Efficacy and safety of esketamine hydrochloride adjunct to sufentanil in non-surgical patients under mechanical ventilation in the ICU (SENSATION trial): protocol for a multicentre, single-blind, randomised controlled trial.

INTRODUCTION: Pain is common in patients receiving mechanical ventilation in the intensive care unit (ICU). Intravenous opioids are recommended as first-line therapy for pain management; however, opioids have adverse side effects. Based on low-quality evidence, low-dose ketamine is therefore recommended as an opioid adjunct to reduce opioid consumption. Esketamine is an alternative to ketamine with greater efficacy and fewer side effects. However, evidence on the use of esketamine in patients receiving mechanical ventilation is lacking. This study investigates the efficacy and safety of esketamine as an adjunct to sufentanil for analgesic therapy in non-surgical ICU patients under mechanical ventilation. METHODS AND ANALYSIS: This ongoing multicentre, single-blind, randomised controlled trial is being conducted at six ICUs in China. 132 non-surgical patients under mechanical ventilation will be randomly assigned to the standard care and S-ketamine groups at a 1:1 ratio. Patients in the standard care group received a minimal dose of sufentanil as the sole analgesic agent. Patients in the S-ketamine group received a minimal dose of sufentanil in addition to an esketamine infusion at a fixed rate of 0.2 mg/kg/hour for analgesia. The primary outcome is mean hourly sufentanil consumption during the treatment period. ETHICS AND DISSEMINATION: This study was approved by the Ethics Committee of Chongqing University Cancer Hospital (CZLS2022067-A). Participants are required to provide informed consent. The results of this trial will be reported in peer-reviewed journals and presented at conferences. TRIAL REGISTRATION NUMBER: ChiCTR2200058933.

Can Multimodal Analgesia Reduce Postoperative Opioid Consumption in Patients Undergoing Shoulder Arthroscopy? A Retrospective Study.

AIM: The aim of this study was to investigate whether multimodal analgesia can decrease postoperative opioid usage in patients undergoing shoulder arthroscopy. METHODS: Patients diagnosed with subacromial impingement syndrome who underwent acromioplasty at our institution between October 2022 and November 2023 were retrospectively analyzed. Patients were divided into an observation group and a control group based on postoperative pain management methods. The control group received intravenous self-controlled electronic analgesia (sufentanil injection 1 µg/kg + butorphanol injection 4 mg + 0.9% NaCl injection to 100 mL), while the observation group received multimodal analgesia (ropivacaine subacromial pump 3 mL/h, combined with oral celecoxib and acetaminophen). Visual Analog Scale (VAS) scores were recorded preoperatively and at various postoperative time points, and opioid usage, length of hospital stay, and analgesia-related complications within 1 week postoperatively were compared between groups. The 36-item Short Form Health Survey (SF-36) scores and the Constant-Murley score (CMS), were also assessed 1 day and 1 week after treatment. RESULTS: One hundred thirty-two patients were included in the study, 66 in the observation group and 66 in the control group. In the control group, there were 46 males and 20 females, with a mean age of 55.47 ± 11.42 years and in the observation group 44 males and 22 females, with a mean age of 56.13 ± 12.19 years The observation group consistently reported significantly lower pain intensity compared to the control group at 8 h (T1), 24 (T2), and 48 h (T3) after surgery (p < 0.05). Additionally, the observation group exhibited significantly lower opioid usage and complication rates compared to the control group (p < 0.05). SF-36 scores and CMS scores were significantly higher in the observation group 1 week after treatment compared to the control group (p < 0.05). CONCLUSIONS: Following shoulder arthroscopy, multimodal analgesia effectively reduces opioid consumption, lowers complication rates, and provides effective short-term pain relief. This approach carries significant implications for improving patient outcomes.

Sublingual sufentanil tablet system (SSTS) versus a single shot peri-nervous injection of ropivacaine for the management of postoperative pain after total knee arthroplasty: a single-center randomized trial.

INTRODUCTION: For several years, ropivacaine has been the standard-of-care for establishing postoperative femoral nerve block in total knee arthroplasty (TKA) setting and is still widely in use but new approaches such as the patient-controlled administration of sublingual sufentanil tablets system (SSTS) seem to offer good clinical results. Our aim is to compare the SSTS to single shot peri-nervous injection of ropivacaine (single shot) after TKA in terms of effectiveness in pain management and of time to recovery. MATERIALS AND METHODS: A total of 165 patients undergoing TKA were enrolled. Eighty-four patients were randomly allocated in the SSTS group and 81 patients in the single shot group. The primary objective of the study was to evaluate performance of Timed Up and Go test. Secondary objectives were to measure the length of stay, NRS pain scale, the adherence to the prescribed plan, the joint mobility, the frequency of rescue analgesic use, side effects and patients' satisfaction. RESULTS: Of all patients of the single shot group, 64 were withdrawn from the study as they unable to achieve pain control; only one patient was withdrawn from the SSTS group. Times for the "Timed Up and Go" test on the 3rd postoperative day were 8.4 ± 1.6 and 11.8 ± 3.6 in the SSTS group (n = 83) and single shot group (n = 17), respectively (p < .001). CONCLUSIONS: SSTS provides better pain management when compared to peri-nervous ropivacaine single shot injection after TKA.

