CHAPTER 14

Pediatric Pain and Symptom Management

Kevin Madden, MD, and Richard Goldstein, MD, FAAP

Ill or injured children experience distressing physical symptoms, particularly in the case of illness or injury that is chronic or life-limiting. The appropriate management of such symptoms is fundamental to minimizing discomfort and optimizing quality of life. Pain can not only diminish a child’s physical well-being but also can affect psychological, social, and spiritual health. Children experiencing poorly controlled pain will withdraw interpersonally and be unable to engage in the activities that make their life, however limited, meaningful. Similarly, a child troubled by nausea will experience distress from the symptom while also losing the simple pleasure of eating and its accompanying comforts. Symptom management improves the lives of children who are medically fragile.

Parents or caregivers of children who are seriously ill worry most about their child’s symptoms not being satisfactorily controlled. Studies of dying children have noted that distressing symptoms often go untreated. Research investigating the symptoms and experience of children dying from cancer found that most of the children experienced fatigue, pain, dyspnea, anorexia, nausea and vomiting, and constipation in the last month of their lives (Figure 14.1). Similar findings have since been noted in other populations. Children with neurologic impairment are particularly at risk because of their limited verbal abilities and atypical responses to pain. Symptom management of seriously ill children has been improved significantly since early studies. As more children with chronic and serious illnesses are cared for and sometimes die at home, the management of their illnesses will increasingly involve their primary care pediatrician.

This chapter reviews the basic medical approaches to pain and symptom management in children, particularly those with serious illnesses. In addition to pain, approaches to nausea, anorexia, fatigue, secretions, and delirium are presented. The focus is on the medical management issues a primary care pediatrician may attempt to manage in the community setting. When the primary care pediatrician is insufficiently familiar with such treatment, consultation with pain or palliative care specialists is appropriate.

Pain

Pain is an integrated biophysical and “existential” construct. It involves complex mechanisms of nociception modulated by biochemical factors, neuroplasticity, genetic and familial factors, and an individual’s past experience with painful events. Each child experiences pain in a unique way and quickly develops learned behaviors related to it. As such, no simple correlation exists between the objective degree of injury and the experience of pain. More accurately, physical, psychological, interpersonal, and existential factors all contribute in important ways to the experience of pain. A comprehensive approach to pain addresses all these elements.

Figure 14.1. The presence and degree of distress from specific symptoms in the last month of life.

Adapted with permission from Wolfe J, Grier HE, Klar N, et al. Symptoms and distress at the end of life in children with cancer. N Engl J Med. 2000;342[5]:326–333.

Assessment

The 2 basic types of pain are nociceptive and neuropathic. An understanding of the presentation of each type can help differentiate the source of pain in children. Nociceptive pain is the activation of peripheral nerve receptors when noxious stimuli cause tissue damage, and its intensity is related in part to the location and the amount of damage. Somatic pain refers to nociceptive pain from musculoskeletal, bony, or superficial sources (eg, skin, mucosa). Deep somatic pain tends to be localized and concentrated and is described as stabbing, aching, or throbbing (eg, bone pain is deep and aching). Superficial somatic pain is sharper and can be burning or pricking. The source of nociceptive pain can also be visceral. Visceral pain is usually poorly localized; can be described as cramping, gnawing, or pressure; and may follow daily patterns of varying intensity.

Neuropathic pain is caused by injury or dysfunction of the central nervous system (CNS) or peripheral nerves. It can be described as burning, tingling, shooting, or scalding. Its presence points to neuropathies, CNS insult, or evolving damage to the nervous system. Understanding whether the source of pain is somatic, visceral, or neuropathic helps guide treatment decisions.

Pain should be a part of the medical evaluation of every child. Pain is phenomenological and thus, although its existence is “real” and “objective,” it can be experienced and described only by the affected person. Fundamentally, the patient’s report of the presence or severity of pain is the key to the assessment. In children, especially children with developmental issues, objective assessment tools may be useful to identify the presence of pain and quantify its severity. In most patients these scales are also helpful in understanding the symptom of pain over time.

Standardized pain scales are used to assess the intensity of pain. Analog pain scales, which generally score intensity on a scale of 1 to 10, have some reliability when used in the same patient over time (Figure 14.2). Younger children may have difficulty with the concept of quantity or the meaning of greater intensity. An important modification of the analog scale for children with impaired communication skills or cognition is the Individualized Numeric Rating Scale, on which parental or caregiver observations of their child’s facial expression, body movements, activity and interaction, crying, and ability to be consoled as they experience worsening pain are used to label the points of the scale.

For children older than 3 years, the Wong-Baker FACES Pain Rating Scale (Figure 14.3) is often used. After showing children the faces, they are instructed that each face is for a person who has no pain (no hurt), some pain, or a lot of pain. The child is then asked to choose the face that best describes how the child is feeling. More comprehensive pain assessment tools are available that also assess function and mood, but they are less widely used. The perspective of parents or caregivers and others familiar with the child is crucial to any assessment of a child’s pain.

