Systemic inflammation and delirium during critical illness.

PURPOSE: The purpose of this study was to determine associations between markers of inflammation and endogenous anticoagulant activity with delirium and coma during critical illness. METHODS: In this prospective cohort study, we enrolled adults with respiratory failure and/or shock treated in medical or surgical intensive care units (ICUs) at 5 centers. Twice per day in the ICU, and daily thereafter, we assessed mental status using the Richmond Agitation Sedation Scale (RASS) and the Confusion Assessment Method-Intensive Care Unit (CAM-ICU). We collected blood samples on study days 1, 3, and 5, measuring levels of C-reactive protein (CRP), interferon gamma (IFN-γ), interleukin (IL)-1 beta (IL-1ß), IL-6, IL-8, IL-10, IL-12, matrix metalloproteinase-9 (MMP-9), tumor necrosis factor-alpha (TNF-α), tumor necrosis factor receptor 1 (TNFR1), and protein C using validated protocols. We used multinomial logistic regression to analyze associations between biomarkers and the odds of delirium or coma versus normal mental status the following day, adjusting for age, sepsis, Sequential Organ Failure Assessment (SOFA), study day, corticosteroids, and sedatives. RESULTS: Among 991 participants with a median age (interquartile range, IQR) of 62 [53-72] years and enrollment SOFA of 9 [7-11], higher concentrations of IL-6 (odds ratio [OR] [95% CI]: 1.8 [1.4-2.3]), IL-8 (1.3 [1.1-1.5]), IL-10 (1.5 [1.2-1.8]), TNF-α (1.2 [1.0-1.4]), and TNFR1 (1.3 [1.1-1.6]) and lower concentrations of protein C (0.7 [0.6-0.8])) were associated with delirium the following day. Higher concentrations of CRP (1.4 [1.1-1.7]), IFN-γ (1.3 [1.1-1.5]), IL-6 (2.3 [1.8-3.0]), IL-8 (1.8 [1.4-2.3]), and IL-10 (1.5 [1.2-2.0]) and lower concentrations of protein C (0.6 [0.5-0.8]) were associated with coma the following day. IL-1ß, IL-12, and MMP-9 were not associated with mental status. CONCLUSION: Markers of inflammation and possibly endogenous anticoagulant activity are associated with delirium and coma during critical illness.

Mild Hypercapnia or Normocapnia after Out-of-Hospital Cardiac Arrest.

BACKGROUND: Guidelines recommend normocapnia for adults with coma who are resuscitated after out-of-hospital cardiac arrest. However, mild hypercapnia increases cerebral blood flow and may improve neurologic outcomes. METHODS: We randomly assigned adults with coma who had been resuscitated after out-of-hospital cardiac arrest of presumed cardiac or unknown cause and admitted to the intensive care unit (ICU) in a 1:1 ratio to either 24 hours of mild hypercapnia (target partial pressure of arterial carbon dioxide [Paco2], 50 to 55 mm Hg) or normocapnia (target Paco2, 35 to 45 mm Hg). The primary outcome was a favorable neurologic outcome, defined as a score of 5 (indicating lower moderate disability) or higher, as assessed with the use of the Glasgow Outcome Scale-Extended (range, 1 [death] to 8, with higher scores indicating better neurologic outcome) at 6 months. Secondary outcomes included death within 6 months. RESULTS: A total of 1700 patients from 63 ICUs in 17 countries were recruited, with 847 patients assigned to targeted mild hypercapnia and 853 to targeted normocapnia. A favorable neurologic outcome at 6 months occurred in 332 of 764 patients (43.5%) in the mild hypercapnia group and in 350 of 784 (44.6%) in the normocapnia group (relative risk, 0.98; 95% confidence interval [CI], 0.87 to 1.11; P = 0.76). Death within 6 months after randomization occurred in 393 of 816 patients (48.2%) in the mild hypercapnia group and in 382 of 832 (45.9%) in the normocapnia group (relative risk, 1.05; 95% CI, 0.94 to 1.16). The incidence of adverse events did not differ significantly between groups. CONCLUSIONS: In patients with coma who were resuscitated after out-of-hospital cardiac arrest, targeted mild hypercapnia did not lead to better neurologic outcomes at 6 months than targeted normocapnia. (Funded by the National Health and Medical Research Council of Australia and others; TAME ClinicalTrials.gov number, NCT03114033.).

