Three cases of difficulty in achieving definitive loss of consciousness with remimazolam

Background Remimazolam is a novel, ultra-short-acting benzodiazepine used for general anesthesia. Because remimazolam is an emerging drug, the tolerance to remimazolam in benzodiazepine-taking patients has been unclear. Also, the efficacy of remimazolam in different races is not fully elucidated so far. Case presentation Here we experienced three cases in which high dose of remimazolam was needed for attempting to achieve appropriate anesthetic depth. Two of the three cases were of preoperatively benzodiazepine-taking patients. The other was a case of a Chinese patient. In all three cases, conversion to general anesthesia with propofol was necessitated. Conclusions When signs of inadequate sedative effect of remimazolam are observed in patients of benzodiazepine users or of different races, conversion to another sedative agent such as propofol should be considered.

Sedative effect and physiological changes in horses treated with intramuscular injection of detomidine and morphine

ABSTRACT: This study aimed to elucidate the sedative effect and physiological changes associated with the intramuscular injection of detomidine combined with morphine in horses. Six healthy crossbred horses, aged 2 to 10 years, were included. A crossover experimental design was used to compare the effects of intramuscular injection of 30 µg/kg of detomidine alone (IMD) and intramuscular administration of 30 µg/kg of detomidine and 0.1 mg/kg of morphine (IMDM). The degree of sedation, height of head above ground, were assessed at the time points before and 5, 10, 20, 30, 40, 50, 60, 75, 90, 105, and 120 minutes after drug administration, and heart rate, respiratory rate, systolic blood pressure, rectum temperature and intestinal motility were assessed at the time points before and 10, 20, 30, 40, 50, 60, 75, 90, 105, and 120 minutes after drug administration. The physiological parameters were analyzed using the Kruskal-Wallis test with Dunn’s post-hoc test and analysis of variance with t-test for independent samples and the sedation scores using the Friedman test and Mann Whitney U-test. P-values <0.05 indicated a statistically significant difference. IMDM promoted a higher sedative effect as compared to IMD, but the sedation occurred inconsistently. Additionally, a reduction in intestinal motility was observed with IMDM at 60, 75, 90, and 105 minutes after administration. IMDM promoted more variable sedation and prolonged reduction in the intestinal motility in the horses as compared to IMD.

Experience of Dexmedetomidine using for intraoperative analgosedation during ophthalmic operations

Background. The aim of the study is to evaluate the quality and safety of the sedative effect of anesthesia in ambulant ophthalmic surgery by using continuous intravenous infu­sion of Dexmedetomidine. Materials and Methods. Patients were randomized into groups by age (people from 65 to 75 years old, old age 76 years, middle age, young people, children), by gender (men, women). The physical status of patients was assessed using the ASA scale and the dynamics of vegetatic activity by the Kerdo index. Sedation was assessed using the Richmond Sedation Scale RASS.Results. It was found that the difference in the frequency of adverse effects of the appointment of Dexmedetomidine clearly confirms the need to adjust the dose of Dexmede­tomidine, depending on the state of the autonomic nervous system. The use of Dexmedetomidine according to the rec­ommendations made it possible to achieve a safe level of sedation and eliminate side effects in ambulant ophthalmic surgery.Conclusions: Parenteral continuous infusion of Dexmedetomidine pro­vides an effective level of sedation for ambulant ophthalmic surgery and maintaining patient­surgeon contact. Safety is confirmed by a low level of critical incidents, no respiratory depression at the target sedation level. The patency of the upper airways was better compared to previous experience with propofol.

