Intensive Care Med

https://doi.org/10.1007/s00134-024-07366-y

WHAT’S NEW IN INTENSIVE CARE

Bedside‑available strategies to minimise

P‑SILI and VILI during ARDS
Oriol Roca1,2,3* , Irene Telias4,5,6 and Domenico L. Grieco7,8

© 2024 Springer-Verlag GmbH Germany, part of Springer Nature

Ventilator-induced (VILI) and patient-self-induced lung outcomes [3]. High-flow nasal oxygen (HFNO) reduces
injury (P-SILI) contribute to acute respiratory distress the risk of intubation in acute hypoxemic respiratory
syndrome (ARDS) progression in a relevant proportion failure (AHRF) [3]. CPAP and noninvasive ventilation,
of patients. VILI is a well-established concept encom- despite being applied worldwide, are not formally rec-
passing all deleterious effects of mechanical ventila- ommended but can be considered. Prolonged sessions of
tion (MV) [1]. It is a consequence of the excessive stress awake prone position may provide further advantages on
(pressure applied to the lungs) and strain (deformation lung protection in certain clinical circumstances.
induced by inflated volume) imposed by MV to the aer- Independently from the chosen technique, delayed
ated lung. VILI jeopardises patient’s outcome through intubation has been associated with worse outcomes
lung biotrauma, which induces systemic inflammation [4], possibly because of the occurrence of P-SILI dur-
and may contribute to multiorgan failure, a frequent ing treatment. The time of exposure to hypoxemia and
cause of death in ARDS patients. P-SILI is a more recent elevated respiratory rates (RR) during noninvasive sup-
concept and includes all the conditions in which sponta- port is proportional to respiratory system compliance
neous breathing in ARDS patients exhibiting high inspir- (Crs) deterioration, which makes it difficult to maintain
atory effort causes the inflation of large tidal volumes gas exchange, keeping driving pressure (ΔP) within safe
(Vt) yielding large transpulmonary pressure (PL) swings, limits after intubation [5]. Accordingly, patients’ moni-
increases in transvascular pressure favouring hydrostatic toring for early detection of noninvasive support failure
pulmonary oedema and regional overinflation through is essential during any treatment. Worsening Respira-
an intra-tidal redistribution of Vt from non-dependent to tory rate-OXygenation (ROX) index, defined as the ratio
dependent lung regions (i.e. pendelluft) [2]. between ­SpO2/FiO2 and respiratory rate (RR), and heart
We summarise the strategies that can potentially pre- rate, acidosis, consciousness, oxygenation, and respira-
vent the physiological mechanisms of both P-SILI and tory rate (HACOR) score, consisting of 5 different vari-
VILI at the bedside (Fig. 1). These are based on patient ables (heart rate, acidosis [pH], consciousness [GCS],
monitoring to provide personalised treatments tai- oxygenation, and RR) are reliable tools to identify HFNO
lored to physiological phenotypes. Most of these can be and continuous positive airway pressure (CPAP) (ROX)
applied without additional equipment and may be feasi- and noninvasive ventilation (NIV) (HACOR) failure [4].
ble in resource-limited settings. Another accurate predictor of NIV failure is the lack of
inspiratory effort reduction, which, however, requires
Safer use of noninvasive respiratory support oesophageal pressure monitoring [6]. This might not be
Different noninvasive respiratory support techniques feasible in all patients with AHRF, and alternative tech-
have distinct physiological effects that may influence niques to noninvasively estimate inspiratory effort are
being developed. Finally, clinical signs such as worsen-
ing ­PaO2/FiO2 ratio, respiratory rate, and dyspnoea are
*Correspondence: oroca@tauli.cat indicative of the patient’s deterioration and may prompt
1
Servei de Medicina Intensiva, Parc Taulí Hospital Universitari, Institut de the decision to intubate.
