20051129 atelectasis

REVIEW ARTICLE

David C. Warltier, M.D., Ph.D., Editor

Anesthesiology 2005; 102:83854 2005 American Society of Anesthesiologists, Inc. Lippincott Williams & Wilkins, Inc.

Pulmonary Atelectasis

A Pathogenic Perioperative EntityMichelle Duggan, M.B.,* Brian P. Kavanagh, M.B.

This article has been selected for the AnesthesiologyCME Program. After reading the article, go to http://www.asahq.org/journal-cme to take the test and apply forCategory 1 credit. Complete instructions may be found inthe CME section at the back of this issue.

Atelectasis occurs in the dependent parts of the lungs of mostpatients who are anesthetized. Development of atelectasis isassociated with decreased lung compliance, impairment of ox-ygenation, increased pulmonary vascular resistance, and devel-opment of lung injury. The adverse effects of atelectasis persistinto the postoperative period and can impact patient recovery.This review article focuses on the causes, nature, and diagnosisof atelectasis. The authors discuss the effects and implicationsof atelectasis in the perioperative period and illustrate howpreventive measures may impact outcome. In addition, theyexamine the impact of atelectasis and its prevention in acutelung injury.

IT has been known for decades that in patients withpreviously normal lungs, general anesthesia is associatedwith impaired oxygenation.1 Pulmonary atelectasis wassuspected as the major cause, based on the observationof a successive decrease in lung compliance and thepartial pressure of arterial oxygen (PaO2), both of whichreturned toward normal after deep inflations of thelung.2 Bendixen et al.2 thus demonstrated their conceptof a progressive alveolar collapse during general anes-thesia with mechanical ventilation. It is now known thatatelectasis occurs in the most dependent parts of thelung of 90% of patients who are anesthetized and playsan important role in gas exchange abnormalities andreduced static compliance associated with acute lung

injury (ALI).3 This article reviews the causes, nature, andconsequences of atelectasis, focusing on the role ofatelectasis in development of perioperative morbidity,and illustrates how preventive measures could impactperioperative health. In addition, we discuss the impactof atelectasis and of its prevention in ALI.

Etiology and Pathogenesis of Atelectasis

Three sets of mechanisms have been proposed thatmay cause or contribute to the development of atelecta-sis,4 including compression of lung tissue, absorption ofalveolar air, and impairment of surfactant function. Thissection describes these three underlying physiologiccauses of atelectasis; clinical factors that can modulatethe development of atelectasis are described in a subse-quent section.

Compression AtelectasisCompression atelectasis occurs when the transmural

pressure distending the alveolus is reduced to a level thatallows the alveolus to collapse. The diaphragm normallyseparates the intrathoracic and abdominal cavities and,when stimulated, permits differential pressures in theabdomen and chest. After induction of anesthesia, thediaphragm is relaxed and displaced cephalad and istherefore less effective in maintaining distinct pressuresin the two cavities. Specifically, the pleural pressureincreases to the greatest extent in the dependent lungregions (fig. 1) and can compress the adjacent lungtissue. This is termed compression atelectasis.5

Several lines of evidence support a role of the dia-phragm in this setting. Froese and Bryan6 used cinera-diography to demonstrate a cephalad shift of the dia-phragm during anesthesia and spontaneous breathing,which did not progress after muscle relaxation. How-ever, a difference in the pattern of diaphragmatic move-ment was noted. In supine patients, during spontaneousbreathing, the lower, dependent portion of the dia-phragm moved the most, whereas with muscle paralysis,the upper, nondependent part showed the largest dis-placement. Two distinctly different patterns of diaphrag-matic displacement were seen from the same new func-

* Clinical Research Fellow, Associate Professor, Departments of Anesthesiaand Critical Care Medicine and the Lung Biology Program, Hospital for SickChildren. Department of Anesthesia and the Interdepartmental Division of Crit-ical Care Medicine, University of Toronto.

Received from the Departments of Anesthesia and Critical Care Medicine andthe Lung Biology Program, Hospital for Sick Children, Toronto, Ontario, Canada,and the Department of Anesthesia and the Interdepartmental Division of CriticalCare Medicine, University of Toronto, Toronto, Ontario, Canada. Submitted forpublication December 30, 2003. Accepted for publication August 20, 2004.Supported by the Canadian Institutes of Health Research, Ottawa, Ontario,Canada, and a Premiers Research Excellence Award from the Ontario Ministry ofScience and Technology, Toronto, Ontario, Canada.

Address reprint requests to Dr. Kavanagh: Department of Critical Care Medi-cine, Hospital for Sick Children, 555 University Avenue, Toronto, Ontario, Can-ada M5G 1X8. Address electronic mail to: [email protected].

Anesthesiology, V 102, No 4, Apr 2005 838

tional residual capacity (FRC) position. In ananesthetized patient breathing spontaneously, the activetension in the diaphragm is capable of overcoming theweight of the abdominal contents, and the diaphragmmoves the most in the lower, dependent portion (be-cause the lower or posterior diaphragm is stretchedhigher into the chest, it has the smallest radius of curva-ture and therefore contracts most effectively). In addi-tion, the diaphragm is thicker posteriorly than anteriorly,and this may account for the disproportionate move-ment.7 During paralysis and positive-pressure ventila-tion, the passive diaphragm is displaced by the positivepressure preferentially in the upper, nondependent por-tion (where there is least impedance to diaphragmaticmovement). Subsequent studies confirmed these find-

ings and, in addition, documented a reduction in thetransverse area of the chest.8 Using an advanced com-puted tomography (CT) scanner, Krayer et al.9 demon-strated a reduced thoracic cross-sectional area in anes-thetized subjects but had more variable results regardingshape and position of the diaphragm; some subjectsshowed a cranial shift of the diaphragm, but in othersubjects, part of the diaphragm was unaffected or evenmoved caudally. Other investigators have also shownresults inconsistent with the classic model of regionalventilation10; nevertheless, it can be concluded that FRCis reduced in the anesthetized subject, whether causedby loss of traction of the chest wall or compression ofthe lung. Loss of intercostal muscle function may alsocontribute to reduced FRC during anesthesia. Inhalation

Fig. 1. (A and B) In normal lungs (A), thealveolar inflation and vascular perfusionare associated with low stress and are notinjurious. Two separate barriers form thealveolarcapillary barrier, the microvas-cular endothelium, and the alveolar epi-thelium. In contrast, with atelectasis (B),alveolar inflation and deflation may beheterogeneous, and the resulting airwaystress causes epithelial injury. Becausethe blood vessels are compressed, perfu-sion may be traumatic because of flow-induced disruption of the microvascularendothelium. Both epithelial and endo-thelial injury may initiate or propagatelung injury. This figure depicts the ad-vanced stage of lung injury caused by at-electasis. The initial injury is simple col-lapse of alveoli. However, with time, thisleads to an inflammatory reaction. As thederecruited lungs cause epithelial injuryand loss of epithelial integrity, both typeI and type II alveolar cells are damaged.Injury to type II cells disrupts normalepithelial fluid transport, impairing theremoval of edema fluid from the alveolarspace. In addition to collapse, dere-cruited lungs also become fluid filled.Neutrophils adhere to the injured capil-lary endothelium and migrate throughthe interstitium into the alveolar air-space. In the airspace, alveolar macro-phages secrete cytokines, interleukin(IL)-1, -6, -8, and -10, and tumor necrosisfactor (TNF)-, which act locally to stim-ulate chemotaxis and activate neutro-phils. IL-1 can also stimulate the produc-tion of extracellular matrix byfibroblasts. Neutrophils can release oxi-dants, proteases, leukotrienes, and otherproinflammatory molecules, such asplatelet-activating factor (PAF). MIF macrophage inhibitory factor.

839ATELECTASIS AND LUNG INJURY

Anesthesiology, V 102, No 4, Apr 2005

agents decrease intercostal muscle activity, particularlyin children.11

Hedenstierna et al.8 also noted an additional source oflung compression in that there was a net shift of centralblood volume from the thorax, which seemed to pool inthe abdomen, resulting in additional dependent pressurearising from the abdomen and acting on the diaphragm.Finally, the displacement of the diaphragm has beenstudied under dynamic conditions, whereby increases indiaphragm tension through phrenic nerve stimulationhave been shown to reduce the amount of atelectasis atisovolumic conditions in anesthetized patients.12

Therefore, compression atelectasis occurs during gen-eral anesthesia and is caused by chest geometry, overallcephalad diaphragm displacement, differential regionaldiaphragmatic changes, shift of thoracic central vascularblood into the abdomen, and altered diaphragmaticdynamics.

Gas ResorptionResorption atelectasissometimes called gas atelecta-

sis4can occur by two mechanisms. After completeairway occlusion, a pocket of trapped gas is created inthe lung unit distal to the obstruction. Because gas up-take by the blood continues and gas inflow is preventedby blocked airways, the gas pocket collapses.13 Underthese conditions, the rate of absorption of gas from anunventilated lung area increases with elevation of thefraction of inspired oxygen (FIO2).

