key: cord-0917605-6npr4pvw
authors: Hirota, Kazuyoshi; Lambert, David G.
title: Anaesthesia-related drugs and SARS-CoV-2 infection
date: 2021-04-05
journal: Br J Anaesth
DOI: 10.1016/j.bja.2021.03.026
sha: e3fadfc05dc6af9fa7e46d6943c7196573476ad9
doc_id: 917605
cord_uid: 6npr4pvw

nan

Famotidine is used for prophylaxis for stress ulcesr in the intensive care unit (ICU) and for aspiration pneumonia as an anaesthetic premedication. A recent report [4] suggests that famotidine may improve outcome in COVID-19 patients. Histamine H 2 antagonists may activate the innate immune system to increase the count and bactericidal actions of neutrophils, enhance phagocytosis and decrease adhesion and peroxide production. H 2 antagonists also increase natural killer cell count and cytotoxicity, enhance production of interleukin (IL)-2, IL-13 and TNFα, expression of MHC-2 and caspase-1 in macrophages/monocytes, and increase MHC-1, CD40, CD80, CD89 and IL-12 in dendritic cells [5] . Although these mechanism(s) have the potential to produce antiviral actions, this will require rigorous experimental evaluation. In contrast, and as shown in a metanalysis, PPIs may aggravate COVID-19 as there was an association between current PPI use and incidence of SARS-CoV-2 infection and severity of COVID-19 when a Korean study was excluded [6] .

Propofol: ACE2 may be upregulated when tissues are exposed to sedative concentrations (10 g ml -1 ) for > 6 h [7] . Propofol might inhibit SARS-CoV-2 entry as suggested for hydroxychloroquine [8] . In addition, clinically relevant concentrations of propofol may have Sig-1R antagonistic properties [7] . Moreover, propofol has both anti-oxidant and anti-inflammatory actions and may reduce systemic inflammation and exert organ protection in COVID-19 [7] .

Ketamine: Ketamine may interact with both Sig-1R and Sig-2R as an agonist. However, its J o u r n a l P r e -p r o o f affinity for Sig-1R (K i =140 M) and Sig-2R (K i =26 M) were in the supra-clinical and clinical ranges, respectively [9] . As Sig-1R is the more important target in SARS-CoV-2 infection[2], it is unlikely that ketamine exerts potent pro-viral actions. However, as ketamine has anti-inflammatory actions, this agent may reduce the risk of SARS-CoV-2-induced cytokine storm [10] .

Haloperidol and droperidol: Clinically relevant concentrations of haloperidol, a butyrophenone that interacts with both Sig-1R and Sig-2R (K i =0.33 nM and 26 nM, respectively) [11] with antagonist effects to produce SARS-CoV-2 antiviral actions[2].

Droperidol, another butyrophenone, interacts with Sig-1R as an antagonist but with a K i of 0.17 M, which exceeds clinically relevant concentrations [12] .

agonist, binding with a K i of 5.7 M [12] which exceeds clinically relevant concentrations [13] .

Dexmedetomidine is therefore unlikely to affect SARS-CoV-2 infection via Sig-1R. However, the anti-inflammatory and organ protective effects of dexmedetomidine [14] may provide therapeutic advantages for COVID-19 patients with multi-organ dysfunction in ICU. The mechanism may hypothetically be due to inhibition of NETosis to prevent immune activation in COVID-19 [14] . Indeed, Stockton and colleagues[15] reported a case of dexmedetomidine improving oxygenation and avoidance of tracheal intubation in a patient with progressive hypoxaemia.

Nitrous oxide, a Sig-R agonist [16] , might aggravate SARS-CoV-2 infection via Sig-R interaction. Regarding volatile anaesthetic agents, there are no reports detailing an interaction J o u r n a l P r e -p r o o f with ACE2 or Sig-R. A COV ID-19 case series showed that isoflurane provided sufficient sedation and significant improvement in oxygenation without any adverse events [17] .

Local anaesthetic agents COV ID-19 patients often show high serum levels of citrullinated histone H3 (Cit-H3) which is a biomarker of NETosis. As serum from COV ID-19 patients induces neutrophil extracellular traps (NETs) release from control neutrophils, COV ID-19 may create a cellular environment for promotion of NETosis. Intravenous lidocaine reduces blood neutrophil myeloperoxidase and Cit-H3 [18] ; this has the potential to attenuate an associated immunological storm [19] .

Although chronic use or misuse of opioids leading to immunosuppression might increase the risk of SARS-CoV-2 infection [20] , opioids may attenuate respiratory symptoms in COV ID-19 patients such as shortness of breath and cough [21] . Moreover, opioids used in substitution therapy may aid in the maintenance of antioxidant capacity [21] . Opioids have the potential to exert both ' theoretical' beneficial and detrimental actions; further evaluation is required.

The World Health Organization (WHO) initially recommended that ibuprofen and other non-steroidal anti-inflammatory drugs (NSA IDs) should be avoided in the management of 

It has been repo rted that  2 -adrenergic recepto r activatio n pro duces anti-inflammato ry actio ns and suppress immune functio n to impair bacterial clearance [24] . Vaso active agents with a  2 -adrenergic pro file po ssess a theo retical risk fo r SA RS-Co V-2 pro liferatio n. 

A ir co ntaminatio n with SA RS-Co V -2 in the o perating ro o m

Famotidine against SARS-CoV2: a hope or hype?

Do proton pump inhibitors influence SARS-CoV-2 related outcomes? A meta-analysis

Propofol and SARS-CoV-2 infection

Putative antiviral effects of propofol in COV ID-19

Ketamine and ketamine metabolite pharmacology: insights into therapeutic mechanisms

Consider adjunctive ketamine in mechanically ventilated COV ID-19 patients

Evaluatio n o f the effects o f the enantio mers o f reduced halo perido l, azapero l, and related 4-amino -1-arylbutano ls o n do pamine and sigma recepto rs

Pro po fo l acts at the sigma-1 recepto r and inhibits pentazo cine-induced c-Fo s expressio n in the mo use po sterio r cingulate and retro splenial co rtices

Co mparative analgesic and mental effects o f increasing plasma co ncentratio ns o f dexmedeto midine and alfentanil in humans

Dexmedeto midine: ano ther arro w in the quiver to fight COV ID-19 in intensive care units

Dexmedeto midine and wo rsening hypo xemia in the setting o f COV ID-19: A case repo rt. A m

A nalgesic (sub anesthetic) nitro us o xide interacts with the endo geno us o pio id system: a review o f the evidence

Vo latile iso flurane in critically ill co ro navirus disease 2019 patients-a case series and systematic review

Neutrophil extracellular trapping and angiogenesis biomarkers after intravenous or inhalation anaesthesia with or without intravenous lidocaine for breast cancer surgery: a prospective, randomised trial

A novel role for lidocaine in COV ID-19 patients?

Opioids and the COV ID-19 pandemic: does chronic opioid use or misuse increase clinical vulnerability?

Does opioid substitution treatment have a protective effect on the clinical manifestations of COV ID-19?

Ibuprofen use and clinical outcomes in COV ID-19 patients