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Lung Injury and Acute Respiratory Distress Syndrome After Cardiac Surgery
Lung Injury and Acute Respiratory Distress Syndrome After Cardiac Surgery R. Scott Stephens, MD, Ashish S. Shah, MD, and Glenn J. R. Whitman, MD Division of Pulmonary and Critical Care Medicine, Department of Medicine, and Division of Cardiac Surgery, Department of Surgery, The Johns Hopkins University, Baltimore, Maryland
As many as 20% of patients undergoing cardiac surgery will have acute respiratory distress syndrome during the perioperative period, with a mortality as high as 80%. If patients at risk can be identified, preventative measures can be taken and may improve outcomes. Care for patients with acute respiratory distress syndrome is supportive, with low tidal volume ventilation being the mainstay of therapy. Careful fluid management, minimi-
zation of blood product transfusion, appropriate nutrition, and early physical rehabilitation may improve outcomes. In cases of refractory hypoxemia, rescue therapies such as recruitment maneuvers, high-frequency oscillatory ventilation, and extracorporeal membrane oxygenation may preserve life. (Ann Thorac Surg 2013;95:1122–9) © 2013 by The Society of Thoracic Surgeons
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Risk Factors and Specific Etiologies
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he acute respiratory distress syndrome (ARDS) is a devastating syndrome of acute hypoxemic respiratory failure and bilateral pulmonary infiltrates [1–3]. The recently published 2012 Berlin Definition of ARDS [3] describes ARDS as hypoxemia, occurring within 1 week of a known clinical insult or new or worsening respiratory symptoms, associated with bilateral opacities on chest imaging not fully explained by pleural effusions, atelectasis, or nodules, and not fully explained by cardiac failure or fluid overload. Formerly described as a subset of acute lung injury (ALI), with ALI describing patients with a ratio of PaO2 to fraction of inspired oxygen (FiO2) equal to or less than 300, and ARDS reserved for patients with PaO2:FiO2 equal to or less than 200, ARDS is now divided into three categories: mild ARDS (200 mm Hg ⬍ PaO2:FiO2 ⱕ300 mm Hg with PEEP [positive endexpiratory pressure] or continuous positive airway pressure ⱖ5 cm H2O); moderate ARDS (100 mm Hg ⬍ PaO2:FiO2 ⱕ200 mm Hg with PEEP ⱖ5 cm H2O); and severe ARDS (PaO2:FiO2 ⱕ100 mm Hg with PEEP ⱖ5 cm H2O). Cardiac surgery is a known risk factor for ARDS; of the more than 300,000 patients who undergo cardiac surgery every year in the United States, as many as 20% will have ARDS [4 –9]. The mortality associated with ARDS approaches 40% in the general population, but among post– cardiac surgery patients, mortality may be as high as 80% [10, 11]. Survivors may have increased intensive care unit (ICU) and hospital length of stay, as well as substantial long-term physical and psychological morbidity [12]. An understanding of ARDS risk factors and the principles of its management may help both to prevent ARDS after cardiac surgery and to improve patient outcomes after ARDS has occurred. Address correspondence to Dr Stephens, Division of Pulmonary and Critical Care Medicine, 5501 Hopkins Bayview Circle, 4th Flr, Asthma and Allergy Center, Baltimore, MD 21224; e-mail: [email protected].
© 2013 by The Society of Thoracic Surgeons Published by Elsevier Inc
Many of the techniques and sequelae of cardiac surgery increase the risk of ARDS. Cardiopulmonary bypass (CPB), which induces a systemic inflammatory state, and pulmonary ischemia-reperfusion (IR) injury have both been associated with ARDS. The use of allogenic blood products exposes patients to the risk of transfusionrelated acute lung injury (TRALI). Pharmaceuticals such as amiodarone have the capacity to induce drug-related ALI. Finally, all patients undergoing cardiac surgery are intubated, sedated, and mechanically ventilated, exposing them to the risks of aspiration, ventilator-associated pneumonia, and ventilator-induced lung injury.
Surgical Procedure Performed Type of surgery greatly influences the risk of developing ARDS. Among all patients undergoing cardiac surgery, the risk of ARDS may be as high as 10%, but that risk is increased to nearly 17% among patients undergoing aortic surgery [8]. Longer bypass times, the use of hypothermic circulatory arrest, and requirement for more blood products may all play roles in increasing risk. Emergent repair of aortic catastrophe carries an even higher risk of respiratory failure—nearly 50% (13). High rates of respiratory failure (more than 20%) have also been reported after left ventricular assist device placement [14], although not all of these failures may be due to ARDS. Postoperative respiratory failure is associated with higher 1-year mortality among ventricular assist device recipients [14].
Cardiopulmonary Bypass Although the development of CPB made open heart surgery possible, saving hundreds of thousands of lives, the circulation of blood through an artificial extracorporeal circuit can incite systemic and pulmonary injury. During CPB, bronchial artery flow is maintained, but 0003-4975/$36.00 http://dx.doi.org/10.1016/j.athoracsur.2012.10.024
Abbreviations and Acronyms ALI ⫽ acute lung injury ARDS ⫽ acute respiratory distress syndrome CPB ⫽ cardiopulmonary bypass ECMO ⫽ extracorporeal membrane oxygenation FiO2 ⫽ fraction of inspired oxygen ICU ⫽ intensive care unit IR ⫽ ischemia-reperfusion PBW ⫽ predicted body weight PEEP ⫽ positive end-expiratory pressure PGD ⫽ primary graft dysfunction TRALI ⫽ transfusion-related acute lung injury VAP ⫽ ventilator-associated pneumonia VT ⫽ tidal volume
pulmonary arterial flow is markedly decreased. Concurrently, ventilation of the lungs is typically stopped to improve surgical exposure and field stability. The absence of ventilation in combination with reduced blood flow to the lungs may increase susceptibility to pulmonary injury. Cardiopulmonary bypass also initiates a profound systemic inflammatory cascade that can lead to pulmonary injury. As many as 60% of patients have increased pulmonary vascular permeability during CPB [15]. Polymorphisms in the interleukin-6 and interleukin-18 genes may predispose toward ALI after CPB [16, 17]. Ameliorating the injurious effects of CPB is an area of active investigation [18].
Ischemia-Reperfusion Transient ischemia and subsequent reperfusion of the lungs can result in the production of injurious reactive oxygen species [19, 20]. Some degree of pulmonary IR injury predictably occurs during and after CPB and during resuscitation from shock. Longer periods of pulmonary ischemia and subsequent IR injury occur during procedures such as pulmonary endarterectomy, hypothermic circulatory arrest, and lung transplantation. Extrapulmonary IR can also contribute to lung injury: in aortic procedures, hepatosplanchnic IR releases inflammatory mediators that contribute to the increase in pulmonary vascular permeability [21].
Pulmonary Endarterectomy Pulmonary endarterectomy for chronic thromboembolic pulmonary hypertension can dramatically improve functional status. However, these patients are uniquely susceptible to reperfusion-induced high-permeability pulmonary edema, resulting in profound shunt physiology and severe hypoxemia. Limited to portions of the lung from which proximal vascular obstruction has been removed, this generally occurs in the first 72 hours postoperatively. The management of patients after pulmonary endarterectomy has recently been reviewed [22].
Lung Transplantation Of the approximately 2,700 patients in the United States who undergo lung transplantation each year [23], 10% to
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25% will experience primary graft dysfunction (PGD). Primary graft dysfunction is a form of ARDS that occurs in the first 72 hours after lung transplantation and confers a significant increase in mortality [24]. Primary graft dysfunction is multifactorial in etiology; IR injury to the pulmonary endothelium and physiologic changes associated with donor brain death are thought to be of primary importance [24]. Obesity is a risk factor for PGD, as is the use of CPB, ventilator-induced lung injury, and large volume transfusion of blood products [24, 25]. Importantly, although PGD typically improves within 3 to 5 days if the patient survives, the occurrence of PGD increases the risk of bronchiolitis obliterans syndrome and allograft failure [26]. Prevention of this entity is essential to the long-term survival of lung transplant recipients.
