Effect of esketamine on postoperative analgesia and postoperative delirium in elderly patients undergoing gastrointestinal surgery.

OBJECTIVE: To investigate the analgesic effect of esketamine combined with low-dose sufentanil in elderly patients after gastrointestinal surgery, and whether the anti-inflammatory effect of esketamine is involved in the mechanism of postoperative delirium. METHOD: We enrolled sixty elderly patients (age ≥ 65 years old, American Society of Anesthesiologists (ASA) grade I-III) who underwent gastrointestinal surgery. Patients were randomly assigned to Group C (control group) who received sufentanil 2 ug/kg, and Group E (experimental group) who received sufentanil 1.5 ug/kg + esketamine 1 mg/kg, with 30 patients in each group. All patients underwent total intravenous anesthesia during the surgery and were connected to a patient-controlled intravenous analgesia (PCIA) pump after surgery. The primary outcome was the evaluation of pain at 4, 24, 48 h after surgery which was evaluated by NRS scores. In secondary outcomes, inflammation was assessed by measuring IL-6 levels using ELISA. The postoperative delirium and the occurrence of adverse reactions were observed on the 1st and 3rd day after surgery. RESULTS: The NRS scores at 4, 24, and 48 h after surgery in the experimental group [(4.53 ± 1.22), (3.46 ± 0.73), (1.37 ± 0.99)] were lower than that in the control group [(5.23 ± 1.16), (4.46 ± 0.77), (2.13 ± 0.78)] (P < 0.05). The concentration of serum IL-6 in the experimental group at 24 and 48 h after operation [(15.96 ± 4.65), (11.8 ± 3.24)] were lower than that in the control group [(23.07 ± 4.86), (15.41 ± 4.01)] (P < 0.05); the incidence of postoperative delirium in the experimental group was less than that in the control group (P < 0.05); there was no significant difference in the incidence of postoperative nausea and vomiting between the two groups (P > 0.05), and neither group had nightmares or delirium. CONCLUSION: Esketamine may enhance postoperative pain management compare with sufentanil, and esketamine has anti-inflammatory effects that reduce the incidence of postoperative delirium. TRIAL REGISTRATION: Full name of the registry: Chinese Clinical Trial Registry. TRIAL REGISTRATION NUMBER: ChiCTR2300072374. Date of registration:2023/06/12.

The median effective concentration of ropivacaine for ultrasound-guided caudal block in children: a dose-finding study.

PURPOSE: To determine the 50% minimum effective concentration (MEC50) and the 95% effective concentration (MEC95) of ropivacaine for ultrasound-guided caudal block during hypospadias repair surgery of pediatric patients. METHODS: Children were enrolled with the American Society of Anesthesiologists (ASA) physical status I-II undergoing elective hypospadias repair surgery. Children were grouped into two age groups: toddlerhood (1-3 years old) and preschool (3-6 years old). We measured The MEC50 using Dixon's up-and-down method. The first children received the caudal block with 1.0 mL/kg of 0.15% ropivacaine. We determined each subsequent patient's concentration based on the previous patient's response and adjusted the concentration in intervals of 0.015%. Meanwhile, the probit regression analysis obtains 95% effective concentration (MEC95). In addition, we recorded the general condition, adverse events, and postoperative pain of each child. RESULTS: 46 children undergoing elective hypospadias repair surgery were included in this study, 22 in the toddlerhood group and 24 in the preschool group. Of the total number of patients, the caudal block was successful in 25 (54%) and failed in 21 (46%). The MEC50 of 1 ml/kg ropivacaine was 0.102% (95% CI 0.099%, 0.138%) in the toddlerhood group and 0.129% (95% CI 0.124%, 0.138%) in the preschool group. The MEC95 of 1 ml/kg ropivacaine was 0.148% (95% CI 0.131%, 0.149%) in the toddlerhood group and 0.162% (95% CI 0.134%, 0.164%) in the preschool group. Our results showed that ropivacaine concentration was statistically different between preschool children and toddlers (P < 0.001). None of the adverse events occurred. CONCLUSIONS: This study showed that children in the preschool group required higher concentrations of ropivacaine than children in the toddler group during ultrasound-guided sacral block combined with non-intubated general anesthesia. At the same time, this method of anesthesia is safe and effective for children undergoing surgery for hypospadias.

Postoperative pain after different doses of remifentanil infusion during anaesthesia: a meta-analysis.

