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

BACKGROUND: 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 used the standard search strategy of the Cochrane Epilepsy Group. We searched MEDLINE (OVID SP) (1950 to July 2017), the Cochrane Central Register of Controlled Trials (CENTRAL) (the Cochrane Library, Issue 7, 2017), Embase (1980 to July 2017), and the Cochrane Epilepsy Group Specialized Register (via CENTRAL) using a combination of keywords and MeSH headings. SELECTION CRITERIA: We included randomised controlled trials that assessed chloral hydrate agent against other sedative agent(s), non-drug agent(s), or placebo for children undergoing non-invasive neurodiagnostic procedures. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed the studies for their eligibility, extracted data, and assessed risk of bias. Results were expressed in terms of risk ratio (RR) for dichotomous data, mean difference (MD) for continuous data, with 95% confidence intervals (CIs). MAIN RESULTS: We included 13 studies with a total of 2390 children. The studies were all conducted in hospitals that provided neurodiagnostic services. Most studies assessed the proportion of sedation failure during the neurodiagnostic procedure, time for adequate sedation, and potential adverse effects associated with the sedative agent.The methodological quality of the included studies was mixed, as reflected by a wide variation in their 'Risk of bias' profiles. Blinding of the participants and personnel was not achieved in most of the included studies, and three of the 13 studies had high risk of bias for selective reporting. Evaluation of the efficacy of the sedative agents was also underpowered, with all the comparisons performed in single small studies.Children who received oral chloral hydrate had lower sedation failure when compared with oral promethazine (RR 0.11, 95% CI 0.01 to 0.82; 1 study, moderate-quality evidence). Children who received oral chloral hydrate had a higher risk of sedation failure after one dose compared to those who received intravenous pentobarbital (RR 4.33, 95% CI 1.35 to 13.89; 1 study, low-quality evidence), but after two doses there was no evidence of a significant difference between the two groups (RR 3.00, 95% CI 0.33 to 27.46; 1 study, very low-quality evidence). Children who received oral chloral hydrate appeared to have more sedation failure when compared with music therapy, but the quality of evidence was very low for this outcome (RR 17.00, 95% CI 2.37 to 122.14; 1 study). Sedation failure rates were similar between oral chloral hydrate, oral dexmedetomidine, oral hydroxyzine hydrochloride, and oral midazolam.Children who received oral chloral hydrate had a shorter time to achieve adequate sedation when compared with those who received oral dexmedetomidine (MD -3.86, 95% CI -5.12 to -2.6; 1 study, moderate-quality evidence), oral hydroxyzine hydrochloride (MD -7.5, 95% CI -7.85 to -7.15; 1 study, moderate-quality evidence), oral promethazine (MD -12.11, 95% CI -18.48 to -5.74; 1 study, moderate-quality evidence), and rectal midazolam (MD -95.70, 95% CI -114.51 to -76.89; 1 study). 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-quality evidence) and intranasal midazolam (MD 12.83, 95% CI 7.22 to 18.44; 1 study, moderate-quality evidence).No data were available to assess the proportion of children with successful completion of neurodiagnostic procedure without interruption by the child awakening. Most trials did not assess adequate sedation as measured by specific validated scales, except in the comparison of chloral hydrate versus intranasal midazolam and oral promethazine.Compared to dexmedetomidine, chloral hydrate was associated with a higher risk of nausea and vomiting (RR 12.04 95% CI 1.58 to 91.96). No other adverse events were significantly associated with chloral hydrate (including behavioural change, oxygen desaturation) although there was an increased risk of adverse events overall (RR 7.66, 95% CI 1.78 to 32.91; 1 study, low-quality evidence). AUTHORS' CONCLUSIONS: The quality of evidence for the comparisons of oral chloral hydrate against several other methods of sedation was very variable. Oral chloral hydrate appears to have a lower sedation failure rate when compared with oral promethazine for children undergoing paediatric neurodiagnostic procedures. The sedation failure was similar for other comparisons such as oral dexmedetomidine, oral hydroxyzine hydrochloride, and oral midazolam. When compared with intravenous pentobarbital and music therapy, oral chloral hydrate had a higher sedation failure rate. However, it must be noted that the evidence for the outcomes for the comparisons of oral chloral hydrate against intravenous pentobarbital and music therapy was of very low to low quality, therefore the corresponding 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 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 the risk of major adverse effects such as bradycardia, hypotension, and oxygen desaturation.

