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Does nalbuphine have a niche in managing pain?

Mellar P. Davis, MD, FCCP, FAAHPM, Carlos Fernandez, MD, Sally Regel, CRNP, Mary Lynn McPherson, PharmD, MA, MDE, BCPS, CPE


Nalbuphine has been commercially available for 40 years for the treatment of acute pain; few studies have centered on management of chronic pain. Nalbuphine unique pharmacology is an advantage in pain management. It is μ antagonist, partial κ agonist for G-proteins and beta-arrestin-2. Benefits are related to G-protein interactions resulting in less nausea, pruritus, and respiratory depression than morphine. At low doses, nalbuphine reduces side effects particularly respiratory depression without loss of analgesia when combined with potent opioids. Nalbuphine pharmacokinetics are moderately altered in renal failure. Several studies have found that nalbuphine reduces uremic pruritus. Nalbuphine has drawbacks: it is not an oral formulation, it causes withdrawal in patients on sustained released opioids, and it cannot be used to treat an opioid withdrawal syndrome. Nalbuphine, despite being a μ receptor antagonist produces a drug-liking effect and can be abused. There are very few deaths associated with nalbuphine alone in part due to the fact it is rarely used but also related to a ceiling on respiratory depression.


nalbuphine, opioid, pain, κ, μ, analgesia, pruritus

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Errick JK, Heel RC: Nalbuphine. A preliminary review of its pharmacological properties and therapeutic efficacy. Drugs. 1983; 26: 191-211.

Schmidt WK, Marynowski ME, Smith C: Nalbuphine, pentazocine, and butorphanol interactions with tripelennamine in mice. NIDA Res Monogr. 1986; 67: 145-146.

Schmidt WK, Tam SW, Shotzberger GS, et al.: Nalbuphine. Drug Alcohol Depend. 1985; 14: 339-362.

Beguin C, Potuzak J, Xu W, et al.: Differential signaling properties at the kappa opioid receptor of 12-epi-salvinorin A and its analogues. Bioorg Med Chem Lett. 2012; 22: 1023-1026.

Pick CG, Paul D, Pasternak GW: Nalbuphine, a mixed kappa 1 and kappa 3 analgesic in mice. J Pharmacol Exp Ther. 1992; 262: 1044-1050.

Zeng Z, Lu J, Shu C, et al.: A comparision of nalbuphine with morphine for analgesic effects and safety: Meta-analysis of randomized controlled trials. Sci Rep. 2015; 5: 10927.

Jannuzzi RG: Nalbuphine for treatment of opioid-induced pruritus: A systematic review of literature. Clin J Pain. 2016; 32: 87-93.

Hawi A, Alcorn H Jr, Berg J, et al.: Pharmacokinetics of nalbuphine hydrochloride extended release tablets in hemodialysis patients with exploratory effect on pruritus. BMC Nephrol. 2015; 16: 47.

Raehal KM, Lowery JJ, Bhamidipati CM, et al.: In vivo characterization of 6beta-naltrexol, an opioid ligand with less inverse agonist activity compared with naltrexone and naloxone in opioid-dependent mice. J Pharmacol Exp Ther. 2005; 313: 1150-1162.

DiFazio CA, Moscicki JC, Magruder MR: Anesthetic potency of nalbuphine and interaction with morphine in rats. Anesth Analg. 1981; 60: 629-633.

Lake CL, Duckworth EN, DiFazio CA, et al.: Cardiovascular effects of nalbuphine in patients with coronary or valvular heart disease. Anesthesiology. 1982; 57: 498-503.

Ramsay JG, Higgs BD, Wynands JE, et al.: Early extubation after high-dose fentanyl anaesthesia for aortocoronary bypass surgery: Reversal of respiratory depression with low-dose nalbuphine. Can Anaesth Soc J. 1985; 32: 597-606.

Moldenhauer CC, Roach GW, Finlayson DC, et al.: Nalbuphine antagonism of ventilatory depression following high-dose fentanyl anesthesia. Anesthesiology. 1985; 62: 647-650.

Hartree C: Caution with nalbuphine in patients on long-term opioids. Palliative Med. 2005; 19: 168.

Smith J, Guly H: Nalbuphine and slow release morphine. BMJ. 2004; 328: 1426.

