The primary intravenous anesthetics employed in clinical practice encompass dexmedetomidine (Dex), propofol, ketamine, etomidate, midazolam, and remimazolam. Apart from their established sedative, analgesic, and anxiolytic properties, an increasing body of research has uncovered neuroprotective effects of intravenous anesthetics in various animal and cellular models, as well as in clinical studies. However, there also exists conflicting evidence pointing to the potential neurotoxic effects of these intravenous anesthetics. The role of intravenous anesthetics for neuro on both sides of protection or toxicity has been rarely summarized. Considering the mentioned above, this work aims to offer a comprehensive understanding of the underlying mechanisms involved both in the central nerve system (CNS) and the peripheral nerve system (PNS) and provide valuable insights into the potential safety and risk associated with the clinical use of intravenous anesthetics.
Animals ; Humans ; Anesthetics, Intravenous/adverse effects* ; Neuroprotective Agents/pharmacology* ; Propofol ; Neurotoxicity Syndromes/prevention & control* ; Central Nervous System/drug effects* ; Dexmedetomidine

Clinical researches including the Mayo Anesthesia Safety in Kids (MASK) study have found that children undergoing multiple anesthesia may have a higher risk of fine motor control difficulties. However, the underlying mechanisms remain elusive. Here, we report that erythropoietin receptor (EPOR), a microglial receptor associated with phagocytic activity, was significantly downregulated in the medial prefrontal cortex of young mice after multiple sevoflurane anesthesia exposure. Importantly, we found that the inhibited erythropoietin (EPO)/EPOR signaling axis led to microglial polarization, excessive excitatory synaptic pruning, and abnormal fine motor control skills in mice with multiple anesthesia exposure, and those above-mentioned situations were fully reversed by supplementing EPO-derived peptide ARA290 by intraperitoneal injection. Together, the microglial EPOR was identified as a key mediator regulating early synaptic development in this study, which impacted sevoflurane-induced fine motor dysfunction. Moreover, ARA290 might serve as a new treatment against neurotoxicity induced by general anesthesia in clinical practice by targeting the EPO/EPOR signaling pathway.
Animals ; Sevoflurane/toxicity* ; Microglia/drug effects* ; Anesthetics, Inhalation/adverse effects* ; Mice ; Mice, Inbred C57BL ; Receptors, Erythropoietin/metabolism* ; Neuronal Plasticity/drug effects* ; Male ; Prefrontal Cortex/drug effects* ; Erythropoietin/pharmacology* ; Signal Transduction/drug effects*

OBJECTIVE: To explore if acupoint injection can improve analgesic effects or delivery outcomes in parturients who received combined spinal-epidural analgesia (CSEA) and patient-controlled epidural analgesia (PCEA) for labor analgesia. METHODS: A total of 307 participants were prospectively collected from July 2017 to December 2019. The participants were randomized into the combined acupoint injection with CSEA plus PCEA group (AICP group, n=168) and CSEA plus PCEA group (CP group, n=139) for labor analgesia using a random number table. Both groups received CSEA plus PCEA at cervical dilation 3 cm during labor process, and parturients of the AICP group were implemented acupoint injection for which bilateral acupoint of Zusanli (ST 36) and Sanyinjiao (SP 6) were selected in addition. The primary outcome was Visual Analogue Scale (VAS) score, and the secondary outcomes were obstetric outcomes and requirement of anesthetics doses. Safety evaluations were performed after intervention. RESULTS: The VAS scores were significantly lower in the AICP group than in the CP group at 10, 30, 60, and 120 min after labor analgesia (all P<0.05). The latent phase of the AICP group was shorter than that of the CP group (P<0.05). There were less additional anesthetics consumption, lower incidences of uterine atony, fever, pruritus and urinary retention in the AICP group than those in the CP group (all P<0.05). CONCLUSION Acupoint injection combined CSEA plus PCEA for labor analgesia can decrease the anesthetic consumption, improve analgesic quality, and reduce adverse reactions in the parturients. (Registration No. ChiMCTR-2000003120).
Acupuncture Points ; Analgesia, Obstetrical/adverse effects* ; Analgesia, Patient-Controlled/adverse effects* ; Anesthetics/pharmacology* ; Female ; Humans ; Labor, Obstetric ; Pregnancy

OBJECTIVEAnesthetic isoflurane plus surgery has been reported to induce cognitive impairment. The underlying mechanism and targeted intervention remain largely to be determined. Ginsenoside Rb1 was reported to be neuroprotective. We therefore set out to determine whether ginsenoside Rb1 can attenuate isoflurane/surgery-induced cognitive dysfunction via inhibiting neuroinflammation and oxidative stress.

