Best Dx/Best Rx: Pain

From: Subject: Best Dx/Best Rx: Pain Date: Wed, 3 Jun 2009 21:25:53 -0700 MIME-Version: 1.0 Content-Type: multipart/related; type="text/html"; boundary="----=_NextPart_000_01B9_01C9E491.E02D0F10" X-MimeOLE: Produced By Microsoft MimeOLE V6.00.2900.5579 This is a multi-part message in MIME format. ------=_NextPart_000_01B9_01C9E491.E02D0F10 Content-Type: text/html; charset="Windows-1252" Content-Transfer-Encoding: quoted-printable Content-Location: http://www.acpmedicine.com/acp/newrxdx/rxdx/dxrx1114.htm Best Dx/Best Rx: Pain

Pain =

Alan C. Carver, MD
Mount Sinai School of = Medicine=20

Defin= ition/Key=20 Clinical Features
Best = Tests
Best = Therapy
Best = References

Definition/Key=20 Clinical Features

May be of physical or = psychological=20 origin
Acute pain is the most = common symptom=20 for which patients seek medical evaluation
Prevalence in cancer = patients, ~=20 14%=96100%; prevalence in AIDS patients, ~ 30%=9690%
Undertreatment is a = significant=20 clinical problem

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Best=20 Tests

Pain history=20
- Onset
- Temporality and presence of breakthrough = pain
- Location
- Quality of pain
- Intensity: validated scales can help = evaluation=20
  - Numeric Pain Intensity Scale
  - Visual Analog Scale
  - Faces Pain Scale for Adults and Children=20
- Aggravating/relieving factors
- Associated symptoms
Response to current and previous treatment = approaches=20
Patient's psychological state
- Stress=20
- Clinical depression
- Anxiety=20
- Mental status
Impact of pain on quality of life, including = social,=20 psychological, and spiritual well-being=20
- Medical Outcomes Study 36-Item Short Form=20 (SF-36)=20
- Sickness Impact Profile
Impact of pain on life functions=20
- Work, family, social responsibilities or = relationships=20
- Activities of daily living
- Other important activities
- Eating and sleeping
- Brief Pain Inventory
Past medical history
- Acute and chronic conditions that may cause = pain=20
- Substance abuse and/or dependence =
Comprehensive physical examination=20
- Pain behaviors=20
  - Abnormal gait or posture
  - Guarding
- Signs of systemic illness=20
- Neurologic exam
Diagnostic tests appropriate to the = pain-causing disease=20 processes
Patient expectations and goals regarding pain = intensity,=20 daily function, quality of life

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Best=20 Therapy

Individualize therapeutic approach
Refer to pain specialist or multidisciplinary = team when=20 appropriate
Provide continuity of care throughout = evaluation and=20 treatment
Reassess patient's pain complaints and = response to=20 therapy
Choose the simplest approach before more = complicated and=20 invasive techniques
Involve patient in therapeutic choices
Titrate doses to maximize efficacy and = minimize side=20 effects
Anticipate and treat side effects
World Health Organization analgesic ladder: = effective in=20 70%=96100% of adult patients=20
- Step One: for mild pain
  - NSAIDs and acetaminophen
- Step Two: for mild to moderate pain
  - Weak opioids (e.g., codeine, = hydrocodone)=20
  - Combination analgesics (e.g.,=20 oxycodone/acetaminophen) plus NSAID and adjuvants as needed =
- Step Three: for severe pain
  - Potent opioids (e.g., morphine, methadone, = hydromorphone, fentanyl) plus NSAID and adjuvants as needed =
Use adjuvant medications at any level of the = WHO=20 ladder=20
- Corticosteroids (the most widely used=20 adjuvants)=20
- Antidepressants, anticonvulsants, and other = agents for=20 neuropathic pain=20
- Bisphosphonates and radionuclides for bone = pain=20
- Antibiotics for pain from ulcerating tumors=20
Nonpharmacologic adjuvant therapy
- External-beam radiation
- Neurosurgical ablative procedures
- Psychiatric therapy
- Anesthesia