[Preclinical safety evaluation of chloral hydrate after topical application using the example of psoriatic itch]. / Präklinische Validierung der Sicherheit von Chloralhydrat zur topischen Applikation am Beispiel des psoriatischen Pruritus.

BACKGROUND: Psoriasis is known today as a T­cell-mediated autoimmunological systemic disease. The chronic inflammatory processes involve neuroimmunological factors that are held responsible not only for various aspects of psychiatric-neurological comorbidities but also for neurosensory problems, primarily itching. Amongst other things, the significance of GABAA receptors are often discussed in this context. The topical use of chloral hydrate in semisolid preparations for antipruritic therapy goes back to Neisser and is currently experiencing a revival in individually manufactured formulations. However, it is currently unknown whether the unwanted side effects that are described for systemic use of chloral hydrate are also relevant for topical application. OBJECTIVES: For lack of clinical safety data, preclinical tests for cutaneous cytotoxicity and calculations for systemic bioavailability after topical application have been performed. CONCLUSION: The present data cannot fully remove safety concerns for topical application of chloral hydrate in the formulation favoured by the NRF (Neues Rezepturformularium)-the so-called 1­2-3-cream. A twice daily use of the 1­2-3-cream on a maximum of 10% of the body surface can be regarded as safe. For a better assessment of harmlessness, tests for cutaneous bioavailability (concentration-time profile) on human skin and clinical studies would be necessary.

Status dystonicus: a practice guide.

Status dystonicus is a rare, but life-threatening movement disorder emergency. Urgent assessment is required and management is tailored to patient characteristics and complications. The use of dystonia action plans and early recognition of worsening dystonia may potentially facilitate intervention or prevent progression to status dystonicus. However, for established status dystonicus, rapidly deployed temporizing measures and different depths of sedation in an intensive care unit or high dependency unit are the most immediate and effective modalities for abating life-threatening spasms, while dystonia-specific treatment takes effect. If refractory status dystonicus persists despite orally active anti-dystonia drugs and unsuccessful weaning from sedative or anaesthetic agents, early consideration of intrathecal baclofen or deep brain stimulation is required. During status dystonicus, precise documentation of dystonia sites and severity as well as the baseline clinical state, using rating scales and videos is recommended. Further published descriptions of the clinical nature, timing of evolution, resolution, and epidemiology of status dystonicus are essential for a better collective understanding of this poorly understood heterogeneous emergency. In this review, we provide an overview of the clinical presentation and suggest a management approach for status dystonicus.

Pain score assessment in babies undergoing laser treatment for retinopathy of prematurity under sub-tenon anaesthesia.

PURPOSE: To assess the tolerability and outcomes of laser treatment for retinopathy of prematurity (ROP) under sub-tenon anaesthetic with oral or rectal sedation using a reliable, multidimensional, and internationally accepted tool for assessment of neonatal pain. METHODS: Sixty-two babies have had ROP laser treatment in our neonatal unit in the 7-year interval between 1 March 2005 and 28 February 2012; 44% (27 of the 62) were performed using sub-tenon anaesthesia. Pain scores were routinely assessed using the Neonatal Pain Agitation and Sedation Scale (N-PASS) every 10 min during laser treatment. The outcome and requirement for re-treatment in this group was compared with that in the intravenous sedation group. RESULTS: Pain scores were available in 19 of the 27 babies treated under sub-tenon anaesthesia. The mean pain score during treatment was 2.7 (SD ± 1.7, range 0.5-6.2). There was no statistically significant correlation between the mean pain score and duration of treatment (Spearman correlation coefficient (ρ) = 0.31; P = 0.09), number of laser burns (ρ = 0.32; P = 0.09), or post-menstrual age of the baby at the time of treatment (ρ = 0.38; P = 0.052). Treatments performed under sub-tenon anaesthesia were as successful as those performed under intravenous sedation. The mean pain scores during laser treatment under sub-tenon anaesthesia in our study were lower than those previously reported during ROP screening or heel-stick procedure.Conclusion Our study demonstrated that sub-tenon anaesthesia with oral or rectal sedation provides sufficient pain control for laser treatment for ROP without the need or risks of intravenous sedation and intubation.

