Palliation of Intractable Cancer-Related Pain With Low-Dose Epidural Bupivacaine.

Introduction: Patients with advanced cancer nearing end of life often present with complex multifactorial pain. Although epidural analgesia is routinely used in inpatient hospital settings for targeted pain control, there is scant description in the literature of the use of low-dose epidural analgesia for relief of cancer-related pain at end of life. In this study, we present a case of difficult to control cancer-related rectal and pelvic pain in a patient who responded well in her last days of life to a low-dose bupivacaine epidural. Case Description: A 66-year-old woman presented for inpatient hospital admission for pain control from home hospice with intractable cancer-related pain from metastatic colorectal adenocarcinoma marked by extensive erosive lesions extending from the anterior perineum to the posterior rectum, with rectovaginal fistula. The patient reported poor tolerance of medications and described spiritual beliefs (based in Buddhism) that caused her and her family to prioritize maintaining a lucid, clear mind above nearly all else while seeking symptom management. The patient was so debilitated by pain at the time of presentation that she was bedbound in a quadruped position. Case Management and Outcome: After 2 weeks of poor pain control in the hospital with multiple failed attempts at palliation-including bilateral pudendal block, as well as opioids and other routine, but potentially sedating or deliriogenic, medications to treat her pain-the patient permitted administration of a low-dose bupivacaine epidural that significantly reduced her pain and allowed the patient to remain clear-headed up until the time of her death. Twenty-three days after admission, and 5 days after initiation of low-dose bupivacaine epidural for pain control, the patient died peacefully in the hospital. Conclusion: Low-dose epidural analgesia for cancer-related pain at end of life from malignancy involving the pelvis-perineum, rectum, or vagina-may be a viable option for patients, particularly those who wish to avoid the risk of somnolence or confusion from systemic opioids and other analgesics.

Use of Fosaprepitant for Management of Suspected Antimicrobial-Associated Nausea: A Case Report.

Intractable nausea can occur in numerous settings. We report on a 49-year-old woman with a past medical history of cystic fibrosis (CF) with chronic hypoxia, chronic nausea, complex infection history and frequent hospitalizations who was admitted to an academic medical center with a CF exacerbation. Her chronic nausea worsened with the use of antimicrobials, and she was unable to tolerate dopamine or serotonin antagonist antiemetics. Nausea persisted despite the use of benzodiazepines and antihistamines. She was given a one-time dose of fosaprepitant 150 mg intravenously (IV) with marked improvement of her nausea. During subsequent exacerbations, she again developed severe nausea which continued to respond well to a one-time dose of fosaprepitant 150 mg IV. Fosaprepitant is a substance P/neurokinin-1 (NK1) receptor antagonist that is FDA-approved for the prevention of chemotherapy-induced nausea and vomiting and has been used to prevent post-operative nausea and vomiting. Its use in other contexts has not been well established. This case suggests a role for fosaprepitant in the management of nausea outside the context of chemotherapy or general anesthesia.

Development and validation of a performance-based palliative care assessment tool for student pharmacists.

INTRODUCTION: Integration of hospice and palliative care principles within pharmacy curricula is essential to fill the need of pharmacist training in this growing specialty. A formalized assessment tool to evaluate skill development does not exist for student pharmacists specific to palliative care. The objective of this study was to develop a valid and reliable, palliative care-focused, performance-based assessment tool for student pharmacists. METHODS: Eight academic palliative care (PC) pharmacists were recruited for the workgroup to perform domain development, validation, tool creation, and reliability testing for this performance-based assessment tool. Hospice and palliative care clinical pharmacist entrustable professional activities (EPAs) served as the framework. Content validity testing utilized content validity index and scale universal agreement (S-CVI/UA) to determine level of agreement for activities included in the tool. Student volunteers completed a standardized patient case and workgroup members served as raters during the reliability testing phase. Interrater reliability was measured through calculation of Fleiss Kappa scores for each activity. RESULTS: Out of 14 EPAs, nine were deemed "essential" to include in the tool. Thirty-four supporting activities for the nine essential EPAs were drafted. Two rounds of content validity testing were necessary to achieve S-CVI/UA of 0.9593. Consensus was reached from workgroup members for activities deemed necessary to include in the tool after questionnaire distribution utilizing a Fleiss Kappa cutoff >0.6. CONCLUSIONS: This validated tool will afford colleges and schools of pharmacy with PC curricula an opportunity to assess student achievement of PC-specific skills and evaluate curricular effectiveness.

