OBJECTIVE: To compare the median effective dose (ED) of intranasal dexmedetomidine for procedural sedation in uncooperative pediatric patients with acyanotic congenital heart disease before and after cardiac surgery. METHODS: We prospectively recruited 47 children (22 in preoperative group and 25 in postoperative group) who needed sedation for transthoracic echocardiography (TTE). A modified up-and-down sequential study design was employed to determine dexmedetomidine dose for each patient with a starting dose of 2 μg/kg in both groups; dexmedetomidine doses for subsequent subjects were determined according to the responses from the previous subject using the up-and-down method at a 0.25 μg/kg interval. The ED was determined using probit regression. The onset time, examination time, wake-up time and adverse effects were measured, and the safety was evaluated in terms of changes in vital signs every 5 min. RESULTS: The ED value of intranasal dexmedetomidine for sedation was 1.84 μg/kg (95% : 1.68-2.00 μg/kg) in children with congenital heart disease before cardiac surgery, and 3.38 μg/kg (95% : 3.21-3.54 μg/kg) after the surgery. No significant difference was found between the two groups in the demographic variables, onset time, examination time, wake-up time, or adverse effects. CONCLUSIONS In children with acyanotic congenital heart disease, the ED of intranasal dexmedetomidine for TTE sedation increases to 3.38 μg/ kg after cardiac surgery from the preoperative value of 1.84 μg/kg.
Administration, Intranasal ; Cardiac Surgical Procedures ; Child ; Dexmedetomidine ; Heart Defects, Congenital ; surgery ; Humans ; Hypnotics and Sedatives

PURPOSE: To investigate whether dexmedetomidine (Dex) can reduce the production of inflammatory factor IL-1β by inhibiting the activation of NLRP3 inflammasome in hippocampal microglia, thereby alleviating the inflammatory response of the central nervous system induced by surgical injury. METHODS: Exploratory laparotomy was used in experimental models in this study. Totally 48 Sprague Dawley male rats were randomly divided into 4 groups (n = 12 for each), respectively sham control (group A), laparotomy only (group B); and Dex treatment with different doses of 5 μg/kg (group D1) or 10 μg/kg (group D2). Rats in groups D1 and D2 were intraperitoneally injected with corresponding doses of Dex every 6 h. The rats were sacrificed 12 h after operation; the hippocampus tissues were isolated, and frozen sections were made. The microglia activation was estimated by immunohistochemistry. The protein expression of NLRP3, caspase-1, ASC and IL-1β were detected by immunoblotting. All data were presented as mean ± standard deviation, and independent sample t test was used to analyze the statistical difference between groups. RESULTS: The activated microglia in the hippocampus of the rats significantly increased after laparotomy (group B vs. sham control, p < 0.01). After Dex treatment, the number was decreased in a dose-dependent way (group D1 vs. D2, p < 0.05), however the activated microglia in both groups were still higher than that of sham controls (both p < 0.05). Further Western blot analysis showed that the protein expression levels of NLRP3, caspase-1, ASC and downstream cytokine IL-1β in the hippocampus from the laparotomy group were significantly higher than those of the sham control group (all p < 0.01). The elevated expression of these proteins was relieved after Dex treatment, also in a dose-dependent way (D2 vs. D1 group, p < 0.05). CONCLUSION Dex can inhibit the activation of microglia and NLRP3 inflammasome in the hippocampus of rats after operation, and the synthesis and secretion of IL-1β are also reduced in a dose-dependent manner by using Dex. Hence, Dex can alleviate inflammation activation on the central nervous system induced by surgical injury.
Animals ; Dexmedetomidine ; administration & dosage ; pharmacology ; Dose-Response Relationship, Drug ; Hippocampus ; metabolism ; Immunohistochemistry ; Inflammasomes ; metabolism ; Inflammation Mediators ; metabolism ; Injections, Intraperitoneal ; Interleukin-1beta ; metabolism ; Laparotomy ; adverse effects ; Male ; Microglia ; metabolism ; NLR Family, Pyrin Domain-Containing 3 Protein ; metabolism ; Rats, Sprague-Dawley ; Time Factors

