PEDIATRICS Vol. 110 No. 3 September 2002, pp. 523-528
Routine Sucrose Analgesia During the First Week of Life in Neonates Younger Than 31 Weeks’ Postconceptional Age
* McGill University, Montreal, Canada
Hopital St Justine, Montreal, Canada
IWK-Grace Health Sciences Centre, Halifax, Canada
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ABSTRACT |
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Objective. To determine the efficacy of sucrose analgesia for procedural pain during the first week of life in preterm neonates in neonatal intensive care units on enhancing later clinical outcomes.
Methods. A total of 107 preterm neonates who were born at <31 weeks’ postconceptional age (PCA) entered this double-blind, randomized, controlled trial within 48 hours of birth at 3 level III university-affiliated neonatal intensive care units in Canada, and 103 completed the study. Sucrose (0.1 mL of 24%) or sterile water was administered orally up to 3 times, 2 minutes apart, for every invasive procedure during a 7-day period. Motor development and vigor, and alertness and orientation components of the Neurobehavioral Assessment of the Preterm Infant were measured at 32, 36, and 40 weeks’ PCA; Score for Neonatal Acute Physiology was measured on the last day of intervention; and Neuro-Biological Risk Score (NBRS) was measured at 2 weeks of age and at discharge. Primary analyses of covariance were applied for each outcome to compare group differences followed by secondary analyses using standard linear regression within each group to determine predictors of outcomes.
Results. Although there were no differences between the groups on any outcomes, there were significant dose-related effects within each group. In the sucrose group only, higher number of doses of sucrose predicted lower scores on motor development and vigor, and alertness and orientation at 36 weeks’, lower motor development and vigor at 40 weeks’, and higher NBRS at 2 weeks’ postnatal age. Higher number of invasive procedures was predictive of higher NBRS both times in the water group.
Conclusions. Repeated use of sucrose analgesia in infants <31 weeks’ PCA may put infants at risk for poorer neurobehavioral development and physiologic outcomes. Additional study is needed to determine the most appropriate age and duration of sucrose analgesia in preterm infants.
Key Words: neonate • preterm • pain • sucrose • analgesia
Abbreviations: NICU, neonatal intensive care unit • PCA, postconceptional age • NAPI, Neurobehavioral Assessment of the Preterm Infant • AO, alertness and orientation • MDV, motor development and vigor • SNAP, Score for Neonatal Acute Physiology • NBRS, Neuro-Biological Risk Score • CRIB, Clinical Risk Index for Infants
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INTRODUCTION |
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Sucrose has been reported to have analgesic properties in newborns, both animal and human.1–4 In a systematic review of sucrose analgesia, doses from 0.05 to 2 mL of 12% to 50% sucrose were reported to have analgesic effects in preterm or full-term neonates.5 The mechanism for the analgesic effect is thought to be via the release of endogenous opiates triggered by sweet taste,1, 2, 6 although the salience of a taste is immediately calming and distracting.7 Studies in which other saccharides were tested for analgesic properties provide support for the sweet taste hypothesis. 8–10 Lactose and human milk seem not to have analgesic properties, but they are relatively less sweet than the other sugars studied.11,12 The data supporting the use of sucrose as an analgesic for "minor" painful procedures are sufficiently strong that the American and Canadian Pediatric Societies have recommended the use of sucrose for such procedures as heel lances, injections, and intravenous line insertions.13 This is particularly important for preterm or ill infants in the neonatal intensive care units (NICU) environment, where they undergo multiple invasive, tissue-damaging, and presumably painful procedures daily.14–16 Typically, more of these procedures occur during the first week of life with stabilization and diagnosis of the newborn. There is mounting evidence that untreated procedural pain in newborn preterm infants can alter subsequent behavior, specifically leading to less robust behavioral responses.17, 18
Although the data on the effect of sucrose for a single painful procedure are strongly supportive of the use of sucrose for management of minor procedural pain, the effects of routine use of sucrose analgesia in preterm infants have not been evaluated. Given emerging data on negative behavioral sequelae to untreated procedural pain in preterm neonates, it would be reasonable to hypothesize that if procedural pain were adequately managed in the first week of life in preterm neonates, then there might be positive long-term developmental effects. Therefore, the purpose of this study was to investigate the efficacy of routine sucrose analgesia for procedural pain in the first week of life in preterm infants born at <31 weeks’ postconceptional age (PCA).
