Effects of Low-dose Naloxone on Postoperative Analgesia and Side Effects in Intravenous Patient-Controlled Analgesia after a Total Hysterectomy / 대한마취과학회지

BACKGROUND: Naloxone is an opioid antagonist and effective in reducing and reversing opioid-related side effects. In addition, low-dose naloxone may reverse or potentiate the analgesic effect of an opioid. The present study was designed to examine the analgesic efficacy and side effects of the combination of naloxone with morphine in patients using intravenous PCA (patient-controlled analgesia). METHODS: Patients were randomly assigned to receive one of three PCA regimens: group 1 (40 mg morphine + 90 mg ketorolac + 2.5 mg dorperidol), group 2 (40 mg morphine + 90 mg ketorolac + 0.8 mg naloxone), or group 3 (40 mg morphine + 90 mg ketorolac + 1.6 mg naloxone). All patients were given an initial loading dose of 0.1 mg/kg morphine at the end of surgery. Pain scores, side effects, and overall satisfaction were assessed at 30 min, 1, 8, 24 and 48 hr postoperatively. Blood pressure, heart rate, and respiratory rate were also monitored for 48 hours. RESULTS: The pain score was significantly lower in group 2 than in group 1 and group 3 at 8 hr and 24 hr postoperatively. Cumulative morphine usage during 48 hr was the least in group 2 compared with group 3. There were no differences in the overall incidence of side effects, patient satisfaction, and hemodynamic parameters among the groups. CONCLUSIONS: The present results suggest that a low-dose naloxone with intravenous morphine PCA is effective in reducing opioid-related side effects and in increasing the quality of analgesia.

A Comparison of the Analgesic and Side Effects of Continuous Epidural Morphine and Nalbuphine after a Cesarean Section / 대한마취과학회지

BACKGROUND: Epidural morphine has been commonly used to provide postoperative pain relief, but it has many side effects such as pruritus, nausea, vomiting, and respiratory depression. The purpose of this study was to evaluate the analgesic efficacy and side effects of epidural morphine compared with epidural nalbuphine. METHODS: Fifty nine patients were randomly divided into 2 groups. For group M (n = 30), a bolus of 7 ml of saline and 2 mg of morphine were administered and for group N (n = 29), a bolus of 7 ml of saline and 4 mg of nalbuphine were administered. Continuous epidural analgesia was induced with morphine 4 mg, 0.5% bupivacaine 20 ml, 2% lidocaine 20 ml and normal saline 60 ml by a 2day infuser in group M, and with nalbuphine 20 mg, 0.5% bupivacaine 20 ml, 2% lidocaine 20 ml and normal saline 58 ml by a 2day infuser in group N. We compared the analgesic effect and side effects of the two groups for 48 hours. RESULTS: No significant hemodynamic changes were seen in any of the groups. The analgesic effects were good in the two groups (mean VAS < 3.0). The patients of group M had lower pain scores continually compared with group N and pain scores were statistically significant at 6, 12 and 24 hours. However, side effects occurred more frequently in group M. CONCLUSIONS: These results suggest that an adequate dosage of epidural morphine provides good analgesic effects and reduces the occurrence of side effects.

The Mechanism of Antiallodynic Effect of Intrathecal Morphine in Neuropathic Pain Induced by Spinal Nerve Ligation / 대한마취과학회지

