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

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.

Pediatric Sedation in the Emergency Department: Trends from a Nationwide Population-based Study in Korea, 2007-2018.

BACKGROUND: Pediatric sedation in the emergency department (ED) is widely performed in Korea; thus exploring the trends of its use is necessary. This study aimed to investigate the characteristics of patients and sedatives use in the ED and verify their changes over recent years. METHODS: A nationwide population-based retrospective study was conducted including pediatric patients aged ≤ 15 years who received sedative medication in the ED and were discharged during 2007-2018, using the Korean Health Insurance Review and Assessment Service database. Patient characteristics (age, sex, level of ED, and diagnosis) and type of sedative used were analyzed. RESULTS: Sedation was performed in total 468,221 visits during 2007-2018 (399,320 visits, at least 3.8% of overall ED visits during 2009-2018). Among these, 71.0% were children aged 1-3 years and 93.5% were sedated to support diagnosis of injury. An increase in total sedation was observed in patients aged 4-6 years during the study period (from 13.8% to 21.8%). A gradual decrease in the use of chloral hydrate (CH) compared with an increase in ketamine use was observed (CH, from 70.6% to 28.6%; ketamine, from 23.8% to 60.7%). Therefore, ketamine was the most used sedative since 2014. The most frequently used sedatives over the study period differed according to age groups (CH in <1 year and 1-3 years; ketamine in 4-6 years and 7-10 years; and midazolam in 11-15 years). CONCLUSIONS: The characteristics of patients related to sedatives use in the ED have changed over time. These changes should be considered in the development of future Korean guidelines regarding pediatric sedation in the ED.

Chloral hydrate as a sedating agent for neurodiagnostic procedures in children.

