Analgesic Mechanism of Dexmedetomidine and Esketamine in Rats with Spinal Cord Injury.

BACKGROUND: Spinal cord injury (SCI) is usually caused by external direct or indirect factors, and with a high morbidity and mortality rate. The aim of this study was to observe the effects of Dexmedetomidine (DEX) combined with Esketamine (ESK) on pain behavior and potential analgesic mechanisms in rats with SCI. The goal was to provide a reliable multimodal analgesic medication regimen for SCI. METHODS: Thirty rats were divided into five groups with six rats in each group: Sham group, SCI group, DEX group, ESK group, and DEX+ESK group. The SCI model in rats was constructed, and the motor function of hind limbs of rats was measured using Basso Beattie Bresnahan (BBB) locomotor rating scale and inclined plate test. The levels of interleukin 18 (IL-18), interleukin 1ß (IL-1ß), and tumor necrosis factor-α (TNF-α) in the spinal cord were determined by enzyme-linked immunosorbent assay (ELISA). The expressions of substance P (SP), neurokinin-1 receptor (NK-1R), B cell lymphoma-2 (Bcl-2), and Bcl2-associated X protein (Bax) in the rats' spinal cord were measured by Western blot assay. The viability of spinal astrocytes was evaluated by 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. RESULTS: After 7 days, the BBB scores were significantly higher in the DEX, ESK, and DEX+ESK groups compared to the SCI group (p < 0.01). Additionally, the DEX+ESK group had significantly higher scores than both the DEX and ESK groups (p < 0.01). The maximum angle of the DEX (p < 0.05), ESK (p < 0.05), and DEX+ESK groups (p < 0.01) were higher than the SCI group, and the maximum angle of DEX+ESK group was higher than DEX and ESK groups (p < 0.05). The levels of IL-18, IL-1ß, and TNF-α in the DEX, ESK, and DEX+ESK groups were lower than the SCI group (p < 0.01), while the DEX+ESK group had significantly lower IL-18, IL-1ß, and TNF-α levels than the DEX and ESK groups (p < 0.01). The levels of SP (p < 0.01) and NK-1R (p < 0.05) were lower in the DEX, ESK, and DEX+ESK groups compared to the SCI group, and the levels of SP and NK-1R were lower in the DEX+ESK group compared to the DEX and ESK groups (p < 0.01). The DEX and ESK groups suppressed the activity of spinal astrocytes (p < 0.01), however, the DEX+ESK group had larger effects on spinal astrocytes than the ESK group (p < 0.05). CONCLUSIONS: Treatment using DEX combined with ESK improves the motor function, inhibits inflammation and astrocyte activity, and exerts analgesic effects on rats with SCI. These findings can serve as a reference for the selection of multi-modal analgesics.

Thoracic spinal anesthesia with intrathecal sedation for lower back surgery: a retrospective cohort study.

Background: Spinal anesthesia (SA) is a good alternative to general anesthesia (GA) for spine surgery. Despite that, a few case series concern the use of thoracic spinal anesthesia for short-duration surgical interventions. In search of an alternative approach to GA and a better opioid-free modality, we aimed to investigate the safety, feasibility, and patient satisfaction of thoracic SA for spine surgery. Materials and methods: We analyzed retrospectively a cohort of 24 patients operated on for a degenerative and osteoporotic pathology of the lower thoracic and lumbar spine. Data was collected from medical records, including clinical notes, operative and anesthesia records, and patient questionnaires. Results: Twenty-one surgeries for herniated discs, two for degenerative spinal stenosis, and one for multi-level osteoporotic vertebral body fractures were performed under spinal anesthesia with intrathecal sedation. In all cases, we applied 0.5% isobaric bupivacaine and the following adjuvants: midazolam, clonidine or dexmedetomidine, and dexamethasone. We boosted the anesthesia with local ropivacaine due to inefficient sensory block in two patients. Nobody in the cohort received intravenous opioids, non-steroidal anti-inflammatory drugs, or additional sedation intraoperatively. Postoperative painkillers were upon the patient's request. No significant complications were detected. Conclusion: Thoracic spinal anesthesia incorporating adjuvants such as midazolam, clonidine or dexmedetomidine, and dexamethasone demonstrates not only efficient conditions for spine surgery, a favorable safety profile, high patient satisfaction, and intrathecal sedation but also effective opioid-free pain management.

Intravenous infusion of dexmedetomidine during the surgery to prevent postoperative delirium and postoperative cognitive dysfunction undergoing non-cardiac surgery: a meta-analysis of randomized controlled trials.

