Neonates experience procedural pain (eg, from vitamin K injections, immunizations, and heel sticks for screening tests) as a part of routine neonatal care during the first days of life.1 A considerable number of newborns require hospital treatment immediately after birth due to medical conditions, such as infection, congenital anomaly, respiratory failure, low birth weight,2 and premature birth before the 37th gestational week.3 Prematurity is also the most common reason for admission to the neonatal intensive care unit,3 where painful medical and nursing procedures are part of the required care.4,5
Several studies have quantified the painful procedures performed on hospitalized neonates. The most common painful procedures in neonates are heel lance, intramuscular injection, and venipuncture. The heel lance is a common procedure in both pre- and full-term neonates,6 but the exposure to pain varies between neonates. It has been observed that neonates experience a median of 16 painful procedures every day during the first 14 days of hospitalization, but the youngest newborns – as well as those with the most severe problems – experience up to 62 procedures per day.
Providing neonates with effective pain management is a priority from an ethical perspective as well as to mitigate the potential adverse effects of pain.7 Repeated procedural pain without sufficient pain alleviation during neonatal care has been shown to have adverse short- and long-term effects on physical, cognitive, and brain development in neonates born before the 32nd gestational week. Frequent procedural pain is associated with delayed early postnatal body and head growth,8 and with slower head circumference growth at six- and 12-months corrected age.9 The number of skin-breaking procedures experienced by a neonate is negatively correlated with cognitive outcomes at 18-months corrected age,10 while further research has shown that skin-breaking procedures contribute to abnormalities in the white matter microstructure of the brain and a lower intelligent quotient at school age.11
Despite evidence that pain during the neonatal period can cause long-term consequences, procedural pain appears to be undertreated.7 The current knowledge base indicates that non-pharmacological interventions, such as oral sucrose, skin-to-skin contact (SSC), containment/facilitated tucking, non-nutritive sucking and breastfeeding are suitable for alleviating the pain caused by small procedures.7 Using oral sucrose alone or with non-nutritive sucking is the most frequently studied non-pharmacological method for procedural pain management in neonates. Sucrose is effective in alleviating the procedural pain related to skin-breaking procedures (eg, heel lance, venipuncture, and intramuscular injection) in full- and pre-term infants.12
Skin-to-skin contact, during which a naked, diaper-dressed infant is placed on the caregiver's bare chest, provides a natural opportunity for the baby's parents to participate in pain management. There is empirical evidence that SSC reduces the pain caused by heel lance and intramuscular injection.13 The effectiveness of SSC appears to be unaffected by whether the provider is the mother or another person, and no side effects have been reported for this method.13 Facilitated tucking also allows parents to be involved in relieving their baby's pain.14 During endotracheal suctioning, the facilitated tucking position – relative to routine care – is effective at managing pain in pre-term neonates, although it does not demonstrate a significant advantage over oral glucose or opioids when used during heel stick.14
However, non-pharmacological pain relief methods also have certain limitations. For example, there is currently insufficient evidence that oral sucrose is effective at reducing the pain caused by some procedures, such as arterial puncture or nasogastric tube insertion.12 It is also possible that repeated doses of sucrose in very pre-term neonates may not be safe.15 The appropriate dose of SSC, its effects over repeated use, and suitability for neonates of different gestational ages remain unclear due to the heterogeneity of previous studies.13 In summary, there is not enough evidence to deem one of the aforementioned non-pharmacological interventions as the superior technique for pain management. Each of these methods provides some pain relief for neonates, but is not completely effective.16
The use of technology-based interventions in the treatment of pediatric pain has increased over the past years; for example, two recent systematic reviews investigated the effectiveness of vibratory stimulation for needle-related procedural pain management in children.17,18 The reviews revealed that the vibrator device was able to significantly reduce self-,17,18 parent-,17 and observer-reported procedural pain.17,18 There is also some evidence that virtual reality distraction is effective at relieving pain among children. Studies have found that virtual reality interventions can relieve needle-related pain,19 pain related to burn wound cleaning,20 and dental treatment.21 Nevertheless, there remains limited empirical evidence on how effective virtual reality is at relieving pain among children.22 Humanoid robots represent the latest technology for procedural pain management in children.23-25
In summary, previous systematic reviews that have evaluated whether technology-based interventions are effective for pain management in pediatric patients have focused on children and/or adolescents aged 0 to 18 years.17,18,22,24 Neonates were only covered by the work of Ueki et al.,18 with one of the included randomized controlled studies evaluating the effectiveness of vibratory stimulation in alleviating pain among neonates during heel stick. It is important to note that technology is becoming increasingly prevalent in neonatal care26; as such, it would be useful to investigate the effectiveness of technology-based methods in neonatal pain management. A preliminary search of PROSPERO, MEDLINE, the Cochrane Database of Systematic Reviews, and JBI Evidence Synthesis was conducted, with no current or in-progress systematic reviews on the topic identified.
