Etomidate protects retinal ganglion cells from hydrogen peroxide-induced injury via Nrf2/HO-1 pathway

AIM:To determine whether etomidate(ET)has a protective effect on retinal ganglion cells(RGCs)injured with hydrogen peroxide(H_(2)O_(2))and to explore the potential mechanism underlying the antioxidative stress effect of ET.METHODS:Cultured RGCs were identified by double immunofluorescent labeling of microtubule-associated protein 2 and Thy1.1.An injury model of H_(2)O_(2)-induced RGCs oxidative stress was established in vitro.Cells were pretreated with different concentrations of ET(1,5,and 10μmol/L)for 4h,followed by further exposure to H_(2)O_(2)at 1000μmol/L.Cell counting kit 8 and Annexin V/propidium iodide assays were applied to detect the viabilities and apoptosis rates of the RGCs at 12,24,and 48h after H_(2)O_(2)stimulation.The levels of nitric oxide,malondialdehyde,and glutathione in culture media were measured at these time points.Quantitative reverse transcription polymerase chain reaction(qRT-PCR)and Western blot were performed to observe the effects of ET on the messenger RNA and protein expression of inducible nitric oxide synthase(iNOS),nuclear factor erythroid 2-related factor 2(Nrf2),heme oxygenase 1(HO-1),glutathione peroxidase 1 and the level of conjugated acrolein in RGCs at 12,24,and 48h after H_(2)O_(2)stimulation and in the retina at 12h after optic nerve transection(ONT).RESULTS:The applications of 5 and 10μmol/L of ET significantly increased the viability of RGCs.Results from qRT-PCR indicated a decrease in the expression of iNOS and an increase in the expressions of Nrf2 and HO-1 in ETpretreated RGCs at 12,24 and 48h after H_(2)O_(2)stimulation,as well as in ET-treated retinas at 12h after ONT.Western blot analysis revealed a decrease in the expression of iNOS and levels of conjugated acrolein,along with an increase in the expressions of Nrf2 and HO-1 in ET-pretreated RGCs in vitro and ET-treated retinas in vivo.CONCLUSION:ET is a neuroprotective agent in primary cultured RGCs injured by H_(2)O_(2).The effect of ET is dosedependent with the greatest effect being at 10μmol/L.ET plays an antioxidant role by inhibiting iNOS,up-regulating Nrf2/HO-1,decreasing the production of acrolein,and increasing the scavenge of acrolein.

Etomidate affects the anti-oxidant pathway to protect retinal ganglion cells after optic nerve transection

Our previous studies revealed that etomidate, a non-barbiturate intravenous anesthetic agent, has protective effects on retinal ganglion cells within 7 days after optic nerve transection. Whether this process is related to anti-oxidative stress is not clear. To reveal its mechanism, we established the optic nerve transection injury model by transecting 1 mm behind the left eyeball of adult male Sprague-Dawley rats. The rats received an intraperitoneal injection of etomidate(4 mg/kg) once per day for 7 days. The results showed that etomidate significantly enhanced the number of retinal ganglion cells retrogradely labeled with Fluorogold at 7 days after optic nerve transection. Etomidate also significantly reduced the levels of nitric oxide and malonaldehyde in the retina and increased the level of glutathione at 12 hours after optic nerve transection. Thus, etomidate can protect retinal ganglion cells after optic nerve transection in adult rats by activating an anti-oxidative stress response. The study was approved by the Animal Ethics Committee at Air Force Medical University, China(approval No. 20180305) on March 5, 2018.

Etomidate vs propofol in coronary heart disease patients undergoing major noncardiac surgery:A randomized clinical trial

