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Pain in Premature Infants: What Is Conclusive Evidence and What Is Not
Newborn & Infant Nursing Reviews 13 (2013) 82–86
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Newborn & Infant Nursing Reviews journal homepage: www.nainr.com
Pain in Premature Infants: What Is Conclusive Evidence and What Is Not Lina Kurdahi Badr RN, DNSc CPNP, FAAN ⁎ Azusa Pacific University, Azusa, CA
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Keywords: Pain assessment Premature infants Neonatal Pain assessment tools
a b s t r a c t Premature infants spend much of their early days of life in an environment that is stressful and in many situations painful. Short and long term consequences of pain are not well documented, yet postulated to have a negative impact on stress-response systems and on deployment. To date there is insufficient evidence for the best methods to assess or to effectively treat their pain. Though a variety of uni- and multidimensional assessment tools are available, many lack sufficient psychometric testing, do not incorporate essential developmental cues to premature infants, and do not distinguish between acute and chronic pain. This review paper will discuss the etiology, sources, and manifestations of pain as well as the short and long term consequences of pain. The available assessment tools for pain in premature infants along with reliability and validity will also be presented. © 2013 Elsevier Inc. All rights reserved.
Pain in Premature Infants Not long ago health professionals believed that neonates, especially premature infants do not feel pain due to the immaturity of the central nervous system. This belief prevailed for decades with small and sick infants subjected to intense pain with no appropriate management. Unfortunately this belief prevails to date in some developing countries. This is despite the fact that over 20 years ago, researchers from Europe and the United States have established the fact that the anatomical, physiological and neurochemical structures that convey pain are well developed in neonates. 1–4 Number of Painful Procedures Pain is experienced by all preterm infants in the neonatal intensive care unit (NICU) as they are exposed to many diagnostic and therapeutic procedures that are necessary for their survival. 5 Studies across nations have reported wide variations in the number of painful procedures premature infants are exposed to (see Table 1). For example, a study in France reported that on average, infants in the NICU experience 115 painful procedures in a 2-week period 6 and a study in Switzerland identified 38,626 procedures performed on 120 preterm infants in a 2-week period with 75% of those considered painful (238 painful procedures per child in 2 weeks) with most occurring in infants with the lowest gestational age. 7 Simons et al. 5 followed 151 neonates for the first 14 days of their NICU admission and documented almost 20,000 pain-producing procedures, of which, 31% were due to repeat attempts when the first procedure failed. This
⁎ Address correspondence to Lina Kurdahi Badr, RN, DNSc CPNP, FAAN, Professor Emerita, UCLA, 4828 Denny Ave., N Hollywood, CA 91601. E-mail address: [email protected]. 1527-3369/1302-0504$36.00/0 – see front matter © 2013 Elsevier Inc. All rights reserved. http://dx.doi.org/10.1053/j.nainr.2013.03.002
averaged 196 procedures per neonate, or between 12 and 15 procedures per day. Three further studies reported an average of two to five painful procedures per day. 8–10 The discrepancy in the numbers of painful procedures among studies could be due to what is considered a painful procedure as well as the different gestational ages of the infants studied and the level of the NICU (see Table 2). For example, the study mentioned above by Cignacco et al. 7 described manipulation of the CPAP prongs or insertion of a nasogastric tube as painful procedures which were not documented as such in other studies. Likewise, a study in Lebanon observed that infants in the NICU were subjected to an average of 14 to 25 procedures per day (280 procedures per child in a 2-week period). Procedures considered as minimally painful such as bathing, and the administration of oral medications and loud noises resulted in significant physiological changes as did more painful procedures such as suctioning and heel sticks. 11 Sources of Pain Painful interventions most studied include capillary blood sampling by heel stick, or venipuncture, (e.g., 5,12–14) followed by naso- or endotracheal suctioning. 15,16 Other painful procedures assessed include placing a nasogastric tube, 17 removing an adhesive tape or monitoring leads, 18 weighing, 19 and eye examination. 20 Contrary to common practice a Cochrane review of six studies (n = 478) found that venipuncture was less painful than the heel stick procedure. The authors conclude that venipuncture should be the preferred mode for blood sampling in term neonates especially if performed by skilled phlebotomist. 21 A study by Goubet and colleagues 22 supports this finding as heel sticks elicited more behavioral distress than venipunctures in a sample of 51 preterm infants. Of interest are two studies that indicated that daily routine activities such as bathing and diaper change can be interpreted as painful to the premature infant as
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Table 1 Number of Painful Procedures Documented in the Literature.