Transfusion-Related Acute Lung Injury Cardiac surgical patients frequently require blood product support for anemia, thrombocytopenia, or coagulopathy. All transfusions carry the risk of TRALI, the leading cause of transfusion-related morbidity and mortality. Transfusion-related acute lung injury has been linked to longer ventilator times and increased ICU length of stay [27, 28]. Defined as the acute onset of hypoxia and bilateral pulmonary infiltrates within 6 hours of a transfusion, TRALI can present with tachypnea, cyanosis, dyspnea, and fever [29]. Mortality ranges from 5% to 25%. Cardiac surgery has been identified as an independent risk factor for TRALI [28]. The incidence of TRALI has been reported to be 2.5% among cardiac surgical patients [27]; that is probably an underestimate [30]. TRALI is likely immunemediated, as donor-related antileukocyte antibodies or antibody-producing donor leukocytes trigger neutrophil activation with resultant pulmonary endothelial damage and high-permeability edema [27, 31]. Transfusion of plasma-rich products such as fresh frozen plasma and platelets, especially from multiparous female donors, carries a higher risk of TRALI [27, 30, 32]. Transfusion of red cells is not harmless, and increases pulmonary permeability in a dose-dependent fashion [33, 34]. In addition, TRALI may be more likely in the presence of other ALI risk factors (30). Transfusion can also lead to transfusion-associated circulatory overload, which also develops acutely but responds rapidly to diuresis [29]. Transfusion-associated circulatory overload and TRALI can coexist, leading to mixed hydrostatic and permeability edema. Even in the absence of TRALI or transfusion-associated circulatory overload, transfusion increases pulmonary complications after cardiac surgery [35]. A restrictive transfusion strategy, targeting a hemoglobin of 7 to 8 mg/dL rather than 10 to 12 mg/dL, may help avoid the complications of transfusions. Although the incidence of lung injury was not a specific endpoint, the safety of a restrictive transfusion strategy after cardiac surgery was shown in a 500-patient randomized controlled trial [36].
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Table 1. Modifiable Acute Respiratory Distress Syndrome Risk Factors and Preventative Measures Risk Factor Cardiopulmonary bypass Aortic surgery Ventricular assist device insertion Transfusion of blood products Ventilator-associated lung injury Ventilator-associated pneumonia
Preventative Measure None None None Minimize blood product administration Low-tidal volume ventilation, early extubation Head of bed at 30 degrees or more, chlorhexidine mouth cleansing, sedation vacations, subglottic drainage of secretions, early extubation
Drug Toxicity
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Many pharmaceuticals have been reported to induce acute lung injury. In cardiac surgical patients, amiodarone, routinely used for prophylaxis and treatment of arrhythmias, is a potential cause of drug-induced lung injury. Amiodarone has well-described pulmonary toxicity, which can present as fulminant ARDS after only brief treatment courses (5 to 10 days) [37] or as subacute respiratory failure. If this entity is suspected, amiodarone should be stopped immediately. Steroids may be of some use [38]. Amiodarone has also been associated with increased mortality among lung and heart-lung transplant patients, and should be used with caution in these populations [39]. Amiodarone lung toxicity has been comprehensively reviewed [38] (www.pneumotox.com is an excellent resource on medication-associated lung injury).
Prevention and Management Identification of Patients at Risk The identification of patients at high risk for ARDS is an area of active investigation. If at-risk patients can be identified, targeted preventative measures may decrease the likelihood of ARDS developing (Table 1). Such measures could include avoiding unnecessary transfusions, appropriate mechanical ventilator settings, and early extubation, before ventilator-induced lung injury and ventilator-associated pneumonia (VAP) can occur. All cardiac surgical patients are at risk for ARDS, with patients undergoing aortic surgery, lung transplantation, and emergent procedures at even higher risk [8]. Gajic and associates [8] recently proposed a lung injury prediction score, which includes such factors as the presence of shock, sepsis, high-risk surgery, obesity, hypoalbuminemia, administration of high levels of FiO2, acidosis, and diabetes mellitus, all relevant to cardiac surgical patients. Smartphone-based applications can predict prolonged postoperative ventilatory times (eg, CV Surgery Ventilator Risk, Edward Bender, MD).
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General Care Fundamental critical care principals are vital to the care of all post– cardiac surgery patients. As sepsis is a cause of ARDS, efforts to prevent ICU-acquired infections are mandatory. To prevent central line associated bloodstream infections, central venous catheters should be inserted sterilely with full barrier precautions, and removed as soon as no longer needed [40]. Urinary catheters should be removed as soon as feasible [41]. Ventilator-associated pneumonia is a risk factor for ARDS and increases mortality when it develops in patients with preexisting ARDS [42]. The use of “ventilator bundles” consisting of measures such as semirecumbent (head of bed at 30 degrees or higher) positioning, mouth cleansing with chlorhexidine, and minimizing sedation have been shown to decrease the incidence of ventilator-associated pneumonias [43, 44]. Endotracheal tubes that permit intermittent drainage of subglottic secretions may also decrease the rate of VAP [45].
Mechanical Ventilator Strategies The cornerstone of ALI/ARDS management is lungprotective mechanical ventilation with low tidal volumes. A landmark ARDS Network study compared ventilation with tidal volumes of 6 mL/kg predicted body weight (PBW) to tidal volumes (VT) of 12 mL/kg PBW in patients with ARDS. A volume-assist control mode was used, and tidal volumes were adjusted to keep the end-inspiratory plateau pressure less than 30 cm H2O and 50 cm H2O, respectively. The PEEP and FiO2 were set according to a predetermined protocol. Mortality was 31% in the low VT group versus 39.8% in the traditional VT group [46]. Protective ventilation can also be achieved with pressure control modes, with the inspiratory pressure kept below 30 cm H2O and adjusted to target a VT of 6 mL/kg PBW. Tidal volumes should be set to PBW, which is determined by sex and height, not actual body weight (Table 2). We recommend that PEEP and FiO2 be set according to the ARDS Network scale. Patients with diffuse symmetric infiltrates may have a more robust oxygenation response to PEEP than patients with unilateral or focal infiltrates. Conversely, higher PEEP can decrease cardiac output, cause pulmonary overdistention, increase pulmonary vascular resistance, and increase dead space [47]. Application of PEEP, therefore, requires a judicious approach and close monitoring. In general, oxygen and PEEP should be titrated to maintain a PaO2 greater than 55 to 60 mm Hg, or SpO2 greater than 88%, although some clinical scenarios (eg, neurologic injury) mandate a higher oxygenation goal. Use of low tidal volumes may require increases in respiratory rate to maintain adequate ventilation; in general a mild-to-moderate respiraTable 2. Equations to Calculate Predicted Body Weight Males 50 ⫹ 0.91 (height in centimeters ⫺ 152.4)
Females 45.5 ⫹ 0.91 (height in centimeters ⫺ 152.4)
Published by the ARDS Network [46].
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Fluid Management Cardiac surgical patients routinely become significantly volume overloaded as a consequence of cardiopulmonary bypass and intraoperative and postoperative fluid resuscitation. Increased intravascular hydrostatic pressure can worsen the capillary leak of acute lung injury. In a trial of conservative or liberal fluid management in ARDS patients [57], patients randomly assigned to the conservative strategy had a cumulative fluid balance of ⫺136 ⫾ 491 mL over 7 days, compared with a balance of ⫹6992 ⫾ 502 mL in patients in the liberal strategy group.
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The conservative group had improved lung injury scores and oxygenation indices, lower plateau pressures, required less PEEP, and had more ventilator-free days and more ICU-free days. As patients with ARDS often have acute kidney injury, clinicians often need to decide whether to administer diuretic therapy. A study of patients with ARDS and acute kidney injury found that a positive fluid balance was associated with an increased risk of mortality, and that diuretic therapy after acute kidney injury improved mortality among patients with ARDS [58]. Based on these studies, we recommend minimizing fluid administration and attempting to use diuretics to achieve a negative fluid balance in post– cardiac surgery patients with ALI/ARDS.
Corticosteroids There has been substantial interest in using corticosteroids to attenuate the inflammation and fibrosis associated with ARDS [59]. A randomized trial of methylprednisolone versus placebo in ARDS patients demonstrated an increase in the number of ventilator-free days, but no improvement in mortality [60]. In cardiac surgical patients, intraoperative corticosteroids have been associated with increased alveolar-arterial oxygen gradients and delayed tracheal extubation [61, 62]. Steroids can also cause hyperglycemia, which is linked to an increased risk of sternal wound infections. We, therefore, do not recommend steroids to treat ARDS in cardiac surgical patients.
Neuromuscular Blockade In severe ARDS (P:F ratio ⬍150), initiation of neuromuscular blockade may improve survival [63]. Patients with severe ARDS for less than 48 hours were randomly allocated to treatment with either cisatracurium (15 mg bolus followed by continuous infusion of 37.5 mg/h for 48 hours) or placebo. The cisatracurium group had a significantly reduced risk of death at 90 days. The mechanism of this effect and whether it is cisatracurium specific is not known. We do not routinely utilize this strategy, as it interferes with physical medicine and rehabilitation, but for cases of severe refractory ARDS, it should be considered.
