The use of midazolam combined with dexmedetomidine for MRI sedation in children / 中国现代医生

@#Objective To evaluate the efficacy and safety of midazolam combined with dexmedetomidine for sedation during magnetic resonance imaging(MRI)examination in children.Methods The medical records of children who underwent sedated MRI examinations at the Sedation Center of Children's Hospital Affiliated to Shandong University from August 2021 to July 2022 were collected.The patients were divided into three groups based on age:Infant group(age≤1 year old,922 cases),toddler group(1 year old<age≤3 years old,1153 cases),and child group(3 years old<age≤8 years old,1698 cases).The sedation regimen was oral midazolam solution 0.5mg/kg combined with intranasal dexmedetomidine 2μg/kg.Medication taken 30 minutes prior to MRI examination.The sedation depth was evaluated using the Ramsay sedation scale.A score of≥5 points was considered to achieve deep sedation.The general data,sedation success rate,sleep time,wake time and the occurrence of adverse reactions were analyzed.Results The total number of children included in the analysis amounted to 3773,with 3480 cases successfully sedated,with a total success rate of 92.2%.The success rate of 15min and 30min sedation in child group was significantly lower than that in infant group and toddler group(P<0.05).The success rate of 45min and 60min sedation in toddler group was significantly lower than that in infant group and child group(P<0.05).The sleep time in child group was significantly longer than that in infant group and toddler group(P<0.001).The recovery time of infant group was longer than that of toddler group and child group(P<0.001).The overall incidence of adverse reactions was 4.9%.The incidence of total adverse reactions in child group was significantly lower than that in infant group and toddlers group(P<0.001).Conclusion Oral midazolam combined with intranasal dexmedetomidine is safe and effective for sedation during MRI examinations in children.The younger the age,the higher the sedation success rate,the longer the recovery time,but the overall incidence of adverse reactions is low.This combination of drugs is a safe and effective sedation option for pediatric MRI examinations.

Meta-analysis of efficacy and safety of sedative therapy with midazolam and dexmedetomidine/propofol in critically ill patients undergoing mechanical ventilation / 中国药房

OBJECTIVE To systematically evaluate the efficacy and safety of midazolam and dexmedetomidine/propofol for the sedation of critically ill patients undergoing mechanical ventilation， and to provide evidence-based reference for clinical treatment. METHODS Retrieved from PubMed， Embase， Web of Science， Cochrane Library， Clinical trials. gov， China Journal Full Text Database， Chinese Science and Technology Journal Database， Wanfang database and China Biomedical Literature Database， the data on the efficacy and safety of midazolam and dexmetomidine/propofol for the sedation of critically ill patients undergoing mechanical ventilation were collected from the establishment of the database to March 31， 2023. After extracting data from clinical studies that met the inclusion criteria， the meta-analysis was conducted by using the RevMan 5.3 statistical software. RESULTS A total of 31 literature were included， with a total of 2 765 patients. Results of meta-analysis showed that the mechanical ventilation time [MD＝14.13， 95%CI （13.75， 14.52）， P＜0.000 01] and the length of hospitalization in the intensive care unit [MD＝0.92， 95%CI （0.54， 1.30）， P＜0.000 01] of patients in the midazolam group was longer than dexmedetomidine/ propofol group. The incidence of bradycardia in midazolam group was lower dexmedetomidine/propofol group [OR＝0.60， 95%CI （0.41， 0.90）， P＝0.01]， but there was no statistically significant difference in the incidence of hypotension between the two groups [OR＝0.69， 95%CI （0.47， 1.01）， P＝0.06]. The incidence of delirium [OR＝3.88， 95%CI （2.74， 5.49）， P＜0.000 01]， ventilator- associated pneumonia [OR＝2.32， 95%CI （1.19， 4.51）， P＝0.01]， and respiratory depression [OR＝5.70， 95%CI （3.09， 10.52）， P＜0.000 01] in midazolam group were higher than dexmedetomidine/propofol group. CONCLUSIONS Compared with dexmedetomidine/propofol， midazolam increases patients’ mechanical ventilation time and the length of hospitalization in the intensive care unit in terms of efficacy， and increases the risk of delirium and pulmonary complications in terms of safety， but has a smaller cardiovascular impact.

Midazolam alleviates neuronal damage induced by oxygen glucose deprivation/restoration in mice / 基础医学与临床

Objective To investigate the impact of midazolam on neuronal injury induced by oxygen glucose depri-vation/reoxygenation(OGD/R)in mice.Methods An injury model of neuronal cell line HT22 was established by OGD/R induction.HT22 cells were divided into OGD/R group,low-dose group,medium-dose group and high-dose group,midazolam+KG-501(CREB inhibitor)group and control group.ELISA was applied to detect TNF-α and IL-6 levels;Commercialy available reagent kits were applied to detect superoxide dismutase(SOD),catalase(CAT),and malondialdehyde(MDA)levels;MTT and Edu experiments were applied to detect cell prolifera-tion;flow cytometry was applied to detect cell apoptosis rate;RT-qPCR method was applied to detect the ex-pression levels of CREB mRNA and PGC-1α mRNA;Western blot was applied to detect the expression levels of Ki-67,Bcl-2,Bax,CREB,and PGC-1α proteins.Results Compared with the control group,the A490 value(24,48 hours),proliferation rate,SOD and CAT activity,CREB mRNA and PGC-1α mRNA expres-sion,Ki-67,Bcl-2,CREB,and PGC-1α protein level in the OGD/R group were all significantly reduced(P＜0.05);The apoptosis rate,TNF-α,IL-6,MDA,and Bax protein expression were significanty increased(P＜0.05).Compared with the OGD/R group,the A490 values(24,48 hours),proliferation rate,SOD,CAT activity,CREB mRNA and PGC-1α mRNA expression,and Ki-67,Bcl-2,CREB,and PGC-1α protein expression were significantly increased in low,medium,and high dose midazolam groups;The apoptosis rate,TNF-α,IL-6,MDA,and Bax protein expression were obviously reduced(P＜0.05).Compared with the high-dose midazolam group,A490 value(24,48 hours),proliferation rate,activity of SOD and CAT,CREB mRNA and PGC-1α mRNA expression as well as Ki-67,Bcl-2,CREB,and PGC-1α protein expression were all sig-nificantlu reduced in the high-dose midazolam+KG-501 group while the apoptosis rate,TNF-α,IL-6,MDA,and Bax protein expression were obviously increased(P＜0.05).Conclusions Midazolam might alleviate nerve cell injury potentially through the mechaninsms of promoting OGD/R-induced proliferation and reducing cell apoptosis in HT22 cells.

