Efficacy and safety of nalbuphine for epidural labor analgesia at high altitude: An observational study.

Xining is located at the eastern edge of the Qinghai-Tibet Plateau, with an average altitude of >7000 feet (>2000 m). Nalbuphine is a kappa-opioid receptor agonist that can provide analgesia with fewer side effects than other opioid analgesics. This study aimed to evaluate pain control, side effects, and neonatal outcomes from combining nalbuphine with sufentanil and ropivacaine in 600 women during epidural anesthesia while giving birth at a high altitude in Xining, China. A total of 600 parturients receiving epidural labor analgesia were randomly divided into 2 groups, each group 300 parturients. The nalbuphine group received nalbuphine, sufentanil, and ropivacain, the control group only received sufentanil and ropivacain. The analgesic effect was evaluated through the Visual Analogue Scale scores. Neonatal outcomes were mainly evaluated through the Apgar Scores. Compared to the control group, the nalbuphine group showed lower Visual Analogue Scale scores at all time points after analgesia (P < .05). In comparison with the control group, parturients in the nalbuphine group showed lower incidence rates of fever at delivery, 24-hour postpartum bleeding, and pruritus (P < .05). However, between the 2 groups, there were no statistically significant differences in the remaining maternal and infant outcomes and neonatal outcomes (P > .05). Moreover, no adverse effects on neonatal outcomes were observed. The findings from this study support findings from previous studies that nalbuphine provided safe epidural analgesia without significant side effects for the mother and infant, and showed both safety and efficacy when used during labor at high altitude.

Optimal Post-Operative Nalbuphine Dose Regimen: A Randomized Controlled Trial in Patients with Laparoscopic Cholecystectomy.

Background and Objectives: Optimal opioid analgesia is an excellent analgesia that does not present unexpected adverse effects. Nalbuphine, acting on the opioid receptor as a partial mu antagonist and kappa agonist, is considered a suitable option for patients undergoing laparoscopic surgery. Therefore, we aim to investigate the appropriate dosage of nalbuphine for post-operative pain management in patients with laparoscopic cholecystectomy. Materials and Methods: Patients were randomly categorized into low, medium, and high nalbuphine groups. In each group, a patient control device for post-operative pain control was programed with a low (0.05 mg/kg), medium (0.10 mg/kg), or high (0.20 mg/kg) nalbuphine dose as a loading dose and each bolus dose with a lockout interval of 7 min and without background infusion. Primary and secondary outcomes included the post-operative pain scale and nalbuphine consumption, and episodes of post-operative opioid-related adverse events and satisfactory scores. Results: The low-dosage group presented a higher initial self-reported pain score in comparison to the other two groups for the two hours post-op (p = 0.039) but presented lower nalbuphine consumption than the other two groups for four hours post-op (p = 0.047). There was no significant difference in the analysis of the satisfactory score and adverse events. Conclusions: An appropriate administration of nalbuphine could be 0.1 to 0.2 mg/kg at the initial four hours; this formula could be modified to a lower dosage (0.05 mg/kg) in the post-operative management of laparoscopic cholecystectomy.

Effect of two different doses of nalbuphine for postoperative analgesia in children with cleft palate: a randomized controlled trial.

BACKGROUND: Cleft palate repair surgery may result in severe pain in the immediate postoperative period. The aim of this study is to compare the effects of different doses of nalbuphine for postoperative analgesia in children with cleft palate. METHODS: From November 2019 to June 2021, 90 children (45 males and 45 females, age 9-20 months old, ASA class I-II) were selected for palatoplasty. They were randomly divided into three groups: the control group (Group C), the N1 group (postoperative analgesia with 0.05 mg/kg/h nalbuphine) and the N2 group (postoperative analgesia with 0.075 mg/kg/h nalbuphine). Each group had 30 cases. Nalbuphine was not continuously infused in Group C but was continuously infused in Groups N1 and N2 at rates of 0.05 mg/kg/h and 0.075 mg/kg/h, respectively, for 24 h for postoperative analgesia. The FLACC analgesia score and Ramsay Sedation score were recorded at 10 min (T1), 30 min (T2), 2 h (T3), 12 h (T4) and 24 h (T5) after the operation. Adverse reactions such as nausea, vomiting and respiratory depression were observed and recorded. RESULTS: Compared with those in Group C, the FLACC scores in the N1 and N2 groups decreased significantly at T1-T5 (p < 0.05); the Ramsay Sedation score in the N1 group was significantly higher at T3 and T4 (p < 0.05), and that in the N2 group was significantly higher at T1-T5 (p < 0.05). Compared with that in the N1 group, the FLACC score in the N2 group was not significantly different, and the Ramsay Sedation score increased significantly at T5 (p < 0.05). CONCLUSION: Using 0.05 mg/kg/h Nalbuphine continuously for 24 h for postoperative analgesia in children with cleft palate has a better effect and fewer adverse reactions. TRIAL REGISTRATION: This study was registered at ChiCTR1900027385 (11/11/2019).

