BACKGROUND: Pharmacological methods, specifically sedatives, have gained popularity in managing the behavior of children during dental appointments.
OBJECTIVE: The aim of this study was to compare 1 m/kg intranasal dexmedetomidine, 0.3 mg/kg intranasal midazolam, and nitrous oxide in evaluating the level of sedation, behavior of the child, onset of sedation, physiologic signs, and adverse effects.
METHODS: In this cross-over trial, 15 children aged 6-8 years were randomized to receive intranasal atomized dexmedetomidine, intranasal atomized midazolam, and inhalation nitrous oxide at three separate visits. After administering the sedative agent, a single pulpectomy was performed during each appointment, and the outcomes were recorded. The washout period between each visit was 1 week.
RESULTS: All three sedative agents were equally effective in controlling overall behavior. Dexmedetomidine showed lower sedation level scores (agitated; score 9) than the other groups. There was a statistically significant difference in the onset of sedation, with dexmedetomidine having the longest onset of 36.2 ± 9.47 min. Coughing and sneezing were predominantly observed after administration of intranasal midazolam. Oxygen saturation levels were statistically lower in the intranasal midazolam group during local anesthesia administration and post-treatment.
CONCLUSIONS: 0.3 mg/kg intranasal midazolam is as effective as nitrous oxide sedation for controlling behavior and providing adequate sedation in pediatric dental patients. However, 1 m/kg dexmedetomidine did not provide the same level of sedation and had a significantly longer onset. 0.3 mg/kg intranasal midazolam is an effective alternative to nitrous oxide sedation in anxious children.

Combinations of different drugs are formulated in autoinjectors for parenteral administration against neurotoxic war agents. In this work, the effects on the chemical stability of the following three variables were studied: (i) type of drug combination (pralidoxime, atropine, and midazolam versus obidoxime, atropine, and midazolam); (ii) pH (3 versus 4); and (iii) type of elastomeric sealing material (PH 701/50 C BLACK versus 4023/50 GRAY). Syringes were stored at three different temperatures: 4, 25, and 40 °C. Samples were assayed at different time points to study the physical appearance, drug sorption on the sealing elastomeric materials, and drug content in solution. Midazolam was unstable in all tested experimental conditions. Drug adsorption was observed in both types of sealing elastomeric materials and was significantly (p < 0.01) dependent on the lipophilicity of the drug. The most stable formulation was the combination of pralidoxime and atropine at pH 4 with the elastomeric sealing material 4023/50 GRAY.

Exposure to general anesthetics can adversely affect brain development, but there is little study of sedative agents used in intensive care that act via similar pharmacologic mechanisms. Using quantitative immunohistochemistry and neurobehavioral testing and an established protocol for murine sedation, we tested the hypothesis that lengthy, repetitive exposure to midazolam, a commonly used sedative in pediatric intensive care, interferes with neuronal development and subsequent cognitive function via actions on the mechanistic target of rapamycin (mTOR) pathway. We found that mice in the midazolam sedation group exhibited a chronic, significant increase in the expression of mTOR activity pathway markers in comparison to controls. Furthermore, both neurobehavioral outcomes, deficits in Y-maze and fear-conditioning performance, and neuropathologic effects of midazolam sedation exposure, including disrupted dendritic arborization and synaptogenesis, were ameliorated via treatment with rapamycin, a pharmacologic mTOR pathway inhibitor. We conclude that prolonged, repetitive exposure to midazolam sedation interferes with the development of neural circuitry via a pathologic increase in mTOR pathway signaling during brain development that has lasting consequences for both brain structure and function.