BACKGROUND: This meta-analysis aimed to explore the correlation between the different doses of remifentanil-based anaesthesia and postoperative pain in randomised trials. METHODS: The electronic databases including PubMed, Cochrane, clinical trial registries, and Google Scholar were searched up to November 2022 for randomised controlled trials (RCTs) that assessed the dose dependent efficacy of remifentanil for postoperative pain intensity and hyperalgesia. RESULTS: 31 studies involving 2019 patients were included for analysis. Compared with the high remifentanil dose administration, patients in low doses showed less postoperative pain intensity at 1-2 h (weighted mean differences (WMD): 0.60, 95% CI, 0.05 to 1.15), 3-8 h (WMD: 0.38, 95% CI, 0.00 to 0.75), 24 h (WMD: 0.26, 95% CI, 0.04 to 0.48) and 48 h (WMD: 0.32, 95% CI, 0.09 to 0.55). Remifentanil-free regimen failed to decrease the pain score at 24 h (WMD: 0.10, 95% CI, -0.10 to 0.30) and 48 h (WMD: 0.15, 95% CI, -0.22 to 0.52) in comparison with remifentanil-based anaesthesia. After excluding trials with high heterogeneity, the dose of the remifentanil regimen was closely correlated with the postoperative pain score (P=0.03). In addition, the dose of the remifentanil regimen was not associated with the incidence of postoperative nausea and vomiting (PONV) (P=0.37). CONCLUSIONS: Our meta-analysis reveals that the low dose of remifentanil infusion is recommendable for general anaesthesia maintenance. No evidence suggests that remifentanil-free regimen has superiority in reducing postoperative pain. Moreover, remifentanil doesn't have a dose dependent effect in initiating PONV. TRIAL REGISTRATION: The protocol of present study was registered with PROSPERO (CRD42022378360).

Effects of adding low-dose esketamine to sufentanil and propofol sedation during cervical conization: a single-centre, randomized controlled trial.

BACKGROUND: Cervical conization is a brief but painful procedure that can be performed under sufficient sedation with propofol and opioids. However, this sedation approach comes with a high risk of sedation-related adverse events (SRAEs). Esketamine, an N-methyl-d-aspartate (NMDA) receptor antagonist, causes less cardiorespiratory depression than opioids. The aim of this study was to assess the efficacy and safety of adding a low dose of esketamine to propofol and sufentanil sedation as an opioid-reduced regimen. METHODS: A total of 122 consecutive patients with ASA I-II, body mass index < 30, and STOP-BANG score < 3 who underwent cervical conization were enrolled and randomly divided into Group S and Group ES. Using a closed-loop target-controlled infusion (TCI) pump with a target bispectral index (BIS) value of 60 ± 5, patients in Group S were sedated with 0.2 mcg·kg-1 sufentanil and propofol, while patients in Group ES were sedated with 0.15 mg·kg-1 esketamine, 0.1 mcg·kg-1 sufentanil and propofol. The primary outcome was the incidence and severity of SRAEs, while the secondary outcomes included effectiveness of sedation, awakening time, psychotomimetic side effects, postoperative pain, postoperative nausea and vomiting, and patient and gynaecologist satisfaction. RESULTS: Data from 120 patients were analysed. The incidence of composite SRAEs was significantly higher in Group S than in Group ES (85.0% vs. 56.7%, P < 0.05). Furthermore, the severity of SRAEs was higher in Group S than in Group ES (P < 0.001). There were no significant differences in the effectiveness of sedation, awakening time, psychotomimetic side effects, postoperative pain, postoperative nausea and vomiting, or patient and gynaecologist satisfaction between the two groups. CONCLUSION: Adding low-dose esketamine to propofol and sufentanil sedation reduces the incidence and severity of SRAEs in patients undergoing cervical conization, with equal sedation efficacy, recovery quality, and no additional psychomimetic side effects. TRIAL REGISTRATION: ChiCTR2000040457 , 28/11/2020.

Effect of two different doses of nalbuphine for postoperative analgesia in children with cleft palate: a randomized controlled trial.

BACKGROUND: Cleft palate repair surgery may result in severe pain in the immediate postoperative period. The aim of this study is to compare the effects of different doses of nalbuphine for postoperative analgesia in children with cleft palate. METHODS: From November 2019 to June 2021, 90 children (45 males and 45 females, age 9-20 months old, ASA class I-II) were selected for palatoplasty. They were randomly divided into three groups: the control group (Group C), the N1 group (postoperative analgesia with 0.05 mg/kg/h nalbuphine) and the N2 group (postoperative analgesia with 0.075 mg/kg/h nalbuphine). Each group had 30 cases. Nalbuphine was not continuously infused in Group C but was continuously infused in Groups N1 and N2 at rates of 0.05 mg/kg/h and 0.075 mg/kg/h, respectively, for 24 h for postoperative analgesia. The FLACC analgesia score and Ramsay Sedation score were recorded at 10 min (T1), 30 min (T2), 2 h (T3), 12 h (T4) and 24 h (T5) after the operation. Adverse reactions such as nausea, vomiting and respiratory depression were observed and recorded. RESULTS: Compared with those in Group C, the FLACC scores in the N1 and N2 groups decreased significantly at T1-T5 (p < 0.05); the Ramsay Sedation score in the N1 group was significantly higher at T3 and T4 (p < 0.05), and that in the N2 group was significantly higher at T1-T5 (p < 0.05). Compared with that in the N1 group, the FLACC score in the N2 group was not significantly different, and the Ramsay Sedation score increased significantly at T5 (p < 0.05). CONCLUSION: Using 0.05 mg/kg/h Nalbuphine continuously for 24 h for postoperative analgesia in children with cleft palate has a better effect and fewer adverse reactions. TRIAL REGISTRATION: This study was registered at ChiCTR1900027385 (11/11/2019).