The influence of COMT and ABCB1 gene polymorphisms on sufentanil analgesic effect for postoperative pain in children with fracture.

The aim of this observational study was to investigate the effects of catechol-O-methyltransferase (COMT) and ATP-binding cassette transporter B1 (ABCB1) gene polymorphisms on the postoperative analgesic effect of sufentanil in Chinese Han pediatric patients with fractures. A total of 185 pediatric patients who underwent fracture surgery were included. Polymerase chain reaction-restriction fragment length polymorphism was used to detect the polymorphisms of COMT and ABCB1 genes. Sufentanil was used for postoperative analgesia. The pain level of the patients was evaluated using the face, legs, activity, cry, and consolability scale before surgery, during awakening, at 2, 6, 12, and 24 hours after surgery. The postoperative Ramsay sedation score, sufentanil consumption, and incidence of adverse reactions were also recorded. Pediatric patients with different genotypes of ABCB1 and COMT showed no statistically significant differences in general data such as age, gender, weight, height, surgical duration, and American Society of Anesthesiologists classification (P > .05). There were no statistically significant differences in sedation scores after surgery between different genotypes of ABCB1 and COMT (P > .05). Among patients with CC genotype in ABCB1, the pain scores and total consumption of sufentanil at awakening, 2 and 6 hours after surgery were higher compared to TT and CT genotypes (P < .05), while there were no statistically significant differences between TT and CT genotypes (P > .05). Among patients with AA genotype in COMT, the pain scores and total consumption of sufentanil at awakening, 2, 6, 12, and 24 hours after surgery were higher compared to AG and GG genotypes (P < .05), while there were no statistically significant differences between AG and GG genotypes (P > .05). There were no statistically significant differences in adverse reactions between different genotypes of ABCB1 and COMT (P > .05). The polymorphisms of COMT gene rs4680 and ABCB1 gene rs1045642 are associated with the analgesic effect and consumption of sufentanil in pediatric patients after fracture surgery.

Randomized clinical trial of continuous transversus thoracis muscle plane block for patients undergoing open heart valve replacement surgery.

The optimal analgesia regimen after open cardiac surgery is unclear. The aim of this study was to investigate the beneficial effects of continuous transversus thoracis muscle plane (TTMP) blocks initiated before surgery on open cardiac surgery outcomes. A group of 110 patients were randomly allocated to either receive bilateral continuous TTMP blocks (TTP group) or no nerve block (SAL group). The primary endpoint was post-operative pain at 4, 8, 16, 24, 48 and 72 h after extubation at rest and exercise. The secondary outcome measures included analgesia requirements (sufentanil and flurbiprofen axetil administration), time to extubation, incidence of reintubation, length of stay in the ICU, incidence of post-operative nausea and vomiting (PONV), time until return of bowel function, time to mobilization, urinary catheter removal and length of hospital stay. The length of stay in the ICU and length of hospital stay were significantly longer in the SAL group than in the TTP group. NRS scores at rest and exercise were significantly lower in the TTP group than in the SAL group at all time points. The TTP group required significantly less intraoperative and post-operative sufentanil and post-operative dynastat consumption than the SAL group. Time to extubation, time to first flatus, time until mobilization and time until urinary catheter removal were significantly earlier in the TTP group than in the SAL group. The incidence of PONV was significantly lower in the TTP group. Bilateral continuous TTMP blocks provide effective analgesia and accelerate recovery in patients undergoing open heart valve replacement surgery.

Comparison of the analgesic effect of dezocine and esketamine in combination with sufentanil respectively after laparoscopic cholecystectomy: a prospective randomized controlled study.

