Efficacy and Safety of Oral Midazolam Sedation Compared with its Combination with Hydroxyzine Use in Pediatric Dentistry: A Systematic Review

ABSTRACT Objective: To assess the efficacy and safety of the use of midazolam as monotherapy, compared to the associated use of midazolam and hydroxyzine for minimum and moderate sedation of children in dental offices, using data obtained from clinical trials. Material and Methods: A systematic review protocol was developed and registered on PROSPERO (CR42020208633). An electronic search was carried out in Pubmed, Lilacs, Science Direct, Open Gray, Web of Science, and central Cochrane Library. No language restrictions were included. Clinical trials were carried out with children aged 0-12 years, using midazolam as monotherapy compared to the use of midazolam associated with hydroxyzine to verify the effectiveness and safety of oral sedation. The quality of the studies was individually assessed and grouped using the RoB 2 (Revised Cochrane risk-of-bias tool for randomized trials) and GRADE (Grading of Recommendations Assessment, Development and Evaluation) systems, respectively. Results: A total of 749 studies were found. After analyzing the inclusion and removal of duplicates, two studies were analyzed for the quality of evidence. Through this analysis, it was possible to verify the very low level of scientific evidence on the superiority of the efficacy and safety of the combined use of midazolam and hydroxyzine for oral sedation in children in dental offices. Conclusion: The conflicting results and limitations of the studies enabled to establish that there is insufficient evidence to support the use of these drugs combined. There is only evidence for the use of midazolam as monotherapy.

A descrição matemática da análise eletroquímica do fármaco hidroxizina em soluções ácidas sobre um ácido sulfônico, baseado num polímero condutor / The mathematical description for the electrochemical analysis of hydroxyzine drug in acid solution over a conducting-polymer based sulfonic acid

RESUMO Um caso interessante da aplicação dos polímeros condutores funcionalizados na análise do fármaco hidroxizina em soluções ácidas vem sendo descrito do ponto de vista teórico. Um modelo matemático, correspondente ao caso, é desenvolvido e analisado mediante a teoria de estabilidade linear e da análise de bifurcações. Foi detectado que o uso de um polímero condutor de natureza ácida no processo pode deixar o uso das soluções menos ácidas do fármaco sem prejuízo para a eficiência eletroanalítica. Outrossim, foi avaliada a influência para o processo do comportamento dos grupos amina. A possibilidade das instabilidades oscilatória e monotônica também foi verificada.

SUMMARY An interesting case of the application of the functionalized conducting polymer in the analysis of hydroxyzine drug in acid solutions is described from the theoretical point of view. A mathematical model, correspondent to the case, is developed and analyzed by means of linear stability theory and bifurcation analysis. It was detected that the use of an acid conducting polymer may permit the use of less acid solution without mischief of the electroanalytical efficiency. Moreover, the influence of the aminogroups' behavior to the process was also evaluated. The possibility of the oscillatory and monotonic instabilities has also been verified.

Levofloxacin Reverses Hydroxyzine Induced Psychomotor Performance Deterioration: A Randomized Crossover Study.

Background: Levofloxacin is a third generation fluoroquinolone chemotherapeutic agent used in the treatment of severe and resistant bacterial infections; it exerts antibacterial effects in both blood and inflamed tissues. Levofloxacin leads to central nervous system stimulation via inhibition of GABA-A receptor complex like beta-lactam antibiotics. Hydoxyzineis used for the treatment of insomnia, allergic reactions and for preoperative sedation because of blocking H-1 receptors and so blocking histaminergic signals. Objectives: The aim of the present study is to elucidate the exciting effect of levofloxacin in hydroxyzine induced psychomotor performance deterioration in normal healthy volunteers. Methods: Thirty healthy medical student volunteers, aged between 22-25 years were allocating arbitrarily. All participants were habituated with the study measures and skilled on the Leeds psychomotor tester before and after levofloxacin (500 mg/day) alone or with hydroxyzine (10 mg/day). Results: Hydroxyzine impaired psychomotor performance and cognitive function, it prolongs the total reaction time, movement reaction time, recognition reaction time and distort critical flicker and fusion frequency significantly p<0.05. While levofloxacin activates psychomotor performance and cognitive function, it shortens the total reaction time, movement reaction time, recognition reaction time and regulate critical flicker and fusion frequency significantly p<0.05. The combined effect of levofloxacin and hydroxyzine produced insignificant effects on psychomotor performance and cognitive function p>0.05. Conclusion: Levofloxacin significantly improves psychomotor performance in normal, healthy volunteers and produced CNS stimulation that is able to reverse deteriorations in psychomotor performance and cognitive function induced by hydroxyzine.

Preparation and Evaluation of Modified Proniosomal Gel for Localised Urticaria and Optimisation by Statistical Method.

