#221Treatment of Pain in Patients Taking Buprenorphine for Opioid Addiction

FAST FACTS AND CONCEPTS #221

Treatment of Pain in Patients Taking Buprenorphine for OPIOID ADDICTION

Julie W Childers MD and Robert Arnold MD

Background This Fast Fact discusses treating pain in patients using buprenorphine for opioid addiction. Buprenorphine is a mixed opioid agonist/antagonist, available in the United States in the sublingual form as ‘Subutex,’ and formulated with naloxone as ‘Suboxone.’ It is approved for treatment of opioid addiction in the US; such use is restricted to qualified physicians who have received training and a waiver to practice medication-assisted opioid addiction therapy. Over the last seven years, over 10,000 physicians have been approved to use buprenorphine, with 2,103,000 prescriptions filled in 2007. Given this, clinicians are likely to encounter patients on buprenorphine therapy who also require treatment for pain. Note: buprenorphine is also used as an analgesic, particularly in Europe, where a transdermal system is available. Currently it is uncommonly used in the US as an analgesic. Naloxone has minimal sublingual bioavailability and is included only to prevent abuse by intravenous injection; in this Fast Fact ‘buprenorphine’ refers to both sublingual products.

Pharmacology Buprenorphine binds to mu-opioid receptors tightly but with low intrinsic activity, providing some analgesic effects but effectively preventing other opioids from binding. This ‘blocks’ the analgesic and euphoric effects of other opioids, leading to its effectiveness in opioid addiction therapy. Buprenorphine’s effect at the mu-opioid receptor lasts 24 to 60 hours, and can lengthen even further with increasing doses. The duration of sublingual buprenorphine’s analgesic effects is shorter than its occupation of the receptor – between 6 and 12 hours. When patients on buprenorphine therapy for addiction are in acute pain, the continued interaction of buprenorphine with opioid receptors can limit other opioids’ analgesic effectiveness.

Pain Management Strategies While there are no clinical studies addressing how to treat pain in patients taking buprenorphine, the strategies below are derived from expert opinion, animal studies, federal guidelines, and international experience treating breakthrough pain in patients using transdermal buprenorphine (not available in the US). As with all patients with pain, non-pharmacologic therapies and non-opioid analgesics should be used when safe and likely to work. The following strategies should be chosen and implemented in close collaboration with the physician treating the patient’s opioid addiction.

• If acute pain is anticipated, such as for an elective surgical procedure, adjuvant analgesics and interventional procedures such as nerve blocks should be provided as available.
• For patients with moderate to severe pain who are expected to require opioid analgesic therapy for the short term, federal guidelines recommend holding the buprenorphine and starting short acting opioid agonists. While the buprenorphine’s effects diminish (20-60 hours), the patient may require higher opioid doses to compete with the presence of buprenorphine on mu-opioid receptors. The patient should be monitored carefully in the initial period to titrate the opioid agonist dose downward as its effect becomes greater. Before restarting buprenorphine, the patient should be opioid-free for 12-24 hours to avoid precipitating withdrawal. This process should be overseen by an approved buprenorphine provider.
• For patients with mild to moderate acute pain, consider treating the pain with buprenorphine alone. The total daily dose of buprenorphine can be increased (to a maximum of 32 mg sublingual/day); it should be given in divided doses every 6-8 hours.
• Another option is to continue buprenorphine and use short-acting opioid agonists at high enough doses to overcome buprenorphine’s partial agonism. Opioids that have a higher intrinsic activity at the mu-opioid receptor, including morphine, fentanyl, or hydromorphone, are all options, while opioids with less efficacy such as hydrocodone or codeine should be avoided.
• In a patient who is expected to have an ongoing need for pain management, consider replacing buprenorphine with methadone therapy for opioid addiction. For analgesia, additional methadone or other ‘full’ mu-opioid receptor agonists can then be added without problems related to use of a partial opioid agonist.
• Patients who have life-limiting illnesses that are expected to cause significant pain are not good candidates for buprenorphine therapy for addiction. A collaborative approach, including patient preference and discussion with both addiction and pain or palliative care specialists, will best identify a therapeutic plan to achieve adequate pain relief and maintain recovery from addiction.

Author Affiliations: University of Pittsburgh Medical Center, Pittsburgh, PA.

