Press Releases

End-Stage Respiratory Disease

Fri, 13 Sep 2024 15:15:09 GMT

End-Stage Respiratory Disease

According to World Health Organization, chronic obstructive pulmonary disease (COPD) is now the third leading cause of death globally, and chronic lower respiratory disease is the sixth leading cause of death in the U.S. (2022 Centers for Disease Control). Chronic respiratory diseases are comprised of conditions that affect the respiratory tract and lungs, and the burden on the economy is comparable to lung cancer. These respiratory conditions are both progressive and irreversible. We often think of COPD or lung cancer in isolation, but respiratory decline is also an end-stage sign with many predisposing factors and, fortunately, the symptoms are easily identified and treated with comfort medications.

Respiratory failure can be acute or chronic in nature. Physical signs of respiratory failure include dyspnea, nasal congestion, and/or cyanosis (blue skin, lips or nail beds). The most common types include hypoxemia (decreased oxygen in the blood) and hypercapnia failure (increased carbon dioxide in the blood). A simple pulse oximeter is helpful in monitoring blood oxygen levels on a daily basis. The chronic lung disease trajectory is similar to heart disease. The chronic lung disease trajectory is characterized by exacerbations, treatments (bronchodilators, antibiotics, steroids and/or oxygen), and recovery. While in contrast, the lung cancer trajectory is shorter with rapid deterioration. Both trajectories offer opportunities for symptom management and improvements in patients’ quality of life.

Chronic respiratory diseases include, but are not limited to, COPD, lung cancer, interstitial lung disease, pulmonary hypertension, asthma, and pulmonary inflammation/infections. Below are the prevalent symptoms for end-stage lung disease patients, along with the standard medications to have available for comfort, when appropriate.

Sample Respiratory Toolkit

The COMFORT acronym lists several strategies to help manage acute shortness of breath (dyspnea) attacks:

C - Call for help

O - Observe and treat possible causes

M - Medicate with prescribed rescue medications
F - Fan directed at the face

O - Oxygen therapy, if indicated

R - Relaxation techniques, per patient preference

T - Timing; timely assessment of each intervention above

To optimize shortness of breath management as a patient declines, it’s often best practice to discontinue metered-dose and dry-powder inhalers that become too difficult to coordinate, and require manual dexterity and deep inhalation to achieve their desired results. Inhalers are designed to provide a thirty-day supply, which is often costly and makes the dosing difficult to titrate. When inhalers are not adequately helping with symptoms, additional medications can be added which leads to duplicate therapies and an increased risk for adverse effects.

The preferred medication substitutions for these inhalers include the following:

Albuterol, a short-acting beta2-adrenergic agonist (SABA) and Ipratropium, a short-acting anticholinergic (Antimuscarinic) agent
Albuterol and ipratropium solutions for nebulization (individual or in combination) are the preferred commercially available formulations.
Oral corticosteroids, which include: Prednisone or Dexamethasone (preferred with clinically significant fluid retention)

The below tables list single and multiple medication ingredient inhalers, their mechanisms of action and the preferred cost-effective and clinically-appropriate substitutions.

As hospice clinicians, we know all too well that it can be difficult to transition away from a medication or inhaler that has been helpful in the past. The BUILD Model provides a simple, yet effective framework for having important end-of-life conversations surrounding medication appropriateness and goals of care.

Below are a few helpful questions that can make this conversation a bit easier:

“It seems you are having some difficulty using your inhalers. As your disease progresses it may be useful to make some adjustments to your medications. What worked before may not work as well for you now. Would you like to talk about making your medication routine a little less complicated?”
“It sounds like it’s hard for you to make a decision about stopping your inhaler. Can I share what my experiences and observations have been?”
Before I visit next week, I’ll give your doctor an update and get her input. She might suggest stopping the inhalers and using a nebulizer. Are you willing to give it a try?”

End-stage respiratory disease can be challenging to treat. It’s important to anticipate the patient’s symptoms and have your ‘toolkit’ in place. Meet the patient/family where they are, provide guidance and outline the potential

References

Jadhav U, Bhanushali J, Sindhu A, et al. (December 16, 2023) Navigating Compassion: A Comprehensive Review of Palliative Care in Respiratory Medicine. Cureus 15(12): e50613. DOI 10.7759/cureus.50613

Diseases & Conditions: Respiratory Failure. Cleveland Clinic. [Online] Available from: https://my.clevelandclinic.org/health/diseases/24835-respiratory-failure.

Bourke SJ and Peel ET. Palliative care of chronic progressive lung disease. Clinical Medicine 2014 Vol 14, No 1: 79-82.

De Oliverira EP and Medeiros PJ. Palliative care in pulmonary medicine. J Bras Pneumol. 2020;46(3):e20190280.

Gupta N, Garg R et al. Palliative Care for Patients with Nonmalignant Respiratory Disease. Indian J Palliat Care 2017;23:341-6.

National Hospice and Palliative Care Organization. Deprescribing Toolkit Version 1.0. [Online} Available from: https://www.nhpco.org/wp-content/uploads/NHPCO_Deprescribing_Toolkit.pdf .

Collier KS, Kimbrel JM, Protus BM. Medication appropriateness at end of life: a new tool for balancing medicine and communication for optimal outcomes--the BUILD model. Home Healthc Nurse 2013;31(9):518-524. Available from: https://journals.lww.com/homehealthcarenurseonline/Fulltext/2013/10000/Medication_Appropriateness_at_End_of_ Life A_New.10.aspx Accessed August 20, 2020.

Oropharyngeal Considerations at End of Life

Wed, 20 Mar 2024 19:50:44 GMT

Oropharyngeal Considerations at End of Life

Mouth pain and associated symptoms can be debilitating and affect a patient’s quality of life. The head and neck is

divided into three areas: the nasopharynx, the oropharynx and the laryngopharynx. Oropharynx is derived from the Latin

ōs, -or mouth plus pharynx. The oropharynx is located behind the mouth, below the soft palate and above the hyoid

bone, a u-shaped bone that supports the tongue. This is the area where both food and inhaled air pass through and

disruption of this area can lead to uncomfortable complications.

Normal bodily processes that occur at end of life can lend themselves to oral issues. These include cachexia (wasting),

dehydration, mouth vs. nose breathing, decrease in saliva production, and drying out of the mouth that can lead to

bleeding, inflammation, and even thrush. Psychological and emotional issues such as anxiety, depression, fatigue,

embarrassment, decreased social interaction, and even the physical inability to communicate can hinder the proactive

treatment of mouth-related symptoms. It is helpful to include mouth care related questions in the admission

assessment and simply ask if the patient’s mouth is comfortable to start. Often, mouth care, adjustment of oral

appliances, and/or saliva replacement can proactively prevent complications from occurring. The Kayser-Jones Brief Oral

Health Status Examination is a helpful assessment tool if you suspect mouth issues:

Mouth care is essential to prevent further oral issues as the patient approaches end of life. Below are some tips for

general mouth care and when the patient’s prognosis is days to hours:

Oropharyngeal issues can lead to both physical and psychological symptoms at end of life. Early assessment for

mouth issues and good oral hygiene are often the key to prevention of mouth complications. It is best to start with a

medication review and then topical medications to avoid systemic medications with potentially additive side effects.

References:

Sandvik, R.K.N., Husebo, B.S., Selbaek, G. et al. Oral symptoms in dying nursing home patients. Results from the prospective REDIC study. BMC Oral Health 24,

129 (2024). https://doi.org/10.1186/s12903-024-03901-x.

Venkatasalu MR, Murang ZR, Ramasamy DTR, Dhaliwal JS. Oral health problems among palliative and terminally ill patients: an integrated systematic

review. BMC Oral Health. 2020;20(1):79. Published 2020 Mar 18. doi:10.1186/s12903-020-01075-w.

Christmas C and Rogus-Pulia N. Swallowing disorders and aspiration in palliative care: Assessment and strategies for management. UpToDate. Available Online

with Subscription from: https://www.uptodate.com/contents/swallowing-disorders-and-aspiration-in-palliative-care-assessment-and-strategies-for-

management/print?search=oropharyngeal%20dysphagia&topicRef=2237&source=see_link.

Treister NS, Villa A and Thompson L. Palliative care: Overview of mouth care at the end of life. UpToDate. Available Online with Subscription from:

https://www.uptodate.com/contents/palliative-care-overview-of-mouth-care-at-the-end-of-life?source=history_widget#H75093682.

Kreckel P. What Your Dentist Wishes Patients Knew: An Oral Care Primer for Pharmacy Practice. PharmCon Free CE. [Online] Available with subscription from:

https://myportal.freece.com/course/details/cf48959d-419d-451f-9f36-676e453aab63/7370b168-65b7-4ea4-9d17-667f1ab8e0aa/2c5041db-ab50-4f56-91d7-

a53957727690.

Rademacher WMH, Aziz Y, Hielema A, et al. Oral adverse effects of drugs: Taste disorders. Oral Dis. 2020;26(1):213-223. doi:10.1111/odi.13199

Treatment of Insomnia at End of Life

Wed, 20 Mar 2024 16:38:19 GMT

Treatment of Insomnia at End of Life

Insomnia is defined as issues falling asleep or staying asleep, frequent nighttime awakenings with trouble returning to sleep despite best efforts for proper sleep environment, and adequate opportunity to sleep. It has detrimental effects on mood, normal daytime functioning, and alertness. Types of insomnia are based on symptom duration and include episodic (symptoms for at least one month but less than 3 months), recurrent (two or more episodes in a year), and persistent (lasting more than 3 months).

Causes of insomnia include the following:

Lifestyle : Shift work, “night owl” personality, frequent napping, weeknight/weekend/routines

‘Activating’ Medications: Antidepressants, diuretics, nebulizers/theophylline, decongestants, corticosteroids, anticonvulsants, thyroid supplements

Comorbid Conditions : Anxiety, uncontrolled pain, infections, GERD, breathing issues, restless legs syndrome (RLS)

Environmental: Noise levels, partner snoring, recent move/travel

The insomnia cycle can be an endless loop if a timely intervention does not occur. The stress of clock watching, tossing/turning in bed, hitting the snooze button, and taking lengthy naps during the day can lead to the same trouble sleeping the next night. A differential diagnosis is often necessary to determine and treat the cause of sleeping issues. All of these conditions listed here and more can lead to insomnia:

Narcolepsy : Excessive daytime sleepiness with sudden muscle weakness

Sleep apnea : Brief periods where breathing stops and starts that result in sleep interruption and daytime drowsiness; must wear appliances to help correct breathing

RLS : Painful sensations in lower legs that are relieved by movement and can make it hard to fall asleep/relax

Substance Abuse : Opioids and alcohol can greatly affect sleep

Depression : Ruminating thoughts/anxiety

Insomnia Treatment Strategies

Insomnia treatment requires a multifaceted approach and can include lifestyle modifications, cognitive behavioral therapy, and/or medications (over-the-counter (OTC) or prescription).

Lifestyle Modifications can be made to adjust poor habits, sleep environment, and/or the patient’s nighttime routine. It’s recommended by experts to get outside in the daylight, limit alcohol and caffeine intake, avoid eating for up to 3 hours prior to sleep, and limit the bedroom to sleep only (avoid use of phones/tablets). Create an environment that is conducive to sleep by choosing a comfortable mattress, pillows/bedding, keep the room at a comfortable temperature, block out light and noise and utilize scents that are light and relaxing. It also is best to have a routine to set yourself up for a good night’s rest. Keep to a consistent sleep/wake schedule, relax for thirty minutes prior to sleep, dim the lights and, most importantly, if you are unable to sleep, get up and try again later.

Cognitive behavioral therapy (CBT) focuses on negative attitudes, dysfunctional behaviors, and beliefs that lead to insomnia. It may be more effective than medications, with less adverse effects reported. Treatments include sleep restriction, stimulus control, keeping a sleep diary, relaxation therapy, and sleep hygiene education. Barriers to use of CBT are the intensity of the therapy for a hospice/palliative care patient and insufficient providers with required expertise.

Over-the-counter (OTC) sleep aids such as diphenhydramine and doxylamine may be beneficial for the short-term treatment of insomnia, but are not recommended for longer-term use due to anti-cholinergic side effects such as confusion and urinary retention, and possible exacerbation of conditions such as benign prostatic hyperplasia (BPH), asthma, cardiovascular disease, benign prostatic hyperplasia (BPH), and glaucoma.

OTC Dietary supplements have gained popularity including Melatonin. This sleep aid helps to control/reset natural circadian sleep rhythms with a wide dosing range of 0.1 to 5 mg at bedtime. Melatonin is recommended for short-term use only and may be stopped once the patient has noticed sleep improvements (proper sleep rhythms restored).

Prescription classes for insomnia include benzodiazepines (temazepam), hypnotics (zaleplon, zolpidem, eszopiclone) antidepressants (Trazodone, Mirtazapine) and newer classes such as orexin receptor antagonists (Belsomra®). Below are the preferred medications on the preferred drug list for cost and efficacy.

Insomnia can be a challenging symptom to manage at end of life amidst the other factors at play. Consider utilizing lifestyle modifications as first-line, and medications sparingly. With the understanding that medications have their limitations at end of life and as always, keep the patient and family goals of care in mind.

References

Kasbekar R and Ambizas EM. Helping People Manage Insomnia. US Pharm. 2022;47(1):4-12.
Davies A. Sleep problems in advanced disease. Clin Med (Lond). 2019 Jul;19(4):302-305. doi: 10.7861/clinmedicine.19-4-302. PMID: 31308108; PMCID: PMC6752246.
Corvino M and Swanson C. Overview of Insomnia Pharmacotherapy. CorConsult Rx Podcast. [Online] Available by subscription from: https://myportal.freece.com/course/details/9a2f8e7c-80bd-4cbe-b7d9-40d234194246/446c48da-f681-4bbf-809c-97336a96ec23/2c5041db-ab50-4f56-91d7-a53957727690.
Okun,M.L., Kravitz,H.M., Sowers,M.F., Moul,D.E., Buysse,D.J., & Hall,M. (2009). Psychometric evaluation of the Insomnia Symptom Questionnaire: A self-report measure to identify chronic insomnia. Journal of Clinical Sleep Medicine, 5(1), 41-51. [Online] Available from: https://sleep.pitt.edu//wp-content/uploads/Study_Instruments_Measures/ISQ-article.pdf.
Wilhelm M. Sleep and Stress: Pharmacist Insights on Non-Prescription Treatment Options. PowerPak. [Online] Available from: https://www.powerpak.com/course/content/122306.
LexiComp. Wolters Kluwer Health, Inc. Riverwoods, IL. Accessed December 2023.
Hospice Medication Utilization Guidelines. ProCare Hospice Care. Insomnia. Available Online with registration from: https://phc.procarerx.com/docs/hugs/Section%20Three%20Symptom%20Management%20Algorithms.pdf.

Fatigue at End of Life

Mon, 04 Sep 2023 22:52:38 GMT

Fatigue is defined as a subjective feeling of tiredness, weakness, or lack of energy that can affect one’s physical,

emotional, and cognitive state.

It is one of the most common, distressing symptoms at end of life – ranking up there with pain and anxiety. Yet fatigue is often under-treated and difficult to diagnose, especially when presented with other symptoms that need attention. In fact, patients and clinicians often perceive fatigue as a symptom to be ‘endured’ rather than addressed and managed appropriately. It is also important to document fatigue in the patient’s chart, as it may be a sign of decline.

Fatigue rarely occurs in isolation. In some cases, the cause might not be so clear. You may run labs to identify potential contributing factors (e.g., anemia, electrolyte imbalance), or use scales or assessment tools to index the severity of the fatigue. This helps distinguish it from other common conditions like depression or delirium.

A thorough assessment of fatigue should include the following:

Complete a thorough history and physical exam (fatigue greater than current activity levels)
Run labs (optional)
Use available scales and assessment tools:
Fatigue Severity Scale (FSS)
Visual Analog Fatigue Scale (VAFS)
Fatigue Assessment Scale (FAS)
Multidimensional Fatigue Inventory (MFI)

Examples available from: https://www.sralab.org/rehabilitation-measures/; https://www.med.upenn.edu/cbti/assets/user-

content/documents/Fatigue%20Assessment%20Scale%20(FAS).pdf

Strategies for Treatment of Fatigue

Non-Pharmacological Interventions

Patient/Family Education: set reasonable goals based on disease trajectory
Modify and prioritize high-energy activities
Exercise (more realistic in palliative care patients)
Aerobic exercise; goal of 20-30 mins/day, 3 times a week (low-to-moderate intensity)
Resistance training may be beneficial
Individualize to patient preferences
Cognitive Behavioral Therapy (CBT):
Most evidence with cancer survivors
Goal: Interrupt and redirect dysfunctional thoughts and behaviors

Pharmacotherapy for Fatigue

Reserved for patients who have either:
Failed non-pharmacological therapies – OR –
Are not candidates for non-pharm therapies
Little to no benefit/efficacy found in literature
Assess the following:
Interaction check and review adverse reactions (Benefit > Risk)
Time to benefit

Three Potential Options:

Psychostimulants

Methylphenidate (Ritalin) - preferred
Dose: 2.5 mg (up to 30 mg) BID - QAM and Qnoon
Efficacy over placebo for improvement in “tiredness” that lasted up to 5 hours in recent study
Modafanil (Provigil) - non-preferred due to cost
Cancer-related fatigue, severe (in patients receiving active treatment) (off-label use): Oral - Initial: 100 mg once daily for 3 days, followed by 200 mg once daily during active treatment
Parkinson disease–related excessive daytime sleepiness (off-label use): Oral - Initial: 100 mg once daily; may increase dose after 1 week to 200 mg/day

2. Corticosteroids

Treat a variety of symptoms at end of life (portmanteau concept)
Several Options:
Prednisone 7.5-10 mg PO QAM; or
Dexamethasone 1-4 mg PO QAM or BID; or
Methylprednisolone 32 mg PO daily
Time to benefit: 1-2 weeks
Possible adverse effects: risk of infection, hyperglycemia, insomnia, muscle weakness and osteoporosis (long term)

3. Antidepressants: promising benefits in randomized controlled trials

Bupropion (Wellbutrin) – preferred; 150 mg PO daily
Time to benefit: 1-4 weeks
Paroxetine (Paxil) – preferred; 20 mg PO daily
Time to benefit: 2-4 weeks

In summary, fatigue is a difficult symptom to recognize and successfully treat. It is recommended to utilize an appropriate fatigue assessment tool, along with a detailed history and physical exam. Always individualize a fatigue treatment plan that best suits the patient and their individual preferences, and monitor closely for efficacy as well as any adverse effects.

References:

Esch AE and Newman S. Clinical Care: How to Identify and Treat Fatigue in Our Patients with Serious Illness. Center to Advance Palliative Care. [Online] Available from: https://www.capc.org/blog/how-to-identify-and-treat-fatigue-in-our-patients-with-serious-illness/.

Reisfield GM, Lowry MF and Wilson, GR. Fast Facts and Concepts #173 Cancer-Related Fatigue. Palliative Care Network of Wisconsin. [Online] Available from: https://www.mypcnow.org/wp-content/uploads/2019/02/FF-173-Cancer-Fatigue.-3rd-Ed.pdf.

Ingham G, Urban K. How Confident Are We at Assessing and Managing Fatigue in Palliative Care Patients? A Multicenter Survey Exploring the Current Attitudes of Palliative Care Professionals. Palliat Med Rep. 2020 May 28;1(1):58-65. doi: 10.1089/pmr.2020.0005. PMID: 34223457; PMCID: PMC8241319.

Henson LA, Maddocks M, Evans C, Davidson M, Hicks S, Higginson IJ. Palliative Care and the Management of Common Distressing Symptoms in Advanced Cancer: Pain, Breathlessness, Nausea and Vomiting, and Fatigue. J Clin Oncol. 2020 Mar 20;38(9):905-914. doi: 10.1200/JCO.19.00470. Epub 2020 Feb 5. PMID: 32023162; PMCID: PMC7082153.

Narayanan V and Koshy C. Fatigue in Cancer: A Review of Literature. Indian J Palliat Care. 2009 Jan-June; 15(1).

Cross LA. Compassion Fatigue in Palliative Care Nursing: A Concept Analysis. J Hosp Palliat Nurs. 2019 Feb;21(1):21-28. doi: 10.1097/NJH.0000000000000477. PMID: 30608916; PMCID: PMC6343956.

Non-Traditional Pain Management

Sun, 03 Sep 2023 20:47:35 GMT

Pain is a common and debilitating symptom experienced in our hospice and palliative care patients.

There are three distinct types of pain, including:

Nociceptive: Localized, consistent pain; tissue damage/ inflammation
Neuropathic: Caused by nerve damage; follows nerve pathways; described as episodic numbness, tingling, burning or stabbing pain
Nociplastic: Centralized and widespread pain syndrome; chronic overlapping type pain conditions (ie fibromyalgia)

Nociplastic pain is a more recently utilized term. The International Association for the Study of Pain (IASP) officially adopted the term in 2018 as a “third mechanistic descriptor” of chronic pain to “more fully characterize the known pathophysiological mechanisms of pain.”

There are several reasons why clinicians and patients or their family members steer toward the non-traditional/alternative medicine route vs. the standard of care for pain management (medications including opioids, NSAIDs or acetaminophen). These reasons include adverse reactions (drowsiness is typically number one, followed by constipation and nausea), safety concerns (fall risk), the fear factor (morphine in particular), lack of efficacy (despite escalating doses), abuse/misuse, and overall patient preference.

There are several therapy types available for non-traditional pain management:

Medication Therapies
If the patient/family is hesitant to try opioids or increase the dose of their current opioid regimen, potential adjuvant medications for neuropathic pain include gabapentin and antidepressants such as amitriptyline, nortriptyline, venlafaxine or pregabalin (Lyrica®). These medications are effective for nerve pain; however, they carry the risk for adverse effects such as drowsiness.

Methadone is an alternative opioid that is long acting and may help with both nociceptive and neuropathic pain due to its distinctive mu opioid agonist activity. Methadone is a synthetic opioid that is in the phenyl-heptylamine class of opioids (separate from morphine), which makes it safe to use with morphine allergies and tolerated better than traditional opioids.

Natural Therapies

Cannabis
Medical Marijuana and Cannabis have a rich and controversial history. The endocannabinoid system within the body regulates the synaptic neurotransmission and is comprised of two cannabinoid receptors, CB1 (brain and CNS) and CB2 (peripheral organs/immune system). CBI receptors have a similar neurochemical and pharmacological characteristics to opioid receptors and cannabis’ analgesic effects may be mediated at the spinal cord. It has been proven effective in refractory neuropathic pain and pain associated with Multiple Sclerosis and various cancers. In studies, cannabis is significantly better than placebo, but comparable to codeine. The greatest benefits may be seen in neuropathic pain and as an adjunct to other long-acting pain regimens. Cannabis products are available in a variety of products and routes of administration, inhalation and oral routes are the most commonly used.

There are several notable adverse effects of cannabis use including, but not limited to: euphoria, sedation, psychosis, memory loss, hallucinations, appetite changes (could be a positive), sleep disturbances and dry mouth. Even though cannabis has become more popular in the last few years, it is still a Schedule I controlled substance (CI) federally. Due to this CI status, it cannot be prescribed legally by a physician and is subject to state-specific regulations at this time. To view your state-specific cannabis laws, visit the National Conference of State Legislature (NCSL) website at https://www.ncsl.org/health/state-medical-cannabis-laws. Keeping your state-specific laws in mind, it is best as a hospice clinician to document that your patient intends to use cannabis and provide them with evidenced-based resources to encourage safe use.

Aromatherapy

Essential oils are FDA classified as “cosmetics”
Knowledge is key to proper use for patient, family, and nurse
Safety concerns: toxicity (oral or inhaled), chemical burns, flammability
Potential benefits for hospice/palliative care
Pain Management
Nausea/Vomiting
Anxiety/Stress
Insomnia

Integrative Therapies

Meditation
Most studied technique = Mindfulness-based stress reduction (MBSR)
Generally safe with no reported adverse effects
Mental activity can influence physiologic function
Not specifically helpful for pain, but showed promise for emotional wellbeing, anxiety, depression, and stress
Massage Therapy
Swedish massage using specific strokes used most often in cancer patients
Also reflexology, deep tissue massage, shiatsu
Studies show modest improvement in pain scores
Safety concerns (use a trained massage therapist): Avoid pressure around tumor or bone metastases sites; implanted pumps, areas of wound or skin breakdown, sensitive skin after radiation
Acupuncture
Founded from Traditional Chinese Medicine practices
Method: Use of filiform needles inserted on body in specific areas and stimulated with manual manipulation (twist, pull, or push), heat or electrical pulses
Systematic reviews show a significant reduction in pain intensity of acute/chronic low back pain vs. placebo
Cancer pain: equivalent or superior to oral pain medications
Safety concerns: Pain/bleeding during needling

Based on the best available evidence, refractory pain is best managed with a combination of pharmacological and non-pharmacological type therapies. Adverse reactions and side effects can limit use of opioid or adjuvants for pain management. It is important to respect individual patient values and find that delicate balance between traditional medicine and complementary methods to achieve patient-centered care at end of life.

References

Zeng YS, Wang C, Ward KE, Hume AL. Complementary and Alternative Medicine in Hospice and Palliative Care: A Systematic Review. J

Pain Symptom Manage. 2018 Nov;56(5):781-794.e4. doi: 10.1016/j.jpainsymman.2018.07.016. Epub 2018 Aug 2. PMID: 30076965.

Moaleji, N. and Pangarkar, S. (2016, April). Oral Methadone Dosing Recommendations for the Treatment of Chronic Pain. Retrieved

from:

https://www.pbm.va.gov/PBM/clinicalguidance/clinicalrecommendations/Methadone_Dosing_Recommendations_for_the_Treatment_o

f_Chronic_Pain_July_2016.pdf

Habershaw, A. (2012, May). Methadone and QTc Prolongation. Retrieved from

https://www.urmc.rochester.edu/medialibraries/urmcmedia/medicine/palliativecare/patientcare/documents/methadoneandqtcprolong

ation.pdf

Reddy S, Hui D, El Osta B, et al. The Effect of Oral Methadone on the QTc Interval in Advanced Cancer Patients: A Prospective Pilot Study.

J Palliative Med. 2010;13:33-38.

Krantz MJ, Martin J, Stimmel B, et al. QTc Interval Screening in Methadone Treatment. Ann Intern Med. 2009;150:387-395.

Wong, E. (2013, January). A review of common methods to convert morphine to methadone. Retrieved from

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3715153/

Osvaldo, Jose. (2015, March). Revisiting methadone: pharmacokinetics, pharmacodynamics and clinical indications. Retrieved from

http://www.scielo.br/scielo.php?script=sci_arttext&pid=S1806-00132015000100060

Gagnon B, Almahrezi A, Schreier G. Methadone in the treatment of neuropathic pain. Pain Res Manag. 2003;8:149-154.

Symptom Management of End Stage Heart Disease

Tue, 01 Aug 2023 16:51:08 GMT

By Meri Madison, PharmD, RP

End-stage heart disease is not only a debilitating condition, but is largely prevalent in hospice/palliative care and accounts for upwards of 20% of healthcare-related spending. It is estimated that by 2030, heart failure prevalence will increase by an astounding 46%.