14

A somewhat different mechanism explains absorptionatelectasis in the absence of airway occlusion. In thiscontext, lung zones that have low ventilation relative toperfusion (low ventilation/perfusion [VA/Q] ratio) have alow partial pressure of alveolar oxygen (PAO2) when airis breathed. When the FIO2 is increased, PAO2 increases,causing the rate at which oxygen moves from the alve-olar gas to the capillary blood to increase greatly. Theoxygen flux may increase so much that the net flow ofgas into the blood exceeds the inspired flow of gas, andthe lung unit becomes progressively smaller. Collapse ismost likely to occur when the FIO2 (and duration ofexposure) is high or where the VA/Q ratio (and mixedvenous oxygen content) is low.15,16

Surfactant ImpairmentPulmonary surfactant that covers the large alveolar

surface is composed of phospholipids (mostly phos-phatidylcholine), neutral lipids, and surfactant-specificapoproteins (termed surfactant proteins A, B, C, and D).By reducing alveolar surface tension, pulmonary surfac-tant stabilizes the alveoli and prevents alveolar collapse.This stabilizing function of surfactant may be depressedby anesthesia, and such an effect has been confirmed invitro by Woo et al.17 The authors evaluated the effect ofanesthetic agents on surfactant function using deflationpressurevolume curves in excised dog lungs. They

found that the reduction in percent maximum lungvolume was proportional to the concentration of bothchloroform and halothane.17 Wollmer et al.18 also usedpulmonary clearance of technetium-labeled diethylene-triamine pentaacetic acid to demonstrate that halothaneanesthesia, in combination with high oxygen concentra-tion, caused increased permeability of the alveolarcap-illary barrier in rabbit lungs. The authors postulated thatthe increased rate of pulmonary clearance of techne-tium-labeled diethylenetriamine pentaacetic acid duringanesthesia with halothane was likely to be caused bycombined effects on the pulmonary surfactant or thealveolar epithelium or both.18 In addition, it is knownthat the content of alveolar surfactant in isolated lungs ismodified by mechanical factors. Hyperventilation by in-creased tidal volume,19 sequential air inflations to totallung capacity,20 or even a single cycle of increased tidalvolume19 all cause release of surfactant in isolated animallungs. In rabbits, maintained increases in tidal volumeincreased the amount of total phospholipids recoveredfrom bronchoalveolar lavages.21,22 Supporting this is thereport that the spontaneous occurrence of large gaspingrespirations increases the proportion of active forms ofalveolar surfactant (phospholipids). Oyarzun et al.23 ex-amined the ventilatory variables of cats breathing spon-taneously during anesthesia for 4 h. They found that thefrequency of large gasps is directly correlated with theconcentration of phospholipids in bronchoalveolar la-vage fluid.23

All three mechanismscompression, gas resorption,and surfactant impairmentmay contribute to atelecta-sis formation during general anesthesia (fig. 2). How-ever, given the surfactant reserve and the 14-h surfactantturnover time, it may be that primary changes in surfaceforces are less important; it is not known whether acollapsed alveolus can denature surfactant, and so the14-h turnover time may not be relevant. Nonetheless,absorption and compression are considered to be thetwo mechanisms most implicated in perioperative atel-ectasis formation.24

Fig. 2. This schematic outlines the probable pathogenic mech-anisms underlying the development of atelectasis. FIO2 frac-tion of inspired oxygen; IV intravenous; VA/Q ventilation/perfusion ratio.

840 M. DUGGAN AND B. P. KAVANAGH


Nature of AtelectasisThe following section reviews the characteristics of

atelectasis in several clinical contexts and then reviewscontemporary concepts regarding the nature ofatelectasis.Atelectasis due to Anesthesia. Anesthesia-induced

atelectasis is traditionally thought of as collapse of alve-oli. Brismar et al.5 showed that within 5 min after induc-tion of anesthesia, areas of increased density appeared inthe dependent regions of both lungs on CT. The denseareas had an attenuation factor that corresponds toblood and connective tissue and indicates the absence ofair. Injection of radiocontrast in the pleural spaceshowed that the densities were located above the pleura,i.e., within the lung.25 Hedenstierna et al.26 also foundthese densities in anesthetized sheep and confirmed his-tologically that the densities were collapsed lung regionsand not fluid accumulation.

Methods to restore normal FRC and various reexpan-sion maneuvers have been suggested. The application ofpositive end-expiratory pressure (PEEP) has been testedin several studies. Arterial oxygenation does not usuallyimprove markedly, and atelectasis may persist.27,28 Re-opened units recollapse rapidly after discontinuation ofPEEP. However, Rothen et al.29,30 demonstrated in vol-unteers that peak inspiratory pressures of at least 40 cmH2O were needed to fully reverse anesthesia-induced col-lapse of healthy lungs, and most of the reexpanded atelec-tatic lung tissue remains inflated for at least 40 min.Direct Visualization of Atelectasis. Using a unique

in vivo microscopic technique, Halter et al.31 viewedalveoli in the living animal in real time during mechanicalventilation. In a surfactant deactivation model of acuterespiratory distress syndrome (ARDS), they measuredalveolar number and stability before, during, and after arecruitment maneuver with ventilation with either de-creased or increased PEEP. They demonstrated that arecruitment maneuver opens atelectatic alveoli and thatwithout adequate PEEP, alveoli are unstable and suscep-tible to derecruitment. Although associated with sam-pling limitations,32 this elegant study was the first todirectly demonstrate visual evidence of collapse of indi-vidual alveoli reflecting atelectasis and stabilization re-flecting recruitment.32

Cyclic Lung Recruitment. Mechanical ventilation ofareas of lung that are atelectatic is associated with repet-itive collapse and reexpansion with each breath, oftencalled cyclic recruitment. A conventional view of theeffects of atelectasis on gas exchange conveys an imageof mixed venous blood perfusing nonventilated or col-lapsed alveoli, resulting in a consistent and stable pro-portion of the pulmonary venous return that derivesfrom deoxygenated blood.33 This notional contribution(i.e., deoxygenated blood added to oxygenated blood) isseen as the sum of two constant flow rates, resulting in

a shunt fraction (Qs/Qt %)7 that can be mathematically

calculated.However, we now know that the oxygen content of

pulmonary venous blood varies significantly throughoutthe respiratory cycle as the shunt fraction changes withevery breath. Baumgardner et al.34 tested the hypothesisthat cyclic collapse of alveoli in dependent lung regionswith every breath should lead to large oscillations inPaO2 as shunt varies with the respiratory cycle. Theyplaced a partial pressure of oxygen (PO2) probe in thebrachiocephalic artery of rabbits after saline lavage. Theyfound a significant effect of respiratory rate on the mag-nitude of oscillations; as the respiratory rate increased,the amplitude of oscillations became progressively small-er.32 The higher respiratory rate avoided cyclic recruit-ment; i.e., the shorter expiratory time allowed expirationwithout collapse. In practice, the beneficial effect ofhigher respiratory rates leading to improved oxygen-ation can be seen when ventilating pediatric patients andin particular neonates. This suggests that the dynamics ofmechanical events leading to recruitment and derecruit-ment are important determinants of the amount of lungthat is cyclically recruited.34 A previous study by Wil-liams et al.35 also showed within-breath arterial PO2 os-cillations in an animal model of ARDS and confirmed thatPaO2 oscillations occur in the atelectatic lung. The au-thors investigated the effect of PEEP on PaO2 oscillations.They found that as PEEP was increased, the amplitude ofthe PaO2 oscillation decreased and the mean PaO2 in-creased.35 Several studies have evaluated the effects ofvarious inspiratory-to-expiratory ratios on gas exchange,lung mechanics, and FRC; the inspiratory-to-expiratoryratio per se was not found to be a significant factor.3638

Atelectasis: Volume Loss versus Fluid Filling.More recently, it has been argued that the dependentinjured lung is derecruited, not because it is collapsedbut because it is filled with fluid.39 Work by Gattinoni etal.4042 had concluded that dependent portions of theinjured lung are exposed to a compressive pressure fromthe increased weight of edematous lung and are col-lapsed. Such a weight-of-the-lung hypothesis has beenstudied, and it seems that the weight of the lung ac-counts for only approximately 20% of the vertical gradi-ent in pleural pressure and alveolar volume in normallungs.4345 Hubmayr39 suggests an alternative view ofthe mechanics of injured lungs based on lung weight,shape matching, interpretation of CT images of the lung,and pressurevolume curves. For example, whereedema fluid and foam fill dependent regions, high infla-tion pressures are required to inflate with air, as opposedto low pressures required for inflation with fluid. Thepressurevolume characteristics of the former moreclosely display the classic findings associated with atel-ectasis, including the prominent lower inflection pointreflecting opening pressure.39 Evidence in support ofedema as the source of regional impedance in ARDS



include parenchymal marker studies in oleic acidin-jured lungs.46 The parenchymal marker technique de-scribes the topographic distribution of regional volumeand ventilation in laboratory animals. The authors foundthat oleic acid injury did not produce collapse of depen-dent lung units in this model of ARDS.46 They proposedan alternative mechanism for the topographic variabilityin regional impedances and lung expansion after injury,which was liquid or foam in alveoli and conductingairways.46

Factors Modulating the Formation of AtelectasisIt is important for clinicians to understand how atel-

ectasis develops or worsens in the clinical context. Sev-eral important clinical events act as modifiers that influ-ence the formation of atelectasis (fig. 2).Type of Anesthesia. Atelectasis develops with both

intravenous and inhalational anesthesia, regardless ofwhether the patient is breathing spontaneously or isparalyzed and mechanically ventilated.4749 Ketamine isthe only anesthetic that does not produce atelectasiswhen used alone, although in conjunction with neuro-muscular blockade, it does result in atelectasis.50

Ventilatory effects of regional anesthesia depend onthe type and extension of motor blockade.4 Neuroaxialblockade that has significant cephalad extension reducesinspiratory capacity by up to 20%, and expiratory reservevolume approaches zero51; less extensive blockade af-fects pulmonary gas exchange only minimally, and arte-rial oxygenation and carbon dioxide elimination are wellmaintained during most spinal and epidural anesthe-sia.52,53 Closing capacity and FRC remain unchanged.54

Impact of Time. The maximum decrease in FRCseems to occur within the first few minutes of generalanesthesia.5,55 During anesthesia for surgical operationson the limb, FRC is not influenced further by depth orduration of anesthesia.55,56 Don et al.55 studied patientsundergoing peripheral limb surgery who were free ofcardiac and respiratory disease. Patients were dividedinto two groups, those breathing halothane in 100%oxygen and those breathing halothane in 30% oxygen innitrogen. The FRC decreased comparably in both groupsafter induction of anesthesia, but this did not progresswith time. However, other studies have found that dur-ing abdominal or thoracic surgery, pulmonary gas ex-change deteriorates progressively during the course ofthe operation57,58; these studies were unable to deter-mine the independent impact of time on atelectasis asopposed to surgical manipulation (e.g., surgical packing,tissue retraction).Effects of Position. In adults, changing from the

upright to the supine position results in a decrease of0.5 l in FRC to 1.0 l, even in the awake state.7 Afteranesthesia, FRC is reduced by a further 0.5 l to 0.7 l.49

The Trendelenburg position allows the abdominal con-tents to push the diaphragm further cephalad, resulting

in a further decrease in FRC.59 In the lateral decubitusposition, the dependent lung is predisposed to atelecta-sis, whereas the nondependent lung may have an in-creased FRC. The overall result is usually a slight increasein total lung FRC, which, despite the differences in lungsize, is independent of whether the right or the left lungis in the dependent position.60 The prone position mayincrease FRC slightly,61 although this may not decreaseatelectasis. In fact, distribution of ventilation is moreuniform in anesthetized patients in the prone position,in particular where the abdomen is not supported.62