Nutrition Maintaining adequate nutrition is an important component of critical care. Supplementation of enteral feeds with antioxidants and antiinflammatory fatty acids has been proposed to improve outcomes in ARDS patients. However, a double-blind, placebo-controlled study of omega-3 fatty acid, ␥-linolenic acid, and antioxidant supplementation of tube feeds in ARDS patients demonstrated no benefit and possible harm associated with the use of these supplements [64]. Early provision of enteral nutrition may be beneficial for ARDS patients [65], but there appears to be no benefit associated with trophic enteral feeding versus full enteral feeding [66]. Our practice, except for patients on significant vasoactive agents, for whom we hold enteral feeds, is to start
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tory acidosis can be tolerated. The exception to this may be patients with right-sided heart failure, in whom elevated pCO2 may increase pulmonary vascular resistance, precipitating right ventricular failure. Low tidal volume ventilation is effective and life-saving once ARDS is established, but there is also evidence that low tidal volumes may be protective in patients at risk for ARDS. In animals, high tidal volumes can induce lung injury in otherwise normal lungs [48, 49]. In humans, a safe upper limit for plateau pressure has not been identified. Tidal volume reduction in ARDS patients has been found to be beneficial regardless of the baseline plateau pressure [49]. A retrospective study of patients undergoing mechanical ventilation for non-ARDS reasons found that high tidal volume was an independent risk factor for the development of ARDS [50]. In cardiac surgical patients, Sundar and associates [51] randomly assigned patients to receive either 6 mL/kg or 10 mL/kg tidal volumes throughout the intraoperative and postoperative ICU periods. Patients in the 6 mL/kg group were more likely to be extubated at 6 hours after ICU admission (37.3% versus 20.3%; p ⫽ 0.02), and were less likely to require reintubation (1.3% versus 9.5%; p ⫽ 0.03). More recently, Lellouche and colleagues [52] prospectively classified 3,434 cardiac surgery patients into three groups depending on whether they received low (⬍10 mL/kg PBW), traditional (10 to 12 mL/kg PBW), or high (⬎12 mL/kg PBW) tidal volumes after surgery. Tidal volumes greater than 10 mL/kg PBW were associated with significantly higher rates of prolonged mechanical ventilation, hemodynamic instability, renal failure, and prolonged ICU stays. Women and obese patients were at a higher risk to receive injurious ventilator settings. Interestingly, tidal volumes were typically set based on actual body weight rather than PBW, exacerbating the problems associated with high tidal-volume ventilation. In summary, although the optimum tidal volume for postoperative cardiac surgery patients is not known, it makes sense to utilize tidal volumes of 6 to 8 mL/kg PBW in postoperative cardiac surgical patients. Oxygen has well-described toxicities at moderate and high FiO2 levels, especially in previously damaged or “primed” lungs [53, 54]. Our practice is to use the minimum FiO2 necessary to maintain adequate oxygen delivery (usually a goal SpO2 ⬎93%). We aim for a lower SpO2 target (88% to 90%) in post–lung transplant patients, whose allografts may be uniquely susceptible to oxidative stress and hyperoxic injury [55, 56].
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trophic feeds and escalate to full-dose enteral feeding as tolerated.
Early Rehabilitation Recent data suggest that the use of early physical medicine and rehabilitation in patients with acute respiratory failure can substantially decrease delirium, improve rehabilitation and functional mobility, and decrease ICU length of stay [67, 68]. While these techniques need to be adapted to the limitations of post-sternotomy patients, the benefits of early rehabilitation seem likely to apply to post– cardiac surgery patients with ARDS. Case series have reported that rehabilitation and physical therapy are possible and beneficial even for patients supported with extracorporeal membrane oxygenation (ECMO) [69].
Rescue Therapies Despite optimum management, ARDS can progress to severe refractory hypoxemia, requiring unconventional modes of mechanical ventilation or other rescue measures to sustain life.
Recruitment Maneuvers
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Recruitment maneuvers attempt to utilize transient increases in transpulmonary pressure to reopen collapsed alveoli, decreasing shunt fraction and improving hypoxemia. There are several ways to perform recruitment maneuvers; the optimum approach has not been determined. Our typical approach is to use sustained high levels of continuous positive airway pressure (eg, 35 to 40 cm H2O pressure for 30 s to 40 s) before returning to prior ventilator settings, albeit with a higher level of PEEP to maintain recruitment [70]. Other approaches involve sequentially increasing levels of PEEP while maintaining a constant level of inspiratory pressure on pressure control ventilation, followed by a stepwise decrease in PEEP [71]. The response of patients with ARDS to recruitment is extremely variable, improvements in oxygenation are short-lived, and increases in pulmonary compliance have not been seen [72]. Although recruitment maneuvers may transiently improve oxygenation, it is not known if this translates into a survival benefit [70]. Adverse consequences of recruitment maneuvers occur in more than 20% of patients and include transient desaturation, hypotension, arrhythmias, and pneumothorax. The maneuver should be terminated if oxygenation or hemodynamics are markedly impaired [73]. Increasing alveolar pressures during a recruitment maneuver can increase pulmonary vascular resistance and RV afterload, mandating caution in patients with tenuous right ventricles.
Nitric Oxide Inhaled nitric oxide (iNO) is familiar to cardiac surgeons and intensivists as a pulmonary vasodilator useful for reducing right ventricular afterload. It can also improve oxygenation in refractory ARDS. Because NO is inhaled, it results in preferential vasodilation of aerated portions
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of the lung, resulting in decreased intrapulmonary shunt and improved oxygenation. However, iNO has drawbacks, including the potential of inducing free radical injury to the lungs. Tachyphylaxis occurs, resulting in decreased effect of a given dose of iNO; improvement in oxygenation is often seen after decreasing the dose of iNO. Ranges from 0 to 40 parts per million have been used in ARDS. However, despite ample evidence that iNO improves oxygenation, repeat meta-analyses have not shown an improvement in mortality [74].
Prone Positioning Placing patients in the prone position decreases dorsal atelectasis by relieving the compressive force of the anterior mediastinal contents, leading to improved ventilation-perfusion matching and improved oxygenation. Prone positioning can improve oxygenation, but does not decrease mortality in ARDS [75]. Physicians may be reluctant to place a patient with a recent sternotomy in the prone position, but several reports suggest that prone positioning is feasible and safe in cardiac surgical patients with ARDS [76, 77].
High-Frequency Oscillatory Ventilation and Airway Pressure Release Ventilation In the face of ARDS with refractory life-threatening hypoxemia, various rescue modes of ventilation have been used. Two common modes are high-frequency oscillatory ventilation and airway pressure release ventilation. Full descriptions of these modes are beyond the scope of this review, and have been presented elsewhere [78, 79]. Both of these modes aim to increase lung recruitment through the delivery of sustained high airway pressures. High-frequency oscillatory ventilation delivers high-frequency (3 Hz to 15 Hz) subtidal volume breaths with a high sustained mean airway pressure (typically 25 cm to 40 cm H2O). Elimination of CO2 is accomplished through diffusion, turbulent mixing of gas, and collateral ventilation. As the currently available ventilator does not allow for spontaneous breathing, highfrequency oscillatory ventilation typically necessitates high levels of sedation. In contrast, airway pressure release ventilation delivers a sustained inspiratory pressure (Phigh) for a set amount of time (Thigh) with intermittent decompressions to a low pressure (Plow). Removal of CO 2 occurs through exhalation during decompression. Spontaneous breathing is possible at both Phigh and Plow, thus sedation requirements may decrease. As yet, there are no data that either of these modes improves mortality in patients with ALI/ARDS.
Extracorporeal Membrane Oxygenation Whereas the use of ECMO in medical patients with severe ARDS is limited to a few specialized centers, many cardiac surgical ICUs are capable of rapidly initiating ECMO for postoperative cardiac failure. This infrastructure and expertise can be brought to bear for severe acute respiratory failure. Both venoarterial and venovenous ECMO circuits can be used, although venovenous ECMO is often preferred in hemodynamically stable patients
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with respiratory failure. Especially in patients with incompetent aortic valves, venoarterial ECMO can be associated with left ventricular distention and persistent left atrial hypertension, leading to pulmonary edema and ongoing lung injury. Providers must ensure adequate left ventricular decompression if venoarterial ECMO is chosen. Once initiated, ECMO can allow a marked decrease, or even cessation, of ventilator support, and the initiation of “lung rest” ventilator settings. Optimum ventilator settings during ECMO support are not known, although most experts recommend a pressure- and volumelimited strategy with the application of PEEP to prevent atelectasis. The use of ECMO for acute respiratory failure has recently been comprehensively reviewed [80]. It suffices to say that in certain cases of ARDS with hypoxemia refractory to the maneuvers reviewed above, ECMO can be lifesaving.
