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Mechanical ventilation in cardiac surgery
Current Anaesthesia & Critical Care 21 (2010) 250e254
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FOCUS ON: MECHANICAL VENTILATION IN THE OR
Mechanical ventilation in cardiac surgery Rafael Badenes*, F. Javier Belda, Gerardo Aguilar Department Anesthesiology and Critical Care, Hospital Clinic Universitari, Valencia, Spain
s u m m a r y Keywords: Postoperative pulmonary dysfunction Mechanical ventilation Open lung approach Cardiac surgery
Postoperative pulmonary dysfunction (PPD) is a frequent complication after cardiac surgery. Its pathogenesis is related to pulmonary inflammation, but this appears to be secondary to multiple etiological factors, including the surgical procedure itself, extra corporeal circulation (ECC), ischemia-reperfusion injury, and mechanical ventilation (MV). On the other hand, the presence of atelectasis remains one of the principal causes of PPD. The open lung approach (OLA) is a protective ventilation strategy, typically initiated after orotracheal intubation and maintained until extubation of the patient. Compared to a conventional ventilation strategy, OLA improves gas exchange parameters, induces a minor elevation of inflammatory mediators, and retains more residual functional capacity. Finally, recent studies have shown that the addition of low frequency ventilation during ECC can decrease the incidence of PPD after cardiac surgery. Ó 2010 Elsevier Ltd. All rights reserved.
1. Introduction Postoperative pulmonary dysfunction (PPD) is a common complication after cardiac surgery,1 but it is not clear what mechanisms are involved in its development. Therefore, it is unknown which therapeutic maneuvers might reduce the incidence of PPD. The manifestations of PPD include a frequent presence of pleural effusion (27e95%)2 and atelectasis (16.6e88%),3 detectable postoperative hypoxemia without clinical symptoms (3e10%),4 and the development of acute respiratory distress syndrome (ARDS). The incidence of ARDS is low (0.5e1.7%),5 but it is associated with high mortality (50e90%).6 40% of patients readmitted into intensive care units (ICU) present with respiratory failure.7 Chung et al8 found that, after cardiac surgery, a high inspiratory oxygen requirement during the ICU stay was related to increasing risk of readmission (odds ratio 1.09, p < 0.05). In addition, after cardiac surgery, the systemic inflammatory response was typically associated with a moderate pulmonary component, characterized by reduced pulmonary compliance, pulmonary edema, an increased intrapulmonary shunt fraction, and reduced functional residual capacity (FRC).9
* Corresponding author. GV Fernando el Católico 5-5, 46008, Valencia, Spain. Tel.: þ34696819532. E-mail address: [email protected] (R. Badenes). 0953-7112/$ e see front matter Ó 2010 Elsevier Ltd. All rights reserved. doi:10.1016/j.cacc.2010.07.006
1.1. Mechanisms involved in the development of PPD after cardiac surgery 1.1.1. Mechanical ventilation (MV) with general anesthesia After cardiac surgery, the FRC typically diminishes by 40e50% during the first hours after extubation10; in contrast to other types of surgery where FRC is reduced by about 20% after extubation.11 The exaggerated effect observed after cardiac surgery remains unexplained, but seems to be related to pulmonary inflammation. Many etiological factors play an important role in this effect, including extra corporeal circulation (ECC), injuries due to ischemia-reperfusion, the surgical intervention, and MV. The presence of atelectasis is one of the principal causes of PPD,12 and there is a correlation between the amount of atelectasis and the intrapulmonary shunt.13 Pulmonary inflammation induced by MV is the result of combined mechanical and biological trauma. Mechanical trauma refers to the stress related to alveolar overdistension due to large tidal volumes (volutrauma) or pressures (barotrauma). This stress causes epithelial injury, loss of epithelial integrity, and edema. In particular, stress is produced in the presence of large areas of atelectasis, when tidal volume inflates fewer areas of alveoli. Biological trauma occurs upon ventilating normal lungs with high inspiratory volumes, which triggers local and systemic inflammatory responses. Consequently, the release of cytokines from a variety of lung cells alters cellular pathways that are important for normal function of tissues and organs; this effect has been called biotrauma.