Recerca Part Taulí – I3PT, Parc del Taulí 1, 08028 Sabadell, Spain
Full author information is available at the end of the article
Safer use of controlled mechanical ventilation The use of prone position
Tidal volume and driving pressure In intubated patients, sessions of prone position for
Strain and stress are the major determinants of VILI. 12–18 h in moderate-to-severe ARDS patients convinc-
ΔP refers to the stress applied to the lung during tidal ingly reduce the risk of VILI and reverse right ventricle
ventilation. It is the ratio between Vt and Crs, which is failure and are a simple intervention to improve oxygena-
proportional to the size of the aerated lung. Patients tion [12]. To prevent VILI, the prone position should be
with high respiratory system elastance (Ers) (> 3 maintained regardless of the improvement in oxygena-
­cmH2O/(ml/kg)) are most likely to benefit from lower tion achieved.
Vt [9]. In contrast, allowing Vt > 6 mL/kg of predicted
body weight (PBW) in patients with low elastance PEEP and recruitability
allows less sedation and facilitates the transition to High PEEP prevents VILI only if it increases the volume
assisted ventilation. Therefore, a pragmatic approach of the aerated lung to an extent capable of sufficiently
could be starting with 6 mL/kg PBW, and then titrat- reducing dynamic strain (strain during tidal ventilation).
ing Vt to achieve a ΔP < 15 ­cmH2O. Significantly, PEEP This varies according to different degrees of recruitability.
below the airway opening pressure (AOP) can sub- High PEEP in patients with poor recruitability results in
stantially overestimate ΔP. Ongoing trials aiming baby lung overinflation and VILI. Recruitability is diffi-
to test whether titrating Vt limiting ΔP are underway cult to assess at the bedside. Computed tomography scan
(NCT05440851). Strain represents the deformation of is the gold standard, but may not always be clinically fea-
lung units during tidal ventilation, and it is defined as sible. Different bedside methods to assess recruitability
the ratio between Vt and the end-expiratory lung vol- have been described.
ume (the lung size at PEEP). Traditionally, Vt could be First, the recruitment-to-inflation (R/I) ratio can be
delivered using volume or pressure-controlled ventila- measured through a single-breath PEEP-reduction
tion, as no difference in outcomes has been observed manoeuvre with a low PEEP level above the AOP [13].
[7]. Moreover, it has been suggested that airway pres- Importantly, the R/I ratio accurately estimates the extent
sure release ventilation using time-controlled adaptive of PEEP-induced reduction in dynamic strain. Low R/I
ventilation may be even more protective in terms of ratio values (< 0.5–0.3) accurately identify patients with
VILI [8]. poor PEEP-induced recruitment and may benefit from
Finally, the extent of Vt reduction to minimise ΔP lower PEEP. Conversely, high PEEP might be considered
should, however, be balanced to the increase in RR in patients exhibiting high R/I values (> 0.5–0.7).
needed to ensure adequate alveolar ventilation, since Second, the hysteresis ratio, i.e. the maximal distance
high RR is itself injurious. Clinically, the combination between the inspiratory and expiratory limb weighted by
of Vt and RR that minimises the sum of [(4*ΔP) + RR] the maximal volume generated during a low-flow pres-
best limits the risk of death [10]. Mechanical power was sure–volume [14], and the Crs changes during a decre-
also described aiming to include the effect of RR and mental PEEP trial have also been shown to predict lung
PEEP on the effect of airway pressure and Vt in VILI recruitment.
development [11]. Despite being physiologically attrac- Some imaging techniques could be used. Electrical
tive, the main limitation of its use is that it is not easily impedance tomography monitoring during a decremen-
calculated at the bedside. tal PEEP trial allows identifying the level of PEEP that

(See figure on next page.)

