Abstract Funding Acknowledgements Type of funding sources: Private grant(s) and/or Sponsorship. Main funding source(s): Novo Nordisk Foundation Background Quantitative pupillometry has been implemented in resuscitation guidelines as part of multimodal prognostication in comatose out-of-hospital cardiac arrest (OHCA) patients. Post-resuscitation intensive care allows for different blood-pressure and oxygen targets, but evidence on the implication of these targets on prognostication is limited. Purpose To assess the impact of different blood-pressure and oxygen targets in resuscitated OHCA patients on the prognostic ability of the quantitatively assessed percentage reduction of pupillary size (qPLR, %) and the neurological pupil index (NPi, 0-5). Methods The BOX-trial is a multicenter, double-blind, randomized trial, comparing low (63 mm Hg) versus high (77 mm Hg) mean arterial blood-pressure targets and restrictive (9 to 10 kPa) versus liberal (13 to 14 kPa) partial pressure of arterial oxygen targets in comatose survivors of OHCA. In this predefined, prospective substudy, quantitative pupillometry measurements were obtained from consecutively enrolled patients at 0, 24, 48, 72, 96, and 120 hours after OHCA (t0-t120). The prognostic performance of qPLR and NPi for high and low blood-pressure groups, and liberal and restrictive oxygen target groups were illustrated through the area under the receiver operating characteristic (ROC) curves (AUC). The time point achieving the highest AUC was used for further analyses. AUCs were compared with DeLong’s test. Results The highest AUC for qPLR and NPi were achieved for measurements made 48 hours after OHCA. qPLR produced AUC at 0.79 [95%CI 0.73-0.85] and 0.81 [95%CI 0.75-0.86] for high and low blood-pressure groups, and 0.79 [95%CI 0.73-0.85] and 0.80 [95%CI 0.74-0.86] for liberal and restrictive oxygen target groups, respectively (Fig 1). For NPi AUC were 0.79 [95%CI 0.73-0.85] and 0.78 [95%CI 0.72-0.84] in high and low blood-pressure groups, and 0.77 [95%CI 0.71-0.83] and 0.80 [95%CI 0.75-0.86] in liberal and restrictive oxygen target groups, respectively (Fig 2). No significant difference between any groups, for either blood-pressure or oxygen targets, was found. Conclusion Prognostic value of quantitative pupillometry for predicting outcome in resuscitated OHCA patients was high and consistent across different blood-pressure and oxygen level targets.