Formulation and assessment of hydroxyzine HCL solid lipid nanoparticles by dual emulsification technique for transdermal delivery.

Hydroxyzine HCL (HHCL) is an antihistamine, used for the treatment of allergic skin conditions. The purpose of this study was to achieve a dual phase drug delivery rate across the intact skin, to enhance HHCL permeation through the stratum corneum, to assess the peripheral H1-antihistaminic activity and the extent to which HHCL was systemically absorbed from transdermal gel loaded with solid lipid nanoparticles (SLNs), as well as to avoid its extreme bitterness. According to 23 factorial design, eight formulations of HHCL-SLNs were prepared by the double emulsification method. Lipid type (XA), surfactant concentration (XB) and co-surfactant concentration (XC) were the independent variables. All formulations were characterized for their surface morphology, particle size, entrapment efficiency and in-vitro drug release study. The optimized formula that provides greater desirability was then incorporated into the transdermal gel. In addition, the efficacy of the developed gel was tested in-vivo using 2,4-Dinitrochlorobenzene induced atopic dermatitis as lesion model in mice. F4 showed an average diameter 111 nm ± 0.03, zeta potential - 30 MV ± 2.4 and EE 75.2% ± 4.4. TEM images showed spherical, smooth morphology with uniform particles distribution. In-vivo study demonstrated potent antipruritic efficacy of transdermal gel in atopic dermatitis such as induced lesions compared to HHCL gel. Hence, HHCL solid lipid nanoparticles transdermal gel may be considered as potential for delivery of HHCL and alternatively to traditional oral use.

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

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

The histamine H1 receptor antagonist hydroxyzine enhances sevoflurane and propofol anesthesia: A quantitative EEG study.

OBJECTIVE: The aim of this study was to determine the anesthesia-promoting effects of hydroxyzine on electroencephalograms during sevoflurane anesthesia and during propofol anesthesia. METHODS: We analyzed 40 patients scheduled for elective surgery under sevoflurane anesthesia (n = 20) or propofol anesthesia (n = 20). Anesthesia was adjusted at a bispectral index value of 50-60, and then 0.5 mg/kg of hydroxyzine was administered intravenously. We analyzed frontal electroencephalograms before and after hydroxyzine injection with power spectral and bicoherence analyses, which are suitable for assessing the anesthetic depth induced by γ-aminobutyric acid (GABA)ergic anesthetics. RESULTS: Hydroxyzine increased the α bicoherence peaks in both sevoflurane anesthesia (mean difference, 11.2%; 95% confidence interval (CI), 7.6 to 14.8; P < 0.001) and propofol anesthesia (mean difference, 5.6%; 95% CI, 1.7 to 9.4; P = 0.008). Hydroxyzine increased the averaged δ bicoherence values in both sevoflurane anesthesia (mean difference, 5.5%; 95% CI, 2.1 to 8.8; P = 0.003) and propofol anesthesia (mean difference, 3.9%; 95% CI, 1.0 to 6.8; P = 0.011). CONCLUSIONS: Hydroxyzine enhances both sevoflurane anesthesia and propofol anesthesia probably by facilitation of GABAergic neural circuit mechanisms. SIGNIFICANCE: The findings provide a new insight into the role of histaminergic neurons during general anesthesia in humans.

The Role of Alcohol Dehydrogenase in Drug Metabolism: Beyond Ethanol Oxidation.

Alcohol dehydrogenases (ADHs) are most known for their roles in oxidation and elimination of ethanol. Although less known, ADHs also play a critical role in the metabolism of a number of drugs and metabolites that contain alcohol functional groups, such as abacavir (HIV/AIDS), hydroxyzine (antihistamine), and ethambutol (antituberculosis). ADHs consist of 7 gene family numbers and several genetic polymorphic forms. ADHs are cytosolic enzymes that are most abundantly found in the liver, although also present in other tissues including gastrointestinal tract and adipose. Marked species differences exist for ADHs including genes, proteins, enzymatic activity, and tissue distribution. The active site of ADHs is relatively small and cylindrical in shape. This results in somewhat narrow substrate specificity. Secondary alcohols are generally poor substrates for ADHs. In vitro-in vivo correlations for ADHs have not been established, partly due to insufficient clinical data. Fomepizole (4-methylpyrazole) is a nonspecific ADH inhibitor currently being used as an antidote for the treatment of methanol and ethylene glycol poisoning. Fomepizole also has the potential to treat intoxication of other substances of abuse by inhibiting ADHs to prevent formation of toxic metabolites. ADHs are inducible through farnesoid X receptor (FXR) and other transcription factors. Drug-drug interactions have been observed in the clinic for ADHs between ethanol and therapeutic drugs, and between fomepizole and ADH substrates. Future research in this area will provide additional insights about this class of complex, yet fascinating enzymes.

