Palliative Care of Respiratory Symptoms

Palliative Care of Respiratory Symptoms
James S. Botts, MD, FACP Southwest Area Medical Director VistaCare

Outline of Topics… Identification of the Patient with Endstage Pulmonary Disease Dyspnea Cough Pulmonary Infections Hemoptysis Pulmonary Hypertension and Cor pulmonale Primary Pulmonary Hypertension Pulmonary Fibrosis Pulmonary Emboli Stridor Neuromuscular Disorders & Restrictive Pulmonary Disease Bronchiectasis and Cystic Fibrosis α-1 Antitrypsin Deficiency List of Links Slide two is the outline of the presentation. As noted in the first column, I will begin with a brief description of the vagaries of identifying the patient who has end stage respiratory disease and a prognosis of less than six months. Next in the first column are listed the symptoms we will be covering which are found in many patients with end stage respiratory disease. The second column is a listing of several pulmonary disorders that deserve special mention in terms of palliative care.

Identification of Endstage Pulmonary Disease
No single event or parameter signals end stage Persistent dyspnea despite optimal medical treatment Dyspnea impairing efforts to leave home Increasing number of hospital admissions Limited improvement after hospitalization Increasing number of physician visits Onset of fear, anxiety or panic attacks Expression of concerns about dying No reference to oxygen saturation or other parameter of pulmonary function It is difficult to accurately identify those with a prognosis of six months or less Slide three attempts to identify factors associated with end stage pulmonary disease and a prognosis of less than six months. As you can see there is no single clinical event or laboratory study that can be held as a reliable indicator of a prognosis of less than six months. In particular, oxygen saturations and pulmonary function studies cannot be used as a lone indication of the six months or less prognosis. 1. Derek, D. et al. (2004). Oxford Textbook of Palliative Medicine, pp. 903

Identification of Endstage Pulmonary Disease
Using CMS LCD pulmonary guidelines 50% of patients qualifying for pulmonary disease will live six months or less (n = 94)* Pulse rate > 100 has the best correlation with a prognosis of six months or less in patients with endstage pulmonary disease 65.38% of patients meeting the CMS LCD guidelines for pulmonary disease with a pulse rate > 100 will live less than six months (n = 29)* * Hospice Eligibility Evaluation Database (HEED) ; J.S. Botts

Palliative Care of Dyspnea
Welcome every one to October’s First Friday phone call. For those that don’t know me I am Jim Botts, the Southwest Area Medical Director. Today we are to cover Palliative Care of Respiratory Symptoms. Main Menu…

Definition of Dyspnea (American Thoracic Society) “A subjective experience of breathing discomfort consisting of qualitatively distinct sensations that vary in intensity. Physiologic, psychologic and environmental factors all may play a role. The severity varies widely among patients.”(2) Slide 5 is the American Thoracic Society’s definition of dyspnea. As we all know, dyspnea is a subjective experience, however, the definition also includes reference to “qualitatively distinct sensations that very in intensity”. Assuming you are connected to the internet , double clicking the link at the bottom of the screen will take you to a full text consensus statement article on the mechanisms, assessment, and management of dyspnea by the American Thoracic Society. Throughout the remainder of the presentation, you will notice links at the bottom of some of the slides. Most will take you to the Pub MED site where an abstract of the article will appear. The links are all underlined. Those references not underlined will, of course, not link to anything. 2. American Journal of Respiratory and Critical Care Medicine - Jan 1999 ARS-1

Correlation of the complaint with the pathology of the underlying disease. Little correlation in general Some correlation of the following: “I am drowning.” – Pulmonary edema with CHF “I can’t get enough air in.” – Interstitial disease or pulmonary emboli.(2,3) “Tight”, “Constricted” – a sensation used by those with airways obstruction such as asthma and cystic fibrosis but not COPD Slide 6 describes the qualitative language patients use when describing their dyspnea. In reality, there are only a few descriptions that may sometimes identify the cause of the dyspnea. Note that the “tight”, “constricted” description is one that we all have heard from patients with angina as a source of their complaint. 2. Chest. 2005;127: 3. Excerpt: Chest. 2005;127:

The Language of Dyspnea
Other studies in the literature have attempted to judge whether or not there are diagnostic clues in the language patients choose to describe their dyspnea or the discomfort they associate with breathing. Mahler et al5 have explored the language that patients with seven different disease states (e.g., asthma, congestive heart failure, interstitial lung disease) use to describe their dyspnea. These authors presented their subjects with a list of 15 descriptors. The investigators then asked each patient to walk along a hospital corridor until he felt an intensity of dyspnea equal to a grade of 3, or moderate, on the Borg scale. Patients were then asked to select those descriptors that best characterized their discomfort after the walk. Of interest, only patients with diagnoses associated with airway obstruction (egg, asthma and cystic fibrosis but not COPD) chose terms that imply tightness, such as "tight" or "constricted," to describe their discomfort. Other terms, such as "work" or "inhalation" were not specific for any diagnostic category. This may make sense from the point of view of the pathophysiology in that asthma and cystic fibrosis, unlike any of the other diagnostic categories, are associated with edema, inflammation, and muscular constriction of the larger airways. The feeling of tightness may be a feeling generated by the stimulation of airway afferents, a physiologic event shared by, and specific to, these two disease entities. A criticism of the work of Mahler et al is, however, that their subjects were asked to choose their words from a list of descriptors that were given to them. In this author’s experience, when patients with asthma are asked to describe their dyspnea using their own words, very few will volunteer a descriptor similar to those given by Mahler et al. Invariably, however, the few patients who do volunteer the word "tight" will have asthma, and the few who volunteer "I can’t breathe in" will have interstitial lung disease or pulmonary emboli. It appears, then, that there is some link between the pathophysiology of a disease and the words that patients choose to describe their discomfort. The fact that very few subjects will use these words, however, should send us another message: that is, it is not reasonable to expect all people, even if they speak the same language, to link the same word or descriptor to a given sensation. Chest. 2005;127: << Back

Aorta and Carotid Arteries
Adapted From: Derek, D. et al. (2004). Oxford Textbook of Palliative Medicine, pp. 898 Motor Cortex Sensory Cortex Dyspnea Peripheral Chemoreceptors Aorta and Carotid Arteries Emotions Personality Central Chemoreceptors Medulla Corollary Discharge Sense levels of oxygen, carbon dioxide and pH of the blood. Midbrain Respiratory Center Sense levels of oxygen, carbon dioxide and pH of the blood. Slide 8 depicts the pathophysiology of dyspnea. As you can see, the Midbrain respiratory center receives input from chemoreceptors and mechanoreceptors and in turn sends messages to the sensory cortex and the respiratory muscles of breathing. The sensory cortex also receives messages resulting from emotions. The sensory cortex messages the motor cortex that then stimulates contraction of the muscles of breathing. The sensory cortex is also responsible for producing the sensation of dyspnea. Mechanoreceptors Lungs and Chest Wall Sense stretching of structures in lungs and chest wall Respiratory Muscles of Breathing Pathophysiology of Dyspnea

Palliative Care of Dyspnea Assessment of Dyspnea
Five etiologic categories Cardiac Pulmonary Neuromuscular Psychiatric / Social / Spiritual Any combination of the above Slide 9 lists the factors that may be responsible for the sensation of dyspnea. Of greatest importance is that dyspnea is often, just as pain is, multifactorial. Just treating the underlying system may not be enough to effect maximal relief.

History and Physical Examination Frequently identifies the specific system responsible for the dyspnea Indicated diagnostic testing follows Slide 10 emphasizes the importance of the history and physical examination which can frequently identify a specific system that is responsible for the dyspnea. Our hospice patients often will not want to have the usual diagnostic testing required to confirm the cause of the dyspnea, making the history and physical even more important in the diagnostic process.

Palliative Care of Dyspnea Assessment of Dyspnea - Testing
Pulmonary Testing ABG Chest X-ray Pulmonary Functions Bronchial Challenge High resolution CT Lung scan PET Diaphragmatic Fluoroscopy Cardiac Testing EKG Echocardiography Coronary angiography Myocardial perfusion scan Other Sleep studies Esophageal pH monitoring Laryngoscopy Slide 11 details some of the diagnostic tests that may be done to support the impressions of a good history and physical examination. As you can see, many of these tests are not practical to conduct on a terminal patient. Often old records can supply results of some of these tests. Often hospice and palliative care patients choose not to be tested, placing more reliance on the history and physical examination.