Prone positioning improves oxygenation in patientswith ARDS.63 Animal models have also demonstrated thebenefit of prone positioning after oleic acidinducedlung injury as well as a model of lung injury inducedsolely by mechanical forces.64,65 Prone positioningcauses less extensive histologic injury and alters itsdistribution.64,65

Atelectasis is more prominent after cardiac surgerywith cardiopulmonary bypass (CPB) than after otherforms of surgery. Using a porcine model, Magnusson etal.66 found that atelectasis is produced to a much largerextent after CPB than after anesthesia alone or withsternotomy. Furthermore, the CPB-associated atelectasisaccounted for most of the marked post-CPB increase inshunt and hypoxemia.66 Clinical experience is consis-tent with laboratory reports, and prominent atelectasishas been noted in the dorsal lung regions on the firstpostoperative day in cardiac surgery patients.67 Othercauses of gas exchange impairment after sternotomy andCPB have been investigated, including pulmonary endo-thelial permeability.68 Macnaughton et al.68 did not findany increase in pulmonary endothelial permeability, andthey hypothesized that the major component of thedeterioration in lung function was probably atelectasisoccurring during bypass. Numerous studies have shownthat a lung recruitment strategy and PEEP improves ox-ygenation in patients after CPB.69,70 In addition, theapplication of PEEP of 10 cm H2O during CPB to main-tain lung inflation has been shown to be beneficial.71

Many anesthetists intentionally inflate the patients lungsbefore coming off CPB and directly visualize equal ex-pansion of the lungs. This simple maneuver may detectsignificant obstruction from secretions or blood in theendotracheal tube.Inspired Oxygen. High oxygen concentration has

been associated with atelectasis formation, and this isimportant because use of high FIO2 (i.e., approaching1.0) represents standard practice among many anesthe-siologists.72 Previous studies suggested that inspired ox-ygen concentration may not be an important indepen-dent predictor of anesthesia-associated atelectasis.5,55

However, one of these studies used the helium-dilutiontechnique to measure FRC, which may not be as sensi-tive as the CT that was used in later studies.55,73 In theabsence of preoxygenation, atelectasis is not seen di-



rectly after induction of anesthesia; however, when FIO2is increased to 1.0 before intubation, development ofatelectasis is a consistent finding.74,75 Concerns aboutoxygen-induced atelectasis are not restricted to induc-tion of anesthesia; increasing FIO2 at the end of surgery to1.0 before extubation also causes additional atelectasis,which persists into the postoperative period.76 How-ever, the use of lower FIO2 may increase the risk ofhypoxemia, should airway management subsequentlyprove difficult and ventilation be threatened.77 Onestudy investigated how different oxygen concentrationsmay affect the formation of atelectasis and the decreasein arterial oxygen saturation during apnea.78 The authorsfound that during routine induction of general anesthe-sia, 80% oxygen caused minimal atelectasis, but the timemargin before desaturation occurred was significantlyshortened compared with that of 100% oxygen.78 Inaddition, evidence suggests that administration of sup-plemental oxygen reduces the incidence of wound in-fection and could be beneficial during anesthesia andrecovery.79,80 Another possible benefit of supplementaloxygen during anesthesia includes a reduced incidenceof postoperative nausea and vomiting after colorectalsurgery,81 although this was not found in patients under-going gynecologic laparoscopy.82

The effects of nitrous oxide on lung volumes duringanesthesia have also been studied.8385 There was nodifference in the incidence of postoperative atelectasis ifnitrous oxide in oxygen was used or if air in oxygen wasused as the inspired gas.

In treating patients for induction of general anesthesia,anesthesiologists must trade off the very rare possibilityof acute hypoxemia in the event of difficulty with airwaymanagement versus the common and predictablebutgenerally mildimpact of hyperoxia-induced atelectasison later intraoperative gas exchange. Therefore, the useof a lower FIO2 to replace preoxygenation has not beenrecommended as a new standard in clinical practice.78

Effects of Age. In adulthood, progressive age is notassociated with increased propensity for development ofatelectasis.86 However, in young children (aged 13 yr)atelectasis seems to develop more readily than inadults,87 possibly because of the far greater thoracic wallcompliance resulting in less outwardly directed lungdistension forces.88 In infants, contraction of the dia-phragm may cause paradoxical inward movement of thehighly deformable chest wall, resulting in loss of lungtraction. The resultant atelectasis could reduce ventila-tory efficiency, increase diaphragmatic fatigue, andthereby further increase the tendency for atelectasis de-velopment. In addition, type I and II muscle fibers arenot fully developed in children who are younger than 2yr. This makes them prone to respiratory failure andfatigue when there is extra stress put on their respiratorysystem, not only during general anesthesia89 but also in

the presence of a respiratory tract infection, epiglottitis,or airway obstruction.

Closing volume is also greater in young children inwhom the elastic supporting structure of the lung isincompletely developed. This puts the infant at greaterrisk for atelectasis because airway closure can occureven during tidal breathing.24 The closing volume plusthe residual volume constitutes the closing capacity. IfFRC is decreased relative to closing capacity, this con-verts normal areas of lung to low VA/Q areas and com-pounds the propensity for development of atelectasis.90

Body Habitus. Obesity worsens arterial oxygenationthrough multiple mechanisms,91 of which developmentof atelectasis is an important contributor. This is becauseof a markedly reduced FRC promoting airway closure toa greater extent than in healthy-weight subjects.92 As theweight of the torso and abdomen make diaphragmaticexcursions more difficultespecially when recumbentor supinethe FRC decreases, and this is intensified inthe setting of diaphragmatic paralysis associated withneuromuscular blockade. Don et al.55 further clarifiedthe effect of body size on gas exchange and showed thatan individual with an increased weight/height ratio (i.e.,obese) would be at a particular disadvantage in thesupine position because closing volume is increased inrelation to FRC. Pelosi et al.93 also investigated the ef-fects of body mass index on FRC, respiratory mechanics,and gas exchange during general anesthesia. They foundthat with increasing body mass index (i.e., ratio of bodyweight/surface area), FRC and lung compliance de-creased, and the oxygenation index (PaO2/PAO2) de-creased exponentially.93 Prone positioning, although diffi-cult in obese patients, may improve oxygenation.63

Consistent with the effects of obesity, the reduced FRC thatoccurs during pregnancy also potentiates atelectasis.94

Tidal Volume. The ARDSnet study recommends theuse of low tidal volume in patients with ARDS.95 Lowertidal volume reduces stretch-induced lung injury in pa-tients with ARDS,96 and this approach is translated intoimproved patient survival.95,97 However, extrapolationof the low-tidal-volume approach to patients withoutlung injury (or ARDS) requires caution for two principalreasons. First, it has been long recognized that low tidalvolume increases the development of atelectasis in theabsence of lung injury.2,98100 Therefore, generalizedadoption of low tidal volume in patients without preex-isting lung injury (e.g., during general anesthesia) couldpromote development of atelectasis. Second, in the pres-ence of ARDS, the ARDSnet protocol is specific: The datastipulate 6 ml/kg (vs. 12 ml/kg) in the context of aprecise ventilatory management protocol that stipulatesmany ventilatory parameters, in addition to tidal vol-ume.95 A recent study has suggested that the specificlow-tidal-volume approach used in the ARDSnetstudy95 was actually associated with the development ofintrinsic PEEP,97 raising the possibility that recruit-



mentnot simply low tidal stretchplayed a protectiverole in these patients. Therefore, if a low tidal volumestrategy is used that does not result in the developmentof intrinsic PEEP, the propensity for development ofatelectasis might be significant. The use of low tidalvolume in the absence of recruitment or PEEP in anes-thetized patients without lung injury may lead to atelec-tasis and is not recommended.

Two practical points are important regarding mode ofventilation during general anesthesia. In contrast to vol-ume-controlled ventilation, pressure-controlled ventila-tion results in smaller delivered tidal volumes whenrespiratory system compliance is decreased (e.g., duringsurgical retraction or in the presence of abdominalpacks). Smaller tidal volumes may lead to atelectasis andmay go undiagnosed because there is no change in thepeak airway pressure as pressure-controlled ventilationis being used. In addition, fresh gas flow may have animpact because with older volume-controlled ventila-tors, increased fresh gas flow results in increased deliv-ered tidal volume.101

Preexisting Lung Disease. Smokers and patientswith lung disease show more pronounced gas exchangeimpairment in the awake state than healthy subjects do,and this difference also persists during anesthesia.102

However, only a small shunt and almost no atelectasisdevelops in these patients, but they may have severeVA/Q mismatch. Hyperinflation of the lungs may makethem resist collapse.103 The chronic hyperinflated stateof the lungs in chronic bronchitis changes the mechan-ical behavior of the lungs and the interaction with thechest wall so that the tendency to collapse is reduced.However, patients with chronic obstructive lung diseasemay have large regions with low VA/Q ratios that canresult, over time, in resorption atelectasis.4

Effects of AtelectasisDevelopment of atelectasis is associated with the de-

velopment of several pathophysiologic effects, includingdecreased compliance, impairment of oxygenation, in-creased pulmonary vascular resistance, and develop-ment of lung injury.Decreased Compliance. One of the first articles ex-

amining the effects of atelectasis was by Mead and Col-lier99 in 1959. They noted that when anesthetized dogswere allowed to breathe spontaneously or were para-lyzed and ventilated at tidal volumes of approximately12.5 ml/kg, pulmonary compliance decreased progres-sively. They found that these changes were immediatelyreversed after forced inflations of the lungs, whereasforced deflations caused further compliance reductions.The appearance of the lungs as well as measurement oftotal and ventilatory lung volumes indicated that thelungs were atelectatic.99

These laboratory findings were translated into the peri-operative context with the article by Bendixen et al.,2

which reported that atelectasis caused a decrease inpulmonary compliance in surgical patients and was as-sociated with a worsening in systemic oxygenation. Thedecreased compliance is conventionally considered tobe due to a reduction in lung volume, such that inspira-tionexpiration cycles commencing from a lower FRCare completed on a less efficient section of the notionalpressurevolume curve.104 Therefore, greater energy isconsumed because a given change in transpulmonarypressure results in a lesser tidal volume because of thesigmoid shape of the pressurevolume curve. An ana-tomical basis has been suggested for such atelectasis-associated decreased FRC in the context of general an-esthesia (see Compression Atelectasis).6

The pressurevolume characteristics of the lung deter-mine the work of breathing, and ventilatory work maybe analyzed by plotting pressure against volume.105 Inthe presence of increased airway resistance or decreasedlung compliance, increased transpulmonary pressure isrequired to achieve a given tidal volume with conse-quent increase in the work of breathing.

