Pediatric Postoperative Pain Management

\ Acute Pain in Children

0031-3955/89 $0.00

+

.20

Pediatric Postoperative Pain Management

Charles B. Berde, MD, PhD*

Children and adolescents frequently undergo surgery, and often they experience pain postoperatively. 29. 63 Epidemiologic studies suggest that children frequently receive inadequate treatment for postoperative pain. 13. 83.84 They are often prescribed smaller doses (on a "per kg" basis) at longer intervals than adults. When doses are prescribed "pm," the smallest doses in the prescribed range are often chosen. 61 There are no data to support the view that the child's pain threshold is higher than the adult's or that the immediate experience of postoperative pain is any less intense. 2 The inadequate treatment of postoperative pain is particularly unfortunate because, for the overwhelming majority of children, analgesia could be provided with ease and with a very wide margin of safety. 3

PATIENT EVALUATION

Problems related to pain assessment are discussed elsewhere. 47. 67. 68 As with all patients, postoperative patients require assessment of the intensity, location, and character of their pain, as well as an appreciation for the entire spectrum of factors that modulate the experience. In approaching a child with postoperative pain, it remains important to make an assessment and diagnosis. For example, a child who has undergone cystoscopy may quite naturally complain of burning urethral pain. Conversely, crampy upper abdominal pain is not expected in this setting and may reflect bladder perforation. Similarly, in a child who has undergone a lateral thoracotomy, shoulder pain might be referred pain from the diaphragm or may reflect awkward intraoperative positioning of the nondependent arm. As with patients with any sort of pain, the experience of postoperative pain can be modified by fear, anxiety, depression, and a number of other factors. 5 The behavioral manifestations of pain vary with age and clinical

*Assistant Professor of Anesthesia,

Harvard Medical School; Director, Pain Treatment Service; Associate in Anesthesia, Children's Hospital, Boston, Massachusetts

Pediatric Clinics of North America-Vol. 36, No.4, August 1989

921

922

CHARLES B. BERDE

condition. It is frequently difficult to decide to what extent an infant or toddler who has undergone surgery is crying from pain or from fear, anxiety, or loneliness. Often, in practice, a therapeutic trial of reassurance or cuddling is performed, and responses are used to judge pain intensity. Many infants and younger children react to pain by withdrawing from their environment. Stated another way, children may lie still in bed not because they are comfortable but because they hurt too much to move or they are afraid to move. At times, provision of adequate analgesia to these children will increase, not decrease, their level of activity.

MANAGEMENT APPROACH Nonpharmacologic Modalities The management of postoperative pain begins preoperatively with appropriate preoperative teaching and guidance. 28, 81 Most children benefit from a simple and honest explanation of what they can expect following surgery. If surgery is expected to be painful, it is best to explain that there will be some hurting, but that it will go away after a while, and there will be some medicine to make it hurt less. The simple assertion that postoperative pain will go away after several days is helpful. Younger children have a protracted sense of time relative to adults, and unless someone tells them that the pain will go away after a while they may surmise that their pain will go on forever. The use of behavioral and cognitive techniques for alleviation of distress postoperatively should be encouraged. Guided imagery, hypnosis, art and activity therapies, and distraction are extremely useful for children of diverse ages. 33. 62. 97 Physical modalities, including transcutaneous electrical nerve stimulation,56. 90 may have a role in postoperative analgesia, although they are unlikely to replace pharmacologic measures in the majority of cases. Premedication Premedication before surgery can help to alleviate fear and make anesthetic induction less stormy. In the overwhelming majority of cases, there is simply no reason to employ intramuscular injections; an oral premedication is safe and effective and can be given even to outpatient surgery patients without delaying discharge. 2o , 91 An oral elixir combining an opioid with a benzodiazepine or other sedative-hypnotic is convenient and effective. For example, a series of studies at the Children's Hospital of Philadelphia has shown the efficacy of oral administration of either morphine or meperidine in combination with either diazepam or pentobarbital. 20. 91 The synergism of the two classes is useful in this setting and diminishes the likelihood of dysphoric reactions seen in some children given a sedativehypnotic alone. It should be given a minimum of 1 hour preoperatively for maximum benefit. There is a suggestion based on adult work that addition of an opioid as premedication may diminish postoperative analgesic requirements (pain is more readily prevented than treated). 71, 89

\ PEDIATRIC POSTOPERATIVE PAIN MANAGEMENT

923

Anesthetic Induction and Management An atraumatic method of anesthetic induction should be encouraged in order to diminish the fear and anxiety associated with the operative experience. 25. 75 Whenever feasible, parental presence at induction or preinduction should be encouraged. Ideally, maintenance of anesthesia should proceed with a coordinated plan for postoperative analgesic management. If systemic opioids are going to be used postoperatively, then it is often convenient and natural to employ an opioid-based anesthetic technique. Conversely, if it is likely that a regional block will provide prolonged and complete analgesia postoperatively (for example, a wrist block for hand surgery, see later), then it may make sense to avoid opioids intraoperatively in order to diminish the likelihood of side effects such as nausea. For certain children, anesthetic considerations unrelated to postoperative analgesia dictate the choice of agents; nevertheless, in the great majority of otherwise healthy children scheduled for painful surgery, postoperative analgesic considerations should playa greater role in the plan for anesthetic management.

4:

PHARMACOLOGIC MANAGEMENT78 Nonopioid Analgesics Mild to moderate forms of postoperative pain may benefit greatly from administration of acetaminophen or nonsteroidal anti-inflammatory agents (NSAIDs). Even more severe forms of pain that require opioid medications are helped by administration of these agents, because they provide additive analgesia without increasing dose-related opioid side effects such as respiratory depression, urinary retention, or sedation. Acetaminophen has an extremely high therapeutic ratio and few contraindications. 82 It does not cause gastritis or bleeding. In postoperative patients, it is rare that acetaminophen's suppression of fever will obscure recognition of an infection. It can be given at any age (including prematures) in doses of 10 to 15 mg per kg PO or 15 to 20 mg per kg PR q4h. For postoperative patients, particularly those undergoing ambulatory surgery, it is especially convenient to administer the first dose by rectal suppository prior to emergence from anesthesia, although absorption is erratic. 34 Several of the NSAIDs have been shown to provide excellent postoperative pain relief in adults. Most can cause gastritis and prolong the bleeding time, although several adult studies suggest that these are not problems with short-term perioperative use. Maunuksela et al64 have shown that intravenous administration of indomethacin is effective as an analgesic for children postoperatively, although it does not eliminate the need for opioids in operations associated with severe pain. In their studies, bleeding and gastritis were not found to occur. No intravenous preparations of NSAIDs are currently available in the United States for postoperative use. Oral administration of ibuprofen (8 mg per kg per dose PO q6h) or naprosyn (5 mg per kg per dose bid or tid) beginning 1 to 2 days postoperatively is

924

CHARLES B. BERDE

reasonable for older children and adolescents undergoing nongastrointestinal procedures who do not have specific contraindications. For children age 2 to 12 years, the approved NSAIDs in the United States are Naprosyn and tolmetin. 87 Rectal suppositories of indomethacin are available and afford a convenient route of administration for patients unable to take oral analgesics postoperatively. Currently available nonopioid analgesics all have ceiling effects. (For example, 2 g acetaminophen produces no more intense analgesia than 1 g.) Current investigations are examining newer NSAIDs with higher ceiling effects, as well as agents that act on other peripheral mediators of inflammation and nociception.

