Administration Of Midazolam Research Articles

EVALUATION OF ETORPHINE-MEDETOMIDINE-MIDAZOLAMAZAPERONE FOR IMMOBILIZATION IN CAPTIVE PRONGHORN (ANTILOCAPRA AMERICANA).

Etorphine based immobilization protocols are reported to be effective in pronghorn; however, information on cardiorespiratory effects is limited. The objective of this study was to evaluate the efficacy and cardiopulmonary effects of etorphine, medetomidine, midazolam, and azaperone for immobilization in captive pronghorn. Additionally, the effects of endotracheal intubation and manual ventilation on cardiopulmonary variables were assessed. A combination of 5 mg etorphine, 10 mg medetomidine, 2.5 mg midazolam, and 5 mg azaperone was administered by hand or via dart to 10 pronghorn. Five pronghorn were endotracheally intubated once recumbent and manually ventilated. Oxygen at a flow of 6 L/min was supplemented to all animals. Induction and recovery times were recorded, and during recumbency vital parameters and arterial blood samples were collected. Time to lateral recumbency was 3.8 ± 1.25 min. Marked hypoxemia and hypercapnia was observed in both spontaneously breathing and manually ventilated pronghorn. Hypercapnia improved significantly in manually ventilated pronghorn compared to spontaneously breathing animals. All pronghorn recovered rapidly after reversal with 150 mg naltrexone and 30 mg atipamezole. Administration of etorphine, medetomidine, midazolam, and azaperone resulted in excellent chemical immobilization in pronghorn. Significant hypoxemia and hypercapnia occurred and oxygen supplementation, endotracheal intubation, and manual ventilation is recommended.

ICU patient-on-a-chip emulating orchestration of mast cells and cerebral organoids in neuroinflammation

Propofol and midazolam are the current standard of care for prolonged sedation in Intensive Care Units (ICUs). However, the effects and mechanism of these sedatives in brain tissue are unclear. Herein, the development of an ICU patient-on-a-chip platform to elucidate those effects is reported. The humanized neural tissue compartment combines mast cells differentiated from human induced pluripotent stem cells (hiPSCs) with cerebral organoids in a three-dimensional (3D) matrix, which is covered with a membrane populated with human cerebral microvascular endothelial cells (hCMEC/D3) that separates the tissue chamber from the vascular lumen, where sedatives were infused for four days to evaluate neurotoxicity and cell-mediated immune responses. Subsequent to propofol administration, gene expressions of CD40 and TNF-α in mast cells, AIF1 in microglia and GFAP/S100B/OLIG2/MBP in macroglia were elevated, as well as NOS2, CD80, CD40, CD68, IL6 and TNF-α mediated proinflammation is noted in cerebral organoids, which resulted in higher expressions of GJB1, GABA-A and NMDAR1 in the tissue construct of the platform. Besides, midazolam administration stimulated expression of CD40 and CD203c+ reactivated mast cell proliferation and compromised BBB permeability and decreased TEER values with higher barrier disruption, whereas increased populations of CD11b+ microglia, higher expressions of GFAP/DLG4/GJB1 and GABA-A-/NMDAR1- identities, as well as glutamate related neurotoxicity and IL1B, IFNG, IFNA1, IL6 genes mediated proinflammation, resulting in increased apoptotic zones are observed in cerebral organoids. These results suggest that different sedatives cause variations in cell type activation that modulate different pathways related to neuroinflammation and neurotoxicity in the ICU patient-on-chip platform.

NE contribution to rebooting unconsciousness caused by midazolam

The advent of midazolam holds profound implications for modern clinical practice. The hypnotic and sedative effects of midazolam afford it broad clinical applicability. However, the specific mechanisms underlying the modulation of altered consciousness by midazolam remain elusive. Herein, using pharmacology, optogenetics, chemogenetics, fiber photometry, and gene knockdown, this in vivo research revealed the role of locus coeruleus (LC)-ventrolateral preoptic nucleus noradrenergic neural circuit in regulating midazolam-induced altered consciousness. This effect was mediated by α1 adrenergic receptors. Moreover, gamma-aminobutyric acid receptor type A (GABAA-R) represents a mechanistically crucial binding site in the LC for midazolam. These findings will provide novel insights into the neural circuit mechanisms underlying the recovery of consciousness after midazolam administration and will help guide the timing of clinical dosing and propose effective intervention targets for timely recovery from midazolam-induced loss of consciousness.

