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Fast Facts

• Fast Fact and Concept #008; Morphine and Hastened Death
• Fast Fact and Concept #010; Tube Feed or Not Tube Feed?
• Fast Fact and Concept #005; Treatment of Nausea and Vomiting
• Fast Fact and Concept #011; Delivering Bad News Part II - Talking
to Patients and Precepting Trainees
• Fast Fact and Concept #75: Methadone for the Treatment of Pain

Fast Fact and Concept #008; Morphine and Hastened Death

2nd Edition
Author(s): Charles F. von Gunten, MD
Question : What is the distinction between the use of morphine at the end of life to control symptoms and euthanasia/assisted suicide?
Case Scenario: An 83 year old former industrial worker has been hospitalized because of severe pain. He has pancreatic cancer with metastases to liver and lung. He has severe abdominal pain.
Main Teaching Points :

Many physicians inaccurately believe that morphine has an unusually or unacceptably high risk of an adverse event that may cause death, particularly when the patient is frail or close to the end of his or her life. In fact, morphine-related toxicity will be evident in sequential development of drowsiness, confusion and loss of consciousness before his respiratory drive is significantly compromised.
Many physicians inappropriately call this risk of a potentially adverse event, a double effect, when it is in fact a secondary, unintended consequence. The principle of double effect refers to the ethical construct where a physician uses a treatment, or gives medication, for an ethical intended effect where the potential outcome is good (eg, relief of a symptom), knowing that there will certainly bean undesired secondary effect (such as death). An example might be the separation of Siamese twins knowing that one twin will die so that the other will live. Although this principle of “double effect” is commonly cited with morphine, in fact, it does not apply, as the secondary adverse consequences are unlikely.
When offering a therapy, it is the intent in offering a treatment that dictates whether it is ethical medical practice:
- if the intent in offering a treatment is desirable or helpful to the patient and the potential outcome good (such as relief of pain), but a potentially adverse secondary effect is undesired and the potential outcome bad (such as death), then the treatment is consideredethical
- If the intent is not desirable or will harm the patient and the potential outcome bad, the treatment is consideredunethical
All medical treatments have both intended effects and the risk of unintended, potentially adverse, secondary consequences, including death. Some examples are TPN, chemotherapy, surgery, amiodarone, etc.
Assisted suicide and Euthanasia are not examples of “double effect.” The intent in offering the treatment is to end the patient’s life.
If the intent in morphine in the scenario is to relieve pain and not to cause death, and accepted dosing guidelines are followed:
- the treatment is considered ethical
- the risk of a potentially dangerous adverse secondary effects is minimal
- the risk of respiratory depression is vastly over-estimated.

Reference: Emanuel LL, von Gunten CF, Ferris FD. (1999) The Education for Physicians on End-of-Life Care (EPEC) curriculum. American Medical Association, Chicago.

Fast Facts are edited by David E. Weissman, MD; Palliative Care Center, Medical College of Wisconsin. For comments/questions write to: dweissma@mail.mcw.edu. The complete set of Fast Facts are available at EPERC: www.eperc.mcw.edu

Copyright/Referencing Information : Users are free to download and distribute Fast Facts for educational purposes only. Citation for referencing: von Gunten CF. Morphine and Hastened Death . Fast Fact and Concept #8; 2nd Edition, August 2005. End-of-Life Physician Education Resource Center www.eperc.mcw.edu.

Disclaimer: Fast Facts provide educational information, this information is not medical advice. Health care providers should exercise their own independent clinical judgment. Some Fast Fact information cites the use of a product in dosage, for an indication, or in a manner other than that recommended in the product labeling. Accordingly, the official prescribing information should be consulted before any such product is use

Creation Date: 2/2000; 2nd Edition, August 2005.

Fast Fact and Concept #010; Tube Feed or Not Tube Feed?

2nd Edition
Author(s): James Hallenbeck MD
Tube feeding is frequently used in chronically ill and dying patients. The evidence for much of this use is weak at best. The Fast Fact reviews data on the use of tube feeding..