BACKGROUND The ideal depth of general anesthesia should achieve the required levels of hypnosis,analgesia,and muscle relaxation while minimizing physiologic responses to awareness.The choice of anesthetic strategy in patients with coronary heart disease(CHD)undergoing major noncardiac surgery is becoming an increasingly important issue as the population ages.This is because general anesthesia is associated with a risk of perioperative cardiac complications and death,and this risk is much higher in people with CHD.AIM To compare hemodynamic function and cardiovascular event rate between etomidate-and propofol-based anesthesia in patients with CHD.METHODS This prospective study enrolled consecutive patients(American Society of Anesthesiologists grade II/III)with stable CHD(New York Heart Association class I/II)undergoing major noncardiac surgery.The patients were randomly allocated to receive either etomidate/remifentanil-based or propofol/remifentanil-based general anesthesia.Randomization was performed using a computer-generated random number table and sequentially numbered,opaque,sealed envelopes.Concealment was maintained until the patient had arrived in the operating theater,at which point the consulting anesthetist opened the envelope.All patients,data collectors,and data analyzers were blinded to the type of anesthesia used.The primary endpoints were the occurrence of cardiovascular events(bradycardia,tachycardia,hypotension,ST-T segment changes,and ventricular premature beats)during anesthesia and cardiac troponin I level at 24 h.The secondary endpoints were hemodynamic parameters,bispectral index,and use of vasopressors during anesthesia.RESULTS The final analysis included 40 patients in each of the propofol and etomidate groups.The incidences of bradycardia,hypotension,ST-T segment changes,and ventricular premature beats during anesthesia were significantly higher in the propofol group than in the etomidate group(P<0.05 for all).The incidence of tachycardia was similar between the two groups.Cardiac troponin I levels were comparable between the two groups both before the induction of anesthesia and at 24 h after surgery.When compared with the etomidate group,the propofol group had significantly lower heart rates at 3 min after the anesthetic was injected(T1)and immediately after tracheal intubation(T2),lower systolic blood pressure at T1,and lower diastolic blood pressure and mean arterial pressure at T1,T2,3 min after tracheal intubation,and 5 min after tracheal intubation(P<0.05 for all).Vasopressor use was significantly more in the propofol group than in the etomidate group during the induction and maintenance periods(P<0.001).CONCLUSION In patients with CHD undergoing noncardiac major surgery,etomidate-based anesthesia is associated with fewer cardiovascular events and smaller hemodynamic changes than propofol-based anesthesia.

General Anesthesia with Laryngeal Mask Airway: Etomidate VS Propofol for Hemodynamic Stability

Background: Propofol is the most popular induction agent for laryngeal mask airway (LMA) insertion in current anaesthesia practice however associated hypotension has been reported as its major disadvantage. Etomidate, which produces less hypotension, can be considered as an alternative agent for LMA insertion. Objectives: The objective of this study was to compare the hemodynamic effects of etomidate with propofol for induction of general anaesthesia (GA) for LMA. Ease of inserting LMA was also looked at. Material and Methods: It was a prospective randomized double blinded study. All ASA I and II patients of 15 - 60 years of age undergoing general anaesthesia with LMA for elective surgeries were included. Patients were induced with intravenous (I/V) fentanyl and induction agent either etomidate or propofol according to group randomization. LMA was inserted after 30 seconds. Intra-operative heart rate (HR), sys tolic blood pressure (SBP), diastolic blood pressure (DBP), mean arterial pressure (MAP), number of attempts and duration of LMA insertion were monitored. Results: There was no difference in the heart rate between the two groups. A significant drop was found for systolic blood pressure (SBP) in propofol group while diastolic blood pressure (DBP) was decreased in both the groups. In propofol group, successful insertion of LMA was achieved on the first attempt in 93.3% of patient as compared to 36.7% in etomidate group. Conclusion: Use of etomidate for induction of laryngeal mask anesthesia can prevent the hypotension following induction;however it may delay the insertion of laryngeal mask airway.

Influence of propofol or etomidate combined with remifentanil in painless gastroscopy on inflammatory stress response

Objective:To study the influence of propofol or etomidate combined with remifentanil in painless gastroscopy on inflammatory stress response.Methods: 117 patients with suspected gastritis who underwent painless gastroscopy in our hospital between July 2015 and August 2016 were divided into propofol group (n=67) and etomidate group (n=50) according to the anesthesia schemes. Propofol group received propofol combined with remifentanil anesthesia, and etomidate group received etomidate combined with remifentanil anesthesia. The differences in serum levels of inflammatory factors, stress hormones and oxidative stress indicators were compared between the two groups before the examination (T0), immediately after the examination (T1) and 15 min after the examination (T2).Results: At T0, there were no significant differences in serum levels of inflammatory factors, stress hormones or oxidative stress indexes between the two groups (P>0.05). At T1 and T2, serum inflammatory factors IL-1, IL-6 and CRP levels of etomidate group were lower than those of propofol group;serum stress hormones Cor, NE and E levels were lower than those of propofol group;serum oxidation indexes AOPPs and LHP levels were lower than those of propofol group while anti-oxidation indexes CAT and SOD levels were higher than those of propofol group (P<0.05). Conclusion: Etomidate for painless gastroscopy is better than propofol in maintaining depth of anesthesia and reducing operation trauma.

