VILIVORTEX: Ventilator-induced Lung Injury Vortex in Patients With SARS-CoV-2
Study Details
Study Description
Brief Summary
The concept of Ventilator-induced Lung Injury Vortex (VILI vortex) has recently been proposed as a progressive lung injury mechanism in which the alveolar stress/strain increases as the ventilable lung "shrinks" (1). This positive feedback inexorably leads to the acceleration of lung damage, with potentially irreversible results. Little is known about the clinical aspects of this condition. Understanding its behavior could contribute to changing its potential devastating impact.
The objective of this study is to evaluate the incidence of VILI vortex in patients with acute respiratory syndrome (ARDS) secondary to COVID-19, to establish a connection between this phenomenon and mortality, and to identify the factors that have an impact on its development.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Detailed Description
Mechanical ventilation is an essential tool for the treatment of patients with acute respiratory distress syndrome (ARDS). However, as with other strategies, it is not free of complications. Inadequate ventilation may have a negative impact on pulmonary and systemic hemodynamics, and it could both cause structural damage to pulmonary parenchyma and activate inflammation (2). This process is known as ventilator-induced lung injury (VILI) and may promote the development of multiple organ failure and, eventually, death.
VILI results from the interaction between the mechanical load applied to the ventilable lung and its capacity to tolerate it. Factors such as tidal volume (Vt), driving pressure (ΔP), inspiratory flow rate (VI), respiratory rate (RR), excessive inspiratory effort, high levels of FiO2 and, in some cases, PEEP, have been involved in damage mechanism. In that sense, the concept of mechanical power (MP) tries to encompass most of these factors within a measurable unit (3). Furthermore, the decrease in ventilable lung volume (baby lung concept), the heterogeneous lung compromise in ARDS), and the presence of cofactors that have a negative impact on the lung (fluid overload, presence of sepsis or shock) could increase its susceptibility to damage (4-5).
Due to the fact that the mechanical conditions of the lung change dynamically with the progression of the disease, the ventilatory strategy needs constant adjustments in order to maintain a balance between the load and the size of the ventilable lung (concept of ergonomic ventilation). In fact, a protective ventilatory strategy of low tidal volume (Vt: 6 ml/kg/PBW) and limited plateau pressure (PPlat <30 cmH2O) may cause damage if the functional residual capacity (FRC) decreases significantly, thus making a lower number of alveoli (including capillaries) withstand a higher mechanical load per unit.
The concept of VILI vortex has recently been proposed as a progressive lung injury mechanism in which the alveolar stress/strain increases as the ventilable lung "shrinks". This positive feedback inexorably leads to the acceleration of lung damage, with potentially irreversible results (1). Little is known about the clinical aspects of this condition. Understanding its behavior could contribute to changing its potential devastating impact.
The objective of this study is to evaluate the incidence of VILI vortex in patients with ARDS secondary to COVID-19, to establish a connection between this phenomenon and mortality, and to identify the factors that have an impact on its development.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| VILI VORTEX and No VILI VORTEX Measurement of pulmonary pressures and volumes in the same patient |
Diagnostic Test: CT scan
Mechanical variables and PaO2/FiO2 were registered daily for 14 days or until initiating assisted ventilation. These data were obtained in passive mechanical conditions.
Ventilator-induced lung injury vortex was defined as a progressive increase in driving pressure (ΔP) as Vt remained constant or even decreased.
Refractory hypoxemia was defined as PaO2/FiO2 <100 despite the optimization of mechanical ventilation and prone positioning.
Other Names:
|
Outcome Measures
Primary Outcome Measures
- Number of Participants Who Survived and Died [90 days]
The number of patients who died and survived was compared between patients with SARS-CoV-2 who progressed with VILI VORTEX and without VILI VORTEX)
- Number of Patients With and Without Refractory Hypoxemia [90 days]
The number of patients that evolved with refractory hypoxemia was compared between the patients with SARS-CoV-2 that evolved with VILI VORTEX and without VILI VORTEX) Refractory hypoxemia was defined as PaO2/FiO2 <100 despite the optimization of mechanical ventilation and prone positioning.
- Number of Patients With Complications [90 days]
The following variables and complications were also observed during the period of analysis: incidence of pneumonia associated with mechanical ventilation, need for noradrenaline over 0.1 γ/kg/min for more than 24 h, positive blood cultures, accumulated fluid balance, dialysis treatment, clinical and/or echocardiographic evidence of heart failure, lactate ≥2 mmol/L in at least two consecutive samples, presence of persistent fever (≥38º at least once a day for three consecutive days), and the highest value of ferritin, D-dimer, C-reactive protein, troponin I and LDH obtained during the first 14 days of invasive mechanical ventilation. VILI vortex patients had positive blood cultures, moderate to severe shock, persistent fever and fluid balance was considerably more positive.