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The development of atelectasis is closely related to the loss of surfactant and to repetitive closing and re-opening of the alveoli. Atelectasis is a primary factor in the development of pulmonary inflammation.14 When dependent parts of the lung are atelectatic when the lung is exposed to high ventilating pressures, the traction forces applied to junctional tissues can be very high; for example, the traction force can approximate 140 cm H2O with an alveolar pressure of 30 cm H2O.15 This “stress induced failure” of the alveolar capillary membrane is responsible for increased microvascular permeability, edema, and an influx of plasmatic proteins, which16,17 inactivate the surfactant. Dreyfuss et al. demonstrated that the determining factor for pulmonary injury and inflammation was ventilation with high tidal volumes (producing high transpulmonary pressure), but not ventilation with high pressures (producing low transpulmonary pressure). Biotrauma results from the mechanical, or “shear” forces between the open and closed alveoli and overdistension of alveoli, which provoke inflammatory responses at the pulmonary level. However, it is not clear how mechanical forces are translated into the biochemical signals that produce biotrauma. Theories proposed have implied mechanoreceptors, stretch-sensitive channels, activation of the inflammatory cascade,14 and activation of the transcription of the nuclear factor kappa.18 Many experimental studies have studied the relationship of mechanical distension of the alveolocapillary membrane and the production of mediators. 19e25 During MV, pulmonary endothelial cells are exposed to stress, particularly during repetitive opening and closing of alveoli in atelectatic regions, but also during changes in transluminal pressure with alveolar inflation. Mechanical stress in the alveolocapillary membrane can affect the structural proteins of the membrane, the ion channels, and the cellular cytoskeleton; subsequent changes in cellular signaling cascades can produce diverse effects, including liberation of cytokines and other mediators, activation of transcription factors, altered expression of genes and proteins, cellular division, or even cellular death.26 The exaggerated inflammatory response (production of interleukins, inflammatory mediators, etc) is not limited to the pulmonary tissues, but may cross into the systemic circulation27 and cause a systemic inflammatory response. Ranieri et al.28 confirmed previous experimental findings in patients with ARDS. The levels of tumor necrosis factor-alpha (TNFalpha), interleukin-6 (IL-6), and IL-8 in bronchoalveolar lavage (BAL) were lower with a ventilatory strategy titrated for optimal positive end-expiratory pressure (PEEP) and low tidal volumes than with a strategy that used high tidal volumes. In a multicentre study with 861 patients, ventilation with low tidal volumes (6 ml/kg) diminished plasma concentrations of IL-6 and significantly reduced the 28-day mortality of patients with ARDS. This suggested that the application of suitable ventilatory strategies clearly affected the development of an inflammatory response after cardiac surgery. Miranda et al.29 found that an open lung strategy (tidal volume, 6 ml/kg; PEEP, 14 cm H2O) applied immediately after intubation in cardiac surgery reduced the plasma levels of IL-6, IL-8, IL-10, TNFalpha, and interferon-gamma. Thus, the exaggerated pulmonary dysfunction after cardiac surgery was apparently due to two different types of stress. One was induced by MV (mechanical stress and biotrauma) and the second was the inflammatory response to the cardiac surgery. Other factors that contribute to the development of PPD after cardiac surgery include a ventilatory strategy that permits atelectasis and the setting of high volumes and low PEEP levels.30 1.1.2. Cardiovascular effects of MV It is well known that MV can have potentially adverse cardiovascular effects, depending on the ventilatory strategy. Patients with cardiovascular pathology exhibit a hemodynamic response to
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MV that depends on numerous factors, including myocardial function, the state of intravascular volume, intrathoracic pressure, pulmonary distention, intrinsic autonomic tone, etc. Moreover, many patients present with pump failure and/or valvular pathology (fundamental indications for the cardiac surgery). The MV per se, may produce changes in the right ventricle (RV) preload and afterload. Due to an increase in intrathoracic pressure, the gradient between the right atrium and the venous system may be reduced, diminishing the preload, and thus, the cardiac output of the RV. A reduction in lung volume at the end of expiration and alveolar collapse stimulate pulmonary hypoxic vasoconstriction (PHV), which diverts blood flow to areas that are better aerated.31 When alveolar collapse is prevented with PEEP, recruiting maneuvers and a protective ventilatory strategy can reduce the vascular pulmonary resistance and prevent PHV.32,33 Miranda et al. studied the effects of an open lung strategy on the RV afterload after cardiac surgery. The patients were randomized into two groups, one with the open lung strategy (high levels of PEEP, tidal volumes of 4e6 ml/kg, and frequent recruitment maneuvers) and the other with conventional MV (PEEP 5 cm H2O and tidal volumes of 6e8 ml/kg) after the surgery. No increases were observed in the RV afterload. In addition, the protective strategy group showed an improvement in the ratio of partial pressure of arterial oxygen to the fraction of inspired oxygen (PaO2/FiO2). Left ventricle (LV) afterload is defined as the end-systolic volume or as the maximum tension in the wall of the left ventricle; in simpler terms, it is the pressure against the ejection of the LV. In patients with normal LV function, the increased intrathoracic pressure during MV reduces venous return and preload, which reduces cardiac output. Alternatively, cardiac output can increase due to a concomitant reduction in the afterload.34 The influence of PEEP on the LV is complex. The PEEP improves arterial oxygenation and diminishes the intrapulmonary shunt, but PEEP also increases intrathoracic pressure. Therefore, the pressure difference between the LV and the systemic circulation is increased. Thus, with a constant blood pressure, less force is necessary for blood ejection from the LV.35 Interestingly, this effect is observed more often in patients sensitive to afterload changes than in patients with congestive heart failure. Conversely, during weaning from MV, when the patient starts breathing spontaneously, the negative intrathoracic pressure produces an increase in the LV afterload, and the previous increase in the LV ejection volume is lost. Normally, cardiac output increases in response to an increase in metabolic demand. Without this response, an increase in metabolic oxygen consumption can cause a reduction in the mixed venous oxygen saturation.36 This, in some patients, can provoke myocardial ischemia and cause weaning failure. 