Clinical Observation of Dexmedetomidine Combined with the Mixture of Propofol and Etomidate on Painless Gastroscopy in Children

Objective:To observe the anesthetic effect of dexmedetomidine combined with the mixture of propofol and etomidate on painless gastroscopy in children.Methods:A total of 80 pediatric patients who underwent painless gastroscopy in the Guangxi Minzu Hospital from January 2019 to September 2020 were randomly divided into two groups,A and B,with 40 patients in each group.Group A was given A mixture of etomidate 20 mg and propofol 0.2g,Dexmedetomidine was pumped into group B 10min before surgery,0.4 g/kg.HR,SBP,DBP,SpO2 and BIS were continuously monitored after entering the room.The doses of propofol and etomidate were recorded,as well as the time of waking and leaving the hospital.Adverse reactions such as hypotension,hypoxemia,nausea,vomiting and dizziness were recorded too.Results:Compared with group A,the dosage of propofol and etomidate in group B was significantly reduced(P<0.001),the time of waking and out of the chamber were significantly shortened(P<0.001),the body movement in the incidence of intraoperative was significantly reduced(P<0.001),and the nausea,vomiting and dizziness in the incidence of postoperative were significantly reduced(P<0.05).Conclusion:Dexmedetomidine combined with propofol and etomidate mixture can be safely used in painless gastroscopy in children,which can significantly reduce the dosage of propofol and etomidate,reduce the occurrence of adverse reactions,and shorten the time of resuscitation and discharge.

Bidirectional regulation of intravenous anes⁃thetic etomidate on TREK-1 potassium channel

OBJECTIVE Two-pore domain potassium channel subtype TREK-1 was widely proved to be activated by inhalational anesthet⁃ics such as chloroform,diethyl ether,halothane,and isoflurane.But little is known about whether TREK-1 was also a potentially important target of intravenous anesthetics.Etomidate is a popularly used intravenous anesthetic with good safety in clinic.The action of etomidate on TREK-1 was seldom reported.METHODS AND RESULTS By using patch-clamp whole-cell recording tech⁃niques,we found for the first time that etomidate could bidirectionally regulate the TREK-1 potassi⁃um channel in CHO/TREK-1 cells.TREK-1 current amplitudes were observed after the administra⁃tion of etomidate at concentrations ranging from 3 to 100μmol·L-1.Etomidate activated TREK-1 current at concentrations of 3,10,and 15μmol·L-1 with maximum activation at 10μmol·L-1.Interest⁃ingly,at higher concentrations from 20 to 100μmol·L-1,etomidate inhibited TREK-1 current in a concentration-dependent way.According to the concentration-response curve,the fitted criti⁃cal concentration of etomidate between TREK-1 activation and inhibition was 20.7μmol·L-1,which close to the result that etomidate had no obvious effect on TREK-1 at 20μmol·L-1.In addition,etomidate 10μmol·L-1 induced a significant mem⁃brane potential hyperpolarization while etomidate 30μmol·L-1 showed obvious membrane potential depolarization.Furthermore,the bidirectional regulation still existed when the extracellular pH of CHO/TREK-1 cells was decreased.CONCLUSION TREK-1 is activated by etomi⁃date at clinically relevant concentrations but inhib⁃ited by supraclinical concentrations of etomidate,which is different to other volatile anesthetics.TREK-1 might be a potential target for anesthetic such as etomidate and the complicated bidirec⁃tional regulation mechanism of etomidate needed to be fully studied in the future.

[Ca^(2+)]_i change in hippocampal neurons influenced by preconditioning of etomidate fat emulsion following cerebral ischemia in rats

