Suresh K. Reddy

Palliative Care Inpatient Service in a Comprehensive Cancer Center: Clinical and Financial Outcomes

PURPOSE Inpatient palliative care units are unavailable in most cancer centers and tertiary hospitals. The purpose of this article is to review the outcomes of the first 344 admissions to the Palliative Care Inpatient Service (PCIS) at our comprehensive cancer center. PATIENTS AND METHODS We retrospectively reviewed our computerized database for clinical and demographic information, length of stay, and hospital billing during the first year of the services operation. RESULTS Three hundred twenty patients were admitted during the study period. Their median age was 57 years. The main cancer diagnoses were thoracic or head and neck (44%), gastrointestinal (25%), and hematologic malignancy (8%). The main referral symptoms were pain (44%), nausea (41%), fatigue (39%), and dyspnea (38%). The median length of stay in the PCIS was 7 days (range, 1 to 58 days). Fifty-nine patients died while in the PCIS. However, the overall hospital mortality rate was not increased compared with that in the year before the establishment of the PCIS (3.58% v 3.59%). The mean reimbursement rate for all palliative care charges was approximately 57%, and the mean daily charges in the PCIS were 38% lower than the mean daily charges for the rest of the hospital. Symptom intensity data showed severe distress on admission and significant improvement in the main target symptoms. Most patients were discharged to a hospice. CONCLUSION The PCIS has been accepted in our tertiary cancer center on the basis of its clinical utility and financial viability.

Reduction of Cancer-Related Fatigue With Dexamethasone: A Double-Blind, Randomized, Placebo-Controlled Trial in Patients With Advanced Cancer

PURPOSE Cancer-related fatigue (CRF) is the most common symptom in patients with advanced cancer. The primary objective of this prospective, randomized, double-blind, placebo-controlled study was to compare the effect of dexamethasone and placebo on CRF. PATIENTS AND METHODS Patients with advanced cancer with ≥ three CRF-related symptoms (ie, fatigue, pain, nausea, loss of appetite, depression, anxiety, or sleep disturbance) ≥ 4 of 10 on the Edmonton Symptom Assessment Scale (ESAS) were eligible. Patients were randomly assigned to either dexamethasone 4 mg or placebo orally twice per day for 14 days. The primary end point was change in the Functional Assessment of Chronic Illness-Fatigue (FACIT-F) subscale from baseline to day 15. Secondary outcomes included anorexia, anxiety, depression, and symptom distress scores. RESULTS A total of 84 patients were evaluable (dexamethasone, 43; placebo, 41). Mean (± standard deviation) improvement in the FACIT-F subscale at day 15 was significantly higher in the dexamethasone than in the placebo group (9 [± 10.3] v 3.1 [± 9.59]; P = .008). The improvement in FACIT-F total quality-of-life scores was also significantly better for the dexamethasone group at day 15 (P = .03). The mean differences in the ESAS physical distress scores at day 15 were significantly better for the dexamethasone group (P = .013, respectively). No differences were observed for ESAS overall symptom distress (P = .22) or psychological distress score (P = .76). Frequency of adverse effects was not significantly different between groups (41 of 62 v 44 of 58; P = .14). CONCLUSION Dexamethasone is more effective than placebo in improving CRF and quality of life in patients with advanced cancer.

Characteristics and correlates of dyspnea in patients with advanced cancer

BACKGROUND Dyspnea is a very distressing symptom present in the vast majority of patients with advanced cancer. There are limited data on the characteristics and correlates of dyspnea in this population. The purpose of this study was to characterize dyspnea, explore the differences between breakthrough and continuous presentations, and to determine factors associated with its intensity. METHODS Prospective observational study among 70 patients with dyspnea referred to a palliative care service. Dyspnea was assessed using the Edmonton Symptom Assessment System (ESAS, 0-10) and the Oxygen Cost Diagram (OCD). Oximetry, pulmonary function tests, Hospital Anxiety and Depression Scale (HADS), and a detailed systematic evaluation of daily characteristics of dyspnea were performed. Other symptoms were recorded using the ESAS. RESULTS Of 30 patients, 70 (43%) were female, median age was 58 (range, 28-87), and the most frequent cancer diagnosis were lung (31/70; 44%) and urologic (15/70; 21%). Constant dyspnea occurred in 27 of 70 (39%) patients, with 14 of 70 (20%) presenting breakthrough episodes. Breakthrough-only dyspnea occurred in 43 of 70 (61%). The majority of patients with breakthrough episodes (39/57; 68%) presented fewer than 5 episodes daily, most frequently lasting for less than 10 minutes (50/57; 88%). In univariate analyses ESAS dyspnea was associated with fatigue (p < 0.0001), sleep (p = 0.002), anxiety (p = 0.006), depression (p = 0.01), sensation of well-being (p = 0.03), and with OCD (p = 0.001). In multivariate analysis, ESAS dyspnea was associated with fatigue (p = 0.001), forced expiratory volume (p = 0.004), pain (p = 0.01), and depression (p = 0.03). Dyspnea intensity significantly interfered with activities (general activity, p = 0.01, mood, p = 0.02, walking ability, p = 0.04, normal work p = 0.04, and enjoyment of life, p = 0.01). CONCLUSION Dyspnea in patients with advanced cancer more frequently had breakthrough characteristics, was of very short duration, and interfered with daily activities.