Synergistic Effects of Korean Red Ginseng Extract and the Conventional Systemic Therapeutics of Atopic Dermatitis in a Murine Model.

The synergistic effects of Korean Red ginseng (KRG, Panax ginseng C.A. Mey.) on conventional systemic therapeutics of atopic dermatitis (AD) have not been studied yet. To analyze the synergistic effects of KRG extract and the conventional systemic therapeutics of AD in TNCB-induced AD mouse model, we determined the change in modified scoring of index, the transepidermal water loss, the skin pathology, serum IgE, and the expression of various cytokines after combination treatment to the five-week-old NC/Nga female mice. The severity of AD was significantly decreased in the KRG + hydroxyzine (AH) group than AH group, and in the KRG + evening primrose oil (EPO) group than EPO group. A significant decrease in dermal inflammation was observed in the KRG + AH group than that in the AH group, and in the KRG + EPO group than that in the EPO group (p = 0.008), respectively. A decrease in CD1a expression was observed in the KRG + AH group when compared to the AH group (p = 0.008), and KRG + EPO group when compared to the EPO group. Compared to the CS group, the KRG + CS group showed a significant decrease in IL-17 expression. A combination of KRG and conventional systemic therapeutics can safely and effectively manage the AD.

Uso de corticosteroides no tratamento da lesão hepática aguda grave decorrente de anabolizante estanazolol / Use of corticosteroids in the treatment of stanazolol-induce severe acute liver injury

A busca pelo corpo perfeito pode gerar graves consequências para a população que faz uso indiscriminado de substâncias visando a resultados rápidos. O caso relatado se refere a um pa- ciente de 21 anos, do sexo masculino, na cidade de São Paulo (SP), que apresentou quadro de síndrome colestática 15 dias após uso do anabolizante estanazolol para fins estéticos na ativi- dade física, evoluindo com hepatite medicamentosa grave, com aumento de transaminases, hiperrubilinemia às custas de bilirrubina direta e fatores de coagulação, sem resposta satis- fatória ao tratamento de suporte convencional, com melhora significativa após introdução de corticoterapia.

Searching for the perfect body image can cause severe conse- quences to the population using substances indiscriminately to reach results fast. The case reported refers to a male patient, 21 years old, from the city of São Paulo (SP), who developed choles- tatic syndrome 15 days after the use of the steroid Stanazol for aesthetic purposes during physical activity, progressing with se- vere drug-induced hepatitis, transaminases, bilirubin, and coagu- lation factors increase with no satisfactory response to the con- ventional support treatment, and significant improvement after the introduction of corticotherapy.

Comparison of gabapentin and hydroxyzine in the treatment of pruritus in patients on dialysis.

BACKGROUND: Pruritus is one of the most common problems in patients with chronic renal failure. Of all patients with end-stage renal disease (ESRD), 60-80% report pruritus during their life. AIM: To compare the effect of gabapentin (GBP) and hydroxyzine (HYDZ) in treating pruritus in patients on dialysis. METHODS: In a double-blind, randomized, crossover clinical trial, 32 patients on dialysis who reported pruritus were assigned randomly to receive either GBP or HYDZ for 6 weeks; the first group received GBP 100 mg/day orally and the second group received HYDZ 25 mg/day orally for 6 weeks. After this 6-week period (Period 1) there was a washout period of 2 weeks then patients were crossed over to the other drug (the first group receiving HYDZ and second group receiving GBP) and followed up for a further 6 weeks (Period 2). A visual analogue scale was used to measure pruritus intensity in the groups before and after the first and second period. RESULTS: In Period 1, pruritus severity decreased from 7.1 ± 1.46 at baseline to 2.17 ± 1.82 at 6 weeks in the GBP group (P = 0.001) and from 6.83 ± 2.11 to 2.86 ± 1.67 in the HYDZ group (P = 0.001). In Period 2, pruritus severity decreased from 5.1 ± 1.61 at baseline to 1.56 ± 0.82 at 6 weeks in the GBP group (P < 0.01) and from 5.23 ± 2.11 to 2.1 ± 1.87 in the HYDZ group (P = 0.001). CONCLUSION: Results showed that both HYDZ and GBP significantly improved and controlled pruritus in patients on dialysis, with no significant difference observed between the two drugs.