Summary The acute respiratory distress syndrome is an important and common problem after cardiac surgery. Some populations of patients, including patients undergoing aortic surgery, pulmonary thromboendarterectomy, and lung transplantation, as well as those who receive large quantities of blood products, may be at elevated risk. Care remains supportive, but low tidal volume
Table 3. Summary of Acute Respiratory Distress Syndrome Management Management Aspect Low-tidal volume ventilation Ventilator bundle Fluid management
Neuromuscular blockade
Nutrition
Early rehabilitation
Rescue therapies
Details 6 cc/kg PBW, plateau pressure ⬍30 cm H2O Head of bed elevated, sedation vacations, DVT prophylaxis Diuresis as tolerated to achieve negative fluid balance Severe ARDS: cisatracurium 15 mg intravenous bolus followed by infusion of 37.5 mg/h for 48 hours. Early trophic feeds, with escalation to full dose as tolerated Physical and occupational therapy started shortly after admission; therapy facilitated by minimizing sedation For refractory life-threatening hypoxemia, can consider recruitment maneuvers, iNO, prone positioning, HFOV, APRV, or ECMO
See text for details. ARDS ⫽ acute respiratory distress syndrome; APRV ⫽ airway pressure release ventilation; DVT ⫽ deep venous thrombosis; ECMO ⫽ extracorporeal membrane oxygenation; HFOV ⫽ high-frequency oscillatory ventilation; iNO ⫽ inhaled nitric oxide; PBW ⫽ predicted body weight.
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ventilator strategies, careful attention to volume status, application of a standard protocol to prevent VAP, and provision of early physical rehabilitation and nutrition can help to improve patient outcomes (Table 3). Given the number of patients undergoing cardiac surgery, efforts to decrease the risk of ALI developing after cardiac surgery could significantly decrease the morbidity and mortality associated with cardiothoracic surgery.
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18. Santini F, Onorati F, Telesca M, et al. Pulsatile pulmonary perfusion with oxygenated blood ameliorates pulmonary hemodynamic and respiratory indices in low-risk coronary artery bypass patients. Eur J Cardiothorac Surg 2011;40:794 – 803. 19. Barnard ML, Matalon S. Mechanisms of extracellular reactive oxygen species injury to the pulmonary microvasculature. J Appl Physiol 1992;72:1724 –9. 20. Fink MP. Role of reactive oxygen and nitrogen species in acute respiratory distress syndrome. Curr Opin Crit Care 2002;8:6 –11. 21. Cornet AD, Kingma SD, Trof RJ, Wisselink W, Groeneveld AB. Hepatosplanchnic ischemia/reperfusion is a major determinant of lung vascular injury after aortic surgery. J Surg Res 2009;157:48 –54. 22. Adams A, Fedullo PF. Postoperative management of the patient undergoing pulmonary endarterectomy. Semin Thorac Cardiovasc Surg 2006;18:250 – 6. 23. Christie JD, Edwards LB, Kucheryavaya AY, et al. The Registry of the International Society for Heart and Lung Transplantation: twenty-seventh official adult lung and heart-lung transplant report—2010. J Heart Lung Transplant 2010;29:1104 –18. 24. Lee JC, Christie JD. Primary graft dysfunction. Clin Chest Med 2011;32:279 –93. 25. Lederer DJ, Kawut SM, Wickersham N, et al. Obesity and primary graft dysfunction after lung transplantation: the LTOG obesity study. Am J Respir Crit Care Med 2011;184: 1055– 61. 26. Daud SA, Yusen RD, Meyers BF, et al. Impact of immediate primary lung allograft dysfunction on bronchiolitis obliterans syndrome. Am J Respir Crit Care Med 2007;175:507–13. 27. Vlaar AP, Hofstra JJ, Determann RM, et al. The incidence, risk factors, and outcome of transfusion-related acute lung injury in a cohort of cardiac surgery patients: a prospective nested case-control study. Blood 2011;117:4218 –25. 28. Vlaar AP, Binnekade JM, Prins D, et al. Risk factors and outcome of transfusion-related acute lung injury in the critically ill: a nested case-control study. Crit Care Med 2010;38:771– 8. 29. Silliman CC, Ambruso DR, Boshkov LK. Transfusion-related acute lung injury. Blood 2005;105:2266 –73. 30. Gajic O, Rana R, Winters JL, et al. Transfusion-related acute lung injury in the critically ill: prospective nested casecontrol study. Am J Respir Crit Care Med 2007;176:886 –91. 31. Sachs UJ, Wasel W, Bayat B, et al. Mechanism of transfusionrelated acute lung injury induced by HLA class II antibodies. Blood 2011;117:669 –77. 32. Gajic O, Yilmaz M, Iscimen R, et al. Transfusion from male-only versus female donors in critically ill recipients of high plasma volume components. Crit Care Med 2007;35: 1645– 8. 33. Vlaar AP, Cornet AD, Hofstra JJ, et al. The effect of blood transfusion on pulmonary permeability in cardiac surgery patients: a prospective multicenter cohort study. Transfusion 2012;52:82–90. 34. Tuinman PR, Vlaar AP, Cornet AD, et al. Blood transfusion during cardiac surgery is associated with inflammation and coagulation in the lung: a case control study. Crit Care 2011;15:R59. 35. Koch C, Li L, Figueroa P, Mihaljevic T, Svensson L, Blackstone EH. Transfusion and pulmonary morbidity after cardiac surgery. Ann Thorac Surg 2009;88:1410 – 8. 36. Hajjar LA, Vincent JL, Galas FR, et al. Transfusion Requirements After Cardiac Surgery: the TRACS randomized controlled trial. JAMA 2010;304:1559 – 67. 37. Boriani G, Ferruzzi L, Corti B, Ruffato A, Gavelli G, Mattioli S. Short-term onset of fatal pulmonary toxicity in a patient treated with intravenous amiodarone for postoperative atrial fibrillation. Int J Cardiol 2012;159:e1– 4. 38. Papiris SA, Triantafillidou C, Kolilekas L, Markoulaki D, Manali ED. Amiodarone: review of pulmonary effects and toxicity. Drug Saf 2010;33:539 –58.
