• Jacob Hogan, Haoqi Sun, Aboul NourHassanHDepartment of Neurology, Massachusetts General Hospital, 55 Fruit Street, Boston, MA, 02114, USA.Department of Neurology, Henry Ford Hospital, Detroit, MI, USA., Jin Jing, Mohammad Tabaeizadeh, Maryum Shoukat, Farrukh Javed, Solomon Kassa, Muhammad M Edhi, Elahe Bordbar, Justin Gallagher, JuniorValdery MouraVMDepartment of Neurology, Massachusetts General Hospital, 55 Fruit Street, Boston, MA, 02114, USA., Manohar Ghanta, Yu-Ping Shao, Oluwaseun Akeju, Andrew J Cole, Eric S Rosenthal, Sahar Zafar, and M Brandon Westover.
• Department of Neurology, Massachusetts General Hospital, 55 Fruit Street, Boston, MA, 02114, USA.
• Neurocrit Care. 2020 Oct 1; 33 (2): 565-574.

BackgroundBurst 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.MethodsThe 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.ResultsThe 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.ConclusionsOur 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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