Efficacy of intratracheal dexmedetomidine on recovery from general anaesthesia in paediatric patients undergoing lower abdominal surgeries: A randomised controlled trial.

BACKGROUND: This study investigated the effectiveness of intratracheal dexmedetomidine in reducing untoward laryngeal responses in paediatrics undergoing lower abdominal surgeries. METHODS: This trial included 60 patients divided into two groups scheduled for lower abdominal surgeries. Group D were given intratracheal dexmedetomidine at a dosage of 0.5mg/kg, while Group C received intratracheal saline (0.9%). The cough severity score, the Paediatric Objective Pain Scale for pain assessment, awareness, extubation, emergence agitation score, Ramsay sedation score and adverse effects were recorded. RESULTS: There was a significant difference in the incidence of coughing severity between Groups D and C both at extubation and after five minutes of extubation (p < 0.001). The median scores of the Paediatric Objective Pain Scales and the median agitation scales of Group D were significantly lower over the first four hours (p < 0.050). The mean time to first request rescue analgesia was significantly longer in the D group than in the control group (p < 0.001). The mean total consumption of rescue analgesia in the first 24 hours postoperatively was significantly lower in the dexmedetomidine group (p < 0.050). Awareness and extubation times were comparable in both groups, and none of the subjects reported any adverse effects. CONCLUSION: In the current study, lower abdominal surgery patients who received intratracheal dexmedetomidine at a dose of 0.5mg/kg 30 minutes before the completion of the procedure experienced smooth extubation and balanced anaesthetic recovery.

Effect of intraoperative dexmedetomidine on recovery of gastrointestinal function after caesarean section undergoing spinal and epidural anesthesia: A randomized, double blind, placebo-controlled clinical trial.

OBJECTIVE: Gastrointestinal dysfunction after cesarean section negatively affects postoperative recovery. Dexmedetomidine has been shown to improve postoperative gastrointestinal function in patients undergoing lumbar spinal fusion surgery and laparoscopic gastrectomy, but its role in cesarean section has not been fully elucidated. The study aimed to investigate the effect of dexmedetomidine on gastrointestinal function after cesarean section. STUDY DESIGN: 220 pregnant women who underwent elective cesarean section were randomized into group D and group S. Group D patients received a loading dose of 0.5 µg/kg of dexmedetomidine for 10 mins followed by a maintenance dose of 0.5 µg/kg/h intravenously immediately after the umbilical cord was cut intraoperatively, whereas the other group (group S) received an equivalent quantity of normal saline as loading and maintenance dose IV by infusion pump. The primary outcome was time to first flatus after surgery (hours). Secondary outcomes included time to first feces and first bowel sounds (hours), incidence rates of postoperative gastrointestinal complications, and the length of postoperative hospital stay (days). RESULTS: Modified intention-to-treat analysis showed that patients in Group D had a significantly shorter time to first flatus (21 [16 to 28.25] vs. 25 [18 to 32.25] h; P = 0.014), time to first feces (45.5 [35.75 to 55.25] vs. 53 [40 to 60] h; P = 0.019), and time to first bowel sounds (P = 0.010), a lower incidence of abdominal distension (21[20.6 %] vs. 36[34.3 %], P = 0.027), shorter length of postoperative hospital stay (P = 0.010) compared to patients in Group S. CONCLUSION: Intraoperative dexmedetomidine infusion reduces the time to first flatus, the incidence of abdominal distension, and shortens the length of hospital stay, promoting gastrointestinal function after cesarean section.

Dexmedetomidine as an Adjunct to Propofol in Patients Undergoing Elective Endoscopic Retrograde Cholangio-Pancreaticography - A Double-blind Randomized Controlled Study.