Trajectories of pain and opioid use up to one year after surgery: analysis of a European registry.

BACKGROUND: Long-term opioid use after surgery is a crucial healthcare problem in North America. Data from European hospitals are scarce and differentiation of chronic pain has rarely been considered. METHODS: In a mixed surgical cohort of the PAIN OUT registry, opioid use and chronic pain were evaluated before surgery, and 6 and 12 months after surgery (M6/M12). Subgroups with or without opioid medication and pre-existing chronic pain were analysed. M12-chronic pain was categorised as chronic postsurgical pain (CPSP) meeting the ICD-11 definition, chronic pain related to surgery not meeting the ICD-11 definition, and chronic pain unrelated to surgery. Primary endpoint was the rate of M12 opioid users. Variables associated with M12 opioid use and patient-reported outcomes were evaluated. RESULTS: Of 2326 patients, 5.5% were preoperative opioid users; 4.4% and 3.5% took opioids at M6 and M12 (P<0.001). Chronic pain before operation and at M6/M12 was reported by 41.2%, 41.8%, and 34.7% of patients, respectively (P<0.001). The rate of M12 opioid users was highest in group unrelated (22.3%; related 8.3%, CPSP 1.5%; P<0.001). New opioid users were 1.1% (unrelated 7.1%, related 2.3%, CPSP 0.7%; P<0.001). M12 opioid users reported more pain, pain-related physical and affective interference, and needed more opioids than non-users. The predominant variable associated with M12 opioids was preoperative opioid use (estimated odds ratio [95% confidence interval]: 28.3 [14.1-56.7], P<0.001). CONCLUSIONS: Opioid use was low in patients with CPSP, and more problematic in patients with chronic pain unrelated to surgery. A detailed assessment of chronic pain unrelated or related to surgery or CPSP is necessary. CLINICAL TRIAL REGISTRATION: NCT02083835.

Novel Targets and Drug Delivery System in the Treatment of Postoperative Pain: Recent Studies and Clinical Advancement.

Pain is generated by a small number of peripheral targets. These can be made more sensitive by inflammatory mediators. The number of opioids prescribed to the patients can be reduced dramatically with better pain management. Any therapy that safely and reliably provides extended analgesia and is flexible enough to facilitate a diverse array of release profiles would be useful for improving patient comfort, quality of care, and compliance after surgical procedures. Comparisons are made between new and traditional methods, and the current state of development has been discussed; taking into account the availability of molecular and cellular level data, preclinical and clinical data, and early post-market data. There are a number of benefits associated with the use of nanotechnology in the delivery of analgesics to specific areas of the body. Nanoparticles are able to transport drugs to inaccessible bodily areas because of their small molecular size. This review focuses on targets that act specifically or primarily on sensory neurons, as well as inflammatory mediators that have been shown to have an analgesic effect as a side effect of their anti- inflammatory properties. New, regulated post-operative pain management devices that use existing polymeric systems were presented in this article, along with the areas for potential development. Analgesic treatments, both pharmacological and non-pharmacological, have also been discussed.

Comparison of dexmedetomidine and a dexmedetomidine-esketamine combination for reducing dental anxiety in preschool children undergoing dental treatment under general anesthesia: A randomized controlled trial.

BACKGROUND: Dental anxiety is a widespread complication occurring in pediatric patients during dental visits and may lead to undesirable complications. Esketamine may be effective in anxiety. OBJECTIVE: The objective of this study was to investigate the effect of premedication with a dexmedetomidine-esketamine combination compared with dexmedetomidine alone on dental anxiety in preschool children undergoing dental treatment under general anesthesia. METHODS: This is a prospective, double-blinded, randomized controlled trial. A total of 84 patients were scheduled for elective outpatient dental caries treatment under general anesthesia. Patients were randomly premedicated with intranasal dexmedetomidine (group D) or intranasal dexmedetomidine-esketamine (group DS). The primary outcome was the level of dental anxiety assessed by the Modified Child Dental Anxiety Scale (MCDAS) at 2 h after surgery. Secondary outcomes included level of dental anxiety at 1 day and 7 days after surgery, the incidence of dental anxiety at 2 h, 1 day, and 7 days after surgery, sedation onset time, overall success of sedation, acceptance of mask induction, postoperative pain intensity, incidence of emergence agitation in PACU, adverse reactions, HR, and SpO2 before premedication (baseline) and at 10, 20, and 30 min after the end of study drug delivery. RESULTS: The dental anxiety in group DS was lower than that in group D at 2 h, 1 day, and 7 days postoperatively (P = 0.04, 0.004, and 0.006, respectively). The incidences of dental anxiety in group DS were lower than those in group D at 2 h (53 % vs 76 %, P = 0.03), 1 day (47 % vs 71 %, P = 0.04), and 7 days (44 % vs 71 %, P = 0.02) after surgery. Group DS had a higher success rate of sedation (P = 0.03) but showed a lower MAS score (P = 0.005) and smoother hemodynamics (P < 0.01) after drug administration than group D. Group DS showed a significantly lower incidence rate of emergence agitation (P = 0.03) and postoperative pain intensity (P = 0.006) than that in group D during the anesthesia recovery time. The occurrence of adverse reactions was similar in both groups (P > 0.05). LIMITATIONS: We did not analyze and correct for the learning effect caused by repeated applications of the MCDAS and MCDAS scores on the 1 day after surgery were obtained by telephone follow-up. CONCLUSIONS: Compared to premedication with dexmedetomidine alone, premedication with intranasal dexmedetomidine combined with esketamine could significantly improve dental anxiety in preschool children undergoing dental treatment under general anesthesia.

