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).

Rationale: Subglottic secretion drainage (SSD) appears to be effective in preventing ventilator-associated pneumonia (VAP), primarily by reducing early-onset pneumonia; but it may not prevent late-onset pneumonia. We tested the hypothesis using an endotracheal tube incorporating an ultrathin polyurethane cuff (which reduces channel formation and fluid leakage from the subglottic area), in addition to an SSD lumen, which would reduce the incidence of late-onset VAP. Objectives: To compare the incidence of VAP, using an endotracheal tube with polyurethane cuff and subglottic secretion drainage (ETT-PUC-SSD) versus a conventional endotracheal tube (ETT-C) with polyvinyl cuff, without subglottic secretion drainage. Methods: Clinical randomized trial in a 24-bed medical–surgical intensive care unit. Patients expected to require mechanical ventilation for more than 24 hours were randomly assigned to one of two groups: one was ventilated with ETT-PUC-SSD and the other with ETT-C. Measurements and Main Results: Tracheal aspirate samples were obtained during endotracheal intubation, then twice per week and finally on extubation. VAP was found in 31 of 140 (22.1%) patients in the ETT-C group and in 11 of 140 (7.9%) in the ETT-PUC-SSD group (P = 0.001). Cox regression analysis showed ETT-C as a risk factor for global VAP (hazard ratio [HR], 3.3; 95% confidence interval [CI], 1.66–6.67; P = 0.001), early-onset VAP (HR, 3.3; 95% CI, 1.19–9.09; P = 0.02), and late-onset VAP (HR, 3.5; 95% CI, 1.34–9.01; P = 0.01). Conclusions: The use of an endotracheal tube with polyurethane cuff and subglottic secretion drainage helps prevent early- and late-onset VAP. Clinical trial registered with www.clinicaltrials.gov (NCT00475579).

Introduction: Extracorporeal circulation induces hemostatic alterations that lead to inflammatory response (IR) and postoperative bleeding. Tranexamic acid (TA) reduces fibrinolysis and blood loss after cardiopulmonary bypass (CPB). However, its effects on IR and vasoplegic shock (VS) are not well known and elucidating these effects was the main objective of this study. Methods: A case control study was carried out to determine factors associated with IR after CPB. Patients undergoing elective CPB surgery were randomly assigned to receive 2 g of TA or placebo (0.9% saline) before and after intervention. We performed an intention-to-treat analysis, comparing the incidence of IR and VS. We also analyzed several biological parameters related to inflammation, coagulation, and fibrinolysis systems. We used SPSS version 12.2 for statistical purposes. Results: In the case control study, 165 patients were studied, 20.6% fulfilled IR criteria, and the use of TA proved to be an independent protective variable (odds ratio 0.38, 95% confidence interval 0.18 to 0.81; P < 0.01). The clinical trial was interrupted. Fifty patients were randomly assigned to receive TA (24) or placebo (26). Incidence of IR was 17% in the TA group versus 42% in the placebo group (P = 0.047). In the TA group, we observed a significant reduction in the incidence of VS (P = 0.003), the use of norepinephrine (P = 0.029), and time on mechanical ventilation (P = 0.018). These patients showed significantly lower D-dimer, plasminogen activator inhibitor 1, and creatine-kinase levels and a trend toward lower levels of soluble tumor necrosis factor receptor and interleukin-6 within the first 24 hours after CPB. Conclusion: The use of TA attenuates the development of IR and VS after CPB. Trial registration number: ISRCTN05718824.

Background: It is known that β-lactam antibiotics exhibit time-dependent bactericidal activity. Several studies have found continuous infusion of meropenem more effective than intermittent infusion in maintaining constant serum concentrations in excess of the minimum inhibitory concentration. However, limited data exist on the clinical efficacy of meropenem administered by continuous infusion. Objective: To evaluate the clinical efficacy of continuous versus intermittent infusion of meropenem for the treatment of ventilator-associated pneumonia (VAP) due to gram-negative bacilli. Methods: A retrospective cohort study was conducted of patients with VAP caused by gram-negative bacilli who received initial empiric antibiotic therapy with meropenem. We analyzed 2 contemporary cohorts: one group received meropenem by continuous infusion (1 g over 360 min every 6 h), the other by intermittent infusion (1 g over 30 min every 6 h). The administration method was prescribed according to the physician's discretion. Patients received meropenem plus tobramycin for 14 days. Results: There were no significant differences between patient groups with regard to gender, age, APACHE-II at intensive care unit admission, diagnosis, microorganism responsible for VAP, or organ dysfunction severity at the time VAP was suspected. The group receiving medication by continuous infusion showed a greater clinical cure rate than the group treated with intermittent infusion (38 of 42, 90.47%, vs 28 of 47, 59.57%, respectively, with OR 6.44 [95% Cl 1.97 to 21.05; p < 0.001]). Conclusions: Meropenem administered by continuous infusion may have more clinical efficacy than intermittent infusion.

Ventilator-associated pneumonia (VAP) continues to be an important cause of morbidity and mortality in ventilated patients.Evidence-based guidelines have been issued since 2001 by the European Task Force on ventilator-associated pneumonia, the Centers for Disease Control and Prevention, the Canadian Critical Care Society, and also by the American Thoracic Society and Infectious Diseases Society of America, which have produced a joint set of recommendations.The present review article is based on a comparison of these guidelines, together with an update of further publications in the literature. The 100,000 Lives campaign, endorsed by leading US agencies and societies, states that all ventilated patients should receive a ventilator bundle to reduce the incidence of VAP.The present review article is useful for identifying evidence-based processes that can be modified to improve patients' safety.

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-α/IL-10 ratio than did surviving patients. An association was found between MMP-9, MMP-10, and TIMP-1 levels, and TNF-α 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.