Abstract
Children present unique challenges in the management of postoperative pain. Differences in brain development and drug metabolism influence dosing regimens. Assessment of pain is affected by a child’s ability to self-report, and behavioral assessment scales, while validated and widely used, have important limitations. Despite this, most opioid medications and adjuncts are used safely in the pediatric population. Infants under 6 months of age may need reduced dosing schedules due to reduced hepatic clearance of many medications including commonly used opioids. Aspirin should be avoided due to the risk of Reye syndrome. The prodrugs codeine and tramadol should be avoided in the preadolescent population due to cytochrome-P450 (CYP) 2D6 subtype variations that rapidly metabolize them to the active form causing symptoms of opioid overdose and, in rare cases, death. Patient-controlled analgesia, dosed appropriately, is a safe and effective method of pain control for children with moderate to severe postoperative pain. Regional anesthesia plays an important role in postoperative pain control in children. Common techniques include caudal injections for lower abdominal, urologic, and lower extremity procedures; epidural catheter placement for intraabdominal and thoracic procedures; and a variety of peripheral nerve blocks as appropriate. Performance of regional anesthesia under general anesthesia or deep sedation is an accepted practice that has been shown in large cohorts to meet safety standards for performance of regional anesthesia.
Keywords
acute pain, pain assessment, patient-controlled analgesia, pediatric pain, pharmacology, regional anesthesia
Historically underrecognized and undertreated, pediatric pain management has improved dramatically since the early 1990s. Advances in pain assessment, pharmacologic studies of opioid and nonopioid analgesics in children, and development of physician-directed hospital-based acute pain services have been important factors in this development.
Anatomic and Physiologic Differences
The rational use of analgesics in pediatric patients, particularly neonates and infants, requires recognition of maturational changes that occur after birth in body composition and core organ function.
Total body water represents about 80% of body weight in full-term newborns. This drops to 60% of body weight by 2 years of age with a large proportional decrease in extracellular fluid volume. The larger extracellular and total body water stores in infancy lead to a greater volume of distribution for water-soluble drugs. Newborns have smaller skeletal muscle mass and fat stores, decreasing the amount of drug bound to inactive sites in muscle and fat. These stores increase during infancy.
Cardiac output is relatively higher in infants and children than adults and is preferentially distributed to vessel-rich tissues such as the brain, allowing for rapid equilibration of drug concentrations. Immaturity of the blood-brain barrier in early infancy allows increased passage of more water-soluble medications such as morphine. This combination of increased blood flow to the brain and increased drug passage through the blood-brain barrier can lead to higher central nervous system (CNS) drug concentrations and more side effects at a lower plasma concentration.
Renal and hepatic blood flow is also increased in infants relative to adults. As glomerular filtration, renal tubular function, and hepatic enzyme systems mature, generally reaching adult values within the first year of life, increased blood flow to these organs leads to increased drug metabolism and excretion.
Both the quantity and binding ability of serum albumin and alpha-1-acid glycoprotein (AAG) are decreased in newborns relative to adults. This may result in higher levels of unbound drugs, with greater drug effect and toxicity at lower overall serum levels. This has led to lower local anesthetic dosing recommendations in neonates and young infants, although neonates have shown the ability to acutely increase AAG levels while on continuous local anesthetic infusions. The difference in serum protein quantity and binding ability disappears by approximately 6 months of age.
Neurotransmitters and peripheral and central pathways necessary for pain transmission are intact and functional by late gestation, although opiate receptors may function differently in the newborn than in adults. Cardiorespiratory, hormonal, and metabolic responses to pain in adults have also been well documented to occur in neonates.
The spinal cord and dura mater in the newborn infant extend to approximately the third lumbar (L3) and third sacral (S3) vertebral level, respectively, and reach the adult levels of approximately L1 and S1 by about 1 year of age. The lower-lying spinal cord in young infants is thus theoretically more vulnerable to injury during needle insertion at mid to upper lumbar levels. The intercristal line connecting the posterior superior iliac crests, used as a surface landmark during needle insertion, crosses the spinal column at the S1 level in neonates versus the L4 or L5 level in adults. There is less, and more loosely connected, fat in the epidural space in infants versus adults, explaining in part the relative ease with which epidural catheters inserted at the base of the sacrum can be threaded to lumbar or thoracic levels in infants and small children.
