Evaluating efficacy and safety of sub-anesthetic dose esketamine as an adjuvant to propofol/remifentanil analgosedation and spontaneous respiration for children flexible fibreoptic bronchoscopy: a prospective, double-blinded, randomized, and placebo-controlled clinical trial.

Background: Flexible fiberoptic bronchoscopy (FFB) for children is widely performed under sedation. Currently, the optimal sedation regimen remains unclear. Esketamine is an N-methyl-D-aspartic acid (NMDA) receptor antagonist, which has stronger sedative and analgesic effects and exerts less cardiorespiratory depression than other sedatives. The purpose of this study was to evaluate whether a subanesthetic dose of esketamine as an adjuvant to propofol/remifentanil and spontaneous ventilation compared with control reduces the procedural and anesthesia-related complications of FFB in children. Materials and methods: Seventy-two children ≤ 12 years of age who were scheduled for FFB were randomly assigned, in a 1:1 ratio, to the esketamine-propofol/remifentanil (Group S, n = 36) or to the propofol/remifentanil group (Group C, n = 36). All children were retained spontaneous ventilation. The primary outcome was the incidence of oxygen desaturation (respiratory depression). Perioperative hemodynamic variables, blood oxygen saturation (SPO2), end-tidal partial pressure of carbon dioxide (PetCO2), respiratory rate (R), and the Bispectral index (BIS), induction time, procedural time, recovery time, the time to the ward from the recovery room, consumption of propofol and remifentanil during the procedure and the appearance of adverse events, including paradoxical agitation following midazolam administration, injection pain, laryngospasm, bronchospasm, PONV, vertigo, and hallucination were also compared. Results: The incidence of oxygen desaturation was significantly lower in Group S (8.3%) compared to Group C (36.1%, p = 0.005). The perioperative hemodynamic profile including SBP, DBP, and HR were more stable in Group S than that in Group C (p < 0.05). Consumption of propofol and remifentanil was lower in Group S than in Group C (p < 0.05). Furthermore, PAED scores, cough scores and injection pain were lower in the Group S than in Group C (p < 0.05). The recovery time of Group S was slightly longer than that of Group C (p < 0.05). Nobody happened paradoxical agitation following midazolam administration, PONV, vertigo, and hallucinations in both groups (p > 0.05). Conclusion: Our findings indicate that a subanesthetic dose of esketamine as an adjuvant to propofol/remifentanil and spontaneous respiration is an effective regimen for children undergoing FFB. Our findings will provide a reference for clinical sedation practice during these procedures in children. Clinical Trail Registration: Chinese clinicaltrials.gov registry (identifier: ChiCTR2100053302).

Effect of a single sub-dose of ketamine on postoperative fatigue syndrome in colorectal cancer patients undergoing radical laparoscopic surgery: A double-blind, pilot study.

BACKGROUND: This study aimed at examining the effect of a single sub-anesthetic dose of ketamine on postoperative fatigue syndrome (POFS) in patients undergoing radical laparoscopic surgery for colorectal cancer (CRC). METHODS: This prospective, double-blind, pilot study enrolled patients scheduled for radical laparoscopic surgery for CRC under general anesthesia. Eligible patients were randomized into the placebo and ketamine groups. The primary outcome was christensen score change at day 3. The secondary outcomes were the difference of Identity Consequence Fatigue Scale (ICFS) score between the placebo group and ketamine group at day 3 and level of serum tumor necrosis factor (TNF)-α, interleukin (IL)-6, S100ß protein, and neuron-specific enolase (NSE). RESULTS: 32 participants were assigned to the ketamine group and 31 to the placebo group. Compared with placebo group, the Christensen score was lower in ketamine group at day 3 (absolute difference, -1.13; 95 % confidence interval [CI], -2.02 to -0.24; P = 0.012). Ketamine group was superior to the placebo group with regard to the ICFS scores at day 3 (absolute difference, -6.4; 95 % CI, -11.4 to -1.4; P = 0.013). The plasma TNF-α, IL-6, S100ß, and NSE levels were increased after operation compared with baseline in both groups and were significantly higher in placebo group than in ketamine group within 24 h after surgery (all P < 0.05). There was no significant difference of each safety evaluation indicator between the two groups (all P > 0.05). CONCLUSION: A single sub-anesthetic dose of ketamine may improve POFS in patients undergoing radical laparoscopic surgery for CRC, without postoperative adverse reactions.

