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Background: This study aimed to investigate the risk factors for chloral hydrate sedation failure and complications in a tertiary children's hospital in South Korea. Methods: A retrospective analysis of pediatric procedural sedation with chloral hydrate between January 1, 2021, and March 30, 2022, was performed. The collected data included patient characteristics, sedation history, and procedure. Multivariable regression analysis was performed to identify the risk factors for procedural sedation failure and complications. Results: A total of 6,691 procedural sedation were included in the analysis; sedation failure following chloral hydrate (50 mg/kg) occurred in 1,457 patients (21.8%) and was associated with a higher rate of overall complications compared to those with successful sedation (17.5% [225/1457] vs. 6.2% [322/5234]; P < 0.001, odds ratio: 3.236). In the multivariable regression analysis, the following factors were associated with increased risk of sedation failure: general ward or intensive care unit inpatient (compared with outpatient); congenital syndrome; oxygen dependency; history of sedation failure or complications with chloral hydrate; procedure more than 60 min; and magnetic resonance imaging, radiotherapy, or procedures with painful or intense stimuli (all P values < 0.05). Factors contributing to the complications included general ward inpatient, congenital syndromes, congenital heart disease, preterm birth, oxygen dependency, history of complications with chloral hydrate, and current sedation failure with chloral hydrate (all P values < 0.05). Conclusions: To achieve successful sedation with chloral hydrate, the patient's sedation history, risk factors, and the type and duration of the procedure should be considered. [ABSTRACT FROM AUTHOR]

Objectives: Newborns and small infants are unable to cooperate actively during diagnostic procedures; therefore, sedation is often employee to maintain immobilization and obtain high-quality images. However, these procedures are often indicated in sick, vulnerable, or hemodynamically unstable neonates and young infants, which raises the associated risks of sedation. This study summarizes our 4-year of experience with safe and effective procedural sedation in this vulnerable population. Study design: This retrospective study analyzed data on neonates and young infants who underwent non-painful diagnostic procedures from December 2019 to November 2023. Patients were categorized into the neonate (aged ≦ 28 days) and the young infant (29 days ≦ aged ≦ 90 days) groups. Results: Non-pharmacological strategies, including sleeping naturally, swaddling/facilitated tucking, non-nutritive sucking, and skin-to-skin care, can achieve a success rate for sedation about 98.4%. In terms of pharmacological methods, our institution primarily utilizes chloral hydrate for procedural sedation in neonates and young infants undergoing non-painful diagnostic procedures. Midazolam serves as an alternative sedative. Chloral hydrate alone demonstrated a 92.5% success rate on the first attempt, compared to midazolam alone, with an 85.11% success rate. Neonates experienced a higher incidence of adverse events during sedation compared to young infants. Conclusion: This study reviews our 4-year experience with procedural sedation in neonates and young infants. Chloral hydrate demonstrated a high degree of safety and efficacy in this population. However, supervision by skilled medical personnel and extended observation is required. In our institution, the experience with midazolam is limited in this population, and further research is warranted to establish its safety and efficacy. Non-pharmacological strategies can achieve an acceptable rate of sedation success, which can be used based on patient's tolerance. [ABSTRACT FROM AUTHOR]

The aim of the study was to compare the effect of sevoflurane and chloral hydrate on the neurological status and volume of brain damage after trauma and ischemia in experimental models of traumatic brain injury (TBI) and focal ischemic stroke (IS) induced by photothrombosis (PT).Materials and methods. The experiments were performed on mongrel Wistar rats weighing 250–300 g (N=43). There were 4 groups: the Ischemia + Sevoflurane group (ISSEV) (N=10), the Ischemia + Chloral hydrate group (ISCH) (N=10), TBI + Sevoflurane group (TBISEV) (N=13), and TBI+Chloral hydrate group (TBICH) (N=10). Ischemic brain damage was modelled using Rose Bengal (RB) dye-induced PT, and TBI was modelled using mechanical force-induced concussion.Results. MRI findings indicate lower volumes of brain damage (mm³) in rats from TBISEV group compared with the TBICH group (19±5 vs. 60±5, P