Nalbuphine-6-glucuronide is a potent analgesic with superior safety profiles by altering binding affinity and selectivity for mu-/kappa-opioid receptors.

Although nalbuphine, a semi-synthetic analgesic compound, is less potent than morphine in terms of alleviating severe pain, our recent findings have revealed that nalbuphine-6-glucuronide (N6G), one of the glucuronide metabolites of nalbuphine, promotes a significantly more robust analgesic effect than its parent drug. Nevertheless, despite these promising observations, the precise mechanisms underlying the analgesic effects of nalbuphine glucuronides have yet to be determined. In this study, we aim to elucidate the mechanisms associated with the analgesic effects of nalbuphine glucuronides. Pharmacokinetic and pharmacodynamic studies were conducted to investigate the relationship between the central and peripheral compartments of nalbuphine and its derivatives. The analgesic responses of these compounds were evaluated based on multiple behavioral tests involving thermal and mechanical stimuli. Radioligand binding assays were also performed to determine the binding affinity and selectivity of these compounds for different opioid receptors. The results of these tests consistently confirmed that the heightened analgesic effects of N6G are mediated through its enhanced binding affinity for both mu- and kappa-opioid receptors, even comparable to those of morphine. Notably, N6G exhibited fewer side effects and did not induce sudden death, thereby highlighting its superior safety profile. Additionally, pharmacokinetic studies indicated that N6G could cross the blood-brain barrier when administered peripherally, offering pain relief. Overall, N6G provides great analgesic efficacy and enhanced safety. These findings highlight the potential value of nalbuphine glucuronides, particularly N6G, as promising candidates for the development of novel analgesic drugs.

Butorphanol-Azaperone-Medetomidine Is as Safe and Effective as Nalbuphine-Azaperone-Medetomidine for Immobilization of Juvenile American Black Bears (Ursus americanus).

Immobilization kits including butorphanol-azaperone-medetomidine (BAM) and nalbuphine-azaperone-medetomidine can provide effective, safe, and easy-to-use protocols in bears. Nalbuphine-azaperone-medetomidine is not commercially available but may be useful for wildlife agencies because it does not contain controlled substances. This study directly compared BAM to nalbuphine-azaperone-medetomidine immobilization in 10 juvenile healthy black bears (10 mo old; four females, six males) undergoing prerelease examinations after rehabilitation. Bears were immobilized via remote delivery of 1 mL of BAM (n=5) or nalbuphine-azaperone-medetomidine (n=5) intramuscularly in the shoulder during December (randomized, blinded trial). Bears were intubated, monitored with an electrocardiogram, pulse oximeter, capnograph, noninvasive blood pressure cuff, and rectal thermometer, and underwent physical examination, sample collection, morphometrics, and ear-tag placement. Induction, physiologic, and recovery parameters were recorded, including arterial blood gas analysis. The anesthetic agents were antagonized with atipamezole and naltrexone. There were no differences between protocols in induction or recovery times. There were no differences between protocols in heart rate, respiratory rate, temperature, oxygen saturation, end-tidal CO2, mean arterial pressure, or blood gas analysis or any differences between male and female bears in any parameters. Bears were hypertensive and normoxemic with low oxygen saturation via pulse oximeter, but all recovered smoothly and were released within 2 h of recovery. This study supports that nalbuphine-azaperone-medetomidine is clini-cally as safe and effective as BAM in American black bears.

Comparison of Ketamine-Xylazine, Butorphanol-Azaperone-Medetomidine, and Nalbuphine-Medetomidine-Azaperone for Raccoon (Procyon lotor) Immobilization.