BACKGROUND: Dexmedetomidine plays a pivotal role in mitigating postoperative delirium and cognitive dysfunction while enhancing the overall quality of life among surgical patients. Nevertheless, the influence of dexmedetomidine on such complications in various anaesthesia techniques remains inadequately explored. As such, in the present study, a meta-analysis was conducted to comprehensively evaluate its effects on postoperative delirium and cognitive dysfunction. METHODS: A number of databases were searched for randomised controlled trials comparing intravenous dexmedetomidine to other interventions in preventing postoperative delirium and cognitive dysfunction in non-cardiac and non-neurosurgical patients. These databases included PubMed, Embase, and Cochrane Library. Statistical analysis and graphing were performed using Review Manager, STATA, the second version of the Cochrane risk-of-bias tool for randomised controlled trials, and GRADE profiler. MAIN RESULTS: This meta-analysis comprised a total of 24 randomised controlled trials, including 20 trials assessing postoperative delirium and 6 trials assessing postoperative cognitive dysfunction. Across these 24 studies, a statistically significant positive association was observed between intravenous administration of dexmedetomidine and a reduced incidence of postoperative delirium (RR: 0.55; 95% CI 0.47 to 0.64, p < 0.00001, I2 = 2%) and postoperative cognitive dysfunction (RR: 0.60; 95% CI 0.38 to 0.96, p = 0.03, I2 = 60%). Subgroup analysis did not reveal a significant difference in the incidence of postoperative delirium between the general anaesthesia and non-general anaesthesia groups, but a significant difference was observed in the incidence of postoperative cognitive dysfunction. Nonetheless, when the data were pooled, it was evident that the utilisation of dexmedetomidine was associated with an increased incidence of hypotension (RR: 1.42; 95% CI 1.08 to 1.86, p = 0.01, I2 = 0%) and bradycardia (RR: 1.66; 95% CI 1.23 to 2.26, p = 0.001, I2 = 0%) compared with other interventions. However, there was no significantly higher occurrence of hypertension in the DEX groups (RR = 1.35, 95% CI 0.81-2.24, p = 0.25, I2 = 0%). CONCLUSION: Compared with other interventions, intravenous dexmedetomidine infusion during non-cardiac and non-neurosurgical procedures may significantly reduce the risk of postoperative delirium and cognitive dysfunction. The results of subgroup analysis reveal a consistent preventive effect on postoperative delirium in both general and non-general anaesthesia groups. Meanwhile, continuous infusion during general anaesthesia was more effective in reducing the risk of cognitive dysfunction. Despite such findings, hypotension and bradycardia were more frequent in patients who received dexmedetomidine during surgery.

NIR-II nanoprobes for investigating the glymphatic system function under anesthesia and stroke injury.

The glymphatic system plays an important role in the transportation of cerebrospinal fluid (CSF) and the clearance of metabolite waste in brain. However, current imaging modalities for studying the glymphatic system are limited. Herein, we apply NIR-II nanoprobes with non-invasive and high-contrast advantages to comprehensively explore the function of glymphatic system in mice under anesthesia and cerebral ischemia-reperfusion injury conditions. Our results show that the supplement drug dexmedetomidine (Dex) enhances CSF influx in the brain, decreases its outflow to mandibular lymph nodes, and leads to significant differences in CSF accumulation pattern in the spine compared to isoflurane (ISO) alone, while both ISO and Dex do not affect the clearance of tracer-filled CSF into blood circulation. Notably, we confirm the compromised glymphatic function after cerebral ischemia-reperfusion injury, leading to impaired glymphatic influx and reduced glymphatic efflux. This technique has great potential to elucidate the underlying mechanisms between the glymphatic system and central nervous system diseases.

Real-time ultrasound-guided sacral plexus block combined with mild sedation for hemorrhoidectomy and hemorrhoidal artery ligation in a patient with amyotrophic lateral sclerosis: a case report.

BACKGROUND: Patients with amyotrophic lateral sclerosis present perioperative challenges for clinical anesthesiologists for anesthesia-associated complications. CASE PRESENTATION: A 54-year-old Han woman with a 2-year history of amyotrophic lateral sclerosis was scheduled for hemorrhoidectomy and hemorrhoidal artery ligation. We performed real-time ultrasound-guided sacral plexus block with dexmedetomidine under standard monitoring. The anesthesia method met the surgical demands and avoided respiratory complications during the procedures. There was no neurological deterioration after the surgery and 3 months after, the patient was discharged. CONCLUSIONS: Real-time ultrasound-guided sacral plexus block combined with mild sedation may be an effective and safe technique in patients with amyotrophic lateral sclerosis undergoing hemorrhoidectomy and hemorrhoidal artery ligation.