Author (Year), Reference
Subjects, Gestational Age (GA) in Weeks
Baker and Rutter (1995)8
N = 54, GA = 23–41
Zahr and Balian (1995)11
N = 55, GA = 23–32
Stevens et al., (2003)10
N = 194, GA = 27–31; high and low risk N = 151, GA = 25–42
Simons et al., (2003)
5
Johnston et al., (1997)9 Cignacco et al., (2009)7
N = 239, GA = 23–42 N = 120, GA = 24–27
Carbajal et al., (2008)6
N = 430, GA = 24–42
Most Common Procedure in Order of Frequency
Number of Painful Procedures⁎ 3000 procedures total in 3 months. No report of LOS†. 74% in infants less than 31 weeks' gestation 14–25 procedures per infant per day or 273 in 2 weeks (these included daily activities such as diaper change and weighing) Average 10 procedures per infant per day or 140 in 2 weeks. Most procedures were done on the high-risk infants. 19,674 procedures in 1375 days (14.3 per infant per day or 200 in 2 weeks); 31% due to repeated attempts 2134 procedures (1.99 per infant per day or 28 in 2 weeks) 38,626 procedures in the first 14 days (17.3 per day or 242 in 2 weeks) 60,969 procedures in 2 weeks (12 per infant per day or 168 in 2 weeks)
56% heel stick; 26% endotracheal suction Suctioning‡; heel stick; intravenous starts attempts; positioning/Diaper change Suctioning; heel sticks; intravenous starts attempts 63% suctioning followed by heel stick Heel stick followed by insertion of an IV line 26% CPAP manipulation; 17% heel stick 28% suctioning; 19% heel stick
⁎ Number of procedures calculated per day or week when possible. † LOS = length of hospital stay. ‡ Actual percent not reported.
manifested by significant decreases in oxygen saturations (SO2) and increases in heart rates (HR). 11,23 In contrast, Cignacco et al. 7 listed diaper change as a non-painful procedure. In this latter study, 27 procedures common in the NICU were recorded, some procedures (eg. intubation, eye examination, heel stick) were considered to be very painful, some were considered painful (e.g., CPAP prong insertion, extubation, tape removal) and some were labeled as not painful (e.g., diaper change, X-ray, insertion of an umbilical line). Thus, it remains unclear as to what constitutes a painful experience for premature infants. It is also uncertain which factors heighten or dampen responses to pain. The influence of circumstantial factors on the expression of pain, such as the gestational age (GA) of the infant, the severity of illness, the level of sedation or the amount of noise or light in the NICU has not yet been adequately explained. 24 Potential Short- and Long-Term Consequences of Pain Because premature infants cannot manifest pain as well mature infants due to lack of inhibitory control they may be at an increased risk for negative brain alterations in both structure and function. 25
Studies have documented and postulated several neurodevelopmental consequences such as learning and behavioral difficulties observed in later infancy and childhood and reduced brain white matter. 26–29 In contrast, a new longitudinal study with 90 infants who were given either continuous morphine or placebo while in the NICU and followed up at 5 years showed minimal differences between groups. After correcting for contextual variables, children at 5 years were tested for intelligence, visual motor integration, behavior, chronic pain, and health-related quality of life with no difference between groups except for scores on one IQ subtest, “visual analysis.” 30 Thus, the long-term effects of treating pain with morphine or not treating were not any different in this study. The inconsistencies in results could be due to many factors that contribute to the long-term effects of pain such as developmental maturity of the infant at the time pain occurred, GA, illness severity, length of exposure to pain, and contextual variables factors at the time and after the pain exposure. A recent study using EEG recordings during noxious stimuli found that infants who are born prematurely, and who have experienced at least 40 days of intensive or special care, have an increased neuronal response to noxious stimuli compared to healthy newborns at the
Table 2 Commonly Used Pain Assessment Tools for Premature Infants. Neonatal Infant Pain Scale (NIPS) (6 items coded 0–1), behavioral and 1 item breathing Neonatal Facial coding System (NFCS) (9 items coded 0–1), behavioral and physiologic
Lawrence et al., (1993)55
Inter-rater r = .92–.97 Cronbach's α = .87–.95
Granau and Craig (1997)56
Inter-rater, r = .85–.95 Kappa r = .67 Cronbach's α = .83
The Bernese Pain Scale for Neonates (BPSN) (9 items coded 0–3), Behavioral
Cignacco et al., (2004)57
Inter-rater, r = .86–.97
Premature Infant Pain Profile (PIPP) (6 Items coded 1–4), behavioral and physiologic and GA Neonatal Pain Agitation and sedation scale (N-PASS) (8 Items coded −2 to +2), behavioral and physiologic and GA CRIES (5 items coded 0–2), behavioral and physiologic The Douleur Aigue Nouveau-ne (DAN) (13 items coded 0–4), behavioral
Stevens et al., (1996)58
Inter-rater r = .85–.95 Cronbach's α = .82
Hummel et al., (2003)59
Inter-rater = .85– .95 Cronbach's α = .87–.91
Krechel and Bildner (1995)60 Carbajal (1997)61
Inter-rater, r = .72– .98 Kappa r = .93 Inter-rater, r = .59–.97 Cronbach's α = .88
⁎ GA: gestational age. † VAS: visual analogue scale. ‡ FANS: Faceless Acute Neonatal Pain Scale.