A Case Report of Serotonin Syndrome in a Patient on Selective Serotonin Reuptake Inhibitor (SSRI) Monotherapy.

INTRODUCTION: Paroxetine is a selective serotonin reuptake inhibitor (SSRI) with several indications, one of which is for depression. We present a case of probable paroxetine-induced serotonin syndrome. CASE SUMMARY: A 21-year-old female with a history of generalized anxiety disorder and major depression presented with increased depressive symptoms over several months while taking fluoxetine 20 mg daily. Fluoxetine was discontinued without taper and replaced with paroxetine 10 mg daily, along with hydroxyzine 50 mg twice daily as needed for anxiety. Within a week of starting the paroxetine, the patient reported increased anxiety, insomnia, and constant shaking. The paroxetine continued to be uptitrated over a 3-week period to a dose 30 mg due to unremitting depressive symptoms. One month later, the patient presented with tachycardia, generalized body aches, extreme fatigue, weakness, uncontrollable twitching, tremor, and hyperreflexia. A widespread burning sensation accompanied by random hot flashes without diaphoresis was also noted. Serotonin syndrome was diagnosed using the Hunters criteria. Paroxetine was discontinued, and the patient's physical symptoms resolved within a week. DISCUSSION: To date, only 5 cases of serotonin syndrome have been reported in patients receiving SSRI monotherapy at recommended therapeutic doses.

Pharmacokinetics of hydroxyzine and cetirizine following oral administration of hydroxyzine to exercised Thoroughbred horses.

Hydroxyzine is a first-generation antihistamine and cetirizine, a second-generation antihistamine and active metabolite of hydroxyzine. Hydroxyzine is commonly used in performance horses and as such its use in closely regulated; however, there are no published studies suitable for establishing appropriate regulatory recommendations. In the current study, 12 exercised Thoroughbred research horses received a single oral administration of 500 mg of hydroxyzine. Blood and urine samples were collected prior to and up to 96 hr postdrug administration and concentrations of hydroxyzine and cetirizine determined using liquid chromatography-tandem mass spectrometry. A joint parent/metabolite population 2-compartment pharmacokinetic model with first-order absorption and elimination was utilized to describe the pharmacokinetics of both compounds. Serum hydroxyzine and cetirizine concentrations were above the limit of quantitation (0.1 ng/ml) of the assay at 96 hr (the last time point sampled). The terminal half-life was 7.41 and 7.13 hr for hydroxyzine and cetirizine, respectively. Findings from this study suggest that a prolonged withdrawal time should be observed if this compound is used in performance administered to performance horses and is classified as prohibited substance by the applicable regulatory body.

Enteral versus intravenous approach for the sedation of critically ill patients: a randomized and controlled trial.

BACKGROUND: ICU patients must be kept conscious, calm, and cooperative even during the critical phases of illness. Enteral administration of sedative drugs might avoid over sedation, and would be as adequate as intravenous administration in patients who are awake, with fewer side effects and lower costs. This study compares two sedation strategies, for early achievement and maintenance of the target light sedation. METHODS: This was a multicenter, single-blind, randomized and controlled trial carried out in 12 Italian ICUs, involving patients with expected mechanical ventilation duration > 72 h at ICU admission and predicted mortality > 12% (Simplified Acute Physiology Score II > 32 points) during the first 24 h on ICU. Patients were randomly assigned to receive intravenous (midazolam, propofol) or enteral (hydroxyzine, lorazepam, and melatonin) sedation. The primary outcome was percentage of work shifts with the patient having an observed Richmond Agitation-Sedation Scale (RASS) = target RASS ±1. Secondary outcomes were feasibility, delirium-free and coma-free days, costs of drugs, length of ICU and hospital stay, and ICU, hospital, and one-year mortality. RESULTS: There were 348 patients enrolled. There were no differences in the primary outcome: enteral 89.8% (74.1-100), intravenous 94.4% (78-100), p = 0.20. Enteral-treated patients had more protocol violations: n = 81 (46.6%) vs 7 (4.2%), p < 0.01; more self-extubations: n = 14 (8.1%) vs 4 (2.4%), p = 0.03; a lighter sedative target (RASS = 0): 93% (71-100) vs 83% (61-100), p < 0.01; and lower total drug costs: 2.39 (0.75-9.78) vs 4.15 (1.20-20.19) €/day with mechanical ventilation (p = 0.01). CONCLUSIONS: Although enteral sedation of critically ill patients is cheaper and permits a lighter sedation target, it is not superior to intravenous sedation for reaching the RASS target. TRIAL REGISTRATION: ClinicalTrials.gov, NCT01360346 . Registered on 25 March 2011.

