Comparison of remimazolam and midazolam for sedation during colonoscopy in Japanese patients: A propensity score matching analysis.

Objectives: To compare the efficacy and safety of sedation with midazolam and remimazolam for colorectal endoscopy. Methods: This single-center, two-arm, post-hoc analysis of the REM-IICTJP01 study investigated the efficacy and safety of remimazolam for gastrointestinal endoscopic sedation. We enrolled 40 and 208 patients who underwent colonoscopy under remimazolam and midazolam sedation, respectively, during the same period. The primary outcome was the time from the end of the colonoscopy until discharge. The secondary outcomes included the time from the end of the colonoscopy until awakening, dosage, and adverse events. Propensity score matching was employed to eliminate the effect of confounding factors. Results: Thirty-seven patients in each group were matched. After propensity matching, the time to awakening after colonoscopy was 28.0 (13.0-37.0) min in the midazolam group and 0 (0-0) min in the remimazolam group; moreover, the time till discharge was 40.0 (35.0-46.5) min in the midazolam group and 0 (0-5.0) min in the remimazolam group, both of which were significantly shorter in the remimazolam group (p < 0.01). The number of additional doses was 0 (0-0) and 2 (1-3) in the midazolam and remimazolam groups, respectively. The total dose was 2.0 (2.0-3.5) and 6.0 (5.0-7.0) mg in the midazolam and remimazolam groups, respectively. Conclusions: Remimazolam yielded significantly faster times to awakening and discharge safely compared to midazolam.

Comparison of propofol-based sedation and midazolam sedation in pediatric bidirectional endoscopy conducted by pediatric gastroenterologists.

Objectives: The effectiveness and safety of propofol-based sedation and midazolam sedation in pediatric bidirectional endoscopy were compared. Methods: We retrospectively analyzed the cases of pediatric patients (≤15 years old) who had undergone bidirectional endoscopy, esophagogastroduodenoscopy, and colonoscopy by pediatric gastroenterologists. Demographic data, indications, sedatives/dosages, clinical outcomes, endoscopic findings, adverse events, and total patient time requirements (total time in which patients stay in our hospital) were compared in the two sedation groups. Results: Ninety-one children (51 boys, 40 girls, mean age 13 years, range 9-15) treated at our hospital were enrolled. Propofol alone or in combination with midazolam and/or pentazocine was administered to 51 patients (propofol-based sedation group). Midazolam alone or in combination with pentazocine was administered to the other 40 patients (midazolam sedation group). In the propofol group, the following mean doses were used: propofol, 96 mg (range 40-145 mg); midazolam, 4.9 mg (range 3-5 mg); and pentazocine, 7.5 mg. In the midazolam group, the mean doses of midazolam and pentazocine were 6.2 mg (range 4-10 mg) and 15 mg, respectively. All procedures were successfully completed by pediatric gastroenterologists. The total procedure times and endoscopic findings were similar in the two groups, but the median patient time requirement in the propofol group was significantly shorter versus the midazolam group (7.3 h vs. 8.4 h, p < 0.001). No adverse events occurred in either group. Conclusions: Propofol-based sedation in pediatric bidirectional endoscopy was safely and effectively performed by pediatric gastroenterologists, and its patient time requirement was shorter than that for midazolam sedation.

Propofol vs Midazolam As the Initial Sedation Strategy for Mechanically Ventilated Patients: A Single-Center Experience From Saudi Arabia.

Background Propofol and midazolam are the most common sedative agents used in critical settings. Propofol and midazolam might have different mortality rates after sedation administration. Some studies mention that propofol is associated with a lower mortality rate than midazolam in mechanically ventilated patients, but other studies have contradicting results. This study aims to compare the 28-day mortality of propofol versus midazolam for patients undergoing mechanical ventilation in the National Guard Hospital Health Affairs (NGHA)-Western Region (WR). Methods A retrospective chart review was conducted at (NGHA-WR) from March 2016 to July 2022. The inclusion criteria were those mechanically ventilated patients aged 18 years or older who were admitted to ICU, where they were given either propofol or midazolam as the initial sedative agent. Those who signed DNR (Do Not Resuscitate) or were contraindicated to sedation, such as allergy, were excluded from the study. Data were retrospectively retrieved and obtained from the Hospital Information System (HIS-BestCare, Saudi-Korean Health Informatics Company, Riyadh, Saudi Arabia) and the Office of Data Intelligence. Results There is a significant difference between the type of sedation and the 28-day mortality rate. Midazolam was associated with higher rates of mortality - 104 (47.93%) when compared to propofol - three (14.29%). Also, patients who used midazolam had longer durations of ICU stay compared to propofol, with a mean number of 19.23 days vs 7.55 days, respectively. Conclusion There is a significant difference regarding the 28-day mortality between patients who were given propofol or midazolam as an initial sedative agent for mechanical ventilation ≥ 24 hours. Moreover, the use of propofol is associated with fewer days of being intubated or being in ICU when compared to midazolam.