Objective To investigate the 50% effective dose(ED)and 95% effective dose(ED)of dexmedetomidine(DEX)combined with 0.032 μg/(kg·h)sufentanil as well as its analgesic effect for patient-controlled intravenous analgesia(PCIA)after video-assisted thoracoscopic surgery(VATS).Methods Totally 25 patients undergoing elective VATS were enrolled. DEX and 0.032 μg/(kg·h)sufentanil were used for postoperative PCIA. The loading dose of DEX was 0.048 μg/(kg·h),and the dose difference between two adjacent patients was 0.008 μg/(kg·h). The DEX dose of a current patient was determined by whether the previous patient was satisfied with postoperative analgesic effect. If the previous patient was satisfied with postoperative analgesic effect,the DEX dose of the current patient was decreased by 0.008 μg/(kg·h);and if the previous analgestic effect was not satisfactory,DEX dose of the current patient was increased by 0.008 μg/(kg·h). The study endpoint was dexmedetomidine dose was<0.008 μg/(kg· h) within 7 upper and lower cycles in 7 consecutive cases. Finally,the probability unit regression was used to estimate the ED and ED of DEX and their 95% .Results When DEX combined with 0.032 μg/(kg·h) sufentanil was used for postoperative PCIA in young patients undergoing VATS,the ED and EDof DEX were 0.0346 μg/(kg· h)[95%:0.0283-0.0408 μg/(kg·h)] and 0.0459 μg/(kg·h)[95%:0.0400-0.0880 μg/(kg·h)],respectively. No adverse reaction such as vomiting,respiratory depression,or bradycardia occurred. The average Visual Analogue Scale(VAS)scores at rest(=-5.128,=0.000)and cough(Z=-6.642,=0.000)and the Ramsay sedation score(Z=-2.335,=0.020)within 6 hours after surgery were higher than those after 6 hour.Conclusion DEX combined with 0.032 μg/(kg·h) sufentanil are effective for postoperative PCIA in patients undergoing VATS when the ED and ED are 0.0346 μg/(kg·h)and 0.0459 μg/(kg·h),respectively.
Analgesia, Patient-Controlled ; Analgesics, Non-Narcotic ; administration & dosage ; therapeutic use ; Dexmedetomidine ; administration & dosage ; therapeutic use ; Dose-Response Relationship, Drug ; Drug Therapy, Combination ; Humans ; Pain, Postoperative ; drug therapy ; Sufentanil ; administration & dosage ; therapeutic use ; Thoracic Surgery, Video-Assisted

OBJECTIVE: To observe the preoperative sedation, the status of separation from parents, compliance with the mask, hemodynamic parameters and postoperative agitation of intranasal dexmedetomidine (DEX) premedication on children undergoing dental rehabilitation under general anesthesia. METHODS: In the study, 60 children of American Society of Anesthesiology classification (ASA I-II), aged 2-9 years, were randomly assigned to one of two equal groups. Thirty minutes before operation, control group received intranasal placebo (0.9% saline) 0.02 mL/kg, and DEX group received intranasal DEX 2 μg/kg. The preoperative sedation score, the status of separation from parents, compliance with the mask and hemodynamic parameters were recorded by an anesthesiologists until anesthesia induction. Recovery conditions, postoperative agitation were also recorded. RESULTS: There was no significant difference between the two groups in patient characteristics, operation time, extubation time and recovery time. Compared with the children in control group, those in DEX group were significantly more sedated when they were separated from their parents (56.7% vs. 26.7%, P<0.05). Satisfactory compliance with mask application was 40% in control group vs. 73.3% in DEX group (P<0.05). There was no significant difference between the two groups regarding the incidences of postoperative agitation and oxygen saturation (SpO₂). Compared with control group, the heart rate (HR) of DEX group was decreased after 20 minutes of drug administration [(97.13±12.93) beats/min vs.(104.53±11.97) beats/min, P<0.05]. The changes of the HR and SpO2 in the two groups were within the normal range. There were no incidences of bradycardia and hypoxemia in either of the groups during study observation. CONCLUSION Premedication with intranasal DEX 2 μg/kg for children undergoing dental rehabilitation under general anesthesia produces good preoperative sedation. The levels of sedation, scores of parental separation and compliance with the mask were satisfied. The children have good recovery conditions, and no obvious postoperative agitation and respiratory depression after DEX administration. Intranasal DEX 2 μg/kg is an effective and safe alternative for premedication in children.
Administration, Intranasal ; Anesthesia, General ; Child ; Child, Preschool ; Dental Restoration, Permanent/methods* ; Dexmedetomidine/administration & dosage* ; Double-Blind Method ; Heart Rate ; Humans ; Hypnotics and Sedatives/administration & dosage*