Effect of midazolam on postoperative delirium in elderly patients with preoperative moderate-severe anxiety undergoing radical resection of colorectal cancer / 临床麻醉学杂志

Objective To investigate the effect of preoperative oral midazolam on postoperative de-lirium in elderly patients with preoperative moderate-severe anxiety undergoing radical resection of colorectal cancer.Methods Eighty elderly patients undergoing laparoscopic surgery for radical resection of colorectal cancer,32 males and 48 females,aged 65-79 years,BMI 21-27 kg/m2,ASA physical status Ⅱ or Ⅲ,the state-trait anxiety inventory(STAI-S)≥38 scores at admission were selected.Patients were divided into two groups using random number method:control group and midazolam group,40 patients in each group.The midazolam group were administrated midazolam 7.5 mg per night till one day before surgery,while the placebo was administrated in the control group.The incidence of delirium 3 days after surgery and the STAI-S scores of one day before surgery were evaluated.The HR and MAP at entry,30 minutes after an-esthesia induction,1 hour,2 hours after anesthesia induction,and 30 minutes after extubation were recor-ded.The total dose of propofol,remifentanil and dexmedetomidine and the using rate of metaraminol were recorded.The visual analog scale scores 30 minutes after extubation,24 and 72 hours after surgery,the u-sing rate of tramadol,and the extubation time were recorded.Results Compared with the control group,the STAI-S scores of one day before surgery,and the incidence of postoperative delirium,the rate of using metaraminol,the VAS scores 30 minutes after extubation and 24 hours after surgery,the rate using of tram-adol were significantly decreased in the midazolam group(P＜0.05).There were no significant differences in total dose of propofol,remifentanil,and dexmedetomidine,extubation time between the two groups.Conclusion Preoperative oral midazolam can effectively reduce the incidence of postoperative delirium in elderly patients with preoperative moderate-severe anxiety undergoing radical resection of colorectal cancer.

Psychological dependence liability of gaboxadol in two-bottle free-choice model in mice / 中国药理学与毒理学杂志

OBJECTIVE To evaluate the psychological dependence of the extrasynaptic GABAA receptor(GABAAR)agonist gaboxadol and compare it with the synaptic GABAAR modulator midazolam in the two-bottle free-choice model of mice.METHODS ① Male C57BL/6J mice were ig administered with vehicle,midazolam(59.0,73.7,92.2,115.2,144.0 and 180.0 mg·kg-1)or gaboxadol(8.4,10.5,13.1,16.4,20.5,25.6 and 32.0 mg·kg-1),and the loss of righting reflex was observed.The median effective dose(ED50)was obtained from the dose-response curve.② A two-bottle free-choice model was used to find out whether gaboxadol and midazolam induced preference behavior in mice.The mice were divided into normal control,gaboxadol or midazolam groups.During the habituation stage(the first day to the third day,D1-D3),both test and vehicle bottles contained water.During the trail stage(D4-D5),4%sucrose solution was provided in both bottles.During the test stage(D6-D15),test bottles contained vehicle,gaboxadol(3.9×10-6 mol·L-1)or midazolam(1.4×10-5 mol·L-1)in sucrose solu-tions,while other bottles contained the corresponding vehicle in sucrose solutions.Bottles were placed on the two sides of the home cage,to which mice had free access,and their consumption from each bottle was recorded daily.Total consumption,accumulated daily consumption,relative consumption,and accumulated relative consumption during the test stage were calculated.The weight of the mice was also recorded.RESULTS ① Midazolam and gaboxadol dose-dependently increased the rate of loss of right reflex in mice,with ED50 of 105.3 mg·kg-1(95%CI:96.4-115.2 mg·kg-1,R2=0.9796),13.7 mg·kg-1(95%CI:12.6-15.0 mg·kg-1,R2=0.9773),respectively.② Compared with the normal control group,there was no significant difference in the total consumption in the gaboxadol and midazolam groups.Compared to the vehicle bottles,the daily consumption from test bottles in the midazolam group increased significantly on D11-D15 of the test stage(P<0.05),while daily consumption from gaboxadol test bottles was significantly higher than that of vehicle bottles(P<0.01).Compared with the normal control group,the daily relative consumption in the gaboxadol group was significantly increased on D9(P<0.05),and the accumulative relative consumption was significantly higher than in the normal control group(P<0.01).There was no significant change in body weight across the groups over the test stage.CONCLU-SION Like midazolam,gaboxadol exhibits psychological dependence potential in a two-bottle free-choice model.