Opioids

Indications=20
- Acute pain
- Trauma-related pain=20
- Postoperative pain=20
- Cancer pain=20
- Some chronic noncancer pain (e.g., = osteoarthritis, low=20 back pain, neuropathic pain)
Choice of agent
- Based on drug and patient characteristics =
- Morphine plus gabapentin may be more = effective for=20 neuropathic pain than either agent alone=20
- Failure of response to an adequate trial of = one opioid=20 should be followed by an adequate trial of another opioid =
Administration=20
- Oral or transdermal
  - For systemic treatment of chronic = conditions if=20 possible
- Intravenous=20
  - Rapid titration and onset of = analgesia=20
  - Avoids first-pass hepatic = degradation=20
  - Yields higher bioavailability and = opportunity to=20 reduce total dose=20
  - May provide consistent level of analgesia =
  - Useful alternative for patients unable to = take=20 orally=20
  - Increased risk of systemic side = effects=20
- Subcutaneous injection=20
  - When small fluid volumes sufficient to = deliver=20 prescribed dose=20
  - Rapid titration and onset of = analgesia=20
  - Shortened duration of effect requires = continuous=20 infusion or frequent redosing to maintain constant pain relief =
  - Risk of side effects is greater than with = oral route=20
- Rectal=20
  - Absorption and first-pass metabolism = varies=20
  - Cannot be used in patients with diarrhea,=20 transmucosal lesions, neutropenia, or severe = thrombocytopenia=20
- Transdermal=20
  - When oral route is unavailable=20
  - Limited by available skin surface=20
  - Not effective for fluctuating pain = levels=20
- Intramuscular: avoid because of erratic = absorption and=20 associated pain
- Patient-controlled analgesia (PCA)
  - For initiation of parenteral opioid = therapy, rapid=20 opioid titration, or treatment of incident pain=20
  - Continuous infusion may be programmed to = supplement=20 PCA doses, enabling sleep and covering baseline pain=20
  - Equivalent or superior analgesia with the = following=20 advantages:
    - Less total opioid consumption=20
    - Fewer side effects=20
    - No greater likelihood of = dependence=20
    - May be used in the home =
- Intraspinal
  - For patients requiring large doses=20
  - Only for patients who have had pain relief = but=20 intolerable side effects with other regimens=20
  - Achieves analgesia at significantly = smaller doses=20 than with systemic administration=20
  - Intrathecal morphine is 100 times more = potent than=20 I.V.=20
  - Epidural morphine is 10 times more potent = than=20 I.V.
Duration of action
- Long-acting and sustained release for = patients in=20 continuous pain, as in cancer
- Around-the-clock administration may improve = outcomes=20 and adherence=20
- Short-acting formulations to manage = intermittent and=20 breakthrough pain
Dosing=20
- Begin with immediate-release oral agent with = a short=20 half-life for 24=9648 hr and monitor consumption, efficacy of pain = relief, and=20 side effects=20
  - Patients in severe pain may need rapid = titration of=20 a potent opioid via continuous I.V. infusion
- Long-acting or sustained-release forms may = be=20 prescribed once titration to optimal dose is achieved=20
- Change doses in increments of one third to = one half=20 the prior dose=20
- Reduce or eliminate dose gradually (in = increments <=20 25% of daily dose) if patient becomes pain free
- Short-acting, immediate-release opioids to = cover=20 breakthrough pain for patients on long-acting therapy
  - Single rescue doses of 10%=9620% of total = daily dose=20 or 25%=9630% of single standing dose=20
  - Adjusted as appropriate for the = individual=20
  - Where possible, use the same agent for = standing and=20 breakthrough medications
Conversion=20
- Inflammatory or neuropathic pain may be = better treated=20 with adjuvant analgesics than with modification of opioid = therapy=20
- Pain of opioid side effects may only need = treatment of=20 the adverse effect=20
- Refractory pain or intolerable side effects = may=20 require conversion in these settings:=20
  - Pain is opioid responsive=20
  - Current drug was titrated to maximal = effect=20
  - Side effects are already optimally managed =
- Choice of opioids may be based on patient's = past=20 experience with opioids of a given class or receptor profile=20
- Equianalgesic conversion tables should be = consulted to=20 arrive at a starting point for dosing=20
- If patient is receiving multiple opioids, = conversion=20 should be based on total dose of all prior agents, expressed as = morphine=20 equivalents=20
- If conversion is prompted by intolerable = side effects=20 but pain control is adequate, the calculated dose should next be = reduced by=20 ~ 25%=9650%=20
- If conversion is prompted by inadequate = analgesia, the=20 new agent may be started at or near an equianalgesic dose=20
- Provide additional short-acting opioids = during=20 titration of new drug for breakthrough pain=20
- Reassess pain and total daily dose for the = first 2 wk=20 after conversion, with titration of extended-release and = breakthrough doses=20 as appropriate=20
- Avoid inadequate pain control and excessive = narcosis=20 during conversion
Side effects
- Sedation
  - Occurs with onset of therapy or increase = in dose;=20 usually resolves within 3=967 days
  - Of concern in the elderly and those taking = concurrent sedating medications
  - Eliminate nonessential sedating = medications
  - Use stimulants (e.g., caffeine, = methylphenidate) for=20 cancer patients with significant persistent sedation
    - Use with caution in the elderly
    - Not recommended for patients with = sedation due to=20 opioid management of chronic pain
- Nausea
  - Frequently resolves shortly after = treatment onset=20
  - Antiemetics during first 1=962 days of = opioids may=20 help
    - Ondansetron, 4 mg I.V.
    - Prochlorperazine, 5=9610 mg = t.i.d.=96q.i.d.
    - Hydroxyzine
      