BACKGROUND: The most important reason for pre-operative administration of medication is to reduce anxiety. Alleviation of fear and anxiety about surgery enables patients to remain comfortable during treatment. Dexmedetomidine (DEX) is a fast-acting drug that is used as a premedication in different circumstances because it has sedative and anti-anxiolytic effects, and stable hemodynamics. It also has the advantage of intranasal administration. The aim of this study was to investigate the effects and hemodynamic stability of DEX by retrospectively analyzing cases in which DEX was administered nasally as a premedication. METHODS: Ten patients treated at Dankook University Dental Hospital, recruited between February and April 2015, received intranasal delivery of 2 µg/kg DEX, 30 minutes prior to general anesthesia. Anesthesia records of anxiety, blood pressure, respiration, pulse, estimated arterial oxygen saturation (SpO2), and partial pressure, or maximum concentration, of carbon dioxide (ETCO2) were analyzed. RESULTS: Administration of DEX prior to a general anesthetic effectively relieved anxiety. Respiratory depression, the most severe adverse effect of other sedatives, was not observed. Hemodynamic stability under general anesthesia was maintained during treatment and a reduction in emergence delirium was observed upon completion of treatment. CONCLUSIONS: Premedication administration of DEX is safe for pediatric patients undergoing dental treatment under general anesthesia.
Administration, Intranasal* ; Anesthesia ; Anesthesia, General* ; Anesthetics ; Anxiety ; Blood Pressure ; Carbon Dioxide ; Delirium ; Dexmedetomidine* ; Hemodynamics ; Humans ; Hypnotics and Sedatives ; Oxygen ; Partial Pressure ; Premedication* ; Respiration ; Respiratory Insufficiency ; Retrospective Studies

Increased intraocular pressure (IOP) during surgery is a risk factor for postoperative ophthalmological complications. We assessed the efficacy of systemically infused dexmedetomidine in preventing the increase in IOP caused by a steep Trendelenburg position, and evaluated the influence of underlying hypertension on IOP during surgery. Sixty patients undergoing laparoscopic surgery in a steep Trendelenburg position were included. Patients in the dexmedetomidine group received a 1.0 µg/kg IV loading dose of dexmedetomidine before anesthesia, followed by an infusion of 0.5 µg/kg/hr throughout the operation. Patients in the saline group were infused with the same volume of normal saline. IOP and ocular perfusion pressure (OPP) were measured 16 times pre- and intraoperatively. In the saline group, IOP increased in the steep Trendelenburg position, and was 11.3 mmHg higher at the end of the time at the position compared with the baseline value (before anesthetic induction). This increase in IOP was attenuated in the dexmedetomidine group, for which IOP was only 4.2 mmHg higher (P < 0.001 vs. the saline group). The steep Trendelenburg position was associated with a decrease in OPP; the degree of decrease was comparable for both groups. In intragroup comparisons between patients with underlying hypertension and normotensive patients, the values of IOP at every time point were comparable. Dexmedetomidine infusion attenuated the increase in IOP during laparoscopic surgery in a steep Trendelenburg position, without further decreasing the OPP. Systemic hypertension did not seem to be associated with any additional increase in IOP during surgery. (Registration at the Clinical Research Information Service of Korea National Institute of Health ID: KCT0001482)
Aged ; Dexmedetomidine/administration & dosage/*pharmacology ; Double-Blind Method ; Eye Diseases/surgery ; Female ; Head-Down Tilt ; Humans ; Hypnotics and Sedatives/administration & dosage/pharmacology ; Intraocular Pressure/*drug effects ; Intraoperative Complications/drug therapy/prevention & control ; Laparoscopy ; Male ; Middle Aged ; Prospective Studies ; Risk Factors ; Tonometry, Ocular ; Treatment Outcome

PURPOSETo evaluate midazolam sequential with dexmedetomidine for agitated patients undergoing weaning to implement light sedation in ICU.

