Motoyama & Davis: Smith's Anesthesia for Infants and Children, 7th ed.

PART TWO – General Approach to Pediatric Anesthesia

Chapter 13 – Pain Management in Infants and Children

Steven J. Weisman,Lynn M. Rusy



Undertreatment of Pediatric Pain in children, 436



Neurophysiology of Pain, 438



Neurodevelopment and Nociception, 438



Assessment of Pain, 438



Pharmacologic Approaches to Pain Management, 440 



Nonsteroidal Anti-Inflammatory Drugs,440



Opioids, 441



Other Drugs, 443



Acute Pain Management, 444 



Topical Anesthesia, 444



Patient-Controlled Analgesia, 444



Continuous Intravenous Opioids,445



Epidural Analgesia, 445



Chronic Pain Management, 447 



Organization of the Multidisciplinary Pain Team,448



Headache, 448



Chronic Abdominal Pain, 448



Myofascial Pain/Fibromyalgia, 449



Complex Regional Pain Syndrome, 449



Sickle Cell Anemia, 450



Cancer, 450



Alternative Forms of Pain Management, 451 



Cognitive-Behavioral Interventions, 451



Transcutaneous Electrical Nerve Stimulation,451



Acupuncture, 451



Summary, 451

The International Association for the Study of Pain defines pain as “an unpleasant sensory and emotional experience associated with actual or potential tissue damage, or described in terms of such damage” ( Merskey and Bogduk, 1994 ). In children, even the definition of pain has been debated ( Anand and Craig, 1996 ). Pain is a complex constellation of unpleasant sensory, perceptual, and emotional experiences and certain associated autonomic, psychological, emotional, and behavioral responses. In many newborns or infants, as well as others who have mental retardation, are comatose, are severely demented, or are verbally handicapped, pain cannot be described in such self-report terms. In fact, pain experienced by infants and children often goes unrecognized, even neglected, because of the operational definition of pain that requires self-report ( Walco et al., 1994 ; Anand and Craig, 1996 ). Untreated pain in children, as the result of vaccinations and blood draws, surgery, headaches, or repeated painful procedures, can have long-term effects ( McGrath and Unruh, 1987 ).

Pain management is an essential component of care provided by pediatric anesthesiologists. Most obvious, of course, is the integration of a pain management plan into the overall perioperative plan. In addition, since the 1990s, many pediatric anesthesiologists have become the pain management experts in their institutions. This is particularly true in many of the freestanding children's hospitals that do not have ready access to more mature and developed adult pain management services. This chapter outlines developmental issues in pain management, measurement of pain in children, pharmacologic ways to treat pain (including opioid infusions, patient-controlled analgesia [PCA], epidural anesthesia, single-shot caudal blocks), behavioral pain management, physical modalities for pain management (transcutaneous electrical nerve stimulation [TENS] units), and alternative techniques (acupuncture) now being used in children to manage pain. A glossary of terms used in this chapter is given in Box 13-1.

BOX 13-1 

Abbreviations in Pain Management


Agency for Health Care Policy and Research




Joint Commission for the Accreditation ofHealthcare Organizations




Patient-controlled analgesia


Recurrent abdominal pain


Selective serotonin reuptake inhibitors




Tricyclic antidepressants


Transcutaneous electrical nerve stimulation


For many years, it has been recognized that pediatric patients are more likely to have pain treated less aggressively than are their adult counterparts ( Eland, 1974 ; Asprey, 1994 ; Ferrell et al., 1995 ;Bildner and Krechel, 1996 ; Twycross et al., 1999 ; Sahler et al., 2000 ). Unfortunately, one can argue that this has led to a considerable amount of unnecessary suffering on the part of these patients. In addition, this may have contributed to a collective sense of guilt on the part of the health care provider teams that results in rationalization for policies and procedures that lead to undertreatment ( Craig et al., 1996 ). Children have consistently been offered and/or received fewer, smaller, and less frequent doses of opioid analgesics ( McCaffery and Hart, 1976 ; Perry and Heidrich, 1982 ; Beyer et al., 1983 ;Mather and Mackie, 1983 ; Sriwatanakul et al., 1983 ; Schechter and Allen, 1986 ).

Most health care professionals, even many in surgical specialties, do not receive formal training in pain management ( Taylor and Harris, 1997 ; Sloan et al., 1998 ; Ferrell et al., 2000 ; Fins and Nilson, 2000 ; Sahler et al., 2000 ; Jubelirer et al., 2001 ). In addition, even pediatricians lack relatively easy access to information about pain management. For example, a survey of major textbooks in pediatrics shows the minimal amount of pain management information that is available ( Table 13-1 ). Despite the fact that more than 80% of children who present for nonroutine care have pain as a chief complaint, these 13,811 pages of pediatric text contain only 68 pages that address pain management. Many students complete medical school with only 1 to 2 hours of analgesic pharmacology lectures incorporated into their initial pharmacology course. In addition, although most practitioners involved in the care of children are well aware of the benefits of cognitive-behavioral interventions for pain or procedure management, few ever receive formal training to help incorporate these techniques into daily practice ( Eland, 1974 ; Asprey, 1994 ). Johnston and others (1992) surveyed 150 hospitalized children and found that more than 87% reported having had pain within 24 hours and, of these, 19% reported their usual pain intensity as being in the severe range. Only 38% of the children received analgesic medication during the preceding 24 hours. Broome and others (1996) reported the results of a survey of pain management in pediatric residency training programs. Sixty percent of the respondents were aware of institutional standards of care or protocols for pain management, but only one fourth reported that the standards were followed 80% or more of the time. In another survey of hospitalized children,Cummings and others (1996) reported on patient or parent interviews that were conducted in 200 patients. They reported the intensity and source of the worst, usual, and current pain during the past 24 hours and the help received for pain. Forty-nine percent of the children had clinically significant levels of worst pain. Twenty-one percent had clinically significant levels of usual pain. The causes of pain included disease, surgery, and intravenous catheters. Children received significantly less medication than was prescribed, regardless of the reported pain level. In addition, many children identified “no one” as being helpful in relieving their pain.

TABLE 13-1   -- Survey of major pediatrietextbooks


Year of Publication


Total No. of Pages in Text Management[*]

No. of Chapters on Pain

No. of Pages on Pain Management[*]

Oski's pediatrics: Principles and practice/McMillan, DeAngelis, Feigin, Warshaw/Lippincott Williams and Wilkins






Primary pediatric care/Hoekelman/Mosby






Gellis and Kagans current pediatrie therapy/Burg, Ingelfinger, Polin, Gershon/Saunders






Current pediatrie diagnosis and treatment/Hay, Hayward, Levin, Sondheimer/McGraw-Hill/Appleton & Lange






Rudolph's pediatrics/Rudolph, Rudolph, Hostetter, Lister, Siegel/McGraw-Hill Professional






Saunders manual of pediatriepractice/Finberg, Kleinman/W.B. Saunders






Nelson textbook of pediatrics editionText with continually updated online reference/Behrman/W.B. Saunders













Chapters dedicated to pain management were identified Total number of pages of text present n either these chapters or other sections of the bookwere calculated.


Since 1990, many different national and international standards for pain management have been released. Although there have been individual examples of intensive local efforts to implement some of these guidelines, in general, the guidelines have not been adopted as practice guidelines. McMillan and others (2000) surveyed nurses at two large veterans hospitals and found that even 7 years after the initial Agency for Health Care Policy and Research (AHCPR) guideline was released, nurses continued to have major knowledge deficits about the physiology and pharmacology of pain. The majority of nurses did not agree that patients and their families should have the most control over analgesic scheduling and that a constant level of analgesic should be maintained in the blood. In fact, 82% indicated that around-the-clock analgesics increase the risk for sedation and respiratory depression. Dalton and others (1999) developed a comprehensive program to implement the AHCPR 1992 acute pain management guideline in 6 community hospitals. They were able to demonstrate improved pain assessment and documentation, as well as improved practice in the adopting hospitals.

In 1999, in the United States, the Joint Commission for the Accreditation of Healthcare Organizations (JCAHO) incorporated comprehensive standards of pain management into all of its clinical care manuals. The ripple effects from this are quite evident in the medical, nursing, and administrative communities of all health care organizations. Organizations are beginning to report improvement in assessment and management of pain as well as improvements in satisfaction by patients and their families ( Phillips, 2000 ; Blank et al., 2001 ; Manworren, 2001 ; Ruzicka and Daniels, 2001 ; Starck et al., 2001 ; Goodman, 2003 ; O'Connor, 2003 ).

Fortunately, pediatric anesthesiologists have become proponents for the improvement of pain management in children. Many children's hospitals have developed acute, chronic, or combined programs for the management of pain in children ( Shapiro et al., 1991 ; Miller, 1996 ; Harmer and Davies, 1998 ; Rawal, 1999 ). In this capacity, pediatric anesthesiologists must remain on the forefront of knowledgeable and safe use of a variety of pain interventions for infants and children.

Copyright © 2008 Elsevier Inc. All rights reserved. -

Motoyama & Davis: Smith's Anesthesia for Infants and Children, 7th ed.

Copyright © 2005 Mosby, An Imprint of Elsevier


A variety of chemical, thermal, or mechanical insults can result in the sensation of pain. A mosaic of pain receptors or nociceptors in the body tissues ultimately project to pain centers in the brain. The somatosensory system is subserved by different groups of afferent fibers differentiated by their anatomy, rate of transmission, and sensory modality transmitted. The fibers relay pain information to the dorsal horn of the spinal cord and then on to the brain. These fibers include rapidly conducting, small-diameter C-fibers and thinly myelinated A-δ fibers. The majority of nociceptive input to the central nervous system is carried by C-fibers.

The dorsal horn is organized into fairly discreet lamellae. The primary afferent first-order synapses (nociceptive-specific neurons) are usually located in layers 1, 2, and 5 of the dorsal horn. Signals are then relayed rostrally to the thalamus and the cortex. In addition, afferent impulses are carried to the brainstem, limbic system, and hypothalamus to mediate many of the autonomic and affective component responses to noxious stimuli. Deeper in the dorsal horn are located wide dynamic range neurons (class 2 neurons) that appear to be important in the development of hyperalgesia, or wind-up. These synapses in lamella 5 process signals from hair movement and weak mechanical stimuli. However, they also respond vigorously to a variety of other tissue-damaging stimuli. These neurons may be responsible for firing in pain syndromes that are not associated with obvious tissue damage as well. Reviews of the mechanisms of pain transduction, processing, and modulation have been published by Woolf and colleagues (Costigan and Woolf, 2000, 2002 [92] [91]; Woolf and Max, 2001 ).

Copyright © 2008 Elsevier Inc. All rights reserved. -

Motoyama & Davis: Smith's Anesthesia for Infants and Children, 7th ed.

