The applications of intravenous opioids and multimodal analgesia in cancer pain man-agement / 中国肿瘤临床

The management of refractory cancer pain remains a challenge for oncologists and pain physicians worldwide.Although a large number of patients with cancer pain benefit from oral analgesics in the early stages,single oral opioids tend to be less effective in patients with the advanced disease and refractory cancer pain;for this,intravenous opioid administration is the most commonly used rapid analgesic option.Currently,the increasing clinical use of opioid-patient controlled intravenous analgesia(PCIA)has generat-ed extensive discussion on its indications,drug selection,titration,and other related topics.In addition,with the rapid development of multimodal analgesia,the individualized measures for cancer pain management show a broader exploratory scope.We will review the above topics in this article with the hope of providing some references for treatment optimization in refractory cancer pain manage-ment.

Caracterización del uso de metadona en pacientes paliativos en el Instituto Nacional del Cáncer, Santiago de Chile / Characterization of methadone use in palliative patients at the National Cancer Institute, Santiago, Chile

OBJETIVOS: realizar un estudio de tipo descriptivo y retrospectivo para caracterizar el uso y efecto de metadona en una población de pacientes de la unidad de cuidados paliativos del Instituto Nacional del Cáncer. MATERIALES Y MÉTODOS: los datos analizados se obtuvieron desde los registros de la farmacia y las fichas clínicas de los pacientes de la unidad de cuidados paliativos del Instituto Nacional del Cáncer que estaban siendo tratados con metadona durante el mes de agosto de 2013. las variables cuantificadas fueron edad, sexo, diagnóstico oncológico, tipo de dolor, motivo de indicación de metadona, duración del tratamiento, dosis utilizadas, respuesta analgésica y uso concomitante con analgésicos no opioides. RESULTADOS: la población de pacientes bajo control mensual en la unidad de cuidados paliativos al mes de agosto fue de 445 pacientes. en el estudio se incluyeron a 31 pacientes que estaban en ese periodo tratados con metadona, lo que representa un 7% del total de pacientes. la indicación, según tipo de dolor, fue en un 80,6% por dolor de tipo neuropático o mixto. la indicación de metadona se debió, en un 68%, a una rotación de opioides y solo en un 3% fue por indicación primaria. la dosis promedio diaria fluctuó entre 16,7 mg, al inicio del tratamiento; y 26,1 mg, al momento del estudio o periodo de observación. la mediana de uso fue de 211 días. la intensidad del dolor, medida por la escala numérica verbal, fue de 8,3 ± 0,3 mg al inicio del tratamiento y 5,4 ± 0,6 mg durante el control de agosto de 2013, lo que significa una disminución promedio de 34,9%. DISCUSIÓN: el uso de metadona en la unidad de cuidados paliativos del Instituto Nacional del Cáncer está en concordancia con las propuestas internacionales, indicándose principalmente como rotación de opioides y en el tratamiento del dolor neuropático. el análisis de las fichas mostró utilización de dosis bajas de metadona (menores de 30 mg), con pequeños incrementos de dosis durante el período de tratamiento, obteniéndose como resultado una reducción significativa del dolor.

OBJETIVES: to carry out a descriptive and retrospective study to characterize the use and effect of methadone in a group of patients of the Palliative Care Unit of the National Cancer Institute. MATERIALS AND METHODS: the information was obtained from the patient pharmacy and clinical records at the palliative care unit of the National Cancer Institute who were being treated with methadone during the month of august, 2013. the variables assessed were age, sex, oncology diagnosis, type of pain, reason for methadone prescription, treatment duration, dosage, pain response and associated use of non- opioid analgesics. RESULTS: the patient group under monthly monitoring at the palliative care unit in august was made up of 445 people. the study included 31 patients who at that time were being treated with methadone, 7% of the total. the indication according to the type of pain was in an 80.6% caused by a neuropathic or mixed pain. a 68% of the methadone indication was caused by an opioid rotation and only a 3% by a primary indication. the average daily dose went from 16.7 mg at the beginning to 26.1 mg at the moment the study or observation period was carried out. the use average was of 211 days. The pain intensity, using a numeric scale, was of 8.3 ± 0.3 mg at the beginning of the treatment and a 5.4 ± 0.6 mg during the august 2013 control, which means an average decrease of 34,9 %. DISCUSSION: the use of methadone at the palliative care unit of the National Cancer Institute is in accordance with the international proposals, being indicated mostly as opioid rotation and in the neuropathic pain treatment. the record analysis showed a low dose use of methadone (lower than 30 mg), with small dose increase during the treatment period, getting a significant pain decrease as a result

