S-100beta protein-serum levels in healthy children and its association with outcome in pediatric traumatic brain injury

OBJECTIVE: To describe normal serum levels of S-100beta in healthy children and determine whether serum S-100beta levels after traumatic brain injury are associated with outcome. DESIGN: Prospective cohort study. SETTING: Urban, tertiary care, children's teaching hospital. PATIENTS: A total of 136 healthy children and 27 children with traumatic brain injury. METHODS: Serum S-100beta levels were measured in 136 healthy children. A total of 27 children with traumatic brain injury had S-100beta levels collected within 12 hrs of injury. Other indices of severity of injury measured were admission Glasgow Coma Scale score, and Pediatric Risk of Mortality score at 24 hrs (PRISM 24). Outcome was measured by the Pediatric Cerebral Performance Category (PCPC) score at hospital discharge and 6 months postinjury or at death. MEASUREMENTS AND MAIN RESULTS: S-100beta levels in healthy children had a mean of 0.3 microg/L (90% confidence interval, 0.03-1.47) and inversely correlated with age, (r = -.32, p <.001). In children with traumatic brain injury, 6-month postinjury outcome inversely correlated with Glasgow Coma Scale score (r = -.47, p =.01) and correlated with PRISM 24 score (r =.83, p <.001) and S-100beta levels (r =.75, p <.001). Six months postinjury, comparing good outcome (PCPC < or = 3, n = 20) vs. poor outcome (PCPC > or = 4, n = 7), median admission Glasgow Coma Scale scores were 8 (range, 3-15) and 3 (range, 3-7, p =.01), median PRISM 24 scores were 7 (range, 0-19) and 30 (range, 18-35, p <.001), and median S-100beta levels were 0.85 microg/L (range, 0.08-4.8 microg/L) and 3.6 microg/L (range, 1.4-20 microg/L, p <.001), respectively. A serum S-100beta level of > or =2.0 microg/L is associated with poor outcome, with a sensitivity of 86% and a specificity of 95%. The area under the receiver operating curve for S-100beta was 0.94 (+/-0.05). CONCLUSIONS: Serum S-100beta levels in healthy children have a moderate inverse correlation with age. After traumatic brain injury in children, the acute assessment of serum S-100beta levels seems to be associated with outcome.     

神经元特异性烯醇化酶及脑活性肽100β蛋白在急性一氧化碳中毒中的意义

目的 探讨神经元特异性烯醇化酶(NSE)及脑活性肽100β(S-100β)蛋白在急性一氧化碳中毒(ACOP)患者中的临床意义。方法 将ACOP患者按格拉斯哥昏迷评分(GCS)分为轻度中毒组、中度中毒组、重度中毒组;选择健康体检者为对照组,采用化学发光免疫分析法测定所有研究对象血清NSE及S-100β蛋白水平。结果 与对照组比较,ACOP患者NSE及S-100β蛋白水平明显升高,两者比较差异有统计学意义(P<0.01);重度中毒组、中度中毒组患者NSE及S-100β蛋白水平高于轻度中毒组,3组比较差异有统计学意义(P<0.01);4例死亡患者NSE及S-100β蛋白水平显著升高,因病例数太少,未纳入统计分析。结论 NSE及S-100β蛋白可反映ACOP患者的脑损伤程度,对指导临床诊疗及判断预后有重要应用意义。     

The impact of the severity of sepsis on the risk of hypoglycaemia and glycaemic variability

Introduction

The purpose of this study was to assess the relation between glycaemic control and the severity of sepsis in a cohort of patients treated with intensive insulin therapy (IIT).

Methods

In a prospective, observational study, all patients in the intensive care unit (ICU) (n = 191) with sepsis, severe sepsis or septic shock were treated with IIT (target blood glucose (BG) level 80 to 140 mg/dl instead of strict normoglycaemia). BG values were analysed by calculating mean values, rate of BG values within different ranges, rate of patients experiencing BG values within different levels and standard deviation (SD) of BG values as an index of glycaemic variability.

Results

The number of patients with hypoglycaemia and hyperglycaemia was highly dependent on the severity of sepsis (critical hypoglycaemia ≤ 40 mg/dl: sepsis: 2.1%, severe sepsis: 6.0%, septic shock: 11.5%, p = 0.1497; hyperglycaemia: >140 mg/dl: sepsis: 76.6%, severe sepsis: 88.0%, septic shock: 100%, p = 0.0006; >179 mg/dl: sepsis: 55.3%, severe sepsis: 73.5%, septic shock: 88.5%, p = 0.0005; >240 mg/dl: sepsis: 17.0%, severe sepsis: 48.2%, septic shock: 45.9%, p = 0.0011). Multivariate analyses showed a significant association of SD levels with critical hypoglycaemia especially for patients in septic shock (p = 0.0197). In addition, SD levels above 20 mg/dl were associated with a significantly higher mortality rate relative to those with SD levels below 20 mg/dl (24% versus 2.5%, p = 0.0195).

