Introduction
Nowadays, it is recognized that patients receiving mechanical ventilation (MV) may actively contribute to the progression of lung injury through their own respiratory effort. This phenomenon, termed patient self-inflicted lung injury P-SILI, proposes that strong inspiratory efforts, patient-ventilator asynchronies, and markedly negative intrathoracic pressures can intensify injury in an already vulnerable lung parenchyma1.
Several studies have shown that neuromuscular blockade in patients with acute respiratory distress syndrome (ARDS) significantly improves oxygenation, likely by reducing spontaneous respiratory effort2. Complementary animal experiments have demonstrated that artificially increasing inspiratory effort through pharmacologic stimulation can induce severe lung injury, both clinically and histopathologically3.
The term “P-SILI” was introduced in 2017 to describe this phenomenon, highlighting the risk that a patient’s respiratory drive and effort may worsen lung injury-especially in severe ARDS and hypoxemic respiratory failure1.
In severe ARDS, these efforts may be difficult to control, and the complex patient-ventilator interaction can lead to regional overdistension, exaggerated alveolar recruitment, and heterogeneous ventilation distribution4–6.
This paradigm has transformed the understanding of ventilator-induced lung injury (VILI). It is now interpreted as the result of the interaction between mechanical support and spontaneous respiratory activity. Under this perspective, conventional protective ventilation may be insufficient to prevent injury progression. This has led to the exploration of ultraprotective MV (UMV) strategies, which further reduce ventilatory parameters (tidal volume < 6 mL/kg, plateau pressure < 25 cmH2O), often requiring extracorporeal CO2 removal (ECCO2R) to maintain adequate gas exchange7.
This narrative review aims to analyze the pathophysiology of P-SILI and evaluate the emerging role of UMV as a potential strategy to mitigate its deleterious effects.
P-SILI: epidemiology, pathophysiology, and identification
P-SILI results from excessive mechanical forces applied to a heterogeneous, vulnerable lung. Its epidemiology is not well established, as it represents a pathophysiological mechanism rather than an independent diagnosis. Most available studies are narrative reviews, animal or computational models, and clinical observations in contexts such as ARDS or COVID-198.
No global incidence rates have been identified, as P-SILI overlaps with other forms of lung injury and is not routinely diagnosed9. ARDS affects approximately 10% of critically ill patients in ICUs, with mortality of 30-50% pre-COVID-19, and P-SILI is considered a contributing factor in patients who generate vigorous respiratory efforts, though without specific quantification10.
Its central mechanisms can be divided into four interrelated components:
Increased lung stress and strain
During spontaneous inspiration, diaphragmatic contraction generates negative pleural pressure. This increases transpulmonary pressure (PL), the true determinant of stress. In ARDS lungs with reduced functional residual capacity, even normal or high effort can produce disproportionately high stress and strain in opened regions, leading to overdistension11. This parallels ventilator-induced volutrauma but is driven by the patient.
Worsening of pulmonary edema
Markedly negative pleural pressures significantly increase the transmural gradient across pulmonary capillaries, promoting edema formation. Increased venous return and right ventricular preload may further elevate capillary pressures, especially in patients with left-sided dysfunction12.
Pendelluft effect and atelectrauma
In heterogeneous lungs, rapid inspiratory effort may redistribute gas from long time-constant regions to short time-constant regions without net airflow at the airway opening. This causes overdistension of healthier units while collapsed units remain derecruited or worsen, perpetuating atelectrauma6.
Patient-ventilator asynchronies
Asynchronies such as ineffective effort, double triggering, and excessive effort worsen P-SILI. Double triggering results in two consecutive breaths, generating high effective tidal volume and peak pressure. Ineffective efforts increase the work of breathing without ventilation, contributing to fatigue and injury13.
Identification of P-SILI
Patients at greatest risk are those with acute respiratory failure and vigorous inspiratory efforts. Risk is amplified by lung heterogeneity, underlying inflammation, and non-invasive or assisted ventilation. Other risk factors include pulmonary hypertension, intense diaphragmatic effort, and pre-existing lung disease14.
