Trisodium citrate 4% versus heparin as a catheter lock for non-tunneled hemodialysis catheters in critically ill patients: a multicenter, randomized clinical trial.

BACKGROUND: Non-tunneled hemodialysis catheters are currently used for critically ill patients with acute kidney injury requiring extracorporeal renal replacement therapy. Strategies to prevent catheter dysfunction and infection with catheter locks remain controversial. METHODS: In a multicenter, randomized, controlled, double-blind trial, we compared two strategies for catheter locking of non-tunneled hemodialysis catheters, namely trisodium citrate at 4% (intervention group) versus unfractionated heparin (control group), in patients aged 18 years or older admitted to the intensive care unit and in whom a first non-tunneled hemodialysis catheter was to be inserted by the jugular or femoral vein. The primary endpoint was length of event-free survival of the first non-tunneled hemodialysis catheter. Secondary endpoints were: rate of fibrinolysis, incidence of catheter dysfunction and incidence of catheter-related bloodstream infection (CRBSI), all per 1000 catheter-days; number of hemorrhagic events requiring transfusion, length of stay in intensive care and in hospital; 28-day mortality. RESULTS: Overall, 396 randomized patients completed the trial: 199 in the citrate group and 197 in the heparin group. There was no significant difference in baseline characteristics between groups. The duration of event-free survival of the first non-tunneled hemodialysis catheter was not significantly different between groups: 7 days (IQR 3-10) in the citrate group and 5 days (IQR 3-11) in the heparin group (p = 0.51). Rates of catheter thrombosis, CRBSI, and adverse events were not statistically different between groups. CONCLUSIONS: In critically ill patients, there was no significant difference in the duration of event-free survival of the first non-tunneled hemodialysis catheter between trisodium citrate 4% and heparin as a locking solution. Catheter thrombosis, catheter-related infection, and adverse events were not statistically different between the two groups. Trial registration Registered with Clinicaltrials.gov under the number NCT01962116. Registered 14 October 2013.

Adhering to the procalcitonin algorithm allows antibiotic therapy to be shortened in patients with ventilator-associated pneumonia.

PURPOSE: Ventilator-associated pneumonia (VAP) increases exposure to antibiotics. Physicians are however reluctant to shorten treatment, arguing this could lead to failures and worse outcome. Monitoring procalcitonin (PCT) has proven effective for decreasing exposure to antibiotics in randomized controlled trials, but additional "real-life" studies are needed. MATERIALS AND METHODS: All patients with VAP in whom ABT was stopped before death or discharge were included in this 5-year prospective cohort study. Patients in whom ABT was stopped in accordance with the algorithm ("PCT-guided" group: ABT withdrawal strongly encouraged if PCT < 0.5 ng/mL or < 80% peak value) were compared to those with ABT continuation despite PCT decrease ("not PCT-guided" group). The primary endpoint was ABT duration. The secondary endpoint was unfavorable VAP outcome (i.e. death or relapse). RESULTS: We included 157 of the 316 patients with microbiologically-proven VAP. The algorithm was overruled in 81 patients (51.6%). ABT duration was significantly longer in these patients than in the PCT-guided group (9.5 vs. 8.0 days; p = .02), although baseline and VAP characteristics did not differ. The rate of unfavorable outcomes was comparable (46.9% vs. 51.3%; p = .69). CONCLUSIONS: PCT-guided ABT adherence appears safe for patients with VAP and is likely to reduce exposure to antibiotics.

Brief summary of French guidelines for the prevention, diagnosis and treatment of hospital-acquired pneumonia in ICU.

BACKGROUND: The French Society of Anaesthesia and Intensive Care Medicine and the French Society of Intensive Care edited guidelines focused on hospital-acquired pneumonia (HAP) in intensive care unit. The goal of 16 French-speaking experts was to produce a framework enabling an easier decision-making process for intensivists. RESULTS: The guidelines were related to 3 specific areas related to HAP (prevention, diagnosis and treatment) in 4 identified patient populations (COPD, neutropenia, post-operative and paediatric). The literature analysis and the formulation of the guidelines were conducted according to the Grade of Recommendation Assessment, Development and Evaluation methodology. An extensive literature research over the last 10 years was conducted based on publications indexed in PubMed™ and Cochrane™ databases. CONCLUSIONS: HAP should be prevented by a standardised multimodal approach and the use of selective digestive decontamination in units where multidrug-resistant bacteria prevalence was below 20%. Diagnosis relies on clinical assessment and microbiological findings. Monotherapy, in the absence of risk factors for multidrug-resistant bacteria, non-fermenting Gram-negative bacilli and/or increased mortality (septic shock, organ failure), is strongly recommended. After microbiological documentation, it is recommended to reduce the spectrum and to prefer monotherapy for the antibiotic therapy of HAP, including for non-fermenting Gram-negative bacilli.