Conclusions

Patients with severe sepsis and septic shock who were given IIT had a high risk of hypoglycaemia and hyperglycaemia. Among these patients even with a higher target BG level, IIT mandates an increased awareness of the occurrence of critical hypoglycaemia, which is related to the severity of the septic episode.     

Serum levels of the brain-derived proteins S-100 and NSE predict long-term outcome after cardiac arrest

Background and purpose: patients with cardiac arrest have a high mortality and the long-term outcome is doubtful. The prognosis is mainly dependent on clinical parameters. S-100 and neurone specific enolase (NSE) are established biochemical markers of central nervous system (CNS) injury. The purpose of this study was to validate the use of serum determinations of S-100 and NSE with neurological investigations in regard to brain damage and long-term outcome after cardiac arrest. Methods: neurological examinations were performed on 66 patients after cardiac arrest. Serum levels of S-100 and NSE were determined during the first 3 days of post arrest, using commercial luminescent immunoassays (LIAs). The main outcome variable was the Glasgow Outcome Scale (GOS), while secondary variables were the activity of daily living (ADL) index and mini mental state examination (MMSE). Outcome was determined at 1 year. Results: the serum levels of S-100 and NSE were increased during the first 3 days after the arrest and were related to coma depth, time of anoxia and abnormal brain stem reflexes. High levels predicted a poor outcome, according to the GOS (death, vegetative state and severe disability). The prognostic value of the brain damage markers was comparable with that of traditional clinical parameters. None of the secondary outcome variables (ADL and MMSE) was strongly associated with S-100 or NSE. Discussion: the serum levels of S-100 and NSE increased after cardiac arrest due to the anoxic brain damage. The determination of S-100 and NSE can be used as an adjunct to predict long-term outcome after cardiac arrest.     

Brain natriuretic peptide: A marker of myocardial dysfunction and prognosis during severe sepsis

OBJECTIVE: To investigate the value of brain natriuretic peptide plasma levels as a marker of systolic myocardial dysfunction during severe sepsis and septic shock. DESIGN: Prospective observational study. SETTING: Intensive care unit. PATIENTS: A total of 34 consecutive patients with severe sepsis (nine patients) or septic shock (25 patients) without previous cardiac, respiratory, or chronic renal failure. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Myocardial systolic performance was assessed by fractional area contraction (FAC) using echocardiography performed on days 2 (FACD2) and 8. Plasma levels of brain natriuretic peptide were measured at days 1-4 and 8 after the beginning of severe sepsis. Among 34 patients (Simplified Acute Physiology Score II, 43 +/- 2.5), 15 (44%) presented with initial myocardial dysfunction (FACD2 < 50%). Lungs were the origin of sepsis in 65% of patients. The 28-day mortality was 29%. Comparisons were performed between patients with (FACD2 < 50%) and without (FACD2 > or = 50%) myocardial dysfunction. Plasma levels of brain natriuretic peptide were significantly higher in patients with FACD2 < 50% than in those with FACD2 > or = 50% (p <.05) from day 2 to day 4. Brain natriuretic peptide levels were also significantly higher on days 2 and 3 in patients who died during their intensive care unit stay (p <.05). CONCLUSIONS: Systolic myocardial dysfunction is present in 44% of patient with severe sepsis or septic shock. In this setting, brain natriuretic peptide seems useful to detect myocardial dysfunction, and high plasma levels appear to be associated with poor outcome of sepsis, but further studies are needed.     

Impaired subcortical and cortical sensory evoked potential pathways in septic patients

