Programmed death of cardiomyocytes in cardiovascular disease and new therapeutic approaches.

Cardiovascular diseases (CVDs) have a complex pathogenesis and pose a major threat to human health. Cardiomyocytes have a low regenerative capacity, and their death is a key factor in the morbidity and mortality of many CVDs. Cardiomyocyte death can be regulated by specific signaling pathways known as programmed cell death (PCD), including apoptosis, necroptosis, autophagy, pyroptosis, and ferroptosis, etc. Abnormalities in PCD can lead to the development of a variety of cardiovascular diseases, and there are also molecular-level interconnections between different PCD pathways under the same cardiovascular disease model. Currently, the link between programmed cell death in cardiomyocytes and cardiovascular disease is not fully understood. This review describes the molecular mechanisms of programmed death and the impact of cardiomyocyte death on cardiovascular disease development. Emphasis is placed on a summary of drugs and potential therapeutic approaches that can be used to treat cardiovascular disease by targeting and blocking programmed cell death in cardiomyocytes.

Opioid-free anaesthesia reduces postoperative nausea and vomiting after thoracoscopic lung resection: a randomised controlled trial.

BACKGROUND: Intraoperative opioid use has a positive relationship with postoperative nausea and vomiting (PONV), and opioid-free anaesthesia (OFA) might reduce PONV. We investigated whether OFA compared with opioid-based anaesthesia would reduce PONV during the first 2 postoperative days among patients undergoing thoracoscopic lung resection. METHODS: In this randomised controlled trial, 120 adult patients were randomly assigned (1:1, stratified by sex) to receive either OFA with esketamine, dexmedetomidine, and sevoflurane, or opioid-based anaesthesia with sufentanil and sevoflurane. A surgical pleth index (SPI) of 20-50 was applied for intraoperative analgesia provision. All subjects received PONV prophylaxis (dexamethasone and ondansetron) and multimodal analgesia (flurbiprofen axetil, ropivacaine wound infiltration, and patient-controlled sufentanil). The primary outcome was the occurrence of PONV during the first 48 h after surgery. RESULTS: The median age was 53 yr and 66.7% were female. Compared with opioid-based anaesthesia, OFA significantly reduced the incidence of PONV (15% vs 31.7%; odds ratio [OR]=0.38, 95% confidence interval [CI], 0.16-0.91; number needed to treat, 6; P=0.031). Secondary and safety outcomes were comparable between groups, except that OFA led to a lower rate of vomiting (OR=0.23, 95% CI, 0.08-0.77) and a longer length of PACU stay (median difference=15.5 min, 95% CI, 10-20 min). The effects of OFA on PONV did not differ in the prespecified subgroups of sex, smoking status, and PONV risk scores. CONCLUSIONS: In the context of PONV prophylaxis and multimodal analgesia, SPI-guided opioid-free anaesthesia halved the incidence of PONV after thoracoscopic lung resection, although it was associated with a longer stay in the PACU. CLINICAL TRIAL REGISTRATION: Chinese Clinical Trial Registry (ChiCTR2200059710).

The Effect of Dexmedetomidine as a Local Anesthetic Adjuvant for Iliac Fascia Compartment Block on Postoperative Delirium in Elderly Patients Undergoing Elective Hip Surgery.

INTRODUCTION: We analyzed the effect of dexmedetomidine (DEX) as a local anesthetic adjuvant on postoperative delirium (POD) in elderly patients undergoing elective hip surgery. METHODS: In this study, 120 patients undergoing hip surgery were enrolled and randomly assigned to two groups: fascia iliaca compartment block with DEX + ropivacaine (the Y group, n = 60) and fascia iliaca compartment block with ropivacaine (the R group, n = 60). The primary outcomes: presence of delirium during the postanesthesia care unit (PACU) period and on the first day (D1), the second day (D2), and the third day (D3) after surgery. The secondary outcomes: preoperative and postoperative C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR), occurrence of insomnia on the preoperative day, day of operation, D1 and D2; HR values of patients in both groups before iliac fascia block (T1), 30 min after iliac fascia block (T2), at surgical incision (T3), 20 min after incision (T4), when they were transferred out of the operating room (T5) and after leaving the recovery room (T6) at each time point; VAS for T1, PACU, D1, D2; the number of patients requiring remedial analgesics within 24 h after blockade and related complications between the two groups. RESULTS: A total of 97 patients were included in the final analysis, with 11 and 12 patients withdrawing from the R and Y groups, respectively. The overall incidence of POD and its incidence in the PACU and ward were all lesser in the Y group than in the R group (p < 0.05). Additionally, fewer cases required remedial analgesia during the PACU period, and more vasoactive drugs were used for maintaining circulatory system stability in the Y group as compared to the R group (p < 0.05). At the same time, the incidence of intraoperative and postoperative bradycardia in the Y group was higher than that in the R group, accompanied by lower postoperative CRP and ESR (all p < 0.05). CONCLUSION: Ultrasound-guided high fascia iliaca compartment block with a combination of ropivacaine and DEX can reduce the incidence of POD, the use of intraoperative opioids and postoperative remedial analgesics, and postoperative inflammation in elderly patients who have undergone hip surgery, indicating that this method could be beneficial in the prevention and treatment of POD.

