Nebulized Furosemide for Pulmonary Inflammation in Intubated Patients With COVID-19: A Phase 2 Randomized Controlled Double-Blind Study
OBJECTIVES:. Respiratory failure secondary to COVID-19 is associated with morbidity and mortality. Current anti-inflammatory therapies are effective but are given systemically and have significant side effects. Furosemide has anti-inflammatory properties, can be administered by inhalation, and is in...
| Main Authors: | , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Wolters Kluwer
2024-02-01
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| Series: | Critical Care Explorations |
| Online Access: | http://journals.lww.com/10.1097/CCE.0000000000001045 |
| _version_ | 1827307985282531328 |
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| author | John Muscedere, MD David M. Maslove, MD, MS Christopher J. Barden, PhD Donald F. Weaver, MD, PhD J. Gordon Boyd, MD, PhD Stephanie Sibley, MD, MS Tracy Boyd Oleksa Rewa, MD, MSc Martin Albert Marios Roussos, MD, MPH Patrick A. Norman, MSc Andrew G. Day, MSc for the Canadian Critical Care Trials Group |
| author_facet | John Muscedere, MD David M. Maslove, MD, MS Christopher J. Barden, PhD Donald F. Weaver, MD, PhD J. Gordon Boyd, MD, PhD Stephanie Sibley, MD, MS Tracy Boyd Oleksa Rewa, MD, MSc Martin Albert Marios Roussos, MD, MPH Patrick A. Norman, MSc Andrew G. Day, MSc for the Canadian Critical Care Trials Group |
| author_sort | John Muscedere, MD |
| collection | DOAJ |
| description | OBJECTIVES:. Respiratory failure secondary to COVID-19 is associated with morbidity and mortality. Current anti-inflammatory therapies are effective but are given systemically and have significant side effects. Furosemide has anti-inflammatory properties, can be administered by inhalation, and is inexpensive. We investigated the efficacy of nebulized furosemide as an adjunctive therapy for COVID-19 respiratory failure.
DESIGN:. A double-blind, randomized, placebo-controlled trial.
SETTING:. Multicenter ICU study.
PATIENTS:. Adults requiring invasive mechanical ventilation secondary to COVID-19.
INTERVENTION:. Patients were randomized within 48 hours of intubation to receive inhaled furosemide or placebo until day 28, death, or liberation from mechanical ventilation.
MEASUREMENTS AND MAIN RESULTS:. The study was stopped early due to waning incidence of COVID-19; 39 patients were available for analysis with mean ± sd age of 70.5 (10.8) years, Acute Physiology and Chronic Health Evaluation II 26.1 (7.8) and Fio2 60.0% (21.9). Baseline characteristics were similar between the groups. For the primary outcome of change in Pao2/Fio2 ratio between day 1 and day 6, it was +31.4 (83.5) in the furosemide arm versus +20.1 (92.8) in the control (p = 0.58). For secondary outcomes, furosemide versus control: 60-day mortality was 48% versus 71% (p = 0.20), hospital stay was 25.6 (21.9) versus 27.4 (25.0) days, p = 0.94 and VFD was 6.0 (9.1) versus 3.1 (7.1), p value of equals to 0.28. A post hoc analysis of the hierarchical composite outcome, alive and ventilator-free favored furosemide. There were no adverse events.
CONCLUSIONS:. In this trial of inhaled furosemide for COVID-19 respiratory failure, differences in Pao2/Fio2 ratio to day 6 and other clinical outcomes were not significantly different, although the trial was underpowered due to early termination. Given the favorable profile of inhaled furosemide, further study is warranted in disease states where acute pulmonary inflammation contributes to the underlying pathophysiology. |
| first_indexed | 2024-04-24T18:49:36Z |
| format | Article |
| id | doaj.art-75bfeef1c7a44b88adb6c1fa800a9118 |
| institution | Directory Open Access Journal |
| issn | 2639-8028 |
| language | English |
| last_indexed | 2024-04-24T18:49:36Z |
| publishDate | 2024-02-01 |
| publisher | Wolters Kluwer |
| record_format | Article |
| series | Critical Care Explorations |
