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Guidelines for the Use of Antiretroviral
Agents in Pediatric HIV Infection
Managing Complications of HIV Infection in
HIV-Infected Children on Antiretroviral Therapy
Pain Management
March 2005
About This Presentation
These slides were developed using the March 2005 Pediatric
Guidelines. The intended audience is clinicians involved in the care
of patients with HIV.
The user is cautioned that, due to the rapidly changing field of HIV
care, this information could become out of date quickly. Finally, it is
intended that these slides be used as prepared, without changes in
either content or attribution. Users are asked to honor this intent.
-AETC NRC
http://www.aids-etc.org
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Introduction
 Pain is multifactorial, biologically complex
 Associated with decreased quality of life,
increased mortality, lower CD4%
 Common, particularly in younger children and
girls
 Sources: many, including nerve or muscle
inflammation, cardiomyopathy, drug toxicities,
invasive secondary infections
 Stressors may amplify pain
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Assessment
 Self-report
 Pediatric visual analogue pain scales and rating
systems, modified for age, developmental
status, severity of illness, cultural factors
 Observational and behavioral assessment
 Functional performance
 General Health Assessment for Children
 Functional Status II (R)
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Principles of Pain Management
 Diagnose and treat underlying medical
conditions
 Involve the child and caretakers in
developing strategies
 Consider consultation with pediatric pain
specialist
 Combine nonpharmacologic and
pharmacologic therapies
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Nonpharmacologic Interventions
 Relaxation techniques, behavior modifications
 Environmental management (play, music,
scheduled medical/nursing interventions, structured
sleep and rest times)
 Gentle handling, supportive positioning
 Nutritional support, hydration, electrolyte
replacement
 Optimized tissue perfusion and oxygenation
 Transcutaneous electrical stimulation (TENS),
massage, whirlpool, physical therapy
 Acupuncture
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Pharmacologic Treatment
 Dosing guidelines should be consulted, but
dosages must be individualized
 Effective pediatric analgesic dosage may not be
identified (eg, tricyclics, SSRIs, and
anticonvulsant medications)
 For adjunctive analgesics, analgesic dosage
may be lower than the standard dosage for a
medication’s primary indication
 Start at low dosages, increase as necessary and
as tolerated
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Pharmacologic Treatment
 Many analgesics undergo hepatic
metabolism
 May have interactions with PIs or NNRTIs
 Analgesic and/or ARV drug levels may be
altered
 Risk of analgesic toxicity or withdrawal; suboptimal or
toxic PI or NNRTI concentrations
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Types of Medications
Drug Category
Representative
Medications
Comments
GABA agonists
Baclofen, midazolam,
lorazepam, diazepam
Baclofen is often used for muscle spasms; stimulates
GABA-B receptors, inhibiting the release of the
excitatory amino acids glutamate and aspartate.
Mu opioid
agonists
Fentanyl, morphine
Respiratory monitoring required. Transdermal
fentanyl should not be used for episodic pain, as it
has a slow onset, long duration.
NMDA receptor
antagonists
Dextromethorphan,
ketamine
Dextromethorphan may cause ataxia, dizziness.
Ketamine may increase heart rate, blood pressure,
cardiac output, and intracranial and intraocular
pressure; also may cause hallucinations.
Mixed agonists
Methadone (mu opioid
and NMDA effects);
tramadol (mu opioid
and norepinephrine,
serotonin effects)
Methadone is available in liquid form for young
children. Marked variability in clearance requires
close monitoring to avoid excessive sedation.
Pediatric dosage, safety, and duration of
administration have yet to be determined for
tramadol.
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Types of Medications
Drug Category
Representative
Medications
Comments
Alpha2 adrenergic
agonist
Clonidine
Modulates sympathetic responses. Opioid-sparing effect.
Transdermal dosing available. Discontinue if patient is
hypotensive, septic, or depressed.
Tricyclic
antidepressants
Amitriptyline,
nortriptyline
Blocks NMDA receptors. Releases endogenous opioids.
Clearance is variable. Additional benefit with second
(a.m.) dose. Plasma concentrations may guide high doses.
SSRIs
Paroxetine, sertraline,
fluoxetine
Mechanism of antinociceptive effect unknown; may
involve both central opioid and serotoninergic pathways.
Anticonvulsants
with analgesic
effect
Gabapentin,
lamotrigine,
topiramate
Gabapentin modulates calcium channels, increases GABA
synthesis, reduces glutamate. Used in treatment of
neuropathic pain. Topiramate: monitor for drug
interactions with ARVs.
NSAIDs
Ibuprofen, celecoxib,
diclofenac,
acetaminophen,
ketorolac
Inhibits cyclooxygenase-2 (COX-2). Few class
differences. Ketorolac is the primary parenteral NSAID,
but may cause hepatic dysfunction and GI bleeding.