Effects of a Single Sub-Anesthetic Dose of Ketamine on Postoperative Emotional Responses and Inflammatory Factors in Colorectal Cancer Patients.

Objective: To investigate the effect of a single sub-anesthetic dose of ketamine on postoperative anxiety, depression, and inflammatory factors in patients with colorectal cancer. Methods: A total of 104 patients undergoing selective colorectal surgery in our hospital from Jan 2015 to Oct 2017 were included and randomly assigned (1:1:1:1) into a 0.1 mg kg-1 ketamine group (K1 group), 0.2 mg kg-1 ketamine group (K2 group), 0.3 mg kg-1 ketamine group (K3 group), or control group (C group). Corresponding doses of ketamine were given intravenously in the K groups (K1, K2, and K3 groups) 5 min before operation, and the same amount of normal saline was given in the C group. The intravenous analgesia program was identical in the four groups. The patients' emotional reactions (anxiety and depression) were assessed by the Hospital Anxiety and Depression Scale (HAD), the quality of postoperative recovery was evaluated by the Quality of Recovery-40 (QoR-40) questionnaire, and the levels of IL-6, IL-8, and TNF-α in peripheral blood were detected by enzyme-linked immunosorbent assay (ELISA) on the day before operation and within 24, 48, and 72 h post-operation respectively. Pain was estimated by the visual analog scale (VAS), and sedation was assessed with Ramsay score 30 min after extubation. The time points of anesthetic end and extubation were recorded. The complications during anesthesia and recovery such as cough and agitation 30 min after extubation were recorded. Results: The anxiety score (HAD-A) and depression score (HAD-D) of the K3 group were significantly lower than those of the C group post-operation (p < 0.05). The QoR-40 score of the K3 group was significantly higher than that of the C group (p < 0.05). The serum levels of IL-6, IL-8, and TNF-α in the K3 group were significantly lower than those in the C group (p < 0.05 and p < 0.01). There were no significant differences in HAD-A, HAD-D, and QoR-40 scores or serum levels of IL-6, IL-8, and TNF-α between the K1 and K2 groups and the C group. There were no significant differences in VAS pain score or Ramsay sedation score among the four groups 30 min after extubation. There were no significant differences in extubation time, postoperative cough, emergence agitation, or delirium among the four groups. Dizziness, nausea, vomiting, diplopia, or other adverse reactions were not found 30 min after extubation. Conclusion: A single sub-anesthetic dose (0.3 mg kg-1) of ketamine can significantly improve the postoperative anxiety and depression of colorectal cancer patients and reduce the levels of IL-6, IL-8, and TNF-α.

Comparing the minimum local anesthetic dose of ropivacaine in real-time ultrasound-guided spinal anesthesia and traditional landmark-guided spinal anesthesia: a randomized controlled trial of knee surgery patients.

BACKGROUND: Through previous studies and clinical practice, we have found that real-time ultrasound-guided (UG) spinal anesthesia (SA) and traditional landmark-guided (LG) SA each require a different minimum local anesthetic dose (MLAD) of ropivacaine. For this study, we used Dixon's up-and-down sequential method to analyze and compare the MLAD of different ropivacaine concentrations required for the UG and LG SA methods. METHODS: A total of 120 patients undergoing knee surgery were consecutively recruited and randomly divided into four groups (30 patients per group). These groups were categorized as follows: Group I: high ropivacaine ultrasound-guided (HRUG), Group II: low ropivacaine ultrasound-guided (LRUG), Group III: high ropivacaine landmark-guided (HRLG), and Group IV: low ropivacaine landmark-guided (LRLG). SA was established by a bolus administration of up-and-down doses of 0.75% or 0.5% plain ropivacaine. Initial doses of 16, 18, 12, and 14 mg were administered to groups I-IV, and after that, increased or decreased by 1.5 mg according to dose effectiveness. Upon identifying the intervertebral puncture level, a lumbar X-ray was performed with metal markers, and actual radiographic findings were identified and compared to the initial markings. RESULTS: For UG groups, the MLAD in the LRUG group was significantly higher than in the HRUG group [20.192 mg (95% CI, 19.256-21.174) versus 17.176 mg (95% CI, 16.276-18.124), respectively; P<0.001]. For LG groups, the MLAD in the LRLG group was significantly higher than in the HLRG group [14.478 mg (95% CI, 13.364-15.500) versus 13.201 mg (95% CI, 11.959-14.571), respectively; P=0.047]. When comparing both high ropivacaine groups (HRGs: I/III) to the low ropivacaine groups (LRGs: II/IV), we found that both UG subgroups (I/II) had a significantly higher MLAD than LG subgroups (III/IV) (P<0.001). US identified L4-5 in up to 90% of cases. Comparatively, palpation was successful in only 33.3% of patients. The rates of cephalad localization by US and palpation were 6.67% vs. 66.67%, respectively (P=0.002). CONCLUSIONS: We found a higher MLAD of ropivacaine was required for UG SA at the L4-5 level due to the method providing a more accurate (less cephalad) localization than traditional LG SA. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR2000033158.