A Specialist Palliative Pharmacist Enriches the Interdisciplinary Team: A Case Series Discussion Illustrating the Entrustable Professional Activities for Specialist Hospice and Palliative Care Pharmacists.

Introduction: Palliative care (PC) pharmacists are an integral member of the PC team. Essential roles have been defined and entrustable professional activities (EPAs) have been recently developed for hospice and PC pharmacists. Case Description: We review four different complex patient cases where the specialist PC pharmacist worked with the interdisciplinary team to address whole patient suffering. Through the case series, we highlight the various components of HAPC pharmacist EPAs across the continuum of care. Case Management, Outcome, and Conclusion: Through the case series discussion, we brought to light PC pharmacists' EPAs in pharmacotherapy consultation, assessing and optimizing medication therapy, symptom management, deprescribing, participating in goals-of-care discussions, managing medication therapy in the withdrawal of life-sustaining therapy in collaboration with interdisciplinary team in alignment with patient and family values, prognosis, and plan of care. We also emphasized the importance of PC pharmacists contributing to the advancement of science.

Comparing National Methadone Equianalgesic Tools.

Methadone is an effective analgesic with unique pharmacokinetic and pharmacodynamic variables. There is no national consensus on methadone equianalgesia tools. Our study aimed to compare methadone equianalgesic tools from various national institutions with the primary objective to summarize current practice and secondary objective to determine if a national consensus can be established. Out of 25 institutional methadone equianalgesic tools reviewed, 18 contained sufficient data and were included in this study. Fifteen (15) of the institution evaluated tools utilized a wide variety of dose-dependent modalities for methadone conversion with the hospice and palliative care (HAPC) Consensus method being the most common. Based on the variability of the equianalgesia tools evaluated in this study, we were unable to recommend a consensus methadone conversion method. Further trials exploring methadone equianalgesia beyond our study are needed.

A National Survey of Institutional Guidelines for the Use of Ketamine, Lidocaine, and Dexmedetomidine for Refractory Pain.

Background: Although opioids are used first line for cancer pain and commonly for complex noncancer pain, there are risks associated with their use and not effective for all types of pain. There's a need to identify and develop clinical practice guidelines for nonopioids for the treatment of refractory pain. Methods: Our study collected information from national clinical practice guidelines for ketamine, lidocaine, and dexmedetomidine with the aim to identify consensus among the different practices. Results: Fifteen institutions nationally participated in the study and only nine of those institutions had guidelines and were permitted by their health system to share them. Of the institutions that participated, 44% had guidelines for ketamine and lidocaine, and only two institutions (22%) had guidelines for ketamine, lidocaine, and dexmedetomidine for refractory pain. There were variations in restriction of the level of care and prescribers, dosing, and determination of efficacy. There were trends of consensus in monitoring for side effects. Conclusion: This study serves as a starting point for a snapshot of the use of ketamine, lidocaine, and dexmedetomidine for refractory pain, but further studies and increased participation of institutions are needed to develop consensus clinical practice guidelines.

Chlorpromazine's Potential Role in Palliating Distressing Symptoms Associated With Hyperactive Delirium in Patients at End of Life.

Background: The hyperactive subtype of delirium is characterized by agitation, restlessness, delusions, and/or hallucinations, which commonly present near end of life (EoL). Symptom relief often requires the use of medications, such as chlorpromazine (CPZ), to reduce patient distress by inducing proportional sedation. Objective: The purpose of this study was to evaluate CPZ's potential role in managing the distress of hyperactive delirium in patients receiving EoL care. Methods: A retrospective observational study among hospitalized patients with advanced cancer at EoL between January 2020 to December 2021. Results: Sustained improvement in symptoms of delirium was seen in 80% of patients as identified in the palliative psychiatrist's progress notes. Meanwhile, 75% of patient's improvement was reported in nursing-driven Delirium Observation Screening Scale. Conclusion: This study elucidates that at doses of ∼100 mg/day, CPZ is potentially an effective medication for patients with advanced cancer, experiencing hyperactive delirium in their final week of life.

