BACKGROUND: Ischemic insult during operation could cause ischemic-reperfusion injuries in brain and memory impairments. Total intravenous anesthesia (TIVA) is preferred in brain surgery to promote the use of motor evoked potential monitoring and the use of opioids is common in TIVA. However there were few studies about ischemic protective effect of opioids to astrocytes. METHODS: We used astrocytes, which were derived from human brain. We divided groups by conditioning period; i) pre-culture, ii) post-culture, or iii) pre + post-culture. All groups were treated 100 nM hydromorphone. We measured reactive oxygen species (ROS) by flow cytometry with 2',7'-dichloroflurorescin diacetate. Then ROS in astrocytes which treated by opioid receptor antagonist were measured after treating 100 nM hydromorphone. RESULTS: ROS was reduced in hydromorphone treated group, as compared to the control group (only tert-butyl hydroperoxide [TBH] treated). There was no difference in pre-conditioned group and post-conditioned group. However, ROS was much more reduced in pre + post-conditioned group compared to pre-conditioned only or post-conditioned only group. Furthermore each selective micro-, delta- and kappa-opioid receptor antagonists partially negated the effect of hydromorphone. CONCLUSIONS: This study provides evidence that hydromorphone has both preconditioning and postconditioning effects on TBH-induced oxidative stress. Furthermore we proved each micro-, delta- and kappa-opioid receptor relates to protective mechanism of hydromorphone to astrocytes.
Analgesics, Opioid ; Anesthesia, Intravenous ; Astrocytes ; Brain ; Brain Ischemia* ; Evoked Potentials, Motor ; Flow Cytometry ; Humans ; Hydromorphone* ; Memory ; Oxidative Stress ; Reactive Oxygen Species ; Receptors, Opioid ; tert-Butylhydroperoxide

Extended-release osmotic extended-release oral delivery system (OROS) hydromorphone is a strong synthetic opioid designed to maintain a constant blood concentration by once daily dosing. The objective of this observational study was to investigate the clinical usefulness of OROS hydromorphone in patients with cancer pain of moderate to severe intensity. Patients with cancer pain who required strong opioids were administered with OROS hydromorphone for 4 weeks. We assessed changes in pain intensity using a numerical rating scale (NRS) as well as levels of sleep disturbance, breakthrough pain, end-of-dose failure, patient satisfaction, and overall assessment of drug effectiveness based on investigator evaluation. Of the 648 enrolled patients, 553 patients were included in the full analysis set. The mean pain intensity was significantly decreased from the NRS value of 5.07 ± 1.99 to 2.75 ± 1.94 (mean % change of 42.13 ± 46.53, P < 0.001). The degree of sleep disturbance significantly improved (mean NRS change of 1.61 ± 2.57, P < 0.001), and the incidence of breakthrough pain was significantly decreased (mean NRS change of 1.22 ± 2.30, P < 0.001). The experience of end-of-dose failure also significantly decreased from 4.60 ± 1.75 to 3.93 ± 1.70, P = 0.007). The patient satisfaction rate was 72.7%, and 72.9% of investigators evaluated the study drug as effective. OROS hydromorphone was an effective and tolerable agent for cancer pain management. It effectively lowered pain intensity as well as improved sleep disturbance, breakthrough pain, and end-of-dose failure (Identifier: NCT 01273454).
Analgesics, Opioid ; Breakthrough Pain ; Chronic Pain ; Humans ; Hydromorphone* ; Incidence ; Observational Study ; Pain Management ; Patient Satisfaction ; Research Personnel

