The Winner by a Nose: Intranasal Midazolam.
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SUBMITTER: Faught E
PROVIDER: S-EPMC6864572 | biostudies-literature | 2019 Sep
REPOSITORIES: biostudies-literature
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Project description:ObjectiveTo 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.MethodsIn 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.ResultsLatency 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. PaCO2t 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.Conclusions and clinical relevanceIN administration was as effective as IM administration in promoting safe chemical restraint, with minimal changes in homeostasis, with a shorter duration and latency period.
| S-EPMC11462642 | biostudies-literature
Project description:We determine whether aerosolized intranasal or buccal midazolam reduces the distress of pediatric laceration repair compared with oral midazolam.Children aged 0.5 to 7 years and needing nonparenteral sedation for laceration repair were randomized to receive oral, aerosolized intranasal, or aerosolized buccal midazolam. Patient distress was rated by blinded review of videotapes, using the Children's Hospital of Eastern Ontario Pain Score. Secondary outcomes included activity scores, sedation adequacy, sedation onset, satisfaction, and adverse events.For the 169 subjects (median age 3.1 years) evaluated for the primary outcome, we found significantly less distress in the buccal midazolam group compared with the oral route group (P=.04; difference -2; 95% confidence interval -4 to 0) and a corresponding nonsignificant trend for the intranasal route (P=.08; difference -1; 95% confidence interval -3 to 1). Secondary outcomes (177 subjects) favored the intranasal group, including a greater proportion of patients with an optimal activity score (74%), a greater proportion of parents wanting this sedation in the future, and faster sedation onset. Intranasal was the route least tolerated at administration. Adverse events were similar between groups.When comparing the administration of midazolam by 3 routes to facilitate pediatric laceration repair, we observed slightly less distress in the aerosolized buccal group. The intranasal route demonstrated a greater proportion of patients with optimal activity scores, greater proportions of parents wanting similar sedation in the future, and faster onset but was also the most poorly tolerated at administration. Aerosolized buccal or intranasal midazolam represents an effective and useful alternative to oral midazolam for sedation for laceration repair.
| S-EPMC3183391 | biostudies-literature
Project description:PurposeThe optimal sedative regime that provides the greatest comfort and the lowest risk for procedural sedation in young children remains to be determined. The aim of this randomized, blinded, controlled, parallel-design trial was to evaluate the efficacy of intranasal ketamine and midazolam as the main component of the behavioral guidance approach for preschoolers during dental treatment.Materials and methodsChildren under seven years of age, with caries and non-cooperative behavior, were randomized into three groups: (KMIN) intranasal ketamine and midazolam; (KMO) oral ketamine and midazolam; or (MO) oral midazolam. The dental sedation appointments were videotaped, and the videos were analyzed using the Ohio State University Behavioral Rating Scale (OSUBRS) to determine the success of the sedation in each group. Intra- and postoperative adverse events were recorded. Data analysis involved descriptive statistics and non-parametric tests (P < 0.05, IBM SPSS).ResultsParticipants were 84 children (28 per group; 43 boys), with a mean age of 3.1 years (SD 1.2). Children's baseline and the dental sedation session characteristics were balanced among groups. The success of the treatment as assessed by the dichotomous variable 'quiet behavior for at least 60% of the session length' was: KMIN 50.0% (n = 14; OR 2.10, 95% CI 0.71 to 6.30), KMO 46.4% (n = 13; OR 1.80, 95% CI 0.62 to 5.40), MO 32.1% (n = 9) (P = 0.360). Adverse events were minor, occurred in 37 of 84 children (44.0%), and did not differ among groups (P = 0.462).ConclusionAll three regimens provided moderate dental sedation with minor adverse events, with marked variability in the behavior of children during dental treatment. The potential benefit of the ketamine-midazolam combination should be further investigated in studies with larger samples.Trial registrationClinicalTrials.gov, identifier: NCT02447289. Registered on 11 May 2015, named "Midazolam and Ketamine Effect Administered Through the Nose for Sedation of Children for Dental Treatment (NASO)."
