Abstract
Background
Placement of a peripherally inserted central catheter (PICC) is a clinically essential but painful procedure commonly performed in neonates. Early exposure to pain is associated with negative sequelae and therefore pain should be managed. Various non-pharmacological and/or pharmacological interventions have been used in clinical practice. However, the optimal pain management strategy is unclear. The primary objective of this systematic review and meta-analysis is to evaluate the benefits and harms of pain management interventions in neonates undergoing PICC placement.
Methods
Databases were searched for randomized controlled trials (RCTs) from inception to March 2024. The literature search was updated in June 2025 and no additional eligible articles were identified for inclusion. Title and abstract screening, full-text screening and data extraction were performed in duplicate. Risk of bias was assessed using Cochrane’s risk of bias (RoB) 2.0 tool. The critically important outcome was pain measured using validated tools including unidimensional behaviour and multidimensional (comprising combinations of contextual, behavioural and/or physiological components) tools. Secondary outcomes included procedure success and adverse events. Pooled effect estimates were standardized mean difference (SMD) and relative risk (RR) with 95% confidence intervals (CI) using random effects models. A GRADE assessment of the overall certainty of the evidence for each outcome was completed.
Results
Six included studies reported pain scores for between-group comparisons of pain management interventions among 324 neonates. The interventions included intravenous opioids (morphine, remifentanil), topical anesthetics (tetracaine) and intravenous acetaminophen. Morphine was effective in reducing acute pain compared to control (SMD −0.65 [95% CI −1.17, −0.13]) using a unidimensional tool (brow bulge) in one study. Using two different multidimensional tools, remifentanil was effective in reducing acute pain compared to control (SMD −1.59 [95% CI −2.21, −0.97] using the premature infant pain profile [PIPP] and SMD −1.21 [95% CI −1.79, −0.62] using the neonatal infant pain scale). In a meta-analysis of two RCTs comparing tetracaine to placebo, there was no difference in acute pain (SMD −0.05 [95% CI −1.70, 1.59], I2 = 0%) or overall procedural pain (SMD −0.19 [95% CI −2.07, 1.69], I2 = 0%) using PIPP scores. For acetaminophen, there was no difference in pain scores across three dosing regimens. Across all intervention comparisons, there was no difference in procedure success and no serious adverse events attributed to pharmacological interventions. There was moderate certainty of evidence for all critical and important outcomes.
Discussion
Based on available evidence, opioids probably reduce pain associated with PICC placement in neonates. Topical anesthetics and acetaminophen were not demonstrated to be effective. Further research is necessary to guide healthcare professionals in implementing optimal pain management for this procedure.
Keywords: Infant, Newborn, PICC placement, Pain measurement, Pain management
INTRODUCTION
Infants admitted to the neonatal intensive care unit (NICU) are exposed to multiple invasive procedures as part of their clinical management (1). Pain management strategies are important to implement in neonatal care as pain has been associated with short- and long-term negative sequelae including suboptimal brain development, alterations in pain responsivity and changes in motor and cognitive functioning (2–9). Many hospitalized neonates require long-term vascular access for administration of parenteral nutrition and medications. This can be achieved by the placement of a peripherally inserted central catheter (PICC), which elicits moderate to severe pain responses (10). The procedure entails insertion of an intravenous (IV) needle through which a catheter is threaded into the vein to reach a large blood vessel followed by securement of the PICC with a sterile dressing. Several elements of this procedure, however, contribute to pain and include application of a tourniquet for vessel distension prior to the IV needle puncture, the needle puncture itself, manipulation or hyperextension of the extremities for catheter threading, positioning to allow for imaging to confirm catheter placement and securement of the PICC with a site dressing (11,12). PICC placements compared to peripheral venous catheters are undertaken for many reasons, including reduction in the number of repeated skin punctures needed to obtain IV access and potentially decreased incidence of sepsis from repeated skin breaks. A PICC can typically remain in situ for several weeks (10,13).
Despite the deleterious effects of neonatal pain and readily available pain management guidelines by professional organizations, pain management strategies continue to be underutilized in NICUs (14–19). There are currently no established protocols for procedural analgesia during PICC placement. Traditionally, pain management strategies have been categorized into non-pharmacological interventions (e.g., non-nutritive sucking and sweet-tasting solutions [e.g., sucrose]) and pharmacological interventions (e.g., opioids) or a combination of both (20–23). These interventions are used at the discretion of the caregivers who are entrusted with optimal care of these critically ill neonates. Based on surveys of healthcare providers, there is reluctance to employ pharmacological pain management strategies, especially opioids, due to concerns of cardiovascular and respiratory adverse events (24,25). However, it is an ethical obligation of healthcare providers to minimize procedural pain endured by neonates.
The objective of this systematic review and meta-analysis was to synthesize results from randomized controlled trials (RCTs) evaluating pain management strategies in neonates undergoing PICC placement, with the goal of identifying evidence-based analgesia for PICC placement in the NICU.
METHODS
The protocol for this systematic review and meta-analysis was prepared in adherence with the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols (PRISMA-P) statement and is registered with the international prospective register for systematic reviews PROSPERO (CRD42017060346) (26,27). The Grading of Recommendations, Assessment, Development and Evaluation (GRADE) framework and methodologies outlined in the Cochrane Handbook for Systematic Reviews of Interventions were employed for this systematic review and meta-analysis (28,29). The PRISMA guidelines were followed for reporting of results (30).
Inclusion/exclusion criteria: RCTs and quasi-randomized RCTs with between-group parallel design that enrolled neonates admitted to the NICU and undergoing PICC placement were eligible for inclusion. Conference proceedings or abstracts, review articles, letters, commentaries and editorials were excluded. No restrictions to year of publication or language were applied. Interventions included single and combination of interventions used for PICC placement, while comparators included control with or without the standard of care (e.g., non-pharmacological interventions) or active comparison as specified in the studies. The additive benefit of one intervention over another was also evaluated if data were available from the study.
Outcomes of interest: The outcomes of interest were categorized into critically important and important as per GRADE methodology and our previously described methods (28,31). Pain assessed using validated unidimensional behaviour and multidimensional (comprising contextual, behavioural and/or physiological components) scales was the critical outcome. Due to their non-specificity with regard to pain responses, physiological parameters in isolation were not considered.
Based on available data, the critical pain outcomes were assessed at multiple timepoints during the PICC placement: 1) the baseline phase before the procedure, 2) the skin preparation phase, 3) the acute pain phase (needle puncture and catheter threading) and 4) the recovery phase, where the infant is returned to a comfortable position after the procedure has ended. For studies that provided data for the entire procedure, an overall procedural pain score was used in the analysis. Important outcomes were procedural, including procedure success, number of procedure attempts, procedure duration and adverse events (e.g., cardiorespiratory effects with opioids or transient changes in skin at the site of application for topical anesthetics).
Information sources and search strategy: The search strategy was developed in collaboration with the information specialist (E.U.) (Appendix 1). The following databases were searched from their inception to March 2024: Cochrane Central Register of Controlled Trials (Wiley), MEDLINE (Ovid), Embase (Ovid), CINAHL (EBSCOhost) and APA PsycInfo (OvidSP). Reference lists of studies eligible for inclusion were reviewed for relevant articles not identified in the primary search. The literature search was updated in June 2025 and no additional eligible articles were identified for inclusion.
Selection process and data extraction: Retrieved citations were imported into EndNote (Philadelphia, PA, USA) (32). Two reviewers (N.T., V.S.) independently screened titles and abstracts for studies that could potentially meet inclusion criteria, using components of the research question and study design. After de-duplication and initial screening, a full-text review was conducted independently by the same two reviewers to identify studies for inclusion. Reviewers were not blinded to the authors or settings of the studies. Reasons for study exclusion were recorded at this stage. Disagreements were resolved by discussion or consultation with a third reviewer (A.T.) if consensus could not be reached. Each reviewer was blinded to other reviewers’ screening and study selection. Additional studies were identified from reference lists of eligible studies for inclusion. Data extraction was performed independently by two reviewers (N.T., V.S.) using a standardized piloted data collection form which included study author, country, year of publication, patient characteristics, inclusion and exclusion criteria, procedural details, details of pain management strategies and critically important and important outcomes.
Data from intention-to-treat and per-protocol analyses were recorded as appropriate. Continuous data were extracted as mean and standard deviation (SD) or median and interquartile range (IQR) along with sample sizes. If median and IQR were reported for continuous outcomes, mean and SD were approximated using the Wan method (33). Categorical data were collected as counts and a continuity correction of 0.5 was applied using the modified Haldane–Anscombe method to compute relative risk (RR) when a zero-count was recorded (34). If studies included multiple treatment arms, they could contribute to several analyses (i.e., the same study could provide data for several clinical questions). All authors of the included studies were contacted for missing data or clarifications when required. No individual participant data were sought. Disagreements between data abstractors were resolved by discussion first, followed by a third reviewer (A.T.).
Steps were undertaken to provide unique identifiers for included studies in the software programs used to conduct the review. Studies were identified using the following notation: “First Author” “Year of Publication” (e.g., Taddio 2006). If studies contributed to multiple analyses, then “(#)” was added to enable their discernment (e.g., Taddio 2006 [1]).
Assessment of methodological quality of included studies: Two reviewers (N.T., V.S.) used the Cochrane risk of bias tool (RoB 2.0) to independently assess the risk of bias of included studies in the following five domains: randomization process, deviation from intended interventions, missing outcome data, outcome measurement and selection of reported results (35). Overall, each study was assigned as low risk, some concerns, or high risk of bias based on the worst rating in any individual domain. Disagreements in risk of bias assessment were resolved by discussion or a third reviewer (A.T.).
Data synthesis and statistical analysis: Continuous data were combined using mean difference or standardized mean difference (SMD) with 95% confidence interval (CI) as appropriate with SMDs of 0.2 representing a small effect, 0.5 a moderate effect and 0.8 a large effect (29). Categorical data were combined using RR and 95% CI. All meta-analyses followed a random effects model. Clinical heterogeneity was evaluated by assessing differences in the following characteristics: age of participants, procedural details and healthcare professionals performing the procedure and outcome assessment methods. Statistical heterogeneity was assessed using the Ι2 statistic and interpreted as follows: <40% negligible heterogeneity, 30–60% moderate heterogeneity, 50–90% substantial heterogeneity and 75–100% considerable heterogeneity (36).
If a study included assessments of the same outcome measure at multiple timepoints, the data were combined into a single-point estimate and associated variance using established statistical methods and an estimated correlation of 0.25 (37). This comprehensive approach to data synthesis resulted in the ability to include all the data pertaining to outcomes in the meta-analysis and minimize potential bias. If >10 studies were identified for comparison for any outcome, a funnel plot was planned to assess publication bias. All statistical analyses were conducted in R version 4.3.2 (Vienna, Austria) (38).
Each outcome was assessed using the GRADE approach across the following domains: risk of bias, imprecision, inconsistency, indirectness and publication bias (28). GRADEpro was used to generate a summary of the findings in table (39). Certainty of evidence was interpreted as very low, low, moderate or high.
RESULTS
The database searches yielded 10,346 citations and an additional two citations were identified separately from manual searches. All references were inputted into an EndNote library that identified 1448 duplicates. The remaining 8898 citations were reviewed by two independent reviewers (N.T., V.S.) against the eligibility criteria. After title and abstract screening, 11 reports were assessed for eligibility at the full-text review stage of which five studies did not meet the inclusion criteria. Reasons for the exclusion of the five reports include: letter (40), commentary (41) wrong patient population (42), wrong intervention (43) and missing critical outcome (44). Of the two reports that were identified from reference lists of eligible studies, both were excluded due to: abstract (45) and wrong study design (46). The PRISMA flow diagram is presented in Figure 1.
Figure 1.
Flow diagram of study identification and selection
Characteristics of included studies are described in Table 1. Altogether, 347 neonates were included from six eligible studies. The sample size in included RCTs ranged from 14 to 111 participants. Of the six included studies, three studies evaluated the effectiveness of opioids for PICC placement. The study by Lago et al. evaluated IV remifentanil to a placebo infusion, the study by Shin et al. evaluated two doses of IV remifentanil (0.25 μg/kg/minute vs. 0.1 μg/kg/minute) while the study by Taddio et al. compared the efficacy of IV morphine alone compared to topical tetracaine alone or a combination of IV morphine and topical tetracaine (48,49,51). Lemyre et al. and Ballantyne et al. evaluated the effectiveness of topical tetracaine compared to a placebo gel, while the effectiveness of tetracaine from the study by Taddio et al. was obtained by comparing the tetracaine group to a combined IV morphine and tetracaine group and an IV morphine alone group (50–52). One study by Roofthooft et al. evaluating three different doses of IV acetaminophen for PICC placement was also included in this review (47). All of the studies used between-group parallel designs. Results from the study by Shin et al. are qualitatively described as it was not possible to combine available data (48).
Table 1.
Characteristics of included trials
| First author, year, country | Population enrolled, design, setting | Population exclusion criteria | Intervention details | Critical outcomes | Important outcomes |
|---|---|---|---|---|---|
| Roofthooft (47), 2017, Netherlands | N = 60; Infants < 32 weeks GA with an indwelling arterial catheter and requiring PICC in the first week of life Between-group design Multicenter, NICUs |
Infants with prior receipt of any analgesic or sedative (except for NSAID for PDA treatment) | Acetaminophen (Perfalgan©; Bristol-Meyers Squibb) 10 mg/kg IV (n = 20) or Acetaminophen 15 mg/kg IV (n = 20) or Acetaminophen 20 mg/kg IV (n = 20) Acetaminophen was administered 15 minutes before the procedure Experienced neonatologists or nurse practitioners performed the procedure |
PIPP, COMFORTneo | None |
| Shin (48), 2014, Korea | N = 14 (2 infants did not receive interventions) Mechanically ventilated infants <32 weeks GA Between-group design Multicenter, 2 NICUs |
Infants with major congenital anomalies, cardiopulmonary instability, grade III or IV IVH, previous prior receipt of sedatives, antiepileptics or anesthetics | Remifentanil 0.1 µg/kg/minute IV infusion (n = 5) or Remifentanil 0.25 µg/kg/minute IV infusion (n = 7) Remifentanil infusion was commenced 15 minutes before the procedure and discontinued 10 minutes after PICC securement and dressing application Dedicated nurses performed the procedure using polyurethane catheters with a 24G cannula (Premicath, Vygon, Aachen, Germany) |
PIPP | Safety: adverse events |
| Lago (49), 2008, Italy | N = 57 (3 infants did not receive interventions) Infants ≤32 weeks GA requiring PICC in the first 2 weeks of life Between-group design Single center NICU |
Infants with major congenital anomalies, perinatal asphyxia, severe intracerebral hemorrhage, neurological disorders, sepsis, concomitant infusions of other opioids, sedatives, or neuromuscular blockers | Remifentanil 0.03 µg/kg/minute IV infusion + sucrose 12% 0.3 mL PO and NNS (n = 27) or Dextrose 5% IV infusion + sucrose 12% 0.3 mL and NNS (n = 27) Remifentanil and dextrose infusion were initiated 15 minutes before the procedure and discontinued after PICC securement and dressing application Sucrose was administered with a pacifier 2 minutes before the procedure Neonatologists performed the procedure using polyurethane catheters with a 24G cannula (Premicath, Vygon, Aachen, Germany) |
PIPP, NIPS | Safety: adverse events Procedure outcomes: procedure success, number of attempts, procedure duration |
| Lemyre (50), 2006, Canada | N = 54 (1 infant did not complete the procedure) Infants ≥ 24 weeks GA with no skin burns or rash; for infants < 27 weeks GA, they had to be at least 48 hours old Between-group design Single center NICU |
Infants with immature skin, suspected or proven significant central nervous system anomalies, facial anomalies, hepatic or renal dysfunction, receipt of muscle relaxants within 12 hours of procedure, receipt of opioids or sedatives at the time procedure | Tetracaine 4% gel (Ametop®, Smith-Nephew) 1.1 g TOP + non-pharmacological interventions (n = 27) or Professional Care Lotion (Smith-Nephew) 1.1 g TOP + non-pharmacological interventions (n = 26) The active gel and placebo were applied 30 minutes before the procedure and covered with an occlusive dressing Non-pharmacological interventions of NNS, swaddling, and comforting were applied as appropriate for GA Dedicated PICC nurses performed the procedure using a 24G/1.9 F or 28G/1.2F cannula (L-Cath Peel Away System, Luther Medical Inc, Tustin, CA) |
PIPP, duration of cry | Safety: adverse events Procedure outcomes: procedure success, number of attempts |
| Taddio (51), 2006, Canada | N = 111 (4 infants did not complete the procedure) Mechanically ventilated preterm and term infants requiring PICC Between-group design Multicenter, 2 NICUs |
Infants with clinical seizures, skin disorders with skin lesions or disruptions in skin integrity, receipt of muscle relaxants or inotropes at the time of the procedure | Tetracaine 4% gel 0.5 g TOP + placebo IV (n = 41) or Placebo gel 0.5 g TOP + morphine 0.1 mg/kg IV (n = 38) or Tetracaine 4% gel 0.5 g TOP + morphine 0.1 mg/kg IV (n = 28) The active gel and placebo were applied 40–45 minutes before the procedure at 2 potential sites and covered with an occlusive dressing IV interventions were initiated 20 minutes after gel application and administered over 20 minutes Trained nurses, clinical nurse specialists-nurse practitioners, neonatology fellows or staff neonatologists performed the procedure using polyurethane catheters with a 24G cannula |
Brow bulge | Safety: adverse events Procedure outcomes: procedure success |
| Ballantyne (52), 2003, Canada | N = 51; Infants ≥ 27 weeks corrected GA with appropriate growth for their age and requiring non-urgent PICC placement Between-group design Single center NICU |
Infants with major congenital anomalies, neurologic impairment, physiologic stress at the time of procedure, non-intact skin, previous exposure to tetracaine, receipt of sedatives and/or analgesics within 12 hours of the procedure | Tetracaine 4% gel (Ametop®, Smith-Nephew) 1 g TOP + non-pharmacological interventions (n = 25) or Eucerin-plus cream 1 g TOP + non-pharmacological interventions (n = 26) The active gel and placebo were applied 30 minutes before the procedure and covered with an occlusive dressing Non-pharmacological interventions included NNS and swaddling Dedicated PICC nurses performed the procedure using a 24G/1.9 F (L-Cath Peel Away System, Luther Medical Inc, Tustin, CA) |
PIPP | Safety: adverse events |
GA = gestational age; IV = intravenous; IVH = intraventricular hemorrhage; NICU = neonatal intensive care unit; NIPS = neonatal infant pain scale; NNS = non-nutritive sucking; NSAID = non-steroidal anti-inflammatory drug; PDA = patent ductus arteriosus; PICC = peripheral insertion of central catheter; PIPP = premature infant pain profile; PO = by mouth; TOP = topically
Quality of studies and risk of bias
Assessment of risk of bias in each domain for the critical and important outcomes from the included studies are presented in Table 2. All included studies had an overall low risk of bias.
