Alveoli are most likely to collapse (resulting in atelectasis) when which condition exists?

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Education| January 2022

Congli Zeng, M.D., Ph.D.;

Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts

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David Lagier, M.D., Ph.D.;

David Lagier, M.D., Ph.D.

Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts

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Jae-Woo Lee, M.D.;

the Department of Anesthesia, University of California San Francisco, San Francisco, California

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Marcos F. Vidal Melo, M.D., Ph.D.

Marcos F. Vidal Melo, M.D., Ph.D.

Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts

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This article is featured in “This Month in Anesthesiology,” page A1.

Martin J. London, M.D., served as Handling Editor for this article.

C.Z. and D.L. contributed equally to this article.

Submitted for publication December 4, 2020. Accepted for publication July 13, 2021. Published online first on September 8, 2021.

Address correspondence to Dr. Vidal Melo: Massachusetts General Hospital, 55 Fruit Street, Boston, Massachusetts 02114. . Anesthesiology’s articles are made freely accessible to all readers on www.anesthesiology.org, for personal use only, 6 months from the cover date of the issue.

Anesthesiology January 2022, Vol. 136, 181–205.

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The term atelectasis derives from the Greek words atelez, which means “imperfect,” and ektasiz, which means “expansion.” Pulmonary atelectasis thus refers to the incomplete expansion of alveoli and terminal bronchioles. In its paradigmatic form, atelectasis is represented by complete deaeration of lung units. Atelectasis is pervasive in anesthesia practice, and already in 1963, Bendixen et al.1  demonstrated that general anesthesia with mechanical ventilation resulted in deterioration of intraoperative oxygenation and compliance in patients with normal preoperative lung function. Brismar et al.2  subsequently demonstrated that such deterioration was associated with pulmonary densities revealed by computed tomography. In addition to physiologic impairment, pulmonary atelectasis could contribute to perioperative lung injury.3  The clinical presentation of significant atelectasis in surgical patients is variable from no sequalae to prolonged oxygen requirement to hypoxemia requiring endotracheal intubation and ventilation to even acute respiratory distress syndrome [ARDS]. This article focuses on the perioperative period and aims to review the etiology of pulmonary atelectasis and provide a pathophysiologic discussion including biologic as well as biomechanical processes.

Physiologic Principles of Bronchiolar and Alveolar Expansion

Bronchioles and alveoli walls are composed of cells and extracellular matrix and covered by a liquid film on their luminal side containing surfactant. Each of these elements are exposed to expanding and collapsing forces.

Stresses Acting on Bronchioles and Alveolar Walls

Normal stress is the force per unit of area [A] perpendicular to the surface where the force is exerted. Three main components of the normal stresses acting on bronchioles and alveolar walls determine their expansion [fig. 1]4 : fluid pressure, tethering stress, and surface tension. A conceptual note on the physical meaning of these mechanical components is that, although related, they are not equivalent as pressure is a scalar [a physical quantity having only magnitude], whereas stress is a vector [a physical quantity with direction and magnitude].

Fig. 1.

Pressures and forces acting on alveolar and bronchiolar walls and visceral pleura surface. Fi, inward tethering; Fo, outward tethering; Fw, circumferential component of force applied by the layer of surface-active fluid; Palv, alveolar pressure; Pi, inside pressure; Po, outside pressure; Ppl, pleural pressure.

Fig. 1.

Pressures and forces acting on alveolar and bronchiolar walls and visceral pleura surface. Fi, inward tethering; Fo, outward tethering; Fw, circumferential component of force applied by the layer of surface-active fluid; Palv, alveolar pressure; Pi, inside pressure; Po, outside pressure; Ppl, pleural pressure.

Close modal

• [1] Fluid pressure represents the pressure applied by fluids [gas or liquid] to the surface of the alveolar or bronchiolar wall. The net result of the fluid pressures derives from the difference of inside [Pi] and outside [Po] pressures, expressed by the formulation of transmural pressure:

Transmural​press ure=inside​pressure Pi− outside​pressure [Po]

• [2] Tethering stress represents radial stresses caused by attachments of bronchioles and alveolar walls to adjacent structures through the tissue matrix. The radial tethering stress is mechanically transmitted to alveoli, bronchioles, and pleural surface through a network of collagen and elastin fibers composing the extracellular matrix in the pulmonary septa. These fibers are the force-bearing elements. The parenchymal cells themselves [epithelial and endothelial cells] have a lower mechanical contribution. Preserved lung interstitial architecture thus ensures the transmission of the tethering stress inside the lung parenchyma.5  The net effect of those stresses applied inside [Fi/A] and outside [Fo/A] the bronchioles or alveolar walls can be expressed as [fig. 1]:

Net tethering stress= ∑​FoA− ∑​FiA

• [3] Surface tension represents the inward-acting radial stress arising from the circumferential components of forces applied by the thin layer of fluid lining the bronchioloalveolar walls resulting from the effect of the surface tension [T]. For a spherical structure with radius R [alveoli], the Young–Laplace pressure equation expresses the relationship between the pressure difference across the fluid interface [Pw] and the surface tension as:

For a cylindrical structure of radius R [bronchioles], the relationship is:

Accordingly, the pressure difference across the fluid interface becomes substantial for small R. The surface tension is likely more important in the cylindric bronchioles than in alveoli, which are not strictly spherical.6  Pulmonary surfactant, a lipoprotein complex secreted by type II alveolar epithelial cells, is a critical biomechanical stabilizer to bronchioles and alveoli expansion.7  Its presence at the air–liquid interface strongly reduces surface tension, decreasing the magnitude of this collapsing contribution.

The balance of these forces and pressures allow for quantitative relationships in specific conditions [fig. 1]:

• •

  In equilibrium, the balance of the expanding and collapsing radial stresses acting on bronchioles or alveolar walls should be zero4 :

• •

  No external tissue attachments are present at the pleural surface. Consequently, Fo = 0 and transmural pressure is determined by Pi [= alveolar pressure, Palv] and Po [= pleural pressure, Ppl]. Radial stresses corresponding to the sum of inward-acting tissue and surface forces are balanced by the transmural pressure [Palv – Ppl] acting on the pleural surface area [Apl]. Because the radius of the pleural surface curvature is large, the effect of surface tension is negligible [Pw ≈ 0]. Accordingly, the balance of forces at the pleural surface is:

• •

  Within the lung, if all airways are patent, pressures on the two sides of alveolar walls [i.e., Pi and Po] equal the same alveolar pressure [Palv]. Therefore, transmural pressure between adjacent alveoli is null, and the outward-acting tethering force [Fo] counteracts inward-acting tissue and surface forces:

The Elastic Recoil of the Lung

Lung elastic recoil represents the propensity of lung tissue to shrink and is the main physiologic mechanism of passive exhalation. It results from the combined effects of: [1] extracellular matrix elastic fibers [contributing to Fi] and [2] bronchioloalveolar surface tension.4,7  Accordingly, degradation of the elastic fibers in the extracellular matrix, as during emphysema, reduces elastic recoil, thus reducing the expiratory capacity and acting against alveolar collapse.8  Conversely, diseases leading to quantitative or qualitative surfactant impairment increase surface tension and facilitate alveolar collapse.7 

The Interdependent Lung Expansion

Pulmonary interdependence represents the interplay of mechanical forces among lung tissue components: alveolar units, airways, vasculature, and extracellular matrix. For instance, interdependence during lung expansion transmits tethering stress to traction airway walls outwards.5,9–11  Interdependence relies on normal lung architecture, including the extracellular matrix fibers.12  In a homogeneous lung, outward tethering stresses [ΣFo/Apl] are transmitted from the visceral pleura surface to the innermost lung regions. These stresses are determined by the elastic recoil pressure of the lung Pel[L],13  equal to the transmural pressure at the pleural surface:

A positive Pel[L], transmitted to the inner lung through interdependence, is the primary determinant of lung expansion. During awake spontaneous breathing, Ppl is negative throughout the pleural space, leading to a positive Pel[L] as Palv = 0 [= atmospheric pressure]. In contrast, Pel[L] ≤ 0 is associated with unphysiologic conditions resulting in lung collapse, such as open-chest or general anesthesia with mechanical ventilation.

The transpulmonary pressure [PL] has been advanced as a surrogate of the elastic recoil pressure of the lung when the alveolar pressure [Palv] can be approximated by the pressure at the airway opening [Pao]. This occurs when respiratory flows are zero [usually at end expiration and end inspiration] and no gas trapping exists13 :

Hence, a positive transpulmonary pressure throughout the respiratory cycle is required to maintain alveolar expansion.

Mechanisms of Atelectasis in the Perioperative Period

General anesthesia, mechanical ventilation, and surgical interventions produce several biophysical factors promoting lung tissue collapse [fig. 2]. Three major interrelated collapsing factors influence the balance of forces discussed above and contribute to perioperative atelectasis: increased pleural pressure, low alveolar pressure, and surfactant impairment. As a result of these factors, continuous or intermittent airway and alveolar closure occur, presumably more commonly the first than the latter.14,15 

Fig. 2.

