High risk of patient self-inflicted lung injury in COVID-19 with frequently encountered spontaneous breathing patterns: a computational modelling study

Abstract Background There is on-going controversy regarding the potential for increased respiratory effort to generate patient self-inflicted lung injury (P-SILI) in spontaneously breathing patients with COVID-19 acute hypoxaemic respiratory failure. However, direct clinical evidence linking increased inspiratory effort to lung injury is scarce. We adapted a computational simulator of cardiopulmonary pathophysiology to quantify the mechanical forces that could lead to P-SILI at different levels of respiratory effort. In accordance with recent data, the simulator parameters were manually adjusted to generate a population of 10 patients that recapitulate clinical features exhibited by certain COVID-19 patients, i.e., severe hypoxaemia combined with relatively well-preserved lung mechanics, being treated with supplemental oxygen. Results Simulations were conducted at tidal volumes (VT) and respiratory rates (RR) of 7 ml/kg and 14 breaths/min (representing normal respiratory effort) and at VT/RR of 7/20, 7/30, 10/14, 10/20 and 10/30 ml/kg / breaths/min. While oxygenation improved with higher respiratory efforts, significant increases in multiple indicators of the potential for lung injury were observed at all higher VT/RR combinations tested. Pleural pressure swing increased from 12.0 ± 0.3 cmH2O at baseline to 33.8 ± 0.4 cmH2O at VT/RR of 7 ml/kg/30 breaths/min and to 46.2 ± 0.5 cmH2O at 10 ml/kg/30 breaths/min. Transpulmonary pressure swing increased from 4.7 ± 0.1 cmH2O at baseline to 17.9 ± 0.3 cmH2O at VT/RR of 7 ml/kg/30 breaths/min and to 24.2 ± 0.3 cmH2O at 10 ml/kg/30 breaths/min. Total lung strain increased from 0.29 ± 0.006 at baseline to 0.65 ± 0.016 at 10 ml/kg/30 breaths/min. Mechanical power increased from 1.6 ± 0.1 J/min at baseline to 12.9 ± 0.2 J/min at VT/RR of 7 ml/kg/30 breaths/min, and to 24.9 ± 0.3 J/min at 10 ml/kg/30 breaths/min. Driving pressure increased from 7.7 ± 0.2 cmH2O at baseline to 19.6 ± 0.2 cmH2O at VT/RR of 7 ml/kg/30 breaths/min, and to 26.9 ± 0.3 cmH2O at 10 ml/kg/30 breaths/min. Conclusions Our results suggest that the forces generated by increased inspiratory effort commonly seen in COVID-19 acute hypoxaemic respiratory failure are comparable with those that have been associated with ventilator-induced lung injury during mechanical ventilation. Respiratory efforts in these patients should be carefully monitored and controlled to minimise the risk of lung injury.

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High risk of patient self-inflicted lung injury in COVID-19 with frequently encountered spontaneous breathing patterns: a computational modelling study

10.1101/2021.03.17.21253788 ◽

2021 ◽

Author(s):

Anup Das ◽

Liam Weaver ◽

Sina Saffaran ◽

Nadir Yehya ◽

Timothy E. Scott ◽

...

Keyword(s):

