Efficacy and safety of chloral hydrate in auditory brainstem response test: A systematic review and single-arm meta-analysis.

OBJECTIVES: To evaluate the safety and efficacy of chloral hydrate in auditory brainstem response (ABR) tests. SETTING AND DESIGN: In this study, the authors systematically searched both English (Embase, PubMed, and Web of Science) and Chinese (Chinese National Knowledge Infrastructure, Wanfang Data, and VIP Chinese Science) databases. Two authors independently performed data extraction and quality assessment. The pooled sedation failure rate and the pooled incidence of adverse events were calculated via a random-effects model. Sensitivity and subgroup analyses were performed to explore the sources of heterogeneity, and the PRISMA guideline was followed. PARTICIPANTS: Patients with ABR tests receiving chloral hydrate sedation. MAIN OUTCOME MEASURES: The pooled sedation failure rate and the pooled incidence of adverse events. RESULTS: A total of 23 clinical studies were included in the final analysis. The pooled sedation failure rate of patients who received chloral hydrate sedation before ABR examination was 10.0% [95% confidence interval (CI) (6.7%, 15.0%), I2 = 95%, p < .01]. There were significant differences in the prevalence of sedation failure between sample sizes greater than 200 and those less than or equal to 200 (5.6% vs. 19.6%, p < .01) and between the studies that reported sleep deprivation and those that did not report sleep deprivation (7.1% vs. 18.9%, p < .01). The pooled incidence of adverse events was 10.32% [95% CI (5.83%, 14.82%), I2 = 98.1%, p < .01]. CONCLUSIONS: Chloral hydrate has a high rate of sedation failure, adverse events, and potential carcinogenicity. Therefore, replacing its use in ABR tests with safer and more effective sedatives is warranted.

Dynamic effects of miR-20a-5p on hippocampal ripple energy after status epilepticus in rats.

To determine the dynamic effects of miR-20a-5p on hippocampal ripple energy in rats after status epilepticus (SE). A lithium pilocarpine (LiCl-PILO)-induced rat model of status epilepticus (SE) was established, and the rats were divided into the normal control (Control, CTL), epileptic control (PILO), valproic acid (VPA + PILO), miR-20a-5p overexpression lentivirus vector (miR + PILO), sponges blocking lentivirus vector (Sponges + PILO), and scramble sequence negative control (Scramble + PILO) groups (n = 6). Electroencephalograms (EEGs) were used to analyze changes in hippocampal ripple energy before and after SE. Quantitative polymerase chain reaction (q-PCR) analysis showed that miR-20a-5p levels gradually increased after miR-20a-5p overexpression lentivirus vector injection into the lateral ventricle, and the miR-20a-5p levels were significantly higher than that in CTL group on days 7 and 36 (P < 0.001). The miR-20a-5p levels decreased significantly on days 7 and 36 after blocking by sponges lentivirus vector injected into the lateral ventricle (P < 0.001). After injection of PILO, the average ripple energy expression in each group gradually increased, and reached the peak before chloral hydrate injection (compared with 1 day before SE, P < 0.05). The ripple energy in the VPA + PILO and Sponges + PILO groups was significantly lower than that in the PILO group at 60 min and 70 min after PILO injection and before chloral hydrate injection (P < 0.05), and maintained lower until 2 h after chloral hydrate injection in VPA + PILO (P < 0.05). Compared with the VPA + PILO group, the mean ripple energy of the Sponges + PILO group had no difference at all time points (P ≥ 0.05). After SE, ripple distribution of space and energy is closely related to the occurrence of epilepsy. Inhibition of miR20a-5p expression can downregulate ripple oscillation energy during seizure.

Safety and efficacy of pediatric sedation protocol for diagnostic examination in a pediatric emergency room: A retrospective study.