BACKGROUND： It is known that intravenous anesthetic etomidate fat emulsion has cerebral protection. Now many scholars focus on the research of its cerebral protection from molecular biology, but the mechanism of cerebral protection is still fully unclear. OBJECTIVE： To observe the influence of etomidate fat emulsion on the [Ca^2＋]i in hippocampal neurons during the transient cerebral ischemia injury in rats. DESIGN： Randomized controlled observation. SETTING： Weifang Medical College. MATERIALS： This study was carried out in the functional laboratory of Weifang Medical College between October 2005 and March 2006. Twenty-four male healthy Wistar rats, aged 3 to 4 months, were involved. Etomidate fat emulsion was provided by the limited company of En-hua Medical Bloc in Jiangsu Province （code of H200205l l） and the other agents and materials were provided by Laboratory Center of Weifang Medical College. METHODS： The 24 Wistar rats were randomized into 3 groups： sham-operation group, model group and etomidate preconditioning group, with 8 rats in each. Rat models of transient cerebral ischemia injury were made by the ligation of bilateral carotid arteries combined with descending blood pressure in the latter two groups. Before ischemia （ligation of bilateral common carotid artery）, rats in the etomidate preconditioning group were intraperitoneally injected with 12 mg/kg etomidate fat emulsion and then persistently intraperitoneally injected with etomidate fat emulsion at 1.0 mg/kg per minute. Rats in the model group were not administrated. Rats in the sham-operation group were only performed bilateral common carotid artery isolation. When rats were modeled, their brain tissues were quickly taken out and detected. MAIN OUTCOME MEASURES： Change of the fluorescence pixel value of the [Ca^2＋]i in each group by the laser scanning confocal microscope. RESULTS： Twenty-four rats were involved in the final analysis. Fluorescence pixel value in the sham-operation group was in the low level. Fluorescence pixel value in the model group was significantly higher than that in the sham-operation group （P 〈 0.01）. Fluorescence pixel value in the etomidate preconditioning group was significantly lower than that in the model group （P 〈 0.01 ）. CONCLUSION： The protection of etomidate fat emulsion to the transient cerebral ischemic injury in rats is associated with the inhibition to the increase of [Ca^2＋]i to some extent.

Determination of enantiomeric impurity of etomidate by high performance liquid chromatography

Objective To determine enantiomeric impurity of etomidate using high performance liquid chromatography. Methods (R)-etomidate and (S)-etomidate were separated on a CHIRALPAK AD-H column. The mobile phase consisted of 20∶80(v/v) isopropanol-n-hexane. The flow rate of the mobile phase was 0.5mL/min. The detected wavelength was 242nm. Results (R)-etomidate and (S)-etomidate could be separated completely under these conditions. The precision of (R)-etomidate was 1.57% (n=3). The limit of detection of (R)-etomidate was 4.25ng/mL. The average percentage content of (S)-etomidate was 0.09% in the samples. Conclusion The method was repeatable and sufficiently sensitive to determine the enantiomeric impurity of etomidate. It allows the quantitation of the impurities at the 0.085% (w/w) level relative to etomidate at a concentration of the test solution of 5mg/mL.

Retrospective Review of Propofol versus Etomidate during Rapid Sequence Intubation in the Emergency Department at a Tertiary Academic Center

Background: Etomidate is the standard induction agent used during rapid sequence intubation (RSI) in the emergency department (ED). Etomidate shortages require providers to utilize alternative agents. The purpose of this study is to compare the safety and procedural outcomes of propofol and etomidate for RSI in the ED. Methods: This was a retrospective chart review of adult patients in the ED who received propofol or etomidate for induction during RSI. The main endpoint was hypotension, defined as a systolic blood pressure < 90 mmHg or diastolic blood pressure < 60 mmHg, within the first hour of intubation. Time to intubation, intensive care unit length of stay, hospital length of stay, and in-hospital mortality were also evaluated. Results: Two hundred and seventy five patient charts were reviewed. Of the 98 patients included, 43 patients received propofol and 55 patients received etomidate. Propofol was associated with an increased incidence of hypotension within the first hour of intubation (65.1% vs. 25.5%, p < 0.001). No difference was found in the time to intubation: ≤5 minutes (51.2% vs. 34.6%, p = 0.83). The mortality rate was 11.6% in the propofol group and 27.3% in the etomidate group (p = 0.004). There was no difference in hospital or intensive care unit length of stay between the propofol and etomidate groups (7.7 vs. 9.2 days, p = 0.23;4.2 vs. 6.3 days, p = 0.31). Conclusion: Propofol was a safe and procedurally effective induction agent for RSI. Compared to etomidate, it was associated with an increased rate of hypotension within the first hour of intubation, with no difference in the percent of patients that required an intervention.