Alterations in GABAA receptor-mediated inhibition triggered by status epilepticus and their role in epileptogenesis and increased anxiety.

The triggers of status epilepticus (SE) in non-epileptic patients can vary widely, from idiopathic causes to exposure to chemoconvulsants. Regardless of its etiology, prolonged SE can cause significant brain damage, commonly resulting in the development of epilepsy, which is often accompanied by increased anxiety. GABAA receptor (GABAAR)-mediated inhibition has a central role among the mechanisms underlying brain damage and the ensuing epilepsy and anxiety. During SE, calcium influx primarily via ionotropic glutamate receptors activates signaling cascades which trigger a rapid internalization of synaptic GABAARs; this weakens inhibition, exacerbating seizures and excitotoxicity. GABAergic interneurons are more susceptible to excitotoxic death than principal neurons. During the latent period of epileptogenesis, the aberrant reorganization in synaptic interactions that follow interneuronal loss in injured brain regions, leads to the formation of hyperexcitable, seizurogenic neuronal circuits, along with disturbances in brain oscillatory rhythms. Reduction in the spontaneous, rhythmic "bursts" of IPSCs in basolateral amygdala neurons is likely to play a central role in anxiogenesis. Protecting interneurons during SE is key to preventing both epilepsy and anxiety. Antiglutamatergic treatments, including antagonism of calcium-permeable AMPA receptors, can be expected to control seizures and reduce excitotoxicity not only by directly suppressing hyperexcitation, but also by counteracting the internalization of synaptic GABAARs. Benzodiazepines, as delayed treatment of SE, have low efficacy due to the reduction and dispersion of their targets (the synaptic GABAARs), but also because themselves contribute to further reduction of available GABAARs at the synapse; furthermore, benzodiazepines may be completely ineffective in the immature brain.

Effectiveness of pharmacological procedural sedation in children with autism spectrum disorder: A systematic review and meta-analysis.

AIM: Management of primary healthcare and routine minor procedures for children with autism spectrum disorder (ASD) can be challenging; therefore, when behavioural strategies fail, sedative medications are often employed. We evaluated the effectiveness of the current pharmacological strategies for managing children with ASD. METHODS: We performed a systematic review and meta-analysis of the current approaches for procedural sedation in children with ASD. RESULTS: Twenty studies met inclusion criteria. Dexmedetomidine, midazolam, propofol and chloral hydrate were the most efficient agents for successful procedures, while propofol had the highest number of adverse events. The most frequently used agents were dexmedetomidine and midazolam or a combination of the two, and the effectiveness of dexmedetomidine plus midazolam was superior to dexmedetomidine alone. CONCLUSION: Multiple effective drug regimens exist for procedural sedation in children with ASD. These results could support the development of specific guidelines for procedural sedation in children with ASD.

Quantium Consciousness Index and Quantium Noxious Index in Ketamine Subdose Administration Compared with Fentanyl and Midazolam in Postoperative ICU Patients: A Prospective, Observational Study.

