|
|
Analgesics and Adjuvants
Health care professionals treating children often use medications that have not been specifically tested in children and that are thus not specifically indicated for pediatric use. This situation exists because children as a group are therapeutic "orphans"; the small number of children needing certain medications does not provide incentive for widescale testing. The administration of analgesics to children should follow the WHO ladder approach. Usual doses for children are listed in Table 8 and Table 10.
Acetamenophen and NSAIDs. Acetamenophen is a useful and relatively safe analgesic that provides effective relief of mild pain and enhances opioid effectiveness.466 The rectal route is available for children who cannot take medication orally; however, children do not like this route and may refuse to take the medication. Rectal administration is contraindicated for children who are neutropenic or thrombocytopenic and for those with mucositis. These contraindications and the irregular absorption of the rectal route limit its usefulness in treating severe pain.338
Because children with cancer are often thrombocytopenic, NSAIDs frequently cannot be used. They do, however, provide excellent analgesia for the child who is not at risk for bleeding because of thrombocytopenia or a coagulopathy and who is not at unusual risk of gastritis or ulceration (e.g., from the concurrent use of corticosteroids). NSAIDs effects on inflammation can be salutary, especially in the presence of bone pain. Evidence suggests that NSAIDs such as choline magnesium trisalicylate and salsalate have little effect on platelet function in normal subjects not at risk for bleeding.105 Even so, the use of these "platelet-sparing" NSAIDs in children at risk for bleeding is not recommended.
The administration of acetaminophen and NSAIDs varies according to the severity of the pain (Table 9). For very mild or intermittent pain, as-needed administration is appropriate. However, hospitalized children and their parents should be told to ask for the medication if pain occurs. An advocate may be appointed to assist the child and parents in requesting medications. For continuous or more severe pain, around-the-clock administration is necessary (Table 9).
Opioid analgesics. For moderate to severe pain, opioid analgesics are recommended. Some health care professionals are concerned about the potential for addiction in children, a risk that is rare in adult cancer patients.247 Although studies of the risks in children are lacking, no known aspect of childhood development or physiology increases the risk of physiologic or psychological vulnerability to chemical dependence. Therefore, withholding opioids from children with cancer is unwarranted.
Route of administration. Whenever possible, opioids should be administered orally. Many are available in a liquid form or suspension; often, those that are not commercially available in this form can be pulverized (with the exception of controlled-release drugs) and administered in a small amount of liquid or soft food. Parenteral administration is indicated when: (1) the child cannot take medication by mouth, for reasons such as obstruction, nausea, vomiting, and mucositis; (2) absorption may be compromised (e.g., as a result of chemotherapy-induced obstipation); (3) the pain is severe and requires timely management and a rapid titration to effect; (4) frequent and severe breakthrough or incident-related pain occurs; and (5) the oral route requires frequent administration of medication or large numbers of pills or liquid. Even with severe pain, once the opioid dose requirement is ascertained, the route can be changed over a few days from the intravenous to the oral route by using equianalgesic conversions (Table 11).
When parenteral administration is required, the intravenous or subcutaneous route can be used.339 Some children with cancer have implanted central catheters, which can be used; similarly, children who cannot take medication by mouth often have an intravenous catheter for the administration of fluids, chemotherapy, or antibiotics. Intramuscular injections should not be used, because "shots" are painful and frightening to children.
Transdermal fentanyl provides an alternative route for children with relatively constant pain who require larger doses of opioid analgesia. It is unsuitable for rapid-dose titration or for any patient with changing pain intensity. Currently-available preparations do not permit the delivery of drug at dosage rates low enough for young children.
Schedule and dose. Severe pain is an emergency, requiring the rapid titration of analgesia to provide relief within a few hours. Rapid titration involves frequent assessments and dosage adjustments. For example, because the peak effect of intravenously administered morphine occurs about 15 minutes after administration, the patient whose dose requirement is unknown could be given 0.1 mg/kg of morphine and be assessed every 15 minutes, with additional increments of 0.05 mg/kg administered until relief is obtained.
Opioids can be administered by intermittent boles injections, infusions, or infusions with "rescues." Unless the pain is truly intermittent and unpredictable, as-needed administration should not be used since delay between the request for medication and the administration results in poor pain management. In those isolated cases when as-needed administration is indicated and when "rescue" doses of medication are added to an infusion, the child needs an advocate (e.g., nurse, parent) to ensure prompt administration.