Opioid Analgesics (Narcotics) Opioids 15,95 form the mainstay of postoperative analgesic management. They are both the most commonly used and most commonly misused and misunderstood agents for analgesia. 76 For the vast majority of children undergoing surgery, opioids produce excellent analgesia with a wide margin of safety. Detailed treatments of opioid pharmacology in children are provided elsewhere in this volume and in other reviews. 94 There is marked individual variation in opioid dose requirements, and doses should be adjusted based on clinical signs. Suggested starting doses are given in Table 1. The primary problem in administering opioids for postoperative pain is usually no more complicated than finding and maintaining a plasma concentration (or brain concentration) than lies above the effective analgesic threshold and below levels which cause coma or respiratory depression (Fig. 1). In most patients, such a "window" is reasonably wide; nevertheless, Table 1. Starting Doses for Postoperative Analgesia with Opioids ROUTE

Continuous IV

Intermittent IVt

Oral Intramuscular

DRUG DOSE

morphine meperidine fentanyl morphine meperidine methadone:j: codeine morphine methadone:j: morphine meperidine

(AGE> 3 MONTHS)'

0.05--0.06 mglkg/hr 0.5--0.6 mg/kg/hr 2-4 J.l.g/kg/hr 0.08-0.1 mg/kg q2h 0,8-1 mg/kg q2h Loading: 0.1 mglkg q2h x 2 Maintainence: 0.04-0.09 mg/kg q4-8h 0.5--1 mg/kg q4h 0.3 mglkg q4h 0.1-0.15 mglkg q4-8h 0.1-0.15 mglkg q3-4h 1-1.5 mg/kg q3-4h

*For nonintubated patients in the first 3 months of life, or for other patients with an increased tendency for respiratory depression, starting doses should be diminished by at least a factor of 3 to 4 from the doses recommended here, and facilities for intensive observation and respiratory support should be available. tIn most circumstances, intravenous boluses should be administered slowly, e.g., over 15 to 20 minutes. :j:A more detailed loading schedule and sliding scale is suggested in the text. If somnolence occurs, dose should be diminished immediately and the interval may be extended greatly: often q8-12h dosing becomes adequate.

I

PEDIATRIC POSTOPERATIVE PAIN MANAGEMENT

925

Dose-Response Effects of Norcot i cs Como Figure 1. The graph depicts the effects associated with increasing plasma opioid levels. The shaded area depicts the "analgesic window" between the extremes of excessive sedation and inadequate analgesia.

An 0 1g es i 0 Po 1n

Increosing Narcotic Plosmo level s in daily clinical practice it is common for bolus dosing to generate a cycle of pain alternating with comfort or sedation (Fig. 2). This pattern is unfortunate, because it exposes patients to the toxicities of opioids while providing only intermittent benefits. It is unnecessary and harmful to make patients experience severe pain 1 hour out of every 4 hours. 3, 61 In a small number of patients, no such therapeutic window exists, or the window is so narrow that it is difficult to find in clinical practice. This is particularly true of the respiratory depressant effects of opioids in premature newborns with a tendency toward apnea,42, 55 in end-stage cystic fibrosis, or in patients with compromised airways, (for example, following a pharyngeal flap operation). In these cases, opioids should be used for postoperative analgesia with extreme caution, and only in a circumstance that permits intensive observation and immediate availability of respiratory support. For intubated neonates postoperatively, these concerns are less important, and opioids should be prescribed as needed. Preliminary studies suggest that by 3 to 6 months of age, healthy infants have no greater respiratory depression from opioids than adults. 45 Newborns have variable decreases in opioid clearance. 40, 49, 53, 59, 50, 86 . Opioids can be administered by a number of routes, including intravenous, subcutaneous, oral, sublingual, nasal, rectal, and transdermal. 46 Although intramuscular boluses result in less dramatic peaks and valleys than intravenous boluses, intramuscular injections should be condemned because they are so distressing to patients. Surveys suggest that children frequently will deny that they have pain in order to avoid injections, and they often find the distress of shots as bad as any aspect of the perioperative experience. 29 When administered on a prn basis every 3 to 4 hours, inevitably there is a return of severe pain prior to the next shot, creating a pain cycle. Oral administration of opioids should be encouraged when patients are taking oral fluids and food, but frequently it cannot be relied on in the immediate postoperative period due to nausea or ileus. Parenteral administration should be used until fluids are tolerated on a consistent basis. Almost all children undergoing painful surgery have an intravenous line postoperatively, and the intravenous route offers the advantages of complete bioavailability, immediate effect, and lack of discomfort with administration.

926

CHARLES B. BERDE

Intramuscular Administration of Narcotics

Narcoti c Admi ni strati on by Intrayenous Boluses Coma

Coma

Analgesia

Analgesia

Pain

Pain

2 3 4 time (hours)

A

o B

Narcotic Rdministration by Continuous Infusion

2 3 4 time (hours)

Intrayenous Admi ni stration of Methadone by Loading Dose and Small Supplemental Boluses

Coma Analgesia Coma Pain

o

c

2

4 6 B time (hours)

Patient-Controlled Analgesia

Anal gesi a

t-~:-------=----l

Pain

o

o

2 4 6 8 time (hours)

Coma Analgesia Pain

o E

2 3 4 time (hours)

Figure 2. Each of the panels depicts the typical course of a patient receiving analgesia via each of these regimens. A, Intravenous boluses of intermediate duration opioids (e.g., morphine, meperidine) result in dramatic fluctuations in plasma levels and in clinical effects when given at 4-hour intervals. B, Intramuscular injections of morphine or meperidine also produce fluctuations in effect, although somewhat less severe than seen with intravenous boluses. C, Continuous infusions of opioids can produce a constant clinical effect that remains between the extremes of inadequate analgesia and sedation. Skilled assessment is required to prevent a slowly rising plasma level that could produce sedation later. D, Intravenous administration of methadone by initial loading followed by small supplemental boluses every 4 to 6 hours can proVide relatively constant analgesia similar to that achieved with a continuous infusion. E, Administration of opioids by patient-controlled analgesia (PCA) can result in a constant analgesic effect, with excellent patient satisfaction.

