Table 3.
Bayesian NMA Summary of Findings—delirium occurrence.
| Patient or population: critically ill adults, includes both non-ventilated and mechanically ventilated patients. | |||||||
| Interventions: any interventions and strategies for sedation titration (e.g., protocolized and interruption). | |||||||
| Comparator (reference): placebo. | |||||||
| Outcome: delirium occurrence. | |||||||
| Setting(s): mixed intensive care unit settings |
| Total studies: 38 Total participants: 11,993 |
Relative effect * (95% CrI) | Anticipated absolute effect (95% CrI) | Certainty of the evidence | Number of participants (trials) | Ranking*** (95% CrI) | ||
|---|---|---|---|---|---|---|---|
| Placebo | Intervention | Risk difference** | |||||
| Alpha2 agonist vs placebo |
OR 0.43 (0.21–0.85) NMA estimate |
278 per 1000 (147/528 based on 5 trials) | 163 per 1000 (86/527 based on 5 trials) | 136 fewer per 1000 (from 204 to 30 fewer) |
⊕ ⊕ ⊕ ◯ Moderate Due to inconsistency2 |
Direct evidence: 1055 (5 trials) | 2.73 (1–5) |
| Antipsychotics vs placebo |
OR 0.63 (0.36–1.04) NMA estimate |
309 per 1000 (375/1199 based on 8 trials) | 301 per 1000 (473/1577 based on 8 trials) | 91 fewer per 1000 (from 170 fewer to 9 more) |
⊕ ⊕ ◯◯ Low Due to imprecision3, and inconsistency2 |
Direct evidence: 2776 (8 trials) | 4.80 (1–9) |
| Melatonin/MRA vs placebo |
OR 0.66 (0.19–2.50) NMA estimate |
186 per 1000 (21/113 based on 2 trials) |
125 per 1000 (14/112 based on 2 trials) |
55 fewer per 1000 (from 144 fewer to 178 more) |
⊕ ⊕ ◯◯ Low Due to imprecision3 and inconsistency2 |
Direct evidence: 225 (2 trials) | 5.22 (1–11) |
| Sedation interruption vs placebo |
OR 0.42 (0.14–1.22) NMA estimate |
330 per 1000 1 | No head-to-head comparison with placebo | 157 fewer per 1000 (from 265 fewer to 46 more) |
⊕ ◯◯◯ Very low Due to imprecision3, indirectness4, inconsistency5 and risk of bias |
No direct evidence. Indirect evidence only | 2.81 (1–7) |
| Protocolized sedation vs placebo |
OR 0.54 (0.21–1.40) NMA estimate |
330 per 1000 1 | No head-to-head comparison with placebo | 119 fewer per 1000 (from 238 fewer to 77 more) |
⊕ ◯◯◯ Very low Due to imprecision3, indirectness4, inconsistency6 and risk of bias |
No direct evidence. Indirect evidence only | 4.27 (1–8) |
| Opioid + benzodiazepine vs placebo |
OR 0.54 (0.12–2.54) NMA estimate |
330 per 1000 1 | No head-to-head comparison with placebo | 119 fewer per 1000 (from 275 fewer to 225 more) |
⊕ ◯◯◯ Very low Due to imprecision3, Serious indirectness7, inconsistency8 and risk of bias |
No direct evidence. Indirect evidence only | 4.36 (1–10) |
| Propofol vs placebo |
OR 1.15 (0.32–4.13) NMA estimate |
330 per 10001 | No head-to-head comparison with placebo | 31 more per 1000 (from 192 fewer to 341 more) |
⊕ ◯◯◯ Very low Due to imprecision3, indirectness4, and inconsistency5 |
No direct evidence. Indirect evidence only | 7.77 (2–11) |
| Opioid vs placebo |
OR 1.26 (0.24–6.56) NMA estimate |
330 per 1000 1 | No head-to-head comparison with placebo | 53 more per 1000 (from 222 fewer to 434 more) |
⊕ ◯◯◯ Very low Due to imprecision3, serious indirectness9, inconsistency6 |
No direct evidence. Indirect evidence only | 7.91 (2–11) |
| Opioid (short acting) vs placebo |
OR 1.54 (0.34 to 7.07) NMA estimate |
330 per 1000 1 | No head-to-head comparison with placebo |
102 more per 1000 (from 188 fewer to 447 more) |
⊕ ◯◯◯ Very low Due to Imprecision3, Indirectness4, and Inconsistency5 |
No direct evidence. Indirect evidence only |
8.73 (3–11) |
| Benzodiazepine vs placebo |
OR 2.02 (0.65–6.40) NMA estimate |
330 per 1000 1 | No head-to-head comparison with placebo | 169 more per 1000 (from 86 fewer to 429 more) |
⊕ ◯◯◯ Very low Due to imprecision3, indirectness4, inconsistency5 |
No direct evidence. Indirect evidence only | 9.87 (6–11) |
| Placebo | Reference comparator | – | – | – | – | 7.53 (4–10) | |
GRADE Working Group grades of evidence (or certainty in the 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
Abbreviations
CrI credible interval, OR odds ratio
NMA-SoF table definitions
*Network meta-analysis estimates are reported as odds ratio. CrI: credible interval (rather than confidence interval), since a Bayesian network meta-analysis has been conducted
**Anticipated absolute effect: risk difference is calculated based on the control group risk and the estimated odds ratio
***Median and credible intervals are presented. Rank statistics is defined as the probabilities that a treatment out of n treatments in a network meta-analysis is the best, the second, the third and so on until the least effective treatment
Explanatory footnotes
1Given that there were no head-to-head trials for these comparisons, the control group rate is based on the placebo arm of a large, randomized control trial (Boogaard et al. 2018, antipsychotic vs placebo)
2Inconsistency: due to heterogeneity in the direct comparison
3Imprecision: due to wide credible intervals in the OR estimate
4Indirectness: only indirect evidence available (through one degree of intermediary, alpha2 agonist)
5Inconsistency: due to heterogeneity in the direct comparison of alpha2 agonist vs placebo
6Inconsistency: due to heterogeneity in the direct comparison of alpha2 agonist vs placebo and the direct comparison of protocolized vs alpha2 agonist
7Serious indirectness: only indirect evidence available (through two degrees of intermediaries, alpha2 agonist and benzodiazepine)
8Inconsistency: due to heterogeneity in the direct comparison of alpha2 agonist vs placebo and the direct comparison of benzodiazepine vs alpha2 agonist
9Serious indirectness: only indirect evidence available (through three degrees of intermediaries, interruption / opioid (short acting), alpha2 agonist, and benzodiazepine)