Evaluation of the efficacy of silymarin and dexmedetomidine on kidney and lung tissue in the treatment of sepsis in rats with cecal perforation.

Sepsis is a systemic inflammatory response syndrome that develops in the host against microorganisms. This response develops away from the primary infection site and results in end-organ damage. The present study aimed to investigate the protective and therapeutic effects on lung and kidney tissue of silymarin (S) and dexmedetomidine (DEX) applied 1 h before and after sepsis induced by the cecal ligation and puncture (CLP) method in rats. A total of 62 rats was randomly divided into eight groups: i) Control (n=6); ii) cecal perforation (CLP; n=8); iii) S + CLP (n=8; S + CLP; S administered 1 h before CPL); iv) CLP + S (n=8; S administered 1 h after CLP); v) DEX + CLP (n=8; D + CLP; DEX administered 1 h before CLP); vi) CLP + D (n=8; DEX administered 1 h after CLP); vii) SD + CLP (n=8; S and DEX administered 1 h before CLP) and viii) CLP + SD (n=8; S and DEX administered 1 h after CLP). After the cecum filled with stool, it was tied with 3/0 silk under the ileocecal valve and the anterior surface of the cecum was punctured twice with an 18-gauge needle. A total of 100 mg/kg silymarin and 100 µg/kg DEX were administered intraperitoneally to the treatment groups. Lung and kidney tissue samples were collected to evaluate biochemical and histopathological parameters. In the histopathological examination, all parameters indicating kidney injury; interstitial edema, peritubular capillary dilatation, vacuolization, ablation of tubular epithelium from the basement membrane, loss of brush border in the proximal tubule epithelium, cell swelling and nuclear defragmentation; were increased in the CLP compared with the control group. Silymarin administration increased kidney damage, including ablation of tubular epithelium from the basement membrane, compared with that in the CLP group. DEX significantly reduced kidney damage compared with the CLP and silymarin groups. The co-administration of DEX + silymarin decreased kidney damage, although it was not as effective as DEX-alone. To conclude, intraperitoneal DEX ameliorated injury in CLP rats. DEX + silymarin partially ameliorated injury but silymarin administration increased damage. As a result, silymarin has a negative effects with this dosage and DEX has a protective effect. In the present study, it was determined that using the two drugs together had a greater therapeutic effect than silymarin and no differences in the effects were not observed any when the application times of the agents were changed.

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.

Dexamethasone versus Dexmedetomidine as Adjuvants in Ultrasound Popliteal Sciatic Nerve Block for Hallux Valgus Surgery: A Mono-Centric Retrospective Comparative Study.

Background and Aim: Ultrasound popliteal sciatic nerve block (UPSNB) is commonly performed in foot and ankle surgery. This study aims to assess the use of dexmedetomidine and dexamethasone as adjuvants in UPSNB for hallux valgus (HV) surgery, comparing their efficacy in producing motor and sensory block and controlling postoperative pain. The adverse event rate was also evaluated. Methods: This mono-centric retrospective study included 62 adult patients undergoing HV surgery: 30 patients received lidocaine 2% 200 mg, ropivacaine 0.5% 50 mg and dexamethasone 4 mg (Group 1), whereas 32 patients received lidocaine 2% 200 mg, ropivacaine 0.5% 50 mg, and dexmedetomidine 1 mcg/Kg (Group 2). At first, the visual analogue scale (VAS) was evaluated after 48 hours. The other outcomes were time to motor block regression, evaluation of the first analgesic drug intake, analgesic effect, adverse effects (hemodynamic disorders, postoperative nausea and vomiting (PONV)) and patient satisfaction. The continuous data were analyzed with student's t-test and the continuous one with χ2. Statistical significance was set at a p-value lower than 0.05. Results: No significant difference was found in VAS after 48 hours (4.5 ± 1.6 vs 4.7 ± 1.7, p = 0.621) to motor block regression (18.9 ± 6.0 vs 18.7 ± 6, p = 0.922). The number of patients that took their first analgesic drug in the first 48 h (p = 0.947 at 6 hours; p = 0.421 at 12 hours; p = 0.122 at 24 hours and p = 0.333 at 48 hours) were not significant. A low and similar incidence of intraoperative hemodynamic disorders was recorded in both groups (hypotension p = 0.593; bradycardia p = 0.881). Neither PONV nor other complication was found. Patients in Group 1 reported a lower degree of interference with sleep (p = 0.001), less interference with daily activities (P = 0.002) and with the affective sphere (P = 0.015) along with a more satisfactory postoperative pain management (p < 0.001) as compared to Group 2. Conclusion: No significant differences were observed in the duration of motor and sensory blockade between patients in both groups. Additionally, both groups showed good pain control with a low rate of adverse effects, even if there was no clinical difference between the groups. However, patients who received dexamethasone reported experiencing less interference with their sleep, daily activities and overall emotional well-being, and overall pain control.

