A 49-year-old woman with a history of chronic obstructive pulmonary disease and hepatitis C is being treated in the ICU with mechanical ventilation for acute respiratory distress syndrome (ARDS) secondary to COVID-19 pneumonia. The nurse calls because the ventilator alarm is sounding. At the bedside, the alarm shows peak pressure of 42 cm H2O. The chest is clear to auscultation and the nurse just suctioned the endotracheal tube with no secretions. The ventilator is set to assist control/volume control mode, with a tidal volume of 400 mL, respiratory rate of 16 breaths/min, a positive end-expiratory pressure (PEEP) of 20 cm H2O, and a fraction of inspired oxygen (FiO2) of 90%. The patient's ideal body weight (IBW) is 55 kg, and her body mass index is 17 kg/m2. Her heart rate is 88 beats/min, her blood pressure is 114/69 mm Hg, her respiratory rate is 18 breaths/min, and her oxygen saturation (SpO2) is 94%. The respiratory therapist reports that the patient has had elevated peak and plateau pressures. No auto-PEEP is detected and the patient is synchronous with the ventilator. A chest X-ray shows diffuse bilateral infiltrates, unchanged from before.
No effective therapies for ARDS exist other than supportive mechanical ventilation. Mechanical ventilation is a double-edged sword: Although necessary for respiratory support, when set improperly, it can cause a secondary ventilator-induced lung injury (VILI) that can increase the risk of mortality from ARDS. Thus, utilizing optimal ventilator settings, keeping the lungs open and protected, restoring lung homogeneity, and preventing VILI are the cornerstones of state-of-the-art mechanical ventilation, which is important for all hospital physicians to understand in the COVID-19 pandemic era.
The major processes that drive pulmonary ventilation are atmospheric pressure (Patm); the air pressure within the alveoli, called alveolar pressure (Palv); and the pressure within the pleural cavity, called intrapleural pressure (Ppl). The difference in pressure between intrapleural and intra-alveolar pressures is called transpulmonary pressure.
The mechanics of a respiratory cycle are determined by the interplay among three variables: flow, volume, and pressure. The difference in pressures drives pulmonary ventilation because air flows down a pressure gradient. Boyle's law describes the relationship between volume and pressure. The pressure of a gas is inversely proportional to its volume. If the volume of a space (like an alveolar space) increases, the alveolar pressure decreases (11. The process of breathing. Anatomy and Physiology. April 25, 2013. Accessed online. ). Figure 1 shows the pressure gradients within the thorax, which are key to understanding the basics of ventilation.
Monitoring lung mechanics
Monitoring respiratory mechanics is vital to decision making in respiratory care, including ventilator adjustments.
Plateau pressure is the equilibrium pressure reached at the end of inspiration. It has long been used as a surrogate for end-inspiratory alveolar distending pressure and is measured using the inspiratory hold maneuver, wherein gas flow in the airways is reduced to zero and airway pressure corresponds to alveolar pressure at full inspiration.
Peak pressure is the maximal pressure at the end of the proximal airway at the end of inspiration (Pao). Peak pressure is affected by changes in airway resistance. Airway pressure is typically displayed on the ventilator screen as a function of time (22. Hess DR. Respiratory mechanics in mechanically ventilated patients. Respir Care. 2014;59:1773-94. [PMID: 25336536]) (Figure 2).
When the ventilator alarm reports high peak airway pressures, it is crucial to distinguish between plateau and peak pressure to troubleshoot the problem. Peak pressure is equal to the flow × the resistance + plateau pressure. Thus, anything that changes resistance and flow through the airways, such as a mucus plug or bronchospasm, will alter the peak pressure but not the alveolar pressure (see Table). Any change in plateau pressure will also alter the peak pressure proportionately. The difference between peak airway pressure and plateau pressure should be less than 5 cm H2O.