The Variation in Plasma Cortisol Levels in Response to Anesthetic Induction with Etomidate or Ketamine in Children Undergoing Intracardiac Repair of Tetralogy of Fallot on Cardiopulmonary Bypass

Objective: To compare the effect of a single induction dose of etomidate or ketamine on plasma cortisol levels in children with Tetralogy of Fallot (TOF) undergoing intra-cardiac repair on cardiopulmonary bypass (CPB). Design: A prospective randomized trial. Setting: Cardiac center of a tertiary care hospital. Participants: Thirty children with TOF undergoing intra-cardiac repair on CPB. Interventions: After random allocation of the children into two groups, the children either received etomidate 0.2 mg/kg or ketamine 2 mg/kg intravenously for anesthetic induction along with fentanyl 2 mcg/kg and midazolam 100 mcg/kg. Endotracheal intubation was accomplished with rocuronium bromide in the dose of 1 mg/kg. Anesthesia was maintained with sevoflurane in air-oxygen, titrated to response and supplemental vecuronium bromide for muscle relaxation, fentanyl chloride for pain relief. Serum cortisol was measured on three occasions, at preinduction, at the end of surgery and at 24 hours postoperatively. Measurements and Main Results: Baseline plasma cortisol (Normal 5 - 25 mcg/dl) in the etomidate group (19.91 ± 3.51 mcg/dl) decreased significantly at the end of surgery (5.78 ± 2.0 mcg/dl) and rose to significantly higher than baseline values at 24 hours (27.31 ± 8.30 mcg/dl). The baseline cortisol levels in the ketamine group (20.91 ± 3.19 mcg/dl) increased significantly at the end of surgery (44.02 ± 5.49 mcg/dl) and remained significantly higher than baseline at 24hours (45.93 ± 3.05 mcg/dl). Plasma cortisol levels in the etomidate group at end of surgery, and at 24 hours post-operatively, were significantly lower than the ketamine group. Conclusions: This study shows that etomidate is a suitable and safe agent for suppression of the increase in serum cortisol associated with the use of CPB in children with TOF undergoing intra-cardiac repair.

The Effects of Etomidate and Propofol Induction on Hemodynamic and Endocrine Response in Patients Undergoing Coronary Artery Bypass Graft Surgery on Cardiopulmonary Bypass

Aim: To compare the effects of propofol and etomidate induction on hemodynamic parameters and serum cortisol levels in patients with normal left ventricular function undergoing elective coronary artery bypass graft surgery on cardiopulmonary bypass. Material and Method: After approval from the Institute Ethics committee hundred American Society of Anesthesiologists (ASA) grade II or III patients undergoing scheduled coronary artery bypass surgery on cardiopulmonary bypass were enrolled in the study. Patients were allocated randomly to receive either propofol or etomidate for anesthesia induction. Anesthesia was maintained in both groups with sevoflurane, vecuronium bromide for muscle relaxation (0.1 mg/kg, boluses) and fentanyl up to a total dose of 20 mcg/kg. Result: The baseline serum cortisol values were within normal limits in both the groups. The serum cortisol levels in the propofol group increased more than two fold, whereas the values in the etomidate group decreased by close to fifty percent on weaning from cardiopulmonary bypass (CPB). There was no significant difference in serum cortisol levels in the two groups at twenty-four hours after induction, although the values were close to double the baseline levels. Hemodynamically, etomidate group was more stable than propofol group following induction of anesthesia (P < 0.05). Conclusion: The surge in serum cortisol levels on the initiation of CPB seen after the use of propofol is prevented by the use of etomidate. Serum cortisol levels in both groups are well above the baseline at twenty-four hours without any untoward effects. Etomidate provides more stable hemodynamic parameters when used for induction of anesthesia as compared to propofol.

Effects of etomidate maintenance anesthesia on immunoglobulin and stress response levels in patients with gastric cancer after operation

Objective: To investigate the effect of etomidate maintenance anesthesia on immune function and stress response in patients with gastric cancer after the operation. Methods: 160 patients with gastric cancer in our hospital were randomly divided into control group and observation group, with 80 cases in each group. Both of the groups underwent radical gastrectomy, in which the control group was injected propofol anesthesia, while the observation group was injected etomidate anesthesia. The levels of immunoglobulin A, immunoglobulin M, immunoglobulin G, cortisol(Cor), aldosterone(ALD), malondialdehyde (MDA), superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), tumor necrosis factor-α (TNF-α) and hypersensitive C-reactive protein (hs-CRP) were detected and compared before and after treatment. Results: After treatment, the serum levels of immunoglobulin A, immunoglobulin G and immunoglobulin M of the patients in the control group were significantly decreased. But in the observation group, these serum level did not change significantly and were higher compared with the control group. The serum levels of Cor, ALD, SOD, and GSH-Px in both groups after treatment were significantly decreased, while the levels of MDA, TNF-α and hs-CRP were significantly increased. The serum levels of Cor, ALD, MDA, TNF-α, and hs-CRP of patients in the observation group were significantly lower than those in the control group, and the levels of SOD and GSH-Px were significantly higher than those in the control group. Conclusion: Etomidate can enhance the immune function and antioxidant capacity of patients with gastric cancer, alleviate inflammation, and has a good clinical effect. But it is not suitable for patients with severe impairment of adrenocortical function.

