Abstract
Rationale
Mechanical power (MP) is a summary variable incorporating all causes of ventilator-induced-lung-injury (VILI). We expressed MP as the ratio between observed and normal expected values (MPratio).
Objective
To define a threshold value of MPratio leading to the development of VILI.
Methods
In a population of 82 healthy pigs, a threshold of MPratio for VILI, as assessed by histological variables and confirmed by using unsupervised cluster analysis was 4.5. The population was divided into two groups with MPratio above or below the threshold.
Measurements and main results
We measured physiological variables every six hours. At the end of the experiment, we measured lung weight and wet-to-dry ratio to quantify edema. Histological samples were analyzed for alveolar ruptures, inflammation, alveolar edema, atelectasis. An MPratio threshold of 4.5 was associated with worse injury, lung weight, wet-to-dry ratio and fluid balance (all p < 0.001). After 48 h, in the two MPratio clusters (above or below 4.5), respiratory system elastance, mean pulmonary artery pressure and physiological dead space differed by 32%, 36% and 22%, respectively (all p < 0.001), being worse in the high MPratio group. Also, the changes in driving pressure, lung elastance, pulmonary artery occlusion pressure, central venous pressure differed by 17%, 64%, 8%, 25%, respectively (all p < 0.001).
Limitations
The main limitation of this study is its retrospective design. In addition, the computation for the expected MP in pigs is based on arbitrary criteria. Different values of expected MP may change the absolute value of MP ratio but will not change the concept of the existence of an injury threshold.
Conclusions
The concept of MPratio is a physiological and intuitive way to quantify the risk of ventilator-induced lung injury. Our results suggest that a mechanical power ratio > 4.5 MPratio in healthy lungs subjected to 48 h of mechanical ventilation appears to be a threshold for the development of ventilator-induced lung injury, as indicated by the convergence of histological, physiological, and anatomical alterations. In humans and in lungs that are already injured, this threshold is likely to be different.
Similar content being viewed by others
Introduction
Over recent decades, research in mechanical ventilation has highlighted the potential harms associated with its use and described the mechanisms of injury through excessive pressure (barotrauma [1]), volume (volutrauma [2]), opening and closing of lung units (atelectrauma [3]), and subsequent inflammatory responses (biotrauma). Although these mechanisms collectively contribute to ventilator-induced lung injury (VILI), current ventilation strategies primarily focus on optimizing individual components of ventilation such as limiting plateau pressure [4], driving pressure [5], tidal volume and strain [6], or setting sufficient PEEP to obtain an “open-lung” approach [7]. In clinical practice, several co-factors play a role in the mortality associated with a specific ventilation strategy.
To fully understand the mechanism of VILI and quantify its effects, an experimental approach is required, in which the transition from healthy to injured lungs depends only on the applied mechanical ventilation. In recent years, we proposed the mechanical power (MP, i.e., the inflation energy delivered to the respiratory system per unit of time) as a comprehensive variable indicative of VILI development [8]. The concept of ergotrauma [9] was explored by varying tidal volume, PEEP, or respiratory rate across several animal studies [10,11,12].
However, a challenge with MP is its normalization, i.e., expressing MP per unit size of a biological variable. The same mechanical power, when applied to different animals, may be safe or harmful, depending on individual factors such as animal size, respiratory mechanics, or metabolic load. In analogy with the ventilatory ratio [13], we formulated the mechanical power ratio (MPratio) as the quotient of actual MP delivered, to that expected in normal pigs of comparable body weight under anesthesia.
An unresolved issue in VILI is its practical definition and quantification. The pathological and physiological manifestations of VILI (e.g., edema, alveolar/septal ruptures, microthrombosis, fibrosis, etc.) mirror the natural progression of unresolved acute respiratory distress syndrome (ARDS). Consequently, in clinical context, the presence of VILI is inferred from the difference in measurable outcomes (e.g., mortality) when different ventilatory strategies are employed (e.g., ARMA trial [5]). However, the exact mechanisms leading to increased mortality cannot be described or quantified.