Background: Propofol is the drug of choice for procedural sedation. The addition of α2 agonist dexmedetomidine may improve the safety profile of the procedure by providing stable hemodynamics, better sedation quality, and decreasing the side effects of each drug during elective endoscopic retrograde cholangio-pancreaticography (ERCP). Materials and Methods: Eighty patients aged between 18 and 60 years were distributed randomly into two groups. The dexmedetomidine + propofol group (group DP) received an injection of dexmedetomidine at the dose of 1 mcg/kg in 100 mLsaline, and the propofol group (group P) received plain 100 mL normal saline over 10 min. Subsequently, both groups received a bolus dose of injection propofol 1 mg/kg as sedation, and a modified observer's assessment of alertness/sedation score (MOASS) score was assessed, followed by infusion at the rate of 50 mcg/kg/min during the procedure. A rescue bolus dose (20 mg) of propofol was administered when the patient showed signs of inadequate sedation or analgesia in both groups. Cardiovascular and respiratory parameters were recorded every 10 min throughout the procedure. Post-procedure modified Aldrete score was evaluated for 30 min, and the endoscopist's score was noted at the end of the procedure. Results: There was a significant difference (P = 0.001) in the additional number of rescue doses of propofol administered in group DP (3.47 ± 0.77) as compared to group P (8.78 ± 1.11). The total dose of propofol was lower in group DP (316.59 ± 43.29 mg) than in group P (443 ± 41.1 mg) with P value = 0.001. Statistically significant differences in the hemodynamic values were observed in group DP during infusion (P value < 0.05) of dexmedetomidine and throughout the procedure (P < 0.05) when compared with group P. Endoscopists graded the satisfaction score as very high (3.477 ± 0.77) in group DP. Conclusion: The addition of dexmedetomidine to propofol during ERCP provided better and safer sedation.

Optimum programmed intermittent epidural bolus interval time of ropivacaine 0.0625% with dexmedetomidine 0.4 µg/ml at a fixed volume of 10 mL: a randomized controlled trial.

Background: The aim of our study was to administer adequate local anesthetic in programmed intermittent epidural bolus (PIEB) to avoid breakthrough pain and decrease the use of manual and PCEA boluses. We, therefore, conducted this study to determine the effective PIEB interval time between boluses of ropivacaine 0.0625% with dexmedetomidine 0.4 µg/ml at a fixed volume of 10 mL in 90% of subjects (EI90), without the use of patient-controlled epidural analgesia (PCEA). Methods: A total of 80 subjects were included in the final statistical analysis from 23 August 2022 to 22 November 2022. The subjects were randomly assigned to one of four different PIEB time intervals: 40, 50, 60, and 70 min (groups 40, 50, 60, and 70), respectively. The primary outcome was the effective epidural labor analgesia, defined as no use of PCEA bolus or a manual bolus until the end of the first stage of labor or within 6 hours after loading dose administration. The PIEB EI90 (95% CI) between boluses of ropivacaine 0.0625% with dexmedetomidine 0.4 µg/ml at a fixed volume of 10 mL was estimated using probit regression. Results: The effective PIEB interval time between boluses of ropivacaine 0.0625% with dexmedetomidine 0.4 µg/ml at a fixed volume of 10 mL in 90% of subjects without the use of PCEA was 45.4 (35.5-50.5) minutes using probit regression. No statistical differences were found in the proportion of subjects with Bromage score > 0, hypotension, pruritus, nausea, and vomiting between groups. However, the highest sensory block (pinprick) in the 40-min group was significantly higher than that in the other groups. Conclusion: The estimated value for EI90 for PIEB between boluses of ropivacaine 0.0625% with dexmedetomidine 0.4 µg/ml at a fixed volume of 10 mL using probit regression was 45.4 (35.5-50.5) minutes. Furthermore, future studies are warranted to be established to determine the optimal parameters for different regimens in clinical practice.

Effect of Dexmedetomidine on Incidence of Hypertension Following Repair of Coarctation of the Aorta.

OBJECTIVE: Recent literature suggests a potential role for dexmedetomidine in reducing the incidence and severity of hypertension following repair of coarctation of the aorta (CoA). The primary aim of this study was to assess the association between dexmedetomidine use and the incidence of hypertension following repair of CoA in pediatric patients. METHODS: This was a single-center, retrospective cohort study in patients younger than 19 years who underwent surgical repair of CoA between January 1, 2016, and September 30, 2021. Patients were divided into 2 groups: dexmedetomidine initiation within the first 3 hours after surgery or no dexmedetomidine. The primary outcome was incidence of hypertension within the first 4 to 24 hours after repair. Secondary outcomes included the incidence of hypotension and bradycardia. RESULTS: A total of 80 patients were included, 25 (31.25%) received dexmedetomidine. Median age at the time of procedure was 26 days (IQR, 13-241) in the dexmedetomidine group and 14 days (IQR, 8-53) in the no dexmedetomidine group (p = 0.014). The primary outcome of hypertension was met in 7 patients (28%) in the dexmedetomidine group and 12 patients (21.8%) in the no dexmedetomidine group, p = 0.547. The only variable found to be associated with the incidence of hypertension was age greater than 30 days at the time of procedure. More patients who received dexmedetomidine experienced bradycardia. There was no difference in the incidence of hypotension. CONCLUSIONS: There was no association between the use of dexmedetomidine and the incidence of -hypertension following repair of CoA in pediatric patients.