NE contribution to rebooting unconsciousness caused by midazolam.

The advent of midazolam holds profound implications for modern clinical practice. The hypnotic and sedative effects of midazolam afford it broad clinical applicability. However, the specific mechanisms underlying the modulation of altered consciousness by midazolam remain elusive. Herein, using pharmacology, optogenetics, chemogenetics, fiber photometry, and gene knockdown, this in vivo research revealed the role of locus coeruleus (LC)-ventrolateral preoptic nucleus noradrenergic neural circuit in regulating midazolam-induced altered consciousness. This effect was mediated by α1 adrenergic receptors. Moreover, gamma-aminobutyric acid receptor type A (GABAA-R) represents a mechanistically crucial binding site in the LC for midazolam. These findings will provide novel insights into the neural circuit mechanisms underlying the recovery of consciousness after midazolam administration and will help guide the timing of clinical dosing and propose effective intervention targets for timely recovery from midazolam-induced loss of consciousness.

Clinical Effectiveness and Safety of Midazolam Compared With Lorazepam for Control of Seizures in Adults

What Is the Issue? The emergency treatment of prolonged seizures or status epilepticus is required to be rapid and efficient to prevent permanent brain damage or death. Benzodiazepines, such as midazolam, lorazepam, diazepam, and clonazepam, are established as first-line treatment medications for acute treatments of seizures. Various administration routes of delivery for these drugs have become available, but the comparative clinical effectiveness and safety among administration routes are still unclear. Decision-makers are interested in whether the current use of intramuscular (IM) midazolam for treatment of seizures by paramedics in a prehospital environment can be switched to IV lorazepam as normally used by nurses and physicians in clinic settings. What Did We Do? We identified and summarized the literature on the evidence of the clinical effectiveness and safety of midazolam compared to lorazepam in adults to control seizures. We searched key resources, including journal citation databases, and conducted a focused internet search for relevant evidence published since 2019. One reviewer screened citations for inclusion based on predefined criteria, critically appraised the included studies, and narratively summarized the findings. What Did We Find? We identified 1 systematic review (SR) that included 4 randomized controlled trials (RCTs), only 1 was relevant to this review. This double-blind RCT determined the efficacy of IM midazolam as noninferior to IV lorazepam for treatment of seizures by paramedics in a mixed population of adults (89%) and children (11%). The authors of the SR conducted a subanalysis of a dataset of participant-level data and showed that IM midazolam was as effective and safe as IV lorazepam in adult patients for prehospital seizure cessation. The findings of the adult population were similar to those of the whole randomized population of both adults and children. What Does This Mean? With the shorter time required to administration of midazolam by the IM route compared to administration of lorazepam by the IV route, and the comparable efficacy and safety between the 2 active treatments, the use of IM midazolam may be a better option in the prehospital environment when IV access in patients with seizures is not readily established. Switching of IM midazolam to IV lorazepam for treatment of seizures by paramedics may not be practical.

The effect of intraoperative midazolam on postoperative delirium in older surgical patients: a prospective, multicentre cohort study.

