Quantitative versus standard pupillary light reflex for early prognostication in comatose cardiac arrest patients: an international prospective multicenter double-blinded study

Mauro Oddo, Claudio Sandroni, Giuseppe Citerio, John-Paul Miroz, Janneke Horn, Malin Rundgren, Alain Cariou, Jean-François Payen, Christian Storm, Pascal Stammet, Fabio Silvio Taccone, Mauro Oddo, Claudio Sandroni, Giuseppe Citerio, John-Paul Miroz, Janneke Horn, Malin Rundgren, Alain Cariou, Jean-François Payen, Christian Storm, Pascal Stammet, Fabio Silvio Taccone

Abstract

Purpose: To assess the ability of quantitative pupillometry [using the Neurological Pupil index (NPi)] to predict an unfavorable neurological outcome after cardiac arrest (CA).

Methods: We performed a prospective international multicenter study (10 centers) in adult comatose CA patients. Quantitative NPi and standard manual pupillary light reflex (sPLR)-blinded to clinicians and outcome assessors-were recorded in parallel from day 1 to 3 after CA. Primary study endpoint was to compare the value of NPi versus sPLR to predict 3-month Cerebral Performance Category (CPC), dichotomized as favorable (CPC 1-2: full recovery or moderate disability) versus unfavorable outcome (CPC 3-5: severe disability, vegetative state, or death).

Results: At any time between day 1 and 3, an NPi ≤ 2 (n = 456 patients) had a 51% (95% CI 49-53) negative predictive value and a 100% positive predictive value [PPV; 0% (0-2) false-positive rate], with a 100% (98-100) specificity and 32% (27-38) sensitivity for the prediction of unfavorable outcome. Compared with NPi, sPLR had significantly lower PPV and significantly lower specificity (p < 0.001 at day 1 and 2; p = 0.06 at day 3). The combination of NPi ≤ 2 with bilaterally absent somatosensory evoked potentials (SSEP; n = 188 patients) provided higher sensitivity [58% (49-67) vs. 48% (39-57) for SSEP alone], with comparable specificity [100% (94-100)].

Conclusions: Quantitative NPi had excellent ability to predict an unfavorable outcome from day 1 after CA, with no false positives, and significantly higher specificity than standard manual pupillary examination. The addition of NPi to SSEP increased sensitivity of outcome prediction, while maintaining 100% specificity.

Keywords: Cardiac arrest; Neurological pupil index; Outcome; Prognostication; Pupillary reactivity; Pupillometry.

Conflict of interest statement

Mauro Oddo has received speaker honoraria from Neuroptics®. All the remaining authors declare no conflicts of interest related to this study.

Figures

Fig. 1
Fig. 1
Study flow chart. CPC Cerebral Performance Category
Fig. 2
Fig. 2
Distributions of Neurological Pupil index (NPi) during the first 3 days after cardiac arrest according to patient 3-month outcome. Scatterplots showing individual NPi values on days 1, 2 and 3 according to 3-month Cerebral Performance Category (CPC) outcome group, dichotomized as favorable (CPC 1–2; open circles) and unfavorable (CPC 3–5; filled squares)
Fig. 3
Fig. 3
Performance of Neurological Pupil index (NPi) versus quantitative pupillary light reflex (qPLR) to predict 3-month outcome (Cerebral Performance Category) at day 1 to 3 after cardiac arrest. Diagrams illustrate the area under the ROC curve (AUC) of qPLR (blue line) and NPi (grey line at days 1, 2 and 3; p for comparison of NPi AUC versus qPLR AUC. AUC of NPI to predict outcome at day 3 after cardiac arrest was significantly better than the AUC of qPLR [AUC 0.78 (0.72–0.83) vs. 0.71 (0.65–0.77) on day 3 (p  = 0.04)]

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