Breakthrough cancer pain is a transient exacerbation of pain that occurs despite relatively well controlled background pain with around-the-clock analgesia. It is highly prevalent in patients with cancer pain, with an overall prevalence of 70~90%. Breakthrough cancer pain has several negative effects on quality of life, including a decrease in functional status and social relationship, and higher incidence of anxiety/depression. It also places a detrimental burden on their families, society, and the healthcare system. According to the pathogenic mechanism, breakthrough cancer pain is classified into two categories: idiopathic (or spontaneous) pain and incident pain. Episodes of breakthrough cancer pain have typical characteristics, including rapid onset (5~10 min), severe intensity, and short duration (30~60 min). However, there are some variations in timing and severity of pain among patients and episodes. Therefore, a thorough assessment of pain episodes is needed and management plan must be individualized to provide optimal treatment. Several immediate-release formulations such as oxycodone, morphine, and hydromorphone are widely used despite relatively slow onset of action. Recent studies have shown that transmucosal fentanyl preparations were effective for faster control of breakthrough pain. We hope to improve management of breakthrough cancer pain with more efficient analgesics in line with currently available evidence.
Analgesia ; Analgesics ; Breakthrough Pain ; Delivery of Health Care ; Fentanyl ; Hope ; Humans ; Hydromorphone ; Incidence ; Morphine ; Oxycodone ; Prevalence ; Quality of Life

BACKGROUND: Preemptive analgesia is known to decrease the sensitization of the central nervous system and reduce subsequent amplification of nociceptive stimuli. We investigated whether preemptive thoracic epidural analgesia (TEA) demonstrated intraoperative and postoperative short and long term clinical advantages. METHODS: Thirty patients scheduled for open thoracotomy were randomly allocated to one of two groups to receive continuous TEA (0.15% bupivacaine and 8 microg/ml hydromorphone) either before surgical incision (preemptive group) or at the end of the operation (nonpreemptive group). Incidence of hypotension during surgery was recorded. Numerical rating scales (NRS) and the incidence of side effects such as nausea, pruritus, sedation, hypotension, and respiratory depression were recorded at 2, 6, 24, and 48 hours postoperatively. Pulmonary function test (PFT) was performed before, 24 and 48 hours after the operation. Persistence of pain control was investigated at 6 months postoperatively. RESULTS: The NRS score, side effects, and PFT changes were comparable between the two groups. TEA and intravenous rescue morphine consumed at 2, 6, 24, and 48 hours postoperatively were not different between the two groups. During surgery, the incidence of hypotension was significantly higher in the preemptive group (P = 0.027). At 6-month follow up, two patients in the nonpreemptive group complained of persistent pain at wound and none in the preemptive group. CONCLUSIONS: Preemptive TEA with hydromorphone and bupivacaine during surgery may cause unnecessary intraoperative hypotension without a prominent advantage in reducing acute or chronic pain or enhancing pulmonary function after thoracotomy. The advantageous concept of preemptive TEA may be dubious and may not provide perioperative clinical benefits.
Analgesia ; Analgesia, Epidural* ; Bupivacaine* ; Central Nervous System ; Chronic Pain ; Follow-Up Studies ; Humans ; Hydromorphone* ; Hypotension ; Incidence ; Lung* ; Morphine ; Nausea ; Pruritus ; Respiratory Function Tests ; Respiratory Insufficiency ; Tea ; Thoracotomy* ; Weights and Measures ; Wounds and Injuries

BACKGROUND: Spinal opioid administration is an excellent option to separate the desirable analgesic effects of opioids from their expected dose-limiting side effects to improve postoperative analgesia. Therefore, physicians must better identify either specific opioids or adequate doses and routes of administration that result in a mainly spinal site of action rather than a cerebral analgesic one. METHODS: The purpose of this topical review is to describe current available clinical evidence to determine what opioids reach high enough concentrations to produce spinally selective analgesia when given by epidural or intrathecal routes and also to make recommendations regarding their rational and safety use for the best management of postoperative pain. To this end, a search of Medline/Embase was conducted to identify all articles published up to December 2013 on this topic. RESULTS: Recent advances in spinal opioid bioavailability, based on both animals and humans trials support the theory that spinal opioid bioavailability is inversely proportional to the drug lipid solubility, which is higher in hydrophilic opioids like morphine, diamorphine and hydromorphone than lipophilic ones like alfentanil, fentanyl and sufentanil. CONCLUSIONS: Results obtained from meta-analyses of RTCs is considered to be the 'highest' level and support their use. However, it's a fact that meta-analyses based on studies about treatment of postoperative pain should explore clinical surgery heterogeneity to improve patient's outcome. This observation forces physicians to use of a specific procedure surgical-based practical guideline. A vigilance protocol is also needed to achieve a good postoperative analgesia in terms of efficacy and security.
Alfentanil ; Analgesia ; Analgesics, Opioid ; Animals ; Biological Availability ; Fentanyl ; Heroin ; Humans ; Hydromorphone ; Morphine ; Pain, Postoperative* ; Population Characteristics ; Solubility ; Sufentanil