Although the concept of altered compliance has beenwell established in the setting of macroatelectasis (e.g.,lobar or dependent atelectasis sufficiently large to beradiologically apparent), there are no data regardingwhether microatelectasis (e.g., after brief exposure toincreased FIO2 during preoxygenation

75) has comparableeffects on lung mechanics.Impaired Oxygenation. In many situations, the most

striking effect of atelectasis is impairment of systemicoxygenation. This was first identified in the context ofgeneral anesthesia2 where the use of passive hyperinfla-tions reversed the hypoxemia.2 Others reported impair-ment of oxygenation during prolonged constant-volumeventilation using small tidal volumes in the absence ofintermittent hyperinflations.106108

Atelectasis can occur as a result of hyperoxia.75,109 Ifhigh FIO2 is continued, the effects may not be noted byobserving pulse oximetry, but only if PaO2 is measured.In this situation, the impaired oxygenation can be ex-pressed in terms of PaO2. The cause of the impairedoxygenation has been shown, using the multiple inertgas technique, to result from increased mismatch ofventilation with perfusion.75

Two approaches have been shown to mitigate againstthe development of hypoxia. First, as demonstrated orig-inally, intermittent hyperinflation maneuvers reverse theeffect on gas exchange.2 Maintenance of lung volumefrom the outset can prevent, as opposed to reverse,development of intraoperative atelectasis.28 Second, al-though recognized as an issue for decades, the compo-sition of the inspired gases used during induction ofgeneral anesthesia has been shown to directly impactthe development of microatelectasis in healthy patientsundergoing general anesthesia,75 as well as in patientswith lung injury.110 Rothen et al.75 found that very little



atelectasis occurred after the induction of general anes-thesia in subjects whose lungs were ventilated with 30%oxygen in nitrogen. Furthermore, the increase in theamount of atelectasis was less rapid in the setting of 30%oxygen (in nitrogen) compared with 100% oxygen. Thisis consistent with the notion that a poorly absorbed gassuch as nitrogen might prevent the early formation ofatelectasis and, conversely, that use of a highly absorbedgas (e.g., oxygen) would enhance the development ofatelectasis.Pulmonary Vascular Resistance. Early studies sug-

gested that the pulmonary vascular resistance was min-imal at FRC. Lung volume much above this notionalvalue resulted in alveolar compression due to lungstretch, whereas lung volume falling below the FRC wasthought to result in compression of extraalveolar vessels.Therefore, this notion explained the changes in pulmo-nary vascular resistance on the basis of physical alter-ation of the pulmonary blood vessels, either stretchingor narrowing caused by increased lung volume or com-pression caused by decreased lung volume.111113 How-ever, regional hypoxia develops in atelectatic lungs, andit has been shown that the mechanism of increased largevessel pulmonary vascular resistance in the lungs is dueto hypoxic pulmonary vasoconstriction, due in turn todecreased alveolar and mixed venous oxygen ten-sion.114116 Recent work by our group has demonstratedthat this significant increase in vascular resistance canoccur in previously normal lungs in an experimentalsetting, resulting in right ventricular dysfunction andincreased microvascular leakage.117

Lung Injury. Extensive evidence has established theimportance of maintenance of lung volume in the pre-vention of lung injury. The pivotal publication by Webband Tierney118 demonstrated that application of PEEPprevented the development of lung injury induced byextremely high tidal volume. The specific degree ofatelectasis responsible for attenuation or prevention ofhigh tidal volumeinduced lung injury was explored bySandhar et al.119 and Muscedere et al.120 using differentexperimental models over 5- and 2-h time periods, re-spectively. In isolated, nonperfused lungs that are venti-lated with no or low PEEP, reductions in compliance andevidence of morphologically apparent lung injury occur.Permitting such atelectasis in the presence of high tidalvolumes is associated with hyaline membrane formation,along with regional inhomogeneity of atelectasis andoverdistension. Other articles have also demonstratedthat repetitive lung collapse or atelectasis leads to in-creased neutrophil activation in previously injuredlungs.121,122 In addition to lung injury induced by ex-tremely high tidal volumes, ventilation at low lung vol-umes worsens lung injury by repeated small airway clo-sure.123,124 The concept of permissive hypercapniadeveloped to avoid lung injury caused by high tidalvolumes or high inflation pressures. Higher end-tidal

carbon dioxide levels may be accepted to reduce vo-lutrauma or barotrauma, particularly in pediatricpatients.

Potentiation of lung injury by atelectasis has additionalimplications for inflammatory effects in the lung. Trem-blay et al.125 examined the effect of ventilation strategyon lung inflammatory mediators in the presence andabsence of lung injury and demonstrated that in theabsence of PEEP, an impairment in lung compliance wasaccompanied by increased cytokine concentrations (e.g.,tumor necrosis factor , interleukin 1) that were great-est in the groups pretreated with lipopolysaccharide.125

These concepts were extended to the in vivo setting,where it was reported that maximal serum cytokineconcentrations induced by high tidal volume occurred inthe context of zero PEEP. In addition, atelectasis wors-ened the impairment of compliance induced by hightidal volume.126 Perhaps of greatest concern in that pub-lication was the high mortality (in the absence of cyto-kine alterations) observed in the in vivo combination oflow-tidal-volume ventilation in the presence of atelecta-sis. These data suggest that in terms of the most mean-ingful outcome (i.e., survival), the combination of lowtidal volume and atelectasis may be the most adverseventilation strategy and that the increased cytokines ob-served in the high-tidal volume groups may be of lessimportance.126

Recent work by our group, wherein rats without lunginjury received ventilatory strategies with and withoutPEEP and recruitment maneuvers, may place these find-ings into perspective.117 We found decreased survival inthe zero-PEEP group and also demonstrated ultrastruc-tural evidence of microvascular epithelial disruption inthose animals. In addition, we demonstrated that rightventricular dysfunction, possibly secondary to increasedpulmonary vascular resistance, occurred in the presenceof reduced FRC.117

Clinical Impact of Atelectasis beyond the Operat-ing Room. Development of atelectasis intraoperativelyis associated with decreased lung compliance, impair-ment of oxygenation, increased pulmonary vascular re-sistance, and development of lung injury. The adverseeffects of atelectasis persist in the postoperative periodand can impact patient recovery. Atelectasis can persistfor 2 days after major surgery.127 Often, the lung dys-function is transient, and normal lung function resumessoon after anesthesia and surgery. For example, atelec-tasis resolves within 24 h after laparoscopy in nonobesesubjects.128 Nevertheless, patients experience perioper-ative respiratory complications that may be related toreduction in FRC.129,130

Some pulmonary complications occur during or imme-diately after anesthesiamainly hypoxemia. In a largestudy with more than 24,000 patients, 0.9% had a hy-poxemic event in the postanesthesia care unit that ne-cessitated a specific intervention other than only supple-



mental oxygen.131 There is no clear evidence thatatelectasis is the cause of all of these postoperativehypoxemic events; respiratory depression from residualanesthetic may be more likely.24 However, it seemslikely that preventing atelectasis formation during thewhole perioperative period would increase the pulmo-nary oxygen reserve, potentially reducing the likelihoodof late postoperative complications.

The characteristic postoperative mechanical respira-tory abnormality after abdominal or thoracic surgery is arestrictive pattern with severely reduced inspiratory ca-pacity, vital capacity, and FRC.132134 Patients breatherapidly with small tidal volumes and are unwillingorunableto inspire deeply. Patients in whom postopera-tive pulmonary complications develop have a relativelygreater reduction of FRC, vital capacity, and PaO2 thanthose who do not.132,134 The impact of postoperativepain control in preventing postoperative atelectasis hasbeen the focus of much research effort. Although painand muscle splinting in response to pain are traditionallyassumed to be the principal causative factors, total reliefof pain after upper abdominal surgeryusing epiduralanalgesiaresults in only partial restoration of vital ca-pacity and has minimal effect on FRC.135 However, arecent meta-analysis suggested that postoperative epi-dural opioids significantly decrease the frequency ofatelectasis but not other pulmonary complications whencompared with systemic opioids.136 Other studies havefound no difference in the incidence of pulmonary com-plications. Manikian et al.137 demonstrated that thoracicepidural analgesia in 13 patients undergoing upper ab-dominal surgery caused a significant increase in forcedvital capacity, but the FRC remained unchanged. Spenceand Logan138 reported no significant impact of postop-erative epidural analgesia on oxygenation when com-pared with patients receiving systemic morphine, andJayr et al.139 reported that although the epidural pro-vided superior postoperative analgesia, it did not affectthe frequency of postoperative pulmonary complica-tions, regardless of preoperative pulmonary status. Fi-nally, a recent multicenter randomized trial of 915 high-risk surgical patients reported a slight reduction inpostoperative pulmonary complicationsbut no impacton mortality or major morbidityattributable to epi-dural versus systemic analgesia, although this study mayhave been underpowered to examine mortality.140

Two particular aspects of pulmonary defense mecha-nisms, coughing and removal of particulate matter, areadversely affected by the changes in lung mechanics andbreathing pattern135; this may predispose to pulmonaryinfection. A number of studies examined the effects ofhalothane and thiopentone on mucociliary clearanceand found that these agents may be responsible forreduced mucous clearance in the postoperative peri-od.141143 A more recent study demonstrated that totalintravenous anesthesia with propofol, alfentanil, and ve-

curonium depressed mucociliary flow in patients withhealthy lungs.144 Cervin and Lindberg145 examined theeffects of desflurane on mucociliary activity in the rabbitmaxillary sinus in vivo. Desflurane increased mucocili-ary activity, and the authors concluded that desflurane isan airway irritating compound.145 Atelectasis and pneu-monia are often considered together because thechanges associated with atelectasis may predispose topneumonia.146 Despite a direct lack of evidence of acorrelation between atelectasis and pneumonia, reduc-ing or avoiding atelectasis may diminish postoperativepulmonary complications147 and thus improve outcome;however, this remains to be proven.