The Effect of a Subsequent Dose of Dexmedetomidine or Other Sedatives following an Initial Dose of Dexmedetomidine on Electrolytes, Acid-Base Balance, Creatinine, Glucose, and Cardiac Troponin I in Cats: Part II.

The administered dose of dexmedetomidine may occasionally fail to produce the anticipated sedative effects. Therefore, a subsequent dose or administration of another sedative may enhance sedation; however, patient safety may be affected. The safety of seven different drugs administered at the following time point after an insufficient dose of dexmedetomidine was evaluated in a crossover, blind, experimental study that included six healthy adult cats. All cats received an initial dose of dexmedetomidine and a subsequent dose of either dexmedetomidine (Group DD), NS 0.9% (DC), tramadol (DT), butorphanol (DBT), buprenorphine (DBP), ketamine (DK), or midazolam (DM). Animal safety was assessed using repeated blood gas analysis and measurement of electrolytes, glucose, cardiac troponin I, and creatinine to evaluate cardiac, respiratory, and renal function. The median values of creatinine, cardiac troponin I, pH, partial pressure of carbon dioxide, potassium, and sodium did not change significantly throughout the study. Heart rate was significantly decreased in all groups after administration of the drug combinations, except for in the DK group. Respiratory rate decreased significantly after administration of the initial dose of dexmedetomidine and in the DBP and DM groups. The partial pressure of oxygen, although normal, decreased significantly after the administration of dexmedetomidine, whereas the median concentration of glucose increased significantly following the administration of dexmedetomidine. The results of our study suggest that the drug combinations used did not alter the blood parameters above normal limits, while cardiac and renal function were not compromised. Therefore, a safe level of sedation was achieved. However, the administration of dexmedetomidine reduced the partial pressure of oxygen; thus, oxygen supplementation during sedation may be advantageous. Additionally, the increase in glucose concentration indicates that dexmedetomidine should not be used in cats with hyperglycaemia, whereas the decrease in haematocrit suggests that dexmedetomidine is not recommended in anaemic cats.

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.

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.

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.

Effects of dexmedetomidine on renal function after cardiac surgery for infective endocarditis: An interim analysis of a randomized controlled trial.

BACKGROUND: Patients undergoing cardiac surgery for infective endocarditis (IE) are at a high risk of postoperative acute kidney injury (AKI) owing to heightened systemic inflammation. Therefore, we aimed to investigate the effect of dexmedetomidine on postoperative AKI in patients who underwent cardiac surgery for IE. METHODS: A total of 63 patients who underwent cardiac surgery for IE were randomly assigned to receive either intravenous dexmedetomidine infusion of 0.4 µg kg-1 h-1 (DEX group) or normal saline infusion (control group) for 24 h after induction of anesthesia. The occurrence of AKI within seven days postoperation, epinephrine, norepinephrine, and interleukin-6 levels, as well as postoperative morbidities, were assessed. An intertrim analysis was conducted using Pocock's alpha spending function at α = 0.05 and ß = 0.2. RESULTS: This trial was early terminated according to the results of interim analysis performed when 60 % of the pre-set number of patients have been collected. The incidence of AKI was significantly lower in the DEX group than in the control group (32.3 % vs. 9.4 %, p = 0.025). Patients in the DEX group had significantly lower epinephrine levels than those in the control group, whereas norepinephrine and interleukin-6 levels were similar. Perioperative mean arterial pressure or heart rate did not differ between the groups. CONCLUSIONS: Dexmedetomidine administration for 24 h starting from induction of anesthesia significantly reduced the incidence of postoperative AKI after cardiac surgery for IE (by 29 % vs. control) without hemodynamic side effects. This was accompanied by a significant attenuation of postoperative increase in serum epinephrine levels.

