Ventilatory Efficiency in Critically Ill COVID-19 Patients

The new severe acute respiratory syndrome coronavirus 2019 (SARS-CoV-2) causes the illness named COVID-19, which is primarily characterized by pneumonia. As of 27 December, there have been over 79.2 million cases and over 1.7 million deaths reported since the start of the pandemic. In many cases, pneumonia evolves to acute respiratory distress syndrome (ARDS) with the need for mechanical ventilation and patient admission to intensive care unit, determining a marked increase in the need for intensive care beds worldwide.

Pulmonary involvement causes predominantly hypoxemic respiratory failure. Although COVID-19 pneumonia often falls within the diagnostic criteria of ARDS, it differs from it for some peculiar pathophysiological characteristics. In particular, patients with ARDS secondary to COVID-19 often have the compliance of the respiratory system within the normal range. A significant role in the pathophysiology of hypoxemia seems to depend on vascular alterations such as altered pulmonary vascular self-regulation, pulmonary capillary leakage, and microvascular thrombosis in a complex process known as "immunothrombosis". All together they act by altering the relationship between ventilation and perfusion and increasing the dead space, which ultimately results in impaired efficiency of the pulmonary ventilation. Among the various markers associated with the prognosis of patients with COVID-19, D-dimer is linked to both the inflammatory state and thrombotic phenomena and could help to identify patients at greater risk of developing early ventilation-perfusion changes.

This study aims at measuring the ventilatory efficiency, assessed by Ventilatory Ratio, in critically ill, mechanically ventilated, COVID-19 patients and its correlation with plasma D-dimer and quasi-static respiratory compliance.

Study Overview

• Status: Unknown
• Conditions: ARDS
• Intervention / Treatment: Other: data collecting

• Study Type: Observational
• Enrollment (Anticipated): 100

Contacts and Locations

• Study Contact: Name: Riccardo Colombo, M.D.; Phone Number: +390239043023; Email: riccardo.colombo@asst-fbf-sacco.it
• Study Contact Backup: Name: Andrea Agarossi, M.D.

Study Locations

• Italy
  • Emilia Romagna
    • Ferrara, Emilia Romagna, Italy, 44124
      • Not yet recruiting
      • Arcispedale Sant'Anna
      • Contact: Alberto Fogagnolo, M.D.; Email: alberto.fogagnolo@gmail.com
      • Principal Investigator: Alberto Fogagnolo, M.D.
    • Rimini, Emilia Romagna, Italy, 47923
      • Not yet recruiting
      • Ospedale Infermi
      • Contact: Jonathan Montomoli, M.D.; Email: jonathan.montomoli@gmail.com
      • Principal Investigator: Jonathan Montomoli, M.D.
  • Lombardy
    • Milan, Lombardy, Italy, 20157
      • Recruiting
      • ASST Fatebenefratelli Sacco
      • Contact: Riccardo Colombo, M.D.; Phone Number: 0239043023; Email: riccardo.colombo@asst-fbf-sacco.it
      • Sub-Investigator: Riccardo Colombo, M.D.
      • Principal Investigator: Andrea Agarossi, M.D.
  • Marche
    • Ancona, Marche, Italy, 60126
      • Recruiting
      • Azienda Ospedaliero Universitaria Ospedali Riuniti
      • Contact: Andrea Carsetti, M.D.; Email: a.carsetti@staff.univpm.it
      • Principal Investigator: Andrea Carsetti, M.D.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 90 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

All patients consecutively admitted to ICU with the eligibility criteria will be enrolled in the study. They will be treated according to the standard of care.

Description

Inclusion Criteria:

All of the following:

• confirmed SARS-CoV-2 infection by RT-PCR on a nasopharyngeal swab
• severe hypoxemia due to COVID-19 who meets the diagnostic criteria of ARDS (Berlin's definition)
• invasive mechanical ventilation
• patients receiving neuromuscular blocking drugs

Exclusion Criteria:

• history of preexisting severe hypoxemia (i.e. primary pulmonary hypertension, COPD in therapy with O2 supplementation, pulmonary fibrosis, etc.)

• severe haemodynamic instability defined as:

  • Mean arterial pressure < 65 mmHg despite the infusion of norepinephrine, or epinephrine, or dobutamine, or levosimendan
  • severe left ventricular dysfunction with ejection fraction <20%
  • right ventricular failure due to pulmonary embolism

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort

Intervention / Treatment

ARDS COVID-19; Patients who meet Berlin's ARDS diagnostic criteria, with confirmed SARS-CoV-2 infection, requiring invasive mechanical ventilation.

Other: data collecting; Within 24h from ICU admission, the ventilatory efficiency will be assessed by the following Ventilatory Ratio equation: Ventilatory Ratio = [minute ventilation (ml/min) × PaCO2 (mm Hg)]/(predicted body weight × 100 × 37.5). Where PaCO2 is the partial pressure of carbon dioxide in mmHg in the arterial blood. Tha quasi-static compliance will be calculated according to the equation: C=Tidal Volume/(Paw plateau - PEEP total) where Paw plateau is the airway pressure measured during 4 seconds of inspiratory pause, PEEP total is the airway pressure measured during 4 seconds of expiratory pause. In the same time frame, complete blood count, d-dimer, sequential organ failure assessment score, blood gas analysis, haemodynamic and ventilatory parameters will be collected.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Ventilatory ratio correlation	Measure the correlation between ventilatory ratio, plasma D-dimer, and quasi-static compliance of the respiratory system	24 hours from ICU admission

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mortality	Mortality among subgroups stratified according to Ventilatory ratio and quasi-static respiratory compliance. Subgroup will be identified according centiles of the distribution values of 1) Ventilatory Ratio, and 2) quasi-static compliance both measured in the first 24 hours.	30 days

Collaborators and Investigators

• Sponsor: ASST Fatebenefratelli Sacco
• Collaborators: S. Anna Hospital; Azienda Ospedaliero, Universitaria Ospedali Riuniti; Ospedale Infermi Rimini
• Investigators: Principal Investigator: Riccardo Colombo, M.D., ASST Fatebenefratelli Sacco - Ospedale Luigi Sacco

Publications and helpful links

General Publications

• Sinha P, Calfee CS, Beitler JR, Soni N, Ho K, Matthay MA, Kallet RH. Physiologic Analysis and Clinical Performance of the Ventilatory Ratio in Acute Respiratory Distress Syndrome. Am J Respir Crit Care Med. 2019 Feb 1;199(3):333-341. doi: 10.1164/rccm.201804-0692OC.
• ARDS Definition Task Force; 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 Jun 20;307(23):2526-33. doi: 10.1001/jama.2012.5669.
• WHO Weekly epidemiological update - 29 December 2020 - https://www.who.int/publications/m/item/weekly-epidemiological-update---29-december-2020

Study record dates

Study Major Dates

• Study Start (Actual): September 1, 2020
• Primary Completion (Anticipated): March 31, 2021
• Study Completion (Anticipated): April 15, 2021

Study Registration Dates

• First Submitted: January 3, 2021
• First Submitted That Met QC Criteria: January 3, 2021
• First Posted (Actual): January 5, 2021

Study Record Updates

• Last Update Posted (Actual): January 5, 2021
• Last Update Submitted That Met QC Criteria: January 3, 2021
• Last Verified: January 1, 2021

More Information

Terms related to this study

• Keywords: COVID-19; ARDS; Critical illness; Mechanical ventilation; Ventilatory ratio; Dead-space
• Additional Relevant MeSH Terms: Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Pneumonia, Viral; Pneumonia; Lung Diseases; COVID-19
• Other Study ID Numbers: VentRatio-19

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No