Pain management in the hospital
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Pain Management in the Hospital. Rog Kyle, MD Medical University of South Carolina 2/7/12. Objectives. Differentiate acute, chronic, somatic, neuropathic, referred, and visceral pain syndromes. Differentiate tolerance, dependence, addiction, and pseudo-addiction.

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Pain management in the hospital

Pain Management in the Hospital

Rog Kyle, MD

Medical University of South Carolina

2/7/12


Objectives

Objectives

  • Differentiate acute, chronic, somatic, neuropathic, referred, and visceral pain syndromes.

  • Differentiate tolerance, dependence, addiction, and pseudo-addiction.

  • Explain the indications and limitations of non-pharmacological, pharmacological, and adjuvant methods of pain control in the hospitalized patient.

  • Explain the indications and limitations of opioid pharmacotherapy.

  • Determine equianalgesic dosing for pharmacologic therapy as needed.


Key messages

Key Messages

  • Chronic pain is a significant problem in the elderly

  • There are many different mechanisms involved in generation and perception of pain

  • Both non-opioid and opioid options are available for managing pain.

  • Different classes of medication and non-pharmacotherapies are available for the management of pain syndromes

  • Opioids have a narrow therapeutic window and their use must be weighed carefully in the management of chronic, non-cancer pain


Pain management in the hospital

  • Types of pain

  • Tolerance, dependence and addiction

  • Medications


Types of pain

Types of Pain


Nociceptive pain

Nociceptive Pain

  • Nociceptors = pain fiber sensitive to noxious stimuli

  • Somatic – injury to tissues, well localized

  • Visceral – injury to organs (stretch receptors), poorly localized

  • Referred – afferent visceral fibers + somatic to same spinothalamic pathway


Neuropathic pain

Neuropathic pain

  • Abnormal neural activity secondary to disease, injury, or dysfunction

  • Persists without ongoing injury (trigeminal neuralgia, DM neuropathy)

  • Types:

    • Sympathetic – from peripheral nerve injury with autonomic changes

      • “New” term – Complex Regional Pain Syndrome (CRPS)

        • Type I = RSD

        • Type II = causalgia

    • Peripheral autonomic pain –

      • Same but without autonomic change (PHN)

    • Central Pain (spinal cord injury)


Pain management in the hospital

Tolerance, Dependence, Addiction


Tolerance

Tolerance

  • Tolerance - increase the dose to maintain equipotent analgesic effects

    • Associative - linked to environmental clues and involves psychological factors

    • Adaptive - involves down-regulation or desensitization of opioid receptors, or both


Tolerance1

Tolerance

  • Repeated administration of opioids

    • Desensitization or down-regulation

    • Sensitization – similar to neuropathic pain with increased sensitivity to pain


Pain management in the hospital

  • Can’t distinguish the hyperalgesia due to opioid treatment from the hyperalgesia due to worsening neuropathic pain

  • It is often impossible to distinguish between pharmacologic tolerance and abnormal pain sensitivity

    • Both lead to escalation of opioid therapy that ultimately fails


Dependence

Dependence

  • Rapid discontinuation of opioid following prolonged administration produces symptoms

    • Dysphoria

    • Anxiety

    • Mood volatility

    • Hypertension

    • Tachycardia

    • Sweating


Dependence1

Dependence

  • Psychological dependence

    • Extreme behavior (craving) associated with procuring/consuming drug

    • High vs. withdrawal

  • Physical dependence

    • class-specific withdrawal syndrome that can be produced by abrupt cessation or rapid dose reduction of a drug (or administration of an antagonist)


Addiction

Addiction

  • Physical and psychological dependence

  • Chronic relapsing disorder characterized by persistent drug-seeking and drug-taking behaviors

  • Impaired control over use, compulsive use, continued use despite harm and craving


Medications

Medications


Nsaids

NSAIDS


Wide variety

Wide variety

  • 60 million Rx’s/yr

  • Clinical efficacy of equipotent doses is similar

  • Individual responses highly variable – especially toxicity

    • cox-1 vs. cox-2

    • naprosyn may have greatest relative cardiovascular safety profile

    • diclofenac - available as a topical patch for pain due to trauma and as a gel for treatment of painful joints

    • sulindac – increased hepatotoxicity

    • indomethacin - GI and central nervous system adverse effects may be more frequent or severe than with other NSAIDs

    • ketorolac - risk of gastropathy is increased when use exceeds five days

    • piroxicam – high GI toxicity

    • celecoxib – no antiplatelet function. Increased CV risk above 200mg/day


Utility of nsaids

Utility of NSAIDS

  • Variations in patient response

  • Generally indicated in mild to moderate pain

  • Mostly for pain of somatic origin although has a CNS effect as well

  • Each trial should last a couple weeks

  • May have an opioid sparing effect as adjunct

  • Use at the maximum anti-inflammatory dose

  • Protein bound – may interfere with other protein bound drugs (dilantin. coumadin)


