Dataset Information

Two-center randomized controlled trial comparing oral chloral hydrate and intranasal combination of dexmedetomidine and ketamine for procedural sedation in children: study protocol.

ABSTRACT:

Background

Oral chloral hydrate is widely used in pediatric sedation. Intranasal dexmedetomidine has been increasingly used for pediatric sedation; however, its improvement is warranted. The combination of dexmedetomidine with ketamine can improve onset and hemodynamic stability while maintaining sedative efficacy. This study aims to determine the efficacy and safety of intranasal combination of dexmedetomidine and ketamine compared to oral chloral hydrate.

Methods

This is a prospective, parallel-arm, single-blinded, two-center, superiority randomized controlled trial with 1:1 allocation, designed to compare the effects of intranasal combination of dexmedetomidine and ketamine with those of oral chloral hydrate. We shall enroll 136 patients aged < 7 years old in this study. Prior to the procedure, we shall randomize each patient into the control group (oral chloral hydrate 50 mg/kg) or study group (intranasal dexmedetomidine 2 μg/kg and ketamine 3 mg/kg). The primary outcome will be the rate of achieving an adequate sedation level (6-point Pediatric Sedation State Scale 1, 2, or 3) within 15 min. In addition, we shall measure the sedation time, sedation failure rate, completion of procedure, adverse events, patient acceptance, and physician satisfaction.

Discussion

This study will provide evidence of the efficacy and safety of the intranasal combination of dexmedetomidine and ketamine in comparison with oral chloral hydrate.

Trial registration

ClinicalTrials.gov , NCT04820205. Registered on 19th March 2021.

SUBMITTER: Jang YE

PROVIDER: S-EPMC9808979 | biostudies-literature | 2023 Jan

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Two-center randomized controlled trial comparing oral chloral hydrate and intranasal combination of dexmedetomidine and ketamine for procedural sedation in children: study protocol.

Jang Young-Eun YE Joo Eun-Young EY Lee Ji-Hyun JH Kim Eun-Hee EH Kang Pyoyoon P Park Jung-Bin JB Kim Hee-Soo HS Kim Jin-Tae JT

Trials 20230103 1

<h4>Background</h4>Oral chloral hydrate is widely used in pediatric sedation. Intranasal dexmedetomidine has been increasingly used for pediatric sedation; however, its improvement is warranted. The combination of dexmedetomidine with ketamine can improve onset and hemodynamic stability while maintaining sedative efficacy. This study aims to determine the efficacy and safety of intranasal combination of dexmedetomidine and ketamine compared to oral chloral hydrate.<h4>Methods</h4>This is a prosp ...[more]

PMID: 36597163

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Project description:BackgroundTo evaluate the efficacy and safety of rectal chloral hydrate (CH) in pediatric procedural sedation.MethodsSeven electronic databases and 3 clinical trials registry platforms were searched, and the deadline was August 2022. Randomized controlled trials evaluating the efficacy and safety of rectal CH in pediatric procedural sedation were included by 2 reviewers. The extracted outcomes included the success rate of sedation, sedation latency, sedation duration, and adverse events. The Cochrane risk of bias tool was used to assess the risk of bias. The outcomes were analyzed using Review Manager 5.3 software.ResultsForty-four randomized controlled trials with 8007 children were included in the meta-analysis. The success rate of sedation in the rectal CH group was significantly higher than that in the placebo group (risk ratio [RR], 2.60 [95% confidence interval [CI], 1.74-3.89]; P < .01; RR, 1.24 [95% CI, 1.01-1.54]; P = .04), oral CH group (RR, 1.12 [95% CI, 1.09-1.14]; I2 = 36%; P < .001; number needed to treat [NNT] = 10), diazepam group (RR, 1.21 [95% CI, 1.10-1.33]; I2 = 0%; P < .001; NNT = 6), phenobarbital group (RR, 1.24 [95% CI, 1.13-1.35]; I2 = 12%; P < .001; NNT = 6), and ketamine group (RR, 1.39 [95% CI, 1.20-1.60]; I2 = 20%; P < .001; NNT = 5). There was no significant difference in the success rate of sedation between the rectal CH group and the midazolam group (RR, 0.98 [95% CI, 0.86-1.11]; I2 = 51%; P > .05). The sedation latency was significantly shorter in rectal CH group than that in the oral CH group (mean difference [MD], -6.36 [95% CI, -7.04 to -5.68]; I2 = 49%; P < .001) and the phenobarbital group (MD, -7.64 [95% CI, -9.12 to -6.16]; P < .00001). The sedation duration in the rectal CH group was significantly longer than in the oral CH group (MD, 6.43 [95% CI, 4.39-8.47]; I2 = 0%; P < .001). The overall incidence of adverse events was significantly lower with rectal CH than with oral CH (RR, 0.21 [95% CI, 0.16-0.29]; I2 = 45%; P < .001) and ketamine (RR, 0.26 [95% CI, 0.12-0.60]; I2 = 0%; P = .001). There was no significant difference in the overall incidence of adverse events with rectal CH compared with intramuscular midazolam (RR, 0.55 [95% CI, 0.23-1.28]; P = .17) and intranasal midazolam (RR, 3.00 [95% CI, 0.66-13.69]; P = .16).ConclusionThe available evidence suggests that rectal CH cloud be an effective and safe sedative agent for pediatric procedural sedation.

