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International Journal of Surgery... Jul 2023Severe dental phobia or failure to cooperate with treatment are very common in outpatient pediatric dentistry. Personalized and appropriate noninvasive anesthesia... (Clinical Trial)
Clinical Trial
BACKGROUND
Severe dental phobia or failure to cooperate with treatment are very common in outpatient pediatric dentistry. Personalized and appropriate noninvasive anesthesia methods can save medical expenses, improve treatment efficiency, reduce the anxiety of children, and improve the satisfaction of nursing staff. Currently, there is little conclusive evidence for noninvasive moderate sedation strategies in pediatric dental surgery.
MATERIALS AND METHODS
The trial was conducted from May 2022 to September 2022. Each child was first given midazolam oral solution 0.5 mg·kg -1 , and when the Modified Observer's Assessment of Alertness and Sedation score reached 4, a biased coin design up-down method was used to adjust the dose of esketamine. The primary outcome was the ED 95 and 95% CI of intranasal esketamine hydrochloride with midazolam 0.5 mg·kg -1 . Secondary outcomes included the onset time of sedation, treatment and awakening times, and the incidence of adverse events.
RESULTS
A total of 60 children were enrolled; 53 children were successfully sedated but 7 were not. The ED 95 of intranasal esketamine with 0.5 mg·kg -1 midazolam oral liquid for the treatment of dental caries was 1.99 mg·kg -1 (95% CI 1.95-2.01 mg·kg -1 ). The mean onset time of sedation for all patients was 43.7±6.9 min. 15.0 (10-24.0) min for examination and 89.4±19.5 min for awakening. The incidence of intraoperative nausea and vomiting was 8.3%. Adverse reactions such as transient hypertension and tachycardia occurred during the operations.
CONCLUSION
The ED 95 of intranasal esketamine with 0.5 mg·kg -1 midazolam oral liquid for the outpatient pediatric dentistry procedure under moderate sedation was 1.99 mg·kg -1 . For children aged 2-6 years with dental anxiety who require dental surgery, anesthesiologists may consider using midazolam oral solution combined with esketamine nasal drops for noninvasive sedation after a preoperative anxiety scale evaluation.
Topics: Child; Humans; Anesthesia; Dental Caries; Hypnotics and Sedatives; Midazolam; Outpatients; Prospective Studies
PubMed: 37288546
DOI: 10.1097/JS9.0000000000000340 -
The British Journal of Psychiatry : the... Dec 2023Prior trials suggest that intravenous racemic ketamine is a highly effective for treatment-resistant depression (TRD), but phase 3 trials of racemic ketamine are needed. (Randomized Controlled Trial)
Randomized Controlled Trial
Efficacy and safety of a 4-week course of repeated subcutaneous ketamine injections for treatment-resistant depression (KADS study): randomised double-blind active-controlled trial.
BACKGROUND
Prior trials suggest that intravenous racemic ketamine is a highly effective for treatment-resistant depression (TRD), but phase 3 trials of racemic ketamine are needed.
AIMS
To assess the acute efficacy and safety of a 4-week course of subcutaneous racemic ketamine in participants with TRD. Trial registration: ACTRN12616001096448 at www.anzctr.org.au.
METHOD
This phase 3, double-blind, randomised, active-controlled multicentre trial was conducted at seven mood disorders centres in Australia and New Zealand. Participants received twice-weekly subcutaneous racemic ketamine or midazolam for 4 weeks. Initially, the trial tested fixed-dose ketamine 0.5 mg/kg versus midazolam 0.025 mg/kg (cohort 1). Dosing was revised, after a Data Safety Monitoring Board recommendation, to flexible-dose ketamine 0.5-0.9 mg/kg or midazolam 0.025-0.045 mg/kg, with response-guided dosing increments (cohort 2). The primary outcome was remission (Montgomery-Åsberg Rating Scale for Depression score ≤10) at the end of week 4.
RESULTS
The final analysis (those who received at least one treatment) comprised 68 in cohort 1 (fixed-dose), 106 in cohort 2 (flexible-dose). Ketamine was more efficacious than midazolam in cohort 2 (remission rate 19.6% . 2.0%; OR = 12.1, 95% CI 2.1-69.2, = 0.005), but not different in cohort 1 (remission rate 6.3% . 8.8%; OR = 1.3, 95% CI 0.2-8.2, = 0.76). Ketamine was well tolerated. Acute adverse effects (psychotomimetic, blood pressure increases) resolved within 2 h.
CONCLUSIONS
Adequately dosed subcutaneous racemic ketamine was efficacious and safe in treating TRD over a 4-week treatment period. The subcutaneous route is practical and feasible.
