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The contents of this blog contain topics relevant to end of life care written by our own hospice clinical pharmacists. Continue to check this site regularly for the newest post or subscribe to the RSS feed below.
Jessica Horsley, PharmD

Intranasal Medication Administration: Suitable Drugs and Devices

Compared to intravenous (IV) and other invasive routes of administration, intranasal (IN) administration of medications provides several benefits with regard to safety and efficacy. This route of administration is needleless, requires no sterile technique and is pain-free and well tolerated by patients. The transmucosal drug absorption offered by this route offers a rapid onset of action, with dosing and bioavailability similar to IV dosing.

Variability in intranasal drug absorption can be attributed to both drug and patient-related factors. Drug formulations should be concentrated and potent and of a volume of less than 1mL (preferably less than 0.2mL if possible). Physicochemical drug properties are of importance, as optimal absorption is dependent on the molecular weight and hydro- or lipophilicity of the drug. Lipophilic medications with a molecular weight of less than 300 Da are most suitable for IN administration. The patient’s transepithelial passage proves to be another variable affecting drug absorption. Abnormal nasal blood flow, rhinosinusitis, radiation to the head/neck, diseases affecting mucociliary clearance like cystic fibrosis, and cigarette smoking may all affect mucosal health, and therefore IN drug absorption. Drug interactions for IN administration are considered relative and include phenylephrine and oxymetazoline.

With regard to IN administration, most nursing professionals and even patients are familiar with nose drops or aerosol sprays like sodium chloride nasal spray or fluticasone. For those medications without a commercial nasal dosage form available, options for administration in the past have included compounding into drops/spray, or using a syringe and cotton ball. These methods may prove problematic due to immediate swallowing, rapid clearance, and posterior delivery of medication. A new option, drug atomization, now exists to address these failures in IN drug delivery. An atomized spray delivers small particles to the nasal mucosa rapidly and without regard to patient positioning. Three commercial devices exist for IN drug atomization: Mucosal Atomization Device, Accuspray Nasal Spray and Kurve Controlled Particle Dispersion. Although considered off-label use, the therapeutic uses of IN-administered drugs include seizures, hypoglycemia, opioid overdose, epistaxis and anesthesia. Suitable medications for IN administration applicable to the hospice population include fentanyl, benzodiazepines, ketamine, naloxone and lidocaine.1

2016 06 29 12 57 45

For information regarding nasal atomization products:


BD Accuspray SCF

Kurve CPD



1 Jen, C. No IV access, get MAD! Powerpoint presentation at: the American Society for Health-System Pharmacists Midyear Clinical Meeting; Dec 7-11 2014; Anaheim, CA.

2 Wolfe TR, Braude DA. Intranasal medication delivery for children: a brief review and update. Pediatrics. 2010;126(3):532-7.

3 Gallagher EJ. Nasogastric tubes: hard to swallow. Ann Emerg Med. 2004;44:138-41.

4 Pandey RK, Bahetwar SK, Saksena AK, Chandra G. A comparative evaluation of drops versus atomized administration of intranasal ketamine for the procedural sedation of young uncooperative pediatric dental patients: A prospective crossover trial. J Clin Pediatr Dent. 2011;36:79–84.

5 Tsze DS, Steele DW, Machan JT, Akhlaghi F, and Linakis JG. Intranasal ketamine for procedural sedation in pediatric laceration repair: a preliminary report. Pediatr Emerg Care. 2012 Aug;28(8):767-770.

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Delta Campus Pharmacy Student

Use of Nebulized Morphine for the Management of Dyspnea

Dyspnea, or shortness of breath, is a very common complaint in hospice and palliative care. Up to 70% of end stage cancer or COPD patients experience dyspnea.1 Opioids, such as morphine, have been used to relieve the uncomfortable sensation associated with dyspnea. Oral and parenteral morphine are the most well studied routes of administration for this indication. Unfortunately, systemic absorption of opioids can cause adverse events that may be considered unbearable in the hospice population such as nausea, vomiting, drowsiness, constipation, and respiratory depression. Oral administration of morphine takes 15-30 minutes to take effect and lasts about four hours.2,3 While parenteral administration of morphine takes 6-10 minutes to take effect and also last about four hours. Inhaled opioids have a faster onset of action than the oral route and considered less invasive than the parenteral route.2

The use of nebulized opioids can be considered an appealing option compared to the oral and parenteral routes of administration. However, nebulized opioids are not routinely recommended. This is because there is conflicting data as to their benefit. There are no large-scale studies testing the efficacy of nebulized opioids, and smaller studies show conflicting evidence. Some studies show that nebulized opioids are less effective compared to oral or parenteral administration while others show that nebulized morphine is equally efficacious to subcutaneous morphine.1,4 Some patients are noted to prefer nebulized morphine over other routes of administration.4

A systematic review of 18 clinical trials that evaluated all routes of opioids in the management of dyspnea found a statistically significant benefit with the oral and parenteral routes of administration but found the nebulized route of administration to be no more effective than nebulized saline. However, the authors of this review did note that there might have been insufficient data with the nebulized route of administration to make this claim.8 Another review of 9 clinical trials looking at efficacy of nebulized morphine in the management of dyspnea found that 3 of the trials had positive results, but the rest failed to show improvement after treatment. The authors note that the small number of subjects, variety of disease states, and different outcome measures limited the interpretation of the results.9 Based upon these varying results, the use of nebulized opioids for the management of dyspnea are not routinely recommended. If you are going to consider a trial of a nebulized opioid, then it is recommended to use an injectable vial and not the oral morphine concentrate. A review of the literature will find no place where the oral concentrate has been evaluated and one article that directly states that the oral elixir should not be used.10 There is some belief that the sugar-free formulation of the oral morphine solution can be used via nebulizer, however, there is not literature to support this. It is of note that all current oral morphine solutions are sugar free and that the sugar containing oral morphine solutions are no longer on the market.7 There is some concern if the injectable vial needs to be preservative free for use via nebulizer. This concern comes from the fact the preservatives can induce bronchospasm in some patients. This is a rare but sometimes serious side effect. The preservatives of most concern are sulfites and edetate disodium (EDTA), found in both oral and parenteral preparations of morphine.5,6 It is not necessary to use preservative-free morphine, but caution should be used in patients susceptible to bronchospasms. If you are not using a preservative free product, then it is recommended to monitor your patient during the first administration of the nebulized opioid for this side effect. Typical starting dose for nebulized morphine is 2.5-10 mg; this can be titrated up to 30 mg per dose. Alternatives to morphine include hydromorphone 0.25- mg or fentanyl 25 mcg.1 Doses can be repeated every 4 hours as needed.3 Morphine for injection should be diluted to 2 mL volume with normal saline solution, if needed.1

Submitted by: Shawn Millsop, PharmD Candidate 2016 at Duquesne University School of Pharmacy and Lorin Yolch, PharmD, CGP, FASCP, Director of Professional Education at Delta Care Rx


1 Ferraresi V. Inhaled opioids for the treatment of dyspnea. Am J Health-Syst Pharm. 2005; 62: 319-320.

2 Bausewein C, Simon ST. Inhaled nebulized and intranasal opioids for the relief of breathlessness. Curr Opin Support Palliat Care. 2014; 8: 208-212.

3 Sarhill N, Walsh D, Khawarm E, Tropiano P, Stahley MK. Nebulized hydromorphone for dyspnea in hospice care of advanced cancer. Am J Hosp Palliat Care. December 2000; 17(6): 389-391.

4 Bruera E, Sala R, Spruyt, et al. Nebulized Versus Subcutaneous Morphine for Patients with Cancer Dyspnea: A Preliminary Study. J Pain Symptom Manage. June 2005: 29(6): 613-618.

5 Excipients in the label and package leaflet of medicinal products for human use. European Commission. http://www.ema.europa.eu/docs/en_GB/document_library/Scientific_guideline/2009/09/WC500003412.pdf Published July 2003. Accessed June 2, 2015.