Brain-dead and coma patients exhibit different serum metabolic profiles: preliminary investigation of a novel diagnostic approach in neurocritical care.

There is a clear difference between severe brain damage and brain death. However, in clinical practice, the differentiation of these states can be challenging. Currently, there are no laboratory tools that facilitate brain death diagnosis. The aim of our study was to evaluate the utility of serum metabolomic analysis in differentiating coma patients (CP) from individuals with brain death (BD). Serum samples were collected from 23 adult individuals with established diagnosis of brain death and 24 patients in coma with Glasgow Coma Scale 3 or 4, with no other clinical symptoms of brain death for at least 7 days after sample collection. Serum metabolomic profiles were investigated using proton nuclear magnetic resonance (NMR) spectroscopy. The results obtained were examined by univariate and multivariate data analysis (PCA, PLS-DA, and OPLS-DA). Metabolic profiling allowed us to quantify 43 resonance signals, of which 34 were identified. Multivariate statistical modeling revealed a highly significant separation between coma patients and brain-dead individuals, as well as strong predictive potential. The findings not only highlight the potential of the metabolomic approach for distinguishing patients in coma from those in the state of brain death but also may provide an understanding of the pathogenic mechanisms underlying these conditions.

Serum NSE and S100B protein levels for evaluating the impaired consciousness in patients with acute carbon monoxide poisoning.

ABSTRACT: The aim of this study was to investigate the associations between the levels of neuron-specific enolase (NSE) and S100B protein and coma duration, and evaluate the optimal cut-off values for prediction coma duration ≥ 72 hours in patients with acute carbon monoxide poisoning (ACOP).A total of 60 patients with ACOP were divided into 3 following groups according to their status of consciousness and coma duration at admission: Awake group [Glasgow Coma Scale score (GCS score) ≥ 13 points], Coma < 72 hours group (GCS score < 13 points and coma duration < 72 h), and Coma ≥ 72 hours group (GCS score < 13 points and coma duration ≥ 72 h). The levels of serum NSE and S100B protein were measured after admission.There were significant differences in GCS score, carbon monoxide (CO) exposure time, NSE, and S100B levels between the Coma ≥ 72 h group and the Awake group, and between the Coma < 72 h group and the Awake group. Significant differences in GCS score, NSE, and S100B levels were also found between Coma ≥ 72 h group and Coma < 72 h group. Correlation analysis showed that NSE and S100B were positively correlated (rs = 0.590, P < .01); NSE and S100B were negatively correlated with GCS score (rs = -0.583, rs = -0.590, respectively, both P < .01). The areas under the curve (AUCs) of NSE, S100B, and GCS score to predict the coma duration ≥ 72 hours were 0.754, 0.791, and 0.785, respectively. Pairwise comparisons did not show differences among the 3 groups (all P > .05). The sensitivity and specificity of NSE prediction with a cut-off value of 13 µg/L were 80% and 64%, respectively, and those of S100B prediction with a cut-off value of 0.43 µg/L were 70% and 88%, respectively.The NSE and S100B protein levels were significantly correlated with the degree of impaired consciousness and had the same clinical value in predicting coma duration of ≥ 72 hours in patients with ACOP.

Relationships between serum levels of lactate dehydrogenase and neurological outcomes of patients who underwent targeted temperature management after out-of-hospital cardiac arrest.