Concurrent With VAS⁎ r = .53–.84 Construct Predictive Discriminate Convergent r = .89 Construct F = 41.3, p b .001 Concurrent with VAS† r = .85 and with PIPP r = .91 Discriminate validity t = 2.4, p b .01 Construct r = .85 Concurrent with PIPP, r = .83 Discriminate, t = .2.78, p b .001 Concurrent with NIPS r = .84 Face Concurrent with FANS‡ r = .88
Procedural pain Limited clinical use Preterm and full-term Mostly for research as videotape is needed Procedural pain 25 weeks to full-term Pain Preterm and full-term Procedural pain (most commonly used tool in research) 28–40 weeks For ongoing pain Includes sedation 23–40 weeks Mostly for postoperative pain 32–60 weeks Procedural and prolonged pain Research and clinical use 26–36 weeks
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same corrected age. 31 Another study, which assessed 86 infants between 24-36 weeks gestation with 3-dimensional magnetic resonance spectroscopic imaging, found that procedural pain was associated with reduced white matter and reduced sub cortical grey matter. 25 These findings are supported by data from animal models suggesting that prolonged exposure to pain influences the normal development of the nociceptive neural circuits and leads to lowered pain thresholds during later infancy and decreased withdrawal latencies to intense heat. 25,32 It has been suggested that intense or prolonged pain in premature infants may increase their risk for a brain injury by increasing intracranial pressure and oxygen desaturation from pain may lead to generation of free radicals that can damage fast-growing brain tissue. 33–35 To date the long-term consequences of short- and long-term exposure to pain in premature infants remain questionable. Manifestations of Pain Neonatal pain is manifested through behavioral signs such as facial expressions, body movements, crying, and consolability 36,37 and physical signs such as hypoxemia, hypertension, tachycardia, a rise of heart rate variability (HRV), and an increase in cortisol levels. 38–40 However, it should be noted that behavioral signs may not correlate with the intensity of the painful event. For example, researchers have noted that premature infants who are exposed to repeated painful experiences may experience less heightened responses to pain or be desensitized to pain. 41–43 This can be explained by the differences between acute and chronic pain. In acute pain psychophysiological changes (increased HR, respiratory rate, [RR] blood pressure, and decreased SO2) occur as well as behavioral changes (crying, body movements and facial expressions), In chronic pain there is a dampening of normal behavioral and physiological responses. 43 In support of this an earlier study by Fitzgerald et al. 44 noted that the flexion reflex threshold of the foot where the heel sticks were done was lower than the threshold of the other intact foot, indicating sensitization after repeated experience with painful procedures and possibly altered excitability of the spinal cord. Johnston and colleagues 41 assessed the reaction of preterm infants to the heel stick procedure over an 8-week period and found no significant changes in heart rate and oxygen saturation over time, but did find an increase in facial expressions of pain. In contrast, baseline HR increased significantly for VLBW infants from 24 to 32.7 weeks during a heel lanced blood draw procedure and decreased thereafter. The inconsistencies in results among studies are probably due to the difference in the GAs of infants, the different kinds of painful procedures infants were exposed to and the different assessment tools used. Pain Assessment To adequately determine the presence or the intensity of pain adequate assessment instruments are necessary. However, due to the limited verbal capacity of the infant it is important to recognize that pain measures are limited in distinguishing between pain and distress. 42,43 Very small preterm infants may not respond vigorously to painful stimuli because of the immaturity of their motor and nervous systems. In addition, preterm infants at earlier GAs may not display the same behaviors in response to pain as those born at later gestational ages. Although, several instruments over the last decade have contributed to the satisfactory, albeit not the precise assessment of pain in the premature infant, 4,47–50 no one instrument has sufficient reliability, validity and sensitivity. In addition most instruments have been developed for research utilization and have little clinical application. Pain has been assessed using unidimensional indicators (either physical or behavioral) or multidimensional indicators (both physical