What is the effectiveness of technology-based interventions at relieving procedural pain in hospitalized neonates compared with other non-pharmacological interventions?
This review will consider studies that include both hospitalized full-term neonates (> 37 completed weeks postmenstrual age) and pre-term neonates (< 37 completed weeks postmenstrual age) to a maximum postpartum age of one month or with a corrected age, who are undergoing a procedure that may cause pain.
This review will consider technology-based, non-pharmacological intervention studies that evaluate how effective a certain intervention is at managing procedural pain in hospitalized neonates. In the context of this review, technology refers to an electronic device or computer technology. Several examples of technological interventions that can be considered include mechanical vibration or vibrator, transcutaneous electrical nerve stimulation, games, audio intervention, virtual reality, and robots.
This review will consider studies that compare a technology-based intervention with an alternative non-pharmacological intervention, including, for example, breastfeeding, facilitated tucking, holding, live music, non-nutritive sucking, rocking, sensorial saturation, SSC, swaddling, oral sucrose, and combinations of non-pharmacological interventions. The review will not include studies comparing technology-based interventions with other technology-based interventions.
To understand whether technology-based interventions are effective at alleviating pain in neonates following a painful procedure, this review will consider studies that describe the outcome of procedural pain; that is, the response to a painful procedure as measured by at least one of the following:
- Pain scores measured using a validated pain assessment scale for neonates (eg, COMFORT27; Neonatal Infant Pain Scale [NIPS]28; Neonatal Pain, Agitation and Sedation Scale [N-PASS]29; Premature Infant Pain Profile [PIPP]30; or Premature Infant Pain Profile-Revised [PIPP-R]31);
- Behavioral indicators (eg, cry duration, facial expressions);
- Changes in physiological indicators (eg, changes in heart rate, respiratory rate, oxygen saturation, near-infrared spectroscopy).
- Recovery from the procedure (time during which the measured pain indicator returns to the baseline value);
- Adverse effects of the intervention (eg, apnea, bradycardia, desaturation).
These indicators will be categorized as “yes” or “no.”
Types of studies
This review will consider both experimental and quasi-experimental study designs, including randomized controlled trials, non-randomized controlled trials, and randomized cross-over trials.
This systematic review will be conducted in accordance with JBI methodology for systematic reviews of effectiveness.32 This protocol is registered in PROSPERO CRD42021254218.
The search strategy will aim to identify both published and unpublished studies. In accordance with the JBI methodology for systematic reviews, a three-step search strategy will be used for this review.32 An initial, limited search of the MEDLINE (Ovid) and CINAHL (EBSCO) databases will be undertaken to identify articles on the topic, followed by an analysis of words in the titles and abstracts of potentially relevant articles, along with the search terms used to describe the articles. A second search, including the relevant identified keywords and index terms, will then be performed in all of the included databases. The search strategy developed for MEDLINE (Ovid; see Appendix I) will be adapted for each separate database and/or information source. In the third step of the search, the reference lists of all included sources of evidence will be screened for additional studies that may have been missed during the first two searches. Studies published in English, Swedish, and Finnish will be included. There will be no restrictions regarding the date of publication.
MEDLINE (Ovid), CINAHL (EBSCO), Scopus, the Cochrane Central Register of Controlled Trials, and the Finnish database MEDIC, will be searched. In-progress and recently completed studies will be identified from clinical trial registers. MedNar and ProQuest Dissertations and Theses Global will be searched for unpublished studies.