Table. Common causes of elevation in peak and plateau pressures
|Causes of elevation only in peak pressure|
|Kinking of endotracheal tube|
|Obstruction of endotracheal tube such as mucus plug|
|Excessive airway secretions|
|Clogged heat moisture exchangers|
|Causes of elevation in both peak and plateau pressures|
|Acute respiratory distress syndrome|
|Abdominal compartment syndrome|
|Patient ventilator dyssynchrony|
It is suggested that plateau pressure be maintained at less than 30 cm H2O to minimize barotrauma. Patients with ARDS can have noncompliant lungs and elevated plateau pressure. This can be ameliorated to some degree by maintaining strict low tidal volume ventilation. Improvement in plateau pressure can be indicative of improvement in lung compliance.
The plateau pressure is indicative of the pressure needed to distend alveoli by overcoming the elastic recoil of the lung as well as the chest wall. Thus, it is not solely reflective of the alveolar distending pressure. A given plateau pressure can translate into different transpulmonary pressures depending on the chest wall compliance (33. Gattinoni L, Chiumello D, Carlesso E, et al. Bench-to-bedside review: chest wall elastance in acute lung injury/acute respiratory distress syndrome patients. Crit Care. 2004;8:350-5. [PMID: 15469597]).
For example, as shown in Figure 3, at a plateau pressure of 38 cm H2O in the lung, only 5 cm H2O pressure is used to counteract the chest wall elastance. The pressure at the alveolar level is 33 cm H2O. This is a high transpulmonary pressure, and the PEEP or tidal volume must be lowered to prevent VILI. Figure 4 shows a lung at the same plateau pressure of 38 cm H2O, but the transpulmonary pressure is only 18 cm H2O. This could be an example of a patient with obesity or circumferential burns, wherein a greater pressure of 20 cm H2O is needed to distend the chest wall. Since the transpulmonary pressure is only 18 cm H2O, there is no need to lower the PEEP in this case. Therefore, plateau pressure should be considered in the context of the resulting transpulmonary pressure.
Airway driving pressure has recently emerged as a key component for more precisely optimizing the delivered tidal volume and reducing VILI. Driving pressure is the ratio of tidal volume by total respiratory system compliance. Thus, driving pressure represents the tidal volume corrected for the patient's respiratory system compliance (44. Amato MB, Meade MO, Slutsky AS, et al. Driving pressure and survival in the acute respiratory distress syndrome. N Engl J Med. 2015;372:747-55. [PMID: 25693014], 55. Loring SH, Malhotra A. Driving pressure and respiratory mechanics in ARDS [Editorial]. N Engl J Med. 2015;372:776-7. [PMID: 25693019]). Driving pressure can be calculated at the bedside as plateau pressure minus PEEP. Driving pressure factors in respiratory system compliance, which is related to the total amount of available aerated lung volume; as such, it helps inform clinicians about the extent of lung stress/strain.
Determining compliance is the key to understanding individual lung pathology and is of utmost importance in managing mechanical ventilation. In some cases, continuous monitoring of lung compliance is crucial to discern the progression of disease and to guide ventilator adjustments.
The change in volume that occurs per unit change in the pressure of the system is called compliance. In simple terms, compliance refers to the distensibility of an elastic structure, such as the lung, or the ease with which an elastic structure can be stretched. Normal lung compliance is 70 to 100 mL/cm H2O or greater. In severe ARDS, compliance is usually in the range of 11 to 30 mL/cm H2O.
Lung compliance is measured as the change in lung volume divided by the change in transpulmonary pressure (compliance=ΔV/ ΔP). Transpulmonary pressure is the difference between the inside alveolar pressure and outside parietal pleura pressure and is responsible for distending the alveoli and maintaining alveolar inflation.
Lung compliance is inversely proportional to elastance. Elastance offers resistance to stretching forces. The elastic recoil of the chest wall also limits lung expansion at any applied pressure. Because the lung and the chest wall work together in tandem, they are measured in a parallel circuit (1/total compliance = 1/lung compliance + 1/chest wall compliance). The inspiratory hold maneuver yields plateau pressure and lung compliance. Both these numbers are displayed on the screen at the end of the maneuver.
