Introduction to Management of Common Symptoms: Pain and Nausea

Introduction to Management
of Common Symptoms:
“Death I understand very well, it is
suffering that I cannot understand.”
Pain and Nausea
John A. Mulder, MD
-- Isaac C. Singer
Vice President, Medical Services
Faith Hospice
Grand Rapids, MI
Medical Director of Palliative Care Services
MetroHealth
"Not to relieve pain optimally is
tantamount to moral and legal
malpractice."
-- Dr. Edmund D. Pellegrino
Barriers to Pain Control
Definition of Pain:
“Pain is whatever the experiencing person says
it is, existing whenever he/she says it does.”
-- M. McCaffery, RN, MS, FAAN
•
•
•
•
•
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Inadequate assessment
Inadequate pain reporting
Reluctance to take opioids
Reluctance to prescribe opioids
Nurses reluctant to give opioids
Excessive regulation
78%
62%
62%
61%
52%
36%
Roenn, Ann Intern Med, 1993
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Pharmacologic Treatment of Pain
“No patient should ever wish for death
because of a physician’s reluctance to
use adequate amounts of effective
opioids.”
-- Jerome H. Jaffe
• Select the appropriate analgesic drug
• Prescribe the appropriate dose
• Administer the drug by the appropriate route
• Schedule the appropriate dosing interval
• Prevent persistent pain and relieve
breakthrough pain
(Goodman and Gilman, 1990)
Pharmacologic Treatment of Pain
Pharmacologic Treatment of Pain
• Titrate the dose of the analgesic aggressively
• Cornerstone of cancer pain management
• Prevent, anticipate, and manage side effects
• Must be individualized
• Consider sequential trials of opioid analgesics
• Should be as simple and as non-invasive as
possible
• Use appropriate co-analgesic drugs
• Equianalgesic tables must be used
• Addiction and tolerance to opioid analgesics
are rare
WHO Ladder
Step 1 Non-Opioid Analgesic Drugs
Opioid for moderate
to severe pain
 Non - opioid  Adjuvant
Non - opioid
 Adjuvant
PAIN
• Limited value in advanced pain due to
low maximal efficiency
• Acetaminophen
Opioid for mild
to moderate pain
+ Non - opioid  Adjuvant
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2
• Non-steroidal anti-inflammatory drugs
(NSAIDs)
1
2
Step 2 Opioids for Moderate Pain
Step 2 Opioids for Moderate Pain
Limited to treatment of mild to moderate
pain
Analgesic
• Dose-limiting side effects
Codeine
100
50
Hydrocodone
15
N/A
7.5-10
N/A
• Fixed combinations with acetaminophen
or aspirin
Oxycodone
Oral Dose
(mg)
Parenteral Dose
(mg)
* Not recommended for routine use:
propoxyphene (long half-life, toxic metabolite)
Codeine
(Tylenol w/Codeine # 2, 3, 4)
(Anexia, Hycodan, Lorcet, Norace, Vicodin, Zydone)
Dose ceiling: 1.5 mg/kg (90-120 mg)
• Dysphoria
• Nausea
• Constipation
Upward dose titration limited by fixed
combination with acetaminophen.
(Combination products: DEA Schedule III)
Oxycodone
Hydrocodone
(Percocet, Percodan, Tylox)
Overlap opioid: Step 2 and Step 3
Fixed combination products
• Frequently prescribed for moderate to severe
pain
• Upward dose titration limited by fixed
combination with acetaminophen or aspirin
• Combination products: DEA Schedule II
• Less toxic than codeine
• Upward does titration limited by
fixed combination with acetaminophen
• Combination products: DEA
Schedule III
Basic Rules for Narcotic Administration
• Use oral formulations if possible
• Principle of opioid monotherapy
• Start with immediate release
formulations in patients with significant
pain
• Use medications around-the-clock for
constant pain (fixed dosing)
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Basic Rules for Narcotic Administration
• Goal: Controlled Pain (4 or fewer
rescues)
• Dose Escalation: Quickly until controlled
pain
• Maximum Dose: Does not exist
• Side Effects:
– Accommodation in 7-10 days
– Treat aggressively
– Bowel regimen
Morphine
(MS Contin, MSIR, Roxanol, Avinza, Kadian)
• Most commonly used Step 3 opioid
• Multiple dosing forms
Morphine sulfate in Contin delivery
system
Step 3 Opioids for Mod. to Severe Pain
Analgesic
Oral Dose
Parenteral Dose
(mg)
(mg)
Morphine
15
5
Oxycodone