Raccoons (Procyon lotor) are frequently handled using chemical immobilization in North America for management and research. In a controlled environment, we compared three drug combinations: ketamine-xylazine (KX), butorphanol-azaperone-medetomidine (BAM), and nalbuphine-medetomidine-azaperone (NalMed-A) for raccoon immobilization. In crossover comparisons, raccoons received a mean of the following: 8.66 mg/kg ketamine and 1.74 mg/kg xylazine (0.104 mL/kg KX); 0.464 mg/kg butorphanol, 0.155 mg/kg azaperone, and 0.185 mg/kg medetomidine (0.017 mL/kg BAM); and 0.800 mg/kg nalbuphine, 0.200 mg/kg azaperone, and 0.200 mg/kg medetomidine (0.020 mL/kg NalMed-A). Induction time was shortest with KX (mean±SE, 10.0±0.7 min) and longest with NalMed-A (13.0±1.3 min). A sampling procedure was completed on 89% (16/18), 72% (13/18), and 89% (16/18) of the raccoons administered KX, BAM, and NalMed-A, respectively. Reasons for incomplete sampling included inadequate immobilization (one KX and one NalMed-A), responsive behaviors (one each with KX, BAM, NalMed-A), or animal safety (four BAM). Mean recovery time for KX was 32.8±7.1 min without antagonizing and 28.6±5.2 min following delivery of an antagonist. Mean recovery time was 6.2±0.8 min for BAM and 5.1±0.5 min for NalMed-A after antagonizing. Only with KX were raccoons observed to recover without use of an antagonist. Supplemental oxygen was provided to 23% (3/13), 72% (13/18), and 71% (12/17) of raccoons immobilized with KX, BAM, and NalMed-A, respectively. Hypoxemia at <80% oxygen saturation occurred in 0% (0/17), 27% (4/15), and 6% (1/16) of the raccoons administered KX, BAM, and NalMed-A, respectively; all raccoons fully recovered from chemical immobilization. All combinations could be used for raccoon immobilization; however, the need for delivery of supplemental oxygen to a majority of raccoons immobilized with BAM and NalMed-A may limit broader use of these agents for certain field studies involving capture, sample, and release of free-ranging animals from a practical standpoint.

Epidural nalbuphine versus dexmedetomidine as adjuvants to bupivacaine in lower limb orthopedic surgeries for postoperative analgesia: a randomized controlled trial.

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.

Effectiveness and safety of prehospital analgesia including nalbuphine and paracetamol by paramedics: an observational study.

BACKGROUND: The aim of this study was to examine the effectiveness and safety of prehospital analgesia with nalbuphine and/or paracetamol by paramedics. METHODS: In this retrospective trial, following the implementation of a standard-operating-procedure for pain requiring treatment as defined as a score ≥4 on the 0-10 Numeric Rating Scale for pain, all emergency operations in the district of Gütersloh between January 1, 2020, and June 30, 2022, with analgesic administration by paramedics in patients ≥18 years were included in the study. Analgesic agents employed by the paramedics included nalbuphine and/or paracetamol, butylscopolamine for abdominal colic, and esketamine in case of failure of the other analgesics. The primary endpoint was the patients' rating of their pain on the Numeric Rating Scale at the end of the operation. Additional covariates included sex, cause of pain, analgesics used, Numeric Rating Scale at beginning and analgesic-associated complications (reduced level of consciousness, hypotension, desaturation, a- or bradypnea). RESULTS: A total of 1931 emergency operations (female: N.=1039 [53.8%]) with pain requiring treatment (non-traumatic cause: N.=1106 [57.3%]; initial Numeric Rating Scale: 8.0±1.4). Analgesics applied were nalbuphine + paracetamol (50.6%), paracetamol (38.7%), butylscopolamine (13.4%), nalbuphine (7.7%), and esketamine (4.9%). Mean pain reduction was 4.3±2.3 (nalbuphine + paracetamol: 5.0±2.1; nalbuphine: 4.7±2.3) and paracetamol: 3.3±2.2, respectively. Factors influencing a change in the Numeric Rating Scale were trauma (regression-coefficient: -0.308, 95% CI: -0.496 - -0.119, P=0.0014 vs. non-trauma; nalbuphine [yes vs. no]: regression-coefficient 0.684, 95% CI 0.0774-1.291, P=0.03; nalbuphine + paracetamol: regression-coefficient 0.763, 95% CI 0.227-1.299, P=0.005). At the end of the operation, 49.7% had a Numeric Rating Scale <4, 34.3% had a Numeric Rating Scale 4-5, and 16.0% had a Numeric Rating Scale ≥6. Factors influencing a Numeric Rating Scale <4 at end of use were trauma vs. non-trauma: odds ratio 0.788, 95% CI 0.649-0.957, P=0.02. The Numeric Rating Scale at beginning reported: odds ratios 0.754, 95% CI 0.700-0.812, P<0.0001. Analgesic-associated complications were not observed. CONCLUSIONS: Prehospital analgesia by paramedics with nalbuphine as monotherapy or in combination with paracetamol allows for sufficient analgesia without the occurrence of complications.

Analgesic Efficacy of Nalbuphine as an Adjuvant to Ropivacaine in Erector Spinae Plane Block for Percutaneous Nephrolithotomy: A Randomized, Double-Blinded, Clinical Trial.

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: Patients scheduled for PCNL were randomized into three groups and received ultrasound-guided ESPB at T10 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.

A MIXTURE OF NALBUPHINE, AZAPERONE, AND MEDETOMIDINE FOR IMMOBILIZING RINGTAILS (BASSARISCUS ASTUTUS).

We evaluated a combination of nalbuphine HCl (40 mg/mL), azaperone tartrate (10 mg/mL), and medetomidine HCl (10 mg/mL), a combination known as NAM or NalMed-A, in 23 ringtails (Bassariscus astutus) during 29 handling events for a radio-collaring study in southern Oregon, US, from August 2020 to March 2022. The combination was delivered to ringtails by hand injection at 0.075 mL NAM per estimated 1 kg body mass. The mean (± standard deviation, SD) dosage calculated post hoc was 3.366 (±0.724) mg/kg nalbuphine, 0.841 (±0.181) mg/kg medetomidine, and 0.841 (±0.181) mg/kg azaperone. All captured ringtails were effectively immobilized with a mean (SD) induction time of 13.24 (±3.57) min. The medetomidine and nalbuphine components were antagonized with a combination of atipamezole and naltrexone HCl with a mean (SD) recovery time of 2.48 (±1.94) min. This combination appeared to be safe and effective for immobilizing ringtails with a low volume dose, smooth antagonism, and rapid recovery. In addition, NAM does not contain any drugs that are US Drug Enforcement scheduled, which makes it useful for immobilization procedures by wildlife professionals in the US.

Application of analgesics in emergency services in Germany: a survey of the medical directors.

ABSTRAC: BACKGROUND: Treatment of acute pain is an essential element of pre-hospital care for injured and critically ill patients. Clinical studies indicate the need for improvement in the prehospital analgesia. OBJECTIVE: The aim of this study is to assess the current situation in out of hospital pain management in Germany regarding the substances, indications, dosage and the delegation of the use of analgesics to emergency medical service (EMS) staff. MATERIAL AND METHODS: A standardized survey of the medical directors of the emergency services (MDES) in Germany was carried out using an online questionnaire. The anonymous results were evaluated using the statistical software SPSS (Chi-squared test, Mann-Whitney-U test). RESULTS: Seventy-seven MDES responsible for 989 rescue stations and 397 EMS- physician bases in 15 federal states took part in this survey. Morphine (98.7%), Fentanyl (85.7%), Piritramide (61%), Sufentanil (18.2%) and Nalbuphine (14,3%) are provided as opioid analgesics. The non-opioid analgesics (NOA) including Ketamine/Esketamine (98,7%), Metamizole (88.3%), Paracetamol (66,2%), Ibuprofen (24,7%) and COX-2-inhibitors (7,8%) are most commonly available. The antispasmodic Butylscopolamine is available (81,8%) to most rescue stations. Fentanyl is the most commonly provided opioid analgesic for treatment of a traumatic pain (70.1%) and back pain (46.8%), Morphine for visceral colic-like (33.8%) and non-colic pain (53.2%). In cases of acute coronary syndrome is Morphine (85.7%) the leading analgesic substance. Among the non-opioid analgesics is Ketamine/Esketamine (90.9%) most frequently provided to treat traumatic pain, Metamizole for visceral colic-like (70.1%) and non-colic (68.6%) as well as back pain (41.6%). Butylscopolamine is the second most frequently provided medication after Metamizole for "visceral colic-like pain" (55.8%). EMS staff (with or without a request for presence of the EMS physician on site) are permitted to use the following: Morphine (16.9%), Piritramide (13.0%) and Nalbuphine (10.4%), and of NOAs for (Es)Ketamine (74.1%), Paracetamol (53.3%) and Metamizole (35.1%). The dosages of the most important and commonly provided analgesic substances permitted to independent treatment by the paramedics are often below the recommended range for adults (RDE). The majority of medical directors (78.4%) of the emergency services consider the independent application of analgesics by paramedics sensible. The reason for the relatively rare authorization of opioids for use by paramedics is mainly due to legal (in)certainty (53.2%). CONCLUSION: Effective analgesics are available for EMS staff in Germany, the approach to improvement lies in the area of application. For this purpose, the adaptations of the legal framework as well as the creation of a guideline for prehospital analgesia are useful.

Safety and Efficacy of Oral Nalbuphine on Postoperative Pain in Hemorrhoidectomy Patients: A Randomized, Double-blind, Placebo-controlled, Pivotal Trial.

OBJECTIVES: Severe postoperative pain requiring opioid treatment has been reported in 20% to 40% of hemorrhoidectomy patients. Compared with morphine, nalbuphine offers better hemodynamic stability, a lower risk of respiratory depression, and a lower potential for addiction. Nalbuphine was developed from the intravenous form into an oral form (PHN131) to alleviate moderate-to-severe pain. MATERIALS AND METHODS: A randomized, double-blind, placebo-controlled, multiple-dose, parallel-design trial was conducted to evaluate the safety and efficacy of PHN131 in patients undergoing hemorrhoidectomy. Eligible patients were randomly assigned to receive either PHN131 soft capsules containing nalbuphine hydrochloride 60 mg or placebo capsules. Intramuscular diclofenac was the rescue analgesic. Pain was measured by the area under the curve of mean Visual Analog Scale pain intensity scores. RESULTS: Visual Analog Scale results in patients receiving PHN131 were significantly lower than placebo group scores through 48 hours postoperatively (149.2±75.52 vs. 179.6±65.97; P =0.0301). According to Brief Pain Inventory Short-Form scores, the impact of pain on quality of life was significantly smaller for the PHN131 group than for the placebo group. Time to the first use of diclofenac postoperatively was significantly longer in the PHN131 group than in the placebo group. The cumulative dosage of diclofenac in the PHN131 group was only around half of that in the placebo group ( P <0.0001). Drug-related adverse events were mild-to-moderate and resolved by the treatment end. No drug-related severe adverse events were observed. DISCUSSION: Our findings demonstrate that PHN131 is effective and well-tolerated in the treatment of moderate-to-severe post hemorrhoidectomy pain and may provide another option for patients to control their pain.

The comparison of the analgesic efficacy of continuous paravertebral block alone compared with continuous paravertebral and intercostal nerve block for thoracotomy in adults: a randomized controlled trial.

PURPOSE: The study aims to compare the analgesic efficacy of two analgesic interventions, continuous paravertebral (PVB) nerve block alone with continuous paravertebral and intercostal nerve block (PVB/ICB) in patients undergoing thoracotomy. METHODS: A total of 70 patients undergoing thoracotomy were randomly enrolled in either continuous paravertebral nerve block (PVB) group or in continuous paravertebral and intercostal nerve block (PVB/ICB) group and received corresponding blocks. Analgesic efficacy measured by Visual Analog Scale (VAS) pain score, hemodynamic effects, total narcotic consumption, sedation score, patient's length of stay in hospital and patient's satisfaction with the analgesic technique were recorded. RESULTS: Demographic characteristics of the patients were similar in both groups. The mean VAS pain score was not statistically significant in both groups at 24 h. The mean pulse rate and blood pressures were comparable in both groups for the first 24 h. Nalbuphine consumption was significantly higher in PVB group as compared to PVB/ICB group at 1 h (p = 0.01), 6 h (p = 0.03) and 12 h (p = 0.009) and 24 h (p = 0.03). The mean total nalbuphine consumption in the PVB group was higher (28.29 mg vs. 22.63 mg) and statistically significant then PVB/ICB group (p = 0.03). The total tramadol consumption as a rescue analgesic was higher in the PVB group (131.42 mg) as compared to PVB/ICB group (120 mg) after 24 h but not statistically significant (p = 0.17). CONCLUSION: Continuous paravertebral nerve block with intercostal nerve block provides effective post-operative pain relief after thoracotomy with reduced narcotic consumption compared to continuous paravertebral nerve block alone. CLINICAL TRIAL REGISTRATION NUMBER: Clinicaltrails.gov NCT04715880.

Efficacy and safety of an extended-release sebacoyl dinalbuphine ester for laparoscopic cholecystectomy: A randomized controlled trial.

BACKGROUND: A long-acting κreceptor agonist parenteral analgesic may theoretically improve acute pain and reduce incidence of chronic postsurgical pain (CPSP) after laparoscopic cholecystectomy with minimal drug-related side effects of the traditional µreceptor opioids. METHODS: Eighty adult patients undergoing elective laparoscopic cholecystectomy were randomly assigned to receive single intramuscular injection of an extended-release sebacoyl dinalbuphine ester (SDE, Naldebain 150 mg; n = 40) or placebo (n = 40) after anesthesia induction. Standard multimodal analgesia (MMA) was administered for postoperative pain control. The primary endpoint was pain intensity within 7 days after surgery. The secondary endpoints were incidence CPSP at 3 months and adverse reactions up to 7 days after surgery. RESULTS: The highest visual analogue scale (VAS) and area under the curve of VAS 0 to 48 hours after operation were not different between the two groups and a similar proportion of patients requested rescue parenteral analgesics. Average pain intensities were also not different at 72 hours and 7 days after surgery. Incidence of CPSP was 22.5% and 13.1% in patients who received placebo and SDE treatment, respectively (P = .379). Significantly higher incidence of drug-related adverse events, including dizziness, nausea and injection site reactions, were recorded in the SDE group. CONCLUSION: A single dose of extended-release analgesic SDE given intraoperatively did not provide sufficient add-on effect for acute and chronic pain management after laparoscopic cholecystectomies in patients who received standard postoperative MMA. Intramuscular injection of 150 mg SDE in patients with average body mass causes adverse events that could have been overlooked. More clinical studies are warranted to determine the target populations who may benefit from SDE injections for improvement of acute and chronic postsurgical pain management.

Effect of nalbuphine plus ropivacaine on vaginal labor in epidural analgesia.

BACKGROUND: Various approaches using epidural analgesia have been employed for relieving labor pain and promoting spontaneous delivery. We aimed to evaluate the effect of nalbuphine and ropivacaine versus fentanyl and ropivacaine on the duration of delivery in parturients. METHODS: Clinical data of 160 full-term primiparous women who received either nalbuphine or fentanyl in combination with ropivacaine infusion for epidural labor analgesia in our hospital from December 2020 to May 2022 were retrospectively analyzed. The participants were divided into two groups based on anesthesia methods: nalbuphine group (NR group, n = 78) received 0.2 mg/mL nalbuphine combined with 0.1% ropivacaine hydrochloride for patient-controlled epidural analgesia (PCEA) and fentanyl group (FR group, n = 82) received 2 ug/mL fentanyl citrate and 0.1% ropivacaine hydrochloride for PCEA. Both groups received an epidural blockade for labor analgesia at lumbar 2-3 interspace. The duration of the first, second, and third stages of labor, the onset of analgesia, and time before delivery (T0), 15 min of analgesia (T1), 30 min of analgesia (T2), full opening of the uterine opening (T3),exerts force during childbirth(T4), heart rate (HR), blood pressure (BP), blood saturation (SpO2), visual analogue pain scale (VAS) score, Ramsay sedation score, and modified Bromage score, and 5 min were recorded at 2 h postpartum (T5). The neonatal Apgar score, neonatal behavioral neurological assessment (NBNA) score, maternal nausea, vomiting, and itchy skin were recorded. RESULTS: Compared with the FR group, the first stage of labor duration (p < 0.05) and total duration of labor (p < 0.05) were shortened and the onset of analgesia (p < 0.05) was increased in the NR group. NR group had lower incidence of urinary retention than FR group (p < 0.05). The maternal and neonatal investigational parameters and scores had no significant difference between the two groups. CONCLUSIONS: Nalbuphine combined with ropivacaine in epidural block labor has a faster onset of analgesia and has a lower incidence of urinary retention than fentanyl combined with ropivacaine, and nalbuphine shortens the duration of the first and total stages of labor. Both nalbuphine and fentanyl can reduce pain during labor, have little effect on maternal hemodynamics, and have no significant effect on neonatal Apgar or NBNA scores.

Comparative pharmacokinetics of nalbuphine nasal spray and solution for injection in healthy volunteers.

AIMS: Nalbuphine is a synthetic opioid with comparable analgesic activity to morphine but with a better safety profile. Nalbuphine is only available in injectable form due to low oral bioavailability. Nasal nalbuphine spray provides advantages in drug safety, avoids hepatic first-pass metabolism, is non-invasive and is convenient for patient-controlled analgesia by self-administration. This study aimed to evaluate the safety and pharmacokinetics (PK) of the newly developed nalbuphine nasal spray in comparison with a solution for injections. METHODS: Twenty-four healthy Caucasian volunteers were enrolled in this randomized, open-label, cross-over study. Subjects were administered one of the drugs: nasal spray 7.0 mg/dose, nalbuphine hydrochloride solution for injection 10 mg/dose intravenously (IV) or intramuscularly (IM). High-performance liquid chromatography-tandem mass spectrometry was used to determine nalbuphine concentrations. RESULTS: A comparison of PK profiles for IV, IM and intranasal (IN) routes of nalbuphine administration revealed a close similarity of absorption phases for nasal spray and IM injection. Differences between the mean Tmax and dose-adjusted Cmax values for nasal spray and IM injection were statistically insignificant. The median values of the elimination rate constants and the terminal elimination half-life following IV, IM and IN nalbuphine administration were similar. The mean absolute bioavailability of the nasal spray equalled 65.04%. CONCLUSIONS: The similarity of PK parameters of IM-injected nalbuphine solution and the nasal spray allows us to assume the latter is a feasible alternative to intramuscular nalbuphine injections appropriate for self-administration and field environments for managing moderate and severe pain of various aetiologies.

Immobilization of Raccoons (Procyon lotor) with Nalbuphine, Medetomidine, and Azaperone.

Chemical immobilization is widely used by wildlife and veterinary professionals for the safe handling of animals. A combination of nalbuphine (40 mg/mL), azaperone (10 mg/mL), and medetomidine (10 mg/mL), known as NAM, is a low-volume combination with field immobilization practicality and fewer regulations restricting its use in the US than some other drug combinations. We evaluated the safety and effectiveness of NAM as an immobilizing agent for raccoons (Procyon lotor). From May 2021 to February 2022, 16 adult raccoons were captured in cage traps and immobilized with 0.3 mL NAM intramuscularly (12 mg nalbuphine, 3 mg medetomidine, and 3 mg azaperone, regardless of body weight). After administration, time to sedation was measured; body temperature, heart rate, respiratory rate, and oxygen saturation were monitored and recorded every 5 min for 20 min. Each raccoon was weighed; the dose administered was calculated (range 2.2-4.1 mg/kg, mean 3 mg/kg). Mean induction time was 6 min (4-17 min); time to recovery following administration of 15 mg atipamezole, 7.5 mg naltrexone for reversal, was 10 min (6-18 min). Heart rate, oxygen saturation, and respiration rate remained steady during immobilization. Rectal temperature steadily declined. Overall, NAM appeared to be a practical option for raccoon immobilization, providing rapid induction and reversal as well as adequate sedation for short-term handling and minimally invasive sampling.

Nalbuphine May Be Superior to Sufentanil in Relieving Postcesarean Uterine Contraction Pain in Multiparas: A Retrospective Cohort Study.

Purpose: Postcesarean pain remains a major complaint from puerperium women who have undergone cesarean section, especially uterine contraction induced visceral pain. The optimal opioid for pain relief after cesarean section (CS) is still unclear. The goal of this study was to compare the analgesic effect of Nalbuphine to Sufentanil in patients who underwent CS. Patients and Methods: In this single-center retrospective cohort study, we included patients who received Nalbuphine or Sufentanil Patient-Controlled Intravenous Analgesia (PCIA) after CS between 1 January 2018 and 30 November 2020. Data on a Visual Analog Scale (VAS) at uterine contraction, at rest, and at movement, analgesic consumption, and side effects were collected. We performed logistic regression to identify predictors of severe uterine contraction pain. Results: A total of 674 patients were identified in the unmatched cohort, and 612 patients in the matched one. Compared to the Sufentanil group, lower VAS-contraction was recorded in the Nalbuphine group in both the unmatched and matched cohorts, the mean difference (MD) on POD1 was 0.35 (95% CI: 0.17 to 0.54, p<0.001) and 0.28 (95% CI: 0.08 to 0.47, p<0.001), respectively, and the MD of POD2 was 0.12 (95% CI: 0.03 to 0.40, P=0.019) and 0.12 (95% CI: 0.03 to 0.41, P=0.026), respectively. On POD1 but not POD2, VAS-movement was lower in the Nalbuphine group as compared to the Sufentanil group. No difference was found between VAS-rest on POD1 and POD2 in both unmatched and matched cohorts. Less analgesic consumption, and side effects were recorded in the Nalbuphine group. Logistic regression indicated that multipara and analgesic consumption were risk factors for severe uterine contraction pain. In subgroup analysis, VAS-contraction was meaningfully reduced in the Nalbuphine group compared with the Sufentanil group in multipara patients, but not primiparas. Conclusion: Compared to Sufentanil, Nalbuphine may provide better analgesia on uterine contraction pain. The superior analgesia may only exhibit in multiparas.

Ultrasound-Guided Techniques for Postoperative Analgesia in Patients Undergoing Laparoscopic Sleeve Gastrectomy: Erector Spinae Plane Block vs. Quadratus Lumborum Block.

BACKGROUND: Laparoscopic sleeve gastrectomy (LSG) is a common bariatric surgery. Regional anesthetic techniques decrease postoperative pain, narcotic analgesic requirements, and opioid-related adverse effects in patients scheduled for bariatric surgery. OBJECTIVES: The research team conducted this clinical trial to assess the effects of bilateral ultrasound (US)-guided erector spinae plane block (ESPB) on postoperative pain scores and postoperative analgesics consumption compared with bilateral US-guided quadratus lumborum block (QLB) in the first 24 hours following LSG. STUDY DESIGN: A randomized, double-blind, prospective, single-center study. SETTING: Ain-Shams University Hospitals. METHODS: Patients: One hundred twenty morbidly obese patients were scheduled for LSG. INTERVENTION: Were randomly assigned to 3 groups (40 each): bilateral US-guided ESPB, bilateral US-guided QLB, or control (C) group. MEASUREMENTS: The time to first rescue analgesia (ketorolac) was considered as a primary outcome. The time to perform the block, the duration of anesthesia, the time to first ambulation, the visual analog scale (VAS) at rest, VAS at movement, the total nalbuphine consumption (mg), the total requirements of rescue analgesia (ketorolac) over the first 24 hours after surgery and the study safety profile were considered as secondary outcomes. RESULTS: The time to perform the block and the duration of anesthesia were higher in the QLB group compared to other groups, with significant differences between ESPB and C groups (P < 0.001, P < 0.001, respectively). The ESPB and QLB groups were superior to the C group as regards the time to first rescue analgesia, the total dose of rescue analgesia, and the total nalbuphine consumption (P < 0.001, P < 0.001, P < 0.001, respectively). In the C group, VAS-R and VAS-M readings were higher in the first 18 hours after surgery (P < 0.001, P < 0.001, respectively). In the rest 6 hours of 24 hours after surgery, the QLB group had lower VAS-R and VAS-M readings than the C group (P < 0.001, P < 0.001, respectively). More patients in the C group had higher incidences of nausea and vomiting (P = 0.011, P = 0.002, respectively). In the C group, the time to first ambulation, the length of PACU stay, and the hospital stay were higher in comparison to the ESPB and QLB groups (P < 0.001, P < 0.001, P < 0.001, respectively). More patients in the ESPB and QLB groups were satisfied with postoperative pain management protocol (P < 0.001). LIMITATIONS: The lack of postoperative respiratory assessment (e.g., spirometry) precluded the identification of either ESPB or QLB effects on pulmonary functions in such patients. CONCLUSION: Bilateral ultrasound-guided erector spinae plane block and bilateral ultrasound-guided quadratus lumborum block provided adequate postoperative pain control and reduced postoperative analgesic requirements for morbidly obese patients scheduled for laparoscopic sleeve gastrectomy with priority to bilateral erector spinae plane block.