Effects Of Chloral Hydrate Research Articles

Effects of Chloral Hydrate on the Morphogenetic Characteristics of the Neocortex and Functional Status in Elderly Male Rats

Effects of Chloral Hydrate on the Morphogenetic Characteristics of the Neocortex and Functional Status in Elderly Male Rats

Safety and Effectiveness of Chloral Hydrate in Auditory Brainstem Response Tests: A Single-Center and Cross-Sectional Study

Safety and Effectiveness of Chloral Hydrate in Auditory Brainstem Response Tests: A Single-Center and Cross-Sectional Study

Effectiveness of Chloral Hydrate on Brain MRI in Children with Developmental Delay/Intellectual Disability Comparing with Normal Intelligence: Single Tertiary Center Experience.

Neurodiagnostic investigation requirements are expanding for diagnostic and therapeutic purposes in children, especially in those with developmental delay/intellectual disability (DD/ID). Thus, determination of optimal sedatives to achieve successful sedation and immobility without further neurological compromise is important in children with DD/ID. The purpose of this study is to assess the effectiveness and adverse reactions of chloral hydrate (CH) for brain magnetic resonance imaging (B-MRI) in children with DD/ID compared to those with normal intelligence (NI). We performed a retrospective chart review of children aged from 1 day to 12 years who required elective sedation using CH for B-MRI. About 730 cases (415 with DD/ID and 315 with NI) of CH sedation were conducted for B-MRI. Children with DD/ID showed a higher failure rate (22%) than did those with NI (6%); additional CH and prolonged sedation time were required. There was no difference in incidence of adverse reactions between DD/ID and NI groups (p = 0.338). Older or heavier children with DD/ID (p = 0.036 and p = 0.013, respectively), as well as those diagnosed with epilepsy or neuropsychiatric disorders showed higher risk of sedation failure (p < 0.001 for each). In conclusion, CH was a suboptimal sedative drug for children with DD/ID compared with those with NI. Other alternative or supplementary sedatives should be taken into consideration especially for those vulnerable groups.

The Comparison between Effect of Chloralhydrate and Diphenhydramine on Sedating for Electroencephalography.

Electroencephalography (EEG) is the most effective diagnostic tool in distinguishing epileptic seizure. Chloral hydrate (CH) is a sedative hypnotic drug, commonly used as a method of sedation in children aged<3 yr. Furthermore, diphenhydramine (DH) is a first generation antihistaminic drug (H1 receptor blocker) with anti-cholinergic effect. In this study, we aimed to compare the effects of CH and DH on sedating for EEG. This retrospective cohort study was conducted on patients' records of aged 15-72 months undergone an EEG and required sedation. Overall, 200 children were assessed including 100 patients in group 1 (CH) and 100 patients in group 2 (DH). Data were gathered by a form including age, sex, the cause of EEG, complication, success rate, first dose success, as well as sleep and awake latency. Data were reported by descriptive statistics (mean, standard deviation, number, and percent) and analyzed by t-test and chi-square using SPSS 19. Totally, 113(56%) male patients with the mean age of 35.62±14.00 months participated in this study. Vomiting and agitation were the most frequent complications in CH and DH groups, respectively. Most of patients in both group indicated successful sedation. CH indicated higher rate of success by first dose toward DH. In addition, CH mentioned lower sleep latency and significant difference was noted between groups. The mean duration of awake latency was higher in DH groups which showed significant difference. CH might be a more effective drug in comparison with the DH for sedation. According to the availability and low cost of DH, investigators are advised to perform further investigations.

Chloral hydrate-dependent reduction in the peptidoglycan-induced inflammatory macrophage response is associated with lower expression levels of toll-like receptor 2.