Eligibility Criteria
Criteria
Inclusion Criteria: ARDS
-
Exclusion Criteria:
Patients with do-not-resuscitate (DNR) orders and pregnant women. Cardiac arrest before ICU admission. Extra corporeal membrane oxygenation (ECMO) requirement within the first 24 h of ICU admission and chronic obstructive pulmonary disease with gold class 3 or 4, or home oxygen therapy
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Nestor Pistillo | Avellaneda | Buenos Aires | Argentina | 1870 |
Sponsors and Collaborators
- Hospital El Cruce
Investigators
- Principal Investigator: Nestor Pistillo, Hospital El Cruce
Study Documents (Full-Text)
More Information
Publications
- Beitler JR, Malhotra A, Thompson BT. Ventilator-induced Lung Injury. Clin Chest Med. 2016 Dec;37(4):633-646. doi: 10.1016/j.ccm.2016.07.004. Epub 2016 Oct 14. Review.
- Gattinoni L, Pesenti A. The concept of "baby lung". Intensive Care Med. 2005 Jun;31(6):776-84. Epub 2005 Apr 6.
- Gattinoni L, Tonetti T, Quintel M. Regional physiology of ARDS. Crit Care. 2017 Dec 28;21(Suppl 3):312. doi: 10.1186/s13054-017-1905-9. Review.
- Marini JJ, Gattinoni L. Time Course of Evolving Ventilator-Induced Lung Injury: The "Shrinking Baby Lung". Crit Care Med. 2020 Aug;48(8):1203-1209. doi: 10.1097/CCM.0000000000004416.
- Vasques F, Duscio E, Cipulli F, Romitti F, Quintel M, Gattinoni L. Determinants and Prevention of Ventilator-Induced Lung Injury. Crit Care Clin. 2018 Jul;34(3):343-356. doi: 10.1016/j.ccc.2018.03.004. Review.
- Nestor Pistillo
Study Results
Participant Flow
| Recruitment Details | Patients were recruited between March 2020 to March 2021 |
|---|---|
| Pre-assignment Detail | No patients with SARS-CoV-2 were excluded from the study prior to group assignment. |
| Arm/Group Title | VILI VORTEX | NO VILI VORTEX |
|---|---|---|
| Arm/Group Description | Clinical categorization of patients with SARS-CoV-2 with VILI vortex | Clinical categorization of patients with SARS-CoV-2 without VILI vortex |
| Period Title: Overall Study | ||
| STARTED | 15 | 50 |
| COMPLETED | 15 | 50 |
| NOT COMPLETED | 0 | 0 |
Baseline Characteristics
| Arm/Group Title | VILI VORTEX | No VILI VORTEX | Total |
|---|---|---|---|
| Arm/Group Description | Participants who evolved with VILI vortex clinical criteria | Participants who evolved without clinical criteria for VILI vortex | Total of all reporting groups |
| Overall Participants | 15 | 50 | 65 |
| Age (years) [Median (Inter-Quartile Range) ] | |||
| Median (Inter-Quartile Range) [years] |
59
|
60
|
60
|
| Sex: Female, Male (Count of Participants) | |||
| Female |
6
40%
|
18
36%
|
24
36.9%
|
| Male |
9
60%
|
32
64%
|
41
63.1%
|
| Race (NIH/OMB) (Count of Participants) | |||
| American Indian or Alaska Native |
0
0%
|
0
0%
|
0
0%
|
| Asian |
0
0%
|
0
0%
|
0
0%
|
| Native Hawaiian or Other Pacific Islander |
0
0%
|
0
0%
|
0
0%
|
| Black or African American |
0
0%
|
0
0%
|
0
0%
|
| White |
15
100%
|
50
100%
|
65
100%
|
| More than one race |
0
0%
|
0
0%
|
0
0%
|
| Unknown or Not Reported |
0
0%
|
0
0%
|
0
0%
|
| Region of Enrollment (participants) [Number] | |||
| Argentina |
15
100%
|
50
100%
|
65
100%
|
| Comorbidities (participants) [Number] | |||
| Hypertension |
9
60%
|
25
50%
|
34
52.3%
|
| Diabetes Mellitus |
25
166.7%
|
33
66%
|
58
89.2%
|
| Obesity |
5
33.3%
|
11
22%
|
16
24.6%
|
| Ischemic heart disease |
2
13.3%
|
6
12%
|
8
12.3%
|
| COPD |
3
20%
|
7
14%
|
10
15.4%
|
| Cancer/immunosupresion |
4
26.7%
|
6
12%
|
10
15.4%
|
Outcome Measures
| Title | Number of Participants Who Survived and Died |
|---|---|
| Description | The number of patients who died and survived was compared between patients with SARS-CoV-2 who progressed with VILI VORTEX and without VILI VORTEX) |
| Time Frame | 90 days |
Outcome Measure Data
| Analysis Population Description |
|---|
| The evolution of the patients was compared with Chi square, significant p <0.05 |
| Arm/Group Title | VILI VORTEX | No VILI VORTEX |
|---|---|---|
| Arm/Group Description | Patients who evolved with clinical criteria of VILI VORTEX | Patients who evolved without clinical criteria of VILI VORTEX |
| Measure Participants | 15 | 50 |
