The practice of procedural pain assessment and management in neonatal intensive care unit in Ethiopia: Cross‐sectional study

Abstract Background and Aims Neonates in intensive care units undergo frequent painful procedures for diagnostic or care‐related purposes. Untreated pain has serious short‐term and long‐term complications. This study aims to evaluate the frequency of painful procedures, pain assessment, and their analgesic management practice among neonates admitted to the NICU. Methods The present study is a hospital‐based cross‐sectional study of neonates admitted at level II NICU of St. Paul hospital millennium medical college in Ethiopia between March and August 2019. Data were collected from medical charts of neonates and bedside observation using a checklist. The parameters included were demographic characteristics, types of painful procedures, pain assessment practice, and analgesic intervention provided during painful procedures. Descriptive statistics, Mann‐Whitney U‐test, and Kruskal‐Wallis test were used to compare the number of painful procedures and influencing factors. P‐value < .05 was considered statistically significant. Results Of the 325 neonates included in this study, a median of 4 (3‐7) painful procedures were performed per neonate in the first 24 hours of NICU stay. Heel lance 280 (20.7%) and Venipuncture 249 (18.41%) were the most commonly performed painful procedures. Of the 1352 painful procedures, none of the neonates received any form of analgesic intervention and none of the neonate's pain scores were documented on their medical chart. The higher number of painful procedures were associated with gestational age between 28 and 31 weeks, birth weight less than 1500 g, and use of CPAP respiratory support P‐value <.001, <.001, and .0015, respectively. Conclusion Painful procedures were frequently performed in NICU without any form of analgesic intervention. Strategies to introduce neonatal pain assessment and their analgesic management for clinical practice are necessary.


| INTRODUCTION
Neonates admitted to neonatal intensive care units (NICU) undergo multiple diagnostic or care-related painful procedures during their hospitalizations. In NICU, each neonate experiences an average of 7.5 to 17.3 painful procedures per day in which most of the procedures is ranged from moderate to severe pain. [1][2][3][4] The most frequently performed painful procedures were heel lance, suctioning, venipuncture, and peripheral IV insertion. [5][6][7][8][9] Despite the misconception regards to neonatal pain in the past years, scientific evidence indicates that pain pathways are active and functional as early as 25 weeks of gestation. 10 Under-treated pain experienced in the early life of the neonatal period can cause physiological and behavioral changes, which may lead to detrimental long-term consequences of altered pain sensation, neuro-behavioral changes, and learning disabilities in later life. 11,12 Prevention of pain and provision of optimal pain control strategies should be an essential part of standard health care in the NICU. 13,14 Medical knowledge and perception of neonatal pain and analgesic strategies have been improved among healthcare providers; however, the clinical practice remains unchanged. 15,16 Scientific evidence demonstrates the analgesic efficacy of nonpharmacological pain relief strategies 17,18 including breastfeeding, skin-to-skin contact, sweet solutions, multisensorial stimulation, and also pharmacological strategies 19 to control procedural pain in neonates. However, in the neonatal unit of our hospital, the routine painful procedures are performed without any form of pharmacological and non-pharmacological measures.
In the developed world, despite the recommendations and guidelines based on evidence, procedural pain in neonates continues to be inconsistently assessed and inadequately managed. [20][21][22] Consequently, in China and sub-Saharan African countries, painful procedures are performed without any form of pain control measures. 3,8 In resources limited countries including Ethiopia, neonatal pain management has not been part of neonatal care where the focus has been confined to saving the lives in need.
Furthermore, resource-scarce to procure analgesic medication, knowledge deficit, and lack of institutional guidelines remains major challenging issues to implement in clinical practice. [23][24][25] Overcoming these problems is vital as an attempt to improve pain management practice in neonates.
As far as our search, no studies have been done on this major clinical problem in Ethiopia. This prospective cross-sectional study was conducted to evaluate the practice of procedural pain assessment and analgesic management among neonates admitted to NICU.

| Study design and participants
A hospital-based prospective cross-sectional study was conducted over 6 months between March 2019 and August 2019 in St. Paul's hospital millennium medical college. This study is done as per the declaration of Helsinki ethical principles for medical research involving human subjects' protocol. Ethical clearance was received from the ethical committee of the institution and written informed consents were obtained from the legal guardian or parents. This study is registered at www. Research registry with research registry UIN: researchregistry7419.
All neonates admitted to level II NICU with postnatal age of fewer than 7 days and gestational age of >28 weeks and successful attempts of painful procedures were included in this study as shown in Figure 1. Neonates transferred or discharged to another unit before 24 hours of admission and neonates with altered levels of consciousness that affect movement and facial expression were excluded from the study.

| Sample size and sampling techniques
The outcome variables of our study were to determine the number of painful procedures, evaluate the practice of pain assessment, and analgesic intervention during the first 24 hours of NICU admission.
The sample size was calculated by using the single population proportion formula. The following assumptions were used to compute the sample size; the prevalence of procedural pain (69.6%) was taken from the preliminary data conducted in Netherlands 22 with a 95% confidence interval, a 5% margin of error, and a 5% attrition rate, the total sample size was 340 study participants. Based on the review of the logbook and registration system of neonates admitted to NICU in the previous year, an average of 690 neonates in 6 months were admitted to this unit.
A systematic random sampling technique was used to select study participants. The sampling interval k was calculated to be 2 using the formula: k = N/n (690/340); where n = total sample size, N = population per 6 months. From all neonates who fulfilled the inclusion criteria, the samples were selected skipping every two intervals. The first participant was selected by lottery method from the first admission day with every two intervals.

| Data collection techniques
Data were collected from medical charts and checklists developed based on previous literature. Before data collection, training of 3 days was offered for data collectors regards to overall data collection process including NIPS observation and inter-rater reliability were measured.
The research team consisted of trained general practitioners, NICU nurses, and pediatricians who compiled a checklist containing all types of daily performed painful procedures. The designed checklist included a list of 11 different procedures routinely performed and considered painful by the team, as shown in Table 1.
Data of demographic characteristics and primary admission diagnosis were collected immediately when the sick neonates were admitted to the NICU from their medical charts.
Frequency and type of painful procedures, NIPS score, and analgesic intervention were collected by bedside observation in real time. The data collection was continued for the first 24 hours of NICU admission.
Neonatal infant pain scale (NIPS) was used to evaluate the intensity of pain on each procedure for 1 minute to fully assess each indicator and graded from 0 to 7. This pain scale assesses six behavioral indicators (facial expression, cry, breathing pattern, arms, legs, and state of arousal) in response to painful procedures in preterm and term neonates and has shown good inter-observer reliability. 26,27 The collected data were cross-checked by the principal investigator to ensure accuracy and completeness.

| Statistical analysis
Data were coded and entered into SPSS software for Windows (version 26, SPSS Inc., Chicago, Illinois) was used for the statistical analysis of the data. The Shapiro-Wilk test was used to test the normality of the distribution of data.
Nonparametric continuous variables were expressed as median and interquartile range (IQR), and categorical variables as frequency and percentage (%, n/N).
Influencing factors and the number of painful procedures were compared between groups using unpaired t-test and analysis of variance for parametric data, the Mann-Whitney U-test, or the Kruskal-Wallis test for nonparametric data. P-value < .05 on the two-sided test was considered to be statistically significant.

| Operational definitions
Painful procedure: Any care-related or diagnostic interventions that have some degree of pain associated with it.
Skin breaking and non-skin breakings: Procedures were classified as skin breaking if they involved a penetration to the skin (eg, heel stick, injections) and non-skin breaking if they did not penetrate the skin surface (eg, gastric tube and nasal cannula insertion). 28 Procedural pain: Pain related to either diagnostic or care-related procedures.     (Table 1).