Optimum ventilation strategy in ARDS
The ventilation strategy for ARDS has changed over the past decade. The focus has shifted from normalizing the arterial blood gas values with high tidal volume to a strategy that minimizes alveolar stretch due to excessive tidal volume (volutrauma), pressure (barotrauma), and the cyclic opening and collapse of diseased alveoli (atelectrauma). This approach aims to reduce inflammatory cytokine and neutrophil elastase production (biotrauma). The risk of volutrauma and barotrauma is addressed with reduced tidal volume and plateau pressure, whereas the atelectrauma may be avoided by recruitment maneuvers to open collapsed lung units and high PEEP.
Usually, ARDS patients have two types of regions in their lungs: relatively normally aerated, nondependent lung regions and relatively nonaerated, dependent lung regions. For this reason, the volume available for ventilation is smaller and described as “baby lung.” The solution to ventilate this “baby lung” and prevent overinflation of the relatively small, normally aerated regions is decreased tidal volume: 4 to 6 mL/kg of IBW (66. Brower RG, Matthay MA, Morris A, et al; Acute Respiratory Distress Syndrome Network. Ventilation with lower tidal volumes as compared with traditional tidal volumes for acute lung injury and the acute respiratory distress syndrome. N Engl J Med. 2000;342:1301-8. [PMID: 10793162], 77. Amato MB, Barbas CS, Medeiros DM, et al. Effect of a protective-ventilation strategy on mortality in the acute respiratory distress syndrome. N Engl J Med. 1998;338:347-54. [PMID: 9449727]).
The hallmark of ARDS is heterogeneous lung injury encompassing normal, collapsed, edematous, and unstable tissues. Therefore, the same tidal volume may lead to a completely different strain, depending on the actual amount of lung volume still open to ventilation, i.e., the size of the “baby lung.”
Driving pressure can be used as proxy for baby lung volume to help avoid VILI. As an example, imagine two patients with ARDS and an IBW of 80 kg are being ventilated with 6 mL/kg IBW, i.e., a tidal volume of 480 mL. If the resting available lung volume in one patient is only 300 mL, 6 mL/kg tidal volume/IBW would generate a strain of 480/300 (tidal volume/baby lung volume) or 1.6, thus causing hyperinflation and injury of lung units. However, if the other patient's baby lung volume were 800 mL, the induced strain would be 480/800 or 0.6.
The decrease in the available lung for ventilation manifests as a decrease in respiratory system compliance. Thus, normalizing tidal volume to lung compliance and using the ratio of tidal volume to compliance, also known as driving pressure, as an index to indicate the “functional” size of the lung are associated with improved outcomes and survival. In the above example, the first patient would have a high driving pressure and the second would have a low driving pressure. Functional lung size in ARDS is dynamic. Driving pressure can help represent the pressure that is actually applied to the lungs.
Attempts should be made to keep the driving pressure less than 13 to 15 cm H2O. For the sake of simplicity, it can be assumed that lower driving pressure corresponds to better lung compliance. Decreases in driving pressure owing to changes in ventilator settings are strongly associated with increased survival (44. Amato MB, Meade MO, Slutsky AS, et al. Driving pressure and survival in the acute respiratory distress syndrome. N Engl J Med. 2015;372:747-55. [PMID: 25693014], 55. Loring SH, Malhotra A. Driving pressure and respiratory mechanics in ARDS [Editorial]. N Engl J Med. 2015;372:776-7. [PMID: 25693019]).
The two main strategies to limit driving pressure during mechanical ventilation in ARDS patients are low tidal volume ventilation and appropriate PEEP. If PEEP is increased with constant tidal volume and driving pressure goes down, this indicates that there is an increase in lung compliance and that the higher PEEP is recruiting a greater number of nonaerated lung units. However, if incremental PEEP increases result in increased driving pressure, it suggests that increased PEEP is causing overdistention of the aerated lung units and, thus, lung injury. Therefore, titrating PEEP to reduce driving pressure may minimize further injury to the lung due to mechanical ventilation (88. Chiumello D, Carlesso E, Brioni M, et al. Airway driving pressure and lung stress in ARDS patients. Crit Care. 2016;20:276. [PMID: 27545828]). Changing the PEEP and observing the driving pressure is a quick bedside method to assess the balance of opening, closing, and overdistention during the mechanical breath.
