Abstract:Context:Preoperative anxiety and uncooperativeness experienced by pediatric patients are commonly associated with postoperative behavioral problems.Aims:We aimed to evaluate the efficacy and safety of intranasal Midazolam as a sedative in a pediatric age group for radiological imaging procedures and to note onset of sedation, level of sedation, condition of patient during separation from parents and effect on the cardio-respiratory system.Settings and Design:Randomized double-blinded study.Subjects and Methods… Show more
“…The reported drowsiness and relaxation responses in this trial demonstrate that sedation via intranasal dosing with remimazolam is feasible, even with a non-optimized formulation. Onset times were faster than those typically reported for midazolam, which is used intranasally with some success, e.g., for imaging or in dental practices [ 11 – 15 ]. A limitation of the current trial design was the use of non-optimized IV formulation, resulting in the need to apply large volumes of either solution or powder in order to achieve clinical effects.…”
Purpose
Remimazolam is a novel and ultra-short-acting sedative currently developed for intravenous use in procedural sedation, general anesthesia, and ICU sedation. However, intravenous administration is not always appropriate, depending on the patient or setting. This study evaluated intranasal administration as a potential alternative route.
Methods
The study used a randomized, double-blind, 9 period cross-over design to compare the pharmacokinetics, pharmacodynamics, and safety of single intranasal doses of 10, 20, and 40 mg remimazolam (as powder or solution) with intranasal placebo and 4 mg intravenous remimazolam.
Results
Intranasal remimazolam powder had a consistent absolute bioavailability of approximately 50%; Tmax was 10 min; AUC and Cmax were dose-proportional. The higher doses of intranasal solution, however, resulted in decreasing bioavailability and loss of dose-proportionality in AUC and Cmax despite complete drug absorption due to partial swallowing of dose and the resulting first-pass effect. Pharmacodynamics were generally consistent with PK. Peak effects (drowsiness, relaxation, any, memory, response time) were in similar ranges after intranasal (10 to 40 mg) as intravenous (4 mg) dosing and were partially, but not consistently, dose-related. Safety results were generally consistent with other benzodiazepines; however, intranasal remimazolam (but not placebo) caused nasal discomfort/pain, in some cases even severe.
Conclusions
Intranasal administration of remimazolam was safe and caused sedative effects. However, the severe pain and discomfort caused by intranasal remimazolam prohibit its use by this route of administration, at least with the currently available intravenous formulation.
“…The reported drowsiness and relaxation responses in this trial demonstrate that sedation via intranasal dosing with remimazolam is feasible, even with a non-optimized formulation. Onset times were faster than those typically reported for midazolam, which is used intranasally with some success, e.g., for imaging or in dental practices [ 11 – 15 ]. A limitation of the current trial design was the use of non-optimized IV formulation, resulting in the need to apply large volumes of either solution or powder in order to achieve clinical effects.…”
Purpose
Remimazolam is a novel and ultra-short-acting sedative currently developed for intravenous use in procedural sedation, general anesthesia, and ICU sedation. However, intravenous administration is not always appropriate, depending on the patient or setting. This study evaluated intranasal administration as a potential alternative route.
Methods
The study used a randomized, double-blind, 9 period cross-over design to compare the pharmacokinetics, pharmacodynamics, and safety of single intranasal doses of 10, 20, and 40 mg remimazolam (as powder or solution) with intranasal placebo and 4 mg intravenous remimazolam.
Results
Intranasal remimazolam powder had a consistent absolute bioavailability of approximately 50%; Tmax was 10 min; AUC and Cmax were dose-proportional. The higher doses of intranasal solution, however, resulted in decreasing bioavailability and loss of dose-proportionality in AUC and Cmax despite complete drug absorption due to partial swallowing of dose and the resulting first-pass effect. Pharmacodynamics were generally consistent with PK. Peak effects (drowsiness, relaxation, any, memory, response time) were in similar ranges after intranasal (10 to 40 mg) as intravenous (4 mg) dosing and were partially, but not consistently, dose-related. Safety results were generally consistent with other benzodiazepines; however, intranasal remimazolam (but not placebo) caused nasal discomfort/pain, in some cases even severe.
Conclusions
Intranasal administration of remimazolam was safe and caused sedative effects. However, the severe pain and discomfort caused by intranasal remimazolam prohibit its use by this route of administration, at least with the currently available intravenous formulation.
The purpose of this study was to compare the efficacy of oral triclofos (TRI), intranasal midazolam (INM), and intranasal dexmedetomidine (IND) in achieving successful sedation in children undergoing MRI. This open-label, three-arm, randomized trial was conducted in a tertiary care teaching hospital over 18-month period. Children scheduled for MRI were enrolled. Rate of successful/adequate sedation was assessed using the Paediatric Sedation State Scale (PSSS). The primary outcome was the efficacy (successful sedation or sedation rate) of the three drugs. One-hundred and ninety-five children were included for the MRI procedure. IND was found to be superior in terms of achieving successful sedation. INM had a shorter onset and duration of sedation compared to IND and TRI, but with an increased failure rate (88.3%). Keeping INM as the reference group, it was found that the odds of sedation increased 4.1 times on changing from INM to IND (p < 0.01), and 2.26 times on changing from INM to TRI (p < 0.01). Adverse events included nasal discomfort (18.3%) in INM group; and self-limited tachycardia (4.6%) and hypotension (10.8%) in the IND group.Conclusion: IND was more efficacious than INM or TRI for procedural sedation in children undergoing MRI without any significant adverse events.
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