Lung Injury ◽

Computational Modelling ◽

Lung Compliance ◽

Inspiratory Effort ◽

Lung Mechanics ◽

Dynamic Strain ◽

Respiratory Effort ◽

Invasive Ventilation ◽

Breathing Patterns ◽

Spontaneously Breathing

There is ongoing controversy regarding the potential for increased respiratory effort to generate patient self-inflicted lung injury (P-SILI) in spontaneously breathing patients with COVID-19 acute respiratory failure. However, direct clinical evidence linking increased inspiratory effort to lung injury is scarce. We adapted a recently developed computational simulator that replicates distinctive features of COVID-19 pathophysiology to quantify the mechanical forces that could lead to P-SILI at different levels of respiratory effort. In accordance with recent data, the simulator was calibrated to represent a spontaneously breathing COVID-19 patient with severe hypoxaemia (SaO2 80.6%) and relatively well-preserved lung mechanics (lung compliance of 47.5 ml/cmH2O), being treated with supplemental oxygen (FiO2 = 100%). Simulations were conducted at tidal volumes (VT) and respiratory rates (RR) of 7 ml/kg and 14 breaths/min (representing normal respiratory effort) and at VT/RR of 15/14, 7/20, 15/20, 10/30, 12/30, 10/35, 12/35, 10/40, 12/40 ml/kg / breaths/min. Lung compliance was unaffected by increased VT but decreased significantly at higher RR. While oxygenation improved, significant increases in multiple indicators of the potential for lung injury were observed at all higher VT/RR combinations tested. Pleural pressure swing increased from 10.1 cmH2O at baseline to 30 cmH2O at VT/RR of 15 ml/kg / 20 breaths/min and to 54.6 cmH2O at 12 ml/kg / 40 breaths/min. Dynamic strain increased from 0.3 to 0.49 at VT/RR of 12 ml/kg / 30 breaths/min, and to 0.6 at 15 ml/kg / 20 breaths/min. Mechanical power increased from 7.83 J/min to 17.7 J/min at VT/RR of 7 ml/kg / 20 breaths/min, and to 240.5 7 J/min at 12 ml/kg / 40 breaths/min. Our results suggest that the forces generated during increased inspiratory effort in severe COVID-19 are compatible with the development of P-SILI. If conventional oxygen therapy or non-invasive ventilation is ineffective in reducing respiratory effort, control of driving and transpulmonary pressures with invasive ventilation may reduce the risk of P-SILI and allow time for the resolution of the underlying condition.

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Patient-Self Inflicted Lung Injury: A Practical Review

Journal of Clinical Medicine ◽

10.3390/jcm10122738 ◽

2021 ◽

Vol 10 (12) ◽

pp. 2738

Author(s):

Guillaume Carteaux ◽

Mélodie Parfait ◽

Margot Combet ◽

Anne-Fleur Haudebourg ◽

Samuel Tuffet ◽

...

Keyword(s):

Lung Injury ◽

Transpulmonary Pressure ◽

Inspiratory Effort ◽

Lung Damage ◽

Respiratory Drive ◽

Inhomogeneous Distribution ◽

Respiratory Effort ◽

Ventilatory Strategy ◽

Clinical Observations ◽

Severe Lung

Patients with severe lung injury usually have a high respiratory drive, resulting in intense inspiratory effort that may even worsen lung damage by several mechanisms gathered under the name “patient-self inflicted lung injury” (P-SILI). Even though no clinical study has yet demonstrated that a ventilatory strategy to limit the risk of P-SILI can improve the outcome, the concept of P-SILI relies on sound physiological reasoning, an accumulation of clinical observations and some consistent experimental data. In this review, we detail the main pathophysiological mechanisms by which the patient’s respiratory effort could become deleterious: excessive transpulmonary pressure resulting in over-distension; inhomogeneous distribution of transpulmonary pressure variations across the lung leading to cyclic opening/closing of nondependent regions and pendelluft phenomenon; increase in the transvascular pressure favoring the aggravation of pulmonary edema. We also describe potentially harmful patient-ventilator interactions. Finally, we discuss in a practical way how to detect in the clinical setting situations at risk for P-SILI and to what extent this recognition can help personalize the treatment strategy.

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Impact of Different Positive End-Expiratory Pressures on Lung Mechanics in the Setting of Moderately Elevated Intra-Abdominal Pressure and Acute Lung Injury in a Porcine Model

Journal of Clinical Medicine ◽

10.3390/jcm10020306 ◽

2021 ◽

Vol 10 (2) ◽

pp. 306

Author(s):

Mascha O. Fiedler ◽

Emilis Simeliunas ◽

B. Luise Deutsch ◽

Dovile Diktanaite ◽

Alexander Harms ◽

...

