Efficacy of dexmedetomidine as an adjuvant to local anesthetics in peribulbar block: a meta-analysis with trial-sequential analysis.

PURPOSE: To assess the role of dexmedetomidine as an adjuvant to local anesthetics (LA) in enhancing the duration and quality of peribulbar blocks for ophthalmic surgeries. DESIGN: Systematic review with meta-analysis and trial sequential analysis Methods: We systematically searched MEDLINE, Embase, and Cochrane for randomized controlled trials (RCTs) involving adult patients undergoing ophthalmic surgery under peribulbar block, comparing LA alone versus LA + dexmedetomidine. Risk ratios (RR) and mean differences (MD) with 95% confidence intervals (CI) were computed using a random effects model. Sensitivity and trial-sequential analyses (TSA) were performed to assess inconsistencies, weight type II and II errors, and estimate the required information size of the samples for all endpoints. RESULTS: Sixteen RCTs (1,220 patients) were included. Compared with LA alone, dexmedetomidine was associated with prolonged (1) motor block duration (MD 65.01 minutes, p<0.001) and (2) sensory block duration (MD 81.94 minutes, p<0.001); (3) reduced intraocular pressure (IOP) (MD -2.6 mmHg, p<0.001), and (4) decreased need for supplemental injections (RR 0.44, p=0.007). Additionally, dexmedetomidine showed (5) longer time to analgesic request (MD 97.15 minutes, p<0.001) and (6) increased surgeon satisfaction (RR 1.52, p=0.01). Sensitivity analyses and TSA were consistent across all endpoints, and the required information size was achieved for most endpoints, indicating that pooled analyses were reliable and sample sizes were sufficient. CONCLUSIONS: Compared with LA alone, dexmedetomidine significantly prolonged sensory and motor block duration and the time to the first analgesic request; decreased IOP and the need for supplemental injections, while increasing surgeon satisfaction.

Effects of perioperative dexmedetomidine on delayed graft function following renal transplant: a systematic review and meta-analysis.

BACKGROUND: Dexmedetomidine, a highly selective alpha-2 adrenoceptor agonist with sedative and analgesic effects, has been suggested in recent studies to possess renoprotective properties. Dexmedetomidine may reduce the incidence of delayed graft function and contribute to effective pain control post-renal transplantation. The primary objective of this systematic review was to assess whether dexmedetomidine decreases the occurrence of delayed graft function in renal transplant patients. METHODS: Databases including MEDLINE, EMBASE, and CENTRAL were comprehensively searched from their inception until March 2023. The inclusion criteria covered all Randomized Clinical Trials (RCTs) and observational studies comparing dexmedetomidine to control in adult patients undergoing renal transplant surgery. Exclusions comprised case series and case reports. RESULTS: Ten RCTs involving a total of 1358 patients met the eligibility criteria for data synthesis. Compared to the control group, the dexmedetomidine group demonstrated a significantly lower incidence of delayed graft function (OR = 0.71, 95% CI 0.52-0.97, p = 0.03, GRADE: Very low, I2 = 0%). Dexmedetomidine also significantly prolonged time to initiation of rescue analgesia (MD = 6.73, 95% CI 2.32-11.14, p = 0.003, GRADE: Very low, I2 = 93%) and reduced overall morphine consumption after renal transplant (MD = -5.43, 95% CI -7.95 to -2.91, p < 0.0001, GRADE: Very low, I2 = 0%). The dexmedetomidine group exhibited a significant decrease in heart rate (MD = -8.15, 95% CI -11.45 to -4.86, p < 0.00001, GRADE: Very low, I2 = 84%) and mean arterial pressure compared to the control group (MD = -6.66, 95% CI -11.27 to -2.04, p = 0.005, GRADE: Very low, I2 = 87%). CONCLUSIONS: This meta-analysis suggests that dexmedetomidine may potentially reduce the incidence of delayed graft function and offers a superior analgesia profile as compared to control in adults undergoing renal transplants. However, the high degree of heterogeneity and inadequate sample size underscore the need for future adequately powered trials to confirm these findings.

Combining melatonin with dexmedetomidine improves anesthesia in rats.

