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Anesthesia and Analgesia Mar 2016Research has shown that high-risk surgical patients benefit from a multimodal therapeutic approach to prevent postoperative nausea and vomiting (PONV). Our group sought... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Research has shown that high-risk surgical patients benefit from a multimodal therapeutic approach to prevent postoperative nausea and vomiting (PONV). Our group sought to investigate the effect of administering IV midazolam on PONV.
METHODS
This meta-analysis included 12 randomized controlled trials (n = 841) of adults undergoing a variety of surgical procedures that investigated the effect of both preoperative and intraoperative IV midazolam on PONV in patients undergoing general anesthesia.
RESULTS
Administration of IV midazolam was associated with significantly reduced PONV (risk ratio [RR] = 0.55; 95% confidence interval [CI], 0.43-0.70), nausea (RR = 0.62; 95% CI, 0.40-0.94), vomiting (RR = 0.61; 95% CI, 0.45-0.82), and rescue antiemetic administration (RR = 0.49; 95% CI, 0.37-0.65) within 24 hours. Individual subgroup analyses of trials excluding the use of thiopental for induction, trials of either female sex or high-risk surgery, trials involving nitrous oxide maintenance, and trials using midazolam in combination with known antiemetics all yielded similar reductions in PONV end points within 24 hours of surgery.
CONCLUSIONS
Administration of preoperative or intraoperative IV midazolam is associated with a significant decrease in overall PONV, nausea, vomiting, and rescue antiemetic use. Providers may consider the administration of IV midazolam as part of a multimodal approach in preventing PONV.
Topics: Antiemetics; Humans; Injections, Intravenous; Midazolam; Postoperative Nausea and Vomiting; Randomized Controlled Trials as Topic
PubMed: 26332858
DOI: 10.1213/ANE.0000000000000941 -
American Journal of Veterinary Research May 2017OBJECTIVE To determine the pharmacokinetic and pharmacodynamic effects of midazolam following IV and IM administration in sheep. ANIMALS 8 healthy adult rams. PROCEDURES... (Clinical Trial)
Clinical Trial
OBJECTIVE To determine the pharmacokinetic and pharmacodynamic effects of midazolam following IV and IM administration in sheep. ANIMALS 8 healthy adult rams. PROCEDURES Sheep were administered midazolam (0.5 mg/kg) by the IV route and then by the IM route 7 days later in a crossover study. Physiologic and behavioral variables were assessed and blood samples collected for determination of plasma midazolam and 1-hydroxymidazolam (primary midazolam metabolite) concentrations immediately before (baseline) and at predetermined times for 1,440 minutes after midazolam administration. Pharmacokinetic parameters were calculated by compartmental and noncompartmental methods. RESULTS Following IV administration, midazolam was rapidly and extensively distributed and rapidly eliminated; mean ± SD apparent volume of distribution, elimination half-life, clearance, and area under the concentration-time curve were 838 ± 330 mL/kg, 0.79 ± 0.44 hours, 1,272 ± 310 mL/h/kg, and 423 ± 143 h·ng/mL, respectively. Following IM administration, midazolam was rapidly absorbed and bioavailability was high; mean ± SD maximum plasma concentration, time to maximum plasma concentration, area under the concentration-time curve, and bioavailability were 820 ± 268 ng/mL, 0.46 ± 0.26 hours, 1,396 ± 463 h·ng/mL, and 352 ± 148%, respectively. Respiratory rate was transiently decreased from baseline for 15 minutes after IV administration. Times to peak sedation and ataxia after IV administration were less than those after IM administration. CONCLUSIONS AND CLINICAL RELEVANCE Results indicated midazolam was a suitable short-duration sedative for sheep, and IM administration may be a viable alternative when IV administration is not possible.
Topics: Administration, Intravenous; Animals; Biological Availability; Cross-Over Studies; Half-Life; Hypnotics and Sedatives; Injections, Intramuscular; Male; Midazolam; Respiratory Rate; Sheep
PubMed: 28441044
DOI: 10.2460/ajvr.78.5.539 -
Anesthesia and Analgesia Mar 2016
Topics: Antiemetics; Humans; Midazolam; Postoperative Nausea and Vomiting
PubMed: 26891384
DOI: 10.1213/ANE.0000000000001128 -
The Journal of Emergency Medicine Dec 2021Although the efficacy and safety profiles of both intranasal fentanyl and midazolam are well studied in pediatric patients, few studies examine their use in younger...
