Acute lunginjurycuropinanaesthesiol

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Acute lung injury and outcomes
after thoracic surgeryMarc Lickera, Pascal Fauconneta, Yann Villigera and Jean-Marie Tschoppb
aDepartment of Anaesthesiology, Pharmacology andIntensive Care, rue Micheli-du-Crest, UniversityHospital of Geneva, Geneva and bDepartment ofInternal Medicine, Chest Medical Centre, Montana,Switzerland

Correspondence to Marc Licker, MD, Serviced’Anesthesiologie, Hopitaux Universitaires de Geneve,Rue Micheli-du-Crest, CH-1211 Geneva, SwitzerlandTel: +41 22 3827439; fax: +41 22 3827403;e-mail: [email protected]

Current Opinion in Anaesthesiology 2009,22:61–67

Purpose of review

The present review evaluates the evidence available in the literature tracking

perioperative mortality and morbidity as well as the pathogenesis and management of

acute lung injury (ALI) in patients undergoing thoracotomy.

Recent findings

Over the last decade, despite increasing age and comorbid conditions, the operative

mortality has remained unchanged for patients undergoing lung resection, whereas

procedure-related complications have declined. Better clinical outcomes are achieved

in high-volume hospitals and when procedures are performed by a thoracic surgeon.

Postthoracotomy ALI has become the leading cause of operative death, its incidence

has remained stable (2–5%) and earlier diagnosis can be made by assessing the

extravascular lung water volume with the single-indicator dilution technique. The

pathogenesis of ALI implicates a multiple-hit sequence of various triggering factors (e.g.

oxidative stress and surgical-induced inflammation) in addition to injurious ventilatory

settings and genetic predisposition.

Summary

Knowledge of the perioperative risk factors of major complications and understanding of

the mechanisms of postthoracotomy ALI enable anesthesiologists to implement

‘protective’ lung strategies including the use of low tidal volume (VT) with recruitment

maneuvers, a goal-directed fluid approach and prophylactic treatment with inhaled

b2-adrenergic agonists.

Keywords

acute lung injury, lung resection, mechanical ventilation, thoracotomy, tidal volume

Curr Opin Anaesthesiol 22:61–67� 2009 Wolters Kluwer Health | Lippincott Williams & Wilkins0952-7907

IntroductionThoracotomies with lung resection are classified as inter-

mediate-to-major surgical procedures with in-hospital

mortality rates expected to be less than 2% for lobectomy

and less than 6% for pneumonectomy [1,2�]. Among

512 578 thoracic procedures performed from 1988 to

2002 in the United States, several changes have been

identified: surgical candidates are more likely to be older

(mean age of 63 years), women (40%) and to undergo

lobectomy instead of pneumonectomy due to earlier

diagnosis of cancer stages [3]. Despite higher comorbid

status, operative mortality has remained unchanged and

the length of hospital stay has become shorter along with

a reduction of procedure-related complications. Nowa-

days, the main causes of mortality have shifted from

cardiac and surgical complications towards infectious

complications (pneumonia, empyema and sepsis) and

the acute lung injury (ALI) syndrome with its most

severe form the acute respiratory distress syndrome

(ARDS).

opyright © Lippincott Williams & Wilkins. Unauth

0952-7907 � 2009 Wolters Kluwer Health | Lippincott Williams & Wilkins

Risk factors of operative mortalityOutcomes following lung resection largely differ between

specialized and nonspecialized medical centres.

Mortality rates as low as 2.2% have been reported in a

French survey including 15 183 patients managed by

specialized thoracic teams, whereas fatality rates as high

as 12% have been observed in the US nationally repre-

sentative samples of Medicare patients aged over 65 years

[4,5]. Qualified cardiothoracic surgeons devoting their

practice entirely or mainly to thoracic surgery achieve

better results than nonspecialized surgeons [6]. Improved

short and long-term results are also achieved in hospitals

with a high volume of any complex procedure, emphasiz-

ing the key role of multidisciplinary teams, the avail-

ability of intensive care resources with an acute pain

service as well as the implementation of scientifically

evidence-based practices [7,8].

Apart from these organizational factors, analysis of the

European Thoracic Surgery Database and of the French

orized reproduction of this article is prohibited.

