Prone Positioning May Increase Lung Overdistension in COVID-19-Induced ARDS

doi:10.21203/rs.3.rs-990841/v1

Download PDF

Research

Prone Positioning May Increase Lung Overdistension in COVID-19-Induced ARDS

https://doi.org/10.21203/rs.3.rs-990841/v1

This work is licensed under a CC BY 4.0 License

Version 1

posted

You are reading this older preprint version

Read the latest preprint version →

Background: Real-time effects of changing body position and positive end-expiratory pressure (PEEP) on regional lung overdistension and collapse in individual patients remain largely unknown and not timely monitored. The aim of this study was to individualize PEEP in supine and prone body positions seeking to reduce lung collapse and overdistension in mechanically ventilated patients with coronavirus disease (COVID-19)-induced acute respiratory distress syndrome (ARDS). We hypothesized that prone positioning with bedside titrated PEEP would provide attenuation of both overdistension and collapse.

Methods: In this prospective observational study, patients with COVID-19-induced ARDS under mechanical ventilation were included. We used electrical impedance tomography (EIT) with decremental PEEP titration algorithm (PEEP_{EIT-titration}), which provides information on regional lung overdistension and collapse, along with global respiratory system compliance, to individualize PEEP and body position. PEEP_{EIT-titration} in supine position straightaway followed by PEEP_{EIT-titration} in prone position were performed. Immediately before each PEEP_{EIT-titration}, the same lung recruitment maneuver was performed: 2 min of PEEP 24 cmH₂O and driving pressure of 15 cmH₂O.

Results: Forty-two PEEP_{EIT-titration} were performed in ten patients (21 pairs supine and prone positions). We have found larger % of overdistension along the PEEP titration in prone than supine position (P = 0.042). A larger % of collapse along the PEEP titration was found in supine than prone position (P = 0.037). A smaller respiratory system compliance was found in prone than supine position (P < 0.0005).

Conclusions: In patients with COVID-19-induced ARDS, prone body position, when compared with supine body position, decreased lung collapse at low PEEP levels, but increased lung overdistension at PEEP levels greater than 10 cm H₂O.

Trial registration number: NCT04460859

Anesthesiology & Pain Medicine

acute respiratory distress syndrome

COVID-19

electrical impedance tomography

mechanical ventilation

positive end-expiratory pressure

prone positioning

A majority of critically ill patients with coronavirus disease (COVID-19) develops acute respiratory distress syndrome (ARDS), needs mechanical ventilation for prolonged time, and exhibits high mortality [1, 2]. Prone positioning has been indicated in invasively ventilated patients with ARDS and COVID-19 [3]. In a recent evidence-based update of the Surviving Sepsis Campaign COVID-19 guidelines [4], prone ventilation over no prone ventilation is suggested as a weak recommendation for mechanically ventilated adults with COVID-19 and moderate-to-severe ARDS. On the management of COVID-19-induced ARDS, differently of the pre–COVID-19 era, prone position has been widely adopted, even before intubation in patients breathing spontaneously [5, 6]. For instance, seventy-six percent of COVID-19-induced ARDS patients from a cohort in Spain were proned (63% with mild ARDS) [7].

Beyond standard lung-protective ventilation regimes, intermittent prone positioning is suggested to improve gas exchange by reducing the ventilation and perfusion mismatching, but this has not been fully verified in clinical studies in this new disease entity [8]. Another piece of the COVID-19 puzzle [8] is the impact of delayed application of prone position [1]. In a cohort of 633 COVID-19 adult patients undergoing invasive mechanical ventilation [1], overall mortality was highest with non-resolution of hypoxemia and lack of oxygenation response to proning. In another cohort with 3988 critically ill patients with COVID-19 [2], positive end-expiratory pressure (PEEP) levels were higher than those reported for the management of moderate-to-severe ARDS in the pre–COVID-19 era and were an independent factor associated with high mortality.

Real-time effects of changing body position and PEEP on regional lung overdistension and collapse in individual patients remain largely unknown and not timely monitored. The aim of this study was to individualize PEEP in supine and prone body positions seeking to reduce lung collapse and overdistension. We hypothesized that prone positioning with bedside titrated PEEP would provide attenuation of both overdistension and collapse in mechanically ventilated patients with COVID-19-induced ARDS.