1.2. Extracorporeal circulation (ECC) The vascular contribution to the lungs depends almost exclusively on the pulmonary arteries. The principal function of the bronchial circulation is to feed the pulmonary structures; thus, it is responsible for approximately 1% of the pulmonary circulation. However, when the arterial circulation is chronically compromised, the bronchial circulation takes on a leading role. It was previously thought that when patients were submitted to ECC (on-pump surgery) without pulmonary perfusion, a “perfect” model of pulmonary ischemia would be produced. Indeed, compared to on-pump, off-pump surgery was associated with a reduced inflammatory response (cytokines) and lower levels of circulating neutrophils and monocytes.37 Other studies in procedures without ECC have found lower pulmonary complication rates, earlier extubations, shorter MV durations, and a lower incidence of pneumonia compared to those with ECC.38
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However, other studies have shown that off-pump surgery was not always more beneficial than on-pump surgery. Groeneveld et al38 studied PPD after cardiac surgery with and without ECC. They observed that ECC did not contribute to the development of lung dysfunction and did not influence the incidence of respiratory or hemodynamic complications. Although the design of the study was limited, the results suggested that ECC was not a determinant for the development of PPD. 1.3. Systemic temperature Central temperature did not appear to significantly influence gas exchange (alveolar arterial difference in oxygen partial pressure, or PA-a O2) after an aorto-coronary bypass graft.39 Nevertheless, patients with normothermia exhibited decreases in the shunt fraction, PA-a O2, and the alveolus-arterial gradient of CO2. This suggested that normothermia might preserve pulmonary function after cardiopulmonary bypass surgery.40 2. Therapeutic measures that minimize PPD after cardiac surgery 2.1. Protective ventilation strategy-open lung approach (OLA) The OLA is a ventilatory strategy, initially used to treat patients with ARDS, that aims to reduce the shear forces generated by repetitive closing and opening of the alveoli in pulmonary areas with atelectasis. That is to say, OLA can prevent atelectasis and maintain open alveoli. This strategy must be applied with concomitant recruiting maneuvers and sufficient PEEP to counterbalance elastic recoil forces and ventilation must be achieved with minimum delta pressure (Pplateau-PEEP) to prevent pulmonary overdistension.41 The low delta pressure is typically achieved by using low tidal volumes (4e6 ml/kg). With this ventilatory strategy, sudden changes of volume in large alveolar zones are minimized.42 In fact, atelectases were not observed in CT-scans in healthy anesthetized children when the OLA strategy was used. Also, this OLA strategy reduces the loss of proteins in the alveoli by attenuating the alteration in surfactant.43 Furthermore, the prevention of atelectasis attenuates the shear forces and limits the perpetration of a vicious circle.44 With this strategy, the stress to the alveolocapillary membrane can be limited by preventing collapse at end-expiration. This was demonstrated by a decrease in the biochemical markers (purines) released by cells damaged after ventilation with high pressures.45 These effects were corroborated by van Kaam et al.,46 who showed in surfactant-depleted piglets that, after application of the OLA ventilatory strategy the inflammatory response was diminished considerably (IL-8 in BAL) compared to animals ventilated with low PEEP. It is important to stress that applying an adequate PEEP level and preventing the collapse at end-expiration minimizes the inflammatory response and diminishes bacterial translocation.47 The potential advantages of an OLA strategy are diverse. Miranda et al29 showed that OLA ventilation (tidal volume 6 ml/kg, PEEP 14 cm H2O), applied immediately after intubation, significantly diminished the levels of IL-8 and IL-10 compared to conventional ventilation (tidal volume 8 ml/kg, PEEP 5 cm H2O). During mechanical ventilation, the application of OLA was accompanied by significant increases in the PaO2/FiO2, suggesting a significant reduction in atelectasis.33 The same investigators later found48 that the effect of OLA on pulmonary volume was maintained after extubation; the day after extubation, the group ventilated with OLA showed 40% higher FRC than those given conventional ventilation. This effect on the FRC was maintained until the 5th day after extubation. Also, the OLA group had a significant decrease in the
incidence of hypoxemia (SpO2 < 90% with ambient air) on the day after extubation compared to the group with conventional ventilation. The OLA strategy has not been evaluated clinically in terms of outcomes (mortality or readmissions to the ICU). Nevertheless, as mentioned above, Chung et al.8 studied the causes for readmission into the ICU after cardiac surgery and found that, after discharge from the ICU, the percent increase in the required fraction of inspired oxygen was correlated to an increased risk of readmission. Taken together, these results suggested that the OLA strategy, which reduces the incidence of hypoxemia and increases FRC on discharge, might reduce the incidence of ICU readmission. Adverse effects of the OLA ventilatory strategy have also been reported. High PEEP levels increased the RV afterload, but did not affect contractility.49,50 In the previously described article,33 the authors showed that OLA ventilation did not affect pulmonary vascular resistance or the RV ejection fraction, as assessed with a pulmonary artery catheter in the patients that underwent cardiac surgery. These results confirmed those of Dyhr et al.,51 who found that cardiac output was not affected by high PEEP levels after a recruitment maneuver in cardiac surgery patients. During the OLA ventilation, high PEEP levels probably did not affect RV afterload because atelectasis was avoided and low tidal volumes were used. Duggan et al52 showed in healthy rats that atelectasis caused a significant increase in RV afterload; when untreated, this could develop into right cardiac failure. The effect of atelectasis on the RV afterload can be explained by two mechanisms. First, local hypoxic pulmonary