In this study, we retrospectively calculated the MPratio in animals subjected to three distinct experiments of harmful mechanical ventilation designed to produce VILI by applying for 48 h an MP that ranged from 2.6 to 63.4 J min−1 (0.1–2.3 J min−1 kg−1) [10,11,12]. The aim was to explore, in previously healthy pigs, whether a specific MPratio threshold exists for VILI induction during 48 h of mechanical ventilation, and which physiological variables are associated with the anatomical and histological changes attributed to the development of VILI.
Material and methods
See Online Supplement for further details.
Study population
We included 82 female domestic pigs enrolled in previous experimental studies [10,11,12]. The pooled data from each experiment are summarized in Table 1. In summary the experiment 1 showed that the VILI was the same for a given mechanical power regardless of the variations of each individual component. In group 1 the mechanical power was reached primarily by increasing tidal volume, in group 2 by increasing respiratory rate and in group 3 by increasing PEEP. Experiment 2 was designed to identify a “safe value of mechanical power” below which no lung lesions could be observed. Experiment 3 was designed to determine if the retardation of expiratory flow in order to reduce the energy dissipation in the lung parenchyma during the expiratory phase was associated with a reduction in VILI. As shown in Table 1, the different experiments covered a wide range of ventilatory settings and mechanical power.
Mechanical power ratio
Mechanical power ratio was computed as the ratio of the actual mechanical power to the expected one. The mechanical power (actual and expected) was computed using the following formula [8]:
where MP is the mechanical power, RR is the respiratory rate, VT is the tidal volume, ELrs is the respiratory system elastance, I:E is the inspiratory/expiratory ratio, Raw is the airways resistance and PEEP is the positive end-expiratory pressure. The actual mechanical power was computed using the actual data measured during the experiment. The expected mechanical power was computed using the physiological normal values according to De Robertis et al. [14]: respiratory rate (20 breath min−1), tidal volume (10 mL kg−1), respiratory system elastance (0.75 cmH2O L−1 kg−1), I:E (1:2), airways resistance (3.9 cmH2O L−1 kg−1), PEEP (0 cmH2O).
The mechanical power ratio was than computed as the ratio of actual to expected MP:
Experimental protocol
The animal preparation, instrumentation, the number of variables and the timing of collection were the same in all three experiments. Under anesthesia, all animals, were instrumented with esophageal balloon, central venous, pulmonary, and femoral arterial and urinary catheters. The following variables were measured at baseline, 0.5 h after protocol initiation and thereafter every 6 h until the 48th hour.
Gas exchange
PO2, PCO2 and pH were measured both in the arterial and in mixed venous blood sampled from the pulmonary artery catheter. Venous admixture was calculated using the standard formula.
Respiratory system mechanics
We measured all standard indicators of respiratory system mechanics, including its chest wall and lung components. Aerated lung volumes (by helium gas dilution), elastances and lung stress were measured according to standard formulae.
Hemodynamics
We measured arterial, mixed venous, and wedge pressures (mmHg). Cardiac output was determined by transpulmonary thermodilution system and calculated by the reverse Fick’s method.
Gross pathology and histology assessment
The wet-to-dry ratio was measured in tissue samples taken immediately after death from liver, kidney, muscle, bowel (1 sample for each organ) and from the basal, middle and apical regions of both lungs (1 sample for each lung region). All samples were immediately weighed (wet) then stored to 50 °C for 24 h, then weighed again (dry). Wet-to-dry ratio was computed as the ratio between the wet tissue to the dry tissue weights.
The lungs were fixed in formalin; after 1 week, 20 samples (10 for each lung) were collected. Samples were first fixed in formalin 10% for 48 h and then paraffin embedded; histological sections of 3 microns thickness were stained by hematoxylin and eosin. Each slide was examined using a microscope at different magnifications.