| S-EPMC6411109 | biostudies-literature
Project description:Study objectiveThe optimal intranasal volume of administration for achieving timely and effective sedation in children is unclear. We aimed to compare clinical outcomes relevant to procedural sedation associated with using escalating volumes of administration to administer intranasal midazolam.MethodsWe conducted a randomized, single-blinded, 3-arm, superiority clinical trial. Children aged 1 to 7 years and undergoing laceration repair requiring 0.5 mg/kg intranasal midazolam (5 mg/mL) were block-randomized to receive midazolam using 1 of 3 volumes of administration: 0.2, 0.5, or 1 mL. Procedures were videotaped, with outcome assessors blinded to volume of administration. Primary outcome was time to onset of minimal sedation (ie, score of 1 on the University of Michigan Sedation Scale). Secondary outcomes included procedural distress, time to procedure start, deepest level of sedation achieved, adverse events, and clinician and caregiver satisfaction.ResultsNinety-nine children were enrolled; 96 were analyzed for the primary outcome and secondary outcomes, except for the outcome of procedural distress, for which only 90 were analyzed. Time to onset of minimal sedation for each escalating volume of administration was 4.7 minutes (95% confidence interval [CI] 3.8 to 5.4 minutes), 4.3 minutes (95% CI 3.9 to 4.9 minutes), and 5.2 minutes (95% CI 4.6 to 7.0 minutes), respectively. There were no differences in secondary outcomes except for clinician satisfaction with ease of administration: fewer clinicians were satisfied when using a volume of administration of 0.2 mL.ConclusionThere was a slightly shorter time to onset of minimal sedation when a volume of administration of 0.5 mL was used compared with 1 mL, but all 3 volumes of administration produced comparable clinical outcomes. Fewer clinicians were satisfied with ease of administration with a volume of administration of 0.2 mL.
| S-EPMC5406242 | biostudies-literature
Project description:Background/purposeOptimal sedation management for pediatric dental treatment demands special focus as it's tubeless and shares a same oral space. The study was to evaluate dexmedetomidine compared to midazolam for intranasal premedication in pediatric dental treatment under intravenous deep sedation.Materials and methodsA hundred children aged 3-7 years scheduled for elective dental treatment under intravenous deep sedation anesthesia were enrolled, of whom 50 children (Group D) were intranasally premedicated with 2.0 μg/kg dexmedetomidine and the remaining 50 children (Group M) received traditional 0.2 mg/kg midazolam. Acceptance rate of venipuncture was regarded as the primary endpoint.ResultsThe acceptance rate of venipuncture in Group D and Group M were 76% versus 52%, respectively (P = 0.021). More children in Group M complained about bitter/sour taste than Group D (62% vs. 8%, P < 0.001). Intraoperatively, children in Group M were found to have more choking cough than Group D (30% vs. 9%, P = 0.003), and patients in Group M required more suction (18 [36%] in Group M vs. 4 [8%] in Group D, P = 0.001). There were no significant differences between the groups in the incidences of temporal hypoxemia (SpO2 ≤ 90%), however, two children in Group M experienced hypoxemia over 10 s.ConclusionCompared to the 0.2 mg/kg midazolam, children premedicated with 2.0 μg/kg intranasal dexmedetomidine showed superior venipuncture acceptance, had less intraoperative choking cough and required fewer suction. It seems to be a good alternative to midazolam as premedication for deep sedation in pediatric dental treatment.
