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Despite advances in neonatal pain assessment and manage-ment, nonpharmacologic and pharmacologic analgesic therapiescontinue to be underutilized to manage both acute and pro-cedural pain (Johnston et al, 1997; Simons et al, 2003a).Untreated acute, recurrent, or chronic pain related to diseaseor medical care may have significant and lifelong physiologicand psychologic consequences. As with all other medicalconditions, the first step in the treatment process is theaccurate diagnosis of the problem. Thus pain assessment pro-vides the foundation for all pain treatment. This chapterreviews the developmental neurophysiology of pain, discussesmethods to assess pain in infants, highlights factors thatinfluence the pain experience, and discusses evidence-basedstrategies for managing infant pain.

DEFINING PAIN AND DISTRESS IN INFANTSAND CHILDRENPain is defined by the International Association for the Studyof Pain (IASP) as “an unpleasant sensory and emotionalexperience associated with actual or potential tissue damage or described in terms of such damage” (Merskey, 1979). TheIASP definition also states that pain is always subjective and is learned through experiences related to injury in early life.This definition is problematic when considering infants whoare incapable of self-report and who may not have had previousexperience with injury. Anand and Craig (1996) propose thatpain perception is an inherent quality of life that appears earlyin development to serve as a signaling system for tissue damage.This signaling includes behavioral and physiologic responses,which are valid indicators of pain that can be inferred byothers. Broadening the definition of pain to include behavioraland physiologic indicators in addition to self-report can benefit preverbal, nonverbal, or cognitively impaired individualswho are experiencing pain by providing objective painassessment.

DEVELOPMENTAL NEUROPHYSIOLOGY OF PAINThe basic mechanisms of pain perception in infants and childrenare similar to those of adults and include (1) transduction andtransmission; and (2) perception and modulation. However,because of neurophysiologic and cognitive immaturity, somedifferences exist. A brief review is presented here and empha-sizes the developmental and maturational changes that occurduring infancy and childhood (Fitzgerald & Anand, 1993).

Peripheral Transduction and TransmissionNoxious mechanical, thermal, or chemical stimuli exciteprimary afferent fibers that transmit information about the

potentially injurious stimuli from the periphery to the dorsalhorn of the spinal cord. A-delta (large, myelinated, and fast-conducting) and C (small, unmyelinated, and slow-conducting)fibers are primarily responsible for pain impulse transmission(nociception). However, these signals can be amplified orattenuated by activation of surrounding neurons in the periph-ery and spinal cord. For example, tissue injury causes therelease of inflammatory mediators (e.g., potassium, bradykinin,prostaglandins, cytokines, nerve growth factors, catecholamines,and substance P) that sensitize A-delta and C fibers and recruitother neurons (silent nociceptors) and result in hyperalgesia.Stimulation of A-beta fibers that signal nonpainful touch andpressure can compete with the transmission of nociception inthe dorsal horn of the spinal cord, thus reducing the intensityof the perceived pain.

Central Mechanisms and ModulationNeurotransmitters in the spinal cord either amplify (e.g.,substance P, calcitonin gene-related peptide, neurokinin A) orattenuate (e.g., endogenous opioids, norepinephrine, serotonin,GABA, glycine) pain information from the periphery. Centralsensitization occurs when excitatory amino acids act onNMDA receptors to induce prolonged depolarization andwindup.

Nociceptive sensory input reaches the thalamus throughsecond-order neurons in the spinothalamic, spinoreticular, andspinomeosencephalic tracts and is then widely distributedthroughout the brain. The perception, emotional inter-pretation, and cognitive meaning of nociceptive stimuli occurwithin a distributive neuromatrix; no one “pain center” exists.The sensory-discriminative, affective-motivational, and eval-uative dimensions of pain perception are mediated by pastexperience and the context of the painful event. For example,nociceptive stimuli activate areas of the limbic system thoughtto control emotion, particularly anxiety. Thus differences inphysiologic, biochemical, and psychologic factors influencethe perception of pain, making it an individual phenomenon.

Descending modulation occurs when efferent projectionsfrom supraspinal areas such as the periaqueductal grey, raphenucleus, and locus coeruleus release inhibitory neurotrans-mitters. The major neurotransmitters that mediate descendinginhibition are norepinephrine, serotonin, endogenous opioids,GABA, and acetylcholine.

Neurodevelopment of Pain PerceptionInfants, even prematurely born infants, have the neurologiccapacity to perceive pain at birth (Fitzgerald & Anand, 1993).The peripheral and central structures necessary for nociception

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are present and functional early in gestation (between the firstand second trimesters). Functional maturation of the fetalcerebral cortex has been demonstrated by: (1) electroen-cephalogram (EEG) patterns and cortical evoked potentials;(2) measurement of cerebral glucose use that shows maximalmetabolic rates in sensory areas of the brain; and (3) well-defined periods of sleep and wakefulness that are regulated bycortical functioning from 28 weeks of gestation. The newborninfant possesses a well-developed hypothalamic-pituitary-adrenal axis and can mount a fight-or-flight response with therelease of catecholamines and cortisol.

Research suggests that some differences in nociceptiveprocesses between infants and adults exist. For example, painimpulse transmission in neonates occurs primarily alongnonmyelinated C fibers rather than myelinated A-delta fibers.Less precision also occurs in pain signal transmission in thespinal cord, and descending inhibitory neurotransmitters arelacking (Fitzgerald & Anand, 1993). Thus young infants mayperceive pain more intensely than older children or adultsbecause their descending control mechanisms are immatureand thus limit their ability to modulate the experience.

Pathophysiology of Acute PainAlthough pain can serve as a warning of injury, the effects ofpain are generally deleterious. Pain evokes negativephysiologic, metabolic, and behavioral responses in infants(Anand, 1998). These responses include increased heart rate,respiratory rate, and blood pressure and increased secretion ofcatecholamines, glucagon, and corticosteroids. The catabolicstate induced by acute pain may be more damaging to infants,who have higher metabolic rates and fewer nutritional reservesthan adults. Pain leads to anorexia and causes poor nutritionalintake, delayed wound healing, impaired mobility, sleepdisturbances, withdrawal, irritability, and developmentalregression. Premature infants who underwent cardiac surgeryand who received less anesthesia had more postoperativecomplications (Anand & Hickey, 1992), and prolonged painmay increase neonatal morbidity and mortality (Anand, 1998;Anand et al, 1999).