For prevention of aspiration pneumonia

Numerous observational studies have demonstrated a high incidence of aspiration pneumonia in those who have been tube fed. Reduction in the chance of pneumonia has been suggested for non-bed-ridden post-stroke patients in one prospective, non-randomized study. For bedridden post-stroke patients, no reduction was observed.
Three retrospective cohort studies comparing patients with and without tube feeding demonstrated no advantage to tube feeding for this purpose.
Swallowing studies, such as videofluoroscopy, lack both sensitivity and specificity in predicting who will develop aspiration pneumonia. Croghan’s (1994) study of 22 patients undergoing videofluoroscopy demonstrated a sensitivity of 65% and specificity of 67% in predicting who would develop aspiration pneumonia within one year. In this study no reduction in the incidence of pneumonia was demonstrated in those tube fed.
Swallowing studies may be helpful in providing guidance regarding swallowing techniques and optimal food consistencies for populations amenable to instruction. See Fast Fact #128 for discussion of the role of swallowing studies.

For life prolongation via caloric support

Data is strongest for patients with reversible illness in a catabolic state (such as acute sepsis).
Data is weakest in advanced cancer. No improvement in survival has been found (see exceptions noted below).
Individual patients may have weight stabilization or gain with tube feeding. However, when cohorts of patients have been studied in non-randomized retrospective or prospective studies, no survival advantage between tube fed and hand fed cohorts has been demonstrated.
Tube feeding may be life-prolonging in select circumstances:
- Patients with good functional status and proximal GI obstruction due to cancer
- Patients receiving chemotherapy/XRT involving the proximal GI tract.
- Selected HIV patients
- Patients with Amyotrophic Lateral Sclerosis

For enhancing quality of life

Where true hunger and thirst exist, quality of life may be enhanced (such as in very proximal GI obstruction).
Mostactively dying patients (see Fast Fact #3) do not experience hunger or thirst (although dry mouth is a common problem, there is no relation to hydration status and the symptom of dry mouth, see Fast Fact #133).
A recent literature review using palliative care and enteral nutrition as search terms found no studies demonstrating improved quality of life through tube feeding. (Limited to a few observational studies.)
Tube feeding may adversely affect quality of life if patients are denied the pleasure of eating.

Summary

Although commonly used, current data does not provide much support for the use of artificial enteral nutrition in advanced dementia, or in patients on a dying trajectory from a chronic illness. A recommendation to use, or not use, tube feeding should be made only after first establishing the overall Goals of Care(see Fast Fact #16). Recommendations for how to discuss the issue tube feeding with patients/families can be found in Fast Fact #84.

References

Loeb MB, Becker M, Eady A, Walker-Dilks C. Interventions to prevent aspiration pneumonia in older adults: a systematic review. J Am Geriatr Soc. 2003;51(7):1018-1022.
Meier DE, Ahronheim JC, Morris J, Baskin-Lyons S, Morrison RS. High Short-term Mortality in Hospitalized Patients With Advanced Dementia: Lack of Benefit of Tube Feeding. Arch Intern Med. 2001;161(4):594-599.
Nakajoh, K., T. Nakagawa, et al. (2000). "Relation between incidence of pneumonia and protective reflexes in post- stroke patients with oral or tube feeding." J Intern Med247(1): 39-42.
Finucane T, Christmas C, Travis K. Tube feeding in patients with advanced dementia. JAMA. 1999;282:1365-1369.
Finucane T, Bynum J. Use of tube feeding to prevent aspiration pneumonia. Lancet. 1996;348:1421-1424.
Croghan J, Burke E, Caplan S, Denman S. Pilot study of 12-month outcomes of nursing home patients with aspiration on videofluroscopy. Dysphagia. 1994;9:141-146.

Copyright/Referencing Information: Users are free to download and distribute Fast Facts for educational purposes only. Citation for referencing: Hallenbeck, J. Fast Facts and Concepts #11 To feed or not to feed. August 2005, 2nd Edition. End-of-Life Physician Education Resource Center www.eperc.mcw.edu.

