Neurological Pupil Index Research Articles

The prognostic role of Neurologic Pupil Index in COVID-19 patients: a retrospective study.

Neurological complications have been observed in approximately 30% of hospitalized COVID-19 patients. The aim of this study was to evaluate whether early assessment of the Neurological Pupil Index (NPiTM) derived from an automated pupillometry could predict mortality in critically ill COVID-19 patients. Retrospective cohort study of adult critically ill COVID-19 patients admitted to the intensive care unit of a University Hospital; patients without NPi measurement were excluded. The worst NPi (i.e. lowest value from one eye) was collected daily and then computed over the first five days of assessment. Mortality was assessed at hospital discharge. The secondary endpoint involved assessing differences in neurological assessments between patients who developed neurological complications and those who did not. A total of 217 patients were included over the study period (median age 61 [50-68] years), 70% were males. A total of 97 patients (45%) died during the hospital stay. Among all patients, 35 (16%) experienced neurological complications. Non-survivors showed significantly a lower overall NPi (3.0 [2.0-4.1] vs. 3.4 [2.7-4.2]; P=0.04) than survivors. At multivariate logistic regression NPi was not significantly associated with in-hospital mortality. Moreover, no differences in different NPi measurements were observed between patients with and without neurological complications. In this study, NPi values were not independent predictor of mortality and neurological complications in critically ill COVID-19 patients.

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

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

Dynamically Normalized Pupillometry for Detecting Delayed Cerebral Ischemia After Aneurysmal Subarachnoid Hemorrhage.

Delayed cerebral ischemia (DCI) is a major driver of morbidity after aneurysmal subarachnoid hemorrhage (aSAH). Quantitative pupillometry has been shown to be of prognostic value after acute neurological injury. However, the evidence for the use of pupillometric features for the detection of DCI has been conflicting. The aim of this study was to investigate the prognostic value of frequent pupillometric monitoring for DCI detection. Observational cohort study from a prospective aSAH registry. Tertiary referral center. Adult patients with confirmed aSAH admitted to the ICU between March 2019 and December 2023. None. One hundred fourteen patients were included, of which 31 (27.2%) suffered from DCI. All patients underwent frequent pupillometry (every 3 hr). We determined the absolute value of the neurological pupil index (NPi) and constriction velocity (CV), and their value normalized to the maximal recorded value between the admission and the pupillometry measure to account for personalized baselines. The association between pupillometry values and the occurrence of DCI within 6-24 hours was investigated. Normalized CV had the best discriminative performance to identify DCI within 8 hours, with an area under the receiver operating characteristic curve of 0.82 (95% CI, 0.69-0.91). NPi, as well as non-normalized metrics, were not significantly associated with DCI. Normalized CV has a clinically and statistically significant association with the occurrence of DCI after aSAH. Frequent quantitative pupillometry could improve the multimodal monitoring of patients after aSAH with the goal of improving the identification of patients likely to benefit from therapeutic interventions.

Automated Pupillometry Is Able to Discriminate Patients with Acute Stroke from Healthy Subjects: An Observational, Cross-Sectional Study.

Automated pupillometry (AP) is a handheld, non-invasive tool that is able to assess pupillary light reflex dynamics and is useful for the detection of intracranial hypertension. Limited evidence is available on acute ischemic stroke (AIS) patients. The primary objective was to evaluate the ability of AP to discriminate AIS patients from healthy subjects (HS). Secondly, we aimed to compute a predictive score for AIS diagnosis based on clinical, demographic, and AP variables. We included 200 consecutive patients admitted to a comprehensive stroke center who underwent AP assessment through NPi-200 (NeurOptics®) within 72 h of stroke onset and 200 HS. The mean values of AP parameters and the absolute differences between the AP parameters of the two eyes were considered in the analyses. Predictors of stroke diagnosis were identified through univariate and multivariate logistic regressions; we then computed a nomogram based on each variable's β coefficient. Finally, we developed a web app capable of displaying the probability of stroke diagnosis based on the predictive algorithm. A high percentage of pupil constriction (CH, p < 0.001), a low constriction velocity (CV, p = 0.002), and high differences between these two parameters (p = 0.036 and p = 0.004, respectively) were independent predictors of AIS. The highest contribution in the predictive score was provided by CH, the Neurological Pupil Index, CV, and CV absolute difference, disclosing the important role of AP in the discrimination of stroke patients. The results of our study suggest that AP parameters, and in particular, those concerning pupillary constriction, may be useful for the early diagnosis of AIS.