In a series of adults undergoing elective abdominalsurgery, postoperative pulmonary complications oc-curred in 9.6% of cases.148 Atelectasis and infectiouscomplications account for the majority of reported pul-monary complications,149 and the consequences includea significant burden in terms of morbidity149 and addi-tional healthcare costs.150 In some series, pulmonarycomplications account for 24% of deaths within 6 days ofsurgery,130,149 although the precise relation to atelectasisis unclear.Experimental Evidence that Atelectasis Causes

Lung Injury. The majority of studies examining theinteractions of mechanical ventilation and nonventila-tory lung injury have observed the effects of injuriousmechanical ventilation strategy on preinjured lungs.However, several experimental studies have examinedthe effect of preemptive recruitment on the effects ofsubsequent lung injury.Atelectasis Worsens Lung Injury Caused by Me-

chanical Stretch. Multiple studies have convincinglydemonstrated that recruitment provides effective protec-tion against lung injury that is either induced118,151,152 oraggravated120,125,153,154 by mechanical stretch. This mayassume increasing importance as the role of tidal volumeand plateau pressures in ARDS is debated.95,155,156

Atelectasis Worsens Lung Injury Not Caused byMechanical Stretch. Most patients with severe lunginjury require supportive mechanical ventilation. It isclear from multiple laboratory157,158 and clinical95,159

studies that stretch can cause or worsen lung injury.However, there is a vast spectrum of causes of ALI, andthere are striking similaritiesand few differencesinthe pathogenesis, pathophysiologic dysfunction, and his-tologic appearance of ALI or ARDS, whether caused bystretch158 or other etiologies.160 Therefore, because re-cruitment is effective in reducing stretch-induced injuryand because so many pathogenic and morphologic fea-tures are shared between stretch-induced versus otherforms of injury, it may be that the protective effects ofrecruitment could be applicable to lung injury that is notcaused by increased tidal stretch.

Additional specific lines of evidence exist. Inflation ofa lung graft before reimplantation, as opposed to main-



tenance of the lung in a deflated state, confers increasedviability.161163 The importance of inflation in lung pro-tection has been confirmed in in vivo162,163 and exvivo161 models and may be mediated either via reduc-tion in pulmonary vascular resistance161 (potentially de-creasing endovascular shear injury) or through preven-tion of surfactant inactivation.163 Finally, earlyapplication of mechanical ventilation may, throughmaintenance of lung volume (FRC), reduce mortality inexperimental porcine sepsis164 and in experimentalhemorrhagic shock.165

Detection of AtelectasisAtelectasis is usually suspected when alterations in

lung physiology consistent with the development ofatelectasis (e.g., decreased compliance, impaired oxy-genation) occur in a setting where atelectasis is likely.However, confirmation of atelectasis is possible througha variety of means.Conventional Chest Radiography. Lobar or seg-

mental atelectasis is classically represented as opacifica-tion of the lobe or lobar segment in question. Generalsigns of atelectasis relate to volume loss. The most directand reliable sign is the displacement of the interlobarfissure. Other signs of volume loss, such as increase ofthe hemidiaphragm and mediastinal shift, are maximalnearest the point of volume loss. Compensatory overin-flation of the remaining aerated segments in the affectedlobe is present, and the collapsed portion of the lung isof increased opacity and often triangular in at least oneprojection.166 For example, when atelectasis resultsfrom proximal bronchial occlusion, an obstruction maybe identifiable in the proximal bronchial tree, beyondwhich the tree is not aerated. If atelectasis results fromabsorption, the features are similar to consolidation,where the atelectatic lung parenchyma is opacified, andcontrasts with the patent bronchial airway.

In addition to airway characteristics, other features ofatelectasis are important. The silhouette sign allowsidentification of the lobe or segment of the lung that isaffected. It is based on the principle that apposition ofdensely atelectatic lung with an additional contiguousstructure, such as the diaphragm or the heart, results inobliteration of the boundary between the lung and theadjacent structure. For example, opacification of part ofan atelectatic lung in conjunction with obliteration ofthe ipsilateral hemidiaphragm suggests lower lobar atel-ectasis; in contrast, preservation of the hemidiaphragmindicates that the ipsilateral lower lobe is not atelectatic.

A cardinal characteristic of atelectasis is volume loss ofthe affected lobe. This is associated with secondarychanges in adjacent structures, in an attempt to fill thegap created by the loss of lung volume, and results inalterations including shift of the mediastinum or thehilum towards the affected area, elevation of the ipsilat-

eral hemidiaphragm, and secondary (or compensa-tory) emphysema in the adjacent nonatelectatic lung.

There is no doubt that conventional chest radiographscan reveal collapse in a segmental or lobar distribution.However, the ability of chest radiographs to detect atel-ectasis that occurs during general anesthesia or duringmechanical ventilation of recumbent critically ill patientsis less certain.167

Computed Tomography. Computed tomography isemerging as the preferred method for imaging the lungbecause of the widespread availability, resolution, highsignal/noise ratio for lung tissue, and speed. From con-ventional CT images, it is possible to measure whole andregional lung volumes, distribution of lung aeration, andrecruitment behavior under various clinical conditionsand interventions.168 In the 1980s, atelectasis wasshown by CT in anesthetized patients.5,169

Since then, atelectasis has been studied extensively.Atelectasis on a CT scan has been defined as pixels withattenuation values of 100 to 100 Hounsfield units.3

Hounsfield units quantify attenuation or density seen onCT. In this study, Lundquist et al.3 studied patients un-dergoing elective abdominal surgery with CT of thethorax during anesthesia. Attenuation values in histo-grams of the lung and atelectasis were studied using twomethods of calculating the atelectatic area. On the basisof the CT findings, atelectasis occurs in the most depen-dent parts of the lungs and occurs in almost 90% ofpatients who are anesthetized. The extent of the atelec-tasis in the dependent regions can be reduced by PEEP.5

The lung in ARDS is characterized by a marked in-crease in lung tissue and a massive loss of aeration.170

Gattinoni et al.40,41,171,172 have extensively investigatedthe distribution of tidal volume and recruitment in pa-tients with ARDS using CT scans. They concluded thatPEEP makes the gas distribution more homogenous inpatients with ARDS, stretching the upper levels andrecruiting the lower ones, and thereby reduces the at-electatic tissue in dependent regions. Rouby173 has as-sessed PEEP-induced lung overdistension using CT.Rouby determined the threshold to differentiate PEEP-induced alveolar recruitment from PEEP-induced lungoverdistension. The threshold of 900 Hounsfield unitsallows a reliable determination of PEEP-induced alveolaroverdistension. A number of human studies have clearlyreported the simultaneous onset of alveolar recruitmentand lung overinflation in patients receiving PEEP levelsof 10 and 20 cm H2O.

174177 These recent approacheshave important implications in the diagnosis as well asthe management of atelectasis because they point clearlyto the propensity for injurious regional overinflationoccurring as a result of efforts to reverse atelectasis (e.g.,increased PEEP, recruitment maneuvers) in the setting ofARDS.Magnetic Resonance Imaging. Magnetic resonance

imaging allows three-dimensional imaging without the



use of ionizing radiation. Unfortunately, the lung is notwell suited to magnetic resonance imaging. On spin-echo images in healthy subjects, little signal is obtainedfrom lung parenchyma. Areas of consolidation andmasses can be identified, but the degree to which theycan be differentiated has yet to be fully established. Thistechnique has been used in preterm neonates to studypulmonary dysfunction.178 The authors compared lungwater content and distribution between preterm andterm infants and concluded that lung water content ishigher in preterm infants, consistent with dependentatelectasis.178 Xenon-enhanced CT is a method for non-invasive measurement of regional pulmonary ventilation,determined from the wash-in and wash-out rates of theradiodense, nonradioactive xenon gas, measured by se-rial CT scans.179 This may provide a valuable tool fornoninvasive measurement of regional lung function andatelectasis in the future. Although magnetic resonancehas several advantages over CT (e.g., contrast material isnot necessary, possibility for multiple planar imaging), itis not apparent that magnetic resonance offers any dis-tinct advantages over CT in the evaluation of atelectasisat the current time.180

Ultrasonography. Although more commonly used inassessment of pleural collections or in the context ofechocardiography, thoracic ultrasonography has beenused in assessment of lung parenchyma.181 It has beensuggested as a useful aid to the rapid diagnosis of atel-ectasis182 and, in the context of ARDS, seems to beuseful for the assessment of regional consolidation.183

Recently, use of a specific ultrasonographic detection ofthe cardiac impulse, termed the lung pulse, has beenreported to be a highly sensitive early indicator of thepresence of atelectasis.184 The use of ultrasonographymay offer significant advantages for patients in the op-erating room or in the intensive care unit in terms ofrapidity and ease of examination, without the disadvan-tages of patient transport and radiation exposure. How-ever, its role in clinical practice remains to bedetermined.185

Intravital Microscopy. Intravital microscopy appliedto the pleural surface enables experimental visualizationof atelectasis and examination of its role in the patho-genesis of lung injury (see Direct Visualization of Atelec-tasis).31 In addition to access issues, there are limitationsto interpretation,32 including the fact that visualization isrestricted to lung tissue that is immediately below thepleural surface, with deeper parenchyma beyond therange of the instrument.Cytokine Profile. There are other methods of detect-

ing atelectasis in the preclinical setting, including lunglavage levels of cytokines.125 Tremblay et al.125 exam-ined the effect of ventilation strategy on lung inflamma-tory mediators in the presence and absence of lunginjury using an isolated rat model. Lung lavage cytokineconcentrations were greatest in the groups ventilated

without PEEP in both the control intravenous lipopo-lysaccharidetreated groups. Zero PEEP in combinationwith high volume ventilation had a synergistic effect oncytokine concentrations. This finding that atelectasisworsens stretch-induced lung injury resulting in in-creased lung and systemic cytokine concentrations wasconfirmed by Chiumello et al.126 However, it is impor-tant to note that experimental atelectasiseven whenlethalis not associated with increased cytokines in theabsence of high tidal volumes.126 The measurement oflung lavage levels of cytokines in the clinical situation isimpractical.

