key: cord-0846686-v0qbzewp
authors: Zhao, Hailin; Davies, Roger; Ma, Daqing
title: Potential therapeutic value of dexmedetomidine in COVID-19 patients admitted to ICU
date: 2020-10-02
journal: Br J Anaesth
DOI: 10.1016/j.bja.2020.09.031
sha: 3e7b165785ed9463fe4527127f4cad30c937f617
doc_id: 846686
cord_uid: v0qbzewp

nan

Hailin Zhao 1 Editor -The COVID-19 pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is an ongoing global health concern 1 that has so far caused > 29 million infections and resulted in more than 900,000 deaths worldwide.

The clinical manifestations of COVID-19 range from asymptomatic infection to severe acute respiratory failure and multi-organ dysfunction requiring organ supportive therapy such as mechanical ventilation in the intensive care unit (ICU). Once established, multi-organ dysfunction is associated with reduced patient survival and quality of life following ICU discharge 2 . There is a pressing need to understand the disease mechanisms underlying COVID-19 in order to develop novel therapeutic strategies to improve patient survival.

Overwhelming immune activation resulting in a "cytokine storm" as well as systemic hypoxaemia due to pulmonary dysfunction may lead to cell death within vital organs, including brain, lung, kidney, liver and gut and are thought to contribute to the MOD and poor outcomes in COVID-19 2 . Whilst a number of therapeutic approaches have been proposed or trialled to modulate the dysregulated immune response in COVID-19, thus far only dexamethasone, a potent glucocorticoid steroid with broad J o u r n a l P r e -p r o o f effects on innate and adaptive immunity, has been shown to improve patient survival.

Accumulating data show that cell necrosis and necroptosis (programmed cell death)

are key cell death mechanisms implicated in both acute organ injury and chronic inflammatory disease 3 . When lung alveolar cells and/or lung macrophages become infected with SARS-CoV-2, resultant cell death may result in widespread immune cell activation through activation of pattern recognition receptors on innate immune cells.

The therapeutic efficacy of antiviral therapies such as remdesivir 4 , a nucleotide analogue that inhibits viral RNA polymerase, or lopinavir/ritonavir, a viral protease inhibitor combination used for HIV-1 treatment, remains to be verified. Targeting angiotensin-converting enzyme 2 (ACE2) 5 Furthermore, preserving the alveolar capillary interface, which provides an anatomical barrier, may prevent secondary bacterial infection associated with SARS-CoV-2.

The potent and selective α 2 -adrenoceptor agonist dexmedetomidine exerts sedative and analgesic effects and has been widely used as an adjunct for anaesthesia, analgesia and sedation in the ICU 6 . In addition, dexmedetomidine has both cytoprotective and anti-inflammatory properties. 6a In fact, its organoprotective effects against acute organ injury, such as brain 7 , lung and kidney 8 The subsequent cell death, cytokine storm and systemic hypoxaemia due to pulmonary dysfunction/failure are considered to be the pathogenesis of MOD/MOF which includes neurological dysfunction, acute kidney and liver injury, myocardial dysfunction. Dexmedetomidine (DEX) has potent protective effects through up-regulating protective proteins and attenuating cell death and systemic inflammation, and, thereby may protect vital organs from MOD/MOF in COVID-19 patients who require sedation and mechanical ventilation in the ICU. In addition, its cholinergic anti-inflammatory mechanisms can suppress excessive inflammatory responses and its anti-oxidative effects preserve cells away from oxidative stress additional benefits to COVID-19 patients irrespective of other supportive treatments currently available.

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