PEEP improves arterial oxygenation by stabilizing end-expiratory lung volume and preventing alveolar collapse. The ability of PEEP to accomplish this goal depends on the lung's potential for recruitment. Alveolar volume loss and accumulation of alveolar and interstitial fluid, as occur in ARDS, reduce lung compliance and require higher pressure to inflate the alveoli. When there is a significant amount of “recruitable” lung, there is benefit from higher PEEP (99. Cressoni M, Cadringher P, Chiurazzi C, et al. Lung inhomogeneity in patients with acute respiratory distress syndrome. Am J Respir Crit Care Med. 2014;189:149-58. [PMID: 24261322]).
Beyond a certain applied pressure, PEEP application is not beneficial but rather detrimental, causing overdistension and barotrauma (Figure 5). Likewise, if the applied PEEP is below the lower inflection point, lung recruitment is suboptimal. In acute lung injury with relatively normal respiratory system compliance, the pressure/volume curve will not have a lower inflection point, since the majority of the alveoli are open. Recruitment potential of the lung is thus important, as is the appropriate selection of PEEP. Recruitability of the lung can be assessed at the bedside by using automated pressure/volume curve, a tool available in some ventilators. This is especially important to understand in COVID-19 pneumonia, which has variable presentations that are often times dynamic.
Lung heterogeneity, time constant, and auto-PEEP
The time constant represents the time required to fill 63% of the lung unit if a constant pressure is applied. It takes about five time constants to approximate the time required for completely filling or emptying a lung unit. Slow lung units, such as in chronic obstructive pulmonary disease (COPD), require more time to fill and empty. Time constant is important because lung diseases are often heterogeneous; compounding the problem further, different lung units may be in different time constants. One should be judicious in setting an appropriate inspiratory time in pressure-control ventilation and an adequate expiratory time (or I:E ratio) in obstructive lung disease. Incomplete emptying of the alveoli can result in an intrinsic PEEP, often referred to as auto-PEEP. Increasing the expiratory time, reducing the respiratory rate, or lowering the tidal volume can allow for complete emptying of the lungs. High auto-PEEP can be detrimental and can result in hemodynamic instability.
One of the most important processes in ARDS management is restoring lung homogeneity. The lung of a patient with ARDS is severely diseased and not a homogeneous structure anymore. Alveolar and interstitial edema affect the dependent posterior regions more than the ventral areas due to gravitational forces causing increased lung weight in these dorsal areas. The significantly variable degrees of ventilation and perfusion create a V/Q mismatch, causing hypoxia. The lung densities shift when a patient is repositioned from supine to prone; the lung weight and pulmonary edema move to the newly dependent part of the lung, which is the ventral region. PEEP acts as a counterforce to the compressing pressures from interstitial edema.
The isolated lung normally has a conical shape while the chest wall has a cylindrical shape, causing a shape-matching problem. Because the two structures have the same volume, the lung must expand its ventral regions more than the dorsal ones, and this condition results in a greater expansion of the nondependent ventral alveolar units or a lesser expansion of the dependent ones. In ARDS patients who are turned in the prone position, this effect of shape matching counterbalances gravity, reduced lung volume due to edema, and superimposed pressure in newly dorsal regions, allowing for more homogeneous distribution of lung weight and inflation of the lung (Figure 6).
The basis for possible effectiveness of proning in attenuating VILI is that the transpulmonary pressure, stress, and strain are more homogeneously distributed within the lung. In addition, prone positioning eliminates compression of the lungs by the heart and relieves the dependent lung area from abdominal pressure (1111. Koulouras V, Papathanakos G, Papathanasiou A, et al. Efficacy of prone position in acute respiratory distress syndrome patients: A pathophysiology-based review. World J Crit Care Med. 2016;5:121-36. [PMID: 27152255]). It's typically recommended for patients to be prone for 16 hours, followed by eight hours of supine position. Proning is less likely to show any benefit when done for short periods of time, such as two or three hours. Proning also works best in synergy with optimum ventilation strategies, such as adequate PEEP to allow for lung recruitment. Often, the hypoxia improves dramatically immediately after a patient is moved into prone position. However, one should not get too excited and quickly dial down the PEEP.