Table 2.
Assessment of risk of bias for critically important and important outcomes
| Outcome | Randomization process | Deviations from intended interventions | Missing outcome data | Outcome measurement | Selection of reported results | Overall risk of bias |
|---|---|---|---|---|---|---|
| Pain | ||||||
| Roofthooft (47) | Low | Low | Low | Low | Low | Low |
| Shin (48) | Low | Low | Low | Low | Low | Low |
| Lago (49) | Low | Low | Low | Low | Low | Low |
| Lemyre (50) | Low | Low | Low | Low | Low | Low |
| Taddio (51) | Low | Low | Low | Low | Low | Low |
| Ballantyne (52) | Low | Low | Low | Low | Low | Low |
| Procedure success | ||||||
| Lago (49) | Low | Low | Low | Low | Low | Low |
| Lemyre (50) | Low | Low | Low | Low | Low | Low |
| Taddio (51) | Low | Low | Low | Low | Low | Low |
| Number of attempts | ||||||
| Lago (49) | Low | Low | Low | Low | Low | Low |
| Lemyre (50) | Low | Low | Low | Low | Low | Low |
| Procedure duration | ||||||
| Lago (49) | Low | Low | Low | Low | Low | Low |
| Adverse events | ||||||
| Shin (48) | Low | Low | Low | Low | Low | Low |
| Lago (49) | Low | Low | Low | Low | Low | Low |
| Lemyre (50) | Low | Low | Low | Low | Low | Low |
| Taddio (51) | Low | Low | Low | Low | Low | Low |
| Ballantyne (52) | Low | Low | Low | Low | Low | Low |
Outcomes
Critically important outcomes: Pain
The results for critically important outcomes are presented in Table 3 and summarized below.
Table 3.
Results of critically important outcomes for different pharmacological interventions
| Outcomes (assessment tool) | Study author and year* | Number of studies | Effect size (95% CI)† |
|---|---|---|---|
| Opioids | |||
| Remifentanil versus control | |||
| Skin preparation pain (PIPP) | Lago 2008 | 1 | SMD −1.41 (−2.01, −0.81) |
| Acute pain (PIPP) | Lago 2008 | 1 | SMD −1.59 (−2.21, −0.97) |
| Skin preparation pain (NIPS) | Lago 2008 | 1 | SMD −0.8 (−1.36, −0.25) |
| Acute pain (NIPS) | Lago 2008 | 1 | SMD −1.21 (−1.79, −0.62) |
| Remifentanil (high vs. low dose) | |||
| Acute pain (change in PIPP) | Shin 2014 | 1 | SMD −0.45 (−1.62, 0.72) |
| Morphine versus tetracaine | |||
| Skin preparation pain (BB) | Taddio 2006 (1) | 1 | SMD −0.67 (−1.14, −0.02) |
| Acute pain (BB) | Taddio 2006 (1) | 1 | SMD −0.39 (−0.85, 0.07) |
| Recovery pain (BB) | Taddio 2006 (1) | 1 | SMD −0.47 (−0.94, −0.01) |
| Morphine + tetracaine versus tetracaine | |||
| Skin preparation phase (BB) | Taddio 2006 (2) | 1 | SMD −0.87 (−1.39, −0.34) |
| Acute pain (BB) | Taddio 2006 (2) | 1 | SMD −0.65 (−1.17, −0.13) |
| Recovery pain (BB) | Taddio 2006 (2) | 1 | SMD −0.35 (−0.85, 0.16) |
| Topical anesthetics | |||
| Tetracaine versus control | |||
| Acute pain (PIPP) | Lemyre 2006 Ballantyne 2003 |
2 | SMD −0.05 (−1.70, 1.59) |
| Overall procedural pain (PIPP) | Lemyre 2006 Ballantyne 2003 |
2 | SMD −0.19 (−2.07, 1.69) |
| Overall procedural pain (duration of cry, in seconds) | Lemyre 2006 | 1 | MD 205.25 (−510.67, 921.17) |
| Morphine + tetracaine versus morphine | |||
| Skin preparation pain (BB) | Taddio 2006 (3) | 1 | SMD −0.21 (−0.72, 0.31) |
| Acute pain (BB) | Taddio 2006 (3) | 1 | SMD −0.27 (−0.78, 0.25) |
| Recovery pain (BB) | Taddio 2006 (3) | 1 | SMD 0.14 (−0.37, 0.66) |
| Acetaminophen (three different doses) | |||
| Acute pain (PIPP) | Roofthooft 2017 (1) Roofthooft 2017 (2) Roofthooft 2017 (3) |
1 1 1 |
SMD −0.05 (−0.67, 0.57) SMD 0.23 (−0.40, 0.57) SMD 0.27 (−0.89, 0.35) |
| Overall procedural pain (COMFORTneo) | Roofthooft 2017 (1) Roofthooft 2017 (2) Roofthooft 2017 (3) |
1 1 1 |
SMD 0.46 (−0.17, 1.09) SMD 0.00 (−0.62, 0.62) SMD 0.47 (−0.16, 1.10) |
BB brow bulge; NIPS neonatal infant pain scale; PIPP premature infant pain profile.
*The study by Taddio 2006 is a three-arm study: 2006 (1) = morphine versus tetracaine; 2006 (2) = morphine + tetracaine versus tetracaine; 2006 (3) = morphine + tetracaine versus morphine. The study by Roofthooft 2017 is a three-arm study: 2017 (1) = acetaminophen 20 mg/kg versus acetaminophen 10 mg/kg; 2017 (2) = acetaminophen 20 mg/kg versus acetaminophen 15 mg/kg; 2017 (3) = acetaminophen 15 mg/kg versus acetaminophen 10 mg/kg.
†Results are presented as mean difference (MD) or standard mean difference (SMD) with 95% confidence interval (CI).
Opioids
Three studies that evaluated opioids are included and results based on the comparison groups are presented.
Remifentanil versus control
In the study by Lago et al., remifentanil was effective in reducing pain during the skin preparation (SMD −1.41 [95% CI −2.01, −0.81]; n = 54) and needle puncture (SMD −1.59 [95% CI −2.21, −0.97]; n = 54) phases as assessed by the premature infant pain profile (PIPP). Its effectiveness was also noted for reducing pain during the skin preparation (SMD −0.8 [95% CI −1.36, −0.25]; n = 54) and needle puncture (SMD −1.21 [95% CI −1.79, −0.62]; n = 54) phases when assessed by the neonatal infant pain scale (NIPS) (49). Both groups of participants in this study received sucrose 12% solution and non-nutritive sucking pre-procedure (49).
Remifentanil (high versus low dose)
No difference in the change in PIPP score (SMD −0.45 [95% CI −1.62, 0.72]; n = 12) was reported between needle puncture and baseline phases in the study by Shin et al. comparing remifentanil 0.25 μg/kg/minute to 0.1 μg/kg/minute (48).
Morphine versus tetracaine
Morphine was associated with a reduction in pain during the skin preparation (SMD −0.67 [95% CI −1.14, −0.02]; n = 73) and recovery (SMD −0.47 [95% CI −0.94, −0.01]; n = 73) phases but not during needle puncture phase (SMD −0.39 [95% CI −0.85, 0.07]; n = 73) when compared to tetracaine using brow bulge in the study by Taddio et al. (51).
Morphine + tetracaine versus tetracaine
In the study by Taddio et al., morphine + tetracaine was associated with reduction in pain during the skin preparation (SMD −0.87 [95% CI −1.39, −0.34]; n = 63) and needle puncture (SMD −0.65 [95% CI −1.17, −0.13]; n = 63) phases but not during the recovery phase (SMD −0.35 [95% CI −0.85, 0.16]; n = 63) as assessed by brow bulge when compared to tetracaine alone (51).
Clinical heterogeneity was observed in all three studies for methodology used (e.g., procedural details, operator performing the procedure and outcome assessment tools). In the study by Lago et al., all enrolled infants received 12% sucrose solution orally with non-nutritive sucking 2 minutes before the procedure while no co-interventions were provided in the other two studies. Regarding healthcare professionals performing the PICC placement procedure, in the study by Taddio et al., trained nurses, clinical nurse specialists-nurse practitioners, neonatology fellows or staff neonatologists performed the procedure, while neonatologists performed the procedure in the study by Lago et al. and dedicated nurses performed the procedure in the study by Shin et al. (48,49,51). In the study by Taddio et al., pain was assessed using a unidimensional behavioural measure (brow bulge) while in the other two studies, pain was assessed using a multidimensional measure (PIPP or NIPS) (48,49,51).
Topical anesthetics
Tetracaine versus control
There was no difference in pain during the needle puncture (SMD −0.05 [95% CI −1.70, 1.59], I2 = 0%; n = 98) phase or for the overall procedural pain score (SMD −0.19 [95% CI −2.07, 1.69], I2 = 0%; n = 100) comparing tetracaine to control as assessed by the PIPP scale in the studies by Lemyre et al. and Ballantyne et al. (50,52) Additionally, in the study by Lemyre et al., the duration of cry (seconds) during the overall procedure was not significantly different (MD 205.25 [95% CI −510.67, 921.17]; n = 15) (50).
Morphine + tetracaine versus morphine
In the study by Taddio et al., there was no significant difference in pain as assessed by brow bulge for the skin preparation (SMD −0.21 [95% CI −0.72, 0.31]; n = 60), needle puncture (SMD −0.27 [95% CI −0.78, 0.25]; n = 60) or recovery (SMD 0.14 [95% CI −0.37, 0.66]; n = 60) phases when morphine + tetracaine was compared to morphine alone (51).
Topical tetracaine was applied 40–45 minutes before the PICC placement in the study by Taddio et al. while it was applied 30 minutes before the procedure in the studies by Lemyre et al. and Ballantyne al (50–52). Non-pharmacological interventions of non-nutritive sucking, swaddling and comforting were only used in the studies by Lemyre et al. and Ballantyne et al. (50,52). Dedicated nurses performed the procedure in the studies by Lemyre et al. and Ballantyne et al. (50,52).
Acetaminophen (three different doses)
There was no significant difference in the PIPP or COMFORTneo scores for needle puncture and overall procedure pain when three doses of acetaminophen were compared in the study by Roofthooft et al. Experienced nurse practitioners or neonatologists performed PICC placements in this study (47).
Important outcomes: Procedure outcomes and safety
Summary statistics and effect estimates for important outcomes are presented in Table 4 and described below.
Table 4.
Results of important outcomes for different pharmacological interventions
| Outcomes | Study author and year* | Number of studies | Effect size (95% CI)† |
|---|---|---|---|
| Opioids | |||
| Remifentanil versus control | |||
| Procedure success | Lago 2008 | 1 | RR 1.25 (0.85, 1.84) |
| Procedure duration, in minutes | Lago 2008 | 1 | MD 4 (−3.74, 11.74) |
| Number of attempts | Lago 2008 | 1 | MD 0.3 (−0.15, 0.75) |
| Morphine versus tetracaine | |||
| Procedure success | Taddio 2006 (1) | 1 | RR 0.94 (0.54, 1.66) |
| Morphine + tetracaine versus tetracaine | |||
| Procedure success | Taddio 2006 (2) | 1 | RR 0.92 (0.49, 1.71) |
| Topical anesthetics | |||
| Tetracaine versus control | |||
| Procedure success | Lemyre 2006 | 1 | RR 0.79 (0.61, 1.03) |
| Number of attempts | Lemyre 2006 | 1 | MD 0.07 (−1.02, 1.16) |
| Morphine + tetracaine versus morphine | |||
| Procedure success | Taddio 2006 (3) | 1 | RR 0.97 (0.51, 1.85) |
*The study by Taddio 2006 is a three-arm study: 2006 (1) = morphine versus tetracaine; 2006 (2) = morphine + tetracaine versus tetracaine; 2006 (3) = morphine + tetracaine versus morphine.
†Results are presented as relative risk (RR) as mean difference (MD) with 95% confidence interval (CI).
2.1 Procedure outcomes
Opioids
There was no difference in the outcomes of procedure success, procedure duration and number of attempts when remifentanil was compared to control in the study by Lago et al. (49). Similarly, there was no difference in procedure success when morphine was compared to tetracaine alone or for the comparison of morphine + tetracaine with tetracaine in the study by Taddio et al. (51). Procedural outcomes were not assessed in the study by Shin et al. (48).
Topical anesthetics
In the study by Lemyre et al., no difference in the outcomes of procedure success and number of attempts were observed when tetracaine was compared to control (50). Similarly, there was no difference in procedure success when morphine + tetracaine was compared to morphine alone in the study by Taddio et al. (51). The study by Ballantyne et al. did not assess procedural outcomes (52).
Acetaminophen (three different doses)
No procedural outcomes were assessed for acetaminophen in the study by Roofthooft et al. (49).
2.2 Safety
Opioids
No episodes of hypotension needing intervention, apnea, bradycardia or chest wall rigidity were reported during and after remifentanil or placebo infusions in the study by Lago et al. Six and four neonates in the remifentanil and control groups respectively required increase in oxygen concentration due to significant desaturation (49).
Sixty-six neonates who received IV morphine alone or IV morphine + topical tetracaine were compared to 41 neonates who received topical tetracaine in the study by Taddio et al. (51) No difference in mean blood pressure in the first hour after IV morphine administration was reported. Hypotension was reported in three neonates in the IV morphine group compared to no hypotensive episodes in the topical tetracaine group. An increase in ventilation rate in the first 12 hours was noted in neonates receiving IV morphine compared to topical tetracaine in a subgroup of neonates who were intubated and mechanically ventilated (P = 0.003) (51).
Three neonates experienced apneic events in the high-dose remifentanil group (with one of three also experiencing bradycardia after apnea) compared to no neonates who received the low-dose remifentanil group in the study by Shin et al. All neonates were mechanically ventilated and adverse events were managed (48).
Topical anesthetics
Transient skin erythema was noted in three and one neonates in the topical tetracaine and control groups respectively in the study by Lemyre et al. (50). Sustained bradycardia (heart rate 80 beats/minute) was reported in one neonate in the topical tetracaine group, with no episodes of desaturation or hypotension following insertion of a nasogastric tube while the tetracaine was applied on the skin. The PICC placement was postponed, and the neonate recovered after 45 minutes. Laboratory parameters of complete blood count, alanine transaminase, and creatinine were similar in both groups (50). No adverse events were reported in the study by Ballantyne et al. study (52).