BACKGROUND: Although the efficacy of morphine in a neuropathic pain state is somewhat controversial, intrathecally administered morphine reversed the mechanical allodynia in a previous animal study. Using a behavioral test, we investigated the mechanism of the antiallodynic action of intrathecal morphine by administering opioids, alpha2 adrenergic and cholinergic receptor antagonists in a rat model of neuropathic pain induced by a spinal nerve ligation injury. METHODS: Male Sprague Dawley rats were prepared with a tight ligation of the left lumbar 5th and 6th spinal nerves and insertion of a chronic lumbar intrathecal catheter. Morphine 1 microgram was administered intrathecally to attenuate the mechanical allodynia. Naloxone 10 microgram, yohimbine 30 microgram, prazosin 30 microgram, atropine 10 microgram, pirenzepine 10 microgram, and methoctramine 10 microgram was administered intrathecally before and after the injection of morphine in order to investigate the reversal of an increased allodynic threshold by morphine. The allodynic thresholds for the left hindpaw withdrawal to von Frey hairs were assessed and converted to %MPE. RESULTS: A reduction of mechanical allodynia by intrathecal morphine was produced. Naloxone pretreatment, but not posttreatment, reversed the antiallodynic effect of intrathecal morphine (P < 0.01). All alpha2 adrenergic and cholinergic receptor antagonists used here did not reverse it. CONCLUSIONS: The results suggest that the reversal mechanism of mechanical allodynia by intrathecal morphine appears to be mediated mostly by the opioid receptor system, but not the alpha2 adrenergic and cholinergic receptor systems, at the spinal level in a rat model of a spinal nerve ligation injury.

Receptor Activation is Not the Main Rescue Mechanism of Morphine in Peroxynitrite-Induced Death of Human Neuroblastoma SH-SY5Y Cells / 대한마취과학회지

BACKGROUND: In the present study, we examined the effect of morphine on NO- and peroxynitrite-induced cell death using a human neuroblastoma SH-SY5Y cell line which abundantly expresses micro, delta and K-opioid receptors. METHODS: The cultured cells were pretreated with morphine (100 micrometer) and exposed to 3-morpholinosydnonimine (SIN-1, 1mM). Agarose gel electrophoresis of DNA was done with the extracts from SH-SY5Y cells. The cells were treated with selective ligands for opioid receptor subtypes and with PI3-kinase inhibitors. Cell damage was assessed by using an MTT assay. Spectrophotometric absorption spectra were measured from the mixture of morphine (100 micrometer) plus peroxynitrite (1 mM) at room temperature. RESULTS: SIN-1 treated cells showed the occurrence of a specific form of chromosomal DNA fragmentation which pretreatment with morphine inhibited. The selective ligands for opioid receptor subtypes, [D-Ala2, N-Me-Phe4, Gly-ol5]enkephalin (DAMGO, micro-opioid receptor agonist), [D-Pen2,5] enkephalin (DPDPE, delta-opioid receptor agonist) and U-69593 (K-opioid receptor agonist) at a concentration of 10 micrometer did not prevent the cell death induced by SIN-1. Naloxone (20 micrometer) hardly antagonized the effect of morphine in SIN-1-induced cell death. The PI3-kinase inhibitors Wortmannin and LY294002 did not inhibit the action of morphine on apoptotic cell death. In the measurements of spectrophotometric absorption spectra, the peak of the absorbance of the mixture of morphine plus peroxynitrite at 295 300 nm disappeared three minutes after mixing. CONCLUSIONS: The present study showed that morphine protected the human neuroblastoma cell line,SH-SY5Y, from peroxynitrite-induced apoptotic cell death. However, it is suggested that the protective action of morphine is not via the activation of opioid receptors and/or the PI3-kinase pathway but possibly via direct chemical reaction.

The Effect of Morphine on Pain and Bowel Function after Colonic Surgery:Epidural Bupivacaine-morphine Versus Intravenous Patient-controlled Analgesia with Morphine / 대한마취과학회지

BACKGROUND:Gastrointestinal paralysis after abdominal surgery has long troubled both patients and surgeons. Gastrointestinal side effects still constitute a major drawback in the acute use of opioids. Choice of postoperative analgesia may affect the rate of recovery of gastrointestinal function. The purpose of the present study was to investigate the influence of intravenous and epidural morphine on recovery of bowel function and pain by measuring intestinal motility and the visual analogue scale after colon surgery. METHODS: Twenty patients undergoing colon surgery used postoperative pain contol. Patients were allocated to receive either IV PCA (patient-controlled analgesia) with morphine or CEA (continuous epidural analgesia) with 0.1% bupivacaine-0.04% morphine. Patients were assessed for pain with a visual analogue scale, and for side effects at 1, 6, 12, 24, 48 hours postoperatively. Arterial blood samples for the measurement of blood gas and plasma concentration of morphine were taken. The time to first postoperative passage of flatus and feces, length of nasogastric therapy, time to liquid, soft and solid food intake, daily and total morphine requirement and length of hospital stay were recorded. RESULTS: There were no significant differences in bowel movement outcome except in length of nasogastric therapy, but the CEA group had significantly lower pain scores and required fewer days of nasogastric therapy when compared with the IV PCA group. CONCLUSIONS: These observations indicate that IV PCA with morphine and CEA can be used to relieve postoperative pain without prolonging the recovery of bowel movements, but CEA with bupivacaine and morphine constitutes an effective means of analgesia.