Aims and background: In postoperative patients in the intensive care units (ICUs), not only analgesics are needed but also sedation so that the patient can remain calm during treatment, especially patients with mechanical ventilation. By using the measurement parameters of the quantum consciousness index (qCON) and quantum noxious index (qNOX) in measuring the depth of sedation and adequacy of analgesics, the use of subdose ketamine instead of fentanyl and midazolam as sedative, analgesic agents can be performed as a new alternative to nociceptive monitoring methods with more objective results. This study aims to obtain results of comparing qCON and qNOX in postoperative patients by administering subdose ketamine compared with a combination of fentanyl and midazolam in RSUP Haji Adam Malik Medan. Materials and methods: A randomized clinical trial with a double-blind approach has been used in this study. A total of 44 experimental samples were gathered and randomly split into two groups after meeting the criteria for inclusion. Group A administered a ketamine subdose, whereas Group B administered a mixture of fentanyl and midazolam. The research data obtained were tested using Statistical Product and Science Service (SPSS). Results: There were differences in the median, minimum, and maximum values of qCON and qNOX in the groups given subdose ketamine and fentanyl and midazolam, but these were not statistically significant (p > 0.05) at T0, T1, and T2. Conclusion: Administering a subdose of ketamine can provide sedation and analgesia comparable to fentanyl and midazolam. How to cite this article: Masharto AR, Lubis AP, Bangun CG, Wahyuni AS. Quantium Consciousness Index and Quantium Noxious Index in Ketamine Subdose Administration Compared with Fentanyl and Midazolam in Postoperative ICU Patients: A Prospective, Observational Study. Indian J Crit Care Med 2024;28(6):581-586.

Four-year review of safe and effective procedural sedation in neonates and young infants.

Objectives: Newborns and small infants are unable to cooperate actively during diagnostic procedures; therefore, sedation is often employee to maintain immobilization and obtain high-quality images. However, these procedures are often indicated in sick, vulnerable, or hemodynamically unstable neonates and young infants, which raises the associated risks of sedation. This study summarizes our 4-year of experience with safe and effective procedural sedation in this vulnerable population. Study design: This retrospective study analyzed data on neonates and young infants who underwent non-painful diagnostic procedures from December 2019 to November 2023. Patients were categorized into the neonate (aged≦ 28 days) and the young infant (29 days ≦ aged ≦ 90 days) groups. Results: Non-pharmacological strategies, including sleeping naturally, swaddling/facilitated tucking, non-nutritive sucking, and skin-to-skin care, can achieve a success rate for sedation about 98.4%. In terms of pharmacological methods, our institution primarily utilizes chloral hydrate for procedural sedation in neonates and young infants undergoing non-painful diagnostic procedures. Midazolam serves as an alternative sedative. Chloral hydrate alone demonstrated a 92.5% success rate on the first attempt, compared to midazolam alone, with an 85.11% success rate. Neonates experienced a higher incidence of adverse events during sedation compared to young infants. Conclusion: This study reviews our 4-year experience with procedural sedation in neonates and young infants. Chloral hydrate demonstrated a high degree of safety and efficacy in this population. However, supervision by skilled medical personnel and extended observation is required. In our institution, the experience with midazolam is limited in this population, and further research is warranted to establish its safety and efficacy. Non-pharmacological strategies can achieve an acceptable rate of sedation success, which can be used based on patient's tolerance.

Effect of Alleviating Preoperative Anxiety on Gastrointestinal Function Recovery After Laparoscopic High Ligation of the Hernia Sac in Children with Indirect Inguinal Hernia.

Purpose: Anxiety and depression can affect the physiology of the gastrointestinal tract through the brain-gut axis, causing gastrointestinal dysfunction, which is mainly manifested as indigestion, diarrhoea, constipation, or abdominal pain. Preoperative anxiety arises in children due to separation from parents, fear of unfamiliar surroundings and anaesthesia and surgical procedures.To discuss the effect of alleviating preoperative anxiety on postoperative recovery of gastrointestinal function in children with indirect inguinal hernia after laparoscopic high ligation of the hernia sac. Patients and Methods: 90 children with laparoscopic high ligation of the herniated sac in oblique inguinal hernia were randomly divided into control group (Group C) and experimental group (Group M). The Group M was given midazolam oral solution 0.5mg/kg (maximum dose 20mg), and The Group C was given 5% glucose solution with the same dose.Primary outcome was the time to first postoperative defecation and I-FEED scores.The secondary outcomes included mYPAS-SF scores; child sedation scores; child-parent separation scores; parental STAI scores;PHBQ scores;FLACC scores, operative time, and fluid input and surgeon job satisfaction. Results: Compared with Group C, there was a shorter time to first postoperative defecation (P < 0.05), and lower I-FEED scores on postoperative day 1 (P < 0.05). The mYPAS-SF scores, which were significantly different in Group M at T1, T2, and T3 (P < 0.05), parental STAI scores at S1, child sedation scores and child-parent separation scores in T1, and surgeon job satisfaction between the two groups were significantly different (P < 0.05). There were no statistically significant differences in I-FEED scores on days 2 and 3, PHBQ scores, FLACC scores, operative time, and fluid input between the two groups of children (P > 0.05). Conclusion: Preoperative application of midazolam oral solution to relieve preoperative anxiety helps to promote the recovery of postoperative gastrointestinal function in children with indirect inguinal hernia and increases the surgeon job satisfaction.

