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 pseudoaddiction.
• Explain the indications and limitations of nonpharmacological, 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
• 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
• Types of pain
• Tolerance, dependence and addiction
• Medications
Types of 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
• 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)
Tolerance, Dependence, Addiction
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
Tolerance
• Repeated administration of opioids
– Desensitization or down-regulation
– Sensitization – similar to neuropathic pain with
increased sensitivity to pain
• 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
• Rapid discontinuation of opioid following
prolonged administration produces symptoms
– Dysphoria
– Anxiety
– Mood volatility
– Hypertension
– Tachycardia
– Sweating
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
• 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
NSAIDS
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
• 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 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
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
• 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
• 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
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 action
• Theories include membrane stabilization
(phenytoin), inhibition of repeated neuronal
discharges (carbamazepine), GABA inhibition
enhancement (valproic acid, clonazepam),
GABA mimetics (gabapentin, pregabalin).
Adjuvant medications
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
• 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
• 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
• 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
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
Opioids
• Equi-analgesic dosing
http://www.musc.edu/pharmacyservices/medusepol/OpioidAnalgesicConversionChart.pdf
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)
http://www.musc.edu/pharmacyservices/medusepol/OpioidAnalgesicConversionChart.pdf
Opioids
• Equianalgesic dosing
• Equianalgesic conversion
• Methadone conversion ratio
http://www.musc.edu/pharmacyservices/medusepol/OpioidAnalgesicConversionChart.pdf
Opioids
•
•
•
•
Equianalgesic dosing
Equianalgesic conversion
Methadone conversion ratio
Fentanyl conversion
http://www.musc.edu/pharmacyservices/medusepol/OpioidAnalgesicConversionChart.pdf
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
PCA
• Efficacy established in post-op pain
• Morphine, hydromorphone, fentanyl
– Higher pt satisfaction, better pain control, higher
amount of opioid overall
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
• 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 Effects
•
•
•
•
•
•
Depressed respiratory drive
Depressed consciousness, hallucinations
Hypotension
Nausea, vomiting
Ileus, constipation
Urinary retention
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
• 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
• 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
1.
2.
3.
4.
5.
6.
7.
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 antiinflammatory 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
References
1.
2.
3.
4.
5.
6.
7.
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 antiinflammatory 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