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METHODS |
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Sample
Three level III university-affiliated NICUs in Canada were the sites for the study, and each site provided ethics approval by a constituted review board. The sites were similar in level of acuity of the infants and teaching programs. There were differences in level of developmental care: 1 site had completely implemented it, and the other 2 had some components (eg, unit darkened except for morning rounds). One unit treated with indomethacin more than the other units. Infants who were born between 25 and 31 completed weeks’ PCA, were expected to live according to the opinion of the attending neonatologist, were above the fifth percentile weight for gestational age, had intraventricular hemorrhage less than grade 3 and no periventricular leukomalacia, were free of major congenital anomalies, and did not require surgery and whose parents consented within 48 hours of birth were included in the study. Sample size estimates based on the primary outcomes of Neurobehavioral Assessment of the Preterm Infant (NAPI19; see below) were 35 per group for a power of 0.8 with statistical significance set at .05.
Intervention
Enrolled infants were randomly assigned to the sucrose or water group from a computer-generated schedule for each site. Only the project nurses in each site knew the group assignment; treating clinicians were blind to group assignment. Solutions of 0.1 mL of 24% sucrose or water were drawn up into sterile syringes and placed in the unit medicine refrigerator. Every time the infant was to undergo an invasive (eg, heel lance, intravenous cannulation, arterial puncture, injection) or noninvasive but presumably uncomfortable procedure (eg, endotracheal tube suctioning, tape/lead removal, gavage insertion for feeding), the solution in the syringe was administered into the infant’s mouth, at the beginning of the procedure, 2 minutes into the procedure, and another 2 minutes into the procedure. If the procedure was to last >15 minutes, up to another 3 0.1 doses were to be given 2 minutes apart.
In 1 site, there was videotaping of 1 infant at any point in time for the duration of the study week. A small wide-angle lens camera rested on top of the isolette and was connected to a mat on the floor next to the isolette such that stepping on the mat triggered 5-minute recording. The person who approached the infant was to identify his or her role (eg, nurse, mother) and the purpose of his or her approach (eg, suctioning, visiting). In this way, facial actions could be recorded during painful procedures to verify whether there was an immediate analgesic effect of the sucrose. Coding of faces was conducted in the laboratory according to the upper facial components of the Neonatal Facial Coding System.20 Only the upper facial components were coded because many of the infants were intubated and these components have been shown to be specific to pain response in preterm infants.21
Outcomes
The primary outcome was neurobehavioral development assessed by the subscales of alertness and orientation (AO) and motor development and vigor (MDV) of the NAPI developed by Korner and colleagues.19, 22–24 The NAPI is appropriate for infants between 32 weeks’ PCA and term. It assesses the relative maturity of functioning of preterm infants, with higher scores reflecting higher maturity, and can differentiate 2 weeks’ PCA. Much of the examination consists of observational items, and the remainder rates the infant’s response to stimuli. This assessment takes approximately 30 minutes to administer and includes 7 clusters of single-item neurobehavioral dimensions: MDV, scarf sign, popliteal angle, AO, irritability, vigor of crying, and percentage asleep ratings. Test-retest reliability over 2 consecutive days ranged from 0.59 to 0.90. Original interobserver reliability ranged from 0.64 to 0.93.23 The observers in this study were either occupational therapists (L.S., C.L.) or a psychologist (H.C.) with doctoral training and experience with this population. After the viewing of a detailed training tape provided with the NAPI kit, the interrater reliability using the intraclass correlation coefficient was >0.9. The clinical validity and sensitivity of the NAPI were established using an index of medical complications based on a 1 to 5 classification range of degrees of complications.25 Functions that required strength and vigor were significantly related to medical complications, whereas items that assessed AO were not.25, 26 Assessments were conducted at 32, 36, and 40 weeks’ PCA if respirations were unassisted and the infant was available for assessment.
