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Veterinary Anaesthesia and Analgesia Nov 2019To evaluate drug interactions between fluconazole and the intravenous (IV) anesthetic induction agents, ketamine and midazolam.
OBJECTIVE
To evaluate drug interactions between fluconazole and the intravenous (IV) anesthetic induction agents, ketamine and midazolam.
STUDY DESIGN
Randomized parallel study.
ANIMALS
A group of 12 adult healthy Beagle dogs.
METHODS
Dogs were randomly allocated to two groups of six dogs. Dogs in group KM were administered IV ketamine (7 mg kg) and IV midazolam (0.25 mg kg), and dogs in group KMF were administered fluconazole (5 mg kg) orally 12 and 24 hours prior to ketamine-midazolam using the same doses as KM. Sedation scores (0-4) were assigned by investigators unaware of group assignment. Heart rate (HR) and times to sternal and standing were obtained and compared between groups for differences with p < 0.05 considered statistically significant. Blood was obtained and plasma drug concentrations were measured using liquid chromatography-mass spectrometry.
RESULTS
The times to sternal, mean 32.3 and 24.6 minutes, for groups KMF and KM, respectively, were not different between the groups. The time to standing, 73 and 36 minutes in groups KMF and KM, respectively, was significantly different (p = 0.002). The duration of elevated HR compared with baseline was longer in KMF (110 minutes) than in KM (25 minutes) (p < 0.05). In group KMF, one dog developed hyperthermia (40.6 °C), which resolved spontaneously. The clearance of ketamine and midazolam was significantly slower (approximately 50%) and the area under the curves were significantly higher (two-fold) in group KMF (p = 0.02).
CONCLUSIONS AND CLINICAL RELEVANCE
A significant interaction between oral fluconazole and IV ketamine-midazolam occurred, but the effects appear minor in healthy dogs. Based on these data, a single dose of ketamine-midazolam is not contraindicated in dogs treated with fluconazole, but the duration of effects and pharmacokinetics are altered.
Topics: Administration, Intravenous; Administration, Oral; Animals; Area Under Curve; Dogs; Drug Interactions; Female; Fluconazole; Half-Life; Ketamine; Male; Midazolam
PubMed: 31401049
DOI: 10.1016/j.vaa.2019.06.007 -
CJEM Mar 2022
Topics: Anesthetics, Dissociative; Haloperidol; Humans; Hypnotics and Sedatives; Ketamine; Midazolam
PubMed: 34971446
DOI: 10.1007/s43678-021-00249-x -
Veterinary Anaesthesia and Analgesia Jan 2022To compare the sedative and cardiopulmonary effects of intranasal (IN) and intramuscular (IM) administration of dexmedetomidine and midazolam combination in New Zealand...
OBJECTIVE
To compare the sedative and cardiopulmonary effects of intranasal (IN) and intramuscular (IM) administration of dexmedetomidine and midazolam combination in New Zealand White rabbits.
STUDY DESIGN
A randomized, crossover experimental study.
ANIMALS
A total of eight healthy New Zealand White rabbits, aged 6-12 months, weighing 3.1 ± 0.3 kg (mean ± standard deviation).
METHODS
The animals were randomly assigned to administration of dexmedetomidine (0.1 mg kg) with midazolam (2 mg kg) by either IN or IM route separated by 2 weeks. The electrocardiogram, pulse rate (PR), peripheral haemoglobin oxygen saturation (SpO), mean noninvasive arterial pressure (MAP), respiratory frequency (f) and rectal temperature were measured before drug administration (baseline), T (onset of sedation) and at 5 minute intervals until recovery. The onset of sedation, duration of sedation and sedation score (SS) were also recorded.
RESULTS
The PR was significantly lower in treatment IM than in treatment IN over time (p = 0.027). MAP < 60 mmHg developed in two and four rabbits in treatments IN and IM, respectively. SpO progressively decreased over time in both treatments. f was lower than baseline at several time points in both treatments. Onset of sedation was shorter in treatment IN (90 ± 21 seconds) than in treatment IM (300 ± 68 seconds) (p = 0.036). Duration of sedation was longer in treatment IM (55.2 ± 8.7 minutes) than in treatment IN (39.6 ± 2.1 minutes) (p = 0.047). No significant difference in SS was observed between treatments (p > 0.05).