Efficacy of oral midazolam solution for preoperative sedation in pediatric outpatients undergoing root canal treatment under general anesthesia / 中华麻醉学杂志

Objective:To evaluate the efficacy of oral midazolam solution for preoperative sedation in the pediatric outpatients undergoing root canal treatment under general anesthesia.Methods:One hundred and forty-seven pediatric patients of either sex, aged 2-7 yr, weighing 10-30 kg, of American Society of Anesthesiologists Physical Status classificationⅠ or Ⅱ, were divided into 3 groups ( n=49 each) using a random number table method: oral midazolam solution group (OM group), midazolam injection group (M group), and dexmedetomidine group (D group). In OM group, patients received oral midazolam solution at a dose of 0.5 mg/kg along with a placebo (an equivalent amount of normal saline based on body weight) administered via nasal drops. In M group, patients were given oral midazolam injection at a dose of 0.5 mg/kg along with a placebo via nasal drops. In D group, patients were administered a placebo orally along with dexmedetomidine at a dose of 2 μg/kg via nasal drops. The Induction Compliance Checklist (ICC) scores upon entering the operating room, sedation success rates (ICC score ≤ 3), drug acceptance scores, mask acceptance scores, and separation anxiety scores were recorded. The emergence time, time of stay in postanesthesia care unit (PACU), and occurrence of adverse events such as bradycardia, hypotension, hypoxemia, and laryngospasm during surgery and in PACU were recorded. Results:A total of 143 pediatric patients were finally included in the study, with 48 cases in OM group, 48 cases in M group and 47 cases in D group. Compared with M and D groups, the ICC scores upon entry to the operating room were significantly decreased, the sedation success rates were increased, drug acceptance scores were increased, separation anxiety scores were decreased, and mask acceptance scores were decreased in OM group ( P<0.05). Compared with D group, the ICC scores upon entry to the operating room were significantly decreased, the sedation success rates were increased, and mask acceptance scores were decreased in M group ( P<0.05). There were no statistically significant differences in the emergence time, time of stay in PACU, and incidence of adverse events during surgery and in PACU among the three groups ( P>0.05). Conclusions:Oral midazolam solution provides good effect with less adverse reactions when used for preoperative sedation in the pediatric outpatients undergoing root canal treatment under general anesthesia.

Effect of Continuous Infusion of Midazolam on Refractory Headache and/or Nausea in Patients with Intracranial Cancer Lesions

Objective: To investigate the effectiveness and safety of continuous infusion of midazolam for the treatment of headache and/or nausea/vomiting in patients with brain tumors or cancer-associated meningitis. Methods: Patients who presented with headache and/or nausea/vomiting and underwent continuous infusion of midazolam from April 2005 to March 2021 were retrospectively analyzed. Results: Among 22 patients, 19 presented with headache and 14 with nausea/vomiting. The success rate of continuous infusion of midazolam for headache was 89% and that for nausea/vomiting was 78%. The mean number of vomiting episodes within 24 hours from the start of midazolam administration was 0.14±0.36, which was significantly lower than that from 24 hours before to the start of administration (1.43±1.60, P=0.015). Sedation was observed as an adverse event in five (23%) patients, but no patients developed respiratory depression. Conclusion: When conventional therapies are ineffective for headache and/or nausea/vomiting caused by brain tumors or cancer-associated meningitis, continuous infusion of midazolam may improve symptoms and should be considered as a treatment option.

Effects of the timing of satisfactory sedation with preoperative oral midazolam on anesthesia induction and recovery in children undergoing adenotonsillectomy / 中国临床药理学与治疗学

AIM: To investigate the effect of the timing of satisfactory sedation with preoperative oral midazolam on anesthesia induction and recovery in children undergoing adenotonsillectomy. METHODS: A total of 147 children undergoing elective adenotonsillectomy, with ASA physical status orⅡ, aged 2-7 years were selected from November 2022 to June 2023 in the Second Affiliated Hospital of Wenzhou Medical University. The children were orally administered 0.5 mg/kg midazolam in preoperative waiting area and were divided into 10-20 min (rapid onset, M1 group) and 21-30 min (slow onset, M2 group) based on the satisfactory sedation time, or equal volume of sugar pear drink orally (blank control group, C group). Children in all three groups received a general anesthesia method of propofol+fentanyl combined with sevoflurane induction and sevoflurane maintenance. The primary outcome measures were the induction compliance checklist (ICC) score and the pediatric anesthesia emergence delirium (PAED) score in the post-anesthesia care unit (PACU) to assess the occurrence of emergence agitation (EA), and the secondary outcome measures included the parental separation anxiety scale (PSAS), sedation Ramsay score, surgery duration, recovery time, PACU stay time, discharge time, the incidence of perioperative respiratory adverse events (PRAE) and other adverse events in the ward. RESULTS: 147 children were included in the result analysis, with 49 cases in each group. The proportion of perfect induction (ICC=0) were significantly higher in two M groups than that in group C (95.9% vs. 91.8% vs. 61.2%, P=0.001). The maximum and average PAED score in PACU in group M1 showed a significantly higher (6.4±5.0 vs. 4.4 ± 4.1, P=0.029; 5.2 ± 4.5 vs. 3.4 ± 3.6, P=0.030), and the incidence of EA was significantly higher than those in group C (10.2% vs. 30.6%, P=0.022), and increased compared to the group M2 (OR= 0.581, 95%CI 0.231-1.463, P=0.354). There was no statistically significant difference in the maximum and average PAED scores, incidence of EA between group M2 and group C (P>0.05). The Ramsay score and PSAS score in two M groups were higher, PACU stay time and recovery time was longer than those in group C (P0.05). CONCLUSION: Preoperative oral midazolam can improve the ICC and PSAS scores of children during induction, but it also leads to prolonged recovery time and PACU retention time. The rapid onset of midazolam did not result in better induction and recovery quality, but instead increased the incidence of EA and postoperative pain score.