Keyword(s):

Acute Lung Injury ◽

Lung Injury ◽

Transpulmonary Pressure ◽

Lung Compliance ◽

Lung Mechanics ◽

Lung Injury Score ◽

Abdominal Pressure ◽

Injury Score ◽

Group A ◽

Over Time

The effects of a moderately elevated intra-abdominal pressure (IAP) on lung mechanics in acute respiratory distress syndrome (ARDS) have still not been fully analyzed. Moreover, the optimal positive end-expiratory pressure (PEEP) in elevated IAP and ARDS is unclear. In this paper, 18 pigs under general anesthesia received a double hit lung injury. After saline lung lavage and 2 h of injurious mechanical ventilation to induce an acute lung injury (ALI), an intra-abdominal balloon was filled until an IAP of 10 mmHg was generated. Animals were randomly assigned to one of three groups (group A = PEEP 5, B = PEEP 10 and C = PEEP 15 cmH2O) and ventilated for 6 h. We measured end-expiratory lung volume (EELV) per kg bodyweight, driving pressure (ΔP), transpulmonary pressure (ΔPL), static lung compliance (Cstat), oxygenation (P/F ratio) and cardiac index (CI). In group A, we found increases in ΔP (22 ± 1 vs. 28 ± 2 cmH2O; p = 0.006) and ΔPL (16 ± 1 vs. 22 ± 2 cmH2O; p = 0.007), with no change in EELV/kg (15 ± 1 vs. 14 ± 1 mL/kg) when comparing hours 0 and 6. In group B, there was no change in ΔP (26 ± 2 vs. 25 ± 2 cmH2O), ΔPL (19 ± 2 vs. 18 ± 2 cmH2O), Cstat (21 ± 3 vs. 21 ± 2 cmH2O/mL) or EELV/kg (12 ± 2 vs. 13 ± 3 mL/kg). ΔP and ΔPL were significantly lower after 6 h when comparing between group C and A (21 ± 1 vs. 28 ± 2 cmH2O; p = 0.020) and (14 ± 1 vs. 22 ± 2 cmH2O; p = 0.013)). The EELV/kg increased over time in group C (13 ± 1 vs. 19 ± 2 mL/kg; p = 0.034). The P/F ratio increased in all groups over time. CI decreased in groups B and C. The global lung injury score did not significantly differ between groups (A: 0.25 ± 0.05, B: 0.21 ± 0.02, C: 0.22 ± 0.03). In this model of ALI, elevated IAP, ΔP and ΔPL increased further over time in the group with a PEEP of 5 cmH2O applied over 6 h. This was not the case in the groups with a PEEP of 10 and 15 cmH2O. Although ΔP and ΔPL were significantly lower after 6 hours in group C compared to group A, we could not show significant differences in histological lung injury score.

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Faculty Opinions recommendation of Ventilation-induced lung injury exists in spontaneously breathing patients with acute respiratory failure: Yes.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.727195369.793572543 ◽

2020 ◽

Author(s):

Jeremy Beitler

Keyword(s):

Respiratory Failure ◽

Lung Injury ◽

Acute Respiratory Failure ◽

Spontaneously Breathing ◽

Ventilation Induced Lung Injury

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Effect of pressure-controlled ventilation-volume guaranteed mode combined with individualized positive end-expiratory pressure on respiratory mechanics, oxygenation and lung injury in patients undergoing laparoscopic surgery in Trendelenburg position

Journal of Clinical Monitoring and Computing ◽

10.1007/s10877-021-00750-9 ◽

2021 ◽

Author(s):

Jianli Li ◽

Saixian Ma ◽

Xiujie Chang ◽

Songxu Ju ◽

Meng Zhang ◽

...