[Updated ESAIC guidelines on postoperative delirium in adults]. / Aktualisierte ESAIC-Leitlinie zum postoperativen Delir beim Erwachsenen.

The updated ESAIC guideline on postoperative delirium (POD) comprises a total of 13 recommendations, including five with the recommendation grade "strong": 1.) The assessment of preoperative POD risk factors, 2.) the optimisation of the preoperative condition, 3.) the discussion of prevention strategies, 4) the implementation of a non-pharmacological multicomponent intervention in patients at risk of POD and 5.) the risk-benefit assessment of the prophylactic administration of dexmedetomidine. The latter applies in particular due to the partly contradictory data situation and different areas of application (cardiac surgery versus non-cardiac surgery patients). Index-based EEG monitoring of the depth of anaesthesia is also recommended, whereby other parameters such as burst suppression and density spectral array should also be included. If non-pharmacological measures fail, POD should be treated with haloperidol. In contrast, the use of benzodiazepines is not recommended.

Effect of epidural dexmedetomidine in single-dose combined with ropivacaine for cesarean section.

BACKGROUND: Dexmedetomidine has arousal sedation and analgesic effects. We hypothesize that epidural dexmedetomidine in single-dose combined with ropivacaine improves the experience of parturient undergoing cesarean section under epidural anesthesia. This study is to investigate the effect of 0.5 µg/kg epidural dexmedetomidine combined with epidural anesthesia (EA) in parturients undergoing cesarean section. METHODS: A total of 92 parturients were randomly divided into Group R (receiveing epidural ropivacaine alone) Group RD (receiveing epidural ropivacaine with 0.5 µg/kg dexmedetomidine). The primary outcome and second outcome will be intraoperative NRS pain scores and Ramsay Sedation Scale. RESULTS: All 92 parturients were included in the analysis. The NRS were significantly lower in Group RD compared to Group R at all observation timepoint (P > 0.05). Higher Ramsay Sedation Scale was found in Group RD compared to Group R (P < 0.001). No parturient has experienced sedation score of 4 and above. No significant difference regarding the incidence of hypotension, bradycardia and nausea or vomiting, Apgar scores and the overall satisfaction with anesthesia was found between Group R and Group RD (P > 0.05). CONCLUSION: Epidural dexmedetomidine of 0.5 µg/kg added slightly extra analgesic effect to ropivacaine in EA for cesarean section. The sedation of 0.5 µg/kg epidural dexmedetomidine did not cause mother-baby bonding deficit. Satisfaction with anesthesia wasn't significantly improved by epidural dexmedetomidine of 0.5 µg/kg. No additional side effect allows larger dose of epidural dexmedetomidine attempt. TRIAL REGISTRATION: This study was registered at www.chictr.org.cn (ChiCTR2000038853).

Association of dexmedetomidine use with haemodynamics, postoperative recovery, and cost in paediatric anaesthesia: a hospital registry study.

BACKGROUND: Dexmedetomidine utilisation in paediatric patients is increasing. We hypothesised that intraoperative use of dexmedetomidine in children is associated with longer postanaesthesia care unit length of stay, higher healthcare costs, and side-effects. METHODS: We analysed data from paediatric patients (aged 0-12 yr) between 2016 and 2021 in the Bronx, NY, USA. We matched our cohort with the Healthcare Cost and Utilization Project-Kids' Inpatient Database (HCUP-KID). RESULTS: Among 18 104 paediatric patients, intraoperative dexmedetomidine utilisation increased from 51.7% to 85.7% between 2016 and 2021 (P<0.001). Dexmedetomidine was dose-dependently associated with a longer postanaesthesia care unit length of stay (adjusted absolute difference [ADadj] 19.7 min; 95% confidence interval [CI]: 18.0-21.4 min; P<0.001, median length of stay of 122 vs 98 min). The association was magnified in children aged ≤2 yr undergoing short (≤60 min) ambulatory procedures (ADadj 33.3 min; 95% CI: 26.3-40.7 min; P<0.001; P-for-interaction <0.001). Dexmedetomidine was associated with higher total hospital costs of USD 1311 (95% CI: USD 835-1800), higher odds of intraoperative mean arterial blood pressure below 55 mm Hg (adjusted odds ratio [ORadj] 1.27; 95% CI: 1.16-1.39; P<0.001), and higher odds of heart rate below 100 beats min-1 (ORadj 1.32; 95% CI: 1.21-1.45; P<0.001), with no preventive effects on emergence delirium requiring postanaesthesia i.v. sedatives (ORadj 1.67; 95% CI: 1.04-2.68; P=0.034). CONCLUSIONS: Intraoperative use of dexmedetomidine is associated with unwarranted haemodynamic effects, longer postanaesthesia care unit length of stay, and higher costs, without preventive effects on emergence delirium.

