Core principles of respiratory physiology and pathophysiology in critical illness

What are respiratory mechanics and how are they measured?

Because the lung is a flexible but passive structure, gas flows to and from the alveoli driven by differences between airway and alveolar pressures—no matter how they are generated. The total pressure gradient expanding the respiratory system is accounted for in two primary ways: (1) driving gas between the airway opening and the alveolus and (2) expanding tissue against the recoil forces of the lung and chest wall. The pressure required for inspiratory flow dissipates against friction, whereas the elastic pressure that expands the respiratory system is stored temporarily in its tissues until dissipated in driving expiratory flow.

The mechanical properties of the respiratory system are those characteristics that influence the energy cost of breathing. Because pressure provides the forces driving gas flow and counterbalancing elastic recoil, assessing respiratory mechanics involves the measurement of flows, volumes (flow integrated over time), and pressures. In simplified form, the expression of these relationships, the equation of motion of the respiratory system, can be written: P = RV′ + V/C + Pex. In this equation P is the pressure applied across the entire respiratory system, R is inspiratory resistance to flow, C is inspiratory compliance, V′ and V are flow rate and the volume inspired in excess of the end-expiratory value, and Pex is end-expiratory alveolar pressure—applied positive end-expiratory pressure (PEEP) and any supplemental end-expiratory pressure generated as a result of the ventilatory pattern itself (auto-PEEP, discussed later). Although regional mechanics are of unquestioned importance in determining ventilation, gas exchange, and tissue strain, the technology available at most bedsides currently limits measurements and monitoring to the global properties of the integrated respiratory system, composed of the lungs encased by the surrounding chest wall. Pressure changes relevant only to the lungs must be assessed as the difference between the airway pressure (Paw) and the pleural pressure (Ppl) that surrounds them (defined as the transpulmonary pressure, Ptp). The esophagus provides a convenient site from which to measure the changes of intrapleural pressure that occur during tidal ventilation with a balloon-tipped catheter. It may also measure with reasonable accuracy the absolute pleural pressure across the same horizontal gravitational plane. With the airway occluded and flow stopped, pressure measured at the airway opening estimates gas pressure at the alveolar level.

Transpulmonary pressure

For any expandable compartment, such as the chest, the absolute volume and volume change depend on its flexibility (compliance) and the pressure difference inside and outside the structure ( Fig. 53.1 ). For the lung, this transmural pressure is Ptp = Paw − Ppl. Under passive conditions the corresponding transmural pressure for the integrated respiratory system is the airway pressure minus atmospheric pressure, or Paw. For the passive chest wall alone, transmural pressure is simply the average pleural pressure. Pleural pressure is not helpful in assessing chest wall compliance during spontaneous breathing, however, as its embedded musculature generates the negative pleural pressure deflections that drive tidal movement. During muscular effort, the transmural pressure acting across the lung remains the airway pressure minus intrapleural pressure difference; therefore the actual transstructural pressure to which the lung is exposed is less than the measured Paw under passive conditions and greater than the measured Paw during spontaneous or patient-assisted breathing ( Fig. 53.2 ). Because the lungs are inherently passive, their mechanical properties can be assessed during any form of spontaneous, patient-triggered but machine-assisted, or controlled, ventilation. The mechanical properties of the chest wall, in contrast, can only be directly evaluated during controlled ventilation when the actual pleural pressure acting to distend that structure can be estimated by a balloon-tipped esophageal catheter.

Key differences between active and passive breathing

It is sometimes taught that regarding the lung itself, there are few perceptible differences in mechanical behaviors between passive and active inflation. Although that statement holds approximately true for global transmural pressures and volume measurements made in healthy excised lungs, it is not precisely accurate in vivo—especially not for acutely injured lungs. Active contraction of the diaphragm decreases the local transmural pressures of nearby alveoli somewhat more than average, whereas the nondependent zones within a passive chest may be surrounded by lower pleural pressures and therefore experience greater resting transpulmonary pressures and lesser swings of transpulmonary pressure during tidal inflation. Such regional differences are accentuated by conditions that increase lung weight and produce heterogeneous mechanics, such as acute respiratory distress syndrome (ARDS) ( Fig. 53.3 ). Not only does regional expansion and distribution of volumes differ in accordance with modifications of effective local compliance by spontaneous breathing efforts, but the filling and distention of the pulmonary blood vessels are significantly different as well ( Fig. 53.4 ). Negative pleural pressure swings and lower mean pleural pressures promote venous return and pulmonary vascular filling, whereas positive pleural swings and higher mean pressures impede venous return and pulmonary vascular filling. Greater vascular filling tends to reduce the compliance of the lung parenchyma.

