Postoperative pulmonary dysfunction is a multifactorial complication in patients undergoing cardiac surgery with cardiopulmonary bypass (CPB). Numerous risk factors including individual, surgery- and anesthesia-related have been identified. Exacerbated systemic and pulmonary inflammatory response to CPB is one of the most studied mechanisms of lung injury in this patient setting. However, current literature lacks specific intraoperative mechanical ventilation (MV) strategies associated with a significant improvement in patients’ outcomes. We reviewed the randomized clinical trials and other reports published within the last 5 years involving patients undergoing cardiac surgery with CPB in order to summarize the existing MV strategies used in these patients and their associated outcomes. Moreover, we described the pathophysiological mechanisms involved in post- CPB lung injury and the mechanistic effects of protective ventilation.
Impaired postoperative pulmonary function is a common and multifactorial complication after cardiac surgery[
Mild respiratory dysfunction is commonly reported after cardiac surgery under CPB with a small percentage of patients developing severe lung dysfunction[
A comprehensive review of current literature was carried out aiming to describe the pulmonary physio-pathological changes experienced by patients undergoing cardiac surgery with and without CPB and treated under different ventilation strategies. Likewise, the incidence of PPCs in patients with and without continuous MV during CPB was analyzed.
A literature search on PubMed, Embase, and Cochrane Library databases was carried out in order to identify manuscripts published between 01 Jan 2014 and 31 Jan 2019 describing MV and pulmonary complications in patients undergoing CPB surgery. We used Medical Subject Headings involving the terms “MV” (combined with “CPB”, “CPB and lung injury”, “CPB and morbidity”, “CPB and mortality”, “CPB and pulmonary perfusion”, “cardiac surgery and oxygen diffusion”), “CPB” [combined with “pulmonary complications”, “CPAP”, “positive end-expiratory pressure (PEEP)”, “lung injury”, “lung mechanics”], and “lung protective ventilation in CPB surgery”. Our search was limited to manuscripts in English language, involving adult patients only, clinical trials (including phase I-IV studies), narrative reviews, and systematic reviews (with or without meta-analysis). Case reports were only considered if they were needed to support specific clinical findings not previously discussed. Moreover, we excluded manuscripts referring to CPB surgery outside the scope of this review, conference abstracts, thesis, and trials involving children or patients undergoing other cardiac surgeries different from CPB.
Initially, we identified 207 manuscripts out of which 46 were duplicates. After title/abstract screening, 113 manuscripts were out of the scope of this review and thereby excluded. Therefore, 48 articles qualified for full-test revision. Thirty-five (
Flow diagram
A total of 3 RCTs and 1 prospective observational trial (
Summary of the manuscripts included in our review
Authors | Year | Research Method | Sample Size | Main outcome | Comments |
---|---|---|---|---|---|
Bechtel |
2014 | Review | NA | Describe current literature about anesthetic management in patients undergoing CPB | Protecting ventilation techniques during CPB may be associated with decreased inflammatory response. However, no significant overall improvement in respiratory and oxygenation parameters has been reported |
Beer |
2014 | RCT | 30 | Chemokines serum levels | CCL4 serum levels from POD1 to POD5 were significantly reduced in the ventilated patients when compared to the non-ventilated group ( |
Young[ |
2014 | Review | NA | To describe current strategies to reduce the postoperative inflammatory lung injury in patients undergoing CPB | Increased resistance in the pulmonary circuit may result from no ventilation during CPB. Further RCTs are required to elucidate the impact of mechanical ventilation during CPB on postoperative pulmonary outcomes |
Beer |
2015 | RCT | 30 | Matrix metalloproteinases levels | Matrix metalloproteinases levels were significantly reduced at different time-points in patients who underwent mechanical ventilation during CPB. However, clinical implications should be addressed in future trials |
Ferrando |
2015 | Review | NA | Review pulmonary protective strategies during CPB | CPAP, recruitment maneuvers, and low VT during CPB have been associated with better postoperative lung mechanics. In addition, maintaining certain level of pulmonary perfusion during CPB may positively impact these outcomes |
Gaudriot |
