Pain management for placement of peripherally inserted central catheters in neonates: A systematic review and meta-analysis
Bibliographic record
Abstract
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.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.012 | 0.033 |
| Meta-epidemiology (narrow) | 0.003 | 0.001 |
| Meta-epidemiology (broad) | 0.020 | 0.036 |
| Bibliometrics | 0.006 | 0.006 |
| Science and technology studies | 0.001 | 0.001 |
| Scholarly communication | 0.003 | 0.002 |
| Open science | 0.002 | 0.002 |
| Research integrity | 0.002 | 0.002 |
| Insufficient payload (model declined to judge) | 0.004 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".