Ignite Creation Date:
2024-05-06 @ 5:25 PM
Last Modification Date:
2024-10-26 @ 2:28 PM
Study NCT ID:
NCT05304702
Status:
COMPLETED
Last Update Posted:
2022-04-22
First Post:
2022-03-17
Brief Title:
Lung Injury Pulmonary Edema in COVID-19 Treatment With Furosemide and Negative Fluid Balance NEGBAL
Sponsor:
Clinica Colon
Organization:
Clinica Colon
Study Overview
Official Title:
Lung Injury Pulmonary Edema in COVID-19 Treatment With Furosemide and Negative Fluid Balance NEGBAL a Case-Control Study
Status:
COMPLETED
Status Verified Date:
2022-04
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
In COVID-19 pulmonary edema has been attributed to cytokine storm However it is known that SARS-CoV-2 promotes angiotensin-converting enzyme 2 deficiency it increases angiotensin II and this triggers volume overload The current study is based on patients with COVID-19 tomographic evidence of pulmonary edema and volume overload These patients received a standard goal-guided diuretic furosemide treatment Negative Fluid Balance NEGBAL approach This retrospective observational study consists of comparing two groups The cases show patients with COVID-19 and lung injury treated with NEGBAL approach comparing it to the control group consisting of patients with COVID-19 and lung injury receiving standard treatment Medical records of 120 critically ill patients 60 in NEGBAL group and 60 in control group were reviewed demographic clinical laboratory blood gas and chest tomography CT before and during NEGBAL
Once NEGBAL strategy started different aspects were evaluated clinical gasometric and biochemical evolution until the 8th day tomography until the 12th day ICU stay hospital stay and morbidity and mortality until the 30th day
Once NEGBAL strategy started different aspects were evaluated clinical gasometric and biochemical evolution until the 8th day tomography until the 12th day ICU stay hospital stay and morbidity and mortality until the 30th day
Detailed Description:
In December 2019 a new coronavirus known as severe acute respiratory syndrome coronavirus 2 SARS-CoV-2 emerged in Wuhan China and spread throughout the world
In COVID-19 pulmonary edema has been described however the dominant paradigm is focused on cytokine storm as responsible for lung injury and subsequent acute respiratory distress syndrome ARDS Not everyone agreed with this paradigm Sinha et al challenged the role of this cytokine storm given that median interleukin-6 IL-6 levels in non-COVID patients ARDS were up to 200 times higher than in patients with severe COVID-19 Gattinoni et al maintained that COVID-19 presented as an atypical form of ARDS On the other hand Kuba et al and Imai et al reported that angiotensin-converting enzyme 2 ACE2 levels during a SARS-CoV infection are decreased Furthermore in patients with COVID-19 plasma levels of Angiotensin II are higher than in healthy population and stimulate an upregulation of aldosterone level triggering sodium and water retention SARS-CoV-2 enters through ACE2 and downregulates ACE2 expression so that this enzyme is unable to exert its protective effects The dysregulated activity of the renin angiotensin aldosterone system RAAS is partly responsible for pulmonary edema in COVID-19 ACE2 is known for its effect as the main counter-regulatory mechanism for the renin-angiotensin aldosterone system RAAS which is an essential player in blood pressure control by retaining sodium and water and increasing the intravascular fluid volume SARS-CoV-2 binds ACE2 and accelerates the degradation of ACE2 and thus decreases the counteraction of ACE2 on RAAS The final effect is increasing reabsorption of sodium and water and subsequent volume overload The RAAS can be envisioned as a dual function system in which the vasoconstrictorproliferative or vasodilatorantiproliferative actions are primarily driven by the ACE-ACE2 balance According to that an increased ACEACE2 activity ratio generated by the downregulation action of SARS-CoV-2 on ACE2 will lead to increased Angiotensin II and increased catabolism of Angiotensin 1-7 towards vasoconstriction endothelial dysfunction prothrombosis proinflammatory and antinatriuretic effect
Acute pulmonary edema is caused mostly by one of the following mechanisms pulmonary venous pressure elevation-volume overload-or augmentation of the alveolar capillary membrane permeability-inflammation In fact both mechanisms sometimes coexist and the distinction is irrelevant There are bibliographic references of pulmonary edema in COVID-19 as well as evidence of volume overload in COVID-19 Lang et al describes frequent and pronounced vasculature in affected lung areas that may be suggestive of disordered vasoregulation Eslami et al observed increased cardiothoracic ratio and it is also described as right ventricular dilatation In this setting a different approach emerged moderate or severe COVID-19 could experience a severe acute pulmonary edema with a dual hit A first hit of pneumonitis-augmentation of the alveolar capillary membrane permeability-can lead to low hydrostatic pressure pulmonary edema The second hit is high pressure pulmonary edema caused by increase of hydrostatic pressure secondary to volume overload a result of dysregulation of the RAAS This results in a dual hit that triggers severe acute pulmonary edema If this edema is not solved then a third hit appears with secondary inflammation superinfection fibrosis and finally the typical ARDS Consequently the study group looked for patients with pulmonary edema before ARDS was triggered Cases of moderate and severe COVID-19 were searched with tomographic evidence of pulmonary edema dilated superior vena cava large pulmonary arteries diffuse interstitial infiltrates and dilated right ventricle At the detection of pulmonary edema in patients with COVID-19 a standard treatment consisting of oral hydric restriction and diuretics NEGBAL approach was initiated The effects of furosemide on pulmonary edema were well established decades ago To date there is no evidence that had suggested the model of pulmonary edema and volume overload secondary to the dysregulation of the renin angiotensin aldosterone system in COVID-19 The objective of this study is to compare patients with COVID-19 undergoing NEGBAL approach with a control group of patients with COVID-19 of similar demographic clinical gasometric and tomographic characteristics Medical records of 120 adult patients were reviewed demographic clinical laboratory Pro b-type natriuretic peptide pro-BNP negative below 125 pgmL high-sensitivity cardiac troponin hs-cTnT negative 14 ngL blood gas chest tomography CT oxygen therapy support and mechanical ventilation MV requirements all of which were reviewed and recorded by investigators With the purpose of knowing the patients basal hematocrit before COVID-19 prior hematocrit if any defined as hematocrit previous to COVID-19 infection hematocrit prior to admission to NEGBAL was also reviewed