Patients with COVID-19-induced ARDS in the first days of mechanical ventilation were included. ARDS was defined according to the Berlin definition [9]. COVID-19 was confirmed by positive nasopharyngeal polymerase chain reaction for SARS-CoV-2. Patients were excluded in case of a contraindication to electrical impedance tomography (EIT): pacemaker, implantable defibrillator, skin lesion.

The design was a prospective observational study. The settings were the ICU of the Department of Anaesthesiology, Resuscitation and Intensive Medicine, First Faculty of Medicine, Charles University, General University Hospital in Prague, Czech Republic; and the ICU of the Pulmonology Division, Cardiopulmonary Department, Heart Institute, University of São Paulo, São Paulo, Brazil.

The study was approved by the Ethics Committee of the General University Hospital, Prague (833/20 S-IV), and by the Ethics Committee of the Heart Institute, University of São Paulo, São Paulo (CAAE: 30938720.8.0000.0068). Informed consent was obtained from all patients included in the study. We confirm that all the experiment protocol for involving humans was in accordance to guidelines of national/international/institutional or Declaration of Helsinki.

We used EIT with decremental PEEP titration algorithm (PEEP_{EIT−titration}) [10], which provides information on regional overdistension and collapse [11], along with global respiratory system compliance, to individualize PEEP and body position aiming to minimize ventilator-induced lung injury (VILI) mechanisms, namely collapse and overdistension. EIT is a noninvasive, radiation-free, real-time imaging method that measures regional changes in lung volumes. Lung collapse and overdistension percentages were determined by comparing each EIT pixel-compliance during PEEP_{EIT−titration} [11]. Each pixel-compliance was determined by dividing tidal impedance change by the variation in pressure during the respiratory cycle. Thereafter, overdistension was identified when, for a given pixel, aeration increased and compliance worsened. On the other hand, reversal of collapse was identified if aeration increased and compliance improved.

PEEP_{EIT−titration} in supine position straightaway followed by PEEP_{EIT−titration} in prone position were performed. The same lung fields were imaged in supine and prone body positions. During all the procedures, the patients were deeply sedated and under muscle paralysis.

Immediately before each PEEP_{EIT−titration}, the same lung recruitment maneuver was performed - 2 min of PEEP 24 cmH₂O and driving pressure of 15 cmH₂O - removing potential carry-over effects. The PEEP_{EIT−titration}, which started at a PEEP level of 24 cmH₂O, were performed with decremental PEEP steps of 2 cmH₂O each 30 s until reaching a lower PEEP level set by the clinician.

The EIT data of all PEEP_{EIT−titration} were analyzed to quantify the amounts of lung collapse and overdistension, and respiratory system compliance, at each PEEP step.

Statistical analysis

The Shapiro-Wilk test was used to test data for normality. The two-way repeated measures ANOVA was used to determine if there was a statistically significant interaction effect between our two within-subjects factors on our continuous dependent variable (i.e., whether a two-way interaction exists). Our continuous dependent variable was % overdistension or % collapse or respiratory system compliance. Our two independent variables were position (supine, prone) and PEEP [two within-subjects factors]. Simple and main effects were also tested where appropriated. The Bonferroni adjustment for multiple tests was applied for post hoc comparisons. The statistical analyses were conducted with SPSS (version 25; IBM Corp, IBM SPSS Statistics for Windows, Armonk, NY). Individual P values to indicate statistical tests’ significance are reported were relevant.

Forty-two PEEP_{EIT−titration} were performed in ten patients (21 pairs): supine followed by prone position. Table 1 shows the patients’ characteristics.

Overdistension: There was a statistically significant two-way interaction between body position (supine vs. prone) and PEEP on % of overdistension (P = 0.042; two-way repeated measures ANOVA). This indicates that the effect of supine position on % of overdistension is different to the effect of prone. That is, % of overdistension changed differently over PEEP levels depending on the position (Figure 1). We have found larger % of overdistension along the PEEP titration in prone than supine position. Additionally, when the simple main effects for position were tested, the following results were found: PEEP 20 (P = 0.056), PEEP 18 (P = 0.055), PEEP 16 (P = 0.034), and PEEP 14 cmH₂O (P = 0.040).

Collapse: There was a statistically significant two-way interaction between body position and PEEP on % of collapse (P = 0.037; two-way repeated measures ANOVA). This shows that the effect of supine position on % of collapse is different to the effect of prone, i.e. the amount of collapse changed differently over PEEP levels depending on the position (Figure 2). A larger % of collapse along the PEEP titration was found in supine than prone position. When the simple main effects for position were tested, the following results were found: PEEP 12 (P = 0.008), PEEP 10 (P = 0.016), and PEEP 6 cmH₂O (P = 0.033).