Effectof etomidate combined with propofol on stress and inflammatory response in painless gastrointestinal endoscopy

Objective: To study the effect of etomidate combined with propofol on stress and inflammatory response in painless gastrointestinal endoscopy. Methods: A total of 380 subjects who received painless gastrointestinal endoscopy in the hospital were selected as the research subjects and divided into control group and observation group by random number table, 190 cases in each group. Control group received propofol intravenous anesthesia, and observation group received etomidate combined with propofol intravenous anesthesia. The differences in serum levels of stress indexes and inflammatory factors were compared between the two groups 24 h before examination, during examination and 1 h after examination. Results: 24 h before examination, difference in serum levels of stress indexes and inflammatory factors were not statistically significant between the two groups of subjects. During examination and 1 h after examination, serum NE, E, Cor, ALD, AT-Ⅱ, IL-1β, IL-4, IL-6, IL-8, IL-10 and TNF-α contents of both groups were higher than those 24 h before examination, and serum NE, E, Cor, ALD, AT-Ⅱ, IL-1β, IL-4, IL-6, IL-8, IL-10 and TNF-α contents of observation group were lower than those of control group. Conclusion: Etomidate combined with propofol for painless gastrointestinal endoscopy can effectively alleviate the stress and inflammatory response during and early after the examination.

Effect of remifentanil combined with etomidate on systemic stress reaction during painless fiberoptic bronchoscopy

Objective:To study the effect of remifentanil combined with etomidate on systemic stress reaction during painless fiberoptic bronchoscopy.Methods:A total of 84 patients who received painless fiberoptic bronchoscopy in outpatient and ward of our hospital between May 2014 and October 2016 were selected as the research subjects and randomly divided into two groups, observation group of patients accepted remifentanil combined with etomidate anesthesia, control group of patients received surface anesthesia, and in various time periods of inspection (before, during and after inspection), serum was collected respectively to test stress indexes.Results:Before inspection, serum NE, E, ACTH, Cor, PRA, AT-II, ALD, CRP, TNF-α, IL-6 and MCP-1 contents were not significantly different between two groups of patients;during and after inspection, serum NE, E, ACTH, Cor, PRA, AT-II, ALD, CRP, TNF-α, IL-6 and MCP-1 contents of both groups of patients were significantly higher than those before inspection, and serum NE, E, ACTH, Cor, PRA, AT-II, ALD, CRP, TNF-α, IL-6 and MCP-1 contents of observation group were significantly lower than those of control group. Conclusion:Remifentanil combined with etomidate can significantly inhibit the activation of systemic stress reaction and the release of stress hormones during painless fiberoptic bronchoscopy.

Neonatal Propofol and Etomidate Exposure Enhance Inhibitory Synaptic Transmission in Hippocampal Cornus Ammonis 1 Pyramidal Neurons

Background：Propofol and etomidate are the most important intravenous general anesthetics in the current clinical use and that mediate gamma-aminobutyric acid＇s （GABAergic） synaptic transmission.However,their long-term effects on GABAergic synaptic transmission induced by neonatal propofol or etomidate exposure remain unclear.We investigated the long-term GABAergic neurotransmission alterations,following neonatal propofol and etomidate administration.Methods：Sprague-Dawley rat pups at postnatal days 4 6 were underwent 6-h-long propofol-induced or 5-h-long etomidate-induced anesthesia.We performed whole-cell patch-clamp recording from pyramidal cells in the cornus ammonis 1 area of acute hippocampal slices of postnatal 80-90 days.Spontaneous and miniature inhibitory GABAergic currents （spontaneous inhibitory postsynaptic currents [sIPSCs] and miniature inhibitory postsynaptic currents [mIPSCs]） and their kinetic characters were measured.The glutamatergic tonic effect on inhibitory transmission and the effect of bumetanide on neonatal propofol exposure were also examined.Results：Neonatal propofol exposure significantly increased the frequency of mIPSCs （from 1.87 ± 0.35 Hz to 3.43 ± 0.51 Hz,P 〈 0.05） and did not affect the amplitude of mIPSCs and sIPSCs.Both propofol and etomidate slowed the decay time of mIPSCs kinetics （168.39 ± 27.91 ms and 267.02 ± 100.08 ms vs.68.18 ± 12.43 ms;P 〈 0.05）.Bumetanide significantly blocked the frequency increase and reversed the kinetic alteration of mIPSCs induced by neonatal propofol exposure （3.01 ± 0.45 Hz and 94.30 ± 32.56 ms）.Conclusions：Neonatal propofol and etomidate exposure has long-term effects on inhibitory GABAergic transmission.Propofol might act at pre-and post-synaptic GABA receptor A （GABAA） receptors within GABAergic synapses and impairs the glutamatergic tonic input to GABAergic synapses;etomidate might act at the postsynaptic site.