6 Beasley R, Fishwick D, Miles JF, Hendeles L. Preservatives in nebulizer solutions: risk without benefit. Pharmacotherapy. January-February 1998; 18(1): 130-139.

7 Gold Standard, Inc. Morphine. Clinical Pharmacology [database online]. Available at: http://www.clinicalpharmacology.com. Accessed June 25, 2015.

8 Jennings AL, Davies AN, Higgins JP, Gibbs JSR, Boardley KE. A Sytematic Review of the use of Opioids in the management of dyspnoea. Thorax. 2002;57:939-44.

 9 Brown SJ, Eichner SF, Jones JR. Nebulized Morphine for Relief of Dyspnea Due to Chronic Lung Disease. The Annals of Pharmacotherapy. June 2005;29:1088-92.

10 Ahmedzai S, Davis C. Nebulised drugs in palliative care. Thorax. 1997;52(Suppl 2):S75-77.

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Shane Donnelly, PharmD

Prescription Drug Misuse, Dependence, and Abuse in the Elderly

Older adults are often left out of the discussion when it comes to prescription drug misuse, dependence, and abuse. Prescription drug abuse is an epidemic in this country, and it’s not just confined to the younger patient population. It is estimated that 11% of elderly patients abuse prescription medication.1

The elderly consume roughly one quarter of the prescriptions sold in the United States.1 Elderly patients often have chronic pain, anxiety, or insomnia that requires the use of potentially addictive medication. Additionally, elderly patients may not be adequately treated with their current therapies. These risk factors, along with social isolation, depression, and limited functionality, make the geriatric population particularly at risk for substance misuse and abuse.

Providing safe and effective care for elderly patients requires that signs of prescription misuse, dependence, and abuse are recognized quickly. The medications that are often abused can lead to events such as falls and accidents that require these patients to be admitted to inpatient units or nursing homes. To effectively manage prescription medication misuse and abuse in this population, the definition of substance misuse, dependence, tolerance, and abuse should be addressed.

Misuse- Prescription medication misuse is the improper taking of medication by the patient. It is most commonly by accident, but can also be intentional. Assess your patient’s ability to take medication correctly. It may be necessary to provide pharmaceutical education to your patient.  Examples include.2

• Taking medication differently than directed on the label due to poor eyesight or reading ability

• Doubling up on doses

• Borrowing medication from friends or family members

• Acquiring medication online to treat self-diagnosed conditions

Physical dependence and Tolerance- Physical dependence evolves from the continued regular use of a substance that results in withdrawal symptoms upon discontinuation. Tolerance to medication occurs when patients need higher doses of medication to achieve adequate symptomatic relief. Patients with physical dependence and tolerance may display drug-seeking behavior that can be misconstrued as psychological dependence (addiction).2 Assess the patient’s current condition and medication profile. The patient’s therapy may be inadequate due to tolerance or lack of efficacy. Communicate concerns with the patient’s physician. The patient may then cease to engage in drug-seeking behavior.

Psychological dependence (addiction)- Psychological dependence is a state that demonstrates loss of control and/or compulsive drug-seeking behavior.3 These patients engage in medication use despite the potential for adverse consequences. These patients need professional help to overcome both physical and psychological dependence. At this point, it is important to understand that these patients are potentially putting themselves and others in immediate danger.

In hospice, it is rare for a patient to become psychologically dependent on medication. It is important to be aware of any signs of substance abuse among family members or caregivers. Recognizing signs of caregiver abuse is important to protect patients and provide the best possible care for the end-of-life stage. It’s important to listen your patient’s concerns regarding their medication and to assess the root cause of medication discrepancies.


1 Culbertson JW, Ziska, M. Prescription drug misuse/abuse in the elderly. Geriatrics. 2008; 63(9): 22-31.

2 Agins, A. Prescription drug abuse: from bad to worse. CEdrugstorenews.com March/April 2012. Retrieved July 5, 2012 at: http://www.cedrugstorenews.com/userapp//lessons/lesson_view_ui.cfm?lessonuid=401-000-12-201-H01.

3 American Psychiatric Association. Diagnostic and Statistical Methods of Mental Disorders (Fourth Edition, Text Revision). Washington, DC: American Psychiatric Association. 2000;199-273

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Jessica Horsley, PharmD

Music Therapy in Hospice and Palliative Care

Music Therapy (MT) is an established health profession in which music is used within a therapeutic relationship to address physical, emotional, cognitive, and social needs of individuals. It is the clinical and evidence-based use of music interventions to accomplish individualized goals within a therapeutic relationship by a credentialed professional who has completed an approved music therapy program. Although note-worthy and possibly soothing in nature, activities like bedside and lobby performances, background music and providing media players/headphones are NOT considered clinical music therapy.

Board Certified Music Therapists (MT-BC) work in a variety of settings including schools, nursing facilities, hospitals, and hospices. After assessing the strengths and needs of each client, the qualified music therapist provides the indicated treatment including creating, singing, moving to, and/or listening to music. Through musical involvement in the therapeutic context, clients' abilities are strengthened and transferred to other areas of their lives. Music therapy also provides avenues for communication that can be helpful to those who find it difficult to express themselves in words.1

MT has shown benefit for many conditions relevant to the care of a hospice patient. In dementia, including Alzheimer’s, MT can reduce behaviors like agitation,2 improve speech and attention,3 even make shower/bath times easier for patients and caregivers.4 Incorporating MT into Parkinson’s therapy improves gait,5, 6 speech and mood.7 Of particular interest to the hospice population, MT can treat anxiety,8 dyspnea9 and pain.10 MT is not only appropriate for adult hospice patients; it also proven exceptionally useful in the pediatric population,11 including those with Autism spectrum disorders.12

Benefits of MT extend beyond relieving patient symptoms. It can oftentimes be associated with a reduction in stress, as reported amongst both family13 and professional caregivers. Beyond the physical/emotional benefits of MT to patients, families and caregivers, it may even offer benefit to hospices seeking cost-saving strategies. A growing body of evidence supports that MT can decrease medication and care costs (by decreasing nursing visits) for patients, offsetting the cost of MT.14


Aside from cost-savings, MT offers another benefit over medications – it has only one true contraindication: patient preference. A recent survey of U.S. hospices estimated that MT is provided as a discretionary service by over half of the hospices nationwide. Further, hospices that offer MT report that it is more often preferred by patients than any other complementary treatment method.9 If MT is not currently offered by your hospice, patients can be referred to an independent MT-BC by a prescriber. According to the American Music Therapy Association, about 20% of MT-BC receive third party reimbursement. These payers include Medicare and private insurance. Additional funding sources may include state departments of mental health and/or developmental disabilities, private auto insurance, worker’s compensation, foundations and grants.15

Although many MT-BCs work in institutional settings, home-based music therapy (HBMT) is a growing field relevant to home hospice providers. These programs can include home visits by a MT-BC and/or instruction of spouses, family members and other caregivers in selected MT techniques, which can offer lasting effectiveness and cost-savings.16 Like many growing fields, more research into the provision and implementation, as well as efficacy and cost-benefits of this innovative service are needed, but the current body of literature suggests MT is a strong addition to a hospice and/or palliative care service’s complementary and alternative treatment offering.

How to find a Board Certified Music Therapist:
Certification Board for Music Therapists
This email address is being protected from spambots. You need JavaScript enabled to view it.

