Nalbuphine in Pediatric Emergence Agitation Following Cochlear Implantation: A Randomized Trial.

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.

Amphiphilic NLC-Gel formulation loaded with Sebacoyl dinalbuphine ester and Nalbuphine for localized postoperative pain management.

Opioids are powerful analgesics; however, their significant systemic adverse effects and the need for frequent administration restrict their use. Nalbuphine (NA) is a κ-agonist narcotic with limited adverse effects, but needs to be frequently administrated due to its short elimination half-life. Whereas sebacoyl dinalbuphine ester (SDE) is a NA prodrug, which can effectively prolong the analgesic effect, but lacks immediate pain relief. Therefore, in this study, a rapid and sustained local delivery formulation to introduce NA and SDE directly into surgical sites was developed. An amphiphilic nanostructured lipid carrier (NLC) poloxamer 407 (P407) gel (NLC-Gel) was developed to permit concurrent delivery of hydrophobic SDE from the NLC core and hydrophilic NA from P407, offering a dual rapid and prolonged analgesic effect. Benefiting from the thermal-sensitive characteristic of P407, the formulation can be injected in liquid phase and instantly transit into gel at wound site. NLC-Gel properties, including particle size, drug release, rheology, and stability, were assessed. In vivo evaluation using a rat spinal surgery model highlighted the effect of the formulation through pain behavior test and hematology analysis. NLC-Gels demonstrated an analgesic effect comparable with that of commercial intramuscular injected SDE formulation (IM SDE), with only 15 % of the drug dosage. The inclusion of supplemental NA in the exterior gel (PA12-Gel + NA) provided rapid drug onset owing to swift NA dispersion, addressing acute pain within hours along with prolonged analgesic effects. Our findings suggest that this amphiphilic formulation significantly enhanced postoperative pain management in terms of safety and efficacy.

Effectiveness and safety of prehospital analgesia with nalbuphine and paracetamol versus morphine by paramedics - an observational study.

BACKGROUND: Despite the development of various analgesic concepts, prehospital oligoanalgesia remains very common. The present work examines prehospital analgesia by paramedics using morphine vs. nalbuphine + paracetamol. METHODS: Patients with out-of-hospital-analgesia performed by paramedics from the emergency medical services of the districts of Fulda (morphine) and Gütersloh (nalbuphine + paracetamol) were evaluated with regards to pain intensity at the beginning and the end of prehospital treatment using the Numeric-Rating-Scale for pain (NRS), sex, age, and complications. The primary endpoint was achievement of adequate analgesia, defined as NRS < 4 at hospital handover, depending on the analgesics administered (nalbuphine + paracetamol vs. morphine). Pain intensity before and after receiving analgesia using the NRS, sex, age and complications were also monitored. RESULTS: A total of 1,808 patients who received out-of-hospital-analgesia were evaluated (nalbuphine + paracetamol: 1,635 (90.4%), NRS-initial: 8.0 ± 1.4, NRS-at-handover: 3.7 ± 2.0; morphine: 173(9.6%), NRS-initial: 8.5 ± 1.1, NRS-at-handover: 5.1 ± 2.0). Factors influencing the difference in NRS were: initial pain intensity on the NRS (regression coefficient (RK): 0.7276, 95%CI: 0.6602-0.7950, p < 0.001), therapy with morphine vs. nalbuphine + paracetamol (RK: -1.2594, 95%CI: -1.5770 - -0.9418, p < 0.001) and traumatic vs. non-traumatic causes of pain (RK: -0.2952, 95%CI: -0.4879 - -0.1024, p = 0.002). Therapy with morphine (n = 34 (19.6%)) compared to nalbuphine + paracetamol (n = 796 (48.7%)) (odds ratio (OR): 0.274, 95%CI: 0.185-0.405, p < 0.001) and the initial NRS score (OR:0.827, 95%CI: 0.771-0.887, p < 0.001) reduced the odds of having an NRS < 4 at hospital handover. Complications occurred with morphine in n = 10 (5.8%) and with nalbuphine + paracetamol in n = 35 (2.1%) cases. Risk factors for complications were analgesia with morphine (OR: 2.690, 95%CI: 1.287-5.621, p = 0.008), female sex (OR: 2.024, 95%CI: 1.040-3.937, p = 0.0379), as well as age (OR: 1.018, 95%CI: 1.003-1.034, p = 0.02). CONCLUSIONS: Compared to morphine, prehospital analgesia with nalbuphine + paracetamol yields favourable effects in terms of analgesic effectiveness and a lower rate of complications and should therefore be considered in future recommendations for prehospital analgesia.