Learning about pain occurs with the first pain experienceand has profound effects on subsequent pain perception andresponses. Memory of pain in infants is evident fromdifferences in responses to painful vaccination in infants whohad undergone unanesthetized circumcision in comparison toinfants who were uncircumcised or who received analgesiaduring circumcision (Gunnar et al, 1995; Taddio et al, 1995a;Taddio & Ohlsson, 1997). Findings from two studies suggestthat the pain experience in the neonatal intensive care unit(NICU) may alter the normal course of development of painexpression in toddlers and preschoolers (Grunau et al, 1994a,1994b). A recent study also suggests that prematurely bornchildren and adolescents had more tender points and lowertenderness thresholds than children born at full term (Buskilaet al, 2003). Animal research suggests that pain and stress inthe neonatal period result in altered pain sensitivity, decreasedweight gain, decreased ability to learn, and increasedpreference for alcohol (Anand & Plotsky, 1995). Humans and animals do not become tolerant to pain and are likelysensitized to the effects of pain over time. Thus recog-nition and treatment of pain is important for the immediatewell-being of infants and for their optimal long-termdevelopment.

CLINICAL ASSESSMENT OF PAINPresently, no easily administered, widely accepted, uniformtechnique exists for assessing pain in infants. A multidimen-sional pain assessment tool that includes measurements forboth physiologic and behavioral indicators of pain is preferablegiven the multifaceted nature of pain (Walden, 2001). Arecent systematic integrative review found 17 multidimen-sional neonatal pain assessment tools, but only 11 have beenpublished (Duhn & Medves, 2004). Since this systematicreview was published, at least one more multidimensional painassessment tool has been published (Cignacco et al, 2004).Selection of an appropriate clinical pain assessment methodshould be based first on the developmental age of the infant,and second on the type of pain experienced (e.g., forprocedural pain or postoperative pain). Validity, reliability,clinical utility, and feasibility are important aspects to considerwhen choosing a pain assessment tool.

Multidimensional Pain ToolsThe most commonly used published multidimensional infant-specific pain assessment tools with psychometric data are listedin Table 17-1. The CRIES (Krechel & Bildner, 1995) and thePain Assessment Tool (PAT; Hodgkinson et al, 1994) weredeveloped for postoperative pain and the Neonatal Infant PainScale (NIPS; Lawrence et al, 1993) and the Scale for Use inNewborns (SUN; Blauer & Gerstmann, 1998) were developedfor procedural pain. The Bernese Pain Scale for Neonates(BPSN; Cignacco et al, 2004) was specifically developed toassess the responses of preterm neonates or those who requiremechanical ventilation to procedural pain.

The infant pain assessment tool that has been most widelyvalidated in premature and full-term infants during proceduralpain is the Premature Infant Pain Profile (PIPP; Stevens et al,1996). The PIPP is a seven-indicator measure that includesbehavioral, physiologic, and contextual indicators. Gestationalage and behavioral state of the infant are taken intoconsideration in the scoring. This measure had initial validityand reliability determined by four retrospective data sets.Clinical validation that included the establishment of interraterand intrarater reliability was determined prospectively(Ballantyne et al, 1999). Clinical utility has been establishedby comparing the PIPP and the CRIES. The PIPP primarilyhas been used to evaluate procedural pain in preterm neonatesgreater than 28 weeks’ gestational age, but has also beenvalidated for evaluating postoperative pain in neonates and fordetermining the efficacy of pain-relieving interventions inpremature infants (Eriksson et al, 1999; Stevens et al, 1999).

Factors That Influence PainPain is unique among neurologic functions because of thedegree of plasticity in pain neurophysiology. Although structuraland functional maturity is reached at an early age, anatomicand functional changes occur throughout life and are related tothe effects of each pain experience. This plasticity means thatthe perception and meaning of pain are unique to each indi-vidual and are not determined by maturation alone but areinfluenced by many individual and contextual factors.Currently available methods to assess pain in infants do notadequately or quantitatively incorporate all aspects of thecontext of pain that influence the pain experience. Thus theclinician must remain cognizant of the ways in whichperception of pain may be positively or negatively influenced

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by these factors and subjectively incorporate them into theassessment of pain. These factors do not influence pain inisolation but are listed separately for clarity.

Biologic FactorsGenetic variation leads to differences in the amount and typeof neurotransmitters and receptors that are available tomediate pain. Recent advancements in molecular biology haveallowed for investigation of the genes responsible for painperception and modulation. Limited data suggest that gendermay also influence pain behaviors, with females expressingincreased behavioral responses to acute pain compared to malenewborns. It is unknown whether these gender differences arerelated to pain processing or pain expression (Fuller, 2002;Guinsburg et al, 2000).

Previous pain experience leads to alterations in pain signalprocessing that may be reversible or permanent. Studies ofpremature infants (Johnston & Stevens, 1996; Stevens et al,1999) suggest that previous pain experience is the mostimportant factor accounting for differences in response to theacute pain of heelstick. Infants who were subjected to morefrequent painful procedures in the NICU had decreasedbehavioral and increased cardiovascular responses compared toinfants who experienced less pain, even after controlling forgestational age–related differences in pain expression.

Behavioral StateThe behavioral state of the infant, ranging from deep sleep to awake and crying, acts as a moderator of behavioral painresponses. The behavioral state of the infant immediatelybefore the painful stimulus affects the robustness of theresponse. Infants in awake states demonstrate more robustreactions to pain than infants in sleep states. Infants in a deepsleep state will show less vigorous facial expression in responseto heelstick than infants who are alert or aroused before the heelstick (Grunau & Craig, 1987; Stevens et al, 1994).Term and healthy preterm newborns who were handled or

immobilized before heelstick exhibited greater physiologic andbehavioral reactivity, thus indicating that previous stress mayresult in greater instability in response to pain (Porter et al, 1998).

Gestational AgeGestational age affects infant pain responses, with youngerinfants displaying fewer and less vigorous behavioral responsesto pain (Gibbins & Stevens, 2003; Stevens et al, 1994, 1996,1999). In addition, preterm neonates may demonstrate uniquebehaviors in response to noxious stimuli. Holsti and colleagues(2004) used the Newborn Individualized Developmental Careand Assessment Program (NIDCAP, Children’s Hospital,Boston, MA) to examine responses of preterm neonates to aheelstick procedure and found that preterm neonates mayuniquely respond to acute pain by increased flexion andextension of arms and legs, finger splay, fisting, frowning, andhand on face behaviors.