      May alleviate centrally induced nausea =
      Dose: 25=96100 mg = t.i.d.=96q.i.d.
    - Metoclopramide
      
      May reduce nausea caused by slowed = gastric=20 motility
      Dose: 10 mg q.i.d.; maximum daily = dose, 500=20 =B5l/kg
    - Scopolamine
      
      May alleviate motion-exacerbated = nausea in=20 ambulatory patients
      Dose: transdermal, 1.5 mg = postauricular patch q.=20 3 days
      May have significant anticholinergic = side=20 effects, particularly in the elderly =
- Constipation
  - Does not improve with time
  - Often underdiagnosed
  - May lead to anorexia, vomiting, abdominal = pain,=20 obstruction, impaction, and perforation
  - Appropriate dietary changes
  - Assess for constipation in patients on=20 around-the-clock opioids
  - Stool softeners and stimulant laxatives=20
- Respiratory depression
  - Rare side effect in opioid-naive patients = receiving=20 large doses and in head injury or pulmonary disease
  - Monitor sedation level and respiratory = status during=20 first 24 hr of therapy in opioid-naive patients
  - Stop opioids until depression resolves, = then resume=20 at 75% of previous dose
  - Spirometry and oxygen may be useful =
  - Treat severe respiratory depression with = I.V.=20 naloxone
    - Dose: 2 mg I.V. in 500 ml normal saline = or D5W=20
- Confusion
  - Occurs primarily in high-dose or prolonged = opioid=20 therapy and in decreased renal function
  - Patients with previous cognitive = impairment at=20 additional risk
  - Symptoms include delirium, agitation, = myoclonus,=20 hyperalgesia
  - Of particular concern in the elderly or = those with=20 concurrent CNS disease
  - Nonessential medications with CNS effects = should not=20 be prescribed for elderly patients requiring opioid therapy =
  - Neuroleptics may be useful against = confusion, mental=20 clouding, or persistent delirium
- Pruritus
  - Diphenhydramine, 25=9650 mg q. 4=966 hr =
  - Hydroxyzine, 25=96100 mg = t.i.d.=96q.i.d.
- Myoclonus
  - Clonazepam, 0.5 mg t.i.d.; increase by = 0.5=961 mg q. 3=20 days to maximum of 20 mg/day
Tolerance
- A higher dose of agent is required to = maintain a given=20 effect
- There is no clinical limit to tolerance =
- Rarely develops in stable disease
- Increasing requirements for previously = controlled=20 chronic pain should prompt comprehensive evaluation =
Physical dependence
- A withdrawal syndrome could be produced by = the=20 following:=20
  - Abrupt cessation of drug administration =
  - Rapid reduction in dose
  - Decreasing blood level of drug
  - Administration of an antagonist or mixed=20 agonist-antagonist
- Universal with prolonged opioid therapy =
- To avoid withdrawal, all patients receiving = opioids=20 for ≥ 1 wk should have drug tapered rather than abruptly = discontinued=20
Psychological dependence (addiction)=20
- Differentiate from physical dependence =
- Impaired control over drug use, compulsive = use,=20 continued use despite harm, and craving
- Extremely low prevalence in patients taking = opioids=20 for pain relief
- Pseudoaddiction
  - More common than true addiction
  - Patients with poorly managed pain mimic = signs of=20 psychological dependence
    - Drug seeking
    - Increased focus on obtaining medications =
    - Possibly illicit drug use or deception=20
  - Behaviors resolve with effective pain = management=20
  - May be exacerbated by curtailing of opioid = therapy=20

NSAIDs and Acetaminophen

No tolerance or physical dependence
Indications
- Especially useful for muscle and joint, = bone, dental,=20 postoperative, and inflammatory pain
- May suffice for mild or moderate pain =
- For severe pain, may be added to an opioid = regimen for=20 opioid-sparing effect and enhanced pain relief
Ceiling effect for analgesia
NSAID side effects
- GI symptoms
- GI bleeding
- Hypersensitivity
- Kidney dysfunction
- CNS effects
- Often dose dependent
NSAIDs may be used with GI-protective drugs =
Use acetaminophen with caution in patients = with liver=20 disease

