Medication Management at of Lifectshp.net/uploads/3/4/0/6/34064735/curran_ho.pdf · 2016. 1. 27. · Atropine 1% eye drops 1‐2 drops SL PRN Every 6 hours PRN • Crosses BBB •

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Medication Management at End of LifeMolly Curran, PharmDFebruary 9, 2016

PGY2 Critical Care Pharmacy ResidentDepartment of Pharmacy, University Health System, San Antonio, TXDivision of Pharmacotherapy, The University of Texas at Austin College of PharmacyPharmacotherapy Education and Research Center, University of Texas Health Science Center at San Antonio

Disclosures

I acknowledge that I have no actual or potential conflicts of interest or relevant financial relationships with any commercial interest in relation to this CE.

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Pharmacist Learning Objectives:

To describe the role of medication in managing end of life symptoms

To explain medication classes important for medical management during end of life care

To formulate evidence based recommendations for managing patient symptoms at end of life

Pharmacy Technician Objectives:

To recognize the common medications used in end of life patient care

To describe the administration routes for medications used in palliative care

To convert opioid equivalencies for various analgesic medications

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Alleviate physical and emotional symptomsAchieve the best possible quality of life (QoL)

Intended effect

Relieves discomfort or suffering

Unintended effect

Hastens death?

Rule of Double Effect

Goals for Patient Care:

Strickland, J.M. (2009) Palliative Pharmacy Care.

Unjustified Fears of Double Effect

Studies evaluating adequate pain control at end of life:

No difference in survival

Studies evaluating the use of sedation at end of life:

No significant differences in survival

One study favored sedation

Use symptom relief as means of evaluation

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Cancer 1999:86:871‐77.J Palliat Med 1998;1(4)315‐28.Arch Int Med 2003;163:341‐44.

End of Life Decisions

Meet the needs of patient and family

May address multitude of concerns about care:

Stopping unnecessary interventions

Ventilator withdrawal and extubation

Aggressive or unnecessary medical therapy

Nutrition

Provide emotional and spiritual support to prepare or plan for patient death

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Patient‐Centered

Goals of Care

Plan

Spiritual needs

Family

Caregivers

Considerations

Health Provider Communication

Imminently Dying: Prioritizing Comfort

Prepare for transition to comfort care

Stop non‐essential drugs

Convert medications aimed at comfort to alternative access routes

Subcutaneous, topical, parenteral, rectal

Providing support for family, friends, caregivers

Address symptoms at end of life

Anticipatory medication orders

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What are examples of medications that may be stopped for comfort care

patients?

A. Atorvastatin

B. Lisinopril

C. Phenytoin

D. Estradiol

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Medical Symptom Management

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End of Life Symptoms

Pain

Delirium and anxiety

Terminal Secretions

Dyspnea

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End of Life: Pain Management

Many patients die with treatable pain

Up to 80%

Minimize iatrogenic sources of pain

Use patient self‐report or validated tools for assessing

Behavioral Pain Scale in ICU

Critical Care Pain Observational Tool

Nonverbal Pain Scale

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J Palliat Med. 2010; 13(5):501‐4.J Palliat Med. 2006;9:658‐65.J Pain Symptom Manage. 2007;34:227‐36.

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Pain Scale Assessment

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Am J Crit Care 2006; 15(4):420‐7.

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Pain?

Present

Controlled?

Continue current regimen

Add PRN order to anticipate increasing

pain

Uncontrolled?

If Opioid naïve:Start PRN Morphine 2‐4mg q 15 min to assess

usage

If Opioid tolerant: Review current analgesia

dosage and increase by 25‐100% depending on severity of pain

Give PRN doses as symptoms occur

Absent

Prescribe morphine as

needed (up to a 1x/hour)

Review 24 hour use and consider Infusion if >3‐4 doses needed

Adapted from Liverpool Care Pathway

Strategy for Pain Management

BMJ 2013;346:f2174.

Properties of Common Opioids

IV EquivDosing

Onset to Peak Effect, mins

Duration of Effect, hrs

Typical Adult Dose

Morphine 10 mg 20‐30 3‐4 2‐10 mg

Fentanyl 100 mcg 2‐5 0.5‐2 0.5‐2 mcg/kg

Hydromorphone 1.5 mg 20‐30 3‐4 0.5‐2 mg

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Crit Care Med 2008;36(3)953‐63.