OBJECTIVE: Sensory evoked potential (SEP) peak latencies were recorded in order to evaluate the incidence and severity of septic encephalopathy, testing the hypothesis that the occurrence of septic encephalopathy is more frequent than generally assumed. DESIGN: Prospective cohort study. SETTING: Medical intensive care unit of a university hospital. PATIENTS: Sixty-eight critically ill patients were studied within 48 hrs after the development of severe sepsis (n = 41) or septic shock (n = 27). INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Septic encephalopathy was defined as prolongation of SEP peak latencies beyond the upper limit of the reference range of subcortical (N13-N20 interpeak latency) and cortical SEP pathways (N20-N70 interpeak latency), as well as asymmetry of peak latencies marked by the presence of subclinical cerebral focal signs. Subcortical SEP pathways were impaired in 34% and cortical SEP pathways in 84% of all patients. The prolongation of the cortical SEP pathway correlated with the Acute Physiology and Chronic Health Evaluation III score (r = 0.23; p <.0001). SEP peak latencies did not differ in patients with severe sepsis compared with those with septic shock. Subclinical cerebral focal signs were present in 24% of the subcortical SEP pathways and in 6% of the cortical SEP pathways. CONCLUSIONS: Septic encephalopathy occurs more frequently than generally assumed, and its severity is associated with the severity of illness. The impairment of subcortical and cortical SEP pathways was not different between patients with severe sepsis and those with septic shock.     

Predictors of outcome in severely head-injured children

OBJECTIVE: Determine variables in the acute care period associated with survival and pediatric intensive care unit (PICU) length of stay (LOS) for children with severe traumatic brain injury. DESIGN: Retrospective cohort. SETTING: Level 1 pediatric trauma center. PATIENTS: Children (0-17 yrs) admitted 1991 to 1995 with nonpenetrating traumatic brain injury and admission Glasgow Coma Scale score of or=14. Predictors of outcome were abstracted, including Pediatric Trauma Score, Glasgow Coma Scale score, Pediatric Risk of Mortality, physiologic variables, computed tomography evidence of brain injury, and neuroresuscitative medications. The fatality rate was 24%. Age and gender were similar between groups (p >or= .1). Survival was independently predicted by 6-hr Glasgow Coma Scale score (odds ratio [OR] 4.6; 95% confidence interval [CI] 2.06-11.9; p < .001) and maximum systolic blood pressure (OR 1.05; 95% CI 1.01-1.09; p < .02). Odds of survival increased 19-fold when maximum systolic blood pressure was >or=135 mm Hg (OR 18.8; 95% CI 2.0-178.0; p < .01). By discharge, 67% of patients had an age-appropriate Glasgow Coma Scale score. Median hospital costs were 8,798 dollars for survivors: only mannitol use independently predicted high cost (odds ratio 4.9; 95% CI 1.2-19.1; p < .01). For survivors, median PICU LOS was 2 days, although 25% had LOS >6 days. Six-hour Glasgow Coma Scale score (OR 0.62; 95% CI 0.48-0.80; p < .001) and mannitol (OR 7.9; 95% CI 2.3-27.3; p < .001) were each independently associated with a prolonged LOS among survivors. CONCLUSIONS: Patients with higher 6-hr Glasgow Coma Scale scores were more likely to survive. Adjusting for severity of injury, survival was associated with maximum systolic blood pressure >or=135 mm Hg, suggesting that supranormal blood pressures are associated with improved outcome. Mannitol administration was associated with prolonged LOS, yet conferred no survival advantage. We suggest reevaluation of blood pressure targets and mannitol use in children with severe traumatic brain injury.     

Increased adenosine in cerebrospinal fluid after severe traumatic brain injury in infants and children: association with severity of injury and excitotoxicity.

OBJECTIVES: To measure adenosine concentration in the cerebrospinal fluid of infants and children after severe traumatic brain injury and to evaluate the contribution of patient age, Glasgow Coma Scale score, mechanism of injury, Glasgow Outcome Score, and time after injury to cerebrospinal fluid adenosine concentrations. To evaluate the relationship between cerebrospinal fluid adenosine and glutamate concentrations in this population. DESIGN: Prospective survey. SETTING: Pediatric intensive care unit in a university-based children's hospital. PATIENTS: Twenty-seven critically ill infants and children who had severe traumatic brain injury (Glasgow Coma Scale < 8), who required placement of an intraventricular catheter and drainage of cerebrospinal fluid as part of their neurointensive care. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Patients ranged in age from 2 months to 14 yrs. Cerebrospinal fluid samples (n = 304) were collected from 27 patients during the first 7 days after traumatic brain injury. Control cerebrospinal fluid samples were obtained from lumbar puncture on 21 infants and children without traumatic brain injury or meningitis. Adenosine concentration was measured by using high-pressure liquid chromatography. Adenosine concentration was increased markedly in cerebrospinal fluid of children after traumatic brain injury vs. controls (p < .001). The increase in cerebrospinal fluid adenosine was independently associated with Glasgow Coma Scale < or = 4 vs. > 4 and time after injury (both p < .005). Cerebrospinal fluid adenosine concentration was not independently associated with either age (< or = 4 vs. > 4 yrs), mechanism of injury (abuse vs. other), or Glasgow Outcome Score (good/moderately disabled vs. severely disabled, vegetative, or dead). Of the 27 patients studied, 18 had cerebrospinal fluid glutamate concentration previously quantified by high-pressure liquid chromatography. There was a strong association between increases in cerebrospinal fluid adenosine and glutamate concentrations (p < .005) after injury. CONCLUSIONS: Cerebrospinal fluid adenosine concentration is increased in a time- and severity-dependent manner in infants and children after severe head injury. The association between cerebrospinal fluid adenosine and glutamate concentrations may reflect an endogenous attempt at neuroprotection against excitotoxicity after severe traumatic brain injury.     