BACKGROUND: This is an updated version of a Cochrane Review published in 2017. Paediatric neurodiagnostic investigations, including brain neuroimaging and electroencephalography (EEG), play an important role in the assessment of neurodevelopmental disorders. The use of an appropriate sedative agent is important to ensure the successful completion of the neurodiagnostic procedures, particularly in children, who are usually unable to remain still throughout the procedure. OBJECTIVES: To assess the effectiveness and adverse effects of chloral hydrate as a sedative agent for non-invasive neurodiagnostic procedures in children. SEARCH METHODS: We searched the following databases on 14 May 2020, with no language restrictions: the Cochrane Register of Studies (CRS Web) and MEDLINE (Ovid, 1946 to 12 May 2020). CRS Web includes randomised or quasi-randomised controlled trials from PubMed, Embase, ClinicalTrials.gov, the World Health Organization International Clinical Trials Registry Platform, the Cochrane Central Register of Controlled Trials (CENTRAL), and the specialised registers of Cochrane Review Groups including Cochrane Epilepsy. SELECTION CRITERIA: Randomised controlled trials that assessed chloral hydrate agent against other sedative agent(s), non-drug agent(s), or placebo. DATA COLLECTION AND ANALYSIS: Two review authors independently evaluated studies identified by the search for their eligibility, extracted data, and assessed risk of bias. Results were expressed in terms of risk ratio (RR) for dichotomous data and mean difference (MD) for continuous data, with 95% confidence intervals (CIs). MAIN RESULTS: We included 16 studies with a total of 2922 children. The methodological quality of the included studies was mixed. Blinding of the participants and personnel was not achieved in most of the included studies, and three of the 16 studies were at high risk of bias for selective reporting. Evaluation of the efficacy of the sedative agents was also underpowered, with all the comparisons performed in small studies. Fewer children who received oral chloral hydrate had sedation failure compared with oral promethazine (RR 0.11, 95% CI 0.01 to 0.82; 1 study; moderate-certainty evidence). More children who received oral chloral hydrate had sedation failure after one dose compared to intravenous pentobarbital (RR 4.33, 95% CI 1.35 to 13.89; 1 study; low-certainty evidence), but there was no clear difference after two doses (RR 3.00, 95% CI 0.33 to 27.46; 1 study; very low-certainty evidence). Children with oral chloral hydrate had more sedation failure compared with rectal sodium thiopental (RR 1.33, 95% CI 0.60 to 2.96; 1 study; moderate-certainty evidence) and music therapy (RR 17.00, 95% CI 2.37 to 122.14; 1 study; very low-certainty evidence). Sedation failure rates were similar between groups for comparisons with oral dexmedetomidine, oral hydroxyzine hydrochloride, oral midazolam and oral clonidine. Children who received oral chloral hydrate had a shorter time to adequate sedation compared with those who received oral dexmedetomidine (MD -3.86, 95% CI -5.12 to -2.6; 1 study), oral hydroxyzine hydrochloride (MD -7.5, 95% CI -7.85 to -7.15; 1 study), oral promethazine (MD -12.11, 95% CI -18.48 to -5.74; 1 study) (moderate-certainty evidence for three aforementioned outcomes), rectal midazolam (MD -95.70, 95% CI -114.51 to -76.89; 1 study), and oral clonidine (MD -37.48, 95% CI -55.97 to -18.99; 1 study) (low-certainty evidence for two aforementioned outcomes). However, children with oral chloral hydrate took longer to achieve adequate sedation when compared with intravenous pentobarbital (MD 19, 95% CI 16.61 to 21.39; 1 study; low-certainty evidence), intranasal midazolam (MD 12.83, 95% CI 7.22 to 18.44; 1 study; moderate-certainty evidence), and intranasal dexmedetomidine (MD 2.80, 95% CI 0.77 to 4.83; 1 study, moderate-certainty evidence). Children who received oral chloral hydrate appeared significantly less likely to complete neurodiagnostic procedure with child awakening when compared with rectal sodium thiopental (RR 0.95, 95% CI 0.83 to 1.09; 1 study; moderate-certainty evidence). Chloral hydrate was associated with a higher risk of the following adverse events: desaturation versus rectal sodium thiopental (RR 5.00, 95% 0.24 to 102.30; 1 study), unsteadiness versus intranasal dexmedetomidine (MD 10.21, 95% CI 0.58 to 178.52; 1 study), vomiting versus intranasal dexmedetomidine (MD 10.59, 95% CI 0.61 to 185.45; 1 study) (low-certainty evidence for aforementioned three outcomes), and crying during administration of sedation versus intranasal dexmedetomidine (MD 1.39, 95% CI 1.08 to 1.80; 1 study, moderate-certainty evidence). Chloral hydrate was associated with a lower risk of the following: diarrhoea compared with rectal sodium thiopental (RR 0.04, 95% CI 0.00 to 0.72; 1 study), lower mean diastolic blood pressure compared with sodium thiopental (MD 7.40, 95% CI 5.11 to 9.69; 1 study), drowsiness compared with oral clonidine (RR 0.44, 95% CI 0.30 to 0.64; 1 study), vertigo compared with oral clonidine (RR 0.15, 95% CI 0.01 to 2.79; 1 study) (moderate-certainty evidence for aforementioned four outcomes), and bradycardia compared with intranasal dexmedetomidine (MD 0.17, 95% CI 0.05 to 0.59; 1 study; high-certainty evidence). No other adverse events were significantly associated with chloral hydrate, although there was an increased risk of combined adverse events overall (RR 7.66, 95% CI 1.78 to 32.91; 1 study; low-certainty evidence). AUTHORS' CONCLUSIONS: The certainty of evidence for the comparisons of oral chloral hydrate against several other methods of sedation was variable. Oral chloral hydrate appears to have a lower sedation failure rate when compared with oral promethazine. Sedation failure was similar between groups for other comparisons such as oral dexmedetomidine, oral hydroxyzine hydrochloride, and oral midazolam. Oral chloral hydrate had a higher sedation failure rate when compared with intravenous pentobarbital, rectal sodium thiopental, and music therapy. Chloral hydrate appeared to be associated with higher rates of adverse events than intranasal dexmedetomidine. However, the evidence for the outcomes for oral chloral hydrate versus intravenous pentobarbital, rectal sodium thiopental, intranasal dexmedetomidine, and music therapy was mostly of low certainty, therefore the findings should be interpreted with caution. Further research should determine the effects of oral chloral hydrate on major clinical outcomes such as successful completion of procedures, requirements for an additional sedative agent, and degree of sedation measured using validated scales, which were rarely assessed in the studies included in this review. The safety profile of chloral hydrate should be studied further, especially for major adverse effects such as oxygen desaturation.

Rectal chloral hydrate sedation for computed tomography in young children with head trauma.

ABSTRACT: Children evaluated in the emergency department for head trauma often undergo computed tomography (CT), with some uncooperative children requiring pharmacological sedation. Chloral hydrate (CH) is a sedative that has been widely used, but its rectal use for child sedation after head trauma has rarely been studied. The objective of this study was to document the safety and efficacy of rectal CH sedation for cranial CT in young children.We retrospectively studied all the children with head trauma who received rectal CH sedation for CT in the emergency department from 2016 to 2019. CH was administered rectally at a dose of 50 mg/kg body weight. When sedation was achieved, CT scanning was performed, and the children were monitored until recovery. The sedative safety and efficacy were analyzed.A total of 135 children were enrolled in the study group, and the mean age was 16.05 months. The mean onset time was 16.41 minutes. Successful sedation occurred in 97.0% of children. The mean recovery time was 71.59 minutes. All of the vital signs were within normal limits after sedation, except 1 (0.7%) with transient hypoxia. There was no drug-related vomiting reaction in the study group. Adverse effects occurred in 11 patients (8.1%), but all recovered completely. Compared with oral CH sedation, rectal CH sedation was associated with quicker onset (P < .01), higher success rate (P < .01), and lower adverse event rate (P < .01).Rectal CH sedation can be a safe and effective method for CT imaging of young children with head trauma in the emergency department.

Intranasal dexmedetomidine versus oral chloral hydrate for diagnostic procedures sedation in infants and toddlers: A systematic review and meta-analysis.