Following the search, all identified citations will be collated and uploaded into Covidence (Veritas Health Innovation, Melbourne, Australia) systematic review software, and duplicates will be removed. Following a pilot test, titles and abstracts will be screened by two independent reviewers against the inclusion criteria for the review. The full-text versions of potentially relevant studies will then be retrieved and imported into the JBI System for the Unified Management, Assessment and Review of Information (JBI SUMARI; JBI, Adelaide, Australia).33 Full-text articles will then be assessed in detail against the inclusion criteria by two or more independent reviewers, and reasons for exclusion will be recorded and reported in the systematic review. Any disagreements that arise between the reviewers at each stage of the selection process will be resolved through discussion or via an additional reviewer. The results of the search and the study inclusion process will be reported in full in the final systematic review and presented in a Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) flow diagram.34
Assessment of methodological quality
Eligible studies will be critically appraised for methodological quality by two independent reviewers using standardized critical appraisal instruments from JBI for experimental and quasi-experimental studies.32 Where data are missing or additional information is needed for clarification, the authors of the paper will be contacted. Any disagreements that arise will be resolved through discussion or, if this is not possible, by including a third reviewer. The results of the critical appraisal will be reported in narrative form and in a table.
All studies, regardless of the results of their methodological quality, will undergo data extraction and synthesis, where possible. The quality of the studies will be considered in the interpretation of results.
Data will be extracted from studies included in the review by two independent reviewers using the standardized data extraction tool in JBI SUMARI.33
The extracted data will include specific details about the participants (eg, gestational age, postpartum age, condition of health), study methods, interventions (eg, type of technology-based intervention, type of comparison), and outcomes (eg, score on a pain scale). Any disagreements that arise between the reviewers will be resolved through discussion or, if this is not possible, by including a third reviewer. Attempts will be made to contact the research team if any data are missing from a certain study.
Studies will, whenever possible, be pooled in a statistical meta-analysis using JBI SUMARI.33 Effect sizes will be expressed as odds ratios (for dichotomous data) and weighted (or standardized) final post-intervention mean differences (for continuous data). The corresponding 95% confidence intervals will also be calculated and presented. Heterogeneity will be statistically assessed using the standard χ2 and I2 tests, and subgroup analysis for full-term and pre-term infants will be considered. Statistical analyses will be performed using fixed-effects or random-effects models for meta-analysis based on the guidance by Tufanaru et al.35 Experimental data concerning each distinct outcome (eg, PIPP score after procedure, heart rate after procedure) will be synthesized in separate meta-analyses. Sensitivity analyses will be carried out to test whether the methodological quality or heterogeneity of the studies influence the results. Where statistical pooling is not possible, the findings will be presented in narrative form, including tables and figures to aid in data presentation Whenever 10 or more studies are included in a meta-analysis, a funnel plot will be generated to assess publication bias. Statistical tests for funnel plot asymmetry (Egger test, Begg test, Harbord test) will then be performed.
Assessing certainty in the findings
The Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach will be used to assess confidence in the quality of evidence.36 The results of this assessment will be shown in a Summary of Findings (SoF) created using GRADEPro software (McMaster University, ON, Canada). The SoF will present absolute risks for treatment and control, estimates of relative risk, along with a ranking of the quality of evidence based on study limitations (risk of bias), indirectness, inconsistency, imprecision, and publication bias. The outcomes reported in the SoF will be: pain score during procedure, pain score after procedure, changes in physiological indicators during procedure, physiological indicators following procedure, duration of cry following procedure, and duration of recovery after procedure.
Appendix I: Search strategy
Search conducted on November 11, 2020
Records retrieved: 617
Language limits: English, Finnish, Swedish
#1 (infant∗[Abstract, Title] or newborn∗[Abstract, Title] or baby [Abstract, Title] or neonate∗[Abstract, Title] or “premature infant”[Abstract, Title] or preemie∗[Abstract, Title])
#2 Infant [MeSH, Explode]
#3 #1 OR #2
#4 (“pain management”[Abstract, Title] or “pain care”[Abstract, Title] or “pain treatment” [Abstract, Title] or “pain alleviation” [Abstract, Title] or “pain relief” [Abstract, Title])
#5 Pain Management [MeSH, Explode]
#6 (“procedural pain” [Abstract, Title])
#7 #4 or #5 or #6
#8 Technology [MeSH, Explode]
#9 (“technology-based” [Abstract, Title] or technolog∗ [Abstract, Title] or vibrat∗[Abstract, Title] or buzzy [Abstract, Title] or TENS[Abstract, Title] or player∗[Abstract, Title] or record∗[Abstract, Title] or headset∗[Abstract, Title] or computer [Abstract, Title] or mobile [Abstract, Title] or virtual∗[Abstract, Title] or robot∗[Abstract, Title] or video∗[Abstract, Title] or device∗[Abstract, Title] or mechanic∗[Abstract, Title])
#10 #8 or #9
#11 #3 and #7 and #10
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