Cisternal nicardipine for prevention of delayed cerebral ischemia in aneurysmal subarachnoid hemorrhage: a comparative retrospective cohort study.

PURPOSE: Intrathecal vasoactive drugs have been proposed in patients with aneurysmal subarachnoid hemorrhage (aSAH) to manage cerebral vasospasm (CV). We analyzed the efficacy of intracisternal nicardipine compared to intraventricular administration to a control group (CG) to determine its impact on delayed cerebral ischemia (DCI) and functional outcomes. Secondary outcomes included the need for intra-arterial angioplasties and the safety profile. METHODS: We performed a retrospective analysis of prospectively collected data of all adult patients admitted for a high modified Fisher grade aSAH between January 2015 and April 2022. All patients with significant radiological CV were included. Three groups of patients were defined based on the CV management: cisternal nicardipine (CN), ventricular nicardipine (VN), and no intrathecal nicardipine (control group). RESULTS: Seventy patients met the inclusion criteria. Eleven patients received intracisternal nicardipine, 18 intraventricular nicardipine, and 41 belonged to the control group. No cases of DCI were observed in the CN group (p = 0.02). Patients with intracisternal nicardipine had a reduced number of intra-arterial angioplasties when compared to the control group (p = 0.03). The safety profile analysis showed no difference in complications across the three groups. Intrathecal (ventricular or cisternal) nicardipine therapy improved functional outcomes at 6 months (p = 0.04) when compared to the control group. CONCLUSION: Administration of intrathecal nicardipine for moderate to severe CV reduces the rate of DCI and improved long-term functional outcomes in patients with high modified Fisher grade aSAH. This study also showed a relative benefit of cisternal over intraventricular nicardipine, thereby reducing the number of angioplasties performed in the post-treatment phase. However, these preliminary results should be confirmed with future prospective studies.

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.

Multimodal Prediction of Favorable Outcome After Cardiac Arrest: A Cohort Study.

OBJECTIVES: Prognostic guidelines after cardiac arrest (CA) focus on unfavorable outcome prediction; favorable outcome prognostication received less attention. Our aim was to identify favorable outcome predictors and combine them into a multimodal model. DESIGN: Retrospective analysis of prospectively collected data (January 2016 to June 2021). SETTING: Two academic hospitals (Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland; Brigham and Women's Hospital, Boston, MA). PATIENTS: Four hundred ninety-nine consecutive comatose adults admitted after CA. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: CA variables (initial rhythm, time to return of spontaneous circulation), clinical examination (Full Outline of UnResponsiveness [FOUR] score at 72 hr, early myoclonus), electroencephalography (EEG) (reactivity, continuity, epileptiform features, and prespecified highly malignant patterns), somatosensory-evoked potentials, quantified pupillometry, and serum neuron-specific enolase (NSE) were retrieved. Neurologic outcome was assessed at 3 months using Cerebral Performance Category (CPC); 1 and 2 were considered as favorable outcome. Predictive performance of each variable toward favorable outcomes were calculated, and most discriminant items were combined to obtain a multimodal prognostic score, using multivariable ordinal logistic regression, receiving operator characteristic curves, and cross-validation. Our analysis identified a prognostic score including six modalities (1 point each): 1) early (12-36 hr) EEG not highly malignant, 2) early EEG background reactivity, 3) late (36-72 hr) EEG background reactivity and 4) continuity, 5) peak serum NSE within 48 hours less than or equal to 41 µg/L, and 6) FOUR score greater than or equal to 5 at 72 hours. At greater than or equal to 4 out of 6 points, sensitivity for CPC 1-2 was 97.5% (95% CI, 92.9-99.5%) and accuracy was 77.5% (95% CI, 72.7-81.8%); area under the curve was 0.88 (95% CI, 0.85-0.91). The score showed similar performances in the validation cohort. CONCLUSIONS: This study describes and externally validates a multimodal score, including clinical, EEG and biological items available within 72 hours, showing a high performance in identifying early comatose CA survivors who will reach functional independence at 3 months.

[Alpha-2 adrenoreceptor agonists for the intensive care physician]. / Les agonistes α2-adrénergiques pour l'intensiviste.