Topics: Humans; Ketamine; Depression; Midazolam; Australia; Depressive Disorder, Treatment-Resistant
PubMed: 38108319
DOI: 10.1192/bjp.2023.79 -
JAMA Surgery Feb 2024The effect of oral midazolam premedication on patient satisfaction in older patients undergoing surgery is unclear, despite its widespread use.
IMPORTANCE
The effect of oral midazolam premedication on patient satisfaction in older patients undergoing surgery is unclear, despite its widespread use.
OBJECTIVE
To determine the differences in global perioperative satisfaction in patients with preoperative administration of oral midazolam compared with placebo.
DESIGN, SETTING, AND PARTICIPANTS
This double-blind, parallel-group, placebo-controlled randomized clinical trial was conducted in 9 German hospitals between October 2017 and May 2019 (last follow-up, June 24, 2019). Eligible patients aged 65 to 80 years who were scheduled for elective inpatient surgery for at least 30 minutes under general anesthesia and with planned extubation were enrolled. Data were analyzed from November 2019 to December 2020.
INTERVENTIONS
Patients were randomized to receive oral midazolam, 3.75 mg (n = 309), or placebo (n = 307) 30 to 45 minutes prior to anesthesia induction.
MAIN OUTCOMES AND MEASURES
The primary outcome was global patient satisfaction evaluated using the self-reported Evaluation du Vécu de l'Anesthésie Generale (EVAN-G) questionnaire on the first postoperative day. Key secondary outcomes included sensitivity and subgroup analyses of the primary outcome, perioperative patient vital data, adverse events, serious complications, and cognitive and functional recovery up to 30 days postoperatively.
RESULTS
Among 616 randomized patients, 607 were included in the primary analysis. Of these, 377 (62.1%) were male, and the mean (SD) age was 71.9 (4.4) years. The mean (SD) global index of patient satisfaction did not differ between the midazolam and placebo groups (69.5 [10.7] vs 69.6 [10.8], respectively; mean difference, -0.2; 95% CI, -1.9 to 1.6; P = .85). Sensitivity (per-protocol population, multiple imputation) and subgroup analyses (anxiety, frailty, sex, and previous surgical experience) did not alter the primary results. Secondary outcomes did not differ, except for a higher proportion of patients with hypertension (systolic blood pressure ≥160 mm Hg) at anesthesia induction in the placebo group.
CONCLUSION AND RELEVANCE
A single low dose of oral midazolam premedication did not alter the global perioperative patient satisfaction of older patients undergoing surgery or that of patients with anxiety. These results may be affected by the low dose of oral midazolam. Further trials-including a wider population with commonplace low-dose intravenous midazolam and plasma level measurements-are needed.
TRIAL REGISTRATION
ClinicalTrials.gov Identifier: NCT03052660.
Topics: Aged; Humans; Male; Female; Midazolam; Double-Blind Method; Patient Satisfaction; Anesthesia, General; Personal Satisfaction; Patient-Centered Care
PubMed: 38117527
DOI: 10.1001/jamasurg.2023.6479 -
The Journal of Vascular Access Jul 2023Endovascular therapy, such as percutaneous transluminal angioplasty (PTA), stenting, or embolization, is a well-established form of treatment to prolong the lifespan of... (Review)
Review
BACKGROUND
Endovascular therapy, such as percutaneous transluminal angioplasty (PTA), stenting, or embolization, is a well-established form of treatment to prolong the lifespan of arteriovenous access. These procedures, especially PTA, can be accompanied with severe pain. We reviewed and analyzed the efficacy, safety, and outcome of sedoanalgesia using intravenous midazolam and fentanyl, for pain relief during these procedures.
METHODS
Two hundred and two consecutive patients with dysfunctional dialysis access that had undergone endovascular procedure in our institute between July and November 2017 were included in this study. The dialysis access profile, procedure complication, and 10-point Visual Analog Scale (VAS) were collected. One-year clinical follow-up record was also collected to evaluate arteriovenous access patency and long-term complications.
RESULTS
Among the 202 patients, the mean age was (mean ± SD) 67.0 ± 12.08 years. Dialysis access profile of these patients were 119 (58.9%) native arteriovenous fistula and 162 (74.2%) forearm access. The number of lesions treated were 1.63 ± 0.802.Immediate complications included 11 (5.44%) nausea/vomiting, 24 (11.88%) desaturation (SpO < 90%, resolved after pillow removal or jaw trust), 16 (7.9%) hypotension (SBP < 90 mmHg, resolved without inotropic agents). There was a low average pain score (1.16 ± 1.594) during the procedure with 136 (67.3%) no pain (VAS 0-1) and 56 (27.7%) mild pain (VAS 2-4). Higher VAS score correlated with overweight patients, longer PTA time and pain after procedure. Six-month primary patency rate was 49.17% and primary assisted patency rate was 93.04%.