Comparison of Fentanyl With Midazolam As Adjuvants to Levobupivacaine in Spinal Anesthesia for Cesarean Sections: A Randomized Controlled Trial.

Background and objectives Spinal anesthesia stands as a cornerstone for patients undergoing lower segment cesarean section (LSCS), offering advantages like faster onset and high block density. Levobupivacaine, known for its high potency and long-acting nature, has a slower onset. The safety of intrathecal fentanyl or midazolam is evaluated as an adjuvant to levobupivacaine in parturients. This study aims to compare the duration of postoperative analgesia provided by fentanyl or midazolam added to 0.5% hyperbaric levobupivacaine in elective cesarean sections. Secondary objectives include evaluating the onset and duration of sensory and motor blockade and the incidence of nausea and vomiting. Identifying the more effective adjuvant will help optimize spinal anesthesia protocols, improve postoperative outcomes, and enhance patient comfort and recovery. Methods This study was conducted at SRM Medical College Hospital and Research Centre, Chennai, India, over six months (May 1, 2023, to October 1, 2023). A total of 90 patients undergoing elective LSCS received spinal anesthesia in a prospective randomized double-blinded controlled trial. Patients were allocated to three groups: Group A received levobupivacaine with fentanyl, Group B received levobupivacaine with midazolam, and Group C received levobupivacaine with normal saline. Block characteristics, postoperative analgesia, hemodynamic stability, and complications were assessed. Assessments were conducted at specified time points: intraoperatively, every five minutes for the first 30 minutes, every 10 minutes for the next hour, every two hours for six hours, and every four hours up to 24 hours postoperatively. Statistical analysis utilized one-way analysis of variance (ANOVA). Results Group B (levobupivacaine with midazolam) exhibited a shorter time to sensory block onset (88 seconds) compared to Groups A and C (both 145 seconds) (p < 0.001). Group A (levobupivacaine with fentanyl) showed a shorter time to maximum motor block (p = 0.045) than Groups B and C. The sensory block duration was significantly longer in Group A (127.5 minutes) compared to Group B (60 minutes) and Group C (69 minutes) (p < 0.001). Motor block duration was also prolonged in Group A (251 minutes) compared to Group B (147 minutes) and Group C (177 minutes) (p = 0.045). The first analgesic requirement was delayed in Group A (248 minutes), whereas Groups B (115 minutes) and C (90 minutes) (p < 0.001) required more frequent analgesia. Group A experienced a higher incidence of postoperative nausea and vomiting. Conclusion Midazolam accelerated sensory block onset, while fentanyl prolonged anesthesia duration without significantly affecting motor block. Fentanyl delayed the first analgesic requirement, whereas midazolam reduced postoperative nausea, vomiting, and shivering.

Intranasal atomized dexmedetomidine alone or in combination with ketamine or midazolam to sedate healthy dogs.

