• The Korean Journal of Pain
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• v.9 no.1
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• pp.69-74
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• 1996

Background: Efficacy of spinal opioids for the treatment of intractable cancer pain has been reported by several authors. The epidural route seems to be a more reliable and effective method of pain control as compared to the intrathecal route which can lead to opioids by portal system. Methods: Medical records were reviewed of 18 patients who had been treated with epidural morphine via an implanted port-A-Cath from Mar. 1991 to Sep. 1994. Results: Patients were treated for a mean of 92 days. There were wide variation of dose requirements. The minimum daily dose ranged from 2 to 10mg, and maximum daily dose from 3 to 30 mg. Verbal rating scale were below moderate until 100th days after posrtal implantation. When 3 patients suffered from aggravated pain associated with vertebral metastasis. Five of 11 patients who were administered medication longer than 50 days reguired increased doses ranging from 3 mg to 25 mg which were higher as compared to initial doses. These patients also experienced pain due to vertebral metastasis. There were no report of epidural scarring, respiratory depression, epidural infections, meningitis, or catheter blockade. Conclusion: Continuous epidural morphine administration via Port-A-Cath is an effective method with minimal complication.

• Journal of Korean Academy of Nursing
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• v.38 no.5
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• pp.720-729
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• 2008

Purpose: This study investigated the preemptive analgesic effects of Morphine and Ketorolac on postoperative pain, cortisol, $O_2$ saturation and heart rate for the first 24 hr after abdominal surgery. Methods: Data collection was performed from April 1 to September 30, 2006. Forty patients undergoing a gastrectomy under general anesthesia were randomly allocated to the experimental or control group. The experimental group (20 patients) was administered Morphine and Ketorolac approximately 1 hr prior to skin incision, but the control group (20 patients) was administered Morphine and Ketorolac at peritoneum closure through a patient-controlled analgesia (PCA) pump. Postoperative pain, blood pressure, heart rate, cortisol, $O_2$ saturation, frequency of the PCA button pressed and doses of additional analgesics were observed through post operative 24 hr. Collected data was analyzed using t-test, $X^2$ test, repeated measures ANOVA, and Bonferroni methods. Results: Postoperative pain, cortisol, the frequency of PCA button pressed, and dose of additional analgesics of the experimental group were significantly lower than the control group. There were no statistical differences in blood pressure, heart rate and $O_2$ saturation between the experimental group and control group. Conclusions: We concluded that administration of morphine and ketorolac at 1 hr prior to skin incision resulted in decreasing postoperative pain, but it didn't affect blood pressure, heart rate or $O_2$ saturation for 24 hr after abdominal surgery.

• Clinics in Shoulder and Elbow
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• v.3 no.2
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• pp.102-108
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• 2000

The aim of this study is to determine if intra-bursal morphine and Bupivacaine mixed infusion provided useful analgesia after subacromial arthroscopic operation. At the end of the subacromial arthroscopy, continuous intra-bursal infusion catheter was inserted. In a double-blind randomized trial, Sixty patients were allocated to one of two groups: placebo group(n=30) received continuous saline infusion. Study group received mixed 5㎖ of 0.5% Bupivacaine, 2㎎ of morphine and 0.05㎖ of 1/1000 epinephrine as bolus and mixed solution of 40㎖ of 0.5% Bupivacaine and 8㎎ of morphine as maintenance dose with continuous infusion pump(0.5㎖ hourly). In the placebo group, two patients were discontinued due to leakage and catheter coming out each. Intensity of pain was evaluated preoperatively and postoperatively for 3 days by 10 graded visual analogue scale. Night pain, pain on motion, sleep disturbance, lying on painful shoulder and amounts of intramuscular pain killer were recorded. Analgesic effect for pain was cleared at 1st and 2nd postoperative day and there was less sleep disturbance for 3 days postoperatively in study group. There was no difference in pain on motion postoperatively. In study group, less pain killers were used in the first 48 hours postoperatively. The continuous intra-bursal infusion decreased perception of pain at resting stage and reduced supplemental analgesic requirement for 2 days postoperatively.

• The Korean Journal of Pain
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• v.19 no.1
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• pp.96-100
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• 2006

Pain control is very important in managing terminal cancer patients and there are several modalities to alleviate their pain. A high dosage of epidural morphine is effective to control terminal cancer pain. Furthermore, to decrease the amount of morphine, adding an alternative adjuvant like ketamine to the morphine regimen is considered helpful for controlling the pain of a terminal cancer patient. A 45 year old male patient with terminal lung cancer had neck pain that was caused by multiple bone metastases. Continuous epidural block was started with 2 mg/day of morphine and the dosage was gradually increased to 90 mg/day in 86 days. 30 mg/day of ketamine was then added to it. Overall, the morphine and ketamine dosages were increased to 564 mg/day and 140 mg/day, respectively, in 11 months until the patient expired. In this case, the high dosage of epidural morphine, 580 mg/day, was administered to control cancer pain without any severe adverse effects.