Two independent pathologists, blinded to the experimental group assignment, classified each sample for the following alterations: alveolar ruptures, inflammation, alveolar edema, atelectasis, intra-alveolar hemorrhage, vascular congestion, perivascular edema, intravascular thrombi (see Fig. 1). The presence of given alterations was expressed according to the prevalence at which the alteration was observed in the field and score assigned as follow: for prevalence of 0–0.25 was assigned a score of 2, 0.25–0.5 a score of 4, 0.5–0.75 a score of 8 and 0.75–1 a score of 16. The non-linearity of the score was arbitrary decided before initiation of the study to underline the progressive increase of the lesions’ severity.
Statistical analysis
Continuous variables are reported as median [IQR], categorical variables as % (number). To assess the pattern of distribution of histological variables, the population was arbitrarily divided into deciles of MPratio each containing an equal number of animals. Possible clusters of histological variables related to VILI were identified by an unsupervised machine learning model, based on k-means clustering. The optimal number of clusters was selected according to the Silhouette method. To identify an MPratio threshold for VILI development, a logistic regression was performed with MPratio as predictor and clusters as outcome variables. Two-way analysis of variance (ANOVA) was applied to investigate the time-course of variables, with MPratio as between effect and time as within effect; post hoc tests were performed by pairwise Student’s T tests. A p value < 0.05 was considered as statistically significant. The analysis was performed using RStudio (RStudio Team (2020). RStudio: Integrated Development for R. RStudio, PBC, Boston, MA, URL http://www.rstudio.com/).
Mechanical power threshold finding process
To identify a possible mechanical power threshold for injury, we first divided the whole population into deciles of mechanical power. As shown in Fig. 2, alveolar ruptures, inflammation, alveolar edema and atelectasis increased markedly after the 5th decile of MPratio, i.e., MPratio > 4.46 (rounded to 4.5).
To confirm the graphical results, we performed a k-means clustering analysis of all the histological variables. This analysis identified two distinct injury clusters, as shown in Figure E1. The first cluster had significantly higher MPratio and higher lung histological scores, with greater alveolar edema and intra-alveolar hemorrhage, atelectasis, inflammation, septal ruptures and vascular congestion (alveolar damage group). The second cluster, which was exposed to lower MPratio, predominantly exhibited higher perivascular edema and intravascular thrombi (vascular damage group). The assignment to either of these histological clusters was associated to the MPratio (p < 0.001, Table E1). Logistic regression identified an MPratio > 4.5 as a discriminant value between the two clusters, which aligns with the upper limit value of the fifth decile of MPratio (see Table E2). Consequently, we divided the population into low (≤ 4.5) and high (> 4.5) MPratio groups according to this threshold.
Results
Pathological findings
In Figs. 2 and 3, we report the gross pathological findings measured in the MPratio deciles. Notably, the lung weight in the MPratio group higher than threshold of 4.5 was 68% greater compared to the lower MPratio group (Fig. 3A). A similar relationship was observed for the wet-to-dry ratio (Fig. 3B), and the fluid balance (Fig. 3C). Fluid balance was associated to the variations in lung weight (R2 = 0.61, p < 0.001, Figure E2, panel A) and histological VILI score (R2 = 0.32, p < 0.001, Figure E2, panel B, Table E3). The complete set of histological findings, including intra-alveolar hemorrhage, vascular congestion, perivascular edema, and intravascular thrombi, is reported in Table 2 as well as lungs’ weight and wet-to-dry ratio of lungs and other organs.
Physiological variables in high and low MPratio group at 0.5 h after the application of the experimental protocol
As shown in Table 3, ventilatory settings changed significantly from baseline after the application of the experimental protocol. Specifically, due to the protocol, minute ventilation, PEEP, mean airway pressure, plateau pressure, were notably higher in the high MPratio group compared to the low MPratio group. Similarly, gas exchange, respiratory mechanics and hemodynamic variables were different in the two groups, immediately after the implementation of the experimental protocol. Indeed, at 0.5 h, PaCO2 was lower and PaO2/FiO2 ratio was higher in the high MPratio group, while respiratory system elastance and lung stress were significantly higher in high MPratio group; as were most of hemodynamic variables. A summary of all respiratory mechanics, gas exchange and hemodynamic variables is presented in Table E3.