Copyright © 2005 Mosby, An Imprint of Elsevier


Until recently, physicians also lacked a clear understanding of the normal development of nociception in young or premature infants ( Schechter and Allen, 1986 ; Anand and Hickey, 1987 ; Anand, 1998 ). Their nervous system is immature, and it has been shown that there is incomplete myelination of the nerve tracts bearing afferent impulses. Pain perception does begin before birth, and potent analgesics alter the stress response to surgery, even in premature infants. The landmark article published by Anand and Hickey in 1987 clearly addressed the issue that newborns and infants do in fact experience pain. In addition, the same investigators demonstrated that infants undergoing cardiac procedures do much better clinically if treated appropriately for pain ( Anand and Hickey, 1992 ). Infants received either high-dose opioid (sufentanil) intraoperatively and postoperatively or halothane for surgery and morphine on an as-needed basis in the cardiac intensive care unit. Plasma levels of epinephrine, norepinephrine, glucagon, corticosterone, 11-deoxycorticosterone, and 11-deoxycortisol were significantly elevated in the halothane group up to 24 hours after surgery. They clearly demonstrated that the group that received the sufentanil had greater hemodynamic stability, required less postoperative ventilatory support, and had improved clinical outcome as measured by these markers. The reduced hormonal response and improved clinical outcome following surgery led to the conclusion that neonates do experience pain and that this pain needs to be controlled ( Rogers, 1992 ).

This has also led to speculation that the fetus is capable of experiencing clinically meaningful pain. The anatomic requirements for pain are in place before birth ( Anand and Hickey, 1987 ). Fitzgerald (1994) reviewed the biologic development of the fetus and showed that at 7.5 weeks, there are reflex responses to somatic stimuli. Touching the perioral region results in bending the head away from the stimulus, and repeated stimulation of the limbs at 10 weeks results in hyperexcitability, interpreted as evidence for a functional pain system, even in the very young fetus ( Fitzgerald, 1994 ). Studies observing the muscle response of young infants using electromyography demonstrate a graded response reflective of the stimulus intensity (Andrews and Fitzgerald, 1999, 2000 [18] [19]).

It is important to understand that pain due to surgical procedures not only results in an immediate nociceptive response but also results in changes in the nociceptive activation pathways that lead to hypersensitivity, hyperalgesia, and allodynia. Infants exposed to repeated heel lancing develop hypersensitivity so that mechanical sensory reflex thresholds are reduced on the affected side compared with the nonlanced control side (Fitzgerald et al., 1988, 1989 [134] [132]). Neonatal rats that are studied after repeated needle sticks develop prolonged thermal hyperalgesia ( Anand et al., 1999 ). In other rodent models, newborns demonstrate relatively large nociceptive receptor fields ( Yi and Barr, 1995 ) and immature descending inhibitory systems ( Fitzgerald and Koltzenburg, 1986 ). Actual neural remodeling in the spinal cord has been demonstrated by Ruda and others (2000) in a rat model of chronic inflammation. There was increased sprouting of primary sensory fibers as well as caudal extension in the spinal cord. In addition, there was hyperexcitability in dorsal horn neurons connecting to these fibers, plus abnormal and increased pain behaviors seen later in the adult animals.

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Motoyama & Davis: Smith's Anesthesia for Infants and Children, 7th ed.

Copyright © 2005 Mosby, An Imprint of Elsevier


Children have a more intense physical and emotional reaction to painful procedures than do adults. In the 1800s, Darwin wrote about matching facial expressions to emotions, with pain being one of those he recognized ( Grunau and Craig, 1987 ). In 1986, Johnston and Strada (1986) found that facial expressions are useful markers for pain in infants up to 6 months of age. They found facial expressions to be less well developed in premature babies and a high-pitched cry to be a better marker of pain. Grunau and others (1990) developed the Neonatal Facial Coding System to quantify facial actions in newborns exposed to brief painful stimuli. Various investigators have developed composite observational pain measurement tools to assist in the assessment of pain in the preverbal or nonverbal pediatric populations. Because of neurodevelopmental differences, tools have been refined to accommodate measurement in the premature infant; examples of these tools are given in Tables 13–2 through 13-5 [2] [3] [4] [5].

TABLE 13-2   -- Behavioral and composite pain assessment scales


Target Age




Premature Infant Pain Profile (PIPP)

Preterm and full-term neonates

Gestational age, behavioral state, heart rate, oxygen saturation, brow bulge, eye squeeze, nasolabial furrow

Developed with procedural pain model (heel lance); 0-to-21 scoring

Stevens et al., 1996 ;Ballantyne et al., 1999

Neonatal Infant Pain Scale (NIPS)

Preterm and full-term infants

Facial expression, cry, breathing pattern, arms, legs, state of arousal

Developed with procedural pain model (heel lance); also validated for preterm infants; 0-to-7 scoring

Lawrence et al., 1993; Johnston et al., 1999

CRIES (crying requires O2 saturation,increased vital signs, expression, andsleeplessness)

Full-term neonates

Crying, O2 saturation, heart rate, blood pressure, expression, sleeplessness

Developed with postoperative pain model; 0-to-10 scoring
Krechel and Bildner, 1995


FLACC (face, legs, activity, crying,consolability)

2 mo to 7 yr

Facial expression, crying, legs, activity state, consolability

Developed with postoperative pain model; 0-to-10 scoring

Merkel et al., 1997

Children's Hospital of Eastern Ontario Pain Scale (CHEOPS)

1 to 7 yr

Cry, facial expression, verbalization, torso position, touch (affected area), legs

Developed with postoperative pain model but tested in procedural pain as well; 4-to-13 scoring

McGrath et al., 1985


All ages

Alertness, calmness/agitation, respiratory response, physical movements, heart rate, blood pressure, muscle tone, facial tension

Developed for use in critical care setting (intubated patient); 0-to-40 scoring

Ambuel et al., 1992



TABLE 13-3   -- Children's Hospital of Eastern Ontario Pain Scale (CHEOPS)






No cry


Child is not crying.




Child is moaning or quietly vocalizing, silent cry.




Child is crying but the cry is gentle or whimpering.




Child is in a full-lunged cry; sobbing: may be scored with complaint or without complaint.




Neutral facial expression




Score only if definite negative facial expression.




Score only if definite negative facial expression.

Child Verbal



Child is not talking.


Other complaints


Child complains but not about pain, e.g., “I want to see my mommy,” or “I am thirsty.”


Pain complaints


Child complains about pain.


Both complaints


Child complains about pain and about other things, e.g., “It hurts; I want my mommy.”




Child makes any positive statement or talks about other things without complaint.




Body (not limbs) is at rest; torso is inactive.




Body is in motion in a shifting or serpentine fashion.




Body is arched or rigid.




Body is shuddering or shaking involuntarily.




Child is vertical or in upright position.




Body is restrained.


Not touching


Child is not touching or grabbing at wound.




Child is reaching for but not touching wound.




Child is gently touching wound or wound area.




Child is grabbing vigorously at wound.




Child's arms are restrained.




Legs may be in any position but are relaxed; includes gentle swimming or serpentine-like movements.




Definitive uneasy or restless movements in the legs and/or striking out with foot or feet.


Drawn up/tensed


Legs tensed and/or pulled up tightly to body and kept there.




Standing, crouching, or kneeling




Child's legs are being held down.

From McGrath P, Johnson G, et al.: CHEOPS: A behavioral scale for rating postoperative pain in children. In Fields H, editor: Advances in pain research and therapy. New York, 1985, Raven Press, pp 395–402.




TABLE 13-4   -- FLACC (Face, Legs, Activity, Crying, Consolability) Scale

Rights were not granted to include this content in electronic media. Please refer to the printed book.

From Merkel SI, Voepel-Lewis T, et al.: The FLACC: A behavioral scale for scoring postoperative pain in young children. Pediatr Nurs 23:293–297, 1997.




TABLE 13-5   -- Self-report measures pain assessment scales







>3 yr

Cartoon drawings of faces from smiling to crying with tears

Some cultural variability; 0-to-5 or 0-to-10 scoring

Luttmer and LePage, 1988 ; Wong and Baker, 1988


>3 yr

Line drawings of faces from neutral to crying

Validated for 6-8 yr; 0-to-6 (original) scoring; 0-to-5 or -10 (modified) scoring

Bieri et al., 1990 ; Hicks et al., 2001


>3 yr

Photographs of child from neutral to crying

Available in versions for whites, Hispanics, and blacks; 0-to-100 scoring

Beyer et al., 1992



Wong and Baker (1988) described the original, and possibly most popularized, FACES pain scale for children aged 3 years or older ( Fig. 13-1 ). Bieri and others (1990) investigated the use of facial expressions as a way of rating subtle behaviors. They adapted children's drawings to derive a cartoon scale with more anthropomorphically realistic faces ( Fig. 13-2 ). This scale was revised and validated to correspond to a 0- to 10-point verbal analog scale ( Hicks et al., 2001 ).


FIGURE 13-1  Wong-Baker FACES scale. Scored from 0 to 5; it can also be scored from 0 to 10. Wong and Baker (1988) described the original, and possibly most popularized, FACES pain scale for children aged 3 years or older.  (From Wong DL, Hockenberry–Eaton M, Wilson DJ, et al.: Wong's essentials of pediatric nursing, 8th ed. St. Louis, Mosby, 2001, p 1301.)



FIGURE 13-2  Bieri faces scales. (Top) Original panel. (Bottom) Revised scale corresponding to a 0-to-10 metric. Bieri and others (1990) investigated the use of facial expressions as a way of rating subtle behaviors. They adapted children's drawings to derive a cartoon scale with more anthropomorphically realistic faces. This scale was recently revised and validated to correspond to a 0- to 10-point verbal analog scale.  (From Hicks CL, Baeyer CL, Spaffard PA, et al.: The faces pain scale-revised: Toward a common metric in pediatric pain measurement. Pain 93:173–183, 2001. Copyright © 2001, with permission from the International Association for the Study of Pain.)




Numeric self-report measures are widely accepted for use in children older than 6 to 8 years ( Maunuksela et al., 1987 ; Vetter and Heiner, 1996 ). Although the visual analog scale (10-cm line that is anchored as “no pain” to “worst possible pain” at each end) is often considered the gold standard of pain assessment, in children the verbal analog scale (pain rated from 0 [no pain] to 10 [most pain possible]) may be more reliable ( Briggs and Closs, 1999 ).

Pain assessment in the cognitively impaired child has been a challenge and a barrier to effective pain treatment. As many as 10% of children who are cared for in major pediatric centers have mental retardation, autism, metabolic disorders, neurotrauma, or significant other communication disorders. Breau and others (1999, 2002 [59] [60]) identified common pain problems likely to occur in these children, such as gastroesophageal reflux, muscle spasm, and constipation. In addition, the same group of investigators developed a tool to measure pain in these at-risk children, the Non-Communicating Pain Behavior Check List ( Breau et al., 2002 ).

Individual institutions have developed their own algorithm for a series of pain assessment tools to span the developmental continuum. It is imperative for caretakers to incorporate the various ages or developmentally appropriate tools into their language of pain assessment and management.

Copyright © 2008 Elsevier Inc. All rights reserved. -

Motoyama & Davis: Smith's Anesthesia for Infants and Children, 7th ed.

Copyright © 2005 Mosby, An Imprint of Elsevier


The management of pediatric pain can be accomplished using a multimodal approach in which pharmacologic techniques and nonpharmacologic approaches complement one another. The nonpharmacologic approaches include relaxation training, cognitive-behavioral techniques, biofeedback, physical therapy, occupational therapy, TENS, acupuncture, and progressive muscle relaxation training. We first discuss pharmacologic approaches and, later in the chapter, discuss in greater detail nonpharmacologic ways to manage pain. Unfortunately, nonpharmacologic methods for pain management continue to be underused in children. An in-depth discussion of this topic is, obviously, beyond the scope of this chapter; the reader is referred to an excellent monograph by Lynnda Dahlquist (1999) .