Clonidine and dexmedetomidine are two α2-adrenoreceptors agonists available for the intensivist in the clinical practice. The affinity of dexmedetomidine is eight times greater than clonidine affinity for the α2 receptors. Their main effect is sedation. They act by inhibition of noradrenaline release in the locus coeruleus in the brainstem. α2-agonists are used primarily for sedation, analgesia, and management of delirium. Nowadays, dexmedetomidine application is increasing in critically ill patients showing a good safety. Most frequent side effects include bradycardia and hypotension.

En pratique clinique, l'intensiviste dispose de deux α2-agonistes, à savoir la clonidine et la dexmédétomidine. L'affinité de la dexmédétomidine pour les récepteurs α2-adrénergiques est huit fois plus importante que celle de la clonidine. Leur principal effet est la sédation. Cet effet est obtenu par inhibition de la libération de noradrénaline dans le locus cœruleus du tronc cérébral. Ces molécules sont surtout utilisées pour la sédation, l'analgésie et la prise en charge du delirium chez le patient critique. Le recours à la dexmédétomidine augmente actuellement et montre une bonne sécurité de la molécule. Les effets indésirables les plus fréquents sont la bradycardie et l'hypotension.

Neuroprognostication Under ECMO After Cardiac Arrest: Are Classical Tools Still Performant?

BACKGROUND: According to international guidelines, neuroprognostication in comatose patients after cardiac arrest (CA) is performed using a multimodal approach. However, patients undergoing extracorporeal membrane oxygenation (ECMO) may have longer pharmacological sedation and show alteration in biological markers, potentially challenging prognostication. Here, we aimed to assess whether routinely used predictors of poor neurological outcome also exert an acceptable performance in patients undergoing ECMO after CA. METHODS: This observational retrospective study of our registry includes consecutive comatose adults after CA. Patients deceased within 36 h and not undergoing prognostic tests were excluded. Veno-arterial ECMO was initiated in patients < 80 years old presenting a refractory CA, with a no flow < 5 min and a low flow ≤ 60 min on admission. Neuroprognostication test performance (including pupillary reflex, electroencephalogram, somatosensory-evoked potentials, neuron-specific enolase) toward mortality and poor functional outcome (Cerebral Performance Categories [CPC] score 3-5) was compared between patients undergoing ECMO and those without ECMO. RESULTS: We analyzed 397 patients without ECMO and 50 undergoing ECMO. The median age was 65 (interquartile range 54-74), and 69.8% of patients were men. Most had a cardiac etiology (67.6%); 52% of the patients had a shockable rhythm, and the median time to return of an effective circulation was 20 (interquartile range 10-28) minutes. Compared with those without ECMO, patients receiving ECMO had worse functional outcome (74% with CPC scores 3-5 vs. 59%, p = 0.040) and a nonsignificant higher mortality (60% vs. 47%, p = 0.080). Apart from the neuron-specific enolase level (higher in patients with ECMO, p < 0.001), the presence of prognostic items (pupillary reflex, electroencephalogram background and reactivity, somatosensory-evoked potentials, and myoclonus) related to unfavorable outcome (CPC score 3-5) in both groups was similar, as was the prevalence of at least any two such items concomitantly. The specificity of each these variables toward poor outcome was between 92 and 100% in both groups, and of the combination of at least two items, it was 99.3% in patients without ECMO and 100% in those with ECMO. The predictive performance (receiver operating characteristic curve) of their combination toward poor outcome was 0.822 (patients without ECMO) and 0.681 (patients with ECMO) (p = 0.134). CONCLUSIONS: Pending a prospective assessment on a larger cohort, in comatose patients after CA, the performance of prognostic factors seems comparable in patients with ECMO and those without ECMO. In particular, the combination of at least two poor outcome criteria appears valid across these two groups.

[How to reduce the risk of orotracheal intubation in intensive care medicine?] / Comment réduire les risques de l'intubation orotrachéale en médecine intensive†?

