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Introduction: Previous studies have found higher circulating levels of tissue inhibitor of matrix metalloproteinase (TIMP)-1 in nonsurviving septic patients than in surviving septic patients, and an association between the 372 T/C genetic polymorphism of TIMP-1 and the risk of developing certain diseases. However, the relationship between genetic polymorphisms of TIMP-1, circulating TIMP-1 levels and survival in patients with severe sepsis has not been examined, and this was the objective of the study. Methods: This multicentre, prospective, observational study was carried out in six Spanish ICUs. We determined the 372 T/C genetic polymorphism of TIMP-1 (rs4898), serum levels of TIMP-1, matrix metalloproteinase (MMP)-9, MMP-10, TNFa, IL-10 and plasma plasminogen activator inhibitor-1 (PAI-1). Survival at 30 days from ICU admission was the endpoint assessed. The association between continuous variables was carried out using Spearman’s rank correlation coefficient or Spearman’s rho coefficient. Multivariate logistic regression analysis was applied to determine the association between the 372 T/C genetic polymorphism and survival 30 days from ICU admission. Results: Of 275 patients with severe sepsis, 80 had genotype CC, 55 had genotype CT and 140 had genotype TT of the 372 T/C genetic polymorphism of TIMP-1. Patients with the T allele showed higher serum levels of TIMP-1 than patients without the T allele (P = 0.004). Multiple logistic regression analysis showed that the T allele was associated with higher mortality at 30 days (odds ratio = 2.08; 95% confidence interval = 1.06 to 4.09; P = 0.03). Survival analysis showed that patients with the T allele presented lower 30-day survival than patients without the T allele (c2 = 5.77; P = 0.016). We found an association between TIMP-1 levels and levels of MMP-9 (r = -0.19; P = 0.002), MMP-10 (r = 0.55; P

Objective: The oxidant/antioxidant state in septic patients has only been studied in small series. We wished to determine whether malondialdehyde (MDA) serum levels were associated with severity and 30-day mortality in a large series of patients with sepsis. Methods: We performed an observational, prospective, multicenter study in six Spanish Intensive Care Units. Serum levels of MDA were measured in a total of 228 patients (145 survivors and 83 non-survivors) with severe sepsis and 100 healthy controls. Results: Serum levels of MDA were higher in severe septic patients than in healthy controls. Non-surviving septic patients had higher MDA values than survivors. MDA serum levels were associated with severity markers (lactic acid, SOFA, APACHE-II) and coagulation indices. Regression analysis showed that MDA serum levels were associated with 30-day survival (Hazard ratio¿=¿1.05; 95% confidence interval¿=¿1.009–1.091; p¿=¿0.016). Receiver operating characteristic analysis showed that the area under curve of MDA serum levels to predict 30-day survival was 0.62 (95% CI¿=¿0.56–0.69; P¿=¿0.002). The risk of death in septic patients with MDA serum levels above 4.11 nmol/mL was higher than in patients with lower values (Hazard Ratio¿=¿2.43; 95% CI¿=¿1.49–3.94; p

Cytokeratin (CK)-18 is the major intermediate filament protein in the liver and during hepatocyte apoptosis is cleaved by the action of caspases; the resulting fragments are released into the blood as caspase-cleaved cytokeratin (CCCK)-18. Higher circulating levels of CCCK-18 have been found in patients with hepatocellular carcinoma (HCC) than in healthy controls and than in cirrhotic patients. However, it is unknown whether serum CCCK-18 levels before liver transplantation (LT) in patients with HCC could be used as a prognostic biomarker of one-year survival, and this was the objective of our study with 135 patients. At one year after LT, non-survivors showed higher serum CCCK-18 levels than survivors (p = 0.001). On binary logistic regression analysis, serum CCCK-18 levels >384 U/L were associated with death at one year (odds ratio = 19.801; 95% confidence interval = 5.301–73.972; p < 0.001) after controlling for deceased donor age. The area under the receiver operating characteristic (ROC) curve of serum CCCK-18 levels to predict death at one year was 77% (95% CI = 69%–84%; p < 0.001). The new finding of our study was that serum levels of CCCK-18 before LT in patients with HCC could be used as prognostic biomarker of survival.

Previous studies have found higher levels of serum malondialdehyde (MDA) in hepatocellular carcinoma (HCC) patients compared to healthy controls and higher MDA concentrations in tumoral tissue of HCC patients than in non-tumoral tissue. However, the association between pre-transplant serum levels of MDA and survival in HCC patients after liver transplantation (LT) has not been described, and the aim of the present study was to determine whether such an association exists. In this observational study we measured serum MDA levels in 127 patients before LT. We found higher pre-LT serum MDA levels in 15 non-surviving than in 112 surviving patients one year after LT (p = 0.02). Exact binary logistic regression analysis revealed that pre-LT serum levels of MDA over 3.37 nmol/mL were associated with mortality after one year of LT (Odds ratio = 5.38; 95% confidence interval (CI) = from 1.580 to infinite; p = 0.007) adjusting for age of the deceased donor. The main finding of our study was that there is an association between serum MDA levels before LT for HCC and 1-year survival after LT.

Objective— Thrombin induces CD40 ligand (CD40L) and matrix metalloproteinases (MMPs) under inflammatory/prothrombotic conditions. Thrombin and CD40L could modulate endothelial MMP-10 expression in vitro and in vivo. Methods and Results— Human endothelial cells were stimulated with thrombin (0.1–10 U/mL), CD40L (0.25–1 μg/mL), or their combination (thrombin/CD40L) to assess MMP-10 expression and microparticle generation. Thrombin/CD40L elicited higher MMP-10 mRNA (5-fold; P P N -terminal kinase-1 pathways. Thrombin also upregulated the expression of CD40 in endothelial cell surface increasing its availability, thereby favoring its synergistic effects with CD40L. In mice, thrombin/CD40L further increased the aortic MMP-10 expression. Septic patients with systemic inflammation and enhanced thrombin generation (n=60) exhibited increased MMP-10 and soluble CD40L levels associated with adverse clinical outcome. Endothelial and systemic activation by thrombin/CD40L and lipopolysaccharide also increased microparticles harboring MMP-10 and CD40L. Conclusion— Thrombin/CD40L elicited a strong synergistic effect on endothelial MMP-10 expression and microparticles containing MMP-10 in vitro and in vivo, which may represent a new link between inflammation/thrombosis with prognostic implications.

