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Background and objectivesTo investigate the possible effect of postoperatively applied analgesics—epidurally applied levobupivacaine or intravenously applied morphine—on systemic inflammatory response and plasma concentration of interleukin (IL)-6 and to determine whether the intensity of inflammatory response is related to postoperative cognitive dysfunction (POCD).MethodsThis is a randomized, prospective, controlled study in an academic hospital. Patients were 65 years and older scheduled for femoral fracture fixation from July 2016 to September 2017. Inflammatory response was assessed by leukocytes, neutrophils, C reactive protein (CRP) and fibrinogen levels in four blood samples (before anesthesia, 24 hours, 72 hours and 120 hours postoperatively) and IL-6 concentration from three blood samples (before anesthesia, 24 hours and 72 hours postoperatively). Cognitive function was assessed using the Mini-Mental State Examination preoperatively, from the first to the fifth postoperative day and on the day of discharge.ResultsThe study population included 70 patients, 35 in each group. The incidence of POCD was significantly lower in the levobupivacaine group (9%) than in the morphine group (31%) (p=0.03). CRP was significantly lower in the levobupivacaine group 72 hours (p=0.03) and 120 hours (p=0.04) after surgery. IL-6 values were significantly lower in the levobupivacaine group 72 hours after surgery (p=0.02). The only predictor of POCD in all patients was the level of IL-6 72 hours after surgery (p=0.03).ConclusionsThere is a statistically significant association between use of epidural levobupivacaine and a reduction in some inflammatory markers. Postoperative patient-controlled epidural analgesia reduces the incidence of POCD compared with intravenous morphine analgesia in the studied population.Trial registration numberNCT02848599.

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

Background Butorphanol slightly influences the respiratory and circulatory systems, has a better effect on relieving the discomfort caused by mechanical traction, and has a low incidence of postoperative nausea and vomiting (PONV). Combined butorphanol and propofol may suppress postoperative visceral pain, which is avoidable in gastrointestinal endoscopy. Thus, we hypothesized that butorphanol could decrease the incidence of postoperative visceral pain in patients undergoing gastroscopy and colonoscopy. Methods This was a randomized, placebo-controlled, and double-blinded trial. Patients undergoing gastrointestinal endoscopy were randomized to intravenously receive either butorphanol (Group I) or normal saline (Group II). The primary outcome was visceral pain after the procedure 10 min after recovery. The secondary outcomes included the rate of safety outcomes and adverse events. Postoperative visceral pain was defined as a visual analog scale (VAS) score ≥ 1. Results A total of 206 patients were enrolled in the trial. Ultimately, 203 patients were randomly assigned to Group I ( n  = 102) or Group II ( n  = 101). In total, 194 patients were included in the analysis: 95 in Group I and 99 in Group II. The incidence of visceral pain at 10 min after recovery was found to be statistically lower with butorphanol than with the placebo (31.5% vs . 68.5%, respectively; RR: 2.738, 95% CI [1.409–5.319], P  = 0.002), and the notable difference was in pain level or distribution of visceral pain ( P  = 0.006). Conclusions The trial indicated that adding butorphanol to propofol results in a lower incidence of visceral pain after surgery without noticeable fluctuations in circulatory and respiratory functions for gastrointestinal endoscopy patients. Trial registration Clinicaltrials.gov NCT04477733 (PI: Ruquan Han; date of registration: 20/07/2020).

Transversus abdominis plane (TAP) block can provide effective analgesia for abdominal surgery. However, it was questionable whether TAP had additional effect in the context of multimodal analgesia (MMA). Therefore, this study aimed to assess the additional analgesic effect of preoperative TAP block when added to MMA protocol in open gynecological surgery. In this prospective, randomized-controlled trial, 64 patients scheduled for open gynecological surgery were randomized to receive preoperative TAP block (Study group, n = 32) or placebo (Control group, n = 32) in addition to MMA protocol comprising dexamethasone, acetaminophen, flurbiprofen and celecoxib, and rescued morphine analgesia. The primary outcome was rescued morphine within 24 h after surgery. Secondary outcomes included pain scores, adverse effects, quality of recovery measured by 40-item quality of recovery questionnaire score (QoR-40) at 24 h, and quality of life measured with short-form health survey (SF - 36) on postoperative day (POD) 30. The Study group had less rescued morphine than the control group within 24 h [5 (2-9) vs. 8.5 (5-12.8) mg, P = 0.013]. The Study group had lower pain scores at 1 h [3 (2-4) vs. 4 (3-5), P = 0.007], 2 h [3 (2-4) vs. 3.5 (3-5), P = 0.010] and 6 h [3 (2-3) vs. 3 (2.3-4), P = 0.028], lower incidence of nausea at 48 h (25.8% vs. 50%, P = 0.039), and higher satisfaction score [10 (10-10) vs. 10 (8-10), P = 0.041]. The SF-36 bodily pain score on POD 30 was higher in the Study group (59 ± 13 vs. 49 ± 16, P = 0.023). Preoperative TAP block had additional analgesic effect for open gynecological surgery when used as part of multimodal analgesia. Rescued morphine within 24 h was significantly reduced and the SF-36 bodily pain dimension at 30 days after surgery was significantly improved. www.chictr.org.cn (ChiCTR2000040343, on Nov 28 2020).

