Summary of findings 1. Opioids compared to no treatment/placebo for procedural pain in neonates.
| Opioids compared to no treatment/placebo for procedural pain in neonates | ||||||
| Patient or population: neonates exposed to procedural pain Setting: neonatal units Intervention: opioids Comparison: no treatment/placebo | ||||||
| Outcomes | Anticipated absolute effects* (95% CI) | Relative effect (95% CI) | № of participants (studies) | Certainty of the evidence (GRADE) | Comments | |
| Risk with no treatment/placebo | Risk with opioids | |||||
| Pain, assessed using the PIPP/PIPP‐R pain scale, ranging from 0 to 21 and 0 to 18 in preterm infants < 28 weeks' gestational age and full‐term infants, respectively, during procedure | Mean PIPP/PIPP‐R during procedure ranged 8 to 11. | MD 2.58 lower (3.12 lower to 2.03 lower) | ‐ | 199 (3 RCTs) | ⊕⊕⊕⊝ Moderate 1 | Opioids probably reduce pain score assessed with the PIPP/PIPP‐R scale during the procedure compared to placebo. |
| Pain, assessed using the PIPP/PIPP‐R pain scale up to 30 min after procedure | Mean PIPP/PIPP‐R up to 30 min after procedure ranged 3 to 6. | MD 0.14 higher (0.17 lower to 0.45 higher) | ‐ | 123 (2 RCTs) | ⊕⊝⊝⊝ Very low 2 | The evidence is very uncertain about the effect of opioids on pain score assessed with the PIPP/PIPP‐R scale up to 30 min after the procedure compared to placebo. |
| Pain, assessed using the PIPP/PIPP‐R pain scale 1 to 2 hours after procedure | Mean PIPP/PIPP‐R 1 to 2 hours after procedure ranged 4 to 11. | MD −0.83 (2.42 lower to 0.75 higher) | ‐ | 54 (2 RCTs) | ⊕⊝⊝⊝ Very low 3 | The evidence is very uncertain about the effect of opioids on pain score assessed with the PIPP/PIPP‐R scale 1 to 2 hours after the procedure compared to placebo. |
| Pain, assessed using the DAN pain scale, ranging from 0 to 21, 1 to 2 hours after procedure | Mean DAN 1 to 2 hours after procedure was 5. | MD 0.2 lower (2.21 lower to 1.81 higher) | ‐ | 42 (1 RCT) | ⊕⊕⊝⊝ Low 4 | Opioids may result in little to no difference in pain score assessed with the DAN scale 1 to 2 hours after the procedure compared to placebo. |
| Pain, assessed using the NIPS, ranging from 0 to 7, during procedure | Mean NIPS during procedure ranged 5 to 6. | MD 1.97 lower (2.46 lower to 1.48 lower) | ‐ | 102 (2 RCTs) | ⊕⊕⊝⊝ Low 5 | Opioids may reduce NIPS during the procedure compared to placebo. |
| Any harms | ‐ | ‐ | ‐ | ‐ | ‐ | This outcome was not reported. |
| Episodes of bradycardia | Study population | RR 3.19
(0.14 to 72.69) RD 0.01, (−0.03 to 0.06) |
172 (3 RCTs) | ⊕⊝⊝⊝ Very low 6 | The evidence is very uncertain about the effect of opioids on episodes of bradycardia compared to placebo. | |
| 0 per 1000 (No events in the 3 RCTs) |
0 per 1000 (0 to 0) | |||||
| Episodes of apnea | Study population | RR 3.15
(1.08 to 9.16) RD 0.07 (0.01 to 0.14) NNTH = 14 |
199 (3 RCTs) | ⊕⊕⊝⊝ Low 7 | Opioids may result in an increase in episodes of apnea compared to placebo. | |
| 30 per 1000 | 95 per 1000 (33 to 278) | |||||
| Hypotension | Study population | ‐ | 88 (2 RCTs) | ⊕⊝⊝⊝ Very low 8 | The evidence is very uncertain about the effect of opioids on hypotension compared to placebo. | |
| See comment | See comment | |||||
| Parent satisfaction with care provided in the NICU (as measured by a validated instrument/tool)—not reported | ‐ | ‐ | ‐ | ‐ | This outcome was not reported. | This outcome was not reported. |
| *The risk in the intervention group (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). CI: confidence interval; DAN: Douleur Aiguë du Nouveau‐né; MD: mean difference; NICU: neonatal intensive care unit; NIPS: Neonatal Infant Pain Scale; NNTH: number needed to treat for an additional harmful outcome; OR: odds ratio; PIPP: Premature Infant Pain Profile; PIPP‐R: PIPP‐Revised; RCT: randomized controlled trial; RD: risk difference; RR: risk ratio | ||||||
| GRADE Working Group grades of evidence High certainty: we are very confident that the true effect lies close to that of the estimate of the effect. Moderate certainty: we are moderately confident in the effect estimate: the true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different. Low certainty: our confidence in the effect estimate is limited: the true effect may be substantially different from the estimate of the effect. Very low certainty: we have very little confidence in the effect estimate: the true effect is likely to be substantially different from the estimate of effect. | ||||||
1Downgraded one level for inconsistency (moderate heterogeneity, I² = 62%); not downgraded for imprecision (narrow CIs). 2Downgraded one level for inconsistency (substantial heterogeneity, I² = 85%) and two levels for imprecision (two small trials with low sample size; CIs overlapping no effect). 3Downgraded one level for study limitations (unclear risk of selection, performance, detection, and reporting bias) and two levels for imprecision (two small trials with low sample size; CIs overlapping no effect). 4Downgraded two levels for imprecision (one small trial with low sample size; CIs overlapping no effect). 5Downgraded one level for inconsistency (moderate heterogeneity, I² = 60%) and one level for imprecision (two small trials with low sample size; CIs not overlapping no effect). 6Downgraded one level for study limitations (unclear risk of selection bias in the informative study) and two levels for imprecision (three small trials with low sample size; CI overlapping no effect). 7Downgraded one level for study limitations (unclear risk of selection and reporting bias) and one level for imprecision (wide CIs). 8Downgraded one level for study limitations (unclear risk of selection and reporting bias) and two levels for imprecision (two small trials with no events).