Onset Of Sedation Research Articles

A comparative study of detomidine delivery via intranasal or intramuscular routes in calves undergoing disbudding

ObjectiveTo compare the sedative and physiological effects of intranasal (IN) and intramuscular (IM) delivery of detomidine in calves. Study designProspective, randomized experimental study. AnimalsA total of 20 healthy calves, aged 15.6 ± 4.2 days old, with body masses ranging from 40 to 60 kg. MethodsCalves were randomly assigned to be given detomidine (0.03 mg kg−1) by either IN or IM routes. The onset of sedation, duration of sedation and sedation score (SS) were recorded. Heart rate (HR), peripheral arterial hemoglobin oxygen saturation (SpO2), noninvasive systolic and diastolic arterial pressures (SAP and DAP, respectively), respiratory rate (fR), and rectal temperature (RT) were measured immediately before drug delivery (baseline), at 10 (T10), 15 (T15), 20 (T20), and 30 (T30) minutes after drug delivery. Calves underwent disbudding at T25. Comparisons between treatments for physiological variables were performed with an independent t test. Duration of sedation and SS were assessed with a Mann-Whitney test. ResultsOnset of sedation was 6.8 ± 2.3 (mean ± SD) and 14.1 ± 6.6 minutes in treatments IM and IN, respectively (p = 0.005). Duration of sedation was 32.5 (26–65) [median (range)] and 33 (26–52) minutes in treatments IM and IN, respectively (p = 0.622). SS was significantly higher in the IM group than the IN group at T15 (p = 0.015) and T20 (p = 0.039). HR was significantly higher with IN than IM at T20 (p = 0.022). RT was significantly lower in IN than IM at T30 (p = 0.020). fR, SpO2, SAP, and DAP did not differ significantly between treatments. Conclusions and clinical relevanceIN delivery of detomidine resulted in a slower onset of sedation compared to IM injection, although the duration of sedation did not differ between the two treatments.

Efficacy of Rectal Versus Oral Chloral Hydrate in Pediatric Auditory Brainstem Response: Randomized Controlled Trial.

To compare sedation success rates between rectal (RCH) and oral chloral hydrate (OCH) administration in children undergoing auditory brainstem response (ABR) testing and assess the incidence of adverse effects. Randomized controlled trial, performed between May 2023 and August 2023. Ear, Nose, and Throat Outpatient Department at tertiary care hospital. Pediatric patients aged 1 to 5 years, who were indicated for ABR testing were enrolled and randomly divided into 2 groups. The control group received 10% wt/vol chloral hydrate orally at a dose of 50 mg/kg, while the other group received the same dose through rectal administration. Onset of sedation, duration of sedation, recovery time, vital signs, and adverse effects were recorded and analyzed to assess sedative effectiveness and safety. Eighty-eight children were randomly assigned to RCH or OCH administration groups, the sedation success rates of RCH and OCH groups were 84.09% and 90.91%, respectively (P = .33). Adverse effects were detected in 11 children (12.5%), with a vomiting rate of 20.45% in the oral group versus 0% in the rectal group (P = .002). The diarrhea rate was 4.55% in the rectal group versus 0% in the oral group (P = .16). In either group, no serious adverse effects were documented. RCH and OCH are both safe and effective for short-term sedation in pediatric patients during ABR testing. Interestingly, RCH administration offers a high success rate without vomiting or major adverse effects. This study established the effectiveness of RCH for sedation in children under specialized supervision.

Intranasal esketamine versus esketamine-dexmedetomidine combination for premedication in pediatric patients undergoing strabismus surgery: a randomized controlled trial.

