nalbuphine and Pruritus

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.

Topics: Analgesics, Opioid; Humans; Morphine; Nalbuphine; Nurse Anesthetists; Pain, Postoperative; Postoperative Nausea and Vomiting; Pruritus

Evaluate the efficacy of prophylactic nalbuphine in preventing neuraxial opioid-induced pruritus.. Systematic review and meta-analysis.. Following the PRISMA statement, PubMed, CINAHL, Cochrane and EMBASE were searched for eligible studies.. 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.. Prophylactic nalbuphine decreased the incidence and severity of pruritus without adverse effects on sedation and analgesic effect of opioids.

Topics: Analgesics, Opioid; Female; Humans; Incidence; Nalbuphine; Pain; Pregnancy; Pruritus; Randomized Controlled Trials as Topic

End-stage renal disease chronic itch is a frequent symptom that bothers patients with advanced stages of chronic kidney disease. The pathogenesis of the chronic itch symptom is complex and not yet fully understood and includes many metabolic, immunologic, and neurogenic factors. A significant burden of the disease results in decreased quality of life with sleep impairment, depressive symptoms, and increased mortality of affected individuals. No treatment of choice is available; topical therapy (emollients), phototherapy (UV-B), and systemic therapy (antiepileptics, opioid agonists, and antagonists) provide significant relief in varying percentages of patients.

Topics: Amines; Analgesics, Opioid; Anticonvulsants; Antipruritics; Chronic Disease; Cyclohexanecarboxylic Acids; Emollients; Gabapentin; gamma-Aminobutyric Acid; Humans; Kidney Failure, Chronic; Nalbuphine; Narcotic Antagonists; Pregabalin; Pruritus; Quality of Life; Renal Dialysis; Severity of Illness Index; Ultraviolet Therapy

Opioid-induced pruritus is a common side effect of opioid treatment in patients with acute pain associated with surgery or childbirth. There are several options available to treat opioid-induced pruritus, including nalbuphine. However, it is not known whether nalbuphine offers greater efficacy in treating pruritus without attenuation of analgesia and an increase in the incidence of adverse outcomes.. A systematic search of studies assessing treatment efficacy of nalbuphine was conducted through Medline, PubMed, Cochrane Library, CINAHL, and ProQuest databases. The primary outcome was reduction of pruritus, whereas the secondary outcomes included analgesia and adverse outcomes.. Ten studies that met all inclusion criteria were identified, 9 of which were randomized controlled trials and 1 case report. The incidence of pruritus was higher among patients receiving neuraxial opioids than those with the intravenous route. Nalbuphine provided greater efficacy in treating opioid-induced pruritus when compared with placebo, control, or other pharmacologic agents such as diphenhydramine, naloxone, and propofol. There was no attenuation of analgesia or increase in sedation with low-dose nalbuphine treatment—25% to 50% of the dose to treat pain, that is, 2.5 to 5 mg versus 10 mg intravenously. Further, nalbuphine was associated with reduction of nausea or vomiting, and reversal of respiratory depression.. Nalbuphine is superior in treating opioid-induced pruritus when compared with placebo, control, diphenhydramine, naloxone, or propofol in patients receiving neuraxial opioids for acute pain related to surgery or childbirth. Therefore, it is recommended that nalbuphine should be used as a first-line treatment of opioid-induced pruritus.

Topics: Acute Pain; Analgesics, Opioid; Humans; Nalbuphine; Pruritus; Randomized Controlled Trials as Topic

Treatment of prurigo nodularis (PN) is challenging and new treatment options are needed.. To evaluate the efficacy and safety of two oral doses of the kappa opioid agonist and mu opioid antagonist nalbuphine extended release (NAL-ER) tablets in a phase 2, multicentre, randomized, double-blind, placebo-controlled trial with an open-label, 50-week extension phase.. Subjects with moderate-to-severe PN were randomized to NAL-ER 81 mg (NAL-ER81) or 162 mg (NAL-ER162) tablets twice-daily or placebo for 8 weeks of stable dosing following a 2-week titration period. Subjects completing Week 10 with a Worst Itch Numerical Rating Scale (WI-NRS) score ≥5 at the time of rollover (or during the observation period) were eligible for open-label treatment.. Of 63 randomized subjects, 62 were treated and comprised the modified intent-to-treat population (MITT), 50 completed 10 weeks of treatment. In the MITT analysis, 8 subjects (44.4%) treated with NAL-ER162 (P = 0.32) and 6 (27.3%) treated with NAL-ER81 (P = 0.78) achieved ≥30% reduction from baseline in 7-day WI-NRS at Week 10 (primary efficacy endpoint) vs. 8 (36.4%) in the placebo group. Itch reduction was significant among 8/12 (66.7%) subjects completing Week 10 treated with NAL-ER162 vs. placebo (8/20, 40.0%; P = 0.03). Additionally, 6 subjects (33.3%) treated with NAL-ER162 and 3 (13.6%) treated with NAL-ER81 achieved ≥50% reduction from baseline in 7-day WI-NRS at Week 10 (coprimary endpoint). Extended open-label treatment was associated with further improvements in itch reduction and favourable changes in PN lesion activity as assessed by Prurigo Activity Score. Adverse events occurred predominantly during dose titration and were of mild-to-moderate severity. The safety profile did not change with extended open-label treatment.. In adult subjects with PN, oral treatment with NAL-ER 162 mg twice daily provided measurable anti-pruritic efficacy in subjects completing ≥10 weeks of treatment and was well tolerated (ClinicalTrials.gov: NCT02174419).