BACKGROUND: Sufentanil in combination with dezocine or esketamine is often used for postoperative analgesia. However, there is a lack of clinical evidence of efficacy. This study compares the analgesic effects of esketamine and dezocine combined with sufentanil for relieving pain after laparoscopic cholecystectomy(LC). METHODS: A total of 58 patients were randomly assigned to the esketamine group (ES group) and dezocine group (DE group). In the ES group, 1.5 mg/kg esketamine was used. In the DE group, 0.3 mg/kg dezocine was used. Primary outcome measures were Visual Analog Scale (VAS) score at 4 h, 8 h, 24 h and 48 h after surgery. The second outcome measures were Interleukin-6 (IL-6) and C-reactive protein (CRP) levels in the serum 10 minutes before anesthesia induction, and at 24 h and 48 h after surgery. RESULTS: The VAS scores at 4 h, 8 h, 24 h and 48 h after the surgery in the ES group vs DE group were 2.70 vs 3.50(P=0.013),2.35 vs 3.15(P=0.004),1.69 vs 2.58(P=0.002), and 1.50 vs 2.26(P=0.002), respectively. The serum IL-6 concentrations 10 minutes before anesthesia induction, and at 24 h and 48 h after surgery in the ES group and DE group were 34.39 and 34.12(P=0.901),112.33 and 129.60(P=0.014), and 89.69 and 108.46(P<0.001), respectively. The CRP levels in serum 10 minutes before anesthesia induction, and at 24 h and 48 h after the surgery in the ES group and DE group were 5.99 and 5.86(P=0.639), 28.80 and 35.37(P<0.001), and 23.17 and 30.11(P<0.001), respectively. CONCLUSION: For postoperative pain after LC, 1.5mg/kg esketamine provided better analgesia and reduced inflammation levels than 0.3mg/kg dezocine. TRIAL REGISTRATION: This trial was registered in the China Clinical Research Information Center in 31/05/2023 : https://www.chictr.org.cn/bin/home (Registration number: ChiCTR2300072011).

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).

Effect of magnesium sulfate perioperative infusion on postoperative catheter-related bladder discomfort in male patients undergoing laparoscopic radical resection of gastrointestinal cancer: a prospective, randomized and controlled study.

BACKGROUND: Laparoscopic radical resection of gastrointestinal cancer is associated with a high incidence of postoperative catheter-related bladder discomfort (CRBD). Studies on the benefits of magnesium sulfate intravenous infusion during the perioperative period post-laparoscopic surgery are yet lacking. METHODS: A total of 88 gastrointestinal cancer male patients scheduled for laparoscopic radical resection were randomly divided into two groups: normal saline (control) and magnesium. In the magnesium group, a 40 mg/kg loading dose of intravenous magnesium sulfate was administered for 10 min just after the induction of anesthesia, followed by continuous intravenous infusion of 15 mg/kg/h magnesium sulfate until the end of the surgery; the control group was administered the same dose of normal saline. Subsequently, 2 µg/kg sufentanil was continuously infused intravenously by a postoperative patient-controlled intravenous analgesia (PCIA) device. The primary outcome was the incidence of CRBD at 0 h after the surgery. The secondary outcomes included incidence of CRBD at 1, 2, and 6 h postsurgery, the severity of CRBD at 0, 1, 2, and 6 h postsurgery. Remifentanil requirement during surgery, sufentanil requirement within 24 h postsurgery, the postoperative numerical rating scale (NRS) score at 48 h after the surgery, magnesium-related side effects and rescue medication (morphine) requirement were also assessed. RESULTS: The incidence of CRBD at 0, 1, 2, and 6 h postoperatively was lower in the magnesium group than the control group (0 h: P = 0.01; 1 h: P = 0.003; 2 h: P = 0.001; 6 h: P = 0.006). The incidence of moderate to severe CRBD was higher in the control group at postoperative 0 and 1 h (0 h: P = 0.002; 1 h: P = 0.028), remifentanil requirement during surgery were significantly lower in the magnesium group than the control group. Sufentanil requirements during the 24 h postoperative period were significantly lower in the magnesium group than the control group. The NRS score was reduced in the magnesium group compared to the control group in the early postoperative period. Magnesium-related side effects and rescue medication (morphine) did not differ significantly between the two groups. CONCLUSIONS: Intravenous magnesium sulfate administration reduces the incidence and severity of CRBD and remifentanil requirement in male patients undergoing radical resection of gastrointestinal cancer. Also, no significant side effects were observed. TRIAL REGISTRATION: Chictr.org.cn ChiCTR2100053073. The study was registered on 10/11/2021.

Application of Butorphanol versus Sufentanil in Multimode Analgesia via Patient Controlled Intravenous Analgesia After Hepatobiliary Surgery: A Retrospective Cohort Study.

