Explore the vast range of titles available.

Dexmedetomidine (Dexdor ® ) is a highly selective α 2 -adrenoceptor agonist. It has sedative, analgesic and opioid-sparing effects and is suitable for short- and longer-term sedation in an intensive care setting. In the randomized, double-blind, multicentre MIDEX and PRODEX trials, longer-term sedation with dexmedetomidine was noninferior to midazolam and propofol in terms of time spent at the target sedation range, as well as being associated with a shorter time to extubation than midazolam or propofol, and a shorter duration of mechanical ventilation than midazolam. Patients receiving dexmedetomidine were also easier to rouse, more co-operative and better able to communicate than patients receiving midazolam or propofol. Dexmedetomidine had beneficial effects on delirium in some randomized, controlled trials (e.g. patients receiving dexmedetomidine were less likely to experience delirium than patients receiving midazolam, propofol or remifentanil and had more delirium- and coma-free days than patients receiving lorazepam). Intravenous dexmedetomidine had an acceptable tolerability profile; hypotension, hypertension and bradycardia were the most commonly reported adverse reactions. In conclusion, dexmedetomidine is an important option for sedation in the intensive care setting.

The study examined the effect of [[alpha].sub.2]-adrenoreceptor ([[alpha].sub.2]-AR) activation against the background of preliminary blockage of [I.sub.f] on the performance of Langerndorff-isolated rat heart. Stimulation of [[alpha].sub.2]-AR in isolated rat hearts against the background of ZD7288 in concentrations of [10.sup.-9] M and 3x[10.sup.-5] M changed the negative dynamics of myocardial inotropy to positive (by 25 and 38%; p<0.05). Activation of [[alpha].sub.2]-AR produced opposite effects on HR. [I.sub.f] blockade abolished tachycardia caused by activation of [[alpha].sub.2]-AR; HR deceleration in response to [[alpha].sub.2]-AR agonist against the background of [I.sub.f] blocker in a concentration [10.sup.-9] M was 41% (p<0.05). We observed negative dynamics of coronary flow (by 38%; p<0.05) in isolated adult rat hearts after application of [[alpha].sub.2]-AR agonist against the background of [I.sub.f] blockade ([10.sup.-9] M). Key Words: [alpha]2-adrenergic receptors; [I.sub.f]; isolated heart; rat

Background In this study, we aimed to compare the sedative effects, pharmacokinetics (PKs), and safety of dexmedetomidine (DEX) administered using a two-phase flow atomization device with those of conventional intranasal drop-based administration in healthy volunteers. Methods This prospective, parallel, double-blind study compared the PK and pharmacodynamic (PD) profiles of DEX administered via conventional intranasal drop (Group C) or two-phase flow atomization (Group E). Twenty-two healthy adult volunteers were enrolled and randomly assigned to the two groups using a computer-generated randomization sequence. Each participant received DEX at a dose of 2 µg/kg. Sedation was assessed using the Ramsay Sedation Scale and the bispectral index, and PK analysis was performed on blood samples collected at multiple time points. Results The two-phase flow atomization group exhibited a significantly faster onset of sedation than the conventional intranasal drop-based administration group and a longer duration of sedation. Compared with Group C, Group E presented an increasing trend in the maximum plasma concentration and in the area under the concentration‒time curve from time zero to the last time point (AUC0t). We found no significant differences in other PK parameters between the two groups, with all P -values > 0.05. The plasma concentrations were slightly higher in the two-phase flow atomization group after 30 min. The changes in systolic blood pressure and heart rate of both groups of volunteers were within 25% of the baseline values, with no adverse reactions such as hypotension or sinus bradycardia. Conclusions  The findings indicate that the two-phase flow atomization device offers faster onset and longer duration of sedation with DEX nasal administration, with a favorable safety profile in healthy volunteers (American Society of Anesthesiologists Physical Status Class 1) under specific conditions. Therefore, based on the sedation dynamics, we infer that this device may enhance drug deposition in the olfactory region of the nasal cavity, thereby enhancing the effects of the drug in the central nervous system through nose-to-brain delivery. This study provides new insights into the optimization of nasal drug delivery devices, particularly for pediatric patients and patients in clinical settings requiring rapid sedation. Trial registration This study was registered at ChiCTR.org.cn (registration number ChiCTR2400091480) on 29/10/2024.