ABSTRACT: This study aimed to evaluate times for measuring serum lactate dehydrogenase levels (SLLs) to predict neurological prognosis among out-of-hospital cardiac arrest (OHCA) survivors.This retrospective study examined patients who experienced OHCA treated with targeted temperature management (TTM). The SLLs were evaluated at the return of spontaneous circulation (ROSC) and at 24, 48, and 72 hours later. Neurological outcomes after 3 months were evaluated for relationships with the SLL measurement times.A total of 95 comatose patients with OHCA were treated using TTM. Seventy three patients were considered eligible, including 31 patients (42%) who experienced good neurological outcomes. There were significant differences between the good and poor outcome groups at most time points (P < .001), except for ROSC (P = .06). The ROSC measurement had a lower area under the receiver operating characteristic curve (AUC: 0.631, 95% confidence interval [CI]: 0.502-0.761) than at 48 hours (AUC: 0.830, 95% CI: 0.736-0.924), at 24 hours (AUC: 0.786, 95% CI: 0.681-0.892), and at 72 hours (AUC: 0.821, 95% CI: 0.724-0.919).A higher SLL seemingly predicted poor neurological outcomes, with good prognostic values at 48 hours and 72 hours. Prospective studies should be conducted to confirm these results.

Predictive Value and Correlation of Neuron-Specific Enolase for Prognosis in Patients with Coma: A Systematic Review and Meta-Analysis.

OBJECTIVE: Coma is the most serious disturbance of consciousness, which affects the life quality of patients and increases the burden of their family. Studies to assess the prognostic value of neuron-specific enolase (NSE) in patients with coma have not led to precise, generally accepted prognostic rules. The study aims to assess the correlation between NSE and prognosis of coma and the predictive value of NSE for clinical prognosis. METHODS: A search was conducted using PubMed, Web of Science, EMBASE, Cochrane Library, China National Knowledge Infrastructure (CNKI), and WanFang Data from the establishment time of databases to December 2019. This analysis included patients with coma, regardless of how long the coma was. In total, 26 articles were retrieved and included in the review. RESULTS: The meta-analysis revealed the NSE concentration of patients with coma is significantly higher than that of the control group (standard mean difference = 0.88, 95% confidence interval [CI]: 0.63-1.12, p < 0.05). The pooled sensitivity and specificity of NSE in coma diagnosis was 0.5 (95% CI: 0.39-0.61) and 0.86 (95% CI: 0.71-0.94). CONCLUSIONS: The NSE concentration of patients with poor coma prognosis is significantly higher than that of the control group. The high NSE concentration is not necessarily a poor prognosis for coma, but low NSE concentration indicates a high probability of a good prognosis for coma.

[An acidosis not so basic]. / Une acidose pas si basique.

We present the case of a four-year-old girl, who was hospitalized in intensive care unit for a coma resulting from metabolic acidosis with increased anion gap. The patient was treated for short bowel syndrome, following necrotising enterocolitis, which occurred 51 days after birth. In our initial evaluation of the patient's metabolic acidosis, we were unable to identify the cause of the increased anion gap. Urinary organic acids chromatography identified a large peak of lactate (quantified at 15 mmol/mol of creatiniuria), as well as its metabolites. The discrepancy between normal blood lactate concentration assayed by enzymatic assay, and the large amount of lactate found by gas-chromatography/mass spectrometry (GC/MS) in urine highlights the limit of the stereospecificity of enzymatic assays. Indeed, most lactates assay use enzymatic assays that are specific for L-lactate, whereas organic acids chromatography, whose column is mostly achiral, can detect both stereoisomers, D- and L-lactate. Organic acids in urine analysis, in addition to the clinical context, suggested a diagnosis of D-lactic acidosis. Following a review of the physiopathology and treatment of short bowel syndrome, we will discuss the mechanism and diagnosis of the D-lactic acidosis in our patient. This case highlights the need to perform an organic acid profile in urine in the presence of any unexplained increased anion gap to determine its cause.

Prediction of regaining consciousness despite an early epileptiform EEG after cardiac arrest.