Disclaimer : Fast Facts provide educational information, this information is not medical advice. Health care providers should exercise their own independent clinical judgment. Some Fast Fact information cites the use of a product in dosage, for an indication, or in a manner other than that recommended in the product labeling. Accordingly, the official prescribing information should be consulted before any such product is used.

Creation Date: 4/2000; August 2005, 2nd Edition

Fast Fact and Concept #005; Treatment of Nausea and Vomiting

2nd Edition
Author(s): James Hallenbeck, MD
By understanding the pathophysiology of nausea and targeting antiemetics to specific receptors, therapy can be optimized and side effects minimized. An easy way to remember the causes of vomiting is the VOMIT acronym. In the table below receptors involved in different types of nausea are highlighted using this acronym. Blockade of these receptors allows rational, focused therapy.

Cause - Vestibular

Receptors Involved - Cholinergic, Histaminic
Drug Class Useful - Anticholinergic, Antihistaminic
Drug Examples - Scopolamine patch, Promethazine

Cause - Obstruction of Bowel caused by constipation

Receptors Involved - Cholinergic, Histaminic, 5HT3
Drug Class Useful - Stimulate myenteric plexus
Drug Examples - Senna products

Cause - DysMotility of upper gut

Receptors Involved - Cholinergic, Histaminic, 5HT3
Drug Class Useful Prokinetics stimulate 5HT4 receptors
Drug Examples - Metoclopramide

Cause - Infection, Inflammation

Receptors Involved - Cholinergic, Histaminic, 5HT3, Neurokinin 1
Drug Class Useful - Anticholinergic, Antihistaminic, 5HT3 antagonists,
Neurokinin 1 antagonist
Drug Examples - Promethazine

Cause - Toxins stimulating the CTZ in the brain such as Opioids

Receptors Involved - Dopamine 2, 5HT3
Drug Class Useful - Antidopaminergic, 5HT3 Antagonist
Drug Examples - Prochlorperazine, Haloperidol, Ondansetron

Note: Phenergan and Compazine are very different drugs. Phenergan is useful for vertigo and gastroenteritis due to infections and inflammation. Compazine is preferred for opioid related nausea.

Note: There is no good evidence supporting the use of lorazepam as a sole agent for nausea. Sedated patients are more prone to aspiration.

References

Glare P et al. Systemic review of the efficacy of antiemetics in the treatment of nausea in patients with far-advanced cancer.
Hallenbeck J. Palliative Care Perspectives. New York: Oxford University Press; 2003. 75-86. cancer. Support Care Cancer 2004; 12:432-440

Copyright/Referencing Information: Users are free to download and distribute Fast Facts for educational purposes only. Citation for referencing: Hallenbeck, J. Fast Fact and Concepts #5: Causes of Nausea and Vomiting (V.O.M.I.T.). August 2005, 2nd Edition. End-of-Life Physician Education Resource Center www.eperc.mcw.edu.

Disclaimer: Fast Facts provide educational information, this information is not medical advice. Health care providers should exercise their own independent clinical judgment. Some Fast Fact information cites the use of a product in dosage, for an indication, or in a manner other than that recommended in the product labeling. Accordingly, the official prescribing information should be consulted before any such product is used.

Creation Date: 2/2000; August 2005, 2nd Edition.

Fast Fact and Concept #011; Delivering Bad News Part II - Talking to Patients and Precepting Trainees

2nd Edition

Author(s): Bruce Ambuel, PhD and David E. Weissman, MD

Case Scenario: You are caring for a previously healthy 52 y/o man with one-month of abdominal pain and weight loss. On exam he had a 2 cm hard left supraclavicular lymph node. A CAT scan showed a focal mass with ulceration in the body of the stomach and numerous densities in the liver compatible with liver metastases. The radiologist feels that the findings are consistent with metastatic stomach cancer. How do you discuss these test results with the patient?