2015 | Prospective Observational | 50 | Impact of Mechanical ventilation during CPB on postoperative immune response | Pro-inflammatory TNF-α and immunosuppressive IL-10 were significantly reduced in patients who received mechanical ventilation during CPB ( |
Huffmyer |
2015 | Review | NA | Pulmonary complications after CPB: etiology, risk factors, and prophylaxis | Intermittent ventilation, low VT and recruitment maneuvers have been associated with reduced atelectasis and improved lung mechanics. Mixed results have been reported in terms of inflammatory markers and clinical outcomes. |
Lellouche |
2015 | Review | NA | Mechanical ventilation strategies In patients undergoing cardiac surgery | Protective ventilation strategies are associated with improved lung mechanics, decreased pro-inflammatory cytokines, and reduced postoperative intubation time and ICU LOS |
Bignami |
2016 | Review | NA | Postoperative lung dysfunction and mechanical ventilation strategies to prevent it in patients undergoing CPB | No ventilation during CPB has been linked to increased lysosomal enzymes in lungs circulation and increased incidence of ARDS. Low VT 6-8 mL/Kg of IBW, PEEP, recruitment maneuvers, and FiO2 < 80% have been associated with decreased morbidity, hospital LOS, and PPCs. Ventilation before and after the CPB may significantly affect lung mechanics as well. Mixed results have been reported in terms of CPAP use during CPB and its association with improved postoperative pulmonary outcomes. Only one trial has reported high-frequency ventilation during CPB with no significant respiratory improvements reported |
Chi |
2017 | Meta-analysis | NA | Impact of mechanical ventilation during CPB on PPCs when compared to non-ventilated patients | Mechanical ventilation during CPB results in an improved oxygenation and gas exchanged. However, comparable incidences of PPCs and hospital LOS have been reported among groups |
Toikkanen |
2017 | RCT | 47 | Mechanical ventilation and its effect on cytokines levels after CABG | CABG with CPB is associated with an increased pro-inflammatory cytokines pulmonary passage when compared to patients where CPB was not used. Moreover, lung ventilation did not change cytokines concentration in patients undergoing CABG with CPB. Main limitation: sample size, patient selection (e.g., lung disease was excluded), and no subgroups (ventilation vs. non-ventilation) in patients undergoing CABG without CPB |
Bignami |
2018 | Review | NA | Describe current status of protective ventilation strategies and their impact on postoperative outcomes | In patients undergoing cardiothoracic surgery, protective ventilation strategies are associated with a decreased inflammatory response and should be considered in patients at high risk of PPCs. CPAP, low VT, and non-ventilated lungs are among the options for mechanical ventilation during CPB |
Wang |
2018 | Systematic Review and Meta-analysis | NA | Different strategies used for mechanical ventilation during CPB and postoperative outcomes | CPAP between 5-15 cm H2O during CPB may be associated with short-term benefits such as improved gas exchange and oxygenation. However, no significant differences in these variables were found when comparing patients undergoing mechanical ventilation during CPB and those non-ventilated |
CPB: cardiopulmonary bypass; RCT: randomized clinical trial; CCL: chemokine ligand; POD: postoperative day; CPAP: continuous positive airway pressure; VT: tidal volume; TNF-α: tumor necrosis factor alpha; IL: interleukin; ICU: intensive care unit; LOS: length of stay; IBW: ideal body weight; PEEP: positive end-expiratory pressure; FiO2: inspired fraction of oxygen; PPCs: postoperative pulmonary complications; CABG: coronary artery bypass graft; ARDS: acute respiratory distress syndrome
Perioperative clinical outcomes (e.g., atrial fibrillation, perioperative myocardial infarction, and pericardial tamponade) and 28-day mortality after cardiac surgery were assessed in 2 of the RCTs included in this review[
A recent systematic review and meta-analysis described the impact of different MV strategies during CPB on postoperative outcomes in adult patients undergoing cardiac surgery. A total of 15 RCTs were included in this analysis, 13 trials in patients undergoing coronary artery bypass grafting (CABG) and 2 trials in patients undergoing valve surgery. Subsequently, only 5 studies (134 patients in total) reported the use of CPAP during CPB and its impact on oxygenation. Other primary end-points were PaO2/FiO2 ratio (5 studies), the alveolar-arterial O2 gradient or P(A-a)O2 (9 studies), hospital LOS (6 studies), and the duration of postoperative MV (6 studies)[
Seven review manuscripts have summarized some of the current findings in terms of MV strategies and perioperative lung mechanics in patients undergoing cardiac surgery.
