PURPOSE: Intrathecal morphine pump (ITMP) infusion therapy is efficient in managing malignant and nonmalignant chronic pain refractory to standard treatment. However, the high cost of an ITMP is the greatest barrier for starting a patient on ITMP infusion therapy. Using the revised Korean reimbursement guidelines, we investigated the cost effectiveness of ITMP infusion therapy and conducted a patient survey. MATERIALS AND METHODS: A retrospective chart review of 12 patients who underwent ITMP implantation was performed. Morphine dose escalation rates were calculated, and numeric rating scale (NRS) scores were compared before and after ITMP implantation. We surveyed patients who were already using an ITMP as well as those who were candidates for an ITMP. All survey data were collected through in-person interviews over 3 months. Data on the cost of medical treatment were collected and projected over time. RESULTS: The NRS score decreased during the follow-up period. The median morphine dose increased by 36.9% over the first year, and the median time required to reach a financial break-even point was 24.2 months. Patients were more satisfied with the efficacy of ITMP infusion therapy than with conventional therapy. The expected cost of ITMP implantation was KRW 4000000-5000000 in more than half of ITMP candidates scheduled to undergo implantation. CONCLUSION: The high cost of initiating ITMP infusion therapy is challenging; however, the present results may encourage more patients to consider ITMP therapy.
Adult ; Aged ; Analgesics, Opioid/*administration & dosage/economics/therapeutic use ; Chronic Pain/*drug therapy ; Cost-Benefit Analysis ; Female ; Humans ; Infusion Pumps, Implantable/*economics ; Injections, Spinal ; Male ; Middle Aged ; Morphine/*administration & dosage/economics/therapeutic use ; Pain Management/*methods/trends ; Patient Satisfaction ; Republic of Korea ; Retrospective Studies ; Surveys and Questionnaires ; Treatment Outcome

BACKGROUND: Postoperative pain relief can be achieved with various modalities. However, there are only few reports that have analyzed postoperative analgesic techniques in total hip arthroplasty patients. The aim of this retrospective study was to compare the postoperative outcomes of three different analgesic techniques after total hip arthroplasty. METHODS: We retrospectively reviewed the influence of three analgesic techniques on postoperative rehabilitation after total hip arthroplasty in 90 patients divided into three groups (n = 30 patients per group). Postoperative analgesia consisted of continuous epidural analgesia (Epi group), patient-controlled analgesia with morphine (PCA group), or a continuous femoral nerve block (CFNB group). We measured the following parameters relating to postoperative outcome: visual analog scale scores, the use of supplemental analgesia, side effects, length of the hospital stay, plasma D-dimer levels, and the Harris hip score. RESULTS: Each group had low pain scores with no significant differences between the groups. The PCA group had a lower frequency of supplemental analgesia use compared to the Epi and CFNB groups. Side effects (nausea/vomiting, inappetence) and day 7 D-dimer levels were significantly lower in the CFNB group (p < 0.05). There were no significant differences between the groups in terms of the length of the hospital stay or the Harris hip score. CONCLUSIONS: Although there were no clinically significant differences in outcomes between the three groups, the CFNB provided good pain relief which was equal to that of the other analgesics with fewer side effects and lower D-dimer levels in hospitalized patients following total hip arthroplasty.
Adult ; Aged ; Aged, 80 and over ; *Analgesia, Epidural/methods ; *Analgesia, Patient-Controlled ; Analgesics, Opioid/*administration & dosage ; *Arthroplasty, Replacement, Hip ; Female ; *Femoral Nerve ; Fibrin Fibrinogen Degradation Products/analysis ; Humans ; Length of Stay ; Male ; Middle Aged ; Morphine/*administration & dosage ; *Nerve Block/methods ; Pain, Postoperative/*prevention & control ; Retrospective Studies ; Treatment Outcome