Combination of Dexmedetomidine and Tramadol in Patient-Controlled Intravenous Analgesia Strengthens Sedative Effect in Pregnancy-Induced Hypertension

Objective: The aim of the present study is to explore the combination of dexmedetomidine (DXM) and tramadol (TMD) on sedative effect in patients with pregnancy-induced hypertension (PIH).Methods: A total of 356 patients with pregnancy-induced hypertension (PIH) were randomly divided into three groups: DXM, TMD and DXM + TMD groups. These patients were treated with different doses of DXM, TMD or combination of DXM and TMD by a patient-controlled intravenous injection device. The scores of static pain and dynamic pain, sedation degree, and adverse reaction were recorded. The plasma levels of inflammatory mediators IL-10 and C-reactive protein (CRP), and the serum level of p-p38-MAPK were evaluated.Results: It was found that administration with DXM 1.0 µg/kg/h + TMD 700 mg and DXM 2.0 µg/kg/h + TMD 600 mg result in stronger sedative effect than single administration with DXM or TMD. The mean arterial pressure (MAP) and heart rate (HR) of patients with PIH were decreased with the combinational treatment of DXM and TMD. Interestingly, the PIH patients injected with DXM 1.0 µg/kg/h + TMD 700 mg and DXM 2.0 µg/kg/h + TMD 600 mg showed stronger sedative effect. In addition, the plasma level of level of IL-10 was increased and CRP decreased. The serum level of p-p38/MAPK was decreased.Conclusion: Taken together, our study indicates that combination of DXM and TMD effectively lowers blood pressure and reduces inflammation through increasing the level of IL-10, reducing CRP and inhibiting p-p38/MAPK in patients with PIH. This study suggests that the combination of DXM and TMD could be an anesthetic choice in the management of PIH.

Comparative Study between Nitroglycerine, Magnesium Sulfate and Dexmedetomidine to Induce Hypotension During Functional Endoscopic Sinus Surgery (FESS)

Background Functional Endoscopic Sinus Surgery (FESS) has been employed as a surgical intervention to treat chronic rhinosinusitis in patients with no response to drug therapy, during which the surgical vision may be greatly reduced by a small amount of bleeding. There by, the intraoperative controlled hypotension can improve the visibility. While excessive bleeding intraoperative cause serious complications in the postoperative period, including eye socket infections, visual acuity damage, meningeal infections, and other. Objective Induced hypotension limits intra operative (IO) blood loss provides better visibility of the surgical field and diminishes the incidence of major complications during Functional Endoscopic Sinus Surgery (FESS). We aimed at comparing Nitroglycerine; Magnesium Sulfate and Dexmedetomidine for inducing controlled hypotension and evaluate narcotic used, mac of inhalational anesthesia, and Ramsay Sedation Scale (RSS) in the recovery and pre-anesthetic time in patients undergoing Functional Endoscopic Sinus Surgery (FESS). Patients and Methods This study was conducted on 75 patients who underwent elective functional endoscopic sinus surgery (FESS) who matched the inclusion criteria and were randomly allocated into 3 groups each containing 25 patients. The first group received loading dose of dexmedetomidine 1μg/kg infused over 10 min before induction of anesthesia then 0.7 μg/kg/h via syringe pump, second group received nitroglycerine infusion at a dose of 2μg/kg/min according to the response started after induction, intubation, positioning and sterilization of the patient and third group received a loading dose of magnesium sulfate 40 mg/kg over 10 minutes followed by an infusion 15mg/kg/h via syringe pump. Results The result of our study showed that dexmedetomidine, magnesium sulfate, or nitroglycerine successfully induced deliberate hypotension and were effective in providing good surgical field during FESS, but dexmedetomidine showed superior hemodynamic profile. Compared with nitroglycerine, both dexmedetomidine and magnesium sulfate offered the advantage of inherent analgesic and sedative effect. Conclusion Dexmedetomidine, magnesium sulfate, or nitroglycerine successfully induced deliberate hypotension and were effective in providing good surgical field during FESS, but dexmedetomidine showed superior hemodynamic profile. Compared with nitroglycerine, both dexmedetomidine and magnesium sulfate offered the advantage of inherent analgesic and sedative effect. Dexmedetomidine also showed shorter duration of surgery with less blood loss and favorable frommer score with more surgeon satisfaction. Dexmedetomidine showed longest time to 1st analgesic rescue in PACU comparing with magnesium sulfate and nitroglycerine. So, it’s advised to use dexmedetomidine to induce hypotension than magnesium sulfate and nitroglycerine. However, dexmedetomidine should be used with caution as it caused hypotension and bradycardia, t had sedative effect with low aldert score comparing with nitroglycerine and magnesium sulfate.