Dexmedetomidine and magnesium sulfate in preventing junctional ectopic tachycardia after pediatric cardiac surgery.

BACKGROUND: Junctional ectopic tachycardia (JET) is a serious tachyarrhythmia following pediatric cardiac surgery. It isn't easy to treat and better to be prevented. This study aimed to examine the prophylactic effects of dexmedetomidine, MgSO4, or their combination in reducing JET following pediatric open cardiac surgery. METHODS: Hundred and twenty children under 5 years, weighing more than 5 kg, who were scheduled for corrective acyanotic cardiac surgeries were randomized into three groups. Group MD (Dexmedetomidine-MgSO4 group): received dexmedetomidine 0.5 µg/kg IV over 20 min after induction, then infusion 0.5 µg/kg/h for 72 h, and 50 mg/kg bolus of MgSO4 with aortic cross-clamp release, then continued administration for 72 h postoperatively at a dose of 30 mg/kg/day. Group D (the dexmedetomidine group) received the same dexmedetomidine as the MD group in addition to normal saline instead of MgSO4. Group C (control group): received normal saline instead of dexmedetomidine and MgSO4. The primary outcome was the detection of JET incidence; the secondary outcomes were hemodynamic parameters, ionized Mg, vasoactive-inotropic score, extubation time, PCCU and hospital stay, and perioperative complications. RESULTS: The incidence of JET was significantly reduced in Group MD and Group D (p = .007) compared to Group C. Ionized Mg was significantly higher in Group MD than in Groups D and C during rewarming and in the ICU (p < .001). Better hemodynamic profile in Group MD compared to Group D and Group C throughout surgery and in the ICU, the predictive indexes were significantly better in Group MD than in Groups D and C (p < .001). Including the extubation time, PCCU, and hospital stay. CONCLUSION: Dexmedetomidine alone or combined with MgSO4 had a therapeutic role in the prevention of JET in children after congenital heart surgery.

Future Directions in Optimizing Anesthesia to Reduce Perioperative Acute Kidney Injury.

BACKGROUND: Perioperative acute kidney injury (AKI) is common in surgical patients and is associated with high morbidity and mortality. There are currently few options for AKI prevention and treatment. Due to its complex pathophysiology, there is no efficient medication therapy to stop the onset of the injury or repair the damage already done. Certain anesthetics, however, have been demonstrated to affect the risk of perioperative AKI in some studies. The impact of anesthetics on renal function is particularly important as it is closely related to the prognosis of patients. Some anesthetics can induce anti-inflammatory, anti-necrotic, and anti-apoptotic effects. Propofol, sevoflurane, and dexmedetomidine are a few examples of anesthetics that have protective association with AKI in the perioperative period. SUMMARY: In this study, we reviewed the clinical characteristics, risk factors, and pathogenesis of AKI. Subsequently, the protective effects of various anesthetic agents against perioperative AKI and the latest research are introduced. KEY MESSAGE: This work demonstrates that a thorough understanding of the reciprocal effects of anesthetic drugs and AKI is crucial for safe perioperative care and prognosis of patients. However, more complete mechanisms and pathophysiological processes still need to be further studied.

Dexmedetomidine for the prevention of delirium in adults admitted to the intensive care unit or post-operative care unit: A systematic review of randomised clinical trials with meta-analysis and Trial Sequential Analysis.

OBJECTIVES: To assess any benefit or harm, we conducted a systematic review of randomised clinical trials (RCTs) allocating adults to dexmedetomidine versus placebo/no intervention for the prevention of delirium in intensive care or post-operative care units. DATA SOURCES: We searched Medline, Embase, CENTRAL and other databases. The last search was 9 April 2022. DATA EXTRACTION: Literature screening, data extraction and risk of bias volume 2 assessments were performed independently and in duplicate. Primary outcomes were occurrences of serious adverse events (SAEs), delirium and all-cause mortality. We used meta-analysis, Trial Sequential Analysis, and GRADE (Grading Recommendations Assessment, Development and Evaluation). DATA SYNTHESIS: Eighty-one RCTs (15,745 patients) provided data for our primary outcomes. Results from trials at low risk of bias showed that dexmedetomidine may reduce the occurrence of the most frequently reported SAEs (relative risk [RR] 0.69; 95% CI 0.43-1.09), cumulated SAEs (RR 0.70; 95% CI 0.52-0.95) and the occurrence of delirium (RR 0.62; 95% CI 0.43-0.89). The certainty of evidence was very low for delirium. Mortality was very low in trials at low risk of bias (0.4% in the dexmedetomidine groups and 1.0% in the control groups) and meta-analysis did not provide conclusive evidence that dexmedetomidine may result in lower or higher all-cause mortality (RR 0.47; 95% CI 0.18-1.21). There was a lack of information from trial results at low risk of bias for all primary outcomes. CONCLUSIONS: Trial results at low risk of bias showed that dexmedetomidine might reduce occurrences of SAEs and delirium, while no conclusive evidence was found for effects on all-cause mortality. The certainty of evidence ranged from very low for occurrence of delirium to low for the remaining outcomes.