The purpose of the present study is to analyze the relationship between the telemetry electroencephalogram (EEG) changes of the prelimbic (PL) cortex and the drug-seeking behavior of morphine-induced conditioned place preference (CPP) rats by using the wavelet packet extraction and entropy measurement. The recording electrode was stereotactically implanted into the PL cortex of rats. The animals were then divided randomly into operation-only control and morphine-induced CPP groups, respectively. A CPP video system in combination with an EEG wireless telemetry device was used for recording EEG of PL cortex when the rats shuttled between black-white or white-black chambers. The telemetry recorded EEGs were analyzed by wavelet packet extraction, Welch power spectrum estimate, normalized amplitude and Shannon entropy algorithm. The results showed that, compared with operation-only control group, the left PL cortex's EEG of morphine-induced CPP group during black-white chamber shuttling exhibited the following changes: (1) the amplitude of average EEG for each frequency bands extracted by wavelet packet was reduced; (2) the Welch power intensity was increased significantly in 10-50 Hz EEG band (P < 0.01 or P < 0.05); (3) Shannon entropy was increased in β, γ₁, and γ₂waves of the EEG (P < 0.01 or P < 0.05); and (4) the average information entropy was reduced (P < 0.01). The results suggest that above mentioned EEG changes in morphine-induced CPP group rat may be related to animals' drug-seeking motivation and behavior launching.
Animals ; Conditioning (Psychology) ; Drug-Seeking Behavior ; Electroencephalography ; Entropy ; Morphine ; pharmacology ; Prefrontal Cortex ; drug effects ; Rats ; Telemetry ; Wavelet Analysis

BACKGROUNDOpioid switching is a therapeutic maneuver to improve analgesic response and/or reduce adverse side effects although the underlying mechanisms remain unknown. The µ-opioid receptor (MOR) has an important role in mediating the actions of morphine and other analgesic agents. This study is aimed at exploring the changes of MOR in the periaqueductal gray (PAG) in rats when morphine is substituted for equianalgesic fentanyl.

METHODSForty rats were randomly assigned to five treatment groups: 7 days normal saline group (N group), 7 days fentanyl group (F group), 7 days morphine group (M group), 7 days morphine and 7 days fentanyl-switching group (MF group), and 14 days morphine group (MM group). Rats repeatedly received subcutaneous injections of morphine sulfate (10 mg/kg) or equianalgesic fentanyl sulfate (0.1 mg/kg) twice daily. Rats' antinociceptive response to thermal pain was evaluated by the tail flick latency assay. MOR mRNA and protein expression in the PAG were measured using RT-PCR and Western blotting analyses respectively.

RESULTSThis study showed that after morphine was substituted with fentanyl on day 8, the tail flick latency (TFL) increased from (3.9 ± 0.4) seconds to (11.4 ± 0.4) seconds. The results also demonstrated that both MOR mRNA and protein expression in the PAG of rats in the MF group were less than that in the M group (P < 0.05) but more than that in MM group (P < 0.05).

CONCLUSIONSEquianalgesic fentanyl was still antinociceptive effective in rats with morphine tolerance, which may be due to the switching from morphine to fentanyl attenuating the decline of MOR expression in the PAG of rats.

Analgesics, Opioid ; pharmacology ; Animals ; Drug Tolerance ; Fentanyl ; pharmacology ; Male ; Morphine ; pharmacology ; Periaqueductal Gray ; chemistry ; RNA, Messenger ; analysis ; Rats ; Rats, Wistar ; Receptors, Opioid, mu ; analysis ; genetics

Opioids are the one of the most commonly used drugs to control cancer pain all over the world. But, we should not overlook the potential risk of opioid intoxication because they have well-known detrimental side effects. The opioid intoxication can be diagnosed thorough various clinical manifestations. The altered mental status, respiratory depression, and miosis is very representative clinical features although these symptoms don't always appear together. Unfortunately the opioid-toxidrome can be varied. A 42 years old man came to our emergency room after taking about 900 mg morphine sulfate per oral. He was nearly alert and his respiration was normal. Even though his symptoms didn't deteriorated clinically, serial arterial blood gas analysis showed increase in PaCO2. So we decided to use intravenous naloxone. Soon, he was fully awaked and his pupils size was increased. After a continuous infusion of intravenous naloxone for 2 hours, PaCO2 decreased to normal range and his pupil size also returned to normal after 12 hours. Though the levels of serum amylase and lipase increased slightly, his pancreas was normal according to the abdominal computed tomography. He had nausea, vomit, and whole body itching after naloxone continuous infusion, but conservatively treated. We stopped the continuos infusion after 1 day because his laboratory results and physical examinations showed normal. As this case shows, it is very important to prescribe naloxone initially. If you suspect opioid intoxication, we recommend the initial use of naloxone even though a patient has atypical clinical features. In addition, we suggest intranasal administration of naloxone as safe and effective alternative and it's necessary to consider nalmefene that has a longer duration for opioid intoxication.
Administration, Intranasal ; Amylases ; Analgesics, Opioid ; Blood Gas Analysis ; Emergencies ; Humans ; Lipase ; Miosis ; Morphine ; Naloxone ; Naltrexone ; Nausea ; Pancreas ; Physical Examination ; Porphyrins ; Pruritus ; Pupil ; Reference Values ; Respiration ; Respiratory Insufficiency

