Management of Acute Pain Nausea and Emesis

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Management of Acute Pain Nausea and Emesis Powered By Docstoc
					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 Agonists
Drug            Onset      Peak     Duration Half-      Dose
                (min)      (h)      (h)      life(h)    Interval(h)
Codeine         IM 10-30   0.5-1    4-6       3-4       3-6
                PO 30-60
Fentanyl        IM 7-15    0.1      1-2       1.5-6     0.5-2
                IV 3-5
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   0.5-1    Acute 4-6 15-30     6-12
                IV 10-20            Chronic >8

Morphine        PO 15-60   PO 0.5-1 3-6       2-4       3-6
                IV <5      IV 0.3
Oxycodone       PO 10-15   0.5-1    4-6       3-4       3-6
        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
•   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
                                                                          Sick
                        Expulsion
      Retching                          Hurl         Puke

                         Honk                                      Spew


      Ralph                                                                      Ow
                                                  Vomito
                                  Gag

      General Management of Nausea
      Heave
               and Vomiting  Upchuck


                        Spit Up
    Blow                                Regurgitation
                                                            Upset Stomach
   Chunks

                 Barf
                                    Emesis
                                                            Hyperemesis
Disgorgement
                   Throw up
                                             OH
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
                                  Cerebrum                   Memory, fear, dread

        Motion/space
        H1, M, 5HT1a              Emetic center                  Nucleus tractus
                                                                 solitarious (NTS)
                                                                 5HT3, D2, M, H1, NK1
CNS                              Chemoreceptor Trigger
                                 Zone (area postrema)
Blood brain Barrier
Periphery                        5HT3, D2, M, NK1
                                                             Vagal and sympathetic
                 Inner ear                                   afferents


Sensory input                                            GI tract
(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
•   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          • Other
  –   Metoclopramide       –   Dexamethasone
  –   Prochlorperazine     –   Lorazepam
  –   Haloperidol          –   Dronabinol
  –   Droperidol           –   Dimenhydrinate
  –   Promethazine         –   Diphenhydramine
                           –   Meclizine
• 5HT3 Antagonist          –   Scopolamine
  – Ondansetron            –   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!

				
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