SIRT2 overexpression decreases remifentanil-stimulated post-surgical hyperalgesia via microglia.

Remifentanil (Remi)-induced hyperalgesia is a serious but common postoperative clinical problem. Sirtuin 2 (SIRT2) is essential in the pathogenetic mechanisms of several neurological disorders. However, whether SIRT2 contributes to the modulation of Remi-induced postsurgical hyperalgesia (POH) is unknown. Here, we investigated the regulatory potential of SIRT2 in Remi-stimulated POH. A rat Remi-stimulated POH model was built by infusing Remi in the surgical incision. Mechanical allodynia and thermal hyperalgesia were separately assessed by paw withdrawal mechanical threshold (PWMT) and paw withdrawal thermal latency (PWTL) measurements. SIRT2 and binding adaptor molecule 1 (Iba1) protein expressions and localization in spinal cord samples were detected by western blot and immunofluorescence. The results revealed SIRT2 downregulation in the spinal cord of rats with Remi-stimulated POH. Intrathecal administration of the overexpression plasmid harboring SIRT2 remarkably relieved mechanical allodynia, along with thermal hyperalgesia in the model animals. Iba1 amounts were increased upon intraoperative incision or Remi infusion, and this effect was more pronounced upon combining both treatments. Furthermore, SIRT2 overexpression suppressed microglia activation in the spinal cord of model animals, and starkly relieved incision- and/or Remi-associated pronociceptive processes as well as spinal microglia activation. SIRT2 elevation relieved Remi-associated POH, likely by suppressing spinal microglia activation. Thus, SIRT2 could be a potent target for treating neuropathic pain.

The effects of a multidisciplinary pathway for perioperative management of patients with hip fracture.

OBJECTIVES: To determine if a multidisciplinary pathway focused on non-opioid pain management, delirium assessment, and resource utilization improved outcomes in geriatric hip fracture patients. The goal was to reduce opioid usage, consultation not congruent with guidelines, and increase use of regional anesthesia to reduce delirium and improve outcomes. METHODS: An observational study was performed on hip fracture patients before and after the intervention. Hospitalists were educated on indications for preoperative cardiac consultation and specialized preoperative cardiac testing according to evidence-based guidelines with the inpatient cardiology service. Additional education on multimodal analgesia, limiting opioids, and peripheral nerve blocks was provided by the acute pain service. Pre-intervention outcomes from 1 July 20171 July 2017 to 31 May 201831 May 2018 (N = 92) were compared to post-intervention outcomes from 1 July 20181 July 2018 to 31 May 201931 May 2019 (N = 98) and included delirium, length of stay, 30-day readmission rate, time from arrival to procedure start time, time to first physical therapy session, and completion of cardiology consult time. We examined adherence, use of nerve blocks, and pre- and post-operative pain scores and opioid use. RESULTS: Delirium was reduced from 50.0% (N = 46/92) to 28.6% (N = 28/98); p = 0.002. Postoperative opioid use (IV morphine milligram equivalents) decreased from an average of 57.2 mg (±67.7) to 42.6 mg (±58.2),P < .0001. There was a significant decrease in mean pre-operative (5.4 ± 4.14 to 5.05 ± 2.8, P < .0001) and post-operative pain scores (4.3 ± 5.2 to 3.2 ± 2.2, P < .0001). There was a significant reduction in time to cardiology consultation from 18 h] to 12 h ; p < .001). CONCLUSIONS: A multidisciplinary collaboration between hospitalists, anesthesiologists, and cardiologists for hip fracture patients was associated with a reduction in pain and delirium and time to cardiologist evaluation. Prospective studies focusing on additional patient-centered outcomes are warranted.

Comparison of the analgesic effects of single-dose 75 mg oral pregabalin versus single-dose 400 mg oral ibuprofen after impacted third mandibular molar surgery: A randomized, double-blind, split-mouth clinical trial.