What is the Minimum Effective Dose of Propofol in Relieving Epidural Morphine Induced Pruritus? / 대한마취과학회지

BACKGROUND: Mu-receptor antagonists are considered effective for the treatment of epidural morphine induced pruritus (EMIP). However, they have been associated in certain cases with a concomitant reduction in analgesia. It is noteworthy that propofol has been shown to produce marked spinal depression, in particular of the dorsal and ventral horn. Recently it was reported that subhypnotic doses of propofol were efficient in relieving EMIP. This study was designed to investigate an effective minimum dose of propofol. METHODS: After obtaining informed consent from patients and with IRB approval, 155 patients having cesarean section received an epidural morphine 3 mg bolus, and 4 mg/day with continuous infusion for 2 days via a Baxter infusor(R). Patients who had pruritus with scratching were allocated randomly to one of the three groups. Patients received 10 mg propofol intravenously in group I (n = 25), 20 mg in group II (n = 25) and 30 mg in group III (n = 25). Pruritus and the level of sedation were assessed 5 minutes later using 5 points pruritus rating scale (PRS) and 4 points sedation rating scale (SRS). Statistical analysis was performed using chi-square test, one-way ANOVA and paired t-test. P or = 3). The success rate was significantly greater in the group II (76%) and group III (80%) than in the group I (48%) (P < 0.05). Seven patients had an increase in sedation in the group III versus none in the group I and group II (P < 0.05). The beneficial effect of treatment was longer than 60 minutes in 100% of patients in group I, II and III. CONCLUSION: These results suggest that 20 mg propofol and 30 mg propofol intravenously are equally effective in treating EMIP than 10 mg propofol. However the level of sedation is significantly less in 20 mg propofol group than 30 mg propofol group.

The Effects of Intraoperative Epidural Morphine on Postcesarean Intravenous Patient-Controlled Analgesia / 대한마취과학회지

BACKGROUND: Intravenous patient-controlled analgesia (IV-PCA) has been widely used for pain relief after cesarean delivery under epidural anesthesia. However, IV-PCA alone has a limited effect on early postoperative pain relief. Epidural morphine injected intraoperatively could alleviate the early postcesarean pain. We evaluated the effects and side effects of intraoperative epidural morphine on postoperative IV-PCA. METHODS: Forty patients scheduled for cesarean section under epidural anesthesia were randomly assigned to one of two groups. The patients in the intravenous group (IV group, n = 20) received intravenous morphine 3 5 mg after the operation in the recovery room when patients complain of pain, and the patients in the epidural group (EPI group, n = 20) received intraoperative epidural morphine 3 mg after fetus delivery. After that, both groups received morphine IV-PCA (no basal infusion, bolus 1.0 mg, lock-out time 6 min). Analgesic efficacy, degree of patient satisfaction, drug consumption and side effects were compared at 4 and 24 hours after surgery. RESULTS: The EPI group had significantly lower VAS for pain at 4h after surgery on movement and resting than the IV group, whereas no significant difference was observed at 24h after surgery. The cumulative morphine consumptions at 4h and 24h after surgery were more in the IV group (each, P < 0.001). Fewer patients in the EPI group had drowsiness at 24h after surgery, but there were no significant differences in other side effects and degree of satisfaction between the two groups. CONCLUSIONS: We conclude that intraoperative epidural morphine was effective with less side effects for postoperative IV-PCA in the cesarean patients under epidural anesthesia.