Sedative Effects of Intramuscular Dexmedetomidine and Ketamine at Sub-Anesthetic Dose Alone or in Combination with Methadone in Healthy Dogs.

The aim of the present study was to compare sedation quality and cardiorespiratory parameters in healthy dogs after intramuscular injection of dexmedetomidine and ketamine with or without methadone. Forty client-owned dogs were randomly divided into two groups and received IM dexmedetomidine (5 µg kg-1) and ketamine (1 mg kg-1), associated (DKM group) or not (DK group) with methadone (0.2 mg kg-1). Sedation, heart rate (HR), respiratory rate (ƒR), mucous membrane and rectal temperature were recorded at baseline (T0) and after 5 (T5), 10 (T10) and 20 (T20) minutes. From T10, cardiac rhythm was monitored with a continuous lead II electrocardiogram. Ease of venous catheter placement, total propofol dose and any apnea episodes were recorded. Sedation was significantly greater in the DKM group, and a significant increase from T5 to T20 within DKM (P = .0002) and DK (P = .008) was also observed. Within each group, HR was significantly lower at all time points compared to baseline. No significant differences between groups were found in the number of arrhythmogenic events (atrioventricular blocks). In both group ƒR decreased over time. The propofol dose required for anesthesia induction was significantly lower (P = .027) in the DKM group. In conclusion, a good level of sedation was achieved in both groups, although this was greater in DKM. Smooth animal-operator interaction and ease of venous catheter placement showed that DK was a useful sedative protocol in healthy patients.

Sub-anesthetic and anesthetic ketamine produce different long-lasting behavioral phenotypes (24 h post-treatment) via inducing different brain-derived neurotrophic factor (BDNF) expression level in the hippocampus.

Clinical and preclinical researches have shown that sub-anesthetic ketamine elicits sustained antidepressant effects for up to 1-2 weeks. Pharmacokinetics studies (t1/2 = 23 min) in mice showed no ketamine residue at 24 h after sub-anesthetic or anesthetic ketamine administration. Therefore, this study aims to reveal the mechanism underlying these different biological functions at 24 h after sub-anesthetic and anesthetic ketamine treatment. First, at the animal behavioral level, we found that sub-anesthetic ketamine induced antidepressant and anxiolytic effects while anesthetic ketamine induced depressive-like phenotypes and cognitive impairment. Second, we examined the correlation between behavior phenotype and protein expression, and found that the Brain-derived neurotrophic factor (BDNF) level is oppositely regulated by sub-anesthetic and anesthetic ketamine. Sub-anesthetic ketamine significantly increased the BDNF level, correlating to antidepressant effects; whereas anesthetic dose reduced BDNF expression in the hippocampus, correlating to depressive-like behaviors, anxiety-like behaviors and cognitive impairment. Third, the antidepressant effects of sub-anesthetic ketamine were prevented by pre-treatment of ANA-12, a Tropomyosin receptor kinase B (TrkB) inhibitor. Thus, we conclude that BDNF may be the key factor underlying antidepressant and anxiolytic effects of sub-anesthetic ketamine at 24 h after treatment. These results may shed light on future studies and the development of long-lasting anti-depressant drugs and therapies.

The effect of anesthetic dose on the motor response induced by low-intensity pulsed ultrasound stimulation.

BACKGROUND: Low-intensity pulsed ultrasound stimulation (LIPUS) has been proven to be a noninvasive method with high spatial resolution and deep penetration. Previous studies have qualitatively demonstrated that the electromyographic response caused by LIPUS in the mouse motor cortex is affected by the anesthetic state of the mice. However, the quantitative relationship between motor response and anesthetic dose remains unclear. RESULTS: Experimental results show that the success rate decreases stepwise as the isoflurane concentration/mouse weight ratio increases (ratios: [0.004%/g, 0.01%/g], success rate: ~ 90%; [0.012%/g, 0.014%/g], ~ 40%; [0.016%/g, 0.018%/g], ~ 7%; 0.024%/g, 0). The latency and duration of EMG increase significantly when the ratio is more than 0.016%/g. Compared with that at ratios from 0.004 to 0.016%/g, normalized EMG amplitude decreases significantly at ratios of 0.018%/g and 0.020%/g. CONCLUSIONS: Quantitative calculations indicate that the anesthetic dose has a significant regulatory effect on the motor response of mice during LIPUS. Our results have guiding significance for the selection of the anesthetic dose for LIPUS in mouse motor cortex experiments.

