Validating quantitative pupillometry thresholds for neuroprognostication after out-of-hospital cardiac arrest. A predefined substudy of the Blood Pressure and Oxygenations Targets After Cardiac Arrest (BOX)-trial,Intensive Care Medicine

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Validating quantitative pupillometry thresholds for neuroprognostication after out-of-hospital cardiac arrest. A predefined substudy of the Blood Pressure and Oxygenations Targets After Cardiac Arrest (BOX)-trial
Intensive Care Medicine ( IF 27.1 ) Pub Date : 2024-08-20 , DOI: 10.1007/s00134-024-07574-6
Benjamin Nyholm ₁ , Johannes Grand ₁ , Laust E R Obling ₁ , Christian Hassager _{1,

2} , Jacob Eifer Møller _{1,

3,

4} , Henrik Schmidt _{4,

5} , Marwan H Othman ₆ , Daniel Kondziella _{2,

6} , Janneke Horn ₇ , Jesper Kjaergaard _{1,

2}

Affiliation

Purpose

Out-of-hospital cardiac arrest (OHCA) survivors face significant risks of complications and death from hypoxic–ischemic brain injury leading to withdrawal of life-sustaining treatment (WLST). Accurate multimodal neuroprognostication, including automated pupillometry, is essential to avoid inappropriate WLST. However, inconsistent study results hinder standardized threshold recommendations. We aimed to validate proposed pupillometry thresholds with no false predictions of unfavorable outcomes in comatose OHCA survivors.

Methods

In the multi-center BOX-trial, quantitative measurements of automated pupillometry (quantitatively assessed pupillary light reflex [qPLR] and Neurological Pupil index [NPi]) were obtained at admission (0 h) and after 24, 48, and 72 h in comatose patients resuscitated from OHCA. We aimed to validate qPLR < 4% and NPi ≤ 2, predicting unfavorable neurological conditions defined as Cerebral Performance Category 3–5 at follow-up. Combined with 48-h neuron-specific enolase (NSE) > 60 μg/L, pupillometry was evaluated for multimodal neuroprognostication in comatose patients with Glasgow Motor Score (M) ≤ 3 at ≥ 72 h.

Results

From March 2017 to December 2021, we consecutively enrolled 710 OHCA survivors (mean age: 63 ± 14 years; 82% males), and 266 (37%) patients had unfavorable neurological outcomes. An NPi ≤ 2 predicted outcome with 0% false-positive rate (FPR) at all time points (0–72 h), and qPLR < 4% at 24–72 h. In patients with M ≤ 3 at ≥ 72 h, pupillometry thresholds significantly increased the sensitivity of NSE, from 42% (35–51%) to 55% (47–63%) for qPLR and 50% (42–58%) for NPi, maintaining 0% (0–0%) FPR.

Conclusion

Quantitative pupillometry thresholds predict unfavorable neurological outcomes in comatose OHCA survivors and increase the sensitivity of NSE in a multimodal approach at ≥ 72 h.

中文翻译：

验证院外心脏骤停后神经预后的定量瞳孔阈值。心脏骤停后血压和氧合目标（BOX）试验的预定义子研究

目的

院外心脏骤停（OHCA）幸存者面临缺氧缺血性脑损伤导致停用生命维持治疗（WLST）的并发症和死亡的重大风险。准确的多模态神经预后，包括自动瞳孔测量，对于避免不适当的 WLST 至关重要。然而，不一致的研究结果阻碍了标准化阈值推荐。我们旨在验证提出的瞳孔测量阈值，而不会对昏迷 OHCA 幸存者的不良结果进行错误预测。

方法

在多中心 BOX 试验中，在入院（0 h）和 24 、 48 和 72 小时后，从 OHCA 复苏的昏迷患者获得自动瞳孔测量（定量评估瞳孔光反射 [qPLR] 和神经瞳孔指数 [NPi]）的定量测量。我们旨在验证 qPLR < 4% 和 NPi ≤ 2，预测在随访中定义为脑性能类别 3-5 的不利神经系统状况。结合 48 h 神经元特异性烯醇化酶（NSE） > 60 μg/L，评估 ≥ 72 h 时格拉斯哥运动评分（M） ≤ 3 的昏迷患者的多模式神经预后。

结果

从 2017 年 3 月到 2021 年 12 月，我们连续招募了 710 名 OHCA 幸存者（平均年龄： 63 ± 14 岁;82% 为男性），266 名（37%）患者出现不良神经系统结局。NPi ≤ 2 预测结果，所有时间点（0-72 小时）的假阳性率（FPR）为 0%，24-72 小时的 qPLR < 为 4%。在 ≥ 72 小时 M ≤ 3 的患者中，瞳孔测量阈值显着增加了 NSE 的敏感性，qPLR 从 42% （35-51%）增加到 55% （47-63%），NPi 从 50% （42-58%）保持 0% （0-0%） FPR。