Is the bispectral index monitoring protective against postoperative cognitive decline? A systematic review with meta-analysis

Abstract

Background: Several studies have suggested that monitoring the depth of anaesthesia might prevent the development of postoperative cognitive decline. We aimed to conduct a meta-analysis to investigate the effects of bispectral index (BIS) monitoring in anaesthesia.

Methods: We searched in six major electronic databases. Trials were included if they discussed anaesthesia with and without BIS monitoring or low (<50) and high (≥50) BIS levels and which measured the risk of postoperative delirium (POD) and/or postoperative cognitive dysfunction (POCD).

Results: We included fourteen studies in the systematic review, eight of which were eligible for meta-analysis. BIS proved to be protective against POD at 1 day postoperatively in a cohort of 2138 patients (16.1% vs. 22.8% for BIS vs. no BIS groups, respectively; relative risk [RR] 0.71; 95% confidence interval [CI] 0.59 to 0.85, without significant between-study heterogeneity I2 = 0.0%, P = 0.590). The use of BIS was neutral for POCD at 1 week but protective for POCD at 12 weeks (15.8% vs. 18.8% for BIS vs. no BIS groups, respectively; RR = 0.84, CI: 0.66 to 1.08), without significant between-study heterogeneity (I2 = 25.8%, P = 0.260). The neutral association at 1 week proved to be underpowered with trial sequential analysis. In the comparison of low BIS versus high BIS, the incidence of POD at 1 day was similar in the groups.

Conclusion: Our findings suggest a protective effect of BIS compared to not using BIS regarding the incidence of POD at 1 day and POCD at 12 weeks. However, limitations of the evidence warrant further investigation to identify those groups of patients by age, comorbid conditions and other individual variables who would benefit the most from the use of BIS monitoring.

Fig 1. Flow chart of study selection.

Fig 2. Risk of bias table.

RCT: randomised controlled trial; "+": low risk of bias; "?": unclear risk of bias; "−": high risk of bias.

Fig 3. Risk of bias graph.

Fig 4. Risk of POD at 1 day with BIS vs. without BIS monitoring.

POD: postoperative delirium; BIS: bispectral index; RR: relative risk; Cl: confidence interval.

Fig 5. Risk of POCD at 1 and 12 weeks with BIS vs. without BIS monitoring.

POCD: postoperative cognitive dysfunction; BIS: bispectral index; RR: relative risk; Cl: confidence interval.

Fig 6. Trial sequential analysis of data in the BIS vs. no BIS monitoring anaesthesia comparison for the outcome of POCD.

Trial sequential analysis (TSA) is a random effect-based meta-analytical model to estimate the "required information size"; in other words, the required meta-analytical sample size allowing us to draw a confident conclusion. Each dot on the Z-curve represents a new piece of information, the results of a new randomised study (a total of three studies were used in our case). If the Z-curve crosses the futility boundary, the intervention has no significant effect on the outcome and the results are unlikely to change if further studies are added. If the Z-curve, crosses the significance boundaries, the intervention has a significant effect on the outcome. In our case, neither the conventional significance boundary nor trial sequential significance boundary was crossed by the cumulative Z-curve indicating that the meta-analytical sample size (1985 patients) is insufficient to draw a confident conclusion: further studies are needed until the "required information size" (6461 patients) is reached. BIS: bispectral index; POCD: postoperative cognitive dysfunction.

Fig 7. Risk of POD at 1, 2 and 5 days with low BIS vs. high BIS monitoring.

POD: postoperative delirium; BIS: bispectral index; RR: relative risk; Cl: confidence interval.