Acetaminophen (paracetamol) is an antipyretic and weak analgesic that blocks prostaglandin synthesis centrally, reduces substance P–induced hyperalgesia, and modulates spinal cord hyperalgesic nitric oxide production ( Bjorkman et al., 1994 ; Bjorkman, 1995 ). It is a weak analgesic indicated for mild pain or as an adjunct for the treatment of moderate or severe pain. Although it produces dose-dependent responses, it is limited by a ceiling effect, above which dose increases do not produce further analgesia ( Skoglund et al., 1991 ; Hahn et al., 2003 ). Acetaminophen is safe to use in neonates, especially because it is primarily metabolized in the liver. Because neonates have immature hepatic function, they are less likely to produce toxic metabolites ( Lesko and Mitchell, 1999 ; van Lingen et al., 1999a, 1999b [360] [361]; Anderson et al., 2002 ). Oral doses of 10 to 15 mg/kg, although antipyretic, are not analgesic until doses of 20 to 35 mg/kg are used ( Anderson and Holford, 1997 ; Anderson et al., 1999). In fact, there is evidence that rectal doses of 40 to 45 mg/kg are needed to achieve effective plasma concentrations ( Korpela et al., 1999 ).

Nonsteroidal anti-inflammatory drugs (NSAIDs) inhibit peripheral cyclooxygenase (COX) and decrease prostaglandin production and are more potent analgesics than acetaminophen ( Malmberg and Yaksh, 1992 ; Yaksh and Malmberg, 1993 ; Yaksh et al., 1998 ). NSAID pharmacology has advanced so that agents have been developed that target the different isozymes of COX. COX-1 is constitutive, whereas COX-2 is induced after trauma and inflammation ( Mitchell et al., 1993 ; Everts et al., 2000 ). Commonly used NSAIDs actively inhibit both COX enzymes ( Table 13-6 ). A newer series of agents have become available that target primarily the COX-2 isozyme. None of these agents have received approval for use in children. However, several reports of the successful perioperative use of celecoxib (Celebrex) and rofecoxib (Vioxx) have been published ( Cummins et al., 2000 ; Pickering et al., 2002 ; Stempak et al., 2002 ; Joshi et al., 2003 ; Kerr et al., 2003 ). These are helpful in mild postoperative pain problems, such as ear tube insertions, inguinal hernia repairs, and other minor surgical procedures.

TABLE 13-6   -- Nonsteroidal anti-inflammatory drugs (NSAIDs)


Age Group

Dose (mg/kg)



Preterm Term

Load: 20; 15(PO), 20 (PR)



>3 mo

Load: 20 to 30; 20 (PO)




Load: 20 (PO); 15 (PO)




40 (PR), 20 (PR)



>1 yr

1 (PO)



>6 mo

10 to 15 (PO)



>6 mo

0.25 to 0.5 (IM, IV)



>6 mo

5 to 10 (PO)



>1 yr

1.5 to 3 (PO)


Note: In the perioperative setting, or in other medical settings where hypovolemia may occur, extreme caution is advised when using NSAIDs (except acetaminophen).




These publications target the opioid-sparing effect of the COX-2 inhibitors in children, as has been clearly documented with several older-generation NSAIDs. Diclofenac and ketorolac have been most extensively studied in this setting ( Nordbladh et al., 1991 ; Maunuksela et al., 1992 ; Watcha et al., 1992 ; Sutters et al., 1995 ; Nishina et al., 2000 ; Park et al., 2000 ; Oztekin et al., 2002 ). Ketorolac remains the only parenteral NSAID used in the perioperative setting. Several injectable COX-2 inhibitors are in development. Because all cells, except red cells, produce prostanoids via the COX pathway, the COX agents have significant toxic effects. Use is limited by gastropathy, inhibition of platelet function, and marked reduction in renal blood flow. The COX-2 inhibitors have marked less gastrointestinal toxicity, as well as no hemostatic effects, but they are still able to induce significant renal toxicity. No data are available on potential cardiovascular toxicity of COX-2 inhibitors in children.


A review of opioid pharmacology can be found in Chapter 6 , Basic Pharmacokinetic Concepts. Opioids are one of the foundations of analgesia in a balanced anesthetic, as well as the basis of analgesia for patients with moderate to severe pain. Opioids are used as part of a “balanced” or multimodal analgesic plan ( Table 13-7 ). Such a plan will incorporate an NSAID, if possible, and/or use of local anesthetics. In addition, careful attention must be paid to the specific neurodevelopmental pharmacology of these drugs, because it affects the distribution and clearance of all the opioid analgesics.

TABLE 13-7   -- Opioid analgesics (μ-agonists)


Equipotent IV Dose (mg/kg)

IV:PO Equivalence

IV Dose (mg/kg)

PO Dose (mg/kg)

Interval (Minimum)








Usually prescribed with acetaminophen; limited analgesia in patients deficient in P450 2D6 isozyme




0.001 to 0.002

Transmucosal: 200-mcg unit smallest available; titrate to effective dose

q1h (IV)

Chest wall rigidity associated with doses >0.005 mg/kg; also available as transdermal system (12.5 to 100 mcg/hr delivery) for chronic pain neuraxial




0.015 to 0.02



May cause less itching and nausea; no active metabolites; good in renal failure; neuraxial







Avoid monoamine oxidase inhibitors; normeperidine (metabolite) causes seizures; only short-term use




0.1 to 0.2 (load)

0.1 to 0.2


Very long-acting







Histamine release; several slow-release oral forms available (MS Contin; Kadian; Avinza, Oramorph SR); neuraxial





0.1 to 0.2


Little nausea or itch; slow-release oral form available (OxyContin); available in combination with acetaminophen or ibuprofen



Morphine and Fentanyl

Premature and term newborns show reduced clearance of morphine and prolonged elimination half-life ( Lynn and Slattery, 1987 ). In opioid naïve young infants, doses that are one fourth to one half of those normally recommended should be used. By 3 to 6 months of age, morphine pharmacokinetics resembles that in older children and adults ( McRorie et al., 1992 ; Lynn et al., 1998 ). Fentanyl has a prolonged elimination half-life and diminished clearance in premature infants and newborns ( Singleton et al., 1987 ). The same authors report that in infants older than 3 months, clearance is actually double that in older children and adults. Because fentanyl clearance is dependent on hepatic blood flow, it must be used with caution in infants who have increased intra-abdominal pressure, particularly during and after surgery ( Yaster, 1987 ; Yaster et al., 1988 ). Small infants, younger than 6 months, who are receiving opioid analgesics must be carefully monitored with pulse oximetry in a setting that provides adequate supervision, if respiratory compromise were to occur.

In many clinical settings, use of continuous opioid infusions may be preferable to the use of intermittent dosing. In general, continuous therapy is used in children who are too young to take advantage of PCA systems. In neonates, because of lowered morphine clearance, continuous infusion should be initiated cautiously, even at dosages as low as 5 mcg/kg per hour ( Hartley et al., 1993 ). Infants between 1 and 3 months of age have been successfully managed with morphine infusions of 10 to 30 mcg/kg per hour ( Bray, 1983 ; Bray et al., 1986, 1996 [55] [56]). Lynn and others (1984) have shown that after a loading dose of 25 to 75 mcg/kg, infusions of 15 to 25 mcg/kg per hour provide adequate postoperative analgesia.

Alternatively, continuous fentanyl infusions are widely used in both pediatric and newborn intensive care units. Loading doses are usually in the 1 to 4 mcg/kg range followed by infusions of 2 to 4 mcg/kg per hour. Fentanyl affords some degree of cardiovascular stability compared with morphine in the very critically ill infant ( Collins et al., 1985 ; Yaster et al., 1987, 1994 [387] [388]).

Success in the use of continuous opioid therapy is often dependent on successful management of side effects or effective dose adjustment in children who continue to have pain. Nausea, vomiting, pruritus, urinary retention, dysphoria, constipation, and somnolence must all be treated promptly ( Table 13-8 ). Inadequate analgesia will be difficult to treat if adjustments are only made to the rate of infusion. If the overall assessment is that the child is having significant pain at the current infusion rate, a bolus dose of approximately 50% of the standard dose for age should be administered and followed by a rate increase of 10% to 20%.

TABLE 13-8   -- Medications commonly used to treat opioid side effects

Side Effect



Diphenhydramine (0.5 mg/kg per dose q6h PRN)




 Naloxone gtt (0.5 to 2 mcg/kg per hour)




 Nalmefene (0.25 to 0.5 mcg/kg per dose scheduled q8h)


Ondansetron (0.15 mg/kg per dose q6h PRN to a maximum of 4 mg/dose)




 Narcan gtt (0.5 to 2 mcg/kg per hour)




 Nalmefene (0.25 to 0.5 mcg/kg per dose scheduled q8h)


Methylphenidate (0.1 mg/kg per dose); consider slow-release preparations

Urinary retention

Naloxone gtt (0.5 to 2 mcg/kg per hour)




 Nalmefene (0.25 to 0.5 mcg/kg per dose scheduled q8h) May require placement of continuous indwelling catheter

Note: Often symptoms can be managed with a reduction in opioid dosing by 20% to 25%. However, this may reduce analgesia and adjunctive therapy should be considered.





Hydromorphone is a phenanthrene derivative of morphine. It is approximately five times more potent than morphine, is nearly as water soluble, and has a similar elimination half-life. Hydromorphone is metabolized to hydromorphone-3-glucuronide, dihydromorphone, and dihydroisomorphine. Its pharmacokinetic profile appears to be similar in children and adults ( Babul et al., 1995 ). There is still some controversy over the clinically relevant side effect profile of hydromorphone. Several authors contend that hydromorphone results in less pruritus and less respiratory depression compared with morphine (Chaplan et al., 1992 ; Goodarzi, 1999 ). Both of these studies examined epidural administration and use equianalgesic conversions well above the 5:1 ratio commonly accepted in children ( Collins et al., 1996 ). Other investigators have found very similar side effects with hydromorphone compared with morphine (Collins, 1996; Halpern et al., 1996 ; Rapp et al., 1996 ; Miller et al., 1999 ). Nonetheless, hydromorphone is an excellent alternative to morphine when one desires opioid rotation in the very tolerant patient, when there are unacceptable morphine side effects, and in patients with significant renal impairment. Although hydromorphone metabolites can accumulate in patients with renal impairment, they do not appear to be associated with the respiratory depressive effects seen with morphine metabolites in these patients ( Babul et al., 1995 ). Hydromorphone does not appear to have significantly active water-soluble metabolites ( Bruera et al., 1996 ; Collins et al., 1996 ).


Methadone is also a μ-agonist, but it has an extremely long elimination half-life of 19 hours in children ( Berde et al., 1991 ). It behaves similarly to a slow-release preparation because of this property. It can be administered intravenously or orally. Berde and colleagues ( Berde et al., 1989 ; Shannon and Berde, 1989) described a convenient and effective technique for the management of postoperative pain using methadone. Patients receive a load of 0.1 to 0.2 mg/kg, usually during the surgery. Postoperative pain management is accomplished by the as-needed administration of doses of 0.03 to 0.08 mg/kg every 4 to 12 hours.