Steps in Delivering Bad News

Determine what the patient & family knows; make no assumptions. Examples: What is your understanding of your present condition? Or What have the doctors told you?
Before presenting bad news, consider providing a brief overview of the patient’s course so that every one has a common source of information.
Speak slowly, deliberately and clearly. Provide information in small chunks. Check reception frequently
Give fair warning: I am afraid I have some bad news then pause for a moment.
Present bad news in a succinct and direct manner. Be prepared to repeat information and present additional information in response to patient and family needs.
Sit quietly. Allow the news to sink in. Wait for the patient to respond.
Listen carefully and acknowledge patient’s and family’s emotions, for example by reflecting both the meaning and emotion of their response.
Normalize and validate emotional responses: feeling numb, angry, sad, and fearful.
Give an early opportunity for questions, comments
Present information at the patient’s or family’s pace; do not overwhelm with detail. The discussion is like pealing an onion. Provide an initial overview. Assess understanding. Answer questions. Provide the next level of detail or repeat more general information depending upon the patient’s and family’s needs.
Assess thoughts of self-harm
Agree on a specific follow-up plan (I will return later today, write down any questions.). Make sure this plan meets the patient’s needs. Involve other team members in follow-up.

Precepting Points

Residents often feel strong emotions when they have to give bad news to a patient. This emotional response can be heightened by various factors—a young patient, an unexpected diagnosis, a patient with whom the physician has a long-standing relationship, etc. As a preceptor, you will want to support the resident. Key teaching points:

Residents may not spontaneously discuss their own emotional reaction with a preceptor, therefore you will want to introduce this topic.
Physicians often have strong emotional reactions when a patient encounters bad news. This is normal and OK.
Three methods for coping with these feelings: Identify your feelings (anger, sadness, fear, guilt); Talk with a colleague; Keep a personal journal.

Resources

Buckman R. How to break bad news: A guide for health care professionals. Johns Hopkins University Press, 1992.
Faulkner A. Breaking bad news--a flow diagram. Palliative Medicine 1994:8;145-151.
Iverson, VK. Pocket protocols—Notifying survivors about sudden, unexpected deaths. Galen Press, Inc., Tuscon, Arizona, 1999.
Ptacek, JT, Eberhardt, TL. Breaking bad news: A review of the literature. JAMA, 157:323, 1996.
Sim, I. How to give bad news. http://www-med.stanford.edu/school/DGIM/Teaching/Modules/badnews.html
Quill TE. Bad news: delivery, dialogue and dilemmas. Arch Intern Med 1991; 151:463-468.
Girgis A and Sanson-Fischer RW. Breaking bad news: consensus guidelines for medical practitioners. J Clin Onc 1995;13:2449-2456.
Von Gunten CF, Ferris FD and Emanuel LL. Ensuring competency in end-of-life care: Communication and Relational Skills. JAMA 2000; 284:3051-3057.

Copyright/Referencing Information : Users are free to download and distribute Fast Facts for educational purposes only. Citation for referencing. Fast Facts and Concepts #11 Ambuel B and Weissman DE. Delivering Bad News; Part 2. September 2005. 2 nd Edition End-of-Life Palliative Education Resource Center www.eperc.mcw.edu.

Creation Date: 4/2000

FAST FACT AND CONCEPT #75: Methadone for the Treatment of Pain

2nd Edition

Author: G Gazelle and PG Fine

Methadone, a potent opioid agonist, has many characteristics that make it useful for the treatment of pain when continuous opioid analgesia is indicated. Although available for decades, its use has gained renewed interest due to its low cost and potential activity in neuropathic pain syndromes. Unlike morphine, methadone is a racemic mix; one stereoisomer acts as a NMDA receptor antagonist, the other is a mu-agonist opioid. The NMDA mechanism plays an important role in the prevention of opioid tolerance, potentiation of opioid effects, and efficacy for neuropathic pain syndromes, although this latter impression is largely anecdotal.

Any clinician with a Schedule II DEA license can prescribe methadone for pain; a special license is only required to prescribe methadone for the treatment of addiction. In some jurisdictions, it is necessary to apply the words “for pain” on the prescription. Methadone is highly lipophilic with rapid GI absorption and onset of action. It has a large initial volume of distribution with slow tissue release. Oral bioavailability is high, ~ 80%. Unlike morphine there are no active metabolites; biotransformation to an active drug is not required. The major route of metabolism is hepatic with significant fecal excretion; renal excretion can be enhanced by urine acidification (pH <6.0). Unlike morphine, no dose adjustment is needed in patients with renal failure since there are no active metabolites. Methadone is available in tablet, liquid and injectable forms; oral preparations can be used rectally. Parenteral routes include IV bolus dosing or continuous infusion.

