Assessment of sedation by automated pupillometry in critically ill patients: a prospective observational study.

BACKGROUND: Quantitative measurement of pupil change has not been assessed against the Richmond Agitation and Sedation Scale (RASS) and spectral edge frequency (SEF) during sedation. The aim of this study was to evaluate pupillometry against these measures in sedated critically ill adult patients. METHODS: In ventilated and sedated patients, pupillary variables were measured by automated pupillometry at each RASS level from -5 to 0 after discontinuation of hypnotics, while processed electroencephalogram variables were displayed continuously and SEF was recorded at each RASS level. Correlations were made between percentage pupillary light reflex (%PLR) and RASS, and between %PLR and SEF. The ability of %PLR to differentiate light sedation (RASS ≥-2), moderate (RASS =-3), and deep sedation (RASS ≤-4) was assessed by areas under receiver operating characteristic (ROC) curves. RESULTS: A total of 163 paired measurements were recorded in 38 patients. With decreasing sedation depth, median %PLR increased progressively from 20% (interquartile range 17-25%) to 36% (interquartile range 33-40%) (P<0.001). Strong correlations were found between %PLR and RASS (Rho=0.635) and between %PLR and SEF (R=0.641). Area under the curve (AUC) of 0.87 with a %PLR threshold of 28% differentiated moderate/light sedation from deep sedation with sensitivity of 83% and specificity of 83%. An AUC of 0.82 with a threshold of 31% distinguished light sedation from moderate/deep sedation with a sensitivity of 81% and a specificity of 75%. CONCLUSIONS: Quantitative assessment of %PLR correlates with other indicators of sedation depth in critically ill patients.

Nursing insights on the effectiveness of automated pupillometry in two distinct pediatric intensive care units.

PURPOSE: Automated pupillometry (AP) facilitates objective pupillary assessment. In this study, we aimed at assessing nursing perspective about the utility of AP in neurocritically ill children to understand acceptance and usage barriers to guide development of a standardized use protocol. METHODS: We conducted a web-based, cross-sectional, anonymous, Google™ survey of nurses at two independent pediatric ICUs which have been using AP over last four years. The survey included questions related to user-friendliness, barriers, acceptance, frequency of use, and method of documenting AP findings. RESULTS: A total of 31 nurses responded to the survey. A total of 25 nurses (80.6%) used the automated pupillometer and 19 (61.3%) nurses preferred to use the automated pupillometer on critically ill intubated patients. Respondents rated the pupillometer a median [IQR] frequency of use of 7/10 [4-9] and a mean user-friendliness of 8/10 [7-10]. Barriers to pupillometer use included pupillometer unavailability, technical issues, lack of perceived clinical significance, and infection control. CONCLUSION: Nurses have widely adopted the use of automated pupillometer in the PICU especially for critically ill intubated patients and rate it favorably for user-friendliness. Barriers against its use include limited resources, infection concerns, technical issues, and a lack of perceived clinical significance and training. Implementation of standardized PICU protocol for AP usage in critically ill children, may enhance the acceptance, increase usage and aid in objective assessments. PRACTICE IMPLICATIONS: These findings can be used to create a standardized protocol on implementing automated pupillometry in the PICU for critically ill children.

Nociception assessment with videopupillometry in deeply sedated intensive care patients: Discriminative and criterion validations.

BACKGROUND: Nociceptive assessment in deeply sedated patients is challenging. Validated instruments are lacking for this unresponsive population. Videopupillometry is a promising tool but has not been established in intensive care settings. AIM/OBJECTIVE: To test the discriminate validity of pupillary dilation reflex (PDR) between non-noxious and noxious procedures for assessing nociception in non-neurological intensive care unit (ICU) patients and to test the criterion validity of pupil dilation using recommended PDR cut-off points to determine nociception. METHODS: A single-centre prospective observational study was conducted in medical-surgical ICU patients. Two independent investigators performed videopupillometer measurements during a non-noxious and a noxious procedure, once a day (up to 7 days), when the patient remained deeply sedated (Richmond Agitation-Sedation Scale score: -5 or -4). The non-noxious procedures consisted of a gentle touch on each shoulder and the noxious procedures were endotracheal suctioning or turning onto the side. Bivariable and multivariable general linear mixed models were used to account for multiple measurements in same patients. Sensitivity and specificity, and areas under the curve of the receiver operating characteristic curve were calculated. RESULTS: Sixty patients were included, and 305 sets of 3 measurements (before, during, and after), were performed. PDR was higher during noxious procedures than before (mean difference between noxious and non-noxious procedures = 31.66%). After testing all variables of patient and stimulation characteristics in bivariable models, age and noxious procedures were kept in the multivariable model. Adjusting for age, noxious procedures (coefficient = -15.14 (95% confidence interval = -20.17 to -15.52, p < 0.001) remained the only predictive factor for higher pupil change. Testing recommended cut-offs, a PDR of >12% showed a sensitivity of 65%, and a specificity of 94% for nociception prediction, with an area under the receiver operating curve of 0.828 (95% confidence interval = 0.779-0.877). CONCLUSIONS: In conclusion, PDR is a potentially appropriate measure to assess nociception in deeply sedated ICU patients, and we suggest considering its utility in daily practices. REGISTRATION: This study was not preregistered in a clinical registry. TWEETABLE ABSTRACT: Pupillometry may help clinicians to assess nociception in deeply sedated ICU patients.

Brimonidine eye drops reveal diminished sympathetic pupillary tone in comatose patients with brain injury.

BACKGROUND: There is an urgent need for easy-to-perform bedside measures to detect residual consciousness in clinically unresponsive patients with acute brain injury. Interestingly, the sympathetic control of pupil size is thought to be lost in states of unconsciousness. We therefore hypothesized that administration of brimonidine (an alpha-2-adrenergic agonist) eye drops into one eye should produce a pharmacologic Horner's syndrome if the clinically unresponsive patient is conscious, but not if the patient is unconscious. Here, in a first step to explore this hypothesis, we investigated the potential of brimonidine eye drops to distinguish preserved sympathetic pupillary function in awake volunteers from impairment of sympathetic tone in patients in a coma. METHODS: We enrolled comatose patients admitted for acute brain injury to one of the intensive care units (ICU) of a tertiary referral center, in whom EEG and/or neuroimaging for all practical purposes had ruled out residual consciousness. Exclusion criteria were deep sedation, medications with known drug interactions with brimonidine, and a history of eye disease. Age- and sex-matched healthy and awake volunteers served as controls. We measured pupils of both eyes, under scotopic conditions, at baseline and five times 5-120 min after administering brimonidine into the right eye, using automated pupillometry. Primary outcomes were miosis and anisocoria at the individual and group levels. RESULTS: We included 15 comatose ICU patients (seven women, mean age 59 ± 13.8 years) and 15 controls (seven women, mean age 55 ± 16.3 years). At 30 min, miosis and anisocoria were seen in all 15 controls (mean difference between the brimonidine-treated pupil and the control pupil: - 1.31 mm, 95% CI [- 1.51; - 1.11], p < 0.001), but in none (p < 0.001) of the 15 ICU patients (mean difference: 0.09 mm, 95% CI [- 0.12;0.30], p > 0.99). This effect was unchanged after 120 min and remained robust in sensitivity analyses correcting for baseline pupil size, age, and room illuminance. CONCLUSION: In this proof-of-principle study, brimonidine eye drops produced anisocoria in awake volunteers but not in comatose patients with brain injury. This suggests that automated pupillometry after administration of brimonidine can distinguish between the extremes of the spectrum of consciousness (i.e., fully conscious vs. deeply comatose). A larger study testing the "intermediate zone" of disorders of consciousness in the ICU seems warranted.

Evaluation of static and dynamic Pupillometry changes in men using Silodosin for benign prostatic hypertrophy.

BACKGROUND: Intraoperative floppy iris syndrome is a variant of the small pupil syndrome that has been observed during cataract surgery in some patients currently or previously treated with α1 adrenergic blockers. It is important for cataract surgeons to predict the probable complications preoperatively. Our study aims to evaluate the static and dynamic pupil characteristics of patients treated with silodosin-a selective α1 adrenergic blocker-for benign prostate hypertrophy (BPH) and to compare these values with healthy subjects using an automatic quantitative pupillometry system. METHODS: A total of 74 BPH patients treated with silodosin for six months (group 1) and 30 healthy subjects (group 2) were enrolled in this prospective multidisciplinary cross-sectional study. Static and dynamic pupillometric measurements were obtained under optimized conditions, and the results were compared between the two groups. RESULTS: Seventy-four male patients with a mean age of 63,35 ± 7,21 (46-77) years with BPH treated with silodosin and 30 normal male subjects with a mean age of 63,07 ± 4,73 (52-71) years were analyzed. There were statistically significant differences between the groups with regard to scotopic pupil diameter (PD), high photopic PD, and low photopic PD (p < 0.001, for each one). The patient group had statistically significant higher values of amplitude and velocity of pupil contraction and lower values of duration of pupil contraction and latency as well as duration and velocity of pupil dilation. CONCLUSION: The static and dynamic pupil characteristics of subjects treated with silodosin for BPH are different from those of healthy eyes. In addition, our results may have shed light on the risk for intraoperative floppy iris syndrome (IFIS) before cataract surgery; thus, surgeons can be alert and take precautions.

Automated pupillometry and the FOUR score - what is the diagnostic benefit in neurointensive care?

INTRODUCTION: The Glasgow Coma Scale (GCS) and visual inspection of pupillary function are routine measures to monitor patients with impaired consciousness and predict their outcome in the neurointensive care unit (neuro-ICU). Our aim was to compare more recent measures, i.e. FOUR score and automated pupillometry, to standard monitoring with the GCS and visual inspection of pupils. METHODS: Supervised trained nursing staff examined a consecutive sample of patients admitted to the neuro-ICU of a tertiary referral centre using GCS and FOUR score and assessing pupillary function first by visual inspection and then by automated pupillometry. Clinical outcome was evaluated 6 months after admission using the Glasgow Outcome Scale-Extended. RESULTS: Fifty-six consecutive patients (median age 63 years) were assessed a total of 234 times. Of the 36 patients with at least one GCS score of 3, 13 had a favourable outcome. All seven patients with at least one FOUR score of ≤ 3 had an unfavourable outcome, which was best predicted by a low "brainstem" sub-score. Compared to automated pupillometry, visual assessment underestimated pupillary diameters (median difference, 0.4 mm; P = 0.006). Automated pupillometry detected a preserved pupillary light reflex in 10 patients, in whom visual inspection had missed pupillary constriction. DISCUSSION: Training of nursing staff to implement frequent monitoring of patients in the neuro-ICU with FOUR score and automated pupillometry is feasible. Both measures provide additional clinical information compared to the GCS and visual assessment of pupillary function, most importantly a more granular classification of patients with low levels of consciousness by the FOUR score.

Prediction for the prognosis of diffuse axonal injury using automated pupillometry.

OBJECTIVE: Previous studies have reported various predictive indicators of diffuse axonal injury (DAI), but no consensus has not been reached. Although the efficiency of automated pupillometry in patients with consciousness disorder has been widely reported, there are few reports of its use in patients with DAI. This study aimed to investigate the significance of pupillary findings in predicting the prognosis of DAI. PATIENTS AND METHODS: We included patients admitted to our center with a diagnosis of DAI from June 1, 2021 to June 30, 2022. Pupillary findings in both eyes were quantitatively measured by automated pupillometry every 2 hours after admission. We statistically examined the correlations between automated pupillometry parameters, the patients' characteristics, and outcomes such as the Glasgow Outcome Scale Extended (GOSE) after 6 months from injury, the time to follow command, and so on. RESULTS: Among 22 patients included in this study, five had oculomotor nerve palsy. Oculomotor nerve palsy was correlated with all outcomes, whereas Marshall computed tomography (CT) classification, Injury severity score (ISS) and DAI grade were correlated with few outcomes. Some of the automated pupillometry parameters were significantly correlated with GOSE at 6 months after injury, and many during the first 24 hours of measurement were correlated with the time to follow command. Most of these results were not affected by adjustment using sedation period, ISS or Marshall CT classification. A subgroup analysis of patients without oculomotor nerve palsy revealed that many of the automated pupillometry parameters during the first 24 hours of measurement were significantly correlated with most of the outcomes. The cutoff values that differentiated a good prognosis (GOSE 5-8) from a poor prognosis (GOSE 1-4) were constriction velocity (CV) 1.43 (AUC = 0.81(0.62-1), p = 0.037) and maximum constriction velocity (MCV) 2.345 (AUC = 0.78 (0.58-0.98), p = 0.04). The cutoff values that differentiated the time to follow command into within 7 days and over 8 days were percentage of constriction 8 (AUC = 0.89 (0.68-1), p = 0.011), CV 0.63 (AUC = 0.92 (0.78-1), p = 0.013), MCV 0.855 (AUC = 0.9 (0.74-1), p = 0.017) and average dilation velocity 0.175 (AUC = 0.95 (0.86-1), p = 0.018). CONCLUSIONS: The present results indicate that pupillary findings in DAI are a strong predictive indicator of the prognosis, and that quantitative measurement of them using automated pupillometry could facilitate enhanced prediction for the prognosis of DAI.

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

BACKGROUND: 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. METHODS: 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 ß coefficient. Finally, we developed a web app capable of displaying the probability of stroke diagnosis based on the predictive algorithm. RESULTS: 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. CONCLUSIONS: 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.

The Role of Automated Infrared Pupillometry in Traumatic Brain Injury: A Narrative Review.

Pupillometry, an integral component of neurological examination, serves to evaluate both pupil size and reactivity. The conventional manual assessment exhibits inherent limitations, thereby necessitating the development of portable automated infrared pupillometers (PAIPs). Leveraging infrared technology, these devices provide an objective assessment, proving valuable in the context of brain injury for the detection of neuro-worsening and the facilitation of patient monitoring. In cases of mild brain trauma particularly, traditional methods face constraints. Conversely, in severe brain trauma scenarios, PAIPs contribute to neuro-prognostication and non-invasive neuromonitoring. Parameters derived from PAIPs exhibit correlations with changes in intracranial pressure. It is important to acknowledge, however, that PAIPs cannot replace invasive intracranial pressure monitoring while their widespread adoption awaits robust support from clinical studies. Ongoing research endeavors delve into the role of PAIPs in managing critical neuro-worsening in brain trauma patients, underscoring the non-invasive monitoring advantages while emphasizing the imperative for further clinical validation. Future advancements in this domain encompass sophisticated pupillary assessment tools and the integration of smartphone applications, emblematic of a continually evolving landscape.

The long-term effects of topical latanoprost 0.005% treatment on pupillary functions: A 2-year longitudinal study.

PURPOSE: To investigate the long-term effects of topical latanoprost 0.005% treatment on pupillary functions in early-stage primary open-angle glaucoma (POAG) eyes using automated pupillometry. METHODS: This prospective study involved 20 eyes of 20 treatment-naive subjects with early-stage POAG. After comprehensive ophthalmic examination, static and dynamic pupillometry measurements were performedbefore treatment, at the 1st follow-up visit (1.10 ± 0.30 months) and the 2nd follow-up visit (25.85 ± 10.26 months) after treatment initiation. Dynamic parameters included resting diameter (mm), amplitude (mm), latency (ms), duration (ms), and velocity (mm/s) of pupil contraction and dilation. Static pupillometry parameters were pupil diameter (PD, mm) in high-photopic, low-photopic, mesopic and scotopic conditions. RESULTS: The velocity of pupil dilation significantly decreased during the 1st visit (p = 0.008) and the 2nd visit (p = 0.0003) of treatment compared to the pre-treatment visit. The resting PD was also significantly higher after the 1st visit (p = 0.003) and the 2nd visit (p = 0.001) compared to the pre-treatment visit. However, the difference in resting PD measured between the 1st and 2nd visits did not reach statistical significance (p = 0.065). There were no significant changes in other dynamic parameters (p > 0.05 for all). Additionally, a mild, but not significant, mydriatic effect was observed in PD measurements under scotopic, mesopic and low photopic lighting conditions after follow-up. None of the static and dynamic parameters correlate with age, changes in intraocular pressure (IOP) or mean deviation (MD) values of visual field tests. CONCLUSION: The long-term topical latanoprost 0.005% treatment in early-stage POAG has a slight mydriatic effect on the pupil. Further longitudinal clinical studies with larger patient cohorts are necessary to better understand the effects of latanoprost on pupillary functions.

Automated pupillometry in space neuroscience.

Modern pupillometers are automated, thereby providing an objective, accurate, and reliable evaluation of various aspects of the pupillary light reflex at precision levels that were previously unobtainable. There are many gaps in knowledge regarding pupil size and pupillary light reflex in nervous system changes related to space travel given the previous lack of a precise method to quantitatively measure it. Automated pupillometry has not been used previously in space. This novel tool has promising uses in altered gravity environments as a sensitive non-invasive tool to determine alterations due to headward fluid shifts and elevated intracranial pressure. This article discusses the potential use of automated pupillometry in space for monitoring of astronaut health and neurological pathology.

Neurological Pupillary Index and Disposition at Hospital Discharge following ICU Admission for Acute Brain Injury.

We examined the associations between the Neurological Pupillary Index (NPi) and disposition at hospital discharge in patients admitted to the neurocritical care unit with acute brain injury (ABI) due to acute ischemic stroke (AIS), spontaneous intracerebral hemorrhage (sICH), aneurysmal subarachnoid hemorrhage (SAH), and traumatic brain injury (TBI). The primary outcome was discharge disposition (home/acute rehabilitation vs. death/hospice/skilled nursing facility). Secondary outcomes were tracheostomy tube placement and transition to comfort measures. Among 2258 patients who received serial NPi assessments within the first seven days of ICU admission, 47.7% (n = 1078) demonstrated NPi ≥ 3 on initial and final assessments, 30.1% (n = 680) had initial NPI < 3 that never improved, 19% (n = 430) had initial NPi ≥ 3, which subsequently worsened to <3 and never recovered, and 3.1% (n = 70) had initial NPi < 3, which improved to ≥3. After adjusting for age, sex, admitting diagnosis, admission Glasgow Coma Scale score, craniotomy/craniectomy, and hyperosmolar therapy, NPi values that remained <3 or worsened from ≥3 to <3 were associated with poor outcomes (adjusted odds ratio, aOR 2.58, 95% CI [2.03; 3.28]), placement of a tracheostomy tube (aOR 1.58, 95% CI [1.13; 2.22]), and transition to comfort measures only (aOR 2.12, 95% CI [1.67; 2.70]). Our study suggests that serial NPi assessments during the first seven days of ICU admission may be helpful in predicting outcomes and guiding clinical decision-making in patients with ABI. Further studies are needed to evaluate the potential benefit of interventions to improve NPi trends in this population.

Pupillometry in the follow-up of patients undergoing EVT - prediction of space-occupying hemispheric infarction.

BACKGROUND: Despite benefits of endovascular treatment (EVT) for large vessel occlusion (LVO) ischemic stroke, space-occupying brain edema (BE) represents a detrimental complication. In critical-care settings, CT-imaging is needed for monitoring these patients. Yet, bed-side techniques with the potential to predict whether patients develop BE or not would facilitate a time- and cost-efficient patient care. We assessed clinical significance of automated pupillometry in the follow-up of patients undergoing EVT. METHODS: From 10/2018 to 10/2021, neurocritical-care-unit patients were retrospectively enrolled after EVT of anterior circulation LVO. We monitored parameters of pupillary reactivity [light-reflex-latency (Lat), constriction- and redilation-velocities (CV, DV), percentage-change-of-apertures (per-change); NeurOptics-pupilometer®] up to every hour on day 1-3 of ICU stay. BE was defined as midline shift ≥ 5 mm on follow-up imaging 3-5 days after EVT. We calculated mean values of intra-individual differences between successive pairs of parameters (mean-deltas), determined best discriminative cut-off values for BE development (ROC-analyses), and evaluated prognostic performance of pupillometry for BE development (sensitivity/specificity/positive-/negative-predictive-values). RESULTS: 3241 pupillary assessments of 122 patients [67 women, 73 years (61.0-85.0)] were included. 13/122 patients developed BE. Patients with BE had significantly lower CVs, DVs, and smaller per-changes than patients without BE. On day 1 after EVT mean-deltas of CV, DV, and per-changes were significantly lower in patients with than without BE. Positive-predictive-values of calculated thresholds to discriminate both groups were considerably low, yet, we found high negative-predictive-values for CV, DV, per-changes, and mean-deltas (max.: 98.4%). CONCLUSION: Our data suggest associations between noninvasively detected changes in pupillary reactivity and BE early after LVO-EVT. Pupillometry may identify patients who are unlikely to develop BE and may not need repetitive follow-up-imaging or rescue-therapy.

Automated pupillometry and optic nerve sheath diameter ultrasound to define tuberculous meningitis disease severity and prognosis.

BACKGROUND: Tuberculous meningitis (TBM) causes high mortality and morbidity, in part due to raised intracranial pressure (ICP). Automated pupillometry (NPi) and optic nerve sheath diameter (ONSD) are both low-cost, easy-to-use and non-invasive techniques that correlate with ICP and neurological status. However, it is uncertain how to apply these techniques in the management of TBM. METHODS: We conducted a pilot study enrolling 20 adults with TBM in the Hospital for Tropical Diseases, Ho Chi Minh City, Vietnam. Our objective was to investigate the relationships between baseline and serial measurements of NPi and ONSD and disease severity and outcome. Serial NPi and ONSD were performed for 30 days, at discharge, and at 3-months, with measurements correlated with clinical progression and outcomes. RESULTS: ONSD and NPi measurements had an inverse relationship. Higher ONSD and lower NPi values were associated with lower Glasgow coma score. Baseline NPi was a strong predictor 3-month outcome (median NPi 4.55, interquartile range 4.35-4.65 for good outcomes versus 2.60, IQR 0.65-3.95 for poor outcomes, p = 0.002). Pupil inequality (NPi ≥0.7) was also strongly associated with poor 3-month outcomes (p = 0.006). Individual participants' serial NPi and ONSD were variable during initial treatment and correlated with clinical condition and outcome. CONCLUSION: Pupillometry and ONSD may be used to predict clinical deterioration and outcome from TBM. Future, larger studies are need explore the optimal timing of measurements and to define how they might be used to optimise treatments and improve outcomes from TBM.

Neurological pupil index and its association with other prognostic tools after cardiac arrest: A post hoc analysis.

INTRODUCTION: We evaluated the concordance of the Neurological pupil Index (NPi) with other predictors of outcome after cardiac arrest (CA). METHODS: Post hoc analysis of a prospective, international, multicenter study including adult CA patients. Predictors of unfavorable outcome (UO, Cerebral Performance Category of 3-5 at 3 months) included: a) worst NPi ≤ 2; b) presence of discontinuous encephalography (EEG) background; c) bilateral absence of N20 waves on somatosensory evoked potentials (N20ABS); d) peak neuron-specific enolase (NSE) blood levels > 60 mcg/L; e) myoclonus, which were all tested in a subset of patients who underwent complete multimodal assessment (MMM). RESULTS: A total of 269/456 (59 %) patients had UO and 186 (41 %) underwent MMM. The presence of myoclonus was assessed in all patients, EEG in 358 (78 %), N20 in 186 (41 %) and NSE measurement in 228 (50 %). Patients with discontinuous EEG, N20ABS or high NSE had a higher proportion of worst NPi ≤ 2. The accuracy for NPi to predict a discontinuous EEG, N20ABS, high NSE and the presence of myoclonus was moderate. Concordance with NPi ≤ 2 was high for NSE, and moderate for discontinuous EEG and N20ABS. Also, the higher the number of concordant predictors of poor outcome, the lower the observed NPi. CONCLUSIONS: In this study, NPi ≤ 2 had moderate to high concordance with other unfavorable outcome prognosticators of hypoxic-ischemic brain injury. This indicates that NPi measurement could be considered as a valid tool for coma prognostication after cardiac arrest.

Assessment of Combination of Automated Pupillometry and Heart Rate Variability to Detect Driving Fatigue.

Objectives: Approximately 20~30% of all traffic accidents are caused by fatigue driving. However, limited practicability remains a barrier for the real application of available techniques to detect driving fatigue. Use of pupillary light reflex (PLR) may be potentially effective for driving fatigue detection. Methods: A 90 min monotonous simulated driving task was utilized to induce driving fatigue. During the task, PLR measurements were performed at baseline and at an interval of 30 min. Subjective rating scales, heart rate variability (HRV) were monitored simultaneously. Results: Thirty-two healthy volunteers in China participated in our study. Based on the results of subjective evaluation and behavioral performances, driving fatigue was verified to be successfully induced by a simulated driving task. Significant variations of PLR and HRV parameters were observed, which also showed significant relevance with the change in Karolinska Sleepiness Scale at several timepoints (|r| = 0.55 ~ 0.72, P < 0.001). Furthermore, PLR variations had excellent ability to detect driving fatigue with high sensitivity and specificity, of which maximum constriction velocity variations achieved a sensitivity of 85.00% and specificity of 72.34% for driving fatigue detection, vs. 82.50 and 78.72% with a combination of HRV variations, a nonsignificant difference (AUC = 0.835, 0.872, P > 0.05). Conclusions: Pupillary light reflex variation may be a potential indicator in the detection of driving fatigue, achieving a comparative performance compared with the combination with heart rate variability. Further work may be involved in developing a commercialized driving fatigue detection system based on pupillary parameters.

Instrumental Evaluation of COVID-19 Related Dysautonomia in Non-Critically-Ill Patients: An Observational, Cross-Sectional Study.

Coronavirus disease-19 (COVID-19) is a predominantly respiratory syndrome. Growing reports about a SARS-CoV-2 neurological involvement, including autonomic dysfunction (AD), have been reported, mostly in critically-ill patients, or in the long-COVID syndrome. In this observational, cross-sectional study, we investigated the prevalence of AD in 20 non-critically-ill COVID-19 patients (COVID+ group) in the acute phase of the disease through a composite instrumental evaluation consisting of Sudoscan, automated pupillometry, heart rate variability (HRV), and pulse transit time (PTT). All the parameters were compared to a control group of 20 healthy volunteers (COVID- group). COVID+ group presented higher values of pupillary dilatation velocities, and baseline pupil diameter than COVID- subjects. Moreover, COVID+ patients presented a higher incidence of feet sudomotor dysfunction than COVID- group. No significant differences emerged in HRV and PTT parameters between groups. In this study we observed the occurrence of autonomic dysfunction in the early stage of the disease.

Quantification of RAPD by an automated pupillometer in asymmetric glaucoma and its correlation with manual pupillary assessment.

PURPOSE: The relative afferent pupillary defect (RAPD) is an important sign of asymmetrical retinal ganglion cell damage. The purpose of this study was to quantify RAPD by a pupillometer (RAPiDo, Neuroptics) and assess its correlation with asymmetric glaucoma and manual pupillary assessment. METHODS: A total of 173 subjects were enrolled in the study and categorized into glaucoma, n = 130, and control, n = 43. Subjects were all recruited in the Glaucoma Clinic of the Aravind Eye Hospital in Madurai during their follow-up. They were 18 years and older, with best corrected visual acuity of 6/36 or better. Exclusion criteria included all retinal pathologies, optic atrophies, ocular injuries, severe uveitis, cloudy corneas, dense cataracts, or use of mydriatics or miotic drugs. RAPD was assessed in all subjects using an automated pupillometer and the results were compared with the swinging flash light test conducted on the same subjects by an experienced ophthalmologist. We looked at the correlation between RAPD and the intereye difference in cup-to-disc ratio (CDR), mean deviation (MD) of visual field testing, and retinal nerve fiber layer (RNFL) thickness. Sensitivity and specificity were assessed by area under the receiver operator characteristic (AUROC) analysis. RESULTS: Glaucoma patients had significant RAPD (0.55 ± 0.05 log units) when compared with the controls (0.25 ± 0.05 log units), P < 0.001. Significant intereye differences in CDR, MD, and RNFL between glaucoma and control (P < 0.001) were seen. There was a good correlation between the magnitude and sign of RAPD and these intereye differences in CDR (r = 0.52, P < 0.001), MD (r = 0.44, P < 0.001) and RNFL thickness (r = 0.59, P < 0.001). When compared with the experienced ophthalmologist, AUROC was 0.94, with 89% sensitivity and 91.7% specificity. CONCLUSION: The good correlation between the magnitude of RAPD, as measured by the automated pupillometer, and intereye differences in MD, CDR, and RNFL thickness in glaucomatous, and the good sensitivity and specificity when compared with the experienced ophthalmologist, suggest that pupillometry may be useful as a screening tool to assess asymmetric glaucoma.

Automated Pupillometry and Detection of Clinical Transtentorial Brain Herniation: A Case Series.

Introduction: Transtentorial herniation (TTH) is a life-threatening neurologic condition that typically results from expansion of supratentorial mass lesions. A change in bedside pupillary examination is central to the clinical diagnosis of TTH. Materials and. Methods: To quantify the changes in the pupillary examination that precede and accompany TTH and its treatment, we evaluated 12 episodes of herniation in three patients with supratentorial mass lesions using automated pupillometry (NeurOptics, Inc., Irvine, CA). Herniation was defined clinically by the onset of fixed and dilated pupils in association with decreased levels of consciousness. Automated pupillometry was measured simultaneously with the bedside clinical examination, but the clinical team was blinded to these results and could not act on the data. Data from the pupillometer were downloaded 1-2 times per week onto a secured laptop, and data processing was facilitated by the use of Mathematica 8.0. Results: Neurologic Pupil Index measurements, values generated by the pupillometer based on an algorithm that incorporates pupillary size and reactivity in a normal population, were found to be abnormal before 73% of TTHs. This abnormality occurred at a median of 7.4 h before TTH. All episodes of TTH were reversed after clinical intervention at a median of 43 min after the event. The value did not fall to 0 in 42% of clinical herniations, but it did decrease to very abnormal values of 0.5-0.8. Conclusions: The potential of automated pupillometry to guide the management of severely injured neurologic patients is intriguing and warrants further study in the critical care unit and beyond. The utility of a portable device in the combat setting may allow for triage of patients with severe neurologic injury.

Assessment of bilateral pupillary centroid characteristics at varying illuminations and post-photopic flash response using an automated pupillometer.

BACKGROUND: The aim was to assess the symmetry and magnitude of illumination-dependent centroid shift and of post-photic flash re-dilatation response for normal pupils. METHODS: This cross-sectional, observational, inter-eye comparative study was performed at a specialty hospital. Fifty eyes (25 volunteers) without any ocular abnormality underwent pupillometry for scotopic (0.4 lux), mesopic (4.0 lux), photopic conditions (40 lux) and for rate of pupillary re-dilatation after a photopic flash (500 lux) with an inbuilt pupillometer on a Scheimpflug device (Sirius, CSO, Italy). Main outcome measures were pupillary centroids at different illuminations and time-dependent pupil diameters after a photic flash response. RESULTS: The mean pupil size for scotopic, photopic and mesopic pupils were significantly different (p < 0.001, ANOVA) for right and left eyes, analysed separately. The post-photic flash re-dilatation diameter was measured at zero, one, two, four, six, eight and 10 seconds after the flash. The mean diameters at given times post-photic flash were comparable in fellow eyes (p > 0.5, t-test) and highly correlated (r ≥ 0.8, p < 0.05 at all timed comparisons). The mean pupil diameter followed a time-dependent cubic function for both the right and left eyes. Speed was also governed by a time-dependent cubic function for both the right and the left eyes. CONCLUSIONS: Fellow eye symmetry is seen in illumination-governed centroid shifts and the post-flash re-dilatation response. The pupil dilates back briskly with a time-dependent cubic function, which is similar for fellow eyes in normal patients.