Pain CharacteristicsPain characteristics such as the source or cause of the pain(acute injury, disease), location, and timing of pain influencethe perception and response to pain. Most research has focused on the responses to acute pain caused by single noxiousstimuli. However, pain commonly occurs over a prolongedperiod or is recurrent in nature. Because of the tremendousplasticity within pain processing systems, these factors willsignificantly affect the infant’s experience of pain.

ParentsNurses who care for the infant in pain must care for the infant’sfamily as well. Parents have many concerns and fears abouttheir infants’ pain and about the drugs used in the treatment ofpain (Gale et al, 2004; Franck et al, 2005). Parents may fearthe effects of pain on their children’s development. They mayalso fear that their infant may become “addicted” to theanalgesics (Franck et al, 2000). Nurses must be prepared torespond to questions from parents and encourage parent

Measure Age Level Indicators Pain Stimulus

CRIES Preterm and full-term Crying, requires oxygen for saturation >95%, Postoperative paininfants up to 60 weeks’ increased vital signs (heart rate and bloodgestational age pressure), expression, sleepless

Bernese Pain Scale Preterm and full-term Alertness, crying, time to calm, skin color, Procedural pain infor Neonates neonates eyebrow bulge with eye squeeze, posture, neonates with or(BPSN) breathing pattern, heart rate, oxygen saturation without ventilation

Neonatal Infant Pain Preterm and full-term Facial expression, cry, breathing patterns, arms, Procedural painScale (NIPS) neonates legs, state of arousal

Pain Assessment Full-term neonates Posture, tone, sleep pattern, expression, color, cry, Postoperative painTool (PAT) respirations, heart rate, oxygen saturation, blood

pressure, nurses’ perception of infant painPremature Infant Pain Preterm and full-term Gestational age, behavioral state, heart rate, Procedural and

Profile (PIPP) neonates oxygen saturation, brow bulge, eye squeeze, postoperative painnasolabial furrow

Scale for Use in Preterm and full-term Central nervous system state, breathing, Procedural painNewborns (SUN) infants movement, tone, face, heart rate, and

blood pressure,

Adapted from Franck LS et al (2000). Pain assessment in infants and children. Pediatric clinics of North America 47(3):487-512.

Multidimensional Pain Assessment Tools in InfantsTABLE 17-1

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participation in providing nonpharmacologic comfort measuresto their infants. Parents must be reassured that they are expectedto ask questions about their infants’ pain management.

Practitioner FactorsThe knowledge, attitudes, and beliefs of health care pro-fessionals have played a major factor in the undertreatment ofpain in both adults and children, despite emerging scientificevidence. Fear of addiction and disproportionate concern for side effects has resulted in severe underuse of opioidanalgesics for acute postoperative pain for infants and children(Sredl, 2003).

Lack of education about pain in nursing and medicaleducation is a major cause of myths and biases that impedeappropriate assessment and management of pain in infants.Research has shown that infant pain management is stronglyinfluenced by a nurse’s biases, personal experiences with pain,and area of specialization. Nurses must examine closely theirown beliefs and attitudes about pain, explore the impact thattheir attitudes might have on their patient care, and challengetheir beliefs to determine whether they are science-based ortradition-based. Hester (1998) describes an “illusion ofcertainty” in which providers assume they know the level of apatient’s pain without having to measure it based on the illnessor procedure, without regard to the individual patient’sexperience. Use of validated pain assessment tools results ingreater consistency in provider ratings of pain and may moreaccurately reflect pain experienced by preverbal infants.

MANAGEMENT OF NEONATAL PAINThe goals of pain management in infants are (1) to minimizeintensity, duration, and physiologic cost of the painexperience; and (2) to maximize the infant’s ability to copewith and recover from the painful experience. Depending onduration and severity, pain may be successfully managed withnonpharmacologic and/or pharmacologic therapies.

Nonpharmacologic ManagementPainful procedures in the NICU are unavoidable; therefore itis vital that caregivers assist infants to cope with and recoverfrom necessary but painful clinical procedures. Nonpharmacologicstrategies can reduce neonatal pain indirectly by reducing thetotal number of noxious stimuli to which infants are exposed.Strategies to prevent pain should be employed wheneverpossible, including grouping blood draws to minimize thenumber of venipunctures per day, establishing central vesselaccess to minimize vein and artery punctures, and limitingadhesive tape and gentle removal of tape to minimizeepidermal stripping.

Nonpharmacologic strategies are hypothesized to directlyreduce pain by (1) blocking nociceptive transduction or trans-mission; (2) activating descending inhibitory pathways; or, (3)activating attention or arousal systems that modulate pain.Nonpharmacologic strategies such as hand or blanketswaddling, nonnutritive sucking, and oral sucrose may helpminimize neonatal pain and stress while maximizing theinfant’s own regulatory and coping abilities.

SwaddlingSeveral positioning and containment strategies have beeninvestigated as nonpharmacologic strategies to minimize painin the neonatal population. Although prone positioning of

neonates has been demonstrated to promote sleep and improverespiratory function, it has not been found to be helpful inminimizing minor procedural pain in preterm neonates(Grunau et al, 2004; Stevens et al, 1999). Containmentstrategies to limit excessive, immature motor responses have,however, been demonstrated to be effective in minimizing painresponses in preterm neonates.

Swaddling is thought to reduce pain by providing gentlestimulation across the proprioceptive, thermal, and tactilesensory systems. Several studies have been conducted in thepreterm population using different methods of swaddling. Ahand swaddling technique known as “facilitated tucking”(holding the infant’s extremities flexed and contained close tothe trunk), has been shown to reduce pain responses in pretermneonates. In a study by Corff et al (1995), preterm infantsundergoing a heelstick procedure demonstrated significantlyreduced heart rates and crying, and more stability in sleep-wake cycles, in the hand-swaddled position. Hand-swaddlingwas also demonstrated to be effective in reducing proceduralpain of endotracheal suctioning (Ward-Larson et al, 2004).

A similar containment study conducted by Fearon et al(1997) used blanket swaddling for nesting. The researchersexamined the effectiveness of blanket swaddling after a heellance in younger (<31 weeks’ postmenstrual age) and older (ator older than 31 weeks’ postmenstrual age) preterm infants.Trends showed that blanket swaddling was effective forreducing heart rate and negative facial displays in the post-heelstick phase for the older infants and increased oxygensaturation levels in younger infants.