Prevention or Reversal of AtelectasisThe factors important in the prevention or reversal of

atelectasis differ considerably, depending on whetherthe lungs are injured or uninjured. Because of the ad-verse pathophysiology associated with the developmentof atelectasis and the preclinical findings that recruit-ment of atelectatic lung may reduce the propensity to-ward subsequent injury,161163 it is important to exam-ine how recruitment may be achieved.Prevention or Reversal of Atelectasis in Healthy

Lungs. Progressive pulmonary atelectasis (and the asso-ciated impairment of oxygenation) may occur duringconstant ventilation whenever periodic hyperinflation islacking; it is reversible by passive hyperinflation (i.e.,three successive inflations: first, with a pressure of 20 cmH2O for 10 s; second, with a pressure of 30 cm H2O for15 s; and third, with a pressure of 40 cm H2O sustainedfor 15 s).2 This was taken as evidence that atelectaticalveoli are reopened by the deep breaths, and that con-clusion was supported by the reduction in pulmonarycompliance occurring during ventilation and the returnof compliance to control values after hyperinflation.

Nunn et al.107 examined arterial oxygenation in pa-tients during routine anesthesia. They found that arterialoxygenation increased when a pressure of 40 cm H2Owas maintained for 40 s; lower pressures, even withmodest levels of PEEP, were not effective.107 A morerecent study by Tusman et al.28 examined an alveolarrecruitment strategy in healthy lungs during generalanesthesia. The authors hypothesized that because atel-ectasis occurs during general anesthesia, an initial in-crease in pressure would be required to open collapsedalveoli, and if this inspiratory recruitment was combinedwith sufficient end-expiratory pressure, alveoli wouldremain open. They allocated patients to one of threegroups: no PEEP; an initial control period without PEEPfollowed by PEEP of 5 cm H2O; and PEEP of 15 cm H2Owith high tidal volume (18 ml/kg, or peak inspiratorypressure 40 cm H2O) maintained for 10 breaths, fol-lowed by stepwise reduction of PEEP and tidal volume.The third group, receiving the alveolar recruitment strat-egy, had a significant increase in arterial oxygenationduring general anesthesia. Treatment with PEEP of 5 cm



H2O alone did not have the same effect on oxygenation.The authors concluded that high initial pressures areneeded to overcome the anesthesia-induced collapse andthat PEEP of 5 cm or more is required to prevent thenewly recruited alveoli from collapsing. In addition,there was no evidence of barotrauma or pulmonarycomplications as a result of the high initial airwaypressures.28

Prevention or Reversal of Atelectasis in InjuredLungs. It has become evident that a number of ventila-tory strategies can produce or worsen lung injury.157

The use of large tidal volumes,153 high peak airwaypressures,186 and end-expiratory alveolar collapse withcyclic reopening120 have all been proposed as deleteri-ous when ventilating injured lungs. Several studies haveshown that lung injury secondary to ventilation withlarge tidal volume is attenuated if end-expiratory volumeis maintained by the use of PEEP.118,126,152 In addition,ventilation at low FRC worsens lung injury, possibly byrepeated small airway closure, and PEEP markedly atten-uates this injury.120,126 Therefore, recruitment of atelec-tatic lung reduces the injurious effects of mechanicalventilation with both low and high tidal volumes andprotects against development of ventilator-induced lunginjury.

The open-lung approach to ventilating patients withARDS consists of a recruitment maneuver with highsustained airway pressures to open atelectatic alveolifollowed by application of PEEP to maintain alveolarpatency. This approach was among the interventionsperformed in a study that showed an improvement inoxygenation and reduced mortality in patients withARDS.159 The researchers calculated the inflection pointfrom a pressurevolume curve (corresponding to anupward shift in the slope of the curve), and PEEP waspreset at 2 cm H2O above the inflection point in theprotective ventilation group. If the inflection point couldnot be determined on the pressurevolume curve, PEEPof 16 cm H2O was used. Recruiting maneuvers werefrequently used and consisted of continuous positiveairway pressures of 3540 cm H2O for 40 s followed bya return to previous PEEP levels.159

Gattinoni et al.40 also showed that with increasingPEEP from 0 to 20 cm H2O, gas distribution becamemore homogenous in sedated and paralyzed patientswith ARDS and reduced the reopeningcollapsing tis-sue. Suter et al.187 suggested that the optimum end-expiratory pressure in patients with acute respiratoryfailure was the PEEP level that resulted in the greatesttotal static compliance. This maximum compliance pro-duced by PEEP resulted in optimum overall cardiopul-monary interaction to ensure maximal global oxygendelivery. In patients with low FRC values at zero end-expiratory pressure, maximum oxygen transport wasachieved at higher levels of PEEP than in patients withnormal or high FRC values.

The timing of recruitment maneuvers was examinedby Grasso et al.188 in patients with ARDS who wereventilated with a lung-protective ventilatory strategy(low tidal volumes of 6 ml/kg). They defined a recruitingmaneuver as continuous positive airway pressure of40 cm H2O for 40 s. Measurements of PaO2/FIO2 ratio,volumepressure curve, and respiratory mechanics wereobtained 2 and 20 min after application of a recruitingmaneuver. The authors classified the patients as respond-ers and nonresponders. Recruitment maneuvers in-creased the PaO2/FIO2 ratio significantly more in respond-erswho had been ventilated for a longer period oftimethan in nonresponders. The authors concludedthat application of recruiting maneuvers improves oxy-genation only in patients with early ARDS who do nothave impairment of chest wall mechanics and with alarge potential for recruitment.188

Treating Atelectasis in the Postoperative Period.Postoperative pulmonary complications are increasinglyrecognized as an important perianesthetic issue.146 De-termination of the frequency and clinical impact of post-operative pulmonary complications is hampered by thelack of a uniform definition of a postoperative pulmo-nary complication among studies. Included in the defi-nition are pneumonia, severe respiratory failure (usuallydefined as the need for mechanical ventilation), bron-chospasm, and atelectasis (often not defined). Most stud-ies referring to postoperative atelectasis do not directlymeasure FRC.

Reversing or preventing atelectasis is possible in manypatients in the perioperative period146,189 and is ofproven benefit in preventing pulmonary complica-tions.146 Techniques or devices that either encourage orforce patients to inspire deeply are of most clinicalimportance.190192 The aim is to produce a large andsustained increase in transpulmonary pressure distend-ing the lung and reexpanding collapsed lung units. Sev-eral methods have been studied, including intermittentpositive-pressure breathing, deep-breathing exercises,incentive spirometry, and chest physiotherapy. A meta-analysis suggests that all regimens studied are equallyefficacious in reducing the frequency of postoperativepulmonary complications after upper abdominalsurgery.193

The beneficial effect on gas exchange of a simpleposture change from supine to seated has been demon-strated, both in healthy subjects90 and after upper ab-dominal surgery.91 Identification of FRC as the singlemost important lung volume in postoperative patientsprovides a specific goal of therapy.189 FRC can be mea-sured by a number of techniques. Gas dilution tech-niques (e.g., helium equilibration, nitrogen washout)have been used.93,194 One disadvantage of these meth-ods is that the tracer gas may not mix with all gas in thelungs because of occluded airways; this source of errorcan be overcome by using body plethysmography.



Finally, early work reported the use of thoracic orsternal traction195,196 as well as the use of intravenousaminophylline197 as successful treatments of atelectasisin a number of case reports, but given the impracticali-ties and adverse effects of these therapies, they have noclinical application today.Recruitment of Atelectatic Lung Is Easier to

Achieve in the Absence of Injury. Although the pres-surevolume relation in ARDSand the ability to recruitlungmay depend on the etiology,171 it is always easierto recruit lung when injury is absent or mild, comparedwith when significant injury is established.42,188,198 Thisis because the uninjured lung is highly compliant, and itsinflection point (opening pressure) on the inflation pres-surevolume curve is either low or not detectable. Incontrast, the inflection point is significantly greaterwhen injury has been established; in fact, elevation ofthe inflection point increases in proportion to the extentof injury.194 Such impaired compliance (and difficultywith recruitment) has a pathophysiologic basis in estab-lished injury. The causes include surfactant dysfunctiondue to impairment of large aggregate formation,199 di-rect inhibition by plasma proteins that have exudatedinto the air space,200202 and the progression of cellularinfiltration and edema in the pulmonary interstitium andalveoli.203,204 Increases in pulmonary vascular resis-tance, which characteristically parallel the progressionof the lung injury,205 may decrease lung compliancefurther.206 Finally, when recruitment has been achieved,less airway pressure is required to prevent derecruit-ment than is required to achieve recruitment.207

Summary and Future Implications

In the future, clinicians may be able to predict thesubsequent development of ALI. In an optimal setting,this would be after recognition of the identifiable etiol-ogy and before its initiation (e.g., before major surgery orbefore reperfusion during transplantation surgery). Alter-natively, early institution of prophylactic recruitmentafter identification of an etiologic event, particularlywhen associated with a worrisome predictive stratifica-tion (e.g., pancreatitis with elevated cytokine profile),would be ideal. The eventual prospect of predicting (orearly detection of) ALI and ARDS makes prophylacticlung recruitment (to maintain or recover normal restinglung volume) increasingly tenable, and if validated byclinical studies, this could become integrated into theperioperative care of patients who are at risk of devel-oping critical illness.

Atelectasis occurs in almost all patients undergoinggeneral anesthesia. We have reviewed the causes, ef-fects, nature, identification, and prevention of atelectasisin the perioperative period. Unless restoration of FRCtakes place, atelectasis can have detrimental conse-

quences. Current literature indicates that intraoperativeand postoperative lung recruitment improves intermedi-ate physiologic outcomes (e.g., oxygenation, work ofbreathing); however, the benefits might have more sig-nificant implications for lung injury and ARDS. Lowstretch ventilation can achieve, at best, attenuation ofstretch-induced injury; at worst, it can cause loss of lungvolume, potentially contributing to or worsening injury.Prophylactic recruitment however, could reduce or pre-vent lung injury that results from a variety of primaryetiologies, as well as reducing injury resulting from me-chanical stretch. If proven in the clinical setting, thisapproach could reduce the development of critical ill-ness in many general medical and surgical patientpopulations.

Note Added in Proof

Since acceptance of this manuscript, Squadrone et al.have demonstrated that reversing atelectasis with non-invasive continuous positive airway pressure in high-riskpostoperative patients who are hypoxic results in re-duced need for reintubation and a lower incidence ofpneumonia and sepsis (Squadrone V, Coha M, Cerutti E,Schellino MM, Biolino P, Occella P, Belloni G, Vilianis G,Fiore G, Cavallo F, Ranieri VM; Piedmont Intensive CareUnits Network [PICUN]: Continuous positive airwaypressure for treatment of postoperative hypoxemia: Arandomized controlled trial. JAMA 2005; 293:58995).