Project description:IntroductionUp to 40% of orthopaedic injuries in children require a closed reduction, almost always necessitating procedural sedation. Intravenous ketamine is the most commonly used sedative agent. However, intravenous insertion is painful and can be technically difficult in children. We hypothesise that a combination of intranasal dexmedetomidine plus intranasal ketamine (Ketodex) will be non-inferior to intravenous ketamine for effective sedation in children undergoing a closed reduction.Methods and analysisThis is a six-centre, four-arm, adaptive, randomised, blinded, controlled, non-inferiority trial. We will include children 4-17 years with a simple upper limb fracture or dislocation that requires sedation for a closed reduction. Participants will be randomised to receive either intranasal Ketodex (one of three dexmedetomidine and ketamine combinations) or intravenous ketamine. The primary outcome is adequate sedation as measured using the Paediatric Sedation State Scale. Secondary outcomes include length of stay, time to wakening and adverse effects. The results of both per protocol and intention-to-treat analyses will be reported for the primary outcome. All inferential analyses will be undertaken using a response-adaptive Bayesian design. Logistic regression will be used to model the dose-response relationship for the combinations of intranasal Ketodex. Using the Average Length Criterion for Bayesian sample size estimation, a survey-informed non-inferiority margin of 17.8% and priors from historical data, a sample size of 410 participants will be required. Simulations estimate a type II error rate of 0.08 and a type I error rate of 0.047.Ethics and disseminationEthics approval was obtained from Clinical Trials Ontario for London Health Sciences Centre and McMaster Research Ethics Board. Other sites have yet to receive approval from their institutions. Informed consent will be obtained from guardians of all participants in addition to assent from participants. Study data will be submitted for publication regardless of results.Trial registration numberNCT0419525.

Project description:BackgroundProcedural sedation and analgesia (PSA) is frequently required to perform closed reductions for fractures and dislocations in children. Intravenous (IV) ketamine is the most commonly used sedative agent for closed reductions. However, as children find IV insertion a distressing and painful procedure, there is need to identify a feasible alternative route of administration. There is evidence that a combination of dexmedetomidine and ketamine (ketodex), administered intranasally (IN), could provide adequate sedation for closed reductions while avoiding the need for IV insertion. However, there is uncertainty about the optimal combination dose for the two agents and whether it can provide adequate sedation for closed reductions. The Intranasal Dexmedetomidine Plus Ketamine for Procedural Sedation (Ketodex) study is a Bayesian phase II/III, non-inferiority trial in children undergoing PSA for closed reductions that aims to address both these research questions. This article presents in detail the statistical analysis plan for the Ketodex trial and was submitted before the outcomes of the trial were available for analysis.Methods/designThe Ketodex trial is a multicenter, four-armed, randomized, double-dummy controlled, Bayesian response adaptive dose finding, non-inferiority, phase II/III trial designed to determine (i) whether IN ketodex is non-inferior to IV ketamine for adequate sedation in children undergoing a closed reduction of a fracture or dislocation in a pediatric emergency department and (ii) the combination dose for IN ketodex that provides optimal sedation. Adequate sedation will be primarily measured using the Pediatric Sedation State Scale. As secondary outcomes, the Ketodex trial will compare the length of stay in the emergency department, time to wakening, and adverse events between study arms.DiscussionThe Ketodex trial will provide evidence on the optimal dose for, and effectiveness of, IN ketodex as an alternative to IV ketamine providing sedation for patients undergoing a closed reduction. The data from the Ketodex trial will be analyzed from a Bayesian perspective according to this statistical analysis plan. This will reduce the risk of producing data-driven results introducing bias in our reported outcomes.Trial registrationClinicalTrials.gov NCT04195256 . Registered on December 11, 2019.