Nonnutritive Sucking (NNS)NNS is the provision of a pacifier into the mouth to promotesucking without the provision of breast milk or formula fornutrition. Franck (1987) found that pacifiers were ranked byNICU as the first choice of pain intervention. NNS is thoughtto produce analgesia through stimulation of orotactile andmechanoreceptors when a pacifier is introduced into theinfant’s mouth. NNS is hypothesized to modulate transmissionor processing of nociception through mediation by theendogenous nonopioid system (Blass et al, 1987; Gunnar et al,1988).

NNS has been shown to reduce behavioral pain responsesin term infants during immunizations (Blass, 1997) and heellances in term and preterm infants (Blass & Shide, 1994; Field& Goldson, 1984; Miller & Anderson, 1993). One study foundthat NNS reduced composite pain responses in preterm infantsduring heel lances (Stevens et al, 1999). However, pain reliefwas greater in infants who received both NNS and sucrose.Compared to blanket swaddling (Campos, 1989) or rocking(Campos, 1994) during painful procedures, NNS reducedduration of cry and soothed infants more rapidly. Unlike withblanket swaddling, however, a rebound in distress occurredwhen the NNS pacifier was removed from the infants’ mouths.Therefore the efficacy of NNS is immediate but appears toterminate almost immediately on cessation of sucking.

SucroseSucrose with and without NNS has been the most widelystudied nonpharmacologic intervention for infant painmanagement. Sucrose is a disaccharide that comprises fructoseand glucose. A systematic review of 21 randomized controltrials of full-term and preterm infants (N = 1616) on the

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efficacy of sucrose for relieving pain found that sucrosedecreased crying time, heart rate, facial action, and compositepain scores during heel lance and venipuncture (Stevens et al,2004). A pain reduction response is noted with dose volumesranging from 0.05 ml to 2 ml of a 24% solution administeredapproximately 2 minutes before the painful stimulus (Stevenset al, 1997). This 2-minute time interval appears to coincidewith endogenous opioid release triggered by the sweet taste ofsucrose (Stevens et al, 1999). The use of sucrose in com-bination with other behavioral interventions such as pacifiers,rocking, holding, and skin-to-skin holding may enhance theanalgesic effect of sucrose (Stevens et al, 2004).

Two randomized controlled trials evaluated sucrose forimmunizations. Two milliliters of 50% to 75% sucrose waseffective for immunization pain in infants from 2 to 6 monthsof age (Lewindon et al, 1998; Ramenghi et al, 2002).

Although relatively few contraindications to the provisionof swaddling and nonnutritive sucking for management of painin neonates exist, the absolute safety of sucrose has not beendetermined. Rare instances of choking and decreased oxygensaturation, all resolving spontaneously, have been reported(Gibbins & Stevens, 2003; Stevens et al, 2004). Sucroseshould be used with caution in extremely preterm neonates,critically ill newborns, neonates with unstable blood glucoselevels, and infants at risk for necrotizing enterocolitis.Furthermore, sufficient evidence of the safety of repeated dosesof sucrose in neonates to recommend its widespread use forrepeated painful procedures is lacking (Stevens et al, 2004;Walden, 2001).

In general, nurses should begin with nonpharmacologicinterventions before progressing to pharmacologic agents.However, nonpharmacologic interventions may not beappropriate for situations involving severe or prolonged pain.

Pharmacologic ManagementPharmacologic agents are often required to alleviate moderateto severe procedural, postoperative, or disease-related pain inneonates. Systemic analgesia, epidural anesthesia and analgesia,topical anesthetics, nonopioid analgesia, and adjunctivemedications are reviewed.

OpioidsOpioid analgesics are considered the gold standard for painrelief. The most commonly used drugs for analgesia andsedation in neonates are listed in Table 17-2.

Opioids are often the preferred choice to manage moderateto severe pain in neonates. Advantages of opioid therapyinclude (1) prolonged clinical experience with their use inpreterm and full-term neonates; (2) analgesic potency withouta ceiling effect; (3) ability to produce sedation in ventilatedpatients; (4) few hemodynamic side effects; and (5) availabilityof antagonist drugs such as naloxone to reverse adverse sideeffects (Anand et al, 2000).

Morphine. Morphine is the most widely studied opioidanalgesic in critically ill and postoperative neonates. Meanelimination half-life following single-dose administration ofmorphine ranges between 2.6 and 14 hours (Bhat et al, 1990,1994). Differences exist in the pharmacokinetics of morphineadministered to premature neonates in the first week of life(Bhat et al, 1990). After bolus administration, neonates of less than 40 weeks’ gestation have longer elimination half-lives and delayed clearance of morphine than olderneonates. In addition, plasma proteins in premature neonatesunbind approximately 80% of morphine. This unboundmorphine may account for its increased central nervous systemconcentrations. When morphine was administered as acontinuous infusion, plasma concentrations were three

364 UNIT II SPECIAL CONSIDERATIONS

Drug Intermittent Doses Infusion Dose

Opioid AnalgesicsMorphine 0.05 to 0.1 mg/kg/dose IV repeated every Loading Dose: 0.1 mg/kg/dose IV infused over 11/2 hours

4 hours as needed Maintenance Dose: 0.015 to 0.020 mg/kg/hr IVFentanyl 1 to 4 mcg/kg/dose IV repeated every Loading Dose: 1 mcg/kg IV

2 to 4 hours as needed Maintenance Dose: 0.5 mcg/kg/hr up to 4 mcg/kg/hr IVMethadone 0.05 to 0.2 mg/kg/dose IV repeated

every 6 to 12 hours as needed

Nonsteroidal Anti-inflammatory DrugsAcetaminophen 10 to 15 mg/kg/dose PO repeated every

6 to 8 hours as needed20 to 25 mg/kg/dose PR repeated every

6 to 8 hours as needed

BenzodiazepinesMidazolam 0.05 to 0.1 mg/kg/dose IV every 2 to Loading Dose: 0.05 to 0.2 mg/kg IV

4 hours prn Maintenance Dose: 0.2 mcg/kg/min up to0.6 mcg/kg/min

Miscellaneous AgentsChloral Hydrate Intermittent Dose: 20 to 40 mg/kg/dose

every 4 to 6 hours as needed PO/PRSingle Dose: 30 to 75 mg/kg/dose PO/PR

Adapted from Zenk KE et al (2003). Neonatal medications & nutrition: a comprehensive guide, ed 3. Santa Rosa, CA: NICU Ink.

