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Background: Propofol is an i.v. anaesthetic commonly used during general anaesthesia and intensive care. It is known that the second transmembrane segment of the beta subunit in the GABA(A) receptor is an important target for the effects of propofol; however, this has not been investigated in human receptors. The aim of this study was to investigate the effect of propofol on human beta2 and beta3 GABA(A) subunits with point mutations corresponding to the N265M mutation in the rat beta2 and beta3 subunits.Methods: Asparagine-to-methionine replacement at amino acid position 289 and 290 (N289M and N290M) in the beta2 and beta3 GABA(A) receptor subunits, respectively, was accomplished by site-directed mutagenesis. Thereafter, subunits for three human wild-type (alpha1beta2gamma2, alpha2beta2gamma2, and alpha2beta3gamma2) and two mutant GABA(A) receptor channels [alpha1beta2(N289M)gamma2 and alpha2beta3(N290M)gamma2] were introduced into Xenopus oocytes and studied with two-electrode voltage clamp.Results: The mutant receptors left-shifted the GABA concentration-response curve. In comparison with the wild-type receptors, both the positive modulatory and the agonistic effects of propofol were strongly reduced in potency and amplitude at both mutated GABA(A) channels.Conclusions: We demonstrate that N289M or N290M mutation in human GABA(A) beta2 and beta3 subunits increases sensitivity to GABA, which is in contrast to the corresponding rat N265M mutation. Furthermore, the N289M and N289M mutations reduce both the potentiation of GABA-induced currents and the direct effect of propofol on channels incorporating either of the mutated subunits, which confirms earlier findings concerning the corresponding mutation in rat receptors and knock-in mice. [ABSTRACT FROM AUTHOR]

Background.: Apnoeic oxygenation during anaesthesia has traditionally been limited by the rapid increase in carbon dioxide and subsequent decrease in pH. Using a Transnasal Humidified Rapid-Insufflation Ventilatory Exchange (THRIVE) technique a slower increase in carbon dioxide than earlier studies was seen. Notably, apnoeic oxygenation using THRIVE has not been systematically evaluated with arterial blood gases or in patients undergoing laryngeal surgery. The primary aim of this study was to characterize changes in arterial P O 2 , P CO 2 and pH during apnoeic oxygenation using THRIVE under general anaesthesia.Methods.: Adult patients, (ASA I-II), undergoing shorter laryngeal surgery under general anaesthesia, were oxygenated during apnoea using THRIVE, 100% oxygen, 40-70 litres min - 1 . A cohort was randomized to hyperventilate during pre-oxygenation. Vital parameters and blood gases were monitored.Results.: Thirty-one patients, age 51 (34-76) yr, BMI 25 (4) were included. Mean apnoea time was 22.5 (4.5) min. Patients were well oxygenated, S pO 2 was never below 91%. The increase in P aCO 2 and end-tidal CO 2 during apnoea was 0.24 (0.05) and 0.12 (0.04) kPa min -1 , respectively. Hyperventilation during pre-oxygenation generated no difference in P aCO 2 at the end of apnoea compared with normoventilation.Conclusions.: This physiological study of apnoeic oxygenation using THRIVE during laryngeal surgery shows that this technique is able to keep patients with mild systemic disease and a BMI <30 well oxygenated for a period of up to 30 min. The THRIVE concept makes it possible to extend the apnoeic window but monitoring of CO 2 and/or pH is recommended.Clinical Trial Registration.: NCT02706431. [ABSTRACT FROM AUTHOR]