BACKGROUND/AIMS: The influence of external factors such as opioids and alcohol has been extensively investigated for various segments of the gastrointestinal tract. However, the association between their use and the development of esophagogastric junction outflow obstruction disorders (EGJOODs) is unknown. Therefore, the aim of this study is to analyze prevalence and clinical relevance of opioids and alcohol intake in patients with EGJOODs. METHODS: In this single-center, retrospective study, we reviewed clinical and pharmacological data of 375 consecutive patients who had undergone high resolution impedance manometry for EGJOODs. EGJOODs were classified according to the Chicago classification version 3.0 and to recently published normal values for test meals. Demographics, manometric data, and symptoms were compared between different groups using Pearson's chi-squared test, Fisher's exact test, and multivariate analysis. A P < 0.05 was considered significant. RESULTS: EGJOOD was found in 30.7% (115/375) of all analyzed patients. The prevalence of opioids (14.8% vs 4.2%, P = 0.026) was significantly higher in patients with EGJOODs compared to patients without EGJOODs. Additionally, excessive alcohol consumption (12.2% vs 3.5%, P = 0.011) was associated with EGJOODs. Excessive alcohol consumption was especially frequent in the non-achalasia esophagogastric junction outflow obstruction subgroup (16.2%) and opioid use in the achalasia type III subgroup (20.0%). CONCLUSIONS: We found a significant association between EGJOODs and opioid as well as excessive alcohol consumption. This underlines the importance of detailed history taking regarding medication and ethanol consumption in patients with dysphagia. Further prospective studies on mechanisms undelaying esophagogastric junction dysfunction due to opioids or alcohol are warranted.
Alcohol Drinking ; Analgesics, Opioid ; Classification ; Deglutition Disorders ; Demography ; Electric Impedance ; Esophageal Achalasia ; Esophagogastric Junction ; Ethanol ; Gastrointestinal Tract ; Humans ; Manometry ; Meals ; Multivariate Analysis ; Prevalence ; Prospective Studies ; Reference Values ; Retrospective Studies

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

BACKGROUND/AIMS: Little is known about the efficacy of low-dose transdermal fentanyl (TDF) patches in opioid-naive patients with moderate-to-severe cancer pain. METHODS: This study had an open-label, prospective design, and was conducted between April 2007 and February 2009 in seven tertiary cancer hospitals; 98 patients were enrolled. TDF was started using a low-dose formulation (12.5 microg/hr), and the dose was adjusted according to the clinical situation of individual patients. Pain intensity, the TDF doses used, and adverse events (AEs) were monitored over 4 weeks. Data were analyzed using the intent-to-treat and per-protocol principles. RESULTS: Of the 98 patients enrolled, 64 (65%) completed the study. The median pain intensity decreased from 6.0 to 3.0 (p < 0.001) at the follow-up visit. The efficacy of low-dose TDF on pain relief was consistent across groups separated according to gender (p < 0.001), age (p < 0.001), metastasis (p < 0.001), previous treatment (p < 0.001), and baseline pain intensity (p < 0.001). The decrease in pain intensity was significantly greater in the severe group compared with the moderate group (mean +/- SD, 5.10 +/- 2.48 vs. 2.48 +/- 1.56; p < 0.001). TDF dose (27.8 microg/hr vs. 24.8 microg/hr, p = 0.423) and the mean treatment time (7.5 days vs. 7.9 days, p = 0.740) required for pain control were not different between the two pain-intensity groups. Patients had AEs of only mild or moderate intensity; among these, nausea (38%) was the most common, followed by vomiting (22%) and somnolence (22%). CONCLUSIONS: Low-dose TDF was an effective treatment for patients with cancer pain of moderate-to-severe intensity. Further randomized trials assessing the efficacy of TDF for severe pain and/or optimal starting doses are warranted.
Administration, Cutaneous ; Adult ; Aged ; Aged, 80 and over ; Analgesics, Opioid/*administration & dosage/adverse effects ; Female ; Fentanyl/*administration & dosage/adverse effects ; Humans ; Intention to Treat Analysis ; Male ; Middle Aged ; Neoplasms/*complications ; Pain/diagnosis/*drug therapy/etiology ; Pain Measurement ; Prospective Studies ; Republic of Korea ; Severity of Illness Index ; Tertiary Care Centers ; Time Factors ; Transdermal Patch ; Treatment Outcome