Fig. 1 Summary of the different strategies that could be applied at the bedside in ARDS patients to minimise the risk of VILI and P-SILI. a Relation
of Vt with the product of four times driving pressure and respiratory rate at different levels of respiratory system compliance; b pressure–volumes
curves at different levels of PEEP to estimate the PEEP-induced recruited volume; c recruitment-to-inflation manoeuvre based on a single-breath
PEEP decrease and estimation of the exhaled tidal volume in patients with different levels of recruitability; d estimation of transpulmonary driving
using oesophageal pressure measurement; e decremental PEEP strategy with electrical impedance tomography to estimate the point with the bet-
ter balance between collapse and overdistension; f expiratory end-occlusion manoeuvre to estimate the occlusion pressure (Pocc); end-inspiratory
occlusion manoeuvre to estimate the airway driving pressure and the plateau pressure. HFNO high-flow nasal oxygen, CPAP continuous positive
airway pressure, NIV noninvasive ventilation, Vt tidal volume, ΔP driving pressure, RR respiratory rate, ERS elastance of the respiratory system, PBW
predicted body weight, Pplat plateau pressure, PL transpulmonary pressure, HME heat and moisture exchangers, PP prone position, PEEP positive
end-expiratory pressure, PV pressure–volume, EIT electrical impedance tomography, R/I recruitment to inflation, Pocc airway pressure generated by
respiratory muscle effort during an expiratory occlusion, ΔPLdyn dynamic transpulmonary driving pressure, FiO2 fraction of inspired oxygen
Fig. 1 (See legend on previous page.)
best compromises regional collapse and overdistension. manoeuvre can help assess inspiratory effort: 75% of the
This approach seems effective in setting PEEP based on deflection in airway pressure generated by the first effort
recruitability and confirmed that PEEP-induced changes during an expiratory hold accurately reflects inspiratory
in Crs (alone) are poorly informative of recruitment [15]. effort.
All these strategies may aid PEEP individualisation at the ΔP can also be measured in most patients dur-
bedside. Moreover, although the bedside assessment of ing assisted ventilation, and safe limits are consistent
biological subphenotypes is not feasible, hyperinflamma- with what was previously reported. Regarding PEEP, its
tory ARDS patients may benefit from higher PEEP [16]. increase reduces the inspiratory effort when there is an
Finally, recent ARDS guidelines recommend against increase in respiratory system compliance [21].
the use of prolonged recruitment manoeuvres (RM) [3]. Airway occlusion pressure (P0.1) is a measure of res-
However, the question of whether brief RM in highly piratory drive, and values > 3.5–4 cmH2O suggest inju-
recruitable patients or the application of sigh during rious inspiratory effort [22]. High respiratory drive and
pressure support ventilation may be associated with high inspiratory efforts can lead to asynchronies, such as
some benefit remains unanswered. breath stacking, that may be associated with lung injury
[23]
Transpulmonary pressure and end‑inspiratory lung stress Proper pressure support and sedation selection may
Transpulmonary pressure (PL) represents lung stress help modulate inspiratory effort and respiratory drive.
which, together with strain, is a major determinant Propofol and opioids mostly reduce the effort and respir-
of VILI [17]. Absolute values of oesophageal pressure atory rate, respectively.
(Pes) accurately reflect pleural pressure in the mid-to- Finally, phrenic nerve stimulation may facilitate the
dependent zones of the lung. This represents the lung transition to assisted breathing while decreasing the risk
superimposed pressure contributing to lung collapse of VILI, as it has been associated with positive effects on
[18]. End-expiratory PL (PLee) is calculated as PEEP— lung mechanics [24]. Similarly, prone position during
end-expiratory Pes during an expiratory pause. It has spontaneous breathing results in less effort-dependent
been shown that setting PEEP to obtain end-expiratory lung injury [25]
­PL close to 0 to avoid atelectrauma may improve survival
[19]. Take‑home message
Using ­PL, the static end-inspiratory lung stress could Integrative physiological monitoring of ARDS patients
be estimated by direct measurements or the elastance- may help bedside personalised treatments to minimise
derived method. The direct value of ΔPL can be obtained the risk of lung injury progression.
using the formula end-inspiratory PL (PLei) – PLee. The
elastance-derived method is based on the fact that,
Author details
because of a ventral-to-dorsal gravitational gradient, Pes 1
Servei de Medicina Intensiva, Parc Taulí Hospital Universitari, Institut de
does not reliably estimate pleural pressure value in non- Recerca Part Taulí – I3PT, Parc del Taulí 1, 08028 Sabadell, Spain. 2 Departament
dependent lung regions most susceptible to overdisten- de Medicina, Universitat Autònoma de Barcelona, Bellaterra, Spain. 3 Ciber
Enfermedades Respiratorias (Ciberes), Instituto de Salud Carlos III, Madrid,
tion. PLei can be estimated by plateau pressure (Pplat) Spain. 4 Keenan Research Centre for Biomedical Science, Li Ka Shing Knowl-
times the ratio of lung to respiratory system elastance edge Institute, St Michael’s Hospital, Unity Health Toronto, Toronto, Canada.