Common causes of heart failure include, but are not limited to: genetic cardiomyopathies, amyloidosis, cardiotoxicity with cancer treatments, substance abuse, tachycardia, stress-induced cardiomyopathy, myocarditis, autoimmune, sarcoidosis, iron overload, thyroid disease, endocrine metabolic and/or nutritional deficiencies. To make symptom management even more complicated, greater than 85% of patients have two or more chronic conditions on top of their heart condition (ex: chronic kidney disease, diabetes, morbid obesity, anemia, etc.)

Unlike many cancers, which are characterized by a steep, predictable decline over the last few months of life, heart failure is characterized by an unpredictable trajectory of decompensations and improvements, with a more subtle decline over time. This can make it difficult to determine when a heart failure patient may definitively qualify for palliative or hospice care. However, this type of trajectory emphasizes the importance of providing proactive plans for symptom relief as life-prolonging care is discontinued, and harm of treatment outweighs its benefits.

Below are some possible strategies and a toolkit to equip hospice clinicians to best manage patients with heart disease to both minimize symptoms and maximize their quality of life.

**See diuretic resistance strategies below; reserve thiazide diuretics thiazides for patients that are not responsive to moderate-high-dose loop diuretics to minimize risk of electrolyte abnormalities.

Patient Monitoring
Once the patient has started one of the medications above, monitor at each visit for changes in condition and/or emergent symptoms based on their mechanism of action (ex: Metoprolol - record BP/HR at each visit; Furosemide - document degree of edema). Adjust up or down as necessary to achieve symptom relief without tipping the scale towards unnecessary side effects.

Combating Diuretic Resistance

The newer agents to treat heart failure and related symptoms (Angiotensin neprilysin inhibitor/ Angiotensin receptor blocker; Entresto and Sodium glucose-2 transport inhibitors; Farxiga/”flozins”) are difficult to titrate/taper, and are non-preferred and cost prohibitive at this time.

Medication management for end-stage heart disease remains a mainstay of symptom control and these medications are appropriate to continue as long as the benefits still outweigh any risks. As with any life-limiting illness, education for the patient, family members and hospice clinicians is key to keeping the patient comfortable in their last days.

References

Steinberg L, White M, et al. Approach to advanced heart failure at the end of life. Can Fam Physician 2017;63:674-80.

Adler et al. Palliative Care in the Treatment of Advanced Heart Failure. Volume 120, Issue 25, 22 December 2009; Pages 2597-2606. https://doi.org/10.1161/CIRCULATIONAHA.109.869123

Reisfield GM, Wilson GR. Fast Facts and Concepts #144: Palliative Care Issues in Heart Failure. [Online] Available from: https://www.mypcnow.org/fast-fact/palliative-care-issues-in-heart-failure/

Sarbacker GB and Wilder AG. Heart Failure Guidelines: Introduction to the New Agents. US Pharm. 2018;43(2):22-26. [Online] Available from: https://stage.uspharmacist.com/article/heart-failure-guidelines-introduction-to-the-new-agents

Strategies for Fall Prevention in Hospice/Palliative Care

Mon, 12 Jun 2023 22:38:12 GMT

By 2030, 1 in 5 Americans will be aged 65 and older and we can anticipate 52 million falls and 12 million fall injuries.

Falls occur in virtually all healthcare settings and can have devastating consequences, including serious injury and subsequent falls. The risk for falls increases exponentially with age, and greater than 1 out of every 4 older adults (65 years and up) falls each year. If more emphasis is not placed on the reduction of fall risks, the number of falls and fall injuries will keep rising. By 2030, 1 in 5 Americans will be aged 65 and older and we can anticipate 52 million falls and 12 million fall injuries.

The Joint Commission has recognized fall prevention as one of the National Patient Safety Goals®, effective July

2023 for home care programs. The Elements of Performance are listed below:

Assess the patient’s risk for falls
Implement interventions to reduce falls based on the patient’s assessed risk
Educate staff on the fall reduction program in timeframes determined by the organization
Educate the patient and, as needed, the family on any individualized fall reduction strategies

It is recommended that a fall risk assessment include a comprehensive look at past medical history (including all fall events), a review of the patient’s medication list and substance use, and a physical exam with mobility check for gait and balance when ambulating. Next steps for safety could include an assessment of current walking aids, the potential for additional walking aids/protective devices, and an environmental assessment (loose rugs, narrow walkways, etc.). When asking about the patient’s fall history, ask the tough questions of the patient and/or caregivers:

Have you experienced fall(s) over the past year?
Can you describe the last fall you had?
What caused the fall to happen?

For the medication review, be on the lookout for the following:

>5 medications (routine/PRN) increases fall risk = Polypharmacy
# of doses/day
Any recent medication changes including:
Addition
Discontinuation
Adjustment
Adverse Effects/Reactions

Strategies for Fall Prevention in Hospice/Palliative Care (continued)
As part of the medication review, use the SAFE approach below; identify any medications that your patient takes that may increase the risk for falls and discuss possibly tapering down or discontinuing to mitigate the risk.

Potential Interventions to Prevent Falls for Hospice Patients:

Fall prevention education (family, patient, IDT, facility staff)
Recommend assistive devices (walker, wheelchair, etc.)
Environmental changes (eliminate floor clutter and floor rugs, add grab bars in shower, etc.)
Supervision/assistance (hospice aides at greater frequency)
Medication adjustments (decreased dose, taper and/or discontinuation)
Exercise programs/balance training, if able to tolerate

Recommended Fall Prevention Resources:

ASCP-NCOA Falls Risk Reduction Toolkit: https://www.ascp.com/general/custom.asp?page=fallstoolkit
STEADI: Stopping Elderly Accidents, Deaths, and Injuries: https://www.cdc.gov/steadi/index .ht ml

Summary

When it comes to fall prevention in the hospice and palliative care setting, focus on taking proactive, multifactorial steps to help keep your patients safe. Education is key to the success of your fall prevention program. Involve the interdisciplinary team at every step in the process and document all steps and strides taken to ensure everyone is on the same page.

References

Centers for Disease Control and Prevention. STEADI materials for healthcare providers. http://www.cdc.gov/steadi/materials.html. Accessed May 5, 2016.

Gray J. Protecting hospice patients: A new look at falls prevention. Am J Hosp Palliat Care. 2007 Jun-Jul;24(3):242-7. doi: 10.1177/ 1049909106298721. PMID: 17601851.

Vieira ER, Palmer RC, Chaves PH. Prevention of falls in older people living in the community. BMJ. 2016 Apr 28;353:i1419. doi: 10.1136/ bmj.i1419. PMID: 27125497.

Clackum, S. Falls and falls risk inducing drugs (FRIDs). [Online] Available through subscription from: https://learning.ascp.com/diweb/catalog/item/id/9247065/sid/159926393/q/q=falls&c=305.

The Joint Commission. Home Care: 2023 National Patient Safety Goals effective July 1, 2023. [Online] Available from: https://www.jointcommission.org/standards/national-patient-safety-goals/home-care-national-patient-safety-goals/.

American Society of Consultant Pharmacists (ASCP). ASCP-NCOA Falls Risk Reduction Toolkit. [Online] Available from: https://www.ascp.com/general/custom.asp?page=fallstoolkit.

Moncada LVV, Mire LG. Preventing Falls in Older P ersons. Am Fam Physician. 2017 Aug 15;96(4):240-247. PMID: 28925664.

Management of Oral Secretions and Congestion at End of Life

Sun, 05 Mar 2023 22:12:05 GMT

The presence of noisy respirations due to excessive secretions (also known as “gurgling” or “rattling”) at end of life predict a prognosis of days to weeks and can be alarming to family members.

The presence of noisy respirations due to excessive secretions (also known as “gurgling” or “rattling”) at end of life predict a prognosis of days to weeks and can be alarming to family members. Typically, patients do not require treatment for terminal secretions because it is not bothersome to them. However, the noises are bothersome to the caregivers, and their number one goal is ensure the comfort of their loved one in their last days.

Mucous is composed of 95% water, glycoproteins, proteoglycans, and lipids. In normal circumstances, we produce about 1.5 quarts of mucous per day, pushed to the back of the throat by tiny cilia and swallowed (this will occur approximately 20 times while you read this article). Mucous has two functions: it keeps the nasal cavity and air entering the lungs moist to prevent dryness, and it acts as a filter for your lungs. A healthy patient is able to effectively clear these oral secretions. However, as a patient declines, they lose the ability to swallow effectively, often due to loss of consciousness. The secretions then pool in the throat and the oscillation (movement) of air causes the noise.

There are two secretory subtypes, Salivary and Bronchial.

Certain contributing factors can increase or exacerbate secretions/congestion when a patient is admitted to hospice. These include: neurological disorders; use of certain medications (clozapine, clobazam, and/or doxycycline); cancer of the mouth, tongue, larynx, or esophagus; respiratory edema or infection; and also pre-existing gastroesophageal issues such as dysmotility or gastroesophageal reflux disorder (GERD).

The best way to tackle end-stage secretions is to follow these three steps:

Determine the type of the secretion
Start with non-pharmacological options first
Add on a preferred medication based on patient-specific factors

Non-Pharmacological Interventions

Re-positioning the patient on their side can facilitate drainage
Reducing fluid intake or intravenous fluid administration
Maintaining adequate oral hygiene
Gentle suctioning may be used; this may be ineffective when fluids are beyond reach, and can be disturbing to both the patient and surrounding caregivers
Communication with family and caregivers to explain terminal secretions

Pharmacological Interventions

Drug selection should be individualized
Selecting which medication to use should be based on patient factors (such as age, diagnosis, prognosis) as well as drug factors (onset of action, route of administration, cost)
Manage symptoms of underlying pathology (e.g. CHF, lung disease)
Consider an antibiotic, if appropriate, based on prognosis, allergies, patient/family goals of care

Oral/Sublingual Treatment Options

Treatment Options Using Alternative Routes

Utilize anticholinergic medications with caution, as the risk of side effects may outweigh the benefits of their use to lessen secretions. Common anticholinergic side effects include: blurry vision, dry mouth, confusion, tachycardia, urinary retention, skin flushing and constipation. Atropine and scopolamine are both tertiary amines and readily cross the blood-brain barrier (BBB), which may lead to increased CNS side effects such as confusion, delirium, hallucinations, sedation, and agitation. Hyoscyamine and glycopyrrolate are both quaternary amines and do not cross BBB and, therefore, less likely to cause CNS side effects.

Scopolamine is available as a patch and has issues with unpredictable absorption, as well as difficulties with titration. It can take up to 6-12 hours for the desired effects and, in some studies, up to three patches may be applied to aid in secretion management.

Hyoscyamine is the anticholinergic of choice, 0.125mg SL Q4H prn secretions, due to lower cost and availability as a sublingual tablet. Recommend monitoring patients for adverse effects and avoid use with bronchial secretions, as use can create a mucous plug and worsen secretions.

When chest congestion is suspected vs. end-stage secretions, guaifenesin (Mucinex) may be utilized as an expectorant to help loosen and expel thicker secretions. Typical dosing is 600-1200mg PO BID for the extended release tablet, and 20mL PO Q4H prn for congestion for the liquid. Keep in mind that guaifenesin should be taken with plenty of water and can cause nausea as a side effect.

Alternative Treatments for Chest Congestion:

Nebulized solutions:
Bronchodilator: Albuterol 0.083% 1 unit dose INH Q4H prn congestion
Hypertonic saline 3% via nebulizer (use albuterol first, then saline)
Alternative Bronchodilator: Theophylline (use with caution due to adverse reactions)
Antibiotics: If indicated and in line with goals of care (limited due to culture/sensitivity results)
N-acetylcysteine (Mucomyst): Reserve for most refractory cases
$$$, odorous, risk of bronchospasm (use with bronchodilator, if possible)

End-stage secretions are commonly seen in hospice and palliative care patients, and assessment is key to successfully treating this bothersome symptom. It is important to determine if they are truly respiratory secretions or congestion related to an underlying respiratory issue, such as infection or a COPD exacerbation. There are several options available to treat secretions and, as always, it is important to consider risk vs. benefit, especially prior to starting an anticholinergic medication with a well-known side effect profile. Monitor the patient closely and be proactive with medications on hand in the care pack or on standing orders to help keep the patient comfortable 24/7/365.

References:

Hsin G and Hallenbeck J. Fast Facts and Concepts #158. Respiratory Secretion Management. Palliative Care Network of Wisconsin. [Online] Available from: https://www.mypcnow.org/fast-fact/respiratory-secretion-management .
Bickel K, Kareem L et. Al. Fast Facts and Concepts #109. Death Rattle and Oral Secretions. Palliative Care Network of Wisconsin. [Online] Available from: https://www.mypcnow.org/fast-fact/death-rattle-and-oral-secretions/ .
Kintzel PE, Chase SL et. Al. Anticholinergic medications for managing noisy respirations in adult hospice patients. Am J Health-Syst Pharm. 2009; 66:458-64.
Morrison L, Innes S. Oscillating devices for airway clearance in people with cystic fibrosis. Cochrane Database Syst Rev. 2017 May 4;5(5):CD006842. doi: 10.1002/14651858.CD006842.pub4. Update in: Cochrane Database Syst Rev. 2020 Apr 30;4:CD006842. PMID: 28471492; PMCID: PMC6481377.
Back IN, Jenkins K, Blower A, Beckhelling J. A study comparing hyoscine hydrobromide and glycopyrrolate in the treatment of death rattle. Palliat Med 2001; 15: 329-336.
Bennett M, Lucas V, Brennan M, et al. Using anti-muscarinic drugs in the management of death rattle; evidence based guidelines for palliative care. Palliat Med 2002; 16:369-374.

The 12 Clinical Pearls of Symptom Management

Wed, 15 Feb 2023 22:49:53 GMT

When managing symptoms at end of life, it can be a struggle to find the most appropriate medications.

Below are several guiding principles for symptom management that help keep the focus on the patient and their comfort as their goals of care transition from curative to comfort care.

Choose medications that are both therapeutically appropriate and cost effective:

Therapeutically appropriate with regard to routes of administration, renal/hepatic impairment, flexibility with “as needed” (PRN) dosing
Cost effective with regard to generic vs. brand selection, routes of administration selection, and goals of care - minimization of pill burden

2. Examine medication route of administration:

Assess the patient’s current and future PO status to anticipate needs
Utilize tablets first line, then liquids if necessary
Immediate release (IR) tablets preferred over extended release (ER, SR, XR)

3. Choose one medication to treat multiple symptoms

Example: Prednisone or dexamethasone for pain, inflammation, breathing, and appetite

4. For pain management and breathing, morphine is typically the gold standard unless there is a contraindication, such as a

severe allergy or renal impairment.

Morphine may be utilized acutely during the final days of life (up to approximately 7 days), even in patients with severe renal impairment, without anticipation of significant adverse effects

5. For nausea and/or vomiting (N/V), prochlorperazine or promethazine are gold standard treatments:

Haloperidol is traditionally classified as anti-psychotic but is also listed off-label as an anti-emetic
Ondansetron is effective for chemotherapy- or radiation-induced N/V

- The oral disintegrating tablet (ODT) must be swallowed and not given under the tongue (SL)

6. For constipation, prophylaxis is the BEST treatment:

Plain Senna® (sennosides) 1-2 tabs PO QHS-BID (max 4 tabs po bid)

If the rectum is full and the stool is hard: Fleets enema OR a glycerin suppository daily if no BM in the last 24 hours
If the rectum is full and the stool is soft: Fleets enema OR bisacodyl (Dulcolax®) 10 mg supp rectally daily if no BM in the last 24 hours; continue or add Senna 1-2tabs po qHS-bid

7. For congestion, inhalers are expensive and most likely no longer effective

Preferred substitution: Albuterol/ipratropium nebs routine, +/- oral steroid

8. For terminal secretions, Hyoscyamine (Levsin) 0.125 mg SL Q4H prn secretions preferred over Atropine ophthalmic solution

9. Initiate deprescribing upon admission. Review the patient’s medication list and discontinue medications that are no longer

necessary for symptom management.

10. If Insulin is still necessary, avoid short-acting insulins in favor of long-acting insulin to avoid hypoglycemia, uncomfortable

needle sticks, and confusing regimens for caregivers

11. Discontinue multivitamins and supplements if possible. The risk of GI upset, constipation/diarrhea if declining appetite

outweigh any benefits.

12. General rule for tapering medications: If patient no longer able to swallow the pill, then OK to discontinue with taper.

Make an attempt to taper, if possible, OR switch to another medication that can be crushed or given sublingually instead

This document is for informational and educational purposes only and is not a substitute for medical advice, diagnosis, or treatment provided by a qualified health care provider. All information contained in this document is protected by copyright and remains the property of ProCare HospiceCare. All rights reserved.

Renal Impairment at End of Life: Dosing Implications for Opioids, Non-Steroidal Anti-Inflammatory Drugs (NSAIDs), and Antibiotics

Fri, 21 Oct 2022 17:44:59 GMT

Renal impairment is relatively common in both the elderly and hospice patients, and it can affect the way medications act in the body in several ways. Most commonly, it results in decreased clearance of renally-excreted medications, leading to accumulation of the drug and/or its metabolites and subsequent adverse or toxic effects. The absorption of oral medications may be reduced in patients with renal impairment due to increased gastric pH and gut wall edema. Uremia caused by renal impairment can increase sensitivity to medications that act on the central nervous system (CNS), as well as increase the risk of hyperkalemia due to potassium-sparing drugs. In addition, uremia can enhance the potential for NSAID-induced edema or GI bleeding. Renal impairment can also lead to edema or ascites, cachexia, dehydration, decreased albumin levels and binding capacity, and decreased tissue binding, all of which can impact the effects of medications.

To compensate for these renal impairment-induced changes in drug disposition, the typical actions taken regarding medication administration are to decrease the dose, increase the dosing interval, or a combination of the two. The action that would be recommended depends on the drug and its specific characteristics. There are many medications that require dose adjustment in renal impairment, but here we’ll be discussing just those that are most often seen in hospice. The goal is to make you aware of these common medications (and categories) that often need dose adjustment so they trigger a mental alert for possible follow-up if they are ordered for your patients with decreased renal function.

Opioids: Many opioids can accumulate in renal impairment as the parent drug and/or metabolites.

Tramadol has a maximum daily dose in all patients, but in patients with a creatinine clearance (CrCL) less than 30 mL/minute, this maximum dose is reduced to 200 mg per day and the dosing interval should be extended to every 12 hours.
Morphine renal dose reductions start with a CrCL less than 60 mL/minute, with possible extension of the dosing interval at this point as well. It is typically recommended to start considering alternatives to morphine in patients with a CrCL less than 30 mL/minute, and to avoid it altogether in patients with a CrCL less than 15 mL/minute.
At end of life, the benefits of morphine can sometimes outweigh the risks. Because the presentation of renal accumulation-based adverse effects may be delayed, morphine can be used even in severe renal impairment or renal failure when the prognosis is hours to days, or in dialysis patients when death is imminent.
Typically, oxycodone and hydromorphone are considered preferred alternatives to morphine in patients with significant renal impairment, although they both have metabolites that can accumulate in renal failure. As a result, the dose of oxycodone should be reduced and the dosing interval increased in patients with a CrCL less than 60 mL/minute, and oxycodone extended-release products should usually be avoided in patients with a CrCL less than 30 mL/minute. Hydromorphone dose reduction is also recommended when CrCL is less than 60 mL/minute; further dose reduction and extension of the dosing interval is recommended for hydromorphone when CrCL is less than 30 mL/minute.
Although hydrocodone and its active metabolites may accumulate in renal impairment, there are no dose reductions for hydrocodone/acetaminophen according to the manufacturer’s labeling. Hydrocodone extended-release products (Hysingla ER®, Zohydro ER®) are rarely used in hospice, but dose reductions are recommended in patients with moderate to severe renal impairment.
Methadone and fentanyl patch are considered among the safest opioids in renal impairment because they do not have active metabolites. However, renal impairment can still alter how fentanyl moves in the body, so dose reduction is recommended in patients with a CrCL of 50 mL/minute or less. For methadone, dose reduction is not recommended until very severe renal impairment (CrCL less than 10 mL/minute).
No dose reductions are recommended for buprenorphine at any degree of renal impairment, and it is generally considered safe in this population.

NSAIDs: Examples of NSAIDs that are commonly used in hospice include ibuprofen (Advil®, Motrin®), naproxen (Aleve®), and meloxicam (Mobic®), and as mentioned previously, there are some concerns regarding the use of NSAIDs in renal impairment. According to the Kidney Disease: Improving Global Outcomes (KDIGO) 2012 Clinical Practice Guideline, prolonged therapy with NSAIDs is not recommended if GFR is less than 60 mL/minute/1.73m² , and NSAIDs should typically be avoided in patients with a GFR less than 30 mL/minute/1.73m². As a general rule, NSAIDs should be used at the lowest effective dose for the shortest time possible in patients with renal impairment. In addition, NSAIDs should be avoided in patients with a high risk for developing acute kidney injury (e.g. volume depleted, elderly, and/or taking other nephrotoxic medications), and should be discontinued if acute kidney injury occurs during use.

Antimicrobials: Many antimicrobials require dose reduction and/or extension of the dosing interval in renal impairment. Specific dosing recommendations depend on the antimicrobial in question and the type of infection being treated.

When used for multiple doses, the dose of the antifungal fluconazole (Diflucan®) should be reduced in patients with a CrCL of 50 mL/minute or less.
Examples of antibiotics commonly used in hospice that need dose adjustment include: sulfamethoxazole/trimethoprim (Bactrim®); fluoroquinolone antibiotics, including ciprofloxacin (Cipro®) and levofloxacin (Levaquin®); certain penicillin antibiotics, such as amoxicillin and amoxicillin/clavulanate (Augmentin®); and some cephalosporins, including cephalexin (Keflex®) and cefdinir (Omnicef®).
Nitrofurantoin (Macrobid®, Macrodantin®) also has significant concerns in renal impairment. According to the manufacturer’s prescribing information, it is contraindicated in anuria, oliguria, or significant renal impairment (defined as a CrCL less than 60 mL/minute or clinically significant elevated serum creatinine). However, limited data suggest it is safe and effective for short-term use in patients with a CrCL of 30 to 60 mL/minute, although there appears to be an increased risk of pulmonary adverse events when eGFR is less than 50 mL/minute. In any case, nitrofurantoin should be avoided altogether in patients with a CrCL less than 30 mL/minute, due to the risk of pulmonary toxicity, hepatotoxicity, and peripheral neuropathy.

Renal impairment can affect drug disposition in several ways, often increasing the risk of adverse and toxic effects. Whenever you have a patient with renal impairment, evaluate whether they are taking medications that may be cause for concern and require dose adjustment, and remember that hospice clinicians, pharmacists, and drug information resources can help by providing specific renal dosing recommendations.

By Joelle K. Potts RPh, PharmD, BCGP

REFERENCES:

Aging and Kidney Disease. National Kidney Foundation. Available at: https://www.kidney.org/news/monthly/wkd_aging [accessed 8/8/2022]
Aronoff GR, Bennett WM, Berns JS, Brier ME, Kasbekar N, Mueller BA, et al. Drug Prescribing in Renal Failure: Dosing Guidelines for Adults and Children. 5th American College of Physicians, Philadelphia, PA; 2007.
Renal Impairment. Chapter in: Palliative Care Formulary, 7th Edition (PCF7). Wilcock A, Howard P, Charlesworth S, Eds. Pharmaceutical Press, London, UK. Chapter 17, added April 2017; 715-35.
Drug monographs. Lexcomp Online, Lexi-Drugs Online. Waltham, MA: UpToDate, Inc. https://online.lexi.com.
O’Connor NR, Corcoran AM. End-stage renal disease: symptom management and advance care planning. Am Fam Physician. 2012; 85(7): 705-10.
Kidney Disease: Improving Global Outcomes (KDIGO). KDIGO 2012 clinical practice guideline for the evaluation and management of chronic kidney disease. Kidney International Supplements. Jan 2013; 3(1). Available at: www.kidney-international.org
Macrobid® Prescribing Information. Proctor and Gamble Pharmaceuticals, Inc. Cincinnati, OH. Revised Jan 2009. Available at: https://www.accessdata.fda.gov/drugsatfda_docs/label/2009/020064s019lbl.pdf [accessed 6/13/2022]
Macrodantin® Prescribing Information. Almatica Pharma Inc. Pine Brook, NJ. Revised Mar 2013. Available at: https://www.accessdata.fda.gov/drugsatfda_docs/label/2013/016620s072lbl.pdf [accessed 6/13/2022]
2019 American Geriatrics Society Beers Criteria® Update Expert Panel. American Geriatrics Society 2019 updated Beers Criteria® for potentially inappropriate medication use in older adults. JAGS. 2019; 00: 1-21

Buprenorphine for Pain Management: Pros vs. Cons in the Hospice Population

Wed, 24 Aug 2022 17:37:40 GMT

Buprenorphine is a unique opioid analgesic. It has several benefits (“pros”) for pain management, but it also has a few significant risks (“cons”) that prevent it from being used more frequently in hospice.

For pain management, buprenorphine is available as a buccal film (Belbuca®), a weekly transdermal patch (Butrans®), and an injection solution (Buprenex®). The forms that are most often seen in hospice patients are the buccal film and transdermal patch, which are used routinely as long-acting opioids for chronic pain, and these are the dosage forms we’ll be discussing here. Buprenorphine injection is indicated for acute pain and is not recommended for long-term use, and it is rarely used in hospice. Other dosage forms (monthly subcutaneous injection, 6-month subcutaneous implant, and daily sublingual tablet) are indicated for opioid use disorder and are not FDA-approved for pain management.

What makes buprenorphine unique is the way it binds to various opioid receptors. The most commonly used opioid analgesics (e.g. morphine, oxycodone, fentanyl, and hydrocodone) are full mu-opioid receptor agonists, meaning they bind to and activate the mu-opioid receptor. In contrast, an antagonist blocks a receptor by binding to it without activating it; naloxone (Narcan®) is an excellent example of a mu-opioid receptor antagonist. Buprenorphine is a partial mu-opioid receptor agonist, which means that it binds to the mu-opioid receptor but activates it to a lesser degree than a full agonist. In addition to its effects at the mu-opioid receptor, buprenorphine has activity at three other opioid receptors: it is an antagonist at the delta- and kappa-opioid receptors, and a full agonist at the ORL-1 (opioid receptor-like 1; a.k.a. nociceptin) opioid receptor.

The Pros of Buprenorphine:

Effective for pain. Buprenorphine’s partial agonism at the mu-opioid receptor refers only to its activity level at the receptor, and not to its effectiveness as an analgesic. In fact, buprenorphine’s analgesic effects are comparable to full mu-opioid receptor agonists in a variety of different pain types, including moderate to severe post-operative and cancer pain, osteoarthritis, and chronic low back pain. Buprenorphine is also effective for neuropathic pain.

Lower risk of certain opioid adverse effects. Because of buprenorphine’s unique activity at four opioid receptors, it is less likely to cause several common opioid adverse effects. When compared with most full mu-opioid receptor agonists, buprenorphine has a lower incidence of respiratory depression – although, as with all opioids, this adverse effect is still possible. Because buprenorphine is also less likely to produce euphoria, it has less potential for physical dependence and addiction; as such, it is classified as a Schedule III (C-III) controlled substance. In addition, when compared with the extended-release forms of oxycodone, hydromorphone, and oxymorphone, buprenorphine buccal film causes significantly less nausea, vomiting, constipation, dizziness, and somnolence.