American Music Therapy Association  
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1 Definition and Quotes about Music Therapy. American Music Therapy Association web site. http://www.musictherapy.org/about/quotes/. Accessed June 20, 2015.
2 McDermott O, Crellin N, Ridder HM, Orrell M. Music therapy in dementia: a narrative synthesis systematic review. Int J Geriatr Psychiatry. 2013;28:781–794
3 Ceccato E, Vigato G, Bonetto C, et al. STAM protocol in dementia: a multicenter, single-blind, randomized, and controlled trial. Am J Alzheimers Dis Other Demen. 2012;27:301-310.
4 Ray KD, Fitzsimmons S. Music-assisted bathing: making shower time easier for people with dementia. J Geront Nurs. 2014;40:9-13.
5 Bella SD, Benoit CE, Farrugia N, Schwartze M, Kotz SA. Effects of musically cued gait training in Parkinson’s disease. Ann N Y Acad Sci. 2015;1336:77-85
6 de Dreu MJ, van der Wilk AS, Poppe E, Kwakkel G. Rehabilitation, exercise therapy and music in patients with Parkinson’s disease: a meta-analysis of the effects of muscle-based movement therapy on walking ability, balance and quality of life. Parkinsonism Relat Disord. 2012;18:S114-119.
7 Haneishi E. Effects of a music therapy voice protocol on speech intelligibility, vocal acoustic measures, and mood in Parkinson’s disease. J Music Ther. 2001;38:273-290.
8 Horne-Thompson A, Grocke D. The effect of music therapy on anxiety in patients who are terminally ill. J Pall Med. 2008;11:582-590.
9 Burns DS, Perkins SM, Tong Y, Hilliard RE, Cripe LD. Music therapy is associated with family perception of more spiritual support and decreased breathing problems in cancer patients receiving hospice care. J Pain Symptom Manage. 2015. In press.
10 Krout RE. The effects of single-session music therapy interventions on the observed and self-reported levels of pain control, physical comfort, and relaxation of hospice patients. Am J Hosp Palliat Care. 2001;18:383-390.
11 Lindenfelser KJ, Hense C, McFerran K. Music therapy in pediatric palliative care: family-centered care to enhance quality of life. Am J Hosp Palliat Care. 2012;29:219-226.
12 Simpson K, Keen D. Music interventions for children with autism: a narrative review of the literature. J Autism Dev Disord. 2011;41:1507-1514.
13 Choi YK. The effect of music and progressive muscle relaxation on anxiety, fatigue, and quality of life in family caregivers of hospice patients. J Music Ther. 2010;47:53-69.
14 Romo R, Gifford L. A cost-benefit analysis of music therapy in a home hospice. Nurs Econ. 2007;25:353-358.
15 How to find a music therapist. American Music Therapy Association web site. http://www.musictherapy.org/about/find/. Accessed June 20, 2015. 16 Schmid W, Ostermann. Home-based music therapy – a systematic overview of settings and conditions for an innovative service in healthcare. BMC Health Serv Res. 2010;10:291.

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Holly Lassila, DrPH, MSEd, MPH, RPh

Domains of Wellness

What is Wellness? Merriam Webster defines wellness as “the quality or state of being healthy”. The definition of “wellness” in Mosby’s Medical Dictionary is “the dynamic state of health in which an individual progresses towards a higher level of functioning, achieving an optimum balance between internal and external environments”. In general, wellness means overall well-being and from a holistic perspective, wellness incorporates the dimensions of mental, emotional, physical, occupational, intellectual, and spiritual aspects of a person’s life. Each of these dimensions acts and interacts in ways that contribute to our quality of life.

Physical Wellness: A healthy body maintained by good nutrition, regular exercise and avoiding harmful habits.

Intellectual Wellness: A state in which our mind is open to new ideas and experiences and is engaged in the interaction with the world around us. This dimension includes the desire to learn new concepts, improve skills and seek challenges in pursuit of lifelong learning.

Emotional Wellness: The ability to understand our own feelings and cope with the challenges which life brings. Emotional wellness implies the ability to express emotions appropriately, adjust to change and cope with stress in a healthy way.

Social Wellness: The ability to relate and connect with others. Social wellness is our ability to establish and maintain positive relationships with family, friends and co-workers. Spiritual Wellness: This dimension is the ability to establish peace and harmony in our lives. It implies that life is meaningful and has a purpose and the ethics, values and morals that guide us given meaning and direction to life.

Occupational Wellness: The ability to get personal fulfillment from our professions or chosen career fields while maintaining balance in our lives. Occupational wellness means having commitment to our occupations that is satisfying and rewarding.

Environmental Wellness: The ability to recognize our own responsibility for the quality of the air, the water and the land that surrounds us.

In our own self-assessment and self-evaluation of the above dimensions we often discover certain dimensions that are balanced and others that we can improve on. Wellness is an active, lifelong process of becoming aware of choices and making decisions towards a more balanced and fulfilling life.

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Irene Petrides, PharmD

Oral Hygiene in End of Life Care

Oral mouth discomfort is often seen in advanced illness and this can strongly affect quality of life. It is therefore important to keep a close watch on a patient’s oral hygiene and make it a priority in the plan of care. Oral health issues can include but are not limited to dysphagia, nutrition and taste problems, thick mucus, difficulty speaking, denture related issues, nausea and vomiting, stomatitis, hypersalivation, mucositis, thrush, and xerostoma.1

Assessment of the patient’s self-care ability is the first step. This will help determine the level of support a patient a will require. Not all patients need full care, a simple reminder or assistance by a caretaker may provide a basic approach in order to stay on the right path of the daily oral regimen. Once a care plan is established, there are measures that can be taken in order to avoid complications which include using a soft toothbrush, avoid mouthwashes that contain alcohol, rinse with saline or soda water, or use moist gauze to wipe cheeks after each meal.2,7 In addition, it is imperative to review medications in order to rule out any undesired oral mucosa effects associated with medication therapy.1 The goal is to maintain optimal oral hygiene with minimal discomfort. Most of the time a proactive approach is desired however in hospice we are often using a palliative oral care approach in symptoms that already exist. Once preventative and standard oral hygiene procedures have been properly assessed and addressed, it may become necessary to treat common complications.

Mucositis is a painful condition that often presents as red or white lesions in the mucosal lining of mouth, pharynx and digestive tract. In the late stages it is associated with fibrosis of connective tissue and hypovascularity. It is most often seen in patients who have received toxic chemotherapy and radiotherapy in head and neck cancer.1,6 Palliative treatment includes viscous lidocaine 2%, combination oral rinse (lidocaine, diphenhydramine, sorbitol and Mylanta), and chlorhexidine gluconate.1

Oropharyngeal Candidiasis (oral thrush) is a condition where white patches can be located in the mouth, inner cheeks, throat, palate and tongue and also is associated with pain. The tissue under the white patches is often raw and sore. The patient may have bad breath, unpleasant taste in the mouth, or dry mouth. Medications that can cause thrush include corticosteroids, antibiotics, and chemotherapy. Patients who have a higher prevalence of candidiasis are those who have cancer, HIV, uncontrolled diabetes, and smokers.3,7 Treatment includes antifungal mouthwash (nsystatin) or lozenges (clotrimazole). Administration of systemic fluconazole or itraconazole may be necessary in the management of more severe cases.1 It is important to remember that if a patient wears dentures they must also be treated separately with antifungal mouth rinse.5

Xerostoma is a symptom referring to dry mouth. Nearly 75% of hospice patients are affected by xerostoma, which is the most common cause of malnutrition in palliative patients. It is often associated with difficulty chewing, altered taste burning sensation, and thick saliva.1,3 Causes of xerostoma may include dehydration, vomiting or diarrhea, medications with anticholinergic activity, benzodiazepines and opioids, radiation, HIV/ AIDS, diabetes, renal failure, and Sjogrens syndrome.1,3 Treatment includes oral hydration such as humidifiers, stimulating salivary reflexes with medications like xylitol, administration of the cholinergic agonist pilocarpine, or using saliva substitutes such Biotene®.