Effects of Epidural Co-administration of Morphine and Naloxone on Intestinal Motility after Total Hysterectomy / 대한마취과학회지

BACKGROUND: Epidural morphine is usually associated with decreased bowel motility and increased transit time. Low doses of intravenous naloxone have been known to reduce morphine-induced side effects including intestinal hypomotility without reversing analgesia, but the effect of epidural naloxone has not been defined in human study. Therefore we evaluated bowel motility and analgesia when naloxone was administered via epidural route. METHODS: Forty-two patients having epiduro-general analgesia for total hysterectomy were randomly assigned to one of two study groups. As a means of postoperative pain control, all received 1.5 mg of epidural morphine bolusly 1 hour before the end of surgery, and a continuous epidural infusion was started using a two-day infusor containing 2.5 mg of morphine in 0.125% bupivacaine 100 ml with either no naloxone (control group, n = 20) or 5 microgram/kg/day of naloxone (experimental group, n = 22). We measured the time to the postoperative first passage of flatus and feces to evaluate the restoration of bowel function, and visual analog scales (VAS) for pain during rest and movement. Scores were taken at 2 and 4 hours after the operation, 7 AM, 1 PM, and 7 PM of the 1st postoperative day and 7 AM and 1 PM of the 2nd postoperative day. RESULTS: The experimental group revealed less time to the first postoperative passage of flatus and feces. No significant difference was found in resting and movement VAS between the two groups. CONCLUSIONS: This study suggests that epidural naloxone reduces epidural morphine-induced intestinal hypomotility without reversing analgesic effects.

Morphine Protects Peroxynitrite-induced Cell Death in Primary Rat Neonatal Astrocytes / 대한마취과학회지

BACKGROUND: Astrocytes, representing a major non-neuronal cell population in the central nervous system (CNS), contain opioid receptors and are actively involved in several brain functions. This study is designed to evaluate the effects by which morphine contributes to cytotoxicity of nitric oxide (NO) species including NO and peroxynitrite (ONOO(-)) in primary astrocytes isolated from the cerebral cortexes of 1 - 2 day Sprague-Dawley rats. METHODS: The cultured cells were pretreated with morphine and exposed to 3-morpholinosydnonimine (SIN-1) which simultaneously generates NO and superoxide, thus possibly forming peroxynitrite. The cell damage was assessed by using an MTT (methylthizol-2-yl-2, 5-diphenyl, tetrazolium bromide) assay. Morphological nuclear changes of the cells after exposure to SIN-1 for 24 hours was evaluated by using 4', 6-diamidino-2-phenylindole (DAPI) staining. RESULTS: Morphine significantly protected primary rat astrocytes in a dose-dependent manner from the death mediated by sodium nitroprusside (SNP), a donor of nitric oxide, and SIN-1. Moreover, it was found that naloxone antagonized the protective effect of morphine on SIN-1-induced cell death, revealed as apoptosis by the occurrence of morphological nuclear changes characteristic of apoptosis. Morphine also inhibited the nuclear condensation of SIN-1-treated cells, however the action of morphine was antagonized by pretreatment of naloxone. The protective role of morphine on SIN-1-induced cytotoxicity was inhibited by DL-Buthionine-[S, R]-sulfoximine (BSO). Furthermore, the effects of morphine on SIN-1-induced cytotoxicity were blocked by pretreatment of Gi protein inhibitor, pertussis toxin, and phosphoinositide 3-kinase (PI3 kinase) inhibitors, Wortmannin and LY294002. CONCLUSIONS: These results suggest that morphine may protect primary rat astrocytes from NO species via the signaling cascades involving G-protein and PI3-kinase, and possibly regulates the anti-oxidant, glutathione (GSH).