No abstract available.
Colonic Neoplasms* ; Humans ; Hydromorphone* ; Intercellular Adhesion Molecule-1*

BACKGROUND: Nuss surgery is preferred in pectus excavatum repair because this procedure produces excellent cosmetic results and prevents postoperative distressed pulmonary function. However, the procedure causes severe pain due to thoracic expansion. This study was designed to investigate the analgesic effect of small doses of ketamine on an intravenous patient-controlled analgesia (IV-PCA) using hydromorphone and ketorolac for pain control after Nuss surgery. METHODS: Forty-four patients undergoing elective Nuss surgery were randomly assigned to receive hydromorphone 3 microg/kg/hr, ketorolac 0.05 mg/kg/hr and ondansetron 0.1 mg/kg/day (Group HO, n = 22) or hydromorphone 3 microg/kg/hr, ketorolac 0.05 mg/kg/hr, ondansetron 0.1 mg/kg/day and ketamine 0.15 mg/kg/hr (Group HK, n = 22) via an IV-PCA pump after surgery. A blind observer evaluated each patient using the Modified Children's Hospital of Eastern Ontario Pain Scale (CHEOPS) for the assessment of pain control. The total administered PCA volume, side effects and parents satisfaction with pain control were assessed at postoperative 1, 4, 8, 12, 24, and 48 hours. RESULTS: There were no significant differences in Modified CHEOPS between the groups during postoperative 48 hours. The total PCA volume in group HK was significantly lower than that in group HO (P < 0.05). The side effects in both groups did not significantly differ except for pruritus. The levels of satisfaction from the parents were not significantly different between the groups. CONCLUSIONS: A small dose of ketamine on IV-PCA reduced the total administered dose of IV-PCA with hydromorphone and ketorolac and reduced the incidence of pruritus after the Nuss procedure in pediatric patients.
Analgesia, Patient-Controlled ; Cosmetics ; Funnel Chest ; Humans ; Hydromorphone ; Incidence ; Ketamine ; Ketorolac ; Ondansetron ; Ontario ; Parents ; Passive Cutaneous Anaphylaxis ; Pruritus

BACKGROUND/AIMS: OROS hydromorphone is a synthetic opioid agent. While clinical studies have tested its effectiveness at controlling cancer-associated pain in patients who have received other strong opioids, no clinical studies have tested its effectiveness at managing cancer pain in strong opioid-naive patients. We performed the present study to evaluate the efficacy and tolerability of OROS hydromorphone in strong opioid-naive cancer patients. METHODS: We administered OROS hydromorphone to patients who had not received strong opioids during the previous month. The starting dose was 8 mg/day. The dose was increased every 2 days in patients who experienced more than four episodes of breakthrough pain per day (more than four times in patients being treated with short-acting opioids). We evaluated the efficacy, safety and tolerability of ORS hydromorphone. We also evaluated patient satisfaction and investigators' global assessments. RESULTS: We enrolled 23 patients to the study. The decrease in the numeric rating scale (NRS) was 59%. NRS variation had decreased markedly during the previous 24 h. All patients achieved stable pain control. The side effects were similar to those of other strong opioids. In total, 26% of patients were very satisfied with the treatment and 47% satisfied, and 74% of the investigators deemed OROS hydromorphone to be very effective or effective at controlling cancer pain. CONCLUSIONS: OROS hydromorphone is an osmotically driven, controlled-release preparation that is very effective and safe when administered once daily to strong opioid-naive cancer patients.
Analgesics, Opioid ; Breakthrough Pain ; Delayed-Action Preparations ; Electrolytes ; Humans ; Hydromorphone ; Patient Satisfaction ; Prospective Studies ; Research Personnel

