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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, PharmD

The Opioid-Induced Hyperalgesia Phenomenon

2016 06 02 10 28 25

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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Delta Campus Pharmacy Student

Anticoagulation Bridging Chart

There are several patient specific factors that need to be taken into account when selecting an oral anticoagulant. At times, a patient may no longer be appropriate for their current anticoagulant and need to be converted to another agent. The below chart is to serve as a guide when making clinical decisions on how to convert a patient from one anticoagulant to another agent and/or safe practices for discontinuing an anticoagulant.

Drug

Bridging Required

Indication/Dosing D/C Plan for Standard Bleeding Risk Procedure D/C Plan for High Bleeding Risk Procedure
Dabigitran (Pradaxa®)

DVT and pulmonary embolism: YES

Administer 150 mg twice daily after 5 to 10 days of parenteral anticoagulation

Dabigitran to warfarin: YES

Dabigitran contributes to INR elevation; warfarin’s effect on the INR will be better reflected only after dabigitran has been stopped for ≥2 days.

Start time must be adjusted based on CrCl:

CrCl >50 mL/minute: Initiate warfarin 3 days before discontinuation of dabigitran

CrCl 31 to 50 mL/minute: Initiate warfarin 2 days before discontinuation of dabigitran

CrCl 15 to 30 mL/minute: Initiate warfarin 1 day before discontinuation of dabigitran

CrCl  There are no recommendations provided in the U.S. manufacturer’s labeling.

Warfarin to dabigitranNO

Discontinue warfarin and start dabigitran when INR is less than 2

Atrial Fibrillation: CrCl >30, 150mg BIDif CrCl 15-30 then 75mg BID, CrCl

DVT/PE: CrCl >30 150mg BID, if CrCl

CrCl ≥ 50 Stop dabigitran 2 days before procedure

CrCl 30-50 stop dabigitran 3 days before procedure

CrCl ≥ 50 Stop dabigitran 3 days before procedure

CrCl 30-50 stop dabigitran 4-5 days before procedure

Rivaroxaban

(Xarelto®)

Rivaroxaban to warfarin: YES

Typically in general practice, clinicians stop rivaroxaban and start both a parenteral anticoagulant and warfarin at the time the next rivaroxaban dose should have been taken

Warfarin to rivaroxabanNO

Discontinue warfarin and start rivaroxaban as soon as the INR is below 3 to avoid insufficient anticoagulation

Non-valvular Atrial Fibrillation: CrCl >50, 20mg QD w/ evening mealif CrCl 15-50 then 15mg QD

DVT/PE

Treatment: 15mg BID w/ food for first 21 days then 20mg QD w/ food for remaining treatment

Risk Reduction: 20mg QD w/ food

Prophylaxis after surgery:

-Hip replacement: 10mg QD for 35 days

-Knee replacement: 10mg QD for 12 days

CrCl ≥ 50 Stop rivaroxaban 2 days before procedure

CrCl 30-50 stop  rivaroxaban 2 days before procedure

CrCl 15-30 stop  rivaroxaban 3 days before procedure

CrCl ≥ 50 Stop rivaroxaban 3 days before procedure

CrCl 30-50 stop  rivaroxaban 3 days before procedure

CrCl 15-30 stop  rivaroxaban 4 days before procedure

Apixaban (Eliquis®) 

Apixaban to warfarinYES

Discontinue apixaban, and begin both a parenteral anticoagulant and warfarin at the time when the next dose of apixaban should have been taken. Then stop parenteral anticoagulant once INR reaches goal range

Warfarin to apixabanNO

Apixaban should be started when INR is < 2

Atrial Fibrillation: 5mg BID

Any two of the following:  ≥ 80 y/o,  Scr ≥ 1.5 mg/dl or ≤ 60 kg: 2.5 mg BID

ESRD on hemodialysis: 5mg BID

On hemodialysis + ≥ 80 y/o or ≤ 60 kg: 2.5mg BID

CrCl <25: Not recommended

Hip replacement: 2.5mg BID 12-24 hrs after surgery for 35 days

Knee replacement: 2.5mg BID 12-24 hrs after surgery for 12 days

DVT/PE

Treatment: 10mg BID for 7 days then 5mg BID for 6 months

Risk reduction: 2.5mg BID for at least 6 months after DVT/PE

CrCl ≥ 50 Stop apixaban 2 days before procedure

CrCl 30-50 stop apixaban 3 days before procedure

CrCl ≥ 50 Stop apixaban 3 days before procedure

CrCl 30-50 stop apixaban 4 days before procedure

Edoxaban (Savaysa™)

DVT and pulmonary embolism: YES

Oral: 60 mg once daily after 5 to 10 days of initial therapy with a parenteral anticoagulant

