Management of Postoperative Pain in Children

US Pharm. 2008;33(3):HS10-HS15.

Over the past two decades, pain assessment and management in children has greatly improved due in part to the development of age-specific pain assessment tools and a better understanding of the role of analgesics in this population. In the postoperative setting, different surgical procedures will produce varied levels of pain, and sound practices that account for the alterations in pharmacokinetics and pharmacodynamics that are present in children should be incorporated into the management of such pain. Many children still suffer from unnecessary pain due to misconceptions regarding pain control.¹ These misconceptions include the belief that children do not perceive pain the same way as adults, and some clinicians may believe that analgesics are associated with an increased incidence of toxicity in this population.² A thorough understanding of the assessment techniques and therapeutic interventions utilized for postoperative analgesia will allow the pharmacist to play an integral role in the management of the pediatric patient.

Assessment

Pain assessment tools utilized in the postoperative setting should be appropriate to reflect the needs of each child and should account for any limitations that may hinder accurate assessment. For example, children less than 4 years of age may be considered too young to properly utilize a self-report pain scale.³ A commonly used assessment tool is the Wong-Baker FACES Rating Scale, where children are asked to look at and choose from six different faces that depict expressions associated with no pain to varying levels of pain that may or may not be associated with crying. This tool is effective in children as young as 3 years old; however, its one-dimensional nature limits its usefulness in evaluating the behavioral effects that may accompany a painful experience.

With regard to the postoperative setting, one study recommended the use of two scales for pain assessment in the pediatric patient.³ These included the Face, Legs, Arms, Cry, Consolability (FLACC) scale for hospitalized patients and the Parents' Postoperative Pain Measure (PPPM) for discharged patients.^4,5 The FLACC scale provides a quantitative measure of the presence and severity of pain in children via assessment of pain-related behaviors.⁴ The PPPM scale is a 15-item checklist that allows parents to assess their child's pain.⁵ The COMFORT scale, comprised of six behavioral items and two physiologic items, has also been validated for use in the postoperative setting in children 0 to 3 years of age.⁶

Pharmacotherapy
Nonopioid Analgesics: Nonopioid analgesics, including nonsteroidal anti-inflammatory drugs (NSAIDs) and acetaminophen, play an important role as first-line agents in the management of mild-to-moderate pain in children.^7-12 Depending on the level of pain control required, these agents may be sufficient as the sole pharmacologic treatment or may be used adjunctively with opioids or other types of pain control. NSAIDs, in particular, have proven to be a popular method for analgesia in the postoperative setting. Their ease of dosing, widespread availability, parental acceptance, lack of opioid-type adverse effects, and the relative comfort of the practitioner in prescribing such drugs support their role in postoperative pain management. When used in combination with opioids, NSAIDs exhibit "opioid-sparing" effects. ⁸ Consequently, the patient is likely to experience fewer adverse effects associated with both analgesics.

Common adverse effects of NSAIDs include bleeding and gastrointestinal and nephrotoxic effects. However, one placebo-controlled study of ketorolac in postoperative infants showed no adverse effects on renal or hepatic function.⁹ NSAIDs are contraindicated in a number of pediatric patients, including those who are susceptible to renal or hepatic disorders, have increased bleeding risks, or are on other nephrotoxic agents or anticoagulants; use should also be avoided in neonates.¹⁰

Cyclooxygenase-2 (COX-2) inhibitors are starting to be evaluated in the pediatric patient.¹¹ However, their place in therapy remains to be fully elucidated. The current lack of studies and underwhelming evidence gives minimal support to the use of COX-2 inhibitors over NSAIDs for children.^10,12

Acetaminophen, an inhibitor of prostaglandin synthesis, is commonly used in the treatment of mild postoperative pain; however, compared to other agents, its analgesic potency remains low and ceiling effects may be observed.⁸ Acetaminophen is frequently used with codeine to enhance the overall analgesic effect. Loading and maintenance dosing regimens vary with age; newborns metabolize acetaminophen via sulfation pathways, while in adults metabolism occurs mainly via glucuronidation pathways in the liver. This difference leads to a slightly extended plasma half-life in the neonate.¹³ Consideration for use should always be given to patients with potential contraindications (e.g., viral hepatitis, decreased glutathione stores). Recommended dosing for nonopioid analgesics in children can be found in TABLE 1.

Opioid Analgesics: With proper dosing and appropriate assessment and monitoring, opioid analgesics can be considered for the treatment of moderate-to-severe postoperative pain. The underutilization of opioids in the pediatric population may arise from the misconception that pain perception is diminished secondary to immature pain-processing pathways. However, anatomical components that facilitate pain perception are well-formed at 25 weeks' gestation, although the ability to mount descending analgesic responses develops later during infancy.^14,15Opioid receptors also develop during gestation and are considered to be widely distributed.^14,15 The neurobiology of pain in infants and children dictates that opioids can provide effective analgesia. Nonetheless, it is imperative that clinicians understand the pharmacokinetic and pharmacodynamic factors associated with the use of opioid analgesics in the pediatric population before these agents are considered.