Purpose: We investigate the efficacy and safety of butorphanol in multimodal analgesia combined with dexmedetomidine and ketorolac via patient-controlled intravenous analgesia (PCIA) after hepatobiliary surgery, as compared with sufentanil. Patients and Methods: Postoperative follow-up data of hepatobiliary surgery patients in Henan Provincial People's Hospital from March 2018 to June 2021 were collected retrospectively and divided into butorphanol group (group B) or sufentanil group (group S) according to the postoperative intravenous controlled analgesia scheme. The baseline characteristics and surgical information of the two groups were matched through propensity score matching (PSM). Results: A total of 3437 patients were screened, and PSM yielded 1816 patients after matching, including 908 in the butorphanol group and 908 in the sufentanil group. Compared with group S, the incidence of moderate-to-severe pain on the first postoperative day and the second postoperative day was lower in group B during rest (3.2% vs 10.9%, P<0.001; 1.2% vs 4.6%, P<0.001), and during movement (7.0% vs 18.9%, P<0.001; 2.6% vs 8.7%, P<0.001). Patients receiving butorphanol had a lower morphine consumption (50mg vs 120mg, P<0.001). The bolus attempts of an analgesic pump in group B were significantly lower than in group S (1 vs 2, P<0.001). Postoperative hospital length of stay was shortened in group B (11d vs 12d, P=0.017). The occurrence of postoperative vomiting was lower in group B (1.4% vs 3.0%, P=0.025) than in group S. However, more patients in group B experienced dizziness (0.9% vs 0.1%, P=0.019). Conclusion: Compared with sufentanil, the application of butorphanol in multimodal analgesia combined with dexmedetomidine and ketorolac via PCIA ameliorated postoperative pain after hepatobiliary surgery, with reduced opioid consumption and shorter postoperative hospital length of stay.

The Median Effective Volume of 0.375% Ropivacaine for Ultrasound-guided Anterior Suprascapular Nerve Block in Arthroscopic Shoulder Surgery.

BACKGROUND: The suprascapular nerve (SSN) is an important nerve that contributes to shoulder joint sensation and movement. The anterior suprascapular nerve block (aSSNB) has the potential for noninferior analgesic effect compared with the interscalene block while preserving respiratory function. This study investigated the median effective volume (MEV) of 0.375% ropivacaine in aSSNB for analgesic effect among patients undergoing arthroscopic shoulder surgery. OBJECTIVES: Our primary objective was the MEV. The secondary objectives included the 24 hour sufentanil consumption, 24 hour patient-controlled analgesia (PCA) presses, and incidences of diaphragm impairment. STUDY DESIGN: Prospective registered (ChiCTR2300070129), single-armed, volume-finding study. SETTING: This study was conducted in a tertiary, single center. METHODS: There were 23 patients who completed the study. Using an up-and-down process, patients enrolled in the study received different volumes of 0.375% ropivacaine for an aSSNB adjusted based on the success or failure of the previous patient in the study's block by increasing or decreasing the volume by 3 mL. The first patient received 15 mL of 0.375% ropivacaine. The nerve blocks were evaluated by the sensory score of the C5 and C6 dermatomes. RESULTS: MEV50 (50% of the patients) was 6 mL (95% CI, 5.78 - 6.78 mL), and MEV95 (95% of the patients) was 13.88 mL (95% CI, 13.37 - 14.87 mL). There was no significant difference in the PCA presses, 24 hour sufentanil consumption, and incidences of diaphragm impairments between successful and unsuccessful blocks. LIMITATIONS: Our study focused on the analgesic effect rather than hemi-diaphragmatic paralysis with 0.375% ropivacaine for an aSSNB. The study also did not test varying ropivacaine concentrations while keeping the volume constant. Further investigation with varying concentrations and a larger sample size is indicated to address the optimal volume and concentration to balance analgesia and diaphragm function. CONCLUSIONS: To produce effective analgesic effect, the MEV50 is 6 mL, and the MEV95 is 13.88 mL in patients undergoing arthroscopic shoulder surgery who receive an aSSNB using 0.375% ropivacaine for analgesia.

Rescue analgesia with serratus anterior plane block improved pain relief after thoracic surgery.

BACKGROUND: Video-assisted thoracic surgery (VATS) is frequently associated with substantial postoperative pain, which may lead to hypopnea. Rescue analgesia using opioids has adverse effects. We aimed to evaluate the effects of rescue analgesia with serratus anterior plane block (SAPB) on moderate-to-severe pain and oxygenation in patients undergoing VATS. METHODS: Eighty patients undergoing VATS and reporting a numeric rating scale (NRS, ranging from 0-10) score of cough pain ≥4 on the first postoperative day were randomized to receive either sufentanil or SAPB for rescue analgesia. The primary outcome was the degree of relief in cough pain 30 min after rescue analgesia. Arterial oxygen pressure (PaO2), opioid consumption after rescue analgesia and the incidence of chronic pain were also assessed. RESULTS: The NRS scores were significantly reduced after rescue analgesia in both groups (Ppaired <0.001). Notably, the degree of relief in cough pain was significantly higher in the SAPB group than that in the sufentanil group (medians [interquartiles]: -3 [-4, -2] vs. -2 [-3, -1], P<0.001). Moreover, patients receiving SAPB exhibited significantly higher PaO2 than those before receiving rescue analgesia (Ppaired=0.007). However, there were no significant differences in the PaO2 before and after receiving rescue analgesia in the sufentanil group. No significant differences in opioid consumption or the incidence of chronic pain were observed between groups. CONCLUSIONS: Rescue analgesia with SAPB on the first postoperative day had a greater effect on pain relief and oxygenation after VATS. However, its long-term effect on chronic pain requires further research.