vasoconstriction is induced in nonaerated lung areas.53 Second, capillary compression occurs due to the overdistension in aerated lung areas. Several studies have investigated the effects of OLA strategy and isolated recruitment maneuvers on RV afterload. The patients included in those studies underwent cardiac surgery without a history of RV failure.54,55 Clinical and experimental studies suggested that, after achieving an outlying recruitment maneuver, RV afterload increased after 1 or 2 min. Thus, this was considered a transitory adverse effect that could occur in patients with no previous history of right cardiac failure. Another study clearly showed that high PEEP levels during ventilation, in accordance with OLA, did not decrease the RV preload when the patients had an adequate previous preload.33 Nevertheless, it is necessary to be cautious with these isolated recruitment maneuvers in patients with previous right cardiac failure; in our group, we perform them with exhaustive monitoring and abort them when adverse events are imminent, according to the monitored values. Finally, another potential adverse effect of OLA is a possible increase in the incidence of pneumothorax. Recruitment maneuvers that require high inspiratory pressures during a short period of time pose the potential risk of barotrauma. The results have been discrepant in previous studies on patients with ARDS. Some showed that OLA was associated with an increasing incidence of pneumothorax,56 and others did not find any differences between patients treated with OLA and those treated with the conventional ventilatory strategy.57,48 Miranda et al. found that a high inspiratory pressure (50 cm H2O) applied for only a few seconds did not contribute to an increase of pneumothorax in patients that underwent cardiac surgery. Based on the above results, our group supports an OLA strategy that is initiated after intubating the patient in the operating room and continued up to the extubation of the patient. As mentioned previously, there are great potential advantages of the OLA strategy (reducing ventilator-induced pulmonary inflammation, increasing the PaO2/FiO2, attenuating the postoperative reduction in FRC, decreasing the incidence of hypoxemia), and we have not
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found adverse effects in this context (no increase in RV afterload, no increase in the incidence of pneumothorax, no effect on preload, etc.). 2.2. Ventilation during ECC Hypoventilation during ECC is associated with the development of micro-atelectasis, hydrostatic pulmonary edema, poor compliance, and an increased incidence of infection.58 Hence, it is hypothesized that maintaining mechanical ventilation during ECC may limit postoperative pulmonary complications.59 Atelectasis is the principal determinant in postoperative lung gas exchange and may play a larger role in ventilatory abnormalities after cardiac surgery than edema due to increased permeability. Loeckinger et al.59 studied continuous positive airway pressure (CPAP) at 10 cm H2O during ECC and the effect on postoperative pulmonary gas exchange. They found a significantly higher PaO2, a significantly lower PA-a O2 4 h after ECC, and better gas exchange after extubation in the CPAP group compared to controls. A posteriori, John et al.,60 demonstrated that maintaining ventilation with a tidal volume of 5 ml/kg during ECC provided other benefits compared to discontinued ventilation. He found a decrease in extravascular lung water and a shorter extubation time in the ventilation group compared to controls. Continued ventilation during ECC was suggested to be an easy method to carry out, and it incurred no additional cost. Very recently, Imura et al.61 designed a highly attractive study in an experimental model of pigs. Eighteen Yorkshire pigs were subjected to 120 min of cardiopulmonary bypass. Six animals served as controls with an endotracheal tube open to the atmosphere during a cardiopulmonary bypass. The remaining animals were divided into 2 groups of 6: one group received CPAP of 5 cm H2O, and the other group received low frequency ventilation (5 breaths/min). The hemodynamic parameters were similar in all three groups. After ECC, the low frequency ventilation group showed significantly better oxygen tension and alveolar arterial oxygen gradient, higher levels of adenine nucleotide, lower levels of lactate dehydrogenase (LDH), reduced histologic damage in a lung biopsy, and lower DNA levels in BAL compared to the control group. The CPAP group showed only significantly reduced LDH levels compared to controls. These striking results prompted other investigators to write comments in letters to the editor.62 Apparently, the low frequency ventilation approach (5 breaths per min during ECC) is easy, safe, low-cost, and potentially quite beneficial. 3. Conclusions The incidence of PPD after cardiac surgery remains unacceptably high. The mechanisms involved in its development include two fundamental causes: the trauma of the surgical procedure and the insult of mechanical ventilation of the lung in an inflammatory environment. Pulmonary inflammation is aggravated by suboptimal mechanical ventilation of the lung. Our group recommends initiating an OLA strategy early in the procedure (after the orotracheal intubation) with low tidal volumes (tidal volume 6 ml/kg, PEEP 8e14 cm H2O) and recruitment maneuvers. During ECC, low frequency ventilation appears to be a highly promising approach. With the combination of these two ventilatory strategies, we can expect considerable progress in gas exchange parameters, minor elevations in inflammatory mediators, better postoperative FRC, and reduced incidence of readmission into the ICU. Finally, in our opinion, this can all be accomplished without any adverse hemodynamic effects. Conflict of interest None.
