CHAPTER 16 1. Review the physiology of acute pain in preterm neonates. 2. Discuss current standards for assessing and managing pain in neonates. 3. Identify behavioral and physiologic responses that are indicative of pain in the neonate. 4. Select a valid and reliable composite measure for assessment of pain in neonates. 5. Discuss the evidence base for nonpharmacologic and pharmacologic approaches to the management of pain in neonates. Advances in neonatal care during the past several decades have led to the increased survival of extremely preterm and sick neonates who regularly are subjected to numerous diagnostic and therapeutic procedures that are painful but medically necessary to their care. The prevention of pain in these critically ill neonates not only is an ethical obligation but may also minimize the immediate and cumulative effects of repeated painful experiences on the developing brains of these vulnerable neonates. Despite impressive gains in the knowledge related to the assessment and management of pain in neonates over the last several decades, a large gap still exists between routine clinical practice and scientific evidence. This chapter will review pain pathways, identification of pain, and interventions to alleviate pain in the neonate. The International Association for the Study of Pain (IASP) defines pain as “unpleasant sensory and emotional experience associated with actual or potential tissue damage, or described in terms of such damage” (IASP Subcommittee on Taxonomy, 1979, p. 250). The IASP definition implies that the meaning of pain must be learned through experience and articulated within the context of verbal language. This conceptualization of pain perpetuates the misconception that infants, who lack linguistic skills, do not experience pain (Anand and Craig, 1996). In neonates, physiologic, behavioral, and hormonal indicators provide objective and quantifiable information about the location, intensity, and duration of painful stimuli. These responses can be used in conjunction with other contextual indicators to infer the existence of pain. A. Many activities and interventions in the neonatal intensive care unit (NICU) cause pain. The most frequently occurring painful procedures include nasal and endotracheal suctioning, heel stick, adhesive removal, and venous and arterial punctures (Carbajal et al., 2008). B. Frequency of invasive procedures is inversely related to gestational age and severity of illness. Therefore, the smaller and sicker neonates are those subject to the greatest numbers of most painful procedures. 1. Carbajal and colleagues (2008) found that infants born between 24 and 42 weeks of gestation experienced on average a mean of 98 painful procedures during the first 14 days of admission, with one neonate having 364 painful procedures. C. The number of procedures encountered by infants in the NICU is partially due to a substantial number of failed attempts. 1. In the study by Simons and colleagues (2003), the failure rates for placement of central venous catheters, peripheral arterial catheters, and intravenous (IV) cannulas were 45.6%, 37.5%, and 30.9%, respectively. 2. In the study by Carbajal et al. (2008), some of the most painful procedures needed as many as 10 to 15 attempts for completion. D. Despite safe, effective pharmacologic and nonpharmacologic interventions to prevent or minimize pain and distress, many painful procedures in the NICU are performed without analgesia. 1. In the study by Simons et al. (2003), many of the procedures were rated by physicians and nurses to be painful (>4 on a 10-point scale); however, very few infants received any pharmacologic or nonpharmacologic procedural pain management. 2. Johnston and colleagues (2011) reported that 46% of tissue-damaging procedures (e.g., heel lance, venipuncture, lumbar puncture, endotracheal intubation, and ophthalmologic examination) and 57% of non–tissue-damaging procedures (e.g., endotracheal suctioning, tape removal, nasogastric tube insertion, catheter removal) were performed without analgesic interventions. 3. A descriptive survey of nurses and physicians noted that, rather than lack of knowledge, the most common reasons for withholding analgesia were related to fear of adverse drug reactions, absence of a unit pain policy, inadequate staffing, poor interdisciplinary communication about timing of procedures, forgetfulness, and taking advantage of the fact that “babies cannot protest” (Akuma and Jordan, 2012). 4. In a study by Johnston and colleagues (2011), parental presence predicted the use of sweet taste analgesia or nonpharmacologic interventions for tissue-damaging procedures. E. Procedural pain guidelines are available to help clinicians choose the most effective and safe pain control measures based on best evidence (Anand and International Evidence-Based Group for Neonatal Pain, 2001; Lago et al., 2009; Spence et al., 2010). b. Spring-loaded mechanical lancets result in less bruising, less need for repeat punctures, and fewer behavioral and physiologic signs of pain. c. Heel warming has no effect on facilitating blood flow during the heel-stick procedure. d. Use of EMLA cream is not effective for management of pain associated with the heel-stick procedure. e. Evidence-based interventions include pacifier with sucrose, swaddling, containment, facilitated tucking, breastfeeding, and skin-to-skin contact with mother. 