Comparison of Efficacy and Safety of Midazolam versus Nitrous Oxide as Sedative Agents during Paediatric Dental Treatment: A Systematic Review / Comparison of Efficacy and Safety of Midazolam versus Nitrous Oxide as Sedative Agents during Paediatric Dental Treatment: A Systematic Review

ABSTRACT Objective: To identify and study the existing literature on the efficacy and safety of midazolam compared to inhalation of nitrous oxide in children undergoing dental treatment. Material and Methods: Electronic resources such as PubMed Central, Cochrane Database of Systematic Reviews, Lilacs, Science Direct, and SIGLE were thoroughly searched. The title scan was used to find randomised controlled trials reviewed for inclusion by reading the abstract. Studies comparing the sedative, behavioural, and anxiolytic effects and safety in children undergoing dental treatment under midazolam and nitrous oxide inhalation were included. The Cochrane Reviews system software, Revman 5.4.1, was used to assess the quality of the included studies. Results: 11328 articles were identified by screening the electronic databases, of which 10906 were eliminated after titles were read and duplicates were removed. Ten full-text articles were examined, of which three were excluded as they did not match the eligibility criteria. Hence, a total of 7 studies were included. Midazolam and nitrous oxide inhalation were not statistically different in terms of the success of treatment and behaviour modification. However, midazolam showed a deeper level of sedation and resulted in amnesia in more children when compared to nitrous oxide sedation. All of the included studies were found to have a high risk of bias. Conclusion: Though all the studies included showed an increased risk of bias, midazolam and nitrous oxide inhalation seem equally effective sedative agents for controlling behaviour in children undergoing dental treatment. Midazolam shows a deeper sedation level when given orally and produces a higher rate of anterograde amnesia.

Effect of combined use of midazolam and remifentanil without muscle relaxants on tracheal intubation in female patients undergoing breast surgery / 中国基层医药

Objective:To investigate the effect of combined use of midazolam and remifentanil without muscle relaxant on tracheal intubation in female patients undergoing breast surgery.Methods:A retrospective analysis was performed on 40 female patients with breast disease who underwent tracheal intubation and general anesthesia at The First Affiliated Hospital of Zhengzhou University between January 2023 and June 2023. These patients were divided into a control group ( n = 20) and an observation group ( n = 20) based on whether muscle relaxants were applied at the time of intubation. The control group received intravenous rocuronium bromide, whereas the observation group did not use muscle relaxants. Both groups were intravenously administered midazolam (0.1 mg/kg) and remifentanil (4 μg/kg) prior to tracheal intubation. The intubation conditions were evaluated based on factors such as the ease of inserting the laryngoscope and the patient's response to intubation, including coughing. Results:There were no statistically significant differences in age, height, and body mass between the two groups (all P > 0.05). The excellent rate of intubation conditions was significantly lower in the observation group compared with the control group [45% (9/20) vs. 85% (17/20), χ2 = 7.03, P = 0.008). The good rate of intubation conditions was significantly higher in the observation group compared with the control group [40% (8/20) vs. 5% (1/20), χ2 = 7.03, P < 0.05]. There was no statistically significant difference in the excellent and good rates of intubation conditions between the observation and control groups [85% (17/20) vs. 90% (18/20), χ2 = 0.23, P > 0.05]. No significant difference in intraoperative awareness score was observed between the observation and control groups [(2.59 ± 0.44) points vs. (2.61 ± 0.31) points, P > 0.05]. None of the patients in either group exhibited any episodes of arrhythmias. Furthermore, no adverse reactions such as muscle stiffness, nausea, vomiting, or skin itching were observed in either group following the surgical procedure. Conclusion:Without the use of muscle relaxants, intravenous administration of midazolam at 0.1 mg/kg and remifentanil at 4 μg/kg for tracheal intubation in female patients undergoing breast surgery can offer excellent intubation conditions, ensuring that the patient remains unconscious throughout the surgical procedure.

Comparison of the effect of adding midazolam versus fentanyl to intrathecal levobupivacaine in patients undergoing cesarean section: double-blind, randomized clinical trial

Abstract Background: Many adjuvants are added to prolong the effects of spinal analgesia. We investigated the postoperative analgesic efficacy of the addition of midazolam or fentanyl to intrathe-cal levobupivacaine in women undergoing cesarean delivery. Methods: Eighty patients were randomly assigned to two groups (n = 40). Group M received 10 mg of 0.5% levobupivacaine plus 2 mg of midazolam. Group F received 10 mg of 0.5% levobupivacaine plus 25 μg of fentanyl. Assessments included motor and sensory block, APGAR score, time to first request for analgesia, postoperative pain score, total consumption of rescue analgesics, and adverse effects. Results: Sensory blockade was prolonged in Group M compared with Group F (215.58 ± 27.94 vs. 199.43 ± 19.77 min; p = 0.004), with no differences in other characteristics of the spinal block in intraoperative hemodynamics or APGAR score. The mean time to first request for rescue analgesia was longer in Group M (351.45 ± 11.05 min) than in Group F (268.83 ± 10.35 min; p = 0.000). The median total consumption of rescue analgesics in the first 24 hours postoperatively was 30 mg in Group M vs. 60 mg in Group F (p = 0.003). The median Visual Analog Scale (VAS) scores were lower in Group Ethan in Group F from the 8th to the 12th hour postoperatively, with no differences between the groups at other time points. The incidence of adverse effects was higher in Group F than in Group M. Conclusion: Intrathecal midazolam (2 mg) was superior to intrathecal fentanyl (25 μg) in increasing the duration of the sensory blockade and postoperative analgesia with lower postoperative pain scores and decreasing the incidence of adverse effects.