PEDIATRIC POSTOPERATIVE PAIN MANAGEMENT

927

Although intravenous boluses of intermediate duration opioids (morphine, meperidine) can be effective, they result in a greater peak effect and shorter duration of analgesia than intramuscular injection of comparable doses (see Fig. 2). For the most commonly used agents, (morphine, meperidine, and fentanyl) intravenous boluses need to be given at intervals of no more than 2 hours to avoid a pain cycle. Frequent administration of these agents may be inconvenient for a busy nursing staff, and often there are delays, with associated pain cycles. In general, intravenous boluses of any opioid should be dripped slowly, for example over 20 minutes. A more constant effect can be achieved with a continuous intravenous opioid infusion. 16, 53, 74 Titration to clinical effect permits avoidance of either severe pain or severe somnolence and respiratory depression. Hospitals that use this approach regularly for routine postoperative pain (such as the Hospital for Sick Children at Great Ormand Street in London) report very good success with it and minimal problems (D. Sumner, personal communication). Starting morphine infusion rates for opioid-naive subjects average roughly 0.04 to 0.06 mg per kg per hr for children age 3 months and older, although there is marked individual variation in the doses required. N on intubated newborns and infants in the first 2 to 3 months of life should probably be started at much lower infusion rates, for example, 0.015 mg per kg per hrS l , 56, 60 and only in a setting that permits very close observation and immediate availability of individuals skilled at airway management. An infusion pump is required. Although this method is generally quite safe, it does require some skill in patient assessment in order to avoid a slowly rising plasma level with delayed somnolence and respiratory depression (Fig. 2). The major barriers to use of continuous infusions are lack of familiarity with the technique and the unfounded belief that morphine infusions should be reserved for the terminally ill. The requirement for an infusion pump and continuous access to a venous port can be inconvenient in some cases, particularly in the case of critically ill children receiving multiple medications through a limited number of venous ports. For patients without coagulopathy or severe hypoperfusion, a conven" ient alternative that avoids the need for constant access to an intravenous port is the use of a continuous subcutaneous opioid ihfusion. 73 A 25 gauge butterfly needle or a 22 to 24 gauge intravenous cannula is placed subcutaneously on a flat skin surface on the thorax, abdomen, or thigh and covered with a sterile transparent dressing. Once the needle or catheter is placed, it is usually not uncomfortable, and it is tolerated well. An infusion pump is used to deliver a concentrated solution of opioid (usually morphine at 10 to 50 mg per cc) at rates of no more than 1 cc per hour. In a steady state, dose requirements are similar to those with continous intravenous infusion. Patient-controlled analgesia (PCA) is a method of drug delivery that employs a computer-controlled infusion pump that permits the patient to administer a small bolus dose by pressing a button (Fig. 3).7,39 Administration of a dose activates a "lock-out" mechanism so that the patient cannot repeat the dose before a specified period of time, usually 8 to 15 minutes. In addition, there is usually a cumulative maximum dose permitted over a

928

CHARLES B. BERDE

Figure 3. A patient administering morphine via a PCA pump. The technique permits individual titration and a relatively constant analgesic effect.

longer period, generally 3 to 4 hours. In this way, the patient is permitted some flexibility and a sense of control, yet overdosage is avoided. Extensive studies in adults have shown that patients are extremel) satisfied with this method of analgesia. They generally do not medicate themselves heavily and tend to prefer a moderate dosing regimen that results in mild to moderate pain and relatively few side effects. 6 In short, patients will choose to experience some pain in exchange for fewer side effects and for a sense that if they felt severe pain, they could give themselves medication immediately. A number of pumps are available on the market with different "user-friendly features." Design modifications make these pumps extremely safe for routine use. Recent studies have suggested that PCA is quite applicable for adolescents. 19, 24, 72 The youngest age for routine use is currently under intensive study, and recommendations at this time are provisionaL In some pediatric centers, the technique has been used routinely in 6 years olds and younger in selected cases. Other more cautious centers have restricted its use to children age 11 years and older (D. Tyler, L. Broadman, D. Cohen; personal communications). It is helpful to administer bolus doses prior to beginning the pump, since the lock-out feature makes it difficult to "catchup" with severe pain. Key to a successful PCA program is adequate patient, parent, and nursing instruction prior to use. The patient is usually the best judge of the need for dosing, and problems have been reported with parental interference with dosing. A slight continuous "background" infusion may be helpful in circumstances of severe pain, particularly at night-

PEDIATRIC POSTOPERATIVE PAIN MANAGEMENT

929

time, to avoid the need for "catch-up" on awakening. Some of the newer machines permit this background infusion as well as PCA using a single pump. Contraindications include inability to push the button (due to weakness or immobilization), inability to understand the connection between dosing and obtaining relief, and a patient's wish not to be bothered with responsibility for providing analgesia. In these cases, continuous opioid infusions may be preferable to PCA. A convenient alternative to continuous opioid infusions is the use of a very long-acting opioid, methadone, by intermittent intravenous boluses. 8, 11,38 Methadone is a synthetic opioid whose elimination half-life in children averages roughly 19 hours,11 more than six times as long as morphine. Following initial loading (0.2 mg per kg at the beginning of a nitrous oxideopioid relaxant anesthetic, titration of increments of 0.05 mg per kg every 10 minutes until comfort is achieved in the recovery room, or 0.1 mg per kg IV q2-3 h times 3 in awake opioid-naive patients), it can be administered in small increments intravenously over 20 min every 4 hours via a "sliding scale" on a "reverse prn"3,8 (nurse asks the patient) basis: 0.07 to 0.08 mg per kg for severe pain; 0.05 to 0.06 mg per kg for moderate pain; 0.03 mg per kg for little or no pain, if the patient is alert; and no drug if the patient has little pain and is somnolent. This technique affords the constant effect of a continuous infusion, with the follOwing convenient features: (1) Since continuous access to an intravenous port is not required, this method is particularly useful for patients who require multiple medications or blood products with a limited number of venous access ports. (2) An infusion pump is not required. (3) The time of peak effect and peak respiratory depression is soon after the bolus, so that the risk of delayed respiratory depression may be less than that for continuous infusions. To date, more than 240 children and adolescents undergoing surgery have received methadone in our hospital according to the above algorithm. It is important to reduce dosages and extend the dosing interval immediately if somnolence ensues. Theoretically, if overdosage were to occur, it might be necessary to continue naloxone administration for an extended period of time, In general, opioids are more similar than they are different, and there are very few clinically important differences in the available opioids for pediatric use with regard to their respiratory depression or other side effects at equianalgesic doses. 15 Clinicians converting from one opioid to another should be aware of potency ratios and oral bioavailability.78 For continuous intravenous use, or for intramuscular or subcutaneous use, it makes sense to choose morphine as the routine agent in most circumstances. Morphine is inexpensive, readily available, and has received extensive study in pediatrics. 22, 53, 59, 60 There is reason to avoid prolonged use of meperidine, since a metabolite of meperidine has been associated with convulsions and since the incidence of dysphoria increases with prolonged use. 36 Choice of oral opioid analgesics has been governed largely by custom. For mild to moderate postoperative pain codeine is used most commonly. It is recommended at doses of 0.5 to 1 mg per kg PO q4h. Convenient features of codeine include: (1) it is readily available in an elixir form or in combination with acetaminophen, (2) the combination preparation with