BACKGROUND: Sedation during flexible bronchoscopy (FB) should maintain an adequate respiratory drive, ensure maximum comfort for the patient, and warrant that the objectives of the procedure are achieved. Nevertheless, the optimal sedation method for FB has yet to be established. This study aimed to compare the standard recommended combination of midazolam-fentanyl (MF) with that of dexmedetomidine-ketamine (DK) for patient sedation during FB.
METHODS: Patients subjected to FB were randomly assigned to a DK (n = 25) and an MF group (n = 25). The primary outcome was the rate of critical desaturation events (arterial oxygen saturation < 80% with nasal oxygen supply 2 L/min). Secondary outcomes included sedation depth, hemodynamic complications, adverse events, and patient and bronchoscopist satisfaction.
RESULTS: The incidence rates of critical desaturation events were similar between the two groups (DK: 12% vs. MF: 28%, p = 0.289). DK achieved deeper maximum sedation levels (higher Ramsay - lower Riker scale; p < 0.001) and was associated with longer recovery times (p < 0.001). Both groups had comparable rates of hemodynamic and other complications. Patient satisfaction was similar between the two groups, but bronchoscopist satisfaction was higher with the DK combination (p = 0.033).
CONCLUSIONS: DK demonstrated a good safety profile in patients subjected to FB and achieved more profound sedation and better bronchoscopist satisfaction than the standard MF combination without increasing the rate of adverse events.

BACKGROUND: Dexmedetomidine and midazolam are commonly used sedatives in children. We conducted a systematic review and meta-analysis to compare the safety and effectiveness of sedation provided by dexmedetomidine combined with midazolam versus other sedatives including chloral hydrate, midazolam and other sedatives in pediatric sedation.
METHODS: The Embase, Web of Science, Cochrane Library, and PubMed databases, and Clinicaltrials.gov register of controlled trials were searched from inception to June 2022. All randomized controlled trials used dexmedetomidine-midazolam in pediatric sedation were enrolled. The articles search, data extraction, and quality assessment of included studies were performed independently by two researchers. The success rate of sedation was considered as the primary outcome. The secondary outcomes included onset time of sedation, recovery time of sedation and occurrence of adverse events.
RESULTS: A total of 522 studies were screened and 6 RCTs were identified; 859 patients were analyzed. The administration of dexmedetomidine combined with midazolam was associated with a higher sedation success rate and a lower incidence of nausea and vomiting in computed tomography, magnetic resonance imaging, Auditory Brainstem Response test or fiberoptic bronchoscopy examinations than the other sedatives did (OR = 2.92; 95% CI: 1.39-6.13, P = 0.005, I2 = 51%; OR = 0.23, 95% CI: 0.07-0.68, P = 0.008, I2 = 0%, respectively). Two groups did not differ significantly in recovery time and the occurrence of adverse reactions (WMD = - 0.27, 95% CI: - 0.93 to - 0.39, P = 0.42; OR 0.70; 95% CI: 0.48-1.02, P = 0.06, I2 = 45%. respectively). However, the results of the subgroup analysis of ASA I-II children showed a quicker onset time in dexmedetomidine-midazolam group than the other sedatives (WMD=-3.08; 95% CI: -4.66 to - 1.49, P = 0.0001, I2 = 30%).
CONCLUSIONS: This meta-analysis showed that compared with the control group, dexmedetomidine combined with midazolam group provided higher sedation success rates and caused a lower incidence of nausea and vomiting in completing examinations, indicating a prospective outpatient clinical application for procedural sedation.