CONCLUSIONS AND CLINICAL RELEVANCE
Combination of dexmedetomidine (0.1 mg kg) and midazolam (2 mg kg) decreased f, PR and SpO regardless of the administration route in New Zealand White rabbits. A more rapid action and shorter duration of sedation were observed after treatment IN than after treatment IM administration.
Topics: Administration, Intranasal; Animals; Dexmedetomidine; Heart Rate; Hypnotics and Sedatives; Injections, Intramuscular; Midazolam; Oxygen Saturation; Rabbits
PubMed: 34802925
DOI: 10.1016/j.vaa.2021.10.003 -
British Journal of Anaesthesia Apr 2022Anaesthesia and perioperative management contribute to long-term outcomes of patients with cancer, including pancreatic ductal adenocarcinoma. We assessed the...
BACKGROUND
Anaesthesia and perioperative management contribute to long-term outcomes of patients with cancer, including pancreatic ductal adenocarcinoma. We assessed the antitumour, anti-inflammatory, and analgesic effects of midazolam on LSL-Kras;Trp53;Pdx-1 transgenic mice with pancreatic ductal adenocarcinoma.
METHODS
Six-week-old transgenic mice were administered midazolam 30 mg kg day p.o. (n=13); midazolam 30 mg kg day with 1-(2-chlorophenyl)-N-methyl-N(1-methylpropyl)-3-isoquinoline carboxamide (PK11195) 3 mg kg day i.p., a peripheral benzodiazepine receptor antagonist (n=10); or vehicle (water; n=14) until the humane endpoint. Cancer-associated pain was evaluated using hunching score and mouse grimace scale. Tumour stage and immuno-inflammatory status were determined histopathologically. Anti-proliferative and apoptotic potentials of midazolam were investigated using mouse pancreatic ductal adenocarcinoma cell lines.
RESULTS
Midazolam significantly inhibited tumour size and proliferative index of Ki-67 and cyclins in pancreatic ductal adenocarcinoma, which was blocked by administration of PK11195. Local myeloperoxidase tumour-associated neutrophils, arginase-1 M2-like tumour-associated macrophages, and CD11bLy-6G polymorphonuclear myeloid-derived suppressor cells were reduced by midazolam, which was antagonised by administration of PK11195. Hunching and mouse grimace scale were improved by midazolam, whereas the scores increased with midazolam+PK11195 treatment. Plasma pro-inflammatory cytokines, such as interleukin-6 and CC chemokine ligand (CCL)2, CCL3, and CCL5, were reduced by midazolam, whereas these cytokines increased with PK11195. Midazolam inhibited pancreatic ductal adenocarcinoma proliferation through downregulation of cyclins and cyclin-dependent kinases and induced apoptosis in vitro.
CONCLUSIONS
These results suggest that midazolam inhibits pancreatic ductal adenocarcinoma proliferation and local infiltration of tumour-associated neutrophils, tumour-associated macrophages, and polymorphonuclear myeloid-derived suppressor cells, thereby inhibiting pancreatic ductal adenocarcinoma progression.
Topics: Animals; Carcinoma, Pancreatic Ductal; Disease Models, Animal; Humans; Mice; Mice, Transgenic; Midazolam; Pancreatic Neoplasms
PubMed: 35120712
DOI: 10.1016/j.bja.2021.12.042 -
PloS One 2015To assess the efficacy of midazolam for anxiety control in third molar extraction surgery. (Review)
Review
PURPOSE
To assess the efficacy of midazolam for anxiety control in third molar extraction surgery.
METHODS
Electronic retrievals were conducted in Medline (via PubMed, 1950-2013.12), the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2013, Issue 3), Embase (via OVID 1974-2013.12), and the System for Information on Grey Literature in Europe (SIGLE). The bibliographies of relevant clinical trials were also checked. Randomized controlled trials satisfying the inclusion criteria were evaluated, with data extraction done independently by two well-trained investigators. Disagreements were resolved by discussion or by consultation with a third member of the review team.