OBJECTIVE: After cardiac arrest (CA), epileptiform EEG, occurring in about 1/3 of patients, often but not invariably heralds poor prognosis. We tested the hypothesis that a combination of specific EEG features identifies patients who may regain consciousness despite early epileptiform patterns. METHODS: We retrospectively analyzed a registry of comatose patients post-CA (2 Swiss centers), including those with epileptiform EEG. Background and epileptiform features in EEGs 12-36 hours or 36-72 hours from CA were scored according to the American Clinical Neurophysiology Society nomenclature. Best Cerebral Performance Category (CPC) score within 3 months (CPC 1-3 vs 4-5) was the primary outcome. Significant EEG variables were combined in a score assessed with receiver operating characteristic curves, and independently validated in a US cohort; its correlation with serum neuron-specific enolase (NSE) was also tested. RESULTS: Of 488 patients, 107 (21.9%) had epileptiform EEG <72 hours; 18 (17%) reached CPC 1-3. EEG 12-36 hours background continuity ≥50%, absence of epileptiform abnormalities (p < 0.00001 each), 12-36 and 36-72 hours reactivity (p < 0.0001 each), 36-72 hours normal background amplitude (p = 0.0004), and stimulus-induced discharges (p = 0.0001) correlated with favorable outcome. The combined 6-point score cutoff ≥2 was 100% sensitive (95% confidence interval [CI], 78%-100%) and 70% specific (95% CI, 59%-80%) for CPC 1-3 (area under the curve [AUC], 0.98; 95% CI, 0.94-1.00). Increasing score correlated with NSE (ρ = -0.46, p = 0.0001). In the validation cohort (41 patients), the score was 100% sensitive (95% CI, 60%-100%) and 88% specific (95% CI, 73%-97%) for CPC 1-3 (AUC, 0.96; 95% CI, 0.91-1.00). CONCLUSION: Prognostic value of early epileptiform EEG after CA can be estimated combining timing, continuity, reactivity, and amplitude features in a score that correlates with neuronal damage.

Association of diabetic ketoacidosis and HbA1c at onset with year-three HbA1c in children and adolescents with type 1 diabetes: Data from the International SWEET Registry.

OBJECTIVE: To establish whether diabetic ketoacidosis (DKA) or HbA1c at onset is associated with year-three HbA1c in children with type 1 diabetes (T1D). METHODS: Children with T1D from the SWEET registry, diagnosed <18 years, with documented clinical presentation, HbA1c at onset and follow-up were included. Participants were categorized according to T1D onset: (a) DKA (DKA with coma, DKA without coma, no DKA); (b) HbA1c at onset (low [<10%], medium [10 to <12%], high [≥12%]). To adjust for demographics, linear regression was applied with interaction terms for DKA and HbA1c at onset groups (adjusted means with 95% CI). Association between year-three HbA1c and both HbA1c and presentation at onset was analyzed (Vuong test). RESULTS: Among 1420 children (54% males; median age at onset 9.1 years [Q1;Q3: 5.8;12.2]), 6% of children experienced DKA with coma, 37% DKA without coma, and 57% no DKA. Year-three HbA1c was lower in the low compared to high HbA1c at onset group, both in the DKA without coma (7.1% [6.8;7.4] vs 7.6% [7.5;7.8], P = .03) and in the no DKA group (7.4% [7.2;7.5] vs 7.8% [7.6;7.9], P = .01), without differences between low and medium HbA1c at onset groups. Year-three HbA1c did not differ among HbA1c at onset groups in the DKA with coma group. HbA1c at onset as an explanatory variable was more closely associated with year-three HbA1c compared to presentation at onset groups (P = .02). CONCLUSIONS: Year-three HbA1c is more closely related to HbA1c than to DKA at onset; earlier hyperglycemia detection might be crucial to improving year-three HbA1c.

Decrease in Butyrylcholinesterase Accompanied by Intermediate-like Syndrome after Massive Ingestion of a Glyphosate-surfactant.

An 86-year-old woman intentionally drank approximately 300 mL of a glyphosate-surfactant. She was found with consciousness disturbance and experienced several vomiting episodes. On arrival, serum biochemistry revealed a decreased level of butyrylcholinesterase (B-CHE) [11 (normal range: 180-450) IU/L]. Later, her B-CHE level further decreased to single-digit values, and she became comatose with involuntary movement and an increase in muscle tone. Her consciousness level and muscle tone improved with the recovery of her B-CHE level. Physicians should be alert for the occurrence of intermediate syndrome when the B-CHE levels of patients who have consumed a massive amount of glyphosate-surfactant show a prolonged decrease.

Myxedema coma precipitated by diabetic ketoacidosis after total thyroidectomy: a case report.