Synergistic interaction of guanfacine or dexmedetomidine coadministered with lidocaine for cutaneous analgesia in rats.

BACKGROUND: This study examined the cutaneous analgesic effects of lidocaine co-injected with guanfacine and its comparison with dexmedetomidine. METHODS: Cutaneous analgesic effects are quantified through the blocking effects of the cutaneous trunci muscle reflex against skin pinpricks in rats. The dose-response curves of guanfacine, dexmedetomidine, and lidocaine were constructed and drug-drug interactions were analyzed by the ED50 isobologram. RESULTS: Subcutaneous injections of guanfacine, dexmedetomidine, and lidocaine produced dose-dependently nociceptive/sensory blockade. On the ED50 (50% effective dose) basis, the potency rankings of the drug are dexmedetomidine (0.09 [0.08-0.11] µmol/kg) > guanfacine (3.98 [2.96-5.34] µmol/kg) > lidocaine (25.40 [23.51-27.44] µmol/kg) (p < 0.01). On their equipotent doses (ED25, ED50, and ED75), the duration of sensory blockade induced by guanfacine or dexmedetomidine was longer than lidocaine's (p < 0.01). Both guanfacine and dexmedetomidine showed synergistic effects with lidocaine. CONCLUSIONS: We showed that guanfacine elicits dose-dependent cutaneous analgesia when administered subcutaneously. Lidocaine is less potent than guanfacine or dexmedetomidine. Both guanfacine and dexmedetomidine enhance the potency and duration of lidocaine. Better synergistic responses we are getting with guanfacine plus lidocaine.

Dexmedetomidine promotes colorectal cancer progression via Piwil2 signaling.

PURPOSE: α2-adrenoceptor agonist dexmedetomidine (DEX) has been reported to promote tumorigenesis. Stem-cell protein Piwil2 is associated with cancer progression. Whether Piwil2 plays a role in tumor-promoting effects of DEX is unknown. METHODS: We examined the expression of Piwil2 in human colorectal cancer (CRC) cell lines with/without DEX treatment. We also studied the roles of Piwil2 in proliferation, invasion, migration, as well as expressions of epithelial-mesenchymal transition (EMT)-related proteins in DEX-treated in vitro and in vivo CRC models. And the experiments with genetic and pharmacological treatments were conducted to investigate the underlying molecular mechanism. RESULTS: RNA-sequencing (RNA-seq) analysis found Piwil2 is one of most upregulated genes upon DEX treatment in CRC cells. Furthermore, Piwil2 protein levels significantly increased in DEX-treated CRC cancer cells, which promoted proliferation, invasion, and migration in both CRC cell lines and human tumor xenografts model. Mechanistically, DEX increased nuclear factor E2-related factor 2 (Nrf2) expression, which enhanced Piwil2 transcription via binding to its promoter. Furthermore, in vitro experiments with Piwil2 knockdown or Siah2 inhibition indicated that DEX promoted EMT process and tumorigenesis through Siah2/PHD3/HIF1α pathway. The experiments with another α2-adrenoceptor agonist Brimonidine and antagonists yohimbine and atipamezole also suggested the role of Piwil2 signaling in tumor-promoting effects via an α2 adrenoceptor-dependent manner. CONCLUSION: DEX promotes CRC progression may via activating α2 adrenoceptor-dependent Nrf2/Piwil2/Siah2 pathway and thus EMT process. Our work provides a novel insight into the mechanism underlying tumor-promoting effects of α2-adrenoceptor agonists.

Multimodal blood loss prevention bundle for endoscopic resection of juvenile nasopharyngeal angiofibroma: A case series.