Midazolam is a short-acting benzodiazepine frequently used in the perioperative setting. This study aimed to investigate the potential impact of intraoperative midazolam on postoperative delirium (POD) in older patients undergoing non-cardiac surgery. This study included patients aged ≥ 65 years who received general anaesthesia between April 2020 and April 2022 in multiple hospitals across China. POD occurring within 7 days was assessed using the 3-minute Diagnostic Interview for Confusion Assessment Method (3D-CAM). Univariable and multivariable logistic regression models based on the random effects were used to determine the association between midazolam administration and the occurrence of POD, presented as risk ratio (RR) and 95% confidence intervals (CI). Kaplan-Meier cumulative incidence curve was plotted to compare the distribution of time to POD onset between patients who received midazolam and those who did not. Subgroup analyses based on specific populations were performed to explore the relationship between midazolam and POD. In all, 5,663 patients were included, of whom 723 (12.8%) developed POD. Univariate and multivariable logistic regression analyses based on random effects of different hospitals showed no significant association between midazolam medication and POD among older population (unadjusted RR=0.96, 95% CI: 0.90-1.30, P=0.38; adjusted RR=1.09, 95% CI: 0.91-1.33, P=0.35). Kaplan-Meier curve showed no difference in the distribution of time to POD onset (Hazard ratio [HR]=1.02, 95%CI: 0.88-1.18, P=0.82). The results of subgroup analyses found that intraoperative midazolam treatment was not associated with POD in the specific subgroups of patients. Intraoperative administration of midazolam may not be associated with an increased risk of POD in older patients undergoing non-cardiac surgery.

Vasopressor utilization in septic shock patients receiving propofol versus midazolam

PurposeThe purpose of this study was to evaluate the effect of propofol versus midazolam on vasopressor requirements in patients with septic shock to better guide sedative selection. MethodsThis was a multicenter, retrospective, observational, IRB-approved, non-inferiority cohort study. Included individuals were ≥ 18 years of age, had a diagnosis of septic shock, and exclusive administration of propofol or midazolam for at least 12 h. The primary outcome was maximum increase in vasopressor requirements within the first 12 h following sedative initiation. ResultsFor the primary outcome of maximum increase in norepinephrine equivalents (NEE) within 12 h, propofol was non-inferior to midazolam (0.09 vs. 0.129 μg/kg/min, p = 0.002). No difference was seen between the propofol and midazolam groups for the secondary outcome of maximum increase in NEE within 3 h (0.02 vs 0.04 μg/kg/min, p = 0.208), however, the propofol group had a significantly lower increase within 6 h (0.06 vs 0.086 μg/kg/min, p = 0.043) and 24 h (0.11 vs 0.25 μg/kg/min, p = 0.013). ConclusionIn patients with septic shock, vasopressor requirement increases with propofol were non-inferior to midazolam within the first 12 h.

A Comparison of Ketamine to Midazolam for the Management of Acute Behavioral Disturbance in the Out-of-Hospital Setting

ObjectiveAcute behavioral disturbance is characterized by altered mental status and psychomotor agitation. Pharmacological sedation may be required, risking potential respiratory compromise. We compared the need for emergent airway support following administration of midazolam or ketamine to treat acute behavioral disturbance in the prehospital setting. MethodsIn this retrospective cohort study of patients with acute behavioral disturbance in an urban Emergency Medical Service (EMS) system between 2017-2021, we compared the likelihood of prehospital advanced airway management following administration of midazolam or ketamine. Advanced airway management was defined as prehospital endotracheal intubation or supraglottic airway insertion. ResultsAmong 376 eligible patients, the median age was 35; and 78% were male. The most common etiologies of acute behavioral disturbance were substance use (51%), trauma (18%), and presumed postictal agitation (11%). In all, 162 patients (43%) initially received midazolam and 214 (57%) ketamine. The frequency of advanced airway management was similar between these respective groups (12% [n=19] vs 11% [n=24], difference 0.5%, 95% CI -6.0% to 7.0%). Adjusted for potential confounders, the odds of receiving advanced airway management did not differ between midazolam and ketamine (aOR 1.02, 95% CI 0.44 to 2.38), nor were differences observed in emergency department intubation rates (14% in midazolam recipients, 11% for ketamine) or overall mortality (2% in midazolam recipients, 1% for ketamine). ConclusionIn this cohort study of patients with acute behavioral disturbance, emergent airway support nor other outcomes differed following prehospital treatment with midazolam or ketamine.