Effects of Morphine on Free Radical-induced Apoptosis of Human Neuroblastoma SH-SY5Y Cells / 대한마취과학회지

BACKGROUND: The effect of opioids on nitric oxide (NO)- and peroxynitrite-induced neuronal cell death is largely unknown. In the present study, we examined the effect of morphine on NO- and peroxynitrite-induced cell death using a human neuroblastoma SH-SY5Y cell line, which abundantly expresses micro, delta, kappa-opioid receptors. METHODS: The cultured cells were pretreated with morphine and exposed to 3-morpholinosydnonimine (SIN-1) that simultaneously generates NO and superoxide, thus possibly forming peroxynitrite. The cell damage was assessed by using MTT assay and crystal violet staining. Morphological nuclear changes and enzymatic evidences of apoptosis of the cells after exposure to SIN-1 for 24 hours were evaluated by using 4', 6-diamidino-2-phenylindole (DAPI) staining and the measurement of pro-apoptotic protease (caspase-3) activity, respectively. Levels of reduced glutathion (GSH) were measured by monochloronimane (MCB) assay. RESULTS: Pretreatment of SH-SY5Y with morphine significantly inhibited the apoptotic cell death. Morphine also inhibited SIN-1-induced caspase-3 (pro-apoptotic protease) activity in a dose-dependent manner. However, naloxone (20 microM) could not antagonize completely the effect of morphine in SIN- 1-induced cell death. Pre-administered GSH and N-acetylcysteine (NAC) have been found to protect SIN-induced apoptosis, and the neuroblastoma cells treated with morphine had significantly elevated the levels of GSH. CONCLUSIONS: The present study shows that morphine protects the human neuroblastoma cell line SH- SY5Y from peroxynitrite-induced apoptotic cell death through elevated GSH levels. The protective actionof morphine seems to be associated with inhibition of the apoptotic pathway. However, it is suggested that morphine protects the cells possibly via other unknown mechanisms in addition to the activation of opioid receptors.

Patient Controlled Analgesia Using Surgical Wound Infusion / 대한마취과학회지

BACKGROUND: This study was undertaken to evaluate the analgesic effect of a self administered surgical wound infusion of local anesthetic alone compared to combination of local anesthetic and morphine or ketorolac. METHOD: Forty eight patients undergoing minor surgery were randomly classified into four groups: Group 1 (saline, n = 10), Group 2 (bupivacaine only, n = 11), Group 3 (bupivacaine with morphine, n = 14), and Group 4 (bupivacaine with ketorolac, n = 13). A two-hole 19 G epidural catheter was tunneled subcutaneously into the surgical wound and was connected to 100 ml elastometric balloon pump filled with either 0.5% bupivacaine only, 0.5% bupivacaine and morphine 40 mg, or 0.5% bupivacaine and ketorolac 80 mg. We assessed the postoperative visual analogue scale (VAS) pain scores at postoperative 0.5, 1, 2, 6, 12, 24, 36, and 48 hours, and the side effects, sedation score and total amount of infused bupivacaine were recorded. RESULTS: VAS pain score were significantly decreased until 36 hours in groups 2, 3, and 4 compared to group 1, and significantly lower at 1, 2, 12, and 24 hrs in groups 3, 4 than in group 2 (P < 0.05). The total requirement of infused bupivacaine in groups 3, 4 is significantly decreased compared to that of group 2. Side effects like nausea, vomiting, urinary retension, pruiritis, respiratory difficulty, sedation, and dizziness did not occur in the four groups but seroma did in one case. CONCLUSION: Patient-controlled surgical wound infusion of bupivacaine reduced postoperative pain after minor surgery without any side effects. The combination of bupivacaine with morphine or ketorolac gave rise to a significant additive effect to local analgesia.

The Effect of Intraarticular Morphine and Clonidine on Postoperative Analgesia after Knee Surgery / 대한마취과학회지

BACKGROUND: Intraarticular bupivacaine, clonidine and morphine produce good postoperative analgesia. This study was designed to compare the analgesic effects of intraarticular clonidine and morphine, used separately and in combination. METHODS: We studied 60 patients undergoing arthroscopic anterior cruciate ligament reconstruction of knee under spinal anesthesia using hyperbaric bupivacaine. Each patients received 30 ml of intraarticular 0.25% bupivacaine containing clonidine 150 g or morphine 2 mg or both. RESULTS: There were no differences in VAS scores at 0, 1, 2, 6, 12, 24, 36, 48 hr after operation and the dosage of postoperative analgesics among the groups. CONCLUSIONS: We concluded that 30 ml of 0.25% bupivacaine containing morphine 2 mg or clonidine 150 g provided comparable analgesia after intraarticular administration, but the combination of these drugs did not seem to increase analgesia.

