Kyle P. Edmonds

Clinical utility of naloxegol in the treatment of opioid-induced constipation

Opioids are a class of medications frequently used for the treatment of acute and chronic pain, exerting their desired effects at central opioid receptors. Agonism at peripherally located opioid receptors, however, leads to opioid-induced constipation (OIC), one of the most frequent and debilitating side effects of prolonged opioid use. Insufficient relief of OIC with lifestyle modification and traditional laxative treatments may lead to decreased compliance with opioid regimens and undertreated pain. Peripherally acting mu-opioid receptor antagonists (PAMORAs) offer the reversal of OIC without loss of central pain relief. Until recently, PAMORAs were restricted to subcutaneous route or to narrow patient populations. Naloxegol is the first orally dosed PAMORA indicated for the treatment of OIC in noncancer patients. Studies have suggested its efficacy in patients failing traditional constipation treatments; however, insufficient evidence exists to establish its role in primary prevention of OIC at this time.

Risk of respiratory depression with opioids and concomitant gabapentinoids

Introduction The combination of opioids and central nervous system depressants such as benzodiazepines and barbiturates has an additive effect on the frequency of oversedation and respiratory depression requiring naloxone use in hospitalized patients. Gabapentinoids (gabapentin and pregabalin) are frequently prescribed with opioids for their opioid-sparing and adjuvant analgesic effects. There is limited literature on the risk of respiratory depression due to the combination of opioids and gabapentinoids requiring naloxone administration. Methods This retrospective study evaluated patients who were prescribed opioids and at least one dose of naloxone between March 1, 2014 and September 30, 2016. The primary objective of this study was to compare the frequency of respiratory depression among patients who received naloxone and opioids (non-gabapentinoid group) with those who received naloxone, opioids, and gabapentinoids (gabapentinoid group). Secondary objectives included comparing the association of oversedation, using the Pasero Opioid-induced Sedation Scale, and various risk factors with those in the gabapentinoid group. Results A total of 153 patient episodes of naloxone administration (102 in the non-gabapentinoid and 51 in the gabapentinoid groups) in 125 unique patients were included in the study. For the primary objective, there were 33 episodes of respiratory depression associated with the non-gabapentinoid group (33/102=32.4%) versus 17 episodes of respiratory depression with the gabapentinoid group (17/51=33.3%) (p=0.128). Secondary objectives showed a significant association between respiratory depression and surgery in the previous 24 hours (p=0.036) as well as respiratory depression and age >65 years (p=0.031) for patients in the non-gabapentinoid group compared to the gabapentinoid group. Conclusion There was no significant association of respiratory depression in the gabapentinoid group versus the non-gabapentinoid group. There was an increased risk of respiratory depression in the gabapentinoid group, specifically in patients who had surgery within the previous 24 hours.

Hydromorphone-induced chorea as an atypical presentation of opioid neurotoxicity: A case report and review of the literature:

Background: While opioid-induced myoclonus is well described, there are limited reports of opioid-induced chorea. Here we present the first case of chorea as a manifestation of opioid neurotoxicity due to hydromorphone. Case presentation: A 20-year-old woman presenting with fevers and cutaneous lesions was diagnosed with hemophagocytic lymphohistiocytosis secondary to primary cutaneous lymphoma. Surgical resection of a cutaneous lesion was complicated by severe postoperative pain requiring rapid opioid dose escalation. Seven days after hydromorphone was initiated, she developed positive myoclonus, hallucinations, delirium, and involuntary, flowing movements consistent with chorea. She had no personal or family history of nervous system disorders and was not taking any medications associated with drug-induced chorea. Case management: The remainder of her neurologic examination was unremarkable. Her renal function was normal and no etiology was found on neuroimaging or laboratory workup. Hydromorphone was discontinued and pain control was achieved with fentanyl. Case outcome: The patient’s neurotoxic symptoms including chorea resolved within 72 h of hydromorphone discontinuation. Conclusion: Further studies are needed to determine which patients have a unique sensitivity to opioids predisposing them to chorea. Clinicians should be aware that chorea may be a sign of such toxicity so that rapid corrective action can be taken.