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39. Isiadinso I, Meshkov AB, Gaughan J, et al. Atrial arrhythmias after lung and heart-lung transplant: effects on short-term mortality and the influence of amiodarone. J Heart Lung Transplant 2011;30:37– 44. 40. Pronovost P, Needham D, Berenholtz S, et al. An intervention to decrease catheter-related bloodstream infections in the ICU. N Engl J Med 2006;355:2725–32. 41. Wald HL, Ma A, Bratzler DW, Kramer AM. Indwelling urinary catheter use in the postoperative period: analysis of the national surgical infection prevention project data. Arch Surg 2008;143:551–7. 42. Forel JM, Voillet F, Pulina D, et al. Ventilator-associated pneumonia and ICU mortality in severe ARDS patients ventilated according to a lung-protective strategy. Crit Care 2012;16:R65. 43. Rello J, Afonso E, Lisboa T, et al. A care bundle approach for prevention of ventilator-associated pneumonia. Clin Microbiol Infect 2012; February 9 (epub ahead of print). 44. Labeau SO, Van de Vyver K, Brusselaers N, Vogelaers D, Blot SI. Prevention of ventilator-associated pneumonia with oral antiseptics: a systematic review and meta-analysis. Lancet Infect Dis 2011;11:845–54. 45. Lacherade JC, De Jonghe B, Guezennec P, et al. Intermittent subglottic secretion drainage and ventilator-associated pneumonia: a multicenter trial. Am J Respir Crit Care Med 2010;182:910 –7. 46. The Acute Respiratory Distress Syndrome Network. Ventilation with lower tidal volumes as compared with traditional tidal volumes for acute lung Injury and the acute respiratory distress syndrome. N Engl J Med 2000;342:1301– 8. 47. Brower RG, Lanken PN, MacIntyre N, et al. Higher versus lower positive end-expiratory pressures in patients with the acute respiratory distress syndrome. N Engl J Med 2004;351: 327–36. 48. Webb HH, Tierney DF. Experimental pulmonary edema due to intermittent positive pressure ventilation with high inflation pressures. Protection by positive end-expiratory pressure. Am Rev Respir Dis 1974;110:556 – 65. 49. Hager DN, Krishnan JA, Hayden DL, Brower RG. Tidal volume reduction in patients with acute lung injury when plateau pressures are not high. Am J Respir Crit Care Med 2005;172:1241–5. 50. Gajic O, Dara SI, Mendez JL, et al. Ventilator-associated lung injury in patients without acute lung injury at the onset of mechanical ventilation. Crit Care Med 2004;32:1817–24. 51. Sundar S, Novack V, Jervis K, et al. Influence of low tidal volume ventilation on time to extubation in cardiac surgical patients. Anesthesiology 2011;114:1102–10. 52. Lellouche F, Dionne S, Simard S, Bussieres J, Dagenais F. High tidal volumes in mechanically ventilated patients increase organ dysfunction after cardiac surgery. Anesthesiology 2012;116:1072– 82. 53. Crapo JD, Hayatdavoudi G, Knapp MJ, Fracica PJ, Wolfe WG, Piantadosi CA. Progressive alveolar septal injury in primates exposed to 60% oxygen for 14 days. Am J Physiol 1994;267:L797– 806. 54. Sinclair SE, Altemeier WA, Matute-Bello G, Chi EY. Augmented lung injury due to interaction between hyperoxia and mechanical ventilation. Crit Care Med 2004;32:2496 –501. 55. Ellman PI, Alvis JS, Tache-Leon C, et al. Hyperoxic ventilation exacerbates lung reperfusion injury. J Thorac Cardiovasc Surg 2005;130:1440. 56. Halldorsson A, Kronon M, Allen BS, et al. Controlled reperfusion after lung ischemia: implications for improved function after lung transplantation. J Thorac Cardiovasc Surg 1998;115:415–24. 57. Wiedemann HP, Wheeler AP, Bernard GR, et al. Comparison of two fluid-management strategies in acute lung injury. N Engl J Med 2006;354:2564 –75. 58. Grams ME, Estrella MM, Coresh J, Brower RG, Liu KD. Fluid balance, diuretic use, and mortality in acute kidney injury. Clin J Am Soc Nephrol 2011;6:966 –73.
59. Meduri GU, Golden E, Freire AX, et al. Methylprednisolone infusion in early severe ARDS: results of a randomized controlled trial. Chest 2007;131:954 – 63. 60. Steinberg KP, Hudson LD, Goodman RB, et al. Efficacy and safety of corticosteroids for persistent acute respiratory distress syndrome. N Engl J Med 2006;354:1671– 84. 61. Chaney MA, Durazo-Arvizu RA, Nikolov MP, Blakeman BP, Bakhos M. Methylprednisolone does not benefit patients undergoing coronary artery bypass grafting and early tracheal extubation. J Thorac Cardiovasc Surg 2001;121:561–9. 62. Chaney MA, Nikolov MP, Blakeman B, Bakhos M, Slogoff S. Pulmonary effects of methylprednisolone in patients undergoing coronary artery bypass grafting and early tracheal extubation. Anesth Analg 1998;87:27–33. 63. Papazian L, Forel JM, Gacouin A, et al. Neuromuscular blockers in early acute respiratory distress syndrome. N Engl J Med 2010;363:1107–16. 64. Rice TW, Wheeler AP, Thompson BT, deBoisblanc BP, Steingrub J, Rock P. Enteral omega-3 fatty acid, gamma-linolenic acid, and antioxidant supplementation in acute lung injury. JAMA 2011;306:1574 – 81. 65. Doig GS, Heighes PT, Simpson F, Sweetman EA, Davies AR. Early enteral nutrition, provided within 24 h of injury or intensive care unit admission, significantly reduces mortality in critically ill patients: a meta-analysis of randomised controlled trials. Intensive Care Med 2009;35:2018 –27. 66. Rice TW, Wheeler AP, Thompson BT, et al. Initial trophic versus full enteral feeding in patients with acute lung injury: the EDEN randomized trial. JAMA 2012;307:795– 803. 67. Needham DM, Korupolu R, Zanni JM, et al. Early physical medicine and rehabilitation for patients with acute respiratory failure: a quality improvement project. Arch Phys Med Rehabil 2010;91:536 – 42. 68. Zanni JM, Korupolu R, Fan E, et al. Rehabilitation therapy and outcomes in acute respiratory failure: an observational pilot project. J Crit Care 2010;25:254 – 62. 69. Turner DA, Cheifetz IM, Rehder KJ, et al. Active rehabilitation and physical therapy during extracorporeal membrane
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oxygenation while awaiting lung transplantation—a practical approach. Crit Care Med 2011;39:2593– 8. Lapinsky SE, Mehta S. Bench-to-bedside review: recruitment and recruiting maneuvers. Crit Care 2005;9:60 –5. Hodgson CL, Tuxen DV, Bailey MJ, et al. A positive response to a recruitment maneuver with PEEP titration in patients with ARDS, regardless of transient oxygen desaturation during the maneuver. J Intensive Care Med 2011;26:41–9. Brower RG, Morris A, MacIntyre N, et al. Effects of recruitment maneuvers in patients with acute lung injury and acute respiratory distress syndrome ventilated with high positive end-expiratory pressure. Crit Care Med 2003;31:2592–7. Fan E, Checkley W, Stewart TE, et al. Complications from recruitment maneuvers in patients with acute lung injury: secondary analysis from the Lung Open Ventilation Study. Respir Care 2012;57:1842–9. Adhikari NK, Burns KE, Friedrich JO, Granton JT, Cook DJ, Meade MO. Effect of nitric oxide on oxygenation and mortality in acute lung injury: systematic review and metaanalysis. BMJ 2007;334:779. Alsaghir AH, Martin CM. Effect of prone positioning in patients with acute respiratory distress syndrome: a metaanalysis. Crit Care Med 2008;36:603–9. Maillet JM, Thierry S, Brodaty D. Prone positioning and acute respiratory distress syndrome after cardiac surgery: a feasibility study. J Cardiothorac Vasc Anesth 2008;22:414 –7. Brussel T, Hachenberg T, Roos N, Lemzem H, Konertz W, Lawin P. Mechanical ventilation in the prone position for acute respiratory failure after cardiac surgery. J Cardiothorac Vasc Anesth 1993;7:541– 6. Fessler HE, Derdak S, Ferguson ND, et al. A protocol for high-frequency oscillatory ventilation in adults: results from a roundtable discussion. Crit Care Med 2007;35:1649 –54. Maung AA, Kaplan LJ. Airway pressure release ventilation in acute respiratory distress syndrome. Crit Care Clin 2011; 27:501–9. Brodie D, Bacchetta M. Extracorporeal membrane oxygenation for ARDS in adults. N Engl J Med 2011;365:1905–14.
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As many as 20% of patients undergoing cardiac surgery will have acute respiratory distress syndrome during the perioperative period, with a mortality as high as 80%. If patients at risk can be identified, preventative measures can be taken and may improve outcomes. Care for patients with acute respiratory distress syndrome is supportive, with low tidal volume ventilation being the mainstay of therapy. Careful fluid management, minimi-
zation of blood product transfusion, appropriate nutrition, and early physical rehabilitation may improve outcomes. In cases of refractory hypoxemia, rescue therapies such as recruitment maneuvers, high-frequency oscillatory ventilation, and extracorporeal membrane oxygenation may preserve life. (Ann Thorac Surg 2013;95:1122–9) © 2013 by The Society of Thoracic Surgeons
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Risk Factors and Specific Etiologies
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he acute respiratory distress syndrome (ARDS) is a devastating syndrome of acute hypoxemic respiratory failure and bilateral pulmonary infiltrates [1–3]. The recently published 2012 Berlin Definition of ARDS [3] describes ARDS as hypoxemia, occurring within 1 week of a known clinical insult or new or worsening respiratory symptoms, associated with bilateral opacities on chest imaging not fully explained by pleural effusions, atelectasis, or nodules, and not fully explained by cardiac failure or fluid overload. Formerly described as a subset of acute lung injury (ALI), with ALI describing patients with a ratio of PaO2 to fraction of inspired oxygen (FiO2) equal to or less than 300, and ARDS reserved for patients with PaO2:FiO2 equal to or less than 200, ARDS is now divided into three categories: mild ARDS (200 mm Hg ⬍ PaO2:FiO2 ⱕ300 mm Hg with PEEP [positive endexpiratory pressure] or continuous positive airway pressure ⱖ5 cm H2O); moderate ARDS (100 mm Hg ⬍ PaO2:FiO2 ⱕ200 mm Hg with PEEP ⱖ5 cm H2O); and severe ARDS (PaO2:FiO2 ⱕ100 mm Hg with PEEP ⱖ5 cm H2O). Cardiac surgery is a known risk factor for ARDS; of the more than 300,000 patients who undergo cardiac surgery every year in the United States, as many as 20% will have ARDS [4 –9]. The mortality associated with ARDS approaches 40% in the general population, but among post– cardiac surgery patients, mortality may be as high as 80% [10, 11]. Survivors may have increased intensive care unit (ICU) and hospital length of stay, as well as substantial long-term physical and psychological morbidity [12]. An understanding of ARDS risk factors and the principles of its management may help both to prevent ARDS after cardiac surgery and to improve patient outcomes after ARDS has occurred. Address correspondence to Dr Stephens, Division of Pulmonary and Critical Care Medicine, 5501 Hopkins Bayview Circle, 4th Flr, Asthma and Allergy Center, Baltimore, MD 21224; e-mail: [email protected].
