***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: Introduction The pathophysiology of sepsis-associated delirium is not completely understood and the data on cerebral perfusion in sepsis are conflicting . We tested the hypothesis that cerebral perfusion and selected serum markers of inflammation and delirium differ in septic patients with and without sepsis-associated delirium . Methods We investigated 23 adult patients with sepsis , severe sepsis , or septic shock with an extracranial focus of infection and no history of intracranial pathology . Patients were investigated after stabilisation within 48 hours after admission to the intensive care unit . Sepsis-associated delirium was diagnosed using the confusion assessment method for the intensive care unit .  Mean arterial pressure ( MAP ) , blood flow velocity ( FV ) in the middle cerebral artery using transcranial Doppler , and cerebral tissue oxygenation using near-infrared spectroscopy were monitored for 1 hour . An index of cerebrovascular autoregulation was calculated from MAP and FV data . C-reactive protein ( CRP ) , interleukin-6 ( IL-6 ) , S-100β , and cortisol were measured during each data acquisition . Results Data from 16 patients , of whom 12 had sepsis-associated delirium , were analysed . There were no significant correlations or associations between MAP , cerebral blood FV , or tissue oxygenation and sepsis-associated delirium . However , we found a significant association between sepsis-associated delirium and disturbed autoregulation ( P = 0.015 ) . IL-6 did not differ between patients with and without sepsis-associated delirium , but we found a significant association between elevated CRP ( P = 0.008 ) , S-100β ( P = 0.029 ) , and cortisol ( P = 0.011 ) and sepsis-associated delirium . Elevated CRP was significantly correlated with disturbed autoregulation ( Spearman rho = 0.62 , P = 0.010 ) . Conclusion In this small group of patients , cerebral perfusion assessed with transcranial Doppler and near-infrared spectroscopy did not differ between patients with and without sepsis-associated delirium . However , the state of autoregulation differed between the two groups . This may be due to inflammation impeding cerebrovascular endothelial function . Further investigations defining the role of S-100β and cortisol in the diagnosis of sepsis-associated delirium are warranted . Trial registration Clinical Trials.gov NCT00410111 Abstract . Objective : Perfusion abnormalities are an overall phenomenon in severe sepsis and septic shock , leading to organ dysfunction . We investigated whether  carbon dioxide  (CO2)-induced vasomotor reactivity ( VMR ) is impaired in septic patients , compared with values obtained outside sepsis . Design : Prospect i ve , clinical study . Setting : Six-bed neurologic critical care unit of a university hospital . Patients and participants : Eight consecutive patients with severe sepsis and septic shock . Measurements and results : CO2-reactivity was measured during and outside a period of severe sepsis or septic shock according to ACCP/SCCM criteria by means of transcranial Doppler sonography and near-infrared spectroscopy ( NIRS ) .  VMR was calculated as the percentage change of cerebral blood flow velocity ( normalized CO2-reactivity , NCR ) and absolute changes in concentration of oxygenated hemoglobin , deoxygenated hemoglobin , total hemoglobin ( HbO2 , Hb , HbT ) and Hbdiff ( difference between HbO2 and Hb ) in µmol/l per 1 % increase in end-tidal CO2 ( CR-HbO2 , CR-Hb , CR-HbT , CR-Hbdiff ) . NCR and NIRS-reactivities were significantly reduced during severe sepsis and septic shock compared with values outside sepsis ( mean , SD , Wilcoxon ) : NCR 11.0 ( 7.1 ) versus 30.7 ( 13.0 ) , p<0.02 ; CR-HbO2 0.70 ( 0.61 ) versus 2.33 ( 1.11 ) , p<0.02 ; CR-Hb –0.17 ( 0.74 ) versus –1.42 ( 1.28 ) , p<0.04 ; CR-HbT 0.53 ( 0.48 ) versus 1.05 ( 0.40 ) , p<0.03 ; CR-Hbdiff 0.91 ( 1.33 ) versus 3.75 ( 2.33 ) , p<0.02 . This indicates a severely disturbed VMR . Conclusions : In the advent of a disturbed cerebral autoregulation , critical drops in blood pressure during sepsis are transferred directly into the vascular bed , leading to cerebral hypoperfusion . This mechanism might contribute to the pathogenesis of septic encephalopathy Introduction Pathophysiology of