Postoperative respiratory dysfunction is the most common postoperative complication in patients undergoing cardiac surgery under CPB affecting 10% to 25% of these patients and also associated with high mortality rates[
Chronic obstructive pulmonary disease, low ventricular ejection fraction (EF) (i.e., EF < 30%), hypertension, blood transfusions, emergency surgery, previous cardiac surgery, combined procedures (i.e., cardiac and aortic procedures), active endocarditis, age > 70 are some of the patient-related risk factors associated with respiratory insufficiency after cardiac surgery[
Several reports identified a strong association between general anesthesia and impaired postoperative pulmonary function. Prolonged time in supine position and muscle relaxation have been linked to a significant reduction in both, functional residual capacity (FRC) and lung volume, resulting from a cephalic displacement of the diaphragm and the loss of balance between the elastic recoil of the lung and the outward forces of the chest wall. This reduction in FRC promotes alveolar collapse (i.e., atelectasis) and increases airway resistance with subsequent increased resistance to thoracic blood flow circulation. Furthermore, the volatile agents inhibit pulmonary hypoxic vasoconstriction whereas intravenous agents may decrease the hypoxic and hypercapnic ventilatory response. Intubation along with the aforementioned mechanisms may result in ventilation-perfusion mismatch, abnormal shunt fraction, and wider AaDO2[
Numerous reports describe the association between the surgical technique and changes in respiratory mechanics and lung function[
In addition to direct nerve injury (i.e., neuropraxia), the LIMA retractor has been also associated with lesion of the left internal oblique abdominal, external oblique abdominal and rectus abdominis muscles[
Blood transfusion is used in 30%-60% of patients undergoing cardiac surgery and the reported incidence of transfusion-related acute lung injury (TRALI) is 2.5%[
Tissue plasminogen activating factor, pro-inflammatory mediators (i.e., cytokines, activated leukocytes, lipids), pro-coagulants, and platelet factors are present in the cardiotomy suction blood. Numerous reports have shown the detrimental effects associated with these mediators during re-transfusion of unwashed blood collected in the pericardium including an increased inflammatory response with impaired lung function and hemostasis[
In spite of innovations in biocompatibility of CPB circuit’s surfaces, the inflammatory response associated to extracorporeal circulation with subsequent anti-inflammatory response as well as the ischemia-reperfusion injury, continue to have a significant impact on postoperative morbidity and mortality after cardiac surgery[
Type II alveolar cell dysfunction, inactivation of large aggregate by alveolar edema fluid, and/or large aggregate leakage across the damaged alveolar capillary membrane are some of the effects of apnea and lung collapse to FRC during CPB, being the inflammatory response triggered by the use of a foreign bypass circuit during extracorporeal circulation[
Under physiologic conditions, bronchial circulation represents 3%-4% of the pulmonary blood flow and may decrease during CPB[
Increased oxygen concentrations are commonly administered during CPB in order to avoid cellular hypoxia, reduce gaseous micro-embolism, and improve neutrophils’ functionality[
Different strategies such as CPAP with and without PEEP have been implemented during MV under CPB. Current evidence about the use of MV as a mechanistic strategy for lung protection during CPB remains controversial. Early studies examined the effects of CPAP during CPB without showing any significant beneficial effects on oxygenation[
Even though only a small amount of patients undergoing cardiac surgery may develop acute respiratory distress syndrome (ARDS), the reported mortality rates may reach up to 50%[
John and Ervine[
Gagnon
Discontinuation of the pulmonary artery circulation during CPB significantly affects the bronchial blood flow and metabolic demand which results in ischemia-reperfusion injury. Nevertheless, maintaining pulmonary circulation and ventilation during CPB have been associated with reduced ischemia-reperfusion damage in preclinical models[
In humans, the impact of continuous pulmonary perfusion during extracorporeal circulation on reducing postoperative lung injury remains controversial[
A variety of MV strategies may have potential benefits in patients undergoing cardiac surgery with CPB. PMV is a useful mechanistic strategy during CPB associated with reduced systemic and inflammatory responses and thereby, lung injury. Nevertheless, the impact of these findings on postoperative morbidity and mortality has not been clearly established. Future prospective RCTs should address the need for clinical data describing both, short- and long-term outcomes in patients undergoing cardiac surgeries with CPB under MV.
Made substantial contributions to conception and outline of this manuscript: Echeverria-Villalobos M
Made substantial contributions to data search, interpretation, and writing: Echeverria-Villalobos M, Munlemvo DM, Fiorda-Diaz J, Essandoh MK
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All authors declared that there are no conflicts of interest.
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© The Author(s) 2019.