Intubation is a frequent procedure in the intensive care unit, often performed in an emergency. Because of patients' clinical condition with little physiological reserve, intubation in the critically ill patients is associated with increased risk of complications. A systematic patient's assessment and a codified and rigorous preparation of the team and equipment significantly reduce the risks of intubation. The purpose of this article is to summarize the different strategies that allow maximizing safety of intubation in the critically ill.

L'intubation est un geste technique fréquent en médecine intensive, souvent réalisé en urgence ou semi-urgence. Il s'agit d'une procédure à risque de complications du fait des faibles réserves physiologiques des patients de médecine intensive au moment du geste. Une évaluation systématisée du patient avant l'intubation ainsi que la préparation rigoureuse de l'équipe et du matériel permettent d'anticiper les problèmes pouvant survenir lors de l'intubation et de réduire les risques associés à la procédure. Cet article a pour objectif de présenter les différentes stratégies permettant d'optimiser la sécurité lors de l'intubation orotrachéale en médecine intensive.

[Transforming operating rooms into an intensive care unit to manage the COVID-19 outbreak]. / Transformation du bloc opératoire en unité de soins intensifs pour gérer la pandémie de Covid-19.

This article is a descriptive analysis of the organizational steps undertaken to transform eight OR (operating rooms) of the University Hospital Lausanne CHUV into a dedicated ICU (intensive care unit) during the COVID-19 pandemic. An efficient response of our institution was mandatory to timely increase the number of ICU beds. The transformation of an entire floor of a functioning operating ward was deemed the most appropriate solution to provide rapidly a significant number of beds. The newly created ICU was the first additional ICU to open and admitted its first patient 48 hours after the beginning of the transformation.

Cet article résume les étapes organisationnelles entreprises pour transformer huit salles d'opération en une unité de soins intensifs pendant la pandémie de Covid-19. Une réponse efficace de notre institution était obligatoire pour augmenter en temps opportun le nombre de lits en soins intensifs. La transformation d'un étage entier d'un bloc opératoire fonctionnel a été jugée la solution la plus appropriée pour offrir le plus rapidement possible un nombre de lits conséquent. La nouvelle unité de soins intensifs adultes (SIA) a été la première unité de soins intensifs supplémentaire à ouvrir et a admis son premier patient 48 heures après le début des transformations.

Trace element and vitamin deficiency: quantum medicine or essential prescription?

PURPOSE OF REVIEW: In critical care, micronutrients remain perceived as 'quantum' part, that is, a little pertinent component of therapy. Some micronutrients have attracted more attention because of their antioxidant properties. During the last decade, some large size trials have tested their therapeutic potential, generally as 'single high-dose micronutrient intervention', with variable success. This review aims at taking stock of most recent. RECENT FINDINGS: Micronutrient blood levels are generally low in ICU patients, which has prompted the concept of replenishing or compensating deficits, or even realizing a pharmacological action. Single micronutrient trials have been conducted in large cohorts with selenium (≥1000 µg/day), with limited success but no harm. Other trials have tested high-dose vitamin D (>400 000 IU), with nonconvincing results despite selecting patients with very low blood levels. High-dose vitamin C has been tested in septic shock (+/- thiamine, hydrocortisone) with variable results. A problem encountered in all studies is definition of deficiency based on blood levels as majority of the patients suffer inflammation, which causes redistribution of the micronutrients away from the circulating compartment in the absence of real deficiency. SUMMARY: Micronutrients are essential in the ICU. Due to their antioxidant properties and to the high prevalence of low blood concentrations suggestive of deficiency, several large-size RCTs have been conducted with variable success. Further research must clarify the respective importance of deficiency and inflammation.

Neuromonitoring of delirium with quantitative pupillometry in sedated mechanically ventilated critically ill patients.