Background Arterial catheterization is a frequent procedure in Intensive Care Units (ICUs). Accidental catheter removal (ACR) can cause severe and potentially life-threatening complications such as severe bleeding and vascular damage. Few data are available on accidental arterial catheter removal, and no studies have been found comparing the incidence of ACR between different arterial catheter sites. Objective To compare the incidence of ACR in femoral and radial arterial catheters. Research design Retrospective study. Setting A polyvalent ICU. Subjects All consecutive patients subjected to femoral or radial arterial catheterization. Measures The incidence of ACR per 100 catheter-days between groups was compared using Poisson regression. We considered ACR as the presence of unintended removal produced by the patient or healthcare personnel. Results A total of 2419 radial and 1085 femoral arterial catheters were inserted and remained in situ during 14,742 and 6497 days, respectively. We detected 45 cases of ACR with the femoral access and 162 cases with the radial access. The ACR rate was lower with the femoral access (4.1% vs 6.7% in the case of the radial access; p = 0.003). Poisson regression analysis confirmed a lower incidence of ACR with the femoral versus the radial access (0.69 vs 1.10 ACR events per 100 catheter-days; OR 0.6, p=0.006, CI95% 0.01-0.83). Conclusions The incidence of ACR was found to be lower with the femoral than with the radial arterial catheters. In order to improve patient safety, it could be interesting to exhaustively monitor the incidence of ACR and adopt preventive measures, since ACR can give rise to serious complications.

n c w c i t q t Catheter-associated bacteremia (CAB) is a frequent cause of nosocomial infection in the critical patient1--4 and implies an increase in both morbidity--mortality and healthcare costs.5--8 The classical method for confirming CAB involves the concomitant isolation of the microorganism in blood cultures obtained by percutaneous puncture and from catheter tip cultures. This conventional procedure has the inconvenience of requiring catheter withdrawal in order to allow tip culture. In this context, there are arguments both in favor and against systematic catheter removal when suspecting CAB. In favor of withdrawal is the fact that many studies have reported a lesser mortality or duration of CAB when the catheter is removed.9--14 However, these studies pose the limitation of having a non-randomized design. In turn, the arguments against catheter withdrawal include: (I) the low yield of systematic catheter tip culture, with positive cultures in under 10% of all cases according to different series15--17; (II) a randomized study has shown that routine catheter removal is not necessary in stable patients.18 The study included patients with suspected CAB, and excluded hemodynamically unstable subjects, immune depressed patients and individuals with signs of local infection. The patients were randomized to either routine catheter removal or catheter maintenance until the

Certain guidelines for the prevention of ventilator-associated pneumonia (VAP) recommend oral care with chlorhexidine, but none refer to the use of a toothbrush for oral hygiene. The role of toothbrush use has received scant attention. Thus, the objective of this study was to compare the incidence of VAP in critical care patients receiving oral care with and without manual brushing of the teeth. This was a randomized clinical trial developed in a 24-bed medical-surgical intensive care unit (ICU). Patients undergoing invasive mechanical ventilation for than 24 h were included. Patients were randomly assigned to receive oral care with or without toothbrushing. All patients received oral care with 0.12 % chlorhexidine digluconate. Tracheal aspirate samples were obtained during endotracheal intubation, then twice a week, and, finally, on extubation. There were no significant differences between the two groups of patients in the baseline characteristics. We found no statistically significant differences between the groups regarding the incidence of VAP (21 of 217 [9.7 %] with toothbrushing vs. 24 of 219 [11.0 %] without toothbrushing; odds ratio [OR] = 0.87, 95 % confidence interval [CI] = 0.469–1.615; p = 0.75). Adding manual toothbrushing to chlorhexidine oral care does not help to prevent VAP in critical care patients on mechanical ventilation.

La bacteriemia asociada a cateter (BAC) es una causa frecuente de infeccion nosocomial en el paciente critico1--4 y conlleva un incremento de la morbi-mortalidad y de los costes asistenciales5--8. El metodo clasico para confirmar la BAC consiste en el aislamiento concomitante del mismo microorganismo en hemocultivos obtenidos por puncion percutanea y en el cultivo de la punta del cateter. Este metodo convencional conlleva el inconveniente de tener que retirar el cateter para proceder al cultivo de la punta. Sin embargo, la retirada sistematica del cateter ante la sospecha de BAC cuenta con argumentos a favor y en contra. El argumento a favor seria que en muchos estudios se ha encontrado una menor mortalidad o duracion de la BAC con la retirada del cateter9--14; pero todos estos estudios presentan la limitacion de no ser randomizados. Entre los argumentos en contra estarian: I) La baja rentabilidad del cultivo sistematico de la punta del cateter, debido a que en diferentes series se ha encontrado un cultivo positivo en menos del 10% de las puntas cultivadas15--17. II) En un estudio randomizado se objetivo que no era necesaria la retirada rutinaria de los cateteres en pacientes estables18. Se incluyeron en el estudio los pacientes con sospecha de BAC y se excluyeron los pacientes hemodinamicamente inestables, inmunodeprimidos o con signos de infeccion local. Los pacientes fueron aleatorizados a la retirada rutinaria de los cateteres o al mantenimiento de los mismos hasta el resultado de los hemocultivos. En el grupo de espera se procedia a la retirada de los cateteres si los hemocultivos eran positivos, si aparecia inestabilidad hemodinamica o si despues de 3-5 dias persistia la sospecha de BAC; pero si no se daba ninguna de estas circunstancias

Current medical knowledge lacks specific information regarding creatine kinase (CK) elevation in influenza A pH1N1 (2009) infection. Primary endpoints were correlation between CK at intensive care unit (ICU) admission and ICU mortality. Secondary endpoints were ICU length of stay (LOS), mechanical ventilation (MV), and requirement of renal replacement techniques (RRT). A prospective multicenter register included all adults admitted for severe acute respiratory insufficiency (SARI) with confirmed pH1N1 in 148 ICUs. Clinical data including demographics, comorbidities, laboratory information, organ involvement, and prognostic data were registered. Post hoc classification of subjects was determined according to CK level. Data are expressed as median (interquartile range). Five hundred and five (505) patients were evaluable. Global ICU mortality was 17.8 % without documented differences between breakpoints. CK ≥500 UI/L was documented in 23.8 % of ICU admissions, being associated with greater renal dysfunction: acute kidney injury (AKI) was more frequent (26.1 versus 17.1 %, p