Dexmedetomidine Continuous Infusion for Refractory Cancer Pain at End of Life: A Case Report.

Refractory cancer-related pain at end-of-life (EoL) is multifaceted and may require utilizing medications with different mechanism of actions beyond opioids. We report the successful use of dexmedetomidine in a 63-year old female with recurrent breast cancer and intractable left arm pain and swelling admitted to University of California, San Diego, Health (UC San Diego Health), palliative care unit. Patient's pain and agitation continued to persist and she declined clinically despite efforts to start methadone, continuous infusion opioids, continuous infusion lidocaine and intravenous chlorpromazine by the palliative care team. On hospital day (HD) 11 patient was started on dexmedetomidine continuous infusion for refractory pain per our protocol at UC San Diego Health. The next day the patient appeared much improved in terms of pain and agitation with grimacing and moaning completely resolved. She was able to have some lucid periods and interacting with her family. With the addition of dexmedetomidine to her pain regiment, the patient was able to peacefully die 5 days later. This case report highlights the clinical utility of demedetomidine in a palliative care unit for refractory pain at EoL.

A Comparison of Institutional Opioid Equianalgesia Tools: A National Study.

Context: Equianalgesic tools are commonly utilized to guide dose of analgesic therapy, but there is no national consensus on equianalgesic calculations in the United States. Objectives: To propose a summary of current opioid equianalgesic data that include variations and trends among national institutions. Methods: Opioid equianalgesic tools were obtained between May and September 2021. For meperidine, tramadol, codeine, hydrocodone, morphine, oxycodone, oxymorphone, hydromorphone, levorphanol, fentanyl, and tapentadol, details of adjustment for incomplete tolerance, opioid equianalgesic ratios, and formulation types were collected and analyzed. Baseline opioid pharmaco kinetic data were obtained through manufacturer labels on FDA databases, including half-life (T1/2), volume of distribution (Vd), clearance (Cl), area under the curve (AUC), max concentration (Cmax), and time to max concentration (Tmax). Results: Thirty-two institutions' equianalgesic tools were included with each study opioid appearing on an average of 23 institutions' tools. Few tools contained guidance on levorphanol or tapentadol; or included minimum and maximum recommended doses. All tools included guidance on fentanyl, hydromorphone, oxycodone, morphine, and hydrocodone. A minority of tools included guidance on cross-tolerance considerations (n = 12, 37.5%). Oral-tramadol-to-oral-morphine and oral-hydromorphone-to-intravenous (IV)-hydromorphone had the largest variances across equianalgesic tools (6.7 ± 2.8 and 4.06 ± 1.2 mg, respectively). Conclusion: Opioid equianalgesia tools from across the United States demonstrated significant variation in their inclusion of guidance on adjustment for incomplete cross-tolerance, oral-to-IV, and oral-to-oral opioid equianalgesic ratios, and which opioids and formulations were listed. Tramadol and hydromorphone had the most variation in their equianalgesic guidance among the opioids.

Development of Entrustable Professional Activities for Specialist Hospice and Palliative Care Pharmacists.

