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Oncoimmunology 2024Dexmedetomidine (DEX) is a highly selective α2-adrenoceptor agonist that is widely used in intensive and anesthetic care for its sedative and anxiolytic properties. DEX... (Review)
Review
Dexmedetomidine (DEX) is a highly selective α2-adrenoceptor agonist that is widely used in intensive and anesthetic care for its sedative and anxiolytic properties. DEX has the capacity to alleviate inflammatory pain while limiting immunosuppressive glucocorticoid stress during major surgery, thus harboring therapeutic benefits for oncological procedures. Recently, the molecular mechanisms of DEX-mediated anticancer effects have been partially deciphered. Together with additional preclinical data, these mechanistic insights support the hypothesis that DEX-induced therapeutic benefits are mediated the stimulation of adaptive anti-tumor immune responses. Similarly, published clinical trials including ancillary studies described an immunostimulatory role of DEX during the perioperative period of cancer surgery. The impact of DEX on long-term patient survival remains elusive. Nevertheless, DEX-mediated immunostimulation offers an interesting therapeutic option for onco-anesthesia. Our present review comprehensively summarizes data from preclinical and clinical studies as well as from ongoing trials with a distinct focus on the role of DEX in overcoming (tumor microenvironment (TME)-imposed) cancer therapy resistance. The objective of this update is to guide clinicians in their choice toward immunostimulatory onco-anesthetic agents that have the capacity to improve disease outcome.
Topics: Humans; Dexmedetomidine; Hypnotics and Sedatives; Neoplasms; Clinical Trials as Topic
PubMed: 38481729
DOI: 10.1080/2162402X.2024.2327143 -
JAMA Network Open Jan 2024Postpartum depression (PPD) is emerging as a major public health problem worldwide. Although the particular period and context in which PPD occurs provides an... (Randomized Controlled Trial)
Randomized Controlled Trial
IMPORTANCE
Postpartum depression (PPD) is emerging as a major public health problem worldwide. Although the particular period and context in which PPD occurs provides an opportunity for preventive interventions, there is still a lack of pharmacologic prevention strategies for PPD.
OBJECTIVE
To assess the efficacy and safety of dexmedetomidine for prevention of PPD among women with prenatal depression undergoing cesarean delivery.
DESIGN, SETTING, AND PARTICIPANTS
This randomized clinical trial enrolled 338 women who screened positive for prenatal depression at 2 hospitals in Hunan, China from March 28, 2022, to April 16, 2023. Women with an Edinburgh Postnatal Depression Scale score of more than 9 who were 18 years of age or older and were scheduled for elective cesarean delivery were eligible.
INTERVENTIONS
Eligible participants were randomly assigned in a 1:1 ratio to either the dexmedetomidine group or the control group via centrally computer-generated group randomization. Dexmedetomidine, 0.5 μg/kg and 0.9% saline were intravenously infused for 10 minutes after delivery in the dexmedetomidine and control groups, respectively. After infusion, sufentanil or dexmedetomidine plus sufentanil was administered via patient-controlled intravenous analgesia for 48 hours in the control group and dexmedetomidine group, respectively.
MAIN OUTCOMES AND MEASURES
The primary outcome was positive PPD screening results at 7 and 42 days post partum, defined as a postpartum Edinburgh Postnatal Depression Scale score of more than 9. Analysis was on an intention-to-treat basis.
RESULTS
All 338 participants were female, with a mean (SD) age of 31.5 (4.1) years. Positive PPD screening incidence at 7 and 42 days post partum in the dexmedetomidine group vs the control group was significantly decreased (day 7, 21 of 167 [12.6%] vs 53 of 165 [32.1%]; risk ratio, 0.39 [95% CI, 0.25-0.62]; P < .001; day 42, 19 of 167 [11.4%] vs 50 of 165 [30.3%]; risk ratio, 0.38 [95% CI, 0.23-0.61]; P < .001). The dexmedetomidine group showed no significant difference in adverse events vs the control group (46 of 169 [27.2%] vs 33 of 169 [19.5%]; P = .10), but the incidence of hypotension increased (31 of 169 [18.3%] vs 16 of 169 [9.5%]; risk ratio, 2.15 [95% CI, 1.13-4.10]; P = .02).
CONCLUSIONS AND RELEVANCE
Dexmedetomidine administration in the early postpartum period significantly reduced the incidence of a positive PPD screening and maintained a favorable safety profile.
