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Biomedical subjects

Paolo L Manfredi

Publications and source records attributed to Paolo L Manfredi.

14 recordsLinked to original sources
PubMed2003

A safe and effective method for converting patients from transdermal to intravenous fentanyl for the treatment of acute cancer-related pain.

BACKGROUND: The delayed effects (12-16 hours) of transdermal fentanyl make dose titration difficult during acute exacerbations of cancer pain. Patients at the authors' institution routinely are switched from transdermal to intravenous (IV) fentanyl using a 1:1 (transdermal:IV) conversion during severe episodes of pain. METHODS: The authors evaluated nine consecutive hospitalized patients with cancer who had severe pain for up to 6 days following the conversion from transdermal to IV fentanyl. Pain intensity was rated using an 11-point (0-10) verbal numeric rating scale (NRS). All 9 patients initially reported their pain intensity with movement as >or= 8 during treatment with transdermal fentanyl. Eight patients initially reported their pain at rest as >or= 8. In each patient, all transdermal patches were removed, and a continuous infusion (CI) delivering IV fentanyl at the same hourly rate was initiated simultaneously. Demand boluses of IV fentanyl equivalent in dosage to 50-100% of the CI rate remained available by patient-controlled analgesia (PCA). Pain intensity (0-10), sedation (0-3), and hourly fentanyl requirements (micrograms per hour) were assessed and recorded immediately prior to patch removal and at least once daily after the initiation of IV fentanyl. The CI and demand boluses were titrated whenever necessary on the basis of pain intensity and supplemental PCA use. RESULTS: All 9 patients reported mild levels (<or= 4) of pain at rest within 5 days. The median time to achieve mild levels of pain at rest was 1.5 days. Six patients achieved mild levels of pain with movement within 3 days. Three patients never achieved mild levels of pain with movement while receiving IV fentanyl. No serious side effects were reported. CONCLUSIONS: The conversion from transdermal to IV fentanyl can be accomplished safely and effectively using a 1:1 (transdermal:IV) conversion during acute exacerbations of cancer pain.

Administration, Cutaneous↗
PubMed2003

Opioid treatment for agitation in patients with advanced dementia.

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 > or =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 > or =85 years old persisted after adjusting for sedation. The results remained unchanged when we expanded the analyses to include four > or =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 (> or =85) patients with advanced dementia.

Aged↗
PubMed2003

QTc interval prolongation associated with intravenous methadone.

Numerous medications prolong the rate-corrected QT (QTc) interval and induce arrhythmias by blocking ionic current through cardiac potassium channels composed of subunits expressed by the human ether-a-go-go-related gene (HERG). Recent reports suggest that high doses of methadone cause torsades de pointes. To date, no controlled study has described an association between methadone and QTc prolongation. The only commercial formulation of parenteral methadone available in the United States contains the preservative chlorobutanol. The objectives of this study are to determine: (1) whether the administration of intravenous (i.v.) methadone causes QTc prolongation in humans; (2) whether methadone and/or chlorobutanol block cardiac HERG potassium currents (IHERG) in vitro. Over 20 months, we identified every inpatient with at least one electrocardiogram (ECG) performed on i.v. methadone. For each patient, we measured QTc intervals for every available ECG performed on and off i.v. methadone. Concurrent methadone doses were also recorded. Similar data were collected for a separate group of inpatients treated with i.v. morphine. In a separate set of experiments IHERG was evaluated in transfected human embryonic kidney cells exposed to increasing concentrations of methadone, chlorobutanol, and the two in combination. Mean difference (+/- standard error) per patient in QTc intervals on and off methadone was 41.7 (+/- 7.8)ms, p<0.0001. Mean difference in QTc intervals on and off morphine was 9.0 (+/- 6.1)ms, p=0.15. The approximately linear relationship between QTc measurements and log-dose of methadone was significant (p<0.0001). Methadone and chlorobutanol independently block IHERG in a concentration-dependent manner with IC50 values of 20 +/- 2 microM and 4.4 +/- 0.3 mM, respectively. Chlorobutanol potentiates methadone's ability to block IHERG. Methadone in combination with chlorobutanol is associated with QTc interval prolongation. Our data strongly suggest that methadone in combination with chlorobutanol is associated with QTc interval prolongation.

Cell Line↗
PubMed2003

Pain assessment in elderly patients with severe dementia.

The purpose of this study was to assess the reliability and validity of facial expressions as pain indicators in patients with severe dementia. Based on interviews with patients who could report pain, we defined characteristics of decubitus ulcers associated with reports of pain during dressing changes. We then evaluated 9 patients who had ulcers with these characteristics but were unable to communicate verbally because of severe dementia. We videotaped their facial expressions before and during their decubitus ulcer dressing change. We showed the videotape segments, in random order, to 8 medical students and 10 nurses. The 18 viewers were asked to infer the presence or absence of pain based on their observations of the patients' facial expressions and vocalizations. The dressing change of decubitus ulcers extending beyond the subcutaneous tissue, covering an area of at least 9 cm(2), and with a moist surface, was always reported as painful by study patients able to report (95% confidence interval of 69-100%). The intraclass correlation coefficient for the answers of the 18 viewers evaluating each videotape segment for the presence of pain was 0.64. Sensitivity, specificity, and positive and negative predictive values of viewers' ratings of facial expressions and vocalizations as a measure of the presence of pain were: 0.70, 0.83, 0.90, and 0.81. The intraclass correlation coefficient for the answers rating pain intensity was only 0.10, indicating only slight agreement beyond chance. Assuming dressing changes of ulcers reported as painful by communicative patients are also painful in non-verbal severely demented patients, clinician observations of facial expressions and vocalizations are accurate means for assessing the presence of pain, but not its intensity, in patients unable to communicate verbally because of advanced dementia.

Aged↗
PubMed2003

Central pain in cancer patients.

The prevalence of pain caused by injury to the central nervous system (CNS), or central pain (CP), in cancer patients is unknown. In order to define prevalence and characteristics of central pain in hospitalized patients with cancer, we performed a retrospective review of medical records of patients evaluated by 2 different services: the Pain Service and the Neurology Service, at Memorial Sloan-Kettering Cancer Center. The prevalence of CP in these patients was 4% and 2%, respectively. Primary and metastatic tumors and their therapy, including surgery, radiation and chemotherapy, were all potential causes of CP. The occurrence of CP in patients with primary CNS tumors was higher in patients with spinal cord tumors compared to patients with brain tumors (P <.0001).

Adult↗
PubMed2003

Neuropathic pain in patients with cancer.

We provide a detailed description of painful neural lesions in hospitalized patients with cancer. A total of 187 consecutive patients with cancer and pain, referred to the pain service of a cancer hospital, were evaluated within 24 hours by two neurologists and followed until discharge or death. Based on history, pain descriptors, physical examination, and radiological and electrophysiological studies, the pain was categorized as neuropathic in 103 patients. The most frequent sites of neurological injury were nerve roots, spinal cord and cauda equina, brachial and lumbosacral plexus, and peripheral nerves. There were no patients with pain caused by injury to the brain. In 93 of these patients, the pain was caused by ongoing neural injury, while, in 10 patients, the neural injury was old and stable. Within these two groups of patients with neuropathic pain, analgesic treatments differed. Prospective studies may determine if categorizing painful neurological injuries in cancer patients based on inferred pathophysiology is useful when deciding among different treatment options.

Adolescent↗
PubMed2002

Pitfalls of opioid rotation: substituting another opioid for methadone in patients with cancer pain.

The successful use of methadone in cancer pain has been supported by numerous case reports and clinical studies. Methadone is usually used as a second or third line opioid medication. As the use of methadone increases we are facing the challenge of converting methadone to other opioids as part of sequential opioid trials. Data on the equianalgesic ratios for the substitution of other opioids for methadone are lacking. We present prospective data on 13 consecutive rotations from methadone to a different opioid. The opioid rotation was followed by escalation of pain and/or severe dysphoria, not controlled by a rapid increase in the dose of the second opioid, in 12 of the 13 patients. Only one patient was successfully maintained on the second opioid after the discontinuation of methadone, while 12 patients required a switch back to methadone. We conclude that opioid rotation from methadone to another opioid is often complicated by worsening pain and dysphoria. These symptoms may not improve despite upward titration of the second opioid. A uniformly accepted conversion ratio for substituting methadone with another opioid is currently not available. More data on the rotation from methadone to other opioids are needed.

Adult↗
PubMed2002

Influence of opioid agonists on cardiac human ether-a-go-go-related gene K(+) currents.

We have evaluated the ability of various opioid agonists, including methadone, L-alpha-acetylmethadol (LAAM), fentanyl, meperidine, codeine, morphine, and buprenorphine, to block the cardiac human ether-a-go-go-related gene (HERG) K(+) current (I(HERG)) in human cells stably transfected with the HERG potassium channel gene. Our results show that LAAM, methadone, fentanyl, and buprenorphine were effective inhibitors of I(HERG), with IC(50) values in the 1 to 10 microM range. The other drugs tested were far less potent with respect to I(HERG) inhibition. Compared with the reported maximal plasma concentration (C(max)) after administration of therapeutic doses of these drugs, the ratio of IC(50)/C(max) was highest for codeine and morphine (>455 and >400, respectively), thereby indicating that these drugs have the widest margin of safety (of the compounds tested) with respect to blockade of I(HERG). In contrast, the lowest ratios of IC(50)/C(max) were observed for LAAM and methadone (2.2 and 2.7, respectively). Further investigation showed that methadone block of I(HERG) was rapid, with steady-state inhibition achieved within 1 s when applied at its IC(50) concentration (10 microM) for I(HERG) block. Results from "envelope of tails" tests suggest that the majority of block occurred when the channels were in the open and/or inactivated states, although approximately 10% of the available HERG K(+) channels were apparently blocked in a closed state. Similar results were obtained for LAAM. These results demonstrate that LAAM and methadone can block I(HERG) in transfected cells at clinically relevant concentrations, thereby providing a plausible mechanism for the adverse cardiac effects observed in some patients receiving LAAM or methadone.

Cation Transport Proteins↗