Medication Use at End of Life

John Swegle, PharmD, BCPSAssociate Professor (Clinical)

University of Iowa College of Pharmacy

Mercy Family Medicine Residency

“Keep them Comfortable”

• What does this mean?– Generally

• Calm/relaxed/comfortable

• Free of pain

• At peace

– Don’t forget about the family/caregivers

• Hope is for a “good death”

General Goals

• Reduce suffering– Many involved with this

• Patient, family, healthcare provider

• Medications not always the answer– Spiritual issues

• Utilize spiritual care services

– Social issues• Utilize social workers

General Goals

• Focus on symptoms that are bothersome to the patient– Through conversations/observations

• Family wishes/perceptions– Make sure the patient is the focus of the

conversation– Must have realistic goals

• All parties need to hear the same message

General Goals

• Avoid perception of giving up– Withdrawal of unnecessary medications/turning

off devices is reasonable

• Focus is a transition of care away from a curative approach

General Goals

• Location of patient often dictates approach to care– Selection of medications– Route of administration– Aggressiveness of titration

• Need for reassessment

– Access to healthcare professional

Communication

• Patients, families, caregivers

• What to expect

• What the medications are designed to do

• What is the plan from here going forward

• Education is involved in all these steps

• Be prepared to take time

Common Symptoms Encountered

• Pain• Dyspnea• Anxiety • Nausea/vomiting• Secretions• Terminal restlessness• Fatigue

Essential Drugs for End-of-Life Care

• Medications considered essential for comfort care in all settings (at least available for use):– Morphine (opioids)

– Lorazepam (midazolam)

– Haloperidol (other)

– Antimuscarinic (atropine eye drops)

• Medications to consider:– Dexamethasone

J Palliat Med 2013;16:38-43

Various Etiologies for Pain

• Physiologic– Approximately ¾ of patients entering the terminal

phase will have pain requiring opioids

• Other types of pain– Emotional: Anxiety, depression, anger– Social: Interpersonal issues (family, loneliness,

financial)– Spiritual: Non-acceptance, abandonment, paying for

previous transgressions

General Opioid Rules

• Do not be fearful of them but treat them with respect

• There is not one agent that is better than another– Everyone responds differently– Selection takes into account other patient factors

(age, renal function, other disease states, other medications, etc)

• Working with opioids is an art with some science behind it

Myths about Opioids

• Once someone goes on morphine, it means they will die– The intent of use is for comfort care– Provide for pain free periods – Often titrated/used on PRN basis

• Respiratory depression is a common side effect

Opioids

• Main uses in palliative care:– *Pain/comfort – *Shortness of breath– Overall comfort

• Potential benefits– Sedation – Calming effect– Improvement in quality of life

Opioid Selection

• Agents commonly used for end-of-life care:– Morphine

– Hydromorphone

– Fentanyl

– Oxycodone

• Agents which are not ideal choices:– Meperidine

– Any pill form

– Any partial agonist or agonist/antagonist

Am J Kidney Dis 2003:42:217-228Drugs Aging 2007;24:761-776

Opioids

• Dosing:– Individualized and will need to be adjusted

• Some do poorly on 5 mg oral morphine

• Some require very high doses

– Determine pain needs: ongoing coverage vs. PRN use

• Often dictated by setting

• PRN use is preferred at end-of-life however realize who will be administering the drugs

Initial Opioid Dosing

• IV/SQ– If using PCA, must determine if capable of pushing the

button

– Initial dosing• Standard morphine PCA dose is 1-2 mg every 10-15 minutes

PRN– If on basal/bolus – bolus dose is typically 50-100% of hourly

basal rate

• Example:– Morphine 2 mg hourly infusion with 1 or 2 mg bolus every 15

minutes PRN

Initial Opioid Dosing

• PO/SL– Standard morphine dosing

• 2.5-5 mg MSIR every 1-2 hours PRN– Liquid morphine often used (Roxanol 20 mg/ml SL

administration)

• If on basal/bolus – bolus dose is 10-15% of 24-hour dose

• Example:– Morphine sulfate 15-15-30 over 24 hours– Bolus is typically 5 mg every hour PRN

