**Background:** The COVID-19 pandemic, caused by SARS-CoV-2, has resulted in over 6.88 million deaths and 676 million cases globally as of March 2023. Surgical practice has been severely disrupted, with more than 28 million procedures cancelled in the first 12 weeks of the pandemic. Patients who contract COVID-19 within six weeks after surgery face increased mortality risk, leading to recommendations to delay elective surgery for 4–12 weeks depending on severity and vaccination status. COVID-19 affects not only the pulmonary system but also causes endothelial dysfunction, vascular inflammation, and coagulation changes, increasing risks of deep vein thrombosis, pulmonary embolism, and cerebrovascular accidents. Surgery during active infection is associated with a 10-fold increase in short-term mortality, and approximately half of infected surgical patients experience postoperative pulmonary complications. This correspondence examines the immunopharmacological effects of general anaesthetics and their potential implications for surgical patients during the pandemic.
**Methods:** This is a correspondence article that reviews existing literature on general anaesthetics and their immunomodulatory effects. The authors discuss intravenous agents (propofol, thiopental, ketamine, etomidate) and inhaled volatile anaesthetics (isoflurane, sevoflurane, desflurane, halothane, nitrous oxide), as well as opioids, summarizing their mechanisms of action and reported effects on immune cells.
**Key Results:** Propofol inhibits mouse macrophage chemotaxis and oxidative capacity, as well as ATP and interferon-γ synthesis, but may be less toxic to NK cells, which have antiviral and anticancer properties. In a rat model, propofol did not inhibit NK cells or promote metastases, unlike halothane and ketamine. In human cell models, propofol did not reduce NK cell cytotoxicity, whereas sevoflurane and isoflurane inhibited LFA-1 and reduced NK activity. Etomidate suppresses cell-mediated innate immunity by inhibiting eosinophil chemotaxis in vitro and may increase lymphocyte apoptosis in septic rats; clinical concentrations depress total T-lymphocyte populations. Ketamine inhibits neutrophil chemotaxis by decreasing endothelial adhesion molecule expression and blocks superoxide free-radical generation via reduced NADPH oxidase phosphorylation. It also inhibits monocyte differentiation into immature dendritic cells through NMDA-dependent and TGF-dependent mechanisms. Dexmedetomidine at therapeutic doses had no effect on neutrophil chemotaxis, phagocytosis, or superoxide generation. Volatile anaesthetics target non-canonical immune receptors such as TLR2, TLR4, LFA-1, Mac-1, and Rap1, suppressing neutrophil, monocyte, and macrophage functions. Extended isoflurane exposure impairs neutrophil recruitment and bacterial phagocytosis via reduced LFA-1 and Mac-1 activity. Isoflurane decreases phagocyte ingestion of opsonized and non-opsonized particles in a time-dependent manner. Sevoflurane and desflurane promote apoptosis of thymus T cells, and desflurane induces B lymphocyte apoptosis via IP3 activation. Opioids, particularly morphine, inhibit NK cell cytotoxicity, reduce macrophage- and neutrophil-mediated phagocytosis, inhibit reactive oxygen species generation, and downregulate cytokine synthesis. They also induce apoptosis, impede immune cell proliferation, inhibit T-cell-mediated adaptive responses, diminish B lymphocyte effector response, and increase Th1 cell death and Th2 differentiation.
**Clinical Implications:** The immunosuppressive effects of general anaesthetics may leave patients vulnerable to SARS-CoV-2 infection during and after surgery, potentially exacerbating perioperative complications. The authors emphasize the need for the highest level of precaution when using these agents, especially in the context of the pandemic. They recommend delaying elective surgery for at least 8 weeks after confirmed SARS-CoV-2 infection to reduce the risk of postoperative complications. The absence of alternative medications with better pharmacological properties and fewer immunosuppressive side effects underscores the importance of careful patient selection and timing of surgery.