Melatonin (ML) and dexmedetomidine (DM) are used separately as anesthetic premedication or as an anesthetic in humans and laboratory animals. In this study, we aimed to investigate the anesthetic properties of both drugs combined. The anesthetic effects of several combinations of ML (50 and 100 mg/kg) and DM (50 and 100 µg/kg) were evaluated in rats by observing behavioral manifestations and recording the duration and depth of anesthesia. Five anesthetic intervals were established according to the loss and recovery of reflexes. While each individual drug did not induce an appropriate anesthetic effect at the tested doses, ML50 + DM100, ML100 + DM50 and ML100 + DM100 combinations resulted in surgical anesthesia intervals of 60 to 360 min. Together, our results point that the use of ML allows to decrease the dose of DM, reducing the unwanted anesthetic effects of this α2-agonist.

Comparison of intranasal dexmedetomidine versus oral midazolam for premedication in pediatric patients: an updated meta-analysis with trial-sequential analysis.

BACKGROUND: Midazolam is routinely used as preanesthetic medication in pediatric patients. Recently, dexmedetomidine has emerged as an alternative as a premedicant. We aimed to add more evidence about the efficacy and safety of two common routes of administration for pediatric premedication: oral midazolam versus intranasal dexmedetomidine. METHODS: We systematically searched Randomized Controlled Trials (RCTs) involving patients ≤ 18 years old undergoing preanesthetic medication and comparing intranasal dexmedetomidine with oral midazolam. Risk Ratio (RR) and Mean Difference (MD) with 95% Confidence Intervals (95% CI) were computed using a random effects model. Trial-sequential analyses were performed to assess inconsistency. RESULTS: Sixteen RCTs (1,239 patients) were included. Mean age was 5.5 years old, and most procedures were elective. There was no difference in satisfactory induction or mask acceptance (RR = 1.15, 95% CI 0.97-1.37; p = 0.11). There was a higher incidence of satisfactory separation from parents in the dexmedetomidine group (RR = 1.40; 95% CI 1.13-1.74; p = 0.002). Dexmedetomidine was also associated with a reduction in the incidence of emergence agitation (RR = 0.35; 95% CI 0.14-0.88; p = 0.02). Heart rate and mean arterial pressure were marginally lower in the dexmedetomidine group but without clinical repercussions. CONCLUSION: Compared with oral midazolam, intranasal dexmedetomidine demonstrated better separation from parents and lower incidence of emergence agitation in pediatric premedication, without a difference in satisfactory induction. Intranasal dexmedetomidine may be a safe and effective alternative to oral midazolam for premedication in pediatric patients.

[Translated article] Postsurgical analgesic efficacy by the intra-articular administration of ropivacaine with dexmedetomidine versus simple ropivacaine in patients undergoing knee arthroscopy.

The effective relief of postsurgical pain in patients undergoing knee arthroscopy is important to allow the initiation of activities of daily living. The objective of this study is to demonstrate the analgesic efficacy of dexmedetomidine as an adjuvant added to ropivacaine by the intra-articular route. METHOD: Seventy patients underwent knee arthroscopy which were randomly assigned into two groups (n=35). The RD group received ropivacaine 1.5mg/kg plus dexmedetomidine 1µg/kg intra-articularly. Group R received ropivacaine 1.5mg/kg intra-articularly. The analgesic effect was evaluated by measuring the intensity of pain (VAS score) and the duration of analgesia. RESULTS: A longer duration of the analgesic effect was observed in the RD group (655min) compared to the R group (318min) being statistically significant (p=0.03). CONCLUSION: Dexmedetomidine as an adjuvant to intra-articular ropivacaine improves the quality and duration of postoperative analgesia in patients undergoing knee arthroscopy.

Immunotherapeutic Properties of Dexmedetomidine on Pain Management and Cardiovascular Function in Videolaparoscopic Cholecystectomies: A Randomized, Two-Arm, Double-Blinded, Placebo-Controlled Trial.