Pediatric patients undergoing diagnostic tests in the pediatric emergency room are frequently sedated. Although efforts are made to prevent adverse events, no sedation protocol has specified the optimal regimen, dosage, and interval of medication to prevent adverse events. This study analyzed the safety and efficacy of sequential pediatric sedation protocols for pediatric patients undergoing diagnostic tests in the pediatric emergency room of a single tertiary medical center. The medical records of patients aged < 18 years who visited the pediatric emergency room of Seoul Asan Medical Center between January and December 2019 for diagnostic testing were retrospectively reviewed. Sedation protocols consisted of 50 mg/kg and 25 mg/kg chloral hydrate, 0.1 mg/kg and 0.1 mg/kg midazolam, and 1 mg/kg and 0.5 to 1 mg/kg ketamine, administered sequentially at intervals of 30, 20, 10, 10, and 10 minutes, respectively. Patients were assessed prior to sedation, and adverse events were investigated. Of the 289 included patients, 20 (6.9%) experienced adverse events, none serious, and nine (3.1%) failed to reach the depth of sedation required to complete the test. The regimen (P = .622) and dosage (P = .777) of the sedatives were unrelated to the occurrence of adverse events when sedation was performed according to protocol. The sedation protocol used in these patients, consisting of sequential administration of minimum dosages, achieved a sufficient depth of sedation with relatively few adverse events, indicating that this protocol can be used safely and effectively for painless sedation in pediatric patients undergoing diagnostic testing.

French survey of sedation practices for pediatric magnetic resonance and computed tomography imaging.

BACKGROUND: Pediatric magnetic resonance imaging (MRI) and computed tompgraphy (CT) require patient immobility and therefore often require sedation or general anesthesia of patients. Consensus on these procedures is lacking in France. OBJECTIVE: Thus, the aim of this study was to describe the current sedation practices for pediatric MRI and CT in France. MATERIAL AND METHODS: From January 2019 to December 2019, an online questionnaire was delivered by electronic mail to a representative radiologist in 60 pediatric radiology centers registered by the French-speaking pediatric and prenatal imaging society. Questions included protocols, drugs used, monitoring and side effects. RESULTS: Representatives of 40 of the 60 (67%) radiology centers responded to the survey. Among them, 31 performed sedation including 17 (55%) centers where radiologists performed sedation without anesthesiologists present during the procedure. The premedication drugs were hydroxyzine (n = 8, 80%) and melatonin (n = 2, 20%), Sedation drugs used for children ages 0 to 6 years old were pentobarbital (n = 9, 60%), midazolam (n = 2, 13%), chloral hydrate (n = 2, 13%), diazepam (n = 1, 6.5%) and chlorpromazine (n = 1, 6.5%). A written sedation protocol was available in 10/17 (59%) centers. In 6/17 (35%) centers, no monitoring was used during the procedures. Blood pressure monitoring and capnography were rarely used (< 10%) and post-sedation monitoring was heterogeneous. No life-threatening adverse effect was reported, but 6 centers reported at least one incident per year. CONCLUSION: For half of the responding radiology centers, radiologists performed sedation alone in agreement with the local anesthesiology team. Sedation procedures and monitoring were heterogenous among centers. Adjustment and harmonization of the practices according to the capacity of each center may be useful.

Needle-free pharmacological sedation techniques in paediatric patients for imaging procedures: a systematic review and meta-analysis.

