Nalbuphine 10mg/1ml solution for injection ampoules

Background and Aims: Post-anaesthesia shivering is distressing and is observed after spinal and general anaesthesia. Nalbuphine, a partial mu-opioid receptor antagonist with kappa-opioid receptor agonist properties, has been successfully used to manage post-anaesthesia shivering. Methods: After registering the review with the International Prospective Register of Systematic Reviews (PROSPERO), we searched PubMed/Medline, Scopus, Ovid, Cochrane Library and clinicaltrials.gov with keywords for randomised controlled trials. The risk of bias-2 (RoB-2) scale was used to assess the quality of evidence. We also used Grading of Recommendations, Assessment, Development and Evaluations (GRADE) guidelines to evaluate the strength of evidence and trial sequential analysis to validate the conclusions. Results: Of the 240 articles, 10 were considered eligible for review (700 patients, 350- nalbuphine, 350- control or placebo). When compared to placebo, the success rate of nalbuphine controlling shivering was significantly better (risk ratio [RR]: 2.37, 95% confidence interval [CI]:1.91, 2.94; P = 0.04, I ² = 94%), but comparable to the control group drugs (opioids, dexmedetomidine, ondansetron, pethidine). Compared to placebo, shivering recurrence was significantly less with nalbuphine than with placebo (RR: 0.47, 95% CI: 0.26, 0.83; P = 0.01, I ² = 61%), but comparable with the control group. The incidence of postoperative nausea/vomiting (PONV) was significantly less with nalbuphine when compared to the control group (RR: 0.67, 95% CI: 0.47, 0.95; P = 0.02, I ² = 37%), but PONV in the nalbuphine group was comparable to placebo (RR: 1.20, 95% CI: 0.68, 2.12; P = 0.54, I ² = 0%). Other outcomes, like the grade of shivering and hypotension, were comparable between the nalbuphine and control groups. Conclusion: Nalbuphine successfully controls post-anaesthesia shivering and reduces the recurrence of shivering.

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Background and Aims Anesthetics such as propofol, esketamine and nalbuphine are used during the upper gastrointestinal endoscopy to achieve and maintain the desired sedation level. The aim of the study was to evaluate the effectiveness and safety of propofol-nalbuphine and propofol-esketamine in children. Methods A multi-centered study was performed at three tertiary class-A hospitals. Children between 3 and 12 years old undergoing diagnostic painless upper gastrointestinal endoscopy were included and randomly divided into esketamine or nalbuphine group to estimate the primary outcome of successful endoscope insertion. The patients were given esketamine 0.5 mg/kg and propofol 2 mg/kg intravenously in esketamine group, with nalbuphine 0.2 mg/kg and propofol 2 mg/kg in the nalbuphine group. The primary outcome was success rate for the first attempt of endoscope insertion in each group. Secondary outcomes included the safety of both anesthesia regimens and gastroenterologist's satisfaction. We used the Face, Leg, Activity, Cry and Consolability (FLACC) scale to evaluate the level of pain before and during the procedure and the Pediatric Anesthesia Emergence Delirium (PAED) scale to assess the level of agitation and delirium after awakening from anesthesia. Results Among 246 patients, 200 were randomly included in the final intention-to-treat analysis, with 100 patients in each group. The success rate for the first attempt of endoscope insertion in the esketamine group was higher than the nalbuphine group (97% vs. 66%; P < 0.01). The heart rate and mean arterial pressure after intraoperative administration in the esketamine group were higher than those in the nalbuphine group, while the delirium incidence during awakening was higher in esketamine group (all P < 0.05). Conclusion The success rate for the first attempt of endoscope insertion of children undergoing upper gastrointestinal endoscopy in the esketamine group was higher than the nalbuphine group, propofol-related hemodynamic changes were reduced accordingly, while the incidence of esketamine-related adverse effects could be high. Clinical Trial Registration Chinese Clinical Trial Registry: ChiCTR2000040500.

