Prediction of Inspiratory Effort Response to High PEEP in Patients Recovering From ARDS

Overview

Spontaneous breathing during the transition from controlled to assisted ventilation in ARDS may be harmful, as high respiratory drive can generate large transpulmonary pressure swings and worsen lung injury. Higher PEEP may mitigate this by reducing inspiratory effort and lung stress, but patient response is variable and difficult to predict. While improved lung compliance appears to mediate the protective effects of PEEP, its bedside assessment is complex. Preclinical data suggest that changes in compliance are inversely reflected by changes in respiratory rate, but this relationship and its clinical utility in ARDS patients remain unclear.

Detailed description

Spontaneous Breathing (SB) can be potentially harmful in patient with Acute Respiratory Distress Syndrome (ARDS) during the transition phase of passive ventilation to partial ventilatory support. A high respiratory drive and consequently, a strong inspiratory effort, may produce large transpulmonary pressure (TP) swings mainly in dependent lung regions closer to the diaphragm and cause alveolar rupture and inflammatory mediators release.

The application of high Positive End Expiratory Pressure (PEEP) during SB has shown to ameliorate the progression of lung injury by decreasing the TP and esophageal pressure (EP) swings and the stress / strain applied to the lung. However, it is uncertain which patient will respond adequately to the application of high PEEP and consequently will reduce the inspiratory effort.

Recent evidence suggests that high PEEP may confer protective effects when lung compliance improves. However, assessing lung compliance at the bedside is challenging, as it requires esophageal pressure monitoring. Simpler tools to identify lung compliance response to PEEP are neccesary.

Preclinical data suggest that the changes in compliance are followed by opposite changes in respiratory rate (RR) - i.e., if compliance improves, RR decreases and vicerversa. However, if this behaviour is also observed in ARDS patients ventilated at different PEEP levels is unkown. Additionally, whether changes in RR can be useful to identify changes in lung compliance when increasing PEEP has never been tested.

Interventions

• Other Positive end expiratory pressure
  Initially, the patients will be ventilated using pressure support ventilation with an inspiratory pressure adjusted to achieve 6 - 8 ml/kg of PBW with a minimal esophageal pressure swing of 5 cmH2O and a PEEP of 5 cmH2O. After 5 minutes, we will collect basic and advanced respiratory monitoring, including esophageal pressure and transpulmonary pressure swings. The same procedure will be carried out with 10 and 15 cmH2O of PEEP. Inspiratory pressure will be kept constant throughout the protocol.

Primary outcome measures

• Lung compliance response [Time frame: 10 minutes]

Secondary outcome measures (3)

• Esophageal pressure swing [Time frame: 10 minutes]
• Dynamic transpulmonary pressure swing [Time frame: 10 minutes]
• Respiratory rate response [Time frame: 10 minutes]

Eligibility criteria

Inclusion criteria

• Need of invasive mechanical ventilation
• Patients who had fulfill ARDS criteria based on Berlin definition during any time of invasive mechanical ventilation.
• Patient ventilated in pressure support ventilation.
• Time of invasive ventilation expected to be longer than 24 hs after the day of enrollment.

Exclusion criteria

• Neuromuscular diseases (e.g., amyotrophic lateral sclerosis, Duchenne Erb)
• previous diagnosis of chronic obstructed pulmonary disease
• not resolved pneumothorax
• bronchopleural fistula
• suspicion of central respiratory drive alteration (e.g., benzodiazepines intoxication).

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Observational model

Cohort

Study locations

Argentina · 1 center

• Sanatorio Anchorena de San Martin — San Martín

Publications

• Esteban A, Frutos-Vivar F, Muriel A, Ferguson ND, Penuelas O, Abraira V, Raymondos K, Rios F, Nin N, Apezteguia C, Violi DA, Thille AW, Brochard L, Gonzalez M, Villagomez AJ, Hurtado J, Davies AR, Du B, Maggiore SM, Pelosi P, Soto L, Tomicic V, D'Empaire G, Matamis D, Abroug F, Moreno RP, Soares MA, Arabi Y, Sandi F, Jibaja M, Amin P, Koh Y, Kuiper MA, Bulow HH, Zeggwagh AA, Anzueto A. Evolution o PMID 23631814
• DAS-Taskforce 2015; Baron R, Binder A, Biniek R, Braune S, Buerkle H, Dall P, Demirakca S, Eckardt R, Eggers V, Eichler I, Fietze I, Freys S, Frund A, Garten L, Gohrbandt B, Harth I, Hartl W, Heppner HJ, Horter J, Huth R, Janssens U, Jungk C, Kaeuper KM, Kessler P, Kleinschmidt S, Kochanek M, Kumpf M, Meiser A, Mueller A, Orth M, Putensen C, Roth B, Schaefer M, Schaefers R, Schellongowski P, Schin PMID 26609286
• Schepens T, Dres M, Heunks L, Goligher EC. Diaphragm-protective mechanical ventilation. Curr Opin Crit Care. 2019 Feb;25(1):77-85. doi: 10.1097/MCC.0000000000000578. PMID 30531536
• Mauri T, Cambiaghi B, Spinelli E, Langer T, Grasselli G. Spontaneous breathing: a double-edged sword to handle with care. Ann Transl Med. 2017 Jul;5(14):292. doi: 10.21037/atm.2017.06.55. PMID 28828367
• Goligher EC, Fan E, Herridge MS, Murray A, Vorona S, Brace D, Rittayamai N, Lanys A, Tomlinson G, Singh JM, Bolz SS, Rubenfeld GD, Kavanagh BP, Brochard LJ, Ferguson ND. Evolution of Diaphragm Thickness during Mechanical Ventilation. Impact of Inspiratory Effort. Am J Respir Crit Care Med. 2015 Nov 1;192(9):1080-8. doi: 10.1164/rccm.201503-0620OC. PMID 26167730
• Telias I, Brochard L, Goligher EC. Is my patient's respiratory drive (too) high? Intensive Care Med. 2018 Nov;44(11):1936-1939. doi: 10.1007/s00134-018-5091-2. Epub 2018 Mar 1. No abstract available. PMID 29497778
• Brochard L, Slutsky A, Pesenti A. Mechanical Ventilation to Minimize Progression of Lung Injury in Acute Respiratory Failure. Am J Respir Crit Care Med. 2017 Feb 15;195(4):438-442. doi: 10.1164/rccm.201605-1081CP. PMID 27626833
• Morais CCA, Koyama Y, Yoshida T, Plens GM, Gomes S, Lima CAS, Ramos OPS, Pereira SM, Kawaguchi N, Yamamoto H, Uchiyama A, Borges JB, Vidal Melo MF, Tucci MR, Amato MBP, Kavanagh BP, Costa ELV, Fujino Y. High Positive End-Expiratory Pressure Renders Spontaneous Effort Noninjurious. Am J Respir Crit Care Med. 2018 May 15;197(10):1285-1296. doi: 10.1164/rccm.201706-1244OC. PMID 29323536

Identifiers

NCT: NCT04524091 · 20.2020

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