Breathing Effort in Covid-19 Pneumonia: Effects of Positive Pressure, Inspired Oxygen Fraction and Decubitus

COVID-19 Pneumonia Clinical Trial

Official title:

Dynamic Transpulmonary Pressure in Covid-19 Pneumonia: Effects of Positive Pressure, Inspired Oxygen Fraction and Decubitus

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04885517
• Other study ID #: 2782
• Status: Recruiting
• Phase: N/A
• Start date: February 1, 2021
• Est. completion date: August 1, 2021

Study information

• Verified date: May 2021
• Source: San Luigi Gonzaga Hospital
• Contact: Pietro Caironi, Pr
• Phone: +390119026386
• Email: pietro.caironi[@]unito.it
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The study investigates the role of positive pressure, inspired oxygen fraction and different decubiti (seated, supine, prone) on breathing effort (as assessed by esophageal pressure swings) in Covid-19 pneumonia (at different disease stages) and in other causes of respiratory failure. The hypothesis is that positive pressure might be deleterious in terms of breathing effort if the main pathological mechanism associated with Sars-CoV-2 infection in the lung is not alveolar damage (as in other causes of respiratory failure) but vascular impairment as previously reported. The effects of high inspired oxygen fractions and decubiti might also be different with respect to other causes of respiratory failure.

Description:

In spite of the overwhelming numbers of the current pandemic, many questions remain open regarding the pathophysiology of Covid-19 associated pneumonia. While some features of the disease (such as the oxygenation improvement associated with proning and/or continuous positive airway pressure) seem to line up with other causes of pneumonia characterized by primary alveolar damage, specific characteristics have been reported about Sars-CoV-2 lung infection which suggest a certain degree of parenchymal preservation and a predominant role of vascular impairment: the dissociation between lung volume and gas exchange, and the so called "happy hypoxemia" both evoke the possibility of mechanisms other than the loss of aeration as causes of hypoxia. Accordingly, evidence are now growing on the role of vascular dysregulation in this regard. It is probable, as previously put forward, that different stages exist in the disease which may account for the discordant findings of previous studies seeking to either associate or separate Covid-19 pneumonia and other causes of respiratory failure. In the present study we will compare the effects of three currently used approaches to improve gas exchange (continuous positive airway pressure, external oxygen administration and decubiti variations) in three different populations (1) early Covid-19 pneumonia, 2) severe late Covid-19 pneumonia and 3) non-Covid-19 pneumonia) in terms of breathing effort as assessed by esophageal pressure swings: our aim is to evaluate, in these populations, the real benefits (beyond the previously reported ones on gas exchange) of such strategies on lung rest. Our hypothesis is that, at least in the early stages of Covid-19 (and as opposed to other causes of respiratory failure), the application of positive pressure might be deleterious if no potential for recruitment, but rather a primary vascular impairment, is associated with hypoxia. If this will be the case the same (or a similar) degree of oxygenation improvement and a safer pattern of ventilation might be attained with the simple administration of oxygen or decubiti variations without the application of positive pressure, thus completely changing the current standards for the treatment of Covid-19 pneumonia.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 72
• Est. completion date: August 1, 2021
• Est. primary completion date: August 1, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

Group 1 (Covid-19 early pneumonia)

• Age > 18

• Positive Sars-CoV 2 nasal swab

• interstitial pneumonia at either CT scan or chest X-ray

• Respiratory failure requiring CPAP for less than 48 hours

• FiO2 =0.5 and CPAP=10 cmH2O

Group 2 (Covid-19 severe pneumonia)

• Age > 18

• Positive Sars-CoV 2 nasal swab

• interstitial pneumonia at either CT scan or chest X-ray

• Respiratory failure requiring CPAP

• Signs of severity with CPAP 10 cmH2O and FiO2 0.5: pulse oximetry (SpO2) = 93% associated to either:

• Dyspnea

• Two or more signs of increased respiratory effort (respiratory rate =25 bpm, use of accessory inspiratory muscles , tirage, intercostal space depression, nasal flaring, expiratory abdominal efforts, PaCO2 < 35)

Group 3 (Non Covid-19 pneumonia)

• Age > 18

• Negative Sars-CoV 2 nasal swab

• CT scan or chest X-ray non compatible with Covid-19 associated pneumonia

• Respiratory failure requiring CPAP

Exclusion Criteria:

Group 1 (Covid-19 early pneumonia)

• Concomitant chronic pulmonary disease

• Chronic heart failure New York Heart Association (NYHA) 3-4

• Bacterial pulmonary associated infection (diagnosed or suspected)

• Pulmonary embolism

• Acute cardiogenic pulmonary edema

• Signs of severity with CPAP 10 cmH2O and FiO2 0.5: SpO2= 93% associated to either:

• Dyspnea

• Two or more signs of increased respiratory effort (respiratory rate =25 bpm, use of accessory inspiratory muscles , tirage, intercostal space depression, nasal flaring, expiratory abdominal efforts, PaCO2 < 35)

• At least one sign of respiratory fatigue/decompensation (pH<7.30 with PaCO2 >45, respiratory rate <15 bpm, paradoxal abdominal breathing, mental status alteration)

Group 2 (Covid-19 severe pneumonia)

• Concomitant chronic pulmonary disease

• Chronic heart failure NYHA 3-4

• Bacterial pulmonary associated infection (diagnosed or suspected)

• Pulmonary embolism

• Acute cardiogenic pulmonary edema

• At least one sign of respiratory fatigue/decompensation (pH<7.30 with PaCO2 >45, respiratory rate <15 bpm, paradoxal abdominal breathing, mental status alteration)

Group 3 (Non Covid-19 pneumonia)