Project description:BackgroundProcedural sedation and analgesia are commonly used in the Emergency Departments. Despite this common need, there is still a lack of options for adequate and safe analgesia and sedation in children. The objective of this study was to evaluate whether intranasal dexmedetomidine could provide more effective analgesia and sedation during a procedure than intranasal esketamine.MethodsThis was a double-blind equally randomized (1:1) superiority trial of 30 children aged 1-3 years presenting to the Emergency Department with a laceration or a burn and requiring procedural sedation and analgesia. Patients were randomized to receive 2.0 mcg/kg intranasal dexmedetomidine or 1.0 mg/kg intranasal esketamine. The primary outcome measure was highest pain (assessed using Face, Legs, Activity, Cry, Consolability scale (FLACC)) during the procedure. Secondary outcomes were sedation depth, parents' satisfaction, and physician's assessment. Comparisons were done using Mann-Whitney U test (continuous variables) and Fisher's test (categorical variables).ResultsAdequate analgesia and sedation were reached in 28/30 patients. The estimated sample size was not reached due to changes in treatment of minor injuries and logistical reasons. The median (IQR) of highest FLACC was 1 (0-3) with intranasal dexmedetomidine and 5 (2-6.75) with intranasal esketamine, (p-value 0.09). 85.7% of the parents with children treated with intranasal dexmedetomidine were "very satisfied" with the procedure and sedation compared to the 46.2% of those with intranasal esketamine, (p-value 0.1). No severe adverse events were reported during this trial.ConclusionsThis study was underpowered and did not show any difference between intranasal dexmedetomidine and intranasal esketamine for procedural sedation and analgesia in young children. However, the results support that intranasal dexmedetomidine could provide effective analgesia and sedation during procedures in young children aged 1-3 years with minor injuries.Trial registrationEudra-CT 2017-00057-40, April 20, 2017. https://eudract.ema.europa.eu/.

Project description:BackgroundProcedural sedation and analgesia is an important part of pediatric emergency care, safe and clinically useful alternatives for adequate management are necessary. The objective of this clinical trial was to evaluate the non-inferiority of intranasal dexmedetomidine to nitrous oxide with respect to analgesia for a painful procedure in children 3-15 years of age.MethodsThis prospective, equally randomized, open-label, non-inferiority trial was conducted at a Pediatric Emergency Department. Previously healthy children 3-15 years of age, with an extremity fracture or luxation or a burn and requiring procedural sedation and analgesia were eligible. Patients were randomized to receive either intranasal dexmedetomidine or inhaled nitrous oxide. The primary outcome measure was highest pain level during the procedure, assessed with Face, Legs, Activity, Cry, Consolability scale (FLACC). Mann-Whitney U test (continuous variables) and Fisher's test (categorical variables) were used for statistical analysis.ResultsThe highest FLACC was median 4 (IQR 3-6) with intranasal dexmedetomidine and median 4 (IQR 2-6) with nitrous oxide. The median of the difference between samples from each group for FLACC was 0 with 95%CI (0-1), thus intranasal dexmedetomidine was not inferior to nitrous oxide with respect to the level of pain during the procedure. The same method for procedural sedation and analgesia would be accepted by 52/74 (82.5%) children and 65/74 (91.5%) parents in the intranasal dexmedetomidine group respectively 59/74 (88.1%) versus 70/74 (94.6%) with nitrous oxide. No serious adverse events were reported.ConclusionsThe results of this trial support that intranasal dexmedetomidine is not inferior to 50% nitrous oxide in providing analgesia for a painful procedure in children 3-15 years of age and can be considered as an alternative to 50% nitrous oxide for procedural sedation and analgesia.Trial registrationEudraCT 201,600,377,317, April 20, 2017. https://eudract.ema.europa.eu/ .

Dataset Information

Two-center randomized controlled trial comparing oral chloral hydrate and intranasal combination of dexmedetomidine and ketamine for procedural sedation in children: study protocol.

Background

Methods

Discussion

Trial registration

Publications

Two-center randomized controlled trial comparing oral chloral hydrate and intranasal combination of dexmedetomidine and ketamine for procedural sedation in children: study protocol.

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