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

Acute Respiratory Distress Syndrome Clinical Trial

Official title:

Inspiratory Ratio: Predictor of Inspiratory Effort Response to High Positive End Expiratory Pressure in Patients Recovering From Acute Respiratory Distress Syndrome.

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04524091
• Other study ID #: 20.2020
• Status: Recruiting
• Start date: August 1, 2020
• Est. completion date: October 1, 2025

Study information

• Verified date: March 2023
• Source: Sanatorio Anchorena San Martin
• Contact: Joaquin Pérez, PT
• Phone: +542245505907
• Email: licjoaquinperez[@]hotmail.com
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

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

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 30
• Est. completion date: October 1, 2025
• Est. primary completion date: March 1, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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).

Related Conditions & MeSH terms

• Acute Lung Injury
• Acute Respiratory Distress Syndrome
• Respiratory Aspiration
• Respiratory Distress Syndrome
• Respiratory Distress Syndrome, Newborn
• Syndrome

Intervention

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.

Locations

Country	Name	City	State
Argentina	Sanatorio Anchorena de San Martin	San Martín	Buenos Aires

Sponsors (1)

Lead Sponsor	Collaborator
Sanatorio Anchorena San Martin

Country where clinical trial is conducted

Argentina, 

References & Publications (10)

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. — View Citation

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, 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. — View Citation

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 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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Inspiratory ratio	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.	10 minutes
Secondary	Esophageal pressure swing	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	10 minutes
Secondary	Dynamic transpulmonary pressure swing	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	10 minutes