• The Korean Journal of Pain
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• v.11 no.2
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• pp.247-252
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• 1998

Background: Tonsillectomy is one of the most common operation in children. Postoperative pain and its sequelae are universal complaints of the patients. The purpose of this study was to evaluate the effects of nalbuphine on the posttonsillectomy pain in children. Methods: Fifty-four pediatric patients undergoing tonsillectomy under general anesthesia were randomly allocated to one of the 3 groups 1) control group who received no analgesics, 2) received IV nalbuphine before induction of anesthesia and 3) received IV nalbuphine after both tonsillectomy. In postanesthetic recovery room, comfort level in all patients was assessed using the objective pain scale (OPS). Systolic blood pressure, diastolic blood pressure and heart rate were measured at just before and immediately after extubation and postanesthetic recovery room. Results: The pain scale score in group 2 was significantly lower than group 1, but no significantly different with group 3. There were no significant differences in blood pressure among three groups. The heart rate in group 2 and 3 was significantly lower than group 1 only at immediately after arriving recovery room. Conclusions: Administration of nalbuphine before induction is more effective on postoperative pain control after tonsillectomy in children.

• Journal of Ginseng Research
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• v.29 no.2
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• pp.86-93
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• 2005

This study was undertaken to determine the antagonism of the ginseng total saponin (GTS) on the development of nalbuphine-induced tolerance and physical dependence. GTS is blown to have antinarcotic action with a dose of 100mg/kg (i.p.) in rats. STS significantly inhibits the development of nalbuphine-induced physical dependence as well as the tolerance. The level of pCREB was elevated in the striatum by the chronic treatment with nalbuphine or GTS, how-ever, the elevation of pCREB was inhibited by the GTS co-treatment. It has been suggested that NMDA receptor and/or NO is involved in the penomena of opioid dependence and withdrawal. However, the level of nNOS and NR1 was not modulated by the treatment with nalbuphine or GTS on the cortex, hippocampus and striatum in the rat brain. These results suggest that the GTS could be used to ameliorate the nalbuphine tolerance and withdrawal symptoms.

• The Korean Journal of Pain
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• v.10 no.1
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• pp.48-53
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• 1997

Background : Epidural morphine provides excellent postoperative analgesia but is often associated with side effects such as nausea, vomiting and pruritus. It has been reported that mixed agonist-antagonist, nalbuphine can reverse side effects of epidural morphine without compromising analgesia. This study was designed to compare the efficacy of each intravenous dose of nalbuphine for treatment of side effects following epidural morphine. Methods : All patients received continuous infusion(2 ml/hr) of epidural morphine-local anesthetics mixture(morphine 4 mg, 1% mepivacaine 50 ml and 0.25% bupivacaine 50 ml) following a loading dose (morphine 2 mg with 1% mepivacaine 7 ml). Patients requesting treatment for nausea, vomiting and pruritus randomly received intravenous nalbuphine 0.05 mg/kg(Group 1; n=20), 0.1 mg/kg(Group 2; n=20) or 0.15 mg/kg(Group 3; n=20). The severity of nausea, vomiting, pruritus, degree of pain, sedation and vital sign were assessed prior to and 30 min after each dose. Results : The severity of nausea, vomiting and pruritus decreased significantly in all groups(p<0.01). Pain and sedation scores were unchanged in all groups. One patient received nalbuphine 0.15 mg/kg, complained of dizziness, agitation and palpitation. His blood pressure who had increased to 170/100 after first dose. Conclusions : This study suggests that intravenous nalbuphine is good for treatment of side effects following epidural morphine, and the dose of Group 1, 0.05 mg/kg, may be recommended as an optimal dose.

• The Korean Journal of Pain
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• v.10 no.1
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• pp.34-41
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• 1997

Background : Patient-controlled analgesia(PCA) is a safe and effective technique for providing postoperative pain relief. Studies that compare epidural vs intravenous routes of opiate administration show conflicting results. We designed a prospective, randomized, controlled study to evaluate the safety and efficacy of epidural(EPI-PCA) morphine-bupivacaine versus intravenous (IV-PCA) nalbuphine when administered with a PCA system. Methods : Forty healthy women were randomly assigned to receive an epidural bolus of morphine 3 mg and 0.5% bupivacaine 10 ml, followed by a EPI-PCA with 0.01% morphine and 0.143% bupivacane (basal infusion 1 ml/hr, bolus 1 ml, lock-out interval 30 min) or intravenous bolus of nalbuphine 0.1 mg/kg followed by a IV-PCA with nalbuphine(basal infusion 1 mg/hr, bolus 1 ml, lock-out interval 20 min) for pain relief after cesarean delivery. This study was conducted for 2 days after cesarean section to compare the analgesic efficacy, side effects, patient satisfaction either as EPI-PCA or as IV-PCA. Results : EPI-PCA group had significant lower visual analog pain scale(VAS) at immediate postoperative period, whereas no significant difference was observed when pain was assessed at other time sequence. Urinary retention and pruritus were more frequent with EPI-PCA group, although the incidence of other side effects were the same. Conclusions : Although EPI-PCA with morphine-bupivacaine was of significantly lower VAS at immediate postoperative period, IV-PCA with nalbuphine is a safe and effective alternative to EPI-PCA with morphine-bupivacaine for providing pain relief after cesarean delivery. Further studies about IV-PCA with nalbuphine are needed to control the immediate postoperative pain and to further improve effective pain management.