Underlying Mechanisms of Memory Deficits Induced by Etomidate Anesthesia in Aged Rat Model： Critical Role of Immediate Early Genes

Background： Etomidate （R- 1 -[ 1 -ethylphenyl] imidazole-5-ethyl ester） is a widely used anesthetic drug that had been reported to contribute to cognitive deficits after general surgery. However, its underlying mechanisms have not been fully elucidated. In this study, we aimed to explore the neurohiological mechanisms of cognitive impairments that caused by etomidate. Methods： A total of 30 Sprague-Dawley rats were used and divided into two groups randomly to receive a single injection ofeiomidate or vehicle. Then, the rats＇ spatial memory ability and neuronal survival were evaluated using the Morris water maze test and Nissl staining, respectively. Furthermore, we analyzed levels of oxidative stress, as well as cyclic adenosine 3＇,5＇-monophosphate response element-binding （CREB） protein phosphorylation and immediate early gene （IEG, including Arc, c-fos, and Egrl） expression levels using Western blot analysis. Results： Compared with vehicle-treated rats, the etomidate-treated rats displayed impaired spatial learning （day 4：27.26 ± 5.33 s vs. 35.52 ± 3.88s, t 2.988, P 0.0068; day 5： 15.84±4.02svs.30.67±4.23s,t=3.013,P=0.0057;day6：9.47±2.35svs.25.66±4.16s,t=3.567, P = 0.0036） and menaory ability （crossing times： 4.40 ± 1.18 vs. 2.06 ± 0.80, t = 2.896, P 0.0072; duration： 34.00± 4.24 s vs. 18.07 ±4.79 s, t = 3.023, P= 0.0053; total swimming distance： 40.73 ±3.45 cm vs. 27.40± 6.56 cm, t = 2.798, P = 0.0086） but no neuronal death. Furthermore, etomidate did not cause oxidative stress or deficits in CREB phosphorylation. The levels of multiple lEGs （Arc： vehicle treated rats 100%, etomidate treated rats 86%, t = 2.876, P 0.0086; c-los： Vehicle treated rats 100%, etomidate treated rats 72%, t =2.996, P = 0.0076; Egrl ： Vehicle treated rats 100%, etomidate treated rats 58%, t = 3.011, P=0.0057） were significantly reduced in hippocampi ofetomidate-treated rats. Conclusion： Our data suggested that etomidate might induce memory impairment in rats via inhibition of lEG expression.

Effect of etomidate on voltage-dependent potassium currents in rat isolated hippocampal pyramidal neurons

Background Previous studies demonstrated general anesthetics affect potassium ion channels, which may be one of the mechanisms of general anesthesia. Because the effect of etomidate on potassium channels in rat hippocampus which is involved in memory function has not been studied, we investigated the effects of etomidate on both delayed rectifier potassium current （IK（DR）） and transient outward potassium current （I_K（A）） in acutely dissociated rat hippocampal pyramidal neurons.Methods Single rat hippocampal pyramidal neurons from male Wistar rats of 7-10 days were acutely dissociated by enzymatic digestion and mechanical dispersion according to the methods of Kay and Wong with slight modification. Voltage-clamp recordings were performed in the whole-cell patch clamp configuration. Currents were recorded with a List EPC-10 amplifier and data were stored in a computer using Pulse 8.5. Student＇s paired two-tail t test was used for data analysis. Results At the concentration of 100 μmol/L, etomidate significantly inhibited IK（DR） by 49.2% at ＋40 mV when depolarized from -110 mV （P 〈0.01, n=8）, while did not affect IK（A） （/1=8, P 〉0.05）. The IC50value of etomidate for blocking IK（DR）was calculated as 5.4 μmol/L, with a Hill slope of 2.45. At the presence of 10 μmol/L etomidate, the V1/2 of activation curve was shifted from （17.3±1.5） mV to （10.7±9.9） mV （n=8, P 〈0.05）, the V1/2 of inactivation curve was shifted from （-18.3±2.2） mV to （-45.3±9.4） mV （n=8, P 〈0.05）. Etomidate 10 μmol/L shifted both the activation curve and inactivation curve of IK（DR））to negative potential, but mainly affected the inactivation kinetics.Conclusions Etomidate potently inhibited IK（DR） but not IK（A） in rat hippocampal pyramidal neurons. IK（DR） was inhibited by etomidate in a concentration-dependent manner, while IK（A） remained unaffected.

