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.

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.

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.

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.

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.

Use of Nalbuphine for Treatment of Neuraxial Opioid-Induced Pruritus: A Systematic Review and Meta-Analysis.

Opioid-induced pruritus is prevalent after neuraxial administration of opioid. A number of preventive measures have been reported; however, only a few studies evaluated treatment strategies for established pruritus. The pharmacokinetics and pharmacodynamic profiles of nalbuphine make this drug ideal for the treatment of established pruritus. The primary outcome of this systematic review and meta-analysis was the incidence of pruritus after neuraxial opioid administration. Secondary outcomes were the incidence of sedation and postoperative nausea and vomiting. Pooled estimates were reported by calculating the risk ratio (RR) with 95% confidence interval (CI). Five trials consisting of 494 patients were included for analysis. There was a low quality of evidence that nalbuphine was effective in reducing the incidence of pruritus compared with active control (RR, 0.59; 95% CI, 0.38 to 0.93; P = .02). Conversely, there was no difference between the incidence of sedation (RR, 1.06; 95% CI, 0.42 to 2.71; P = .90) and postoperative nausea and vomiting (RR, 1.58, 95% CI, 0.75 to 3.31; P = .23). Although large studies are needed to decrease heterogeneity across studies, the current review showed that nalbuphine appears to reduce the incidence of opioid-induced pruritus.

Effect of three doses of nalbuphine on reversal of sedation and cardiopulmonary effects of morphine-acepromazine in healthy dogs.

OBJECTIVE: To evaluate the efficacy of three doses of nalbuphine in reversing sedative and cardiopulmonary effects of morphine-acepromazine in dogs. STUDY DESIGN: Prospective, randomized experimental trial. ANIMALS: A group of eight healthy Beagle dogs, aged 5-6 years and weighing 12.5 ± 2.1 kg. METHODS: Dogs were administered morphine (0.5 mg kg-1) and acepromazine (0.05 mg kg-1) intravenously (IV). After 20 minutes, dogs were administered one of four treatments IV: saline (control); or nalbuphine (0.3 mg kg-1; treatment N0.3), (0.6 mg kg-1; treatment N0.6) or (1.0 mg kg-1; treatment N1.0), in random order separated by 1 week. Sedation was scored using a numeric descriptive scale (NDS) and simple numerical scale (SNS). Heart rate, systolic arterial pressure (SAP), respiratory rate (fR) and rectal temperature (RT) were recorded before (BL), 20 minutes after morphine-acepromazine (T0), then 10 (T10), 30, 60 and 90 minutes after saline or nalbuphine. Arterial blood gases were measured at BL, T0 and T10. Values were compared with BL, T0 and among treatments using anova (p < 0.05) and the Bonferroni correction (p < 0.008). RESULTS: NDS for N0.6 and SNS for N0.6 and N1.0 at T30, and both scores for all nalbuphine treatments at T60-T90 were lower compared with T0 (p < 0.05). Sedation scores were not different among nalbuphine treatments. SNS scores were lower than control at T10 for N0.3 and N0.6 (p < 0.05). SAP and fR were lower than BL for all treatments at some time points (p < 0.05). RT was higher than control at T60 in the nalbuphine treatments (p < 0.001). PaO2 was lower in N0.3 at T0 compared with BL (p = 0.036). CONCLUSIONS AND CLINICAL RELEVANCE: All nalbuphine doses decreased the degree of sedation, without differences among them. Administration of nalbuphine resulted in minimal changes in measured cardiopulmonary variables.

The effects of lidocaine-prilocaine cream on responses to intravenous catheter placement in cats sedated with dexmedetomidine and either methadone or nalbuphine.

