Acute respiratory distress syndrome (ARDS) is a common cause of acute respiratory failure and an important cause of death in critically ill ICU patients, especially SARS, severe avian influenza and severe H1N1. Pulmonary protective ventilation based on pathophysiological changes has been the main progress of mechanical ventilation in ARDS for more than a decade, especially in 2000 when the results of the ARDSnet study showed that small tidal volumes (Vt) could significantly reduce the mortality rate of ARDS, and pulmonary protective ventilation seemed to be the “panacea” to save ARDS. Unfortunately, from 2000 to the present, a series of RCT clinical studies have failed to obtain positive results for either high positive end-expiratory pressure (PEEP) or pulmonary resuscitation maneuvers (RM), and even the LOV study, which was perfect in terms of experimental design, used both low tidal volume, high PEEP, and repeated RM in the treatment group, but still failed to improve the prognosis of ARDS patients. This evidence-based medical evidence makes lung-protective mechanical ventilation in ARDS subject to unprecedented questions and challenges. The sharp opposition between the lung-protective ventilation strategy, which appears to be reasonable from the pathophysiological perspective of ARDS, and the results of evidence-based medical research compels us to systematically consider and seriously reflect on the current mechanical ventilation strategy in order to guide the clinical practice of ARDS mechanical ventilation.
I. Selection and implementation of individualized tidal volume
Patients with ARDS have different etiology, lesion type and extent of lesion involvement, different size and distribution of collapsed alveolar areas, resulting in lung heterogeneity and significant differences in the number and volume of normally ventilated alveoli in patients. Therefore, not all ARDS patients are suitable for a tidal volume of 6 ml/kg, how to achieve individualized selection of tidal volume?
1. It is more reasonable to set the tidal volume in combination with the plateau pressure. The airway plateau pressure can objectively reflect the intra-alveolar pressure. Several RCT studies recommended that the plateau pressure should be less than 30cmH2O during mechanical ventilation in ARDS to prevent alveolar overinflation, however, further studies found that the morbidity and mortality rate of ARDS patients decreased further with the reduction of plateau pressure, and even if the plateau pressure is already less than 30cmH2O, it is still necessary to consider whether patients need to further reduce the tidal volume to lower the plateau pressure. The current study concluded that for 6 ml/kg tidal volume, if the plateau pressure is still above 28-30 cm H2O, further reduction of tidal volume is needed. in the study of Terragni et al. with the goal of controlling the airway plateau pressure at 25-28 cm H2O, reducing the tidal volume to about 4 ml/kg was able to significantly reduce the inflammatory response in the lung and further reduce lung injury. Therefore, it may be more reasonable to set the tidal volume in combination with the plateau pressure.
2. Lung compliance guides the setting of tidal volume Lung compliance is also an important factor affecting the selection of tidal volume. Further analysis of the results of Deans’ study of small tidal volumes in ARDSnet revealed that for patients with ARDS whose lung compliance was not significantly reduced, ventilation with small tidal volumes (6 ml/kg) increased morbidity and mortality, while for patients with poor lung compliance, ventilation with small tidal volumes decreased morbidity and mortality. Brander et al. found that the better the pulmonary compliance, the greater the tidal volume required; the poorer the pulmonary compliance, the smaller the tidal volume required. Thus, pulmonary compliance becomes an important factor in determining the level of small tidal volumes.
Of course, due to the differences in thoracic lung volume and chest wall compliance in ARDS patients, there is no clear conversion relationship between tidal volume and compliance for the time being, which limits the clinical implementation. The monitoring of intrathoracic and trans-pulmonary pressures, which can exclude the influence of the chest wall, has been studied to prove its clinical value for the selection of PEEP, and its guiding value for the selection with tidal volume should be further studied.
3. The selection of tidal volume based on lung tissue stress and strain is more scientific The core of lung protective ventilation strategy is to prevent ventilator-associated lung injury (VILI). Recent studies have shown that the initiating factors for VILI are abnormal overall and local lung tissue stress and strain (Stress/Strain). tidal volumes can be set according to different FRCs in ARDS patients to control stress and strain within safe limits (currently the upper limit of stress is considered to be 27 cmH2O and upper limit of strain is 2). That is, patients with low FRC require small tidal volumes, while patients with relatively high FRC should probably be given larger tidal volumes. It can be seen that individualized setting of tidal volume is facilitated based on lung tissue stress and strain.