γ-Aminobutyric acid type A receptor β1 subunit gene polymorphisms are associated with the sedative and amnesic effects of midazolam

Midazolam is widely used for intravenous sedation. However, wide interindividual variability is seen in the sensitivity to midazolam. The association between genetic factors and interindividual differences in midazolam sensitivity remains unclear. The present study explored the association between common genetic variants and sedative and amnesic effects of midazolam. This prospective study included patients who were scheduled to undergo dental procedures under intravenous sedation. The sedative effect was evaluated using the Ramsay sedation scale 5 min after midazolam (0.05 mg/kg) administration. We employed two parallel approaches in this study: genome-wide approach and candidate gene approach. The γ-aminobutyric acid type A receptor subunit genes were selected as candidate genes. Multivariate linear regression analyses were performed to investigate the association between the Ramsay sedation scale and genetic variants. We also analyzed the association between the presence of anterograde amnesia and genetic variants using multivariate binominal logistic regression analyses. The analyses were adjusted for potential confounding factors. A total of 191 patients were included in the analyses. In the genome-wide association analyses, no significant association was found between the genetic variants and Ramsay scores. In the candidate gene analyses, the rs73247636 (dominant model: β = 0.72 [95% confidence interval, 0.34 to 1.10], P < 0.001) and rs56278524 (dominant model: β = 0.73 [0.37 to 1.10], P < 0.001) polymorphisms of the GABRB1 gene were significantly associated with Ramsay scores. Additionally, the rs73247636 (dominant model: odds ratio [OR] = 8.39 [2.36 to 29.85], P = 0.001) and rs56278524 (dominant model: OR = 15.26 [3.42 to 68.07], P < 0.001) polymorphisms were also significantly associated with the presence of anterograde amnesia. The rs73247636 and rs56278524 single-nucleotide polymorphisms of GABRB1 were associated with the sedative and amnesic effects of midazolam.

Intranasal vs. intramuscular administration of azaperone, midazolam and ketamine in pigs.

To compare the efficacy of intranasal (IN) and intramuscular (IM) administrations of azaperone (3 mg kg-1), midazolam (0. 3 mg kg-1), and ketamine (7 mg kg-1) combination (AMK) in pigs. Study design: Randomized clinical trial. Animals: sixteen adult male pigs, immunocastrated, of mixed lineage. In phase I, these animals were randomly assigned to intranasal (GIN, n = 8) and intramuscular (GIM, n = 8) groups for arterial blood sample collection at 10, 20, 30, 45, 60, and 90 min after AMK administrations for gas and electrolyte analysis. In phase II, performed 1 week after phase I, the 16 pigs were allocated to both groups (GIM, n = 16/GIN, n = 16) and submitted to the same chemical restraint (CR) protocol, with a 96-h interval between administrations. Behavioral parameters (degree of CR, muscle relaxation, loss of postural reflex, and sound stimulus response) and vital parameters (pulse rate, respiratory rate, oxygen saturation, and rectal temperature) were evaluated after recumbency (Trec) and at 5, 15, 30, 45, 60, and 90 min after administrations. In addition, the latency period and duration of CR were determined. Latency to recumbency and duration of CR in GIN were shorter. CR scores did not vary between groups. Muscle relaxation was more intense in GIN at Trec. An initial tachycardia was observed, followed by a reduction in heart rate from T5 to T90 in both treatments (p < 0.05). The respiratory rate was higher at T45, T60, and T90 in GIN compared to baseline. Rectal temperature reduced in GIM from T45 onwards. elevated at T90 in the GIM (p < 0.05) and there was an incidence of mild hypoxemia in 47% of the animals in the GIM. IN administration was as effective as IM administration in promoting safe chemical restraint, with minimal changes in homeostasis, with a shorter duration and latency period.

Comparative Evaluation of Oral and Intranasal Administration of Midazolam as Preanesthetic Medication in Pediatric Dental Patients Treated under General Anesthesia.