Ultrasound-guided pericapsular nerve block compared with IV opioids in hip injuries: A randomised controlled trial.

STUDY OBJECTIVES: The study aimed to compare the analgesic effect of USG-guided PENG (Peri capsular nerve group) block with Intravenous Nalbuphine hydrochloride (IVN) in patients with hip fracture coming to the emergency department (ED). The purpose was also to monitor the adverse effects and rescue analgesic requirements in both treatment modalities. METHODS: The study was an open-label randomised controlled trial (RCT) comparing PENG block versus IVN in treating patients with femoral head and neck fractures, as well as pubic rami fracture of the hip (HF). The participants in the PENG group received a USG-guided PENG block by injection of 25 ml of 0.25% bupivacaine, whereas the IVN group received 0.15 mg/kg of nalbuphine. An emergency physician with expertise in ultrasound-guided nerve blocks performed the PENG blocks. The primary outcome was to measure the improvement of the NRS (Numerical rating scale) score at 30 min in both static position (Patient-chosen position for the best comfort) and dynamic position (15-degree passive affected lower limb elevation). Secondary outcomes were to measure static and dynamic NRS pain scores at 2 h, 4 h, and 6 h after intervention in both groups. The requirement for rescue analgesia, adverse events and any block-related complications were also recorded. RESULTS: A total of 60 patients with HF were included in the final analysis. The static and dynamic NRS score was significantly lower in the PENG group compared to the IVN group at 30 min, 2 h, 4 h, and 6 h post-intervention. In the PENG group, the static NRS score was improved by 5.73 ± 1.17, while In the IVN group, the static NRS score was just improved by 2.13 ± 0.97 at 30 min. In the same duration, the Dynamic NRS score in the PENG group was improved by 6.13 ± 1.38, while In the IVN group, it improved just by 2.43 ± 1.28. Rescue analgesia was required in 50.0% of patients in the IVN group but none in the PENG group. Further, no block-related complications or adverse events were observed in the patients of the PENG group. CONCLUSION: The study provides evidence that the ultrasound-guided PENG block has a better analgesic effect and has fewer adverse events than IV opioids in patients with HF.

Regional analgesia using ultrasound-guided intermediate cervical plexus block versus cervical erector spinae block for anterior cervical spine surgery: a randomized trial.

BACKGROUND: Regional analgesia techniques are crucial for pain management after cervical spine surgeries. Anesthesiologists strive to select the most effective and least hazardous regional analgesia technique for the cervical region. Our hypothesis is that an intermediate cervical plexus (IC) block can provide adequate postoperative analgesia compared to a cervical erector spinae (ES) block in patients undergoing anterior cervical spine surgery. METHODS: In this double-blind prospective trial, 58 patients were randomly assigned into two equal groups prior to the administration of general anesthesia. Patients in the IC group (n = 29) underwent ultrasound-guided bilateral intermediate cervical plexus block with 15 ml of bupivacaine 0.25% administered to each side. The ES group (n = 29) underwent ultrasound-guided bilateral cervical erector spinae plane blocks with 15 ml of 0.25% bupivacaine administered to each side at the C6 level. The primary outcome was to record the time to the first call for rescue analgesia (nalbuphine), and the secondary outcomes were to measure the performance time, the onset of the sensory block, the intraoperative fentanyl consumption, postoperative pain intensity using VAS, the postoperative total nalbuphine consumption, and postoperative complications such as nausea, vomiting, hypotension, and bradycardia. RESULTS: The performance and onset of sensory block times were significantly shorter in the IC group compared to the ES group. The time to first call for nalbuphine was significantly shorter in the IC group (7.31 ± 1.34 h) compared to the ES group (11.10 ± 1.82 h). The mean postoperative VAS scores were comparable between the two groups at the measured time points, except at 8 h, where it was significantly higher in the IC group, and at 12 h, where it was significantly higher in the ES group. The total nalbuphine consumption was significantly higher in the IC group (33.1 ± 10.13 mg) compared to the ES group (22.76 ± 8.62 mg). CONCLUSIONS: For patients undergoing anterior cervical spine surgery, the intermediate cervical plexus block does not provide better postoperative regional analgesia compared to the cervical erector spinae block. Performance time and onset time were shorter in the IC group, whereas nalbuphine consumption was lower in the ES group. TRIAL REGISTRATION: The trial was registered at clinicaltrials.gov. (NCT05577559, and the date of registration: 13-10-2022).

A randomized, double-blind study to compare the efficacy and safety of nalbuphine nasal spray and injectable solution in patients after orthopaedic interventions and traumatological procedures.