Edoxaban to warfarin: YES

Oral: For patients taking edoxaban 60mg once daily, reduce dose to 30mg once daily and begin warfarin concomitantly. For patients taking edoxaban 30mg once daily reduce the dose to 15mg once daily and begin warfarin concomitantly. Measure INR at least weekly and discontinue edoxaban once INR ≥2 and continue warfarin therapy

LMWH and other oral anticoagulants other than warfarin to edoxaban: YES

Start edoxaban at the time of the next scheduled dose, when transitioning from unfractionated heparin, discontinue the infusion and start edoxaban four hours later

Warfarin to edoxaban: NO

Discontinue warfarin and start edoxaban when the INR is ≤ 2.5

Atrial fibrillation: CrCl >50 and CrCl  >95 AVOID USE

DVT/PE

Treatment: CrCl>50 60mg QD after 5 to 10 days of initial therapy with a parenteral anticoagulant, CrCl 15-50  30mg QD,  CrCl

Discontinue at least 24 hours before surgery or invasive procedure Discontinue at least 24 hours before surgery or invasive procedure

Submitted by: Alisha Ensell, PharmD Candidate 2016 and Shelby Scott, PharmD Candidate 2016


References:
1. Metzger A, Nagaraj T. New Oral Anticoagulants: Clinical Parameters and Uses in Practice. Consult Pharm. 2015;30(6):329-45.
2. Lexicomp Online. Lexicomp Web site. http://www.crlonline.com.authenticate.library.duq.edu/lco/action/home

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Delta Campus Pharmacy Student

Tube Feeding Considerations in End of Life Care

Enteral feeding tubes may be helpful for nutrition support in patients that cannot eat but have a working gastrointestinal tract. Administering medication in these tubes is useful for patients that cannot take it another route, but issues can arise. This article discusses some factors that can affect medications given this route and ways to avoid common issues related to administration down a feeding tube.

The placement site of the tube can alter the medication efficacy. Most oral medications are absorbed in the small intestine. Some medications, for example antacids, sucralfate, and bismuth, act locally in the stomach and would provide minimal benefit if administered in a tube that bypasses the stomach. In addition, if medications that rely on extensive first-pass metabolism, such as opioids, beta-blockers, or tricyclic antidepressants, are administered in a tube that ends in the jejunum, they will have increased absorption and greater efficacy possibly leading to more adverse effects. First-pass metabolism is a result of the drug entering the liver after absorption in the gut resulting in much of the drug being metabolized before reaching the systemic circulation. This is taken into consideration when dosing this type of medication and if it is bypassed, by administering into the jejunum, it leads to a higher concentration of drug than intended

The tube size also plays an important part in deciding medication administration. Small bore tubes are more comfortable for the patient but are more likely to clog, especially with medication administration. Only liquid medications should be used in a Dobhoff tube to prevent clogging. Large bore tubes are less likely to clog, but it is important to know that if the tube is being used for suctioning, medications should not be given down that tube because they might be removed before absorption.

Medications should not be administered or mixed with tube feedings because they can interact and lead to negative effects. Phenytoin is the most well-known medication in this situation, decreasing blood levels of the drug up to 75% when administered with tube feeds. It is recommended to hold feedings 2 hours before and after each dose if possible. Warfarin efficacy is reduced when administered through a feeding tube and INR should be monitored more closely. Other medications can form precipitates with tube feedings, such as iron supplements and sucralfate. Liquid medications prepared as syrups can be acidic and denature proteins in the feeding, causing clumps and leading to clogs.

Liquid dosage forms are the preferred form for enteral administration of medications. Suspensions and elixirs are preferred over syrups because they are less likely to clog. Many liquid preparations contain large amounts of sorbitol which can cause GI upset or diarrhea. There are also liquid medications with high osmolality, above 1000 mOsm/kg, which will draw water into the GI tract and lead to cramping, diarrhea, or vomiting. A few examples of medications with high osmolality include acetaminophen elixir, cimetidine solution, metoclopramide hydrochloride syrup, and lithium citrate syrup.

Medications that should not be crushed include tablets that are controlled-release, enteric-coated, teratogenic, or irritants. Disrupting the controlled-release mechanism can cause toxic blood levels of the drug and enteric-coated drugs do not crush well and when mixed with water will bond together creating a clog. If the medication is teratogenic it should not be crushed for the safety of the staff. Capsules with microencapsulated pellets, such as Depakote Sprinkle and Effexor XR, can be opened and the pellets can be administered in large bore feeding tubes.

The tube should be flushed with a small amount of water both before and after medication administration. Flushing helps prevent clogs and interactions between different medications or tube feeds. Also, if medications are scheduled to be administered at the same time, they should not be given down the tube at the same time but rather administered separately while flushing the tube in between each medication. This is important because medications can precipitate or interact if given together increasing the risk of clogs or decreasing efficacy. Also, it is recommended to hold feeding for 30 minutes before and after the medication is administered if it requires administering on an empty stomach and the tube ends in the stomach. No holding is required if the tube ends in the intestine rather than the stomach.