Midazolam is commonly used as a preanesthetic medication for behavior management of children. The current study is conducted to find out the effect of midazolam through nasal and oral routes as a premedicament in pediatric patients treated under general anesthesia. The main aims of the study were: to compare the effect of oral syrup and intranasal spray as preanesthetic medication; to record the undesirable side effects of midazolam by both routes. The patients aged 2-6 years of either sex were randomly divided into two equal groups of 30 each-group I: oral; group II: intranasal. The oral and intranasal routes of midazolam were found to be equally effective and provided adequate sedation for easy separation from the parents and cooperation from children during the induction of anesthesia with minimal side effects. Based on the study results, we can conclude that both oral and intranasal midazolam can be used as preanesthetic medication for pediatric dental patients treated under general anesthesia. In pediatric patients, the oral route should be preferred for midazolam premedication in comparison to the intranasal route. Swati, Shah RK, Tandon S, et al. Comparative Evaluation of Oral and Intranasal Administration of Midazolam as Preanesthetic Medication in Pediatric Dental Patients Treated under General Anesthesia. Int J Clin Pediatr Dent 2024;17(8):881-886.

A Comparison of the Use of Propofol versus Midazolam for Pediatric Magnetic Resonance Imaging Sedation: Retrospective Cohort Study.

The aim of the present study was to do a comparison of the recovery profiles and airway-related adverse events of pediatric magnetic resonance imaging (MRI) sedation patients who received propofol alone to those who received midazolam alone. This retrospective cohort study was approved by the Mutah University Ethical Approval Committee (No. 2378). A search of the patients' medical records was performed between September 2021 and April 2022 to identify children aged 4 months-11 years who received propofol or midazolam for MRI sedation. The patients were subdivided into two groups: Those who had propofol alone (propofol group) and those who received midazolam (midazolam group) for pediatric MRI sedation. In propofol group, a 1-2 mg/kg of propofol bolus was given to have a deep sedation (Ramsay Sedation Scale score of 5). Patients in midazolam group received 0.05 mg/kg of midazolam. During the maintenance state of sedation, the patient received 150 µg/kg/min of propofol, and the infusion rate was adjusted in 25 μg/kg/min increments up or down at the discretion of the anesthesiologists to maintain a state of deep sedation. The major targets of this study were recovery profiles (time to awake and time to discharge) and airway-related intervention ratios in pediatric MRI sedation patients. Patient demographics, MRI sedation, and recovery data, including propofol induction dose, airway intervention, and sedation-related adverse events from the pediatric sedation recovery unit were also collected. The mean (standard deviation [SD]) propofol induction dose was higher compared to midazolam group (2.4 [0.7] mg vs. 1.3 [0.5] mg; mean difference, 1.1 mg; P < 0.001). The mean (SD) infusion rate was higher in propofol group compared to midazolam group (161.3 [37.6] μg/min/kg vs. 116.2 [25.6] μg/min/kg; mean difference 45.1 μg/min/kg; P < 0.001). The mean (SD) propofol total dose was higher in propofol group compared to midazolam group (236.3 [102.4] mg vs. 180.7 [80.9] mg; mean difference, 155.4 mg; P < 0.001). The mean (SD) time to awake was longer in midazolam group compared to propofol group (21.2 [5.6] min vs. 23.0 [7.1] min; mean difference, 1.8 min; P < 0.001). The mean (SD) time to discharge was longer in midazolam group compared to propofol group (34.5 [6.9] min vs. 38.6 [9.4] min; mean difference, 4.1 min; 95% confidence interval, 3.0-5.1; P < 0.001). The administration of midazolam during pediatric MRI sedation can decrease the frequency of airway complications without prolonging the clinically significant recovery profile.

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 concentrationsof 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.

