304
Canadian Family Physician•Le Médecin de famille canadien|
Vol 57: March • Mars 2011Palliative Care Files
Margaret, a 67-year-old woman with a long smoking history, presents to you with dyspnea, cough with hemoptysis, fatigue, and weight loss, as well as low back and left hip pain. On examination, you find absent air entry in her right lower lobe, dull- ness to percussion, and a generalized expiratory wheeze. She has tenderness in her lumbar spine with limited mobility due to back pain, and subtle right-sided weakness and dysarthria. During the office visit you address her pain and ask her to return for a follow-up appointment to reassess her pain and make arrangements for investigations.
Investigations reveal a right lung mass with multiple lung nodules, mediastinal adenopathy, metastatic brain disease, and metas- tases to the fourth and fifth lumbar vertebrae and the left proximal femur. Percutaneous lung biopsy results give a tissue diagnosis of small cell lung cancer. With the confirmed tissue diagnosis and advanced metastatic disease, she was staged as having extensive- stage small cell lung cancer. Margaret, like many of our patients, has multiple medical comorbidities: hypertension, angina (no history of myocardial infarction), atrial fibrillation with a pacemaker, osteoporosis,
hyperlipidemia, and type 2 diabetes mellitus. She takes several medications: 15 mg of ramipril daily, 25 mg of hydrochlorothiazide daily, 50 mg of metoprolol twice daily, 4 mg of warfarin daily, 500 mg of metformin twice daily, 20 mg of atorvastatin daily, 70 mg of alendronate weekly, and nitroglycerin spray as required.
There are 2 stages of small cell lung cancer. Limited-stage small cell lung cancer is present in only one lung and might have metastasized to nearby lymph nodes or to the mediastinum, but not to other regions of the body.
Extensive-stage lung cancer is present when the cancer has metastasized to another lobe of the lung or there are distant metastases. The prognosis is poor; the overall survival rate is only about 6%. For extensive-stage small cell lung cancer, the median survival is 6 to 12 months with treatment, and 2 to 4 months with no treatment. Small cell lung cancer is almost always con- sidered inoperable.1
Goals of care
Margaret is married and lives with her husband of 43 years; they were unable to have children. She is a retired office receptionist, and her hus- band has retired from the military. They live in their own home. They have a few close friends and there are no family members living in their area.
Margaret and her husband return to discuss the diagnosis and prognosis.
It is a very difficult conversation and they are both overwhelmed by the news.
You refer her to an oncologist to further discuss the diagnosis, prognosis, and options for treatment. She is informed of the potential side effects and sub- stantial morbidity that might result with treatment. After much thought and angst, given the poor prognosis with or without treatment, she decides to forgo any further life-prolonging treatment.
As physicians we need to be aware of patients’ spiritual, religious, and cultural beliefs, as these factors might affect their decision making when it comes to withdrawing or withholding medication or other treatments at the end of life. When initiating these discussions, the decisions to decline
Withdrawing medication
Managing medical comorbidities near the end of life
Christopher P. O’Brien
MD CCFP FCFPBottom line
• Family physicians need to initiate
discussions about medication withdrawal and goals of care with patients with limited life expectancy.
• Patients’ decision making about declining treatment or withdrawing medication might occur all at once or might take place over time, with specific treatments, medications, and devices being gradually withdrawn.
• Frequent review of and amendments to goals of care are necessary when managing medical comorbidities. The need for certain medications, as well as their route and time of administration, should be evaluated regularly.
PointS De RePÈRe
• Les médecins de famille doivent entamer des discussions sur la cessation de la médication et les objectifs des soins avec les patients dont l’espérance de vie est limitée.
• La décision des patients au sujet du refus des traitements ou de la cessation de la médication peut se produire en une seule fois ou se prendre avec le temps, alors que les traitements spécifiques, les médicaments et les appareils sont graduellement retirés.
• Il faut revoir et modifier fréquemment les objectifs des soins quand on prend en charge des problèmes médicaux concomitants. La nécessité de prendre certain médicaments ainsi que leur mode et leur fréquence d’administration doivent être évalués régulièrement.
This article is eligible for mainpro-m1 credits. To earn credits, go to www.cfp.ca and click on the Mainpro link.
La traduction en français de cet article se trouve à www.cfp.ca dans la table des matières du numéro de mars 2011 à la page e89.
This article is eligible for Mainpro-M1 credits. To earn credits, go to www.cfp.ca and click on the Mainpro link.
Palliative Care Files
treatment or withdraw medication might occur all at once as a single and complete change in direction, or they might take place over time, with specific treatments, medications, and devices (eg, implantable cardioverter defibrillator, continuous positive airway pressure) being gradually withdrawn.2,3
Little guidance exists to help physicians consistently manage chronic comorbidities during this period of change. Frequent review and amendments to goals of care are necessary when managing medical comorbidities. The need for certain medications, as well as their route and time of administration, should be evaluated regularly. We must always be looking at what is best for the patient.4
One month later, you see Margaret on a house visit. It is too difficult for her to visit your office now. It has been more than 2 months since her diagnosis, and she spends most of her days in bed. She has a poor appetite, with occasional nausea but no vomiting. Her husband com- ments on the number of pills she has to take and how it has become a chore. She denies any pain and complains of shortness of breath with slight exertion but not at rest.