Hypersalivation also known as sialorrhea is an increase in salivary flow. Patients who have neurological conditions such as Parkinson’s disease or amyotrophic lateral sclerosis may find it difficult to manage hypersalivation. Often medications are contraindicated in the treatment due to the side effects associated with anticholinergic drugs. If the patient’s quality of life is affected, anticholinergic medications such as atropine, glycopyrrolate, or scopolamine can be used.1

Dysphagia, or difficulty swallowing effectively, is a common symptom seen in hospice care. Food debris and saliva accumulate in the oral cavity which can increase bacterial growth. Inadequate oral hygiene at this point in care may increase the patient’s risk of developing aspiration.4 Therefore dysphagia may not only have a negative impact on oral health but also on the systemic health of a hospice patient. Despite minimizing debris in the oral cavity with adequate oral hygiene other preventative measures are necessary in order to avoid undesired complications. The most common non-invasive approaches include pleasure feeding, pureed diet, and crushing medications.1,4

Awareness of oral hygiene in the hospice patient should be an extension of the palliative care plan. Identifying oral health barriers, preventing major complications and treating oral conditions is the mainstay of managing oral hygiene. In conclusion comfort care and palliative treatment are established in oral care if a patient can eat and drink adequately with minimal pain or discomfort.


1. Mulk BS, Chintamaneni RL, Mpv P, Gummadapu S, Salvadhi SS. Palliative Dental Care- A Boon for Debilitating. Journal of Clinical and Diagnostic Research : JCDR. 2014;8(6):ZE01-ZE06. doi:10.7860/JCDR/2014/8898.4427.

2. Chen X, Chen H, Douglas C, Preisser JS, Shuman SK. Dental treatment intensity in frail older adults in the last year of life. Journal of the American Dental Association (1939). 2013;144(11):1234-1242.

3. Alt-Epping B, Nejad RK, Jung K, Groß U, Nauck F. Symptoms of the oral cavity and their association with local microbiological and clinical findings—a prospective survey in palliative care. Supportive Care in Cancer. 2012;20(3):531-537. doi:10.1007/s00520-011-1114-z.

4. Gallagher R. Swallowing difficulties: A prognostic signpost. Canadian Family Physician. 2011;57(12):1407-1409.

5. Saini R, Marawar P, Shete S, Saini S, Mani A. Dental Expression and Role in Palliative Treatment. Indian Journal of Palliative Care. 2009;15(1):26-29. doi:10.4103/0973-1075.53508.

6. Davies, Andrew, and Ilora G. Finlay, eds. Oral care in advanced disease. Oxford University Press, 2005.

7. O’Reilly M. Oral care of the critically ill: a review of the literature and guidelines for practice. Australian Critical Care. 2003;16(3):101-110. doi:10.1016/s1036-7314(03)80007-3.

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Michelle Mikus, PharmD

POEMS: Patient Oriented Evidence that Matters

We’ve entered a time where everything can be searched on the internet, and now patients have wanted to be more involved in their medical treatment than ever before. Talking to a patient and their families and caregivers is often quite different than talking to another healthcare professional and begs the question “What is important to both patient and medical provider?” That is where Patient Oriented Evidence that Matters (POEMs) comes into play.

Two practitioners introduced the POEMs concept into medicine: David Slawson and Allen Shaughnessy from the University of Virginia. They actually came up with the concept from a formula: U = R·V / W. The formula seeks to equate the information doctors find to its usefulness. In short, the more relevant (R) and valid (V) the information is and the less work (W) it takes to find correlates with higher usefulness (U). With the internet at everyone’s fingertips, practitioners are suffering from “the information paradox” as Muir Gray from the National Electronic Library of Health states, which is described as so much information that they may not be able to find what they need when they need it. This is where POEMs can be useful.

POEMs must meet three criteria: a) address a question that a doctor encounters, b) measure outcomes that doctors AND their patients care about (symptoms, morbidity, mortality, QOL), and c) have the potential to change the way doctors practice. Conventional journal articles outline in high detail specifics about clinical manifestations, however this is not language that the layperson can understand nor will it ultimately affect them. Often journal articles do not ultimately answer a question. The advantage of POEMs includes communication that is centered on what really matters to the patient in a way that is meaningful to the doctor also. A typical POEM report would pose the patient specific question and then provide a bottom line before going into detail. This summary format makes them quite user friendly.

Evidence-based medicine, by definition, integrates patient values and expectations as a core feature along with both individual clinical expertise and the best external evidence. It is a process that starts with the patient presentation/question and ends with the incorporation of findings into the patient’s care, but in the middle includes literature searches and evaluations. By focusing the search and evaluation steps on POEMs, the patient will remain at the center of the care. In addition, information discovered has the potential to be more relevant and valid while requiring less work.

Sample POEM with hospice focus Olanzapine for intractable nausea and vomiting:

Clinical Question: What can be used to treat intractable nausea that has been refractory to conventional nausea medications?

Bottom Line: Olanzapine (Zyprexa) has been found to very effectively control nausea due to its broad spectrum of activity at a dose of 5mg at bedtime.

Reference: Atkinson SR. Olanzapine for intractable nausea and vomiting in palliative care patients not receiving chemotherapy. J Palliat Med. 2014 May;17(5):503-4

Study Design: Retrospective review

Setting: Palliative care

Synopsis: Multiple studies have shown olanzapine to be effective for chemotherapy induced nausea and vomiting however none had previously studied the drug for non-chemotherapy receiving patients with intractable nausea. This type of nausea reduces the quality of life for patients and often results in multiple trials of different medications—sometimes in combination. Patients averaging 65 years in age that were not receiving chemotherapy were initiated scheduled olanzapine 5mg at bedtime. The need for other anti-emetics and rescue anti-emetics was significantly reduced and there were no extrapyramidal side effects reported. One patient required a reduction in dose to 2.5mg at bedtime due to somnolence. Overall, olanzapine has proven again to be effective in addition to being cost effective and its use in intractable nausea and vomiting will reduce drug interactions and polypharmacy.


1. Shaughnessy AF, Slawson DC, Bennett JH. Becoming an information master: a guidebook to the medical information jungle. J Fam Pract. 1994;39:489-499.

2. Smith, Richard. A POEM a week for the BMJ. BMJ 2002;325:983 3. Smith, Richard. What clinical information do doctors need? BMJ 1996;313:1062-1068.

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Delta Campus Pharmacy Student

Management of Pruritus from a Hepatic Etiology

Pruritus is a common symptom experienced by many patients in palliative and hospice care which can dramatically affect a patient’s comfort and quality of life even though it is not the most prevalent symptom such as pain or dyspnea. While the complete pathology of all causes of pruritus is not yet completely understood, the itching sensation is best relieved by properly treating the underlying etiology if it is known.1

Pruritus has been associated with both malignant disease as well as nonmalignant chronic diseases such as renal, thyroid, and hepatic disease. A Cochrane Review found that about one third of all patients with end stage renal disease not on hemodialysis and 70%-80% of patients receiving hemodialysis experience significant pruritus. The same review found that nearly 100% of patients with biliary cirrhosis had a cholestatic pruritus.1 According to the guidelines from the American Association for the Study of Liver Diseases, cholestatic pruritus is often times the initial symptom in half of the patients with biliary cirrhosis.1,2

There exist many therapies that could be used to treat pruritus in general such as antihistamines like hydroxyzine, opioid receptor antagonists similar to naloxone, direct serotonergic agents such as ondansetron, selective serotonin reuptake inhibitors (SSRI’s) such as paroxetine and sertraline, antiepileptics such as gabapentin, and the antibiotic rifampicin. Most of these agents have different mechanisms against pruritus which may be more or less effective given certain patient factors. The American Association for the Study of Liver Diseases guidelines for primary biliary cirrhosis recommend several agents for the treatment of cholestatic pruritus:1,2

Bile Acid Sequestrants: The first line therapy recommendation is to use a bile acid sequestrant agent. Bile acid sequestrants are approved for the treatment of dyslipidemias by functioning as a resin that traps cholesterol and other acids from bile in the GI tract which can allow passing of these substances out through the GI tract instead of being systemically reabsorbed. It is believed that forcing the elimination of these bile acids will also relieve cholestatic pruritus. The bile acid sequestrant of choice is cholestyramine dosed at 4 grams per dose with a maximum dose of 16 grams daily. [The other currently available bile acid sequestrants, colesevelam, and colestipol, have not been studied and currently contain no recommendations for the treatment of pruritis.2] Complications of bile acid sequestrant therapy include gastrointestinal disturbances (constipation, loose stool, cramping, excessive flatus, etc.) and the prevention of drug absorption in the GI tract since acidic drugs will also be trapped by the resin.1,2 It is recommended to separate the administration of a bile acid sequestrant from other medications by 2-4 hours.