• The Korean Journal of Pain
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• v.13 no.1
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• pp.38-43
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• 2000

Background: Preemptive analgesia may decrease postoperative pain by preventing nociceptive inputs generated during surgery. The preemptive effect of intravenous nalbuphine was examined in gynecological surgery. Methods: Forty female patients scheduled for gynecological surgery were randomly allocated into two groups. Each patient received 10 mg of intravenous nalbuphine as a bolus dose at the closure of peritoneum in group I (n=20) and before the skin incision in group II (n=20). After the bolus dose, the intravenous patient controlled analgesia (IV-PCA) which contained 50 mg of nalbuphine, 120 mg of ketorolac, 0.25 mg of droperidol and 90 ml of 5% dextrose water was given continuously at the rate of 2 ml/min. The postoperative visual analogue scale pain score (VAS), the total amount of the analgesics used, the degree of satisfaction of the patients and the developement of side effects were examined for 2 days. Results: VAS were significantly lower in group II than in group I after 9 and 12 hours. The cumulative consumption of analgesics in group II was significantly less than in group I. Most patients were satisfied with this regimen. There were no remarkable side effects. Conclusions: Preemptive analgesia with intravenous nalbuphine decreased postoperative pain and analgesic requirement. The analgesic effect of IV-PCA with nalbuphine-ketorolac was effective in control of postoperative pain in gynecologic surgery.

• The Korean Journal of Pain
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• v.7 no.2
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• pp.181-187
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• 1994

The MAC($ED_{50}$)values of enflurane, fentanyl, and nalbuphine-enflurane under 65% $N_2O$ were determined in 76 Sprague-Dawley rats using the tail-clamp technique to compare the equipotent effects of intravenous and inhaled anesthetics. The rats were divided into 3 groups: enfluarne, fentanyl, and nalbuphine-enflurane. Results were as follows: 1) The MAC value of enflurane under 65% $N_2O$ was $1.160{\pm}0.05%$ and after subcutaneous nalbuphine 20 mg/kg injection, the values were 1.08% at 60min and 0.99% at 90min. 2) The lowest $ED_{50}$ for fentanyl was 26.8 ${\mu}g$/kg at 15 min, and the $ED_{50}$, 30, 45, and 60min after the injection were 36.2, 39.7, and 44.7 ${\mu}g$/kg, respectively. 3) On arterial blood gas analysis under 65% $N_2O$-1MAC($ED_{50}$), fentanyl and nalbuphine-enflurane groups showed mild increase in $PaCO_2$, but there were no significant differences among 3 groups. Fentanyl group showed significant difference in pH compared with enfluarane and nalbuphine-enflurane groups. 4) Rats injected with high dose fentanyl(above $40{\mu}g$) displayed rigidity and respiratory depression.

• Biomolecules & Therapeutics
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• v.13 no.1
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• pp.13-19
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• 2005

The study was undertaken to determine the antagonism of the AP1700 on the development of nalbuphine-induced tolerance and physical dependence. AP1700 is an oriental drug preparationcomposed of 5 natural products and is known to have antinarcotic action with an oral dose of 250 mg/kg in rats. AP1700 significantly inhibits the development of antinarcotic action with an oral dose of 250 mg/kg in rats. AP1700 significantly inhibits the development of nalbuphine-induced physical dependence but does not the tolerance. Mitogen-activated protein kinase, which include extracellular signal-regulated kinase (ERK), p38 and c-Jun N-terminal kinase (JNK)/stress-activated protein kinase (SAPK) play critical roles in cell growth and survival and drug abuse. The level of pCREB was elevated in the hippocampus by the chronic treatment with nalbuphine, however, the elevation of pCREB was not inhibited by the AP1700 co-treatment. Interestingly, the level of pERK was decreased in the co-treatment with nalbuphine and AP1700 on the cortex and striatum. However, the level of nNOS and NR1 was not modulated by the treatment with nalbuphine or AP1700 on the cortex, hippocampus and striatum in the rat brain. These results suggest that the AP1700 could be used to ameliorate the nalbuphine withdrawal symptoms.