Effect of oxycodone combined with ultrasound-guided thoracic paravertebral nerve block on postoperative analgesia in patients with lung cancer undergoing thoracoscopic surgery: protocol for a randomised controlled study.

INTRODUCTION: Postoperative pain is a main component influencing the recovery of patients with lung cancer. The combination of patient-controlled intravenous analgesia (PCIA) and paravertebral nerve block for postoperative analgesia in patients undergoing thoracoscopic lobectomy for lung cancer can achieve a satisfactory analgesic effect and promote early rehabilitation of patients. The objective is to investigate the optimal dose of oxycodone for PCIA combined with paravertebral nerve block, to achieve effective multimodal analgesia management in patients undergoing thoracoscopic lung cancer lobectomy. METHODS AND ANALYSIS: This prospective, double-blind, single-centre, parallel-group, superiority study from 7 April 2023 to 31 December 2024 will include 160 participants scheduled for thoracoscopic lobectomy for lung cancer. Participants will be randomly assigned to four groups in a 1:1:1:1 ratio: OCA group (oxycodone: 0.5 mg/kg), OCB group (oxycodone: 1.0 mg/kg), OCC group (oxycodone: 1.5 mg/kg) and one sufentanil group (sufentanil: 2 µg/kg). Flurbiprofen 50 mg and ondansetron 16 mg are added to each group. All the drugs are diluted with 0.9% saline in a 100 mL volume, with a background infusion rate of 2 mL/hour, a bolus dose of 0.5 mL and a lockout interval of 15 min. The primary outcome is pain scores at rest and dynamic at 24 hours after surgery using a Numeric Rating Scale (NRS). Dynamic NRS scores are defined as NRS when coughing. NRS scores will be assessed at 2, 4, 12, 24 and 48 hours postoperatively. The secondary outcomes include the following variables: (1) NRS score at rest and dynamic at 2, 4, 12 and 48 hours postoperatively; (2) total dose of sufentanil or oxycodone consumption in PCIA; (3) the times of patient-controlled analgesia; (4) Ramsay Sedation Score (RSS) at 2, 4, 12, 24 and 48 hours after the surgery; (5) extubation time; (6) serum C-reactive protein and interleukin six levels; (7) incidence of postoperative nausea and vomiting; (8) incidence of itching; (9) incidence of respiratory depression and (10) gastrointestinal recovery (exhaust time). ETHICS AND DISSEMINATION: The First Affiliated Hospital of Shandong First Medical University's Ethics Committee granted consent for this study (approval number: YXLL-KY-2022(116)). To enable widespread use of the data gathered, we plan to publish the trial's findings in an appropriate scientific journal after it is complete. TRIAL REGISTRATION NUMBER: NCT05742256.

A Novel Opioid-Sparing Analgesia Following Thoracoscopic Surgery: A Non-Inferiority Trial.

Purpose: This randomized, non-inferiority study aimed to observe the feasibility of opioid-sparing analgesia based on modified intercostal nerve block (MINB) following thoracoscopic surgery. Patients and Methods: 60 patients scheduled for single-port thoracoscopic lobectomy were randomized to the intervention group or control group. After MINB was performed in both groups at the end of the surgery, the intervention group received patient controlled-intravenous analgesia (PCIA) of dexmedetomidine 0.05 µg/kg/h for 72 h after surgery, and the control group received conventional PCIA of sufentanil 3 µg/kg for 72 h. The primary outcome was a visual analog scale (VAS) on coughing 24 h after surgery. Secondary outcomes included the time to first analgesic request, pressing times of PCIA, time to first flatus, and hospital stay. Results: There was no difference in the cough-VAS at 24 h (median [interquartile range]) between the intervention group [3 (2-4)] and control group [3 (2-4), P = 0.36]. The median difference (95% CI) in the cough-VAS at 24 h was [0 (0 to 1), P = 0.36]. There was no significant difference in the time to first analgesic request, pressing times of PCIA, and hospital stay between groups (P > 0.05). A significant decrease in time to first flatus was observed in the intervention group (P < 0.01). Conclusion: Opioid-sparing analgesia provided safe and analogous postoperative analgesia with a shortened time to first flatus, compared with sufentanil-based analgesia in thoracoscopic surgery. This might be a novel method recommended for thoracoscopic surgery.