Opioid Comparison Dosing

Medication Equianalgesic dose (parenteral)

Equianalgesic dose (oral)

Fentanyl 100mcg (single dose)

200 mcg (continuous dosing)

25 mcg/hr SR morphine 65-90 mg per

day

Hydrocodone N/A 30

Hydromorphone 1.5 7.5

Methadone Varies Varies

Morphine 10 30

Oxycodone N/A 20-30

Oxymorphone N/A 10

Opioid Adverse Effects

• Constipation – Address and prevent

• CNS: sedation, confusion• Nausea/vomiting• Urinary retention• Pruritis • Respiratory depression• Hyperalgesia

Drugs Aging 2009;26(suppl 1):63-73Canadian Family Physician 2007;53:426-427

Dyspnea

• Definition of dyspnea– Bad or difficult breathing

• Subjective symptom (similar to pain)– Many people are unable to relate to dyspnea– Unable to always correlate dyspnea with

objective findings• As with pain, focus more on what the patient tells

you rather than what you or the family may observe

Dyspnea at End-Of-Life

• Focus on the symptom and not the sign• Discuss treatment options with patient/family• Most treatable causes of dyspnea have already

been dealt with at this stage• Routine use of oxygen near death is not supported

by evidence (though some will use it)• Attempt to reduce dyspnea by non-pharmacologic

means (i.e. – fan at the bedside)

Dyspnea at End-Of-Life

• Common causes– Lung mets

– Anxiety/panic

– Secondary infection

– Pulmonary edema

– Metabolic acidosis secondary to multi-system failure

– Newly developed pleural effusion

– Anemia

Common Respiratory Medications

• Bronchodilators– Utilized in those with underlying pulmonary disorders

• Not always able to see objective improvement but the patient may claim to feel better

– Oral/nebulized/IV all are available depending on which agent is selected

• Corticosteroids– Target inflammation – Dose appropriately and be aware of objective

improvement versus “steroid effect”

Semin Oncol 2011;38:450-459

Respiratory Depressants –Bezodiazepines

• Main agents to use:– Diazepam

– Lorazepam

• Mechanism of action– Depression of hypoxic or hypercapnic ventilatory

response

– Alter the emotional response to dyspnea

• Avoid widespread use unless there is underlying anxiety

J Palliat Med 2012;15:106-114

Respiratory Depressants – Opioids

• Morphine– Most frequently used opioid for treating dyspnea

– Dosing/frequency similar to pain• Order often written PRN pain/dyspnea

– Not always useful for treating dyspnea• Similar to the idea that not all pain should be treated with

morphine

• Do not rely completely on opioids that the overall picture is ignored

Respiratory Depressants – Opioids

• Morphine:– Mechanism of action (multiple theories)

• Shifting of central PCO2 perception

– Resetting of the homeostatic control of PCO2

– Will allow the body to tolerate higher levels of CO2 without feeling respiratory fatigue

• Preload reduction

• Relaxation effect?

• Miscellaneous mechanisms

Am J Respir Crit Care Med 2011;184:867-869

Anxiety

• Culmination of physical and psychological symptoms mixed in with the reality of the situation– Psychological factors (i.e. – fears of isolation,

factors associated with death) may impact the physical findings

• Presents in many ways– Restlessness, insomnia, hyperactivity,

jitteriness, apprehension, worry

Management of Anxiety

• Attempt to identify the etiology– Example: anxiety secondary to dyspnea, delirium

– Drug-induced or drug withdrawal

– The relative from California

• Consider non-pharmacologic solutions– Other disciplines: social worker, spiritual care

– Family support

– Psychological support

Curr Opin Support Palliat Care 2007;1:50-56

Management of Anxiety

• General medications used:– Benzodiazepines

• Lorazepam 0.5-1 mg hourly PRN

• Clonazepam (similar dosing)

– Antipsychotics• Haloperidol 0.5-2 mg hourly PRN

• Quetiapine 12.5-25 mg every 2 hours PRN

– Antidepressants

Curr Opin Support Palliat Care 2007;1:50-56

Nausea

• Entirely subjective experience– Sensation which typically precedes vomiting

• Epidemiology is uncertain due to methodological challenges – Heterogeneity of patient populations, various

study settings, etc.