Outcome after cardiac arrest: predictive values and limitations of the neuroproteins neuron-specific enolase and protein S-100 and the Glasgow Coma Scale

BACKGROUND AND PURPOSE: Patients resuscitated from cardiac arrest are at risk of subsequent death or poor neurological outcome up to a persistent vegetative state. We investigated the prognostic value of several epidemiological and clinical markers and two neuroproteins, neuron-specific enolase (NSE) and S-100 protein (S-100), in 97 patients undergoing cardiopulmonary resuscitation (CPR) after non-traumatic cardiac arrest between 1998 and 2002. RESULTS: 52.6% of the patients died, 28.8% survived with severe, moderate or without neurological disorders, and 18.6% remained in a persistent vegetative state. Unconsciousness>48 h after CPR predicted a 60.6-fold (95% CI 14.3287-257.205, p=0.001) and a Glasgow Coma Scale (GCS)<6 points after 72 h a 11.2-fold (CI 95%, 3.55-36.44, p<0.001) risk of poor neurological outcome. Serum levels>or=65 ng/ml for NSE and >or=1.5 microg/l for S-100 increased the risk of death and persistent vegetative state 16.8 (95% CI 2.146-131.520)- and 12.6 (95% CI 1.1093-99.210)-fold, respectively. By combination of the GCS with elevated serum concentrations of both neuroproteins above the cut off levels on third day after CPR a poor neurological outcome was predicted with a specificity of 100%. CONCLUSION: The combination of GCS with the serum levels of both neuroproteins at 72 h after CPR permit a more reliable prediction of outcome in post arrest coma than the single markers alone, independent of the application of anaesthetic agents.     

Immediate S-100B and neuron-specific enolase plasma measurements for rapid evaluation of primary brain damage in alcohol-intoxicated,minor head-injured patients

The neuroproteins S-100B and neuron-specific enolase (NSE) released into the circulation are suggested to be reliable markers for primary brain damage. However, safe identification of relevant post-traumatic complications after minor head injury (MHI) is often hampered by acute intoxication of the patients. The objective of this study was to determine the diagnostic validity of immediate plasma measurements of S-100B and NSE in comparison with neurological examinations and cerebral computed tomography (CCT) findings in alcohol-intoxicated MHI patients. One hundered thrity-nine MHI individuals were enrolled in this prospective study during Munich's Oktoberfest 2000. Plasma levels of S-100B and NSE as well as serum alcohol and glucose values were determined by fully automated assays immediately after admission. The results were compared with Glasgow Coma Scale score, a brief neurological examination, and the CCT findings. Without being influenced by alcohol, median S-100B levels of the CCT+ group were significantly increased compared with those of the CCT- group (P < 0.001). NSE, alcohol, and glucose levels showed no significant group differences. As calculated by the ROC analysis, a cutoff value of 0.21 ng/mL with an area under the curve of 0.864 clearly differentiates between CCT+ and CCT- patients at a sensitivity of 100%, a specificity of 50.0%, and a positive likelihood ratio of 2.0. Although acute alcohol intoxication did not confound plasma measurements of S-100B and NSE, only S-100B levels below the cutoff level of 0.21 ng/mL seem to indicate absence of primary brain damage. Thus, in addition to routine neurological examinations, S-100B measurements immediately after admission might help to reduce CCT scans in alcohol-intoxicated patients early after MHI.     

Effect of stress doses of hydrocortisone on S-100B vs. interleukin-8 and polymorphonuclear elastase levels in human septic shock.

