Atlernate Routes of Medication Administration for End of Life Symptom Management
CHOOSING THE RIGHT ROUTE AT THE END OF LIFE - COMPARING EFFECTIVENESS, VERSATILITY, COST, AND EASE OF USE IN THE HOME SETTING
Brad Macy RN, BA, BSN, CHPN Potential Conflict of Interest Statement
I am a co-founder of Hospi Corporation and the inventor of the Macy Catheter. I may benefit financially from sales of the Macy Catheter, which is discussed in this presentation. Outline
1. Current Challenges with Symptom Management 2. Analyzing Current Standards of Practice at Home 3. Indentifying the Best Alternative Route 4. Various Routes of Medication Delivery 5. Comparing Alternate Routes of Delivery Symptom Management
How are we doing?
Kehl et al. (2013) – Large lit review -dyspnea (56.7%), pain (52.4%), respiratory secretions/death rattle (51.4%), and confusion (50.1%) [ ₁] Doing better than this but have room for improvement
SUPPORT Study (1998) - >80% patients reported the desire to die at home – only 50% died at home[ ₂]
NHPCO Facts and figures (2013- 2014) [₃,₄] GIP days increased from 2.2% (2011) to 2.7% (2012) to 4.8% (2013) – (>100% increase) >33% of hospice patients still dying in an inpatient facility Symptom Management
Institute of Medicine Report - State of End of Life Care in America (2014)[ ₅₅₅]
Patients not dying in the environment of choice
“Falling short of our goals of providing end of life care based on the needs, values and preferences of our patients”
Spending too much for end of life care Of the> 1.5 million hospice patients: • 1/3 rd die in inpatient at ~$700 per day • 2/3 rd die in home setting at ~$160 per day Analyzing Current Standards of Practice
Typical Home Hospice End of Life Scenario:
The oral route fails for a patient who wishes is to die comfortably at home
Most oral medications stopped (except SL morphine, lorazepam, atropine) For many patients this is all that is needed Not adequate for complex symptom management patients When symptoms worsen
Many commonly utilized alternate medication routes or formulations often do not work well • Transdermal, Sublingual, tablets given PR Analyzing Current Standards of Practice
When alternative routes fail Symptoms continue to worsen Patient continues to suffer Family/CG are burdened significantly
Placement in Higher Acuity Setting Often more invasive and costly medication options are utilized Patient loses choice of environment of death Analyzing Current Standards of Practice
Many medications stopped in last days Typically revert to sublingual-only meds • Morphine • Ativan • Atropine
These work well in low volumes - mild to moderate symptoms.
For more severe symptoms another route must be considered proactively Issues with Current Standards of Practice
Medications many times stopped - need careful consideration
NSAID’s Bone, inflammatory pain, fever Antiepileptics Rebound seizures, neuropathic pain, withdrawal (phenobarbital, valium, clonazepam) Anti-depressants Withdrawal, neuropathic pain Steroids Metabolic disturbances, return of numerous symptoms including pain (Liver, Bone, Inflammatory) dyspnea, fever, nausea and vomiting, seizures, bowel obstruction Analyzing Current Standards of Practice
Use of potentially ineffective transdermal route Transdermal Gels Avoid compounding for systemic drugs Skin is very effective barrier for chemical penetration No evidence base – most drugs Growing evidence - no efficacy Decreased peripheral circulation – decreased bio-availability NSAIDs – some work locally, little systemic absorption
Ativan, Benadryl and Haldol Gel Study- Very little absorption [6] Analyzing Current Standards of Practice
Use of Sublingual Route SL excellent route for continuing low dose morphine, lorazepam, atropine only Very few drugs actually absorb sublingually • Morphine (9% - 51% bio-availability) [7] • Ativan
• Atropine (variable absorption) [8] • Intensols – These are NOT sublingual Copious oral secretions inhibit absorption Large volumes will not stay under tongue • May be swallowed • Silent aspiration with larger volumes - adds to respiratory distress • Crushing tablets = (bad taste + unlikely absorption+ aspiration risk) Analyzing Current Standards of Practice
Use of Tablets or Capsules Rectally