BACKGROUND: Laparoscopy represented one of the most innovative surgical techniques approached in the surgery field. Dexmedetomidine association with general anesthesia promotes the response control to trauma by altering the neuroinflammatory reflex, provides better clinical outcomes in the postoperative period and reduces the excessive use of drugs with risk for addiction. This trial aims to evaluate the potential drug treatment of dexmedetomidine on organic function, with the targets in neuroinflammation, perioperative pain control and blood pressure measurements in a medium-sized surgical model. METHODS: Fifty-two patients were randomized in two groups: Sevoflurane and Dexmedetomidine - A (dexmedetomidine infusion [1 µg/kg loading, .2-.5 µg/kg/h thereafter]) vs Sevoflurane and Saline .9% - B. Three blood samples were collected at three times: before surgery, 4 to 6 hours after surgery and 24 hours postoperatively. The primary outcome was inflammatory and endocrine mediators dosage analisys. Finally, we evaluated pain and opioid use as secondary outcomes, also the hemodynamic values. RESULTS: In Dexmedetomidine group A, a reduction of Interleukin 6 was found during 4-6 hours after surgery. A reduction of IL-10 was noted in the measurement of its values 24 hours after the procedure, with statistical significance. Also, systolic and diastolic blood pressure, as well heart rate were attenuated, and there was a lower incidence of pain and opioid consumption in the first postoperative hour (P < .0001) in the anesthetic recovery room. CONCLUSIONS: Dexmedetomidine provided anti-inflammatory activity, sympatholytic effect and analgesia with cardiovascular safety. It reinforces the therapeutic nature of highly selective α2-adrenergic agonists when combined within anesthetic interventions.

Does dexmedetomidine reduce the risk of acute kidney injury after cardiac surgery? A meta-analysis of randomized controlled trials

Abstract Background: Acute Kidney Injury (AKI) is a common complication after cardiac surgery and has been associated with poor outcomes. Dexmedetomidine (DEX) has been shown to confer direct renoprotection based on some animal and clinical studies, but data from other trials came to the opposite conclusion following cardiac surgery. This meta-analysis was conducted to evaluate the effects of perioperative DEX administration on the occurrence of AKI and the outcomes after cardiac surgery. Methods: We searched databases including EMBASE, PubMed, and Cochrane CENTRAL for Randomized Controlled Trials (RCTs) focused on DEX for AKI in adult patients after cardiac surgery. The primary outcome was incidence of AKI. Secondary outcomes were Mechanical Ventilation (MV) duration, Intensive Care Unit (ICU) Length Of Stay (LOS), hospital LOS and mortality. Results: Fifteen trials enrolling 2907 study patients were collected in the meta-analyses. Compared with controls, DEX reduced the incidence of postoperative AKI (Odds Ratio [OR = 0.66]; 95% Confidence Interval [95% CI 0.48-0.91]; p = 0.01), and there was no significant difference between groups in postoperative mortality (OR = 0.63; 95% CI 0.32-1.26; p = 0.19), MV duration (Weighted Mean Difference [WMD = -0.44]; 95% CI -1.50-0.63; p = 0.42), ICU LOS (WMD = -1.19; 95% CI -2.89-0.51; p = 0.17), and hospital LOS (WMD = -0.31; 95% CI -0.76-0.15; p = 0.19). Conclusions: Perioperative DEX reduced the incidence of postoperative AKI in adult patients undergoing cardiac surgery. No significant decrease existed in mortality, MV duration, ICU LOS and hospital LOS owing to DEX administration.

Dexmedetomidine versus sufentanil as adjuvants to bupivacaine for brachial plexus block during upper extremity surgery: a randomized clinical trial

Abstract Background: Brachial plexus block (BPB) has been accepted as a reliable alternative for general anesthesia in upper limb surgeries. Adding adjuvant drugs like dexmedetomidine and sufentanil has been shown to have clinical and pharmacologic advantages. In this randomized parallel clinical trial, we aim to compare the effects of these two adjuvants for bupivacaine in BPB. Methods: In this double-blinded study, by using computer-assisted block randomization, 40 patients ranged from 20 to 65 years old and scheduled for elective upper limb surgeries were assigned to two equal study groups (n = 20), receiving 1 mL of 5 μg.mL-1 sufentanil (group S) or 1 mL of 100 μg.mL-1 dexmedetomidine (group D) in adjunction to 30 mL of 0.5% bupivacaine for supraclavicular BPB under the guidance of ultrasonography. Characteristics of local anesthesia and postoperative analgesia were evaluated (n = 40). Results: The duration of blocks significantly improved in group S (sensory: estimated median difference (EMD) [95%CI] = 100.0 [70.0~130.0], p < 0.001; motor: EMD [95%CI] = 120.0 [100.0~130.0], p < 0.001). Group S also had significantly longer postoperative analgesia and lower opioid consumption within 24 hours after the surgery (EMD [95%CI] = 4.0 [3.0~7.0], p < 0.001; EMD [95%CI] = -5.0 [-5.0~-5.0], p < 0.001; respectively). None of the patients showed adverse effects concerning vital signs, nausea, or vomiting. Conclusion: Our study showed that during ultrasound-guided supraclavicular BPB, sufentanil is a fairly better choice than dexmedetomidine as an adjuvant for bupivacaine and can provide preferable sensory and motor blocks. No significant side effects were seen in either of the study groups.