BACKGROUND: Sedation techniques and drugs are increasingly used in children undergoing imaging procedures. In this systematic review and meta-analysis, we present an overview of literature concerning sedation of children aged 0-8 yr for magnetic resonance imaging (MRI) procedures using needle-free pharmacological techniques. METHODS: Embase, MEDLINE, Web of Science, and Cochrane databases were systematically searched for studies on the use of needle-free pharmacological sedation techniques for MRI procedures in children aged 0-8 yr. Studies using i.v. or i.m. medication or advanced airway devices were excluded. We performed a meta-analysis on sedation success rate. Secondary outcomes were onset time, duration, recovery, and adverse events. RESULTS: Sixty-seven studies were included, with 22 380 participants. The pooled success rate for oral chloral hydrate was 94% (95% confidence interval [CI]: 0.91-0.96); for oral chloral hydrate and intranasal dexmedetomidine 95% (95% CI: 0.92-0.97); for rectal, oral, or intranasal midazolam 36% (95% CI: 0.14-0.65); for oral pentobarbital 99% (95% CI: 0.90-1.00); for rectal thiopental 92% (95% CI: 0.85-0.96); for oral melatonin 75% (95% CI: 0.54-0.89); for intranasal dexmedetomidine 62% (95% CI: 0.38-0.82); for intranasal dexmedetomidine and midazolam 94% (95% CI: 0.78-0.99); and for inhaled sevoflurane 98% (95% CI: 0.97-0.99). CONCLUSIONS: We found a large variation in medication, dosage, and route of administration for needle-free sedation. Success rates for sedation techniques varied between 36% and 98%.

Comparison of cerebral oxygen desaturation events between children under general anesthesia and chloral hydrate sedation - a randomized controlled trial.

BACKGROUND: During pediatric general anesthesia (GA) and sedation, clinicians aim to maintain physiological parameters within normal ranges. Accordingly, regional cerebral oxygen saturation (rScO2) should not drop below preintervention baselines. Our study compared rScO2 desaturation events in children undergoing GA or chloral hydrate sedation (CHS). METHODS: Ninety-two children undergoing long auditory assessments were randomly assigned to two study arms: CHS (n = 40) and GA (n = 52). Data of 81 children (mean age 13.8 months, range 1-36 months) were analyzed. In the GA group, we followed a predefined 10 N concept (no fear, no pain, normovolemia, normotension, normocardia, normoxemia, normocapnia, normonatremia, normoglycemia, and normothermia). In this group, ENT surgeons performed minor interventions in 29 patients based on intraprocedural microscopic ear examinations. In the CHS group, recommendations for monitoring and treatment of children undergoing moderate sedation were met. Furthermore, children received a double-barreled nasal oxygen cannula to measure end-tidal carbon dioxide (etCO2) and allow oxygen administration. Chloral hydrate was administered in the parent's presence. Children had no intravenous access which is an advantage of sedation techniques. In both groups, recommendations for fasting were followed and an experienced anesthesiologist was present during the entire procedure. Adverse event (AE) was a decline in cerebral oxygenation to below 50% or below 20% from the baseline for ≥1 min. The primary endpoint was the number of children with AE across the study arms. Secondary variables were: fraction of inspired oxygen (FIO2), oxygen saturation (SpO2), etCO2, systolic and mean blood pressure (BP), and heart rate (HR); these variables were analyzed for their association with drop in rScO2 to below baseline (%drop_rScO2). RESULTS: The incidence of AE across groups was not different. The analysis of secondary endpoints showed evidence that %drop_rScO2 is more dependent on HR and FIO2 than on BP and etCO2. CONCLUSIONS: This study highlights the strong association between HR and rScO2 in children aged < 3 years, whereas previous studies had primarily discussed the role of BP and etCO2. Prompt HR correction may result in shorter periods of cerebral desaturation. TRIAL REGISTRATION: The study was retrospectively registered with the German Clinical Trials Registry (DRKS00024362, 04/02/2021).

Comparisons of Varying Dosages of Chloral Hydrate-Hydroxyzine with and without Meperidine for Managing Challenging Pediatric Dental Behavior: A Retrospective study of 35 years of Sedation Experiences.