AIMS: Our previous 3-period crossover study in healthy volunteers comparing the pharmacokinetics of nalbuphine nasal spray Apain with parenteral nalbuphine solution demonstrated high bioavailability of the nasal spray and close similarity of pharmacokinetic profiles after intranasal and intramuscular administration, especially within 30 min postdose. The aim of the present study was a noninferiority assessment of nalbuphine nasal spray vs. intramuscular injection for pain relief in postoperative patients. METHODS: Ninety orthopaedic and traumatology patients were enrolled in this double-blind, randomized study of the effectiveness and tolerance of a single 10.5 mg dose of nalbuphine nasal spray vs. 10 mg intramuscular injection. The summed pain intensity difference (SPID0-6) calculated using visual analogue scale scores was the primary study endpoint. RESULTS: Of 90 subjects enrolled, the per-protocol efficacy population comprised 79 patients; 6 patients in the reference group and 5 patients in the test group were excluded due to remedication. The mean values of study endpoints with 95% confidence interval were as follows in reference and test groups, respectively: SPID0-6 = 228.08 (205.73-250.43) vs. 248.73 9 (225.83-271.63), time to pain relief onset = 0.28 h (0.25-0.31) vs. 0.27 h (0.25-0.29), duration of analgesia = 5.55 h (5.17-5.93) vs. 5.51 h (5.10-5.92), area under the curve = 119.30 (91.17-147.43) vs. 99.81 (74.52-107.10). No statistically significant differences were revealed. CONCLUSION: Nalbuphine nasal spray Apain has been proven to be a safe, noninvasive alternative to intramuscular nalbuphine to relieve severe postoperative pain. Designed for self-administration and dose-adjusting, the noncontrolled opioid analgesic nalbuphine spray can be used for patient-controlled analgesia in out-of-hospital, field and home settings.

Breast Milk Excretion of Dinalbuphine Sebacate Injection Administered After Cesarean Section.

Ensuring the safety of analgesics during lactation is crucial for women of childbearing potential. Available data regarding the transfer of nalbuphine for postoperative acute pain via breast milk are limited to the postmarketing experience. This lactation study aimed to assess nalbuphine and dinalbuphine sebacate concentrations in breast milk from lactating women with postoperative pain treated with dinalbuphine sebacate extended-release injection (150 mg dinalbuphine sebacate/2 mL Naldebain). Breast milk was collected throughout the 5-day posthospitalization interval from 20 mothers injected with one dose of extended-release dinalbuphine sebacate intramuscularly. Maternal safety was assessed during the study period. Nalbuphine was detectable in 71% of milk samples collected from all mothers, whereas dinalbuphine sebacate was undetectable or below the quantitation limit (0.1 ng/mL). The mean nalbuphine concentration in milk was approximately 10.55 ng/mL, with the peak concentration reaching up to 12.7 ng/mL. The mean relative infant dose was 0.39% (coefficient of variation, 65%). The mean pain intensity at rest was reduced to mild pain from Day 2 morning to discharge. Overall, the maternal safety profile was tolerable. The breast milk of women who receive one dose of dinalbuphine sebacate injection postpartum contains low nalbuphine concentration. In addition, dinalbuphine sebacate injection potentially reduces maternal pain intensity during the first postpartum week and offers low toxicity risk among breastfed infants.

Pharmacokinetics and tolerability of intranasal or intravenous administration of nalbuphine in infants.

OBJECTIVES: Intranasal nalbuphine could be a safe, efficacious and non-invasive alternative to parenteral pain medication in infants. We aimed to assess pharmacokinetics (PK) and tolerability of intranasal and intravenous nalbuphine administration in infants. METHODS: Prospective open-label study including infants 1-3 months of age admitted to the emergency department, receiving nalbuphine for procedural pain management. Patients were alternately allocated to a single nalbuphine dose of 0.05 mg/kg intravenously or 0.1 mg/kg intranasally. Nalbuphine PK samples were collected 15, 30 and 120-180 min after dosing. Area under the concentration time curve (AUC0-Tlast) was calculated by non-compartmental analysis (NCA) and compared by Wilcoxon test. Neonatal Infant Pain Score was assessed during nalbuphine administration and the following interventions: venous access, urinary catheterisation, lumbar puncture. RESULTS: Out of 52 study subjects receiving nalbuphine, 31 were eligible for NCA (11 intravenous, 20 intranasal). Median AUC0-Tlast after 0.05 mg/kg intravenously was 8.7 (IQR: 8.0-18.6) µg×L/hour vs 7.6 (5.4-10.4) µg×L/hour after intranasal administration of 0.1 mg/kg (p=0.091). Maximum serum concentration (Cmax) was observed 30 min after intranasal administration (3.5-5.6 µg/L). During intravenous and intranasal nalbuphine administration, mild to no pain was recorded in 71% and 67% of study subjects, respectively. CONCLUSION: This is the first study investigating intranasal administration of nalbuphine in infants suggesting an intranasal bioavailability close to 50%. Non-invasive intranasal application was well tolerated. Additional studies are warranted to optimise dosing and timing of interventions as Cmax is delayed by half an hour after intranasal administration. TRIAL REGISTRATION NUMBER: NCT03059511.

