Personalizing mechanical ventilation according to physiologic parameters to stabilize alveoli and minimize ventilator induced lung injury (VILI)

Abstract

It has been shown that mechanical ventilation in patients with, or at high-risk for, the development of acute respiratory distress syndrome (ARDS) can be a double-edged sword. If the mechanical breath is improperly set, it can amplify the lung injury associated with ARDS, causing a secondary ventilator-induced lung injury (VILI). Conversely, the mechanical breath can be adjusted to minimize VILI, which can reduce ARDS mortality. The current standard of care ventilation strategy to minimize VILI attempts to reduce alveolar over-distension and recruitment-derecruitment (R/D) by lowering tidal volume (Vt) to 6 cc/kg combined with adjusting positive-end expiratory pressure (PEEP) based on a sliding scale directed by changes in oxygenation. Thus, Vt is often but not always set as a "one-size-fits-all" approach and although PEEP is often set arbitrarily at 5 cmH₂O, it may be personalized according to changes in a physiologic parameter, most often to oxygenation. However, there is evidence that oxygenation as a method to optimize PEEP is not congruent with the PEEP levels necessary to maintain an open and stable lung. Thus, optimal PEEP might not be personalized to the lung pathology of an individual patient using oxygenation as the physiologic feedback system. Multiple methods of personalizing PEEP have been tested and include dead space, lung compliance, lung stress and strain, ventilation patterns using computed tomography (CT) or electrical impedance tomography (EIT), inflection points on the pressure/volume curve (P/V), and the slope of the expiratory flow curve using airway pressure release ventilation (APRV). Although many studies have shown that personalizing PEEP is possible, there is no consensus as to the optimal technique. This review will assess various methods used to personalize PEEP, directed by physiologic parameters, necessary to adaptively adjust ventilator settings with progressive changes in lung pathophysiology.

Keywords: ARDS; Open lung ventilation; PEEP; Personalizing mechanical ventilation; VILI.

Fig. 1

A schematic of a closed-loop feedback system that would adaptively modify ventilator settings necessary to maintain lung stability. The input is the key physiologic parameter that will be maintained by the feedback system; in this case lung stability. The set point is the parameter on the ventilator that will be adjusted to maintain the input as required. The controller is what will be adjusted to maintain the set point; in this case ventilator setting such as tidal volume and PEEP. The output is the desired physiologic effect; in this case actual lung stability. The key component of a functional feedback system is the presence of a sensor that can identify if the output is less than desirable and readjust the set point to bring the output back into compliance. Physiologic changes in lung function, such as oxygenation, dead space, lung compliance, infection points on the pressure/volume curve, stress index, imaging, or slope of the expiratory flow curve, can be used as the sensor to maintain the desired input

Fig. 2

The three mechanical mechanisms of ventilator-induced lung injury (VILI) include: a over-distension of tissue caused by excessive volume and pressure, b alveolar collapse and reopening with each breath secondary to surfactant deactivation, which causes a dynamic strain-induced tissue trauma, and c stress-concentrators caused by heterogeneous ventilation with open alveoli adjacent to collapsed or edema-filled alveoli. a An alveolar duct (yellow) is shown surrounded by alveoli represented by hexagons. Low volume/pressure (small arrows) do not over-distend alveolar ducts or distort surrounding alveoli. High volume/pressure (large arrows) over-distend alveolar ducts and distort surrounding alveoli that can lead to stress-failure in these tissues [40]. b Surfactant deactivation is a hallmark of ARDS and will result in alveolar collapse at end expiration and reopening during inspiration. Following loss of surfactant function at inspiration alveoli (hexagons) are fully inflated. However, unless end expiratory pressure is increased alveoli collapse at expiration (hexagons significantly reduced in size). This alveolar recruitment/derecruitment with each breath causes severe shear stress-induced tissue trauma [116, 117]. c Homogeneous ventilation is represented by uniformly open alveoli (hexagons) and the interdependence of these alveoli with shared wall results in a very stable structure [118]. Internal force lines (black arrows) are uniform across the homogeneously inflated lung tissue. [119]. Heterogeneous Ventilation, where isolated areas of alveolar collapse occur (blue arrows) disrupts the stability of alveolar interdependence such that stress is no longer evenly distributed across the tissue. Thus, heterogeneous tissue inflation causes a significant concentration of stress in the areas surrounding the collapse. Internal force lines bow in toward the collapsed alveoli and concentrate the stress, represented by the black stress lines becoming closer together, around the area of collapse. This stress-concentration would exacerbate tissue damage in the area surrounding the collapse [33]

Fig. 3

Methods used to set PEEP using a combined recruitment maneuver, and PEEP titration to a PO₂ + PCO₂ ≥ 400. This protocol was conducted as computed tomography (CT) was being performed to measure lung volume changes. PEEP was increased to 25 cmH₂O with a driving pressure (∆P) of 15 cmH₂O above PEEP. If a PO₂ + PCO₂ ≥ 400 was not obtained, PEEP was increased by 5 cmH₂O for 2 min, returned to PEEP 25 cmH₂O for 2 min and repeated until PO₂ + PCO₂ ≥ 400 or a PEEP of 45 cmH₂O was obtained. CPAP continuous positive airway pressure, OLA open lung approach [70]