The Balance Between the Effectiveness and Safety for Chemotherapy-Induced Nausea and Vomiting of Different Doses of Olanzapine (10 mg Versus 5 mg): A Systematic Review and Meta-Analysis

IntroductionThe aim of this study is to rigorously review the efficacy and safety of olanzapine in chemotherapy-induced nausea and vomiting (CINV) settings including (1) at 5- and 10-mg doses, and (2) the setting of highly emetogenic chemotherapy (HEC) and moderately emetogenic chemotherapy (MEC).MethodsEmbase, Pubmed, and Cochrane Library were searched from the establishment of the database through April 18, 2021. The primary efficacy endpoints were the rate of complete response (CR; no emesis and no rescue), in the acute (0–24 h post-chemotherapy), delayed (24–120 h post-chemotherapy), and overall (0–120 h post-chemotherapy) phases. The secondary efficacy endpoints were the rates of complete control (CC, no nausea, and no emesis), for each phase. Safety endpoints were the rate of somnolence, as assessed by Common Terminology Criteria for Adverse Events (CTCAE) criteria. The Mantel–Haenszel, random, or fixed-effect analysis model was used to compute risk ratios and accompanying 95% confidence intervals for each endpoint. For endpoints that statistically favored one arm, absolute risk differences were computed to assess whether there is a 10% or greater difference, used as the threshold for clinical significance by MASCC/ESMO.ResultNine studies reported the use of 10 mg olanzapine to prevent CINV; three studies reported the use of 5 mg olanzapine to prevent CINV. When olanzapine was administered at 10 mg for HEC patients, the six endpoints were statistically and clinically better than the control group. For MEC patients, four out of six endpoints were better than the control group. When olanzapine is administered at 5 mg for MEC patients, four endpoints have statistical and clinical advantages. The sedative effects of 10 and 5 mg olanzapine were statistically more significant than those of the control group. The sedative effect of the 10-mg olanzapine group was more significant than that of the 5-mg olanzapine group, both statistically and clinically.Conclusion5 mg olanzapine may be as effective as 10 mg olanzapine for patients with HEC and MEC, and its sedative effect is lower than 10 mg olanzapine. Fewer studies on 5 mg olanzapine have led to uncertain data. In the future, more randomized controlled trials of 5 mg olanzapine are needed to study the balance between the effectiveness and safety of olanzapine.

Robust behavioural effects in response to acute, but not repeated, terpene administration in Zebrafish (Danio rerio)

Terpenes are fragrant aromatic compounds produced by a variety of plants, most notably cannabis and hops. With increasing legalization of cannabis there is a need to better understand the behavioural effects of terpenes and ultimately their therapeutic value. Our study investigated the dose-dependent impact of three terpenes (limonene 0.25, 0.5, 0.75%; β-myrcene 0.001, 0.01, 0.1%; and 0.0001, 0.001, 0.00125% linalool) on zebrafish (Danio rerio) behaviour when exposed both acutely and repeatedly over a 7-day period. Anxiety-like behaviour, boldness, and locomotion were assessed using the open field test and the novel object approach test. In the acute dosing experiment, limonene and β-myrcene exposed groups demonstrated a significant decrease in locomotion, a decrease in anxiety-like behaviour, and an increase in boldness, while linalool treatment groups demonstrated only minor alterations in locomotion. Moreover, repeated exposure to limonene (0.39%) or β-myrcene (0.0083%) for a seven day period did not result in any significant behavioural effects. In conclusion, our study provides support for an anxiolytic and sedative effect in zebrafish in response to acute limonene and β-myrcene exposure that is no longer present after one week of repeated exposure.