CONCLUSIONS
Sedoanalgesia with intravenous midazolam and fentanyl is an easy, safe, and effective method for surgeons.
Topics: Humans; Middle Aged; Aged; Midazolam; Fentanyl; Vascular Patency; Retrospective Studies; Angioplasty; Renal Dialysis; Pain; Arteriovenous Shunt, Surgical; Angioplasty, Balloon; Treatment Outcome; Graft Occlusion, Vascular
PubMed: 34622684
DOI: 10.1177/11297298211050174 -
CNS Drugs Nov 2023Over the last decade, significant advancements have been made in status epilepticus (SE) management, influenced by landmark trials such as ESETT and RAMPART. The...
Trends and Differences in Status Epilepticus Treatment of Children and Adults Over 10 Years: A Comparative Study of Medical Records (2012-2021) from a University Hospital in Germany.
BACKGROUND AND OBJECTIVES
Over the last decade, significant advancements have been made in status epilepticus (SE) management, influenced by landmark trials such as ESETT and RAMPART. The objectives of this study were to explore the evolution of drug treatments for patients with SE, to investigate its association with outcomes and mortality, and to evaluate differences in treatment patterns between adults and children for a potential shift in medication trends due to the above mentioned trials.
METHODS
The medical records of patients with SE treated at University Hospital Frankfurt between 2012 and 2021 were evaluated for medication trends and outcomes. Children and adults were analyzed separately and jointly.
RESULTS
This study included 1151 SE episodes in 1021 patients (mean age = 53.3 ± 28.3 years; 52.5 % female [n = 533]). The overall percentage of patients with SE treated prehospital was stable over the last decade. More than half (53.6 %) of children were treated prehospital, compared with less than one-third (26.7 %) of adults. Prehospital midazolam use increased over time, while diazepam use decreased. Lorazepam was the most commonly used benzodiazepine in hospitals in 2012-2013, used in 40.8 % of all episodes. However, its use declined to 27.2 % in 2020-2021, while midazolam use increased to 44.0 %. While the use of older antiseizure medications (ASMs) such as phenobarbital (p = 0.02), phenytoin (p < 0.001), and valproate (p < 0.001) decreased, the use of newer ASMs such as levetiracetam and lacosamide significantly increased (p < 0.001). Propofol and continuous midazolam infusion remained the most used third-line therapy drugs. Overall mortality was 16.5 % at discharge and 18.9 % at 30 days. Mortality rates did not change between 2012 and 2021.
CONCLUSION
Midazolam has become the preferred benzodiazepine in pre- and in-hospital settings, both in children and adults. The same applies to the increased use of levetiracetam and lacosamide over time in children and adults, while phenobarbital, phenytoin, and valproate use decreased. Continuous midazolam infusion and propofol remain the most frequently used anesthetic drugs. Mortality and outcome remain stable despite changes in medication patterns.
Topics: Humans; Child; Adult; Female; Middle Aged; Aged; Aged, 80 and over; Male; Anticonvulsants; Phenytoin; Midazolam; Levetiracetam; Valproic Acid; Propofol; Lacosamide; Hospitals, University; Status Epilepticus; Phenobarbital; Benzodiazepines; Medical Records
PubMed: 37979095
DOI: 10.1007/s40263-023-01049-w -
Frontiers in Pharmacology 2023Colonoscopy plays an important role in the diagnosis, prognosis prediction, assessment of disease activity and severity, and treatment of inflammatory bowel disease...
Efficacy and safety analysis of midazolam combined with dezocine sedation and analgesia colonoscopy in patients with inflammatory bowel disease: a prospective single-center open study.