930

CHARLES B. BERDE

acetaminophen is not treated by the Drug Enforcement Administration as a Schedule III controlled substance, and (3) it has relatively little stigma limiting its prescribing in outpatients. More severe postoperative pain is often treated with oral administration of meperidine or a combination of oxycodone and acetaminophen (Percocet). An oral elixir or morphine has been shown to provide excellent analgesia for children following orthopedic surgery.77 In this clinical trial, a oral morphine elixir provided better analgesia than intramuscular meperidine. Methadone is well absorbed orally and convenient because of its prolonged action.

REGIONAL BLOCKADE

Regional blockade85 consists of the application of medications locally to modulate or block transmission of afferent nociceptive impulses. The two classes of agents used most often are local anesthetics and opioids. Certain forms of regional blockade, such as wound infiltration or digital blocks, may be performed by the pediatrician or pediatric surgeon, while others, such as epidural blockade, should be performed only by anesthesiologists. Nevertheless, an understanding of the effects of major forms of regional blockade may be helpful to the pediatrician, because they are being used with increasing prevalence for pediatric patients worldwide. Local anesthetics are classically thought to act by blockade of sodium channels and thereby inhibiting the propagation of the action potential, but they appear to have other actions as well. 93 Table 2 lists but they appear to have other actions as well. 93 Table 2 lists some of the routes of administration with applications. For postoperative use, the most commonly used agents are bupivacaine (Marcaine, Sensorcaine) and lidocaine (Xylocaine). The advantages of bupivacaine are a prolonged duration of action and, in dilute Table 2. Regional Blockade TYPE OF BLOCK

Wound infiltration Wrist Penile (dorsal or ring) Ilioinguinal/iliohypogastric Axillary Femoral Intercostal Interpleural Caudal epidural local anesthetic opioids Lumbar epidural local anesthetic opioids Thoracic epidural local anesthetic and opioids

APPLICATION

Vascular cutdown, suture oflaceration Syndactyly repair Circumcision, hypospadius repair Inguinal hernia repair Colles' fracture Midshaft femur fracture Lateral thoracotomy Lateral thoracotomy, nephrectomy Complex hypospadius repair with bladder graft Club foot repair Ureteral reimplantation Urologic reconstruction Hemipelvectomy Thoracotomy Thoracic or abdominal surgery in patients with severe lung disease

PEDIATRIC POSTOPERATIVE PAIN MANAGEMENT

931

concentrations, a relative preference for sensory blockage over motor blockade. Lidocaine is preferred over bupivacaine for test dosing. Most children prefer to be asleep during surgery and request general anesthesia. Nevertheless, use of regional blockade can be an excellent adjunct to intraoperative management and can provide outstanding postoperative analgesia. When performed at the beginning of surgery after induction of anesthesia, it may lead to reduced anesthetic requirements and more rapid emergence. Numerous adult studies have shown that for a variety offorms of major surgery, regional anesthesia and analgesia provide superior attenuation of stress responses and a quality of postoperative analgesia that can be attained by systemic opioids only at the price of greater degrees of opioid-associated \ide effects, such as nausea, respiratory depression, and sedation. 21 . 51 In adults undergoing major thoracoabdominal and vascular surgery, several series suggest reductions in perioperative morbidity21, 41 and even mortality96 associated with regional analgesia postoperatively. Pediatric series comparing systemic and regional analgesia have shown superior analgesia and fewer side effects, such as nausea, sedation, or hypoventilation, in patients receiving blockade 14, 54, 58, 66, 88 in comparison with systemic opioids. Peripheral nerve blockade and wound infiltration are extremely effective and simple adjuncts for providing postoperative analgesia. As listed in Table 2, these blocks are useful for a number of forms of peripheral surgery. 12, 43 For example, ring block30 or dorsal nerve block of the penis is extremely simple, safe, and effective in providing analgesia for roughly 8 to 20 hours following circumcision and simple hypospadius repair. 23, 37, 52, 65, 92 When performing infiltration (or any regional block technique), concern for avoiding toxic doses of local anesthetic is important, especially in newborns and younger infants. Dilute solutions of local anesthetic permit use of larger volumes for the same number of milligrams administered. For example, when performing a chest tube insertion in a 2 kg neonate, safe doses of lidocaine would be 2 cc of an 0.5 per cent solution (5 mg per cc; 5 mg per kg; 10 mg total dose) but only 1 cc of a 1 per cent solution or 0.5 cc of a 2 per cent solution. More concentrated solutions can be diluted with preservative-free normal saline to the desired concentration. Excessive plasma levels may be caused by inadvertent intravascular injection or by correct needle placement with excessive volumes injected and subsequent systemic uptake. Toxic reactions include convulsions and profound myocardial depression or dysrhythmia. Warning signs include tinnitus, headache, blurry vision, metallic taste, and lethargy. Treatment consists of ensuring a patent airway and adequate ventilation, circulatory support, and treatment of convulsions with benzodiazepines or short-acting barbiturates. Vasodilation due to excessive sympathetic blockade is best treated with alphaadrenergic vasopressors (phenylephrine, ephedrine) in addition to fluids. 85 Epinephrine-containing solutions are to be encouraged in highly vascular areas (for example, intercostal blocks) in order to limit systemic absorption and prolong duration; they are to be avoided in situations in which they might lead to ischemic injury (for example, penile and digital blocks). Topical administration of local anesthetics on operative incisions (for example, local anesthetic cream for circumcision88) is a simple and