Perioperative Administration of Pregabalin and Esketamine to Prevent Chronic Pain After Breast Cancer Surgery: A Randomized Controlled Trial.

Background: Perioperative multimodal analgesia can prevent chronic pain after breast cancer surgery. This study aimed to investigate the efficacy of combined perioperative oral pregabalin and postoperative esketamine in preventing chronic pain after breast cancer surgery. Methods: Ninety patients undergoing elective breast cancer surgery were randomized into the combined pregabalin and esketamine group (EP group) and the general anesthesia alone group (Control group). The EP group received 150 mg of oral pregabalin 1 h before surgery and twice daily for seven days postoperatively, and a patient-controlled analgesia pump after surgery that delivered 100 µg sufentanil + 1.25 mg/kg esketamine + 4 mg tropisetron in 100 mL saline solution intravenously. The Control group received placebo capsules before and after the surgery and routine postoperative analgesia (100 µg sufentanil + 4 mg tropisetron in 100 mL saline solution). The primary outcome was the incidence of chronic pain three and six months after surgery. Secondary outcomes included acute postoperative pain, postoperative opioid consumption, and incidence of adverse events. Results: The incidence of chronic pain in the EP group was significantly lower than in the Control group three (14.3% vs 46.3%, P = 0.005) and six (7.1% vs 31.7%, P = 0.009) months postoperatively. The rest numerical rating scale (NRS) pain scores 1-3 days postoperatively and coughing NRS pain scores 1-7 days postoperatively in the EP group were significantly lower than in the Control group (all P ˂ 0.05). The cumulative sufentanil consumption in the EP group during postoperative 0-12, 12-24, and 24-48, 0-24, and 0-48 hours were significantly lower than in the Control group (all P ˂ 0.05). Conclusion: Combined perioperative oral pregabalin and postoperative esketamine effectively prevented chronic pain after breast cancer surgery, improved acute postoperative pain, and reduced postoperative opioid consumption.

Sufentanil inhibits Pin1 to attenuate renal tubular epithelial cell ischemia-reperfusion injury by activating the PI3K/AKT/FOXO1 pathway.

BACKGROUND: Renal ischemia-reperfusion injury (RIRI) has become a great concern in clinical practice with high morbidity and mortality rates. Sufentanil has protective effects on IRI-induced organ injury. Herein, the effects of sufentanil on RIRI were investigated. METHODS: RIRI cell model was established by hypoxia/reperfusion (H/R) stimulation. The mRNA and protein expressions were assessed using qRT-PCR and western blot. TMCK-1 cell viability and apoptosis were assessed using MTT assay and flow cytometry, respectively. The mitochondrial membrane potential and ROS level were detected by JC-1 mitochondrial membrane potential fluorescent probe and DCFH-DA fluorescent probe, respectively. LDH, SOD, CAT, GSH and MDA levels were determined by the kits. The interaction between FOXO1 and Pin1 promoter was analyzed using dual luciferase reporter gene and ChIP assays. RESULTS: Our results revealed that sufentanil treatment attenuated H/R-induced cell apoptosis, mitochondrial membrane potential (MMP) dysfunction, oxidative stress, inflammation and activated PI3K/AKT/FOXO1 associated proteins, while these effects were reversed by PI3K inhibitor, suggesting that sufentanil attenuated RIRI via activating the PI3K/AKT/FOXO1 signaling pathway. We subsequently found that FOXO1 transcriptionally activated Pin1 in TCMK-1 cells. Pin1 inhibition ameliorated H/R-induced TCMK-1 cell apoptosis, oxidative stress and inflammation. In addition, as expected, the biological effects of sufentanil on H/R-treated TMCK-1 cells were abrogated by Pin1 overexpression. CONCLUSION: Sufentanil reduced Pin1 expression through activation of the PI3K/AKT/FOXO1 signaling to suppress cell apoptosis, oxidative stress and inflammation in renal tubular epithelial cells during RIRI development.

General anesthesia with S-ketamine improves the early recovery and cognitive function in patients undergoing modified radical mastectomy: a prospective randomized controlled trial.