PURPOSE: Postoperative ileus (POI) is common following bowel resection for radical cystectomy with ileal conduit (RCIC). We investigated perioperative factors associated with prolonged POI following RCIC, with specific focus on opioid-based analgesic dosage. MATERIALS AND METHODS: From March 2007 to January 2013, 78 open RCICs and 26 robot-assisted RCICs performed for bladder carcinoma were identified with adjustment for age, gender, American Society of Anesthesiologists grade, and body mass index (BMI). Perioperative records including operative time, intraoperative fluid excess, estimated blood loss, lymph node yield, and opioid analgesic dose were obtained to assess their associations with time to passage of flatus, tolerable oral diet, and length of hospital stay (LOS). Prior to general anaesthesia, patients received epidural patient-controlled analgesia (PCA) consisted of fentanyl with its dose adjusted for BMI. Postoperatively, single intravenous injections of tramadol were applied according to patient desire. RESULTS: Multivariate analyses revealed cumulative dosages of both PCA fentanyl and tramadol injections as independent predictors of POI. According to surgical modality, linear regression analyses revealed cumulative dosages of PCA fentanyl and tramadol injections to be positively associated with time to first passage of flatus, tolerable diet, and LOS in the open RCIC group. In the robot-assisted RCIC group, only tramadol dose was associated with time to flatus and tolerable diet. Compared to open RCIC, robot-assisted RCIC yielded shorter days to diet and LOS; however, it failed to shorten days to first flatus. CONCLUSION: Reducing opioid-based analgesics shortens the duration of POI. The utilization of the robotic system may confer additional benefit.
Aged ; Analgesics, Opioid/*administration & dosage/therapeutic use ; Carcinoma/*surgery ; Cystectomy/*adverse effects ; Dose-Response Relationship, Drug ; Female ; Humans ; Ileus/*epidemiology ; Length of Stay ; Linear Models ; Male ; Middle Aged ; Multivariate Analysis ; Robotic Surgical Procedures/adverse effects ; Time Factors ; Tramadol/*administration & dosage/therapeutic use ; Treatment Outcome ; Urinary Bladder Neoplasms/*surgery ; Urinary Diversion/*adverse effects

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

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

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

INTRODUCTIONConcerns about the life shortening effect of opioids is a well known fact in the medical world when considering administration of these drugs for symptom alleviation at end of life. This study described the patterns of opioid use among cancer patients referred to a hospital-based specialist palliative care service for symptom management. This study also examined whether opioid use among terminally ill cancer patients during the last 2 days of life had any influence on survival.

MATERIALS AND METHODSA retrospective review of case notes of patients who were diagnosed with terminal cancer and had passed away in a 95-bedded oncology ward between September 2006 and September 2007 was conducted. Data were collected on patients' characteristics and patterns of opioid use including opioid doses and dose changes at 48 hours and 24 hours before death.

RESULTSThere were 238 patients who received specialist palliative care, of whom 132 (55.5%) were females. At 48 hours and 24 hours before death, 184 (77.3%) patients and 187 (78.6%) patients had received opioids, respectively. The median daily doses at 48 hours and 24 hours were 48 mg and 57 mg oral morphine equivalent doses (OME), respectively. Indications for opioid use were pain (41.1%), dyspnoea, (29.1%) and both dyspnoea and pain (30.8%). In the fi nal 24 hours, 22.3% patients had a reduction in their mean opioid dose while 22.7% required an increase in their mean opioid dose. Increased age was associated with decreasing opioid doses (P = 0.003). Patients with spinal metastases required higher doses of opioids (P = 0.03) while those with lung metastases required lower doses (P = 0.011). Survival analysis using Kaplan-Meier survival curve revealed no significant survival difference between those who were on opioids and those who were not. Log rank test (Mantel-Cox) (P = 0.69).

CONCLUSIONOur results showed that opioids are safe medications for symptom alleviation in terminally ill cancer patients during the last days of life and have no deleterious influence on survival.

Adolescent ; Adult ; Aged ; Aged, 80 and over ; Analgesics, Opioid ; administration & dosage ; therapeutic use ; Female ; Humans ; Male ; Medical Audit ; Middle Aged ; Neoplasms ; physiopathology ; Retrospective Studies ; Survival Analysis ; Terminal Care ; Young Adult