BACKGROUND: Pain is the most prevalent complication after dentoalveolar surgery. Failure in effective pain control could potentially lead to systemic sequels, such as tachycardia, hypertension, improper nutrition, and central sensitization. Pregabalin is a gamma-aminobutyric acid (GABA) analog with inhibitory and analgesic effects on the central nervous system (CNS). Prescribing gabapentinoids as complementary analgesics reduces the consumption of opioid and non-opioid analgesics, and consequently their side effects. OBJECTIVES: The main purpose of the present study was to compare the analgesic effects of pregabalin (single-dose 75 mg) vs. ibuprofen (single-dose 400 mg) on patients' pain levels after impacted third mandibular molar surgery. MATERIAL AND METHODS: In this randomized, double-blind, split-mouth clinical trial, 24 patients aged 19-34 years volunteered for 2 consecutive (1 month apart) third mandibular molar surgeries (the contralateral teeth). The patients were randomly placed into 2 groups: group G1 (n = 12) was prescribed pregabalin (single-dose 75 mg) after the 1st surgery and ibuprofen (single-dose 400 mg) after the 2nd surgery; and group G2 (n = 12) was prescribed the exact opposite of the G1 arrangement. During the first 24 h post-surgery, the patients recorded the number of complementary analgesics they took (single-dose 400 mg ibuprofen) and their level of pain on a visual analog scale (VAS) every 2 h. RESULTS: The average level of pain at 2 h post-surgery (T1) was significantly lower when pregabalin was prescribed (p < 0.05). Most patients needed complementary analgesics at 4 h post-surgery (T2). However, during the first 24 h post-surgery, the patients required significantly more complementary analgesics when ibuprofen was prescribed. CONCLUSIONS: In comparison with oral ibuprofen (single-dose 400 mg), oral pregabalin (single-dose 75 mg) had a stronger analgesic effect at 2 h after impacted third mandibular molar surgery (p < 0.05). Pregabalin resulted in a significantly lower consumption of complementary analgesics in the first 24 h post-surgery as compared to ibuprofen.

Changes in Surgical Opioid Prescribing and Patient-Reported Outcomes After Implementation of an Insurer Opioid Prescribing Limit.

Importance: Insurers are increasingly limiting the duration of opioid prescriptions for acute pain. Among patients undergoing surgery, it is unclear whether implementation of these limits is associated with changes in opioid prescribing and patient-reported outcomes, such as pain. Objective: To assess changes in surgical opioid prescribing and patient-reported outcomes after implementation of an opioid prescribing limit by a large commercial insurer in Michigan. Design, Setting, and Participants: This was a cross-sectional study with an interrupted time series analysis. Data analyses were conducted from October 1, 2022, to February 28, 2023. The primary data source was the Michigan Surgical Quality Collaborative, a statewide registry containing data on opioid prescribing and patient-reported outcomes from adults undergoing common general surgical procedures. This registry is linked to Michigan's prescription drug monitoring program database, allowing observation of opioid dispensing. The study included 6045 adults who were covered by the commercial insurer and underwent surgery from January 1, 2017, to October 31, 2019. Exposure: Policy limiting opioid prescriptions to a 5-day supply in February 2018. Main Outcomes and Measures: Among all patients, segmented regression models were used to assess for level or slope changes during February 2018 in 3 patient-reported outcomes: pain in the week after surgery (assessed on a scale of 1-4: 1 = none, 2 = minimal, 3 = moderate, and 4 = severe), satisfaction with surgical experience (scale of 0-10, with 10 being the highest satisfaction), and amount of regret regarding undergoing surgery (scale of 1-5, with 1 being the highest level of regret). Among patients with a discharge opioid prescription and a dispensed opioid prescription (prescription filled within 3 days of discharge), additional outcomes included total morphine milligram equivalents in these prescriptions, a standardized measure of opioid volume. Results: Among the 6045 patients included in the study, mean (SD) age was 48.7 (12.6) years and 3595 (59.5%) were female. Limit implementation was not associated with changes in patient-reported satisfaction or regret and was associated with only a slight level decrease in patient-reported pain score (-0.15 [95% CI, -0.26 to -0.03]). Among 4396 patients (72.7%) with a discharge and dispensed opioid prescription, limit implementation was associated with a -22.3 (95% CI, -32.8 to -11.9) and -26.1 (95% CI, -40.9 to -11.3) level decrease in monthly mean total morphine milligram equivalents of discharge and dispensed opioid prescriptions, respectively. These decreases corresponded approximately to 3 to 3.5 pills containing 5 mg of oxycodone. Conclusions: This cross-sectional analysis of data from adults undergoing general surgical procedures found that implementation of an insurer's limit was associated with modest reductions in opioid prescribing but not with worsened patient-reported outcomes. Whether these findings generalize to other procedures warrants further study.

Therapeutic efficacy of intravenous lidocaine infusion compared with thoracic epidural analgesia in major abdominal surgery: a noninferiority randomised clinical trial.