Physiological variables during time-course of the experiment
In Fig. 4, we display the time-course of three representative variables related to respiratory mechanics (respiratory system elastance, panel A), hemodynamics (mean pulmonary artery pressure, panel B) and gas exchange (physiological dead space, panel C). As shown, once the experimental phase began, all variables significantly and progressively deteriorated in the high MPratio group over the duration of the experiment. A summary of the time-course change of the most relevant pathophysiological variables is presented in Table 4. Of note, ventilatory settings (i.e., tidal volume, respiratory rate, PEEP and I:E ratio at 0.5 h) were maintained constant at the same values reported in Table 3. However, during the experiment, significant changes were observed in plateau pressure and MP, both of which increased to a greater extent in the high MPratio group. In addition, PaO2/FiO2, PaCO2 and physiological dead space significantly worsened in the high MPratio group; the same behavior was observed for the lung mechanics and for all hemodynamic variables. A complete summary of the variables is reported in Table E4.
Discussion
This experimental analysis investigates the role of mechanical power (MP) in generating VILI in large, healthy animals. Given the absence of pre-existing lung disease (healthy baseline), the progression observed over time can be attributed to mechanical ventilation, implying the development of VILI. This study has identified a specific power threshold that results in histologically confirmed lung injury.
The main results show that, with an applied MP ranging from 2.6 to 63.4 J min−1 (0.1–2.3 J min−1 kg-1), injury occurred when the applied MPratio exceeded approximately 4.5 times its normal expected value. This normal MP value was computed using data from De Robertis et al. [14] for domestic pigs, similar in weight to our population. The median value of normal expected MP was 0.094 J min−1 kg−1, close to the value expected in normal human (i.e., 6–7 J min−1 in a 70 kg individual) [15].
The two groups of animals defined as having a lower or higher MPratio than threshold of 4.5 differed considerably in terms of respiratory and hemodynamic physiology during the experiment. These differences were also associated with the higher fluid balance needed to maintain the hemodynamics in the group at higher MPratio [16]. Over time, from 0.5 to 48 h, key marker variables diverged between the two groups (Table E4) with the high MPratio group showing increased physiological dead space and worsened respiratory mechanics. These data are consistent with the appearance and worsening of structural lung lesions in that cohort. Despite increased histologically identified atelectasis, venous admixture decreased in the high MPratio group. This is not surprising, considering that atelectasis due to VILI is easily recruitable during inspiratory phase [17] and that oxygenation variables are not closely related to VILI-related outcome, as shown in the ARMA trial [6].
This study highlights the ambiguity in defining VILI, as it remains unclear which variables (anatomic, hemodynamics, mechanics, and gas exchange) are direct expressions of VILI or merely associated damage co-factors. Indeed, some authors have included the hemodynamic alterations and fluid balance under the VILI umbrella, while some others have not [18, 19]. Indeed, the use of terms as ventilator-induced lung injury or ventilation-induced lung injury or ventilator-associated lung injury reflect the lack of clarity of this concept. A possible model for VILI development during mechanical ventilation in healthy lungs [20] may consist of two sequences (Fig. 5).
Sequence 1: structural alterations
The gold standard for VILI should be the alveolar ruptures and extracellular matrix fragmentation due to the excessive MP, leading to increased dead space and lung elastance [20], as demonstrated in this study in the high MPratio group. Inflammation: alveolar ruptures and extracellular matrix fragmentation led to marked inflammation, with increased capillary permeability. This phenomenon may be tracked by changes in the level of inflammatory cytokines [21], and by a marked increase of inflammation as observed in histological samples of high MPratio group. Water retention/pulmonary hypertension/pulmonary edema/increased lung weight: Several variables, are associated with these phenomena. Water retention may be estimated by fluid balance, which was clearly more positive in the high MPratio group than in the low one. Lung weight (suggesting lung edema) was also markedly greater in the high MPratio group and was significantly associated with the fluid balance and with structural histological changes of the lung. It appears, therefore, that the formation of lung edema depends on both functional and structural changes of lung parenchyma. Compression atelectasis: lung edema and increased lung weight inevitably lead to compression atelectasis [22, 23]. The best way to measure it is the assessment of recruitability, as only atelectatic (i.e., compressed but empty) pulmonary units may be recruited. Unfortunately, we did not measure recruitability in our experiments. However, the frequency of atelectasis detected by histology was significantly higher in the high MPratio group. The consequent atelectrauma possibly contributed to enhance the inflammatory reaction and its consequences.