CONTEXT: Entrustable professional activities (EPAs) translate competencies into explicit, practical terms that clearly state the expected roles and responsibilities of clinicians who have achieved proficiency and expertise in a field. EPAs are defined for Hospice and Palliative Medicine physicians but not for other members of Hospice and Palliative Care (HAPC) interprofessional teams, including pharmacists. OBJECTIVES: The objective of this study was to develop EPAs for HAPC pharmacists. METHODS: An 11-member workgroup of HAPC pharmacists was convened to develop candidate EPAs using nominal group and modified-Delphi methods. Content validity index was used as a measure of consensus, defined a priori at ≥ 60%. Vetting occurred via intra- and interprofessional stakeholder reactor groups and a national survey of HAPC pharmacists. RESULTS: Following an iterative process of workgroup and stakeholder consensus-building, 15 HAPC pharmacist EPAs were developed. Among the workgroup, all 15 EPAs reached ≥ 70% consensus, indicating appropriate internal validity. In a national survey of 185 HAPC pharmacists with a 20% response rate, 13 EPAs were rated by most respondents as "essential" and 2 were rated by most respondents as "important but not essential." Respondents indicated the 15 EPA set represented the core professional activities of HAPC pharmacists well (median rating of 5 on a Likert-like scale, IQR 1). CONCLUSION: Fifteen consensus EPAs describe essential activities of HAPC pharmacists in direct patient care, leadership, education, and scholarship. These EPAs will further guide pharmacist training programs, HAPC services seeking to incorporate a specialized pharmacist on the team, and currently practicing HAPC pharmacists.

A Case Report of Phenobarbital for Proportionate Sedation to Control Refractory Symptoms at the End of Life in an Opioid Tolerant Patient.

End of life (EoL) and refractory symptom management is a growing clinical topic and there is minimal literature to support effective treatment strategies, especially in individuals with a substance use disorder or opioids and/or benzodiazepine tolerance. We report the successful use of phenobarbital for proportionate EoL sedation in a 57-year-old man with opioid use disorder (heroin) and metastatic urothelial carcinoma presenting to an acute care hospital with intractable back pain related to bone metastases. During his hospitalization, his daily opioid requirement exceeded 1 gram of morphine equivalent daily dose (MEDD) with suboptimal pain control. The patient's clinical course was complicated by active heroin withdrawal, psychosocial suffering, and disease progression. Despite use of high-dose opioids and benzodiazepines, pain and anxiety were poorly controlled. After an acute medical decompensation, a goals of care discussion was held with his family and a determination with informed consent was made to change patient status to do not attempt resuscitation and proportionate sedation with phenobarbital was initiated to target refractory pain and agitation. Phenobarbital was continued for approximately 15 hours before patient peacefully died. Findings from this case report demonstrate the successful use of phenobarbital in opioid use disorder and benzodiazepine tolerance with intractable pain.

Multicentered Evaluation of Palliative Care Pharmacists' Interventions and Outcomes in California.

Introduction: The palliative care (PC) pharmacist's role within PC teams is increasingly recognized with favorable outcomes being reported. Methods: Retrospective study evaluated hospitalized adults seen by PC pharmacists, as part of PC consultation team at three California institutions. The primary objective was to categorize pharmacists' interventions. Secondary end points included length from admission to PC pharmacist involvement and symptom improvement following pharmacist intervention. Results: Data were collected for a total of 557 patients. Over the study period, the PC pharmacists provided 1466 medication recommendations and 2545 nonsymptom-based interventions. Average length of stay (LOS) was 15.6 days with mean time to PC service referral of 3.6 days. PC pharmacist consult occurred after a mean of 4.3 days after PC team consulted. LOS was significantly lower if seen by PC pharmacist within 72 hours of PC consultation, 12.3 days versus 24.5 days (p < 0.001), as well as when serving as lead clinician 9.3 days versus 15.5 days (p < 0.001). Achievement of severity goal was significantly higher at 24 and 72 hours assessment periods when received a medication recommendation for pain, dyspnea, anxiety, and constipation. Conclusion: PC pharmacists provide substantial transdisciplinary interventions. Significantly decreased LOS was found when PC pharmacist was involved within 72 hours of initial PC consultation and when served as lead clinician. Improved symptom goal attainment was demonstrated for pain, dyspnea, anxiety, and constipation. In summary, integration of a PC pharmacist on a PC team can be relied upon to provide patient-centered, transdisciplinary care and enhance symptom management.

Clinical Tolerability and Safety of Tramadol in Hospitalized Patients.