Houlihan KP, Mitchell RG, Flapan AD, et al.: Excessive morphine requirements after pre-hospital nalbuphine analgesia. J Accid Emerg Med. 1999; 16(1): 29-31.

Robinson N, Burrows N: Excessive morphine requirements after pre-hospital nalbuphine analgesia. J Accid Emerg Med. 1999; 16(5): 392.

Stambaugh JE Jr: The management of the patient with chronic pain due to advanced malignancy. J Med. 1982; 13: 183-190.

Elliott HW, Navarro G, Nomof N: A double blind controlled study of the pharmacologic effects of nalbuphine (EN-2234A). J Med. 1970; 1: 74-89.

Jasinski DR, Mansky PA: Evaluation of nalbuphine for abuse potential. Clin Pharmacol Ther. 1972; 13: 78-90.

Ward SJ, Portoghese PS, Takemori AE: Pharmacological profiles of beta-funaltrexamine (beta-FNA) and beta-chlornaltrexamine (beta-CNA) on the mouse vas deferens preparation. Eur J Pharmacol. 1982; 80: 377-384.

DiMattio KM, Ehlert FJ, Liu-Chen LY: Intrinsic relative activities of kappa opioid agonists in activating Galpha proteins and internalizing receptor: Differences between human and mouse receptors. Eur J Pharmacol. 2015; 761: 235-244.

Marrone GF, Grinnell SG, Lu Z, et al.: Truncated mu opioid GPCR variant involvement in opioid-dependent and opioid- independent pain modulatory systems within the CNS. Proc Natl Acad Sci USA. 2016; 113: 3663-3668.

Grinnell SG, Majumdar S, Narayan A, et al.: Pharmacologic characterization in the rat of a potent analgesic lacking respiratory depression, IBNtxA. J Pharmacol Exp Ther. 2014; 350: 710-718.

Land BB, Bruchas MR, Schattauer S, et al.: Activation of the kappa opioid receptor in the dorsal raphe nucleus mediates the aversive effects of stress and reinstates drug seeking. Proc Natl Acad Sci USA. 2009; 106: 19168-19173.

Bruchas MR, Land BB, Aita M, et al.: Stress-induced p38 mitogen-activated protein kinase activation mediates kappaopioid-dependent dysphoria. J Neurosci. 2007; 27: 11614-11623.

Brust TF, Alongkronrusmee D, Soto-Velasquez M, et al.: Identification of a selective small-molecule inhibitor of type 1 adenylyl cyclase activity with analgesic properties. Sci Signal. 2017; 10(467): eaah5381.

Schattauer SS, Miyatake M, Shankar H, et al.: Ligand directed signaling differences between rodent and human kappa-opioid receptors. J Biol Chem. 2012; 287: 41595-41607.

Grinnell SG, Ansonoff M, Marrone GF, et al.: Mediation of buprenorphine analgesia by a combination of traditional and truncated mu opioid receptor splice variants. Synapse. 2016; 70: 395-407.

Majumdar S, Grinnell S, Le Rouzic V, et al.: Truncated G protein-coupled mu opioid receptor MOR-1 splice variants are targets for highly potent opioid analgesics lacking side effects. Proc Natl Acad Sci USA. 2011; 108: 19778-19783.

Lo MW, Schary WL, Whitney CC Jr: The disposition and bioavailability of intravenous and oral nalbuphine in healthy volunteers. J Clin Pharmacol. 1987; 27: 866-873.

Lo MW, Lee FH, Schary WL, et al.: The pharmacokinetics of intravenous, intramuscular, and subcutaneous nalbuphine in healthy subjects. Eur J Clin Pharmacol. 1987; 33: 297-301.

Lake CL, DiFazio CA, Duckworth EN, et al.: High-performance liquid chromatographic analysis of plasma levels of nalbuphine in cardiac surgical patients. J Chromatogr. 1982; 233: 410-416.

Liu KS, Hu OY, Ho ST, et al.: Antinociceptive effect of a novel long-acting nalbuphine preparation. Br J Anaesth. 2004; 92: 712-715.

Beaver WT, Feise GA, Robb D: Analgesic effect of intramuscular and oral nalbuphine in postoperative pain. Clin Pharmacol Ther. 1981; 29: 174-180.

Jaillon P, Gardin ME, Lecocq B, et al.: Pharmacokinetics of nalbuphine in infants, young healthy volunteers, and elderly patients. Clin Pharmacol Ther. 1989; 46: 226-233.

Bressolle F, Khier S, Rochette A, et al.: Population pharmacokinetics of nalbuphine after surgery in children. Br J Anaesth. 2011; 106: 558-565.

Wang HJ, Hsiong CH, Ho ST, et al.: Commonly used excipients modulate UDP-glucuronosyltransferase 2b7 activity to improve nalbuphine oral bioavailability in humans. Pharm Res. 2014; 31: 1676-1688.

Scheerans C, Heinig R, Mueck W: Proposal for defining the relevance of drug accumulation derived from single dose study data for modified release dosage forms. Biopharm Drug Dispos. 2015; 36: 93-103.

Tammisto T, Tigerstedt I: Comparison of the analgesic effects of intravenous nalbuphine and pentazocine in patients with postoperative pain. Acta Anaesthesiol Scand. 1977; 21: 390-394.

Kay B, Lindsay RG, Mason CJ, et al.: Oral nalbuphine for the treatment of pain after dental extractions. Br J Anaesth. 1988; 61: 313-317.

Kantor TG, Hopper M: Oral nalbuphine in postpartum pain. Clin Pharmacol Ther. 1984; 35: 46-49.

Beaver WT, Feise GA: A comparison of the analgesic effect of intramuscular nalbuphine and morphine in patients with postoperative pain. J Pharmacol Exp Ther. 1978; 204: 487-496.

Zacny JP, Conley K, Marks S: Comparing the subjective, psychomotor and physiological effects of intravenous nalbuphine and morphine in healthy volunteers. J Pharmacol Exp Ther. 1997; 280: 1159-1169.

Fee JP, Brady MM, Furness G, et al.: Analgesia after hip replacement surgery: Comparison of nalbuphine with morphine. Br J Anaesth. 1989; 63: 756-758.

Wandless JG: A comparison of nalbuphine with morphine for post-orchidopexy pain. Eur J Anaesthesiol. 1987; 4: 127-132.

Kururattapun SA, Prakanrattana U: Nalbuphine versus morphine for postoperative analgesia in critically ill patients. J Med Assoc Thai. 1986; 69: 210-215.

Gal TJ, DiFazio CA, Moscicki J: Analgesic and respiratory depressant activity of nalbuphine: A comparison with morphine. Anesthesiology. 1982; 57: 367-374.

Fournier R, Van Gessel E, Macksay M, et al.: Onset and offset of intrathecal morphine versus nalbuphine for postoperative pain relief after total hip replacement. Acta Anaesthesiol Scand. 2000; 44: 940-945.

Ho ST, Wang JJ, Liu HS, et al.: Comparison of PCA nalbuphine and morphine in Chinese gynecologic patients. Acta Anaesthesiol Sin. 1998; 36: 65-70.

Schmauss C, Doherty C, Yaksh TL: The analgetic effects of an intrathecally administered partial opiate agonist, nalbuphine hydrochloride. Eur J Pharmacol. 1982; 86: 1-7.

Dan U, Rabinovici Y, Barkai G, et al.: Intravenous pethidine and nalbuphine during labor: A prospective double-blind comparative study. Gynecol Obstet Invest. 1991; 32: 39-43.

Podlas J, Breland BD: Patient-controlled analgesia with nalbuphine during labor. Obstet Gynecol. 1987; 70: 202-204.

Frank M, McAteer EJ, Cattermole R, et al.: Nalbuphine for obstetric analgesia. A comparison of nalbuphine with pethidine for pain relief in labour when administered by patient-controlled analgesia (PCA). Anaesthesia. 1987; 42: 697-703.

Moyao-Garcia D, Hernandez-Palacios JC, Ramirez-Mora JC, et al.: A pilot study of nalbuphine versus tramadol administered through continuous intravenous infusion for postoperative pain control in children. Acta Biomed. 2009; 80: 124-130.

Siddiqui KM, Chohan U: Tramadol versus nalbuphine in total intravenous anaesthesia for dilatation and evacuation. J Pak Med Assoc. 2007; 57: 67-70.

van den Berg AA, Montoya-Pelaez LF, Halliday EM, et al.: Analgesia for adenotonsillectomy in children and young adults: A comparison of tramadol, pethidine and nalbuphine. Eur J Anaesthesiol. 1999; 16: 186-194.

Zsigmond EK, Winnie AP, Raza SM, et al.: Nalbuphine as an analgesic component in balanced anesthesia for cardiac surgery. Anesth Analg. 1987; 66: 1155-1164.

Akshat S, Ramachandran R, Rewari V, et al.: Morphine versus nalbuphine for open gynaecological surgery: A randomized controlled double blinded trial. Pain Res Treat. 2014; 2014: 727952.

Woods MP, Rayburn WF, McIntosh DG, et al.: Nalbuphine after major gynecologic surgery. Comparison of patient-controlled analgesia and intramuscular injections. J Reprod Med. 1991; 36: 647-650.

Humphreys HK, Fleming NW: Opioid-induced spasm of the sphincter of Oddi apparently reversed by nalbuphine. Anesth Analg. 1992; 74: 308-310.

Madacsy L, Bertalan V, Szepes A, et al.: Effect of nalbuphine on the motility of the sphincter of Oddi in patients with suspected sphincter of Oddi dysfunction. Gastrointest Endosc. 2003; 57: 319-323.

Lee G, Low RI, Amsterdam EA, et al.: Hemodynamic effects of morphine and nalbuphine in acute myocardial infarction. Clin Pharmacol Ther. 1981; 29: 576-581.

Shook JE, Pelton JT, Hruby VJ, et al.: Peptide opioid antagonist separates peripheral and central opioid antitransit effects. J Pharmacol Exp Ther. 1987; 243: 492-500.

Teter KA, Viellion G, Keating EM: Patient controlled analgesia and GI dysfunction. Orthop Nurs. 1990; 9: 51-56.

Parker RK, Holtmann B, White PF: Patient-controlled epidural analgesia: Interactions between nalbuphine and hydromorphone. Anesth Analg. 1997; 84: 757-763.

Malinovsky JM, Lepage JY, Karam G, et al.: Nalbuphine reverses urinary effects of epidural morphine: A case report. J Clin Anesth. 2002; 14: 535-538.

Qi J, Li H, Zhao TB, et al.: Inhibitory effect of endomorphin-2 binding to the mu-opioid receptor in the rat pre-botzinger complex on the breathing activity. Mol Neurobiol. 2017; 54: 461-469.

Mustapic S, Radocaj T, Sanchez A, et al.: Clinically relevant infusion rates of mu-opioid agonist remifentanil cause bradypnea in decerebrate dogs but not via direct effects in the pre-Botzinger complex region. J Neurophysiol. 2010; 103: 409-418.

Blaise GA, Nugent M, McMichan JC, et al.: Side effects of nalbuphine while reversing opioid-induced respiratory depression: Report of four cases. Can J Anaesth. 1990; 37: 794-797.

Baxter AD, Samson B: Nalbuphine reversal of respiratory depression after epidural sufentanil. Crit Care Med. 1990; 18: 1049.

Baxter AD, Samson B, Penning J, et al.: Prevention of epidural morphine-induced respiratory depression with intravenous nalbuphine infusion in post-thoracotomy patients. Can J Anaesth. 1989; 36: 503-509.

Cheng EY, May J: Nalbuphine reversal of respiratory depression after epidural sufentanil. Crit Care Med. 1989; 17: 378-379.

Latasch L, Teichmuller T, Dudziak R, et al.: Antagonisation of fentanyl-induced respiratory depression by nalbuphine. Acta Anaesthesiol Belg. 1989; 40: 35-40.

Penning JP, Samson B, Baxter AD: Reversal of epidural morphine-induced respiratory depression and pruritus with nalbuphine. Can J Anaesth. 1988; 35: 599-604.

Bailey PL, Clark NJ, Pace NL, et al.: Antagonism of postoperative opioid-induced respiratory depression: Nalbuphine versus naloxone. Anesth Analg. 1987; 66: 1109-1114.

Freye E, Azevedo L, Hartung E: Reversal of fentanyl related respiratory depression with nalbuphine. Effects on the CO2-response curve in man. Acta Anaesthesiol Belg. 1985; 36: 365-374.

Hammond JE: Reversal of opioid-associated late-onset respiratory depression by nalbuphine hydrochloride. Lancet. 1984; 2: 1208.

Latasch L, Probst S, Dudziak R: Reversal by nalbuphine of respiratory depression caused by fentanyl. Anesth Analg. 1984; 63: 814-816.

Romagnoli A, Keats AS: Ceiling effect for respiratory depression by nalbuphine. Clin Pharmacol Ther. 1980; 27: 478-485.

Yeh YC, Lin TF, Chang HC, et al.: Combination of low-dose nalbuphine and morphine in patient-controlled analgesia decreases incidence of opioid-related side effects. J Formos Med Assoc. 2009; 108: 548-553.

Pongraweewan O, Santawata U, Weerasarn L, et al.: Epidural nalbuphine for post cesarean epidural morphine induced pruritus. J Med Assoc Thai. 2009; 92: 782-786.

Charuluxananan S, Kyokong O, Somboonviboon W, et al.: Nalbuphine versus ondansetron for prevention of intrathecal morphine-induced pruritus after cesarean delivery. Anesth Analg. 2003; 96: 1789-1793.

Charuluxananan S, Kyokong O, Somboonviboon W, et al.: Nalbuphine versus propofol for treatment of intrathecal morphine-induced pruritus after cesarean delivery. Anesth Analg. 2001; 93: 162-165.

Culebras X, Gaggero G, Zatloukal J, et al.: Advantages of intrathecal nalbuphine, compared with intrathecal morphine, after cesarean delivery: An evaluation of postoperative analgesia and adverse effects. Anesth Analg. 2000; 91: 601-605.

Somrat C, Oranuch K, Ketchada U, et al.: Optimal dose of nalbuphine for treatment of intrathecal-morphine induced pruritus after caesarean section. J Obstet Gynaecol Res. 1999; 25: 209-213.

Wang JJ, Ho ST, Tzeng JI: Comparison of intravenous nalbuphine infusion versus naloxone in the prevention of epidural morphine-related side effects. Reg Anesth Pain Med. 1998; 23: 479-484.

Ramsay MA, Flanders D: Nalbuphine and pruritus. Anaesthesia. 1997; 52(10): 1023.

Elias M: Nalbuphine and pruritus. Anaesthesia. 1997; 52(6): 613.

Kendrick WD, Woods AM, Daly MY, et al.: Naloxone versus nalbuphine infusion for prophylaxis of epidural morphine-induced pruritus. Anesth Analg. 1996; 82: 641-647.

Cohen SE, Ratner EF, Kreitzman TR, et al.: Nalbuphine is better than naloxone for treatment of side effects after epidural morphine. Anesth Analg. 1992; 75: 747-752.

Lake CL, Duckworth EN, DiFazio CA, et al.: Cardiorespiratory effects of nalbuphine and morphine premedication in adult cardiac surgical patients. Acta Anaesthesiol Scand. 1984; 28: 305-309.

Nagasaka H, Yaksh TL: Effects of intrathecal mu, delta, and kappa agonists on thermally evoked cardiovascular and nociceptive reflexes in halothane-anesthetized rats. Anesth Analg. 1995; 80: 437-443.

Schaer H, Baasch K, Achtari R: [Nalbuphine after enflurane or fentanyl—Effect on circulation and respiration]. Anaesthesist. 1986; 35: 478-484.

Roth A, Keren G, Gluck A, et al.: Comparison of nalbuphine hydrochloride versus morphine sulfate for acute myocardial infarction with elevated pulmonary artery wedge pressure. Am J Cardiol. 1988; 62: 551-555.

Litovchenko VS, Blinov AV: [Arrest of the painful syndrome by moradol and nubain in patients with ischemic heart disease]. Anesteziol Reanimatol. 1996; (4): 30-31.

Kay B, Healy TE, Bolder PM: Blocking the circulatory responses to tracheal intubation. A comparison of fentanyl and nalbuphine. Anaesthesia. 1985; 40: 960-963.

Greenbaum RA, Kaye G, Mason PD: Experience with nalbuphine, a new opioid analgesic, in acute myocardial infarction. J R Soc Med. 1987; 80: 418-421.

Jamidar HA, Crooks SW, Adgey AA: Nalbuphine versus diamorphine early in the course of suspected myocardial infarction. Eur Heart J. 1987; 8: 597-602.

Trouton TG, Adgey AA: High dose nalbuphine in early acute myocardial infarction. Int J Cardiol. 1989; 23: 53-57.

Chambers JA, Guly HR: Prehospital intravenous nalbuphine administered by paramedics. Resuscitation. 1994; 27: 153-158.

Stene JK, Stofberg L, MacDonald G, et al.: Nalbuphine analgesia in the prehospital setting. Am J Emerg Med. 1988; 6: 634-639.

Nikoda VV, Lebedeva RN, Artamoshina MP, et al.: [Comparative evaluation of the use of nalbuphine and buprenorphine in prehospital care]. Anesteziol Reanimatol. 1998; (5): 23-28.

Galinski M, Ruscev M, Pommerie F, et al.: [National survey of emergency management of acute pain in prehospital setting]. Ann Fr Anesth Reanim. 2004; 23: 1149-1154.

Borland ML, Jacobs I, Rogers IR: Options in prehospital analgesia. Emerg Med. 2002; 14: 77-84.

Kubica-Cielinska A, Zielinska M: The use of nalbuphine in paediatric anaesthesia. Anaesthesiol Intensive Ther. 2015; 47: 252-256.

Schaffer J, Piepenbrock S, Kretz FJ, et al.: [Nalbuphine and tramadol for the control of postoperative pain in children]. Anaesthesist. 1986; 35: 408-413.

Lauby V, Mallaret M, Riviere I, et al.: [Precipitation of opioid withdrawal syndrome with nalbuphine in a morphine dependent cancer patient]. Therapie. 1994; 49: 143-144.

Lin CP, Hsu CH, Fu WM, et al.: Key opioid prescription concerns in cancer patients: A nationwide study. Acta Anaesthesiol Taiwan. 2016; 54: 51-56.

Nakatsuka N, Minogue SC, Lim Masc J, et al.: Intravenous nalbuphine 50 is ineffective for opioid-induced pruritus in pediatrics. Can J Anaesth. 2006; 53: 1103-1110.

Etches RC, Sandler AN, Lawson SL: A comparison of the analgesic and respiratory effects of epidural nalbuphine or morphine in postthoracotomy patients. Anesthesiology. 1991; 75: 9-14.

Galeotti C, Courtois E, Carbajal R: How French paediatric emergency departments manage painful vaso-occlusive episodes in sickle cell disease patients. Acta Paediatr. 2014; 103: e548-e554.

Buchanan ID, Woodward M, Reed GW: Opioid selection during sickle cell pain crisis and its impact on the development of acute chest syndrome. Pediatr Blood Cancer. 2005; 45: 716-724.

Woods GM, Parson PM, Strickland DK: Efficacy of nalbuphine as a parenteral analgesic for the treatment of painful episodes in children with sickle cell disease. J Assoc Acad Minor Phys. 1990; 1: 90-92.

Shannon HE, Holtzman SG: Morphine training dose: A determinant of stimulus generalization to narcotic antagonists in the rat. Psychopharmacology. 1979; 61: 239-244.

Steinfels GF, Young GA, Khazan N: Self-administration of nalbuphine, butorphanol and pentazocine by morphine post-addict rats. Pharmacol Biochem Behav. 1982; 16: 167-171.

Rosow CE: The clinical usefulness of agonist-antagonist analgesics in acute pain. Drug Alcohol Depend. 1987; 20: 329-337.

Larance B, Ambekar A, Azim T, et al.: The availability, diversion and injection of pharmaceutical opioids in South Asia. Drug Alcohol Rev. 2011; 30: 246-254.

Wines JD Jr, Gruber AJ, Pope HG Jr: Nalbuphine hydrochloride dependence in anabolic steroid users. Am J Addict. 1999; 8: 161-164.

McBride AJ, Williamson K, Petersen T: Three cases of nalbuphine hydrochloride dependence associated with anabolic steroid use. Br J Sports Med. 1996; 30: 69-70.

Drug Informer website. Available at Accessed February 17, 2017.

Drug Enforcement Administration, Office of Diversion Control, Drug and Chemical Evaluation Section: Nalbuphine hydrochloride (Trade name: Nubain®). Available at Accessed 7 March, 2017.

Gear RW, Gordon NC, Hossaini-Zadeh M, et al.: A subanalgesic dose of morphine eliminates nalbuphine anti-analgesia in postoperative pain. J Pain, 2008; 9: 337-341.

Gear RW, Lee JS, Miaskowski C, et al.: Neuroleptics antagonize nalbuphine antianalgesia. J Pain. 2006; 7: 187-191.

Gear RW, Gordon NC, Miaskowski C, et al.: Dose ratio is important in maximizing naloxone enhancement of nalbuphine analgesia in humans. Neurosci Lett. 2003; 351: 5-8.

Gear RW, Gordon NC, Miaskowski C, et al.: Sexual dimorphism in very low dose nalbuphine postoperative analgesia. Neurosci Lett. 2003; 339: 1-4.

Gear RW, Miaskowski C, Gordon NC, et al.: The kappa opioid nalbuphine produces gender- and dose-dependent analgesia and antianalgesia in patients with postoperative pain. Pain. 1999; 83: 339-345.

Kshirsagar S, Gear R, Levine J, et al.: A mechanistic model for the sex-specific response to nalbuphine and naloxone in postoperative pain. J Pharmacokinet Pharmacodyn. 2008; 35: 69-83.

Gear R, Becerra L, Upadhyay J, et al.: Pain facilitation brain regions activated by nalbuphine are revealed by pharmacological fMRI. PloS One. 2013; 8: e50169.

Minai FN, Khan FA: A comparison of morphine and nalbuphine for intraoperative and postoperative analgesia. J Pak Med Assoc. 2003; 53: 391-396.

Miller RR: Evaluation of nalbuphine hydrochloride. Am J Hosp Pharm. 1980; 37: 942-949.

Lejus C, Blanloeil Y, Francois T, et al.: Post-operative intravenous continuous analgesia: Comparison of buprenorphine, fentanyl and nalbuphine. Eur J Anaesthesiol. 1996; 13: 57-65.

Lehmann KA, Tenbuhs B: Patient-controlled analgesia with nalbuphine, a new narcotic agonist-antagonist, for the treatment of postoperative pain. Eur J Clin Pharmacol. 1986; 31: 267-276.

Kay B, Krishnan A: On-demand nalbuphine for post-operative pain relief. Acta Anaesthesiol Belg. 1986; 37: 33-37.

Schnabel A, Reichl SU, Zahn PK, et al.: Nalbuphine for postoperative pain treatment in children. Cochrane Database Syst Rev. 2014; (7): CD009583.

Pugh GC, Drummond GB: A dose-response study with nalbuphine hydrochloride for pain in patients after upper abdominal surgery. Br J Anaesth. 1987; 59: 1356-1363.

Kay B: Patient-controlled analgesia. Can Anaesth Soc J. 1984; 31: 120-122.

Woollard M, Whitfield R, Smith K, et al.: Less IS less: A randomised controlled trial comparing cautious and rapid nalbuphine dosing regimens. Emerg Med J. 2004; 21: 362-364.

Woollard M, Jones T, Pitt K, et al.: Hitting them where it hurts? Low dose nalbuphine therapy. Emerg Med J. 2002; 19: 565-570.

Jones AG: Pre-hospital nalbuphine analgesia. J Accid Emerg Med. 1999; 16: 462.

Hyland-McGuire P, Guly HR: Effects on patient care of introducing prehospital intravenous nalbuphine hydrochloride. J Accid Emerg Med. 1998; 15: 99-101.

Gray A, Johnson G, Goodacre S: Paramedic use of nalbuphine in major injury. Eur J Emerg Med. 1997; 4: 136-139.

Johnson GS, Guly HR: The effect of pre-hospital administration of intravenous nalbuphine on on-scene times. J Accid Emerg Med. 1995; 12: 20-22.

Guly HR: Early management of myocardial infarction. Paramedics should give an opiate. BMJ. 1994; 308: 1159.

Klepper ID, Rosen M, Vickers MD, et al.: Respiratory function following nalbuphine and morphine in anaesthetized man. Br J Anaesth. 1986; 58: 625-629.

Schumann R: Anaesthesia for bariatric surgery. Best Pract Res Clin Anaesthesiol. 2011; 25: 83-93.

Schug SA, Raymann A: Postoperative pain management of the obese patient. Best Pract Res Clin Anaesthesiol. 2011; 25: 73-81.

Lee CW, Kelly JJ, Wassef WY: Complications of bariatric surgery. Curr Opinion Gastroenterol. 2007; 23: 636-643.



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