The effect of sevoflurane exposure on cell-type-specific changes in the prefrontal cortex in young mice.

Sevoflurane, the predominant pediatric anesthetic, has been linked to neurotoxicity in young mice, although the underlying mechanisms remain unclear. This study focuses on investigating the impact of neonatal sevoflurane exposure on cell-type-specific alterations in the prefrontal cortex (PFC) of young mice. Neonatal mice were subjected to either control treatment (60% oxygen balanced with nitrogen) or sevoflurane anesthesia (3% sevoflurane in 60% oxygen balanced with nitrogen) for 2 hours on postnatal days (PNDs) 6, 8, and 10. Behavioral tests and single-nucleus RNA sequencing (snRNA-seq) of the PFC were conducted from PNDs 31 to 37. Mechanistic exploration included clustering analysis, identification of differentially expressed genes (DEGs), enrichment analyses, single-cell trajectory analysis, and genome-wide association studies (GWAS). Sevoflurane anesthesia resulted in sociability and cognition impairments in mice. Novel specific marker genes identified 8 distinct cell types in the PFC. Most DEGs between the control and sevoflurane groups were unique to specific cell types. Re-defining 15 glutamatergic neuron subclusters based on layer identity revealed their altered expression profiles. Notably, sevoflurane disrupted the trajectory from oligodendrocyte precursor cells (OPCs) to oligodendrocytes (OLs). Validation of disease-relevant candidate genes across the main cell types demonstrated their association with social dysfunction and working memory impairment. Behavioral results and snRNA-seq collectively elucidated the cellular atlas in the PFC of young male mice, providing a foundation for further mechanistic studies on developmental neurotoxicity induced by anesthesia.

Dexmedetomidine Infusion Versus Placebo During Light or Deep Anesthesia on Postoperative Delirium in Older Patients Undergoing Major Noncardiac Surgery: A Pilot Randomized Factorial Trial.

BACKGROUND: Postoperative delirium (POD) is common among older surgical patients and may be affected by dexmedetomidine and depth of anesthesia. We designed this pilot study to assess the feasibility of comparing dexmedetomidine with normal saline during light versus deep anesthesia on POD in older patients undergoing major noncardiac surgery. METHODS: In this pilot randomized factorial study, 80 patients aged 60 years or older undergoing major noncardiac surgery were randomized (1:1:1:1) to receive dexmedetomidine infusion 0.5 µg/kg/h or normal saline placebo during light (bispectral index [BIS] target 55) or deep (BIS target 40) anesthesia. Feasibility end points included consent rate and dropout rate, timely enrollment, blinded study drug administration throughout surgery, no inadvertent unmasking, achieving BIS target throughout >70% of surgery duration, and the process of twice-daily POD screening. In addition, we estimated the POD incidences in the 2 control groups (placebo and deep anesthesia) and treatment effects of dexmedetomidine and light anesthesia. RESULTS: Between November 1, 2021, and June 30, 2022, 78 patients completed the trial (mean [standard deviation, SD] age, 69.6 [4.6] years; 48 male patients [62%]; dexmedetomidine-deep, n = 19; dexmedetomidine-light, n = 20; placebo-deep, n = 19; placebo-light, n = 20). This study had a high consent rate (86%) and a low dropout rate (2.5%). Average recruitment was 5 patients at each center per month. Dexmedetomidine and normal saline were administered in a blinded fashion in all patients. Unmasking did not occur in either group. Approximately 99% of patients received the scheduled study drug infusion throughout the surgery. Approximately 81% of patients achieved the BIS targets throughout >70% of the surgery duration. The scheduled twice-daily POD screening was completed without exception. Overall, 10 of the 78 patients (13%; 95% confidence interval [CI], 7%-22%) developed POD. For the 2 reference groups, POD was observed in 7 of the 39 patients (17.9%; 95% CI, 9%-32.7%) in the placebo group and 7 of the 38 patients (18.4%; 95% CI, 9.2%-33.4%) in the deep anesthesia group. Regarding the treatment effects on POD, the estimated between-group difference was -10% (95% CI, -28% to 7%) for dexmedetomidine versus placebo, and -11% (95% CI, -28% to 6%) for light versus deep anesthesia. CONCLUSIONS: The findings of this pilot study demonstrate the feasibility of assessing dexmedetomidine versus placebo during light versus deep anesthesia on POD among older patients undergoing major noncardiac surgery, and justify a multicenter randomized factorial trial.