Commonly Used Drugs for Analgesia and Sedation in NeonatesTABLE 17-2

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times greater, and the elimination half-life was seven times longer, in neonates than in older infants and children.

Effective concentrations of morphine for analgesia andsedation are inconclusive and dependent on the age of thepatient, hepatic function, renal function, and clinicalcondition (Dagan et al, 1993; Faura et al, 1998; Scott et al,1999). A study by Bouwmeester et al (2003) found thatpostoperative neonates have a narrower therapeutic windowfor morphine analgesia than older infants and toddlers.

The effectiveness of morphine for acute pain caused byinvasive procedures remains unclear. Although earlier studiessupported the effectiveness of morphine analgesia for acutepain (Anand et al, 1999; McCulloch et al, 1995; Scott et al,1999), more recent studies refute its effectiveness (Anand etal, 2005). No analgesic efficacy of intravenously administeredmorphine was noted on postoperative pain, endotracheal tubesuctioning, or heel lances (Carbajal et al, 2005; Franck et al,2000; Simons et al, 2003b).

Morphine has few effects on the neonatal cardiovascularsystem in the well hydrated neonate. Hypotension, bradycardia,and flushing are part of the histamine response to morphineand can be decreased by slow intravenous bolus administration(over 10 to 20 minutes) and optimizing intravascular fluidvolume (Anand et al, 2000; Stoelting, 1995). As morphinepredisposes patients to hypotension, a recent study by Hall et al (2005) recommends that morphine administration inpreterm neonates between 23 and 26 weeks with preexistinghypotension be used with caution, as morphine has been foundto be associated with adverse neurologic outcomes includingsevere intraventricular hemorrhage (IVH) and death. Althoughrelatively uncommon, the effects of histamine release may alsocause bronchospasm in infants with chronic lung disease(Anand et al, 2000). Enterohepatic recirculation of morphinemay contribute to rebound increases in plasma levels and laterespiratory depression (Bhat et al, 1990, 1992). Decreasedintestinal motility and abdominal distention may also occurcausing a delay in the establishment of enteral feeding inpreterm neonates (Saarenmaa et al, 1999). The effect ofmorphine on gastrointestinal motility is hypothesized to bedose-dependent, and tolerance of enteral feeds may beimproved by priming the gut with small volumes of milk andlower doses of morphine (Anand et al, 2000).

Despite relatively few side effects, full-term and especiallypreterm neonates remain susceptible to morphine toxicity thatresults from gradually increasing plasma concentrations. Closemonitoring and individual titration of the amount andfrequency of doses for all neonates receiving morphine therapyis therefore important (Anand et al, 2000).

Fentanyl. Randomized clinical trials in neonates havefound that fentanyl is approximately 13 to 20 times morepotent than morphine (Saarenmaa et al, 1999). Fentanyl isprobably the most widely used analgesic in neonates and offerstwo distinct advantages over morphine (Anand et al, 2000).First, fentanyl causes less histamine release than morphine andmay be more appropriate for infants with hypovolemia orhemodynamic instability, congenital heart disease, or ex-preterm infants with chronic lung disease (Anand et al, 2000).Second, fentanyl blunts increases in pulmonary vascularresistance. This finding makes it potentially useful in managingpain in neonates with persistent pulmonary hypertension, inneonates during extracorporeal membrane oxygenation, and in neonates after cardiac surgery (Anand et al, 2000).

Fentanyl has a more rapid onset and shorter duration ofaction compared with morphine and must be administered as a continuous infusion or as an intravenous bolus every 1 to 2 hours. Fentanyl is a highly lipophilic compound that crossesthe blood-brain barrier more rapidly and has a longerelimination half-life than morphine (6 to 32 hours after asingle-dose administration of fentanyl) (Anand et al, 2000).Accumulation of fentanyl in fatty tissues with extended use mayprolong its sedative and respiratory depressant effects and may beresponsible for the rebound increase in plasma levels observedfollowing discontinuation of therapy in neonates (Anand et al,2000). The liver metabolizes more than 90% of fentanyl.

Rarely, fentanyl can significantly reduce chest wallcompliance (stiff chest syndrome). This naloxone-reversibleside effect can be prevented by slow infusion (as opposed torapid bolus administration), administration of doses less than3 mcg/kg, or concomitant use of muscle relaxants.

The administration of fentanyl is associated with a modestincrease in intracranial pressure (Anand et al, 2000). Cautionis therefore recommended for administration of fentanyl topatients with intracranial pathology.

Increased intra-abdominal pressure can triple the elimi-nation half-life of fentanyl, probably because of reducedhepatic artery blood flow. Although it has only beendemonstrated for fentanyl, increased intra-abdominal pressureprobably occurs with other opioids that are metabolized by theliver. Because many neonates experience increased intra-abdominal pressure, elimination is an important considerationin administering opioids to neonates.

Prevention of Opioid Withdrawal Symptoms.Neonates who require opioid therapy for an extended period oftime may develop physical dependence and withdrawal. Rapidweaning of opioids may lead to withdrawal symptoms such asirritability, crying, increased respiratory rate, jitteriness, hyper-tonicity, vomiting, diarrhea, sweating, skin abrasions, seizures,yawning, stuffy nose, sneezing, and hiccups. The prevalence ofopioid withdrawal is greater in infants after continuousinfusions of fentanyl than continuous infusions of morphine(Franck et al, 1998). Dominguez et al (2003) reported a 53%incidence in opioid withdrawal in neonates who received aminimum of 24 hours of fentanyl by continuous infusion. Inthis study, the most significant risk factors for opioid with-drawal were higher total dose and longer infusion duration. Inall neonates with withdrawal, onset of withdrawal symptomsoccurred within 24 hours of discontinuation of the fentanylinfusion. Data are insufficient to determine the optimalweaning rate of opioids to prevent withdrawal symptoms inneonates on opioid therapy. Ducharme et al (2005) reportedthat adverse withdrawal symptoms in children who receivedcontinuous infusions of opioids and/or benzodiazepines couldbe prevented when the daily rate of weaning did not exceed20% for children who received opioids/benzodiazepines for 1 to 3 days; 13% to 20% for 4 to 7 days; 8% to 13% for 8 to 14 days; 8% for 15 to 21 days; and 2% to 4% for more than 21 days, respectively. Abstinence scoring methods commonlyused in the care of the infant with prenatal drug exposure mustbe used in assessing the infant during opioid weaning (Franck& Vilardi, 1995).