BACKGROUND: Intranasal dexmedetomidine is a relatively new way to sedate young children undergoing nonpainful diagnostic procedures. We performed a meta-analysis to compare the efficacy and safety of intranasal dexmedetomidine in young children with those of oral chloral hydrate, which has been a commonly used method for decades. METHODS: We searched PubMed, Embase, and the Cochrane Library for all randomized controlled trials that compared intranasal dexmedetomidine with oral chloral hydrate in children undergoing diagnostic procedures. Data on success rate of sedation, onset time, recovery time, and adverse effects were extracted and respectively analyzed. RESULTS: Five studies with a total of 720 patients met the inclusion criteria. Intranasal dexmedetomidine provided significant higher success rate of sedation (relative risk [RR], 1.12; 95% confidence interval [CI], 1.02 to 1.24; P = .02; I = 74%) than oral chloral hydrate. Furthermore, it experienced significantly shorter onset time (weight mean difference [WMD], -1.79; 95% CI, -3.23 to -0.34; P = .02; I = 69%). Nevertheless, there were no statistically differences in recovery time (WMD, -10.53; 95% CI, -24.17 to 3.11; P = .13; I = 92%) and the proportion of patients back to normal activities (RR, 1.11; 95% CI, 0.77-1.60; P = .57; I = 0%). Intranasal dexmedetomidine was associated with a significantly lower incidence of nausea and vomiting (RR, 0.05; 95% CI, 0.01-0.22; P < .0001; I = 0%) than oral chloral hydrate. Although adverse events such as bradycardia, hypotension and hypoxia were not synthetized due to lack of data, no clinical interventions except oxygen supplementation were required in any patients. CONCLUSION: Our meta-analysis revealed that intranasal dexmedetomidine is possibly a more effective and acceptable sedation method for infants and toddlers undergoing diagnostic procedures than oral chloral hydrate. Additionally, it shows similar safety profile and could be a potential alternative to oral chloral hydrate.

Intramuscular dexmedetomidine and oral chloral hydrate for pediatric sedation for electroencephalography: A propensity score-matched analysis.

BACKGROUND: Intramuscular dexmedetomidine can be used for pediatric sedation without requiring intravenous access and has advantages for electroencephalography by inducing natural sleep pathway, but only a limited number of studies compared the efficacy of intramuscular dexmedetomidine with oral chloral hydrate. AIMS: To compare the efficacy and safety of intramuscular dexmedetomidine and oral chloral hydrate used for sedation during electroencephalography in pediatric patients. METHODS: We reviewed the medical records of pediatric patients who underwent sedation for electroencephalography between January 2015 and December 2016. Initial doses of dexmedetomidine and chloral hydrate were 3 mcg/kg and 50 mg/kg, respectively; second doses (1 mcg/kg and 50 mg/kg, respectively) were administered if adequate sedation was not achieved. Demographic data, time of sedative administration, time of sedation and awakening, and time of arrival at recovery room and discharge were analyzed. RESULTS: Out of a total of 1239 patients, 125 patients had received dexmedetomidine and 1114 had received chloral hydrate. After 1:1 propensity score matching, the dexmedetomidine and chloral hydrate groups each had 118 patients. Testing completion rate with a single dose of medication was higher in the dexmedetomidine group (91.5% vs 71.2%; mean difference [95% CI] 20.3 [10.8-29.9]; P < .0001; Pearson chi-square value = 16.09). Sedation onset time was shorter in the dexmedetomidine group as well (16.6 ± 13.0 minutes vs 41.5 ± 26.8 minutes; mean difference [95% CI] 24.8 [19.1-30.6]; P < .0001; T = 8.27). On the contrary, the duration of recovery was longer in the dexmedetomidine group (35.5 ± 40.2 minutes vs 18.5 ± 30.7 minutes; mean difference [95% CI] 18.6 [8.8-28.5]; P = .0002; T = -2.82). Total residence time was not significantly different between the two groups (125.8 ± 40.6 minutes vs 122.1 ± 42.2 minutes, mean difference [95% CI] 5.21 [6.1-16.5], P = .3665 T = 0.04). CONCLUSIONS: Intramuscular dexmedetomidine showed higher sedation success rate and shorter time to achieving the desired sedation level compared with oral chloral hydrate and thus may be an effective alternative for oral chloral hydrate in pediatric patients requiring sedation for electroencephalography.

Intranasal Dexmedetomidine for Procedural Distress in Children: A Systematic Review.