Another important role for methadone is in weaning opioid-tolerant patients ( Tobias et al., 1990 ; Anand and Arnold, 1994 ). Different techniques have been proposed for conversion of morphine to oral methadone equivalents. Siddappa and others (2003) recommend administering methadone as 2.5 times the total daily fentanyl dose each day. Berens and Meyer ( Meyer and Berens, 2001 ; Berens and Meyer, 2002 ) calculate the 24-hour morphine requirement and then administer one sixth of that amount as methadone every 12 hours. In addition, Berens and Meyer suggest, in preliminary data, that opioid-tolerant patients can be successfully weaned over as brief a period as 5 days.


Codeine is a commonly prescribed oral opioid analgesic that is often used for mild to moderate pain. Oral codeine has reasonable oral bioavailability and undergoes hepatic metabolism via O-demethylation to morphine. Interestingly, this conversion relies on the cytochrome P-450 2D6 isozyme, which is absent or diminished in 5% to 10% of certain ethnic populations (Leeder, 2001, 2003 [219] [218]). These individuals have a markedly diminished or absent analgesic response to codeine. This, plus the well-known profile of codeine that includes nausea, vomiting, and constipation, has led many clinicians to switch to either hydrocodone or oxycodone as first-line oral opioid analgesics. Codeine and hydrocodone offer some additional ease in prescribing in that both agents are listed as schedule III opioids, whereas all of the other available agents are listed as schedule II by the Drug Enforcement Agency of the United States. All of these oral opioid analgesics are often used in fixed combination with acetaminophen or ibuprofen. Particularly with the former, attention must be paid to the total daily acetaminophen dose to avoid hepatotoxic levels.


Tramadol is a synthetic analog of codeine that was first introduced in Europe in the late 1970s ( Cossmann et al., 1997 ). It did not receive approval in the United States until 1995, even though it had been extensively used and studied elsewhere. It appears to be a unique analgesic that works via both μ-receptor–mediated activity and inhibition of serotonin and norepinephrine reuptake ( Lee et al., 1993 ;Dayer et al., 1994 ; Goeringer et al., 1997 ). It has excellent oral bioavailability (75%); however, it is metabolized by the cytochrome P-450 hepatic pathways, resulting in potentially significant drug interactions, such as with the tricyclic antidepressants (TCAs). Tramadol has been associated with seizures, especially in patients already on drugs that inhibit hepatic metabolism ( Tobias, 1997 ; Jick et al., 1998 ; Gardner et al., 2000 ; Gasse et al., 2000 ). Tramadol (100 mg) compares favorably, in adults, to hydrocodone/acetaminophen (5 mg/325 mg) ( Turturro et al., 1998 ). Investigators have evaluated the use of tramadol as an adjunct to caudal analgesia ( Baraka et al., 1993 ; Delilkan and Vijayan, 1993 ; Motsch et al., 1997 ; Prosser et al., 1997 ; Russell, 1998 ; Batra et al., 1999 ; Gunduz et al., 2001 ;Ozcengiz et al., 2001 ; Senel et al., 2001 ). Finkel and others (2002) and Rose and others (2003) reported on the use of tramadol (1 to 2 mg/kg per dose every 6 hours) for acute and subacute postoperative pain management.


Oxycodone is a semisynthetic phenanthrene-derivative opioid that is being used more frequently because of the issues touched on earlier regarding codeine. Oxycodone is extensively metabolized to noroxycodone (major) and oxymorphone (minor) and their glucuronide conjugates in the liver ( Weinstein and Gaylord, 1979 ; Ishida et al., 1982 ). Although oxymorphone metabolism is mediated by cytochrome P-450 2D6, blockade of this pathway by concomitant medications or genetic variation has not yet been shown to be of clinical significance with controlled-release oxycodone. Oxycodone has excellent oral bioavailability (≈ 60%). It is available as liquid, tablets, and then in various fixed combinations with acetaminophen, ibuprofen, or aspirin. It is also available in a slow-release form, OxyContin. Although its use in children is off-label, it would appear that it is being used in many situations. Czarnecki and others (2004) , for example, describe its use as an oral analgesic for the management of postoperative pain after spinal fusion. Interestingly, these authors report an OxyContin/intravenous morphine conversion ratio of 1:1. The manufacturer suggests that this ratio be 3:1, from adult studies.


Clonidine is an α2-agonist that has been available for some time for the treatment of hypertension, attention deficit disorder, migraine prophylaxis ( Sillanpaa, 1977 ; Sills et al., 1982 ), and Tourette's syndrome. It has undergone investigation as an analgesic, particularly for neuraxial use ( Eisenach et al., 1996 ). This agent shows promise as part of an analgesic regimen for postoperative and cancer pain. It is associated with hypotension, bradycardia, and somnolence, but it avoids respiratory depression, pruritus, and urinary retention, commonly associated with opioids. It has been given orally, before surgery, and been shown to reduce postoperative analgesic requirements (Mikawa et al., 1995, 1996 [264] [265]; Broadman et al., 1997 ; Goyagi et al., 1999 ). Clonidine is now commonly added to local anesthetics for epidural or caudal block ( Jamali et al., 1994 ; Ivani et al., 1996 , 2000; Luz et al., 1999 ). Epidural doses of 1 to 2 mcg/kg appear safe and not only prolong the duration of analgesia from epidural blockade but can also significantly reduce the need to use opioids. Caution must be taken when using clonidine in neonates or young infants who may be more susceptible to the development of apnea ( Bouchut et al., 2001 ). Clonidine can also be used as a preoperative sedative that also reduces postoperative analgesic requirements ( Mikawa et al., 1996 ; Broadman et al., 1997 ; Reimer et al., 1998; Goyagi et al., 1999 ; Nishina et al., 2000 ; Fazi et al., 2001 ). Doses of 3 to 5 mcg/kg (PO) appear effective. Some clinicians also apply transdermal clonidine for continued analgesia in the postoperative period (0.1 mg/24 hr for patients <40 kg and 0.2 mg/day if >40 kg).

Ketamine is a phencyclidine derivative agent with amnestic, sedative, and analgesic properties. It has been used as a general anesthetic as well as an adjunct for postoperative analgesia ( Cook et al., 1995 ;De Negri et al., 2000 ; Dix et al., 2003 ), chronic pain management ( Stubhaug and Breivik, 1997 ; Fine, 1999 ), and procedural sedation ( Green et al., 1990 ; Tobias et al., 1992 ; Parker et al., 1997 ;Lawrence and Wright, 1998 ; Kennedy and Luhmann, 2001 ). Interestingly, ketamine has been shown to have significant N-methyl-D-aspartate (NMDA) receptor antagonism activity ( Stubhaug and Breivik, 1997 ; Stubhaug et al., 1997 ). Activation of this pathway is thought to play an important role in the development of hyperalgesia and spinal cord windup. In addition, ketamine exerts local anesthetic properties when administered intrathecally. Although it is not yet available in the United States in a suitable neuraxial preparation, its use as an additive to caudal and epidural analgesia has been reported from Europe ( De Negri et al., 2000 ; Koinig et al., 2000 ; Zenz and Zenner, 2000 ).

Tricyclic antidepressants have consistently provided analgesia in a variety of chronic pain conditions including neuropathic pain ( McQuay et al., 1996 ; Sindrup and Jensen, 1999 ; Orza et al., 2000 ), migraine ( Saeed et al., 1992 ; Silberstein et al., 2003 ), and abdominal pain ( Rajagopalan et al., 1998 ; Hyams, 1999 ; Hyams et al., 2002 ). It is thought that these agents are analgesic by inhibiting serotonin and norepinephrine uptake, resulting in facilitating inhibitory neurotransmitter activity at the level of the spinal cord. Because of anticholinergic side effects, most TCAs must be slowly titrated to an effective dose. It is prudent to initiate therapy with either amitriptyline or nortriptyline at 0.2 mg/kg and over 1 to 2 weeks target trial doses of 0.5 to 1.0 mg/kg per day. If sleep disturbance is a part of the pain syndrome, amitriptyline, given 1 to 2 hours before bed, can help facilitate better sleep. Alternatively, nortriptyline can be used at similar doses, because amitriptyline is metabolized to nortriptyline in vivo. Because these drugs can prolong the QTc interval with resultant tachyarrhythmias in patients with predisposing prolonged QTc syndrome, baseline electrocardiography is indicated. In addition, if selective serotonin reuptake inhibitors (SSRIs) are also being used, periodic measurement of TCA levels is also warranted ( Table 13-9 ).

TABLE 13-9   -- Tricyclic antidepressants and anticonvulsants for pain management



Dose Interval



Initial: 0.2 mg/kg per day
Target: 0.5 to 1.0 mg/kg per day

Once each night; 1 to 2 hr before bed.

Sedating; constipating; dry mouth; monitor electrocardiogram; may need to monitor plasma levels


See Amitriptyline

See Amitriptyline

Less sedating and fewer anticholinergic effects


Initial: 5 to 10 mg/kg per day
Target: 15 to 30 mg/kg per day

Divide into 2 or 3 doses.

Blood dyscrasias; must follow plasma levels


Initial: 5 mg/kg per day
Target: 15 to 30 mg/kg per day

Divide into three doses.

Initial sedation; may affect memory

Sodium valproate

Initial: 10 mg/kg per day

Divide into three doses.

Blood dyscrasias; hepatotoxicity; monitor plasma levels, complete blood cell count, liver function tests



Anticonvulsant treatment for chronic pain management has become the mainstay of neuropathic pain disorders ( McQuay, 1988 ; Galer, 1995 ; Backonja, 2000 ; Wallace, 2001 ). In addition, there is considerable support for their use in migraine prophylaxis ( Rapoff et al., 1988 ; Baumel, 1994 ; Grazzi et al., 1998 ; Silberstein et al., 2000 ). Phenytoin, carbamazepine, sodium valproate, and gabapentin are the most commonly used agents. Carbamazepine was the most widely studied and best supported antiepileptic agent for use in neuropathic pain ( Backonja, 2000 ; Wiffen et al., 2000 ; Harke et al., 2001). Gabapentin, which has a much more acceptable side effect profile, has been gathering more attention ( Wetzel and Connelly, 1997 ; Attal et al., 1998 ; Backonja et al., 1998 ; Fudin and Audette, 2000 ;Nicholson, 2000 ; Rusy et al., 2001 ). Unfortunately, virtually all of these studies have been completed in adults and are yet to be replicated in children (see Table 13-9 ).

Copyright © 2008 Elsevier Inc. All rights reserved. -

Motoyama & Davis: Smith's Anesthesia for Infants and Children, 7th ed.

Copyright © 2005 Mosby, An Imprint of Elsevier


Postoperative pain management should begin with preoperative teaching and preparation. Because as many as 70% of pediatric procedures are completed as same-day surgery, a true preoperative visit is often not possible. Nonetheless, a thorough discussion of how pain is going to be managed postoperatively is crucial to both the patient and parent and should take place before surgery. Recovery room nurses can then further instruct the patient and family to reinforce the preoperative teaching. Nonpharmacologic techniques discussed later commonly reduce anxiety and pain and may even reduce the need for opioids or other analgesics. Pharmacologic techniques include nonopioid medications (acetaminophen, NSAIDs, clonidine, and tramadol), opioids, and local anesthetics. A potentially beneficial principle to adhere to for acute postoperative pain management is that local anesthetics should be part of the initial pain management plan. This can be accomplished by using a peripheral regional anesthetic technique, a central neuraxial block, or local infiltration of the surgical site either before or after the procedure.