Foreign body ingestion due to detachment of pill dispenser tips in cats: a retrospective study of 13 cases.

OBJECTIVES: The aim of this study was to evaluate and describe 13 cases in which a pet piller broke during the administration of medication, and the tip was accidentally ingested by the cat. METHODS: A total of 15 presentations to the clinic were identified in a private practice database involving 13 cats in which the silicone tip broke. Two of these cats ingested foreign bodies on two separate occasions. Routine radiographic examination enabled the identification of silicone tips in all animals. On 2/15 occasions, the cats did not receive an emetic drug. Intramuscular xylazine (0.2 mg/kg) and dexmedetomidine (6 µg/kg) were administered to 12/15 and 1/15 cats, respectively. RESULTS: The cats were aged 3-17 years (mean age 11.00 ± 4.35 years). Vomiting occurred in 13 cats that received alpha-2 adrenoceptor agonists, although the silicone tip was recovered in only five occurrences. In 9/15 occurrences, endoscopy was performed under general inhalation anesthesia, and the silicone tip was successfully removed. Natural elimination occurred in only one case. CONCLUSIONS AND RELEVANCE: The use of pet pillers with detachable silicone tips increases the risk of accidental foreign body ingestion by animals. Therefore, guidelines regarding safety standards for manufacturing would be beneficial. No cat in this series developed clinical signs related to the ingestion of the piller tip, probably because of the quick presentation by the owners and early intervention, including endoscopic retrieval. Surgical intervention was not required in any case, including one in which the foreign body was lodged within the small intestine before being passed naturally by the cat.

Dexmedetomidine compared to low-dose ketamine better protected not only the brain but also the lungs in acute ischemic stroke.

BACKGROUND: Dexmedetomidine (DEX) and low-dose ketamine (KET) present neuroprotective effects in acute ischemic stroke (AIS); however, to date, no studies have evaluated which has better protective effects not only on the brain but also lungs in AIS. METHODS: AIS-induced Wistar rats (390 ± 30 g) were randomized after 24-h, receiving dexmedetomidine (STROKE-DEX, n = 10) or low-dose S(+)-ketamine (STROKE-KET, n = 10). After 1-h protective ventilation, perilesional brain tissue and lungs were removed for histologic and molecular biology analysis. STROKE animals (n = 5), receiving sodium thiopental but not ventilated, had brain and lungs removed for molecular biology analysis. Effects of DEX and KET mean plasma concentrations on alveolar macrophages, neutrophils, and lung endothelial cells, extracted primarily 24-h after AIS, were evaluated. RESULTS: In perilesional brain tissue, apoptosis did not differ between groups. In STROKE-DEX, compared to STROKE-KET, tumor necrosis factor (TNF)-α and vascular cell adhesion molecule-1 (VCAM-1) expressions were reduced, but no changes in nuclear factor erythroid 2-related factor-2 (Nrf2) and super oxide dismutase (SOD)-1 were observed. In lungs, TNF-α and VCAM-1 were reduced, whereas Nrf2 and SOD-1 were increased in STROKE-DEX. In alveolar macrophages, TNF-α and inducible nitric oxide synthase (M1 macrophage phenotype) were lower and arginase and transforming growth factor-ß (M2 macrophage phenotype) higher in STROKE-DEX. In lung neutrophils, CXC chemokine receptors (CXCR2 and CXCR4) were higher in STROKE-DEX. In lung endothelial cells, E-selectin and VCAM-1 were lower in STROKE-DEX. CONCLUSIONS: In the current AIS model, dexmedetomidine compared to low-dose ketamine reduced inflammation and endothelial cell damage in both brain and lung, suggesting greater protection.