Comparison of opioid-free and opioid-inclusive propofol anaesthesia for thyroid and parathyroid surgery: a randomised controlled trial.

BACKGROUND: Postoperative nausea and vomiting occur frequently following thyroid and parathyroid surgery and are associated with worse patient outcomes. We hypothesised that opioid-free propofol anaesthesia would reduce the incidence of postoperative nausea and vomiting compared with opioid-inclusive propofol anaesthesia in patients undergoing these procedures. METHODS: We conducted a randomised, double-blinded controlled trial in adult patients scheduled to undergo thyroid and parathyroid surgery at two medical centres in mainland China. Patients were allocated randomly (1:1, stratified by sex and trial site) to an opioid-free anaesthesia group (esketamine, lidocaine, dexmedetomidine and propofol) or an opioid-inclusive group (sufentanil and propofol). Propofol infusions were titrated to bispectral index 45-55. Patients received prophylaxis for nausea and vomiting using dexamethasone and ondansetron and multimodal analgesia with paracetamol and flurbiprofen axetil. The primary outcome was the incidence of postoperative nausea and vomiting in the first 48 h after surgery. RESULTS: We assessed 557 patients for eligibility and 394 completed this trial. The incidence of postoperative nausea and vomiting in the first postoperative 48 h was lower in the opioid-free anaesthesia group (10/197, 5%) compared with opioid-inclusive group (47/197, 24%) (OR (95%CI) 0.17 (0.08-0.35), p < 0.001), yielding a number needed to treat of 5.3. Additionally, opioid-free propofol anaesthesia was associated with a reduced need for rescue anti-emetics, lower rates of hypotension and desaturation after tracheal extubation, and higher patient satisfaction. Time to tracheal extubation was prolonged slightly in the opioid-free group. The two groups had similar postoperative pain scores and 30-day outcomes. DISCUSSION: Opioid-free propofol anaesthesia reduced postoperative nausea and vomiting in patients undergoing thyroid and parathyroid surgery. An opioid-free anaesthetic regimen can optimise anaesthetic care during thyroid and parathyroid surgery.

Single-nucleus Atlas of Sevoflurane-induced Hippocampal Cell Type- and Sex-specific Effects during Development in Mice.

BACKGROUND: Multiple neonatal exposures to sevoflurane induce neurocognitive dysfunctions in rodents. The lack of cell type-specific information after sevoflurane exposure limits the mechanistic understanding of these effects. In this study, the authors tested the hypothesis that sevoflurane exposures alter the atlas of hippocampal cell clusters and have neuronal and nonneuronal cell type-specific effects in mice of both sexes. METHODS: Neonatal mice were exposed to 3% sevoflurane for 2 h at postnatal days 6, 8, and 10 and analyzed for the exposure effects at postnatal day 37. Single-nucleus RNA sequencing was performed in the hippocampus followed by in situ hybridization to validate the results of RNA sequencing. The Morris Water Maze test was performed to test neurocognitive function. RESULTS: The authors found sex-specific distribution of hippocampal cell types in control mice alongside cell type- and sex-specific effects of sevoflurane exposure on distinct hippocampal cell populations. There were important changes in male but not in female mice after sevoflurane exposure regarding the proportions of cornu ammonis 1 neurons (control vs. sevoflurane, males: 79.9% vs. 32.3%; females: 27.3% vs. 24.3%), dentate gyrus (males: 4.2% vs. 23.4%; females: 36.2% vs. 35.8%), and oligodendrocytes (males: 0.6% vs. 6.9%; females: 5.9% vs. 7.8%). In male but not in female mice, sevoflurane altered the number of significantly enriched ligand-receptor pairs in the cornu ammonis 1, cornu ammonis 3, and dente gyrus trisynaptic circuit (control vs. sevoflurane, cornu ammonis 1-cornu ammonis 3: 18 vs. 42 in males and 15 vs. 21 in females; cornu ammonis 1-dentate gyrus: 21 vs. 35 in males and 12 vs. 20 in females; cornu ammonis 3-dentate gyrus: 25 vs. 45 in males and 17 vs. 20 in females), interfered with dentate gyrus granule cell neurogenesis, hampered microglia differentiation, and decreased cornu ammonis 1 pyramidal cell diversity. Oligodendrocyte differentiation was specifically altered in females with increased expressions of Mbp and Mag. In situ hybridization validated the increased expression of common differentially expressed genes. CONCLUSIONS: This single-nucleus RNA sequencing study reveals the hippocampal atlas of mice, providing a comprehensive resource for the neuronal and nonneuronal cell type- and sex-specific effects of sevoflurane during development.