Stress doses of hydrocortisone are known to have immunomodulatory effects in patients with hyperdynamic septic shock. The prognosis correlates with the presence and severity of septic encephalopathy. However, neurological evaluation is influenced by the use of analgesia sedation during artificial ventilation. The objective of this study was to demonstrate the effect of stress doses of hydrocortisone during the initial phase of human septic shock on the serum values of the neurospecific protein S-100B in comparison to the inflammation markers interleukin (IL)-8 in serum and polymorphonuclear (PMN) elastase in plasma. A total of 24 consecutive patients, who met the American College of Chest Physicians/Society of Critical Care Medicine criteria for septic shock, were enrolled in this prospective, randomized, double-blind, single-center trial. The severity of illness at recruitment was graded using the Acute Physiology and Chronic Health Evaluation II and the Simplified Acute Physiology Score II scoring systems. Multi-organ dysfunction syndrome was described by the Sepsis-related Organ Failure Assessment (SOFA) score. All patients were prospectively randomized to receive either stress doses of hydrocortisone or placebo. Hydrocortisone was started in 12 patients with a loading dose of 100 mg and followed by a continuous infusion of 0.18 mg/kg/h for 6 days. Median S-100B serum levels of the hydrocortisone group decreased from 0.32 ng/mL at study entry to 0.07 ng/mL 6 days later without significant differences compared to the placebo group. Initial IL-8 serum levels were significantly higher in the hydrocortisone group up to 12 h after study entry, and significantly decreased from 715 to 17 pg/mL at the end of the observation period. Median PMN elastase plasma levels were not affected by hydrocortisone infusion. Patients with initial S-100B serum levels > 0.50 ng/mL revealed significantly higher SOFA scores up to 30 h, IL-8 serum levels up to 12 h, and PMN elastase plasma levels up to 36 h after study entry than those patients with < or = 0.50 ng/mL. These effects were independent of the amount of fluid correction for hemodilution. Starting S-100B, IL-8 and PMN elastase values of the hydrocortisone group were within the ranges already known in patients with out-of-hospital cardiac arrest or severe traumatic brain injury. Stress doses of hydrocortisone resulted in a significant reduction in IL-8 serum, but not in S-100B serum and PMN elastase plasma concentrations in patients with hyperdynamic septic shock. For the first time, a similar extent of S-100B increase in serum of septic patients at the time of diagnosis was shown as reported for cardiac arrest or severe traumatic brain injury.     

The early fall in levels of S-100 beta in traumatic brain injury.

Protein S-100 beta has been suggested as a prognostic marker in traumatic brain injury. However, little is known of its behaviour in the immediate post-injury period. With Ethics Committee approval, we recruited 30 patients with a history of head injury presenting to our Accident and Emergency Department. Blood was taken on arrival and at four hours post-injury. Serum S-100 beta was estimated using an immunoluminometric assay. Levels of S-100 beta were seen to fall rapidly with time. Half-time was distributed non-parametrically with a median of 198 minutes. Using the Mann-Whitney U test we found a statistically significant difference between non-desirable (Glasgow Outcome Score 1-3) and desirable (Glasgow Outcome Score 4-5) outcome on admission (p = 0.0155) but not at four hours (p = 0.1336). Levels of S-100 beta fell rapidly after its release following traumatic brain injury. Time after injury is therefore critical in assessing the significance of levels of S-100 beta, and sampling should be as early as possible to gain maximum information. If S-100 beta is to be assessed as a monitor of ongoing brain injury in the intensive therapy unit sampling must be frequent (e.g. every 4 hours) to be able to detect rises in serum levels before they have decayed to baseline.     

Pronounced elevation of resistin correlates with severity of disease in severe sepsis and septic shock

OBJECTIVE: Resistin induces insulin resistance in mice. In humans, recent data suggest that resistin functions as a proinflammatory cytokine. Here, we studied resistin up to 2 wks after admission in patients with septic shock and/or severe sepsis. DESIGN: Two prospective studies of patients with sepsis and in vitro studies of resistin interaction with monocytes. SETTING: Intensive care unit at Karolinska University Hospital and Center for Infectious Medicine, Karolinska Institute, Huddinge, Sweden. PATIENTS: Twenty-nine patients with severe sepsis and 66 with septic shock. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Ninety-five patients were studied, 25 of whom died within 28 days. Resistin and cytokine levels and routine biochemistry were measured at three to six defined time points during the first 2 wks after admission and were correlated to other cytokines, glucose levels, body mass index, Acute Physiology and Chronic Health Evaluation II, and Sepsis-related Organ Failure Assessment scores.Serum resistin was significantly elevated compared with healthy controls (p < .000001) and correlated with severity of disease as measured by Acute Physiology and Chronic Health Evaluation II and Sepsis-related Organ Failure Assessment scores, with an increasingly strong degree of correlation over time. Median levels were four- to eight-fold higher than controls and remained high up to 2 wks after admission to the intensive care unit. Levels correlated with interleukin-6, interleukin-8, interleukin-10, tumor necrosis factor-alpha, creatinine, D-dimer, and lactate, but not with p-glucose or body mass index. In vitro, resistin was released from monocytes after stimulation with either lipopolysaccharide or high mobility group box 1 protein. Recombinant resistin itself up-regulated intercellular adhesion molecule-1 on monocytes. CONCLUSIONS: This is the first study assessing systemic levels of resistin in patients with septic shock/severe sepsis. We show that resistin is a marker of severity of disease and possibly a mediator of the prolonged inflammatory state seen in infected critically ill patients. Further exploration of resistin as a therapeutic target and marker of disease is merited.     