Comparison of Preemptive Effect of Intravenous Ketorolac Versus Nalbuphine on Postoperative Shivering and Pain in Patients Undergoing Surgery Under Spinal Anesthesia: A Prospective, Randomized, Double-Blind Study.

BACKGROUND: Postoperative pain and postanesthesia shivering are the two common problems in patients undergoing surgery under spinal anesthesia (SA). The present study aimed to compare the preemptive prescription of the single dose of intravenous (IV) ketorolac versus nalbuphine on postoperative shivering and pain in patients undergoing surgery under SA. METHODS: Present study was a prospective, randomized double-blind study, conducted on patients of either gender, with American Society of Anesthesiologists physical status class I or II, aged 21-60 years, posted for elective lower abdominal surgeries under SA. Patients were randomized by computer-generated random numbers into two groups of 50 patients each: group N (received 0.2 mg/kg nalbuphine IV) and group K (received 0.5 mg/kg ketorolac IV). RESULTS: The incidence of postoperative shivering was 22 % and 36 % in groups N and K respectively and the difference was statistically significant. The first request for analgesia (minutes) was later in group N (295.17 ± 54.62) than in group K (223.80 ± 15.34) and the difference was statistically significant. Increased total analgesic consumption was noted more in group K (131.34 ± 43.27) than in group N (79.23 ± 21.34), and the difference was statistically significant (P < 0.0001). The incidence of side effects was comparable among both groups. CONCLUSION: Preemptive nalbuphine had less incidence of postoperative shivering, delayed first request for analgesia, and less total analgesic consumption than ketorolac in patients undergoing surgery under SA.

Effect of Subcostal Anterior Quadratus Lumborum Block vs. Oblique Subcostal Transversus Abdominis Plane Block after Laparoscopic Radical Gastrectomy.

OBJECTIVE: To evaluate the analgesic effect of ultrasound-guided subcostal anterior quadratus lumborum block (QLB) for laparoscopic radical gastrectomy surgery. METHODS: Patients (aged 20-65 years, ASA I - II, and weighing 40-75 kg) scheduled for elective laparoscopic radical gastrectomy were enrolled in the current study. Sixty patients were randomly assigned to two groups by computer-generated randomization codes: an ultrasound-guided oblique subcostal transversus abdominis plane block (TAPB) group (group T, n=30) or an ultrasound-guided subcostal anterior QLB group (group Q, n=30). In both groups, bilateral ultrasound-guided oblique subcostal TAPB and subcostal anterior QLB were performed before general anesthesia with 0.25% ropivacaine 0.5 mL/kg. For postoperative management, all patients received patient-controlled intravenous analgesia (PCIA) with nalbuphine and sufentanil after surgery, maintaining visual analogue scale (VAS) scores ≤4 within 48 h. The intraoperative consumption of remifentanil, the requirement for sufentanil as a rescue analgesic, and the VAS scores at rest and coughing were recorded at 1, 6, 12, 24 and 48 h after surgery. The recovery (extubation time after surgery, first ambulation time, first flatus time and length of postoperative hospital stay) and the adverse events (nausea and vomiting, skin pruritus, respiratory depression and nerve-block related complications) were observed and recorded. The primary outcome was the perioperative consumption of opioids. RESULTS: Compared with group T, the intraoperative consumption of remifentanil, requirement for sufentanil and the frequency of PCIA were reduced in group Q. Meanwhile, VAS scores at all points of observation were significantly lower in group Q than in group T. Patients in group Q were also associated with shorter time to first out-of-bed activity and flatus, and shorter length of postoperative hospital stay than group T (P<0.05). There were no skin pruritus, respiratory depression or nerve-block related complications in both groups. CONCLUSION: Compared with ultrasound-guided oblique subcostal TAPB, ultrasound-guided subcostal anterior QLB provided greater opioid-sparing effect, lower visual analogue scores, and shorter postoperative hospital stay for laparoscopic radical gastrectomy.

Different Doses of Nalbuphine Combined with Dexmedetomidine in Laparoscopic Oophorocystectomy.

