In vivo imaging reveals a synchronized correlation among neurotransmitter dynamics during propofol and sevoflurane anesthesia

General anesthesia is widely applied in clinical practice.However,the precise mechanism of loss of consciousness induced by general anesthetics remains unknown.Here,we measured the dynamics of five neurotransmitters,includingγ-aminobutyric acid,glutamate,norepinephrine,acetylcholine,and dopamine,in the medial prefrontal cortex and primary visual cortex of C57BL/6 mice through in vivo fiber photometry and genetically encoded neurotransmitter sensors under anesthesia to reveal the mechanism of general anesthesia from a neurotransmitter perspective.Results revealed that the concentrations of γ-aminobutyric acid,glutamate,norepinephrine,and acetylcholine increased in the cortex during propofol-induced loss of consciousness.Dopamine levels did not change following the hypnotic dose of propofol but increased significantly following surgical doses of propofol anesthesia.Notably,the concentrations of the five neurotransmitters generally decreased during sevoflurane-induced loss of consciousness.Furthermore,the neurotransmitter dynamic networks were not synchronized in the non-anesthesia groups but were highly synchronized in the anesthetic groups.These findings suggest that neurotransmitter dynamic network synchronization may cause anesthetic-induced loss of consciousness.

Effect of hepatic function on the EC_(50) of midazolam and the BIS_(50) at the time of loss of consciousness

Objective： To explore the effect of hepatic function on loss of consciousness （LOC） and bispectral index （BIS） during sedation with midazolam （MDZ）. Methods： Forty-five patients were assigned to three groups according to their liver function. Thirty of these patients with diagnoses of cholelithiasis were scheduled laparoscopic cholecys- tectomy, including 15 patients with normal liver function （normal group）, and 15 patients with moderately abnormal liver function based on the results of ultrasonic diagnosis of a moderately fatty liver and elevated alanine transaminase levels of less than three times normal （moderate group）. The other 15 patients with end-stage liver disease （severe group） underwent liver transplantation. Each patient was administered MDZ by way of target-controlled infusion to increase the concentration gradually. At the time of LOC, the BIS was recorded and a blood sample was withdrawn for measurement of the concentration of MDZ. The concentration of MDZ （EC50） and the BIS value （BIS50） at which 50% of patients lose consciousness were calculated using logistic regression. Results： At the time of LOC, the EC50 of MDZ and the BIS50 were similar in the normal and moderate groups （P〉0.05）. LOC occurred at a lower EC50 of MDZ and at a higher BIS50 in the severe group, compared with the normal and moderate groups （P〈0.01）. Conclusions： Patients with end-stage liver disease were more sensitive to MDZ and this affected the prediction of their time of LOC following MDZ administration. There were no changes in response in patients with moderately abnormal hepatic function.

Death of Two Military Pilots in Hawk‑108 Fighter Jet Crash

Deaths associated with emergency seat ejection are rare.This is the first case reported in Malaysia since 1980 involving the death of two renowned fighter pilots postejection as safety measures.Ejection mechanism involves several phases which last for splits of seconds.Each phase has its own setback despite serving as a safety mechanism.Both the pilots’death was as a result of the canopy separation,windblast effect,G‑force effect(gravitational force)as well as acceleration effect.High speed and high altitude would have further contributed to the death.