Acute and Chronic Pediatric Pain Management Deborah A. Ward, PharmD, BCOP, BCPS
Disclosure Information  Nothing to disclose
Learning Objectives Recognize the barriers encountered in pediatric pain assessment Describe the role of hepatic and renal maturity as it pertains to providing safe and effective drug therapy in a young patient Review drug therapy prescribed in both the acute and chronic setting in the pediatric pain population
Pediatric Pain Assessment
Suffering children hurt us J. Barber Pediatrician 16:119; 1989
Audience Response Question 1  Which of the following has been reported to be the most painful in the pediatric population? A. B. C. D.
Needles Broken Limbs Surgery Trauma
A Vulnerable Population Children continue to be inadequately treated –Others include the elderly and minorities –Lack of comparable randomized controlled trials –Few published meta-analyses or systematic reviews
FDA Drug Testing in children –Mandates for newer agents but what about the rest?
Barriers to Pain Assessment Perception that infants and children do not feel pain and that there is no untoward consequence from untreated pain Lack of assessment/reassessment of pain Lack of knowledge on how to treat pain Feeling that pain management in children is too time-consuming and takes too much effort Fear of adequately using analgesic medicine due to adverse side effects Peds 108(3):793-797;2001
Audience Response Question 2  Which of the following is the most accurate source of pain information in a child? A. B. C. D.
Parents Nursing staff Patient Health care provider
Pediatric Pain Assessment Self-report –The most reliable estimate of pain –Requires verbal and cognitive ability –Visual Analogue Scales • Sensitivity and specificity • Reproducible • > 20 validated for use in infancy • Lack of a gold standard
Pain Intensity Wong-Baker FACES Pain Rating Scale
From Wong DL, Hockenberry-Eaton M, Wilson D, Winkelstein ML, Schwartz P: Wong’s Essentials of Pediatric Nursing, 6/e, St. Louis, 2001, P. 1301. Copyrighted by Mosby, Inc. Reprinted by permission.
Cognitive Development Barriers Inability to quantify perception of pain – Neonates and young children – By age 2 localize pain by pointing – By age 5 can convey severity of pain
Lack of metacognitive skills – Knowledge and control of the process of thinking – Well developed by adolescence
Inability to understand the nature of their pain McGrath, P et al. Clin J of Pain, 1996, 12(2):135-141
Patient Case 1 IR is a 6 month old diagnosed with non-metastatic ATRT (primary of posterior fossa) who was admitted for meningitis – Course of Vancomycin – Dural patch wash, VPS placement
Follow up MRI per protocol demonstrates PD Parents report cry is different from baseline, morphine is now scheduled but parents are concerned for constipation Concurrent therapy includes Levetiracetam, Lorazepam, Dexamethasone, TPN/Lipids/Trophic feeds PCA is initiated, patient comforted in Mom’s arms
Pain Assessment in the Very Young Physiologic Parameters –Nonspecific (ex. heart rate)
Behavioral Scales –NPASS (neonatal pain, agitation, & sedation score) –PIPP (premature infant pain profile) –FLACC (face, leg, activity, cry, consolability) –Applicable to neonates, infants, preverbal/nonverbal children –May underrepresent the intensity of persistent pain
FLACC Scale: Pain Assessment Tool
Developmental Issues in Analgesic Pharmacology
What’s “THE” Pediatric Dose? Drug development provides very limited data in children – “MTD” & safety are poorly defined in Phase I-II – “Pivotal” Phase III studies seldom done for serious pediatric diseases
“Usual Recommended” Pediatric Doses – Often extrapolated from adult data – Do not adequately address Growth & Development and Drug Disposition
Drug Development Process Phase I studies –Determine the dose of a new drug –80% of adult dose as starting point –Endpoint •Determine MTD •Prevent toxicity, NOT determine efficacy
–Under-dosing becomes intrinsic to system
Drug Development Process (cont’d) Dose Level 2 – Recommended for Phase II studies – Tolerable toxicity – Variations in drug handling will result in under-dosing in some patients
Dose Level 3 – Defined as the MTD – Dose-limiting toxicity can result due to impairment of drug handling capabilities
Hitting The Mark Ineffective analgesic effect
Target range
Excess toxicity
Dose level
Courtesy of Dr John Rodman, 2005
Factors Affecting Drug Disposition Physical and chemical characteristics of the drug itself – Molecular size and weight – Lipid and water solubility – Affinity for plasma proteins
Physiologic patient factors – Maturational changes in organ function – Age related changes in body composition
Combination determines response
PK and Pediatric Patients Absorption – Gastric pH, acid secretion, emptying time – Intestinal motility – Pancreatic enzyme activity
Distribution – Body composition • Extracellular and total body water • Fat distribution and lean body mass
– Plasma proteins
PK and Pediatric Patients (cont’d) Metabolism – Phase I reactions • Oxidation, reduction, and methylation • Isoforms of CYP-450 and CYP-450 reductase
– Phase II reactions • Conjugation, sulfation, and acetylation
Renal Elimination – Tubular secretion: developed by 7 months – Blood flow: ↑ with age (↑ CO and ↓ PVR) – GFR: approaches adult values by 5 months
GFR Age
mL/min/1.73m2
Range
Premie
47
29 – 65
2 – 8 days
38
29 – 60
4 – 28 days
48
28 – 68
1 – 5.9 months
77
41 – 103
6 – 11.9 mons
103
49 – 157
Adult
117 – 131
72 – 176
Newborn Physiology Major organ systems are anatomically well developed at birth but functionally delayed – Hepatic enzyme systems • Opioids, acetaminophen, nonsteroidal anti-inflammatory drugs, and amide local anesthetics
– Diminished glomerular filtration rates • Significantly longer half-lives of renally eliminated drugs
Differences in opioid receptor distribution and function Diminished ventilatory responses
NEJM 2002; 347 (14).