and behavioral). Since physical and behavioral indicators have not been reported to have a high correlation, 42,50,51 most researchers recommend the multidimensional approach to pain assessment. 52 In contrast, a review of assessment instruments by Raeside 53 suggested that the most feasible way to assess pain in infants is by physiological parameters (HR, S02, blood pressure and RR) with only the HR being the most sensitive measure. This dissociation between measures and the lack of consensus on the best method to assess pain has hindered practitioners from figuring out which interventions are beneficial and which are not. More than 40 assessment tools have been published over the years including behavioral assessment tools, such as the Neonatal Infant Pain Scale, 54 the Neonatal Facial Coding System, 55 and the Bernese Pain Scale for neonates, 56 and behavioral and physiologic tools such as the Premature Infant Pain Profile, 57 the Neonatal Pain, Agitation and Sedation Scale, 58 the CRIES 59 and the Douleur Aigue Du nouveau-ne scale. 60 Pain has also been assessed using physiological indicators such salivary and blood cortisol, HR and heart rate variability (HRV), 39,61,62 and newer methods such as near-infrared spectroscopy (NIRS), skin conductance measurements, EEG and resonance spectroscopic imaging. 25,49,63–65 It is worth noting that despite a variety of instruments that assess acute pain, there is no adequate measurement of chronic pain or pain in neurologically or physically impaired infants. Since previous reviews have provided details of available pain assessments tools for preterm infants with documented validity and reliability (e.g., Hummel et al., 49 Lawrence et al., 53 de Oliveira et al., 66 and Duhn et al. 67) this paper provides a brief summary of the most commonly used behavioral tools with the documented reliability and validity of each when available (see Table 2). Conclusion Pain in the NICU setting may be inevitable and may not be entirely avoided. Premature infants, especially the very sick and fragile are exposed to 2 to 17 painful procedures a day, not to mention the routine procedures that may be as noxious. It is now well established that even VLBW infants experience pain though they are not capable of manifesting overt behavioral cues. It behooves nurses to be cognizant of behavioral cues and to have the necessary critical skills to differentiate pain behaviors from other stressful behaviors that occur apart from painful situations. 68 It is also essential that nurses differentiate the responses of preterm infants of differing gestational ages and those who are sedated or not fully conscious. Abundant infant pain measurement tools are available and have documented reliability and validity however, most need further testing for clinical applicability and sensitively. Studies note that while nurses acknowledge that infants experience pain and are familiar with pain assessment tools they may not have adequate knowledge regarding the expression of pain not are assessments routinely used. 68–71 As a result pain management remains unsystematic and capricious. 45–50 This is especially true in NICUs of less developed countries. It is recommended that nurses working in the NICU are educated about pain assessment in order to adequately assess pain in preterm infants on regular basis. The use of the most reliable and valid multidimensional instrument is encouraged taking into consideration practicality and ease of administration. The PIPP scale is the most commonly used scale in research studies as it takes into consideration the gestational age of the infant but it may not be the easiest in terms of ease of administration or clinical utility. The short-term consequences of pain are well documented. An increase in HR, a decrease in SO2, HRV, blood pressure fluctuations and increased secretion of stress hormones are noted in many studies. 52,53 What remains unclear is which factors affect pain responses in individual infants and which contextual variables may enhance or dampen pain responses.
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Furthermore, while studies have quantified the effect of pain in the infant brain, and have postulated that untreated pain can contribute to poor growth and increased time on mechanical ventilation. 71–74 long-term consequences are not as clear. Longterm morbidity may be the result of many variables which makes it difficult to attribute the effect of one single variable. As such detailed RCTs and longitudinal studies that establish case effect relationships are needed.