Introduction: Chloral hydrate (CH), a medication dating back to 1832, is tranquilizer and sleep promoter still used today. It remains an option for short-term insomnia therapy and sedation before medical procedures, despite its controversial safety profile. Methods: This study investigated the potential benefits of chloral hydrate addition for increasing sleep duration and reducing agitation and violence in inpatients with treatment-resistant schizophrenia (TRS). A retrospective, observational case series design was utilized, analyzing data from fourteen patients diagnosed with TRS disorders. Results: CH addition increased the rate of full night sleep and decreased the rates of agitation and verbal and physical violence events. Notably, no adverse events including falls were reported during CH addition. Discussion: CH shows some short-term benefits in improving sleep disorders and reducing violent and agitated behavior in patients with TRS. Our study has limitations due to its small sample size, retrospective design and lack of a control group. A large-scale, double-blind, randomized trial is needed to further explore the efficacy and safety of CH in psychiatric populations with TRS accompanied by agitation, violence and disturbed sleep. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

IntroductionChloral hydrate (CH), a medication dating back to 1832, is tranquilizer and sleep promoter still used today. It remains an option for short-term insomnia therapy and sedation before medical procedures, despite its controversial safety profile.MethodsThis study investigated the potential benefits of chloral hydrate addition for increasing sleep duration and reducing agitation and violence in inpatients with treatment-resistant schizophrenia (TRS). A retrospective, observational case series design was utilized, analyzing data from fourteen patients diagnosed with TRS disorders.ResultsCH addition increased the rate of full night sleep and decreased the rates of agitation and verbal and physical violence events. Notably, no adverse events including falls were reported during CH addition.DiscussionCH shows some short-term benefits in improving sleep disorders and reducing violent and agitated behavior in patients with TRS. Our study has limitations due to its small sample size, retrospective design and lack of a control group. A large-scale, double-blind, randomized trial is needed to further explore the efficacy and safety of CH in psychiatric populations with TRS accompanied by agitation, violence and disturbed sleep.

Sedation plays a crucial role in successful pediatric imaging, and chloral hydrate is commonly used for this purpose. However, the challenges associated with chloral hydrate administration, such as its unpleasant taste and potential induction of vomiting, remain a concern. Sweet oral solutions have emerged as potential solutions for reducing distress and providing analgesia. This study compared the efficacy of dextrose combined with chloral hydrate with that of conventional sedation methods. This prospective, double-blind, randomized controlled clinical study enrolled 160 pediatric outpatients scheduled for echocardiography. Chloral hydrate syrup (100 mg/mL) was supplemented with a dextrose solution (dextrose group) or distilled water (control group) in a 1:10 volume ratio. The sedation achievement time, Skeie scale score, revised Face, Legs, Activity, Cry, and Consolability (FLACC) score, and side effects (nausea, vomiting, hypoxia, and respiratory depression) were assessed. No significant difference in average time to achieve sedation was observed between the dextrose and control groups (24.4±17.8 vs. 24.7±17.1 min, p=0.92). Both groups demonstrated similar levels of sedation according to the Skeie scale and mean revised FLACC score. Although the occurrence rates of nausea and vomiting had no significant differences, the dextrose group had no cases of vomiting in children aged >24 months compared to the control group, which had three cases (30%). In conclusion, the addition of dextrose to chloral hydrate did not significantly affect sedation time, anxiety, pain reduction, or occurrence of gastrointestinal complications during sedation. [ABSTRACT FROM AUTHOR]

The administration of oral sedatives for minimal and moderate sedation is common practice for pediatric dentistry. Being up to date with contemporary medications and dosing recommendations is imperative for patient safety. Historic medications such as chloral hydrate have become obsolete with the introduction of benzodiazepines and other newer medications such as alpha-2 adrenergic agonists. Oral opioids are useful for analgesia and mild sedation but may result in significant respiratory depression when combined with other central nervous system depressants and, if left untreated, hypoxemia. Antihistamines can provide minimal sedation but may have other added benefits such as antiemetic and antisialagogue effects. This review will discuss relevant pharmacologic aspects, including onset, duration of action, metabolism, and adverse reactions, for several common agents used for minimal and moderate oral sedation to assist practitioners in determining ideal medications or combinations that fit the needs of the pediatric patient and dental procedure contingent upon the provider's level of training. [ABSTRACT FROM AUTHOR]