932

CHARLES B. BERDE

promIsmg technique that deserves further study, especially regarding plasma levels achieved in younger infants. Regional blockade is particularly important in those circumstances in which there are relative contraindications to systemic opioid administration. For example, the most common operation in the preterm newborn is inguinal hernia repair. The premature newborn has a propensity for lifethreatening apnea following general anesthesia,42, 55 and it is reasonable to assume that this tendency would be exacerbated by the administration of opioids. Use of spinal anesthesia by experienced practitioners for hernia repair in preterm newborns who are less than 44 to 52 weeks' postconception at the time of surgery may diminish the risk of apnea. 1 Use of ilioinguinal and iliohypogastric nerve blocks at the termination of surgery permits a prolonged period of greater comfort without use of opioids. Local anesthetic blockade can also be accomplished at the level of the brachial31 or lumbar plexus,43 resulting in analgesia lasting 6 to 18 hours with bupivacaine solutions. Performance of these blocks in children requires some special expertise and appreciation for the effects of these blocks on subsequent sensory and motor examination. Epidural analgesia is probably the most versatile regional analgesic technique. It consists of application of medications in the potential space lying superficial to the dura mater and deep to the ligamentum flavum (Fig. 4). Medications can be administered either by a single injection or repeatedly via a catheter placed through a needle. The epidural space can be approached at any level,27 but for most children, it is approached either at lumbar levels 27, 35 or via the caudal approach17, 54, 58, 66, 80; the latter approach is extremely convenient and effective in younger infants (see Fig. 4). Numerous studies have confirmed the safety and efficacy of caudal blockade with bupivacaine for analgesia following any form of surgery below the umbilicus. 17 Single-shot caudal blockade with bupivacaine is associated with an extremely low incidence of urinary retention and therefore is regarded by many as an acceptable technique, even for outpatients. For selected patients, epidural analgesia can be maintained postoperatively by a continuous infusion of bupivacaine, particularly in patients whose surgical result benefits from postoperative immobilization and/or some regional sympathetic blockade. When very dilute solutions ofbupivacaine are used for continuous infusion (for example, 0.1 to 0.125 per cent,32, 57 it is generally possible to achieve complete analgesia with very little weakness. The choice of epidural administration of local anesthetics versus opioids depends on a number of factors that will be outlined in examples below. Interpleural administration of local anesthetics is a new and promising route of administration for patients undergoing lateral thoracotomy or major unilateral upper abdominal or retroperitoneal surgery79; McIlvaine has reported on extensive use of this technique in children. 69, 70 Information is evolving rapidly regarding technical considerations that influence the success of the technique, and practitioners are urged to consult with experts prior to use of this technique. At present, it is my view that epidural analgesia remains a more predictable and versatile technique in experienced hands for children undergoing major unilateral thoracoabdominal surgery.

PEDIATRIC POSTOPERATIVE PAIN MANAGEMENT

933

\

-Figure 4. A, The anatomy of the lumbar epidural space is shown to illustrate the technique of lumbar epidural blockade. B, The anatomy of the sacral hiatus is shown to illustrate the technique of caudal epidural blockade.

As more data become available, interpleural analgesia may become a practical alternative, particularly because of its ease in catheter placement. Opioids can also be administered regionally. Application of opioids in the epidural or subarachnoid space results in activation of opioid receptors in the dorsal horn of the spinal cord to produce regional analgesia without anesthesia, that is, segmental effects on pain perception without either sensory blockade (numbness), motor blockade (weakness), or sympathetic blockade (vasodilation). Studies in adults and children postoperatively have shown that epidural or subarachnoid administration of opioids can provide outstanding analgesia of prolonged duration. 18. 26. 35, 48, 50, 54, 80. 96 The segmental effects of epidural and subarachnoid opioids and their duration of action differ according to their physicochemical properties.

934

CHARLES B. BERDE

Morphine spreads rostrally to a considerable extent. Thus, lumbar or even caudal epidural administration of morphine has been shown to be effective for pain arising from thoracic dermatomes. 80 For routine postoperative use, we generally prefer epidural to subarachnoid administration. Brown and Broadman 19 and others have administered a single-shot subarachnoid injection of morphine under direct vision through the operative field via a 26gauge needle in patients undergoing posterior spinal fusion and instrumentation for scoliosis. This injection can provide complete analgesia typically for 14 to 28 hours following this very painful operation. Properly employed, epidural and subarachnoid administration of opioids can produce a greater degree of analgesia with less respiratory depression than comparable optimal administration of systemic opioids. Nevertheless, rostral spread of morphine in the cerebrospinal fluid following epidural or subarachnoid administration can produce delayed respiratory depression. This is seen particularly in elderly adults who have also received systemic opioids; the incidence has been dramatically reduced as practitioners have achieved greater familiarity with smaller doses and with signs of clinical effect. Nevertheless, a regular system of monitoring is required to assess respiratory depression. Clinical signs that predict impending respiratory depression are progressive somnolence, small pupils, and smaller tidal volumes. Fentanyl shows less rostral spread when administered spinally or epidurally. It is most conveniently administered via a continuous epidural infusion. For operations below the umbilicus, lumbar or caudal epidural fentanyl infusion may be preferable to lumbar or caudal epidural morphine, because ofless rostral spread and probably a lower incidence of somnolence, nausea, and pruritus. Local anesthetics and opioids are very synergistic in their analgesic effects when administered epidurally. A growing consensus suggests that low-dose infusions of combinations of these medications (usually bupivacaine and fentanyl or bupivacaine and morphine) offer a higher therapeutic ratio than either compound alone. 32, 41, 57 In our hospital, a combined infusion of dilute bupivacaine and fentanyl has become the preferred epidural infusion solution for patients of all ages for major surgery below the umbilicus. With continuous epidural analgesia, urinary retention is very common. Thus, in choosing the technique, the clinician must either restrict it to patients who have bladder catheterization anyway for reasons related to surgery (for example, major urologic surgery and major thoracoabdominal surgery) or they must decide that, in a particular case, the morbidity of bladder catheterization is outweighed by other aspects of the patient's medical condition (for example, major hip or femur osteotomy in a patient with end-stage cystic fibrosiS). The use of innovative techniques such as PCA and prolonged regional blockade (as opposed to single-shot peripheral or central blockade in the operating room) presupposes a well-organized system for ongoing management in the postoperative period, that is, an acute pain service. 9 For hospitals that practice epidural analgesia infrequently, it may be preferable to restrict its use to patients with very clear indications (for example, thoracotomy in a patient with severe lung disease due to cystic fibroSiS)

PEDIATRIC POSTOPERATIVE PAIN MANAGEMENT

935

Appendix. Case Examples 1.

CLINICAL SITUATIONS, 4-YEAR-OLD HEALTHY CHILD UNDERGOING MAJOR HIP OSTEOTOMY.

Considerations A. Very painful surgery B. No particular contraindication to opioids C. Bladder catheter relatively contraindicated .............. D. Too young for PCA Recommendations A. Begin with a parenteral opioid 1) Continuous morphine infusion, or 2) intermittent IV methadone (loading intra-op, then sliding scale) B. Acetaminophen around-the-clock, pr then po when tolerated C. Switch to oral opioid the next day, if oral fluids are tolerated (morphine or metadone while the pain is severe, then codeine) 2.

CLINICAL SITUATION, 14-YEAR-OLD PATIENT WITH IDIOPATHIC SCOLIOSIS (55° CURVE) FOR POSTERIOR FUSION AND INSTRUMENTATION.