METHODSThis randomized, prospective study was conducted in Tianjin Third Central Hospital, China. Using a sealed-envelope method, the patients were randomly divided into 2 groups (40 patients per group). Each patient of group A received an initial loading dose of midazolam at 0.3-3mg/kg·h 24 h before extubation, followed by an infusion of dexmedetomidine at a rate of 0.2-1 μg/kg·h until extubation. Each patient of group B received midazolam at a dose of 0.3-3 mg/kg·h until extubation. The dose of sedation was regulated according to RASS sedative scores maintaining in the range of -2-1. All patients were continuously monitored for 60 min after extubation. During the course, heart rate (HR), mean artery pressure (MAP), extubation time, adverse reactions, ICU stay, and hospital stay were observed and recorded continuously at the following time points: 24 h before extubation (T1), 12 h before extubation (T2), extubation (T3), 30 min after extubation (T4), 60 min after extubation (T5).

RESULTSBoth groups reached the goal of sedation needed for ICU patients. Dexmedetomidine was associated with a significant increase in extubation quality compared with midazolam, reflected in the prevalence of delirium after extubation (20% (8/40) vs 45% (18/40)), respectively (p= 0.017). There were no clinically significant decreases in HR and MAP after infusing dexmedetomidine or midazolam. In the group A, HR was not significantly increased after extubation; however, in the group B, HR was significantly increased compared with the preextubation values (p < 0.05). HR was significantly higher in the group B compared with the group A at 30 and 60 min after extubation (both, p <0.05). Compared with preextubation values, MAP was significantly increased at extubation in the group B (p < 0.05) and MAP was significantly higher at T3, T4, T5 in the group B than group A (p < 0.05). There was a significant difference in extubation time ((3.0 ± 1.5) d vs (4.3 ± 2.2) d, p < 0.05), ICU stay ((5.4 ± 2.1) d vs (8.0 ± 1.4) d, p < 0.05), hospital stay ((10.1 ± 3.0) d vs (15.3 ± 2.6) d, p <0.05) between group A and B.

CONCLUSIONMidazolam sequential with dexmedetomidine can reach the goal of sedation for ICU agitated patients, meanwhile it can maintain the respiratory and circulation parameters and reduce adverse reactions.

Adult ; Aged ; Critical Care ; methods ; Delirium ; drug therapy ; etiology ; Dexmedetomidine ; administration & dosage ; Female ; Humans ; Hypnotics and Sedatives ; administration & dosage ; Intensive Care Units ; Length of Stay ; Male ; Midazolam ; administration & dosage ; Middle Aged ; Prognosis ; Prospective Studies ; Respiration, Artificial ; adverse effects ; methods ; Risk Assessment ; Statistics, Nonparametric ; Treatment Outcome ; Ventilator Weaning ; adverse effects ; psychology

Dentists often sedate patients in order to reduce their dental phobia and stress during dental treatment. Sedatives are administered through various routes such as oral, inhalation, and intravenous routes. Intravenous administration has the advantage of rapid onset of action, predictable duration of action, and easy titration. Typically, midazolam, propofol or dexmedetomidine are used as intravenous sedatives. Administration of these sedatives via infusion by using a syringe pump is more effective and successful than infusing them as a bolus. However, during intravenous infusion of sedatives or opioids using a syringe pump, fatal accidents may occur due to the clinician's carelessness. To prevent such risks, smart syringe pumps have been introduced clinically. They allow clinicians to perform effective sedation by using a computer to control the dose of the drug being infused. To ensure patient safety, various alarm features along with a drug library, which provides drug information and prevents excessive infusion by limiting the dose, have been added to smart pumps. In addition, programmed infusion systems and target-controlled infusion systems have also been developed to enable effective administration of sedatives. Patient-controlled infusion, which allows a patient to control his/her level of sedation through self-infusion, has also been developed. Safer and more successful sedation may be achieved by fully utilizing these new features of the smart pump.
Administration, Intravenous ; Analgesics, Opioid ; Dental Anxiety ; Dentists ; Dexmedetomidine ; Humans ; Hypnotics and Sedatives ; Infusion Pumps ; Infusions, Intravenous ; Inhalation ; Midazolam ; Patient Safety ; Propofol ; Syringes*

