The successful use of parenteral methadone in a patient with a prolonged QTc interval.

Recent case reports have raised concerns about the potential for methadone to prolong the QTc interval (QT corrected for heart rate) and predispose patients to torsade de pointes (TdP), a life-threatening arrhythmia. We present a case report that describes the successful use of parenteral and oral methadone in a patient with uncontrolled cancer pain and a history of QTc prolongation. We describe an approach to the use of methadone in this patient and review both case reports and recent prospective studies that have evaluated the risk of TdP and the long-term outcome with respect to the development of TdP in patients receiving methadone for chronic pain or addiction.

Benefit-risk assessment of transdermal fentanyl for the treatment of chronic pain.

Transdermal fentanyl is effective and well tolerated for the treatment of chronic pain caused by malignancy and non-malignant conditions when administered according to the manufacturer's recommendations. Compared with oral opioids, the advantages of transdermal fentanyl include a lower incidence and impact of adverse effects (constipation, nausea and vomiting, and daytime drowsiness), a higher degree of patient satisfaction, improved quality of life, improved convenience and compliance resulting from administration every 72 hours, and decreased use of rescue medication. Transdermal fentanyl is a useful analgesic for cancer patients who are unable to swallow or have gastrointestinal problems. Transdermal fentanyl forms a depot within the upper skin layers before entering the microcirculation. Therapeutic blood levels are attained 12-16 hours after patch application and decrease slowly with a half-life of 16-22 hours following removal. Patients with chronic pain should be titrated to adequate relief with short-acting oral or parenteral opioids prior to the initiation of transdermal fentanyl in order to prevent exacerbations of pain or opioid-related adverse effects. Transdermal fentanyl can then be initiated based on the 24-hour opioid requirement once adequate analgesia has been achieved. The prolonged elimination of transdermal fentanyl can become problematic if patients develop opioid-related adverse effects, especially hypoventilation. Adverse effects do not improve immediately after patch removal and may take many hours to resolve. Patients who experience opioid-related toxicity associated with respiratory depression should be treated immediately with an opioid antagonist such as naloxone and closely monitored for at least 24 hours. Because of the short half-life of naloxone, sequential doses or a continuous infusion of the opioid antagonist may be necessary. Transdermal fentanyl should be administered cautiously to patients with pre-existing conditions such as emphysema that may predispose them to the development of hypoventilation. Transdermal fentanyl is indicated only for patients who require continuous opioid administration for the treatment of chronic pain that cannot be managed with other medications. It is contraindicated in the management of acute and postoperative pain, as pain may decrease more rapidly in these circumstances than fentanyl blood levels can be adjusted, leading to the development of life-threatening hypoventilation. Cognitive and physical impairments such as confusion and abnormal co-ordination can occur with transdermal fentanyl. Therefore, patients should be instructed to refrain from driving or operating machinery immediately following the initiation of transdermal fentanyl, or after any dosage increase. Patients may resume such activities once the absence of these potential adverse effects is documented.

Chordoid glioma: report of a case with unusual histologic features, ultrastructural study and review of the literature.

Chordoid gliomas are an uncommon primary brain tumor with histologic features of a chordoma and immunolabeling for glial fibrillary acid protein. We report the 32nd case with a review of the literature. The clinical, radiographic and pathologic features of the tumor are presented with new pathologic findings adding support that this lesion may be of ependymal origin. Treatment and long term outcome are limited but chordoid gliomas appear to be indolent lesions that may be cured with gross total resection.

Intraventricular morphine administration for control of chronic cancer pain.

Twenty cancer patients with severe chronic pain have been treated with intraventricular morphine sulfate. Adequate pain relief until death was achieved in 10 patients; 1 patient has been treated for 9 months and is still being treated. In 2 patients, the effects of the morphine sulfate on their unilateral pelvic pain wore off after 4 and 6 months because of tumor progression. At that time, they underwent chordotomy procedures elsewhere. The treatment was discontinued in 4 patients for reasons other than inadequate pain relief, such as medical complications or resolution of pain. In 3 patients, the procedure was abandoned when emotional and psychological factors interfered with pain control. Dose requirements of intraventricular morphine sulfate varied greatly, depending on the total daily dose of systemic narcotic intake at the onset of the study. Intraventricular morphine sulfate is a feasible and reliable method to achieve pain relief in selected cancer patients with severe chronic pain when the maximum tolerated dose of systemic narcotic analgesics has become insufficient to control their pain.