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  1. 1. reviews Pulmonary Dysfunction After Cardiac Surgery* Calvin S.H. Ng, MBBS (Hons); Song Wan, MD, PhD; Anthony P.C. Yim, MD, FCCP; and Ahmed A. Arifi, MD Postoperative lung injury is one of the most frequent complications of cardiac surgery that impacts significantly on health-care expenditures and largely has been believed to result from the use of cardiopulmonary bypass (CPB). However, recent comparative studies between conven- tional and off-pump coronary artery bypass grafting have indicated that CPB itself may not be the major contributor to the development of postoperative pulmonary dysfunction. In our study, we review the associated physiologic, biochemical, and histologic changes, with particular reference to the current understanding of underlying mechanisms. Intraoperative modifications aiming at limiting lung injury are discussed. The potential benefits of maintaining ventilation and pulmonary artery perfusion during CPB warrant further investigation. (CHEST 2002; 121:1269 –1277) Key words: cardiac surgery; cardiopulmonary bypass; cytokine; inflammatory response; ischemia-reperfusion; lung injury; neutrophils; ventilation Abbreviations: CABG coronary artery bypass grafting; CPAP continuous positive airway pressure; CPB cardiopulmonary bypass; IL interleukin; LT leukotriene; MMP matrix metalloproteinase; NO nitric oxide; PA pulmonary artery; P(A-a)O2 alveolar-arterial oxygen pressure difference; PMN polymorphonuclear cell; TNF tumor necrosis factor; TXB2 thromboxane B2; VCM vital capacity maneuverP ostoperative cardiopulmonary bypass (CPB) is a undergoing pulmonary dysfunction in patients behind the complex pathophysiology of CPB- induced lung injury remains incomplete. We reviewsignificant clinical problem and has long been rec- the current knowledge on this subject, with particu-ognized by cardiac surgeons, anesthetists, and inten- lar emphasis on some therapeutic modifications.sive-care physicians. The disturbance may be mani-fested as conditions ranging from subclinicalfunctional changes in most patients to full-blown The PhenomenonARDS in 2% of cases after CPB.1–3 The mortality Lung injury after CPB is evident by the presencerate associated with ARDS is 50%,1,2 not including of postoperative pulmonary functional, physiologic,the morbidity leading to prolonged postoperative biochemical, and histologic changes.recoveries and hospital stays. Despite years of re-search into this phenomenon, the understanding Physiologic Changes*From the Division of Cardiothoracic Surgery, The Chinese The physiologic disturbance after CPB can beUniversity of Hong Kong, Prince of Wales Hospital, Hong Kong, categorized grossly into abnormal gas exchange andChina.This study was supported in part by the Direct Grant for poor lung mechanics. The assessment of these func-Research (Chinese University of Hong Kong No. CRE-2001– tions has been measured through numerous param-021) and the Research Grant Council Earmarked Grant (Chinese eters, such as the alveolar-arterial oxygen pressureUniversity of Hong Kong No. 4310/99M), Hong Kong SAR.Manuscript received March 20, 2001; revision accepted May 31, difference (P[A-a]O2), intrapulmonary shunt func-2001. tion, the degree of pulmonary edema (ie, extravas-Correspondence: Ahmed A. Arifi, MD, Division of Cardiotho- cular lung water), lung compliance, and pulmonaryracic Surgery, The Chinese University of Hong Kong, Prince ofWales Hospital, Sha Tin, NT Hong Kong; e-mail: Arifiahmed@ vascular resistance. Significantly increased P(A-a) and pulmonary shunt fraction, together with CHEST / 121 / 4 / APRIL, 2002 1269 Downloaded from at New York University Medical Center on September 1, 2006