Study on Acupuncture for Side Effects of Etomidate Anesthesia

Objective: To evaluate the effect of acupuncture therapy on the side effect of Etomidate anesthesia and to determine the best timing of acupuncture intervention during Etomidate anesthesia. Methods: Female patients with rectal cancer scheduled to receive radical resection were randomly divided into four groups: a control group(group Ⅰ), a preoperative acupuncture group(group Ⅱ), an intraoperative acupuncture group(group Ⅲ), and a postoperative acupuncture group(group Ⅳ), 25 subjects in each group. The levels of serum cortisol, blood glucose, and gastrin of patients were monitored at the following time-points: preoperative(T0, when having entered the operating room), intraoperative(T1, 30 min after skin cutting), the end of operation(T2, after suturing skin), and postoperative(T3, postoperative 24 h). The cases with massive hemorrhage, unsteady vital sign during operation or operation time longer than 5 h were eliminated, and 92 cases were enrolled into the results of the study. Results: The blood sugar in the four groups increased significantly at T2 and T3, compared to T0(P < 0.05); the blood sugar reached((.(((1.5() mmol(( at T2 in group Ⅲ, and the increase was statistically significant compared to those of the other groups(P<0.05). The levels of serum cortisol of all patients were in normal range. Compare to T0, the cortisol level decreased in group Ⅰ, Ⅲ, at each point, and the decreases Ⅳ were statistically significant(P<0.05). Compared to the other groups, the cortisol level was increased at T1 and T3 in group Ⅱ, and the change was statistically significant(P<0.05). Compared to T0, the gastrin level at T3 increased in group Ⅰ, Ⅲand Ⅳ, but decreased in group Ⅱ, and the changes had statistical significance(P<0.05). Compared to the other groups, the decrease of gastrin level in group Ⅱat T3 was statistically significant(P<0.05). Conclusion: Acupuncture before operation can keep blood sugar and serum cortisol steady during Etomidate anesthesia and reduce gastrin after Etomidate anesthesia, hence regulating the Etomidate-related stress responses effectively.

Impact of the United States propofol ban on emergency providers' procedural sedation agent choice and patient length of stay

In the recent past, propofol was temporarily removed from the emergency department （ED） for use in procedural sedation. We sought to determine which agents replaced it in clinical practice and the impact this change had on turnaround times （TAT） for sedated patients. This study is a retrospective chart review at a level one trauma center. Patients receiving sedative agents （propofol, ketamine, midazolam, and etomidate） were identified by pharmacy codes, and their charts were then reviewed for demographics and TAT. Propofol was unavailable in the emergency department （ED） between May 2010 and February 2011. The study period extended from May 2009 until May 2011. Patients receiving sedation by non-emergency medicine physicians and those receiving sedation related to intubation were excluded. In total 2466 charts were reviewed and 209 met inclusion criteria. When propofol was available, the most commonly used sedative agent was etomidate （40%）, followed by propofol （28%）, ketamine （20%）, and midazolam （6%）. When propofol was unavailable, etomidate remained the most commonly used agent （43%）, followed by ketamine （41%）, and midazolam （11%）. When propofol was available, the median TAT for sedated patients was 163 minutes compared to 178 minutes when propofol was unavailable （P=0.83）. When propofol was the primary sedative agent used, the median TAT was 166 minutes as compared with a median TAT of 172 minutes for all other sedative agents combined （P=0.87）. When propofol was unavailable, ketamine became a preferred ED sedation agent. Removal of propofol from the sedation armamentarium did not affect ED TAT.