BACKGROUND
Although the efficacy and safety profiles of both intranasal fentanyl and midazolam are well studied in pediatric patients, few studies examine their use in younger children.
OBJECTIVES
To examine and report our experiences in a pediatric emergency department (ED) with intranasal fentanyl and midazolam in children aged 3 years and younger.
METHODS
This retrospective study investigated intranasal fentanyl and midazolam administration, alone and in combination, in children 3 years and younger treated in a pediatric ED.
RESULTS
Of 6198 patients included, 1762 received intranasal fentanyl alone, 1115 received intranasal midazolam alone, and 3321 received combination therapy. The median (interquartile range [IQR]) patient age was 2.2 (1.5-3) years. Initial median (IQR) fentanyl dose was 2.7 (2-3) µg/kg, with 13.3% receiving a repeat dose. Initial median (IQR) midazolam dose was 0.3 (0.2-0.3) mg/kg, with 3.3% receiving a second dose. Children receiving both fentanyl and midazolam had median (IQR) initial doses of 2.8 (2.1-3) µg/kg and 0.3 (0.2-0.3) mg/kg, respectively. Of these, 3.2% received repeat doses of both medications. Laceration repairs (33.8%) and incision and drainage (22.2%) accounted for the majority of indications. Only 2.9% (n = 178) received additional opioids. No serious adverse events requiring a reversal agent or respiratory support were reported.
CONCLUSIONS
Intranasal fentanyl and midazolam, alone and in combination, can provide analgesia and anxiolysis to children aged 3 years and younger in the ED setting. Further prospective studies are needed to better evaluate their safety and efficacy in this younger population.
Topics: Administration, Intranasal; Child; Child, Preschool; Emergency Service, Hospital; Fentanyl; Humans; Midazolam; Retrospective Studies
PubMed: 34920841
DOI: 10.1016/j.jemermed.2021.09.006 -
Journal of Stroke and Cerebrovascular... Dec 2021The ideal anesthetic for mechanical thrombectomy (MT) is a subject of debate. Recent studies have supported the use of monitored anesthesia care (MAC), but few have... (Comparative Study)
Comparative Study
OBJECTIVES
The ideal anesthetic for mechanical thrombectomy (MT) is a subject of debate. Recent studies have supported the use of monitored anesthesia care (MAC), but few have attempted to compare MAC neuroanesthetics. Our study directly compares midazolam and dexmedetomidine (DEX) on blood pressure control during thrombectomy and functional outcomes at discharge.
MATERIALS AND METHODS
We performed a retrospective review of an MT database, which consisted of 612 patients admitted between 2010-2019 to our tertiary stroke center. 193 patients who received either midazolam or DEX for MAC induction were identified. Primary and secondary outcomes were >20% maximum decrease in mean arterial pressure during MT and functional independence respectively.
RESULTS
146 patients were administered midazolam, while 47 were administered DEX. Decrease in blood pressure (BP) during MT was associated with lower rates of functional independence at last follow-up (p=0.034). When compared to midazolam, DEX had significantly higher rates of intraprocedural decrease in MAP at the following cut-offs: >20% (p<0.001), >30% (p=0.001), and >40% (p=0.006). On multivariate analysis, DEX was an independent predictor of >20% MAP decrease (OR 7.042, p<0.001). At time of discharge, NIHSS scores and functional independence (mRS 0-2) were statistically similar between DEX and midazolam. Functional independence at last known follow-up was statistically similar between DEX and midazolam (p = 0.643).
CONCLUSIONS
Use of DEX during MT appears to be associated with increased blood pressure volatility when compared to midazolam. Further investigation is needed to determine the impact of MAC agents on functional independence.
Topics: Anesthetics; Blood Pressure; Dexmedetomidine; Humans; Midazolam; Retrospective Studies; Thrombectomy; Treatment Outcome
PubMed: 34656971
DOI: 10.1016/j.jstrokecerebrovasdis.2021.106117 -
Journal of Avian Medicine and Surgery Nov 2022Chickens () often undergo veterinary procedures requiring sedation; however, there is little published research evaluating the efficacy of sedation protocols in this...