Lung tissue stress is a more direct reflection of altered lung tissue mechanics than platform pressure. By removing the effect of chest wall compliance, lung tissue stress directly reflects the pressure needed to overcome the elastic resistance of the lung tissue. It is more reasonable to set tidal volumes based on lung tissue stress and strain than platform pressures. With bedside monitoring of FRC and trans-pulmonary pressures now possible, setting tidal volumes based on lung tissue stress and strain offers clinicians a new way to do this.
4. Hypercapnia is no longer the main reason limiting the implementation of small tidal volumes Hypercapnia is the most common complication of small tidal volume ventilation and an important factor limiting the clinical application of small tidal volume ventilation. Although some studies have found that patients with ARDS can tolerate some degree of PaCO2 elevation, acute CO2 elevation leads to a range of pathophysiologic changes including cerebral and peripheral vasodilation, increased heart rate, elevated blood pressure and increased cardiac output. Increasing respiratory rate (40 breaths/min) and sodium bicarbonate supplementation (maximum dose of 20 mEq/h) may be considered to alleviate hypercapnia to some extent. However, on the basis of 6 ml/kg, if further reduction of tidal volume is needed, hypercapnia becomes a major obstacle.
Recent studies have shown that to further reduce tidal volume while avoiding hypercapnia, extracorporeal membrane lung (ECMO) can be used to remove CO2, and exciting results have been obtained. Of course, complex extracorporeal circulation techniques limit the use of ECMO in the salvage of ARDS. Recently, miniECMO has emerged to enable ICUs to perform ECMO at the bedside without an extracorporeal circulation pump, using the patient’s own arteriovenous pressure difference to achieve effective CO2 removal.
II. Pulmonary retensionability and pulmonary resuscitation
Pulmonary resuscitation is an important component of a protective lung strategy. Appropriate pulmonary retension pressure and timing can effectively correct hypoxemia and improve lung inhomogeneity; inappropriate pressure and timing may increase trans-pulmonary pressure, leading to alveolar hyperinflation, new inhomogeneity, and aggravated lung injury. Therefore, it is clearly inappropriate and prudent and possibly harmful to use a uniform pulmonary resuscitation technique for all ARDS patients.
1, a variety of factors affect ARDS lung retensibility The retensibility of the lung determines the lung retension conditions that should be used in ARDS. Pulmonary reducibility is the ability of lung tissue to be reopened and remain open. A variety of factors affect lung dilation in patients, including.
(1) The cause of ARDS: intrapulmonary causes, such as pneumonia, where there are collapsed alveoli filled with large amounts of inflammatory material or even solid lesions, have poor lung retensionability.
(2) Extent of solid lung tissue: solid lung tissue is difficult to be retensioned, and the greater the extent of solid lung tissue, the worse the retensibility of the lung tissue.
(3) Morphology of lung tissue: different morphological changes of lung tissue respond differently to the retension. Lung injury morphology is divided into focal and diffuse types. Studies have shown that diffuse lung injury has a good response to pulmonary resuscitation, and resuscitation can be actively implemented. In contrast, ARDS lungs with focal lesions show increased hyperinflation and poor retensionability after pulmonary resuscitation.
(4) Course of ARDS: The course of ARDS is roughly divided into the exudative, hyperplastic and fibrotic phases. The exudative phase responds relatively well to pulmonary dilation, while the fibrotic phase responds poorly to pulmonary dilation due to structural remodeling of lung tissue and interstitial fibrosis.
(5) Chest wall factors: Increased intra-abdominal pressure due to obesity and abdominal disease reduces the compliance of the patient’s chest wall, and such patients respond poorly to pulmonary resuscitation.
(6) Patient’s position: Some studies have found that prone position ventilation is less responsive to pulmonary resuscitation compared to supine position.
2. Judgment of pulmonary retensionability
Judgment of pulmonary dilation in ARDS patients is a prerequisite for proper implementation of pulmonary ventilation. The methods of determining pulmonary dilation include.