  2. 2. creased functional residual capacity and carbon mon- creased 7S protein levels have been shown to beoxide transfer factor, have been observed in patients associated with high matrix metalloproteinaseafter CPB.4,5 Disturbances of lung mechanics in (MMP; proteolytic enzyme) and neutrophil concen-terms of poor static and dynamic lung compliance trations in the BAL fluid of patients after they haveafter CPB also were noted.6,7 In addition to these undergone CPB.19 In addition, the lung is also a richabnormalities, lung function tests after CPB in chil- source of procalcitonin. The plasma concentration ofdren and neonates have shown lower FVC levels, procalcitonin can increase dramatically during pul-inspiratory capacities, and small airway flow rates.8 monary inflammation.20 Compared with many other Lung disturbances after CPB include increased inflammatory markers, a better correlation betweenlung permeability9 –14 and pulmonary vascular resis- high procalcitonin levels and the post-CPB Murraytance,15 as well as lung surfactant changes. Pulmo- lung injury score has been observed.18nary epithelial-capillary endothelial permeability is Decreased levels of exhaled NO were detectedclosely related to the formation of pulmonary edema, after CPB, citing a reduction of exhaled NO as aalveolar protein accumulation, and the facilitation of possible marker of pulmonary injury.21,22 It wasinflammatory cell sequestration, all of which conse- proposed that the production of NO decreased afterquently affect lung function. The increase in pulmo- CPB because of transient pulmonary vascular endo-nary permeability after CPB has been shown by theincreased rate of transfer of Tc 99m-labeled dieth- thelial or lung epithelial injury.21 Pearl et al22 corre-ylenetriamine pentaacetate,9 the protein accumula- lated a reduced exhaled NO level to poor pulmonarytion index of radiolabeled transferrin,10,11 the sys- compliance, elevated P(A-a)O2 levels, and elevatedtemic/bronchoalveolar urea ratio,11 the IV 67Ga level airway resistance after CPB. However, the exhaled(transferring binder),12 and other similar indica- NO level was found to have a poor correlation withtors.13 As a result, the BAL sample protein content plasma nitrite levels, indicating that decreased ex-can increase by more than threefold to fourfold after haled NO levels were mainly due to bronchiala patient undergoes CPB.14 Finally, CPB could epithelial dysfunction rather than to pulmonary en-affect the pulmonary surfactant activity, particularly dothelial damage.22in infants and neonates.8,14 However, these changesappear to make no major contribution to the initial Histologic Changesstages of lung injury after CPB.10 Alveolar edema, extravasation of erythrocytes and neutrophils, and congested alveolar capillaries fol-Biochemical Changes lowing CPB also have been confirmed by testing of Various biochemical changes can reflect the pres- intraoperative lung biopsy specimens.23 On electronence of lung injury after CPB. These include the microscopy, pneumocytes and endothelial cells ap-substances directly or indirectly responsible for caus- peared swollen and necrotic. Similar lung structuraling lung injury (eg, neutrophil elastase), or the damage and changes after CPB also were observedproducts released from injured lung tissue (eg, 7S on electron microscopy in animal models.24protein fragment of collagen or procalcitonin), andthe reduction of products normally released by thelung (eg, nitric oxide [NO]). How Much of the Lung Injury Is CPB- Neutrophil elastase, a proteolytic enzyme, has long Related?been measured as a marker of pulmonary injury afterCPB both in the systemic circulation and in the BAL Few would argue about the presence of lungfluid. Tonz et al16 detected a positive correlation injury following CPB. However, pulmonary dysfunc-between systemic elastase peak concentrations and tion after CPB may be the result of multiple insultsboth the postoperative respiratory index and in- from various aspects of CPB surgery.25,26 Thesetrapulmonary shunt. However, the results of other include extra-CPB factors (ie, general anesthesia,studies have suggested that neutrophil elastase may sternotomy, and breach of the pleura) and intra-CPBnot be a consistent marker of lung injury since no factors (ie, blood contact with artificial material,correlation between elastase concentration and gas administration of heparin-protamine, hypothermia,exchange17 or acute lung injury score18 have been cardiopulmonary ischemia, and lung ventilatory ar-found. rest).26 Thus, it is questionable whether lung injury is The products associated with the breakdown of purely related to the use of CPB. To help answertype IV collagen (a main constituent of basement this, the degree of pulmonary dysfunction has beenmembrane), such as the 7S protein fragment of investigated clinically and experimentally under thecollagen, have been used to mark lung injury. In- following conditions.1270 Reviews Downloaded from at New York University Medical Center on September 1, 2006