BACKGROUND: Intensive care unit (ICU) delirium is a frequent secondary neurological complication in critically ill patients undergoing prolonged mechanical ventilation. Quantitative pupillometry is an emerging modality for the neuromonitoring of primary acute brain injury, but its potential utility in patients at risk of ICU delirium is unknown. METHODS: This was an observational cohort study of medical-surgical ICU patients, without acute or known primary brain injury, who underwent sedation and mechanical ventilation for at least 48 h. Starting at day 3, automated infrared pupillometry-blinded to ICU caregivers-was used for repeated measurement of the pupillary function, including quantitative pupillary light reflex (q-PLR, expressed as % pupil constriction to a standardized light stimulus) and constriction velocity (CV, mm/s). The relationship between delirium, using the CAM-ICU score, and quantitative pupillary variables was examined. RESULTS: A total of 59/100 patients had ICU delirium, diagnosed at a median 8 (5-13) days from admission. Compared to non-delirious patients, subjects with ICU delirium had lower values of q-PLR (25 [19-31] vs. 20 [15-28] %) and CV (2.5 [1.7-2.8] vs. 1.7 [1.4-2.4] mm/s) at day 3, and at all additional time-points tested (p < 0.05). After adjusting for the SOFA score and the cumulative dose of analgesia and sedation, lower q-PLR was associated with an increased risk of ICU delirium (OR 1.057 [1.007-1.113] at day 3; p = 0.03). CONCLUSIONS: Sustained abnormalities of quantitative pupillary variables at the early ICU phase correlate with delirium and precede clinical diagnosis by a median 5 days. These findings suggest a potential utility of quantitative pupillometry in sedated mechanically ventilated ICU patients at high risk of delirium.

[Vasopressin in the critically ill patient]. / La vasopressine chez le patient en état critique.

Vasopressin (AVP) is a posterior pituitary hormone initially known for its antidiuretic actions. In this article, we recall the biochemical and pharmacological characteristics of the AVP and its analogues. Currently, its main indication in critical care medicine is vasoplegic shock in view of its vasopressive properties. This strong vasopressive activity is related to the activation of V1 receptors located in the vascular smooth muscle. The scientific evidence of the AVP therapy, and its potential benefits versus norepinephrine in vasoplegic shock, is reviewed in this article. Similarly, we present the other indications of vasopressin in the critical patient, based on recent studies and international guidelines.

La vasopressine (AVP) est une hormone post-hypophysaire connue initialement pour ses effets antidiurétiques. Dans cet article de synthèse, nous rappelons les particularités biochimiques et pharmacologiques de l'AVP et de ses analogues. De nos jours, sa principale indication en médecine intensive est le choc vasoplégique, eu égard à ses propriétés vasopressives qui sont liées à l'activation des récepteurs V1 du muscle lisse des vaisseaux sanguins, résultant en une puissante vasoconstriction. L'évidence scientifique de l'apport de l'AVP, et de ses bénéfices potentiels par rapport à la noradrénaline dans le choc vasoplégique, est revue en détail dans cet article. De même, nous présentons les autres indications de la vasopressine chez le patient en état critique, sur la base des études récentes et les recommandations des sociétés savantes.

Electroencephalography Predicts Poor and Good Outcomes After Cardiac Arrest: A Two-Center Study.

OBJECTIVE: The prognostic role of electroencephalography during and after targeted temperature management in postcardiac arrest patients, relatively to other predictors, is incompletely known. We assessed performances of electroencephalography during and after targeted temperature management toward good and poor outcomes, along with other recognized predictors. DESIGN: Cohort study (April 2009 to March 2016). SETTING: Two academic hospitals (Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland; Mayo Clinic, Rochester, MN). PATIENTS: Consecutive comatose adults admitted after cardiac arrest, identified through prospective registries. INTERVENTIONS: All patients were managed with targeted temperature management, receiving prespecified standardized clinical, neurophysiologic (particularly, electroencephalography during and after targeted temperature management), and biochemical evaluations. MEASUREMENTS AND MAIN RESULTS: We assessed electroencephalography variables (reactivity, continuity, epileptiform features, and prespecified "benign" or "highly malignant" patterns based on the American Clinical Neurophysiology Society nomenclature) and other clinical, neurophysiologic (somatosensory-evoked potential), and biochemical prognosticators. Good outcome (Cerebral Performance Categories 1 and 2) and mortality predictions at 3 months were calculated. Among 357 patients, early electroencephalography reactivity and continuity and flexor or better motor reaction had greater than 70% positive predictive value for good outcome; reactivity (80.4%; 95% CI, 75.9-84.4%) and motor response (80.1%; 95% CI, 75.6-84.1%) had highest accuracy. Early benign electroencephalography heralded good outcome in 86.2% (95% CI, 79.8-91.1%). False positive rates for mortality were less than 5% for epileptiform or nonreactive early electroencephalography, nonreactive late electroencephalography, absent somatosensory-evoked potential, absent pupillary or corneal reflexes, presence of myoclonus, and neuron-specific enolase greater than 75 µg/L; accuracy was highest for early electroencephalography reactivity (86.6%; 95% CI, 82.6-90.0). Early highly malignant electroencephalography had an false positive rate of 1.5% with accuracy of 85.7% (95% CI, 81.7-89.2%). CONCLUSIONS: This study provides class III evidence that electroencephalography reactivity predicts both poor and good outcomes, and motor reaction good outcome after cardiac arrest. Electroencephalography reactivity seems to be the best discriminator between good and poor outcomes. Standardized electroencephalography interpretation seems to predict both conditions during and after targeted temperature management.