DOI:10.1097/ACO.0b013e32831b466c

mailto:[email protected]

http://dx.doi.org/10.1097/ACO.0b013e32831b466c

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62 Thoracic anaesthesia

Table 1 Overview of studies on the postthoracotomy acute lung injury syndrome

Reference n Risk factors

Incidence (%)

Mortality (%)Overall P L <L

Licker et al. [11] 879 MV, high Pinsp aw, fluid overload (first 24 h),pneumonectomy, alcohol abuse

4.2 8.4 3.1 3.4 37

Ruffini et al. [12] 1221 NA 2.2 3.8 2 3.2 52Kutlu et al. [13] 1139 Age>60 years, male sex, lung cancer, extended

resection3.9 6 3.7 1 64

Alam et al. [14] 1428 ppoFEV1, ppoDLC0, fluid overload (intraoperative) 3.1 10.1 5.5 4.1 25Dulu et al. [15] 2192 NA 2.5 7.9 3 0.9 40Fernandez-Perez [16] 170a High VT (8.3 vs. 6.7 ml/kg), fluid overload

(intraoperative)NA 8.8 40

van der Werff et al. [17] 197 MV, high Pinspir aw, fresh-frozen plasma 2.5 100Turnage et al. [18] 806 NA 2.6 100Verheijen-Breemhar et al. [19] 243 NA 4.5 27Waller et al. [20] 205 NA 4.4 56Algar et al. [21] 242a Operative time, ppoFEV1, prior cardiac disease,

COPD, no chest therapy (preoperative)2.5 2.5

Song et al. [22] 635 NA 3.6 48Katzenelson et al. [23] 146a Prior chemotherapy, prior chemotherapy, FEV1

<45% predicted, predicted postoperative lungperfusion<55%, fluid overload (intraoperative)

15 15

COPD, chronic obstructive pulmonary disease; <L, lesser resection than lobectomy; L, lobectomy; MV, mechanical ventilation; Pinspir aw, inspiratoryairway pressure; P, pneumonectomy; ppoDLCO, predicted postoperative diffusion lung capacity to carbon monoxide; ppoFEV1, predicted post-operative forced expiratory volume in 1 s; VT, tidal volume; NA, not applicable.a Only pneumonectomy cases.

national dataset have identified independent risk factors

of perioperative death: age, male sex, dyspnea score,

functional performance status, American Society of

Anesthesiologists (ASA) score and the extent of surgical

resection [4,9]. These models of risk have been validated

in second sets of population, with good predictive accu-

racies (c-index� 0.85).

Epidemiology and diagnostic criteria of acutelung injuryThe guidelines set out by the American–European

Consensus Conference on ARDS have been widely

adopted to describe postthoracotomy ALI, previously

coined postpneumonectomy pulmonary oedema, low-

pressure oedema or permeability pulmonary oedema.

Although the diagnosis of ALI/ARDS relies on specific

criteria [acute onset of hypoxemia, arterial oxygen pres-

sure (PaO2)/fraction of inspired oxygen (FIO2) less than

300 for ALI and less than 200 for ARDS, diffuse radio-

logical infiltrates and no evidence of elevated hydrostatic

capillary pressure], a wide spectrum of lung injuries is

encountered [10]. Importantly, two clinical patterns of

postthoracotomy ALI should be distinguished corre-

sponding to different pathogenic triggers: ALI develop-

ing within 48–72 h after lung resection (primary ALI) and

a delayed form triggered by postoperative complications

such as bronchoaspiration or pneumonia [11].

Contrasting with other cardiopulmonary complications,

the incidence of postthoracotomy ALI has not shown any

noticeable decrease over the last two decades (between 2

and 4%) although the case-fatality rate has decreased

opyright © Lippincott Williams & Wilkins. Unautho

from almost 100% to less than 40% owing to improved

ICU medical management (Table 1) [11–22].

New semiinvasive monitoring tools have appeared in the

perioperative arena providing valuable information for

early diagnosis of ALI and haemodynamic treatment.

The single-indicator thermal dilution method (Pulsion,

Munich, Germany) has been validated against the gravi-

metric method to assess the extravascular lung water

index (EVLWI) [23]. This simple technique has proven

sensitive to detect infraclinical variations in EVLWI, to

estimate a pulmonary vascular permeability index while

monitoring cardiac output using pulse contour analysis of

the arterial pressure [24]. Pulmonary artery catheters

have been replaced by ultrasound imaging for cardiocir-

culatory assessment. Chest ultrasound scans can also be

used to detect excess lung water content. ‘Comet-tail

images’ fanning out from the lung surface and originating

from water-thickened interlobular septa have been

shown to correlate closely with lung water content

[25,26].

