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

Michelle Mikus
Dr. Michelle Mikus graduated with her doctorate of pharmacy from the Honors College at Duquesne University in Pittsburgh, Pennsylvania. While in college at Duquesne, she worked in retail pharmacy for 5 years, providing her with a background that has made her both patient oriented and efficient. Dr. Mikus has completed the Heart Failure Certification course through the University of Southern Indiana as well as the Education in Palliative and End-of-Life Care (EPEC) program through the Feinberg School of Medicine at Northwestern University. Dr. Mikus has been on the Delta Care Rx team since September 2013 as a hospice clinical pharmacist and is the pharmacy manager of ProCure Pharmacy.

Michelle Mikus, PharmD

Purple is NOT the New Yellow: A Clinical Look at Purple Urine Bags

From orange to red and all shades of yellow, most clinicians can list reasons for discolored urine. When urine appears purple, however, both patients and clinicians are taken off guard. Interestingly enough, Purple Urine Bag Syndrome (PUBS) is a very real however rare clinical phenomenon that cannot go unnoticed.

Purple urine bags are just that -the bags themselves appear to have a purple tint. The urine itself is not discolored. This happens when gram-negative bacteria that produce two specific enzymes (phosphatase and sulfatase) are present in the urine and react with PVC urinary catheters and bags. While urinary tract infections are common, especially among patients in long term care facilities, PUBS is not common since it is dependent on bacteria producing those specific enzymes.

Patients that present with PUBS are often geriatric females with a history of constipation and are catheterized. Patients most often have multiple comorbid conditions, however this could be coincidental due to the age and environment of care of the patient population from many case studies. Alkaline urine plays an important role as does dehydration. Constipation allows for an overgrowth of bacteria which introduces more potential pathogens to the body (including E. Coli). The final component of the purple color is the presence of tryptophan in the body, which when in the presence of sulfatase and phosphatase in an alkaline environment is converted to indigo (blue) and indirubin (red). When indigo and indirubin combine, they appear purple to the eye.

A purple urine bag is very apparent indication of a urinary tract infection that needs treated. If not treated quickly, septicemia can occur and outcomes can be fatal, especially considering the population this most often occurs in. By treating the underlying infection and therefore eliminating the presence of phosphatase and sulfatase in the urine, the urine bag for a catheterized patient will no longer turn purple in color when replaced.


 Submitted by: Michelle Mikus, PharmD; Hospice Clinical Pharmacist at Delta Care Rx; Pharmacy Manager at ProCure Pharmaceutical Services


 References:

  1. Lin CH. Huang HT. Chien CC, et al. Purple urine bag syndrome in nursing homes: ten elderly case reports and a literature review. Clin Interv Aging. 3:729-34. 2008

  2. Harun NS, Nainar SK, Chong VH. Purple urine bag syndrome: a rare and interesting phenomenon. South Med J. 100:1048-50. 2007

 

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Michelle Mikus, PharmD

The Opioid-Induced Hyperalgesia Phenomenon

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Morphine is the gold standard of pain relief in hospice, so anytime it is administered there is at least some degree of pain relief, right? Not always! In 1943 an interesting paradoxical reaction to morphine was being reported in peer-reviewed literature and became known as Opioid Induced Hyperalgesia (OIH). While still not fully understood, it is important to recognize that this phenomenon can occur when caring for patients that have long-term opioid use.

Clinically, OIH can present one of two ways. The first is simply hyperalgesia, which is increase response to painful stimuli. The second is allodynia, which is a painful response to typically non-painful stimuli (a feather, for example). The pain that presents is often a different quality of pain and at times is in a different location.

Most research regarding OIH has been conducted in laboratory animals and has yielded results that are linear: increased opioid use = increased OIH. Unfortunately, there is not enough human data to support this correlation, but fortunately, it does not seem to be so linear. At the center of the current discussion is whether OIH results from an increasing tolerance to opioid pain medications or from taking the medications themselves (with the medication causing the perceived pain). At this point, the only thing that is certain is that OIH is quite complex and differs among patients.

One interesting observation showed that as chronic pain patients were tapered appropriately off of opioids, a portion of the patients rated their pain the same or even better. One very preliminary study that was done to look at the cause of OIH pointed to a natural progression of chronic pain. If that proves to be true, OIH would be better stated as a natural state of hyperalgesia from chronic pain.