  3. 3. Lung Dysfunction After Major Surgery and CPB of ventilatory support is concerned, the off-pump approach may be beneficial in high-risk patients It has been noticed that lung functional impair- undergoing repeat CABG,36 but not in those patientsment is inevitable after any major surgery, a condi- undergoing primary CABG.17,35,37 Therefore, al-tion that most likely is related to the general anes- though CPB is known to cause disturbances in lungthesia. Using CT scanning, researchers have found mechanics,6 CPB itself may not be a major contrib-that general anesthesia induces atelectasis in nearly utor to the postoperative gas exchange abnormali-all patients.27 However, CPB appears to cause addi- ties.35tional lung injury and to delay pulmonary recoverycompared with other types of major surgery,5 condi-tions that generally are believed to be due to thedamaging effects of a systemic inflammatory re- Current Understandingsponse associated with CPB.26 Yet, it is also notewor- PMN Activationthy that the continuing refinement of CPB materials(ie, the use of a membrane oxygenator instead of a It is well-known that CPB primes and activatesbubble oxygenator) as well as an improvement in polymorphonuclear cells (PMNs) through mechani-anesthetic management (ie, early extubation leading cal shear stress38,39 and contact with the artificialto fast-track recovery) have largely limited such an surfaces of the CPB circuit. Proinflammatory medi-additional lung injury.17 ators can subsequently promote lung injury by aug- menting PMN activation.26,40 For instance, several cytokines such as interleukin (IL)-1,41 IL-2,42 IL-6,Hypothermic vs Normothermic CPB IL-8,43 and tumor necrosis factor (TNF)- ,41,42 have The impact of temperature during CPB on lung been shown to promote PMN activation and recruit-function has been controversial. Birdi et al28 found ment. In addition, platelet-activating factor, leuke-that the perfusion temperature did not significantly mia inhibitory factor, and the arachidonic acid de-influence gas exchange (P[A-a]O2) after coronary rivative leukotriene (LT) B4 also can contribute toartery bypass grafting (CABG). However, reduced this process.44 Nevertheless, TNF- does not appearvalues for intrapulmonary shunt function, P(A-a)O2, to be responsible for causing neutrophil sequestra-and alveolar-arterial CO2 gradient were reported in tion.45 IL-6 also may play either an anti-inflamma-the normothermic group in another study,29 indicat- tory or a proinflammatory role in lung injury undering that normothermia may preserve lung function different conditions.46,47after CPB. Activated PMNs can further release a number of proteolytic enzymes and oxidative chemicals bothOn-Pump vs Off-Pump CABG into the systemic circulation and into local lung tissue. These substances include degrading MMPs,48 With the re-emergence of off-pump CABG, inter- PMN elastase,16 and oxygen-free radicals (ie, myelo-est has grown in the isolated effect of CPB on peroxidase, hydrogen peroxide, and superoxides).38postoperative pulmonary dysfunction. Off-pump These enzymes are instrumental in the developmentCABG was associated with reduced cytokine re- of post-CPB lung injury by breaking down thesponse when compared with on-pump CABG,30 –32 pulmonary ultrastructure, which results in increasedand the attenuated inflammatory reaction may lead pulmonary alveolar-endothelial permeability,to less impaired postoperative lung function. thereby affecting gas exchange and lung mechan- It has been shown that the number of circulating ics.16,24,49neutrophils and monocytes, as well as the level ofneutrophil elastase, were significantly lower follow- Neutrophil-Pulmonary Endothelial Adhesioning off-pump CABG compared to on-pumpCABG.32,33 Furthermore, oxidative stress, as indi- An increased expression of cell surface adhesioncated by the levels of lipid hydroperoxides and molecules (ie, CD1850 and CD11b51) following thenitrotyrosines, was also significantly lower in the activation of PMNs during CPB enhances neutro-off-pump CABG group.33 Kilger et al34 detected a phil-pulmonary endothelial adhesion.52 Subse-lower procalcitonin level, reflecting a reduced de- quently, it