Of the 69 neonates treated with topical tetracaine alone or morphine + topical tetracaine, 21 (30%) neonates developed erythema at the application site compared to none of the 38 neonates treated with morphine alone in the 2006 study by Taddio et al. (51) A severe skin reaction was reported in one neonate who developed erythema followed by blistering and desquamation and bradycardia (ultimately attributed to an unrelated pneumothorax) within 10 minutes of tetracaine application. The skin healed within a week with no long-term consequences (51).
Acetaminophen (three different doses)
No adverse events were recorded in the study by Roofthooft et al. (47).
Certainty of evidence
The GRADE summary of findings tables for opioids, topical anesthetics and acetaminophen are presented in Tables 5–7. There was moderate certainty of evidence for all critical and important outcomes in all intervention categories. All outcomes were subject to serious inconsistency due to imprecision as the sample size was below the recommended optimal information size.
Table 5.
GRADE evidence profile for opioids
| Certainty assessment | No. of patients | Effect | Certainty | Importance | ||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| No. of studies | Study design | Risk of bias | Inconsistency | Indirectness | Imprecision | Other | Opioid | Comparison | Relative (95% CI) | Absolute (95% CI) | ||
| Remifentanil versus control | ||||||||||||
| Outcome: Skin preparation pain (PIPP) | ||||||||||||
| 1 | RCT | Not serious | Not serious | Not serious | Serious* | None | 27 | 27 | - | SMD −1.41 (−2.01, −0.81) | Moderate | Critical |
| Outcome: Acute pain (PIPP) | ||||||||||||
| 1 | RCT | Not serious | Not serious | Not serious | Serious* | None | 27 | 27 | - | SMD −1.59 (−2.21, −0.97) | Moderate | Critical |
| Outcome: Skin preparation pain (NIPS) | ||||||||||||
| 1 | RCT | Not serious | Not serious | Not serious | Serious* | None | 27 | 27 | - | SMD −0.80 (−1.36, −0.25) | Moderate | Critical |
| Outcome: Acute pain (NIPS) | ||||||||||||
| 1 | RCT | Not serious | Not serious | Not serious | Serious* | None | 27 | 27 | - | SMD −1.21 (−1.79, −0.62) | Moderate | Critical |
| Outcome: Procedure success | ||||||||||||
| 1 | RCT | Not serious | Not serious | Not serious | Serious* | None | 27 | 27 | RR 1.25 (0.85, 1.84) | - | Moderate | Important |
| Outcome: Procedure duration | ||||||||||||
| 1 | RCT | Not serious | Not serious | Not serious | Serious* | None | 27 | 27 | - | MD 4 (−3.74, 11.74) | Moderate | Important |
| Outcome: Number of attempts | ||||||||||||
| 1 | RCT | Not serious | Not serious | Not serious | Serious* | None | 27 | 27 | - | MD 0.3 (−0.15, 0.75) | Moderate | Important |
| Remifentanil (high vs. low dose) | ||||||||||||
| Outcome: Acute pain (Change in PIPP) | ||||||||||||
| 1 | RCT | Not serious | Not serious | Not serious | Serious* | None | 7 | 5 | - | SMD −0.45 (−1.62, 0.72) | Moderate | Critical |
| Morphine versus tetracaine | ||||||||||||
| Outcome: Skin preparation pain (BB) | ||||||||||||
| 1 | RCT | Not serious | Not serious | Not serious | Serious* | None | 35 | 38 | - | SMD −0.67 (−1.14, −0.02) | Moderate | Critical |
| Outcome: Acute pain (BB) | ||||||||||||
| 1 | RCT | Not serious | Not serious | Not serious | Serious* | None | 35 | 38 | - | SMD −0.39 (−0.85, 0.07) | Moderate | Critical |
| Outcome: Recovery pain (BB) | ||||||||||||
| 1 | RCT | Not serious | Not serious | Not serious | Serious* | None | 35 | 38 | - | SMD −0.47 (−0.94, −0.01) | Moderate | Critical |
| Outcome: Procedure success | ||||||||||||
| 1 | RCT | Not serious | Not serious | Not serious | Serious* | None | 38 | 41 | RR 0.94 (0.54, 1.66) | - | Moderate | Important |
| Morphine + tetracaine versus tetracaine | ||||||||||||
| Outcome: Skin preparation pain (BB) | ||||||||||||
| 1 | RCT | Not serious | Not serious | Not serious | Serious* | None | 25 | 38 | - | SMD −0.87 (−1.39, −0.34) | Moderate | Critical |
| Outcome: Acute pain (BB) | ||||||||||||
| 1 | RCT | Not serious | Not serious | Not serious | Serious* | None | 25 | 38 | - | SMD −0.65 (−1.17, −0.13) | Moderate | Critical |
| Outcome: Recovery pain (BB) | ||||||||||||
| 1 | RCT | Not serious | Not serious | Not serious | Serious* | None | 25 | 38 | - | SMD −0.35 (−0.85, 0.16) | Moderate | Critical |
| Outcome: Procedure success | ||||||||||||
| 1 | RCT | Not serious | Not serious | Not serious | Serious* | None | 28 | 41 | RR 0.92 (0.49, 1.71) | - | Moderate | Important |
BB = brow bulge; CI = confidence interval, MD = mean difference; No. = number; NIPS = neonatal infant pain scale; PIPP = premature infant pain profile; RCT = randomized controlled trial; RR = relative risk.
*Sample size below the recommended optimal information size
Table 7.
GRADE evidence profile for acetaminophen
| Certainty assessment | No. of patients | Effect | Certainty | Importance | ||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| No. of studies | Study design | Risk of bias | Inconsistency | Indirectness | Imprecision | Other | Dose 1 | Dose 2 | Relative (95% CI) | Absolute (95% CI) | ||
| Acetaminophen 20 mg/kg versus acetaminophen 10 mg/kg | ||||||||||||
| Outcome: Acute pain (PIPP) | ||||||||||||
| 1 | RCT | Not serious | Not serious | Not serious | Serious* | None | 20 | 20 | - | SMD −0.05 (−0.67, 0.57) | Moderate | Critical |
| Outcome: Overall procedural pain (COMFORTneo) | ||||||||||||
| 1 | RCT | Not serious | Not serious | Not serious | Serious* | None | 20 | 20 | - | SMD 0.46 (−0.17, 1.09) | Moderate | Critical |
| Acetaminophen 20 mg/kg versus acetaminophen 15 mg/kg | ||||||||||||
| Outcome: Acute pain (PIPP) | ||||||||||||
| 1 | RCT | Not serious | Not serious | Not serious | Serious* | None | 20 | 20 | - | SMD 0.23 (−0.40, 0.57) | Moderate | Critical |
| Outcome: Overall procedural pain (COMFORTneo) | ||||||||||||
| 1 | RCT | Not serious | Not serious | Not serious | Serious* | None | 20 | 20 | - | SMD 0.00 (−0.62, 0.62) | Moderate | Critical |
| Acetaminophen 15 mg/kg versus acetaminophen 10 mg/kg | ||||||||||||
| Outcome: Acute pain (PIPP) | ||||||||||||
| 1 | RCT | Not serious | Not serious | Not serious | Serious* | None | 20 | 20 | - | SMD 0.27 (−0.89, 0.35) | Moderate | Critical |
| Outcome: Overall procedural pain (COMFORTneo) | ||||||||||||
| 1 | RCT | Not serious | Not serious | Not serious | Serious* | None | 20 | 20 | - | SMD 0.47 (−0.16, 1.1) | Moderate | Critical |
CI confidence interval; No. number; PIPP premature infant pain scale; RCT randomized controlled trial; SMD standardized mean difference.
*Sample size below the recommended optimal information size
Table 6.
GRADE evidence profile for topical anesthetics
| Certainty assessment | No. of patients | Effect | Certainty | Importance | ||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| No. of studies | Study design | Risk of bias | Inconsistency | Indirectness | Imprecision | Other | Topical anesthetic | Comparison | Relative (95% CI) | Absolute (95% CI) | ||
| Tetracaine versus control | ||||||||||||
| Outcome: Acute pain (PIPP) | ||||||||||||
| 2 | RCT | Not serious | Not serious | Not serious | Serious* | None | 49 | 49 | - | SMD −0.05 (−1.70, 1.59) | Moderate | Critical |
| Outcome: Overall procedural pain (PIPP) | ||||||||||||
| 2 | RCT | Not serious | Not serious | Not serious | Serious* | None | 51 | 49 | - | SMD −0.19 (−2.07, 1.69) | Moderate | Critical |
| Outcome: Overall procedural pain (Duration of cry) | ||||||||||||
| 1 | RCT | Not serious | Not serious | Not serious | Serious* | None | 7 | 8 | - | MD 205.25 (−510.67, 921.17) | Moderate | Critical |
| Outcome: Procedure success | ||||||||||||
| 1 | RCT | Not serious | Not serious | Not serious | Serious* | None | 26 | 26 | RR 0.79 (0.61, 1.03) | - | Moderate | Important |
| Outcome: Number of attempts | ||||||||||||
| 1 | RCT | Not serious | Not serious | Not serious | Serious* | None | 26 | 26 | - | MD 0.07 (−1.02, 1.16) | Moderate | Important |
| Morphine + tetracaine versus morphine | ||||||||||||
| Outcome: Skin preparation pain (BB) | ||||||||||||
| 1 | RCT | Not serious | Not serious | Not serious | Serious* | None | 25 | 35 | - | SMD −0.21 (−0.72, 0.31) | Moderate | Critical |
| Outcome: Acute pain (BB) | ||||||||||||
| 1 | RCT | Not serious | Not serious | Not serious | Serious* | None | 25 | 35 | - | SMD −0.27 (−0.78, 0.25) | Moderate | Critical |
| Outcome: Recovery pain (BB) | ||||||||||||
| 1 | RCT | Not serious | Not serious | Not serious | Serious* | None | 25 | 35 | - | SMD 0.14 (−0.37, 0.66) | Moderate | Critical |
| Outcome: Procedure success | ||||||||||||
| 1 | RCT | Not serious | Not serious | Not serious | Serious* | None | 28 | 38 | RR 0.97 (0.51, 1.85) | - | Moderate | Important |
BB = brow bulge; CI = confidence interval; MD = mean difference; No. = number; PIPP = premature infant pain scale; RCT = randomized controlled trial; RR = relative risk; SMD = standardized mean difference.
*Sample size below the recommended optimal information size
DISCUSSION
In this systematic review and meta-analysis, the effectiveness of various pain management interventions for PICC placement was evaluated. The interventions included IV opioids (morphine, remifentanil), topical anesthetics (tetracaine) and IV acetaminophen. Opioids were the only pharmacological intervention with evidence of effectiveness in reducing pain from PICC placement (49,51). It is important to note that Taddio et al. included a non-randomized group without analgesia when the RCT was underway. They demonstrated that compared to the no-treatment group, pain scores were lower in the morphine and morphine + tetracaine groups during skin preparation and needle puncture phases while pain scores were not different when compared to the tetracaine alone group, further confirming the benefits of opioids (51). Despite its effectiveness, opioid use is associated with adverse events including respiratory depression, increased need for ventilatory support and hypotension. One study included mechanically ventilated infants while two studies included infants both on mechanical and non-invasive ventilation (48,49,51). In terms of topical anesthetics, tetracaine showed no analgesic benefit (50–52), and in a single study evaluating three different doses of IV acetaminophen, no difference in pain scores was noted (47). In regard to important outcomes, there was no difference in procedure success, procedure duration and number of attempts when opioids and topical anesthetics were evaluated.
In neonates, opioids are the mainstay for analgesia in the management of moderate to severe painful procedures such as PICC placement and their use has been recommended in national and international guidelines (14,15). The most frequently used opioids are morphine and fentanyl, which are typically administered via the IV route. The analgesic effect of opioids is mediated via the µ receptor, although they can also act on the Κ-opioid receptor subtypes (53). However, opioid use may be associated with respiratory depression, hypotension and, potentially, chest wall rigidity. As such, clinicians must consider their risk-benefit profile when prescribed for procedural analgesia in neonates.
Recently, intranasal (IN) administration has emerged as an alternative route to achieve rapid drug delivery and retrospective studies have reported benefits of IN fentanyl for procedural pain from lumbar puncture, PICC placement and endotracheal intubation (54,55). Two RCTs demonstrated the benefit of IN fentanyl for retinopathy of prematurity screening (56,57). In a recent systematic review, Snyers et al. examined multiple IN pharmacological agents (midazolam, fentanyl, ketamine, dexmedetomidine) for various painful procedures. Across studies, there was a reduction in pain and sedation markers, and adverse events were infrequent and not significant (e.g., apnea, desaturation, hypotension) (58). IN analgosedatives are potential pharmacological alternatives that should be evaluated in future RCTs for pain management during PICC placement (54–58).
Other non-pharmacological interventions that could potentially have a synergistic effect with opioids include the use of sweetening agents (e.g., sucrose) and non-nutritive sucking. In the study by Roofthooft et al., a non-randomized group of neonates received 24% oral sucrose (0.5 mL for neonates < 1 kg and 1 mL for neonates ≥ 1 kg) for the PICC placement. Pain scores were comparable between acetaminophen and sucrose groups, but the study was not designed to evaluate the effectiveness of sucrose as there was no control group (47). In the study by Lago et al., all randomized neonates received 12% sucrose and non-nutritive sucking in addition to study interventions; however, the additive effect of non-pharmacological interventions could not be assessed (49). Other procedural characteristics that could be optimized include the use of ultrasound guidance for PICC placement. A 2020 study by Sabouneh et al. reported less pain, higher success rate, shorter procedure duration, and reduced number of attempts for ultrasound-guided placement compared to PICC placement without ultrasound guidance (59).
This systematic review and meta-analysis has limitations. First is the inclusion of a number of studies with relatively small sample sizes for the interventions being evaluated. Second, half of the included studies did not have a control group (placebo or no treatment) which limits the ability for causal inference. Of note, researchers may have excluded a control group to prevent neonates from experiencing iatrogenic pain unnecessarily.
In conclusion, there is moderate evidence to recommend opioids as part of the armamentarium for PICC placement. Studies evaluating other opioids and non-opioids as analgesics delivered in combination with non-pharmacological interventions should be explored.
Appendix 1. Search strategy
Database: Embase Classic+. Dates: 1947 to 2024 March 22
| # | Searches | Comment |
|---|---|---|
| 1 | pain assessment/ or pain/ or application site pain/ or arm pain/ or injection pain/ or injection site pain/ or nociceptive pain/ or psychogenic pain/ or skin pain/ or nociception/ or perceptive threshold/ or pain threshold/ or pressure pain threshold/ | |
| 2 | (pain or pains or pained or painful* or distress* or nociception or nociperception).ti,ab,kf. | |
| 3 | Visual analog scale/ or (instrument* or scale* or assess* or measure* or degree* or score* or scoring).ti,ab,kf. | |
| 4 | breast milk/ or ((breast or hind or mother* or maternal*) adj2 milk).ti,ab,kf. or hindmilk.ti,ab,kf. | |
| 5 | breastfeeding/ or breast milk expression/ or (breastfeeding or breastfed or “breast-feeding”).ti,ab,kf. | |
| 6 | Pacifier/ or (“non-nutritive suck*” or “non lactating nipple*” or “non-lactating nipple*” or pacifier* or pacifying).ti,ab,kf. | |
| 7 | artificial milk/ or ((baby or infan* or feeding or milk) adj2 formula*).ti,ab,kf. | |
| 8 | sucrose/ or (sucrose or glucose or saccharose or ((cane or beet) adj2 sugar*) or microtal or “saccharum album” or tabfine).ti,ab,kf. | |
| 9 | exp sweetening agent/ or (sweetener* or sweetening or sugar*).ti,ab,kf. | |
| 10 | Kangaroo Care/ or bed sharing/ or (swaddl* or (facilitat* adj2 tuck*) or “skin to skin” or “skin-to-skin” or (kangaroo adj2 care) or “co-bedding” or “co bedding” or (bed adj2 shar*)).ti,ab,kf. | |
| 11 | body position/ or position/ or body posture/ or recumbency/ or supine position/ | |
| 12 | (positioning or positions or positioned or containment or containing).ti,ab,kf. | |
| 13 | (rocking or holding or swinging or cuddling).ti,ab,kf. | |
| 14 | (rubbing or talking or shushing or comforting).ti,ab,kf. | |
| 15 | “cluster* of procedure*.”ti,ab,kf. | |
| 16 | Sucking/ or (sucking or suck or sucks or sucked).ti,ab,kf. | |
| 17 | heating/ or environmental temperature/ or room temperature/ or brightness/ or darkness/ or glare/ or illumination/ or light exposure/ or light intensity/ or light stress/ or (ventilation or warming).ti,ab,kf. | |
| 18 | local anesthesia/ or topical anesthesia/ or exp local anesthetic agent/ | |
| 19 | acetaminophen/ or (“a-mol” or abenol or acamol or acenol or acephen or acetalgin or “acetamino phenol” or acetaminophen* or acetamol or acetomenophen or acetylaminophenol or adorem or afebrin or algiafin or algocit or algotropyl or alphagesic or alvedon or amadil or “anacin 3” or anaflon or analgiser or apamide or apap or apirex or apotel or arthralgen or atamel or “ben-u-ron” or benuron or biogesic or bodrex or calapol or calodol or calonal or calpol or causalon or cemol or christamol or claradol or clocephen or “cp 500” or cp500 or dafalgan or daga or datril or depon or depyretin or dirox or dismifen or disprol or dolal or dolex or doliprane or dolitabs or dolofen or dolomol or dolorol or dolotemp or dolprone or doltem or drilan or duorol or dymadon or efferalgan or efferalganodis or efferelgan or enelfa or eneril or eraldor or exopon or expandol or febrilix or fendon or fervex or fibrinol or fortolin or gelocatil or “geluprane 500” or gunaceta or hedex or helporal or “infants’ feverall” or injectapap or janupap or kamolas or kyofen or lekadol or lemgrip or letamol or liquiprin or lotemp or lyteca or malidens or medamol or meforagesic or metagesic or metalid or mexalen or “milidon 500” or minopan or mypara or nalgesik or napamol or napap or naprex or nebs or “nektol 500” or neodalmin or neopap or nevral or nilapur or nobedon or nysacetol or ofirmev or pacemol or pacimol or pamal or pamol or panadol or panamax or panasorb or panodil or paracet or paracetaminophenol or paracetamol* or parageniol or paragin or paralen or paralief or paramax or paramidol or parapaed or paratabs or parvid or pasolind or paximol or pedipan or perfalgan or phenaphen or pinex or polarfen or predimol or puernol or pyrigesic or raperon or rapidol or relaphen or reliv or remedol or revanin or rhodapap or salzone or serimol or setamol or sinaspril or sinedol or sinpro or supofen or tabalgin or tachipirin* or taganopain or tapar or tempra or tempte or temzzard or termofren or tralgon or tramil or treuphadol or turpan or tylenol or tylex or valadol or winadol or winasorb or xebramol or zolben or zydinol).mp. or 103-90-2.rn. | |
| 20 | ibuprofen/ or (“act-3” or “adex 200” or advil or afebril or aktren or algifor or algofen or algoflex or allipen or “am-fam 400” or anadvil or analgyl or anbifen or anco or andran or anflagen or antarene or antiflam or ibuprofen or “atril 300” or attritin or balkaprofen or bestafen or betaprofen or bifen or bluton or brufanic or brufen or brufort or brugesic or brumed or buburone or bufect or bufohexal or bupogesic or burana or butacortelone or caldolor or “cap-profen” or cenbufen or motrin or combiflam or contraneural or cuprofen or “dc 7034” or dc7034 or “dg 7034” or dg7034 or dibufen or “dolan fp” or dolgit or dolocyl or dolodolgit or “dolofen-f” or dolomax or dolormin or dolval or “donjust b” or dorival or druisel or easifon or ecoprofen or emflam or epobron or exidol or expanfen or febratic or febryn or femapirin or fenalgic or fenbid or flamicon or “h-loniten” or halprin or haltran or “ib-100” or ibofen or ibosure or ibu or ibuberl or ibudak or ibufen or ibuflam or ibufug or ibugel or ibugesic or ibulgan or ibuloid or ibumetin or ibupen or ibupirac or ibuprin or ibuprocin or ibuprofen or “klinge 600” or ibuprofene or ibuprohm or iburon or ibusal or ibustar or ibusynth or ibutop or “idyl sr” or infibu or ipren or irfen or isdol or isodol or junifen or kontraneural or lamidon or librofem or lidifen or liptan or lopane or malafene or maxagesic or “mcn r 1451” or medicol or medipren or mediprin or mensoton or motrin or mynosedin or “nagifen-d” or napacetin or neobrufen or nerofen or neutropain or nobfelon or nobgen or “norflam-t” or noritis or norton or novogent or novoprofen or nugin or nuprin or nureflex or nurofen or ostarin or ostofen or paduden or panafen or pedea or perofen or proartinal or profen or profeno or proflex or proris or provon or quadrax or rafen or ranofen or rebugen or renidon or reuvol or rhelafen or roidenin or rufen or rupan or schufen or seclodin or “solufen lidose” or spedifen or spifen or syntofene or tabalon or taskine or tatanal or tofen or trendar or umafen or unipro or upfen or uprofen or urem or zofen).mp. or (15687-27-1 or 31121-93-4 or 527688-20-6 or 79261-49-7).rn. | |
| 21 | short acting analgesic agent/ or ((“short acting” or “short-acting”) adj2 analgesic*).mp. | |
| 22 | Conscious Sedation/ or ((conscious or moderate) adj2 sedat*).ti,ab,kf. | |
| 23 | narcotic agent/ or narcotic analgesic agent/ or (narcotic or narcotics or stupefacient).mp. | |
| 24 | alfentanil/ or (alfenil or alfenta or “alfentanil hydrochloride” or alfentanyl or brevafen or fanaxal or fentalim or “r 39,209” or “r 39209” or rapifen).mp. or (69049-06-5 or 71195-58-9).rn. | |
| 25 | dihydromorphine/ or (dihydromorphine or hydromorphine or paramorphan).mp. or (1421-28-9 or 509-60-4).rn. | |
| 26 | ethylmorphine/ or (codethyline or diolan or dionine or “ethyl morphine” or ethylmorfine or ethylmorphin or “morphine ethyl ether”).mp. or (125-30-4 or 76-58-4).rn. | |
| 27 | fentanyl/ or (abstral or “ap 48” or ap48 or duragesic or fentamyl or fentanil or fentanyl or fetnanyl or instanyl or ionsys or lazanda or leptanal or onsolis or pecfent or phentanyl or “r 4263” or r4263 or rapinyl or recuvyra or subsys or tanyl or transfenta).mp. or 437-38-7.rn. | |
| 28 | morphine/ or (anpec or morphine or duromorph or epimorph or miro or morfin or morfine or morphia or morphin or morphine or morphinium or morphium or opso or skenan).mp. or (52-26-6 or 57-27-2).rn. | |
| 29 | sufentanil/ or (“arx 01” or arx01 or fentathianyl or fentathienyl or fentatienil or “r 30,730” or “r 30730” or “r30,730” or r30730 or sufentanyl or sulfentanil or sulfentanyl or zalviso).mp. or 56030-54-7.rn. | |
| 30 | exp analgesic agent/ or ((“non narcotic” or “non-narcotic”) adj2 (analgesic* or analgetic*)).mp. | |
| 31 | topical drug administration/ or ((local or topic or topical*) adj3 (administration* or administer* or analges* or delivery or dose* or dosage* or instillation* or infusion* or inject* or medication or treatment* or therap*)).ti,ab,kf. | |
| 32 | (vapo-coolant* or vapocoolant*).ti,ab,kf. | |
| 33 | (therapeutic adj2 touch).ti,ab,kf. or art therapy/ or (sensory adj2 art adj2 therap*).ti,ab,kf. or music therapy/ or speleotherapy/ or speleotherap*.ti,ab,kf. | |
| 34 | Music/ or music.ti,ab,kf. | |
| 35 | Emotion/ or (emotion* adj2 (factor* or response* or status or express*)).ti,ab,kf. or fear/ or anxiety/ or (fear* or anxiet* or anxious*).ti,ab,kf. or pleasure/ or “smelling and taste”/ or aroma/ or odor/ or (pleasure* or aroma* or odors or odor or odour* or scent* or smell*).ti,ab,kf. or olfactory discrimination/ or (odor* or odour* or smell* or (discriminat* or acuity or sensitivity)).ti,ab,kf. or olfactory memory/ or (olfactory adj2 memor*).ti,ab,kf. or smelling/ or (olfaction or olfactory).ti,ab,kf. or taste/ or (gustation or gustatory or taste or tasting).ti,ab,kf. or touch/ or (haptic or tactile or touch or tactual).ti,ab,kf. or tactile discrimination/ or tactile memory/ or tactile stimulation/ or vibration sense/ or ((vibrating or vibration) adj2 (sense or perception or sensation or sensitivity)).ti,ab,kf. or voice/ or voice.ti,ab,kf. or sound/ or sound*.ti,ab,kf. | |
| 36 | Facial Expression/ or Gesture/ or ((facial adj5 express*) or grimace* or grimacing or discomfort* or gesture*).ti,ab,kf. | |
| 37 | crying/ or (crying or cries or cry or weeping).ti,ab,kf. | |
| 38 | attitude/ or attitude to health/ or attitude to illness/ or health personnel attitude/ or nurse attitude/ or physician attitude/ or (“professional-family relation*” or (professional adj2 family adj2 relation*)).ti,ab,kf. | |
| 39 | family attitude/ or maternal attitude/ or parental attitude/ or paternal attitude/ or parental behavior/ or maternal behavior/ or paternal behavior/ or child parent relation/ or father child relation/ or mother child relation/ | |
| 40 | exp parent/ or ((Parent* or mother* or maternal* or paternal or father*) adj2 (presen* or coaching or training or educat*)).ti,ab,kf. | |
| 41 | mental stress/ or ((mental or psychologic* or nervous or psychic) adj2 (stress* or tension)).ti,ab,kf. | |
| 42 | physiological stress/ or ((biologic* or physiologic* or organismal) adj2 stress*).ti,ab. or oxidative stress/ or ((oxidant or oxidative*) adj2 stress*).ti,ab,kf. | |
| 43 | heart rate/ or “heart rate and rhythm”/ or heart rate variability/ or resting heart rate/ or ((heart adj2 rate*) or “beat to beat variab*” or “beat-to-beat variab*”).ti,ab,kf. | |
| 44 | exp blood pressure/ or ((blood adj2 pressure) or hypertensi* or hypotensi*).ti,ab,kf. | |
| 45 | transcutaneous oxygen monitoring/ or ((Transcutaneous adj3 monitor*) or tcpo2 or tcpco2).ti,ab,kf. | |
| 46 | oximetry/ or hypoxia/ or (oximetr* or hypoxia or hypoxic).ti,ab,kf. | |
| 47 | or/1-46 | Pain measurement or intervention terms |
| 48 | limit 47 to infant < to one year> | |
| 49 | infant/ or low birth weight/ or small for date infant/ or very low birth weight/ or very low birth weight/ or extremely low birth weight/ or postmaturity/ or prematurity/ | |
| 50 | Neonatology/ or newborn intensive care nursing/ or newborn intensive care/ | |
| 51 | (newborn* or “new-born*” or baby* or babies or neonat* or perinat* or postmatur* or postnat* or “peri-nat*” or “post-nat*” or preemie* or prematur* or “pre-mature” or “pre-term” or prematuritas or preterm or “low birth weight” or “low birth-weight” or “low birthweight” or underweight LBW or ELBW or “small for gestational age” or “small for date” or VLBW or NICU*).mp. | |
| 52 | or/49-51 | Neonatal terms |
| 53 | 48 or (47 and 52) | Age group and interventions results |
| 54 | central venous catheterization/ or vein catheterization/ or subclavian vein catheterization/ | |
| 55 | ((central or venous) adj3 catheter*).ti,ab. | |
| 56 | catheter/ and ((“in-dwelling” or indwelling or implantable) adj3 catheter*).ti,ab. | |
| 57 | vascular access device/ | |
| 58 | central venous catheter/ or peripherally inserted central venous catheter/ or subclavian vein catheter/ | |
| 59 | ((arterial* or “intra-arterial*” or central* or vascular or venous) adj3 (access or line or lines or catheter* or device* or placed* or port or reservoir*)).ti,ab. | |
| 60 | (venous adj3 (cannual* or canula* or catheter* or administration* or administer* or applicat* or delivery or dose* or dosage* or instillation* or infusion* or inject* or medication or treatment* or therap* or punctur* or poke or pokes or tap or taps or prick*)).ti,ab,kf. | |
| 61 | cannula/ and venous.ti,ab. | |
| 62 | (venous adj3 (cannula* or canula* or catheter* or administration* or administer* or applicat* or delivery or dose* or dosage* or instillation* or infusion* or inject* or medication or treatment* or therap* or punctur* or poke or pokes or tap or taps or tapping or tapped or prick*)).ti,ab. | |
| 63 | Seldinger*.ti,ab. | |
| 64 | peripherally inserted central venous catheter/ or ((picc or peripheral*) adj3 (catheter* or insert* or line or lines or placement*)).ti,ab. | |
| 65 | (needle/ or syringe needle/ or syringe/ or catheter/) and (size or sizes or sizing or gauge* or guage*).ti,ab. | |
| 66 | or/54-65 [****Venous access****] | PICC terms |
| 67 | 53 and 66 [***Spinal tap results****] | PICC results |
| 68 | limit 67 to human | |
| 69 | (human or humans or patient*).ti,ab,kf. | |
| 70 | 68 or (67 and 69) | Limit to humans |
| 71 | randomized controlled trial/ | |
| 72 | Controlled clinical study/ | |
| 73 | random*.ti,ab. | |
| 74 | Randomization/ | |
| 75 | Intermethod comparison/ | |
| 76 | placebo*.ti,ab. | |
| 77 | (compare or compared or comparison).ti. | |
| 78 | ((evaluated or evaluate or evaluating or assessed or assess) and (compare or compared or comparing or comparison)).ab. | |
| 79 | (open adj label).ti,ab. | |
| 80 | ((double or single or doubly or singly) adj (blind or blinded or blindly)).ti,ab. | |
| 81 | double-blind procedure/ | |
| 82 | Parallel group$1.ti,ab. | |
| 83 | (Crossover or cross over).ti,ab. | |
| 84 | ((assign* or match or matched or allocation) adj5 (alternate or group$1 or intervention$1 or patient$1 or subject$1 or participant$1)).ti,ab. | |
| 85 | (assigned or allocated).ti,ab. | |
| 86 | (controlled adj7 (study or design or trial)).ti,ab. | |