Reporting Intensity of Dyspnea Verbal numerical scales (0-10) VAS (Visual Analog Scale) Modified Borg Dyspnea Scale Slide 12 lists the common methods of assessing the severity of dyspnea. As you can see, the first two, the verbal numerical scale and VAS are similar to those used to assess pain. In the academic literature, the Modified Borg Dyspnea Scale seems to be used most frequently. Double clicking the link at the bottom of the screen will display the Modified Borg Dyspnea Scale. Link to Modified Borg Dyspnea Scale

Modified Borg Dyspnea Scale Intensity of Sensation Rating Nothing at all 0 Very, very, slight Very Slight Slight Moderate 3 Somewhat severe 4 Severe Very Severe Very, Very Severe 9 Maximal Derek, D. et al. (2004). Oxford Textbook of Palliative Medicine, pp. 899 << BACK

Common Physiological Measurements of Respiratory Disease Spirometry FEV1 is a POOR predictor of dyspnea and improvements in dyspnea after bronchodilators do not match improvements of FEV1(4,5) Oxygen saturation – with its limitations(6) NOT a good predictor of the subjective feeling of dyspnea Slide 15 reviews the common physiologic measurements that we do on pulmonary patients. The importance of this slide is to emphasize the fact that these physiologic measurements do not give us quantitative information about dyspnea. All patients with dyspnea do not have abnormal oxygen saturations. Likewise, all patients with oxygen saturations < 89% do not have resting dyspnea. 4. Derek, D. et al. (2004). Oxford Textbook of Palliative Medicine, pp. 899 5. Lareau, S.C. et al. (1999).Dyspnea in patients with chronic obstructive pulmonary disease: does dyspnea worsen longitudinally in the presence of declining lung function? Heart & Lung 6. eMedicine - Pulmonary Function Testing : Article by Raed A Dweik, MD, FACP, FCCP, FRCPC

Palliative Care of Dyspnea Treatment – Non-Pharmacologic
Influenza and pneumonia vaccines Cold facial stimulation (i.e. fan)(6) Nutrition(7) Weight gain for malnourished COPD (“pink puffer”) Weight reduction is accompanied by respiratory muscle weakness. Non-fluid weight gain will help correct this Weight gain is difficult to achieve – poor response to nutritional supplements Weight loss for hypercapnic COPD (“blue bloater”) Slide 16 addresses non-pharmacologic treatments for dyspnea. Prevention of influenza or pneumonia, of course, will relieve dyspnea associated with those illnesses. Facial cooling from a fan seems to help, and it is postulated that there are in fact signals that make it to the sensory cortex that help reduce the sensation of dyspnea. Weight reduction in the “pink puffer” can lead to weakening of the respiratory muscles. Attempts to make the pink puffer gain weight usually fail, though proper nutrition should be part of the care plan. Weight loss is a good thing for the blue bloater, reducing the tissue that has to be supplied with oxygen, and in turn reducing cardiopulmonary work. 6. Am Rev Respir Dis Jul;136(1):58-61 7. Am Rev Respir Dis Aug;142(2):283-8.

Controlled cough Deep breath followed by coughing For clearing secretions Forced expiration – incentive spirometry Good for prevention and treatment of atelectasis Follow with controlled cough to clear secretions Emotional, spiritual and social counselling These issues are important just as they are in the control of pain Addressing these factors may improve the sensation of dyspnea Slide 17 displays additional non-pharmacologic means of treating dyspnea. I suspect that most of those here today are like I am and tend to forget the importance of these non-pharmacologic measures. Again note that emotional, spiritual and social counselling can be of benefit to the patient with dyspnea just as they are with the treatment of pain. 8. Derek, D. et al. (2004). Oxford Textbook of Palliative Medicine, pp. 904

Exercise(8) Exercise is the best way to strengthen the respiratory muscles Methods Walking; stair climbing; Upper extremity and shoulder girdle strengthening These are accessory muscles of breathing Pulmonary rehabilitation Inspiratory resistance breathing No better than general reconditioning exercise alone in COPD patients Slide 18 describes the options for getting your patient to exercise and thus strengthen respiratory muscles. While many of our patients are home bound and not candidates for a formal pulmonary rehabilitation program, just the act of getting out of bed on a regular basis may help some patients with dyspnea. Inspiratory resistance breathing does not require the patient ambulating or leaving the home and I suspect it is another simple measure that might help strengthen the respiratory muscles. Likewise, strengthening of upper extremity and shoulder girdle musculature can be conducted at home. 8. Derek, D. et al. (2004). Oxford Textbook of Palliative Medicine, pp. 904

Controlled Breathing(8) Purse lipped breathing Improves alveolar ventilation and gas exchange Slow expiration Useful in overcoming associated panic attacks Bending forward position Improves diaphragmatic function through increasing intraabdominal pressure Helps relieve dyspnea Slide 19 details controlled breathing maneuvers that can lessen dyspnea. Again, I suspect that many of us do not emphasize these simple non-pharmacologic methods of reducing dyspnea. Certainly we need to make sure our nurses educate our pulmonary patients as to these maneuvers. 8. Derek, D. et al. (2004). Oxford Textbook of Palliative Medicine, pp. 904

BiPAP (Bilevel Positive Airways Pressure) Reduces time in ICU Reduces need for intubation Reduces mortality in COPD exacerbations Improves quality of life in ALS patients (64) Value of BiPAP in a skilled care setting to “rest” the respiratory muscles is uncertain Slide 20 discusses the advantages of using BiPAP when indicated. While BiPAP may be used at home, most of the time it is a substitute for intubation and a ventilator in a patient with an exacerbation of COPD. Its use in the exacerbation of COPD will certainly reduce the sensation of dyspnea as well as time spent in the ICU, and the need for intubation and use of a ventilator. There are many articles on the use of BiPAP in the treatment of ALS and how it improves the quality of life including a reduction in dyspnea. 8. Derek, D. et al. (2004). Oxford Textbook of Palliative Medicine, pp. 904 64. Neurology Jul 22;61(2):171-7

Summary… Immediate treatment Cold facial stimulation with a fan Controlled cough Forced expiration Pursed lip breathing Slow expiration Bend forward posture Non-immediate treatment Vaccinations – influenza & pneumococcal Nutritional assessment and treatment Addressing emotional, social and spiritual issues Exercise – walking; stair climbing; shoulder girdle strengthening

Palliative Care of Dyspnea Treatment – Pharmacologic
Bronchodilators Antiinflammatories Oxygen Anxiolytics Mucolytics Antidepressants Antibiotics Slide 21 begins the discussion of pharmacologic treatment of dyspnea. As we all know, the end stage pulmonary patient winds up with multiple medications, plus medications to treat the effect of medications. Oxygen is almost always being used as well. Of course, the medication most physicians fail to use for dyspnea in end stage pulmonary patients is also, besides oxygen, the oldest of the listed medications, that of morphine sulfate. ARS-2

Palliative Care of Dyspnea Treatment – Pharmacologic - Bronchodilators
β2 agonists – in COPD Do not necessarily improve FEV1 or FVC Do improve dyspnea Anticholinergics Improve FEV1 Reduce dyspnea Phosphodiesterase Inhibitors Theophylline Leukotriene Antagonists Slide 22 lists the classes of bronchodilators. Note in this slide that the FEV-1 is improved with the use of anticholinergics, but not with beta-2 agonists. Both, however, improve the sensation of dyspnea. As we will see on a subsequent slide, there are new selective phosphodiesterase inhibitors in Phase III trials.

β2 agonists In stable COPD Short acting levalbuterol (Xopenex®) – In stable COPD patients, no advantage over racemic mixture (albuterol) in prn doses(9) Long acting β2 agonists salmeterol (Serevent®), formoterol (Foradil®), arformoterol (Brovana®) Slide 23 addresses beta-2 agonist use in stable COPD. As noted, Xopenex is reported to have no advantage in terms of cardiac side effects over the racemic albuterol. Other references, however, report an advantage over the racemic mixture in cardiac adverse effects when treating asthmatics. Patients with stable COPD should be considered for use of long acting beta-2 agonists in order to reduce episodes of “breakthrough dyspnea” and the need to use the short acting beta-2 agonists. 9. Chest Sep;124(3):844-9

Anticholinergics Short acting – Ipratropium (Atrovent®) Long acting Tiotropium (Spiriva®) Tiotropium (Spiriva®) alone is more effective than long acting β2 agonists alone in COPD patients (10) Tiotropium (Spiriva®) added to a regimen of a long acting β2 agonist and a corticosteroid significantly improved dyspnea, FEV1 and FVC in COPD patients(11) Comparing tiotropium alone to fluticasone/salmeterol/tiotropium therapy showed no difference in rates of COPD exacerbation but the combination therapy did improve lung function, quality of life, and hospitalization rates in patients with moderate to severe COPD.(11a) Slide 24 mentions the anticholinergics. Note that tiotropium or Spiriva alone is more effective than the long acting beta-2 agonists alone in COPD patients. Additionally, if tiotropium is added to a regimen of a long acting beta-2 agonist and a corticosteroid there is significant improvement in dyspnea as well as the FEV-1 and the FVC in COPD patients. 10. Thorax May;58(5): 11. Respirology Sep;11(5): 11a. Annals of Internal Medicine April 17; 146( 8):

