Once-Daily OROS Hydromorphone for Management of Cancer Pain: an Open-Label, Multi-Center, Non-Interventional Study

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).

The effects of hydromorphone on astrocytic responses in cerebral ischemia

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.

Orthodontic approach to treat complex hypodontia using miniscrews in a growing patient

This article reports orthodontic treatment of a case of hypodontia of five premolars in an 11-year-old female patient with a positive tooth size-arch length discrepancy in both dental arches. The patient had a straight profile with balanced facial growth. Setup manufacture revealed the possibility of achieving ideal occlusion by mesializing permanent molars up to 15 mm, in addition to keeping a primary molar in the dental arch. With the aid of absolute anchorage, the proposed mechanics was performed and the occlusion predicted in the setup was achieved, while profile and facial growth pattern were maintained. The use of miniscrews for extensive orthodontic movements was successful. Furthermore, one primary molar was extensively mesialized. The indication of gingivoplasty to correct gingival smile proved effective. This is considered a useful technique for orthodontists.

Este artigo apresenta o tratamento ortodôntico de um caso com hipodontia de cinco pré-molares, em uma paciente, de 11 anos de idade, com discrepância positiva de modelo em ambas as arcadas. A paciente apresentava perfil reto, com crescimento facial equilibrado. Por meio da confecção de set-up, verificou-se a possibilidade de se estabelecer uma oclusão ideal por meio da mesialização, de até 15mm, dos molares permanentes e manutenção de um molar decíduo no arco. Com o auxílio de ancoragem absoluta, foi realizada a mecânica proposta, alcançando-se a oclusão prevista em set-up, além da manutenção do perfil e do padrão de crescimento facial. A utilização de mini-implantes para grandes movimentos ortodônticos foi favorável, incluindo a extensa mesialização de um molar decíduo. A indicação da gengivoplastia para correção do sorriso gengival se mostrou acertada, sendo essa uma técnica de grande auxílio à Ortodontia.

Clinical benefits of preemptive thoracic epidural analgesia with hydromorphone and bupivacaine in open thoracotomy lung surgery

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.

Breakthrough Cancer Pain / 한국호스피스완화의료학회지

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.

Current Evidence for Spinal Opioid Selection in Postoperative Pain

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.

Hydromorphone attenuates intercellular adhesion molecule-1 expressions induced by lipopolysaccharide on HCT-116 human colon cancer cells / 대한마취과학회지

No abstract available.

Effect of ketamine on intravenous patient-controlled analgesia using hydromorphone and ketorolac after the Nuss surgery in pediatric patients / 대한마취과학회지

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.

Efficacy and Tolerability of OROS Hydromorphone in Strong Opioid-Naive Patients: An Open Label, Prospective Study / 대한내과학회지

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.

Emergency Department-Based Treatment of Acute Ureteral Colic with Hydromorphone and Pethidine: Prospective, Randomized Control Trial

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.

Hidromorfona de liberação lenta: uma nova opção agonista opioide forte / Slow-release hydromorphone: a new strong opioid agonist option

JUSTIFICATIVA E OBJETIVOS: A dor crônica é uma condição frequente na população mundial, sendo causa de perdas emocionais e econômicas importantes. A busca por fármacos analgésicos potentes, de longa duração de ação, que possam proporcionar estabilidade no controle em longo prazo, melhora da adesão ao tratamento com o mínimo de eventos adversos, tem crescido na última década. O mais novo membro desta classe de analgésicos é a hidromorfona OROS®, opioide forte agonista µ, que incorpora a tecnologia OROS® push-pullTM (ALZA Corporation, Mountain View, CA, USA), liberado hidromorfona, administrada por via oral, de forma constante, por 24h. O objetivo deste estudo foi descrever os aspectos farmacocinéticos e farmacodinâmicos, indicações e contra-indicações, bem como sumarizar os resultados dos principais artigos publicados, de relevância clínica, sobre a hidromorfona OROS®.CONTEÚDO: O cloridrato de hidromorfona é um analgésico opioide forte para a administração em dose única diária. A liberação controlada promove uma analgesia dose-dependente contínua, durante 24h de intervalo entre duas doses. Está indicada no tratamento da dor de moderada à intensa, crônica, maligna ou benigna. A dose inicial deve ser de 8 mg a cada 24h para pacientes que não estejam recebendo nenhum outro analgésico opioide. Para pacientes que estejam recebendo opioidespor via oral, a razão sugerida de conversão é de 5:1 de equivalentes de morfina por hidromorfona. Os estudos clínicos demonstraram um efeito analgésico contínuo ao longo de 24h em pacientes com dor moderada à intensa, maligna e não maligna. A formulação de liberação lenta proporciona analgesia estável, segura, sem a condição que comumente chamamos de "picos e vales", que favorece o aparecimento de efeitos adversos e um controle analgésico não ideal. A adesão ao tratamento e a comodidade posológica são inquestionáveis, com apenas uma administração diária. CONCLUSÃO: A hidromorfona OROS® parece ser uma opção analgésica segura e eficaz para o controle da dor crônica, de intensidade moderada à forte, não incidentais, malignas ou benignas, ajustando-se às exigências da Escada Analgésica da Organização Mundial da Saúde (3º degrau) e da analgesia multimodal.