Sequence 2
It is possible that “harmful mechanical ventilation”, although not so severe as to induce structural changes, is sufficient to induce a marked hemodynamic response. Indeed, in our study we found that mechanical ventilation may be associated with increased pulmonary artery pressure. To support hemodynamics in the high MPratio group, fluid balance was markedly higher, with consequences similar to what is described in sequence 1. In essence, the difference between the two sequences is the lack of structural alteration, which selectively characterizes sequence 1. In our study, we had clear signs of hemodynamic compromise which appear more than a threshold-linked phenomenon, as they appeared proportional to the MP.
Limitations
Using healthy animals to study ventilator-induced lung injury (VILI) might be seen as a limitation. However, in our research, we consistently use healthy subjects to ensure that the only variable affecting lung damage is the mechanical ventilation per se, free from the confounding factors found in the “ARDS models”. In addition, over the course of our experimental model factors like inhomogeneity and stress raisers develop progressively, aligning the model more closely with the temporal evolution of the ARDS pathophysiology.
This study presents several other limitations primarily due to the retrospective design, which includes data from several experiments conducted at different times. The data derived from three distinct studies, each with potentially different use of fluid and vasopressors. This heterogeneity might have affected the results of the cluster analysis, potentially categorizing animals into groups based on the conditions of one larger study that employed significantly higher mechanical power and fluid balance. Additionally, the distribution of mechanical power ratio (MPratio) may have been more discrete than continuous due to the nature of the experimental design.
Another possible limitation may be the lack of comparisons of MP ratio to other possible “VILI markers” as driving pressure and the index proposed by Costa (4DP + RR) in which DP is the driving pressure and RR is the respiratory rate [24]. However, both driving pressure and frequency are included in the mechanical power equation and therefore these express the same elements of VILI. The direct comparison between mechanical power and driving pressure or 4DP + RR may be the focus of a different study but this may be inappropriate in an experimental model as the specific weighting of DP and RR may be different from the 4:1 found in human clinical trials.
However, we think that despite these limitations the results are valid. Variations in the expected MP do not compromise the validity of identifying a VILI threshold. The distribution of MP and MPratio seems to be near-continuous and well distributed across the range of MPratio (see Figure E4), and the fluid overload was the consequence of the high MP, rather than the cause.
The challenges of assessing VILI
These results and limitations reflect a longstanding debate in the understanding of VILI, which was already raised in the early descriptions of ARDS. Should the physiological hemodynamic response and its consequences (e.g., positive fluid balance and water retention due to the kidney response) be considered VILI in the absence of structural alterations?
Healthy lung
We argue that if one starts with healthy animals, whatever alterations we found were likely due to mechanical ventilation itself, as no prior inflammation, pulmonary hypertension or edema were present prior to its initiation. Accordingly, water retention, fluid balance and hemodynamic compromise should be considered part of VILI. Perhaps, this condition is better described by a term such as ventilator-induced injury, as most vital extrapulmonary organ systems, are indirectly compromised by mechanical ventilation.
Diseased lung
While the bulk of our results strongly suggest that a distinct MPratio greater than 4.5 causes VILI to become evident, this threshold cannot be, as such, translated to diseased lung and to human ARDS. Indeed, in diseased lung the damage related to the energy input should ideally be normalized to the size of the ventilatable lung, i.e., to the size of baby lung. While inflating the respiratory system requires a level of energy related to its mechanical characteristics, the capacity of the baby lung to receive it is less. The specific energy delivered per lung unit is an inverse function of baby lung size.