Mechanisms producing atelectasis in the perioperative period. [A] Normal lung unit in awake conditions. Adequate inspiratory [Pi] and expiratory [Pe] intraluminal pressure and bronchiolar or alveolar tethering stress associated with negative pleural pressure [Ppl] allow for the normal opening of the bronchiole and a normal alveolar ventilation [⁠V.A]. Alveolar gas absorption is physiologic due to physiologic V.A/ lung perfusionand atmospheric fraction of inspired oxygen [FiO2]. Normal surfactant reduces alveolar surface tension. [B] Lung unit exposed to perioperative atelectasis. The increase in pleural pressure [Ppl] due to extrinsic or intrinsic compression [circle 1] is responsible for the loss of expansion and reduced alveolar ventilation [⁠V. A]. Increased alveolar gas absorption [circle 2] reduces intraluminal alveolar pressure [Palv]. Low V.A/Q.⁠, high FiO2, and low mixed venous oxygen partial pressure [Pv¯O2] may participate in such gas exchange imbalance. Quantitative or qualitative surfactant impairment leads to higher surface tension and facilitates alveolar collapse [circle 3]. FiN2, fraction of inspired nitrogen; Pc′O2, end-capillary oxygen partial pressure.

Fig. 2.

Mechanisms producing atelectasis in the perioperative period. [A] Normal lung unit in awake conditions. Adequate inspiratory [Pi] and expiratory [Pe] intraluminal pressure and bronchiolar or alveolar tethering stress associated with negative pleural pressure [Ppl] allow for the normal opening of the bronchiole and a normal alveolar ventilation [⁠V.A]. Alveolar gas absorption is physiologic due to physiologic V.A/ lung perfusionand atmospheric fraction of inspired oxygen [FiO2]. Normal surfactant reduces alveolar surface tension. [B] Lung unit exposed to perioperative atelectasis. The increase in pleural pressure [Ppl] due to extrinsic or intrinsic compression [circle 1] is responsible for the loss of expansion and reduced alveolar ventilation [⁠V. A]. Increased alveolar gas absorption [circle 2] reduces intraluminal alveolar pressure [Palv]. Low V.A/Q.⁠, high FiO2, and low mixed venous oxygen partial pressure [Pv¯O2] may participate in such gas exchange imbalance. Quantitative or qualitative surfactant impairment leads to higher surface tension and facilitates alveolar collapse [circle 3]. FiN2, fraction of inspired nitrogen; Pc′O2, end-capillary oxygen partial pressure.

Close modal

Increased Pleural Pressure

Pleural pressure is the pressure within the pleural cavity. It varies regionally across the pleural space depending on anatomical and physiologic interactions between the lung parenchyma, chest wall, and gravity.16  General anesthesia affects such interactions increasing regional pleural pressure [e.g., dorso-caudal in supine patients], resulting in negative transpulmonary pressure and compressive atelectasis [fig. 2].

Functional Changes of the Diaphragm and Additional Chest Wall Components.

The chest wall can be understood as composed by two functional portions: an elastic portion represented by the rib cage and abdominal wall and a constant weight component exerting a hydrostatic pressure represented by the abdomen. Changes in these portions will affect pleural pressure and lung expansion in the perioperative period, in line with the previously discussed equilibration of forces throughout the lung. The diaphragm is the primary muscle of lung ventilation and, consequently, significantly contributes to lung expansion and atelectasis development during anesthesia. For example, in anesthetized intubated patients without cardiopulmonary disease, phrenic nerve stimulation to produce diaphragm contraction reduces atelectatic area by approximately 33% as compared to mechanical ventilation with equal tidal volumes.17 