Central venous cutdown in neonates: feasibility as a bedside procedure without general anesthesia.

BACKGROUND/PURPOSE: A silicone central venous catheter (CVC) is usually inserted using a percutaneous technique under general anesthesia. However, there are numerous reports on the postoperative adverse effects of general anesthesia in neonates. The aim of this study is to investigate the feasibility of open surgical cutdown (OSC) for central venous access without general anesthesia. METHODS: The medical records of patients who underwent OSC at bedside under sedation and local anesthesia were reviewed. Chloral hydrate (100mg/kg) was given orally for the induction of moderate to deep sedation 15 minutes before OSC; then the operative field was infiltrated with 1% lidocaine. When adequate sedation was not achieved, a bolus of phenobarbital (20mg/kg) was given intravenously. RESULTS: Thirteen Broviac lines were inserted into 12 patients. At insertion, the median gestational age was 29 weeks, birth weight was 1,140 g and age was 33 days. No patients required invasive ventilator care; 7 patients received nasal non-invasive ventilator care. Neither intubation nor inotropics were required during the intra- or postoperative period and no perioperative surgical complications occurred. The median catheter duration was 19.5 days. CONCLUSION: OSC at bedside for CVC insertion, using adequate sedation and local anesthesia, is a feasible procedure in neonates.

Anterior sub-Tenon's anesthesia for the treatment of retinopathy of prematurity.

The authors describe a technique of combined oral chloral hydrate and sub-Tenon's anesthesia that is simple, avoids the risks of general anesthesia, and provides superior anesthesia to topical agents alone.

Sedative effect of oral diazepam and chloral hydrate in the dental treatment of children.

PURPOSE: The purpose was to evaluate two sedation protocols during dental sessions in anxious children. MATERIALS AND METHODS: It was a randomized and double-blind study, with each individual being his/her own control within each protocol. Furthermore, the two protocols were compared. Twenty children (36 to 84 months old) who exhibited "definitely negative" behavior according to the Frankl scale were assigned to receive oral chloral hydrate (40 mg/kg) (Group I) or Diazepam (5 mg) (Group II). Behavior during local anesthesia, application of rubber dam, cavity preparation, restorative procedures was evaluated, considering the degree of sleep, body movement, crying and overall behavior. Vital signs were assessed at three different times. The Wilcoxon, Mann-Whitney, Exact Fisher's and Spearman correlation tests were used to analyze the data. RESULTS: Group I presented higher scores for sleep during the CH session than placebo session during rubber dam application (P = 0.0431) and restoration (P = 0.0431). In Group II there was no statistically significant difference (p > 0.05). There were no statistically significant differences between sessions and groups in the evaluation of body movement, crying and vital signs. Overall behavior in the placebo session was better than in the CH session during local anesthesia, but there was no difference between the two drug regimens. There was influence of age during anesthesia and cavity preparation in Group I and during rubber dam application in Group II. It was concluded that oral diazepam and chloral hydrate had no influence on the behavior management for dental treatment with the studied sample.

Functional magnetic resonance imaging of hearing-impaired children under sedation before cochlear implantation.

OBJECTIVE: To investigate functional magnetic resonance imaging (fMRI) in pediatric cochlear implantation candidates with residual hearing who are under sedation for evaluation of auditory function. DESIGN: During fMRI, subjects heard a random sequence of tones (250-4000 Hz) presented 10 dB above hearing thresholds. Tones were interleaved with silence in a block-periodic fMRI design with 30-second on-off intervals. Twenty-four axial sections (5 mm thick) covering most of the brain were obtained every 3 seconds for a total acquisition time of 5.5 minutes. SETTING: Single tertiary academic medical institution. PATIENTS: Severely to profoundly hearing-impaired children (n=10; mean age, 49.1 months). During fMRI, subjects were awake (n=2) or sedated with pentobarbital sodium if their weight was 10 kg or greater (n=4) or chloral hydrate if their weight was less than 10 kg (n=4). MAIN OUTCOME MEASURES: Detection of brain activation by fMRI in the primary auditory cortex (A1) in hearing-impaired patients under sedation, and correlation of A1 activation with hearing levels measured after cochlear implantation. RESULTS: In most subjects, fMRI detected significant levels of activation in the A1 region before cochlear implantation. The improvement in hearing threshold after cochlear implantation correlated strongly (linear regression coefficient, R=0.88) with the amount of activation in the A1 region detected by fMRI before cochlear implantation. CONCLUSIONS: Functional MRI can be considered a means of assessing residual function in the A1 region in sedated hearing-impaired toddlers. With improvements in acquisition, processing, and sedation methods, fMRI may be translated into a prognostic indicator for outcome after cochlear implantation in infants.