PURPOSE: This retrospective study compares the efficacy and safety of variable dosing of Chloral Hydrate - Hydroxyzine with and without Meperidine (Mep)for managing varying levels of anxiety and uncooperative behavior of young pediatric dental patients over a 35-year period. STUDY DESIGN: Reviews of the sedation logs of 2,610 children, 3-7 years were compared in search of what dosing proves safe and effective for differing levels of challenging behavior. Variable dosing of CH with and without Mep were judged using a pragmatic approach which defined sedation success as optimal, adequate, inadequate, or over-dosage using oneway analysis of variance. Descriptive analyses of behavior and physiologic assessment was included with regard to the extent to which physical restraint occurred to control interfering behavior. Arousal levels requiring stimulation, oxygen desaturation, and adverse reactions were included as indications of safety. RESULTS: Where Mep was used, success rates were consistently higher; need for higher-end dosing of CH was not found beneficial when Mep was included. Significantly less need for physical restraint accompanied the addition of Mep. CONCLUSIONS: There appears to be strong basis for the safety and efficacy of the use of CH-H-Mep in combination at lower dosing than historically used. Addition of Mep was observed to enhance sedations, permit lower CH dosing, lessen or eliminate the need for physical restraint and adverse reactions.

Use of a single dose of 70mg/kg chloral hydrate as a hypnotic in nuclear magnetic resonance. A prospective study of 3132 cases.

OBJECTIVE: To assess the mean time to hypnosis, hemodynamic stability, and incidence of complications associated with the administration of 70mg/kg oral chloral hydrate in children scheduled for magnetic resonance imaging (MRI). MATERIAL AND METHODS: Prospective study conducted from January 2000 to January 2020 in which 3132 patients aged between one day and 5 years underwent MRI under anaesthesia in an outpatient setting. The study population was divided into 4 subgroups: A) aged between one and 30 days; B) aged between one month and one year; C) aged between one and 3 years, and D) aged between 3 and 5 years. Study variables were: sex, age, type of examination, mean imaging time, mean time to awakening, heart rate before and after MRI, SatO2, and incidence of complications such as respiratory depression (SatO2 below 90%), agitation during the MRI or on awakening (intense crying lasting more than 2min), prolonged sedation measured on the Steward scale, and nausea and/or vomiting during the MRI, on awakening, or at home. RESULTS: No notable hemodynamic alterations were observed. The incidence of desaturation was .41%, awakening during the test was .16%, prolonged sedation was 1.08%, and agitated awakening was 1.46%. Nausea and vomiting at the end of the test had an incidence of .73%. The P value in all cases was <.05%. CONCLUSIONS: Chloral hydrate at a dose of 70mg/kg continues to be suitable in sedation lasting no more than one hour for non-invasive procedures in children, and is associated with adequate haemodynamic stability with practically no side effects.

Analysis of Risk Factors for Chloral Hydrate Sedative Failure with Initial Dose in Pediatric Patients: a Retrospective Analysis.

BACKGROUND: Although chloral hydrate has been used as a sedative for more than 100 years, dozens of studies have reported that it has inconsistent sedative effects and high sedation failure rates with initial dose. The high failure rates may lead to repeated administration of sedatives, guardians' dissatisfaction, parental anxiety, increasing medical workload as well as leading to an increase of adverse events. Our aim is to identify the risk factors associated with chloral hydrate sedative failure with initial dose in children undergoing noninvasive diagnostic procedures. METHODS: Pediatric patients who underwent chloral hydrate sedation for noninvasive diagnostic procedures at our institution between 1 December 2019 and 1 January 2021 were retrospectively analyzed. Data collected included patients' age, gender, weight, sedation history, sedation failure history, type of procedures, initial dose of choral hydrate, sleep deprivation, sedation failure with initial dose, and sedative duration. The initial dose was classified into three levels: reduced dose (< 40 mg/kg), standard dose (40-60 mg/kg), and high dose (> 60 mg/kg). The patients were divided into three cohorts according to the different initial doses. RESULTS: A total of 15,922 patients were included in the analysis; 1928 (12.1%) were not well-sedated after administering the initial dose of chloral hydrate. The highest sedative failure was observed in the reduced dose group. By multivariate regression, we identified that heavier weight, patients with a history of sedation or a history of sedation failure, and patients who received magnetic resonance imaging (MRI) or more than one procedure simultaneously were associated with an increased odds of sedation failure at the initial dose. However, outpatients, patients undergoing hearing screening, and patients with sleep deprivation were favored regarding chloral hydrate sedative success. CONCLUSION: An alternative drug or drug combination is necessary in patients with heavier weight, those with a sedation history or sedation failure history, and those undergoing an MRI or more than one procedure simultaneously, whereas chloral hydrate is an appropriate sedation option for outpatients, patients undergoing hearing screening, and those with sleep deprivation.