Guidelines for prescribing opioids for chronic non-cancer pain in Korea

As the treatment of chronic non-cancer pain gradually increases, clinicians have more opportunities to encounter opioid prescription. However, guidelines for prescribing opioids for chronic non-cancer pain have never been published in Korea. The present guidelines were prepared by reviewing various research data. In cases in which the data were insufficient, recommendations were presented following discussion among experts affiliated with the Opioids Research Group in the Korean Pain Society. The present guidelines may need to be continuously revised and amended as more clinical evidence is acquired.

Dose conversion ratio for continuous intravenous infusion of fentanyl and fentanyl transdermal patches (reservoir-type)

Objectives: At present, the dose conversion ratio for a continuous intravenous infusion of fentanyl (CIV) and fentanyl transdermal patches (TP), which are widely used in Japan, is not based on the results of clinical studies in Japanese patients. Studies comparing serum fentanyl concentrations in patients with cancer pain treated by TP showed large differences between Japanese patients and those in other countries. We therefore studied the dose conversion ratio in Japanese patients. Methods: From October 2003 through October 2008, we extracted information on all patients with gastrointestinal cancer who underwent rotation from CIV to TP in the gastrointestinal ward of Kitasato University East Hospital. We selected patients in whom the daily dose of CIV or TP (i.e., the basic dose) was unchanged for 10 days after rotation and the difference in the number of rescue doses (per day) as compared with immediately before rotation was 1 or less on at least 3 consecutive days. All TP preparations used in this study were reservoir-type. Regression lines were plotted on the basis of the relation of “the basic released dose of TP” to “the basic prescribed dose of CIV,” and the dose conversion ratio was calculated. Results: 47 patients underwent opioid rotation, and 11 of them satisfied the eligibility criteria. Eleven patients were studied. The following regression equation was obtained: Y=1.0227X+1.0103, r²=0.9188, indicating a strong correlation. The dose conversion ratio of CIV to TP (released dose) derived by regression analysis was 1:1. Conclusions: Our results obtained in Japanese patients will allow dose conversion at the time of opioid rotation from CIV to TP to be more appropriately performed.

The opioid rotation from high-dose transdermal fentanyl to sustained release oxycodone for refractory cancer pain

<b>Purpose</b>: Traditionally, opioids have been the cornerstone of therapy for patients suffering from cancer pain, regardless of the potential to develop opioid tolerance. In chronic pain patients who experience improving pain by opioid rotation, the clinical role of opioid tolerance is gaining more recognition. <b>Case Report</b>: Presented here is the case of a 60-year-old man with recurrent rectal carcinoma with huge pelvic mass and iliac and neck of femur bone metastases, suffering with intractable 9/10 pain on the numerical rating scale in his right hip and leg. In spite of escalating doses of fentanyl to 50.4 μg/72 hours and started gabapentin for adjunctive pain treatments, the patient continued to experience severe pain. The clinical picture suggested the possibility of opioid torelance. We decreased the fentanyl dose and started oxycodone. Opioid rotation to 30 mg/day sustained release oxycodone and withdrawed fentanyl provided effective pain control. The patient's pain level dropped to a more acceptable 2/10. He was more alert, and his pain was tolerable until his death. <b>Conclusion</b>: Opioid tolerance might be considered in a patient who has no evidence of disease progression, who is on clinically reasonable doses of opioids. Opioid rotation may provide a favorable clinical outcome in those patients who have failed to benefit from adjunctive pain treatments. Palliat Care Res 2011; 6(1): 330-335

