The intravenous to oral relative milligram potency ratio of morphine during chronic dosing in cancer pain.

Morphine (M) is the opioid analgesic of choice for severe cancer pain. The IV to PO M equipotent switch ratio (CR) is controversial. We designed this prospective observational cohort to confirm the efficacy and safety of M IV to PO CR of 1:3. Consecutive cancer patients admitted to an inpatient palliative medicine unit were screened for inclusion. Pain was managed by palliative medicine specialists. They were blinded to the patient data collected, and the calculated CR. The switch was considered successful if the following criteria were met: (1) Pain adequately controlled: pain rated as none or mild (2) Number of RD less than 4 (for non incident pain) per 24 hours (3) No limiting side effects. We used Day 3 ATC M dose for CR calculations. The major outcome measures were the IV : PO CR ratio, morphine doses (mg/day), pain severity, number of PRN doses, and day 1 and day 3side effects. Descriptive statistics were used to report mean, median, standard deviation and range of different variables. Two hundred and fifty six consecutive admissions were screened, and 106 were eligible for the study. Sixty two underwent a successful M route switch and were included in this analysis. A ratio of 1:3 was safely implemented over a wide M dose range. About 80% were successfully switched with a calculated CR of 1:3. 20% required an oral M dose adjustment after route switch either to better pain control or reduce side effects with a resultant higher (e.g. 1:4) or lower (e.g. 1:2) calculated potency ratios respectively. A potency ratio of 1:3 was safe as evaluated by common M side-effects, the dose also easy to calculate. The 1: 3 M IV to PO relative milligram potency ratio appears correct and practical for most patients over a wide M dose range.

Methylphenidate side effects in advanced cancer: a retrospective analysis.

INTRODUCTION: Methylphenidate (MP) is often recommended for symptom control in advanced cancer. Little is known about its side effects in frail adults. OBJECTIVES: To evaluate MP-associated symptoms or side effects (S/E). METHODS: Data was collected from 2 published prospective cohort series and a phase 2 study of MP for symptom control in advanced cancer. All 3 reports had identical dosing schedules and symptom assessments. Initial MP doses were 10 mg/d (5 mg at 8 AM and at 12 noon) titrated up to a maximum of 30 mg/d. Depression, fatigue, and symptoms identified as possible MP S/E were evaluated for presence (prevalence) and for severity (using categorical scales) before MP (day 0) and on days 3, 5, and 7 thereafter. The categorical scale used was none, mild, moderate, and severe. RESULTS: 62 patients were enrolled. Fifty completed 7 days of MP with a median age of 69 (range 30-90) years. Thirty-five received MP 10 mg/day. Most (96%) had improvement in depression and/or fatigue. Among the 62 patients, new symptom prevalence throughout the study was agitation (16%), insomnia (16%), dry mouth (15%), nausea (10%), tremors (6%), anorexia (5%), headache (3%), palpitations (2%), and vomiting (2%). Patients could have more than 1 symptom simultaneously. Seven (11%) withdrew due to MP S/E. Some symptoms present before MP showed significant improvement during MP therapy. CONCLUSIONS: (1) Treatment with MP (10-20 mg/d) in advanced cancer is well tolerated. (2) S/E symptoms with MP appeared to improve spontaneously despite continued MP therapy. (3) Depression and fatigue improved at doses lower than those recommended in other clinical conditions. (4) MP improved depression and fatigue, and some secondary symptoms associated with them. Methylphenidate (MP) appears safe when used in the treatment of depression and fatigue in advanced cancer.

Acute inpatient palliative medicine in a cancer center: clinical problems and medical interventions--a prospective study.

The clinical characteristics and medical interventions of the 100 consecutive cancer admissions to the acute care inpatient palliative medicine unit at the Cleveland Clinic for 2 months are described. Median age was 62 years (range, 31 to 92 years). The male-female ratio was 1:1. Most admissions were referred by hematology-oncology and had prior antineoplastic therapy. Reasons for admission were symptom control and cancer-related complications. Patients underwent invasive diagnostic and therapeutic procedures, hydration, transfusions, radiation, or chemotherapy, or a combination, during their admission. Most were discharged home with hospice care or had outpatient clinic follow-up. The mortality rate was 20%. Aggressive multidisciplinary management of symptoms, disease complications, comorbid conditions, and psychosocial problems were provided. Palliative medicine physicians provided continuity of care in the outpatient clinic and at home. An acute inpatient palliative medicine unit within a tertiary level medical center has a definable and important role in comprehensive cancer care.

Respiratory function during parenteral opioid titration for cancer pain.