Measurement of dynamic pupillometry parameters in adult Indian population.

To determine normative dynamic pupillometry data in healthy Indian adults and to investigate the effect of age on various pupillary parameters. Pupillometry measurements were obtained on healthy participants using an automatic dynamic pupillometry device, the NPi-200 (NeurOptics Inc., Irvine, CA, USA). Various measurements, including neurologic pupil index (NPi), resting pupil size (Size), minimum pupil diameter (MIN), percentage change in pupil size (CH), constriction velocity (CV), maximum constriction velocity (MCV), latency (LAT), and dilatation velocity (DV), were obtained in routine clinical settings and analyzed statistically for change with age. A total of 470 participants (470 eyes) were analyzed. Mean NPi was 4.31 ± 0.31, Size was 4.38 ± 0.80 mm, MIN was 2.87 ± 0.49 mm, CH was 34.67 ± 4.15%, CV was 2.74 ± 0.68 mm/s, MCV was 4.16 ± 0.98 mm/s, LAT was 0.23 ± 0.02 s, and DV was 1.13 ± 0.25 mm/s. NPi and LAT were positively correlated (P < 0.01), whereas Size, MIN, CH, CV, MCV, and DV were negatively correlated with age (P < 0.01). No statistically significant difference was observed between males and females. The study offers normative data on dynamic pupillometry parameters across various age groups within a healthy Indian population, which would serve as a reference for future studies in diverse clinical scenarios. It also elucidates that age significantly influences values in the NPi algorithm.

Influence of Sevoflurane on the Neurological Pupil Index in Surgical and Critically Ill Patients: A Pilot Study.

The aim of this study was to compare the effects of sevoflurane on the neurologic pupil index (NPi), obtained by means of automated pupillometry, between intensive care unit (ICU) and surgical patients. This was a prospective single-center study conducted between December 2021 and February 2023. The eligible population comprised all patients undergoing general anesthesia (GA) for visceral surgery (VS) or neurosurgery (NS) and ICU patients receiving inhaled sevoflurane, according to the decision of the treating physician. The NPi measurements were conducted before GA (T0), after induction (T1), after the initiation of sevoflurane (T2), and at the point of discontinuation of sevoflurane (T3). A total of 41 VS, 16 NS, and 22 ICU patients (out of which, 12 had a brain injury) were included. In the VS and NS groups, there was a significant decrease in the NPi over time, which remained within normal ranges. The NPi values decreased over time in the ICU group after sevoflurane administration. At T2, the NPi values were lower in the ICU group compared to the other groups. Lower NPi values were observed in the ICU patients with a brain injury compared to other patients. The administration of inhaled sevoflurane was associated with a significant reduction in the NPi values of the ICU patients with a concomitant brain injury.

Prediction of neurocritical care intensity through automated infrared pupillometry and transcranial doppler in blunt traumatic brain injury: the NOPE study

PurposeThis pilot study aimed to determine the capacity of automated infrared pupillometry (AIP) alone and in combination with transcranial doppler (TCD) on admission to rule out need for intense neuroAQ2 critical care (INCC) in severe traumatic brain injury (TBI).MethodsIn this observational pilot study clinicians performed AIP and TCD measurements on admission in blunt TBI patients with a Glasgow Coma Score (GCS) < 9 and/or motor score < 6. A Neurological Pupil index (NPi) < 3, Pulsatility Index (PI) > 1,4 or diastolic blood flow velocity (dV) of < 20 cm/s were used to rule out the need for INCC (exceeding the tier 0 Seattle Consensus Conference). The primary outcome was the negative likelihood ratio (nLR) of NPi < 3 alone or in combination with TCD to detect need for INCC.ResultsA total of 69 TBI patients were included from May 2019 to September 2020. Of those, 52/69 (75%) median age was 45 [28–67], median prehospital GCS of 7 [5–8], median Injury Severity Scale of 13.0 [6.5–25.5], median Marshall Score of 4 [3–5], the median Glasgow Outcome Scale at discharge was 3 [1–5]. NPi < 3 was an independent predictor of INCC. NPi demonstrated a nLR of 0,6 (95%CI 0.4–0.9; AUROC, 0.65, 95% CI 0.51–0.79), a combination of NPi and TCD showed a nLR of 0.6 (95% CI 0.4–1.0; AUROC 0.67 95% CI 0.52–0.83) to predict INCC.ConclusionThis pilot study suggests a possible useful contribution of NPi to determine the need for INCC in severe blunt TBI patients on admission.