Remote Ischemic Preconditioning Reduces Acute Kidney Injury After Cardiac Surgery: A Systematic Review and Meta-analysis of Randomized Controlled Trials.

BACKGROUND: Results from previous studies evaluating the effects of remote ischemic preconditioning (RIPC) on morbidity and mortality after cardiac surgery are inconsistent. This meta-analysis of randomized controlled trials (RCTs) aims to determine whether RIPC improves cardiac and renal outcomes in adults undergoing cardiac surgery. METHODS: PubMed, EMBASE, and Cochrane Library were comprehensively searched to identify RCTs comparing RIPC with control in cardiac surgery. The coprimary outcomes were the incidence of postoperative myocardial infarction (MI) and the incidence of postoperative acute kidney injury (AKI). Meta-analyses were performed using a random-effect model. Subgroup analyses were conducted according to volatile only anesthesia versus propofol anesthesia with or without volatiles, high-risk patients versus non-high-risk patients, and Acute Kidney Injury Network (AKIN) or Kidney Disease Improving Global Outcomes (KDIGO) criteria versus other criteria for AKI diagnosis. RESULTS: A total of 79 RCTs with 10,814 patients were included. While the incidence of postoperative MI did not differ between the RIPC and control groups (8.2% vs 9.7%; risk ratio [RR] = 0.87, 95% confidence interval [CI], 0.76-1.01, P = .07, I2 = 0%), RIPC significantly reduced the incidence of postoperative AKI (22% vs 24.4%; RR = 0.86, 95% CI, 0.77-0.97, P = .01, I2 = 34%). The subgroup analyses showed that RIPC was associated with a reduced incidence of MI in non-high-risk patients, and that RIPC was associated with a reduced incidence of AKI in volatile only anesthesia, in non-high-risk patients, and in the studies using AKIN or KDIGO criteria for AKI diagnosis. CONCLUSIONS: This meta-analysis demonstrates that RIPC reduces the incidence of AKI after cardiac surgery. This renoprotective effect of RIPC is mainly evident during volatile only anesthesia, in non-high-risk patients, and when AKIN or KDIGO criteria used for AKI diagnosis.

Esketamine vs. placebo combined with erector spinae plane block vs. intercostal nerve block on quality of recovery following thoracoscopic lung resection: A randomized controlled factorial trial.