Preoperative fear and anxiety are prevalent in children undergoing surgery. The combination of esketamine and dexmedetomidine has been proposed as a promising premedication for enhancing preoperative sedation and analgesia. This study compared the premedication efficacy of intranasal esketamine alone and esketamine-dexmedetomidine combination in pediatric patients undergoing strabismus surgery. One hundred and eighty preschool children aged 2-6 years scheduled for strabismus surgery were enrolled and randomly assigned to one of the three groups: intranasal premedication with esketamine 2 mg/kg (Group K), esketamine 1 mg/kg and dexmedetomidine 1 µg/kg (Group KD1), or esketamine 0.5 mg/kg and dexmedetomidine 2 µg/kg (Group KD2). The primary outcome was the level of sedation following the intervention, as measured by the modified Yale preoperative anxiety scale (mYPAS) and sedation scale (SS). Secondary outcomes included onset time of sedation, the successful rate of peripheral intravenous cannulation, parental separation anxiety scale (PSAS), mask acceptance scale (MAS), wake-up time, duration of stay in the post-anesthesia care unit (PACU), and premedication-related adverse effects. After premedication, the mYPAS score gradually decreased in the three groups, with lower values in Group K than in Group KD1 and Group KD2 patients in 1, 5, and 10 min. SS in Group KD1 and Group KD2 steadily increased until 40 min after premedication, while SS in Group K increased in the first 5 min after premedication and maintained consistent levels during the remaining time. Sedation onset was substantially faster in Group K patients (11.4±7.8 min) than Group KD1 (18.1±7.5 min, P=0.006) and Group KD2 (18.4±6.8 min, P<0.001). PSAS, separation status, the successful rate of peripheral intravenous cannulation, and MAS were comparable among groups. There was no significant difference in terms of emergence time or duration of stay in the PACU among groups. More gastrointestinal events were observed in Group K (P<0.001). Intranasal premedication with 2 mg/kg esketamine produced a more rapid onset of sedation accompanied by more gastrointestinal reactions compared with a combination of esketamine and dexmedetomidine. ClinicalTrials.gov identifier: NCT04757675.

Pharmacological Insights and Clinical Applications of Ciprofol: A Narrative Review.

Ciprofol (HSK3486) is a novel intravenous anaesthetic developed as an alternative to propofol, offering a safer and more effective option in anaesthesia. It works primarily by modulating the gamma-aminobutyric acid (GABA) receptors in the central nervous system, leading to sedation and hypnosis. Ciprofol's unique pharmacological properties include a rapid onset of action, shorter duration, and reduced cardiovascular and respiratory depression compared to propofol, making it particularly suitable for outpatient and day surgery procedures.Molecular changes in ciprofol appear to be superior to those of other cibenzolines; it is more potent and has a stable hemodynamic effect. It has been used in primary surgery, inpatients and outpatients, and even for sedation of intensive care patients. The reported clinical data indicate that ciprofol is a powerful sedative that is characterised by a high-enough speed of emergence from the state of anaesthesia, which is necessary for outpatient conditions and intensive operating modes. It can be considered a new and important perspective in the technology of intravenous anaesthetics with its improved pharmacological characteristics and clinical effects. With the further accumulation of clinical data, ciprofol will undeniably become an essential agent in today's anaesthetic practice and contribute to an enhancement of healthcare efficiency by providing a more secure approach to numerous kinds of surgical interventions. The purpose of the current study is to provide a review of the pharmacology and clinical use of ciprofol, a new intravenous anaesthetic agent. Various studies demonstrate the functionality and safety profile of ciprofol, which solidifies it as a potential contender for propofol. Regarding respiratory depression, hypoxemia, and injection pain during hysteroscopy, ciprofol was shown to be a relatively safer option than propofol. Ciprofol can, therefore, be recommended for intravenous anaesthesia because of its effectiveness and safety, which has been clearly demonstrated. Randomised trials uniformly report the ability to achieve quicker onset of sedation and lower risk with the agent compared to propofol. These findings imply that ciprofol has many benefits concerning a variety of applications in patients due to a lower rate of adverse reactions and increased patient comfort.

Intranasal atomized dexmedetomidine alone or in combination with ketamine or midazolam to sedate healthy dogs

A prospective, randomized, blinded experiment was conducted to compare the effects of intranasal (IN) dexmedetomidine (Dex, 10 µg/kg; n=12) alone or combined with midazolam (DexM, 0.3 mg/kg; n=12) or ketamine (DexK, 2 mg/kg; n=12) in healthy dogs. Ease of administration (EA1), total administration time (TAT), time for first (TA1) and second nostril administration (TA2), and adverse events during atomization were recorded. Two days later, EA2 was assessed by IN atomization of injectable water as an additional outcome variable. Onset of sedation was evaluated, along with behavioral scores and physiological parameters from T0 (baseline) to T120. Statistical analyses included Chi-square, one-way ANOVA or Kruskal-Wallis, repeated measures or Friedman’s ANOVA, and Wilcoxon’s tests. Significance was p≤0.05.Onset of sedation was 12.9 ± 4.1, 18.2 ± 7.5, and 9.9 ± 4.3 mins (mean ± SD) for Dex, DexM, and DexK, respectively. Onset was shorter in DexK compared to DexM (p=0.002), explaining the lower behavioral scores in DexM at T15. All dogs in Dex and DexK reached adequate sedation, with peak sedation occurring at T30, while some dogs in DexM never reached adequate sedation and this group peaked at T45. Adverse events such as saliva drooling and pawing at the nose were significantly higher in DexM and DexK, explaining their differences in TA2, TAT, and EA1 comparing to Dex. EA2 was also higher in Dex compared to DexM and DexK. In conclusion, Dex was better tolerated in dogs and DexK showed faster and more profound sedative effects. Due to paradoxical excitement, unpredictable sedation, and nasal irritation, DexM is not recommended.