• Concomitant chronic pulmonary disease

• Chronic heart failure NYHA 3-4

• Bacterial pulmonary associated infection (diagnosed or suspected)

• Pulmonary embolism

• Acute cardiogenic pulmonary edema

• At least one sign of respiratory fatigue/decompensation (pH<7.30 with PaCO2 >45, respiratory rate <15 bpm, paradoxal abdominal breathing, mental status alteration)

Related Conditions & MeSH terms

• COVID-19 Pneumonia
• Pneumonia

Intervention

Device:
• Esophageal catheter
Patients are equipped with an esophageal catheter: positioning is performed after accurate nasopharyngeal anesthesia with lidocaine

Locations

Country	Name	City	State
Italy	A.O.U. San Luigi Gonzaga Di Orbassano	Orbassano	Italy/Turin

Sponsors (1)

Lead Sponsor	Collaborator
San Luigi Gonzaga Hospital

Country where clinical trial is conducted

Italy, 

References & Publications (14)

Aliberti S, Radovanovic D, Billi F, Sotgiu G, Costanzo M, Pilocane T, Saderi L, Gramegna A, Rovellini A, Perotto L, Monzani V, Santus P, Blasi F. Helmet CPAP treatment in patients with COVID-19 pneumonia: a multicentre cohort study. Eur Respir J. 2020 Oct — View Citation

Apigo M, Schechtman J, Dhliwayo N, Al Tameemi M, Gazmuri RJ. Development of a work of breathing scale and monitoring need of intubation in COVID-19 pneumonia. Crit Care. 2020 Jul 31;24(1):477. doi: 10.1186/s13054-020-03176-y. — View Citation

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

Chiumello D, Busana M, Coppola S, Romitti F, Formenti P, Bonifazi M, Pozzi T, Palumbo MM, Cressoni M, Herrmann P, Meissner K, Quintel M, Camporota L, Marini JJ, Gattinoni L. Physiological and quantitative CT-scan characterization of COVID-19 and typical A — View Citation

Couzin-Frankel J. The mystery of the pandemic's 'happy hypoxia'. Science. 2020 May 1;368(6490):455-456. doi: 10.1126/science.368.6490.455. — View Citation

Elharrar X, Trigui Y, Dols AM, Touchon F, Martinez S, Prud'homme E, Papazian L. Use of Prone Positioning in Nonintubated Patients With COVID-19 and Hypoxemic Acute Respiratory Failure. JAMA. 2020 Jun 9;323(22):2336-2338. doi: 10.1001/jama.2020.8255. — View Citation

Gattinoni L, Chiumello D, Caironi P, Busana M, Romitti F, Brazzi L, Camporota L. COVID-19 pneumonia: different respiratory treatments for different phenotypes? Intensive Care Med. 2020 Jun;46(6):1099-1102. doi: 10.1007/s00134-020-06033-2. Epub 2020 Apr 14 — View Citation

Gattinoni L, Coppola S, Cressoni M, Busana M, Rossi S, Chiumello D. COVID-19 Does Not Lead to a "Typical" Acute Respiratory Distress Syndrome. Am J Respir Crit Care Med. 2020 May 15;201(10):1299-1300. doi: 10.1164/rccm.202003-0817LE. — View Citation

Gattinoni L, Giosa L, Bonifazi M, Pasticci I, Busana M, Macri M, Romitti F, Vassalli F, Quintel M. Targeting transpulmonary pressure to prevent ventilator-induced lung injury. Expert Rev Respir Med. 2019 Aug;13(8):737-746. doi: 10.1080/17476348.2019.16387 — View Citation

Goligher EC, Jonkman AH, Dianti J, Vaporidi K, Beitler JR, Patel BK, Yoshida T, Jaber S, Dres M, Mauri T, Bellani G, Demoule A, Brochard L, Heunks L. Clinical strategies for implementing lung and diaphragm-protective ventilation: avoiding insufficient and — View Citation

Marini JJ, Gattinoni L. Management of COVID-19 Respiratory Distress. JAMA. 2020 Jun 9;323(22):2329-2330. doi: 10.1001/jama.2020.6825. — View Citation

Poston JT, Patel BK, Davis AM. Management of Critically Ill Adults With COVID-19. JAMA. 2020 May 12;323(18):1839-1841. doi: 10.1001/jama.2020.4914. — View Citation

Tonelli R, Fantini R, Tabbì L, Castaniere I, Pisani L, Pellegrino MR, Della Casa G, D'Amico R, Girardis M, Nava S, Clini EM, Marchioni A. Early Inspiratory Effort Assessment by Esophageal Manometry Predicts Noninvasive Ventilation Outcome in De Novo Respi — View Citation

Vaporidi K, Akoumianaki E, Telias I, Goligher EC, Brochard L, Georgopoulos D. Respiratory Drive in Critically Ill Patients. Pathophysiology and Clinical Implications. Am J Respir Crit Care Med. 2020 Jan 1;201(1):20-32. doi: 10.1164/rccm.201903-0596SO. — View Citation

* Note: There are 14 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Esophageal pressure swings at different levels of positive end-expiratory pressure (PEEP)	The main outcome of the study is represented by the difference in esophageal pressure swings (expiratory minus inspiratory) between the three levels of end expiratory pressure applied (0-7-12 cmH2O)	160 minutes
Secondary	Esophageal pressure swings at different levels of inspired oxygen fraction	One of the secondary outcomes of the study is represented by the difference in esophageal pressure swings (expiratory minus inspiratory) between the two levels of FiO2 applied (0.5-1)	160 minutes
Secondary	Esophageal pressure swings at different decubiti	One of the secondary outcomes of the study is represented by the difference in esophageal pressure swings (expiratory minus inspiratory) between the three decubiti applied (seated, supine, prone)	160 minutes