METHODSFive-months-old C57BL/6J female mice were treated with 1.4% isoflurane plus abdominal surgery for two hours. Sixty mg/kg ginsenoside Rb1 were given intraperitoneally from 7 days before surgery. Cognition of the mice were assessed by Barnes Maze. Levels of postsynaptic density-95 and synaptophysin in mice hippocampus were measured by Western blot. Levels of reactive oxygen species, tumor necrosis factor-α and interleukin-6 in mice hippocampus were measured by ELISA.

RESULTSHere we show for the first time that the ginsenoside Rb1 treatment attenuated the isoflurane/surgery-induced cognitive impairment. Moreover, ginsenoside Rb1 attenuated the isoflurane/surgery-induced synapse dysfunction. Finally, ginsenoside Rb1 mitigated the isoflurane/surgery-induced elevation levels of reactive oxygen species, tumor necrosis factor-α and interleukin-6 in the mice hippocampus.

CONCLUSIONThese results suggest that ginsenoside Rb1 may attenuate the isoflurane/surgery-induced cognitive impairment by inhibiting neuroinflammation and oxidative stress pending future studies.

Anesthetics, Inhalation ; adverse effects ; Animals ; Cognition ; Cognitive Dysfunction ; etiology ; prevention & control ; Female ; Ginsenosides ; pharmacology ; Hippocampus ; drug effects ; Inflammation ; etiology ; prevention & control ; Isoflurane ; adverse effects ; Medicine, Chinese Traditional ; Mice ; Mice, Inbred C57BL ; Oxidative Stress ; Postoperative Complications ; etiology ; prevention & control ; Random Allocation ; Surgical Procedures, Operative ; adverse effects ; Synapses ; metabolism

PURPOSE: This study aims to investigate the most appropriate effect-site concentration of remifentanil to minimize cardiovascular changes during inhalation of high concentration desflurane. MATERIALS AND METHODS: Sixty-nine American Society of Anesthesiologists physical status class I patients aged 20-65 years were randomly allocated into one of three groups. Anesthesia was induced with etomidate and rocuronium. Remifentanil was infused at effect-site concentrations of 2, 4 and 6 ng/mL in groups R2, R4 and R6, respectively. After target concentrations of remifentanil were reached, desflurane was inhaled to maintain the end-tidal concentration of 1.7 minimum alveolar concentrations for 5 minutes (over-pressure paradigm). The systolic blood pressure (SBP), diastolic blood pressure (DBP), mean arterial pressure (MAP), heart rate (HR) and end-tidal concentration of desflurane were measured for 5 minutes. RESULTS: The end-tidal concentration of desflurane increased similarly in all groups. The SBP, DBP, MAP and HR within group R4 were not significantly different as compared with baseline values. However, measured parameters within group R2 increased significantly 1-3 minutes after desflurane inhalation. The MAP within group R6 decreased significantly at 1, 2, 4, and 5 minutes (p<0.05). There were significant differences in SBP, DBP, MAP and HR among the three groups 1-3 minutes after inhalation (p<0.05). The incidence of side effects such as hyper- or hypo-tension, and tachy- or brady-cardia in group R4 was 4.8% compared with 21.8% in group R2 and 15.0% in group R6. CONCLUSION: The most appropriate effect-site concentration of remifentanil for blunting hemodynamic responses by inhalation of high concentration desflurane is 4 ng/mL.
Adult ; Aged ; Androstanols/adverse effects/pharmacology ; Anesthetics/adverse effects/pharmacology ; Anesthetics, Inhalation/adverse effects/*pharmacology ; Blood Pressure/drug effects ; Etomidate/adverse effects/pharmacology ; Female ; Heart/*drug effects ; Heart Rate/drug effects ; Humans ; Isoflurane/adverse effects/*analogs & derivatives/pharmacology ; Male ; Middle Aged ; Piperidines/adverse effects/*therapeutic use ; Protective Agents/adverse effects/*therapeutic use