A prospective, randomized, blinded experiment was conducted to compare the effects of intranasal (IN) dexmedetomidine (Dex, 10µg/kg; n=12) alone or combined with midazolam (DexM, 0.3mg/kg; n=12) or ketamine (DexK, 2mg/kg; n=12) in healthy dogs. Ease of administration (EA1), total administration time (TAT), time for first (TA1) and second nostril administration (TA2), and adverse events during atomization were recorded. Two days later, EA2 was assessed by IN atomization of injectable water as an additional outcome variable. Onset of sedation was evaluated, along with behavioral scores and physiological parameters from T0 (baseline) to T120. Statistical analyses included Chi-square, one-way ANOVA or Kruskal-Wallis, repeated measures or Friedman's ANOVA, and Wilcoxon's tests. Significance was p≤0.05. Onset of sedation was 12.9 ± 4.1, 18.2 ± 7.5, and 9.9 ± 4.3mins (mean ± SD) for Dex, DexM, and DexK, respectively. Onset was shorter in DexK compared to DexM (p=0.002), explaining the lower behavioral scores in DexM at T15. All dogs in Dex and DexK reached adequate sedation, with peak sedation occurring at T30, while some dogs in DexM never reached adequate sedation and this group peaked at T45. Adverse events such as saliva drooling and pawing at the nose were significantly higher in DexM and DexK, explaining their differences in TA2, TAT, and EA1 comparing to Dex. EA2 was also higher in Dex compared to DexM and DexK. In conclusion, Dex was better tolerated in dogs and DexK showed faster and more profound sedative effects. Due to paradoxical excitement, unpredictable sedation, and nasal irritation, DexM is not recommended.

Perioperative use of immersive head-mounted virtual reality display enhances patient satisfaction in great saphenous vein surgery: a single-center clinical observation study.

OBJECTIVE: To explore the application effect of head-mounted virtual reality display immersive experience in improving the perioperative satisfaction of patients undergoing great saphenous vein surgery. METHODS: A total of 158 patients undergoing saphenous vein surgery at the First Affiliated Hospital, Jiangxi Medical College, Nanchang University from January 2020 to January 2023 were randomly divided into an observation group and a control group in a 1:1 ratio, with 79 cases in each group. The observation group received head-mounted display virtual reality immersive experience, whereas the control group received midazolam. The study compared the perioperative satisfaction, changes in preoperative and postoperative anxiety and depression scores, intraoperative blood pressure and heart rate, postoperative visual analog scale (VAS) score, and the incidence of postoperative nausea and vomiting between the two groups. Additionally, the satisfaction of patients, anesthesiologists, and chief surgeons was compared. RESULTS: All surgeries were completed successfully. Patients in the observation group exhibited higher perioperative satisfaction compared to those in the control group (P<0.001). There were no significant differences in anxiety or depression scores between the two groups before surgery (P>0.05). However, both groups showed a reduction in anxiety and depression scores postoperatively, with the observation group demonstrating lower scores than the control group (both P<0.05). The observation group also had lower intraoperative blood pressure, heart rate, postoperative VAS scores, and incidence of nausea and vomiting compared to the control group (all P<0.05). Furthermore, the satisfaction levels of the anesthesiologists and chief surgeons were higher in the observation group than in the control group (P=0.043, 0.012). CONCLUSION: Head-mounted display virtual reality immersive experience can enhance perioperative satisfaction among patients undergoing great saphenous vein surgery, reduce anxiety and depression scores, and contribute to the stabilization of hemodynamics during surgery, thereby decreasing postoperative nausea and vomiting.

Challenges of status epilepticus management in a resource-limited setting: A review.

Status epilepticus (SE) is a life-threatening neurological condition with significant mortality. Rapid management is essential to minimize the mortality and disability of SE. Two recent trials provided evidence to guide SE management in early and established stages. The Rapid Anticonvulsant Medication Prior To Arrival Trial (RAMPART, 2011) showed that intramuscular midazolam is a better alternative for early convulsive SE in prehospital settings. The Established Status Epilepticus Treatment Trial (ESETT, 2020) supported the use of sodium valproate and levetiracetam as second-line treatment for its efficacy and shorter administration time. However, there are challenges to revising the status epilepticus management in resource-limited settings, in pre-hospital, first- and second-line treatment, as well as management of refractory and super-refractory SE. These challenges included restrictions or lack of training in the administration of benzodiazepine in the prehospital setting, limited availability and accessibility of newer antiseizure medications (ASMs) in emergency departments and smaller hospitals, and low clinicians' awareness of the latest evidence. A collaborative effort to educate, improve awareness, and make certain ASMs more readily available is recommended to achieve a better clinical outcome in SE.

Advantages of remimazolam for sedation in impacted tooth extraction.