Rectum is dry, especially near death Dry tablets = difficulty dissolving = Decreased T-max and C-max Unable to spread over rectal mucosa without water Lubricating jelly adds very little water Increased burden of care - Caregivers usually don’t like giving suppositories much less pills
Literature shows micro-enemas tend to absorb better
than suppositories [9,10] Indentifying the Best Alternative Route(s)
What is the best alternative route? Scenario: The oral route fails for a patient who wishes to die comfortably at home. Answer depends on the patients wishes, active symptoms, and symptom history. Ongoing assessment / proactive planning key to good transition Does the patient wish to die at home? What is the history of symptom types and their severity Will patient experience withdrawal if any medications are stopped? Is the patient on high doses of opioids? Are adjuvants for pain and symptom control being utilized? Based on this assessment decide; Which medications should be stopped and which continued? Identifying the Best Alternative Route(s)
An optimal route would have these qualities
Clinical Effectiveness- Evidence base for effectiveness Easy Use - Home Setting • Easy for caregivers • Comfortable and safe • Rapid initiation and availability • Minimum supply coordination. Identifying the Best Alternative Route(s)
A optimal route would also be:
Versatile - All medications needed could be given via this route - scheduled and break through dosing Cost Effective -Low comparative cost • Not always obvious Per diem pharmacy costs Delivery costs Supply costs Nursing time to implement and problem solve Alternate Routes of Medication Delivery
Sublingual Benefits Easy, Comfortable, Low cost
Downsides Limited medications Limited surface area Copious secretions inhibit absorption Limited dose volume - potential aspiration Alternate Routes of Medication Delivery
IV Benefits Fast (once placed) Very Effective Versatile medications
Downsides High CG burden Difficult/delayed access to supplies/meds High cost Some limited medications (NSAIDS) Higher complications Alternate Routes of Medication Delivery
SQ Benefits Usually fast (once placed) Usually effective Mostly comfortable
Downsides Difficult/delayed access to supplies/meds High cost Limited medications Higher complications Transdermal Benefits Easy Comfortable Downsides Poor absorption Delayed/difficult access (compounding/delivery issues) Moderate cost Very Limited medications Decreased peripheral circulation EOL No break through dosing potential Alternate Routes of Medication Delivery Intranasal Benefits Very rapid onset Easy Comfortable Downsides High cost Very limited drugs Buildup of residue Alternate Routes of Medication Delivery Rectal (Suppositories) Benefits High medication versatility Effective absorption most meds used at end of life ⁴ Some are inexpensive Less CG education Downsides Higher CG Burden Uncomfortable (requires repeated movement) Ongoing invasion of privacy Low dose versatility – usually one drug, one dose Availability and cost if specially compounded Time to onset of effect An Emerging Alternate Route Rectal micro-enema (Macy Catheter) • Device placed by the clinician • Medication port on leg or abdomen • Discreet delivery of medications in suspension via syringe to rectal mucosa • Oral medications crushed and suspended or dissolved in water • Stays in place for ongoing medication administration • Small, soft balloon defecated when patient has bowel movement (or removed prior to) An Emerging Alternate Route Rectal micro-enema (Macy Catheter) Benefits High medication versatility Effective absorption most meds used at end of life [8] Easy, Comfortable Utilizes oral medications Discreet, no caregiver invasion of privacy Quick alternative – no compounding Downsides Moderate Device Cost Device is expelled with defecation Nurse needs to reinsert Comparing Alternate Routes of Delivery Trans- Intra- Medication Versatility Rectal SQ IV SL dermal nasal Opiates - (Morphine, fentanyl, Hydromorphone, methadone, more) X X X X Fentanyl Fentanyl (Ibuprofen, Indomethacin, ASA, Ketoprofen) Local NSAIDS - X--- - Benzodiazepines (Lorazepam, Diazepam, Midazolam, Clonazepam) XXX Ativan - Midazolam (Metoclopramide, Prochlorperazine, Odansetron, Antinauseants- XXX--- promethazine) Anti