Surgery for excision of juvenile nasopharyngeal angiofibroma (JNA) carries the possibility of massive life-threatening haemorrhage. Anaesthetic management aims to maintain haemodynamic stability and reduce blood loss. This case series describes the application of the bundled approach as a multimodal blood loss prevention bundle (MBLPB). Twenty patients underwent 23 surgeries with MBLPB. The blood loss and the number of units of blood transfused were recorded. The surgeon satisfaction score was assessed. The median [interquartile range (IQR)] estimated blood loss was 1300 (650-2350) ml. Patients with tumours in stages I and II had a median (IQR) blood loss of 550 (270-750) ml compared to patients with higher grades of tumours (stages III, IV) with a median (IQR) blood loss of 2100 (1300-2500) ml. Median (IQR) units of packed red cells transfused was 1 (0-3). The surgeon's satisfaction score was high when MBLPB was applied for JNA. However, it does not appear to reduce blood loss markedly.

Bispectral index-guided comparison of dexmedetomidine and fentanyl as an adjuvant with propofol to achieve an adequate depth for endotracheal intubation - A double-blind randomised controlled trial.

Background and Aims: Laryngoscopy and tracheal intubation require an adequate depth of anaesthesia. The study's primary objective was to compare the time needed to achieve the bispectral index (BIS)-guided adequate depth of anaesthesia for endotracheal intubation using fentanyl and dexmedetomidine. Methods: After institutional ethics committee clearance and written informed consent, this randomised study was conducted on 140 patients of either gender between 18 and 60 years who were scheduled for elective surgeries under general anaesthesia. Patients were randomised to intravenous dexmedetomidine 1 µg/kg (Group D) or fentanyl 2 µg/kg (Group F). The drugs were given as an intravenous infusion over 10 min before induction of anaesthesia. The primary outcome was the time required to achieve BIS 50. Normally distributed variables were compared using Student's t-test, and non-normally distributed variables were compared using the Mann-Whitney U test. Qualitative data were analysed using Chi-square/Fisher's exact test. A P value <0.05 was considered significant. Results: The time to achieve BIS 50 was lesser in Group F, 1546 (27) as compared to Group D, 1558 (11) s [mean difference (95% confidence interval (CI) 12[5.11, 18.89]), P < 0.001]. Haemodynamic parameters were comparable at all time points between both the groups, except heart rate, which was significantly lower. Propofol consumption was significantly less in group D than in group F [125.9 (25.36) versus 157.3 (42.80) mg, respectively, mean difference (95% CI) 31.4 (-44.16 to -20.63) P < 0.001)]. Conclusion: Dexmedetomidine achieves BIS 50 faster and has a propofol-sparing effect as compared to fentanyl.

The Safety and Efficacy of Remimazolam Compared to Dexmedetomidine for Awake Tracheal Intubation by Flexible Bronchoscopy: A Randomized, Double-Blind, Controlled Trial.

Background: Remimazolam is a novel ultra-short-acting benzodiazepine sedative that has the potential to be an alternative for procedural sedation due to its rapid sedation and recovery, no accumulation effect, stable hemodynamics, minimal respiratory depression, anterograde amnesia effect, and specific antagonist. Here, we aimed to compare the safety and efficacy of remimazolam with dexmedetomidine for awake tracheal intubation by flexible bronchoscopy (ATI-FB). Methods: Ninety patients scheduled for ATI-FB were randomly divided into three groups, each consisting of 30 cases: dexmedetomidine 0.6 µg/kg + sufentanil (group DS), remimazolam 0.073 mg/kg + sufentanil (group R1S), or remimazolam 0.093 mg/kg + sufentanil (group R2S). The primary outcome was the success rate of sedation. Secondary outcomes were MOAA/S scores, hemodynamic and respiratory parameters, intubation conditions, intubation time, tracheal intubation amnesia, and adverse events. Results: The success rates of sedation in groups R2S and DS were higher than that in group R1S (93.3%, 86.7%, respectively, vs 58.6%; P = 0.002), and intubation conditions were better than those in group R1S (P < 0.05). Group R2S had shorter intubation times than groups R1S and DS (P = 0.003), and a higher incidence of tracheal intubation amnesia than group DS (P = 0.006). No patient in the three groups developed hypoxemia or hypotension, and there were no significant differences in oligopnea, PetCO2, or bradycardia (P > 0.05). Conclusion: In conclusion, both DS and R2S had higher success rates of sedation, better intubation conditions, and minor respiratory depression, but R2S, with its shorter intubation time, higher incidence of anterograde amnesia, and ability to be antagonized by specific antagonists, may be a good alternative sedation regimen for patients undergoing ATI-FB.