Topics: Adult; Double-Blind Method; Gastrointestinal Diseases; Humans; Nalbuphine; Prurigo; Pruritus; Treatment Outcome

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.. 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.. 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).. 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.

Topics: Adult; Analgesics, Opioid; Anesthesia, Obstetrical; Anesthesia, Spinal; Anesthetics, Local; Bupivacaine; Cesarean Section; Double-Blind Method; Drug Combinations; Elective Surgical Procedures; Female; Humans; Morphine; Nalbuphine; Postoperative Complications; Postoperative Nausea and Vomiting; Pregnancy; Prospective Studies; Pruritus; Young Adult

Pruritus is a distressing hallmark of the uremic condition, affecting approximately 60% of hemodialysis patients. Abnormal endogenous opioid ligand activity at μ and κ-opioid receptors has been postulated as a mechanism in uremic pruritus. Nalbuphine is a μ-opioid antagonist and κ-opioid agonist.. In this multicenter, randomized, double-blind, placebo-controlled trial, 373 hemodialysis patients with moderate or severe uremic pruritus were randomized in a 1: 1:1 ratio to nalbuphine extended-release tablets 120 mg (NAL 120), 60 mg (NAL 60), or placebo and treated for 8 weeks. Three hundred seventy-one were analyzed for efficacy. The primary endpoint was the change from baseline to treatment weeks 7 and 8 in itching intensity on a Numerical Rating Scale (NRS, 0 [no itching]; 10 [worst possible itching]) using an intent-to-treat approach. The aim was to evaluate the safety and antipruritic efficacy of NAL.. The mean duration of itching was 3.2 years. From a baseline NRS of 6.9 (1.5), the mean NRS declined by 3.5 (2.4) and by 2.8 (2.2) in NAL 120 mg and the placebo groups, respectively (p = 0.017). There was no evidence of tolerance. A trend for less sleep disruption due to itching (p = 0.062, NAL 120 vs. placebo) was also observed. There were no significant differences between NAL 60 vs. placebo. Serious adverse events occurred in 6.7, 12.7, and 15.4% in the NAL 120, NAL 60, and placebo groups respectively.. In this largest-to-date randomized controlled trial in uremic pruritus, NAL 120 durably and significantly reduced the itching intensity among hemodialysis patients.

Topics: Adult; Aged; Analgesics, Opioid; Double-Blind Method; Female; Humans; Male; Middle Aged; Nalbuphine; Pruritus; Severity of Illness Index; Uremia

Epidural morphine in patient-controlled analgesia regimens controls postoperative pain well but easily induces pruritus and other epidural morphine-related side effects. With 90 pregnant American Society of Anesthesiologists physical status II females scheduled for elective cesarean delivery, the present study was designed to evaluate the efficacy and safety profile of patient-controlled antipruritus (PCP) use of intravenous nalbuphine-based regimens for attenuation of postoperative pruritus and related side effects in combination with epidural morphine patient-controlled analgesia with regard to the quality of postoperative pain management. Patients were randomly assigned to two nalbuphine groups (5 μg/kg/hour, Group N5 or 10 μg/kg/hour, Group N10) and bolus dose of 1.6 μg/kg for PCP or the control (normal saline) group. Comparable visual analog scale scores for rest pain at each measured time interval among the three groups demonstrated that adequate pain relief was offered; however, the cumulative dose of nalbuphine administered to the patients in Group N10 attenuated the analgesic effect of epidural morphine in moving pain at POh24 only. Fewer episodes and milder severity of pruritus were observed in patients in Groups N5 and N10 at all postoperative time intervals. Epidural morphine provided good postoperative pain relief but with incommodious side effects. In addition, intravenous nalbuphine not only attenuated the incidence of pruritus but also decreased total morphine consumption. In conclusion, intravenous administration of low-dose nalbuphine (5 μg/kg/hour) for PCP maintained analgesia produced by epidural morphine and offered low pruritus incidence.

