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.

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.

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.

Vasoplegic Syndrome after Cardiopulmonary Bypass in Cardiovascular Surgery: Pathophysiology and Management in Critical Care.

Vasoplegic syndrome (VS) is a common complication following cardiovascular surgery with cardiopulmonary bypass (CPB), and its incidence varies from 5 to 44%. It is defined as a distributive form of shock due to a significant drop in vascular resistance after CPB. Risk factors of VS include heart failure with low ejection fraction, renal failure, pre-operative use of angiotensin-converting enzyme inhibitors, prolonged aortic cross-clamp and left ventricular assist device surgery. The pathophysiology of VS after CPB is multi-factorial. Surgical trauma, exposure to the elements of the CPB circuit and ischemia-reperfusion promote a systemic inflammatory response with the release of cytokines (IL-1ß, IL-6, IL-8, and TNF-α) with vasodilating properties, both direct and indirect through the expression of inducible nitric oxide (NO) synthase. The resulting increase in NO production fosters a decrease in vascular resistance and a reduced responsiveness to vasopressor agents. Further mechanisms of vasodilation include the lowering of plasma vasopressin, the desensitization of adrenergic receptors, and the activation of ATP-dependent potassium (KATP) channels. Patients developing VS experience more complications and have increased mortality. Management includes primarily fluid resuscitation and conventional vasopressors (catecholamines and vasopressin), while alternative vasopressors (angiotensin 2, methylene blue, hydroxocobalamin) and anti-inflammatory strategies (corticosteroids) may be used as a rescue therapy in deteriorating patients, albeit with insufficient evidence to provide any strong recommendation. In this review, we present an update of the pathophysiological mechanisms of vasoplegic syndrome complicating CPB and discuss available therapeutic options.

Hypertonic lactate for the treatment of intracranial hypertension in patients with acute brain injury.

Hypertonic lactate (HL) is emerging as alternative treatment of intracranial hypertension following acute brain injury (ABI), but comparative studies are limited. Here, we examined the effectiveness of HL on main cerebral and systemic physiologic variables, and further compared it to that of standard hypertonic saline (HS). Retrospective cohort analysis of ABI subjects who received sequential osmotherapy with 7.5% HS followed by HL-given at equi-osmolar (2400 mOsmol/L) and isovolumic (1.5 mL/kg) bolus doses-to reduce sustained elevations of ICP (> 20 mmHg). The effect of HL on brain (intracranial pressure [ICP], brain tissue PO2 [PbtO2], cerebral microdialysis [CMD] glucose and lactate/pyruvate ratio [LPR]) and blood (chloride, pH) variables was examined at different time-points (30, 60, 90, 120 min vs. baseline), and compared to that of HS. A total of 34 treatments among 17 consecutive subjects (13 traumatic brain injury [TBI], 4 non-TBI) were studied. Both agents significantly reduced ICP (p < 0.001, at all time-points tested): when comparing treatment effectiveness, absolute ICP decrease in mmHg and the duration of treatment effect (median time with ICP < 20 mmHg following osmotherapy 183 [108-257] vs. 150 [111-419] min) did not differ significantly between HL and HS (all p > 0.2). None of the treatment had statistically significant effects on PbtO2 and CMD biomarkers. Treatment with HL did not cause hyperchloremia and resulted in a more favourable systemic chloride balance than HS (Δ blood chloride - 1 ± 2.5 vs. + 4 ± 3 mmol/L; p < 0.001). This is the first clinical study showing that HL has comparative effectiveness than HS for the treatment of intracranial hypertension, while at the same time avoiding hyperchloremic acidosis. Both agents had no significant effect on cerebral oxygenation and metabolism.

Micronutrient Deficiencies in Medical and Surgical Inpatients.