| 87 | (volunteer or volunteers).ti,ab. | |
| 88 | Human experiment/ | |
| 89 | Trial.ti. | |
| 90 | or/71-89 | |
| 91 | (Random$ adj sample$ adj7 (“cross section$” or questionnaire$1 or survey$1 or database$1)).ti,ab. not (comparative study/ or controlled study/ or randomi$ed controlled.ti,ab. or randomly assigned.ti,ab.) | |
| 92 | Cross-sectional study/ not (randomized controlled study/ or controlled clinical study/ or controlled study/ or randomi?ed controlled.ti,ab. or control groups$1.ti,ab.) | |
| 93 | (((case adj control$) and random$) not randomi?ed controlled).ti,ab. | |
| 94 | (Systematic review not (trial or study)).ti. | |
| 95 | (nonrandom$ not random$).ti,ab. | |
| 96 | “random field$.”ti,ab. | |
| 97 | (random cluster adj3 sampl$).ti,ab. | |
| 98 | (review.ab. and review.pt.) not trial.ti. | |
| 99 | (“we searched.”ab. and review.ti.) or review.pt. | |
| 100 | “update review.”ab. | |
| 101 | (databases adj4 searched).ab. | |
| 102 | (rat or rats or mouse or mice or swine or porcine or murine or sheep or lambs or pigs or piglets or rabbit or rabbits or cat or cats or dog or dogs or cattle or bovine or monkey or monkeys or trout or marmoset$1).ti. and animal experiment/ | |
| 103 | Animal experiment/ not (human experiment/ or human/) | |
| 104 | or/91-103 | |
| 105 | 90 not 104 | Cochrane Sensitive Therapy filter terms (Box 3.e) |
| 106 | 67 and 90 | Trials results |
| 107 | 70 and 105 | Cochrane filter results |
| 108 | 106 or 107 | Final results |
| 109 | remove duplicates from 108 | Duplicates removed |
Database: Ovid MEDLINE—Epub Ahead of Print, In-Process and Other Non-Indexed Citations, Ovid MEDLINE® Daily and Ovid MEDLINE®. Dates: 1946 to 2024 March 21
| # | Searches | Comment |
|---|---|---|
| 1 | ((operator* or phlebotomist* or nurse* or clinician* or doctor*) adj2 (technical or technique* or skill*)).ti,ab,kf. | |
| 2 | pain measurement/ or exp pain/ or (pain or pains or pained or painful* or distress*).ti,ab,kf. | |
| 3 | Visual analog scale/ or (instrument* or scale* or assess* or measure* or degree* or score* or scoring).ti,ab,kf. | |
| 4 | (visual adj2 analog adj2 (instrument* or scale* or assess* or measure* or degree* or score* or scoring)).ti,ab,kf. | |
| 5 | Pain Perception/ or Nociception/ or Sensory Thresholds/ or Pain Threshold/ or (nociception or nociperception).ti,ab,kf. | |
| 6 | milk, human/ or ((breast or hind or mother* or maternal*) adj2 milk).ti,ab,kf. or hindmilk.ti,ab,kf. | |
| 7 | breastfeeding/ or (breastfeeding or breastfed or “breast-feeding”).ti,ab,kf. | |
| 8 | Pacifiers/ or (“non-nutritive suck*” or “non lactating nipple*” or “non-lactating nipple*” or pacifier* or pacifying).ti,ab,kf. | |
| 9 | Infant Formula/ or ((baby or infan* or feeding or milk) adj2 formula*).ti,ab,kf. | |
| 10 | sucrose/ or (sucrose or glucose or saccharose or ((cane or beet) adj2 sugar*) or microtal or “saccharum album” or tabfine).ti,ab,kf. | |
| 11 | lactose/ or fructose/ or (lactose or fructose).ti,ab,kf. | |
| 12 | exp sweetening agents/ or (sweetener* or sweetening or sugar).ti,ab,kf. | |
| 13 | exp Kangaroo-Mother Care Method/ or (swaddl* or (facilitat* adj2 tuck*) or “skin to skin” or “skin-to-skin” or (kangaroo adj2 care) or “co-bedding” or “co bedding” or (bed adj2 shar*)).ti,ab,kf. | |
| 14 | patient positioning/ or posture/ or prone position/ or supine position/ | |
| 15 | (positioning or positions or positioned or containment or containing).ti,ab,kf. | |
| 16 | (rocking or holding or swinging or cuddling).ti,ab,kf. | |
| 17 | (rubbing or talking or shushing or comforting).ti,ab,kf. | |
| 18 | Sucking Behavior/ or (sucking or suck or sucks or sucked).ti,ab,kf. | |
| 19 | heating/ or humidity/ or lighting/ or temperature/ or ventilation/ or warming.ti,ab,kf. | |
| 20 | (heating or humidity or lighting or lights or lighted or temperature or ventilation or warming).ti,ab,kf. | |
| 21 | “cluster* of procedure*.”ti,ab,kf. | |
| 22 | ((parent* or mother* or father* or maternal* or paternal*) adj3 presen*).ti,ab,kf. | |
| 23 | exp Anesthetics, Local/ or ((local or topic or topical*) adj3 (anesthetic* or anaesthetic*)).mp. | |
| 24 | acetaminophen/ or (“a-mol” or abenol or acamol or acenol or acephen or acetalgin or “acetamino phenol” or acetaminophen* or acetamol or acetomenophen or acetylaminophenol or adorem or afebrin or algiafin or algocit or algotropyl or alphagesic or alvedon or amadil or “anacin 3” or anaflon or analgiser or apamide or apap or apirex or apotel or arthralgen or atamel or “ben-u-ron” or benuron or biogesic or bodrex or calapol or calodol or calonal or calpol or causalon or cemol or christamol or claradol or clocephen or “cp 500” or cp500 or dafalgan or daga or datril or depon or depyretin or dirox or dismifen or disprol or dolal or dolex or doliprane or dolitabs or dolofen or dolomol or dolorol or dolotemp or dolprone or doltem or drilan or duorol or dymadon or efferalgan or efferalganodis or efferelgan or enelfa or eneril or eraldor or exopon or expandol or febrilix or fendon or fervex or fibrinol or fortolin or gelocatil or “geluprane 500” or gunaceta or hedex or helporal or “infants’ feverall” or injectapap or janupap or kamolas or kyofen or lekadol or lemgrip or letamol or liquiprin or lotemp or lyteca or malidens or medamol or meforagesic or metagesic or metalid or mexalen or “milidon 500” or minopan or mypara or nalgesik or napamol or napap or naprex or nebs or “nektol 500” or neodalmin or neopap or nevral or nilapur or nobedon or nysacetol or ofirmev or pacemol or pacimol or pamal or pamol or panadol or panamax or panasorb or panodil or paracet or paracetaminophenol or paracetamol* or parageniol or paragin or paralen or paralief or paramax or paramidol or parapaed or paratabs or parvid or pasolind or paximol or pedipan or perfalgan or phenaphen or pinex or polarfen or predimol or puernol or pyrigesic or raperon or rapidol or relaphen or reliv or remedol or revanin or rhodapap or salzone or serimol or setamol or sinaspril or sinedol or sinpro or supofen or tabalgin or tachipirin* or taganopain or tapar or tempra or tempte or temzzard or termofren or tralgon or tramil or treuphadol or turpan or tylenol or tylex or valadol or winadol or winasorb or xebramol or zolben or zydinol).mp. or 103-90-2.rn. | |
| 25 | ibuprofen/ or (“act-3” or “adex 200” or advil or afebril or aktren or algifor or algofen or algoflex or allipen or “am-fam 400” or anadvil or analgyl or anbifen or anco or andran or anflagen or antarene or antiflam or ibuprofen or “atril 300” or attritin or balkaprofen or bestafen or betaprofen or bifen or bluton or brufanic or brufen or brufort or brugesic or brumed or buburone or bufect or bufohexal or bupogesic or burana or butacortelone or caldolor or “cap-profen” or cenbufen or motrin or combiflam or contraneural or cuprofen or “dc 7034” or dc7034 or “dg 7034” or dg7034 or dibufen or “dolan fp” or dolgit or dolocyl or dolodolgit or “dolofen-f” or dolomax or dolormin or dolval or “donjust b” or dorival or druisel or easifon or ecoprofen or emflam or epobron or exidol or expanfen or febratic or febryn or femapirin or fenalgic or fenbid or flamicon or “h-loniten” or halprin or haltran or “ib-100” or ibofen or ibosure or ibu or ibuberl or ibudak or ibufen or ibuflam or ibufug or ibugel or ibugesic or ibulgan or ibuloid or ibumetin or ibupen or ibupirac or ibuprin or ibuprocin or ibuprofen or “klinge 600” or ibuprofene or ibuprohm or iburon or ibusal or ibustar or ibusynth or ibutop or “idyl sr” or infibu or ipren or irfen or isdol or isodol or junifen or kontraneural or lamidon or librofem or lidifen or liptan or lopane or malafene or maxagesic or “mcn r 1451” or medicol or medipren or mediprin or mensoton or motrin or mynosedin or “nagifen-d” or napacetin or neobrufen or nerofen or neutropain or nobfelon or nobgen or “norflam-t” or noritis or norton or novogent or novoprofen or nugin or nuprin or nureflex or nurofen or ostarin or ostofen or paduden or panafen or pedea or perofen or proartinal or profen or profeno or proflex or proris or provon or quadrax or rafen or ranofen or rebugen or renidon or reuvol or rhelafen or roidenin or rufen or rupan or schufen or seclodin or “solufen lidose” or spedifen or spifen or syntofene or tabalon or taskine or tatanal or tofen or trendar or umafen or unipro or upfen or uprofen or urem or zofen).mp. or (15687-27-1 or 31121-93-4 or 527688-20-6 or 79261-49-7).rn. | |
| 26 | analgesics, short-acting/ or ((“short acting” or “short-acting”) adj2 analgesic*).mp. | |
| 27 | Conscious Sedation/ or ((conscious or moderate) adj2 sedat*).ti,ab,kf. | |
| 28 | narcotics/ or (narcotic or narcotics or stupefacient).mp. | |
| 29 | alfentanil/ or (alfenil or alfenta or “alfentanil hydrochloride” or alfentanyl or brevafen or fanaxal or fentalim or “r 39,209” or “r 39209” or rapifen).mp. or (69049-06-5 or 71195-58-9).rn. | |
| 30 | dihydromorphine/ or (dihydromorphine or hydromorphine or paramorphan).mp. or (1421-28-9 or 509-60-4).rn. | |
| 31 | ethylmorphine/ or (codethyline or diolan or dionine or “ethyl morphine” or ethylmorfine or ethylmorphin or “morphine ethyl ether”).mp. or (125-30-4 or 76-58-4).rn. | |
| 32 | fentanyl/ or (abstral or “ap 48” or ap48 or duragesic or fentamyl or fentanil or fentanyl or fetnanyl or instanyl or ionsys or lazanda or leptanal or onsolis or pecfent or phentanyl or “r 4263” or r4263 or rapinyl or recuvyra or subsys or tanyl or transfenta).mp. or 437-38-7.rn. | |
| 33 | morphine/ or (anpec or morphine or duromorph or epimorph or miro or morfin or morfine or morphia or morphin or morphine or morphinium or morphium or opso or skenan).mp. or (52-26-6 or 57-27-2).rn. | |
| 34 | sufentanil/ or (“arx 01” or arx01 or fentathianyl or fentathienyl or fentatienil or “r 30,730” or “r 30730” or “r30,730” or r30730 or sufentanyl or sulfentanil or sulfentanyl or zalviso).mp. or 56030-54-7.rn. | |
| 35 | exp Analgesics, Non-Narcotic/ or ((“non narcotic” or “non-narcotic”) adj2 (analgesi* or analgetic*)).mp. | |
| 36 | administration, topical/ or ((local or topic or topical*) adj3 (administration* or administer* or applicat* or delivery or dose* or dosage* or instillation* or infusion* or inject* or medication or treatment* or therap*)).ti,ab,kf. | |
| 37 | (vapo-coolant* or vapocoolant*).ti,ab,kf. | |
| 38 | therapeutic touch/ or (therapeutic adj2 touch).ti,ab,kf. or sensory art therapies/ or (sensory adj2 art adj2 therap*).ti,ab,kf. or music therapy/ or speleotherapy/ or speleotherap*.ti,ab,kf. | |
| 39 | Music/ or music.ti,ab,kf. | |
| 40 | Noise/ or (noise or noises).ti,ab,kf. or voice/ or voice.ti,ab,kf. or sound/ or sound*.ti,ab,kf. | |
| 41 | Emotion/ or (emotion* adj2 (factor* or response* or status or express*)).ti,ab. or fear/ or anxiety/ or (fear* or anxiet* or anxious*).ti,ab,kf. | |
| 42 | facial expression/ or gesture/ or ((facial adj5 express*) or grimace* or grimacing or gesture*).ti,ab,kf. | |
| 43 | crying/ or (crying or cries or cry or weeping).ti,ab,kf. | |
| 44 | pleasure/ or smell/ or (pleasure* or aroma* or odors or odor or odour* or scent* or smell* or olfaction or olfactory).ti,ab,kf. or taste/ or (gustation or gustatory or taste or tasting).ti,ab,kf. or touch/ or (haptic or tactile or touch or tactual).ti,ab,kf. or ((vibrating or vibration) adj2 (sense or perception or sensation or sensitivity)).ti,ab,kf. | |
| 45 | attitude/ or “attitude of health personnel”/ or attitude to health/ or health knowledge, attitudes, practice/ or Professional-Family Relations/ | |
| 46 | maternal behavior/ or parent-child relations/ or father-child relations/ or mother-child relations/ or maternal-fetal relations/ or paternal behavior/ | |
| 47 | exp parents/ or ((Parent* or mother* or maternal* or paternal or father*) adj2 (presen* or coaching or training or educat*)).ti,ab,kf. | |
| 48 | stress, psychological/ or ((mental or psychologic* or nervous or psychic) adj2 (stress* or tension)).ti,ab,kf. | |
| 49 | stress, physiological/ or ((biologic* or physiologic* or organismal) adj2 stress*).ti,ab,kf. or oxidative stress/ or ((oxidant or oxidative*) adj2 stress*).ti,ab,kf. | |
| 50 | Heart Rate/ or ((heart adj2 rate*) or “beat to beat variab*” or “beat-to-beat variab*”).ti,ab,kf. | |
| 51 | Blood Pressure/ or ((blood adj2 pressure) or hypertensi* or hypotensi*).ti,ab,kf. | |
| 52 | Respiratory Rate/ or ((respirat* or breath*) adj2 (rate* or change* or fluctuat*)).ti,ab,kf. | |
| 53 | Blood Gas Monitoring, Transcutaneous/ or ((Transcutaneous adj3 monitor*) or tcpo2 or tcpco2).ti,ab,kf. | |
| 54 | Spectroscopy, Near-Infrared/ or ((“near-infrared” or “near infrared”) adj2 spectroscop*).ti,ab,kf. or NIRS.ti,ab,kf. | |
| 55 | oximetry/ or hypoxia/ or (oximetr* or hypoxia or hypoxic).ti,ab,kf. | |
| 56 | or/1-55 | Pain measurement or intervention terms |
| 57 | limit 56 to “all infant (birth to 23 months)” | |
| 58 | infant/ or infant, newborn/ or infant, low birth weight/ or infant, small for gestational age/ or infant, very low birth weight/ or infant, extremely low birth weight/ or infant, postmature/ or infant, premature/ or infant, extremely premature/ | |
| 59 | Neonatology/ | |
| 60 | (newborn* or “new-born*” or baby* or babies or neonat* or perinat* or postnat* or “peri-nat*” or “post-nat*” or preemie* or prematur* or “pre-mature” or “pre-term” or prematuritas or preterm or “low birth weight” or “low birth-weight” or “low birthweight” or underweight or LBW or ELBW or “small for gestational age” or “small for date” or VLBW or NICU*).mp. | |
| 61 | Intensive Care Units, Neonatal/ | |
| 62 | or/58-61 | Neonatal terms |
| 63 | 57 or (56 and 62) | Age group and interventions results |
| 64 | catheterization, central venous/ | |
| 65 | ((central or venous) adj3 catheter*).ti,ab,kf. | |
| 66 | catheters/ or catheters, indwelling/ | |
| 67 | ((“in-dwelling” or indwelling or implantable) adj3 catheter*).ti,ab,kf. | |
| 68 | vascular access devices/ or central venous catheters/ | |
| 69 | ((arterial* or “intra-arterial*” or central* or vascular or venous) adj3 (access or line or lines or catheter* or device* or placed* or port or reservoir*)).ti,ab,kf. | |
| 70 | (venous adj3 (cannual* or canula* or catheter* or administration* or administer* or applicat* or delivery or dose* or dosage* or instillation* or infusion* or inject* or medication or treatment* or therap* or punctur* or poke or pokes or tap or taps or prick*)).ti,ab,kf. | |
| 71 | (Seldinger* adj2 Techni*).ti,ab,kf. | |
| 72 | CATHETERIZATION, PERIPHERAL/ | |
| 73 | ((picc or peripheral*) adj3 (catheter* or insert* or line or lines or placement*)).ti,ab,kf. | |