RESULTS
Ten studies were included, but meta-analysis could not be conducted because of the significant differences among articles. All but one article demonstrated that midazolam could relieve anxiety. One article demonstrated that propofol offered superior anxiolysis, with more rapid recovery than with midazolam. Compared with lorazepam and diazepam, midazolam did not distinctly dominate in its sedative effect, but was safer. Two articles used midazolam in multidrug intravenous sedation and proved it to be more effective than midazolam alone.
CONCLUSION
It was found, by comparison and analysis, that midazolam might be effective for use for anxiety control during third molar extraction and can be safely administered by a dedicated staff member. It can also be used with other drugs to obtain better sedative effects, but the patient's respiratory function must be monitored closely, because multidrug sedation is also more risky.
Topics: Anti-Anxiety Agents; Anxiety; Clinical Trials as Topic; Female; Humans; MEDLINE; Male; Midazolam; Molar; Tooth Extraction
PubMed: 25849859
DOI: 10.1371/journal.pone.0121410 -
Current Medical Research and Opinion May 2023Sedation is common practice in endoscopic procedures to suppress a patient's level of consciousness while maintaining the cardio-respiratory function. Midazolam and...
BACKGROUND
Sedation is common practice in endoscopic procedures to suppress a patient's level of consciousness while maintaining the cardio-respiratory function. Midazolam and propofol are the sedatives most frequently used for procedural sedation at hospitals in Scandinavia. Remimazolam is a new ultra-short-acting benzodiazepine sedative and the present analysis aimed at estimating the economic benefits of introducing remimazolam for procedural sedation in colonoscopies and bronchoscopies in hospitals in Scandinavia.
METHOD
We developed a cost model applying a micro-costing approach that comprised the cost components that are affected by differences in the efficacy of remimazolam, midazolam, and propofol, and the model estimated the cost per successful colonoscopy and bronchoscopy when using remimazolam, midazolam or propofol as sedation. A micro-costing approach was applied, and the model consisted of six stages representing the journey for patients undergoing endoscopies and was informed primarily by data from clinical studies on remimazolam.
RESULTS
We found a total cost of DKK 1200 per successful colonoscopy procedure when using remimazolam, a total cost of DKK 1320 when using midazolam, and a total cost of DKK 1255 when using propofol. Hence, the incremental saving per successful colonoscopy procedure of using remimazolam was estimated to be DKK 120 compared to midazolam and DKK 55 compared to propofol. The total cost per successful bronchoscopy procedure when using remimazolam was DKK 1353 and DKK 1724 for midazolam, resulting in an incremental saving per bronchoscopy of DKK 372 when using remimazolam. Performed sensitivity analyses identified the time in recovery as the largest contributor to uncertainty in the analyses of remimazolam compared to midazolam in colonoscopies and bronchoscopies. In the comparison of remimazolam and propofol in colonoscopies, procedure time was the largest contributor to uncertainty.
CONCLUSION
We found that procedural sedation with remimazolam was associated with economically meaningful savings compared to procedural sedation with midazolam and propofol in colonoscopies and to midazolam in bronchoscopies.
Topics: Humans; Midazolam; Propofol; Bronchoscopy; Conscious Sedation; Benzodiazepines; Hypnotics and Sedatives; Colonoscopy
PubMed: 36999319
DOI: 10.1080/03007995.2023.2196198 -
Epilepsia Open Dec 2021Cholinergic-induced status epilepticus (SE) is associated with a loss of synaptic gamma-aminobutyric acid A receptors (GABA R) and an increase in N-methyl-D-aspartate...
OBJECTIVE
Cholinergic-induced status epilepticus (SE) is associated with a loss of synaptic gamma-aminobutyric acid A receptors (GABA R) and an increase in N-methyl-D-aspartate receptors (NMDAR) and amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPAR) that may contribute to pharmacoresistance when treatment with benzodiazepine antiseizure medication is delayed. The barbiturate phenobarbital enhances inhibitory neurotransmission by binding to a specific site in the GABA R to increase the open state of the channel, decrease neuronal excitability, and reduce glutamate-induced currents through AMPA/kainate receptors. We hypothesized that phenobarbital as an adjunct to midazolam would augment the amelioration of soman-induced SE and associated neuropathological changes and that further protection would be provided by the addition of an NMDAR antagonist.