Use of Dexmedetomidine, Midazolam, and Ketamine in Prevention of Emergence Agitation in Pediatric Patients Undergoing Surgery Under General Anesthesia

Introduction: Emergence agitation (EA) is a problem that often occurs in pediatric patients during recovery from anesthesia. The cause of EA remained unclear, but the combination of etiologies increases the risk of postoperative agitation. The researchers use various drugs such as ketamine, midazolam, and dexmedetomidine to prevent and treat EA. Objective: This review aims to determine the effectiveness of dexmedetomidine, midazolam, and ketamine in preventing emergence agitation in pediatric patients undergoing surgery under general anesthesia. Method: This literature review is a narrative review that looks at the outcomes of randomized controlled trials (RCT) studies that tested how well dexmedetomidine, midazolam, and ketamine worked at keeping pediatric patients from becoming agitated during emergence. Literature was collected through Google Scholar and PubMed using the keywords Pediatric, Children, Dexmedetomidine, Ketamine, Midazolam, Emergence Agitation, Emergence Delirium, Postoperative Agitation, and Postoperative Delirium and published within the last ten years (2011–2021) in English or Indonesian. The researchers excluded articles that were not available in full, as well as literature reviews. Results: Based on the specified database and keywords identified, there were 695 articles. This literature study included thirteen articles that met the inclusion criteria. Ten articles examined the effectiveness of dexmedetomidine, four reviewed the effectiveness of midazolam, and three examined the effectiveness of ketamine. Conclusion: According to the ten reviewed articles, administering dexmedetomidine or ketamine reduced the incidence of emergence agitation in children. However, the administration of midazolam yielded inconsistent results. To evaluate the optimal dosage, route, and timing of dexmedetomidine, midazolam, and ketamine in preventing EA, further studies are necessary.

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.

Intranasal vs Buccal vs Intramuscular Midazolam for the Home and Emergency Treatment of Acute Seizures in Pediatric Egyptian Patients

Abstract Introduction: Acute convulsions in children are a common emergency worldwide. Benzodiazepines are the recommended first line of treatment. We wished to compare the efficacy, ease of administration and overall satisfaction of midazolam by the buccal, intranasal orintramuscular route in the treatment of acute seizures in Egyptian children both at homes and Emergency room (ER) Methods A prospective, randomized, trial was performed in children aged 1 months to 17 years with acute seizures lasting longer than 5 min. Children were randomly assigned to receive midazolam, 0.2 mg/kg, by the buccal, intranasal or intramuscular route. The primary endpoint was seizure cessation within 10 min of drug administration and no seizure recurrence within 30 minutes. Results There were 196 seizures analysed in home group, 67 patients received midazolam via buccal route, 60 via intranasal, 69 via intramuscular route while 105 patients were recruited from ER 37 patients received buccal midazolam, 34 received intranasal and 34 received intramuscular midazolam. Intramuscular midazolam stopped seizures within 10 min in 94.2 % in home group and 85.3 % in ER group. On the other hand, intranasal midazolam was successful to stop seizures in 93.3% in home group and 88.2 % in ER group within 10 minutes. The buccal route was effective in 91% in home group and 78.4 % in ER group. There were no significant differences in efficacy between all groups. P = 0.763 and P = 0.509 among home and ER groups respectively. Time to seizure cessation was significantly higher in the buccal group 5.11 ± 1.23minutes in home group and 5.91 ± 1.25 in ER group (P = 0.000). Highest overall satisfaction and ease of administration was seen in intranasal group especially among caretakers in home group &amp;gt; 7= 49 (81.7 %) P = 0.002.. Intramuscular midazolam was more preferred by physicians in ERgroup &amp;gt;7=32 (94.1%) (P = 0.001) There were no significant cardio-respiratory events in all groups. Conclusions Our results indicate that there is no clinically important difference between buccal, intranasal and IM routes of administration midazolam. Buccal and intranasal midazolam were safe and effective for treatment of acute seizures in children.

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

BackgroundBenzodiazepines 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). MethodsA 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. ResultsIn 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. ConclusionsIntramuscular, 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.

Pharmacokinetic drug-drug interactions of JBPOS0101 mediated by cytochrome P450 3A4 and UDP-glucuronosyltransferases.