When buprenorphine is compared to morphine, the differences in adverse effect frequency are less pronounced, perhaps due to the dosage forms evaluated (or not evaluated). When comparing buprenorphine buccal film to morphine (dosage form not specified), buprenorphine appears to have just slightly lower incidences of constipation, somnolence, anxiety, and dry mouth. In a 2018 systematic review and meta-analysis of buprenorphine vs. morphine in acute pain management, the only significant difference in adverse effects identified was that buprenorphine was associated with less pruritis. The dosage forms considered in this review varied but were typically morphine injection vs. buprenorphine injection or sublingual tablet (not the patch or buccal film forms of buprenorphine that we usually see in our hospice patients).

Safe in special populations. In addition, buprenorphine is considered safe in populations that we see often in hospice: those with renal impairment, including dialysis; those with mild to moderate hepatic impairment; and the elderly.

The Cons of Buprenorphine:

High cost. Unfortunately, buprenorphine patch and buccal film are relatively high-cost medications, which makes them much less attractive for use in hospice. Depending on the strength, the average cost for the generic weekly patch ranges from approximately $10 to $28 per day; the average cost for the brand buccal film, which is dosed once or twice a day, ranges from approximately $8 to $19 per film.

Dosing limitations and cautions in severe hepatic impairment. A potential concern, especially in hospice patients, is that buprenorphine patch and buccal film both have maximum recommended doses. Also, the dose of the patch should be titrated no more frequently than every 72 hours, while the dose of the buccal film should be titrated no more frequently than every 4 days. Because buprenorphine has primarily hepatic metabolism, there are cautions regarding its use in severe liver impairment; in these patients, the dose of the buccal film should be reduced, and the transdermal patch form is not recommended.

The Verdict:

There are a number of reasons why buprenorphine patch and buccal film are excellent long-acting analgesics for many patients, especially those who are not approaching end of life. However, the cons can be significant, and buprenorphine is usually not preferred as a first- or second-line option for the majority of our hospice patients because other long-acting analgesics are effective and available at a much lower cost (e.g. methadone, morphine extended-release, and many strengths of fentanyl patch). In addition, the fact that buprenorphine patch and buccal film have maximum recommended doses may become an issue at end of life in patients whose pain is rapidly escalating. Of course, the pros and cons must always be weighed for each patient and their specific situation; no doubt there will be some hospice patients for whom buprenorphine patch or buccal film is an ideal choice.

Written by Joelle Potts, PharmD, CGP

REFERENCES:

Lexicomp Online, Lexi-Drugs Online. Waltham, MA: UpToDate, Inc.; July 23, 2022. https://online.lexi.com. [last accessed 7/23/2022]
Buprenorphine Practitioner Resources and Information. Substance Abuse and Mental Health Services Administration (SAMSHA), U.S. Department of Health and Human Services. Programs: Medication-Assisted Treatment (MAT). Last updated 6/24/2021. Available at: https://www.samhsa.gov/medication-assisted-treatment/practitioner-resources [last accessed: 2/5/2022]
Become a Buprenorphine Waivered Practitioner. Substance Abuse and Mental Health Services Administration (SAMSHA), U.S. Department of Health and Human Services. Programs: Medication-Assisted Treatment (MAT). Last updated 6/24/2021. Available at: https://www.samhsa.gov/medication-assisted-treatment/become-buprenorphine-waivered-practitioner [last accessed: 2/5/2022]
Practice Guidelines for the Administration of Buprenorphine for Treating Opioid Use Disorder. U.S. Department of Health and Human Services, Federal Register document number 2021-08961, pages 22439-40; 4/28/2021. Available at: https://www.federalregister.gov/documents/2021/04/28/2021-08961/practice-guidelines-for-the-administration-of-buprenorphine-for-treating-opioid-use-disorder [last accessed 2/5/2022]
Pharmacist’s Manual: An Informational Outline of the Controlled Substances Act. EO-DEA154; revised 2020. Drug Enforcement Administration (DEA), Diversion Control Division. Available at: https://www.deadiversion.usdoj.gov/pubs/manuals/ [last accessed 2/28/2022]
Pharmacological Treatment. Under: Opioids > Medication Assisted Recovery. Indian Health Service (IHS), Rockville, MD. https://www.ihs.gov/opioids/recovery/pharmatreatment/ [accessed 12/9/2021]
Hale M, Garofoli M, Raffa RB. Benefit-risk analysis of buprenorphine for pain management. Journal of Pain Research, 2021:14; 1359-69.
Gudin J, Fudin J. A narrative pharmacological review of buprenorphine: a unique opioid for the treatment of chronic pain. Pain Ther. Published online: 28 Jan 2020.
Childers JW, Lou K, Arnold R. Fast Facts and Concepts #268. Low-dose buprenorphine patch for pain. October 2020. Available at: https://www.mypcnow.org
Davis MP. Twelve reasons for considering buprenorphine as a frontline analgesic in the management of pain. The Journal of Supportive Oncology. Nov-Dec 2012; 10(6): 209-19.
Khanna IK, Pillarisetti S. Buprenorphine – an attractive opioid with underutilized potential in treatment of chronic pain. Journal of Pain Research, 2015:8. 859-70.
White LD, et al. Efficacy and adverse effects of buprenorphine in acute pain management: systematic review and meta-analysis of randomized controlled trials. British Journal of Anaesthesia. 2018; 120(4): 668-78.
Morphine (systemic). Lexicomp Online, Lexi-Drugs Online. Waltham, MA: UpToDate, Inc.; July 20, 2022. https://online.lexi.com. [last accessed 7/23/2022]
Butrans® (buprenorphine patch) prescribing information. Purdue Pharma LP, Stamford, CT. Revised March 2021. Available at: https://butrans.com [last accessed 3/15/2022]
Belbuca® (buprenorphine buccal film) prescribing information. BioDelivery Sciences International, Inc., Raleigh, NC. Revised March 2021. Available at: https://www.belbuca.com. [last accessed 3/15/2022]

Palliative Wound Care

Thu, 26 May 2022 02:01:20 GMT

There are many types of chronic, non-healing wounds. These include pressure ulcers, diabetic ulcers, arterial insufficiency ulcers, venous ulcers, and malignant wounds.

Pressure ulcers are the most common type of wound we encounter as patients decline, become bed bound, and approach end-of-life. Stage 1 and 2 pressure ulcers cause superficial skin changes, and Stage 3 and 4 pressure ulcers affect the deep tissue framework.¹ Pressure ulcers should be staged depending on damage and presence of certain characteristics. It is important to note that if a wound is healing, reverse staging is not done. If a patient has a stage 3 ulcer that is getting better, we would say that the patient has a “healing” stage 3 pressure ulcer.²

A patient’s initial assessment should include a review of their skin and existing wounds, if any, and an assessment of the risk factors that are affecting wound healing. The Braden Scale for Predicting Pressure Sore Risk is one tool used when assessing patients. It is based on sensory perception, moisture, activity, mobility, nutrition, and friction/shear. Keep in mind, most tools used to predict risk do not account for end-of-life decline, so hospice/palliative care patients may be at greater risk than the scales show.³ Other risk factors for chronic non-healing wounds include obesity, tobacco use, vascular issues, diabetes, elderly, radiation therapy, poor self-care, alcohol use, and neurological issues. After the initial assessment, a plan should be developed that aligns with the patient and family’s goals. If there are emotional or spiritual issues that are contributing to poor self-care or alcohol/substance abuse, consider calling on other members of your multi-disciplinary team (i.e., social worker or clergy) for assistance. Therapy goals, which aim to improve quality of life, should be based on patient prognosis, patient factors, heal-ability of existing wound, type of wound, and patient and family wishes. Goals should include preventing new wounds or worsening of existing wounds, prevent/relieve distressing symptoms, reduce discomfort, reduce risk of infection, bleeding, and odor.³

The TIME mnemonic can help us improve wound care.

If a wound has non-viable, deficient tissue, it may need to be debrided. However, stable eschar should be painted with Betadine® and never be debrided.¹² There are many types of debridement techniques including mechanical, autolytic, enzymatic, sharps, surgical, and biologic.¹⁰ Many types of debridement are not appropriate and do not align with goals of care in hospice patients. There are some non-healable wounds that should NOT be debrided. These include arterial wounds in people with Peripheral Artery Disease (PAD) (stable dry gangrene, dry ischemic wound), wounds at risk for bleeding, malignant or inflammatory wounds, lower limb pressure ulcers if arterial insufficiency is present, and wound on patients who are acutely palliative.¹⁰ Most hospice patients have non-healable wounds that should only be debrided if necessary to manage bacterial burden, exudates, and odor.¹⁰

To promote health of the wound, moisture balance must be maintained. The correct dressing will help with this. Dressing choice is based on drainage, non-stick vs absorbent, as well as other factors. Dead space, undermining, and tunneling must be loosely packed or filled with an appropriate dressing. The table below shows the different dressing categories, examples, descriptions, and uses.

Re-evaluate the wound care plan within 2 weeks or if issues arise, or if there are changes in the patient’s condition or patient/family goals. Looking at the edge of the wounds aids in evaluation. Healthy wound edges are attached open and migrating/contracting. Non-healing edges don’t advance or are undermined. Improperly dressed wounds may get tunneling, undermining, and rolled edges. Keep in mind that some patients and family may have difficulty with compliance or procedures and need additional education and support.

Possible wound complications include pain, bleeding, odor, and infection. Moistening dressings before removal, using non-stick dressings, and doing less frequent dressing changes can all help with pain. Using lidocaine 2% gel topically during wound care and/or pretreating with oral morphine or another oral narcotic 30-60 minutes prior to wound care can also help. For pain after dressing changes, consider applying a small amount of viscous lidocaine to the dressing side that contacts the wound.

Malignant wounds are associated with a greater risk of bleeding than other types of wounds. If bleeding is anticipated, it should be discussed with the patient and family, and a plan should be in place. Dark basins, towels and bed linens (not red) can be used to minimize the impact of bleeding. Bleeding can be traumatic for the patient and family. Consider calling on other team members to help provide emotional support if needed. When a wound is at risk for bleeding, use gentle irrigation to cleanse the wound⁴ and stop anticoagulants including aspirin³. Avoid unnecessary dressing changes and debridement. Soak dressings with warm normal saline prior to removal if they adhere to the wound¹³ and use non-stick dressings⁴. If bleeding occurs, calcium alginate dressings can be placed on the wound and direct pressure should be applied for 10-15 minutes. If appropriate, the position can be changed or ice packs can be placed over the wound. Silver nitrate sticks can be used for small localized areas of bleeding. Minimize dressing changes (only changing the dressing if it is saturated with blood). If these methods don’t work, sometimes a sucralfate paste is used to help stop the bleeding.¹³

If wound odor is present, cleanse the wound, treat the cause if possible, and control infection.⁹ Crushed metronidazole (Flagyl®) tablets sprinkled over the wound with dressing changes is an off-label use, but can be effective at controlling odor at a reduced cost. If the wound is in an area where it is hard to sprinkle the crushed metronidazole, it can be mixed with a water-based lubricant and then applied to the wound. For deep tissue infection and odor, oral metronidazole can be used. Honey (Medihoney®) may also be effective for odor, wound pain, and debriding. If these options are ineffective, cadexomer iodine gel or an impregnated dressing (pad) is helpful for odor, beneficial for exudate, and also debrides.⁹ Aromatics can be used in the room to hide the odor. Adsorbents like charcoal (briquettes) or cat litter can be placed discreetly in the room. Baking soda may also be applied between dressing layers. Odor may cause embarrassment, shame, and result in patient isolation.⁹ Multidisciplinary team members can assist in supporting the patient emotionally and spiritually. Taking steps to control odor and talking about it with the patient/family and visitors before they arrive, can be helpful. Chewing spearmint gum, placing peppermint oil under the nose or using Vicks vapor rub can be helpful for the patient and visitors to hide the odor.

Wounds should be continuously assessed for local and systemic infection.¹² Wound swabs cannot diagnose an infection.² All wounds have contamination and many are colonized with bacteria. That does not mean there’s an active infection.¹² Wound cultures are not appropriate for most hospice patients. They can be very painful and are difficult to perform correctly and without contamination. The pus and necrotic tissue in a wound do not indicate the bacteria contained within the tissue. Also, once a culture is obtained, if not delivered to the lab within an hour, must be refrigerated.⁸

The NERDS and STONEES mnemonic is a useful tool to assess for superficial and deep infection.

Localized infections can be cleansed with topical antiseptics. Consider chlorhexidine, which has low toxicity, povidone-iodine (Betadine®) if broad spectrum is needed, and acetic acid (vinegar diluted 1:5 to 1:10) for suspected pseudomonas. Some topical antiseptics can interfere with wound healing. If the wound is healable, try to limit use and discontinue once infection has been controlled.⁸ After cleansing, topical antimicrobial agents can be used. Crushed metronidazole⁹ and cadexomer iodine that were used for odor, can also be used for localized infection. If these are not effective, silver dressing can be used for a short time, but it is a more expensive option and can cause tissue toxicity and resistance with longer use.⁸

Deep tissue infection may cause further systemic infections. Oral antibiotics can be used to treat systemic infections. The choice to use oral antibiotics depends on if the wound is healable, maintenance or non-healable, and the goals of care. If used, the goal is not to heal the wound, but to control the systemic infection. Expected bacteria in our hospice patients’ wounds are gram positive and negative bacteria including anaerobes. Dual oral therapy is used in order to address all of the different types of bacteria anticipated. The antibiotics used in order of preference are:

Amoxicillin/Clavulanate (Augmentin®), plus Trimethoprim/Sulfamethoxazole (TMP/SMX) (Bactrim®)
Clindamycin plus Ciprofloxacin
Doxycycline plus Metronidazole
TMP/SMX (Bactrim®) plus Metronidazole

In summary, it is important to do a thorough assessment of all patients for risk of developing chronic wounds and worsening of existing wounds. The main goal for wound care is to improve quality of life. Using the mnemonics TIME and NERDS & STONEES can help improve wound care. Oral antibiotics should only be considered for wounds with deep tissue or systemic infection, and in cases where treatment is preferred by the patient and family. Members of the multidisciplinary team can help support the patient and family and help increase the quality of life for patients with chronic wounds.

Written by: Karen Bruestle-Wallace, PharmD, BCGP, RPh

References:

Ayello, E. A. (2014, May 12). Pressure ulcer staging. Pressure Ulcer Staging Quality Initiatives. Retrieved January 14, 2022, from https://www.cms.gov/Medicare/Quality-Initiatives-Patient-Assessment-Instruments/IRF-Quality-Reporting/Downloads/IRF-QRP-Training-%E2%80%93-PrU-Staging-May-12-2014-.pdf
Daley, B. J. (2021, April 3). Wound care. Wound Care. Retrieved January 18, 2022, from https://emedicine.medscape.com/article/194018-overview#a5
Emmons, K. R., Dale, B., & Crouch, C. (2014). Palliative wound care, Part 2: Application of Principles. Home Healthcare Nurse, 32(4), 210–222. https://doi.org/10.1097/nhh.0000000000000051
Ferris, F., & von Gunten, C. F. (2015, May). #46 Malignant wounds. Palliative Care Network of Wisconsin. Retrieved January 19, 2022, from https://www.mypcnow.org/fast-fact/malignant-wounds/
Ferris, F., & von Guten, C. F. (2015, May). Pressure ulcer management: Staging and prevention. Palliative Care Network of Wisconsin. Retrieved January 14, 2022, from https://www.mypcnow.org/fast-fact/pressure-ulcer-management-staging-and-prevention/
Kulikov, P. (2018, December 25). Improving Wound Care Using the TIME Framework. The University of San Francisco USF Scholarship: a digital repository @ Gleeson Library | Geschke Center. Retrieved January 19, 2022, from https://repository.usfca.edu/cgi/viewcontent.cgi?article=1177&context=dnp
Nurses Association of Ontario, R. (2019). Project ECHO Skin and Wound Infection Enabler.pdf. Infection Control. Retrieved January 22, 2022, from https://drive.google.com/file/d/1HdkywiJhQjZt4ObrPf60_rnfKLaScCqu/view
Nurses Association of Ontario, R. (Ed.). (2016, May). Assessment and Management of Pressure Injuries for the Interprofessional Team. Clinical Best Practices Guidelines. Retrieved January 20, 2022, from https://wound.echoontario.ca/wp-content/uploads/2019/05/RNAO-2016-Pressure-Injury-BPG.pdf
Patel, B., & Cox-Hayley, D. (2015, August). #218 Managing Wound Odor. Palliative Care Network of Wisconsin. Retrieved January 19, 2022, from https://www.mypcnow.org/fast-fact/managing-wound-odor/
Regional Wound Care Program, S. (Ed.). (2015, April 6). Guideline and Procedures: Wound debridement. SWR Wound Care Program. Retrieved January 19, 2022, from https://swrwoundcareprogram.ca/Uploads/ContentDocuments/WoundDebridement.pdf
Tippett, A. (2018, April 12). The Use of Lidocaine in Managing Wounds. WoundSource Blog. Retrieved January 21, 2022, from https://www.woundsource.com/blog/use-lidocaine-in-managing-wounds
Vera, M. (2020, May 6). Wound Bed Preparation and Beyond. WoundSource. Retrieved January 18, 2022, from https://www.woundsource.com/blog/wound-bed-preparation-and-beyond
Winnipeg Regional, H. A. (Ed.). (2021, April). Malignant fungating wounds - WRHA professionals . Malignant Fungating Wounds, Clinical Practice Guidelines. Retrieved January 18, 2022, from https://professionals.wrha.mb.ca/old/extranet/eipt/files/EIPT-013-007.pdf

The Use of Medical Marijuana in Hospice and Palliative Care

Thu, 26 May 2022 01:40:29 GMT

Cannabis (marijuana) has recently garnered significant national attention as more states vote to legalize both medicinal and recreational forms of the substance. Cannabis use in end-of-life care is increasingly being sought by patients, and organizations are caught between strict federal regulations and waning state laws. Many states have legalized marijuana’s medical use and some have recognized its recreational use as well. However, federally, it is still a Schedule I substance.

Cannabinoids and the Endocannabinoid System

Cannabis exerts its effects on the body by interacting with the endocannabinoid system, which consists of cannabinoid (CB) receptors. There are two main CB receptors in the body, the CB1 and the CB2. CB1 receptors can mainly be found in the brain and spinal cord, whereas the CB2 receptors are mostly located in the periphery. More than a hundred cannabinoids have been identified in the marijuana plant. Of these, tetrahydrocannabinol (THC) and cannabidiol (CBD) have been studied most extensively. THC is thought to interact mostly with the CB1 receptor, whereas CBD seems to have an effect on both the CB1 and CB2 receptors. Furthermore, cannabis can be divided into two primary species: indica and sativa. Indica strains are more CBD dominant, so it binds to CB1 and CB2 receptors, causing increased mental and muscle relaxation. The sativa strain is more THC dominant and is more commonly used for recreational purposes.

Medical Uses of Cannabis

When a state approves the use of cannabis for medicinal purposes, the patient must meet certain criteria in order to be able to use medical marijuana. One of these criteria is a qualifying condition. There are many qualifying conditions for which several states have approved the use of medical marijuana, but evidence that marijuana is actually effective for these conditions is limited. It’s thought that cannabis may play a role in symptom management in neurodegenerative diseases, including Parkinson’s and Huntington’s disease. Studies have found that cannabis helps improve patient-reported symptoms of spasticity and pain associated with multiple sclerosis.

Additionally, cannabis appears to have a role in treating chemotherapy-induced nausea/ vomiting. Marinol® (dronabinol) is a synthetic THC derivative that is FDA approved for the treatment of chemotherapy–induced nausea/vomiting. It also has indications to treat anorexia in AIDS patients. However, since it is a THC derivative, its most frequently reported adverse effect is euphoria.

It is also thought that cannabis may be effective for pain management. Interestingly, there is some evidence that shows cannabis may be effective for refractory neuropathic pain in cancer and in patients with multiple sclerosis. However, some recent studies have shown that the use of cannabis for cancer pain was no better than placebo, and not effective for this type of pain.

Cannabis also appears to have a role in seizure management. In 2018, Epidiolex®, the first US-approved drug made solely from plant-grown cannabis, was approved for specific, rare types of epilepsy.

Routes of Administration

Laws and Regulations Concerning Cannabis Use

Although many states have started to legalize marijuana for medical use, it is still classified as a Schedule I substance at the federal level. As a hospice organization, it is illegal to furnish patients with cannabis. If your patient is taking marijuana for medical purposes, it should be documented and the patient should be offered evidence-based information regarding medical marijuana, but it cannot be provided by the hospice. In those states where medical marijuana is legal, only physicians that are specially certified by the state are able to recommend this substance for their patients who meet certain criteria. Also, marijuana is a cash-only market, which makes payment difficult, and government reimbursement should not be used to reimburse the patient or family.

Within facilities, laws regarding medical marijuana use, storage and administration can depend on state laws and also individual facility policies – it may even depend on what type of facility it is. Many nursing homes, for example, are regulated and funded by the federal government, and are concerned that non-compliance with federal law by allowing cannabis, may result in loss of funding. The past several decades have shown an increase in the use of medical marijuana. As a growing number of states vote to legalize its medicinal use, there is hope that there will be more research done to show its evidence based use and to further define its role in hospice and palliative care.

Written by Kiran Hamid, RPh

References:

Aggarwal SK, “Use of cannabinoids in cancer care: palliative care”, Curr Oncol. 2016 Mar; 23(Suppl 2): S33–S36.

Bereseford L, “How should Hospices Handle Legalized Marijuana” The Lancet, 19 Oct 2016

Häuser W, Fitzcharles M, Radbruch L, Petzke F, “Cannabinoids in Pain Management and Palliative Medicine: An Overview of Systematic Reviews and Prospective Observational Studies, Dtsch Arztebl Int. 2017 Sep; 114(38): 627–634.

https://inhalemd.com/blog/medical-marijuana-allowed-nursing-homes-assisted-living-communities/

Cannabinoids No Help for Cancer Pain, Concludes Meta-Analysis - Medscape - Jan 29, 2020.

Constipation: When Your Patient Can’t “Enjoy the Go”

Wed, 23 Mar 2022 16:05:42 GMT

Overview

Constipation is a common gastrointestinal complaint. It consists of less than three bowel movements per week, and stools that may be hard, dry, lumpy, and difficult or painful to pass. Some patients may feel that not all of the stool has passed after having a bowel movement.¹ Dehydration, bowel motility, and lubrication can also affect bowel movements.⁴

Non-Pharmacological Treatments

Diet and lifestyle changes like increasing fiber, fluids, and activity are not appropriate for many hospice patients. If a patient is on opioids, has minimal fluid intake or poor gut motility, fiber can actually worsen the situation, or even cause an obstruction.⁴

If possible, educate patients to go to the bathroom as soon as they feel the need to defecate. Optimal times are after waking and after meals. The patient’s perception may also need to be altered. As they decline, it may no longer be realistic or appropriate to have bowel movements with the same regularity that they had before.³

Pharmacological Treatments

For patient with hard stools, utilize osmotic agents which include magnesium salts, polyethylene glycol (PEG), sorbitol, and lactulose (reserve for patients with hyperammonemia, sorbitol is better tolerated and more cost effective than lactulose).

The stool softener docusate sodium (Colace®) is not included in the list above. There is no evidence that docusate sodium is effective for constipation. Multiple randomized controlled trials have failed to show any significant efficacy of docusate sodium over placebo. These trials have included hospital, nursing home, hospice, and ambulatory patients.⁵ Continuing docusate sodium, even though the drug itself doesn’t work, has many negative downstream effects, including, but not limited to, creating extra work for the nurse, caregiver, families and patients. Along with increased pill burden and a delay in obtaining effective treatment of constipation, if a patient is having difficulty swallowing medications, they may take docusate sodium over an important comfort medication.⁶ Note, docusate liquid has been known to taste terrible.⁷ If a patient is on the combination product senna/docusate sodium 8.6-100 mg tablet, this can be replaced with plain senna 8.6 mg tablet.⁶ Let’s stop flushing good money down the toilet with habitual use of a laxative (docusate sodium) that doesn’t work.⁷

Stimulant laxatives are used when patients are having motility issues. Oral senna is preferred and the tablets can be crushed. It is also available in liquid and tea form. Bisacodyl is another stimulant laxative available in tablets and suppositories. The suppositories can be used daily or as needed (prn) for constipation.⁴

Lubricant laxatives can be used in patients having painful bowel movements. Mineral oil is a lubricant and available as an enema. It is not recommended to be given orally as pneumonitis can result if it is aspirated. Glycerin suppositories are another lubricant laxative with the added benefit of drawing water into the rectum.⁴

Opioid Induced Constipation (OIC)

Opioid induced constipation (OIC) affects 45-90% of patients on opioids. Patients do not develop tolerance to OIC like most other side effects. Also, there is no evidence that physical activity, scheduled toileting, fiber, or adequate fluid intake are effective. Opioids cause constipation using multiple mechanisms. They affect GI motility, inhibit mucosal transport of electrolytes and fluids, and interfere with the defecation reflex.⁸

Stimulant and osmotic laxatives are effective for opioid-induced constipation (OIC). The preferred oral stimulant is senna. Bisacodyl is also available orally.⁹ Rectal-based laxatives are often used when oral options fail. Warm tap water and milk of molasses enemas can also be used, and can be dosed more frequently (up to every 2 hours).⁸

Refractory Constipation

For refractory constipation, suppositories and enemas can be used. As a last resort, manual evacuation can be done.⁸

If there is a high impaction that has failed to be relieved with other treatments, Vaseline balls can be used. Freeze a dollop of Vaseline, roll/squeeze into pea-sized balls, roll in confectioners’ sugar or cocoa powder for taste. Have the patient swallow 1-2 balls q3-4 hours until BM, may increase if no BM in 12 hours.⁹

Newer Agents for Constipation

There are some newer agents for OIC as well as other types of constipation. However, the first-line agents for constipation are the traditional laxatives. This includes OIC. The traditional laxatives are proven safe and effective, and are also extremely cost effective when compared to the newer agents.

In summary, identify patients who are at risk for constipation and initiate a bowel regimen. All patients on opioids are at risk. Target the cause, when possible. Most elderly patients have complex constipation and OIC has multiple causes, so multiple agents may be needed. Stimulants and osmotics are usually the best options. When needed, utilize suppositories and enemas. Make sure to titrate to maximum doses (senna 8.6 mg tab up to 12 tabs/day, 4 tabs po tid), and if needed, add on other routine (sorbitol) or prn laxatives (mom, suppositories etc.). Newer agents should only be tried after an adequate trial (titrated to maximum doses) of the appropriate traditional laxatives.