The preventive effect of dexmedetomidine on anesthesia complications in strabismus surgery: a systematic review and meta-analysis.

OBJECTIVE: Dexmedetomidine is a medication that has analgesic, sedative, and anti-anxiety properties. In the clinical, it is often used to prevent common complications associated with strabismus surgery, including postoperative delirium, postoperative nausea and vomiting, postoperative pain, and oculocardiac reflex. However, its effectiveness and side effects of the present studies are different. The sample sizes of the present studies on the prevention of complications of dexmedetomidine are small. Therefore, this study evaluates the efficacy of dexmedetomidine in preventing anesthesia-related complications in strabismus surgery through a systematic review and meta-analysis. METHODS: Literature was retrieved from 10 commonly used databases and randomized controlled trials published up to May 2022 were sought. The included studies compared the intervention effects of dexmedetomidine versus placebo on anesthesia-related complications in surgery. The occurrence rates of postoperative delirium, postoperative nausea and vomiting, postoperative pain, and oculocardiac reflex in patients undergoing strabismus surgery were evaluated. Statistical analyses and forest plots were generated using Review Manager and STATA software. Binary outcomes were measured using relative risk (RR) with a 95% confidence interval for each outcome. The Cochrane risk of bias tool was used to assess the bias and risk in the studies that met the inclusion criteria. RESULTS: A total of 13 articles were ultimately included in the analysis, comprising 1,018 patients who underwent strabismus surgery. The dexmedetomidine group, compared to the placebo group, demonstrated significant reductions in the incidence of postoperative delirium (RR = 0.73, P = 0.001), severe postoperative delirium (RR = 0.45, P = 0.005), postoperative nausea and vomiting (RR = 0.48, P < 0.0001), and the need for supplemental analgesia postoperatively (RR = 0.60, P = 0.004). Additionally, subgroup analysis revealed that intravenous administration of dexmedetomidine significantly reduced the incidence of oculocardiac reflex (RR = 0.50, P = 0.001). In contrast, intranasal administration of dexmedetomidine did not have a significant effect on the incidence of oculocardiac reflex (RR = 1.22, P = 0.15). There was a significant difference between the subgroups (P = 0.0005, I2 = 91.7%). CONCLUSION: Among patients undergoing strabismus surgery, the use of dexmedetomidine can alleviate postoperative delirium and reduce the incidence of postoperative nausea and vomiting, as well as postoperative pain. Moreover, intravenous administration of dexmedetomidine can lower the occurrence rate of the oculocardiac reflex.

The role of dexmedetomidine as an adjuvant for high-thoracic erector spinae plane block for analgesia in shoulder arthroscopy; a randomized controlled study.

BACKGROUND: Management of postoperative pain after shoulder arthroscopy is an important issue. Dexmedetomidine, as an adjuvant, improves nerve block efficacy and decreases postoperative consumption of opioids. As a result, we designed this study to determine if adding dexmedetomidine to an erector spinae plane block (ESPB) that is guided by ultrasound (US) is beneficial for treating immediate postoperative pain following shoulder arthroscopy. METHODS: This randomized controlled double-blind trial recruited 60 cases 18-65 years old of both sexes, American Society of Anesthesiologists (ASA) physical status I-II, scheduled for elective shoulder arthroscopy. Random allocation of 60 cases was done equally into two groups according to the solution injected in US-guided ESPB at T2 before general anesthetic induction. Group (ESPB): 20 ml 0.25% bupivacaine. Group (ESPB + DEX): 19 ml bupivacaine 0.25% + 1 mL dexmedetomidine 0.5 µg/kg. The primary outcome was The total rescue morphine consumption in the first 24 postoperative hours. RESULTS: The mean intraoperative fentanyl consumption was significantly lower in the group (ESPB + DEX) compared to the group (ESPB) (82.86 ± 13.57 versus 100.74 ± 35.07, respectively, P = 0.015). The median (IQR) time of the 1st rescue analgesic request was significantly delayed in the group (ESPB + DEX) compared to group (ESPB) [18.5 (18.25-18.75) versus 12 (12-15.75), P = 0.044]. The number of cases that required morphine was significantly lower in the group (ESPB + DEX) than in the group (ESPB) (P = 0.012). The median (IQR) of total postoperative morphine consumption in 1st 24 h was significantly lower in the group (ESPB + DEX) compared to the group (ESPB) [0 (0-0) versus 0 (0-3), P = 0.021]. CONCLUSION: The dexmedetomidine as an adjuvant to bupivacaine in ESPB produced adequate analgesia by reducing the intraoperative and postoperative opioid requirements in shoulder arthroscopy. TRIAL REGISTRATION: This study is registered on ClinicalTrials.gov (NCT05165836; principal investigator: Mohammad Fouad Algyar; registration date: 21/12/ 2021).