TRIAL REGISTRATION
Chinese Clinical Trial Registry Identifier: ChiCTR2200057213.
Topics: Adult; Female; Humans; Pregnancy; Administration, Intravenous; Depression, Postpartum; Dexmedetomidine; Sufentanil
PubMed: 38270949
DOI: 10.1001/jamanetworkopen.2023.53252 -
Drug Design, Development and Therapy 2023Postoperative delirium (POD) is of great concern as a complication of surgery in older adult patients. Sedation strategies influence the development of POD. This study... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Postoperative delirium (POD) is of great concern as a complication of surgery in older adult patients. Sedation strategies influence the development of POD. This study compared how sedation strategies administered during spinal anesthesia influenced POD in patients aged ≥65 years undergoing elective surgery for hip fracture repair.
PATIENTS AND METHODS
A randomized clinical trial was conducted from 1 August 2021 to 30 June 2022 at a single academic medical center. Two hundred and twenty-six patients were randomly divided into four groups: lighter sedation with propofol (LP), heavier sedation with propofol (HP), lighter sedation with dexmedetomidine (LD), and heavier sedation with dexmedetomidine (HD). The incidence of delirium was the primary outcome and was assessed daily by the blinded Confusion Assessment Method.
RESULTS
There was a significant association between dexmedetomidine (LD+HD group) and a lower incidence of delirium (11.9% [13/109] vs the propofol group (23.6% [26/110]; Risk ratio, 0.51; 95% CI, 0.274 to 0.929; p=0.024). In the propofol group, heavier sedation had a higher rate of POD (32.7% [18/55] vs the lighter sedation group (14.5% [8/55]; Risk ratio, 2.25; 95% CI, 1.069 to 4.736; p=0.025).
CONCLUSION
Dexmedetomidine was associated with a lower incidence of delirium than that with propofol among older patients with hip fractures. In patients that received propofol, heavier sedation was associated with high incidence of POD.
Topics: Humans; Aged; Propofol; Emergence Delirium; Hypnotics and Sedatives; Dexmedetomidine; Anesthesia, Spinal; Delirium; Postoperative Complications
PubMed: 38169975
DOI: 10.2147/DDDT.S439543 -
Frontiers in Pediatrics 2023To compare the effects of intranasal dexmedetomidine (Dex) and oral midazolam in the preoperative medication of children by using a method of meta-analysis. (Review)
Review
OBJECTIVE
To compare the effects of intranasal dexmedetomidine (Dex) and oral midazolam in the preoperative medication of children by using a method of meta-analysis.
METHODS
Cochrane Library, Pubmed, Embase, and Web of Science were searched from inception to July 2023. Randomized controlled trials (RCTs) of intranasal Dex vs. oral midazolam in pediatric premedication were collected. Stata 15.0 statistical software was used to analyze the collected data. Relative risk (RR) and 95% confidence interval (CI) were used as effect sizes.
RESULTS
A total of 11 studies with 824 children were included, containing 415 patients in the Dex group and 409 patients in the midazolam group. Compared with the oral midazolam group, the intranasal Dex group had a better preoperative sedation effect at parent-child separation (RR = 1.37, 95% CI: 1.14-1.64) and anesthesia induction (RR = 2.08, 95% CI: 1.03-4.22). In addition, there was no significant difference in the incidence of analgesia remedy (RR = 0.60, 95% CI: 0.36-1.00) the acceptance of anesthesia masks (RR = 0.97, 95% CI: 0.83-1.12), and incidence of adverse events between (RR = 0.25, 95% CI: 0.06-1.13, = 0.072) between the intranasal Dex and oral midazolam groups.
CONCLUSION
Compared with oral midazolam, intranasal Dex has better sedative effects of parent-child separation and anesthesia induction in pediatric premedication, but there was no difference in the incidence of anesthesia remedy, anesthesia mask acceptance, and incidence of adverse events. Therefore, compared with oral midazolam, intranasal Dex is a better choice for premedication in children.