Chickens () often undergo veterinary procedures requiring sedation; however, there is little published research evaluating the efficacy of sedation protocols in this species. The objective of this study was to assess the effects of intramuscular alfaxalone and midazolam compared with intramuscular butorphanol and midazolam in chickens. In a complete crossover study, 11 healthy adult hens were randomly administered midazolam 2.5 mg/kg IM combined with either alfaxalone 15 mg/kg IM (AM, n = 11) or butorphanol 3 mg/kg IM (BM, n = 11), with a 35-day washout period between groups. Time to first effects, recumbency, standing, and recovery were recorded. Physiologic parameters and sedation scores were recorded every 5 minutes by 2 blinded investigators. Fifteen minutes after injection, positioning for sham whole body radiographs was attempted. At 30 minutes, flumazenil 0.05 mg/kg IM was administered to all hens. Peak total sedation score was significantly higher for AM compared with BM ( < 0.001). Mean ± SD or median (range) time to initial effects, recumbency, standing, and recovery in AM and BM were 1.9 ± 0.6 and 2.6 ± 0.9 ( = 0.02), 3.5 (1.6-7.6) and 4.8 (2.2-13.0) ( = 0.10), 40.3 (28.0-77.8) and 33.2 (5.2-41.3) ( = 0.15), and 71.2 (45.7-202.3) and 39.9 (35.9-45.9) minutes ( = 0.05), respectively. Radiographic positioning was successful in 6 of 11 (54.5%) and 0 of 11 (0%) birds in the AM and BM groups at 15 minutes, respectively. Heart and respiratory rates remained within acceptable clinical limits for all birds. Intramuscular AM resulted in significantly faster onset of sedative effects, significantly longer duration of recumbency, significantly higher peak sedation, and improved success of radiographic positioning compared with intramuscular BM. Intramuscular AM produces clinically effective sedation in chickens without clinically significant cardiorespiratory effects.
Topics: Animals; Female; Butorphanol; Midazolam; Chickens; Cross-Over Studies; Rhode Island
PubMed: 36468806
DOI: 10.1647/20-00087 -
Respiratory Investigation May 2022Disinhibition is sometimes experienced during bronchoscopy with sedation. However, data on disinhibition during bronchoscopy are scarce. We examined the prevalence and...
BACKGROUND
Disinhibition is sometimes experienced during bronchoscopy with sedation. However, data on disinhibition during bronchoscopy are scarce. We examined the prevalence and characteristics of disinhibition during bronchoscopy with midazolam.
METHODS
This retrospective study analyzed consecutive patients who underwent bronchoscopy between November 2019 and December 2020. The severity of disinhibition was defined as follows: mild, disinhibition sometimes requiring restraints by assistants; moderate, disinhibition always requiring restraints by assistants; and severe, disinhibition requiring antagonization of sedation by flumazenil to continue bronchoscopy.
RESULTS
Among 251 eligible patients who were sedated using midazolam, 36 (14.3%; 95% confidence interval [CI], 10.5%-19.2%), 42 (16.7%; 95% CI, 12.6%-21.8%), and 7 (2.8%; 95% CI, 1.4%-5.6%) experienced mild, moderate, and severe disinhibition, respectively. Depression (odds ratio [OR] 2.77; 95% CI, 1.20-6.41), endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) (OR 10.23; 95% CI, 1.02-103.01, referred to brushing/bronchial washing/observation), and increased administration of midazolam (OR 1.20; 95% CI, 1.02-1.42, per 1-mg increase) were independently associated with moderate-to-severe disinhibition. Patients experiencing moderate disinhibition reported significantly better scores for discomfort during bronchoscopy. Besides the maximum systolic and diastolic blood pressures during bronchoscopy, the changes in hemodynamic and respiratory statuses during bronchoscopy or complications did not significantly differ between patients experiencing moderate-to-severe disinhibition and those experiencing none-to-mild disinhibition.
CONCLUSIONS
Moderate-to-severe disinhibition occurred in 19.5% of patients during bronchoscopy with midazolam. We should focus on disinhibition when patients have depression or are planning to undergo EBUS-TBNA, and sparing the administration of midazolam might reduce the occurrence of disinhibition.
CLINICAL TRIAL REGISTRATION
UMIN000038571.