Background Septic shock is associated with decreased vasopressor responsiveness. Experimental data suggest that central alpha2-agonists like dexmedetomidine (DEX) increase vasopressor responsiveness and reduce catecholamine requirements in septic shock. However, DEX may also cause hypotension and bradycardia. Thus, it remains unclear whether DEX is hemodynamically safe or helpful in this setting. Methods In this post hoc subgroup analysis of the Sedation Practice in Intensive Care Evaluation (SPICE III) trial, an international randomized trial comparing early sedation with dexmedetomidine to usual care in critically patients receiving mechanical ventilation, we studied patients with septic shock admitted to two tertiary ICUs in Australia and Switzerland. The primary outcome was vasopressor requirements in the first 48 h after randomization, expressed as noradrenaline equivalent dose (NEq [μg/kg/min] = noradrenaline + adrenaline + vasopressin/0.4). Results Between November 2013 and February 2018, 417 patients were recruited into the SPICE III trial at both sites. Eighty-three patients with septic shock were included in this subgroup analysis. Of these, 44 (53%) received DEX and 39 (47%) usual care. Vasopressor requirements in the first 48 h were similar between the two groups. Median NEq dose was 0.03 [0.01, 0.07] μg/kg/min in the DEX group and 0.04 [0.01, 0.16] μg/kg/min in the usual care group ( p  = 0.17). However, patients in the DEX group had a lower NEq/MAP ratio, indicating lower vasopressor requirements to maintain the target MAP. Moreover, on adjusted multivariable analysis, higher dexmedetomidine dose was associated with a lower NEq/MAP ratio. Conclusions In critically ill patients with septic shock, patients in the DEX group received similar vasopressor doses in the first 48 h compared to the usual care group. On multivariable adjusted analysis, dexmedetomidine appeared to be associated with lower vasopressor requirements to maintain the target MAP. Trial registration The SPICE III trial was registered at ClinicalTrials.gov ( NCT01728558 ).

Purpose The aim of this proof-of-concept study was to characterize the pharmacokinetics and pharmacodynamics of intranasal dexmedetomidine compared with its intravenous administration in a small number of healthy volunteers. Methods Single doses of 84 μg of dexmedetomidine were given once intravenously and once intranasally to seven healthy men. Plasma dexmedetomidine concentrations were measured for 10 h, and pharmacokinetic variables were calculated with standard noncompartmental methods. Heart rate, blood pressure, concentrations of adrenaline and noradrenaline in plasma, and central nervous system drug effects (with the Maddox wing, Bispectral Index, and three visual analog scales) were monitored to assess the pharmacological effects of dexmedetomidine. Results Six individuals were included in the analyses. Following intranasal administration, peak plasma concentrations of dexmedetomidine were reached in 38 (15–60) min and its absolute bioavailability was 65% (35–93%) (medians and ranges). Pharmacological effects were similar with both routes of administration, but their onset was more rapid after intravenous administration. Conclusions Dexmedetomidine is rather rapidly and efficiently absorbed after intranasal administration. Compared with intravenous administration, intranasal administration may be a feasible alternative in patients requiring light sedation.

Delirium is a postoperative complication that occurs frequently in patients older than 65 years, and presages adverse outcomes. We investigated whether prophylactic low-dose dexmedetomidine, a highly selective α2 adrenoceptor agonist, could safely decrease the incidence of delirium in elderly patients after non-cardiac surgery. We did this randomised, double-blind, placebo-controlled trial in two tertiary-care hospitals in Beijing, China. We enrolled patients aged 65 years or older, who were admitted to intensive care units after non-cardiac surgery, with informed consent. We used a computer-generated randomisation sequence (in a 1:1 ratio) to randomly assign patients to receive either intravenous dexmedetomidine (0·1 μg/kg per h, from intensive care unit admission on the day of surgery until 0800 h on postoperative day 1), or placebo (intravenous normal saline). Participants, care providers, and investigators were all masked to group assignment. The primary endpoint was the incidence of delirium, assessed twice daily with the Confusion Assessment Method for intensive care units during the first 7 postoperative days. Analyses were done by intention-to-treat and safety populations. This study is registered with Chinese Clinical Trial Registry, www.chictr.org.cn, number ChiCTR-TRC-10000802. Between Aug 17, 2011, and Nov 20, 2013, of 2016 patients assessed, 700 were randomly assigned to receive either placebo (n=350) or dexmedetomidine (n=350). The incidence of postoperative delirium was significantly lower in the dexmedetomidine group (32 [9%] of 350 patients) than in the placebo group (79 [23%] of 350 patients; odds ratio [OR] 0·35, 95% CI 0·22–0·54; p<0·0001). Regarding safety, the incidence of hypertension was higher with placebo (62 [18%] of 350 patients) than with dexmedetomidine (34 [10%] of 350 patients; 0·50, 0·32–0·78; p=0·002). Tachycardia was also higher in patients given placebo (48 [14%] of 350 patients) than in patients given dexmedetomidine (23 [7%] of 350 patients; 0·44, 0·26–0·75; p=0·002). Occurrence of hypotension and bradycardia did not differ between groups. For patients aged over 65 years who are admitted to the intensive care unit after non-cardiac surgery, prophylactic low-dose dexmedetomidine significantly decreases the occurrence of delirium during the first 7 days after surgery. The therapy is safe. Braun Anaesthesia Scientific Research Fund and Wu Jieping Medical Foundation, Beijing, China. Study drugs were manufactured and supplied by Jiangsu Hengrui Medicine Co, Ltd, Jiangsu, China.