Painless topical anesthesia has become possible since the introduction of EMLA (eutectic mixture of local anesthetics, 2.5% lidocaine, and 2.5% prilocaine) cream in the 1980s. Application to skin for 60 minutes with an occlusive dressing leads to effective cutaneous anesthesia ( Ehrenstrom-Reiz and Reiz, 1982 ; Hallen and Uppfeldt, 1982 ; Maunuksela and Korpela, 1986 ). EMLA has been studied for use in multiple situations that require trauma to the skin, including venipuncture, intravenous catheter placement, circumcision, port access, shunt access, lumbar puncture, bone marrow aspiration, laceration repair, and even myringotomy ( Cooper et al., 1987 ; Soliman et al., 1988 ; Halperin et al., 1989 ; Miser et al., 1994 ; Calamandrei et al., 1996 ; Taddio et al., 1997 ; Zempsky and Karasic, 1997 ). Other topical creams have subsequently been approved for use that include a 4% liposomal lidocaine mixture or 4% tetracaine gel (Ametop Gel). Both are reported to have quicker onset than EMLA and to cause less local vasoconstriction, which sometimes can obscure veins with EMLA ( Doyle et al., 1993 ; Choy et al., 1999 ; Friedman et al., 1999 ; Chen and Cunningham, 2001 ; Eichenfield et al., 2002 ).

Cutaneous anesthesia can also be achieved using careful intradermal infiltration with local anesthetics. Obviously, most pediatric patients prefer not to undergo a needle puncture procedure. However, if one incorporates the use of buffered lidocaine with a 30-gauge needle, this procedure can be done virtually without discomfort ( McKay et al., 1987 ; Christoph et al., 1988 ; Bartfield et al., 1990 ). Good cutaneous anesthesia can also be achieved in open skin wounds (lacerations) using a fixed combination of either tetracaine/Adrenalin (epinephrine)/cocaine (TAC) or lidocaine/epinephrine/tetracaine (LET) ( Blackburn et al., 1995 ; Ernst et al., 1995 , 1997; Schilling et al., 1995 ; Liebelt, 1997 ; Adler et al., 1998 ; Resch et al., 1998 ; Singer and Stark, 2000 ). TAC, however, has been associated with seizures, especially in young children who have lacerations in more vascular areas, such as the face or scalp ( Fitzmaurice et al., 1990 ).

Several other relatively noninvasive systems have been developed to effect the delivery of lidocaine into the dermis without using a needle-based technique. Numby Stuff (Iomed, Salt Lake City, UT) uses iontophoretic delivery of lidocaine with epinephrine using an impregnated electrode, current generator, and a return pad. It provides dense cutaneous analgesia in about 8 minutes ( Zempsky et al., 1998 ;Schultz et al., 2001 ). Another interesting delivery system, the Epiture Easytouch (Norwood Abbey, Victoria, Australia), uses a single-pulse Er:YAG laser to remove the stratum corneum layer of skin. One then applies 4% liposomal lidocaine cream and cutaneous analgesia is achieved in 5 minutes ( Baron et al., 2003 ). Both of these techniques are limited by the relatively high cost of each individual application.


PCA is a common and effective method of analgesia for postsurgical pain management in children, adolescents, and adults ( Berde and Sethna, 2002 ). The rationale for PCA analgesia is that the usual doses of as-needed (PRN) medication can lead to episodes or cycles of pain, followed by rescue dosing that causes excessive sedation and other opioid side effects. More frequent, smaller doses of opioids, which can be self-administered by the patient, lead to better analgesic titration with fewer side effects. The child's control over his or her own analgesia has considerable psychological benefits and allows him or her to anticipate increased activity, such as physical therapy or pulmonary toilet maneuvers ( McKenzie et al., 1997 ). A controlled opioid delivery system also eliminates the need for the nurses to sign out controlled substances and the need to administer the medication ( Kho and Thomas, 1994 ; Chan et al., 1995 ; Colwell and Morris, 1995 ). PCA is safe and effective in children as young as 5 years ( Berde et al., 1991 ) and compares well with continuous morphine infusions in the older child ( Bray et al., 1996 ). There have been occasional reports of children as young as 2 using PCA devices effectively ( Rusy et al., 1997 ). PCA technology can be safely used in children younger than 5 years, using a basal infusion with parents or nurses delivering the bolus doses ( Monitto et al., 2000 ). Characteristics of maturity, computer dexterity, family and nursing support, and patient familiarity with the hospital environment can be good predictors of successful use of PCA at such a young age. Adaptable PCA control buttons are helpful for the patient with cerebral palsy, who can understand the concept of PCA but may not have the manual dexterity to use the typical small button to activate the machine.

Parent- and nurse-controlled analgesia is another way to use PCA technology, when the patient is incapable of delivering doses, due to either immaturity, developmental delay, or medical condition. This technique often uses a higher level of basal infusion with a longer lockout time for individual doses ( Lloyd-Thomas, 1995 ; Monitto et al., 2000 ). Instruction and strictly set guidelines are needed when parents are activating the PCA, as they are often emotionally involved in the care of the patient and need to understand safety features of the PCA. This technique has been used successfully for many years with specific attention to the rule that no bolus doses may be administered if the child is asleep or drowsy. This attempts to recapitulate the intrinsic safety features of self-administered PCA. This approach is considered to be a safe and well-accepted form of analgesia ( Monitto et al., 2000 ).

It is important to initiate PCA in the recovery room or the emergency department to avoid the potential long delay in obtaining the PCA device by the floor nurse, obtaining the proper medication, and then programming the device ( Table 13-10 ). Typical starting doses of morphine are 0.01 to 0.02 mg/kg, every 6 to 10 minutes, with an hourly maximal dose of 0.1 to 0.15 mg/kg. A low-dose background infusion of 0.004 mg/kg per hour was reported as useful, in the first 24 hours, and shown to improve sleep patterns without increasing the adverse effects seen with higher background infusions in children (Doyle et al., 1993 ). Others advocate basal infusions that are somewhat more generous (0.01 to 0.02 mg/kg per hour) ( Berde et al., 1991 ). In studies comparing three methods of administering morphine'intramuscularly, PCA alone, and PCA plus low-dose basal ( Berde et al., 1991 )'it was noted that the best analgesia and greatest patient satisfaction occurred with PCA and with low-dose basal infusion. Other opioids can be used in instances where there is morphine sensitivity or intolerance. Hydromorphone, meperidine, and fentanyl can be administered with PCA ( Yaster et al., 1997 ) (see Table 13-10 ).

TABLE 13-10   -- Patient-controlled analgesia (PCA) doses


PCA Dose (mg/kg per dose)

PCA Hourly Maximum (mg/kg)

Basal Rate (mg/kg per hour)

Registered Nurse–Administered Additional Bolus (mg/kg) for Pain (Above Basal/Doses Administered)


0.01 to 0.03


0.01 to 0.03

0.05 to 0.1


0.002 to 0.006


0.002 to 0.006

0.01 to 0.02


0.0005 to 0.002 (0.5 to 2 mcg/kg per dose)

0.0035 to 0.005 (3.5 to 5 mcg/kg per hour)

0.001–0.004 (1 to 4 mcg/kg per hour)

0.001 to 0.002 (1 to 2 mcg/kg)

*Load with 0.5 to 1 time hourly max if no opioid in >2 hours. Lockout: 6 to 10 min for patient; 8 to 12 min for parent/registered nurse. Consider setting the PCA dose equal to the hourly basal rate. Adjust up for pain by increments of 10% to 20% in both doses.

For patients not well controlled, consider adding a basal, increasing dose or basal by 10% to 20% after an additional bolus is given.




An exciting new PCA system has been described for postoperative pain control in adults. This system uses a credit card–sized iontophoretic delivery system that uses fixed-dose fentanyl ( Gupta et al., 1998). Two separate trials have been reported in adults that demonstrate excellent tolerability, side effects, and analgesia with this system ( Chelly et al., 2004 ; Viscusi et al., 2004 ). The technique does not require intravenous access and analgesia is achieved rapidly, due to the excellent skin penetration of iontophoretic fentanyl.


Continuous infusion of opioids is a means of managing postoperative pain in infants and young children unable to use a PCA device. Morphine dosages of 0.02 to 0.03 mg/kg per hour can provide consistent levels of analgesia with minimal respiratory depression ( Bray, 1983 ; Bray et al., 1986 ; Bosenberg, 1988 ). Bray and others ( Bray et al., 1996 ; Bray et al., 1996 ; Lynn et al., 2000 ) have also demonstrated analgesic efficacy similar to PCA in various pediatric populations. This technique may be the preferred method of morphine delivery in the hospitalized child with moderate or severe pain.


Epidural analgesia is another way to approach acute postoperative pain management in the pediatric patient ( Table 13-11 ). Pulmonary function may be enhanced with effective epidural analgesia after upper abdominal surgery and thoracic procedures in pediatric patients ( Tyler, 1989 ). Murrell and others (1993) reported that in neonates undergoing primary abdominal procedures, prolonged postoperative ventilation could be avoided by combining general anesthesia with epidural analgesia. Epidural analgesia is associated with a lower incidence of postoperative respiratory depression and cardiovascular complications compared with intravenous opioids ( Wolf et al., 1993 ). Continuous lumbar epidural analgesia has been reported to decrease the incidence of bladder spasm in patients undergoing ureteral reimplantation surgery ( Park et al., 2000 ). McNeely and others (1997) studied high-risk pediatric patients undergoing gastric fundoplication procedures and showed that the complication rate was decreased in those receiving epidural versus intravenous opioid techniques. Patients in the epidural group were discharged earlier from the intensive care unit and the hospital ( McNeely et al., 1997 ).

TABLE 13-11   -- Doses of epidural analgesics







Epidural Loading Doses

Epidural Infusion (mL/kg per hour)

PCEA Dose (mcg/kg/dose)

Onset (min)

Duration (hr)

Discontinue Monitors (hr)

Discontinue Foley (hr)

Give IV or PO Analgesics

Infants younger than 6 mo or patients at risk for respiratory depression

Morphine 10 mcg/mL + 1/16% bupivacaine

10 to 30 mcg/kg + 0.3 to 0.5 mL/kg (0.25%)

0.1 to 0.3


20 to 30

6 to 12



As soon as patient experiences discomfort

Hydromorphone 3 mcg/mL + 1/16% bupivacaine

1 to 3 mcg/kg +0.3 to 0.5 mL/kg (0.25%)

0.1 to 0.3



4 to 6



As soon as patient experiences discomfort

Fentanyl 1 mcg/mL + 1/16% bupivacaine

0.5 to 1 mcg/kg + 0.3 to 0.5 mL/kg (0.25%)

0.1 to 0.2 (neonates; < 6 mo; tip at site)



2 to 3



As soon as patient experiences discomfort

Morphine 20 mcg/mL + 1/16% bupivacaine

25 to 50 mcg/kg + 0.5 to 1 mL/kg (0.25%)

0.1 to 0.3

1/6 to ¼


6 to 12



As soon as patient experiences discomfort

Hydromorphone 5 to 10 mcg/mL + 1/16% bupivacaine

5 to 10 mcg/kg + 0.5 to 1 mL/kg (0.25%)

0.1 to 0.3

1/6 to ¼ hourly rate


4 to 6


2 to 4

As soon as patient experiences discomfort

Fentanyl 2 mcg/mL + 1/16% bupivacaine

1 to 2 mcg/kg + 0.5 to 1 mL/kg (0.25%)

0.1 to 0.3

1/6 to ¼ hourly rate


2 to 3

0 to 2

0 to 2

As soon as patient experiences discomfort

Note: Maximum dosage for bupivacaine is 0.2 mg/kg per hour in newborns (0.4 mg/kg per hour in older infants and children).