The secondary outcomes were measures of severity of illness during the course of the intervention and at discharge. These were assessed during the week of study by the Score for Neonatal Acute Physiology (SNAP)27, 28 for each 24-hour period and by the Neuro-Biological Risk Score (NBRS)29 at 2 weeks’ postnatal age and at discharge. Background information, including PCA at birth (determined by ultrasound), birth weight, and Apgar, was obtained from the medical record, and the Clinical Risk Index for Infants (CRIB),30–32 an index of severity of illness at birth, was calculated from information in the medical record. Serum glucose levels during the study time were obtained from the medical record when ordered clinically (not for purposes of the study).
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RESULTS |
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Sample
Over the course of 27 months, 281 infants were admitted within the age category. Eighty-one (29.2%) were not evaluated for eligibility for the following reasons: mother too ill to consent within 48 hours, compassionate reasons (twin or triplet sibling had died), or unit difficulties when recruitment was temporarily stopped (Y2K problems, understaffing during holidays or ice storm). Thirty-two (16.3%) did not meet the selection criteria (died within 48 hours, deemed too ill by staff). Of the 168 remaining infants, 107 (63.7%) parents gave consent for the infant to participate. The reasons for the 63 refusals were as follows: the parents thought that the infant was too ill (5), were too stressed to consider study (4), did not want their infant to be in any research (10) or to receive sugar (4), or gave no reason (38). There were no significant differences between excluded infants, infants whose parents refused, and participating infants in the distribution of PCA or weight (Table 1).
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Two infants were withdrawn from the study during the week of intervention. Two other infants died: 1 of grade 4 intraventricular hemorrhage and periventricular leukomalacia on the first day of the study after receiving 1 dose of water and the other infant of cardiac failure associated with patent ductus arteriosus at age 29 days. One infant was withdrawn on study day 4 for hyperglycemia after receiving 10, 6, and 12 doses of sucrose and serum glucose levels of 3.5, 16, and 12 on the respective study days. The infant became septic 48 hours after withdrawal from the study, which may be an alternative explanation for the glucose instability. The second infant was withdrawn from the study for suspected necrotizing enterocolitis. The infant did not develop necrotizing enterocolitis but did have Escherichia coli sepsis. At baseline, there were no group differences in birth PCA, birth weight, or CRIB score (see Table 1), and there were no differences between sites on age, CRIB score, or birth weight (see Table 1). There were differences in amount of indomethacin given to infants at 1 site.
Solutions
The total number of study doses given per infant during the week ranged from 24 to 125 with a mean of 58 in the water group and 63 in the sucrose group. An estimate of compliance in administering solutions was determined by dividing the number of procedures by the number of doses, which was an underestimate because an infant could potentially receive up to 3 doses per intervention. Overall, this estimate was only 69%, ranging widely between 27% and 185%, and was the same for both groups. One site accounted for the lack of compliance that became evident after the first 6 months of study, and this noncompliance persisted despite holding sessions with the nursing staff on the importance of adhering to the protocol. Serum glucose levels ranged from 1.8 to 13.5, but there were no group differences and there was no relationship between the number of solutions and the serum glucose level in either group.
The number of infants whose videotapes were able to be coded throughout the week was small (14) but indicated that the sucrose was effective as an analgesic during the immediate 60 seconds of initiation of the painful procedure, even on day 7.
NAPI
The NAPI was administered to infants who no longer required ventilatory assistance and were not discharged back to distant referring centers. At 32 weeks, 75 infants could be tested, 87 at 36 weeks, and 67 at 40 weeks, with only 53 infants having data at all 3 times. There were, however, at least 35 infants/group at each time, thus meeting the original sample size estimates. Multivariate analysis of covariance was therefore conducted at each age, to maintain the sample size estimates that would not have been met with repeated measures analyses, with covariates of PCA and number of invasive procedures on the 2 components of the NAPI that were tested, MDV and AO. No significant differences were found between the sucrose and water groups (MDV: sucrose at 32, 36, 40 weeks = 20.4, 48.6, 66.1; water at 32, 36, 40 weeks = 21.7, 49.7, 63.9; F(1,52) = 0.223, P = .64; AO: sucrose at 32, 36, 40 weeks = 16.0, 40.7, 54.3; water at weeks 32, 36, 40 = 19.5, 42.2, 55.5; F(1,52) = 2.016, P = .162).