BACKGROUND: Multimodal analgesic strategy is pivotal for enhanced recovery after surgery. The objective of this trial was to assess the effect of subanesthetic esketamine vs. placebo combined with erector spinae plane block (ESPB) vs. intercostal nerve block (ICNB) on postoperative recovery following thoracoscopic lung resection. MATERIALS AND METHODS: This randomized, controlled, 2×2 factorial trial was conducted at a university hospital in Suzhou, China. One hundred adult patients undergoing thoracoscopic lung surgery were randomized to one of four groups (esketamine-ESPB, esketamine-ICNB, placebo-ESPB, and placebo-ICNB) to receive i.v. esketamine 0.3 mg/kg or normal saline placebo combined with ESPB or ICNB using 0.375% ropivacaine 20 mL. All patients received flurbiprofen axetil and patient-controlled fentanyl. The primary outcome was quality of recovery (QoR) at 24 h postoperatively, assessed using the QoR-15 scale, with a minimal clinically important difference of 6.0. RESULTS: The median age was 57 years and 52% were female. No significant interaction effect was found between esketamine and regional blocks on QoR (P=0.215). The QoR-15 score at 24 h was 111.5±5.8 in the esketamine group vs. 105.4±4.5 in the placebo group (difference=6.1, 95% CI, 4.0-8.1; P<0.001); 109.7±6.2 in the ESPB group vs. 107.2±5.6 in the ICNB group (difference=2.5, 95% CI, 0.2-4.9; P=0.033; not statistically significant after Bonferroni correction). Additionally, esketamine resulted in higher QoR-15 scores at 48 h (difference=4.6) and hospital discharge (difference=1.6), while ESPB led to a higher QoR-15 score at 48 h (difference=3.0). CONCLUSIONS: For patients undergoing thoracoscopic lung resection, subanesthetic esketamine improved QoR after surgery, while ICNB can be used interchangeably with ESPB as a component of multimodal analgesia.

Effect of Esketamine Added to Propofol Sedation on Desaturation and Hypotension in Bidirectional Endoscopy: A Randomized Clinical Trial.

Importance: Propofol sedation is widely used for endoscopic procedures, but it poses risks of hemodynamic and respiratory depression. The addition of esketamine as an adjuvant may reduce propofol requirements and associated adverse events. Objective: To evaluate the effects of low-dose esketamine added to propofol-based sedation on desaturation and hypotension during same-visit bidirectional endoscopy. Design, Setting, and Participants: This multicenter, double-blind, placebo-controlled randomized clinical trial assessed patients from 3 teaching hospitals in China who were scheduled for same-visit bidirectional endoscopy between February 8 and November 30, 2022, and randomly assigned to receive esketamine or normal saline (placebo). Interventions: After induction of sedation with 0.1 µg/kg of sufentanil and 0.5 mg/kg of propofol, patients in the esketamine group received 0.15 mg/kg of intravenous esketamine, whereas patients in the placebo group received an equivalent volume of saline. Sedation was achieved through propofol titration. Main Outcomes and Measures: The primary outcome was the composite of desaturation and hypotension during the procedures. Secondary outcomes included desaturation, hypotension, propofol requirements, postprocedure pain and fatigue, nausea or vomiting, dizziness or headache, hallucination or nightmare, endoscopist satisfaction, and patient satisfaction. Results: Among the 663 initially enrolled patients, 660 completed the study (median [IQR] age, 48 [36-57] years; 355 [53.8%] female), with 331 randomized to the esketamine group and 329 to the placebo group. The administration of esketamine compared with placebo significantly reduced the incidence of the composite outcome of desaturation and hypotension (8.2% vs 21.0%; difference, -12.8 percentage points; odds ratio [OR], 0.34; 95% CI, 0.21-0.54; P < .001). Additionally, esketamine led to significantly lower incidences of desaturation (OR, 0.36; 95% CI, 0.18-0.72; false discovery rate q = .01) and hypotension (OR, 0.33; 95% CI, 0.18-0.60; q < .001) and reduced propofol requirements (difference, -58.9 mg; 95% CI, -65.7 to -52.2 mg; q < .001), without significant effects on other secondary outcomes. Conclusions and Relevance: In this randomized clinical trial of patients undergoing same-visit bidirectional endoscopy, the administration of low-dose esketamine resulted in an approximately 61% reduction in the incidence of desaturation and hypotension, accompanied by decreased propofol requirements. These findings support the use of esketamine as an adjuvant to propofol-based sedation in endoscopic procedures. Trial Registration: Chinese Clinical Trial Registry Identifier: ChiCTR2200055938.

Effect of esketamine vs dexmedetomidine adjunct to propofol sedation for pediatric 3Tesla magnetic resonance imaging: a randomized, double-blind, controlled trial.