LLL 44-1 Micronutrients in clinical nutrition: Trace elements.

BACKGROUND: Trace elements are an essential component of metabolism and medical nutrition therapy, with key roles in metabolic pathways, antioxidation, and immunity, which the present course aims at summarizing. RESULTS: Medical nutrition therapy includes the provision of all essential trace elements. The clinical essential issues are summarized for Copper, Iron, Selenium, Zinc, Iodine, Chromium, Molybdenum, and Manganese: the optimal analytical techniques are presented. The delivery of all these elements occurs nearly automatically when the patient is fed with enteral nutrition, but always requires separate prescription in case of parenteral nutrition. Isolated deficiencies may occur, and some patients have increased requirements, therefore a regular monitoring is required. The clinicians should always consider the impact of inflammation on blood levels, mostly lowering them even in absence of deficiency. CONCLUSION: This text summarises the most relevant clinical manifestations of trace element depletion and deficiency, the difficulties in assessing status, and makes practical recommendations for provision for enteral and parenteral nutrition.

[Hyperlactatemia and lactic acidosis in the critically ill patient]. / Hyperlactatémie et acidose lactique chez le patient critique.

Hyperlactatemia is associated with an ominous prognosis in critical illness and must be rapidly detected. Lactate is produced by glycolysis through reduction of pyruvate, itself oxidized in the mitochondria. It is transported to the liver and converted to glucose through gluconeogenesis (Cori's cycle). Hyperlactatemia can result from excessive production or reduced clearance. Excess production can occur in aerobic conditions, following an increase in pyruvate generation, or in anaerobic conditions, due to impaired pyruvate oxidation. Reduced lactate clearance occurs as a result of liver hypoperfusion or hepatic failure. Lactate/pyruvate ratio, as well as the concomitant existence of metabolic acidosis (lactic acidosis), help distinguish the different mechanisms leading to hyperlactatemia, which are reviewed in detail in this article.

Benign EEG for prognostication of favorable outcome after cardiac arrest: A reappraisal.

AIM: The current EEG role for prognostication after cardiac arrest (CA) essentially aims at reliably identifying patients with poor prognosis ("highly malignant" patterns, defined by Westhall et al. in 2014). Conversely, "benign EEGs", defined by the absence of elements of "highly malignant" and "malignant" categories, has limited sensitivity in detecting good prognosis. We postulate that a less stringent "benign EEG" definition would improve sensitivity to detect patients with favorable outcomes. METHODS: Retrospectively assessing our registry of unconscious adults after CA (1.2018-8.2021), we scored EEGs within 72 h after CA using a modified "benign EEG" classification (allowing discontinuity, low-voltage, or reversed anterio-posterior amplitude development), versus Westhall's "benign EEG" classification (not allowing the former items). We compared predictive performances towards good outcome (Cerebral Performance Category 1-2 at 3 months), using 2x2 tables (and binomial 95% confidence intervals) and proportions comparisons. RESULTS: Among 381 patients (mean age 61.9 ± 15.4 years, 104 (27.2%) females, 240 (62.9%) having cardiac origin), the modified "benign EEG" definition identified a higher number of patients with potential good outcome (252, 66%, vs 163, 43%). Sensitivity of the modified EEG definition was 0.97 (95% CI: 0.92-0.97) vs 0.71 (95% CI: 0.62-0.78) (p < 0.001). Positive predictive values (PPV) were 0.53 (95% CI: 0.46-0.59) versus 0.59 (95% CI: 0.51-0.67; p = 0.17). Similar statistics were observed at definite recording times, and for survivors. DISCUSSION: The modified "benign EEG" classification demonstrated a markedly higher sensitivity towards favorable outcome, with minor impact on PPV. Adaptation of "benign EEG" criteria may improve efficient identification of patients who may reach a good outcome.

Relationship between serum neuron-specific enolase and EEG after cardiac arrest: A reappraisal.

OBJECTIVE: Electroencephalogram (EEG) and serum neuron specific enolase (NSE) are frequently used prognosticators after cardiac arrest (CA). This study explored the association between NSE and EEG, considering the role of EEG timing, its background continuity, reactivity, occurrence of epileptiform discharges, and pre-defined malignancy degree. METHODS: Retrospective analysis including 445 consecutive adults from a prospective registry, surviving the first 24 hours after CA and undergoing multimodal evaluation. EEG were interpreted blinded to NSE results. RESULTS: Higher NSE was associated with poor EEG prognosticators, such as increasing malignancy, repetitive epileptiform discharges and lack of background reactivity, independently of EEG timing (including sedation and temperature). When stratified for background continuity, NSE was higher with repetitive epileptiform discharges, except in the case of suppressed EEGs. This relationship showed some variation according to the recording time. CONCLUSIONS: Neuronal injury after CA, reflected by NSE, correlates with several EEG features: increasing EEG malignancy, lack of background reactivity, and presence of repetitive epileptiform discharges. The correlation between epileptiform discharges and NSE is influenced by underlying EEG background and timing. SIGNIFICANCE: This study, describing the complex interplay between serum NSE and epileptiform features, suggests that epileptiform discharges reflect neuronal injury particularly in non-suppressed EEG.

Outcome of comatose patients following cardiac arrest: When mRS completes CPC.

AIM: Good outcome in patients following cardiac arrest (CA) is usually defined as Cerebral Performance Category (CPC) 1-2, while CPC 3 is debated, and CPC 4-5 represent poor outcome. We aimed to assess when the modified Rankin Scale (mRS) can improve CPC outcome description, especially in CPC 3. We further aimed to correlate neuron specific enolase (NSE) with both functional measures to explore their relationship with neuronal damage. METHODS: Peak NSE within the first 48 hours, and CPC and mRS at 3 months were prospectively collected for 665 consecutive comatose adults following CA treated between April 2016 and April 2023. For each CPC category, mRS was described. We considered good outcome as mRS 1-3, in line with existing recommendations. CPC and mRS were correlated to peak serum NSE using non-parametric assessments. RESULTS: CPC 1, 2, 4 and 5 correlated almost perfectly with mRS in terms of good and poor outcomes. However, CPC 3 was heterogeneously associated to the dichotomized mRS (53.1% had good outcome (mRS 0-3), 46.9% poor outcome (mRS 4-6)). NSE was strongly correlated with CPC (Spearman's rho 0.616, P < 0.001) and mRS (Spearman's rho 0.613, P < 0.001). CONCLUSION: CPC and mRS correlate similarly with neuronal damage. Whilst CPC 1-2 and CPC 4-5 are strongly associated with mRS 0-3 and, respectively, with mRS 5-6, CPC 3 is heterogenous: both good and poor mRS scores are found within this category. Therefore, we suggest that the mRS should be routinely assessed in patients with CPC 3 to refine outcome description.

The Neurological Pupil index for outcome prognostication in people with acute brain injury (ORANGE): a prospective, observational, multicentre cohort study.