Dexmedetomidine affects the NOX4/Nrf2 pathway to improve renal antioxidant capacity.

OBJECTIVES: The study aimed to investigate the protective effects of dexmedetomidine (DEX) on renal injury caused by acute stress in rats and explore the protective pathways of DEX on rat kidneys in terms of oxidative stress. METHODS: An acute restraint stress model was utilized, where rats were restrained for 3 hours after a 15-minute swim. Biochemical tests and histopathological sections were conducted to evaluate renal function, along with the measurement of oxidative stress and related pathway proteins. KEY FINDINGS: The open-field experiments validated the successful establishment of the acute stress model. Acute stress-induced renal injury led to increased NADPH oxidase 4 (NOX4) protein expression and decreased expression levels of nuclear transcription factor 2 (Nrf2), heme oxygenase-1 (HO-1), and NAD(P)H: quinone oxidoreductase 1 (NQO1). Following DEX treatment, there was a significant reduction in renal NOX4 expression. The DEX-treated group exhibited normalized renal biochemical results and less damage observed in pathological sections compared to the acute stress group. CONCLUSIONS: The findings suggest that DEX treatment during acute stress can impact the NOX4/Nrf2/HO-1/NQO1 signaling pathway and inhibit oxidative stress, thereby preventing acute stress-induced kidney injury. Additionally, DEX shows promise for clinical applications in stress syndromes.

Study of caudal ropivacaine with or without dexmedetomidine for postoperative analgesia in paediatric genitourinary infraumbilical surgery: a double-blinded randomized controlled trial.

Various studies have described the use of Dexmedetomidine with local anaesthetic drugs in caudal blocks for the management of postoperative pain in children. This study was designed to determine the analgesic effect of caudal Dexmedetomidine with Ropivacaine in paediatric genitourinary infraumbilical surgeries. Postoperative analgesic effects of caudal Ropivacaine with or without Dexmedetomidine in paediatric genitourinary infraumbilical were evaluated. This study was a prospective, interventional, comparative study conducted after ethical approval from the institute. Informed expressed consent was taken from each patient's guardians. The sample size was calculated to be 31 in each group. The two groups were randomly assigned and the intervention involved caudal epidural injection with either Ropivacaine combined with Dexmedetomidine or Ropivacaine with Normal Saline. Children receiving Ropivacaine with Dexmedetomidine had a significantly prolonged duration of analgesia compared to those receiving Ropivacaine alone (840.35 ± 149.97 vs. 412.90 ± 93.46 min, P < 0.001). Postoperative rFLACC scores were consistently lower in the Dexmedetomidine group, indicating better pain control (P < 0.05 at 6, 12, and 24 h). Total analgesic consumption was lower in the Dexmedetomidine group (500.67 ± 212.92 vs. 741.75 ± 268.06 mg, P < 0.01). No significant differences in adverse effects were observed between the groups. The addition of Dexmedetomidine to Ropivacaine in caudal epidural significantly prolongs analgesia, improves pain control, and reduces analgesic consumption in paediatric genitourinary infraumbilical surgeries.

Nicardipine constant rate infusion alleviates the cardiovascular effects of dexmedetomidine infusions without affecting the minimal alveolar concentration in sevoflurane-anesthetized dogs.

Two randomized crossover trials evaluated the effects of nicardipine constant rate infusion (CRI) on 1) the anesthetic potency of sevoflurane and 2) the ability to attenuate dexmedetomidine-induced cardiovascular depression in anesthetized dogs. First, six healthy Beagle dogs weighing 11.7 ± 0.9 kg were allocated to one of three treatments that administered a CRI of carrier (saline) or dexmedetomidine 0.5 or 3.0 µg/kg/h following a loading dose. The minimum alveolar concentration (MAC) of sevoflurane was determined utilizing electric stimuli before and after the loading dose of nicardipine (20 µg/kg intravenously for 10 min), followed by CRI at 40 µg/kg/h with 60 min of equilibration. Subsequently, cardiovascular and blood gas variables were evaluated in another trial under sevoflurane anesthesia at the individual 1.5 MAC. After baseline measurements, the dogs were assigned to two treatments (dexmedetomidine CRI at 0.5 or 3.0 µg/kg/h following a loading dose) with sevoflurane doses adjusted to 1.5 times of MAC equivalent, and the measurements were repeated every 15 min for 120 min. After 60 min, nicardipine CRI at 40 µg/kg/h with a loading dose was added to the dexmedetomidine CRI. Dexmedetomidine infusions significantly decreased the sevoflurane MAC but nicardipine did not significantly alter the MAC either with or without dexmedetomidine CRI in dogs. Dexmedetomidine dose-dependently decreased the cardiac index and increased the systemic vascular resistance index; these effects were fully counteracted by concomitant nicardipine CRI. Nicardipine CRI can be useful for controlling the cardiovascular depression elicited by dexmedetomidine in anesthetized dogs without affecting the anesthetic potency of sevoflurane.