Effect of a single sub-anesthetic dose of ketamine on emotion of patients with colorectal cancer during early period of postoperation / 临床麻醉学杂志

Objective To investigate the impact of a single sub-anesthetic dose of ketamine on postoperative emotional reactions of anxiety and depression during colorectal tumors surgery. Methods A total of 42 patients undergoing selective colorectal surgery,aged 18 to 65 years,were randomly divided into ketamine group (group K)and control group (group C).After induction of an-esthesia,a single intravenous injection of 0.3 mg/kg ketamine and saline were used in Group K and group C 5 minutes before the operation respectively.The intravenous analgesia program was identical between the two groups.The patients??emotional reactions (anxiety,depression)were assessed using the Hospital Anxiety and Depression Scale (HAD),the quality of recovery was assessed using the QoR-40 questionnaire on the day before operation and within postoperative 48 hours respectively.Pain was estimated by the visual analog scale (VAS)and sedation was assessed with Ramsay score 30 mi-nutes after extubation.The time of anesthetic end and extubation were recorded.The complications during anesthesia and recovery such as cough, agitation 30 minutes extubation were recorded. Results The HAD-A and HAD-D scores of group K were lower than group C (P <0.05)48 h post-operatively.There was no difference on the QoR-40 score postoperative 48 h between the two groups. The patients??emotional state QoR-40 score of group K were higher than group C (P <0.05 ).The VAS scores 30 minutes after extubation of group K were lower than group C (P <0.05).There was no significant difference on sedation score 30 minutes postoperatively between the two groups.There was no significant difference in extubation time,cough,agitation and delirium between the two groups.There was no dizziness, nausea, vomiting or diplopia 30 minutes after extubation. Conclusion A single subanesthetic dose of ketamine can significantly reduce the scores of postopera-tive anxiety and depression,improve the quality of recovery,and no postoperative adverse reactions increased.

Deep sedation during gastrointestinal endoscopy: propofol-fentanyl and midazolam-fentanyl regimens.

AIM: To compare deep sedation with propofol-fentanyl and midazolam-fentanyl regimens during upper gastrointestinal endoscopy. METHODS: After obtaining approval of the research ethics committee and informed consent, 200 patients were evaluated and referred for upper gastrointestinal endoscopy. Patients were randomized to receive propofol-fentanyl or midazolam-fentanyl (n = 100/group). We assessed the level of sedation using the observer's assessment of alertness/sedation (OAA/S) score and bispectral index (BIS). We evaluated patient and physician satisfaction, as well as the recovery time and complication rates. The statistical analysis was performed using SPSS statistical software and included the Mann-Whitney test, χ² test, measurement of analysis of variance, and the κ statistic. RESULTS: The times to induction of sedation, recovery, and discharge were shorter in the propofol-fentanyl group than the midazolam-fentanyl group. According to the OAA/S score, deep sedation events occurred in 25% of the propofol-fentanyl group and 11% of the midazolam-fentanyl group (P = 0.014). Additionally, deep sedation events occurred in 19% of the propofol-fentanyl group and 7% of the midazolam-fentanyl group according to the BIS scale (P = 0.039). There was good concordance between the OAA/S score and BIS for both groups (κ = 0.71 and κ = 0.63, respectively). Oxygen supplementation was required in 42% of the propofol-fentanyl group and 26% of the midazolam-fentanyl group (P = 0.025). The mean time to recovery was 28.82 and 44.13 min in the propofol-fentanyl and midazolam-fentanyl groups, respectively (P < 0.001). There were no severe complications in either group. Although patients were equally satisfied with both drug combinations, physicians were more satisfied with the propofol-fentanyl combination. CONCLUSION: Deep sedation occurred with propofol-fentanyl and midazolam-fentanyl, but was more frequent in the former. Recovery was faster in the propofol-fentanyl group.