leads to further PMN activation and togree of lung injury, in patients undergoing off-pump local pulmonary neutrophil recruitment and seques-CABG. Despite these findings, both on-pump and tration, which may result in the release of neutrophiloff-pump CABG patients experienced similar de- proteolytic enzymes that cause direct lung damage.grees of decreased Pao2 and increased P(A-a)O2 , Intercellular adhesion molecule-1, a ligand ofand higher percentage of pulmonary shunt fractions CD18, has been seen to have increased expressionafter undergoing CABG.6,17,35 As far as the duration on pulmonary endothelial cells after CPB and CHEST / 121 / 4 / APRIL, 2002 1271 Downloaded from at New York University Medical Center on September 1, 2006
  4. 4. been associated with greater pulmonary neutrophil prostaglandin E2 concentrations and higher TXB2accumulation.53 Meanwhile, complement C3 also plasma concentrations, but LT-B4 and LT-C4 levelsplays an important role in inducing CD18 expres- remained unchanged.47 Hence, the imbalance be-sion,54 while C5a was particularly involved in the tween these arachidonic acid metabolites, ratherexpression of endothelial adhesion molecule P-selec- than their individual effects, may be more critical intin.55 In patients with a preexisting disease like the development of post-CPB pulmonary edema. Itdiabetes mellitus, a higher CD11b expression was has been suggested64 that increased pulmonary cy-noted after CPB when compared with nondiabetic clooxygenase-2 expression after CPB may contributepatients.56 This higher level of expression may in- to the development of such an imbalance.crease the risk of post-CPB complications.56Neutrophil Elastase Therapeutic Interventions or Peak systemic neutrophil elastase levels were ob- Modificationsserved at the end of CPB and have long been Pharmaceuticalsassociated with postoperative pulmonary injury. The commonly scrutinized pharmacologic agentsElastase is currently believed not only to be a marker with which to treat pulmonary dysfunction are cor-of PMN activation,48,57 but also to be responsible for ticosteroids and aprotinin. Corticosteroid adminis-causing direct injury by its proteolytic activity on tration before CPB has been shown to reduce thelung microvasculature and on endothelial cad- release of proinflammatory mediators such as IL-6,herins.58 Elastase release can be augmented by some IL-8, and TNF- ,26 although there was little effectother mediators such as IL-6.59 Meanwhile, elastase on complement activation.65– 67 In addition, methyl-also may serve as an activator of MMP-9.60 The prednisolone therapy can inhibit neutrophil CD11bantagonistic effect of MMP-9 on antiproteases (ie, expression51 and neutrophil complement-induced -1-protease inhibitor, which is an inhibitor of elas- chemotaxis,67 thereby decreasing neutrophil activa-tase activity) can lead to a positive-feedback relation- tion and post-CPB neutropenia.43 However, it failedship between elastase and MMP-9. to limit PMN elastase activity.65 In a porcine mod- el,68 post-CPB lung function (ie, P[A-a]O2, pulmo-Free Radicals nary vascular resistance, and extracellular fluid accu- Systemic48 and BAL fluid11 myeloperoxidase levels mulation) was better preserved after pretreatmenthave been reported to be highest at the end of CPB, with methylprednisolone. However, in a randomizedbut the contribution of myeloperoxidase to lung clinical trial, patients who received methylpred-injury is still controversial. It has been proposed61 nisolone during a sternotomy or at the onset of CPBthat increased free radical activity represents a po- had similar or higher postoperative P(A-a)O2 levelstential risk for ARDS after CPB. In fact, hyperoxic and pulmonary shunt function, as well as longerCPB is widely used in cardiac operations, and there intubation times compared with control subjects.7,69is concern about whether oxygenation may induce Furthermore, methylprednisolone therapy was un-oxygen-derived free radicals. It has been suggested able to prevent poor postoperative lung compli-that hyperoxic CPB, compared with normoxic CPB, ance.7,69increases oxygen free radical damage to the lung, as Aprotonin also has been shown to limit TNF-reflected by lower vital capacity and FEV1 levels.62 and neutrophil elastase release and to complement activation as