BACKGROUND AND OJBECTIVES: Chronic pain is a common condition worldwide, being responsible for major emotional and economic losses. The search for potent long lasting analgesic drugs to provide stability for long term pain control and to improve adherence to treatment with minimum adverse events has grown during the last decade. The latest member of this class of analgesics is hydromorphone OROS®, strong µ agonist opioid, which incorporates the OROS® push-pullTM (ALZA Corporation, Mountain View, CA, USA) technology, which releases oral hydromorphone in a constant way during 24 hours. This review aimed at describing pharmacokinetic and pharmacodynamic aspects, indications and counterindications, as well as at summarizing results of major published articles of clinical relevance on hydromorphone OROS®.CONTENTS: Hydromorphone hydrochloride is a strong opioid analgesic for single daily dose administration. Controlled release promotes a continuousdose-dependent analgesia during the 24-hour interval between two doses. It is indicated to treat moderate to severe, chronic, malignant or benign pain. Initial dose should be 8 mg every 24 hours for patients not receiving any other opioid analgesic. For patients receiving oral opioids, suggested conversion ratio is 5:1 of morphine equivalents by hydromorphone. Clinical studies have shown a continuous analgesic effect for 24 hours in patients with moderate to severe, malignant or not malignant pain. The slow release formulation provides stable and safe analgesia without the condition we commonly call "peaks and valleys", which favors the onset of adverse effects and a less than ideal analgesic control. Adherence to treatment and dose convenience are unquestionable, with just one daily administration.CONCLUSION: Hydromorphone OROS® seems to be a safe and effective analgesic option to control chronic moderate to severe, non incidental, malignant or benign pain, in compliance with the requirements of World Health Organization?s Analgesic Stair (3rd step) and of multimodal analgesia.

The effect of transdermal scopolamine plus intravenous dexamethasone for the prevention of postoperative nausea and vomiting in patients with epidural PCA after major orthopedic surgery / 대한마취과학회지

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.

Comparison of hydromorphone and fentanyl administered by lumbar epidural as patient-controlled analgesia after total knee arthroplasty

BACKGROUND:Hydromorphone is a semi-synthetic opioid that has recently been used for the control of acute and chronic pain.It has been reported that epidural infusion of hydromorphone provides rapid onset of analgesia and a lower incidence of side effects than morphine.However, comparative studies of hydromorphone and lipophilic opioids such as fentanyl are rare.Therefore, we compared the analgesic effects and side effects of hydromorphone infused epidurally with fentanyl in patients who underwent total knee arthroplasty. METHODS:In a randomized, double-blind manner, 79 patients (ASA I-III, aged 60?75) underwent total knee arthroplasty and were provided with patient-controlled epidural analgesia (PCEA) using a lumbar spinal/epidural-combined technique. Group HR (n = 39) received epidurally administered hydromorphone (4microg/ml) with 0.1% ropivacaine, while group FR (n = 40) received epidural fentanyl (2microg/ml) with 0.1% ropivacaine for 24 h after surgery at a rate of 5 ml/h. The visual analogue scale (VAS) was used to evaluate pain and the incidence of side effects such as nausea/vomiting, pruritis, dizziness, and respiratory depression were recorded at 4, 8, 12, 24 h after surgery. RESULTS:Group HR showed a lower VAS than group FR at 4, 12 and 24 h after surgery, but a higher incidence of nausea and vomiting at 8 h after surgery, and a higher incidence of pruritis at 8 and 12 h after surgery. None of the patients showed respiratory depression. CONCLUSIONS:Lumbar epidural infusion of hydromorphone more effectively controlled acute pain after total knee arthroplasty when compared with fentanyl, but some adverse effects such as nausea and vomiting appeared to occur more frequently.