Clinical risk factors and pathophysiology ofpostthoracotomy acute lung injurySeveral risk factors of the early form of postthoracotomy

ALI have been identified in cohorts of thoracic surgical

patients. Using multivariate regression analysis, the

strongest predictors of postthoracotomy ALI are related

to the preoperative condition of the patient (severe

pulmonary dysfunction and chronic alcohol consump-

tion) and to perioperative medical care (extended lung

resection, ‘injurious’ ventilation and fluid overhydration)

rized reproduction of this article is prohibited.

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ALI and outcomes after thoracic surgery Licker et al. 63

[11]. Moreover, the occurrence of ALI is more frequently

reported after right pneumonectomy in elderly patients

with colonized airways or in those requiring multiple

transfusions or receiving neoadjuvant chemoradiotherapy

[27–29].

Rather than a unified stereotyped response, a multiple-

hit sequence of deleterious events likely interacts

resulting in alveolar epithelial and capillary endothelial

injuries, with alterations in extracellular matrix (ECM),

ultimately leading to the characteristic histopathological

features of ALI [30].

The ‘neutrophil hypothesis’ suggests that circulating

neutrophils are activated by proinflammatory mediators

such as granulocyte and macrophage–colony stimulating

factors in concert with various chemokines. These neu-

trophils experience delayed apoptosis and sustained

release of proteolytic enzymes, reactive oxygen inter-

mediates/reactive nitrogen intermediates (ROIs/RNIs)

as well as proinflammatory mediators [31].

The ‘epithelial hypothesis’ emphasizes the role of both

lung parenchymal cell apoptosis and chemotactic/inflam-

matory responses, which are associated with increased

expression of Fas on epithelial cells, along with enhanced

extravasation of Fas ligand-expressing cells [32].

Ventilatory strategy

Recent experimental and clinical studies have empha-

sized the ‘injurious’ aspects of physical stress and hyper-

oxia associated with mechanical ventilation that may

trigger inflammatory changes at the alveolar–capillary

barrier in ‘vulnerable’ surgical patients as characterized

by genetic factors, disrupted lympathic vessels and pro-

inflammatory circulating mediators associated with pre-

existing lung disease or surgical trauma.

Basic science

Even ‘physiological’ low VT (4–8 ml/kg) delivered over

several hours in healthy lungs may produce subtle lung

injuries: neutrophil infiltration, rupture of alveolar–bron-

chial attachment and chondroitin–sulfate proteoglycan

fragmentation in the ECM [33]. With larger VT, there is

further macromolecular fragmentation, activation of

matrix metalloprotease and upregulation of collagen syn-

thesis in the ECM that represent an autoregulatory

response to maintain low pulmonary compliance while

protecting the ECM against fluid overload [34–36]. Inter-

estingly, induction of unilateral ventilator-induced injury

(VILI) in one lung with high VT does not trigger a

concomitant inflammatory response in the contralateral

normally ventilated lung [37].

Ventilation with large VT is not sufficient per se to induce

ALI in healthy lungs, as defense and repair mechanisms


[e.g. antioxidant, heat-shock protein, p75 receptor for

tumor necrosis factor (TNF)-a] counteract the initial

inflammatory and oxidative responses [38,39]. The in-

creased permeability of the alveolar–capillary barrier along

with a decreased lung compliance initially results from the

disruption of intercellular endothelial cell junction, cytos-

keleton contraction and alveolar cell death consequent

to activation of endothelial/epithelial cell receptors by

systemic/alveolar inflammatory mediators [e.g. thrombine,

vascular endothelial growth factor (VEGF), transforming

growth factor-beta (TGF-b) and thromboxane A2 (TxA2)]

[40–42].

Clinical studies

In the ICU setting, the benefits of a protective lung

ventilation (PLV) strategy have been clearly documented

in large observational studies and meta-analysis of random-

ized controlled trials (RCTs) [43]. In clinical practice, PLV

entails the delivery of low VT (less than 7 ml/kg) with

pressure-limited ventilation (less than 30 cm of H2O) and

the application of positive end-expiratory pressure (PEEP)

with periodic recruitment maneuvers [44��].

During short periods of mechanical ventilation (4–6 h),

atelectatic areas are common and so-called ‘low-volume’

injuries may result from repetitive opening and closing of

unstable lung units owing to inactivation of surfactant and

excessive mechanical stress between neighboring lung

areas [45,46].