5
(EL/ERS) [18]. A safe limit for PLei may be 20–23 ­cmH2O. Interdepartmental Division of Critical Care Medicine, University of Toronto,
Toronto, Canada. 6 Division of Respirology, Department of Medicine, University
This may have important clinical implications: first, in Health Network and Sinai Health System, Toronto, Canada. 7 Department
patients with high EL/ERS ratio, Pplat of 28–30 c­ mH2O is of Emergency, Intensive Care Medicine and Anesthesia, Fondazione Policlinico
only apparently safe and should be reduced. In patients Universitario A. Gemelli IRCCS, Rome, Italy. 8 Department of Anesthesiology
and Intensive Care Medicine, Catholic University of the Sacred Heart, Rome,
with low EL/ERS, it could be safe to increase PEEP (if the Italy.
patient is recruitable) and tolerate Pplat exceeding 30
­cmH2O, with benefits on oxygenation [20]. Declarations

Conflicts of interest
Safer use of assisted modes and spontaneous OR reports receiving a research grant from Hamilton Medical AG and
Fihser&Paykel Healthcare Ltd, speaker fees from Hamilton Medical AG,
breathing Fisher&Paykel Healthcare Ltd, Aerogen Ltd, and non-financial research support
In ARDS, assisted ventilation should be resumed as soon from Timpel, and he is a minority stakeholder of Tesai Care SL, all outside the
as clinically possible. During assisted ventilation, inspira- submitted work. DLG has received speaking fees from Gilead, Intersurgical,
MSD and GE, and reports having received travel accommodation from Fisher
tory effort should be monitored to minimise the risk and Paykel. DLG discloses a research grant from GE. IT receives salary support
of P-SILI. Although there is no conclusive safe thresh- grant from the Canadian Institutes for Health Research in the form of a Post-
old, inspiratory effort should not exceed 10–15 c­ mH2O. Doctoral Fellowship Award, teaching honoraria from Medtronic, Getinge, and
consulting fees from MbMED SA, all outside the submitted work.
If oesophageal manometry is unavailable, a simple
Publisher’s Note in ARDS patients: why, when, how and for whom. Intensive Care Med
Springer Nature remains neutral with regard to jurisdictional claims in pub- 46:2385–2396
lished maps and institutional affiliations. 13. Chen L, Del Sorbo L, Grieco DL, Junhasavasdikul D, Rittayamai N, Soliman
I, Sklar MC, Rauseo M, Ferguson ND, Fan E, Richard JM, Brochard L (2020)
Received: 11 December 2023 Accepted: 17 February 2024 Potential for lung recruitment estimated by the recruitment-to-inflation
ratio in acute respiratory distress syndrome. A clinical trial. Am J Respir
Crit Care Med 201:178–187
14. Chiumello D, Arnal JM, Umbrello M, Cammaroto A, Formenti P, Mistraletti
G, Bolgiaghi L, Gotti M, Novotni D, Reidt S, Froio S, Coppola S (2020)
References Hysteresis and lung recruitment in acute respiratory distress syndrome
1. Slutsky AS, Ranieri VM (2013) Ventilator-induced lung injury. N Engl J Med patients: a CT scan study. Crit Care Med 48:1494–1502
369:2126–2136 15. Jonkman AH, Alcala GC, Pavlovsky B, Roca O, Spadaro S, Scaramuzzo G,
2. Brochard L, Slutsky A, Pesenti A (2017) Mechanical ventilation to minimize Chen L, Dianti J, Sousa MLA, Sklar MC, Piraino T, Ge H, Chen GQ, Zhou
progression of lung injury in acute respiratory failure. Am J Respir Crit JX, Li J, Goligher EC, Costa E, Mancebo J, Mauri T, Amato M, Brochard LJ