Comparison of hydromorphone and fentanyl administered by lumbar epidural as patient-controlled analgesia after total knee arthroplasty

BACKGROUND:Hydromorphone is a semi-synthetic opioid that has recently been used for the control of acute and chronic pain.It has been reported that epidural infusion of hydromorphone provides rapid onset of analgesia and a lower incidence of side effects than morphine.However, comparative studies of hydromorphone and lipophilic opioids such as fentanyl are rare.Therefore, we compared the analgesic effects and side effects of hydromorphone infused epidurally with fentanyl in patients who underwent total knee arthroplasty. METHODS:In a randomized, double-blind manner, 79 patients (ASA I-III, aged 60?75) underwent total knee arthroplasty and were provided with patient-controlled epidural analgesia (PCEA) using a lumbar spinal/epidural-combined technique. Group HR (n = 39) received epidurally administered hydromorphone (4microg/ml) with 0.1% ropivacaine, while group FR (n = 40) received epidural fentanyl (2microg/ml) with 0.1% ropivacaine for 24 h after surgery at a rate of 5 ml/h. The visual analogue scale (VAS) was used to evaluate pain and the incidence of side effects such as nausea/vomiting, pruritis, dizziness, and respiratory depression were recorded at 4, 8, 12, 24 h after surgery. RESULTS:Group HR showed a lower VAS than group FR at 4, 12 and 24 h after surgery, but a higher incidence of nausea and vomiting at 8 h after surgery, and a higher incidence of pruritis at 8 and 12 h after surgery. None of the patients showed respiratory depression. CONCLUSIONS:Lumbar epidural infusion of hydromorphone more effectively controlled acute pain after total knee arthroplasty when compared with fentanyl, but some adverse effects such as nausea and vomiting appeared to occur more frequently.

Tratamiento farmacológico del dolor en pacientes con cáncer: [revisión] / Pharmacological treatment of patients with cancer pain: [review]

La Organización Mundial de la Salud define el cuidado paliativo como el cuidado total y activo en aquellos pacientes que no responden a un tratamiento curativo. El control del dolor, otros síntomas y los problemas psicológicos, sociales y espirituales son de fundamental importancia. La meta del cuidado paliativo es brindar la mejor calidad de vida a los pacientes y a sus familias. En el cuidado paliativo es necesario el manejo multidisciplinario. Nuevas estrategias como rotación de opioides y sus diferentes vías de administración pueden ofrecer analgesia con pocos efectos adversos.

The World Health Organisation defines palliative care as the active total care of patients whose disease is not responsive to curative treatment. Control of pain, of other symptoms, and of psychological, social and spiritual problems, is paramount. The goal of palliative care is achievement of the best quality of life for patients and their families. Palliative care is necessarily multidisciplinary. New strategies such as the switching opioids and/or their route of administration may offer improved analgesia with fewer adverse effects, thus providing therapeutic alternatives for the clinical community.

Determination of opiates in biological human samples by liquid chromatography-tandem mass spectrometry / 法医学杂志

OBJECTIVE@#Liquid chromatography-tandem mass spectrometry (LC-MS/MS) was developed for the determination of opiates in biological samples according to the emerging problem in drugs abuse.@*METHODS@#Opiates such as heroin, 6-acetylmorphine, morphine, codeine, acetylcodeine, hydrocodone and hydromorphone were isolated from human blood, urine, oral fluid and hair using a simple extraction and consequently analyzed using LC-MS/MS. The method was evaluated by real cases.@*RESULTS@#The mobile phase give the optimum separation for opiates. The detection limit of morphine in urine with dilution and liquid-liquid extraction and in hair is 10ng/mL, 0.01 ng/mL and 0.01 ng/mg, respectively.@*CONCLUSION@#The method is simple and rapid, offering superior sensitivity and selectivity for opiates. The target compounds comprising hydrocodone and hydromorphone enlarge the applied area.

Effects of Epidural Naloxone on Pruritus Induced by Hydromorphone Epidural Patient-Controlled Analgesia / 대한통증학회지

BACKGROUND: Opioid delivered by epidural patient-controlled analgesia (PCA) is effective in relieving pain after surgery, but it is associated with side effects, such as nausea, vomiting, pruritus, respiratory depression, and urinary retention. The purpose of this study was to compare hydromorphone related side effects and the quality of analgesia when naloxone was added to epidural PCA regimen. METHODS: Fifty-two thoracotomy patients with PCA were allocated blindly into two groups. Patients in group H (n = 26) received continuous epidural hydromorphone (16microgram/ml) in 0.1% bupivacaine; patients in group N (n = 26) received an epidural infusion containing naloxone (2 microgram/ml) and hydromorphone (16microgram/ml) in 0.1% bupivacaine. The basal rate of PCA was 4 ml/hr and the demand dose was 1.5 ml with a lockout time of 15 min. Pain intensity, sedation, pruritus, nausea and vomiting, respiratory depression were checked at 6, 12, 24 hours postoperatively. RESULTS: The Visual Analog Scale (VAS) scores were significantly lower in group H than in group N. There were no significant differences in the overall incidence of pruritus, nausea and sedation between the two groups. CONCLUSIONS: Continuous epidural infusion of naloxone combined with hydromorpho-ne is not effective in reducing the incidence and severity of pruritus induced by epidural hydromorphone.