BACKGROUND: Myxedema coma is profound decompensated hypothyroidism usually precipitated by stressors, and its occurrence in association with total thyroidectomy or metabolic disorders, such as diabetic ketoacidosis, is unusual. CASE PRESENTATION: A 43-year-old Asian man with history of total thyroidectomy who was scheduled for a second radioactive iodine therapy presented to our hospital with decreased mental status and hyperglycemia. He had a history of thyroid cancer but did not have diabetes mellitus. He was in a hypothermic state and had a Glasgow Coma Scale score of 10 out of 15 at presentation; arterial blood gas analysis revealed a state of metabolic acidosis and laboratory findings suggested hyperglycemia with glycosuria, ketoacidosis, and severe hypothyroidism. A thyroid function test showed thyroid-stimulating hormone of 34.126 uIU/mL, free thyroxine of 1.02 ng/dL, and triiodothyronine of 1.04 ng/mL. The glycated hemoglobin of this patient was checked due to hyperglycemia and the value of glycated hemoglobin was 16.5% which met the criteria for a diagnosis of diabetes. After treatment for myxedema with liothyronine 5 mcg two times per day and levothyroxine 175 mcg once daily via a nasogastric tube and diabetic ketoacidosis with intravenously administered fluid and insulin, his clinical condition rapidly improved including mental status, hyperglycemia, and acidosis. During the hospitalization, a workup for diabetes mellitus was performed and the results suggested that a diagnosis of type 2 diabetes mellitus would be appropriate. CONCLUSIONS: This case demonstrated that diabetic ketoacidosis not only could be a potential contributor to myxedema coma but also mask typical clinical features, making diagnosis more difficult. Considering the possibility of an increasing number of potential patients with hypothyroidism developed after thyroidectomy, constant vigilance is required for a better clinical outcome, including early recognition and management in critical care in advance for unusual diabetic ketoacidosis which could precipitate decompensated hypothyroidism.

Developing a personalized closed-loop controller of medically-induced coma in a rodent model.

OBJECTIVE: Personalized automatic control of medically-induced coma, a critical multi-day therapy in the intensive care unit, could greatly benefit clinical care and further provide a novel scientific tool for investigating how the brain response to anesthetic infusion rate changes during therapy. Personalized control would require real-time tracking of inter- and intra-subject variabilities in the brain response to anesthetic infusion rate while simultaneously delivering the therapy, which has not been achieved. Current control systems for medically-induced coma require a separate offline model fitting experiment to deal with inter-subject variabilities, which would lead to therapy interruption. Removing the need for these offline interruptions could help facilitate clinical feasbility. In addition, current systems do not track intra-subject variabilities. Tracking intra-subject variabilities is essential for studying whether or how the brain response to anesthetic infusion rate changes during therapy. Further, such tracking could enhance control precison and thus help facilitate clinical feasibility. APPROACH: Here we develop a personalized closed-loop anesthetic delivery (CLAD) system in a rodent model that tracks both inter- and intra-subject variabilities in real time while simultaneously controlling the anesthetic in closed loop. We tested the CLAD in rats by administrating propofol to control the electroencephalogram (EEG) burst suppression. We first examined whether the CLAD can remove the need for offline model fitting interruption. We then used the CLAD as a tool to study whether and how the brain response to anesthetic infusion rate changes as a function of changes in the depth of medically-induced coma. Finally, we studied whether the CLAD can enhance control compared with prior systems by tracking intra-subject variabilities. MAIN RESULTS: The CLAD precisely controlled the EEG burst suppression in each rat without performing offline model fitting experiments. Further, using the CLAD, we discovered that the brain response to anesthetic infusion rate varied during control, and that these variations correlated with the depth of medically-induced coma in a consistent manner across individual rats. Finally, tracking these variations reduced control bias and error by more than 70% compared with prior systems. SIGNIFICANCE: This personalized CLAD provides a new tool to study the dynamics of brain response to anesthetic infusion rate and has significant implications for enabling clinically-feasible automatic control of medically-induced coma.

Postoperative myxedema coma in patients undergoing major surgery: Case series.