Because compliance with administering solutions was generally low and there was a wide range of compliance, we were interested in determining whether number of doses of sucrose was related to outcomes while accounting for other factors that might be correlated with number of doses. Secondary analyses using standard multiple regressions were conducted by group on each of the NAPI components at each age to determine whether there were background factors, specifically age at birth, CRIB, or other factors related to the NICU experience, such as days on certain medications (sedatives, analgesics, caffeine, indomethacin), number of invasive procedures, or number of doses of sucrose that might have had an effect on the NAPI scores. So few infants received sedatives (4) or analgesics (3) that these medications were not able to be included in the analysis. After analyses of Pearson correlation coefficients, which fell below 0.5, thus satisfying lack of multicollinearity, the predictor variables for the 2 sets of standard regression analyses (ie, a set for sucrose group and a set for water group) on each NAPI outcome, were 1) age at birth, 2) CRIB, 3) days on caffeine, 4) days on indomethacin, 5) number of painful procedures, and 6) number of doses of sucrose or water. At 32 weeks, there were no significant predictive factors on the NAPI. Significant predictors were identified for only the sucrose group, with no factors reaching significance in the water group (Table 2). At 36 weeks, more developed MDV and more developed AO were predicted for the sucrose group by fewer days on indomethacin and fewer doses of sucrose. At 40 weeks, fewer doses of sucrose predicted more developed MDV and fewer days on indomethacin predicted more AO (Table 2). The only site differences were accounted for by days on indomethacin.
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SNAP and NBRS
There were no group differences or factors associated with SNAP over each day, with day 7 being of interest because it was calculated on the final 24 hours of the intervention and would be most reflective of cumulative physiologic effects of the intervention (sucrose = 3.72 [3.33], water = 4.10 [3.18]; F(1,101) = 0.093, P = .761). On the basis of analysis of covariance with PCA at birth and number of invasive procedures as covariates, there were no group differences on any of the secondary outcomes of NBRS scores at 2 weeks’ postnatal age (sucrose = 1.42 [1.32], water = 1.68 [1.58]; F(1,101) = 0.640, P = .426) or at discharge (sucrose = 2.29 [2.68], water = 2.31 [2.47]; F(1,100) = 0.002, P = .965).
In the regression analysis to determine background and clinical factors that might have predicted higher (worse) physiologically based illness scores, multiple factors were identified (Table 3). Younger age was predictive of higher SNAP scores on study day 7 for the water group only. At 2 weeks’ postnatal age, younger PCA, fewer days on caffeine, and greater number of invasive procedures were predictive of higher NBRS for the water group, and fewer days on caffeine and greater number of doses of sucrose were predictive of higher NBRS for the sucrose group. For the NBRS at discharge, younger age, fewer days on caffeine, and greater number of invasive procedures were predictive of higher NBRS for the water group. However, fewer days on caffeine was predictive of higher NBRS at discharge for the sucrose group.
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DISCUSSION |
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There were no differences on either neurobehavioral developmental outcomes or severity of illness outcomes between infants who received sucrose for painful procedures in the first week of life and those who received water. Because compliance was often low, number of doses of study solution that the infants received was examined for influencing outcomes.
Surprisingly, the effect of number of doses of sucrose was related in the opposite direction than predicted on the neurobehavioral outcomes at 2 of the 3 test ages and on 1 severity of illness outcome before discharge. The number of doses was significant only in the sucrose group. Because the number of study solution doses was not different between the sucrose and water groups, the effect of the procedure to administer a solution in the infant’s mouth in association with a painful procedure can be dismissed.