Continuous Superior Trunk Block versus Single-Shot Superior Trunk Block with Intravenous Dexmedetomidine for Postoperative Analgesia in Arthroscopic Shoulder Surgery: A Prospective Randomized Controlled Trial.

Background/Objectives: Intravenous dexmedetomidine (DEX) can increase the analgesia duration of peripheral nerve block; however, its effect in combination with superior trunk block (STB) remains unclear. We examined whether combining single-shot STB (SSTB) with intravenous DEX would provide noninferior postoperative analgesia comparable to that provided by continuous STB (CSTB). Methods: Ninety-two patients scheduled for elective arthroscopic rotator cuff repair were enrolled in this prospective randomized trial. Patients were randomly assigned to the CSTB or SSTB + DEX group. Postoperatively, each CSTB group patient received 15 mL of 0.5% ropivacaine and a continuous 0.2% ropivacaine infusion. Each SSTB group patient received a 15 mL postoperative bolus injection of 0.5% ropivacaine. DEX was administered at 2 mcg/kg for 30 min post anesthesia, then maintained at 0.5 mcg/kg/h till surgery ended. Pain scores were investigated every 12 h for 48 h post operation, with evaluation of rebound pain incidence and opioid consumption. Results: The SSTB + DEX group had significantly higher median pain scores at 12 h post operation (resting pain, 8.0 vs. 3.0; movement pain, 8.0 vs. 5.0) and a higher incidence of rebound pain (56% vs. 20%) than the CSTB group. However, no significant between-group differences were observed in pain scores postoperatively at 24, 36, or 48 h. The CSTB group required less opioids and fewer rescue analgesics within 12-24 h post operation than the SSTB + DEX group. Conclusions: Compared with CSTB, SSTB + DEX required additional adjuvant or multimodal analgesics to reduce the risk and intensity of postoperative rebound pain in patients who underwent arthroscopic rotator cuff repair.

Mechanism of dexmedetomidine protection against cisplatin induced acute kidney injury in rats.

OBJECTIVE: This study explored the molecular mechanisms by which dexmedetomidine (Dex) alleviates cisplatin (CP)-induced acute kidney injury (AKI) in rats. METHODS: CP-induced AKI models were established, and Dex was intraperitoneally injected at different concentrations into rats in the model groups. Subsequently, rats were assigned to the control, CP, CP + Dex 10 µg/kg, and CP + Dex 25 µg/kg groups. After weighing the kidneys of the rats, the kidney arterial resistive index was calculated, and CP-induced AKI was evaluated. In addition, four serum biochemical indices were measured: histopathological damage in rat kidneys was detected; levels of inflammatory factors, interleukin (IL)-1ß, IL-18, IL-6, and tumor necrosis factor alpha, in kidney tissue homogenate of rats were assessed through enzyme-linked immunosorbent assay (ELISA); and levels of NLRP-3, caspase-1, cleaved caspase-1, gasdermin D (GSDMD), and GSDMD-N in kidney tissues of rats were determined via western blotting. RESULTS: Dex treatment reduced nephromegaly and serum clinical marker upregulation caused by CP-induced AKI. In addition, hematoxylin and eosin staining revealed that Dex treatment relieved CP-induced kidney tissue injury in AKI rats. ELISA analyses demonstrated that Dex treatment reduced the upregulated levels of proinflammatory cytokines in the kidney tissue of AKI rats induced by CP, thereby alleviating kidney tissue injury. Western blotting indicated that Dex alleviated CP-induced AKI by inhibiting pyroptosis mediated by NLRP-3 and caspase-1. CONCLUSION: Dex protected rats from CP-induced AKI, and the mechanism may be related to NLRP-3/Caspase-1-mediated pyroptosis.

