Background: The purpose of this study was to characterize the novel sedative/hypnotic agent HSK3486, a 2,6-disubstituted alkylphenol analogue.Methods: The mechanism of action of HSK3486 was studied in competitive binding assays and whole-cell patch clamp assays. HSK3486 was administered by bolus intravenous injection to dogs and rats, and the loss of righting reflex as well as effects on the cardiovascular and respiratory systems were assessed. The in vitro metabolism of HSK3486 was analyzed by CYP450 genotyping and enzyme inhibition.Results: HSK3486 competed with t-butylbicycloorthobenzoate (TBOB) and t-butylbicyclophosphorothionate (TBPS) for binding to the gamma-aminobutyric acid type A (GABAA) receptor. HSK3486 potentiated GABA-evoked chloride currents at lower concentrations while activating GABAA receptor at higher concentrations. HSK3486 induced hypnosis in rats and dogs, and had a higher therapeutic index than propofol in rats. The hypnotic potency of HSK3486 was approximately 4-5 fold higher than that of propofol. HSK3486 exerted minimal effects on the cardiovascular system.Conclusions: HSK3486 is a positive allosteric regulator and direct agonist of GABAA receptor. It has a promising sedative/hypnotic effect and good in vivo pharmacokinetic properties, which justify further studies towards its clinical application.

Background: Anesthesia airway management is challenging during tracheal resection and reconstruction as these surgical procedures involve the airway. This case series describes four approaches to airway management in patients undergoing tracheal resection and reconstruction and discusses their advantages and disadvantages.Methods: Thirteen patients underwent 1 of the following 4 kinds of airway management techniques during tracheal resection and reconstruction between 2013 and 2019: intubation, intubation with high frequency jet ventilation (HFJV), non-intubation, and venovenous extracorporeal membrane oxygenation (VV-ECMO).Intraoperative variables and postoperative outcomes were compared for the techniques based on our institution's medical electronic database.Results: Intraoperative oxygenation management involved VV-ECMO in 8 patients, intubation in 2 patients, intubation with HFJV in 2 patients, or non-intubation in 1 patient. The lowest peripheral oxygen saturation (SpO 2 ) in 4 patients was below 90%. Three patients were extubated in the operation room after complete recovery of spontaneous respiration. Most patients were admitted to the intensive care unit for further postoperative treatment, except 1 patient who received laryngeal mask airway management without tracheal intubation during surgery. Two patients died, 1 due to severe anastomotic leakage and the other from acute respiratory distress syndrome. In addition, another patient showed complications with oozing from the wound.Conclusions: Our clinical experience suggests that there is no single airway strategy universally suitable for all tracheal surgeries. The choice of airway management strategy is best determined by multifactorial assessment of advantages and disadvantages according to preoperative comorbidities, unique features of the obstructive mass, surgical experience, and patient preference.

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