Methadone. Methadone is a synthetic opioid thatproduces prolonged analgesia and has good oral bioavailability,thus making it an attractive option to treat postoperative pain in neonates (Berde et al, 1991) and prevent neonatal

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abstinence syndrome (Maas et al, 1990). When an infant isbeing weaned from opioid therapy to a longer-acting oralmedication such as methadone, the starting dose of methadoneshould be calculated to provide a dose equivalent to the doseof opioid the neonate is receiving (American Academy ofPediatrics et al, 2000). Further weaning should then beaccomplished based on frequent reassessment to ensure thatthe patient is free of pain and withdrawal symptoms. Studiesare needed to further establish the pharmacokinetics anddosing requirements of methadone in neonates.

Epidural Anesthesia and AnalgesiaEpidural anesthesia and analgesia is a relatively new optionavailable to manage surgical and postoperative pain in manyNICUs. Morphine or fentanyl administered alone or in com-bination with local anesthetics into the epidural space canprovide good intraoperative anesthesia and postoperativeanalgesia after abdominal or lower extremity surgery(Ochsenreither, 1997). Epidural analgesia should not be usedin patients with sepsis or local infection at the insertion site,thrombocytopenia or other known coagulopathy, increasedintracranial pressure, suspected neurologic disease, or mal-formations of the vertebral column. It also should not be used in infants who cannot tolerate a decrease in systemicvascular resistance such as those with tetralogy of Fallot(Ochsenreither, 1997).

Use of epidural analgesia may potentially expediteextubation (Murrell et al, 1993; Sethna & Koh, 2000; Valley& Bailey, 1991). Because opioids added to local anestheticinfusions act directly on the neurons in the spinal cord, lowerdoses of local anesthetic are required for epidural admin-istration, and fewer opioid-related side effects are generallyseen. Opioid-related side effects can still occur and requirecareful monitoring of the patient for side effects such asrespiratory depression or urinary retention. Catheter-relatedside effects include catheter migration, infection, occlusion,neural injury/paresthesia, catheter breakage on removal, orhematoma formation at the site of insertion (Ochsenreither,1997). Anesthetic-related side effects include injection intothe cerebrospinal fluid that results in a high block with muscleparalysis or injection into a blood vessel resulting in seizures,hypotension, dysrhythmia, or cardiac arrest (Ochsenreither,1997).

Epidural anesthesia and analgesia requires specially trainedhealth care personnel and involves appropriate and closeobservation (American Academy of Pediatrics et al, 2000). Inaddition to monitoring for opioid-related, catheter-related,and anesthetic-related side effects, nursing care of neonateswho are receiving epidural analgesia includes regular inspec-tion of the catheter site for leakage, drainage, hematoma, anderythema. The infusate, dose, and rate of the infusion shouldbe carefully checked, and the area should be kept clean and dry(Ochsenreither, 1997).

Topical Application of Local AnestheticsEMLA Cream. EMLA cream (eutectic mixture of local

anesthetics, lidocaine, and prilocaine; Astra Pharmaceuticals,London) is approved for use in infants at birth with agestational age of 37 weeks or greater for a variety of clinicalprocedures. EMLA produces topical anesthesia when appliedas a cream to the surface of intact skin and then covered withan occlusive dressing (Stoelting, 1995). The primary concern

with the use of EMLA is methemoglobinemia caused byprilocaine toxicity (Sethna & Koh, 2000). Neonates, par-ticularly preterm neonates, are at increased risk because of athinner stratum corneum and less active NADH-dependentmethemoglobin reductase enzymes that result in higher plasmalevels (Sethna & Koh, 2000). Neonates with anemia, sepsis,hypoxemia, or metabolic acidosis and who are receiving othermethemoglobin-inducing drugs such as acetaminophen,phenytoin, phenobarbital, or nitroprusside may also be atincreased risk for development of systemic toxicity (Sethna &Koh, 2000). Although it is not routinely recommended for use inpreterm neonates, one study found that a single dose of 0.5 gEMLA cream applied for 60 minutes to the intact skin of preterminfants older than 30 weeks’ gestation did not result in significantincreases in blood methemoglobin concentrations (Taddio et al,1995b). In addition to the risk of methemoglobinemia, local skinreactions have been noted with EMLA cream and have includedblanching, redness, and transient purpuric lesions (Sethna &Koh, 2000). Policies and procedures regarding application ofEMLA cream should be established to maximize pain reliefwhile minimizing the potential side effects.

Three primary factors determine the effectiveness of EMLAcream: dose, size of application area, and duration of exposure(Sethna & Koh, 2000). The recommended dose in neonates is0.5 to 2 g applied to the procedure site 1 hour before theprocedure and covered with an occlusive dressing (Anand &International Evidence-Based Group for Neonatal Pain,2001). Multiple studies document the efficacy of EMLA inreducing pain associated with venipunctures and circumcisions(Anand et al, 2005). EMLA has also been documented to beeffective in managing pain associated with lumbar puncture(Kaur et al, 2003). EMLA has not been shown, however, to beeffective in managing pain associated with the heelstickprocedure (Anand et al, 2005).

Tetracaine 4% Gel. Tetracaine 4% gel (Ametop; Smith& Nephew, London) has also been investigated in neonates for management of procedural pain. Tetracaine gel has beenfound to be effective in managing pain associated withvenipunctures and intravenous cannulation (Jain & Rutter,2000; Moore, 2001), but ineffective for heel sticks andpercutaneous inserted central catheter (PICC) insertions (Jainet al, 2001; Ballantyne et al, 2003).

LMX 4%. Another topical local anesthetic currently usedin pediatrics for management of procedural pain is liposomallidocaine cream (LMX 4%; Ferndale Laboratories, Michigan).Several studies have evaluated the efficacy of LMX and EMLAand found a 30-minute application of LMX to be as effective as a 60-minute application of EMLA for producing topicalanesthesia for peripheral intravenous access in older children(Eichenfield et al, 2005; Kleiber et al, 2002; Koh et al, 2004).Similar results were found in a recent study in neonates thatfound LMX to be equally effective as EMLA in reducing thepain of circumcision in term newborns (Lehr et al, 2005).LMX may offer an improved risk-benefit profile compared toEMLA considering the faster onset of action and no risk ofmethemoglobinemia. Further studies in neonates are needed toestablish the safety and efficacy of LMX for management ofprocedural pain in neonates.