© 2013 by The Society of Thoracic Surgeons Published by Elsevier Inc
Many of the techniques and sequelae of cardiac surgery increase the risk of ARDS. Cardiopulmonary bypass (CPB), which induces a systemic inflammatory state, and pulmonary ischemia-reperfusion (IR) injury have both been associated with ARDS. The use of allogenic blood products exposes patients to the risk of transfusionrelated acute lung injury (TRALI). Pharmaceuticals such as amiodarone have the capacity to induce drug-related ALI. Finally, all patients undergoing cardiac surgery are intubated, sedated, and mechanically ventilated, exposing them to the risks of aspiration, ventilator-associated pneumonia, and ventilator-induced lung injury.
Surgical Procedure Performed Type of surgery greatly influences the risk of developing ARDS. Among all patients undergoing cardiac surgery, the risk of ARDS may be as high as 10%, but that risk is increased to nearly 17% among patients undergoing aortic surgery [8]. Longer bypass times, the use of hypothermic circulatory arrest, and requirement for more blood products may all play roles in increasing risk. Emergent repair of aortic catastrophe carries an even higher risk of respiratory failure—nearly 50% (13). High rates of respiratory failure (more than 20%) have also been reported after left ventricular assist device placement [14], although not all of these failures may be due to ARDS. Postoperative respiratory failure is associated with higher 1-year mortality among ventricular assist device recipients [14].
Cardiopulmonary Bypass Although the development of CPB made open heart surgery possible, saving hundreds of thousands of lives, the circulation of blood through an artificial extracorporeal circuit can incite systemic and pulmonary injury. During CPB, bronchial artery flow is maintained, but 0003-4975/$36.00 http://dx.doi.org/10.1016/j.athoracsur.2012.10.024
Abbreviations and Acronyms ALI ⫽ acute lung injury ARDS ⫽ acute respiratory distress syndrome CPB ⫽ cardiopulmonary bypass ECMO ⫽ extracorporeal membrane oxygenation FiO2 ⫽ fraction of inspired oxygen ICU ⫽ intensive care unit IR ⫽ ischemia-reperfusion PBW ⫽ predicted body weight PEEP ⫽ positive end-expiratory pressure PGD ⫽ primary graft dysfunction TRALI ⫽ transfusion-related acute lung injury VAP ⫽ ventilator-associated pneumonia VT ⫽ tidal volume
pulmonary arterial flow is markedly decreased. Concurrently, ventilation of the lungs is typically stopped to improve surgical exposure and field stability. The absence of ventilation in combination with reduced blood flow to the lungs may increase susceptibility to pulmonary injury. Cardiopulmonary bypass also initiates a profound systemic inflammatory cascade that can lead to pulmonary injury. As many as 60% of patients have increased pulmonary vascular permeability during CPB [15]. Polymorphisms in the interleukin-6 and interleukin-18 genes may predispose toward ALI after CPB [16, 17]. Ameliorating the injurious effects of CPB is an area of active investigation [18].
Ischemia-Reperfusion Transient ischemia and subsequent reperfusion of the lungs can result in the production of injurious reactive oxygen species [19, 20]. Some degree of pulmonary IR injury predictably occurs during and after CPB and during resuscitation from shock. Longer periods of pulmonary ischemia and subsequent IR injury occur during procedures such as pulmonary endarterectomy, hypothermic circulatory arrest, and lung transplantation. Extrapulmonary IR can also contribute to lung injury: in aortic procedures, hepatosplanchnic IR releases inflammatory mediators that contribute to the increase in pulmonary vascular permeability [21].
Pulmonary Endarterectomy Pulmonary endarterectomy for chronic thromboembolic pulmonary hypertension can dramatically improve functional status. However, these patients are uniquely susceptible to reperfusion-induced high-permeability pulmonary edema, resulting in profound shunt physiology and severe hypoxemia. Limited to portions of the lung from which proximal vascular obstruction has been removed, this generally occurs in the first 72 hours postoperatively. The management of patients after pulmonary endarterectomy has recently been reviewed [22].
Lung Transplantation Of the approximately 2,700 patients in the United States who undergo lung transplantation each year [23], 10% to
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25% will experience primary graft dysfunction (PGD). Primary graft dysfunction is a form of ARDS that occurs in the first 72 hours after lung transplantation and confers a significant increase in mortality [24]. Primary graft dysfunction is multifactorial in etiology; IR injury to the pulmonary endothelium and physiologic changes associated with donor brain death are thought to be of primary importance [24]. Obesity is a risk factor for PGD, as is the use of CPB, ventilator-induced lung injury, and large volume transfusion of blood products [24, 25]. Importantly, although PGD typically improves within 3 to 5 days if the patient survives, the occurrence of PGD increases the risk of bronchiolitis obliterans syndrome and allograft failure [26]. Prevention of this entity is essential to the long-term survival of lung transplant recipients.
Transfusion-Related Acute Lung Injury Cardiac surgical patients frequently require blood product support for anemia, thrombocytopenia, or coagulopathy. All transfusions carry the risk of TRALI, the leading cause of transfusion-related morbidity and mortality. Transfusion-related acute lung injury has been linked to longer ventilator times and increased ICU length of stay [27, 28]. Defined as the acute onset of hypoxia and bilateral pulmonary infiltrates within 6 hours of a transfusion, TRALI can present with tachypnea, cyanosis, dyspnea, and fever [29]. Mortality ranges from 5% to 25%. Cardiac surgery has been identified as an independent risk factor for TRALI [28]. The incidence of TRALI has been reported to be 2.5% among cardiac surgical patients [27]; that is probably an underestimate [30]. TRALI is likely immunemediated, as donor-related antileukocyte antibodies or antibody-producing donor leukocytes trigger neutrophil activation with resultant pulmonary endothelial damage and high-permeability edema [27, 31]. Transfusion of plasma-rich products such as fresh frozen plasma and platelets, especially from multiparous female donors, carries a higher risk of TRALI [27, 30, 32]. Transfusion of red cells is not harmless, and increases pulmonary permeability in a dose-dependent fashion [33, 34]. In addition, TRALI may be more likely in the presence of other ALI risk factors (30). Transfusion can also lead to transfusion-associated circulatory overload, which also develops acutely but responds rapidly to diuresis [29]. Transfusion-associated circulatory overload and TRALI can coexist, leading to mixed hydrostatic and permeability edema. Even in the absence of TRALI or transfusion-associated circulatory overload, transfusion increases pulmonary complications after cardiac surgery [35]. A restrictive transfusion strategy, targeting a hemoglobin of 7 to 8 mg/dL rather than 10 to 12 mg/dL, may help avoid the complications of transfusions. Although the incidence of lung injury was not a specific endpoint, the safety of a restrictive transfusion strategy after cardiac surgery was shown in a 500-patient randomized controlled trial [36].
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Table 1. Modifiable Acute Respiratory Distress Syndrome Risk Factors and Preventative Measures Risk Factor Cardiopulmonary bypass Aortic surgery Ventricular assist device insertion Transfusion of blood products Ventilator-associated lung injury Ventilator-associated pneumonia
Preventative Measure None None None Minimize blood product administration Low-tidal volume ventilation, early extubation Head of bed at 30 degrees or more, chlorhexidine mouth cleansing, sedation vacations, subglottic drainage of secretions, early extubation
Drug Toxicity
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Many pharmaceuticals have been reported to induce acute lung injury. In cardiac surgical patients, amiodarone, routinely used for prophylaxis and treatment of arrhythmias, is a potential cause of drug-induced lung injury. Amiodarone has well-described pulmonary toxicity, which can present as fulminant ARDS after only brief treatment courses (5 to 10 days) [37] or as subacute respiratory failure. If this entity is suspected, amiodarone should be stopped immediately. Steroids may be of some use [38]. Amiodarone has also been associated with increased mortality among lung and heart-lung transplant patients, and should be used with caution in these populations [39]. Amiodarone lung toxicity has been comprehensively reviewed [38] (www.pneumotox.com is an excellent resource on medication-associated lung injury).