| 74 | ((needle* or catheter* or cannula* or PICC or syringe*) adj3 (size or sizes or sizing or gauge* or guage*)).ti,ab,kf. | |
| 75 | or/64-74 | PICC terms |
| 76 | 63 and 75 | PICC results |
| 77 | limit 76 to humans | |
| 78 | (human or humans or patient*).ti,ab,kf. | |
| 79 | 77 or (76 and 78) | Human limit |
| 80 | controlled clinical trial.pt. | |
| 81 | randomized controlled trial.pt. | |
| 82 | multicenter study.pt. | |
| 83 | randomized.ab. | |
| 84 | placebo.ab. | |
| 85 | drug therapy.fs. | |
| 86 | randomly.ab. | |
| 87 | trial.ab. | |
| 88 | groups.ab. | |
| 89 | or/80-88 | |
| 90 | exp animals/ not humans.sh. | |
| 91 | 89 not 90 | Cochrane Therapy Filter (Box 6.4.c) |
| 92 | 79 and 91 | Limit to RCTs |
| 93 | ((control* or random* or multicenter or multicentre) adj2 trial*).ti,ab,kf. | |
| 94 | 79 and 93 | Textword RCT terms |
| 95 | 94 or 92 | Final results |
Database: CINAHL Plus. Dates: 1983 to 2024 March 22
| # | Searches | Comment |
|---|---|---|
| S1 | (MH “Pain Measurement”) OR (MH “Nociceptive Pain”) OR (MH “Pain”) OR (MH “Pain Threshold”) OR (MH “Visual Analog Scaling”) OR TX ((operator* OR phlebotomist* OR nurse* OR clinician* OR doctor*) N2 (technical OR technique* OR skill*)) | |
| S2 | TX (pain or pains or pained or painful* or distress* or nociception or nociperception) | |
| S3 | (MH “Milk, Human”) OR TI (breastfeeding OR breastfed OR “breast-feeding”) OR AB (breastfeeding OR breastfed OR “breast-feeding”) | |
| S4 | (MH “Breast Feeding”) or TI ((breast or hind or mother* or maternal*) N2 milk) OR AB ((breast or hind or mother* or maternal*) N2 milk) | |
| S5 | (MH “Bottle Feeding”) OR (MH “Infant Formula”)or TI ((baby or infan* or feeding or milk) N2 formula*) OR AB ((baby or infan* or feeding or milk) N2 formula*) | |
| S6 | (MH “Pacifiers”) OR TI (“non-nutritive suck*” or “non lactating nipple*” or “non-lactating nipple*” or pacifier* or pacifying) OR AB (“non-nutritive suck*” or “non lactating nipple*” or “non-lactating nipple*” or pacifier* or pacifying) | |
| S7 | (MH “Sucralfate”) OR (MH “Sucrose”) OR (MH “Lactose”) OR (MH “Fructose”) OR TX (sucrose or glucose or saccharose or lactose or fructose or ((cane or beet) N2 sugar*) or microtal or “saccharum album” or tabfine) | |
| S8 | (MH “Sweetening Agents+”) OR TI (sweetener* or sweetening or sugar) OR AB (sweetener* or sweetening or sugar) | |
| S9 | (MH “Kangaroo Care”) OR TX (swaddl* or (facilitat* N2 tuck*) or “skin to skin” or “skin-to-skin” or (kangaroo N2 care) or “co-bedding” or “co bedding” or (bed N2 shar*)) OR (MH “Bed Sharing”) | |
| S10 | (MH “Sucking Behavior”) OR TI (sucking or suck or sucks or sucked) OR AB (sucking or suck or sucks or sucked) | |
| S11 | (MH “Anesthetics, Local+”) OR TI ((local or topical*) N3 (anesthetic* or anaesthetic*)) OR AB ((local or topical*) N3 (anesthetic* or anaesthetic*)) | |
| S12 | (MH “Acetaminophen”) OR TX (“a-mol” or abenol or acamol or acenol or acephen or acetalgin or “acetamino phenol” or acetaminophen* or acetamol or acetomenophen or acetylaminophenol or adorem or afebrin or algiafin or algocit or algotropyl or alphagesic or alvedon or amadil or “anacin 3” or anaflon or analgiser or apamide or apap or apirex or apotel or arthralgen or atamel or “ben-u-ron” or benuron or biogesic or bodrex or calapol or calodol or calonal or calpol or causalon or cemol or christamol or claradol or clocephen or “cp 500” or cp500 or dafalgan or daga or datril or depon or depyretin or dirox or dismifen or disprol or dolal or dolex or doliprane or dolitabs or dolofen or dolomol or dolorol or dolotemp or dolprone or doltem or drilan or duorol or dymadon or efferalgan or efferalganodis or efferelgan or enelfa or eneril or eraldor or exopon or expandol or febrilix or fendon or fervex or fibrinol or fortolin or gelocatil or “geluprane 500” or gunaceta or hedex or helporal or “infants’ feverall” or injectapap or janupap or kamolas or kyofen or lekadol or lemgrip or letamol or liquiprin or lotemp or lyteca or malidens or medamol or meforagesic or metagesic or metalid or mexalen or “milidon 500” or minopan or mypara or nalgesik or napamol or napap or naprex or nebs or “nektol 500” or neodalmin or neopap or nevral or nilapur or nobedon or nysacetol or ofirmev or pacemol or pacimol or pamal or pamol or panadol or panamax or panasorb or panodil or paracet or paracetaminophenol or paracetamol* or parageniol or paragin or paralen or paralief or paramax or paramidol or parapaed or paratabs or parvid or pasolind or paximol or pedipan or perfalgan or phenaphen or pinex or polarfen or predimol or puernol or pyrigesic or raperon or rapidol or relaphen or reliv or remedol or revanin or rhodapap or salzone or serimol or setamol or sinaspril or sinedol or sinpro or supofen or tabalgin or tachipirin* or taganopain or tapar or tempra or tempte or temzzard or termofren or tralgon or tramil or treuphadol or turpan or tylenol or tylex or valadol or winadol or winasorb or xebramol or zolben or zydinol) | |
| S13 | (MH “Ibuprofen”) OR (“act-3” or “adex 200” or advil or afebril or aktren or algifor or algofen or algoflex or allipen or “am-fam 400” or anadvil or analgyl or anbifen or anco or andran or anflagen or antarene or antiflam or ibuprofen or “atril 300” or attritin or balkaprofen or bestafen or betaprofen or bifen or bluton or brufanic or brufen or brufort or brugesic or brumed or buburone or bufect or bufohexal or bupogesic or burana or butacortelone or caldolor or “cap-profen” or cenbufen or motrin or combiflam or contraneural or cuprofen or “dc 7034” or dc7034 or “dg 7034” or dg7034 or dibufen or “dolan fp” or dolgit or dolocyl or dolodolgit or “dolofen-f” or dolomax or dolormin or dolval or “donjust b” or dorival or druisel or easifon or ecoprofen or emflam or epobron or exidol or expanfen or febratic or febryn or femapirin or fenalgic or fenbid or flamicon or “h-loniten” or halprin or haltran or “ib-100” or ibofen or ibosure or ibu or ibuberl or ibudak or ibufen or ibuflam or ibufug or ibugel or ibugesic or ibulgan or ibuloid or ibumetin or ibupen or ibupirac or ibuprin or ibuprocin or ibuprofen or “klinge 600” or ibuprofene or ibuprohm or iburon or ibusal or ibustar or ibusynth or ibutop or “idyl sr” or infibu or ipren or irfen or isdol or isodol or junifen or kontraneural or lamidon or librofem or lidifen or liptan or lopane or malafene or maxagesic or “mcn r 1451” or medicol or medipren or mediprin or mensoton or motrin or mynosedin or “nagifen-d” or napacetin or neobrufen or nerofen or neutropain or nobfelon or nobgen or “norflam-t” or noritis or norton or novogent or novoprofen or nugin or nuprin or nureflex or nurofen or ostarin or ostofen or paduden or panafen or pedea or perofen or proartinal or profen or profeno or proflex or proris or provon or quadrax or rafen or ranofen or rebugen or renidon or reuvol or rhelafen or roidenin or rufen or rupan or schufen or seclodin or “solufen lidose” or spedifen or spifen or syntofene or tabalon or taskine or tatanal or tofen or trendar or umafen or unipro or upfen or uprofen or urem or zofen) | |
| S14 | (MH “Patient Positioning”) OR (MH “Lateral Position”) OR (MH “Prone Position”) OR (MH “Supine Position”) OR TX (positioning or positions or positioned or containment or containing) | |
| S15 | TI (rocking or holding or swinging or cuddling or rubbing or talking or shushing or comforting) OR AB (rocking or holding or swinging or cuddling or rubbing or talking or shushing or comforting) | |
| S16 | TX ((“short acting” or “short-acting”) N2 analgesic*) | |
| S17 | (MH “Conscious Sedation”) OR TX ((conscious or moderate) adj2 sedat*) | |
| S18 | (MH “Alfentanil”) OR (alfenil or alfenta or “alfentanil hydrochloride” or alfentanyl or brevafen or fanaxal or fentalim or “r 39,209” or “r 39209” or rapifen) | |
| S19 | (MH “Dihydromorphinone”) OR TX (dihydromorphine or hydromorphine or paramorphan) | |
| S20 | TX (ethylmorphine/ or codethyline or diolan or dionine or “ethyl morphine” or ethylmorfine or ethylmorphin or “morphine ethyl ether”) | |
| S21 | (MH “Fentanyl”) OR TX (abstral or “ap 48” or ap48 or duragesic or fentamyl or fentanil or fentanyl or fetnanyl or instanyl or ionsys or lazanda or leptanal or onsolis or pecfent or phentanyl or “r 4263” or r4263 or rapinyl or recuvyra or subsys or tanyl or transfenta) | |
| S22 | (MH “Morphine”) OR TX (anpec or morphine or duromorph or epimorph or miro or morfin or morfine or morphia or morphin or morphine or morphinium or morphium or opso or skenan) | |
| S23 | (MH “Sufentanil”) OR TX (“arx 01” or arx01 or fentathianyl or fentathienyl or fentatienil or “r 30,730” or “r 30730” or “r30,730” or r30730 or sufentanyl or sulfentanil or sulfentanyl or zalviso) | |
| S24 | (MH “Temperature”) OR (MH “Lighting”) OR (MH “Ventilation”) OR (MH “Humidity”) OR (MH “Heating”) OR TI(warming) OR AB (warming) | |
| S25 | TI (“cluster* of procedure*”) OR AB (“cluster* of procedure*”0) | |
| S26 | TX ((“non narcotic” or “non-narcotic”) N2 (analgesic* or analgetic*)) | |
| S27 | (MH “Narcotics”) OR TI(narcotic or narcotics or stupefacient) OR AB(narcotic or narcotics or stupefacient) | |
| S28 | (MH “Administration, Topical”) OR TX ((local or topic or topical*) N3 (administration* or administer* or applicat* or delivery or dose* or dosage* or instillation* or infusion* or inject* or medication or treatment* or therap*)) | |
| S29 | TX (vapo-collant* or vapocoolant*) | |
| S30 | (MH “Therapeutic Touch”) OR TX (therapeutic N2 touch) OR TX (sensory N2 art N2 therap*) | |
| S31 | (MH “Music Therapy”) OR (MH “Music”) OR TX (music or speleotherap*) | |
| S32 | (MH “Noise”) OR (MH “Sound”) OR (MH “Voice”) OR (MH “Taste”) OR (MH “Touch”) OR TI(noise* or voice* or sound* or gustation or gustatory or taste or tasting or haptic or tactile or touch or tactual) OR AB(noise* or voice* or sound* or gustation or gustatory or taste or tasting or haptic or tactile or touch or tactual) | |
| S33 | (MH “Emotions”) OR (MH “Anxiety”) OR (MH “Fear”) OR (MH “Suffering”) OR TX (emotion* N2 (factor* or response* or status or express*)) OR TX (fear* or anxiet* or anxious*) | |
| S34 | (MH “Facial Expression”) OR TX ((facial N5 express*) or grimace* or grimacing or discomfort* or gesture*) | |
| S35 | (MH “Crying”) OR TX (crying or cries or cry or weeping) | |
| S36 | (MH “Pleasure”) OR (MH “Smell”) OR (MH “Odors”) OR TX (pleasure or aroma* or odors or odor or odour* or scent* or smell* or olfaction or olfactory) | |
| S37 | (MH “Attitude”) OR (MH “Attitude of Health Personnel”) OR (MH “Nurse Attitudes”) OR (MH “Physician Assistant Attitudes”) OR (MH “Physician Attitudes”) OR (MH “Pharmacist Attitudes”) OR (MH “Physical Therapist Attitudes”) OR (MH “Respiratory Therapist Attitudes”) OR (MH “Social Worker Attitudes”) OR (MH “Attitude to Health”) OR (MH “Health Beliefs”) OR (MH “Professional-Family Relations”) | |
| S38 | (MH “Maternal Behavior”) OR (MH “Parental Behavior”) OR (MH “Paternal Behavior”) OR (MH “Parent-Child Relations”) OR (MH “Father-Child Relations”) OR (MH “Mother-Child Relations”) OR (MH “Parent-Infant Relations”) OR (MH “Father-Infant Relations”) OR (MH “Mother-Infant Relations”) OR (MH “Parent-Infant Bonding”) OR (MH “Parenting”) | |
| S39 | (MH “Parents+”) OR TI (((parent* OR mother* OR father* OR maternal* OR paternal*) N3 presen*)) OR AB (((parent* OR mother* OR father* OR maternal* OR paternal*) N3 presen*)) | |
| S40 | (MH “Stress, Psychological”) OR TX ((mental or psychologic* or nervous or psychic) N2 (stress* or tension)) | |
| S41 | (MH “Stress, Physiological”) OR TX ((biologic* or physiologic* or organismal) N2 stress*) OR (MH “Oxidative Stress”) OR TX ((oxidant or oxidative*) N2 stress*) | |
| S42 | (MH “Heart Rate”) OR (MH “Heart Rate Variability”) OR TI((heart N2 rate*) or “beat to beat variab*” or “beat-to-beat variab*”) OR AB((heart N2 rate*) or “beat to beat variab*” or “beat-to-beat variab*”) | |
| S43 | (MH “Blood Pressure+”) OR TI((blood N2 pressure) or hypertensi* or hypotensi*) OR AB((blood N2 pressure) or hypertensi* or hypotensi*) | |
| S44 | (MH “Respiratory Rate”) OR TI((respirat* or breath*) N2 (rate* or change* or fluctuat*)) OR AB((respirat* or breath*) N2 (rate* or change* or fluctuat*)) | |
| S45 | (MH “Blood Gas Monitoring, Transcutaneous”) OR TI((Transcutaneous N3 monitor*) or tcpo2 or tcpco2) OR AB((Transcutaneous N3 monitor*) or tcpo2 or tcpco2) | |
| S46 | (MH “Spectroscopy, Near-Infrared”) OR TI((“near-infrared” or “near infrared”) N2 spectroscop*) OR TI(NIRS) OR AB((“near-infrared” or “near infrared”) N2 spectroscop*) OR AB(NIRS) | |
| S47 | (MH “Oximetry”) OR (MH “Pulse Oximetry”) or (MH “Anoxia”) OR TI(oximetr* or hypoxia or hypoxic) OR AB(oximetr* or hypoxia or hypoxic) | |
| S48 | S1 OR S2 OR S3 OR S4 OR S5 OR S6 OR S7 OR S8 OR S9 OR S10 OR S11 OR S12 OR S13 OR S14 OR S15 OR S16 OR S17 OR S18 OR S19 OR S20 OR S21 OR S22 OR S23 OR S24 OR S25 OR S26 OR S27 OR S28 OR S29 OR S30 OR S31 OR S32 OR S33 OR S34 OR S35 OR S36 OR S37 OR S38 OR S39 OR S40 OR S41 OR S42 OR S43 OR S44 OR S45 OR S46 OR S47 | Pain measurement or intervention terms |
| S49 | (MH “Infant”) OR (MH “Infant, Large for Gestational Age”) OR (MH “Infant, Low Birth Weight”) OR (MH “Infant, Small for Gestational Age”) OR (MH “Infant, Very Low Birth Weight”) OR (MH “Infant, Postmature”) OR (MH “Infant, Premature”) OR (MH “Infant, Newborn”) | |
| S50 | (MH “Neonatology”) OR (MH “Neonatal Intensive Care Nursing”) OR (MH “Intensive Care Units, Neonatal”) | |
| S51 | TX (infan* or newborn* or “new-born*” or baby* or babies or neonat* or perinat* or postnat* or “peri-nat*” or “post-nat*” or preemie* or prematur* or “pre-mature” or “pre-term” or prematuritas or preterm or “low birth weight” or “low birth-weight” or “low birthweight” or underweight *****or LBW or ELBW or “small for gestational age” or “small for date” or SGA or VLBW or NICU*) | |
| S52 | S49 OR S50 OR S51 | Neonatal terms |
| S53 | S48 AND S52 | Age group and interventions results |
| S54 | (MH “Randomized Controlled Trials”) OR (MH “Equivalence Trials”) OR (MH “Single-Blind Studies”) OR (MH “Double-Blind Studies”) OR (MH “Triple-Blind Studies”) | |
| S55 | (MH “Catheterization, Central Venous”) OR (MH “Catheterization, Peripheral Central Venous”) OR (MH “Catheterization, Peripheral”) OR (MH “Peripherally Inserted Central Catheters”) OR (MH “Catheters”) OR (MH “Vascular Access Devices”) OR (MH “Arterial Catheters”) OR (MH “Central Venous Catheters”) | |
| S56 | TX (((central or venous) N3 catheter*)) | |
| S57 | TX (((“in-dwelling” or indwelling or implantable) N3 catheter*)) | |