Utility of nsaids1

Utility of NSAIDS

  • Noted variability in the response to NSAIDS between patients

    • Does not appear related to serum concentrations

    • Degree of Cox inhibition doesn’t correlate with effect

    • Non-prostaglandin effects may predominate in some patients

    • Switching between classes of NSAIDS may be beneficial


Tricyclic antidepressants

Tricyclic Antidepressants


Utility in pain management

Utility in pain management

  • Most useful in neuropathic pain

  • None of the TCA’s carries an indication for pain management

  • Used frequently in variety of settings

  • Amitriptyline most widely studied

  • Anti-depressant effects may alleviate depression associated with chronic pain

  • May have synergy with opioids

  • Switching TCA’s based on effect and/or side effects can be tried…but often frustrating


Mechanism of action

Mechanism of action

  • Generally unknown

  • Theories involve action on serotonin, norepinephrine receptors (TCAs with the greatest effect upon serotonin seem to have the greatest analgesic effect)

  • May potentiate endogenous opioid system

  • However, potent serotonin RI’s have no analgesic effect of their own

  • Can take weeks to work


Side effects

Side effects

  • Anticholinergic (amitriptyline > nortriptyline)

  • Also GI, CV, neurologic (esp. sedation – maybe a +’ve)

  • Anticholinergic and CNS effects may diminish in days to weeks – “ride it out”


Anticonvulsants

Anticonvulsants


Utility in pain management1

Utility in pain management

  • Can be very effective, particularly in neuropathic pain

  • Wide variation in use among pain specialists, except with carbamazepine for trigeminal neuralgia

  • Gabapentin is frequently a first choice as levels do not need monitoring


Mechanism of action1

Mechanism of action

  • Theories include membrane stabilization (phenytoin), inhibition of repeated neuronal discharges (carbamazepine), GABA inhibition enhancement (valproic acid, clonazepam), GABA mimetics (gabapentin, pregabalin).


Adjuvant medications

Adjuvant medications


Benzodiazepines

Benzodiazepines

  • Good choice when anxiety complicates pain management (esp’ly cancer patients)

  • Clonazepam particularly useful in neuropathic pain (GABA potentiation)

  • Drawbacks well known

    • Addictive potential is significant

    • Potentiates sedation and respiratory depression


Antispasmodics

Antispasmodics

  • Painful muscle spasm, myoclonic jerks can accompany a variety of pain conditions (and opioids)

    • toxicity of morphine

  • Mechanism of action may reflect their sedative effects more than direct muscle effect

  • Commonly used – cyclopenzaprine, carisoprodol, baclofen, methcarbamol


Ssri snri

SSRI/SNRI

  • Often tried when TCA side effects limit utility

  • May be treating depression – not an uncommon consequence of life with chronic pain

  • Venlafaxine has been shown to be similar to imipramine in one study of painful neuropathy

  • Duloxetine approved for diabetic peripheral neuropathy

  • Depression is probably undertreated in chronic pain patients in general (cancer and non-cancer pts)


Opioids

Opioids


Opioids1

Opioids

  • Role in treatment of pain is well established for acute pain, malignant pain and care of the terminally ill

  • Role in chronic non-cancer pain is more controversial

  • WHO Ladder


Opioids2

Opioids

  • WHO Ladder

  • Moderate to severe - fixed dose schedule and not on a “prn” basis

  • Stepwise approach

  • Adjuvants useful in enhancing analgesia and controlling side effects


Opioids3

Opioids

  • Equi-analgesic dosing


Pain management in the hospital

http://www.musc.edu/pharmacyservices/medusepol/OpioidAnalgesicConversionChart.pdf


Opioids4

Opioids

  • Equianalgesic dosing

  • Equianalgesic conversion

    • MUSC pharmacy recommends 50% dose reduction for cross tolerance (others recommend 25-50%) except for methadone and fentanyl (see below)


Pain management in the hospital

http://www.musc.edu/pharmacyservices/medusepol/OpioidAnalgesicConversionChart.pdf


Opioids5

Opioids

  • Equianalgesic dosing

  • Equianalgesic conversion

  • Methadone conversion ratio


Pain management in the hospital

http://www.musc.edu/pharmacyservices/medusepol/OpioidAnalgesicConversionChart.pdf


Opioids6

Opioids

  • Equianalgesic dosing

  • Equianalgesic conversion

  • Methadone conversion ratio

  • Fentanyl conversion


Pain management in the hospital

http://www.musc.edu/pharmacyservices/medusepol/OpioidAnalgesicConversionChart.pdf


Therapeutic failures and adverse outcomes

Therapeutic failures and adverse outcomes

  • One of the fundamental principles of pain management is that the dose of an opioid should be increased until maximal analgesia is achieved with minimal side effects

  • What to do when this doesn’t work?