The objective of the study was to formulate a modified proniosomal gel (HMPG) of hydroxyzine hydrochloride. HMPG formulations were prepared by coacervation phase separation technique with different combination of non-ionic surfactants (Tweens and Spans) with phospholipids such as phospholipon 80H and 90H. Taguchi design of experiments was used to optimize the various formulation variables. The optimized HMPG formulations were evaluated for entrapment efficiency, vesicle size, SEM, FTIR, in vitro diffusion study, exvivo permeation, skin deposition, skin irritation and stability studies. Tween 60: Span 40 with Phospholipon 90 H formulation (H90-5) showed the highest entrapment efficiency of 94.8%. In vitro drug release was found to be as low as 1.33%, exvivo drug permeation into the skin showed only 1.18 % and drug deposition in the SC was found to be 88.24% at the end of 24 hr. The H90-5 formulation was found to be stable for three months at refrigeration temperature. The results revealed that modified proniosomal formulations of hydroxyzine hydrochloride were suitable for topical drug delivery system for the treatment of localized urticaria.

Co-Administration of Subeffective Anxiolytic Doses of Diazepam and Hydroxyzine in Elevated Zero-Maze in Mice

OBJECTIVE: Benzodiazepines are from the most common drugs which are used for treatment of anxiety disorders. There are other drugs with antianxiety properties including antihistamines such as hydroxyzine, too. Body of evidence show that co-administration of two drugs which act through different mechanisms, makes the dose of each drug to be reduced, while preserving the desired effect with less adverse drug reactions. The aim of this study was to see whether co-administration of subeffective antianxiety doses of diazepam and hydroxyzine has any antianxiety effect in elevated zero-maze (EZM) in mice. METHODS: To find the highest subeffective dose of each drug, different doses of hydroxyzine from 1.5 to 24 mg/kg and diazepam in doses of 0.25, 0.5 and 1 mg/kg were injected to male mice. Thirty minutes later, the animals were placed on EZM and various parameters of anxiety were recorded by a camera to assess later. After determination of subeffective antianxiety dose of the drugs, co-administration of hydroxyzine and diazepam was done and the anxiety parameters were measured. RESULTS: In co-administration of 0.25 mg/kg of diazepam and 12 mg/kg hydroxyzine, as subeffective antianxiety doses of either drug, there were not any significant differences in main anxiety parameters, i.e., time spent in open areas and open area entries compared to control group. Hence, no anxiolytic effect was seen. CONCLUSION: It seems that subeffective doses of diazepam and hydroxyzine may not have any facilitating or synergistic effect on each other in antianxiety responses in mice.

A randomized double-blinded trial of chloral hydrate with or without hydroxyzine versus placebo for pediatric dental sedation

Chloral hydrate and hydroxyzine are a drug combination frequently used by practitioners to sedate pediatric dental patients, but their effectiveness has not been compared to a negative control group in humans. The aim of this crossover, double-blinded study was to evaluate the effect of these drugs compared to a placebo, administered to young children for dental treatment. Thirty-five dental sedation sessions were carried out on 12 uncooperative ASA I children aged less than 5 years old. In each session patients were randomly assigned to groups P (placebo), CH (chloral hydrate 75 mg/kg) and CHH (chloral hydrate 50 mg/kg plus hydroxyzine 2.0 mg/kg). Vital signs and behavioral variables were evaluated every 15 min. Comparisons were statistically analyzed using Friedman and Wilcoxon tests. P, CH and CHH had no differences concerning vital signs, except for breathing rate. All vital signs were in the normal range. CH and CHH promoted more sleep in the first 30 min of treatment. Overall behavior was better in CH and CHH than in P. CH, CHH and P were effective in 62.5 percent, 61.5 percent and 11.1 percent of the cases, respectively. Chloral hydrate was safe and relatively effective, causing more satisfactory behavioral and physiological outcomes than a placebo.

A associação hidrato de cloral- hidroxizina tem sido utilizada na clínica odontológica para sedar crianças, mas sua efetividade ainda não foi comparada a um controle negativo em humanos. O objetivo deste estudo prospectivo foi avaliar o efeito dessas drogas, comparadas a um placebo, em crianças submetidas a tratamento odontológico. Trinta e cinco sessões de sedação foram realizadas em 12 crianças menores de 5 anos, não cooperativas, ASA classe I. Em cada sessão os pacientes foram aleatoriamente alocados para os grupos P (placebo), CH (hidrato de cloral 75 mg/kg) e CHH (hidrato de cloral 50 mg/kg mais hidroxizina 2,0 mg/kg). Sinais vitais e comportamento foram avaliados a cada 15 min, e comparados pelos testes de Friedman e Wilcoxon. Os grupos não apresentaram diferenças quanto às variáveis fisiológicas, exceto a freqüência respiratória. Todos sinais vitais registrados estiveram dentro de faixa aceitável. CH e CHH promoveram mais sono nos primeiros 30 min de tratamento. O comportamento geral foi melhor em CH e CHH do que em P. CH, CHH e P foram efetivos em 62,5 por cento, 61,5 por cento e 11,1 por cento dos casos, respectivamente. O hidrato de cloral foi seguro e relativamente efetivo, levando a resultados fisiológicos e comportamentais melhores que o placebo.