Theophylline(12) A non-selective phosphodiesterase (PDE) inhibitor with antiinflammatory and bronchodilatory effects Improves dyspnea Improves FEV1 24 hour sustained release preparation may be given once before bedtime without disturbing sleep (13) Is now used less because of narrow therapeutic range and risks of toxicity. ? Resurgence due to antiinflammatory effects and lower serum levels (<10mg/L).(35a) On the horizon, “Cilomilast and roflumilast are selective PDE4 inhibitors that are currently in pre-registration and phase III clinical trials, respectively, for the treatment of COPD (cilomilast and roflumilast) and for treatment of asthma (roflumilast).”(35) Slide 25 discusses theophylline which has many desirable effects making it an antiinflammatory as well as a bronchodilator. It does improve dyspnea and the FEV-1 and can be given in a once a day preparation. Unfortunately, because of its narrow therapeutic range, toxicity is frequent and costs are generated by the frequent blood levels. With the development of the long acting beta-2 agonists, inhaled steroids, and long acting anticholinergics, the use of theophylline has diminished. In the near future there should be the availability of selective phosphodiesterase 4 inhibitors that should minimize adverse effects of the non-selective theophylline. Cilomilast and roflumilast are both in phase III clinical trials. 12. Derek, D. et al. (2004). Oxford Textbook of Palliative Medicine, pp. 903 13. Chest, Vol 110, 35. Curr Opin Investig Drugs May;7(5):412-7 35a. American Journal of Respiratory and Critical Care Medicine Vol pp , (2003)

Leukotriene Receptor Antagonists Zafirlukast (Accolade®)– Has bronchodilation effect in COPD and asthma There is no additive effect when added to inhaled steroids (34) May reduce pulmonary hypertension in COPD(35) Montelukast (Singulair®) There is long term benefit in elderly COPD patients with moderate to severe disease(36) Slide 26 references two leukotriene receptor antagonists that we are all familiar with. Note that zafirlukast has bronchodilatory effects in COPD and asthma and may reduce pulmonary hypertension in COPD patients. As discussed in future slides, however, the patients with severe COPD and significant pulmonary hypertension are often difficult to identify without the assistance of some high-tech testing which may not be feasible in our end of life patients. Singular, has long term benefit in elderly COPD patients with moderate to severe disease. 34. Pulm Pharmacol Ther. 2000;13(6):301-5 35. Chin Med J (Engl) Mar;116(3):459-61 36. Respir Med Feb;98(2):134-8

Palliative Care of Dyspnea Treatment – Pharmacologic - Antiinflammatories
Corticosteroids in the treatment of COPD / Dyspnea Short term oral corticosteroids: Acute exacerbation of COPD Long term inhaled corticosteroids: Reduces all cause mortality in moderate to severe COPD(14) Not a first line drug in mild COPD(15) Long term oral corticosteroids: Only in those not responding to inhaled corticosteroids Sometimes beneficial in hospice patients with malnutrition Identification of those who will benefit from long term use: Remains controversial One method: Check FEV1 then give a trial of mg prednisone per day for 14 days, then repeat the FEV1. A ≥ 20% increase indicates the patient will benefit from inhaled steroids(16) Slide 27 outlines the use of corticosteroids in the treatment of COPD and dyspnea. The oral corticosteroids are used in exacerbations of COPD, and if treatment of the exacerbation is successful, then the use of inhaled steroids and the discontinuation of the oral preparations. In severe COPD patients oral steroids may have to be continued at the lowest possible dose to avoid Cushingoid adverse effects. Long term inhaled corticosteroids reduce all cause mortality in patients with moderate to severe COPD. Inhaled steroids are not first line drugs in mild COPD. Identification of those COPD patients who will respond to corticosteroids is problematic and remains controversial. One method is to check the FEV-1 before initiation of steroids and then repeat the FEV-1 in 10 to 14 days. If there is improvement, then the patient will likely benefit from corticosteroids. In our end of life patients this is not always practical and most of them come to us already taking an inhaled corticosteroid. I think most of use would not “rock the boat” in this situation and would continue the inhaled steroids. Often the patient on inhaled corticosteroids feels the medication is not beneficial because they do not have the sense of immediate improvement of dyspnea after inhalation of the steroid. Education as to the rationale and use of inhaled corticosteroids is very important to achieve maximal benefit. 14. Thorax Dec;60(12): Epub 2005 Oct 14 15. Curr Opin Pulm Med Mar;10(2):113-9 16. Derek, D. et al. (2004). Oxford Textbook of Palliative Medicine, pp. 903

Palliative Care of Dyspnea Treatment – Pharmacologic - Antiinflammatories
Nebulized Indomethacin May be of value in reduction of mucus secretions in bronchiectasis and chronic bronchitis(52,53) Inhibits production of a proteolytic enzyme, neutrophil elastase May have long term beneficial effect on progression of bronchiectasis Dyspnea was improved(52) Slide 28 notes the use of nebulized indomethacin, a non-steroidal antiinflammatory agent which frankly I have no experience in using it with this route of administration. It is apparently useful in the treatment of chronic bronchitis and bronchiectasis. It works by inhibiting the production of a proteolytic enzyme, neutrophil elastase. Indomethacin may reduce the progression of bronchiectasis. 52. Am Rev Respir Dis Mar;145(3):548-52 53. Eur Respir J Sep;8(9):

Palliative Care of Dyspnea Treatment – Pharmacologic - Oxygen
Indications Resting O2 saturation ≤ 89% with or without dyspnea Those with dyspnea relieved by O2 despite the resting oxygen saturation. Studies have shown ↑ survival with use of long term oxygen, as well as improvement in health related quality of life measures including dyspnea (17,18) The level of O2 saturation does not correlate with the degree of dyspnea (17) Slide 29 discusses the oldest of all of these drugs, oxygen. Oxygen, as we all know is indicated for use in patients who have resting room air oxygen saturations of < 89%. The reason for this guideline is simple. Patients with saturations < 89% will live longer if they use oxygen. Particularly in our patients it is also indicated if it helps in the reduction of dyspnea, despite the level of oxygen saturation. We have all seen patients who seem to not have dyspnea and yet have low saturations. As the slide notes, there is no correlation of the oxygen saturation with the severity of the dyspnea. 17. Derek, D. et al. (2004). Oxford Textbook of Palliative Medicine, pp. 903 18. Curr Opin Pulm Med Mar;10(2):120-7

Palliative Care of Dyspnea Treatment – Pharmacologic - Oxygen
Beware! Patients on oxygen with high oxygen saturation and confusion or lethargy may have C02 retention Treat with discontinuation or reduction in oxygen flow and close observation Titrate to the flow of oxygen that does not cause the confusion or lethargy Slide 30 contains a warning that the patient with a comfortable high oxygen saturation who is receiving oxygen but is lethargic or confused may be retaining carbon dioxide and the oxygen should be temporarily discontinued and the patient closely observed. If the patient’s lethargy and confusion improve the oxygen may be restarted but with at a low flow. The message here is to continue to observe the patient until a new flow level provides the patient with an optimal flow of oxygen that does not result in confusion or lethargy. While all of us are aware of this some of the nurses are not and they should be educated as to this potential complication of oxygen administration.