Outcomes of dexmedetomidine as adjuvant drug in patients undergoing videolaparoscopic cholecystectomy: A randomized and prospective clinical trial.

OBJECTIVE: The repercussions of ischemia-reperfusion and inflammatory response to surgical injury may compromise the return of physiologic processes in video-laparoscopic surgeries. Dexmedetomidine, as an adjuvant drug in general anesthesia, alters the neuroinflammatory reaction, provides better clinical outcomes in the perioperative period, and may reduce the excessive use of chronic medication in patients with a history of addiction. This study evaluated the immunomodulatory potential of dexmedetomidine on perioperative organ function in video-laparoscopic cholecystectomy patients. METHODS: There were two groups: Sevoflurane and Dexmedetomidine A (26 patients) vs. Sevoflurane and Saline 0.9% B (26 patients). Three blood samples were collected three times: 1) before surgery, 2) 4-6h after surgery, and 3) 24h postoperatively. Inflammatory and endocrine mediators were protocolized for analysis. Finally, hemodynamic outcomes, quality upon awakening, pain, postoperative nausea and vomiting, and opioid use were compared between groups. RESULTS: We have demonstrated a reduction of Interleukin 6 six hours after surgery in group A: 34.10 (IQR 13.88-56.15) vs. 65.79 (IQR 23.13-104.97; p = 0.0425) in group B. Systolic blood pressure, diastolic blood pressure, and mean arterial pressure was attenuated in group A in their measurement intervals (p < 0.0001). There was a lower incidence of pain and opioid consumption in the first postoperative hour favoring this group (p < 0.0001). We noticed better quality upon awakening after the intervention when comparing the values of peripheral oxygen saturation and respiratory rate. CONCLUSIONS: Dexmedetomidine provided anti-inflammatory benefits and contributed to postoperative analgesia without the depressive side effects on the respiratory and cardiovascular systems commonly observed with opioids. TRIAL REGISTRATION: Immunomodulatory Effect of Dexmedetomidine as an Adjuvant Drug in Laparoscopic Cholecystectomies, NCT05489900, Registered 5 August 2022-Retrospectively registered, https://clinicaltrials.gov/ct2/show/NCT05489900?term=NCT05489900&draw=2&rank=1.

Does dexmedetomidine reduce the risk of acute kidney injury after cardiac surgery? A meta-analysis of randomized controlled trials.

BACKGROUND: Acute Kidney Injury (AKI) is a common complication after cardiac surgery and has been associated with poor outcomes. Dexmedetomidine (DEX) has been shown to confer direct renoprotection based on some animal and clinical studies, but data from other trials came to the opposite conclusion following cardiac surgery. This meta-analysis was conducted to evaluate the effects of perioperative DEX administration on the occurrence of AKI and the outcomes after cardiac surgery. METHODS: We searched databases including EMBASE, PubMed, and Cochrane CENTRAL for Randomized Controlled Trials (RCTs) focused on DEX for AKI in adult patients after cardiac surgery. The primary outcome was incidence of AKI. Secondary outcomes were Mechanical Ventilation (MV) duration, Intensive Care Unit (ICU) Length Of Stay (LOS), hospital LOS and mortality. RESULTS: Fifteen trials enrolling 2907 study patients were collected in the meta-analyses. Compared with controls, DEX reduced the incidence of postoperative AKI (Odds Ratio [OR = 0.66]; 95% Confidence Interval [95% CI 0.48-0.91]; p = 0.01), and there was no significant difference between groups in postoperative mortality (OR = 0.63; 95% CI 0.32-1.26; p = 0.19), MV duration (Weighted Mean Difference [WMD = -0.44]; 95% CI -1.50-0.63; p = 0.42), ICU LOS (WMD = -1.19; 95% CI -2.89-0.51; p = 0.17), and hospital LOS (WMD = -0.31; 95% CI -0.76-0.15; p = 0.19). CONCLUSIONS: Perioperative DEX reduced the incidence of postoperative AKI in adult patients undergoing cardiac surgery. No significant decrease existed in mortality, MV duration, ICU LOS and hospital LOS owing to DEX administration.

