First-line methadone for cancer pain: titration time analysis.

BACKGROUND: Methadone is a low-cost, strong opioid that is increasingly used as a first-line treatment for pain in palliative care (PC). Its long and unpredictable half-life and slow elimination phase can make titration challenging. Evidence for titration modalities is scarce. OBJECTIVE: To describe the titration phase of the treatment with low-dose first-line methadone and the use of methadone for breakthrough pain. METHODS: Prospective study with strong opioid-naïve patients with moderate to severe cancer pain followed at a tertiary PC unit in Argentina. Starting methadone dose was 2.5-5 mg/day every 8, 12, or 24 h. Titration allowed daily dose increases from day 1, and prescription of oral methadone 2.5 mg every 2 h with a maximum of 3 rescue doses/day for breakthrough pain. Pain control, methadone stabilization dose, and adverse effects, among other variables, were daily assessed over the first 7 days (T0-T7). RESULTS: Sixty-two patients were included. Initial median (IQR) methadone dose was 5 (2.5) mg/day. Pain intensity decreased from a median (IQR) of 8 (2.3) at T0 to 4 (2.3) at T1 and remained ≤ 4 until T7 (all p < 0.0001 compared to T0). Similar results were obtained through the categorical and tolerability scales for pain. Fifty patients (81%) reached pain control, 66% in the first 48 h. Methadone daily doses at T2 and T7 were higher than that at T0: 7.5 (3) and 6.7 (5.5) versus 5 (2.5), respectively (all p < 0.05). The opioid escalation index at T7 was 1.7%. The median (IQR) number of rescues, stabilization dose, and time for stabilization was 0 (1), 5(4.5) mg, and 3(2) days, respectively. Two patients were discontinued due to delirium. All other side effects were mild. CONCLUSIONS: First-line, low-dose methadone using rescue methadone resulted in a pronounced and rapid decrease in pain, with minimal need for titration and for breakthrough doses, and no evidence of accumulation or sedation by the end of the week.

Methadone as first-line opioid treatment for cancer pain in a developing country palliative care unit.

PURPOSE: The use of methadone for cancer pain is limited by the need of expertise and close titration due to variable half-life. Yet, it is a helpful palliative strategy in low-resources countries given its long-acting effect at low cost and worth additional study. Our aim was to describe the prescription and outcomes of methadone as a first-line treatment for cancer pain in a tertiary palliative care unit (PCU) in Argentina. METHODS: Retrospective review of medical records of patients with moderate to severe cancer pain seen at the PCU in 1-year period, who initiated strong opioids at the first consultation. Data collected during the first month of treatment included disease and pain characteristics, initial and final opioid type and dose and need for opioid rotation. RESULTS: Methadone was the most frequent opioid both at the initial and last assessment (71 and 66 % of the prescriptions). In all, treatment with strong opioids provided considerable decrease in pain intensity (p < 0.001) with low and stable opioid dose. Median and interquartile range (IR) of oral morphine equivalent daily dose (OMEDD) was 26 (16-32) and 39 (32-55) mg for initial and final assessments, respectively (p = 0.3). In patients initiated with methadone, the median (IR) daily methadone dose was 5 (4-6) mg at first and 7.5 (6-10) mg at final assessment, and the median (IR) index of opioid escalation was 0 (0-4) mg; (p < 0.05). Patients on methadone underwent less percentage of opioid rotation (15 versus 50 %; p < 0.001) and longer time to rotation (20.6 ± 4.4 versus 9.0 ± 2.7 days; p < 0.001) than patients on other opioids. CONCLUSIONS: Results indicate the preference of methadone as first-line strong opioid treatment in a PCU, providing good pain relief at low doses with low need for rotation. Several considerations about the costs of strong opioids in the region are given.

[Interconsultation on palliative care for patients with cancer in a general hospital. Features and opportunity]. / Interconsultas de cuidados paliativos para pacientes con cáncer en un hospital general. Características y oportunidad.

The international recommendations point to the early integration of palliative care (PC) in cancer through simultaneous care and training of primary teams. The PC Unit of the Hospital General de Agudos E. Tornú conducts interconsultations for hospitalized patients in the hospital and provides training to the treatment teams. The profile of the interconsultations carried out could provide important information about the characteristics of the PC intervention within the institution. The objective of this study was to retrospectively analyze the first-time interconsultations of cancer patients carried out over 2 years, focusing on temporality, identification of problems by the treating team and the PC interconsultation team, the promptness of response and the prognostic capacity of the latter. In the period, 168 interconsultations were carried out. Most patients had advanced disease, poor performance status, no possibility of oncological treatment and recent diagnosis. In approximately 25% of the cases, evidence of early intervention and participation of the pc team in decision making was found. The opportunity of PC intervention is discussed and areas needing improvement are indicated, such as the identification of non-physical symptoms and prognosis, to be considered in future care and educational activities.

Las recomendaciones internacionales apuntan a la integración temprana de cuidados paliativos (CP) en cáncer a través de la atención simultánea y del entrenamiento de los equipos primarios. La Unidad de CP del Hospital General de Agudos E. Tornú realiza interconsultas para pacientes internados en el hospital y brinda capacitación a los equipos tratantes. El perfil de las interconsultas realizadas podría brindar información importante sobre las características de la intervención de CP dentro de la institución. El objetivo de este estudio fue analizar retrospectivamente las interconsultas de primera vez de pacientes con cáncer realizadas a lo largo de 2 años, con foco en la temporalidad, la identificación de problemas por parte del equipo tratante y del equipo de interconsulta de CP, y la prontitud de respuesta y capacidad pronóstica de este último. La población atendida en interconsulta (168 casos) estuvo constituida principalmente por pacientes con enfermedad avanzada, deterioro del estado general, sin posibilidad de tratamiento oncológico y diagnóstico reciente. En aproximadamente 25% de los casos se encontraron indicios de intervención temprana y participación del equipo de CP en la toma de decisiones. Se discute la oportunidad de la intervención de CP y se señalan áreas con necesidad de mejora, como la identificación de síntomas no físicos y el pronóstico, a ser tenidas cuenta en las futuras actividades asistenciales y educativas.

Palliative care development in South America: a focus on Argentina.

Many Latin American and Caribbean national health systems mainly focus on disease prevention, prenatal assistance, undernourishment, etc. They still do not have the conditions for developing palliative care (PC). In general, quality of life during the dying process is poor, with fragmented assistance, uncontrolled suffering, poor communication between professionals, patients, and families, and a great burden on family caregivers. The development of PC in the region started around 1981, but it is still not available to an acceptable number of patients.

Methadone versus morphine as a first-line strong opioid for cancer pain: a randomized, double-blind study.

PURPOSE: To compare the effectiveness and side effects of methadone and morphine as first-line treatment with opioids for cancer pain. PATIENTS AND METHODS: Patients in international palliative care clinics with pain requiring initiation of strong opioids were randomly assigned to receive methadone (7.5 mg orally every 12 hours and 5 mg every 4 hours as needed) or morphine (15 mg sustained release every 12 hours and 5 mg every 4 hours as needed). The study duration was 4 weeks. RESULTS: A total of 103 patients were randomly assigned to treatment (49 in the methadone group and 54 in the morphine group). The groups had similar baseline scores for pain, sedation, nausea, confusion, and constipation. Patients receiving methadone had more opioid-related drop-outs (11 of 49; 22%) than those receiving morphine (three of 54; 6%; P =.019). The opioid escalation index at days 14 and 28 was similar between the two groups. More than three fourths of patients in each group reported a 20% or more reduction in pain intensity by day 8. The proportion of patients with a 20% or more improvement in pain at 4 weeks in the methadone group was 0.49 (95% CI, 0.34 to 0.64) and was similar in the morphine group (0.56; 95% CI, 0.41 to 0.70). The rates of patient-reported global benefit were nearly identical to the pain response rates and did not differ between the treatment groups. CONCLUSION: Methadone did not produce superior analgesic efficiency or overall tolerability at 4 weeks compared with morphine as a first-line strong opioid for the treatment of cancer pain.

Dexamethasone in addition to metoclopramide for chronic nausea in patients with advanced cancer: a randomized controlled trial.

Chronic nausea occurs in most patients with advanced cancer. This study was done to assess the antiemetic effects of dexamethasone in patients with chronic nausea refractory to metoclopramide. Secondary outcomes included appetite, fatigue, and pain. Fifty-one patients who had nausea (> or = 3/10 on a 0-10 scale) for > or = 2 weeks despite 48 hours of oral metoclopramide therapy (40-60 mg/day) were enrolled. Patients received 20 mg/day dexamethasone (DM) orally (n = 25) or placebo (n = 26) for severe nausea in addition to metoclopramide (60 mg/day orally). At baseline the mean nausea intensity ratings in the DM and placebo groups were 8.0 and 7.4. At Day 8 they were 2.1 and 2.0, respectively. At Day 3 and Day 8, the mean difference in nausea intensity for the DM and placebo groups was 4.5 and 2.9 (P = 0.16) and 5.9 and 5.7 (P = 0.85), respectively. Improvement in appetite and fatigue were observed on Day 3 and Day 8 in both groups as compared with the baseline. Pain, vomiting, well-being, and quality of life remained unchanged in both groups at both times. We conclude that DM was not superior to placebo in the management of chronic nausea in our patients with advanced cancer.

Medical students' palliative care education in a Latin American university: a three-year experience at Austral University in Buenos Aires, Argentina.

