Effective Dose of Dexmedetomidine with Nalbuphine Hydrochloride or Butorphanol Tartrate for Sedation in Buff Orpington Hens (Gallus gallus domesticus).

Chickens (Gallus gallus domesticus) are commonly used for research, food production, show, and companionship. Sedation is often necessary for sample collection, imaging, or treatment. Dexmedetomidine has been previously used to sedate birds, often with other sedatives. Butorphanol tartrate, a Schedule IV controlled substance, is commonly used but presents regulatory challenges. Nalbuphine hydrochloride, an opioid with similar receptor affinity to butorphanol, has potential as a noncontrolled alternative. Although information regarding nalbuphine use in birds is limited, its noncontrolled status makes it more accessible. The purpose of this study was to determine the effective dose to produce sedation in 50% (ED50) of patients and to estimate the calculated effective dose of dexmedetomidine in combination with either butorphanol (DexBut) or nalbuphine (DexNal) in domestic hens to sedate 99% of patients (ED99). Eighteen 33-week-old laying Buff Orpington hens were divided into 2 groups: one receiving DexBut (n = 9) and the second receiving DexNal (n = 9). Each hen was sedated with varying doses of intramuscular dexmedetomidine with a constant dose of either 2 mg/kg IM butorphanol or 12.5 mg/kg IM nalbuphine by an up-and-down design. Sedation was determined using a clinically applicable scoring system. The ED50 values of dexmedetomidine with 2 mg/kg IM of butorphanol, calculated by both the up-and-down method and logistic regression, were 38 and 49 µg/kg, respectively, while the ED50 values of dexmedetomidine in combination with 12.5 mg/kg IM of nalbuphine were 19 and 18 µg/kg, respectively. The estimated dexmedetomidine ED99 values with butorphanol or nalbuphine were 51 and 19 µg/kg, respectively. Multiple chickens in both groups exhibited open-mouth breathing and comb pallor but no lasting morbidity or mortality occurred. Combinations of DexBut or DexNal should be considered for sedation of domestic chickens.

Effect of Ropivacaine Combined with Nalbuphine on Pain during Anaesthesia Recovery in Patients with Prostatic Hyperplasia Undergoing Transurethral Resection of Prostate.

BACKGROUND: As a frequent disease, prostatic hyperplasia could be treated by transurethral resection of prostate (TURP). However, postoperative pain may affect the prognosis of patients to some extent, so exploring reasonable anaesthetic drugs is an important measure to reduce the recovery period of anaesthesia. This study used the combination of ropivacaine and nalbuphine for intraoperative anaesthesia in patients undergoing TURP to investigate its effect on pain during anaesthesia recovery. METHODS: A retrospective study was conducted on the clinical data of 205 patients with prostatic hyperplasia who underwent TURP in our hospital from June 2020 to December 2022. All patients experienced epidural anaesthesia, and 110 patients who used ropivacaine combined with nalbuphine were included in the study group, whereas 95 patients who used ropivacaine and lidocaine were classified as the control group. The Visual Analogue Scale was used to evaluate the pain conditions of patients. The levels of pain mediators, such as substance P (SP), bradykinin (BK) and histamine (HIS), the stress levels, including cortisol (Cort), adrenocorticotropic hormone (ACTH) and norepinephrine (NE), and the incidence of adverse reactions were compared between the two groups. RESULTS: At T0 (postoperative 30 min), T1 (postoperative 60 min), T2 (postoperative 2 h) and T3 (postoperative 4 h), the study group had significantly lower pain scores (p < 0.01), levels of SP, BK and HIS (p < 0.001), and levels of Cort, ACTH and NE (p < 0.05) than the control group. No statistical difference was observed in the incidences of adverse reactions between the two groups (p > 0.05). CONCLUSIONS: The combination of ropivacaine and nalbuphine has a notable analgesic effect during anaesthesia recovery in patients undergoing TURP. It inhibits the secretion of pain and physical stress indicators and relieves postoperative pain to a large extent.

Alternative Reinforcers Enhance the Effects of Opioid Antagonists, but Not Agonists, on Oxycodone Choice Self-Administration in Nonhuman Primates.