OBJECTIVE: To compare the reaction to cephalic intravenous (IV) catheter placement with or without lidocaine-prilocaine cream in cats sedated with dexmedetomidine and methadone or nalbuphine. STUDY DESIGN: Prospective, randomized, blind study. ANIMALS: A group of 24 female mixed breed cats. METHODS: Cats were randomly allocated to one of the two sedation protocols: dexmedetomidine (0.01 mg kg-1) and methadone (0.3 mg kg-1; DEXMET) or dexmedetomidine (0.01 mg kg-1) and nalbuphine (0.3 mg kg-1; DEXNALB). Sedation was scored 30 minutes later using a visual analog scale. Subsequently, a 2 × 3.5 cm area of the antebrachium over the cephalic vein was clipped, and half the cats within each protocol were randomly assigned for topical lidocaine-prilocaine cream (treatment), whereas no cream was applied to other cats (control). After 20 minutes, an attempt was made to place a 24 gauge catheter into the cephalic vein and the reaction of the cats to this procedure was scored using a numeric scale 0-3. Sedation and catheterization reaction scores were compared between sedation protocols and whether cats were administered lidocaine-prilocaine cream or not using the Friedman test followed by the Bonferroni procedure. A p value < 0.05 was considered significant. RESULTS: Sedation scores were not different between sedation protocols or between treatment and control cats within each protocol. All cats administered lidocaine-prilocaine cream showed no reaction to IV catheter placement. Among the control cats, no response was observed in one cat in DEXNALB. Catheterization reaction score was lower in the treatment cats in both the sedation protocols when compared with their respective controls. CONCLUSIONS AND CLINICAL RELEVANCE: Lidocaine-prilocaine cream applied for 20 minutes abolished the reaction to catheterization in cats sedated with dexmedetomidine and nalbuphine or methadone. Facilitation of IV catheter placement occurred within 20 minutes of lidocaine-prilocaine application.

Nalbuphine Reduces Opioid-Associated Urinary Retention in Pediatric Patients.

OBJECTIVES: To evaluate the effect of nalbuphine administration on urine output in critically ill children with opioid-associated urinary retention. DESIGN: Institutional review board approved, single center, retrospective medical chart review. SETTING: Large medical-surgical PICU within a free-standing, tertiary care children's hospital. PATIENTS: Patients admitted to the PICU between October 1, 2014, and February 29, 2016, who received IV nalbuphine after meeting criteria for opioid-associated oliguria (defined as urine output below 1 mL/kg/hr and received at least one dose of opioid therapy within the preceding 12 hr). INTERVENTIONS: None. MEASUREMENT AND MAIN RESULTS: Seventeen patients who received 21 doses of nalbuphine were analyzed. The median age and weight of patients were 6 years (interquartile range, 3-11.5 yr) and 18 kg (interquartile range, 12-35 kg), respectively. Two distinct dosing strategies became evident, specifically 0.05 mg/kg (n = 11 doses) and 0.1 mg/kg (n = 10 doses). Urine output increased significantly from baseline (median, 0 mL/kg/hr; interquartile range, 0-0.53 mL/kg/hr) to 6 hours post nalbuphine administration (median, 1.48 mL/kg/hr; interquartile range, 0-2 mL/kg/hr; p = 0.0002). Patients who received 0.1 mg/kg/dose had a greater urine output response compared with those who received 0.05 mg/kg/dose. Five patients (29%) had a catheter inserted into their bladder after administration of nalbuphine. Pain scores (grouped 6 hr before and after nalbuphine administration and single pain scores documented immediately before and after nalbuphine administration) were unchanged. CONCLUSIONS: Nalbuphine administration, at a dose of 0.1 mg/kg, improved urine output in a cohort of children with opioid-associated urinary retention. Pain control did not appear influenced by the provision of nalbuphine. Additional studies are needed to determine the influence of nalbuphine on urinary catheter insertion rates and catheter-associated urinary tract infections.

Postsurgery analgesic and sedative drug use in a French neonatal intensive care unit: A single-center retrospective cohort study.

OBJECTIVE: To describe pain assessment, the pattern of analgesic and sedative drug use, and adverse drug reactions in a neonatal intensive care unit (NICU) during the postsurgery phase. METHOD: Demographic characteristics, pain scores, and drug use were extracted and analyzed from electronic patient medical files for infants after surgery, admitted consecutively between January 2012 and June 2013. RESULT: One hundred and sixty-eight infants were included. Acute (DAN score) and prolonged (EDIN score) pain assessment scores were used in 79% and 64% of infants, respectively, on the 1st day. This percentage decreased over the 7 days following surgery. The weekly average scores postsurgery were 2/15 (±2.2) for the EDIN score and 1.6/10 (±2.0) for the DAN score. The rates of pain control were 88% for the EDIN and 72% for the DAN. The most prescribed opiate drug was fentanyl (98 patients; 58%) with an average dose of 1.8 (±0.6) µg/kg/h. Midazolam was used in 95 patients (56%), with an average dose of 35 (±14) µg/kg/h. A bolus was administered in 7% (±7.4) of the total dose for fentanyl and 8% (±9.3) for midazolam. Similar doses were used in term and preterm neonates. Of 118 patients receiving fentanyl and/or midazolam, 40% presented urinary retention, 28% a weaning syndrome. Paracetamol (155 patients; 92%) and nalbuphine (55 patients; 33%) were the other medications most often prescribed. CONCLUSION: The off-label use of fentanyl and midazolam was necessary to treat pain after surgery. Pain assessment should be conducted for all neonates in order to optimize their treatment. Research on analgesic and sedative medicine in vulnerable neonates seems necessary to standardize practices and reduce adverse drug reactions.