The aim of this study was to investigate the effect and mechanism of action of chloral hydrate on the peptidoglycan (PGN)-induced inflammatory macrophage response. The effect of chloral hydrate on the production of tumor necrosis factor α (TNF-α) and interleukin-6 (IL-6) by murine peritoneal macrophages with PGN-stimulation was investigated. In addition, RAW264.7 cells transfected with a nuclear factor-κB (NF-κB) luciferase reporter plasmid stimulated by PGN were used to study the effect of chloral hydrate on the levels NF-κB activity. Flow cytometry and western blotting were performed to investigate the expression levels of toll-like receptor 2 (TLR2) in the treated RAW264.7 cells. It was identified that chloral hydrate reduced the levels of IL-6 and TNF-α produced by the peritoneal macrophages stimulated with PGN. The levels of NF-κB activity of the RAW264.7 cells stimulated by PGN decreased following treatment with chloral hydrate, which was associated with a reduction in the expression levels of TLR2 and reduced levels of TLR2 signal transduction. These data demonstrate that chloral hydrate reduced the magnitude of the PGN-induced inflammatory macrophage response associated with lower expression levels of TLR2.

Utilisation of an outpatient sedation unit in paediatric ophthalmology: safety and effectiveness of chloral hydrate in 1509 sedation episodes

ObjectiveTo report the largest study on the safety and effectiveness of sedation in paediatric ophthalmology in a nurse-led outpatient sedation unit.DesignRetrospective cohort study reviewing all children who underwent sedation from...

The effect of chloral hydrate on the metabolism of ethanol in mice.

The effect of chloral hydrate on the metabolism of ethanol in mice.

Effect of chloral hydrate and related compounds on the activity of several enzymes in extracts of rumen microorganisms.

Summary The effect of chloral hydrate, halogenated aldehydes and methanes on the activity of several enzymes in extracts of rumen microorganisms was examined. The halogenated compounds used, except bromal, had only a slight if any effect on either lactic dehydrogenase, acetokinase, phosphotransacetylase or succinic dehydrogenase. However, alcoholdehydrogenase, pyruvate decarboxylase and also the non-enzymatic model reaction for pyruvate decarboxylation were clearly inhibited. An explanation of this effect is proposed, based on electronic delocalization in the intermediary coenzyme complexes. Zusammenfassung Der Einfluß von Chloralhydrat und verwandter Verbindungen auf die Enzyme-Aktivität von Extrakten ruminaler Mikroorganismen Es wurde die Wirkung von Chloralhydrat sowie halogenierter Aldehyde und Methane auf die Enzymaktivität von Pansenmikrobenextrakten untersucht. Die Halogenverbindungen hatten — vom Bromal abgesehen — nur einen geringen oder keinen Einfluß auf die Milchsäuredehydrogenase, Acetkinase, Phosphotransacetylase und Bernsteinsäuredehydrogenase. Die Alkohol-dehydrogenase, Brenztraubensäuredecarboxylase sowie die Nichtenzymatische Modellreaktion der Brenztraubensäure-Decarboxylierung waren hingegen deutlich gehemmt. Das Phänomen wird durch Annahme einer Elektronendislokation im intermediären Coenzym-Komplex zu erklären versucht. Résumé L'influence de l'hydrate de chloral et des composés apparentés sur l'activité enzymatique des extraits de microorganismes du rumen On examine l'effet de l'hydrate de chloral, de même que des aldéhydes et des méthanes halogénés, sur l'activité enzymatique des extraits de microorganismes du rumen. A l'exception du bromal, les composés halogénés n'ont aucune influence ou qu'une influence faible sur les déhydrogénases lactiques, les acéto-kinases, les trans-acétylases phosphoriques et les déhydrogénases succiniques. Par contre, les déhydrogénases alcooliques, les décarboxylases pyruviques, de même que le schéma de decarboxylation pyruvique non enzymatique sont nettement inhibés. On tente d'expliquer ce phénomène en envisageant une dislocation des électrons dans le complexe coenzymatique intermédiaire. Resumen Efecto del hidrato de cloral y compuestos similares sobre la actividad de varias enzimas en extractos de microorganismos ruminates Se examinó el efecto del hidrato de cloral, aldehidos y metanos halogenados sobre la actividad enzimática de extractos de microorganismos de la panza. Los compuestos halogenados usados — excepción hecha con el bromal — solo ejercían un efecto discreto o nulo sobre la dehidrogenase láctica, aceto-quinasa, fosfotransacetilasa y la dehidrogenasa succínica. Sin embargo, la alcoholdehidrogenase, la decarboxilasa pirúvica y también la reacción modelo no enzimática de la decarboxilación pirúvica fueron inhibidas de forma manifiesta. Se intenta explicar este fenómeno, admitiendo la dislocación electrónica en los complejos coenzimáticos intermediarios.