| S-EPMC10829544 | biostudies-literature
Project description:BackgroundIntranasal midazolam and ketamine have been widely used as sedative premedication in children. It is difficult to determine which one yields better sedative effects for clinical practice. We conducted the present meta-analysis by summarizing the evidences to evaluate the efficacy and safety of intranasal midazolam versus intranasal ketamine as sedative premedication in pediatric patients.MethodsWe searched PubMed, Embase, and Cochrane Library from inception to April 2022. All randomized controlled trials (RCTs) used intranasal midazolam and ketamine as sedatives in children were enrolled. The risk of bias in RCTs was assessed by Cochrane risk of bias tool. Condition of parental separation, anesthesia induction or facemask acceptance, sedation level, different hemodynamic parameters and adverse events were considered as the outcomes in our study.ResultsA total of 16 studies with 1066 patients were enrolled. Compared with midazolam, administration of intranasal ketamine might be associated with severer changes in hemodynamics parameters including mean blood pressure (SMD = -0.53, with 95% CI [-0.93, -0.13]) and heart rate (HR) (SMD = -1.39, with 95% CI [-2.84, 0.06]). Meanwhile, administration of intranasal midazolam was associated with more satisfactory sedation level (61.76% vs 40.74%, RR = 1.53, with 95%CI [1.28, 1.83]), more rapid onset of sedation (SMD = -0.59, with 95%CI [-0.90, -0.28]) and more rapid recovery (SMD = -1.06, with 95%CI [-1.83, -0.28]). Current evidences also indicated that the differences of various adverse effects between two groups were not significant.ConclusionsGiven that administration of midazolam via intranasal route provides more satisfactory sedative level with less fluctuation of hemodynamics parameters and more rapid onset and recovery, it might be considered as the preferred sedative premedication for pediatric patients compared to ketamine. However, the widespread evidences with low or moderate quality indicated that superiority of intranasal midazolam in pediatric sedation needs to be confirmed by more studies with high quality and large sample size in future.Trial registrationThe protocol of present study was registered with PROSPERO (CRD42022321348).
| S-EPMC9773574 | biostudies-literature
Project description:Allopregnanolone, a positive modulator of GABAA receptors with antiseizure activity, has potential in the treatment of seizure emergencies. Instillation of allopregnanolone in 40% sulfobutylether-β-cyclodextrin into the nose in mice rapidly elevated the seizure threshold in the timed intravenous pentylenetetrazol (ED50, 5.6 mg/kg), picrotoxin (ED50, 5.9 mg/kg), and bicuculline seizure tests. The effect peaked at 15 min, decayed over 1 h, and was still evident in some experiments at 6 h. Intranasal allopregnanolone also delayed the onset of seizures in the maximal PTZ test. At an allopregnanolone dose (16 mg/kg) that conferred comparable effects on seizure threshold as the benzodiazepines midazolam and diazepam (both at doses of 1 mg/kg), allopregnanolone caused minimal sedation or motor toxicity in the horizontal screen test whereas both benzodiazepines produced marked behavioral impairment. In addition, intranasal allopregnanolone failed to cause loss-of-righting reflex in most animals, but when the same dose was administered intramuscularly, all animals became impaired. Intranasal allopregnanolone (10 mg/kg) caused a rapid increase in brain allopregnanolone with a Tmax of ~5 min after initiation of the intranasal delivery. High levels of allopregnanolone were recovered in the olfactory bulb (Cmax, 16,000 ng/mg) whereas much lower levels (Cmax, 670 ng/mg) were present in the remainder of the brain. We conclude that the unique ability of intranasal allopregnanolone to protect against seizures without inducing behavioral adverse effects is due in part to direct nose-to-brain delivery, with preferential transport to brain regions relevant to seizures. Benzodiazepines are commonly administered intranasally for acute seizure therapy, including for the treatment of acute repetitive seizures, but are not transported from nose-to-brain. Intranasal allopregnanolone acts with greater speed, has less propensity for adverse effects, and has the ability to overcome benzodiazepine refractoriness. This is the first study demonstrating rapid functional central nervous system activity of a nose-to-brain-delivered steroid. Intranasal delivery circumvents the poor oral bioavailability of allopregnanolone providing a route of administration permitting its evaluation as a treatment for diverse neuropsychiatric indications.
| S-EPMC8116426 | biostudies-literature
Project description:The coat color of mammals is determined by the melanogenesis pathway, which is responsible for maintaining the balance between black-brown eumelanin and yellow-reddish phaeomelanin. It is also believed that the color of the bovine nose is regulated in a similar manner; however, the molecular mechanism underlying pigment deposition in the black nose has yet to be elucidated. The aim of the present study was to identify melanogenesis-associated genes that are differentially expressed in the black vs. yellow nose of native Korean cows.