Identifying Patterns of Delirium in Hospitalized Patients on Dexamethasone Using a Chart Abstraction Tool

Abstract Delirium is a neuropsychiatric syndrome that can occur in hospitalized patients, including in palliative care settings. The aim of this study is to describe patterns of delirium in patients receiving dexamethasone at the request of an inpatient palliative consultation team by using a modified chart abstraction tool. This retrospective study analyzed patterns of delirium development in adult hospitalized patients receiving opioids for cancer-related pain and initiated on dexamethasone with recommendation from the palliative care team. Primary end point described patterns of delirium, and the study secondarily analyzed source delirium documentation, Glasgow Coma Scale score, Richmond Agitation-Sedation Scale score, and Eastern Cooperative Oncology Group Performance pre- and post-dexamethasone administration. A total 59 patients were included in this retrospective chart review. There was no difference in delirium rate during the pre- and post-dexamethasone periods (n = 35 and 31, respectively; P = .62). There also were no significant differences in mental status, agitation, or functional status before or after dexamethasone, although data were limited by electronic health record incompleteness. Evidence of delirium was most commonly documented in physician notes (n = 58, 71%). The findings showed that incidence and severity of delirium were not impacted after patients were started on dexamethasone as recommended by an inpatient palliative team, although data were limited.

Prescribing Trends of Palliative Care Team's Use of Dexamethasone for Cancer-Related Pain

ABSTRACT Opioids are first-line therapy for cancer-related pain. In addition, corticosteroids are commonly utilized as adjuvant analgesics for pain and other symptoms in the oncology setting with limited supporting data. A retrospective analysis was conducted evaluating adult hospitalized patients receiving opioids who received once-daily dexamethasone on the recommendation of a specialty palliative care team during their hospitalization from January 1, 2015, to January 1, 2016. Primary end point was to describe prescribing patterns of dexamethasone in this patient population and secondarily examining any effect on oral morphine equivalent daily dose (MEDD), numeric pain score (NPS), and unwanted effects at 24 and 48 hours after the first dose of dexamethasone. Fifty-nine patients received an average dose of 13 mg (SD = 10) of dexamethasone for cancer-related pain, primarily acute pain (n = 36, 61%). Many died before hospital discharge or soon thereafter (n = 28, 47.5%). Although not statistically significant, our study shows a decrease of 23% and 19% in MEDD and NPS, respectively, without change in WBC after dexamethasone. A specialty palliative care team most often used once-daily dexamethasone for cancer-related pain in patients near the end of life. There were trends toward lower MEDD and NPS, but more robust studies are needed for validation.

Case Report: Utility of Ketamine, Lidocaine, and Mexiletine as Nonopioid Adjuvants in Complex Cancer-Associated Pain

ABSTRACT Ketamine, lidocaine, and mexiletine are potential nonopioid adjuvant medications for the use of refractory cancer-related pain, particularly when opioids are demonstrating limited objective benefit. This is a case report of a single patient admitted to a large academic medical center in the United States. The patient is a 43-year-old woman with a history of Crohns disease complicated by rectal squamous cell carcinoma and complex, progressive, and intractable pelvic and rectal pain. Over the course of hospitalization, her pain demonstrated limited opioid responsiveness despite marked fluctuations of her oral morphine equivalent doses. She also demonstrates variable responsiveness to ketamine. Lidocaine continuous infusion ultimately proves beneficial, and she is discharged after conversion to oral mexiletine. An overview of the hospital systems protocols for ketamine and lidocaine continuous infusions for pain and considerations for transitioning to mexiletine from lidocaine infusion are included.

Multicentered Study Evaluating Pharmacy Students’ Perception of Palliative Care and Clinical Reasoning Using Script Concordance Testing

Introduction: As the role of the pharmacist on the transdisciplinary palliative care team grows, the need for adequate instruction on palliative care and clinical reasoning skills in schools of pharmacy grows accordingly. Methods: This study evaluates second- and third-year pharmacy students from 6 accredited schools of pharmacy that participated in surveys before and after the delivery of a didactic palliative care elective. The survey collected student demographics, perceptions of the importance of and student skill level in palliative care topics. The script concordance test (SCT) was used to assess clinical decision-making skills on patient cases. Student scores on the SCT were compared to those of a reference panel of experts. Results: A total of 89 students completed the pre-/postsurveys and were included in data analysis. There was no statistically significant difference in student perceived importance of palliative care skills before and after the elective. Students from all 6 institutions showed significant increase in confidence in their palliative care skills at the end of the course. There was also a significant improvement across all institutions in clinical reasoning skills in most of the SCT questions used to assess these skills. Conclusions: Students choosing an elective in palliative care likely do so because they already have an understanding of the importance of these topics in their future practice settings. Delivery of a palliative care elective in the pharmacy curriculum significantly increases both student confidence in their palliative care skills and their clinical reasoning skills in these areas.