The authors thank Steven Deem, M.D. (Associate Professor, Departments ofAnesthesiology and Medicine, University of Washington, Seattle, Washington),Rolf Hubmayr, M.D. (Professor, Department of Medicine, Mayo Clinic, Rochester,Minnesota), and John Laffey, M.D. (Consultant Anesthetist, University Hospitaland National University of Ireland, Galway, Ireland), for their expert commentson the manuscript; and Theresa Sakno (Sakno Media, Toronto, Ontario, Canada)for the artwork.

References

1. Nunn JF, Payne JP: Hypoxaemia after general anaesthesia. Lancet 1962;2:6312

2. Bendixen HH, Hedley-Whyte J, Chir B, Laver MB: Impaired oxygenation insurgical patients during general anesthesia with controlled ventilation. N EnglJ Med 1963; 269:9916

3. Lundquist H, Hedenstierna G, Strandberg A, Tokics L, Brismar B: CT-assessment of dependent lung densities in man during general anaesthesia. ActaRadiol 1995; 36:62632

4. Hedenstierna G, Rothen HU: Ventilation and perfusion matching, Anesthe-sia Biologic Foundations. Edited by Yaksh TL, Lynch CL, Zapol WM, Maze M,Biebuyck JF, Saidman LJ. Philadelphia, LippincottRaven, 1998, pp 134966

5. Brismar B, Hedenstierna G, Lundquist H, Strandberg A, Svensson L, TokicsL: Pulmonary densities during anesthesia with muscular relaxation: A proposal ofatelectasis. ANESTHESIOLOGY 1985; 62:4228

6. Froese AB, Bryan AC: Effects of anesthesia and paralysis on diaphragmaticmechanics in man. ANESTHESIOLOGY 1974; 41:24255

7. Nunn JF: Nunns Applied Respiratory Physiology, 3rd edition. London,Butterworth Heinemann, 1987, pp 35070

8. Hedenstierna G, Strandberg A, Brismar B, Lundquist H, Svensson L, TokicsL: Functional residual capacity, thoracoabdominal dimensions, and central bloodvolume during general anesthesia with muscle paralysis and mechanical ventila-tion. ANESTHESIOLOGY 1985; 62:24754

9. Krayer S, Rehder K, Beck KC, Cameron PD, Didier EP, Hoffman EA: Quan-tification of thoracic volumes by three-dimensional imaging. J Appl Physiol 1987;62:5918

10. Hubmayr RD, Rodarte JR, Walters BJ, Tonelli FM: Regional ventilation



during spontaneous breathing and mechanical ventilation in dogs. J Appl Physiol1987; 63:246775

11. Benameur M, Goldman MD, Ecoffey C, Gaultier C: Ventilation and thora-coabdominal asynchrony during halothane anesthesia in infants. J Appl Physiol1993; 74:15916

12. Hedenstierna G, Tokics L, Lundquist H, Andersson T, Strandberg A, Bris-mar B: Phrenic nerve stimulation during halothane anesthesia: Effects of atelec-tasis. ANESTHESIOLOGY 1994; 80:75160

13. Loring SH, Butler JP: Gas exchange in body cavities, Handbook of Physi-ology. Section 3, The Respiratory System. Vol 4, Gas Exchange. Edited by FarhiLE, Tenney SM. Bethesda, American Physiological Society, 1987, pp 28395

14. Joyce CJ, Baker AB, Kennedy RR: Gas uptake from an unventilated area oflung: Computer model of absorption atelectasis. J Appl Physiol 1993; 74:110716

15. Rehder K, Knopp TJ, Sessler AD, Didier EP: Ventilation-perfusion relation-ship in young healthy awake and anesthetized-paralyzed man. J Appl Physiol1979; 47:74553

16. Wagner PD, Laravuso RB, Uhl RR, West JB: Continuous distributions ofventilation-perfusion ratios in normal subjects breathing air and 100 per cent O2.J Clin Invest 1974; 54:5468

17. Woo SW, Berlin D, Hedley-Whyte J: Surfactant function and anestheticagents. J Appl Physiol 1969; 26:5717

18. Wollmer P, Schairer W, Bos JA, Bakker W, Krenning EP, Lachmann B:Pulmonary clearance of 99mTc-DTPA during halothane anaesthesia. Acta Anaes-thesiol Scand 1990; 34:5725

19. Nicholas TE, Barr HA: The release of surfactant in rat lung by brief periodsof hyperventilation. Respir Physiol 1983; 52:6983

20. Hildebran JN, Goerke J, Clements JA: Surfactant release in excised rat lungis stimulated by air inflation. J Appl Physiol 1981; 51:90510

21. Oyarzun MJ, Clements JA: Ventilatory and cholinergic control of pulmo-nary surfactant in the rabbit. J Appl Physiol 1977; 43:3945

22. Oyarzun MJ, Clements JA: Control of lung surfactant by ventilation, adren-ergic mediators, and prostaglandins in the rabbit. Am Rev Respir Dis 1978;117:87991

23. Oyarzun MJ, Iturriaga R, Donoso P, Dussaubat N, Santos M, SchiappacasseME, Lathrop ME, Larrain C, Zapata P: Factors affecting distribution of alveolarsurfactant during resting ventilation. Am J Physiol 1991; 261:L2107

24. Magnusson L, Spahn DR: New concepts of atelectasis during generalanaesthesia. Br J Anaesth 2003; 91:6172

25. Strandberg A, Hedenstierna G, Tokics L, Lundquist H, Brismar B: Densitiesin dependent lung regions during anaesthesia: Atelectasis or fluid accumulation?Acta Anaesthesiol Scand 1986; 30:2569

26. Hedenstierna G, Lundquist H, Lundh B, Tokics L, Strandberg A, Brismar B,Frostell C: Pulmonary densities during anaesthesia: An experimental study onlung morphology and gas exchange. Eur Respir J 1989; 2:52835

27. Tusman G, Bohm SH, Vazquez de Anda GF, do Campo JL, Lachmann B:Alveolar recruitment strategy improves arterial oxygenation during generalanaesthesia. Br J Anaesth 1999; 82:813

28. Tusman G, Bohm SH, Tempra A, Melkun F, Garcia E, Turchetto E, MulderPG, Lachmann B: Effects of recruitment maneuver on atelectasis in anesthetizedchildren. ANESTHESIOLOGY 2003; 98:1422

29. Rothen HU, Sporre B, Engberg G, Wegenius G, Hedenstierna G: Re-expansion of atelectasis during general anaesthesia: A computed tomographystudy. Br J Anaesth 1993; 71:78895

30. Rothen HU, Sporre B, Engberg G, Wegenius G, Hedenstierna G: Reexpan-sion of atelectasis during general anaesthesia may have a prolonged effect. ActaAnaesthesiol Scand 1995; 39:11825

31. Halter JM, Steinberg JM, Schiller HJ, DaSilva M, Gatto LA, Landas S, NiemanGF: Positive end-expiratory pressure after a recruitment maneuver prevents bothalveolar collapse and recruitment/derecruitment. Am J Respir Crit Care Med2003; 167:16206

32. Kavanagh BP: Lung recruitment in real time: Learning was never so easy.Am J Respir Crit Care Med 2003; 167:15856

33. West JB: Respiratory Physiology, 5th edition. Baltimore, Williams & Wil-liams, 1995, pp 5169

34. Baumgardner JE, Markstaller K, Pfeiffer B, Doebrich M, Otto CM: Effects ofrespiratory rate, plateau pressure, and positive end-expiratory pressure on PaO2oscillations after saline lavage. Am J Respir Crit Care Med 2002; 166:155662

35. Williams EM, Viale JP, Hamilton RM, McPeak H, Sutton L, Hahn CE:Within-breath arterial PO2 oscillations in an experimental model of acute respi-ratory distress syndrome. Br J Anaesth 2000; 85:4569

36. Ludwigs U, Klingstedt C, Baehrendtz S, Wegenius G, Hedenstierna G:Volume-controlled inverse ratio ventilation in oleic acid induced lung injury:Effects on gas exchange, hemodynamics, and computed tomographic lung den-sity. Chest 1995; 108:8049

37. Mang H, Kacmarek RM, Ritz R, Wilson RS, Kimball WP: Cardiorespiratoryeffects of volume- and pressure-controlled ventilation at various I/E ratios in anacute lung injury model. Am J Respir Crit Care Med 1995; 151:7316

38. Neumann P, Berglund JE, Mondejar EF, Magnusson A, Hedenstierna G:Effect of different pressure levels on the dynamics of lung collapse and recruit-ment in oleic-acid-induced lung injury. Am J Respir Crit Care Med 1998; 158:163643

39. Hubmayr RD: Perspective on lung injury and recruitment: A skeptical lookat the opening and collapse story. Am J Respir Crit Care Med 2002; 165:164753

40. Gattinoni L, Pelosi P, Crotti S, Valenza F: Effects of positive end-expiratorypressure on regional distribution of tidal volume and recruitment in adult respi-ratory distress syndrome. Am J Respir Crit Care Med 1995; 151:180714

41. Gattinoni L, DAndrea L, Pelosi P, Vitale G, Pesenti A, Fumagalli R: Regionaleffects and mechanism of positive end-expiratory pressure in early adult respi-ratory distress syndrome. JAMA 1993; 269:21227

42. Gattinoni L, Pesenti A, Avalli L, Rossi F, Bombino M: Pressure-volumecurve of total respiratory system in acute respiratory failure: Computed tomo-graphic scan study. Am Rev Respir Dis 1987; 136:7306

43. Hubmayr RD, Walters BJ, Chevalier PA, Rodarte JR, Olson LE: Topograph-ical distribution of regional lung volume in anesthetized dogs. J Appl Physiol1983; 54:104856

44. Agostoni E, DAngelo E, Bonanni MV: The effect of the abdomen on thevertical gradient of pleural surface pressure. Respir Physiol 1970; 8:33246

45. DAngelo E, Bonanni MV, Michelini S, Agostoni E: Topography of thepleural pressure in rabbits and dogs. Respir Physiol 1970; 8:20429

46. Martynowicz MA, Minor TA, Walters BJ, Hubmayr RD: Regional expansionof oleic acid-injured lungs. Am J Respir Crit Care Med 1999; 160:2508