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bacteremia after experimental Klebsiella pneumoniae inoculation. Intensive Care Med 1998;24:172e7. Reis Miranda D, Struijs A, Koetsier P, van Thiel R, Schepp R, Hop W, et al. Open lung ventilation improves functional residual capacity after extubation in cardiac surgery. Crit Care Med 2005;33:2253e8. Schmitt JM, Vieillard-Baron A, Augarde R, Prin S, Page B, Jardin F. Positive endexpiratory pressure titration in acute respiratory distress syndrome patients: impact on right ventricular outflow impedance evaluated by pulmonary artery Doppler flow velocity measurements. Crit Care Med 2001;29:1154e8. Berglund JE, Haldén E, Jakobson S, Landelius J. Echocardiographic analysis of cardiac function during high PEEP ventilation. Intensive Care Med 1994;20:174e80. Dyhr T, Laursen N, Larsson A. Effects of lung recruitment maneuver and positive end-expiratory pressure on lung volume, respiratory mechanics and alveolar gas mixing in patients ventilated after cardiac surgery. Acta Anaesthesiol Scand 2002;46:717e25. Duggan M, McCaul CL, McNamara PJ, Engelberts D, Ackerley C, Kavanagh BP. Atelectasis causes vascular leak and lethal right ventricular failure in uninjured rat lungs. Am J Respir Crit Care Med 2003;167:1633e40. Pirlo AF, Benumof JL, Trousdale FR. Atelectatic lobe blood flow: open vs. closed chest, positive pressure vs. spontaneous ventilation. J Appl Physiol 1981;50:1022e6. Nielsen J, Ostergaard M, Kjaergaard J, Tingleff J, Berthelsen PG, Nygard E, et al. Lung recruitment maneuver depresses central hemodynamics in patients following cardiac surgery. Intensive Care Med 2005;31:1189e94. Lim SC, Adams AB, Simonson DA, Dries DJ, Broccard AF, Hotchkiss JR, et al. Transient hemodynamic effects of recruitment maneuvers in three experimental models of acute lung injury. Crit Care Med 2004;32:2378e84. Eisner MD, Thompson BT, Schoenfeld D, Anzueto A, Matthay MA. Airway pressures and early barotrauma in patients with acute lung injury and acute respiratory distress syndrome. Am J Respir Crit Care Med 2002;165:978e82. Weg JG, Anzueto A, Balk RA, Wiedemann HP, Pattishall EN, Schork MA, et al. The relation of pneumothorax and other air leaks to mortality in the acute respiratory distress syndrome. N Engl J Med 1998;338:341e6. Magnusson L, Zemgulis V, Tenling A, Wernlund J, Tydén H, Thelin S, et al. Use of a vital capacity maneuver to prevent atelectasis after cardiopulmonary bypass: an experimental study. Anesthesiology 1998;88:134e42. Loeckinger A, Kleinsasser A, Lindner KH, Margreiter J, Keller C, Hoermann C. Continuous positive airway pressure at 10 cm H(2)O during cardiopulmonary bypass improves postoperative gas exchange. Anesth Analg 2000;91:522e7. John LC, Ervine IM. A study assessing the potential benefit of continued ventilation during cardiopulmonary bypass. Interact Cardiovasc Thorac Surg 2008;7:14e7. Imura H, Caputo M, Lim K, Ochi M, Suleiman MS, Shimizu K, et al. Pulmonary injury after cardiopulmonary bypass: beneficial effects of low-frequency mechanical ventilation. J Thorac Cardiovasc Surg 2009;137:1530e7. Letters to the. J Thorac Cardiovasc Surg 2010;139:234e6. author reply 2367.
Contents lists available at ScienceDirect
Current Anaesthesia & Critical Care journal homepage: www.elsevier.com/locate/cacc
FOCUS ON: MECHANICAL VENTILATION IN THE OR
Mechanical ventilation in cardiac surgery Rafael Badenes*, F. Javier Belda, Gerardo Aguilar Department Anesthesiology and Critical Care, Hospital Clinic Universitari, Valencia, Spain
s u m m a r y Keywords: Postoperative pulmonary dysfunction Mechanical ventilation Open lung approach Cardiac surgery
Postoperative pulmonary dysfunction (PPD) is a frequent complication after cardiac surgery. Its pathogenesis is related to pulmonary inflammation, but this appears to be secondary to multiple etiological factors, including the surgical procedure itself, extra corporeal circulation (ECC), ischemia-reperfusion injury, and mechanical ventilation (MV). On the other hand, the presence of atelectasis remains one of the principal causes of PPD. The open lung approach (OLA) is a protective ventilation strategy, typically initiated after orotracheal intubation and maintained until extubation of the patient. Compared to a conventional ventilation strategy, OLA improves gas exchange parameters, induces a minor elevation of inflammatory mediators, and retains more residual functional capacity. Finally, recent studies have shown that the addition of low frequency ventilation during ECC can decrease the incidence of PPD after cardiac surgery. Ó 2010 Elsevier Ltd. All rights reserved.
1. Introduction Postoperative pulmonary dysfunction (PPD) is a common complication after cardiac surgery,1 but it is not clear what mechanisms are involved in its development. Therefore, it is unknown which therapeutic maneuvers might reduce the incidence of PPD. The manifestations of PPD include a frequent presence of pleural effusion (27e95%)2 and atelectasis (16.6e88%),3 detectable postoperative hypoxemia without clinical symptoms (3e10%),4 and the development of acute respiratory distress syndrome (ARDS). The incidence of ARDS is low (0.5e1.7%),5 but it is associated with high mortality (50e90%).6 40% of patients readmitted into intensive care units (ICU) present with respiratory failure.7 Chung et al8 found that, after cardiac surgery, a high inspiratory oxygen requirement during the ICU stay was related to increasing risk of readmission (odds ratio 1.09, p < 0.05). In addition, after cardiac surgery, the systemic inflammatory response was typically associated with a moderate pulmonary component, characterized by reduced pulmonary compliance, pulmonary edema, an increased intrapulmonary shunt fraction, and reduced functional residual capacity (FRC).9
* Corresponding author. GV Fernando el Católico 5-5, 46008, Valencia, Spain. Tel.: þ34696819532. E-mail address: [email protected] (R. Badenes). 0953-7112/$ e see front matter Ó 2010 Elsevier Ltd. All rights reserved. doi:10.1016/j.cacc.2010.07.006
1.1. Mechanisms involved in the development of PPD after cardiac surgery 1.1.1. Mechanical ventilation (MV) with general anesthesia After cardiac surgery, the FRC typically diminishes by 40e50% during the first hours after extubation10; in contrast to other types of surgery where FRC is reduced by about 20% after extubation.11 The exaggerated effect observed after cardiac surgery remains unexplained, but seems to be related to pulmonary inflammation. Many etiological factors play an important role in this effect, including extra corporeal circulation (ECC), injuries due to ischemia-reperfusion, the surgical intervention, and MV. The presence of atelectasis is one of the principal causes of PPD,12 and there is a correlation between the amount of atelectasis and the intrapulmonary shunt.13 Pulmonary inflammation induced by MV is the result of combined mechanical and biological trauma. Mechanical trauma refers to the stress related to alveolar overdistension due to large tidal volumes (volutrauma) or pressures (barotrauma). This stress causes epithelial injury, loss of epithelial integrity, and edema. In particular, stress is produced in the presence of large areas of atelectasis, when tidal volume inflates fewer areas of alveoli. Biological trauma occurs upon ventilating normal lungs with high inspiratory volumes, which triggers local and systemic inflammatory responses. Consequently, the release of cytokines from a variety of lung cells alters cellular pathways that are important for normal function of tissues and organs; this effect has been called biotrauma.
