Tracheal intubation in coronavirus disease 2019 (COVID-19) patients creates a risk to physiologically compromised patients and to attending healthcare providers. Clinical information on airway management and expert recommendations in these patients are urgently needed. By analysing a two-centre retrospective observational case series from Wuhan, China, a panel of international airway management experts discussed the results and formulated consensus recommendations for the management of tracheal intubation in COVID-19 patients. Of 202 COVID-19 patients undergoing emergency tracheal intubation, most were males (n=136; 67.3%) and aged 65 yr or more (n=128; 63.4%). Most patients (n=152; 75.2%) were hypoxaemic (Sao₂ <90%) before intubation. Personal protective equipment was worn by all intubating healthcare workers. Rapid sequence induction (RSI) or modified RSI was used with an intubation success rate of 89.1% on the first attempt and 100% overall. Hypoxaemia (Sao₂ <90%) was common during intubation (n=148; 73.3%). Hypotension (arterial pressure <90/60 mm Hg) occurred in 36 (17.8%) patients during and 45 (22.3%) after intubation with cardiac arrest in four (2.0%). Pneumothorax occurred in 12 (5.9%) patients and death within 24 h in 21 (10.4%). Up to 14 days post-procedure, there was no evidence of cross infection in the anaesthesiologists who intubated the COVID-19 patients. Based on clinical information and expert recommendation, we propose detailed planning, strategy, and methods for tracheal intubation in COVID-19 patients.

Background: We hypothesized that isoflurane has a greater potency to induce neurodegeneration than sevoflurane in the developing brains of neonatal mice based on our previous studies in cell culture. Methods: We treated 7-day-old mice with either 0.75% isoflurane or 1.1% sevoflurane ( approximately 0.5 minimum alveolar concentration) for 6 h and then obtained blood and brain samples at 2 h after the anesthesia treatment for determination of neuroapoptosis in different brain regions and the neurodegenerative biomarker S100beta in the blood. The mechanisms of neurodegeneration induced by isoflurane or sevoflurane were also compared by determining protein expressions of the cell cycle and apoptosis-related proteins. In separate groups, memory and learning ability were evaluated through the use of Morris Water Maze testing in mice at postnatal day 42 after anesthesia treatment at postnatal day 7. Results: Isoflurane but not sevoflurane significantly increased the neurodegenerative biomarker S100beta in the blood. Isoflurane treatments significantly increased apoptosis indicated by the activation of caspase-3 and elevation of poly-(ADP-ribose) polymerase in different brain regions. An equipotent exposure of sevoflurane tended to increase apoptosis in hippocampal and cortex areas but was significantly less potent than isoflurane. Neither isoflurane nor sevoflurane significantly changed protein levels of glyceraldehyde-3-phosphate dehydrogenase, beta-site amyloid beta-precursor protein-cleaving enzyme, and cell cycle regulatory proteins (CDK4, cyclin D1). Isoflurane and sevoflurane at the selected exposures did not significantly alter memory and learning ability. Conclusion: At equipotent exposures, isoflurane has a greater potency than sevoflurane to cause neurodegeneration in the developing brains of neonatal mice.

Background: Isoflurane induces cell apoptosis by an unknown mechanism. The authors hypothesized that isoflurane activates inositol 1,4,5-trisphosphate (IP3) receptors on the endoplasmic reticulum (ER) membrane, causing excessive calcium release, triggering apoptosis. Methods: The authors determined isoflurane-induced cytotoxicity by measuring caspase-3 activity, lactate dehydrogenase release, MTS (3-(4,5-dimethylthiazol-2-yl)-5-(3carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium, inner salt) reduction, and imaging analysis of cell damage markers (annexin V and propidium iodide staining) in different cell types. The authors used the chicken B lymphocyte with a total knock-out of IP3 receptors, PC12 cells with elevated IP3 receptor activity (transfected with L286V presenilin 1), striatal cells with a knock-in of Q111 Huntingtin, and each cell line's corresponding wild-type controls. The authors also measured the isoflurane-evoked changes of calcium concentration in cytosol and/or mitochondria in these cells. Results: Isoflurane induced apoptosis concentration- and time-dependently, and sequentially elevated cytosolic and then mitochondrial calcium in the chicken B-lymphocyte wild-type but not the IP3 receptor total knock-out cells. Thapsigargin, a calcium adenosine triphosphatase inhibitor on ER membranes, induced apoptosis and elevations of calcium in cytosol and mitochondria in both chicken B-lymphocyte wild-type and IP3 receptor total knock-out cells. Isoflurane induced significantly more neurotoxicity and greater calcium release from the ER in L286V PC12 and Q111 Huntingtin striatal cells than in their corresponding wild-type controls, both of which were significantly inhibited by the IP3 receptor antagonist xestospongin C. Conclusion: These findings suggest that isoflurane activates the ER membrane IP3 receptor, producing excessive calcium release and triggering apoptosis. Neurons with enhanced IP3 receptor activity, as in certain cases of familial Alzheimer or Huntington disease, may be especially vulnerable to isoflurane cytotoxicity.

Background: The authors hypothesized that inhalational anesthetics induced cell damage by causing abnormal calcium release from the endoplasmic reticulum via excessive activation of inositol 1,4,5-trisphosphate (IP3) receptors, with isoflurane having greater potency than sevoflurane or desflurane. Methods: The authors treated DT40 chicken B lymphocytes with total IP3 receptor knockout or their corresponding wild-type control cells with equipotent exposure to isoflurane, sevoflurane, and desflurane. The authors then determined the degree of cell damage by counting the percentage of annexin V- or propidium iodide-positively stained cells or measuring caspase-3 activity. They also studied the changes of calcium concentrations in the endoplasmic reticulum, cytosol, and mitochondria evoked by equipotent concentrations of isoflurane, sevoflurane, and desflurane in both types of DT40 cells. Results: Prolonged use of 2 minimal alveolar concentration sevoflurane or desflurane (24 h) induced significant cell damage only in DT40 wild-type and not in IP3 receptor total knockout cells, but with significantly less potency than isoflurane. In accord, all three inhalational anesthetics induced significant decrease of calcium concentrations in the endoplasmic reticulum, accompanied by a subsequent significant increase in the cytosol and mitochondrial calcium concentrations only in DT40 wild-type and not in IP3 receptor total knockout cells. Isoflurane treatment showed significantly greater potency of effect than sevoflurane or desflurane. Conclusion: Inhalational anesthetics may induce cell damage by causing abnormal calcium release from the endoplasmic reticulum via excessive activation of IP3 receptors. Isoflurane has greater potency than sevoflurane or desflurane to cause calcium release from the endoplasmic reticulum and to induce cell damage.