Several RCTs including surgical patients with healthy

lungs have questioned whether different ventilatory set-

tings could modulate pulmonary/systemic inflammation

while influencing oxygenation index and respiratory

mechanical properties [47]. As summarized in Table 2

[48–59], no benefit could be demonstrated by varying the

VT for surgical procedures lasting less than 5 h [48,49]. In

contrast, in all studies, except one including more severe

surgical stresses (e.g. major operations exceeding 5 h and

cardiac surgery), intraoperative ventilation with lower VT

(5–6 ml/kg) and PEEP was associated with stable or

improved oxygenation, reduced expression of alveolar

and systemic inflammation and reduced procoagulant

activity in the bronchoalveolar lavage fluid (BALF) [50–

55]. In agreement with these data, Lee et al. [57] reported a

trend for lower incidence in pulmonary complications and

for shorter intubation periods in patients ventilated with

small VT (6 vs. 12 ml/kg) after major noncardiac surgery.

In patients undergoing thoracotomy and requiring one-

lung ventilation (OLV), three RCTs have evaluated

the impact of different ventilatory settings. Schilling

et al. [58] found reduced alveolar concentrations of

TNF-a and soluble intercellular adhesion molecules

(ICAMs) in patients ventilated with small vs. large VT

(5 vs. 10 ml/kg). Confirming these positive results,


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Table 2 Randomized controlled trials assessing the effects of different modes of ventilation

Reference n Type of surgery Ventilation strategy Effects of low vs. high VT

Two-lung ventilationWrigge et al. [48] 39 Visceral, orthopedic

and vascular5 ml/kg ZEEP vs. 5 ml/kg

10 cmH2O PEEP vs.15 ml/kg 10 PEEP

Similar plasma cytokine levels

Wrigge et al. [49] 32 Visceral 6 ml/kg 10 cmH2O PEEPvs. 12–15 ml/kg ZEEP

Similar time course of cytokines in trachealaspirate and plasma

Choi et al. [50] 40 Visceral 6 ml/kg cmH2O PEEPvs. 12 ml/kg ZEEP

Thrombin–antithrombin complex, activatedprotein C in BALF, thrombomodulinin BALF

Wolthuis et al. [51] 40 Visceral 6 ml/kg 10 cmH2O PEEPvs. 12 ml/kg ZEEP

Similar levels of TNF-a, IL-1, MIP-1 in BALF,IL-8 in BALF, myeloperoxidase and

elastase in BALF, similar levels of IL-6 andIL-8 in plasma

Reis-Miranda et al. [52] 62 Cardiac 4–6 ml/kg 10 cmH2OPEEPþRM vs.6–8 ml/kg 3 cmH2O PEEP

IL-8 and IL-10 in plasma

Chaney et al. [53] 25 Cardiac 6 ml/kg 10 cmH2O PEEPvs. 12 ml/kg ZEEP

PaO2/FIO2, static lung compliance

Zupancich et al. [54] 40 Postcardiac 6 ml/kg 10 cmH2O PEEPvs. 10–12 ml/kg3 cmH2O PEEP

IL-6 and IL-8 in BALF and plasma

Koner et al. [56] 44 Cardiac 6 ml/kg 5 cmH2O PEEPvs 0.10 ml/kg ZEEP vs.10 ml/kg 10 cmH2O PEEP

Similar plasma TNF-a and IL-1, similarPaO2/FIO2

Lee et al. [57] 103 General 6 vs. 12 ml/kg Pulmonary infection, duration of MVWrigge et al. [55] 44 Cardiac 6 ml/kg 10 PEEP

vs. 12 ml/kg ZEEPTNF-a in BALF, similar plasma cytokine levels

One-lung ventilationWrigge et al. [49] 32 Lung resection 6 ml/kg 10 cmH2O PEEP

vs. 12–15 ml/kg ZEEPSimilar time course of cytokines in tracheal

aspirate and plasmaSchilling et al. [58] 32 Lung resection 5 ml/kg ZEEP vs. 10 ml/kg ZEEP TNF-a and sICAM in BALF, similar levels of

albumine, elastase, IL-8 and IL-10Michelet et al. [59] 52 Esophagectomy 5 ml/kg 5 cmH2O PEEP vs.

9 ml/kg ZEEPIL-1, IL-6, IL-8 in plasma, PaO2/FiO2 andlung water content, duration of MV

BALF, bronchoalveolar lavage fluid; MV, mechanical ventilation; PaO2/FIO2, ratio of arterial oxygen pressure to fractional inspiratory oxygen pressure;PEEP, positive end-expiratory pressure; RM, recruitment maneuver; sICAM, soluble intercellular adhesion molecules; TNF, tumor necrosis factor;ZEEP, zero-end expiratory pressure.

