Inspiratory Ratio: Predictor of Inspiratory Effort Response to High PEEP in Patients Recovering From ARDS

• ClinicalTrials.gov Identifier: NCT04524091
• Recruitment Status: Completed
• First Posted: August 24, 2020
• Last Update Posted: August 31, 2021
• Sponsor: Sanatorio Anchorena San Martin
• Information provided by (Responsible Party): Matias Accoce, Sanatorio Anchorena San Martin

Study Description

Brief Summary:

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. 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. The mechanisms proposed to be responsible for these effects are the activation of Hering Breuer reflex, the recruitment of previously collapsed tissue, the homogenization of lung and the improvement of respiratory system compliance and the impairment in the length - tension relationship of the diaphragm. If all the previously explained mechanisms have an effect on the control of inspiratory effort, a decrease in the intensity of effort is expected during an end-inspiratory occlusion in patients who will respond to high PEEP application. Based on this rationale, the investigators developed an index called "Inspiratory Ratio" (IR) to predict the response of patient's inspiratory effort to the application of high PEEP without need of esophageal manometry.

Condition or disease	Intervention/treatment
Acute Respiratory Distress Syndrome	Other: Positive end expiratory pressure

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. The mechanisms proposed to be responsible for these effects are the activation of Hering Breuer reflex caused by a greater stretch of the lung parenchyma at the end of inspiration; the recruitment of previously collapsed tissue, the homogenization of lung ("fluid like behavior") and the improvement of respiratory system compliance (Crs); and the impairment in the length - tension relationship of the diaphragm which produces mechanical disadvantage to generate force due to a higher lung volume. However, it is uncertain which patient will respond adequately to the application of high PEEP and consequently will reduce the inspiratory effort.

If all the previously explained mechanisms have an effect on the control of inspiratory effort, in patients who will respond to high PEEP application, a decrease in inspiratory effort is expected during an end-inspiratory occlusion. At end-inspiration lung parenchyma is more homogeneous, the lung volume is higher and the diaphragmic dome is flatter compared to the physiological condition end of expiration, where the lung volume is lower, the parenchyma is more heterogeneous and the diaphragmatic neuromechanical coupling is better. Based on this rationale, the investigators developed an index called "Inspiratory Ratio" (IR) to predict the response of patient's inspiratory effort to the application of high PEEP without having to measure esophageal pressure.

The IR will be calculated using the following formula: (IPSexp - IPSinsp ) / (IPSexp) x 100

IPSexp = negative deflection in airway pressure expiratory pause; IPSinsp = negative deflection in airway pressure end inspiratory pause

Study Design

• Study Type: Observational
• Actual Enrollment: 15 participants
• Observational Model: Cohort
• Time Perspective: Prospective
• Official Title: Inspiratory Ratio: Predictor of Inspiratory Effort Response to High Positive End Expiratory Pressure in Patients Recovering From Acute Respiratory Distress Syndrome.
• Actual Study Start Date: August 1, 2020
• Actual Primary Completion Date: April 1, 2021
• Actual Study Completion Date: April 1, 2021

Groups and Cohorts

Intervention Details:

• 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 measure five IPSexp and five IPSinsp in random order and considering a resting period between each occlusion in order to avoid learning effect and disconfort. The IR will be calculated using the average of the measured IPSexp and the average of the IPSinsp. Besides, we will register the average of esophageal pressure and transpulmonary pressure swings continuously. The same procedure will be carried out with 10 and 15 cmH2O of PEEP. Inspiratory pressure will be kept constant throughout the protocol.

Outcome Measures

Primary Outcome Measures :

1. Inspiratory ratio [ Time Frame: 10 minutes ]
   Inspiratory ratio will be calculated using the formula (IPSexp - IPSinsp )/IPSexp x 100, being IPSexp = negative deflection in airway pressure during an end expiratory pause; IPSinsp = negative deflection in airway pressure during an end inspiratory pause.

Secondary Outcome Measures :

1. Esophageal pressure swing [ Time Frame: 10 minutes ]
   Esophageal pressure swing will be calculated as the difference between end expiration and end inspiration esophageal pressure during the las 30-60 seconds of each PEEP condition evaluated
2. Dynamic transpulmonary pressure swing [ Time Frame: 10 minutes ]
   Dynamic transpulmonary pressure swing will be calculated as the difference between end expiration and end inspiration dynamic transpulmonary pressure during the las 30-60 seconds of each PEEP condition evaluated

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No
• Sampling Method: Non-Probability Sample

Study Population

Patients with acute respiratory distress syndrome ventilated using an endotracheal tube admitted to Anchorena San Martin intensive care unit who are ventilated in pressure support ventilation.

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).

Contacts and Locations

Locations

Argentina

Sanatorio Anchorena de San Martin

San Martín, Buenos Aires, Argentina, B1650CQU

Sponsors and Collaborators

Sanatorio Anchorena San Martin

More Information

Publications:

Esteban A, Frutos-Vivar F, Muriel A, Ferguson ND, Peñuelas O, Abraira V, Raymondos K, Rios F, Nin N, Apezteguía C, Violi DA, Thille AW, Brochard L, González 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, Bülow HH, Zeggwagh AA, Anzueto A. Evolution of mortality over time in patients receiving mechanical ventilation. Am J Respir Crit Care Med. 2013 Jul 15;188(2):220-30. doi: 10.1164/rccm.201212-2169OC.

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, Fründ 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, Schindler M, Schmitt R, Scholz J, Schroeder S, Schwarzmann G, Spies C, Stingele R, Tonner P, Trieschmann U, Tryba M, Wappler F, Waydhas C, Weiss B, Weisshaar G. Evidence and consensus based guideline for the management of delirium, analgesia, and sedation in intensive care medicine. Revision 2015 (DAS-Guideline 2015) - short version. Ger Med Sci. 2015 Nov 12;13:Doc19. doi: 10.3205/000223. eCollection 2015. Review.

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. Review.

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. Review.

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.

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.

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.

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.

Yoshida T, Uchiyama A, Matsuura N, Mashimo T, Fujino Y. Spontaneous breathing during lung-protective ventilation in an experimental acute lung injury model: high transpulmonary pressure associated with strong spontaneous breathing effort may worsen lung injury. Crit Care Med. 2012 May;40(5):1578-85. doi: 10.1097/CCM.0b013e3182451c40.

Mauri T, Bellani G, Confalonieri A, Tagliabue P, Turella M, Coppadoro A, Citerio G, Patroniti N, Pesenti A. Topographic distribution of tidal ventilation in acute respiratory distress syndrome: effects of positive end-expiratory pressure and pressure support. Crit Care Med. 2013 Jul;41(7):1664-73. doi: 10.1097/CCM.0b013e318287f6e7.

• Responsible Party: Matias Accoce, Head of physica therapy department, Sanatorio Anchorena San Martin
• ClinicalTrials.gov Identifier: NCT04524091
• Other Study ID Numbers: 20.2020
• First Posted: August 24, 2020
• Last Update Posted: August 31, 2021
• Last Verified: August 2021

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Undecided

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Respiratory Distress Syndrome; Respiratory Distress Syndrome, Newborn; Acute Lung Injury; Respiratory Aspiration; Syndrome; Disease; Pathologic Processes; Lung Diseases; Respiratory Tract Diseases; Respiration Disorders; Infant, Premature, Diseases; Infant, Newborn, Diseases; Lung Injury