PubMed: 38027288
DOI: 10.3389/fped.2023.1264081 -
Journal of Pain Research 2023Cancer-related pain is one of the most common and incapacitating symptoms for cancer patients. Cancer pain can be caused by diagnostic or therapeutic procedures, side... (Review)
Review
Cancer-related pain is one of the most common and incapacitating symptoms for cancer patients. Cancer pain can be caused by diagnostic or therapeutic procedures, side effects and toxicity from therapy, or the cancer itself. Uncontrolled cancer-related pain is associated with inadequate quality of life and reduced functional status. Optimal pain management during the perioperative period requires a tailored approach. Interventions that are recommended for the management of acute surgical pain include regional anesthesia, local anesthetic infusions, non-opioid analgesics (ketamine, dexmedetomidine, lidocaine, and non-steroidal anti-inflammatory drugs), and opioids. Despite continued research efforts and advances in cancer treatment, opioids remain the most effective medication to treat moderate to severe cancer-related pain; however, their role has been changing significantly due to the opioid epidemic and opioid misuse. While pre-clinical and retrospective studies have shown a negative association between opioid use and cancer outcomes, randomized control trials have failed to confirm this association. The purpose of this review is to summarize the pharmacological management of acute cancer-related pain during the perioperative period with an emphasis on cancer recurrence.
PubMed: 38078017
DOI: 10.2147/JPR.S432444 -
Anesthesia and Analgesia Aug 2023Myocardial infarction is a common perioperative complication, and blood flow restoration causes ischemia/reperfusion injury (IRI). Dexmedetomidine (DEX) pretreatment can...
BACKGROUND
Myocardial infarction is a common perioperative complication, and blood flow restoration causes ischemia/reperfusion injury (IRI). Dexmedetomidine (DEX) pretreatment can protect against cardiac IRI, but the mechanism is still insufficiently understood.
METHODS
In vivo, myocardial ischemia/reperfusion (30 minutes/120 minutes) was induced via ligation and then reperfusion of the left anterior descending coronary artery (LAD) in mice. Intravenous infusion of 10 μg/kg DEX was performed 20 minutes before ligation. Moreover, the α2-adrenoreceptor antagonist Yohimbine and STAT3 inhibitor Stattic were applied 30 minutes ahead of DEX infusion. In vitro, hypoxia/reoxygenation (H/R) with DEX pretreatment for 1 hour was performed in isolated neonatal rat cardiomyocytes. In addition, Stattic was applied before DEX pretreatment.
RESULTS
In the mouse cardiac ischemia/reperfusion model, DEX pretreatment lowered the serum creatine kinase-MB isoenzyme (CK-MB) levels (2.47 ± 0.165 vs 1.55 ± 0.183; P < .0001), downregulated the inflammatory response ( P ≤ .0303), decreased 4-hydroxynonenal (4-HNE) production and cell apoptosis ( P = .0074), and promoted the phosphorylation of STAT3 (4.94 ± 0.690 vs 6.68 ± 0.710, P = .0001), which could be blunted by Yohimbine and Stattic. The bioinformatic analysis of differentially expressed mRNAs further confirmed that STAT3 signaling might be involved in the cardioprotection of DEX. Upon H/R treatment in isolated neonatal rat cardiomyocytes, 5 μM DEX pretreatment improved cell viability ( P = .0005), inhibited reactive oxygen species (ROS) production and calcium overload (both P ≤ .0040), decreased cell apoptosis ( P = .0470), and promoted STAT3 phosphorylation at Tyr705 (0.102 ± 0.0224 vs 0.297 ± 0.0937; P < .0001) and Ser727 (0.586 ± 0.177 vs 0.886 ± 0.0546; P = .0157), which could be abolished by Stattic.
CONCLUSIONS
DEX pretreatment protects against myocardial IRI, presumably by promoting STAT3 phosphorylation via the α2-adrenoreceptor in vivo and in vitro.
Topics: Animals; Mice; Rats; Apoptosis; Creatine Kinase, MB Form; Dexmedetomidine; Disease Models, Animal; Hypoxia; Myocardial Ischemia; Myocardial Reperfusion Injury; Myocardium; Reperfusion Injury; Signal Transduction; Receptors, Adrenergic, alpha
PubMed: 37145970
DOI: 10.1213/ANE.0000000000006487 -
Journal of Clinical Medicine Research Sep 2023The aim of the study was to evaluate the feasibility of the opioid-free anesthesia (OFA) technique with dexmedetomidine, esketamine, and lidocaine among patients...
BACKGROUND
The aim of the study was to evaluate the feasibility of the opioid-free anesthesia (OFA) technique with dexmedetomidine, esketamine, and lidocaine among patients diagnosed with benign breast mass and scheduled for lumpectomy.