Topics: Adult; Analgesia, Epidural; Analgesia, Patient-Controlled; Cesarean Section; Demography; Dose-Response Relationship, Drug; Female; Humans; Injections, Intravenous; Morphine; Nalbuphine; Pain Measurement; Pain, Postoperative; Pregnancy; Pruritus; Young Adult

The aim of the present study was to test the efficacy of epidural nalbuphine 5 mg for prevention of morphine-induced pruritus.. Parturients, ASA I-II scheduled for elective cesarean section under epidural anesthesia were randomized into 3 groups: the placebo group, N-5 group, and N-10 group received 4 ml epidural solution containing morphine 4 mg plus either saline, nalbuphine 5 mg, and nalbuphine 10 mg respectively. Pain score at rest and on movement, incidence and severity of pruritus, sedation score, and pethidine consumption were recorded for 24 hours.. The 182 parturients were randomized into 60 in the placebo group, 61 in the N-5 group, and 61 in the N-10 group. The severity of pruritus was significantly lower at 3, 6, 9 and 12 h postpartum in the N-5 group and the N-10 group had a lower degree of pruritus at 3 and 6 h postpartum compared to placebo. The VAS pain scores at rest and on movement were significantly higher in the N-10 group at 3, 6, 9, 12 and 18 h postpartum compared to the placebo and significantly higher at 3 h, 6 h postpartum compared to the N-5 group (p < 0.05). Patient's satisfactions were high in all groups without any significant difference between groups.. Epidural nalbuphine 5 mg reduced severity of morphine induced pruritus for 12 h with statistically significant different advantages over epidural nalbuphine 10 mg without anti-analgesic effect. However the difference is too small to convey into clinical significant advantage.

Topics: Adult; Analgesia, Epidural; Analgesics, Opioid; Analysis of Variance; Cesarean Section; Female; Humans; Morphine; Nalbuphine; Narcotic Antagonists; Pain Measurement; Pregnancy; Pruritus; Time Factors

This investigation evaluated the efficacy of nalbuphine in treating postoperative opioid-induced pruritus (Pr) in pediatric patients.. After Ethics Board approval, the dual site, tertiary care teaching centre study recruited 212 subjects, age > or = seven years, who received opioid analgesia postoperatively. A modified, self-report colour analogue scale (CAS) scored pruritus intensity (PrI). Subjects who reported PrI score > or = 5/10 were randomized to treatment with nalbuphine 50 microg x kg(-1) iv (max 5 mg) or saline placebo. A pruritus intensity difference (PrID) > or = 50% was considered a positive outcome.. Of 260 subjects approached, 212 consented and 184 received opioids. Median age was 13 yr (range 7-19) and median weight was 51 kg (range 19.6-134.8 kg). Pruritus intensity > or = 5/10 occurred in 37 (20.1%) subjects. Intravenous morphine [patient-controlled analgesia (PCA)/continuous infusion] was associated with Pr in 68% of subjects over a wide dose range (9.4-63.2 mug.kg(-1).hr(-1)). Pruritus occurred in 36% of patients in the PCA group compared to continuous opioid infusion (27%) and epidural administration (27%). Pruritus intensity difference > or = 50% was achieved in 55.6% of nalbuphine and 57.9% of saline-treated subjects.. This preliminary report suggests that nalbuphine 50 microg x kg(-1) iv is not effective in treating postoperative opioid-induced pruritus in pediatric patients. The modified CAS score and PrID warrant further investigation.

Topics: Adolescent; Adult; Analgesics, Opioid; Child; Data Collection; Dose-Response Relationship, Drug; Double-Blind Method; Female; Humans; Injections, Intravenous; Male; Nalbuphine; Narcotic Antagonists; Prospective Studies; Pruritus

In this prospective, randomized, double-blinded study, we compared the prophylactic efficacy of nalbuphine and ondansetron for the prevention of intrathecal morphine-induced pruritus after cesarean delivery. Two-hundred-forty parturients were randomly allocated into four groups. The N-4 group, O-4 group, O-8 group, and placebo group received IV 4 mg of nalbuphine, 4 mg of ondansetron, 8 mg of ondansetron, and 4 mL of normal saline, respectively, immediately after the baby was delivered. In the postanesthesia care unit, we found that the severity of pruritus score in the four groups was significantly different (P < 0.001). The prophylactic success rate for pruritus of the N-4, O-4, O-8, and placebo groups was 20%, 13%, 12%, and 6%, respectively (P < 0.001). The pruritus score between N-4 and placebo and O-4 and placebo was significantly different (P < 0.001 and P = 0.006, respectively). Treatment for pruritus was requested by patients in 25%, 47%, 51%, and 72% of patients in the N-4, O-4, O-8, and placebo groups, respectively (P < 0.001). There were no differences among groups in nausea/vomiting score, pain score, sedation score, or shivering score at 4, 8, and 24 h after surgery. Nalbuphine and ondansetron are more effective than placebo for the prevention of intrathecal morphine-induced pruritus after cesarean delivery.. Nalbuphine and ondansetron are more effective than placebo for the prevention of intrathecal morphine-induced pruritus after cesarean delivery.

