Prommer, Eric

61 Background: Patients with cancer often have complex symptoms and morbidity that prompt frequent Emergency Department visits. The length of stay in the ED for cancer patients exceeds that of patients without cancer. Patients with cancer are also more likely to be admitted, but are often discharged within 72h. Protracted ED visits, extensive investigations, and the burdens of even a short admission may be distressing and may not be aligned with patients’ care goals and preferences. Furthermore, the healthcare resources dedicated to these patients is considerable and has economic implications. We recently established a Supportive Care Infusion Center (SCIC), an on-campus outpatient unit where patients can receive treatments for symptom relief and comfort; they are assured integrated palliative care with routine oncologic care. We believe there is a subset of cancer patients who can be safely transferred from the ED to the SCIC for appropriate care. Methods: We are retrospectively evaluating cancer patients admitted through the ED to validate clinical parameters likely to lead to admission, and also identify any differences between patients admitted for <72h vs >72h. Patients are analyzed based on symptoms, cancer type, prior cancer therapies, performance status, comorbidities, and presence/absence of advance care planning as well as previous contact with Palliative Care. Data are also being gathered on patient outcomes, including mortality within 60d of admission. Results: Previously established indicators predictive of admission included shortness of breath and SIRS criteria, which our current review validates. We also observe that patients admitted for >72h have greater symptom burden and comorbidities and have received multiple lines of therapy. They also less frequently have advance care planning in place. Data analysis is ongoing. Conclusions: There exists a difference between cancer patients admitted >72h and those discharged within 72h. Awareness of these characteristics may lead to improved workflow in the ED. Identifying patients who may be suitable for transfer to an outpatient supportive care unit rather than short-term admission will also facilitate cost-effectiveness. Future direction includes evaluation of outcomes such as mortality, quality of life, and patient-caregiver satisfaction.

Opioid-related bowel dysfunction is a common and potentially severe adverse effect from treatment with opioid analgesics. Its development is not dose related, nor do patients develop tolerance. Opioid-induced constipation (OIC) can lead to fecal impaction, bowel obstruction, and bowel perforation as well as noncompliance with opioid analgesics and poor quality of life. Routine administration of laxatives is necessary to maintain bowel function, and, in refractory cases, other modalities must be pursued. Available options are limited but include peripherally acting μ-opioid receptor antagonists (PAMORAs), including methylnaltrexone. Naloxegol is a newly developed PAMORA that is available through the oral route. At the therapeutic dose of 25 mg daily, naloxegol is effective and safe, with a limited side effect profile and is associated with preservation of centrally mediated analgesia. In this article, we discuss the pharmacokinetics, pharmacodynamics, adverse effects, clinical trials, and cost considerations of naloxegol. Finally, we discuss its potential role as a novel key treatment for OIC in palliative medicine patients.

Buprenorphine (BUP) is a semisynthetic derivative of the opium alkaloid thebaine found in the poppy Papaver somniferum. Its chemical structure contains the morphine structure but differs by having a cyclopropylmethyl group. Buprenorphine is a potent µ opioid agonist. Buprenorphine undergoes extensive first-pass metabolism in the liver and gut. The development of a transdermal BUP formulation in 2001 led to its evaluation in cancer pain. This article provides the practitioner with an update on the current role of BUP in cancer care. It highlights data suggesting effectiveness in various types of cancer pain. The article reviews pharmacology, routes of administration, adverse effects, drug interactions, and cost considerations.

Bone metastases cause devastating clinical complications leading patients to have pain, poor quality of life, loss of mobility, and autonomy. Complications from osseous metastases cause a big economic burden reflected by repeated admissions for uncontrolled symptoms. Management of symptoms associated with bone metastasis includes systemic analgesics, glucocorticoids, radiation (external beam radiation and radiopharmaceuticals), ablative techniques (radiofrequency ablation and cryoablation), chemotherapeutic agents, hormonal therapies, interventional techniques (eg, kyphoplasty), and surgical approaches. Bisphosphonates have become a standard therapy for bony metastasis. They bind to bone eventually inhibiting osteoclast action. Bisphosphonates decrease fractures when given routinely. Adverse effects of bisphosphonates include osteonecrosis of the jaw and renal insufficiency. Late last year, the Food and Drug Administration approved denosumab to prevent skeletal-related events (SREs) associated with metastatic solid tumors. This drug is a monoclonal antibody that inhibits the receptor activator of nuclear factor κB (RANK)–RANK ligand interaction. Clinical trials have shown superiority over bisphosphonates for the prevention of SREs. This article reviews the mechanism of action, pharmacology, adverse effects, and clinical trial evidence for this new drug.

Levorphanol (levo-3-hydroxy- N-methylmorphinan) is a step 3 opioid first developed in the 1940s as an alternative to morphine. Levorphanol belongs to the morphinan opioid series. Levorphanol has greater potency than morphine and is a potent N-methyl-D aspartate (NMDA) antagonist. Levorphanol interferes with the uptake of norepinephrine and serotonin, which makes it potentially useful for neuropathic pain. Glucuronidation changes Levorphanol to Levorphanol-3-glucuronide with excretion by the kidney. Levorphanol has a long half-life and may accumulate with repeated dosing. Levorphanol can be administered orally, intravenously, and subcutaneously. This article provides an update regarding the pharmacodynamics, pharmacology, and clinical efficacy of this often overlooked step 3 opioid.

Anticholinergics, or antimuscarinic drugs, are drugs that competitively inhibit the action of acetylcholine at muscarinic receptors, leading to a blockade of the actions of the parasympathetic nervous system at sites where overactivity can lead to increased symptom burden. Successful blockade of the parasympathetic nervous system ultimately leads to decreased production of secretions in the salivary, bronchial, and gastrointestinal tracts. These effects are often used for several symptoms that originate due to parasympathetic nervous system overactivity, such as the “death rattle” and malignant bowel obstruction. Anticholinergic agents are divided into either tertiary amines or quaternary ammonium compounds, which differ in their ability to cross into the central nervous system. Quaternary compounds do not cross into the central nervous system and have a different adverse effect profile than the tertiary amines. The purpose of this review is to highlight anticholinergic agents, their pharmacology, and an evidence-based assessment of their role in palliative care.

Olanzapine is an atypical antipsychotic agent of the thienobenzodiazepine class. Olanzapine blocks multiple neurotransmitter receptors, including dopaminergic (D 1 , D 2 , D 3 , and D 4 ), serotonergic (5-hydroxytryptamine 2A [5-HT 2A ], 5-HT 2C , 5-HT 3 , and 5-HT 6 ), adrenergic (α 1 ), histaminic (H 1 ), and muscarinic (M 1 , M 2 , M 3 , and M 4 ) receptors. Olanzapine has a high affinity for the 5HT 2A receptor, which is up to 5 times greater than the dopamine receptor, resulting in less propensity to the development of extrapyramidal side effects. The affinity of olanzapine for multiple receptors has lead to the identification of olanzapine as an important agent in the treatment of delirium, nausea, and vomiting. Olanzapine has been demonstrated to have opioid-sparing properties. Olanzapine is principally metabolized by glucuronidation, with a smaller metabolic contribution from the cytochrome oxidase system. Adverse effects of olanzapine include somnolence, postural hypotension, constipation, dizziness, restlessness, and weight gain. The purpose of this article is to outline the pharmacodynamics, pharmacology, and evidence for the use of olanzapine in palliative care.