BACKGROUND: Improving the prognostication of acute brain injury is a key element of critical care. Standard assessment includes pupillary light reactivity testing with a hand-held light source, but findings are interpreted subjectively; automated pupillometry might be more precise and reproducible. We aimed to assess the association of the Neurological Pupil index (NPi)-a quantitative measure of pupillary reactivity computed by automated pupillometry-with outcomes of patients with severe non-anoxic acute brain injury. METHODS: ORANGE is a multicentre, prospective, observational cohort study at 13 hospitals in eight countries in Europe and North America. Patients admitted to the intensive care unit after traumatic brain injury, aneurysmal subarachnoid haemorrhage, or intracerebral haemorrhage were eligible for the study. Patients underwent automated infrared pupillometry assessment every 4 h during the first 7 days after admission to compute NPi, with values ranging from 0 to 5 (with abnormal NPi being <3). The co-primary outcomes of the study were neurological outcome (assessed with the extended Glasgow Outcome Scale [GOSE]) and mortality at 6 months. We used logistic regression to model the association between NPi and poor neurological outcome (GOSE ≤4) at 6 months and Cox regression to model the relation of NPi with 6-month mortality. This study is registered with ClinicalTrials.gov, NCT04490005. FINDINGS: Between Nov 1, 2020, and May 3, 2022, 514 patients (224 with traumatic brain injury, 139 with aneurysmal subarachnoid haemorrhage, and 151 with intracerebral haemorrhage) were enrolled. The median age of patients was 61 years (IQR 46-71), and the median Glasgow Coma Scale score on admission was 8 (5-11). 40 071 NPi measurements were taken (median 40 per patient [20-50]). The 6-month outcome was assessed in 497 (97%) patients, of whom 160 (32%) patients died, and 241 (47%) patients had at least one recording of abnormal NPi, which was associated with poor neurological outcome (for each 10% increase in the frequency of abnormal NPi, adjusted odds ratio 1·42 [95% CI 1·27-1·64]; p<0·0001) and in-hospital mortality (adjusted hazard ratio 5·58 [95% CI 3·92-7·95]; p<0·0001). INTERPRETATION: NPi has clinically and statistically significant prognostic value for neurological outcome and mortality after acute brain injury. Simple, automatic, repeat automated pupillometry assessment could improve the continuous monitoring of disease progression and the dynamics of outcome prediction at the bedside. FUNDING: NeurOptics.

Continuous versus routine EEG in patients after cardiac arrest: Analysis of a randomized controlled trial (CERTA).

BACKGROUND: Electroencephalography (EEG) is essential to assess prognosis in patients after cardiac arrest (CA). Use of continuous EEG (cEEG) is increasing in critically-ill patients, but it is more resource-consuming than routine EEG (rEEG). Observational studies did not show a major impact of cEEG versus rEEG on outcome, but randomized studies are lacking. METHODS: We analyzed data of the CERTA trial (NCT03129438), including comatose adults after CA undergoing cEEG (30-48 hours) or two rEEG (20-30 minutes each). We explored correlations between recording EEG type and mortality (primary outcome), or Cerebral Performance Categories (CPC, secondary outcome), assessed blindly at 6 months, using uni- and multivariable analyses (adjusting for other prognostic variables showing some imbalance across groups). RESULTS: We analyzed 112 adults (52 underwent rEEG, 60 cEEG,); 31 (27.7%) were women; 68 (60.7%) patients died. In univariate analysis, mortality (rEEG 59%, cEEG 65%, p = 0.318) and good outcome (CPC 1-2; rEEG 33%, cEEG 27%, p = 0.247) were comparable across EEG groups. This did not change after multiple logistic regressions, adjusting for shockable rhythm, time to return of spontaneous circulation, serum neuron-specific enolase, EEG background reactivity, regarding mortality (cEEG vs rEEG: OR 1.60, 95% CI 0.43-5.83, p = 0.477), and good outcome (OR 0.51, 95% CI 0.14-1.90, p = 0.318). CONCLUSION: This analysis suggests that cEEG or repeated rEEG are related to comparable outcomes of comatose patients after CA. Pending a prospective, large randomized trial, this finding does not support the routine use of cEEG for prognostication in this setting. TRIAL REGISTRATION: Continuous EEG Randomized Trial in Adults (CERTA); NCT03129438; July 25, 2019.