Diurnal variation in quantitative pupillary reactivity in large hemispheric stroke

Background: Pupillary light reflex (PLR) assessment is an important neurological examination reflecting neurological deterioration in severe stroke cases. This study investigated the impact of diurnal variation in the PLR using quantitative pupillometry in stable patients with large hemispheric stroke.Methods: We included 35 patients with large hemispheric stroke without neurological worsening, who were admitted to the neurological intensive care unit between April 2017 and November 2021. Quantitative pupillometry was performed every 4 hours. Pupillometer parameters of maximum pupil size, percentage of constriction (%CH), latency (LAT), constriction velocity (CV), dilation velocity (DV), maximum constriction velocity (MCV), and neurological pupil index (NPi) score were recorded. We evaluated changes in the pupillometer parameters over time using linear mixed model analysis.Results: The diurnal variations revealed that the following parameters were significantly higher at 04:00 than at 20:00: maximum pupil size (right [Rt]: 3.59 vs. 3.21 mm, P&lt;0.001; left [Lt]: 3.51 vs. 3.18 mm, P&lt;0.001), %CH (Rt: 31.48 vs. 25.72, P&lt;0.001; Lt: 31.42 vs. 24.98, P&lt;0.001), CV (Rt: 1.97 vs. 1.68 mm/sec, P&lt;0.001; Lt: 1.98 vs. 1.65 mm/sec, P&lt;0.001), and DV (Rt: 0.97 vs. 0.84 mm/sec, P&lt;0.001; Lt: 0.94 vs. 0.82 mm/sec, P=0.001). However, no significant diurnal variations were observed in the NPi values. Conclusion: Pupillary dynamics based on quantitative pupillometer parameters, including the NPi, demonstrated diurnal variations over 24 hours in large hemispheric stroke patients without neurological worsening. However, all changes in the pupillometer parameters were within normal ranges.

The use of quantitative pupillometry in brain death determination: preliminary findings

PurposeQuantitative pupillometry (QP) has been increasingly applied in neurocritical care as an easy-to-use and reliable technique for evaluating the pupillary light reflex (PLR). Here, we report our preliminary findings on using QP for clinical brain death (BD) determination.MaterialsThis retrospective study included 17 patients ≥ 18 years (mean age, 57.3 years; standard deviation, 15.8 years) with confirmed BD, as defined by German Guidelines for the determination of BD. The PLR was tested using the NPi®-200 Pupillometer (Neuroptics, Laguna Hill, USA), a handheld infrared device automatically tracking and analyzing pupil dynamics over 3 s. In addition, pupil diameter and neurological pupil index (NPi) were also evaluated.ResultsIntracerebral bleeding, subarachnoid hemorrhage, and hypoxic encephalopathy were the most prevalent causes of BD. In all patients, the NPi was 0 for both eyes, indicating the cessation of mid-brain function. The mean diameter was 4.9 mm (± 1.3) for the right pupil and 5.2 mm (±1.2) for the left pupil.ConclusionsQP is a valuable tool for the BD certification process to assess the loss of PLR due to the cessation of brain stem function. Furthermore, implementing QP before the withdrawal of life-sustaining therapy in brain-injured patients may reduce the rate of missed organ donation opportunities. Further studies are warranted to substantiate the feasibility and potential of this technique in treating patients and identify suitable candidates for this technique during the BD certification process.