BACKGROUND: Adequate sedation is essential for pediatric patients undergoing 3Tesla (T) magnetic resonance imaging (MRI). Using propofol alone is associated with patient arousing and adverse airway events. This study aimed to assess esketamine vs dexmedetomidine adjunct to propofol sedation for pediatric 3 T MRI. METHODS: In this randomized, double-blind, controlled trial, 114 pediatric patients aged between 6 months and 8 years were randomly assigned, in a 1:1 ratio, to the esketamine-propofol group or the dexmedetomidine-propofol group. Sedation was provided with esketamine or dexmedetomidine in combination with propofol titration. The primary outcome was the total dose of propofol. Secondary outcomes included propofol infusion dose, adverse events, time to emergence from sedation, and time to discharge from recovery room. RESULTS: A total of 111 patients completed this study (56 in the esketamine-propofol group and 55 in the dexmedetomidine-propofol group). All MRI procedures were successfully performed under sedation. The total median (IQR) dose of propofol was significantly lower in the esketamine-propofol group (159.8 [121.7, 245.2] µg/kg/min) than that in the dexmedetomidine-propofol group (219.3 [188.6, 314.8] µg/kg/min) (difference in medians [95% CI] = - 66.9 [- 87.8 to - 43.0] µg/kg/min, P < 0.0001). The use of esketamine resulted in a lower dose of propofol for titration (difference in medians [95% CI] = - 64.3 [- 75.9 to - 51.9] µg/kg/min), a shorter time to emergence (difference in means [95% CI] = - 9.4 [- 11.4 to - 7.4] min), and a reduced time to recovery room discharge (difference in means [95% CI] = - 10.1 [- 12.1 to - 8.2] min). In the dexmedetomidine-propofol group, 2 patients experienced upper airway obstruction and 6 patients had bradycardia. No episodes of oxygen desaturation or other adverse events were observed. CONCLUSIONS: Although both regimens provided effective sedation for pediatric 3 T MRI, the esketamine-propofol sedation reduced propofol requirement and facilitated recovery, without detection of increased adverse effects in the studied population. Trial registration Chinese Clinical Trial Registry (identifier: ChiCTR2100048477).

Low-Dose Esketamine as an Adjuvant to Propofol Sedation for Same-Visit Bidirectional Endoscopy: Protocol for a Multicenter Randomized Controlled Trial.

Background: Same-visit bidirectional endoscopy (esophagogastroduodenoscopy and colonoscopy) is widely performed under sedation. At present, the optimal sedation regimen remains unclear. This study aims to test the hypothesis that a low-dose esketamine added to propofol sedation reduces hemodynamic and respiratory adverse events in these procedures. Methods: In this multicenter, randomized, double-blind, placebo-controlled trial, 660 adult patients scheduled for same-visit bidirectional endoscopy under sedation from 3 teaching hospitals in China will be recruited. Patients will be randomly allocated, in a 1:1 ratio, to an esketamine group or a normal saline group (n = 330 in each group), stratified by study center. All patients will receive intravenous propofol 0.5 mg/kg and sufentanil 0.1 µg/mL for induction of sedation, followed by intravenous esketamine 0.15 mg/kg or the same volume of normal saline. Propofol will be titrated to the target sedation levels during the procedures. The primary endpoint is a composite of desaturation (peripheral oxygen saturation < 90%) and hypotension (systolic blood pressure <80 mmHg or decrease >30% of baseline). Secondary endpoints include desaturation, hypotension, total dose of propofol, pain scores and fatigue scores on the 0-10 numerical rating scale, dizziness or headache, hallucination or nightmare, nausea or vomiting, endoscopist satisfaction, and patient satisfaction. All analyses will be intention-to-treat. Discussion: We expect that a low-dose esketamine adjunct to propofol-based sedation will improve cardiorespiratory stability in patients undergoing same-visit bidirectional endoscopy, providing reference for clinical sedation practice during these procedures. Trial Registration: Chinese Clinical Trial Registry (Identifier: ChiCTR-ChiCTR2200055938).

Dexmedetomidine Attenuates Ferroptosis-Mediated Renal Ischemia/Reperfusion Injury and Inflammation by Inhibiting ACSL4 via α2-AR.