The effective rotation dose from fentanyl transdermal patch to other opioids

<b>Purpose</b>: A case of effective pain control by opioid rotation from fentanyl patch (oral morphine:fentanyl=100: 1 ratio) was succeeded with less than the theoretically equivalent conversion dose. Therefore, an investigation was undertaken to determine the effective rotation dose from fentanyl patch to other opioids. <b>Methods</b>: Retrospective analysis was carried out on patients with cancer-related pain, who were switched from fentanyl patch to other opioids. <b>Results</b>: Fourteen patients were analyzed and the average effective dose of opioids after the rotation was 76% of the theoretically calculated dose. Effective doses after opioid rotation were less than calculated doses in 11 cases (79%) and more than calculated doses in only 3 cases (21%). Effective doses after opioid rotation were 101% of calculated doses in cases (n=5) with less than 75μg/hr of fentanyl patch, but 63% in cases (n=9) with more than 75μg/hr. <b>Conclusion</b>: Opioid rotation should be considered when administration of more than 75μg/hr of fentanyl patch is needed. It is necessary to reduce the amount of applied dose to approximately 60% of calculated dose for safe opioid rotation. Moreover, it is necessary to remain careful and to provide immediate assistance in case of emergency due to withdrawal syndrome. Palliat Care Res 2009; 5(1): 301-307

Rotación a metadona para el dolor por cáncer: estudio prospectivo / Switching to metadone for cancer pain: prospective study

El objetivo de este estudio fue evaluar los beneficios de la rotación de morfina a metadona oral en pacientes con poca respuesta analgésica o efectos adversos derivados de la morfina. Diecisiete pacientes con cáncer avanzado que recibían morfina por dolor no controlado o efectos adversos severos fueron rotados a metadona cada ocho o doce horas, según un esquema de rotación rápida utilizando diferentes dosis ratios. La intensidad del dolor y efectos adversos fueron evaluados diariamente y comparados antes y después del cambio. Se documentó la dosis de morfina prerrotación, la dosis media inicial de metadona, dosis al séptimo día así como la dosis media final. Antes de la rotación la dosis media equivalente de morfina oral fue 118.71 mg/día, luego de la misma la dosis media inicial de metadona fue de 17.94 mg/día, al séptimo día fue 27.06 mg/día y la dosis media final de metadona fue 34.12 mg/día. Los motivos de la rotación fueron: dolor no controlado, efectos adversos limitantes o la suma de ambos. Se encontraron mejorías significativas en la analgesia (p<0.05) así como alivio sintomático relevante en los efectos adversos. Se registraron efectos colaterales debidos a la utilización de metadona en ocho pacientes que revirtieron con el tratamiento sintomático. La metadona demostró ser una opción terapéutica válida para el grupo de pacientes estudiados. Se recomienda precaución en la rotación a metadona en pacientes tolerantes a altas dosis de opioides.

The aim of this study was to evidence the clinical benefits of switching from morphine to oral methadone in patients who experience poor analgesia or adverse effects from morphine. Seventeen advanced cancer patients receiving morphine but with uncontrolled pain or severe opioid adverse effects were switched to oral methadone administered every 8 or 12 hours according to a scheme of rapid switching using different dose ratios.Intensity of pain and adverse effects were assessed daily and compared before and after switching. Pre switching doses of morphine, initial, day 7 and final methadone doses were recorded. Before the switch, the median equivalent daily dose of morphine was 118.71 mg/day; after the switch the initial dose of methadone (median) was 17.94 mg/day, 27.06 mg/day at day 7 and the final dose of methadone (median) was 34.12 mg/day. The reasons for switching were: uncontrolled pain, adverse effects or both. Significant improvements in pain (p<0.05) and relevant changes in adverse effects were reported. Methadone - related side effects reported in 8 patients were relieved after treatment. In patients with cancer pain and/or adverse effects of oral methadone is a valid therapeutic option.Caution is recommended when switching from any opioid to methadone, in patients who are tolerant to high doses of opioids.