Colonoscopy plays an important role in the diagnosis, prognosis prediction, assessment of disease activity and severity, and treatment of inflammatory bowel disease (IBD)-related complications. However, some patients refuse to undergo colonoscopy due to perceived pain and other discomfort, their diagnosis and treatment are affected. Therefore, we conducted a prospective study to explore the efficacy and safety of midazolam combined with dezocine for sedation in IBD patients undergoing colonoscopy. 224 patients were divided into sedative-colonoscopy-group (SCG, n = 93), anesthesia-colonoscopy-group (ACG, n = 90) and ordinary-colonoscopy-group (OCG, n = 41). The vital signs (blood pressure, pulse, respiration and blood oxygen saturation), pain degree during colonoscopy, satisfaction and complication rates of the three groups were compared. Before colonoscopy, there was no significant difference among the vital signs of the three groups. The vital signs of the ACG were significantly lower than those of the SEG and the OCG ( < 0.05), and the difference was not significant between the SCG and OCG during colonoscopy. The colonoscopy pain score in the SCG was lower than that in the OCG (0.79 ± 1.09 vs. 2.98 ± 1.27, < 0.001). The satisfaction score of the SCG (9.26 ± 1.16) was not significantly different from that of the ACG (9.42 ± 1.41) but was higher than that of the OCG (6.63 ± 1.13) ( < 0.001). The total complication rate of the ACG was 45.56% (41/90), which was significantly higher than that of the SCG [20.43% (19/93)] and the OCG [19.51% (8/41)]. Colon perforation, abnormal blood pressure fluctuation and hypoxemia were significantly more common in the ACG than in the SCG and the OCG ( < 0.05). However, there was no significant difference in the incidence of complications between the SCG and OCG. Compared with ordinary-colonoscopy, colonoscopy performed under midazolam and dezocine sedation is more comfortable for patients, thereby increasing satisfaction and compliance. Colonoscopy that is performed under midazolam and dezocine is similar to colonoscopy that is anesthesia with propofol in terms of comfort, satisfaction and compliance and similar to ordinary-colonoscopy in terms of safety. Considering the shortage of anesthesiologists, the application of midazolam combined with dezocine for digestive endoscopy is worthy of clinical promotion.
PubMed: 37492093
DOI: 10.3389/fphar.2023.1150045 -
Clinical Pharmacokinetics Jul 2023Midazolam is the preferred clinical probe drug for assessing CYP3A activity. We have previously shown substantial intraindividual variability in midazolam absolute...
BACKGROUND AND OBJECTIVE
Midazolam is the preferred clinical probe drug for assessing CYP3A activity. We have previously shown substantial intraindividual variability in midazolam absolute bioavailability and clearance in patients with obesity before and after weight loss induced by gastric bypass or a strict diet. The objective was to describe intraindividual variability in absolute bioavailability and clearance of midazolam in healthy individuals without obesity.
METHODS
This study included 33 healthy volunteers [28 ± 8 years, 21% males, body mass index (BMI) 23 ± 2.5 kg/m] subjected to four pharmacokinetic investigations over a 2-month period (weeks 0, 2, 4, and 8). Semi-simultaneous oral (0 h) and intravenous (2 h later) midazolam dosing was used to assess absolute bioavailability and clearance of midazolam.
RESULTS
At baseline, mean absolute bioavailability and clearance were 46 ± 18% and 31 ± 10 L/h, respectively. The mean coefficient of variation (CV, %) for absolute bioavailability and clearance of midazolam was 26 ± 15% and 20 ± 10%, respectively. Approximately one-third had a CV > 30% for absolute bioavailability, while 13% had a CV > 30% for clearance.
CONCLUSIONS
On average, intraindividual variability in absolute bioavailability and clearance of midazolam was low to moderate; however, especially absolute bioavailability showed considerable variability in a relatively large proportion of the individuals.
Topics: Male; Humans; Female; Midazolam; Biological Availability; Cytochrome P-450 CYP3A; Administration, Intravenous; Obesity; Administration, Oral
PubMed: 37162619
DOI: 10.1007/s40262-023-01257-z -
Brazilian Journal of Anesthesiology... 2023Up to 60% of pediatric surgical patients develop high levels of preoperative anxiety. This study compared the effects of oral combinations of midazolam and ketamine with... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Up to 60% of pediatric surgical patients develop high levels of preoperative anxiety. This study compared the effects of oral combinations of midazolam and ketamine with oral midazolam alone for pediatric preanesthetic medication.
METHODS
The study protocol was registered in PROSPERO as CRD42020172920. A systematic literature search was conducted using Medline, Cochrane, EMBASE, CENTRAL, and Web of Science for randomized controlled trials comparing oral combinations of midazolam and ketamine with midazolam alone as preanesthetic medication in elective surgical pediatric patients. Meta-analyses included the following outcomes: anxiety and sedation levels, child...s behavior during separation from parents, face mask acceptance, and venipuncture. The quality of evidence was assessed using GRADE criteria.