Managing patients with OIH is largely dependent on alternative methods of pain relief. The dose of opioid should be reduced and that alone may help reduce the experienced pain. Doses can be reduced up to 50% and if appropriate, low dose methadone can be added. Withdrawal should be avoided as this can worsen pain. Rotation from a morphine derivative to fentanyl, methadone or buprenorphine may also be effective. Ketamine has been used also. Alternative pharmacologic agents can be used in combination with a lower dose of the same opioid or a different opioid. Other pharmacologic options include antidepressants (duloxetine, tri-cyclic compounds such as nortriptyline), anticonvulsants (carbamazepine, gabapentin, pregabalin), and NSAIDs (ibuprofen, naproxen, meloxicam, diclofenac). Note that the use of carbamazepine in the management of pain is considered an off-label use of this medication. Nerve blocks and spinal cord stimulation have also been used along with cognitive behavioral therapy as non-pharmacological interventions.

Caring for patients with OIH can be a significant clinical challenge as it is not well understood yet. It is important to recognize that if a patient is in pain and a larger dose of an opioid is given that effectively manages the pain, the patient likely does not have OIH. For patients that experience an increase in pain or a different quality of pain as a result of an increased opioid dose, look to alternative pharmacologic therapies to help increase quality of life.


References: 
1. Lee M, Silverman SM, et al. A comprehensive review of opioid-induced hyperalgesia. Pain Physician. 2011 Mar-Apr;14(2):145-61. 
2. Melville N. Complexities of Opioid-Induced Hyperalgesia Poorly Understood. Medscape Multispecialty. March 31, 2015. http://www.medscape.com/viewarticle/842359#vp_1. Accessed Dec 30, 2015. 
3. Schug S. Opioid-induced hyperalgesia: What to do when it occurs? Ann Palliat Med 2012;1(1):6-7. 
4. Tompkins DA, Campbell CM. Opioid-Induced Hyperalgesia: Clinically Relevant or Extraneous Research Phenomenon? Curr Pain Headache Rep. 2011 Apr; 15(2): 129–136.

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Michelle Mikus, PharmD

Rectal Medication Seizure Management Options

In end of life care, often times the oral route of medication administration is not an option. However, it is important that seizure prophylaxis be maintained beyond the patient's ability to swallow and that treatment options are known. The good news about rectal administration of seizure medications is that many antiepileptics that patients take orally can be given rectally. In addition, the dosages of these medications do not need adjusted from oral to rectal.

Phenobarbital is one of the oldest medications used for seizure prophylaxis. This medication is weight based and also takes 4-5 hours to reach peak concentration. For that reason, phenobarbital should not be used for acute seizure episodes. Dosages are most often 1-3mg/kg orally or rectally in divided doses (1-2 times daily). Note phenobarbital is sedating.

Carbamazepine immediate release tablets can be used rectally. Ideally, the same daily oral dosage is given rectally in 6-8 small, divided doses and the crushed tablets are put in a gelatin capsule when possible. Most patients require daily doses between 800-1200mg. Note carbamazepine serum concentrations should be monitored. Carbamazepine suspensions can also be used and would need to be diluted with an equal volume of water.

Valproic acid and divalproex sodium are of the most commonly used medications for seizure prophylaxis. Fortunately, they too can be used rectally when oral administration is not possible. If using the liquid formulations, dilute with an equal volume of water. Optimal response is seen at doses below 60mg/kg/day, in divided doses.

Lastly, a lamotrigine rectal suspension can be prepared out of the immediate release or chewable tablets. This is done by crushing the tablets and mixing into 6-10mL of room temperature water. Most patients find success at a dose of 250mg twice daily.

Benzodiazepines such as diazepam and lorazepam are commonly used rectally for acute seizures and should not be excluded from this overview.

There are many reasons that a patient may need to be on an antiepileptic drug: epilepsy, brain metastases, and even disease progression, to name a few. Using the above information, management of these medications beyond the oral route is possible and dose conversions are not necessary.


References:
1. Connelly, J., & Weissman, D. Fast Fact #229: Seizure Management in the Dying Patient. Retrieved September 4, 2015, fromhttps://www.capc.org/fast-facts/229-seizure-management-dying-patient/
2. Krouwer H, Pallagi J, Graves N. Management of seizures in brain tumor patients at the end of life. J Palliat Med. 2000;3:465-475

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Michelle Mikus, PharmD

POEMS: Patient Oriented Evidence that Matters

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

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

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

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

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

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

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

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

Study Design: Retrospective review

Setting: Palliative care

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


References:

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

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

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Michelle Mikus, PharmD

Death with Dignity: An Overview & Legislative Update

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

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

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

2. Patient must be 18 or more years old.

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

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

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

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

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

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

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


REFERENCES:

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

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

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

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