OBJECTIVES: This study aims to compare the sedative effects of remimazolam and midazolam during impacted tooth extraction to provide a comfortable sedation treatment for patients with dental anxiety. METHODS: A prospective randomized controlled trial was conducted, in which 60 patients undergoing intravenous sedation for mandibular impacted third molar extraction were evenly divided into either the remimazolam or midazolam group. Prior to receiving a nerve blocker, the patients were sedated with remimazolam or midazolam. Various parameters were recorded and analyzed, including onset time, awakening time, recovery time, modified dental anxiety scale (MDAS) scores before and after surgery, patient-doctor satisfaction levels, postoperative side effects within 24 hours, heart rate (HR), and mean arterial pressure (MAP) at different time points. RESULTS: Compared with the midazolam group, patients in the remimazolam group demonstrated significantly shorter onset, awakening, and recovery times as well as lower postoperative MDAS scores and higher levels of patient-doctor satisfaction. Fewer postoperative side effects were reported in the remimazolam group, although the differences were not statistically significant. CONCLUSIONS: The use of remimazolam demonstrates faster onset and recovery, superior efficacy in reducing dental anxiety, and enhanced satisfaction among patients and doctors, thereby presenting distinct advantages for sedation treatment for patients with dental anxiety.

Midazolam Indications and Dosing in Palliative Medicine: Results from a Multinational Survey.

Despite sparse evidence and limited guidance on indications, use, and dosing, midazolam is widely used in palliative care. We aimed to describe and compare the use of midazolam in three different countries to improve clinical practice in palliative care. We performed an online survey among palliative care physicians in Norway, Denmark, and the United Kingdom (UK). The focus was indications, dosing, administration, and concomitant drugs. A web-based questionnaire was distributed to members of the respective national palliative medicine associations. The total response rate was 9.4%. Practices in the UK, Norway, and Denmark were overall similar regarding the indications of midazolam for anxiety, dyspnoea, and pain treatment in combination with opioids. However, physicians in the UK used a higher starting dose for anxiety, dyspnoea, and pain treatment compared to Norway and Denmark, as well as a higher maximum dose. Danish physicians preferred, to a higher degree, on-demand midazolam administration. Despite practice similarities in the UK, Norway, and Denmark, differences exist for midazolam dosing and administration in palliative medicine. We demonstrated a lack of consensus on how midazolam should be used in palliative care, setting the stage for future studies on the topic.

Potential for Drug Repositioning of Midazolam as an Inhibitor of Inflammatory Bone Resorption.

Drug repositioning is a method for exploring new effects of existing drugs, the safety and pharmacokinetics of which have been confirmed in humans. Here, we demonstrate the potential drug repositioning of midazolam (MDZ), which is used for intravenous sedation, as an inhibitor of inflammatory bone resorption. We cultured a mouse macrophage-like cell line with or without MDZ and evaluated its effects on the induction of differentiation of these cells into osteoclasts. For in vivo investigations, we administered lipopolysaccharide (LPS) together with MDZ (LPS+MDZ) to the parietal region of mice and evaluated the results based on the percentage of bone resorption and calvaria volume. Furthermore, we examined the effects of MDZ on the production of reactive oxygen species (ROS) in cells and on its signaling pathway. MDZ inhibited osteoclast differentiation and bone resorption activity. In animal studies, the LPS+MDZ group showed a decreasing trend associated with the rate of bone resorption. In addition, the bone matrix volume in the LPS+MDZ group was slightly higher than in the LPS only group. MDZ inhibited osteoclast differentiation by decreasing ROS production and thereby negatively regulating the p38 mitogen-activated protein kinase pathway. Thus, we propose that MDZ could potentially be used for treating inflammatory bone resorption, for example, in periodontal disease.

An open-label study to explore the optimal design of CYP3A drug-drug interaction clinical trials in healthy Chinese people.