Comparison of two pharmacological semen collection times with α2-adrenergic agonist in domestic cats.

The use of α2-adrenergic agonists in association with urethral catheterization has been used as a technique for pharmacological semen collection in cats. The mechanism of action of this drug is the stimulation of adrenoreceptors in the vas deferens, which results in ejaculation. While medetomidine is the α2-agonist most commonly used in studies, ejaculation with the use of dexmedetomidine associated with ketamine has been effective, but with variable results. Therefore, further studies regarding the methodology of use are required to obtain better seminal quality. This study aimed to compare two pharmacological semen collection times after the association of dexmedetomidine (30 µg/kg, IM; Dormitor®, Zoetis), ketamine (5 mg/kg, IM; ketamine, Vetnil) and urethral catheterization using a tomcat probe (0.8 mm × 1.00 mm × 11 cm). The collections were divided into two experimental groups: G10 (N = 8; urethral catheterization after 10 min of anaesthesia) and G15 (N = 8; urethral catheterization after 15 min of anaesthesia). The ejaculates were evaluated for ejaculate volume, sperm concentration, morphology and kinetics using the CASA system. To compare the groups, the t-test and the Mann-Whitney U-test were used with a significance level of 5%. It was identified that ejaculate volume (G10: 22.62 ± 2.13 vs. G15: 26.81 ± 1.55; p < .001) and sperm concentration (G10: 48.10 × 106 ± 17.84 vs. G15: 90.18 × 106 ± 19.35; p < .001) was higher in G15 than in G10 and had a lower percentage of minor defects than G10 (G10: 3.12 ± 2.41 vs. G15: 1.00 ± 1.19; p = .043). Regarding the kinetic parameters, the results of G15 were better for total motility-TM (G10: 67.00 ± 10.33 vs. G15: 81.87 ± 7.99; p = .006) and faster cells-RAPID: (G10: 55.00 ± 16.63 vs. G15: 74.25 ± 11.94; p = .019); whereas a higher proportion of cells with slow speed-SLOW were seen in G10 (G10: 31.00 ± 12.07 vs. 17.12 ± 7.53; p = .015). Based on these findings, we suggest that collection via urethral catheterization should be performed 15 min after the application of ketamine-associated dexmedetomidine to obtain a better-quality ejaculate.

Repeated Administration of the Cannabinoid WIN Alters the Isoflurane-Sparing Effect of Morphine and Dexmedetomidine.

The impacts of morphine and dexmedetomidine on the MAC of isoflurane were studied in rats constantly medicated with the cannabinoid WIN 55,212-2. METHODS: Prior to the administration of morphine, the MAC was measured in both untreated rats (MAC (ISO)) and those treated with a cannabinoid (MAC (ISO + CANN)). The effects of morphine (MAC (ISO + MOR)) and dexmedetomidine (MAC (ISO + DEX)) on untreated rats and rats treated for 21 days with the cannabinoids (MAC (ISO + CANN + MOR)) and (MAC (ISO + CANN + DEX) were also studied. RESULTS: MAC (ISO) was 1.32 ± 0.06, and MAC (ISO + CANN) was 1.69 ± 0.09. MAC (ISO + MOR) was 0.97 ± 0.02 (26% less than MAC (ISO)). MAC (ISO + CANN + MOR) was 1.55 ± 0.08 (8% less than MAC (ISO + CANN)), MAC (ISO + DEX) was 0.68 ± 0.10 (48% less than MAC (ISO)), and MAC (ISO + CANN + DEX) was 0.67 ± 0.08 (60% less than MAC (ISO + CANN)). CONCLUSIONS: Medication with a cannabinoid for 21 days augmented the MAC of isoflurane. The sparing effect of morphine on isoflurane is lower in rats constantly medicated with a cannabinoid. The sparing effect of dexmedetomidine on the minimum alveolar concentration of isoflurane is greater in rats repeatedly medicated with a cannabinoid.

Effects of Dexmedetomidine on Immunomodulation and Pain Control in Videolaparoscopic Cholecystectomies: A Randomized, Two-Arm, Double-Blinded, Placebo-Controlled Trial.