Paravertebral block with lignocaine-bupivacaine mixture in goats

Loco-regional anaesthesia and sedation protocols are becoming more popular in ruminant. This research compared some effects of xylazine or acepromazine in combination with lignocaine-bupivacaine mixture for paravertebral nerve block in goats. Twenty adult, apparently healthy West African Dwarf goats were randomly allocated to two groups (five males and five females each). Each group received either xylazine (0.05 mg/kg) + 2 % lignocaine (2mg/kg) – 0.5 % bupivacaine (0.95 mg/kg) mixture (XLB) or acepromazine (0.05 mg/kg) + lignocaine-bupivacaine mixture (ALB). Clinical parameters were recorded immediately (0 minutes) and at 10-minute intervals for an hour and 24 hours. Venipuncture was carried out via jugular vein for haematology before administration of drug (B0), 30 minutes (B30), 60 minutes (B60) and 24 hours (B24). Data was analyzed using descriptive statistics and presented as mean and standard deviation at a significance level of 0.05. The onset of deep sedation following administration of acepromazine was 31.5 ± 0.97, while it was 2.90 ± 0.57 for xylazine. Acepromazine significantly (P &lt; 0.05) reduced the rectal temperatures (RT) of the goats within the first 20 minutes and significantly reduced the respiratory rates of the goats when compared to xylazine. None of the drugs significantly altered the heart rate of the goats. None of the changes in haematological parameters was statistically significant across the sampling time frame. However, red cell parameters (Packed cell volume, red blood cell count, and haemoglobin concentration) and Lymphocyte count were significantly depressed after XLB administration. All the haematological changes were restored to pre-anaesthetic values after 24hours. This study demonstrates that xylazine can be a beneficial alternative and desirable for emergencies in minor ruminant sedation.

Effectiveness of buccal administration of dexmedetomidine and ketamine combination in paediatric dental sedation: A randomized controlled clinical trial.

Pain and anxiety can be considerable obstacles while treating paediatric dental patients. Moderate sedation is needed to treat uncooperative patients. This study aimed to compare the effectiveness of buccal administration of dexmedetomidine-ketamine combination versus dexmedetomidine. Fifty-six uncooperative children were randomly assigned into two groups: Group I received buccal dexmedetomidine (2 μg/kg) and ketamine (2 mg/kg) (DEX-KET), whereas Group II received buccal dexmedetomidine (4 μg/kg) (DEX). The effects of drugs were evaluated based on changes in vital signs, onset and duration of sedation, sedation level, analgesia, ease of treatment and procedural adverse effects. There were no significant differences in vital signs or sedation onset between the two groups. DEX-KET group showed shorter recovery time than DEX group (p < .0001). There were no statistically significant differences between both groups regarding sedation level at optimum sedation and during operative procedure (p = .064, p = .069 respectively). The ease of treatment was significantly better in DEX-KET group than in DEX group (p = .048). Procedural side effects and analgesic effects of the sedative drugs were comparable between both groups. The combination of dexmedetomidine and ketamine delivered buccally provided a better method of delivering care to uncooperative children with more rapid recovery than dexmedetomidine.

Pengaruh Murottal Al-Qur’an tehadap Dosis Obat Anestesi Umum dan Waktu Pulih Sadar pada Pasien Operasi di Rumah Sakit Ibnu Sina Makassar

General anesthesia is used to facilitate surgery by providing hypnotic effects, analgesic effects, and muscle relaxation effects. To provide an adequate hypnotic, analgesia and relaxation effect, an adequate dose is needed. The time to recover consciousness after anesthesia is determined by the volume of fluid in the body, drug metabolism, half-life of the drug, age, and pre-anesthesia status. Murottal Al-Qur'an is a non-pharmacological therapy that can reduce stress hormones, increase feelings of relaxation, divert feelings of fear, improve the body's chemical balance thereby reducing hemodynamics. The aim of this study was to determine the effect of murottal Al-Qur'an on the dose of general anesthesia and the time to recover consciously in surgical patients at Ibnu Sina Hospital, Makassar. The research method is cross sectional with a quantitative approach. Each group measured the level of sedation using a Ramsay score of 3 or 4, then calculated the time to recover consciousness. The control group was given 1 mg ± 2 mg midazolam until they reached a Ramsay score of 3 or 4, the treatment group was given Al-Qur'an murottal and 1 mg ± 2 mg midazolam until they reached a Ramsay score of 3 or 4. So the time to recover consciousness and the onset of sedation was fast. These results show the influence of murottal Al-Qur'an on the dose of general anesthesia and the time to recover consciousness in surgical patients at Ibnu Sina Hospital Makassar.