Pain Assessment
Depending on developmental age and other factors, the pediatric patient may be unable or unwilling to verbalize or quantify pain similar to his adult counterpart. Nonetheless, a number of developmentally appropriate pain assessment scales have been designed for use in both infants and children. They are based on self-report, behavioral, and/or physiologic measures ( Table 17.1 ) and have been tested, validated, and employed in research protocols ( Table 17.2 ). Children over approximately 8–10 years of age may be able to use the standard adult numeric rating or visual analog scale to self-report their pain. Specialized self-reporting scales are available for children and can be used in patients as young as 3 years of age ( Fig. 17.1 ). Behavioral or physiologic measures are available for younger ages and for developmentally disabled children ( Table 17.3 ).
| Age | Self-Report Measures | Behavior Measures | Physiologic Measures |
|---|---|---|---|
| Birth to 3 years | Not available | Of primary importance | Of secondary importance |
| 3 years–6 years | Specialized developmentally appropriate scales available | Primary if self-report not available | Of secondary importance |
| >6 year | Of primary importance | Of secondary importance | — |
| Measurement Tool | Domain Assessed |
|---|---|
| Behavior Score | Postoperative pain |
| Beyer Oucher Scoring System | Postoperative pain |
| CHEOPS | Postoperative pain |
| CHIPPS | Postoperative pain |
| COMFORT Scale | Postoperative pain |
| CRIES Scale | Postoperative pain |
| FLACC, rFLACC | Postoperative pain, cognitively impaired |
| NCCPC-PV | Postoperative pain, nonverbal, developmentally delayed |
| Objective Pain Discomfort Score | Postoperative pain |
| Objective Pain Score | Postoperative pain |
| Objective Pediatric Pain Scale | Postoperative pain |
| Observational Pain Scale | Postoperative pain |
| PPMS | Postoperative pain |
| Wong-Baker Faces Scale | Postoperative pain |
| Categories | Scoring 0 | Scoring 1 | Scoring 2 |
|---|---|---|---|
| F ace | No particular expression or smile | Occasional grimace or frown, withdrawn, disinterested | Frequent to constant frown, clenched jaw, quivering chin |
| L egs | Normal position or relaxed | Uneasy, restless, tense | Kicking, or legs drawn up |
| A ctivity | Lying quietly, normal position, moves easily | Squirming, shifting back and forth, tense | Arched, rigid, or jerking |
| C ry | No cry (awake or asleep) | Moans or whimpers, occasional complaint | Crying steadily, screams or sobs, frequent complaints |
| C onsolability | Content, relaxed | Reassured by occasional touching, hugging, being talked to, distractable | Difficult to console or comfort |
Nonopioid Analgesics
Acetaminophen
Acetaminophen (paracetamol) is very commonly used in pediatric patients, alone or in combination with other analgesics. It can be administered rectally in the perioperative period in infants or children for whom oral intake is not an option. Due to variable and slower adsorption with rectal dosing, a higher initial dose may be needed for rectal administration ( Table 17.4 ). Suppository insertion prior to surgical incision does not appear to significantly alter acetaminophen kinetics and may result in more timely analgesia in the early postoperative period. Higher dose rectal acetaminophen has been shown to be equi-analgesic to intravenous ketorolac following tonsillectomy and to have a significant opioid-sparing effect in children undergoing outpatient surgery. Intravenous acetaminophen is also appropriate in patients in whom oral intake is not an option. Blood levels via this route are more reliable than the rectal form.
| Medication | Dose (mg/kg) | Total Single Dose (mg) | Dosing Interval (h) | Maximum Daily Dose (Pt < 60 kg) (mg/kg) | Maximum Daily dose (Pt ≥ 60 kg) (mg) |
|---|---|---|---|---|---|
| Acetaminophen a (oral) | 10–15 mg/kg | 650–1000 | 4 | 75–100 | 4000 |
| Acetaminophen a , b (rectal) | 35–40 mg/kg loading dose; 20 mg/kg thereafter | Less defined | 6 | 75–100 | 4000 |
| Acetaminophen a (intravenous) | 10–15 mg/kg | 650–1000 | 4–6 | 75–100 | 4000 |
| Ibuprofen | 6–10 mg/kg | 400–600 mg | 6 | 40 | 2400 |
| Naproxen | 5–6 mg/kg | 250–375 mg | 12 | 24 | 1000 |
| Ketorolac | 0.3–0.5 mg/kg IV | 15 mg < 50 kg; 30 mg > 50 kg | 6 | 2 (IV) | 120 |
| Tramadol | 1–2 mg/kg | 100 mg | 6 | 8 | 400 |
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