AIM: Digital and robotic technology applications in laparoscopic surgery have revolutionized routine cholecystectomy. Insufflation of the peritoneal space is vital for its safety but comes at the cost of ischemia-reperfusion-induced intraabdominal organ compromise before the return of physiologic functions. Dexmedetomidine in general anesthesia promotes controlling the response to trauma by altering the neuroinflammatory reflex. This strategy may improve clinical outcomes in the postoperative period by reducing postoperative narcotic use and lowering the risk of subsequent addiction. In this study, the authors aimed to evaluate dexmedetomidine's therapeutic and immunomodulatory potential on perioperative organ function. METHODS: Fifty-two patients were randomized 1:1: group A-sevoflurane and dexmedetomidine (dexmedetomidine infusion [1 µg/kg loading, 0.2-0.5 µg/kg/h maintenance dose]), and group B-sevoflurane with saline 0.9% infusion as a placebo control. Three blood samples were collected: preoperatively (T0 h), 4-6 h after surgery (T4-6 h), and 24 h postoperatively (T24 h). The primary outcome was the level analysis of inflammatory and endocrine mediators. Secondary outcome measures were the time to return to normal preoperative hemodynamic parameters, spontaneous ventilation, and postoperative narcotic requirements to control surgical pain. RESULTS: A reduction of Interleukin 6 was found at 4-6 h after surgery in group A with a mean of 54.76 (27.15-82.37; CI 95%) vs. 97.43 (53.63-141.22); p = 0.0425) in group B patients. Systolic and diastolic blood pressure and heart rate were lower in group A patients, who also had a statistically significantly lower opioid consumption in the first postoperative hour when compared to group B patients (p < 0.0001). We noticed a similar return to spontaneous ventilation pattern in both groups. CONCLUSIONS: Dexmedetomidine decreased interleukin-6 4-6 h after surgery, likely by providing a sympatholytic effect. It provides good perioperative analgesia without respiratory depression. Implementing dexmedetomidine during laparoscopic cholecystectomy has a good safety profile and may lower healthcare expenditure due to faster postoperative recovery.

Appraisal of the Neuroprotective Effect of Dexmedetomidine: A Meta-Analysis.

Dexmedetomidine is an adrenergic receptor agonist that has been regarded as neuroprotective in several studies without an objective measure to it. Thus, the aim of this meta-analysis was to analyze and quantify the current evidence for the neuroprotective effects of dexmedetomidine in animals. The search was performed by querying the National Library of Medicine. Studies were included based on their language, significancy of their results, and complete availability of data on animal characteristics and interventions. Risk of bias was assessed using SYRCLE's risk of bias tool and certainty was assessed using the ARRIVE Guidelines 2.0. Synthesis was performed by calculating pooled standardized mean difference and presented in forest plots and tables. The number of eligible records included per outcome is the following: 22 for IL-1ß, 13 for IL-6, 19 for apoptosis, 7 for oxidative stress, 7 for Escape Latency, and 4 for Platform Crossings. At the cellular level, dexmedetomidine was found protective against production of IL-1ß (standardized mean difference (SMD) = - 4.3 [- 4.8; - 3.7]) and IL-6 (SMD = - 5.6 [- 6.7; - 4.6]), apoptosis (measured through TUNEL, SMD = - 6.0 [- 6.8; - 4.6]), and oxidative stress (measured as MDA production, SMD = - 2.0 [- 2.4; - 1.4]) exclusively in the central nervous system. At the organism level, dexmedetomidine improved behavioral outcomes measuring escape latency (SMD = - 2.4 [- 3.3; - 1.6]) and number of platform crossings (SMD = 9.1 [- 6.8; - 11.5]). No eligible study had high risk of bias and certainty was satisfactory for reproducibility in all cases. This meta-analysis highlights the complexity of adrenergic stimulation and sheds light into the mechanisms potentiated by dexmedetomidine, which could be exploited for improving current neuroprotective formulations.