Take Home Point #1: If pain well controlled, consider continuing current regimen orusing equi‐analgesic dose

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Opioid Metabolism: Focus on Morphine

When administered orally, undergoes 1st pass metabolism to produce: Active metabolite

Morphine‐6‐glucoronide

Inactive metabolite Morphine‐3‐glucoronide

Contributes to neurotoxicity

All opioids undergo hepatic metabolism

Metabolites are renally cleared Consider dose

reduction/decreased frequency if side effects

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Image from: http://intranet.tdmu.edu.ua/Acta Anaesthesiol Scand 1997 Jan;41(1 Pt 2):116‐22.

Alternative Routes: Sublingual Opioids

Advantages: Rapidity of onset

Bypass 1st pass metabolism

Intensity/duration analgesia

Smaller side effect profile

Non‐invasive profile

Ease of administration

Disadvantages Unpalatable

Burning sensation

Need to retain medication for minutes

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Pharmacol Res Commun 1982;14:369‐80.Am J Hosp Care 1987;4:39‐41.Am J Hosp Care 1988;5:17‐8.

McQuay et al.n = 5

Pannuti et al.n = 8

Weinberg et al.n = 10

Osborne et al.n = 10

Intervention Dose: 10 mgRetained: 5 minPopulation: Chronic opioid use

Dose: 10 mgRetained: 10 minPopulation: Advanced cancer

Dose: 15 mg tabletPopulation: Healthy volunteers

Dose: 11.7 mg tabletRetained: Until dissolutionPopulation: Healthyvolunteers

Outcomes Meanbioavailability:61% (10‐100%)

No statisticallysignificant differences

Mean absorption: 22%Mean bioavailability :9 ± 11.9%

No statistically significant difference from PO morphine (21.9% v. 20.%bioavailability)

Misc Measuredmorphine in expectorant (F = 51%)

Allowed patients to swallow SL dose confounds results

Retention time unknown

Longer Tmax and Cmax

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Pharmacokinetics: Sublingual Morphine

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Pharmacodynamics: Sublingual Morphine

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Pannuti et al.n = 8

Engelhardt and Crawford.n = 14

Intervention Dose titrated to effect Interval: Every 4 hours as needed over 5 weeksPopulation: Advanced cancer

Dose: 0.1 mg/kg solutionPopulation: Pediatric surgical patients

Outcomes Mean pain reduction (0‐10 VAS):7.8 to 2.7

Average pain scores (0‐5 rating scale)SL route: 2.3 ± 0.5IV route: 2.5 ± 0.6

Misc Statistically significant advantages:• Rapidity/intensity of analgesia• Nonsignificant reduction in

constipation/vomiting

All patients received concurrent NSAID therapy which may confound results

Alternative Routes: Sublingual Opioids

Other opioids have been studied for sublingual administration:

Methadone

Fentanyl

SL bioavailability reported is highly variable

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Take Home Point #2: If using SL opioids, avoid doses greater than 2 mL because may leak out of sublingual space

J Palliat Med. 2007;10(2):465‐75.

What is the equivalent dose of 10mg IV morphine in mcg of IV fentanyl?

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A. 30 mg

B. 30 mcg

C. 100 mcg

D. 1000 mcg

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Alternative Routes: Rectal Opioids

Highly bioavailable absorption in lower rectum bypass 1st pass metabolism

Upper rectum absorption undergoes 1st pass metabolism

Dose similar to oral opioids due to anastomses

Any immediate release tablet or solution can be given rectally

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Capc.org. Fast Fact #257J Pain Symptom Manage. 1996;11(6):378‐87.

Take Home Point #3: May give IR opioid tablets/solution/parenteral solution (<60 mL) per rectum if PO route compromised

Alternative Routes: Subcutaneous Opioids

May be administered continuously or as needed

Conversion ratio from IV:SubQ not well established

Morphine appears to be 1:1

Adverse effects include skin irritation, itching, site bleeding

Change needle if occurs

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Capc.org. Fast Fact #28Cancer. 1988;62:407‐11.