Dexmedetomidine, a highly selective central α2-agonist, undergoes mainly biotransformation in the liver. The pharmacokinetics of dexmedetomidine were significantly affected by hepatic insufficiency. The clearance of dexmedetomidine in patients with severe hepatic failure decreased by 50% compared with controls. We tested the hypothesis that the pharmacokinetics of dexmedetomidine would be affected by obstructive jaundice. The prospective registration number of clinical trial is ChiCTR-IPR-15007572. 18 patients with obstructive jaundice and 12 non-jaundiced patient controls received dexmedetomidine, 1 μg/kg, over 10 min. Arterial blood samples were drawn before, during, and up to 5 h after the infusion. Plasma dexmedetomidine concentrations were determined by 1290 infinity high performance liquid chromatography coupled with 6470 tandem mass spectrometry. The relevant pharmacokinetic parameters were calculated by non-compartmental analysis using Phoenix WinNonlin 7.0. Plasma clearance of dexmedetomidine was decreased by 33.3% in the obstructive jaundice group as compared with the control group (0.0068±0.0017 vs. 0.0102±0.0033 L/kg/min; P = 0.002). Volume of distribution was decreased by 29.2% in the obstructive jaundice group as compared with the control group (1.43±0.58 vs. 2.02±0.84 L/kg; P = 0.041). This study demonstrates that the clearance and distribution volume of dexmedetomidine were decreased in patients with obstructive jaundice. It may be advisable to adjust the dose of dexmedetomidine in those patients.

Emergence agitation remains a problem that occurs in pediatric anesthesia. As cleft surgeries constitute one of the most common craniofacial surgeries encountered, majority of the children receive general anesthesia using high dose opioids and inhalation anesthetics and experience emergence agitation. Dexmedetomidine (DEX), an alpha-2 adrenoreceptor agonist possesses anxiolytic, sedative and analgetic properties and have been documented to reduce the incidence of postoperative agitation. Hence, this study aims to compare the incidence of emergence agitation between the use of intravenous DEX versus Sevoflurane (SEVO) anesthesia. This study selected one hundred twenty-one patients ages 3 months to 10 years with ASA 1 and 2 physical status scheduled to undergo elective cleft lip or cleft palate repair with general anesthesia. Before surgery, all patients were assessed preoperatively and subjects were divided into two groups using a computer-generated randomizer with 59 subjects selected as Dexmedetomidine group; and 62 subjects as Sevoflurane group. Extubation time, recovery time and emergence agitation scale were compared between the two groups. This study found no significant difference in the extubation time between DEX and SEVO group (p = 0.317). The recovery time or time to attain full consciousness was statistically longer in the DEX group: 60 minutes as compared to 52 minutes in the SEVO group (p = 0.007). Emergence agitation assessed using Cravero score found that subjects from DEX group had an average Cravero score of 2.5; while SEVO group had an average Cravero score of 3.9 (p = < 0.001). The incidence of agitation was significantly higher in the SEVO group compared to the DEX group: 82% as compared to 10% (p = < 0.001) with an OR of 40.955 CI 95% (14.098-118.9). Dexmedetomidine significantly reduces the incidence of emergence agitation without prolonging extubation time in pediatric patients undergoing cleft lip and cleft palate surgery.

•Dexmedetomidine is an α2-adrenoceptor agonist with sedative and anesthetic effects.•There are limited human studies on the effects of dexmedetomidine in septic shock.•In this clinical trial, we investigated the effect of dexmedetomidine on inflammatory factors, SOFA score, vital signs, and norepinephrine dose in septic shock patients.•Dexmedetomidine can regulate the inflammatory factors in patients with septic shock. Dexmedetomidine is a sedative-analgesic that is widely used in sepsis. However, its effect on septic shock remains unclear. This study aimed to investigate dexmedetomidine's effect on inflammatory biomarkers in septic shock. The present study was a randomized controlled clinical trial. Patients with inclusion criteria were randomly allocated into either the dexmedetomidine (n = 24) or morphine + midazolam group (n = 24). The primary outcome was changes in inflammatory factors, including IL-1, IL-6, TNF-α, ESR, and CRP. The serum levels of inflammatory factors were measured at baseline and the end of the intervention. Secondary outcomes included the change in norepinephrine dose, vital signs, and SOFA scores. Of the 48 subjects, 52.08% were male. After intervention, IL-1, IL-6, and TNF-α levels significantly differed between the 2 groups (p = 0.011 and p < 0.001 and p < 0.001, respectively). Heart rate and systolic blood pressure decreased over time, but the two groups had no significant difference (p-value > 0.05). In addition, there was no significant difference in norepinephrine dose and SOFA score between the 2 groups (p-value > 0.05). Sedation with dexmedetomidine can attenuate the inflammatory factors in septic shock. Also, dexmedetomidine did not worsen the hemodynamic parameters in septic shock patients.