CONTEXT: Intranasal dexmedetomidine (IND) is an emerging agent for procedural distress in children. OBJECTIVE: To explore the effectiveness of IND for procedural distress in children. DATA SOURCES: We performed electronic searches of Medline (1946-2019), Embase (1980-2019), Google Scholar (2019), Cumulative Index to Nursing and Allied Health Literature (1981-2019), and Cochrane Central Register. STUDY SELECTION: We included randomized trials of IND for procedures in children. DATA EXTRACTION: Methodologic quality of evidence was evaluated by using the Cochrane Collaboration's risk of bias tool and the Grading of Recommendations Assessment, Development, and Evaluation system, respectively. The primary outcome was the proportion of participants with adequate sedation. RESULTS: Among 19 trials (N = 2137), IND was superior to oral chloral hydrate (3 trials), oral midazolam (1 trial), intranasal midazolam (1 trial), and oral dexmedetomidine (1 trial). IND was equivalent to oral chloral hydrate (2 trials), intranasal midazolam (2 trials), and intranasal ketamine (3 trials). IND was inferior to oral ketamine and a combination of IND plus oral ketamine (1 trial). Higher doses of IND were superior to lower doses (4 trials). Adverse effects were reported in 67 of 727 (9.2%) participants in the IND versus 98 of 591 (16.6%) in the comparator group. There were no reports of adverse events requiring resuscitative measures. LIMITATIONS: The adequacy of sedation was subjective, which possibly led to biased outcome reporting. CONCLUSIONS: Given the methodologic limitations of included trials, IND is likely more effective at sedating children compared to oral chloral hydrate and oral midazolam. However, this must be weighed against the potential for adverse cardiovascular effects.

Efficacy of chloral hydrate oral solution for sedation in pediatrics: a systematic review and meta-analysis.

OBJECTIVE: Chloral hydrate (CH), as a sedation agent, is widely used in children for diagnostic or therapeutic procedures. However, it has not come into the market and is currently only used as hospital preparation in China. This review aims to systematically evaluate the efficacy of CH in children of all age groups for sedation before medical procedures. MATERIALS AND METHODS: Seven electronic databases and three clinical trial registry platforms were searched and the deadline was September 2018. Randomized controlled trials (RCTs) evaluating the efficacy of CH for sedation in children were included by two reviewers. The extracted information included success rate of sedation, sedation latency and sedation duration. The Cochrane risk of bias tool was applied to assess the risk of bias. The outcomes were analyzed by Review Manager 5.3 software and expressed as relative risks (RR) or Mean Difference (MD) with 95% confidence interval (CI). Heterogeneity was assessed with I-squared (I2) statistics. RESULTS: A total of 24 RCTs involving 3564 children of CH for sedation were included in the meta-analysis. Compared to placebo group, CH group had a significant increase in success rate of sedation when used for painless and painful procedure (RR=4.15, 95% CI [1.21, 14.24], P=0.02; RR=1.28, 95% CI [1.17, 1.40], P<0.01), which included 22 and 455 children for this analysis, respectively. Compared to midazolam group, CH group had a significant increase in success rate of sedation (RR=1.63, 95% CI [1.48, 1.79], I2=0%, P<0.00001), sedation latency (MD=13.29, 95% CI [11.42, 15.16], I2=0%, P<0.00001) and sedation duration (MD=17.52, 95% CI [10.3, 24.71], I2=0%, P<0.05), which included 1052, 710 and 727 children for this analysis, respectively. Compared to diazepam, there was no significant difference in success rate of sedation (RR=0.93, 95% CI [0.80, 1.08], I2=52%, P=0.32), which included 230 children for this analysis. Compared to dexmedetomidine, there was no significant difference in the success rate of sedation (RR=0.92, 95% CI [0.80, 1.06], I2=48%, P=0.27) and sedation latency (RR=-1.09, 95% CI [-2.45, 0.26], I2=26%, P=0.11), which included 512 and 371 children for this analysis, respectively. Compared to barbiturates, there was no significant difference in the success rate of sedation (RR=1.03, 95% CI [0.94, 1.13], I2=50%, P=0.58) and sedation duration (MD=-0.72, 95% CI [-1.78, 0.34], I2=38%, P=0.18), which included 749 and 210 children for this analysis, respectively. CONCLUSIONS: From the extrapolation of the existing literature, CH oral solution is an appropriate effective alternative for sedation in pediatrics.

Comparison of intranasal midazolam, intranasal ketamine, and oral chloral hydrate for conscious sedation during paediatric echocardiography: results of a prospective randomised study.

OBJECTIVE: There are several agents used for conscious sedation by various routes in children. The aim of this prospective randomised study is to compare the effectiveness of three commonly used sedatives: intranasal ketamine, intranasal midazolam, and oral chloral hydrate for children undergoing transthoracic echocardiography. METHODS: Children who were referred to paediatric cardiology due to a heart murmur for transthoracic echocardiography were prospectively randomised into three groups. Seventy-three children received intranasal midazolam (0.2 mg/kg), 72 children received intranasal ketamine (4 mg/kg), and 72 children received oral chloral hydrate (50 mg/kg) for conscious sedation. The effects of three agents were evaluated in terms of intensity, onset, and duration of sedation. Obtaining high-quality transthoracic echocardiography images (i.e. absence of artefacts) were regarded as successful sedation. Side effects due to medications were also noted. RESULTS: There was no statistical difference in terms of sedation success rates between three groups (95.9, 95.9, and 94.5%, respectively). The median onset of sedation in the midazolam, ketamine, and chloral hydrate was 14 minutes (range 7-65), 34 minutes (range 12-56), and 40 minutes (range 25-57), respectively (p < 0.001 for all). However, the median duration of sedation in study groups was 68 minutes (range 20-75), 55 minutes (range 25-75), and 61 minutes (range 34-78), respectively (p = 0.023, 0.712, and 0.045). Gastrointestinal side effects such as nausea and vomiting were significantly higher in the chloral hydrate group (11.7 versus 0% for midazolam and 2.8% for ketamine, respectively, p = 0.002). CONCLUSION: Results of our prospectively randomised study indicate that all three agents provide adequate sedation for successful transthoracic echocardiography. When compared the three sedatives, intranasal midazolam has a more rapid onset of sedation while intranasal ketamine has a shorter duration of sedation. Intranasal ketamine can be used safely with fewer side effects in children undergoing transthoracic echocardiography.