The antioxidant effect of preischemic dexmedetomidine in a rat model: increased expression of Nrf2/HO-1 via the PKC pathway

Abstract Background The precise underlying mechanism of antioxidant effects of dexmedetomidine-induced neuroprotection against cerebral ischemia has not yet been fully elucidated. Activation of Nuclear factor erythroid 2-related factor (Nrf2) and Heme Oxygenase-1 (HO-1) represents a major antioxidant-defense mechanism. Therefore, we determined whether dexmedetomidine increases Nrf2/HO-1 expression after global transient cerebral ischemia and assessed the involvement of Protein Kinase C (PKC) in the dexmedetomidine-related antioxidant mechanism. Methods Thirty-eight rats were randomly assigned to five groups: sham (n = 6), ischemic (n = 8), chelerythrine (a PKC inhibitor; 5 mg.kg-1 IV administered 30 min before cerebral ischemia) (n = 8), dexmedetomidine (100 µg.kg-1 IP administered 30 min before cerebral ischemia (n = 8), and dexmedetomidine + chelerythrine (n = 8). Global transient cerebral ischemia (10 min) was applied in all groups, except the sham group; histopathologic changes and levels of nuclear Nrf2 and cytoplasmic HO-1 were examined 24 hours after ischemia insult. Results We found fewer necrotic and apoptotic cells in the dexmedetomidine group relative to the ischemic group (p< 0.01) and significantly higher Nrf2 and HO-1 levels in the dexmedetomidine group than in the ischemic group (p< 0.01). Additionally, chelerythrine co-administration with dexmedetomidine attenuated the dexmedetomidine-induced increases in Nrf2 and HO-1 levels (p< 0.05 and p< 0.01, respectively) and diminished its beneficial neuroprotective effects. Conclusion Preischemic dexmedetomidine administration elicited neuroprotection against global transient cerebral ischemia in rats by increasing Nrf2/HO-1 expression partly via PKC signaling, suggesting that this is the antioxidant mechanism underlying dexmedetomidine-mediated neuroprotection.

The impact of emergence delirium on hospital length of stay for children who underwent tonsillectomy/adenotonsillectomy: an observational retrospective study

Abstract Background Emergence Delirium (ED) is a combination of disturbance of perception and psychomotor agitation that is common in pediatric patients after general anesthesia, especially at preschool age. Since the effect of ED on the length of stay has been studied in adults but infrequently in children, the aim of this study was to investigate the relationship between ED and length of stay in this population. Methods A single center, retrospective, observational study was carried out in children who underwent tonsillectomy or adenotonsillectomy. The Pediatric Anesthesia Emergence Delirium (PAED) scale was used to assess ED. In addition to the time to hospital discharge (time frame 24 hours), drugs used, comorbidities, early postoperative complications, and pain were investigated if potentially associated with the complication. Results Four hundred sixteen children aged from 1.5 to 10 years (183 female, 233 male) were included. ED occurred in 25.5% of patients (n = 106). Patients were divided into the ED group and the No-ED group. The discharge time was similar in both groups. No significant differences were observed in the frequency of postoperative complications. The use of fentanyl or dexmedetomidine did not affect ED occurrence. The frequency of pain was greater in the ED group, both in the recovery room and in the ward (p= 0.01). Conclusions The occurrence of ED in children after tonsillectomy/adenotonsillectomy did not extend the length of stay.

Anesthetic effects of isoflurane and fentanyl infusion in capuchin monkeys (Sapajus sp) undergoing salpingectomy or deferentectomy, previously chemically restrained with ketamine-midazolam or ketamine-dexmedetomidine.

BACKGROUND: This study evaluated the anesthetic and cardiorespiratory effects of two anesthetic protocols for salpingectomy or deferentectomy in capuchin monkeys (Sapajus sp). MATERIALS AND METHODS: Five capuchin monkeys (5 per group) received ketamine (20 mg/kg) combined with midazolam (0.5 mg/kg; group KM) or dexmedetomidine (5 µg/kg; group KD) intramuscularly. Anesthesia is induced with propofol intravenously and maintained with isoflurane. Before the start of surgery, fentanyl 3 µg/kg was administered IV, and continuous infusion (10 µg/kg/min) IV was started. Times and quality of anesthetic recovery were evaluated postoperatively. RESULTS: KM and KD resulted in adequate chemical restraint. KD resulted in bradycardia. Intraoperative heart rate and systolic blood pressure were higher in KM than in KD. Both groups had smooth recovery. Time to standing was longer in KM than in KD. CONCLUSION: Both protocols allowed the performance of surgeries, with few cardiorespiratory effects. Anesthetic recovery was smooth and shorter in KD group.