Care Med 195:438–442 (2023) Lung recruitment assessed by electrical impedance tomography
3. Grasselli G, Calfee CS, Camporota L, Poole D, Amato MBP, Antonelli M, (RECRUIT): a multicenter study of COVID-19 acute respiratory distress
Arabi YM, Baroncelli F, Beitler JR, Bellani G, Bellingan G, Blackwood B, Bos syndrome. Am J Respir Crit Care Med 208:25–38
LDJ, Brochard L, Brodie D, Burns KEA, Combes A, D’Arrigo S, De Backer 16. Calfee CS, Delucchi K, Parsons PE, Thompson BT, Ware LB, Matthay MA
D, Demoule A, Einav S, Fan E, Ferguson ND, Frat JP, Gattinoni L, Guérin C, (2014) Subphenotypes in acute respiratory distress syndrome: latent class
Herridge MS, Hodgson C, Hough CL, Jaber S, Juffermans NP, Karagiannidis analysis of data from two randomised controlled trials. Lancet Respir Med
C, Kesecioglu J, Kwizera A, Laffey JG, Mancebo J, Matthay MA, McAuley 2:611–620
DF, Mercat A, Meyer NJ, Moss M, Munshi L, Myatra SN, Ng Gong M, 17. Mauri T, Yoshida T, Bellani G, Goligher EC, Carteaux G, Rittayamai N, Mojoli
Papazian L, Patel BK, Pellegrini M, Perner A, Pesenti A, Piquilloud L, Qiu H, F, Chiumello D, Piquilloud L, Grasso S, Jubran A, Laghi F, Magder S, Pesenti
Ranieri MV, Riviello E, Slutsky AS, Stapleton RD, Summers C, Thompson TB, A, Loring S, Gattinoni L, Talmor D, Blanch L, Amato M, Chen L, Brochard L,
Valente Barbas CS, Villar J, Ware LB, Weiss B, Zampieri FG, Azoulay E, Cec- Mancebo J, Group PLpw (2016) Esophageal and transpulmonary pressure
coni M (2023) ESICM guidelines on acute respiratory distress syndrome: in the clinical setting: meaning, usefulness and perspectives. Intensive
definition, phenotyping and respiratory support strategies. Intensive Care Care Med 42:1360–1373
Med 49(7):727–759 18. Yoshida T, Amato MBP, Grieco DL, Chen L, Lima CAS, Roldan R, Morais
4. Grieco DL, Maggiore SM, Roca O, Spinelli E, Patel BK, Thille AW, Barbas CCA, Gomes S, Costa ELV, Cardoso PFG, Charbonney E, Richard JM,
CSV, de Acilu MG, Cutuli SL, Bongiovanni F, Amato M, Frat JP, Mauri T, Brochard L, Kavanagh BP (2018) Esophageal manometry and regional
Kress JP, Mancebo J, Antonelli M (2021) Non-invasive ventilatory support transpulmonary pressure in lung injury. Am J Respir Crit Care Med
and high-flow nasal oxygen as first-line treatment of acute hypoxemic 197:1018–1026
respiratory failure and ARDS. Intensive Care Med 47:851–866 19. Sarge T, Baedorf-Kassis E, Banner-Goodspeed V, Novack V, Loring SH,
5. Tsolaki VS, Zakynthinos GE, Mantzarlis KD, Deskata KV, Papadonta ME, Gong MN, Cook D, Talmor D, Beitler JR (2021) Effect of esophageal
Gerovasileiou ES, Manoulakas EE, Zakynthinos E, Pantazopoulos IN, Makris pressure-guided positive end-expiratory pressure on survival from acute
DA (2021) Driving pressure in COVID-19 acute respiratory distress syn- respiratory distress syndrome: a risk-based and mechanistic reanalysis of
drome is associated with respiratory distress duration before intubation. the EPVent-2 trial. Am J Respir Crit Care Med 204:1153–1163
Am J Respir Crit Care Med 204:478–481 20. Grasso S, Terragni P, Birocco A, Urbino R, Del Sorbo L, Filippini C, Mascia
6. Tonelli R, Fantini R, Tabbì L, Castaniere I, Pisani L, Pellegrino MR, Della L, Pesenti A, Zangrillo A, Gattinoni L, Ranieri VM (2012) ECMO criteria for
Casa G, D’Amico R, Girardis M, Nava S, Clini EM, Marchioni A (2020) Early influenza A (H1N1)-associated ARDS: role of transpulmonary pressure.