Dexmedetomidine improves success of paediatric MRI sedation.

OBJECTIVE: To improve success rates of children requiring sedation for MRI. METHODS: Audits of sedation success for children attending planned MRI using three different approaches: (1) National Institute for Health and Care Excellence (NICE) guidance (chloral hydrate if <15 kg and oral midazolam if ≥15 kg), (2) Chloral hydrate for all patients, (3) Chloral hydrate±intranasal dexmedetomidine if <15 kg and intranasal dexmedetomidine alone if ≥15 kg. RESULTS: 74 patients had 85 MRI scan attempts. Overall success rates were significantly higher when using intranasal dexmedetomidine compared with following NICE guidance (81% vs 52% p=0.017). Dexmedetomidine performed better than oral midazolam for the same indication (76% vs 33% p=0.026). The side effect profile for dexmedetomidine was as reported in larger studies. CONCLUSIONS: Intranasal dexmedetomidine is an effective alternative to oral midazolam for sedation for MRI and as a rescue medication where chloral hydrate has been ineffective.

Efficacy and safety of intranasal dexmedetomidine versus oral chloral hydrate as sedatives for pediatric patients: a systematic review and meta-analysis.

This study was designed to review published literature to determine the efficacy and safety of intranasal dexmedetomidine versus oral chloral hydrate (CH) for sedation in pediatric patients based on qualified studies. We searched the PubMed, Cochrane, and Embase databases for qualified studies published before March 2021. For each study, we analyzed the relative risk or weighted mean difference combined with a 95% CI. Fourteen studies including 3749 pediatric patients were included in this meta-analysis. Compared with oral CH, intranasal dexmedetomidine significantly increased the success rate of sedation and decreased the duration and latency of sedation, time of recovery from sedation, and total sedation time. Compared with oral CH, intranasal dexmedetomidine significantly decreased the incidence of adverse events, including vomiting, but increased the incidence of bradycardia. In conclusion, intranasal dexmedetomidine provides better sedation than oral CH for pediatric patients with good safety; however, the incidence of bradycardia is increased.

Trends and patterns in the practice of pediatric sedation for magnetic resonance imaging in Japan: A longitudinal descriptive study from 2012 to 2019.

BACKGROUND: Worldwide, pediatric sedation for magnetic resonance imaging is a standard practice; however, there are few studies on its trends and patterns. AIMS: This study aimed to investigate the trends and patterns of pediatric sedation for magnetic resonance imaging in Japan and determine the incidence of and risk factors for adverse events/interventions. METHODS: This longitudinal descriptive study assessed children (age < 15 years) who underwent sedation for magnetic resonance imaging between April 2012 and December 2019 in Japan using a nationwide claims database. We assessed the patients' demographic characteristics, time trends in sedatives, sedative patterns by age, and adverse events/interventions within two post-sedation days. Further, we used multivariable logistic regression models to explore factors related to the incidence of adverse events/interventions. RESULTS: We identified 29 187 cases (median age, 2.0 years; 55.2% males). The most common sedative was triclofos sodium (n = 18 812, 51.7%). There was an increasing trend in barbiturate use (17.0% [2012] to 25.0% [2019]) and decreasing trends in the use of triclofos sodium (56.4% [2012] to 47.7% [2019]) and chloral hydrate (15.6% [2012] to 10.8% [2019]). We identified 534 adverse events/interventions in 460 cases (1.5%). Multivariable logistic regression analyses revealed that the incidence of adverse events/interventions mainly increased with the number of sedatives (≥3; adjusted odds ratio, 5.10; 95% confidence interval, 3.67-7.10) and unscheduled setting (adjusted odds ratio, 6.28; 95% confidence interval, 4.85-8.61); further, it decreased with high hospital procedure volume (adjusted odds ratio, 0.62; 95% confidence interval, 0.49-0.78). CONCLUSIONS: Based on a Japanese real-world setting, there is an increasing trend in barbiturate use and decreasing trends in the use of triclofos sodium and chloral hydrate in pediatric sedation for magnetic resonance imaging. Low hospital procedure volumes were associated with an increased risk of adverse events/interventions.

