Non-pain Symptomatic Management in Palliative Care OLIVER A. CERQUEIRA, D.O. ASSISTANT PROFESSOR OF INTERNAL MEDICINE CLERKSHIP DIRECTOR, INTERNAL MEDICINE OU-TULSA SCHOOL OF COMMUNITY MEDICINE Objectives Apply generalized principles of symptom management to "real world" clinical scenarios Choose appropriate management for a variety of non-pain symptoms that are addressed by palliative care Palliative Care So, what S/Sx are out there to be addressed? Nausea & Vomiting** Dyspnea** Constipation Diarrhea Ascites/Pleural Effusions Bowel Obstruction Fatigue Singultus Depression Lymphedema/Edema Anuria Insomnia Hot Flashes Anxiety Delirium/Confusion** Secretions Pruritus Fever Cough Anorexia/Cachexia Xerostomia Mucositis/Stomatitis Pressure Ulcers/Wound Care/Wound Odor Bladder Spasms Candidiasis Generally, what are two ways to manage S/Sx? Non-pharmacologic/Mechanical Pharmacologic Routes of Administration PO IV IM Sub-Q Buccal & SL TD PR Intranasal/Inhalation Principles of Symptom Control Four domains of the human suffering experience: Physical Emotional Social Spiritual Principles of Symptom Control Do NOT overlook symptomatic management while focusing on disease-oriented care e.g. Pleuritic CP & PNA When possible, identify the underlying pathophysiology &/or mechanism Symptoms are the patient’s experience of the illness The clinician is obligated to relieve those symptoms Unrelieved suffering is demoralizing & demeaning Suffering patients may lose the will to live, become depressed & withdrawn, & decline more rapidly Principles of Symptom Control Treatment considerations: Anticipate predictable complications of disease states Anticipate associated complications of palliative treatments e.g. poor home support & complex treatment regimens; low income & medication affordability Ultimately, patient’s goals of care drive symptomatic management decisions e.g. opioids & N/V, constipation, sedation, delirium Evaluate for psychosocial difficulties e.g. colorectal cancer patients & bowel obstruction; head & neck cancer patients & sudden exsanguination e.g. clarity of mind vs. suffering pain Frequent re-evaluation Nausea & Vomiting Occurs 60-70% of patients with advanced cancer Prevention is key: Regular dosing of antiemetics can often prevent recurrent nausea Associated with autonomic s/sx, including pallor, cold sweats, decreased respiratory rate, & sometimes diarrhea Hypersalivation Cardiac rhythm disturbances may occur Gastric emptying is reduced in the presence of nausea – don’t assume PO medications will work, even if there is no vomiting! Nausea & Vomiting – 4 Inputs Nausea & Vomiting Nausea & Vomiting – Pharmacologic Treatment V.O.M.I.T. acronym Vestibular Cholinergic, Histaminic Scopolamine, Promethazine Obstruction of bowel by constipation (NOT mechanical obstruction) Cholinergic, histaminic, likely 5HT3 Stimulate myenteric plexus – Senna DysMotility of the upper gut Cholinergic, histaminic, 5HT3, 5HT4 Metoclopramide Infection, Inflammation Cholinergic, histaminic, 5HT3, NK1 Toxins stimulating CTZ Dopamine 2, 5HT3 Haloperidol, Odansetron, Prochlorperazine Nausea & Vomiting – Pharmacologic Treatment Nausea & Vomiting – Non-pharmacologic Ginger Root 5HT3 antagonism in animal models Measures to enhance gastric emptying and decrease gastric distention Liquid diet Frequent small meals Foods low in fats & fiber, high in protein Measures to minimize other noxious or associated stimuli Cool foods Foods with a pleasant appearance & w/o odors Acupuncture At the P6 or pericardium 6 point Produces vagal modulation & enhances 5HT3RA efficacy Cognitive—Behavioral Therapy Induces muscle relaxation & reverses autonomic arousal that accompanies ALL nausea Delirium - Definition Delirium – Subtype Manifestations Three subtypes based on arousal levels & psychomotor behavior Hyperactive delirium Hallucinations, agitation, delusions, & disorientation Hypoactive delirium Decreased consciousness, somnolence In PC, is more common – up to 80% Mixed-form with alternating features Delirium - Pathophysiology Delirium – Risk Factors & Causes Delirium – Risk Factors & Causes Medications are the most common identifiable causes of delirium in the hospital setting! Anti-cholinergics Sedative-hypnotics Opioids Other common causes: Metabolic derangements Infections CNS pathology Drug/alcohol withdrawal Delirium – Risk Factors & Causes Delirium – Pharmacologic Treatment Benzodiazepines may cause paradoxical worsening of symptoms (possibly by a serotonergic mechanism) & should not be used first line Use lowest doses possible, especially with haloperidol as EPS side effects are dosedependant! IV haloperidol may cause less EPS than PO When reaching maximum dosages of haloperidol, one option is to add or switch to a more sedative neuroleptic Delirium – Non-pharmacologic Dyspnea Experienced by up to 70% of terminally ill cancer patients at some point during the course of their disease Diminishes functional status, social