Keyword(s):

Laparoscopic Surgery ◽

Lung Injury ◽

Respiratory Mechanics ◽

Lung Mechanics ◽

Trial Registry ◽

Positive End Expiratory Pressure ◽

Clinical Trial Registry ◽

Trendelenburg Position ◽

Pressure Controlled Ventilation ◽

Pressure Controlled

AbstractThe study aimed to investigate the efficacy of PCV-VG combined with individual PEEP during laparoscopic surgery in the Trendelenburg position. 120 patients were randomly divided into four groups: VF group (VCV plus 5cmH2O PEEP), PF group (PCV-VG plus 5cmH2O PEEP), VI group (VCV plus individual PEEP), and PI group (PCV-VG plus individual PEEP). Pmean, Ppeak, Cdyn, PaO2/FiO2, VD/VT, A-aDO2 and Qs/Qt were recorded at T1 (15 min after the induction of anesthesia), T2 (60 min after pneumoperitoneum), and T3 (5 min at the end of anesthesia). The CC16 and IL-6 were measured at T1 and T3. Our results showed that the Pmean was increased in VI and PI group, and the Ppeak was lower in PI group at T2. At T2 and T3, the Cdyn of PI group was higher than that in other groups, and PaO2/FiO2 was increased in PI group compared with VF and VI group. At T2 and T3, A-aDO2 of PI and PF group was reduced than that in other groups. The Qs/Qt was decreased in PI group compared with VF and VI group at T2 and T3. At T2, VD/VT in PI group was decreased than other groups. At T3, the concentration of CC16 in PI group was lower compared with other groups, and IL-6 level of PI group was decreased than that in VF and VI group. In conclusion, the patients who underwent laparoscopic surgery, PCV-VG combined with individual PEEP produced favorable lung mechanics and oxygenation, and thus reducing inflammatory response and lung injury.Clinical Trial registry: chictr.org. identifier: ChiCTR-2100044928

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Lung Contractive Change in Severe Acute Respiratory Failure Requiring Invasive Ventilation; A Comparison of Features Between Interstitial Lung Disease and Severe Infection

10.21203/rs.3.rs-155846/v1 ◽

2021 ◽

Author(s):

Kentaro Nagaoka ◽

Yu Yamashita ◽

Akira Oguma ◽

Hirokazu Kimura ◽

Kaoruko Shimizu ◽

...

Keyword(s):

Respiratory Failure ◽

Interstitial Lung Disease ◽

Lung Injury ◽

Acute Respiratory Failure ◽

Lung Disease ◽

Invasive Mechanical Ventilation ◽

Multivariate Logistic Regression Analysis ◽

Severe Infection ◽

Infection Group ◽

Radiological Features

Abstract Background: Generally, the incidence of irreversible lung injury is considered to be higher in acute respiratory failure due to interstitial lung disease (ILD), compared to those due to severe infection. However, those sub-phenotypes, which follow irreversible lung injury, remain poorly characterized. We aimed to examine their clinical and radiological features, in patients who could not withdraw from ventilation after receiving any treatment (defined as“irreversible respiratory failure”). Methods: Retrospective study including all patients receiving CT evaluation at onset and invasive mechanical ventilation for severe infection or acute ILD, who admitted our institution from April 2013 to May 2019. Participants were divided into Infection group and ILD group according to the dominant cause, and predictors of irreversible respiratory failure were examined among those subjects. In addition, we quantitatively evaluated the changes in lung region volumes and dispersion of grand glass opacity, using automated methods. Results: 31 patients were subdivided to ILD group, whereas 139 patients were subdivided to Infection group. Significantly more subjects in ILD group developed irreversible respiratory failure (n=22; 70.9%), compared to those in Infection group (n=27; 19.4%; p<0.001). With validation of radiological features in those subjects, distinct CT findings, including lung contractive change and non-edematous lung injury (NE-LI), were found in both groups. Lung contractive change was observed with 23 subjects in ILD group (74.2%) and 7 subjects in Infection group (5.0%). Among those, >10% lung volume reduction was confirmed by CT analysis with 19 subjects in ILD group and 4 subjects in Infection group. By multivariate logistic regression analysis, the following factors were found to be strong predictors of irreversible respiratory failure; lung contractive change (odds ratio [OR]=32.6; 95% confidence interval [CI], 7.1-150), NE-LI suspicious lesion (OR=13.3; 95% CI [2.9-59]), ILD-dominant respiratory failure (OR=18.4; 95% CI, 4.3-79), multidrug-resistant bacterial- or fungal-infection (OR=6.4; 95% CI, 1.3-31). Conclusions: We demonstrated the presence of sub-phenotypes in acute respiratory failure due to ILD and severe infection, which followed an irreversible course with distinctive radiological features including lung contractive changes.