A Study of Epidural Droperidol Dosage for Reducing Nausea, Vomiting and Pruritus Due to Epidural Morphine and Fentanyl in Epidural Pain Management of Patients Undergoing Vaginal Total Hysterectomy / 대한마취과학회지

BACKGROUND: Epidural pain control has been used extensively for postoperative pain management, but nausea, vomiting and pruritus associated with morphine and fentanyl administration remain intractable problems. The aim of this study is to find the optimal epidural droperidol dosage for reducing the side effects of epidural morphine and fentanyl. METHODS: 140 patients randomly sampled and undergoing vaginal total hysterectomy were divided into 7 groups. Groups I and IV, and groups II and V, and groups III and VI, received 5 mg, 3.75 mg, 2.5 mg of droperidol by 2-day infusion pump through the indwelling epidural catheter, respectively. Group IV, V, VI patients received 1.25 mg of bolus droperidol through the indwelling epidural catheter at the time of peritoneal closure. As group VII was the control group, these patients received only epidural analgesics (morphine 10 mg, fentanyl citrate 300 microgram and 0.05% bupivacaine 100 ml) by 2-day infusion pump. RESULTS: Droperidol significantly reduced the incidence and severity of postoperative nausea, vomiting and itching sensation compared with the control group but verbal rating scale (VRS) of sedation was increased with the dosage of droperidol. There was no significant difference in the intensity of analgesia between the there groups. CONCLUSIONS: An effective epidural droperidol dosage for reducing postoperative nausea, vomiting and pruritus due to epidural pain control is 2.5 mg by 2-day infusion pump.

A Study of Epidural Droperidol Dosage for Reducing Nausea, Vomiting and Pruritus Due to Epidural Morphine and Fentanyl in Epidural Pain Management of Patients Undergoing Vaginal Total Hysterectomy / 대한마취과학회지

BACKGROUND: Epidural pain control has been used extensively for postoperative pain management, but nausea, vomiting and pruritus associated with morphine and fentanyl administration remain intractable problems. The aim of this study is to find the optimal epidural droperidol dosage for reducing the side effects of epidural morphine and fentanyl. METHODS: 140 patients randomly sampled and undergoing vaginal total hysterectomy were divided into 7 groups. Groups I and IV, and groups II and V, and groups III and VI, received 5 mg, 3.75 mg, 2.5 mg of droperidol by 2-day infusion pump through the indwelling epidural catheter, respectively. Group IV, V, VI patients received 1.25 mg of bolus droperidol through the indwelling epidural catheter at the time of peritoneal closure. As group VII was the control group, these patients received only epidural analgesics (morphine 10 mg, fentanyl citrate 300 microgram and 0.05% bupivacaine 100 ml) by 2-day infusion pump. RESULTS: Droperidol significantly reduced the incidence and severity of postoperative nausea, vomiting and itching sensation compared with the control group but verbal rating scale (VRS) of sedation was increased with the dosage of droperidol. There was no significant difference in the intensity of analgesia between the there groups. CONCLUSIONS: An effective epidural droperidol dosage for reducing postoperative nausea, vomiting and pruritus due to epidural pain control is 2.5 mg by 2-day infusion pump.

Comparison of Subcutaneous Patient-Controlled Analgesia with Intravascular Patient-Controlled Analgesia Using Morphine / 대한마취과학회지