Comparison of the effects of intranasal and intramuscular midazolam–butorphanol–ketamine on intraocular pressure, tear production and sedation in New Zealand White rabbits

ObjectiveTo compare the effects of intranasal (IN) and intramuscular (IM) midazolam–butorphanol–ketamine on intraocular pressure (IOP), tear production (TP) and sedation in rabbits. Study designProspective, randomized, crossover experimental study. AnimalsFourteen male New Zealand White rabbits, aged 1–2 years, body mass 3.1 ± 0.8 kg (mean ± standard deviation). MethodsRabbits were administered midazolam (1 mg kg–1), butorphanol (1.5 mg kg–1) and ketamine (5 mg kg–1) via IN and IM routes. IOP, TP and sedation scores were assessed at 0 (before drug administration), 5, 15, 30, 45 and 60 minutes after drug administration. Heart rate (HR), respiratory rate (fR), rectal temperature (RT), noninvasive mean arterial blood pressure (MAP) and peripheral hemoglobin oxygen saturation (SpO2) were simultaneously recorded until 45 minutes after drug administration. The onset and duration of sedation and sedation scores were recorded. ResultsDrug delivery route had no significant impact on mean IOP (p = 0.271) or TP (p = 0.062), and there were no significant changes over time for IOP (p = 0.711) or TP (p = 0.372). Similarly, delivery route had no significant impact on HR (p = 0.747), fR (p = 0.872), RT (p = 0.379), MAP (p = 0.217) and SpO2 (p = 0.254). Sedation onset was faster with IN (3.0 ± 1.0 minutes) than with IM administration (4.9 ± 0.7 minutes) (p = 0.011), but sedation duration was significantly longer with IM (52.6 ± 7.2 minutes) than with IN delivery (30.7 ± 6.8 minutes) (p = 0.004). There was no significant difference in sedation scores between the two delivery routes at any of the recorded time points. Conclusions and clinical relevanceThe combination of midazolam–butorphanol–ketamine had minimal impact on physiological and ocular variables regardless of the route of administration, whereas IN drug administration led to a shorter onset and duration of action than IM administration.

Safety and Efficacy of Intranasal Ketamine for Minor Pediatric Procedures: A Systemic Literature Review.

Compared to intravenous anesthetics, intranasalmedication for sedation is a less invasive approach. Intranasal ketamine (IK) is a widely used medication for procedural sedation. Hence, a systematic review was conducted with the aim of evaluating the safety and efficacy of IK among pediatric patients used for procedural sedation. For this purpose, a literature search was conducted on PubMed, Web of Science, and MEDLINE. A total of 247 search results appeared after running the developed query andeight articles passed through the inclusion and exclusion criteria and were included in the study. Most of the studies used 4 to 7 mg/kg dose of IK for pediatric patients. It was found that there was a moderate correlation between the age and dose of IK. Similarly, the dose of IK also had a direct and moderate correlation with the onset of sedation. Regarding the reported side effects, most of the studies reported nausea and vomiting as side effects of IK. Hence, it could be concluded from the study findings that effective sedation can be achieved by using 4 to 7 mg/kg dose of IK. The reported side effects ofIK were minor while parental satisfaction with the drug was very high. Therefore, it can be concluded that the use of IK for procedural sedation among pediatric patients is safe and effective.

One-Step Synthesis, Crystallography, and Acute Toxicity of Two Boron-Carbohydrate Adducts That Induce Sedation in Mice.