  • Identifying causes of treatment failure

    • Progression of underlying illness

    • Pharmacologic tolerance

    • Increased pain sensitivity


Pain management in the hospital

PCA

  • Efficacy established in post-op pain

  • Morphine, hydromorphone, fentanyl

    • Higher pt satisfaction, better pain control, higher amount of opioid overall


Pain management in the hospital

PCA

  • Morphine

    • Metabolites (morphine-6-glucuronide) accumulate in renal failure = sedation, respiratory depression

  • Fentanyl

    • Less histamine release = better in hypotension, bronchospasm

    • Inactive metabolites (hepatic), Safe in ESRD

  • Hydromorphone

    • Safe in ESRD

    • High concentration/low volume


Pca conversion

PCA Conversion

  • When converting from a PCA to an oral regimen in patients requiring long term pain control

    • Give approximately 50% of 24 hr total opioid use as a long acting oral formulation and 50% as breakthrough oral formulation

    • Reduce dose 25-50% to account for cross tolerance if switching opioid


Side effects1

Side Effects

  • Depressed respiratory drive

  • Depressed consciousness, hallucinations

  • Hypotension

  • Nausea, vomiting

  • Ileus, constipation

  • Urinary retention


Examples equianalgesic dosing

Examples – Equianalgesic Dosing

  • Convert a patient requiring 120 mg of p.o. morphine and 20 mg i.v. morphine to p.o. oxycodone

    • 20 mg i.v. morphine = 60 mg p.o. morphine

    • 120 mg + 60 mg = 180 mg morphine/24 hr

    • Ratio 3:2 for morphine:oxycodone (po) = 120 mg oxycodone

    • Reduce by 25-50% = 10-15 mg oxycodone po Q4H


Examples methadone conversion

Examples – Methadone Conversion

  • Convert a patient taking 300 mg MS Contin BID and 60 mg MSIR Q4H to methadone

    • Total oral morphine/24 hrs = 960mg

    • Conversion ratio is 16 for 960 mg = 960/16 = 60

    • Reduce by 50% for cross tolerance = 30

    • Given Q8H = 30/3 = 10 mg Q8H methadone


Examples pca to oral opioid

Examples – PCA to Oral Opioid

  • Convert a patient with hydromorphone PCA set at basal rate of 1 mg/hr and breakthrough of 0.2mg Q10 min that utilized a total of 6 mg of breakthrough in previous 12 hours to oral oxycodone

    • 24 hr iv hydromorphone use = 24 mg basal (1 mg/hr x 24 hrs) + 12 mg breakthrough (6 mg/12 hrs x 2) = 36 mg hydromorphone IV

    • oxycodone:hydromorphone iv = 20:1.5 = 480 mg oxycodone

    • Reduce 50% for cross tolerance = 240 mg oxycodone

    • Giving 50% of total as long acting = OxyContin 60 mg BID + 20 mg oxycodone Q4H


References

References

  • Ballantyne JC, Mao J. Opioid Therapy for Chronic Pain. N Engl J Med 2003;349:1943-53.

  • Hudcova J, McNicol ED, Quah CS, Lau J, Carr DB. Patient controlled opioid analgesia versus conventional opioid analgesia for postoperative pain (Review). Cochrane Database of Systematic Reviews 2006, Issue 4. Art. No.: CD003348

  • Roelofs PD, Deyo RA, Koes BW, Scholten RJ, van Tulder MW. Nonsteroidal anti-inflammatory drugs for low back pain: an updated Cochrane review. Spine (Phila Pa 1976). 2008;33(16):1766

  • Von Korff M, Kolodny A, Deyo RA, Chou R. Long-term opioid therapy reconsidered. Ann Intern Med. 2011;155(5):325

  • Joranson DE, Ryan KM, Gilson AM, Dahl JL. Trends in medical use and abuse of opioid analgesics. JAMA. 2000;283(13):1710

  • Dobecki DA, Schocket SM, Wallace MS. Update on pharmacotherapy guidelines for the treatment of neuropathic pain. Curr Pain Headache Rep. 2006;10(3):185

  • Saarto T, Wiffen PJ. Antidepressants for neuropathic pain: a Cochrane review. J Neurol Neurosurg Psychiatry. 2010;81(12):1372


References1

References

  • Ballantyne JC, Mao J. Opioid Therapy for Chronic Pain. N Engl J Med 2003;349:1943-53.

  • Hudcova J, McNicol ED, Quah CS, Lau J, Carr DB. Patient controlled opioid analgesia versus conventional opioid analgesia for postoperative pain (Review). Cochrane Database of Systematic Reviews 2006, Issue 4. Art. No.: CD003348

  • Roelofs PD, Deyo RA, Koes BW, Scholten RJ, van Tulder MW. Nonsteroidal anti-inflammatory drugs for low back pain: an updated Cochrane review. Spine (Phila Pa 1976). 2008;33(16):1766

  • Von Korff M, Kolodny A, Deyo RA, Chou R. Long-term opioid therapy reconsidered. Ann Intern Med. 2011;155(5):325

  • Joranson DE, Ryan KM, Gilson AM, Dahl JL. Trends in medical use and abuse of opioid analgesics. JAMA. 2000;283(13):1710

  • Dobecki DA, Schocket SM, Wallace MS. Update on pharmacotherapy guidelines for the treatment of neuropathic pain. Curr Pain Headache Rep. 2006;10(3):185

  • Saarto T, Wiffen PJ. Antidepressants for neuropathic pain: a Cochrane review. J Neurol Neurosurg Psychiatry. 2010;81(12):1372


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