Background In cardiopulmonary bypass (CPB) patients, fibrinolysis may enhance postoperative inflammatory response. We aimed to determine whether an additional postoperative dose of antifibrinolytic tranexamic acid (TA) reduced CPB-mediated inflammatory response (IR). Methods We performed a randomized, double-blind, dose-dependent, parallel-groups study of elective CPB patients receiving TA. Patients were randomly assigned to either the single-dose group (40 mg/Kg TA before CPB and placebo after CPB) or the double-dose group (40 mg/Kg TA before and after CPB). Results 160 patients were included, 80 in each group. The incident rate of IR was significantly lower in the double-dose-group TA2 (7.5% vs. 18.8% in the single-dose group TA1; P = 0.030). After adjusting for hypertension, total protamine dose and temperature after CPB, TA2 showed a lower risk of IR compared with TA1 [OR: 0.29 (95% CI: 0.10-0.83), (P = 0.013)]. Relative risk for IR was 2.5 for TA1 (95% CI: 1.02 to 6.12). The double-dose group had significantly lower chest tube bleeding at 24 hours [671 (95% CI 549-793 vs. 826 (95% CI 704-949) mL; P = 0.01 corrected-P significant] and lower D-dimer levels at 24 hours [489 (95% CI 437-540) vs. 621(95% CI: 563-679) ng/mL; P = 0.01 corrected-P significant]. TA2 required lower levels of norepinephrine at 24 h [0.06 (95% CI: 0.03-0.09) vs. 0.20(95 CI: 0.05-0.35) after adjusting for dobutamine [F = 6.6; P = 0.014 corrected-P significant]. We found a significant direct relationship between IL-6 and temperature (rho = 0.26; P < 0.01), D-dimer (rho = 0.24; P < 0.01), norepinephrine (rho = 0.33; P < 0.01), troponin I (rho = 0.37; P < 0.01), Creatine-Kinase (rho = 0.37; P < 0.01), Creatine Kinase-MB (rho = 0.33; P < 0.01) and lactic acid (rho = 0.46; P < 0.01) at ICU arrival. Two patients (1.3%) had seizure, 3 patients (1.9%) had stroke, 14 (8.8%) had acute kidney failure, 7 (4.4%) needed dialysis, 3 (1.9%) suffered myocardial infarction and 9 (5.6%) patients died. We found no significant differences between groups regarding these events. Conclusions Prolonged inhibition of fibrinolysis, using an additional postoperative dose of tranexamic acid reduces inflammatory response and postoperative bleeding (but not transfusion requirements) in CPB patients. A question which remains unanswered is whether the dose used was ideal in terms of safety, but not in terms of effectiveness. Current Controlled Trials number ISRCTN: ISRCTN84413719

When the upper airway is bypassed, it cannot contribute to the natural heat and moisture exchange process of inspired gases. The medicinal gases are cold and dry; thus, the use of mechanical ventilation with an artificial airway requires conditioning of the inspired gas. Much controversy exists about what constitutes the appropriate humidity level for inspired gas. Some authors have advocated an absolute humidity level of 44 mg of water vapor/l of gas and recommend the use of heated humidifiers (HH) because they can condition inspired gas to this humidity level. However, others authors have advocated absolute humidity levels of 26–32 mg of water vapor/l of gas and recommend the use of a heat and moisture exchanger (HME) because these devices provide these levels. Besides, there is no evidence concerning the influence of the different humidification systems on the incidence of VAP. In addition, the humidification is cheaper with HMEs than HHs. Thus, the decision to use HMEs can generally be considered based cost-saving; however, in patients with the presence of specific circumstances (such as hypothermia, atelectasis, thick secretions or hemoptysis), the use of HHs can be considered.

Respiratory filters are devices with a high capacity to prevent the passage of microorganisms. The use of respiratory filters interposed in respiratory circuits to avoid ventilator-associated pneumonia (VAP) was proposed after reports between 1952 and 1972 of several outbreaks of respiratory infections attributed to contamination of anesthesia machines; however, none of the reports presented a bacteriological demonstration of a cause-and-effect relationship. The use of respiratory filters has not decreased the incidence of VAP in patients on anesthesia machines and in critically ill patients. Besides, respiratory filters could have some undesirable effects such as the increase of resistance to inspiratory airflow, increase of resistance to expiratory airflow and increase of dead space in the breathing circuit. Thus, the use of respiratory filters is not routinely necessary; however, they should be used in patients with suspected or confirmed highly communicable respiratory infections (such as bacillary pulmonary tuberculosis) and who require mechanical ventilation).

Of the major complication groups in postoperative patients, that of pulmonary ­difficulties is one of the most frequent causes of increased morbidity and mortality. A preventive strategy is necessary to reduce the incidence of pulmonary complications and minimize their clinical repercussions. Atelectasis is a frequent complication in postoperative patients. During mechanical ventilation, atelectasis can occur because medicinal gases are cold and dry. Atelectasis can cause hypoxemia and increase the risk of nosocomial pneumonia. Adequate airway humidification can help prevent the occurrence of atelectasis. The decision to use a heat and moisture exchanger (HME) or heated humidifier (HH) should be made for each patient, based on cost assistance, infection control, and other medical considerations. The decision about the use of HMEs can generally be considered based on cost savings; however, in patients with the presence of specific circumstances (such as hypothermia, atelectasis, thick secretions or hemoptysis), the use of HHs can be considered.

Antimicrobial-impregnated catheters are more expensive than standard catheters (S-C). A higher incidence of catheter-related bloodstream infection (CRBSI) has been found in jugular venous access with tracheostomy than without tracheostomy. The objective of this study was to determine central venous catheter (CVC)-related costs (considering only the cost of the CVC, diagnosis of CRBSI, and antimicrobial agents used to treat CRBSI) using rifampicin–miconazole-impregnated catheters (RM-C) or S-C in jugular venous access with tracheostomy. We performed a retrospective cohort study of patients admitted to the intensive care unit (ICU) with tracheostomy who received one or more jugular venous catheters. RM-C showed a lower incidence of CRBSI compared with S-C (0 vs. 20.16 CRBSI episodes/1,000 catheter-days; odds ratio = 0.05; 95% confidence interval = 0.001–0.32; p < 0.001) and lower CVC-related costs (including the cost of the CVC, diagnosis, and treatment of CRBSI) (€11.46 ± 6.25 vs. €38.11 ± 77.25; p < 0.001) in jugular venous access with tracheostomy. The use of RM-C could reduce CVC-related costs in jugular venous access with tracheostomy. The results of our study may contribute to clinical decision-making and selection of those patients who could benefit from the use of antimicrobial-impregnated catheters.

Data on catheter-related bloodstream infection (CRBSI) in cubital artery access are scarce. Thus, the objective of this study was to compare the incidence of CRBSI in a large series of patients with femoral or cubital artery catheters. We found 11 events of CRBSI in 1085 femoral artery catheters during 6497 days and none in 449 cubital artery catheters during 2709 days. Poisson regression analysis showed a higher incidence of CRBSI in femoral than in cubital artery site access (1.69 vs 0 CRBSI events per 1000 catheter-days; odds ratio 6.41, 95% confidence interval 1.05–infinite; p = 0.02). In conclusion, according to the results of our observational study, cubital artery access could have a lower risk of CRBSI than femoral artery access. However the development of randomized controlled trials is necessary before this conclusion can be definitively established. In addition, it is necessary to consider other potential mechanical complications when decision-making.

The present article is an update of the literature on catheter-related bloodstream infections in ICU patients. A multidisciplinary group of Spanish physicians with an interest in bloodstream infections selected the most important recently published papers produced in the field. One of the members of the group discussed the content of each of the selected papers, with a critical review by other members of the panel. After a review of the state of the art, papers from the fields of epidemiology, causative microorganisms (bacterial and fungal), risk factors and prognosis, pathogenesis, laboratory diagnosis and prevention were discussed by the group.