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Lung mechanics are both dose and tidal volume dependant in LPS-induced lung injury

Respiratory Physiology & Neurobiology ◽

10.1016/j.resp.2009.06.008 ◽

2009 ◽

Vol 167 (3) ◽

pp. 333-340 ◽

Cited By ~ 18

Author(s):

Dani-Louise Dixon ◽

Hilde R. De Smet ◽

Andrew D. Bersten

Keyword(s):

Lung Injury ◽

Tidal Volume ◽

Lung Mechanics

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Two steps forward in bedside monitoring of lung mechanics: transpulmonary pressure and lung volume

Critical Care ◽

10.1186/cc12528 ◽

2013 ◽

Vol 17 (2) ◽

pp. 219 ◽

Cited By ~ 14

Author(s):

Gustavo A Cortes ◽

John J Marini

Keyword(s):

Lung Volume ◽

Transpulmonary Pressure ◽

Lung Mechanics ◽

Bedside Monitoring

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Crotoxin-Induced Mice Lung Impairment: Role of Nicotinic Acetylcholine Receptors and COX-Derived Prostanoids

Biomolecules ◽

10.3390/biom10050794 ◽

2020 ◽

Vol 10 (5) ◽

pp. 794

Author(s):

Marco Aurelio Sartim ◽

Camila O. S. Souza ◽

Cassiano Ricardo A. F. Diniz ◽

Vanessa M. B. da Fonseca ◽

Lucas O. Sousa ◽

...

Keyword(s):

Respiratory Failure ◽

Early Phase ◽

Late Phase ◽

Lung Mechanics ◽

Respiratory Compromise ◽

Nicotinic Acetylcholine ◽

Crotalus Durissus Terrificus ◽

Crotalus Durissus ◽

The Impact ◽

Lung Impairment

Respiratory compromise in Crotalus durissus terrificus (C.d.t.) snakebite is an important pathological condition. Considering that crotoxin (CTX), a phospholipase A2 from C.d.t. venom, is the main component of the venom, the present work investigated the toxin effects on respiratory failure. Lung mechanics, morphology and soluble markers were evaluated from Swiss male mice, and mechanism determined using drugs/inhibitors of eicosanoids biosynthesis pathway and autonomic nervous system. Acute respiratory failure was observed, with an early phase (within 2 h) characterized by enhanced presence of eicosanoids, including prostaglandin E2, that accounted for the increased vascular permeability in the lung. The alterations of early phase were inhibited by indomethacin. The late phase (peaked 12 h) was marked by neutrophil infiltration, presence of pro-inflammatory cytokines/chemokines, and morphological alterations characterized by alveolar septal thickening and bronchoconstriction. In addition, lung mechanical function was impaired, with decreased lung compliance and inspiratory capacity. Hexamethonium, a nicotinic acetylcholine receptor antagonist, hampered late phase damages indicating that CTX-induced lung impairment could be associated with cholinergic transmission. The findings reported herein highlight the impact of CTX on respiratory compromise, and introduce the use of nicotinic blockers and prostanoids biosynthesis inhibitors as possible symptomatic therapy to Crotalus durissus terrificus snakebite.

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