Figure 14.2. Visual analog pain scale.

Reprinted with permission from McCaffery M, Pasero C. Pain: Clinical Manual. 2nd ed. St Louis, MO: Mosby; 1999.

Figure 14.3. Wong-Baker FACES Pain Rating Scale.

Reprinted with permission from Wong-Baker FACES Foundation [2014]. Accessed August 17, 2019, www.WongBakerFACES.org.

The child in pain must be relieved of it; however, it is advantageous to make a strong effort to understand the source of the pain and manage conditions amenable to nonpain medication. For example, chest pain may be caused by candidal esophagitis or abdominal pain resulting from constipation. Thinking clearly about the etiology of pain rather than simply providing analgesic agents in a reflexive manner has the benefits of preserving alertness, sparing side effects, and sustaining the least impaired quality of life. Pain can be eliminated by eliminating the underlying condition responsible for it. The optimal management of pain also includes addressing psychosocial and spiritual distress and making efforts to enhance a child’s function as part of an integrated approach to pain-related distress.

Medical Management

Opioids are the pharmacologic mainstay of pain management. Familiarity with the basic principles of treatment with these agents is fundamental to care for the child with serious acute and life- limiting illness. In cases of complex pain or those involving daunting polypharmacy, it may be best to seek guidance from pain or palliative care specialists. Additionally, certain medications (ie, methadone, selective norepinephrine reuptake inhibitors) or invasive approaches (ie, intrathecal pumps, regional blocks, surgical or radiotherapeutic approaches to pain control), or the management of chronic pain, particularly in adolescents, should involve consultation with or referral to pain and palliative care specialists.

The use of opioids in children since approximately 1990 roughly parallels wider trends observed in their use in adults. The 1990s and early 2000s saw a dramatic increase in the number of opioid prescriptions in the United States, motivated by the assessment that pain in seriously ill children was being undertreated. Changing prescribing practices also heralded a new public health crisis, the opioid-overdose epidemic. Currently, opioid overdoses are the leading cause of death of Americans younger than 50 years. The philosophical pendulum is now swinging back towards a more scrutinized prescribing environment. Some commercial pharmacies limit new prescriptions of opioids for noncancer pain to a 7- to 10-day supply, and many state medical boards now require physicians to review prescription drug monitoring program databases on a routine basis. Parents have responded to this widely publicized phenomenon with renewed caution about opioids, while seeking the benefits of appropriate use. Proposing an opioid for a child now demands considerable investment by the physician to provide a comprehensive pain plan that highlights consistent reassessment of the need for an opioid, directly addresses the specter of dependency before initiation of an opioid, and reassurance that the child’s best interest will always be the focus of treatment.

Pain must be understood as a multidimensional symptom with a meaning for the individual that influences the experience of it, worthy of its own attention. In the context of “total pain,” other etiologies of pain should be considered, assessed, and managed, especially when a child’s or parent’s/caregiver’s report of pain intensity seems incongruous with the amount of opioid provided. Total pain conceives of pain as having 4 interrelated domains: physical, psychological, social, and spiritual. The use of opioids may unintentionally alleviate psychological, social, and spiritual pain as the limbic system also possesses mu receptors, but it cannot substitute for attention to all the elements of pain. Activation of these specific mu receptors upregulate mood, which can easily become intertwined and confused with relief of physical pain.

Dose escalation should proceed until the pain is controlled, provided that side effects are tolerable. Opioids have no maximum or “ceiling” dose. The child on long-term opioid treatment often receives surprisingly high doses yet, provided the treatment is successful in controlling pain, is comfortable and functional. Generally, infants younger than 6 months should be started at one-third the general pediatric dose. Anticipated side effects of opioids include constipation, pruritus, and nausea and vomiting. The pruritus and nausea and vomiting are usually short-lived, disappearing in a week, but constipation persists. All patients on scheduled opioids should also receive scheduled doses of stool softeners and stimulant laxatives.

Parents or caregivers and some physicians may overestimate the benefit of distraction in pain management. Distraction is best thought of as an assessment tool and may be an adjunct to but not a treatment for pain. If a child can be substantially distracted from the pain for a significant period, the pain need not be managed with medication. If the child’s distress is apparent despite the distraction, however, pharmacologic intervention for the pain is necessary. What must be avoided is a distressed child engaging in the distraction to please adults while the pain goes unabated. Similarly, the use of placebos has no place in the treatment of pain.

The World Health Organization 2-step approach to pharmacologic management of pain is the most important guide to pain management in children. It presents a stepwise and additive approach to “capture” a child’s pain as well as to augment the pharmacologic treatment of pain. The model is premised on using a 2-step strategy, dosing at regular intervals, using the appropriate route of administration, and individualizing treatment to the particular child.