Pulmonary elastance and compliance

In the clinical setting, the global mechanical properties of the chest are assessed during passive mechanical ventilation by the pressures and volume changes measured at the airway opening. One routinely used value that characterizes the capacity and stiffness of the respiratory system is termed compliance, the ratio of a volume change to the static pressure difference that caused it. Compliance, C, is the inverse of elastance, E, defined as the ratio of pressure change required to produce a volume change. Because the lungs are enclosed by the chest wall, they share equivalent volumes. Consequently, under passive conditions the total positive alveolar pressure partitions itself into two components that expand the lungs and chest wall. The corresponding elastance components add in series: Ers = El + Ew ( Fig. 53.5 ). In contrast, compliances of the lungs and chest wall add in parallel: 1/Crs = 1/Cl +1/Cw. Therefore even though Crs is often used clinically to assess the elastic properties and capacity of the lung, the relationship of Crs to Cl is not entirely straightforward: Crs = (Cl × Cw) / (Cl + Cw). It should be noted here that the surface tension of the alveolar lining liquid film, increased by inflammation and attenuated by functional surfactant, may dramatically affect the lung’s flexibility.

The Crs and Cl can be reduced by depleting the number of open lung units available to ventilate and by altering their individual mechanical properties. This dual interpretation of compliance assessed at the airway opening is reflected in the sigmoidal shape of the inflation pressure-volume curve, which becomes more pronounced in the setting of acute parenchymal disorders, such as acute respiratory distress syndrome (ARDS) ( Fig. 53.6 ). Under such conditions, increases of airway pressure made from low values near relaxation tend to impressively recruit previously collapsed alveoli, improving the Crs measured at the airway opening. As pressure builds to higher levels, however, this recruiting tendency progressively diminishes. At the same time, greater transpulmonary pressures applied to units already open may stretch them into a less compliant range. This trade-off between recruitment in some zones (which often occurs disproportionately in the gravitationally dependent regions with higher surrounding pleural pressures) and stretching of open units eventually favors the latter at high volumes, bending the pressure-volume curve of the respiratory system toward the airway pressure axis.

Massive obesity is a prevalent condition in well-developed, adequately resourced countries. The increased body weight of such patients gives rise to a less compliant chest wall. Apart from the load imposed by the mass of soft tissue that overlies the chest, one important reason for this apparent noncompliance is raised intraabdominal pressure. Because the flexible diaphragm forms the caudal boundary of the chest cavity, approximately half of each increment of abdominal pressure that exceeds ∼6 cm H ₂ O is reflected the pleural space ( Fig. 53.7 ). It deserves emphasis that the overall effect of massive obesity resembles that of a static load or weight, rather than a true increase of elastance that raises pressure in direct proportion to increments of lung volume.

Energetics of inflation

When a pressure difference is applied to the passive respiratory system, that total pressure (Paw) must be accounted for by its dynamic component that overcomes flow resistance (Pr) and its “elastic” components that expand the chest. At end inflation, the latter is composed of the elastic pressure that corresponds to the tidal volume, known as the driving pressure (DP = Vt/C), and the pressure above the ambient baseline, known as positive end-expiratory pressure (PEEP). Expressed as an equation, end-inspiratory pressure is:

The mechanical energy (or work, W) delivered to cause a volume change of the passive respiratory system is the product of total airway pressure and volume—on a two-dimensional surface, a pressure × volume area. This equivalence between energy and P × V area is made more intuitive by recalling that energy is a force-length product, where length is the distance moved by an unbalanced force. Pressure is force per unit area, and volume is the product of area and length. Consequently, the P × V product has the dimensions of force × length. Assuming constant inspiratory flow, the individual expenditures of energy against the components that make up total inflation pressure are therefore approximated:

A transmural pressure × volume plot inscribes a tracing whose area quantifies the work and energy of tidal inflation ( Fig. 53.8 ). For the entire passive respiratory system, this is Paw vs. V, and under conditions of constant inspiratory flow, time is a linear analog of inflation volume. Inflation work can be further partitioned into the P × V areas that correspond to the energy required to overcome flow resistance, to deliver volume increments, and to offset PEEP ( Fig. 53.9 ). Because the same total mechanical energy is required under passive and patient-assisted conditions for flow controlled, volume-cycled breaths, the area deficit between passive and active conditions reflects the energy contribution from the patient ( Fig. 53.10 ). Similar principles of energy expenditure apply selectively to the lung when transpulmonary pressure (Paw − Ppl, rather than Paw) is substituted.