Timing of Renal-Replacement Therapy in Patients with Acute Kidney Injury and Sepsis.

BACKGROUND: Acute kidney injury is the most frequent complication in patients with septic shock and is an independent risk factor for death. Although renal-replacement therapy is the standard of care for severe acute kidney injury, the ideal time for initiation remains controversial. METHODS: In a multicenter, randomized, controlled trial, we assigned patients with early-stage septic shock who had severe acute kidney injury at the failure stage of the risk, injury, failure, loss, and end-stage kidney disease (RIFLE) classification system but without life-threatening complications related to acute kidney injury to receive renal-replacement therapy either within 12 hours after documentation of failure-stage acute kidney injury (early strategy) or after a delay of 48 hours if renal recovery had not occurred (delayed strategy). The failure stage of the RIFLE classification system is characterized by a serum creatinine level 3 times the baseline level (or ≥4 mg per deciliter with a rapid increase of ≥0.5 mg per deciliter), urine output less than 0.3 ml per kilogram of body weight per hour for 24 hours or longer, or anuria for at least 12 hours. The primary outcome was death at 90 days. RESULTS: The trial was stopped early for futility after the second planned interim analysis. A total of 488 patients underwent randomization; there were no significant between-group differences in the characteristics at baseline. Among the 477 patients for whom follow-up data at 90 days were available, 58% of the patients in the early-strategy group (138 of 239 patients) and 54% in the delayed-strategy group (128 of 238 patients) had died (P=0.38). In the delayed-strategy group, 38% (93 patients) did not receive renal-replacement therapy. Criteria for emergency renal-replacement therapy were met in 17% of the patients in the delayed-strategy group (41 patients). CONCLUSIONS: Among patients with septic shock who had severe acute kidney injury, there was no significant difference in overall mortality at 90 days between patients who were assigned to an early strategy for the initiation of renal-replacement therapy and those who were assigned to a delayed strategy. (Funded by the French Ministry of Health; IDEAL-ICU ClinicalTrials.gov number, NCT01682590 .).

Hospital-acquired pneumonia in ICU.

The French Society of Anesthesia and Intensive Care Medicine and the French Society of Intensive Care edited guidelines focused on hospital-acquired pneumonia (HAP) in intensive care unit (ICU). The goal of 16 French-speaking experts was to produce a framework enabling an easier decision-making process for intensivists. The guidelines were related to 3 specific areas related to HAP (prevention, diagnosis and treatment) in 4 identified patient populations (COPD, neutropenia, postoperative and pediatric). The literature analysis and the formulation of the guidelines were conducted according to the Grade of Recommendation Assessment, Development and Evaluation methodology. An extensive literature research over the last 10 years was conducted based on publications indexed in PubMed™ and Cochrane™ databases. HAP should be prevented by a standardized multimodal approach and the use of selective digestive decontamination in units where multidrug-resistant bacteria prevalence was below 20%. Diagnosis relies on clinical assessment and microbiological findings. Monotherapy, in the absence of risk factors for multidrug-resistant bacteria, non-fermenting Gram negative bacilli and/or increased mortality (septic shock, organ failure), is strongly recommended. After microbiological documentation, it is recommended to reduce the spectrum and to prefer monotherapy for the antibiotic therapy of HAP, including for non-fermenting Gram-negative bacilli.

Linezolid and atorvastatin impact on pneumonia caused by Staphyloccocus aureus in rabbits with or without mechanical ventilation.

Pneumonia may involve methicillin-resistant Staphylococcus aureus (MRSA), with elevated rates of antibiotics failure. The present study aimed to assess the effect of statins given prior to pneumonia development. Spontaneously breathing (SB) or mechanically ventilated (MV) rabbits with pneumonia received atorvastatin alone, linezolid (LNZ) alone, or a combination of both (n = 5 in each group). Spontaneously breathing and MV untreated infected animals (n = 11 in each group), as well as uninfected animals (n = 5 in each group) were used as controls. Microbiological features and inflammation were evaluated. Data are presented as medians (interquartile range). Linezolid alone tended to reduce pulmonary MRSA load in both SB and MV rabbits, but failed to prevent bacteremia (59%) in the latter. Linezolid alone dampened TNF-α lung production in both SB and MV rabbits (e.g., 2226 [789] vs. 11478 [10251] pg/g; p = 0.022). Statins alone did the same in both SB and MV animals (e.g., 2040 [133]; p = 0.016), and dampened systemic inflammation in the latter, possibly through TLR2 down-regulation within the lung. However, the combination of LNZ and statin led to an increased rate of bacteremia in MV animals up to 75%. Statins provide an anti-inflammatory effect in rabbits with MRSA pneumonia, especially in MV ones. However, dampening the systemic inflammatory response with statins could impede blood defenses against MRSA.