Evaluation of Cardiovascular Parameters of ASA I and ASA II Patients Undergoing Dental Implant Surgery Under Intravenous Sedation with Midazolam: A Retrospective Analysis

The purpose of this research was to compare the vital signs of ASA II patients undergoing dental implant surgery under intravenous anesthesia to those of ASA I patients. From a specialist course in Implant Dentistry, 41 medical records (22 ASA I and 19 ASA II patients) were analyzed. Age, gender, ASA classification, blood pressure, heart rate, and oxygen saturation were all measured. Pre-surgery, following the onset of local anesthetic, at the end of the initial implant insertion, and at the end of surgery were all used to collect vital signs. Student's t-test (p<0.05) was used to determine inter- and intra-group data associations. The crossing of operative moments pre-surgical and installation of the first implant in both systolic (p<=0.01) and diastolic (p<=0.03) pressure was statistically significant in ASA I patients. In contrast, there was only a statistical difference in the verification of peripheral oxygen saturation data at preoperative and local anesthesia times in ASA II patients (p<=0.04). When comparing the time of installation of the first implant (p<=0.03) and at the end of surgery (p<=0.02), with respect to systolic pressure, ASA II presented statistically higher, while variable oxygen saturation at the beginning of local anesthesia in ASA I was statistically higher (p<=0.04). It is proposed that intravenous sedation acts in a compensatory manner in patients with systemic disease, leading both groups' behavior to be similar.

El propósito de esta investigación fue comparar los signos vitales de pacientes ASA II sometidos a cirugía de implante dental bajo anestesia intravenosa con los de pacientes ASA I. Se analizaron 41 historias clínicas de un curso de especialista en Implantología (22 pacientes ASA I y 19 ASA II). Se midieron la edad, el sexo, la clasificación ASA, la presión arterial, la frecuencia cardíaca y la saturación de oxígeno. Se tomarn los signos vitales antes de la cirugía, después del inicio de la anestesia local, al final de la inserción inicial del implante y al final de la cirugía. Se utilizó la prueba t de Student (p<0,05) para determinar las asociaciones de datos entre e intragrupos. El cruce de los momentos operatorios prequirúrgicos y de instalación del primer implante tanto en la presión sistólica (p<=0,01) como en la diastólica (p<=0,03) fue estadísticamente significativo en los pacientes ASA I. En contraste, solo hubo diferencia estadística en la verificación de los datos de saturación periférica de oxígeno en el momento preoperatorio y de anes- tesia local en los pacientes ASA II (p<=0,04). Al comparar el tiempo de instalación del primer implante (p<=0,03) y al final de la cirugía (p<=0,02), con respecto a la presión sistólica, el ASA II se presentó estadísticamente mayor, mientras que la variable saturación de oxígeno al inicio de la anestesia local en El ASA I fue estadísticamente mayor (p<0,4). Se propone que la sedación intravenosa actúa de forma compensatoria en pacientes con enfermedad sistémica, lo que hace que el comportamiento de ambos grupos sea similar.

Premedication with midazolam in low-risk surgery in children does not reduce postoperative delirium. Prospective cohort study

Introduction: Pediatric postoperative delirium is a frequent complication for which preventive pharmacological measures have been suggested. The use of midazolam as a prophylactic strategy has not yet been thoroughly assessed. Notwithstanding the fact that it is used in pediatric presurgical separation anxiety, its role in delirium is yet to be established. Objective: To quantify the incidence of pediatric postoperative delirium in patients undergoing low risk surgical interventions, exposed to oral midazolam-based premedication and to explore the protective and risk factors associated with the development of delirium. Methods: Prospective, analytical observational study with a cohort design. Children were conveniently selected in accordance with the daily list of surgical procedures in the operating rooms. The inclusion criteria were children between 2 and 10 years old, ASA I-II, undergoing low risk surgeries. Concurrent and longitudinal follow-up was then conducted upon admission to the post-anesthesia care unit (PACU) for the first hour. Results: A total of 518 children were included. The overall incidence of delirium was 14.4 % (95 % CI: 11.4 %-17.5 %). In the subgroup exposed to midazolam, 178 children were analyzed, with an incidence of delirium of 16.2% (95% CI of 10,8 %-21,7). These patients exhibited a higher tendency to delirium with the use of sevoflurane or fentanyl, and/orwhen presenting with severe postoperative pain. Patients exposed to propofol and/or remifentanil showed lower incidences. Conclusions: No reduction in the incidence of emergency pediatric delirium associated with the use of pre-surgical oral midazolam in low risk surgical procedures. Prospective controlled trials and additional research are required to study the effectiveness and safety of this intervention.

