Paolo L. Manfredi

Background: Some patients with advanced dementia cannot convey the experience of pain verbally and may react to pain with aggressive and agitated behaviors. We hypothesized that unrecognized pain could contribute to agitation and that low dose opioid therapy might reduce agitation by reducing pain. We therefore attempted to determine the effect of opioids on agitation in demented patients.Methods: We administered placebo for 4 weeks and a long‐acting opioid for another 4 weeks to nursing home patients with advanced dementia and severe agitation despite treatment with psychotropic drugs. Patients and study nurses did not know if the medication administered was placebo or opioid. We measured the Cohen‐Mansfield Agitation Inventory (CMAI) score at baseline and every two weeks.Results: Among 47 patients who entered the study, 25 completed the two phases. The median age for the 25 patients was 85.5 years. Analyses of the data of these 25 patients and of the patients <85 years‐old showed no significant differences in agitation level between the placebo and opioid phases. However, among the 13 patients who completed the study and were ≥85 years old, the agitation level at the end of the opioid phase was significantly lower than at the end of the placebo phase (mean change in CMAI score: −6.4; 95% confidence interval (CI): −10.96, −1.8). The decrease in agitation in the patients ≥85 years old persisted after adjusting for sedation. The results remained unchanged when we expanded the analyses to include four ≥85 patients who dropped out of the study after the second week of the opioid phase.Conclusion: Low dose, long‐acting opioids can lessen agitation that is difficult to control in very old (≥85) patients with advanced dementia. Copyright © 2003 John Wiley & Sons, Ltd.

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 (μg/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. Cancer 2001;92:3056–61. © 2001 American Cancer Society.

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. 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 μg/hour of fentanyl to 0.1 mg/hour of methadone was used to calculate the initial dose of methadone in all patients. 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. On the basis of this preliminary study, the authors suggest that when switching from intravenous fentanyl to methadone a conversion ratio of 25 μg/hour of fentanyl to 0.1 mg/hour of methadone may be safe and effective. Cancer 2001;92:1919–25. © 2001 American Cancer Society.