METHODS
We investigated the efficacy of combining antiseizure medications to include a benzodiazepine and a barbiturate allosteric GABA R modulator (midazolam and phenobarbital, respectively) to correct loss of inhibition, and ketamine to reduce excitation caused by increased synaptic localization of NMDAR and AMPAR, which are NMDA-dependent. Rats implanted with transmitters to record electroencephalographic (EEG) activity were exposed to soman and treated with atropine sulfate and HI-6 one min after exposure and with antiseizure medication(s) 40 minutes after seizure onset.
RESULTS
The triple therapy combination of phenobarbital, midazolam, and ketamine administered at 40 minutes after seizure onset effectively prevented soman-induced epileptogenesis and reduced neurodegeneration. In addition, dual therapy with phenobarbital and midazolam or ketamine was more effective than monotherapy (midazolam or phenobarbital) in reducing cholinergic-induced toxicity.
SIGNIFICANCE
Benzodiazepine efficacy is drastically reduced with time after seizure onset and inversely related to seizure duration. To overcome pharmacoresistance in severe benzodiazepine-refractory cholinergic-induced SE, simultaneous drug combination to include drugs that target both the loss of inhibition (eg, midazolam, phenobarbital) and the increased excitatory response (eg, ketamine) is more effective than benzodiazepine or barbiturate monotherapy.
Topics: Animals; Anticonvulsants; Brain; Drug Therapy, Combination; Ketamine; Midazolam; Phenobarbital; Rats; Soman
PubMed: 34657398
DOI: 10.1002/epi4.12552 -
Zhongguo Dang Dai Er Ke Za Zhi =... Oct 2021To study the safety and efficacy of dexmedetomidine hydrochloride combined with midazolam in fiberoptic bronchoscopy in children. (Randomized Controlled Trial)
Randomized Controlled Trial
OBJECTIVES
To study the safety and efficacy of dexmedetomidine hydrochloride combined with midazolam in fiberoptic bronchoscopy in children.
METHODS
A total of 118 children who planned to undergo fiberoptic bronchoscopy from September 2018 to February 2021 were enrolled. They were divided into a control group (=60) and an observation group (=58) using a random number table. The observation group received intravenous pumping of dexmedetomidine hydrochloride (2 μg/mL) at 1 μg/kg and then intravenous injection of midazolam at 0.05 mg/kg, followed by dexmedetomidine hydrochloride pumped intravenously at 0.5-0.7 μg/(kg·h) 10 minutes later to maintain anesthesia. The control group was given intravenous pumping of propofol at 2 mg/kg and then intravenous injection of midazolam at 0.05 mg/kg, followed by propofol pumped intravenously at 4-6 mg/(kg·h) 10 minutes later to maintain anesthesia. Fiberoptic bronchoscopy was performed after the children were unconscious. Heart rate (HR), respiratory rate, blood oxygen saturation, and mean arterial pressure (MAP) were recorded before inserting the bronchoscope (T), at the time of inserting the bronchoscope (T), when the bronchoscope reached the glottis (T), when the bronchoscope reached the carina (T), and when the bronchoscope entered the bronchus (T). The intraoperative peak airway pressure (Ppeak), examination time, degree of sedation, extent of amnesia, incidence of adverse reactions, postoperative awakening time, and postoperative agitation score were also recorded.
RESULTS
Compared with the control group, the observation group had significantly decreased MAP at T to T and HR at T to T (<0.05). Compared with that at T, MAP was significantly increased at T to T in the control group and at T in the observation group (<0.05). HR was significantly higher at T to T than at T0 (<0.05). Compared with the control group, the observation group showed significantly lower intraoperative Ppeak value, incidence of intraoperative adverse reactions, and postoperative agitation score, significantly shorter examination time, and better effects of amnesia and anesthesia (<0.05). There was no significant difference in the degree of intraoperative sedation and postoperative awakening time between the two groups (>0.05).