BACKGROUND The goal of this study was to investigate different doses of nalbuphine combined with dexmedetomidine in the postoperative treatment of laparoscopic oophorocystectomy. MATERIAL AND METHODS This prospective single-blinded randomized controlled study included 219 patients with benign ovarian cysts who received laparoscopic oophorocystectomy from March 2017 to October 2019. Patients were randomized into 4 groups: low (0.5 mg/kg), middle (1.0 mg/kg), and high (1.5 mg/kg) doses of nalbuphine combined with dexmedetomidine (4 µg/kg) (LND, MND, and HND groups, respectively) and a control group with sufentanil (2.5 µg/kg), with different patient-controlled intravenous analgesia pump (PCIA) strategies. Rest and active visual analog scale (VAS) scores measured postoperative pain, and Ramsay scores were used to measure sedation. RESULTS The HND group showed the lowest rest and cough VAS scores at 2 h, 8 h, 12 h, and 24 h after surgery, the lowest PCIA pressing time within 48 h after surgery, and the highest Ramsay scores at 2 h, 8 h, 24 h and 48 h after surgery. Rest and cough VAS scores decreased with higher nalbuphine doses in a dose-dependent manner. One day after surgery, IL-1ß and IL-6 levels increased in all groups, with the lowest levels of IL-1ß and IL-6 in the HND group. Hospitalization time was significantly shorter in the HND group compared with the LND and MND groups. There were no significant differences in complications among groups. CONCLUSIONS Combined nalbuphine and dexmedetomidine improved postoperative pain and sedative conditions, reduced inflammation in a nalbuphine dose-dependent manner, and might facilitate patient recovery.

Pharmacokinetic comparison of nalbuphine with single injection and patient-controlled analgesia mimic method in healthy Chinese volunteers.

WHAT IS KNOWN AND OBJECTIVE: Nalbuphine is a mu (µ) receptor partial antagonist/kappa (κ) receptor agonist analgesic and can be administered as a single injection or using patient-controlled analgesia (PCA) in the clinical setting. However, differences in the pharmacokinetics of the two administration methods are unclear. Here, a clinical trial was performed to compare the pharmacokinetic characteristics and superiority of nalbuphine with a single-injection or PCA-mimic method to provide a reference for the selection of an appropriate administration method. METHODS: Twenty healthy individuals were divided into two groups and injected with 10 mg nalbuphine intravenously using a single-injection or a PCA-mimic method (2 mg once for five times with a 30-min interval). Blood samples were collected, and safety was investigated. The liquid chromatography-tandem mass spectrometry was adopted to determine the concentration of nalbuphine in plasma. RESULTS AND DISCUSSION: The maximum concentration (Cmax ) and area under concentration-time curve (AUC0-t ) values of nalbuphine in the single-injection and PCA groups were as follows: Cmax , 81.3 ± 24.7 and 39.8 ± 6.4 ng/ml, respectively; moreover, AUC0-t , 110.3 ± 19.5 and 128.3 ± 23.0 h ng/ml, respectively. The effective analgesic concentration durations (EACDs) for the two administration methods were 1.39 ± 0.64 and 1.96 ± 0.91 h, respectively. Nalbuphine was well tolerated, and improvements were observed in the PCA group. WHAT IS NEW AND CONCLUSION: Compared with those in the single-injection group, the AUC0-t and EACDs in the PCA group were similar, whereas Cmax was decreased significantly. Therefore, the PCA method was more suitable for the clinical application of nalbuphine injection owing to the superiority of lower concentration fluctuation and the improved safety profile.

Nasal nalbuphine analgesia in prehospital trauma managed by first-responder personnel on ski slopes in Switzerland: an observational cohort study.

BACKGROUND: Pain is one of the major symptoms complained about by patients in the prehospital setting, especially in the case of trauma. When there is mountainous topography, as in Switzerland, there may be a time delay between injury and arrival of professional rescuers, in particular on ski slopes. Administration of a safe opioid by first responders may improve overall treatment. We therefore assessed administration of nasal nalbuphine as an analgesic treatment for trauma patients in Switzerland. METHODS: This observational cohort study examined 267 patients who were treated with nasal nalbuphine by first responders in six ski resorts in Switzerland. All first responders were instructed to begin treatment by assessing the feasibility of using nalbuphine to treat pain in the patient. A treatment algorithm was developed and distributed to assure that nalbuphine was only administered following a strict protocol. Data regarding pain scores and pain reduction after administration of nalbuphine were collected on-site. Refills were handed out to the first responders with the return of each completed questionnaire. RESULTS: Nalbuphine provided effective pain relief, with the median level of pain on the numeric rating scale for pain reduced by 3 units on average, from 8 points (p < 0.001). The multivariate regression model showed that pain reduction was more pronounced in patients with higher initial pain levels. Nalbuphine was more effective in adolsecents than in patients aged 20 to 60 years (p = 0.006). No major side effects were observed. CONCLUSION: Nasal administration of nalbuphine by first responders is a presumably safe and effective noninvasive pain management strategy for acutely injured patients in the prehospital setting. This may be an alternative, especially in the case of severe pain and prolonged time between arrival of the first responders and arrival of EMS/HEMS personnel on scene.