O objetivo deste estudo foi avaliar os benefícios da passagem de morfina a metadona oral em pacientes com pouca resposta analgésica o efeitos adversos derivados da morfina. Dezessete pacientes com câncer avançado que recebiam morfina por dor não controlada o efeitos adversos severos foram medicados com metadona cada 8 ou 12 horas, adotando um esquema de conversão rápida utilizando diferentes doses-ratios. A intensidade da dor e efeitos adversos foi avaliada diariamente e comparados antes e depois da troca. Foi documentado a doses de morfina pré-conversão, a doses media inicial de metadona, a dosagem ao dia 7, como também a doses media final. Antes da troca a doses media equivalente de morfina oral foi de 118.71 mg/dia, logo após as doses media inicial de metadona foi de 17.94 mg/dia, ao dia 7 foi de 27.06 mg/dia e a doses final de metadona foi 34.12 mg/dia. O motivo da passagem a metadona foi: dor não controlada, efeitos adversos limitantes o a soma deles. Foram encontradas melhorias significativas na analgesia (p<0.05) alem do alivio relevante dos efeitos adversos. Se registraram efeitos colaterais pela utilização da metadona em 8 pacientes que melhoraram com o tratamento sintomático. A metadona demonstrou ser uma opção terapêutica valida para o grupo de pacientes estudados. Recomendamos cuidados na passagem a metadona em pacientes tolerantes a altas doses de opioides.

A case of gastric cancer with abdominal pain in whom successful pain control was achieved by opioid rotation to morphine

<b>Introduction</b>: Although fentanyl patch (FP) are often used to treat cancer pain because of the low incidence of adverse effects of this formulation, there are cases in which it is impossible to eliminate the pain despite increasing the doses. We report a patient of advanced gastric cancer with abdominal pain, in whom successful pain control was achieved by opioid rotation from FP to continuous intravenous infusion of morphine hydrochloride. <b>Case Report</b>: The patient was a male in his 60's who had been diagnosed as having primary gastric cancer and complained of abdominal pain, thought to be visceral pain caused by obstruction of the digestive tract. Oral intake became more difficult as the disease progressed. Despite a switch to FP from oxycodone used to treat the abdominal pain and an increase in the dose, pain relief was not achieved. Then, we undertook a partial opioid rotation to continuous intravenous infusion of morphine hydrochloride, which provided adequate pain control. <b>Discussion</b>: One possible reason for the pain relief in this patient is suppression of the gastrointestinal motility by morphine. When adequate pain relief cannot be achieved with one opioid, opioid rotation should be considered. We concluded that the opioid rotation should, however, be performed in a stepwise manner. Palliat Care Res 2009; 4(1): 307-311

Opioid rotation to oral morphine in the treatment of cancer pain not responding to transdermal fentanyl escalation

<b>Purpose</b>; Transdermal fentanyl (TF) has less systemic adverse effects as compared to morphine. However, few patients with cancer related pain obtain insufficient analgesic response despite the dose escalation of TF. The aims of this study were to describe patients with poor analgesic response and to evaluate the efficacy of opioid rotation from TF to oral morphine. <b>Case reports</b>; We conducted a retrospective chart review and analyzed six patients managed with opioid rotation in detail. Before opioid rotation, an average dose of TF was 204μg/hr. A significant decrease in pain score was found in all patients who switched to oral morphine, and five patients were treated with the combination of TF and oral morphine. <b>Conclusion</b>; These results may indicate that patients who are treated with relative high dose TF (over 200μg/hr) tended to response to poor analgesic, and opioid rotation is beneficial to restore the analgesic effects. We speculate that this clinical phenomenon is associated with opioid tolerance.