Palliative Care of Dyspnea Treatment – Pharmacologic - Opioids
Meta-analysis concludes that opioids in modest doses are effective in treating dyspnea(28) Dose – as little as 2.5 mg of MS q4h(29) Sustained release morphine reduces dyspnea(27) (Don’t start on the sustained release forms.) Slide 31 gives supporting references to the use of oral morphine sulfate in the treatment of dyspnea in the end of life pulmonary patient. The rule of start low and go slow applies. 27. BMJ Sep 6;327(7414):523-8 28. Thorax Nov;57(11):939-44 29. Derek, D. et al. (2004). Oxford Textbook of Palliative Medicine, pp. 904

Palliative Care of Dyspnea Treatment – Pharmacologic - Opioids
No clear evidence that inhaled morphine is effective in the relief of dyspnea(30) Slide 32 on the other hand, casts doubt on the use of inhaled morphine sulfate. The bottom line is to use the oral route if at all possible and the result should be better than inhaled morphine. 30. Eur Respir J May;10(5):

Palliative Care of Dyspnea Treatment – Pharmacologic - Anxiolytics
Benzodiazepines Scant literature on the use of benzodiazepines in the treatment of dyspnea but they are commonly used (19, 20) Opioids are first line anxiolytic drugs for dyspnea secondary to advanced disease of any cause(21) Slide 33 emphasizes the fact that morphine sulfate is the first line anxiolytic in the treatment of dyspnea. While benzodiazepines are widely used in the treatment of dyspnea there is not an abundance of supporting literature as to their effectiveness in the treatment of dyspnea. Nevertheless, I am sure all of us will continue to prescribe them. 19. Q J Med Winter;49(193):9-20 20. Am J Hosp Palliat Care Nov-Dec;15(6):322-30 21. Can Fam Physician Dec;49:

Palliative Care of Dyspnea Treatment – Pharmacologic - Anxiolytics
Buspirone (BuSpar®) Conflicting reports of its effect on dyspnea(22,23) Concerns about respiratory depression in COPD patients receiving anxiolytics is unfounded.(24) Anxiolytics can be beneficial in some patients with dyspnea, even those without appreciable anxiety.(24) Slide 34 gives us a bit of good news. Concerns about respiratory depression in COPD patients receiving anxiolytics is unfounded. Again, start low and go slow. While there is conflicting evidence about the beneficial effect of non-opioid anxiolytics, the Oxford Textbook of Palliative Medicine notes that “clinical experience suggests that anxiolytics are beneficial in the treatment of breathlessness”, but lists no references for that opinion. It goes on to say that anxiolytics can be beneficial even in patients without appreciable anxiety, again without references. Despite what the literature says, I think the standard of care is to use anxiolytics in many patients with dyspnea. 22. Respiration. 1993;60(4):216-20 23. Chest Mar;103(3):800-4 24. Derek, D. et al. (2004). Oxford Textbook of Palliative Medicine, pp. 904

Palliative Care of Dyspnea Treatment – Pharmacologic - Mucolytics
N-Acetylcysteine (Mucomyst®) by mouth or inhalation will help patients with excessive or viscous mucous clear these secretions Effect on dyspnea has not been studied Evidence is conflicting as to its reduction of COPD exacerbations(31,32) Slide 35 begins the discussion on mucolytics. N-Acetylcysteine or Mucomyst is useful in patients with excessive or viscous mucous. The effect of this drug on dyspnea has not been studied in the literature. There is controversy about its ability to reduce COPD exacerbations. 31. Lancet Apr 30-May 6;365(9470): 32. Eur Respir J May;21(5):795-8

Palliative Care of Dyspnea Treatment – Pharmacologic - Mucolytics
Additional agents that may assist in mucolysis and expectoration of thick sputum: Normal or hypertonic saline nebulizations Inhaled mannitol powder (66) Inhaled atropine Corticosteroids β2 agonists Indomethacin Theophylline Glycerol guaiacolate Of limited value Slide 36 lists other mucolytic agents. Of note is the use of mannitol powder. This has been used primarily in the treatment of bronchiectasis. Indomethacin has been discussed as an antiinflammatory agent and reduces secretions by a reduction in inflammation. Glycerol guaiacolate has limited value as a mucolytic, though it is a major component of most OTC expectorants and cough syrups. 33. Derek, D. et al. (2004). Oxford Textbook of Palliative Medicine, pp. 904 66. Respirology Jan;10(1):46-56

Palliative Care of Dyspnea Treatment – Pharmacologic - Antidepressants
SSRIs; Tricyclics – In depressed patients with endstage lung disease Beneficial for anxiety Benefit for dyspnea is not conclusive (25,26) Slide 37 addresses the role of antidepressants in the treatment of dyspnea. Evidence is inconclusive, however, in keeping with our goals in end of life care depression is common and should be treated. One would think that if a patient’s depression improves a good number of symptoms would improve. Depression is accompanied by anxiety and is a target symptom of antidepressants. Many of the COPD patients are anxious, and depression should always be a consideration as well as adverse effects from beta-2 agonists or theophylline. 25. Psychosomatics Jan-Feb;39(1):24-9. 26. Derek, D. et al. (2004). Oxford Textbook of Palliative Medicine, pp. 904

Palliative Care of Dyspnea Treatment – Pharmacologic - Antibiotics
Treatment of Exacerbations Antibiotics Fluoroquinolones (37,38) Amoxicillin almost as effective and cheaper(39) Short acting β2 agonists → long acting Short acting anticholinergics → long acting Oral prednisone → Inhaled corticosteroid Slide 38 discusses the treatment of COPD exacerbations which, of course, are accompanied by worsening of dyspnea. Infection is a common reason for an exacerbation of COPD and should be treated with appropriate antibiotics. Fluoroquinolones and amoxicillin are commonly used and a subsequent slide will provide a guideline about which to use in a COPD patient. In addition to antibiotics, short acting beta-2 agonists and anticholinergics in concert with oral prednisone are the mainstays of drug treatment of acute exacerbations. Transition to long acting beta-2 agonists and long acting anticholinergics as well as inhaled corticosteroids should be utilized once the patient stablizes. 37. Clin Microbiol Infect May;12 Suppl 3:42-54 38. Chest Mar;125(3):953-64 39. American Family Physician Vol. 70/No. 4 (August 15, 2004)

Palliative Treatment of Cough
Main Menu…

Palliative Care of Cough Assessment
Many patients will not want the usual diagnostic tests A thorough history and physical examination is often our best and only tool for assessing the cause of the cough ARS-3

Palliative Care of Cough Assessment
Causes Acute infections Chronic Infections Airways Disease Cardiovascular Parenchymal Disease Irritant Recurrent Aspiration Drug Induced Pleural Disease Vocal Cord Disease Examples Pneumonia; Acute Bronchitis Chronic bronchitis; Bronchiectasis COPD; Asthma LV failure; pulmonary edema Interstitial Fibrosis GERD; Foreign body Stroke; Motor neuron disease ACE Inhibitors; inhaled drugs Pneumothorax; pleural effusion Paralysis; nodules on cords Slide 39 is a listing of the non-malignant causes of cough with examples of each cause in the right hand column. 40. Derek, D. et al. (2004). Oxford Textbook of Palliative Medicine, pp. 899

Palliative Care of Cough Treatment of the Underlying Cause
Acute and chronic infections Antibiotics Asthma and COPD Bronchodilators and anti-inflammatories Left ventricular failure Diuretics, ACE inhibitors, ± β- blockers Recurrent aspiration Postioning of patient; swallowing evaluation → alter food consistency Drug induced (ACE inhibitors) Discontinue drug Pleural disease Correct pneumothorax; drain pleural effusion Vocal cord dysfunction ENT evaluation and treatment GERD PPIs; metoclopramide; positioning of patient Post-nasal drip Decongestants; antihistamines Slide 40 outlines the treatment of the more common causes of cough. 40. Derek, D. et al. (2004). Oxford Textbook of Palliative Medicine, pp. 899

Palliative Care of Cough Treatment – Protussive and Antitussive
Protussive Treatments Measures to improve cough effectiveness and secretion clearance Antitussive Treatments Measures to prevent or eliminate cough Slide 41 divides the treatment of cough into two categories, protussive or measures to improve cough effectiveness and secretions, and antitussive or measures to prevent or eliminate cough. 40. Derek, D. et al. (2004). Oxford Textbook of Palliative Medicine, pp. 899

Palliative Care of Cough Treatment – Protussive Treatments
Measures to make cough more effective(40) Adequate hydration – po fluids; steam inhalations; saline nebulizations Physiotherapy – only in select patients with COPD and bronchiectasis (41) Forced exhalations Airways vibrations Postural drainage Assisted cough techniques Slide 42 begins the listing of protussive treatments and includes adequate hydration and physiotherapy. Physiotherapy measures are only effective in select patients with COPD and bronchiectasis in an effort to mobilize excessive sputum. 40. Derek, D. et al. (2004). Oxford Textbook of Palliative Medicine, pp. 899 41. Chron Respir Dis. 2006;3(2):83-91

Measures to make cough more effective(40) Pharyngeal suctioning Mini-tracheostomy For thick, excessive, infected sputum Steroids Antibiotics Inhaled mannitol powder or hypertonic saline (42,43) Slide 43 continues the listing of protussive measures. Again the goal here is to clear secretions from the lung and bronchial airways. 40. Derek, D. et al. (2004). Oxford Textbook of Palliative Medicine, pp. 899 42. Cochrane Database Syst Rev Jul 20;(3):CD001506 43. J Aerosol Med Fall;15(3):331-41