Considerations A. Very painful surgery B. Bladder catheter in place C. No particular contraindication to opioids, adequate pulmonary function D. Old enough for PCA E. Usually receives overnight stay in ICU or recovery room Recommendations A. Opioids 1) Single dose intrathecal morphine intra-op followed by PCA, or 2) IV morphine titrated until comfortable in recovery room, then either PCA or continuous IV morphine infusion, or 3) IV methadone loading and sliding scale. 4) Begin oral opioid day 2 post-op if tolerated, either morphine, methadone, or oxycodone B. Acetaminophen C. Begin NSAID day 3 post-op if GI function is good 3.

CLINICAL SITUATION, 5-WEEK-OLD INFANT, FORMER 2B-WEEK PREMATURE, WITH ONGOING APNEIC SPELLS, FOR INGUINAL HERNIA REPAIR.

Considerations A. Increased risk for serious apnea post-op B. Only moderate post-op pain C. Opioids relatively contraindicated D. Bladder catheterization relatively contraindicated Recommendations A. Ilioinguinal/iliohypogastric or caudal block with bupivacaine B. Acetaminophen C. Avoid opioids either intra-op or post-op 4.

CLINICAL SITUATION, B-YEAR-OLD PATIENT WITH ESOPHAGEAL STRICTURE, FOR COLON INTERPOSITION

Considerations A. Very painful surgery B. Major thoracoabdominal dissection; high risk for pulmonary dysfunction post-op; post-op pain inhibits coughing C. Bladder catheter in place D. Usually warrants at least an overnight stay in ICU or recovery room E. No particular contraindication to opioids F. Use of PCA in this age group possible, but controversial G. Any regional technique would require coverage of many dermatomes; operative area not entirely unilaterally innervated Recommendations A. Lumbar epidural morphine administration via a continuous catheter (if expertise aVailable) for 3 to 5 days, then parenteral opioid (it will be several days before gastric route is available) B. Intercostal blocks with bupivacaine by the surgeon under direct vision prior to closing the chest C. If expertise with lumbar epidural not available, begin parenteral opioid, e. g., continuous IV morphine infusiOn, immediately

936

CHARLES B. BERDE

and to observe those patients in an intensive care unit postoperatively. It is my view that with proper development of nursing expertise and protocols, it is practical and safe to care for many of these patients on nursing units outside the intensive care areas. 10 The importance of regularly agreed-upon practices and communication among nurses, anesthesiologists, surgeons, and pediatricians cannot be overemphasized. In recommending a particular technique of analgesia following a particular operation, then, the choice of technique depends in part on local expertise and the availability of services in that hospital. For example, if a patient has to wait for an epidural or interpleural catheter reinjection because the anesthesiologist on call is occupied in the operating room, then the theoretic advantages of the technique are completely negated in practice, and again a pain cycle ensues. In this setting, a continuous intravenous opioid infusion or PCA may be preferable. In the author's institution, reinjections are performed by an anesthesiologist on call for the acute pain service, who has no operating room responsibilities. Even in this setting, use of continuous epidural infusions improves care by preventing the recurrence of pain prior to bolus reinjections. Appendix 1 outlines some representative clinical situations and the author's views regarding preferred analgesic techniques. Prolonged Postoperative Pain In a small percentage of cases, postoperative pain does not follow its usual course of diminishing progressively over the first 3 days to 2 weeks. 4, 89 Neuropathic pain syndromes (causalgia, nerve contusion, stretch, entrapment, painful neuroma, and so forth) should be considered in these cases and may require specific evaluation and treatment.

CONCLUSION Methods are available to relieve postoperative pain in the great majority of children. The major barriers to treatment are lack of information and lack of establishment of pain treatment as a priority. 3, 61 The single greatest problem lies in the provision of inadequate doses of opioids at infrequent intervals via the noxious intramuscular route. Simple provision of nearly constant opioid levels via a painless route (intravenous, oral, and so forth) would dramatically improve the care of children following surgery. The use of acute pain services permits the introduction of a coordinated approach to postoperative pain services that includes techniques such as continuous opioid infusions, PCA, and epidural infusions.

REFERENCES 1. Abajian Je, Mellish RWP, Browne AF, et al: Spinal anesthesia for surgery in the highrisk infant. Anesth Analg 63:359-362, 1984 2. Anand KJS, Hickey PR: Pain and its effects on the human neonate and fetus. N Engl J Med 317:1321-1329, 1987