Boronic acids form diester bonds with cis-hydroxyl groups in carbohydrates. The formation of these adducts could impair the physical and chemical properties of precursors, even their biological activity. Two carbohydrate derivatives from d-fructose and d-arabinose and phenylboronic acid were synthesized in a straightforward one-step procedure and chemically characterized via spectroscopy and X-ray diffraction crystallography. Additionally, an acute toxicity test was performed to determine their lethal dose 50 (LD50) values by using Lorke's method. Analytical chemistry assays confirmed the formation of adducts by the generation of diester bonds with the β-d-pyranose of carbohydrates, including signals corresponding to the formation of new bonds, such as the stretching of B-O bonds. NMR spectra yielded information about the stereoselectivity in the synthesis reaction: Just one signal was found in the range for the anomeric carbon in the 13C NMR spectra of both adducts. The acute toxicity tests showed that the LD50 value for both compounds was 1265 mg/kg, while the effective dose 50 (ED50) for sedation was 531 mg/kg. However, differences were found in the onset and lapse of sedation. For example, the arabinose derivative induced sedation for more than 48 h at 600 mg/kg, while the fructose derivative induced sedation for less than 6 h at the same dose without the death of the mice. Thus, we report for the first time two boron-containing carbohydrate derivatives inducing sedation after intraperitoneal administration. They are bioactive and highly safe agents. Further biological evaluation is desirable to explore their medical applications.

Monitored anesthesia care: Dexmedetomidine-ketamine versus dexmedetomidine-propofol combination during burr-hole surgery for chronic subdural hematoma: A randomized trial

Background and Aim: Selecting the ideal drug combination for effective monitored anesthesia care to keep patients comfortable and safe during evacuation of chronic subdural hematoma is a challenge. Our hypothesis was that the combination of dexmedetomidine with ketamine might provide safer monitored anesthesia care keeping airway patency and stable hemodynamics in comparison to dexmedetomidine-propofol combination during burr-hole surgery for evacuating chronic subdural hematoma in high-risk patients.Methods: A total of 56 paticipants were allocated into two groups in this randomized prospective double-blind study by a computer-generated randomization table. DK group (n = 28): Patients were given a mix of ketamine (1 mg/kg) and dexmedetomidine (1 µg/kg) diluted in 10 ml of saline solution infused over 10 min as an intravenous bolus dose. This was followed by a continuous infusion of 0.5 µg/kg/h dexmedetomidine with 0.5 mg/kg/h ketamine. DP group (n = 28): Patients were given a mix of propofol (0.5 mg/kg) and dexmedetomidine (1 µg/kg) diluted in 10 ml of saline solution infused over 10 min as an intravenous bolus dose. This was followed by a continuous infusion of 0.5 µg/kg/h dexmedetomidine with 0.5 mg/kg/h propofol. The infused solutions were in two separate syringe pumps. The target was to achieve a modified Observer's Assessment of Alertness and Sedation score (OAA/S) of 3, and the infusion was stopped by finishing the skin suture.Results: The onset of sedation using OAA/S was significantly longer in the DK group (413.21 ± 49.18 s.) compared to (297.21 ± 37.68 s.) in the DP group. The number of participants with an airway obstruction score of 1 and 2 was significantly higher in the DK group compared to the DP group; however, those with a score of 3 were significantly higher in the DP group. The total number of patients needing intraoperative fentanyl was comparable between groups. The number of patients who developed intraoperative hypotension, bradycardia, bradypnea, and hypoxemia was significantly higher in the DP group compared to the DK group (p < 0.05). There was an improvement in postoperative Markwalder's Neurological Grading Scale (MNG) scores compared to preoperatively in both the DK and DP groups. The recovery time was significantly longer in the DK group (8.75 ± 1.17 min) compared to (5.73 ± 0.75 min) in the DP group, with comparable surgeon satisfaction.Conclusions: Combining dexmedetomidine with ketamine is safer than dexmedetomidine with propofol for effective monitored anesthesia care in high-risk patients undergoing burr-hole surgery for evacuating chronic subdural hematoma.Institutional Review Board approval (ref: 6434/25-10-2020).ClinicalTrials.gov (ref: NCT04621526, the date of registration: 9-11-2020).

Intranasal dexmedetomidine for sedation in ABR testing in children: No pain, big gain!