Michelet et al. [59] reported an attenuated systemic proin-

flammatory response [lower plasma levels of interleukin

(IL)-6], reduced EVLWI and improved oxygenation index

allowing earlier extubation in patients undergoing esopha-

gectomy who received low VT (5 ml/kg) with a PEEP level

of 5 cmH2O (compared with VT of 10 ml/kg with zero

PEEP). In contrast, Wrigge et al. [49] failed to document

any difference in systemic inflammatory markers, blood

oxygenation index and respiratory mechanics between

thoracic surgical patients assigned to receive either mech-

anical ventilation with VT of 6 ml/kg and PEEP of

10 cmH2O or a VT of 12–15 ml/kg without PEEP.

Although a growing body of scientific knowledge indicates

that the ‘traditional’ ventilatory settings may be injurious

in the healthy lungs, a clear demonstration of clinical

outcome benefits induced by LPV is still lacking. There-

fore, we are awaiting the results of well designed RCTs

with sufficient power and pertinent clinical endpoints,

comparing conventional ventilation to LPV protocols.

Hyperperfusion and oxidative injuries

In-vitro studies have shown that cyclic stretch and hyper-

oxic exposure of lung epithelial and endothelial cells


trigger formation of ROIs/RNIs and induce complex

patterns of cell death. These findings have been con-

firmed in animal and human studies.

In rabbits ventilated with large VT and moderate hyperoxia

(FIO2¼ 0.5), Sinclair et al. [60] reported a loss of alveolar–

capillary barrier integrity and larger increase in local

inflammatory mediators (IL-8 and TNF-a) than animals

exposed either to room air or to hyperoxia without large VT.

Consistent with these results, Funakoshi et al. [61]

reported an upregulation of proinflammatory cytokines

and myeloperoxidase upon reventilation, though indices

of pulmonary capillary permeability remained unchanged.

Likewise, in anesthetized pigs subjected to thoracotomy

and OLV (VT of 10 ml/kg, PEEP of 5 cmH2O and FIO2 of

0.4), Kozian et al. [62] showed hyperperfusion, ventilation–

perfusion mismatch and diffuse tissue damage that pre-

dominated in the dependent nonoperated lung.

In three patients with reexpansion pulmonary oedema,

Her and Mandy [63] observed leukocyte-mediated ALI

in the contralateral lung along with decreased leuko-

cytes and platelet counts upon reoxygenation of the col-

lapsed lung. In another clinical study involving patients


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undergoing lobectomy, Cheng et al. [64] reported for-

mation of ROIs during lung reinflation after OLV (VT of

10 ml/kg and FIO2 of 1.0) although antioxidant markers

and EVLWI remained unchanged.

Taken together, these data suggest that hyperoxic/

mechanical injuries predominate in the nonoperated

lung, whereas the operated lung is prone to atelectasis

formation due to impaired surfactant and direct surgical

manipulation. An imbalance between antioxidants and

excess production of RNIs/ROIs has been incriminated

in perpetuating the inflammatory process and causing

cellular damage by oxidizing nucleic acids, proteins and

membrane lipids [65].

Genetic factors

Only a fraction of patients exposed to ALI-inciting events

progress to the full clinical syndrome. Hence, major

interest has been focused on the identification of genetic

factors characteristic of ALI susceptibility. Relevant gene

variants or single-nucleotide polymorphisms (SNPs) in

these ALI candidate genes have been tested for differ-

ences in allelic frequency in cohort studies [66]. This

approach has yielded a number of candidate genes con-

tributing towards an ALI phenotype, namely genes cod-

ing for angiotensin-converting enzyme (ACE), surfactant

protein B, heat-shock protein 70, pre-B-cell colony

enhancing factor, myosin light-chain kinase and macro-

phage migration inhibitory factor.

Using microarray technology, the transcription factor

Nrf2 (NF-E2 related factor 2) has been shown to up-

regulate the protective detoxifying enzymes in response

to oxidative stress [67]. Genetic disruption of the Nrf2

has been associated with an overexpression of proinflam-

matory cytokines and increased risk of ALI due to hyper-

oxia and high VT. In line with these results, Marzec et al.[68] identified six novel SNPs for Nrf2 in a nested case–

control study. Patients with the �617 SNP (A/or C/A

allele) were at greater risk of posttrauma ALI relative to

patients bearing the wild type (�617 C) [odds ratio (OR)

6.4; 95% confidence interval (CI) 1.3–30.8].