Received 8 October 2010; returned 9 November 2010; revised 2 December 2010; accepted 6 December 2010Objectives: The impact of oseltamivir on mortality in critically ill patients with 2009 pandemic influenza A(2009 H1N1) is not clear. The main objective of this study was to investigate the relationship between thetiming of antiviral administration and intensive care unit (ICU) outcomes.Methods: Prospective, observational study of a cohort of ICU patients with confirmed 2009 H1N1 infection.Clinical data, treatment and outcome were compared between patients receiving early treatment (ET) withoseltamivir, initiated within 2 days, and patients administered late treatment (LT), initiated after this timepoint.Multivariate analysis and propensity score were used to determine the effect of oseltamivir on ICU mortality.Results: Six hundred and fifty-seven patients were enrolled. Four hundred and four (61.5%) patients requiredmechanical ventilation (MV; mortality 32.6%). Among them, 385 received effective antiviral therapy andwere included in the study group. All patients received oseltamivir for a median duration of 10 days (interquar-tile range 8–14 days). Seventy-nine (20.5%) ET patients were compared with 306 LT patients. The two groupswere comparable in terms of main clinical variables. ICU length of stay (22.7+16.7 versus 18.4+14.2 days;P¼0.03), hospital length of stay (34.0+20.3 versus 27.2+18.2 days; P¼0.001) and MV days (17.4+15.2versus 14.0+12.4; P¼0.04) were higher in the LT group. ICU mortality was also higher in LT (34.3%) than inET (21.5%; OR¼1.9; 95% CI 1.06–3.41). A multivariate model identified ET (OR¼0.44; 95% CI 0.21–0.87) asan independent variable associated with reduced ICU mortality. These results were confirmed by propensityscore analysis (OR¼0.44; 95% CI 0.22–0.90; P,0.001).Conclusions: Our findings suggest that early oseltamivir administration was associated with favourableoutcomes among critically ill ventilated patients with 2009 H1N1 virus infection.Keywords: antiviral treatment, prognosis, pneumonia

The cytopathic hypoxia theory proposes that there is an impaired cellular oxygen utilization during sepsis. Respiratory complex IV, or cytochrome c oxidase, was only previously studied in muscle biopsies of 16 surviving and 12 nonsurviving septic patients. We hypothesized that higher activities and quantities of this enzyme complex could be associated with septic patient survival. The objective was to evaluate the relationship between cytochrome c oxidase activities and quantities and 6-month survival in a larger series of septic patients using a less invasive method (circulating platelets).Prospective, multicenter, observational study.The study was carried out in six Spanish intensive care units.We included 96 septic patients.We determined the cytochrome c oxidase activity per citrate synthase activity ratio and cytochrome c oxidase quantity per citrate synthase activity ratio in circulating platelets at the time of diagnosis and related them to 6-month survival. The written informed consent from the family members was obtained.Survivor patients (n = 54) showed higher cytochrome c oxidase activity per citrate synthase activity ratio (p = .04) and cytochrome c oxidase quantity per citrate synthase activity ratio (p = .006) than nonsurvivors (n = 42). Logistic regression analyses confirmed that the cytochrome c oxidase activity per citrate synthase activity ratio (p = .04) and cytochrome c oxidase quantity per citrate synthase activity ratio (p = .02) were independent predictors of 6-month survival. The area under the curve to predict 6-month survival was 0.62 (95% confidence interval 0.51-0.74; p = .04) for the cytochrome c oxidase activity per citrate synthase activity ratio and 0.67 (95% confidence interval 0.56-0.76; p = .003) for the cytochrome c oxidase quantity per citrate synthase activity ratio. A negative correlation was found between the cytochrome c oxidase quantity per citrate synthase activity ratio and Sepsis-Related Organ Failure Assessment score (p = .04).Platelet cytochrome c oxidase activity and quantity were independent predictors of 6-month survival and could be used as biomarkers of sepsis mortality. This is a rapid, easy, and less invasive protocol to assess mitochondrial function. Patients with lower cytochrome c oxidase activity and quantity could benefit from drugs that improve mitochondrial function.

A higher incidence of catheter-related bloodstream infection (CRBSI) in femoral than in subclavian catheter sites has been found [1,2]. Different guidelines for the prevention of CRBSI recommend avoiding femoral venous access sites [3,4]. However, the incidence of CRBSI in subclavian sites in the presence of tracheostomy is higher than without tracheostomy [5,6]. In addition, the incidence of CRBSI in jugular sites with tracheostomy is higher than in femoral sites [7]. Currently, there are no comparative data on the incidence of CRBSI between the femoral venous and the subclavian venous catheter site in the presence of tracheostomy and there are no recommendations in the guidelines relating to this circumstance; and this was the objective of the present study.

INTRODUCTION: CD40 Ligand (CD40L) and its soluble counterpart (sCD40L) are proteins that exhibit prothrombotic and proinflammatory properties on binding to their cell surface receptor CD40. The results of small clinical studies suggest that sCD40L levels could play a role in sepsis; however, there are no data on the association between sCD40L levels and mortality of septic patients. Thus, the aim of this study was to determine whether circulating sCD40L levels could be a marker of adverse outcome in a large cohort of patients with severe sepsis. METHODS: This was a multicenter, observational and prospective study carried out in six Spanish intensive care units. Serum levels of sCD40L, tumour necrosis factor-alpha and interleukin-10, and plasma levels of tissue factor were measured in 186 patients with severe sepsis at the time of diagnosis. Serum sCD40L was also measured in 50 age- and sex-matched controls. Survival at 30 days was used as the endpoint. RESULTS: Circulating sCD40L levels were significantly higher in septic patients than in controls (P = 0.01), and in non-survivors (n = 62) compared to survivors (n = 124) (P = 0.04). However, the levels of CD40L were not different regarding sepsis severity. Logistic regression analysis showed that sCD40L levels >3.5 ng/mL were associated with higher mortality at 30 days (odds ratio = 2.89; 95% confidence interval = 1.37 to 6.07; P = 0.005). The area under the curve of sCD40L levels >3.5 ng/mL as predictor of mortality at 30 days was 0.58 (95% CI = 0.51 to 0.65; P = 0.03). CONCLUSIONS: In conclusion, circulating sCD40L levels are increased in septic patients and are independently associated with mortality in these patients; thus, its modulation could represent an attractive therapeutic target.

