A Critical Appraisal of the Effects of Anesthetics on Immune-system Modulation in Critically Ill Patients With COVID-19

Chalkias, Athanasios; Barreto, Erin F.; Laou, Eleni; Kolonia, Konstantina; Scheetz, Marc H.; Gourgoulianis, Konstantinos; Pantazopoulos, Ioannis; Xanthos, Theodoros

doi:10.1016/j.clinthera.2021.01.004

Cited by 8 publications

(10 citation statements)

References 119 publications

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“…The effect of different anaesthetics on immunity has been the focus of substantial body of anaesthesiology research 32,33 . Studies have been conducted on patients’ immune status 34–36 . Other investigation has explored whether anaesthesia can inhibit the immune response of patients with cancer, thereby affecting their long‐term outcomes 37,38 .…”

Section: Discussionmentioning

confidence: 99%

“… 32 , 33 Studies have been conducted on patients’ immune status. 34 , 35 , 36 Other investigation has explored whether anaesthesia can inhibit the immune response of patients with cancer, thereby affecting their long‐term outcomes. 37 , 38 Studies have also examined the effects of anaesthetics on the number and apoptosis of immune cells, and some studies have examined the changes in inflammatory factors and oxidative stress levels.…”

Section: Discussionmentioning

confidence: 99%

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An atlas of dynamic peripheral blood mononuclear cell landscapes in human perioperative anaesthesia/surgery

Wang

Chang

Zhu

et al. 2022

Clinical & Translational Med

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Background The number of patients receiving anaesthesia is increasing, but the impact of general anaesthesia on the patient's immune system remains unclear. The aim of the present study is to investigate dynamics of systemic immune cell responses to anaesthesia during perioperative period at a single‐cell solution. Methods The peripheral blood mononuclear cells (PBMCs) and clinical phenomes were harvested and recorded 1 day before anaesthesia and operation, just after anaesthesia (0 h), and 24 and 48 h after anaesthesia. Single‐cell sequencing of PBMCs was performed with 10× genomics. Subsequently, data analysis was performed with R packages: Seurat, clusterProfiler and CellPhoneDB. Results We found that the cluster of CD56+ NK cells changed at 0 h and the cluster of monocytes increased at 24 and 48 h after anaesthesia. The characteristic genes of CD56+ NK cells were mainly enriched in the Jak‐STAT signalling pathway and in cell adhesion molecules (24 h) and carbon metabolism (48 h). The communication between CD14+ monocytes and other cells decreased substantially 0 and 48 h after operation. The number of plasma cells enriched in protein export in men was substantially higher than that in women, although the total number in patients decreased 24 h after operation. CD14+ monocytes dominated that cell‐cell communications appeared in females, while CD8+ NKT cells dominated that cell‐cell communications appeared in male. The number of plasma cells increased substantially in patients with major surgical trauma, with enrichments of pentose phosphate pathway. The communications between plasma cells with other cells varied between surgical severities and anaesthetic forms. The intravenous anaesthesia caused major alterations of cell types, including CD14+ monocytes, plasmas cells and MAIT cells, as compared with inhalation anaesthesia. Conclusion We initially reported the roles of perioperative anaesthesia/surgery in temporal phenomes of circulating immune cells at a single‐cell solution. Thus, the protection against immune cell changes would benefit the recovery from anaesthesia/surgery.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

An atlas of dynamic peripheral blood mononuclear cell landscapes in human perioperative anaesthesia/surgery

Wang

Chang

Zhu

et al. 2022

Clinical & Translational Med

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“…Furthermore, physicians should keep in mind that the heart rate may normalise rapidly within 5 days after the last remdesivir dose. However, in case of deterioration and/or airway management, the potent adverse cardiovascular effects of remdesivir must be taken into account [ 21 , 22 ].…”

Section: Discussionmentioning

confidence: 99%

Remdesivir-induced Bradycardia is not Associated with Worse Outcome in Patients with COVID-19: A Retrospective Analysis