Corticosteroids

Indications=20
- Cancer pain
  - Pain of spinal cord compression
  - Increased intracranial pressure
  - Superior vena cava syndrome
  - Metastatic bone pain
  - Neuropathic pain secondary to infiltration = or=20 compression by tumor
  - Hepatic capsule distention =
- High doses for inpatients with advanced = disease in=20 acute pain crisis
- Pain related to musculoskeletal conditions=20
Oral or injectable
Side effects
- Well tolerated for short-term treatment =
- Toxicities
  - Often arise with prolonged high-dose = therapy
  - Adrenocortical insufficiency
  - Hypertension
  - Immune suppression, masking of signs of = infection=20
  - Glaucoma
  - Electrolyte imbalances
  - GI ulceration and/or bleeding
  - Osteoporosis and/or pathologic fracture =
  - Psychiatric disturbance or psychosis =
- Avoid withdrawal syndrome upon = discontinuance=20

Antiepileptic Drugs

Indications=20
- Adjuvants for neuropathic pain
  - Peripheral diabetic neuropathy
  - Postherpetic neuralgia
  - Reflex sympathetic dystrophy
  - Trigeminal and glossopharyngeal neuralgia =
  - HIV neuropathy
  - Spinal cord injury=96related dysesthesias=20
- Postlaminectomy pain
- Phantom limb pain
- Cancer pain
Gabapentin: first-line treatment for = neuropathic pain=20
- Well tolerated (except for cognitive effects = in the=20 elderly)=20
- Side effects: sedation, nausea/vomiting, = dizziness=20
- Dose: 100 mg p.o., q. 8 hr (maximum, 3,600 = mg/day in=20 divided doses)
Carbamazepine
- First-line treatment for trigeminal = neuralgia
- Second- or third-line agent for other = neuropathic pain=20 conditions
- Dose: 50=9660 mg/day
- Monitor for hyponatremia and leukopenia =
- Use only if gabapentin has failed or is not = tolerated=20
- May cause thrombocytopenia or liver damage=20
Topiramate: adjuvant analgesic for neuropathic = pain=20
- Dose: 100=96200 mg/day
- Must be titrated slowly (no faster than 25 = mg/wk) to=20 decrease side effects such as cognitive slowing and paresthesias=20

Tricyclic Antidepressants (TCAs) =

Indications=20
- Adjuvants for neuropathic pain
  - Painful diabetic neuropathy
  - Postherpetic neuralgia
  - Chronic facial pain
  - Central pain
- Adjuvants for chronic pain
  - Cancer pain
  - Chronic low back pain
  - Osteoarthritis
Efficacy: comparable to antiepileptics
Amitriptyline: alternate choice
- Strongest anticholinergic profile
- Given at bedtime
Nortriptyline: alternate choice
- Less anticholinergic effect
- Better choice for older patients =
Imipramine: alternate choice
Dose for TCAs: 10=9625 mg, to maximum of 150 = mg/day, if=20 tolerated
Side effects of TCAs: elderly are most = susceptible=20
- Sedation
- Hypotension
- Constipation
- Urinary retention
- May cause lethal cardiac arrhythmias at very = high=20 doses (contraindicated in patients with conduction = abnormalities)=20

Selective Serotonin Reuptake Inhibitors=20 (SSRIs)

Useful in managing neuropathic pain=20
Second-line choice for refractoriness or poor=20 tolerability with other agents
Paroxetine
- Dose: 20=9650 mg/day
Venlafaxine
- Dose: 37.5=96225 mg/day =

Topical Analgesics

5% lidocaine patch=20
- First choice for postherpetic neuralgia =
- Wear patch for 12 consecutive hours over the = area of=20 pain, then discard; apply a new patch 12 hr later
EMLA (lidocaine 2.5% and prilocaine = 2.5%)=20
- Effective in children for needle insertions, = blood=20 draws, etc.

Selective Cyclooxygenase-2 Inhibitor =

Celecoxib=20
- Helpful for some patients, particularly = those at low=20 risk for coronary artery disease or cerebrovascular disease
- Dose: 100=96200 mg b.i.d. =

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Best References

Portenoy RK, et al: Lancet 353:1695, 1999 [PMID=20 10335806]

SUPPORT Principal Investigators: JAMA 274:1591, = 1995 [PMID=20 7474243]

Zech DF, et al: Pain 63:65, 1995 [PMID = 8577492]

The author is a member of the speakers' = bureaus of=20 Pfizer/Pharmacia, GlaxoSmithKline, and Ortho-McNeil Pharmaceutical,=20 Inc.

April=20 2006