In supine spontaneously breathing humans, diaphragmatic displacement and lung expansion are larger in dependent than nondependent lung regions.18,19  This is due to the diaphragm dome shape with a smaller dependent radius of curvature, higher dependent stretch producing more favorable dorsal length-tension relationships, and possibly larger number of muscle fibers20  and higher compliance of the crural than costal diaphragm.18  Diaphragm tension reduces the transmission of abdominal pressure to the lungs.21  Reduction or loss of such diaphragmatic tone during anesthesia thus affects the net balance of stresses acting on the lungs, not only reducing the preferential dependent displacement of the diaphragm but also facilitating the transmission of abdominal pressure to the lungs. This results in a cephalad shift of the dependent diaphragm with dependent lung compression and atelectasis22,23  and no change or caudad shift of nondependent regions.19,23  Relaxation of accessory respiratory muscles such as intercostals, scalenes, and sternocleidomastoids further contribute to reduction in cross-section chest area and lung aeration [fig. 3]. In spontaneously breathing normal subjects receiving volatile anesthesia, the activity of parasternal muscles is abolished, and phasic expiratory activity in abdominal and lateral rib cage muscles is enhanced,24  contributing to caudad-dependent atelectasis.23  Muscle paralysis compounds to the dependent cephalad shift of the diaphragm and atelectasis during general anesthesia,23  as the balance between alveolar pressure and the gravity-dependent hydrostatic pressure of abdominal contents becomes the main determinant of diaphragm motion.19  Ultimately, atelectasis that is preferentially dependent and caudad is detected in 90% of a broad population of patients without cardiopulmonary disease undergoing general anesthesia,25  with up to 20 to 25% of initially normal lung either atelectatic or poorly aerated in transverse computed tomography during anesthesia.26 

Fig. 3.

Changes in chest wall shape due to general anesthesia in a supine patient. During awake spontaneous breathing, contraction of diaphragm and accessory muscles of respiration maintain lung expansion. Loss of muscular tone during anesthesia is associated with cephalad motion of the dependent diaphragm, reduction in cross-sectional chest area, and generation of nongravitational compressive forces [i.e., cephalocaudal gradients]. Together with gravitational forces and potential increase in intrathoracic blood volume, these factors contribute to reduction of lung volume and lung collapse, particularly on the dorsal and basal lung regions.

Fig. 3.

Changes in chest wall shape due to general anesthesia in a supine patient. During awake spontaneous breathing, contraction of diaphragm and accessory muscles of respiration maintain lung expansion. Loss of muscular tone during anesthesia is associated with cephalad motion of the dependent diaphragm, reduction in cross-sectional chest area, and generation of nongravitational compressive forces [i.e., cephalocaudal gradients]. Together with gravitational forces and potential increase in intrathoracic blood volume, these factors contribute to reduction of lung volume and lung collapse, particularly on the dorsal and basal lung regions.

Close modal

Increased abdominal pressure as present with pneumoperitoneum, obesity, abdominal compartment syndrome, peritonitis, or abdominal shift of intrathoracic blood27,28  produces further imbalance of net stresses on the lung, because it exposes the dorso-caudal lung to higher pleural pressure and susceptibility to atelectasis,2,29  with cephalad shift of both diaphragm and intra-abdominal organs.19,23,27  Of note, cephalad-outward movement of the lower ribs potentially produced by those factors can increase the cross-section of the lower chest and partially compensate for the loss of lung volume.21 

Although gravity has been frequently cited as a key determinant of lung expansion, cephalocaudal gradients of lung expansion present in large animals30  and humans22,31  indicate the relevance of factors other than gravity. These factors include the matching of the lung to the thoracic cavity and the partially independent displacement of lobes, which are relevant determinants of regional lung expansion in supine and prone positions beyond gravitational factors.30,32  Perioperative chest wall reshaping is influenced by body position, with proning allowing for recruitment of dorso-caudal lung.33 

Postoperative respiratory muscle dysfunction, particularly diaphragm dysfunction, has been documented after abdominal,34  thoracic,35  and cardiac surgery.36  It facilitates the development of atelectasis as demonstrated by the significantly larger fraction of patients with atelectasis 24 h after thoracic surgery in the presence of postoperative ultrasound-diagnosed diaphragmatic dysfunction [35%] than in its absence [13%].35  Diaphragm dysfunction can persist from a day to a week37,38  and even up to a year.39  It can occur because of direct injury to the diaphragm36  or phrenic nerve40  or because of indirect factors such as phrenic nerve dysfunction37,41  and impaired thoracoabdominal mechanics.42  These factors could compound with previous diaphragmatic compromise, for example, as present in neuromuscular disorders, sepsis,43  abdominal hernias,44  and potentially obesity.45  Of note, diaphragmatic function could conversely affect regional lung inflammation by producing local high transpulmonary pressures as shown by the observation that spontaneously breathing lung-injured pigs exposed to low positive end-expiratory pressure [PEEP] present more dependent lung inflammation than those receiving high PEEP.46 

Although anesthetics [e.g., isoflurane, sevoflurane, and propofol] can compromise diaphragmatic function,47–49  they do not affect contractility.50  The diaphragmatic electromyographic activity can also be impaired by unwarranted administration of cholinesterase inhibitors, for example, neostigmine followed by sugammadex in humans51  or neostigmine administered after full recovery from neuromuscular block in rats.52 

Intrapulmonary Gravity Gradient.

