# Presentation: 013072

## Pediatric Analgesic Use

- Debra L. Friedman MD
- Seattle Cancer Care Alliance

## Utilization

- Thoughts and beliefs
- Availability of agents
- Supportive Care
- Clinical setting

## Administration	

- Preparations
- Route
- Dose
- Conflicting health issues
- Other external issues

## Evaluation

- Who evaluates the pain management?
- What is evaluated?
- Where is the pain management evaluated?
- When is the pain management evaluated?

## Patient and Family Concerns

- Physicians thought and beliefs
- Belief in child’s pain
- Pain is scary and unsettling
- Listen to parents and children
- Consult with other experts
- Children are not little adults

## Patient and Family Concerns

- Provide communication, education
- Initiate use of analgesics early
- Do not fear addiction
- Give parents and children respect and appreciate their areas of expertise, capability and strength
- Involve children and family in decisions

## Standards and Policies

- Joint Commission on Accreditation of Healthcare Organizations
- World Health Organization
- American Academy of Pediatrics
- Agency for Health Care Policy  and Research
- Federal Drug Administration
- American Pain Society
- American Academy of Pain Medicine
- American Society of Addiction Medicine

## What is pain?

- Pain is an unpleasant, sensory and emotional experience, associated with actual or potential tissue damage, or described in terms of such damage.
- 	International Association for the Study of Pain

## Pain Assessment in Children

- Address the various components and match the intervention to the individual situation
- Affective
- Behavioral
- Cognitive
- Sensory
- Physiological

## Routes of Analgesic Administration in Children

- Oral
- Taste
- Preparation
- Onset of action
- Bioavailability
- Other physiologic conditions
- Intramuscular Painful administration
- Wide fluctuations in absorption from muscle
- Intravenous: continuous or intermittent
- Safety
- Comfort
- Doses and special dilutions

## Routes of Analgesic Administration in Children

- Transmucosal
- Issues of safety
- Confusion with candy
- Appropriate monitoring and dosing
- Subcutaneous continuous infusions
- Rarely used due to need for local anesthetic
- Transdermal
- Delay until full onset of action
- Ability to dose appropriately in young children
- Other physiologic conditions
- Regional analgesia
- Used in young infants or children with chronic lung disease

## Dosing issues in children

- Children are not little adults
- Dosing should not be guided by fears of addiction
- Use of established guidelines as a starting point
- Escalate doses with goal of comfort with tolerable side effects
- Pharmacokinetics

## Agents to treat mild pain

- Acetaminophen
- Ibuprofen
- Choline Magnesium Salicylate
- Naproxen

## Agents to treat moderate pain

- Codeine, hydrocodone, oxycodone
- 			 +/-acetaminophen
- Ketorolac

## Agents to treat severe pain

- Morphine
- Hydromorphone
- Fentanyl
- Methadone

## Adjunctive medications

- Antipyretics
- Anxiolytics
- Sedatives
- Antipruritics
- Antiemetics
- Antidepressants
- Anticonvulsants
- Antispasmodics

## Levels of treatment intensity

## Opioid Pharmacokinetics

- Morphine
- First-pass metabolism results in poor and unpredictable bioavailability from oral dosing
- 30% plasma protein-bound
- Detoxification by glucuronidation in liver
- Prolonged clearance and lower clearance rates in infants
- Half-life decreases with increasing age
- High inter-individual variability

## Opioid Pharmacokinetics

- Codeine
- 70% bioavailability from oral dosing
- 25% plasma protein-bound
- Metabolized to morphine (10%) and norcodeine
- Excreted in urine as inactive forms
- Half-life 2.5-2.5 hours

## Opioid Pharmacokinetics

- Fentanyl
- Highly lipophilic, redistributes into muscle/fat
- 80 - 85% plasma protein-bound
- 90% metabolized in the liver to inactive metabolites
- Half-life much shorter in infants and young children with higher clearance

## Opioid Pharmacokinetics

- Methadone
- Highly lipophilic, redistributes into muscle/fat
- 80 - 85% plasma protein-bound
- 90% metabolized in the liver  and eliminated in the urine (<10% unchanged)
- Half-life shorter in children than adults