Increase of secretion clearance (40,44) Liquification of secretions N-acetylcysteine Recombinant human DNAse Arginine – not as effective as N-acetylcysteine Uridine-5'-triphosphate – useful for getting sputum samples from mild chronic bronchitics (67) Bronchodilators β2 – agonists (albuterol) Slide 44 refers to several agents that may be utilized to liquify secretions making them easier to expectorate. Arginine is not widely used and is not as effective as Mucomyst. Uridine-5’-triphosphate is useful for obtaining sputum specimens in patients with mild chronic bronchitis. The beta-2 agonists will cause bronchodilation and thus improve sputum yield. 40. Derek, D. et al. (2004). Oxford Textbook of Palliative Medicine, pp. 900 44. Expert Opin Pharmacother Feb;5(2):369-77 67. Chest Dec;122(6):2021-9

Palliative Care of Cough Treatment – Antitussive Treatments
Used when cough is not reversible Used primarily for dry non-productive cough Opioids Oral local anesthetics Nebulized local anesthetics Other antitussive agents Antimuscarinics Slide 45 lists the antitussive agents which are used primarily for non-reversible non-productive coughs. 40. Derek, D. et al. (2004). Oxford Textbook of Palliative Medicine, pp. 900

Antitussive Treatment of Cough
Slide 46 is in ACP Medicine and is an algorithm for the treatment of cough. The dosages of medication are listed as well. ACP Medicine 2006 ARS-4

Opioids Morphine is the strongest antitussive (47) Useful especially in the terminal patient Codeine is used widely In its OTC form codeine has no more antitussive effect than the demulcent vehicle (47) Dextromethorphan – an opioid derivative No analgesic effect in antitussive doses As effective as codeine for cough suppression Slide 47 outlines the opioids used for antitussive purposes. As you can see, our old friend morphine sulfate is the most potent of the opioid antitussives. Codeine is also effective, however, in its OTC mixture it has no more antitussive effect than the demulcent vehicle. Dextromethorphan is an opioid derivative without analgesic effect in doses used to suppress cough. It is as effective as codeine for cough suppression. 45. Chest Jan;129(1 Suppl):284S-286S 46. Pulm Pharmacol Ther. 2004;17(6):459-62 47. Thorax May;59(5):438-40 45. Chest Jan;129(1 Suppl):284S-286S 46. Pulm Pharmacol Ther. 2004;17(6):459-62 47. Thorax May;59(5):438-40

Oral Local Anesthetics Benzonatate (Tessalon Perles ®) Peripheral acting / opiates largely central acting Often effective in opiate resistant cough (47) Levodropropizine – not available in USA Widely used in Europe Peripheral acting and useful in cancer related cough (47) Slide 48 includes two oral local anesthetics, only one of which is available in the USA. Tessalon Perles are peripheral acting whereas opiates are centrally acting. In patients who are not responding to opiates, you should consider the Tessalon Perles. The greatest benefit to having levodropropizine would be a welcome addition to the USA as it apparently is quite beneficial in treatment of cough related to lung cancer. 45. Chest Jan;129(1 Suppl):284S-286S 46. Pulm Pharmacol Ther. 2004;17(6):459-62 47. Thorax May;59(5):438-40

Nebulized Local Anesthetics Risk is aspiration 2-4 hours after a treatment Patient should not eat or drink for 1 hour after Rx Nebulized lidocaine is effective in reduction of cough (48, 49) (5mg/kg in normal saline) Bupivacaine and Lidocaine have been associated with bronchoconstriction in patients with reactive airways. Consider giving with salmeterol (50) Slide 49 mentions nebulized local anesthetics. The principal risks of using these medications are the potential to aspirate and the occasional patient with asthma that has resultant bronchospasm. Some experts advise administration of salmeterol with bupivacaine or lidocaine to reduce the risk of bronchoconstriction. In order to reduce the risk of aspiration, the patient should be instructed not to eat or drink for at least two hours after a treatment. 48. Am J Emerg Med May;19(3):206-7 49. Emerg Med J Jun;22(6):429-32 50. Canadian Family Physician. May 2002

Other Antitussive Agents If cause is bronchospasm, inflammation, or tumor… Theophylline β2 –agonists Anti-inflammatories Steroids Sodium cromoglycate Slide 50 points out the importance of treating the underlying cause of the cough. Sometimes with terminal patients we are not able to identify the cause of the cough and an appropriate shotgun approach may be necessary. 40. Derek, D. et al. (2004). Oxford Textbook of Palliative Medicine, pp. 901

Other Antitussive Agents OTC Marketed as Antitussive but Not Proven Effective Pseudoephedrine Dexbrompheniramine Guaifenesin Slide 51 shows three medications that are often found in OTC preparations, however, none have been shown to be effective as marketed. 40. Derek, D. et al. (2004). Oxford Textbook of Palliative Medicine, pp. 901

Antimuscarinics Ipratropium bromide Good in chronic bronchitis Reduces secretions without reduction in mucus viscosity Hyoscine .2-.4mg sc prn or Glycopyrronium bromide mg IM prn Good for the death rattle and associated cough May cause ataxia and hallucinations in the elderly Slide 53 identifies two antimuscarinics used in the treatment of a loose cough. Ipratropium bromide is able to reduce secretions without reduction in the viscosity of the sputum, making it a good choice for chronic bronchitis. Hyoscine or glycopyrronium bromide are useful in treatment of the death rattle, though may cause ataxia, confusion and hallucinations in the elderly patient. 40. Derek, D. et al. (2004). Oxford Textbook of Palliative Medicine, pp. 901

Antimuscarinics (68) Ophthalmic Atropine 1% drops Give sublingually or po Scopolamine Patch ® Hyoscine in a patch Not effective for about 12 hours Slide 53 includes two other methods of controlling the death rattle. While the Scopolamine Patch is convenient it does not become fully effective for about 12 hours after application, which is often times several hours after death. Ophthalmic atropine drops have a rapid onset and may be given sublingually. 68. AAHPC Fast Fact and Concept #109: Death rattle and oral secretions

Palliative Care of Respiratory Infections

Palliative Care of Respiratory Infections Treatment – Establishing Goals
Above all - goals must be discussed and formulated with the patient and family The patient or POA may ultimately decide against antibiotic therapy If antibiotics are not chosen as a treatment, symptomatic treatment of fever, dyspnea and cough should be the plan In Slide 54 pulmonary infections are addressed. Of most importance are having good conversations with the patient and/or the POA about the goals of treatment. Especially this is true with patients with recurrent aspiration and a very poor quality of life or the COPD patient who is having multiple exacerbations. Should antibiotics not be chosen, there is still lots to do in treating the symptoms of infection.

Palliative Care of Respiratory Infections Treatment – Antibiotic Selection
COPD with FEV1 < 50% (Most hospice patients with end stage lung disease) exacerbations should be treated with a quinolone COPD with FEV1 > 50% use ampicillin, tetracycline or trimethoprim/sulfa Slide 55 provides guidelines as to the selection of antibiotics in exacerbations of COPD. Of course, often times we don’t have access to results of our patient’s PFTs. While an FEV-1 is not required for eligibility, the Medicare guidelines suggest an FEV-1 of < 30% after bronchodilator. On this basis the patient receiving the hospice benefit with terminal lung disease probably has an FEV-1 of < 50% and should, therefore, receive the quinolone 51. ACP Medicine Chapter 14:Respiratory Medicine: III Chronic Obstructive Disease of the Lung

Bronchiectasis and Cystic Fibrosis Coverage of anaerobic bacteria and pseudomonas are important Antibiotics should be given in high doses, sometimes rotated and for 3-4 week courses Ciprofloxacin Metronidazole Augmentin In slide 56 the special antibiotic needs of bronchiectasis and cystic fibrosis patients are discussed. Because of the frequency of pseudomonas infections, ciprofloxacin, metronidazole and Augmentin are recommended with 3-4 week courses and rotation of antibiotics from one episode of infection to another. 40. Derek, D. et al. (2004). Oxford Textbook of Palliative Medicine, pp. 901

Bronchiectasis and Cystic Fibrosis Nebulized antibiotics Gentamicin (300 mg bid) Tobramycin (300 mg bid) Slide 57 points out that there is a role for nebulized aminoglycosides in patients with bronchiectasis or cystic fibrosis. 40. Derek, D. et al. (2004). Oxford Textbook of Palliative Medicine, pp. 901