PEDIATRIC POSTOPERATIVE PAIN MANAGEMENT

937

3. Angell M: The quality of mercy. N Engl J Med 306:98-99, 1982 4. Bach S, Noreng JF, Tjellden NU: Phantom limb pain in amputees during the first 12 months following limb amputation after preoperative lumbar epidural blockade. Pain 33:297-301, 1988 5. Beecher HK: Relationship of significance to wound to the pain experience. JAMA 161:1609-1613, 1956 6. Bennett RL, Batenhorst RL, Foster TS, et aI: Postoperative pulmonary function with patient-controlled analgesia. Anesth Anal 61:171, 1982 7. Bennett R, Batenhorst RL, Bivens BA, et al: Patient-controlled analgesia: A new concept of postoperative pain relief. Ann Surg 195:700--705, 1982 8. Berde CB, Holzman RS, Sethna NF, et aI: A comparison of methadone and md\;phine for post-operative analgesia in children and adolescents. Anesthesiology 69:A768,1988 9. Berde CB, Lacouture PG, Masek BJ, et al: Initial experience with a multidisciplinary pediatric pain treatment service [suppIJ. Pain 4:S99, 1987 10. Berde CB, Sethna NF: Regional anesthetic approaches to postoperative pain in children and adolescents. Intensive Care Med 13:460, 1987 11. Berde CB, Sethna NF, Holzman RS, et al: Pharmacokinetics of methadone in children and adolescents in the perioperative period. Anesthesiology 67:A519, 1987 12. Berry FA: Analgesia in patients with fracture shaft of femur. Anaesthesia 32:576-577, 1977 13. Beyer J, DeGood DE, Ashley LC, Russell GA: Patterns of postoperative analgesic use with adults and children following cardiac surgery. Pain 17:71-81, 1983 14. Blaise G, Roy WL: Postoperative pain relief after hypospadias repair in pediatric patients: Regional analgesia versus systemic analgesis. Anesthesiology 65:84-86, 1986 15. Boas RA, Holford NHG, Villiger JW: Opiate drug choice and drug use. Clin J Pain 1:117125, 1985 16. Bray RJ: Postoperative analgesia provided by morphine infusion in children. Anaesthesia 38:1075-1078, 1983 17. Broadman LM, Hannallah RS, Norden JM, McGill WA: "Kiddie" caudals: Experience with 1154 consecutive cases without complications. Anesth Analg 66:S18, 1987 18. Broadman LM, Higgins TT, Hannallah RS, et aI: Intraoperative subarachnoid morphine for postoperative pain control following Harrington rod instrumentation in children. Can J Anaesth 34:S96, 1987 19. Brown RE, Broadman LM: Patient controlled analgesia (PCA) for postoperative pain control in adolescents. Anesth Analg 66:S22, 1987 20. Brzustowicz RM, Nelson DA, Betts EK, et al: Efficacy of oral premedication for pediatric outpatient surgery. Anesthesiology 60:475-477, 1984 21. Cuschieri RJ, Morran CG, Howie JC, McArdle CS: Postoperative pain and pulmonary complications: Comparison of three analgesic regimens. Br J Surg 72:495-498, 1985 22. Dahlstrom B, Bolme P, Feychting H, et aI: Morphine kinetics in children. Clin Pharmacol Ther 453:365, 1979 23. Dixon S, Snyder J, Holve R, Bromberger P: Behavioral effects of circumcision with and without anesthesia. J Dev Behav Pediatr 5:246-250, 1984 24. Dodd E, Wang JM, Rauck RL: Patient-controlled analgesia for postsurgical pediatric patients ages 6-16 years. Anesthesiology 69:A372, 1988 25. Eckenhoff JE: Relationship of anesthesia to post-operative personality changes in children. Am J Dis Child 86:587-591, 1953 26. Ecoffey C, Attia J, Samii K: Analgesia and side effects following epidural morphine in children. Anesthesiology 63:A470, 1985 27. Ecoffey C, Dubousset AM, Samii K: Lumbar and thoracic epidural anesthesia for urologic and upper abdominal surgery in infants and children. Anesthesiology 65:87-90, 1986 28. Egbert LK, Bettit GE, Welch CE, et aI: Reduction of postoperative pain by encouragement and instruction of patients. N Engl J Med 270:825-827, 1964 29. Eland JM, Anderson JE: The experience of pain in children. In Jacox A (ed): Pain: A Sourcebook for Nurses and Other Professionals. Boston, Little, Brown & Co, 1977 30. Elder PRo Post circumcision pain. A prospective evaluation of subcutaneous ring block of the penis. Regional Anesthesia 9:48-49, 1984 31. Eriksson E: Axillary brachial plexus anaesthesia in children with Citanest. Acta Anaesth Scand 16:291-296, 1965 32. Fischer R, Lubenow TR, Liceaga A, et al: A comparison of continuous epidural infusion

938

33. 34. 35. 36. 37. 38.

39. 40. 41. 42. 43.

44. 45. 46.

47. 48. 49. 50. 51. 52. 53.

54. 55. 56. 57. 58.

CHARLES B. BERDE

of fentanyl-bupivicaine and morphine-bupivicaine in management of postoperative pain. Anesth Analg 66:559-563, 1988 Gardner GG, Olness K: Some guidelines for uses of hypnotherapy in pediatrics. Pediatrics 62:228-233, 1978 Gaudreault P, Guay J, NicolO, Dupuis C: Pharmacokinetics and clinical efficacy of intrarectal solution of acetaminophen. Can J Anaesth 35:149-152, 1988 Glenski JA, Warner MA, Dawson B, Kaufman B: Postoperative use of epidurally administered morphine in children and adolescents. Mayo Clin 59:530-533, 1984 Goettling MG, Thirma MJ: Neurotoxicity of meperidine. Ann Emerg Med 14:1007-1009, 1985 Goulding FJ: Penile block for postoperative pain reliefin penile surgery. J Uroll26:337338, 1981 Gourlay GK, Wilson PR, Glynn CJ: Pharmacodynamics and pharmacokinetics of methadone during the perioperative period. Anesthesiology 57:458-467, 1982 Graves DA, Foster TS, Batenhorst RL, et al: Patient-controlled analgesia. Ann Intern Med 99:~66, 1983 Greeley WJ, deBruijn NP, David DP: Sufentanil pharmacokinetics in pediatric patients. Anesth Analg 66:1067-1072, 1987 Gregg RV, Denson DD, Knarr DC, Steubing RC: Continuous epidural infusions of bupivacaine and morphine versus systemic narcotic analgesics for postoperative pain relief. Anesthesiology 69:A384, 1988 Gregory GA, Steward DJ: Life-threatening perioperative apnea in the ex-"preemie". Anesthesiology 59:495--498, 1983 Grossbard GD, Love BRT: Femoral nerve block: A simple and safe method of instant analgesia for femoral shaft fractures in children. Aust NZ J Surg 49:592-594, 1979 Hannallah RS, Rosales JK: Experience with parents' presence during anesthesia induction in children. Can Anaesth Soc J 30:286-289, 1983 Hertzka RE, Fisher DM, Gauntlett IS, Spellman BS: Are infants sensitive to respiratory depression from fentanyl? Anesthesiology 67:A512, 1987 Holley FD, van-Steenis C: Postoperative analgesia with fentanyl: Pharmacokinetics and pharmacodynamics of constant-rate I. V. and transdermal delivery. Br J Anaesth 60:608613,1988 Jeans ME: The measurement of pain in children. In Melzak R (ed): Pain Measurement and Assessment. New York, Raven Press, 1983 Jensen BH: Cauda block for postoperative pain relief in children after genital operations. A comparison between bupivacaine and morphine. Acta Anaesth Scand 25:373-375, 1981 Johnson KL, Erickson JP, Halley FD, Scott JC: Pharmacokinetics of fentanyl in the pediatric population. Anesthesiology 61:1441, 1984 Jones SEF, MacFarlane DWR, Davis JM, Hall-Davies G: Intrathecal morphine for postoperative pain reliefin children. Br J Anesthesiol 56:137-140, 1984 Kehlet H: Modification of responses to surgery by neural blockade: Clinical implications. In Cousins MJ, Bridenbaugh PD (eds): Neural Blockade in Clinical Anesthesia and Management of Pain. Edition 2. Philadelphia, JB Lippincott, 1988, pp 145-188 Kirya C, Werthmann MW: Neonatal circumcision and penile dorsal nerve block-a painless procedure. Pediatr 92:998-1000, 1978 Koren G, Butt W, Chinyanga H, et al: Postoperative morphine infusion in newborn infants: Assessment of disposition characteristics and safety. J Pediatr 107:963--967, 1985 Krane EJ, Jacobson LE, Lynn AM, et al: Caudal morphine for postoperative analgesia in children: A comparison with caudal bupivacaine and intravenous morphine. Anesth Analg 66:647-653, 1987 Liu MPL, Cote CJ, Goudsouzian NG, et al: Life-threatening apnea in infants recovering from anesthesia. Anesthesiology 59:506-510, 1983 Loeser JD, Black RG, Christman A: Relief of pain by transcutaneous stimulation. J Neurosurg 42:308-314,1975 Lubenow TR, Fischer RL, Besser TP, et al: Comparison of continuous epidural infusions of sufentanil-bupivacaine with morphine-bupivacaine. Anesthesiology 69:A397, 1988 Lunn IN: Postoperative analgesia after circumcision, a randomized comparison between caudal analgesia and intramuscular morphine in boys. Anaesthesia 34:552-554, 1979