A Comprehensive Evaluation Between Dexmedetomidine and Midazolam for Intraoperative Sedation in the Elderly: Protocol for a Systematic Review and Meta-analysis of Randomized Controlled Trials

Background: The sedative effect of intraoperative sedation in elderly surgery exerts critical influence on the prognosis. Comparison on the safety and efficacy between Dexmedetomidine and Midazolam in many clinical randomized controlled trials (RCTs) were inconsistent and suspicious. We aimed to comprehensively evaluate the safety and efficacy between Dexmedetomidine and Midazolam for intraoperative sedation in the elderly via meta-analysis and systematic reviews.Methods: RCTs regarding to the comparison of sedative effects and safety between Dexmedetomidine and Midazolam in elderly patients (aged ≥ 60 years) will be comprehensively searched from 2000.10 to 2021.05 through 4 English databases and 4 Chinese databases. After extraction in duplicate, the systematic review and meta-analysis will be performed on the primary outcomes (hemodynamic changes, sedative effect, cognitive function) and secondary outcomes (analgesic effect, surgical characteristics, complications or adverse reactions) for assessing the two therapy methods using Review manage software (Version 5.3). Sensitivity analysis will be conducted to evaluate the heterogeneity of the results, funnel plot and Egger’s test will be performed to analyze publication bias of the included studies, and test sequential analysis will be applied to assess the robustness and reliability of preliminary meta-analysis results. Finally, rating quality of evidence and strength of recommendations on the meta results will be summarized by rating quality of evidence and strength of recommendations (GRADE) approach. Discussion: This systematic review and meta-analysis will evaluate the safety and efficacy between Dexmedetomidine and Midazolam for intraoperative sedation in the elderly, it will give an insight on the application of Dexmedetomidine and Midazolam, and will provide evidences-based reference for clinical decision makings.Systematic review registration: PROSPERO (CRD42021221897).

Studies on the Sedative Effect of Mitragyna speciosa Korth. as an Endemic Plant in West Borneo, Indonesia

Kratom (Mitragyna speciosa Korth.) is an endemic plant of West Borneo (Indonesia). One of its uses in the community is as a sedative. The aim of this research is to determine the effective dose of kratom leaf extract and infusion against male BALB/c mice. The traction test and fireplace test methods were used to determine the sedative effect quantitatively. The qualitative test was carried out by observing the corneal reflex and the body turning reflex. Mice were divided into 5 groups, namely positive control group (diazepam), negative control (CMC 1% + aqua dest), ethanol extract group 12.14 mg/ 20gBB, ethanol extract group 24.29 mg/ 20gBB, ethanol extract group 48.57 mg/ 20gBB, kratom leaf infusion group 39 mg/ 20gBB, kratom leaf infusion group 78 mg/ 20gBB, and kratom leaf infusion group 156 mg/ 20gBB. The results showed that the ethanol extract and infusion of kratom leaf had a sedative effect on male BALB/c mice. The effective doses of ethanolic extract and kratom leaf infusion are 48.57 mg / 20gBB and 156mg / 20g BW, respectively. Kratom leaf ethanolic extract has more potential sedative effect than diazepam as a positive control, whereas kratom leaf infusion is the opposite.

Maclura tinctoria Extracts: In Vitro Antibacterial Activity against Aeromonas hydrophila and Sedative Effect in Rhamdia quelen

Maclura tinctoria is a tree species native from Brazil and rich in phenolic compounds. Since plant antibacterial activity is highly associated with phenolic compound concentration, we aim to evaluate the in vitro antimicrobial activity of different extracts against fish pathogenic bacteria. In addition, some phenolic compounds have central depressant effects and can be useful in aquaculture due to possible sedative and/or anesthetic effects. Four M. tinctoria extracts were extracted separately with ethanol; leaves (LE), bark (BE), heartwood (HE), and the sapwood (SE). In vitro antimicrobial activity was tested against Aeromonas strains at concentrations of 6400 to 3.125 μg/mL. The sedative effect was evaluated for 24 h with 30 and 100 mg/L concentrations. Chemical composition was analyzed by HPLC-DAD-MS. The HE extract had the best MIC (400 µg/mL) and MBC (800 µg/mL) compared to the LE, BE, and SE extracts. LE extract induced deep sedation and the BE, SE, and HE extracts induced light sedation. Additionally, BE, SE, and HE induced a normal behavior without side effects. Polyphenolic compounds with antimicrobial activity and sedative effects were identified mainly in HE. Thus, HE extract is safe and can be used as a sedative for silver catfish.