Ischemia-reperfusion (I/R) injury is a serious clinical pathology associated with acute kidney injury (AKI). Ferroptosis is non-apoptotic cell death that is known to contribute to renal I/R injury. Dexmedetomidine (Dex) has been shown to exert anti-inflammatory and organ protective effects. This study aimed to investigate the detailed molecular mechanism of Dex protects kidneys against I/R injury through inhibiting ferroptosis. We established the I/R-induced renal injury model in mice, and OGD/R induced HEK293T cells damage in vitro. RNA-seq analysis was performed for identifying the potential therapeutic targets. RNA-seq analysis for differentially expressed genes (DEGs) reported Acyl-CoA synthetase long-chain family member 4 (ACSL4) related to ferroptosis and inflammation in I/R mice renal, which was validated in rodent renal. Liproxstatin-1, the specific small-molecule inhibitor of ferroptosis, significantly attenuated ferroptosis-mediated renal I/R injury with decreased LPO, MDA, and LDH levels, and increased GSH level. Inhibiting the activity of ACSL4 by the Rosiglitazone (ROSI) resulted in the decreased ferroptosis and inflammation, as well as reduced renal tissue damage, with decreasing LPO, MDA and LDH level, increasing GSH level, reducing COX2 and increasing GPx4 protein expression, and suppressing the TNF-α mRNA and IL-6 mRNA levels. Dex as a α2-adrenergic receptor (α2-AR) agonist performed renal protective effects against I/R-induced injury. Our results also revealed that Dex administration mitigated tissue damage, inhibited ferroptosis, and downregulated inflammation response following renal I/R injury, which were associated with the suppression of ACSL4. In addition, ACSL4 overexpression abolishes Dex-mediated protective effects on OGD/R induced ferroptosis and inflammation in HEK293T cells, and promotion of ACSL4 expression by α2-AR inhibitor significantly reversed the effects on the protective role of Dex. This present study indicated that the Dex attenuates ferroptosis-mediated renal I/R injury and inflammation by inhibiting ACSL4 via α2-AR.

Effect of Perioperative Dexmedetomidine on Delayed Graft Function Following a Donation-After-Cardiac-Death Kidney Transplant: A Randomized Clinical Trial.

Importance: Delayed graft function (DGF) is a risk factor for acute rejection and graft failure after kidney transplant. Previous studies have suggested that dexmedetomidine may be renoprotective, but whether the use of dexmedetomidine would improve kidney allograft function is unknown. Objective: To investigate the effects of perioperative dexmedetomidine on DGF following a donation-after-cardiac-death (DCD) kidney transplant. Design, Setting, and Participants: This single-center, double-blind, placebo-controlled randomized clinical trial was conducted at The First Affiliated Hospital of Soochow University in Suzhou, China. Adults (18 years or older) who were scheduled for DCD kidney transplant were enrolled between September 1, 2019, and January 28, 2021, and then randomized to receive either dexmedetomidine or normal saline (placebo). One-year postoperative outcomes were recorded. All analyses were based on the modified intention-to-treat population. Interventions: Patients who were randomized to the dexmedetomidine group received a 24-hour perioperative dexmedetomidine intravenous infusion (0.4 µg/kg/h intraoperatively and 0.1 µg/kg/h postoperatively). Patients who were randomized to the normal saline group received an intravenous infusion of the placebo with the same dose regimen as the dexmedetomidine. Main Outcomes and Measures: The primary outcome was the incidence of DGF, defined as the need for dialysis in the first posttransplant week. The prespecified secondary outcomes were in-hospital repeated dialysis in the first posttransplant week, in-hospital acute rejection, and serum creatinine, serum cystatin C, estimated glomerular filtration rate, need for dialysis, and patient survival on posttransplant day 30. Results: Of the 114 patients enrolled, 111 completed the study (mean [SD] age, 43.4 [10.8] years; 64 male patients [57.7%]), of whom 56 were randomized to the dexmedetomidine group and 55 to the normal saline group. Dexmedetomidine infusion compared with normal saline reduced the incidence of DGF (17.9% vs 34.5%; odds ratio [OR], 0.41; 95% CI, 0.17-0.98; P = .04) and repeated dialysis (12.5% vs 30.9%; OR, 0.32; 95% CI, 0.13-0.88; P = .02, which was not statistically significant after multiple testing corrections), without significant effect on other secondary outcomes. Dexmedetomidine vs normal saline infusion led to a higher median (IQR) creatinine clearance rate on postoperative days 1 (9.9 [4.9-21.2] mL/min vs 7.9 [2.0-10.4] mL/min) and 2 (29.6 [9.7-67.4] mL/min vs 14.6 [3.8-45.1] mL/min) as well as increased median (IQR) urine output on postoperative days 2 (106.5 [66.3-175.6] mL/h vs 82.9 [27.1-141.9] mL/h) and 7 (126.1 [98.0-151.3] mL/h vs 107.0 [82.5-137.5] mL/h) and at hospital discharge discharge (110.4 [92.8-121.9] mL/h vs 97.1 [77.5-113.8] mL/h). Three patients (5.5%) from the normal saline group developed allograft failure by the post hoc 1-year follow-up visit. Conclusions and Relevance: This randomized clinical trial found that 24-hour perioperative dexmedetomidine decreased the incidence of DGF after DCD kidney transplant. The findings support the use of dexmedetomidine in kidney transplants. Trial Registration: Chinese Clinical Trial Registry Identifier: ChiCTR1900025493.