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BACKGROUND: Administration of adjuvant drugs epidurally in combination with local anesthetics offers new dimensions in the management of postoperative pain. This study aimed to compare the addition of either nalbuphine or dexmedetomidine to epidural bupivacaine for postoperative analgesia in lower limb orthopedic surgeries under combined spinal-epidural anesthesia. METHODS: This prospective randomized double-blind study included 69 patients scheduled for lower limb orthopedic surgeries. Anesthesia was started with 15 mg hyperbaric bupivacaine 0.5% intrathecally, and then an epidural bolus dose of 12 ml (10 ml 0.25% bupivacaine with 2 ml normal saline in group C, 2 ml (10 mg) nalbuphine in group N or dexmedetomidine 2 ml (100 µg) in group D was administered when sensory regression to T10. Postoperatively, when visual analogue scale (VAS) was ≥ 3, an epidural top-up dose of 8 ml (6 ml 0.25% bupivacaine plus 2 ml normal saline in group C, 2 ml (2 mg) nalbuphine in group N or 20 µg dexmedetomidine (2 ml) in group D was given. The primary outcome was to evaluate the duration of postoperative analgesia and secondary outcomes were any side effects and patient satisfaction. RESULTS: The onset of epidural analgesia was 17.83 ± 2.53 versus 13.39 ± 1.27 versus 12.17 ± 1.27 min in groups C, N and D, respectively (p value < 0.001). The mean duration of analgesia was 241.3 ± 14.24 versus 318.38 ± 22.54 versus 365.87 ± 18.01 min in groups C, N and D, respectively (p value < 0.001). The mean sedation score was less in group C than group N and D (P < 0.001). The patient satisfaction score showed the lowest degree of satisfaction in group C (p value < 0.001). Top-up doses consumed and total analgesic requirements were lower in groups N and D than in group C. There was a statistically significant difference between the studied groups regarding VAS over time (p value < 0.001), intraoperative bradycardia (p value 0.029), and shivering (p value 0.029). CONCLUSION: The addition of either nalbuphine or dexmedetomidine to epidural bupivacaine was effective for postoperative analgesia in terms of onset, duration, and patient satisfaction with the superiority of dexmedetomidine over nalbuphine. TRIAL REGISTRATION: Approval from the research ethics committee of the Faculty of Medicine, Zagazig University was obtained with the reference number (ZU-IRB#:7045-15-8-2021) and it was registered under clinicaltrials.gov (NCT05041270) on registration date 13/09/2021.

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Importance: For patients with idiopathic pulmonary fibrosis (IPF), cough impairs quality of life; effective treatments for IPF-associated cough are needed. Objective: To determine if nalbuphine extended release (ER), a κ opioid receptor agonist and μ-opioid receptor antagonist, decreases cough compared with placebo in patients with IPF-associated cough. Design, Setting, and Participants: In this randomized, double-blind, placebo-controlled phase 2b trial conducted at 52 sites in 10 countries, patients with IPF, chronic cough for at least 8 weeks, and a Cough Severity Numerical Rating Scale (0, no cough; 10, worst possible cough) score of 4 or higher were enrolled from February 2024 to February 2025, with last follow-up in April 2025. Statistical analyses were conducted from May to August 2025. Intervention: Patients were randomized 1:1:1:1 to receive nalbuphine ER at doses of 27 mg, 54 mg, or 108 mg or placebo twice daily for 6 weeks. Main Outcomes and Measures: The primary outcome was the relative change from baseline in 24-hour cough frequency (coughs/h), measured with a digital cough monitor, for nalbuphine ER compared with placebo at week 6. The key secondary outcome was the relative change from baseline in the patient-reported cough frequency (Evaluating Respiratory Symptoms in IPF cough subscale; scores range from 0-4, lower scores indicate lesser cough frequency) at week 6. Results: Of the 223 patients screened, 165 were randomized (42, 43, 40, and 40 to receive nalbuphine ER 27 mg, 54 mg, and 108 mg, and placebo, respectively) and 160 were included in the primary analysis (median age, 71 [range, 51-85] years; 28.5% female). The baseline mean (SD) cough count was 28.3 (27.4) coughs/h. In the nalbuphine ER 27 mg, 54 mg, and 108 mg twice-daily groups, the mean relative decrease in the cough count and the absolute decrease in coughs/h were 47.9% (from 24.6 to 11.9; P = .008), 53.4% (from 28.0 to 14.9; P < .001), and 60.2% (from 31.5 to 11.9; P < .001), respectively, compared with placebo (16.9%; from 29.4 to 28.1 coughs/h). For the key secondary outcome of patient-reported cough frequency at week 6, the relative and absolute changes were -31.4% (from 2.3 to 1.5; P = .14), -40.6% (from 2.6 to 1.4; P = .004), and -40.2% (from 2.4 to 1.4; P < .005) in the 27-mg, 54-mg, and 108-mg groups, respectively, compared with -21.9% (from 2.6 to 1.9) with placebo. Conclusions and Relevance: For patients with IPF-associated chronic cough, all 3 doses of nalbuphine ER reduced objective cough frequency and the 2 higher doses improved patient-reported cough frequency at 6 weeks. Trial Registration: ClinicalTrials.gov Identifier: NCT05964335.