Pain management after ambulatory surgery: a prospective, multicenter, randomized, double-blinded parallel controlled trial comparing nalbuphine and tramadol.

BACKGROUND: Postoperative pain in ambulatory surgery is a multifactorial issue affecting patient satisfaction, time of discharge, and rehospitalization. This study evaluated the efficacy and safety of nalbuphine for the treatment of postoperative pain after ambulatory surgery, relative to tramadol. METHODS: This multi-center, randomized, double blind, and controlled study was conducted at 10 centers. In accordance with the inclusion criteria, 492 ambulatory surgery patients were recruited. These patients had moderate to severe pain after ambulatory surgery, with a visual analogue scale (VAS) score > 3 cm. They were randomly divided into an experimental (n = 248) or control (n = 244) group and treated for analgesia with 0.2 mg/kg of nalbuphine or 2 mg/kg of tramadol, respectively. VAS scores, adverse events, and vital signs of the patients were recorded before administration (baseline; T1); and 30 min (T2), 2 h (T3), 4 h (T4), and 6 h (T5) after administration of analgesia. A decrease in pain intensity of more than 25% compared with the baseline was used as an indicator of analgesic efficacy. The experimental and control groups were compared with regard to this indicator of efficacy at each timepoint. RESULTS: The VAS scores of the experimental and control groups were statistically comparable at timepoints T1-T4. At T5, the VAS scores of the experimental group were significantly lower than that of the control. The pain intensity was significantly higher in the experimental group compared with the control at T2 and T3. Adverse events and vital signs were similar for the two groups at each timepoint. CONCLUSIONS: Nalbuphine can provide effective and safe pain relief in patients after ambulatory surgery. TRIAL REGISTRATION: The registration number is ChiCTR-IOR-16010032 , the date of registration was 2016-11-28.

Nelarabine as salvage therapy and bridge to allogeneic stem cell transplant in 118 adult patients with relapsed/refractory T-cell acute lymphoblastic leukemia/lymphoma. A CAMPUS ALL study.

The outcome of relapsed or refractory (R/R) T-cell acute lymphoblastic leukemia/lymphoma (T-ALL/T-LBL) in adults is poor, with less than 20% of patients surviving at 5 years. Nelarabine is the only drug specifically approved for R/R T-ALL/T-LBL, but the information to support its use is based on limited available data. The aim of this observational phase four study was to provide recent additional data on the efficacy and safety of nelarabine in adults with R/R T-ALL/T-LBL and to evaluate the feasibility and outcome of allogeneic hematopoietic stem cell transplant (SCT) after salvage with nelarabine therapy. The primary endpoints were overall response rate (ORR) and overall survival (OS). Additional endpoints were safety, SCT rate and post-SCT OS. Between May 2007 and November 2018, 118 patients received nelarabine salvage therapy at 27 Italian hematology sites. The median age was 37 years (range 18-74 years), 73% were male, 77 had a diagnosis of T-ALL and 41 of T-LBL, and 65/118 (55%) had received more than two lines of therapy. The median number of nelarabine cycles was two (range 1-4); 43/118 (36%) patients had complete remission (CR), 16 had partial remission (14%) and 59 (50%) were refractory, with an ORR of 50%. The probability of OS, from the first dose of nelarabine, was 37% at 1 year with a median survival of 8 months. The OS at 1 year was significantly better for the 47 patients (40%) who underwent SCT after nelarabine salvage therapy (58% vs 22%, log-rank P < .001). The probability of OS at 2 and 5 years from SCT was 46% and 38%, respectively. Seventy-five patients (64%) experienced one or more drug-related adverse events (AE). Grade III-IV neurologic toxicities were observed in 9/118 (8%) of cases and thrombocytopenia or/and neutropenia (grade III-IV) were reported in 41% and 43% of cases, respectively. In conclusion, this is one of the largest cohorts of adult patients with R/R T-ALL/T-LBL treated in real life with nelarabine. Taking into account the poor prognosis of this patient population, nelarabine represents an effective option with an ORR of 50% and a CR rate of 36%. In addition, 40% of cases following nelarabine salvage therapy could undergo SCT with an expected OS at 2 and 5 years of 46% and 38%, respectively. The safety profile of nelarabine was acceptable with only 8% of cases showing grade III-IV neurological AE.