Introducción: El delirio pediátrico posoperatorio es una complicación frecuente para la cual se han sugerido medidas farmacológicas de prevención. El uso de midazolam como estrategia profiláctica aún no ha sido suficientemente evaluado. A pesar de que se emplea para la ansiedad de separación pediátrica prequirúrgica, su papel en delirio aún no se ha establecido. Objetivo: Cuantificar la incidencia de delirio pediátrico posoperatorio en pacientes sometidos a cirugías de bajo riesgo quirúrgico, expuestos a premedicación basada en midazolam oral y adicionalmente, explorar los factores protectores y de riesgo asociados a la ocurrencia. Materiales y métodos: Estudio observacional analítico prospectivo con un diseño de cohorte. Se seleccionaron niños por conveniencia de acuerdo con la lista quirúrgica diaria en salas de cirugía. Como criterios de inclusión se tomaron sujetos entre 2 y 10 años de edad, ASA 1-11, sometidos a cirugías de bajo riesgo quirúrgico. Posteriormente se realizó seguimiento concurrente y longitudinal al ingreso a la unidad de recuperación posanestésica (UCPA) durante la primera hora de estancia. Resultados: Se incluyeron 518 niños. La incidencia global de delirio fue del 14,4 % (IC 95 %;11,4 %-17,5 %). En el subgrupo expuesto a midazolam se analizaron 178 niños, quienes presentaron una incidencia de delirio del 16,2 % (IC 95 %;10,8 %-21,7 %). Estos pacientes presentaron una mayor tendencia a delirio con el uso de sevofluorano o fentanilo, y/o cuando presentaron dolor severo posoperatorio. Pacientes con exposición a propofol y/o remifentanilo exhibieron incidencias inferiores. Conclusiones: No se encontró una reducción en la incidencia de delirio pediátrico de emergencia asociada al empleo de midazolam oral prequirúrgico en cirugías de bajo riesgo. Se requieren estudios prospectivos controlados e investigación adicional para el estudio de la efectividad y seguridad de esta intervención.

Comparison between oral midazolam versus oral ketamine plus midazolam as preanesthetic medication in autism spectrum disorder: double-blind randomized clinical trial

Abstract Background: Conventional dental care is often impossible in patients with Autism Spectrum Disorder (ASD). Non-collaborative behaviors, sometimes associated with aggressiveness, are usual justifications for premedication in this population. Thereby, this research focuses on the effects of oral midazolam versus oral ketamine plus midazolam as preanesthetic medication in ASD. Methods: The sample included 64 persons with ASD, aged 2-59 years, scheduled for dental care under general anesthesia. The primary objective of this study was to compare degrees of sedation between two parallel, double-blinded, equally proportional groups randomized to receive oral midazolam (0.5 mg.kg−1, maximum 15 mg) or oral midazolam (0.5 mg.kg−1) associated with oral S(+)-ketamine (3 mg.kg−1, maximum 300 mg). The secondary outcomes were the need of physical stabilization to obtain intravenous line, awakening time, and occurrence of adverse events. Results: According to the dichotomous analysis of sedation level (Ramsay score 1 and 2 versus Ramsay ≥ 3), oral association of S(+)-ketamine and midazolam improved sedation, with increased probability of Ramsay ≥ 3, Relative Risk (RR) = 3.2 (95% Confidence Interval [95% CI] = 1.32 to 7.76) compared to midazolam alone. Combined treatment also made it easier to obtain venous access without physical stabilization, RR = 2.05 (95% CI = 1.14 to 3.68). There were no differences between groups regarding awakening time and the occurrence of adverse events. Conclusion: The association of oral S(+)-ketamine with midazolam provides better preanesthetic sedation rates than midazolam alone and facilitates intravenous line access in patients with autism.

Comparison of intranasal midazolam-fentanyl with dexmedetomidine–fentanyl as pre-medication in the paediatric age group

Background & objectives: Intranasal midazolam-fentanyl is commonly used as pre-medication in paediatric patients, but there is a risk of respiratory depression with this combination. Dexmedetomidine is a drug that preserves respiratory function. The objective of this study was to compare the efficacy of intranasal midazolam-fentanyl and dexmedetomidine-fentanyl in paediatric patients undergoing elective surgeries. Methods: Hundred children in the age group of 3-8 yr of American Society of Anaesthesiologists physical status grade 1 were randomized into two groups- group A received intranasal midazolam (0.2 mg/kg)-fentanyl (2 ?g/kg) and group B received intranasal dexmedetomidine (1 ?g/kg)-fentanyl (2 ?g/kg) 20 min before induction of general anaesthesia. Heart rate and SpO2 were monitored. Sedation score, parental separation and response to intravenous cannulation were seen after 20 min. Children were monitored for 2 h for post-operative analgesia by Oucher’s Facial Pain Scale. Results: Sedation scores were satisfactory in both groups, although children in group A were more sedated than in group B. Parental separation and response to intravenous cannulation were comparable in both the groups. The two groups were also haemodynamically comparable intraoperatively. Post-operative heart rate was also comparable at all-time intervals in both the groups except for heart rate at 100 and 120 min which were more in group A. Group A experienced more post-operative pain as assessed by Oucher’s Facial Pain Scale as compared to group B. Children receiving intranasal dexmedetomidine- fentanyl had better post-operative analgesia as compared to those who received intranasal midazolam-fentanyl. Interpretation & conclusions: Both intranasal midazolam with fentanyl and intranasal dexmedetomidine with fentanyl provided satisfactory sedation. Both groups were comparable in separation reaction and response to intravenous cannulation with better post-operative analgesia in children receiving intranasal dexmedetomidine-fentanyl.

