Early Metabolic Disruption and Predictive Biomarkers of Delayed-Cerebral Ischemia in Aneurysmal Subarachnoid Hemorrhage.

Delayed cerebral ischemia (DCI) following aneurysmal subarachnoid hemorrhage (aSAH) is a major cause of complications and death. Here, we set out to identify high-performance predictive biomarkers of DCI and its underlying metabolic disruptions using metabolomics and lipidomics approaches. This single-center prospective observational study enrolled 61 consecutive patients with severe aSAH; among them, 22 experienced a DCI. Nine patients without aSAH were included as validation controls. Blood and cerebrospinal fluid (CSF) were sampled within the first 24 h after admission. We identified a panel of 20 metabolites that, together, showed high predictive performance for DCI. This panel of metabolites included lactate, cotinine, salicylate, 6 phosphatidylcholines, and 4 sphingomyelins. The interplay of the metabolome and the lipidome found between CSF and plasma in our patients underscores that aSAH and its associated DCI complications can extend beyond cerebral implications, with a peripheral dimension as well. As an illustration, early biological disruptions that might explain the subsequent DCI found systemic hypoxia driven mainly by higher blood lactate, arginine, and proline metabolism likely associated with vascular NO and disrupted ceramide/sphingolipid metabolism. We conclude that targeting early peripheral hypoxia preceding DCI could provide an interesting strategy for the prevention of vascular dysfunction.

Comparison of scales for the evaluation of aneurysmal subarachnoid haemorrhage: a retrospective cohort study.

BACKGROUND/OBJECTIVES: Aneurysmal subarachnoid haemorrhage (aSAH) is a life-threatening event with major complications. Delayed cerebral infarct (DCI) occurs most frequently 7 days after aSAH and can last for a prolonged period. To determine the most predictive radiological scales in grading subarachnoid or ventricular haemorrhage or both for functional outcome at 3 months in a large aSAH population, we conducted a single-centre retrospective study. METHODS: A 3-year single-centre retrospective cohort study of 230 patients hospitalised for aSAH was analysed. Initial computed tomography (CT) scans in patients hospitalised for aSAH were blindly assessed using eight grading systems: the Fisher grade, modified Fisher grade, Barrow Neurological Institute scale, Hijdra scale, Intraventricular Haemorrhage (IVH) score, Graeb score and LeRoux score. RESULTS: Of 200 patients with aSAH who survived to day 7 and were included for DCI analysis, 39% of cases were complicated with DCI. The Hijdra scale was the best predictor for DCI, with a receiver operating characteristic area under the curve (ROCAUC) of 0.80 (95% confidence interval (CI), 0.74-0.85). The IVH score was the most effective grading system for predicting acute hydrocephalus, with a ROCAUC of 0.85 (95% CI, 0.79-0.89). In multivariate analysis, the Hijdra scale was the best predictor of the occurrence of DCI (hazard ratio, 1.18; 95% CI, 1.10-1.25). CONCLUSIONS: Although these results have yet to be prospectively confirmed, our findings suggest that the Hijdra scale may be a good predictor of DCI and could be useful in daily clinical practice. CLINICAL RELEVANCE STATEMENT: Better assessment of subarachnoid haemorrhage patients would allow for better prognostication and management of expectations, as well as referral for appropriate services and helping to appropriate use limited critical care resources. KEY POINTS: Aneurysmal subarachnoid haemorrhage is a life-threatening event that causes severe disability and leads to major complications such as delayed cerebral infarction. Accurate assessment of the amount of blood in the subarachnoid spaces on computed tomography with the Hijdra scale can better predict the risk of delayed cerebral infarct. The Hijdra scale could be a good triage tool for subarachnoid haemorrhage patients.

Contribution of an Automatic Algorithm for Quantifying the Volume of Aneurysmal Subarachnoid Hemorrhage to the Evaluation of the Risk of Occurrence of Delayed Cerebral Ischemia: A Cohort Study.

BACKGROUND: This study focuses on aneurysmal subarachnoid hemorrhage (aSAH) with a high risk of delayed cerebral ischemia (DCI) and acute hydrocephalus (AH). The aim was to compare the performance of an automatic algorithm for quantifying the volume of intracranial blood with the reference radiological scales to predict DCI, AH, and neurological outcome. METHODS: This was a single-center retrospective observational study of a cohort of patients with aSAH. We developed an automated blood detection algorithm based on the specific density of the blood clot. The blood clot was segmented on the first brain scan (total, supratentorial, cisternal, intraventricular). The predictive value of our model was compared, using the area under the receiver operating characteristic curve (ROCAUC), to eight radiological scales: Fisher, modified Fisher, Claassen, Barrow Neurological Institute, Hijdra, Graeb, LeRoux scales, and intraventricular hemorrhage score. RESULTS: We analyzed the scans of 145 patients with aSAH. In our cohort, 51 patients (43%) had DCI and 70 patients (54%) had AH. At 3 months, 22% of patients had died and 19% had poor outcome (Glasgow Outcome Scale extended 2-4). Cisternal blood volume was significantly correlated with cisternal Hijdra scale (R2 = 0.79; P < 0.001). The ROCAUC of cisternal blood volume was comparable to the ROCAUC of the Hijdra scale in predicting the occurrence of DCI (ROCAUC = 0.83 [95% confidence interval {CI} 0.75-0.89] vs. 0.86 [95% CI 0.79-0.9]; P = 0.23). The ROCAUC of intraventricular blood volume was not significantly different from the intraventricular hemorrhage score in predicting the occurrence of AH (ROCAUC = 0.78 [95% CI 0.70-0.84] vs. 0.79 [95% CI 0.72-0.85]; P = 0.28). The ROCAUC and supratentorial blood volumes were not significantly different from the Simplified Acute Physiology Score II in predicting the occurrence of poor neurological outcome at 3 months (ROCAUC = 0.75 [95% CI 0.67-0.82] vs. 0.81 [95% CI 0.74-0.87]; P = 0.073). CONCLUSIONS: With no manual intervention, our algorithm performed as well as the best radiological scores in predicting the occurrence of DCI, AH, and neurological outcome.

DNA Origami Assembled Nanoantennas for Manipulating Single-Molecule Spectral Emission.

The emission spectrum of a dye is given by the energy of all of the possible radiative transitions weighted by their probability. This spectrum can be altered with optical nanoantennas that are able to manipulate the decay rate of nearby emitters by modifying the local density of photonic states. Here, we make use of DNA origami to precisely place an individual dye at different positions around a gold nanorod and show how this affects the emission spectrum of the dye. In particular, we observe a strong suppression or enhancement of the transitions to different vibrational levels of the excitonic ground state, depending on the spectral overlap with the nanorod resonance. This reshaping can be used to experimentally extract the spectral dependence of the radiative decay rate enhancement. Furthermore, for some cases, we argue that the drastic alteration of the fluorescence spectrum could arise from the violation of Kasha's rule.

Predictive Modeling of COVID-19 Intensive Care Unit Patient Flows and Nursing Complexity: A Monte Carlo Simulation Study.

This study aimed to develop a Monte Carlo simulation model to forecast the number of ICU beds needed for COVID-19 patients and the subsequent nursing complexity in a French teaching hospital during the first and second pandemic outbreaks. The model used patient data from March 2020 to September 2021, including age, sex, ICU length of stay, and number of patients on mechanical ventilation or extracorporeal membrane oxygenation. Nursing complexity was assessed using a simple scale with three levels based on patient status. The simulation was performed 1000 times to generate a scenario, and the mean outcome was compared with the observed outcome. The model also allowed for a 7-day forecast of ICU occupancy. The simulation output had a good fit with the actual data, with an R2 of 0.998 and a root mean square error of 0.22. The study demonstrated the usefulness of the Monte Carlo simulation model for predicting the demand for ICU beds and could help optimize resource allocation during a pandemic. The model's extrinsic validity was confirmed using open data from the French Public Health Authority. This study provides a valuable tool for healthcare systems to anticipate and manage surges in ICU demand during pandemics.

The REACT study: design of a randomized phase 3 trial to assess the efficacy and safety of clazosentan for preventing deterioration due to delayed cerebral ischemia after aneurysmal subarachnoid hemorrhage.

BACKGROUND: For patients presenting with an aneurysmal subarachnoid hemorrhage (aSAH), delayed cerebral ischemia (DCI) is a significant cause of morbidity and mortality. The REACT study is designed to assess the safety and efficacy of clazosentan in preventing clinical deterioration due to DCI in patients with aSAH. METHODS: REACT is a prospective, multicenter, randomized phase 3 study that is planned to enroll 400 patients with documented aSAH from a ruptured cerebral aneurysm, randomized 1:1 to 15 mg/hour intravenous clazosentan vs. placebo, in approximately 100 sites and 15 countries. Eligible patients are required to present at hospital admission with CT evidence of significant subarachnoid blood, defined as a thick and diffuse clot that is more than 4 mm in thickness and involves 3 or more basal cisterns. The primary efficacy endpoint is the occurrence of clinical deterioration due to DCI up to 14 days post-study drug initiation. The main secondary endpoint is the occurrence of clinically relevant cerebral infarction at Day 16 post-study drug initiation. Other secondary endpoints include the modified Rankin Scale (mRS) and the Glasgow Outcome Scale-Extended (GOSE) score at Week 12 post-aSAH, dichotomized into poor and good outcome. Radiological results and clinical endpoints are centrally evaluated by independent committees, blinded to treatment allocation. Exploratory efficacy endpoints comprise the assessment of cognition status at 12 weeks and quality of life at 12 and 24 weeks post aSAH. DISCUSSION: In the REACT study, clazosentan is evaluated on top of standard of care to determine if it reduces the risk of clinical deterioration due to DCI after aSAH. The selection of patients with thick and diffuse clots is intended to assess the benefit/risk profile of clazosentan in a population at high risk of vasospasm-related ischemic complications post-aSAH. TRIAL REGISTRATION (ADDITIONAL FILE 1): ClinicalTrials.gov (NCT03585270). EU Clinical Trial Register (EudraCT Number: 2018-000241-39).

Perioperative Open-lung Approach, Regional Ventilation, and Lung Injury in Cardiac Surgery.

BACKGROUND: In the Protective Ventilation in Cardiac Surgery (PROVECS) randomized, controlled trial, an open-lung ventilation strategy did not improve postoperative respiratory outcomes after on-pump cardiac surgery. In this prespecified subanalysis, the authors aimed to assess the regional distribution of ventilation and plasma biomarkers of lung epithelial and endothelial injury produced by that strategy. METHODS: Perioperative open-lung ventilation consisted of recruitment maneuvers, positive end-expiratory pressure (PEEP) = 8 cm H2O, and low-tidal volume ventilation including during cardiopulmonary bypass. Control ventilation strategy was a low-PEEP (2 cm H2O) low-tidal volume approach. Electrical impedance tomography was used serially throughout the perioperative period (n = 56) to compute the dorsal fraction of ventilation (defined as the ratio of dorsal tidal impedance variation to global tidal impedance variation). Lung injury was assessed serially using biomarkers of epithelial (soluble form of the receptor for advanced glycation end-products, sRAGE) and endothelial (angiopoietin-2) lung injury (n = 30). RESULTS: Eighty-six patients (age = 64 ± 12 yr; EuroSCORE II = 1.65 ± 1.57%) undergoing elective on-pump cardiac surgery were studied. Induction of general anesthesia was associated with ventral redistribution of tidal volumes and higher dorsal fraction of ventilation in the open-lung than the control strategy (0.38 ± 0.07 vs. 0.30 ± 0.10; P = 0.004). No effect of the open-lung strategy on the dorsal fraction of ventilation was noted at the end of surgery after median sternotomy closure (open-lung = 0.37 ± 0.09 vs. control = 0.34 ± 0.11; P = 0.743) or in extubated patients at postoperative day 2 (open-lung = 0.63 ± 0.18 vs. control = 0.59 ± 0.11; P > 0.999). Open-lung ventilation was associated with increased intraoperative plasma sRAGE (7,677 ± 3,097 pg/ml vs. 6,125 ± 1,400 pg/ml; P = 0.037) and had no effect on angiopoietin-2 (P > 0.999). CONCLUSIONS: In cardiac surgery patients, open-lung ventilation provided larger dorsal lung ventilation early during surgery without a maintained benefit as compared with controls at the end of surgery and postoperative day 2 and was associated with higher intraoperative plasma concentration of sRAGE suggesting lung overdistension.

Surgical indications for pituitary tumors during pregnancy: a literature review.

PURPOSE: Surgical indications for pituitary tumors during pregnancy are rare, and are derived from a balance between expected benefits, particularly for maternal benefits, and anesthetic/surgical risks. METHODS: A literature review was performed to define the optimal surgical indications for pituitary adenomas (PA) and other pituitary tumors during pregnancy. RESULTS: Main benefits are expected in case of critical visual impairment and/or life-threatening endocrine disturbances. Multidisciplinary patient management is systematically required although nonobstetric surgery presents a reasonable risk during pregnancy. The risks of congenital malformation during the first trimester and those of premature birth during the third trimester make the second trimester the optimal period for surgery. In prolactin-secreting, nonsecreting, GH- and TSH-secreting PAs, transsphenoidal surgery (TS) is recommended in cases involving severe visual impairment, characterized by severe visual field deficit, visual acuity impairment, and abnormal optical coherence tomography findings, and when no other medical alternatives are possible and/or sufficient. Uncontrolled and severe Cushing's disease (CD) during pregnancy increases both maternal and fetal morbimortality, thus justifying TS or sometimes dopamine agonist therapy as a safer alternative. Finally, metyrapone, ketoconazole, or bilateral adrenalectomy could be recommended in certain cases after the failure of medical therapies and/or TS. Surgery is also required for suprasellar meningiomas, craniopharyngiomas, and pituitary cysts in the case of severe visual deficit. CONCLUSION: Surgical indications for pituitary tumors are rare during pregnancy; therefore, surgery should be avoided when possible. Further, the second trimester should be considered as the optimal surgical period. Severe visual disturbance and uncontrolled CD are the main surgical indications during pregnancy.

Thick and Diffuse Subarachnoid Blood as a Treatment Effect Modifier of Clazosentan After Subarachnoid Hemorrhage.

Background and Purpose- Clazosentan, an endothelin receptor antagonist, has been shown to reduce angiographic vasospasm and vasospasm-related morbidity after aneurysmal subarachnoid hemorrhage (SAH), although no effect on long-term functional outcome has been demonstrated. Thick clot on initial computed tomography is associated with an increased risk of vasospasm and delayed cerebral ischemia. In this post hoc analysis, we hypothesized that use of clazosentan in this subpopulation would provide stronger benefit. Methods- We analyzed SAH patients enrolled in the CONSCIOUS-2 and CONSCIOUS-3 studies (Clazosentan to Overcome Neurological Ischemia and Infarction Occurring After Subarachnoid Hemorrhage) and compared the effects of clazosentan 5 mg/h, 15 mg/h, and placebo starting the day after aneurysm repair. The analysis was performed separately based on the presence or absence of thick (≥4 mm) and diffuse (≥3 cisterns) SAH on admission computed tomography. The primary composite end point was all-cause mortality and vasospasm-related morbidity at 6 weeks, and the main secondary end point was the extended Glasgow Outcome Scale at 3 months, adjusted for admission clinical grade. Results- Of 1718 randomized patients, 919 (53%) had thick and diffuse SAH. The primary composite end point in this group occurred in 36% of placebo-treated patients (n=294), 30% patients treated with clazosentan 5 mg/h (n=514; relative risk, 0.82; 95% CI, 0.67-0.99), and 19% patients treated with clazosentan 15 mg/h (n=111; relative risk, 0.54; 95% CI, 0.36-0.80). Despite this, death or poor functional outcome (Glasgow Outcome Scale ≤4) occurred in 33% of placebo-treated patients, 34% of patients treated with clazosentan 5 mg/h (relative risk 1.02; 95% CI, 0.84-1.23), and 35% of patients treated with clazosentan 15 mg/h (relative risk 1.14; 95% CI, 0.88-1.48). Conclusions- In an enriched population with thick and diffuse SAH, clazosentan at a dose of 5 and 15 mg/h was able to significantly reduce vasospasm-related morbidity in a dose-dependent manner. The absence of an effect on long-term functional status likely reflects the complexity and multiplicity of factors that contribute to poor outcome after SAH. Clinical Trial Registration- URL: https://www.clinicaltrials.gov. Unique identifier: NCT00558311; NCT00940095.

Paired acute-baseline serum tryptase levels in perioperative anaphylaxis: An observational study.

BACKGROUND: Anaphylaxis is recognized mainly through clinical criteria, which may lack specificity or relevance in the perioperative setting. The transient increase in serum tryptase has been proposed since 1989 as a diagnostic tool. Sampling for well-defined acute and baseline determinations has been recommended. We assessed the performance of four proposed algorithms with tightly controlled time frames for tryptase sampling, their robustness with inadequate sampling times, and the possible use of mature tryptase determination. METHODS: A retrospective study was performed on 102 adult patients from the Aix-Marseille University Hospitals who had experienced a perioperative hypersensitivity reaction clinically suggesting anaphylaxis. EAACI and ICON criteria were used to diagnose anaphylaxis. Mature and total serum tryptase levels were measured. RESULTS: Based on EAACI guidelines, clinical diagnostic criteria for anaphylaxis were found in 76 patients and lacking in 26. The most effective algorithm was the international consensus recommendation of 2012 that acute total tryptase levels should be greater than ([1.2×baseline tryptase] + 2] µg/L to be considered a clinically significant rise. In our cohort, this algorithm achieved 94% positive predictive value (PPV), 53% negative predictive value (NPV), 75% sensitivity, 86% specificity, and a Youden's index value of 0.61. A detectable acute mature tryptase level showed lower sensitivity, particularly in patients with acute total tryptase levels lower than 16 µg/L. Acute tryptase levels varied as a function of the clinical severity of anaphylaxis. CONCLUSION: Total tryptase levels in serum discriminated between nonanaphylactic and anaphylactic events in a perioperative setting when acute and baseline levels were collected and analyzed by the consensus algorithm.

Thromboxane-prostaglandin receptor antagonist, terutroban, prevents neurovascular events after subarachnoid haemorrhage: a nanoSPECT study in rats.

BACKGROUND: Several lipid metabolites in cerebrospinal fluid are correlated with poor outcomes in aneurysmal subarachnoid haemorrhage. Most of these metabolites bind to ubiquitous thromboxane-prostaglandin (TP) receptors, causing vasoconstriction and inflammation. Here, we evaluated terutroban (TBN), a specific TP receptor antagonist, for the prevention of post-haemorrhage blood-brain barrier disruption, neuronal apoptosis and delayed cerebral hypoperfusion. METHODS: The rat double subarachnoid haemorrhage model was produced by twice injecting (days 1 and 2) autologous blood into the cisterna magna. Seventy-eight male Sprague-Dawley rats were assigned to experimental groups. Rats exposed to subarachnoid haemorrhage were allocated to no treatment (SAH group) or TBN treatment by gastric gavage during the first 5 days after haemorrhage (SAH+TBN group). Control rats received artificial cerebrospinal fluid injections (CSF group). Sham-operated rats with or without TBN administration were also studied. Body weight and Garcia neurological scores were assessed on day 2 and day 5. We used nanoscale single-photon emission computed tomography (nanoSPECT) to measure brain uptake of three radiolabelled agents: 99mTechnetium-diethylenetriaminepentacetate (99mTc-DTPA), which indicated blood-brain barrier permeability on day 3, 99mTechnetium-annexin V-128 (99mTc-Anx-V128), which indicated apoptosis on day 4, and 99mTechnetium-hexamethylpropyleneamineoxime (99mTc-HMPAO), which indicated cerebral perfusion on day 5. Basilar artery narrowing was verified histologically, and cerebral TP receptor agonists were quantified. RESULTS: 99mTc-DTPA uptake unveiled blood-brain barrier disruption in the SAH group. TBN mitigated this disruption in the brainstem area. 99mTc-Anx-V128 uptake was increased in the SAH group and TBN diminished this effect in the cerebellum. 99mTc-HMPAO uptake revealed a global decreased perfusion on day 5 in the SAH group that was significantly counteracted by TBN. TBN also mitigated basilar artery vasoconstriction, neurological deficits (on day 2), body weight loss (on day 5) and cerebral production of vasoconstrictors such as Thromboxane B2 and Prostaglandin F2α. CONCLUSIONS: Based on in vivo nanoscale imaging, we demonstrated that TBN protected against blood-brain barrier disruption, exerted an anti-apoptotic effect and improved cerebral perfusion. Thus, TP receptor antagonists showed promising results in treating post-haemorrhage neurovascular events.

Prediction Score for Postoperative Neurologic Complications after Brain Tumor Craniotomy: A Multicenter Observational Study.

WHAT WE ALREADY KNOW ABOUT THIS TOPIC: WHAT THIS ARTICLE TELLS US THAT IS NEW: BACKGROUND:: Craniotomy for brain tumor displays significant morbidity and mortality, and no score is available to discriminate high-risk patients. Our objective was to validate a prediction score for postoperative neurosurgical complications in this setting. METHODS: Creation of a score in a learning cohort from a prospective specific database of 1,094 patients undergoing elective brain tumor craniotomy in one center from 2008 to 2012. The validation cohort was validated in a prospective multicenter independent cohort of 830 patients from 2013 to 2015 in six university hospitals in France. The primary outcome variable was postoperative neurologic complications requiring in-intensive care unit management (intracranial hypertension, intracranial bleeding, status epilepticus, respiratory failure, impaired consciousness, unexpected motor deficit). The least absolute shrinkage and selection operator method was used for potential risk factor selection with logistic regression. RESULTS: Severe complications occurred in 125 (11.4%) and 90 (10.8%) patients in the learning and validation cohorts, respectively. The independent risk factors for severe complications were related to the patient (Glasgow Coma Score before surgery at or below 14, history of brain tumor surgery), tumor characteristics (greatest diameter, cerebral midline shift at least 3 mm), and perioperative management (transfusion of blood products, maximum and minimal systolic arterial pressure, duration of surgery). The positive predictive value of the score at or below 3% was 12.1%, and the negative predictive value was 100% in the learning cohort. In-intensive care unit mortality was observed in eight (0.7%) and six (0.7%) patients in the learning and validation cohorts, respectively. CONCLUSIONS: The validation of prediction scores is the first step toward on-demand intensive care unit admission. Further research is needed to improve the score's performance before routine use.

Peri-operative oral caffeine does not prevent postoperative atrial fibrillation after heart valve surgery with cardiopulmonary bypass: A randomised controlled clinical trial.

BACKGROUND: Raised plasma levels of endogenous adenosine after cardiac surgery using cardiopulmonary bypass (CPB) have been related to the incidence of postoperative atrial fibrillation (POAF). OBJECTIVE: We wished to assess if caffeine, an adenosine receptor antagonist could have a beneficial effect on the incidence of POAF. DESIGN: A randomised controlled study. SETTING: Single University Hospital. PATIENTS: One hundred and ten patients scheduled for heart valve surgery with CPB. INTERVENTIONS: We randomly assigned patients to receive peri-operative oral caffeine (400 mg every 8 h for 2 days) or placebo. Adenosine plasma concentrations and caffeine pharmacokinetic profile were evaluated in a subgroup of 50 patients. MAIN OUTCOME MEASURES: The primary endpoint was the rate of atrial fibrillation during postoperative hospital stay. RESULTS: The current study was stopped for futility by the data monitoring board after an interim analysis. The incidence of atrial fibrillation was similar in the caffeine and in the placebo group during hospital stay (33 vs. 29%, P = 0.67) and the first 3 postoperative days (18 vs. 15%; P = 0.60). Basal and postoperative adenosine plasma levels were significantly associated with the primary outcome. Adenosine plasma levels were similar in the two treatment groups. Caffeine administration was associated with a higher incidence of postoperative nausea and vomiting (27 vs. 7%, P = 0.005). CONCLUSION: Oral caffeine does not prevent POAF after heart valve surgery with CPB but increased the incidence of postoperative nausea and vomiting. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, no.: NCT01999829.

Reliability of standard pupillometry practice in neurocritical care: an observational, double-blinded study.

BACKGROUND: In critical care units, pupil examination is an important clinical parameter for patient monitoring. Current practice is to use a penlight to observe the pupillary light reflex. The result seems to be a subjective measurement, with low precision and reproducibility. Several quantitative pupillometer devices are now available, although their use is primarily restricted to the research setting. To assess whether adoption of these technologies would benefit the clinic, we compared automated quantitative pupillometry with the standard clinical pupillary examination currently used for brain-injured patients. METHODS: In order to determine inter-observer agreement of the device, we performed repetitive measurements in 200 healthy volunteers ranging in age from 21 to 58 years, providing a total of 400 paired (alternative right eye, left eye) measurements under a wide variety of ambient light condition with NeuroLight Algiscan pupillometer. During another period, we conducted a prospective, observational, double-blinded study in two neurocritical care units. Patients admitted to these units after an acute brain injury were included. Initially, nursing staff measured pupil size, anisocoria and pupillary light reflex. A blinded physician subsequently performed measurement using an automated pupillometer. RESULTS: In 200 healthy volunteers, intra-class correlation coefficient for maximum resting pupil size was 0.95 (IC: 0.93-0.97) and for minimum pupil size after light stimulation 0.87 (0.83-0.89). We found only 3-pupil asymmetry (≥ 1 mm) in these volunteers (1.5% of the population) with a clear pupil asymmetry during clinical inspection. The mean pupil light reactivity was 40 ± 7%. In 59 patients, 406 pupillary measurements were prospectively performed. Concordance between measurements for pupil size collected using the pupillometer, versus subjective assessment, was poor (Spearmen's rho = 0.75, IC: 0.70-0.79; P < 0.001). Nursing staff failed to diagnose half of the cases (15/30) of anisocoria detected using the pupillometer device. A global rate of discordance of 18% (72/406) was found between the two techniques when assessing the pupillary light reflex. For measurements with small pupils (diameters <2 mm) the error rate was 39% (24/61). CONCLUSION: Standard practice in pupillary monitoring yields inaccurate data. Automated quantitative pupillometry is a more reliable method with which to collect pupillary measurements at the bedside.