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Background: Erector spinae plane block (ESPB) is an easy and safe method for postoperative analgesia. However its effect lasts only for several hours. This trial was to investigate the effectiveness of different doses of nalbuphine as an adjuvant to ropivacaine in ESPB for patients undergoing percutaneous nephrolithotomy (PCNL). Methods: level for postoperative analgesia. Each subject received 28 mL of 100 mg ropivacaine solution mixed with 2 mL of normal saline (Group R), 2 mL of 10 mg nalbuphine (Group RNL), or 2 mL of 20 mg nalbuphine (Group RNH). Primary outcome was the time to first opioid demand. Secondary outcomes were morphine consumption, VAS scores within 24 h postoperatively, rescue analgesic requirements, and length of hospital stay. Results: The median [interquartile range, IQR] time to first opioid demand was significantly longer in group RNH (8.70 [6.90,14.85] h) than that of group R and group RNL (2.90 [2.00,6.30] h and 5.80 [2.95,7.00] h, respectively). VAS scores (either resting or active) within 24 h postoperatively were comparable between the three groups, with the most significant differences especially at 4, 6, 8 h. Morphine consumption at 24 h postoperatively was significant for R group vs RNH group (median difference, 9; 95% confidence interval [CI], 1.57 to 16.43; p = 0.02). Conclusions: Adding 20mg nalbuphine to ropivacaine in ESPB could significantly improve the effect of analgesia and prolong the duration of nerve blocks for PCNL.

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Remifentanil-induced hyperalgesia (RIH) is a common and complicated issue in patients undergoing laparoscopic cholecystectomy (LC), which significantly reduces patient satisfaction. The present trial was designed to clarify the individual and combined effects of flurbiprofen-axetil and nalbuphine on remifentanil-induced hyperalgesia. This randomized double-blind clinical trial included 120 adult patients who underwent LC at The Second People's Hospital of Wuhu. The individuals were randomized into a flurbiprofen-axetil group (F group), nalbuphine group (N group), flurbiprofen-axetil combined with nalbuphine group (FN group) and saline group (S group). The four groups were given flurbiprofen-axetil (50 mg, iv.), nalbuphine (0.1 mg/kg, iv.), flurbiprofen-axetil (50 mg, iv.) combined with nalbuphine (0.1 mg/kg, iv.) or normal saline respectively prior to skin incision. The primary outcome was the postoperative mechanical pain thresholds at the inner forearm and peri-incisional area. The secondary outcomes were the visual analog scale (VAS) and Ramsay sedation scale at 0.5, 1, 4 and 24 h after surgery, and any other adverse events. The pain threshold of the medial forearm in the FN group did not differ from that in the F and N groups at 24 h after surgery (P=0.310 and P=0.910, respectively). However, the pain threshold around the incision in FN group was significantly lower than that in F and N groups 24 h after surgery (P=0.001). The VAS of the F group, N group and FN group were all significantly lower than that in the S group at 0.5, 1 and 24 h after surgery (P<0.001). No significant differences were observed in the incidence of adverse events between the four groups. Single flurbiprofen-axetil and single nalbuphine effectively prevented RIH 24 h after surgery in LC. The combination of the two analgesic drugs, with different mechanisms of action, was not superior to single therapy. The present study was registered with the Chinese Clinical Trial Registry (registration no. ChiCTR2100045347).