Neurological pupil index as a screening tool for intracranial hypertension: A systematic review and meta-analysis

Neurological pupil index as a screening tool for intracranial hypertension: A systematic review and meta-analysis

A smartphone pupillometry tool for detection of acute large vessel occlusion

ObjectivesPupillary light reflex (PLR) parameters can be used as quantitative biomarkers of neurological function. Since digital infrared pupillometry is expensive, we sought to examine alterations in PLR parameters using a smartphone quantitative pupillometry platform in subjects with acute ischemic stroke (AIS). Materials and methodsPatients were enrolled if they presented to the emergency department as a stroke code activation and had evidence of a large vessel occlusion (LVO) on computed tomography angiography. Controls were enrolled from hospital staff. A smartphone pupillometer was used in AIS patients with LVO pre-mechanical thrombectomy, immediately post-thrombectomy, and at 24 h post-thrombectomy. Clinical and demographic data were collected, along with the proprietary Neurological Pupil index (NPi) score from the NPi-200 digital infrared pupillometer. PLR parameters were compared using mean differences. The absolute and non-absolute inter-eye difference in each parameter for each subject were also analyzed by measuring 1 - (R:L) to determine alteration in the equilibrium between subject pupils. The NPi was analyzed for mean differences between cohorts. ResultsHealthy controls (n = 132) and AIS patients (n = 31) were enrolled. Significant differences were observed in PLR parameters for healthy subjects when compared to pre-thrombectomy subjects in both mean and absolute inter-eye differences after post hoc Bonferroni correction. The proprietary NPi score was not significantly different for all groups and comparisons. ConclusionsSignificant alterations in the PLR were observed in AIS patients with LVO before thrombectomy, indicating the potential use of smartphone pupillometry for detection of LVO.

Quantitative pupillometry for neuroprognostication in comatose post-cardiac arrest patients: A protocol for a predefined sub-study of the Blood pressure and Oxygenations Targets after Out-of-Hospital Cardiac Arrest (BOX)-trial

BackgroundResuscitation guidelines propose a multimodal prognostication strategy algorithm at ≥72 hours after the return of spontaneous circulation to evaluate neurological outcome for unconscious cardiac arrest survivors. Even though guidelines suggest quantitative pupillometry for assessing pupillary light reflex, threshold values are not yet validated.This study aims to validate pre-specified thresholds of quantitative pupillometry by quantitatively assessing the percentage reduction of pupillary size (qPLR) <4% and Neurological Pupil index (NPi) ≤2 and in predicting unfavorable neurological outcome. Both as an isolated predictor and combined with guideline-suggested neuron-specific enolase (NSE) threshold >60 μg L−1 in the current prognostication strategy algorithm. MethodsWe conduct this pre-planned diagnostic sub-study in the randomized, controlled, multicenter clinical trial “Blood Pressure and Oxygenation Targets after Out-of-Hospital Cardiac Arrest-trial”. Blinded to treating physicians and outcome assessors, measurements of qPLR and NPi are obtained from cardiac arrest survivors at time points (±6 hours) of admission, after 24, 48, and 72 hours, or until the time of awakening or death. DiscussionThis study will be the largest prospective study investigating the predictive performance of automated quantitative pupillometry in unconscious patients resuscitated from cardiac arrest. We will test specific threshold values of NPi ≤2 and qPLR <4% to predict unfavorable outcome following cardiac arrest. The validation of pupillometry alone and combined with NSE with the criteria of the current prognostication strategy algorithm will hopefully increase the level of evidence and support clinical neuroprognostication with automated quantitative pupillometry in unconscious post-cardiac arrest patients. Trial registrationRegistered March 30, 2017, at ClinicalTrials.gov (Identifier: NCT03141099).

The Neurological Pupil index for outcome prognostication in people with acute brain injury (ORANGE): a prospective, observational, multicentre cohort study