CONCLUSIONS
Dexmedetomidine hydrochloride combined with midazolam is a safe and effective way to administer general anesthesia for fiberoptic bronchoscopy in children, which can ensure stable vital signs during examination, reduce intraoperative adverse reactions and postoperative agitation, shorten examination time, and increase amnesic effect.
Topics: Bronchi; Bronchoscopy; Child; Dexmedetomidine; Humans; Hypnotics and Sedatives; Midazolam; Prospective Studies
PubMed: 34719411
DOI: 10.7499/j.issn.1008-8830.2107075 -
The pharmacokinetics and pharmacodynamics of midazolam after intravenous administration to donkeys .Canadian Journal of Veterinary Research... Apr 2022The pharmacokinetics and pharmacodynamics of midazolam were studied in eight 1-to-3-year-old healthy gelded donkeys. Blood samples were obtained. Heart rate, respiratory...
The pharmacokinetics and pharmacodynamics of midazolam were studied in eight 1-to-3-year-old healthy gelded donkeys. Blood samples were obtained. Heart rate, respiratory rate, rectal temperature, sedation/excitement, ataxia, and response to tactile and auditory stimuli were recorded at baseline until 48 hours after intravenous (IV) midazolam (0.1 mg/kg) administration. Plasma midazolam and 1-hydroxymidazolam were measured using reversed-phase high-performance liquid chromatography. Pharmacokinetic variables were calculated using non-compartmental analysis. Physiologic data were analyzed using a mixed-effects model followed by Dunnett's test and behavioral data were analyzed using a Friedman test then a Dunn's test; < 0.05 was considered significant. Midazolam was detectable for up to 60 minutes post-treatment in 7 donkeys. The median total body clearance, volume of distribution at steady state, elimination half-life, and area under concentration-time profile were 1210 mL/kg/h, 359 mL/kg, 0.27 hours, and 82.7 h × ng/mL, respectively. 1-hydroxymidazolam was detected (29 to 105 ng/mL) between 5 to 15 minutes post-treatment in 4 donkeys. Compared to baseline, rectal temperature and ataxia increased from 90 to 720 minutes ( ≤ 0.038) and 3 to 15 minutes ( ≤ 0.024) post-treatment, respectively. No other parameters showed statistically significant differences. Healthy donkeys cleared midazolam rapidly from plasma after IV administration. Transient ataxia and recumbency without sedation were observed.
Topics: Administration, Intravenous; Animals; Ataxia; Equidae; Half-Life; Midazolam
PubMed: 35388227
DOI: No ID Found -
Journal of Pharmacy Practice Feb 2023The purpose of this drug review was to explore the safety and efficacy of the newly approved benzodiazepine, remimazolam, in order to evaluate its place in therapy. (Review)
Review
PURPOSE
The purpose of this drug review was to explore the safety and efficacy of the newly approved benzodiazepine, remimazolam, in order to evaluate its place in therapy.
SUMMARY
Remimazolam has a faster onset of action and recovery time than midazolam when given as single IV doses. Additionally, it has no known CYP450 interactions that would contribute to drug-drug interactions. Patients with severe hepatic impairment may require dose titration as well as the elderly who should be closely monitored. Although remimazolam vials should be protected from light and must be reconstituted immediately before use, the reconstituted vial may be stored for later use at room temperature for up to 8 hours. Remimazolam is more expensive than current options used in practice, as such individual institutional formulary and provider preference will require review to see if its advantages are worth the additional cost and to determine its place in therapy.
CONCLUSION
Remimazolam is a novel option when choosing a benzodiazepine for procedural sedation that has pharmacokinetic and pharmacodynamic advantages when compared to other commonly prescribed sedatives. Remimazolam has proved superior to midazolam when analyzing drug-drug interactions, onset, and time to alertness. Remimazolam also has a shorter elimination half-life and decreased volume of distribution when compared to midazolam.
Topics: Humans; Aged; Midazolam; Double-Blind Method; Benzodiazepines; Hypnotics and Sedatives
PubMed: 34155946
DOI: 10.1177/08971900211027303