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Newborn & Infant Nursing Reviews journal homepage: www.nainr.com
Pain in Premature Infants: What Is Conclusive Evidence and What Is Not Lina Kurdahi Badr RN, DNSc CPNP, FAAN ⁎ Azusa Pacific University, Azusa, CA
a r t i c l e
i n f o
Keywords: Pain assessment Premature infants Neonatal Pain assessment tools
a b s t r a c t Premature infants spend much of their early days of life in an environment that is stressful and in many situations painful. Short and long term consequences of pain are not well documented, yet postulated to have a negative impact on stress-response systems and on deployment. To date there is insufficient evidence for the best methods to assess or to effectively treat their pain. Though a variety of uni- and multidimensional assessment tools are available, many lack sufficient psychometric testing, do not incorporate essential developmental cues to premature infants, and do not distinguish between acute and chronic pain. This review paper will discuss the etiology, sources, and manifestations of pain as well as the short and long term consequences of pain. The available assessment tools for pain in premature infants along with reliability and validity will also be presented. © 2013 Elsevier Inc. All rights reserved.
Pain in Premature Infants Not long ago health professionals believed that neonates, especially premature infants do not feel pain due to the immaturity of the central nervous system. This belief prevailed for decades with small and sick infants subjected to intense pain with no appropriate management. Unfortunately this belief prevails to date in some developing countries. This is despite the fact that over 20 years ago, researchers from Europe and the United States have established the fact that the anatomical, physiological and neurochemical structures that convey pain are well developed in neonates. 1–4 Number of Painful Procedures Pain is experienced by all preterm infants in the neonatal intensive care unit (NICU) as they are exposed to many diagnostic and therapeutic procedures that are necessary for their survival. 5 Studies across nations have reported wide variations in the number of painful procedures premature infants are exposed to (see Table 1). For example, a study in France reported that on average, infants in the NICU experience 115 painful procedures in a 2-week period 6 and a study in Switzerland identified 38,626 procedures performed on 120 preterm infants in a 2-week period with 75% of those considered painful (238 painful procedures per child in 2 weeks) with most occurring in infants with the lowest gestational age. 7 Simons et al. 5 followed 151 neonates for the first 14 days of their NICU admission and documented almost 20,000 pain-producing procedures, of which, 31% were due to repeat attempts when the first procedure failed. This
⁎ Address correspondence to Lina Kurdahi Badr, RN, DNSc CPNP, FAAN, Professor Emerita, UCLA, 4828 Denny Ave., N Hollywood, CA 91601. E-mail address: [email protected]. 1527-3369/1302-0504$36.00/0 – see front matter © 2013 Elsevier Inc. All rights reserved. http://dx.doi.org/10.1053/j.nainr.2013.03.002
averaged 196 procedures per neonate, or between 12 and 15 procedures per day. Three further studies reported an average of two to five painful procedures per day. 8–10 The discrepancy in the numbers of painful procedures among studies could be due to what is considered a painful procedure as well as the different gestational ages of the infants studied and the level of the NICU (see Table 2). For example, the study mentioned above by Cignacco et al. 7 described manipulation of the CPAP prongs or insertion of a nasogastric tube as painful procedures which were not documented as such in other studies. Likewise, a study in Lebanon observed that infants in the NICU were subjected to an average of 14 to 25 procedures per day (280 procedures per child in a 2-week period). Procedures considered as minimally painful such as bathing, and the administration of oral medications and loud noises resulted in significant physiological changes as did more painful procedures such as suctioning and heel sticks. 11 Sources of Pain Painful interventions most studied include capillary blood sampling by heel stick, or venipuncture, (e.g., 5,12–14) followed by naso- or endotracheal suctioning. 15,16 Other painful procedures assessed include placing a nasogastric tube, 17 removing an adhesive tape or monitoring leads, 18 weighing, 19 and eye examination. 20 Contrary to common practice a Cochrane review of six studies (n = 478) found that venipuncture was less painful than the heel stick procedure. The authors conclude that venipuncture should be the preferred mode for blood sampling in term neonates especially if performed by skilled phlebotomist. 21 A study by Goubet and colleagues 22 supports this finding as heel sticks elicited more behavioral distress than venipunctures in a sample of 51 preterm infants. Of interest are two studies that indicated that daily routine activities such as bathing and diaper change can be interpreted as painful to the premature infant as
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Table 1 Number of Painful Procedures Documented in the Literature.