OBJECTIVE: Was to improve the quality of treatment in pediatric outpatient dentistry with the effective use of oral sedation.
METHODS: The study comprised 60 children aged 3-12 years who were undergoing therapeutic/surgical dental treatment. All children\'s somatic state was assessed as ASAI-II. All children met a number of psychological, anamnestic and procedural criteria. Midazolam and chloropyramine in a dose calculated for the patient\'s body weight were used as components of oral sedation. The estimated sedation depth was Ramsay II-III. The study included an analysis of objective (the time of comfortable treatment, the amount of treated or removed teeth per visit, the possibility of treatment without anesthesia during further visits) and subjective (the possibility of contact with the child during treatment, behavioral reactions at home and on further visits) criteria. Negative behavioral reactions and dental effects were also assessed.
RESULTS: The treatment features correlated with the age category and gender of the patient. In the older age group of 7-12 years, the amount of comfortable treatment time was higher, the possibility of contact with the child reached 100% (which is twice as much as in the younger one), and also a larger number of patients were treated during further visits without an anesthetic aid. At the same time, in the younger age group of 3-6 years, the volume of treatment per visit was higher, since it takes less time to treat a primary tooth than for a permanent one. Side effects (visual hallucinations, diplopia, hyperactivity, tearfulness and aggressiveness) were more often recorded in the younger age group, but emotional instability was equally manifested in both groups.
CONCLUSIONS: In order to maximize the effectiveness of using oral sedation as a method, it is necessary to take into account the duration and traumatism of the proposed procedure, the peculiarities of age psychology and the peculiarities of the psychological development of boys and girls.
UNASSIGNED: Улучшить качество лечения детей в амбулаторной стоматологии путем эффективного применения пероральной седации.
UNASSIGNED: В исследование вошли 60 детей в возрасте 3—12 лет, которым предстояло терапевтическое/хирургическое стоматологическое вмешательство. Все дети соответствовали по соматическому состоянию ASA I—II и отвечали ряду психологических, анамнестических и процедуральных критериев. В качестве компонентов пероральной седации использовались препараты мидазолам и хлоропирамин в дозе, рассчитанной на массу тела пациента. Предполагаемая глубина седации — Ramsay II—III. Анализировались объективные критерии: время комфортного лечения, объем лечения за один визит, возможность лечения без анестезиологического пособия при дальнейших визитах; а также субъективные: возможность контакта с ребенком в процессе лечения, поведенческие реакции в домашних условиях и на дальнейших визитах. Также оценивались негативные поведенческие реакции и стоматологические эффекты.
UNASSIGNED: Особенности лечения коррелировали с возрастной категорией и полом пациента. В старшей возрастной категории 7—12 лет была больше величина комфортного времени лечения, возможность контакта с ребенком достигла 100% (что в два раза больше, чем в младшей), а также большее количество пациентов было пролечено при дальнейших визитах без анестезиологического пособия. При этом в младшей возрастной категории 3—6 лет был больше объем лечения за один визит, так как для лечения одного временного зуба необходимо меньше времени, чем для постоянного. Побочные эффекты (зрительные галлюцинации, диплопия, гиперактивность, плаксивость и агрессивность) чаще регистрировались в младшей возрастной категории, однако эмоциональная нестабильность была равно проявлена в обеих группах.
UNASSIGNED: Для наибольшей эффективности использования пероральной седации необходимо учитывать длительность и травматичность предполагаемой процедуры, особенности возрастной психологии и особенности психологического развития мальчиков и девочек.

UNASSIGNED: Penile plication is commonly performed for Peyronie\'s disease under general or spinal anesthesia. Conscious sedation (CS) offers decreased anesthetic risks, cost-effectiveness, and the ability to perform the procedure in outpatient settings with shorter wait times. We sought to compare tolerability of penile plication under deep intravenous sedation (DIS) administered by anesthesiologists and nursing-administered CS (NACS).
UNASSIGNED: Tolerability for penile plication was prospectively evaluated, excluding revision surgeries and those with hourglass or hinge deformities. DIS included midazolam and ketamine with infusion of propofol and remifentanil. NACS consisted of midazolam and fentanyl. Baseline characteristics, procedural information, and patient- and surgeon-reported pain assessments were collected. Patients were administered a standardized tolerability questionnaire on follow-up.
UNASSIGNED: Forty patients were enrolled (23 DIS; 17 NACS) with similar baseline characteristics. Median curvature of the DIS cohort was 55° (interquartile range = 43.75-76.25) and 45° (interquartile range = 45-60) in NACS. There was a 100% success rate with no procedure abortion or conversion to general anesthetic. On follow-up, all patients had functional curvature (<20°), and 100% of patients in the DIS and NACS cohorts reported that they would recommend CS to others. Over 93% of patients in both cohorts would choose CS over general anesthetic in the future, with no differences in perioperative and postoperative pain between groups.
UNASSIGNED: Penile plication with CS, whether administered by an anesthesiologist or nursing, is well tolerated with no differences in pain or complications. This indicates that outpatient penile plication with trained nursing staff administering CS can safely reduce costs, risks, and wait times.