Tolerance to the sucrose was considered as a possible explanation for the relationship between total doses of sucrose and the outcomes. In this study, the few infants for whom facial expressions of pain could be coded showed a decrease in facial actions for those in the sucrose group compared with those in the water group late in the intervention (days 6–7), as well as in the initial period of the intervention, so sucrose seemed to be analgesic even after several days of receiving it. Thus, sucrose seemed to remain effective in decreasing pain during the study period and there were no signs of tolerance to its analgesic effect. A methodological explanation is that the sample size was inadequate. Sample size was calculated on univariate analyses for each outcome. Thus, when some factors appear as significant for some outcomes but not for others, this could be a result of a sample size that was inadequate in terms of the relative colinearity of the variables of interest. There may be other factors that did not seem to be significant because the sample size was inadequate to detect them.
Nevertheless, the results of this study should not be ignored. The number of doses of sucrose, as opposed to water, was related to several outcome variables in a way that suggests that for infants <32 weeks’ PCA, receiving more doses of sucrose during the first week of life may have questionable long-term effects, despite immediate beneficial effects. The underlying mechanism for sucrose analgesia is understood to be attributable to the release of endogenous opiates as a result of sweet taste.1, 2, 33 By giving the sucrose analgesia for 1 week only and then withdrawing it, we may have increased the sensitivity to subsequent pain. This is based on an animal study in which it was found that exposure to morphine at birth resulted in increased morphine threshold in adulthood.34 Related to this possibility is that the infants may have failed to adopt appropriate self-modulating behaviors, relying instead on external mediators (sucrose). When this external mediating resource was removed, they were slower in developing self-modulating behaviors, which resulted in neurobehavioral and physiologic consequences in the subsequent few weeks. The outcome measures, with the exception of the SNAP on day 7, were at least 1 week beyond the cessation of the intervention, so they may have had heightened pain experience in the intervening time.
Although there is not a clear age delineation, there are indications from animal models that the endogenous opiate system does not become functional until the third trimester or 32 weeks’ PCA.35 The infants in this study were born at <31 weeks’ PCA and received sucrose analgesia (or water) at <32 weeks 2 days. Although we and others have shown an analgesic effect of sucrose in infants <32 weeks for a single painful event,36–39 other studies on preterm infants were with infants 32 weeks or older. 40, 41 Perhaps in infants <32 weeks’ PCA, the repeated stimulation of an immature endogenous opiate system by routine use of sucrose "stresses" the system or interferes with the normal developmental functioning and maturation of this system. For example, a possible explanation for the negative neurobehavioral outcomes could be cross-sensitization between dopamine and endogenous opiates. It is possible that chronic opioid release (as activated by routine sucrose administration) would repeatedly stimulate dopaminergic neurons that are implicated in locomotor activity and arousal.42–45 The projecting areas of these neurons may not be mature enough to demonstrate motor sensitization and in fact could even be inhibitory at this age. This may then explain the higher alertness scores as well as higher motor development scores being predicted by fewer sucrose doses.
The first week of life was selected for this study because that is typically the time of the highest number of invasive procedures14, 15 and, as well, the younger the infant, the greater the number of interventions because the infant requires more external support for stabilization.46 Replication of this study is strongly urged but with a larger sample or a less varied sample, with assurance of greater compliance, and inclusion of ongoing physiologic data for all infants. We did have physiologic data on some infants, but there were no group differences and there were too few infants with complete physiologic monitoring to conduct the same regression analyses as in this report.
Other significant results have not been reported. Although Grunau et al17 reported that dexamethasone exposure may have detrimental long-term outcomes despite its immediate benefit, this was not found for indomethacin. The administration of caffeine seems to be associated with long-term beneficial effects in this study. This has not been reported previously, although a Cochrane review on caffeine for the treatment of apnea of prematurity suggested that it is the preferred treatment for apnea of prematurity and recommended additional study on later effects.47
Although it could be argued that the clinical magnitude of our findings were not worrisome, we cannot recommend that sucrose analgesia be used routinely for every painful event in infants <32 weeks’ PCA despite much evidence of its immediate beneficial effect. It could be that older infants, >32 weeks, would benefit from the routine use of sucrose analgesia or that it should be continued beyond 1 week. Because of the recent recommendation of the use of sucrose routinely13 and the increasing numbers of NICUs that are recommending its use routinely, it is particularly important that selection criteria for the appropriate population be established.