References

1. Alford DP, et al. Acute pain management for patients receiving maintenance methadone or buprenorphine therapy. Ann Intern Med. 2006; 144:127-134.
2. Center for Substance Abuse Treatment. Clinical Guidelines for the Use of Buprenorphine in the Treatment of Opioid Addiction. Treatment Improvement Protocol (TIP) Series 40. DHHS Publication No. (SMA) 04-3939. Rockville, MD: Substance Abuse and Mental Health Services Administration, 2004. Available at http://buprenorphine.samhsa.gov/Bup_Guidelines.pdf. Accessed June 25, 2009.
3. Heit HA, Gourlay DL. Buprenorphine: new tricks with an old molecule for pain management. Clin J Pain. 2008; 24:93-97.
4. Helm S, et al. Opioid antagonists, partial agonists, and agonists/antagonists: the role of office-based detoxification. Pain Physician. 2008; 11:225-235.
5. Johnson RE, Fudula PJ, Payne R. Buprenorphine: considerations for pain management. J Pain Symptom Manage. 2005; 29(3):297-326.
6. Kögel B, Christoph T, Strassburger W, Friderichs E. Interaction of mu-opioid receptor agonists and antagonists with the analgesic effect of buprenorphine in mice. Eur J Pain. 2005; 9(5):599-611.
7. Mark, TL, Kassed CA, Vandivort-Warren R, et al. Alcohol and opioid dependence medications: prescription trends, overall and by physician specialty. Drug Alcohol Depend. 2009; 99:345-349.
8. Mercadante S, Villari P, Ferrera P, et al. Safety and effectiveness of intravenous morphine for episodic breakthrough pain in patients receiving transdermal buprenorphine. J Pain Symptom Manage. 2006; 32(2):175-9.
9. Schumacher MA, Basbaum AI, Way WL. Opioid analgesics and antagonists. In: Katzung BG, ed. Basic and clinical pharmacology. New York, NY: McGraw-Hill; 2007.

Fast Facts and Concepts are edited by Drew A. Rosielle MD, Palliative Care Center, Medical College of Wisconsin. For more information write to: drosiell@mcw.edu. More information, as well as the complete set of Fast Facts, are available at EPERC: www.eperc.mcw.edu. Readers can comment on this publication at the Fast Facts and Concepts Discussion Blog (http://epercfastfacts.blogspot.com).

Copyright/Referencing Information: Users are free to download and distribute Fast Facts for educational purposes only. Childers JW, Arnold R. Treatment of Pain in Patients Taking Buprenorphine for Opioid Addiction. Fast Facts and Concepts. November 2009; 221. Available at: http://www.eperc.mcw.edu/fastfact/ff_221.htm.

Disclaimer: Fast Facts and Concepts provide educational information. This information is not medical advice. Health care providers should exercise their own independent clinical judgment. Some Fast Facts cite the use of a product in a 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.

#220 Hypodermoclysis

FAST FACTS AND CONCEPTS #220

HYPODERMOCLYSIS

Arif H Kamal MD and Eduardo Bruera MD

Background This Fast Fact discusses subcutaneous fluid infusions, also known as hypodermoclysis (HDC). The use of parenteral hydration in dying patients is controversial and is discussed in Fast Fact #133. While this Fast Fact discusses subcutaneous fluid infusions for purposes of hydration, similar techniques can also be used to deliver medications (see Fast Fact #28).

Historical and Current Practice Hypodermoclysis was a widely accepted route for parenteral hydration in the 1940s and 1950s before falling out of favor after several reports of adverse reactions, likely related to the use of hypertonic and electrolyte-free solutions. Due to its ease of use, and subsequent research demonstrating its safety and efficacy, HDC has become more widely used. In the US, HDC is mostly used in geriatric and palliative care settings, although it is used more widely elsewhere in the world.

HDC vs. Intravenous Hydration Decisions for parenteral hydration in dying patients are complex and individual decision making is paramount. When parenteral hydration is indicated, clinicians are generally faced with a decision to use HDC or intravenous (IV) hydration (see Fast Fact #134).

• Advantages of HDC over IV: Starting and maintaining a subcutaneous infusion catheter is relatively pain-free. It can be done by trained patients or family caregivers, preventing the need for frequent skilled nursing visits or trips to medical centers to maintain a working IV. HDC provides greater potential sites for needle placement (arm, back, abdomen, thighs), and equipment costs are generally lower than with IVs. Subcutaneous catheters can be easily disconnected from IV tubing and re-used later, allowing a patient to receive intermittent fluid treatments. Portable infusion devices are not needed with HDC. HDC infusions may also cause less agitation in patients with dementia versus IV (1).
• Disadvantages: HDC is limited by a continuous infusion rate of 1-2 ml/min or 1.5-3 L/day (2). This is adequate for most clinical situations, and additional catheters can be added if needed. Bolus infusions (up to 500 ml/hour) are possible with HDC, but often require hyaluronidase (see below). Both HDC and IV infusions have similar rates of local adverse events (e.g. erythema, cellulitis) and lifespan of infusion site (3). HDC can be technically difficult in patients with substantial peripheral edema, as well as in cachectic patients with little subcutaneous tissue. Patients and families may have pre-conceived attitudes about greater benefits with IV routes even while acknowledging increased burden (4).