Once the NEGBAL strategy began the clinical tomographic gasometric biochemical evolution was evaluated until the 8th day until the 12th day for tomography ICU stay hospital stay and morbidity and mortality until the 30th day
In COVID-19 pulmonary edema has been described however the dominant paradigm is focused on cytokine storm as responsible for lung injury and subsequent acute respiratory distress syndrome ARDS Not everyone agreed with this paradigm Sinha et al challenged the role of this cytokine storm given that median interleukin-6 IL-6 levels in non-COVID patients ARDS were up to 200 times higher than in patients with severe COVID-19 Gattinoni et al maintained that COVID-19 presented as an atypical form of ARDS On the other hand Kuba et al and Imai et al reported that angiotensin-converting enzyme 2 ACE2 levels during a SARS-CoV infection are decreased Furthermore in patients with COVID-19 plasma levels of Angiotensin II are higher than in healthy population and stimulate an upregulation of aldosterone level triggering sodium and water retention SARS-CoV-2 enters through ACE2 and downregulates ACE2 expression so that this enzyme is unable to exert its protective effects The dysregulated activity of the renin angiotensin aldosterone system RAAS is partly responsible for pulmonary edema in COVID-19 ACE2 is known for its effect as the main counter-regulatory mechanism for the renin-angiotensin aldosterone system RAAS which is an essential player in blood pressure control by retaining sodium and water and increasing the intravascular fluid volume SARS-CoV-2 binds ACE2 and accelerates the degradation of ACE2 and thus decreases the counteraction of ACE2 on RAAS The final effect is increasing reabsorption of sodium and water and subsequent volume overload The RAAS can be envisioned as a dual function system in which the vasoconstrictorproliferative or vasodilatorantiproliferative actions are primarily driven by the ACE-ACE2 balance According to that an increased ACEACE2 activity ratio generated by the downregulation action of SARS-CoV-2 on ACE2 will lead to increased Angiotensin II and increased catabolism of Angiotensin 1-7 towards vasoconstriction endothelial dysfunction prothrombosis proinflammatory and antinatriuretic effect
Acute pulmonary edema is caused mostly by one of the following mechanisms pulmonary venous pressure elevation-volume overload-or augmentation of the alveolar capillary membrane permeability-inflammation In fact both mechanisms sometimes coexist and the distinction is irrelevant There are bibliographic references of pulmonary edema in COVID-19 as well as evidence of volume overload in COVID-19 Lang et al describes frequent and pronounced vasculature in affected lung areas that may be suggestive of disordered vasoregulation Eslami et al observed increased cardiothoracic ratio and it is also described as right ventricular dilatation In this setting a different approach emerged moderate or severe COVID-19 could experience a severe acute pulmonary edema with a dual hit A first hit of pneumonitis-augmentation of the alveolar capillary membrane permeability-can lead to low hydrostatic pressure pulmonary edema The second hit is high pressure pulmonary edema caused by increase of hydrostatic pressure secondary to volume overload a result of dysregulation of the RAAS This results in a dual hit that triggers severe acute pulmonary edema If this edema is not solved then a third hit appears with secondary inflammation superinfection fibrosis and finally the typical ARDS Consequently the study group looked for patients with pulmonary edema before ARDS was triggered Cases of moderate and severe COVID-19 were searched with tomographic evidence of pulmonary edema dilated superior vena cava large pulmonary arteries diffuse interstitial infiltrates and dilated right ventricle At the detection of pulmonary edema in patients with COVID-19 a standard treatment consisting of oral hydric restriction and diuretics NEGBAL approach was initiated The effects of furosemide on pulmonary edema were well established decades ago To date there is no evidence that had suggested the model of pulmonary edema and volume overload secondary to the dysregulation of the renin angiotensin aldosterone system in COVID-19 The objective of this study is to compare patients with COVID-19 undergoing NEGBAL approach with a control group of patients with COVID-19 of similar demographic clinical gasometric and tomographic characteristics Medical records of 120 adult patients were reviewed demographic clinical laboratory Pro b-type natriuretic peptide pro-BNP negative below 125 pgmL high-sensitivity cardiac troponin hs-cTnT negative 14 ngL blood gas chest tomography CT oxygen therapy support and mechanical ventilation MV requirements all of which were reviewed and recorded by investigators With the purpose of knowing the patients basal hematocrit before COVID-19 prior hematocrit if any defined as hematocrit previous to COVID-19 infection hematocrit prior to admission to NEGBAL was also reviewed
Once the NEGBAL strategy began the clinical tomographic gasometric biochemical evolution was evaluated until the 8th day until the 12th day for tomography ICU stay hospital stay and morbidity and mortality until the 30th day
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None