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).

High-dose remifentanil during surgery paradoxically increases postoperative pain intensity and morphine consumption. Cyclooxygenase inhibitors decrease prostaglandin synthesis, thereby antagonizing N-methyl-d-aspartate receptor activation, and may reduce hyperalgesia. This study was performed to evaluate whether postoperative morphine consumption increased following intraoperative continuous remifentanil infusion and whether this could be prevented by intravenous ibuprofen pretreatment. A randomized controlled study. Single university hospital, study period from September 2014 to March 2015. One hundred and twenty patients undergoing pancreaticoduodenectomy. After induction of anesthesia, patients received remifentanil target-controlled infusion (effect site concentration of 4 ng/mL or 1 ng/mL) with or without intravenous ibuprofen (800 mg). Postoperative cumulative total morphine consumption and pain intensity were assessed. Intraoperative remifentanil use in patients receiving high-dose remifentanil was more than 3-fold higher than that in patients receiving low-dose remifentanil (2666.8 ± 858.4 vs 872.0 ± 233.3 μg, respectively; P< .001). However, cumulative total morphine consumption at postoperative 1, 3, 6, 12, 24, and 48 hours did not differ among the groups. There were no differences among the groups in the self-administered analgesic dose by the patients using a controlled analgesia device, number of self-administration attempts, numerical rating scale for pain, or analgesic side effects. We found no influence on postoperative pain after high-dose remifentanil in patients undergoing pancreaticoduodenectomy. Addition of intravenous ibuprofen did not reduce postoperative morphine consumption or pain intensity. •High-dose remifentanil increases postoperative pain intensity and morphine consumption.•Ibuprofen decreases prostaglandin synthesis and may reduce hyperalgesia.•We found no influence on postoperative pain after high-dose remifentanil infusion.•Intravenous ibuprofen did not reduce morphine consumption or pain intensity.

Objective: Patients with moderate to severe preoperative pain have a high incidence of postoperative pain. The objective of this trial was to evaluate the efficiency of oral premedication with Aceclofenac (immediate release and controlled release) in the management of post-instrumentation pain in root canal treatment, in patients with moderate to severe preoperative pain.Methods: Three-arm parallel, triple blinded randomized controlled trial was planned. Patients with moderate to severe endodontic pain, requiring primary endodontic treatment were enrolled. Aceclofenac 100mg- immediate release (Aceclofenac-IR), Aceclofenac 200mg- controlled release (Aceclofenac-CR), and Ibuprofen 400mg were compared. The tablets were given one hour before the root canal treatment.Postoperatively, patients rated their pain at various time points. The duration of pain relief (primary outcome), the intensity of post-instrumentation pain, and the need for additional medicine were calculated. Statistical analysis was done using Kruskal-Wallis followed by Dunn post-hoc, Chi-square tests, and Binominal logistic regression.Results: Aceclofenac-CR had a statistically significant longest duration of pain relief when compared to Ibuprofen (p=0.037) and Aceclofenac-IR (p=0.026). The intensity of post-instrumentation pain was lowest in Aceclofenac-CR, followed by Aceclofenac-IR and Ibuprofen. Additional medicine was required for only 8% of patients in Aceclofenac-CR group; whereas for 32% in each of Aceclofenac-IR and Ibuprofen groups. The odds of taking additional medicine were reduced to 0.16 in Aceclofenac-CR; increased to 1.05 with age.Conclusion: Aceclofenac-CR had the longest duration of pain relief compared to Aceclofenac-IR and Ibuprofen. (EEJ-2022-03-037)