2. Venipuncture. b. Use smallest-gauge trocar cannula, whenever possible. c. Evidence-based interventions include swaddling, facilitated tucking, pacifier with sucrose, and topical anesthetic cream in infants ≥37 weeks of gestation. 3. Lumbar puncture. b. Evidence-based interventions include sucrose, pacifier, and topical anesthetic cream in infants ≥37 weeks of gestation. 4. Chest tube insertion. b. If infant is intubated and ventilated, administer a slow IV opiate bolus such as fentanyl before the procedure. 5. Endotracheal intubation (Kumar et al. and Committee on Fetus and Newborn, Section on Anesthesiology and Pain Medicine, American Academy of Pediatrics, 2010). b. Premedication with analgesic agents alone or in combination with vagolytic agents, muscle relaxants, or sedatives should be given. c. Using appropriate analgesia and sedation reduces potentially harmful physiologic fluctuations and pain, decreases the time and number of attempts, and minimizes the potential for intubation-related airway trauma. 6. Ophthalmologic exam screening for retinopathy of prematurity. b. Retinal surgery should be considered major surgery, and opiates should be provided. F. Technician expertise, such as the skill of the operator, influences pain responses in infants and should be monitored. Ensuring staff competence to perform required procedures may reduce the number of painful procedures to which an infant is exposed by reducing the number of failed attempts (Simons et al., 2003). A. An understanding of the physiology of acute pain in preterm neonates is essential for optimal pain management in the NICU. Pain responses exhibited by neonates are the result of a concurrent set of reactions within the peripheral nervous system, spinal cord, and higher centers involved at the supraspinal/integrative level, including the thalamus and cerebral cortex (Melzack, 1996). 1. Peripheral nervous system (Evans, 2001). a. Fully mature and functional by 20 weeks of gestation. b. Consists of two types of neuronal afferent fibers. (2) C fibers: polymodal, unmyelinated, slow-conducting fibers associated with aching, burning, poorly localized, or “second pain.” c. Density of nociceptors is equal to or greater than that in adult skin. d. Local tissue injury such as heel stick or venipuncture activates nociceptors of sensory afferent fibers to: (1) Transmit pain impulses to spinal cord and central nervous system (CNS). (2) Release biochemical mediators such as substance P and prostaglandins, which results in hyperalgesia (increased sensitivity to painful stimuli) or allodynia (pain caused by a stimulus that ordinarily does not cause pain). This decreased pain threshold may persist for days or weeks. (3) Cause dendritic sprouting and hyperinnervation that result in hypersensitivity and lower pain threshold that may persist into adulthood. 2. Spinal cord (Evans, 2001). b. Receptive fields of the dorsal horn cells are larger than those of adults and begin to diminish 2 weeks after birth. c. Local spinal cord response to pain impulses from peripheral afferent fibers stimulates efferent somatomotor neurons in the anterior horn and produce reflex withdrawal. d. Afferent fiber neurotransmitters stimulate N-methyl-D-aspartate and tachykinin receptors in the dorsal horns, producing central sensitization (increased excitability of dorsal horn neurons that spreads to several adjacent segments of the spinal cord), “wind-up” phenomenon (perceived increase in intensity or duration of painful stimuli), or secondary hyperalgesia (hypersensitivity elicited by both painful and nonpainful stimuli that extends to areas beyond the site of injury). e. Increases in autonomic responses such as heart rate and respiratory rate and facial responses such as brow bulge, eye squeeze, and nasolabial furrow in response to heel-stick procedures provide evidence of maturity of ascending pathways by 20 weeks of gestation. f. Preterm infants have a limited ability to modulate pain. Dopamine and norepinephrine are not available to modulate pain before 36 to 40 weeks of gestation. Serotonin is first released at approximately 6 to 8 weeks after birth. 