The weight of the nondependent lung compresses the dependent lung and pleural space determining pleural pressure increases along the vertical axis11  with transpulmonary pressure reduction in dependent lung regions.53,54  Pulmonary edema increases the weight of the lung tissues, increasing the risk of dependent atelectasis caused by the superimposed hydrostatic pressure.54,55  Body position influences the effect of intrapulmonary compression by modulating the volume of dependent lung. For instance, the triangular shape of the lungs with the large dorsal base results in a greater volume of dependent lung in the supine than in the prone position.55,56 

Compression by Intrathoracic Elements.

In supine patients, the mediastinal weight, particularly the heart, has been associated with pleural space compression and preferential retrocardiac lung collapse.57  Pleural effusions may also compress the lung. However, the effusion volume does not entirely translate into compression58  because of the compliance of the chest wall. For instance, in ARDS patients, chest wall expansion in the presence of a pleural effusion accommodates ~70% of the effusion volume.58,59 

Low Alveolar Pressure

The concept of critical opening pressure has been introduced as the minimal alveolar pressure [Palv in the previously described formulation] required to counteract the regional effect of collapsing forces.60  Accordingly, lung units are expanded when alveolar pressure is higher than the critical opening pressure. A parallel concept is that of critical closing pressure, i.e., the alveolar pressure below which open lung units collapse. Mean closing pressure has been estimated as 6 cm H2O in a small number of anesthetized mechanically ventilated patients,61  an interesting value to compare to the usual initial clinical setting of 5 cm H2O. As determined experimentally in animal and computational models,62,63  the critical closing pressure is lower than the critical opening pressure due to lung hysteresis, i.e., the difference between the inspiratory and expiratory components of the pulmonary pressure–volume curve, produced by opening of previously nonaerated peripheral airspaces.64  Due to the vertical dependence of pleural pressures, critical opening pressures are higher in dependent regions as lung regions exposed to positive pleural pressure require alveolar pressures higher than these pleural pressures to achieve positive transpulmonary pressure and expansion.

The rationale for the use of PEEP derives from such a concept, ultimately aiming to keep alveolar pressures above critical closing pressures at end-exhalation to prevent lung collapse. Local variation in critical opening and closing pressures conditions the regions expanded and kept inflated throughout the breathing cycle at a given PEEP. Even normal lungs, when mechanically ventilated without PEEP for many hours, will progressively lose aeration preferentially in dorsal regions.65  Of note, lung hysteresis imply that the PEEP required to keep lung regions open is lower than that required to open them [fig. 4].66  This provides support to the practice of recruiting the lungs at pressures higher than those used during steady state mechanical ventilation.

Fig. 4.

Pulmonary pressure–volume curve during inhalation and exhalation showing lung hysteresis. The shape of the lung pressure–volume curve is sigmoidal. There are three main portions of the curve. The initial portion [blue] of lung recruitment at low pressures and volumes is related to low compliance [i.e., the change in volume [ΔV] divided by the change in pressure [ΔP] is low]. This is followed by a portion with a linear relationship between volume and pressure with higher compliance [ochre]. Finally, hyperinflation ensues at high pressures and volumes with return of lower compliance [red]. The transition between the first and second portions indicate that critical opening pressures for a large number of bronchoalveolar regions has been reached [lower inflection point]. Note the higher pressure during inhalation to reach the same lung volume as during exhalation. Modified from Radford.66 

Fig. 4.

Pulmonary pressure–volume curve during inhalation and exhalation showing lung hysteresis. The shape of the lung pressure–volume curve is sigmoidal. There are three main portions of the curve. The initial portion [blue] of lung recruitment at low pressures and volumes is related to low compliance [i.e., the change in volume [ΔV] divided by the change in pressure [ΔP] is low]. This is followed by a portion with a linear relationship between volume and pressure with higher compliance [ochre]. Finally, hyperinflation ensues at high pressures and volumes with return of lower compliance [red]. The transition between the first and second portions indicate that critical opening pressures for a large number of bronchoalveolar regions has been reached [lower inflection point]. Note the higher pressure during inhalation to reach the same lung volume as during exhalation. Modified from Radford.66 

Close modal

Resistance of Upstream Airways.

The transmission of upper airway pressures to distal lung regions, i.e., the proximity between Palv and Pao, depends on the patency of regional airways [fig. 2]. Increased airway resistance, secondary to airway constriction, obstruction, or compression13  determines a pressure drop in the distal lung with local alveolar pressures potentially lower than tracheal pressures [Palv