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

Objective To evaluate the safety and effectiveness of oral midazolam sedation combined nitrous oxide sedation for reducing dental fear in children.Methods Totally 77 children with a Frankl's Behavior Rating Scale score of 1 were included in this study,among whom 41 received a total of 78 person-times of oral midazolam sedation (0.50-0.75 mg·kg ) (midazolam group) and 36 children were treated with the combination of 0.4 mg/kg oral midazolam with 30%-40% nitrous oxide (totally 73 person-times)(combination group). At each visit,heart rate,arterial oxygen saturation,and treatments were recorded. The behaviors of children during the treatment were assessed by Frankl's Behavior Rating Scale,the completion of treatment was assessed by Houpt Scale,and the sedation status was assessed by Ramsay Scale. Telephone follow-up was performed to record the side effects 24 hours after treatment. Results The vital signs were stable among all the 77 subjects,with a Ramsay score of 2 or 3. In the midazolam group, the behaviors were cooperative in 52 person-times (66.7%) and not cooperative in 26 person-times (33.3%);the planned treatments were completed in 62 person-times (79.5%) and partially completed in 16 person-times(20.5%). In the combination group,the behaviors were cooperative in 56 person-times (76.7%) and not cooperative in 17 person-times (23.3%);64 person-times (87.7%) completed the planned treatments and 9 person-times (12.3%) partially completed the treatments. The success rates of sedation (χ =1.87,P= 0.17) and treatment (χ =1.83,P= 0.18) were not significantly different between these two groups. The median Frankl scale score was significantly higher in the combination group [3 (3,4)] than in the midazolam group [3 (2,4)] (Z=2.647,P=0.008]. The median score of Houpt scale in the combination group [5(4,6)] was also significantly higher than in midazolam group [5(3,5)] (Z=2.236,P=0.026]. In midazolam group,there were 7 person-times of dysphoria,3 person-times of diplopia,and 2 person-times of hiccough among 78 person-times;in the combination group,there were 5 person-times of dysphoria,5 person-times of diplopia,1 person-time of hiccough,and 2 person-times of vomit among 73 person-times of treatment. Thus,there was no significant difference in the incidence of side effects (15.4% vs.17.8%,χ =0.160,P=0.689). Logistic regression analysis showed that the success rate of treatment was not associated with sex (OR=1.704,P=0.174),dose (OR=1.289,P=0.516),and treatment types (OR=0.555,P=0.143). Children over 3 years old had a significantly high success rate than those under 3 years old (OR=3.372,P=0.011). Conclusions Oral midazolam is safe and effective for reducing dental fear in children. The combination of oral midazolam with 30%-40% nitrous oxide can improve the behaviors of children during the dental treatment,especially in children over 3 years old.
Administration, Oral ; Anesthesia, Dental ; Child ; Child, Preschool ; Conscious Sedation ; Cross-Over Studies ; Dental Anxiety ; Humans ; Hypnotics and Sedatives ; Midazolam ; therapeutic use ; Nitrous Oxide

3-Carene, a bicyclic monoterpene, is one of the major components of the pine tree essential oils. It has been reported that, in addition to its known properties as a phytoncide, 3-carene has anti-inflammatory, antimicrobial, and anxiolytic effects. We have previously demonstrated that α-pinene, the major component of pine tree, has a hypnotic effect through GABA(A)-benzodiazepine (BZD) receptors. However, a hypnotic effect of 3-carene has not been studied yet. Here, we report that oral administration of 3-carene increases the sleep duration and reduces sleep latency in pentobarbital-induced sleep test. 3-Carene potentiates the GABA(A) receptor-mediated synaptic responses by prolonging the decay time constant of inhibitory synaptic responses. These enhancing effects of 3-carene are reproduced by zolpidem, a modulator for GABA(A)-BZD receptor, and fully inhibited by flumazenil, an antagonist for GABA(A)-BZD receptor. The molecular docking of 3-carene to the BZD site of GABA(A) protein structure, suggests that 3-carene binds to the BZD site of α1 and ϒ2 subunits of GABA(A)-BZD receptor. These results indicate that, similar to α-pinene, 3-carene shows a sleep-enhancing effect by acting as a positive modulator for GABA(A)-BZD receptor.
Administration, Oral ; Anti-Anxiety Agents ; Flumazenil ; Hypnotics and Sedatives ; Oils, Volatile ; Pinus