On physical assessment, she has lost 25 lb (she now weighs 105 lb) and her mucous membranes are dry. Air
entry is decreased in her right lung. Respiration is at a rate of 26 breaths/min and slightly laboured while talk- ing. She needs assistance to get up out of bed and with her activities of daily living. There has been a substantial functional decline in Margaret in a very short time, with her palliative performance scale version 2 score at 40%.5 New medications are initiated to help manage her symp- toms of dyspnea and nausea. You recognize that the time has come to initiate discussion about the need for a num- ber of her medications at this stage of her disease.
Period of change
A patient facing a palliative diagnosis and prognosis, and coming to grips with a limited life expectancy of weeks to a few months, deserves to have discussions on goals of care introduced. It is best to have these discussions with patients and their families. As illness progresses, a catabolic state develops as fat, carbohydrate, and pro- tein metabolism is altered. This catabolic state coupled with the release of various cytokines adds to the triad of anorexia, weight loss, and fatigue. Consequently weight loss, possible cachexia, and dehydration arise. During end-of-life care, it is common for new medications to be added for symptoms such as nausea,
306
Canadian Family Physician•Le Médecin de famille canadien|
Vol 57: March • Mars 2011Palliative Care Files
dyspnea, and pain, to name a few. There is a great poten- tial for polypharmacy and its consequent adverse effects if these medications are added to existing medications for comorbidities.6
You and a home care nurse visit Margaret and her hus- band to talk about medication withdrawal. (Table 16,7 summarizes factors to consider when withdrawing medications.) During this period of change, commu- nication, support, and reassurance are essential; it is important to discuss and redefine the goals of care and treatments. Based on the evidence, Margaret and her
husband can make informed decisions. Given the evi- dence (number need to treat and time until benefit) and her considerable physical and functional decline (pallia- tive performance scale score at 40%), it seems reasonable to discontinue atorvastatin and alendronate.8,9 After dis- cussing evidence on primary and secondary prevention with antihypertensives, she agrees to stop using ramipril and hydrochlorothiazide. She continues to take metopro- lol as long as she is able, as it might prevent morbidity (angina and tachycardia) given her history of coronary artery disease and atrial fibrillation.10
After reviewing her anticoagulation therapy, you decide it is important to consider some form of anticoagula- tion with her high risk of venous thromboembolism and resulting morbidity. Margaret is informed of the increased risk of adverse consequences of warfarin such as bleeding complications, especially in her state of nutritional com- promise and with the interference of competing medica- tions. She and her husband are frustrated by the frequency of phlebotomy, as her international normalized ratio is often out of therapeutic range. She is informed of the risks of stopping her warfarin and given the option of no further anticoagulation versus injections of low-molecular-weight heparin, which do not require monitoring. The evidence is weak but does support low-molecular-weight hep- arin in palliative care even in advanced disease; however, it is clearly a decision based on benefit versus burden.11-14 Margaret decides to forgo any further treatment with anti- coagulants, and you support her in this decision.
The UKPDS15 (UK Prospective Diabetes Study) has formed the cornerstone of current guidelines in the man- agement of type II diabetes. Extrapolating these guide- lines and applying them to a population with a very limited life expectancy might not be practical. Looking at number needed to treat and time to effect with con- ventional diabetic treatments suggests we do not need aggressive treatment or tight glucose control. A glucose level of about 15 mmol/L or an undesirable symptom resulting from hyperglycemia might be cause to consider initiating oral hypoglycemics. Intensive treatments with insulin increase the risk of hypoglycemia, not to mention the discomfort and inconvenience of insulin injections.16
Discussions are initiated regarding Margaret’s diabetic medication. She is anorexic and has had no hypoglyce- mic episodes, but there is concern about the risk if she continues taking her diabetic medication. After discuss- ing the options, she agrees with stopping her metformin.
She agrees to occasional glucose testing at her and her husband’s discretion based on symptoms.
Two weeks later the palliative home support nurse receives a call from Margaret’s husband. Margaret’s condition has deteriorated substantially. She is unable to take any oral medications and only has sips of liquid.
table 1. Factors to consider when withdrawing medications
FACTOrS ExPLAnATiOn
Dialogue There needs to be frequent dialogue on goals of care, as goals might change Framework for
care We need to create a framework for care to aid in clinical decision making in the pharmacologic management of comorbid medical conditions
Metabolism of drugs and the pathophysiology of death
We need to consider the net effect of a drug such as a BP medication as death approaches, given the altered nutritional and hydration state of a patient and the risks of polypharmacy. The net effect of the medication might be greater (ie, marked drops in BP resulting in substantial morbidity)
Measure of benefit vs burden, or the NNT
In the palliative care setting, the NNT for a comorbidity will increase as the prognosis or life expectancy decreases and therefore the benefit decreases
Time until benefit
Is life expectancy long enough to benefit from a particular medication? Medications for primary or secondary prevention often have a time to benefit of years before the desired outcome is achieved. Stopping or not initiating medication might be in the best interest of a patient
Prognosis or
natural history We need to consider prognosis or natural history of the medical comorbidities and the life-threatening illness
Medical
intervention What is the intention of medical
intervention? Primary, secondary, or tertiary prevention?