Technique

• Equipment needed: Small butterfly needle (usually 22 gauge) or angiocatheter, skin preparation (alcohol or iodine), sterile occlusive dressing, solution bag (saline or saline-dextrose combination), tubing with drip chamber. The use of electrolyte free solutions (e.g. 5% dextrose) is discouraged due to third-spacing risks which can cause tissue sloughing or rarely circulatory collapse.
• Procedure: After cleaning the local site, insert the needle bevel up into the subcutaneous tissue. Attach to fluid and tubing and cover with occlusive dressing. Select an infusion fluid and set drip rate or fluid bolus. Normal saline (NS) is typically used although half-normal saline or 2/3 D5W in 1/3 NS have been used in clinical practice. Drip rates can be set to 20-125 ml/hour with gravity (no pump required) or 1-2 ml/minute. Some patients may prefer drips set to gravity 24 hours per day at a low rate (e.g. 50 ml/hour), overnight hydration (e.g. 100 ml/hour), or intermittent fluid boluses (e.g. 500 ml). The volume of infusion needed to keep acceptable levels of hydration in many palliative care patients is lower than healthy patients and postulated to be ~1 L/day (5). No evidence exists for the frequency of site change. Some change only when there are symptoms or needle displacement while others choose a fixed time (e.g. every 3 or 7 days) or fluid volume (e.g. every 1.5 L) Teflon cannulas, although expensive, can be used for a week and are helpful for patients who have trouble maintaining a catheter site (6). Local anesthetic creams may be helpful during catheter placement to reduce discomfort, especially in children.
• Recombinant human hyaluronidase: RHH is an enzyme that temporarily lyses the subcutaneous interstitial space to promote diffusion of fluid. It can be used for site discomfort or if a faster rate of absorption is desired. Previous preparations were of bovine origin and were associated with local allergic reactions, anaphylaxis, and pain, making its role controversial. RHH has shown no human allergenicity (7). Recent studies have investigated RHH versus placebo in a randomized trial with gravity-driven infusion. The RHH group showed higher obtainable fluid rates, decreased discomfort, and similar local reactions. Doses of 150 U to 750 U given as steady push prior to the infusion can yield fluid rates of 380 to 520 ml/hour (8).

Cautions Uncommon local reactions include edema, local pain, or erythema. Interventions include slowing the rate, changing the site, or using RHH. Rare complications include cellulitis and vascular puncture. Systemic complications such as pulmonary edema can occur with all types of parenteral hydration.

References

1. O'Keeffe ST, Lavan JN. Subcutaneous fluids in elderly hospital patients with cognitive impairment. Gerontology. 1996; 42(1):36-39.
2. Berger EY. Nutrition by hypodermoclysis. J Am Geriatr Soc. 1984; 32(3):199-203.
3. Slesak G, Schnurle JW, Kinzel E, Jakob J, Dietz PK. Comparison of subcutaneous and intravenous rehydration in geriatric patients: a randomized trial. J Am Geriatr Soc. 2003; 51(2):155-160.
4. Mercadante S, Ferrera P, Girelli D, Casuccio A. Patients' and relatives' perceptions about intravenous and subcutaneous hydration. J Pain Symptom Manage. 2005; 30(4):354-358.
5. Dalal S, Bruera E. Dehydration in cancer patients: to treat or not to treat. J Support Oncol. 2004; 2(6):467-479, 483.
6. Macmillan K, Bruera E, Kuehn N, Selmser P, Macmillan A. A prospective comparison study between a butterfly needle and a Teflon cannula for subcutaneous narcotic administration. J Pain Symptom Manage. 1994; 9(2):82-84.
7. Yocum RC, Kennard D, Heiner LS. Assessment and implication of the allergic sensitivity to a single dose of recombinant human hyaluronidase injection: a double-blind, placebo-controlled clinical trial. J Infus Nurs. 2007; 30(5):293-299.
8. Thomas JR, Yocum RC, Haller MF, von Gunten CF. Assessing the role of human recombinant hyaluronidase in gravity-driven subcutaneous hydration: the INFUSE-LR study. J Palliat Med. 2007; 10(6):1312-1320.

Author Affiliations: Mayo Clinic, Rochester, MN (AK) and University of Texas M.D. Anderson Cancer Center, Houston, TX (EB).

