Burst Suppression: Causes and Effects on Mortality in Critical Illness
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ORIGINAL WORK
Burst Suppression: Causes and Effects on Mortality in Critical Illness Jacob Hogan1,2†, Haoqi Sun1†, Hassan Aboul Nour1,6†, Jin Jing1,3, Mohammad Tabaeizadeh1, Maryum Shoukat1, Farrukh Javed1, Solomon Kassa1, Muhammad M. Edhi1,4, Elahe Bordbar1, Justin Gallagher1, Valdery Moura Junior1, Manohar Ghanta1, Yu‑Ping Shao1, Oluwaseun Akeju5, Andrew J. Cole1, Eric S. Rosenthal1‡, Sahar Zafar1‡ and M. Brandon Westover1*‡ © 2020 Springer Science+Business Media, LLC, part of Springer Nature and Neurocritical Care Society
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 suppres‑ sion; 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. Keywords: Burst suppression, Mortality, Critical care, Electroencephalography
*Correspondence: [email protected] † Jacob Hogan, Haoqi Sun, and Hassan Aboul Nour have contributed equally as co-first authors. ‡ Eric S. Rosenthal, Sahar Zafar, and M. Brandon Westover have contributed equally as co-senior authors. 1 Department of Neurology, Massachusetts General Hospital, 55 Fruit Street, Boston, MA 02114, USA Full list of author information is available at the end of the article
Introduction Burst suppression is a pattern of brain activity where the electroencephalogram (EEG) is intermittently interrupted by “s
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