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ACKNOWLEDGMENTS |
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Funding for this study came from the Fonds de la Recherche en Sante du Quebec (961297-104), the IWK Foundation, and Health Canada (career award to C.C.J.; 6605-4286-48).
We thank the families who participated in the study, as well as the staffs in the participating NICUs.
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FOOTNOTES |
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Received for publication Jul 6, 2001; Accepted Mar 5, 2002.
Reprint requests to (C.C.J.) McGill University School of Nursing, 3506 University St, Montreal, QC, Canada, H3A 2A7. E-mail: celeste.johnston{at}mcgill.ca
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REFERENCES |
|---|
|
TOPABSTRACTINTRODUCTIONMETHODSRESULTSDISCUSSIONREFERENCES |
|---|
- Barr RG, Young SN. A two phase model of soothing taste response: implications for a taste probe of temperament and emotion regulation. In: Lewis M, Ramsay DS, eds. Soothing and Stress. Hillsdale, NJ: Lawrence Erlbaum Associates; 1999:109–137
- Blass EM, Ciaramitaro V. A new look at some old mechanisms in human newborns: taste and tactile determinants of state, affect, and action. Monogr Soc Res Child Dev.1994; 59 :1 –80
- Blass EM, Shah A. Pain reducing properties of sucrose in human newborns [abstract].
Chem Senses.1995; 20
:29
–35
[Abstract/Free Full Text] - Blass EM, Watt LB. Suckling- and sucrose-induced analgesia in human newborns. Pain.1999; 83 :611 –623[CrossRef][Web of Science][Medline]
- Stevens BJ, Ohlsson A. The efficacy of sucrose to reduce procedural pain (from heel lance, venepuncture or immunization) in neonates as assessed by physiologic and/or behavioral outcomes. In: Sinclair JC, ed. Neonatal Modules of the Cochrane Data Base of Systematic Reviews. Oxford: The Cochrane Collaboration; 1999
- Ramenghi LA, Evans DJ, Levene MI. "Sucrose analgesia": absorptive mechanism or taste perception?
Arch Dis Child Fetal Neonatal Ed.1999; 80
:F146
–F147
[Abstract/Free Full Text] - Graillon A, Barr RG, Young SN, Wright JH, Hendricks LA. Differential response to intraoral sucrose, quinine and corn oil in crying human newborns. Physiol Behav.1997; 62 :317 –325[CrossRef][Medline]
- Blass EM, Shide DJ. Some comparisons among the calming and pain relieving effects of sucrose, glucose, fructose, and lactose in infant rats.
Chem Senses.1994; 19
:239
–249
[Abstract/Free Full Text] - Carbajal R, Chauvet X, Couderc S, Olivier-Martin M. Randomised trial of analgesic effects of sucrose, glucose, and pacifiers in term neonates.
BMJ.1999; 319
:1393
–1397
[Abstract/Free Full Text] - Eriksson M, Gradin M, Schollin J. Oral glucose and venepuncture reduce blood sampling pain in newborns. Early Hum Dev.1999; 55 :211 –218[CrossRef][Web of Science][Medline]
- Blass EM. Milk-induced hypoalgesia in human newborns.
Pediatrics.1997; 99
:825
–829
[Abstract/Free Full Text] - Ors R, Ozek E, Baysoy G, et al. Comparison of sucrose and human milk on pain response in newborns. Eur J Pediatr.1999; 158 :63 –66[CrossRef][Web of Science][Medline]
- American Academy of Pediatrics. Committee on Fetus and Newborn. Committee on Drugs. Section on Anesthesiology. Section on Surgery. Canadian Paediatric Society. Fetus and Newborn Committee. Prevention and management of pain and stress in the neonate.