Mechanical power

Power, a measure of the rate of energy expenditure, is defined as the amount of energy per unit of time of any duration. Instantaneous power (Pi) may vary within the span of an individual inflation half-cycle by altering the flow profile ( Fig. 53.11 ). Thus the intracycle power (ICP) being applied to the passive respiratory system at volume V above the unpressurized resting value is expressed as the product of airway pressure and flow: Pi = Paw × V′, or Pi = V′(V′R) + V′ ([V/VT] × DP) + V′ (PEEP). On a longer time scale, mechanical power, as the term is currently understood in the clinical setting, is the product of the total inflation energy per cycle (Paw × V) area and the cycling frequency. Defined in this way, power is a cumulative measure of repetitive energy pulse applications per minute. Experiments indicate that if the tidal strains of each inflation cycle exceed a certain threshold, the amplitude and duration of such power exposures may be a fundamental determinant of the extent of damage that results from that ventilation pattern (ventilation-induced lung injury [VILI]).

Influence of body position on lung volume

Modification of body position is too often neglected as a therapeutic tool. Gravitational forces exert an important influence on lung volume, on ventilation distribution, and on respiratory system compliance. Under most circumstances, more upright positioning substantially increases functional residual capacity (FRC). In normal subjects, reclining decreases FRC, primarily because of the upward pressure of the abdominal contents on the diaphragm and dorsal lung compression by the heart. Normally, the FRC declines by approximately 30% (or approximately 600–900 mL for healthy persons) in shifting from the sitting to the horizontal supine position and by less in shifting from the sitting to lateral decubitus position ( Fig. 53.12 ). The magnitude of these reductions is somewhat less in older than in younger patients. Raising end-expiratory pressure with PEEP or continuous positive airway pressure (CPAP) elevates FRC. A simple calculation based on these positional losses of volume and assuming normal supine respiratory system compliance (∼80 mL/cm H ₂ O) suggests that 5–8 cm H ₂ O of PEEP may be necessary in healthy persons simply to offset the sitting-to-supine reduction of FRC. Patients of similar age with severe airflow obstruction generally lose much less volume than do normal healthy subjects when assuming supine recumbency. In massive obesity, the expiratory reserve volume (the FRC minus residual, “empty gas tank” volume) may nearly disappear even when fully upright. Sitting-to-supine changes of end-expiratory lung volume may be minimal not only for this reason but also because of positional airway closure and gas trapping.

Recumbency redistributes lung volume because it alters the geometry of the thorax. When supine, the heart directly compresses the left lower lobe bronchi, and its weight is partially supported bilaterally by the lung tissues beneath. This anatomy helps account for the tendency for atelectasis to develop commonly in the left lower lobe in postoperative and bedridden patients—especially in those with cardiomegaly. The pleural pressures in gravitationally dependent zones are less negative than at the apex. The vertical gradient of transpulmonary pressure (alveolar minus pleural pressure) is approximately 0.25 cm H ₂ O per centimeter of vertical height for normal subjects in the erect position and approximately 0.17 cm H ₂ O per centimeter for normal subjects in recumbency; consequently, local alveolar volumes are greatest in the nondependent regions. For semi-recumbent patients with edematous lungs, an intensified gravitational gradient of pleural pressure accentuates the tendency for dorsal and peri-diaphragmatic atelectasis and consolidation.

The gradient of pleural pressure is less in the prone than in the supine position, in part because of reshaping of the thoracic cavity and shifting of the weight of the heart and mediastinal contents. The supporting surface compresses the anterior chest and abdomen when prone, causing chest wall compliance to decline. Although conversion from the supine to the prone position is usually accompanied by marginal net changes of resting lung volume (<15%), there is usually a major shift of aerated lung volume toward dorsal regions ( Fig. 53.13 ).