Topics: Adult; Analgesics, Opioid; Cesarean Section; Double-Blind Method; Female; Humans; Morphine; Nalbuphine; Narcotic Antagonists; Ondansetron; Pain, Postoperative; Postoperative Complications; Postoperative Nausea and Vomiting; Pregnancy; Pruritus; Serotonin Antagonists

Minidose lidocaine-fentanyl spinal anesthesia (SAB(MLF)) is a safe, effective, and efficient anesthetic for ambulatory surgery. Unfortunately, it has a frequent incidence of pruritus and a substantial incidence of nausea and vomiting. Nalbuphine is effective in treating or preventing pruritus after intrathecal or epidural morphine but may or may not have a beneficial effect on nausea and vomiting. Droperidol has demonstrated antiemetic efficacy with neuraxial opiates. In this study, we examined the prophylactic use of nalbuphine alone compared with nalbuphine with droperidol after SAB(MLF). One-hundred-twenty-four patients having outpatient knee arthroscopy under SAB(MLF) with 20 mg of lidocaine 0.5% and 20 micro g of fentanyl were randomized to receive IV at the end of surgery either 4 mg of nalbuphine (Group N) or droperidol 0.625 mg plus nalbuphine 4 mg (Group ND). The incidences of early (before discharge) and late onset nausea were, respectively, 18% versus 5% and 32% versus 13%. The postoperative incidences of pruritus were 61% versus 40%, whereas 19% of patients in Group N compared with 2% of patients in Group ND requested treatment for this. Group ND had lower pain scores and had a longer delay until first use of analgesic. There were no differences in average times to discharge. The only side effect of the medications was an increased drowsiness in Group ND. In conclusion, as prophylactic medication for use in conjunction with SAB(MLF), the addition of droperidol 0.625 mg to nalbuphine 4 mg was superior to nalbuphine alone. The combination provided for reduced postoperative nausea, pruritus, and pain-benefits that persisted after discharge home. The combination also avoided isolated cases of extreme delay in discharge.. Droperidol in combination with nalbuphine enhances analgesia and is more effective than nalbuphine alone in preventing pruritus, nausea, and vomiting after minidose lidocaine-fentanyl spinal anesthesia.

Topics: Adult; Aged; Ambulatory Surgical Procedures; Anesthesia, Spinal; Droperidol; Drug Therapy, Combination; Electrocardiography; Female; Fentanyl; Humans; Lidocaine; Male; Middle Aged; Nalbuphine; Postoperative Nausea and Vomiting; Pruritus

In this prospective, randomized, double-blinded study, we compared the efficacy of nalbuphine and propofol for treating intrathecal morphine-induced pruritus after cesarean delivery. One-hundred-eighty-one parturients who developed moderate to severe pruritus after the administration of intrathecal morphine were randomly allocated into two groups. One group received 3 mg IV nalbuphine (n = 91), and the other received 20 mg IV propofol (n = 90). The improvement of pruritus and other adverse effects was determined at 10 min after study drug administration. The treatment success rate was higher in the Nalbuphine group than in the Propofol group (83% vs 61%; P < 0.001). Among the successfully treated patients, recurrence rates of moderate to severe pruritus within 4 h were not significantly different (nalbuphine 9% versus propofol 7%; P = 0.76). Other side effects, such as decreased analgesia, increased nausea, vomiting, increased sedation, pain on injection, and dizziness, were not significantly different between groups. Sedation and pain on injection, which were the two most common side effects, were minor and clinically inconsequential.. Nalbuphine was superior to propofol for the treatment of intrathecal morphine-induced pruritus after cesarean delivery.

Topics: Adult; Analgesics, Opioid; Cesarean Section; Double-Blind Method; Female; Humans; Injections, Spinal; Morphine; Nalbuphine; Postoperative Complications; Pregnancy; Prospective Studies; Pruritus

To search for the optimal dosage of nalbuphine relief of intrathecal-morphine induced pruritus after caesarean section.. Ninety parturients who developed moderate to severe pruritus caused by intrathecal morphine after caesarean section were randomly allocated into 3 groups receiving 2, 3 and 4 mg of intravenous nalbuphine respectively. The improvement of pruritus and adverse effects of nalbuphine such as increasing pain scores, nausea, vomiting, sedation and respiratory depression were evaluated at 15 minutes after nalbuphine administration.. Percentage of successful treatment of pruritus with 2, 3 and 4 mg, nalbuphine were 86.7, 96.7 and 100, respectively (p = 0.12). There was no statistically significant difference in adverse effects. No evidence of respiratory depression was detected. However, there was significant increase in pain scores in group of 4 mg nalbuphine (p = 0.004).. Nalbuphine of 2 to 3 mg was considered to be adequate in treatment of intrathecal morphine induced pruritus after caesarean section without increasing pain scores or causing other side effects.