Daytime dexmedetomidine sedation with closed-loop acoustic stimulation alters slow wave sleep homeostasis in healthy adults.

Background: The alpha-2 adrenergic agonist dexmedetomidine induces EEG patterns resembling those of non-rapid eye movement (NREM) sleep. Fulfilment of slow wave sleep (SWS) homeostatic needs would address the assumption that dexmedetomidine induces functional biomimetic sleep states. Methods: In-home sleep EEG recordings were obtained from 13 healthy participants before and after dexmedetomidine sedation. Dexmedetomidine target-controlled infusions and closed-loop acoustic stimulation were implemented to induce and enhance EEG slow waves, respectively. EEG recordings during sedation and sleep were staged using modified American Academy of Sleep Medicine criteria. Slow wave activity (EEG power from 0.5 to 4 Hz) was computed for NREM stage 2 (N2) and NREM stage 3 (N3/SWS) epochs, with the aggregate partitioned into quintiles by time. The first slow wave activity quintile served as a surrogate for slow wave pressure, and the difference between the first and fifth quintiles as a measure of slow wave pressure dissipation. Results: Compared with pre-sedation sleep, post-sedation sleep showed reduced N3 duration (mean difference of -17.1 min, 95% confidence interval -30.0 to -8.2, P=0.015). Dissipation of slow wave pressure was reduced (P=0.02). Changes in combined durations of N2 and N3 between pre- and post-sedation sleep correlated with total dexmedetomidine dose, (r=-0.61, P=0.03). Conclusions: Daytime dexmedetomidine sedation and closed-loop acoustic stimulation targeting EEG slow waves reduced N3/SWS duration and measures of slow wave pressure dissipation on the post-sedation night in healthy young adults. Thus, the paired intervention induces sleep-like states that fulfil certain homeostatic NREM sleep needs in healthy young adults. Clinical trial registration: ClinicalTrials.gov NCT04206059.

Co-administration of naloxone and dexmedetomidine to simultaneously reverse acute effects of fentanyl and methamphetamine in rats.

BACKGROUND: The incidence of combination methamphetamine (METH)-opioid overdose has substantially increased in recent years. While agitation is uncommon after the naloxone (NLX) reversal of opioids, it is a major clinical concern in acute METH intoxication and can be physiologically antagonized by opioid-induced sedation. This study aimed to perform initial preclinical analysis of the safety and efficacy of dexmedetomidine (DEXMED) co-administered with NLX to attenuate METH-induced locomotor activity, as a rat model of agitation, after the reversal of fentanyl (FENT)-induced sedation. METHODS: Male Sprague Dawley rats were administered subcutaneous (SC) 0.1mg/kg FENT ± 1mg/kg METH. Fifteen min later, SC 0.1mg/kg NLX ± an increasing (0, 0.032, 0.056, and 0.1mg/kg) DEXMED dose was administered prior to the measurement of locomotor activity. After a washout period, the FENT ± METH and NLX ± DEXMED administration with the highest dose of DEXMED was administered for measurement of blood oxygen saturation and heart rate. RESULTS: After the NLX reversal of FENT-induced sedation, adjunct DEXMED substantially and significantly reduced METH-induced locomotor activity (p<0.05) at all doses tested. While the addition of DEXMED did not significantly reduce blood oxygenation in METH treated rats, it did so in the absence of METH. Also, DEXMED significantly reduced heart rate compared to non-DEXMED treated groups and resulted in further significant reductions in the animals not exposed to METH (p<0.05). CONCLUSIONS: These data provide preclinical evidence that DEXMED may be a safe and effective chemical restraint for METH-induced agitation after NLX opioid reversal.

The Median Effective Dose of Dexmedetomidine for the Inhibition of Emergence Delirium in Preschool Children Undergoing Tonsillectomy and/or Adenoidectomy: A Retrospective Dose-response Trial.