brain dysfunction due to sepsis remains poorly understood . Cerebral microcirculatory alterations may play a role ; however , experimental data are scarce . This study sought to investigate whether the cerebral microcirculation is altered in a clinical ly relevant animal model of septic shock . Methods Fifteen anesthetized , invasively monitored , and mechanically ventilated female sheep were allocated to a sham procedure ( n = 5 ) or sepsis ( n = 10 ) , in which peritonitis was induced by intra-abdominal injection of autologous faeces . Animals were observed until spontaneous death or for a maximum of 20 hours . In addition to global hemodynamic assessment , the microcirculation of the cerebral cortex was evaluated using Sidestream Dark-Field ( SDF ) videomicroscopy at baseline , 6 hours , 12 hours and at shock onset . At least five images of 20 seconds each from separate areas were recorded at each time point and stored under a r and om number to be analyzed , using a semi-quantitative method , by an investigator blinded to time and condition . Results All septic animals developed a hyperdynamic state associated with organ dysfunction and , ultimately , septic shock . In the septic animals , there was a progressive decrease in cerebral total perfused vessel density ( from 5.9 ± 0.9 at baseline to 4.8 ± 0.7 n/mm at shock onset , P = 0.009 ) , functional capillary density ( from 2.8 ± 0.4 to 2.1 ± 0.7 n/mm , P = 0.049 ) , the proportion of small perfused vessels ( from 95 ± 3 to 85 ± 8 % , P = 0.02 ) , and the total number of perfused capillaries ( from 22.7 ± 2.7 to 17.5 ± 5.2 n/mm , P = 0.04 ) . There were no significant changes in microcirculatory flow index over time . In sham animals , the cerebral microcirculation was unaltered during the study period . Conclusions In this model of peritonitis , the cerebral microcirculation was impaired during sepsis , with a significant reduction in perfused small vessels at the onset of septic shock . These alterations may play a role in the pathogenesis of septic encephalopathy Introduction The pathophysiology of sepsis-associated encephalopathy ( SAE ) is not entirely clear . One of the possible underlying mechanisms is the alteration of the cerebral microvascular function induced by the systemic inflammation . The aim of the present work was to test whether cerebral vasomotor-reactivity is impaired in patients with SAE . Methods Patients fulfilling the criteria of clinical sepsis and showing disturbance of consciousness of any severity were included ( n = 14 ) . Non-septic persons whithout previous diseases affecting cerebral vasoreactivity served as controls ( n = 20 ) .  Transcranial Doppler blood flow velocities were measured at rest and at 5 , 10 , 15 and 20 minutes after intravenous administration of 15 mg/kgBW acetazolamide . The time course of the acetazolamide effect on cerebral blood flow velocity ( cerebrovascular reactivity , CVR ) and the maximal vasodilatory effect of acetazolemide ( cerebrovascular reserve capacity , CRC ) were compared among the groups . Results Absolute blood flow velocities after adminsitration of the vasodilator drug were higher among control subjects than in SAE . Assessment of the time-course of the vasomotor reaction showed that patients with SAE reacted slower to the vasodilatory stimulus than control persons . When assessing the maximal vasodilatory ability of the cerebral arterioles to acetazolamide during vasomotor testing , we found that patients with SAE reacted to a lesser extent to the drug than did control subjects ( CRC controls:46.2 ± 15.9 % , CRC SAE : 31,5 ± 15.8 % , P < 0.01 ) . Conclusions We conclude that cerebrovascular reactivity is impaired in patients with SAE . The clinical significance of this pathophysiological finding has to be assessed in further studies OBJECTIVE To determine whether the severity of septic encephalopathy is correlated with gram-negative bacteremia and mortality and whether there exists a single or combination of metabolic derangements(s ) that cause septic encephalopathy . DESIGN AND SETTING Prospect i ve case series in an academic medical center . PATIENTS Fifty patients selected according to clinical and laboratory criteria for severe sepsis . The criteria included temperature , heart rate , respiratory rate , and hypotension and /or