| Survivors |
1
6.7%
|
31
62%
|
| Dead |
14
93.3%
|
19
38%
|
| Title | Number of Patients With and Without Refractory Hypoxemia |
|---|---|
| Description | The number of patients that evolved with refractory hypoxemia was compared between the patients with SARS-CoV-2 that evolved with VILI VORTEX and without VILI VORTEX) Refractory hypoxemia was defined as PaO2/FiO2 <100 despite the optimization of mechanical ventilation and prone positioning. |
| Time Frame | 90 days |
Outcome Measure Data
| Analysis Population Description |
|---|
| The baseline characteristics of the population were similar for both groups. |
| Arm/Group Title | No VILI VORTEX | VILI VORTEX |
|---|---|---|
| Arm/Group Description | Participants who evolved without clinical criteria for VILI vortex | Participants who evolved with VILI vortex clinical criteria |
| Measure Participants | 50 | 15 |
| with refractory hypoxemia |
1
6.7%
|
14
28%
|
| no refractory hypoxemia |
49
326.7%
|
1
2%
|
| Title | Number of Patients With Complications |
|---|---|
| Description | The following variables and complications were also observed during the period of analysis: incidence of pneumonia associated with mechanical ventilation, need for noradrenaline over 0.1 γ/kg/min for more than 24 h, positive blood cultures, accumulated fluid balance, dialysis treatment, clinical and/or echocardiographic evidence of heart failure, lactate ≥2 mmol/L in at least two consecutive samples, presence of persistent fever (≥38º at least once a day for three consecutive days), and the highest value of ferritin, D-dimer, C-reactive protein, troponin I and LDH obtained during the first 14 days of invasive mechanical ventilation. VILI vortex patients had positive blood cultures, moderate to severe shock, persistent fever and fluid balance was considerably more positive. |
| Time Frame | 90 days |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | VILI VORTEX | No VILI VORTEX |
|---|---|---|
| Arm/Group Description | Participants who evolved with VILI vortex clinical criteria | Participants who evolved without clinical criteria for VILI vortex |
| Measure Participants | 15 | 50 |
| intranosocomial pneumonia |
7
46.7%
|
19
38%
|
| Renal replacement therapy |
7
46.7%
|
18
36%
|
| Persistent fever |
7
46.7%
|
10
20%
|
| Bood cultures |
9
60%
|
10
20%
|
Adverse Events
| Time Frame | up to 12 weeks after entering the study | |||
|---|---|---|---|---|
| Adverse Event Reporting Description | Refractory hypoxemia was defined as PaO2/FiO2 <100 despite the optimization of mechanical ventilation and prone positioning. | |||
| Arm/Group Title | VILI VORTEX | NO VILI VORTEX | ||
| Arm/Group Description | SARS-CoV-2 patients who evolved with VILI VORTEX | SARS-CoV-2 patients who evolved without VILI VORTEX | ||
All Cause Mortality |
||||
| VILI VORTEX | NO VILI VORTEX | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 14/15 (93.3%) | 19/50 (38%) | ||
Serious Adverse Events |
||||
| VILI VORTEX | NO VILI VORTEX | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 14/15 (93.3%) | 23/50 (46%) | ||
| Infections and infestations | ||||
| Intranosocomial pneumonia | 7/15 (46.7%) | 7 | 19/50 (38%) | 19 |
| Blood cultures | 9/15 (60%) | 9 | 10/50 (20%) | 10 |
| Renal and urinary disorders | ||||
| Severe Kidney Failure | 7/15 (46.7%) | 7 | 18/50 (36%) | 18 |
| Respiratory, thoracic and mediastinal disorders | ||||
| Refractory hipoxemy | 14/15 (93.3%) | 14 | 1/50 (2%) | 1 |
Other (Not Including Serious) Adverse Events |
||||
| VILI VORTEX | NO VILI VORTEX | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 10/15 (66.7%) | 20/50 (40%) | ||
| General disorders | ||||
| Persistent fever | 7/15 (46.7%) | 7 | 10/50 (20%) | 10 |
| Vascular disorders | ||||
| Lactate level >2mmol/L | 7/15 (46.7%) | 7 | 16/50 (32%) | 16 |
Limitations/Caveats
More Information
Certain Agreements
All Principal Investigators ARE employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
| Name/Title | Nestor Pistillo |
|---|---|
| Organization | Hospital El Cruce |
| Phone | 054 1142109000 ext 5636 |
| npistillo@yahoo.com.ar |
- Nestor Pistillo