Objective To observe the effects of two different intranasal dexmedetomidine doses as premedication on the ECof sevoflurane for successful laryngeal mask airway placement in children. Methods Children aged 3-6 years, of American Society of Anesthesiologists physical status 1, and scheduled for plastic surgery were enrolled in this study. Children were assigned to receive either spray administration of intranasal dexmedetomidine 1 μg/kg (group D1, n=21) or 2 μg/kg (group D2, n=20) approximately 30 minutes before anesthesia. Anesthesia was induced with sevoflurane up to 8% in 100% O, with fresh gas flow set to 6 L/min. After the pupil fixed to the middle position, sevoflurane dial setting was reduced to 5% and fresh gas flow reduced to 3 L/min. The endtidal sevofluran (ET) concentration for laryngeal mask airway insertion sustained for 10 minutes after vein intubation, which was determined according to the Dixon's up and down method. The initial endtidal sevoflurane concentration in each group was set at 2%. ETwas increased/decreased (1:1.2) in the next patient according to the response to laryngeal mask airway insertion. Bispectral index, mask acceptance, all response to laryngeal mask airway insertion, and ETof laryngeal mask airway insertion of children were recorded. Results The bispectral index value was 77.4±3.6 in group D2, which was significantly lower than that (87.4±1.9) in group D1 when children entered operation room (P<0.05). Mask acceptance was 76.2% in group D1 and 90.0% in group D2. The ECof sevoflurane for laryngeal mask airway insertion was 1.09% (95% CI=0.89%-1.28%) in group D2, which was lower than 1.59% (95% CI=1.41%-1.78%) in group D1 (P<0.05). Conclusion Compared with the dose of 1 μg/kg, spray administration of intranasal dexmedetomidine 2 μg/kg as premedication can reduce the sevoflurane ECfor successful laryngeal mask airway placement in children.
Administration, Intranasal ; Anesthesia ; Anesthetics, Inhalation ; administration & dosage ; Child ; Child, Preschool ; Dexmedetomidine ; administration & dosage ; Humans ; Laryngeal Masks ; Methyl Ethers ; administration & dosage

Objective To compare two spray administration of intranasal dexmedetomidine (DEX) doses for premedication in children. Methods In this prospective,randomized,double-blind study,41 children aged 3-6 years were enrolled. Children were assigned to receive either spray administration of intranasal DEX 1 μg/kg (Group D1) or 2 μg/kg (Group D2). The Ramsay Sedation Scale scores were evaluated at 5 min intervals. Sedation status at separation from patient was also evaluated. Heart rate (HR) and saturation of peripheral oxygen (SpO) were recorded before and every 15 min after drug administration. Results The median sedation onset time was 30 min and 20 min in group D1 and group D2,respectively. Compared with the children in group D1,those in group D2 were significantly more sedated when they were separated from their parents (61.9% vs. 95.0%,respectively)(χ=5.549,P=0.010). In Group D2,the HR decreased by 15.8% (t=2.415,P=0.021) 30 min after the spray administration of intranasal DEX. Compared with the baseline values,there was no significant difference in both groups in terms of SpO(t=-1.426,P=0.162;t=-1.096,P=0.280)and HR in group D1 (t=-0.299,P=0.767) 30 min after the spray administration of intranasal DEX. Conclusion Spray administration of intranasal DEX 2 μg/kg provides superior sedation in children.
Administration, Intranasal ; Anesthesia ; methods ; Child ; Child, Preschool ; Dexmedetomidine ; administration & dosage ; Double-Blind Method ; Female ; Heart Rate ; Humans ; Hypnotics and Sedatives ; administration & dosage ; Male ; Oxygen ; analysis ; Prospective Studies