(1) Imaging examination Currently, CT is the common method to determine pulmonary dilation, and it is the gold standard to evaluate and measure pulmonary dilation. In addition, electronic impedance tomography (EIT) also has the ability to evaluate lung dilation. The P-V curve inspiratory branch morphology is predictive of lung tissue retension, and there are two different patterns of P-V curve inspiratory branches in ARDS patients. The other type of curve compliance gradually decreases with the increase of inspiratory pressure, which shows a downward curve bending. After increasing PEEP, the curve curved upward, the lung volume increased significantly at the same inspiratory pressure, suggesting high retensibility; the curve curved downward, the lung volume increased insignificantly, suggesting poor retensibility. (3) The hysteresis phenomenon of the static P-V curve can also reflect lung retensibility. The hysteresis phenomenon refers to the area between the inspiratory and expiratory branches of the P-V curve. Studies have confirmed that there is a significant positive correlation between the hysteresis of the P-V curve and alveolar retension, which can better predict the retensionability of lung tissue. (4) Gas exchange Oxygenation indexes are more readily available clinically, and whether oxygenation improves or not is also an important indicator to evaluate the effect of retension. However, the improvement of oxygenation is influenced by a variety of factors, and oxygenation to evaluate lung retensibility has limitations.
3. Pulmonary retensibility is used to guide the implementation of pulmonary resuscitation
Pulmonary retensibility can guide the implementation of pulmonary resuscitation. Pulmonary dilation is determined first in patients with ARDS, and then the decision is made whether to perform pulmonary resuscitation. Patients with high reducibility may be actively managed with a high level of PEEP, while patients with low reducibility may not be suitable for active reducibility or high PEEP, which may lead to alveolar hyperinflation and aggravate lung injury.
Gattinoni used chest CT scans to study pulmonary retensibility in 68 patients with ALI/ARDS and divided the patients into high and low retensible groups by the median value of retensible lung tissue (9%), and found that the severity of lung injury was significantly higher in the high retensible group than in the low retensible group, with a significantly higher mortality rate. The severity of lung injury was significantly higher in the high-reducible group than in the low-reducible group, and the morbidity and mortality rates were also significantly increased.
Selection of PEEP level
PEEP promotes the reopening of a large number of collapsed alveoli, increasing the number of effectively ventilated alveoli and increasing FRC, but if PEEP is too high, it may overinflate some normally ventilated lung tissues and aggravate lung injury, while if PEEP is too low, it is not enough to maintain the open state of alveoli and make them collapse.
The relationship between high PEEP levels and patient prognosis has been debated. 2004 ALVEOLI study showed that high PEEP did not improve the prognosis of ARDS patients. 2008 LOV study and Express study, both published simultaneously in JAMA, did not demonstrate that high PEEP improved the prognosis of ARDS. However, a recent Mata analysis showed that high PEEP (14-16 cmH2O) in ARDS patients reduced mortality, and that the higher the level of PEEP required, the more severe the patient’s condition. It is suggested that patients with severe disease, the required PEEP level is high and high PEEP improves the prognosis of patients with severe ARDS. It can be seen that the effect of PEEP on the prognosis of ARDS patients is still controversial.
How to choose the optimal PEEP still plagues the critical care physicians. From the purpose of improving oxygenation and preventing VILI, it is currently believed that the optimal PEEP should be able to maintain the opening of reopened alveoli while preventing alveolar hyperinflation in non-dependent areas, and from this perspective, the selection of PEEP should take into full consideration the following issues.
(1) The duration of ARDS disease Early and early response to PEEP is good, and patients with disease duration >7 days or more have poor response to PEEP.
(2) Pulmonary reducibility There is a significant difference in the response to PEEP between high and low pulmonary reducibility. For patients with low reducibility, high PEEP can cause hyperinflation of normally ventilated alveoli and aggravate lung injury. In contrast, for patients with high reversibility, a higher PEEP is required to maintain alveolar opening, which is beneficial to the patient.
(3) Heterogeneity of lung tissue lesions Patients with diffuse ARDS can use higher levels of PEEP, while patients with focal ARDS who use high PEEP will instead experience increased lung tissue hyperinflation. If the above factors are not fully considered, it is impossible to find the optimal PEEP for patients with ARDS.
In conclusion, both the selection of tidal volume and PEEP level and the implementation of pulmonary resuscitation maneuvers require individualized mechanical ventilation settings based on the pulmonary pathophysiological characteristics of each ARDS patient. The use of a uniform lung-protective ventilation strategy may be the main reason for the difficulty in obtaining positive results in RCT studies. Determining individualized mechanical ventilation treatment protocols for ARDS based on pathophysiological characteristics as a basis for designing more reasonable RCT study protocols is the only way to move from evidence-based medicine to clinical practice for pulmonary protective ventilation strategies in ARDS.