BACKGROUND: Generally, for patients with cancer, chronic disease, burn injury or pediatric patients to whom oral medication is difficult or whose vessels are fragile, it is difficult to inject analgesics parenterally. To know the effect of subcutaneous infusion which would be directly used by patients themselves or their care givers, we compared subcutaneous patient-controlled analgesia (SQ PCA) with intravenous patient-controlled analgesia (IV PCA) morphine for acute postoperative pain. METHODS: We undertook a study to prospective, randomized, controlled patients (n = 30) undergoing elective total hysterectomy to compare SQ PCA with IV PCA morphine for postoperative pain control. We prepared a 5 mg/ml solution of morphine for the SQ PCA group (n = 15) and a 1 mg/ml solution of morphine for the IV PCA group (n = 15). The regimen of morphine was a basal rate 20 microgram/kg/h, 1 mg bolus, 10 min lockout interval, 1 hour limit of 8 mg. We evaluated the VAS score at rest and at coughing after postoperative 6, 12, 18, 24, 30, 36, 42 and 48 hours, 6 hourly doses of morphine, total requirement of infused morphine for 48 hours and delivery to demand ratio. Side effects and satisfactory score were checked too. RESULTS: The Visual analogue scale (VAS) pain score at rest and with coughing, the 6 hourly doses of morphine, the total requirement of infused morphine for 48 hours, the delivery to demand ratio, side effects and the satisfactory score were not significantly different in the two groups (P<0.05). CONCLUSION: Thus SQ PCA morphine represents a clinically acceptable alternative to IV PCA in the treatment of postoperative pain control.

Comparison of Onset Time and Postoperative Analgesic Effects of Mepivacaine and Bupivacaine with Morphine on Caudal Block / 대한마취과학회지

BACKGROUND: Caudal injection of local anesthetics with morphine is the most common anesthetic technique for perianal operation and postoperative analgesia. This study was purposed to compare the onset time of caudal analgesia, postoperative analgesic effect and side effects. METHOD: Sixty healthy patients scheduled for perianal operation were divided into 2 groups randomly. Group I was given 2 mg of morphine in 20 ml of 2% mepivacaine via sacral hiatus. Group II was also given 2 mg of morphine in 20 ml of 0.5% bupivacaine caudally. We measured the onset time of caudal block, time to the first request of analgesics, the number of analgesics within 24 hours and the incidence of postoperative side effects. Analgesic effect was evaluated by visual analogue scales (VAS) at 1, 2, 6, 12 and 24 hours postoperatively. RESULT : The onset time of caudal block for operation and the first request time of analgesic for postoperative pain was significantly shorter in group I than group II. The analgesic use in the first 24 hours was significantly more in group I than group II. The side effects were similar in both groups. CONCLUSION: We concluded that the combined use of morphine and bupivacaine provided better postoperative analgesia than the combined use of morphine and mepivacaine.

Effects of Epidural Naloxone on Intestinal Hypomotility Caused by Epidural Morphine after Gastrectomy / 대한마취과학회지

BACKGROUND: Epidural morphine is usually associated with decreased bowel motility and increased transit time. Low doses of intravenous naloxone have been known to reduce morphine-induced side effects including intestinal hypomotility without reversing analgesia, but the effect of epidural naloxone has not been defined in any human study. Therefore, we evaluated bowel motility and analgesia when naloxone was administered via the epidural route. METHODS: Forty patients having epiduro-general analgesia for subtotal gastrectomy were randomly assigned to one of two study groups. As a means of postoperative pain control, all received 1.5 mg of epidural morphine bolusly 1 hour before the end of surgery, and a continuous epidural infusion was started using a two-day infusor containing 2.5 mg of morphine in 0.125% bupivacaine 100 ml with either no naloxone (control group, n=20) or 5 microgram/kg/day of naloxone (experimental group, n=20). We measured the time to the first postoperative passage of flatus and feces to evaluate the restoration of bowel function, and visual analog scales (VAS) for pain, during rest and movement. Scores were taken at 2 and 4 hours after the operation, 7 AM, 1 PM, and 7 PM of the 1st postoperative day and 7 AM and 1 PM of the 2nd postoperative day. RESULTS: The experimental group revealed less time to the first postoperative passage of flatus and feces. No significant difference was found in resting and movement VAS between two groups. CONCLUSION: This study suggests that epidural naloxone reduces epidural morphine-induced intestinal hypomotility without reversing analgesic effects.