Prevention and Management Identification of Patients at Risk The identification of patients at high risk for ARDS is an area of active investigation. If at-risk patients can be identified, targeted preventative measures may decrease the likelihood of ARDS developing (Table 1). Such measures could include avoiding unnecessary transfusions, appropriate mechanical ventilator settings, and early extubation, before ventilator-induced lung injury and ventilator-associated pneumonia (VAP) can occur. All cardiac surgical patients are at risk for ARDS, with patients undergoing aortic surgery, lung transplantation, and emergent procedures at even higher risk [8]. Gajic and associates [8] recently proposed a lung injury prediction score, which includes such factors as the presence of shock, sepsis, high-risk surgery, obesity, hypoalbuminemia, administration of high levels of FiO2, acidosis, and diabetes mellitus, all relevant to cardiac surgical patients. Smartphone-based applications can predict prolonged postoperative ventilatory times (eg, CV Surgery Ventilator Risk, Edward Bender, MD).
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General Care Fundamental critical care principals are vital to the care of all post– cardiac surgery patients. As sepsis is a cause of ARDS, efforts to prevent ICU-acquired infections are mandatory. To prevent central line associated bloodstream infections, central venous catheters should be inserted sterilely with full barrier precautions, and removed as soon as no longer needed [40]. Urinary catheters should be removed as soon as feasible [41]. Ventilator-associated pneumonia is a risk factor for ARDS and increases mortality when it develops in patients with preexisting ARDS [42]. The use of “ventilator bundles” consisting of measures such as semirecumbent (head of bed at 30 degrees or higher) positioning, mouth cleansing with chlorhexidine, and minimizing sedation have been shown to decrease the incidence of ventilator-associated pneumonias [43, 44]. Endotracheal tubes that permit intermittent drainage of subglottic secretions may also decrease the rate of VAP [45].
Mechanical Ventilator Strategies The cornerstone of ALI/ARDS management is lungprotective mechanical ventilation with low tidal volumes. A landmark ARDS Network study compared ventilation with tidal volumes of 6 mL/kg predicted body weight (PBW) to tidal volumes (VT) of 12 mL/kg PBW in patients with ARDS. A volume-assist control mode was used, and tidal volumes were adjusted to keep the end-inspiratory plateau pressure less than 30 cm H2O and 50 cm H2O, respectively. The PEEP and FiO2 were set according to a predetermined protocol. Mortality was 31% in the low VT group versus 39.8% in the traditional VT group [46]. Protective ventilation can also be achieved with pressure control modes, with the inspiratory pressure kept below 30 cm H2O and adjusted to target a VT of 6 mL/kg PBW. Tidal volumes should be set to PBW, which is determined by sex and height, not actual body weight (Table 2). We recommend that PEEP and FiO2 be set according to the ARDS Network scale. Patients with diffuse symmetric infiltrates may have a more robust oxygenation response to PEEP than patients with unilateral or focal infiltrates. Conversely, higher PEEP can decrease cardiac output, cause pulmonary overdistention, increase pulmonary vascular resistance, and increase dead space [47]. Application of PEEP, therefore, requires a judicious approach and close monitoring. In general, oxygen and PEEP should be titrated to maintain a PaO2 greater than 55 to 60 mm Hg, or SpO2 greater than 88%, although some clinical scenarios (eg, neurologic injury) mandate a higher oxygenation goal. Use of low tidal volumes may require increases in respiratory rate to maintain adequate ventilation; in general a mild-to-moderate respiraTable 2. Equations to Calculate Predicted Body Weight Males 50 ⫹ 0.91 (height in centimeters ⫺ 152.4)
Females 45.5 ⫹ 0.91 (height in centimeters ⫺ 152.4)
Published by the ARDS Network [46].
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Fluid Management Cardiac surgical patients routinely become significantly volume overloaded as a consequence of cardiopulmonary bypass and intraoperative and postoperative fluid resuscitation. Increased intravascular hydrostatic pressure can worsen the capillary leak of acute lung injury. In a trial of conservative or liberal fluid management in ARDS patients [57], patients randomly assigned to the conservative strategy had a cumulative fluid balance of ⫺136 ⫾ 491 mL over 7 days, compared with a balance of ⫹6992 ⫾ 502 mL in patients in the liberal strategy group.
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The conservative group had improved lung injury scores and oxygenation indices, lower plateau pressures, required less PEEP, and had more ventilator-free days and more ICU-free days. As patients with ARDS often have acute kidney injury, clinicians often need to decide whether to administer diuretic therapy. A study of patients with ARDS and acute kidney injury found that a positive fluid balance was associated with an increased risk of mortality, and that diuretic therapy after acute kidney injury improved mortality among patients with ARDS [58]. Based on these studies, we recommend minimizing fluid administration and attempting to use diuretics to achieve a negative fluid balance in post– cardiac surgery patients with ALI/ARDS.
Corticosteroids There has been substantial interest in using corticosteroids to attenuate the inflammation and fibrosis associated with ARDS [59]. A randomized trial of methylprednisolone versus placebo in ARDS patients demonstrated an increase in the number of ventilator-free days, but no improvement in mortality [60]. In cardiac surgical patients, intraoperative corticosteroids have been associated with increased alveolar-arterial oxygen gradients and delayed tracheal extubation [61, 62]. Steroids can also cause hyperglycemia, which is linked to an increased risk of sternal wound infections. We, therefore, do not recommend steroids to treat ARDS in cardiac surgical patients.
Neuromuscular Blockade In severe ARDS (P:F ratio ⬍150), initiation of neuromuscular blockade may improve survival [63]. Patients with severe ARDS for less than 48 hours were randomly allocated to treatment with either cisatracurium (15 mg bolus followed by continuous infusion of 37.5 mg/h for 48 hours) or placebo. The cisatracurium group had a significantly reduced risk of death at 90 days. The mechanism of this effect and whether it is cisatracurium specific is not known. We do not routinely utilize this strategy, as it interferes with physical medicine and rehabilitation, but for cases of severe refractory ARDS, it should be considered.
Nutrition Maintaining adequate nutrition is an important component of critical care. Supplementation of enteral feeds with antioxidants and antiinflammatory fatty acids has been proposed to improve outcomes in ARDS patients. However, a double-blind, placebo-controlled study of omega-3 fatty acid, ␥-linolenic acid, and antioxidant supplementation of tube feeds in ARDS patients demonstrated no benefit and possible harm associated with the use of these supplements [64]. Early provision of enteral nutrition may be beneficial for ARDS patients [65], but there appears to be no benefit associated with trophic enteral feeding versus full enteral feeding [66]. Our practice, except for patients on significant vasoactive agents, for whom we hold enteral feeds, is to start
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tory acidosis can be tolerated. The exception to this may be patients with right-sided heart failure, in whom elevated pCO2 may increase pulmonary vascular resistance, precipitating right ventricular failure. Low tidal volume ventilation is effective and life-saving once ARDS is established, but there is also evidence that low tidal volumes may be protective in patients at risk for ARDS. In animals, high tidal volumes can induce lung injury in otherwise normal lungs [48, 49]. In humans, a safe upper limit for plateau pressure has not been identified. Tidal volume reduction in ARDS patients has been found to be beneficial regardless of the baseline plateau pressure [49]. A retrospective study of patients undergoing mechanical ventilation for non-ARDS reasons found that high tidal volume was an independent risk factor for the development of ARDS [50]. In cardiac surgical patients, Sundar and associates [51] randomly assigned patients to receive either 6 mL/kg or 10 mL/kg tidal volumes throughout the intraoperative and postoperative ICU periods. Patients in the 6 mL/kg group were more likely to be extubated at 6 hours after ICU admission (37.3% versus 20.3%; p ⫽ 0.02), and were less likely to require reintubation (1.3% versus 9.5%; p ⫽ 0.03). More recently, Lellouche and colleagues [52] prospectively classified 3,434 cardiac surgery patients into three groups depending on whether they received low (⬍10 mL/kg PBW), traditional (10 to 12 mL/kg PBW), or high (⬎12 mL/kg PBW) tidal volumes after surgery. Tidal volumes greater than 10 mL/kg PBW were associated with significantly higher rates of prolonged mechanical ventilation, hemodynamic instability, renal failure, and prolonged ICU stays. Women and obese patients were at a higher risk to receive injurious ventilator settings. Interestingly, tidal volumes were typically set based on actual body weight rather than PBW, exacerbating the problems associated with high tidal-volume ventilation. In summary, although the optimum tidal volume for postoperative cardiac surgery patients is not known, it makes sense to utilize tidal volumes of 6 to 8 mL/kg PBW in postoperative cardiac surgical patients. Oxygen has well-described toxicities at moderate and high FiO2 levels, especially in previously damaged or “primed” lungs [53, 54]. Our practice is to use the minimum FiO2 necessary to maintain adequate oxygen delivery (usually a goal SpO2 ⬎93%). We aim for a lower SpO2 target (88% to 90%) in post–lung transplant patients, whose allografts may be uniquely susceptible to oxidative stress and hyperoxic injury [55, 56].