PURPOSE: To compare the efficacies and side effects of intravenous hydromorphone and pethidine in the emergency department (ED) treatment of ureteral colic. METHODS: A prospective, controlled, randomized clinical trial was conducted in a university-affiliated tertiary referral center. All adult patients who presented to the ED with severe ureteral colic were included. The patients received either 1 mg of hydromorphone (n=26) or 50 mg of pethidine (n=26) intravenously. Pain intensity was determined using a 10 cm visual analogue scale 0, 15, 30, and 120 minutes after injection. RESULTS: Dermographic characteristics and baseline pain scores of both groups were comparable (p>0.05). The pain intensity level for the hydromorphone group was lower than for the pethidine group at 15, 30, and 120 minutes. Pain relief was better with hydromorphone at 15 minutes (p<0.05). Side effects of the two groups were not statistically significant. CONCLUSION: The ureteral colic patients receiving hydromorphone achieved more pain relief. The side effects were similar for either treatment. Hydromorphone should be the preferred agent in suspected ureteral colic, when an opioid analgesic is to be used.
Adult ; Benzeneacetamides ; Emergencies ; Humans ; Hydromorphone ; Meperidine ; Piperidones ; Prospective Studies ; Renal Colic ; Tertiary Care Centers ; Ureter

BACKGROUND: Postoperative nausea and vomiting (PONV) is common complication of Patient-Controlled Analgesia (PCA) after surgery. The authors sought to determine whether a transdermal scopolamine (TDS) patch in combination with IV dexamethasone is more effective than IV dexamethasone alone or IV dexamethasone plus IV ramosetron for reducing PONV in patients receiving epidural PCA after major orthopedic surgery. METHODS: 120 patients that received epidural PCA with hydromorphone and ropivacaine after major orthopedic surgery under spinal anesthesia were allocated to 3 groups: Group D (n = 40) received IV dexamethasone 8 mg, Group DR (n = 40) received IV dexamethasone 8 mg plus IV ramosetron 0.3 mg, Group DS (n = 40) received IV dexamethasone 8 mg plus a TDS patch (Group DS, n = 40). Nausea and vomiting incidences, VAS for nausea, the use of additional antiemetics, and adverse effects (a dry mouth, blurred vision, drowsiness) during the first 24 hours postoperatively were subjected to analysis. RESULTS: The DS Group had a significantly higher rate of complete remission of PONV than the D and DR groups (82.5% vs 47.5%, and 50.0%, respectively), and had lower rates of nausea (17.5% vs 55.0%, and 50.0%), and vomiting (10.0% vs 50.0%, and 25.0%), and required less antiemetics (5.0% vs 35.0%, 22.5%) than group D and Group DR during the first 24 hours after surgery. Furthermore, no inter-group differences were observed with respect to adverse effects in the three groups. CONCLUSIONS: The prophylactic use of a TDS patch plus dexamethasone was found to be a more effective means of preventing PONV in patients that received epidural PCA after major orthopedic surgery than dexamethasone alone or dexamethasone plus ramosetron without adversely affecting side effects.
Amides ; Analgesia, Patient-Controlled ; Anesthesia, Spinal ; Antiemetics ; Benzimidazoles ; Dexamethasone ; Humans ; Hydromorphone ; Incidence ; Mouth ; Nausea ; Orthopedics ; Passive Cutaneous Anaphylaxis ; Postoperative Nausea and Vomiting ; Scopolamine Hydrobromide ; Sorbitol ; Tyramine ; Vision, Ocular ; Vomiting