The child with mild pain who has not received any analgesic medication is managed with oral analgesics, such as acetaminophen and ibuprofen (step 1). In certain cases, intravenous acetaminophen or ketorolac tromethamine may be used. Adjuvants may be added if appropriate. Acetaminophen can be given orally or rectally. Compounded ibuprofen can be given rectally. The topical application of these agents in ketoprofen cream or aspirin cream may also be of benefit. Rarely, a role may exist for a cyclooxygenase-2 inhibitor. All nonsteroidal anti-inflammatory drugs have ceiling doses and gastrointestinal toxicities. With the exception of acetaminophen and celecoxib, all affect platelet function and hemostasis.

Adjuvants are non-analgesic drugs that are helpful in the management of a child’s pain. For example, anxiety experienced by a child who is medically fragile may potentiate the child’s pain and distress, even at step 1. A benzodiazepine may be helpful in such cases, but it should be prescribed with an awareness of other medications. An alternative to benzodiazepines for anxiety is the antipsychotic agent haloperidol. At very low doses it provides an anxiolytic effect without sedation or the synergism with opioids that can result in respiratory depression. A lidocaine patch can help with some somatic pain. Certain forms of mild to moderate pain (ie, neuropathic pain) may be adequately managed with gabapentin or pregabalin, minimizing the use of opioids.

Step 2 addresses children with moderate to severe pain and involves the addition of opioids to the treatment plan (Table 14.1). “Weak opioids” (eg, codeine, tramadol hydrochloride) are no longer recommended. Research has shown that codeine may be a weaker analgesic than a standard dose of many nonsteroidal anti-inflammatory drugs, and it has a ceiling effect. The oral bioavailability of codeine is widely unpredictable, at 15% to 80%. Most importantly, codeine is a prodrug that must be metabolized by the liver into morphine. This is problematic because it is estimated that 35% of children do not metabolize codeine in the anticipated manner, resulting in great uncertainties in a calculated effect. The use of tramadol hydrochloride is only weakly recommended because of concerns about risks for seizures and hyperserotonergic symptoms with its use.

Abbreviations: IV, intravenous; max, maximum; N/A, not applicable.

^a Only for children >10 years of age.

^b Dose equivalent to oral or IV dose.

^c Dose equivalent to oral dose.

When pain persists or worsens, morphine, hydromorphone, and oxycodone are recommended initial choices. Doses are escalated until pain is controlled, using the least invasive form of administration necessary. This step may involve the addition of controlled-release preparations of opioid or methadone, while using shorter-acting agents for breakthrough pain. To calculate the as-needed dose for breakthrough pain, a general rule is that the as-needed dose is 10% to 15% of the 24-hour total opioid dose or its equivalent, given orally every 3 to 4 hours.

An in-depth discussion of methadone and fentanyl citrate exceeds the scope of this chapter, but it is worth making several points about them. Neither has active metabolites, making them important options for patients with renal failure in whom accumulated metabolites from other opioid agents can cause myoclonus, confusion, or hyperalgesia. Fentanyl citrate, a potent analgesic, is available in a transdermal patch, which is an important nonintra-venous, non-oral option for children having difficulty swallowing. The child must have adequate body fat, because the drug is deposited across the rate-limiting membrane into fat reservoirs and is absorbed from that reservoir into the child’s bloodstream. Methadone has some distinct analgesic advantages. It is inexpensive, its half-life allows for more convenient twice-a-day or 3-times-a-day dosing, and it is especially helpful in managing neuropathic pain. It is complicated to dose, however, and its long and variable half-life make it a more complicated choice for those not familiar with its use.

The management of moderate and severe pain over time can result in the development of difficult unintended effects, including sedation, nausea and vomiting, pruritus, and urinary retention. At high doses or when metabolites accumulate, patients may develop delirium, myoclonus, or hyperesthesia. Opioid rotation can be quite helpful in these situations. This method involves converting 1 form of opioid to an equivalently analgesic dose of another.

Rotation of the opioid agent (ie, using a different opioid) holds the promise of maintaining analgesia with lesser amounts of the newly introduced drug and eliminating side effects. Tolerance is the term used to describe the need over time for increased amounts of a specific opioid to achieve the desired analgesic effect. Although opioids lack a ceiling dose, higher doses may have an accompanying increase in adverse effects (ie, the emergence of the intolerable side effects noted previously, the accumulation of toxic metabolites, or high cost resulting from the required amounts of the drug). Because of multiple mu opioid peptide receptors as well as different selectivity of opioids for specific mu opioid peptides, the cross-tolerance from 1 opioid to another is not complete. An equianalgesic dose of another opioid will require less of the medication and achieve a more favorable balance between analgesia and side effects. See Box 14.1 for an example of opioid conversion.

Physicians lacking experience in pain management may be concerned about the difficulty of addressing uncontrolled pain. Because expert and effective management is a critical skill in the care of seriously ill children, especially those facing the end of life, the primary care physician may choose to consult with palliative care or pain treatment specialists to ensure that the child’s needs are adequately addressed. Alternatively, hospice medical directors can provide palliative care consultations if hospital-based teams are not available.

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