2013-12-26 | GSE53657 | GEO
Project description:ObjectiveThe objective of this study was to assess the efficacy and tolerability of intranasal midazolam (in-MDZ) administration for antiseizure treatment in adults.MethodsEmbase and Medline literature databases were searched. We included randomized trials and cohort studies (excluding case series) of adult patients (≥ 18 years of age) examining in-MDZ administration for epilepsy, epileptic seizures, or status epilepticus published in English between 1985 and 2022. Studies were screened for eligibility based on predefined criteria. The primary outcome was the efficacy of in-MDZ administration, and the secondary outcome was its tolerability. Extracted data included study design, patient characteristics, intervention details, and outcomes. Risk of bias was assessed using the Cochrane Risk of Bias Tool.ResultsA total of 12 studies with 929 individuals treated with in-MDZ were included. Most studies were retrospective, with their number increasing over time. Administered in-MDZ doses ranged from 2.5 to 20 mg per single dose. The mean proportion of successful seizure termination after first in-MDZ administration was 72.7% (standard deviation [SD] 18%), and the proportion of seizure recurrence or persistent seizures ranged from 61 to 75%. Most frequent adverse reactions to in-MDZ were dizziness (mean 23.5% [SD 38.6%]), confusion (one study; 17.4%), local irritation (mean 16.6% [SD 9.6%]), and sedation (mean 12.7% [SD 9.7%]).ConclusionsAdministration of in-MDZ seems promising for the treatment of prolonged epileptic seizures and seizure clusters in adults. Limited evidence suggests that intranasal administration is safe. Further research is warranted because of the heterogeneity of cohorts, the variation in dosages, and the lack of uniformity in defining successful seizure termination.
| S-EPMC11377482 | biostudies-literature
Project description:BackgroundMidazolam and α2-adrenoceptor agonists have been widely used off-label as intranasal sedatives for children. The present meta-analysis aimed to evaluate the effects of two interventions in pediatric sedation.MethodsPubMed, Embase, and Cochrane Library were searched from inception to April 2022. All randomized controlled trials used intranasal α2-adrenoceptor agonists and midazolam as sedatives in children were enrolled. Parental separation, anesthesia induction or facemask acceptance, sedation level, different hemodynamic parameters and adverse events were considered as outcomes.ResultsTotally 21 studies with 1,495 patients were included. Only one study reported comparison between midazolam and clonidine met the inclusion criteria, and patients in clonidine group had significantly better mask acceptance compared to midazolam group. Compared with midazolam, using of dexmedetomidine was associated with higher rate of satisfactory parental separation (52.88% vs 75.18%, RR = 0.70, with 95%CI [0.55, 0.90]), anesthesia induction or facemask acceptance (60.92% vs 81.47%, RR = 0.76, 95% CI [0.68, 0.84]) and less incidence of postoperative pain and nasal irritation.ConclusionCompared with midazolam, dexmedetomidine should be considered as the preferred intranasal sedative option for pediatric patients, since it provides more satisfactory sedative level with less incidence of several side effects. But insufficient evidences about effects of intranasal clonidine and overall low and moderate quality evidences evaluated by GRADE system indicate that superiority of intranasal α2-adrenoceptor agonists in pediatric sedation needs to be validated by more studies with high quality and large sample size in future.
| S-EPMC9928077 | biostudies-literature