signs of systemic hypoperfusion . MAIN OUTCOME MEASURES A single or combination of metabolic and laboratory derangements and organ failures , three different methods to grade the severity of septic encephalopathy , Acute Physiology and Chronic Health Evaluation II ( APACHE II ) scores , gram-negative bacteremia and infection , and mortality . RESULTS Encephalopathy was associated with an increase in mortality when grade d by the Glasgow Coma Score ; a score of 15 had 16 % mortality , 13 to 14 had 20 % , 9 to 12 had 50 % , and 3 to 8 had 63 % mortality ( P < .05 ) . Bacteremia was associated with encephalopathy ; 13 % of septic patients without encephalopathy vs 59 % of patients with encephalopathy had bacteremia ( P < .001 ) when grade d by altered mental status . Septic encephalopathic patients had elevated serum urea nitrogen and bilirubin levels , increased APACHE II scores , and a higher incidence of renal failure . CONCLUSIONS The severity of septic encephalopathy correlated with mortality , bacteremia , and renal and hepatic dysfunction . The Glasgow Coma Score is a useful tool for characterizing septic encephalopathy . Considerable variations can be found according to different criteria used to classify septic encephalopathy Objective To study the correlation between a dynamic index of cerebral autoregulation assessed with blood flow velocity ( FV ) using transcranial Doppler , and a tissue oxygenation index ( TOI ) recorded with near-infrared spectroscopy ( NIRS ) . Methods Twenty-three patients with sepsis , severe sepsis , or septic shock were monitored daily on up to four consecutive days .  FV , TOI , and mean arterial blood pressure ( ABP )  were recorded for 60 min every day . An index of autoregulation ( Mx ) was calculated as the moving correlation coefficient between 10-s averaged values of FV and ABP over moving 5 min time-windows . The index Tox was evaluated as the correlation coefficient between TOI and ABP in the same way . The indices Mx and Tox , ABP and arterial partial pressure of CO2 were averaged for each patient . Results Synchronized slow waves , presenting with periods from 20 s to 2 min , were seen in the TOI and FV of most patients , with a reasonable coherence between the signals in this b and width ( coherence > 0.5 ) . The indices , Mx and Tox , demonstrated good correlation with each other ( R = 0.81 ; P < 0.0001 ) in the whole group of patients . Both indices showed a significant ( P < 0.05 ) tendency to indicate weaker autoregulation in the state of vasodilatation associated with greater values of arterial partial pressure of CO2 or lower values of ABP . Conclusion NIRS shows promise for the continuous assessment of cerebral autoregulation in adults INTRODUCTION The pathophysiology of sepsis-associated encephalopathy ( SAE ) is not entirely clear , but one of the possible underlying mechanisms is the alteration of the cerebral microvascular function . The aim of the present work was to test whether cerebral vasomotor reactivity is impaired in patients with severe sepsis . METHODS Patients fulfilling the criteria of clinical sepsis and showing at least 2 organ dysfunctions were included ( n = 16 ) . Nonseptic healthy persons without previous diseases affecting cerebral vasoreactivity served as controls ( n = 16 ) .  Transcranial Doppler blood flow velocities were measured at rest and at 5 , 10 , 15 , and 20 minutes after intravenous administration of 15 mg/kg acetazolamide . The time course of the acetazolamide  effect on cerebral blood flow velocity ( cerebrovascular reactivity [ CVR ] ) and the 
    Output:
    
A temporal pattern of the evolution of the illness was found .
In early sepsis , the median blood flow velocity ( Vm ) and pulsatility index ( PI ) increased , and the cerebral autoregulation ( CA ) remained unchanged .
In contrast , Vm normalization , PI reduction and CA impairment were found in later sepsis ( patients with severe sepsis or septic shock ) .
Cerebral haemodynamic is impaired in sepsis .
Modifications in cerebral blood flow may be consequence to the endothelial dysfunction of the microvasculature induced by the release of inflammatory mediators .
A better underst and ing of cerebral hemodynamics may improve the clinical management of patients with sepsis and , consequently , improve clinical outcomes