METHODS
We enrolled 80 female patients who were aged from 18 to 60 years, graded with American Society of Anesthesiologists physical status I or II, diagnosed with benign breast mass, and scheduled for lumpectomy. These patients were randomly treated with OFA or opioid-based anesthesia (OBA). Dexmedetomidine-esketamine-lidocaine and sufentanil-remifentanil were administered in OFA and OBA group, respectively. We mainly compared the analgesic efficacy of OFA and OBA technique, as well as intraoperative hemodynamics, the quality of recovery, and satisfaction score of patients.
RESULTS
There was no significant difference between the two groups with regard to visual analogue scale (VAS) score at 2, 12, and 24 h after extubation. However, the time to first rescue analgesic was prolonged in OFA group than that in OFB group (6.18 ± 1.00 min vs. 7.40 ± 0.92 min, P = 0.000). Further, mean arterial pressure and heart rate at T0 (entering operating room), T1 (before anesthesia induction), T2 (immediately after intubation), T3, T4, and T5 (1, 5, and 10 min after surgical incision, respectively) were significantly higher in OFA group than that in OBA group. Incidence of hypotension and bradycardia was lower in OFA group. Consistently, fewer patients in OFA group consumed atropine (8% vs. 32%, P = 0.019) and ephedrine (5% vs. 38%, P = 0.001) compared to OBA group. Furthermore, patients in OFA group had a longer awakening time (7.14 ± 2.63 min vs. 4.54 ± 1.14 min, P = 0.000) and recovery time of orientation (11.76 ± 3.15 min vs. 6.92 ± 1.19 min, P = 0.000). Fewer patients in the OFA group experienced postoperative nausea and vomiting (PONV) (11% vs. 51%, P = 0.000) and consumed ondansetron (5% vs. 35%, P = 0.003) compared to OBA group. And patients in OFA group had a higher satisfaction score than those in OBA group (9 (8 - 9) vs. 7 (7 - 8), P = 0.000).
CONCLUSION
For patients undergoing lumpectomy, OFA technique with dexmedetomidine-esketamine-lidocaine showed a better postoperative analgesic efficacy, a more stable hemodynamics, and a lower incidence of PONV. However, such advantage of OFA technique should be weighed against a longer awakening time and recovery time of orientation in clinical practice.
PubMed: 37822850
DOI: 10.14740/jocmr5000 -
Medical Gas Research 2024Postoperative sore throat is one well-recognized complication, occurring most frequently following tracheal intubation. Effective prevention of postoperative sore throat... (Randomized Controlled Trial)
Randomized Controlled Trial
Comparison of adding magnesium sulfate, dexmedetomidine and ondansetron to lidocaine for gargling before laryngoscopy and endotracheal intubation to prevent sore throat: a randomized clinical trial.
Postoperative sore throat is one well-recognized complication, occurring most frequently following tracheal intubation. Effective prevention of postoperative sore throat has been recognized as a top priority, bringing pleasant feelings and satisfaction to patients. This study aimed to assess the efficacy of magnesium sulfate, dexmedetomidine and ondansetron gargle with lidocaine administrated prior to laryngoscopy and tracheal intubation for postoperative sore throat prevention alongside hemodynamic management. This double-blind randomized clinical trial enrolled 105 general anesthesia-administered patients who had undergone laryngoscopy and endotracheal intubation, and they were equally randomized into three groups: magnesium sulfate, dexmedetomidine, and ondansetron groups. No significant intergroup difference was seen in oxygen saturation, non-invasive blood pressure, heart rate, duration of surgery, postoperative complications, analgesic consumption, and incidence of cough and hoarseness. The results showed statistically significant intergroup differences in pain scores and average pain intensity in the dexmedetomidine group was significantly lower than the other groups. Results suggest that dexmedetomidine gargle with lidocaine before general anesthesia induction could be recommended as an option depending on the patient's general condition and the anesthesiologist's discretion.