Written by Karen Bruestle-Wallace, PharmD, BCGP, RPh

References

Lacy, B. E. (Ed.). (2018, May). Constipation . National Institute of Diabetes and Digestive and Kidney Diseases. Retrieved October 21, 2021, from https://www.niddk.nih.gov/health-information/digestive-diseases/constipation.
3 in PowerPoint. Sonnenberg, A., & Koch, T. R. (1989, January). Epidemiology of constipation in the United States. Diseases of the colon and rectum. Retrieved October 21, 2021, from https://pubmed.ncbi.nlm.nih.gov/2910654/.
4 in PowerPoint De Giorgio, R., Ruggeri, E., Stanghellini, V., Eusebi, L. H., Bazzoli, F., & Chiarioni, G. (2015). Chronic constipation in the elderly: A Primer for the Gastroenterologist. BMC Gastroenterology , 15(1). https://doi.org/10.1186/s12876-015-0366-3
5 in PowerPoint Hallenbeck, J. (2015, May). Fast facts and concepts #15 constipation James Hallenbeck ... FAST FACTS AND CONCEPTS #15 CONSTIPATION. Retrieved October 21, 2021, from https://www.mypcnow.org/wp-content/uploads/2019/01/FF-15-Constipation.-3rd-ed.pdf.
6 in PowerPoint Fakheri, R. J., & Volpicelli, F. M. (2019). Things we do for no reason: Prescribing docusate for constipation in hospitalized adults. Journal of Hospital Medicine , 14(2), 110–113. https://doi.org/10.12788/jhm.3124
7 in PowerPoint Lee, T. C., McDonald, E. G., Bonnici, A., & Tamblyn, R. (2016). Pattern of inpatient laxative use. JAMA Internal Medicine , 176(8), 1216. https://doi.org/10.1001/jamainternmed.2016.2775
McKee, K. Y., & Widera, E. (2016). Habitual prescribing of laxatives—it’s time to flush outdated protocols down the drain. JAMA Internal Medicine , 176(8), 1217. https://doi.org/10.1001/jamainternmed.2016.2780
Badke, A., & Rosielle, D. A. (2015, April). FF and Concepts #294 Opioid Induced Constipation Part 1: Established Management Strategies . FF-294 Opioid Constipation. Retrieved October 21, 2021, from https://www.mypcnow.org/wp-content/uploads/2019/03/FF-294-opioid-constipation-.pdf.
Shah, S.; Madison, M.; Speer, K. ProCare HospiceCare, Hospice Medication Utilization Guidelines (HUGS). Gainesville, GA
Lexicomp Online, Lexi-Drugs, Waltham, MA: UpToDate, Inc.; Oct. 18, 2021. https://online.lexi.com . Accessed Oct 20, 2021.
Crockett, S. D., Greer, K. B., Heidelbaugh, J. J., Falck-Ytter, Y., Hanson, B. J., & Sultan, S. (2019). American Gastroenterological Association Institute guideline on the Medical Management of opioid-induced constipation. Gastroenterology, 156(1), 218–226. https://doi.org/10.1053/j.gastro.2018.07.016

Focus on Anxiety, Agitation, and Terminal Restlessness in the Hospice Patient

Mon, 17 Jan 2022 19:22:23 GMT

Anxiety is one of the most common symptoms for hospice patients. It has been reported within 20% to 50% of patients with advanced cancer. While the impact of anxiety is recognized, anxiety management in palliative care is a major challenge due to a variety of contributing factors. Timely identification, support, and treatment of anxiety are essential in patients with limited life expectancy. Anxiety management benefits from a multi-dimensional team approach. From physicians to nurses to social workers and spiritual care – all disciplines can play a role in helping alleviate anxiety. There are several etiologies behind anxiety in hospice patients – including metabolic causes, drug withdrawal, and adverse drug effects. Anxiety has cognitive, emotional, behavioral, and physical manifestations ranging from mild/occasional to a severe/constant state of anxiousness.

Non-pharmacological management of anxiety may include:

Deep breathing
Spiritual care
Supportive care (previously referred to as palliative care)
Complementary therapy (including mind-body techniques, music therapy, visual imagery, aromatherapy)

Benzodiazepines (including lorazepam or alprazolam) are considered the mainstay of therapy in the management of anxiety. Choice of benzodiazepines depends on the following patient-specific factors:

Duration of action
Desired onset of action
Route of administration available
Dosing schedules

Antidepressants are another frequently used class of medications to treat anxiety. Selective Serotonin Reuptake Inhibitors (SSRIs including escitalopram or sertraline) are a frequently used class. Even though they fall under the pharmacologic category "antidepressants", these medications can have a powerful effect on chronic anxiety. By regulating brain chemistry, these agents help further prevent episodes of anxiety and might help patients rely on benzodiazepines less. Since excessive use of benzodiazepines can cause sedation and affect valuable moments with a loved one nearing end of life, taking a preventative medication may be a better option. The limitation to the use of antidepressants for chronic anxiety at the end of life is that they need time to work, taking up to six weeks for full clinical effect. Some patients reaching the end of their lives might not have this much time and should rely solely on as- needed medications, such as benzodiazepines.

Agitation is a term that describes anxious, restless and unsettled behavior. It can be linked to emotional, physical, or spiritual distress. Terminal agitation refers to agitation that occurs in the last few days of life. Terminal agitation may also be described as terminal restlessness, terminal anguish, confusion at the end of life, or terminal delirium. These terms all have different meanings, but do overlap. Agitation can come on suddenly or gradually and often comes and goes. Signs and symptoms of terminal agitation can include any of the following: confusion, moaning, hallucinations, and sometimes angry and aggressive behavior. There can be many possible causes for agitation, including uncontrolled pain or discomfort, urinary retention, infection, sepsis, or organ failure.

Neuroleptics, also known as antipsychotic medications, are used to treat and manage symptoms of many psychiatric disorders. They fall into two classes: first-generation or "typical" antipsychotics, and second-generation or "atypical" antipsychotics. Haloperidol and Chlorpromazine are two first-generation antipsychotics used to treat agitation.

Second Generation (Atypical) Antipsychotics

Olanzapine (Zyprexa®)

Tablet, ODT (oral disintegrating tab)
2.5-5 mg daily
Max/day: 20mg
May cause hyperglycemia
Anticholinergic effects

Quetiapine (Seroquel®)

Tablet, Tablet, XR
25-50 mg Q8-12h
Max/day: 800mg
Preferred in Parkinson’s disease over other antipsychotics
Anticholinergic effects

Risperidone (Risperdal®)

Tablet, Solution, oral, ODT
1-3 mg BID
Max/day: 16mg
Antipsychotics are appropriate when psychosis is suspected to be the primary cause of agitation/aggression

When an individual is in the final days of life, terminal restlessness is often a common symptom. Definitions of terminal restlessness include the following: the thrashing or agitation that may occur in the last days of life. Frequently, it is associated with impaired consciousness, anxiety, and often, involuntary muscle twitching or jerks. Agitation and terminal restlessness often present together in hospice patients. It is estimated that 42% of all dying patients experience restlessness and agitation in the last 48 hours of life.

The pharmacological involvement of terminal restlessness involves options such as: haloperidol, atypical antipsychotics like olanzapine, risperidone, and quetiapine, or benzodiazepines like lorazepam or midazolam may be appropriate.

For assistance in determining the best course of treatment for your patient’s specific symptoms, please contact a ProCare HospiceCare pharmacist for a symptom management consultation. We would be happy to assist.

Written by Jennifer Procaccino, PharmD

References

Zweers D, de Graeff A, Duijn J, de Graaf E, Witteveen PO, Teunissen SCCM. Patients’ Needs Regarding Anxiety Management in Palliative Cancer Care: A Qualitative Study in a Hospice Setting. American Journal of Hospice and Palliative Medicine®. 2019;36(11):947-954. doi:10.1177/1049909119846844.
Anxiety. Palliative Care Guideline Plus. Available from: https://book.pallcare.info/index.php?tid=47&searchstring=anxiety . Accessed on September 16, 2021.
Stoklosa J, Patterson K, et al. Anxiety in Palliative Care- Causes and Diagnosis. Available from: https://www.mypcnow.org/fast-fact/anxiety-in-palliative-care-causes-and-diagnosis/
National Cancer Institute. Adjustment to Cancer: Anxiety and Distress. Available from: https://www.cancer.gov/about-cancer/coping/feelings/anxiety-distress-hp-pdq . Accessed on September 16, 2021.
Morrow A. Symptoms and Management of End-of-Life Anxiety. Very well health. Available from: https://www.verywellhealth.com/managing-anxiety-1132473 . Accessed on September 16, 2021.
Buckley L. Case-based learning: anxiety disorders. The Pharmaceutical Journal. Available from: https://pharmaceutical-journal.com/article/ld/case-based-learning-anxiety-disorders . Accessed on September 6, 2021.
Terminal agitation at end-of-life. Marie Curie. Available from: https://www.mariecurie.org.uk/professionals/palliative-care-knowledge-zone/symptom-control/agitation . Accessed on September 16, 2021.
Lexicomp Online, Lexi-Drugs Online, Hudson, Ohio: Lexi-Comp, Inc.; 2021; September 16, 2021.
Head B, Faul A. Terminal restlessness as perceived by hospice professionals. Am J Hosp Palliat Care. 2005 Jul-Aug;22(4):277-82. doi: 10.1177/104990910502200408. PMID: 16082913

A Focus on Infectious Diseases: When are Antibiotics Really Necessary?

Mon, 17 Jan 2022 19:14:29 GMT

The use of antibiotics is an ongoing ethical debate in hospice care as it can be perceived to be less aggressive/invasive than other curative/life-prolonging interventions (e.g., intubation, dialysis, chemotherapy, etc.). Hospice patients are especially vulnerable to infections and have high rates of resistant bacteria due to long-term chronic illness. However, there are no guidelines directing appropriate antibiotic decision-making in hospice patients. Therefore, hospice-related infectious disease studies seek to determine if antibiotics provide symptom relief and/or prolong survival in our patient population.

Risks Associated with Antibiotic Treatment:

Adverse outcomes of drug administration (pill burden, drug interactions, side effects, cost)
Secondary infections (Clostridium difficile, Candida)
Multi-drug resistant organisms (MDRO)
Prolonged survival may result in prolonged suffering

Factors That May Influence the Decision Not to Treat:

Dysphagia (patient is unable to swallow)
The patient has a severe infection and aggressive treatment is not a goal of care (intravenous antibiotics are recommended and oral antibiotics may have little effect on overall outcome)
Expected prognosis is less than the recommended duration of the antimicrobial course
Patient/family goal is purely palliative (e.g., morphine, antipyretics)

Areas of Potential Antibiotic Misuse:

Prophylactic antibiotic for urinary tract infection (UTI)
Empiric prescribing without microbiological investigation
Treatment of asymptomatic bacteriuria
Widespread prescribing for upper RTIs or acute bronchitis
Prolonged duration of antibiotic treatment
Widespread prescribing of quinolones as empiric treatment for UTIs
Broad-spectrum or parenteral antibiotic treatment for elderly individuals with advanced dementia or end-stage illness

What Does the Literature Say?

Consider two important studies assessing whether antibiotics prolong survival. Volicer, et al. first determined that survival rate increased for less severe infections, but there was no difference in survival outcome for severe infections. A follow-up study by Givens, et. al. determined that patients treated with antibiotics (PO, IM, & IV) had greater survival rate, but experienced less comfort.

Additionally, a meta-analysis performed by Rosenberg, et. al. identified eight studies measuring symptom response following antimicrobial therapy. The primary findings included that the methods of symptom assessment were highly variable making it difficult to draw conclusions. Also, symptom improvement varies by indication. UTIs (in two studies) appeared to experience the greatest improvement following antimicrobial therapy.

An Important Infection to Remember:

Asymptomatic bacteriuria (ASB) is defined as the presence of 1+ species of bacteria growing in the urine at specified quantitative counts (≥105 colony-forming units [CFU]/mL or ≥108 CFU/L), regardless of the presence of pyuria, in the absence of signs or symptoms attributable to UTI.

Signs/Symptoms of UTI:

P ain: suprapubic pain, flank pain
U rinary-specific: frequency, urgency, hematuria, dysuria
S ystemic: fever, chills, marked fatigue or malaise beyond baseline

If any of the above signs/symptoms present, then perform a urinalysis (UA).

Please note that foul-smelling or cloudy urine, or mental status changes alone does not indicate a UTI.

Furthermore, in older patients with functional and/or cognitive impairment with bacteriuria and delirium (e.g., acute mental status change, confusion) and without local genitourinary symptoms or other systemic signs of infection (e.g., fever or hemodynamic), it is recommended to assess for other causes with careful observation, (e.g. recent fall) rather than immediately initiate antimicrobial treatment.

If you suspect that your patient may have an infection, please reach out to a hospice clinical pharmacist or alternatively, the patient’s physician, to discuss whether treatment would be appropriate, based on the patient and their presenting symptoms.

Written by: Shaun Gutstein, PharmD

References:

Albrecht JS, McGregor JC, Fromme EK, et. al. A nationwide analysis of antibiotic use in hospice care in the final week of life. J Pain Symptom Manage. 2013; 46(4):483-490.
Enck RE. Antibiotic use in end-of-life care: a soft line? Am J Hosp Palliat Care. 2010; 27(4):237-8.
Hersh AL, King LM, Shapiro DJ, et. al. Unnecessary Antibiotic Prescribing in US Ambulatory Care Settings, 2010-2015. Clin Infect Dis. 2021; 72(1):133-137.
Hersh AL, King LM, Shapiro DJ, et. al. Unnecessary Antibiotic Prescribing in US Ambulatory Care Settings, 2010-2015. Clin Infect Dis. 2021; 72(1):133-137.
Morrison RS, Ahronheim JC, Morrison GR, et. al. Pain and discomfort associated with common hospital procedures and experiences. J Pain Symptom Manage. 1998 Feb;15(2):91-101.
Lim CJ, Kong DC, Stuart RL. Reducing inappropriate antibiotic prescribing in the residential care setting: current perspectives. Clin Interv Aging. 2014; 9:165-177.
Volicer L, Rheaume Y, Brown J, et al. Hospice approach to the treatment of patients with advanced dementia of the Alzheimer type. JAMA. 1986;256(16):2210-2213.
Givens JL, Jones RN, Shaffer ML, et. al. Survival and comfort after treatment of pneumonia in advanced dementia. Arch Intern Med. 2010; 170(13):1102-7.
Fabiszewski KJ, Volicer B, Volicer L. Effect of antibiotic treatment on outcome of fevers in institutionalized Alzheimer patients. JAMA. 1990;263(23):3168-3172.
Rosenberg JH, Albrecht JS, Fromme EK, et al. Antimicrobial use for symptom management in patients receiving hospice and palliative care: a systematic review. J Palliat Med. 2013;16(12):1568-1574.
Juthani-Mehta M, Malani PN, Mitchell SL. Antimicrobials at the end of life: An opportunity to improve palliative care and infection management. JAMA. 2015; 314 (19): 2017-8.
Datta R, Topal J, McManus D, et al. Perspectives on antimicrobial use at the end of life among antibiotic stewardship programs: A survey of the Society for Healthcare Epidemiology of America Research Network. Infect Control Hosp Epidemiol. 2019;40(9):1074-1076.
Nicolle LE, Gupta K, Bradley SF, et. al. Clinical Practice Guideline for the Management of Asymptomatic Bacteriuria: 2019 Update by the Infectious Diseases Society of America. Clin Infect Dis. 2019; 68(10):e83-e110.

Discontinuing Dementia Treatment Medications at End of Life

Mon, 11 Oct 2021 18:12:09 GMT

There are currently three categories of dementia treatment medications:

Cholinesterase Inhibitors: donepezil (Aricept®), rivastigmine (Exelon®), galantamine (Razadyne®) – These medications increase levels of acetylcholine, a neurotransmitter in the brain, by preventing the enzyme acetylcholinesterase from breaking it down.

N-Methyl-D-Aspartate (NMDA) Receptor Antagonist: memantine (Namenda®) – Memantine blocks the NMDA type of glutamate receptor during periods of overstimulation.

Anti-Amyloid Monoclonal Antibody: aducanumab (Aduhelm®) – Aducanumab reduces the amyloid beta plaque deposits that occur in Alzheimer’s disease. The FDA granted accelerated approval for this medication on June 7, 2021, with continued approval contingent upon whether post-approval trials verify its clinical benefit. At this time, it is recommended for initiation only in the mild stage of dementia or cognitive impairment.

Discontinuation of dementia treatment medications should be considered in the following situations:

When they are no longer demonstrating benefit. The primary goals of therapy for the Cholinesterase Inhibitors and memantine are to maintain cognition and preserve function (e.g., the activities of daily living (ADLs)). In some cases, a secondary goal is the management of psychological/behavioral symptoms. Unfortunately, the improvement in functional and/or cognitive status conferred by Cholinesterase Inhibitors is usually small and of relatively minor clinical significance. In addition, they have not been well studied in patients in advanced stages of dementia and usually become less effective as dementia progresses. As a result, they are typically thought to be of questionable benefit in patients with advanced dementia.

When the risks outweigh the benefits – for example, if they are causing adverse effects. Some of the most common adverse effects for Cholinesterase Inhibitors include anorexia/decreased appetite, weight loss, nausea, vomiting, and diarrhea. Memantine is generally well tolerated in most individuals, although confusion, dizziness, and headache can occur.

To decrease tablet burden. The discontinuation of non-essential medications is a goal for all hospice patients, as a higher tablet burden can be associated with a lower quality of life. Decreasing tablet burden becomes an even more urgent concern when patients are having difficulty swallowing or starting to refuse medications, which often occurs as dementia progresses.

How to discontinue Cholinesterase Inhibitors and/or memantine:

If the patient is taking anything higher than the lowest dose, gradually taper the dose before discontinuation. If these medications are abruptly discontinued at higher doses, a withdrawal syndrome can occur (see below for typical symptoms of withdrawal). At end-of-life, it is typically recommended to reduce the dose of these medications by 25-50% every 1-2 weeks, although more gradual taper methods may be utilized when appropriate.

Taper one medication at a time whenever possible so the patient’s response and reaction to the dose reduction can be more clearly assessed. Consider tapering the Cholinesterase Inhibitor first, and then memantine second. Or if time is short (e.g., patient is expected to stop swallowing soon), you could start tapering the medication with the higher relative dose first.

Monitoring and potential outcomes during the taper and after discontinuation:

It is possible that discontinuation of Cholinesterase Inhibitors and/or memantine may worsen cognitive function, and this decline may not be reversible. In addition, some trials have found that discontinuation of Cholinesterase Inhibitors may result in worsening neuropsychiatric and functional status. However, it is important to note that these trials included patients with all stages of Alzheimer’s (mild to severe), and predominantly involved abrupt discontinuation of the medications rather than a gradual taper. Thus, it is unclear if this decline is a common or clinically significant occurrence for patients who have advanced dementia and who have utilized a gradual taper method before discontinuation.

More importantly for our hospice population, discontinuing Cholinesterase Inhibitors has not been found to affect the patient’s global assessment of change or quality of life when compared with those continuing the medication.

Symptoms of withdrawal syndrome that can occur after abrupt discontinuation:

Cholinesterase Inhibitors: Agitation, aggression, hallucinations, reduced consciousness, abrupt cognitive decline.

Memantine: Behavioral disturbances.

If behaviors or negative neuropsychiatric symptoms occur after dose reduction or discontinuation of dementia treatment medications, the timing of the symptoms may help to determine whether they are due to the change in medication vs. patient decline or another cause.

If negative symptoms occur in the first week after a dose reduction or discontinuation, it could indicate that the patient is having an adverse drug withdrawal rection. It would typically be recommended to restart the previous dose, and then consider a more gradual taper in the future, when appropriate.

If negative symptoms occur approximately 2 to 6 weeks after a dose reduction or discontinuation, it could indicate that the medication was providing benefit (unless there is another apparent cause of the symptoms, such as UTI, pain, etc.). Hospice may consider restarting the medication, if appropriate.

If negative symptoms occur between 6 and 12 weeks after a dose reduction or discontinuation, it could indicate either of the above or progression of the patient’s underlying condition. Symptom management in this situation would depend on a number of patient-specific factors (e.g., ability to swallow, prognosis). Consider utilizing non-pharmacologic measures and/or other medications, such as antipsychotics or anti-anxiety medications, if appropriate.

Written by: Joelle Potts, PharmD, RPh, BCGP

References:

1. Lexicomp Online, Lexi-Drugs Online, Hudson, Ohio: UpToDate, Inc.; 2021.

2. Shaw G. FDA narrows Aduhelm label. Pharmacy Practice News, Online First; Jul 12 2021. Available at: https://www.pharmacypracticenews.com/Online-First/Article/07-21/FDA-Narrows-Aduhelm-Label/64066 [accessed 7/22/2021]

3. Peron EP, Slattum PW, Powers KE, Hobgood SE. Alzheimer Disease. Chapter in: Pharmacotherapy: A Pathophysiologic Approach. DiPiro JT, et al editors. 10th Edition, 2017. McGraw Hill Education, New York. 797-813.

4. Epperly T, Dunay MA, Boice JL. Alzheimer disease: Pharmacologic and nonpharmacologic therapies for cognitive and functional symptoms. Am Fam Physician. 2017; 95(11): 771-778.

5. AMDA – The Society for Post-Acute and Long-Term Care Medicine. Recommendation regarding prescribing/continuing acetyl cholinesterase inhibitors or N-Methyl-D-Aspartate antagonists in patients with advanced dementia. Nov 20, 2020; www.choosingwisely.org. Available at: https://www.choosingwisely.org/clinician-lists/14amda-dont-routinely-prescribe-or-continue-acetyl-cholinesterase-inhibitors-or-n-methyl-d-aspartate-antagonists-in-patients-with-advanced-dementia/?highlight=dementia [accessed 5/1/2021]

6. Mitchell SL. Care of patients with advanced dementia. In: UpToDate, Morrison RS and Yaffe K (Section Editors), Wilterdink JL (Deputy Editor). Available at: https://www.uptodate.com/contents/care-of-patients-with-advanced-dementia [accessed 5/5/2021]

7. Liao P, Perri GA. Fast Facts and Concepts #354: Deprescribing cholinesterase inhibitors at the end of life. May 2018. Available at: https://www.mypcnow.org

8. Morrison LJ, Liao S. Fast Facts and Concepts #174: Dementia medications in palliative care. Revised August 2016. Available at: https://www.mypcnow.org

9. Parsons C, et al. Withdrawal or continuation of cholinesterase inhibitors or memantine or both, in people with dementia. Cochrane Database of Systematic Reviews. Feb 3, 2021. [Abstract]

10. Kwak YT, Han I-W, Suk S-H, Koo M-S. Two cases of discontinuation syndrome following cessation of memantine.

Geriatr Gerontol Int. 2009 June; 9(2): 203-5. [Abstract]

11. Steinman M, Reeve E. Deprescribing. In: UpToDate, Schmader KE (Section Editor), Givens J (Deputy Editor). Available at: https://www.uptodate.com/contents/deprescribing?sectionName=Cholinesterase%20inhibitors%20and%20memantine&topicRef=86250&anchor=

H4018874073&source=see_link#H4018874073 [accessed 5/5/2021]

COVID 19 and The Impact on the Hospice Nurse

Mon, 02 Aug 2021 18:08:54 GMT

For healthcare workers, the toll of the COVID-19 pandemic has been indescribable. There have been few health events in modern times that have caught healthcare professionals as unprepared as the novel Coronavirus. There are roughly 28 million nurses working globally, constituting approximately 59% of the health sector and delivering up to 90% of care services. With regard to the hospice population, the strain on nurses is extraordinarily high.

In a survey of 2,109 palliative care specialists, nurses had 1.61 higher odds of reporting burnout compared to physicians, and those who reported burnout had 1.40 times the odds of leaving the field early. Considering these sobering numbers, what are some ways to help combat their overall well-being? The National Academy of Medicine’s recommendations for clinician well-being during the COVID-19 pandemic include the following:

Meeting basic needs (e.g., food, sleep, exercise)
Taking breaks whenever possible
Keeping connected with colleagues to assist in stress, fear, and anxiety management
Respecting differences in how people cope and manage the COVID-19 experience
Staying updated with reliable sources of information and minimizing overexposure to media
Performing ongoing self-reflection and self-assessments of one’s own mental health and emotional needs
Seeking support from peers, managers, and professional help, as needed

Whether we incorporate one or all the measures previously mentioned, it’s of the utmost importance to remember to take care of oneself. Prioritize your health, both physical and mental, to optimize your well-being. Hospice patients benefit from their nurses tremendously, and during these difficult times, it’s crucial that nurses make themselves a priority, as well.

ProCare HospiceCare deeply values its connection and collaboration with our nurses, as well as our physicians. We are honored to deliver meaningful, patient-centered care alongside our partners. We aim to provide streamlined service and remain available 24/7/365 to serve you and your patients.

Written by: Jennifer Procaccino, Pharm.D.

References

1. Paice JA, Wholihan D, Dahlin C, et al. Palliative Nursing: The Core of COVID-19 Care. J Hosp Palliat Nurs. 2021;23(1):6-8.

2. Rosa WE, Gray TF, Chow K, et al. Recommendations to Leverage the Palliative Nursing Role During COVID-19 and Future Public Health Crises. J Hosp Palliat Nurs. 2020;22(4):260-269.

Pruritus in the Hospice Patient: Causes and Management

Fri, 09 Jul 2021 18:07:28 GMT

Pruritus, also known as itching, is not the most common symptom seen in our patients at end of life, but it can be distressing and adversely affect quality of life. Pruritus can be described as an unpleasant sensation of the skin or mucous membranes that provokes the desire to scratch or rub. There are several chemical mediators, known as “pruritogens,” that are involved in the pathophysiology of itching. Although histamine is the best known pruritogen, there are several others, including serotonin, cytokines and opioids, that can play a role. This helps explain why not all itching sensations respond to treatment with antihistamines.

Common disease states/conditions seen in the hospice setting that are usually associated with pruritus include chronic renal failure, cholestasis due to liver disease, malignancy, opioid-induced pruritis, and senility (i.e. senile itch).

General skin care measures are recommended for all patients, regardless of the cause of pruritus. Dry skin can accompany and exacerbate all causes of pruritus; therefore, measures to regularly lubricate the skin with nonfragrant topical emollients, especially after bathing, are important. Patients should be educated on wearing nonirritating and loose clothing, avoiding skin irritants such as perfumes, and maintaining a cool, humidified environment.

To help identify and determine how to manage causes of pruritis in your patient, our clinical pharmacists are available to assist 24/7/365. We look forward to hearing from you!

Written by: Kiran Hamid, R.Ph.

References:

1. Dalal, S. Overview of pruritus in palliative care. In: UpToDate, Givens, J (Ed), UpToDate, Waltham, MA, 2021.

2. Seccareccia D, Gebara N. Pruritus in palliative care: Getting up to scratch. Can Fam Physician. 2011;57(9):1010-e319.

3. Andreas E. Kremer, et al. (2014). Receptors, cells and circuits involved in pruritus of systemic disorders. Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease, Volume 1842 (Issue 7) Pages 869-892. Retrieved from https://doi.org/10.1016/j.bbadis.2014.02.007

4. Berger TG, Steinhoff M. Pruritus and renal failure. Semin Cutan Med Surg. 2011;30(2):99-100. doi:10.1016/j.sder.2011.04.005

5. Tajiri K, Shimizu Y. Recent advances in the management of pruritus in chronic liver diseases. World J Gastroenterol. 2017;23(19):3418-3426. doi:10.3748/wjg.v23.i19.3418

6. Yosipovitch G. Chronic pruritus: a paraneoplastic sign. Dermatol Ther. 2010;23(6):590-596. doi:10.1111/j.1529-8019.2010.01366.x

7. Singh F, Rudikoff D. HIV-associated pruritus: etiology and management. Am J Clin Dermatol. 2003;4(3):177-88. doi: 10.2165/00128071-200304030-00004. PMID: 12627993.