The response to an opioid analgesic varies greatly by age. In neonates, opioids are more likely to induce respiratory distress secondary to poor ventilatory reflexes.¹⁵ With regard to drug metabolism, newborns may be at an increased risk of opioid accumulation due to immature hepatic enzymes. Additionally, the renal excretion of opioids may be diminished secondary to decreased glomerular filtration rate and renal tubular secretion capacity.¹⁵ Newborns and infants have a greater percentage of total body water, thereby producing an alteration in the volume of distribution of these agents. The half-life of morphine is markedly increased in neonates compared to adults (six to eight hours versus two hours, respectively).¹⁶ By adolescence, the metabolism and excretion of opioids reach the same levels seen in adults.

Morphine has been extensively studied for the management of pain after major surgery in children.^17,18 It is considered a favorable choice because it is well tolerated and can be given through several different routes of administration, although oral administration is typically avoided because of variable bioavailability.¹⁹ Other opioids that have been utilized in this setting include fentanyl, hydromorphone, codeine, and tramadol.^12,19,20 Fentanyl and hydromorphone are suitable alternatives to morphine secondary to their ease of titration when given parenterally. Because codeine and tramadol have the ability to produce weaker analgesic effects, use is typically limited to the management of moderate to moderately severe pain associated with minor procedures.¹⁹ Additionally, tramadol has been associated with increased postoperative nausea and vomiting, further restricting its use. ²⁰

The recommended dosing for opioid analgesics for the management of postoperative pain in children can be found in TABLE 2. These agents should be administered around the clock, rather than as needed, to avoid "chasing" increases in pain severity. As previously mentioned, children are at an increased risk for the development of opioid-induced respiratory depression and are not invulnerable to other adverse effects (e.g., pruritus, sedation); therefore, adherence to dosing and titration guidelines is essential. Monitoring of adverse effects should occur along with, and as frequently as, the assessment of the child's pain.

The use of opioid infusions (e.g., patient-controlled analgesia [PCA], continuous IV infusions) has become commonplace in the management of pediatric postoperative pain. Continuous IV infusions provide consistent analgesia and are frequently used in neonates, infants, and select children with severe pain who have undergone major surgery or have been admitted to intensive care units.²¹ PCA has been shown to be an effective means of pain control in older children (above 5 to 7 years of age) and adolescents who can understand the use of such a device. PCA provides the patient with analgesia by maintaining steady serum opioid concentrations and allows for patient-specific dose adjustments. Morphine is considered the opioid of choice for PCA and continuous IV infusions, with hydromorphone reserved for those who cannot tolerate, or do not achieve analgesia with, morphine.

Adjuvant Analgesics
Local anesthetics, including bupivacaine and ropivacaine, have frequently been used in children for analgesia during and immediately following surgery; however, it is important to be aware of their associated risks. It can be particularly difficult to detect intravascular infiltration in children, and cardiovascular toxicity and seizures have been reported in this population.²⁰ When added to a single injection of a local anesthetic epidural solution, clonidine 1 to 2 mcg/kg has enhanced the duration and effectiveness of the local anesthetic.²²

As an N -methyl-D-aspartate (NMDA) receptor antagonist, dextromethorphan is another adjuvant analgesic agent that has shown mixed results in postoperative pain control. One study demonstrated that a one-time preoperative dose of 0.5 to 1 mg/kg of oral dextromethorphan did not reduce postoperative morphine consumption in children.²³ A potential benefit to using dextromethorphan is its lack of unwanted opioid adverse effects. Ketamine, also an NMDA receptor antagonist, may be beneficial in epidural administration due to the lack of observed respiratory depression.²⁰ One meta-analysis identified a median dose of 0.4 mg/kg of ketamine used among all trials examined, with some evidence to support the use of ketamine in children. ²⁴ However, limitations to using this agent as adjunctive therapy may include the relative difficulty of obtaining preservative-free products for epidural use and the potential of ketamine to induce emergence phenomena, nausea, and vomiting.

Summary

Inappropriate management of postoperative pain in children can result in changes that could have a lasting negative impact. Goals of therapy should include providing complete pain relief while minimizing adverse physiologic and psychological effects. Pharmacists can play a crucial role in implementation, initiation, and monitoring of appropriate analgesic therapies²⁵ and should participate in age-appropriate preprocedural teaching and postoperative counseling. Pharmacists can also partake in research that focuses on the integration of "adult" medicine into the pediatric population and can be key decision-makers in the development and implementation of staff education, standardized order sets and protocols, and thorough follow-up procedures.

Future directions for pediatric postoperative pain management include the need for further studies on adjuvant nonopioid pain control as well as continued validation of pediatric postoperative pain measurement scales.

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