Effect of erector spinae plane block with different doses of dexmedetomidine as adjuvant for ropivacaine on the postoperative quality of recovery after video-assisted thoracoscopic lobectomy surgery: a randomized controlled trial.

BACKGROUND: Erector spinae plane block (ESPB) improves postoperative analgesia and significantly enhances the quality of recovery (QoR) after video-assisted thoracoscopic lobectomy surgery (VATLS). However, it is not known whether the use of dexmedetomidine (Dex) as an adjunct for ropivacaine to ESPB affects the QoR after VATLS. The purpose of this study was to explore the effects of different Dex dosages as an adjunct for ropivacaine in combination with ultrasound-guided ESPB on the quality of postoperative recovery in patients with VATLS. METHODS: In this single-center, double-blind, randomized study, 120 patients between the ages of 18 and 65 who were scheduled for VATLS from december 2021 and october 2022 in our hospital under general anesthesia were randomly divided into three groups: ultrasound-guided ESPB with 30 mL of 0.5% ropivacaine (Group R), ultrasound-guided ESPB 0.5% ropivacaine plus 0.5 µg/kg Dex (Group RD1), and ultrasound-guided ESPB 0.5% ropivacaine plus 1.0 µg/kg Dex (Group RD2), ultrasound-guided ESPB was administrated at the T5 vertebral level before surgery. The primary outcome was the QoR-15 score 24 h after the surgery. The secondary outcomes included the QoR-15 scores at 12 h, 48 h, and 72 h after the operation, visual analogue scale (VAS) scores at 8 h, 12 h, 24 h, and 48 h after surgery, cumulative flurbiprofen consumption, postoperative nausea and vomiting (PONV), postoperative bradycardia, and hypotension. RESULTS: The QoR-15 scores were higher in group RD2 than the R and RD1 groups on postoperative day 1 (P < 0.05), in addition, no significant difference was found in the QoR-15 scores between groups R and RD1 on postoperative day 1. The VAS scores were significantly lower in group RD2 than in groups RD1 and group R 12-24 h after surgery (P < 0.05). No significant differences were observed in the QoR-15 and VAS scores at 48 and 72 h after surgery between the three groups. The cumulative flurbiprofen consumption was markedly reduced during the 72 h after surgery in the RD2 group (P < 0.05). The incidence of postoperative nausea and vomiting was lower in the RD2 group (P < 0.05). CONCLUSIONS: The combination of 1 µg/kg dexmedetomidine as an adjunct with 0.5% ropivacaine 30 ml for erector spinae plane block significantly improved the postoperative quality of recovery and provided better postoperative analgesia on postoperative day 1 in patients undergoing Video-assisted thoracoscopic lobectomy surgery. However, dexmedetomidine (1 µg/kg) as an adjunct for ropivacaine combined with erector spinae plane block did not enhance the postoperative quality of recovery at 48 and 72 h postoperatively. TRIAL REGISTRY NUMBER: The number of this clinical trial registry is ChiCTR2100053230, date of registration: 16/11/ 2021).

Postoperative analgesic effect of dexmedetomidine combined with TPVB applied to open gastrectomy for gastric cancer.

OBJECTIVES: This study is aimed to investigate the analgesic effect of combined dexmedetomidine and thoracic paravertebral nerve block (TPVB) on gastric cancer (GC) patients undergoing open gastrectomy. METHODS: From May 2019 to Nov 2020, a total of 80 GC patients preparing for open gastrectomy were enrolled in our hospital and were divided into the ropivacaine (RO) group and the ropivacaine + dexmedetomidine (RD) group ad libitum. All of the patients underwent TPVB. The characteristics, usage of patient-controlled analgesia (PCA), adverse events, visual analogue scale (VAS) scores, inflammatory cytokines, and T cell subgroups between the two groups were compared. RESULTS: Patients in the RD group showed the decreased occurrence rate of postoperative adverse events and VAS scores and improved anti-inflammation and immune function. These findings implied that the application of dexmedetomidine in combination with RO in TPVB has a good postoperative analgesic effect, as well as anti-inflammatory and immune-enhancing effects. CONCLUSIONS: Dexmedetomidine as an adjunct analgesic may be potentially applied in clinical practice for GC patients undergoing open gastrectomy.

Dexmedetomidine as a cardioprotective drug: a narrative review.