Objective To compare the efficacy of melatonin, melatonin with sleep deprivation, and chloral hydrate with sleep deprivation on sleep induction in Asian children. Methods: For this randomized single-blind controlled trial, we recruited 45 children aged 1–5 years and older who were not cooperative on electroencephalogram (EEG) recordings, randomly allocated to three groups: melatonin (group A), melatonin and sleep deprivation (group B), or chloral hydrate and sleep deprivation (group C). Between-group comparisons were performed using the Kruskal–Wallis and Mann–Whitney U tests. Results: Stage II sleep was achieved in 92.8%, 100%, and 100% of participants in groups A, B, and C, respectively. Sleep latency was significantly shorter in Group C than in Groups A (p =.022) and B (p =.027), while Group C had better sleep efficacy than Groups A (p =.02) and B (p =.04). Conclusion: Melatonin with sleep deprivation is less effective at inducing sleep than combined chloralhydrate and sleep deprivation. [ABSTRACT FROM AUTHOR]

Abstract Background Chloral hydrate is a sedative-hypnotic drug widely used for relieving fear and anxiety in pediatric patients. However, mechanisms underlying the chloral hydrate-mediated analgesic action remain unexplored. Therefore, we investigated the effect of 2′,2′,2′-trichloroethanol (TCE), the active metabolite of chloral hydrate, on tetrodotoxin-resistant (TTX-R) Na+ channels expressed in nociceptive sensory neurons. Methods The TTX-R Na+ current (INa) was recorded from acutely isolated rat trigeminal ganglion neurons using the whole-cell patch-clamp technique. Results Trichloroethanol decreased the peak amplitude of transient TTX-R INa in a concentration-dependent manner and potently inhibited persistent components of transient TTX-R INa and slow voltage-ramp-induced INa at clinically relevant concentrations. Trichloroethanol exerted multiple effects on various properties of TTX-R Na+ channels; it (1) induced a hyperpolarizing shift on the steady-state fast inactivation relationship, (2) increased use-dependent inhibition, (3) accelerated the onset of inactivation, and (4) retarded the recovery of inactivated TTX-R Na+ channels. Under current-clamp conditions, TCE increased the threshold for the generation of action potentials, as well as decreased the number of action potentials elicited by depolarizing current stimuli. Conclusions Our findings suggest that chloral hydrate, through its active metabolite TCE, inhibits TTX-R INa and modulates various properties of these channels, resulting in the decreased excitability of nociceptive neurons. These pharmacological characteristics provide novel insights into the analgesic efficacy exerted by chloral hydrate.

Objective To establish a quality control method for detecting impurities in chloral hydrate raw materials, improve the quality standards and control limits of raw materials. Methods The determination methods of chloroform and halogenated carboxylic acid in chloral hydrate were established to monitor the change of impurities in chloral hydrate through stability. Results The research and establishment of chloroform and halogenated carboxylic acid methods met the requirements of relevant regulations for analytical methodology verification, which could accurately detect four impurities in raw materials and preparations by one method. Conclusion The study provides technical support for the improvement and optimization of the quality standards of chloral hydrate and preparations. It is very necessary to implement the impurity monitoring in preparation research and production process by the chloral hydrate impurity detection and the stability comparison of this product at high temperature and light, which could largely promote the safety of medication. [ABSTRACT FROM AUTHOR]

Objectives Sedation and stability during electroencephalography (EEG) in pediatrics have high clinical importance. This study compares the sedative properties of oral chloral hydrate (OCH) and intranasal fentanyl (INF). Materials & Methods This study was a randomized clinical trial conducted in 2020 in Isfahan City on sixty-two pediatric candidates for EEG. Patients were randomized into two groups receiving 50 mg/kg OCH and 2 µg/kg INF thirty minutes before the process. The heart rate (HR), mean arterial pressure (MAP), respiratory rate (RR), and oxygen saturation (O2 sat) of patients, sedation, and physician's satisfaction were measured and compared between groups. Results The HR of patients decreased significantly in both groups (P< 0.001), and the patients that received INF had significantly lower HR 15, 30, 45, and 60 minutes after drug administrations (P< 0.05). RR evaluation indicated significantly decreased RR in both groups (P< 0.001), and patients receiving INF had lower RR 30, 45, and 60 per minutes after drug administrations (P< 0.001). Both groups showed significantly increased sedation levels during the study (P< 0.001), and patients treated with INF had higher sedation levels 15, 30, and 45 minutes after drug administration. Satisfaction rates were higher among the group that received INF (P= 0.020). Conclusion The use of INF had significant analgesic and sedative effects on pediatrics undergoing EEG. [ABSTRACT FROM AUTHOR]