Clinical reports suggest that the most effective strategies for managing opioid use disorder comprise a comprehensive treatment program of both pharmacological and nonpharmacological approaches. However, the conditions under which these combinations are most effective are not well characterized. This study examined whether the presence of an alternative reinforcer could alter the efficacy of Food and Drug Administration-approved opioid antagonist or agonist medications, as well as the nonopioid flumazenil, in decreasing oxycodone choice self-administration in nonhuman primates. Adult squirrel monkeys (n = 7; four females) responded under concurrent second-order fixed-ratio (FR)-3(FR5:S);TO45s schedules of reinforcement for intravenous oxycodone (0.1 mg/kg) or saline on one lever and 30% sweetened condensed milk or water on the other. Doses of naltrexone (0.00032-1.0 mg/kg), nalbuphine (0.32-10 mg/kg), buprenorphine (0.0032-0.032 mg/kg), methadone (0.32-1.0 mg/kg), or flumazenil (1-3.2 mg/kg) were administered intramuscularly prior to oxycodone self-administration sessions that occurred with either milk or water as the alternative. Naltrexone, a µ-opioid receptor antagonist, was >30-fold more potent when milk was available compared with water and abolished oxycodone intake (injections/session) while concomitantly increasing milk deliveries at the highest dose tested. Pretreatment with the low-efficacy µ-agonist nalbuphine was most effective in the presence of milk compared with water, decreasing oxycodone preference to <50% of control values. The higher efficacy µ-agonists, methadone and buprenorphine, and the benzodiazepine antagonist flumazenil did not appreciably alter the reinforcing potency of oxycodone under either condition. These results suggest that antagonist medications used in combination with alternative reinforcers may be an effective strategy to curtail opioid abuse-related behaviors. SIGNIFICANCE STATEMENT: Clinical treatment programs for opioid use disorder use a combination of pharmacological and nonpharmacological approaches. However, the conditions under which these combinations are most effective have not been fully characterized. This study examined whether the effectiveness of µ-opioid medications to decrease oxycodone self-administration is altered in the presence of an alternative reinforcer. The results suggest that alternative reinforcers enhance the effects of antagonist or low-efficacy partial agonists, suggesting they may be a more effective strategy to curtail opioid use.

Comparison of Butorphanol-Azaperone-Medetomidine and Nalbuphine-Medetomidine-Azaperone in Free-Ranging Elk (Cervus canadensis) in Pennsylvania, USA.

Chemical immobilization is commonly used to capture and handle free-ranging elk (Cervus canadensis). Butorphanol-azaperone-medetomidine (BAM) and nalbuphine-medetomidine-azaperone (NalMed-A) are compounded drug combinations that are lower-scheduled in the US than drugs historically used for elk immobilizations. We compared BAM and NalMed-A for immobilization of free-ranging elk using free-darting and Clover trapping. From January 2020 to April 2022, 196 female elk were immobilized in Pennsylvania, USA. We report vital rates, induction and recovery times, and the need for supplemental drugs. We built mixed-effects logistic regression models to describe differences between drug choice based on induction and recovery times, capture method, and individual variation. Several models were competing, including our null model, which suggests that BAM and NalMed-A are comparable based on the parameters we evaluated. Supplemental drug administration was more frequently needed in NalMed-A immobilizations (21.2%) than in BAM immobilizations (9.0%). Overall, we found minor differences between BAM and NalMed-A, both of which appear to be effective for immobilizing elk in both free-darting and Clover trapping scenarios when performing moderately invasive, minimally painful procedures on free-ranging elk.

[Prehospital analgesia with nalbuphine and paracetamol compared to piritramide by paramedics-A multicenter observational study]. / Prähospitale Analgesie mit Nalbuphin und Paracetamol im Vergleich zu Piritramid durch Notfallsanitäter*innen ­ eine multizentrische Observationsstudie.

OBJECTIVE: Following recent changes to the German Narcotics Act, this article examines prehospital analgesia by paramedics using piritramide vs. nalbuphine + paracetamol. MATERIAL AND METHODS: Prehospital analgesia administered by paramedics from the Fulda (piritramide) and Gütersloh (nalbuphine + paracetamol) emergency services was compared regarding pain intensity at the beginning and end of the mission, measured using the numeric rating scale (NRS). Additionally, an analysis of the resulting complications was carried out. RESULTS: In this study 2429 administrations of analgesia were evaluated (nalbuphine + paracetamol: 1635, 67.3%, initial NRS: 8.0 ± 1.4, end of NRS: 3.7 ± 2.0; piritramide: 794, 32.7%, initial NRS: 8.5 ± 1.1, end of NRS: 4.5 ± 1.6). Factors influencing NRS change were initial NRS (regression coefficient, RC: 0.7075, 95% confidence interval, CI: 0.6503-0.7647, p < 0.001), treatment with nalbuphine + paracetamol (RC: 0.6048, 95% CI: 0.4396-0.7700, p < 0.001). Treatment with nalbuphine + paracetamol (n = 796 (48.7%)) compared to piritramide (n = 190 (23.9%)) increased the odds of achieving NRS < 4 (odds ratio, OR: 2.712, 95% CI: 2.227-3.303, p < 0.001). Complications occurred in n = 44 (5.5%) with piritramide and in n = 35 (2.1%) with nalbuphine + paracetamol. Risk factors for complications were analgesia with piritramide (OR: 2.699, 95% CI: 1.693-4.301, p < 0.001), female sex (OR: 2.372, 95% CI: 1.396-4.029, p = 0.0014), and age (OR: 1.013, 95% CI: 1.002-1.025, p = 0.0232). CONCLUSION: Compared with piritramide, prehospital analgesia with nalbuphine + paracetamol has favorable effects in terms of analgesic efficacy and complication rates and should therefore be considered in future recommendations for paramedics.