Pediatrics.2000; 105
:454
–461
[Abstract/Free Full Text] - Anand KJ, Selankio JD. SOPAIN Study Group. Routine analgesia practices in 109 neonatal intensive care units (NICU’s) [abstract]. Pediatr Res.1996; 39 :192A
- Johnston CC, Collinge JM, Henderson S, Anand KJS. A cross sectional survey of pain and analgesia in Canadian neonatal intensive care units. Clin J Pain.1997; 13 :1 –5[CrossRef][Web of Science][Medline]
- Barker DP, Rutter N. Exposure to invasive procedures in neonatal intensive care unit admissions.
Arch Dis Child Fetal Neonatal Ed.1995; 72
:F47
–F48
[Abstract/Free Full Text] - Grunau RE, Oberlander TF, Whitfield MF, Fitzgerald C, Lee SK. Demographic and therapeutic determinants of pain reactivity in very low birth weight neonates at 32 weeks’ postconceptional age.
Pediatrics.2001; 107
:105
–112
[Abstract/Free Full Text] - Johnston CC, Stevens BJ. Experience in a neonatal intensive care unit affects pain response.
Pediatrics.1996; 98
:925
–930
[Abstract/Free Full Text] - Korner AF, Thom VA. Neurobehavioral Assessment of the Preterm Infant: Manual. San Diego, CA: The Psychological Corporation. Harcourt, Brace, Jovanovich, Inc; 1990:1–83
- Grunau RVE, Craig KD. Facial activity as a measure of neonatal pain expression. In: Tyler DC, Krane EJ, eds. Advances in Pain Therapy and Research. Vol 15: Pediatric Pain. New York: Raven Press; 1990:147–156
- Johnston C, Stevens BJ, Yang F, Horton L. Differential response to pain by very premature neonates. Pain.1995; 61 :471 –479[CrossRef][Web of Science][Medline]
- Korner AF, Kraemer HC, Reade EP, Forrest T, Dimiceli S, Thom VA. A methodological approach to developing an assessment procedure for testing the neurobehavioral maturity of preterm infants. Child Dev.1987; 58 :1478 –1487[CrossRef][Web of Science][Medline]
- Korner AF, Constantinou J, Dimiceli S, Brown BW, Thom VA. Establishing the reliability and developmental validity of a neurobehavioral assessment for preterm infants: a methodological process. Child Dev.1991; 62 :1200 –1208[CrossRef][Web of Science][Medline]
- Korner AF, Brown BW Jr, Dimiceli S, et al. Stable individual differences in developmentally changing preterm infants: a replicated study. Child Dev.1989; 60 :502 –513[CrossRef][Web of Science][Medline]
- Korner AF, Stevenson DK, Kraemer HC, et al. Prediction of the development of low birth weight preterm infants by a new neonatal medical index. Dev Behav Pediatr.1993; 14 :106 –111[Web of Science][Medline]
- Korner AF, Stevenson DK, Forrest T, Constantinou JC, Dimiceli S, Brown BW. Preterm medical complications differentially affect neurobehavioral functions: results from a new neonatal medical index. Infant Behav Dev.1994; 17 :37 –43
- Richardson DK, Escobar GJ. Simplified and revalidated score for neonatal acute physiology (SNAP-II) maintains excellent predictive performance. Pediatr Res.1998; 43 :227A
- Richardson DK, Gray JE, McCormick MC, Workman K, Goldmann DA. Score for neonatal acute physiology: a physiologic severity index for neonatal intensive care.
Pediatrics.1993; 91
:617
–623
[Abstract/Free Full Text] - Brazy JE, Eckerman CO, Oehler JM, Goldstein RF, O’Rand AM. Nursery neurobiologic risk score: important factors in predicting outcome in very low birth weight infants. J Pediatr.1991; 118 :783 –792[CrossRef][Web of Science][Medline]
- The International Neonatal Network. The CRIB (clinical risk index for babies) score: a tool for assessing initial neonatal risk and comparing performance of neonatal intensive care units. Lancet.1993; 342 :193 –198[CrossRef][Web of Science][Medline]
- Hope P. CRIB, son of Apgar, brother to APACHE. Arch Dis Child.1995; 72 :F81 –F83
- Bard H. Assessing neonatal risk: CRIB vs SNAP. Lancet.1993; 342 :449 –450[CrossRef][Web of Science][Medline]
- Gibbins S, Stevens B. Mechanisms of sucrose and non-nutritive sucking in procedural pain management in infants. Pain Res Manag.2001; 6 :21 –28[Medline]
- Rahman W, Fitzgerald M, Aynsley-Green A, Dickenson AH. The effects of neonatal exposure to inflammation and/or morphine on neuronal responses and morphine analgesia in adult rats. In: Jensen TS, Turner JA, Wiesenfeld-Hallin Z, eds. Proceedings of the 8th World Congress on Pain. Seattle, WA: IASP Press; 1997:783–794
- Fitzgerald M. Development of the peripheral and spinal pain system. In: Anand KJS, Stevens BJ, McGrath PJ, eds. Pain in Neonates. Amsterdam, the Netherlands: Elsevier; 2000:9–21
- Bucher HU, Moser T, Von Siebenthal K, Keel M, Wolf M, Duc G. Sucrose reduces pain reaction to heel lancing in preterm infants: a placebo controlled randomized and masked study. Pediatr Res.1995; 38 :332 –335[Web of Science][Medline]
- Stevens BJ, Johnston C, Franck L, Petryshen P, Jack A, Foster R. The efficacy of developmentally sensitive interventions and sucrose for relieving procedural pain in very low birth weight neonates. Nurs Res.1999; 98 :35 –43
- Johnston CC, Stremler RL, Stevens BJ, Horton LJ. Effectiveness of oral sucrose and simulated rocking on pain response in preterm neonates. Pain.1997; 72 :193 –199[CrossRef][Web of Science][Medline]
- Johnston CC, Stremler RL, Horton L, Freidman A. Repeated doses of oral sucrose for decreasing pain from heelstick in preterm neonates. Biol Neonate.1999; 75 :160 –166[CrossRef][Web of Science][Medline]
- Abad F, Diaz NM, Domenech E, Robayna M, Rico J. Oral sweet solution reduces pain-related behaviour in preterm infants. Acta Paediatr.1996; 85 :854 –858[Web of Science][Medline]
- Ramenghi LA, Wood CM, Griffith GC, Levene MI. Reduction of pain response in premature infants using intraoral sucrose.
Arch Dis Child Fetal Neonatal Ed.1996; 74
:F126
–F128
[Abstract/Free Full Text] - Altier N, Stewart J. The role of dopamine in the nucleus accumbens in analgesia [review]. Life Sci.1999; 65 :2269 –2287[CrossRef][Web of Science][Medline]
- Altier N, Stewart J. Intra-VTA infusions of the substance P analogue, DiMe-C7, and intra-accumbens infusions of amphetamine induce analgesia in the formalin test for tonic pain. Brain Res.1993; 628 :279 –285[CrossRef][Web of Science][Medline]
- Altier N, Stewart J. Dopamine receptor antagonists in the nucleus accumbens attenuate analgesia induced by ventral tegmental area substance P or morphine and by nucleus accumbens amphetamine.
J Pharmacol Exp Ther.1998; 285
:208
–215
[Abstract/Free Full Text] - Altier N, Stewart J. Opioid receptors in the ventral tegmental area contribute to stress-induced analgesia in the formalin test for tonic pain. Brain Res.1996; 718 :203 –206[CrossRef][Web of Science][Medline]
- Gray JE, Richardson DK, McCormick MC, Workman-Daniels K, Goldmann DA. Neonatal therapeutic intervention scoring system: a therapy based severity of illness index.
Pediatrics.1992; 90
:561
–567
[Abstract/Free Full Text] - Steer PA, Henderson-Smart DJ. Caffeine versus theophylline for apnea in preterm infants. Cochrane Database Syst Rev.2000; CD000273
PEDIATRICS (ISSN 1098-4275). ©2002 by the American Academy of Pediatrics
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