## Common Uses of Opioids in Children

- Mechanically ventilated neonates, infants and children
- Procedural pain
- Acute trauma or illness, including surgery
- Sickle cell anemia vasooclusive crises
- Burns
- Cancer pain

## Intensive Care Unit

- Fentanyl may increase ICP and increase chest wall rigidity
- Morphine may cause some venodilatation
- Concerns over respiratory depression may limit dosing
- Altered hepatic or renal function
- Pain may be more difficult to assess or time may not be taken to assess pain management
- Tobias et al. Ped Clin N Amer 41:1269-1292,1994
- Chambliss et al. Curr Opin Pediatr	9:246-253, 1997
- Jacob et al. J Pain Symptom Manage 20:59-67

## Emergency Department

- Comparison of pediatric and adult centers
- Doctors are less likely to order analgesics for children
- Children are less likely to receive analgesics, even when ordered
- Children more likely to receive non-narcotic agents
- Administration of analgesics are delayed, under-dosed
- Home medications and instructions are inadequate
- Adverse effects of procedural analgesia with appropriate monitoring is rare
- Friedland et al. Ped Emerg Care 13:103-106, 1997
- Pena et al. Ann Emerg Med 34:483-491, 1999
- Bernardo et al. J Trauma Nurs 4:13-21, 1999
- Schechter et al. Pediatrics 77:11-15, 1986
- Selbst et al. Ann Emerg Med 19:1010-1013, 1990
- Hauswald et al. Pediatr Emerg Care 13:263, 1996
- Jacob et al. J Pain Symptom Manage 20:59-67, 2000

## Sickle Cell crises

- Combinations of opioids and non-steroidal agents
- Infusional continuous and bolus infusions
- Avoidance of meperidine
- Need transition from infusional to oral or transdermal
- Delay in starting analgesics
- Need for observational units
- Confusion between tolerance, physical dependence and addiction
- American Pain Society 1999
- Yaster et al. Pediatr Clin N Amer 47:69-710, 2000
- Bohan. Emerg Clin N Amer 19:233-238, 2001
- Shapiro. J Pain Symptom Manage 14:168-174, 1997
- Shapiro. Pain 61:139-144, 1995
- Jacob et al. J Pain Symptom Manage 20:59-67

## Cancer Pain

- Pain may be chronic and may require combinations of agent types and administrations
- Many sets of guidelines exist, but uniformity within and among centers  is lacking
- Under-medication is a common issue, especially towards end of life
- Physiologic conditions dictate choice of agent, mode of administration and dosing
- Need transition from hospital to home setting
- Zeltzer et al., Berde et al., Pediatrics 86:818-831, 1990
- Tyc et al. J Pediatr Oncol Nurs 15:207-215, 1998
- Collins et al. J Pediatr 126:653-657, 1995
- Galloway et al. Pediatr Clin N Amer 47:711-746, 2000
- World health Organization 1996, 1998
- American Pain Society 1999
- Jacob et al. J Pain Symptom Manage 20:59-67

## Research Directions

- Congressional provision declares this decade as the “Decade of Pain Control and Research”
- National Pain Care Policy Act of 2001
- White House conference on pain care
- National center within NIH
- Funding for education/training through the Agency for Health Care research and Quality
- Pain care standards for Medicare + Choice plans
- Annual report on Medicare expenditures
- Pain medicine to be treated as physician specialty

## Focus for Pediatric Research

- Epidemiology and utilization practices
- Pharmacokinetics and pharmacodynamics
- Mechanisms of action
- All new agents should have pediatric trials
- Older agents need pediatric trials
- Broader dosage forms and routes of administration
- Adequate supply of drugs
- Combinations of different drug classes
- Combinations of pharmacologic and non-pharmacologic pain management
- De-stigmatize patients, families and doctors

## Education and Research

- Health care providers
- Children and adolescents
- Parents
- The greater community

- Pharmaceutical industry
- Federal Drug Administration
- National Institutes of Health
- Other granting agencies