BACKGROUND: Respiratory depression is the most feared opioid-related side-effect yet research on the topic is sparse. We evaluated changes in respiratory parameters during parenteral opioid titration for cancer pain to determine if opioid titration was associated with evidence of hypoventilation. The primary outcome measure was to measure changes in end-tidal CO(2) (ET-CO(2)) during opioid titration to pain control. METHODS: Subjects with severe cancer pain admitted for parenteral opioid titration for poorly controlled pain were eligible. Those who were oxygen dependent were excluded. ET-CO(2), O(2) saturation, respiratory rate (RR), and vital signs were monitored daily until pain control was achieved. RESULTS: 30 patients completed the study of which 29 are reported. The mean ET-CO(2) at initial evaluation was 33.39 -/+ 5.0 and 34.79 -/+ 5.7 mmHg at pain control (P =0.14, 95% CI -0.5 to 3.3). None had an ET-CO(2) > or =50 mmHg. All maintained O(2) saturation > or = 92%. RR dropped transiently below 10/minute in two subjects. CONCLUSIONS: Parenteral opioid titration for relief of cancer pain was not associated with respiratory depression as demonstrated by significant changes in ET-CO(2) or oxygen saturation in non-oxygen dependent cancer patients.

Symptom evaluation in palliative medicine: patient report vs systematic assessment.

PURPOSE: This study examined symptoms reported by patients after open-ended questioning vs those systematically assessed using a 48-question survey. MATERIALS AND METHODS: Consecutive patients referred to the palliative medicine program at the Cleveland Clinic Foundation were screened. Open-ended questions were asked initially followed by a 48-item investigator-developed symptom checklist. Each symptom was rated for severity as mild, moderate, or severe. Symptom distress was also evaluated. Data were collected using standardized pre-printed forms. RESULTS: Two hundred and sixty-five patients were examined and 200 were eligible for assessment. Of those assessed, the median age was 65 years (range 17-90), and median ECOG performance status was 2 (range 1-4). A total of 2,397 symptoms were identified, 322 volunteered and 2,075 by systematic assessment. The median number of volunteered symptoms was one (range zero to six). Eighty-three percent of volunteered symptoms were moderate or severe and 17% mild. Ninety-one percent were distressing. Fatigue was the most common symptom identified by systematic assessment but pain was volunteered most often. The median number of symptoms found using systematic assessment was ten (0-25). Fifty-two percent were rated moderate or severe and 48% mild. Fifty-three percent were distressing. In total, 69% of 522 severe symptoms and 79% of 1,393 distressing symptoms were not volunteered. Certain symptoms were more likely to be volunteered; this was unaffected by age, gender, or race. CONCLUSION: The median number of symptoms found using systematic assessment was tenfold higher (p<0.001) than those volunteered. Specific detailed symptom inquiry is essential for optimal palliation in advanced disease.

Strategies for pain management: cleveland clinic foundation guidelines for opioid dosing for cancer pain.

Pain remains the most common distressing symptom in advanced cancer. Opioids are the most effective drugs for pain currently available. Analgesia depends largely on appropriate administration. Cancer clinicians should be proficient in opioid pharmacotherapy. Although knowledge of general opioid dosing principles is helpful, in practice, complex clinical scenarios often arise, requiring more sophisticated and precise dosing maneuvers for which there is very little evidence-based literature. Familiarity with specific strategies indicated for common clinical problems provides a more focused approach and increases the likelihood of therapeutic success. This article enumerates cancer pain scenarios compiled from our palliative medicine practice and the opioid dosing strategies used by the palliative medicine department within the Cleveland Clinic Foundation.

Opioids in cancer pain: common dosing errors.

Many individuals with advanced malignancy continue to suffer from pain and, consequently, impaired quality of life. The clinical scenarios in advanced cancer pain are complex, and successful management may require a more sophisticated and individualized approach than suggested by the World Health Organization guidelines. In patients referred to the Harry R. Horvitz Center for Palliative Medicine in Cleveland, numerous commonly occurring errors in opioid use have been noted. This article describes these errors and offers strategies with which to improve outcomes for patients suffering with cancer pain.

Opioids, respiratory function, and dyspnea.

Dyspnea, the sensation of difficult breathing, is a common debilitating symptom in advanced cancer and chronic progressive cardiopulmonary disease. Primary treatment is correction of the underlying etiology. In incurable illness wherein the cause is irreversible and the goal is palliation, opioids are the drugs of choice for symptomatic relief. This article reviews current knowledge in the pathophysiology of dyspnea, proposed opioid mechanism of action, and evidence of efficacy.

The role of C-reactive protein as a prognostic indicator in advanced cancer.

C-reactive protein (CRP) is a nonspecific but sensitive marker of inflammation. Interleukin-6 (IL-6), IL-1, and tumor necrosis factor alpha induce the synthesis of CRP in hepatocytes. Increased CRP level is considered to be an important risk factor for atherosclerosis, myocardial infarction, peripheral vascular disease, and ischemic stroke. It is positively correlated with weight loss, anorexia-cachexia syndrome, extent of disease, and recurrence in advanced cancer. Its role as a predictor of survival has been shown in multiple myeloma, melanoma, lymphoma, ovarian, renal, pancreatic, and gastrointestinal tumors. Measurement of CRP is simple, cheap, and routine and provides valuable information in palliative care.