Nonopioid AnalgesicsAcetaminophen. Acetaminophen is a nonopioid analgesic

for short-term management of mild to moderate pain in

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neonates. Acetaminophen has been commonly administeredin neonates as an oral or rectal preparation. When aceta-minophen is administered concurrently with opioid analgesia,the effect is additive and allows a reduction in dosages of both drugs, resulting in fewer adverse side effects (Menon et al, 1998).

Little information is available on the pharmacokinetics of acetaminophen administration in neonates, especiallyadministration by the rectal route. However, studies in adultshave demonstrated greater than 80% bioavailability for orallyadministered acetaminophen (Depre et al, 1992). In children,peak concentrations of analgesic effect are reached in 30 to 60 minutes. The elimination half-life in newborns is estimatedto be less than or equal to 4.9 hours. Acetaminophen ismetabolized almost entirely by hepatic conjugation that isthen renally eliminated.

Although acetaminophen has been demonstrated tosignificantly reduce pain responses during skin excision andcomfort scores at 6 hours following the circumcision procedure(Howard et al, 1994), other studies have failed to demonstrateefficacy resulting from acute tissue injury of heelstick andpostoperative pain relief after cardiac surgery (Shah et al,1998; Van Lingen et al, 1999). The results from these studiessuggest that acetaminophen may be more appropriate for mildto moderate dull, continuous pain resulting from inflammatoryconditions than for acute, tissue-damaging, or severe noxiousstimuli (Anand et al, 2000).

At therapeutic doses, acetaminophen is well tolerated andhas a low toxicity (Olkkola & Hamunen, 2000). Becauseacetaminophen does not inhibit prostaglandin synthesis intissues other than the brain, common side effects ofnonsteroidal anti-inflammatory drugs—such as inhibition ofplatelet function, renal insufficiency, and gastrointestinalirritation—do not occur (Anand et al, 2000). The primaryconcern of acetaminophen is liver damage, but this should notbe a concern in neonates if standard doses are used (Berde etal, 1991).

Use of Adjunctive DrugsIn the NICU, the use of sedatives, alone or in combinationwith analgesics, is controversial. Although sedatives suppressthe behavioral expression of pain, they have no analgesiceffects and can even increase pain. Sedatives should only be used when pain has been ruled out. When administeredwith opioids, sedatives may allow more optimal weaning ofopioids in critically ill, ventilator-dependent neonates whohave developed tolerance from prolonged opioid therapy. Noresearch has been done to determine the safety or efficacy of combining sedatives and analgesics for the treatment of painin infants.

The most commonly administered sedatives in the NICUare benzodiazepines and chloral hydrate.

BenzodiazepinesMidazolam. Midazolam is a short-acting benzodiazepine

that has increasingly been used in the NICU to providesedation for mechanically ventilated neonates. Midazolam ispreferred over other benzodiazepines because of its watersolubility, rapid clearance, and shorter elimination half-life(6.5 hours) (Jacqz-Aigrain et al, 1992). Recent concern aboutthe safety of midazolam in neonates has been reported becauseof the large number of adverse neurologic effects associatedwith midazolam in term and preterm neonates (Adams et al,

1997; Magny et al, 1994; Ng et al, 2000). Transient neurologiceffects after boluses and/or infusions of midazolam includeimpaired level of consciousness, lack of visual following, hyper-tonia, hypotonia, choreic movements, dyskinetic movements,myoclonus, epileptiform activity, abnormalities in electroen-cephalograms, and cerebral hypoperfusion (Ng et al, 2000). Astudy by Anand et al (1999) also found a higher incidence of poor neurologic outcome as defined by death, severeintraventricular hemorrhage, and periventricular leukomalaciain ventilated preterm neonates treated with midazolam.

Diazepam. Diazepam is not recommended for adminis-tration in neonates because of its very prolonged half-life (20 to 50 hours), its long-acting metabolites, and concernabout the benzyl alcohol content. The dose of benzyl alcoholpreservative in diazepam is, however, below the dose known to cause fatal toxicity in premature neonates (100 to400 mg/kg/day). Diazepam displaces bilirubin from albumin-binding sites, thereby increasing the neonate’s risk of ker-nicterus (Anand et al, 2000).

Chloral Hydrate. Chloral hydrate has been used in singledoses to sedate neonates during pulmonary function,radiographic, and other diagnostic testing for which thepatient must lie still. The onset of action is approximately 30 minutes and the lasts about 2 to 4 hours, depending on thedose (Anand et al, 2000). Although clinically effective,concern has been raised about the potential carcinogenic andgenotoxic effects of chloral hydrate administered to animals.Chloral hydrate has also been used in repeated doses to sedateneonates on mechanical ventilation. Alternative sedatives(i.e., benzodiazepines) should be used when possible becausechloral hydrate has other gastrointestinal side effects and maybe associated with direct hyperbilirubinemia. The extremelylong half-life (greater than 72 hours) of chloral hydrateincreases the risk of toxicity with repeated administration,which may be manifest as increased agitation.

Management of Specific Pain TypesPain management techniques may vary based on pain type and clinical situation. This section will review special issuesrelated to procedural pain, postoperative pain, preemptiveanalgesia for mechanical ventilation, and pain management atend of life.

Procedural Pain. It has been estimated that newborninfants, particularly those born preterm, are routinelysubjected to an average of 61 invasive procedures performedfrom admission to discharge, with some of the youngest orsickest infants experiencing more than 450 painful proceduresduring their hospital stays (Barker & Rutter, 1995). Many of the procedures commonly performed in the neonate causemoderate to severe pain, with average pain scores of 5 on a 10-point scale (Simons et al, 2003a). Substantial numbers offailed attempts at procedures dramatically increase the numberof painful procedures that neonates are subjected to. Simons et al (2003a) found that the percentages of failed proceduresfor insertion of central venous catheters, insertion ofperipheral arterial catheters, and intravenous cannula inser-tion were 45.6%, 37.5%, and 30.9%, respectively. Thesefrequent, invasive, and noxious procedures occur randomly inthe NICU and many times are not routinely managed witheither pharmacologic or nonpharmacologic interventions(Simons et al, 2003a). Anand and the International Evidence-Based Group for Neonatal Pain (2001) provide guidelines for

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preventing and treating neonatal procedural pain. Strategiesfor the management of diagnostic, therapeutic, and surgicalprocedures commonly performed in the NICU are summarizedin Table 17-3.

