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Cancer Pain in Children. 13 th Annual Palliative Care Seminar Hector Rodriguez-Cortes, MD Pediatric Hematologist and Oncologist Pediatric Palliative Care and Hospice. Objectives:. Epidemiology of cancer pain Identify the three different pain categories
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Cancer Pain in Children 13th Annual Palliative Care Seminar Hector Rodriguez-Cortes, MD Pediatric Hematologist and Oncologist Pediatric Palliative Care and Hospice
Objectives: • Epidemiology of cancer pain • Identify the three different pain categories • Identify Treatment and Tumor-Related pain syndromes • Review the Two-step strategy of the WHO guideline
Introduction • Cancer: • evokes immediate fear for patients and their families • potentially fatal disease • can be associated with pain • Symptoms: • may be interconnected • treatment of one symptom may exacerbate another
FREQUENCY OF CANCER PAIN • Multi-factorial: • type of malignancies • sites of involvement • presence or absence of metastases • Prevalence of moderate/severe pain • increasesduring the late phases of malignancy
EPIDEMIOLOGY OF CANCER PAIN IN CHILDREN • Cancer pain: • tumor-related • treatment-related pattern: surgery, medications • Tumor-related pain: • predominates at diagnosis/ early treatment phase • May persisted for a median of 10 days after initiation of treatment. • Examples of tumor-related pain: • Brain tumors: • headache/ abnormal neurologic signs • Mets w spinal cord compression: back pain
EPIDEMIOLOGY OF CANCER PAIN IN CHILDREN • Treatment-related pain: • mucositis • antineoplastic therapy • postoperative pain • procedure-related pain
Breakthrough pain in Children with Cancer • Freidrichsdorf and Postier (2014) • Breakthrough Pain Questionnaire for Children • 57% of children experienced pain • Pain: major tumor tumor surgery >> tumor/ drug-related • Younger children (7-12 year of age) at higher risk than teenagers • PCA
Reason for Breakthrough pain in Children with CancerFreidrichsdorf and Postier (2014) • disease progression • infection at the tumor site • development of tolerance • drug interactions • decreasing renal function • somatization and psychological distress.
PAIN MECHANISMS: • Experience of pain: • Subjective • can be modulated by developmental, familial, situational, emotional, and other factors. • lack of correlation between the extent of tissue injury and the intensity of pain or suffering.
PAIN MECHANISMS: Terminology • Nociception: • sensationof tissue injury or inflammation • alerts an individual to potential or ongoing injury • prompts the avoidance or limitation of further injury • can be activated by: • chemical, thermal, or mechanical stimuli • lack of it can lead to a variety of medical complications • decubitus ulcers.
Somatic pain: Pathophysiology • noxious stimuli • mechanical, thermal, or chemical • Pain signals are carried to the dorsal horn of the spinal cord by: • A-delta fibers: mechanical/thermal • C fibers: all three stimulus types • The signals ascend in the contralateral spinothalamic and spinoreticular tracts • thalamus
TYPES OF PAIN • Pain can be divided into 3 categories: • Somatic • Visceral • Neuropathic • These categories are not mutually exclusivesince a patient's pain may have multiple etiologies.
Somatic pain • Triggered by potential or real injury to tissues • cutaneous burn or an arthritic joint. • Pain • tender and localized. • constant and sometimes throbbing or aching. • it can be acute or chronic. • Bone metastasis is the most common cause of somatic pain
Visceral pain • Mechanism is not well characterized. • Pain: • Poorly localized • less constant • it can dull, colicky • Often referred to a distant cutaneous site. • diaphragmatic irritation: ipsilateral shoulder • passage of a renal stone • Associated: nausea and diaphoresis. • Noxious stimuli that can trigger visceral pain: • ischemia, inflammation, torsion, traction, distension, or impaction
Neuropathic pain • Causes: • Peripheral or central in etiology • infiltration of neural structures by tumor • fibrosis: radiation • injury: surgery • Described as: • prolonged, severe, burning, or squeezing • It can paroxystic • often associated with focal neurologic deficits • relatively resistance to opioids • Often associated with symptoms and signs of autonomic instability ( i.e.., tachycardia, sweating) • Example: herniated intervertebral disc, phantom limb pain, degenerative neuropathies such as Guillain-Barre syndrome.
Neuropathic pain • Clinical features: • Dysesthesias: • abnormal or unfamiliar unpleasant sensations • Allodynia: • an exaggerated response to otherwise non-noxious stimuli, such as light touch of the skin
Measuring Pain • Pain: • often under-recognized in cancer patients • should be assessed frequently and systematically • Principal barrier to effective pain management: • discrepancy between the patient's and physician's assessments of the pain • Anxiety and depression: • may exacerbate, rather than exaggerate, the pain.