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.

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.

[Application of conscious sedation in infants undergoing the auditory brainstem responses (ABR) examination]. / Zastosowanie sedacji plytkiej u niemowlat w przygotowaniu do badania potencjalów sluchowych z pnia mózgu (ABR).

Results of ABR examination in infants undergone the hearing screening examinations were presented. Since February 2004 the group of 184 children were examined. In 29 of them (15.8%) there was a need of further hearing examination using evoked auditory brainstem responses. In 20 of them the examination was done in sleep induced by 6% chloral hydrate enema. The process of sleep was normal and no disturbances of breathing or circulatory systems were observed. The obtained responses from brainstem were not interfered by any artifacts and basic waves were legible and easy for interpretation. Correct results of the ABR examination were obtained in 21/29 (72%) children, while in 7/28 (24%) various degree of hearing losses were detected. Those children were referred for hearing rehabilitation to the Third Degree of Reference Center. It was emphasized in the study that results of ABR examination after conscious sedation induced by 6% chloral hydrate enema accounted the suggestion for its wider use in other clinical and hospital center.

Subchronic toxicity of chloral hydrate on rats: a drinking water study.

The subchronic toxicity of chloral hydrate, a disinfection byproduct, was studied in rats following 13 weeks of drinking water exposure. Male (262 +/- 10 g) and female (190 +/- 8 g) Sprague-Dawley rats, ten animals per group, were administered chloral hydrate via drinking water at 0.2, 2, 20 and 200 ppm. Control animals received distilled water only. Gross and microscopic examinations, serum chemistry, hematology, biochemical analysis, neurogenic amine analysis and serum trichloroacetic acid (TCA) analysis were performed at the end of the treatment period. Bronchoalveolar fluids were collected at necropsy and urine specimens were collected at weeks 2, 6 and 12 for biochemical analysis. No treatment-related changes in food and water intakes or body weight gains were observed. There were no significant changes in the weights of major organs. Except for a mild degree of vacuolation within the myelin sheath of the optic nerves in the highest dose males, there were no notable histological changes in the tissues examined. Statistically significant treatment-related effects were biochemical in nature, with the most pronounced being increased liver catalase activity in male rats starting at 2 ppm. Liver aldehyde dehydrogenase (ALDH) was significantly depressed, whereas liver aniline hydroxylase activity was significantly elevated in both males and females receiving the highest dose. A dose-related increase in serum TCA was detected in both males and females starting at 2 ppm. An in vitro study of liver ALDH confirmed that chloral hydrate was a potent inhibitor, with an IC(50) of 8 micro M, whereas TCA was weakly inhibitory and trichloroethanol was without effect. Analysis of brain biogenic amines was conducted on a limited number (n = 5) of male rats in the control and high dose groups, and no significant treatment-related changes were detected. Taking into account the effect on the myelin sheath of male rats and the effects on liver ALDH and aniline hydroxylase of both males and females at the highest dose level, the no-observed-effect level (NOEL) was determined to be 20 ppm or 1.89 mg kg(-1) day(-1) in males and 2.53 mg kg(-1) day(-1) in females. This NOEL is ca. 1000-fold higher than the highest concentration of chloral hydrate reported in the municipal water supply.

Sedation for pediatric diagnostic imaging: use of pediatric and nursing resources as an alternative to a radiology department sedation team.