Sepsis severity is the major determinant of circulating thrombopoietin levels in septic patients

OBJECTIVE: To measure serum thrombopoietin levels and to investigate their relationship with platelet counts and other potential determinants in septic patients. DESIGN: Prospective study comparing septic patients and healthy volunteers. SETTING: General intensive care units in two tertiary university hospitals. PATIENTS: A total of 152 consecutive septic patients (69 with sepsis, 24 with severe sepsis, and 59 with septic shock). Twenty-two healthy volunteers served as control subjects. Sepsis severity was determined by grading septic patients in those having sepsis, severe sepsis, and septic shock. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: After blood sampling, platelet counts, and serum thrombopoietin, interleukin-6 and C-reactive protein levels were measured. Platelets did not decrease in patients with sepsis, but they significantly decreased in patients with severe sepsis and septic shock (p <.01 vs. controls and sepsis). In contrast, thrombopoietin levels (median [range]) increased in patients with sepsis (159 [34-1272] pg/mL) compared with controls (57 [33-333] pg/mL, p <.001), exhibiting further significant increase in patients with severe sepsis and septic shock (461 [73-1550] and 522 [45-2313] pg/mL, respectively, p <.001 vs. sepsis). In multiple regression analysis, thrombopoietin levels were independently related only to sepsis severity (higher in patients with increased sepsis severity, p <.001) and platelet counts (higher in patients with lower platelet counts, p =.004). Sepsis severity accounted for most of the variance explained by the model. Thrombopoietin was significantly related to interleukin-6 (r =.26) and C-reactive protein (r =.37, p <.001 for both). In serial measurements, interleukin-6 peak values constantly preceded those of thrombopoietin, whereas peaks in thrombopoietin levels coincided with clinical episodes of septic shock. CONCLUSIONS: Sepsis severity is the major determinant of elevated thrombopoietin levels in septic patients, whereas platelet count is a secondary determinant. Thrombopoietin represents a potential marker of sepsis severity.     

Predictive value of N-terminal pro-brain natriuretic peptide in severe sepsis and septic shock

OBJECTIVE: The aim of this study was to evaluate the predictive value of N-terminal pro-brain natriuretic peptide (NT-proBNP) on mortality in a large, unselected patient population with severe sepsis and septic shock. DESIGN AND SETTING: Prospective observational cohort study about incidence and prognosis of sepsis in 24 intensive care units in Finland (the FINNSEPSIS study). PATIENTS: A total of 254 patients with severe sepsis or septic shock. MEASUREMENTS: After informed consent, the blood tests for NT-proBNP analyses were drawn on the day of admission and 72 hrs thereafter. Patients' demographic data were collected, and intensive care unit and hospital mortality and basic hemodynamic and laboratory data were recorded daily. MAIN RESULTS: NT-proBNP levels at admission were significantly higher in hospital nonsurvivors (median, 7908 pg/mL) compared with survivors (median, 3479 pg/mL; p = .002), and the difference remained after 72 hrs (p = .002). The receiver operating characteristic curves of admission and 72-hr NT-proBNP levels for hospital mortality resulted in area under the curve values of 0.631 (95% confidence interval, 0.549-0.712; p = .002) and 0.648 (95% confidence interval, 0.554-0.741; p = .002), respectively. In logistic regression analyses, NT-proBNP values at 72 hrs after inclusion and Simplified Acute Physiology Score for the first 24 hrs were independent predictors of hospital mortality. Pulmonary artery occlusion pressure (p < .001), plasma creatinine clearance (p = .001), platelet count (p = .03), and positive blood culture (p = .04) had an independent effect on first-day NT-proBNP values, whereas after 72 hrs, only plasma creatinine clearance (p < .001) was significant in linear regression analysis. CONCLUSION: NT-proBNP values are frequently increased in severe sepsis and septic shock. Values are significantly higher in nonsurvivors than survivors. NT-proBNP on day 3 in the intensive care unit is an independent prognostic marker of mortality in severe sepsis.     

Comparable increase of B-type natriuretic peptide and amino-terminal pro-B-type natriuretic peptide levels in patients with severe sepsis, septic shock, and acute heart failure

OBJECTIVE: B-type natriuretic peptide (BNP) and N-terminal pro-BNP measurements are used for the diagnosis of congestive heart failure (HF). However, the diagnostic value of these tests is unknown under septic conditions. We compared patients with severe sepsis or septic shock and patients with acute HF to unravel the influence of the underlying diagnosis on BNP and N-terminal pro-BNP levels. DESIGN: Prospective, clinical study. SETTING: Academic medical intensive care unit (ICU). PATIENTS: A total of 249 consecutive patients were screened for the diagnosis of sepsis or HF. Sepsis was defined according to published guidelines. HF was diagnosed in the presence of an underlying heart disease and congestive HF, pulmonary edema, or cardiogenic shock. INTERVENTIONS: BNP and N-terminal pro-BNP were measured from blood samples that were drawn daily for routine analysis. MEASUREMENTS AND MAIN RESULTS: We identified 24 patients with severe sepsis or septic shock and 51 patients with acute HF. At admission, the median (range) BNP and N-terminal pro-BNP levels were 572 (13-1,300) and 6,526 (198-70,000) ng/L in patients with sepsis and 581 (6-1,300) and 4,300 (126-70,000) ng/L in patients with HF. The natriuretic peptide levels increased during the ICU stay, but the differences between the groups were not significant. Nine patients with sepsis and eight patients with HF were monitored with a pulmonary artery catheter. Mean (sd) pulmonary artery occlusion pressure were 16 (4.2) and 22 (5.3) mm Hg (p = .02), and cardiac indexes were 4.6 (2.8) and 2.2 (0.6) L/min/m (p = .03) in patients with sepsis and HF, respectively. Despite these clear hemodynamic differences BNP and N-terminal pro-BNP levels were not statistically different between the two groups. CONCLUSION: In patients with severe sepsis or septic shock, BNP and N-terminal pro-BNP values are highly elevated and, despite significant hemodynamic differences, comparable with those found in acute HF patients. It remains to be determined how elevations of natriuretic peptide levels are linked to inflammation and sepsis-associated myocardial dysfunction.     

Long-latency auditory-evoked potentials in severe traumatic brain injury

OBJECTIVE: To detect the effects of different deviant stimuli on long-latency auditory-evoked potentials (LLAEPs) in patients with severe impairment of consciousness from traumatic brain injury (TBI) and to define their prognostic value for late functional outcome. DESIGN: Correlational study on a prospective cohort. SETTING: Brain injury rehabilitation center. PATIENTS: Eleven volunteers and 21 consecutively sampled patients with severe TBI referred to the inpatient intensive rehabilitation unit of primary care in a university-based system. MAIN OUTCOME MEASURES: The LLAEPs recorded with different paradigms; and the Glasgow Outcome Scale (GOS), Disability Rating Scale (DRS), FIMtrade mark instrument, and Neurobehavioural Rating Scale (NBHRS). RESULTS: N100-P150 complex showed high reliability. Patients with good outcomes showed N100 and P150 mean latencies similar to those of unimpaired patients and shorter than patients with unfavorable outcomes. When the deviant stimulus was the patient's name, N100 latency showed high correlations with DRS (p <.007), FIM (p <.01), and NBHRS (p <.009). P250 and P300 showed a low percentage of occurrence with passive paradigms in both patients and controls. Their scores were inversely correlated to the Glasgow Coma Scale (p <.03) and the Innsbruck Coma Scale (p <.003), but no significant correlations were found with functional and behavioral outcomes. Patients with GOS score 1-2 1 year posttrauma had significantly longer latency and lower amplitude of N100 and P150 than those with GOS score 4-5. CONCLUSIONS: LLAEPs can be recorded in patients with severe impairment of consciousness by means of passive paradigms. The use of a stimulus that is relevant for the patient can enhance the accuracy of the test and its relationship with functional outcome.     

Prognostic value of protein C concentrations in neutropenic patients at high risk of severe septic complications