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The development of atelectasis is closely related to the loss of surfactant and to repetitive closing and re-opening of the alveoli. Atelectasis is a primary factor in the development of pulmonary inflammation.14 When dependent parts of the lung are atelectatic when the lung is exposed to high ventilating pressures, the traction forces applied to junctional tissues can be very high; for example, the traction force can approximate 140 cm H2O with an alveolar pressure of 30 cm H2O.15 This “stress induced failure” of the alveolar capillary membrane is responsible for increased microvascular permeability, edema, and an influx of plasmatic proteins, which16,17 inactivate the surfactant. Dreyfuss et al. demonstrated that the determining factor for pulmonary injury and inflammation was ventilation with high tidal volumes (producing high transpulmonary pressure), but not ventilation with high pressures (producing low transpulmonary pressure). Biotrauma results from the mechanical, or “shear” forces between the open and closed alveoli and overdistension of alveoli, which provoke inflammatory responses at the pulmonary level. However, it is not clear how mechanical forces are translated into the biochemical signals that produce biotrauma. Theories proposed have implied mechanoreceptors, stretch-sensitive channels, activation of the inflammatory cascade,14 and activation of the transcription of the nuclear factor kappa.18 Many experimental studies have studied the relationship of mechanical distension of the alveolocapillary membrane and the production of mediators. 19e25 During MV, pulmonary endothelial cells are exposed to stress, particularly during repetitive opening and closing of alveoli in atelectatic regions, but also during changes in transluminal pressure with alveolar inflation. Mechanical stress in the alveolocapillary membrane can affect the structural proteins of the membrane, the ion channels, and the cellular cytoskeleton; subsequent changes in cellular signaling cascades can produce diverse effects, including liberation of cytokines and other mediators, activation of transcription factors, altered expression of genes and proteins, cellular division, or even cellular death.26 The exaggerated inflammatory response (production of interleukins, inflammatory mediators, etc) is not limited to the pulmonary tissues, but may cross into the systemic circulation27 and cause a systemic inflammatory response. Ranieri et al.28 confirmed previous experimental findings in patients with ARDS. The levels of tumor necrosis factor-alpha (TNFalpha), interleukin-6 (IL-6), and IL-8 in bronchoalveolar lavage (BAL) were lower with a ventilatory strategy titrated for optimal positive end-expiratory pressure (PEEP) and low tidal volumes than with a strategy that used high tidal volumes. In a multicentre study with 861 patients, ventilation with low tidal volumes (6 ml/kg) diminished plasma concentrations of IL-6 and significantly reduced the 28-day mortality of patients with ARDS. This suggested that the application of suitable ventilatory strategies clearly affected the development of an inflammatory response after cardiac surgery. Miranda et al.29 found that an open lung strategy (tidal volume, 6 ml/kg; PEEP, 14 cm H2O) applied immediately after intubation in cardiac surgery reduced the plasma levels of IL-6, IL-8, IL-10, TNFalpha, and interferon-gamma. Thus, the exaggerated pulmonary dysfunction after cardiac surgery was apparently due to two different types of stress. One was induced by MV (mechanical stress and biotrauma) and the second was the inflammatory response to the cardiac surgery. Other factors that contribute to the development of PPD after cardiac surgery include a ventilatory strategy that permits atelectasis and the setting of high volumes and low PEEP levels.30 1.1.2. Cardiovascular effects of MV It is well known that MV can have potentially adverse cardiovascular effects, depending on the ventilatory strategy. Patients with cardiovascular pathology exhibit a hemodynamic response to
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MV that depends on numerous factors, including myocardial function, the state of intravascular volume, intrathoracic pressure, pulmonary distention, intrinsic autonomic tone, etc. Moreover, many patients present with pump failure and/or valvular pathology (fundamental indications for the cardiac surgery). The MV per se, may produce changes in the right ventricle (RV) preload and afterload. Due to an increase in intrathoracic pressure, the gradient between the right atrium and the venous system may be reduced, diminishing the preload, and thus, the cardiac output of the RV. A reduction in lung volume at the end of expiration and alveolar collapse stimulate pulmonary hypoxic vasoconstriction (PHV), which diverts blood flow to areas that are better aerated.31 When alveolar collapse is prevented with PEEP, recruiting maneuvers and a protective ventilatory strategy can reduce the vascular pulmonary resistance and prevent PHV.32,33 Miranda et al. studied the effects of an open lung strategy on the RV afterload after cardiac surgery. The patients were randomized into two groups, one with the open lung strategy (high levels of PEEP, tidal volumes of 4e6 ml/kg, and frequent recruitment maneuvers) and the other with conventional MV (PEEP 5 cm H2O and tidal volumes of 6e8 ml/kg) after the surgery. No increases were observed in the RV afterload. In addition, the protective strategy group showed an improvement in the ratio of partial pressure of arterial oxygen to the fraction of inspired oxygen (PaO2/FiO2). Left ventricle (LV) afterload is defined as the end-systolic volume or as the maximum tension in the wall of the left ventricle; in simpler terms, it is the pressure against the ejection of the LV. In patients with normal LV function, the increased intrathoracic pressure during MV reduces venous return and preload, which reduces cardiac output. Alternatively, cardiac output can increase due to a concomitant reduction in the afterload.34 The influence of PEEP on the LV is complex. The PEEP improves arterial oxygenation and diminishes the intrapulmonary shunt, but PEEP also increases intrathoracic pressure. Therefore, the pressure difference between the LV and the systemic circulation is increased. Thus, with a constant blood pressure, less force is necessary for blood ejection from the LV.35 Interestingly, this effect is observed more often in patients sensitive to afterload changes than in patients with congestive heart failure. Conversely, during weaning from MV, when the patient starts breathing spontaneously, the negative intrathoracic pressure produces an increase in the LV afterload, and the previous increase in the LV ejection volume is lost. Normally, cardiac output increases in response to an increase in metabolic demand. Without this response, an increase in metabolic oxygen consumption can cause a reduction in the mixed venous oxygen saturation.36 This, in some patients, can provoke myocardial ischemia and cause weaning failure. 