Tramadol is a schedule IV, monoaminergic and µ-opioid-receptor analgesic with unique pharmacology properties. Though it is well established and widely utilized, there is little guidance on tramadol's place in therapy, including tolerability, safety and monitoring guidelines. Retrospective chart review of 250 patients who received oral tramadol during their hospitalization from January 1, 2018 to December 31, 2018. Of the 250 patients, 10.8% had cancer as their primary diagnosis while 8.8% were admitted for hematologic reasons. 79.1% of patients had acute pain. Palliative care consult or ICU admission resulted in significant discontinuation of tramadol (p < 0.05 odds ratio 6.88, 2.39). There was no significant relationship of hypoglycemia when evaluating days on tramadol, total number of doses on tramadol, and MEDD start and end (p = 0.36, 0.88, 0.15, 0.23 consecutively). The longer that patients were on tramadol and the more doses they received during their inpatient stay, the greater risk of a severe drug-drug interaction (p < 0.05; R 0.29). In hospitalized patients, the risk of major and severe drug-drug interactions with tramadol increased with dose and duration. Hospital medicine, bone marrow transplant, and emergency medicine teams predominantly used tramadol.

The effect of sleep quality, sleep components, and environmental sleep factors on core curriculum exam scores among pharmacy students.

INTRODUCTION: Sleep deprivation is associated with poor academic performance, although the impact on pharmacy students has been minimally reported. This study examined sleep quality in pharmacy students in the first (P1), second (P2), and third (P3) professional years during perceived low and high stress periods in a course. Individual sleep and environmental factors were also explored. METHODS: This prospective cohort study used an 18-item survey adapted from the Pittsburgh Sleep Quality Index (PSQI) that included demographics, individual sleep components, and factors affecting sleep. Surveys were administered at the beginning of the quarter (low stress) and the week before final exams (high stress). Chi-square tests compared categorical variables; ANOVA/ANCOVA tests compared continuous variables. RESULTS: During high stress, PSQI scores worsened among all classes and was significant for the P3s. Average sleep duration was 6.64 (SD 1.18) and 6.8 (SD 1.18) hours per night for P1s and P3s, respectively, at the beginning of the quarter; both groups had significant reduction in sleep duration at the end of the quarter. There were no significant correlations between PSQI and exam scores. Factors impacting sleep such as exercise, use of technology at bedtime, and work hours outside of school decreased during high times of stress, for P1s, P2s, and P3, respectively. CONCLUSIONS: Students demonstrated worsening sleep quality during high stress periods and less sleep than recommended. Academic performance was not adversely affected. Future research should use sleep logs and other performance measures to determine the impact of sleep quality on academic success and wellbeing.

A Multi-Centered Case Series Highlighting the Clinical Use and Dosing of Lidocaine and Mexiletine for Refractory Cancer Pain.

Lidocaine infusion for pain control has been used for years. While some centers transition from continuous infusion lidocaine to oral mexiletine, there are no published studies to guide this conversion in pain and palliative care settings. This is a retrospective case series of 10 cancer patients across four institutions, with attention to dosing of both agents, and subsequent decrease in morphine-equivalent daily dosing (MEDD). The mean age was 55 years (range 34-78). The mean bolus dose of lidocaine was 1.6 mg/kg, infused over an average of 24 minutes, followed by a mean continuous infusion rate of 1.1 mg/kg/hr, and the infusion was continued for an average of 14.1 hours (range of 0.2 - 28 hours). The mean starting daily mexiletine dose was 400 mg (in 2-3 divided doses) and final dosing averaged 500 mg/day. The mean MEDD prior to starting lidocaine was 1118 mg/24 hours, which, by the time of final mexiletine dosing, was 882 mg/24 hours, a 21% MEDD reduction. The average hospital length of stay was 14 days. There was no lidocaine-induced toxicity and no lidocaine levels were obtained. Two of the 10 patients stopped mexiletine early, one from confusion four days after initiation of mexiletine, and the other after six weeks due to dizziness and visual changes. For cancer patients with suboptimal pain control on large doses of opioid, lidocaine infusion followed by oral mexiletine was well tolerated and effective.