Paralytics are often used for up to 48 hours to improve hypoxia and patient-ventilator synchrony. In patients with severe ARDS, early administration of a neuromuscular blocking agent improved the adjusted 90-day survival and increased the time off the ventilator (1212. Papazian L, Forel JM, Gacouin A, et al; ACURASYS Study Investigators. Neuromuscular blockers in early acute respiratory distress syndrome. N Engl J Med. 2010;363:1107-16. [PMID: 20843245]).
The key to success with all of these interventions is to institute them in a timely fashion.
Ventilator-induced lung injury
VILI is a side effect of mechanical ventilation. Four biophysical mechanisms of VILI are widely accepted: volutrauma, barotrauma, atelectrauma, and stress concentration. VILI is due to excessive global/regional stress/strain and affects the relatively healthier regions of the lung since consolidated lung regions are not distended. Resulting biotrauma, that is, local and systemic inflammation and endothelial activation, may be thought of as the final common pathway that propagates VILI-mediated multiorgan failure (Figure 7) (1313. Gattinoni L, Carlesso E, Cadringher P, et al. Physical and biological triggers of ventilator-induced lung injury and its prevention. Eur Respir J Suppl. 2003;47:15s-25s. [PMID: 14621113], 1414. Carrasco Loza R, Villamizar Rodríguez G, Medel Fernández N. Ventilator-Induced Lung Injury (VILI) in Acute Respiratory Distress Syndrome (ARDS): Volutrauma and Molecular Effects. Open Respir Med J. 2015;9:112-9. [PMID: 26312103], 1515. Tonetti T, Vasques F, Rapetti F, et al. Driving pressure and mechanical power: new targets for VILI prevention. Ann Transl Med. 2017;5:286. [PMID: 28828361], 1616. Cressoni M, Chiurazzi C, Gotti M, et al. Lung inhomogeneities and time course of ventilator-induced mechanical injuries. Anesthesiology. 2015;123:618-27. [PMID: 26049554]).
In order to prevent VILI, transpulmonary pressure must be kept within the physiological range and uniformly distributed. Failure to consider transpulmonary pressure in a mechanically ventilated patient can lead to miscalculating VILI risk.
Low tidal volume ventilation is not the end game; it is the beginning of an optimal and protective mechanical ventilation strategy. Monitoring lung compliance and driving pressure further allows adjustment of tidal volume to the available lung units. PEEP may prevent VILI by keeping the lung open, thus reducing the regional stress/strain maldistribution. The prone position may attenuate VILI by increasing the homogeneity of transpulmonary pressure distribution. Simple bedside techniques and attention to lung mechanics can be used to further individualize mechanical ventilation, ameliorate VILI, and decrease mortality.
Back to the patient
The inspiratory hold maneuver demonstrated plateau pressure of 40 cm H2O and compliance of 19 mL/cm H2O. This resulted in a driving pressure of 20 cm H2O (plateau pressure − PEEP), which is significantly elevated and detrimental. The patient was also receiving a tidal volume of 400 mL, 7.27 mL/kg of her IBW. This was lowered to 330 mL (6 mL/kg IBW). The plateau pressure and driving pressure decreased to 37 H2O and 17 H2O, respectively, improvements although still elevated. Given her low actual body weight, her chest wall elastance was probably minimal. PEEP was reduced to 18 H2O, resulting in a plateau pressure of 34 H2O, a driving pressure of 16 H2O. and a compliance of 20 mL/cm H2O. After further reducing the PEEP to 16 H2O, a plateau pressure of 31 H2O, a driving pressure of 15 H2O, and compliance of 24 mL/cm H2O were achieved. Using driving pressure as a surrogate marker for transpulmonary pressure, the team optimized the tidal volume and PEEP, thus not only fixing the ventilator high-pressure alarm but also improving lung compliance and reducing the risk of VILI.