Fast Facts and Concepts are edited by Drew A. Rosielle MD, Palliative Care Center, Medical College of Wisconsin. For more information write to: drosiell@mcw.edu. More information, as well as the complete set of Fast Facts, are available at EPERC: www.eperc.mcw.edu. Readers can comment on this publication at the Fast Facts and Concepts Discussion Blog (http://epercfastfacts.blogspot.com).

Copyright/Referencing Information: Users are free to download and distribute Fast Facts for educational purposes only. Kamal AH, Bruera E. Hypodermoclysis. Fast Facts and Concepts. October 2009; 220. Available at: http://www.eperc.mcw.edu/fastfact/ff_220.htm.

Disclaimer: Fast Facts and Concepts provide educational information. This information is not medical advice. Health care providers should exercise their own independent clinical judgment. Some Fast Facts cite the use of a product in a 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.

#219 Responding to Requests for Non-disclosure

FAST FACTS AND CONCEPTS #219

RESPONDING TO REQUESTS FOR NON-DISCLOSURE OF MEDICAL INFORMATION

Elizabeth Chaitin DHCE and Drew A Rosielle MD

Background What do you do when a family member asks you not to tell your patient important medical information such as a diagnosis or prognosis? Requests for non-disclosure can represent a loving family’s efforts to protect a patient from emotional harm, an inaccurate assessment by the family about a patient’s preferences or emotional resilience, or an accurate reflection of how the patient would prefer to make decisions. This Fast Fact will introduce readers to a practical approach to these clinical dilemmas.

The Problem Contemporary medical ethics and professional standards dictate that patients have the right to choose the medical care that best allows them to meet their life goals. To make such choices requires they be fully informed of their condition, prognosis, and reasonable treatment options (see Fast Facts #164, 165). One needs to differentiate the right to such information from the duty to hear the information, however. Patients have different preferences for medical decision-making, ranging from individualistic, to paternalistic (doing whatever the physician recommends), to communal (sharing, or deferring, important medical decisions to family members or religious/community leaders). Truly respecting patient autonomy requires clinicians to identify and respect patient wishes to share or defer decision-making, including a patient’s preference to not be informed of key medical information.

Prevention Negotiate with the patient before the results of testing arrive as to how much information they would like and who they would like to have present for information sharing. Are you the kind of person who wants to know the results of the test or would you rather I talk to your children?

Managing Requests for Non-Disclosure (adapted from Hallenbeck and Arnold, 2007):

· Stay Calm. These situations can be confusing and emotional for clinicians. The calmer you remain the more information you will gain from the family as to why they do not want their loved one to be informed of the bad news. Demonstrating frustration or implying that the request is inappropriate can break trust and derail your efforts to resolve the situation.

· Try to understand the family’s viewpoint. They know the patient best and can provide insight into the cause of the request. Politely ask questions to understand the nature of the request. Can you tell me more about why you feel this way? How does your family typically handle difficult information? How are important decisions made by your family? Ask about how the patient has responded in the past to bad news and if they have made specific statements to others about what they want to know. Is the family more worried more about how the information is given rather than the information itself (e.g. given to the patient when alone, use of ‘death’ or ‘dying,’ the disclosure of specific prognostic time-frames)?

· Clarify what the patient already knows. Politely ask questions to understand what the family believes the patient already knows. Does the family think the patient already knows or strongly suspects what is going on and would rather not talk further about it, or is the patient completely in the dark? Have other clinicians already told or implied to the patient what is going on? How did the patient respond to that? Is the patient talking with the family about their concerns? A patient’s reluctance to talk with family members may represent an attempt to protect them.

· Respond empathically. A family’s request to not tell their loved ones usually comes from a kind and loving place; they are often frightened for themselves and the patient. Responding empathically (see Fast Fact #29) allows them to recognize that you care about them. It may allow them to see your ability to give information to their loved one in a compassionate way.

· State your views openly, but as your own views. Disclose any discomfort you have with the family’s request; explain your professional obligation to ensure the patient is able to make informed decisions in the manner they prefer. Disclose this specifically in the context of you wanting what is best for the patient, including respecting how she or he would like to hear information.

· Be willing to brainstorm possible solutions. Rigidly informing the family that you must tell the patient breaks trust and is inaccurate. There is no ‘one-size-fits-all’ solution to these scenarios. Often, there are solutions neither of you have thought about that will meet everyone’s goals. In other cases, the family may not have thought about the implications of the request (e.g. giving Mom chemotherapy but not telling her she has cancer).

· Negotiate a solution. Recommend to the family that you, in their presence, share with the patient a limited amount of information, and then specifically ask the patient if they would like to hear more. Tell the family what you plan on saying, i.e. – You came to the hospital because you were not eating well and became dehydrated. We have been trying to figure out what is going on. Some people want to know everything about their medical condition, others prefer the doctors talk with family members about what is happening and the best way to help a patient. What would you prefer? Contract with the family that they, and you, will respect the patient’s decision.