BACKGROUND: Open major abdominal surgery is one of the most risky surgical procedures for acute postoperative pain. Thoracic epidural analgesia (TEA) has been considered the standard analgesic approach. In different reports, lidocaine i.v. has been shown to have an analgesic efficacy comparable with TEA. We compared the analgesic efficacy of i.v. lidocaine with thoracic epidural analgesia using bupivacaine in patients undergoing major abdominal surgery. METHODS: In this noninferiority clinical trial, 210 patients were randomised to thoracic epidural bupivacaine with morphine or i.v. lidocaine. Dynamic pain at 24 h after surgery was measured using a numerical pain rating scale (NPR), and morphine consumption was also measured. A difference in i.v. the lidocaine-epidural bupivacaine NPR of ≤1 for dynamic pain was considered a noninferiority margin. RESULTS: The NPR for dynamic pain in the lidocaine group at 24 h was between 5.7 (1.8) and 5.2 (1.9) in the epidural group, with a difference of 0.53 (95% confidence interval 0.0-1.0). In the first 24 h, the average difference in morphine consumption was 1.8 mg between the i.v. lidocaine and epidural groups (95% confidence interval 1-3 mg). No differences were found in adverse events or complications associated with the procedures. CONCLUSIONS: Intravenous lidocaine is noninferior to thoracic epidural analgesia for acute postoperative pain control in major abdomial surgery at 24 h postoperatively. CLINICAL TRIALS REGISTRATION: NCT04017013.

Outcomes of dexmedetomidine as adjuvant drug in patients undergoing videolaparoscopic cholecystectomy: A randomized and prospective clinical trial.

OBJECTIVE: The repercussions of ischemia-reperfusion and inflammatory response to surgical injury may compromise the return of physiologic processes in video-laparoscopic surgeries. Dexmedetomidine, as an adjuvant drug in general anesthesia, alters the neuroinflammatory reaction, provides better clinical outcomes in the perioperative period, and may reduce the excessive use of chronic medication in patients with a history of addiction. This study evaluated the immunomodulatory potential of dexmedetomidine on perioperative organ function in video-laparoscopic cholecystectomy patients. METHODS: There were two groups: Sevoflurane and Dexmedetomidine A (26 patients) vs. Sevoflurane and Saline 0.9% B (26 patients). Three blood samples were collected three times: 1) before surgery, 2) 4-6h after surgery, and 3) 24h postoperatively. Inflammatory and endocrine mediators were protocolized for analysis. Finally, hemodynamic outcomes, quality upon awakening, pain, postoperative nausea and vomiting, and opioid use were compared between groups. RESULTS: We have demonstrated a reduction of Interleukin 6 six hours after surgery in group A: 34.10 (IQR 13.88-56.15) vs. 65.79 (IQR 23.13-104.97; p = 0.0425) in group B. Systolic blood pressure, diastolic blood pressure, and mean arterial pressure was attenuated in group A in their measurement intervals (p < 0.0001). There was a lower incidence of pain and opioid consumption in the first postoperative hour favoring this group (p < 0.0001). We noticed better quality upon awakening after the intervention when comparing the values of peripheral oxygen saturation and respiratory rate. CONCLUSIONS: Dexmedetomidine provided anti-inflammatory benefits and contributed to postoperative analgesia without the depressive side effects on the respiratory and cardiovascular systems commonly observed with opioids. TRIAL REGISTRATION: Immunomodulatory Effect of Dexmedetomidine as an Adjuvant Drug in Laparoscopic Cholecystectomies, NCT05489900, Registered 5 August 2022-Retrospectively registered, https://clinicaltrials.gov/ct2/show/NCT05489900?term=NCT05489900&draw=2&rank=1.

Discharge of postoperative patients with an opioid prescription is associated with increased persistent opioid use, healthcare expenditures and mortality: a retrospective cohort study.

BACKGROUND: The risk factors for persistent opioid use after surgical discharge and the association between opioid prescription at discharge and postoperative emergency department visits, readmission, and mortality are unclear. METHODS: This population-based retrospective cohort study involved opioid-naive patients who underwent surgical procedures from January 1, 2000 to November 30, 2020. The data source was Hong Kong Hospital Authority Clinical Management System electronic health record. The primary outcome was the incidence of new persistent opioid use. Other study outcomes included 30-day emergency department visits, 30-day readmission, and 30-day all-cause mortality. Multivariable logistic regression models were used to estimate the association between opioid prescription at discharge and persistent opioid use, emergency department visits, readmission, and all-cause mortality. RESULTS: Over a median follow-up of 1 month with 36 104 person-years, 438 128 patients (opioid prescription: 32 932, no opioid prescription: 405 196) who underwent surgical procedures were analysed, of whom 15 112 (3.45%) had persistent opioid use after discharge. Prescribing opioids on discharge was associated with increased risks of developing persistent opioid use (odds ratio [OR]: 2.30, 95% confidence interval [CI]: 2.19-2.40, P<0.001), 30-day emergency department visits (OR: 1.28, 95% CI: 1.23-1.33, P<0.001), 30-day readmission (OR: 1.17, 95% CI: 1.13-1.20, P<0.001), and 30-day all-cause mortality (OR: 1.68, 95% CI: 1.53-1.86, P<0.001). CONCLUSIONS: In this large cohort of patients undergoing surgery, an opioid prescription on discharge was associated with a higher chance of persistent opioid use and increased risks of postoperative emergency department visits, readmission, and mortality. Minimising opioid prescriptions on discharge could improve perioperative patient outcomes.