well as neutrophil CD11b up-regulationArachidonic Acid Metabolites following CPB.26 IL-8 levels in the BAL fluid and pulmonary neutrophil sequestration after CPB was Many arachidonic acid metabolites have potent inhibited after the use of aprotinin.70 Aprotininvasoactive properties. Prostacyclin and prostaglandin priming of the CPB circuit may result in reducedE2 can cause pulmonary vasodilation, while LT-C4 postoperative morbidity and length of ICU stay.26and thromboxane B2 (TXB2) tend to cause vasocon- The inflammatory response, and pulmonary dysfunc-striction. The exact role of these mediators in pul- tion in particular, also was attenuated following themonary function after CPB is not entirely clear. use of aprotinin in patients undergoing heart trans-Interestingly, the lung was found to be a major plantation.26source of TXB2 following ischemia and reperfusion,and the correlation between raised TXB2 and im- Leukocyte Depletionpaired lung function has been shown in a sheep CPBmodel.63 Patients with more severe lung injury (Mur- Leukocyte depletion during CPB may limit theray lung injury score, grade 2) after CPB had lower postoperative inflammatory response, as measured1272 Reviews Downloaded from at New York University Medical Center on September 1, 2006
  5. 5. by reduced IL-8 production,71 although its beneficial gas diffusion by continuous ventilation is thereforeeffects on post-CPB pulmonary function have been worth measuring, since a certain degree of pulmo-inconsistent. In some studies,71,72 leukocyte deple- nary ischemia may exist during CPB when ventila-tion did not significantly improve postoperative Pao2 tion is stopped.levels and pulmonary hemodynamics. In other stud- The effects of ventilation during CPB have beenies, better preserved lung function73–76 and less free tested in a number of studies using vital capacityradical generation77 have been associated with maneuver (VCM; ie, a peak airway pressure of 40 cmleukocyte-depleted CPB. H2O with a fraction of inspired oxygen of 0.4 for about 15 s), continuous positive airway pressureModification of Artificial Circuit (CPAP), and continuous ventilation over the period of cardiac arrest. In a porcine model, VCM at the Heparin-coated circuits are associated with re- end of CPB resulted not only in improved gasduced activation of leukocytes and the release of exchange,86 but also reduced the incidence of atel-cytokines, resulting in less inflammatory reactions ectasis, as determined by a CT scan soon afterfollowing CPB.78 – 80 Compared with conventional CPB.85 However, repeating the VCM may not pro-circuits, heparin coating may improve lung compli- duce extra benefits.86 Meanwhile, better postopera-ance81 and pulmonary vascular resistance81 and may tive gas exchange and less pulmonary shunting werereduce intrapulmonary shunting.82 However, such observed in patients who received CPAP duringbenefits can be transient and may not be clinically CPB,87 although the beneficial effects of CPAP weresignificant.83 not evident in an animal CPB model.88 In addition, a comparison between the hollow To date, the evidence for the benefits of maintain-fiber and the flat sheet membrane oxygenators has ing ventilation alone during CPB is inconsistent, withsuggested that a greater pressure drop (which corre- most studies showing no significant preservation ofspond to shear stress) across the latter is associated lung function. Continuous ventilation during CPBwith a more pronounced activation of leukocytes was shown to provide no significant improvement induring clinical CPB and, therefore, should be pulmonary vascular resistance, cardiac index, or ox-avoided. ygen tensions in a pig model.89 Similarly, no differ- ences in pulmonary epithelial permeability wereContinuous Hemofiltration found between ventilated and nonventilated patients High-volume continuous hemofiltration, by poten- undergoing CPB.90 However, maintaining ventila-tially removing destructive and inflammatory sub- tion together with pulmonary artery (PA) perfusionstances from the circulation during CPB, can sig- during CPB may be advantageous. Friedman et al63nificantly reduce systemic edema, pulmonary compared total CPB (ie, no ventilation or PA perfu-hypertension, and improve lung function (eg, pulmo- sion) with partial CPB (ie, with ventilation and