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trophic feeds and escalate to full-dose enteral feeding as tolerated.
Early Rehabilitation Recent data suggest that the use of early physical medicine and rehabilitation in patients with acute respiratory failure can substantially decrease delirium, improve rehabilitation and functional mobility, and decrease ICU length of stay [67, 68]. While these techniques need to be adapted to the limitations of post-sternotomy patients, the benefits of early rehabilitation seem likely to apply to post– cardiac surgery patients with ARDS. Case series have reported that rehabilitation and physical therapy are possible and beneficial even for patients supported with extracorporeal membrane oxygenation (ECMO) [69].
Rescue Therapies Despite optimum management, ARDS can progress to severe refractory hypoxemia, requiring unconventional modes of mechanical ventilation or other rescue measures to sustain life.
Recruitment Maneuvers
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Recruitment maneuvers attempt to utilize transient increases in transpulmonary pressure to reopen collapsed alveoli, decreasing shunt fraction and improving hypoxemia. There are several ways to perform recruitment maneuvers; the optimum approach has not been determined. Our typical approach is to use sustained high levels of continuous positive airway pressure (eg, 35 to 40 cm H2O pressure for 30 s to 40 s) before returning to prior ventilator settings, albeit with a higher level of PEEP to maintain recruitment [70]. Other approaches involve sequentially increasing levels of PEEP while maintaining a constant level of inspiratory pressure on pressure control ventilation, followed by a stepwise decrease in PEEP [71]. The response of patients with ARDS to recruitment is extremely variable, improvements in oxygenation are short-lived, and increases in pulmonary compliance have not been seen [72]. Although recruitment maneuvers may transiently improve oxygenation, it is not known if this translates into a survival benefit [70]. Adverse consequences of recruitment maneuvers occur in more than 20% of patients and include transient desaturation, hypotension, arrhythmias, and pneumothorax. The maneuver should be terminated if oxygenation or hemodynamics are markedly impaired [73]. Increasing alveolar pressures during a recruitment maneuver can increase pulmonary vascular resistance and RV afterload, mandating caution in patients with tenuous right ventricles.
Nitric Oxide Inhaled nitric oxide (iNO) is familiar to cardiac surgeons and intensivists as a pulmonary vasodilator useful for reducing right ventricular afterload. It can also improve oxygenation in refractory ARDS. Because NO is inhaled, it results in preferential vasodilation of aerated portions
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of the lung, resulting in decreased intrapulmonary shunt and improved oxygenation. However, iNO has drawbacks, including the potential of inducing free radical injury to the lungs. Tachyphylaxis occurs, resulting in decreased effect of a given dose of iNO; improvement in oxygenation is often seen after decreasing the dose of iNO. Ranges from 0 to 40 parts per million have been used in ARDS. However, despite ample evidence that iNO improves oxygenation, repeat meta-analyses have not shown an improvement in mortality [74].
Prone Positioning Placing patients in the prone position decreases dorsal atelectasis by relieving the compressive force of the anterior mediastinal contents, leading to improved ventilation-perfusion matching and improved oxygenation. Prone positioning can improve oxygenation, but does not decrease mortality in ARDS [75]. Physicians may be reluctant to place a patient with a recent sternotomy in the prone position, but several reports suggest that prone positioning is feasible and safe in cardiac surgical patients with ARDS [76, 77].
High-Frequency Oscillatory Ventilation and Airway Pressure Release Ventilation In the face of ARDS with refractory life-threatening hypoxemia, various rescue modes of ventilation have been used. Two common modes are high-frequency oscillatory ventilation and airway pressure release ventilation. Full descriptions of these modes are beyond the scope of this review, and have been presented elsewhere [78, 79]. Both of these modes aim to increase lung recruitment through the delivery of sustained high airway pressures. High-frequency oscillatory ventilation delivers high-frequency (3 Hz to 15 Hz) subtidal volume breaths with a high sustained mean airway pressure (typically 25 cm to 40 cm H2O). Elimination of CO2 is accomplished through diffusion, turbulent mixing of gas, and collateral ventilation. As the currently available ventilator does not allow for spontaneous breathing, highfrequency oscillatory ventilation typically necessitates high levels of sedation. In contrast, airway pressure release ventilation delivers a sustained inspiratory pressure (Phigh) for a set amount of time (Thigh) with intermittent decompressions to a low pressure (Plow). Removal of CO 2 occurs through exhalation during decompression. Spontaneous breathing is possible at both Phigh and Plow, thus sedation requirements may decrease. As yet, there are no data that either of these modes improves mortality in patients with ALI/ARDS.
Extracorporeal Membrane Oxygenation Whereas the use of ECMO in medical patients with severe ARDS is limited to a few specialized centers, many cardiac surgical ICUs are capable of rapidly initiating ECMO for postoperative cardiac failure. This infrastructure and expertise can be brought to bear for severe acute respiratory failure. Both venoarterial and venovenous ECMO circuits can be used, although venovenous ECMO is often preferred in hemodynamically stable patients
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with respiratory failure. Especially in patients with incompetent aortic valves, venoarterial ECMO can be associated with left ventricular distention and persistent left atrial hypertension, leading to pulmonary edema and ongoing lung injury. Providers must ensure adequate left ventricular decompression if venoarterial ECMO is chosen. Once initiated, ECMO can allow a marked decrease, or even cessation, of ventilator support, and the initiation of “lung rest” ventilator settings. Optimum ventilator settings during ECMO support are not known, although most experts recommend a pressure- and volumelimited strategy with the application of PEEP to prevent atelectasis. The use of ECMO for acute respiratory failure has recently been comprehensively reviewed [80]. It suffices to say that in certain cases of ARDS with hypoxemia refractory to the maneuvers reviewed above, ECMO can be lifesaving.
Summary The acute respiratory distress syndrome is an important and common problem after cardiac surgery. Some populations of patients, including patients undergoing aortic surgery, pulmonary thromboendarterectomy, and lung transplantation, as well as those who receive large quantities of blood products, may be at elevated risk. Care remains supportive, but low tidal volume
Table 3. Summary of Acute Respiratory Distress Syndrome Management Management Aspect Low-tidal volume ventilation Ventilator bundle Fluid management
Neuromuscular blockade
Nutrition
Early rehabilitation
Rescue therapies
Details 6 cc/kg PBW, plateau pressure ⬍30 cm H2O Head of bed elevated, sedation vacations, DVT prophylaxis Diuresis as tolerated to achieve negative fluid balance Severe ARDS: cisatracurium 15 mg intravenous bolus followed by infusion of 37.5 mg/h for 48 hours. Early trophic feeds, with escalation to full dose as tolerated Physical and occupational therapy started shortly after admission; therapy facilitated by minimizing sedation For refractory life-threatening hypoxemia, can consider recruitment maneuvers, iNO, prone positioning, HFOV, APRV, or ECMO
See text for details. ARDS ⫽ acute respiratory distress syndrome; APRV ⫽ airway pressure release ventilation; DVT ⫽ deep venous thrombosis; ECMO ⫽ extracorporeal membrane oxygenation; HFOV ⫽ high-frequency oscillatory ventilation; iNO ⫽ inhaled nitric oxide; PBW ⫽ predicted body weight.
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ventilator strategies, careful attention to volume status, application of a standard protocol to prevent VAP, and provision of early physical rehabilitation and nutrition can help to improve patient outcomes (Table 3). Given the number of patients undergoing cardiac surgery, efforts to decrease the risk of ALI developing after cardiac surgery could significantly decrease the morbidity and mortality associated with cardiothoracic surgery.
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