Thoracic epidural doses should be at the lower end of these ranges (0.1 to 0.15 mL/kg per hour maximum).

Morphine dose is usually between 3 and 5 mcg/kg per hour; may be increased if patient is not overly sedated.

Ropivacaine may be substituted for bupivacaine. Consider loading with 0.2% and using 0.1% for infusions.

Clonidine may be added to any of these solutions. Consider using 1 mcg/mL and reducing the opioid dose by 50%. Also consider loading with 1 mcg/kg and reducing the original opioid load by 50%. AVOID CLONIDINE IN NEONATES (APNEA).

For patients who are not well controlled, consider a bolus equal to the volume of 1 hour basal infusion and then increase the rate by 20%. If there is a question of whether the epidural is working, test with 3 to 5 mg/kg lidocaine (0.5% to 1%). If there is no block, D/C epidural and change pain therapy.

Avoid testing with bupivacaine (0.25%) as inadvertent intravascular administration can lead to cardiovascular collapse.




Single-shot caudal analgesia with bupivacaine is very safe, can last as long as 6 to 8 hours, and has been effectively used for outpatient procedures such as inguinal hernia repair and orchidopexy ( McGown, 1982 ; Broadman et al., 1987 ; Dalens and Hasnaoui, 1989 ) (see Chapter 14 , Regional Anesthesia). Others have also reported substituting ropivacaine, which may provide less risk of cardiovascular compromise from inadvertent vascular injection ( Ivani et al., 1998 ; Khalil et al., 1999 ; Luz et al., 2000 ). The addition of epidural opioids provides longer-lasting analgesia but adds the potential for respiratory depression. Consequently, patients receiving caudal or epidural opioids should be monitored in the hospital ( Krane, 1988 ; Krane et al., 1989 ; Karl et al., 1996 ).

The epidural space can be approached at any level: caudal, lumbar, or thoracic. Most children can have the epidural space accessed with 18- or 20-gauge Touhy or Crawford needles and a saline technique for loss of resistance (see Chapter 14 , Regional Anesthesia). Air should be avoided in children to avoid the risk of air embolus, if a patent foramen ovale, a ventricular septal defect, or an atrial septal defect is present ( Williams et al., 1991 ). In addition, in small infants, epidural catheters can be threaded from the caudal space to even thoracic levels ( Bosenberg et al., 1988 ; Gunter and Eng, 1992 ). Tucker and Mather (1975) demonstrated that the epidural fat of infants has a spongy gelatinous quality with distinct spaces found between fat lobules. The location of the catheter tip is best placed at the dermatome where the surgery is to occur. This can be accomplished by approaching the epidural space at the level of the surgical incision. Alternatively, a radiopaque catheter can be used so that the location can be checked by radiograph. If the catheter is not plainly visible, water-soluble dye can be used to identify the catheter and the exact location of the tip. Tsui and others (Tsui et al., 1998, 1999 [354] [355];Goobie et al., 2003 ) described a novel technique to determine catheter tip location of caudally advanced epidural catheters. This technique uses a low current nerve stimulator to detect muscle twitches as the catheter is advanced to its final destination.

Epidural catheters inserted below the first or second lumbar vertebra offer the safety feature of being below the termination of the spinal cord. However, the delivery of the epidural solution several dermatomes well below a thoracic surgical procedure may result in inadequate analgesia. Caudle and others (1993) showed that patients with thoracic epidural catheters placed for thoracic or upper abdominal procedures had better pain relief than did patients with lower catheters. Because of the potential difficulties of placing catheters in awake, young pediatric patients, it has been the standard of care for many years among pediatric anesthesiologists to place epidural catheters in anesthetized patients ( Krane et al., 1998 ). Giaufré and others (1996) preformed the largest prospective study evaluating the morbidity of regional anesthesia in anesthetized children. There were 24,409 regional blocks performed in patients between 3 and 12 years of age: 15,013 were caudal blocks, 5215 were nerve blocks, 506 were spine blocks, and 135 were thoracic epidurals. Local infiltration accounted for all of the other blocks. There were 23 complications, 4 total spinal blocks, 6 intravascular injections with convulsions in 2 and cardiac arrhythmias in 2, and 2 transient paresthesias. More than half of the complications may have been influenced by the patient's alertness during performance of the block and none of the sequelae were long term (see Chapter 14 , Regional Anesthesia).

To minimize the side effects of epidural analgesia, a combination of local anesthetic and opioids is used to permit using a lower dose of each agent. Morphine, fentanyl, and hydromorphone are frequently combined with 0.0625% to 0.1% bupivacaine. Standardized concentrations of these mixtures allow the pharmacy to have premixed bags readily available. Epidural infusions can be set up as epidural PCA, in which the patient or registered nurse can administer additional doses for breakthrough pain ( McDonald and Cooper, 2001 ; Molik et al., 2001 ; Lin, 2002 ; Birmingham et al., 2003 ; Hansen et al., 2004 ). All patients are administered epidural bupivacaine, with the opioid of choice, at the start of the operation with consideration of a repeat dose, if an appropriate amount of time has elapsed. In general, fentanyl can be reloaded every 4 hours, whereas redosing of morphine or hydromorphone depends on the amount initially administered and the elapsed time. In general, redosing is not needed for procedures that take less than 6 to 8 hours. Bupivacaine can be redosed every 1 to 2 hours, using about half of the initial loading dose, so that a denser block can be maintained intraoperatively.

When the catheter tip is close to the dermatome of surgery, fentanyl is the opioid of choice. When the tip is farther from the site of the operation, such as a lumbar catheter in a patient who underwent a thoracotomy, more water-soluble opioids, such as morphine and hydromorphone, are chosen to have the desired spread. The morphine load is usually 30 to 50 mcg/kg, hydromorphone is 3 to 5 mcg/kg, and fentanyl is 0.5 to 2 mcg/kg. Infusion rates of the bupivacaine must be kept below 0.2 mg/kg per hour in the neonate and infant under 4 to 6 months of age and below 0.4 to 0.75 mg/kg per hour in the child over 2 years of age to avoid toxicity and cardiovascular instability ( McCloskey et al., 1992 ; Wood et al., 1994 ; Luz et al., 1996, 1998 [228] [231]). Adjuvant NSAIDs (ketorolac, etc.) can also be safely used with epidural analgesia.

Contraindications to placement of an epidural catheter include intrinsic coagulopathy or use of anticoagulants, sepsis, and infection in the skin at the site of insertion. Relative contraindications might include neurologic disease such as multiple sclerosis. Infection from epidural catheters for postsurgical pain management in pediatric patients is rare ( Strafford et al., 1995 ; McNeely et al., 1997 ). However, it may occur when epidural catheters are tunneled in terminally ill patients for long-term pain management and needs to be aggressively monitored and treated if diagnosed ( DuPen et al., 1987 ).

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Copyright © 2005 Mosby, An Imprint of Elsevier


Chronic pain has become a significant problem in the pediatric population, conservatively estimated to affect 10% to 15% of the population ( Goodman and McGrath, 1991 ). Signs of sympathetic nervous system arousal rarely accompany chronic pain, in contrast to acute pain. The lack of objective signs may prompt the inexperienced clinician to say the patient “does not look like he or she is in pain” (American Pain Society, 2003 ). Signals of facial grimacing, limping, and tachycardia may be absent in the chronic pain patient. There is no neurophysiologic or chemical test that can measure pain; the clinician must accept the patient's report of pain. The International Association for the Study of Pain (IASP) classifies chronic pain as less than 1 month, 1 to 6 months, and greater than 6 months ( Merskey and Bogduk, 1994 ). Formerly, chronic pain was defined as having pain for longer than 6 months, but it is now recognized that chronic pain can be evident much earlier.

Patients with chronic pain can include children with headaches, myofascial pain, chronic abdominal pain, complex regional pain syndrome, cancer pain, phantom limb pain, cerebral palsy, arthritis, and sickle cell anemia ( Box 13-2 ). These patients have significant alterations in their lifestyles; often have poor school attendance and social withdrawal. The entire family is affected significantly by the pain condition. Most child health specialists have limited experience in treating patients with chronic pain, and pediatric textbooks offer little guidance. Some patients move from one physician to the next, even to different cities or states, and almost all have undergone extensive medical testing that has been costly and often revealed little or no insight into what the problem may be.

BOX 13-2 

Pediatric Chronic Pain


Chronic abdominal pain, functional abdominal pain

Irritable bowel syndrome

Crohn's disease, ulcerative colitis

“Growing pains”

Myofascial pain


Juvenile rheumatoid arthritis

Sports injuries

Complex regional pain syndrome

Phantom limb pain

Sickle cell anemia


Cerebral palsy


Chronic pain can be differentiated from acute pain in that acute pain signals a specific nociceptive event and is self-limited. Chronic pain may start out as an acute event but continues beyond the normal time expected for recovery. Chronic pain in children is a result of a dynamic integration of biologic processes with contributing psychological factors, sociocultural factors, and developmental and family dynamics. To evaluate and treat chronic childhood pain effectively and efficiently, a multidisciplinary approach is most successful, incorporating physicians with nurses, psychologists, psychiatrists, physical therapists, social workers, and occupational therapists. The mind–body dualism must be abandoned. To continue to think that pain is associated with a single physical cause can result in the physician investigating the patient with repeated invasive testing, laboratory tests, and procedures and lead to overprescription of medications. One needs to acknowledge the patient's multidimensional experience of pain and treat it from the various angles to which each participant in the multidisciplinary team can contribute.


The evaluation of a patient with chronic pain should begin with a complete history, where all members of the multidisciplinary team participate ( Box 13-3 ). Factors to investigate include the pain itself; the time frame for the painful condition; the descriptors of the pain, such as sharp, dull, burning, throbbing, or pounding; and what helps or exacerbates the pain. One should find out how it has affected the patient's activities of daily living such as sleep, exercise, nutrition, family relations, and school attendance. It is important to determine what, if any, therapies have afforded some degree of relief. Assessment should include what the family perceives as causing the pain and how they have responded to it. Family history of chronic pain problems should be investigated. One should review whether alternative forms of pain therapies have been tried. The review of systems should pay special attention to possible symptoms of depression. Social history of how the pain problem has affected the family structure, including who lives at home, how the patient is doing in school, and the parents' vocations and work status, should be clarified. Recent stressors should be identified, including a death in the family, parental separation or divorce, or a move. Frequently, the chronic pain patient has missed a considerable amount of school and extracurricular activities.