Seizure - (Valproic Acid, Carbamazepine) X-X--- Sedatives - (Phenobarbital, Pentabarbital, XXX--- Anti-depressants - (Trazadone, Doxepin, Imipramine, Clomipramine) X----- Neuroleptics - (Haldol, Thorazine) XXX--- Anti-cholinergics - (Atropine, Dimenhydrate, Oxybutinin) X - X X - - Steroids - (dexamethasone) XXX--- Antibiotics - (Amoxicillin, Erythromycin, Metronidazole, Fluconizole) X-X--- Acetaminophen X-X($$) --- Furosemide X- X --- Pharmacokinetic studies have been done on the above drugs. Absorption has been found to be effective in the routes marked in green. For specific absorption via rectal route, see Davis et al. (2002) [8] Comparing Alternate Routes of Delivery Route/Formulation Dosing Versatility Drug Class Versatility Ease of Use Cost Rectal – Suppository Rectal - Macy Catheter Sublingual Subcutaneous Intravenous Intranasal Transdermal Comparing Alternate Routes of Delivery Route/Formulation Dosing Versatility Drug Class Versatility Ease of Use Cost Rectal – Suppository Rectal - Macy Catheter Sublingual Subcutaneous Intravenous Intranasal Transdermal Green - Easy and Effective for Break Through (Immediate) Symptom. and ongoing Symptom Control Yellow – More difficult for Immediate and/or ongoing Symptom Control Red – Not effective for immediate symptom control Comparing Alternate Routes of Delivery Route/Formulation Dosing Versatility Drug Class Versatility Ease of Use Cost Rectal – Suppository Rectal - Macy Catheter Sublingual Subcutaneous Intravenous Intranasal Transdermal . Green - 80%+ drug classes listed (slide 24)have drugs effective via route Yellow - 50% drug classes listed have drugs effective via route Red - 20% or less of drug classes listed have drugs effective via route Comparing Alternate Routes of Delivery Route/Formulation Dosing Versatility Drug Class Versatility Ease of Use Cost Rectal – Suppository Rectal - Macy Catheter Sublingual Subcutaneous Intravenous Intranasal Transdermal Green - Minimal Training, Easy set up, non-sterile, comfortable for CG/Pt., low complications Yellow - Minimal Training, uncomfortable for CG/Pt., repeated invasiveness Red - Greater training needs, delivery/supply management, sterile technique, more complications Comparing Alternate Routes of Delivery Route/Formulation Dosing Versatility Drug Class Versatility Ease of Use Cost Rectal – Suppository $$ Rectal - Macy Catheter $$ Sublingual $ Subcutaneous $$$ Intravenous $$$ Intranasal $$$$ Transdermal $$ $ ~ $10 dollars/day $$ ~ $20 dollars/day $$$ ~ $50 dollars/day $$$$ ~ $100/day Comparing Alternate Routes of Delivery Route/Formulation Dosing Versatility Drug Class Versatility Ease of Use Cost Rectal – Suppository $$ Rectal - Macy Catheter $$ Sublingual $ Subcutaneous $$$ Intravenous $$$ Intranasal $$$$ Transdermal $$ Green - Easy and Effective Green - 80%+ drug Green - Minimal Training, for Break Through classes listed (slide Easy set up, non-sterile, $ ~ $10 dollars/day (Immediate) Symptom. 24)have drugs effective comfortable for CG/Pt., low $$ ~ $20 dollars/day complications and ongoing Symptom via route $$$ ~ $50 dollars/day Control Yellow - 50% drug Yellow - Minimal Training, uncomfortable for CG/Pt., $$$$ ~ $100/day Yellow – More difficult for classes listed have repeated invasiveness Immediate and/or ongoing drugs effective via Red - Greater training Symptom Control route needs, delivery/supply Red – Not effective for Red - 20% or less of management, sterile immediate symptom drug classes listed have technique, more control drugs effective via route complications Review - Planning a Good Patient-centric Death 1. Provide ongoing assessment and proactive care-planning • Identify which meds can be stopped and which continued 2. Avoid symptom crises that lead to loss of patient choices and increased caregiver burden. • Quickly respond to symptom return • Consider adding back adjuvants 3. Choose the medication route that meets the needs and wishes of the patient in the easiest, most versatile, and most cost effective way possible. Cited References 1. Kehl, KA et al . A systematic review of the prevalence of signs of impending death and symptoms in the last 2 weeks of life. Am. Journal of Hospice and Palliative Care 2013 Sep;30(6):601-16 2. Pritchard RS, Fisher ES, Teno JM, Sharp SM, Reding DJ, Knaus WA, Wennberg JE, Lynn J. Influence of patient preferences and local health system characteristics on the place of death. SUPPORT Investigators. Study to Understand Prognoses and Preferences for Risks and Outcomes of Treatment ., J Am Geriatr Soc. 1998 Oct;46(10):1242-50. 