Treatment of Acute and Chronic Pediatric Pain
What Are We Treating Procedural pain Post-operative pain Disease-related pain Neuropathic pain Cancer pain Palliative and end of life care
Audience Response Question 3  Providing children with information regarding procedures and treatment they will receive will cause more anxiety and pain
A. True B. False
Nonpharmacologic Treatment Behavioral Methods – Enhance the ability to cope by allowing the child to gain some control of the situation and actively participate in treatment – Must take the developmental level of child into consideration
Examples include – Distraction soothing songs or stories – Guided imagery daydreaming – Therapeutic play
Providing truthful information about what will happen
Pharmacotherapy The Anti-inflammatory Drugs Aspirin – Use has declined since 1970s – Equally effective with ibuprofen but with better compliance and fewer adverse reactions
Acetaminophen – The most widely used antipyretic and mild analgesic for children – Be careful of daily cumulative doses as they are both weight and age specific
Pharmacotherapy The Anti-inflammatory Drugs (cont’d)
Non-steroidals –Widely used in children –Adverse gastrointestinal or renal events from shortterm use are rarer in children –Provide good post-operative analgesia
Selective cyclooxygenase-2 (COX-2) inhibitors –Few published studies of pediatric use
Pharmacotherapy The Opioids (cont’d) Indications –Postoperative pain, sickle cell and cancer pain
Low risk of addiction Potential for accumulation of active metabolites Continuous electronic monitoring –Respiratory-rate monitoring alone may be an inadequate predictor of impending apnea
Pharmacotherapy The Opioids Patient Controlled Analgesia – Extensive use with good efficacy and safety – Prevents delays in relieving episodic pain – Children as young as 6 years of age
Parent Controlled Analgesia – Formal education and documentation
Fentanyl Transdermal and Oral Formulations – Limitations due to strengths available
Patient Case 2 MG is a 12 year old with h/o left distal femur Osteosarcoma, s/p limb-sparing procedure, and now 18 months off therapy Developed left lateral distal thigh soft tissue recurrence, underwent local excision and re-resection Due to persistent positive margins now presents for AKA
Pharmacotherapy Local Anesthetics The amino-amides – Lidocaine, Bupivacaine, Ropivacaine
Topical preparations – Needle procedures – Laceration repair – Circumcision
Regional anesthesia – Epidural analgesia – Peripheral nerve blocks
Continuous Peripheral Nerve Block Provide site-specific local anesthesia – Extended post-operative analgesia – No hemodynamic changes and urinary retention
When compared to opioid analgesics – Improved functional outcomes – Lower incidence of N/V, pruritus, and sedation
Decreased opioid consumption Less pain intensity Greater patient satisfaction Curr Op in Anaesth 2008, 21:619-623
Patient Case 2 (cont’d) MG had 2 peripheral nerve blocks placed – Left femoral with Ropivacaine 0.1% at 6 mL/hr – Left sciatic with Ropivacaine 0.1% at 10 mL/hr
Stated pain goal: 5 Highest pain score: 4 Score most of the time: 0 Discharge Medications – Gabapentin, Docusate-Senna, Hydromorphone PRN, and Acetaminophen
Treatment of Cancer-Related Pain Multi-factorial sources –Tumor progression –Consequences of treatment
Aggressive dose titration! Side effect management Parental stressor Best managed with a multidisciplinary approach
Pharmacologic Management of Chronic Noncancer Pain Chronic Pain can be a family burden, affecting social functioning, and school attendance Nociceptive Pain Neuropathic Pain – Most commonly post-traumatic – Tricyclic antidepressants and anticonvulsant therapy use despite lack of controlled trials
Recurrent Headaches – Preventive and abortive therapies
Summary Well-controlled pediatric pain is an attainable goal when all of the following are in place 1. 2. 3. 4.
Age-appropriate pain assessment and reassessment Age-appropriate drug dosing Prescriber, parent, and patient education Combination therapy provided through a multidisciplinary team approach