Mr-Proadm Elevation Upon Icu Admission Predicts the Outcome of Septic Patients and is Correlated with Upcoming Fluid Overload.

BACKGROUND: Among septic patients admitted to the intensive care unit (ICU), early recognition of those with the highest risk of death is of paramount importance. We evaluated the prognostic value of Procalcitonin (PCT), mid regional-proadrenomedullin (MR-proADM), copeptine and CT-proendothelin 1 (CT-ProET 1) concentrations. METHODS: This was a prospective cohort study, which included 173 septic patient admitted to one ICU. Blood samples for biomarker measurements were obtained upon admission and on day 5. The predictive value of each biomarker regarding the risk of death at day 28 was assessed. The fluid balance was evaluated from admission to day 5. RESULTS: All cause ICU mortality was 36.4%. All the biomarkers except CT-ProET-1 were significantly more elevated in the non-survivors than in the survivors upon day 1. This was especially true for MR-proADM (8.6 [5.9] vs. 4.4 [3.9] nmol/L; P < 0.0001) and for the CT-proET-1/MR-proADM ratio (52.9 [22.4] vs. 31.3 [26.6] arbitrary units; P < 0.0001). The best AUROCC values on day 1 were obtained with MR-ProADM and the CT-proET-1/MR-proADM ratio as well (0.75 [0.67-0.85] and 0.82 [0.75-0.89]; 95% CI, respectively). An improved accuracy was achieved on day 5. Moreover, MR-ProADM baseline levels and fluid balance over the 5-day period following ICU admission were strongly correlated (Rho = 0.41; P < 0.001). CONCLUSIONS: In patients admitted to the ICU with sepsis, MR-ProADM on admission was the best predictor of short-term clinical outcome if compared with others. This could be related to its ability to predict fluid sequestration.

Mechanical Ventilation Alters the Development of Staphylococcus aureus Pneumonia in Rabbit.

Ventilator-associated pneumonia (VAP) is common during mechanical ventilation (MV). Beside obvious deleterious effects on muco-ciliary clearance, MV could adversely shift the host immune response towards a pro-inflammatory pattern through toll-like receptor (TLRs) up-regulation. We tested this hypothesis in a rabbit model of Staphylococcus aureus VAP. Pneumonia was caused by airway challenge with S. aureus, in either spontaneously breathing (SB) or MV rabbits (n = 13 and 17, respectively). Pneumonia assessment regarding pulmonary and systemic bacterial burden, as well as inflammatory response was done 8 and 24 hours after S. aureus challenge. In addition, ex vivo stimulations of whole blood taken from SB or MV rabbits (n = 7 and 5, respectively) with TLR2 agonist or heat-killed S. aureus were performed. Data were expressed as mean±standard deviation. After 8 hours of infection, lung injury was more severe in MV animals (1.40±0.33 versus [vs] 2.40±0.55, p = 0.007), along with greater bacterial concentrations (6.13±0.63 vs. 4.96±1.31 colony forming units/gram, p = 0.002). Interleukin (IL)-8 and tumor necrosis factor (TNF)-αserum concentrations reached higher levels in MV animals (p = 0.010). Whole blood obtained from MV animals released larger amounts of cytokines if stimulated with TLR2 agonist or heat-killed S. aureus (e.g., TNF-α: 1656±166 vs. 1005±89; p = 0.014). Moreover, MV induced TLR2 overexpression in both lung and spleen tissue. MV hastened tissue injury, impaired lung bacterial clearance, and promoted a systemic inflammatory response, maybe through TLR2 overexpression.

Significance of Prior Digestive Colonization With Extended-Spectrum ß-Lactamase-Producing Enterobacteriaceae in Patients With Ventilator-Associated Pneumonia.