inspiratory effort assessment by esophageal manometry predicts non- Intensive Care Med 38:395–403
invasive ventilation outcome in de novo respiratory failure. a pilot study. 21. Dianti J, Fard S, Wong J, Chan TCY, Del Sorbo L, Fan E, Amato MBP,
Am J Respir Crit Care Med 202:558–567 Granton J, Burry L, Reid WD, Zhang B, Ratano D, Keshavjee S, Slutsky AS,
7. Rittayamai N, Katsios CM, Beloncle F, Friedrich JO, Mancebo J, Brochard Brochard LJ, Ferguson ND, Goligher EC (2022) Strategies for lung- and
L (2015) Pressure-controlled vs volume-controlled ventilation in acute diaphragm-protective ventilation in acute hypoxemic respiratory failure:
respiratory failure: a physiology-based narrative and systematic review. a physiological trial. Crit Care 26:259
Chest 148:34s0-355 22. Telias I, Junhasavasdikul D, Rittayamai N, Piquilloud L, Chen L, Ferguson
8. Camporota L, Rose L, Andrews PL, Nieman GF, Habashi NM (2024) Airway ND, Goligher EC, Brochard L (2020) Airway occlusion pressure as an esti-
pressure release ventilation for lung protection in acute respiratory mate of respiratory drive and inspiratory effort during assisted ventilation.
distress syndrome: an alternative way to recruit the lungs. Curr Opin Crit Am J Respir Crit Care Med 201:1086–1098
Care 30:76–84 23. Hashimoto H, Yoshida T, Firstiogusran AMF, Taenaka H, Nukiwa R, Koyama
9. Goligher EC, Costa ELV, Yarnell CJ, Brochard LJ, Stewart TE, Tomlinson G, Y, Uchiyama A, Fujino Y (2023) Asynchrony injures lung and diaphragm in
Brower RG, Slutsky AS, Amato MPB (2021) Effect of lowering tidal volume acute respiratory distress syndrome. Crit Care Med 51:e234–e242
on mortality in ARDS varies with respiratory system elastance. Am J 24. Parfait M, Rohrs E, Joussellin V, Mayaux J, Decavèle M, Reynolds S, Simi-
Respir Crit Care Med 203(11):1378–1385 lowski T, Demoule A, Dres M (2023) An initial investigation of diaphragm
10. Costa ELV, Slutsky A, Brochard LJ, Brower R, Serpa-Neto A, Cavalcanti AB, neurostimulation in patients with acute respiratory distress syndrome.
Mercat A, Meade M, Morais CCA, Goligher E, Carvalho CRR, Amato MBP Anesthesiology 140(3):483–494
(2021) Ventilatory variables and mechanical power in patients with acute 25. Yoshida T, Engelberts D, Chen H, Li X, Katira BH, Otulakowski G, Fujino Y
respiratory distress syndrome. Am J Respir Crit Care Med 204(3):303–311 (2022) Prone position minimizes the exacerbation of effort-dependent
11. Gattinoni L, Collino F, Camporota L (2023) Mechanical power: meaning, lung injury: exploring the mechanism in pigs and evaluating injury in
uses and limitations. Intensive Care Med 49:465–467 rabbits. Anesthesiology 136:779–791
12. Guérin C, Albert RK, Beitler J, Gattinoni L, Jaber S, Marini JJ, Munshi L,
Papazian L, Pesenti A, Vieillard-Baron A, Mancebo J (2020) Prone position