Take Home Point #4: SubQ tissue allows for absorption of up to 3mL/hr, so consider intrinsic potency of opioid if using this route

Alternative Routes: Transdermal Fentanyl

Therapeutic blood levels achieved 13‐24 hours after patch removal

Continue to release drug for up to 24 hours after removal

May not be sufficient means of pain control for patient in last hours

Absorption effected by fevers/cachexia

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Capc.org. Fast Fact #28J Pain Symptom Manage. 1996;11(6):378‐87.

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What are alternative routes you can consider in patients without IV access?

A. Subcutaneous

B. Sublingual

C. Transdermal

D. Rectal

E. All of the Above

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Pain


Terminal secretions

Dyspnea

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End of Life: Anxiety and Delirium

State of apprehension and fear

Delirium

Hyper‐ or hypo‐ active

“Terminal agitation”

No reversible causes present

May indicate distress:

Physical

Psychological

Existential

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Strickland, JM. Palliative Pharmacy Care, 2009.BMJ 2013;346:f2174.Clin Geriatr Med 20(2004)641‐67.

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Considerations in Terminal Delirium

Check medication list:

Anti‐cholinergics

Sedatives

Hypnotics

Opioids

Consider other etiologies

Withdrawal

CNS involvement

Metabolic derangements

Neuroleptics are drugs of choice for treatment:

Haloperidol

Olanzapine

Quetiapine

Risperidone

Scant data for atypical agents

QTc interval‐ consider risks and benefits

Benzodiazepines (BZD) may precipitate paradoxical response

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Capc.org. Fast Fact #60.Am J Psych. 1996; 153:231‐7.

Anxiety in Imminent Death

Common in patients facing life‐threatening illnesses

Address and identify reversible causes

Drugs: corticosteroids, stimulants, etc.

BZD monotherapy for patients with days to weeks

For patients with months, antidepressants are preferred

Consider adjunctive BZD for first weeks of therapy

Consider rebound anxiety in patients previously on oral BZD

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J Palliat Med. 2005; 8:453‐9.Capc.org. Fast Fact #145.

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Practical Considerations: Benzodiazepine

Therapy

Benzodiazepine Equivalent Oral Dose (mg) Half‐life (hr)

Alprazolam 0.5 6‐12

Lorazepam 1 10‐20

Clonazepam 0.25‐0.5 18‐50

Diazepam 5 20‐100

Take Home Point #5: If patient previously on BZD, consider equi‐potent dosing if changing route/drug (PR, IV, SubQ)

http://www.benzo.org.uk/bzequiv.htm

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Pain


Terminal secretions

Dyspnea

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End of Life: Terminal Secretions

Lose ability to clear/swallow oral secretions

Decline of gag reflex/reflexive clearing

Accumulation of tracheobronchial tree secretions

Gurgling, Crackling, Rattling

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Strickland, JM. Palliative Pharmacy Care, 2009.

Terminal Secretions: Treatment

Repositioning for postural drainage

On side

Semi‐prone

Medication therapy

Anticholinergics

MOA:

Relax bronchial muscles and open airways

Dry mucus secretion and slow ciliary passage

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Treatment: Anticholinergics

Anticholinergic drugs are divided into:

Tertiary: cross blood brain barrier (BBB)

Quaternary: do not cross BBB

Implications on side effect profile

Bind muscarinic receptors

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Strickland, JM. Palliative Pharmacy Care, 2009.Am J Hosp Palliat Med 2012;30(5)490‐8.

Anticholinergic Toxicity

AnticholinergicToxicity

Blurred visionMydriasis

Delirium

Dry skin

IleusPsychosisConfusion

Tachycardia

Hypertension

Hyperthermia

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Am J Hosp Palliat Med 2012;30(5)490‐8.

Treatment Options: Anticholinergics

Medication Dose/Route Titration Clinical Pearls

Atropine 1% eye drops

1‐2 drops SL PRN Every 6 hours PRN

• Crosses BBB• Increased risk of CNS

side effects

Scopalamine patch

1 patch (1.5 mg base delivers 1 mg drug)

Every 72 hours • Crosses BBB• Onset 6 to 8 hours• Steady‐state at 24 hours

Glycopyrrolate (Robinul®)

0.2 to 0.4 mg IV every 8 hours PRN

Up to every 6 hours

• PO absorption erratic• Can be given SubQ

Hyoscyamine 0.125 mg or 0.25 mg PO PRN

• Crosses BBB• Onset 30 min• Available in SL tablets

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Am J Hosp Palliat Med, 2012;30(5)490‐8.Strickland, JM. Palliative Pharmacy Care, 2009.