• The Korean Journal of Pain
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• v.11 no.1
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• pp.1-6
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• 1998

Background: The role of nitric oxide(NO) in analgesia from opioids is controversial. On the one hand, IV morphine analgesia is enhanced by IV injection of NO synthase inhibitors. On the other hand, IV morphine results in increased release of NO in the spinal cord. There have been no behavioral studies examining the interaction between IV morphine and intrathecal injection of drugs which affect NO synthesis. Method: Rats were prepared with chronic lumbar intrathecal catheters and were tested withdrawal latency on the hot plate after 3~5 days of surgery. Antinociception was determinined in response to a heat stimulus to the hind paw before and after IV injection of morphine, 2.5 mg/kg. Twenty minutes after morphine injection, rats received intrathecal injection of saline or the NO synthase inhibitors, L-NMMA or TRIM, the NO scavenger, PTIO, or the NO synthase substrate, L-Arginine. Intrathecal injections, separated by 15 min, were made in each rats and measurements were obtained every 5 min. Result: Mophine produced a 60~70% maximal antinociceptive response to a heat stimulus in all animals for 60 min in control experiments. Intrathecal injection of idazoxane decreased antinociception of IV morphine. The NO synthase inhibitors and the NO scavenger produced dose-dependent decreases in antinociceptive effect of morphine, whereas saline as a control group and L-Arginine as the NO substrate had no effect on antinociception of morphine. Conclusion: The present study supports the evidences that systemic morphine increase the nitrite in cerebrospinal fluid and dorsal horn. These data suggest that the synthesis of NO in the spinal cord may be important to the analgesic effect of IV morphine and increased NO in spinal cord has different action from the supraspinal NO.

• The Korean Journal of Pain
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• v.22 no.3
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• pp.199-205
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• 2009

Background: A major ingredient of green tea is epigallocatechin-3-gallate (EGCG), and this is known to have many beneficial effects for cancer prevention and also on the cardiovascular system and neurodegenerative diseases through its anti-oxidant, anti-angiogenic, anti-inflammatory, lipid-lowering and neuroprotective properties. Its actions on nociception and the spinal nervous system have been examined in only a few studies, and in these studies EGCG showed an antinociceptive effect on inflammatory and neuropathic pain, and a neuroprotective effect in motor neuron disease. This study was performed to investigate the effect of EGCG on acute thermal pain and the development of morphine tolerance at the spinal level. Methods: The experimental subjects were male Sprague-Dawley rats and the Hot-Box test was employed. A single or double-lumen intrathecal catheter was implanted at the lumbar enlargement for drug administration. An osmotic pump was used to infuse morphine for 7 days for induction of morphine tolerance. EGCG was injected repeatedly for 7 days at twice a day through the intrathecal catheter. Results: Intrathecal EGCG increased the paw withdrawal latency (PWL) after repeated administration for 7 days at twice a day, but this did not happen with administering on single bolus injection of EGCG. In addition, the antinociceptive effect of intrathecal morphine was not affected by co-administration with EGCG. A continuous 7-day infusion of morphine caused a significant decrease of the PWL in the control group (M + S, morphine plus saline). In contrast, intrathecal EGCG injection over 7 days blocked the decrease of the PWL in the experiment group (M + E, morphine plus EGCG). Conclusions: Intrathecal ECGC produced a weak antinociceptive effect for acute thermal pain, but it did not change the morphine's analgesic effect. However, the development of antinociceptive tolerance to morphine was attenuated by administering intrathecal EGCG.

• Journal of Pharmaceutical Investigation
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• v.33 no.2
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• pp.129-133
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• 2003

In order to evaluate the effects of vehicles and penetration enhancers on skin permeation of apomorphine, the skin permeation rates of apomorphine from vehicles of different composition were determined using Franz diffusion cells fitted with excised rat skins. Solubility of apomorphine in various solvents was investigated to select a vehicle suitable for the percutaneous absorption of apomorphine. The solvents used were propylene glycol (PG), $Transcutol^{\circledR},\;Labrasol^{\circledR},\;Labrafac hydro WL^{\circledR},\;Labrafil WL 2609 BS^{\circledR}$ and isopropyl alcohol. Even though permeation rates of apomorphine from each vehicle were low $(0.008-0.36\;{\mu}g/cm^2/hr)$, the combination of PG and $Labrafac^{\circledR}$ increased it significantly. The permeation rates of apomorphine from $PG/Labrafac^{\circledR}$ mixtures increased as the volume fraction of PG in the mixture increased. The maximum permeation rate of $18\;{\mu}g/cm^2/hr$ was achieved at 30% of PG, which decreased with further increase of PG fraction. A series of fatty acids, alcohols and monoterpenes were employed as penetration enhancers. Incorporation of each enhancer in the $PG/Labrafac^{\circledR}$ (30:70) mixture at the level of 10% improved the skin permeation significantly. The highest permeation rate, $117\;{\mu}g/cm^2/hr$, was attained with myristic acid.