The 95% effective dose of nalbuphine in patient-controlled intravenous analgesia for patients undergoing laparoscopic total hysterectomy compared to equivalent sufentanil.

PURPOSE: To evaluate the 95% effective dose of nalbuphine in patient-controlled intravenous analgesia (PCIA) by the sequential method and compare the analgesia efficacy with the equivalent dose of sufentanil on patients undergoing laparoscopic total hysterectomy. METHODS: In the first part, we defined a successful analgesia as the highest VAS ≤3 in 24 hours postoperatively. On the contrary, a failed analgesia was the highest VAS>3. According to the last patient's outcome, the next patients would be given an increase or decreased dose grade. This process ended up with 9 cross-over points. In the second part, 60 patients undergoing laparoscopic total hysterectomy were selected. They were randomly divided into 2 groups (n = 30 each group): receiving sufentanil 1.78 µg/kg (group S) and nalbuphine 1.78 mg/kg (group N). PCIA pump was given at the end of the operation with 5 mL bonus loading. The total amount of PCIA was 100 mL and programmed to deliver 0.5 mL each time with a lockout interval of 15 minutes and the background infusion amount of 2 mL/h. The VAS score and Ramsay score of were collected after the operation, the number of effective pressing times of PCIA were also recorded. Adverse reactions were documented in detail. RESULTS: The 95% effective dose of nalbuphine in PCIA on patients undergoing laparoscopic total hysterectomy was 1.78 mg/kg. There was no significant difference in VAS between the sufentanil group and the nalbuphine groups (P > .05), but the number of the use of PCIA in the group S was more than that in the group N obviously (P <.05). The group S has a lower ramsay sedation score than group N at every time point. (P <.05). The incidence of nausea and vomiting was not statistically significant differences between two groups in the first 24 hours after colonoscopy (P >  q .05). CONCLUSION: Nalbuphine 1.78 mg/kg in PCIA is recommended for the patients undergoing laparoscopic total hysterectomy. And nalbuphine is a reasonable alternative to sufentanil when used in PCIA.

A comparative study of three concentrations of intravenous nalbuphine combined with hydromorphone for post-cesarean delivery analgesia.

BACKGROUND: Nalbuphine has been suggested to be used for post-cesarean section (CS) intravenous analgesia. However, ideal concentration of nalbuphine for such analgesia remains unclear. The present study was conducted to explore an ideal concentration of nalbuphine for post-CS intravenous analgesia by evaluating the analgesic effects and side-effects of three different concentrations of nalbuphine combined with hydromorphone for post-CS intravenous analgesia in healthy parturients. METHODS: One-hundred-and-fourteen parturients undergoing elective CS were randomly allocated to one of three groups (38 subjects per group) according to an Excel-generated random number sheet to receive hydromorphone 0.05 mg/mL + nalbuphine 0.5 mg/mL (group LN), hydromorphone 0.05 mg/mL + nalbuphine 0.7 mg/mL (group MN), and hydromorphone 0.05 mg/mL + nalbuphine 0.9 mg/mL (group HN) using patient-controlled analgesia (PCA) pump. Visual analog scale (VAS) for pain, PCA bolus demands, cumulative PCA dose, satisfaction score, Ramsay score, and side-effects such as urinary retention were recorded. RESULTS: The number of PCA bolus demands and cumulative PCA dose during the first 48 h after CS were significantly higher in group LN (21 ±â€Š16 bolus, 129 ±â€Š25 mL) than those in group MN (15 ±â€Š10 bolus, 120 ±â€Š16 mL) (both P < 0.05) and group HN (13 ±â€Š9 bolus, 117 ±â€Š13 mL) (both P < 0.01), but no difference was found between group HN and group MN (both P > 0.05). VAS scores were significantly lower in group HN than those in group MN and group LN for uterine cramping pain at rest and after breast-feeding within 12 h after CS (all P < 0.01) and VAS scores were significantly higher in group LN than those in group MN and group HN when oxytocin was intravenously infused within 3 days after CS (all P < 0.05), whereas VAS scores were not statistically different among groups for incisional pain (all P > 0.05). Ramsay sedation scale score in group HN was significantly higher than that in group MN at 8 and 12 h after CS (all P < 0.01) and group LN at 4, 8, 12, 24 h after CS (all P < 0.05). CONCLUSIONS: Hydromorphone 0.05 mg/mL + nalbuphine 0.7 mg/mL for intravenous PCA could effectively improve the incisional pain and uterine cramping pain management and improve comfort in patients after CS. TRIAL REGISTRATION NUMBER: ChiCTR1800015014, http://www.chictr.org.cn/ Chinese Clinical Trial Registry.