• Fair to say that the symptom is very disturbing

Clin Interv Aging 2011;6:243-259

Nausea

• Similar to many symptoms, it’s best to try and identify the etiology– Or at least identify the receptors you wish to target– Not always possible (multiple causes may be involved)

• Areas of involvement– Chemoreceptor trigger zone– Labyrinths– Peripheral afferents

• Do not forget the bowels

Antihistaminic Agents for Nausea

Selected Medications Comments

Diphenhydramine (Benadryl) Useful agent but sedating

Dimenhydrinate (Dramamine) Often used for “motion sickness”

Meclizine (Bovine, Antivert) Often prescribed for “dizziness”

Promethazine (Phenergan) Predominately an antihistamine but has small amount of dopamine blocking properties

Medications for Nausea

• Dopamine receptor antagonists– Work by blocking dopamine 2 (D2) receptors

– Useful group of medications for nausea• Often used as first-line for generalized nausea

– Adverse effects may be limiting factor• Dystonic reactions, akathesia, sedation

Dopamine Receptor Antagonists

Selected Medications Comments

Prochlorperazine (Compazine)

Generic dopamine blocker and preferred agent to use in many acute situations; Less sedating than promethazine

Haloperidol (Haldol) 0.5-1 mg PO/0.5 mg SQ/IV every 6-8 hours (may be more frequent administration)

Baggage associated with use; newer antipsychotics also used but tend to be more expensive

Metoclopramide (Reglan) Dual mechanism: blockade of dopamine receptors and prokinetic agent on GI tract

Medications for Nausea

• Serotonin antagonists (i.e. – ondansetron)– Block serotonin (5-HT3) receptors through

blockade of local receptors in the GI tract (primary) and will block serotonin receptors centrally (secondary)

– Key concept….. These agents are very useful for emetogenc causes which are associated with release of serotonin

Secretions

• Often distressing to caregivers/family• Precise mechanism unclear

– Generally referred to as inability to clear secretions

– Air flowing over secretions with respiration creates the noise

• The “death rattle”– Associated with death being near

Secretions – Management

• Education of family

• Non-pharmacologic– Repositioning– Suctioning

• Often short-lived benefit and may be more distressing to family

Am J Health Syst Pharm 2009;66:458-464

Secretions – Management

• Medications:– Atropine

• 1% eye drops; 1-2 drops po hourly PRN• 0.4 mg SQ/IV q4-6 hours PRN

– Glycopyrrolate • 1-2 mg po BID-TID• 0.1-0.2 mg SQ/IV every 4-8 hours PRN

– Scopolamine– Octreotide

CNS - Fatigue

• Numerous causes– Pain, medications, deconditioning, anemia,

cytokine release, metabolic abnormalities, depression, infection, dehydration

– Increased sleep is an expected outcome as end of life gets closer

• Is there a need to treat?– Is it a primary concern to the patient?– Are there reasonable options that minimize

risks?

Terminal Restlessness

• This is a one hour talk• Generally defined as unsettling behaviors in the

last few days of life• General approach:

– Look for underlying cause

– Remove or treat cause if possible (i.e. – drugs)

– Create safe environment for all parties

– Maintain patient dignity

Terminal Restlessness

• Non-pharmacologic– Comfortable environment (i.e. – music)– Familiar home objects– Involve family members– Limit room/staff change– Limit interruptions (i.e. – blood draws)– Reorienting by family or staff

Terminal Restlessness

• Pharmacologic– Haloperidol usual agent of choice

• 0.5-1 mg every 1-2 hours PRN

– Lorazepam typically second line• 0.5-2 mg hourly PRN

– Often will see combinations of these two agents used

Other Symptoms Encountered

• Depression

• Behavioral problems

• Anorexia

• Insomnia

• Family crisis situations

Discontinuing Medications

• If actively dying, stop everything but comfort meds

• And stop the monitoring…..

Concluding Remarks

• Be realistic in your expectations from drugs– Not everyone responds the same way

• Include the patient in the discussion

• More expensive medications are not always better

• Don’t wait to treat the symptoms

Questions?