Dexmedetomidine (DEX), a highly selective alpha2-adrenoceptors agonist, is not only a sedative drug used during mechanical ventilation in the intensive care unit but also a cardio-protective drug against ischemia-reperfusion injury (IRI). Numerous preclinical in vivo and ex vivo studies, mostly evaluating the effect of DEX pretreatment in healthy rodents, have shown the efficacy of DEX in protecting the hearts from IRI. However, whether DEX can maintain its cardio-protective effect in hearts with comorbidities such as diabetes has not been fully elucidated. Multiple clinical trials have reported promising results, showing that pretreatment with DEX can attenuate cardiac damage in patients undergoing cardiac surgery. However, evidence of the post-treatment effects of DEX in clinical practice remains limited. In this narrative review, we summarize the previously reported evidence of DEX-induced cardio-protection against IRI and clarify the condition of the hearts and the timing of DEX administration that has not been tested. With further investigations evaluating these knowledge gaps, the use of DEX as a cardio-protective drug could be further facilitated in the management of patients undergoing cardiac surgery and might be considered in a broader area of clinical settings beyond cardiac surgery, including patients with acute myocardial infarction.

Analgesic Effects of Ropivacaine Combined With Dexmedetomidine in Transversus Abdominis Plane Block in Patients Undergoing Laparoscopic Cholecystectomy: A Systematic Review and Meta-Analysis.

PURPOSE: This review aimed to conduct a meta-analysis of published randomized controlled studies (RCTs) comparing the effectiveness of dexmedetomidine (DEX) combined with ropivacaine versus single ropivacaine in transversus abdominis plane block (TAPB) for postoperative analgesia after laparoscopic cholecystectomy (LC). The purpose was to investigate whether DEX combined with ropivacaine in TAPB for postoperative analgesia in LC is superior to single ropivacaine administration. DESIGN: A Systematic Review and Meta-analysis. METHODS: Five electronic database systems were searched for RCTs on the effects of DEX combined with ropivacaine (joint group) and single ropivacaine on postoperative analgesia in LC. The standardized mean difference (SMD) or odds ratio (OR) and their corresponding 95% confidence interval (CI) of the indicators were calculated for comparison. FINDINGS: As of December 23, 2021, 153 articles were retrieved, but only 16 articles were finally included in this meta-analysis. The results showed that compared with single ropivacaine, DEX combined with ropivacaine in TAPB had better analgesia and lighter sedative effect in patients after LC. After LC 2h(T1), 4h(T2), 8h(T3), 12h(T4) and 24h (T5), the joint group participants have lower VAS scores (T1: SMD = -0.32, 95%CI: -0.49, -0.14; T2: SMD = -1.11, 95%CI: -1.56, -0.65; T3: SMD = -2.88, 95%CI: -3.74, -2.02; T4: SMD = -2.56, 95%CI: -3.04, -2.08; T5: SMD = -1.44, 95%CI: -1.81, -1.06). Also, the Ramsay score of the joint group is higher than the single group (T1: SMD = 1.05, 95%CI: 0.39, 1.71; T2: SMD = 1.57, 95%CI: 0.57, 2.57; T3: SMD = 1.64, 95%CI: 0.65, 2.63; T4: SMD = 1.72, 95%CI: 0.54, 2.89; T5: SMD = 0.57, 95%CI: 0.21, 0.94). CONCLUSIONS: The results of this review and meta-analysis suggest that DEX combined with ropivacaine has less postoperative pain, more patients got the status of sober and cooperative, and longer postoperative analgesia lasted than ropivacaine alone in TAPB, especially in the group of combined treatment with 1.0 mcg/kg DEX. Furthermore, the flow dynamics of the two groups are stable, and there is no notable difference in the incidence of adverse reactions.

Dexmedetomidine modulates mitochondrial dynamics to protect against endotoxin-induced lung injury via the protein kinase C-ɑ/haem oxygenase-1 signalling pathway.

BACKGROUND: Endotoxin-induced acute lung injury (ALI) has a high mortality rate, and there are limited effective treatment options available. The aim of the present study was to identify if dexmedetomidine could regulate mitochondrial fusion and fission through the protein kinase C (PKC)-α/haem oxygenase (HO)-1 pathway to protect against endotoxin-induced ALI. MATERIALS AND METHODS: Dexmedetomidine was administered by intraperitoneal injection once daily for three days prior to induction of lung injury to mice. Mice in the PKC-α inhibitor group received dexmedetomidine by intraperitoneal injection 1 h after each chelerythrine injection, and lipopolysaccharide was injected 1 h after the last dose of dexmedetomidine. The lung wet/dry weight ratio, oxidative stress, inflammatory response, and expression levels of PKC-α, Nrf2, HO-1, Mfn1, Mfn2, OPA1, Drp1, and Fis1 were determined. RESULTS: Dexmedetomidine administration attenuated lung oxidative stress, decreased inflammatory cytokines secretion, and downregulated the expression levels of Drp1 and Fis1. Moreover, dexmedetomidine increased levels of Mfn1, Mfn2, and OPA1, and alleviated endotoxin-induced lung injury. Administration of chelerythrine partially reversed the pneumoprotective effects of dexmedetomidine. CONCLUSIONS: Dexmedetomidine may activate the PKC-ɑ/HO-1 pathway to increase the expression of Mfn1, Mfn2, and OPA1, while decreasing Drp1 and Fis1 expression, thereby reduce endotoxin-induced acute lung injury.