Safety and effectiveness of chloral hydrate in outpatient paediatric sedation for objective hearing tests.

OBJECTIVES: Chloral hydrate is a sedative that has been used for many years in clinical practice and, under proper conditions, gives a deep and long enough sleep to allow performance of objective hearing tests in young children. The reluctance to use this substance stems from side effects reported over time that can vary, depending on dose, procedure settings and immediate life supporting intervention when needed. Our study adds to those that have appeared in recent years, showing that chloral hydrate is an effective and safe substance when is used in proper conditions. METHODS: The study included 322 children who needed sedation for objective hearing tests, from April 2014 to March 2018. Parents were instructed to bring the child tired and fasted for at least 2 h before sedation. The sedative was administered by trained staff in the hospital, and the child was monitored until awaking. RESULTS: In our study group, over half of the children were in the age 1-4 years group, and only 15% were older than 4 years. The dose of chloral hydrate ranged between 50 and 83 mg/kg body weight, with an average of 75 mg. Successful sedation occurred in 94.1% of children; 0.9% of children awoke during testing and required supplemental sedation or rescheduling of the testing. The most common side effects were vomiting, agitation, prolonged sleep, and failure to fall asleep. CONCLUSIONS: Comparing the side effects of chloral hydrate in our study with those from other studies, ours were similar to those described in the literature. In our study chloral hydrate was effective and had only limited adverse effects. The use of chloral hydrate under hospital conditions with proper monitoring could be a practical and safe solution for outpatients or those with short-term hospitalisation.

Successful paediatric renography does not require sedation.

INTRODUCTION: Sedation is often used to optimise ren-ography in children < 3 years, but it requires continuous monitoring. METHODS: We discontinued routine use of chloral hydrate sedation of patients undergoing renography, and introduced that children < 2 years were placed in a child immobiliser for nuclear examinations at the Department of Paediatrics before being transported for renography. In addition, children < 3 years were offered melatonin, which is not a sedative. Chloral hydrate was given only if parents wanted sedation. We analysed the results from a consecutive series of patients undergoing renography from August 2010 to December 2015 and compared data from those who had been administered choral hydrate sedation with those who had received no sedation. RESULTS: Renography was unaccomplished in 10% (3/30) of the choral hydrated sedated children and in 11% (54/512) of the non-sedated children (p = 0.83). Uncooperative children resulted in failed renography in 0% (0/3) and 39% (21/54) of cases, respectively (p = 0.46). Patients placed in a child immobiliser at the Department of Paediatrics had the greatest probability of achieving successful renography (p = 0.0013), the shortest renography procedure duration irrespective of melatonin use (p = 0.0001) and the lowest risk of a procedure duration > 60 minutes (p = 0.0004). CONCLUSIONS: Renography can be performed without sedation. We recommend that children < 2 years be placed in a child immobiliser at the Department of Paediatrics before being transported for renography. Additional studies are needed to investigate the effects of melatonin. FUNDING: none. TRIAL REGISTRATION: not relevant.

[Determination of hearing thresholds in children using auditory brainstem responses : Influence of sedation and anaesthesia on quality and measurement time]. / Hörschwellenbestimmungen bei Kindern mittels früher akustisch evozierter Potenziale : Einfluss von Sedierung und Narkose auf Qualität und Messzeit.

BACKGROUND: A fundamental prerequisite for successful application of auditory brainstem responses (ABR) in paedaudiological diagnostics is to ensure a high quality of the measurement. This is commonly quantified by means of the residual noise. Key factors are the averaging number and the magnitude of spontaneous electroencephalogram (EEG). This is the first study to quantify the influence of different forms of sedation (anaesthesia, sedation with chloral hydrate or melatonin, natural sleep) on the individual EEG magnitude in children. MATERIALS AND METHODS: ABR measurements of 80 children aged between 1 month and 6 years were analysed retrospectively. Individual mean EEG amplitude was calculated from the averaging number and the residual noise. The results were analysed statistically with the type of sedation as a factor. From the mean EEG amplitudes, a theoretical recording time for a residual noise level of 35 nV was estimated. RESULTS: The spontaneous EEG activity is, on average, 2.5-times larger in awake children than in naturally sleeping children and more than 4­times larger than in sedated children. Although the EEG amplitude in intubation anaesthesia was smaller than with the other three types of sedation, this difference was not significant. The theoretical measurement time for 35 nV of residual noise was 10-times larger in awake than in sedated children. CONCLUSION: The large difference in spontaneous EEG activity between awake and sedated children indicates that sedation should be used for estimation of hearing thresholds on the basis of ABR. Only in rare cases is a reliable estimate of hearing thresholds likely to be obtained from ABR in awake children. Since different types of sedation do not influence the measurement time significantly, selection can be made solely on the basis of age and medical indication.