OBJECTIVE: Myxedema coma is a serious complication of hypothyroidism that can be precipitated by major surgery. It is extremely rare, with only a few reports in the literature. This study aims to present a relatively large case series of post-surgical myxedema coma and to analyze medical and surgical risk factors. METHODS: Analysis of the patients' surgical records and medical charts. RESULTS: Four patients developed postoperative myxedema coma and were evaluated for risk factors. Three had known hypothyroidism. Two had undergone large head and neck composite resections necessitating a free flap repair for malignant disease. One had undergone coronary artery bypass graft for ischemic heart disease, and another had undergone endoscopic cholecystectomy for complicated cholecystitis. All four patients required prolonged hospitalization, including treatment in the intensive care unit. One patient had undergone full cardiopulmonary resuscitation directly related to the myxedema coma state. CONCLUSION: We present a series of four patients who developed myxedema coma following major surgery. We recommend that patients with known hypothyroidism who are scheduled for major surgery should be tested for thyroid function status and assessed for postoperative risk of hypothyroidism. Those who develop complications following major surgery, should be immediately tested for thyroid function to rule out myxedema coma.

Prolonged coma resulting from massive levothyroxine overdose and the utility of N-terminal prohormone brain natriuretic peptide (NT-proBNP).

INTRODUCTION: Levothyroxine overdose rarely results in systemic toxicity. We report a case of intentional levothyroxine overdose with a delayed onset coma and delirium lasting two weeks. CASE SUMMARY: A 72-year-old female ingested 12 mg levothyroxine. Initially, she was drowsy but quickly recovered and was well for the following two days. On day-3 post-overdose her mental state gradually deteriorated. She presented to the hospital with agitation, confusion and dyspnoea. Initial vital signs: P128 bpm, BP132/67 mmHg, temperature 38 °C and SpO2 97%RA. Features suggesting thyroid storm were present: fever >38 °C, tachycardia and persistent coma. Serum T4 and T3 were >150 pmol/L (normal: 8-16) and >30.8 pmol/L (normal: 3.2-6.1), respectively. These remained elevated for 11 days. She was treated with propranolol, propylthiouracil and cholestyramine. She remained intubated for two weeks without sedation. Her conscious state improved on day-13, coinciding with normalisation of serum T4. Normal cognition was regained four days later. N-terminal pro-brain natriuretic peptide (NT ProBNP) concentration was increased during coma and peaked 2 days prior to Glasgow Coma Score improving. DISCUSSION: Our case demonstrates features of thyrotoxicosis and thyroid storm with coma after massive levothyroxine overdose. Coma was associated with an increase in NT-proBNP concentration. This may be a potential marker for brain injury and recovery.

Diagnostic Accuracy of Procalcitonin for Early Aspiration Pneumonia in Critically Ill Patients with Coma: A Prospective Study.

BACKGROUND: Early diagnostic orientation for differentiating pneumonia from pneumonitis at the early stage after aspiration would be valuable to avoid unnecessary antibiotic therapy. We assessed the accuracy of procalcitonin (PCT) in diagnosing aspiration pneumonia (AP) in intensive care unit (ICU) patients requiring mechanical ventilation after out-of-hospital coma. METHODS: Prospective observational 2-year cohort study in a medical-surgical ICU. PCT, C-reactive protein (CRP) and white blood cell count (WBC) were measured at admission (H0) and 6 h (H), H12, H24, H48, H96, and H120 after inclusion. Lower respiratory tract microbiological investigations performed routinely in patients with aspiration syndrome were the reference standard for diagnosing AP. Performance of PCT, CRP, and WBC up to H48 in diagnosing AP was compared based on the areas under the ROC curves (AUC) and likelihood ratios (LR+ and LR-) computed for the best cutoff values. RESULTS: Of 103 patients with coma, 45 (44%) had AP. Repeated PCT assays demonstrated a significant increase in patients with AP versus without AP from H0 to H120. Among the three biomarkers, PCT showed the earliest change. ROC-AUC values were poor for all three biomarkers. Best ROC-AUC values for diagnosing AP were for CRP at H24 [0.73 (95%CI 0.61-0.84)] and PCT at H48 [0.73 (95%CI 0.61-0.84)]. LR+ was best for PCT at H24 (3.5) and LR- for CRP and WBC at H24 (0.4 and 0.4, respectively). CONCLUSIONS: Early and repeated assays of PCT, CRP, and WBC demonstrated significant increases in all three biomarkers in patients with versus without AP. All three biomarkers had poor diagnostic performance for ruling out AP. Whereas PCT had the fastest kinetics, PCT assays within 48 h after ICU admission do not help to diagnose AP in ICU patients with coma.

The neuron specific enolase (NSE) ratio offers benefits over absolute value thresholds in post-cardiac arrest coma prognosis.

INTRODUCTION: Serum neuron-specific enolase (NSE) levels have been shown to correlate with neurologic outcome in comatose survivors of cardiac arrest but use of absolute NSE thresholds is limited. This study describes and evaluates a novel approach to analyzing NSE, the NSE ratio, and evaluates the prognostic utility of NSE absolute value thresholds and trends over time. METHODS: 100 consecutive adult comatose cardiac arrest survivors were prospectively enrolled. NSE levels were assessed at 24, 48, and 72 h post-arrest. Primary outcome was the Glasgow Outcome Score (GOS) at 6 months post-arrest; good outcome was defined as GOS 3-5. Absolute and relative NSE values (i.e. the NSE ratio), peak values, and the trend in NSE over 72 h were analyzed. RESULTS: 98 patients were included. 42 (43%) had a good outcome. Five good outcome patients had peak NSE >33 µg/L (34.9-46.4 µg/L). NSE trends between 24 and 48 h differed between outcome groups (decrease by 3.0 µg/L (0.9-7.0 µg/L) vs. increase by 13.4 µg/L (-3.7 to 69.4 µg/L), good vs. poor, p = 0.004). The 48:24 h NSE ratio differed between the good and poor outcome groups (0.8 (0.6-0.9) vs. 1.4 (0.8-2.5), p = 0.001), and a 48:24 h ratio of ≥1.7 was 100% specific for poor outcome. CONCLUSIONS: The NSE ratio is a unique method to quantify NSE changes over time. Values greater than 1.0 indicate increasing NSE and may be reflective of ongoing neuronal injury. The NSE ratio obviates the need for an absolute value cut-off.

Clinical and Biological Predictors of Plasma Levels of Soluble RAGE in Critically Ill Patients: Secondary Analysis of a Prospective Multicenter Observational Study.

RATIONALE: Although soluble forms of the receptor for advanced glycation end products (RAGE) have been recently proposed as biomarkers in multiple acute or chronic diseases, few studies evaluated the influence of usual clinical and biological parameters, or of patient characteristics and comorbidities, on circulating levels of soluble RAGE in the intensive care unit (ICU) setting. OBJECTIVES: To determine, among clinical and biological parameters that are usually recorded upon ICU admission, which variables, if any, could be associated with plasma levels of soluble RAGE. METHODS: Data for this ancillary study were prospectively obtained from adult patients with at least one ARDS risk factor upon ICU admission enrolled in a large multicenter observational study. At ICU admission, plasma levels of total soluble RAGE (sRAGE) and endogenous secretory (es)RAGE were measured by duplicate ELISA and baseline patient characteristics, comorbidities, and usual clinical and biological indices were recorded. After univariate analyses, significant variables were used in multivariate, multidimensional analyses. MEASUREMENTS AND MAIN RESULTS: 294 patients were included in this ancillary study, among whom 62% were admitted for medical reasons, including septic shock (11%), coma (11%), and pneumonia (6%). Although some variables were associated with plasma levels of RAGE soluble forms in univariate analysis, multidimensional analyses showed no significant association between admission parameters and baseline plasma sRAGE or esRAGE. CONCLUSIONS: We found no obvious association between circulating levels of soluble RAGE and clinical and biological indices that are usually recorded upon ICU admission. This trial is registered with NCT02070536.

Serum levels of Selenium and C-reactive protein in comatose patients with severe traumatic brain injury during the first week of hospitalization: case-control study.

INTRODUCTION: Mortality and morbidity related to traumatic brain injuries still remain high in patients. Many authors reported the importance of Selenium in maintaining the integrity of brain functions. This fact is supported by clinical evidence that therapy with selenium supplementation could help patients suffering from brain disorders like neurodegenerative diseases. The aim of our study was to assess the relationship between Selenium concentration in serum and evolution of comatose patients with severe traumatic brain injury, in the first week of admission, and the correlation between selenium and C-reactive protein. METHODS: This case-control study was conducted with 64 comatose patients with TBI, in the Department of Anesthesiology and Reanimation, IbnSina University Hospital and Hospital of specialties in Rabat-Morocco, and healthy volunteers recruited in Blood transfusion center of Rabat. Blood sampling was collected from TBI patients, in the first week (3h after admission and each 48h during one week), and from healthy volunteers one time. Concentration of Se in serum was determined by electrochemical atomic absorption spectrometry. Statistical analysis was performed using Statistical software (SPSS) and the cases and controls were compared using the Mann-Whitney U test. A P-value < 0.05 was considered to be statistically significant. RESULTS: Comparison selenium concentration in the first day (D0), third day (D2) and fifth day according to the death and survival statue in patients did not show statistical significance (p > 0.05). Selenium concentration of D0 in patients and Selenium concentration in control group also did not show statistical significance (p > 0.05). Similarly, we did not report a correlation between selenium and C-reactive protein. CONCLUSION: According to our data selenium and CRP may not play a role in progression of coma state in patients with severe traumatic brain injury.

Complement cascade on severe traumatic brain injury patients at the chronic unconscious stage: implication for pathogenesis.

BACKGROUND: Patients who awake from severely traumatic brain injury (TBI) may remain unconscious for many years. Although behavioral assessment and functional imaging are currently used as diagnostic tools, the molecular basis underlying chronic condition has yet to be explored. METHOD: Plasma samples were obtained at 3 time points (1, 3 and 6 months) from 18 patients with chronic disorders of consciousness who survived severe TBI, and 6 healthy volunteers. A coupled isobaric tag for relative and absolute quantitation (iTRAQ)-based proteomics approach was used to screen differentially expressed proteins (DEPs) between patients and controls. Potential molecular mechanisms were further discussed through bioinformatics analyses. RESULT: In total, 300 plasma proteins <1% false discovery rates were identified and 32 proteins were consistently altered between patients and controls. Biological pathway analysis revealed that the DEPs were predominantly involved in complement cascade. CONCLUSIONS: This study discussed potential mechanisms of complement cascade underlying chronic stage in severe TBI.

Characteristics of jugular bulb oxygen saturation in patients after cardiac arrest: A prospective study.

BACKGROUND: Using cerebral oxygen venous saturation post-cardiac arrest (CA) is limited because of a small sample size and prior to establishment of target temperature management (TTM). We aimed to describe variations in jugular bulb oxygen saturation during intensive care in relation to neurological outcome at 6 months post- CA in cases where TTM 33°C was applied. METHOD: Prospective observational study in patients over 18 years, comatose immediately after resuscitation from CA. Patients were treated with TTM 33°C M and received a jugular bulb catheter within the first 26 hours post-CA. Neurological outcome was assessed at 6 months using the Cerebral Performance Categories (CPC) and dichotomized into good (CPC 1-2) and poor outcome (CPC 3-5). RESULTS: Seventy-five patients were included and 37 (49%) patients survived with a good outcome at 6 months post-CA. No differences were found between patients with good outcome and poor outcome in jugular bulb oxygen saturation. Higher values were seen in differences in oxygen content between central venous oxygen saturation and jugular bulb oxygen saturation in patients with good outcome compared to patients with poor outcome at 6 hours (12 [8-21] vs 5 [-0.3 to 11]% P = .001) post-CA. Oxygen extraction fraction from the brain illustrated lower values in patients with poor outcome compared to patients with good outcome at 96 hours (14 [9-23] vs 31 [25-34]% P = .008). CONCLUSIONS: Oxygen delivery and extraction differed in patients with a good outcome compared to those with a poor outcome at single time points. Based on the present findings, the usefulness of jugular bulb oxygen saturation for prognostic purposes is uncertain in patients treated with TTM 33°C post-CA.