A Comparison of Hydromorphone-Bupivacaine and Fentanyl-Bupivacaine in Patient Controlled Epidural Analgesia after Thoracotomy / 대한통증학회지

BACKGROUND: Hydromorphone has an intermediate lipid solubility range that falls between morphine and fentanyl. Lipophilic activity during opioid epidural administration is important in relation to both the side effects and analgesic efficacy. The purpose of this study was to compare epidural hydromorphone and fentanyl when concomitantly infused with bupivacaine in patients undergoing a thoracotomy. METHODS: Seventy-seven thoracotomy patients, with patient-controlled epidural analgesia (PCEA), were blindly allocated into two groups [group F (n = 34); 0.1% bupivacaine and fentanyl 5microgram/ml, group H (n = 34); 0.1% bupivacaine and hydromorphone 16microgram/ml)]. The basal PCEA rate and demand dose were 4 ml/hr and 3 ml, respectively. The visual analogue scale (VAS) for pain, and pruritus, sedation and nausea were measured at 6, 12 and 24 hours after the operation. RESULTS: There were no significant differences in the VAS pain scores and the incidences of pruritus, nausea and sedation between the two groups. The total infused volume after 24 hours was lower in H compared to that of F group (P < 0.05). CONCLUSIONS: We conclude that epidural hydromorphone or fentanyl administration has a similar analgesic efficacy and shows similar incidences of side effects, when concomitantly infused with bupivacaine, in the management of acute pain following a thoracotomy.

The Efficacy and Incidence of Side Effects in Patient Controlled Analgesia Using Hydromorphone / 대한마취과학회지

BACKGROUND: Hydromorphone, a derivative of morphine, has the same actions and uses as morphine, has about eight times more potency on a milligram basis. Hydromorphone is used for the relief of moderate to severe pain. There has been no report in Korea on patient controlled analgesia (PCA) using hydromorphone. Here, the efficacy and incidence of side effects of PCA, with hydromorphone, were investigated. METHODS: 68 patients scheduled for spinal, urological, gynecological and general surgery were enrolled. Patients received standardized general anesthesia, with the PCA initiated at the end of surgery. Parameters for PCA were a 0.1 mg bolus and 0.05 mg/hr infusion of hydromorphone, with a 10 min lockout interval. A verbal rating scale (1: none, 2: very mild, 3: mild, 4: moderate, 5: severe) of pain, nausea (mild, moderate, severe), vomiting, dizziness and somnolence were assessed at 6, 12, 24 hr postoperatively. The amount of hydromorphone used and the requirements for symptomatic relief were also recorded. RESULTS: The mean pain scores were 3.5+/-0.8, 2.9+/-0.8 and 2.5+/-0.7, and the amounts of hydromorphone delivered were 1.0+/-0.1, 1.8+/-1.0 and 2.7+/-1.3 mg, 6, 12 and 24 hr postoperatively, respectively. The incidence of nausea, vomiting, dizziness and somnolence were 17.6, 4.4, 8.8 and 1.5%, respectively. CONCLUSIONS: Intravenous PCA, with hydromorphone, was effective in controlling postoperative pain, with fewer eide effects than morphine, as reported in the literature.

Determination of hydromorphone in Beagle dogs plasma by liquid chromatography-tandem mass spectrometry / 药学学报

<p><b>AIM</b>To establish a LC/MS/MS method for determination of hydromorphone (HYD) in Beagle dog plasma.</p><p><b>METHODS</b>After incubation with beta-glucuronidase for 16 h, an aliquot of 0.1 mL plasma was treated by liquid-liquid extraction. The analytes of interest were separated on a Zorbax SB C8 column with the mobile phase consisting of methanol-water- formic acid (65: 35: 1). Atmospheric pressure chemical ionization source of MS was applied and operated in positive ion mode.</p><p><b>RESULTS</b>The linear calibration curve was obtained in the concentration range of 0.80 - 200.0 microg x L(-1). The lower limit of quantification was 0.80 microg x L(-1). The inter-day and intra-day precision (RSD) was below 6.0%, and the accuracy (RE) was within 1% calculated from QC samples. The method was used to determine the pharmacokinetic parameters of HYD after a single oral administration of 4 mg HYD sustained release tablets to Beagle dogs.</p><p><b>CONCLUSION</b>The method was proved to be specific, sensitive, and suitable for the pharmacokinetic study of HYD sustained release formulation.</p>