Download Management of Acute Pain, Nausea, and Emesis

Management of Acute Pain,
Nausea, and Emesis
Joseph Bubalo PharmD, BCPS, BCOP
Oncology Clinical Pharmacy Specialist
Assistant Professor of Medicine
Acute Pain and Nausea
Management Overview
• Assessment
• Therapeutic options
• Monitoring/management
Pain Assessment
• History of past pain medication use as well
as history of recreational or substance
abuse activity, including alcohol.
• List of current medications (RX and OTC)
and supplements (herbal, nutritional,
homeopathic, etc)
• Allergy/sensitivity History
Pain Assessment
• Location – find all locations and intensity
at each. Get an overall pain score.
• Character – sharp, dull, aching, constant,
intermittent, burning, etc.
• Frequency and pattern.
• Severity.
• Has it changed or what makes it
better/worse?
• Known etiology?
Pain Assessment
• What have they tried (pharmacologic and nonpharmacologic) and what were the results?
– Therapy, dose, duration, how results were evaluated.
• What are the patient’s expectations/goals?
• Initial evaluation and follow-up must be done a
bedside
• Follow-up over time – is a change new pain as
opposed to not enough drug?
Opioid Agonists
Drug
Onset
(min)
Peak
(h)
Duration Halflife(h)
(h)
Dose
Interval(h)
Codeine
IM 10-30
PO 30-60
0.5-1
4-6
3-4
3-6
Fentanyl
IM 7-15
IV 3-5
0.1
1-2
1.5-6
0.5-2
Hydrocodone
10-20
0.5-1
4-8
3.3-4.4
4-8
Hydromorphone
PO 15-30
0.5-1
4-6
2-4
3-6
Methadone
PO 30-60
IV 10-20
0.5-1
Acute 4-6 15-30
Chronic >8
Morphine
PO 15-60
IV <5
PO 0.5-1 3-6
IV 0.3
2-4
3-6
Oxycodone
PO 10-15
0.5-1
3-4
3-6
4-6
6-12
Equianalgesic Interchange
Agent
IM/IV/SQ
Oral
Morphine
10
30(60)
Oxycodone
N/A
30
Hydromorphone 1.5
7.5
Methadone
1-10
2-20
Fentanyl
0.1
N/A-Actiq*
Hydrocodone
N/A
30
Codeine
120
200
Meperidine
75
300
Routes of Administration
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Oral
Rectal
Transdermal
Sublingual/Buccal
Intramuscular
Intravenous
Subcutaneous
Spinal
PRN IV Opioid Equivalents
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Morphine 4 mg
Hydromorphone 0.5 mg
Fentanyl 40 mcg
Meperidine – no longer used at OHSU
PRN Oral Opioid Equivalents
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Morphine 10-20 mg
Oxycodone 10-20 mg
Lortab®-5 2-4 tabs
Lortab®-10 1-2 tabs
Hydromorphone 2-4 mg
Codeine 60-120 mg
Analgesic Therapeutics
• Start at “normal dose”
• Base frequency on severity of pain, patient
tolerance, pharmacokinetics
• If chronic analgesics minimum of 25-30%
of chronic dose for breakthrough to
achieve efficacy
• Titrate to therapeutic dose and lengthen
interval as analgesia occurs
• Consider adjuvants and co-analgesics
Duration of Therapy
• Based upon etiology …the expected
duration of pain will vary
– Somatic, abdominal, neuropathic
• Fixed pain course?
• Acute pain – Subsides over an “expected”
period of time
• Acute exacerbation of chronic pain
– Return to baseline or titrate to new baseline
Renal and Hepatically Impaired
Patient
• Choose agent with fewest active
metabolites
• Dose to effect than titrate slowly at
increased intervals
• Agents of choice - hydromorphone,
oxycodone, and fentanyl
• Contraindicated agents – meperidine,
propoxyphene
The Opioid Naive
• Assess type and duration of pain
• Analgesic doses used thus far and
response/side effects
• PCA OK, but no basal
• Frequent reassessment
• Most at risk: small, elderly, organ
compromised
Opioid Tolerant
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Chronic pain patient
Recreational user
Figure 24 hour usage
Base rescue dosing at 10% of 24 hour use
or 25-30% of incremental dose at the
normal interval
• Assess bowel function
PCA Guide
• Initial basal may be used to replace chronic
dosing otherwise leave off during initial
assessment period
• Breakthrough frequency generally 6, 10, or 15
minutes
• Choices – Morphine 1 mg = hydromorphone 0.2
mg = fentanyl 10 mcg
• Give range to allow titration for more effective
dosing
• Naloxone part of protocol orders
PCA Safety Issues
• PCA by proxy
• Patient education
– For appropriate analgesia
– To prevent oversedation
– Videogame thumb
• Monitoring
– Pain, alertness, vitals Q 4H-rate/quality of respirations
first 24-48 hours.