ObjectivesObtaining perfect immobility or sleep in children undergoing ABR auditory brainstem response) testing can be challenging. We examined the effectiveness and safety of intranasal dexmedetomidine for sedation of children undergoing ABR testing. Material and methodsWe included prospectively all patients aged from 1 to 15 years for whom sedation for ABR testing was required, between July 2018 and November 2021. We administered an initial dose of 2.5 μg/kg intranasal dexmedetomidine with a repeat dose of 1 μg/kg if needed 30 min later. Collected data included success rate of sedation, sedation onset and recovery times and incidence of side effects. ResultsABR testing was undertaken successfully in 57 of the 59 patients, giving a total success rate of 96,6 %. (95 % confidence interval 88.5 %–99.1 %). The median time to onset of sleep was 32 ± 18.3 min. The median duration of sedation recovery time was 48 ± 24.7 min. We recorded the adverse effects. Thirty-one patients experienced bradycardia and 28 patients experienced hypotension, all of which resolved without intervention. ConclusionIntranasal dexmedetomidine is an effective, safe, simple of use and noninvasive method for sedation in children. It could have a major role in auditory brainstem response testing, specially in the case of non-cooperative children. Registration number of the trialNCT03530371.

Comparative evaluation of intranasal dexmedetomidine, intranasal midazolam, and nitrous oxide for conscious sedation of anxious children undergoing dental treatment: A randomized cross-over trial.

Pharmacological methods, specifically sedatives, have gained popularity in managing the behavior of children during dental appointments. 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. 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. 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. 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.

Combined sedation in pediatric magnetic resonance imaging: determination of median effective dose of intranasal dexmedetomidine combined with oral midazolam

BackgroundThe exact median effective dose (ED50) of intranasal dexmedetomidine combined with oral midazolam sedation for magnetic resonance imaging (MRI) examination in children remains unknow and the aim of this study was to determine the ED50 of their combination.MethodsThis is a prospective dose-finding study. A total of 53 children aged from 2 months to 6 years scheduled for MRI examination from February 2023 to April 2023 were randomly divided into group D (to determine the ED50 of intranasal dexmedetomidine) and group M (to determine the ED50 of oral midazolam). The dosage of dexmedetomidine and midazolam was adjusted according to the modified Dixon’s up-and-down method, and the ED50 was calculated with a probit regression approach.ResultsThe ED50 of intranasal dexmedetomidine when combined with 0.5 mg∙kg− 1 oral midazolam was 0.39 µg∙kg− 1 [95% confidence interval (CI) 0.30 to 0.46 µg∙kg− 1] while the ED50 of oral midazolam was 0.17 mg∙kg− 1 (95% CI 0.01 to 0.29 mg∙kg− 1) when combined with 1 µg∙kg− 1 intranasal dexmedetomidine. The sedation onset time of children with successful sedation in group D was longer than in group M (30.0[25.0, 38.0]vs 19.5[15.0, 35.0] min, P < 0.05). No other adverse effects were observed in the day and 24 h after medication except one dysphoria.ConclusionThis drug combination sedation regimen appears suitable for children scheduled for MRI examinations, offering a more precise approach to guide the clinical use of sedative drugs in children.Trial registrationChinese Clinical Trial Registry, identifier: ChiCTR2300068611(24/02/2023).

Clinico-Physiological and Haemodynamic Alterations Following Propofol Induction and Premedication with Butorphanol, Dexmedetomidine or Acepromazine in Dogs

The present study was conducted during February-October 2021 at Department of Veterinary Surgery and Radiology, College of Veterinary Science &amp; A.H. Anjora, Durg (C.G.), India to evaluate the alternations on clinico-physiological and haemodynamic parameters following propofol induction in dogs premedicated with butorphanol or dexmedetomidine or acepromazine. Eighteen adult dogs of either sex were randomly divided into three groups (BP, DP and AP) with six animals in each. Ten minutes prior to the anaesthetic administration, all the dogs were administered glycopyrrolate @ 0.02 mg kg-1 I/M. The animals of group BP, DP and AP were premedicated intramuscularly with butorphanol @ 0.3 mg kg-1 b.wt., dexmedetomidine @ 10 µg kg-1 b.wt. and acepromazine @ 0.4 mg kg-1 b.wt. respectively. General anaesthesia was induced with propofol @ 7 mg kg-1 b.wt. intravenously. Clinical parameters were recorded following induction with propofol. Physiological and haemodynamic parameters were recorded before (0), 5 min. after sedation, induction and at 10, 20, 40, 60 and 120 min. post propofol anaesthesia. The onset of sedation and anaesthesia was quicker in group DP followed by AP and BP. Duration of anaesthesia and complete recovery were significantly (p&lt;0.05) longer in group DP as compared to group BP and AP. The physiological and haemodynamic parameters showed transient changes which were compensated and remained within normal range during the study period without producing any deleterious effect. Thus, propofol can be safely used as induction agent in dogs premedicated with either dexmedetomidine or butorphanol or acepromazine and does not produce any adverse effect on cardiopulmonary system. However, dexmedetomidine-propofol combination provided longer duration of anaesthesia in dogs as compared to other groups.