Compliance: There was a statistically significant two-way interaction between body position and PEEP on respiratory system compliance (P < 0.0005; two-way repeated measures ANOVA). This points out that the effect of supine position on respiratory system compliance is different to the effect of prone. A smaller respiratory system compliance was found in prone than supine position (Figure 3). Regarding the simple main effects for position, the following results were found: PEEP 20 (P < 0.0005), PEEP 18 (P < 0.0005), PEEP 16 (P < 0.0005), PEEP 14 (P = 0.002), PEEP 12 (P = 0.032), and PEEP 6 cmH₂O (P = 0.029); in these simple main effects for position analyzes, a smaller respiratory system compliance was found in prone position at the PEEP levels of 20, 18, 16, 14 and 12 cmH₂O.

Optimum PEEP: The optimum PEEP of each PEEP_{EIT−titration} was defined by the best compromise between pulmonary overdistension and collapse, i.e. the smallest sum of overdistension and collapse. The optimum PEEP was 13.7 ± 4.5 cmH₂O in supine position and 10.8 ± 4.3 cmH₂O in prone.

A major focus of mechanical ventilation for COVID-19-induced ARDS is the avoidance of VILI while facilitating gas exchange via lung-protective ventilation. This is a report of using EIT-based PEEP titration in supine and prone body positions to personalize body positioning and PEEP in adult patients with COVID-19-induced ARDS. During prone position, along with a smaller amount of collapse at low PEEP levels, we found a larger amount of overdistension at PEEP levels greater than 10 cm H₂O.

The primary indications for implementing prone ventilation in patients with ARDS are the need to improve oxygenation and the potential for prone position to reduce mortality [12]. It is usually assumed that in prone position there is less overdistension in nondependent lung regions and less cyclical airspace opening and closing in dependent regions [12]. Our findings suggest that in patients with COVID-19-induced ARDS these beneficial effects cannot be a priori assumed.

Hypoxemia disproportional to mechanics, lack of oxygenation response to proning, and poorly recruitable lungs with increased recruitability with alternating body position between supine and prone have been reported in COVID-19-induced ARDS [1]. A number of hypotheses have been proposed to explain such baffling hypoxemia, including SARS-CoV-2-specific effects on oxygen receptor chemosensitivity, reduced diffusion capacity, and loss of hypoxic vasoconstrictive mechanisms [8]. Many pathophysiological events may affect either lung perfusion or ventilation, all of which could lead to a ventilation/perfusion mismatch. Our findings suggest that, during prone, one of them can be a worsened ventilation/perfusion matching due to larger regional overdistension within more aerated lung regions and, consequently, more diversion of pulmonary blood flow away from these units, such effect surpassing the diminution of regional collapse within less aerated lung regions.

Our data underpin the importance of timely PEEP titrations tackling the dynamically changing phases of this disease [8]. They put forward the importance of monitoring and quantifying in real-time changes in overdistension and collapse - as well as the relevance of personalized PEEP adjustments - every time body positions are changed [10]. The recommendation of applying nonpersonalized low or high PEEP may lead to insufficient and/or excessive PEEP in terms of protection of VILI [8].

The response of respiratory system compliance to prone position is variable and complex [13]. Several observational studies reported that respiratory system compliance was unaltered or modestly decreased when turning from supine position to prone position in subjects with ARDS [14–19]. Other studies have reported improved respiratory system compliance upon being placed in prone position [20, 21], or after an extended period of prone position [14]. There is also evidence suggesting that patients with extrapulmonary sources of ARDS may be more likely to exhibit decreased respiratory system compliance when placed in prone position [16] possibly attributable to an accentuation of the characteristically decreased chest wall compliance found in that condition [22]. Our respiratory system compliance findings may suggest that, in prone position, the increase in lung overdistension predominated over the decrease of lung collapse. But we did not measure the changes in chest wall compliance. Anyway, altogether, our data point out that global respiratory mechanics alone does not provide enough information towards an individualization of body position and PEEP aiming at to reduce regional lung collapse and overdistension.

The main limitations include the small sample size, highly selected cohort, and the lack of repeated blood gases with PEEP titration (due to safety measures). Another limitation is the lack of esophageal pressure measurements during prone position, which may change the chest wall elastance. Larger series are needed to confirm the present findings.