Evaluation on Efficacy and Safety of Tribromoethanol and Tribromoethanol plus alpha2-Adrenergic Agonists in Different Mouse Strains / 한국실험동물학회지

The present study was carried out to provide a guideline for injecting tribromoethanol (TBE) as the main anesthetic agent, while adjusting the doses of xylazine (X) and medetomidine (M) according to different strains of mice (male ICR, C57BL/6, and BALB/c). Seven intraperitoneal injection anesthesia protocols using TBE and mixtures of TBE and alpha2-adrenergic agonists (TBE/X and TBE/M) were compared in terms of their efficacy and safety (anesthetic duration, death rate, and the development of pathological lesions of abdominal organs). All animals that were injected with a low dose of TBE (200 mg/kg) displayed clear signs of light anesthesia with a strong pedal withdrawal reflex. Despite the good anesthetic effect, a high dose of TBE (400 mg/kg) was not a suitable anesthetic for major surgery in all mouse strains because of the risk of pathologic changes in the abdominal organs, such as retention of the digestive tract, peritonitis, and fibrinoid adhesion. TBE200/X10 and TBE200/M0.5 (TBE, 200 mg/kg; X, 10 mg/kg; M, 0.5 mg/kg) appeared to be safe and provided satisfactory anesthesia in ICR mice. Finally, there were clear differences in anesthetic efficacy among ICR, C57BL/6, and BALB/c strains. TBE/M and TBE/X did not anesthetize BALB/c mice, and it anesthetized C57BL/6 mice for a short time. When administered with TBE/X and TBE/M maintained the sedation of ICR mice. We were able to establish different regimes for each strain (TBE200/X20 for C57BL/6, TBE300/X10 and TBE200/M1 for BALB/c). Our results showed that TBE/X and TBE/M could be recommended as an anesthetic mixture, with the dose appropriately adjusted according to mouse strain.

Evaluation on Efficacy and Safety of Tribromoethanol and Tribromoethanol plus alpha2-Adrenergic Agonists in Different Mouse Strains / 한국실험동물학회지

The present study was carried out to provide a guideline for injecting tribromoethanol (TBE) as the main anesthetic agent, while adjusting the doses of xylazine (X) and medetomidine (M) according to different strains of mice (male ICR, C57BL/6, and BALB/c). Seven intraperitoneal injection anesthesia protocols using TBE and mixtures of TBE and alpha2-adrenergic agonists (TBE/X and TBE/M) were compared in terms of their efficacy and safety (anesthetic duration, death rate, and the development of pathological lesions of abdominal organs). All animals that were injected with a low dose of TBE (200 mg/kg) displayed clear signs of light anesthesia with a strong pedal withdrawal reflex. Despite the good anesthetic effect, a high dose of TBE (400 mg/kg) was not a suitable anesthetic for major surgery in all mouse strains because of the risk of pathologic changes in the abdominal organs, such as retention of the digestive tract, peritonitis, and fibrinoid adhesion. TBE200/X10 and TBE200/M0.5 (TBE, 200 mg/kg; X, 10 mg/kg; M, 0.5 mg/kg) appeared to be safe and provided satisfactory anesthesia in ICR mice. Finally, there were clear differences in anesthetic efficacy among ICR, C57BL/6, and BALB/c strains. TBE/M and TBE/X did not anesthetize BALB/c mice, and it anesthetized C57BL/6 mice for a short time. When administered with TBE/X and TBE/M maintained the sedation of ICR mice. We were able to establish different regimes for each strain (TBE200/X20 for C57BL/6, TBE300/X10 and TBE200/M1 for BALB/c). Our results showed that TBE/X and TBE/M could be recommended as an anesthetic mixture, with the dose appropriately adjusted according to mouse strain.

The minimal local anesthetic dose of bupivacaine for caesarean section in combined spinal-epidural anesthesia determined by up-and-down method / 重庆医科大学学报

Objective:To investigate the minimal local anesthetic dose(MLAD) of bupivacaine for caesarean section in combined spinal-epidural anesthesia(CSEA).Methods:Designed by up-and-down,34 parturients who met the standards were given bupivacaine as planned dose gradient.Hemodynamics were monitored continuously,untoward effects were observed and APGAR of the neonates were given.Results:The MLAD of bupivacaine which is used in CSEA for caesarean section is 5.03 mg(4.1～5.1 mg),and that of ED90 and ED95 are 7.15 mg,7.89 mg respectively.Conclusion:The clinical easy to use dose of bupivacaine is 7.5 mg which is used in CSEA for most parturients.