Antidepressants: It is believed that serotoninergic activity contributes to signal transduction of pruritus. Several antidepressants have been tested including paroxetine, doxepin, and sertraline. Sertraline 75 mg to 100 mg is the preferred therapy for cholestatic pruritus according to the guidelines by the American Association for the Study of Liver Disease.2 General pruritus relief has been noticed with paroxetine 5 mg to 10 mg at night for multiple etiologies including hepatic and renal disease.1 Doxepin appears to be effective at doses of 25 mg daily, however tricyclic antidepressants tend to have anticholinergic activity which can cause adverse effects in older patients and should be avoided unless necessary.1,3 Relief of pruritus by antidepressants is usually seen in 24 to 48 hours, much sooner than the antidepressant effects of these agents.1 Ondansetron has been studied as a direct acting serotonergic agent, however it has only shown mild to no benefit in clinical trials.1,2

Rifampicin: Rifampicin is an antibiotic and hepatic enzyme inducer shown in several trials and meta-analyses to relieve hepatic pruritus. Recommended dose is 150-300 mg twice daily depending on serum bilirubin (300 mg for bilirubin less than 3 mg/dL and 150 mg for bilirubin 3 mg/dL or higher). Complications of therapy include drug induced hepatotoxicity or renal impairment and hepatic ennzyme induction which could decrease the efficacy of other medication therapies.1,2 Due to the risks for hepatotoxicity and nephrotoxicity, liver and renal function tests will need to be continually monitored suggesting that therapy with rifampicin should be held in reserve for when benefit outweighs risk in end-of-life care.

Opioid Antagonists: While there is strong evidence for the use of the opioid antagonists naloxone or naltrexone, these therapies are usually inappropriate in hospice care since these agents will counter the analgesic activity of other opioids used in the treatment of chronic pain and could also induce opiate withdrawal.1,2 In addition, naltrexone has a rare potential for causing hepatotoxicity which will require monitoring liver function. The recommended dose of naltrexone is 50 mg by mouth daily, however naltrexone is hepatically eliminated and will accumulate in decompensated and end-stage liver disease requiring that the dose of naltrexone be decreased.2 Due to the monitoring burden and the risk of counteracting chronic opiate activity, it is recommended only to use naltrexone when the patient is not taking opioid analgesics and benefit outweighs risk of decreasing liver function.

Antihistamines: The mechanism of antihistaminergic compounds is reliant on non-specific antipruritic effects with little treatment to the direct etiology of hepatic pruritus.2 Complications that occur are the risk of confusion, sedation, exacerbation of dementias, and increase in fall potential for patients that are still ambulatory from the anticholinergic activity of the antihistamine agents similar to diphenhydramine and hydroxyzine.3 It is recommended to use these only when other systemic therapies have failed or are inappropriate.

Phenobarbital: Phenobarbital was once utilized as a therapy for hepatic pruritus, however its use is limited in modern practice due to risks of severe sedation and hepatic enzyme induction.2,3

There is a large variety of medication therapies that can be used to treat pruritus from a hepatic etiology. Topical therapies such as the counter-irritants capsacin or menthol have some limited efficacy1 but the application area may become so large in advanced disease that their use becomes impractical. While conventional therapies of systemic antihistamines may be moderately effective, they have the potential for undesirable adverse events and may be less effective or efficient than an etiology specific agent. Cholestyramine or sertraline may not be the first agent that comes to mind when a patient complains of an itch, however these less conventional therapies have become a mainstay for the treatment of pruritus in advanced hepatic disease. In addition, the use of these alternate therapies broadens the spectrum of drugs that could be used for multiple pharmacological effects and can afford a patient specific drug selection.

Submitted by: James R. Thomas, PharmD., BS Hospice Clinical Pharmacist and Pharmacy Resident at Delta Care Rx


1. Xander, C., Meerpohl, J. J., Galandi, D., Buroh, S., Schwarzer, G., Antes, G., & Becker, G. (2013). Pharmacological interventions for pruritus in adult palliative care patients. The Cochrane Database of Systematic Reviews, 6(6), CD008320. doi:10.1002/14651858.CD008320.pub2

2. Lindor, K. D., Gershwin, M. E., Poupon, R., Kaplan, M., Bergasa, N. V., & Heathcote, E. J. (2009). Primary biliary cirrhosis. Hepatology. doi:10.1002/hep.22906

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Lori Osso-Connor, PharmD, CGP

Role of Warfarin in Hospice and Palliative Care

Patients who make the hospice choice have opted for comfort measures and are no longer seeking life sustaining treatment. However, as hospice professionals encounter daily, many patients are admitted on medications that are considered treatment and are used for curative measures and not palliative measures.

The risk for thromboembolism in hospice and palliative care patients increases due to advanced age and diagnoses such as cancer or cardiomyopathy. Warfarin (Coumadin®) is indicated as treatment to prevent clotting in atrial fibrillation, thromboembolic disease, and artificial heart valves. It is a medication that poses a clinical challenge on whether to continue or discontinue when the patient becomes hospice appropriate. Warfarin’s mechanism of action is to inhibit Vitamin K epoxide reductase which decreases the Vitamin K in the body and decreases clotting. While warfarin is typically indicated as treatment, it could be argued that it is used in hospice and palliative care to provide comfort by reducing the risk of pain and swelling in the extremities due to DVT, unilateral weakness, or paralysis related to stroke.

However, there are several arguments that can be made to support the discontinuation of warfarin in hospice and palliative care. Some issues to consider include:

• The use of warfarin requires PT/INR lab work to ensure therapeutic efficacy. Studies have shown that hospice and palliative care patients require more frequent INR monitoring. These blood draws may be undesirable to the patient and or caregivers at this point in care. Additionally, poor venous access may make obtaining the blood difficult.

• Warfarin is a medication that has many drug-drug interactions including many antibiotics and drug-dietary interactions which could pose unnecessary complications to the patient. Some examples of drug–drug interactions with warfarin in which the anticoagulant effect is increased include levofloxacin (Levaquin ®), sulfamethoxazole/ trimethoprim (Bactrim ®), prednisone, and NSAIDS. In addition, Vitamin K rich foods may decrease the effects of warfarin. Therefore, it is most important to keep a consistent type diet.

• As intake declines or is erratic, the dietary vitamin K may fluctuate which could increase the risk of a bleed or clot.

• Nausea and vomiting could impact the medication adherence which may alter INR due to drug interactions.

• When a dose is changed, it takes 5-6 days to take full effect. If the PT/INR is not carefully managed, it leads to additional increases or decreases in the dose and a myriad of additional blood draws.

• The risk of an intracranial hemorrhage in a debilitated ambulatory patient who may fall is greater than the benefit in preventing a stroke.3

• The risk of a GI hemorrhage is about 8%.1

• The 1-year risk of stroke in atrial fibrillation is 2% in patients treated with warfarin and 4% in those untreated.1

Do the benefits of continuing outweigh the risks? Some factors to consider when facing this decision include: indication, prognosis, bleeding risk, thrombosis risk, nutritional status, appropriate monitoring, medication adherence, medication changes, and patient/family preferences. It is also important to consider whether a new clot will impair the patient’s function or quality of life. As one can see, the choice to discontinue warfarin is a difficult one and is not always clear cut. The risks verse the benefits in each patient must be assessed in accordance with the family and patient’s goals. This individualized approach will help the hospice care professional determine whether the benefits outweigh the risks to the patient and make an appropriate choice.