If clogging does occur it is recommended to intervene as soon as possible by flushing with warm water. It is not recommended to try flushing with acidic liquids, such as soda or cranberry juice, because it has not shown to be more effective than water and might compound the issue by precipitating proteins from the feedings. Instead, an alkalized enzyme solution should be used. It is prepared by crushing one sodium bicarbonate 324mg tablet and one pancrelipase tablet mixed together with 5mL of water.

Overall, medication use in feeding tubes can be complicated with many different factors involved. Problems such as clogged feeding tubes and disruption of medication efficacy negatively affect both the patient and the staff. It is important to recognize why these problems can occur and to follow proper administration guidelines to prevent them in the future.


Submitted by: Alexander Fringes, PharmD Candidate 2016


References:
1. PL Detail-Document. A Stepwise Approach: Selecting Meds for Feeding Tube Administration. Pharmacist’s Letter/Prescriber’s Letter. June 2014. 
2. Williams NT. Medication administration through enteral feeding tubes. Am J Health-Syst Pharm. 2008; 65(24): 2347-57. doi: 10.2146/ajhp080155.
3. Beckwith CM, Feddema SS, Barton RG, Graves C. A Guide to Drug Therapy in Patients with Enteral Feeding Tubes: Dosage Form Selection and Administration Methods. Hosp Pharm. 2004; 39(3): 225-37.
4. Emami S, Hamishehkar H, Mahmoodpoor A, Mashayekhi S, Asgharian P. Errors of oral medication administration in a patient with enteral feeding tube. J Res Pharm Pract. 2012; 1(1):37-40. doi:10.4103/2279-042X.99677.

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Joseph Thomas, PharmD

Cognitive Screening Assessments for Dementia Patients

When it comes to assessing a dementia patient’s cognitive status, there are many different tests that can help determine the patient’s level of impairment. The purpose of these assessments and scales is to help reduce subjectivity in clinical situations. An ideal assessment should have face validity, construct validity, concurrent validity, and inter-rater reliability. Face validity means that clinicians, family members, and patients can agree that the questions are relevant and meaningful. Construct validity means that the assessment accurately tests what it was designed to measure. Concurrent validity means that the assessment can be validated by another gold standard assessment. Inter-rater reliability is when two or more raters can use the same assessment scale and get the same answers.

When it comes to dementia patients, assessments are available to test specifically for function, behavior, and quality of life, but cognition is the coveted characteristic that is attempted to be measured. The most popular cognitive screening test administered is the Mini-Mental State Examination (MMSE). This test is designed to test cognition in areas such as memory, attention, and orientation. It is limited to a low sensitivity to change and it has floor and ceiling effects. Due to copyright enforcement issues surrounding the MMSE, it has started to fall out of favor due to fear of litigation and the Montreal Cognitive Assessment (MOCA) is gaining in popularity due to their promotion of open permission to clinicians to use their assessment without paying for licensing fees or worrying about copyright litigation. The MOCA is a 30 point based assessment and it is more sensitive than the MMSE. It is also useful to assess patients with vascular dementia. It assesses executive function, memory, language, abstraction, orientation, and delayed recall.

The National Hospice and Palliative Care Organization (NHPCO) recommends the Functional Assessment Staging Test (FAST). The FAST scale is designed to evaluate patients when the MMSE cannot reflect changes in a clinically meaningful way and it identifies progressive steps of functional decline. FAST stage 7a is the minimum staging level for hospice enrollment. An assessment used to determine overall dementia severity is the Clinical Dementia Rating (CDR). It is a comprehensive interview based test that assesses memory, orientation, judgement, function, and caregiver burden. Despite being a very useful assessment, one major downside of this assessment is the amount of time it takes to administer.

With many different types of assessments available to clinicians, it is important to select and use a test properly. Many standardized assessments with demonstrated reliability for screening of dementia are available. Clinicians should understand the specifics of an assessment before administering a test. Most tests have training guides to help ensure the correct usage of the assessment. Clinicians should implement the training guides and familiarize themselves with proper administration technique to ensure the validity and reliability of the assessment.


References: 
1. Fast Fact #150. (n.d.). 
2. MoCA Montreal - Cognitive Assessment. (n.d.).
3. Sheehan, B. (2012). Assessment scales in dementia. Therapeutic Advances in Neurological Disorders, 5(6), 349–358.http://doi.org/10.1177/1756285612455733
4. Tsoi KF, Chan JC, Hirai HW, Wong SS, Kwok TY. Cognitive Tests to Detect Dementia: A Systematic Review and Meta-analysis. JAMA Intern Med. 2015;175(9):1450-1458. doi:10.1001/jamainternmed.2015.2152.