Palliative Care of Hemoptysis

Palliative Treatment of Hemoptysis Assessment
Majority of cases are mild to moderate <20% are massive (> 500 cc per day) Most common causes Infection ~ 80% TB Abscesses Bronchiectasis Malignancy ~ 20% Hemoptysis, another frightening complication of advanced lung disease, is covered in slide 60. Most often hemoptysis is not massive, defined as > 500 cc per day. Of the non-malignant causes of hemoptysis the most frequent are cavitary TB, abscesses, and bronchiectasis. Malignancy accounts for about 20 % of the patients with hemoptysis. 40. Derek, D. et al. (2004). Oxford Textbook of Palliative Medicine, pp. 901

Palliative Treatment of Hemoptysis Assessment
History and Physical Examination Examination of the sputum Presence of food particles Hematemesis T/E fistula Purulent sputum Infection Laboratory and X-Ray Studies Chest x-ray CT with contrast Bronchial artery or pulmonary artery arteriogram Slide 61 addresses the evaluation of hemoptysis. Often times the only information we have is from a good history and physical examination. If food particles are seen in the bloody sputum, one must think of hematemesis or a T/E fistula. Of course, purulent bloody sputum points to an infectious cause. Ideally a chest x-ray, CT with contrast, and bronchial and pulmonary arteriography, and bronchoscopy should be done to identify the cause. In our hospice patients these studies are often not practical to accomplish. 40. Derek, D. et al. (2004). Oxford Textbook of Palliative Medicine, pp. 901

Palliative Treatment of Hemoptysis Treatment - Anticipatory
Anticipation - If resuscitation is or is not the goal Education of patient, family and caregivers Goals must be established Dark colored towels Morphine Anxiolytics Lorazepam Diazepam Midazolam Slide 62 discusses the management of massive hemoptysis. The most important thing we can do for patients at risk of hemoptysis, is to anticipate massive hemoptysis. This includes the patient, family and caregiver having unified goals, and coaching those living with the patient as to what to do if massive hemoptysis occurs. If possible there should be quick access to morphine and anxiolytics in an emergency pack. 40. Derek, D. et al. (2004). Oxford Textbook of Palliative Medicine, pp. 901

Palliative Treatment of Hemoptysis Treatment of Massive Hemoptysis
If resuscitation is the goal… Patent airway + oxygen Intubation and ventilation if needed Position Lateral decubitus Head down Bleeding lung down Determine the site of bleeding Avoid excessive manipulation Cough suppression (codeine mg po q6h) Assuming the patient wants aggressive treatment slide 64 lists the steps to take when massive hemoptysis occurs. Once a patent airway is maintained and oxygen administered, the patient should be placed in the lateral decubitus position with the bleeding side dependent. Then the site of the bleeding should be determined as previously described. Excessive manipulation should be avoided and a cough suppressant can be given if indicated. 40. Derek, D. et al. (2004). Oxford Textbook of Palliative Medicine, pp. 901

Palliative Treatment of Hemoptysis Treatment of Massive Hemoptysis – Goal Resuscitation
If resuscitation is the goal…(continued) Immediate bronchoscopy If source identified, lavage with iced saline and adrenalin (10cc of 1:10,000 dilution) Topical thrombin Balloon catheter tamponade Vasopressin Bronchial stent placement If source not found CT with contrast Bronchial or pulmonary angiography Slide 64 discusses the treatment of massive hemoptysis assuming that aggressive treatment has been chosen by the patient. Since many of our patients are at home, this often will be difficult to execute. Immediate bronchoscopy should be done to identify the source of bleeding and to stop the bleeding using a variety of techniques. If the source is not discovered and the patient is still alive, CT with contrast should be done and if the site is still in question, bronchial arterial and / or pulmonary angiography should follow. 40. Derek, D. et al. (2004). Oxford Textbook of Palliative Medicine, pp. 901

Palliative Treatment of Hemoptysis Treatment of Massive Hemoptysis – Goal Resuscitation
If resuscitation is the goal…(continued) Bronchial arterial embolization Successful in % of cases Especially good in those with dilated bronchial arteries (bronchiectasis) Complications Rebleeding - common Anterior spinal artery infarction and paraplegia – 5% Ischemic necrosis of the bronchus Arterial dissection Surgical resection of the bleeding tissue Bronchial arterial embolization is discussed on slide 65. It is successful in stopping the massive hemoptysis in 70 to 100% of patients. Bronchiectasis is often associated with dilated bronchial arteries and bronchial artery arteriograms followed by embolization can be very useful. Dreaded complications include not only rebleeding, but also thrombosis of the anterior spinal artery with resultant paraplegia in 5% of patients, ischemic necrosis of the bronchus and arterial dissection. If not successful, the next step is surgical resection of the bleeding tissue. 40. Derek, D. et al. (2004). Oxford Textbook of Palliative Medicine, pp. 901

Palliative Care of Pulmonary Hypertension and Cor Pulmonale

Palliative Care of Pulmonary Hypertension and Cor Pulmonale
Clinical Manifestations Dependent edema Right ventricular hypertrophy Right ventricular dilatation The manifestations of pulmonary hypertension and cor pulmonale are listed in slide 68. These we are all familiar with. ARS-5

Palliative Care of Pulmonary Hypertension and Cor Pulmonale Etiology and Pathophysiology
Most chronic pulmonary diseases can ultimately cause pulmonary hypertension and cor pulmonale Pathophysiology (56) COPD – severe pulmonary hypertension only in a small percentage of COPD patients Hypoxia → constriction of pulmonary arterial vasculature – However… Poor correlation between arterial p02 and pulmonary artery pressure in COPD Chronic inflammation Repeated hyperinflation of the lungs Cigarette smoking Pulmonary Emboli and Pulmonary Fibrosis Obstruction of the pulmonary vasculature Primary Pulmonary Hypertension Etiology unknown Slide 66 begins the discussion about pulmonary hypertension and cor pulmonale. Of course most chronic pulmonary diseases are capable of causing pulmonary hypertension and cor pulmonale, however, in COPD patients severe pulmonary hypertension occurs only in a small percentage of patients. In addition to the hypoxic pulmonary arterial vasoconstriction, chronic inflammation, cigarette smoking and repeated hyperinflation of the lungs contribute to production of pulmonary arterial hypertension. Interestingly, there is a poor correlation between the arterial oxygen tension and pulmonary artery pressure in COPD patients. Obstruction of the pulmonary vasculature as in pulmonary emboli and pulmonary fibrosis can result in pulmonary hypertension. Of course, the poorly understood entity of primary pulmonary hypertension causes cor pulmonale. 40. Derek, D. et al. (2004). Oxford Textbook of Palliative Medicine, pp. 909 56. The Proceedings of the American Thoracic Society 2:20-22 (2005)

Pathophysiology of Edema in COPD
Palliative Care of Pulmonary Hypertension and Cor Pulmonale Pathophysiology Pathophysiology of Edema in COPD Exercise → ↑ right ventricular end diastolic pressure → ↑ stretching of the right atrium → ↑ sympathetic tone → ↑ renin angiotensin aldosterone production → ↑ renal distal tubular retention of water and sodium → ↑ edema (56) C02 retention → ↑ renal proximal tubular sodium retention → ↑ edema Slide 67 displays the cascade of pathophysiologic events leading to pulmonary hypertension in COPD patients. The two major triggers are exercise and CO2 retention. Do not conclude from this slide that COPD patients should not exercise. The thing to take away from this slide is that the renin, angiotensin, aldosterone sequence plays a major role in the development of edema and ultimately pulmonary hypertension in COPD patients. 56. The Proceedings of the American Thoracic Society 2:20-22 (2005)

Palliative Care of Pulmonary Hypertension and Cor Pulmonale Treatment
Treat the underlying pulmonary disease Oxygen Long term oxygen therapy in COPD Only produces a small decrease in pulmonary artery pressure In acute exacerbations of COPD Delivered with BiPAP , reduces pulmonary artery pressure Slide 69 outlines the treatment of pulmonary hypertension and cor pulmonale. First, treat the underlying cause. In COPD long term treatment with oxygen when indicated will help, and prevention and appropriate treatment of COPD exacerbations will help in treating cor pulmonale. 40. Derek, D. et al. (2004). Oxford Textbook of Palliative Medicine, pp. 909

β2 – agonists Reduce pulmonary artery pressure Increase right ventricular ejection fraction Diuretics – the primary treatment of edema Edema is secondary to – Hypoxic renal dysfunction Excessive release of pituitary hormones Not caused by right heart failure Caution: hypochloremic alkalosis → ↓ ventilation and C02 retention Calcium Channel Blockers Only short term effect on pulmonary hypertension May produce ventilation-perfusion mismatch and worsen oxygen saturation May produce systemic hypotension As shown in slide 70, beta-2 agonists reduce pulmonary arterial pressure and stimulate right ventricular contractile force. Edema in cor pulmonale is more a consequence of the renin, angiotensin, aldosterone production than the increased pressures of right ventricular heart failure. So we are seeing lots of COPD patients with edema and mild pulmonary hypertension, but not severe pulmonary arterial hypertension. There were great expectations for calcium channel blockers in the treatment of pulmonary hypertension, but the effects are short lived and long term use may even be somewhat detrimental in that V/Q miss-matching may occur resulting in a reduction of arterial oxygen levels, and, of course systemic hypotension may result as well. 40. Derek, D. et al. (2004). Oxford Textbook of Palliative Medicine, pp. 909