Author (Year), Reference
Subjects, Gestational Age (GA) in Weeks
Baker and Rutter (1995)8
N = 54, GA = 23–41
Zahr and Balian (1995)11
N = 55, GA = 23–32
Stevens et al., (2003)10
N = 194, GA = 27–31; high and low risk N = 151, GA = 25–42
Simons et al., (2003)
5
Johnston et al., (1997)9 Cignacco et al., (2009)7
N = 239, GA = 23–42 N = 120, GA = 24–27
Carbajal et al., (2008)6
N = 430, GA = 24–42
Most Common Procedure in Order of Frequency
Number of Painful Procedures⁎ 3000 procedures total in 3 months. No report of LOS†. 74% in infants less than 31 weeks' gestation 14–25 procedures per infant per day or 273 in 2 weeks (these included daily activities such as diaper change and weighing) Average 10 procedures per infant per day or 140 in 2 weeks. Most procedures were done on the high-risk infants. 19,674 procedures in 1375 days (14.3 per infant per day or 200 in 2 weeks); 31% due to repeated attempts 2134 procedures (1.99 per infant per day or 28 in 2 weeks) 38,626 procedures in the first 14 days (17.3 per day or 242 in 2 weeks) 60,969 procedures in 2 weeks (12 per infant per day or 168 in 2 weeks)
56% heel stick; 26% endotracheal suction Suctioning‡; heel stick; intravenous starts attempts; positioning/Diaper change Suctioning; heel sticks; intravenous starts attempts 63% suctioning followed by heel stick Heel stick followed by insertion of an IV line 26% CPAP manipulation; 17% heel stick 28% suctioning; 19% heel stick
⁎ Number of procedures calculated per day or week when possible. † LOS = length of hospital stay. ‡ Actual percent not reported.
manifested by significant decreases in oxygen saturations (SO2) and increases in heart rates (HR). 11,23 In contrast, Cignacco et al. 7 listed diaper change as a non-painful procedure. In this latter study, 27 procedures common in the NICU were recorded, some procedures (eg. intubation, eye examination, heel stick) were considered to be very painful, some were considered painful (e.g., CPAP prong insertion, extubation, tape removal) and some were labeled as not painful (e.g., diaper change, X-ray, insertion of an umbilical line). Thus, it remains unclear as to what constitutes a painful experience for premature infants. It is also uncertain which factors heighten or dampen responses to pain. The influence of circumstantial factors on the expression of pain, such as the gestational age (GA) of the infant, the severity of illness, the level of sedation or the amount of noise or light in the NICU has not yet been adequately explained. 24 Potential Short- and Long-Term Consequences of Pain Because premature infants cannot manifest pain as well mature infants due to lack of inhibitory control they may be at an increased risk for negative brain alterations in both structure and function. 25
Studies have documented and postulated several neurodevelopmental consequences such as learning and behavioral difficulties observed in later infancy and childhood and reduced brain white matter. 26–29 In contrast, a new longitudinal study with 90 infants who were given either continuous morphine or placebo while in the NICU and followed up at 5 years showed minimal differences between groups. After correcting for contextual variables, children at 5 years were tested for intelligence, visual motor integration, behavior, chronic pain, and health-related quality of life with no difference between groups except for scores on one IQ subtest, “visual analysis.” 30 Thus, the long-term effects of treating pain with morphine or not treating were not any different in this study. The inconsistencies in results could be due to many factors that contribute to the long-term effects of pain such as developmental maturity of the infant at the time pain occurred, GA, illness severity, length of exposure to pain, and contextual variables factors at the time and after the pain exposure. A recent study using EEG recordings during noxious stimuli found that infants who are born prematurely, and who have experienced at least 40 days of intensive or special care, have an increased neuronal response to noxious stimuli compared to healthy newborns at the
Table 2 Commonly Used Pain Assessment Tools for Premature Infants. Neonatal Infant Pain Scale (NIPS) (6 items coded 0–1), behavioral and 1 item breathing Neonatal Facial coding System (NFCS) (9 items coded 0–1), behavioral and physiologic
Lawrence et al., (1993)55
Inter-rater r = .92–.97 Cronbach's α = .87–.95
Granau and Craig (1997)56
Inter-rater, r = .85–.95 Kappa r = .67 Cronbach's α = .83
The Bernese Pain Scale for Neonates (BPSN) (9 items coded 0–3), Behavioral
Cignacco et al., (2004)57
Inter-rater, r = .86–.97
Premature Infant Pain Profile (PIPP) (6 Items coded 1–4), behavioral and physiologic and GA Neonatal Pain Agitation and sedation scale (N-PASS) (8 Items coded −2 to +2), behavioral and physiologic and GA CRIES (5 items coded 0–2), behavioral and physiologic The Douleur Aigue Nouveau-ne (DAN) (13 items coded 0–4), behavioral
Stevens et al., (1996)58
Inter-rater r = .85–.95 Cronbach's α = .82
Hummel et al., (2003)59
Inter-rater = .85– .95 Cronbach's α = .87–.91
Krechel and Bildner (1995)60 Carbajal (1997)61
Inter-rater, r = .72– .98 Kappa r = .93 Inter-rater, r = .59–.97 Cronbach's α = .88
⁎ GA: gestational age. † VAS: visual analogue scale. ‡ FANS: Faceless Acute Neonatal Pain Scale.