Topics: Adult; Anesthesia, Obstetrical; Antipruritics; Cesarean Section; Dose-Response Relationship, Drug; Double-Blind Method; Female; Humans; Morphine; Nalbuphine; Narcotic Antagonists; Postoperative Complications; Pregnancy; Prospective Studies; Pruritus; Treatment Outcome

To compare both the efficacy and cost of nalbuphine and diphenhydramine in the treatment of intrathecal morphine-induced pruritus following Caesarean section.. Eighty patients, undergoing elective Caesarean section under spinal anaesthesia, were randomized, in a prospective, double-blind trial, to receive either nalbuphine (Group NAL) or diphenhydramine (Group DIP) for the treatment of SAB morphine-induced pruritus. All patients received an intrathecal injection of 10-12 mg hyperbaric bupivacaine 0.75% and 200 micrograms preservative free morphine. Postoperative pruritus was assessed, using a visual analogue scale (VAS), for 24 hr. Pruritus treatment was administered upon patient request and by a nurse blinded to the treatment given. Patients who failed to respond to three doses of the study drug were deemed treatment failures. Patient satisfaction was assessed with a questionnaire given 24 to 48 hr after surgery. Direct drug costs were calculated based on the pharmacy provision costs as of April 1996.. Eighty patients were enrolled and 45 requested treatment for pruritus. Patients treated with NAL (n = 24) were more likely to achieve a VAS score of zero with treatment (83% vs 43%, P < 0.01), had a higher delta VAS following treatment (4 +/- 2 vs 2 +/- 2, P < 0.003), and experienced fewer treatment failures (4% vs 29%, P < 0.04), than those treated with DIP (n = 21). Group NAL patients were also more likely to rate their pruritus treatment as being good to excellent (96% vs 57%, P < 0.004). Direct drug costs were higher for NAL than for DIP ($6.4 +/- 3.1 vs $1.7 +/- 0.7, respectively, P < 0.0001).. Nalbuphine is more effective than diphenhydramine in relieving pruritus caused by intrathecal morphine and the cost differences are small.

Topics: Adult; Analgesics, Opioid; Antipruritics; Cesarean Section; Diphenhydramine; Double-Blind Method; Female; Humans; Injections, Spinal; Morphine; Nalbuphine; Patient Satisfaction; Postoperative Complications; Pregnancy; Prospective Studies; Pruritus

This randomized, double-blind study compared the efficacy of two mu-receptor antagonists, naloxone and nalbuphine, in the prophylactic management of pruritus in postcesarean section patients receiving epidural morphine. Dosages of study drugs were individualized by the use of a patient self-administration (PSA) device. All 51 patients were healthy women who received a uniform epidural anesthetic and epidural morphine (5 mg). Coded solutions were infused for 24 h, with 5-min PSA lockout times: Group A (n = 17), nalbuphine 2.5 mg/h, PSA nalbuphine 1 mg; Group B (n = 16), naloxone 50 micrograms/hr, PSA saline; Group C (n = 18), naloxone 50 micrograms/h, PSA naloxone 40 micrograms. Patients were assessed for pruritus and pain every 8 h for 24 h. Both naloxone and nalbuphine provided good relief for pruritus; median pain and pruritus scores were in the none-to-mild range (0-3) for all groups at all assessment intervals. The pruritus scores of the PSA saline group were higher during the 16- to 24-h period (P < 0.05) than the scores of either group receiving A-receptor antagonist by PSA. There was evidence of shortening of the duration of analgesia in patients receiving naloxone who required treatment for pruritus after 16 h. Patients who self-administered large doses of nalbuphine over the first 8 h also reported pain scores consistent with reversal of analgesia. The potency ratio for naloxone:nalbuphine for antagonism of the pruritic effects of epidural morphine was approximately 40:1. Intervention to treat either unrelieved pruritus or pain, respectively, was necessary in the following numbers of patients: Group A, 0/1; Group B, 1/1; Group C, 2/2. Prophylactic infusions offer the potential for labor cost savings by minimizing the need for episodic therapeutic interventions to treat pruritus.

Topics: Analgesia, Epidural; Analgesia, Obstetrical; Analgesia, Patient-Controlled; Analgesics, Opioid; Cesarean Section; Cost Savings; Double-Blind Method; Female; Humans; Linear Models; Morphine; Nalbuphine; Naloxone; Narcotic Antagonists; Pain Measurement; Pain, Postoperative; Pregnancy; Pruritus; Receptors, Opioid, mu

Topics: Analgesia, Epidural; Clinical Trials as Topic; Double-Blind Method; Fentanyl; Humans; Middle Aged; Morphinans; Nalbuphine; Pruritus; Random Allocation

The effect of nalbuphine on the respiratory depression, pruritus and analgesia induced by epidural morphine was determined in a randomized, prospective, double-blind, placebo-controlled fashion. Twenty ASA physical status I women received 0.1 mg.kg-1 epidural morphine at induction of general anaesthesia for elective total abdominal hysterectomy. Group 1 (n = 14) received 0.3 mg.kg-1 nalbuphine intravenously six hours after the epidural morphine administration. Group 2 (n = 6) received saline. Prior to agent administration, six patients from the nalbuphine group and four patients from the saline group had respiratory depression indicated by a PaCO2 greater than 45 mmHg. After nalbuphine administration the PaCO2 (mean +/- SE) decreased from 49.5 +/- 1.2 mmHg to 42.5 +/- 0.7 mmHg (p less than 0.005) while there was no significant change after saline administration. Nine of the 14 patients receiving nalbuphine appeared to become more sedated, despite an improvement in ventilation. Pruritus was antagonized by 0.1 mg.kg-1 nalbuphine (p less than 0.006). There was no reversal of analgesia after administration of 0.3 mg.kg-1 nalbuphine.