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Jessica Horsley, PharmD

Medication Reconciliation and Transitions of Care at End of Life

According to The Joint Commission, medication reconciliation is the process of comparing a patient's medication orders to all of the medications that the patient has been taking. This reconciliation is done to avoid medication errors such as omissions, duplications, dosing errors, or drug interactions. It should be done at every transition of care in which new medications are ordered or existing orders are rewritten. Transitions in care include changes in setting, service, practitioner or level of care. Accurate and complete medication reconciliation can prevent numerous prescribing and administration errors. Medication errors related to medication reconciliation typically occur at the "interfaces of care"—when a patient is admitted to, transferred within, or discharged from a health care facility. Common causes of medication reconciliation errors include inaccuracies or omission during transcription, poor documentation, communication breakdown, and workflow disruption.

Additionally, in hospice and palliative care, some patients may be too ill, injured, young, or disabled to actively participation the medication reconciliation process. Patients may need the assistance of another person (e.g., family member, significant other, surrogate decision maker) if they are overwhelmed in managing their condition, are not proficient in speaking or reading English, or face health literacy challenges that might prevent them from understanding medication use directions. When the patient is unable to actively or fully participate in the medication reconciliation process and has requested assistance from another person, involve the authorized person(s) in the medication reconciliation process. This involvement should occur at all interfaces of care . 

Medication Reconciliation Best Practices:

1. The hospice has a standardized medication reconciliation process in place that is completed and reviewed by the IDT within 5 days of the initiation of care.

a.Medication reconciliation needs to be performed at every nursing visit comparing most current medication sheet from EMR to med sheet that is in patient's home.
b.Medication reconciliation occurs at every IDT meeting where patient cases are reviewed.

2. Any discrepancies that are identified are clarified with the physician and/or pharmacy consultant within 24 hours.

3. There is a process in place to review current medications to determine which ones are related to the primary and secondary diagnosis and therefore the financial responsibility of the hospice.

a. First Verify – collect an accurate list of ALL medications the patient is taking. This becomes the “ONE TRUE SOURCE”
b. Second, Clarify – any questions about which drugs, which dose and which frequency.
c. Third, Reconcile by reviewing this list with the hospice physician and/or pharmacy consultant along with any questions or concerns in order to obtain clarification or revised orders.


4. Provide medication and medication reconciliation education to staff and consider as yearly competency.

a. Assure Staff Training includes at least the following:
        i. Ask the patient/caregiver before the first visit to collect all of the patient’s medications. 
        ii. Note any discrepancy between the prescription on the bottle and what the patient states he/she is taking. 
        iii. Ask about the use of non-prescription medications. 
      iv. Identify any combination of medications that may be contraindicated or medications that seem to be inappropriate such as those on the Beers Criteria.

5. Assure staff has access to AND a process in place to use up to date medication information and software programs to analyze medication interactions, duplication, adverse effects etc.

6. Assessment of the patient and caregiver's ability to administer medication should be done at every nursing visit so that teaching can be customized to their needs and to enhance the safety of medication administration.  Hospice staff can consult with the Delta Care pharmacist during the visit to ensure that questions are answered.

Many of these “best practices” are already in place for your hospice by using Delta Care Rx on-demand pharmacist services. Utilizing a staff properly trained for appropriate medication reconciliation with the patient or caregiver paired with the consultation and information provided by Delta Care pharmacists is an important partnership to prevent dangerous medications errors and curb symptom management issues that may be due to inappropriate medication use and interactions. Although data specifically related to medication errors in hospice and palliative care are sparse, one study found that all hospice patients had at least one medication discrepancy, with an average of eight per patient. Most commonly these discrepancies were omission of medications. Most drug interactions identified were moderately severe. Owing to the fact that polypharmacy often increases as a patient ages and/or becomes more ill, it is prudent to always perform accurate medication reconciliation at each transition of care and provide timely updates to medication profile to ensure that an accurate medication list is always at the ready.


References:
1. The Joint Commission. Using medication reconciliation to prevent errors. Sentinel Event Alert. January 2006; 35. Available from:http://www.jointcommission.org/assets/1/18/SEA_35.PDF
2. Visiting Nurses Association of America. Patient Safety: Medication reconciliation and management. VNAA Blueprint for excellence. Available from: http://0101.nccdn.net/1_5/3d0/168/33c/A-Guide-to-Medication-Reconciliation-and-Management.pdf
3. Kemp L, Narula P, McPherson M, Zuckerman I. Medication reconciliation in hospice: a pilot study. Am J Hosp Palliat Care [serial online]. June 2009;26(3):193-199. Available from: MEDLINE Complete, Ipswich, MA. 

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