To evaluate the effects of low-dose butorphanol on hyperalgesia induced by high-dose remifetanil in patients undergoing laparoscopic cholecystectomy. Randomized double-blind clinical trial. Intraoperative. Seventy-five patients scheduled for laparoscopic cholecystectomy were enrolled. Randomly allocated into 3 groups, low dose of remifentanil (LR) group and high dose of remifentanil (HR) group received low (0.1μg kg−1 min−1) or high (0.3μg kg−1 min−1) doses of remifentanil, respectively, and butorphanol combined with remifentanil (BR) group received remifentanil (0.3μg kg−1 min−1) and butorphanol (0.2μg/kg). The visual analog scale scores and cumulative consumption of fentanyl were recorded. Visual analog scale scores were significantly higher in the HR group than in the LR and BR groups (P<.001). The dose of intravenously given fentanyl was significantly higher in the HR group than in the LR and BR groups (P<.001). In addition, the HR group showed a significantly higher cumulative consumption of fentanyl during 5 to 8 hours after the operation (P<.001). A high dose of remifentanil induces postoperative hyperalgesia, which could be prevented by a continuous intravenous administration of a low dose of butorphanol. •Remifentanil enhances postoperative pain through the activation of mu-opioid receptor.•High dose of remifentanil during laparoscopic cholecystectomy induced postoperative hyperalgesia.•Low dose of butorphanol prevented remifentanil-induced postoperative hyperalgesia.

AbstractStudy objectivePostoperative pain management in opioid users remains challenging. The perioperative administration of ketamine might lead to favourable pain outcomes in these patients. Study designA systematic review of randomised controlled trials (RCT) with meta-analysis and assessment of the quality of evidence by GRADE was performed. SettingPerioperative pain treatment. PatientsAdult opioid users undergoing surgery. InterventionsPerioperative administration of ketamine. MeasurementsPrimary outcomes were postoperative acute pain at rest/during movement after 24 h and number of patients with ketamine-related adverse events. Main resultsNine RCTs (802 patients with at least two weeks opioid-intake) were included. There is low-quality evidence that ketamine may slightly reduce postoperative pain during movement after 24 h (mean difference: −0.79; 95% confidence interval (CI): −1.22 to −0.36). Based on a very low-quality of evidence, we are uncertain on any effect of ketamine on pain at rest after 24 h and incidences of adverse events like hallucinations and confusion within 48 h. However, perioperative ketamine reduced cumulative mean opioid consumption by 97.3 mg (95%CI: −164.8 to −29.7) after 24 h and 186.4 mg (95%CI: −347.6 to −25.2) after 48 h. The relative risks (RR) for opioid-related adverse events were significantly different for sedation within 24 h (RR: 0.54; 95%CI 0.37 to 0.78). ConclusionsThere is currently limited evidence for a reduced postoperative pain intensity using perioperative ketamine in preoperative opioid-consuming patients. However, a clinically relevant opioid-sparing effect was evident associated with a reduced risk for postoperative sedation and without increased harm. Therefore, ketamine might be a useful anti-hyperalgesic adjuvant in these patients. Nevertheless, with clinical heterogeneity being considerable, it's too premature to suggest any specific ketamine protocol. Furthermore, many questions (like ideal dosing, treatment duration and more favourable patient-related outcome measures including long-term effects) remain open and need to be addressed in future studies. Protocol registrationProspero CRD42020185497.

Background: Succinylcholine is used for rapid-sequence induction of anesthesia. Fasciculations and myalgia are adverse effects. The pretreatment modalities prevent or minimize its adverse effects. Aims: The present study is designed to evaluate the efficacy of gabapentin on the incidence of fasciculation and succinylcholine-induced myalgia. Settings and Design: The study was conducted at a tertiary care teaching hospital in a randomized, double-blinded, placebo-controlled manner. Materials and Methods: Patients of both genders undergoing laparoscopic cholecystectomy were randomly assigned to two groups. Patients in Group I (Gabapentin group) received 600 mg of gabapentin orally 2 h prior to surgery and patients in Group II (placebo group) received matching placebo. Anesthesia was induced with fentanyl 3 μg/kg, thiopentone 3-5 mg/kg and succinylcholine 1.5 mg/kg. All patients were observed and graded for fasciculations by a blinded observer and patients were intubated. Anesthesia was maintained with oxygen in air, sevoflurane and intermittent vecuronium bromide. After completion of surgery, neuromuscular blockade was reversed. A blinded observer recorded myalgia grade at 24 h. Patients were provided patient-controlled analgesia with fentanyl for postoperative pain relief. Statistical analysis: Demographic data, fasciculation grade, fentanyl consumption, and myalgia grade were compared using student t test and test of proportions. Results: The study included 76 American Society of Anesthesiologists' Grade I or II patients of either gender undergoing laparoscopic cholecystectomy. But only 70 patients completed the study. Results demonstrated that the prophylactic use of gabapentin significantly decreases the incidence and the severity of myalgia (20/35 vs. 11/35) (P<0.05) and decreases fentanyl consumption significantly in the study group (620+164 μg vs. 989+238 μg) (P<0.05) without any effects on the incidence and severity of fasciculations. Conclusions: Prophylactic use of gabapentin 600 mg in laparoscopic cholecystectomy decreases the incidence and severity of myalgia and fentanyl consumption.