The care of children undergoing painful medical procedures has improved considerably over the past decade. Factors contributing to these favora* ble changes include the recognition that pain can have deleterious physical and psychiatric effects, the development of safer, more predictable analgesics, and the implementation of stringent safety guidelines. On the heels of the realization that pain-free procedures are a worthy and often obtainable goal, the current cost-conscious health-care climate has begun to influence current practice further by mandating that treatment be cost effective.
This article reviews recent developments in pharmacologie and nonpharmacologic methods of alleviating pain and anxiety in children during medical procedures and provides a basis for their use. It includes a discussion on analgesia and angiolysis methods that are appropriate for use in the emergency department (eg, laceration repair and fracture repair) and in subspecialty settings where painful procedures (eg, bone marrow aspiration) often are undertaken. While it is not expected that this review alone will provide a sufficient basis for the practitioner to begin using unfamiliar techniques, the references provided along with assistance from experienced personnel should make these techniques accessible to the interested reader.
CHOOSING THE PROPER SEDATIVE TECHNIQUE
Selecting the optimal means for achieving periprocedural comfort requires preliminary consideration of the following questions:
1. Is the procedure painful? If so, treatment should include a medication with analgesic properties. An anxiolytic may be useful as well, but should not be relied on singularly. Even when only one part of the procedure is painful (ie, injection of the local anesthetic for laceration repair), analgesia still should be provided.
2. Does the child need to be motionless? Nonpainful procedures such as an echocardiogram or magnetic resonance imaging (MRI) require a motionless patient to obtain optimal results. The goals in these settings differ from those associated with painful procedures. Generally, analgesics are not required, but rather a medication that will ensure relaxation or sleep despite mild physical stimulation or loud noises.
3. What is the duration of the procedure? This is often the most important determinant in the choice of technique. Ideally, the effects of the sedative should not last significantly longer than the procedure itself. The child with prolonged alterations in. mental status will need to linger in the sedating facility and often will require direct supervision by trained personnel, placing costly and undue burdens on the busy emergency department or clinics with limited resources. The duration of a procedure may not be readily predictable but, more often than not, exceeds the estimated time. As a result, the sedative used ideally would have a rapid onset and offset, and thus be easily titrated.
4. What is the expertise of the practitioner performing the sedation? The sedative technique selected should be consistent with the knowledge and experience of involved personnel. The supervising practitioner should have an extensive knowledge of the effects and hazards of all medications used.
5. What safety resources are available? The American Academy of Pediatrics (AAP) has recommended minimal levels of monitoring and personnel, which correspond to the level of desired sedation. As a result, the resources of the sedating facility, in part, dictate the extent of sedation used.
6. What is the patient's NPO status? Protective airway reflexes are compromised to varying degrees depending on the choice of sedative agent, dose, and the baseline medical condition. If a painful medical procedure is planned, and NPO status is certain, then sedatives that may result in the loss of protective airway reflexes can be used with reasonable safety. The trauma patient, though, should be assumed to have a full stomach and therefore is not usually a candidate for deep sedation in the absence of artificial protection of the airway. In the case of trauma, the NPO interval is determined by the interval between the last meal and the time of the injury, rather than the interval between the last meal and the proposed administration of the sedative.
AMERICAN ACADEMY OF PEDIATRICS GUIDELINES
In order to encourage the safe administration of sedatives to pediatrie patients, the AAP promulgated safety guidelines in 1987, which were revised in 1992. ' The impetus for these guidelines was a 1983 report in the Journal of the American Dental Association that described life-threatening complications from sedatives administered during dental procedures in H children.2 The AAP recognizes two general states of sedation. Conscious sedation is defined as a medically controlled state of consciousness that is associated with: 1 ) maintenance of protective airway reflexes, 2) continuous and independent maintenance of airway patency, and 3) appropriate response to physical stimulation or verbal command, eg, "open your eyes." Deep sedation is defined as a medically controlled state of depressed consciousness or unconsciousness from which the patient is not easily aroused. It may be accompanied by a partial or complete loss of protective airway reflexes, and the inability to independently maintain a patent airway and respond purposefully to physical stimulation or verbal command. While the details of the AAP's safety guidelines are beyond the scope of this review, briefly, they include specific recommendations for personnel, equipment, documentation, and presedation fasting for given levels of sedation. The probability of an adverse occurrence is minimized when AAP guidelines are strictly followed, and personnel involved with sedation of children should be familiar with this document.