The neuroleptics as adjuvant analgesics

The role of neuroleptic drugs as adjuvant analgesics has been a subject of longstanding controversy. Despite frequent claims of efficacy, evidence from controlled trials supports neither claims of intrinsic analgesic properties nor the routine use of the neuroleptics as a means to reliably induce clinically useful analgesia. Methotrimeprazine is unique in that there is evidence for reliable dose-related analgesia that is comparable to opioid-mediated analgesia, although routine use is not recommended. Despite probable interaction with opioid receptors, there is insufficient evidence to support a role for the butyrophenone category of neuroleptics as adjuvant analgesics. Limited trials of the neuroleptics may be considered for pain that has been unresponsive to more conventional pharmacologic approaches, especially when associated with headache, nerve injury, or psychological distress. The neuroleptics have an important role in the symptomatic management of agitation, delirium, and nausea, particularly in patients with cancer.

The benzodiazepines as adjuvant analgesics

There has been long-standing debate regarding whether benzodiazepines possess analgesic properties that are independent of their effects on mood and alertness. A careful review of the literature reveals insufficient evidence to support the contention that the benzodiazepines have meaningful analgesic properties in most clinical circumstances. Treatment with the benzodiazepines may reduce complaints of pain, but this seems to be an indirect effect related to their psychotropic properties, such as alleviation of anxiety and, in selected cases, depression. In the absence of definitive data, clinical experience suggests a potential role for treatment with benzodiazepines for acute muscle spasm, concomitant chronic pain and anxiety, and lancinating neropathic pain, in which case clonazepam and alprazolam may be the agents of choice. They should probably not be considered as first-line choices even for the above indications, since potential benefits must be considered in the context of potential for the development of cognitive impairment, physical and psychological dependence, worsening depression, overdose, and other side effects.

The Effect of Oral Methadone on the QTc Interval in Advanced Cancer Patients: A Prospective Pilot Study

BACKGROUND Recent reports suggest that high doses of methadone may prolong QTc interval and occasionally cause torsades de pointes; however, few of these studies involved the palliative care population. OBJECTIVE The purpose of this study was to determine the effect of initiation of methadone on QTc interval in patients with cancer pain seen at the palliative care setting. METHODS We enrolled 100 patients with cancer in this prospective study. Patients were followed clinically and electrocardiographically for QTc changes at baseline, 2, 4, and 8 weeks. Contributing factors for QTc prolongation such as medications, cardiovascular diseases, and electrolytes disturbances were documented. QTc prolongation was defined as greater than 430 ms in males and greater than 450 ms in females, and significant QTc prolongation was defined as QTc interval greater than 25% increase from baseline or 500 ms or more. RESULTS Electrocardiographic (ECG) assessments were available for 100, 64, 41, and 27 patients at baseline, 2-, 4-, and 8-week follow-up, respectively. At baseline prior to initiation of methadone, 28 (28%) patients had QTc prolongation. Clinically significant increase in QTc occurred in only 1 of 64 (1.6%) patients at week 2, and none at weeks 4 and 8. There was no clinical evidence of torsades de pointes, ventricular fibrillation, or sudden death. QTc prolongation was more frequent among patients with increased baseline QTc interval. CONCLUSIONS Baseline QTc prolongation was common, whereas significant QTc interval 500 ms or more after methadone initiation rarely occurred, with no evidence of clinically significant arrhythmias. This study supports the safety of methadone use for pain control in patients with advanced cancer in the palliative care setting.

Pain and Loss of Function in Head and Neck Cancer Survivors

Head and neck cancers are relatively uncommon malignancies and the characteristics of pain and functional impairments in survivors are not well studied. To characterize the incidence, location, severity, types and causes of pain; associated functional impairments, and pain management methods, the medical charts of 40 consecutive outpatients with biopsy-proven head and neck cancers were reviewed. Pain was severe in 52% (N = 21), and was located near sites of tumor origin. Pain was caused by tumor recurrence in 35% (N = 14), treatment sequelae in 30% (N = 12), multiple etiologies in 25% (N = 10), and unrelated causes in 10% (N = 4). Pains were mixed nociceptive and neuropathic pain in 37.5% (N = 15), nociceptive pain in 32.5% (N = 13), myofascial in 13.0% (N = 6), neuropathic in 7.5% (N = 3); and other mixed types in 7.5% (N = 3). Despite the high prevalence of dysphagia (82%), 60% used orally administered opioid-nonopioid analgesics. Physical disfigurement (87.5%; N = 35), dysphagia (62.5%, N = 25), and jaw dysfunction (40.0%; N = 16) were the most frequent physical impairments. Multiple regression analysis showed that the presence of skull base or mandibular bone involvement had significant influence on the severity of pain (P = 0.03, adjusted R2 0.25) We conclude that pain in head and neck cancer can be chronic, severe, and persistent despite completion of oncologic treatment.

Clinical Signs of Impending Death in Cancer Patients

BACKGROUND The physical signs of impending death have not been well characterized in cancer patients. A better understanding of these signs may improve the ability of clinicians to diagnose impending death. We examined the frequency and onset of 10 bedside physical signs and their diagnostic performance for impending death. METHODS We systematically documented 10 physical signs every 12 hours from admission to death or discharge in 357 consecutive patients with advanced cancer admitted to two acute palliative care units. We examined the frequency and median onset of each sign from death backward and calculated their likelihood ratios (LRs) associated with death within 3 days. RESULTS In total, 203 of 357 patients (52 of 151 in the U.S., 151 of 206 in Brazil) died. Decreased level of consciousness, Palliative Performance Scale ≤20%, and dysphagia of liquids appeared at high frequency and >3 days before death and had low specificity (<90%) and positive LR (<5) for impending death. In contrast, apnea periods, Cheyne-Stokes breathing, death rattle, peripheral cyanosis, pulselessness of radial artery, respiration with mandibular movement, and decreased urine output occurred mostly in the last 3 days of life and at lower frequency. Five of these signs had high specificity (>95%) and positive LRs for death within 3 days, including pulselessness of radial artery (positive LR: 15.6; 95% confidence interval [CI]: 13.7-17.4), respiration with mandibular movement (positive LR: 10; 95% CI: 9.1-10.9), decreased urine output (positive LR: 15.2; 95% CI: 13.4-17.1), Cheyne-Stokes breathing (positive LR: 12.4; 95% CI: 10.8-13.9), and death rattle (positive LR: 9; 95% CI: 8.1-9.8). CONCLUSION We identified highly specific physical signs associated with death within 3 days among cancer patients.

Unrelieved Pain and Suffering in Patients With Advanced Cancer

Even with specialist-level palliative care, cancer pain can be difficult to treat especially when the pain is complicated by profound suffering. It is paramount to consider not only the patients’ biochemical factors but also their psychosocial and spiritual/existential influences. A multidimensional approach with knowledge of the risk factors for poor pain control is important to prevent, detect, and manage risk factors for intractable pain, including psychosocial distress, addictive behavior, and delirium in patients with terminal cancer. We present 3 cases of patients with advanced cancer with intractable bone pain whose hospital courses were complicated by severe psychosocial distress and delirium. We also propose an algorithm of multidimensional approach to unrelieved pain and suffering in patients with advanced cancer.

Psoas sheath chemical neurolysis for management of intractable leg pain from metastatic liposarcoma

CASE REPORT A 56-year-old man with widely metastatic liposarcoma, after left Tower extremity amputation, complained of severe right lower extremity pain. Trials of systemic opioids had resulted in poor pain control while introducing intolerable dose-limiting side effects. METHODS AND RESULTS Initial inpatient management consisted of a lumbar epidural infusion of a dilute local anesthetic and preservative-free morphine. This provided satisfactory relief but was discontinued because of recrudescence of phantom limb pain. A lumbar epidural infusion of preservative-free morphine sulfate was associated with poor pain relief, central nervous system (CNS) side effects, and severe urinary retention resulting in acute renal failure. A repeated trial of parental opioids provided marginal pain relief with persistent CNS side effects. Chemical neurolysis of the lumbar plexus was performed with 10 ml of 10% aqueous phenol injected into the psoas muscle sheath. The pain gradually resolved over a 2-day period without apparent side effects. Motor function was preserved, pain was resolved, and as systemic opioids were reduced, cognitive function and overall well-being were improved.