BACKGROUND: Postoperative cognitive dysfunction (POCD) is a common postoperative disorder that is frequently observed after general anesthesia, which seriously threatens the quality of patients' life. Existing studies have demonstrated that S-ketamine plays an important role in improving neuroinflammation. This trial aimed to explore the effects of S-ketamine on quality of recovery and cognitive function in patients following modified radical mastectomy (MRM). METHODS: Ninety patients aged 45 to 70 years with ASA grades of I or II, who underwent MRM, were selected. Patients were randomly assigned to the S-ketamine or control group. In the S-ketamine group, patients were induced with S-ketamine instead of sufentanil and maintained with S-ketamine and remifentanil. In the control group, patients were induced with sufentanil and maintained with remifentanil. The primary outcome was the Mini-Mental State Examination (MMSE) and Quality of Recovery-15 (QoR-15) score. Secondary outcomes including visual analog scale (VAS) score, cumulative propofol and opioids consumption, post anesthesia care unit (PACU) recovery time, occurrence of remedial analgesia, postoperative nausea and vomiting (PONV), other adverse events, as well as patient satisfaction. RESULTS: The global QoR-15 scores at postoperative day 1 (POD1) were significantly higher in the S-ketamine group than in the control group (124 [119.5-128.0] vs. 119 [114.0-123.5], P = 0.002), with a median difference of 5 points (95% confidence interval [CI] [-8 to -2]). Similarly, the global QoR-15 scores at postoperative day 2 (POD2) in the S-ketamine group were significantly higher than in the control group (140.0 [133.0-145.0] vs. 132.0 [126.5-141.5], P = 0.004). In addition, among the five subcomponents of the 15-item scale, S-ketamine group had a higher score in terms of physical comfort, pain, and emotional state both at POD1 and POD2. In terms of MMSE score, S-ketamine could promote the recovery of postoperative cognitive function at POD1, but not at POD2. Furthermore, the consumption of opioids, VAS score, and remedial analgesia in the S-ketamine group decreased significantly. CONCLUSIONS: Collectively, our findings support that general anesthesia with S-ketamine as a potential strategy showed high safety and could not only improve the quality of recovery mainly through improving pain, physical comfort, and emotional state but also promote the recovery of cognitive function on POD1 in patients undergoing MRM. TRIAL REGISTRATION: The study was registered in the Chinese Clinical Trial Registry (registration No:ChiCTR2200057226, Date of registration: 04/03/2022).

Patient-controlled intravenous administration of dexmedetomidine with nalbuphine versus sufentanil for post cesarean delivery analgesia: A retrospective observational study.

This retrospective observational study aims to investigate the patient-controlled intravenous analgesia (PCIA) of dexmedetomidine (DEX) with nalbuphine (NAL) versus sufentanil (SUF) for post-cesarean delivery management. A total of 300 women were evaluated who underwent cesarean section surgery with combined spinal-epidural anesthesia. After surgery, all patients were connected to a patient-controlled analgesia pump. The PCIA protocol was programmed with 0.11 µg/kg/h DEX in combination with 0.03 µg/kg/h SUF in Group I (n = 150) or 0.11 µg/kg/h DEX in combination with 0.03 mg/kg/h NAL in Group II (n = 150). There was no significant difference in incision pain and sedation level between the two groups within 48 h after the surgery assessed by visual analog scale (VAS) and Ramsay sedation scale, respectively. However, at 2, 6, 12, and 24 h after surgery, visceral pain at rest and at mobilization was alleviated in the Group II as compared with the Group I with lower VAS scores. Moreover, fewer adverse reactions were found in the Group II when compared with Group I, including postpartum respiratory depression, nausea/vomiting, urinary retention, and cardiovascular events. Overall, there was an increased patient satisfaction in the Group II as compared with the Group I. Based on the results of this study, it seems that adding NAL to PCIA with DEX, as compared to SUF with DEX, have an effect on reducing the intensity of visceral pain after cesarean section with less adverse reactions and higher patient satisfaction.

Effect of transverse thoracic muscle plane block on postoperative cognitive dysfunction after open cardiac surgery: A randomized clinical trial.

The transversus thoracis muscle plane (TTMP) block provides effective analgesia in cardiac surgery patients. The aim of this study was to assess whether bilateral TTMP blocks can reduce the incidence of postoperative cognitive dysfunction (POCD) in patients undergoing cardiac valve replacement. A group of 103 patients were randomly divided into the TTM group (n = 52) and the PLA (placebo) group (n = 51). The primary endpoint was the incidence of POCD at 1 week after surgery. Secondary outcome measures included a reduction of intraoperative mean arterial pressure (MAP) >20% from baseline, intraoperative and postoperative sufentanil consumption, length of stay in the ICU, incidence of postoperative nausea and vomiting (PONV), time to first faeces, postoperative pain at 24 h after surgery, time to extubation and the length of hospital stay. Interleukin (IL)-6, TNF-α, S-100ß, insulin, glucose and insulin resistance were measured at before induction of anaesthesia, 1, 3and 7 days after surgery. The MoCA scores were significantly lower and the incidence of POCD decreased significantly in TTM group compared with PLA group at 7 days after surgery. Perioperative sufentanil consumption, the incidence of PONV and intraoperative MAP reduction >20% from baseline, length of stay in the ICU, postoperative pain at 24 h after surgery, time to extubation and the length of hospital stay were significantly decreased in the TTM group. Postoperatively, IL-6, TNF-α, S-100ß, HOMA-IR, insulin, glucose levels increased and the TTM group had a lower degree than the PLA group at 1, 3 and 7 days after surgery. In summary, bilateral TTMP blocks could improve postoperative cognitive function in patients undergoing cardiac valve replacement.