In patients undergoing esophagectomy (n¼ 152), pul-

monary morbidity has been associated with an ACE

insertion/deletion polymorphism; the D/D genotype

was found to be highly predictive of major pulmonary

complications (adjusted OR 3.12; 95% CI 1.01–9.65) [69].

Edema clearance mechanisms

Removal of the excess intraalveolar fluid is mainly influ-

enced by epithelial b-adrenergic receptors and lectin-like

domain of TNF-a that regulate the active sodium trans-

port through alveolar type I and II cells [70–72]. In heart

failure, high-altitude lung edema and various models of

ALI, alterations in these b-adrenergic signaling pathways


have been incriminated as initiating or aggravating factors

[71]. Likewise, the interactions with ROIs/RNIs and

nuclear factor-kB-dependent activation of the inducible

nitric oxide synthase may result in downregulation of b2-

adrenergic receptor in response to surgical trauma and

OLV/reoxygenation. Hence, early and severe interstitial/

alveolar lung edema may develop in patients with

deficient b-adrenergic-mediated fluid clearance mechan-

isms.

Novel perioperative approachesPreliminary data suggest some advantages for volatile

anesthetics during OLV. Indeed, desflurane has been

associated with lesser recruitment of neutrophils and

reduced concentrations of inflammatory biomarkers in

the BALF [elastase, soluble intercellular adhesion mol-

ecules (sICAM), TNF-a, IL-8 and IL-10] than propofol

anesthesia [73].

Regarding ventilatory settings, the emerging concept of

PLV based on the ‘open-lung approach’ aims to limit

alveolar distension with low (but physiological) VT while

attenuating the loss of functional residual volume and

preventing the formation of atelectasis with PEEP and

lung recruitment maneuvers [74,75]. Using ‘low VT’

combined with PEEP does not favor the development

of atelectasis, whereas the pressure-controlled mode of

ventilation (vs. volume-controlled mode) may lower peak

airway pressure with similar blood oxygenation indices, at

least in patients without severe lung disease [76,77].

Controversies still surround the question of the optimal

FIO2; high levels (60–80%) may reduce the risk of surgi-

cal-site infections but promote atelectasis and ROI for-

mation [78]. Conversely, low–moderate FIO2 (30–50%)

might be an appropriate compromise to ensure satisfactory

blood oxygenation and limit secondary lung injuries.

Considering the importance of the hydrostatic pulmonary

pressure, a restrictive or goal-directed fluid approach

coupled with the assessment of intrapulmonary fluid

volume is strongly recommended for the intraoperative

period and the first 24–48 h after major lung resection.

Postoperatively, high-risk thoracic patients may benefit

from noninvasive ventilation and inhaled b2-adrenergic

therapy. In a small RCT including 32 patients with a

moderate degree of chronic obstructive pulmonary dis-

ease, better postoperative recovery of pulmonary func-

tion was reported when noninvasive pressure support

ventilation was applied prophylactically before and

shortly after lung resection [79]. In 21 patients at high

risk of pulmonary edema from either a cardiogenic or

noncardiogenic cause, the impact of aerosolized broncho-

dilators has been investigated using the single-dilution


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indicator method [80]. Using a crossover design, salbu-

tamol (vs. ipratropium) was shown to accelerate the

resolution of postoperative lung edema and improve

blood oxygenation without causing adverse cardiac

events. In addition, b2-adrenergic agonists may also pre-

vent or attenuate ALI by blunting the release of proin-

flammatory cytokines, reducing chemotaxis and neutro-

phil degranulation as well as protecting the integrity of

the alveolar–capillary barrier [81].

ConclusionThis review has attempted to summarize and update key

features regarding major mortality and ALI following

thoracic surgery. Animal studies and transitional biology

have provided new insights into the fundamental mech-

anisms of ALI that might evolve towards new targeted

therapeutic tools.

Several changes in perioperative management have

already been implemented, particularly in high-risk

patients: an ‘open-lung’ approach (low VT, PEEP and

recruitment), titrated fluid regimen, assessment of pul-

monary fluid compartment and early treatment of lung

edema with noninvasive ventilation, aerosolized b2-

adrenergic agonists or both.

AcknowledgementsThe present study was supported by a grant from the LancardisFoundation in Sion (Switzerland).

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