47. Hedenstierna G, Jarnberg PO, Gottlieb I: Thoracic gas volume measured bybody plethysmography during anesthesia and muscle paralysis: Description andvalidation of a method. ANESTHESIOLOGY 1981; 55:43943

48. Strandberg A, Tokics L, Brismar B, Lundquist H, Hedenstierna G: Atelec-tasis during anaesthesia and in the postoperative period. Acta Anaesthesiol Scand1986; 30:1548

49. Westbrook PR, Stubbs SE, Sessler AD, Rehder K, Hyatt RE: Effects ofanesthesia and muscle paralysis on respiratory mechanics in normal man. J ApplPhysiol 1973; 34:816

50. Tokics L, Hedenstierna G, Strandberg A, Brismar B, Lundquist H: Lungcollapse and gas exchange during general anesthesia: Effects of spontaneousbreathing, muscle paralysis, and positive end-expiratory pressure. ANESTHESIOLOGY1987; 66:15767

51. Freund FG, Bonica JJ, Ward RJ, Akamatsu TJ, Kennedy WF Jr: Ventilatoryreserve and level of motor block during high spinal and epidural anesthesia.ANESTHESIOLOGY 1967; 28:8347

52. Ward RJ, Bonica JJ, Freund FG, Akamatsu T, Danziger F, Englesson S:Epidural and subarachnoid anesthesia: Cardiovascular and respiratory effects.JAMA 1965; 191:2758

53. Yamakage M, Namiki A, Tsuchida H, Iwasaki H: Changes in ventilatorypattern and arterial oxygen saturation during spinal anaesthesia in man. ActaAnaesthesiol Scand 1992; 36:56971

54. McCarthy GS: The effect of thoracic extradural analgesia on pulmonary gasdistribution, functional residual capacity and airway closure. Br J Anaesth 1976;48:2438

55. Don HF, Wahba M, Cuadrado L, Kelkar K: The effects of anesthesia and100 per cent oxygen on the functional residual capacity of the lungs. ANESTHESI-OLOGY 1970; 32:5219

56. Don HF, Wahba WM, Craig DB: Airway closure, gas trapping, and thefunctional residual capacity during anesthesia. ANESTHESIOLOGY 1972; 36:5339

57. Lundh R, Hedenstierna G: Ventilation-perfusion relationships during an-aesthesia and abdominal surgery. Acta Anaesthesiol Scand 1983; 27:16773

58. Jonmarker C, Nordstrom L, Werner O: Changes in functional residualcapacity during cardiac surgery. Br J Anaesth 1986; 58:42832

59. Slocum HC, Hoeflich EA, Allen CR: Circulatory and respiratory distressfrom extreme positions on the operating table. Surg Gynecol Obstet 1947;84:10657

60. Rehder K, Hatch DJ, Sessler AD, Fowler WS: The function of each lung ofanesthetized and paralyzed man during mechanical ventilation. ANESTHESIOLOGY1972; 37:1626

61. Lumb AB, Nunn JF: Respiratory function and ribcage contribution toventilation in body positions commonly used during anesthesia. Anesth Analg1991; 73:4226

62. Rehder K, Knopp TJ, Sessler AD: Regional intrapulmonary gas distributionin awake and anesthetized-paralyzed prone man. J Appl Physiol 1978; 45:52835

63. Gattinoni L, Tognoni G, Pesenti A, Taccone P, Mascheroni D, Labarta V,Malacrida R, Di Giulio P, Fumagalli R, Pelosi P, Brazzi L, Latini R: Effect of pronepositioning on the survival of patients with acute respiratory failure. N Engl J Med2001; 345:56873

64. Broccard AF, Shapiro RS, Schmitz LL, Ravenscraft SA, Marini JJ: Influenceof prone position on the extent and distribution of lung injury in a high tidalvolume oleic acid model of acute respiratory distress syndrome. Crit Care Med1997; 25:1627

65. Broccard A, Shapiro RS, Schmitz LL, Adams AB, Nahum A, Marini JJ: Pronepositioning attenuates and redistributes ventilator-induced lung injury in dogs.Crit Care Med 2000; 28:295303

66. Magnusson L, Zemgulis V, Wicky S, Tyden H, Thelin S, Hedenstierna G:Atelectasis is a major cause of hypoxemia and shunt after cardiopulmonarybypass: An experimental study. ANESTHESIOLOGY 1997; 87:115363

67. Tenling A, Hachenberg T, Tyden H, Wegenius G, Hedenstierna G: Atelec-tasis and gas exchange after cardiac surgery. ANESTHESIOLOGY 1998; 89:3718

68. Macnaughton PD, Braude S, Hunter DN, Denison DM, Evans TW: Changesin lung function and pulmonary capillary permeability after cardiopulmonarybypass. Crit Care Med 1992; 20:128994

69. Claxton BA, Morgan P, McKeague H, Mulpur A, Berridge J: Alveolar



recruitment strategy improves arterial oxygenation after cardiopulmonary by-pass. Anaesthesia 2003; 58:1116

70. Dyhr T, Laursen N, Larsson A: Effects of lung recruitment maneuver andpositive end-expiratory pressure on lung volume, respiratory mechanics andalveolar gas mixing in patients ventilated after cardiac surgery. Acta AnaesthesiolScand 2002; 46:71725

71. Loeckinger A, Kleinsasser A, Lindner KH, Margreiter J, Keller C, HoermannC: Continuous positive airway pressure at 10 cm H2O during cardiopulmonarybypass improves postoperative gas exchange. Anesth Analg 2000; 91:5227

72. Benumof JL: Preoxygenation: Best method for both efficacy and efficiency.ANESTHESIOLOGY 1999; 91:6035

73. Krayer S, Rehder K, Beck KC, Cameron PD, Didier EP, Hoffman EA:Quantification of thoracic volumes by three-dimensional imaging. J Appl Physiol1987; 62:5918

74. Reber A, Engberg G, Wegenius G, Hedenstierna G: Lung aeration: Theeffect of pre-oxygenation and hyperoxygenation during total intravenous anaes-thesia. Anaesthesia 1996; 51:7337

75. Rothen HU, Sporre B, Engberg G, Wegenius G, Reber A, Hedenstierna G:Prevention of atelectasis during general anaesthesia. Lancet 1995; 345:138791

76. Benoit Z, Wicky S, Fischer JF, Frascarolo P, Chapuis C, Spahn DR, Mag-nusson L: The effect of increased FIO2 before tracheal extubation on postoper-ative atelectasis. Anesth Analg 2002; 95:177781

77. Preoxygenation: Physiology and practice. Lancet 1992; 339:31278. Edmark L, Kostova-Aherdan K, Enlund M, Hedenstierna G: Optimal oxygen

concentration during induction of general anesthesia. ANESTHESIOLOGY 2003; 98:2833

79. Greif R, Akca O, Horn EP, Kurz A, Sessler DI: Supplemental perioperativeoxygen to reduce the incidence of surgical-wound infection. Outcomes ResearchGroup. N Engl J Med 2000; 342:1617

80. Sessler DI, Akca O: Nonpharmacological prevention of surgical woundinfections. Clin Infect Dis 2002; 35:1397404

81. Greif R, Laciny S, Rapf B, Hickle RS, Sessler DI: Supplemental oxygenreduces the incidence of postoperative nausea and vomiting. ANESTHESIOLOGY1999; 91:124652

82. Purhonen S, Turunen M, Ruohoaho UM, Niskanen M, Hynynen M: Sup-plemental oxygen does not reduce the incidence of postoperative nausea andvomiting after ambulatory gynecologic laparoscopy. Anesth Analg 2003; 96:916

83. Jensen AG, Kalman SH, Eintrei C, Fransson SG, Morales O: Atelectasis andoxygenation in major surgery with either propofol with or without nitrous oxideor isoflurane anaesthesia. Anaesthesia 1993; 48:10946

84. Joyce CJ, Baker AB: Effects of inspired gas composition during anaesthesiafor abdominal hysterectomy on postoperative lung volumes. Br J Anaesth 1995;75:41721

85. Gunnarsson L, Strandberg A, Brismar B, Tokics L, Lundquist H, Hedensti-erna G: Atelectasis and gas exchange impairment during enflurane/nitrous oxideanaesthesia. Acta Anaesthesiol Scand 1989; 33:62937

86. Gunnarsson L, Tokics L, Gustavsson H, Hedenstierna G: Influence of ageon atelectasis formation and gas exchange impairment during general anaesthe-sia. Br J Anaesth 1991; 66:42332

87. Serafini G, Cornara G, Cavalloro F, Mori A, Dore R, Marraro G, Braschi A:Pulmonary atelectasis during paediatric anaesthesia: CT scan evaluation andeffect of positive endexpiratory pressure (PEEP). Paediatr Anaesth 1999; 9:2258

88. Davis GM, Coates AL, Papageorgiou A, Bureau MA: Direct measurement ofstatic chest wall compliance in animal and human neonates. J Appl Physiol 1988;65:10938

89. Keens TG, Bryan AC, Levison H, Ianuzzo CD: Developmental pattern ofmuscle fiber types in human ventilatory muscles. J Appl Physiol 1978; 44:90913

90. Craig DB, Wahba WM, Don HF, Couture JG, Becklake MR: Closingvolume and its relationship to gas exchange in seated and supine positions.J Appl Physiol 1971; 31:71721

91. Vaughan RW, Wise L: Intraoperative arterial oxygenation in obese pa-tients. Ann Surg 1976; 184:3542

92. Hedenstierna G, Santesson J: Breathing mechanics, dead space and gasexchange in the extremely obese, breathing spontaneously and during anaesthe-sia with intermittent positive pressure ventilation. Acta Anaesthesiol Scand 1976;20:24854

93. Pelosi P, Croci M, Ravagnan I, Tredici S, Pedoto A, Lissoni A, Gattinoni L:The effects of body mass on lung volumes, respiratory mechanics, and gasexchange during general anesthesia. Anesth Analg 1998; 87:65460

94. Shnider SM, Levinson G: Anesthesia for obstetrics, Anesthesia. Edited byMiller RD. New York, Churchill Livingstone, 1994, pp 203176

95. The Acute Respiratory Distress Syndrome Network: Ventilation with lowertidal volumes as compared with traditional tidal volumes for acute lung injury andthe acute respiratory distress syndrome. N Engl J Med 2000; 342:13018

96. Ranieri VM, Suter PM

20051129 atelectasis

Documents