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Special Considerations
Opioids
 For moderate to severe pain
 Excellent analgesia; generally safe
 Concurrent use with other agents may
enhance analgesia:
 GABA agonists, alpha2 agonists, TCAs,
SSRIs, anticonvulsants
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Special Considerations
Opioid complications:
 Excessive sedation
 Consider low-dose a.m. stimulants
(dextroamphetamine, methylphenidate)
 Itching and constipation
 Consider very small doses of naloxone
 Switch narcotic (eg, to methadone)
 Nausea and vomiting
 Change narcotic
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Special Considerations
Methadone
 Has NMDA receptor antagonism
 Recommended for long-term treatment of
neuropathic pain refractory to nonnarcotics
 May induce less tolerance than other narcotics
 In adults, may be associated with lower CD4%
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Special Considerations
Methadone
Switching to methadone from high-dose morphine,
Dilaudid, fentanyl
 Incomplete cross-tolerance to methadone
 Start at LOW dosage (20% of expected
equipotent dosage)
 Risk of respiratory depression at full equipotent
dosage
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Special Considerations
Methadone
 Some PIs (eg, lopinavir) and NNRTIs (efavirenz,
nevirapine) induce metabolism of methadone,
lower serum drug levels
 Opioid withdrawal symptoms may occur
 Higher methadone doses may be needed
 Risk of methadone toxicity if interacting ARVs
are discontinued
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Special Considerations
Weaning from long-term opioid and
benzodiazepine therapy
 Minimize physiological stress
 Use clonidine (alpha2 agonist), transdermal or
oral, to reduce withdrawal symptoms
 Transition from IV narcotics to methadone (or
fentanyl patch, morphine, MS Contin)
 Transition from midazolam to lorazepam
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Special Considerations
Weaning from long-term opioid and
benzodiazepine therapy
 Wean methadone 5-10% every 2-3 days, as
tolerated, alternating with 5-10% wean of
lorazepam
 Wean clonidine at least 3-5 days after
discontinuation of narcotics
 Assess frequently for withdrawal symptoms
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Special Considerations
Escalating narcotic and sedative
requirements
 Initiate alpha2 agonist and NMDA receptor
antagonist
 Consider clonidine, dextromethorphan (lowdose)
 Substitute methadone for other narcotics,
lorazepam for midazolam
 Consider rotating narcotics
 Consider regional anesthesia for localized pain
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Special Considerations
 Analgesia and sedation for painful
procedures
 For venipuncture: nonpharmacologic interventions
plus topical and local anesthesia
 For more invasive procedures, consider conscious
sedation
 Caution with midazolam: levels increased by some PIs and
NNRTIs
 Caution with fentanyl: respiratory and cardiac depression
with loading doses in some patients on PIs or NNRTIs
 Start at low dosages, titrate carefully, monitor closely
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Special Considerations
 Peripheral neuropathy
 Appears to be less severe in children
 Lidoderm patch, with other analgesics as needed
 Discontinue precipitating medications, if possible
 Neuropathic pain
 Persists or intensifies independent of ongoing tissue
injury or inflammation
 May need combination therapy (nonnarcotics with or
without narcotics)
 Consult pain specialist
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Special Considerations
 Movement disorders
 Consider levodopa
 Consult with neurology, anesthesia, and
rehabilitation specialists
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Treatment of Specific Pain
Syndromes
Indication
Goals of Treatment
Pharmacologic Approach
Localized or regional pain
due to tissue damage,
inflammation, invasive
infection, tumor
Decrease inflammation
and limit tissue damage;
interrupt pain
transmission; analgesia
Topical analgesics; local
anesthetics; capsaicin; topical
steroids; NSAIDs; opioids; regional
anesthesia
Myopathic process
Resolve underlying
process; decrease
inflammation
Stop offending medications;
maximize ARV therapy; NSAIDs;
consider systemic steroids
Systemic inflammatory
process
Decrease inflammation
and stress
NSAIDs; consider corticosteroids
Peripheral neuropathy
Limit inflammation and
progression
Lidoderm patch; tricyclic or SSRI;
anticonvulsant; alpha2 agonist; stop
offending medications
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Treatment of Specific Pain
Syndromes
Indication
Goals of Treatment
Pharmacologic Approach
Neuropathic pain
syndromes
Modulation of CNS
excitatory an sympathetic
responses; decrease stress
analgesia; mobilization
Tricyclic or SSRI; alpha2 agonist;
NSAID; anticonvulsant; opioid
with NMDA blocking effect;
NMDA receptor antagonist;
systemic lidocaine; regional
anesthesia
Movement disorder with
rigidity, spasticity
Improve comfort and
mobility
GABA agonist; L-dopa; regional
anesthesia
Encephalopathic process Improve sleep; decrease
with irritability, insomnia CNS inflammation
GABA agonist; ARV; NMDA
receptor antagonist;
anticonvulsant
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Treatment of Specific Pain
Syndromes
Indication
Goals of Treatment
Pharmacologic Approach
Respiratory distress or
severe congestive heart
failure
Sedation and/or analgesia
for comfort and to help
tolerate interventions
O2; morphine and other
opioids; GABA agonist
Escalating narcotic and
anesthetic resistance
Blunt excalation; preserve
opioid responsiveness
Alpha2 agonist; opioid with
NMDA blocking effect;
NMDA receptor antagonist
Opioid or GABA agonist Minimize stress responses;
wean at tolerable rate
withdrawal
Alpha2 agonist; opioid with
NMDA blocking effect, longacting GABA agonist
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Conclusion
 Pain may significantly diminish quality of
life and complicate medical management
 Optimal management often requires
multidisciplinary collaboration
(anesthesia, pain service, nursing, social
services, others)
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