8. Cohen KR, Frank J, Salbu RL, Israel I. Pruritus in the elderly: clinical approaches to the improvement of quality of life. P T. 2012;37(4):227-239

Managing Drug Interactions in the Hospice Patient

Tue, 27 Apr 2021 18:04:06 GMT

“Drug interaction” generally refers to an interaction between two or more drugs that alter the performance of at least one of the interacting drugs. Prescription and over-the-counter (OTC) medications, nutritional supplements, herbal products, foods, diagnostic agents, and other chemical substances have the potential to participate in interactions. These interactions may alter medication absorption, distribution, metabolism, or elimination, which can, in turn, change their concentration, efficacy, or potential to cause adverse effects. Because drug interactions are so common, interactions are generally expressed in “levels of severity” to help identify the degree of risk.

Even though some medications such as benzonatate (Tessalon Perles®) do not participate in any known drug interactions, the majority of medications do have the propensity to “interact” with other medications, as well as foods, beverages, substances, or even medical conditions. Significant interpatient variability exists, in that potential or expected drug interactions do not always result in an actual clinically significant outcome. Genetic variability, including enzymatic polymorphism, is believed to play a key role in creating this variability. The Medicare Hospice Conditions of Participation (CoPs) state that comprehensive assessments must take into consideration a patient’s drug profile, including actual or potential drug interactions. Thus, a case-by-case comprehensive medication review is recommended for each patient to assess the risks vs. benefits of a potential drug interaction.

Metabolic Interactions:

Metabolic drug interactions, which are primarily mediated by the Cytochrome P450 (CYP450) enzymes in the liver, are generally considered to be the most numerous and significant due to their ability to increase or decrease the concentration of certain medications. Upwards of 90% of drugs are metabolized in some way by these enzymes. Management of clinically significant metabolic drug interactions is typically achieved by reducing or increasing doses of an interacting medication depending on how it metabolically interacts. Dose changes might be required empirically (i.e. before the new interacting drug is administered), or it may be acceptable to adjust doses during therapy as needed, while closely monitoring the patient’s response. However, some interactions may not be clinically significant and may require no action outside of monitoring the patient. Other metabolic drug interactions are so significant that they should be avoided altogether.

Absorption Interactions:

Absorption interactions, whereby one or more drugs directly interfere with the absorption of another, are also common. However, absorption interactions may be more easily managed than metabolic interactions by simply separating the timing of doses — check with a pharmacist or refer to a reliable drug information resource for recommended separation times. A common example is the requirement to separate the administration of ciprofloxacin (or any antibiotic in the fluoroquinolone class) from fortified foods/drinks (e.g. yogurt) and/or minerals (e.g. multivitamin or certain antacids that contain calcium, aluminum or magnesium) by several hours.

Synergistic & Antagonistic Interactions:

Other common drug interactions in hospice and palliative care include synergistic (also known as “cumulative”) interactions, as well as antagonistic interactions. Common synergistic drug interactions include the serotonergic agents (where multiple drugs with serotonergic activity may result in serotonin syndrome), QT-prolonging agents (where multiple drugs which prolong the QT interval may result in Torsades de Pointes and/or sudden cardiac death), and anticholinergic agents (where multiple drugs with anticholinergic effects may result in anticholinergic syndrome). Other examples of synergistic groups include constipating agents, ototoxic agents, agents that increase bleeding risk, and CNS depressants. On the other hand, antagonistic interactions (where two or more drugs have opposing effects) are also common. An example of an antagonistic interaction is the combination of an antipsychotic such as haloperidol, which can worsen movement disorders, and carbidopa-levodopa, which is used to improve movement disorders. The risk of this interaction may be minimized by converting the offending antipsychotic to quetiapine (Seroquel®), which has less propensity to interact with movement disorder medications as compared to other antipsychotics. Another antagonistic interaction is the use of midodrine to prevent hypotension and orthostasis while taking a blood pressure medication, which can cause hypotension and orthostasis. Many hospice patients have low blood pressure and/or a relaxed requirement to control blood pressure. Thus, these blood pressure lowering medications might be stopped or tapered off, avoiding the need for midodrine.

In hospice care, certain drug interactions may be unavoidable or difficult to manage due to complex drug regimens and the desire to treat distressing symptoms. Polypharmacy can make it nearly impossible to predict the overall outcome of numerous interacting medications; thus deprescribing unnecessary and non-essential medications becomes a key management strategy for avoiding drug interactions. A case-by-case comprehensive medication review is recommended for each patient to assess the risks vs. benefits of a potential drug interaction and how to best manage it. To help identify and determine how to manage any clinically significant drug interactions, or for deprescribing recommendations, our clinical pharmacists are available to assist 24/7/365. We look forward to hearing from you!

Written by: Brett Gillis, Pharm.D., R.Ph

References:

1. Ansari J. Drug interaction and pharmacist. J Youn Pharm 2010;2(3):326-31.

2. Carpenter M, et al. Clinically relevant drug-drug interactions in primary care. Am Fam Physician 2019;99(9):558-64.

3. Medicare and Medicaid programs: hospice conditions of participation. 2008;73 FR 32087:32087-220.

4. State operations manual: appendix m 2020;200.

5. Falconi G, et al. Drug interactions in palliative care. NCBI 2020.

6. Farzam K, et al. QT prolonging drugs. NCBI 2020.

7. Horn, et al. How to address a drug interaction alert. Pharm Tim 2010.

8. Lexicomp: Wolters Kluwer Health, Inc. https://online.lexi.com (accessed 2021).

9. Spanakis M, et al. Empowering patients to avoid clinical significant drug-herb interactions. Med 2019;6(26).

10. The Royal Children’s Hospital Melbourne. Anticholinergic syndrome. SCV

11. Volpi-Abadie J, et al. Serotonin syndrome. Ochs J 2013;13:533-40

A Review of Managing Less Common End-of-Life Symptoms

Mon, 22 Feb 2021 19:01:22 GMT

In the hospice setting, many healthcare practitioners are familiar with more common end-of-life symptoms. These include pain, constipation, nausea and/or vomiting, anxiety, agitation, or dyspnea. However, there are some less common symptoms that hospice patients may encounter, which may include hiccups, metallic (or bad) taste, and dizziness.

The definition of a hiccup is an involuntary spastic contraction of the diaphragm and intercostal muscles that leads to inspiration of air, followed by the abrupt closure of the vocal folds (Jeon et.al., 2018). Hiccups can be classified based on duration – hiccup bouts can last up to 48 hours, persistent hiccups anywhere from 48 hours to 1 month, and intractable hiccups that tend to last more than a month. Hiccups can be commonly experienced in any individual (adults, children, infants, and in utero).

The prevalence of hiccups is not well known. No racial, geographical, or socioeconomic variations have been noted. In general, the prevalence of hiccups is thought to be higher in children, men, and patients with comorbid conditions. Most hiccups are benign and self-limited, ceasing within hours. Data indicates that persistent and intractable hiccups can be extremely distressing and have a significant negative impact on quality of life for almost 1 in 10 palliative care patients.

Another symptom hospice patients may experience is a type of taste disorder characterized by a persistent metallic, bitter, or salty taste in the mouth. This is called dysgeusia, which is a distortion of the sense of taste. It often occurs in older people, usually because of medications or oral health problems. It is the most common taste disorder.

Treatment options for dysgeusia include: the removal of the offending medication, if appropriate; use of sugar-free gum or hard candies (mint, lemon, or orange flavors suggested); rinsing mouth with a salt and baking soda solution before meals; or adding sweeteners like maple syrup or agave nectar to tame the taste issues.

Finally, dizziness is a term used to describe a range of sensations such as feeling faint, woozy, weak, or unsteady. Dizziness that creates the false sense that you or your surroundings are spinning or moving, is called vertigo. The feeling of spinning often starts suddenly, usually initiated by moving the head, and lasts anywhere from a few seconds to minutes. Risk factors include age and/or previous episodes of dizziness. Older adults are more likely to have medical conditions that cause dizziness, especially a sense of imbalance, and are more likely to use medications that can cause dizziness.

People experiencing dizziness may describe any of number of sensations, including a false sense of motion or spinning (vertigo), lightheadedness or feeling faint, unsteadiness or loss of balance, or a feeling of floating, wooziness, or heavy-headedness. Possible causes of dizziness from cancer and its treatment include medications (including, but not limited to, many types of chemotherapy), nausea and vomiting, or anemia. Other potential causes might include high blood pressure, hypoglycemia, dehydration, infection, or stroke.

Tips for coping with dizziness include drinking plenty of fluids, changing positions slowly, walking slowly and carefully, holding handrails up and down stairs, or using a walking device. Reviewing a patient’s medication list for drugs that might cause dizziness and are candidates for discontinuation, is another important strategy.

Our expert clinical pharmacist team remains available 24/7/365 to help identify potential causes of some of those tricky, less common end-of-life symptoms, and to help guide therapy selection (or de-prescribing if appropriate) to manage them. We are ready and eager to assist!

Written by: Jennifer Procaccino, PharmD

References:

1. Jeon YS, Kearney AM, Baker PG. Management of hiccups in palliative care patients. BMJ Supportive & Palliative Care 2018; 8:1-6

2. Steger M, Schneemann M, Fox M. Systemic Review: the pathogenesis and pharmacological treatment of hiccups. Aliment Pharmacol Ther 2015; 42: 1037-1050

3. Anneser J, Arenz V, Borasio G. Neurological Symptoms in Palliative Care Patients. Frontiers in Neurology April 2018; 9:275

4. Lexicomp Online. Wolters Kluwer Health, Inc. Hudson, OH. Available at: http://online.lexi.com. Accessed 10/2020.

5. Palliative Care Network of Wisconsin URL: https://www.mypcnow.org . Accessed 10/2020.

6. Aging Care website. URL: https://www.agingcare.com/articles/loss-of-taste-in-the-elderly-135240.htm . Accessed 10/2020.

7. Cancer Net website. URL: www.cancer.net . Accessed 10/2020.

Lung Cancer Symptom Management at the End of Life

Mon, 04 Jan 2021 18:56:55 GMT

Lung cancer is the second leading cause of all deaths in the United States. It is the second most common type of cancer, but the number one cause of cancer deaths. The primary risk factor, cigarette smoking, is estimated to attribute to 90% of lung cancer cases. This includes cases related to second-hand smoke.

Common symptoms in end-stage lung cancer include dyspnea, cough, and hemoptysis. Additional symptoms include, but are not limited to, wheezing, hoarseness, pain, weight loss, and weakness. We will discuss the more common symptoms and treatment strategies below:

Dyspnea

Dyspnea, also called labored or difficult breathing, is a common symptom in many lung cancer patients. Wheezing is often associated with difficulty breathing. Some potential causes of dyspnea include blocked airways, pleural effusion, and hypoxemia. It is helpful if the cause can be identified, then treatment that targets the cause can be selected.

COPD, asthma, and tumors can lead to blocked airways. Bronchodilators, anticholinergics, and steroids can be used to treat dyspnea associated with COPD, asthma, or tumors that block airways. COPD and asthma patients typically come to hospice on inhalers that may combine some or all of these drug classes. A recent study showed that 45% of COPD patients made at least one error when using their inhalers (Lindh, A. et. al., 2019). We would expect our hospice patients, who are usually weaker and may have multiple comorbidities, to make even more improper-use errors. These errors lead to decreased efficacy and a possible increase in side effects. Inhalers are also very costly. Because of these issues, nebulizers are preferred over inhalers for increased efficacy and a decrease in cost and potential side effects. Addition of oral steroids to the nebulized therapies can provide additional benefits.

The preferred inhaled bronchodilator, anticholinergics, and oral steroids are listed here with usual doses:

Albuterol or ipratropium-albuterol via nebulizer should be scheduled three or four times daily to replace a routine inhaler regimen containing a bronchodilator. A scheduled nebulizer regimen is often preferred for patients experiencing severe dyspnea. Ipratropium can be administered alone for patients who cannot tolerate albuterol.

Mucus or phlegm can also block airways. Guaifenesin is a first-line agent used to thin the mucus so the patient can clear it more effectively. Guaifenesin is available in 600 and 1200 mg Extended Release (ER) tablets dosed every 12 hours. Immediate Release (IR) tablets come in 200 and 400 mg, and liquid is also available. IR formulations are dosed 200 to 400 mg orally every 4 hours as needed for chest congestion. Guaifenesin can also be scheduled if desired.

If pleural effusions are causing dyspnea, they should be drained where appropriate. If hypoxemia is causing dyspnea, supplemental oxygen should be utilized. There are some non-pharmacologic treatments that may also help dyspnea. They include cool air (using a fan, opening windows), relaxation exercises, and meditation.

When a patient experiences refractory dyspnea, opioids are the drugs of choice. Morphine is first-line if not contraindicated. The usual dose for morphine 20 mg/mL oral liquid is 5 mg orally or sublingually every 2 hours as needed for dyspnea. Alternatives include oxycodone IR and hydromorphone IR (tablets preferred; may be crushed). Dyspnea usually responds better with lower doses of opioid given more frequently. However, if a patient is taking many PRN opioid doses for shortness of breath each day, the addition of long-acting opioids may be considered. Long-acting opioids are often helpful if a patient is waking up at night with shortness of breath.

Anxiolytics are used to treat the anxiety that is related to dyspnea. They have no direct effect on dyspnea, so they should not be used alone for shortness of breath. A lorazepam 0.5 mg tab given orally every 4 hours as needed is preferred because it is a less risky alternative than other benzodiazepines due to lack of active metabolites and a shorter duration of action.

Cough

Cough can be a very troublesome symptom in lung cancer. If the underlying cause can be determined, treatment can be targeted to stop or control the cough. Some things that can cause cough are excess mucus, inflammatory secretions, blood in the airways, and tumor infiltration of the bronchus. Some patients will also have an idiopathic cough.

If excess mucus is causing a cough, we want to identify if the cough is productive or non-productive. If the cough is productive, our goal is to thin the mucus so the patient can clear it. Guaifenesin, an expectorant, is our first-line treatment. Dosing was discussed above. If guaifenesin is ineffective, normal saline via nebulizer can be tried to thin secretions. For best results, use normal saline nebulizers 30 minutes after a bronchodilator (albuterol) or anticholinergic (ipratropium) every 4 hours as needed, and it can be scheduled. It is also helpful if the patient is able to drink more fluids to combat excess mucus and to help thin it out.

If the cough is non-productive or the patient is too weak to cough up the excess sputum, anticholinergics like hyoscyamine 0.125 mg orally or sublingually every 4 hours as needed or ipratropium 0.02% via nebulizer every 4 hours as needed can be used.

If cough is suspected to be caused by tumor infiltration of the bronchus or is related to chronic bronchitis, oral steroids can be used. Prednisone or dexamethasone are preferred. Prednisone can sometimes worsen edema; if this occurs, dexamethasone is a better choice. Dexamethasone is also used if the patient has a brain tumor, as dexamethasone penetrates the blood-brain barrier and helps treat inflammation associated with the brain tumor. The starting dose for prednisone is typically 10 mg orally every morning, and for dexamethasone, it is 2 mg orally every morning.

Cough suppressants are used to control the severity of the cough. Guaifenesin-dextromethorphan 100-10 mg/5 mL can be given as 10 mL orally every 4 hours as needed for cough. If this is not effective, an opioid can be added. Guaifenesin-codeine 100-10 mg/5 mL can be given as 10 mL orally every 4 hours as needed, or hydrocodone-homatropine 5-1.5 mg/5 mL can be given as 5 mL orally every 4-6 hours as needed.

For patients having trouble sleeping because the cough is waking them up at night, longer-acting cough suppressants can be tried. A couple of common ones: benzonatate 100-200 mg orally three times daily as needed, or dextromethorphan 30 mg/5 mL ER liquid given as 10 mL orally every 12 hours as needed for cough.

For idiopathic refractory cough, gabapentin has been used successfully. Note that cough is an off-label use of gabapentin. The starting dose is 300 mg orally at bedtime. If this dose is not effective it may be increased in increments of 300 mg once or twice daily. If needed, further increases can be made gradually up to 900 mg twice daily, while closely evaluating effect and tolerability.

Hemoptysis

Hemoptysis, or blood in the bronchial secretions, occurs in about 20% of lung cancer patients. Pulmonary hemorrhage occurs in around 3% of patients and, unfortunately, often ends in death. Some possible causes of hemoptysis are anticoagulation therapy, pulmonary embolism, and bronchiectasis.

Treatment of hemoptysis includes cough suppressants (discussed above) and discontinuing anticoagulant/antiplatelet agents. Additional measures to minimize the impact of hemoptysis might include positioning the patient to prevent choking, utilizing dark colored bed linens, and the use of anxiolytics, such as lorazepam.

In conclusion, for patients with dyspnea and cough, identify the underlying cause if possible. This will guide better treatment selection. Steroids can be used to treat a variety of conditions when appropriate, thus minimizing pill burden. Nebulizers, with or without steroids, are preferred over inhalers in most hospice patients due to inadequate inhaler technique, inability to take a deep breath, and possible increase in side effects. Anxiolytics should not be used alone for dyspnea. They have no direct effect on dyspnea, but do help reduce the anxiety that can exacerbate dyspnea. Opioids may be used concurrently with other therapies to manage refractory dyspnea.

Consult your ProCare Clinical Pharmacist team any time, 24/7/365, to help manage lung cancer symptoms. We can identify alternative patient-specific therapies to help patients breathe easier while keeping your medication costs lower!

Written by: Karen Bruestle-Wallace, PharmD.

References

1. American Cancer Society (2018). Lung Cancer- Non-Small Cell: Statistics. Net. https://www.cancer.net/cancer-types/lung-cancer-non-small-cell/statistics

2. Siddiqui, F.; Siddiqui, H. (2020). Lung Cancer StatPearls. NCBI Bookshelf. https://www.ncbi.nlm.nih.gov/books/NBK482357/

3. Lim, R. B. (2016). End-of-life care in patients with advanced lung cancer. Therapeutic Advances in Respiratory Disease,10(5), 455-467. doi:10.1177/1753465816660925

4. Farbicka, P., & Nowicki, A. (2013). Reviews Palliative care in patients with lung cancer. Współczesna Onkologia,3, 238-245. doi:10.5114/wo.2013.35033

5. Lexicomp Online, Lexi-Drugs Online, Hudson, Ohio: Lexi-Comp, Inc.; October 20, 2020.

6. Lindh, A., Theander, K., Arne, M., Lisspers, K., Lundh, L., Sandelowsky, H., . . . Zakrisson, A. (2019). Errors in inhaler use related to devices and to inhalation technique among patients with chronic obstructive pulmonary disease in primary health care. Nursing Open,6(4), 1519-1527. doi:10.1002/nop2.357

7. Razzak, R., Waldfogel, J. M., Doberman, D. J., Feliciano, J. L., & Smith, T. J. (2017). Gabapentin for Cough in Cancer. Journal of Pain & Palliative Care Pharmacotherapy,31(3-4), 195-197. doi:10.1080/15360288.2017.1420120

Hospice Awareness Month

Fri, 13 Nov 2020 18:52:37 GMT

Celebrating Hospice Awareness Month with a virtual standing ovation for our valued hospice partners!

“You matter because you are you, and you matter to the end of your life. We will do all we can, not only to help you die peacefully, but also to live until you die.”

- Dame Cicely Saunders

While this year has presented many obstacles to the hospice care we know and love, hospice clinicians all over the world have embraced the challenges, and have emerged stronger and more passionate for their cause than ever before. We commend the nurses, doctors, nurse practitioners, nurse’s aides, social workers, spiritual care, volunteers, and all others who work tirelessly to provide the same superlative care that Dame Cicely Saunders strove to achieve at St. Christopher’s hospice many years ago.

When our ProCare HospiceCare pharmacist team was asked to describe hospice in a few words, we immediately thought of: compassion, humanity, kindness, dignity and strength. We appreciate the supporting role we play as we interact daily with nurses, providing clinically appropriate and cost effective medication recommendations. The dedication of the holistic hospice team directly leads to patients/families achieving their unique goals at end of life.

From our team to yours, thank you from the bottom of our hearts for all you do to help patients live until they die.

Palliative Sedation in Hospice Care

Thu, 05 Nov 2020 18:49:42 GMT

The word "sedation" is of Latin derivation, with sedare meaning "to settle, to calm" in Latin. Use of the word transferred to the English language (from the French sedation) in the mid-16th century but did not become a commonly used term until about 1950. Since then, various forms of sedation have found clinical use, from temporary sedation for clinical procedures to palliative sedation to manage distressing symptoms at end-of-life, to name just two examples.

Palliative sedation (PS) is defined as the lowering of a dying patient’s consciousness using sedative medications with the intent of limiting patient awareness of intractable and intolerable suffering. Suffering encompasses the broad range of injuries or threats to one’s being (i.e. physical, psychosocial, spiritual, temporal, and existential). Intractable suffering is suffering that has not adequately responded to all trialed interventions and for which additional interventions are either unavailable or impractical; this may also be described as refractory suffering that cannot be adequately controlled despite aggressive efforts to identify therapy that does not compromise consciousness. Intolerable suffering is suffering that is “unbearable,” as described by the patient and verified by the patient’s interdisciplinary team. When a patient is unable to communicate, the family should consider whether, based on the known values and wishes of the patient, suffering has reached a level that the patient would declare as intolerable.

The use of PS in appropriate cases has been repeatedly upheld by the courts, but, as with any treatment, careful ethical consideration by qualified clinicians is necessary. The goal of PS is to decrease suffering but not to kill or hasten death. Euthanasia shares the same goal of decreasing suffering but differs in its intent (to end life), its process (administration of a lethal drug dose), and its immediate outcome (death). Assessment of core ethical principles assists clinicians in determining if PS is appropriate for a given patient. The National Hospice and Palliative Care Organization (NHPCO), American Academy of Hospice and Palliative Medicine (AAHPM), and Hospice & Palliative Nurses Association (HPNA), among other organizations, have issued position statements that may assist clinicians in determining if PS is appropriate.

The two most common indications for PS are delirium and dyspnea, but PS has been used to successfully manage myriad other symptoms, as well (e.g. pain, vomiting, itching, bleeding, psychological distress, seizures, malaise, panic, clots, fecal retention, etc.). “Proportional sedation,” where sedation is titrated to the minimal level of sedation that permits the patient to tolerate the unbearable symptom(s), is the most commonly used approach today, versus deeper sedation practices that had been used more in the past. Another potential option is “respite sedation” (also known as “intermittent sedation”), where consciousness is reduced for predetermined periods followed by periods of wakefulness. This “respite sedation” is accomplished by reducing or discontinuing the sedative and may reveal if the distress (especially psychological or existential) can be resolved by “breaking the cycle” of fear, fatigue, or insomnia near end-of-life.

Figure: Checklist in Preparation for Palliative (Adapted from National Hospice and Palliative Care Organization (NHPCO) Position Statement 2010.)

Terminal illness with refractory and intolerable symptoms verified
Exhaustion of all other feasible palliative care treatments (and documented as such)
Consideration of psychiatric, ethical, and spiritual consultations
Do-not-resuscitate (DNR) order in place
Determination regarding discontinuation of nutritional and hydration support in patients receiving such treatments
Informed consent
Selection of most appropriate and cost-effective sedative(s)
Consideration of a trial of respite sedation, if appropriate

An important aspect of a PS plan is the selection of the appropriate sedative(s) to achieve the appropriate level of sedation. The three most commonly used classes of “primary sedatives” are benzodiazepines (such as lorazepam, diazepam, or midazolam), barbiturates (such as phenobarbital), and anesthetics (such as propofol). Midazolam, in its injectable form, is the most commonly used agent in the hospital setting, and lorazepam is the most commonly used agent in the home and nursing home settings. Nasal midazolam has also been used, but the cost may be prohibitive. Phenobarbital may be particularly beneficial when benzodiazepines are ineffective or not well tolerated. Propofol has been the subject of increased scrutiny and is generally reserved for refractory cases in the inpatient setting. Agents such as opioids, antipsychotics, and the anesthetic ketamine are considered “adjunctive sedatives” and are generally added in addition to one of the aforementioned sedatives to manage certain symptoms (but not generally utilized as the sole agent to achieve PS).

In the rare circumstance that palliative sedation is being considered, remember you have a team of hospice and palliative expert pharmacists available 24/7/365. They can help review for any possible remaining therapies or regimens to manage distressing and intolerable symptoms or pain and review for any obstacles potentially reducing the efficacy of current treatments. If every option has been exhausted, a ProCare HospiceCare hospice and palliative pharmacist can help guide medication selection and appropriate dosing for palliative sedation.

Written by: Brett Gillis, Pharm.D., R.Ph.

References:

1. American Academy of Hospice and Palliative Medicine (AAHMP). Position Statement 2014.

2. Bodnar J. A review of agents for palliative sedation/continuous deep sedation. J of Pain & Pall Care 2017;31(1):16-37.

3. Hahn M. Review of palliative sedation and its distinction from euthanasia and lethal injection. J of Pain & Pall Care 2012;26(1):30-39.

4. Hospice & Palliative Nurses Association (HPNA). Position Statement 2016.

5. Maltoni M, et al. Palliative sedation in patients with cancer. Ca Contr 2015;22(4):433-441.

6. Narula P. Palliative sedation. ProCare 2016.

7. National Hospice and Palliative Care Organization (NHPCO). Position Statement 2010.

8. Patel C, et al. Palliative sedation: a safety net for the relief of refractory and intolerable symptoms at the end of life. AJGP 2019;48(12):838-845.

9. Twycross R. Reflections on palliative sedation. Pall Care: Res and Treat 2019;1-16.

Non-Traditional Symptom Management in Hospice and Palliative Care: Aromatherapy and Music

Tue, 08 Sep 2020 17:46:45 GMT

In hospice and palliative care, we sometimes need to consider complementary and alternative (CAM) therapies. One reason might be that the more “traditional” medication therapies are not effective, despite dose optimization, or a given patient has issues with drug allergies, interactions, and/or adverse effects. Or sometimes, patients and caregivers may desire complementary therapies. In a study that took place in a palliative IPU, 82% of the patients surveyed were interested in trying CAM therapies, with the greatest interest expressed in music therapy (61% of patients) and massage therapy (58% of patients). In this same study, 100% of “substitute decision makers” expressed an interest in having CAM therapies available for their loved ones to try.¹ Furthermore, aromatherapy and music therapy typically have a favorable benefit-to-risk ratio, although every patient is unique and should be evaluated individually.

Aromatherapy

When using aromatherapy oils, it is important to use high-quality, 100% pure and genuine essential oils from a reputable supplier or manufacturer that analyzes their oils. Aromatherapy products should typically be used in areas of good ventilation. Keep in mind that they are highly flammable – so they would not be safe or appropriate in patients who use oxygen therapy. Additional information on aromatherapy safety and basic principles can be found on the National Association for Holistic Aromatherapy website at www.naha.org .

One area of application for aromatherapy is nausea. An interesting study took place in an emergency department (ED), comparing inhalation of the fumes from topical antiseptic isopropyl alcohol (IPA) to oral ondansetron.² Patients who came into the ED with nausea were randomized into one of three interventions:

IPA inhalation + ondansetron 4mg by mouth; OR
IPA inhalation + placebo by mouth; OR
Inhaled placebo + ondansetron 4mg by mouth

The patients reported their nausea scores using a 100mm visual analog scale at baseline and at 10, 20, 30, and 60 minutes after the intervention, and then every 60 minutes until ED disposition (i.e. admission to hospital or discharge home). They were allowed to take another inhalation at each measurement.

