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 non-pharmacologic) 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 AgonistsDrug Onset

(min)

Peak

(h)

Duration

(h)

Half-life(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

Chronic >8

15-30 6-12

Morphine PO 15-60

IV <5

PO 0.5-1

IV 0.3

3-6 2-4 3-6

Oxycodone PO 10-15 0.5-1 4-6 3-4 3-6

Equianalgesic InterchangeAgent 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

• Oral• Rectal• Transdermal• Sublingual/Buccal• Intramuscular• Intravenous• Subcutaneous• Spinal

PRN IV Opioid Equivalents

• Morphine 4 mg

• Hydromorphone 0.5 mg

• Fentanyl 40 mcg

• Meperidine – no longer used at OHSU

PRN Oral Opioid Equivalents

• 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

• 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

• 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

General Management of Nausea and Vomiting

Ralph

Hurl

Spew

BlowChunks

Emesis

Upset Stomach

Barf

Spit Up

Retching

Hyperemesis

Puke

Disgorgement

Regurgitation

Expulsion

Vomito

Sick

Throw up

Heave

OH

Gag

Upchuck

Honk

Ow

The First Emesis?

Assessment of N/V

• 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

Blood brain Barrier

Chemoreceptor Trigger Zone (area postrema)

5HT3, D2, M, NK1

Memory, fear, dread

Motion/spaceH1, M, 5HT1a

Inner ear

Nucleus tractus solitarious (NTS)

5HT3, D2, M, H1, NK1

Cerebrum

GI tract5HT3, SP

Blood born toxins

Local irritants

Vagal and sympathetic afferents

Pharynx

CNS

Periphery

Sensory input (pain, smell, sight)

Emetic center

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

• 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– Metoclopramide– Prochlorperazine– Haloperidol– Droperidol– Promethazine

• 5HT3 Antagonist– Ondansetron

• Other– Dexamethasone– Lorazepam– Dronabinol– Dimenhydrinate– Diphenhydramine– Meclizine– Scopolamine– Hyoscyamine– Trimethobenzamide

NonPharmacologic Approaches

• 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

• Multiple agents common

• Ginger, Peppermint oil

• Hydration

• Acupressure

• Marijuana

Results Are the Bottom Line

Thank you!