Chloral hydrate, a mild sedative, has been used in children for decades with an excellent safety record. In doses of 25 to 100 mg/kg administered orally, it will induce sleep lasting for 3 to 6 hours in the majority of children. The major drawbacks of chloral hydrate are its relatively long time to onset and its long duration of action. Because chloral hydrate lacks analgesic properties, it is not suitable for use as a primary agent for painful procedures. Chloral hydrate used as a first-line sedative for radiological procedures although a significant number of children require alternative therapy. Chloral hydrate has been reported to cause liver tumors in laboratory animals, but there is no evidence that children receiving sedative doses are at increased risk. The AAP has issued a statement that addresses this concern.3
Another commonly used sedative technique is the combination of intramuscular meperidine (Demerol, Sanofi Winthrop Pharmaceutical, New York, New York), promethazine (Phenergan, Wyeth-Ayerst Laboratories, Philadelphia, Pennsylvania), and chlorpro' mazine (Thorazine, SmithKline Beecham Pharmaceuticals, Philadelphia, Pennsylvania), commonly known as DPT. Because of its analgesic and sedating properties, this drug combination traditionally has been used for painful procedures. In recent years there has been a trend toward decreased use of DPT because of its unpredictability, relatively long duration of action, and side effects such as respiratory depression. In a prospective study of DPT complications, 4 of 95 children developed respiratory depression at usual or less-than-recommended doses.4 In a retrospective review of 487 children who received DPT for emergency procedures, 3 developed clinically significant respiratory depression necessitating the administration of" intravenous (IV) naloxone.5 These reports did not indicate the time required for the sedative effects to abate or at what point the children were ready for discharge.
The most compelling reason for abandoning DPT and chloral hydrate is the recent development of safer, more predictable agents. The ideal sedative agent has analgesic, anxiolytic, and amnestic properties, few or no side effects, a short onset and duration of action, and is inexpensive. Although none of the drugs discussed here fulfill all of these requirements, they begin to approach that ideal.
Because of their ability to provide analgesia without loss of consciousness, opioids have long been the mainstay for relieving periprocedural pain in adults and children. Although morphine and meperidine are used most commonly, because of their relatively long duration of action, they are less desirable than more recently introduced agents, especially for short painful procedures. Fentanyl, a synthetic opioid agonist that is approximately 100 times more potent than morphine, has gained widespread popularity because of its rapid onset, short duration, and predictability. In doses of 1 to 3 Jig/kg, fentanyl provides moderate analgesia of 30 to 40 minutes duration. Reporting retrospectively on 2 000 cases of racial lacerations in children, Billmire et al6 reported excellent suturing conditions with the administration of 2 to 3 µg/kg of IV fentanyl. Three instances of respiratory depression occurred, but were readily managed with IV naloxone. Fentanyl recently has become available in a lozenge form that resembles a lollipop and is referred to as an oralet. Sufentanil and alfentanil are synthetic opioids that are related to fentanyl.
Sufentanil is approximately seven times more potent than fentanyl and has a slightly shorter duration of action. Alfentanil, which is one third less potent than fentanyl, has an extremely short duration of action but tends to accumulate when large doses are used over prolonged periods. Since its recent release, alfentanil has become the preferred method for providing analgesia for short painful procedures (eg, fracture reduction) in many centers. Doses of 10 to 25 µ-g/kg usually produce adequate analgesia, and children are often ready for discharge sooner than when other agents are used.
All opioid agents have similar side effect profiles, the most important of which in the acute setting is respiratory depression. A unique feature of fentanyl and its analogues is the potential for the development of chest wall rigidity and concomitant impaired ventilation, although these effects usually are observed after large doses are administered rapidly. Other common side effects of opioids include pruritis, nausea, vomiting, and urinary retention.