PAnary vascular resistance, lung dynamic compliance, perfusion) in a sheep model. They suggested thatand P[A-a]O2) after CPB.84 Continuous hemofiltra- ventilation with PA perfusion during CPB may havetion also may reduce lung tissue malondialdehyde a beneficial role in preserving lung function bylevels.84 limiting platelet and neutrophil sequestration and attenuating the TXB2 response after CPB.63 MoreMaintaining Mechanical Ventilation During CPB recently, it has been reported that liquid ventilation during CPB may increase oxygen delivery and may Cardiac surgeons have accepted the common decrease pulmonary vascular resistance when com-practice of stopping ventilation during CPB, as blood pared with air ventilation in a neonatal porcineoxygenation by the lungs is no longer required and model.91 Furthermore, liquid ventilation at a higherthe movement from mechanical ventilation may functional residual capacity was more effective ininterfere with the surgery. It is known that hypoven- optimizing postoperative alveolar distension andtilation during CPB is associated with the develop- lung volume.91ment of microatelectasis, hydrostatic pulmonaryedema, poor compliance, and a higher incidence of Maintaining Lung Perfusion During CPBinfection.85,86 Hence, some investigators63,85– 87 havehypothesized that mechanical ventilation during Since the early days of open heart surgery, it hasCPB may limit postoperative lung injury by prevent- been recognized that CPB is associated with pulmo-ing these complications. Moreover, the lungs are nary ischemic-reperfusion injury. However, as far astotally dependent on oxygen supply from the bron- preventing tissue ischemia during CPB is concerned,chial arteries in the period of cardiac arrest. The the lungs remain one of the least protected organs.additional contribution to lung tissue oxygenation via The lungs have a bimodal blood supply from the CHEST / 121 / 4 / APRIL, 2002 1273 Downloaded from at New York University Medical Center on September 1, 2006
  6. 6. and the bronchial arteries, with extensive anasto- proved lung compliance) compared with conven-motic connections. The bronchial arteries contribute tional heart-lung bypass, which may represent fur-about 1 to 3% of the total blood flow to the lungs ther supportive evidence for maintaining PAunder normal physiologic conditions. The relative perfusion during CPB.contribution of the bronchial arteries and PAs, and ofalveolar ventilation in delivering oxygen to maintainlung tissue viability is still unclear. The lungs are Summarypurely dependent on the bronchial arteries duringCPB to provide the 5% of whole-body oxygen uptake Although severe lung injury after CPB is uncom-that is necessary even under hypothermic condi- mon, it remains a significant cause of morbidity and mortality with a major impact on health-care expen-tion.92 However, from the experience of lung trans- ditures. There is little doubt that CPB is associatedplantation, it is known that the bronchial arteries can with pulmonary dysfunction, as supported by thebe sacrificed without causing any obvious pulmonary ample experimental and clinical evidence of chemi-dysfunction. In addition, ischemia and reperfusion cal, cellular, and pulmonary functional disturbancesduring CPB can enhance the regional release of after CPB. However, whether CPB itself is directlyinflammatory mediators, which may further induce responsible for postoperative lung dysfunction is stilllung injury. For instance, it has been demonstrat- controversial. Some studies have shown an attenu-ed93,94 that several proinflammatory cytokines, which ated inflammatory response following off-pumpare released from the heart during CPB, could be CABG, compared with on-pump CABG, with acleared in the lungs. Hence, it would be interesting similar degree of postoperative lung study whether maintaining PA perfusion during Our current research interests focus on ventilationCPB can attenuate the deterioration of lung function. and PA perfusion during clinical CPB. Some recent A number of therapeutic strategies for lung isch- encouraging results have shown that maintainingemia-reperfusion injury have been investigated. Im- lung ventilation and PA perfusion during CPB po-proved lung function was seen after CPB with PA tentially can minimize postoperative lung