RESULTS
Twenty studies were included. The following effects (RR (95% CI)) were observed for combinations of ketamine and midazolam relative midazolam alone: anxiolysis (1.2 (0.94...1.52); p.ß=.ß0.15; I2.ß=.ß80%; GRADE.ß=.ßvery low); satisfactory sedation (1.2 ( 1.10...1.31); p.ß<.ß0.001; I2.ß=.ß71%; GRADE.ß=.ßvery low); behavior during parental separation (1.2 (1.06...1.36); p.ß=.ß0.003; I2.ß=.ß88%; GRADE.ß=.ßvery low); facial mask acceptance (1.13 (1.04...1.24); p.ß=.ß0.007; I2.ß=.ß49%; GRADE.ß=.ßvery low); behavior during venipuncture (1.32 (1.11...1.57); p.ß=.ß0.002; I2.ß=.ß66%; GRADE.ß=.ßvery low).
CONCLUSIONS
While similar probabilities of obtaining anxiolysis were found, adequate sedation, calm behavior during child...s separation from parents, low levels of fear during face mask adaptation, and cooperative behavior during peripheral venous cannulation were more likely with midazolam-ketamine combinations.
Topics: Child; Humans; Midazolam; Ketamine; Preanesthetic Medication; Anxiety; Anesthesia; Hypnotics and Sedatives
PubMed: 34411631
DOI: 10.1016/j.bjane.2021.07.026 -
Alternative Therapies in Health and... Jun 2024This study aimed to compare the direct medication costs and clinical effectiveness of using remimazolam versus midazolam for goal-guided sedation therapy in the ICU...
OBJECTIVE
This study aimed to compare the direct medication costs and clinical effectiveness of using remimazolam versus midazolam for goal-guided sedation therapy in the ICU patients.
METHODS
This randomized controlled study was conducted in the ICU of People's Hospital Affiliated to Shandong First Medical University. Eighty adult patients admitted to the ICU and requiring sedation were enrolled and randomly assigned in a 1:1 ratio to receive either remimazolam-based sedation (study group, n=40) or midazolam-based sedation (control group, n=40). The inclusion criteria for patient selection were age 18-80 years, requirement for mechanical ventilation, and an expected ICU stay of at least 24 hours. Patients with significant liver or kidney dysfunction, neurological disorders, or contraindications to the study drugs were excluded. The target sedation depth for both groups was a Ramsay Sedation Scale score of 3-4, which was maintained by titrating the infusion rates of remimazolam or midazolam as needed. Vital signs, sedation scores, and respiratory parameters were closely monitored throughout the sedation period.
RESULTS
The time to onset of sedation, time to reach the target sedation depth, time to awakening, and length of ICU stay were all significantly shorter in the remimazolam group compared to the midazolam group (P < .05 for all). The remimazolam group had a mean time to onset of 5.2 ± 1.8 minutes versus 8.9 ± 2.4 minutes in the midazolam group. The mean time to reach the target Ramsay Sedation Scale score of 3-4 was 12.6 ± 3.1 minutes in the remimazolam group compared to 18.4 ± 4.2 minutes in the midazolam group. The mean time to awakening was 10.2 ± 2.7 minutes in the remimazolam group versus 16.5 ± 3.9 minutes in the midazolam group. The remimazolam group also had a significantly shorter mean ICU length of stay of 5.1 ± 1.3 days compared to 7.8 ± 2.1 days in the midazolam group (P < .01). The remimazolam group had a significantly higher metabolic clearance rate compared to the midazolam group (P < .001). The Ramsay sedation scores and Wong-Baker FACES pain scores were also significantly lower in the remimazolam group throughout the sedation period (P < .01). There were no significant differences in heart rate between the two groups at any timepoint. However, the overall incidence of adverse events was significantly lower in the remimazolam group compared to the midazolam group (P < .05).
CONCLUSION
This study demonstrated that the use of remimazolam-based goal-directed sedation in the ICU setting resulted in significantly faster onset of action, quicker achievement of the target sedation depth, shorter time to awakening, and shorter ICU length of stay compared to midazolam-based sedation. The remimazolam group also had a higher metabolic clearance rate, lower sedation and pain scores, and a lower incidence of adverse events.These findings suggest that remimazolam may provide advantages over midazolam for ICU sedation, potentially leading to improved patient comfort, more efficient utilization of ICU resources, and potentially better clinical outcomes. The rapid onset, titratability, and favorable safety profile of remimazolam make it a promising sedative agent that could help optimize sedation practices in the critical care setting. Further research is warranted to fully evaluate the impact of remimazolam on long-term patient-centered outcomes and overall healthcare costs in the ICU.
PubMed: 38843423
DOI: No ID Found