3. NHPCO Facts and Figures (2014); http://www.nhpco.org/sites/default/files/public/Statistics_Research/2014_Facts_Figures.pdf 4. NHPCO Facts and Figures (2013); http://www.nhpco.org/sites/default/files/public/Statistics_Research/2013_Facts_Figures.pdf 5. Institute of Medicine Report (2014); Dying in America: Improving Quality and Honoring Individual Preferences Near the End of Life ; http://www.iom.edu/Reports/2014/Dying-In-America-Improving-Quality-and-Honoring-Individual-Preferences-Near-the- End-of-Life.aspx 6. T. J. Smith, J. K. Ritter, P. J. Coyne, G. L. Parker, P. Dodson, D. S. Fletcher, Testing the cutaneous absorption of lorazepa m , diphenhydramine , and haloperidol gel used for cancer-related nausea., Journal of Clin Oncol 2011 29: 7. Gary M. Reisfeld, M.D., George R. Wilson, M.D., Rational Use of Sublingual Opioids in Palliative Medicine , Journal of Palliative Medicine, 2007; 10:465-475, 8. Davis, MP, Walsh D, LeGrand SB, Naughton M. Symptom control in cancer patients: the clinical pharmacology and therapeutic role of suppositories and rectal suspensions . Support Care Cancer, 2002 Mar;10(2): 117-38. 9. De Boer AG, Moolenaar F, de Leede LG, Breimer DD. Rectal drug administration: clinical pharmacokinetic considerations. Clin Pharmacokinetics, 1982 July-Aug;7(4):285-311 10. Van Hoogdalem EJ, de Boer AG, Breimer DD. Pharmacokinetics of rectal drug administration, Part 1. Clin Pharmakokinet.1991;21:11-26. Related References • Coyle N, Adelhardt J, Foley KM, Portenoy RK. Character of terminal illness in the advanced cancer patient: pain and other symptoms during the last four weeks of life. J Pain Symptom Management 1990; 5:83-93. Cooper J. Stepping into palliative care; a handbook for community professionals ; Radcliffe Press; 2000; Chapter 7: 105-116. Letizia M, Shenk J, Jones TD. Intermittent subcutaneous injections of pain medication: effectiveness, manageability, and satisfaction. Am J Hosp Palliative Care 1999;16(4):585-92 Crane RA. Intermittent subcutaneous infusion of opioids in hospice home care: an effective, economical, manageable option. Am J Hosp Palliative Care 1994;11(1):8-12. David S Weinberg BA, Charles E Inturrisi PhD, Bruce Reidenberg MD, Dwight E Moulin MD, Tony J Nip BS, Stanley Wallenstein MS, Raymond W Houde MD and Kathleen M Foley MD . Sublingual absorption of selected opioid analgesics. Clinical Pharmacology and Therapeutics 1988; 44:335–342 Coyne PJ, etal. Compounded Drugs – Are customized prescription drugs a salvation, snake oil or both? Journal of Hospice and Palliative Nursing 2006;8:222-226 Moolenaar F, Koning B, Huizinga T. Biopharmaceutics of rectal administration of drugs in man. Absorption rate and bioavailability of phenobarbital and its sodium salt from rectal dosage forms, Laboratorium voor Farmacotherapie en Receptuur, Ant. Deusinglaan, 2, Groningen, The Netherlands Related References Warren DE. Practical use of rectal medications in palliative care. Journal of Pain and Symptom Management 1996;11:378-387. Nee, Douglas PharmD, MS. Rectal Administration of Medications at the End of Life.; HPNA Teleconference December 6, 2006. http:// www.hpna.org. Accessed January 2012 F. Moolenaar, S. Bakker, J. Visser, T. Huizinga, Biopharmaceutics of rectal administration of drugs in man IX. Comparative biopharmaceutics of diazepam after single rectal, oral, intramuscular and intravenous administration in man. International Journal of Pharmaceutics Volume 5, Issue 2, April 1980, Pages 127–137 Graves NM, Kreil RL Rectal administration of antiepileptic drugs in children. Pediatr Neurol .,1987; 3:321-326 Web References and Resources http://www.hpna.org/DisplayPage.aspx?Title=2012 CPF Poster Presentations “A Quality Improvement Study: Use of a Rectal Medication Administrative Device, an Intervention to Manage End-Stage Symptoms in Hospice Patients when the Oral Route Fails “- Brad Macy, RN, BA, BSN, CHPN ®; Debi Clancy, RN, BSN, CHPN ®