OBJECTIVE: To assess the prognostic value of protein C, endogenous activated protein C, and D-dimer concentrations in patients at high risk of developing severe septic complications secondary to cytostatic chemotherapy. DESIGN: Prospective, comparative, single-center study. SETTING: Specialized ward for treating patients with acute leukemia and associated intensive care unit at a university hospital. SUBJECTS: Twenty-six consecutive patients who developed either severe sepsis (n = 13) or septic shock (n = 13) during chemotherapy-induced neutropenia (leukocytes <1,000/microL). INTERVENTION: None, other than standard care. MEASUREMENTS AND MAIN RESULTS: Baseline blood samples were obtained from 97 adult patients treated with intensive cytostatic chemotherapy. Serial blood sampling was performed in 62 of 97 patients who developed fever (>38.3 degrees C). Thirteen patients progressed to severe sepsis and 13 patients to septic shock. Protein C, endogenous activated protein C, and D-dimer were measured in these 26 patients. At fever onset, protein C concentrations decreased from normal baseline concentrations and were significantly lower in the group of patients who progressed to septic shock compared with those who developed severe sepsis (medians for protein C activity: 23.1% vs. 69.5%; p = .0003). The median elapsed time between detection of fever and the diagnosis of severe sepsis or septic shock was 16 hrs and 12 hrs, respectively. All septic shock patients died, whereas patients who progressed only to severe sepsis survived. CONCLUSIONS: Septic shock in neutropenic patients is associated with increased protein C consumption. The data demonstrate that the coagulation cascade is activated and produces a hypercoagulable state before the onset of clinical symptoms of severe sepsis and septic shock. Low protein C concentrations at the onset of fever and before the onset of clinical symptoms of severe sepsis or septic shock may have prognostic value in predicting an unfavorable outcome. Protein C measurements may help identify patients at risk in an early phase of neutropenic sepsis. It is also attractive to speculate that because low protein C concentrations were seen in these patients, protein C replacement may be beneficial in sepsis.     

Endocan, a new endothelial marker in human sepsis

OBJECTIVES: a) To evaluate in septic patients the blood levels of endocan, a circulating proteoglycan, which regulates leukocyte function-associated antigen-1/intercellular adhesion molecule-1 interactions in vitro; b) to determine whether endocan could be used as a diagnostic and prognostic marker in sepsis in the intensive care unit; and c) to study kinetics of endocan secretion by endothelial cells in vitro after stimulation by soluble mediators involved in sepsis. DESIGN: Prospective observational study. SETTING: Intensive care unit of the University Hospitals of Lille, France, and Geneva, Switzerland. PATIENTS: All patients admitted to the intensive care unit over a 6-month period with clinical evidence of severe sepsis or septic shock. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: In vitro, we showed a sustained endocan secretion by endothelial cells after stimulation by lipopolysaccharide and tumor necrosis factor-alpha. Circulating levels of endocan measured in 63 patients admitted to the intensive care unit with sepsis were significantly elevated compared with 20 healthy donors and seven patients with systemic inflammatory response syndrome: 2.71 +/- 4.88 ng/mL vs. 0.77 +/- 0.44 ng/mL vs. 0.68 +/- 1.03 ng/mL (median +/- interquartile range, p < .001). Endocan levels were higher in patients with septic shock (6.11 +/- 12.99 ng/mL, n = 22) than in patients with severe sepsis (1.97 +/- 7.8 ng/mL, n = 12) or sepsis (1.95 +/- 1.63 ng/mL, n = 29). Measurement of endocan at intensive care unit admission revealed higher levels in nonsurvivors (n = 12) than in patients still alive 10 days later (n = 51, 6.98 +/- 13.8 vs. 2.45 +/- 4.09, p < .01). CONCLUSIONS: These results suggest that in septic patients, endocan blood level is related to the severity of illness and the outcome of the patient and may represent a novel endothelial cell dysfunction marker.     

S-100β and neuron-specific enolase levels in carbon monoxide–related brain injury

Introduction

Carbon monoxide (CO) toxicity may cause persistent injuries in tissues sensitive to hypoxia. Neuropsychiatric sequelae may be observed in about 67% of cases after severe CO exposure.

Aim

The aims of this study were to demonstrate the usefulness of S-100β and neuron-specific enolase (NSE) in CO intoxications, show the degree of neurological response, and determine the indications for hyperbaric oxygen treatment (HBOT) as biochemical markers.

Results

The S-100β and NSE levels of the sera of 30 patients were studied upon admittance and at the third and sixth hours. S-100β levels were found to be high in all 3 analyses. There was no significant change in NSE levels. When the S-100β levels were compared with Glasgow Coma Scale levels, a strong negative correlation was found for all hours (r = −0.7, −0.8; P = .00). The correlation between S-100β and carboxyhemoglobin levels at the initial hour was found to be statistically significant (r = 0.4; P = .01). The S-100β levels in patients receiving HBOT showed a considerable decrease compared with those in patients not receiving the treatment. The same decrease was valid for NSE, although it was insignificant.

Conclusion

S-100β may be useful in evaluating intoxications as an early biochemical marker in CO intoxications, as well as in the differential diagnosis due to other causes, and in determining HBOT indications.