| S58 | TX (((arterial* or “intra-arterial*” or central* or vascular or venous) N3 (access or line or lines or catheter* or device* or placed* or port or reservoir*))) | |
| S59 | TX ((venous N3 (cannual* or canula* or catheter* or administration* or administer* or applicat* or delivery or dose* or dosage* or instillation* or infusion* or inject* or medication or treatment* or therap* or punctur* or poke or pokes or tap or taps or prick*))) | |
| S60 | TX (Seldinger* N2 Techni*) | |
| S61 | TX (((picc or peripheral*) N3 (catheter* or insert* or line or lines or placement*))) | |
| S62 | TX (((needle* or catheter* or cannula* or PICC or syringe*) N3 (size or sizes or sizing or gauge* or guage*))) | PICC terms |
| S63 | S55 OR S56 OR S57 OR S58 OR S59 OR S60 OR S61 OR S62 | PICC results |
| S64 | S53 AND S63 | Base clinical set |
| S65 | S54 AND S64 | Therapy trial terms |
| S66 | S52 AND S63 | Limiters—Clinical Queries: Therapy—High Specificity |
| S67 | S65 OR S66 | Final results |
Database: Cochrane Central Register of Controlled Trials (CENTRAL). Dates: Issue 2 of 12, 2024 February
| # | Searches | Comment |
|---|---|---|
| 1 | ((operator* or phlebotomist* or nurse* or clinician* or doctor*) NEAR/2 (technical or technique* or skill*)):ti,ab | |
| 2 | [mh ^“pain measurement”] or [mh pain] or (pain or pains or pained or painful* or distress*):ti,ab | |
| 3 | [mh ^“Visual analog scale”] or (instrument* or scale* or assess* or measure* or degree* or score* or scoring):ti,ab | |
| 4 | [mh ^“Pain Perception”] or [mh ^Nociception] or [mh ^”Sensory Thresholds”] or [mh ^”Pain Threshold”] or (nociception or nociperception):ti,ab | |
| 5 | [mh ^“milk, human”] or ((breast or hind or mother* or maternal*) NEAR/2 milk):ti,ab or hindmilk:ti,ab | |
| 6 | [mh ^breastfeeding] or (breastfeeding or breastfed or “breast-feeding”):ti,ab | |
| 7 | [mh ^Pacifiers] or (“non-nutritive suck” or “non-nutritive sucking” or “non lactating nipple” or “non lactating nipple” or “non-lactating nipple” or “non-lactating nipples” or pacifier* or pacifying):ti,ab | |
| 8 | [mh ^“Infant Formula”] or ((baby or infan* or feeding or milk) NEAR/2 formula*):ti,ab | |
| 9 | [mh ^sucrose] or (sucrose or glucose or saccharose or ((cane or beet) NEAR/2 sugar*) or microtal or “saccharum album” or tabfine):ti,ab | |
| 10 | [mh ^lactose] or [mh ^fructose] or (lactose or fructose):ti,ab | |
| 11 | [mh ^“sweetening agents”] or (sweetener* or sweetening or sugar):ti,ab | |
| 12 | [mh “Kangaroo-Mother Care Method”] or (swaddl* or (facilitat* NEAR/2 tuck*) or “skin to skin” or “skin-to-skin” or (kangaroo NEAR/2 care) or “co-bedding” or “co bedding” or (bed NEAR/2 shar*)):ti,ab | |
| 13 | [mh ^“patient positioning”] or [mh ^posture] or [mh ^”prone position”] or [mh ^”supine position”] | |
| 14 | (rocking or holding or swinging or cuddling):ti,ab | |
| 15 | (rubbing or talking or shushing or comforting):ti,ab | |
| 16 | [mh ^“Sucking Behavior”] or (sucking or suck or sucks or sucked):ti,ab | |
| 17 | [mh ^heating] or [mh ^humidity] or [mh ^lighting] or [mh ^temperature] or [mh ^ventilation] or warming:ti,ab | |
| 18 | (cluster* NEAR/2 procedure*):ti,ab | |
| 19 | [mh “Anesthetics, Local”] or ((local or topic or topical*) NEAR/3 (anesthetic* or anaesthetic*)):ti,ab | |
| 20 | [mh ^acetaminophen] or (“a-mol” or abenol or acamol or acenol or acephen or acetalgin or “acetamino phenol” or acetaminophen* or acetamol or acetomenophen or acetylaminophenol or adorem or afebrin or algiafin or algocit or algotropyl or alphagesic or alvedon or amadil or “anacin 3” or anaflon or analgiser or apamide or apap or apirex or apotel or arthralgen or atamel or “ben-u-ron” or benuron or biogesic or bodrex or calapol or calodol or calonal or calpol or causalon or cemol or christamol or claradol or clocephen or “cp 500” or cp500 or dafalgan or daga or datril or depon or depyretin or dirox or dismifen or disprol or dolal or dolex or doliprane or dolitabs or dolofen or dolomol or dolorol or dolotemp or dolprone or doltem or drilan or duorol or dymadon or efferalgan or efferalganodis or efferelgan or enelfa or eneril or eraldor or exopon or expandol or febrilix or fendon or fervex or fibrinol or fortolin or gelocatil or “geluprane 500” or gunaceta or hedex or helporal or “infants’ feverall” or injectapap or janupap or kamolas or kyofen or lekadol or lemgrip or letamol or liquiprin or lotemp or lyteca or malidens or medamol or meforagesic or metagesic or metalid or mexalen or “milidon 500” or minopan or mypara or nalgesik or napamol or napap or naprex or nebs or “nektol 500” or neodalmin or neopap or nevral or nilapur or nobedon or nysacetol or ofirmev or pacemol or pacimol or pamal or pamol or panadol or panamax or panasorb or panodil or paracet or paracetaminophenol or paracetamol* or parageniol or paragin or paralen or paralief or paramax or paramidol or parapaed or paratabs or parvid or pasolind or paximol or pedipan or perfalgan or phenaphen or pinex or polarfen or predimol or puernol or pyrigesic or raperon or rapidol or relaphen or reliv or remedol or revanin or rhodapap or salzone or serimol or setamol or sinaspril or sinedol or sinpro or supofen or tabalgin or tachipirin* or taganopain or tapar or tempra or tempte or temzzard or termofren or tralgon or tramil or treuphadol or turpan or tylenol or tylex or valadol or winadol or winasorb or xebramol or zolben or zydinol):ti,ab | |
| 21 | [mh ^ibuprofen] or (“act-3” or “adex 200” or advil or afebril or aktren or algifor or algofen or algoflex or allipen or “am-fam 400” or anadvil or analgyl or anbifen or anco or andran or anflagen or antarene or antiflam or ibuprofen or “atril 300” or attritin or balkaprofen or bestafen or betaprofen or bifen or bluton or brufanic or brufen or brufort or brugesic or brumed or buburone or bufect or bufohexal or bupogesic or burana or butacortelone or caldolor or “cap-profen” or cenbufen or motrin or combiflam or contraneural or cuprofen or “dc 7034” or dc7034 or “dg 7034” or dg7034 or dibufen or “dolan fp” or dolgit or dolocyl or dolodolgit or “dolofen-f” or dolomax or dolormin or dolval or “donjust b” or dorival or druisel or easifon or ecoprofen or emflam or epobron or exidol or expanfen or febratic or febryn or femapirin or fenalgic or fenbid or flamicon or “h-loniten” or halprin or haltran or “ib-100” or ibofen or ibosure or ibu or ibuberl or ibudak or ibufen or ibuflam or ibufug or ibugel or ibugesic or ibulgan or ibuloid or ibumetin or ibupen or ibupirac or ibuprin or ibuprocin or ibuprofen or “klinge 600” or ibuprofene or ibuprohm or iburon or ibusal or ibustar or ibusynth or ibutop or “idyl sr” or infibu or ipren or irfen or isdol or isodol or junifen or kontraneural or lamidon or librofem or lidifen or liptan or lopane or malafene or maxagesic or “mcn r 1451” or medicol or medipren or mediprin or mensoton or motrin or mynosedin or “nagifen-d” or napacetin or neobrufen or nerofen or neutropain or nobfelon or nobgen or “norflam-t” or noritis or norton or novogent or novoprofen or nugin or nuprin or nureflex or nurofen or ostarin or ostofen or paduden or panafen or pedea or perofen or proartinal or profen or profeno or proflex or proris or provon or quadrax or rafen or ranofen or rebugen or renidon or reuvol or rhelafen or roidenin or rufen or rupan or schufen or seclodin or “solufen lidose” or spedifen or spifen or syntofene or tabalon or taskine or tatanal or tofen or trendar or umafen or unipro or upfen or uprofen or urem or zofen):ti,ab | |
| 22 | [mh ^“analgesics, short-acting”] or ((“short acting” or “short-acting”) NEAR/2 analgesic*):ti,ab | |
| 23 | [mh ^“Conscious Sedation”] or ((conscious or moderate) NEAR/2 sedat*):ti,ab | |
| 24 | [mh ^narcotics] or (narcotic or narcotics or stupefacient):ti,ab | |
| 25 | [mh ^alfentanil] or (alfenil or alfenta or “alfentanil hydrochloride” or alfentanyl or brevafen or fanaxal or fentalim or “r 39,209” or “r 39209” or rapifen):ti,ab | |
| 26 | [mh ^dihydromorphine] or (dihydromorphine or hydromorphine or paramorphan):ti,ab | |
| 27 | [mh ^ethylmorphine] or (codethyline or diolan or dionine or “ethyl morphine” or ethylmorfine or ethylmorphin or “morphine ethyl ether”):ti,ab | |
| 28 | [mh ^fentanyl] or (abstral or “ap 48” or ap48 or duragesic or fentamyl or fentanil or fentanyl or fetnanyl or instanyl or ionsys or lazanda or leptanal or onsolis or pecfent or phentanyl or “r 4263” or r4263 or rapinyl or recuvyra or subsys or tanyl or transfenta):ti,ab | |
| 29 | [mh ^morphine] or (anpec or morphine or duromorph or epimorph or miro or morfin or morfine or morphia or morphin or morphine or morphinium or morphium or opso or skenan):ti,ab | |
| 30 | [mh ^sufentanil] or (“arx 01” or arx01 or fentathianyl or fentathienyl or fentatienil or “r 30,730” or “r 30730” or “r30,730” or r30730 or sufentanyl or sulfentanil or sulfentanyl or zalviso):ti,ab | |
| 31 | [mh “Analgesics, Non-Narcotic”] or ((“non narcotic” or “non-narcotic”) NEAR/2 (analgesi* or analgetic*)):ti,ab | |
| 32 | [mh ^“administration, topical”] or ((local or topic or topical*) NEAR/3 (administration* or administer* or applicat* or delivery or dose* or dosage* or instillation* or infusion* or inject* or medication or treatment* or therap*)):ti,ab | |
| 33 | (vapo-collant* or vapocoolant*):ti,ab | |
| 34 | [mh ^“therapeutic touch”] or [mh ^”sensory art therapies”] or [mh ^”music therapy”] or [mh ^speleotherapy] or (speleotherap* or (therapeutic NEAR/2 touch) or (sensory NEAR/2 art NEAR/2 therap*)):ti,ab | |
| 35 | [mh ^music] or music:ti,ab | |
| 36 | [mh ^Noise] or (noise or noises):ti,ab or [mh ^voice] or voice:ti,ab or [mh ^sound] or sound*:ti,ab | |
| 37 | [mh ^Emotion] or (emotion* NEAR/2 (factor* or response* or status or express*)):ti,ab or [mh ^fear] or [mh ^anxiety] or (fear* or anxiet* or anxious*):ti,ab | |
| 38 | [mh ^“facial expression”] or [mh ^gesture] or ((facial NEAR/5 express*) or grimace* or grimacing or gesture*):ti,ab | |
| 39 | [mh ^crying] or (crying or cries or cry or weeping):ti,ab | |
| 40 | [mh ^pleasure] or [mh ^smell] or (pleasure* or aroma* or odors or odor or odour* or scent* or smell* or olfaction or olfactory):ti,ab or [mh ^taste] or (gustation or gustatory or taste or tasting):ti,ab or [mh ^touch] or (haptic or tactile or touch or tactual):ti,ab or ((vibrating or vibration) NEAR/2 (sense or perception or sensation or sensitivity)):ti,ab | |
| 41 | [mh ^attitude] or [mh ^“attitude of health personnel”] or [mh ^”attitude to health”] or [mh ^”health knowledge, attitudes, practice”] or [mh “Professional-Family Relations”] | |
| 42 | [mh ^“maternal behavior”] or [mh ^”parent-child relations”] or[mh ^”father-child relations”] or [mh ^”mother-child relations”] or [mh ^”maternal-fetal relations”] or [mh ^”paternal behavior”] | |
| 43 | [mh ^parents] or ((Parent* or mother* or maternal* or paternal or father*) NEAR/2 (presen* or coaching or training or educat*)):ti,ab | |
| 44 | [mh ^“stress, psychological”] or ((mental or psychologic* or nervous or psychic) NEAR/2 (stress* or tension)):ti,ab | |
| 45 | [mh ^“stress, physiological”] or ((biologic* or physiologic* or organismal) NEAR/2 stress*) or [mh ^”oxidative stress”] or ((oxidant or oxidative*) NEAR/2 stress*):ti,ab | |
| 46 | [mh ^“Heart Rate”] or ((heart NEAR/2 rate*) or “beat to beat variable” or “beat-to-beat variables”):ti,ab | |
| 47 | [mh ^“Blood Pressure”] or ((blood NEAR/2 pressure) or hypertensi* or hypotensi*):ti,ab | |
| 48 | [mh ^“Respiratory Rate”] or ((respirat* or breath*) NEAR/2 (rate* or change* or fluctuat*)):ti,ab | |
| 49 | [mh ^“Blood Gas Monitoring, Transcutaneous”] or ((Transcutaneous NEAR/3 monitor*) or tcpo2 or tcpco2):ti,ab | |
| 50 | [mh ^“Spectroscopy, Near-Infrared”] or ((“near-infrared” or “near infrared”) NEAR/2 spectroscop*):ti,ab or NIRS:ti,ab | |
| 51 | [mh ^oximetry] or [mh ^hypoxia] or (oximetr* or hypoxia or hypoxic):ti,ab | |
| 52 | (positioning or positions or positioned or containment or containing):ti,ab | |
| 53 | {or #1-#52} | Pain measurement or intervention terms |
| 54 | [mh ^infant] or [mh ^“infant, newborn”] or [mh ^”infant, low birth weight”] or [mh ^”infant, small for gestational age”] or [mh ^”infant, very low birth weight”] or [mh ^”infant, extremely low birth weight”] or [mh ^”infant, postmature”] or [mh ^”infant, premature”] or [mh ^”infant, extremely premature”] | |
| 55 | [mh ^neonatology] | |
| 56 | (newborn* or “new-born” or “new-borns” or baby or babies or neonat* or perinat* or postnat* or “peri-natal” or “post-natal” or preemie* or prematur* or “pre-mature” or “pre-term” or prematuritas or preterm or “low birth weight” or “low birth-weight” or “low birthweight” or underweight or LBW or ELBW or “small for gestational age” or “small for date” or VLBW or NICU*):ti,ab | |
| 57 | [mh ^“Intensive Care Units, Neonatal”] | |
| 58 | {or #54-#57} | Neonatal terms |
| 59 | catheterization, central venous:kw or ((central or venous) NEXT2 catheter*):ti,ab | |
| 60 | catheters:kw or catheters, indwelling:kw or ((“in-dwelling” or indwelling or implantable) NEXT3 catheter*):ti,ab | |
| 61 | vascular access devices:kw or central venous catheters:kw | |
| 62 | (arterial or central* or vascular or venous or picc) NEXT2 (access or line or lines or catheter* or device* or placed* or port or reservoir*):ti,ab | |
| 63 | (venous next (cannula* or canula* or catheter* or administration* or administer* or applicat* or delivery or dose* or dosage* or instillation* or infusion* or inject* or medication or treatment* or therap* or punctur* or poke or pokes or tap or taps or tapping or tapped or prick*)):ti,ab | |
| 64 | (Seldinger Technique):ti,ab | |
| 65 | catherization, peripheral:kw | |
| 66 | ((picc or peripheral*) NEXT2 (catheter* or insert* or line or lines or placement*)):ti,ab | |
| 67 | ((needle* or catheter* or cannula* or PICC or syringe*) next (size or sizes or sizing or gauge* or guage*)):ti,ab | |
| 68 | {or #59-#67} | PICC terms |
| 69 | #53 and #58 and #68 | Base clinical set |
| 70 | human or humans or patient*:ti,ab | |
| 71 | #69 and #70 | Final results—human limit |
Database: APA PsycInfo. Dates: 1806 to 2024 March (Week 4)
| # | Searches | Comment |
|---|---|---|
| 1 | ((operator* or phlebotomist* or nurse* or clinician* or doctor*) adj2 (technical or technique* or skill*)).ti,ab,id. | |
| 2 | pain/ or pain measurement/ or pain perception/ or pain thresholds/ or suffering/ or distress/ | |
| 3 | (pain or pains or pained or painful* or distress* or nociception or nociperception).ti,ab,id. | |
| 4 | (instrument* or scale* or assess* or measure* or degree* or score* or scoring).ti,ab,id. | |
