Neurological Pupil Index and Intracranial Hypertension in Patients With Acute Brain Injury:A Secondary Analysis of the ORANGE Study

Matteo Petrosino, PhD; Elisa Gouvêa Bogossian, MD, PhD; Paola Rebora, PhD; et al

2024년 12월 9일

JAMA Neurol. 2025;82(2):176-184.

doi:10.1001/jamaneurol.2024.4189

Abstract

Importance 

Invasive intracranial pressure (ICP) is the standard of care in patients with acute brain injury (ABI) with impaired consciousness. The Neurological Pupil Index (NPi) obtained by automated pupillometry is promising for noninvasively estimating ICP.

Objective 

To evaluate the association between repeated NPi and invasive ICP values.

Design, Setting, and Participants 

This study is a secondary analysis of the Outcome Prognostication of Acute Brain Injury With the Neurological Pupil Index (ORANGE), a multicenter, prospective, observational study of patients with ABI performed from October 1, 2020, to May 31, 2022, with follow-up at 6 months after ABI. The ORANGE study was performed at neurologic intensive care units of tertiary hospitals in Europe and North America. In ORANGE, 514 adult patients receiving mechanical ventilatory support were admitted to the intensive care unit after ABI.

Exposure

Invasive ICP monitoring and automated pupillometry assessment every 4 hours during the first 7 days, considered as a standard of care.

Main Outcomes and Measures 

Association between ICP and NPi values over time, using bayesian joint models, with linear and logistic mixed-effects longitudinal submodels.

Results 

The study included 318 adult patients (median [IQR] age, 58 [43-69] years; 187 [58.8%] male) who required intensive care unit admission, intubation, and mechanical ventilatory support due to acute traumatic brain injury (n = 133 [41.8%]), intracerebral hemorrhage (n = 104 [32.7%]), or aneurysmal subarachnoid hemorrhage (n = 81 [25.5%]) and had automatic infrared pupillometry used as part of the standard evaluation practice and ICP monitoring. A total of 8692 ICP measurements were collected, with a median (IQR) of 31 (18-37) evaluations per patient. The median (IQR) NPi and ICP for the study population were 4.1 (3.5-4.5) and 10 (5-14) mm Hg, respectively. In a linear mixed model, the mean change in the NPi value, as a continuous variable, was −0.003 (95% credible interval [CrI], −0.006 to 0.000) for each 1-mm Hg ICP increase. No significant association between ICP and abnormal NPi (<3; odds ratio, 1.01; 95% CrI, 0.99-1.03) or absent NPi (0; odds ratio, 1.03; 95% CrI, 0.99-1.06) was observed.

Conclusions and Relevance 

Although an abnormal NPi could indicate brainstem dysfunction, in this large and heterogeneous population of patients, NPi values were not significantly associated overall with ICP values. Repeated NPi measurements may not be a sufficient replacement for invasive monitoring.

Trial Regristration

ClinicalTrials.gov Identifier: NCT04490005

Key Points

Question  Is there an association between paired Neurological Pupil Index (NPi) assessed by automated pupillometry and invasive intracranial pressure (ICP) values in patients with acute brain injury?

Findings  This preplanned secondary analysis of the observational, multicenter ORANGE study included 318 patients and did not find any clinically significant association between ICP and NPi values assessed as continuous variables. There was also no clinically significant association between ICP as a continuous variable and dichotomized abnormal NPi values or between ICP and absent NPi.

Meaning  In this study on patients with subarachnoid hemorrhage, traumatic brain injury, and intracerebral hemorrhage, repeated NPi measurements are insufficient to replace invasive monitoring.

요약

• 소개 : 급성 뇌손상(ABI) 환자에서 두개내압(ICP) 모니터링은 필수적이다. 자동화 동공계(Automated Pupillometry)를 이용한 신경학적 동공 지수(NPi)는 비침습적으로 ICP를 추정할 수 있는 가능성이 있다. 본 연구는 반복 측정된 NPi와 ICP 간의 연관성을 분석하여 NPi의 ICP 모니터링 대체 가능성을 평가하는 것을 목표로 한다.

• 방법 : ORANGE 연구의 2차 분석으로, 2020년 10월부터 2022년 5월까지 유럽 및 북미의 3차 병원에서 진행되었다. 기계적 환기를 받는 ABI 환자 514명 중 318명을 대상으로, 입원 후 첫 7일 동안 4시간마다 ICP와 NPi를 측정하였다. Bayesian joint 모델과 혼합 효과 모델을 통해 ICP와 NPi 간의 연관성을 평가하였다.

• 결과 : ICP의 중간값은 10 mmHg, NPi의 중간값은 4.1로 확인되었다. ICP가 1 mmHg 증가할 때 NPi는 평균적으로 0.003만큼 감소했으나 임상적으로 유의하지 않았다. 비정상 NPi(<3) 또는 NPi 소실(0)과 ICP 간의 유의한 관련성은 발견되지 않았다.

  
  

• 결론 및 의의 : ABI 환자에서 반복적인 NPi 측정은 뇌간 기능 이상을 나타낼 수는 있으나, ICP 값과의 유의한 연관성은 확인되지 않았다. 비침습적 NPi 측정은 ICP를 대체할 수 있는 충분한 신뢰성을 제공하지 않으며, ABI 환자에서 침습적 ICP 모니터링이 여전히 필수적이다.