Dimensioning of painful procedures and interventions for acute pain relief in premature infants 1

ABSTRACT Objective: to dimension the exposure of premature infants to painful procedures, relating the distribution of the exposure to contextual factors, as well as to describe the pharmacological and non-pharmacological interventions health professionals use during the first two weeks of the infant’s hospitalization at two neonatal services. Method: descriptive-exploratory study in which the professionals registered the painful procedures and pain relief interventions on a specific form in the patient file. Results: the daily average of the 89 premature infants was 5.37 painful procedures, corresponding to 6.56 during the first week of hospitalization and 4.18 during the second week (p<0.0001). The most frequent procedures were nasal/oral (35.85%) and tracheal aspirations (17.17%). The children under invasive ventilation were the most exposed to painful procedures (71.2%). Only 44.9% of the painful procedures received some intervention for the purpose of pain relief, the most frequent being sucrose (78.21%) and continuing sedation (19.82%). Conclusion: acute pain was undertreated at these neonatal services, recommending greater sensitization of the team for the effective use of the existing protocol and implementation of other knowledge transfer strategies to improve neonatal pain management.


Introduction
Preterm birth has represented a public health problem, which requires specific interventions to improve this population's quality of life (1) . Preterm infants were born before the 37 th week of pregnancy (1) , classified as extremely preterm (<28 weeks of pregnancy), very preterm (between 28 and <32 weeks of pregnancy) and moderate to late preterm (between 32 and <37 weeks of pregnancy) (1) .
The preterm infant's trajectory starts with the hospitalization, often over long periods, at neonatal services, where they are exposed to many stimuli related to lighting, noise and manipulation (2) .
Among the different types of manipulation the preterm infants are exposed to, the painful procedures stand out, which are necessary for the sake of diagnostic and therapeutic implementation, causing immediate changes in physiological (such as cardiac frequency, respiratory frequency, blood pressure, oxygen saturation and hormone dosage) and behavioral parameters (such as crying, motor activity, facial mimics, state of irritability and agitation) (3) and, in the long term, triggering phenomena such as allodynia and hyperalgesia (4) .
Therefore, the exposure of infants to painful procedures has been investigated in different countries (such as the Netherlands, Australia, Canada and France), using different methodological designs to dimension the exposure of full-term and preterm infants and children to painful procedures during 24 hours (5) , 14 days of hospitalization (6)(7) or 28 days or longer (8) , at a Neonatal Intensive Care Unit (UTIN).
Recently, only one study has been identified in Brazil that dimensioned the pain of infants during seven days at an UTIN (9) . The exposure to painful procedures differs among the studies, ranging between treatment and 14 painful procedures per day (5)(6)(7)(8)(9) .
Specifically preterm infants are more vulnerable to the effects of repeated and prolonged exposure to painful and stressing procedures, which can contribute to neurobehavioral development problems (10) . It is important to study this specific population concerning the exposure to painful procedures and acute pain management by the health professionals at neonatal services.
In addition, contextual factors related to the individual (maturity, health condition and temperament), the environment (diagnostic and therapeutic interventions) and the care team (positioning and manipulation) can influence the pain response (11) .
Strong scientific evidence exists for the use of pharmacological (12) and non-pharmacological interventions, such as sucrose (13) , kangaroo position (14) and breastfeeding (15) , on neonatal pain reduction, but the long-term effects of these interventions remain unknown. and, in order to compare the mean numbers of painful procedures, according to the variables "birth weight" and "gestational age", one-way ANOVA (α = 0.05) was applied; for "sex" and "invasive ventilation", the unpaired Student t test (α = 0.05) and "hospitalization period", Student's t test for two paired samples (α = 0.05).

Results
Of the 89 preterm infants in the study, 46 (51.7%) were males. The mean weight at birth was 1,384. As for painful procedures, the 89 preterm infants were exposed to 6,678 painful procedures, with 12,300 attempts, during the first two weeks of life in the neonatal units, averaging 1.8 ± 1.0 attempts per procedure. Each preterm infant was exposed to an average of 75.1 ± 42.6 painful procedures during the 14 days, resulting in a daily average of 5.4 ± 4.9 procedures per preterm.
The painful procedures performed and their frequency are presented in Table 1. of hospitalization in the neonatal services and were exposed to 1,957 (29.3%) painful procedures, followed by those submitted to ventilation and CPAP with 1,366 (20.4%) procedures, as shown in Table 3.    Table 4.