Characteristics of Hospitalized Patients Screening Positive for Delirium.

BACKGROUND: Delirium in the hospitals leads to worse outcomes for patients. There were no previous studies that characterize patients with delirium from multiple hospital locations. OBJECTIVE: To describe patient characteristics screening positive for delirium and identify any correlations with hospital location and medication use. DESIGN, SETTINGS, PATIENTS: Retrospective chart review of 227 hospitalized patients from a large, academic, tertiary referral, 2-campus health system. Patients were ≥18 years old and had delirium for at least ≥24 hours. Validated delirium screening tools were utilized. MEASUREMENTS: Patients' demographics, inpatient stay information, delirium episodes characteristics, drugs, and palliative and psychiatry teams' involvement. RESULTS: Most patients were older with a mean age of 64.1 years. The most common primary diagnoses were infection, cardiac, and pulmonary. Average length of delirium was 7.2 days (standard deviation [SD] = 8.2), and average length of stay (LOS) was 18.7 days (median = 10.5, SD = 35.1, 95% confidence interval = 14.1-23). Thirty-day readmission rate was 24.8% (65/262 hospitalizations); 12.8% of patients died in the hospital (29/227). Around one-third of hospitalizations had involvement of palliative care, palliative psychiatry, or general psychiatry team. There was a decrease in the number of medications administered 24 hours after the first recording of delirium compared to the immediate preceding 48 hours. Those hospitalizations where delirium first occurred in the intensive care unit (ICU) did have a longer LOS (average = 22.9, SD = 45.7) than those where delirium first occurred outside the ICU (average = 14.8, SD = 20.5). Patients were likely to have received an opioid within 48 hours in 51% of hospitalizations and to have received benzodiazepines in 16% of hospitalizations. CONCLUSION: In our study, we found that delirium significantly impacted length of delirium episode, number of episodes of delirium, length of hospital admission, and mortality. The population most sensitive to the impacts of delirium were elderly patients.

Emerging Challenges to the Safe and Effective Use of Methadone for Cancer-Related Pain in Paediatric and Adult Patient Populations.

Methadone continues to be an important medication for the treatment of paediatric and adult cancer-related pain. Appropriate patient selection to ensure safe and effective treatment by a team of clinicians who appreciate and are familiar with methadone and its unique pharmacology is crucial. Unlike morphine and other more common opioids, methadone is purported to have involvement with delta-opioid receptor and higher affinity as an N-methyl-D-aspartate-receptor antagonist. Clinically this gives it the advantage of being effective for both nociceptive and neuropathic pain, but also may be useful in the setting of tolerance to other opioids. Methadone also comes in multiple available formulations that can be administrated through a variety of routes beyond the oral route. Challenges with methadone in treating cancer-related pain include drug interactions specifically as it relates to new targeted cancer therapies. Recent guidelines recommend electrocardiogram monitoring with methadone and there is potential for additive cardiac toxicity in the oncology setting. Appropriate dosing of methadone for pain management given age, organ dysfunction, and patients who are on methadone maintenance therapy are also key factors. This article aims to provide clinicians with evidence and clinical practice guidelines for safe and appropriate use of methadone including indication, initiation, and monitoring given its complexity for management of pain in the dynamic oncology setting.

Proton-pump inhibitor use is associated with a broad spectrum of neurological adverse events including impaired hearing, vision, and memory.

Proton-pump inhibitors, PPIs, are considered effective therapy for stomach acid suppression due to their irreversible inhibition of the hydrogen/potassium pump in the gastric parietal cells. They are widely prescribed and are considered safe for over-the-counter use. Recent studies have shown an association between PPI use and Alzheimer dementia, while others have disputed that connection. We analyzed over ten million United States Food and Drug Administration Adverse Event Reporting System reports, including over forty thousand reports containing PPIs, and provided evidence of increased propensity for memory impairment among PPI reports when compared to histamine-2 receptor antagonist control group. Furthermore, we found significant associations of PPI use with a wide range of neurological adverse reactions including, migraine, several peripheral neuropathies, and visual and auditory neurosensory abnormalities.