OBJECTIVE: To develop a pathway to provide safe, effective, and efficient sedation for pediatric diagnostic imaging studies using non-radiology personnel. MATERIALS AND METHODS: A multidisciplinary team considered manpower and training requirements and national sedation standards before designing a sedation pathway, which included scheduling, pre-sedation history and physical, medication protocols, and monitoring. Oral and IV medication protocols were developed based on patient age and weight. Sedation delays were defined as >15 min (IV) or >30 min (PO) from start of sedation to start of imaging. A sedation failure resulted in an incomplete diagnostic imaging study. Failure rates of 124 sedations before and 388 sedations after the pathway were compared. RESULTS: The sedation failure rate for 7 months prior to pathway initiation was 15% (19/124). In the first 25 months after pathway initiation, failures were significantly reduced to 1.5% (6/388) ( P<0.0001). Three (50%) of the six failures after pathway initiation were long examinations (>55 min). Deviation from the recommended medication protocol accounted for most of the 115 delays. Only minor adverse events were seen (12/388, 3.1%). CONCLUSION: Implementing a pediatric sedation pathway significantly decreases the sedation failure rate. Pediatric residents and nurses can safely, effectively and efficiently sedate pediatric patients for routine diagnostic imaging procedures without the need for a radiology department sedation team in a department with a small-to-moderate volume of pediatric patients.

Threshold sensitivity and frequency specificity in auditory brainstem response audiometry.

Frequency-specific electric response audiometry can be performed on difficult to test young children if the child is sedated and proper choices are made of acoustic stimuli and recording parameters, although certain compromises are necessary. A very satisfactory sedative is secobarbital, administered intramuscularly in doses related to the weight of the child. As stimuli we recommend '2-1-2' tone bursts at 500, 1 000, 2 000, and 4 000 Hz: i.e., with a rise and fall of two periods and a plateau of one period of the modulated tone. A very robust and sensitive response that is not significantly modified by the sedation and is effective for all four frequencies is the P6-SN10 of the early brainstem sequence. To record this complex favorably requires a bandpass input filter of the Butterworth type with pass-band (at -3 dB) from 50 to 1 700 Hz and rejection rates of 24 dB/octave. With this combination, polarity of stimulus is unimportant and sweep time, rate of stimulation and number of responses averaged may be selected for convenience and simplicity. A routine that requires about an hour of testing time is described and the necessary correction factors are given for estimating a child's behavioral pure-tone thresholds. We believe that our threshold estimates are generally correct within 10 dB, and are sufficiently frequency-specific for proper selection of a hearing aid.

Sedation in pediatric dentistry: a practical assessment procedure.

An assessment model for evaluating sedation in pediatric dental patients has been described. The model in whole or in part can be a valuable asset in drug trials and clinical evaluations. The unique characteristics of this model include: assessments are easily and quickly carried out without interruption of normal patient care; the criteria for sedation behavior can be standardized and are clinically relevant; a determination of the level of consciousness using an airway obstruction maneuver permits an assessment of safety; and the reliability of the observer ratings is extremely high, thereby avoiding the necessity of specially trained personnel. Using the assessment procedure, a placebo-controlled, double-blind clinical trial of various doses of chloral hydrate with and without N2O was performed. The results indicate that: children receiving the placebo treatment behaved favorably for at least 46% of the ratings; the 20 mg/kg and 40 mg/kg chloral hydrate groups showed little or no improvement when compared with the placebo group; the group receiving 60 mg/kg chloral hydrate had as much as a 33% improvement in behavior as compared with placebo; and with the addition of 40% N2O/60% O2 to 60 mg/kg chloral hydrate premedication, four of 15 children (27%) were unable to maintain a patent airway when intentionally obstructed.

A balanced oral sedation technique.

The results of the preliminary clinical investigation for treating ambulatory patients in a nonhospital environment offer the following advantages of the regimen discussed: A high degree of predictability, with a wide margin of safety, when utilized properly. All of the patient's vital signs remained stable, although respiratory rate and depth were depressed for short periods of time. Adequate working time to perform all phases of pedodontic dentistry, with a minimum amount of postoperative nausea. A smooth onset of action and a good experience of young patients who were confronted with a stressful situation. Profound local anesthesia is mandatory, otherwise painful stimuli will awaken the patient and result in a stormy encounter. The personality and experience of the dental personnel contributed a great deal to the smoothness and success of the procedure.

Experimental colonic tumours in the rat. I. Preparation and technique of examination.

A method is described for demonstrating the mucosal appearance of the colon of the rat with double contrast and magnification radiography. The rats were examined at regular intervals. Double contrast examinations were performed 1 570 times in 418 rats. The animals were prepared by cleansing the colon with enemas. The mortality rate for different forms of anesthesia was recorded. An anesthesia with intraperitoneal administration of chloralhydrate and atropine-sulfate was the most appropriate.