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      A Dose-Response Relationship Study of Prophylactic Nalbuphine to Reduce Pain During the Awakening Period in Patients Undergoing Laparoscopic Total Hysterectomy: A Randomized, Controlled, Double-Blind Clinical Study


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          Prophylactic intravenous nalbuphine was administered to observe its median effective dose (ED 50) in reducing pain after undergoing laparoscopic total hysterectomy. To investigate the effect of different doses of nalbuphine on postoperative analgesia and adverse reactions in patients.

          Patients and Methods

          The 120 patients undergoing laparoscopic total hysterectomy were divided into 6 groups: group C (control) and group P (5 different doses of nalbuphine) with 20 patients per group. The doses of nalbuphine in group P were in an equally proportional series (groups P1, P2, P3, P4, and P5 received doses of 0.280, 0.200, 0.140, 0.100, and 0.070 mg/kg, respectively), diluted to 20 mL with saline and administered 5 min before the induction of anesthesia. A similar volume (20 mL) of saline was administered to group C 5 min before the induction of anesthesia. The numeric rating scale (NRS) of patients during awakening and after surgery, the number of postoperative salvage analgesia, and the occurrence of postoperative adverse effects were recorded.


          The ED 50 (95% confidence interval (CI)) of nalbuphine in preventing pain during the awakening period in patients calculated using the point-slope method was 0.125 (0.108, 0.145) mg/kg. NRS scores differed among the 6 groups at 30 min and 1 h after extubation ( P < 0.001; P < 0.001). Pairwise comparisons between groups revealed that, at 30 min after extubation, compared with group P1, the NRS scores of groups P4, P5, and C were higher ( P = 0.001, P < 0.001, P < 0.001); compared with group P2, groups P5 and C had higher NRS scores ( P = 0.011, P = 0.001). At 1 h after extubation, the NRS scores of groups P1 and P2 were lower than that of group P4 ( P = 0.046, P = 0.036). Compared with the control, only the group P1 had a lower cough score ( P = 0.009) and there were no differences in the other groups. There were no differences in sedation score at 10 min after extubation, the incidence of adverse events at 24 h postoperatively, or the number of remedial analgesics at 24 h postoperatively ( P > 0.05).


          The ED 50 (95% CI) of nalbuphine as a prophylactic in reducing pain during recovery was 0.125 (0.108, 0.145) mg/kg. Compared with the control, nalbuphine at doses of 0.140, 0.200, and 0.280 mg/kg prevented pain during the awakening period. Among these doses, 0.280 mg/kg was determined to be the best, the occurrence of cough was less during extubation and the postoperative analgesic effect was good. However, it is necessary to pay attention to the occurrence of adverse reactions.

          Most cited references34

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          Opioid and nociceptin receptors regulate cytokine and cytokine receptor expression.

          Opioids were originally discovered because of their ability to induce analgesia, but further investigation has shown that the opioids regulate the function of cells involved in the immune response. We suggest that the regulation of cytokine, chemokine, and cytokine receptor expression is a critical component of the immunomodulatory activity of the opioids. In this paper we review the literature dealing with the regulation of cytokine and cytokine receptor expression by agonists for the three major opioid receptor types (mu, kappa, and delta), and nociceptin, the natural agonist for the orphanin FQ/nociceptin receptor. Although the opioid receptors share a high degree of sequence homology, opposing roles between the kappa opioid receptor (KOR) and the mu opioid receptor (MOR) have become apparent. We suggest that activation of the KOR induces an anti-inflammatory response through the down-regulation of cytokine, chemokine and chemokine receptor expression, while activation of the MOR favors a pro-inflammatory response. Investigation into the opioid receptor-like (ORL1)/nociceptin system also suggests a role for this receptor as a down-regulator of immune function. These effects suggest a broad role for opioids in the modulation of the function of the immune system, and suggest possible targets for the development of new therapeutics for inflammatory and infectious diseases.
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            Perioperative intravenous S-ketamine for acute postoperative pain in adults: A systematic review and meta-analysis

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              Pain after laparoscopic surgery: Focus on shoulder-tip pain after gynecological laparoscopic surgery.

              Laparoscopy, one of minimally invasive procedures, is a commonly used procedure in diagnosis and management of various kinds of clinical problems, including gynecologic organ-related diseases. Compared with conventional exploratory laparotomy, the benefits of laparoscopic surgery include reduction of surgical wound, decreasing in postoperative pain, shortening hospital stay, rapid recovery, and a better cosmetic result. However, there are still up to 80% of patients after laparoscopic surgery complaining of high levels of pain and needing pain relief. Postlaparoscopic pain can be separated into distinct causes, such as surgical trauma- or incision wound-associated inflammatory change, and pneumoperitoneum (carbon dioxide [CO2])-related morphological and biochemical changes of peritoneum and diaphragm. The latter is secondary to irritation, stretching, and foreign body stimulation, leading to phrenic neuropraxia and subsequent shoulder-tip pain (STP). STP is the most typical unpleasant experience of patients after laparoscopic surgery. There are at least 11 strategies available to attempt to decrease postlaparoscopic STP, including (1) the use of an alternative insufflating gas in place of CO2, (2) the use of low-pressure pneumoperitoneum in place of standard-pressure pneumoperitoneum, (3) the use of warmed or warmed and humidified CO2, (4) gasless laparoscopy, (5) subdiaphragmatic intraperitoneal anesthesia, (6) local intraperitoneal anesthesia, (7) actively expelling out of gas, (8) intraperitoneal drainage, (9) fluid instillation, (10) pulmonary recruitment maneuvers, and (11) others and combination. The present article is limited in discussing postlaparoscopic STP. We extensively review published articles to provide a better strategy to reduce postlaparoscopic STP.

                Author and article information

                Drug Des Devel Ther
                Drug Des Devel Ther
                Drug Design, Development and Therapy
                31 March 2022
                : 16
                : 981-990
                [1 ]Department of Anesthesiology, Jinshan Hospital of Fudan University , Shanghai, People’s Republic of China
                [2 ]Department of Anesthesiology, Affiliated Hospital of Xuzhou Medical University , Xuzhou, Jiangsu, People’s Republic of China
                [3 ]Emergency Department, Yichang Central People’s Hospital , Yichang, Hubei, People’s Republic of China
                [4 ]Department of Anesthesiology, Peking University People’s Hospital , Beijing, People’s Republic of China
                [5 ]Department of Anesthesiology, Zhangjiagang First People’s Hospital , Zhangjiagang, Jiangsu, People’s Republic of China
                Author notes
                Correspondence: Dunyi Qi, Department of Anesthesiology, Affiliated Hospital of Xuzhou Medical University , Xuzhou, Jiangsu, People’s Republic of China, Email qdy6808@163.com

                These authors contributed equally to this work

                Author information
                © 2022 Wang et al.

                This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License ( http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms ( https://www.dovepress.com/terms.php).

                : 31 December 2021
                : 19 March 2022
                Page count
                Figures: 1, Tables: 12, References: 34, Pages: 10
                Original Research

                Pharmacology & Pharmaceutical medicine
                gynecology,laparoscopy,preventive analgesia,nalbuphine,ed50
                Pharmacology & Pharmaceutical medicine
                gynecology, laparoscopy, preventive analgesia, nalbuphine, ed50


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