The safety and efficacy of a nurse-led sedation service using Chloral Hydrate for auditory brainstem response testing.

BACKGROUND: There is a growing number of pediatric procedures requiring sedation outside the operating room. Among these are auditory brainstem response (ABR) tests, the gold standard for objective hearing evaluation in infants and toddlers. Recently, a nurse-led pediatric sedation service based on a structured protocol has been developed for ABR testing. OBJECTIVES: To retrospectively analyze the safety and efficacy of the pediatric nurse-led sedation protocol (PNLSP) in a tertiary medical center using Chloral Hydrate (CH) in children undergoing ABR testing. METHODS: Data from medical charts of children who underwent sedation for ABR testing between January 2014 and December 2017, were retrieved. Analysis of sedation success/failure rates, sleep induction time (SIT), sleep duration time (SDT), and adverse events (AE), was performed. FINDINGS: 1348 children with a mean age of 13.4 months (range 3-42 months), classified by the American Society of Anesthesiologists Physical Status Classification System (ASA score) 1-3, were included in the analysis. All children received a fixed dose of 75 mg / kg CH orally or rectally. Sedation success rate was 98.7% and enabled completion of ABR testing. Failure to sedate was evident in 17 children (1.3%), all classified as ASA score 1-2. Median SIT and SDT were 25 and 100 min, respectively. Mild AE occurred in 9 children (0.67%), none of which required further intervention. CONCLUSIONS: Findings support the use of a structured PNLSP using CH as safe and efficient. The suggested protocol is an effective alternative for general anesthesia (GA) for ABR testing in healthy young children.

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.

Sleep deprivation did not enhance the success rate of chloral hydrate sedation for non-invasive procedural sedation in pediatric patients.

STUDY OBJECTIVE: In Asian countries, oral chloral hydrate is the most commonly used sedative for non-invasive procedures. Theoretically, mild sleep deprivation could be considered as one of assisted techniques. However, there is no consensus on sleep deprivation facilitating the sedation during non-painful procedures in children. The aim of our study is to analyze the clinical data of children undergoing non-invasive procedural sedation retrospectively and to evaluate the association between mild sleep deprivation and sedative effects in non-invasive procedures. MEASUREMENTS: Consecutive patients undergoing chloral hydrate sedation for non-invasive procedures between December 1, 2019 to June 30, 2020 were included in this study. The propensity score analysis with 1: 1 ratio was used to match the baseline variables between patients with sleep deprivation and non-sleep deprivation. The primary outcome was the failure rate of sedation with the initial dose. The secondary outcomes included the failure rate of sedation after supplementation of chloral hydrate, the incidence of major and minor adverse events, initial and supplemental dose of chloral hydrate, and the length of sedation time. MAIN RESULTS: Of the 7789 patients undergoing chloral hydrate sedation, 6352 were treated with sleep deprivation and 1437 with non-sleep deprivation. After propensity score matching, 1437 pairs were produced. The failure rate of sedation with initial chlorate hydrate was not significantly different in two groups (8.6% [123/1437] vs. 10.6% [152/1437], p = 0.08), nor were the failure rates with supplemental chlorate hydrate (0.8% [12/1437] vs. 0.9% [13/1437], p = 1) and the length of sedation time (58 [45, 75] vs. 58 [45, 75] min; p = 0.93). CONCLUSIONS: The current results do not support sleep deprivation have a beneficial effect in reducing the pediatric chloral hydrate sedation failure rate. The routine use of sleep deprivation for pediatric sedation is unnecessary.