In a relatively short period of time, the short-acting benzodiazepine midazolam (Versed, Roche Laboratories, Nutley, New Jersey) has become the most frequently used preoperative sedative in children. Like many other agents commonly used in children, the Food and Drug Administration has not, however, approved pediatrie indications. Hie main attributes of midazolam are the provision of potent anxiolysis and anterograde amnesia, combined with a favorable overall safety profile. Its onset and duration of action are predictably short, and since it is water soluble, there is no pain on injection. Midazolam may be administered by oral, nasal, or IV routes in doses of 0.5, 0.3, and 0.05 mg/kg, respectively. Oral doses of up to 0.7 mg/kg have been shown to be efficacious without significant side effects.7"10 Its use is limited, however, because it lacks analgesic properties, and in appropriate doses, it does not reliably produce a cooperative, motionless child. Thus, midazolam is unsuitable as the sole agent in cases in which a child needs to be motionless or for procedures that involve painful stimuli. Midazolam is, however, an effective sedative for painful procedures when it is combined with an analgesic such as ketamine or fentanyl, although the risks of respiratory depression increase.1 li12 Concomitant erythromycin therapy may significantly prolong its duration of action.13
Nitrous oxide has been used in pediatric dentistry for more than a century with an excellent safety record. In concentrations of less than 50%, nitrous oxide is not an anesthetic in the true sense of the word, but provides mild sedation, anxiolysis, and analgesia. A prospective investigation compared 30% nitrous oxide with placebo (100% oxygen) for use as a sedative during laceration repair in 34 children.14 Although nitrous oxide was effective in reducing pain scores in all children, it was most effective in those older than 8 years.
Concern about the safety of medical personnel has limited its more widespread use in hospital settings. Chronic exposure inactivates the vitamin B(2 component of the enzyme methionine synthase, which is essential for folate metabolism, and in addition, teratogenic effects have been observed in laboratory animals after prolonged exposure. Although there is no direct evidence that nitrous oxide has teratogenic effects in humans, a controversial study recently reported a higher-than-normal incidence of spontaneous abortions among women working in dental offices.15
Nitrous oxide should be used only in conjunction with a functional scavenging system, and environmental levels should not exceed the National Institute for Occupational Safety and Health's recommendations (25 ppm). Because of these limitations and the cost involved with implementing nitrous oxide sedation, few institutions use it on a regular basis outside surgical and dental suites. In addition, because safety data are lacking, the AAP recommends that nitrous oxide not be used in combination with other sedatives in the dental setting.2
Ketamine is a dissociative anesthetic that is structurally related to phencyclidine (PCP), a common drug of abuse. It is unique in that it is one of the few agents available that in low doses is both sedative and analgesic, and in high doses produces total anesthesia. Low-dose ketamine produces sedation, anxiolysis, analgesia, and anterograde amnesia, with little risk of respiratory depression. Its disadvantages include increased oral secretions and the possibility of adverse psychologic phenomena such as hallucinations. The latter problem may be attenuated by the concomitant use of a benzodiazepine.
In a large prospective series,16 4 mg/kg of intramuscular ketamine was used to sedate 108 children during a variety of painful procedures in the emergency ward. Acceptable sedation was attained in 97% of children after a single injection, and although one child experienced vomiting accompanied by transient laryngospasm and cyanosis, overall the technique was reliable and safe. The reliability of intramuscularly administered ketamine often makes it the drug of choice for sedating developmentally disabled patients in whom starting an intravenous line would be otherwise problematic.
Propofol (Diprivan, Stuart Pharmaceuticals, Wilmington, Delaware) is a nonbarbiturate hypnotic agent that only recently became available in the United States. It has been used extensively in Europe as a sedative in the intensive care setting and is now commonly used to induce and maintain general anesthesia and as a sedative for painful medical procedures or when a motionlessness child is required (eg, during MRI). The IV form of propofol is dissolved in an aqueous solution of 10% soybean oil, 2.25% glycerol, and 1.2% purified egg phosphatide. As a result of its formulation, propofol is contraind in patients who are allergic to egg products. The dose is titrated to effect, usually in increments of 0.5 to 1 mg/kg.
The major advantage of propofol over other hypnotic agents is its extremely short duration of action and an apparent absence of accumulation after even prolonged exposure. Its onset and duration of action are easily controlled, and patients typically return rapidly and completely to baseline mental status soon after administration is discontinued. In higher doses, propofol may cause respiratory depression and in susceptible patients, cardiac depression. Pain and burning at the site of injection can be attenuated by the addition of 0.5 mg/kg of lidocaine.
We have used IV propofol in children undergoing bone marrow aspiration and lumbar punctures in the outpatient oncology clinic. Typically, doses of up to 15 mg/kg are required over a half-hour period. Treated children are deeply sedated and breathe spontaneously with "blow-by" oxygen administered continuously. No complications or episodes of oxygen desaturation have been observed in more than 1 year of use.