ACE Inhibitors Cause systemic hypotension No improvement in pulmonary vascular resistance, gas exchange or ventilatory parameters For completeness, in slide 71, ACE inhibitors are of no value in treating pulmonary hypertension. 40. Derek, D. et al. (2004). Oxford Textbook of Palliative Medicine, pp. 909

Palliative Care of Primary Pulmonary Hypertension

Palliative Care of Primary Pulmonary Hypertension Treatment
Endothelin antagonists Bosentan (Tracleer®) (57) – Oral endothelin receptor blocker Mild improvement in dyspnea 36 meter increase in 6 minute walking distance Approved for use in pulmonary arterial hypertension May be used in patients with COPD and severe pulmonary hypertension, but these patients are difficult to identify in an end of life setting. Clinical trials are ongoing.(58) Caution – Numerous drug interactions Slide 72 addresses use of the endothelin antagonist bosentan or Tracleer. The good news is that it is an oral medication and improves dyspnea in patients with pulmonary hypertension. The bad news is that the bulk of our patients are COPD patients without severe pulmonary hypertension. COPD patients with severe pulmonary hypertension are not easily identified. Only about 10 % of COPD patients have significant pulmonary hypertension. Bosentan has numerous drug interactions so before prescribing, be sure there will be no drug interactions. Before considering this drug in COPD it is best to have objective evidence of pulmonary hypertension such as pulmonary artery pressures and evidence of right ventricular hypertrophy. 57. U.S. Pharmacist Vol. No: 30:05 Posted: 5/16/05 58. Curr Opin Pulm Med Mar;9(2):139-43

Prostacyclin Analogs Epoprostenol (Flolan®) and Treprostinil (Remodulin®) Improves exercise tolerance Must be given as a continuous infusion Iloprost (Ventavis®) Inhaled Beraprost – Not available in USA Improvement in symptoms The prostacyclin analogs are mentioned in slide 73. Epoprostenol and treprostinil both have to be given as a continuous infusion but both improve exercise tolerance. Iloprost is inhaled making it a more practical drug to use in the treatment of primary pulmonary hypertension. 57. U.S. Pharmacist Vol. No: 30:05 Posted: 5/16/05

Phosphodiesterase V Inhibitors Sildenafil (Viagra®) Improves exercise tolerance Other phosphodiesterase V inhibitors are being evaluated Tadalafil (Cialis®) – only once daily dosing Anticoagulants Warfarin – To prevent microthrombi formation in pulmonary circulation To prevent thrombophlebitis in the lower extremities Keep INR at Reduces progression of the disease and those symptoms that will worsen with progression of the disease Slide 74 mentions the phosphodiesterase V inhibitors, specifically Viagra and Cialis both of which improve exercise tolerance in primary pulmonary hypertension. Patients with primary pulmonary hypertension are at high risk of thrombophlebitis and thromboembolism. INR should be kept in the 1.5 – 2.0 range. Warfarin reduces progression of the disease and the symptoms of primary pulmonary hypertension. 57. U.S. Pharmacist Vol. No: 30:05 Posted: 5/16/05

Palliative Care of Pulmonary Fibrosis

Palliative Care of Pulmonary Fibrosis Treatment
Pneumoconioses – Most Common Cause Idiopathic Pulmonary Fibrosis Treatment with interferon gamma-1b Conflicting evidence of effectiveness (59,60) Metaanalysis suggests it does prolong life ( 61) In general pulmonary fibrosis patients do not retain CO2 High flows of oxygen may be used Pulmonary fibrosis is mentioned in slide 75. Pneumoconioses is the leading cause. For idiopathic pulmonary fibrosis interferon gamma-1b has been used but with conflicting evidence of effectiveness and no prolongation of life. The important thing to take away from this slide is that in general patients with pulmonary fibrosis are not CO2 retainers and high flows of oxygen may be used to help their dyspnea. 59. Mayo Clin Proc Sep;78(9):1082-7 60. Ann Pharmacother Oct;39(10): Epub 2005 Sep 13 61. Chest Jul;128(1):203-6

Palliative Care of Pulmonary Emboli

Most deaths from PE are a result of inadequate prophylaxis Which end of life patients should receive prophylaxis? End stage cardiopulmonary patients Cancer patients with prothrombotic tumors Minimal data on prophylactic treatment VTE in end of life outpatients Slide 79 addresses a difficult issue in many of our hospice patients, that of prophylactic anticoagulation. As noted most deaths from pulmonary emboli are a result of inadequate prophylaxis. End stage cardiopulmonary patients, immobile patients, and patients with prothrombotic tumors are all candidates for anticoagulants and many are at high risk of bleeding from such therapy.

Current VTE Prophylaxis Hydration Not crossing legs Traditional stockings probably not effective Encouraging mobility Drug therapy Low molecular weight heparin is preferred No prothrombin time needed Once daily injection Warfarin INR should be 2-3 Difficult to regulate in the end of life patient because of other drug therapies and fluctuating liver functions Slide 80 lists the measures to prevent venous thromboembolism. Noteworthy is that traditional stockings are probably not effective and that low molecular weight heparin is preferred over warfarin since laboratory monitoring is not needed. Warfarin is difficult to regulate in the end of life patient because of other drug therapies and in some patients fluctuating liver functions.

On the horizon… Ximelagatran Oral medication As effective as low dose warfarin with enoxaparin Not yet approved because of potential hepatotoxicity and ↑ incidence of coronary events Idraparinux Once weekly injection In phase III trials Slide 82 flashes some hope for two new anticoagulants for prevention of venous thromboembolism and pulmonary emboli. Ximelgatran is an oral medication which is effective, but not yet approved by the FDA because of potential hepatotoxicity and coronary events. Another attractive prospect on the horizon is Idaparinux, a once a week injection not requiring laboratory monitoring. 62. Semin Vasc Med Aug;5(3):276-84

Palliative Care of Stridor

Palliative Treatment of Stridor
Causes Infection – epiglottitis, diphtheria Tumor Aspirated objects Thick sputum Blood clots Foreign bodies Dislodged tumor particles Crohn's Disease – rare – resistant to dexamethasone (54) Diffuse Idiopathic Skeletal Hyperostosis (DISH) Forestier’s Disease – from large cervical spine osteophytes compressing the trachea (55) Achalasia – megaesophagus compression of trachea (56) Myasthenia gravis – presenting with exertional stridor (57) Psychogenic stridor (58) Drug hypersensitivity – amphotericin (60) Stridor is presented in slide 58. Some unusual causes of stridor are listed. While this presentation does not include malignant pulmonary disease, neoplasm or aspiration are probably the most common causes of in our hospice patients. 40. Derek, D. et al. (2004). Oxford Textbook of Palliative Medicine, pp. 902 54. Chest Aug;130(2):579-81 55. J Laryngol Otol Jan;113(1):65-7 56. Eur J Gastroenterol Hepatol Nov;9(11):1125-8 57. Thorax Jan;51(1):108-9 59. Gen Hosp Psychiatry May;16(3):213-23 60. Ann Allergy Asthma Immunol Nov;91(5):460-6

Palliative Treatment of Stridor Treatment – Non-pharmacologic and Pharmacologic
Postural manipulation Heimlich maneuver – for acute onset stridor Physiotherapy Bronchoscopy or laryngoscopy Tracheostomy Stents Medications Dexamethasone 16 mg po qd for edema or inflammation Oxygen / Helium 4:1 Mixture Infliximab – for Crohn’s Disease (54) Slide 59 outlines the treatment of stridor. We must not forget the Heimlich maneuver may be appropriate in our hospice patients who are so prone to dysphagia and recurrent aspiration resulting in stridor. In those patients in whom a quick fix is not possible endoscopy and tracheostomy can be offered. Medical treatments include an oxygen helium mixture and administration of dexamethasone. Crohn’s disease as a cause is very unusual, but I thought interesting, and apparently resistant to corticosteroids but responsive to infliximab. 40. Derek, D. et al. (2004). Oxford Textbook of Palliative Medicine, pp. 902 54. Chest Aug;130(2):579-81

Palliative Care of Neuromuscular and Restrictive Pulmonary Disorders

Palliative Care of Neuromuscular Disorders and Restrictive Pulmonary Disease
Hypercapnia and sleep disorders are very common in neuromuscular disorders MS and ALS – bulbar disorders result in dysphagia and frequent aspiration and pneumonia Long term anticoagulation is often prescribed for thromboembolic prophylaxis Glossopharyngeal breathing is a good technique to improve ventilation in patients with high cervical injuries Slide 76 touches on neuromuscular and restrictive pulmonary diseases. Hypercapnia and sleep disorders are common in ALS and MS. Thromboembolic prophylaxis are important in these patients. Glossopharyngeal breathing can improve ventilation in patients with high cervical injuries.