A drug-drug interaction (DDI) trial of cytochrome P450 3A (CYP3A) is a necessary part of early-phase trials of drugs mainly metabolized by this enzyme, but CYP3A DDI clinical trials do not have a standard design, especially for Chinese people. We aimed to offer specific recommendations for CYP3A DDI clinical trial design. This was an open, three-cycle, self-controlled study. Healthy subjects were given different administration strategies of CYP3A4 perpetrators. In each cycle, blood samples were collected before and within 24 h after the administration of midazolam, the CYP3A indicator substrate. The plasma concentrations of midazolam and 1-hydroxymidazolam was obtained using liquid chromatography tandem mass spectrometry assay. For CYP3A inhibition, itraconazole exposure with a loading dose could increase the exposure of midazolam by 3.21-fold based on maximum plasma concentration (Cmax), 8.37-fold based on area under the curve Pharmacology Research & Perspectives for review only from zero to the time point (AUC0-t), and 11.22-fold based on area under the curve from zero to infinity (AUC0-∞). The data were similar for itraconazole pretreatment without a loading dose. For CYP3A induction, the exposure of rifampin for 7 days decreased the plasma concentration of midazolam ~0.27-fold based on Cmax, ~0.18-fold based on AUC0-t, and ~0.18-fold based on AUC0-∞. Midazolam exposure did not significantly change when the pretreatment of rifampin increased to 14 days. This study showed that itraconazole pretreatment for 3 days without a loading dose was enough for CYP3A inhibition, and pretreatment with rifampin for 7 days could induce near-maximal CYP3A levels.

An analysis of oxidative stress indices and clinical parameters in budgerigars (Melopsittacus undulatus) treated with medetomidine-ketamine and midazolam-ketamine.

Various companion birds, including budgerigars, are anesthetized with injectable anesthesia. The current study aimed to evaluate oxidative stress indices including malondialdehyde (MDA), total antioxidant capacity (TAC), total oxidant status (TOS), and oxidative stress index (OSI) along with clinical parameters such as the time required to induce, maintain and recover from medetomidine-ketamine anesthesia and midazolam-ketamine anesthesia in budgerigars. Among 20 mature and healthy budgerigars, three groups were assigned as follows: Control (n = 4) to determine baseline oxidative stress indices medetomidine + ketamine (n = 8) anesthetized by intramuscular injections of medetomidine (0.04 mg kg-1) and ketamine (30.00 mg kg-1) in the pectoral muscles, midazolam + ketamine (n = 8) anesthetized by intramuscular injections of midazolam (1.00 mg kg-1) and ketamine (50.00 mg kg-1). Half of birds (n = 4) in the second and third groups were euthanized by cervical dislocation 1 hr after anesthesia induction, blood samples were collected directly from the heart, and sera were extracted. Additionally, the remaining birds were euthanized 24 hr later, and their serum was analyzed for oxidative stress indices. Clinical parameters were recorded during the study. Compared to the medetomidine + ketamine group, the midazolam + ketamine group experienced shorter induction, anesthetic, and recovery times. Administering medetomidine and ketamine elevated TOS levels compared with midazolam + ketamine. No significant difference was found between the test groups for TAC, MDA, or OSI. Therefore, the midazolam + ketamine regimen appears superior to medetomidine + ketamine when performing minor surgeries on budgerigars.

Intranasal Versus Buccal Versus Intramuscular Midazolam for the Home and Emergency Treatment of Acute Seizures in Pediatric Patients: A Randomized Controlled Trial.

BACKGROUND: Benzodiazepines are the recommended first-line treatment of acute seizures. We wished to compare the efficacy, side effects, and satisfaction after midazolam administration by the buccal, intranasal, or intramuscular route in the treatment of acute seizures in children at homes and in emergency room (ER). METHODS: A prospective, randomized, controlled trial was performed in children aged one month to 17 years with acute seizures lasting longer than five minutes. The primary end point was seizure cessation within 10 minutes of drug administration and no seizure recurrence within 30 minutes. RESULTS: In the home group, 67 patients received midazolam via buccal route, 60 via intranasal route, and 69 via intramuscular route, whereas in the ER group, 37 patients received buccal, 34 received intranasal, and 34 received intramuscular midazolam. The primary end point was achieved in 94.2% and 85.3% after intramuscular midazolam in the home and ER groups, respectively. The intranasal midazolam was successful in stopping seizures in 93.3% in the home group and 88.2% in the ER group. The buccal route was effective in 91% in the home group and 78.4% in the ER group. There were no significant differences in efficacy between all groups (P = 0.763 and P = 0.509) among the home and ER groups, respectively. There were no significant cardiorespiratory events in all groups. CONCLUSIONS: Intramuscular, intranasal, and buccal doses of midazolam resolved most seizures in prehospital and emergency settings. Our results indicate that there is no statistically significant difference detected between different routes of midazolam. Intranasal route showed the highest satisfaction rate among caregivers.