PURPOSE: Opioids may affect changes in the corrected QT interval (QTc) during anesthetic induction. This study examine whether a single bolus of remifentanil would prolong QTc after laryngeal mask airway (LMA) insertion during sevoflurane induction. MATERIALS AND METHODS: Forty women of American Society of Anesthesiologists physical status 1 (ASA PS1) undergoing gynecological surgery were studied. All patients were induced using three vital capacity inhalation inductions with 5% sevoflurane. Two minutes after induction, the inspiratory concentration of sevoflurane was reduced to 2%. Using double-blinded randomization, patients were allocated into one of two groups, receiving either saline (placebo group, n = 20) or 0.25 microg.kg-1 remifentanil (remifentanil group, n = 20) over a period of thirty seconds. Sixty seconds later, LMA insertion was performed. Recordings were taken with a 12-lead electrocardiogram at baseline, 2 min after induction and 1 and 3 min after LMA insertion. QTc was calculated by Bazett's formula. The mean arterial pressure (MAP) and heart rate (HR) were also measured at each time point. RESULTS: The QTc interval was significantly prolonged in the placebo group as compared to the remifentanil group at 1 min after LMA insertion (467.8 +/- 16.5 vs. 442.7 +/- 21.3 ms, p < 0.001). However, there was no significant difference in QTc at 3 min after LMA insertion between the two groups. MAP and HR were significantly higher in the placebo group (p < 0.001). CONCLUSION: A single bolus of remifentanil is safe method to attenuate prolonged QTc associated with insertion of LMA.
Adult ; Anesthetics, Inhalation/adverse effects/*pharmacology ; Anesthetics, Intravenous/administration & dosage/*pharmacology ; Electrocardiography/drug effects ; Female ; Gynecologic Surgical Procedures/adverse effects ; Heart Rate/*drug effects ; Humans ; Methyl Ethers/adverse effects/*pharmacology ; Middle Aged ; Piperidines/*pharmacology

BACKGROUNDThe authors found no study to compare the efficacy of bolus dose fentanyl and remifentanil blunting the cardiovascular intubation response in children, so they designed this randomized, double-blind clinical study to assess the effects of remifentanil 2 microg/kg and fentanyl 2 microg/kg by bolus injection on the cardiovascular intubation response in healthy children.

METHODSOne hundred and two children, the American Society of Anesthesiologists (ASA) physical status 1-2 and scheduled for elective plastic surgery under general anesthesia, were randomly divided into one of two groups to receive the following treatments in a double blind manner: remifentanil 2 microg/kg (Group R) and fentanyl 2 microg/kg (Group F) when anesthesia was induced with propofol and vecuronium. The orotracheal intubation was performed using a direct laryngoscope. Blood pressure (BP) and heart rate (HR) were recorded before anesthesia induction (baseline values), immediately before intubation, at intubation and every minute for 5 minutes after intubation. The percent changes of systolic blood pressure (SBP) and HR relative to baseline values and the rate pressure product (RPP) at every observing point were calculated. The incidences of SBP and HR percent changes >30% of baseline values and RPP >22,000 during the observation were recorded.

RESULTSThere were no significant differences between groups in the demographic data, baseline values of BP and HR and the intubation time. As compared to baseline values, BP, HR and RPP at intubation and their maximum values during observation increased significantly in Group F, but they all decreased significantly in Group R. BP, HR and RPP at all observed points, and their maximum values during the observation, were significantly different between groups. There were also significant differences between groups in the percent change of SBP and HR relative to baseline values at all observed points and their maximum percent changes during the observation. The incidences of SBP and HR percent increased >30% of the baseline values and RPP >22,000 during the observation, were significantly higher in Group F than in Group R, but the incidences of SBP and HR percent decreased >30% of baseline values were significantly lower in Group F compared with Group R.

CONCLUSIONSWhen used as part of routine anesthesia induction with propofol and vecuronium in children, fentanyl 2 microg/kg by bolus injection fails to effectively depress the cardiovascular intubation response. Remifentanil 2 microg/kg by bolus injection can completely abolish the cardiovascular intubation response, but also cause more adverse complications of temporary significant cardiovascular depression.

Anesthetics, Intravenous ; pharmacology ; therapeutic use ; Blood Pressure ; drug effects ; Child ; Child, Preschool ; Double-Blind Method ; Female ; Fentanyl ; pharmacology ; therapeutic use ; Heart Rate ; drug effects ; Humans ; Intubation, Intratracheal ; adverse effects ; Male ; Piperidines ; pharmacology ; therapeutic use

OBJECTIVETo study the psychedelic effects in healthy volunteers when given subanesthetic dose of ketamine.