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Pharmacodynamics: Anticholinergic Therapy

Likar et al, 2008 Hugel et al, 2006

Study (n)

Randomized, no placebon = 13Terminal cancer/cognitive dysfunction

Effectiveness of symptom control in Liverpool Care Pathwayn = 72 (36 in each arm)Advanced cancer

Methods IV glycopyrrolate 0.4 mg every6 hours versus bolus scopalamine HBr 0.5 mg every 6 hours

SubQ glycopyrrolate 0.2 mg versus hyoscine HBr 0.4 SubQ followed by continuous bolus drug infusions

Outcomes Glycopyrrolate superior to scopolamine HBr over 12 hours

*Small sample size

Full response in glycopyrrolate group versus 22% in hyoscine response

*Observer bias, unbalanced populations

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Wien Klin Wocheneschr 2008;120(21‐22):649‐83.J Palliat Med 2006;9(2):279‐84.

Patient Considerations: Anticholinergics

Contraindications to anticholinergic use:

Closed‐angle glaucoma

Ileus

Caution in patients with pre‐existing delirium

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Take Home Point #6: When selecting an agent for terminal secretions, glycopyrrolate does not cross BBB and may result in less CNS effects

Am J Hosp Palliat Med, 2012;30(5)490‐8.Strickland, JM. Palliative Pharmacy Care, 2009.


Pain


Terminal secretions

Dyspnea

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End of Life: Dyspnea

Described as: Short of breath

Suffocating

Choking

Drowning

Due to: Increased respiratory

hindrance

Abnormality of respiratory muscles

Increased ventilatorydemand

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Treatment: Dyspnea

Goal: Decrease discomfort

Non‐pharmacologic strategies:

Improve air circulation

Breathing exercises

Positioning

Medications

Opioids

Anxiolytics if anxiety related

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Strickland, JM. Palliative Pharmacy Care, 2009.J Palliat Med 2012;15:106‐14.

Opioids for Dyspnea

Improve sensation of breathlessness at low doses

Exact mechanism unknown

Distinct from respiratory depression at high doses

No advantage of inhalation therapy over PO/IV

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Take Home Point #7: While most opioids may be help with dyspnea, methadone is not effective for this indication

Strickland, JM. Palliative Pharmacy Care, 2009.BMJ 2013;346:f2174.The Cochrane Database System, 2013.

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Anxiolytics for Dyspnea

Second‐line agents for dyspnea

Effective for patients with anxiety disorder

Treatment of anxiety ameliorate dyspnea

Lorazepam may be given PO, SL, or SubQ

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Strickland, JM. Palliative Pharmacy Care, 2009.BMJ 2013;346:f2174.J Palliat Med 2012;15:106‐14.

Take Home Point #8: Anxiolytics are not first line therapy for patients complaining of breathlessness

Standardizing Symptom Orders

Wide variation exists in the palliative care delivered at End of Life

Recent research has looked at Comfort Care Order Sets (CCOS)

Purpose to facilitate comfort care interventions

BEACON Trial, 2014:

Multimodal approach to end‐of‐life care increased comfort interventions

Impact of Standardized Palliative Care Order Set of End of Life Care, 2011:

Addition of order set significantly improved adherence to accepted end‐of life interventions

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J Palliat Med 2011;14(3):281‐6.J Gen Intern Med 29(6):836‐43.

Example of CCOS

Acetaminophen 650 mg PO/PR q4h PRN T>101°F

For constant pain, give _____ (suggest Morphine SR) at ___ PO BID

For intermittent pain or shortness of breath give: Morphine sulfate ___ mg PO q 2h PRN (suggest starting at 5mg)

If NPO, give morphine sulfate __ mg IV/SubQ q 2h PRN (suggest starting at 2mg)

For anxiety, give lorazepam 0.5 mg IV/PO q6h PRN

For constipation, senna/docusate 2 tablets PO QHS

For nausea/delirium, haloperidol 1 mg PO/IV q 4h PRN

For excessive secretions hyoscyamine 0.125 mg SL q 4h PRN

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J Gen Intern Med 29(6):836‐43.