10
N/A
Hydromorphone
Fentanyl
4
1.5
25 mcg/h q 72 h
25 mcg
Oxycodone
(OxyContin, OxyFast, OxyIR, Roxicodone)
Oxycodone in AcroContin delivery system
Should not be cut, crushed, or chewed
• No apparent dose ceiling
• May be less toxic than
morphine
Should not be cut, crushed, or chewed
Hydromorphone
(Dilaudid)
• Oral use hampered by lack of
controlled-release formulations
Transdermal Fentanyl
(Duragesic)
• Patch Size: 12.5, 25, 50, 75 and 100 mcg
• Duration of Action: 72 hours
• Advantages:
• Easy, convenient use
• No need to remember to take meds
• Disadvantages:
• Difficult when using high dose of narcotics
• Thin patients with little subcutaneous tissue
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Fentanyl Patch Indications
•
•
•
•
Patients unable to take oral medications
Non-compliant patients
Question of drug abuse
Question of cognition
Titration Schema
Transmucosal Fentanyl
(Fentora, Actiq)
• Strengths (Fentora): 100, 200, 300,
400, 600, 800 mcg
• Advantages:
• Rapid onset
• Easy to use
• Can be used in patients who cannot
swallow
Narcotic Equivalence
Initial Fixed and Rescue Dose
• 10 mg Morphine = 2.5 mg Hydromorphone =
10 mg Hydrocodone = 7.5 mg Oxycodone =
Controlled Pain
100 mg Meperidine = 120 mg Codeine
Moderate Pain
Severe Pain
• 1 mg sc/im/iv = 3 mg po
• 100 mg/d Morphine = 50 mcg/h Fentanyl/72h
No Change
25% Increase
50% Increase
Unwarranted / Exaggerated Fears
• Respiratory Depression
Prescribe the Appropriate Dose
• Addiction
• Based upon pain intensity and current
analgesic therapy
• Rapid Tolerance
• No one optimal dose
• Regulatory Reprisal
• No one maximal dose
• Appropriate dose: pain relief
throughout dosing interval without
unmanageable side effects
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Schedule the Appropriate Dosing Interval
• Prevent pain recurrence
• Minimize number of daily doses
• Depends on opioid and route
• End-of-dose failure:
• Increase dose
• Keep same interval
Notable Quotes
Famous Vomiting in Literature
"One of the best temporary cures for pride and affectation is
seasickness; a man who wants to vomit never puts on airs.”
Josh Billings 1860
"The act of vomiting deserves your respect. It's an orchestral
event of the gut.”
Mary Roach, Packing for Mars: The Curious Science of Life
in the Void
"Oh, my God! I'm gagging and vomiting at the same time.
I'm... I'm gavomiting!"
Dr. Cox, Scrubs
Famous Vomiting in Politics
"As a dog returneth to his vomit, so doth a fool return to his
folly."
Proverbs
Famous Vomiting in Sports
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Historical Remedies
Vomiting in Pop Culture
Bloodletting
Ginger
Mint
Frankincense
Etiology of Nausea
1) Chemoreceptor Trigger Zone
2) Vestibular
3) Cortex
4) GI/peripheral pathways
Identify Potential Reversible Causes
* Drugs (chemo, opioids, abx, NSAIDS, SSRIs)
* Constipation
* Gastroparesis
* GERD
* Uremia
* Pain
* Infection
* Dehydration
* Electrolyte imbalance (high Ca)
* Endocrine dysfunction
* Increased ICP
* Anxiety
Assessment
Onset
Frequency
Relationship to eating
Relationship to meds
Current anti-emetics
Chronic vs. Progressing
Alleviating factors
Severity (scale: 1-10)
Goal
Other Causes
* Pregnancy
* Cyclic Vomiting Syndrome
* Hepatic disease
* Migraine headaches
* Following surgery
* Myocardial infarction
* Violent coughing
* Hangover
* Meniere's disease
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• Most patients have multi-factorial causes
Non Pharmacologic Treatment
Non-pharmacologic Treatment
* Correct dehydration, electrolyte disturbances
* Reassurance/relaxation
• * Constipation regimen
• * Decompress
Non-pharmacologic Treatment
* Oral hygiene
* Decrease portions, use cold food
* Decrease or cease tube feedings
Non-pharmacologic Treatment
* Avoid odors
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Matching Etiology with Mechanism
Matching Medication to Mechanism
D2 Antagonists: Haldol, Reglan, Compazine, Thorazine
1) Chemoreceptor Trigger Zone
2) Vestibular
3) Cortex
4) GI/peripheral pathways
1) D2 and 5HT3 antagonists
2) Antihistamines and Anti-muscarinics
3) Antihistamines and Anxiolytics
4) D2 and 5HT3 antagonists
5HT3 Antagonists: Zofran, Emend, Remeron
Anti-histamines: Benadryl, Phenergan, Antivert, Cyclizine
Anti-cholinergics/anti-muscarinics : Hyoscyamine,
Scopolamine
Pro-motility: Reglan, Propulsid
Others: Decadron, Ativan
Opioid-Induced
Chemotherapy-Induced
• Primarily hits CTZ
Consider opioid-rotation
Think D2 Antagonist:
Reglan, Haldol, Compazine, Thorazine
Malignant Bowel Obstruction
Primarily from stimulation of CTZ
• Primarily from 5HT3 stimulating
gut/peripheral pathways
Think 5HT3 antagonists: Zofran, Emend, Remeron
Motion-Induced
Primarily from stimulation of vestibular system
Think D2-antagonist: Reglan, Haldol
Think anti-muscarinics: Scopolamine, Hyoscyamine
Don't forget to decompress
Think anti-histamines: Antivert, Phenergan
Remember Decadron
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Increased ICP
Most patients have multi-factorial causes
Directly stimulates the Vomiting Center
Steroids act to decrease pressure
Think anti-histamines
Dosing
Intractable Vomiting
• "Go hard or go home"
Appropriate doses... scheduled around-the-clock
Poly-Drug Regimens and Routes of
Delivery
ABHR (Ativan, Benadryl, Haldol, Reglan)
General guidelines:
Can be given topically, orally or rectally
* Avoid use of more than one drug from each class
* Consider less traditional medications: Decadron, Ativan
But does it work?
* May need to consider alternate routes: topical, rectal, SQ
* Be alert for drug interactions
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Continuous Infusions
• Have the potential to provide very quick
and effective relief of intractable nausea
Acupuncture / Acupressure
In nausea, stimulation of point MH6
(forearm) is believed to offer relief.
Benadryl/Ativan/Decadron (BAD drip): (0.2-2.0 ml/hr)
(50 cc D5W, 200 mg Benadryl, 8 mg Ativan, 20 mg Decadron)
Reglan/Benadryl/Decadron (RBD drip): (0.5-1.5 ml/hr)
(50 cc NS, 80 mg Reglan, 100 mg Benadryl, 8 mg Decadron)
Could consider Haldol/Ativan/Decadron, or Reglan/Ativan/Decadron
Non-traditional Meds
Marijuana
Bendectin (pyridoxine/doxylamine)
Anti-histamine, sedating
NO evidence of causing birth defects
Propulsid (cisapride)
5HT4 Agonist
Prolonged QT
Available only for "compassionate use"
• Active ingredient: Nine-delta-tetrahydrocannabinol (THC)
Demonstrated effectiveness in:
Amelioration of nausea and vomiting
Inducement of hunger in settings of chemotherapy and AIDS
Analgesia
Lowering intra-occular pressure
? Multiple Sclerosis
? Depression
Ginger lollipops
Legal Issues:
• Michigan Law vs. FDA
On Dec.4, 2008, the Michigan Medical Marihuana Act was
enacted into law allowing patients with debilitating medical
conditions such as HIV, cancer, and Hepatitis C to legally
possess and use marijuana.[69]The patient can have up to
two and a half ounces of usable marijuana and twelve plants
that are kept in an enclosed and locked facility.[70]
Tetrahydrocannabinol
Dronabinol (Marinol) - a Schedule III drug
Nabilone (Casemet) - a Schedule II drug available in Canada
Sativex (THC + canabidiol) mouth spray for M.S. patients
Cannabis is classified as a Schedule I drug under the federal
Controlled Substances Act of 1970 and is deemed to have a
high potential for abuse and no legitimate medical uses
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Random Thoughts
Successful Strategies
* Reglan (metoclpramide) 1st drug of choice: has GI
effects and CTZ effects
Attempt to identify the most likely etiology and mechanism involved
* Haldol is a great anti-emetic
Choose the medication based on that mechanism
* Steroids too
Dose appropriately and on a scheduled basis
* NG tube may be necessary
* Combination drugs of different mechanisms may be
helpful
* Anticipatory dosing most beneficial
* Use of 5-HT3 antagonists of questionable benefit in
non-chemotherapy-induce N/V
If ineffective, consider multi-drug regimens
Consider continuous infusions (RBD, BAD)
Consider less traditional interventions/medications
John Mulder, MD
616-293-3615
[email protected]
http://palliativematters.blogspot.com
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