| Opioids compared to placebo or no treatment for neonates receiving mechanical ventilation |
|
Patient or population: neonates receiving mechanical ventilation
Setting: neonatal intensive care units in USA, UK, Germany, Sweden, Australia, China, Netherlands, Italy, Brazil
Intervention: opioids
Comparison: placebo or no treatment |
| Outcomes |
Anticipated absolute effects* (95% CI) |
Relative effect
(95% CI) |
№. of participants
(studies) |
Certainty of the evidence
(GRADE) |
Comments |
| Risk with placebo or no treatment |
Risk with opioids |
| Pain (PIPP) ‐ time window: ≥ 12 and < 48 hours after infusion |
Range 8.5 to 12.7 |
MD 0.98 points lower
(1.35 lower to 0.61 lower) |
‐ |
963
(3 RCTs) |
⊕⊝⊝⊝
VERY LOW |
Downgraded by 1 level for limitations in study design (unclear selective reporting in the 3 studies), by 1 level for high heterogeneity (difference between small and large beneficial effects), and by 2 level for imprecision of estimates (small sample size and wide confidence interval) |
| Duration of mechanical ventilation (days) |
Range 4.4 to 19 |
MD 0.23 days higher
(0.38 lower to 0.83 higher) |
‐ |
1259
(7 RCTs) |
⊕⊕⊕⊝
MODERATE |
Downgraded by 1 level for limitations in study design (unclear selective reporting in the 7 studies; unclear risk of bias in most domains in some studies) |
| Neonatal mortality |
Study population |
RR 1.12
(0.80 to 1.55) |
1189
(5 RCTs) |
⊕⊕⊕⊝
MODERATE |
Downgraded by 1 level for imprecision of estimates (wide confidence interval) |
| 101 per 1000 |
113 per 1000
(81 to 156) |
| Mortality to discharge |
Study population |
RR 0.99
(0.52 to 1.88) |
178
(4 RCTs) |
⊕⊕⊝⊝
LOW |
Downgraded by 1 level for limitations in study design (high or unclear risk of bias in most domains) and by 1 level for imprecision of estimates (wide confidence interval) |
| 156 per 1000 |
154 per 1000
(81 to 292) |
| Neurodevelopmental outcomes (18 to 24 months) |
Study population |
RR 2.00
(0.39 to 10.29) |
78
(1 RCT) |
⊕⊝⊝⊝
VERY LOW |
Downgraded by 2 levels for serious imprecision of estimates (1 small study) and indirectness (characteristics of this study) |
| 51 per 1000 |
103 per 1000
(20 to 528) |
| Neurodevelopmental outcomes (3 to 5 years) |
See comment |
See comment |
Not estimable |
Not reported |
Not estimable |
None of the studies reported on this outcome |
| Neurodevelopmental outcome (5 to 6 years) |
Study population |
RR 1.60
(0.56 to 4.56) |
95
(1 RCT) |
⊕⊝⊝⊝
VERY LOW |
Downgraded by 2 levels for serious imprecision of estimates (1 small study) and indirectness (characteristics of this study) |
| 121 per 1000 |
194 per 1000
(68 to 553) |
| *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; MD: mean difference; RCT: randomised controlled trial; PIPP: Premature Infant Pain Profile; 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. |