1. Allen, Richard. “10 Drugs to Reconsider When a Patient Enrolls in Hospice.” NHPCO Newsline(2014): 5.

2. Hill, Robin, Kerri Martinez, Thomas Delate, and Daniel Witt. “A Descriptive Evaluation of Warfarin Use in Patients Receiving Hospice or Palliative Care Services.” Journal of Thrombosis and Thrombolysis 27.3 (2008): 334-39.

3. Von Gunten, Charles, David Weissman, and Janet Abraham. “Fast Fact #278 Warfarin and Palliative Care.” #278 Warfarin And Palliative Care. Web. 26 Feb. 2015

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Char Cole, PharmD, CGP

Impact of Bariatric Surgery on End of Life Care Symptom Management

Obesity is a growing concern in the United States. There are three major types of bariatric surgery done in the United States to combat the obesity problem.

1. Vertical Banded (Stapled) Gastroplasty

2. Adjustable Gastric Banding

3. Roux-en-Y Gastric Bypass

Weight loss occurs by causing malabsorption or by restricting gastric volume or a combination of both. Banding procedures limit the amount of intake, whereas the Roux-en-Y procedure not only reduces the stomach size, it also changes the site of attachment of the small intestine. The Roux-en-Y procedure bypasses the lower portion of the stomach and a much smaller stomach pouch (15-30 mL capacity) is created, then the small intestine (the entire duodenum and part of the proximal jejunum) is removed from the lower stomach and attached to the newly formed stomach pouch. This procedure reduces the surface area that is available for absorption of nutrients and medications.

Different medications have different requirements for absorption and ultimately effectiveness. Medications in aqueous solution are more rapidly absorbed then those in oily solutions. Medications are soluble at different pH levels. Different medications that are more soluble at acidic pH are absorbed in the stomach, whereas medications that are more soluble at alkaline pH are absorbed in the small intestine. Intestinal enzymes are also necessary for the absorption of some medications. The Roux-en-Y Gastric Bypass can alter medication absorption.

Reducing the amount of time needed for absorption of the medication is essential for safe and effective use of medications. The formulation of the medication can be sufficient to reduce the amount of time needed in the stomach/small intestine for absorption. When possible the use of pills that can be crushed should be considered, as well as liquids, subcutaneous, intravenous, rectal, vaginal, intranasal and transdermal formulation and/or routes of administration should be considered. Avoid or use with caution any medication that has a long stomach absorptive phase.

Oral non-steroidal anti-inflammatory drugs (NSAIDs), salicylates and bisphosphonates should be avoided. These medications can cause or increase the potential of the patient to develop ulcers in the new much smaller stomach and/or reduced small intestines in all types of bariatric surgery. If the use of these medications are essential, then consider alternative routes of administration such as topical or injectable. Delayed release preparations of all medications such as CR, SR, XR, LA, EC, etc. should be avoided in Roux-en-Y Gastric Bypass.

Pain management in end of life care is essential. The use of MS Contin or morphine ER should be avoided in patients that have had a Roux-en-Y Gastric Bypass. Due to the reduced surface area of the gastrointestinal tract, the use of immediate release formulations would be a better alternative to extended release preparations. The use of immediate release formulations or non-extended release formulations may require a more frequent dosing schedule; however the Roux-en-Y bypass patient will be more apt to achieve more consistent pain management.

It is important to inform all healthcare providers of a patient’s bariatric surgical history if it exists as this will alter the medication therapy chosen for the patient. The length of time the patient is status post bariatric surgery has no impact to the medication therapy consideration. Once a patient has had bariatric surgery, medications will always need to be adjusted to take into account the changes made to the gastrointestinal tract through the bariatric surgery and how this will alter the absorption of medications. All medication therapies chosen for a bariatric surgery patient should be evaluated for effectiveness and for the increased potential for side effects if the proper monitoring is not done.


1. Vanhoose K. Medication Absorption after Gastric Bypass. Advance Healthcare Network for NPs and PAs. www.ADVANCEforNPs\&Pas\_PrinterFriendly.htm

2. Rogula T, Schauer P. Medications after Bariatric Surgery. www.Medicationsafterbariatricsurgery.htm

3. Miller AD, Smith KM. Medication and Nutrient Administration Considerations after Bariatric Surgery. AM J Health Syst Pharm.2006;63(19):1852-1857.

4. Lawrecki T. How is drug absorption altered by bariatric surgery? University of Illinois Chicago College of Pharmacy

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Delta Campus Pharmacy Student

Tramadol Induced Hypoglycemia: The Latest Consideration for Tramadol in Pain Therapy

Tramadol, a weak opioid analgesic, is primarily popular for its two separate and distinct mechanisms associated with pain management. As an opioid, it inherently binds to the mu-opioid receptor to induce analgesia. But its additional effect results in inhibition of the serotonin and norepinephrine receptors. The latter is believed to play a role in the treatment of neuropathic pain, as this type of pain is believed to be associated with a malfunction of the peripheral or central nervous system.1 Because of this dual mechanism and a general perception that tramadol is safer than most existing opioids, prescribing has grown significantly in recent years.

Like most other therapeutic alternatives in pain treatment, however, it is not free of potentially life-threatening adverse effects. Tramadol carries a risk for the development of serotonin syndrome, a condition characteristic of hyperthermia, irregular heartbeat, organ failure, and death, due to the potential for accumulation of serotonin in the body, as well as a notable risk of seizures, both possible even at therapeutic doses.2 These risks are greatly increased when co-administered with serotonin modulators, such as selective-serotonin reuptake inhibitors, serotonin norepinephrine reuptake inhibitors, tricyclic antidepressants, and antimigraine medications, among others.3

Additionally, tramadol still maintains a similar profile of abuse potential compared to other opioid analgesics. The reclassification of tramadol to schedule IV under the US Controlled Substances act in August of 2014 echoes the emerging association of abuse witnessed from the increased use in practice.2

As of recent, a group of researchers based in Canada and France have now raised a new concern for the use of tramadol in pain therapy. Tramadol has been identified with an increased chance of hospitalization for hypoglycemic episodes, according to researchers. Tramadol administration resulted in a 52% increase in risk of hospitalization for hypoglycemia. The recent study published in December 2014 by Fournier, et al., investigated the growing trend in tramadol-induced hypoglycemia.

A trial conducted within the United Kingdom Clinical Practice Research Datalink (CPRD) linked to the Hospital Episode Statistics (HES) database with an enlisted cohort of 334,034 patients compared the risk of hypoglycemia in patients treated with tramadol versus codeine for non-cancer pain from 1998 to 2012. Selected patients were at least 18 years of age with at least one year of baseline medical history in the CPRD and HES, which covers 13 million patients and over 680 practices in the United Kingdom. Included patients were limited to those newly initiating single opioid therapy with tramadol or codeine.

Typical pain treatment in this population included headache, neuralgia, abdominal and pelvic pain, musculoskeletal pain, injury and/or trauma, and surgery. Additionally, all cases of pain related to cancer were preclusive to inclusion. Within this cohort, 1,105 patients were hospitalized for hypoglycemia at follow-up intervals during the study period. All hospitalized patients were compared to 11,019 controls based on 10 controls on age, sex, and duration of follow-up. The resulting analysis identified an association between tramadol administration and increased risk of hospitalization for hypoglycemia versus the use of codeine (OR 1.52, 95% CI 1.09-2.10). Additional findings of the study noted a trend towards increased risk of hospitalization within the first 30 days of therapy in tramadol versus codeine use (OR 2.61, 95% CI 1.61-4.23).1 This casual relationship identified in early initiation of therapy warrants increased awareness of patient monitoring to avoid potentially life-threatening episodes of hypoglycemia.