References

1. Bok S. Lying: Moral Choice in Public and Private Life. New York, NY: Vintage Books; 1989.
2. Hallenbeck J, Arnold R. A request for nondisclosure: don’t tell mother. J Clin Oncol. 2007; 25(31):5030-34.
3. Lagarde SM, Franssen SJ, van Werven JR, et al. Patient preferences for the disclosure of prognosis after esophagectomy for cancer with curative intent. Ann Surg Oncol. 2008; 15(11):3289-3298.

Author Affiliations: University of Pittsburgh Medical Center, Pittsburgh, PA (EC); Medical College of Wisconsin, Milwaukee, WI (DAR).

Fast Facts and Concepts are edited by Drew A. Rosielle MD, Palliative Care Center, Medical College of Wisconsin. For more information write to: drosiell@mcw.edu. More information, as well as the complete set of Fast Facts, are available at EPERC: www.eperc.mcw.edu. Readers can comment on this publication at the Fast Facts and Concepts Discussion Blog (http://epercfastfacts.blogspot.com).

#218: Managing Wound Odor

FAST FACTS AND CONCEPTS #218

MANAGING WOUND ODOR

Bansari Patel APN and Deon Cox-Hayley DO

Background Foul-smelling non-healing wounds are common in patients nearing the end-of-life, whether from pressure ulcers, vascular disease, or tumors. Strong wound odors can lead to social and physical isolation, altered patient body image and self-worth, and can challenge caregivers. This Fast Fact will discuss a practical approach to ameliorating wound odors. See also Fast Facts #40 and #41 (pressure ulcers), #46 (malignant wounds), and #185 (topical opioids).

Pathophysiology Most wound odors are thought to be due the metabolic processes of anaerobic bacteria, which colonize devitalized tissue. Deeper infection (e.g. cellulitis, necrotizing infections) are not necessary for significant odor generation.

Management While it should be addressed, treatment of the underlying cause of the wound is often limited in patients with advanced illnesses. In all circumstances, attempts at ameliorating wound odor are important – whether by treating the cause of the odor or hiding the odor.

· Addressing the cause of the odor:

o Remove the wound bed contaminants (e.g. debride the wound of necrotic tissue).

o Control infection. There are several approaches, all aimed at controlling anaerobic growth.

· Topical Metronidazole is available as a commercially produced gel. Metronidazole gel is applied directly to the wound once or twice daily. Studies have shown decreases in wound odor in 2-3 days, and application is usually continued for up to 2 weeks. Courses can be repeated if needed. In one study, 63% of patients had complete eradication of odor after a course of metronidazole gel, with the remainder reporting improvements. Costs can range from dollars for compounded gels to ~$45-$75 for 45 gm of commercial gel. Metronidazole tablets can also be broken and the powder contents sprinkled into the wound. Applying dressings soaked in a mixture of normal saline and metronidazole has also been reported as helpful for controlling odor.

· Systemic Metronidazole can be used if there is evidence of deep tissue infection causing foul odor. 500 mg 3 or 4 times daily IV or orally is used, instead of or in addition to topical metronidazole. Systemic side effects such as nausea and diarrhea can occur.

· Topical Silver Sulfadiazine has been shown to be helpful in controlling odors of superficial wounds.

· Cadexomer Iodine is an antimicrobial agent containing slow release iodine and has been shown to decrease bacterial counts and odor from venous ulcers. Ointment, powder and impregnated bandage forms are available. Cadexomer iodine has the added benefit of absorbing exudate and can be particularly helpful when exudate absorption and odor control are both needed. It can cause a burning sensation upon application.

· Yogurt or buttermilk, applied for 15 minutes after a wound is cleaned, have been reported to control malignant wound odor, though studies are limited. They are thought to control bacterial proliferation by lowering a wound’s pH.

· Honey can be bacteriocidal, and has been increasingly studied for wound healing. There is some evidence that it decreases odor.

· Hiding the odor:

o Aromatics: Scented candles, air freshener sprays, peppermint and other essential oils, coffee beans or grounds, and cider vinegar in a pan are all used to hide odors.

o Adsorbents: Charcoal adsorbs aromatic molecules. A basket of charcoal (briquettes) can be placed discreetly in a patient’s room. Various commercially available charcoal dressings are also available, although expensive. These dressings are applied over the primary dressing and may be re-used as long as they remain dry. Baking soda can be applied between dressing layers to help absorb odor. Cat litter can also be used similarly to charcoal briquettes.