The lateral decubitus position causes the upper lung to assume a resting volume nearly as large as it has in the sitting position, whereas the lower lung is compressed to a size similar to or less than in the supine position. Total resting lung volume is somewhat greater in the lateral decubitus than in the supine horizontal orientation.

Mechanics in disease states

Management details regarding specific diseases are provided elsewhere in this volume. Yet certain basic features of mechanics for two common classes of breathing disorders are of such fundamental importance as to deserve emphasis here.

Acute airflow obstruction

Alveolar pressure at the end of passive tidal expiration may exceed set PEEP when the expiratory phase cannot be completed to the fully relaxed position of the respiratory system before the next inspiration begins ( Fig. 53.14 ). The resulting pressure gradient driving end-expiratory flow (auto-PEEP, from the Greek word autos for “self”) persists until interrupted by inspiratory forces generated by the patient or ventilator. Total end-expiratory alveolar pressure (total PEEP) is the sum of the applied PEEP and auto-PEEP (AP). Unlike applied PEEP, AP local values (and therefore total PEEP) among lung units with diverse mechanical properties may not be the same throughout the diseased lung, and regional gas trapping may occur at higher pressures than measured at the airway opening ( Fig. 53.15 A). For this reason, the end-inspiratory static (plateau) airway pressure is generally a better indicator of hyperinflation than is the end-expiratory measurement of AP itself. Under passive conditions the detectable presence of AP and end-expiratory flow is invariably linked to increased end-expiratory distention, usually termed dynamic hyperinflation (DH). However, regional compliance determines the degree of lung unit expansion that corresponds to AP.

Determinants of dynamic hyperinflation and auto-peep

Under passive conditions, the addressable variables that tend to increase DH and auto-PEEP are increased airway resistance, long inspiratory duty cycles (Ti/Ttot), and high minute ventilation (VE). Among these targets for therapy, perhaps the most effective strategy is to reduce ventilation requirement. Lessening VE and accepting associated hypercapnia was adopted as a lifesaving approach for the treatment of intubated asthmatics well before permissive hypercapnia was implemented for ARDS. Manipulation of the ventilatory pattern (frequency and VT combination) also influences DH, but reducing Ti/Ttot is generally of limited effectiveness when VE remains unchanged. Many who require ventilatory assistance for airflow obstruction have biphasic flow curves during tidal exhalation, with the second flow-limited phase much slower than the first. ^, Such biphasic deflation patterns are more often observed in chronic obstructive pulmonary disease (COPD) than in acute asthma, but do occur in both conditions.

Dynamic hyperinflation

End-expiratory flow reliably implicates auto-PEEP during passive ventilation; however, the magnitude of flow bears little relation to the level of auto-PEEP that drives it through an undetermined upstream resistance. ^, At present, measuring static airway pressure after airway occlusion timed at end exhalation remains the method most commonly used to quantify total PEEP and to index global DH during passive ventilation. Under passive conditions, total PEEP can be measured by delaying the next breath as precisely timed airway occlusion terminates flow at the very end of the usual expiratory period. The contour of the resulting occlusion pressure helps reflect the uniformity or nonuniformity of auto-PEEP distribution (see Fig. 53.15 B). Unfortunately, this maneuver cannot be performed reliably when the patient controls the breathing rhythm because of variations in the expiratory cycle length and/or muscular effort. This occlusion estimate is neither the highest nor lowest regional end-expiratory alveolar pressure during tidal breathing, but rather the measurable volume-averaged value (see Fig. 53.15 C).

Consequences of dynamic hyperinflation and auto-PEEP

Auto-PEEP associated with DH may affect hemodynamics, predispose to barotrauma, increase work of breathing, cause dyspnea, disrupt patient-ventilator synchrony, confuse monitoring of hemodynamics and respiratory system mechanics, and interfere with the effectiveness of pressure-regulated ventilation. Barotrauma risk and the hemodynamic and energetic costs of auto-PEEP largely relate to any accompanying expansion of lung and chest wall volumes (DH)—not to alveolar pressure per se. Therefore as with the end-inspiratory plateau pressure, AP that occurs in association with stiff lungs or chest wall is less likely to be consequential than the same value measured in a setting of better respiratory system compliance.