tetano
Editor, Senior Moderator
Front Med (Lausanne)
. 2022 Jan 4;8:797647.
doi: 10.3389/fmed.2021.797647. eCollection 2021.
The Association of an Alpha-2 Adrenergic Receptor Agonist and Mortality in Patients With COVID-19
John L Hamilton[SUP] 1 [/SUP], Mona Vashi[SUP] 2 [/SUP], Ekta B Kishen[SUP] 3 [/SUP], Louis F Fogg[SUP] 4 [/SUP], Markus A Wimmer[SUP] 1 [/SUP], Robert A Balk[SUP] 2 [/SUP]
Affiliations
Abstract
There is a need for treatments to reduce coronavirus disease 2019 (COVID-19) mortality. Alpha-2 adrenergic receptor (α[SUB]2[/SUB] AR) agonists can dampen immune cell and inflammatory responses as well as improve oxygenation through physiologic respiratory parameters. Therefore, α[SUB]2[/SUB] AR agonists may be effective in reducing mortality related to hyperinflammation and acute respiratory failure in COVID-19. Dexmedetomidine (DEX) is an α[SUB]2[/SUB] AR agonist used for sedation. We performed a retrospective analysis of adults at Rush University System for Health hospitals between March 1, 2020 and July 30, 2020 with COVID-19 requiring invasive mechanical ventilation and sedation (n = 214). We evaluated the association of DEX use and 28-day mortality from time of intubation. Overall, 28-day mortality in the cohort receiving DEX was 27.0% as compared to 64.5% in the cohort that did not receive DEX (relative risk reduction 58.2%; 95% CI 42.4-69.6). Use of DEX was associated with reduced 28-day mortality on multivariable Cox regression analysis (aHR 0.19; 95% CI 0.10-0.33; p < 0.001). Adjusting for time-varying exposure to DEX also demonstrated that DEX was associated with reduced 28-day mortality (aHR 0.51; 95% CI 0.28-0.95; p = 0.03). Earlier DEX use, initiated <3.4 days from intubation, was associated with reduced 28-day mortality (aHR 0.25; 95% CI 0.13-0.50; p < 0.001) while later DEX use was not (aHR 0.64; 95% CI 0.27-1.50; p = 0.30). These results suggest an α[SUB]2[/SUB] AR agonist might reduce mortality in patients with COVID-19. Randomized controlled trials are needed to confirm this observation.
Keywords: alpha-2 adrenergic receptor agonist; coronavirus disease 2019 (COVID-19); dexmedetomidine; mortality; severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).
. 2022 Jan 4;8:797647.
doi: 10.3389/fmed.2021.797647. eCollection 2021.
The Association of an Alpha-2 Adrenergic Receptor Agonist and Mortality in Patients With COVID-19
John L Hamilton[SUP] 1 [/SUP], Mona Vashi[SUP] 2 [/SUP], Ekta B Kishen[SUP] 3 [/SUP], Louis F Fogg[SUP] 4 [/SUP], Markus A Wimmer[SUP] 1 [/SUP], Robert A Balk[SUP] 2 [/SUP]
Affiliations
- PMID: 35059419
- PMCID: PMC8764306
- DOI: 10.3389/fmed.2021.797647
Abstract
There is a need for treatments to reduce coronavirus disease 2019 (COVID-19) mortality. Alpha-2 adrenergic receptor (α[SUB]2[/SUB] AR) agonists can dampen immune cell and inflammatory responses as well as improve oxygenation through physiologic respiratory parameters. Therefore, α[SUB]2[/SUB] AR agonists may be effective in reducing mortality related to hyperinflammation and acute respiratory failure in COVID-19. Dexmedetomidine (DEX) is an α[SUB]2[/SUB] AR agonist used for sedation. We performed a retrospective analysis of adults at Rush University System for Health hospitals between March 1, 2020 and July 30, 2020 with COVID-19 requiring invasive mechanical ventilation and sedation (n = 214). We evaluated the association of DEX use and 28-day mortality from time of intubation. Overall, 28-day mortality in the cohort receiving DEX was 27.0% as compared to 64.5% in the cohort that did not receive DEX (relative risk reduction 58.2%; 95% CI 42.4-69.6). Use of DEX was associated with reduced 28-day mortality on multivariable Cox regression analysis (aHR 0.19; 95% CI 0.10-0.33; p < 0.001). Adjusting for time-varying exposure to DEX also demonstrated that DEX was associated with reduced 28-day mortality (aHR 0.51; 95% CI 0.28-0.95; p = 0.03). Earlier DEX use, initiated <3.4 days from intubation, was associated with reduced 28-day mortality (aHR 0.25; 95% CI 0.13-0.50; p < 0.001) while later DEX use was not (aHR 0.64; 95% CI 0.27-1.50; p = 0.30). These results suggest an α[SUB]2[/SUB] AR agonist might reduce mortality in patients with COVID-19. Randomized controlled trials are needed to confirm this observation.
Keywords: alpha-2 adrenergic receptor agonist; coronavirus disease 2019 (COVID-19); dexmedetomidine; mortality; severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).