The effect of chloral hydrate on the in-vitro T3 binding to adult rat cerebral nuclei

Chloral hydrate is a widely used hypnotic drug for children and animals but the possible interactions of its sedative action and thyroid hormones has not been investigated. In this study the effect of chloral hydrate on the in-vitro binding of triiodothyronine (T3) to cerebral nuclei of adult rats and on the thyroid hormones' synaptosomal and plasma availability were examined. Our results show that during deep anaesthesia caused by a single intraperitoneal administration of chloral hydrate (100 mg kg(-1)), the maximal number of nuclear thyroid hormone receptors (Bmax) and the equilibrium dissociation constant (Kd) were decreased. These changes returned to normal values when rats woke up (2(1/2)h after chloral hydrate administration). Plasma or synaptosomal levels of thyroid hormones were unaffected during chloral hydrate treatment. Our study demonstrates that the nuclear T3 binding in adult rat brain is affected by the sedative action of chloral hydrate.

Sleep/Sedation in Children Undergoing EEG Testing: A Comparison of Chloral Hydrate and Music Therapy

ABSTRACT.This study included a total of 60 pediatric patients ranging from 1 month through 5 years of age. The effects of chloral hydrate and music therapy were evaluated and compared as means of safe and effective ways to achieve sleep/sedation in infants and toddlers undergoing EEG testing. The results of the study indicate that music therapy may be a cost-effective, risk-free alternative to pharmacological sedation.

Short-Term Chloral Hydrate Administration and Cancer in Humans

Chloral hydrate, used as a hypnosedative in adults and children, has been shown to be genotoxic and carcinogenic in animal studies. We investigated the potential causal association between chloral hydrate exposure and cancer risk in humans. Cancer incidence was previously determined via biennial screening analyses of the 215 most commonly used drugs between 1976 and 1998 for a cohort of 143,574 outpatients at Kaiser Permanente who had prescriptions filled between 1969 and 1973. Among users of chloral hydrate, statistically significant elevations in standardised morbidity ratios were observed during various years for cancer at five anatomical sites, including the lung, stomach, prostate, skin melanoma and mouth floor. In this analysis, these associations were investigated using: (i) a dose-response analysis among exposed subjects; and (ii) a two-stage design with exposed and non-exposed persons. There was evidence of an increasing risk of prostate cancer with increasing number of dispensings of chloral hydrate, which persisted after controlling for benign prostatic hypertrophy, vasectomy and obesity; however, the trend was not statistically significant. There was no evidence of a dose-response relationship between chloral hydrate and risk of any of the other four cancers. In the two-stage design, analyses comparing exposed and unexposed subjects showed no increased risk of cancer after controlling for confounding variables; however, the data were suggestive for prostate cancer, where the increased risk associated with chloral hydrate exposure after adjustment for confounding variables persisted. No dose-response relationship was seen for any of the other four cancer sites. To our knowledge, this is the first study to examine the relationship between chloral hydrate exposure and cancer risk in humans. There was no persuasive evidence to support a causal relationship between chloral hydrate exposure in humans and the development of cancer. However, statistical power was low for weak associations, particularly for some of the individual cancer sites. Although animal data using much higher doses of chloral hydrate have demonstrated its genotoxicity and carcinogenicity, the effects of chloral hydrate in humans are still uncertain.

Sleep/Sedation in Children Undergoing EEG Testing: A Comparison of Chloral Hydrate and Music Therapy

This study included a total of 60 pediatric patients ranging from 1 month through 5 years of age. The effects of chloral hydrate and music therapy were evaluated and compared as means of safe and effective ways to achieve sleep/sedation in infants and toddlers undergoing EEG testing. The results of the study indicate that music therapy may be a cost-effective, risk-free alternative to pharmacological sedation.