Topics: Humans; Lidocaine; Magnesium Sulfate; Dexmedetomidine; Ondansetron; Laryngoscopy; Pain; Pharyngitis; Intubation, Intratracheal
PubMed: 37929508
DOI: 10.4103/2045-9912.372664 -
Ageing Research Reviews Jun 2024Delirium is a common condition across different settings and populations. The interventions for preventing and managing this condition are still poorly known. The aim of... (Review)
Review
Delirium is a common condition across different settings and populations. The interventions for preventing and managing this condition are still poorly known. The aim of this umbrella review is to synthesize and grade all preventative and therapeutic interventions for delirium. We searched five databases from database inception up to March 15th, 2023 and we included meta-analyses of randomized controlled trials (RCTs) to decrease the risk of/the severity of delirium. From 1959 records after deduplication, we included 59 systematic reviews with meta-analyses, providing 110 meta-analytic estimates across populations, interventions, outcomes, settings, and age groups (485 unique RCTs, 172,045 participants). In surgery setting, for preventing delirium, high GRADE evidence supported dexmedetomidine (RR=0.53; 95%CI: 0.46-0.67, k=13, N=3988) and comprehensive geriatric assessment (OR=0.46; 95%CI=0.32-0.67, k=3, N=496) in older adults, dexmedetomidine in adults (RR=0.33, 95%CI=0.24-0.45, k=7, N=1974), A2-adrenergic agonists after induction of anesthesia (OR= 0.28, 95%CI= 0.19-0.40, k=10, N=669) in children. High certainty evidence did not support melatonergic agents in older adults for delirium prevention. Moderate certainty supported the effect of dexmedetomidine in adults and children (k=4), various non-pharmacological interventions in adults and older people (k=4), second-generation antipsychotics in adults and mixed age groups (k=3), EEG-guided anesthesia in adults (k=2), mixed pharmacological interventions (k=1), five other specific pharmacological interventions in children (k=1 each). In conclusion, our work indicates that effective treatments to prevent delirium differ across populations, settings, and age groups. Results inform future guidelines to prevent or treat delirium, accounting for safety and costs of interventions. More research is needed in non-surgical settings.
Topics: Humans; Delirium; Dexmedetomidine; Randomized Controlled Trials as Topic
PubMed: 38677599
DOI: 10.1016/j.arr.2024.102313 -
Anesthesiology Jun 2024Both dexamethasone and dexmedetomidine increase the duration of analgesia of peripheral nerve blocks. The authors hypothesized that combined intravenous dexamethasone... (Randomized Controlled Trial)
Randomized Controlled Trial
Combined Dexamethasone and Dexmedetomidine as Adjuncts to Popliteal and Saphenous Nerve Blocks in Patients Undergoing Surgery of the Foot or Ankle: A Randomized, Blinded, Placebo-controlled Clinical Trial.
BACKGROUND
Both dexamethasone and dexmedetomidine increase the duration of analgesia of peripheral nerve blocks. The authors hypothesized that combined intravenous dexamethasone and intravenous dexmedetomidine would result in a greater duration of analgesia when compared with intravenous dexamethasone alone and placebo.
METHODS
The authors randomly allocated participants undergoing surgery of the foot or ankle under general anesthesia and with a combined popliteal (sciatic) and saphenous nerve block to a combination of 12 mg dexamethasone and 1 µg/kg dexmedetomidine, 12 mg dexamethasone, or placebo (saline). The primary outcome was the duration of analgesia measured as the time from block performance until the first sensation of pain in the surgical area as reported by the participant. The authors predefined a 33% difference in the duration of analgesia as clinically relevant.
RESULTS
A total of 120 participants from two centers were randomized and 119 analyzed for the primary outcome. The median [interquartile range] duration of analgesia was 1,572 min [1,259 to 1,715] with combined dexamethasone and dexmedetomidine, 1,400 min [1,133 to 1,750] with dexamethasone alone, and 870 min [748 to 1,138] with placebo. Compared with placebo, the duration was greater with combined dexamethasone and dexmedetomidine (difference, 564 min; 98.33% CI, 301 to 794; P < 0.001) and with dexamethasone (difference, 489 min; 98.33% CI, 265 to 706; P < 0.001). The prolongations exceeded the authors' predefined clinically relevant difference. The duration was similar when combined dexamethasone and dexmedetomidine was compared with dexamethasone alone (difference, 61 min; 98.33% CI, -222 to 331; P = 0.614).
CONCLUSIONS
Dexamethasone with or without dexmedetomidine increased the duration of analgesia in patients undergoing surgery of the foot or ankle with a popliteal (sciatic) and saphenous nerve block. Combined dexamethasone and dexmedetomidine did not increase the duration of analgesia when compared with dexamethasone.
Topics: Humans; Dexmedetomidine; Dexamethasone; Nerve Block; Male; Female; Foot; Middle Aged; Ankle; Double-Blind Method; Drug Therapy, Combination; Aged; Pain, Postoperative; Adult; Sciatic Nerve
PubMed: 38489226
DOI: 10.1097/ALN.0000000000004977