BOX 13-3 

Recommended Staff for Multidisciplinary Pain Management Center

Pain specialist physician

Pediatric psychologist

Consulting psychiatrist

Advanced practice nurses

Pediatric physical/occupational therapist

Social worker

Administrative assistants

All members of the team may interview the family and patient together to obtain the medical and pain history (see Box 13-3 ). The psychologist or therapist then interviews the parents alone while the physician is performing the physical evaluation in collaboration with the advanced practice nurse and physical or occupational therapist. The psychologist then meets briefly and alone with the patient. The members of the team gather and formulate a plan of treatment. The plan is then presented to the family and patient with the entire team present. A written summary of the plan is given to the family during this exit session. It includes, as appropriate, a combination of pharmacologic, physical, and occupational therapy interventions; massage therapy; acupuncture; cognitive-behavioral pain strategies including meditation, deep relaxation, guided imagery techniques, and mindfulness meditation; and individual and/or family counseling. Patients are also counseled on how nutrition, sleep habits, and exercise can play a role in their pain condition. Major goals are established to improve psychological functioning (decreased school absences); psychological support for the entire family and communication with both the patient's school and physician can occur. When elimination of pain is likely not to occur with a simple intervention, efforts focus on modulating the pain to tolerable levels, allowing there to be return to school (even if part time) and return to participation in activities with friends and family. The time course of such an intake evaluation is about 90 minutes, and most patients are then seen over a period of 1 to 6 months to accomplish these goals.


As many as 20% of children younger than 5 years have headache as a common chronic pain complaint ( Sillanpaa et al., 1991 ). In another report, 10% to 20% of children younger than 10 years complained of headache ( Carlsson, 1996 ). At puberty, migraine headaches become common with 10% to 27% of adolescent girls and 4% to 20% of adolescent boys reporting them ( Abu-Arafeh and Russell, 1993 ). Approximately 60% of children who have migraines continue to have migraines as adults ( Bille, 1997 ). Tension-type headache is also a highly prevalent condition that can be quite disabling ( Schwartz et al., 1998 ).

Evaluation of the patient is performed as described earlier and includes a detailed neurologic evaluation. Virtually every headache patient seen in a chronic pain clinic has had prior neuroimaging with, most commonly, magnetic resonance imaging (MRI), to rule out brain tumors, vascular anomalies, and other structural abnormalities. Ophthalmological, dental, and sinus conditions, especially potential infections, should not be overlooked. Burton and others (1997) reviewed the etiology of headaches in children presenting to an emergency department. Thirty-nine percent had headache associated with a viral illness; an equal number (16%) had sinusitis and migraine. In addition, temporomandibular joint dysfunction can result in recurrent bitemporal headaches ( Reik and Hale, 1981 ).

Treatment approaches include medications for both preventative and abortive therapy, including NSAIDs, acetaminophen, TCAs, SSRIs, ergotamines, β-adrenergic blockers, or triptans. The occasional use of opioids to abort a refractory headache may be indicated. One of the most important components of any chronic headache treatment program is cognitive-behavioral therapy; this may include biofeedback ( Gauthier et al., 1981 ; Saeed et al., 1992 ; Silberstein, 2000 ), relaxation techniques, cognitive reframing, and a variety of standard psychotherapeutic interventions ( Reid and McGrath, 1996 ; Grazzi et al., 1998 ). Simple home-based therapy with minimal therapist contact can be effective in headache management ( Rowan and Andrasik, 1996) . A complete review of this topic is presented in recent reviews of the subject by Larsson (1999) and McGrath and Hillier (2001) .


Recurrent abdominal pain was defined many years ago as pain occurring at least once per month for 3 consecutive months ( Apley and Naish, 1958 ). The pain is usually periumbilical, lasting 1 to 3 hours, and may be associated with pallor, vomiting, sweating, and nausea. Sleep patterns may be disturbed. Although it is important for physicians to exclude organic illness, almost all studies have found that only 10% of children with recurrent abdominal pain have recognizable organic illness accounting for the pain complaints ( Apley and Naish, 1958 ; Saavedra and Perman, 1989 ). Organic causes include ulcer, lactose intolerance, ulcerative colitis, infection (Helicobacter pylori), and Crohn's disease. Once organic causes are excluded, it is important to communicate to the family that even though an organic cause cannot be found, the treating medical personnel believe the pain is real and attempts must be made to manage it. There is some evidence that these patients may have forms of irritable bowel syndrome with associated visceral hyperalgesia ( Di Lorenzo et al., 2001 ; Alaradi and Barkin, 2002 ). Animal models have confirmed that in a variety of stimulus models, abnormal responses to colonic or rectal stimulation can be elicited ( Kamp et al., 2003 ; Palecek and Willis, 2003 ; Gaudreau and Plourde, 2004 ; Miranda et al., 2004 ). These animals demonstrate central sensitization, possibly mediated by NMDA receptor activity. These studies, plus several others in adult patients with irritable bowel syndrome ( Delvaux, 2002 ; Hunt and Tougas, 2002 ; Verne and Price, 2002 ; Verne et al., 2003) , lend support to the notion that even without clear-cut pathologic findings, patients can have persistent abdominal pain syndromes. Again, a multidisciplinary approach is taken, incorporating medications (COX-2 inhibitor, NSAIDs, TCAs, tramadol, or SSRIs); behavioral approaches to manage stress and anxiety; sleep hygiene, biofeedback training, and encouragement of return to normal activities. There is some evidence that these patients respond to amitriptyline ( Jailwala et al., 2000 ; Huertas-Ceballos et al., 2002a , 2002b). The reader is referred to recent reviews on this subject by Walker (1999) and Hyams and others (1999 , 2002 [176] [177]).


Myofascial pain or fibromyalgia is characterized by widespread pain, multiple tender points on physical examination, fatigue, sleep difficulties, abdominal pain, headaches, and mood disturbance and is estimated to occur in 1% to 6% of the juvenile population ( Kashikar-Zuck et al., 2002 ). In 1985, Yunus and Masi (1985) described the juvenile primary fibromyalgia syndrome ( Table 13-12 ). Malleson and others (1992) reported that, using these diagnostic criteria, a significant percentage of children showed no improvement in symptoms when followed for more than 2 years. Current management includes improving sleep hygiene, regular physical activity (aerobic exercise), cognitive-behavioral strategies, and low-dose TCAs to improve both pain and sleep disturbance ( Breau et al., 1999 ). Acupuncture is another form of therapy that, on a regular basis, can be very beneficial in controlling muscle tender points ( Sprott et al., 1998 ).

TABLE 13-12   -- Juvenile primary fibromyalgia syndrome

Major Criteria

Minor Criteria



General musculoskeletal aching at 3 or more sites for 3 or more months in the absence of any underlying condition



Normal laboratory tests



Severe pain in 5 of 18 bilateral tender point sites with palpation of less than 4-kg force: occiput; low cervical area; trapezius; supraspinatus; second rib; lateral epicondyle; gluteal, upper outer quadrant of buttock; greater trochanter; knee



Subjective soft tissue swelling



Pain modulated by physical activities



Pain modulated by weather factors



Pain modulated by anxiety/stress



Irritable bowel syndrome



Chronic anxiety or tension






Poor sleep






Chronic headaches

Diagnosis is based on ALL 3 major criteria plus 3 of 10 minor criteria OR 1 and 2 plus 4 of 18 tender points and 5 of 10 minor criteria.

Modified from Yunus MB, Masi AT: Juvenile primary fibromyalgia syndrome. A clinical study of thirty-three patients and matched normal controls. Arthritis Rheum 28:138–145, 1985. (Copyright © 1985. Reprinted with permission of Wiley-hiss, Inc., a subsidiary of John Wiley & Sons, Inc.)





Complex regional pain syndrome (CRPS) refers to a syndrome of persistent neuropathic pain associated with nondermatomal autonomic dysfunction. It often is seen after minor injury, and patients have findings that include temperature and color changes, allodynia, edema, cyanosis, eventual trophic changes of the skin, and osteoporotic changes, if left untreated. The current IASP diagnostic criteria (published by Stanton-Hicks et al. [1995 ]) include (1) at least two neuropathic pain descriptors (burning, dysesthesias, paresthesias, mechanical allodynia, and hyperalgesia to cold) and (2) at least two physical signs of autonomic dysfunction (cyanosis, mottling, hyperhidrosis, >3°C lower temperature in affected limb, edema).

The cause of pain is not completely understood but is thought to be related to abnormal discharges in sympathetic afferent nerves along with nociceptive effects produced by the incidental trauma. Sensitivity of nerve receptors, spontaneous neuronal ectopy, and psychological components of the pain are always present. Ruggeri and others (1982) published data to show that CRPS in children is benign and responds to physical therapy. Others suggest that a subset of patients continue to have severe pain and disability ( Greipp and Thomas, 1987 ). Wilder and others (1992) published a report of 70 patients, who were predominately female, who had involvement of the lower extremity disease. Conservative treatment, including physical therapy, transcutaneous electrical nerve stimulation (TENS), TCAs, cognitive-behavioral therapies, and relaxation therapies, was used with some success. Two thirds of the patients in this series responded to sympathetic blockade. In a 2002 study by Lee and others, reduced pain and improved functioning were reported after a 6-week course of intensive physical therapy and cognitive-behavioral therapies without the need for sympathetic blockade. This approach does not incorporate any invasive regional nerve blockade but instead used neuromodulating drug therapy (TCAs with gabapentin or other antiepileptic agents) with intensive physical therapy, administered on a 3-day-per-week regimen up to even twice a day. In patients who were unable to tolerate this degree of physical therapy, anesthesia-monitored deep sedation with propofol has been used to allow manipulation of the affected extremity or extremities. Psychotherapy that includes a focus on cognitive-behavioral interventions plus intensive decatastrophizing of the illness is also used in the treatment of patients with CRPS. In addition, intensive family psychotherapy may be needed to restore intrafamily relationships that interfere with recovery. Except for a small proportion of patients who respond quickly to over-the-counter pain medications and increased physical activity of the involved extremity, CRPS type I is a disease that is best managed at a pediatric pain management center.


Sickle cell anemia is an inherited hemoglobinopathy that results in recurrent acute and chronic pain due to red cell sickling and obstruction of the microvasculature with subsequent embolism and inflammation. Painful vaso-occlusive episodes occur in the hands and feet, extremity long bones, chest, and abdomen, leading to frequent hospitalizations for intensive pain management with intravenous opioids. The recognition of pervasive undertreatment or inappropriate treatment prompted the American Pain Society to develop guidelines for pain treatment (1999). Chronic pain in sickle cell anemia can be associated with bony changes such as avascular necrosis of the femoral heads, vertebral collapse, and chronic, recurrent leg ulcerations ( Esseltine et al., 1988 ). The superimposition of unpredictable acute pain crises on top of chronic pain compounds the chronic pain assessment of these patients. It is imperative to complete a thorough evaluation of all the biologic and psychological aspects of the individual and his or her family and support system. Emotional support, possible chronic transfusions, hydroxyurea (to stimulate fetal hemoglobin production), and the selective administration of NSAIDs or TCAs, with liberal use of short- and long-acting opioids, can help the patient who has sickle cell crises.

