March 2005

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

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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The user is cautioned that, due to the rapidly changing field of HIV care, this information could become out of date quickly.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 MedicationsDrug Category Representative

MedicationsComments

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 MedicationsDrug Category Representative

MedicationsComments

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

MethadoneSwitching 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 ConsiderationsWeaning 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 (low-dose) 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 with irritability, insomnia

Improve sleep; decrease 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 withdrawal

Minimize stress responses; wean at tolerable rate

Alpha2 agonist; opioid with NMDA blocking effect, long-acting 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)