| 5 | lactation/ or ((breast or hind or mother* or maternal*) adj2 milk).ti,ab. or hindmilk.ti,ab,id. | |
| 6 | breast feeding/ or (breastfeeding or breastfed or “breast-feeding”).ti,ab,id. | |
| 7 | (“non-nutritive suck*” or “non lactating nipple*” or “non-lactating nipple*” or pacifier* or pacifying or dummy or dummies).ti,ab,id. | |
| 8 | bottle feeding/ or ((baby or infan* or feeding or milk) adj2 (fed or feeding or formula*)).ti,ab,id. | |
| 9 | sugars/ or (sucrose or glucose or saccharose or ((cane or beet) adj2 sugar*) or microtal or “saccharum album” or tabfine).ti,ab,id. | |
| 10 | (lactose or fructose).ti,ab,id. | |
| 11 | (sweetener* or sweetening or sugar).ti,ab,id. | |
| 12 | (swaddl* or (facilitat* adj2 tuck*) or “skin to skin” or “skin-to-skin” or (kangaroo adj2 care) or “co-bedding” or “co bedding” or (bed adj2 shar*)).ti,ab,id. | |
| 13 | (positioning or positions or positioned or containment or containing).ti,ab,id. | |
| 14 | (rocking or holding or swinging or cuddling).ti,ab,id. | |
| 15 | (rubbing or talking or shushing or comforting).ti,ab,id. | |
| 16 | Sucking/ or (sucking or suck or sucks or sucked).ti,ab,id. | |
| 17 | illumination/ or brightness perception/ or brightness constancy/ or (heating or humidity or lighting or light or lights or temperature or ventilation or warming).ti,ab,id. | |
| 18 | “cluster* of procedure*.”ti,ab,id. | |
| 19 | exp Local Anesthetics/ or ((local or topic or topical*) adj3 (administration* or administer* or applicat* or delivery or dose* or dosage* or instillation* or infusion* or inject* or medication or treatment* or therap*)).ti,ab,id. | |
| 20 | (“a-mol” or abenol or acamol or acenol or acephen or acetalgin or “acetamino phenol” or acetaminophen* or acetamol or acetomenophen or acetylaminophenol or adorem or afebrin or algiafin or algocit or algotropyl or alphagesic or alvedon or amadil or “anacin 3” or anaflon or analgiser or apamide or apap or apirex or apotel or arthralgen or atamel or “ben-u-ron” or benuron or biogesic or bodrex or calapol or calodol or calonal or calpol or causalon or cemol or christamol or claradol or clocephen or “cp 500” or cp500 or dafalgan or daga or datril or depon or depyretin or dirox or dismifen or disprol or dolal or dolex or doliprane or dolitabs or dolofen or dolomol or dolorol or dolotemp or dolprone or doltem or drilan or duorol or dymadon or efferalgan or efferalganodis or efferelgan or enelfa or eneril or eraldor or exopon or expandol or febrilix or fendon or fervex or fibrinol or fortolin or gelocatil or “geluprane 500” or gunaceta or hedex or helporal or “infants’ feverall” or injectapap or janupap or kamolas or kyofen or lekadol or lemgrip or letamol or liquiprin or lotemp or lyteca or malidens or medamol or meforagesic or metagesic or metalid or mexalen or “milidon 500” or minopan or mypara or nalgesik or napamol or napap or naprex or nebs or “nektol 500” or neodalmin or neopap or nevral or nilapur or nobedon or nysacetol or ofirmev or pacemol or pacimol or pamal or pamol or panadol or panamax or panasorb or panodil or paracet or paracetaminophenol or paracetamol* or parageniol or paragin or paralen or paralief or paramax or paramidol or parapaed or paratabs or parvid or pasolind or paximol or pedipan or perfalgan or phenaphen or pinex or polarfen or predimol or puernol or pyrigesic or raperon or rapidol or relaphen or reliv or remedol or revanin or rhodapap or salzone or serimol or setamol or sinaspril or sinedol or sinpro or supofen or tabalgin or tachipirin* or taganopain or tapar or tempra or tempte or temzzard or termofren or tralgon or tramil or treuphadol or turpan or tylenol or tylex or valadol or winadol or winasorb or xebramol or zolben or zydinol).mp. | |
| 21 | (“act-3” or “adex 200” or advil or afebril or aktren or algifor or algofen or algoflex or allipen or “am-fam 400” or anadvil or analgyl or anbifen or anco or andran or anflagen or antarene or antiflam or ibuprofen or “atril 300” or attritin or balkaprofen or bestafen or betaprofen or bifen or bluton or brufanic or brufen or brufort or brugesic or brumed or buburone or bufect or bufohexal or bupogesic or burana or butacortelone or caldolor or “cap-profen” or cenbufen or motrin or combiflam or contraneural or cuprofen or “dc 7034” or dc7034 or “dg 7034” or dg7034 or dibufen or “dolan fp” or dolgit or dolocyl or dolodolgit or “dolofen-f” or dolomax or dolormin or dolval or “donjust b” or dorival or druisel or easifon or ecoprofen or emflam or epobron or exidol or expanfen or febratic or febryn or femapirin or fenalgic or fenbid or flamicon or “h-loniten” or halprin or haltran or “ib-100” or ibofen or ibosure or ibu or ibuberl or ibudak or ibufen or ibuflam or ibufug or ibugel or ibugesic or ibulgan or ibuloid or ibumetin or ibupen or ibupirac or ibuprin or ibuprocin or ibuprofen or “klinge 600” or ibuprofene or ibuprohm or iburon or ibusal or ibustar or ibusynth or ibutop or “idyl sr” or infibu or ipren or irfen or isdol or isodol or junifen or kontraneural or lamidon or librofem or lidifen or liptan or lopane or malafene or maxagesic or “mcn r 1451” or medicol or medipren or mediprin or mensoton or motrin or mynosedin or “nagifen-d” or napacetin or neobrufen or nerofen or neutropain or nobfelon or nobgen or “norflam-t” or noritis or norton or novogent or novoprofen or nugin or nuprin or nureflex or nurofen or ostarin or ostofen or paduden or panafen or pedea or perofen or proartinal or profen or profeno or proflex or proris or provon or quadrax or rafen or ranofen or rebugen or renidon or reuvol or rhelafen or roidenin or rufen or rupan or schufen or seclodin or “solufen lidose” or spedifen or spifen or syntofene or tabalon or taskine or tatanal or tofen or trendar or umafen or unipro or upfen or uprofen or urem or zofen).mp. | |
| 22 | ((“short acting” or “short-acting”) adj2 analgesic*).mp. | |
| 23 | ((conscious or moderate) adj2 sedat*).ti,ab,id. | |
| 24 | exp narcotic drugs/ or (narcotic or narcotics or stupefacient).mp. | |
| 25 | (alfenil or alfenta or “alfentanil hydrochloride” or alfentanyl or brevafen or fanaxal or fentalim or “r 39,209” or “r 39209” or rapifen).mp. | |
| 26 | (dihydromorphine or hydromorphine or paramorphan).mp. | |
| 27 | (codethyline or diolan or dionine or “ethyl morphine” or ethylmorfine or ethylmorphin or “morphine ethyl ether”).mp. | |
| 28 | fentanyl/ or (abstral or “ap 48” or ap48 or duragesic or fentamyl or fentanil or fentanyl or fetnanyl or instanyl or ionsys or lazanda or leptanal or onsolis or pecfent or phentanyl or “r 4263” or r4263 or rapinyl or recuvyra or subsys or tanyl or transfenta).mp. | |
| 29 | morphine/ or (anpec or morphine or duromorph or epimorph or miro or morfin or morfine or morphia or morphin or morphine or morphinium or morphium or opso or skenan).mp. | |
| 30 | (“arx 01” or arx01 or fentathianyl or fentathienyl or fentatienil or “r 30,730” or “r 30730” or “r30,730” or r30730 or sufentanyl or sulfentanil or sulfentanyl or zalviso).mp. | |
| 31 | ((“non narcotic” or “non-narcotic”) adj2 (analgesic* or analgetic*)).mp. | |
| 32 | (vapo-coolant* or vapocoolant*).ti,ab,id. | |
| 33 | ((therapeutic adj2 touch) or (sensory adj2 art adj2 therap*)).ti,ab,id. or music therapy/ or speleotherap*.ti,ab,id. | |
| 34 | Music/ or music.ti,ab,id. | |
| 35 | loudness/ or “noise levels (work areas)”/ or white noise/ or (noise or noises).ti,ab,id. or voice/ or voice.ti,ab,id. or Auditory Stimulation/ or sound*.ti,ab,id. | |
| 36 | emotions/ or negative emotions/ or positive emotions/ or emotional states/ or (emotion* adj2 (factor* or response* or status or express*)).ti,ab,id. or fear/ or conditioned fear/ or anxiety/ or distress/ or suffering/ or (fear* or anxiet* or anxious* or distress or suffering).ti,ab,id. | |
| 37 | facial expressions/ or grimaces/ or smiles/ or gestures/ or ((facial adj5 express*) or grimace* or grimacing or discomfort* or gesture*).ti,ab,id. | |
| 38 | crying/ or infant vocalization/ or (crying or cries or cry or weeping).ti,ab,id. | |
| 39 | pleasure/ or olfactory perception/ or odor discrimination/ or olfactory thresholds/ or olfactory stimulation/ or (pleasure or aroma* or odors or odor or odour* or scent* or smell* or olfaction or olfactory).ti,ab,id. or taste perception/ or taste stimulation/ or (gustation or gustatory or taste or tasting).ti,ab,id. or tactual perception/ or cutaneous sense/ or texture perception/ or vibrotactile thresholds/ or (haptic or tactile or touch or tactual).ti,ab,id. or ((vibrating or vibration) adj2 (sense or perception or sensation or sensitivity)).ti,ab,id. or voice/ or voice.ti,ab,id. or auditory stimulation/ or sound*.ti,ab,id. | |
| 40 | attitudes/ or health attitudes/ or health personnel attitudes/ or therapist attitudes/ or psychologist attitudes/ or therapist role/ or ((professional* or practitioner* or physician* or nurse* or “care-giver*” or caregiver*) adj2 (client* or famil*)).ti,ab,id. | |
| 41 | parental attitudes/ or father child relations/ or mother child relations/ or parental involvement/ or parental role/ or parenting style/ | |
| 42 | exp parents/ or ((Parent* or mother* or maternal* or paternal or father*) adj2 (presen* or coaching or training or educat*)).ti,ab,id. | |
| 43 | stress/ or psychological stress/ or ((mental or psychologic* or nervous or psychic) adj2 (stress* or tension)).ti,ab,id. | |
| 44 | physiological stress/ or ((biologic* or physiologic* or organismal or oxidant or oxidative*) adj2 stress*).ti,ab,id. | |
| 45 | Heart Rate/ or ((heart adj2 rate*) or “beat to beat variab*” or “beat-to-beat variab*”).ti,ab,id. | |
| 46 | exp Blood Pressure/ or ((blood adj2 pressure) or hypertensi* or hypotensi*).ti,ab,id. | |
| 47 | ((respirat* or breath*) adj2 (rate* or change* or fluctuat*)).ti,ab,id. | |
| 48 | ((Transcutaneous adj3 monitor*) or tcpo2 or tcpco2).ti,ab,id. | |
| 49 | [Spectroscopy/ or ((“near-infrared” or “near infrared”) adj2 spectroscop*).ti,ab,kf. or NIRS.ti,ab,id.] | |
| 50 | (oximetr* or hypoxia or hypoxic).ti,ab,id. | |
| 51 | or/1-50 | Pain measurement or intervention terms |
| 52 | limit 51 to (120 neonatal < birth to age 1 mo > or 140 infancy < 2 to 23 mo>) | |
| 53 | birth weight/ or premature birth/ or neonatal intensive care/ | |
| 54 | (infan* or newborn* or “new-born*” or baby* or babies or neonat* or perinat* or postnat* or “peri-nat*” or “post-nat*” or preemie* or prematur* or “pre-mature” or “pre-term” or prematuritas or preterm or “low birth weight” or “low birth-weight” or “low birthweight” or underweight or LBW or ELBW or “small for gestational age” or “small for date” or VLBW or NICU*).mp. | |
| 55 | or/53-54 | Neonatal terms |
| 56 | 52 or (51 and 55) | Age group and interventions results |
| 57 | catheterization/ or ((central or venous) adj3 catheter*).ti,ab,id. | |
| 58 | ((“in-dwelling” or indwelling or implantable) adj3 catheter*).ti,ab,id. | |
| 59 | ((arterial* or “intra-arterial*” or central* or vascular or venous) adj3 (access or line or lines or catheter* or device* or placed* or port or reservoir*)).ti,ab,id. | |
| 60 | (venous adj3 (cannula* or canula* or catheter* or administration* or administer* or applicat* or delivery or dose* or dosage* or instillation* or infusion* or inject* or medication or treatment* or therap* or punctur* or poke or pokes or tap or taps or tapping or tapped or prick*)).ti,ab,id. | |
| 61 | Seldinger*.ti,ab,id. | |
| 62 | ((picc or peripheral*) adj3 (catheter* or insert* or line or lines or placement*)).ti,ab,id. | |
| 63 | ((needle* or catheter* or cannula* or PICC or syringe*) adj3 (size or sizes or sizing or gauge* or guage*)).ti,ab,id. | |
| 64 | or/57-63 | PICC terms |
| 65 | 56 and 64 | PICC results |
| 66 | limit 65 to human | Limit to humans |
| 67 | (human or humans or patient*).ti,ab,id. | Human textword terms |
| 68 | 66 or (65 and 67) | Human results |
| 69 | limit 68 to “0300 clinical trial” | Limit to Clinical Trial |
| 70 | randomized controlled trials/ or randomized clinical trials/ or exp experimental design/ or placebo/ or random sampling/ or exp treatment effectiveness evaluation/ | |
| 71 | ((control* or random* or multicenter or multicentre) adj2 trial*).ti,ab,id. | |
| 72 | randomized.ab. | |
| 73 | placebo.ab. | |
| 74 | randomly.ab. | |
| 75 | trial.ab. | |
| 76 | groups.ab. | |
| 77 | or/70-76 [****Trial terms*****] | Trial terms |
| 78 | 69 or (68 and 77) [****Final results****] | Final results |
| 79 | remove duplicates from 78 | Duplicates removed |
Contributor Information
Najla Tabbara, Department of Pharmacy, Mount Sinai Hospital, Toronto, Ontario; Institute of Health Policy, Management and Evaluation, Dalla Lana School of Public Health, University of Toronto, Toronto, Ontario.
Anna Taddio, Leslie Dan Faculty of Pharmacy, University of Toronto, Toronto, Ontario.
Elizabeth Uleryk, E.M. Uleryk Consulting, Mississauga, Ontario.
Vibhuti Shah, Institute of Health Policy, Management and Evaluation, Dalla Lana School of Public Health, University of Toronto, Toronto, Ontario; Department of Paediatrics, Mount Sinai Hospital, Toronto, Ontario.
SUPPLEMENT SPONSORSHIP
This article appears as part of the supplement “Procedural Pain Management in Neonates,” funded by Knowledge Synthesis Grant 147986, Canadian Institute of Health Research.
REGISTRATION AND PROTOCOL
This review is registered in PROSPERO (CRD42017060346). The protocol was prepared in adherence with PRISMA-P guidelines (26).
POTENTIAL CONFLICTS OF INTEREST
A. Taddio reports a University of Toronto Section 9 Trademark No. 924835 for CARD™ A. Taddio reports research funding from the Public Health Agency of Canada (2324-HQ-000142) and the Canadian Institutes of Health Research (FRN 159905). A. Taddio is the inaugural Glaxo-Smith-Kline (GSK) Research Chair in Vaccine Education and Practice-Oriented Tools. AT is the primary investigator and VS is the senior investigator for one of the included trials (51).
DATA AVAILABILITY
We thank Dr. Ballantyne for providing requested clarifications. All data inputted in the analyses were extracted from published studies and are publicly available. Data collection forms and analytic code are available upon request.
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Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.
Data Availability Statement
We thank Dr. Ballantyne for providing requested clarifications. All data inputted in the analyses were extracted from published studies and are publicly available. Data collection forms and analytic code are available upon request.