Patient results were grouped based on how long they stayed in the ED. Graph A shows results for patients in the ED less than 120 minutes. Up to the 30 minute mark, IPA inhalation groups (with or without oral ondansetron) saw significant improvement in their nausea scores. The group receiving oral ondansetron alone did not see any improvement within 30 minutes. After 30 minutes, those receiving oral ondansetron (with or without IPA) showed a greater drop in nausea scores than those receiving IPA inhalation alone.

Mean nausea VAS scores from study administration until ED disposition, for patients with ED disposition less than 120 minutes. From April MD, et al.

Graph C below shows results for patients in the ED less than 240 minutes. Results before the 30 minute mark are similar to those in Graph A, but results after the 30 minute mark are more apparent in Graph C. Similar to the group above, this graph shows how both oral ondansetron groups (with or without inhaled IPA) continue to have significant reductions in their nausea scores between 30 and 60 minutes, while the effects of using IPA inhalation alone leveled off after 30 minutes. This could be attributed to the 30-minute onset of action for oral ondansetron. However, despite the significant nausea score reduction after 30 minutes for participants receiving ondansetron, those receiving ondansetron alone still never reach the same total nausea score reduction as those receiving IPA.

The takeaway: it appears IPA inhalation alone or in combination with oral ondansetron was more effective than oral ondansetron alone at all measurement points. Additionally, IPA inhalation seemed to produce earlier benefits and “boost” the total effectiveness of oral ondansetron.

Mean nausea VAS scores from study administration until ED disposition, for patients with ED disposition less than 240 minutes. From April MD, et al.

Music

The American Music Therapy Association defines music therapy as: “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.” Another term sometimes used in the literature is “music medicine,” which involves prerecorded music administered by medical or healthcare staff and preselected by study investigators, who may or may not have any formal training in music therapy. Based on the evidence, both approaches appear to be effective in certain situations.

It appears that music is effective for pain, anxiety, and depression because it impacts areas of the brain that are rich in receptors for endogenous opioids and dopamine. Music’s effects on pain are demonstrated by a study that took place in a burn unit.³ Patients chose from 10 pieces of recorded non-lyrical instrumental music that they listened to for 30 minutes before and after their dressing changes; the study found that patient-selected music plus standard treatment reduced pain during the dressing changes. This study also found that while the overall frequency of analgesic use was not reduced, the type of analgesics used changed – there was a significant decrease in use of opioids, but an increase in use of non-opioids (e.g. acetaminophen, NSAIDs), which the authors attribute to lower levels of pain perception.

Illustration of the areas of the brain affected by music, and implicated in the pathophysiology of pain, anxiety, and/or depression. From Archie P, Bruera E, Cohen L.

In many situations, it is preferred for patients to listen to music via headphones – in the study just mentioned, headphones were used specifically to help block out the sounds of the burn unit. However, headphones are contraindicated in situations where the patient needs to hear the comments or directions of the medical team, because wearing headphones may make it difficult for the patient to hear these directions, which can increase the patient’s anxiety and in turn increase their perceived pain.

Aromatherapy and Music: Viable Adjunctive Therapies

As can be seen here, there are studies that seem to support the effectiveness of aromatherapy and music for certain symptoms in hospice and palliative care, although overall, a greater number and rigor of studies are needed. These therapies generally seem to be most effective as add-on measures to more traditional and/or medication therapies and are worth considering in a variety of patient situations.

Written by: Joelle Potts, PharmD, BCGP

References:

1. Grief CJ, Grossman D, Rootenberg M, Mah L. Attitudes of terminally ill older adults toward complementary and alternative medicine therapies. J Palliat Care. 2013 Winter; 29(4): 205-9. [Abstract]

2. April MD, et al. Aromatherapy versus oral ondansetron for antiemetic therapy among adult emergency department patients: a randomized controlled trial. Annals of Emergency Medicine. 2018 Aug; 72(2): 184-93. Epub 2018 Feb 17.

3. Rohilla L, Agnihotri M, Trehan SK, Sharma RK, Ghai S. Effect of music therapy on pain perception, anxiety, and opioid use during dressing change among patients with burns in India: a quasi-experimental, cross-over pilot study. Ostomy Wound Management, 64(10), October 2018. 40-46. Available at: https://www.o-wm.com/article/effect-music-therapy-pain-perception-anxiety-and-opioid-use-during-dressing-change-among [last accessed 7/9/2020]

Additional References:

4. Deng G, Cassileth BR. Complementary therapies in pain management. Chapter in: Oxford Textbook of Palliative Medicine; 5th Edition, 2015. Editors: Cherny NI, Fallon MT, Kaasa S, Portenoy RK, Currow DC; Oxford University Press, Oxford, United Kingdom. 628-31.Grief CJ, Grossman D, Rootenberg M, Mah L. Attitudes of terminally ill older adults toward complementary and alternative medicine therapies. J Palliat Care. 2013 Winter; 29(4): 205-9. [Abstract]

5. Alliance of International Aromatherapists (AIA) website: www.alliance-aromatherapists.org [last accessed 7/31/2020]

6. National Association for Holistic Aromatherapy (NAHA) website: naha.org [last accessed 7/31/2020]

7. Ondansetron. Lexicomp (Lexi-Drugs) online. Wolters Kluwer, copyright UpToDate, Inc.; last updated 7/23/2020. [last accessed 7/31/2020]

8. American Music Therapy Association website: www.musictherapy.org [last accessed 6/27/2020]

9. Archie P, Bruera E, Cohen L. Music-based interventions in palliative care: a review of quantitative studies and neurobiological literature. Support Care Cancer. 2013; 21: 2609-24.

10. Bradt J, Dileo C, Magill L, Teague A. Music interventions for improving psychological and physical outcomes in cancer patients. Cochrane Database of Systematic Reviews. 2016, Issue 8. Art. No.: CD006911.

Cost Effective Pain and Symptom Management in the Hospice Patient

Mon, 17 Aug 2020 17:37:35 GMT

Exceptional pain and symptom management is an essential component of hospice care. Hospice clinicians must consider cost-management in addition to therapeutic appropriateness when choosing medications for their patients at the end-of-life. This article will focus on common end-of-life symptoms seen in the hospice setting, including pain, anxiety and agitation, nausea and vomiting, constipation, dyspnea, and terminal secretions and how to cost-effectively manage these symptoms.

Pain Management

When assessing the patient’s pain, there are certain patient factors that should be evaluated. The patient’s diagnosis, allergies, renal and hepatic function, and swallowing status can all affect which medication to choose. The type of pain that the patient is experiencing will also impact choice of medication. Common types of pain seen in the hospice setting are nociceptive pain and neuropathic pain. For mild to moderate nociceptive pain, acetaminophen and NSAIDs are usually first-line. Opioids are typically utilized for moderate to severe pain, with morphine being generally regarded as the most cost-effective short-acting opioid. Other short-acting opioids often used in the hospice setting include oxycodone and hydromorphone. For a patient who requires long-acting pain control, an extended-release opioid can be effective. Morphine ER and methadone are typically the most cost-effective long-acting opioids available. Notably, methadone is effective for neuropathic pain and can be administered via many routes to a patient who cannot swallow. However, because of its unique pharmacokinetic profile, methadone must always be dosed by an experienced clinician and under close supervision. Other adjuvants for pain management in the hospice patient include oral corticosteroids, gabapentin, and tricyclic antidepressants.

Anxiety, Agitation, Terminal Restlessness

When assessing an anxious or agitated patient, it is important to first determine if there are any underlying issues that may be causing the patient’s change in behaviors. Is the patient in uncontrolled pain? Is there an underlying infection that is causing the patient to be restless or confused? Are the patient’s bowels moving? Benzodiazepines are typically used as first-line to treat anxiety or agitation, with lorazepam being the most cost-effective option. Antipsychotics can be used if benzodiazepines are ineffective. Haloperidol is typically the most cost-effective medication in this class, and quetiapine is the most preferred cost-effective option in patients with Parkinson’s disease. For severe anxiety or agitation, medications like divalproex or phenobarbital can be effective.

Nausea & Vomiting

For patients complaining of nausea/vomiting, it is important to try to identify the most likely trigger for the nausea. Several different neurotransmitters and receptors are involved in the emetic pathway, and targeting these receptors can help select which antiemetic agent to utilize. The table below summarizes which treatments are available:

$$ Tier 2

$$$ Tier 3

Bowel Management

Constipation is the most common adverse effect occurring with chronic opioid use. Since many hospice patients are utilizing opioids, whether scheduled or on an as needed basis, prophylactic treatment for constipation using a stimulant laxative should be part of the patient’s regimen. First-line stimulant laxative treatment is typically senna, or senna with docusate. An osmotic laxative can be added as a second-line agent, with sorbitol being a more cost-effective option than lactulose. Polyethylene glycol is also a cost-effective osmotic laxative, and is often recommended in cancer guidelines, but the fluid volume may be difficult to swallow for patients with dysphagia.

Dyspnea, Shortness of Breath

Difficulty breathing often occurs at the end-of-life, especially in patients with end-stage lung disease. Patients may complain of feeling short of breath, and their respiratory rates often reflect the feeling of breathlessness. Opioids are typically a mainstay of treatment of dyspnea at end of life, with morphine being the most cost-effective choice. Many patients may request to continue to use their inhaler devices, such as metered-dose inhalers or dry powder inhalers. These devices require manual dexterity, coordination, and deep inhalation. Most hospice patients are too weak or lack coordination to perform the necessary functions to use these devices appropriately. Additionally, the costs of these inhaler devices can be hundreds of dollars per device. For these reasons, it is preferred to use alternatives such as albuterol or ipratropium via a nebulizer. Oral corticosteroids can also be beneficial for dyspnea when inhaled therapies alone are not fully effective.

Terminal Secretions

Also known as “death rattle” or “terminal congestion”, terminal secretions often occur within the last few hours of life. Although these secretions are not disturbing to the patient, caregivers and family members hearing this noise often perceive the patient to be in distress and request treatment. Hyoscyamine and atropine drops are often chosen as first-line agents due to their cost and quick onset of action. It is important to remember that data to support the use of any antisecretory agent is limited, so supportive care and family education is essential.

Your ProCare clinical pharmacists are experts in pain and symptom management strategies that are cost-effective and patient-specific. We are available 24/7/365. Please contact us if you would like recommendations for your patient care needs!

Written by: Kiran Hamid, R.Ph.

References

Lexicomp Drug Database. Available by subscription only from: online.lexi.com.
Twycross R, Wilcock A, eds. Hospice and Palliative Care Formulary USA. Nottingham, UK: Palliativedrugs.com Ltd; 2006.
Watson, J. (2018, October). Nociceptive Pain. Retrieved from https://www.merckmanuals.com/home/brain,-spinal-cord,-and-nerve-disorders/pain/nociceptive-pain
World Health Organization Pain Ladder for Adults. http://www.who.int/cancer/palliative/painladder/en/
Osvaldo, Jose. (2015, March). Revisiting methadone: pharmacokinetics, pharmacodynamics and clinical indications. Retrieved from http://www.scielo.br/scielo.php?script=sci_arttext&pid=S1806-00132015000100060
Palliative Pharmacy Care. JM Strickland. Agitation and Delirium. Pgs. 77-89. American Society of Health-System Pharmacists. Bethesda, MD. 2009.
Marschke, M. Dementia, Delirium, Depression and Anxiety at End of Life. Available at: www.amsa.org/dd/Depression.ppt. Accessed Jan 17, 2011.
Glare, P. et al. (2011, September). Treating nausea and vomiting in palliative care: a review. Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3180521/
McPherson ML. (2018, February). Management of Opioid-Induced Constipation in Hospice Patients. Retrieved from https://www.ncbi.nlm.nih.gov/pubmed/28423917
Ross, D. et al. (2001, September). Management of Common Symptoms in Terminally Ill Patients: Part II. Constipation, Delirium and Dyspnea. Retrieved from https://www.aafp.org/afp/2001/0915/p1019.html#afp20010915p1019-t4https://www.ncbi.nlm.nih.gov/pmc/articles/PMC155633/
Clark, L. (2011, January). Risky Business: Anticoagulation Therapy in the Setting of Hospice and Palliative Care. Retrieved from https://www.jpsmjournal.com/article/S0885-3924(10)00861-4/fulltext
Fahrni J, Husmann M, Gretener SB, Keo HH. Assessing the risk of recurrent venous thromboembolism--a practical approach. Vasc Health Risk Manag. 2015;11:451–459. Published 2015 Aug 17. doi:10.2147/VHRM.S83718
Madison, M. (2015). Managing Complex Symptoms in End of Life Care[PowerPoint slides].
Davis, Caralyn. (2020, March). COVID-19 Not in Your Building? 10 Keys to Limiting Spread and Impact. Retrieved from https://www.aadns-ltc.org/Resources/details/post/covid-19-not-in-your-building-10-keys-to-limiting-spread-and-impact/2020-03-25 .
Amirav, I. (2020, March). Transmission of Corona Virus by Nebulizer- a serious, underappreciated risk! Retrieved from https://www.cmaj.ca/content/re-transmission-corona-virus-nebulizer-serious-underappreciated-risk .

Deprescribing and Optimizing Medication Use

Mon, 06 Jul 2020 17:33:40 GMT

The Lown Institute has identified medication overload, or polypharmacy, as a threat to the future of our healthcare system. Researchers found that almost 20% of older adults take 10 or more medications per day. The more medications a patient takes, the greater the risk of complications. The US is on track to spend $62 billion on hospitalizations due to adverse drug events over the next 10 years. The good news is that hospice and palliative care clinicians are uniquely positioned to be part of the solution. Nurses and physicians can emphasize the importance of medication reviews and deprescribing to patients and families to stop these projections from becoming statistics.

Deprescribing

Deprescribing is the systematic process of identifying and discontinuing medications based on the patient’s prognosis and specific goals of care. This practice is most helpful with a life expectancy of a year or less, or when an adverse medication effect is suspected. For best results, it is recommended to take a step-wise approach to deprescribing:

Start with a comprehensive list of medications; ideally upon admission
Identify potential medications to be tapered off and/or discontinued
Develop a plan for tapering and/or discontinuation of targeted medications
Monitor closely for withdrawal symptoms

When a patient’s Palliative Performance Score (PPS) drops below 40%, it is reasonable to begin discontinuing unnecessary medications. The most commonly discontinued medication classes include, but are not limited to statins, multivitamins/supplements, proton pump inhibitors, thyroid medications, respiratory inhalers, anti-hypertensives, anticoagulants, anti-depressants, and dementia medications. With chronic medication use, patients become physically and emotionally attached. It is helpful to have supporting information when discussing deprescribing plans with patients/families. Below are a few medication types and supporting information for discontinuation:

Medication Optimization

In hospice and palliative care, the goals of care shift from curative to comfort through symptom control.

Below are several strategies to aid in optimizing a patient’s medication regimen at end-of-life:

Review medication list and determine what is reasonable and necessary to continue for symptom management related to the terminal illness and related conditions, per CMS §418.200 Conditions of Participation⁵
Is atorvastatin for cholesterol reasonable and necessary for symptoms in lung cancer?
Individual patient assessment
Examine your patient’s Palliative Performance Score, swallowing ability, appetite, etc.
Plan ahead and use anticipatory prescribing
Utilize standing orders and comfort care kits
Use routine and PRN orders to control symptoms more effectively
Ex: Morphine ER for long-acting pain relief and Morphine IR for breakthrough pain
Minimize pill burden through use of medications that treat multiple systems
Ex: Prednisone for pain, inflammation, appetite, and energy
Continually review and monitor symptom medications for effectiveness
Ask the following: Is this still the right medication? The right dose? Is the indication still appropriate?

The overall goal of medication review is to ensure the patient has the best quality of life possible in their remaining days. At the end of the day, our patients are more than just a medication list; they each have unique and important goals of care. Hospice clinicians are well-positioned to advocate for their patients’ best interests and cater to those goals to create a lasting impact when it counts the most.

For more information, check out these tools/criteria for medication review:

Deprescribing: www.deprescribing.org

Beers Criteria: https://bit.ly/2GQhM2Y

START/STOPP: https://www.herefordshireccg.nhs.uk/your-services/medicines-optimisation/prescribing-guidelines/deprescribing/748-stopp-start-herefordshire-october-2016/file

Medication Appropriateness Index: https://41e5fc1d-e404-4830-8c07-64690e79acce.filesusr.com/ugd/2a1cfa_92f7abde530844aaa6bd44ac57a413b3.pdf

Good Palliative Geriatric Practice Algorithm: https://www.researchgate.net/figure/The-Good-Palliative-Geriatric-Practice-GPGP-algorithm-D-Garfinkel-S-Zur-Gil-J_fig3_304143731

Written by: Meri Madison, PharmD, RPh

References

1. Lown Institute. Medication overload and older Americans. Available from: https://lowninstitute.org/projects/medication-overload-how-the-drive-to-prescribe-is-harming-older-americans/ .

2. Endsley, S. Deprescribing Unnecessary Medications: A Four-Part Process. Fam Pract Manag. 2018;25 (3):28-32.

3. Thompson J. Deprescribing in palliative care. Clinical Medicine 2019 Vol 19. No 4: 311-14.

4. Kim LD, Factora RM. Alzheimer’s dementia: Starting, stopping drug therapy. Cleveland Clinic Journal of Medicine March 2018, 85 (3) 209-214; Available from: https://doi.org/10.3949/ccjm.85a.16080 .

5. Electronic Code of Federal Regulations. Part 418 Hospice Care. Available from: https://www.ecfr.gov/cgi-bin/text-idx?SID=1e60a115cd2f086b2c32af0cce72353d&mc=true&node=pt42.3.418&rgn=div5#se42.3.418_154 .

6. Van Den Noortgate, Nele J. et al. Prescription and Deprescription of Medication During the Last 48 Hours of Life: Multicenter Study in 23 Acute Geriatric Wards in Flanders, Belgium. Journal of Pain and Symptom Management, Volume 51, Issue 6, 1020 – 1026.

7. Todd, Adam, and Holly M. Holmes. “Recommendations to Support Deprescribing Medications Late in Life.” International journal of clinical pharmacy 37.5 (2015): 678–681. PMC. Web. 2 Aug. 2018.

8. Pruskowski, J. Fast Facts and Concepts #321 Deprescribing. Available from: https://www.mypcnow.org/copy-of-fast-fact-320 . Accessed 2 August 2018.

Managing Opioids for Pain and Opioid-Induced Hyperalgesia in an Opioid Crisis Society

Fri, 05 Jun 2020 17:24:28 GMT

In the US, drug overdose is the leading cause of death for persons under age 50, and those between ages 18-25 are the most likely to use addictive drugs. Nine out of 10 people with substance problems started using by age 18. Those aged 18-25 years with substance use disorder (SUD) report getting 37.5% of their opioids from a friend or relative for free, and 19.9% report getting them from a friend or relative that they pay.

The previous statistics illustrate the importance of maintaining tight control on opioids in order to help fight the opioid crisis. It is important to identify patients and families at risk of opioid misuse or diversion (see Table 1). Additional steps can then be taken to ensure opioids are kept out of the wrong hands.

Screening and assessment tools are not specific to hospice patients. They can be used as they are, or as a resource for designing your own tools and questions. The Opioid Risk Tool(ORT) https://www.drugabuse.gov/sites/default/files/files/OpioidRiskTool.pdf is designed to be used before starting long-term opioid therapy. Positive responses are weighted and added up to indicate the patient’s risk for opioid abuse. The Addiction Behaviors Checklist (ABC) is a tool that can be used for patients currently taking opioids https://www.nhms.org/sites/default/files/Pdfs/Addiction_Behaviors_Checklist-2.pdf . It examines addiction behaviors during each provider visit, and behaviors since the last visit. A score of 3 or greater indicates possible opioid misuse. Further evaluation, closer monitoring and increased accountability measures may be needed for patients scoring 3 or above.

Pain Management Agreements or Treatment Agreements are a good way to promote understanding regarding the patient's and hospice’s roles and responsibilities surrounding opioids and other controlled substances. They should facilitate communication and involve caregivers and family members if appropriate.

Opioid-Induced Hyperalgesia (OIH) is a complication of opioid use and abuse that is just starting to be recognized clinically. It is more common with high dose opioids, though it can occur even in patients who are opioid naïve. It can also occur in patients with a history of opioid abuse. OIH occurs in acute and chronic pain, and also in malignant and non-malignant conditions. Fentanyl and morphine are the opioids with greatest risk, but OIH is also reported with high dose oxycodone.

In order to diagnose OIH, confounding factors must be ruled out. These include tolerance, disease progression, withdrawal hyperalgesia, pain unresponsive to opioid therapy, and opioid-induced androgen deficiency. Signs of OIH include an increase in pain sensitivity, worsening pain with increased opioid dose, sensitivity to painful, as well as non-painful, stimuli, and diffuse pain.

There are different options to manage OIH. In rapid dose reduction, the opioid is decreased by 20-50% the first day, then 10-20% every day depending on patient response and goals of therapy. The dose can also be decreased by 40-50% and low dose (adjunct) methadone can be added if appropriate, as it is known to work differently from other opioids, and can reduce OIH. Opioid rotation is also an option. If the patient is on morphine or hydromorphone, they potentially could be rotated to methadone or fentanyl, if not contraindicated. Methadone may be appropriate and effective for some patients. The off-label use of low dose ketamine (a non-opioid medication) and a reduction in the opioid dose shows promise as another way to manage OIH. Both Methadone and Ketamine can be given by many different routes; the oral route is most convenient for hospice patients. Dosing and titration is complex and based on individual patient factors. Coordination with the patient’s medical provider is critical and a ProCare pharmacist can provide information to facilitate your decision about whether methadone and/or ketamine would be appropriate.

Other non-opioid analgesics or adjuvants should also be utilized for pain that is unresponsive to opioids (though methadone can be an exception, as this opioid is effective for neuropathic pain where other opioids are not). See Table 2.

In summary, procedures need to be in place to identify patients at risk for opioid misuse, patients who are misusing opioids, and environments at risk for drug diversion. Treatment agreements and appropriate controls need to be in place to help control the opioid crisis. And if a patient’s pain is not being managed well with opioids, clinicians needs to assess for possible OIH vs other challenges or confounders.

Please contact a ProCare Clinical Pharmacist, 24/7, for guidance on how to manage suspected or confirmed opioid abuse or symptoms of OIH.

Written by: Karen Bruestle-Wallace, Pharm D, BCGP

References:

(DHHS/PHS), S. A. and M. H. S. A. (2012). Managing Chronic Pain in Adults with or in Recovery from Substance Use Disorders. Treatment Improvement Protocol (TIP) Series 54. Substance Abuse and Mental Health Services Administration. https://doi.org/(SMA) 12-4671
Carullo, V., Fitz-James, I., & Delphin, E. (2015). Opioid-induced hyperalgesia: A diagnostic dilemma. Journal of Pain and Palliative Care Pharmacotherapy, 29(4), 378–384. https://doi.org/10.3109/15360288.2015.1082006
Cheattle, M. D. (2019). Risk Assessment: Safe Opioid Prescribing Tools. Retrieved February 24, 2020, from PPM Practical Pain Management website: https://www.practicalpainmanagement.com/resource-centers/opioid-prescribing-monitoring/risk-assessment-safe-opioid-prescribing-tools
Kaplan, S. (2017). C.D.C. Reports a Record Jump in Drug Overdose Deaths Last Year - The New York Times. Retrieved February 23, 2020, from The New York Times website: https://www.nytimes.com/2017/11/03/health/deaths-drug-overdose-cdc.html
Key Ph.D., K. (2017). Drug Overdoses are Leading Cause of Death for those under 50 | Psychology Today. Retrieved February 23, 2020, from Psychology Today website: https://www.psychologytoday.com/us/blog/counseling-keys/201711/drug-overdoses-are-leading-cause-death-those-under-50
Nathan, Y. (2019). Addiction Statistics - Facts on Drug and Alcohol Use - Addiction Center. Retrieved February 23, 2020, from https://www.addictioncenter.com/addiction/addiction-statistics/
ProCare HospiceCare. (2016). Ketamine Use – Quick Guide. Gainesville, GA.
US Department of Veterans Affairs. (2016). Opioid Taper Decision Tool. 1–16. Retrieved from https://vaww.portal2.va.gov/sites/ad/SitePages/Home.aspx
Wall, J., & Chauhan, A. (2018). A Case of Opioid-Induced Hyperalgesia. Journal of Pain and Palliative Care Pharmacotherapy, 32(2–3), 158–160. https://doi.org/10.1080/15360288.2018.1546256

COVID19 Symptom Management in Hospice – Top 5 Evidence-Based Tips

Mon, 04 May 2020 22:41:34 GMT

1. Inhalers with valved holding chambers (VHCs): use over nebulizers if clinically appropriate for your hospice patients with confirmed or suspected COVID-19.

A number of hospice COVID19 cases will still be more appropriate for nebs (e.g. if patient has severe, life-threatening respiratory symptoms, or is unable to use a chamber). The recommendations to prefer inhalers with VHCs over nebulizers is to reduce the amount of potentially infectious aerosol dispelled into the air during nebulization.¹

2. NSAIDs: use when clinically appropriate.

The WHO and FDA do not recommend against use of NSAIDs at this time, as there is not enough information to recommend against their use.² ³

News reports had echoed a March 11, 2020 letter⁴ in the Lancet Medical journal suggesting that a particular enzyme (ACE2) is increased by NSAIDs, which could aggravate COVID-19 symptoms. NSAIDs are known to reduce inflammation and mask fevers, but no evidence that they worsen symptoms related to COVID-19 has been demonstrated thus far. However, for other reasons, such as renal impairment, cardiovascular disease and bleeding history, NSAIDs may not be appropriate in many hospice patients.

3 . Oral Steroids: for hospice patients in particular, use when clinically appropriate.

In hospice patients with COVID-19, consider continued use of oral steroids if there is some other indication or condition supporting their use. It's likely ok to add them for acute symptom management of breathlessness, as the benefit probably still outweighs the risk in short prognosis and acute symptoms. Existing evidence is inconclusive for steroid treatment of COVID-19 patients, and especially those on hospice.

WHO and CDC recommend that corticosteroids not be routinely used in patients with COVID-19 for treatment of viral pneumonia or ARDS unless indicated for another reason (e.g., asthma or COPD exacerbation, septic shock).⁵ However, this does not consider the end-of-life population.

4. ACE inhibitors: continue if clinically appropriate

The American Heart Association, the Heart Failure Society of America, and the American College of Cardiology (ACC) issued a joint statement urging patients with cardiovascular disease diagnosed with COVID-19 to continue taking their ACE inhibitors and ARBs as prescribed.⁶ Evidence does not support discontinuation if infected with COVID-19, and the benefits are expected to outweigh risks. However, for other reasons, such as low blood pressure, dysphagia, or overall decline, ACE inhibitors may not be appropriate to continue in all hospice patients.

5. Off-Label use of medications to prevent or treat COVID-19 infection: AVOID

Examples include hydroxychloroquine, chloroquine, azithromycin, quercitin, and others. No medication is currently FDA approved for COVID-19 prevention or treatment, as their safety and efficacy have not been established in clinical trials. Use of medications for COVID-19 would be off-label, and is not recommended.

The FDA recently issued an emergency use authorization (EUA) for hydroxychloroquine and chloroquine to be used from the Strategic National Stockpile (SNS), for the treatment of certain hospitalized teens and adults with COVID-19 .⁷ EUAs enable new products or new uses for existing drugs without clinical trials, if the benefits appear to outweigh the known risks, and there are no alternatives. This EUA does not support use of hydroxychloroquine or chloroquine outside of those terms (i.e. for prevention, or in non-hospitalized patients). Regardless, most hospice patients do not meet these criteria, and goals of care do not typically align with curative treatment.