The Safety and Efficacy Evaluation of Dexmedetomidine for Procedural Sedation and Postoperative Behaviors in Pediatric Populations: A Systematic Review and Meta-analysis.

BACKGROUND: This study systematically evaluated the safety and efficacy of dexmedetomidine for procedural sedation and postoperative behaviors in a pediatric population as well as whether the results met the information required to draw conclusions. OBJECTIVE: To evaluate the safety and efficacy evaluation of dexmedetomidine for procedural sedation and postoperative behaviors in a pediatric population. METHODS: PubMed, Cochrane library, Web of Science and Ovid MEDLINE were searched to obtain randomized controlled trials (RCTs) comparing dexmedetomidine with control medicine and comparing different doses of dexmedetomidine. RESULTS: There were a total of 16 RCTs for a total of 3240 patients. Dexmedetomidine slowed down the heart rate (HR; mean difference: -13.27; 95% CI: -16.41 to 10.14; P < 0.001) and reduced postoperative delirium (risk ratio [RR]: 0.31; 95% CI: 0.20-0.50; P < 0.001), the number of pain patients (RR: 0.48; 95% CI: 0.30-0.75; P = 0.002), and desaturation (RR: 0.34; 95% CI: 0.13-0.89; P = 0.03) compared with the control group. The limitation was that it was difficult to determine the range of low- and high-dose dexmedetomidine. CONCLUSION AND RELEVANCE: Dexmedetomidine slowed down intraoperative HR within the normal range, which might reduce myocardial oxygen consumption. It reduced postoperative pain and postoperative complications: delirium and desaturation. Dexmedetomidine showed no dose-dependent increase in the procedural sedation time of pediatric patients. Clinically, dexmedetomidine can improve pediatric procedural sedation and postoperative behavior, and it can be considered as a related medicine for safety in pediatric surgery.

Efficacy of dexmedetomidine as an adjunct to ropivacaine in bilateral dual-transversus abdominis plane blocks in patients with ovarian cancer who underwent cytoreductive surgery.

OBJECTIVE: We sought to evaluate the postoperative control of pain and recovery in patients with ovarian cancer who underwent cytoreductive surgery by adding dexmedetomidine to ropivacaine in bilateral dual-transversus abdominis plane (Bd-TAP) blocks. METHODS: We enrolled 90 patients with an American Society of Anesthesiologists physical status I to III undergoing open abdominal cytoreductive surgery in this study. Patients were randomized and assigned into three groups (TAP-R, TAP-DR, or CON) of 30 participants each. All of the patients received standardized general anesthesia, and postoperative Bd-TAP blocks were performed. The TAP-R, TAP-DR, and CON groups received Bd-TAP blocks with 0.3% ropivacaine, 0.3% ropivacaine and 0.5 µg/kg of dexmedetomidine, and 0.9% normal saline, respectively. All of the patients received patient-controlled analgesia (PCA) (formula, 100 µg of sufentanil and 16 mg of ondansetron diluted with normal saline to 100 mL). Flurbiprofen axetil was used as a rescue drug if the visual analog scale (VAS) score was more than four points. The first request time for PCA bolus; the VAS scores at 0, 6, 12, 24, and 48 h after operation; and the cumulative sufentanil consumption within 24 and 48 h, respectively, were compared. Pulmonary function was evaluated preoperatively and at 24 h after the operation. The use of the rescue drug was recorded. Postoperative functional recovery, including time to stand, time to walk, time to return of bowel function, time to readiness for discharge, and postoperative complications, were recorded. RESULTS: Median values of the first request time for PCA of the TAP-R group was significantly prolonged compared to that of the CON group (median [interquartile range], 7.3 [6.5-8.0] hours vs. 3.0 [2.3-3.5] hours) (P < .001), while the TAP-DR group has the longest request time among the three groups (median [interquartile range], 13.5 [12.4-14.5] hours) (P < .001). The VAS scores at rest and upon coughing of the TAP-R group in the first 12 h were significantly lower than those of the CON group (P < 0.05), but showed no significant difference compared to those of the TAP-DR group. The VAS scores at rest and upon coughing were lower in the TAP-DR group at each time point compared to those of the CON group (P < .05). The cumulative sufentanil consumption in the TAP-DR group was significantly lower at 48 h (P = .04) after surgery than in the CON group, while there was no significant difference compared to that in the TAP-R group (P > .05). Less rescue analgesic was required by patients in the TAP-DR group than in the CON group (P < .05). Postoperative mean measured forced expiratory volume in 1 s (FEV1) and FEV1/forced vital capacity values in the TAP-DR group were significantly higher than those of the CON group (P = .009), while there was no significant difference compared to those of the TAP-R group (P = .10). There was no significantly difference in postoperative functional recovery between TAP-DR and CON group (P > 0.05). CONCLUSION: TAP blocks can provide effective pain relief up to 12 h postoperatively without a significant improvement in postoperative pulmonary function. The addition of dexmedetomidine to ropivacaine for Bd-TAP block prolonged the first bolus time of PCA when compared to that in the TAP-R group and decreased sufentanil consumption and the need of rescue analgesia relative to in the CON group at 48 h postoperative. The procedure provided better postoperative analgesia and improved postoperative pulmonary function relative to the CON group. Our results indicate that dexmedetomidine as an adjuvant of Bd-TAP can provide effective pain relief up to 48 h.

