Sedation of mechanically ventilated adults in intensive care unit: a network meta-analysis

Abstract

Sedatives are commonly used for mechanically ventilated patients in intensive care units (ICU). However, a variety of sedatives are available and their efficacy and safety have been compared in numerous trials with inconsistent results. To resolve uncertainties regarding usefulness of these sedatives, we performed a systematic review and network meta-analysis. Randomized controlled trials comparing sedatives in mechanically ventilated ICU patients were included. Graph-theoretical methods were employed for network meta-analysis. A total of 51 citations comprising 52 RCTs were included in our analysis. Dexmedetomidine showed shorter MV duration than lorazepam (mean difference (MD): 68.7; 95% CI: 18.2-119.3 hours), midazolam (MD: 10.2; 95% CI: 7.7-12.7 hours) and propofol (MD: 3.4; 95% CI: 0.9-5.9 hours). Compared with dexmedetomidine, midazolam was associated with significantly increased risk of delirium (OR: 2.47; 95% CI: 1.17-5.19). Our study shows that dexmedetomidine has potential benefits in reducing duration of MV and lowering the risk of delirium.

Figure 1. PRISMA flow diagram for study inclusion.

Figure 2. Summary of risk of bias for included trials.

Figure 3. Network of comparators.

The nodes in the graph correspond to sedatives and edges display the observed treatment comparisons. The thickness of the edge is proportional to inverse standard error of random effects model comparing two treatments. For example, the dex-propofol comparison appears to be thick, indicating a small standard error for the effect size. Multi-arm studies were highlighted with blue color. For example, there is a study with three arms comprising midazolam, propofol and placebo. The triangle involving these three alternative treatments is filled with blue color.

Figure 4. Difference in duration of mechanical ventilation between comparators.

Dexmedetomidine was used as the reference.

Figure 5. Net heat plot highlights the inconsistency between specific direct and indirect evidence in the whole network.

The effect estimates in the row represents pooled effect of direct and indirect effects, and the effects in the column corresponds to the direct effect. There are gray squares in some cells, and the area size is proportional to the contribution of one design in a column that is estimated from direct comparison to an overall network estimate in a row. Also note there are different colors in the cells. After detaching the effect of column design, there will be a change in the inconsistency between direct and indirect estimates. Blue colors indicate an increase in the inconsistency between direct and indirect estimates, and warm colors indicate the opposite (the intensity of the color is proportional to the magnitude of change). The pairwise contrasts corresponding to designs of three-arm studies are marked by the symbol ‘_’ following the treatments of the design.

Figure 6. Odds of delirium in each sedative, as compared to that in dexmedetomidine group.