BACKGROUND: The School of Medicine of Austral University incorporated palliative care as an elective in undergraduate medicine curriculum during 2010. OBJECTIVE: We analyzed the experience and results after 3 years of teaching palliative care. We compared students who chose palliative care as an elective subject (PC Group) with students who did not (Non-PC Group). We focused on the experience of contact with palliative care patients and self-perceived attitudes. Additionally, the impact produced by palliative care education in knowledge, self-perceived attitudes, and comfort was evaluated. METHODS: All the students tested completed a questionnaire on their attitude when exposed to dying patients. Students in the PC Group completed an additional questionnaire to assess their level of knowledge and their self-perceived comfort when interacting with patients. RESULTS: We tested 146 students. All students in the PC Group and 95.2% in the Non-PC Group considered that specific death issues ought to be part of the curriculum. Some students indicated that they could be present in a mandatory course. Before taking their elective, students in the PC Group confirmed a lack of technical training to understand palliative care patients, as did those students in the Non-PC Group. After taking a palliative care elective students expressed an improvement in self-perceived attitudes toward suffering and there was a significant increase (p<0.0001-0.0045) in knowledge. They also expressed an improvement in comfort levels in evaluation and treatment of pain. More than 95% of the students in the PC Group rated the experience as valuable and perceived the content as not available elsewhere in their training. DISCUSSION/CONCLUSION: Our results show that palliative care education provides opportunities to improve attitudes not specific to this discipline: interprofessional collaboration, holistic care, patient-centered care, self-awareness, and humanism. We conclude that an exposure to palliative care improved student's perception about the complexities of dying patients and their care.

Interconsultas de cuidados paliativos para pacientes con cáncer en un hospital general: Características y oportunidad / Interconsultation on palliative care for patients with cancer in a general hospital. Features and opportunity

Las recomendaciones internacionales apuntan a la integración temprana de cuidados paliativos (CP) en cáncer a través de la atención simultánea y del entrenamiento de los equipos primarios. La Unidad de CP del Hospital General de Agudos E. Tornú realiza interconsultas para pacientes internados en el hospital y brinda capacitación a los equipos tratantes. El perfil de las interconsultas realizadas podría brindar información importante sobre las características de la intervención de CP dentro de la institución. El objetivo de este estudio fue analizar retrospectivamente las interconsultas de primera vez de pacientes con cáncer realizadas a lo largo de 2 años, con foco en la temporalidad, la identificación de problemas por parte del equipo tratante y del equipo de interconsulta de CP, y la prontitud de respuesta y capacidad pronóstica de este último. La población atendida en interconsulta (168 casos) estuvo constituida principalmente por pacientes con enfermedad avanzada, deterioro del estado general, sin posibilidad de tratamiento oncológico y diagnóstico reciente. En aproximadamente 25% de los casos se encontraron indicios de intervención temprana y participación del equipo de CP en la toma de decisiones. Se discute la oportunidad de la intervención de CP y se señalan áreas con necesidad de mejora, como la identificación de síntomas no físicos y el pronóstico, a ser tenidas cuenta en las futuras actividades asistenciales y educativas.

The international recommendations point to the early integration of palliative care (PC) in cancer through simultaneous care and training of primary teams. The PC Unit of the Hospital General de Agudos E. Tornú conducts interconsultations for hospitalized patients in the hospital and provides training to the treatment teams. The profile of the interconsultations carried out could provide important information about the characteristics of the PC intervention within the institution. The objective of this study was to retrospectively analyze the first-time interconsultations of cancer patients carried out over 2 years, focusing on temporality, identification of problems by the treating team and the PC interconsultation team, the promptness of response and the prognostic capacity of the latter. In the period, 168 interconsultations were carried out. Most patients had advanced disease, poor performance status, no possibility of oncological treatment and recent diagnosis. In approximately 25% of the cases, evidence of early intervention and participation of the pc team in decision making was found. The opportunity of PC intervention is discussed and areas needing improvement are indicated, such as the identification of non-physical symptoms and prognosis, to be considered in future care and educational activities.

Coadministración de oxicodona y metadona para reducir la neurotoxicidad opioide y proveer analgesia: presentación de un caso / Co-administration of oxycodone and metadone to reduce central nervous system side-effects and provide analgesia: case report

Este artículo describe la coadministración de dos opioides agonistas en un paciente que padece dolor de origen oncológico, con la intención de disminuir la toxicidad opioide sobre el Sistema Nervioso Central y mantener un adecuado nivel de analgesia. La oxicodona y la metadona, usualmente utilizadas en humanos, son eficaces analgésicos alternativos de la morfina para tratar dolor moderado a severo. Está bien establecido que la oxicodona actúa sobre los receptores Mu y recientemente se determinó su acción sobre los receptores Kappa. La metadona, por el contrario, es agonista Mu y antagonista competitivo del receptor N-Metil-Di-Aspartato (NMDA). Cuando se los administra conjuntamente, se amplia el espectro de acción sobre diferentes receptores; esto permite disminuir la dosis de cada uno de ellos y contribuir así a revertir la neurotoxicidad opioide que presentaba el paciente. Sin embargo, es necesario realizar trabajos de investigación clínica controlados que avalen esta presunción teórica.

Análisis ético del tratamiento de pacientes con cáncer avanzado / Ethic analysis of treatment patients with advanced cancer

La mayoría de los artículos sobre ética aplicada a los cuidados paliativos se refieren a la toma de decisiones en la atención de pacientes con cáncer avanzado. Relacionan las diferentes maniobras de esta especialidad médica con los principios de la bioética. Este artículo analiza, desde la perspectiva ética, el modelo de atención de los pacientes con cáncer avanzado y describe las transgresiones que produce en los principios de la ética médica. Y sugiere como soluciones al problema un modelo de atención continua y la creación de un programa nacional de Cuidados Paliativos.