In hospice patients, including those with confirmed or suspected COVID-19, continue to carefully evaluate goals of care if considering treatment for COVID-19. We do not recommend any medications for prevention of COVID-19 at this time. We recommend reserving hydroxychloroquine, chloroquine, and other antibiotics for when the patient has an FDA-approved indication for one of these medications. However, due to widespread but unsupported off-label use and hoarding, there are now significant shortages of these medications, impacting those patients with approved indications, such as lupus and rheumatoid arthritis.

Many therapies for management of symptoms related to COVID-19 or other conditions exist. Please contact a ProCare HospiceCare clinical pharmacist at 866-264-7496 for patient-specific recommendations.

Written by: Kristin Speer, Pharm.D. BCPS

References:

Amirav I, Newhouse T. ‘RE: Transmission of Corona Virus by Nebulizer- a serious, underappreciated risk!’ CMAJ. 3 March 2020. URL: https://www.cmaj.ca/content/re-transmission-corona-virus-nebulizer-serious-underappreciated-risk
WHO communication via Twitter, March 18, 2020. https://twitter.com/WHO/status/1240409217997189128
FDA advises patients on use of non-steroidal anti-inflammatory drugs (NSAIDs) for COVID-19. FDA Website. Accessed April 4, 2020. URL: https://www.fda.gov/drugs/drug-safety-and-availability/fda-advises-patients-use-non-steroidal-anti-inflammatory-drugs-nsaids-covid-19
Fang L et al. Are patients with hypertension and diabetes mellitus at increased risk for COVID-19 infection? Lancet Respir Med2020 Mar 11; [e-pub]. ( https://doi.org/10.1016/S2213-2600(20)30116-8 )
Interim Clinical Guidance for Management of Patients with Confirmed Coronavirus Disease (COVID-19). CDC Website. Accessed April 4, 2020. URL: https://www.cdc.gov/coronavirus/2019-ncov/hcp/clinical-guidance-management-patients.html
Patients taking ACE-i and ARBs who contract COVID-19 should continue treatment, unless otherwise advised by their physician: Statement from the American Heart Association, the Heart Failure Society of America and the American College of Cardiology [press release]. 2020 Mar 17. ( https://www.hfsa.org/patients-taking-ace-i-and-arbs-who-contract-covid-19-should-continue-treatment-unless-otherwise-advised-by-their-physician/ )
FDA Emergency Use Authorization For Use of Chloroquine Phosphate or Hydroxychloroquine Sulfate Supplied From the Strategic National Stockpile for Treatment of 2019 Coronavirus Disease. March 28,2020. URL: https://www.fda.gov/media/136534/download

FDA Requests Withdrawal of Ranitidine Medications from Market Due to NDMA

Wed, 08 Apr 2020 22:34:26 GMT

The U.S. Food and Drug Administration (FDA) has identified that some ranitidine products, including those commonly known as the brand name drug, Zantac®, contain a nitrosamine impurity called N-nitrosodimethylamine (NDMA) at low levels. NDMA is classified by U.S. government organizations, such as the Environmental Protection Agency (EPA), as a probable human carcinogen (a substance that could cause cancer).

The FDA has determined that the NDMA impurity in these ranitidine products increases over time, and when stored at higher than room temperatures, may result in consumer exposure to unacceptable levels. As a result, on April 1, 2020, the FDA announced that it is requesting manufacturers withdraw all prescription and over-the-counter (OTC) ranitidine medications from the market immediately.

Important information to keep in mind:

As a result of this market withdrawal request, ranitidine products will not be available for new or existing prescriptions or OTC use in the U.S.
The FDA is recommending that individuals who take OTC ranitidine stop taking it at this time, and that individuals who take prescription ranitidine consult with their healthcare professional about other treatment options before stopping the medicine.
In light of the current COVID-19 pandemic, the FDA recommends patients and consumers not take their medicines to a drug take-back location. Follow the specific disposal instructions in the medication guide or package insert, or follow the FDA’s recommended steps for disposal of unused medications. At this time, ranitidine has NOT been added to the Do Not Flush list.
Ranitidine is a histamine-2 (H2) antagonist used to decrease acid produced in the stomach. Multiple drugs are approved for the same or similar uses that do not carry the same risks from the NDMA impurity. To date, the FDA’s testing has not found NDMA in famotidine (Pepcid®), cimetidine (Tagamet®), esomeprazole (Nexium®), lansoprazole (Prevacid®), or omeprazole (Prilosec®).

ProCare clinical pharmacists are available directly through option #4, 24/7, to assist with decision making for the best therapeutic alternatives for your patients. Additionally, your Account Manager can assist with any formulary changes based on the information above. Thank you for your continued partnership.

Reference:

United States Food & Drug Administration, April 2020.

An Update on the Use of Methadone in Hospice & Palliative Care

Mon, 06 Apr 2020 22:32:28 GMT

Methadone was first developed in Germany in the 1930s and was used extensively during World War II as an alternative to morphine during shortages. Over the past twenty years, methadone has experienced a revival due to its unique characteristics, versatile administration, and utility in managing nociceptive and/or neuropathic pain in hospice and palliative care (Figure 1).

Conversion to Methadone from Another Opioid:

Converting from one oral (PO) opioid to methadone is a complex process, especially if the patient is at a very high dosage. However, a recent expert consensus report by McPherson and team entitled, Safe and Appropriate Use of Methadone in Hospice and Palliative Care, provides a more streamlined approach to dosing conversions (Figure 2). Please note that PO methadone dosing conversions are not linear; this means that the conversion ratio increases as the oral morphine dose (or equivalent amount of other opioid) increases. Compare that to a linear conversion, where the ratio of one opioid to the other will always be the same (e.g. always 1:5 or always 1:10), regardless of the starting dose of the initial opioid. In a non-linear conversion (as with methadone), use of high but ineffective doses of previous opioid(s) may result in overestimation of the equivalent methadone dose, so the initial total methadone dose should generally not exceed 40mg per day. Methadone dosing conversions are also not bi-directional; this means that the same conversion factor used to convert from an opioid to methadone is not used to convert from methadone back to the initial opioid. A consultation with a clinical pharmacist that specializes in pain management or hospice and palliative care is generally recommended when transitioning to or making significant changes to a methadone regimen, and “methadone checks” to monitor the safety and efficacy of the patient’s methadone therapy are generally recommended for the first 5-7 days after starting or making a change to a methadone regimen.

Appropriate Patients for Methadone Use (or Non-Use):

Despite its unique characteristics and advantages, methadone is not appropriate for everyone. With a few exceptions, patients with a prognosis of one week or less generally should not convert completely over to methadone since it may take seven or more days to reach steady state and achieve long-acting effects. If a patient lives alone and is unreliable/noncompliant, then methadone is generally not recommended. Likewise, if a patient has poor cognitive function and does not have a reliable caregiver, then methadone is generally not recommended either. The following patient populations are at increased risk of adverse outcomes or toxicity, but may still be considered for methadone therapy, if appropriate: those with significant cardiac disease (especially in the presence of hypokalemia, a pacemaker or other risks for QTc prolongation), severe liver disease, obstructive or central sleep apnea, multiple risk factors for toxicity (e.g. clinical instability, multiple transitions in care, history of transplant, etc.), multiple interacting medications, and/or a history of substance misuse/abuse. Ultimately, each patient should be assessed on a case-by-case basis prior to starting methadone to ensure that the benefits outweigh the risks.

Written by: Brett Gillis, Pharm.D.

References:

Chary S, Palat G. Practical guide for using methadone in pain and palliative care practice. Ind J Pal Care 2018; 24(1):21-29.
Hamid K. Pain management: the use of methadone in hospice and palliative care. ProCare 2018.
McPherson ML, Walker KA, Davis MP et al. Safe and appropriate use of methadone in hospice and palliative care: expert consensus white paper. J Pain Sympt Mgt 2019; 57:635-647.
Methadone monograph. CESAR Center for Substance Abuse: University of Maryland 2016.
Speer K. Safe and effective methadone use in hospice patients. ProCare 2019.

Cannabinoids Found Ineffective for Cancer Pain

Tue, 03 Mar 2020 23:29:18 GMT

Last month, a meta-analysis¹ of 1,442 patients and 5 randomized controlled trials found cannabinoids did not reduce cancer pain any better than placebo, when these were added to stable doses of opioids. Change in pain score using the numeric rating scale (NRS) was the primary outcome. The analysis also found statistically significant increased frequencies of somnolence and dizziness as compared with placebo. The cannabinoids were administered in a pump oromucosal spray formulation (not currently available in the US), using equal parts CBD (cannabidiol) and THC (tetrahydrocannabidiol) mixture.

This study drew the same conclusions as a 2019 systematic review.²

The authors of the meta-analysis used a detailed search strategy and included studies considered to be low risk of bias. However, it should be noted that it is possible not all relevant studies were included, and there were inconsistencies between studies about the patients included, the interventions, comparators, and outcomes. Aside from lack of CBD efficacy, negative results from some of the included trials could have been due to high withdrawal rates from studies and/or high mortality rates, among other factors.

The authors conclude that cannabinoids cannot be recommended for the treatment of cancer-related pain. However, this conclusion may not apply to all cannabinoid products, as they all have not been studied in this setting. Additionally, non-physical pain factors, which were not evaluated, can play an important role in a patient’s total pain. For example, subgroups of patients with significant anxiety or depression may have shown a benefit but were not stratified out in the analysis. It is also important to recognize that, despite these results, many patients do individually report beneficial outcomes, and their experiences should be respected. In patients who are using cannabinoids to help reduce cancer-related pain, it may be a reasonable approach to allow its continued use as long as there are no apparent significant negative effects.

By Kristin Speer, Pharm.D., BCPS

References:

Boland EG, Bennett MI, Allgar V, et al. Cannabinoids for adult cancer-related pain: systematic review and meta-analysis. BMJ Supportive & Palliative Care Published Online First: 20 January 2020. doi: 10.1136/bmjspcare-2019-002032
Häuser, W., Welsch, P., Klose, P. et al. Schmerz. Efficacy, tolerability and safety of cannabis-based medicines for cancer pain. (2019) 33: 424. https://doi.org/10.1007/s00482-019-0373-3

Psychiatric Medication-Related Issues in Hospice

Thu, 16 Jan 2020 23:25:04 GMT

Medications used to treat psychiatric conditions and symptoms are commonly used in the hospice setting. It has been reported that antipsychotics are in the top 20 most frequently prescribed pharmacological class of medications in hospice patients. Adverse effects of these medications can easily be overlooked but can have significant effects on the patient. This article will examine adverse events associated with common psychiatric medications, including serotonin syndrome, neuroleptic malignant syndrome, extrapyramidal symptoms, and tardive dyskinesia.

Serotonin Syndrome

With a substantial increase in antidepressant use in the United States over the last two decades, serotonin syndrome (SS) has become an increasingly common and significant clinical concern. Serotonin syndrome can be described as a progression of serotonergic toxicity based on increasing concentration levels of serotonin affecting the central and peripheral nervous systems. The classic presentation of SS is the triad of autonomic dysfunction, neuromuscular excitation, and altered mental status. Symptoms can range from tremor, twitching, and diaphoresis in mild serotonin toxicity, to severe myoclonus, seizures and multi-organ failure in severe toxicity.

Serotonin Syndrome. Retrieved from https://www.mycpdzw.org/common-emergencies-detail/50 .

Medications most commonly associated with SS are classified according to mechanism in the following table.

The two mainstays of serotonin syndrome management are to discontinue the serotonergic agent and to give supportive care. Symptomatic treatment with a benzodiazepine, such as lorazepam or diazepam, is often used to treat agitation and clonus. Serotonin antagonists have had some success in case reports. Cyproheptadine and chlorpromazine have been used, but require further investigation beyond individual case reports to determine their effectiveness and reliability in treating serotonin syndrome.

Neuroleptic Malignant Syndrome

Neuroleptic malignant syndrome (NMS) is a life-threatening idiosyncratic reaction to any medication that blocks dopamine, most commonly the antipsychotic drugs, but it can also happen with the rapid withdrawal of dopaminergic medications. The clinical course typically begins with muscle rigidity, also referred to as “lead-pipe” rigidity, followed by a fever within several hours of onset and mental status changes that can range from mild drowsiness, agitation, or confusion, to severe delirium or coma. See the following table of NMS symptoms.

The primary trigger of NMS is dopamine receptor blockade and the standard causative agent is an antipsychotic. Potent typical antipsychotics such as haloperidol or chlorpromazine have been most frequently associated with NMS and thought to have the greatest risk (see table at bottom for typical and atypical antipsychotics). Although atypical antipsychotics appear to have a reduced risk of developing NMS compared to typical antipsychotics, a significant number of cases have been reported with some atypical antipsychotics including risperidone and olanzapine. NMS has also been associated with non-neuroleptic agents that have antidopaminergic activity such as metoclopramide. Another cause of NMS is the abrupt cessation or reduction in dose of dopaminergic medications such as levodopa in Parkinson’s disease.

When treating NMS, typically the first step in essentially all cases is discontinuing the causative neuroleptic medication (however, if the syndrome has occurred in the setting of an abrupt withdrawal of a dopaminergic medication, then this medication is reinstituted as quickly as possible). The next step is to give supportive therapy. The two most frequently used medications are bromocriptine mesylate, a dopamine agonist, and dantrolene sodium, a muscle relaxant. Anecdotal reports have shown these agents may shorten the course of the syndrome and possibly reduce mortality when used alone or in combination. Additional pharmacologic agents that may have some utility in treating NMS include benzodiazepines, which can be helpful in controlling anxiety and agitation.

Extrapyramidal Symptoms

A variety of movement disorders have been described along the spectrum of extrapyramidal symptoms (EPS), including dystonia, akathisia, and parkinsonism. These symptoms are very debilitating for the patient, interfering with social functioning and communication, motor tasks, and activities of daily living. Dystonia most often occurs within 2-5 days of drug exposure and manifests with involuntary muscle contractions resulting in abnormal posturing or repetitive movements. Akathisia is characterized by a subjective feeling of internal restlessness and a compelling urge to move, leading to repetitive movements comprising leg crossing, swinging, or shifting from one foot to another. Drug-induced parkinsonism presents as tremor, rigidity, and slowing of motor function, or bradykinesia.

The medications most commonly associated with EPS are the centrally-acting, dopamine-receptor blocking agents, namely the first-generation (typical) antipsychotics, such as haloperidol. While EPS occurs less frequently with atypical antipsychotics, the risk increases with dose escalation. Other agents that block central dopaminergic receptors have also been identified as causative of EPS, including metoclopramide and prochlorperazine.

Managing EPS typically involves discontinuing the offending medication, or even switching to an atypical antipsychotic. Antimuscarinic medications, such as diphenhydramine, benztropine, or trihexyphenidyl, are also used to treat these symptoms. Akathisia can also be managed by use of the beta-blocker, propranolol, and parkinsonism symptoms can be treated with use of anti-Parkinson agents, such as levodopa or amantadine.

Tardive Dyskinesia

Tardive dyskinesia (TD) is a movement disorder that causes involuntary, repetitive body movements of the face, lips, tongue, trunk and extremities. It is most commonly seen in patients who are on long-term treatment with antipsychotic medications. The most common symptoms are orofacial dyskinesia and dyskinesia of the limbs. In many patients, TD is irreversible and can persist long after the causative medications are stopped.

Typical antipsychotics are the most likely to cause TD, while atypical antipsychotics seem to be associated with a decreased prevalence. Antidepressants, such as SSRIs and MAOIs are also associated with TD, but appear to have less risk than antipsychotics. Other medications that block dopamine, including metoclopramide and prochlorperazine, can also cause TD.

Management of TD involves discontinuing the offending agent. The FDA has approved a new class of medications called the vesicular monoamine transporter 2 (VMAT2) inhibitors, which are indicated for the treatment of TD in adults.

Examples of Typical and Atypical Antipsychotics

Among our hospice patients, use of these medications to treat various conditions at end-of-life is very prevalent. Symptoms of these adverse events can easily be overlooked or misattributed to be ‘part of the dying process’. Thus, knowledge of these adverse events is critical when evaluating patient symptoms while taking these medications, to prevent further morbidity. When in doubt, a ProCare clinical pharmacist, available 24/7/365, can help assess the possibility of an adverse event from a psychiatric medication, and can assist in its management.

Written by: Kiran Hamid, R.Ph.

References

Wang, R. et al. (2016, November). Serotonin syndrome: Preventing, recognizing, and treating it. Retrieved from https://www.mdedge.com/ccjm/article/120386/neurology/serotonin-syndrome-preventing-recognizing-and-treating-it/page/0/1
Boyer, E. (2018, March 12). Serotonin syndrome (serotonin toxicity). Retrieved from https://www.uptodate.com/contents/serotonin-syndrome-serotonin-toxicity
Berman, B. (2011, January). Neuroleptic Malignant Syndrome: A Review for Neurohospitalists. Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3726098/
Wijdicks, E. (2019, May 31). Neuroleptic Malignant Syndrome. Retrieved from https://www.uptodate.com/contents/neuroleptic-malignant-syndrome
D’Souza, R. Hooten, W. M. (2019, January 9). Extrapyramidal Symptoms (EPS). Retrieved from https://www.ncbi.nlm.nih.gov/books/NBK534115/ .
Jackson, N. et al. (2008, March) Neuropsychiatric complications of commonly used palliative care drugs. Retrieved from https://pmj.bmj.com/content/84/989/121.full
Cornett, E. et al. (2017, July). Medication-Induced Tardive Dyskinesia: A Review and Update. Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5472076/
Muench, J. Hamer, A. (2010, March 1). Adverse Effects of Antipsychotic Medications. Retrieved from https://www.aafp.org/afp/2010/0301/p617.html .
Ferguson, J. (2001, February). SSRI Antidepressant Medications: Adverse Effects and Tolerability. Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC181155/
Serotonin Syndrome. Accessed 9/25/19. Retrieved from https://www.mycpdzw.org/common-emergencies-detail/50 .
Neuroleptic Malignant Syndrome. Accessed 9/25/19. Retrieved from http://klossandbruce.com/video-flashcard-neuroleptic-malignant-syndrome

A Review of Benzodiazepines

Tue, 10 Dec 2019 23:15:09 GMT

Benzodiazepines are used for a variety of indications in the hospice setting, including insomnia, breathlessness, agitation, seizures, nausea/vomiting, myoclonus, and palliative sedation (see details outlined below).

Although they share many class effects, unique properties of individual benzodiazepines have clinical implications. For example, benzodiazepines can be classified based on their half-life (short, intermediate, and long). The benzodiazepine with the shortest half-life is triazolam. The longest is diazepam. The terminal half-life may be affected by liver or kidney dysfunction, age, drug-drug interactions, gender, race, or even route of administration. For example, the half-life of diazepam may be up to 174 hours when administered intramuscularly.

The side effect profile of benzodiazepines is similar, varying slightly among different agents. Some of the most common include: CNS depressant effects (altered mental status, anterograde amnesia, paradoxical reactions), gastrointestinal (constipation, appetite changes), genitourinary (urinary retention), cardiovascular (hypotension), and ophthalmic (visual disturbance).

Older adults have increased sensitivity to benzodiazepines and decreased metabolism of long-acting agents, and thus adverse effects may be more pronounced. The American Geriatrics Society (AGS) Beers Criteria recommends the use of short-acting benzodiazepines in appropriate circumstances. Short-acting agents (classified by AGS) are alprazolam, estazolam, lorazepam, oxazepam, temazepam, and triazolam. The “L.O.T.” benzodiazepines are l orazepam, o xazepam, and t emazepam. They are metabolized by direct, rapid conjugation in the liver, a process that is not altered in the setting of liver disease, so they do not produce active metabolites. Thus, “L.O.T” benzodiazepines may be considered lower risk than others for accumulation and related side effects.

Insomnia

It is recommended to use a short-acting benzodiazepine for patients with difficulty falling asleep, such as triazolam.
For patients with trouble maintaining sleep, consider a benzodiazepine with a longer half-life, such as temazepam.

Breathlessness

Benzodiazepines actually have no effect on respiration at normal doses.
Slight depression of ventilation at higher doses
Relief comes from anxiolytic effects (reserve for breathlessness caused by anxiety/fear).
Consider as 2nd or 3rd line agent after opioids and non-pharmacological treatment options.

Agitation

They only have sedative effects when used alone in a patient with psychosis (do not have anti-psychotic properties by themselves).

Seizures

First-line agents include, midazolam IM, lorazepam IV, or diazepam IV.
In the home setting, or where parenteral therapy is not feasible, consider lorazepam PO/SL/PR, diazepam PO/SL/PR, or midazolam intranasally.
For seizure maintenance therapy, lorazepam, diazepam, or clonazepam may be given routinely.

Myoclonus

Benzodiazepines can be considered for treatment of opioid-induced myoclonus.
Diazepam, clonazepam, or lorazepam are typically used.

Nausea/Vomiting

Proven effective as an adjunct for chemotherapy induced nausea/ vomiting (CINV) and anticipatory nausea/ vomiting (ANV).
Relief mainly comes from anxiolytic effects (reserve for nausea /vomiting caused by anxiety/fear).
Lorazepam is most commonly used.

Palliative Sedation

Midazolam rapidly penetrates the CNS and can be given as an IV or sub-cut infusion.
Use of midazolam in this setting should be done in close consult with or by an experienced palliative care provider.

Other Uses for Benzodiazepines at End-of-Life

Hiccups
Restless leg syndrome
Essential tremor

Benzodiazepines are useful in the management of various symptoms encountered in hospice and palliative care. Knowledge of the pharmacology of these medications will aid in choosing the most effective and safest agent.

Written by: Shaun Gutstein, Pharm.D.

Reference

American Geriatrics Society 2015 Beers Criteria Update Expert Panel. American Geriatrics Society 2015 Updated Beers Criteria for Potentially Inappropriate Medication Use in Older Adults. J Am Geriatr Soc. 2015; 63(11): 2227-46.
Benzodiazepine Comparison Table. Lexi-Drugs. Lexicomp. Wolters Kluwer Health, Inc. New York, NY. Available at: http://online.lexi.com. Accessed June 22, 2019.
Berger MJ, Ettinger DS, Aston J, et. al. NCCN Guidelines Insights: Antiemesis, Version 2.2017. J Natl Compr Canc Netw. 2017; 15(7): 883-893.
Buysse DJ. Insomnia. JAMA. 2013; 309(7): 706-16.
Carlos K, Prado GF, Teixeira CD, et. al. Benzodiazepines for restless legs syndrome. Cochrane Database Syst Rev. 2017; 3: CD00693
Caviness JN. Treatment of Myoclonus. Neurotherapeutics. 2014; 11(1): 188–200.
Cherny NI, ESMO Guidelines Working Group. ESMO Clinical Practice Guidelines for the management of refractory symptoms at the end of life and the use of palliative sedation. Ann Oncol. 2014; 25 Suppl 3: iii143-52.
Glauser T, Shinnar S, Gloss D, et. al. Evidence-Based Guideline: Treatment of Convulsive Status Epilepticus in Children and Adults: Report of the Guideline Committee of the American Epilepsy Society. Epilepsy Curr. 2016; 16(1): 48-61.
Hui D, Frisbee-Hume S, Wilson A. et. al. Effect of Lorazepam With Haloperidol vs Haloperidol Alone on Agitated Delirium in Patients With Advanced Cancer Receiving Palliative Care: A Randomized Clinical Trial. JAMA. 2017; 318(11): 1047-1056.
Jeon YS, Kearney AM, Baker PG. Management of hiccups in palliative care patients. BMJ Support Palliat Care. 2018; 8(1)
Maltoni M, Scarpi E, Rosati M, et. al. Palliative sedation in end-of-life care and survival: a systematic review. J Clin Oncol. 2012; 30(12): 1378-83.
Simon ST, Higginson IJ, Booth S, et. al. Benzodiazepines for the relief of breathlessness in advanced malignant and non-malignant diseases in adults. Cochrane Database Syst Rev. 2016; 10:CD007354.
Wick J. The History of Benzodiazepines. Consult Pharm. 2013; 28(9): 538-48.
Wilson MP, Pepper D, Currier GW, et. al. The psychopharmacology of agitation: consensus statement of the American association for emergency psychiatry project Beta psychopharmacology workgroup. West J Emerg Med. 2012; 13(1): 26-34.
Zesiewicz TA, Elble R, Louis ED, et. al. Practice parameter: therapies for essential tremor: report of the Quality Standards Subcommittee of the American Academy of Neurology. Neurology. 2005; 64(12): 2008-20.

Case Study

Tue, 19 Nov 2019 23:11:37 GMT

History:

The patient was on a high dose morphine, patient-controlled analgesia (PCA) pump and had severe cancer pain. He reported to have "pain all over" even when not being touched. He developed a myoclonic twitch several days prior. He wanted to die early and was suicidal due to the pain and discomfort. Goals of care were to manage his pain with oral medications so he could be more mobile and spend time with family. But since his pain could not be controlled with IV morphine via PCA pump, the team was hesitant to remove or reduce the pump for fear of increasing his pain. They were stuck, and so was the patient.

As a result, ProCare PharmacyCare clinical pharmacy was consulted.

Intervention:

Upon review of the case, the patient seemed to be suffering from opioid (morphine) toxicity: "pain all over" suggested allodynia and hyperalgesia, and myoclonic twitching is another sign/symptom of morphine neurotoxicity. The pharmacy determined the patient was a good candidate for oral methadone, which can help reduce opioid toxicity and tolerance. A 5-day cross-taper was constructed off the morphine PCA and onto oral methadone.

Results :

The patient was successfully transferred onto oral methadone and off the PCA and needed methadone 45mg/day in divided doses to control his pain. Hyperalgia, allodynia, and twitching resolved. He also rallied: he lived longer than expected. He was found playing cards with his daughter one night. He was able to attend a grandson's basketball game, another grandson's concert recital, and dine out with family. He died happily and in minimal to no pain.

Opioids and Pain Management: Allergies, Conversions, Dysphagia, Oh My!

Thu, 07 Nov 2019 17:04:46 GMT

Pain is one of the most common symptoms we encounter as hospice clinicians, but it is also the most difficult to treat, particularly with opioid allergies, complex opioid conversions, and declining ability to swallow.

Opioid Allergies

There are three different allergy subtypes, ranging from common adverse effects to true allergies, which are rare occurrences. Adverse effects are the most common and are defined as predictable effects based on the medication’s mechanism of action (e.g. nausea/vomiting, constipation, or drowsiness). Pseudo-allergies are unpredictable hypersensitivity reactions that occur after the first dose of an opioid and can range from itching to hives. True allergies are immune-mediated hypersensitivity reactions that occur after prior exposure or repeat dosing. Examples of severe true allergic reactions include: angioedema (swelling of the face, lips, and tongue), maculopapular rash, hypotension, and shock. Be sure to document the reaction type whenever possible for a complete allergy record and to ensure the safety of your patients upon switching to another opioid. There are five different chemical classes of opioids, and each class has a distinct chemical structure (Table 1). What this means is that even with a true allergy to one class of opioids, there should still be several options in another class to treat the patient’s pain.

Table 1 depicts the parent opioid in each class with its derivatives. If a patient has an allergic reaction to the parent drug, it’s likely that they may have that exact same reaction to a derivative.