In the past 2 years, American, Canadian, and European scientific societies have published their new evidence-based guidelines for ventilator-associated pneumonia (VAP) prevention. However, these guidelines did not review some potentially useful strategies, such as the use of an endotracheal tube with an ultrathin cuff membrane, an endotracheal tube with a low-volume/low-pressure cuff, a device for continuous monitoring of the endotracheal tube cuff pressure, a device to remove biofilm from the inner site of the endotracheal tube, and saline instillation before tracheal suctioning. Only a few guidelines analyze the time of tracheostomy, and so no firm recommendations can be made regarding its importance. In addition, the guidelines diverge on the use of heat and moisture exchangers or heated humidifiers and on the use of an endotracheal tube coated with antimicrobial agents. The current review focuses on measures of VAP prevention for which there is no clear recommendation, or the use of which is controversial. A review of the literature suggests that the use of an endotracheal tube with an ultrathin and tapered-shape cuff membrane and coated in antimicrobial agents may reduce the risk of VAP. These features offer an attractive way to optimize the VAP prevention capacity of endotracheal tubes with a lumen for subglottic secretion drainage. We believe that early tracheostomy should be considered, based on the length reduction of mechanical ventilation and intensive care unit stay, reduction of mortality, and on patient comfort, although early tracheostomy has not yet been shown to favorably impact the incidence of VAP. We believed that heat and moisture exchangers should be considered based on the benefits in terms of cost savings. More research is necessary to clarify the role of continuous cuff pressure monitoring, removal of biofilm formation in the endotracheal tubes, and routine saline instillation before tracheal suctioning.

We read with interest the commentary by Hoff mann and colleagues [1] on our manuscript recently published in Critical Care showing that matrix metalloproteinase (MMP)-9, MMP-10 and tissue inhibitor of matrix metalloproteinases (TIMP)-1 could be new biomarkers of severity and mortality in sepsis [2]. As they stated, the lack of serial measurements of MMPs and TIMPs over clinical evolution was as a limitation of our study. Despite this limitation, our results suggest that MMPs and TIMPs may be of pathophysiological signifi cance in sepsis. Some clinical studies have found higher circulating levels of MMP-9 [2-4] and TIMP-1 [2,3] in septic patients than in healthy controls, and higher levels of TIMP-1 [2,3] or MMP-9 [4] in nonsurviving than in surviving septic patients. Our study also reports, for the fi rst time, that MMP-10 circulating levels are also elevated in septic patients [2]. According to the results of some in vitro studies, MMP-10 could play a role in infection, since increased MMP-10 gene transcription was observed after infective stimulation of human and mice cells. On the other hand, we think the correlation between MMP-9, TIMP-1 and markers of coagulopathy, and the lower MMP-9/TIMP-1 ratio in nonsurviving than in surviv ing septic patients found in our study, may be associated with a higher prothrombotic/antifi brinolytic state, responsible for the capillary thrombosis, multiple organ dysfunction, and death. Finally, from a therapeutic perspective, the development of modulators of MMP/TIMP activity could be used as a new class of drugs for the treatment of severe sepsis [5].

The second most important infectious complication in hospitalized patients is pneumonia, this occupying the first place in the Intensive Care Units (ICU). Approximately 80% of the episodes of nosocomial pneumonia occur in patients with an artificial airway, which is called ventilation-associated pneumonia (VAP). VAP is the most frequent cause of mortality among nosocomial infections in the ICU, mainly if they are caused by Pseudomonas aeruginosa and Methicillin-resistant Staphylococcus aureus (MRSA). It also increases days of mechanical ventilation and length of stay in the ICU and hospital. In spite of the available diagnostic procedures, the diagnosis of VAP continues to be a clinical one. The presence of X-ray infiltrates and purulent endotracheal secretions are the essential conditions for the diagnosis. We should also evaluate the patient's condition and the risk factors for difficult-to-treat pathogens. If the VAP is early and there are no risk factors, most of the empiric antibiotic strategies will provide correct coverage of the flora found. However, if the diagnosis of VAP is made in a patient who has been receiving mechanical ventilation for more than one week, under antibiotic use, with risk factors for multi-resistant pathogens, we should individualize the empiric antibiotic treatment.

Recent guidelines do not establish a recommendation about the arterial catheter site to minimize the arterial catheter-related infection risk. In this prospective and observational study, we found a higher arterial catheter-related infection in 1085 arterial femoral sites than in 141 arterial brachial sites (5.08 vs 0 per 1000 catheter-days, respectively; odds ratio, 6.18; 95% confidence interval: 1.11-infinite; P = .02). Thus, arterial brachial access should be used in preference to femoral access.

Introduction and objectives Postoperative atrial fibrillation is a common complication of carrying out cardiac surgery with extracorporeal circulation (ECC). The aim of this study was to determine whether preoperative left atrial contractile dysfunction, as assessed by tissue Doppler echocardiography, is associated with the development of postoperative new-onset atrial fibrillation (PAF). Methods Transthoracic Doppler echocardiography was performed preoperatively in patients undergoing elective cardiac surgery. Left atrial contractile function was evaluated by tissue Doppler imaging (TDI) of the mitral annulus. Results The study included 92 patients in sinus rhythm preoperatively who underwent elective cardiac surgery with ECC: 73 (79%) were male and 19 (21%) were female, and their mean age was 67 (10) years. Of these, 19 (20.6%) developed PAF 34 (12) h postoperatively. Bivariate analysis showed that PAF was associated with older age (71 [7] years vs 66 [10] years; P =.034), a large left atrial diameter (LAD), and a low peak atrial systolic mitral annular velocity (A velocity) and a high mitral E/A ratio on TDI. Logistic regression analysis showed that PAF was independently associated with a large LAD (odds ratio [OR] =2.23; 95% confidence interval [CI], 1.05-4.76; P =.033) and a low A velocity (OR=0.70; 95% CI, 0.55-0.99; P =.034). Conclusions Preoperative left atrial dysfunction, as assessed by TDI, was associated with an increased risk of PAF.

En las guidelines para la prevención de la bacteriemia relacionada con catéter venoso central (BCVC) de los Centers for Disease Control and Prevention (CDC) de 2002, de la Sociedad Española de Medicina Intensiva, Crítica y Unidades Coronarias/ Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica (SEMICYUC/SEIMC) de 2004, y en las recientemente publicadas guidelines de la Society for Healthcare Epidemiology of America/Infectious Diseases Society of America (SHEA/IDSA) de 2008 se recomienda utilizar preferentemente la vena subclavia y evitar la femoral, y considerar el uso de CVC impregnados en antisépticos o antimicrobianos en unidades hospitalarias o grupos de pacientes que tienen una alta incidencia de BCVC. A la hora de la implantación de estas guidelines podrían plantearse dos preguntas: 1) ¿el abuso de la vena subclavia y el desuso de la femoral podrían conllevar una disminución de la incidencia de BCVC pero un aumento de la tasa de complicaciones mecánicas como neumotórax o hemotórax?, y 2) ¿no se podrían utilizar catéteres impregnados en antimicrobianos para prevenir la BCVC cuando se utilice la vena femoral?

INTRODUCTION: Matrix metalloproteinases (MMPs) play a role in infectious diseases through extracellular matrix (ECM) degradation, which favors the migration of immune cells from the bloodstream to sites of inflammation. Although higher levels of MMP-9 and tissue inhibitor of matrix metalloproteinases-1 (TIMP-1) have been found in small series of patients with sepsis, MMP-10 levels have not been studied in this setting. The objective of this study was to determine the predictive value of MMP-9, MMP-10, and TIMP-1 on clinical severity and mortality in a large series of patients with severe sepsis. METHODS: This was a multicenter, observational, and prospective study carried out in six Spanish Intensive Care Units. We included 192 (125 surviving and 67 nonsurviving) patients with severe sepsis and 50 age- and sex-matched healthy controls in the study. Serum levels of MMP-9, MMP-10, TIMP-1, tumor necrosis factor (TNF)-alpha, and interleukin (IL)-10 were measured in patients with severe sepsis at the time of diagnosis and in healthy controls. RESULTS: Sepsis patients had higher levels of MMP-10 and TIMP-1, higher MMP-10/TIMP-1 ratios, and lower MMP-9/TIMP-1 ratios than did healthy controls (P < 0.001). An association was found between MMP-9, MMP-10, TIMP-1, and MMP-9/TIMP-1 ratios and parameters of sepsis severity, assessed by the SOFA score, the APACHE-II score, lactic acid, platelet count, and markers of coagulopathy. Nonsurviving sepsis patients had lower levels of MMP-9 (P = 0.037), higher levels of TIMP-1 (P < 0.001), lower MMP-9/TIMP-1 ratio (P = 0.003), higher levels of IL-10 (P < 0.001), and lower TNF-alpha/IL-10 ratio than did surviving patients. An association was found between MMP-9, MMP-10, and TIMP-1 levels, and TNF-alpha and IL-10 levels. The risk of death in sepsis patients with TIMP-1 values greater than 531 ng/ml was 80% higher than that in patients with lower values (RR = 1.80; 95% CI = 1.13 to 2.87;P = 0.01; sensitivity = 0.73; specificity = 0.45). CONCLUSIONS: The novel findings of our study on patients with severe sepsis (to our knowledge, the largest series reporting data about MMP levels in sepsis) are that reduced MMP-9/TIMP-1 ratios and increased MMP-10 levels may be of great pathophysiologic significance in terms of severity and mortality, and that TIMP-1 levels may represent a biomarker to predict the clinical outcome of patients with sepsis.

Summary Although there are many studies on arterial catheter-related infection (ACRI) there is little information on the relative risks associated with different catheter access sites. In previous studies we have shown a higher incidence of ACRI in femoral than in radial access sites. This prospective observational study was designed to compare the incidence of ACRI in patients on an intensive care unit with femoral versus dorsalis pedis access sites. We compared 1085 femoral arterial catheters inserted for a cumulative 6497 days with 174 dorsalis pedis catheters inserted for a cumulative 1050 days. We detected 33 cases of ACRI in the femoral access group (11 with bacteraemia and 22 with line site infection; 5.08 infections per 1000 catheter-days) but none in the dorsalis pedis access group. There were no significant differences between the two groups regarding age, sex, Acute Physiological Assessment and Chronic Health Evaluation (APACHE) II, diagnosis, previous arterial catheter insertion, use of mechanical ventilation, use of antimicrobials or catheter duration. Regression analysis showed a higher incidence of ACRI for femoral than for dorsalis pedis access sites (odds ratio: 7.6; 95% confidence interval: 1.37–infinite; P =0.01). These results suggest that dorsalis pedis arterial access should be used in preference to femoral arterial access in order to reduce the risk of ACRI.

Plasminogen activator inhibitor 1 (PAI-1) attenuates the conversion of plasminogen to plasmin. Polymorphisms of the PAI-1 gene are associated with varying PAI-1 levels and risk of prothrombotic events in nonsurgical patients. The purpose of this study, a secondary analysis of a clinical trial, was to investigate whether PAI-1 genotype affects the efficacy of tranexamic acid (TA) in reducing postoperative chest tube blood loss of patients undergoing cardiopulmonary bypass.Fifty patients were classified according to PAI-1 genotype (4G/4G, 4G/5G, or 5G/5G). Twenty-four received 2 g TA before and after cardiopulmonary bypass, whereas 26 received placebo. The authors recorded data related to coagulation, fibrinolysis, and bleeding before surgery, at admission to the intensive care unit (0 h), and 4 and 24 h later.In patients not receiving TA, those with the 5G/5G genotype had significantly higher chest tube blood loss and transfusion requirements compared with patients with the other genotypes at all time points. Patients with the 5G/5G genotype receiving TA showed significantly lower blood loss compared with the placebo group. There were no significant differences in blood loss or transfusion requirements between patients with the 4G/4G genotype when TA was used.Plasminogen activator inhibitor-1 5G/5G homozygotes who did not receive TA showed significantly greater postoperative bleeding than patients with other PAI-1 genotypes. 5G/5G homozygotes who received TA showed the greatest blood-sparing benefit.

Beta-lactam antibiotics are reported to exhibit time-dependent bactericidal activity. However, there are limited data on the clinical efficacy of ceftazidime administered by continuous infusion.The objective of this study was to compare the clinical efficacy of ceftazidime administered by continuous infusion and by intermittent infusion in the treatment of ventilator-associated pneumonia (VAP) caused by gram-negative bacteria.This was a retrospective chart review of patients with VAP caused by gram-negative bacteria who were treated with initial empiric ceftazidime therapy in the intensive care unit (ICU) over a 5-year period (from June 2002 to June 2007). The intermittent-infusion group received ceftazidime 2 g infused over 30 minutes every 12 hours; the continuous-infusion group received a ceftazidime loading dose of 1 g over 30 minutes, followed by 2 g infused over 720 minutes every 12 hours. Data extracted from patients' charts included sex, age, severity of the patient's condition at ICU admission (Acute Physiology and Chronic Health Evaluation II [APACHE II] score), diagnosis group, weight, creatinine clearance, MIC of the organism responsible for VAP, and severity of organ dysfunction at the time VAP was suspected (Sepsis-related Organ Failure Assessment [SOFA] score). Each clinical history was reviewed by a group of 6 staff intensivists who were blinded to whether the patient received ceftazidime by continuous or intermittent infusion. The clinical effect of treatment was categorized as cure (complete resolution of all clinical signs and symptoms of pneumonia) or failure (persistence or progression of any sign or symptom of pneumonia).The final sample consisted of 121 patients, of whom 88 (72.7%) were males. The mean (SD) age of the population was 62.87 (9.35) years. The mean APACHE II score on admission to the ICU was 16.08 (2.17), the SOFA score at suspicion of VAP was 8.80 (2.06), and the MIC of the organism responsible for VAP was 2.77 (2.24) microg/mL. There were no significant differences in these and other characteristics at baseline between those who received ceftazidime by continuous infusion (n = 56) and those who received ceftazidime by intermittent infusion (n = 65). On logistic regression analysis, continuous infusion was associated with a greater clinical cure rate than intermittent infusion (50/56 [89.3%] vs 34/65 [52.3%], respectively; odds ratio [OR] = 12.2; 95% CI, 3.47-43.21; P0.001). Patients with VAP caused by organisms with an MIC of 8 microg/mL had lower cure rates compared with those with VAP caused by organisms with an MICor =2 microg/mL (OR = 0.2; 95% CI, 0.04-0.71; P = 0.02) but not compared with those with an MIC of 4 microg/mL. No significant interaction was found between the type of ceftazidime infusion and the MIC of the causative organism.In this small, selected population of adult patients with VAP caused by gram-negative bacteria who were treated in a nonrandomized, open-label manner, ceftazidime administered by continuous infusion had greater clinical efficacy than ceftazidime administered by intermittent infusion.