Improving the prognostication of acute brain injury is a key element of critical care. Standard assessment includes pupillary light reactivity testing with a hand-held light source, but findings are interpreted subjectively; automated pupillometry might be more precise and reproducible. We aimed to assess the association of the Neurological Pupil index (NPi)-a quantitative measure of pupillary reactivity computed by automated pupillometry-with outcomes of patients with severe non-anoxic acute brain injury. ORANGE is a multicentre, prospective, observational cohort study at 13 hospitals in eight countries in Europe and North America. Patients admitted to the intensive care unit after traumatic brain injury, aneurysmal subarachnoid haemorrhage, or intracerebral haemorrhage were eligible for the study. Patients underwent automated infrared pupillometry assessment every 4 h during the first 7 days after admission to compute NPi, with values ranging from 0 to 5 (with abnormal NPi being <3). The co-primary outcomes of the study were neurological outcome (assessed with the extended Glasgow Outcome Scale [GOSE]) and mortality at 6 months. We used logistic regression to model the association between NPi and poor neurological outcome (GOSE ≤4) at 6 months and Cox regression to model the relation of NPi with 6-month mortality. This study is registered with ClinicalTrials.gov, NCT04490005. Between Nov 1, 2020, and May 3, 2022, 514 patients (224 with traumatic brain injury, 139 with aneurysmal subarachnoid haemorrhage, and 151 with intracerebral haemorrhage) were enrolled. The median age of patients was 61 years (IQR 46-71), and the median Glasgow Coma Scale score on admission was 8 (5-11). 40 071 NPi measurements were taken (median 40 per patient [20-50]). The 6-month outcome was assessed in 497 (97%) patients, of whom 160 (32%) patients died, and 241 (47%) patients had at least one recording of abnormal NPi, which was associated with poor neurological outcome (for each 10% increase in the frequency of abnormal NPi, adjusted odds ratio 1·42 [95% CI 1·27-1·64]; p<0·0001) and in-hospital mortality (adjusted hazard ratio 5·58 [95% CI 3·92-7·95]; p<0·0001). NPi has clinically and statistically significant prognostic value for neurological outcome and mortality after acute brain injury. Simple, automatic, repeat automated pupillometry assessment could improve the continuous monitoring of disease progression and the dynamics of outcome prediction at the bedside. NeurOptics.

Intraoperative neurological pupil index and postoperative delirium and neurologic adverse events after cardiac surgery: an observational study

Neurological pupil index (NPi) calculated by automated pupillometry predicts clinical outcomes in critically ill patients. However, there are few data on intraoperative NPi and postoperative outcome after cardiac surgery. We evaluated the relationships between intraoperative NPi and clinical outcomes, such as delirium, in cardiac surgery patients. NPi was measured at baseline, after anesthesia induction, at 30 min intervals after initiation of cardiopulmonary bypass or anastomosis of coronary artery bypass graft, and at skin closure. Abnormal NPi was defined as one or more measurements of NPi < 3.0 during surgery. The worst intraoperative NPi was recorded, then multivariate logistic regression analysis was performed to evaluate the relationship between abnormal NPi and postoperative delirium following cardiac surgery. Among 123 included patients, postoperative delirium developed in 19.5% (24/123) of patients. Intraoperative abnormal NPi was significantly associated with postoperative delirium (odds ratio 6.078; 95% confidence interval 1.845–20.025; P = 0.003) after adjustment for Society of Thoracic Surgeons Predicted Risk of Mortality score, coronary artery disease, and use of calcium channel blockers. In conclusion, abnormal intraoperative NPi independently predicted postoperative delirium following cardiac surgery. Intraoperative application of pupillometry may have prognostic value for development of postoperative delirium, thereby enabling close surveillance and early intervention in high-risk patients.Registry number: ClinicalTrials.gov (NCT04136210).

PupillOmetry for preDIction of DeliriUM in ICU (PODIUM): protocol for a prospective multicentre cohort study

IntroductionDelirium is a severe complication that is associated with short-term adverse events, prolonged hospital stay and neurological sequelae in survivors. Automated pupillometry is an easy-to-use device that allows for accurate...

Neurological Pupil Index and Delayed Cerebral Ischemia after Subarachnoid Hemorrhage: A Retrospective Multicentric Study.

Delayed cerebral ischemia (DCI) occurs in around 30% of patients suffering from nontraumatic subarachnoid hemorrhage (SAH) and is associated with poor neurological outcome. Whether the Neurological Pupil index (NPi) derived from the automated pupillometry could help to diagnose the occurrence of DCI remains unknown. The aim of this study was to investigate the association of NPi with the occurrence of DCI in patients with SAH. This was a multicenter, retrospective cohort study of consecutive patients with SAH admitted to the intensive care units of five hospitals between January 2018 and December 2020 who underwent daily NPi recordings (every 8h) during the first 10days of admission. DCI was diagnosed according to standard definitions (in awake patients) or based on neuroimaging and neuromonitoring (in sedated or unconscious patients). An NPi < 3 was defined as abnormal. The primary outcome of the study was to assess the time course of daily NPi between patients with DCI and patients without DCI. Secondary outcome included the number of patients who had an NPi < 3 before DCI. A total of 210 patients were eligible for the final analysis; DCI occurred in 85 (41%) patients. Patients who developed DCI had similar values of mean and worst daily NPi over time when compared with patients without DCI. Patients with DCI had a higher proportion of at least one NPi < 3 at any moment before DCI when compared with others (39/85, 46% vs. 35/125, 38%, p = 0.009). Similarly, the worst NPi before DCI diagnosis was lower in the DCI group when compared with others (3.1 [2.5-3.8] vs. 3.7 [2.7-4.1], p = 0.05). In the multivariable logistic regression analysis, the presence of NPi < 3 was not independently associated with the development of DCI (odds ratio 1.52 [95% confidence interval 0.80-2.88]). In this study, NPi measured three times a day and derived from the automated pupillometry had a limited value for the diagnosis of DCI in patients with SAH.

Specific thresholds of quantitative pupillometry parameters predict unfavorable outcome in comatose survivors early after cardiac arrest

AimQuantitative pupillometry is the guideline-recommended method for assessing pupillary light reflex for multimodal prognostication in comatose patients resuscitated from out-of-hospital cardiac arrest (OHCA). However, threshold values predicting an unfavorable outcome have been inconsistent across studies; therefore, we aimed to identify specific thresholds for all quantitative pupillometry parameters. MethodsComatose post-OHCA patients were consecutively admitted to the cardiac arrest center at Copenhagen University Hospital Rigshospitalet from April 2015 to June 2017. The parameters of quantitatively assessed pupillary light reflex (qPLR), Neurological Pupil index (NPi), average/max constriction velocity (CV/MCV), dilation velocity (DV), and latency of constriction (Lat) were recorded on the first three days after admission. We evaluated the prognostic performance and identified thresholds achieving zero percent false positive rate (0% PFR) for an unfavorable outcome of 90-day Cerebral Performance Category (CPC) 3–5. Treating physicians were blinded for pupillometry results. ResultsOf the 135 post-OHCA patients, the primary outcome occurred for 53 (39%) patients.On any day during hospitalization, a qPLR < 4%, NPi < 2.45, CV < 0.1 mm/s, and an MCV < 0.335 mm/s predicted 90-day unfavorable neurological outcome with 0% FPR (95%CI: 0–0%), with sensitivities of 28% (17–40%), 9% (2–19%), 13% (6–23%), and 17% (8–26%), respectively on day 1. ConclusionWe found that specific thresholds of all quantitative pupillometry parameters, measured at any time following hospital admission until day 3, predicted a 90-day unfavorable outcome with 0% FPR in comatose patients resuscitated from OHCA. However, at 0% FPR, thresholds resulted in low sensitivity. These findings should be further validated in larger multicenter clinical trials.

Quantitative pupillometry thresholds for early neuroprognostication after cardiac arrest: A BOX-trial substudy

Abstract Funding Acknowledgements Type of funding sources: Private grant(s) and/or Sponsorship. Main funding source(s): Novo Nordisk Foundation Background Quantitative pupillometry as part of multimodal prognostication in comatose out-of-hospital cardiac arrest (OHCA) patients is promising, but the lack of validated thresholds for outcome presents a challenge for clinical use. Studies have suggested that a percentage reduction of pupillary size (qPLR, %) ≤3.8% and a neurological pupil index (NPi, 0-5) ≤2 is 100% specific for poor neurological outcome. However, this remains to be validated in a large consecutive population. Purpose To assess the proposed thresholds for qPLR and NPi for early identification of poor neurological outcome, defined as Cerebral Performance Category (CPC) 3–5 at 3-months follow-up after OHCA. Methods This predefined, prospective substudy from a large multicenter, randomized trial, obtained quantitative pupillometry measurements from consecutively enrolled patients at 0, 24, 48, 72, 96, and 120 hours after OHCA (t0-t120). However, pupillometry was not used to guide clinical decision-making. Specificity and sensitivity were calculated for the proposed thresholds of qPLR and NPi. Overall prognostic performances were assessed with logistic regression and area under the receiver operating characteristic (ROC) curves (AUC). Models were further adjusted for potential confounders. Results Of the 789 patients comprising the BOX-trial population, serial measurements of quantitative pupillometry were performed in a total of 710 (90%) patients. Patients had a mean age of 63±14 (range 18-93) years, predominantly of male sex (82%), with primary outcome occurring in 266 (37%) patients. For all time points, both median values of qPLR and NPi were significantly lower in patients with poor neurological outcome. The highest AUC was found at t48 for both qPLR and NPi. In the unadjusted model, AUC was 0.80 [95%CI 0.76-0.84] for qPLR and 0.79 [95%CI 0.75-0.83] for NPi (Fig 1). In the adjusted model AUC was 0.92 [95%CI: 0.87-0.96] for qPLR and 0.92 [95%CI: 0.88-0.97] for NPi (Fig 2). Both parameters had a significant contribution to the AUC in the adjusted model, with no significant difference in performance between qPLR and NPi in either model. At t48, specificity for CPC 3-5 was 99% [95%CI 97-100] with sensitivity at 20% [95%CI 15-26] for qPLR≤3.8% and 100% [95%CI 99-100] with sensitivity at 10% [95%CI 6-14] for NPi ≤2. At time points t0, t24, t72, t96, and t120 specificity was 91%, 96%, 99%, 100%, and 100%, respectively for qPLR≤3.8%, and 100% for all time points for NPi ≤2. Conclusion The predictive performance of qPLR and NPi was equally good with optimal timing of measurements at 48 hours after admission. The BOX-trial validates thresholds of NPi ≤2 with 100% specificity for outcome at all time points and of qPLR≤3.8% with 99-100% specificity at t48-t120. These findings support the clinical usefulness of quantitative pupillometry for multimodal neuroprognostication of comatose OHCA patients.

Influence of blood-pressure and oxygen levels on the prognostic value of quantitative pupillometry for comatose cardiac arrest patients - a BOX-trial substudy

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.

Quantitative Pupillometry is Not Impacted By IV Opioid or Sedative Bolus Dosing (P11-7.005)

<h3>Objective:</h3> Evaluate effect of intermittent intravenous opioids and sedatives on Neurological Pupil Index (NPi) using Quantitative Pupillometry (QP). <h3>Background:</h3> Opioids and sedatives are widely used in the Neuroscience ICU (NSICU). NPi, an objective measurement of pupillary light reflex (PLR), is a critical component of the neurologic examination and is measured routinely using QP. Yet whether NPi values are affected by opioid or sedative bolus in acutely ill patients is unknown. <h3>Design/Methods:</h3> Prospective, observational, pragmatic study of adult patients (≥18 years old) admitted to the NSICU with any admission diagnosis who received bolus doses of IV opioids or sedatives. 100 patients will be enrolled for final analysis. NPi was assessed using the NPi-300 pupillometer within 30 minutes prior to and 15 minutes after administration of IV opioid or sedative administration. Opioids and sedatives utilized include hydromorphone, fentanyl, morphine, and midazolam. Descriptive data were obtained for demographics. Paired t-test was used to compare pre and post NPi values. <h3>Results:</h3> 39 patients were included in the interim analysis: 54% female, median age 48 (IQR 39–65). Of 39 patients, 35 (90%) received hydromorphone, 2 (5%) received morphine, 1 (2.5%) received fentanyl, and 1 (2.5%) received midazolam. Mean premedication NPi of the RIGHT eye was 4.25 (0.47), and mean premedication NPi of the LEFT eye was 4.27 (0.47). Mean post-medication NPi of the RIGHT eye was 4.26 (0.47), <i>P</i>=0.73. Mean post-medication NPi of the LEFT eye was 4.27 (0.46), <i>P</i>=0.99. Numbers in parenthesis represent standard deviation unless otherwise noted. <h3>Conclusions:</h3> NPi does not significantly differ from before to after administration of bolus IV opioids or sedatives. Significant changes in NPi are unlikely to be related to medication administration and should be correlated clinically. <b>Disclosure:</b> Dr. Battley has nothing to disclose. Ms. Marshall has nothing to disclose. DaiWai Olson has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Minnetronix. The institution of DaiWai Olson has received research support from Neuroptics. The institution of DaiWai Olson has received research support from Ceribell. Sonja Stutzman, 10738 has received publishing royalties from a publication relating to health care. Dr. Reyes has nothing to disclose.