Total intravenous anesthesia with Ketofol in rabbits: a comparison of the effects of constant rate infusion of midazolam, fentanyl or dexmedetomidine.

BACKGROUND: When inhalant anesthetic equipment is not available or during upper airway surgery, intravenous infusion of one or more drugs are commonly used to induce and/or maintain general anesthesia. Total intravenous anesthesia (TIVA) does not require endotracheal intubation, which may be more difficult to achieve in rabbits. A range of different injectable drug combinations have been used as continuous infusion rate in animals. Recently, a combination of ketamine and propofol (ketofol) has been used for TIVA in both human patients and animals. The purpose of this prospective, blinded, randomized, crossover study was to evaluate anesthetic and cardiopulmonary effects of ketofol total intravenous anesthesia (TIVA) in combination with constant rate infusion (CRI) of midazolam, fentanyl or dexmedetomidine in eight New Zealand White rabbits. Following IV induction with ketofol and endotracheal intubation, anesthesia was maintained with ketofol infusion in combination with CRIs of midazolam (loading dose [LD]: 0.3 mg/kg; CRI: 0.3 mg/kg/hr; KPM), fentanyl (LD: 6 µg/kg; CRI: 6 µg/kg/hr; KPF) or dexmedetomidine (LD: 3 µg/kg; CRI: 3 µg/kg/hr; KPD). Rabbits in the control treatment (KPS) were administered the same volume of saline for LD and CRI. Ketofol infusion rate (initially 0.6 mg kg- 1 minute- 1 [0.3 mg kg- 1 minute- 1 of each drug]) was adjusted to suppress the pedal withdrawal reflex. Ketofol dose and physiologic variables were recorded every 5 min. RESULTS: Ketofol induction doses were 14.9 ± 1.8 (KPM), 15.0 ± 1.9 (KPF), 15.5 ± 2.4 (KPD) and 14.7 ± 3.4 (KPS) mg kg- 1 and did not differ among treatments (p > 0.05). Ketofol infusion rate decreased significantly in rabbits in treatments KPM and KPD as compared with saline. Ketofol maintenance dose in rabbits in treatments KPM (1.0 ± 0.1 mg/kg/min) and KPD (1.0 ± 0.1 mg/kg/min) was significantly lower as compared to KPS (1.3 ± 0.1 mg/kg/min) treatment (p < 0.05). Ketofol maintenance dose did not differ significantly between treatments KPF (1.1 ± 0.3 mg/kg/min) and KPS (1.3 ± 0.1 mg/kg/min). Cardiovascular variables remained at clinically acceptable values but ketofol infusion in combination with fentanyl CRI was associated with severe respiratory depression. CONCLUSIONS: At the studied doses, CRIs of midazolam and dexmedetomidine, but not fentanyl, produced ketofol-sparing effect in rabbits. Mechanical ventilation should be considered during ketofol anesthesia, particularly when fentanyl CRI is used.

Optimising the oral midazolam dose for premedication in people with intellectual disabilities and/or autism spectrum disorder.

BACKGROUND: In people with intellectual disabilities and/or autism spectrum disorder, oral midazolam (OM) is very effective as premedication for facilitating medical treatment. In this retrospective study, we investigated the optimal dosage of OM for premedication. METHODS: Patients with intellectual disability and/or autism spectrum disorder who were given OM as a premedication were selected from anaesthesia records. The primary outcome variable was the dose of OM (mg/kg) required to produce an adequate sedation. RESULTS: The mean OM dose required was 0.32 ± 0.10 mg/kg. The required OM dose decreased significantly as age and weight increased, and age and weight were also shown to be significantly associated with the dose of OM in the multivariate linear regression analysis. CONCLUSION: The dosage of OM to achieve adequate sedation should decrease as the patient ages. Furthermore, adequate sedation can be achieved with even lower doses of OM in obese people.