Effects of intranasal and intramuscular administration of butorphanol and zolazepam-tiletamine combination on intraocular pressure and tear secretion in New Zealand White rabbits.

This study aimed to compare the effect of intranasal (IN) and intramuscular (IM) administration of butorphanol and zolazepam-tiletamine (ZT) combination on intraocular pressure (IOP) and tear secretion (TS) in rabbits. Fourteen healthy male New Zealand White rabbits weighing 3.05 ± 0.72 kg, aged between 1 and 2 years old, were included in the study. Animals randomly received 0.5 mg/kg butorphanol and 15 mg/kg ZT combination either with IN or IM administration. IOP and TS were measured at baseline (T0), and followed by 5, 15, 30, 45, and 60 min after drug administration. The sedation variables, the time to onset of sedation, duration of sedation, and sedation scores were also recorded. The route of administration for the butorphanol and ZT combination had no significant effect on the mean IOP (p = .301) and TS (p = .445). Furthermore, there were no significant changes observed in the IOP (p = .472) and TS (p = .348) over time. The time to onset of sedation was earlier in the IN group (4.57 ± 0.79 min) than in the IM group (5.86 ± 0.9 min; p = .0004). The duration of sedation was significantly longer for IM (57.43 ± 3.41 min) compared with IN (45.0 ± 1.91 min; p < .0001). No significant difference in the sedation score was observed between groups at all time points. In conclusion, both IN and IM administration of the butorphanol and ZT combination in rabbits had similar effects on IOP and TS.

Identification of an effective and safe bolus dose and lockout time for patient-controlled sedation (PCS) using dexmedetomidine in dental treatments: a randomized clinical trial.

This study investigated a safe and effective bolus dose and lockout time for patient-controlled sedation (PCS) with dexmedetomidine for dental treatments. The depth of sedation, vital signs, and patient satisfaction were investigated to demonstrate safety. Thirty patients requiring dental scaling were enrolled and randomly divided into three groups based on bolus doses and lockout times: group 1 (low dose group, bolus dose 0.05 µg/kg, 1-minute lockout time), group 2 (middle dose group, 0.1 µg/kg, 1-minute), and group 3 (high dose group, 0.2 µg/kg, 3-minute) (n = 10 each). ECG, pulse, oxygen saturation, blood pressure, end-tidal CO2, respiratory rate, and bispectral index scores (BIS) were measured and recorded. The study was conducted in two stages: the first involved sedation without dental treatment and the second included sedation with dental scaling. Patients were instructed to press the drug demand button every 10 s, and the process of falling asleep and waking up was repeated 1-5 times. In the second stage, during dental scaling, patients were instructed to press the drug demand button. Loss of responsiveness (LOR) was defined as failure to respond to auditory stimuli six times, determining sleep onset. Patient and dentist satisfaction were assessed before and after experimentation. Thirty patients (22 males) participated in the study. Scaling was performed in 29 patients after excluding one who experienced dizziness during the first stage. The average number of drug administrations until first LOR was significantly lower in group 3 (2.8 times) than groups 1 and 2 (8.0 and 6.5 times, respectively). The time taken to reach the LOR showed no difference between groups. During the second stage, the average time required to reach the LOR during scaling was 583.4 seconds. The effect site concentrations (Ce) was significantly lower in group 1 than groups 2 and 3. In the participant survey on PCS, 8/10 in group 3 reported partial memory loss, whereas 17/20 in groups 1 and 2 recalled the procedure fully or partially. PCS with dexmedetomidine can provide a rapid onset of sedation, safe vital sign management, and minimal side effects, thus facilitating smooth dental sedation.

A dose characterization study evaluating the pharmacodynamics and safety of a concentrated alfaxalone solution (4%) as an intramuscular sedative in dogs.