Patients with sickle cell anemia often have used opioids for pain control and may even be managed on chronic, long-acting opioid medications, such as MS Contin (morphine sulfate), OxyContin (oxycodone), or methadone. They may have a high tolerance to opioid analgesics. In general, children with vaso-occlusive episodes consume more than twice as much morphine as children with postoperative pain ( Shapiro et al., 1993 ). Pseudo-addiction has been reported in patients with sickle cell disease ( Kirsh et al., 2002 ; Elander et al., 2004 ). In these patients, underprescription of adequate doses and amounts of analgesics leads to the expression of behaviors that are interpreted as drug seeking. A variety of sociocultural factors contribute to this syndrome of gross undertreatment of sickle cell pain.

Regional anesthesia may be a good choice to help manage a sickle cell crisis in the lower extremity or pelvis, including priapism. It may also be quite beneficial in the management of the acute chest syndrome. Epidural anesthesia with local anesthetics administered alone or in combination with fentanyl has been shown to effectively treat sickle cell vaso-occlusive crisis unresponsive to conventional methods with fewer side effects such as sedation or respiratory depression ( Yaster et al., 1994 ; Labat et al., 2001 ).


Cancer is the second leading cause of death in children after trauma. Almost all children who have cancer experience pain during the course of diagnosis, treatment, and end of life ( Miser et al., 1987 ). Children with cancer may have pain that can be classified into four broad categories: cancer-related pain (bone pain, neuropathic pain, somatic pain, terminal care); treatment-related pain from chemotherapy, radiation, infection, and phantom limb pain; procedure-related pain; and pain unrelated to the cancer (preexisting pain such as headache, trauma, or other medical problems such as appendicitis). Children who survive cancer rate the pain from procedures and treatment as worse than pain related to the cancer itself ( Fowler-Kerry, 1990 ). In fact, in a survey of Swedish children with cancer, Ljungman and others (1999) found that almost 50% of reported pain was from treatment, 40% was from procedures, and only 10% was from the disease itself. For almost 15 years, cancer pain treatment has been guided by the World Health Organization Analgesic Ladder (1990). Mild pain can be treated with nonopioids first, with it kept in mind that these agents have a ceiling effect and side effects that include inhibition of platelet function, gastritis, and decreased renal blood flow. Moderate pain can be treated with an oral opioid plus the nonopioid. Severe pain can be managed with potent intravenous opioids. As it was originally proposed, the “ladder” suggests a progression of therapy that escalates as the patient fails the lowest rungs (Ljungman et al., 1996 , 1999 [225] [224]). However, a more appropriate conceptualization of the ladder demands selecting the analgesic agent that seems best matched to the severity of the patient's pain. In addition, some pain in cancer can be opioid resistant, such as spinal cord or nerve root compression from an intraspinal Ewing's sarcoma. In this case, the prompt addition of adjuvant analgesics such as the TCAs or gabapentin is indicated, even though these agents were not part of the original schema. Unless the individual has unusual, intermittent pain episodes, a regimen of around-the-clock, long-acting opioids (sustained-release morphine or methadone) should be chosen, with a short-acting, immediate-release agent available for breakthrough pain (immediate-release morphine or oxycodone). Patients unable to tolerate the oral administration of opioids can be managed with intravenous drugs, with either as-needed dosing, continuous infusions, or PCA.

Because patients with progressive malignancy may need chronic opioid therapy, it is important to titrate doses as needed. Fortunately, the opioid analgesics do not demonstrate an analgesic ceiling effect; it is not uncommon to encounter situations where massive doses of opioids are required to continue analgesia ( Collins et al., 1995 ; Sirkia et al., 1998 ). The majority of children can be successfully managed using oral or intravenous therapy, even through the end of life ( Ljungman et al., 1996 ). Although most children remain comfortable with moderate dosing, a subgroup of patients may require drastic escalation of dosing ( Collins et al., 1995 ). This is especially true in patients with solid tumors that have metastasized to nerves, the spine, or the central nervous system.

Under rare circumstances, terminally ill children with cancer may benefit from invasive neuraxial therapy delivered via an implanted intraspinal or epidural catheter ( Collins, 1996 ; Ljungman et al., 1996 ). Other invasive approaches to drug delivery, such as celiac plexus blockade ( Rykowski and Hilgier, 2000 ) or even neurosurgical ablations ( Cherny, 2000 ), are even less commonly used.

The key to the success of opioid pain management for cancer pain is incorporation of a careful plan for the management of side effects. Constipation is common, and regular stool softeners or laxatives are needed; enemas must usually be avoided in cancer patients due to the risk in causing perirectal infection by introducing bacteria into the bloodstream. Small doses of stimulants (methylphenidate, amphetamines, modafinil, or atomoxetine) may help combat sedation. Antihistamines and antiemetics are often also needed on an as-needed basis. Neuropathic pain secondary to metastasis or chemotherapeutic agents (e.g., vincristine) is common in these children and often requires management with TCAs, gabapentin, or TENS units ( Foley, 1995 ; Breitbart, 1998 ; Wiffen et al., 2000 ).

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Motoyama & Davis: Smith's Anesthesia for Infants and Children, 7th ed.

Copyright © 2005 Mosby, An Imprint of Elsevier


Traditionally, health care practitioners have approached pain management in children on an “either/or” basis'that is, pharmacologic interventions or “alternative” approaches. A multidisciplinary approach that combines several different modalities is best. Cognitive-behavioral approaches such as relaxation techniques, breathing exercises, TENS, biofeedback, and even acupuncture can augment any of the pharmacologic interventions ( Rusy and Weisman, 2000 ).


Children are highly responsive to pain-reducing strategies that involve their imagination and sense of play. Children younger than 6 years can be distracted by blowing bubbles, playing with pop-up toys, or looking through a kaleidoscope ( Zeltzer and Lebaron, 1982 ). Older children engage well in external or abstract interventions, such as guided imagery, counting, and breathing techniques ( Zeltzer and Lebaron, 1982 ; Kuttner, 1988 ; LeBaron et al., 1988 ; Chen et al., 2000 ). Preschoolers can imagine a superhero who can “turn off the pain switch” ( Kachoyeanos and Friedhoff, 1993 ). Zeltzer and Lebaron (1982) compared hypnotic and nonhypnotic techniques for reducing pain associated with bone marrow aspirations and lumbar punctures in children with cancer; hypnosis was found to be significantly better in reducing procedural distress. A potential physiologic explanation of the effectiveness of hypnosis in reducing pain is that hypnosis inhibits transmission of pain signals from peripheral fibers at the level of the dorsal horn ( Crawford et al., 1998 ). Alternatively, hypnosis may work by causing amnesia of the events surrounding the hypnotic trance.

Progressive muscle relaxation is designed to help children recognize and reduce tension associated with pain, decrease anxiety, and decrease discomfort. Learning to decrease body tension is an acquired skill, and relaxation training requires initial instruction and then frequent practice to be successful. An occupational therapist or a psychologist often teaches these skills. Biofeedback uses alpha-electroencephalography, muscle electromyography, skin temperature, and temporal pulse feedback to provide immediate information to allow a child to observe and modify the level of tension in the body (Andrasik and Attanasio, 1985 ; Williamson et al., 1988 ; Labbe and Ward, 1990 ; Finley and Jones, 1992 ; Labbe, 1995 ; Blanchard et al., 1997 ). These techniques can be very effective for the management of headache ( Andrasik et al., 1983 ; Daly et al., 1983 ; Druckro and Cantwell-Simmons, 1989 ; Engel and Rapoff, 1990 ; Labbe, 1995 ; Bussone et al., 1998 ), procedure pain ( Broome, 1984 ), and chronic abdominal pain ( Masek et al., 1984 ; Banez and Steffen, 2001 ; Weydert et al., 2003 ).


TENS can be an additive technique for pain management ( Long, 1978 ; Avellanosa and West, 1982 ; Meyler et al., 1994 ). A TENS unit generates a nonpainful stimulus at peripheral nerves and appears to facilitate the closing of the gate for transmission of pain. TENS may stimulate the body to produce endorphins, that then act as natural painkillers ( Chapman and Benedetti, 1977 ; Mannheimer and Carlsson, 1979 ; Hughes et al., 1984 ; O'Brien et al., 1984 ; Facchinetti et al., 1986 ). In fact, several investigators have demonstrated that opioid antagonists can reverse the effect of TENS ( Chapman and Benedetti, 1977 ; Mannheimer and Carlsson, 1979 ). TENS is useful in management of many pain problems, including acute pain after chest surgery ( Cotter, 1983 ), fibromyalgia ( Stone and Wharton, 1997 ), chronic knee pain ( Jensen et al., 1986 ; Meyler et al., 1994 ; Ng et al., 2003 ; Breit and Van Der Wall, 2004 ), and cancer pain ( Avellanosa and West, 1982 ).


Acupuncture is among the most commonly used forms of complementary medicine for various pain problems. Acupuncture may provide analgesia through a mechanism similar to TENS. Stimulation of small pain fibers may inhibit spinal transmission of other pain signals ( Wang et al., 1992 ). Similarly, there is emerging evidence that through stimulation of the acupuncture energy channels, intrinsic opioid pathways are activated, causing profound analgesia ( He et al., 1985 ; He, 1987 ; Kho et al., 1993 ; Pintov et al., 1997 ). The National Institutes of Health found promising results in the use of acupuncture for the treatment of tennis elbow, myofascial pain, dental pain, stroke rehabilitation, and postoperative or chemotherapeutic nausea (1998). Zeltzer and others (2002) conducted a phase I investigation examining the acceptability of using acupuncture for chronic pediatric pain management and found significant improvement in pain measures. A retrospective case study on pediatric pain patients' experience with acupuncture revealed that 67% of children aged 5 to 18 years (median age, 16 years) rated their experience as positive or pleasant, and 70% of patients thought that the acupuncture helped the pain associated with headaches, endometriosis, or CRPS ( Kemper et al., 2000 ). Lin and others (2002) found that acupuncture significantly reduced pediatric pain associated with headaches, limb pain, chest pain, and abdominal pain when used in a multimodal approach to pain. Acupuncture is an exciting “new” technology that seems well tolerated by children, despite their general needle phobia, and now there is preliminary evidence of effectiveness for our young patients.

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Motoyama & Davis: Smith's Anesthesia for Infants and Children, 7th ed.

Copyright © 2005 Mosby, An Imprint of Elsevier


We have the tools to clearly understand the neurophysiology of pain transmission in children and ways to measure the amount of pain that a child is experiencing. Pain should be managed using a broad range of demonstrated tools that include pharmacologic, regional anesthetic, behavioral, and alternative therapies. Acute and chronic pain can be best handled when they are approached in a multidisciplinary fashion. Pediatric anesthesiologists can be active members of hospital-based acute pain services, as well as members of teams evaluating children with chronic pain. Ideally, centers will build multidisciplinary pain teams where physicians, nurses, physical therapists, and psychologists can assess pain and incorporate the various forms of therapy that were discussed in this chapter.

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Motoyama & Davis: Smith's Anesthesia for Infants and Children, 7th ed.

Copyright © 2005 Mosby, An Imprint of Elsevier


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