3. Supraspinal/integrative level (Evans, 2001). a. Cerebral cortex has a full complement of neurons by 20 weeks of gestation. b. Cerebral cortex is functionally mature by 22 weeks of gestation and bilaterally synchronous by 27 weeks of gestation. c. Somatosensory evoked potentials are slow and simple before 29 weeks of gestation, but short and complex by 40 weeks of gestation. d. Cortical cell migration is complete at approximately 24 weeks of gestation. However, the support structure of the germinal matrix remains highly vascular until 28 weeks. Therefore, the neonate is vulnerable to intraventricular hemorrhage related to increases in blood pressure associated with pain. e. Maximum number of cortical neurons is reached at 28 weeks of gestation, and then approximately 70% of cortical neurons are lost before birth through apoptosis. f. Neonates as early as 27 weeks of gestation can differentiate touch (sham heel stick) from a noxious stimulus (heel stick) as evidenced by physiologic and facial response patterns. g. Neurologic connections are in place for the perception of, reaction to, and memory of pain on the cortical level as evidenced by mature visual and auditory response patterns on electroencephalogram in infants younger than 30 weeks of gestation and by measurements of in-vivo cerebral glucose in the sensory areas of the brain. B. Repetitive, unrelieved pain can lead to serious and adverse consequences for neonates. 2. Pain can cause elevation in intracranial pressure, thereby increasing risk of intraventricular hemorrhage in preterm neonates. 3. Pain and stress may also depress the immune system and contribute to increased susceptibility of neonates to infections. 4. The long-term effects of pain in animals are clear, with changes observed in pain thresholds, social behaviors, stress responses, and pain responses to nonpainful stimuli (Fitzgerald and Anand, 1993; Plotsky et al., 2000; Reynolds et al., 1997; Ruda et al., 2000). Preliminary human data suggest that early pain experiences may impair brain development and alter future pain responses (Bouza, 2009; Brummelte et al., 2012). Johnston and Stevens (1996) reported that neonates who were born at 28 weeks of gestation and were hospitalized in an NICU for 4 weeks (32 weeks of postconceptional age) had decreased behavioral response and significantly higher heart rate and lower oxygen saturation during a heel-stick procedure compared with newly born neonates at 32 weeks of gestation. In another study, Taddio and colleagues (1995) reported that males circumcised within 2 days of birth had significantly longer crying bouts and higher pain intensity scores at immunization at 4 or 6 months of age than males who were not circumcised. A. Recognition of the widespread inadequacy of pain management promoted various professional organizations to issue position statements and clinical recommendations in an effort to promote effective pain management in undertreated populations. Organizations that support the importance of optimal pain assessment and management in hospitalized neonates include the National Association of Neonatal Nurses (Walden and Gibbins, 2012) and the American Academy of Pediatrics and Canadian Paediatric Society (2000, 2006). There is considerable consistency in the recommendations set by these professional organizations. Core principles contained within these guidelines and standards that are applicable to pain assessment and management in the NICU include the following: 1. Assess education and competency in pain assessment and management of new and current employees. 2. Regularly assess and reassess pain using a valid and reliable multidimensional pain assessment instrument. 3. Use both nonpharmacologic and pharmacologic approaches to prevent and/or manage pain. 4. Health care team members should collaborate together and with the infant’s family in developing an approach to pain assessment and management. 5. Documentation should facilitate regular reassessment and follow-up intervention. 6. Policies and procedures should be established to provide consistency and quality of pain assessment and management practices. 7. Data should be collected to monitor the appropriateness and effectiveness of pain management practices. B. The clinical challenge remains on how to implement these standards in various institutional settings based on patient types, frequently occurring clinical procedures performed, and current staffing patterns. A. Pain assessment has been advocated as the “fifth vital sign” and should be assessed routinely. B. “The ‘golden rule’ of pain assessment must be: What is painful to an adult is painful to an infant until proven otherwise” (Franck, 1989). This rule, along with the use of valid and reliable tools, must be used for the assessment of and intervention for pain. C. Because previous painful experiences may modify pain expression, further research is needed to develop and test an instrument to assess chronic pain in the infant requiring prolonged hospitalization who has been subjected to multiple painful clinical procedures. D. Pain assessment is an essential prerequisite to optimal pain management. E. Behavioral responses. 2. Acoustic and temporal characteristics of pain cries are different than other cry types in both preterm and full-term infants, including increases in peak fundamental frequency (pitch), peak spectral energy, cry duration, and intensity. However, differences in cry types are difficult to discriminate in the clinical setting. 3. Many preterm infants do not cry in response to a noxious stimulus. The absence of response may only indicate the depletion of response capability and not lack of pain perception. 4. Healthy full-term newborns use swiping motions by the unaffected leg to the lanced foot, as if trying to push away the noxious stimulus. 