Early detection depends on monitoring excessive respiratory effort. Esophageal pressure (Pes) and P0.1 are validated tools15.
Excessive negative pleural pressures increase PL, producing gas redistribution (Pendelluft), regional overdistension, endothelial/epithelial injury, and worsening lung damage16.
Pes permits estimation of PL and evaluation of compartmental mechanics. Proposed safety limits for dynamic PL are < 15-20 cmH2O9.
P0.1 correlates with respiratory drive and excessive inspiratory effort when > 3.5-4.0 cmH2O and identifies low effort when < 1.0 cmH2O, making it a practical tool to guide ventilation and prevent P-SILI15.
Ultraprotective invasive MV: a response to P-SILI?
Protective ventilation (tidal volume 6-8 mL/kg, plateau pressure < 30 cmH2O) became standard after the ARDSNet trial reduced mortality from 40% to 31%. However, in severe ARDS, mechanical power remained high (> 15 J/min), contributing to persistent VILI17.
If lung injury is driven by both ventilator and patient effort, a logical strategy is minimizing all mechanical forces-leading to the concept of UMV.
UMV uses very low tidal volumes (< 4-6 mL/kg predicted body weight) and plateau pressure < 25 cmH2O, aiming to reduce cyclic and static stress and limit volutrauma and P-SILI. By lowering mechanical power and energy applied to the lung, it seeks to interrupt lung injury progression7.
A 2007 Italian pilot study explored low tidal volume ventilation in ARDS and showed reduced inflammatory markers and improved compliance without significant hypercapnia. This highlighted the insufficiency of 6-8 mL/kg in heterogeneous lungs and encouraged further investigation of ultralow tidal volumes18.
Current clinical evidence
The systematic review and meta-analysis by Stommel et al. (2024) found that ECCO2R facilitates UMV by lowering PaCO2 and increasing pH. Although mechanical load decreases, no mortality or length-of-stay benefit was demonstrated, indicating a need for stronger evidence19.
In severe ARDS on extracorporeal membrane oxygenation (ECMO), the ECMOVENT study compared quasi-apneic ventilation (1 mL/kg) versus. pressure-controlled ventilation with ΔP 8 cmH2O and positive end-expiratory pressure 14 cmH2O. Both strategies significantly reduced mechanical load without differences in survival or ECMO duration20.
Similarly, Costa et al. (2024) found that extended lung protection with controlled ΔP (≤ 15 cmH2O) and respiratory drive modulation improved lung recovery in COVID-19 ARDS21.
Clinical implications and future perspectives
Identifying patients at risk of P-SILI is essential. Persistent asynchrony elevated respiratory drive, vigorous effort, and inadequate gas exchange despite protective MV may prompt the use of more aggressive strategies.
Recent literature supports the idea that UMV reduces mechanical injury and may improve recovery, but evidence on mortality remains inconclusive. Advanced monitoring-Pes, inspiratory effort, P0.1-may reduce P-SILI by tailoring interventions to underlying physiology22,23.
Conclusion
P-SILI represents a central component in acute lung injury pathophysiology, particularly in patients with preserved spontaneous breathing. Excessive effort may worsen injury through stress amplification, gas redistribution, and asynchrony. UMV facilitated by extracorporeal support represents a logical evolution of protective ventilation aimed at minimizing all mechanical aggression. Although high-level evidence on mortality impact is still emerging, its physiological basis is solid. A personalized approach guided by patient-ventilator interaction, P0.1, and Pes monitoring may improve outcomes, especially in severe ARDS.
Funding
The authors declare that they have not received funding.
Conflicts of interest
The authors declare no conflicts of interest.
Ethical considerations
Protection of human subjects and animals. The authors declare that no experiments on humans or animals were performed for this research.
Confidentiality, informed consent, and ethical approval. This study does not involve personal patient data, medical records, or biological samples, and does not require ethical approval. SAGER guidelines do not apply.
Declaration on the use of artificial intelligence. The authors declare that no generative artificial intelligence was used in the writing or creation of the content of this manuscript.