Effects of midazolam modulating cAMP/PKA/CREB pathway on breast cancer cells / 中国现代医生

Objective To investigate the impacts of midazolam on the proliferation,migration and invasion of breast cancer MDA-MD-231 cells and its regulation on cyclic adenosine monophosphate(cAMP)/protein kinase A(PKA)/cAMP response element binding protein(CREB)signaling pathway.Methods MDA-MD-231 cells were cultured in vitro and grouped into control group,midazolam L group,midazolam M group,midazolam H group,and midazolam H+Sp-cAMPS group.Midazolam L group,midazolam M group,midazolam H group were treated with 5μmol/L,10μmol/L,and 20μmol/L of midazolam,respectively,midazolam H+Sp-cAMPS group was added with 20μmol/L of midazolam+10μmol/L of Sp-cAMPS 3-(4,5)-dimethylthiahiazo(-z-y1)-3,5-di-phenytetrazoliumromide(MTT)assay was applied to detect cell proliferation;The migration ability was detected by cell scratch test;Transwell test was applied to determine the invasion ability of cells;Cell apoptosis was detected by flow cytometry;The expression level of cAMP was detected by enzyme-linked immunosorbent assay(ELISA);Western blot was applied to verify the expression of phosphorylated(p-)PKA/PKA,p-CREB/CREB protein.Results Compared with control group,the cells in midazolam L group,midazolam M group,midazolam H group showed apoptosis,the apoptosis rate was obviously increased,the cell proliferation,migration and invasion abilities and the expression levels of cAMP,p-PKA/PKA,p-CREB/CREB proteins were obviously decreased(P<0.05);Compared with midazolam H group,midazolam H+Sp-cAMPS group had good cell growth,obviously reduced apoptosis rate,and obviously increased cell proliferation,migration and invasion abilities,and the expression levels of cAMP,p-PKA/PKA,p-CREB/CREB proteins(P<0.05).Conclusion Midazolam may inhibit the proliferation,migration and invasion of breast cancer cells by inhibiting the activation of cAMP/PKA/CREB signaling pathway.

Comparison of the effects of remimazolam besylate and midazolam on postoperative cognitive function in patients undergoing gynecologic laparoscopic surgery under general anesthesia / 中国医师杂志

Objective:To investigate the effects of remimazolam besylate and midazolam on postoperative cognitive function of patients undergoing gynecologic laparoscopic surgery under general anesthesia.Methods:From May 2019 to January 2021, 120 patients with gynecological laparoscopic surgery under general anesthesia in Haikou Maternal and Child Health Hospital were selected and divided into control group (60 cases) and observation group (60 cases) by random number table. The control group was given 0.05 mg/kg midazolam and 0.50 μg/kg sufentanil and 0.15 mg/kg vecuronium bromide were used for anesthesia induction. Patients in the observation group were given 0.3 mg/kg remimazolam besylate and 0.50 μg /kg sufentanil and 0.15 mg/kg vecuronium were used for anesthesia induction. The levels of hemodynamic indexes before anesthesia (T 0), during anesthesia (T 1), and after intubation (T 2) as well as the levels of postoperative anesthesia recovery indexes were compared between the two groups. The Visual Analogue Scale (VAS) score and Mini-Mental State Examination (MMSE) scores were recorded and compared before surgery, 24 h, 72 h after surgery. The total incidence of adverse reactions after surgery was recorded and compared between the two groups. Results:The heart rate (HR) at T 1 and T 2 in the two groups was higher than that at T 0, the oxygen saturation (SpO 2) at T 1 and T 2 was lower than that at T 0, the mean arterial pressure (MAP) at T 1 was lower than that at T 0, and the MAP at T 2 was higher than that at T 0, with statistically significant difference (all P<0.05); The HR and MAP at T 1 and T 2 in the observation group were lower than those in the control group, and SpO 2 was higher than those in the control group (all P<0.05); The recovery time of spontaneous respiration, eye opening time and extubation time in the observation group were significantly shorter than those in the control group (all P<0.05); The MMSE score at 24 h and 72 h after operation was lower than that before operation, and the VAS score at 24 h was higher than that before operation in both groups (all P<0.05); The MMSE scores in the observation group at 24 h and 72 h after operation were significantly higher than those in the control group (all P<0.05), and there was no significant difference in the VAS scores at 24 h and 72 h after operation between the two groups ( P>0.05); There was no significant difference in the total incidence of adverse reactions between the two groups (all P>0.05). Conclusions:Remimazolam besylate has little effect on cognitive function of patients undergoing gynecologic laparoscopic surgery under general anesthesia, with fast recovery and high safety, which is worthy of clinical promotion.

Role of Nrf2/GPX4 signaling pathway-mediated ferroptosis in midazolam-induced reduction of HIBD in neonatal rats / 中华麻醉学杂志