Concurrent With VAS⁎ r = .53–.84 Construct Predictive Discriminate Convergent r = .89 Construct F = 41.3, p b .001 Concurrent with VAS† r = .85 and with PIPP r = .91 Discriminate validity t = 2.4, p b .01 Construct r = .85 Concurrent with PIPP, r = .83 Discriminate, t = .2.78, p b .001 Concurrent with NIPS r = .84 Face Concurrent with FANS‡ r = .88
Procedural pain Limited clinical use Preterm and full-term Mostly for research as videotape is needed Procedural pain 25 weeks to full-term Pain Preterm and full-term Procedural pain (most commonly used tool in research) 28–40 weeks For ongoing pain Includes sedation 23–40 weeks Mostly for postoperative pain 32–60 weeks Procedural and prolonged pain Research and clinical use 26–36 weeks
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same corrected age. 31 Another study, which assessed 86 infants between 24-36 weeks gestation with 3-dimensional magnetic resonance spectroscopic imaging, found that procedural pain was associated with reduced white matter and reduced sub cortical grey matter. 25 These findings are supported by data from animal models suggesting that prolonged exposure to pain influences the normal development of the nociceptive neural circuits and leads to lowered pain thresholds during later infancy and decreased withdrawal latencies to intense heat. 25,32 It has been suggested that intense or prolonged pain in premature infants may increase their risk for a brain injury by increasing intracranial pressure and oxygen desaturation from pain may lead to generation of free radicals that can damage fast-growing brain tissue. 33–35 To date the long-term consequences of short- and long-term exposure to pain in premature infants remain questionable. Manifestations of Pain Neonatal pain is manifested through behavioral signs such as facial expressions, body movements, crying, and consolability 36,37 and physical signs such as hypoxemia, hypertension, tachycardia, a rise of heart rate variability (HRV), and an increase in cortisol levels. 38–40 However, it should be noted that behavioral signs may not correlate with the intensity of the painful event. For example, researchers have noted that premature infants who are exposed to repeated painful experiences may experience less heightened responses to pain or be desensitized to pain. 41–43 This can be explained by the differences between acute and chronic pain. In acute pain psychophysiological changes (increased HR, respiratory rate, [RR] blood pressure, and decreased SO2) occur as well as behavioral changes (crying, body movements and facial expressions), In chronic pain there is a dampening of normal behavioral and physiological responses. 43 In support of this an earlier study by Fitzgerald et al. 44 noted that the flexion reflex threshold of the foot where the heel sticks were done was lower than the threshold of the other intact foot, indicating sensitization after repeated experience with painful procedures and possibly altered excitability of the spinal cord. Johnston and colleagues 41 assessed the reaction of preterm infants to the heel stick procedure over an 8-week period and found no significant changes in heart rate and oxygen saturation over time, but did find an increase in facial expressions of pain. In contrast, baseline HR increased significantly for VLBW infants from 24 to 32.7 weeks during a heel lanced blood draw procedure and decreased thereafter. The inconsistencies in results among studies are probably due to the difference in the GAs of infants, the different kinds of painful procedures infants were exposed to and the different assessment tools used. Pain Assessment To adequately determine the presence or the intensity of pain adequate assessment instruments are necessary. However, due to the limited verbal capacity of the infant it is important to recognize that pain measures are limited in distinguishing between pain and distress. 42,43 Very small preterm infants may not respond vigorously to painful stimuli because of the immaturity of their motor and nervous systems. In addition, preterm infants at earlier GAs may not display the same behaviors in response to pain as those born at later gestational ages. Although, several instruments over the last decade have contributed to the satisfactory, albeit not the precise assessment of pain in the premature infant, 4,47–50 no one instrument has sufficient reliability, validity and sensitivity. In addition most instruments have been developed for research utilization and have little clinical application. Pain has been assessed using unidimensional indicators (either physical or behavioral) or multidimensional indicators (both physical