Deep Neuromuscular Blockade Combined with Low Pneumoperitoneum Pressure for Nociceptive Recovery After Major Laparoscopic Gastrointestinal Surgery: Study Protocol for a Randomized Controlled Trial.

PURPOSE: Patients undergoing major laparoscopic surgery often experience significant pain and postoperative nausea and vomiting (PONV). Deep neuromuscular block (NMB) improves surgical conditions and facilitates the application of low intra-abdominal pressure (IAP), which may be beneficial for these patients. This study is designed to determine the effects of deep NMB combined with low IAP, as compared to moderate NMB combined with standard IAP, on patients' nociceptive recovery after major laparoscopic gastrointestinal surgery. STUDY DESIGN AND METHODS: This single-center randomized controlled trial will include 220 patients scheduled for major laparoscopic gastrointestinal surgery (lasts for ≥ 90 minutes). Patients will be randomly assigned, with a 1:1 ratio, into a deep NMB + low IAP group (train of four = 0, post-tetanic count = 1-3, IAP = 8 mmHg) and a moderate NMB + standard IAP group (train of four = 1-3, IAP = 12 mmHg). If the surgical workspace is inadequate, the surgeons can request a step increase of 1 mmHg in IAP during 3-min intervals. The upper limit of IAP will be set at 15 mmHg. Postoperative recovery will be assessed using the postoperative quality recovery scale (PQRS). The primary outcome of this trial is the PQRS nociceptive recovery (including pain and PONV) at postoperative day (POD) 1. The secondary outcomes include recovery in other PQRS domains at POD 1, and recovery in all PQRS domains in a post-anesthesia care unit, at POD 3 in the surgical wards, at hospital discharge, and at postoperative 30 days. For the sample size estimation, 110 patients in each group (220 in total) would be needed to detect an absolute increase rate of 20% in the PQRS nociceptive domain in the deep NMB + low IAP group at POD 1. DISCUSSION: This study investigates the effects of deep NMB combined with low IAP on postoperative PQRS nociceptive recovery in patients undergoing major laparoscopic gastrointestinal surgery. We expect that this deep NMB + low IAP strategy would improve postoperative pain and PONV following major laparoscopic gastrointestinal surgery.

Dexmedetomidine reduces acute kidney injury after endovascular aortic repair of Stanford type B aortic dissection: A randomized, double-blind, placebo-controlled pilot study.