Purpose This study investigated correlations between the actual sleep time 24 hours prior to an examination and the time to achieve chloral hydrate sedation in pediatric patients. Methods With parental consent, 84 children who were placed under moderate or deep sedation with chloral hydrate for examinations from November 19, 2020 to July 9, 2022 were recruited. Results Patients' average age was 19.9 months. Pediatric neurology patients and those who underwent electroencephalography took significantly longer to achieve sedation with chloral hydrate. There was a negative correlation between the time to achieve sedation and actual sleep time within 24 hours prior to the examination. Positive correlations were found between the actual sleep time 24 hours prior to the examination and the second dose per weight, as well as between the sedation recovery time and awake hours before the examination. Conclusion Sleep restriction is not an effective adjuvant therapy for chloral hydrate sedation in children, and sedation effects vary according to pediatric patients' characteristics. Therefore, it would be possible to reduce the unnecessary efforts of caregivers who restrict children's sleep for examinations. It is more important to educate parents about safe sedation than about sleep restriction.

Background Most children with facial lacerations require sedation for primary sutures. However, sedation guidelines for invasive treatment are lacking. This study evaluated the current status of the sedation methods used for pediatric facial laceration repair in Korea. Methods We surveyed one resident in each included plastic surgery training hospital using face-to-face interviews or e-mail correspondence. The health care center types (secondary or tertiary hospitals), sedation drug types, usage, and dosage, procedure sequence, monitoring methods, drug effects, adverse events, and operator and guardian satisfaction were investigated. Results We included 45/67 hospitals (67%) that used a single drug, ketamine in 31 hospitals and chloral hydrate in 14 hospitals. All health care center used similar sedatives. The most used drug administered was 5 mg/kg intramuscular ketamine (10 hospitals; 32%). The most common chloral hydrate administration approach was oral 50 mg/kg (seven hospitals; 50%). Twenty-two hospitals (71%) using ketamine followed this sequence: administration of sedatives, local anesthesia, primary repair, and imaging work-up. The most common sequence used for chloral hydrate (eight hospitals; 57%) was local anesthesia, administration of sedatives, imaging work-up, and primary repair. All hospitals that used ketamine and seven (50%) of those using chloral hydrate monitored oxygen saturation. Median operator satisfaction differed significantly between ketamine and chloral hydrate (4.0 [interquartile range, 4.0–4.0] vs. 3.0 [interquartile range, 3.0–4.0]; p

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

Abstract 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

Background: Chloral hydrate is a sedative-hypnotic drug widely used for relieving fear and anxiety in pediatric patients. However, mechanisms underlying the chloral hydrate-mediated analgesic action remain unexplored. Therefore, we investigated the effect of 2′,2′,2′-trichloroethanol (TCE), the active metabolite of chloral hydrate, on tetrodotoxin-resistant (TTX-R) Na+ channels expressed in nociceptive sensory neurons. Methods: The TTX-R Na+ current (INa) was recorded from acutely isolated rat trigeminal ganglion neurons using the whole-cell patch-clamp technique. Results: Trichloroethanol decreased the peak amplitude of transient TTX-R INa in a concentration-dependent manner and potently inhibited persistent components of transient TTX-R INa and slow voltage-ramp-induced INa at clinically relevant concentrations. Trichloroethanol exerted multiple effects on various properties of TTX-R Na+ channels; it (1) induced a hyperpolarizing shift on the steady-state fast inactivation relationship, (2) increased use-dependent inhibition, (3) accelerated the onset of inactivation, and (4) retarded the recovery of inactivated TTX-R Na+ channels. Under current-clamp conditions, TCE increased the threshold for the generation of action potentials, as well as decreased the number of action potentials elicited by depolarizing current stimuli. Conclusions: Our findings suggest that chloral hydrate, through its active metabolite TCE, inhibits TTX-R INa and modulates various properties of these channels, resulting in the decreased excitability of nociceptive neurons. These pharmacological characteristics provide novel insights into the analgesic efficacy exerted by chloral hydrate. [ABSTRACT FROM AUTHOR]

