Procedural Pain In Preterm Infants Research Articles

Factors influencing nurses' practice of skin-to-skin contact as a pain management intervention for preterm infants

PurposeTo identify contextual as well as individual (personal and professional) factors influencing the practice of skin-to-skin contact (SSC) by nurses as a pain management intervention for preterm infants. SSC is among the most effective non-pharmacological interventions to manage procedural pain in preterm infants. MethodsIn this secondary analysis of a comparative international cross-sectional design study, 202 nurses were recruited and completed self-administered questionnaires. A mixed model was conducted. ResultsThe contextual factors correlated with the use of SSC for pain management included the country (p < 0.001) and work shift (p < 0.001). Individual nurse factors were level of education (p < 0.001), motherhood history (p < 0.001) as well as self-reported skin-to-skin practices [p < 0.001] (positive attitudes, education, and implementation). ConclusionMany factors may contribute to explain the differences in the use of SSC for pain management by nurses. These factors could be of relevant to consider when implanting SSC to manage procedural pain in preterm neonates.

The effect of music on pain management in preterm infants during daily painful procedures: a systematic review and meta-analysis.

The present systematic review and meta-analysis of randomized controlled trials (RCTs) was conducted to investigate the effects of music on pain management in preterm neonates during painful procedures. The PubMed, Embase, Web of Science, EBSCO and Cochrane Library databases were searched to identify relevant articles published from their inception to September 2023. The study search strategy and all other processes were implemented in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. Four RCTs that satisfied the inclusion criteria were included in this meta-analysis. The music group had significantly lower Premature Infant Pain Profile (PIPP) scores during (RR = -1.21; 95% CI = -2.02--0.40, p = 0.0032) and after painful procedures (RR = -0.65; 95% CI = -1.06--0.23, p = 0.002). The music group showed fewer changes in PIPP scores after invasive operations than did the control group (RR = -2.06; 95% CI -3.16--0.96; p = 0.0002). Moreover, our results showed that music improved oxygen saturation during (RR = 3.04, 95% CI = 1.64-4.44, p < 0.0001) and after painful procedures (RR = 3.50, 95% CI = 2.11-4.90, p < 0.00001). However, the change in peak heart rate during and after painful procedures was not statistically significant (RR = -12.14; 95% CI = -29.70-5.41 p = 0.18; RR = -10.41; 95% CI = -22.72-1.90 p = 0.10). In conclusion, this systematic review demonstrated that music interventions are effective for relieving procedural pain in preterm infants. Our results indicate that music can reduce stress levels and improve blood oxygen saturation. Due to the current limitations, large-scale, prospective RCTs should be performed to validate the present results.

Cerebral hemodynamic response to a therapeutic bed for procedural pain management in preterm infants in the NICU: a randomized controlled trial.

We developed a novel device, Calmer, that mimics key components of skin-to-skin holding to reduce stress in preterm infants. Our feasibility trial showed that Calmer worked 50% better than no treatment and no differently from our standard of care, facilitated tucking (FT), for reducing pain scores during a heel lance in preterm infants in the neonatal intensive care unit. We compared the effects of Calmer on regional cerebral hemodynamic activity during a noxious stimulation to FT. During a clinically required heel lance, we measured frontal cortex tissue oxygenation in a subsample of 29 preterm infants (27-33 weeks gestational age) from our larger randomized controlled trial. Infants were randomized to either FT (n = 16) or Calmer treatment (n = 12). The outcome measure, obtained using near-infrared spectroscopy, was a change in the tissue oxygenation index (TSI) across study phases (Baseline, Heel Lance, Recovery; median duration 517 seconds [421-906 seconds]). No statistically significant differences were found between groups in the median TSI during any of the study phases. In response to the heel lance, 7 infants (27.6%) had a TSI that dipped below the 60% threshold (3 in the Calmer group 25% and 4 in the FT group 25%); none below 50%. Infants on Calmer maintained normal regional cerebral oxygen levels (55%-85%) no differently from infants receiving a human touch intervention during blood collection. Parental skin-to-skin holding is one of the most effective strategies to relieve procedural pain in preterm infants. When parents or FT are not available, Calmer shows potential for filling this gap in care.

The effect of early procedural pain in preterm infants on the maturation of electroencephalogram and heart rate variability.

Preterm infants show a higher incidence of cognitive, social, and behavioral problems, even in the absence of major medical complications during their stay in the neonatal intensive care unit (NICU). Several authors suggest that early-life experience of stress and procedural pain could impact cerebral development and maturation resulting in an altered development of cognition, behavior, or motor patterns in later life. However, it remains very difficult to assess this impact of procedural pain on physiological development. This study describes the maturation of electroencephalogram (EEG) signals and heart rate variability in a prospective cohort of 92 preterm infants (<34 weeks gestational age) during their NICU stay. We took into account the number of noxious, ie, skin-breaking, procedures they were subjected in the first 5 days of life, which corresponded to a median age of 31 weeks and 4 days. Using physiological signal modelling, this study shows that a high exposure to early procedural pain, measured as skin-breaking procedures, increased the level of discontinuity in both EEG and heart rate variability in preterm infants. These findings have also been confirmed in a subset of the most vulnerable preterm infants with a gestational age lower than 29 weeks. We conclude that a high level of early pain exposure in the NICU increases the level of functional dysmaturity, which can ultimately impact preterm infants' future developmental outcome.

The newborn infant parasympathetic evaluation index for acute procedural pain assessment in preterm infants.

Accurate assessments of pain in hospitalized preterm infants present a major challenge in improving the short- and long-term consequences associated with painful experiences. We evaluated the ability of the newborn infant parasympathetic evaluation (NIPE) index to detect acute procedural pain in preterm infants. Different painful and stressful interventions were prospectively observed in preterm infants born at 25 + 0 to 35 + 6 weeks gestation. Pain responses were measured using the composite Premature Infant Pain Profile Revised (PIPP-R) scale, the NIPE index, and skin conductance responses (SCR). Outcome measures were correlations between the NIPE index, the PIPP-R score, and the SCR. Sensitivity/specificity analyses tested the accuracy of the NIPE index and SCR. Two hundred and fifty-four procedures were recorded in 90 preterm infants. No significant correlation was found between PIPP-R and the NIPE index. PIPP-R and SCR were positively correlated (r = 0.27, P < 0.001), with stronger correlations for painful procedures (r = 0.68, P < 0.001) and especially for skin-breaking procedures (r = 0.82, P < 0.001). The NIPE index and SCR had high sensitivity and high negative predictive values to predict PIPP-R > 10, especially for skin-breaking painful procedures. We found no significant correlation between the NIPE index and PIPP-R during routine painful or stressful procedures in preterm infants. Exposure to repetitive pain can lead to neurodevelopmental sequelae. Behavior-based pain scales have limited clinical utility, especially for preterm infants. New devices for monitoring physiological responses to pain have not been validated sufficiently in preterm infants. This study found that the NIPE index was not significantly correlated to the validated PIPP-R scale during acute procedural pain. Secondary analysis of this study showed that NIPE index and SCRs may help to exclude severe pain in preterm infants. In clinical practice, measurements of physiological parameters should be combined with behavior-based scales for multidimensional pain assessments.

Management of procedural pain in preterm infants through olfactive stimulation with mothers’ milk: A pilot study

Introduction: Repeated and untreated pain can lead to long-term consequences in preterm infants, such as pain hypersensitivity and impaired motor and intellectual development. Studies on pharmacological and non-pharmacological interventions for pain management in preterm infants are limited. Thus, we piloted an intervention based on olfactive stimulation with mothers’ milk. Objective: To assess the feasibility, acceptability, and preliminary effects of an olfactive stimulation intervention with mothers’ milk for procedural pain in preterm infants. Methods: A pilot study was conducted with mothers, nurses, and preterm infants. Twelve preterm infants were familiarized to the odor of their mother’s milk 9 hours before heel prick. During heel prick, mothers’ milk odor was combined with standard care by placing a pad saturated with mothers’ milk beneath the infant’s nose. Pain was measured using Preterm Infant Pain Profile-Revised tool. Mothers (n=11) and nurses (n=20) completed questionnaires regarding feasibility and acceptability. Results: More than 80% of mothers and nurses reported that the olfactive stimulation intervention was feasible and acceptable. Time taken for preterm infants’ heart rate and oxygen saturation to return to the baseline was reduced and pain scores were lower when the mothers’ milk pad was placed at 1 millimeter(mm) of the infant’s nose. Discussion and conclusion: The olfactive stimulation intervention is feasible and acceptable for nurses and mothers. The observed preliminary effects suggest that a pad saturated in mother’s milk placed 1 mm from the preterm infants’ nose could reduce the pain response. A randomized clinical trial should be conducted to assess the effectiveness of this intervention.

Effect of non-nutritive sucking and sucrose alone and in combination for repeated procedural pain in preterm infants: A randomized controlled trial

BackgroundSucrose combined with non-nutritive sucking provided better pain relief than sucrose or non-nutritive sucking alone in a single painful procedure. However, whether the combination of non-nutritive sucking with sucrose could obtain a significant difference in analgesic effect of the repeated procedural pain than any single intervention has not been established. ObjectiveTo compare the effect of non-nutritive sucking and sucrose alone and in combination of repeated procedural pain in preterm infants. DesignRandomized controlled trial. SettingA level III neonatal intensive care unit of a university hospital in China. MethodPreterm infants born before 37 weeks of gestation were randomly assigned to four groups: routine care group (routine comfort through gentle touch when infants cried; n = 21), non-nutritive sucking group (n = 22), sucrose group (0.2 ml/kg of 20%; n = 21), sucrose (0.2 ml/kg of 20%) plus non-nutritive sucking group (n = 22). Each preterm infant received three nonconsecutive routine heel sticks. Each heel stick included three phases: baseline (the last 1 min of the 30 min without stimuli), blood collection, recovery (1 min after blood collection). Three phases of 3 heel stick procedures were videotaped. Premature infant pain profile (PIPP) score, heart rate, oxygen saturation and percentage of crying time were assessed by five independent evaluators who were blinded to the purpose of the study at different phases across three heel sticks. Data were analyzed by analysis of variance, with repeated measures at different evaluation phases of heel stick. Results86 preterm infants completed the protocol. During the blood collection and recovery phases, combination group, had lower PIPP score (4.4 ± 1.5; 3.0 ± 0.8), lower heart rate (138.6 ± 7.9; 137.4 ± 4.7), higher oxygen saturation (95.2 ± 1.6; 96.0 ± 1.2), and smaller percentage of crying time (11.5 ± 8.6; 4.6 ± 3.4), compared with the group has given non-nutritive sucking (9.3 ± 1.3, 6.8 ± 1.4; 154.2 ± 9.0, 148.0 ± 9.3; 92.9 ± 2.4, 94.1 ± 1.0; 44.2 ± 9.6, 31.2 ± 10.5; respectively) or sucrose (10.1 ± 2.0, 7.4 ± 1.6; 151.6 ± 9.6, 147.9 ± 6.9; 93.5 ± 1.7, 94.5 ± 1.2; 53.8 ± 16.7, 35.2 ± 13.9; respectively) or routine care (13.3 ± 1.6, 10.6 ± 1.9; 156.8 ± 7.2, 151.7 ± 7.9; 92.9 ± 2.1, 93.8 ± 1.6; 80.6 ± 7.6, 68.2 ± 9.9; respectively). Both non-nutritive sucking and sucrose were more effective in reducing preterm infants’ PIPP score and percentage of crying time than routine care. There was no difference in PIPP score, heart rate, oxygen saturation and percentage of crying time between the non-nutritive sucking and sucrose groups. ConclusionThe combination of non-nutritive sucking with sucrose provided better pain relief during repeated painful procedures than when non-nutritive sucking or sucrose was used alone. The effect of non-nutritive sucking was similar to that of sucrose on repeated procedural pain.

Randomized Controlled Trial Comparing Different Single Doses of Intravenous Paracetamol for Placement of Peripherally Inserted Central Catheters in Preterm Infants

Background: The availability of a safe and effective pharmacological therapy to reduce procedural pain in preterm infants is limited. The effective analgesic single dose of intravenous paracetamol in preterm infants is unknown. Comparative studies on efficacy of different paracetamol doses in preterm infants are lacking. Objectives: To determine the analgesic effects of different single intravenous paracetamol doses on pain from peripherally inserted central catheter (PICC) placement in preterm infants. Methods: In a blinded randomized controlled trial, the analgesic effects of 10-, 15-, and 20-mg/kg single-dose intravenous paracetamol before PICC placement were compared in neonates with a gestational age <32 weeks. Secondly, a separate age-matched nonrandomized control group receiving oral sucrose was included. Pain was assessed with the Premature Infant Pain Profile (PIPP) and the COMFORTneo score. Peak plasma concentrations of paracetamol were determined. Results: A total of 60 patients were included in the paracetamol dose groups (median gestational age = 27.8, IQR: 25.7-29.2 weeks). PIPP scores were comparable: median = 8 (IQR: 6-10.5), 7 (IQR: 6-9), and 8 (IQR: 6-10) for the 10-, 15-, and 20-mg/kg paracetamol groups, respectively (p = 0.94). COMFORTneo scores were not statistically different between the different paracetamol dose groups (p = 0.35). All randomized subjects, except for 3 who received 10 mg/kg of paracetamol, had peak paracetamol concentrations >9 mg/L. PIPP (p = 0.78) and COMFORTneo (p = 0.08) scores were also comparable between paracetamol- and sucrose-treated patients. Conclusions: We found no analgesic benefit from intravenous paracetamol studied in different single doses over sucrose for PICC placement in preterm infants. Paracetamol is not a suitable analgesic for this procedure in preterm infants.

A feasibility and efficacy randomised controlled trial of swaddling for controlling procedural pain in preterm infants.

This study aimed to investigate the feasibility and efficacy of swaddling to control procedural pain among preterm infants. Swaddling has been recommended for controlling neonatal pain. However, the feasibility for use is uncertain and insufficient evidence is available among preterm infants. A two-arm randomised controlled trial with repeated measures. The study was conducted in a 21-bed neonatal intensive care unit of a regional hospital in Hong Kong. Preterm infants who required heelstick procedure were eligible. Fifty-four preterm infants between 30-37 gestational weeks were randomly assigned to swaddling (n=27) and control (standard care, n=27) groups. Pain assessment was performed pre, during, immediate, two, four, six and eight minutes after heelstick procedure using the Premature Infant Pain Profile. The mean Premature Infant Pain Profile scores were significantly reduced in the intervention group compared to the control group during, immediate, two, four, and six minutes after the heelstick procedure. The mean changes of heart rate and oxygen saturation in the intervention group were significantly lower than that of the control group at all measured time points. Notably, the swaddled infants quickly resumed to the baseline level at two minutes whereas the control group reached the stable state at an extended period of six minutes. The findings show that swaddling is feasible and efficacious in controlling pain for heelstick procedure among preterm infants. No adverse effects were observed. This article presents the feasibility and efficacy of swaddling as a non-pharmacological and non-invasive intervention to relieve pain during the heelstick procedures among preterm infants. Swaddling can contribute to control minor procedural pain in neonates as one of the simple, safe, cost effective, humanistic and natural analgesia alternatives.

Effect of repeated Kangaroo Mother Care on repeated procedural pain in preterm infants: A randomized controlled trial.

Preterm infants' repeated exposure to painful procedures may lead to negative consequences. Thus, non-pharmacological pain management is essential due to medication side effects. Kangaroo Mother Care, which aims at offering human care to neonates, has been established for the treatment of a single painful procedure, but the effectiveness of Kangaroo Mother Care across repeated painful procedures is unknown. To test the effectiveness of repeated Kangaroo Mother Care on repeated heel-stick pain in preterm neonates. Randomized controlled trial. Level III Neonatal Intensive Care Unit at a large teaching hospital in northeast China. Preterm infants (gestational age less than 37 weeks) (n=80) were recruited and randomly assigned using a random table format to either an incubator group (n=40) or Kangaroo Mother Care group (n=40). Pain assessments were carried out during four routine heel stick procedures. For the first heel stick, preterm infants in each group received no intervention (routinely stayed in incubator). During the next three heel sticks, the infants in Kangaroo Mother Care group received heel sticks during Kangaroo Mother Care, while infants in the incubator group received heel sticks in incubator. The procedure of each heel stick included 3 phases: baseline, blood collection and recovery. Crying, grimacing and heart rate in response to pain were evaluated at each phase across four heel sticks by three trained independent observers who were blinded to the purpose of the study. Data were analyzed by analysis of variance (ANOVA), with repeated measures at different evaluation phases of heel stick. 75 preterm infants completed the protocol. Between-group comparison revealed that preterm infants' heart rate was significantly lower, and the duration of crying and facial grimacing were both significantly shorter in the Kangaroo Mother Care group (n=38) than the incubator group (n=37) from the blood collection phase to recovery phase during repeated heel sticks. No significant within-group difference was found in heart rate between the baseline phase and recovery phase through repeated heel sticks for Kangaroo Mother Care group. In contrast, the incubator group experienced significant within group differences in heart rate between baseline and recovery through repeated heel sticks. The effect of repeated Kangaroo Mother Care analgesia remains stable in preterm infants over repeated painful procedures. Given the many invasive procedures that are part of clinical care in preterm infants and most mothers preferred to provide comfort for their infants during painful procedures, Kangaroo Mother Care may be a safe analgesic alternative in preterm infants in whom it is feasible.

Trial of Repeated Analgesia with Kangaroo Mother Care (TRAKC Trial)

BackgroundSkin-to-skin contact (SSC) between mother and infant, commonly referred to as Kangaroo Mother Care (KMC), is recommended as an intervention for procedural pain. Evidence demonstrates its consistent efficacy in reducing pain for a single painful procedure. The purpose of this study is to examine the sustained efficacy of KMC, provided during all routine painful procedures for the duration of Neonatal Intensive Care Unit (NICU) hospitalization, in diminishing behavioral pain response in preterm neonates. The efficacy of KMC alone will be compared to standard care of 24% oral sucrose, as well as the combination of KMC and 24% oral sucrose.Methods/designInfants admitted to the NICU who are less than 36 6/7 weeks gestational age (according to early ultrasound), that are stable enough to be held in KMC, will be considered eligible (N = 258). Using a single-blinded randomized parallel group design, participants will be assigned to one of three possible interventions: 1) KMC, 2) combined KMC and sucrose, and 3) sucrose alone, when they undergo any routine painful procedure (heel lance, venipuncture, intravenous, oro/nasogastric insertion). The primary outcome is infant’s pain intensity, which will be assessed using the Premature Infant Pain Profile (PIPP). The secondary outcome will be maturity of neurobehavioral functioning, as measured by the Neurobehavioral Assessment of the Preterm Infant (NAPI). Gestational age, cumulative exposure to KMC provided during non-pain contexts, and maternal cortisol levels will be considered in the analysis. Clinical feasibility will be accounted for from nurse and maternal questionnaires.DiscussionThis will be the first study to examine the repeated use of KMC for managing procedural pain in preterm neonates. It is also the first to compare KMC to sucrose, or the interventions in combination, across time. Based on the theoretical framework of the brain opioid theory of attachment, it is expected that KMC will be a preferred standard of care. However, current pain management guidelines are based on minimal data on repeated use of either intervention. Therefore, regardless of the outcomes of this study, results will have important implications for guidelines and practices related to management of procedural pain in preterm infants.Trial registrationClinicalTrials.gov Identifier: NCT01561547.

Does breastfeeding reduce acute procedural pain in preterm infants in the neonatal intensive care unit? A randomized clinical trial

Managing acute procedural pain effectively in preterm infants in the neonatal intensive care unit remains a significant problem. The objectives of this study were to evaluate the efficacy of breastfeeding for reducing pain and to determine if breastfeeding skills were altered after this treatment. Fifty-seven infants born at 30–36 weeks gestational age were randomized to be breastfed (BF) or to be given a soother during blood collection. Changes in the Behavioral Indicators of Infant Pain (BIIP) and in mean heart rate (HR) across 3 phases of blood collection were measured. In the BF group, the Premature Infant Breastfeeding Behaviors (PIBBS) scale was scored before and 24 hours after blood collection. Longitudinal regression analysis was used to compare changes in Lance/squeeze and Recovery phases of blood collection between groups, with gestational age at birth, baseline BIIP scores, and mean HR included as covariates. Differences in PIBBS scores were assessed using a paired t-test. Relationships between PIBBS scores, BIIP scores, and HR were evaluated with Pearson correlations. No differences between treatment groups were found: BIIP ( P = 0.44, confidence interval [CI] −1.60–0.69); HR ( P = 0.73, CI −7.0–10.0). Infants in the BF group showed improved PIBBS scores after the treatment ( P < 0.01, CI −2.7 to −0.2). Lower BIIP scores during the Lance/squeeze were associated significantly with more mature sucking patterns ( r = −0.39, P < 0.05). Breastfeeding during blood collection did not reduce pain indices or interfere with the acquisition of breastfeeding skills. Exploratory analyses indicate there may be benefit for infants with mature breastfeeding abilities.

Considerations for Using Sucrose to Reduce Procedural Pain in Preterm Infants

Preterm and critically ill newborns admitted to a NICU undergo repeated skin-breaking procedures that are necessary for their survival. Sucrose is rapidly becoming the accepted clinical standard nonpharmacologic intervention for managing acute procedural pain for these infants. Although shown to be safe in single doses, only 4 studies have evaluated the effects of repeated doses of sucrose over relatively short periods of time. None has examined the use of sucrose throughout the NICU stay, and only 1 study evaluated the neurodevelopmental outcomes after repeated doses of sucrose. In that study, infants born at <31 weeks' gestational age and exposed to >10 doses per day in the first week of life were more likely to show poorer attention and motor development in the early months after discharge from the NICU. Results of studies in animal models have suggested that the mechanism of action of sucrose is through opioid pathways; however, in human infants, little has been done to examine the physiologic mechanisms involved, and the findings reported thus far have been ambiguous. Drawing from the growing animal literature of research that has examined the effects of chronic sugar exposure, we describe alternative amine and hormone pathways that are common to the processing of sucrose, attention, and motor development. In addition, a review of the latest research to examine the effects of repeated sucrose on pain processing is presented. These 2 literatures each can inform the other and can provide an impetus to initiate research to examine not only the mechanisms involved in the calming mechanisms of sucrose but also in the long-term neurodevelopmental effects of repeated sucrose in those infants born extremely preterm or critically ill.

Considerations for Using Sucrose to Reduce Procedural Pain in Preterm Infants

Considerations for Using Sucrose to Reduce Procedural Pain in Preterm Infants

Beta-endorphin concentration after administration of sucrose in preterm infants.

Sucrose is an effective analgesic for procedural pain in preterm infants. It has been hypothesized that its analgesic effects are mediated by the release of endogenous opioid neurotransmitters such as beta-endorphin. To determine whether intraoral administration of sucrose was associated with an increase in serum beta-endorphin concentrations in preterm infants with a gestation period less than 29 weeks who were not exposed to a painful stimulus. We performed a prospective open-label study in preterm infants admitted to 2 tertiary neonatal intensive care units. Each infant received a single dose of 30% sucrose intraorally during a 1- to 2-minute period. A blood sample was obtained using an indwelling arterial catheter to determine beta-endorphin concentration immediately before and 2 to 5 minutes after the commencement of sucrose administration. We enrolled 11 preterm infants with a mean +/- SD gestational age of 27.2 +/- 0.9 weeks and a mean +/- SD birth weight of 1018 +/- 238 g (1.02 +/- 0.24 kg) at a mean +/- SD postnatal age of 3.0 +/- 2.5 days. The mean +/- SD beta-endorphin concentration before and after sucrose administration was 60.4 +/- 30.5 pg/mL and 57.4 +/- 22.4 pg/mL, respectively (P =.45). No adverse events were observed during the study procedures. Intraoral administration of sucrose in preterm infants did not lead to an increase in serum beta-endorphin concentrations at a point in time when the analgesic effects of sucrose were presumed to be present.