• The Korean Journal of Pain
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• v.5 no.1
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• pp.29-36
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• 1992

This study was objected to evaluate clinical progressions about both the degree of pain relief and the occurrence of morphine tolerance while the epidural analgesia with low dose of morphine, bupivacaine and antidepressant continued repeatedly at every 5 day intervals of the constant-rate infusion(0.5 ml/hr, 60 ml capacity). The subjects were divided to 56 cancer and 36 non-cancer patients who failed to respond to palliative treatments. Before the relief of pain, the pain severity was moderate(10%) and severe(90%). The dose escalation of morphine noted to 11(20%)patients in cancer pain and to one(5%) case only in non-cancer. During the epidural analgesia, the effect of pain relief was moderate(11%) and good(89%). It suggest that the morphine tolerance may be reduced to some degree such as an initial minimum dose of epidural morphine with local anesthetic and antidepressant should be adjusted on an individual basis using the constant-rate infusor, even though rapid dose escalation occurrs in some patients who the diseases progress over a short period of time.

• The Korean Journal of Pain
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• v.10 no.2
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• pp.170-178
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• 1997

Background: The analgesic efficacy and safety of propacetamol, an injectable prodrug of acetoaminophen, in combination with intravenous morphine PCA were studied in 40 patients after gynecological surgery requiring lower abdominal incision. Methods: Using a double-blind, randomized, parallel-group design, the effects of four(every 6 hr) intravenous injections of 2 g propacetamol(=1 g acetoaminophen) were compared with four injections of placebo(PL) immediately after surgery. Efficacy of cumulative dose of morphine and number of boluses requested was assessed over 24 hours by automated recording on the PCA device. It was assessed on pain scores rated on a ten-point verbal scale along with vital signs, $K^+$, glucose, BUN, creatinine, PT and PTT were measured along with stress hormones(epinephrine, norepinephrine and cortisol). Results: There were no differences in demographic data between two groups. Propacetamol group demonstrated approximately 21% morphine sparing effect compared to placebo group($33.1{\pm}10.4$ mg vs $41.4{\pm}8.0$ mg). No significant differences noted in $K^+$, glucose, BUN, Creatinine, PT and PTT levels. There were significant increases in norepinephrine and cortisol in placebo group postoperatively, compared to preoperative values. At the same time, propacetamol group also showed significant changes in these hormones. Both group revealed high degree of patient satisfaction. Conclusion: Propacetamol showed significant morphine sparing effect to some degree. Side effects were much less in propacetamol group with subsequently high patient satisfaction. The secretion of stress hormone were not blocked by postoperative propacetamol injections. Authors concluded that propacetamol should be considered as an excellent adjuvant analgesics in postoperative pain control in opioid patient controlled analgesia.

• The Korean Journal of Pain
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• v.6 no.2
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• pp.220-223
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• 1993

Administration of local anesthetics or morphine through epidural space has the effect of curbing postoperative increases in endocrine hormone. Other benefits include improving metabolic reaction and eliminating postoperative pain. However, repeated administration of local anesthetics through epidural space causes tachyphylaxis, and the unstable blockade of sensory nerve resulting in insufficient analgesia. Morphine has excellent postoperative analgesic effect, but complications including: itching, nausea, vomiting, urinary retention and respiratory depression may be associated with its administration. Sixty patients that fall into the category of ASA class I and II were randomly selected for the purpose of the experiment. Thirty patients were give 4 mg of morphine and the rest, 4 mg of morphine plus 80 ml of 0.25% bupivacaine administered through epidural space with the Baxter infuser. Analgesic effect was satisfactory in both groups. On the day of operation, the effect was stronger in group I (P<0.05) and on postoperative second day, group II showed better analgesic effect (P < 0.05). Group II had more patients who complained of itching (P < 0.05). Other complications were statistically insignificant. The findings indicate that administration of morphine through epidural space for postoperative pain management is an effective procedure. Baxter infuser was found to be very instrumental in pain control while reducing the chance of complications.