The effect of nalbuphine on prevention of emergence delirium in children: a systematic review with meta-analysis.

BACKGROUND: Emergence delirium remains a major postoperative concern for children undergoing surgery. Nalbuphine is a synthetic mixed agonist-antagonist opioid, which is believed to reduce the incidence of emergence delirium in children. The primary objective was to examine the effect of nalbuphine on emergence delirium in children undergoing surgery. METHODS: Databases of MEDLINE, EMBASE, and CENTRAL were searched from their starting dates until April 2023. Randomized Clinical Trials (RCT) and observational studies comparing nalbuphine and control in children undergoing surgery were included. RESULTS: Eight studies (n = 1466 patients) were eligible for inclusion of data analysis. Compared to the control, our pooled data showed that the nalbuphine group was associated with lower incidence of emergence delirium (RR = 0.38, 95% CI [0.30, 0.47], p < 0.001) and reduced postoperative pain scores (MD = -0.98, 95% CI [-1.92, -0.04], p = 0.04). CONCLUSIONS: This review showed the administration of nalbuphine is associated with significant decrease in the incidence of emergence delirium and postoperative pain scores among children undergoing surgery. However, due to limited sample size, high degree of heterogeneity and low level of evidence, future adequately powered trials are warranted to explore the efficacy of nalbuphine on emergence delirium among the pediatric population.

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.

A Continuous Intestinal Absorption Model to Predict Drug Enterohepatic Recirculation in Healthy Humans: Nalbuphine as a Model Substrate.

Nalbuphine (NAL) is a κ-agonist/µ-antagonist opioid being developed as an oral extended formulation (ER) for the treatment of chronic cough in idiopathic pulmonary fibrosis and itch in prurigo nodularis. NAL is extensively glucuronidated and likely undergoes enterohepatic recirculation (EHR). The purpose of this work is to develop pharmacokinetic models for NAL absorption and enterohepatic recirculation (EHR). Clinical pharmacokinetic (PK) data sets in healthy subjects from three trials that included IV, oral solution, and ER tablets in fed and fasted state and two published trials were used to parametrize a novel partial differential equation (PDE)-based model, termed "PDE-EHR" model. Experimental inputs included in vitro dissolution and permeability data. The model incorporates a continuous intestinal absorption framework, explicit liver and gall bladder compartments, and compartments for systemic drug disposition. The model was fully PDE-based with well-stirred compartments achieved by rapid diffusion. The PDE-EHR model accurately reproduces NAL concentration-time profiles for all clinical data sets. NAL disposition simulations required inclusion of both parent and glucuronide recirculation. Inclusion of intestinal P-glycoprotein efflux in the simulations suggests that NAL is not expected to be a victim or perpetrator of P-glycoprotein-mediated drug interactions. The PDE-EHR model is a novel tool to predict EHR and food/formulation effects on drug PK. The results strongly suggest that even intravenous dosing studies be conducted in fasted subjects when EHR is suspected. The modeling effort is expected to aid in improved prediction of dosing regimens and drug disposition in patient populations.

Nalbuphine versus morphine: an adjuvant to spinal anesthesia for controlling pain after total knee arthroplasty: a propensity score-matched analysis.

BACKGROUND: Nalbuphine, a synthetic k-agonist and µ-antagonist, provides efficient pain relief while reducing opioid-related adverse effects. This study aims to compare the efficacy of intrathecal nalbuphine (ITN) with intrathecal morphine (ITM) for post-TKA pain. METHODS: A retrospective cohort analysis of 131 patients who underwent TKA with spinal anesthesia (SA), a single shot of adductor canal block, and periarticular injections was conducted. The patients were divided into 2 groups, Group N received 0.8 mg nalbuphine, and Group M received 0.2 mg morphine as an adjuvant to SA. Propensity-score matching was employed to compare the visual analog scales (VAS) of postoperative pain intensity, cumulative morphine use (CMU), maximum knee flexion angle, straight leg raise (SLR) ability, incidence of postoperative nausea and vomiting (PONV), and length of hospital stay (LHS). RESULTS: The mean VAS of group M were significantly lower than group N at 6, 12, 18, and 24 h (P < 0.01). Group M had lower CMU than group N at 24 h (P < 0.01) and 48 h (P < 0.01), while there was no significant difference between groups in terms of knee flexion angle and SLR at any time point. Additionally, 29.3 and 57.9% of patients in group N and M experienced PONV, respectively (p = 0.04), and group N had significantly shorter LHS compared to group M (P < 0.001). CONCLUSION: Although, intrathecal morphine (ITM) still provides better pain control particularly in the first 24 h, patients who received intrathecal nalbuphine (ITN) had significantly fewer incidence of PONV, and shorter LHS.

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.

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.

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).

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.