Cardiorespiratory parameters in newborns during sedation with chloral hydrate.

We commonly use chloral hydrate sedation in newborns, though its cardiorespiratory side effects have not yet been fully investigated. Our study aimed to analyze the impact of chloral hydrate on cardiorespiratory parameters in term newborns. We performed a prospective, pre-post single-arm interventional study in 42 term, respiratorily and hemodynamically stable newborns. Oxygen saturation (SpO2), end-tidal CO2 (ETCO2), the apnea-hypopnea index and the respiratory and heart rates were recorded by polygraphy, starting 0.5-1 hour before oral administration of chloral hydrate at a dose of 40 mg/kg and ceasing 4 hours post-administration. After administration of chloral hydrate, the mean basal SpO2 dropped by 2.0% (from 97.1% to 95.1%; p < 0.001) and the mean basal ETCO2 increased by 3.9 mmHg (25.6 to 29.5 mmHg; p < 0.001). We found a significant decrease in the minimal SpO2 values (p < 0.001) and an increase in the percentage of time spent with SpO2 < 95% and < 90% (p < 0.001). The mean increase in the estimated apnea-hypopnea index was 3.5 events per hour (p < 0.001). The mean respiratory and heart rates were significantly lower 150 min after the administration of chloral hydrate when compared with pre-sedation values (51/min and 127/min versus 61/min and 138/min respectively; p < 0.001). A considerable number of patients exhibited changes in cardiorespiratory parameters that differed considerably from the normal ranges. In conclusion, SpO2, ETCO2, the estimated apnea-hypopnea index and the respiratory and heart rates changed after the administration of chloral hydrate. They remained within normal limits in most newborns, but the inter-individual variability was high in the studied population.

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.

Dexmedetomidine versus other sedatives for non-painful pediatric examinations: A systematic review and meta-analysis of randomized controlled trials.

STUDY OBJECTIVE: Procedural sedation for non-painful pediatric examinations outside the operating room remains a challenge, this study was designed to compare the safety and effectiveness of sedation provided by dexmedetomidine versus other sedatives including chloral hydrate, midazolam, and pentobarbital for pediatric patients to complete diagnostic examinations. DESIGN: Systematic review and meta-analysis of RCTs. SETTING: Pediatric procedural sedation. INTERVENTIONS: Comparison of sedation by dexmedetomidine and chloral hydrate, or pentobarbital, or midazolam for pediatric non-painful sedation. PATIENTS: The PubMed, Embase, and Cochrane Library databases and the Cochrane Controlled Trials Register for randomized clinical trials were searched and limited the studies to those published in English through July 30, 2018. MEASUREMENTS: Prospective randomized clinical trials (RCTs) comparing dexmedetomidine to chloral hydrate, pentobarbital, and midazolam for pediatric procedural examinations outside the operating room were included in the meta-analysis. Search terms included dexmedetomidine, precede, adrenergic alpha-2 receptor agonists, adrenergic alpha 2 agonists, adrenergic alpha-agonists, adrenergic alpha 2 receptor agonists, chloral hydrate, pentobarbital, midazolam, AND sedation. MAIN RESULTS: A total of 1486 studies were screened and nine RCTs were identified; 1076 patients were analyzed. Sedation with dexmedetomidine provided statistically higher incidences in completing examinations with fewer episodes of desaturation than the other sedatives did (OR 2.90, 95% CI: 1.39-6.07, P = 0.005, I2 = 77%; OR 0.29, 95% CI: 0.15-0.57, P = 0.0004, I2 = 0%, respectively). CONCLUSIONS: The meta-analysis shows that sedation by dexmedetomidine has lower incidence of respiratory depression and provides higher success rates in completing examinations than other traditional sedatives without compromising safety, indicating a prospective clinical use for procedural sedation.

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.