| Pain assessment and their analgesic management practice in NICU
There were no validated protocols or guidelines for routine neonatal pain assessment and analgesic management in the study area during the study period. As a result, pain scores were not documented on the medical charts of neonates who were exposed to painful procedures.
Similarly, none of the neonates received any form of analgesic intervention before and during painful procedures. The average mean NIPS score observed in this study was 5.08 ± 1.23. All procedures included in this study were painful in which the majority, 64.3%, of procedures ranged from moderate to severe pain intensity, while the rest 35.7% of procedures were associated with mild to moderate pain.

| Factors influencing the number of painful procedures
Factors influencing the number of painful procedures performed during the first day of admission are shown in Table 3.
In terms of gestational age, the median number of painful procedures performed on neonates between 28 and 31 weeks of gestation was significantly higher compared with the median value of neonates between 32 and 36 weeks of gestation and older than 37 weeks of gestation with a P-value <.001. The median number of painful procedures performed according to birth weight was significantly lower on neonates, weighing <1500 g compared with neonates between 1500 and 2500 g and greater than 2500 g P-value <.001, whereas the median value of neonates weighing 1500 to 2500 g and >2500 g demonstrated an insignificant difference P-value = .215.
The median number of painful procedures performed on neonates who received oxygen support via CPAP was higher compared with other P-value = .015. There was no significant difference observed between gender P-value = .165. However, the median value between 32 and 36 weeks and older than 37 weeks of gestation demonstrate an insignificant difference P-value = .762. Another systemic review of observational study 1 also reported an average of 7.5 to 17.3 per neonate per day.
This discrepancy might be related to the fact that this study was conducted in a level II NICU setting in which relatively lower intervention is required. Secondly, the large majority of neonates were >37 weeks of GA and only 7% were <31 weeks of GA.in our study. Moreover, the number In terms of factors influencing the number of painful procedures, previous studies observed that preterm infants at the lowest gestational age, 2,4,5,8 very low birth weight, 2 and neonates receiving CPAP support 3,4,6 were exposed to a higher number of painful procedures.
Similarly, despite GA and birth weight being strongly correlated, the present study observed that preterm neonates between 28 and 31 weeks of gestation, birth weight <1500 g, and neonates who received CPAP support were exposed to a higher number of painful procedures compared with others. In disagreement with our findings, other studies found no statistically significant difference between the number of painful procedures as compared with gestational age 6,7,9 and birth weight. 7 The variation of the statistical analysis method used in their study and ours to determine the association between independent and outcome variables could explain the observed difference.

| Strength of the study
We used a relatively larger sample size and prospective study design.

| CONCLUSION
Our study observed that neonates admitted to NICU were exposed to frequent painful procedures during the first 24 hours of hospitalization. Heel lance was the most commonly performed procedure.
Preterm neonates between 28 and 31 weeks of gestational age, birth weight less than 1500 g, and those who require respiratory support experienced more frequent painful procedures. None of the procedures are accompanied by any form of analgesia intervention.
We hope that our findings in the practice of pain assessment and management in neonatal pain can bring attention to this clinical activity. Based on our results, we recommend implementing the guidelines of neonatal pain assessment and management in neonatal care centers.

ACKNOWLEDGEMENTS
Our appreciation goes to St. Paul's hospital millennium medical college for giving us ethical clearance. Our thanks also go to data collectors and the family or guardians of study participants who were involved during the data collection period.

FUNDING
The author(s) received no financial support for the research, authorship, and/or publication of this article.

CONFLICT OF INTEREST
The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
All authors have read and approved the final version of the manuscript.
Dereje Zewdu had full access to all of the data in this study and takes complete responsibility for the integrity of the data and the accuracy of the data analysis.

TRANSPARENCY STATEMENT
Dereje Zewdu affirms that this manuscript is an honest, accurate, and transparent account of the study being reported; that no important aspects of the study have been omitted; and that any discrepancies from the study as planned (and, if relevant, registered) have been explained.

DATA AVAILABILITY STATEMENT
Data are available from the corresponding author upon reasonable request.