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Background: Different adjuvants have been introduced to enhance the quality of local anesthetics and reduce its adverse events. This study was directed to compare the anesthetic and analgesic properties of intrathecal hyperbaric bupivacaine when three different adjuvant drugs were added. Methodology: One hundred full-term parturients aged 18 to 40 years, scheduled for elective cesarean section, were randomly assigned to 4 groups. Each group received 12.5 mg of 0.5% hyperbaric bupivacaine combined with either 0.5 ml saline (Group-B), 25µg fentanyl (Group-F), 0.8 mg nalbuphine (Group-N) or 2 mg midazolam (Group-M). The outcomes included the postoperative effective analgesia time, the sensorimotor characteristics, postoperative VAS score, pethidine consumption, maternal complications, and neonatal Apgar score. Results: Earlier onset of sensory and motor block was observed in Group F and N than in Group B and M. Duration of postoperative effective analgesia was longer in Groups F, N and M (252.42 ± 46.11, 227.34 ± 36.54 and 243.71 ± 44.95 hours, respectively) than in Group B (172.11 ± 20.99) (P &lt; 0.001). VAS scores decreased in adjuvant groups during the first 12 hours postoperative and required pethidine doses were less. Conclusion: Addition of adjuvant agents to intrathecal bupivacaine improved the quality of subarachnoid block without increasing side-effects. Intrathecal midazolam provided comparable outcomes as the frequently used opioids. Abbreviations: CS: Cesarean section; LA: Local anesthetics; SA: Spinal anesthesia Key words: Intrathecal; Nalbuphine; Midazolam; Fentanyl; Postoperative analgesia; Cesarean section. Citation: Amin SR, Souidan I, Abdelzaam EM. Intrathecal midazolam is a comparable alternative to fentanyl and nalbuphine as adjuvant to bupivacaine in spinal anesthesia for elective cesarean section: a randomized controlled double-blind trial. Anaesth. pain intensive care 2022;27(1):89−96; DOI: 10.35975/apic.v27i1.1923 Received: June 26, 2022; Reviewed: November 28, 2022; Accepted: December 14, 2022

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Background: To investigate the effects of nalbuphine on emergency agitation (EA), which affects up to 80% of the children following otolaryngology procedures, in children undergoing cochlear implantation. Methods: A prospective double-blinded randomized controlled clinical trial was conducted between November 2020 and October 2022. Eligible children, aged 6 months to 3 years old, were randomly assigned to either 0.1 mg/kg, 0.15 mg/kg, 0.2 mg/kg nalbuphine or 0.9% saline groups. EA was defined by the Pediatric Anesthesia Emergence Delirium (PAED) score ≥ 10. Extubation time, post-anesthesia care unit (PACU) length of stay, severe EA (PAED ≥ 15), peak PAED score, the Faces, Legs, Activity, Cry, and Consolability (FLACC) scale, Ramsay sedation score, and adverse events were also recorded. Results: A total of 104 children were enrolled, with 26 children in each group. Nalbuphine significantly reduced the EA occurrence from 73.1% in the saline group to 38.5%, 30.8%, and 26.9% in the 0.1 mg/kg, 0.15 mg/kg, and 0.2 mg/kg nalbuphine groups, respectively ( P < 0.001), without affecting the extubation time and PACU length of stay. More children (34.6%) in the 0.9% saline group experienced severe EA. Higher dose nalbuphine (0.15 mg/kg, 0.2 mg/kg) showed lower peak PAED score, better analgesia and sedation effect compared with 0.1 mg/kg nalbuphine and saline groups. However, 0.2mg/kg nalbuphine caused undesired over-sedation in two (7.7%) children. No other adverse events were reported. Conclusion: Young children undergoing cochlear implantation surgery were at a high risk of EA and postoperative pain, while 0.2 mg/kg nalbuphine might be an ideal candidate for EA and pain prevention when used under close monitoring. Trial Registration: ChiCTR2000040407. Keywords: emergence agitation, nalbuphine, cochlear implantation, postoperative pain