It is evident that these findings create a conversation piece regarding the therapeutic use of tramadol, particularly in the growing prevalence of the need to treat diabetic neuropathy. In addition to the concern for opioid-induced adverse reactions, seizures, and a number of drug interactions, the risk for hypoglycemic episodes suggests much more consideration from the prescriber when selecting analgesic therapy, especially when initiating therapy for the first time. Serotonin syndrome poses an additional concern due to the highly prevalent use of serotonin-regulating medications in the (i.e. duloxetine, TCAs, trazodone, etc.), especially in the hospice setting. This, coupled with the risk for hypoglycemia, may lead to unintended consequences in the already vulnerable hospice population. The use of tramadol in hospice still remains less than what is observed in practice of other populations. Nonetheless, as time passes the hospice industry will likely notice increased use due to the pressure of opioid use reform in the United States.

While the authors advised that further research is needed to determine a stronger link, the sheer prevalence of use in practice warrants extra patient consideration. As stated by Nelson L, and Juurlink D, “If we replace conventional opioids with tramadol, as some guidelines have suggested, we may be left with more unintended consequences of the opioid epidemic to worry about.”2

Submitted by: Christopher Smurthwaite, PharmD Candidate at Duquesne University and Mary Mihalyo, B.S., PharmD, CGP, BCPS, CEO at Delta Care Rx


1. Fournier J, Azoulay L, Yin H, Montastruc J, Suissa S. Tramadol use and the risk of hospitalization for hypoglycemia in patients with noncancer pain. JAMA Intern Med. Published online 8 December 2014. doi:10.1001/jamainternmed.2014.6512. Accessed 24 January 2015.

2. Nelson LS, Juurlink DN. Tramadol and hypoglycemia: one more thing to worry about. JAMA Intern Med. Published online December 08, 2014. doi:10.1001/jamainternmed.2014.5260. Accessed 24 January 2015.

3. Sindrup SH, Ott M, Finnerup MO, et al. Antidepressents in the treatment of neuropathic pain. Basic & Clinical Pharmacology & Toxicology. Published online 9 August, 2005. Accessed 24 January 2015

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Delta Campus Pharmacy Student

Comparison of Insulin Therapies

BACKGROUND: Insulin is a common therapy in the treatment of diabetes mellitus type 1 and 2. With the advent of intermediate-acting and long-acting insulin products, basal insulin therapy has become a common practice usually utilized to reduce the number of injections needed to administer or in combination with a short-acting insulin product in the basal–bolus insulin regimens.

The original insulins created to have longer durations of action were the NPH insulins which utilized a crystalline complex between the insulin and protamine.2 In more recent years, newer basal insulins such as Levemir and Lantus have come onto the market which do not rely on the use of protamine-insulin complexes and also claim to last longer (possibly up to single dose a day administration) with no peak activity. The lack of peak activity promises to reduce hypoglycemia risk and to provide a more basal-like dosing.1,3 The original insulins used as bolus insulin therapy were isolated from either animal or human sources. Today, the standard of isolated insulin therapies is regular human insulin. Like the long acting insulin products, recent years have seen the emergence of rapid acting insulin analogues. These rapid insulins promise to have higher efficacy and safety due to rapid onset (for meal time administration) and shorter duration of action.1,4,5

While the newer insulin products claim to have benefits of duration of action and less risk of hypoglycemia, they come at a higher cost than the regular human insulin and NPH insulin products. The average patient admitted to hospice care usually does not have insulin therapy related to the terminal diagnosis — with some obvious exceptions such as pancreatic cancer. The following is an analysis of the benefits and claimed convenience of the newer designer insulin analogues and how they could be substituted with regular human insulin and NPH insulin.

COMPARATIVE ANALYSIS: All three insulins (glarginine, detemir, and NPH) appear to have an onset of 1 to 2 hours. Peak efficacy of Levemir is at a narrow range of 6 to 8 hours (in graphic data in package insert; the analysis section states that there is “no pronounced peak”) versus a more unpredictable reported peak between 3 and 12 hours of Humulin N. Lantus appears to have the most data to support the assertion that there is no pronounced peak of activity with full onset occurring around 4-5 hours after administration and remaining constant throughout the duration of the trials. Duration of action appears to be similar between NPH and Levemir treatments which officially list their durations of action in package inserts as “up to 24 hours.”2,3 Lantus claims to have a constant level up to 24 hours as well, however all data collection ended at 24 hours demonstrating that it could have a greater than 24 hours duration.15

The variable ranges of duration of action and time to peak pharmacodynamic response could be affected by multiple factors such as patient metabolism, site of administration, administration technique, storage conditions of the product, etc. It appears that the NPH insulin (Humulin N) would be more prone to administration technique errors due to the necessity to remember to resuspend the crystalline suspension dosage form by rolling the vials prior to administration. While Lantus has no particularly documented half-life, Levemir has a similar but slightly greater half-life than NPH which could be the result of its being albumin bound which protects some of the insulin from clearance.6,7 There does not appear to be data readily available on the effects of insulin detemir in patients with hypoalbuminemia which is a common condition as a patient's nutritional status declines in end-of life care.

For hypoglycemia risk, the current American Diabetes Association guidelines state that NPH insulin has a higher risk of hypoglycemia over the newer basal insulins Levemir and Lantus. However, in comparative trials, only one case of severe hypoglycemia will be prevented for every thirty-seven patients treated with Levemir than if all thirty-seven patients were to receive NPH. In the case of non-severe hypoglycemia, the risk was similar between Levemir and NPH.3 In trials of Lantus vs NPH both combined with regular human insulin as a bolus, Lantus would need to be used in 97 patients than if they were treated with NPH in order to prevent only one case of severe hypoglycemia.15

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2016 06 29 14 48 18

RESULTS: Given the similar onset, peak, and duration, Humulin N properly dosed twice daily could be used as a treatment alternative to Levemir or Lantus as a basal insulin alternative. While the newer insulins have a significantly less pronounced peak than NPH insulin,2,3,15 Humulin N has a long enough duration of action to be utilized as a longer acting insulin replacement therapy. It appears that hypoglycemia risk is similar between all three insulin therapies. However, it should be noted that Levemir and Lantus have been shown to have a more predictable pharmacodynamic profile over NPH insulin — not more effective6 — and that NPH insulin has the potential for hypersensitivity to the protamine. Regardless, all three insulin therapies can be considered equiefficacious (not equipotent) and can be utilized as basal insulin supplementation.

CONCLUSIONS: The choice between any of the available insulin products appears to be mostly based on clinical safety instead of clinical efficacy. The data suggests that any basal-bolus regimen can be considered equiefficacious if properly managed. The selection on which agents to use for outpatient therapy may need to take into account some of those minute differences in safety or dosing depending on individual patient factors. While true, once a day dosing of Lantus or Levemir may seem appealing since it reduces the number of invasive injections during palliative care, the need for basal insulin therapy decreases as nutritional intake declines. In addition, the existence of mixed human insulin products (Novolin 70/30 and Humulin 70/30) may increase convenience since they can provide both bolus coverage and basal insulin in only one or two administrations a day and can be more easily adjusted for changes in intake than the pure basal therapies. Utilization of the older human insulin products can be beneficial from a cost-effectiveness potential especially in the hospice industry since regular human and NPH insulin are available as a lower cost alternative. The cost-effectiveness of human insulin products can be significant since most hospices will not usually have sufficient insulin utilization for purchasing power as some larger health care institutions.


1. American Diabetes Association. Standards of medical care in diabetes–2014. Diabetes Care. 2014;37 Suppl 1:S14-80.

2. Eli Lilly . Humulin N [package insert] 2013.

3. Novo Nordisk. Levemir [package insert] 2013.

4. Novo Nordisk. Novolog [package insert] 2014.

5. Sanofi-Aventis. Apidra [package insert] 2014.

6. Heise T, Nosek L, Rønn BB, et al. Lower within-subject variability of insulin detemir in comparison to nph insulin and insulin glargine in people with type 1 diabetes. Diabetes. 2004;53:1614-20.

7. Brunner GA, Sendhofer G, Wutte A, et al. Pharmacokinetic and pharmacodynamic properties of long-acting insulin analogue nn304 in comparison to nph insulin in humans. Exp Clin Endocrinol Diabetes. 2000;108:100-5.

