prescott E, Roffi M, Valgimigli M, Varenhorst C, Vranckx P, Widimský P. 2017 ESC Guidelines for the management of acute myocardial infarction in patients presenting with ST-segment elevation: The Task Force for the management of acute myocardial infarction in patients presenting with ST-segment elevation of the European Society of Cardiology (ESC). Eur Heart J. 2017 Aug 26. doi: 10.1093/eurheartj/ehx393.Find this resource:

Thygesen K, Alpert JS, White HD, et al., the Writing Group on behalf of the Joint ESC/ACCF/AHA/WHF Task Force for the Universal Definition of Myocardial Infarction Third universal definition of myocardial infarction. Eur Heart J 2012; 33: 2551–67.Find this resource:

Ad-hoc working group of ERBP, Fliser D, Laville M, Covic A, Fouque D, Vanholder R, Juillard L, Van Biesen W. A European Renal Best Practice (ERBP) position statement on the Kidney Disease Improving Global Outcomes (KDIGO) clinical practice guidelines on acute kidney injury: part 1: definitions, conservative management and contrast-induced nephropathy. Nephrol Dial Transplant. 2012; 27: 4263–72.Find this resource:

Endo D, Kato TS, Iwamura T, Oishi A, Yokoyama Y, Kuwaki K, Inaba H, Amano A. The impact of surgical left atrial appendage amputation/ligation on stroke prevention in patients undergoing off-pump coronary artery bypass grafting. Heart Vessels. 2017; 32: 726–34.Find this resource:

References

1. Nashef SAM, Roques F, Michael P, Gauducheau E, Lemeshow S, Salamon R European system for cardiac operative risk evaluation (EuroSCORE) Eur J Cardiovasc Surg 1999; 16: 9–13.Find this resource:

2. Nashef SA, Roques F, Sharples LD, Nilsson J, Smith C, Goldstone AR, Lockowandt U. EuroSCORE II. Eur J Cardiothorac Surg. 2012; 41: 734–44.Find this resource:

3. Shroyer AL, Grover FL, Edwards FH 1995 Coronary artery bypass risk model: the Society of Thoracic Surgeons Adult Cardiac National Database. Ann Thorac Surg. 1998; 65: 879–84.Find this resource:

4. Ranucci M, Castelvecchio S, Menicanti L, Frigiola A, Pelissero G Risk of assessing mortality risk in elective cardiac operations: age, creatinine, ejection fraction, and the law of parsimony. Circulation 2009 23; 119: 3053–61.Find this resource:

5. Ranucci M, Castelvecchio S, Conte M, Megliola G, Speziale G, Fiore F, Guarracino F, Scolletta S, Escobar RM, Falco M, Bignami E, Landoni G The easier, the better: age, creatinine, ejection fraction score for operative mortality risk stratification in a series of 29,659 patients undergoing elective cardiac surgery. J Thorac Cardiovasc Surg 2011; 142: 581–86.Find this resource:

6. Garg S, Sarno G, Garcia-Garcia HM, Girasis C, Wykrzykowska J, Dawkins KD, Serruys PW; ARTS-II Investigators. A new tool for the risk stratification of patients with complex coronary artery disease: the Clinical SYNTAX Score. Circ Cardiovasc Interv 2010 3: 317–26.Find this resource:

7. Ranucci M, Pistuddi V, Scolletta S, de Vincentiis C, Menicanti L. The ACEF II risk score for cardiac surgery: updated, but still parsimonious. Eur Heart J 2017, doi: 10.1093/eurheartj/ehx228.Find this resource:

8. Di Dedda U, Pelissero G, Agnelli B, De Vincentiis C, Castelvecchio S, Ranucci M. Accuracy, calibration and clinical performance of the new EuroSCORE II risk stratification system. Eur J Cardiothorac Surg. 2013; 43: 27–32.Find this resource:

9. Singh M, Gersh BJ, Li S, Rumsfeld JS, Spertus JA, O’Brien SM, Suri RM, Peterson ED Mayo Clinic Risk Score for percutaneous coronary intervention predicts in-hospital mortality in patients undergoing coronary artery bypass graft surgery. Circulation. 2008; 117: 356–62.Find this resource:

10. Lincoff AM, LeNarz LA, Despotis GJ, et al. Abciximab and bleeding during coronary surgery: results from the EPILOG and EPISTENT trials. Improve Long-term Outcome with abciximab GP IIb/IIIa blockade. Evaluation of Platelet IIb/IIIa Inhibition in STENTing Ann Thorac Surg 2000; 70: 516–26.Find this resource:

11. Moscucci M, O’Donnell M, Share D, et al. Frequency and prognosis of emergency coronary artery bypass grafting after percutaneous coronary intervention for acute myocardial infarction Am J Cardiol 2003; 92: 967–69.Find this resource:

12. Ebrahimi R, Dyke C, Mehran R, et al. Outcomes following pre-operative clopidogrel administration in patients with acute coronary syndromes undergoing coronary artery bypass surgery: the ACUITY (Acute Catheterization and Urgent Intervention Triage strategY) trial J Am Coll Cardiol 2009; 53: 1965–72.Find this resource:

13. Hongo RH, Ley J, Dick SE, Yee RR The effect of clopidogrel in combination with aspirin when given before coronary artery bypass grafting. J Am Coll Cardiol 2002; 40: 231–37.Find this resource:

14. Berger JS, Frye CB, Harshaw Q, Edwards FH, Steinhubl SR, Becker RC Impact of clopidogrel in patients with acute coronary syndromes requiring coronary artery bypass surgery J Am Coll Cardiol 2008; 52: 1693–1701Find this resource:

15. 2017 EACTS Guidelines on perioperative medication in adult cardiac surgery. Eur J Cardiothorac Surg (in press)Find this resource:

16. Valgimigli M, Bueno H, Byrne RA, Collet JP, Costa F, Jeppsson A, Jüni P, Kastrati A, Kolh P, Mauri L, Montalescot G, Neumann FJ, Petricevic M, Roffi M, Steg PG, Windecker S, Zamorano JL. 2017 ESC focused update on dual antiplatelet therapy in coronary artery disease developed in collaboration with EACTS: The Task Force for dual antiplatelet therapy in coronary artery disease of the European Society of Cardiology (ESC) and of the European Association for Cardio-Thoracic Surgery (EACTS). Eur Heart J 2017; 2017 Aug 26. doi: 10.1093/eurheartj/ehx419.Find this resource:

17. Ranucci M, Baryshnikova E, Soro G, Ballotta A, De Benedetti D, Conti D; Surgical and Clinical Outcome Research (SCORE) Group. Multiple electrode whole-blood aggregometry and bleeding in cardiac surgery patients receiving thienopyridines. Ann Thorac Surg 2011; 91: 123–29.Find this resource:

18. Di Dedda U, Ranucci M, Baryshnikova E, Castelvecchio S; for the Surgical and Clinical Outcome Research (SCORE) Group. Thienopyridines resistance and recovery of platelet function after discontinuation of thienopyridines in cardiac surgery patients. Eur J Cardiothorac Surg 2013; 45: 165–70.Find this resource:

19. 2017 EACTS/EACTA Guidelines on patient blood management for adult cardiac surgery: The Task Force on Patient Blood Management for Adult Cardiac Surgery of the European Association for Cardio-Thoracic Surgery (EACTS) and the European Association of Cardiothoracic Anaesthesiology (EACTA). Eur J Cardiothorac Surg (in press).Find this resource:

20. Pollack CV Jr, Reilly PA, Eikelboom J, et al. Idarucizumab for Dabigatran Reversal. N Engl J Med 2015; 373: 511–20.Find this resource:

21. Birkmeyer JD, Stukel TA, Siewers AE, Goodney PP, Wennberg DE, Lucas FL Surgeon volume and operative mortality in the United States. N Engl J Med 2003; 349: 2117–27.Find this resource:

22. Vincent JL, Pinsky M Let us use the pulmonary artery catheter correctly and only when we need it. Crit Care 2005; 33: 119–1122.Find this resource:

23. Connors AF, Speroff T, Dawson NV, Thomas C, Harrel FE Jr, Wagner D, Desbiens N, Goldman L, Wu AW, Califf RM, et al. The effectiveness of right heart catheterization in the initial care of critically ill patients. JAMA 1996; 276: 889–97.Find this resource:

24. Ranucci M Which cardiac surgical patients can benefit from placement of a pulmonary artery catheter? Crit Care 2006; 10 (suppl 3): S6 doi:10.1186/cc4833Find this resource:

25. Rashkin MC, Bosken C, Baughman RP Oxygen delivery in critically ill patients. Relationship to blood lactate and survival. Chest 1985, 87: 580–4.Find this resource:

26. Maillet J-M., Le Besnerais P, Cantoni M, Nataf P, Ruffenach A, Lessana A, Brodaty D Frequency, risk factors, and outcome of hyperlactatemia after cardiac surgery. Chest 2003; 123: 1361–6.Find this resource:

27. Demers P, Elkouri S, Martineau R, Couturier A, Cartier R Outcome with high blood lactate levels during cardiopulmonary bypass in adult cardiac surgery. Ann Thorac Surg 2000; 70: 2082–6.Find this resource:

28. Ranucci M, De Toffol B, Isgrò G, Romitti F, Conti D, Vicentini M Hyperlactatemia during cardiopulmonary bypass: determinants and impact on postoperative outcome. Crit Care 2006; 10: R167 doi:10.1186/cc5113Find this resource:

29. De Hert SG, Cromheecke S, ten Broecke PW, Mertens E, De Blier IG, Stockman BA, Rodrigus IE, Van der Linden PJ Effects of propofol, desflurane, and sevoflurane on recovery of myocardial function after coronary surgery in elderly high-risk patients. Anesthesiology 2003 99: 314–23.Find this resource:

30. De Hert SG, ten Broecke PW, Mertens E, Van Sommeren EW, De Blier IG, Stockman BA, Rodrigus IE Sevoflurane but not propofol preserves myocardial function in coronary surgery patients. Anesthesiology. 2002; 97: 42–49.Find this resource:

31. Du Toit EF, Muller CA, McCarthy J Opie, LH Levosimendan: effects of a calcium sensitizer on function and arrhythmias and cyclic nucleotide levels during ischemia/reperfusion in the Langendorff-perfused guinea pig heart. J Pharmacol Exp Ther 1999; 290: 505–14.Find this resource:

32. Goldman S, Copeland J, Moritz T, et al. Long-term graft patency (3 years) after coronary artery surgery: effects of aspirin: results of a VA Cooperative study. Circulation 1994; 89: 1138–43Find this resource:

33. Shroyer AL, Grover FL, Hattler B, et al. On-pump versus off-pump coronary-artery bypass surgery. N Engl J Med 2009; 361: 1827–37.Find this resource:

34. Taggart DP, Altman DG, Gray AM, Lees B, Nugara F, Yu L-M., Campbell H, Flather M on behalf of the ART Investigators. Randomized trial to compare bilateral vs. Single internal mammary coronary artery bypass grafting: 1-year results of the Arterial Revascularisation Trial (ART). Eur Heart J 2010; 31: 2470–81.Find this resource:

35. Holman WL, Li Q, Kiefe CI, et al. Prophylactic value of pre-incision intra-aortic balloon pump: analysis of a statewide experience. J Thorac Cardiovasc Surg. 2000; 120: 1112–19.Find this resource:

36. Ranucci M, Castelvecchio S, Biondi A, de Vincentiis C, Ballotta A, Varrica A, Frigiola A, Menicanti L; for the Surgical and Clinical Outcome Research (SCORE) Group. A randomized controlled trial of preoperative intra-aortic balloon pump in coronary patients with poor left ventricular function undergoing coronary artery bypass surgery. Crit Care Med 2013; 41: 2476–83.Find this resource:

37. Croal BL, Hillis GS, Gibson PH, Fazal MT, El-Shafei H, Gibson G, Jeffrey RR, Buchan KG, West D, Cuthbertson BH Relationship between postoperative cardiac troponin I levels and outcome of cardiac surgery. Circulation (2006) 114: 1468–75Find this resource:

38. Chen JC, Kaul P, Levy JH, Haverich A, Menasche P, Smith PK, Carrier M, Verrier ED, Van de Werf F, Burge R, Finnegan P, Mark DB, Shernan SK Myocardial infarction following coronary artery bypass graft surgery increases healthcare resource utilization. Crit Care Med (2007) 35: 1296–1301Find this resource:

39. Muehlschlegel JD, Perry TE, Liu K, Nascimben L, Fox AA, Collard CD, Avery ED, Aranki SF, D’Ambra MN, Shernan SK, and Body SC for the CABG Genomics Investigators. Troponin is superior to electrocardiogram and creatinine kinase MB for predicting clinically significant myocardial injury after coronary artery bypass grafting. Eur. Heart J., July 2009; 30: 1574–83.Find this resource:

40. Mohammed AA, Agnihotri AK, van Kimmenade RRJ, Martinez-Rumayor A, Green SM, Quiroz R, Januzzi JL Prospective, comprehensive assessment of cardiac troponin T testing after coronary artery bypass graft surgery. Circulation 2009; 120: 843–50.Find this resource:

41. Thygesen K, Alpert JS, White HD, et al., the Writing Group on behalf of the Joint ESC/ACCF/AHA/WHF Task Force for the Universal Definition of Myocardial Infarction Third universal definition of myocardial infarction. Eur Heart J 2012; 33: 2551–67.Find this resource:

42. Ramsay J, Shernan S, Fitch J, Finnegan P, Todaro T, Filloon T, Nussmeier NA Increased creatine kinase MB level predicts postoperative mortality after cardiac surgery independent of new Q waves. J Thorac Cardiovasc Surg (2005) 129: 300–6Find this resource:

43. Ibanez B, James S, Agewall S, Antunes MJ, Bucciarelli-Ducci C, Bueno H, Caforio ALP, Crea F, Goudevenos JA, Halvorsen S, Hindricks G, Kastrati A, Lenzen MJ, Prescott E, Roffi M, Valgimigli M, Varenhorst C, Vranckx P, Widimský P. 2017 ESC Guidelines for the management of acute myocardial infarction in patients presenting with ST-segment elevation: The Task Force for the management of acute myocardial infarction in patients presenting with ST-segment elevation of the European Society of Cardiology (ESC). Eur Heart J. 2017 Aug 26. doi: 10.1093/eurheartj/ehx393.Find this resource:

44. Rubino AS, Onorati F, Santarpino G, Abdalla K, Caroleo S, Santangelo E, Renzulli A Early intra-aortic balloon pumping following perioperative myocardial injury improves hospital and mid-term prognosis. Interact Cardiovasc Thorac Surg 2009; 8: 310–15.Find this resource:

45. Davila-Roman VG, Waggoner AD, Hopkins WE, Barzilai B Right ventricular dysfunction in low output syndrome after cardiac operations: assessment by transesophageal echocardiography. Ann Thorac Surg 1995; 60: 1081–86.Find this resource:

46. Ballotta A, Ranucci M, Kunkl A, El Baghdady H, Bossone E, Castelvecchio S, Frigiola A, Menicanti L, Di Donato M, Mehta RH N-terminal pro-brain natriuretic peptide and outcomes in patients undergoing surgical ventricular restoration. Am J Cardiol 2010; 105: 640–4.Find this resource:

47. Canver CC, Chanda J Intraoperative and postoperative risk factors for respiratory failure after coronary bypass. Ann Thorac Surg 2003; 75, 853–57.Find this resource:

48. Zochios V, Klein AA, Jones N, et al. Effect of high flow nasal oxygen on pulmonary complications and outcomes after adult cardiothoracic surgery: a qualitative review. J Cardiothorac Vasc Anesth 2016; 30: 1379–85.Find this resource:

49. Bellomo R, Ronco C, Kellum JA, Mehta RL, Palevsky P, the ADQI workgroup: Acute renal failure-definition, outcome measures, animal models, fluid therapy and information technology needs the Second International Consensus Conference of the Acute Dialysis Quality Initiative (ADQI) Group. Crit Care 2004, 8: R204-12.Find this resource:

50. Ad-hoc working group of ERBP, Fliser D, Laville M, Covic A, Fouque D, Vanholder R, Juillard L, Van Biesen W. A European Renal Best Practice (ERBP) position statement on the Kidney Disease Improving Global Outcomes (KDIGO) clinical practice guidelines on acute kidney injury: part 1: definitions, conservative management and contrast-induced nephropathy. Nephrol Dial Transplant. 2012; 27: 4263–72.Find this resource:

51. Chertow GM, Lazarus JM, Christiansen CL, Cook EF, Hammermeister KE, Grover F, Daley J Preoperative renal risk stratification. Circulation 1997; 95: 878–84.Find this resource:

52. Mangano CM, Diamondstone LS, Ramsay JG, Aggarwal A, Herskowitz A, Mangano DT, for the Multicenter Study of Perioperative Ischemia Research Group. Renal dysfunction after myocardial revascularization: risk factors, adverse outcomes, and hospital resources utilization. Ann Intern Med 1998; 128: 194–203.Find this resource:

53. Ostermann ME, Taube D, Morgan CJ, Evans TW Acute renal failure following cardiopulmonary bypass: a changing picture. Intensive Care Med 2000; 26: 565–71.Find this resource:

54. Mehta RH, Grab JD, O’Brien SM, Bridges CR, Gammie JS, Haan CK, Ferguson B, Peterson ED and for the Society of Thoracic Surgeons National Cardiac Surgery Database Investigators. Bedside tool for predicting the risk of postoperative dialysis in patients undergoing cardiac surgery. Circulation 2006; 114: 2208–16.Find this resource:

55. Mangi AA, Christison-Lagay ER, Torchiana DF, Warshaw AL, Berger DL Gastrointestinal complications in patients undergoing heart operation. An analysis of 8709 consecutive cardiac surgical patients. Ann Surg 2005; 241: 895–904.Find this resource:

56. Abboud B, Daher R, Sleilaty G, Madi-Jebara S, El Asmar B, Achouch R, Jebara V Is prompt exploratory laparotomy the best attitude for mesenteric ischemia after cardiac surgery? Interact Cardiovasc Thorac Surg 2008; 7: 1079–83.Find this resource:

57. Ohri SK, Becket J, Brannan J, Keogh BE, Taylor KM Effects of cardiopulmonary bypass on gut blood flow, oxygen utilization, and intramucosal pH. Ann Thorac Surg 1994; 57: 1193–99.Find this resource:

58. Tao W, Zwischenberger JB, Nguyen TT, Vertrees RA, McDaniel LB, Nutt LK, Herndon DN, Kramer GC Gut mucosal ischemia during normothermic cardiopulmonary bypass results from blood flow redistribution and increased oxygen demand. J Thorac Cardiovasc Surg 1995; 110: 819–28.Find this resource:

59. Ranucci M, Ballotta A, Frigiola A, Boncilli A, Brozzi S, Costa E and Mehta RH Pre-operative homocysteine levels and morbidity and mortality following cardiac surgery. Eur Heart J 2009; 30: 995–1004.Find this resource:

60. Andersson B, Andersson R, Brandt J, Hoglund P, Algotsson L, Nilson J. Gastrointestinal complications after cardiac surgery - improved risk stratification using a new scoring model. Interact Cardiovasc Thorac Surg 2010; 10: 366–70.Find this resource:

61. Nilson J, Hansson E, Andresson B. Intestinal ischemia after cardiac surgery: analysis of a large registry. J Cardiothorac Surg 2013; 8: 156.Find this resource:

62. Kazui T, Yamasaki M, Abe K, Watanabe S, Kawazoe K. Non-obstructive mesenteric ischemia: a potentially lethal complication after cardiovascular surgery: report of two cases. Ann Thorac Cardiovasc Surg 2012; 18: 56–60.Find this resource:

63. Groesdonk HV, Klingele M, Schlempp S, Bomberg H, Schmied W, Minko P, Schafers HJ. Risk Factors for nonocclusive mesenteric ischemia after elective cardiac surgery. J Thorac Cardiovasc Surg 2013; 33: 210–17.Find this resource:

64. Klotz S, Vestring T, Rotker J, Schmidt C, Scheld HH, Schmid C. Diagnosis and treatment of nonocclusive mesenteric ischemia after open heart surgery. Ann Thorac Surg 2001; 72: 1583–6.Find this resource:

65. Klingele M, Bomberg H, Poppleton A, et al. Elevated procalcitonin in patients after cardiac surgery: a hint to non occlusive mesenteric ischemia. Ann Thorac Surg 2015; 99: 1306–13.Find this resource:

66. Kirolos AJ, Hjortnaes J, Kranenburg G, de Heer F, Kluin J. Mortality after cardiac surgery in patients with liver cirrhosis classified by Child-Pugh score. Interact Cardiovasc Thorac Surg 2015; 20: 520–30.Find this resource:

67. Despotis GJ, Avidan MS, Hogue CW Jr Mechanisms and attenuation of hemostatic activation during extracorporeal circulation. Ann Thorac Surg (2001) 72: S1821–831.Find this resource:

68. Murphy GJ, Reeves BC, Rogers CA, Rizvi SI, Culliford L, Angelini GD Increased mortality, postoperative morbidity, and cost after red blood cell transfusion in patients having cardiac surgery. Circulation 2007; 116: 2544–52.Find this resource:

69. Murphy GJ, Pike K, Rogers CA, et al. Liberal or restrictive transfusion after cardiac surgery. N Engl J Med 2015; 372: 997–1008.Find this resource:

70. Nakamura RE, Vincent JL, Fukushima JT, et al. A liberal strategy of red blood cell transfusion reduces cardiogenic shock in elderly patients undergoing cardiac surgery. J Thorac Cardiovasc Surg 2015; 150: 1314–20.Find this resource:

71. Ranucci M, Baryshnikova E, Castelvecchio S, Pelissero G; Surgical and Clinical Outcome Research (SCORE) Group. Major bleeding, transfusions, and anemia: the deadly triad of cardiac surgery. Ann Thorac Surg 2013; 96: 478–85.Find this resource:

72. Despotis GJ, Levine V, Saleem R, Spitznagel E, Joist JH Use of point-of-care test in identification of patients who can benefit from desmopressin during cardiac surgery: a randomised controlled trial. Lancet 1999; 354: 106–10.Find this resource:

73. Shore-Lesserson L, Manspeizer HE, DePerio M, Francis S, Vela-Cantos F, Ergin MA Thromboelastography-guided transfusion algorithm reduces transfusions in complex cardiac surgery. Anesth Analg 1999; 88: 312–19.Find this resource:

74. Ranucci M, Castelvecchio S, Romitti F, Isgrò G, Ballotta A, Conti D Living without aprotinin: the results of a 5-year blood saving program in cardiac surgery. Acta Anaesthesiol Scand 2009; 53: 573–80.Find this resource:

75. Fergusson DA, Hébert PC, Mazer CD, Fremes S, MacAdams C, Murkin JM, Teoh K, Duke PC, Arellano R, Blajchman MA, Bussières, JS, Côté D, Karski J, Martineau R, Robblee JA, Rodger M, Wells G, Clinch J, Pretorius R, for the BART Investigators. A comparison of aprotinin and lysine analogues in high-risk cardiac surgery. N Engl J Med 2008; 358: 2319–31.Find this resource:

76. Casati V, Guzzon D, Oppizzi M, Bellotti F, Franco A, Gerli C, Cossolini M, Torri G, Calori G, Benussi S, Alfieri O Tranexamic acid compared with high-dose aprotinin in primary elective heart operations: effects on perioperative bleeding and allogeneic transfusions. J Thorac Cardiovasc Surg 2000; 120: 520–27.Find this resource:

77. Casati V, Guzzon D, Oppizzi M, Cossolini M, Torri G, Calori G, Alfieri O Hemostatic effects of aprotinin, tranexamic acid and ε‎-aminocaproic acid in primary cardiac surgery. Ann Thorac Surg 1999; 68: 2252–57.Find this resource:

78. Despotis GJ, Levine V, Saleem R, Spitznagel E, Joist JH Use of point-of-care test in identification of patients who can benefit from desmopressin during cardiac surgery: a randomised controlled trial. Lancet 1999; 354: 106–10.Find this resource:

79. Mannucci PM, Levi M Prevention and treatment of major blood loss. N Engl J Med 2007; 356: 2301–11.Find this resource:

80. Ranucci M, Isgrò G, Soro G, Conti D, De Toffol B Efficacy and safety of recombinant activated factor VII in major surgical procedures: systematic review and meta-analysis of randomized clinical trials. Arch Surg 2008 143: 296–304.Find this resource:

81. Gill R, Herbertson M, Vuylsteke A, Olsen PS, von Heymann C, Mythen M, Sellke F, Booth F, Schmidt T. A Safety and efficacy of recombinant activated factor VII: a randomized placebo-controlled trial in the setting of bleeding after cardiac surgery. Circulation 2009; 120: 21–27.Find this resource:

82. Zaman AG, Archbold A, Helft G, Paul EA, Gurzen NP, Mills PG Atrial fibrillation after coronary artery bypass surgery: a model for preoperative risk stratification. Circulation. 2000; 101: 1403–8.Find this resource:

83. Halonen J, Hakala T, Auvinen T, et al. Intravenous administration of metoprolol is more effective than peroral administration in the prevention of atrial fibrillation after cardiac surgery. Circulation 2006; 114 (suppl): I1–4.Find this resource:

84. Maisel, WH, Rawn, JD, Stevenson, WG (2001) Atrial fibrillation after cardiac surgery. Ann Intern Med 135, 1061–1973Find this resource:

85. Almassi GH, Schowalter T, Nicolosi AC, et al. Atrial fibrillation after cardiac surgery: a major morbid event? Ann Surg 1997; 226: 501–13.Find this resource:

86. Villareal RP, Hariharan R, Liu BC, et al. Postoperative atrial fibrillation and mortality after coronary artery bypass surgery. J Am Coll Cardiol 2004; 43: 742–48Find this resource:

87. Amar D, Shi W, Hogue CW Jr, Zhang H, Passman RS, Thomas B, Bach PB, Damiano R, Thaler HT Clinical prediction rule for atrial fibrillation after coronary artery bypass grafting. J Am Coll Cardiol 2004; 44: 1248–53.Find this resource:

88. Daoud EG, Strickberger A, Man KC, et al. Preoperative amiodarone as prophylaxis against atrial fibrillation after heart surgery. N Engl J Med 1997; 337: 1785–91Find this resource:

89. Guarnieri T, Nolan S, Gottlieb SO, Dudek A, Lowry DR Intravenous amiodarone for the prevention of atrial fibrillation after open heart surgery: the Amiodarone Reduction in Coronary Heart (ARCH) trial. J Am Coll Cardiol 1999; 34: 343–47Find this resource:

90. Mahoney EM, Thompson TD, Veledar E, Williams J, Weintraub WC Cost-effectiveness of targeting patients undergoing cardiac surgery for therapy with intravenous amiodarone to prevent atrial fibrillation. J Am Coll Cardiol 2002; 40: 737–45.Find this resource:

91. Nayeem-Ul-Hassan, Dar AM, Wani ML, Rather HA, Ganie FA A comparative study on the effect of amiodarone and metaprolol for prevention of arrythmias after open heart surgery. Int Cardiovasc Res J 2013 7: 1–4.Find this resource:

92. Mariani J, Doval HC, Nul D, Varini S, Grancelli U, Ferrante D, Tognoni G, Macchia A N-3 Polyunsaturated fatty acids to prevent atrial fibrillation: updated systematic review and meta-analysis of randomized clinical trials. J Am Heart Assoc. 2013; 2: e 003055.Find this resource:

93. Shiga T, Wajima Z, Inoue T, Ogawa R Magnesium prophilaxis for arrhytmia after cardiac surgery: a meta-analysis of randomized controlled trials. Am J Med 2004; 117: 325–33.Find this resource:

94. Kowey PR, Dorian P, Mitchell LB, Pratt CM, Roy D, Schwartz PJ, Sadowski J, Sobczyk D, Bochenek A and Toft E Vernakalant Hydrochloride for the rapid conversion of atrial fibrillation after cardiac surgery: a randomized, double-blind, placebo-controlled trial. Circ Arrhythm Electrophysiol 2009; 2: 652–59.Find this resource:

95. Camm J, Lip GYH, De Caterina R, Savelieva I, Atar D, Hohnloser SH, Hindricks G, Kirchof P 2012 Focused update of the ESC guidelines for the management of atrial fibrillation. Europace 2012; 14: 1385–1413.Find this resource:

96. Zeriouh M, Sabashinov A, Choi YH, Fatullayev J, Reuter H, Popov AF, Langebartels G, Kimmig L, Rahmanian PB, Witter T, Neef K, Wippermann J, Wahlers T. A novel treatment strategy of new onset atrial fibrillation after cardiac surgery: an observational prospective study. J Cardiothorac Surg 2014; 9: 83–91.Find this resource:

97. Gillinov AM, Bagiella E, Moskowitz AJ, et al. Rate control versus rhytm control for atrial fibrillation after cardiac surgery. N Engl J Med 2016; 344: 1911–21.Find this resource:

98. Crystal E, Connolly SJ, Sleik K, Ginger TJ, Yusuf S Interventions on prevention of postoperative atrial fibrillation in patients undergoing heart surgery: a meta-analysis. Circulation. 2002; 106: 75–80.Find this resource:

99. Fuster V, Rydén LE, Cannom DS, Crijns HJ, Curtis AB, Ellenbogen KA, Halperin JL, Le Heuzey JY, Kay GN Lowe JE, Olsson SB, Prystowsky EN, Tamargo JL, Wann S, Smith SC Jr, Jacobs AK, Adams CD, Anderson JL, Antman EM, Halperin JL, Hunt SA, Nishimura R, Ornato JP, Page RL, Riegel B, Priori SG, Blanc JJ, Budaj A, Camm AJ, Dean V, Deckers JW, Despres C, Dickstein K, Lekakis J, McGregor K, Metra M, Morais J, Osterspey A, Tamargo JL, Zamorano JL; American College of Cardiology/American Heart Association Task Force on Practice Guidelines; European Society of Cardiology Committee for Practice Guidelines; European Heart Rhythm Association; Heart Rhythm Society. ACC/AHA/ESC 2006 Guidelines for the Management of Patients with Atrial Fibrillation: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and the European Society of Cardiology Committee for Practice Guidelines (Writing Committee to Revise the 2001 Guidelines for the Management of Patients with Atrial Fibrillation): developed in collaboration with the European Heart Rhythm Association and the Heart Rhythm Society. Circulation 2006; 114: e257-354Find this resource:

100. Budera P, Straka Z, Osmancik P, Vanek T, Jelinek S, Hvalicka J, Fojt R, Cervinka P, Hulman M, Smid M, Maly M, Widimsky P Comparison of cardiac surgery with left atrial ablation vs. Cardiac surgery without atrial ablation in patients with coronary and/or valvular heart disease plus atrial fibrillation: final results of the PRAGUE-12 multicenter randomized study. European Heart Journal 2012; 33: 2644–52.Find this resource:

101. Meurin P, Weber H, Renaud N, Larrazet F, Tablet JY, Demolis P, et al. Evolution of the post-operative pericardial effusion after day 15: the problem of the late tamponade. Chest 2004; 125: 2182–7.Find this resource:

102. Vranckx P, Potpara T, Dagres N, et al. Non vitamin K oral anticoagulants in patients with atrial fibrillation after cardiac surgery: the results of the Europena Heart Rhytm association survey: Europace 2016; 18: 1113–6.Find this resource:

103. Sigurdsson MI, Longford NT, Heayarpour M, et al. Duration of postoperative atrial fibrillation after cardiac surgery is associated with worsened long term survival. Ann Thor Surg 2016; 102: 2018–26.Find this resource:

104. Liu X, Zhang K, Xie G, et al. Dexmdetomidine sedation reduces atrial fibrillation after cardiac surgery compared to propofol. Critical Care 2016; 20: 298.Find this resource:

105. Ad N, Holmes SD, Shuman DJ, Pritchard G, Miller CE. Amiodarone after surgical ablation for atrial fibrillation: is it really necessary? A prospective randomized controlled trial. J Thorac Cardiovasc Surg 2015; pii: S0022-5223(15)01251-9.Find this resource:

106. Selim M Perioperative stroke. N Engl J Med 2007; 356: 706–13.Find this resource:

107. Stamou SC, Hill PC, Dangas G, Pfister AJ, Boyce SW, Dullum MK, Bafi AS, Corso PJ Stroke after coronary bypass. Incidence, predictors and clinical outcome. Stroke 2001; 32: 1508–13.Find this resource:

108. Bucerius J, Gummert JF, Borger MA, Walther T, Doll N, Onnasch JF, Metz S, Falk V, Mohr FW Stroke after cardiac surgery: a risk factor analysis of 16184 consecutive adult patients. Ann Thorac Surg 2003; 75: 472–78Find this resource:

109. Katz ES, Tunick PA, Rusinek H, Ribakove G, Spencer PC, Kronzon I Protruding aortic atheromas predict stroke in elderly patients undergoing cardiopulmonary bypass: experience with intraoperative transesophageal echocardiography. J Am Coll Cardiol 1992; 20: 70–77.Find this resource:

110. Wareing TH, Davila-Roman VG, Barzilai B, Murphy SF, Kouchoukos NT Management of the severely atherosclerotic ascending aorta during cardiac operations. A strategy for detection and treatment. J Thorac Cardiovasc Surg 1992; 103; 453–62.Find this resource:

111. Biancari F, Mikkola R, Heikinen J, Lahtinen J, Airasksinen KEJ, and Juvonen T Estimating the risk of complication related to reexploration for bleeding after cardiac surgery: a systematic review and meta-analysis. European Journal of Cardio-Thoracic Surgery 2012; 41: 50–55.Find this resource:

112. Mikkola R, Gunn J, Heikkinen J, Wistbacka JO, Teittinen K, Kuttila K, Lahtinen J, Juvonen T, Airaksinen JKE, Biancari F Use of blood products and risk of stroke after coronary bypass surgery. Blood Transf 2012; 10: 490–501Find this resource:

113. Endo D, Kato TS, Iwamura T, Oishi A, Yokoyama Y, Kuwaki K, Inaba H, Amano A. The impact of surgical left atrial appendage amputation/ligation on stroke prevention in patients undergoing off-pump coronary artery bypass grafting. Heart Vessels. 2017;32:726–734Find this resource:

114. Newman MF, Kirchner JL, Phillips-Bute B, et al. Longitudinal assessment of neurocognitive function after coronary-artery bypass surgery. N Engl Med 2001; 344: 395–402.Find this resource:

115. Gosselt ANC, Slooter AJC, Boere PRQ, Zaal IJ. Risk factors for delirium after cardiac surgery. Crit Care 2015; 19: 346.Find this resource:

116. Rudolph JL, Babiniak VL, Birjiniuk V, et al. Atherosclerosis is associated with delirium after coronary artery by-pass surgery. J Am Geriatr Soc 2005; 53: 462–6.Find this resource:

117. Park JB, Bang SB, Chee HK, Kim JS, Lee SA, Shin JK. Efficacy and Safety of Dexmedetomidine for Postoperative Delirium in Adult Cardiac Surgery on Cardiopulmonary Bypass. Korean J Thorac Cardiovasc Surg 2014; 47: 249–54.Find this resource:

118. Djaiani G, Silverton N, Fedorko L, et al. Dexmedetomidine versus propofol sedation reduces delirium after cardiac surgery. Anesthesiology 2016; 124: 362–8.Find this resource:

119. Kamiya H, Tanzeem N, Akhyari P, Pedraza A, Kallenbach K, Lichtenberg A and Karck M Impact of severe postoperative complications after cardiac surgery on mortality in patients aged over 80 years. Annals of Vascular Disease; advance published date July 31, 2013.Find this resource: