Pupillary Light Reactivity Research Articles

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.

Automated Infrared Pupillometer Use in Assessing the Neurological Status in Pediatric Neurocritical Care Patients: Case Reports and Literature Review

AbstractAutomated infrared pupillometry (AIP) is rapidly becoming an accepted standard for the evaluation of pupil size and reactivity in adult neurocritical care. Recently, pediatric centers are increasingly utilizing this technology, but data supporting its use in children are limited. Our pediatric intensive care unit instituted AIP as a standard of care for pupillary light assessments in neurocritical care patients in early 2020. In this article, we describe four cases highlighting the advantage of using objective assessments of the pupillary light reactivity response measured by the Neurological Pupil index (NPi) to detect early changes in the patient's neurological status. These cases support the applicability of AIP in pediatric neurocritical care as a noninvasive neurologic monitoring tool. The NPi may be superior to manual pupil assessments by providing a numerical scale for accurate trending clinical status of a patient's neurologic condition.

Intérêt de la pupillométrie automatisée dans le pronostic neurologique

La pupillométrie automatisée à infrarouges fait partie des techniques émergentes dans l’arsenal de monitorage neurologique non-invasif. Elle permet une évaluation pupillaire objective et quantitative avant et après stimulation lumineuse. Cette revue détaille la place de la technique en parcourant les résultats les plus récents dans le suivi et l’évaluation pronostique précoce du patient cérébrolésé.

Risk Factors and Prognostic Value of Swirl Sign in Traumatic Acute Epidural Hematoma.

Objective: Acute epidural hematoma (AEDH) is one of the deadliest lesions in patients after traumatic brain injury. AEDH with swirl sign progresses rapidly and requires timely surgical treatment. This study aims to investigate the risk factors for the occurrence of AEDH with swirl sign and its prognostic value.Methods: Retrospective analysis was performed on 131 AEDH patients, who were divided into swirl sign group and non-swirl sign group based on the brain computed tomographic (CT) scan. Patient information, including gender, age, hypertension, mechanism of injury, Glasgow Coma Scale (GCS) score on admission, time from injury to CT scan, pupillary light reactivity on admission, midline shift, location of hematoma, hematoma volume on admission, oral anticoagulation, and Glasgow Outcome Scale (GOS) score at 3 months were collected. Univariate analysis was used to determine the risk factors for the occurrence of swirl sign. The factors with P < 0.05 were recruited into the multivariate logistic regression analysis and predictive receiver operating characteristic (ROC) curve model.Results: Univariate analysis demonstrated that the GCS score on admission (P = 0.007), pupillary light reactivity (P = 0.003), location of hematoma (P < 0.0001), and GOS score at 3 months (P = 0.007) were risk factors for the occurrence of swirl sign. Multivariate logistic regression model revealed that the location of hematoma (OR = 0.121; 95% CI: 0.019–0.786; P = 0.027) was an independent risk factor for swirl sign, and the occurrence of swirl sign was a significant predictor of unfavorable neurological outcomes (OR = 0.100; 95% CI: 0.016–0.630; P = 0.014). ROC curves demonstrated that the GCS score on admission (AUC = 0.655; 95% CI: 0.506–0.804), pupillary light reactivity (AUC = 0.625; 95% CI: 0.474–0.777) and location of hematoma (AUC = 0.788; 95% CI: 0.682–0.893) can predict the occurrence of swirl sign, respectively. Remarkably, the combination of these three factors (AUC = 0.829; 95% CI: 0.753–0.906) provided a greater power to predict the swirl sign.Conclusion: GCS score on admission, pupillary light reactivity, and location of hematoma are risk factors for the occurrence of swirl sign, respectively. The combination of these three factors might be used to predict whether there is swirl sign in AEDH after traumatic brain injury. Furthermore, swirl sign can be used as an effective predictor of poor prognosis in patients.

Pupil Reactivity in Refractory Out-ofHospital Cardiac Arrest Treated by ExtraCorporeal Cardiopulmonary Resuscitation

ObjectiveThe objective of this study was to assess the association of early pupil evaluation with death occurrence on Day 28 in patients with refractory out-of-hospital cardiac arrest (ROHCA) admitted to the intensive care unit (ICU) and treated by extra-corporeal cardiopulmonary resuscitation (eCPR).MethodsThe pupil size (miosis, intermediary or mydriasis) and bilateral pupillary light reactivity (present or absent) were monitored in sedated and paralysed patients treated by eCPR. Mortality was assessed on Day 28.ResultsA total of 46 consecutive patients with ROHCA were included in the study. Thirty (65%) patients died on Day 28. Twenty-seven (90%) patients had pupils non-reactive to light, and 18 (60%) had mydriasis at the ICU admission. Using logistic regression, including age, gender, no flow, low-flow, size and pupil reactivity to light, only the pupillary reactivity to light remained associated with death on Day 28 (Odds ratio=0.12, 95%CI=[0.01–0.96]).ConclusionPupils not reacting to light at the ICU admission were associated with mortality on Day 28 in patients with ROHCA. Pupillary light reactivity is a simple and easy tool that can be used to early detect a poor outcome in patients with ROHCA treated by eCPR.

Neurological Pupil index for Early Prognostication After Venoarterial Extracorporeal Membrane Oxygenation

Venoarterial extracorporeal membrane oxygenation therapy (VA-ECMO) after refractory cardiogenic shock or cardiac arrest has significant morbidity and mortality. Early outcome prediction is crucial in this setting, but data on neuroprognostication are limited. We examined the prognostic value of clinical neurologic examination, using an automated device for the quantitative measurement of pupillary light reactivity. An observational cohort of sedated, mechanically ventilated VA-ECMO patients was analyzed during the early phase after ECMO insertion (first 72 h). Using the NPi-200 automated infrared pupillometer, pupillary light reactivity was assessed repeatedly (every 12 h) by calculating the Neurological Pupil index (NPi). Trends of NPi over time were correlated to 90-day mortality, and the prognostic performance of the NPi, alone and in combination with the 12-h PREDICT VA-ECMO score, was evaluated. One hundred consecutive patients were studied (51 with refractory cardiogenic shock and 49 with refractory cardiac arrest; 12-h PREDICT VA-ECMO, 40%; observed 90-day survival, 43%). Nonsurvivors (n= 57) had significantly lower NPi than did survivors at all time points (all P< .01). Abnormal NPi (< 3, at any time from 24 to 72 h) was 100%specific for 90-day mortality, with 0%false positives. Adding the 12-h PREDICT VA-ECMO score to the NPi provided the best prognostic performance (specificity, 100%[95%CI, 92%-100%]; sensitivity, 60%[95%CI, 46%-72%]; area under the receiver operating characteristic curve, 0.82). Quantitative NPi alone had excellent ability to predict a poor outcome from day 1 after VA-ECMO insertion, with no false positives. Combining NPi and 12-h PREDICT-VA ECMO score increased the sensitivity of outcome prediction, while maintaining 100%specificity.

Feasibility and Variability of Automated Pupillometry Among Stroke Patients and Healthy Participants: Potential Implications for Clinical Practice.

Early neurological deterioration (END) is common after stroke and represents a poor prognostic marker. Manual pupillary assessment to detect END is subjective and has poor interrater reliability. Novel methods of automated pupillometry may be more reliable and accurate. This study aims to evaluate the acceptability and feasibility of automated pupillometry in patients with acute stroke and healthy volunteers and compare its interrater reliability with that of the traditional manual method. Automated and manual pupillary assessments were recorded between 2 independent observers alongside routine neurological observations from 12 acute stroke patients at a high risk of END. The proportion of completed measurements, adverse events, and qualitative feedback from patients and staff nurses was used to assess acceptability and feasibility of automated pupillometry. Paired automated and manual assessments were supplemented with measures from healthy volunteers to analyze measures of variability and agreement. Automated pupillometry was acceptable and safe among 12 acute stroke patients, but feasibility criteria were not attained. Interrater agreement for automated pupillometry was superior to manual assessment for measurements of pupil size, anisocoria, and pupillary light reactivity, for both patients and healthy volunteers. Substantial disparity existed in agreement between automated and manual assessments of these parameters. Automated pupillometry represents an alternative to manual pupillary assessment that may have greater interrater agreement and reliability. As an optimized method of neurological assessment, it has the potential to improve detection and treatment of conditions leading to END after stroke.

Prognostic performance of early absence of pupillary light reaction after recovery of out of hospital cardiac arrest

IntroductionLoss of pupillary light reactivity (PLR) three days after a cardiorespiratory arrest is a prognostic factor. Its predictive value upon hospital admission remains unclear. Our objective was to determine the prognostic value of the absence of PLR upon hospital admission in patients with out-of-hospital cardiac arrest. MethodsWe prospectively included all out-of-hospital cardiac arrests occurring between July 2011 and July 2017 treated by a mobile medical team (MMT) based on data from a French cardiac arrest registry database. PLR was evaluated upon hospital admission and the outcome on day 30. The prognosis was classified as good for Cerebral Performance Category (CPC) 1 or 2, and poor for CPC 3–5 or in case of death. ResultsData from 10151 patients was analysed. The sensitivity and specificity of the absence of PLR for a poor outcome were 72.2% (71.2–73.2) and 68.8% (66.7–70.1), respectively. We identified several variables modifying the sensitivity values and the false positive fraction of a factor, ranging from 0.49 (0.35–0.69) for the Glasgow Coma Scale to 2.17 (1.09–2.48) for pupillary asymmetry. Among those living with CPC 1 or 2 on day 30 (n = 1990; 19.6%), 621 (31.2% (29.2–33.3)) had no PLR upon hospital admission. In the multivariate analysis, loss of PLR was associated with a poor outcome (OR = 3.1 (2.7–3.5)). ConclusionsLoss of pupillary light reactivity upon hospital admission is predictive of a poor outcome after out-of-hospital cardiac arrest. However, it does not have sufficient accuracy to determine prognosis and decision making.

Early Absent Pupillary Light Reflexes After Cardiac Arrest in Patients Treated with Therapeutic Hypothermia.

Loss of pupillary light reactivity is one recognized indicator of poor prognosis after cardiopulmonary resuscitation (CPR). However, drug overdose, low cardiac output, and/or resuscitation drugs can lead to impaired pupillary light reflex. To investigate pupillary light reflex status before therapeutic hypothermia (TH) in relation to neurological outcome, we retrospectively reviewed the data of a prospectively implemented TH protocol in patients with cardiac arrest (CA) at Mayo Clinic in Jacksonville, Florida (January 2006-January 2012), and Mayo Clinic in Scottsdale, Arizona (August 2010-March 2014). During this period, all CA patients who underwent hypothermia were included. These patients were selected from an institutional database and hypothermia data set. The Cerebral Performance Category (CPC) at time of discharge was our primary outcome measure. A CPC of 1 to 2 was defined as good outcome and a CPC from 3 to 5 was defined as poor outcome. We identified 99 patients who had CA treated with TH. Twenty-nine patients (29%) had pupils that were nonreactive to light on admission examination before TH, eight of whom later had return of pupil reactivity by day 3. Two of these 29 patients (6.9%) had good outcome, compared to 24 of 70 patients (34.3%) with pupils that were reactive to light (p = 0.005). Both of these patients had CA after illicit drug overdose. Early nonreactive pupils occurred in almost a third of patients after CPR and before TH in our patient population. Recovery of pupillary light reactivity is possible, and in a small minority of those cases (particularly when CA is preceded by the use of illicit drugs), a good outcome can be achieved.

Automated quantitative pupillometry for the prognostication of coma after cardiac arrest.

Sedation and therapeutic hypothermia (TH) delay neurological responses and might reduce the accuracy of clinical examination to predict outcome after cardiac arrest (CA). We examined the accuracy of quantitative pupillary light reactivity (PLR), using an automated infrared pupillometry, to predict outcome of post-CA coma in comparison to standard PLR, EEG, and somato-sensory evoked potentials (SSEP). We prospectively studied over a 1-year period (June 2012-June 2013) 50 consecutive comatose CA patients treated with TH (33 °C, 24 h). Quantitative PLR (expressed as the % of pupillary response to a calibrated light stimulus) and standard PLR were measured at day 1 (TH and sedation; on average 16 h after CA) and day 2 (normothermia, off sedation: on average 46 h after CA). Neurological outcome was assessed at 90 days with Cerebral Performance Categories (CPC), dichotomized as good (CPC 1-2) versus poor (CPC 3-5). Predictive performance was analyzed using area under the ROC curves (AUC). Patients with good outcome [n = 23 (46 %)] had higher quantitative PLR than those with poor outcome [n = 27; 16 (range 9-23) vs. 10 (1-30) % at day 1, and 20 (13-39) vs. 11 (1-55) % at day 2, both p < 0.001]. Best cut-off for outcome prediction of quantitative PLR was <13 %. The AUC to predict poor outcome was higher for quantitative than for standard PLR at both time points (day 1, 0.79 vs. 0.56, p = 0.005; day 2, 0.81 vs. 0.64, p = 0.006). Prognostic accuracy of quantitative PLR was comparable to that of EEG and SSEP (0.81 vs. 0.80 and 0.73, respectively, both p > 0.20). Quantitative PLR is more accurate than standard PLR in predicting outcome of post-anoxic coma, irrespective of temperature and sedation, and has comparable prognostic accuracy than EEG and SSEP.

Early Prognosis After Severe Traumatic Brain Injury With Minor or Absent Computed Tomography Scan Lesions

To assess the prognostic value of corpus callosum lesions (CCL) and brain stem lesions (BSL) in diffuse axonal injury (DAI) patients. From December 1989 to December 2008, 102 consecutive patients with pure DAI were admitted to our neurosurgical intensive care unit. Age, gender, Acute Physiology and Chronic Health Evaluation score, Glasgow Coma Score (GCS), pupillary light reactivity on admission, brain magnetic resonance imaging (MRI) 24 hours to 72 hours after trauma and sepsis, shock, adult respiratory distress syndrome, renal failure, neurosurgery, high intracranial pressure during the 6 months posttrauma were studied with multiple logistic regression, and Cox's proportional hazards, respectively, considering the Glasgow Outcome Scale and the time to recovery of consciousness as outcome variables. Four variables predicted unfavorable Glasgow Outcome Scale (likelihood ratio p<0.0001; Area Under the Receiver Operator Curve (AUROC)=0.92; Naglekerke's R=0.64; Goodness-of-Fit p=0.8679): age (5-year odds ratio [OR], 1.44; 95% CI, 1.14-1.82; p=0.002), bilateral absence of light reflexes (OR, 11.11; 95% CI, 2.19-57.67; p=0.004), multiplicity of CCL (OR, 29.23; 95% CI, 7.06-121.01; p<0.001), and multiplicity of BSL (OR, 9.43; 95% CI, 2.44-36.42; p=0.001). Four variables affected time to recovery of consciousness: age (hazard ratio, 0.98; 95% CI, 0.97-0.99; p=0.009), bilateral absence of light reflexes (hazard ratio, 0.51; 95% CI, 0.27-0.97; p=0.041), multiplicity of CCL (hazard ratio, 0.40; 95% CI, 0.25-0.66; p<0.001), and total GCS on admission (hazard ratio, 1.45; 95% CI, 1.23-1.71; p<0.001). In DAI patients, bad outcome is predicted by age, bilateral absence of pupillary light reflexes, multiplicity of CCL, and BSL on MRI. Time to recovery of consciousness is predicted by age, bilateral absence of light reflexes, multiplicity of CCL on MRI, and GCS on admission.

Pupillary reactivity as an early indicator of increased intracranial pressure: The introduction of the neurological pupil index

BackgroundThis paper introduces the 7/5/2011al Pupil index (NPi), a sensitive measure of pupil reactivity and an early indicator of increasing intracranial pressure (ICP). This may occur in patients with severe traumatic brain injury (TBI), aneurysmal subarachnoid hemorrhage, or intracerebral hemorrhage (ICH).Methods134 patients (mean age 46 years, range 18–87 years, 54 women and 80 men) in the intensive care units at eight different clinical sites were enrolled in the study. Pupillary examination was performed using a portable hand-held pupillometer.ResultsPatients with abnormal pupillary light reactivity had an average peak ICP of 30.5 mmHg versus 19.6 mmHg for the normal pupil reactivity population (P = 0.0014). Patients with “nonreactive pupils” had the highest peaks of ICP (mean = 33.8 mmHg, P = 0.0046). In the group of patients with abnormal pupillary reactivity, we found that the first evidence of pupil abnormality occurred, on average, 15.9 hours prior to the time of the peak of ICP.ConclusionsAutomated pupillary assessment was used in patients with possible increased ICP. Using NPi, we were able to identify a trend of inverse relationship between decreasing pupil reactivity and increasing ICP. Quantitative measurement and classification of pupillary reactivity using NPi may be a useful tool in the early management of patients with causes of increased ICP.

Early prediction of outcome in very severe closed head injury

People with severe head injury and admission Glasgow Coma Scale (GCS) score < or =5 have a poor outcome and greatly strain limited resources. To identify patients with the best chances of survival, using routine clinical measures. People attending the trauma intensive care unit, who had isolated blunt head injury and GCS< or =5 and who had survived > or =4h, were included in the study, resuscitated and clinically assessed. The GCS score was followed serially after admission. Bivariate analysis of various parameters with outcome was performed using the chi-square test. Serial GCS scores were compared with admission GCS by paired t-testing. Of the 102 patients who were studied prospectively, 78 (76.5%) died and 24 (23.5%) survived. Age, gender, pre-hospital delay and admission GCS scores were comparable between the two groups. Adequate spontaneous respiration, brisk pupillary light reactivity on admission and increase in GCS by at least 2 at 24h after admission significantly affected the outcome (p<0.05). In the presence of all these factors, the survival rate increased from 6.1% to 57.1% (p<0.001). People with GCS score < or =5 still have a reasonable chance of survival, so all patients should be aggressively managed initially. Better survival was observed among those with adequate spontaneous respiration, good pupillary reaction and improvement in GCS of at least 2 at 24h. These clinical parameters can help to predict survival and thus make best use of limited resources.

The effects of mannitol on cerebral edema after large hemispheric cerebral infarct.

To evaluate the effect of a single large dose of mannitol on midline tissue shifts after a large cerebral infarction. Theoretically, mannitol use in the largest cerebral infarctions may preferentially shrink noninfarcted cerebral tissue, thereby aggravating midline tissue shifts and worsening neurologic status. To test this theory, we studied patients with hemispheric infarctions using continuous and sequential MRI during administration of a single dose of mannitol. Patients with neurologic deterioration from complete middle cerebral artery (MCA) infarctions and CT evidence of at least 3 mm of midline shift were studied using T1-weighted three-dimensional multiplanar rapid acquisition gradient echo image data sets acquired at 5- to 10-minute intervals before, during, and after a 1.5 gm/kg bolus infusion of mannitol. Horizontal and vertical displacements were calculated by previously described methods. Glasgow Coma Scale (GCS) and MCA Stroke Scale (MCASS) were measured before and after mannitol administration. Mean changes in tissue shifts were compared using repeated measures analysis of variance. Clinical variables were compared using paired t-tests. Seven patients were enrolled. The final average change in midline shift compared with the initial displacement was 0.0 +/- 1 mm for horizontal (F = 0.06, p = 0.99) and 0.25 +/- 1.3 mm for vertical displacement (F = 0.06, p = 0.99). Whereas average scores for the group did not change, MCASS improved in two, GCS improved in three, and pupillary light reactivity returned in two patients. No patient worsened. Acute mannitol used in patients with cerebral edema after a large hemispheric infarction does not alter midline tissue shifts or worsen neurologic status.

Systemic Atropine Administration During Cardiac Arrest Does Not Cause Fixed and Dilated Pupils

Objectives: Systemic administration of atropine during CPR may postpone brain death determination because of its reputed ability to produce fixed and dilated pupils. We studied the effect of atropine administered in the usual doses as an adjunct to endotracheal intubation and for cardiac arrest to determine if it would interfere with neurological assessment. Design: Two groups of children were studied. Group 1 consisted of 28 patients who received atropine (0.03 ± 0.003 mg/kg) prior to endotracheal intubation. Group 2 consisted of 21 patients previously without evidence of brainstem disease who suffered a witnessed arrest and had prompt return of spontaneous circulation and received an atropine dose of 0.03 ± 0.01 mg/kg. Results: In group 1, pupillary size averaged 4.02 ± 0.78 mm before and 4.75 mm ± .84 mm after atropine ( P Conclusion: Atropine administration in conventional doses causes slight pupillary dilation but does not abolish pupillary light reactivity.

Systemic atropine administration during cardiac arrest does not cause fixed and dilated pupils

Systemic administration of atropine during CPR may postpone brain death determination because of its reputed ability to produce fixed and dilated pupils. We studied the effect of atropine administered in the usual doses as an adjunct to endotracheal intubation and for cardiac arrest to determine if it would interfere with neurological assessment. Two groups of children were studied. Group 1 consisted of 28 patients who received atropine (0.03 +/- 0.003 mg/kg) prior to endotracheal intubation. Group 2 consisted of 21 patients previously without evidence of brainstem disease who suffered a witnessed arrest and had prompt return of spontaneous circulation and received an atropine dose of 0.03 +/- 0.01 mg/kg. In group 1, pupillary size averaged 4.02 +/- 0.78 mm before and 4.75 mm +/- .84 mm after atropine (P less than .001). In group 2, the pupillary examination was conducted 30 minutes after return of spontaneous circulation. The pupillary diameter was 4.80 +/- 0.91 mm. All pupils were reactive to light in both groups. Atropine administration in conventional dose causes slight pupillary dilation but does not abolish pupillary light reactivity.