OBJECTIVE: To explore the effects of propofol sedation on psychological stress in patients undergoing surgery under epidural anesthesia. METHODS: Sixty patients scheduled to undergo elective ileostomy closure under epidural anesthesia were randomized into propofol sedation group and control group (=30). The patients in the sedation group received a loading dose of propofol of 0.6 mg·kg· h followed by a maintenance dose with continuous infusion of 3 mg·kg· h given after the Observer's Assessment of Alertness/Sedation (OAA/S) score reached 2-3. An equivalent volume of normal saline was administered in patients in the control group. The patients' preoperative and intraoperative anxiety scores were assessed with the State Anxiety Inventory (SAI) on the day before and on the first day after the surgery, respectively. The mean blood pressure (MBP), heart rate (HR), SpO, OAA/S, and the indicators of psychological stress of brain functional state of the patients (including the wavelet index [WLi], anxiety index [ANXi], comfortable index [CFi] and pain index [Pi]) were recorded at 5 min after entering the operating room (T), at the time of lumbar puncture (T) and change to supine position after the puncture (T), at 20 s (T), 40 s (T), and 60 s (T) after intravenous administration, and at 2 min (T), 4 min (T), 6 min (T), 8 min (T), 10 min (T) and 40 min (T) after skin incision. The patient's satisfaction with anesthesia was assessed with the Visual Analog Scale (VAS) score on the first day after the operation. Serum cortisol level was measured before anesthesia and at the end of operation to calculate the changes in cortisol level. RESULTS: The two groups of patients were comparable for preoperative SAI scores (>0.05); The patients in the sedation group appeared to have lower intraoprative SAI scores, but this difference was not statistically significant (=0.05). MBP, HR, and SpO at the time points from T to T and OAA/S, WLi, ANXi, CFi, and Pi at the time points from T to T were significantly lower in the sedation group (all < 0.05), and these parameters were not significantly different between the two groups at the other time points (all >0.05). The patient satisfaction scores were significantly higher in the sedation group (Z=2.07, < 0.05). Compared with the preoperative levels, serum cortisol level at the end of the operation was increased in the sedation group but lowered in the control group, and the variations of serum cortisol level differed significantly between the two groups (=4.75, < 0.01). CONCLUSIONS Intraoperative propofol sedation can alleviate the patients' anxiety, improve the comfort level, and lessen physiological stress during surgeries under epidural anesthesia.
Anesthesia, Epidural ; Blood Pressure ; drug effects ; Conscious Sedation ; Heart Rate ; drug effects ; Humans ; Hypnotics and Sedatives ; administration & dosage ; pharmacology ; Ileostomy ; Propofol ; administration & dosage ; pharmacology ; Stress, Psychological ; drug therapy ; Visual Analog Scale

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*

Two new sesquiterpenes, trivially named ricinusoids A (1) and ricinusoids B (2), were isolated from ethyl acetate fraction of Ricinus communis. The structures of new compounds were elucidated by detailed spectroscopic techniques, including 1D- and 2D-NMR, UV, IR spectroscopy, and mass spectrometry. The compounds (1-2) were also assessed for in-vivo sedative and analgesic like effects in open field and acetic acid induced writhing tests respectively at 5, 10, and 20 mg·kg i.p. Pretreatment of both test compounds caused significant (P ≤ 0.05) reduction in locomotive activity like sedative agents and abdominal constrictions like analgesics. Both compounds (1-2) possessed marked sedative and antinociceptive effects in animal models.
Analgesics ; administration & dosage ; chemistry ; isolation & purification ; Animals ; Humans ; Hypnotics and Sedatives ; administration & dosage ; chemistry ; isolation & purification ; Locomotion ; drug effects ; Male ; Mice ; Mice, Inbred BALB C ; Molecular Structure ; Pain ; drug therapy ; physiopathology ; Plant Extracts ; administration & dosage ; chemistry ; isolation & purification ; Plant Leaves ; chemistry ; Ricinus ; chemistry ; Sesquiterpenes ; administration & dosage ; chemistry ; isolation & purification

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

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

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

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