Venkatesh Aiyagari

BACKGROUND: Guidelines recommend the use of enteral nimodipine for 21 days after aneurysmal subarachnoid hemorrhage (aSAH). The recommended duration (21 d) and frequency of administration (every 4 h) may lead to noncompliance. Nurses play a critical role in medication administration, monitoring adverse reactions, and ensuring patient compliance with prescribed regimens. The aim of this study is to assess the degree of compliance with nimodipine use, causes of noncompliance and explore if adherence to nimodipine in clinical practice correlates with improved neurological outcomes as indicated by modified Rankin Scale (mRS) scores. METHODS: A retrospective study of consecutive aSAH admissions to a comprehensive stroke center over a 67-month period. Compliance was defined as receiving at least 80% of the recommended doses of nimodipine over 21 days. A chart review was performed to explore the reasons for noncompliance. We examined hospital disposition at discharge and 90-day mRS, adjusted for severity of aSAH. Compliance rates before and after a pharmacist-guided intervention were also examined. RESULTS: Among 141 patients, the overall compliance rate was just 30%. The leading reasons for missed doses included hypotension (68.1%) and patients being off the unit (56%). Compliance was not associated with improvement in 90-day mRS scores for low-grade aSAH ( P =0.3638) and high-grade aSAH ( P =0.227). After pharmacist-guided intervention, compliance improved from 18.2% to 43.8%. CONCLUSION: There is a high rate of noncompliance with nimodipine use in aSAH, but it did not significantly impact patient outcomes. Although pharmacist interventions improved compliance, full compliance remains challenging.

BACKGROUND: Changes in pupil reactivity secondary to cerebral mass effect are traditionally linked to compression of the oculomotor nerve by the uncus or by horizontal midbrain displacement. The neurological pupil index (NPi) is a metric to assess the pupillary light reflex. This study explores the relationship of midline shift, cisternal, and sulcal effacement or ventricular compression in patients with a new finding of abnormal pupillary light reflex. METHODS: This retrospective study identified adult patients with serial pupillometer readings between 2018 and 2023 who had a baseline head computed tomography (CT) scan, subsequent new-onset NPi worsening from normal to abnormal, and a repeat CT scan within 2 hours of the NPi changes. Those with NPi worsening were compared with those with no NPi change. RESULTS: Among 77 patients (27 with NPi worsening, 50 without), those with NPi worsening exhibited a higher incidence of midline shift on the repeat CT. Regression models revealed a significant correlation between midline shift change and abnormal NPi (r = 0.2260, P < .001). However, NPi worsening was not linked to changes in ventricular compression, nor sulcal or cisternal effacement. CONCLUSION: Midline shift, rather than cisternal or sulcal effacement, is associated with abnormal NPi values.

Background Assessing pupil size and reactivity is the standard of care in neurocritically ill patients. Anisocoria observed in critically ill patients often prompts further investigation and treatment. This study explores anisocoria at rest and after light stimulus determined using quantitative pupillometry as a predictor of discharge modified Rankin Scale (mRS) scores. Methods This analysis includes data from an international registry and includes patients with paired (left and right eye) quantitative pupillometry readings linked to discharge mRS scores. Anisocoria was defined as the absolute difference in pupil size using three common cut points (> 0.5 mm, > 1 mm, and > 2 mm). Nonparametric models were constructed to explore patient outcome using three predictors: the presence of anisocoria at rest (in ambient light); the presence of anisocoria after light stimulus; and persistent anisocoria (present both at rest and after light). The primary outcome was discharge mRS score associated with the presence of anisocoria at rest versus after light stimulus using the three commonly defined cut points. Results This analysis included 152,905 paired observations from 6,654 patients with a mean age of 57.0 (standard deviation 17.9) years, and a median hospital stay of 5 (interquartile range 3–12) days. The mean admission Glasgow Coma Scale score was 12.7 (standard deviation 3.5), and the median discharge mRS score was 2 (interquartile range 0–4). The ranges for absolute differences in pupil diameters were 0–5.76 mm at rest and 0–6.84 mm after light. Using an anisocoria cut point of > 0.5 mm, patients with anisocoria after light had worse median mRS scores (2 [interquartile range 0–4]) than patients with anisocoria at rest (1 [interquartile range 0–3]; P < .0001). Patients with persistent anisocoria had worse median mRS scores (3 [interquartile range 1–4]) than those without persistent anisocoria (1 [interquartile range 0–3]; P < .0001). Similar findings were observed using a cut point for anisocoria of > 1 mm and > 2 mm. Conclusions Anisocoria after light is a new biomarker that portends worse outcome than anisocoria at rest. After further validation, anisocoria after light should be considered for inclusion as a reported and trended assessment value.

Objectives The purpose of this pilot study was to obtain baseline quantitative pupillometry (QP) measurements before and after catheter-directed cerebral angiography (DCA) to explore the hypothesis that cerebral angiography is an independent predictor of change in pupillary light reflex (PLR) metrics. Design This was a prospective, observational pilot study of PLR assessments obtained using QP 30 min before and after DCA. All patients had QP measurements performed with the NPi-300 (Neuroptics) pupillometer. Setting Recruitment was done at a single-centre, tertiary-care academic hospital and comprehensive stroke centre in Dallas, Texas. Participants Fifty participants were recruited undergoing elective or emergent angiography. Inclusion criteria were a physician-ordered interventional neuroradiological procedure, at least 18 years of age, no contraindications to PLR assessment with QP, and nursing transport to and from DCA. Patients with a history of eye surgery were excluded. Main outcome measures Difference in PLR metric obtained from QP 30 min before and after DCA. Results Statistically significant difference was noted in the pre and post left eye readings for the minimum pupil size (a.k.a., pupil diameter on maximum constriction). The mean maximum constriction diameter prior to angiogram of 3.2 (1.1) mm was statistically larger than after angiogram (2.9 (1.0) mm; pConclusions Our study provides supportive data that in an uncomplicated angiogram, even with intervention, there is no effect on the PLR.

Background: Automated 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.Methods: We 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.Results: Stroke 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).Conclusion: The NPi differential is an important factor that clinicians should consider when managing critically ill neurological injured patients admitted to the neurocritical care units.Trial registration: NCT02804438, Date of Registration: June 17, 2016.

Introduction. The pupillary light reflex (PLR) is an integral aspect of the neurologic exam. With the enhancement of automated infrared pupillometry (AIP), the Neurological Pupil index (NPi) is being increasingly used when performing a neurological examination. NPi difference (the absolute difference between paired NPi readings from the left and right eye) is a relatively unexplored variable in AIP assessment.Aim. This study evaluates the association between Glasgow Coma Scale (GCS) scores and NPi differences between the left and right eyes, when the NPi is normal, in patients enrolled in a multi-center prospective database.Material and Methods. Restricting observations to only include NPi values ≥ 3 (normal), there were 2,572 qualifying patients with 3,519 pupillometer readings linked to GCS values. Linear regression and ANOVA models were developed to investigate the relationship between GCS and NPi difference.Results. Subject mean age was 55.88 (16.95) years and 54.5% were female. Mean NPi difference was 0.36 and mean GCS was 12.06. Regression analysis indicated a slight negative association between NPi difference and GCS (r2 = 0.0696, P < .0001). When observations were dichotomized as either NPi difference ≥ 0.7 (large) or < 0.7 (small), there was a statistically significant difference in the mean GCS (10.76 [3.90]) for large NPi difference vs. small NPi difference (13.15 [2.68]; P < .0001).Conclusions. Even among patients with normal PLR, a large NPi difference is associated with lower GCS scores. Trending and evaluating the NPi difference may become an important aspect of patient assessment. (JNNN 2021;10(4):168–174)

INTRODUCTION: Enteral nimodipine provides a neuroprotective effect in patients who have experienced an aneurysmal subarachnoid hemorrhage (aSAH). Nimodipine remains the only US Food and Drug Administration–approved medication for aSAH. CONTENT: Nimodipine has been prescribed for patients with aSAH; however, little is known about factors to consider regarding dosing or patient-specific variables that may affect tolerability to nimodipine. Clinical impact of dose or dosing frequency changes has also been much debated based on risk of hypotension with currently approved dosing regimens. CONCLUSION: This review article addresses factors to consider for dosing and administration, pharmacokinetic and pharmacogenetic impact on nimodipine, and, finally, drug interaction considerations to assess as patients are initiated on enteral nimodipine for aSAH.

Automated 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.