Intraoperative Methadone in Next-day Discharge Outpatient Surgery: A Randomized, Double-blinded, Dose-finding Pilot Study.

BACKGROUND: Contemporary perioperative practice seeks to use less intraoperative opioid, diminish postoperative pain and opioid use, and enable less postdischarge opioid prescribing. For inpatient surgery, anesthesia with intraoperative methadone, compared with short-duration opioids, results in less pain, less postoperative opioid use, and greater patient satisfaction. This pilot investigation aimed to determine single-dose intraoperative methadone feasibility for next-day discharge outpatient surgery, determine an optimally analgesic and well-tolerated dose, and explore whether methadone would result in less postoperative opioid use compared with conventional short-duration opioids. METHODS: This double-blind, randomized, dose-escalation feasibility and pilot study in next-day discharge surgery compared intraoperative single-dose IV methadone (0.1 then 0.2, 0.25 and 0.3 mg/kg ideal body weight) versus as-needed short-duration opioid (fentanyl, hydromorphone) controls. Perioperative opioid use, pain, and side effects were assessed before discharge. Patients recorded pain, opioid use, and side effects for 30 days postoperatively using take-home diaries. Primary clinical outcome was in-hospital (intraoperative and postoperative) opioid use. Secondary outcomes were 30-day opioid consumption, pain, opioid side effects, and leftover opioid counts. RESULTS: Median (interquartile range) intraoperative methadone doses were 6 (5 to 7), 11 (10 to 12), 14 (13 to 16), and 18 (15 to 19) mg in 0.1, 0.2, 0.25, and 0.3 mg/kg ideal body weight groups, respectively. Anesthesia with single-dose methadone and propofol or volatile anesthetic was effective. Total in-hospital opioid use (IV milligram morphine equivalents [MME]) was 25 (20 to 37), 20 (13 to 30), 27 (18 to 32), and 25 (20 to 36) mg, respectively, in patients receiving 0.1, 0.2, 0.25 and 0.3 mg/kg methadone, compared to 46 (33 to 59) mg in short-duration opioid controls. Opioid-related side effects were not numerically different. Home pain and opioid use were numerically lower in patients receiving methadone. CONCLUSIONS: The most effective and well-tolerated single intraoperative induction dose of methadone for next-day discharge surgery was 0.25 mg/kg ideal body weight (median, 14 mg). Single-dose intraoperative methadone was analgesic and opioid-sparing in next-day discharge outpatient surgery.

The Influence of Intravenous Lidocaine Infusion on Postoperative Outcome and Neutrophil-to-Lymphocyte Ratio in Colorectal Cancer Patients. A Pilot Study.

BACKGROUND AND AIMS: In the last years increasing scientific evidence drew attention on the potential effects of anesthetic drugs on postoperative outcome in cancer patients. Local anesthetics, especially lidocaine, have been intensively studied in relation with postoperative outcome in colorectal cancer patients. Our study objectives were to investigate the effects of perioperative intravenous lidocaine infusion on neutrophil-to-lymphocyte ratio and short-term postoperative outcome. Additionally, we also looked at 1 year outcome after intended radical colorectal cancer surgery. METHODS: 150 patients scheduled for colorectal cancer surgery were randomized to receive sevoflurane anaesthesia with or without 48 hours lidocaine infusion. RESULTS: 73 patients were included in the group A (sevoflurane) and 77 in the group B (sevoflurane with lidocaine). Lidocaine infusion did not modify neutrophil-to-lymphocyte ratio at 24 hours after surgery (p=0.58). Patients receiving intravenous lidocaine had significantly lower morphine consumption (p=0.04), faster mobilization time (p=0.001) and fewer days spent in the hospital (p=0.04). Moreover, at 1 year follow- up, patients in group B had a significant decreased rate of recurrences (p=0.03). There was no significant difference in 1 year survival (p=0.22). CONCLUSIONS: In our study, intravenous lidocaine infusion hastened the postoperative recovery of patients in terms of mobilization, hospital discharge and opioid consumption and reduced 1 year recurrence rate. Further studies on larger groups of patients are needed.

Effect of perioperative high-dose transdermal nicotine patch on pain sensitivity among male abstinent tobacco smokers undergoing abdominal surgery: A randomized controlled pilot study.