8. American Diabetes Association . Insulin administration. Diabetes Care. 2004;27 Suppl 1:S106-9.

9. Goldman-Levine JD, Lee KW. Insulin detemir–a new basal insulin analog. Ann Pharmacother. 2005;39:502-7.

10. Eli Lilly . Humulin R [package insert] 2013.

11. Novo Nordisk. Novolin R [package insert] 2013.

12. Ratner R, Wynne A, Nakhle S, Brusco O, Vlajnic A, Rendell M. Influence of preprandial vs. postprandial insulin glulisine on weight and glycaemic control in patients initiating basalbolus regimen for type 2 diabetes: a multicenter, randomized, parallel, open-label study (nct00135096). Diabetes Obes Metab. 2011;13:1142-8.

13. Meyer C, Boron A, Plummer E, Voltchenok M, Vedda R. Glulisine versus human regular insulin in combination with glargine in noncritically ill hospitalized patients with type 2 diabetes: a randomized double-blind study. Diabetes Care. 2010;33:2496-501.

14. Umpierrez GE, Hor T, Smiley D, et al. Comparison of inpatient insulin regimens with detemir plus aspart versus neutral protamine hagedorn plus regular in medical patients with type 2 diabetes. J Clin Endocrinol Metab. 2009;94:564-9.

15. Sanofi . Lantus [package insert] 2013.

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Holly Lassila, DrPH, MSEd, MPH, RPh

Health Literacy: Do Patients Really Understand What We Are Communicating?

The definitions of literacy range from the Merriam Webster definition of the “ability to read and write” to the National Literacy Act of 1991 definition of “an individual’s ability to read, write and speak English and compute and solve problems at levels of proficiency necessary to function on the job and in society, to achieve one’s goals, and to develop one’s knowledge and potential.” Functional health literacy can be distinguished from literacy as the “ability to read and comprehend prescription bottles, appointment slips, and the other essential health-related materials required to successfully function as a patient.”3

Poor health literacy affects people of all ages, races, incomes and education levels and affects 36% of U.S. adults.4 According to Doak et al, the average American reads at an 8th or 9th grade level; however, most health care materials are written on a 10th grade level.5 Poor health literacy is of great concern within a public health context as demonstrated by the inclusion of “increasing health literacy skills” as one of the objectives in the Healthy People 2020 goals.

Basic health literacy is fundamental to the success of each interaction between health care professionals and patients. Low health literacy may result in poor self-care management, increased disability and morbidity, and adverse health outcomes such as ED visits and hospitalizations.4

Health care professionals working in hospice are often educating not only the patient but the caregivers and other support systems for the patient. Being aware of available tools can aid in supporting patients and families. Health communication materials which may be helpful include:

1. SIMPLY PUT: A guide for creating easy-to-understand materials. This is a publication developed by the Centers for Disease Control and Prevention which highlights many best practices regarding assessing and creating written information for the public on almost any scientific subject. [http://www.cdc.gov/healthliteracy/pdf/Simply_Put.pdf]

2. ASK ME 3: This is an educational program designed by the National Patient Safety Foundation to improve communication between patients and health care providers and encourage patients and caregivers to become active members of their health care team. [https://npsf.siteym.com/?page=askme3]

3. SCRIPT YOUR FUTURE: This is a campaign designed to help patients become adherent with taking their prescribed medication regimens. Some of the tools included allow the health care provider and patient to personalize health literacy interventions regarding medication adherence and education. [http://www.scriptyourfuture.org/]

Communicating with patients is a large component of clinical practice. Being well versed in cultural competence, understanding socioeconomic factors, a patients/caregivers education level, and patient’s priorities or motivations can be powerful tools in the promotion of health literacy and clear communication.


1. Merriam Webster: An Encyclopedia Britannica Company. Available at: http://www.merriam-webster.com/dictionary/literate. Accessed December 15, 2014.

2. National Literacy Act of 1991. Available at: https://www.govtrack.us/congress/bills/102/hr751. Accessed December 15, 2014.

3. Ad Hoc Committee on Health Literacy for the Council on Scientific Affairs, American Medical Association. Health Literacy: Report of the Council on Scientific Affairs. JAMA. 1999; 281(6):552-557.

4. U.S. Department of Health and Human Services. Office of Disease Prevention and Health Promotion. Healthy People 2020. Washington, DC. Available at http://www.healthypeople.gov/2020/topicsobjectives2020/default.aspx. Accessed December 15, 2014.. 5. Doak CC, Doak LG, Root JH. The literacy problem in teaching patients with low literacy skills. 2nd ed. Philadelphia, PA: JB Lippincott Co; 1996.

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Michelle Mikus, PharmD

Death with Dignity: An Overview & Legislative Update

Death with Dignity has become a household phrase since People magazine published young Brittany Maynard’s story concerning the issue. As a result of her emotional experience and story, Death with Dignity and “right to die” proponents all over the country have been refueled to get bills passed and laws put in place giving certain terminally ill patients the choice to end their own lives. Working in their favor are five states that already allow patients the right to die: Oregon (law passed in 1994), Washington (2008), Montana (2009), Vermont (2013), and New Mexico (2014). It should be noted that in both Montana and New Mexico a court case must be involved before being deemed lawful. Because of this, there is not much utilization.

In the three states that have laws allowing physician assisted suicide, certain criteria must be met in order to receive a prescription for the necessary medications:

1. Patient must be a resident of Oregon, Washington, or Vermont.

2. Patient must be 18 or more years old.

3. Patient must be capable of making health care decisions for themselves.

4. Patient must be diagnosed with a terminal illness that will result in death within six months.

5. Two physicians must evaluate that all above criteria is met.

In addition to all criteria being met, there are waiting periods before some of the steps can be accomplished. This includes the longest waiting period of 15 days between the first and second oral requests to the physician. In addition, there is a 48-hour waiting period before the prescribed medications can be picked up at a pharmacy.

In December of 2014, Medscape published an ethics report focused on “Life, Death, and Pain” that was given to 21,531 physicians in both the US and Europe. The very first question was “Should physician-assisted suicide be allowed?” The results in favor of allowing this were 54%, which is an 8% increase since the 2010 survey asking the same question (statistics from the US physicians only). Not far off from these physician results are results from a recent Gallup poll, in which 58% of Americans answered in favor of physician assisted suicide and 7 out of 10 were in favor of euthanasia for terminally ill patients.

Many states have legislation in the works to allow Death with Dignity acts similar to Oregon’s. States include: Connecticut, Hawaii, Kansas, New Jersey, and Pennsylvania. In 2012 Massachusetts voters blocked a right to die act with 51% against the act and 49% in favor. In early 2014, the New Hampshire House of Representatives rejected a bill that would allow such a law. Legislators in Colorado plan to introduce a bill in the 2015 session that would make physician assisted suicide legal.

There are many arguments both for and against laws allowing physician assisted suicide. However, regardless of opinions, it cannot be ignored that it is a hot topic and there will continue to be legislation throughout this coming year regarding the subject. Join us for a Brainy Brunch in December of 2015 to take a closer look at physician assisted suicide and the most recent news surrounding the topic.


1. Death with Dignity Across the U.S. Updated November 13, 2014. http://www.deathwithdignity.org/advocates/national. Accessed December 20, 2014.

2. Eckholm E. New Mexico Judge Affirms Right to ‘Aid in Dying.’ The New York Times. January 13, 2014. http://www.nytimes.com/2014/01/14/us/newmexico-judge-afirms-- right-to-aid-in-dying.html?module=Search&mabReward=relbias%3Ar&_r=0. Accessed December 20, 2014.

3. Kane, L. Medscape Ethics Report 2014, Part 1: Life, Death, and Pain. December 16, 2014. http://www.medscape.com/features/slideshow/public/ethics2014-part1. Accessed December 20, 2014. 

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