• The Korean Journal of Pain
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• v.10 no.2
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• pp.196-202
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• 1997

Background: Various pain treatments have been administered to relieve patients suffering from postoperative pain. Among these, epidural or intravenous opiate administration is by far the most widly applied treatment in recent times. However it was our objective to device a more effective and safe means of postoperative analgesia. Methods: We studied 110 healthy pregnant women scheduled for delivery by elective cesarean section. EPI(epidural)-group is administered morphine 1.5 mg and 0.25% bupivacaine 8 ml as bolus dose, then, a mixture of morphine 6 mg and 0.125% bupivacaine 95 ml as continuous dose via epidural route. IV(intravenous)-group is administered nalbuphine 6~7 mg as bolus dose and nalbuphine 60~70 mg with 0.9% normal saline 90 ml as continuous dose via intravenous route, at the rate of 2 ml/hr for 2 days. We compared the analgesic efficacy and side effects of these two groups using VAS pain score and time duration of constant pain level. Results: VAS pain score was similar between the two groups, but pain duration was significantly shorter in EPI-group. Incidence of pruritus was significantly lower with the IV-group, of nausea and vomiting were similar for both groups, no respiratory depression for either groups. Conclusions: Although the EPI-group had better analgesic efficacy, the IV-group had lower incidence of side effects, and simplicity and safety methods of operation. Therefore, We propose further research and consideration of administering the kinds and doses of those medications prescribe to the IV group in conjunction with other drugs for safer and better efficacy of postoperative analgesia.

• Korean Journal of Biological Psychiatry
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• v.6 no.2
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• pp.193-201
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• 1999

This study was designed to evaluate the effects of opioid receptor agonists on the spontaneous alternation behaviour in an animal model of obsessivecompulsive disorder in rats. According to the theory that dopamine is related to the biological etiology of obsessive-compulsive disorder, the effect of the nalbuphine(opioid kappa agonist) and the tramadol(opioid mu agonist), which act as manipulating agents on the inhibition or stimulation of dopamine release, in the spontaneous alternation behaviour were evaluated. 24 hours prior to the experiment, rats were food-deprived. These rats were put into the T-maze, in which white and black goal boxes were baited with small amounts of chocolate milk. Each rat was given 2 set of 7 trials during which it was placed in the start box and allowed to choose the one of the goal boxes for each time. After identifying the stable baseline of spontaneous alternation behaviour, nonselective 5-HT agonist 5-MeODMT(1.25mg/kg/IP) disrupted spontaneous alternation. Rats were stratified into fluoxetine(10mg/kg/IP), nalbuphine(10mg/kg/IP), tramadol(46.4mg/kg/IP), and saline(0.5cc/IP) injection group with experimental drug treatment for 21 days. The effects on the 5-MeODMT(1.25mg/kg/IP) induced disruption of spontaneous alternation behaviour were checked at the next day of discontinuation of drug treatment. The results were as follows ; 1) At the day after 21 days of the drug treatment, the nalbuphine treated group and the fluoxetine treated group showed significant difference from the tramadol treated group and the saline treated group in the 5-MeODMT(1.25mg/kg/IP) induced suppression of spontaneous alternation behaviour. 2) Within each drug treatment group, the fluoxetine treated group showed significant difference between before and after the treatment of fluoxetine in the 5-MeODMT(1.25mg/kg/IP) induced suppression of spontaneous alternation behaviour. And also, the nalbuphine treated group showed significant difference between before and after the treatment of nalbuphine in the 5-MeODMT(1.25mg/kg/IP) induced suppression of spontaneous alternation behaviour. There was no difference between the baseline and after the treatment of nalbuphine in the 5-MeODMT(1.25mg/kg/IP) induced suppression of spontaneous alternation behaviour. We indentified that the opioid kappa agonist that act as dopamine release inhibitor affect the spontaneous alternation behaviour which is an animal model of obsessive-compulsive disorder in rat.

• Journal of Korean Neurosurgical Society
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• v.30 no.12
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• pp.1394-1398
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• 2001

Objective : The purpose of this non-randomized prospective study was to evaluate the safety and efficacy of continuous intravenous nalbuphine-ketorolac-droperidol(CIA) versus continuous infusion of epidural morphine-bupivacaine(CEA) for pain control after lumbar spinal surgery. Methods : Twenty-one patients who underwent spine surgery including laminectomy, fusion with fixation were assigned to receive an intravenous bolus of nalbuphine 5mg and ketorolac 15mg, followed by a continuous infusion of nalbuphine 25mg, ketorolac 105mg, and droperidol 5mg mixed with normal saline 98cc(2cc/hr). Twenty patients received a bolus infusion of morphine 2mg and 0.125% bupivacaine 8cc followed by a continuous intravenous infusion of 100cc 0.125% bupivacaine and morphine sulfate 8.0mg(2cc/hr). Pain score was measured on a visual analogue scale(VAS). It's safety and efficacies were compared with the results of continuous infusion of epidural morphine-bupivacaine, which was reported previously by same authors. A continuous infuser was used to give epidural morphine-bupivacaine and intravenous nalbuphine-ketorolac-droperidol. Results : In general, mild pain, pain less than 3 VAS scores, was observed postoperatively from 30minutes to 72hours in CEA group, and from 6 hours to 72 hours in CIA group. The early postoperative pain was controlled easily in 6 hours in CEA group, compared to CIA group(p<0.05). However, there was no statistical significance in 72 hours on pain scores between CEA and CIA groups after 6-12hours of pain managements. Pruritus, nausea and vomiting, and urinary retention were more frequent in CEA group. Conclusion : CIA and CEA are considered effective methods in postoperative pain managements. However, adequate doses in early intravenous infusion and continuous intravenous analgesia with nalbuphine-ketorolac-droperidol will be needed for better control in early postoperative pain with less side effects.