The incidence of emergence delirium (ED) is higher in preschool children undergoing tonsillectomy and/or adenoidectomy. The purpose of this study was to determine the median effective dose (ED50) of dexmedetomidine (DEX) for the inhibition of ED in preschool children by using probit regression analysis. A total of 140 anesthesia records were retrieved and divided into seven groups based on the infusion rate of DEX: .2, .25, .3, .35, .4, .45, and .5 µg·kg-1·h-1. The Pediatric Anesthesia Emergence Delirium Scale (PAEDS) was used to assess ED in preschool children, and ED was defined as a PAEDS score ≥ 10. Probit regression analysis revealed that the ED50 and ED95 of DEX were .31 µg·kg-1·h-1 (95% CI: .29-.35) and .48 µg·kg-1·h-1 (95% CI: .44-.56), respectively. Probit(p) = -2.84 + 9.28 × ln (Dose), (χ2 = 1.925, P = .859). The PAEDS score was significantly increased in the ED group, and the rate of bradycardia was significantly decreased in the ED group compared with the without ED group (27.3% vs 54.1%, P = .02). DEX can effectively inhibit the ED in preschool children undergoing tonsillectomy and/or adenoidectomy, however, bradycardia was the main complication.

Comparative evaluation of nebulized versus intravenous dexmedetomidine on intubating conditions during awake fiberoptic nasotracheal intubation.

BACKGROUND: There is a search for an ideal agent to facilitate awake fiberoptic intubation (AFOI). Dexmedetomidine is a selective α2 agonist which can be administered through intravenous, intramuscular, buccal, intranasal & inhalational routes. It provides good intubation conditions without oxygen desaturation but may cause hypotension and bradycardia when administered intravenously. Hence, alternative routes of administering dexmedetomidine which may improve its safety profile are worth exploring. METHODS: In this randomised, controlled, double-blind trial, 46 ASA I/II adult participants scheduled for elective ENT surgery were randomly allocated to Group ND (Nebulised Dexmedetomidine) (n = 23) to receive nebulisation with dexmedetomidine 1µg.kg-1 and Group ID (Intravenous Dexmedetomidine) (n = 23) to receive intravenous dexmedetomidine 1µg.kg-1 before AFOI. All the patients received injection midazolam 1 mg i.v. as premedication before anaesthesia was initiated. The primary outcome was the cough score. The secondary outcomes were the RSS, SAYGO boluses, post-intubation score, hemodynamic parameters, recall of the procedure, patient satisfaction score and any side effects. RESULTS: The cough score was significantly lower in nebulized group (2.43 ± 0.992 vs 3.52 ± 1.082) with p = 0.001. RSS(3.30 ± 0.926 vs 4.22 ± 1.126; p = 0.004), number of SAYGO boluses required (2.74 ± 0.864 vs 3.57 ± 1.161; p = 0.009) & the post intubation score (1.48 ± 0.593 vs 2.17 ± 0.778; p = 0.001) were also significantly lower in nebulized group. CONCLUSIONS: Nebulisation with dexmedetomidine results in desirable degree of sedation and better tolerance of the procedure with adequate attenuation of the haemodynamic responses to intubation.

Predictors for Dexmedetomidine Requirement for Sedation under Regional Anesthesia.

(1) Background: This prospective observational study aimed to investigate the predictors affecting DMT requirements for sedation during regional anesthesia. (2) Method: A total of 108 patients who received regional anesthesia with intravenous DMT administration for orthopedic upper- or lower-extremity surgery were enrolled. Following successful regional anesthesia, DMT was administered at a rate of 4 µg/kg/h until reaching loss of consciousness (LOC). The administered dose of DMT per body weight until LOC (DMTLOC; µg/kg) was evaluated. The infusion was maintained at a rate of 0.2-0.7 µg/kg/h during the surgery. At the end of surgery, the elapsed time to a BIS value of 90 (TBIS90; s) was recorded. Linear regression models were used to identify potential predictors of DMTLOC and TBIS90. (3) Results: One hundred patients were analyzed. There were negative relationships between DMTLOC and age (r = -0.297, p = 0.003) and DMTLOC and body mass index (BMI) (r = -0.425, p < 0.001), respectively. Multiple linear regression models revealed that both increasing age and BMI were significantly related to DMTLOC (r2 = 0.259, p < 0.001), but those variables showed no association with TBIS90. (4) Conclusions: The results of this study suggest that initial loading of DMT should be carefully titrated to minimize risk in elderly and obese surgical populations.