activities, QOL, & the will to live In one multi-center study from 2000, terminal sedation was prompted by dyspnea 3X more commonly than by pain The typical pattern is one of chronic dyspnea, punctuated by unpredictable, but expected, acute episodes SUBJECTIVE!! e.g. patients may be hypoxic & “look dyspneic,” but when well-palliated, they report no sense of dyspnea Patient self-report is the only accurate measure of dyspnea Dyspnea – Multidimensional Dyspnea – Physiology & Pathophysiology The sensory cortex receives copies of respiratory motor commands arising from the medulla or motor cortex & sensory information from peripheral chemoreceptors & mechanoreceptors Dyspnea occurs if the degree of motor output required is perceived to be unsustainable or disproportionate to the sensory information received Dyspnea – Generalized Treatment Measures Address the underlying etiology or etiologies, if at all possible Reduce the need for exertion Repositioning, usually to a more upright position Keep the compromised lung down in unilateral pulmonary disease Improve air circulation – open doors & windows, use a fan Avoid strong odors, fumes, & smoke Identify & avoid any triggers that precipitate or worsen dyspnea Dyspnea – Opioids First-line therapy Can be used alone or aside reversible etiologies Most beneficial for dyspnea at rest Evidence has repeatedly shown that opioids can be safe & effective at controlling dyspnea in several clinical populations, including COPD, CHF, pulmonary fibrosis, & cancer Respiratory depression is uncommon when titration is appropriate & is almost always preceded by drowsiness/sedation Hold Parameters Dyspnea – Opioids Reversal agents (i.e., naloxone) should only be used in the setting of life-threatening opioid toxicity Most published trials studied morphine, but trials of other opioids such as fentanyl, M6G, & hydromorphone suggest a class effect Most common adverse effects experienced in this population: Constipation, nausea, sedation Dyspnea – Opioids Mechanisms by Which Opioids May Reduce Dyspnea: Decreased metabolic rate and ventilatory requirements Reduced medullary sensitivity & response to hypercarbia or hypoxia Alteration of neurotransmission within medullary respiratory center Cortical sedation (i.e., suppression of respiratory awareness) Analgesia reduction of pain-induced respiratory drive Vasodilation (i.e., improved cardiac function) Anxiolytic effects Dyspnea – Opioids Opiate-naïve older age or patients with CKD Consider reducing starting dose by ½ Avoid morphine in renal disease if possible DOE or dyspnea with movement Give 30 minutes prior to activity If on stable IR dosage, consider trial of LA as baseline with IR PRN in between doses Dyspnea – Other Treatment Benzodiazepines Addresses concomitant anxiety No evidence that there is a direct benefit Oxygen Often patients report improved dyspnea, even when not hypoxemic or when they remain hypoxemic ? Placebo effect due to inherent medical symbolism Some studies have demonstrated dampening of dyspnea due to stimulation of the trigeminal nerve, V2 branch Depending on patient preference, generally avoid face masks Dyspnea – Pursed Lip Breathing The End!! References Bruera, Eduardo et al. Textbook of Palliative Medicine. 1st ed. Houston, TX: CRC Press; 2009. Adamis, D. et al. Delirium Scales: A review of current Evidence. Aging & Mental Health. 2010; Vol 14, No.5;543-555. Walsh, Declan et al. Palliative Medicine. 1st ed. Philadelphia, PA: Saunders; 2008. Karnani, NG. Management of Selected Non-Pain Symptoms at the End of Life. Northeast Florida Medicine. 2010; Vol 61, No.4:18-21. Rousseau, Paul. Nonpain Symptom Management in the Dying Patient. Hospital Physician. 2002; Feb:51-56. Montagnini, Marcos et al. Non-Pain Symptom Management in Palliative Care. Clinics in Family Practice. 2004;Vol 6, No.2:395422. Quill, Timothy E. et al. Primer of Palliative Care. 5th ed. Glenview, IL: American Academy of Hospice and Palliative Medicine; 2010. Weissman, DE. Dyspnea at End-of-Life, 2nd ed. Fast Facts and Concepts. July 2005;27. http://www.eperc.mcw.edu/fastfact/ff_027.htm. Accessed Feb 10, 2013. Weissman, DE. Diagnosis and Management of Terminal Delirium, 2nd ed. Fast Facts and Concepts. July 2005;1. http://www.eperc.mcw.edu/fastfact/ff_001.htm. Accessed Feb 10, 2013. Quijada, E, Billings JA. Pharmacologic Management of Delirium; Update on Newer Agents, 2nd Ed. Fast Facts and Concepts. July 2006;60. http://www.eperc.mcw.edu/fastfact/ff_060.htm. Accessed Feb 10, 2013. Hallenbeck J. The Causes of Nause and Vomiting (V.O.M.I.T.), 2nd Ed. Fast Facts and Concepts. July 2005; 5. http://www.eperc.mcw.edu/fastfact/ff_005.htm. Accessed Feb 10, 2013. Shirk, Mary B. et al. Unlabeled Uses of Nebulized Medications. Am J Health-Syst Pharm. Sept 15, 2006; Vol 63: 1704-1716. Kallet, Richard H. The Role of Inhaled Opiods and Furosemide for the Treatment of Dyspnea. 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