Current sedation practices in paediatric audiology clinics in gauteng, South Africa.

AIM: The aim was to describe the current practices in sedation during AEP testing in infants and young children in Gauteng. METHODS: An exploratory qualitative research design was employed, where telephonic and face-to face interviews were conducted with 48 participants in paediatric audiology clinics that have AEP testing facilities in Gauteng, South Africa. Qualitative analysis was done, with inductive thematic analysis used for open ended questions. RESULTS: Findings revealed that 38% of the participants, majority of which were testing children under the age of 2 years, utilised natural sleep during testing, with only 29% utilizing conscious sedation. While all participants ensured pre-procedure fasting, findings revealed that 83% did not have or were unsure about the availability of monitoring methods, 63% had no emergency equipment, while 67% had no recovery and discharge criteria in their clinics. Conscious sedation at the outpatient clinic was mostly conducted by a registered nurse/an Ear, Nose & Throat specialist, with the anaesthesiologist serving in this role for AEP testing in theatre under general anaesthesia. Oral chloral hydrate and promethazine are the most commonly used medications, with melatonin also listed for conscious sedation. Propofol is the most commonly used for AEP testing in theatre. Three challenges were identified and these add to the implications raised by current findings. CONCLUSION: Current findings have implications for audiological assessment of the difficult-to-test population in this context; with a need for resource availability and access deliberations highlighted.

Short-term effects of single-dose chloral hydrate on neonatal auditory perception: An auditory event-related potential study.

OBJECTIVE: To study the short-term effects of a single-dose chloral hydrate on neonatal auditory perception by measuring auditory event-related potentials (aERPs). METHODS: Thirty-nine full-term neonates, aged 2-28 days and weighing 2980-4350 g, were divided into two groups including a chloral hydrate group (CH group, n = 17) and a non-chloral hydrate control group (non-CH group, n = 22). The CH group was given single-dose chloral hydrate (30 mg/kg) orally before aERPs measurement. An auditory oddball paradigm was used to elicit aERPs. P2 and N2 components of the ERP were recorded from electrodes at the Fz and Cz locations, and the areas under their curves (P2 and N2 areas) were calculated for the comparison between two groups. RESULTS: Significant differences was found in the P2 area between the two groups at Fz and Cz (Fz: F (1,37) = 487.75, P < 0.05; Cz: F (1,37) = 1465.94, P < 0.05). Similarly, significant difference was also in the N2 area between the two groups at both locations (Fz: F(1,37) = 153.38, P < 0.05; Cz: F(1,37) = 798.42, P < 0.05). CONCLUSION: A single-dose of chloral hydrate impacts neonatal auditory perception in the short-term. Long-term effects will also be studied in future.

Comparison of chloral hydrate and pentobarbital sedation for pediatric echocardiography.

BACKGROUND: In 2013, outpatient use of chloral hydrate (CH) was limited and other alternatives such as oral pentobarbital (PB) were explored to achieve conscious sedation in young children for transthoracic echocardiography (TTE). We aimed to assess efficacy and safety of the two medications. METHODS: Clinical information, from a computerized database, about children who received sedation with either CH or PB for TTE at our center (2008-2015) was reviewed, and the two groups were compared for sedation effectiveness and complications. RESULTS: Three thousand eight hundred fifty one pediatric patients (median age 8 months) underwent conscious sedation during TTE (mean doses CH 50 mg/kg, PB 4 mg/kg). Demographic characteristics of the two groups were similar. Sedation failure rate (CH 2.4%, PB 2.9%, P = NS), need for supplemental doses (CH 17.9%, PB 16.2%, P = NS), and overall adverse event rate (PB 1.4%, CH 1.9%; P = NS) were similar in the two groups. There were fewer episodes of respiratory depression with PB (0.3% vs 1.6%, P < 0.05). The rate of paradoxical reactions was higher with PB (1% vs 0.03%, P < 0.05). Increasing age predicted the need for supplemental doses and for sedation failure in both groups. Neonates (7.5% vs 0%) and infants (2% vs 0.6%) given CH were more likely to develop adverse reactions. CONCLUSION: Chloral hydrate and PB are equally effective. However, CH is associated with an increased incidence of transient desaturation, while PB is associated with an increased incidence of a paradoxical reaction. Increasing age is predictive of the need for supplemental doses and for failure of sedation in both groups.

Sedation of children undergoing dental treatment.