Topics: Adult; Analgesia, Epidural; Carbon Dioxide; Depression, Chemical; Double-Blind Method; Female; Humans; Hysterectomy; Morphinans; Morphine; Nalbuphine; Pain Measurement; Pain, Postoperative; Prospective Studies; Pruritus; Random Allocation; Respiration

Population pharmacokinetic (PK) and pharmacokinetic-pharmacodynamic (PK-PD) models were used to describe the exposure-response (E-R) relationship between nalbuphine exposure and two widely used rating scales for itch: the Numerical Rating Scale for the subject's 'average'; itch experience (NRS-AV) and the Worst Itch (WI-NRS), with 24-h recall. Simulations based on the model E-R relationship were used to support dose selection for Phase 3 clinical trials and were evaluated with a target of reducing the 7-day average of the 24-h WI-NRS by at least 30% from baseline in most of the analysis population.. Data from two clinical trials (NCT02373215: 9 healthy subjects; NCT02174419: 62 subjects with PN), in patients with prurigo nodularis (PN) with moderate to severe itch who received treatment with either of two doses of nalbuphine extended release (ER) or placebo, were used for the analysis. A two-compartment PK model with serial zero and first-order oral absorption was used to describe drug exposure. A maximum effect (. The PK-PD model predicted the exposure-related reduction in both NRS-AV and WI-NRS over time with approximately 63% and 27% of. Simulated dose response indicated that 108 and 162 mg BID doses result in the highest proportion of patients achieving at least a 30% reduction in NRS-AV and WI-NRS, respectively.

Topics: Humans; Nalbuphine; Prurigo; Pruritus

Antipruritic effects of kappa opioid receptor (KOR) agonists have been shown in rodent models of acute and chronic scratching (itchlike behavior). Three KOR agonists, nalfurafine, difelikefalin, and nalbuphine, are in clinical studies for antipruritic effects in chronic itch of systemic and skin diseases. Nalfurafine (in Japan) and difelikefalin (in the USA) were approved to be used in the treatment of chronic itch in hemodialysis patients. The FDA-approved nalbuphine has been used in clinic for over 40 years, and it is the only narcotic agonist that is not scheduled. We aimed to study (a) antiscratch activity of nalbuphine against TAT-HIV-1 protein (controls HIV transcription)-, deoxycholic acid (DCA, bile acid)-, and chloroquine (CQ)-induced scratching in a mouse model of acute itch; and (b) whether the effect of nalbuphine is produced via KORs. First, dose-responses were developed for pruritogens. Mice were pretreated with nalbuphine (0.3-10 mg/kg) and then a submaximal dose of pruritogens were administered and the number of scratching bouts was counted. To study if the antiscratch effect of nalbuphine is produced via KOR, we used KOR knock out mice and pharmacologic inhibition of KORs using nor-binaltorphimine, a KOR antagonist. For this aim, we used CQ as a pruritogen. We found that: (a) TAT-HIV-1 protein elicits scratching in a dose-dependent manner; (b) nalbuphine inhibits scratching induced by TAT-HIV-1, DCA, and CQ dose-dependently; and (c) nalbuphine inhibits scratching induced by CQ through KORs. In conclusion, nalbuphine inhibits scratching elicited by multiple pruritogens.

Topics: Animals; Antipruritics; Behavior, Animal; Chloroquine; Deoxycholic Acid; Disease Models, Animal; Dose-Response Relationship, Drug; Male; Mice; Nalbuphine; Naltrexone; Narcotic Antagonists; Pruritus; Receptors, Opioid, kappa; tat Gene Products, Human Immunodeficiency Virus

Sebacoyl dinalbuphine ester (SDE) is a nalbuphine (NA) prodrug capable of biotransformation in vivo and prolong the duration of NA, maximize its effect in pain and pruritus management. However, the large molecular weight, low skin penetration, and stability concerns of SDE make it difficult to be used in local skin delivery. Nanostructured lipid carrier (NLC) is a lipid-based nanoparticulate system that has the potential for formulating SDE in order to promote drug delivery through the skin. The aim of this study was to develop SDE-loaded NLC formulations (SDE-NLC) with good stability, sustained release characteristics, and sufficient antipruritic effect. SDE was successfully encapsulated into NLC and the formulation increased the stability of SDE, enhanced skin penetration through hair follicles, and sustained SDE release during pruritus management. We also demonstrated that topical application of SDE-NLCs significantly reduced the number of scratches in pruritus-induced mice. Both NA and SDE were found in the skin strata, but only NA was detectable in the plasma, indicating rapid conversion of SDE into NA. All results demonstrated that SDE-NLC formulation protected SDE from degradation in vitro, while the released prodrug was converted into NA in vivo and extended antipruritic effect. The formulation has the potential of improving the life quality of patients with chronic pruritus.

Topics: Animals; Drug Carriers; Humans; Lipids; Mice; Nalbuphine; Nanostructures; Particle Size; Pruritus

Chronic itch is one of the disturbing symptoms of inflammatory skin diseases. Kappa opioid receptor agonists are effective in suppressing scratching in mice against different pruritogens. Nalbuphine, a nonscheduled kappa opioid receptor agonist and mu opioid receptor antagonist, has been in clinical use for post-operative pain management since the 1980s and recently has been in clinical trials for chronic itch of prurigo nodularis (https://www.trevitherapeutics.com/nalbuphine). We studied whether nalbuphine is effective against chronic scratching induced by rostral neck application of 1-fluoro-2,4-dinitrobenzene (DNFB), an accepted mouse model of contact dermatitis to study pruritoceptive itch. Mice were treated once a week with either saline or nalbuphine 20 min before the third, fifth, seventh, and ninth sensitizations with DNFB and the number of scratching bouts was counted for 30 min. Skin samples from the neck of mice at week 4 were used to measure protein levels and mRNA expressions of chemokines and cytokines. Different sets of mice were used to study sedation and anhedonic-like behavior of nalbuphine. We found that: nalbuphine (a) antagonized scratching in a dose- and time-dependent manner without affecting locomotion, b) decreased IL-31, and increased anti-inflammatory IL-10, and c) induced more elevations in the levels of CCL2, CCL3, CCL12, CXCL1, CXCL2, CXCL9, CXCL10, IL-1β, IL-16, TIMP-1, M-CSF, TREM-1 and M1-type macrophages compared to saline. Increases in chemokines and cytokines and M1 macrophages by nalbuphine suggest an inflammatory phase of healing in damaged skin due to scratching. Our data indicate that nalbuphine is an effective antipruritic in murine model of pruritoceptive itch.

Topics: Animals; Chemokines; Dermatitis, Contact; Interleukin-10; Interleukins; Macrophages; Male; Mice; Monocytes; Nalbuphine; Pruritus; Receptors, Opioid, kappa; Receptors, Opioid, mu

Uremic pruritus is a common and deleterious condition among hemodialysis (HD) patients. Central gating of μ/κ opiate circuitry plays an important role in mediating and countering pruritogenic sensation. The objective of this study was to assess the safety and pharmacokinetics (PK) of the mixed μ-antagonist/κ-agonist nalbuphine, administered orally as nalbuphine HCl extended release (ER) tablets in HD patients, and explore its effect on pruritus.. In this open-label multiple escalating dose study, 15 HD patients with pruritus and 9 matched healthy subjects were enrolled. Nalbuphine HCl ER dose was escalated from 30 mg QD to 240 mg BID over 15 days. A full PK profile was obtained under dialysis and non-dialysis conditions as a function of dose. Clearance during dialysis was determined by sampling dialysate and arterial/venous blood during dialysis. Pruritus severity was assessed twice daily using a Visual Analog Scale (VAS). Safety monitoring included extensive monitoring of EKG, blood pressure, and pulse oximetry.. In HD patients, nalbuphine concentration peaked within 4-9 hours and attained steady state within 2-3 days, with no significant accumulation. Mean half-life was 14.2 hours, mean Cmax and AUCtau ranged between 13 and 83 ng/mL and 118 and 761 ng∙h/mL, respectively, with exposure increasing in a nearly dose-proportional fashion. Exposure in HD patients was about 2-fold higher than in healthy subjects. There was no meaningful difference between exposure on dialysis and non-dialysis days with 1% or less of the dose removed by dialysis. Nalbuphine suppressed itch in a dose-dependent manner, reducing mean VAS score from 4.0 to 1.2 at 180 mg and 0.4 at 240 mg.. Nalbuphine HCl ER tablets can be safely administered to HD patients without dose adjustment up to 240 mg BID and may hold promise in treating uremic pruritus.

Topics: Administration, Oral; Adult; Aged; Analysis of Variance; Area Under Curve; Case-Control Studies; Delayed-Action Preparations; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Humans; Kidney Failure, Chronic; Male; Middle Aged; Nalbuphine; Patient Safety; Pruritus; Reference Values; Renal Dialysis; Risk Assessment; Severity of Illness Index; Treatment Outcome; Visual Analog Scale

A case of nalbuphine-induced psychosis, which resolved after the administration of naloxone, is described.. A 25-year-old African-American woman with a history of systemic lupus erythematosus was admitted to the hospital for management of cholecystitis. A laparoscopic cholecystectomy was performed, and the patient received multiple doses of i.v. hydromorphone for postoperative pain management. Four days later, shortly after receiving a dose of i.v. nalbuphine for opioid-induced pruritus, she experienced an acute psychotic event, with symptoms including intense headache, akathisia, altered mental status, and formication (a hallucinatory sensation of insects crawling on the skin). The neuropsychiatric symptoms abated within 5 minutes of two consecutively administered doses of i.v. naloxone. During this event, which lasted 25-30 minutes, there was no evidence of metabolic abnormalities and were no signs of infection. The patient did not have a history of mental illness or substance abuse. The patient did not receive further doses of nalbuphine and did not experience similar events during her hospital stay; she was discharged home 10 days later without further complications. According to the algorithm of Naranjo et al., the case was assigned a score of 6, indicating a probable adverse reaction to nalbuphine.. A patient developed an acute psychotic reaction that was probably secondary to administration of i.v. nalbuphine for opioid-induced pruritus. Evidence supporting this diagnosis included correlation between the timing of administration of nalbuphine and symptom onset and the marked improvement in mentation following the administration of naloxone.

Topics: Adult; Analgesics, Opioid; Female; Humans; Nalbuphine; Naloxone; Narcotic Antagonists; Pruritus; Psychoses, Substance-Induced; Treatment Outcome

Intrathecal opioids have been shown to be safe and effective for postoperative analgesia in healthy children for spinal surgery. The aim of this study was to evaluate the applicability of intrathecal opioids in severely handicapped children scheduled for spinal surgery.. With hospital ethical committee approval, patients with physical states III and IV of the ASA classification requiring spinal surgery were retrospectively studied. In addition to inhalational anesthesia with sevoflurane or intravenous anesthesia using propofol, morphine 20 microg/kgBW and sufentanil 1.5 microg/kgBW were administered intrathecally before surgery. After surgery an infusion of nalbuphine was started. Need for additional intraoperative and postoperative analgesics, time of extubation, postoperative pain scores and p(a)CO2 values as well as adverse effects were recorded.. A total of 28 patients aged from 2.8 to 18.5 years (median 11.6 years) were studied. Immediate tracheal extubation in the operating room was possible in 17 patients and for 11 patients delayed extubation was elected. All patients were extubated within 24 h except for 1 patient who received massive postoperative transfusions. In 26 out of 28 patients (93%) the combination of intrathecal opioids with postoperative nalbuphine provided adequate analgesia. Observed side effects were post-operative nausea and vomiting (PONV), pruritus and moderate hypoventilation. In two patients a change to intravenous morphine therapy was necessary.. The use of intrathecal opioids for perioperative pain control from spinal fusion in severely handicapped children is feasible. Intrathecal opioids provide adequate postoperative analgesia and allow early extubation without persisting relevant respiratory compromise in most of these patients.

Topics: Adolescent; Analgesia; Analgesics, Opioid; Child; Child, Preschool; Disabled Children; Female; Humans; Injections, Spinal; Kaplan-Meier Estimate; Male; Nalbuphine; Pain; Pain Measurement; Pain, Postoperative; Perioperative Care; Postoperative Nausea and Vomiting; Pruritus; Retrospective Studies; Spine

Topics: Analgesics, Opioid; Antipruritics; Humans; Nalbuphine; Pruritus

Topics: Analgesics, Opioid; Antipruritics; Humans; Nalbuphine; Pain, Postoperative; Piperidines; Pruritus; Remifentanil

This is a retrospective study covering the ten-year period 1984-1993. Single shot spinal morphine (ITM) is compared with PCA nalbuphine for postoperative pain relief in children having abdominal or thoracic procedures. The records of 52 patients meeting selection criteria were examined. Nursing and physician notations were reviewed for hourly pain assessments, evidence of associated complications, respiratory depression, nausea and or vomiting, pruritus, and urinary retention. ITM provided significantly better pain relief (2.2 h in pain) during the first 24 h postoperatively than PCA nalbuphine (9.2 h in pain). With the exception of urinary retention which was significantly more frequent following ITM (58.6%) compared to PCA nalbuphine (8.7%), narcotic related complications were not different between the two groups. No difference in duration of hospital stay or ICU stay could be demonstrated. We conclude that ITM provides better pain relief, without more serious complications, than PCA nalbuphine. We recommend it as a safe, effective technique to treat postoperative pain in children following thoracic or upper abdominal procedures.

Topics: Abdomen; Adolescent; Analgesia, Patient-Controlled; Analgesics, Opioid; Child; Child, Preschool; Critical Care; Female; Hospitalization; Humans; Injections, Spinal; Length of Stay; Male; Morphine; Nalbuphine; Nausea; Pain Measurement; Pain, Postoperative; Pruritus; Respiration; Retrospective Studies; Thoracic Surgery; Urinary Retention; Vomiting

Topics: Adult; Analgesia; Anesthesia, Epidural; Cesarean Section; Female; Humans; Hydromorphone; Morphinans; Nalbuphine; Pruritus