UNASSIGNED: The effectiveness and safety of propofol-based sedation and midazolam sedation in pediatric bidirectional endoscopy were compared.
UNASSIGNED: We retrospectively analyzed the cases of pediatric patients (≤15 years old) who had undergone bidirectional endoscopy, esophagogastroduodenoscopy, and colonoscopy by pediatric gastroenterologists. Demographic data, indications, sedatives/dosages, clinical outcomes, endoscopic findings, adverse events, and total patient time requirements (total time in which patients stay in our hospital) were compared in the two sedation groups.
UNASSIGNED: Ninety-one children (51 boys, 40 girls, mean age 13 years, range 9-15) treated at our hospital were enrolled. Propofol alone or in combination with midazolam and/or pentazocine was administered to 51 patients (propofol-based sedation group). Midazolam alone or in combination with pentazocine was administered to the other 40 patients (midazolam sedation group). In the propofol group, the following mean doses were used: propofol, 96 mg (range 40-145 mg); midazolam, 4.9 mg (range 3-5 mg); and pentazocine, 7.5 mg. In the midazolam group, the mean doses of midazolam and pentazocine were 6.2 mg (range 4-10 mg) and 15 mg, respectively. All procedures were successfully completed by pediatric gastroenterologists. The total procedure times and endoscopic findings were similar in the two groups, but the median patient time requirement in the propofol group was significantly shorter versus the midazolam group (7.3 h vs. 8.4 h, p < 0.001). No adverse events occurred in either group.
UNASSIGNED: Propofol-based sedation in pediatric bidirectional endoscopy was safely and effectively performed by pediatric gastroenterologists, and its patient time requirement was shorter than that for midazolam sedation.

UNASSIGNED: Standard dosages of analgesic and sedative drugs are given to intensive care patients. The resulting range of blood concentrations and corresponding clinical responses need to be better examined. The purpose of this study was to describe daily dosages, measured blood concentrations, and clinical responses in critically ill patients. The purpose was also to contribute to establishing whole blood concentration reference values of the drugs investigated.
UNASSIGNED: A descriptive study of prospectively collected data from 302 admissions to a general intensive care unit (ICU) at a university hospital. Ten drugs (clonidine, fentanyl, morphine, dexmedetomidine, ketamine, ketobemidone, midazolam, paracetamol, propofol, and thiopental) were investigated, and daily dosages recorded. Blood samples were collected twice daily, and drug concentrations were measured. Clinical responses were registered using Richmond agitation-sedation scale (RASS) and Numeric rating scale (NRS).
UNASSIGNED: Drug dosages were within recommended dose ranges. Blood concentrations for all 10 drugs showed a wide variation within the cohort, but only 3% were above therapeutic interval where clonidine (57 of 122) and midazolam (38 of 122) dominated. RASS and NRS were not correlated to drug concentrations.
UNASSIGNED: Using recommended dose intervals for analgesic and sedative drugs in the ICU setting combined with regular monitoring of clinical responses such as RASS and NRS leads to 97% of concentrations being below the upper limit in the therapeutic interval. This study contributes to whole blood drug concentration reference values regarding these 10 drugs.

BACKGROUND: In this study, we compare the effects of ketamine and the combination of midazolam and morphine on the severity of depression and anxiety in mechanically ventilated patients after discharge from the intensive care unit (ICU).
METHODS: This randomized single-blind clinical trial included 50 patients who were candidates for craniotomy and postoperative mechanical ventilation in the ICU of 5 Azar Teaching Hospital in Gorgan City, North Iran, from 2021 to 2022. Patients were allocated to two groups by quadruple block randomization. In group A, 0.5 mg/kg of ketamine was infused over 15 minutes after craniotomy and then continued at a dose of 5 µ/kg/min during mechanical ventilation. In group B, midazolam was infused at a dose of 2-3 mg/hr and morphine at a dose of 3-5 mg/hr. After patients were discharged from the ICU, if their Glasgow Coma Scale scores were ≥14, Beck\'s anxiety and depression inventories were completed by a psychologist within 2 weeks, 2 months, and 6 months after discharge.
RESULTS: The mean scores of depression at 2 months (P=0.01) and 6 months (P=0.03) after discharge were significantly lower in the ketamine group than in the midazolam and morphine group. The mean anxiety scores were significantly lower in the ketamine group 2 weeks (P=0.006) and 6 months (P=0.002) after discharge.
CONCLUSIONS: Ketamine is an effective drug for preventing and treating anxiety and depression over the long term in patients discharged from the ICU. However, further larger volume studies are required to validate these results.