The purpose of this study was to compare the efficacy of oral triclofos (TRI), intranasal midazolam (INM), and intranasal dexmedetomidine (IND) in achieving successful sedation in children undergoing MRI. This open-label, three-arm, randomized trial was conducted in a tertiary care teaching hospital over 18-month period. Children scheduled for MRI were enrolled. Rate of successful/adequate sedation was assessed using the Paediatric Sedation State Scale (PSSS). The primary outcome was the efficacy (successful sedation or sedation rate) of the three drugs. One-hundred and ninety-five children were included for the MRI procedure. IND was found to be superior in terms of achieving successful sedation. INM had a shorter onset and duration of sedation compared to IND and TRI, but with an increased failure rate (88.3%). Keeping INM as the reference group, it was found that the odds of sedation increased 4.1 times on changing from INM to IND (p < 0.01), and 2.26 times on changing from INM to TRI (p < 0.01). Adverse events included nasal discomfort (18.3%) in INM group; and self-limited tachycardia (4.6%) and hypotension (10.8%) in the IND group. Conclusion: IND was more efficacious than INM or TRI for procedural sedation in children undergoing MRI without any significant adverse events. Clinical trial registration: CTRI/2019/01/017257; date registered: 25/01/2019. What is Known: • Oral triclofos (TRI) and intranasal midazolam (INM) have been used for procedural sedation in children undergoing MRI with variable success; but the experience with intranasal dexmedetomidine (IND) is limited. What is New: • IND provides more effective sedation compared to INM or TRI for procedural sedation in children undergoing MRI, without any significant adverse events. [ABSTRACT FROM AUTHOR]

Background: Physiological processes influencing a drugs' efficacy change substantially over the course of the day. However, it is unclear whether there is an association between the sedative success rate of chloral hydrate and the time of day. We conducted a retrospective study of 41,831 cases, to determine if there was a difference in sedation success rate with chloral hydrate in children seen in the morning and afternoon. Methods: Patients who accepted the sedation service were included. Eligible patients were divided into two cohorts of morning and afternoon cases, according to the time of day when the initial dose of chloral hydrate was administered. To ensure that the two groups were comparable, a propensity score matching method was utilized. Results: The success rate with the initial dose of chloral hydrate was higher in patients who received sedation services in the afternoon. In the subgroup analysis, the afternoon cases had a higher sedation success rate compared to the morning cases in male patients; whereas, in female patients, no difference was detected between the morning versus afternoon cases. Conclusions: These results show that the afternoon cases had a higher sedation success rate than the morning cases, despite the afternoon cases receiving relatively lower initial dose than the morning cases. However, the clinical significance remains to be discussed, and further prospective studies are needed to validate the findings. [ABSTRACT FROM AUTHOR]

Trichloroethylene (TCE) triggers a severe hypersensitivity syndrome in the occupational population dependent on dendritic cells (DCs). Chloral hydrate (CH), the major oxidative metabolite of TCE, has been proved to be the culprit causative substance of TCE-induced hypersensitivity by human patch tests. Because redox imbalance is essential for chemical sensitizers-induced maturation of DCs, we predicted that CH would activate DCs by the nuclear factor E2-related factor 2 (Nrf2)-mediated antioxidant response. This study selected THP-1 cells as the in vitro DC model, and we evaluated the cell activation markers, intracellular oxidative stress, and Nrf2 pathway related genes expression in response to CH in THP-1 cells. CH displayed significant stimulation of THP-1 cells activation, including CD54 and CD86 expression, IL-8 release, and cell migration, and damaged the redox balance by triggering ROS generation, GSH consumption, and antioxidase activities modulation. The levels of Nrf2 and its downstream genes (HO-1 and NQO1) in mRNA and protein expressions were upregulated by CH, and CH also promoted the nuclear translocation of Nrf2. Subsequently, we investigated the effects of antioxidant on Nrf2-mediated cell defense in CH treated cells. Pretreatment with curcumin dramatically reduced cell activation and oxidative stress triggered by CH in THP-1 cells. We also confirmed the specific role of Nrf2 in CH-induced cell activation using NRF2-knockout cells. Deficiency of Nrf2 inhibited cell activation and downregulated HO-1 and NQO1 expression in CH-challenged cells. These findings suggest that Nrf2-dependent redox homeostasis plays a pivotal role in CH-induced activation of THP-1 cells, thereby providing new knowledge of the allergen as well as the molecular mechanism involving in TCE-induce hypersensitivity syndrome.

The transmembrane protein TMEM206 was recently identified as the molecular basis of the extracellular proton-activated Cl- channel (PAC), which plays an essential role in neuronal death in ischemia-reperfusion. The PAC channel is activated by extracellular acid, but the proton-sensitive mechanism remains unclear, although different acid-sensitive pockets have been suggested based on the cryo-EM structure of the human PAC (hPAC) channel. In the present study, we firstly identified two acidic amino acid residues that removed the pH-dependent activation of the hPAC channel by neutralization all the conservative negative charged residues located in the extracellular domain of the hPAC channel and some positively charged residues at the hotspot combined with two-electrode voltage-clamp (TEVC) recording in the Xenopus oocytes system. Double-mutant cycle analysis and double cysteine mutant of these two residues proved that these two residues cooperatively form a protonsensitive site. In addition, we found that chloral hydrate activates the hPAC channel depending on the normal pH sensitivity of the hPAC channel. Furthermore, the PAC channel knock-out (KO) male mice (C57BL/6J) resist chloral hydrate-induced sedation and hypnosis. Our study provides a molecular basis for understanding the proton-dependent activation mechanism of the hPAC channel and a novel drug target of chloral hydrate. [ABSTRACT FROM AUTHOR]

The algal organic matter (AOM) is a problem in water treatment. Although the adsorption process is extensively applied to drinking water treatment, little information is known about the potential of new adsorbents to remove AOM. Herein, this work evaluated the removal of AOM and its main compounds (dissolved organic carbon (DOC), carbohydrate, and protein) by new adsorbents—mesoporous silica (SBA-16), graphene oxide material from citric acid (CA), and sugar (SU), and a composite of CA immobilized on sand (GSC). In general, the removal efficiencies followed the order of SBA-16 > CA > SU or GSC for DOC, carbohydrate, and protein. At environmental condition (5 mg DOC·L−1 and pH 8), high removals were reported for SBA-16 (88.8% DOC, 80.0% carbohydrate, and 99.6% protein) and CA (70.0% DOC, 66.7% carbohydrate, and 89.7% protein), while moderate removals were found for SU (60.5% DOC, 47.9% carbohydrate, and 66.5% protein) and GSC (67.4% DOC, 60.8% carbohydrate, and 57.4% protein). Based on these results, further analyses were done with SBA-16 and CA. Both adsorbents' efficiencies decayed with the pH increment of the test water. Disinfection by-products reductions found using SBA-16 — trihalomethanes (58.2 to 94.7%) and chloral hydrate (48.7 to 78.8%) — were higher than the ones using CA—trihalomethanes (45.2 to 82.4%) and chloral hydrate (40.1 to 70.8%). This study showed the potential of applying these adsorbents for AOM removal, and further investigations are suggested to increase the adsorption capacity of these adsorbents. [ABSTRACT FROM AUTHOR]

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 [ABSTRACT FROM AUTHOR]

Background Most children with facial lacerations require sedation for primary sutures. However, sedation guidelines for invasive treatment are lacking. This study evaluated the current status of the sedation methods used for pediatric facial laceration repair in Korea. Methods We surveyed one resident in each included plastic surgery training hospital using face-to-face interviews or e-mail correspondence. The health care center types (secondary or tertiary hospitals), sedation drug types, usage, and dosage, procedure sequence, monitoring methods, drug effects, adverse events, and operator and guardian satisfaction were investigated. Results We included 45/67 hospitals (67%) that used a single drug, ketamine in 31 hospitals and chloral hydrate in 14 hospitals. All health care center used similar sedatives. The most used drug administered was 5 mg/kg intramuscular ketamine (10 hospitals; 32%). The most common chloral hydrate administration approach was oral 50 mg/kg (seven hospitals; 50%). Twenty-two hospitals (71%) using ketamine followed this sequence: administration of sedatives, local anesthesia, primary repair, and imaging work-up. The most common sequence used for chloral hydrate (eight hospitals; 57%) was local anesthesia, administration of sedatives, imaging work-up, and primary repair. All hospitals that used ketamine and seven (50%) of those using chloral hydrate monitored oxygen saturation. Median operator satisfaction differed significantly between ketamine and chloral hydrate (4.0 [interquartile range, 4.0–4.0] vs. 3.0 [interquartile range, 3.0–4.0]; p <0.001). Conclusion The hospitals used various procedural sedation methods for children with facial lacerations. Guidelines that consider the patient's condition and drug characteristics are needed for safe and effective sedation. [ABSTRACT FROM AUTHOR]

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). [ABSTRACT FROM AUTHOR]

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Purpose To assess the use of oral chloral hydrate (CH) sedation in uncooperative children to perform a precise cycloplegic retinoscopy and a thorough dilated fundus examination in an outpatient strabismus and nystagmus clinic. Patients and methods A prospective study was conducted on 114 uncooperative children (119 sedation episodes) who were attending the strabismus and nystagmus outpatient clinic at Menoufia University Hospital. Children were sedated by the first dose of CH (50 mg/kg). A second dose, half-strength of the first dose, was given if no adequate sedation occurred after 30 min. The degree of sedation was graded into five categories: excellent, good, fair, poor, and failure. All demographic characteristics, sedation success, failure, and adverse events were reported and statistically analyzed. Results The mean age of children was 23.38 months (range: 5.16–62.06), and their weight ranged from 6.5 to 22 kg. The total CH dose ranged from 325 to 1500 mg. A total of 78 sedation episodes were reported by a single dose, and 41 by two doses. The percentage of the grade of sedation in our 119 episodes was as follows: excellent (56.3%), good (9.2%), fair (28.6%), poor (2.5%), and failure (3.4%). The overall success of one dose was 65.5%, which increased to 96.6% by a second supplemental dose. The most common complication was vomiting (13.4%). Other complications included prolonged drowsiness (one case) and paradoxical agitation (two cases). Spearman correlation showed a significant positive correlation between the degree of sedation and the total dose of CH (r=0.603, P

Purpose To assess the use of oral chloral hydrate (CH) sedation in uncooperative children to perform a precise cycloplegic retinoscopy and a thorough dilated fundus examination in an outpatient strabismus and nystagmus clinic. Patients and methods A prospective study was conducted on 114 uncooperative children (119 sedation episodes) who were attending the strabismus and nystagmus outpatient clinic at Menoufia University Hospital. Children were sedated by the first dose of CH (50 mg/kg). A second dose, half-strength of the first dose, was given if no adequate sedation occurred after 30 min. The degree of sedation was graded into five categories: excellent, good, fair, poor, and failure. All demographic characteristics, sedation success, failure, and adverse events were reported and statistically analyzed. Results The mean age of children was 23.38 months (range: 5.16–62.06), and their weight ranged from 6.5 to 22 kg. The total CH dose ranged from 325 to 1500 mg. A total of 78 sedation episodes were reported by a single dose, and 41 by two doses. The percentage of the grade of sedation in our 119 episodes was as follows: excellent (56.3%), good (9.2%), fair (28.6%), poor (2.5%), and failure (3.4%). The overall success of one dose was 65.5%, which increased to 96.6% by a second supplemental dose. The most common complication was vomiting (13.4%). Other complications included prolonged drowsiness (one case) and paradoxical agitation (two cases). Spearman correlation showed a significant positive correlation between the degree of sedation and the total dose of CH (r=0.603, P<0.001). Conclusion According to our study, the use of CH was found to have a high success rate with two doses, without major adverse events. [ABSTRACT FROM AUTHOR]

Background: This study aimed to investigate the risk factors for chloral hydrate sedation failure and complications in a tertiary children's hospital in South Korea., Methods: A retrospective analysis of pediatric procedural sedation with chloral hydrate between January 1, 2021, and March 30, 2022, was performed. The collected data included patient characteristics, sedation history, and procedure. Multivariable regression analysis was performed to identify the risk factors for procedural sedation failure and complications., Results: A total of 6,691 procedural sedation were included in the analysis; sedation failure following chloral hydrate (50 mg/kg) occurred in 1,457 patients (21.8%) and was associated with a higher rate of overall complications compared to those with successful sedation (17.5% [225/1457] vs. 6.2% [322/5234]; P < 0.001, odds ratio: 3.236). In the multivariable regression analysis, the following factors were associated with increased risk of sedation failure: general ward or intensive care unit inpatient (compared with outpatient); congenital syndrome; oxygen dependency; history of sedation failure or complications with chloral hydrate; procedure more than 60 min; and magnetic resonance imaging, radiotherapy, or procedures with painful or intense stimuli (all P values < 0.05). Factors contributing to the complications included general ward inpatient, congenital syndromes, congenital heart disease, preterm birth, oxygen dependency, history of complications with chloral hydrate, and current sedation failure with chloral hydrate (all P values < 0.05)., Conclusions: To achieve successful sedation with chloral hydrate, the patient's sedation history, risk factors, and the type and duration of the procedure should be considered.