Pantazopoulos

Mavrovounis

Dimeas

et al. 2022

Am J Cardiovasc Drugs

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Background COVID-19, is primarily a respiratory illness but is known to cause extrapulmonary manifestations, especially on the cardiovascular system. Bradycardia is commonly reported in COVID-19 patients despite no prior history of occurrence, and many studies have shown an association with increased mortality. Multiple case reports have been published showcasing remdesivir potentially causing bradycardia. Our aim was to investigate the incidence of bradycardia in patients receiving remdesivir and examine the association with disease severity and survival outcomes. Methods A retrospective study was performed including 160 COVID-19 patients receiving remdesivir for 5 days. Patients’ demographics, comorbidities, medication, vital signs, laboratory tests and outcome were recorded. Bradycardia was defined as a heart rate < 60 beats/min and severe bradycardia < 50 beats/min. Results One hundred eighteen (73.8%) patients experienced at least one episode of bradycardia during hospitalisation. Bradycardia was present in 12 (7.5%) patients before treatment with remdesivir. The rate of bradycardia increased up to the 6th day of hospitalisation (40.6%) and subsequently diminished and normalised within 5 days after the last remdesivir dose (5% at Day 10). Severe bradycardia was observed in 13 (7.5%) patients. No difference was observed in ICU admission between groups (bradycardia vs no bradycardia). When we stratified patients according to the outcome of hospitalisation, no significant difference was observed in the occurrence of bradycardia between groups (alive vs dead) [ p = 0.853]. Conclusions Treatment with remdesivir may be associated with new-onset bradycardia in hospitalised patients with COVID-19. However, bradycardia is transient and is not associated with ICU admission and mortality.

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“…Midazolam may modulate the immune system by binding to the peripheral receptor of macrophages and inhibiting the proinflammatory responses [ 21 ], while ketamine acts at different levels of inflammation, interacting with inflammatory cell recruitment, cytokine production (IL-6, TNF- α ), and regulation of inflammatory mediators [ 12 ], which could explain in-part the nonsignificant increase in white blood cells. Also, propofol exerts inhibitory effects on neutrophil and monocyte function under different physiological and pathological circumstances, while the effects of cisatracurium and fentanyl are diverse in different disease states and must be further studied [ 22 , 23 ].…”

Section: Discussionmentioning

confidence: 99%

Baseline Values and Kinetics of IL-6, Procalcitonin, and TNF-α in Landrace-Large White Swine Anesthetized with Propofol-Based Total Intravenous Anesthesia

Chalkias

Spyropoulos

Γεωργίου

et al. 2021

BioMed Research International

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The baseline levels of various inflammatory mediators and their changes during anesthesia in swine are not known. The aim of this animal study was to measure the baseline values and kinetics of interleukin-6, procalcitonin, and tumor necrosis factor-alpha in healthy Landrace-Large White swine anesthetized with propofol-based total intravenous anesthesia. We included 8 healthy male pigs with an average weight of 19 ± 2 kg (aged 10-15 weeks) that were subjected to propofol-based total intravenous anesthesia for 8 hours. Complete blood count, serum chemistry, and serum levels of interleukin-6, procalcitonin, and tumor necrosis factor-alpha were analyzed, and serum levels were quantified hourly. Blood was also collected for bacterial culturing. Baseline values of interleukin-6 and procalcitonin were 18 pg/ml and 21 ng/ml, respectively, while tumor necrosis factor-alpha was not detectable during collection of baseline samples. A statistically significant difference was observed in interleukin-6 levels between time points ( p < 0.0001 ). Procalcitonin increased with time, but there were no significant differences between time points ( p = 0.152 ). Tumor necrosis factor-alpha increased until the 3rd hour of propofol-based total intravenous anesthesia, while after the 4th hour, it gradually decreased, reaching its baseline undetectable values by the 7th hour ( p < 0.001 ). Our results can serve as the basis for further translational research.

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A Critical Appraisal of the Effects of Anesthetics on Immune-system Modulation in Critically Ill Patients With COVID-19

Cited by 8 publications

References 119 publications

An atlas of dynamic peripheral blood mononuclear cell landscapes in human perioperative anaesthesia/surgery

An atlas of dynamic peripheral blood mononuclear cell landscapes in human perioperative anaesthesia/surgery

Remdesivir-induced Bradycardia is not Associated with Worse Outcome in Patients with COVID-19: A Retrospective Analysis

Baseline Values and Kinetics of IL-6, Procalcitonin, and TNF-α in Landrace-Large White Swine Anesthetized with Propofol-Based Total Intravenous Anesthesia

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