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BACKGROUND: Colonoscopy is essential for diagnosing colon lesions but is often associated with discomfort. Painless colonoscopy techniques are being increasingly used to improve the patient experience."However, in the case of painless colonoscopy, anesthesia is performed outside the operating room, which requires more significant peri-examination of hemodynamic changes and adverse postoperative reactions. This requires a more careful selection of narcotic analgesics, and there needs to be optimal analgesic drug guidance in clinical practice. This study compared the efficacy and safety of nalbuphine and hydromorphone in improving patient comfort and maintaining hemodynamic stability during elective colonoscopy. METHODS: This prospective, randomized, double-blinded controlled trial included 72 adult patients (aged 18-65) who underwent sedation colonoscopy. The 72 patients were randomly divided into two groups using a computer-generated random sequence. Body mass index 18.5-28.0 kg/m2; American Society of Anesthesiologists (ASA) grade I to II. Then, the nalbuphine group was given 0.13 mg/kg nalbuphine, the hydromorphone group was given 0.016 mg/kg hydromorphone, and during the operation, 10-20 mg/time propofol could be appropriately injected according to the patient's examination and cooperation. All patients were continuously monitored for oxygen saturation, heart rate, and noninvasive mean arterial blood pressure. The colonoscopy time and anesthesia time were recorded. Adverse reactions such as hypotension, decreased oxygen saturation, nausea, and vomiting were recorded. Anesthesiologist satisfaction, gastroenterologist (operator), and patient satisfaction were recorded. RESULTS: Both nalbuphine and hydromorphone effectively maintained hemodynamic stability, with no significant differences in vital signs observed between the groups (P > 0.05). However, nalbuphine significantly reduced the incidence of postoperative nausea, vomiting, dizziness, and headache compared to hydromorphone (P < 0.05). The reduced side effects of nalbuphine were marked, suggesting a better postoperative comfort profile. CONCLUSIONS: While nalbuphine and hydromorphone effectively maintain intraoperative vital signs, nalbuphine offers superior postoperative comfort. This makes nalbuphine a preferable analgesic choice in outpatient colonoscopy settings. Further research is warranted to determine the optimal dosages for both drugs and to explore their mechanisms of action in procedural pain management. REGISTER NUMBER: ChiCTR2300077446,November 9, 2023.

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Nalbuphine, a semi-synthetic opioid, has gained attention for its analgesic properties, but its specific impact on hemodynamics in ear, nose, and throat (ENT) surgeries remains a subject of exploration. This comprehensive review aims to systematically analyze existing literature to understand the nuanced hemodynamic effects of nalbuphine during ENT procedures. Nalbuphine demonstrates promise as an analgesic agent in ENT surgeries with generally stable hemodynamic profiles. However, the variability in study designs and outcomes necessitates a cautious interpretation. The review underscores the need for standardized protocols and further research to elucidate patient-specific considerations, ensuring optimal utilization of nalbuphine in enhancing overall perioperative care for ENT patients.

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