Trichloroethanol alters action potentials in a subgroup of primary sensory neurones.

We investigated the effects of 2,2,2-trichloroethanol (TCE), the active metabolite of chloral hydrate, on large-conductance calcium-activated K+ channels (BKCa channels) of dorsal root ganglion (DRG) neurones. In outside-out patches, 2 and 5 mM TCE increased the open probability of BKCa channels to 1.7-fold and 2.8-fold of control, respectively. In 50% of the cells investigated (group A) the action potential (AP) was shortened reversibly by TCE by 20% and the whole-cell outward-current was increased by 44%. Both effects could be antagonized by iberiotoxin. In a second group of neurone (group B), TCE prolonged the AP duration. The effects of TCE in group A, which was 20-fold more potent than ethanol on BKCa channels and AP might contribute to the described analgesic effect of chloral hydrate.

Biochemical effects of chloral hydrate on male rats following 7-day drinking water exposure.

The biochemical and toxicological effects of chloral hydrate were investigated. Four groups (n = 7 per group) of male Sprague-Dawley rats (161-170 g) were administered chloral hydrate in drinking water at concentrations of 20, 200 or 2000 ppm for 7 days. The control group received phosphate-buffered water only. There were no treatment-related changes in the body weight gains, relative weights of major organs or haematological parameters. Trichloroacetic acid was significantly (P < 0.05) elevated in the serum of high-dose animals (7.75 +/- 5.14 mg dl(-1), mean +/- SD). In the high-dose animals there was a 36% increase in protein level in the liver homogenates but not in the corresponding 9000 g supernatants. Concurrently, there was a threefold increase in the activity of the hepatic peroxisomal enzyme palmitoyl CoA oxidase (PCO). A prominent change was the dose-related suppression in hepatic aldehyde dehydrogenase (ALDH) activity observed in all treatment groups, with the decrease ranging from 15% at 20 ppm to 68% at 2000 ppm. There were no significant decreases in the activity of hepatic enzymes ethoxyresorufin O-deethylase (EROD), benzyloxyresorufin O-dealkylase (BROD) and UDP-glucuronosyl-transferase (UDPGT). In the high-dose group there was a 30% increase in hepatic glutathione-S transferase (GST) activity, accompanied by a 13% increase in glutathione (GSH). Significant effects on lipids were observed in the liver of the high-dose animals, with a 15% decrease in hepatic cholesterol and triglyceride levels. There were no treatment-related changes in serum chemistry parameters, including cholesterol and triglyceride levels. Although in vitro assays showed chloral hydrate to be an inhibitor of serum pseudocholinesterase activity, with a 50% inhibition concentration (ic(50)( of approximately 0.7 mM at 5 mM butyrylthiocholine, no decrease in serum pseudocholinesterase activity was found in the treated animals. It was concluded that the liver is the target organ for chloral hydrate, with suppression of ALDH as the most sensitive endpoint followed by alteration in the GSH level and GST activity. Changes observed in the high-dose animals, such as increased peroxisomal PCO activity in the liver and perturbation of lipid homeostasis in the liver and blood, were likely to be associated with trichloracetic acid, the major metabolite of chloral hydrate.

Inhibition by chloral hydrate and trichloroethanol of AMPA-induced Ca 2+ influx in rat cultured cortical neurones

The effects of chloral hydrate and its main metabolite 2,2,2-trichloroethanol were investigated on the ( S)-α-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA)-induced rise of intracellular Ca 2+ concentration ([Ca 2+] i) in cultured non-pyramidal cortical neurones of rats by using single-cell fura-2 microfluorimetry. AMPA elicited a concentration-dependent effect that peaked at 300 μM (EC 50, 7.5 μM). Responses to AMPA (30 μM) were markedly inhibited by superfusion with chloral hydrate (IC 50, 4.5 mM) or trichloroethanol (IC 50, 0.9 mM). By contrast, ethanol (100 mM) caused only slight inhibition. In conclusion, the results demonstrate that chloral hydrate and especially its metabolite trichloroethanol, inhibit the AMPA-induced rise of [Ca 2+] i by depressing the entry of Ca 2 into cortical neurones via the AMPA receptor-channel.