Conclusion
Our results suggest the existence of an MPratio threshold in healthy lungs.
Beyond this threshold, structural and functional changes consistent with Ventilator-Induced Lung Injury (VILI) occur, as indicated by the convergence of histological, physiological, and anatomical alterations. In lungs that are already injured, this threshold is likely to be different. This is due to the application of potentially damaging energy to a smaller aerated lung that is more vulnerable to strain. These findings contribute towards a correct understanding of the issue: distinguishing between the natural progression of the disease and the adverse impact of mechanical ventilation.
Availability of data and materials
The datasets used and/or analyzed during the current study are available from the corresponding authors on reasonable request.
Change history
12 September 2024
A Correction to this paper has been published: https://doi.org/10.1186/s40635-024-00666-z
References
Kumar A, Pontoppidan H, Falke KJ, Wilson RS, Laver MB (1973) Pulmonary barotrauma during mechanical ventilation. Crit Care Med 1(4):181–186. https://doi.org/10.1097/00003246-197307000-00001
Dreyfuss D, Soler P, Basset G, Saumon G (1988) High inflation pressure pulmonary edema. Respective effects of high airway pressure, high tidal volume, and positive end-expiratory pressure. Am Rev Respir Dis 137(5):1159–1164. https://doi.org/10.1164/ajrccm/137.5.1159
Tremblay L, Valenza F, Ribeiro SP, Li J, Slutsky AS (1997) Injurious ventilatory strategies increase cytokines and c-fos m-RNA expression in an isolated rat lung model. J Clin Invest 99(5):944–952. https://doi.org/10.1172/JCI119259
Tobin MJ (2001) Advances in mechanical ventilation. N Engl J Med 344(26):1986–1996. https://doi.org/10.1056/NEJM200106283442606
Amato MBP et al (2015) Driving pressure and survival in the acute respiratory distress syndrome. N Engl J Med 372(8):747–755. https://doi.org/10.1056/NEJMsa1410639
Acute Respiratory Distress Syndrome Network et al (2000) 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 342(18):1301–1308. https://doi.org/10.1056/NEJM200005043421801
Lachmann B (1992) Open up the lung and keep the lung open. Intensive Care Med 18(6):319–321. https://doi.org/10.1007/BF01694358
Gattinoni L et al (2016) Ventilator-related causes of lung injury: the mechanical power. Intensive Care Med 42(10):1567–1575. https://doi.org/10.1007/s00134-016-4505-2
Marini JJ (2019) Evolving concepts for safer ventilation. Crit Care 23(Suppl 1):114. https://doi.org/10.1186/s13054-019-2406-9
Vassalli F et al (2020) Does iso-mechanical power lead to iso-lung damage?: An experimental study in a porcine model. Anesthesiology 132(5):1126–1137. https://doi.org/10.1097/ALN.0000000000003189
Romitti F et al (2022) Mechanical power thresholds during mechanical ventilation: an experimental study. Physiol Rep 10(6):e15225. https://doi.org/10.14814/phy2.15225
Busana M et al (2022) Energy dissipation during expiration and ventilator-induced lung injury: an experimental animal study. J Appl Physiol (1985) 133(5):1212–1219. https://doi.org/10.1152/japplphysiol.00426.2022
Maj R et al (2023) Ventilatory ratio, dead space, and venous admixture in patients with acute respiratory distress syndrome. Br J Anaesth 130(3):360–367. https://doi.org/10.1016/j.bja.2022.10.035
De Robertis E, Liu JM, Blomquist S, Dahm PL, Thörne J, Jonson B (2001) Elastic properties of the lung and the chest wall in young and adult healthy pigs. Eur Respir J 17(4):703–711. https://doi.org/10.1183/09031936.01.17407030
Roussos C, Campbell EJM (1986) Respiratory muscle energetics. Comprehensive physiology. Wiley, New York, pp 481–509. https://doi.org/10.1002/cphy.cp030328