BACKGROUND: Children's fear about dental treatment may lead to behaviour management problems for the dentist, which can be a barrier to the successful dental treatment of children. Sedation can be used to relieve anxiety and manage behaviour in children undergoing dental treatment. There is a need to determine from published research which agents, dosages and regimens are effective. This is the second update of the Cochrane Review first published in 2005 and previously updated in 2012. OBJECTIVES: To evaluate the efficacy and relative efficacy of conscious sedation agents and dosages for behaviour management in paediatric dentistry. SEARCH METHODS: Cochrane Oral Health's Information Specialist searched the following databases: Cochrane Oral Health's Trials Register (to 22 February 2018); the Cochrane Central Register of Controlled Trials (CENTRAL; 2018, Issue 1) in the Cochrane Library (searched 22 February 2018); MEDLINE Ovid (1946 to 22 February 2018); and Embase Ovid (1980 to 22 February 2018). The US National Institutes of Health Ongoing Trials Register (ClinicalTrials.gov) and the World Health Organization International Clinical Trials Registry Platform were searched for ongoing trials. No restrictions were placed on the language or date of publication when searching the electronic databases. SELECTION CRITERIA: Studies were selected if they met the following criteria: randomised controlled trials of conscious sedation comparing two or more drugs/techniques/placebo undertaken by the dentist or one of the dental team in children up to 16 years of age. We excluded cross-over trials. DATA COLLECTION AND ANALYSIS: Two review authors independently extracted, in duplicate, information regarding methods, participants, interventions, outcome measures and results. Where information in trial reports was unclear or incomplete authors of trials were contacted. Trials were assessed for risk of bias. Cochrane statistical guidelines were followed. MAIN RESULTS: We included 50 studies with a total of 3704 participants. Forty studies (81%) were at high risk of bias, nine (18%) were at unclear risk of bias, with just one assessed as at low risk of bias. There were 34 different sedatives used with or without inhalational nitrous oxide. Dosages, mode of administration and time of administration varied widely. Studies were grouped into placebo-controlled, dosage and head-to-head comparisons. Meta-analysis of the available data for the primary outcome (behaviour) was possible for studies investigating oral midazolam versus placebo only. There is moderate-certainty evidence from six small clinically heterogeneous studies at high or unclear risk of bias, that the use of oral midazolam in doses between 0.25 mg/kg to 1 mg/kg is associated with more co-operative behaviour compared to placebo; standardized mean difference (SMD) favoured midazolam (SMD 1.96, 95% confidence interval (CI) 1.59 to 2.33, P < 0.0001, I2 = 90%; 6 studies; 202 participants). It was not possible to draw conclusions regarding the secondary outcomes due to inconsistent or inadequate reporting or both. AUTHORS' CONCLUSIONS: There is some moderate-certainty evidence that oral midazolam is an effective sedative agent for children undergoing dental treatment. There is a need for further well-designed and well-reported clinical trials to evaluate other potential sedation agents. Further recommendations for future research are described and it is suggested that future trials evaluate experimental regimens in comparison with oral midazolam or inhaled nitrous oxide.

A randomized controlled trial of oral chloral hydrate vs intranasal dexmedetomidine plus buccal midazolam for auditory brainstem response testing in children.

BACKGROUND: Moderate to deep sedation is required for an auditory brainstem response test when high-intensity stimulation is used. Chloral hydrate is the most commonly used sedative, whereas intranasal dexmedetomidine is increasingly used in pediatric non-painful procedural sedations. OBJECTIVE: The aim of this study was to compare the sedation success rate after oral chloral hydrate at 50 mg kg-1 and intranasal dexmedetomidine at 3 µg kg-1 plus buccal midazolam at 0.1 mg kg-1 for an auditory brainstem response test. METHODS: Children who required an auditory brainstem response test were recruited and randomly assigned to receive oral chloral hydrate at 50 mg kg-1 and intranasal placebo, or intranasal dexmedetomidine at 3 µg kg-1 with buccal midazolam 0.1 mg kg-1 . The primary outcome was the rate of successful sedation for auditory brainstem response tests. RESULTS: Fifty-seven out of 82 (69.5%) were successfully sedated after chloral hydrate, while 70 out of 78 (89.7%) children were successfully sedated with dexmedetomidine plus midazolam combination, with the odd ratio (95% CI) for successful sedation between dexmedetomidine plus midazolam combination and chloral hydrate estimated to be 3.84 (1.61-9.16), P = 0.002. Dexmedetomidine plus midazolam was associated with quicker onset with median onset time 15 (IQR 11.0-19.8) for dexmedetomidine plus midazolam and 20 (IQR 15.0-27.0) for chloral hydrate respectively, with difference between median (95% CI) of 5 [3-8], P < 0.0001). The behavior observed during drug administration of intranasal dexmedetomidine and buccal midazolam was better that of the children who had oral chloral hydrate. No children required oxygen therapy or medical intervention for hemodynamic disturbances in this study and the incidence of hypotension and bradycardia was similar. CONCLUSION: Intranasal dexmedetomidine plus buccal midazolam was associated with higher sedation success with deeper level of sedation, with similar discharge time and adverse event rate when compared to chloral hydrate.