5. Preterm infants demonstrate an increase in motor extension patterns, including finger splay, “saluting,” and “sitting on air” during painful clinical procedures. These hyperextension motor patterns are quickly replaced with flaccidity in infants at younger postconceptional ages. F. Physiologic responses. 2. Although physiologic measures provide greater objectivity in the assessment of pain, they also reflect the body’s nonspecific response to stress and thus are not specific to pain (Ranger et al., 2007). Therefore, physiologic measures should be converged with behavioral measures that have been demonstrated to be more consistent and specific to pain in neonates. 3. Physiologic measures should be used to assess pain in infants who are paralyzed for mechanical ventilation or who are severely neurologically impaired. Increases in heart rate and blood pressure during handling generally indicate the need for more analgesia and/or sedation in the pharmacologically paralyzed infant. 4. If the infant is sedated, variability in heart rate and blood pressure decreases. However, it is important to remember that, although sedatives may mask physiologic and behavioral signs of pain, sedatives do not provide pain relief. G. Contextual factors modifying pain responses. 2. Infants in awake or alert states demonstrate a more robust reaction to painful stimuli than infants in sleep states. 3. Research examining facial as well as bodily activity has demonstrated that the magnitude of infant response has been observed to be less vigorous and robust with decreasing postconceptional age. Craig and colleagues (1993) suggested that the less vigorous responses demonstrated by preterm infants “should be interpreted in the context of the energy resources available to respond and the relative immaturity of the musculoskeletal system” (p. 296). 4. Less mature behavioral responses to noxious stimuli are also noted with increased number of painful procedures to which the infant is exposed, increased postnatal age of the infant at time of observation, and shorter length of time since last painful procedure (Ranger et al., 2007). 5. When pain stimuli or pain persists for hours or days without intervention, the infant exhibits a decompensatory response. The sympathetic nervous system, or the “fight-or-flight” mechanism, can no longer compensate. As a result, the physiologic parameters return to baseline (Hummel and van Dijk, 2006). Return to baseline does not indicate that pain is no longer felt or is tolerated, but it does make the infant’s pain more difficult to evaluate. A. Select a composite or multidimensional instrument that incorporates both physiologic and behavioral measures of pain. Caregivers should select instruments with tested reliability, validity, and clinical utility. Infant population, setting, and type of pain experienced should also guide selection of a pain instrument (Duhn and Medves, 2004). B. CRIES: a postoperative pain tool (Table 16-1) (Krechel and Bildner, 1995). 2. Demonstrates validity and interrater reliability for use in infants born at 32 weeks of gestation and later. Initial establishment of clinical utility. 3. Tool scoring system, 0 to 10, is structured in the same fashion as the Apgar score and was designed to make the tool easy to use and remember. 4. Score was originally developed to assess postoperative pain, but has also been used in research related to procedural pain (Ahn, 2006; Belda et al., 2004). 5. A score of 4 or above indicates pain, and any assessment of 4 or above should receive pain intervention. The neonate should then be reevaluated 15 to 30 minutes after analgesia to assess for pain relief. TABLE 16-1 CRIES: Neonatal Postoperative Pain Measurement Score*
Pain Assessment and Management
DEFINITION OF PAIN
NEONATAL INTENSIVE CARE UNIT PROCEDURES THAT CAUSE PAIN
PHYSIOLOGY OF ACUTE PAIN IN PRETERM NEONATES
STANDARDS OF PRACTICE
PAIN ASSESSMENT
PAIN ASSESSMENT INSTRUMENTS
Score
Tips for Scoring CRIES
0
1
2
Crying
No
High pitched
Inconsolable
Score 0: no cry or cry not high pitched
Score 1: high-pitched cry, but consolable
Score 2: high-pitched cry, inconsolable
Requires O2 for saturation >95%
No
<30%
>30%
Score 0: no oxygen required from baseline
Score 1: oxygen requirement <30% from baseline
Score 2: oxygen requirement >30% from baseline
Increased vital signs
HR and BP ≤ preoperative values
HR or BP <20% of preoperative values
HR or BP ≥20% of preoperative values
Score 0: HR and BP are both unchanged or at less than baseline
Score 1: HR or BP is increased by <20%
Score 2: HR or BP is increased by >20%
Note: Measure BP last so as not to wake the infant.
Expression
None
Grimace
Grimace/grunt
Score 0: no grimace
Score 1: grimace only is present
Score 2: grimace and inaudible grunt present
Note: Grimace consists of lowered brow, eyes squeezed shut, deepening nasolabial furrow, and open lips and mouth.
Sleepless
No
Wakes at frequent intervals
Constantly awake
Score 0: continuously asleep
Score 1: awakens at frequent intervals
Score 2: awake constantly
Note: Based on infant’s state during previous hour. 
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