Local anesthesia may not be sufficient for procedures thataffect deeper tissue, such as chest tube insertion or surgicalcutdown of vessels. Central analgesia is then required toprevent pain. For the nonventilated patient, in whom concernfor the respiratory depressant effects of opioids exists, one halfthe standard dose may be administered. The infant’s respi-ratory status and responsiveness to pain stimuli can then be

assessed before further drug administration. For the infant whois receiving opioid analgesics on a regular basis, a controlledinfusion of a bolus dose may be required to provide adequateanalgesia during an invasive procedure.

Postoperative Pain. Adequate analgesia is importantduring the immediate postoperative period for the optimalrecovery of the patient. Unrelieved pain can interfere withventilation and delay weaning. In general, it is thought thatthe use of low-dose continuous infusions of opioid analgesicsprovide more constant, effective pain relief with less med-ication than intermittent scheduled doses of opioids (Truog &

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Swaddling,Pacifier Containment, Subcutaneouswith or Facilitated EMLA Infiltration of

Procedures Sucrose Tucking Cream Lidocaine Opioids Other

Diagnostic ProceduresArterial puncture √ √ √ √Heel lancing √ √ Consider venipuncture; skin-

to-skin contact with mother;mechanical spring-loaded lance

Lumbar puncture √ √ √ Use careful physical handlingVenipuncture √ √ √Eye examination √ √ Consider topical anesthetic

Therapeutic ProceduresCentral venous line √ √ √ √ √ Consider general anesthesia

placementChest tube insertion √ √ √ Anticipate need for intubation and

ventilation in neonatesspontaneously breathing;consider short-acting anestheticagents; avoid midazolam

Gavage tube insertion √ √ Gentle technique and appropriatelubrication lubrication

Intramuscular injection √ √ √ Give drugs intravenously, wheneverit is possible

Peripherally inserted √ √ √ √central catheter placement

Endotracheal intubation √ Various combinations of atropine,ketamine, thiopental sodium,succinylcholine chloride,morphine, fentanyl,nondepolarizing musclerelaxant; consider topicallidocaine

Endotracheal suction Sucrose √ √ Sprayoptional

Surgical ProceduresCircumcision √ √ Mogen clamp preferred over

Gomco clamp; dorsal penilenerve block, ring block, or caudalblock using plain or bufferedlidocaine; consideracetaminophen forpostoperative pain

Adapted from Anand KJ, the International Evidence-Based Group for Neonatal Pain (2001). Consensus statement for the prevention and managementof pain in the newborn. Archives of pediatric adolescent medicine 155:173-180.

Suggested Management of Painful Procedures Commonly Performed in the NICUTABLE 17-3

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Anand, 1989). However, a more recent study by Bouwmeesteret al (2003) found no difference in the safety or effectivenessof intermittent doses of morphine compared with continuousinfusions of morphine.

Preemptive Analgesia for Mechanical Ventilation.Opioids are frequently used to sedate, promote respiratorysynchrony, produce physiologic stability, and relieve pain ordiscomfort in ventilated neonates (Anand et al, 1999). Arecent Cochrane database systematic review, however,concludes that there is insufficient evidence available torecommend the routine use of opioids in mechanicallyventilated neonates (Bellu et al, 2005).

In a multicenter trial of 898 ventilated preterm infantsbetween 23 and 32 weeks’ gestation, Anand et al (2004) foundthat preemptive analgesia using morphine decreased clinicalsigns of pain but did not reduce the frequency of severe IVH,periventricular leukomalacia, or death in ventilated neonates.This study did, however, demonstrate that additionalintermittent boluses of morphine were associated withincreased rate of adverse neurologic outcomes.

Several secondary analyses of this data have been publishedexamining hypotension and short-term pulmonary outcomes.Hall et al (2005) found that pre-emptive morphine infusions,additional bolus morphine doses, and lower gestational agewere associated with hypotension among preterm neonates.The researchers report that this pre-existing hypotension wasassociated with the findings of severe IVH and death, butmorphine therapy did not contribute to these outcomes.Bhandari et al (2005) demonstrated that infants in themorphine group required significantly longer ventilatorytherapy compared to the placebo group and that additionaldoses of morphine were associated with increased air leaks andlonger durations of high-frequency ventilation, nasalcontinuous airway pressure, and oxygen therapy.

Pain Management at End-of-Life (EOL). Pain manage-ment at end- of-life (EOL) primarily centers on the provisionof opioids to minimize pain and nonpharmacologic therapiesto enhance the infant’s comfort level (Walden et al, 2001).Pain assessment is extremely difficult in neonates at end of life.Therefore caregivers must often consider risk factors for painand rely on physiologic measures such as increases in heart rateand decreases in oxygen saturation to make pain managementdecisions.

Continuous infusions of opioid therapy such as morphineand fentanyl are often required to manage pain at EOL andshould be titrated to desired clinical response (analgesia)(Anand et al, 2000). Opioid doses well beyond those describedfor standard analgesia are often required for infants who are insevere pain or who have developed tolerance (decreasing painrelief with the same dosage over time) after the prolonged useof opioids (Partridge & Wall, 1997).

Physiologic comfort measures may palliate pain anddistressing symptoms in infants at EOL and include reductionof noxious stimuli, organization of caregiving, and positioningand containment strategies (Walden et al, 2001).

NEONATAL NURSE’S ROLE ANDRESPONSIBILITIESProvision of comfort and relief of pain are two primary goals of nursing care. To accomplish these goals, neonatal nursesmust (1) prevent pain when possible; (2) assess pain in theirneonatal patients who cannot verbalize their subjective

experience of pain; (3) provide relief or reduction of painthrough implementation of nonpharmacologic and/or pharma-cologic measures; and (4) assist the infant in coping when paincannot be prevented.

The effective management of infant pain requires nursesto collaborate with each other, with physicians, and with theinfant’s parents. Nurses must effectively communicate assess-ments and recommendations in an objective, concise mannerand advocate for pain relief strategies with responsible healthcare team members.

Neonatal nurses must remain informed about professionalstandards and clinical guidelines related to pain assessmentand management in neonates. The nurse should also participatein ongoing pain education and review of new research andscientific developments.

SU M MARYPain in neonates is often assessed and managed inadequately ina large proportion of neonates in the NICU. It is clear,however, that caring for infants in pain requires attention notonly to the immediate effects but also to the long-termdevelopmental consequences of pain and pain treatment.Through ongoing research, objective assessment, effectivecollaboration, and systematic application of treatment plans,nurses will achieve greater comfort for individual patients andadd to the body of knowledge in this rapidly evolving field.

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