Alfaxalone is a commonly employed veterinary anaesthetic induction and sedation agent. A 4% w/v preserved, aqueous formulation of alfaxalone 'RD0387' (A4%) has recently been developed. To evaluate the sedative effects of A4%, three doses, 5 mg kg-1 (A5); 7.5 mg kg-1 (A7.5) and 10 mg kg-1 (A10) were administered intramuscularly into the epaxial musculature of six healthy adult mixed-breed dogs in an experimental, randomized, blinded, crossover study. Sedation time variables, quality of sedation (including onset of sedation and recovery), physiological variables, response to cephalic vein catheterization and frequency of undesirable events were recorded. Continuous variables were analysed between treatments (one-way ANOVA or restricted maximum likelihood modelling) and within treatments compared with baseline (Tukey's test). Categorical data were analysed between treatments (Kruskal-Wallis' test) and within treatments from baseline (Dunn's test). Significance was set at p < .05. All dogs became sedated (laterally recumbent) and sedation onset was significantly faster in groups A7.5 (9.8 ± 5.3 min) and A10 (9.1 ± 5.6 min) compared to A5 (25.6 ± 16.1 min) (p = .033, p = .027, respectively). Duration of sedation was significantly longer in A10 (168.5 ± 70.6 min) and A7.5 (143.8 ± 58 min) compared to A5 (63.8 ± 28.2 min) (p = .005 and p = .003, respectively). Dogs in A10 had a superior quality of onset of sedation compared to A5 (p = .028). Sedation scores and quality of recovery from sedation were not significantly different between doses. Two dogs (2/6) in A5 were insufficiently sedated for cephalic catheterization. Ataxia was the most frequently observed undesirable event with an overall frequency of 78% (14/18) and 89% (16/18) during sedation onset and recovery, respectively. Overall, A4% administered IM in dogs at 7.5 and 10 mg kg-1 resulted in sufficient sedation for IV catheterization in dogs. To improve the speed and quality of the sedation, it is recommended that future research focuses on combining A4% with other sedative or analgesic drugs.

Correlating the Depth of Sedation Between the Ramsay Sedation Scale and Bispectral Index Using Either Intravenous Midazolam or Intravenous Propofol in Elderly Patients Under Spinal Anaesthesia.

Supplementation of spinal anaesthesia with sedatives or anxiolytics has emerged as a standard protocol to alleviate patients' anxiety and to produce amnesia during the surgical procedure. Thus, judicious use of sedation can make surgeries under spinal anaesthesia more comfortable and acceptable for the elderly patient, the surgeon, and the anaesthesiologist. However, over-sedation may jeopardise the safety of the patient. Appropriate sedation helps reduce physiological stress, which leads to a better result. Therefore, monitoring the depth of sedation becomes essential. The Ramsay sedation scale (RSS) and bispectral index (BIS) both are used widely to assess the depth of sedation. The primary objective of the study was to assess and correlate the depth of sedation between the BIS and RSS in elderly patients using midazolam and propofol under spinal anaesthesia. The secondary objectives were to observe any difference in the commencement of sedation between the two groups and to observe haemodynamic changes between the two groups. A total of 60 elderly patients undergoing urological procedures under spinal anaesthesia were randomly assigned to receive either midazolam (Group A, n=30) or propofol (Group B, n=30) for sedation. In Group A, patients were given an initial bolus of midazolam 0.03 mg/kg and a maintenance incremental bolus of 0.01 mg/kg up to a maximum of 2.5 mg in 10-minute intervals. Group B used propofol with an initial bolus dose of 0.5 mg/kg over two minutes and a maintenance bolus of 10-20 mg as required for the maintenance of sedation depth. Sedation was titrated to achieve a BIS score of 70-80 and an RSS score of 3-4. Heart rate, non-invasive systolic, diastolic, mean arterial blood pressure, oxygen saturation (SPO2), and the correlation coefficient between the BIS and RSS were measured at 0 (baseline), 5, 10, 20, 30, 40, 50, and 60 minutes of interval. The correlation coefficient between the BIS and RSS scores in Group A at various time intervals indicate a strong correlation coefficient of -0.76 at five minutes, -0.64 at 20 minutes, -0.78 at 30 minutes, -0.56 at 40 minutes, and -0.39 at 50 minutes. In Group B, the correlation coefficient between the BIS and RSS scores at various time intervals indicate a strong correlation coefficient of -0.75 at five minutes, -0.76 at 20 minutes,-0.64 at 30 minutes, -0.89 at 40 minutes, and -0.46 at 50 minutes of interval. We also observed that the BIS drops to a lower level in patients receiving propofol (Group B) with a significant difference depicting early onset of sedation with propofol. In Group B, HR and MAP were significantly less than those of Group A. There was no significant difference in terms of mean age, sex, and body weight in the patients of both groups. The BIS and RSS scores indicate a strong correlation with a magnitude of 70%-80%, but more in Group B (propofol) than Group A (midazolam). Therefore, the characteristics of each sedative drug can influence the level of sedation during spinal anaesthesia. Clinicians should use a combination of BIS values and other objective sedative methods to determine the degree of sedation, rather than relying exclusively on BIS values.