IntroductionExcessive bleeding (EB) after cardiopulmonary bypass (CPB) may lead to increased mortality, morbidity, transfusion requirements and re-intervention. Less than 50% of patients undergoing re-intervention exhibit surgical sources of bleeding. We studied clinical and genetic factors associated with EB.MethodsWe performed a nested case-control study of 26 patients who did not receive antifibrinolytic prophylaxis. Variables were collected preoperatively, at intensive care unit (ICU) admission, at 4 and 24 hours post-CPB. EB was defined as 24-hour blood loss of >1 l post-CPB. Associations of EB with genetic, demographic, and clinical factors were analyzed, using SPSS-12.2 for statistical purposes.ResultsEB incidence was 50%, associated with body mass index (BMI)< 26.4 (25–28) Kg/m2, (P= 0.03), lower preoperative levels of plasminogen activator inhibitor-1 (PAI-1) (P= 0.01), lower body temperature during CPB (P= 0.037) and at ICU admission (P= 0.029), and internal mammary artery graft (P= 0.03) in bypass surgery. We found a significant association between EB and 5G homozygotes for PAI-1, after adjusting for BMI (F = 6.07;P= 0.02) and temperature during CPB (F = 8.84;P= 0.007). EB patients showed higher consumption of complement, coagulation, fibrinolysis and hemoderivatives, with significantly lower leptin levels at all postoperative time points (P= 0.01,P< 0.01 andP< 0.01).ConclusionExcessive postoperative bleeding in CPB patients was associated with demographics, particularly less pronounced BMI, and surgical factors together with serine protease activation.

Objective Melatonin in septic patients has been scarcely explored and only in studies of small sample size (maximum 20 patients). Thus, the objective of this study was to determine whether serum melatonin levels are associated with severity, oxidant and inflammatory state, and mortality in a large series of septic patients. Methods A prospective, observational, multicenter study was performed in 6 Spanish intensive care units with 201 severe septic patients. Serum levels of melatonin were measured at moment of severe sepsis diagnosis. The end point was 30-day mortality. Results Non-surviving patients (n = 71) showed higher serum melatonin levels (P Conclusions The novel finding of our study was that serum melatonin levels are associated with mortality in septic patients.

The oxidative phosphorylation system (OXPHOS) in septic patients has been scarcely analyzed in studies of small sample size and the results are apparently inconsistent. Previously, including 96 severe septic patients, we found that nonsurviving severe septic patients showed lower platelet respiratory complex IV (CIV) activity than surviving patients at the moment of severe sepsis diagnosis and during the first week of sepsis diagnosis. However, we did not examine this enzyme activity in normal individuals. Thus, the objective of this study was to compare the CIV activity between severe septic patients and healthy control individuals in a larger series of patients (including 198 severe septic patients).

Introduction Some guidelines to prevent ventilator-associated pneumonia (VAP) do not establish a recommendation for the preferential use of either heat and moisture exchangers (HMEs) or heated humidifiers (HHs), while other guidelines clearly advocate the use of HMEs. The aim of this study was to determine the incidence of VAP associated with HHs or HMEs. Methods A randomized study was conducted in the intensive care unit of a university hospital involving patients expected to require mechanical ventilation for >5 days. Patients were assigned to two groups; one group received HH and the other group received HME. Tracheal aspirate samples were obtained on endotracheal intubation, then twice a week, and finally on extubation, in order to diagnose VAP. Throat swabs were taken on admission to the intensive care unit, then twice a week, and finally at discharge from the intensive care unit in order to classify VAP as primary endogenous, secondary endogenous, or exogenous. Results A total of 120 patients were assigned to HMEs (60 patients) and HHs (60 patients); 16 patients received mechanical ventilation for less than five days and were excluded from the analysis. Data analysis of the remaining 104 patients (53 HMEs and 51 HHs) showed no significant differences between groups regarding sex, age, Acute Physiology and Chronic Health Evaluation II score, pre-VAP use of antibiotics, days on mechanical ventilation, and diagnosis group. VAP was found in eight of 51 (15.69%) patients in the HH group and in 21 of 53 (39.62%) patients in the HME group (P = 0.006). The median time free of VAP was 20 days (95% confidence interval, 13.34–26.66) for the HH group and was 42 days (95% confidence interval, 35.62–48.37) for the HME group (P

Introduction Central venous catheterization is commonly used in critically ill patients and may cause different complications, including infection. Although there are many studies about CVC-related infection, very few have analyzed it in detail. The objective of this study was to analyze the incidence of catheter-related local infection (CRLI) and catheter-related bloodstream infection (CRBSI) with central venous catheters (CVCs) according to different access sites. Methods This is a prospective and observational study, conducted in a 24-bed medical surgical intensive care unit of a 650-bed university hospital. All consecutive patients admitted to the ICU during 3 years (1 May 2000 and 30 April 2003) were included. Results The study included 2,018 patients. The number of CVCs and days of catheterization duration were: global, 2,595 and 18,999; subclavian, 917 and 8,239; jugular, 1,390 and 8,361; femoral, 288 and 2,399. CRLI incidence density was statistically higher for femoral than for jugular (15.83 versus 7.65, p < 0.001) and subclavian (15.83 versus 1.57, p < 0.001) accesses, and higher for jugular than for subclavian access (7.65 versus 1.57, p < 0.001). CRBSI incidence density was statistically higher for femoral than for jugular (8.34 versus 2.99, p = 0.002) and subclavian (8.34 versus 0.97, p < 0.001) accesses, and higher for jugular than for subclavian access (2.99 versus 0.97, p = 0.005). Conclusion Our results suggest that the order for punction, to minimize the CVC-related infection risk, should be subclavian (first order), jugular (second order) and femoral vein (third order).

