Abstract
Background
Burst suppression in mechanically ventilated intensive care unit (ICU) patients is associated with increased mortality. However, the relative contributions of propofol use and critical illness itself to burst suppression; of burst suppression, propofol, and critical illness to mortality; and whether preventing burst suppression might reduce mortality, have not been quantified.
Methods
The dataset contains 471 adults from seven ICUs, after excluding anoxic encephalopathy due to cardiac arrest or intentional burst suppression for therapeutic reasons. We used multiple prediction and causal inference methods to estimate the effects connecting burst suppression, propofol, critical illness, and in-hospital mortality in an observational retrospective study. We also estimated the effects mediated by burst suppression. Sensitivity analysis was used to assess for unmeasured confounding.
Results
The expected outcomes in a “counterfactual” randomized controlled trial (cRCT) that assigned patients to mild versus severe illness are expected to show a difference in burst suppression burden of 39%, 95% CI [8–66]%, and in mortality of 35% [29–41]%. Assigning patients to maximal (100%) burst suppression burden is expected to increase mortality by 12% [7–17]% compared to 0% burden. Burst suppression mediates 10% [2–21]% of the effect of critical illness on mortality. A high cumulative propofol dose (1316 mg/kg) is expected to increase burst suppression burden by 6% [0.8–12]% compared to a low dose (284 mg/kg). Propofol exposure has no significant direct effect on mortality; its effect is entirely mediated through burst suppression.
Conclusions
Our analysis clarifies how important factors contribute to mortality in ICU patients. Burst suppression appears to contribute to mortality but is primarily an effect of critical illness rather than iatrogenic use of propofol.
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Code Availability
Code for the algorithm development, evaluation, and statistical analysis is open source with no restrictions and is available from https://github.com/mghcdac/burst_suppression_causal_inference.
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Funding
This work was supported by NIH-NINDS (1K23NS090900, 1R01NS102190, 1R01NS102574, 1R01NS107291) to MBW. This work was supported by SAGE Therapeutics to MBW, SZ, and ESR.
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HS, JH, HAN, MBW contributed to data analysis; HAN, JJ, JH, MT, FJ, SK, EB, JG, VMJ, MG, YS, MME, MS, and MBW contributed to data collection; JH, HS, HAN, SZ, and MBW contributed to study design; JH, HS, SZ, and MBW contributed to drafting initial manuscript; all co-authors contributed to manuscript revision.
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Hogan, J., Sun, H., Aboul Nour, H. et al. Burst Suppression: Causes and Effects on Mortality in Critical Illness. Neurocrit Care 33, 565–574 (2020). https://doi.org/10.1007/s12028-020-00932-4
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DOI: https://doi.org/10.1007/s12028-020-00932-4