*Decreased cross-tolerability within class

Conversions

It’s important to keep in mind that there isn’t a set formula for opioid conversions that works every time. Each calculation should be based on the individual patient, the amount of medications they are taking, pertinent history, and their goals for pain management. Consider following the steps below for a straightforward opioid conversion:

Step One: Convert all daily opioid usage from scheduled and PRN orders over to Oral Morphine Equivalents (OME).

Step Two: Use your hospice’s approved opioid conversion chart to convert between opioids.

(Example: Morphine to Hydromorphone; Tramadol to Oxycodone IR).

Please note that conversion to Fentanyl patches or Methadone requires use of medication-specific conversion charts.

Step Three: Reduce the final number by 25-33% to account for incomplete cross-tolerance.

Step Four: Double check your calculations, and when in doubt, call your friendly PHC pharmacist for help. Depending on the patient’s pain level and available dosage forms, you may round up or down.

Dysphagia

As patients approach end-of-life, up to 70% of patients require a non-oral route (NPO) for opioid administration. The non-oral routes that have the most supporting data are intravenous, subcutaneous, transdermal patches, and the enteral route. Routes with mixed supporting data are sublingual, buccal, rectal, and topical administration. Sublingual and rectal routes are used frequently in our patient population for convenience; however, absorption can be highly variable, depending on the medication used. The routes with the least supporting data are intramuscular injections, intravaginal, and intranasal.

Table 2 lists the various non-oral routes of administration, with examples of opioids that can be given via the route and the onset of action.

Pain management is complicated for our hospice and palliative care patients. As hospice clinicians, it’s imperative to ensure we anticipate a patient’s pain, double check conversion calculations, understand the nuances of opioid allergies, and pick the proper route of administration for maximum efficacy. This is truly the recipe for success, comfortable patients, and happy caregivers.

Written by: Meri Madison, Pharm.D.

References:

Fudin J. Opioid Allergy, Pseudo-allergy, or Adverse Effect? US Pharm. 2018;3. Available Online from : https://www.pharmacytimes.com/contributor/jeffrey-fudin/2018/03/opioid-allergy-pseudo-allergy-or-adverse-effect.
Fudin J. Chemical Classes of Opioids. Pain Dr. http://paindr.com/wp-content/uploads/2018/02/Opioid-Structural-Classes-Figure_-updated-2018-02.pdf. Updated February 8, 2018.
Gagnon B, Almahrezi A, Schreier G. Methadone in the treatment of neuropathic pain. Pain Res Manag. 2003;8:149-154.
Manfredi PL, Houde RW. Prescribing methadone, a unique analgesic. J Support Oncol. 2003 Sep-Oct;1(3):216-20.
Morley JS, Bridson J, Nash TP, et al. Low-dose methadone has an analgesic effect in neuropathic pain: a double-blind randomized controlled crossover trial. Palliat Med. 2003;17:576-587.
Mercadante S, Casuccio A, Fulfaro F, Groff L, Boffi R, Villari P, Gebbia V, Ripamonti C. Switching from morphine to methadone to improve analgesia and tolerability in cancer patients: a prospective study. J Clin Oncol. 2001 Jun 1;19(11):2898-904.
Kestenbaum MG. et al. Alternative Routes to Oral Opioid Administration in Palliative Care: A Review and Clinical Summary. Pain Medicine 2014; 15: 1129–1153.
Narang N and Sharma AJ. Sublingual mucosa as a route for systemic drug delivery. International Journal of Pharmacy and Pharmaceutical Sciences 2011. 3(Supply2); 15-22.
Chang A et al. Transmucosal Immediate-Release Fentanyl for Breakthrough Cancer Pain: Opportunities and Challenges for Use in Palliative Care, Journal of Pain & Palliative Care Pharmacotherapy, 2015. 29:3, 247-260.
Latuga NM et al. (2018) A Cost and Quality Analysis of Utilizing a Rectal Catheter for Medication Administration in End-of-Life Symptom Management, Journal of Pain & Palliative Care Pharmacotherapy, 32:2-3, 63-70.

Why Anticoagulants are Stopped in Hospice

Mon, 14 Oct 2019 15:56:28 GMT

Hospice goals of care focus on optimizing comfort and quality of life, rather than treatment and prevention. Anticoagulation therapy and monitoring are not aligned with comfort and quality of life, and can cause harm from bleeding. Anticoagulation does not provide comfort or control symptoms. For these reasons, anticoagulation is frequently discontinued.

There is a single, serious reason why anticoagulants are commonly discontinued in hospice: potentially serious (or sometimes deadly) bleeding.

However, taking an anticoagulant does not mean you are going to bleed. Taking an anticoagulant increases your bleed risk. And other factors can additionally increase your risk of bleeding while taking an anticoagulant. The more bleeding risk factors a patient has, the more reasons why an anticoagulant should be stopped. Typically, hospice patients have many risk factors for bleeding.

Here is an overview of risk factors for bleeding aside from taking an anticoagulant (not all-inclusive):

Another reason anticoagulants are stopped is because the patient no longer has any reason to be taking one. For example, for stroke prevention in patients with atrial fibrillation, patients without symptoms under the age of 65 and no other stroke risk factors should not be taking anticoagulants. Also, anticoagulants should be stopped after 3-6 months if a clot in the leg (deep vein thrombosis) or lung (pulmonary embolus) was a first event and caused by a temporary risk factor such as trauma, surgery, or use of hormonal contraception. Sometimes anticoagulants are unintentionally continued when they should have been stopped.

Finally, one of the oldest and most common anticoagulants, warfarin, requires INR monitoring and a consistent diet, which can be cumbersome, and potentially causes more anxiety in end-of-life due to the need to keep INR levels within range.

A quick note about aspirin – this is an antiplatelet, which has a different mechanism from anticoagulants, but nonetheless increases bleed risk, also. Many of the same concepts above also apply to aspirin. Aspirin, however, does not require INR monitoring and does not participate in as many drug interactions. There is no reversal agent, but its duration of action is generally shorter than anticoagulants. For these reasons, aspirin may be a more attractive alternative. Unfortunately, aspirin is not very effective for preventing or treating all of the same events as anticoagulants. Thus, if aspirin is used to replace anticoagulants, it may simply increase bleed risk and pill burden without any meaningful reduction of the risk of clotting events. Generally, aspirin is recommended to be discontinued in hospice.

It is best to discuss your concerns about stopping clot-prevention therapy with your hospice team. They can help answer any questions you might have, and help weigh the risks and benefits of continuation or discontinuation. Ultimately, they can help you feel more comfortable about your decision either way.

References:

Li L, Geraghty OC, Mehta Z, Rothwell PM. Oxford Vascular Study. Age-specific risks, severity, time course, and outcome of bleeding on long-term antiplatelet treatment after vascular events: a population-based cohort study. Lancet. 2017;390(10093):490-499.
Lip GYH, et al. Antithrombotic therapy for atrial fibrillation. CHEST. 2018;154(5):1121 – 1201.
Kearon C, Akl EA, Comerota AJ, Prandoni P, Bounameaux H, Goldhaber SZ, et al. Antithrombotic therapy for VTE disease: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. CHEST. 2012;141(2 Suppl):e419S.

The Management of Insomnia in Hospice Care

Tue, 10 Sep 2019 15:30:41 GMT

Insomnia is defined as difficulty falling asleep, difficulty staying asleep, and/or having non-restorative sleep, and it is most often secondary to another cause or condition. Common causes of insomnia that can be especially common in the hospice population include the following: situational (e.g. interpersonal conflict/family dynamic issues); medical (e.g. cardiac, respiratory, pain, diabetes, GERD, epilepsy, Parkinson’s disease); psychiatric (e.g. depression, anxiety); and pharmacologic (e.g. beta-blockers, diuretics, steroids, SSRI antidepressants). Whenever possible and as appropriate, it is recommended to treat and resolve the cause(s) of insomnia first, before adding a medication to treat the symptom of insomnia.

Non-pharmacologic measures should be used whenever possible to manage insomnia. In the hospice population, these might include:

Medication Therapies for Insomnia

There are a number of different types of medications that are used to treat insomnia:

Benzodiazepines

Temazepam (Restoril®) is FDA-approved for the treatment of insomnia, while lorazepam (Ativan®) is sometimes used off-label for the treatment of insomnia (typically for insomnia due to anxiety). Lorazepam and temazepam are among the benzodiazepines considered less risky for use in elderly patients.

Nonbenzodiazepine GABAA Agonists

These medications are also known as the “Z” drugs: zolpidem (Ambien®), zaleplon (Sonata®), eszopiclone (Lunesta®). The FDA recently added a Black Box Warning for these medications, because they have been associated with complex sleep behaviors that have resulted in serious injuries and death. These behaviors can occur after the first dose or after longer periods of use, even at the lowest recommended doses. The FDA also added a contraindication against use of these drugs in patients who have experienced an episode of complex sleep behavior in the past with their use. Due to safety, the max dose in the elderly and in female patients is 5mg per night.

Melatonin Receptor Agonist: ramelteon (Rozerem®)

Ramelteon works by binding to and stimulating the melatonin receptors in the central nervous system (CNS). Although this medication is reported to have minimal adverse effects and no withdrawal or rebound insomnia effects as compared to placebo, it is considered non-preferred in hospice due to its relatively high cost.

Orexin Antagonist: suvorexant (Belsomra®)

Suvorexant blocks the neuropeptides orexin A and B, which promote wakefulness. It also has minimal adverse effects and no withdrawal or rebound insomnia effects noted when discontinued, but it also tends to be relatively high cost and is therefore non-preferred in hospice.

Antidepressants

These medications are typically (and likely most appropriately) used when the patient also has depression, or when other options have failed. Antidepressants can be sedating due to a variety of mechanisms, but they tend to lack data regarding their use in primary insomnia (with the exception of doxepin). The following antidepressants have support for off-label use for insomnia:

Antipsychotics

Antipsychotics are not recommended for insomnia alone, but they can be effective for patients with insomnia AND behaviors/symptoms of psychosis, major depressive disorder, or an organic brain syndrome. Of the antipsychotics that are most commonly used in hospice, chlorpromazine (Thorazine®), olanzapine (Zyprexa®), and quetiapine (Seroquel®) tend to be the most sedating. Quetiapine is probably the most cost-effective.

Other Prescription Drugs: gabapentin (Neurontin®)

Typically, gabapentin should not be used for its sleep effects alone, although drowsiness is a somewhat common adverse effect. It may be helpful for patients with insomnia AND restless leg syndrome (RLS) or neuropathic pain.

Over-The-Counter (OTC) Sleep Aids

Antihistamines (e.g. diphenhydramine (Benadryl®), doxylamine) can have significant anticholinergic side effects, especially in elderly patients. Limited evidence exists on the safety and efficacy of use for insomnia. Note that tolerance to their sedative/sleep effects can develop with regular use.

Melatonin supplements mimic the function of the melatonin that our bodies produce, which is beneficial, as melatonin production and peak levels tend to decrease as we age. It is recommended to use the lowest possible dose (1-2mg in elderly patients, 3-5mg in non-elderly), as higher doses can cause supraphysiologic levels which can lead to desensitization. Controlled-release forms should be avoided in the elderly.

As a reminder, ProCare clinical pharmacists are available 24/7 to determine which sleep medications might be the most cost-effective and safe for your patients.

Written by: Joelle Potts, PharmD, BCG

References:

Dopp JM, Phillips BG. Sleep-Wake Disorders. Chapter in: Pharmacotherapy: A Pathophysiologic Approach, 10th Edition; DiPiro JT, et al, Eds. McGraw-Hill Education, New York. 2017. 1111-22.
Winter WC. The Sleep Solution: Why Your Sleep is Broken and How to Fix it. Berkley, Penguin Random House LLC, New York. 2017.
Patel D, Steinberg J, Patel P. Insomnia in the elderly: A review. Journal of Clinical Sleep Medicine; June 15, 2018; 14(6): 1017-24.
Schroeck JL, et al. Review of safety and efficacy of sleep medications in older adults. Clinical Therapeutics. Nov 2016; 38(11): 2340-2372.
Kryger M, Kryger E. What every pharmacist should know about sleep. ASCP Webinars; UAN: 0203-0000-18-076-H01-P. November 3, 2018.
PL Detail-Document, Comparison of Insomnia Treatments. Pharmacist’s Letter/Prescriber’s Letter. July 2014. Last modified January 2015.
Drug monographs. Lexicomp Online, Hudson, Ohio: Wolters Kluwer Clinical Drug Information, Inc., © 2019; last accessed 6/25/2019.
Brooks, Megan. FDA Adds Boxed Warning to Insomnia Drugs. Medscape. April 30, 2019.
2019 American Geriatrics Society Beers Criteria® Update Expert Panel. American Geriatrics Society 2019 Updated AGS Beers Criteria® for potentially inappropriate medication use in older adults. J Am Geriatr Soc 00:1-21, 2019. Available at: [LINK] [last accessed 5/18/2019]
Davis L. Melatonin: Shining some light on the hormone of darkness. ASCP Webinars; UAN: 0203-0000-18-022-H01-P. May 23, 2018.
Natural Products Database, via Lexicomp Online, Hudson, Ohio: Wolters Kluwer Clinical Drug Information, Inc., © 2019; last updated 4/19/2019. [accessed 5/15/2019]

Use of Ketamine for Pain Management in Hospice Care

Fri, 30 Aug 2019 20:54:16 GMT

Ketamine shows promise as an effective option for hospice patients who have pain that does not fully respond to increasing doses of opioids. However, in all instances, this treatment option should be discussed and approved by the patient’s medical provider. It may be especially useful for neuropathic pain that does not respond fully to usual pain regimens that may include, opioids, NSAIDS, certain antidepressants, anticonvulsants, and gabapentinoids. Ketamine appears to be synergistic with opioids in patients who no longer have an analgesic response to high doses of opioids. It is also reported to be opioid-sparing and appears to play a role in opioid potentiation. Keep in mind the use of ketamine for pain is off-label and it can be very complex to dose, so coordination with the patient’s medical provide is critical.

Contraindications, side effects, and monitoring parameters are listed in Table 1. If needed, a ProCare pharmacist can provide information to facilitate your decision about whether or not ketamine would be appropriate.

*Relative contraindications (may not apply to hospice patients). Evaluate risks vs. benefits of using in a hospice patient.

**Less likely with oral administration of ketamine than with infusions.

*** Ketamine does not suppress respiration, but can cause a reversal of opioid tolerance and opioid potentiation, which may suppress respiration if the opioid dose has not been reduced appropriately.

Ketamine is soluble in water and lipids and has many routes of administration. It can be given intravenous, subcutaneous, intramuscular, oral, sublingual, nasal, rectal, topical, and epidural. Dosing via the oral, sublingual, intravenous, and subcutaneous routes are most commonly used for pain and will be reviewed further.

Ketamine dosing is complex. Concurrent opioid adjustments are generally also needed. Oral or sublingual administration of ketamine is preferred. Ketamine infusions can be used, but are best reserved in an inpatient setting, and should not exceed a specified max, in order to avoid anesthesia. See table 2.

When able, patients on continuous infusions of ketamine can be converted to oral ketamine. The conversion range is 1-3:1 IV:PO. If the patient has only been on the ketamine infusion for a few days, use a conversion range of 1:1. Give the total daily oral dose in three divided doses. Generally, a taper off infusion while starting oral medication is recommended. For the first 24 hours, continue parenteral ketamine at 50% or original rate. If possible, reduce parenteral ketamine to 25% of original rate on day 2 before stopping the infusion. Titrate the oral dose by 10-25 mg/day every 3-4 days or by 20-30% every 3-4 days. If the patient experiences pain before next dose is due, consider shortening the dosing interval.

In summary, the advantages, disadvantages, and possible contraindications must be evaluated to determine if the patient is a candidate for ketamine. Some advantages of ketamine include that it is a non-opioid for pain, has no significant effect on pulmonary function, has many routes of administration and is cost-effective when compared to most other pain regimens. Disadvantages may include possible psychotomimetic effects (though not as likely with oral dosing), little data regarding long-term use, it must be compounded for oral or sublingual use, kept refrigerated, and is only good for seven days. Although not a first-line agent for pain, ketamine may provide another good option for patients that fail to fully respond to increasing opioid doses and other adjuvants for pain management, provided the patient’s physician confirms the alternate treatment protocol.

Written by: Karen Bruestle-Wallace, Pharm D, BCGP

References:

Li, L. and Vlidides, P. (2016). Ketamine: 50 Years of Modulating the Mind. Frontiers in Human Neuroscience, 10(612), DOI: 10.3389/fnhum.2016.00612
Ketamine. (2019, March 1). Retrieved from http://www.cesar.umd.edu/cesar/drugs/ketamine.asp
Anderson, L. (2018, Nov. 5). Ketamine Abuse. Retrieved from https://www.drugs.com/illicit/ketamine.html
Lexi-Comp OnlineTM, Lexi-Drugs Online TM, Hudson, Ohio: Lexi-Comp, Inc.; Accessed: June 2018
Ingraham, P. (2018, Nov 21). The 3 Basic Types of Pain Nociceptive, neuropathic and “other” (and then some more”. Retrieved from https://www.painscience.com/articles/pain-types.php
ProCare HospiceCare, (2016). Ketamine Use-Quick Guide. (brochure). Gainesville, GA: ProCare HospiceCare.
Clark, J. (1995). Effective Treatment of Severe Cancer Pain of the Head Using Low-Dose Ketamine in an Opioid-Tolerant Patient. Journal of Pain and Symptom Management, 10(4), 310-314.
Rigo, F. K., Trevisan, G., Godoy, M., Rossato, M., Dalmolin, G., Silva, M.,…Ferreira, J. (2017). Management of Neuropathic Chronic

Diabetes Management at the End-of-Life

Tue, 20 Aug 2019 20:42:01 GMT

Diabetes is more common in older adults due to age-related physiological changes, such as increased abdominal fat, sarcopenia, and chronic low-grade inflammation that can lead to increased insulin resistance in peripheral tissues. In the elderly, the diabetes guidelines recommend less aggressive glycemic control. This is due to the fact that hyperglycemia generally does not cause any acute issues. Hyperglycemia is harmful over time for the kidneys, heart, arteries, nerves, and eyes. As patients get older and life expectancy decreases, those long-term risks are not as significant or applicable.

Typical goals for diabetes management at the end-of-life are to promote comfort, control symptoms (including pain, and symptoms caused by hypoglycemia and hyperglycemia), decrease complexity of treatment, relax target glucose levels, and reduce or discontinue monitoring.

Hypoglycemia is very low blood sugar, usually <72mg/dl. Some symptoms include shakiness, dizziness, sweating, and anxiety. Terminal patients have a higher risk of hypoglycemia with reduced oral intake. Hyperglycemia is very high blood sugar, defined by some sources as >270mg/dl. Some symptoms include increased thirst, fatigue, blurred vision, and weight loss. However, since symptoms are typically more prevalent with hypoglycemia, this is more of a concern while on hospice than hyperglycemia.

The following are some general tips for management of diabetes in end-of-life.

Type 1 Diabetes: The body cannot make its own insulin. This is an autoimmune disorder typically with an early (often childhood) onset. Thus, this is also called “insulin-dependent” diabetes (not to be confused with type 2 diabetes patients that are using insulin to manage their glucose).

There is not enough evidence to support discontinuation of insulin
Simplify current insulin regimen
Sole use of sliding scale should be avoided

Type 2 Diabetes: The body either resists the effects of insulin, or does not make enough insulin to manage glucose levels appropriately. This used to be called “adult-onset diabetes”, but today more children are being diagnosed with the disorder due to the rise in childhood obesity.

If diet is controlled, no routine blood glucose checks required
Reduce or stop oral diabetic medications and monitor for symptoms
May use once daily long-acting insulin, or twice daily intermediate-acting (NPH) insulin – conservative dosing recommended, with goal to avoid unnecessarily high glucose levels
Addition of sliding scale or post-prandial regimens using rapid-acting or short-acting insulins may be considered if tighter control desired
Non-fasting levels of up to 300 mg/dL are often acceptable on hospice, as long as the patient remains asymptomatic

Steroid-Induced Diabetes

Steroids will most likely be reduced or discontinued in terminal phase and blood sugars should normalize
No need for routine blood glucose monitoring

Written by: Madeline Vallejo, Pharm. D.

References:

Diaz Rodriguez JJ. “Perspective and general approach of diabetes in palliative care” Hos Pal Med Int Jnl . 2018;2(3): 197-202.
SJ Lee, MA Jacobson, and CB Johnston. “Improving Diabetes Care for Hospice Patients” American Journal of Hospice and Palliative medicine . 2016;33(6): 517-519.
MN Munshi, H Florez, ES Huang, et al. “Management of Diabetes in Long-term Care and Skilled Nursing Facilities: A Position Statement of the American Diabetes Association” Diabetes Care . 2016;39:308-318.
K Quinn, P Hudson, and T Dunning. “Diabetes Management in Patients Receiving Palliative Care” J Pain Symptom Manage 2006;32:275-286.

ProCare HospiceCare Receives ANCC Accreditation

Tue, 09 Oct 2018 16:17:55 GMT

ProCare HospiceCare Receives Provider Accreditation by ANCC

Miramar FL – October 4, 2018 – ProCare HospiceCare is proud to announce that it has been accredited as a provider of continuing nursing education (CNE) by the American Nurses Credentialing Center’s Commission on Accreditation (ANCC), effective September 24, 2018 through March 31, 2021. ANCC is a Maryland-based nursing accreditation organization that establishes quality educational standards for nursing professionals.

The ANCC Accreditation Program identifies organizations worldwide that demonstrate excellence in continuing nursing education (CNE). Accredited organizations use evidenced-based ANCC criteria to plan, implement, and evaluate the highest quality CNE activities. As a result, health ministries, nursing organizations, employers, and continuing education enterprises rely on ANCC accreditation to call forth advanced nursing practice and improved outcomes.

“The Commission acknowledges your (ProCare HospiceCare) commitment to lifelong learning and commends you in achieving accreditation,” says ANCC Chairperson, Commission on Accreditation, Jann Balmer, PhD, RN.

“At the core of our client-centric business lies the need for hospice organizations to receive ongoing nurse training in a way that allows them to focus on the most important aspect of healthcare: the patients. ANCC accreditation validates our ongoing commitment to clinical excellence and continuing nursing education for our clients and professional nurses nationwide,” says ProCare HospiceCare’s CEO and Founder, Roger Burgess.

About ANCC

The American Nurses Credentialing Center (ANCC), a subsidiary of the American Nurses Association (ANA) , is a certification body for nursing board certification and the largest certification body for advanced practice registered nurses in the United States, as of 2011 certifying over 75,000 APRNs, including nurse practitioners and clinical nurse specialists . ANCC's nursing board certification program is one of the oldest in the USA, and many of its certifications were established before 1980, when nursing certification was still in early developmental stages.

About ProCare HospiceCare

ProCare HospiceCare consists of a highly skilled team of hospice and palliative care trained clinical pharmacists that provide 24/7/365 On-Demand Clinical Services. ProCare HospiceCare offers the most competitive pharmacy pricing and advanced technology available, while also providing flexibility and a wide-ranging scope of services to meet the clinical and cost-effective objectives of each hospice.

More information: www.ProCareHospiceCare.com

ProCare HospiceCare

Andrea Baker, Marketing Director
1267 Professional Parkway
Gainesville, Georgia 30507
800-377-1037

ProCare PharmacyCare Receives Full Mail Service Pharmacy Accreditation by URAC

Thu, 09 Jul 2015 16:13:56 GMT

The URAC accreditation process for Mail Service Pharmacy evaluated ProCare PharmacyCare's organizational quality standards; customer service, communications, and disclosure standards; mail drug management standards; and pharmacy operations standards.

"We applaud ProCare PharmacyCare on achieving URAC Mail Order Accreditation," said URAC President and CEO Kylanne Green. "In today's healthcare market, URAC accreditation provides a mark of distinction for organizations to demonstrate their commitment to quality healthcare."

ProCare Rx's Chairman, Chief Executive Officer and co-owner Roger Burgess said, "URAC accreditation validates our ongoing commitment to clinical excellence and outstanding customer service relations for our clients and their members in our mail order pharmacy. I am proud of our accomplishment, which recognizes the quality work our PPC staff undertakes on a daily basis."

ProCare Pharmacy Benefit Manager, Inc., ProCare PharmacyCare's affiliated PBM, achieved URAC pharmacy benefit management accreditation in January 2015.

About URAC
URAC, an independent, nonprofit organization is a well-known leader in promoting healthcare quality through its accreditation, education and measurement programs. URAC offers a wide range of quality benchmarking programs and services that model the rapid changes in the healthcare system and provide a symbol of excellence for organizations to validate their commitment to quality and accountability.

About ProCare PharmacyCare
ProCare PharmacyCare (PPC) is a mail order and specialty pharmacy that is patient and provider oriented and focused on optimizing drug therapies and providing member health education. PPC believes timeliness and efficiency are synonymous to providing quality services. In order to accomplish this goal, they have developed a system that provides quality assurance checks, an automated system to maximize accuracy and multiple checks for each prescription by professional pharmacists. An automated shipping and manifesting system provides fast, accurate delivery to customers. Each package is routed using the most efficient delivery method. Fulfillment locations include Miramar, Florida with additional locations in Gainesville, Georgia and Las Vegas coming online in the next few months.

More information: www.procarerx.com

ProCare PharmacyCare
Ms. Andrea Baker, Marketing Director
1267 Professional Parkway
Gainesville, Georgia 30507
800-377-1037

ProCare Pharmacy Benefit Manager Receives Full Pharmacy Benefit Management Accreditation by URAC

Thu, 09 Jul 2015 16:10:54 GMT

URAC's accreditation involved a rigorous review of ProCare Rx's patient safety, drug utilization management, formulary development, compliance, information technology, contract terms, customer service, pharmacy network, marketing, and quality improvement processes and procedures.

"By applying for and receiving URAC accreditation, ProCare Rx has demonstrated a commitment to quality healthcare," said URAC President and CEO Kylanne Green. "Quality healthcare is crucial to our nation's welfare and it is important to have organizations that are willing to measure themselves against national standards and undergo rigorous evaluation by an independent accrediting body."

ProCare Rx's Chairman & Chief Executive Officer Roger Burgess said, "A valuable company has proprietary intellectual property with the policies and procedures required to achieve its business goals. URAC accreditation validates our policies and procedures and our ongoing commitment to clinical excellence and outstanding customer service relations with our clients and their members."

About URAC

URAC, an independent, nonprofit organization is a well-known leader in promoting healthcare quality through its accreditation, education, and measurement programs. URAC offers a wide range of quality benchmarking programs and services that model the rapid changes in the healthcare system and provide a symbol of excellence for organizations to validate their commitment to quality and accountability.

About ProCare Pharmacy Benefit Manager

ProCare Pharmacy Benefit Manager is an innovative, forward-thinking national pharmacy benefit manager and healthcare information technology company in business for over 25 years. It provides a wide range of healthcare systems and services to all size employers, managed care organizations, managed Medicaid plans approved Exchange plans, insurance companies, workers compensation plans, hospices and other payers. With over 64,000 pharmacies in its national network and its affiliated mail order and specialty pharmacies, ProCare Rx is an industry leader in 100% transparent, pass-through relationships.

More information: www.procarerx.com

ProCare Pharmacy Benefit Manager
Ms. Andrea Baker, Marketing Director
1267 Professional Parkway
Gainesville, Georgia 30507 800-377-1037