Immobilization of American Beaver (Castor canadensis) with Nalbuphine, Medetomidine, and Azaperone.

Thirty-two American beavers (Castor canadensis) were immobilized with a mixture of nalbuphine, medetomidine, and azaperone (NalMedA) for tail transmitter placement and health assessments prior to translocation. Inductions and reversals were very smooth, but regardless of the dose administered, which ranged from 0.02 to 0.06 mL/kg, many beavers reacted to mild stimuli such as being lifted out of the cage, drawing blood from the tail, expressing anal glands for sex determination, and turning on isoflurane to deepen anesthesia before placement of tail transmitters. On a scale from 1 to 5, a sedation score of 4 was achieved in 8/32 beavers and a sedation score of 5 in 1/32 of beavers given a mean (SD) dosage of 0.04 (0.01) mL/kg NalMedA, which equated to a mean of 1.09 (0.21) mg/kg nalbuphine, 0.43 (0.09) mg/kg medetomidine, and 0.36 (0.07) mg/kg azaperone. All other animals achieved lower sedation scores. Supplementary isoflurane was needed to deepen anesthesia before tail transmitter placement. Although Nal-MedA appeared to be safe for use in American beavers, the level of sedation achieved was quite variable. Supplementary oxygen is recommended to reduce hypoxemia.

Prophylactic Nalbuphine to Prevent Neuraxial Opioid-Induced Pruritus: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

PURPOSE: Evaluate the efficacy of prophylactic nalbuphine in preventing neuraxial opioid-induced pruritus. DESIGN: Systematic review and meta-analysis. METHODS: Following the PRISMA statement, PubMed, CINAHL, Cochrane and EMBASE were searched for eligible studies. FINDINGS: A total of 17 trials consisting of 1,052 patients were evaluated. Compared to placebo, there is low quality of evidence that nalbuphine was effective in reducing the incidence of pruritus in all patient population (RR, 0.66; 95% CI, 0.52 to 0.83; P = .0004) and obstetrics (RR, 0.81; 95% CI, 0.67 to 0.98; P = .03). We also found moderate quality of evidence that nalbuphine lowered pruritus in non-obstetrics, the number of rescue pruritus therapy and severity of pruritus episodes. However, nalbuphine did not cause sedation and affect pain scores. CONCLUSIONS: Prophylactic nalbuphine decreased the incidence and severity of pruritus without adverse effects on sedation and analgesic effect of opioids.

Effect of adding nalbuphine to intrathecal bupivacaine with morphine on postoperative nausea and vomiting and pruritus after elective cesarean delivery: a randomized double blinded study.

BACKGROUND: The use of intrathecal morphine may result in serious side effects in parturients undergoing cesarean delivery. Nalbuphine, is a mu receptor antagonist and a ĸappa receptor agonist. Combinations of opioid agonist and agonist antagonist can decrease the incidence of opioid related side effects. We aimed to investigate the effect of adding nalbuphine, to intrathecal morphine on postoperative nausea and vomiting and pruritus after a cesarean delivery. METHODS: Eighty parturient undergoing elective cesarean delivery under spinal anesthesia were randomized into two similar groups. Group 1: received 10 mg of 0.5% hyperbaric bupivacaine with 0.2 mg morphine. Group 2: received as a group 1 plus 0.5 mg nalbuphine, with total volume 2.5 mL in both groups. Measurements: Data on the severity of nausea and vomiting were collected using a numerical rating scale and visual analogue scale was used to quantify pruritus. Onset and duration of sensory blockade, Visual Analog Scale for pain, the first time to ask for rescue analgesia and total rescue analgesic consumption were recorded. RESULTS: Nausea and vomiting and pruritus severity scores and number of patients developed nausea and vomiting and pruritus were significantly lower (P<0.001) in group 2. Onset and duration of sensory block, time to first request for rescue analgesia, Visual Analog Scale for pain and paracetamol consumption showed no statistically differences between both groups (P>0.05). CONCLUSIONS: We concluded that the addition of nalbuphine to intrathecal bupivacaine plus morphine significantly reduced the incidence and severity of postoperative nausea and vomiting and pruritus without affecting analgesic potency.