Polypharmacy and consequent adverse effects
We must have an understanding of the potential for polypharmacy and the consequent adverse effects
Other factors We need to consider the emotional, psychological, and cultural effects of withdrawing drugs
BP—blood pressure, NNT—number needed to treat.
Data from Stevenson et al6 and Holmes et al.7
From this point all of her oral medications are stopped.
The focus is on her palliative symptoms and great atten- tion is given to good pain and symptom management, as well as emotional support for both her and her hus- band. She dies peacefully 4 days later.17
Dr O’Brien is a family physician, Medical Director of Palliative Care Services at Horizon Health Network in Saint John, NB, and Lecturer in the Department of Family Medicine at Dalhousie University in Saint John.
competing interests None declared references
1. National Cancer Institute [website]. Lung cancer. Bethesda, MD: National Cancer Institute; 2011. Available from: www.cancer.gov/cancertopics/
types/lung/. Accessed 2011 Jan 29.
2. Faber-Langendoen K, Lanken PN. Dying patients in the intensive care unit:
forgoing treatment, maintaining care. Ann Inter Med 2000;133(11):886-93.
3. Wiegand DL, Kalowes PG. Withdrawal of cardiac medications and devices.
AACN Adv Crit Care 2007;18(4):415-25.
4. Urie J, Fielding H, McArthur D, Kinnear M, Hudson S, Fallon M. Palliative care.
Pharm J 2000;265(7119):603-14.
5. Victoria Hospice Society [website]. Palliative performance scale (PPSv2) version 2.
Victoria, BC: Victoria Hospice Society; 2006. Available from: www.victoriahospice.
org/sites/default/files/imce/PPS%20ENGLISH.pdf. Accessed 2011 Feb 18.
6. Stevenson J, Abernethy AP, Miller C, Currow DC. Managing comorbidities in patients at the end of life. BMJ 2004;329(7471):909-12.
7. Holmes HM, Hayley DC, Alexander GC, Sachs GA. Reconsidering medication appropriateness for patients late in life. Arch Intern Med 2006;166(6):605-9.
8. Do statins have a role in primary prevention? Ther Lett 2003;48:1-2.
9. Ridker PM, MacFadyen JG, Fonseca FA, Genest J, Gotto AM, Kastelein JJ, et al. Number needed to treat with rosuvastatin to prevent first cardiovascular events and death among men and women with low low-density lipoprotein cholesterol and elevated high-sensitivity C-reactive protein: justification for
the use of statins in prevention: an intervention trial evaluating rosuvastatin (JUPITER). Circ Cardiovasc Qual Outcomes 2009;2(6):616-23. Epub 2009 Sep 22.
10. Medscape Today [website]. Treatment of hypertension to prevent stroke: num- ber needed to treat. New York, NY: WebMD; 2011. Available from: www.
medscape.com/viewarticle/407726_3. Accessed 2011 Jan 29.
11. Spiess JL. Can I stop the warfarin? A review of the risks and benefits of dis- continuing anticoagulation. J Palliat Med 2009;12(1):83-7.
12. Soto-Cárdenas MJ, Pelayo-García G, Rodríguez-Camacho A, Segura- Fernández E, Mogollo-Galván A, Giron-Gonzalez JA. Venous thromboembo- lism in patients with advanced cancer under palliative care: additional risk factors, primary/secondary prophylaxis and complications observed under normal clinical practice. Palliat Med 2008;22(8):965-8. Epub 2008 Oct 24.
13. Noble S, Johnson M. Finding the evidence for thromboprophylaxis in pallia- tive care: first let us agree on the question. Palliat Med 2010;24(4):359-61.
14. Noble SI, Finlay IG. Is long-term low-molecular-weight heparin acceptable to palliative care patients in the treatment of cancer related venous thrombo- embolism? A qualitative study. Palliat Med 2005;19(3):197-201.
15. UK Prospective Diabetes Study (UKPDS) Group. Intensive blood-glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes (UKPDS 33). Lancet 1998;352(9131):837-53.
16. Vandenhaute V. Palliative care and type II diabetes: a need for new guide- lines? Am J Hosp Palliat Care 2010;27(7):444-5. Epub 2010 Apr 13.
17. Adam J. ABC of palliative care. The last 48 hours. BMJ 1997;315(7122):1600-3.
Palliative Care Files is a quarterly series in Canadian Family Physician written by members of the Palliative Care Committee of the College of Family Physicians of Canada. The series explores common situations experienced by family physicians doing palliative care as part of their primary care practice. Please send any ideas for future articles to palliative_care@cfpc.ca.