injury.perfusion compared with non-PA perfusion in ani- Further elucidation of the underlying mechanismmals,89,95 neonates,96 and adults,97 demonstrating the will help to refine therapeutic strategies for patientspotential beneficial role for maintaining PA perfu- who need cardiac surgery.sion during CPB. In animal models, CPB without PAperfusion resulted in significantly higher pulmonaryvascular resistance and P(A-a)O2 levels,89 with lower Referencespulmonary compliance.95 Liu and colleagues98 also 1 Fowler AA, Hamman RF, Good JT, et al. Adult respiratoryhave shown that the use of a hypothermic anti- distress syndrome: risk with common predispositions. Anninflammatory solution for PA perfusion may help to Intern Med 1983; 98:593–597prevent lung injury, as measured by better post-CPB 2 Messent M, Sullivan K, Keogh BF, et al. Adult respiratorypulmonary histology and lung function, as well as distress syndrome following cardiopulmonary bypass: inci-lower plasma malondialdehyde levels. In infants dence and prediction. Anaesthesia 1992; 47:267–268 3 Asimakopoulos G, Smith PL, Ratnatunga CP, et al. Lungundergoing CPB, better-preserved lung function (ie, injury and acute respiratory distress syndrome after cardio-an increased Pao2/fraction of inspired oxygen ratio pulmonary bypass. Ann Thorac Surg 1999; 68:1107–1115and shorter intubation time) was observed in a PA 4 Macnaughton PD, Evans TW. The effect of exogenousperfusion group compared with control subjects.96 surfactant therapy on lung function following cardiopulmo- Richter and colleagues97 have reported an attenu- nary bypass. Chest 1994; 105:421– 425 5 Taggart DP, El-Fiky M, Carter R, et al. Respiratory dysfunc-ated cytokine response (ie, IL-6 and IL-8) and tion after uncomplicated cardiopulmonary bypass. Ann Tho-better-preserved lung function (ie, less pulmonary rac Surg 1993; 56:1123–1128shunting, improved P[A-a]O2 levels and respiratory 6 Kochamba GS, Yun KL, Pfeffer TA, et al. Pulmonary abnor-indexes, and earlier extubation) in patients undergo- malities after coronary arterial bypass grafting operation:ing bilateral extracorporeal circulation (ie, the Drew- cardiopulmonary bypass versus mechanical stabilization. Ann Thorac Surg 2000; 69:1466 –1470Anderson technique). Whether the observed bene- 7 Chaney MA, Nikolov MP, Blakeman B, et al. Pulmonaryfits resulted from maintaining lung ventilation and effects of methylprednisolone in patients undergoing coro-PA perfusion or from the avoidance of an extracor- nary artery bypass grafting and early tracheal extubation.poreal oxygenator needs further clarification. An- Anesth Analg 1998; 87:27–33other recent study99 in a canine model demonstrated 8 McGowan FX Jr, Ikegami M, del Nido PJ, et al. Cardiopul- monary bypass significantly reduces surfactant activity inthat the use of biventricular CPB helped in preserv- children. Thorac Cardiovasc Surg 1993; 106:968 –977ing lung function (ie, reduced pulmonary vascular 9 Royston D, Minty BD, Higenbottam TW, et al. The effect ofresistance and extravascular lung water, with im- surgery with cardiopulmonary bypass on alveolar-capillary1274 Reviews Downloaded from at New York University Medical Center on September 1, 2006
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  10. 10. Pulmonary Dysfunction After Cardiac Surgery* Calvin S.H. Ng, Song Wan, Anthony P.C. Yim and Ahmed A. Arifi Chest 2002;121;1269-1277 DOI: 10.1378/chest.121.4.1269 This information is current as of September 1, 2006Updated Information Updated information and services, including high-resolution& Services figures, can be found at: This article cites 98 articles, 49 of which you can access for free at: This article has been cited by 21 HighWire-hosted articles: lesPermissions & Licensing Information about reproducing this article in parts (figures, tables) or in its entirety can be found online at: Information about ordering reprints can be found online: alerting service Receive free email alerts when new articles cite this article sign up in the box at the top right corner of the online article.Images in PowerPoint format Figures that appear in CHEST articles can be downloaded for teaching purposes in PowerPoint slide format. See any online article figure for directions. Downloaded from at New York University Medical Center on September 1, 2006