Objective:To evaluate the role of nuclear factor-erythroid 2-related factor 2 (Nrf2)/glutathione peroxidase-4 (GPX4) signaling pathway-mediated ferroptosis in midazolam-induced reduction of hypoxic-ischemic brain damage (HIBD) in neonatal rats.Methods:Ninety healthy 7-day-old neonatal rats, weighing 16-20 g, were divided into 6 groups ( n=15 each) using the random number table method: sham operation group (Sham group), HIBD group, low-dose midazolam (10 mg/kg) group (group L), medium-dose midazolam (20 mg/kg) group (group M), high-dose midazolam (40 mg/kg) group (group H), and Nrf2 inhibitor ML385 group (group I). The HIBD model was developed by ligating the left carotid artery and exposing to a hypoxic condition for 2 h in anesthetized animals. Starting from 2nd day after developing the model, the corresponding doses of midazolam were intraperitoneally injected in midazolam groups, the equal volume of normal saline was intraperitoneally injected in Sham and HIBD groups, midazolam 40 mg/kg and Nrf2 inhibitor ML385 30 mg/kg were intraperitoneally injected once a day for 8 consecutive days in group I. The rats were weighed and subjected to the Morris water maze test after the end of administration. Blood samples were taken from the abdominal aorta after the end of the Morris water maze test, and then the animals were sacrificed to remove the brain for determination of the concentrations of serum iron, interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α) (by enzyme-linked immunosorbent assay), contents of iron and GSH in hippocampal tissues (by ultraviolet spectrophotometry and micro method), the number of Nrf2/neuronal nuclear antigen (NeuN) and GPX4/NeuN positive cells (by immunofluorescent staining), and expression of Nrf2, GPX4, and 4-hydroxynonaenoic acid (4-HNE) in hippocampal tissues and for microscopic examination of the pathological changes of hippocampal neurons in brain tissues (after HE staining and Nissl staining). Results:Compared with Sham group, the first time to arrival at platform was significantly prolonged, the number of crossing the origional platform was reduced, and the time of staying at the target quadrant was shortened, the iron content in the hippocampal tissues was increased, the content of GSH and the number of Nrf2/NeuN and GPX4/NeuN positive cells were decreased, the expression of Nrf2 and GPX4 was down-regulated, the expression of 4-HNE was up-regulated, the concentrations of serum iron, IL-6 and TNF-α were increased, and the injury to hippocampal neurons was marked in HIBD group ( P<0.05). Compared with HIBD group, the first time to arrival at platform was significantly shortened, the number of crossing the origional platform was increased, and the time of staying at the target quadrant was prolonged, the iron content in the hippocampus tissues was decreased, the content of GSH and the number of Nrf2/NeuN and GPX4/NeuN positive cells were increased, the expression of Nrf2 and GPX4 was up-regulated, the expression of 4-HNE was down-regulated, the concentrations of serum iron, IL-6 and TNF-α were decreased ( P<0.05), and the injury to hippocampal neurons was significantly reduced in H, M and L groups. Compared with group H, the first time to arrival at platform was significantly prolonged, the number of crossing the origional platform was reduced, and the time of staying at the target quadrant was shortened, the iron content in the hippocampus tissue was increased, the content of GSH and the number of Nrf2/NeuN and GPX4/NeuN positive cells were decreased, the expression of Nrf2 and GPX4 was down-regulated, the expression of 4-HNE was up-regulated, the concentrations of serum iron, IL-6 and TNF-α were increased ( P<0.05), and the injury to hippocampal neurons was aggravated in group I. Conclusions:The mechanism by which midazolam reduces HIBD may be related to activation of the Nrf2/GPX4 signaling pathway and inhibition of hippocampal neuronal ferroptosis in neonatal rats.

Effects of midazolam combined with propofol on recovery of patients with laparoscopic cholecystectomy / 药学实践与服务

Objective To explore the effect midazolam combination with propofol on postoperative recovery in patients undergoing laparoscopic cholecystectomy. Methods A total of 162 patients who were admitted to the hospital for laparoscopic cholecystectomy from April 2019 to January 2021 were selected. According to different anesthesia methods, they were divided into control group (midazolam anesthesia) and observation group (midazolam combined with propofol anesthesia), with 81 cases in each group. The stress index levels before and after operation, MoCA scores before operation (T0), 24 h after operation (T1) and 48 h after operation (T2), sleep quality at T0, the first day after operation (T3) and the second day after operation (T4), the perioperative recovery were compared between the two groups. Results The levels of Cor and NE, the recovery time of eyes opening, extubation, orientation, and the incidence of adverse reactions in the observation group were lower than those in the control group (P<0.05). Observation group MMSE score when T1, T2, T3, T4 sleep quality score were higher than control group (P<0.05). Conclusion Midazolam combined with propofol was safe and had good postoperative recovery in patients undergoing laparoscopic cholecystectomy.

Role and mechanism of PKCs in midazolam-induced relaxation of aortic smooth muscle in spontaneously hypertensive rats / 中国药理学通报

Aim To investigate the effect of protein kinase C (PKCs) on midazolam-induced relaxation of aortic smooth muscle in spontaneously hypertensive rats (SHR) and the underlying mechanism. Methods U-sing the isolated vessel tension measurement system, the relaxant effect of midazolam on aortic smooth muscle of SHR and Wistar-Kyoto (WKY) rats was observed. After preincubation with GF109203X (GF, a broad-spectrum inhibitor of PKCs), LY333531 (LY, PKCp2 specific inhibitor) and PKC6 pseudo-substrate inhibitor (PPS), the changes of midazolam-induced relaxation amplitude were observed. Western blot was used to detect the effect of midazolam on the phosphorylation level of PKC [32 in SHR aortic smooth muscle. The effect of midazolam, LY, GF and PPS on the phosphorylation level of the key proteins (CPI-17/ MYPT1/MLC) in calcium sensitization pathway in SHR aortic smooth muscle was also examined. Results Midazolam concentration-dependently relaxed aortic smooth muscle in SHR and WKY. GF significantly inhibited midazolam-induced relaxation amplitude of SHR and WKY aortic smooth muscle. LY and PPS had no significant effect on midazolam-induced relaxation amplitude of WKY aortic smooth muscle. In contrast, LY markedly inhibited midazolam-induced relaxation amplitude of SHR aortic smooth muscle. Midazolam significantly inhibited the phosphorylation level of PKC [32 enhanced by NE in SHR aortic smooth muscle. Midazolam, LY and GF all evidently inhibited the phosphorylation level of the key proteins in calcium sensitization pathway enhanced by NE in SHR aortic smooth muscle. Conclusions Midazolam induces excessive relaxation of SHR aortic smooth muscle by inhibiting calcium sensitization pathway mediated by PKC [32.