| spelling | doaj.art-75bfeef1c7a44b88adb6c1fa800a91182024-03-27T03:41:02ZengWolters KluwerCritical Care Explorations2639-80282024-02-0162e104510.1097/CCE.0000000000001045202402000-00003Nebulized Furosemide for Pulmonary Inflammation in Intubated Patients With COVID-19: A Phase 2 Randomized Controlled Double-Blind StudyJohn Muscedere, MD0David M. Maslove, MD, MS1Christopher J. Barden, PhD2Donald F. Weaver, MD, PhD3J. Gordon Boyd, MD, PhD4Stephanie Sibley, MD, MS5Tracy Boyd6Oleksa Rewa, MD, MSc7Martin Albert8Marios Roussos, MD, MPH9Patrick A. Norman, MSc10Andrew G. Day, MSc11for the Canadian Critical Care Trials Group1 Department of Critical Care Medicine, Queen’s University, Kingston, ON, Canada.1 Department of Critical Care Medicine, Queen’s University, Kingston, ON, Canada.4 Krembil Research Institute, University Health Network, Toronto, ON, Canada.4 Krembil Research Institute, University Health Network, Toronto, ON, Canada.1 Department of Critical Care Medicine, Queen’s University, Kingston, ON, Canada.1 Department of Critical Care Medicine, Queen’s University, Kingston, ON, Canada.1 Department of Critical Care Medicine, Queen’s University, Kingston, ON, Canada.6 Department of Critical Care Medicine, University of Alberta, Edmonton, AB, Canada.7 Division of Critical Care, Department of Medicine, Hôpital du Sacré-Coeur Research Center, Université de Montréal, Montreal, QC, Canada.8 Department of Medicine, Division of Critical Care, Hôpital Cité-de-la-Santé, Laval, QC, Canada.2 Kingston Health Sciences Centre, Kingston, ON, Canada.2 Kingston Health Sciences Centre, Kingston, ON, Canada.OBJECTIVES:. Respiratory failure secondary to COVID-19 is associated with morbidity and mortality. Current anti-inflammatory therapies are effective but are given systemically and have significant side effects. Furosemide has anti-inflammatory properties, can be administered by inhalation, and is inexpensive. We investigated the efficacy of nebulized furosemide as an adjunctive therapy for COVID-19 respiratory failure. DESIGN:. A double-blind, randomized, placebo-controlled trial. SETTING:. Multicenter ICU study. PATIENTS:. Adults requiring invasive mechanical ventilation secondary to COVID-19. INTERVENTION:. Patients were randomized within 48 hours of intubation to receive inhaled furosemide or placebo until day 28, death, or liberation from mechanical ventilation. MEASUREMENTS AND MAIN RESULTS:. The study was stopped early due to waning incidence of COVID-19; 39 patients were available for analysis with mean ± sd age of 70.5 (10.8) years, Acute Physiology and Chronic Health Evaluation II 26.1 (7.8) and Fio2 60.0% (21.9). Baseline characteristics were similar between the groups. For the primary outcome of change in Pao2/Fio2 ratio between day 1 and day 6, it was +31.4 (83.5) in the furosemide arm versus +20.1 (92.8) in the control (p = 0.58). For secondary outcomes, furosemide versus control: 60-day mortality was 48% versus 71% (p = 0.20), hospital stay was 25.6 (21.9) versus 27.4 (25.0) days, p = 0.94 and VFD was 6.0 (9.1) versus 3.1 (7.1), p value of equals to 0.28. A post hoc analysis of the hierarchical composite outcome, alive and ventilator-free favored furosemide. There were no adverse events. CONCLUSIONS:. In this trial of inhaled furosemide for COVID-19 respiratory failure, differences in Pao2/Fio2 ratio to day 6 and other clinical outcomes were not significantly different, although the trial was underpowered due to early termination. Given the favorable profile of inhaled furosemide, further study is warranted in disease states where acute pulmonary inflammation contributes to the underlying pathophysiology.http://journals.lww.com/10.1097/CCE.0000000000001045 |
| spellingShingle | John Muscedere, MD David M. Maslove, MD, MS Christopher J. Barden, PhD Donald F. Weaver, MD, PhD J. Gordon Boyd, MD, PhD Stephanie Sibley, MD, MS Tracy Boyd Oleksa Rewa, MD, MSc Martin Albert Marios Roussos, MD, MPH Patrick A. Norman, MSc Andrew G. Day, MSc for the Canadian Critical Care Trials Group Nebulized Furosemide for Pulmonary Inflammation in Intubated Patients With COVID-19: A Phase 2 Randomized Controlled Double-Blind Study Critical Care Explorations |
| title | Nebulized Furosemide for Pulmonary Inflammation in Intubated Patients With COVID-19: A Phase 2 Randomized Controlled Double-Blind Study |
| title_full | Nebulized Furosemide for Pulmonary Inflammation in Intubated Patients With COVID-19: A Phase 2 Randomized Controlled Double-Blind Study |
| title_fullStr | Nebulized Furosemide for Pulmonary Inflammation in Intubated Patients With COVID-19: A Phase 2 Randomized Controlled Double-Blind Study |
| title_full_unstemmed | Nebulized Furosemide for Pulmonary Inflammation in Intubated Patients With COVID-19: A Phase 2 Randomized Controlled Double-Blind Study |
| title_short | Nebulized Furosemide for Pulmonary Inflammation in Intubated Patients With COVID-19: A Phase 2 Randomized Controlled Double-Blind Study |
| title_sort | nebulized furosemide for pulmonary inflammation in intubated patients with covid 19 a phase 2 randomized controlled double blind study |
| url | http://journals.lww.com/10.1097/CCE.0000000000001045 |
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