Dexmedetomidine improves lung injury after one-lung ventilation in esophageal cancer patients by inhibiting inflammatory response and oxidative stress.

Aim: To explore the effect of Dexmedetomidine (DEX) on lung injury in patients undergoing One-lung ventilation (OLV). Methods: Esophageal cancer patients undergoing general anesthesia with OLV were randomly divided into the DEX group and control group, with 30 cases in each group. Mean arterial pressure (MAP), heart rate (HR), arterial partial pressure of oxygen (PO2), and arterial partial pressure of nitrogen dioxide (PCO2) were recorded at the time points after anesthesia induction and before OLV (T1), OLV 30 min (T2), OLV 60 min (T3), OLV 120 min (T4), OLV end before (T5) and before leaving the room (T6) in both groups. Reverse Transcription-Polymerase Chain Reaction (RT-qPCR) was applied to detect the levels of CC16 mRNA. Enzyme-linked immunosorbent assay (ELISA) was used to detect serum CC16 protein levels. The content of malondialdehyde (MDA) in serum was determined by thio barbituric acid (TBA) method. ELISA was used to measure the concentrations of TNF-α (tumor necrosis factor-alpha)/and IL-6 (interleukin 6). Results: DEX treatment slowed down HR at time points T1-T6 and increased PO2 and PCO2 at time points T2-T5 compared with the control group. Moreover, at time points T2-T6, DEX treatment reduced the levels of club cell secretory protein-16 (CC16) mRNA and serum CC16 protein levels. Furthermore, DEX treatment caused the reduction of MDA, TNF-α and IL-6 concentrations in serum of patients. Conclusion: During the OLV process, DEX could reduce serum CC16 protein levels, inhibit inflammatory reactions and oxidative stress, and improve oxygenation index, indicating a protective effect on lung injury during OLV.

Brain protective effect of dexmedetomidine vs propofol for sedation during prolonged mechanical ventilation in non-brain injured patients.

BACKGROUND: Dexmedetomidine and propofol are two sedatives used for long-term sedation. It remains unclear whether dexmedetomidine provides superior cerebral protection for patients undergoing long-term mechanical ventilation. AIM: To compare the neuroprotective effects of dexmedetomidine and propofol for sedation during prolonged mechanical ventilation in patients without brain injury. METHODS: Patients who underwent mechanical ventilation for > 72 h were randomly assigned to receive sedation with dexmedetomidine or propofol. The Richmond Agitation and Sedation Scale (RASS) was used to evaluate sedation effects, with a target range of -3 to 0. The primary outcomes were serum levels of S100-ß and neuron-specific enolase (NSE) every 24 h. The secondary outcomes were remifentanil dosage, the proportion of patients requiring rescue sedation, and the time and frequency of RASS scores within the target range. RESULTS: A total of 52 and 63 patients were allocated to the dexmedetomidine group and propofol group, respectively. Baseline data were comparable between groups. No significant differences were identified between groups within the median duration of study drug infusion [52.0 (IQR: 36.0-73.5) h vs 53.0 (IQR: 37.0-72.0) h, P = 0.958], the median dose of remifentanil [4.5 (IQR: 4.0-5.0) µg/kg/h vs 4.6 (IQR: 4.0-5.0) µg/kg/h, P = 0.395], the median percentage of time in the target RASS range without rescue sedation [85.6% (IQR: 65.8%-96.6%) vs 86.7% (IQR: 72.3%-95.3), P = 0.592], and the median frequency within the target RASS range without rescue sedation [72.2% (60.8%-91.7%) vs 73.3% (60.0%-100.0%), P = 0.880]. The proportion of patients in the dexmedetomidine group who required rescue sedation was higher than in the propofol group with statistical significance (69.2% vs 50.8%, P = 0.045). Serum S100-ß and NSE levels in the propofol group were higher than in the dexmedetomidine group with statistical significance during the first six and five days of mechanical ventilation, respectively (all P < 0.05). CONCLUSION: Dexmedetomidine demonstrated stronger protective effects on the brain compared to propofol for long-term mechanical ventilation in patients without brain injury.