Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Comment
. 2021 Jan;126(1):e35-e38.
doi: 10.1016/j.bja.2020.10.010. Epub 2020 Oct 14.

Dexmedetomidine: another arrow in the quiver to fight COVID-19 in intensive care units

Amit Jain  1 , Massimo Lamperti  2 , D John Doyle  3
Affiliations
Comment

Dexmedetomidine: another arrow in the quiver to fight COVID-19 in intensive care units

Amit Jain et al. Br J Anaesth. 2021 Jan.
No abstract available

Keywords: COVID-19; ICU; NETosis; dexmedetomidine; inflammation; sedation.

PubMed Disclaimer

Conflict of interest statement

Declarations of interest The authors declare that they have no conflicts of interest.

Figures

Fig. 1
Fig. 1
Putative mechanisms of feedforward interactions between neutrophils, macrophages, and organ-specific cells potentiating NETosis during severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, and molecular mechanisms of organ protective and anti-inflammatory effects of dexmedetomidine. SARS-CoV-2 uses ACE-2 as its cell entry receptor and activates MAVS that stimulate viral-infected cells to secrete cytokines by activating NF-κB/STAT signalling pathways. SARS-CoV-2 infection results in NLRP3 inflammasome activation, and aggravates pyroptosis and production of DAMPs, such as HMGB1, that play potential key roles in establishing feedforward interactions between neutrophils, macrophages, and organ cells potentiating NETosis and pyroptosis during SARS-CoV-2 infection. Dexmedetomidine inhibits HMGB1/TLR and HMGB1/RAGE-mediated NETosis. Dexmedetomidine-mediated inhibition of NLPRP3 inflammasome, NF-κB, and JAK/STAT signalling pathways, and activation of cholinergic pathways confers anti-inflammatory and organ-protective effects and may reduce oxidative-stress-mediated pyroptosis and thrombotic complications of COVID-19 disease. Dexmedetomidine inhibits mt-ROS and may thereby prevent SARS-CoV-2-triggered mt-ROS production and stabilisation of HIF-1α and consequent sustained aerobic glycolysis mediating cytokine storm and inflammation. AC, adenylyl cyclase; ACE-2, angiotensin-converting enzyme 2; AMPK, adenosine monophosphate-activated protein kinase; cAMP, cyclic adenosine monophosphate; Cit. H3 histone, citrullinated H3 histone; COVID-19, coronavirus disease 2019; CREB, cyclic adenosine monophosphate response element-binding protein; CTACK, cutaneous T cell-attracting chemokine; DAMP, damage-associated molecular pattern; DEX, dexmedetomidine; G-CSF, granulocyte colony-stimulating factor; GM-CSF, granulocyte–monocyte colony-stimulating factor; GSK-3β, glycogen synthase kinase 3 beta; HIF-1α, hypoxia-inducible factor-1α; HMGB1, high-mobility group box 1; IκB, inhibitor of nuclear factor-κB; IKK complex, inhibitor of nuclear factor-κB kinase; IL1α, interleukin 1α; IL-1β, interleukin 1β; IL6, interleukin 6; IL-7, interleukin 7; IL8, interleukin 8; IL12, interleukin 12; IL-17, interleukin 17; IL-18, interleukin 18; iNOS, inducible nitric oxide synthase; JAK/STAT, Janus kinase/signal transducers and activators of transcription; LL-37, cathelicidin antimicrobial peptide; MAPK, mitogen-activated protein kinase; MAVS, mitochondrial antiviral-signalling protein; MCP-1, monocyte chemoattractant protein-1; MCP-3, monocyte chemoattractant protein-3; MPO, myeloperoxidase; My-D88, myeloid differentiation primary response 88; NE, neutrophil elastase; NET, neutrophil extracellular t rap; NF-κB, nuclear factor kappa light chain enhancer of activated B cells; NLRP3, nod-like receptor family pyrin domain-containing protein 3; PAMP, pathogen-associated molecular pattern; p-Akt, phosphorylated protein kinase B; PI3K, phosphoinositide 3-kinases; P-JNK, phophorylated c-Jun N-terminal kinases; PKA, cyclic adenosine monophosphate-dependent protein kinase; PRR, pattern recognition receptor; P2X7R, P2X purinoceptor 7; RAGE, receptors for advanced glycation end-products; mt-ROS, mitochondrial reactive oxygen species; Th17, T-helper (Th) cell 17; TLR, toll-like receptor; TRAF6, tumor necrosis factor receptor associated factor 6; TNFα, tumor necrosis factor-alpha; α2AR, α2-adrenenergic receptor; α7 nAChR, α7-nicotinic acetylcholine receptor.
See this image and copyright information in PMC

Comment in

Comment on

  • A novel role for lidocaine in COVID-19 patients?
    Finnerty DT, Buggy DJ. Finnerty DT, et al. Br J Anaesth. 2020 Oct;125(4):e391-e394. doi: 10.1016/j.bja.2020.07.015. Epub 2020 Jul 23. Br J Anaesth. 2020. PMID: 32792138 Free PMC article. No abstract available.

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Finnerty D.T., Buggy D.J. A novel role for lidocaine in COVID-19 patients? Br J Anaesth. 2020;125 e391–4. - PMC - PubMed
    1. Pandharipande P.P., Pun B.T., Herr D.L., et al. Effect of sedation with dexmedetomidine versus lorazepam on acute brain dysfunction in mechanically ventilated patients: the MENDS randomized controlled trial. JAMA. 2007;298:2644–2653. - PubMed
    1. Zhang Z., Chen K., Ni H., Zhang X., Fan H. Sedation of mechanically ventilated adults in intensive care unit: a network meta-analysis. Sci Rep. 2017;7:44979. - PMC - PubMed
    1. Pandharipande P.P., Sanders R.D., Girard T.D., et al. Effect of dexmedetomidine versus lorazepam on outcome in patients with sepsis: an a priori-designed analysis of the MENDS randomized controlled trial. Crit Care. 2010;14:R38. - PMC - PubMed
    1. Kawazoe Y., Miyamoto K., Morimoto T., et al. Effect of dexmedetomidine on mortality and ventilator-free days in patients requiring mechanical ventilation with sepsis: a randomized clinical trial. JAMA. 2017;317:1321–1328. - PMC - PubMed