Pain measurement tools • Verbal numerical scale • rating pain from zero for "no pain," to 10 for "the worst imaginable pain" • easily implemented and recorded • 10 cm visual analog scale: • used, with or without intensity descriptors • do not reflect the complexity of the pain experience
Pain measurement tools • Non-communicate pain: • intensity must be evaluated by other means. • nonverbal signs of pain • These include: • hypertension, tachycardia, and diaphoresis • Agitation or confusion • Apathy, inactivity, or irritability in patients with cognitive impairment
Principles for the pharmacological management of pain. • WHO: 1986 • dosing at regular intervals • using the appropriate route of administration • adapting treatment to the individual child • WHO: 2012 • using a two-step strategy
Principles for the pharmacological management of pain. • WHO: 1986 • dosing at regular intervals • steady blood level: reducing peaks and troughs • using the appropriate route of administration • Least invasive route (often chosen by the child) • Transdermal patches: long onset time • adapting treatment to the individual child • Frequently assessment, reassessment and modification
Principles for the pharmacological management of pain. • WHO: 1986 • WHO: 2012: two-step strategy • choice depends on the child’s level of pain. • Mild • Moderate to severe pain
Three-step vs. Two-step approach • Difference: • three-step analgesic ladder: • use of codeine as a weak opioid • treatment of moderate pain • two-step approach: • low doses of strong opioid • Two-step: more effective strategy for persisting pain.
The First Step: mild pain • Recommendations: • Paracetamoland ibuprofen • choice for first step (mild pain) • widely available in child-appropriate dosage forms • oral liquids • relatively inexpensive
ANALGESIC MEDICATIONS: Non-opioids • Acetaminophen: • inhibits prostaglandin synthesis • lacks the sedative effects • minimal anti-inflammatory effect • no side effects such as gastritis and inhibition of platelet • Aspirinand NSAIDs in cancer patients: • risk for bleeding • Aspirin: • irreversible inhibition of platelet
The Second Step: Moderate to Severe pain Recommendations: • Morphine • drug of choice • other strong opioids • intolerable side-effects. • Administeropioidanalgesicsin the first step: • clinical judgement • carefulconsiderations of the disabilitycausedby pain
Strong Opioids • Morphine: • first choice • metabolize in the liver • widely used • It can be administered: • oral, rectal, IV, SQ, epidural, intrathecal, or intraventricular • Starting dose for immediate-release oral morphine • 0.1 mg/kg q4 hours. • Very young infants should receive a reduced dose due delayed clearance
Strong Opioids: • Hydromorphone: • oral, IV, SQ, epidural, and intrathecal • used if there are dose-limiting side effects from morphine. • 5-8 times as potent as morphine. • Fentanyl: • transdermal, oral transmucosal, and IV • 50-100 times more potent than morphine • very rapid onset: high lipid solubility • shorter duration of action after IV administration: • used in patients with dose-limiting side effects: pruritus
Strong Opioids: • Meperidine • no advantages over morphine • major drawback: can cause dysphoria, excitation, and convulsions, particularly in patients with impaired renal clearance • Methadone • synthetic opioid that has a prolonged duration of action • its potency is similar to morphine. • convenient as a long-acting medication in patients who are unable to swallow slow-release morphine tablets
Tramadol • Centrally acting analgesic with opioid effects • Control of moderate to moderately severe pain • Food does not affect its rate of absorption • Dosing: • 17 years of age and over: • Starting dose: 25 mg/day q AM and titrated in 25 mg increments as separate doses every 3 days to reach 100 mg/day (25 mg q.i.d.). • may be increased by 50 mg as tolerated every 3 days to reach 200 mg/day (50 mg q.i.d.). • How supplied: 50 mg tab
Codeine Excluded for pain relief from the two-steps Codeine • “weak” opioid • widely available • previously recommended to control moderate pain. • well-known safety but efficacy problems • genetic variability in biotransformation.
Codeine: • prodrug • enzyme CYP2D6: • converted into its active metabolite morphine. • efficacy depends on the amount of active metabolite. • variable expressions of the enzymes • inter-individual and inter-ethnic differences • Fetus: absent or less than 1% • Children less < 5 year: 25% of the adult values
Excluded medicine for pain relief:Codeine • Poor metabolizers: • vary in ethnic groups from 1% to 30% • ineffectiveness • Rapid metabolizer: • metabolize codeine quickly and extensively • risk of severe opioid toxicity, • high and uncontrolled conversion into morphine.
SYNDROMES OF PEDIATRIC CANCER PAIN • Treatment-Related Syndromes • Tumor-Related Syndromes
Treatment-Related Syndromes:Mucositis • Optimal management is not well established. • S/P BMT: • more intense and prolonged that chemotherapy-related. • Therapy: • topical therapies: sodium bicarbonate, hydrogen peroxide, nystatin, viscous lidocaine, dyclonine, • systemic therapies: opioids and systemic antifungal agents.
Treatment-Related Syndromes:Graft-Versus-Host Disease • May be associated with severe abdominal pain. • GVHD is the next most common cause of pain after an allogeneic BMT • Pain due to GVHD frequently requires the administration of opioids
Treatment-Related Syndromes:Phantom Limb Pain • Common among children after amputation of an extremity • Incidence/severity decrease with time after amputation • Prior treatment with chemo increased the risk after subsequent amputation. • Therapy: • tricyclic anti-depressants • opioids seen to be ineffective • early and frequent use of a limb prosthesis may reduce the duration and severity