Recent studies have shown that astrocytes play important roles in ATP degradation and adenosine (a well known analgesic molecule) generation, which are closely related to pain signaling pathway. The aim of this study was to investigate whether morphine, a well known analgesic drug, could affect the speeds of ATP enzymolysis and adenosine generation in rat astrocytes. Intracellular calcium concentration ([Ca(2+)](i)) of astrocyte was measured by flow cytometry, and the time points that morphine exerted notable effects were determined for subsequent experiments. Cultured astrocytes were pre-incubated with morphine (1 μmol/L) and then were incubated with substrates, ATP and AMP, for 30 min. The speeds of ATP enzymolysis and adenosine generation were measured by high performance liquid chromatography (HPLC). The results showed that both 1.5 and 48 h of morphine pre-incubation induced maximal ATP enzymolysis speed in astrocytes among all the time points, and there was no statistical difference of ATP enzymolysis speed between morphine treatments for 1.5 and 48 h. As to adenosine, morphine pre-incubation for 1.5 h statistically increased adenosine generation, which was degraded from AMP, in cultured astrocytes compared with control group. However, no difference of adenosine generation was observed after 48 h of morphine pre-incubation. These results indicate that treatment of morphine in vitro dynamically changes the concentrations of ATP and adenosine in extracellular milieu of astrocytic cells. In addition, astrocyte can be regarded as at least one of the target cells of morphine to induce changes of ATP and adenosine levels in central nervous system.
Adenosine ; biosynthesis ; Adenosine Triphosphate ; metabolism ; Analgesics, Opioid ; pharmacology ; Animals ; Animals, Newborn ; Astrocytes ; cytology ; drug effects ; metabolism ; Calcium ; analysis ; metabolism ; Cells, Cultured ; Cerebral Cortex ; cytology ; Morphine ; pharmacology ; Rats ; Rats, Sprague-Dawley

The paper is to establish a method for simultaneous determination of 5 kinds of alkaloids in ephedra and poppy which are in Kechuanning tablets. Solid-phase extraction (SPE) was adopted in pretreatment, and a UPLC method with 2 different wavelengths had been developed: 210 nm for the detection of morphine, codeine phosphate, ephedrine hydrochloride and pseudoephedrine hydrochloride, and 251 nm for papaverine hydrochloride. The column used was Acquity UPLC BEH C18 (100 mm x 2.1 mm ID, 1.7 microm) with linear gradient elution using acetonitrile and 0.1% phosphoric acid. The flow rate was 0.4 mL.min-1, and the column temperature was 30 degrees C. The linear response range was 0.375 0 - 12.50 microg.mL-1 for morphine, 0.064 32 - 2.144 microg.mL-1 for codeine phosphate, 0.030 06 - 1.002 microg.mL-1 for papaverine hydrochloride, 1.126 - 37.52 microg.mL-1 for ephedrine hydrochloride, 0.287 8 - 9.592 microg.mL-1 for pseudoephedrine hydrochloride (r = 0.999 7). The average recoveries of these compounds were 99.26%, 100.6%, 95.29%, 100.1% and 97.48%, respectively. This is a more reasonable and credible method of quality control for Kechuanning tablets.
Alkaloids ; analysis ; Chromatography, High Pressure Liquid ; Codeine ; analysis ; Drugs, Chinese Herbal ; administration & dosage ; chemistry ; isolation & purification ; Ephedra ; chemistry ; Ephedrine ; analysis ; Morphine ; analysis ; Papaver ; chemistry ; Papaverine ; analysis ; Plants, Medicinal ; chemistry ; Pseudoephedrine ; analysis ; Quality Control ; Solid Phase Extraction ; Tablets

The paper reports the establishment of a liquid chromatography-tandem mass spectrometry (LC-MS/MS) for simultaneous analysis of 11 opiates in hair samples, and the study of presence of opiates in the hair of active heroin addicts. About 20 mg of decontaminated and pulverized hair sample was hydrolyzed with buffer solution for 30 min, in the presence of morphine-d3 and acetylmorphine-d6 used as internal standards, and then extracted with the mixture of dichlormethane and isopropanol, separated by the Allure PFP propyl column with a mobile phase consisting of acetonitrile and 20 mmol L(-1) ammonium acetate buffer, and then analyzed by LC-MS/MS. Multiple reaction monitoring (MRM) mode was used to analyze 11 opiates. Eleven opiates showed a fairly good linearity over the corresponding range (r > 0.996 0). The detection limits were less than 0.05 ng mg(-1). The recoveries were between 47.2% and 110%, and the deviations of intra- and inter-day precision were less than 14%. Heroin, acetylmorphine, morphine, codeine, acetylcodeine and hydrocodone were detected in hair samples of 21 herion addicts. The developed method shows high sensitivity and selectivity, and is suitable for the simultaneous analysis of 11 opiates in hair samples and identify legal and illegal use of opiates.
Analgesics, Opioid ; analysis ; Chromatography, Liquid ; methods ; Codeine ; analogs & derivatives ; analysis ; Hair ; chemistry ; Heroin ; analysis ; Humans ; Hydrocodone ; analysis ; Limit of Detection ; Morphine ; analysis ; Morphine Derivatives ; analysis ; Sensitivity and Specificity ; Substance Abuse Detection ; methods ; Tandem Mass Spectrometry ; methods