Support and Education There can be great psychosocial distress associated with malodorous wounds: embarrassment, shame, and isolation. In addition to wound care specialists, psychological and spiritual support services can be important in helping patients and families cope with a chronic wound. Educate the patient and caregivers about the management of chronic wounds, and commit to controlling odor as much as possible. Health care providers should be trained to avoid demonstrating distress at odors in front of or in hearing distance of patients or families.

References

1) Alvarez O, Meehan M, Ennis W, et al. Chronic Wounds: Palliative Management for the Frail Population Part III. Wounds. 2002; 14(8S):13-18.

2) Bates-Jensen B, Seaman S, Early L. Skin Disorders: Tumor Necrosis, Fistulas, and Stomas. In: Ferrel B, Coyle N, eds. Textbook of Palliative Nursing. New York, NY: Oxford University Press; 2006: pp330-333.

3) Cooper RA, Jenkins L. A comparison between medical grade honey and table honeys in relation to antimicrobial efficacy. Wounds. 2009; Issue 2 February. Available at: http://www.woundsresearch.com/content/a-comparison-between-medical-grade-honey-and-table-honeys-relation-antimicrobial-efficacy. Accessed May 12, 2009.

4) Fonder M, Lazurus G, Cowan D, et al. Treating the chronic wound: A practical approach to the care of nonhealing wounds and wound care dressings. J Am Acad Dermatol. 2008; 58:185-206.

5) Kalinski C, Schneph M, Laboy D, et al. Effectiveness of a Topical Formulation Containing Metronidazole for Wound Odor and Exudate Control. Wounds. 2005; 17(4):84-90.

6) McDonald A, Lesage P. Palliative Management of Pressure Ulcers and Malignant Wounds in Patients with Advanced Illness. J Palliat Med. 2006; 9(2):285-295.

7) Sussman C, Jensen-Bates B. Wound Care: A Collaborative Practice Manuel. Philadelphia, PA: Lippincott Williams & Wilkins; 2006.

Author Affiliations: University of Chicago, Chicago, Illinois.

Fast Facts and Concepts are edited by Drew A. Rosielle MD, Palliative Care Center, Medical College of Wisconsin. For more information write to: drosiell@mcw.edu. More information, as well as 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. Patel B, Cox-Hayley D. Managing Wound Odor. Fast Facts and Concepts. August 2009; 218. Available at: http://www.eperc.mcw.edu/fastfact/ff_218.htm.

Disclaimer: Fast Facts and Concepts provide educational information. This information is not medical advice. Health care providers should exercise their own independent clinical judgment. Some Fast Facts cite the use of a product in a 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.

#217 Restless Leg Syndrome

FAST FACTS AND CONCEPTS #217

RESTLESS LEG SYNDROME

Jennifer Johnson MD, PhD and Robert Arnold MD

Background Restless Leg Syndrome (RLS) is a neurologic disorder characterized by unpleasant sensations in the legs causing an uncontrollable urge to move when at rest in an effort to relieve those feelings. Between 2-15% of the population have RLS, with a peak incidence between 40 and 60 years of age and a 1:2 male:female ratio. It occurs more frequently in end-stage renal disease patients on chronic hemodialysis (up to 60%, depending on the series), and in patients with Parkinson’s disease (up to 20%) than in the general public. RLS disrupts sleep, can lead to excessive daytime sleepiness, depression, and a decreased quality of life. This Fast Fact will review its evaluation and management.

Causes The etiology of primary RLS is unknown although it is thought to be a genetic disorder involving either central or peripheral dopaminergic pathways. Common secondary causes of RLS are polyneuropathies; diabetes mellitus; rheumatologic diseases such as rheumatoid arthritis, Sjogren’s syndrome, and fibromyalgia; renal failure; pregnancy; iron deficiency; and hypo- or hyperthyroidism. Drugs including nicotine, caffeine, alcohol, 2^nd generation antidepressants such as SSRIs and SNRIs, neuroleptic agents, dopamine-blocking antiemetics such as metoclopramide, and sedating antihistamines are all known to worsen RLS symptoms.

Symptoms and Diagnosis The International RLS Study Group and the National Institutes of Health (NIH) criteria for diagnosis include: (1) an urge to move the legs, (2) temporary relief with movement, (3) onset or worsening of symptoms with rest or inactivity, and (4) worsening or onset of symptoms in the evening or night (3). Patients describe symptoms of trouble falling asleep, trouble getting back to sleep, "a funny feeling in the legs," or a "creepy or crawly feeling in the legs." Patients or their bed partners may also report ‘periodic limb movements of sleep’: stereotyped, repetitive flexion movements (‘jerking’) of the legs and occasionally arms, exacerbated when patients lie down for prolonged periods. RLS is a clinical diagnosis for which there is not a confirmatory diagnostic test. It should be differentiated from akathisia, a constant and generalized feeling of motor restlessness not associated with leg discomfort or rest. It can be differentiated from peripheral neuropathies, lumbosacral radiculopathy, and ordinary leg cramps by its circadian rhythm, relief with movement, and the prominence of pain symptoms in non-RLS syndromes.