Effect of chloral hydrate on in vivo KCl-induced striatal dopamine release in the rat.

The release of striatal dopamine (DA) and its metabolites in response to locally-induced K+ depolarization was investigated in vivo in chloral hydrate-anesthetized and freely moving rats. KCl at concentrations of 30, 50, and 100 mM induced significant dose-dependent increases in extracellular DA overflow in both chloral hydrate-anesthetized and freely moving rats (P < 0.05). Extracellular levels of dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA), and 5-hydroxyindoleacetic acid (5-HIAA) were decreased. The DA overflow in response to 30 mM KCl stimulation in anesthetized rats was significantly greater than that in freely moving rats (P < 0.05). In addition, chloral hydrate anesthesia resulted in a significant decrease in extracellular levels of DOPAC and significant increases in extracellular levels of HVA and 5-HIAA in comparison with freely moving rats (P < 0.05). Furthermore, the basal level of extracellular HVA in chloral hydrate-anesthetized rats was significantly higher than that in freely moving rats. These results suggest that chloral hydrate anesthesia could have significant effects on the pharmacological response of the striatal dopaminergic neurons.

Effect of Chloral Hydrate on Sedation and Arterial Oxygen Saturation in Children with Congenital Heart Disease

Effect of Chloral Hydrate on Sedation and Arterial Oxygen Saturation in Children with Congenital Heart Disease

Micronuclei induced in round spermatids of mice after stem-cell treatment with chloral hydrate: evaluations with centromeric DNA probes and kinetochore antibodies.

The chromosomal effects of chloral hydrate (CH) on germ cells of male mice were investigated using two methods to detect and characterize spermatid micronuclei (SMN); (a) anti-kinetochore immunofluorescence (SMN-CREST) and (b) multicolor fluorescence in situ hybridization with DNA probes for centromeric DNA and repetitive sequences on chromosome X (SMN-FISH). B6C3F1 mice received single intraperitoneal (i.p.) injections of 82.7, 165.4, or 413.5 mg/kg and round spermatids were sampled at three time intervals representing cells treated in late meiosis, early meiosis, or as spermatogonial stem cells. No increases in the frequencies of SMN were detected for cells treated during meiosis using either SMN-CREST or SMN-FISH methods. After spermatogonial stem-cell treatment, however, elevated frequencies of SMN were detected by both methods. With SMN-FISH, dose trends were observed both in the frequencies of spermatids containing micronuclei and in the frequency of spermatids carrying centromeric label. These findings corroborate the recent report by Allen and colleagues [Allen JW et al.(1994): Mutat. Res. 323:81-88] that CH treatment of spermatogenic stem cells induced SMN. Furthermore, our findings suggest that chromosomal malsegregation or loss may occur in spermatids long after CH treatment of stem cells. Further studies are needed to understand the mechanism of action of the CH effect on stem cells and to determine whether similar effects are induced in human males treated with CH.

Chloral Hydrate: A Potential Carcinogen

The long-term health effects of chloral hydrate are discussed and its carcinogenicity in mice are reported from the University of California, Davis, and the California School of Public Health, Berkeley.

The effect of chloral hydrate and its metabolites, trichloroethanol and trichloroacetic acid, on bilirubin-albumin binding.

Chloral hydrate is used as a sedative in infants requiring ventilatory support. The metabolites, trichloroethanol and trichloroacetic acid, accumulate in the serum and are protein bound. The possibility that these chemicals might compete with bilirubin for albumin binding was tested using the peroxidase method and a dialysis rate method. Chloral hydrate and trichloroethanol had no effect on bilirubin-albumin binding. Trichloroacetic acid affects bilirubin-albumin binding but to a degree that would be dangerous only in infants with an unusual accumulation of this metabolite.