The aim of this study was to analyze the prevalence of ventilator-associated pneumonia (VAP) using a closed-tracheal suction system vs. an open system.Prospective and randomized study, from October 1, 2002, to December 31, 2003.A 24-bed medical-surgical intensive care unit in a 650-bed tertiary hospital.Patients requiring mechanical ventilation for24 hrs.Patients were randomized into two groups; one group was suctioned with the closed-tracheal suctioning system and another group with the open system.Throat swabs were taken at admission and twice a week until discharge to classify pneumonia in endogenous and exogenous.A total of 443 patients (210 with closed-tracheal suction system and 233 with the open system) were included. There were no significant differences between groups of patients in age, sex, diagnosis groups, mortality, number of aspirations per day, and Acute Physiology and Chronic Health Evaluation II score. No significant differences were found in either the percentage of patients who developed VAP (20.47% vs. 18.02%) or in the number of VAP cases per 1000 mechanical ventilation-days (17.59 vs. 15.84). There were also no differences in the VAP incidence by mechanical ventilation duration. At the same time, we did not find any differences in the incidence of exogenous VAP. Likewise, there were also no differences in the microorganisms responsible for pneumonia. Patient cost per day for the closed suction was more expensive than the open suction system (11.11 US dollars +/- 2.25 US dollars vs. 2.50 US dollars +/- 1.12 US dollars, p.001).We conclude that in our study, the closed-tracheal suction system did not reduce VAP incidence, even for exogenous pneumonia.

To describe the incidence of the catheter-related local infection (CRLI) and catheter-related bloodstream infection (CRBSI) of central venous catheters (CVCs) and arterial catheters (ACs). Prospective, observational study. A 24-bed medical-surgical intensive care unit of a 650-bed university hospital. We included 988 consecutive patients admitted to the ICU during 18 months. The incidence density of CRLI and CRBSI, per 1000 catheter-days, of CVC and AC. Central venous catheters had a significantly higher incidence density of CRLI (4.74 vs 0.97/1,000 catheter-days; p

Commentary on : Safdar N, O'Horo JC, Ghufran A, et al. Chlorhexidine-impregnated dressing for prevention of catheter-related bloodstream infection: a meta-analysis. Crit Care Med 2014;42:1703–13.[OpenUrl][1][CrossRef][2][PubMed][3][Web of Science][4] Intravascular catheters (IVC) are commonly used in hospitalised patients. However, the use of such catheters could entail infectious complications. Catheter-related bloodstream infection (CRBSI) has been associated with increased morbidity, mortality and … [1]: {openurl}?query=rft.jtitle%253DCrit%2BCare%2BMed%26rft.volume%253D42%26rft.spage%253D1703%26rft_id%253Dinfo%253Adoi%252F10.1097%252FCCM.0000000000000319%26rft_id%253Dinfo%253Apmid%252F24674924%26rft.genre%253Darticle%26rft_val_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Ajournal%26ctx_ver%253DZ39.88-2004%26url_ver%253DZ39.88-2004%26url_ctx_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Actx [2]: /lookup/external-ref?access_num=10.1097/CCM.0000000000000319&link_type=DOI [3]: /lookup/external-ref?access_num=24674924&link_type=MED&atom=%2Febnurs%2F18%2F3%2F91.atom [4]: /lookup/external-ref?access_num=000337703000035&link_type=ISI

Objective Higher values of red blood cell distribution width (RDW) have been found in non-surviving than in surviving septic patients. However, it is unknown whether RDW during the first week of sepsis evolution is associated with sepsis severity and early mortality, oxidative stress and inflammation states, and these were the aims of the study. Methods We performed a prospective, observational, multicenter study in six Spanish Intensive Care Units with 297 severe septic patients. We measured RDW, serum levels of malondialdehyde (MDA) to assess oxidative stress, and tumour necrosis factor (TNF)-α to assess inflammation at days 1, 4, and 8. The end-point was 30-day mortality. Results We found higher RDW in non-surviving (n = 104) than in surviving (n = 193) septic patients at day 1 (p = 0.001), day 4 (p = 0.001), and day 8 (p = 0.002) of ICU admission. Cox regression analyses showed that RDW at day 1 (p

Introduction In a previous study with 96 septic patients, we found that circulating platelets in 6-months surviving septic patients showed higher activity and quantity of cytochrome c oxidase (COX) normalized by citrate synthase (CS) activity at moment of severe sepsis diagnosis than non-surviving septic patients. The objective of this study was to estimate whether COX specific activity during the first week predicts 1-month sepsis survival in a larger cohort of patients. Methods Using a prospective, multicenter, observational study carried out in six Spanish intensive care units with 198 severe septic patients, we determined COX activity per proteins (COXact/Prot) in circulating platelets at day 1, 4 and 8 of the severe sepsis diagnosis. Endpoints were 1-month and 6-months mortality. Results Survivor patients (n = 130) showed higher COXact/Prot (P 0.30 mOD/min/mg at day 1 (P = 0.002), 4 (P = 0.006) and 8 (P = 0.02) was associated independently with 1-month mortality. Area under the curve of COXact/Prot at day 1, 4 and 8 to predict 30-day survival were 0.70 (95% CI = 0.63-0.76; P

Sir: Although arterial catheter-related infection (AC-RI) has been amply reported [1, 2], we have found no study reporting the micro-organisms responsible according to femoral and radial access. We therefore analyzed this as a part of our recently published study [3], such as we have lately done with central venous catheter-related infection [4]. An initial analysis of 1,231 arterial catheters inserted during 18months revealed no significant differences in the incidence of arterial catheter-related bloodstream infections (AC-RBSI) and of arterial catheter-related local infections (ACRLI) according to catheter site [5]. In a second analysis of 2,949 arterial catheters inserted over 3 years, however, we found that the incidence

In the previous issue of Critical Care, Behnes and colleagues [1] provide an interesting commentary on our study showing that septic patients with the T-allele in 372 T/C (rs4898) genetic polymorphism of the tissue inhibitor of metalloproteinase-1 (TIMP-1) had higher mortality and higher TIMP-1 serum levels than those without it [2]. As the authors state in their commentary, our study had some limitations. One limitation was the relatively small sample size to establish prognostic implications by only one single-nucleotide polymorphism (SNP) challenge. However, the sample size was large enough to find an association between polymorphism and survival. Another limitation was that we tested only the rs4898 SNP, a tag SNP, for the region of interest. However, it may be that this SNP, which is in strong linkage disequilibrium with other TIMP-1 polymorphisms, is linked to other SNPs associated with the same effect. Another possibility is that this association represents only an epiphenomenon since, in our study, a cause-effect relationship between polymorphism and mortality was not established. However, we found that patients with the T-allele had higher TIMP-1 serum levels and that patients with higher TIMP-1 circulating levels showed higher mortality [3,4]. Besides, we found a positive association between TIMP-1 and plasminogen activator inhibitor-1 circulating levels, previously found in myocardial infarction patients [5], probably suggesting a prothrombotic state. In conclusion, we think that the determinations of 372 T/C genetic polymorphism and circulating levels of TIMP-1 could be used as mortality biomarkers in patients with sepsis.