• Product selection
Adjuvants/Coanalgesics
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Laxatives
NSAIDs
Anti-anxiety
Antiemetics
Hypnotics
Muscle relaxants
Local anesthetics
Consider additive side effects and potential to
exacerbate co-morbidities
Opioid Side Effects
• Respiratory depression – titration rate based
on analgesic need, reduce dose if cause of
pain relieved. Rare after 3-4 days.
• Constipation
• Itching – Antihistamines or change agent.
True allergy rare
• Nausea – Antiemetics, take with food, change
agent or route
• Hallucinations – Change agent or route
• Sedation – Rule out other causes, change
agent, add stimulant
• Urinary retention – Change agent or add
bethanacol
Sick
Expulsion
Retching
Hurl
Puke
Spew
Honk
Ralph
Ow
Vomito
Gag
General Management of Nausea
Upchuck
and Vomiting
Heave
Spit Up
Blow
Chunks
Regurgitation
Upset Stomach
Barf
Emesis
Hyperemesis
Disgorgement
Throw up
OH
The First Emesis?
Assessment of N/V
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GI status – Obstructed or not
Frequency – nausea/emesis
Volume – emesis and contents
Timing – Proximate cause, worse in
AM/PM?
• Hydration status?
Assessment
• Associated Factors
– Undigested food
– Neurologic signs/headache
– Electrolyte abnormalities
– New medications (include OTC, supplements,
etc)
– Therapy – drugs, radiation, chemo,
– Phobias, anxieties, anticipatory habits
– Patient expectations
Cerebrum
Motion/space
H1, M, 5HT1a
Memory, fear, dread
Emetic center
Nucleus tractus
solitarious (NTS)
5HT3, D2, M, H1, NK1
Chemoreceptor Trigger
Zone (area postrema)
CNS
Blood brain Barrier
5HT3, D2, M, NK1
Periphery
Inner ear
Vagal and sympathetic
afferents
GI tract
Sensory input
(pain, smell, sight)
5HT3, SP
Blood born toxins
Pharynx
Local irritants
Etiologies
• Drug/treatment Induced
– Opioids, supplements, antibiotics, cytotoxics,
NSAIDs, SSRI, radiation (to GI, CNS)
• Disease related
– Gastric irritation/obstruction, constipation,
electrolyte/metabolic factors, increased
intracranial pressure, vestibular disturbances
• Psychological Factors
– Anxiety, fears, phobias, sights, odors
Therapy/Drug Selection Issues
• Drug affinity for probable cause (receptors,
pharmacodynamics, etc)
• Available routes of administration
• Side effect profile
• Patient Contraindications
• Treat underlying condition if possible
Major “Antiemetic”
Drug Classes
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Serotonin (5-HT3) receptor antagonists
Dopamine (D2) receptor antagonists
Neurokinin 1 antagonists (NK1a)
Substituted benzamides (metoclopramide)
Steroids
Benzodiazepines (BZ)
Cannabinoids
Histamine (H1) receptor antagonists
Muscarinic receptor antagonists
Agents and Issues
• Metoclopramide – GI stasis or lower
sedation level needed
• Dexamethasone – inflammatory
component, cerebral edema, additive
effect needed
• Octreotide - Bowel obstruction in terminal
disease or those who fail anticholinergics
• Benzodiazepines – anxiety, phobias,
learned behaviors
Agents and Issues
• Phenothiazines – Broadly active,
especially in combination
• Haloperidol, droperidol – similar to
phenothiazines in spectrum of activity
• Meclizine, dimenhydrinate, scopolamine –
vestibular component
• Hyoscyamine – for nausea secondary to
excess bronchial or gastric secretions
• Serotonin antagonists – Drug of last resort
Agents and Doses
• Metoclopramide 10-30 mg IM/IV/PO Q 4H PRN
(60-100 mg/day on average)
• Droperidol 0.625 mg IV/IM Q 4H PRN
• Haloperidol 0.5-2 mg Q 6 H PRN
• Prochlorperazine 2.5-10 mg IV/IM/PO Q 4H
PRN*
• Promethazine 6.25-25 mg IV/IM/PO/PR Q 4H
PRN