Sedation of children undergoing dental treatment.

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

A Retrospective Study of Dosing Weight and Outcomes for One Pediatric Dental Sedation Regimen.

Purpose: The purpose of this study was to assess the use of a dosing scalar for association with the success of procedural sedation in pediatric dentistry. Methods: This cross-sectional, retrospective study assessed healthy two- to 12-year-olds who received an elixir of midazolam (0.3 mg/kg), meperidine (1.5 mg/kg), and hydroxyzine (1.0 mg/kg). The scaled body weight (SBW) for each patient was determined using the 50th percentile weight-for-age from the 2000 Centers for Disease Control and Prevention (CDC) growth chart. Children under the 50th percentile were dosed at their actual weight. Children weighing over the 50th percentile received a dose that was reduced to the 50th percentile weight-for-age. Statistical analysis evaluated sedation success, measured by the Houpt scale. Lean body weight (LBW) and ideal body weight (IBW) were calculated to compare SBW with other available dosing scalars. Results: The sample consisted of 427 children. The success was 73.8 percent. There was no significant difference in sedation success by dose delivered. The calculated LBW and IBW were significantly greater than the SBW (P<.001, P<.001). Conclusions: Sedation success was not affected by use of a scalar that reduced dosing weight to the 2000 CDC growth chart's 50th percentile weight-for-age.

Comparison of Two Morphine-Benzodiazepine-Hydroxyzine Combinations for the Oral Sedation of Pediatric Dental Patients: A Retrospective Study.

PURPOSE: To investigate the effectiveness of oral morphine sulfate regimens in sedating pediatric dental patients and assess whether pre-sedation disposition and willingness to take the sedative were related to the outcome of the sedation. METHODS: The sedation records of 271 pediatric dental patients sedated with oral morphine were reviewed. Children were either sedated with regimen one (morphine plus midazolam plus hydroxyzine) or regimen two (morphine plus diazepam plus hydroxyzine). Data gathered included the patient's pre-sedation disposition, willingness to take the sedative, effectiveness of sedation, and occurrence of any adverse event. Data analysis was conducted using descriptive statistics, Pearson's chi-square, and logistic regression. RESULTS: Regimens one and two had an overall success rate of 80 percent (143 out of 178) and 81 percent (75 out of 93), respectively. A positive correlation was observed between the patient's willingness to take his/her sedative medication and the effectiveness of the sedation using both the Pearson's chi-square (P=.004) and logistic regression (P=.028). Adverse events occurred in six percent (17 out of 271) of the cases. CONCLUSIONS: Overall rate of effective sedation using various oral morphine sulfate regimens was above 80 percent. Minimal adverse events occurred. The patient's willingness to take the sedative was positively associated with the outcome of the sedation regimen.

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.

Efficacy of the Sequential Administration of Melatonin, Hydroxyzine, and Chloral Hydrate for Recording Sleep EEGs in Children.

Sedation of children for electroencephalography (EEG) recordings is often required. Chloral hydrate (CH) requires medical clearance and continuous monitoring. To try to reduce personnel and time resources associated with CH administration, a new sedation policy was formulated. This study included all children who underwent an EEG during a consecutive 3-month period following the implementation of the new sedation policy, which consists of the sequential administration of melatonin, hydroxyzine (if needed), and CH (if needed). The comparator group included all children with a recorded EEG during a consecutive 3-month period when the sedation policy consisted of the sole administration of CH. A total of 803 children with a mean age of 7.9 years (SD = 5.1, range = 0.5-17.7 years) were included. Sleep EEG recordings were obtained in 364 of 385 children (94.6%) using the old sedation policy and in 409 of 418 children (97.9%) using the new one. With the new sedation policy, the percentage of children requiring CH dropped from 37.1% to 6.7% (P < .001). Time to sleep onset and duration of sleep were not significantly different between the 2 policies. The new sedation policy was very well tolerated. The new sedation policy is very safe, is highly efficacious in obtaining sleep EEG recordings, and will result in substantial saving of time and personnel resources.