Neurological Pupil Index Research Articles

Quantitative Pupillometry in Patients with Surgical Decompression (P11-7.006)

<h3>Objective:</h3> In this study, we aim to describe quantitative pupil reactivity and size characteristics post-surgical decompression. <h3>Background:</h3> Poor pupil reactivity and asymmetry are potential hallmarks of worsening intracranial injury in patients with acute neurological conditions. However, their clinical significance after intracranial surgery, when mass effect is less likely to directly affect midbrain pupillary pathways, is unclear. <h3>Design/Methods:</h3> We performed a retrospective chart review of patients with quantitative pupillometry who received decompressive hemicraniectomy for ischemic stroke, traumatic brain injury (TBI), or intracranial hemorrhage (ICH). We identified clinical and radiological neuroworsening within 1 hour of pupil measurements. We report abnormal pupils, defined as abnormal reactivity (Neurologic Pupil Index (NPi) &lt;3), or asymmetric pupil reactivity (NPi difference ≥ 0.7), or asymmetric size (&gt;1 mm). We also tested abnormal pupil association with clinical and radiographic signs of neuroworsening before and after decompression. <h3>Results:</h3> Of 24 patients, the mean age was 45.29 ± 19.23 years and 16 were male (66.7%). Thirteen patients received hemicraniectomies for stroke (N=7) or ICH (N=6; spontaneous or related to another injury), 9 had hemicraniectomy for acute subdural hemorrhage, and 2 underwent suboccipital craniectomies for posterior circulation ICH. For all patients, pupil abnormalities occurred in 53.82% of post-surgical measurements, as compared to 45.5% of available pre-surgical measurements. Within the subgroup of patients with ≥3 measurements before and after surgery (n=13), the median minimum NPi post-surgery was lower than pre-surgery (3.8 [2.7–3.39] v. 3.9 [2.7–3.51], p &lt; 0.001). Post-surgery, decreased NPi was associated with loss of cranial nerves, motor decline, and refractory intracranial pressure. <h3>Conclusions:</h3> Abnormalities in pupil reactivity and asymmetry occur frequently post-surgical decompression and are affiliated with neuroworsening events. Close quantitative monitoring of pupils may be indicated even after surgical decompression to identify episodes of neuroworsening, but further definitive studies are necessary. <b>Disclosure:</b> Ms. Hupp has nothing to disclose. The institution of Mr. Cronin has received research support from American Heart Association. Mrs. Kim has received personal compensation for serving as an employee of Boston Medical Center. Dr. Ong has nothing to disclose.

Comparison of effects of volatile and intravenous anesthetics on pupillary function during general anesthesia in children: A prospective observational study.

The light reflex, which reflects central nervous system dysfunction, can also be affected by anesthetic agents. We evaluated whether these effects differed according to the anesthetic agent in pediatric patients. Twenty children aged 3-12 years who were scheduled to undergo elective surgery under general anesthesia were randomly allocated to propofol and sevoflurane groups and underwent pupillometric assessments at five points during anesthesia: T1, after confirming loss of consciousness; T2, after endotracheal intubation; T3, at the time of skin incision; T4, 1 h after skin incision; and T5, before endotracheal extubation. The primary outcome was the Neurological Pupil index at T4, and the secondary outcomes were other pupillometric parameters, including pupil diameter, percentage of change in pupil diameter, dilation velocity, and constriction velocity. At T4, the Neurological Pupil index was significantly lower in the sevoflurane group (median difference, 0.30; 95% CI, 0.00 to 0.70; p = .036). Furthermore, the Neurological Pupil index at all time points was lower in the sevoflurane group. The time-and-group interaction effects on constriction velocity and dilation velocity were significantly different [F(1, 4) = 16.68, p = .002; F(1, 4) = 14.78, p = .008, respectively] but were not different on the Neurological Pupil index, pupil diameter, and percentage of change in pupil diameter. No intergroup differences were observed in the baseline characteristics, the flow rate of remifentanil at each time point, and total infused remifentanil. The Neurological Pupil index value in pediatric patients under general anesthesia is affected by the anesthetic agent used; this factor requires consideration in evaluations of the Neurological Pupil index during general anesthesia.

Quantitative Pupillometry Values are Remarkably Similar Before and After Neuroimaging

BackgroundAutomated assessment of the pupillary light reflex (PLR) is becoming more mainstream, yet there is much to learn about the correlations between automated PLR metrics and standard practice. This study explores the feasibility and potential value of assessing PLR using quantitative pupillometry (QP) in patients with critical neurologic illness before and after neuroimaging. MethodsPLR assessments using QP were taken within 30 minutes before and 30 minutes after computerized tomography (CT) or magnetic resonance imaging (MRI) on patients in the neuroscience intensive care unit. ResultsFifty patients were enrolled. The neurological pupil index (NPi®) was 3.98 (1.12) in the right eye and 3.96 (1.0) in the left eye before imaging, and 4.13 (1.08) in the right eye and 4.08 (0.93) in the left eye after imaging. Although the before and after difference in the left eye was a statistically significant (p < .01), these differences were not clinically relevant. Roughly 8% of subjects showed improvement in NPi scores from abnormal (<3.0) before imaging, to normal (>3.0) after. ConclusionObtaining QP readings before and after neuroimaging is feasible and safe. Yet, these data suggest it may not be necessary to obtain pre-QP and post-QP readings when the NPi is normal before CT or MRI.

Quantitative pupillary light reflex assessment for prognosis of carbon monoxide poisoning.

A non-reactive pupil in standard pupillary light reflex (sPLR) is regarded as a factor predicting neurological sequelae at 1-month after carbon monoxide (CO) poisoning. An automated pupillometer is used in the intensive care unit to quantitatively assess PLR. Quantitative PLR (qPLR) was superior to sPLR using penlight for prognosis of various neurological diseases. Therefore, this study aimed to analyze whether quantitative pupillary variables (neurological Pupil index [NPi] and qPLR) are superior to sPLR in predicting 1-month neurocognitive sequelae after acute CO poisoning. We performed a prospective observational study of consecutive patients with acute CO poisoning admitted to an emergency department (ED) between August 2019 and December 2020 in a single academic medical center. sPLR and pupillometer examinations (qPLR and NPi) were performed by emergency physicians at the ED on hospital days 0-2. The lowest values among those recorded within 24 h and during the total measurement period were considered the 24-h and total lowest values, respectively. Global Deterioration Scale scores were measured at 1 month as an outcome and were dichotomized into favorable (1-4) or poor (5-7) outcomes. We analyzed the data of 104 adult patients with acute CO poisoning. qPLR was significantly higher in the favorable outcome group than in the poor outcome group 24-h and total lowest values (21.2% vs. 15.0%, p = 0.006 and 21.0% vs. 14.8%, p = 0.006). qPLR <18% had fair predictive power for poor neurocognitive outcomes [area under the curve (AUC), 0.70; 95% confidence interval (0.60-0.78)]. Among the patients with decreased mental status (Glasgow Coma Scale ≤12), the power of NPi and qPLR increased [AUC, 0.72 and AUC, 0.80]. NPi < 1 and qPLR <18% showed sensitivity (9.5% vs. 76.2%) and specificity (98.8% vs. 67.5%) for the prediction of poor outcomes. qPLR was significantly superior to sPLR in predicting poor neurocognitive outcomes at 1 month after CO poisoning (p = 0.007). qPLR and NPi were superior to sPLR in terms of predicting poor neurocognitive outcomes. qPLR and NPi measured from hospital days 0-2 may be valuable in predicting neurocognitive outcome.

Fixed and dilated pupils by pupillometer in lateralized periodic discharges: a case report in the neurocritical care unit

Background: Fixed and dilated pupils (FDPs) have become synonymous with devastating neurological damage and brainstem injury commonly associated with mass effect and herniation. Infrequently, changes in pupillary light response have been described with seizures; however, the loss of pupillary response with documented Neurological Pupil index has not been well established in patients with seizures.Case Report: We present a case report describing a middle-aged female patient with focal status epilepticus with intermittent FDPs. An abnormal pupillary response occurred with right hemispheric lateralized periodic discharges and resolution with anti-seizure medication escalation. To our knowledge, this is the first description of objective documentation of reversible FDP as a possible clinical correlate of lateralized periodic discharges. Conclusion: The use of handheld automated pupillometry in conjunction with electroencephalogram (EEG) has provided the therapeutic direction. Further research is warranted to fully describe the mechanistic underpinnings of these observations.

Quantitative pupillometry and radiographic markers of intracranial midline shift: A pilot study.

Asymmetric pupil reactivity or size can be early clinical indicators of midbrain compression due to supratentorial ischemic stroke or primary intraparenchymal hemorrhage (IPH). Radiographic midline shift is associated with worse functional outcomes and life-saving interventions. Better understanding of quantitative pupil characteristics would be a non-invasive, safe, and cost-effective way to improve identification of life-threatening mass effect and resource utilization of emergent radiographic imaging. We aimed to better characterize the association between midline shift at various anatomic levels and quantitative pupil characteristics. We conducted a multicenter retrospective study of brain CT images within 75 min of a quantitative pupil observation from patients admitted to Neuro-ICUs between 2016 and 2020 with large (>1/3 of the middle cerebral artery territory) acute supratentorial ischemic stroke or primary IPH > 30 mm3. For each image, we measured midline shift at the septum pellucidum (MLS-SP), pineal gland shift (PGS), the ratio of the ipsilateral to contralateral midbrain width (IMW/CMW), and other exploratory markers of radiographic shift/compression. Pupil reactivity was measured using an automated infrared pupillometer (NeurOptics®, Inc.), specifically the proprietary algorithm for Neurological Pupil Index® (NPi). We used rank-normalization and linear mixed-effects models, stratified by diagnosis and hemorrhagic conversion, to test associations of radiographic markers of shift and asymmetric pupil reactivity (Diff NPi), adjusting for age, lesion volume, Glasgow Coma Scale, and osmotic medications. Of 53 patients with 74 CT images, 26 (49.1%) were female, and median age was 67 years. MLS-SP and PGS were greater in patients with IPH, compared to patients with ischemic stroke (6.2 v. 4.0 mm, 5.6 v. 3.4 mm, respectively). We found no significant associations between pupil reactivity and the radiographic markers of shift when adjusting for confounders. However, we found potentially relevant relationships between MLS-SP and Diff NPi in our IPH cohort (β = 0.11, SE 0.04, P = 0.01), and PGS and Diff NPi in the ischemic stroke cohort (β = 0.16, SE 0.09, P = 0.07). We found the relationship between midline shift and asymmetric pupil reactivity may differ between IPH and ischemic stroke. Our study may serve as necessary preliminary data to guide further prospective investigation into how clinical manifestations of radiographic midline shift differ by diagnosis and proximity to the midbrain.

Early quantitative pupillary response parameters have high predictive value for 30-day mortality in patients resuscitated from out-of-hospital cardiac arrest

Abstract Background Despite adequate post-resuscitation treatment following out-of-hospital cardiac arrest (OHCA), early risk of death remains high due to irreversible anoxic brain injury. Objective Neuroprognostication is pivotal, and automated quantitative pupillometry has become an essential part of early multimodal approach. Several quantitative pupillary response parameters are now available, but little evidence exist on their value and timing in neuroprognostication. Purpose To evaluate prognostic value of standard parameters of quantitative pupillometry in OHCA patients. Methods In this observational study we included 138 comatose patients resuscitated from OHCA admitted to a tertiary cardiac intensive care unit. With quantitative pupillometry, change in pupil size (%CH, %), Neurological Pupil index (NPi, scalar value 0–5), constriction velocity (CV, mm/s), maximum CV (MCV, mm/s), dilation velocity (DV, mm/s) and latency of constriction (Lat, s) were measured at admission, at the 24 hours (24h), and 48-hours (48h) time points. Receiver operating characteristics (ROC) curves with calculation of area under the curve (AUC) were applied for assessment of association with 30-day mortality. Results The population were predominantly males, had a mean age of 61±12 years, and 120 (87%) had shockable primary rhythm, 122 (88%) had witnessed cardiac arrest and 51 (37%) died in the first 30 days. Median %CH, CV, MCV, DV and NPi values were significantly lower for diseased patients compared to survivors. ROC analyses (Figure 1) present all parameters, except NPi, at admission with numerically highest values of AUC at 0.82, 0.76, 0.73, and 0.81 for %CH, CV, MCV, and DV respectively, and for NPi at 48h with AUC at 0.81. The admission time point still presented the highest AUC values, &amp;gt;0.84, for CV, MCV, and DV in an adjusted model. Of all the parameters, %CH and NPi maintained the highest prognostic values through all time points, and %CH performed best at admission with AUC at 0.87 and NPi at 24h with AUC at 0.91. At admission the threshold value with 100% specificity for predicting 30-day mortality were 3.75, 0.09, 0.33, and 0.05, with negative predictive value (NPV [95% confidence interval]) at 71% [67–74], 66% [64–69], 67% [65–70], and 69% [66–72] for %CH, CV, MCV, and DV respectively. NPi had best performance at 24h with a cutoff value of 2.90 and NPV at 64% [63–64]. Conclusion %CH and NPi were the strongest prognostic tools for 30-day mortality. Values below 3.75% for %CH at admission and 2.90 for NPi at 24h after archived 100% specificity for 30-day mortality, with NPV at 71% [67–74] and 64% [63–64] respectively. Although performance was persistently high, %CH, CV, MCV, and DV presented numerically highest AUC at admission. Additional parameters of CV, MCV, and DV were also significantly associated with outcome and future research should focus on validation and possible combining these measures into useful indices. Funding Acknowledgement Type of funding sources: Private company. Main funding source(s): Novo Nordisk Foundation

The Evaluation of Skin Turgor in Relation to Changes in Intracranial Pressure in Patients After Decompressive Hemicraniectomy.

Introduction Decompressive hemicraniectomies have been the mainstay of treating medically refractory elevated intracranial pressures (ICPs). Afterward, ICP continues to be monitored. However, the reliability of monitoring the ICP in a patient after craniectomy has been shown to be variable, at best. We propose the use of a durometer to investigate a temporal relationship between skin turgor and elevated ICP. Methods Patients were included via the following criteria: age >18 and unilateral decompressive craniectomy, with an external ventricular drain (EVD) in place. Patients were excluded if they were younger than 18, underwent bilateral decompressive craniectomy, or did not have an ICP monitor. Skin turgor over the skin flap was measured with a durometer over the center of the defect. ICPs were monitored using an EVD. The optic nerve sheath diameter (ONSD) was measured with ultrasound with the eye closed and Tegaderm (3M, Saint Paul, MN) covering the eyelid. The optic nerve was measured 3 mm behind the globe, and the diameter of the optic nerve at the widest point was recorded. The Neurological Pupil index (NPi) was recorded with a pupillometer. Results Fourteen patients were included, with over 100 data points for ICP, skin turgor, ONSD, and NPi. Five patients went on to have elevated ICP after decompressive hemicraniectomy. The correlation coefficient (R) for ONSD to ICP correlation was 0.62. The R for ICP to skin turgor was 0.31. The data shows that a skin turgor of >9 is related to increasing ICP within 24 hours, a skin turgor of 6-9 is a warning, and a skin turgor of <6 is normal. Conclusion A temporal relationship between skin turgor and ICP exists, which could be used to predict impending elevations in ICP sooner than an ICP monitor can determine. By using this in conjunction with traditional methods of evaluating these patients, we could sooner act on elevations in ICP and potentially improve outcomes.

Evaluating the Reliability of Neurological Pupillary Index as a Prognostic Measurement of Neurological Function in Critical Care Patients.

BackgroundNeurological pupil index (NPi) is a novel method of assessing pupillary size and reactivity using pupillometry to reduce human subjectivity. This paper aims to evaluate the use of NPi as a potential prognostic tool in a broad population of neurocritical care patients by observing the correlation between NPi, modified Rankin Scale (mRS), and Glasgow Coma Scale (GCS).MethodsOur data was collected from 194 patients in the neurosurgical intensive care unit (ICU) at Arrowhead Regional Medical Center (ARMC), as determined by the power calculation. We utilized the Kolmogorov-Smirnova and Shapiro-Wilk normality tests with Lilliefors significance correction. Pearson product-moment correlation was performed between average final NPi and final GCS. Multi-variate linear regression and analysis of variance (ANOVA) were used to evaluate the association and predictive capabilities of NPi on GCS and discharge mRS. Finally, we evaluated whether age, ethnicity, sex, length of stay (LOS), or discharge location were significantly associated with NPi. ResultsWe observed a significant correlation between final GCS and NPi (r=0.609, p<0.001). Our regression analysis revealed that NPi significantly predicted GCS and mRS scores; however, no associations were found between age, ethnicity, sex, LOS, or discharge location. Limitations of our study include a single institutional study with a lack of disease subtyping and the inability to quantify the predictive ability of NPi.ConclusionThe analysis revealed a strong correlation between final GCS and average final NPi. NPi was also able to significantly predict GCS and mRS scores. The correlation between NPi and established methods to determine neurological function, such as mRS and GCS, suggests that NPi can be a good prognostication tool for neurological diseases.

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

IntroductionWe evaluated the concordance of the Neurological pupil Index (NPi) with other predictors of outcome after cardiac arrest (CA). MethodsPost 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). ResultsA 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. ConclusionsIn 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.

A differential of the left eye and right eye neurological pupil index is associated with discharge modified Rankin scores in neurologically injured patients

BackgroundAutomated infrared pupillometry (AIP) and the Neurological Pupil index (NPi) provide an objective means of assessing and trending the pupillary light reflex (PLR) across a broad spectrum of neurological diseases. NPi quantifies the PLR and ranges from 0 to 5; in healthy individuals, the NPi of both eyes is expected to be ≥ 3.0 and symmetric. AIP values demonstrate emerging value as a prognostic tool with predictive properties that could allow practitioners to anticipate neurological deterioration and recovery. The presence of an NPi differential (a difference ≥ 0.7 between the left and right eye) is a potential sign of neurological abnormality.MethodsWe explored NPi differential by considering the modified Rankin Score at discharge (DC mRS) among patients admitted to neuroscience intensive care units (NSICU) of 4 U.S. and 1 Japanese hospitals and for two cohorts of brain injuries: stroke (including subarachnoid hemorrhage, intracerebral hemorrhage, acute ischemic stroke, and aneurysm, 1,200 total patients) and 185 traumatic brain injury (TBI) patients for a total of more than 54,000 pupillary measurements.ResultsStroke patients with at least 1 occurrence of an NPi differential during their NSICU stay have higher DC mRS scores (3.9) compared to those without an NPi differential (2.7; P < .001). Patients with TBI and at least 1 occurrence of an NPi differential during their NSICU stay have higher discharge modified Rankin Scale scores (4.1) compared to those without an NPi differential (2.9; P < .001). When patients experience both abnormalities, abnormal (NPi < 3.0) and an NPi differential, the latter has an anticipatory relationship with respect to the former (P < .001 for z-score skewness analysis). Finally, our analysis confirmed ≥ 0.7 as the optimal cutoff value for the NPi differential (AUC = 0.71, P < .001).ConclusionThe NPi differential is an important factor that clinicians should consider when managing critically ill neurological injured patients admitted to the neurocritical care units.Trial registrationNCT02804438, Date of Registration: June 17, 2016.

Automated Pupillometry as an Assessment Tool for Intracranial Hemodynamics in Septic Patients.

Impaired cerebral autoregulation (CA) may increase the risk of brain hypoperfusion in septic patients. Sepsis dysregulates the autonomic nervous system (ANS), potentially affecting CA. ANS function can be assessed through the pupillary light reflex (PLR). The aim of this prospective, observational study was to investigate the association between CA and PLR in adult septic patients. Transcranial Doppler was used to assess CA and calculate estimated cerebral perfusion pressure (eCPP) and intracranial pressure (eICP). An automated pupillometer (AP) was used to record Neurological Pupil Index (NPi), constriction (CV) and dilation (DV) velocities. The primary outcome was the relationship between AP-derived variables with CA; the secondary outcome was the association between AP-derived variables with eCPP and/or eICP. Among 40 included patients, 21 (53%) had impaired CA, 22 (55%) had low eCPP (<60 mmHg) and 15 (38%) had high eICP (>16 mmHg). DV was lower in patients with impaired CA compared to others; DV predicted impaired CA with area under the curve, AUROC= 0.78 [95% Confidence Interval, CI 0.63–0.94]; DV < 2.2 mm/s had sensitivity 85% and specificity 69% for impaired CA. Patients with low eCPP or high eICP had lower NPi values than others. NPi was correlated with eCPP (r = 0.77, p < 0.01) and eICP (r = −0.87, p < 0.01). Automated pupillometry may play a role to assess brain hemodynamics in septic patients.

Early Neurological Pupil Index Assessment to Predict Outcome in Cardiac Arrest Patients Undergoing Extracorporeal Membrane Oxygenation.

Early Neurological Pupil Index Assessment to Predict Outcome in Cardiac Arrest Patients Undergoing Extracorporeal Membrane Oxygenation.

Relationship Between Automated Pupillometry Measurements and Ventricular Volume in Patients With Aneurysmal Subarachnoid Hemorrhage.

INTRODUCTION: Pupillometry allows for a standardized assessment of the pupillary light reflex. Acute hydrocephalus (HCP) is a common complication in patients with aneurysmal subarachnoid hemorrhage (aSAH). HCP may affect the pupillary light reflex because of increased intracranial pressure or dilation of the rostral aqueduct. The association between the pupillary light reflex and HCP in aSAH patients has not been clearly established. The objective of this study is to analyze the correlation between the Neurological Pupil index (NPi) and the degree of HCP in aSAH patients. METHODS: The Establishing Normative Data for Pupillometer Assessments in Neuroscience Intensive Care Registry is a prospectively collected database of pupillometry readings in patients admitted to 4 different neurological intensive care units. Patients in the registry with aSAH who had pupillometry assessments within 6 hours of a brain computed tomography were studied. The degree of HCP was quantified using the HCP score, and the relationship between the NPi and HCP was analyzed after controlling for confounders. RESULTS: A total of 43 patients were analyzed (mean age, 54 ± 15 years; 53.2% male; mean HCP score, 5.3 ± 3.8). Thirty-eight patients had HCP. Mean NPi for the right eye was 4.02 (±1.2), and that for the left eye was 3.7 (±1.5). After adjusting for age, sex, race, and sedation, there was no significant correlation between HCP and NPi (right eye: r = 0.12, P = .44; left eye: r = 0.04, P = .8). CONCLUSION: In patients with aSAH, NPi was not correlated with HCP score. A small sample size could be a limitation of this study. Additional studies are needed to characterize the clinical significance of pupillometry in the evaluation of patients with aSAH and HCP.

Quantitative pupillometry in comatose out-of-hospital cardiac arrest patients: A post-hoc analysis of the TTH48 trial.

BackgroundQuantitative pupillometry is an objective method to examine pupil reaction and subsequently grade the response on a neurological pupil index (NPi) scale from 0 to 5. The aim of the present sub‐study was to explore the long‐term prognostic value of NPi in comatose out‐of‐hospital cardiac arrest patients undergoing targeted temperature management (TTM).MethodsThis planned sub‐study of the “Targeted temperature management for 48 versus 24 h and neurological outcome after out‐of‐hospital cardiac arrest: A randomized clinical trial.” NPi was assessed from admission and throughout day 3 and linked to the Cerebral Performance Categories score at 6 months. We compared the prognostic performance of NPi in 65 patients randomized to a target temperature of 33 ± 1°C for 24 or 48 h.ResultsThe NPi values were not different between TTM groups (p > .05). When data were pooled, NPi was strongly associated with neurological outcome at day 1 with a mean NPi of 3.6 (95% CI 3.4–3.8) versus NPi 3.9 (3.6–4.1) in the poor versus good outcome group, respectively (p < .01). At day 2, NPi values were 3.6 (3.1–4.0) and 4.1 (3.9–4.2) (p = .01) and at day 3, the values were 3.3 (2.6–4.0) and 4.3 (4.1–4.6), respectively (p < .01). The prognostic ability of NPi, defined by area under the receiver operating characteristic curve was best at day three.ConclusionQuantitative pupillometry measured by NPi was not different in the two TTM groups, but overall, significantly associated with good and poor neurological outcomes at 6 months. NPI has a promising diagnostic accuracy, but larger studies are warranted.

Can Quantitative Pupillometry be used to Screen for Elevated Intracranial Pressure? A Retrospective Cohort Study

BackgroundElevated intracranial pressure (ICP) is a serious complication in brain injury. Because of the risks involved, ICP is not monitored in all patients at risk. Noninvasive screening tools to identify patients with elevated ICP are needed. Anisocoria, abnormal pupillary size, and abnormal pupillary light reflex are signs of high ICP, but manual pupillometry is arbitrary and subject to interrater variability. We have evaluated quantitative pupillometry as a screening tool for elevated ICP.MethodsWe performed a retrospective observational study of the association between Neurological Pupil index (NPi), measured with the Neuroptics NPi-200 pupillometer, and ICP in patients routinely monitored with invasive ICP measurement in the intensive care unit. We performed a nonparametric receiver operator curve analysis for ICP ≥ 20 mm Hg with NPi as a classification variable. We performed a Youden analysis for the optimal NPi cutoff value and recorded sensitivity and specificity for this cutoff value. We also performed a logistic regression with elevated ICP as the dependent variable and NPi as the independent variable.ResultsWe included 65 patients with invasive ICP monitoring. A total of 2,705 measurements were analyzed. Using NPi as a screening tool for elevated ICP yielded an area under receiver operator curve of 0.72. The optimal mean NPi cutoff value to rule out elevated ICP was ≥ 3.9. The probability of elevated ICP decreased with increasing NPi, with an odds ratio of 0.55 (0.50, 0.61).ConclusionsScreening with NPi may inform high stakes clinical decisions by ruling out elevated ICP with a high degree of certainty. It may also aid in estimating probabilities of elevated ICP. This can help to weigh the risks of initiating invasive ICP monitoring against the risks of not doing so. Because of its ease of use and excellent interrater reliability, we suggest further studies of NPi as a screening tool for elevated ICP.

Dexmedetomidine and Other Analgosedatives Alter Pupil Characteristics in Critically Ill Patients.

OBJECTIVES:In critically ill patients with neurologic disease, pupil examination abnormalities can signify evolving intracranial pathology. Analgesic and sedative medications (analgosedatives) target pupillary pathways, but it remains unknown how analgosedatives alter pupil findings in the clinical care setting. We assessed dexmedetomidine and other analgosedative associations with pupil reactivity and size in a heterogeneous cohort of critically ill patients with acute intracranial pathology.DESIGN:Retrospective cohort study.SETTING:Two neurologic ICUs between 2016 and 2018.PATIENTS:Critically ill adult patients with pupil measurements within 60 minutes of analgosedative administration. Patients with a history of intrinsic retinal pathology, extracranial injury, inaccessible brain imaging, or no Glasgow Coma Scale (GCS) data were excluded.INTERVENTIONS:None.MEASUREMENTS AND MAIN RESULTS:We used mixed-effects linear regression accounting for intrapatient correlations and adjusting for sex, age, GCS score, radiographic mass effect, medication confounders, and ambient light. We tested the association between an initiation or increased IV infusion of dexmedetomidine and pupil reactivity (Neurologic Pupil Index [NPi]) and resting pupil size (mm) obtained using NeurOptics NPi—200 (NeurOptics, Irvine, CA) pupillometer. Of our 221 patients with 9,897 pupil observations (median age, 60 [interquartile range, 50–68]; 59% male), 37 patients (166 pupil observations) were exposed to dexmedetomidine. Dexmedetomidine was associated with higher average NPi (β = 0.18 per 1 unit increase in rank-normalized NPi ± 0.04; p < 0.001) and smaller pupil size (β = –0.25 ± 0.05; p < 0.001). Exploratory analyses revealed that acetaminophen was associated with higher average NPi (β = 0.04 ± 0.02; p = 0.02) and that most IV infusion analgosedatives including propofol, fentanyl, and midazolam were associated with smaller pupil size.CONCLUSIONS:Dexmedetomidine is associated with higher pupil reactivity (high NPi) and smaller pupil size in a cohort of critically ill patients with neurologic injury. Familiarity with expected pupil changes following analgosedative administration is important for accurate interpretation of pupil examination findings, facilitating optimal management of patients with acute intracranial pathology.

Neurological Pupil Index for the Early Prediction of Outcome in Severe Acute Brain Injury Patients.

In this study, we examined the early value of automated quantitative pupillary examination, using the Neurological Pupil index (NPi), to predict the long-term outcome of acute brain injured (ABI) patients. We performed a single-centre retrospective study (October 2016–March 2019) in ABI patients who underwent NPi measurement during the first 3 days following brain insult. We examined the performance of NPi—alone or in combination with other baseline demographic (age) and radiologic (CT midline shift) predictors—to prognosticate unfavourable 6-month outcome (Glasgow Outcome Scale 1–3). A total of 145 severely brain-injured subjects (65 traumatic brain injury, TBI; 80 non-TBI) were studied. At each time point tested, NPi <3 was highly predictive of unfavourable outcome, with highest specificity (100% (90–100)) at day 3 (sensitivity 24% (15–35), negative predictive value 36% (34–39)). The addition of NPi, from day 1 following ABI to age and cerebral CT scan, provided the best prognostic performance (AUROC curve 0.85 vs. 0.78 without NPi, p = 0.008; DeLong test) for 6-month neurological outcome prediction. NPi, assessed at the early post-injury phase, has a superior ability to predict unfavourable long-term neurological outcomes in severely brain-injured patients. The added prognostic value of NPi was most significant when complemented with baseline demographic and radiologic information.

Pilot Study of Neurologic Pupil Index as A Predictor of External Ventricular Drain Clamp Trial Failure After Subarachnoid Hemorrhage

External ventricular drains (EVDs) provide a temporary egress for cerebrospinal fluid (CSF) in patients with symptomatic hydrocephalus following aneurysmal subarachnoid hemorrhage. Before EVD removal, a wean trial, which involves clamping the EVD, is typically attempted to ensure that CSF self-regulation is achieved. Automated infrared pupillometry (AIP) has been shown to detect early neurologic decline. We sought to explore the use of AIP to detect early EVD clamping trial failure. This prospective observational pilot study enrolled aneurysmal subarachnoid hemorrhage patients before an EVD clamp trial. On initiating the clamp trial, nurses included hourly AIP assessment in documentation. Clamp trial outcome was based on neurologic examination and neuroimaging. Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) models were constructed to explore computed tomography (CT) versus AIP as predictors of clamp trial outcome. Among the 30 subjects enrolled, there were 38 clamping trials and 22 successful EVD removals. CT scan as a predictor of clamp trial was found to have a sensitivity of 68.8% and specificity of 89.5% (PPV= 84.6%, NPV= 77.3%). AIP assessment as a predictor of wean trial outcome was found to have a sensitivity of 58.3% and specificity of 100% (PPV= 100%, NPV= 63.2%). The pilot study data support that Neurological Pupil index <3 is a potential indicator of early clamp trial failure, but a CT scan has a higher sensitivity and NPV for predicting successful EVD removal. This finding suggests the benefits of including AIP assessments during clamping trials.

Pain pupillary index to prognosticate unfavorable outcome in comatose cardiac arrest patients

BackgroundThe prognostic role of the Pupillary Pain Index (PPI), derived from automated pupillometry, remains unknown in post-anoxic brain injury. MethodsSingle-center retrospective study in adult comatose cardiac arrest (CA) patients. Quantitative PPI and Neurologic Pupil Index (NPi) were concomitantly recorded on day 1 and day 2 after CA. The primary outcome was to assess the prognostic value of PPI to predict 3-month unfavourable outcome (UO, defined as Cerebral Performance Category of 3–5). Secondary outcome was the agreement between PPI and NPi to predict unfavourable outcome. ResultsA total of 102 patients were included; patients with UO (n = 69, 68%) showed a lower NPi (4.2 [3.5–4.5] vs. 4.6 [4.3–4.7]; p < 0.01 on day 1–4.3 [3.8–4.7] vs 4.6 [4.3–4.8] on day 2), and PPI (3 [1–6] vs. 6 [3–7]; p < 0.01 on day 1–3 [1–6] vs 6 [4–8]; p < 0.01 on day 2) than others. A PPI = 1 on day 2 showed a sensitivity of 26 [95% CI 16–38]% and a specificity of 100 [95% CI 89–100]% to predict UO (p = 0.003 vs. NPi ≤ 2). On day 2, a total of 6 patients had concomitant PPI = 1 and NPi ≤ 2, while 12 showed NPi > 2 and PPI = 1; the coefficient of agreement was 0.42. Moreover, NPi and PPI values showed a moderate correlation both on day 1 and day 2. ConclusionsIn this study, PPI = 1 on day 2 could predict UO in comatose CA patients with 100% specificity, but with a low sensitivity (yet higher than NPi). The agreement between PPI and NPi values was moderate.