Opioid-free anesthesia compared to opioid anesthesia for laparoscopic radical colectomy with pain threshold index monitoring: a randomized controlled study.

BACKGROUND: Few studies have investigated the depth of intraoperative analgesia with non-opioid anesthesia. This study evaluated whether opioid-free anesthesia can provide an effective analgesia-antinociception balance monitored by the / pain threshold index in laparoscopic radical colectomy. METHODS: We enrolled 102 patients undergoing laparoscopic radical colectomy with general anesthesia. Participants were randomly allocated into two groups to receive opioid-free anesthesia (group OFA) with dexmedetomidine (loading dose with 0.6 µg·kg-1 for 10 min and then 0.5 µg·kg-1·h-1 continuous infusion) and sevoflurane plus bilateral paravertebral blockade (0.2 µg·kg-1 dexmedetomidine and 0.5% ropivacaine 15 ml per side) or opioid-based anesthesia (group OA) with remifentanil, sevoflurane, and bilateral paravertebral blockade (0.5% ropivacaine 15 ml per side). The primary outcome variable was pain intensity during the operation, as assessed by the pain threshold index with the multifunction combination monitor HXD- I. Results were analyzed using repeated measures analysis of variance and Student's t-test. The secondary outcomes were wavelet index, lactic levels, and blood glucose concentration during the operation. The visual analog scale (VAS), rescue analgesic consumption, and side-effects of opioids after surgery were further assessed. RESULTS: One hundred and one patients were included in the analysis. Analysis revealed that the intraoperative pain threshold index readings were not significantly different between the groups from incision to the end of the operation (P = 0.06). Furthermore, similar changes in the brain wavelet index readings were observed in the OFA and OA groups. There was no statistical difference in VAS scores between the groups (P > 0.05); however, non-opioid anesthesia did reduce the rescue analgesic consumption after operation (P < 0.05). In the OFA group, the blood glucose levels increased by 20% compared to baseline and were significantly higher than those in the OA group (P < 0.001). The incidences of postoperative nausea and vomiting, urine retention, intestinal paralysis and pruritus were not significantly different from those in the OA group (P > 0.05). CONCLUSIONS: This study suggests that compared to the opioid anesthesia regimen, our opioid-free anesthesia regimen achieved an equally effective intraoperative pain threshold index in laparoscopic radical colectomy. The incidence of opioid-related adverse reactions was not different between regimens, and intraoperative blood glucose levels were higher with opioid-free anesthesia. TRIAL REGISTRATION: ChiCTR1900021223, 02/02/2019, Title: " Opioid-free anesthesia in laparoscopic surgery: a randomized controlled trial ". Website: hppts:// www.chictr.ogr.cn.

The effect of dexmedetomidine on renal function after surgery: A systematic review and meta-analysis.

WHAT IS KNOWN AND OBJECTIVE: Acute kidney injury (AKI) is a complication following surgery and has been associated with worsened patient outcomes. Providers have used agents that may confer a degree of renal protection in the perioperative stage. Such is the case of dexmedetomidine, a selective alpha-2 adrenergic agonist used in the intensive care unit (ICU) as a sedative agent. The primary objective of this meta-analysis was to characterize the use of dexmedetomidine and to evaluate its impact on renal markers and outcomes in patients after surgery. METHODS: A systematic review of manuscripts was performed to identify patients who received dexmedetomidine after surgery by searching the PubMed, Embase, and Cochrane databases. The following parameters were captured: blood urea nitrogen (BUN), serum creatinine, creatinine clearance, neutrophil gelatinase-associated lipoprotein (NGAL), cystatin C, urine output, duration of mechanical ventilation, ICU length of stay, AKI, need for dialysis, and mortality. RESULTS AND DISCUSSION: Nineteen studies with 3,395 patients were included in the analyses. The mean bolus and infusion dose of dexmedetomidine were 0.82 µg/kg and 0.54 mcg/kg/hr, respectively. There was a significant difference in creatinine clearance and NGAL in favour of the dexmedetomidine group. In addition, the dexmedetomidine group had a shorter ICU length of stay, and a lower risk of acute kidney injury and mortality compared to the control. There was no difference in the rest of the parameters. WHAT IS NEW AND CONCLUSION: Dexmedetomidine appears to have postoperative renal protective effects. This is evidenced by lower NGAL levels and increased creatinine clearance in those who received dexmedetomidine. These effects are associated with decreases in ICU length of stay and risk of AKI and mortality.

Combined femoral and popliteal nerve block is superior to local periarticular infiltration anaesthesia for postoperative pain control after total knee arthroplasty.