Beta-adrenergic activation induces cardiac collapse by aggravating cardiomyocyte contractile dysfunction in bupivacaine intoxication.

In order to determine the role of the adrenergic system in bupivacaine-induced cardiotoxicity, a series of experiments were performed. In an animal experiment, male Sprague-Dawley (SD) rats under chloral hydrate anesthesia received intravenous bupivacaine, followed by an intravenous injection of adrenalin or isoprenalin, and the electrocardiogram (ECG), left ventricular systolic pressure (LVSP), left ventricular end-diastolic pressure (LVEDP), the maximum rate of rise of left ventricular pressure (+dP/dtmax) and the maximum rate of pressure decrease (-dP/dtmax) were continually monitored. In a cellular experiment, freshly isolated adult SD rat ventricular myocytes were perfused with bupivacaine at different concentrations in the presence or absence of isoprenalin, with or without esmolol. The percentage of the sarcomere shortening (bl% peak h), departure velocity (dep v) of sarcomere shortening and time to 50% of the peak speed of myocyte contraction (Tp50) was assessed by a video-based edge-detection system. In an additional experiment, Swiss mice pretreated with saline, isoprenalin, esmolol or dexmedetomidine received bupivacaine to determine the 50% lethal dose (LD50) of bupivacaine. Electron microscopy of myocardial mitochondria was performed to assess damage of these structures. To test mitochondrial reactive oxygen species (ROS) production, freshly isolated SD rat ventricular myocytes were incubated with bupivacaine in the presence of isoprenalin, with or without esmolol. First, our results showed that bupivacaine significantly reduced the LVSP and +dP/dtmax, as well as enhanced the LVEDP and -dP/dtmax (P < 0.05, vs. control, and vs. baseline). Adrenalin and isoprenalin induced a further reduction of LVSP and +dP/dtmax (P < 0.05, vs. before adrenalin or isoprenalin delivery, and vs. control). Second, bupivacaine induced a dose-dependent cardiomyocyte contractile depression. While 5.9 µmol/L or 8.9 µmol/L of bupivacaine resulted in no change, 30.0 µmol/L of bupivacaine prolonged the Tp50 and reduced the bl% peak h and dep v (P < 0.05, vs. control and vs. baseline). Isoprenalin aggravated the bupivacaine-induced cardiomyocyte contractile depression, significantly prolonging the Tp50 (P < 0.05, vs. bupivacaine alone) and reducing the dep v (P < 0.05, vs. bupivacaine alone). Third, esmolol and dexmedetomidine significantly enhanced, while isoprenalin significantly reduced, the LD50 of bupivacaine in mice. Fourth, bupivacaine led to significant mitochondrial swelling, and the extent of myocardial mitochondrial swelling in isoprenalin-pretreated mice was significantly higher than that compared with mice pretreated with saline, as reflected by the higher mitochondrial damage score (P < 0.01). Meanwhile, esmolol pretreatment significantly reduced the mitochondrial damage score (P < 0.01). Fifth, bupivacaine significantly increased the ROS in freshly isolated cardiomyocytes, and added isoprenalin induced a further enhancement of ROS production (P < 0.05, vs. bupivacaine alone). Added esmolol significantly decreased ROS production (P < 0.05, vs. bupivacaine + isoprenalin). Our results suggest that bupivacaine depressed cardiac automaticity, conductivity and contractility, but the predominant effect was contractile dysfunction which resulted from the disruption of mitochondrial energy metabolism. ß-adrenergic activation aggravated the cellular metabolism disorder and therefore contractile dysfunction.

Cervical Vestibular-Evoked Myogenic Potentials in Sedated Toddlers

Abstract Introduction Cervical vestibular-evoked myogenic potentials (cVEMPs) are difficult to test in toddlers who cannot follow instructions or stay calm. Objective Due to the growing need for vestibular testing in very young children as a part of a delayed walking assessment battery, this study aimed to provide a solution to this problem by recording the cVEMPs in toddlers during sedation. Method The cVEMPs measures were assessed in 30 toddlers aged 12 to 36 months with normal motormilestones. They were sedated with chloral hydrate. Then, the head was retracted ~ 30° backward with a pillow under the shoulders, and turned 45° contralateral to the side of stimulation to put the sternocleidomastoid (SCM)muscle in a state of tension. Results The P13 and N23 waves of the cVEMPs were recordable in all sedated toddlers. The cVEMPs measures resulted in the following: P13 latency of 17.5 ± 1.41 milliseconds, N23 latency of 25.58 ± 2.02 milliseconds, and peak-topeak amplitude of 15.39 ± 3.45 μV. One-sample t-test revealed statistically significant longer latencies and smaller amplitude of the toddlers' cVEMPs relative to the normative data for adults. Conclusions The difficulty of cVEMPs testing in toddlers can be overcome by sedating them and attaining a position that contracts the SCM muscle. However, the toddlers' recordings revealed delayed latencies and smaller amplitudes than those of adults.