Problemas con la rotación de opiáceos: sustitución dela metadona por otro opiáceo en pacientes con dolorrelacionado con cáncer / Pitfalls of opioid rotation: substituting another opioid for methadone in patients with cancer pain

La eficacia de la metadona en el dolor relacionado con cáncer ha sido demostrada por numerosos informes de casos y estudios clínicos. La metadona suele utilizarse como medicación opiácea de segunda o tercera fila. Con el creciente uso de la metadona, nos enfrentamos al reto de sustituirla por otros opiáceos como parte de los tratamientos secuenciales con opiáceos. En este artículo presentamos los datos prospectivos de 13 rotaciones consecutivas de metadona a otro opiáceo. La rotación de opiáceos fue seguida por un aumento del dolor y/o disforia severa, sin que pudieran controlarse con un rápido aumento de la dosis del segundo opiáceo, en 12 de los 13 pacientes. Sólo un paciente se mantuvo bien con el segundo opiáceo después de suspender la metadona, mientras que 12 pacientes tuvieron que volver a recibir metadona. Concluimos que la rotación de la metadona a otro opiáceo suele complicarse por un agravamiento del dolor y la presencia de disforia. Estos síntomas no siempre mejoran a pesar de aumentar la dosis del segundo opiáceo. Actualmente no existe un índice de conversión unánimamente aceptado para sustituir la metadona por otro opiáceo. Se necesitan más datos sobre la rotación de metadona a otros opiáceos (AU)

A safe and effective method for converting cancer patients from intravenous to transdermal fentanyl.

BACKGROUND: Therapeutic fentanyl blood levels are reached approximately 12-16 hours after the initial application of transdermal fentanyl patches. For this reason, fentanyl patches should not be used to treat acute exacerbations of cancer pain. Acute cancer-related pain can be treated with fentanyl administered by continuous intravenous infusion (CII) in combination with patient-controlled analgesia (PCA). Patients then can be switched from intravenous (IV) to transdermal fentanyl once stable pain relief has been achieved. The objective of the current case series was to evaluate and describe the safety and effectiveness of a method for converting hospitalized patients with cancer-related pain from IV to transdermal fentanyl. METHODS: The authors prospectively evaluated 15 consecutive cancer patients during the conversion from IV to transdermal fentanyl. In all patients, a transdermal patch delivering fentanyl at a rate equivalent to that of the final continuous IV infusion was applied. The CII rate was decreased by 50% 6 hours after application of the fentanyl patch and then discontinued after another 6 hours. Demand boluses of IV fentanyl equivalent in dosage to 50-100% of the final CII rate remained available via PCA during the 24 hours after patch application. Pain intensity (on a scale of 0-10), sedation (on a scale of 0-3), and hourly PCA administration (microg/hr) were assessed and recorded immediately prior to application of the fentanyl patch and 6, 12, 18, and 24 hours thereafter. RESULTS: Pain intensity, sedation, and hourly PCA administration appeared to remain stable throughout the transition from IV to transdermal fentanyl. CONCLUSIONS: The results of the current study demonstrate that the conversion from IV to transdermal fentanyl can be accomplished safely and effectively using a 1:1 (IV:transdermal) conversion ratio and a two-step taper of the CII over 12 hours.

Intravenous methadone in the management of chronic cancer pain: safe and effective starting doses when substituting methadone for fentanyl.

BACKGROUND: Patients often are rotated from other opioids to methadone when side effects occur before satisfactory analgesia is achieved. Various strategies have been proposed to estimate safe and effective starting doses of methadone when rotating from morphine and hydromorphone; however, there are no guidelines for estimating safe and effective starting doses of methadone when rotating from fentanyl. METHODS: The authors prospectively observed 18 consecutive patients experiencing chronic pain from cancer who underwent opioid rotation from intravenous patient-controlled analgesia (PCA) with fentanyl to intravenous PCA with methadone. Patients were switched from fentanyl to methadone because of uncontrolled pain associated with sedation or confusion. A conversion ratio of 25 microg/hour of fentanyl to 0.1 mg/hour of methadone was used to calculate the initial dose of methadone in all patients. RESULTS: Mean pain scores decreased from 8.1 to 4.8 on Day 1 after the switch and to 3.22 on Day 4 after the switch. Mean sedation scores were 1.5 before the switch and 0.44 and 0.16 on Days 1 and 4, respectively. Among the 6 patients who experienced confusion while on fentanyl before the switch, 5 improved within 2 days of the switch. None of the patients experienced toxicity from methadone. CONCLUSIONS: On the basis of this preliminary study, the authors suggest that when switching from intravenous fentanyl to methadone a conversion ratio of 25 microg/hour of fentanyl to 0.1 mg/hour of methadone may be safe and effective.

Diphenhydramine as an analgesic adjuvant in refractory cancer pain.

Clinical and animal data suggest that antihistamines may have efficacy in the management of pain. While many mechanisms of action have been proposed for the analgesic action of antihistamines, the exact mechanism is unknown. Controlled clinical trials in different pain models have demonstrated that antihistamines have direct and adjuvant analgesic activity. We report three patients with advanced cancer pain refractory to adjuvants and oral, intravenous, and epidural opioids, who achieved sustained pain relief after the repeated administration of diphenhydramine. Diphenhydramine may be useful in the treatment of neuropathic and nociceptive pain that has failed to respond to treatment with opioids and adjuvant analgesics. We suggest a starting dose of 25 mg of oral or parenteral diphenhydramine every 6 to 8 hours, with titration to effect.

Methadone analgesia in cancer pain patients on chronic methadone maintenance therapy.

Methadone is currently best known for its use as the maintenance drug in opioid addiction. The main concern when using methadone for the treatment of pain is its long and unpredictable half-life, which is associated with the risk of delayed toxicity. This may result in side effects such as sedation and respiratory depression if careful titration and close observation of individual patient responses are not performed. For this reason, methadone is often viewed as a second line opioid, after other opioids with a more predictable dose-response have been tried. We report six patients with long-term exposure to methadone as a treatment for heroin dependency, who were also treated with methadone for cancer pain. The first five patients were at least partially refractory to the analgesic effects of opioids other than methadone. All six patients achieved analgesia without sedation or respiratory depression from aggressive upward methadone titration. Methadone analgesia can be considered early in the course of treatment of patients with chronic exposure to methadone who develop new or worsening pain requiring opioid therapy.