PEDIATRIC POSTOPERATIVE PAIN MANAGEMENT

939

59. Lynn AM, Slattery JT: Morphine pharmacokinetics in early infancy. Anesthesiology 66:136-139, 1987 60. Lynn AM, Slattery JT: Pharmacokinetics of morphine sulfate in early infancy. Anesthesiology 63:3A, 1985 61. Marks RM, Sacher EJ, Undertreatment of medical inpatients with narcotic analgesics. Ann Intern Med 78:173-181, 1973 62. Masek BJ, Russo DC, Varni JW: Behavioral approaches to the management of chronic pain in children. Pediatr Clin North Am 31:1113-1129, 1984 63. Mather L, Mackie J: The incidence of postoperative pain in children. Pain 15:271-282, 1983 64. Maunuksela EL, Olkkola KT, Korpela R: Does prophylactic intravenous infusion of indomethacin improve the management of postoperative pain in children? Can J Anaesth 35:123-127, 1988 65. Maxwell LG, Yaster M, Wetzel RC: Penile nerve block reduces the physiologic stress of newborn circumcision [abstract). Anesthesiology 65:A432, 1986 66. May AE, Wandless J, James RH: Analgesia for circumcision in children: A comparison of caudal bupivacaine and intramuscular buprenorphine. Acta Anaesthesiol Scand 26:331, 1982 67. McGrath PA: An assessment of children's pain: A review of behavioral, physiological and direct scaling techniques. Pain 3:147-176, 1987 68. McGrath pJ, Unruh AM: The Measurement and Assessment of Pain. Amsterdam, Elsevier Science Publishers, 1987, pp 73-103 69. McIlvaine WB, Knox RF, Fennessey PV, Goldstein M: Continuous infusion ofbupivacaine via intrapleural catheter for analgesia after thoracotomy in children. Anesthesiology 69:261-264, 1988 70. McIlvaine WB, Knox RF, Jones M, et al: Continuous infusion of bupivacaine via interpleural catheter for analgesia after thoracotomy in children [abstract). ASRA 12:2526, 1987 71. McQuay HJ, Carroll D, Moore RA: Postoperative orthopaedic pain-the effect of opiate premedication and local anaesthetic blocks. Pain 33:291-295, 1988 72. Means LJ, Allen HM, Lookabill SJ, Krishna G: Recovery room initiation of patientcontrolled analgesia in pediatric patients. Anesthesiology 69:A772, 1989 73. Miser AW, Davis DM, Hughes CS, et aI: Continuous subcutaneous infusion of morphine in children with cancer. Am J Dis Child 137:383-385, 1983 74. Miser AW, Miser JS, Clark BS: Continuous intravenous infusion of morphine sulfate for control of severe pain in children with terminal malignancy. J Pediatr 96:930-932, 1980 75. Myers EF, Muravchick S: Anesthesia induction techniques in pediatric patients: A controlled study of behavioral consequences. Anesth Analg 56:538-542, 1977 76. Newman RG: Sounding Board-The need to redefine "addiction." N Engl J Med 308:10961098, 1983 77. O'Hara M, McGrath pJ, Dastoous J, Vair CA: Oral morphine versus injected meperidine (Demerol) for pain relief after orthopedic surgery. J Pediatr Orthop 7:78-82, 1987 78. Payne R: Principles of Analgesic Use in the Treatment of Acute Pain and Chronic Cancer Pain. Report of a Committee to the American Pain Society. Washington, DC, American Pain Society, 1987 79. Reiestad F, Stromskag KE: Interpleural catheter in the management of postoperative pain: A preliminary report. Reg Anesth 11:89-91, 1986 80. Rosen K, Rosen D, Bank E: Caudal morphine for post-op pain control in children undergoing cardiac procedures. Anesthesiology 67:3A, 1987 81. Ross DM, Ross SA: Pain instruction with third-and-fourth-grade children: A pilot study. J Pediatr Psychol 10:55-63, 1985 82. Rumack BH: Aspirin versus acetaminophen: A comparative view. Pediatrics 62:943-946, 1978 83. Schechter NL: Pain and pain control in children. Curr Prob Ped 15:1-67, 1985 84. Schechter NL, Hanson K, Allen D: Are We Undertreating Pain in Children [abstract)? Washington, D.C., Ambulatory Pediatrics Association, 1984 85. Sethna NF, Berde CB: Pediatric regional anesthesia. In Gregory GA (ed): Pediatric Anesthesia. New York, Churchill Livingstone, 1989, in press 86. Singleton MA, Rosen JI, Fisher DM: Plasma concentrations of fentanyl in infants, children and adults. Anaesthesia 34:152-155, 1987

940

CHARLES B. BERDE

87. Stiehm ER: Nonsteroidal anti-inflammatory drugs in pediatric patients. Am J Dis Child 142:1281-1282, 1988 88. Tree-Trakarn T, Pirayavaraporn S: Postoperative pain relief for circumcision in children: Comparison among morphine, nerve block, and topical analgesia, Anesthesiology 62:519-522, 1985 89. Wall PD: The prevention of postoperative pain. Pain 33:289--290, 1988 90. Wall PD, Sweet WHo Temporary abolition of pain in man. Science 155:108--109, 1967 91. Walters J, Christianson L, Nicolson SC, et al: Oral versus intramuscular premedication for pediatric inpatients. Anesthesiology 59:A545, 1983 92. Williamson PS, Williamson ML: Physiologic stress reduction by a local anesthetic during newborn circumcision. Pediatrics 71:36--40, 1983 93. WoolfCJ, Wiesenfield-Hallin Z: The systemic administration oflocal anaesthetics produce a selective depression ofC-afferent fibre evoked activity in the spinal cord. Pain 23:361374, 1985 94. Yaster M: The dose-response of fentanyl in neonatal anesthesia. Anesthesiology 66:433435, 1987 95. Yaster M, Deshpande JK: Management of pediatric pain with opioid analgesics. J Pediatr 113:421--429, 1988 96. Yeager MP, Glass DD, Neff RK, Brinck-Johnsen T: Epidural anesthesia and analgesia in high-risk surgical patients. Anesthesiology 66:729--776, 1987 97. Zeltzer L, LeBaron S: Hypnotic and nonhypnotic techniques for reduction of pain and anxiety during painful procedures in children and adolescents with cancer. J Pediatr 101: 1032--1035, 1982 Department of Anesthesia The Children's Hospital 300 Longwood Avenue Boston, MA 02115