BACKGROUND AND AIMS: Previous studies have focused on the role of perioperative nicotine replacement therapy (NRT) in improving the success rate of long-term smoking cessation in tobacco smokers. This study aimed to measure the effectiveness of high-dose NRT in alleviating postoperative pain for male abstinent smokers receiving abdominal surgery. DESIGN: This was a parallel-group, randomized, double-blind and controlled pilot trial. SETTING AND PARTICIPANTS: In total, 101 male smoking-abstinent patients from the Eastern Hepatobiliary Surgery Hospital, Shanghai, China, from 8 October 2018 to 10 December 2021. INTERVENTIONS: Patients started smoking cessation on admission to the hospital ward. Patients received 24-hour transdermal nicotine patches (n = 50) or placebo (n = 51) every day from admission until 48 hours after surgery. MEASUREMENTS: The primary outcomes were pre-surgery pain thresholds and total consumption of analgesics within the first 48 hours after surgery. Secondary outcomes included postoperative pain and sedation scores, nausea, vomiting and fever frequency within the treatment period. FINDINGS: Both pre-surgery electrical and mechanical pain thresholds in the NRT group were higher than those in the placebo group (P = 0.004 and P = 0.020, respectively). The 48-hour postoperative analgesic consumption was significantly lower for smoking-abstinent patients receiving NRT than those receiving placebo (standardized morphine equivalent requirement, median [interquartile range], 1.80 [1.47, 2.32] mg/kg vs 2.22 [1.62, 2.82] mg/kg, P = 0.011). Postoperative pain intensity was significantly lower in the NRT group than that in the placebo group at 1st hour and 24th hour post-surgery (P < 0.001 and P = 0.012, respectively). The incidence of treatment-related adverse events was not significantly different between groups. CONCLUSIONS: Perioperative high-dose nicotine replacement therapy may help to relieve postoperative pain among male smoking-abstinent patients undergoing abdominal surgery.

Prevalence of preoperative opioid usage and its impact on postoperative outcomes: a retrospective cohort study.

PURPOSE: Preoperative opioid treatment increases postoperative adverse events. This study was aimed to analyze preoperative opioid prevalence in countries with low opioid consumption. Additionally, the effect of low opioid usage on postoperative outcomes was also investigated. METHODS: We conducted this single center retrospective cohort analysis in a Japanese university-affiliated hospital to investigate opioid usage and its impact on the duration of postoperative hospitalization and in-hospital mortality. Adult patients who underwent general anesthesia between 2015 and 2020 were included. We extracted the patients' characteristics, surgical information and postoperative outcomes. Subgroup analysis to address opioid dose effect was performed in high and low dose opioid subgroups. RESULTS: Among 20,306 inpatients, 535 (2.63%) patients used opioids preoperatively. Tramadol was the most frequently used opioid. The median morphine equivalent (MME) dose was 15 mg/day. Median duration of hospitalization was 18 and 9 days in the opioid and non-opioid groups, and in-hospital mortality was 2.06% and 0.42%. Multivariable regression analysis demonstrated that preoperative opioid use was associated with a longer duration of hospitalization and in-hospital mortality. Subgroup analysis demonstrated longer durations of hospitalization in both high (> 30 mg/day MME) and low (≤ 30 mg/day MME) dose opioid groups, while higher in-hospital mortality was seen only in the high dose opioid group. CONCLUSIONS: Preoperative opioid usage was one-tenth of the United States average. Despite its low prevalence and small dosage, preoperative opioid usage was associated with poor postoperative outcomes. Dedicated perioperative interventions to prevent opioid-associated adverse events should be developed even in countries with low opioid consumption.

Analgesic efficacy of systemic lidocaine using lean body mass based dosing regime versus placebo in bariatric surgery: a prospective, randomised, double-blind, placebo-controlled, single-centre study.

BACKGROUND: Intravenous lidocaine is used as an adjuvant analgesic agent in perioperative settings. It has been investigated in various patient populations and surgical interventions, but there are limited data on its efficacy, particularly for patients undergoing bariatric surgery. Obese patients are at high risk of postoperative respiratory complications and can be expected to benefit from anaesthetic techniques that minimise opioid administration. METHODS: We studied administration of lidocaine hydrochloride 1% i.v. to general anaesthesia at a dose of 1.5 mg kg-1 (lean body mass×1.28) or placebo in patients undergoing bariatric surgery. Subjects randomly assigned to each group were surveyed for 48 h after surgery for experienced pain (primary outcome), and administered opioids, postoperative nausea and vomiting (PONV), resumption of bowel function, and length of hospital stay (secondary outcomes). RESULTS: We recruited and randomised 140 subjects to either the lidocaine or placebo group; 137 completed the study. Subjects with pain numeric rating scale (NRS) >3 within the first 4 h postoperatively were similar in both groups (proportion of any NRS >3 within first 4 h lidocaine group: 47/68 (69%) vs placebo group: 44/69 (63%), P=0.507; within first h P=0.177, within second h P=0.513, within third h P=0.145, within fourth h P=0.510). There was no difference in maximal pain score, opioid consumption, recovery of bowel function, incidence of PONV, or length of hospital stay. CONCLUSIONS: Lidocaine does not improve postoperative pain scores, analgesia, or any secondary outcomes in patients undergoing bariatric surgery. CLINICAL TRIAL REGISTRATION: NCT03667001.