The Effects of Morphine on the Sensory Receptors in the Acutely Inflamed Feline Urinary Bladder / 대한마취과학회지

BACKGROUNDS: Pain can occur following acute noxious stimuli and tissue damage. The duration of such pain may outlast the stimulus and its amplitude may be exaggerated (hyperalgesia). This response comes from a sensitization of the peripheral nociceptor. Traditional thought has associated the antinociceptive effects of opiates with the activation of opioid receptors located in the central nervous system. Recently, however, opiate receptors in the peripheral nervous system have led to the hypothesis that analgesic action might, in part, result from a reduction in the response of peripheral nerve fibers thought to be concerned with signaling pain. METHODS: Twenty units were recorded from the strands of the hypogastric nerve innervating the urinary bladder of the cat. Nerve activity and intravesical pressure were monitored before and after the onset of an acute inflammation induced by the intravesical instillation of 2% mustard oil. The responses of afferent units to chemical stimuli by intra-arterially injected bradykinin (10 microgram/0.2 ml., i.a.) and potassium chloride (0.3 M/0.2 ml, i.a.) were compared each time at control, after inflammation, and after administration of morphine (2.5 mg/kg) and naloxone (5 microgram/kg) respectively. RESULTS: Polymodal receptors in the urinary bladder showed excitatory response to algesic substances such as bradykinin, potassium chloride and the urinary bladder contracted simultaneously, both the responses of the nerve impulse and bladder contraction to bradykinin and potassium chloride increased significantly after bladder inflammation induced by 2% mustard oil and the sensitization of the sensory receptors attenuated by morphine and naloxone reversed the effect of morphine. CONCLUSIONS: These observations suggest that morphine might have a peripheral effect.

The Effect of Continuous Thoracic Epidural Administration of Morphine with Bupivacaine after Thoracotomy / 대한마취과학회지

BACKGROUND: The purpose of this study was to evaluate the analgesic effect and side effects including respiratory depression and cardiovascular changes after continuous high thoracic epidural infusion of morphine when given with bupivacaine for postthoracotomy pain. METHODS: In a prospective study, 25 patients who received continuous thoracic epidural administration of morphine with bupivacaine after thoracotomy were studied. The analgesia was provided by a continuous epidural infusion for 2 days. Initially, 0.25% bupivacaine 5~7 ml with morphine 1 mg was injected epidurally. Then, continuous epidural infusion of 0.25% bupivacaine 2 ml/hr with morphine 0.125 mg/hr was followed. RESULTS: The pain score (visual analogue pain scale) was below 3 at all postoperative periods except postoperative 1 hour with cough. The significant PaCO2 and cardiovascular changes for 2 days after epidural injection were not occured. There were no significant side effects requiring treatment. CONCLUSION: Continuous high thoracic epidural administration of 0.125 mg/hr of morphine with 0.25% bupivacaine is safe and effective analgesic method for thoracotomy.

Peripheral Effect of Morphine on Mechanical Allodynia in a Rat Model of Neuropathic Pain / 대한마취과학회지

BACKGROUND: The therapeutic effect of morphine on neuropathic pain states was controversial, but there are some reports that systemic morphine reduced pain. Recently, many investigators have reported that locally administered morphine alleviated pain in local inflammatory pain model. Therefore, we designed this study to evaluate the peripheral effect of morphine and its antagonism by naloxone in rats experiencing neuropathic pain. METHODS: Neuropathic pain was produced by tightly ligating the left 5 th and 6 th lumbar spinal nerves of male Spraw-Dawley rats. To evaluate the systemic effect, morphine 200 microgram was injected into the unaffected right paw. Morphine 50, 100 and, 200 microgram were injected into the affected left paw. Naloxone 5, 10 and 20 microgram were injected into the affected left paw ten minutes before morphine 200 microgram was injected into the affected left paw. Before and after drug injection, mechanical allodynia was quantified by the foot withdrawal frequency to von Frey filaments of 5.50 g or 1.48 g, applied to the affected left paw. RESULTS: Morphine 200 g injected into the unaffected right paw did not affect the foot withdrawal frequency on the affected left paw. Morphine 100 and 200 microgram decreased the foot withdrawal frequency. In rats with morphine 200 microgram injected into the left paw, naloxone 5, 10, and 20 microgram increased foot withdrawal frequency. Conclusion: These data represented that morphine injected into the affected paw dose-relatedly reduced mechanical allodynia via peripheral effect and pretreatment of naloxone significantly antagonized the morphine effect.