In patients with COVID-19-induced ARDS, prone body position, when compared with supine body position, decreased lung collapse at low PEEP levels, but increased lung overdistension at PEEP levels greater than 10 cm H₂O.

COVID-19: Coronavirus disease

ARDS: Acute respiratory distress syndrome

ICU: Intensive care unit

PEEP: Positive end-expiratory pressure

F_IO₂: Fraction of inspired oxygen

PaO₂: Arterial oxygen partial pressure

PaO₂/F_IO₂: Partial pressure of arterial oxygen ratio

P_L: Transpulmonary pressure (P_L = airways pressure − pleural pressure)

EIT: Electrical impedance tomography

PEEP_EITtitration: PEEP titration algorithm using EIT

VILI: Ventilator-induced lung injury

Ethics approval and consent to participate

The study was approved by the Ethics Committee of the General University Hospital, Prague (833/20 S-IV), and by the Ethics Committee of the Heart Institute, University of Sao Paulo, Sao Paulo (CAAE: 30938720.8.0000.0068). Informed consent was obtained from all patients included in the study. We confirm that all the experiment protocol for involving humans was in accordance to guidelines of national/international/institutional or Declaration of Helsinki.

Consent for publication

Not applicable. Our manuscript does not contain any individual person’s data in any form (including individual details, images or videos).

Availability of data and materials

The data are with the authors and will be available upon reasonable request. The data is available from the corresponding author: Joao Batista Borges.

Competing interests

The authors report no conflict of interests.

Funding

This work was financially supported by Technology Agency of the Czech Republic (FW 01010679) and Progres 206–041. The funding has no influence in study design, data analysis or publication.

Authors’ contributions

MM, MO, JBB, GCA, DH, LT and MA collected the data. JBB and GCA analyzed the patient data and drafted the manuscript. MM, MO, GCA, EK, MA and OK developed the concept. MM, MO, JBB, GCA, EK and MA interpreted the data.

All authors revised the manuscript critically. All authors read and approved the final manuscript.

Acknowledgements

Not applicable.