METHODSThirteen male healthy volunteers aged 24-39 years were enrolled. All subjects received subanesthetic doses of ketamine using target control infusion. A stepwise series of target plasma concentrations (0, 100, 200, and 300 ng/ml) were maintained for 20 minutes each. Visual analogue scale (VAS) of mechanical pain by von Frey hair was evaluated, and then the volunteers completed a VAS rating of 13 symptom scales. Pictures were shown to them at the same time. Heart rate, mean blood pressure, and SpO2 were monitored throughout the infusion.

RESULTSDuring the process of analgesia, ketamine produced dose-related analgesic effects. With the increase of ketamine dose, some psychedelic effects became more obvious and the memory impairment became worse stepwisely.

CONCLUSIONTarget control infusion of subanesthetic doses of ketamine produce obvious psychedelic effects in healthy volunteers.

Adult ; Anesthetics, Dissociative ; administration & dosage ; adverse effects ; pharmacology ; Dose-Response Relationship, Drug ; Hallucinations ; chemically induced ; Humans ; Ketamine ; administration & dosage ; adverse effects ; pharmacology ; Male

The purpose of this study was to determine the effectiveness of antihistamine therapy for withdrawal movements caused by rocuronium injection. One hundred seventy one ASA I-II adults undergoing elective surgery were randomly assigned to one of two groups. Patients in the control group (Group C) were premedicated with 2 mL normal saline, and those in the antihistamine group (Group A) were pre-medicated with 2 mL (45.5 mg) pheniramine maleate. After the administration of thiopental sodium 5 mg/kg, rocuronium 0.6 mg/kg was injected. Withdrawal movements were assessed using a four-grade scale. The administration of antihistamine reveals lower grade of withdrawal movement after rocuronium injection.
Adult ; Androstanols/*administration & dosage/adverse effects ; Anesthetics, Intravenous/administration & dosage ; Double-Blind Method ; Female ; Histamine H1 Antagonists/*pharmacology ; Humans ; Incidence ; Injections, Intravenous ; Male ; Middle Aged ; Movement/drug effects/physiology ; Neuromuscular Nondepolarizing Agents/*administration & dosage/adverse effects ; Pain/chemically induced ; Pain Measurement ; Pheniramine/*pharmacology ; Thiopental/administration & dosage

It was previously reported that the Korean predictive model could be used to identify patients at high risk of postoperative nausea and vomiting (PONV). This study investigated whether PONV in the high-risk and very high-risk patients identified by the Korean predictive model could be prevented by multiple prophylactic antiemetics. A total of 2,456 patients were selected from our previous PONV study and assigned to the control group, and 374 new patients were recruited consecutively to the treatment group. Patients in each group were subdivided into two risk groups according to the Korean predictive model: high-risk group and very high-risk group. Patients in the treatment group received an antiemetic combination of dexamethasone 5 mg (minutes after induction) and ondansetron 4 mg (30 min before the end of surgery). The incidences of PONV were examined at two hours after the surgery in the postanesthetic care unit and, additionally, at 24 hr after the surgery in the ward, and were analyzed for any differences between the control and treatment groups. The overall incidence of PONV decreased significantly from 52.1% to 23.0% (p< or =0.001) after antiemetic prophylaxis. Specifically, the incidence decreased from 47.3% to 19.4% (p< or =0.001) in the high-risk group and from 61.3% to 28.3% (p< or =0.001) in the very high-risk group. Both groups showed a similar degree of relative risk reductions: 59.0% vs. 53.8% in the high-risk and very high-risk groups, respectively. The results of our study showed that the antiemetic prophylaxis with the combination of dexamethasone and ondansetron was effective in reducing the occurrence of PONV in both high-risk and very high-risk patients.
Adult ; Anesthetics/adverse effects ; Antiemetics/*pharmacology ; Dexamethasone/administration & dosage ; Female ; Humans ; Incidence ; Korea ; Middle Aged ; Ondansetron/administration & dosage ; Postoperative Complications/prevention & control ; Postoperative Nausea and Vomiting/*prevention & control ; Postoperative Period ; Risk ; Risk Factors ; Treatment Outcome