Safety and efficacy of hydroxyzine hydrochloride: a retrospective study / Segurança e eficácia do cloridrato de hidroxizina: um estudo retrospectivo

A retrospective case study was performed using the clinical charts of patients diagnosed with atopic dermatitis, dermatitis, urticaria, and other allergic conditions, treated with hydroxyzine hydrochloride from the period of 2001 to 2003. Patients of both sexes were identified by the diagnosis and treatment prescribed, and having returned for at least one post-treatment visit. A total of 41 patients were identified who fulfilled the criteria for this safety and efficacy analysis of hydroxyzine hydrochloride. The results suggest that hydroxyzine is an effective antihistaminic agent in the treatment of numerous allergic and inflammatory conditions.

Clinical efficacy of hydroxyzine hydrochloride in combination with haloperidol in the management of nausea induced by continuous infusion of opioids

<b>Purpose</b>: Nausea is a common distressing symptom experienced by advanced cancer patients. This study compared the clinical efficacy of haloperidol to hydroxyzine hydrochloride in combination with haloperidol in the management of nausea induced by continuous infusion of opioids. <b>Methods</b>: This retrospective study comprised 50 advanced cancer patients using continuous infusion of opioids who had been administered either haloperidol alone (haloperidol group) or hydroxyzine hydrochloride with haloperidol (hydroxyzine hydrochloride group); their nausea and characteristics were assessed using multivariate analysis. <b>Results</b>: After the continuous infusion of opioids, nausea occurred in 34% patients in the haloperidol group and 10% patients in the hydroxyzine hydrochloride group. No significant differences were observed in patient characteristics, except for the number of the patients using infusion of opioids. By multivariate analysis, nausea before using continuous infusion of opioids, ileus, and haloperidol without hydroxyzine hydrochloride were extracted as the risk factors of nausea. In both the groups, nausea occurred only in the patients using morphine; nausea occurred in 32.5% patients in the haloperidol group and in 4.5% patients in the hydroxyzine hydrochloride group. <b>Conclusion</b>: Hydroxyzine hydrochloride in combination with haloperidol was observed to be more effective than haloperidol alone in the management of nausea induced by continuous infusion of opioids.

Effects of anti-allergic drugs on intestinal mastocytosis and worm expulsion of rats infected with Neodiplostomum seoulense

The effects of anti-allergic drugs on intestinal mastocytosis and the expulsion of Neodiplostomum seoulense were observed in Sprague-Dawley rats, after oral infection with 500 metacercariae. The drugs used were hydroxyzine (a histamine receptor H1 blocker), cimetidine (a H2 blocker), cyclosporin-A (a helper T-cell suppressant), and prednisolone (a T- and B-cell suppressant). Infected, but untreated controls, and uninfected controls, were prepared. Worm recovery rate and intestinal mastocytosis were measured on weeks 1, 2, 3, 5, and 7 post-infection. Compared with the infected controls, worm expulsion was significantly (P < 0.05) delayed in hydroxyzine- and cimetidine-treated rats, despite mastocytosis being equally marked in the duodenum of all three groups. In the cyclosporin-A- and prednisolone-treated groups, mastocytosis was suppressed, but worm expulsion was only slightly delayed, without statistical significance. Our results suggest that binding of histamine to its receptors on intestinal smooth muscles is more important in terms of the expulsion of N. seoulense from rats than the levels of histamine alone, or mastocytosis.

A Multi-center Randomized Double-blind Comparative Clinical Trial of Levocetirizine and Cetirizine for the Treatment of Chronic Idiopathetic Urticaria / 中华皮肤科杂志

Objective To investigate and compare the effect and safety of levocetirizine and cetirizine for the treatment of chronic idiopathetic urticaria (CIU). Methods A multi-center, randomized and double-blind comparative clinical trial was employed. The patients with CIU were divided into levocetirizine group and cetirizine group. Levocetirizine (5mg/day) or cetirizine (10mg/day) were taken once daily for 28 days, and were followed up on the 7th day, 14th day and 28th day after starting treatment. Results One hundred and thirty cases were evaluable for the effect and safety at the end of the study. The effective rates in levocetirizine group and in cetirizine group were 73.44% and 77.27% on the 7th day after treatment, 82.81% and 81.82% on the 14th day, and 89.06% and 81.82% at the end of the therapy respectively. There was no significant difference between the two groups. The drug adverse reaction for levocetirizine group and cetirizine group were 14.06% and 18.18% respectively, which include mouth dryness, dizziness etc. Conclusion Levocetirizine is an effective and safe agent for the treatment of CIU.