Total intravenous anesthesia in domestic chicken (Gallus gallus domesticus) with propofol alone or in combination with methadone, nalbuphine or fentanyl for ulna osteotomy.

OBJECTIVE: To compare the propofol infusion rate and cardiopulmonary effects during total intravenous anesthesia with propofol alone and propofol combined with methadone, fentanyl or nalbuphine in domestic chickens undergoing ulna osteotomy. STUDY DESIGN: Prospective, randomized, experiment trial. ANIMALS: A total of 59 healthy Hissex Brown chickens weighing 1.5 ± 0.2 kg. METHODS: Anesthesia was induced with propofol (9 mg kg-1) administered intravenously (IV) and maintained with propofol (1.2 mg kg-1 minute-1) for 30 minutes. Birds were intubated and supplemented with 100% oxygen through a nonrebreathing circuit under spontaneous ventilation. Thereafter, each animal was randomly assigned to one of four groups: group P, no treatment; group PM, methadone (6 mg kg-1) intramuscularly (IM); group PN, nalbuphine IM (12.5 mg kg-1); and group PF, fentanyl IV (30 µg kg-1 loading dose, 30 µg kg-1 hour-1 constant rate infusion). During the osteotomy surgery, the propofol infusion rate was adjusted to avoid movement of birds and provide adequate anesthesia. Pulse rate, invasive blood pressure, respiratory frequency, end-tidal carbon dioxide partial pressure (Pe'CO2) and hemoglobin oxygen saturation (SpO2) were recorded. RESULTS: Data were available from 58 chickens. The mean ± standard deviation propofol infusion rate (mg kg-1 minute-1) for the duration of anesthesia was: group P, 0.81 ± 0.15; group PM, 0.66 ± 0.11; group PN, 0.60 ± 0.14; and group PF, 0.80 ± 0.07. Significant differences were P versus PM (p = 0.042), P versus PN (p = 0.002) and PF versus PN (p = 0.004). Pulse rate, blood pressure and SpO2 remained acceptable for anesthetized birds with minor differences among groups. Values of Pe'CO2 >60 mmHg (8 kPa) were observed in all groups. CONCLUSIONS AND CLINICAL RELEVANCE: Methadone and nalbuphine, but not fentanyl, decreased the propofol infusion rate required for anesthesia maintenance, but resulted in no obvious benefit in physiological variables.

Use of nalbuphine as a substitute for butorphanol in combination with dexmedetomidine and tiletamine/zolazepam: a randomized non-inferiority trial.

OBJECTIVES: The goal of this study was to determine whether a drug combination using nalbuphine with dexmedetomidine and tiletamine/zolazepam is non-inferior to one that uses butorphanol. METHODS: All healthy cats presenting solely for gonadectomy to two trap-neuter-return mobile clinic days were randomly assigned to induction with a combination of tiletamine/zolazepam 3 mg/kg, dexmedetomidine 7.5 µg/kg and either butorphanol or nalbuphine at 0.15 mg/kg. All participants were blinded to the identity of the combinations. The primary endpoint was clinician satisfaction, comprised of the mean of four satisfaction ratings on a 7-point Likert scale (highly dissatisfied through to highly satisfied) recorded for induction, maintenance of anesthesia, surgery and recovery. Exploratory endpoints included each individual score, number of injections, duration of induction, duration of recovery and need for reversal agent. To assess non-inferiority for the primary endpoint and individual scores, the difference and 95% confidence intervals (CIs) of the difference between the mean clinical scores for the nalbuphine and butorphanol-based combinations were calculated and compared with a prespecified non-inferiority margin of 20% (1.4 points). RESULTS: Seventy-two cats were enrolled, 36 in each group. The mean ± SD composite score for the combination with nalbuphine was 6.06 ± 0.59 (95% CI 5.86-6.25) points, while the combination with butorphanol was 6.22 ± 0.62 (95% CI 6.01-6.43). The difference between mean scores was 0.17 (-0.12 to 0.45), which did not exceed the prespecified boundary of 1.4, establishing the non-inferiority of nalbuphine. No individual clinical score for nalbuphine was inferior to butorphanol, and there were no significant differences for any secondary endpoints. CONCLUSIONS AND RELEVANCE: The clinical experience of the nalbuphine-based combination was non-inferior to the butorphanol-based combination. Nalbuphine is an effective substitute for butorphanol, providing another option if butorphanol is unavailable due to shortage, controlled status or cost, without requiring a change in anesthetic workflow.