INTRODUCTION: After primary total knee arthroplasty (TKA), local periarticular infiltration anaesthesia (LIA) is a fast and safe method for postoperative pain control. Moreover, ultrasound-guided regional anaesthesia (USRA) with femoral and popliteal block is a standard procedure in perioperative care. Two analgesic regimens for TKA-LIA versus URSA with dexmedetomidine-were compared as an additive to ropivacaine. We hypothesised that the use of URSA provides a superior opioid sparing effect for TKA compared with LIA. METHODS: Fifty patients (planned 188 participants; safety analysis was performed after examining the first 50 participants) were randomised. These patients received LIA into the knee capsule during surgery with 60 ml of ropivacaine 0.5% and 1 ml of dexmedetomidine (100 µg ml-1) or two single-shot URSA blocks (femoral and popliteal block) before surgery with 15 ml of ropivacaine 0.5% and 0.5 ml of dexmedetomidine for each block. Postoperative opioid consumption in the first 48 h, pain assessment and complications were analysed. RESULTS: In the safety analysis, there was a significantly higher need for opioids in the LIA group, with a median oral morphine equivalent of 42.0 [interquartile range (IQR) 23.5-57.0] mg versus 27.0 [IQR 0.0-33.5] mg (P = 0.022). Due to this finding, the study was terminated for ethical considerations according to the protocol. CONCLUSION: This is the first study presenting data on LIA application in combination with dexmedetomidine. A superior opioid-sparing effect of URSA was observed when compared with LIA in TKA when dexmedetomidine is added to local anaesthetics. Also, a longer lasting opioid-sparing effect in the LIA group was observed when compared with the recently published literature; this difference could be attributed to the addition of dexmedetomidine. Therefore, multimodal analgesia regimens could be further improved when LIA or USRA techniques are combined with dexmedetomidine.

Effect of dexmedetomidine for prevention of acute kidney injury after cardiac surgery: an updated systematic review and meta-analysis.

BACKGROUND: Acute kidney injury (AKI) is a serious complication related to cardiac surgery. Several studies have been conducted to investigate the effect of dexmedetomidine administration on AKI prevention. OBJECTIVE: To assess if dexmedetomidine is associated with a protective effect of renal function after cardiac surgery. And the aim of conducting this meta-analysis is to summarize the literature and determine the clinical utility of dexmedetomidine administration in patients undergoing cardiac surgery. METHODS: PubMed, Cochrane Library, and EMBASE databases were comprehensively searched for all randomized controlled trials (RCTs) published before 1 December, 2021 that investigated the effect of dexmedetomidine on AKI prevention. RESULTS: Our analysis included 16 studies involving 2148 patients. Compared with the control group, dexmedetomidine administration significantly reduced AKI incidence (OR, 0.47; 95% CI, 0.36-0.61; p < 0.00001; I2 = 26%) and the length of stay in the intensive care unit (ICU) but did not alter mortality rate, length of stay in the hospital, and mechanical ventilation time. Furthermore, the incidence of delirium among patients treated with dexmedetomidine was significantly decreased. CONCLUSION: Dexmedetomidine administration has a positive effect on preventing AKI and postoperative delirium after cardiac surgery and significantly reduces the length of stay in the ICU.

Effects of Dexmedetomidine on Patients Undergoing Laparoscopic Surgery for Colorectal Cancer.

BACKGROUND: Pneumoperitoneum during laparoscopic surgery has a systemic impact on the renal system and might contribute to acute kidney injury or postoperative renal dysfunction. However, effective preventive strategies are still lacking. We aimed to explore the effects of dexmedetomidine (DEX) on kidney and other organ function in patients undergoing elective laparoscopic surgery for colorectal cancer. MATERIALS AND METHODS: Fifty-six patients were randomly enrolled into the Control or DEX group. The DEX group received 1 µg kg-1 DEX intravenously within 10 min followed by a maintenance dose of 0.5 µg kg-1 h-1 infused until 30 min before closing the peritoneum. In the Control group, 0.9% sodium chloride was administered as a placebo. The primary outcome was serum neutrophil gelatinase-associated lipocalin (NGAL) levels reflecting kidney injury. Secondary outcomes included variables reflecting the kidney, intestinal injury and systemic inflammatory response. RESULTS: NGAL levels were significantly lower in the DEX group than in the Control group at 1 d and 5 d postoperatively (107.5 ± 55.6 ng mL-1versus 179.5 ± 78.2 ng mL-1; 70.3 ± 45.8 ng mL-1versus 135.2 ± 59.6 ng mL-1, P < 0.001), while the BUN and Cr levels showed no differences between the groups. Serum DAO activity was significantly lower in the DEX group patients 24 h after surgery. Moreover, I-FABP levels were markedly lower at 2 h and 24 h postoperatively in the DEX group than in the Control group (P < 0.001). CONCLUSIONS: Perioperative DEX administration may potentially confer kidney and intestinal protection during laparoscopic surgery for colorectal cancer patients.