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What are the potential advantages to having an inpatient palliative care order set?

A. Less wait time for medications

B. May anticipate patient needs

C. Allow for focused care on communication

D. All of the above

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Practical Considerations

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What’s on formulary?

Opioids BZDs Anticholinergics Neuroleptics

Morphine• Concentrated PO

solution: 20 mg/mL• Injection:

2‐15mg/mL• PO Solution:

2 mg/mL

Hydromorphone• Injection:

2 or 10 mg/mL

Fentanyl• Injection: 0.05 mg/mL• Transdermal: 25, 50

100 mcg

Methadone• PO solution: All floors• Injection: NONE

Lorazepam• Concentrated PO

solution: 2 mg/mL• Injection: 2, 4 mg/mL

Midazolam• Injection: 1 mg/mL• Syrup: 2 mg/mL

Diazepam• Injection: 5 mg/mL

Clonazepam• Suspension:

0.1 mg/mL• Tablet: 0.5,1, 2 mg

Alprazolam• Tablet: 0.25, 0.5, 1 mg

Glycopyrrolate• Injection: 0.2 mg/mL

Atropine• Ophthalmic Soln: 1%

Scopalamine• Patch: 1.5 mg base

Hyoscyamine• Elixir: 0.125 mg/5 mL• Tablet (SL, chewable,

PO): 0.125 mg

Haloperidol• Concentrated PO: 2

mg/mL• Injection (lactate):

5mg/mL• Tablet: 0.5, 1, 2, 5, 10,

20 mg

Olanzapine• Tablet: 2.5, 5, 7.5, 10,

15, 20 mg• ODT: 5, 10, 15, 20 mg

Quetiapine• SR tablets: 25, 50, 100,

200, 300, 400 mg

Risperidone• ODT: 0.5, 1, 2, 3, 4 mg• PO Solution: 1 mg/mL• Tablet: 0.25, 0.5, 1, 2,

3, 4

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What’s in my PXYIS?

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Opioids BZDs Anticholinergics Neuroleptics

Morphine• Concentrated PO

solution: 8ACU • Injection: All floors• PO Solution:

All floors except 9ICU

Hydromorphone• Injection:

All floors

Fentanyl• Injection: All floors

except 5ACU and PSYCH

Methadone• PO solution: 1mg/mL• Injection: 10 mg/mL

Lorazepam• Concentrated PO

solution: None• Injection: All floors

Midazolam• Injection: All floors• Syrup: NONE

Diazepam• Injection: All floors

^ICU

Clonazepam• Suspension:

None• Tablet: All floors

Alprazolam• Tablet: All floors

Glycopyrrolate• Injection: 8ACU, 8ICU

Atropine• Ophthalmic Soln: None

Scopalamine• Patch: 5ICU, 6ACU,

8ACU

Hyoscyamine• Elixir: None• Tablet (SL, chewable,

PO): 8ACU

Haloperidol• Concentrated PO::

NONE• Injection (lactate): All

floors• Tablet: 5ACU, 6ACU,

8ACU, 9ACU, 9ICU

Olanzapine• Tablet: All floors• ODT: All floors except

9WEST

Quetiapine• SR tablets: All floors

Risperidone• ODT: All floors except

5ICU, 9WEST• PO Solution: NONE• Tablet: All floors

Current as of 3‐16‐15

Medication Orders

Anticipatory orders especially important if:

Not stocked in PXYIS

STAT orders to be verified and sent by pharmacy within 1 hours

Do not call unless <1 hour

Routine orders to be verified and sent by pharmacy within 2 hours

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Final Considerations

End of life is an unpredictable process

Evaluate patient’s comfort level bedside

Medications are one part of the treatment

Anticipating end‐of‐life needs may provide more timely care for patients

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Thank You

Dr. Katie Stowers

Laurajo Ryan, PharmD

Bryson Duhon, PharmD

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Questions?

Secret CE Codes

For Pharmacists: WG8i

For Technicians: k8iC

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Medication Management at of Lifectshp.net/uploads/3/4/0/6/34064735/curran_ho.pdf · 2016. 1. 27. · Atropine 1% eye drops 1‐2 drops SL PRN Every 6 hours PRN • Crosses BBB •

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