OBJECTIVE: To analyze the morphine rabbit myocardium with matrix-assisted laser desorption/ ionization time-of-flight mass spectrometry (MALDI-TOF-MS). METHODS: Six New Zealand white rabbits were randomly assigned to a control group (Group C) and a morphine group (Group M). Group C were pretreated with bolus injection of saline 1 mL/kg. Group M were pretreated with bolus injection of morphine 3 mg/kg. The myocardium tissue proteins of the rabbits 24 hours after the injection of morphine or saline preconditioned were extracted and separated by two dimensional gel electrophoresis(2-DE), and the images were analyzed and different proteins were found. Some of the different proteins were determined with MALDI-TOF-MS. RESULTS: There were 51 protein spots that displayed quantitative changes in expression (P < 0.05), 15 protein spots were chosen for MS analysis, and 8 proteins were preliminarily identified.They were aldose reductase, zinc finger protein 312, src related tyrosine kinase, carbonic anhydrase 12 precursor, electron transfer flavoprotein beta-subunit, glyceraldehyde-3-phosphate dehydrogenase, tumor necrosis factor ligand superfamily member 11 and transmembrane emp24 domain-containing protein. CONCLUSION These proteins may be involved in the cardioprotection of morphine preconditioning.
Animals ; Electrophoresis, Gel, Two-Dimensional ; Female ; Ischemic Preconditioning, Myocardial ; methods ; Male ; Morphine ; pharmacology ; Myocardial Reperfusion Injury ; metabolism ; Myocardium ; metabolism ; Proteome ; analysis ; Proteomics ; methods ; Rabbits ; Random Allocation ; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization ; methods

BACKGROUND: Additive opioids in spinal anesthesia of cesarean section decrease the dose of local anesthetics and increase the quality of anesthesia. There were comparative studies about morphine, fentanyl, and sufentanil as an additive opioid in spinal anesthesia of cesarean section, but few studies about alfentanil. In this study we compared the effect of alfentanil with fentanyl as an additive opioid in spinal anesthesia for cesarean section. METHODS: Sixty nine pregnant women, American Society of Anesthesiologist (ASA) I-II, who were scheduled for elective cesarean section under spinal anesthesia, were randomly allocated into two groups: group F received 8 mg (1.6 ml) of bupivacaine and 15microg of fentanyl (0.3 ml) intrathecally, and group A received 8 mg of bupivacaine and 150microg of alfentanil (0.3 ml). Sensory block defined by pin-prick, intraoperative patient satisfaction for analgesia by visual analogue scale (VAS), blood pressure, and side effects were assessed. Apgar score and umbilical arterial blood gas analysis were also assessed. RESULTS: The analgesic effect of alfentanil was as good as fentanyl and VAS for satisfaction was 97.1 +/- 7.6 and 96.5 +/- 8.0 each. Time to achieve anesthetic level of T6 (6.2 vs 6.7 min), maximal block level (T3.7 vs T3.8), lowest blood pressure during the operation (60.0 vs 61.0 mmHg), duration of analgesia (77.2 vs 70.0 min), and fetal assessment were not different from those of group F, either. The incidence of nausea during operation was 48.6% in group F and 26.4% in group A (P = 0.14). CONCLUSIONS: The addition of alfentanil is comparable to fentanyl in analgesia, maternal and fetal effects in spinal anesthesia for cesarean section.
Alfentanil ; Analgesia ; Analgesics, Opioid ; Anesthesia ; Anesthesia, Spinal ; Anesthetics, Local ; Apgar Score ; Blood Gas Analysis ; Blood Pressure ; Bupivacaine ; Cesarean Section ; Female ; Fentanyl ; Humans ; Incidence ; Morphine ; Nausea ; Patient Satisfaction ; Pregnancy ; Pregnant Women ; Sufentanil