Gattarello S et al (2021) Role of fluid and sodium retention in experimental ventilator-induced lung injury. Front Physiol 12:743153. https://doi.org/10.3389/fphys.2021.743153
Cressoni M et al (2016) Mechanical power and development of ventilator-induced lung injury. Anesthesiology 124(5):1100–1108. https://doi.org/10.1097/ALN.0000000000001056
Katira BH (2019) Ventilator-induced lung injury: classic and novel concepts. Respir Care 64(6):629–637. https://doi.org/10.4187/respcare.07055
Gattinoni L, Collino F, Camporota L (2024) Ventilator induced lung injury: a case for a larger umbrella? Intensive Care Med 50(2):275–278. https://doi.org/10.1007/s00134-023-07296-1
Nuckton TJ et al (2002) Pulmonary dead-space fraction as a risk factor for death in the acute respiratory distress syndrome. N Engl J Med 346(17):1281–1286. https://doi.org/10.1056/NEJMoa012835
Ranieri VM et al (1999) Effect of mechanical ventilation on inflammatory mediators in patients with acute respiratory distress syndrome: a randomized controlled trial. JAMA 282(1):54–61. https://doi.org/10.1001/jama.282.1.54
Pelosi P, D’Andrea L, Vitale G, Pesenti A, Gattinoni L (1994) Vertical gradient of regional lung inflation in adult respiratory distress syndrome. Am J Respir Crit Care Med 149(1):8–13. https://doi.org/10.1164/ajrccm.149.1.8111603
Chiumello D et al (2016) Lung recruitment assessed by respiratory mechanics and computed tomography in patients with acute respiratory distress syndrome. What is the relationship? Am J Respir Crit Care Med 193(11):1254–1263. https://doi.org/10.1164/rccm.201507-1413OC
Costa ELV et al (2021) Ventilatory variables and mechanical power in patients with acute respiratory distress syndrome. Am J Respir Crit Care Med 204(3):303–311. https://doi.org/10.1164/rccm.202009-3467OC
Acknowledgements
We deeply thank ESTOR for its generous grant contribution, GENERAL ELECTRIC for providing the CARESCAPE ventilator and WERFEN for providing GEM5000 for blood gas analyses.
Funding
Open Access funding enabled and organized by Projekt DEAL. The support for this work has been provided from departmental sources, one unconditional research grant from Estor (Via Newton, 12-20016 Pero (MI)).
Author information
Authors and Affiliations
Contributions
Study concept and design: Gattinoni, D’Albo, Pozzi; acquisition, analysis or interpretation of data: D’Albo, Pozzi, Nicolardi, Galizia, Catozzi, Ghidoni, Donati, Romitti, Busana, Gattarello, Collino, Sonzogni; first drafting of manuscript-writing committee: Gattinoni, Marini, Camporota; critical revision for important intellectual content and final approval of manuscript: Marini, Meissner, Moerer, Sonzogni; statistical analysis: Pozzi, Camporota; administrative, technical or material support: Herrmann, Meissner, Moerer; study supervision: Gattinoni.
Corresponding author
Ethics declarations
Ethics approval and consent to participate
All experiments were approved by LAVES (Niedersächsisches Landesamt für Verbraucherschutz und Lebensmittelsicherheit, Projekte 18/2795, 19/3141) and they were carried out in a dedicated operating room in the animal facility within Göttingen Medicine University (UMG), Göttingen, Germany.
Consent for publication
Not applicable.
Competing interests
The authors declare that they have no competing interests.
Additional information
Publisher's Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Supplementary Information
Rights and permissions
Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.
About this article
Cite this article
D’Albo, R., Pozzi, T., Nicolardi, R.V. et al. Mechanical power ratio threshold for ventilator-induced lung injury. ICMx 12, 65 (2024). https://doi.org/10.1186/s40635-024-00649-0
Received:
Accepted:
Published:
DOI: https://doi.org/10.1186/s40635-024-00649-0