Topics: Bronchoscopy; Endoscopic Ultrasound-Guided Fine Needle Aspiration; Humans; Midazolam; Prevalence; Retrospective Studies
PubMed: 34969650
DOI: 10.1016/j.resinv.2021.11.010 -
Physiology & Behavior May 2023Phenotypes of inbred mice are strain-dependent, indicating the important influence of genetic background in biomedical research. C57BL/6 is one of the most commonly used...
Phenotypes of inbred mice are strain-dependent, indicating the important influence of genetic background in biomedical research. C57BL/6 is one of the most commonly used inbred mouse strains, and its two closely related substrains, C57BL/6J and C57BL/6N, have been separated for only about 70 years. These two substrains have accumulated genetic variations and exhibit different phenotypes, but it remains unclear whether they respond to anesthetics differently. In this study, commercially acquired wildtype C57BL/6J or C57BL/6N mice from two different sources were analyzed and compared for their response to a spectrum of anesthetics (midazolam, propofol, esketamine or isoflurane anesthesia) and their performance in a series of behavioral tests associated with neurological functions including open field test (OFT), elevated plus maze (EPM), Y maze, prepulse inhibition (PPI), tail strain test (TST) and forced swimming test (FST). Loss of the righting reflex (LORR) is used to measure the anesthetic effects. Our results suggested that the anesthesia induction time induced by either of the four anesthetics were comparable for the C57BL/6J and C57BL/6N mice. However, C57BL/6J or C57BL/6N mice do exhibit different sensitivity to midazolam and propofol. The anesthesia duration of midazolam of C57BL/6J mice was about 60% shorter than that of the C57BL/6N mice, while the LORR duration induced by propofol in C57BL/6J mice was 51% longer than that of the C57BL/6N. In comparison, the two substrains were anesthetized by esketamine or isoflurane similarly. In the behavioral analysis, the C57BL/6J mice exhibited a lower level of anxiety- and depression-like behaviors in OFT, EPM, FST and TST than the C57BL/6N mice. Locomotor activity and sensorimotor gating of these two substrains remained comparable. Our results stress the point that when selecting inbred mice for allele mutation or behavioral testing, the influence of even subtle differences in genetic background should be fully considered.
Topics: Mice; Animals; Propofol; Midazolam; Mice, Inbred C57BL; Isoflurane; Mice, Inbred Strains; Anesthetics; Anesthesia
PubMed: 36889487
DOI: 10.1016/j.physbeh.2023.114146 -
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 -
British Journal of Clinical Pharmacology Nov 2015In view of the increasing prevalence of obesity in adolescents, the aim of this study was to determine the pharmacokinetics of the CYP3A substrate midazolam and its... (Observational Study)
Observational Study
AIM
In view of the increasing prevalence of obesity in adolescents, the aim of this study was to determine the pharmacokinetics of the CYP3A substrate midazolam and its metabolites in overweight and obese adolescents.
METHODS
Overweight (BMI for age ≥ 85(th) percentile) and obese (BMI for age ≥ 95(th) percentile) adolescents undergoing surgery received 2 or 3 mg intravenous midazolam as a sedative drug pre-operatively. Blood samples were collected until 6 or 8 h post-dose. Population pharmacokinetic modelling and systematic covariate analysis were performed using nonmem 7.2.
RESULTS
Nineteen overweight and obese patients with a mean body weight of 102.7 kg (62-149.8 kg), a mean BMI of 36.1 kg m(-2) (24.8-55 kg m(-2)), and a mean age of 15.9 years (range 12.5-18.9 years) were included. In the model for midazolam and metabolites, total body weight was not of influence on clearance (0.66 l min(-1) (RSE 8.3%)), while peripheral volume of distribution of midazolam (154 l (11.2%)), increased substantially with total body weight (P < 0.001). The increase in peripheral volume could be explained by excess body weight (WTexcess ) instead of body weight related to growth (WTfor age and length ).
CONCLUSIONS
The pharmacokinetics of midazolam and its metabolites in overweight and obese adolescents show a marked increase in peripheral volume of distribution and a lack of influence on clearance. The findings may imply a need for a higher initial infusion rate upon initiation of a continuous infusion in obese adolescents.
Topics: Adolescent; Body Weight; Child; Female; Humans; Hypnotics and Sedatives; Male; Midazolam; Models, Biological; Obesity; Overweight; Prospective Studies
PubMed: 26044579
DOI: 10.1111/bcp.12693