Unlike morphine, hydromorphone or oxycodone, methadone has an extended terminal half-life, up to 190 hours. This half-life does not match the observed duration of analgesia (6-12 hours) after steady state is reached. This long half-life can lead to increased risk for sedation and respiratory depression, especially in the elderly or with rapid dose adjustments. Rapid titration guidelines for other opioids do not apply to methadone. Given recent reports that high-dose methadone may be associated with development of Torsades, depending upon life expectancy and goals of care, EKG monitoring may be appropriate when changes in dosage are made. An important property of methadone is that its apparent potency, compared to other opioids, varies with the patient’s current exposure to other opioids. Suggested Dosing Guide for Opioid Tolerant Patients 1

Daily oral morphine dose equivalents	Conversion ratio of oral morphine to oral methadone
<100 mg	3:1 (i.e., 3 mg morphine:1 mg methadone)
101-300 mg	5:1
301-600 mg	10:1
601-800 mg	12:1
801-1000 mg	15:1
>1001 mg	20:1

Due to incomplete cross-tolerance, it is recommended that the initial dose is 50-75% of the equianalgesic dose.

Summary

Compared to morphine, methadone is inexpensive, may provide improved analgesia in neuropathic pain and will provide a longer duration of action. Dosing intervals at the start of treatment are q 4-6 hours, and may be increased over time to q 6-12 hours.
Methadone is not indicated in poorly controlled pain where rapid dose adjustments are needed; do not increase oral methadone more frequently than every 4 days.
Dose conversion to/from other opioids and methadone is complex; consultation with pain management specialists familiar with methadone use is recommended.
Patient and family education is essential as they may misinterpret prescription of methadone to mean that their physician believes that they already are an addict.

References

Ayonrinde OT, Bridge DT. The rediscovery of methadone for cancer pain management. Med J Austral. 2000;173:536-40.
Bruera E, Sweeney C. Methadone use in cancer patients with pain: A review. J Pall Med. 2002:5(1):127-38.
Iribarne C, Dreano Y, Bardou LG, et al. Interaction of methadone with substrates of human hepatic cytochrome P450 3A4. Toxicology 1997; 117:13-23
Krantz MJ, Lewkowiez L, Hays H, et al. Torsade de Pointes associated with very-high-dose methadone. Ann Intern Med. 2002;137:501-4.
Morley JS, Makin MK. The use of methadone in cancer pain poorly responsive to other opioids. Pain Rev 1998;5:51-8.
Rowbotham MC. The debate over opioids and neuropathic pain. In, Kalso E, McQuay HJ, Wiesenfeld-Hallin Z, eds. Opioid Sensitivity of Chronic Noncancer Pain, Progress in Pain Research and Management, Vol. 14, 1999, Seattle, IASP Press, pp 307-317.

Fast Facts are edited by David E. Weissman, MD; Palliative Care Center, Medical College of Wisconsin. For comments/questions, write to: dweissma@mcw.edu. The complete set of Fast Facts is available at EPERC: http://ww.eperc.mcw.edu

Copyright and Referencing Information: Users are free to download and distribute Fast Facts for educational purposes only. Citation for referencing: Gazelle G and Fine PG. Fast Facts and Concepts #75: Methadone for the treatment of pain, 2 nd Edition. July 2006. End-of-Life Physician Education Resource Center: http://www.eperc.mcw.edu.

Disclaimer: Fast Facts provide educational information. This information is not medical advice. Health care providers should exercise their own independent clinical judgment. Some Fast Fact information cites the use of a product in dosage, for an indication, or in a manner other than that recommended in the product labeling. Accordingly, the official prescribing information should be consulted before any such product is used.

Creation Date: 9/2002