Discussion
In total, there were 6,687 painful procedures, with a daily average of 5.37 procedures per premature, a value lower than that found in previous studies conducted in other countries, with a similar methodological design.
In France (6) , In Brazil (9) , 32 newborns in intensive care and medium-complexity neonatal intermediary care were submitted to 1,316 painful procedures, recorded on a specific form during seven days of hospitalization, with a daily average of 5.9 procedures per newborn. Similar data were found in the retrospective review of records of 32 pediatric and neonatal units in Canada, identifying that 78.2% of the 3,822 children studied underwent at least one painful procedure in 24 hours, with a mean of 6.3 painful procedures per child (5) .
In the studies with data from records, whether using a specific questionnaire (6)(7)9,16) or the institution's printed form (5) , like in the present study, the limitation of possible underreporting of painful procedures should be considered.
Regarding birth weight, based on the classification of extreme low weight (less than 1,000 g), very low weight (less than 1,500 g), and according to the distribution of birth weights of preterm infants included in the study, the sample was classified in categories of weight up to 1,000g, from 1,001g to 1500g and greater than 1,500g. The results showed greater exposure to painful procedures in premature infants who presented lower birth weight, that is, in extremely low birth weight preterm infants.
The same occurs with gestational age: it is observed that, the more immature the newborn's classification, the greater the exposure to pain. Thus, the extreme premature infants, in addition to the biological risk inherent to maturity, are subject to the harmful consequences of repeated exposure to painful procedures (10) .
The findings of painful procedures, in relation to weight and gestational age, corroborate a study (6) where a statistically significant difference (p <0.001) was observed in the logistic regression model, comparing the exposure to painful procedures, associated with the use of sedation in newborns with gestational age between 37 and 42 weeks compared with the categories of preterm infants. It should be noted that, in the present study, painful procedures were not evaluated regarding the relationship between weight and gestational age (if birth weight for gestational age is adequate), which is a gap to be explored in future studies.
In the neonatal units studied, it is part of the protocols that clinical risk is assessed using SNAPPE II.
When analyzing the distribution of painful procedures according to SNAPPE II, in the score range ≥80, which represents a risk of 63.8% or more (17) , there was a greater exposure to painful procedures due to prematurity (101), that is, there is an indication that preterm infants in worse clinical condition receive more painful procedures. In addition, the preterm infants who spent the 14 days of data collection on invasive ventilation presented a proportionally higher number of painful procedures compared to those who spent the same period in ambient air, confirming study findings with a similar design (6) . Those preterm infants who have a more aggravated state of health and need greater procedural interventions to maintain survival are consequently more exposed to acute pain and its repeated effects.
Like in the results of this study, others also reported that the most frequent painful procedures performed in neonatal services are nasal / oral aspiration, followed by tracheal aspiration (6)(7) . This is justified by the fact that the studies are carried out in intensive care units, with a large number of infants requiring mechanical ventilation. In another study, developed at a unit of lower complexity (9) , the most frequent procedure was heel lance, a procedure that ranked seventh in this study.
This difference is due to the fact that, in the neonatal units in this study, venous and arterial blood collections were used for glucose measuring, according to the care planning, as a strategy to reduce the number of painful procedures in neonates at risk and as a neonatal pain management measure, as the heel lance is a more painful procedure (18) .
In the 32 investigated Canadian pediatric and neonatal units (5) , the most frequently performed Therefore, its use should be encouraged, and protocols based on specific evidence should be created in order to reduce manipulation and exposure to painful procedures.
As for the use of interventions for pain management, It is worth remembering, however, that the proper management of pain is considered a fundamental human right. Thus, it becomes a right of all people to have access to proper pain management without any discrimination, to acknowledge patients' pain and to provide information to them on the means available to evaluate and treat it, as well as access to appropriate evaluation and treatment by trained health professionals (19) . In Brazil, the right not to feel pain is In the present study, among the interventions used, the most frequent was the oral sucrose solution.
There are about 80 clinical trials and literature reviews and a systematic review on the use of this sweetened solution (13) . In a systematic review (22) , it was concluded that doses of 0.5 to 2 ml of sucrose (12 to 50%) administered orally two minutes before the painful procedure, combined with non-nutritive suction, reduce 1-2 points in the pain scale. In another review (23) , however, doubts are raised about the analgesic properties of sucrose, since the administration of this solution reduced the external manifestations of pain in newborns, such as facial movements, crying, heart rate and pain scores on single and multidimensional scales, when offered before acute painful procedures like the heel lance; some children showed cortical responses though, even without changes in facial expression.
These reflections have raised the possibility that reduced behavioral activity may not mean effective sedation, in addition to raising the issue of hyperalgesia (increased sensitivity to subsequent painful events) as a consequence of exposure to repeated painful procedures, which is still perceived even when sucrose is used, compared to placebo. It is concluded that there is a gap in the knowledge about the repeated use of sucrose as a gold standard measure for the management of neonatal pain (23) .
Other pharmacological interventions used less frequently for pain relief were continuous sedation necessary to obtain the desired analgesic effect (12) .
The efficacy and necessity of using pharmacological interventions to relieve neonatal pain are recognized and necessary in the scenarios that attend to premature neonates, but they have specific indications and undesirable side effects (12) . Local sedation has been used only once, however, but EMLA has shown to be effective for procedures such as venipuncture and lumbar puncture, with few side effects in neonates, more commonly methemoglobinemia and local hyperemia, when used properly (12) .
It is also worth mentioning the low use of maternal skin-to-skin contact, breastfeeding and maternal milk for the relief of acute neonatal pain, interventions considered more natural, with their proven benefits, including Brazilian research (14)(15) , and that permit the active participation of the mother in care for the child, besides being interventions nursing has autonomy to indicate and use in clinical practice. Especially for premature infants, the skin-to-skin intervention, in which the diaper-only newborn is positioned vertically between the mother's naked breasts and covered by a sheet or blanket, should be encouraged as, besides providing for mother / baby bonding, the mother influences the pain and stress response of the preterm infant (14) . however, painful procedures occur due to the need for the therapeutic and diagnostic implementation of the infant.
Thus, the health team, especially the nursing team, due to their constant contact and closeness to the premature infant, faces a challenge concerning pain management in neonatal services, in order to reduce the exposure of this population to painful procedures, avoiding unnecessary procedures, planning and grouping care, and to use interventions for pain relief.

Conclusion
It is observed that preterm infants are still submitted to high amounts of painful procedures, the most frequent type of procedure being oral / nasal aspiration. In addition, regarding the contextual factors, it is noted that preterm infants are more exposed to pain according to the birth (sex, birth weight, Apgar, gestational age and chronological age) and clinical conditions (clinical risk score, ventilation support, length of hospitalization and clinical diagnosis). It is also observed that there is under-treatment of the pain resulting from these procedures. Hence, the present study contributes to a more in-depth understanding of pain dimensioning in preterm infants and presents data to support future evidence-based actions to qualify pain management in preterm infants.