• Chlorpromazine 25-100 mg IV/PO Q 4H PRN
* Also have PR Option
Additional Agents
• Dexamethasone 4-8 mg IV/PO QD to QID
• Scopolamine patch 1.5 mg (up to 8 hours
for effect)
• Dimenhydrinate 12.5-25 mg IV or 25-50
mg PO Q 4H PRN
• Meclizine 12.5-25 mg q 8 H PRN
• Trimethobenzamide 200 mg IM/PR Q 6H
PRN
Serotonin(5HT3) Antagonists for
General N/V
• Ondansetron
– 4 mg IV or 8 mg PO
• Granisetron
– 0.5 -1 mg IV/PO
• Dolasetron
– 12.5-25 mg IV or 50 mg PO
All dosed one to two times daily
Additional Routes
• Sub Q
– Metoclopramide, octreotide, haloperidol,
dexamethasone, scopolamine
• Don’t give Sub-Q (cause irritation and
erosions)
– Chlorpromazine, diazepam, prochlorperazine,
promethazine, hydroxyzine
• Sublingual
– Lorazepam, hyoscyamine, haloperidol
Is Droperidol Evil?
• 03/01 UK’s Medicine Control Agency reviews
QT issues and Janssen Dc’s Droleptan® and
injectable droperidol after risk benefit
assessment
• FDA reviews drug and receives 273 reports
for 11/97-12/01 with many being duplicates
• Majority of events occurred at doses > 10 mg
• 10 deaths, 18 cardiac arrests, 6 cases of QTc
prolongation and 3 of torsades de pointes
reported at doses < 2.5mg in 30 years
• 10 Serious case reports at doses < 1.25 mg,
none of which showed a causal relationship
Horowitz BZ, et al Academy of Emergency Medicine 2002;9(6);615-8
Droperidol Effects
• Normal QTc is 440 msec males and 450
msec females
• Prolonging QTc more than 500 msec or 60
msec increases the risk for dysrhythmia
• QT prolongation  fatal arrhythmia/ cardiac
arrest
• 0.1, 0.175, and 0.25 mg/kg doses equivalent
in a 70 kg adult to 7, 12.25, and 17.5 mg
caused a 37, 44, and 59 msec QTc
prolongation respectively.
• Before 2001 warning for doses > 25 mg
causing sudden death if at risk for cardiac
dysrythmias
Lischke V, et al Anesthesia and Analgesia 1994;79:983-6
Droperidol May be evil …
However
• Droperidol is associated with QTc prolongation
• This temporal and dose dependent association
has not been proven to be related to torsades de
pointes in any type of randomized or controlled
setting
• Case reports suggest that rare cardiac events
may be associated with droperidol
administration but none are causally associated
with it’s use
• Analogous situations exist with other
medications including haloperidol,
cyclobenzaprine, and 5HT3 antagonists
Droperidol Recommendations
• Ongoing safety monitoring should occur
• Avoid use with other agents which prolong the
QT interval, change target drug metabolism, or
in patients with known cardiac dysrhythmias
• Consider ECG monitoring if elevated doses are
required or use is indicated in a patient with
known risk factors
• Use the minimum effective dose
• Consider alternative agents if doses > 5mg are
indicated
Kao LW et al Annals of Emergency Medicine 2003;41:546-58
Combinations
• D2 Antagonist
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Metoclopramide
Prochlorperazine
Haloperidol
Droperidol
Promethazine
• 5HT3 Antagonist
– Ondansetron
• Other
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Dexamethasone
Lorazepam
Dronabinol
Dimenhydrinate
Diphenhydramine
Meclizine
Scopolamine
Hyoscyamine
Trimethobenzamide
NonPharmacologic Approaches
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Decrease Milk products
Clear liquid diet
Bland diet
Decrease sources of smell (cold and room
temperature food)
• Manage anxiety
• Distraction techniques, guided imagery
• NG tube
Other Issues
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Multiple agents common
Ginger, Peppermint oil
Hydration
Acupressure
Marijuana
Results Are the Bottom Line
Thank you!