Fig. 4

Components of volumetric capnography that can be used to personalize PEEP. a The three phases of capnography are: phase I contains CO₂-free gas from the previous tidal breath; phase II (S_II) is the steep slope contains CO₂ from the alveolar compartment and mixed with CO₂ in the airways from the previous breath; and phase III (S_III) is entirely CO₂ from alveoli and identifies the different time constants of CO₂ being released from the capillaries and moved out of the alveoli. VTCO₂,br is the volume of CO₂ removed in one breath (grey shaded area). b The black dot (A) identifies the midpoint of S_II which identifies the mean airway-alveolar interface from both diffusive and convective transports. To the left of (A) represents airway dead space (V _Daw) and to the right of (A) represents alveolar tidal volume (V_Talv). PaCO₂ = alveolar CO₂; PETCO₂ = end-tidal CO₂; PECO₂ = mixed-expired CO₂ [77]

Fig. 5

Lung ventilation during a decremental PEEP (15–0 cmH₂O) trial measured by electrical impedance tomography (EIT) in patients following cardiac surgery. The top row images from the cranial and the bottom row images from the caudal thoracic lung level. The optimal regional compliance was different between the cranial (10 and 5 cmH₂O) and caudal levels (15 and 10 cmH₂O) suggesting that no single optimal PEEP may exist for all lung levels [87]

Fig. 6

Use of the pressure/volume (P/V) curve to personalize PEEP. The shape of the P/V curve changes from normal (N) and differs greatly with emphysema (E) or acute pulmonary failure (APF). The P/V relationship during tidal ventilation is depicted in the shaded area with and without PEEP. RV regional volume at which alveoli collapse, FRC functional residual capacity, and TLC total lung capacity. Central drawing of alveoli size changes along the P/V curve [91]

Fig. 7

Pressure/volume (P/V) curve from an ARDS patient showing both the lower and upper inflection points (P _FLEX). The hypothesis is that the lower P _FLEX is the critical alveolar opening point and the upper P _FLEX the point at which alveoli begin to over-distend, however, this hypothesis has been challenged [97, 98]. In this patient, ventilation with a high tidal volume (Vt = 10 ml/kg plus PEEP_IDEAL = 15 cmH₂O) would cause over-distension since ventilation is well above the upper P _FLEX. Ventilation with low Vt and PEEP_IDEAL was below the upper P _FLEX. The calculated lung compliance was increased from 31.6 to 40 with low Vt ventilation [94]

Fig. 8

Pressure-time (P-t) curves demonstrating the concept of using stress index to personalize PEEP. Using the power equation P _L = a •t ^b + c, b describes the shape of the P-t curve. When b < 1, the shape of the curve is a downward concavity as compliance increases over time. When b > 1, the curve has an upward concavity as compliance decreases over time. When b = 1, the P-t curve is straight and compliance is constant. Adjusting tidal volume (Vt) and PEEP so that b = 1 produces minimal lung stress, if b < 1 would produce low-lung volume stress and b > 1 would cause high-lung volume stress [105]

Fig. 9

a Typical airway pressure release ventilation (APRV) airway pressure and flow curves. Correctly set APRV has a very brief duration at expiration (time at low pressure, T _Low) and extended inspiratory duration (time at high pressure, T _High) [109]. The T _High is ~90% of each breath. The two other ARPV settings are the pressure at inspiration (P _High) and at expiration (P _Low). P _High is set sufficiently high to recruit and open alveoli and P _Low is always set at 0 cmH₂O to facilitate expiratory flow. However, T _Low is sufficiently short such that end-expiratory pressure (P _Low) never reaches 0 cmH₂O identified by the tracheal pressure (green line) maintaining a level of PEEP. b This figure summarizes our novel method to maintain alveolar stability by adaptively adjusting the expiratory duration as directed by the expiratory flow curve. The rate of lung collapse is seen in the normal (slope 45°) and acutely injured lung (ARDS, slope 30°). ARDS causes a more rapid lung collapse due to decreased lung compliance. Our preliminary studies have shown that if the ratio of the peak expiratory flow (PEF, −60 L/min) to when we end expiratory flow (EEF, −45 L/min) (EEF/PEF) is equal to 75% that this expiratory duration (0.5 s) is sufficient to stabilize alveoli [40, 111]. The lung with ARDS collapses more rapidly such that the EEF/PEF-75% identifies an expiratory duration of 0.45 s necessary to stabilize alveoli. Although the EEF/PEF is fixed, the expiratory duration is not, but rather adaptive and will stabilize alveoli regardless of lung injury severity. Thus, this method of setting expiratory duration is adaptive to changes in lung pathophysiology and personalizes the mechanical breath to each individual patient