and behavioral). Since physical and behavioral indicators have not been reported to have a high correlation, 42,50,51 most researchers recommend the multidimensional approach to pain assessment. 52 In contrast, a review of assessment instruments by Raeside 53 suggested that the most feasible way to assess pain in infants is by physiological parameters (HR, S02, blood pressure and RR) with only the HR being the most sensitive measure. This dissociation between measures and the lack of consensus on the best method to assess pain has hindered practitioners from figuring out which interventions are beneficial and which are not. More than 40 assessment tools have been published over the years including behavioral assessment tools, such as the Neonatal Infant Pain Scale, 54 the Neonatal Facial Coding System, 55 and the Bernese Pain Scale for neonates, 56 and behavioral and physiologic tools such as the Premature Infant Pain Profile, 57 the Neonatal Pain, Agitation and Sedation Scale, 58 the CRIES 59 and the Douleur Aigue Du nouveau-ne scale. 60 Pain has also been assessed using physiological indicators such salivary and blood cortisol, HR and heart rate variability (HRV), 39,61,62 and newer methods such as near-infrared spectroscopy (NIRS), skin conductance measurements, EEG and resonance spectroscopic imaging. 25,49,63–65 It is worth noting that despite a variety of instruments that assess acute pain, there is no adequate measurement of chronic pain or pain in neurologically or physically impaired infants. Since previous reviews have provided details of available pain assessments tools for preterm infants with documented validity and reliability (e.g., Hummel et al., 49 Lawrence et al., 53 de Oliveira et al., 66 and Duhn et al. 67) this paper provides a brief summary of the most commonly used behavioral tools with the documented reliability and validity of each when available (see Table 2). Conclusion Pain in the NICU setting may be inevitable and may not be entirely avoided. Premature infants, especially the very sick and fragile are exposed to 2 to 17 painful procedures a day, not to mention the routine procedures that may be as noxious. It is now well established that even VLBW infants experience pain though they are not capable of manifesting overt behavioral cues. It behooves nurses to be cognizant of behavioral cues and to have the necessary critical skills to differentiate pain behaviors from other stressful behaviors that occur apart from painful situations. 68 It is also essential that nurses differentiate the responses of preterm infants of differing gestational ages and those who are sedated or not fully conscious. Abundant infant pain measurement tools are available and have documented reliability and validity however, most need further testing for clinical applicability and sensitively. Studies note that while nurses acknowledge that infants experience pain and are familiar with pain assessment tools they may not have adequate knowledge regarding the expression of pain not are assessments routinely used. 68–71 As a result pain management remains unsystematic and capricious. 45–50 This is especially true in NICUs of less developed countries. It is recommended that nurses working in the NICU are educated about pain assessment in order to adequately assess pain in preterm infants on regular basis. The use of the most reliable and valid multidimensional instrument is encouraged taking into consideration practicality and ease of administration. The PIPP scale is the most commonly used scale in research studies as it takes into consideration the gestational age of the infant but it may not be the easiest in terms of ease of administration or clinical utility. The short-term consequences of pain are well documented. An increase in HR, a decrease in SO2, HRV, blood pressure fluctuations and increased secretion of stress hormones are noted in many studies. 52,53 What remains unclear is which factors affect pain responses in individual infants and which contextual variables may enhance or dampen pain responses.
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Furthermore, while studies have quantified the effect of pain in the infant brain, and have postulated that untreated pain can contribute to poor growth and increased time on mechanical ventilation. 71–74 long-term consequences are not as clear. Longterm morbidity may be the result of many variables which makes it difficult to attribute the effect of one single variable. As such detailed RCTs and longitudinal studies that establish case effect relationships are needed.
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