Treatment Address any treatable secondary causes of RLS (e.g. with iron repletion or levothyroxine) and work with patients to avoid drugs and medications known to aggravate RLS. Distraction activities such as playing video games or crossword puzzles can decrease symptoms during wakeful periods. Drug treatment is recommended for patients who have not improved despite conservative interventions or who have persistent, distressing symptoms. Given the paucity of studies comparing different drugs, experts recommend the following (14):

· Dopamine agonists: The most frequently used drugs are the dopamine agonists, pramipexole and ropinirole. Both have been determined to be effective in industry-funded, double-blind, placebo-controlled studies (7, 8). Doses as low as 0.125 mg of pramipexole at bedtime or 0.25 mg of ropinirole are effective in improving sleep and decreasing discomfort in mild-to-moderate cases. Doses of greater than 0.75 mg/day of pramipexole or 4 mg/day of ropinirole are of unproven benefit. Side effects are usually mild, transient, and limited to nausea, lightheadedness, and fatigue. Both drugs cost roughly $100 (US) a month at the starting dose. While there are small series showing the effectiveness of levodopa/carbidopa, experts have recommended it only be used for intermittent RLS because of worries that levodopa may cause augmentation, rebound, or recurrence of symptoms. Finally, cabergoline, a dopamine agonist with a long half life may be useful for patients who experience rebound symptoms with shorter acting agents, although it is not FDA approved for this purpose.

· Other agents: There are small studies indicating that benzodiazepines (9), opioids (10), and select anticonvulsants such as gabapentin and carbamazepine (11, 12, 13) are effective in RLS. Expert opinion, however, generally recommends these drugs as second line agents due to the paucity of data supporting their use relative to dopamine agonists, side effects, and risk of abuse.

References

1. Phillips B, Young T, Finn L, et al. Epidemiology of restless legs symptoms in adults. Arch Intern Med. 2000; 160:2137-2141.
2. Zucconi M, Ferini-Strambi L. Epidemiology and clinical findings of restless legs syndrome. Sleep Med. 2004; 5:293-299.
3. Allen RP, Picchietti D, Hening WA, et al. Restless legs syndrome: diagnostic criteria, special considerations, and epidemiology. A report from the restless legs syndrome diagnosis and epidemiology workshop at the National Institutes of Health. Sleep Med. 2003; 4:101-119.
4. Connor JR, Wang XS, Patton SM, et al. Decreased transferrin receptor expression by neuromelanin cells in restless legs syndrome. Neurology. 2004; 62:1563-1567.
5. Pittock SJ, Parrett T, Adler CH, et al. Neuropathology of primary restless leg syndrome: absence of specific tau- and alpha-synuclein pathology. Mov Disord. 2004; 19:695-699.
6. Silber MH, Richardson JW. Multiple blood donations associated with iron deficiency in patients with restless legs syndrome. Mayo Clin Proc. 2003; 78:52-54.
7. Montplaisir J, Nicolas A, Denesle R, Gomez-Mancilla B. Restless legs syndrome improved by pramipexole: a double-blind randomized trial. Neurology.1999; 52:938-943.
8. Adler CH, Hauser RA, Sethi K, et al. Ropinirole for restless legs syndrome: a placebo-controlled crossover trial. Neurology. 2004; 62:1405-1407.
9. Peled R, Lavie P. Double-blind evaluation of clonazepam on periodic leg movements in sleep. J Neurol Neurosurg Psychiatry. 1987; 50:1679-1681.
10. Ondo WG. Methadone for refractory restless legs syndrome. Mov Disord. 2005; 20:345-348.
11. Telstad W, Sorensen O, Larsen S, et al. Treatment of the restless legs syndrome with carbamazepine: a double blind study. BMJ. 1984; 288:444-446.
12. Garcia-Borreguero D, Larrosa O, de la Llave Y, et al. Treatment of restless legs syndrome with gabapentin: a double-blind, cross-over study. Neurology. 2002; 59:1573-1579.
13. Eisensehr I, Ehrenberg BL, Rogge Solti S, Noachtar S. Treatment of idiopathic restless legs syndrome (RLS) with slow-release valproic acid compared with slow-release levodopa/benserazide. J Neurol. 2004; 251:579-583.
14. Silber MH, Ehrenberg BL, Allen RP, et al. An algorithm for the management of restless legs syndrome. Mayo Clin Proc. 2004; 79(7):916-22.