Patel BV, Haar S, Handslip R, Auepanwiriyakul C, Lee TM, Patel S, Harston JA, Hosking-Jervis F, Kelly D, Sanderson B, et al: Natural history, trajectory, and management of mechanically ventilated COVID-19 patients in the United Kingdom. Intensive Care Med 2021.
Grasselli G, Greco M, Zanella A, Albano G, Antonelli M, Bellani G, Bonanomi E, Cabrini L, Carlesso E, Castelli G, et al: Risk Factors Associated With Mortality Among Patients With COVID-19 in Intensive Care Units in Lombardy, Italy. JAMA Intern Med 2020, 180:1345-1355.
Nasa P, Azoulay E, Khanna AK, Jain R, Gupta S, Javeri Y, Juneja D, Rangappa P, Sundararajan K, Alhazzani W, et al: Expert consensus statements for the management of COVID-19-related acute respiratory failure using a Delphi method. Crit Care 2021, 25:106.
Alhazzani W, Evans L, Alshamsi F, Moller MH, Ostermann M, Prescott HC, Arabi YM, Loeb M, Ng Gong M, Fan E, et al: Surviving Sepsis Campaign Guidelines on the Management of Adults With Coronavirus Disease 2019 (COVID-19) in the ICU: First Update. Crit Care Med 2021, 49:e219-e234.
Ferrando C, Mellado-Artigas R, Gea A, Arruti E, Aldecoa C, Adalia R, Ramasco F, Monedero P, Maseda E, Tamayo G, et al: Awake prone positioning does not reduce the risk of intubation in COVID-19 treated with high-flow nasal oxygen therapy: a multicenter, adjusted cohort study. Crit Care 2020, 24:597.
Coppo A, Bellani G, Winterton D, Di Pierro M, Soria A, Faverio P, Cairo M, Mori S, Messinesi G, Contro E, et al: Feasibility and physiological effects of prone positioning in non-intubated patients with acute respiratory failure due to COVID-19 (PRON-COVID): a prospective cohort study. Lancet Respir Med 2020, 8:765-774.
Ferrando C, Suarez-Sipmann F, Mellado-Artigas R, Hernandez M, Gea A, Arruti E, Aldecoa C, Martinez-Palli G, Martinez-Gonzalez MA, Slutsky AS, et al: Clinical features, ventilatory management, and outcome of ARDS caused by COVID-19 are similar to other causes of ARDS. Intensive Care Med 2020, 46:2200-2211.
Osuchowski MF, Winkler MS, Skirecki T, Cajander S, Shankar-Hari M, Lachmann G, Monneret G, Venet F, Bauer M, Brunkhorst FM, et al: The COVID-19 puzzle: deciphering pathophysiology and phenotypes of a new disease entity. Lancet Respir Med 2021.
Force ADT, Ranieri VM, Rubenfeld GD, Thompson BT, Ferguson ND, Caldwell E, Fan E, Camporota L, Slutsky AS: Acute respiratory distress syndrome: the Berlin Definition. JAMA 2012, 307:2526-2533.
Mlcek M, Otahal M, Borges JB, Alcala GC, Hladik D, Kuriscak E, Tejkl L, Amato M, Kittnar O: Targeted lateral positioning decreases lung collapse and overdistension in COVID-19-associated ARDS. BMC Pulm Med 2021, 21:133.
Costa EL, Borges JB, Melo A, Suarez-Sipmann F, Toufen C, Jr., Bohm SH, Amato MB: Bedside estimation of recruitable alveolar collapse and hyperdistension by electrical impedance tomography. Intensive Care Med 2009, 35:1132-1137.
Guerin C, Albert RK, Beitler J, Gattinoni L, Jaber S, Marini JJ, Munshi L, Papazian L, Pesenti A, Vieillard-Baron A, Mancebo J: Prone position in ARDS patients: why, when, how and for whom. Intensive Care Med 2020, 46:2385-2396.
Kallet RH: A Comprehensive Review of Prone Position in ARDS. Respir Care 2015, 60:1660-1687.
Fridrich P, Krafft P, Hochleuthner H, Mauritz W: The effects of long-term prone positioning in patients with trauma-induced adult respiratory distress syndrome. Anesth Analg 1996, 83:1206-1211.
Johannigman JA, Davis K, Jr., Miller SL, Campbell RS, Luchette FA, Frame SB, Branson RD: Prone positioning and inhaled nitric oxide: synergistic therapies for acute respiratory distress syndrome. J Trauma 2001, 50:589-595; discussion 595-586.
Lim CM, Kim EK, Lee JS, Shim TS, Lee SD, Koh Y, Kim WS, Kim DS, Kim WD: Comparison of the response to the prone position between pulmonary and extrapulmonary acute respiratory distress syndrome. Intensive Care Med 2001, 27:477-485.
Stocker R, Neff T, Stein S, Ecknauer E, Trentz O, Russi E: Prone postioning and low-volume pressure-limited ventilation improve survival in patients with severe ARDS. Chest 1997, 111:1008-1017.
Jozwiak M, Teboul JL, Anguel N, Persichini R, Silva S, Chemla D, Richard C, Monnet X: Beneficial hemodynamic effects of prone positioning in patients with acute respiratory distress syndrome. Am J Respir Crit Care Med 2013, 188:1428-1433.
Offner PJ, Haenel JB, Moore EE, Biffl WL, Franciose RJ, Burch JM: Complications of prone ventilation in patients with multisystem trauma with fulminant acute respiratory distress syndrome. J Trauma 2000, 48:224-228.
Servillo G, Roupie E, De Robertis E, Rossano F, Brochard L, Lemaire F, Tufano R: Effects of ventilation in ventral decubitus position on respiratory mechanics in adult respiratory distress syndrome. Intensive Care Med 1997, 23:1219-1224.
Blanch L, Mancebo J, Perez M, Martinez M, Mas A, Betbese AJ, Joseph D, Ballus J, Lucangelo U, Bak E: Short-term effects of prone position in critically ill patients with acute respiratory distress syndrome. Intensive Care Med 1997, 23:1033-1039.
Kallet RH, Katz JA: Respiratory system mechanics in acute respiratory distress syndrome. Respir Care Clin N Am 2003, 9:297-319.

Table 1: Patients’ characteristics.

Definition of abbreviations: BMI = body mass index; DP = driving pressure.

^* At PEEP of 12 cm H₂O in supine position

^† At PEEP of 12 cm H₂O in supine position

Download PDF

Version 1

posted

You are reading this older preprint version

Read the latest preprint version →

Prone Positioning May Increase Lung Overdistension in COVID-19-Induced ARDS

Archived Versions:

Version 1

Abstract

Figures

Background

Methods

Statistical analysis

Results

Discussion

Conclusions

Abbreviations

Declarations

References

Table

Archived Versions:

Version 1