Inpatients are threatened by global malnutrition, but also by specific micronutrient (i.e., trace element and vitamins) deficiencies that frequently are overseen in the differential diagnosis of major organ dysfunctions. Some of them are related to specific geographic risks (iodine, iron, selenium, zinc, vitamin A), while others are pathology related, and finally many are associated with specific feeding patterns, including low dose enteral feeding. Among the pathologies in which laboratory blood investigations should include a micronutrient outwork, anemia is in the front line, followed by obesity with bariatric surgery, chronic liver disease, kidney disease, inflammatory bowel disease, cardiomyopathies and heart failure. The micronutrients at the highest risk are iron, zinc, thiamine, vitamin B12 and vitamin C. Admission to hospital has been linked with an additional risk of malnutrition-feeding below 1500 kcal/day was frequent and has been associated with a structural additional risk of insufficient micronutrient intake to cover basal needs. Although not evidence based, systematic administration of liberal thiamine doses upon admission, and daily complementation of inpatients' food and enteral feeding solutions with multi-micronutrient tablets might be considered.

Copper Deficiency: Causes, Manifestations, and Treatment.

BACKGROUND: The metabolism of the essential trace element copper remains incompletely understood and, until recently, nearly ignored in acute medicine. Menkes disease was for long the only known copper deficiency condition, but several case reports and investigations conducted over the last 2 decades have shown that deficiency is more frequent than previously suspected, with devastating individual consequences and potential public health consequences. The copper needs in healthy individuals are 0.9 mg/d, which translates to 0.3 mg/d intravenously in parenteral nutrition; the present review aims at gathering actual knowledge. METHOD AND RESULTS: A review of literature was conducted in PubMed and Cochrane systematic reviews to identify the most recent information about copper deficiency and generate a narrative review. Copper deficiency has hereditary and acquired origins, the latter being the most frequent. Clinical manifestations are nonspecific but affect all organs and systems, particularly the hematologic (anemia) and the neurologic (myeloneuropathy) systems. Deficiency also affects the cardiovascular, cutaneous, and immune systems. Severe copper deficiency due to reduced absorption after bariatric bypass surgery has become frequent. CONCLUSION: Deficiency is more frequent than previously recognized, probably because of changing nutrition patterns but also because of some treatments that have become very common such as bypass bariatric surgery and, in acute medicine, prolonged continuous renal replacement therapy. The patients may present with severe hematologic and neurologic complications that go untreated because copper deficiency was not considered in the differential diagnosis: These complications often need active intravenous repletion with doses 4-8 times the usual nutrition recommendations.

Short-term propofol anaesthesia down-regulates clock genes expression in the master clock.

BACKGROUND: Propofol anesthesia triggers phase-advances of circadian rhythms controlled by the suprachiasmatic nuclei (SCN), the master clock. Besides, inhalational anesthesia has been associated with a subsequent reduction of Per2 mRNA levels in the whole brain of rodents. The acute effects of propofol anesthesia per se on the SCN molecular clockwork remain unclear. Here we aim to study the expression of Per1 and Per2 clock genes in the SCN of rats exposed to constant darkness after a single dose of propofol. METHODS: Thirty 2-months old rats were randomly divided into 2 groups receiving a single dose of either 120 mg/kg propofol 1% (n=15), or intralipid® 10% (n=15) in late day (projected circadian time (CT) 10, i.e., 10h after the expected time of lights on). Thereafter, rat brains were sampled in darkness 1h, 2h or 3h after the treatment (projected CT11, CT12 or CT13). Expression of Per1 and Per2 mRNA was analyzed by in situ hybridization in SCN coronal sections. RESULTS: Per1 expression was affected by time and treatment. Per1 expression in the SCN after propofol treatment decreased at CT11 and CT12 when compared to the vehicle group. For Per2 expression, we observed only a treatment effect. Observed in dark conditions without hypothermia or/and concomitant surgery, such down-regulation of clock genes Per is only correlated to propofol treatment. This may explain "jet-lag-like" symptoms described by patients after anesthesia. CONCLUSION: We show here for the first time that short-term propofol anesthesia leads to a transient down-regulation of Per1 and Per2 expression in the SCN.

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.