STUDY OBJECTIVE: To determine the effect of dexmedetomidine on acute kidney injury (AKI) following endovascular aortic repair (EVAR) for Stanford type B aortic dissection (TBAD). DESIGN: Randomized, double-blind, placebo-controlled, pilot study. SETTING: University Hospital. PATIENTS: 102 TBAD patients undergoing EVAR procedures were enrolled. Patients with dissection involving aortic arch or renal artery were excluded. INTERVENTIONS: Patients were randomly assigned, in a 1:1 ratio, to a dexmedetomidine group (intravenous dexmedetomidine 0.4 µg/kg/h immediately after anesthesia induction and 0.1 µg/kg/h after extubation, which was maintained until 24 h) or a normal saline control group. MEASUREMENTS: The primary outcome was the incidence of AKI within the first two days after surgery, based on the Acute Kidney Injury Network (AKIN) criteria. The secondary outcomes included serum cystatin C and estimated glomerular filtration rate on postoperative days 1, 2, and 7, and in-hospital need for renal replacement therapy (RRT). Long-term outcomes included RRT and all-cause mortality. MAIN RESULTS: Ninety-eight patients completed the study (dexmedetomidine, n = 48; control, n = 50). AKIN stage 1 AKI occurred in 3/48 (6.3%) patients receiving dexmedetomidine, compared with 11/50 (22%) patients receiving normal saline (odds ratio = 0.24, 95% CI: 0.07 to 0.89, P = 0.041). This difference remained significant after adjusting for baseline covariates (adjusted odds ratio = 0.21, 95% CI: 0.05 to 0.84; P = 0.028). Dexmedetomidine led to a lower serum cystatin C on postoperative day 1 (median [IQR] mg/L: 1.31 [1.02-1.72] vs. 1.58 [1.28-1.96]). There were no between-group differences in other secondary or long-term outcomes. During the follow-up (median = 28.4 months), 1 patient in the dexmedetomidine group and 3 patients in the control group required RRT. CONCLUSIONS: Dexmedetomidine reduced the incidence of AKI in TBAD patients after EVAR procedures. The long-term benefits of dexmedetomidine in this patient population warrant further investigation. TRIAL REGISTRATION: ChiCTR-IPR-15006372.

Withholding vs. Continuing Angiotensin-Converting Enzyme Inhibitors or Angiotensin Receptor Blockers Before Non-cardiac Surgery in Older Patients: Study Protocol for a Multicenter Randomized Controlled Trial.

Background: Older hypertensive adults are at increased risk for postoperative morbidity and mortality. As first line antihypertensive drug therapy, angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin receptor blockers (ARBs) have many beneficial effects. However, the use of ACEIs/ARBs in the perioperative period remains controversial. This study aims to determine the effects of withholding vs. continuing ACEIs/ARBs before non-cardiac surgery on perioperative hypotension and postoperative outcomes in older patients. Methods: In this multicenter, randomized, double-blind, placebo-controlled trial, a total of 2036 patients aged 60-80 years undergoing non-cardiac surgical procedures will be randomly assigned, in a 1:1 ratio, to receive oral ACEIs/ARBs (the ACEIs/ARBs continued group) or inactive placebos (the ACEIs/ARBs withheld group) on the morning of surgery. For both groups, the ACEIs/ARBs will be continued from the first postoperative day. The primary outcome measure is the incidence of perioperative hypotensive events, defined as mean blood pressure (MBP) < 65 mmHg or ≥30% reduction in MBP from baseline during surgery and in a post-anesthesia care unit. The secondary outcomes include duration of perioperative hypotension, intraoperative use of fluids and vasopressors, hypotensive events within postoperative 3 days, and perioperative neurocognitive disorders, major adverse cardiocerebral events (a composite outcome of stroke, coma, myocardial infarction, heart block, and cardiac arrest), and mortality within 30 days after surgery. Discussion: The results of this trial will offer an evidence-based perioperative ACEIs/ARBs therapy for older hypertensive adults undergoing non-cardiac surgery. Study Registration: This study is approved by the Medical Ethics Committee of The First Affiliated Hospital of Soochow University (Approval No. 2020-077-1) and by the institutional ethics review board of each participating center. This protocol is registered at the Chinese Clinical Trials Registry (ChiCTR2000039376).