Non-invasive mechanical ventilation
Palliative Care of Neuromuscular Disorders and Restrictive Pulmonary Disease Non-invasive mechanical ventilation Rocking beds Abdominal pneumatic belts Negative pressure ventilators Nasal CPAP Slide 77 lists the non-invasive methods for mechanical ventilation in patients with neuromuscular disease and hypoventilation. These, of course, can improve the sensation of dyspnea.

Palliative Care of Bronchiectasis and Cystic Fibrosis

Palliative Care of Bronchiectasis and Pulmonary Fibrosis
Nebulized Deoxyribonuclease (DNAse) Hydrolysis of extranuclear DNA that accumulates with neutrophil degradation in infected airways Useful in cystic fibrosis and to a lesser extent in bronchiectasis Slide 78 mentions that in bronchiectasis and in cystic fibrosis, the mucous contains large numbers of neutrophils because of the chronically infected bronchi. This results in large amounts of extranuclear DNA and tenacious sputum. The use of nebulized DNAse to hydrolyze intra-airway extranuclear DNA has proven useful in the treatment of bronchiectasis and cystic fibrosis. 40. Derek, D. et al. (2004). Oxford Textbook of Palliative Medicine, pp. 908

Palliative Care of α-1 Antitrypsin Deficiency

Palliative Care of α-1 Antitrypsin Deficiency
“AAT replacement therapy is for enzyme deficient patients with impaired FEV-1 (35-65% of predicted value), who have quit smoking and are on optimal medical therapy but continue to show a rapid decline in FEV-1 after a period of observation of at least 18 months.”(63) Treatment of lung disease caused by Alpha-1 antitrypsin deficiency is summarized in a quote on slide 83. Not every patient with alpha-1 antitrypsin deficiency needs to receive enzyme therapy. 63. Treat Respir Med. 2005;4(1):1-8

Happy Trails from Lea County, NM

Links - 1 Spiriva Cost Spiriva vs. Serevent
Respiratory Sep;11(5): Is a long-acting inhaled bronchodilator the first agent to use in stable chronic obstructive pulmonary disease? Emerging drugs for the treatment of chronic obstructive pulmonary disease. Pharmacologic treatment of chronic obstructive pulmonary disease: past, present, and future. Names of leukotriene related drugs Effect of Intravenous Magnesium Sulfate on Chronic Obstructive Pulmonary Disease Addition of anticholinergic solution prolongs bronchodilator effect of beta 2 agonists Comparison of the bronchodilating effect of salmeterol and zafirlukast in combination Retrospective evaluation of systemic corticosteroids for the management of acute exacerbations Efficacy and safety of inhaled corticosteroids in patients with COPD Roflumilast for the treatment of chronic obstructive pulmonary disease Corticosteroids and Chronic Obstructive Pulmonary Disease Theophylline in chronic obstructive pulmonary disease: new horizons. Corticosteroid resistance in chronic obstructive pulmonary disease: inactivation of histone deacetylase. Inhaled corticosteroids and mortality in chronic obstructive pulmonary disease. Inhaled corticosteroids in chronic obstructive pulmonary disease: is there a long-term benefit? Health-related quality of life in individuals with chronic obstructive pulmonary disease. Improving health-related quality of life in chronic obstructive pulmonary disease.

Links - 2 Diazepam in the treatment of dyspnea in the 'Pink Puffer' syndrome. The palliation of dyspnea in terminal disease More research needed An approach to dyspnea in advanced disease. Opioids are first line drugs Buspirone effect on breathlessness and exercise performance in patients with chronic obstructive pulmonary disease. Effects of buspirone on anxiety levels and exercise tolerance in patients with chronic airflow obstruction and mild anxiety. Sertraline effects on dyspnea in patients with obstructive airways disease Randomized, double blind, placebo controlled crossover trial of sustained release morphine for the management of refractory dyspnea A systematic review of the use of opioids in the management of dyspnea Disabling dyspnea in patients with advanced disease: lack of effect of nebulized morphine Roflumilast for the treatment of chronic obstructive pulmonary disease Effects of N-acetylcysteine on outcomes in chronic obstructive pulmonary disease (Bronchitis Randomized on NAC Cost-Utility Study, BRONCUS): a randomized placebo-controlled trial N-acetylcysteine reduces the risk of re-hospitalization among patients with chronic obstructive pulmonary disease Short-term effects of montelukast in stable patients with moderate to severe COPD Therapeutic responses in asthma and COPD. Bronchodilators Review of effects of PDE4 Inhibitors and LRAs Long-term montelukast therapy in moderate to severe COPD--a preliminary observation Current and future pharmacologic therapy of exacerbations in chronic obstructive pulmonary disease and asthma. Should patients with acute exacerbation of chronic bronchitis be treated with antibiotics? Advantages of the use of fluoroquinolones.

Links - 3 Short-term and long-term outcomes of moxifloxacin compared to standard antibiotic treatment in acute exacerbations of chronic bronchitis Moxifloxacin vs. Alternatives for Chronic Bronchitis Palliative Home Care for Advanced Lung Disease Is there a role for airway clearance techniques in chronic obstructive pulmonary disease? Nebulized hypertonic saline for cystic fibrosis Osmotic stimuli increase clearance of mucus in patients with mucociliary dysfunction Potential future therapies for the management of cough: ACCP evidence-based clinical practice guidelines Potential new cough therapies. Current and future drugs for the treatment of chronic cough Comparison of lidocaine and bronchodilator inhalation treatments for cough suppression in patients with chronic obstructive pulmonary disease. Lidocaine inhalation for cough suppression Effect of indomethacin on bronchorrhea in patients with chronic bronchitis, diffuse panbronchiolitis, or bronchiectasis In vivo study of indomethacin in bronchiectasis: effect on neutrophil function and lung secretion Stridor in Crohn disease and the use of infliximab

Links - 4 An unusual case of stridor due to osteophytes of the cervical spine: (Forestier's disease). Myasthenia gravis presenting with stridor Achalasia presenting as acute stridor Psychogenic stridor Amphotericin-induced stridor: a review of stridor, amphotericin preparations, and their immunoregulatory effects Use of the Dumon Y-stent in the management of malignant disease involving the carina: a retrospective review of 86 patients Thoracic embolotherapy for life-threatening hemoptysis: a pulmonologists perspective Bronchial and non bronchial systemic artery embolization for life-threatening hemoptysis: a comprehensive review Pulmonary hypertension and right heart failure in chronic obstructive pulmonary disease Advances in the treatment of secondary pulmonary hypertension Overview of treprostinil sodium for the treatment of pulmonary arterial hypertension Sildenafil for pulmonary hypertension Oral sildenafil is an effective and specific pulmonary vasodilator in patients with pulmonary arterial hypertension: comparison with inhaled nitric oxide Treatment of Pulmonary Hypertension Interferon gamma-1b as therapy for idiopathic pulmonary fibrosis. An intra-patient analysis. Interferon gamma-1b therapy for advanced idiopathic pulmonary fibrosis Interferon gamma-1b in the treatment of idiopathic pulmonary fibrosis Interferon-gamma1b therapy in idiopathic pulmonary fibrosis: a metaanalysis Emphysema in alpha1-antitrypsin deficiency: does replacement therapy affect outcome? Ximelagatran vs low-molecular-weight heparin and warfarin for the treatment of deep vein thrombosis: a randomized trial.

Links - 5 Is long-term low-molecular-weight heparin acceptable to palliative care patients in the treatment of cancer related venous thromboembolism? A qualitative study. Acceptability of low molecular weight heparin thromboprophylaxis for inpatients receiving palliative care: qualitative study. Treating patients with venous thromboembolism: initial strategies and long-term secondary prevention. Inhaled mannitol for the treatment of mucociliary dysfunction in patients with bronchiectasis: effect on lung function, health status and sputum. Improved sputum expectoration following a single dose of INS316 in patients with chronic bronchitis.

Palliative Care of Respiratory Symptoms

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Palliative Care of Respiratory Symptoms

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