1.2. Extracorporeal circulation (ECC) The vascular contribution to the lungs depends almost exclusively on the pulmonary arteries. The principal function of the bronchial circulation is to feed the pulmonary structures; thus, it is responsible for approximately 1% of the pulmonary circulation. However, when the arterial circulation is chronically compromised, the bronchial circulation takes on a leading role. It was previously thought that when patients were submitted to ECC (on-pump surgery) without pulmonary perfusion, a “perfect” model of pulmonary ischemia would be produced. Indeed, compared to on-pump, off-pump surgery was associated with a reduced inflammatory response (cytokines) and lower levels of circulating neutrophils and monocytes.37 Other studies in procedures without ECC have found lower pulmonary complication rates, earlier extubations, shorter MV durations, and a lower incidence of pneumonia compared to those with ECC.38
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However, other studies have shown that off-pump surgery was not always more beneficial than on-pump surgery. Groeneveld et al38 studied PPD after cardiac surgery with and without ECC. They observed that ECC did not contribute to the development of lung dysfunction and did not influence the incidence of respiratory or hemodynamic complications. Although the design of the study was limited, the results suggested that ECC was not a determinant for the development of PPD. 1.3. Systemic temperature Central temperature did not appear to significantly influence gas exchange (alveolar arterial difference in oxygen partial pressure, or PA-a O2) after an aorto-coronary bypass graft.39 Nevertheless, patients with normothermia exhibited decreases in the shunt fraction, PA-a O2, and the alveolus-arterial gradient of CO2. This suggested that normothermia might preserve pulmonary function after cardiopulmonary bypass surgery.40 2. Therapeutic measures that minimize PPD after cardiac surgery 2.1. Protective ventilation strategy-open lung approach (OLA) The OLA is a ventilatory strategy, initially used to treat patients with ARDS, that aims to reduce the shear forces generated by repetitive closing and opening of the alveoli in pulmonary areas with atelectasis. That is to say, OLA can prevent atelectasis and maintain open alveoli. This strategy must be applied with concomitant recruiting maneuvers and sufficient PEEP to counterbalance elastic recoil forces and ventilation must be achieved with minimum delta pressure (Pplateau-PEEP) to prevent pulmonary overdistension.41 The low delta pressure is typically achieved by using low tidal volumes (4e6 ml/kg). With this ventilatory strategy, sudden changes of volume in large alveolar zones are minimized.42 In fact, atelectases were not observed in CT-scans in healthy anesthetized children when the OLA strategy was used. Also, this OLA strategy reduces the loss of proteins in the alveoli by attenuating the alteration in surfactant.43 Furthermore, the prevention of atelectasis attenuates the shear forces and limits the perpetration of a vicious circle.44 With this strategy, the stress to the alveolocapillary membrane can be limited by preventing collapse at end-expiration. This was demonstrated by a decrease in the biochemical markers (purines) released by cells damaged after ventilation with high pressures.45 These effects were corroborated by van Kaam et al.,46 who showed in surfactant-depleted piglets that, after application of the OLA ventilatory strategy the inflammatory response was diminished considerably (IL-8 in BAL) compared to animals ventilated with low PEEP. It is important to stress that applying an adequate PEEP level and preventing the collapse at end-expiration minimizes the inflammatory response and diminishes bacterial translocation.47 The potential advantages of an OLA strategy are diverse. Miranda et al29 showed that OLA ventilation (tidal volume 6 ml/kg, PEEP 14 cm H2O), applied immediately after intubation, significantly diminished the levels of IL-8 and IL-10 compared to conventional ventilation (tidal volume 8 ml/kg, PEEP 5 cm H2O). During mechanical ventilation, the application of OLA was accompanied by significant increases in the PaO2/FiO2, suggesting a significant reduction in atelectasis.33 The same investigators later found48 that the effect of OLA on pulmonary volume was maintained after extubation; the day after extubation, the group ventilated with OLA showed 40% higher FRC than those given conventional ventilation. This effect on the FRC was maintained until the 5th day after extubation. Also, the OLA group had a significant decrease in the
incidence of hypoxemia (SpO2 < 90% with ambient air) on the day after extubation compared to the group with conventional ventilation. The OLA strategy has not been evaluated clinically in terms of outcomes (mortality or readmissions to the ICU). Nevertheless, as mentioned above, Chung et al.8 studied the causes for readmission into the ICU after cardiac surgery and found that, after discharge from the ICU, the percent increase in the required fraction of inspired oxygen was correlated to an increased risk of readmission. Taken together, these results suggested that the OLA strategy, which reduces the incidence of hypoxemia and increases FRC on discharge, might reduce the incidence of ICU readmission. Adverse effects of the OLA ventilatory strategy have also been reported. High PEEP levels increased the RV afterload, but did not affect contractility.49,50 In the previously described article,33 the authors showed that OLA ventilation did not affect pulmonary vascular resistance or the RV ejection fraction, as assessed with a pulmonary artery catheter in the patients that underwent cardiac surgery. These results confirmed those of Dyhr et al.,51 