S-ketamine promotes postoperative recovery of gastrointestinal function and reduces postoperative pain in gynecological abdominal surgery patients: a randomized controlled trial.

BACKGROUND: This prospective randomized controlled study was designed to evaluate the effect of S-ketamine with sufentanil given intraoperatively and postoperatively on recovery of gastrointestinal (GI) function and postoperative pain in gynecological patients undergoing open abdomen surgery. METHODS: One hundred gynecological patients undergoing open abdomen surgery were randomized into an S-ketamine group (group S) or placebo group (0.9% saline; group C). Anesthesia was maintained with S-ketamine, sevoflurane, and remifentanil-propofol target-controlled infusion in group S and with sevoflurane and remifentanil-propofol target-controlled infusion in group C. All patients were connected to patient-controlled intravenous analgesia (PCIA) pump at the end of the surgery with sufentanil, ketorolac tromethamine, and tropisetron in group C and additional S-ketamine in group S. The primary outcome was the time of first postoperative flatus, and the secondary outcome was postoperative pain score of patients. Postoperative sufentanil consumption within the first postoperative 24 h and adverse events such as nausea and vomiting were recorded. RESULTS: The time of first postoperative flatus in group S was significantly shorter (mean ± SD, 50.3 ± 13.5 h) than that in group C (mean ± SD, 56.5 ± 14.3 h, p = 0.042). The patient's visual analog scale (VAS) pain score 24 h after surgery at rest was significantly lower in group S than in group C (p = 0.032). There were no differences in sufentanil consumption within the first postoperative 24 h, postoperative complications related to PCIA between the two groups. CONCLUSIONS: S-ketamine accelerated postoperative GI recovery and reduced 24 h postoperative pain in patients undergoing open gynecological surgery. TRIAL REGISTRATION: ChiCTR2200055180. Registered on 02/01/2022. It is a secondary analysis of the same trial.

[Effect of Ropivacaine Combined with Dexmedetomidine for Serratus Anterior Plane Block Plus Patient-Controlled Intravenous Analgesia on Postoperative Recovery Quality of Patients Undergoing Thoracoscopic Radical Resection of Lung Cancer].

Objective: To study the postoperative analgesic effect of ropivacaine combined with dexmedetomidine for serratus anterior plane block (SAPB) under ultrasound visualization plus patient-controlled intravenous analgesia (PCIA) in patients undergoing thoracoscopic radical resection of lung cancer. Methods: A total of 129 patients undergoing elective thoracoscopic surgery were enrolled. The patients were randomly assigned to three groups ( n=43 in each group), a normal saline group (control group), a ropivacaine mesylate group (Group R) and a ropivacaine mesylate combined with dexmetomidine hydrochloride group (Group RD). After operation, ultrasound-guided SAPB was performed and patients in the three groups received the injection of 0 mL of 0.9% normal saline, 25 mL of 0.5% ropivacaine, and 25 mL of 0.5% ropivacaine+1 µg/kg dextrometomidine hydrochloride mixture, respectively. In addition, PCIA was used for all the patients. The button on the PCIA pump was pressed when the postoperative pain visual analogue score (VAS)≥4 on coughing, and rescue analgesic of sufentanil was given intravenously at 2.5 µg/bolus. The primary outcome was the VAS scores at rest and on coughing at 10 min (T 1), 6 h (T 2), 12 h (T 3), 24 h (T 4), and 48 h (T 5) after extubation. The secondary outcomes included hemodynamics, the quality of sleep for the first 3 nights after operation, number of times the button on the PCIA pump was pressed, intraoperative and postoperative opioid dosage, time of first postoperative rescue analgesic, duraion of intubation, length of stay at the hospital, adverse reactions, etc. Results: Compared with those of the control group, the VAS scores of the Group R and Group RD were significantly lower at 10 min, 6 h, and 12 h after extubation ( P<0.05). In comparison with Group R, the number of patients requiring rescue analgesia, the time of first postoperative rescue analgesic, the number of times the button on the PCIA pump was pressed, and the total dose of rescue sufentanil were all significantly lower ( P<0.05) in the Group RD. Patients in the Group RD had better sleep quality in the second and third nights after operation and lower incidence of nausea and vomiting ( P<0.05). Conclusion: 0.5% ropivacaine and 1 µg/kg dexmedetomidine SAPB combined with PCIA can significantly reduce postoperative pain and improve postoperative recovery quality in patients undergoing thoracoscopic radical resection of lung cancer.