For decades, investigators have attempted to formulate a compound that would provide effective dermal analgesia upon contact with the skin. In 1980, a pilot study showed the effectiveness and lack of significant side effects of EMLA Cream (Astra USA Ine, Westboro, Massachusetts), a eutectic mixture of local anesthetics that contains 2.5% lidocaine and 2.5% prilocaine.17 When mixed in equal amounts, the pure solid bases of lidocaine and prilocaine form a eutectic mixture (oil at room temperature). EMLA Cream is an oil-in-water emulsion of these two bases that allows effective tissue penetration at low total drug concentrations.
To be effective, EMLA Cream is applied generously on the dermal surface to be anesthetized and is covered with an airtight occlusive dressing for at least 45 minutes. Thus, EMLA Cream is not suited for use in unanticipated procedures such as ventpuncture in the emergency ward. Rather, patients undergoing elective procedures may benefit from the application of EMLA Cream while still on the hospital ward or just prior to leaving home for the hospital or clinic.
In 1982, investigators showed that EMLA Cream was superior to placebo in preventing the pain of IV cannuiation in children.18 EMLA Cream also has been shown to eliminate or decrease pain associated with lumbar punctures and injections into subcutaneous reservoirs in children with cancer.19,20
Not all reports on the use of EMLA Cream in children have been favorable. In 1988, a report from the Children's Hospital National Medical Center compared EMLA Cream with intradermal lidocaine infiltration in 42 children aged 7 to 12 years.21 The anesthesiologist performing the procedure, an independent observer, and the child, assessed response to a skin "nick" with a 19-ga needle or IV cannuiation with a 20-ga catheter. In addition to finding similar pain scores between the EMLA Cream and lidocaine groups, the authors found no correlation between the level of cooperation and lower pain scores. They also noted that after removal of the EMLA Cream, the skin retained a greasy quality that made securing the IV catheter difficult. Studies such as this emphasize that the interpretation of pain in pediatrie patients is made difficult by imperfect measuring devices. Even though the area of puncture is anesthetized, the anxiety and fear of the injection can cause considerable distress that may be interpreted by an observer, as pain.
Side effects of" EMLA Cream are transient and minor, and consist of localized itching, pallor, or erythema. Some authors have suggested that a slight blanching of the skin is a useful marker for complete anesthesia and will persist for 1 to 2 hours.17 In certain situations, however, EMLA Cream can be hazardous. Young infants are particularly susceptible to prilocaine -induced methemoglobinemia because of their diminished levels of erythrocyte methemoglobin reduciase.22 Therefore, EMLA Cream is contraindicated in infants younger than 1 month old.
Practitioners have investigated nonpharmacologic means of helping children cope with painful procedures in order to avoid the risks and costs associated with pharmacosedation. Such approaches include cognitive-behavioral coping strategies, hypnosis, and parental assistance. Because they involve cooperation and skill, these techniques are difficult to use in the acute care setting and generally are considered most useful in children who have chronic pain or who must undergo multiple painful procedures (eg, cancer and burn patients). A recent critical analysis of these techniques can be found elsewhere.23
Pediatricians and pediatrie subspecialists are usually primarily responsible for the care of children undergoing medical procedures and can play an important role in ensuring humane and pain-free treatment. As the focus on providing comfort in these settings increases, the question arises as to who should be primarily responsible for the safe administration of conscious and deep sedation in children. Anesthesiologists are most familiar with the drugs commonly used for sedation and with techniques for protecting the airway but cannot always be available to oversee or participate in the sedation of children outside the operating room. Pediatricians, while often skilled and knowledgeable in the administration and safety of sedative agents, may have limited access to agents such as ketamine or propofol. The American Society of Anesthesiologists concurs with the Joint Commission on Accreditation of Healthcare Organizations in recommending that the director of the anesthesiology department "participate. . . with the representatives of other departments/services that provide anesthesia services in the formulation of mechanisms and material that help to provide uniform quality of anesthesia services throughout the hospital." Although anesthesiology departments are not required to be responsible for sedation performed by other practitioners, they are responsible for assisting in the creation and impiemention of policies and safety guidelines.21* Close collaboration between pediatricians and anesthesiologists in this setting can result in improved outcomes and enhanced patient satisfaction.
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