JBPOS0101 is a new antiepileptic drug and is a substrate of UDP-glucuronosyltransferases (UGTs) in invitro test. Invitro experiments showed different results regarding whether JBPOS0101 induces (EC50 136 μM) or inhibits (IC50 95.4-386.5 μM) cytochrome P450 (CYP) 3A4. As co-medication of JBPOS0101 and carbamazepine (CBZ) is expected in clinical settings, drug-drug interactions (DDIs) between them should be determined. This study aimed to investigate pharmacokinetic (PK) interactions of JBPOS0101 influenced by CYP3A4 and UGTs using midazolam (MDZ) and CBZ. A two-cohort, open-label, fixed-sequence study was conducted in healthy Koreans. In cohort A, subjects received MDZ IV alone, and then JBPOS0101 were co-administered with MDZ after oral doses of JBPOS0101 for 7 days. In cohort B, multiple doses of JBPOS0101 and CBZ were administered respectively, and subjects received both together for 7 days. Serial blood samples were collected for PK analysis. When MDZ and JBPOS0101 were co-administered, the systemic exposure of MDZ decreased by 30%. Meanwhile, JBPOS0101 did not significantly changed the PK of CBZ. CBZ decreased the systemic exposure of JBPOS0101 at steady state by 40%, respectively. With IV administration of MDZ, JBPOS0101 acted as a weak inducer of hepatic CYP3A4 and decreased systemic exposure of MDZ. The ability of JBPOS0101 to similarly modulate gut CYP3A4 activity will require further evaluation. Co-administration of multiple doses of JBPOS0101 and CBZ did not significantly alter CBZ pharmacokinetics, but the clinical impact of decreased systemic exposure of JBPOS0101 by CBZ should be further considered.

Successful use of ketamine in reversing the paradoxical reactions to midazolam after failing flumazenil

Midazolam is generally effective and safe to be widely used in the management of seizures, procedural sedation, and anxiolytic. However, paradoxical reactions, though rare, present clinical challenges. Flumazenil is the preferred option for reversing the reactions. Additionally, ketamine, physostigmine, and haloperidol have been successfully used to counteract the adverse effects (AEs). Herein, we report an 11-year-old girl with epilepsy who was brought to the emergency department with a breakthrough seizure. Approximately 10 minutes after a midazolam administration, she developed increased agitation, confusion, uncontrollable crying, and excessive random movements. Despite receiving 4 doses of flumazenil, no improvement was observed. However, the AEs ceased following the administration of ketamine. This report may increase awareness of the uncommon AEs and equip clinicians to effectively handle such occurrences.

Comparison of Changes in Rso2 in Midazolam and Propofol Sedation Post Craniotomy in the Icu of H. Adam Malik Hospital

Introduction: Cerebral oxygen saturation reflects tissue perfusion in the cerebrum. Decreases in cerebral oxygen saturation are linked to longer hospital stays and cognitive impairment. Midazolam and propofol can decrease cerebral blood flow through decreasing the cerebral oxygen metabolic rate. The purpose of this research is to analyze the comparison of changes in cerebral oxygen saturation after midazolam and propofol administration in post-craniotomy patients in the ICU of Haji Adam Malik General Hospital Medan. Subject and Method: This is a randomized control trial study. Patients were divided into, Midazolam group, that given an initial dose of 0.05 mg/kg followed by a maintenance dose of 0.02-0.10 mg/kg/hour and Propofol group that given sedation with a dose of 0.3-3mg/kg/hour, with the target of the 2 groups being a Richmond Agitation-Sedation Scale (RASS) value of 0 to -2. Data analysis using unpaired T test. Results: The results for cerebral regional oxygen saturation and RASS between groups showed significant differences in right and left value (p &lt; 0.001), but there was no significant difference in RASS (p&gt;0.05) between each group at each measurement time. The results of the analysis of cerebral regional oxygen saturation and RASS between times, there was no significant difference in right and left value (p&gt;0.05), but there was a significant difference in RASS (p&lt;0.001) at each measurement time. Based on the results of the analysis carried out, it is known that there is no statistically significant difference in changes in cerebral regional oxygen saturation both right and left in changes in RASS because it is found that all data have p&gt;0.05. Conclusion: There is no change in right and left for cerebral regional oxygen saturation after administration of propofol and midazolam groups with RASS value 0 to -2 in post-craniotomy patients in the ICU of Haji Adam Malik General Hospital Medan