Author Affiliations: University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania.

#216 Asking About Cultural Beliefs in Palliative Care

FAST FACTS AND CONCEPTS #216

Asking about cultural beliefs in palliative care

Hillary Lum MD, PhD and Robert Arnold MD

Background Patients’ cultural backgrounds profoundly influence their preferences and needs regarding discussing bad news, decision-making, and the dying experience. This Fast Fact offers a framework for taking a ‘cultural history’ to better understand a patient’s and family’s needs. See also these related Fast Facts: #17 (illness experience), #19 (spiritual history), #26 (explanatory model), #183/184 (conflict resolution).

C – Communication. Identify the patient’s preferences regarding how and to whom medical information is shared. Some people want to know everything about their medical condition, and others do not. How much would you like to know? For those who request that the physician discuss their condition with family members: Would you like me to speak with them alone, or would you like to be present? Identify main contacts to give information to about the patient’s condition. Carefully explore with families requests to hide information from a patient (see references 4 and 5) – a future Fast Fact will address this topic in more detail.

U – Unique cultural values. Use respectful, curious, and open-ended questions about a patient’s cultural heritage to identify their values. Is there anything that would be helpful for me to know about how you and your family view serious illness? Are there cultural beliefs, practices, or preferences that affect you during times of significant illness? If the patient is open to discussing death: What concerns do you have about dying? Are there things that are important to you or your family that I should know about?

L – Locus of decision-making. For some patients medical decision-making is communally driven rather than individualistic. Multiple family members or a community elder or leader may need to be involved, often without prior official documentation because it is assumed or understood from the patient’s perspective. Do you prefer to make medical decisions about tests and treatments yourself, or would you prefer that others in your family or community make them for you?

T – Translators. Language barriers are extremely challenging, especially during times of severe illness. Utilize medical interpreters frequently and effectively. Refer to Fast Fact #154 for a detailed discussion on using interpreters in palliative care.

U – Understanding the patient and learning as a provider. Reassess what is being heard, understood, and agreed upon frequently, from both the patient’s and clinician’s standpoint. Specifically confirm the patient’s understanding or agreement (beyond nodding or “yes” responses). This is particularly important if a medical translator is involved as miscommunication is common even when using trained medical interpreters – see reference (6). Can you tell me – in your own words – what you have heard from me and what’s most important to you about what I’ve said?

R – Ritualized practices and restrictions. Determine if there are specific customs the patient desires to be followed. These must be communicated to other health care providers, especially in the hospital setting. It may be necessary to advocate for the patient and negotiate with healthcare facility administrators to find an agreeable way to honor a patient’s wishes. Are there specific practices that you would like to have in the hospital or at home? Are there aspects of medical care that you wish to forgo or have withheld because of your cultural beliefs? Is anything discouraged or forbidden? If the patient is approaching death, and willing to discuss it: Are there specific practices that are important to you at the time of death or afterwards that we should know about?

E – Environment at home. Given that a majority of hospice care happens in the patient’s home environment, respectfully explore whether there are any needs that can be met by the health care system, and how open the patient, family or community is to receiving care at home. Recognize that patients may be hesitant to voice needs, or resistant to accepting help from outside the community. Even if a trusting, collaborative relationship has developed between a patient/family and clinicians in the hospital, this may not immediately translate into the home setting. With the patient’s permission, expectations about cultural-specific aspects of a patient’s care should be explicitly communicated to care providers outside the hospital.

References

1. Searight HR, Gafford J. Cultural Diversity at the End of Life: Issues and Guidelines for Family Physicians. Am Fam Phys. 2005; 71 (3)
2. Crawley LM, et al. Strategies for Culturally Effective End-of-Life Care. Ann Internal Med. 2002; 136:673-679.
3. Maugans TA. The SPIRITual History. Arch Fam Med. 1997; 5:11-16.4. Arnold R. Palliative Care Case of the Month: The Family Says Not to Tell. University of Pittsburgh Institute to Enhance Palliative Care. May 2006. Available at: http://www.dgim.pitt.edu/SPC/cases/May 06.doc.

5. Hallenbeck J, Arnold R. A request for non-disclosure: don’t tell mother. J Clin Oncol. 2007; 25(31):5030-4.
6. Pham K, et al. Alterations During Medical Interpretation of ICU Family Conferences That Interfere With or Enhance Communication. Chest. 2008; 134(1):109-116.

Author Affiliations: University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania.