Music and 25% glucose pain relief for the premature infant: a randomized clinical trial 1

OBJECTIVE: to analyze the total Premature Infant Pain Profile scores of premature infants undergoing arterial puncture during music and 25% glucose interventions, and to assess their association with neonatal and therapeutic variables. METHOD: a randomized clinical trial with 80 premature infants; 24 in the Experimental Group 1 (music), 33 in the Experimental Group 2 (music and 25% glucose), 23 in the Positive Control Group (25% glucose). All premature infants were videotaped and a lullaby was played for ten minutes before puncture in Experimental Groups 1 and 2; 25% glucose administered in Experimental Group 2 and the Positive Control Group two minutes before puncture. RESULTS: 60.0% of premature infants had moderate or maximum pain; pain scores and intervention groups were not statistically significant. Statistically significant variables: Experimental Group 1: head and chest circumference, Apgar scores, corrected gestational age; Experimental Group 2: chest circumference, Apgar scores, oxygen therapy; Positive Control group: birth weight, head circumference. CONCLUSION: neonatal variables are associated with pain in premature infants. Brazilian Registry of Clinical Trials: UTN: U1111-1123-4821.


Introduction
For the sake of survival, newborns, particularly preterm infants (PTI) in the neonatal unit (NU) undergo numerous painful procedures, such as collection of arterial and venous blood, lumbar puncture, venipuncture and tracheal aspiration, among others (1) .
It should be noted that PTI experience pain, but it may vary from that of the term infant because they do not have the ability to produce a strong sound, thereby they may not scream or present with a vocal response that displays a difference between discomfort and severe pain (2) .
Pain can be assessed and analyzed through parameters. Among these, there are behavioral and physiological responses, such as facial movements, crying, sleep and wake patterns, heart rate (HR), blood pressure, respiratory rate (RR), oxygen saturation (SpO 2 ) and systolic blood pressure (3) . Due to the PTI's inability for verbal expression, the development of instruments to assess their pain in preterm infants became necessary.
Among the scales for measurement of acute pain in preterm infants, is the Premature Infant Pain Profile (PIPP) (4) . The use of these instruments may favor the care of the PTI with greater safety and knowledge because it guides important aspects that accompany the reaction of the neonate to painful procedures.
When considering that there are neonatal variables (including sex, gestational age) and interventions (such as upper airway aspiration, venous and arterial punctures), which characterize and continue throughout the newborn's (NB) hospitalization, it is advocated that they can influence the pain reaction. Therefore, its assessment is extremely important in PTI. The use of non-pharmacological measures for pain relief in PTI in the NU, such as 25% glucose (5) and music therapy (6) , are added to those. Therefore, a question arose: what is the relationship between the neonatal and therapeutic variables and PIPP pain scores in PTI under the effect of either music, music associated with 25% glucose, or 25% glucose only? The answers to this question may direct other studies on PTI pain and enable nursing to obtain pain assessment parameters in this clientele through the PIPP and through the use of non-pharmacological measures.
The objective of this study was to analyze total PIPP scores of PTI undergoing arterial puncture for blood collection and exposure to either music, music and 25% glucose, or 25% glucose, and whether there is an association between neonatal variables (gender, type of delivery, birth weight, corrected gestational age (GA), chronological age in days, length of stay in days,

Dimensioning of the PIPP pain scores with neonatal and therapeutic variables
According to Table 1, it was observed that 60.0% of the PTI had moderate or maximum pain. There was no statistically significant association (p=0.398) between the pain score category and the intervention groups.     (8) .
Specifically in relationship to sex, this study corroborates other authors (8) regarding the lack of a statistically significant association for newborns allocated in EG1, EG2 and PCG, although it is shown that newborn males were more reactive to pain in the music group and the 25% glucose group.
Supporting this result in relationship to music, a study that examined the differences in the responses of gender (masculine/feminine) to musical stimuli, subjects were exposed to 21 minutes of lullabies, alternating with three minutes of silence, by means of headphones.
Responses obtained for physiological and behavioral parameters indicated no statistically significant changes for the studied variable; namely, neither the masculine nor feminine gender showed greater receptivity to listening to lullabies, nor did either show a tendency to present higher pain scores (9) .
Compared to the study proposed, when analyzing The females, on the other hand, showed no pain during physical therapy, using the NIPS or the NFCS assessments (10) .  (11) , which resembles the newborns allocated in EG2 and PCG, whose GA did not influence the pain response in PTI.
A comparative quasi-experimental study performed at the Maternity Unit in the interior of São Paulo state evaluated 40 newborns at term during the vaccination procedure against Hepatitis B through the NFCS. The results identified a significant association between groups regarding GA in days (p = 0.02), however, it was not clinically relevant, since the two groups were comprised of term infants. Furthermore, it was identified that the mean birth weight of newborns, 3.190g for those immediately placed in skin to skin contact with the mother after delivery, and 3.325g for those taken directly to the heated crib, showed no association between the groups (p=0.29) (13) . In the present study on the other hand, weight showed a statistically significant difference for the premature in PCG (p=0.045).
Regarding the Apgar investigation, in the experimental group (EG1 and EG2), the PTI was statistically significant for 1' and 5' Apgar, although the mean 5' Apgar score was above seven.
A clinical trial conducted in eastern Canada aimed to evaluate the effect of co-sleeping in recovery and response to pain, using the PIPP with 67 premature twin neonates at GA between 28 and 36 weeks, divided into two groups: those treated in the same incubator Cardoso MVLML, Farias LM, Melo GM.
or crib (co-sleeping) and another group that received care in separate incubators or cribs. Comparing the groups, there was a statistically significant difference on the day of heel lance regarding the 5 'Apgar variable (p=0.05 (14) .
Regarding the evolution of head circumference, another investigation with 63 PTI at GA between 28 and 33 weeks, who heard classical music (Mozart) for 20 minutes on two consecutive days, found no statistically significant difference among hospitalized newborns in the NICU undergoing music therapy and the control group (16) .
Regarding therapeutic variables, a quantitative longitudinal before-and-after study in a NICU in Fortaleza, CE, investigated the physiological parameters of RR, HR, pulse rate (P), SpO 2 , before, immediately after and five minutes after performing tracheal (TA) and upper airway aspiration (UAA) of 104 newborns. Results showed that newborns using an Oxi-Hood suffered the biggest changes in respiratory function, manifested as trouble returning to pre-aspiration RR values , differing from the results of the present study (17) .
An experimental study with 20 PTI undergoing installation and reinstallation of nasal CPAP indicated that when this artifact was installed, 100% of newborns felt pain. However, when they were offered non-nutritive sucking (minimum of a gloved finger in the mouth of the NB), the premature infants reacted to the stimulus without reaching an indicative pain score through NIPS (18) , similar to the EG1 and PCG.

Conclusion
The study design was adequate to the proposed objectives. When analyzing the relationship of neonatal and treatment variables with PTI undergoing arterial puncture for blood collection while exposed to either music, music and 25% glucose, or 25% glucose alone, it was found that the three study groups were heterogeneous in some variables. This is an important aspect because some of these variables showed significant differences regarding pain patterns: 1' Apgar, 5' Apgar, gestational age, weight, HC, CC and type of oxygen therapy with p <0.05.
Among the study's limitations is the inclusion of PTI on oxygen therapy, because they had PIPP scale scores significantly higher than the others, which indicates that such a situation should perhaps have been considered as an exclusion criterion.
The contribution is the encouragement of performing a clinical trial with PTI undergoing arterial puncture under three types of interventions for pain relief: music, music and 25% glucose and 25% glucose, with pain being assessed through the multidimensional PIPP scale, and its relationship with neonatal and therapeutic variables in the NICU.