Intermittent bolus injections of morphine or its analgesic equivalent can be provided on an around-the-clock basis at a starting dose of about 0.1 mg/kg. Initial dose intervals are the same as those recommended for adults. Continuous infusion of morphine, at starting dose of 0.02 to 0.04 mg/kg per hour for children over 6 months of age has been well studied in postoperative pain and described in pain.202; 339 Continuous infusion avoids the extreme variations that may occur with intermittent intravenous doses and is indicated when intermittent doses (1) cause undue somnolence at the time of peak effect, (2) provide inadequate analgesia at the usual starting doses, or (3) must be administered more frequently than every 2 to 3 hours to provide adequate analgesia. Children receiving a continuous infusion should be offered "rescue" doses for breakthrough or poorly controlled pain regularly on the basis of their level of pain and the duration of the effect of the prescribed opioid.
Because of wide variability in opioid dose requirements,347 pain and side effects should be assessed frequently, with the dose.and interval adjusted for optimal relief. Many children require large doses of opioids; the process for dose increase and titration to effect is the same as in adults. To titrate to effect when a continuous infusion with rescue doses is used, the total amount of opioid administered (including rescue doses) is calculated for a specific time period, usually 8 or 12 hours. This amount is then added to the total amount of opioid to be infused over the next 8- or 12-hour period. Because four or five half-lives are required to reach a new steady state, increasing the infusion when pain is poorly managed will not by itself provide adequate, immediate relief. In fact, it could result in the administration of an unnecessarily large dose as soon as the infusion reaches a new steady state.
Agent. Morphine is the preferred starting agent for severe pain. Codeine and oxycodone can be used for moderate pain, although morphine and hydromorphone may be better tolerated by some children. Opioids such as hydromorphone, methadone,337 and fentanyl may be preferable when side effects are not easily controlled. Methadone use requires careful titration and appreciation of the potential for delayed somnolence because of its long half-life. Meperidine should be used only in exceptional circumstances such as hypersensitivity to morphine and hydromorphone and when single dose (e.g., for a procedure) or use for fewer than 2 days is anticipated.
PCA. PCA provides safe and effective analgesia in children old enough to understand the relationship among a stimulus (pain) and a behavior (pushing the button), and a delayed response (pain relief). Most children over the age of 7 understand this concept, and sometimes even younger children can learn to use PCA, but some may not have the cognitive or emotional resources to use it. Only one postoperative pain study has focused on the effectiveness of PCA with and without a basal infusion in contrast to the effectiveness of intramuscular morphine.46 One study addressed the efficacy of PCA for adolescents (age 18 or older) with cancer in treating mucositis after bone marrow transplantation.211 Patient-controlled dose and basal infusion have not been explored systematically in children with cancer.
Monitoring. Regular assessment of a patients vital signs and level of consciousness is necessary when parenteral opioids are used. Because of variable clinical situations and goals of treatment in children with cancer-related pain, professional judgment should be used to determine the presence, type, and frequency of monitoring. Because of wide interindividual and intraindividual variations in response, a child may have an adverse reaction, despite the most careful titration of doses and intervals.
Side effects. Young children may have difficulty communicating subjective symptoms like pruritus, nausea, constipation, and dysphoria; the preverbal child may show only generalized discomfort. If an infant or preverbal child becomes increasingly restless or irritable, despite an increased opioid dose, it is important to consider treatment of presumed side effects or a change to an alternative opioid. The pharmacologic approach to managing side effects in children is similar to that in adults. However, the assessment of side effects and pain relief should occur simultaneously.
One of the most feared side effects of opioid use is respiratory depression. In the dying patient, it may be due to the disease and not necessarily to the effects of opioids. In the patient who is not dying, naloxone-may be indicated. If naloxone is used, it should be titrated incrementally . until the patient resumes adequate respiratory effort. The initial dose of naloxone in the child is about 0.5 to 2 pg/kg, with the dose repeated about every minute. Physical stimulation, oxygen administration, and support of respiration can be used while titrating the naloxone to effect.
Adjuvants. Tricyclic antidepressants can be used for adults. In general, the starting dose should be low, (e.g. about 0.2 mg/kg of amitriptyline), and then increased to about 1 to 2 mg/kg daily. Tricyclic antidepressants should be used with care in children who have received large doses of cardiotoxic anthracyclines. A baseline electrocardiogram may be useful but is not required.
Stimulants such as dextroamphetamine and methylphenidate can also be used for children, with the goal being to provide additional analgesia and increased quality of awake time. The starting dose for both stimulants, 0.05 mg/kg, is gradually increased to effect with an upper limit of roughly 0.25 mg/kg per dose. Stimulants are given at times of desired wakefulness, such as morning and midday.
Go to the Assessment of Pain In Children Menu
Go to the Pain in Speical Populations Menu
Go to the Pain & HIV/AIDS Menu
Go to the HIVpositive.us Main Menu
74