who found that cardiac output was not affected by high PEEP levels after a recruitment maneuver in cardiac surgery patients. During the OLA ventilation, high PEEP levels probably did not affect RV afterload because atelectasis was avoided and low tidal volumes were used. Duggan et al52 showed in healthy rats that atelectasis caused a significant increase in RV afterload; when untreated, this could develop into right cardiac failure. The effect of atelectasis on the RV afterload can be explained by two mechanisms. First, local hypoxic pulmonary vasoconstriction is induced in nonaerated lung areas.53 Second, capillary compression occurs due to the overdistension in aerated lung areas. Several studies have investigated the effects of OLA strategy and isolated recruitment maneuvers on RV afterload. The patients included in those studies underwent cardiac surgery without a history of RV failure.54,55 Clinical and experimental studies suggested that, after achieving an outlying recruitment maneuver, RV afterload increased after 1 or 2 min. Thus, this was considered a transitory adverse effect that could occur in patients with no previous history of right cardiac failure. Another study clearly showed that high PEEP levels during ventilation, in accordance with OLA, did not decrease the RV preload when the patients had an adequate previous preload.33 Nevertheless, it is necessary to be cautious with these isolated recruitment maneuvers in patients with previous right cardiac failure; in our group, we perform them with exhaustive monitoring and abort them when adverse events are imminent, according to the monitored values. Finally, another potential adverse effect of OLA is a possible increase in the incidence of pneumothorax. Recruitment maneuvers that require high inspiratory pressures during a short period of time pose the potential risk of barotrauma. The results have been discrepant in previous studies on patients with ARDS. Some showed that OLA was associated with an increasing incidence of pneumothorax,56 and others did not find any differences between patients treated with OLA and those treated with the conventional ventilatory strategy.57,48 Miranda et al. found that a high inspiratory pressure (50 cm H2O) applied for only a few seconds did not contribute to an increase of pneumothorax in patients that underwent cardiac surgery. Based on the above results, our group supports an OLA strategy that is initiated after intubating the patient in the operating room and continued up to the extubation of the patient. As mentioned previously, there are great potential advantages of the OLA strategy (reducing ventilator-induced pulmonary inflammation, increasing the PaO2/FiO2, attenuating the postoperative reduction in FRC, decreasing the incidence of hypoxemia), and we have not
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found adverse effects in this context (no increase in RV afterload, no increase in the incidence of pneumothorax, no effect on preload, etc.). 2.2. Ventilation during ECC Hypoventilation during ECC is associated with the development of micro-atelectasis, hydrostatic pulmonary edema, poor compliance, and an increased incidence of infection.58 Hence, it is hypothesized that maintaining mechanical ventilation during ECC may limit postoperative pulmonary complications.59 Atelectasis is the principal determinant in postoperative lung gas exchange and may play a larger role in ventilatory abnormalities after cardiac surgery than edema due to increased permeability. Loeckinger et al.59 studied continuous positive airway pressure (CPAP) at 10 cm H2O during ECC and the effect on postoperative pulmonary gas exchange. They found a significantly higher PaO2, a significantly lower PA-a O2 4 h after ECC, and better gas exchange after extubation in the CPAP group compared to controls. A posteriori, John et al.,60 demonstrated that maintaining ventilation with a tidal volume of 5 ml/kg during ECC provided other benefits compared to discontinued ventilation. He found a decrease in extravascular lung water and a shorter extubation time in the ventilation group compared to controls. Continued ventilation during ECC was suggested to be an easy method to carry out, and it incurred no additional cost. Very recently, Imura et al.61 designed a highly attractive study in an experimental model of pigs. Eighteen Yorkshire pigs were subjected to 120 min of cardiopulmonary bypass. Six animals served as controls with an endotracheal tube open to the atmosphere during a cardiopulmonary bypass. The remaining animals were divided into 2 groups of 6: one group received CPAP of 5 cm H2O, and the other group received low frequency ventilation (5 breaths/min). The hemodynamic parameters were similar in all three groups. After ECC, the low frequency ventilation group showed significantly better oxygen tension and alveolar arterial oxygen gradient, higher levels of adenine nucleotide, lower levels of lactate dehydrogenase (LDH), reduced histologic damage in a lung biopsy, and lower DNA levels in BAL compared to the control group. The CPAP group showed only significantly reduced LDH levels compared to controls. These striking results prompted other investigators to write comments in letters to the editor.62 Apparently, the low frequency ventilation approach (5 breaths per min during ECC) is easy, safe, low-cost, and potentially quite beneficial. 3. Conclusions The incidence of PPD after cardiac surgery remains unacceptably high. The mechanisms involved in its development include two fundamental causes: the trauma of the surgical procedure and the insult of mechanical ventilation of the lung in an inflammatory environment. Pulmonary inflammation is aggravated by suboptimal mechanical ventilation of the lung. Our group recommends initiating an OLA strategy early in the procedure (after the orotracheal intubation) with low tidal volumes (tidal volume 6 ml/kg, PEEP 8e14 cm H2O) and recruitment maneuvers. During ECC, low frequency ventilation appears to be a highly promising approach. With the combination of these two ventilatory strategies, we can expect considerable progress in gas exchange parameters, minor elevations in inflammatory mediators, better postoperative FRC, and reduced incidence of readmission into the ICU. Finally, in our opinion, this can all be accomplished without any adverse hemodynamic effects. Conflict of interest None.
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