OBJECTIVES: Ventilator-associated pneumonia is frequent in ICUs. Extended-spectrum ß-lactamase-producing Enterobacteriaceae are difficult-to-treat pathogens likely to cause ventilator-associated pneumonia. We sought to assess the interest of screening for extended-spectrum ß-lactamase-producing Enterobacteriaceae rectal carriage as a way to predict their involvement in ventilator-associated pneumonia. DESIGN: A retrospective cohort study of patients with suspected ventilator-associated pneumonia in a medical ICU was conducted. PATIENTS: Every patient admitted between January 2006 and August 2013 was eligible if subjected to mechanical ventilation for more than 48 hours. Each patient with suspected ventilator-associated pneumonia was included in the cohort. Active surveillance culture for extended-spectrum ß-lactamase-producing Enterobacteriaceae detection was routinely performed in all patients at admission and then weekly throughout the study period. Extended-spectrum ß-lactamase colonization was defined by the isolation of at least one extended-spectrum ß-lactamase-producing Enterobacteriaceae from rectal swab culture. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Among 587 patients with suspected ventilator-associated pneumonia, 40 (6.8%) were colonized with extended-spectrum ß-lactamase-producing Enterobacteriaceae prior to the development of pneumonia. Over the study period, 20 patients (3.4%) had ventilator-associated pneumonia caused by extended-spectrum ß-lactamase-producing Enterobacteriaceae; of whom, 17 were previously detected as being colonized with extended-spectrum ß-lactamase-producing Enterobacteriaceae. Sensitivity and specificity of prior extended-spectrum ß-lactamase-producing Enterobacteriaceae colonization as a predictor of extended-spectrum ß-lactamase-producing Enterobacteriaceae involvement in ventilator-associated pneumonia were 85.0% and 95.7%, respectively. The positive and negative predictive values were 41.5% and 99.4%, respectively. The positive likelihood ratio was 19.8. CONCLUSIONS: Screening for extended-spectrum ß-lactamase-producing Enterobacteriaceae digestive colonization by weekly active surveillance cultures could reliably exclude the risk of the involvement of such pathogens in patients with ventilator-associated pneumonia in low-prevalence area.

Very high volume hemofiltration with the Cascade system in septic shock patients.

PURPOSE: We compared hemodynamic and biological effects of the Cascade system, which uses very high volume hemofiltration (HVHF) (120 mL kg(-1) h(-1)), with those of usual care in patients with septic shock. METHODS: Multicenter, prospective, randomized, open-label trial in three intensive care units (ICU). Adults with septic shock with administration of epinephrine/norepinephrine were eligible. Patients were randomized to usual care plus HVHF (Cascade group), or usual care alone (control group). Primary end point was the number of catecholamine-free days up to 28 days after randomization. Secondary end points were number of days free of mechanical ventilation, renal replacement therapy (RRT) or ICU up to 90 days, and 7-, 28-, and 90-day mortality. RESULTS: We included 60 patients (29 Cascade, 31 usual care). Baseline characteristics were comparable. Median number of catecholamine-free days was 22 [IQR 11-23] vs 20 [0-25] for Cascade vs control; there was no significant difference even after adjustment. There was no significant difference in number of mechanical ventilation-free days or ICU requirement. Median number of RRT-free days was 85 [46-90] vs 74 [0-90] for Cascade vs control groups, p = 0.42. By multivariate analysis, the number of RRT-free days was significantly higher in the Cascade group (up to 25 days higher after adjustment). There was no difference in mortality at 7, 28, or 90 days. CONCLUSION: Very HVHF using the Cascade system can safely be used in patients presenting with septic shock, but it was not associated with a reduction in the need for catecholamines during the first 28 days.

Pulse Wave Transit Time Measurements of Cardiac Output in Septic Shock Patients: A Comparison of the Estimated Continuous Cardiac Output System with Transthoracic Echocardiography.

BACKGROUND: We determined reliability of cardiac output (CO) measured by pulse wave transit time cardiac output system (esCCO system; COesCCO) vs transthoracic echocardiography (COTTE) in mechanically ventilated patients in the early phase of septic shock. A secondary objective was to assess ability of esCCO to detect change in CO after fluid infusion. METHODS: Mechanically ventilated patients admitted to the ICU, aged >18 years, in sinus rhythm, in the early phase of septic shock were prospectively included. We performed fluid infusion of 500 ml of crystalloid solution over 20 minutes and recorded CO by EsCCO and TTE immediately before (T0) and 5 minutes after (T1) fluid administration. Patients were divided into 2 groups (responders and non-responders) according to a threshold of 15% increase in COTTE in response to volume expansion. RESULTS: In total, 25 patients were included, average 64±15 years, 15 (60%) were men. Average SAPSII and SOFA scores were 55±21.3 and 13±2, respectively. ICU mortality was 36%. Mean cardiac output at T0 was 5.8±1.35 L/min by esCCO and 5.27±1.17 L/min by COTTE. At T1, respective values were 6.63 ± 1.57 L/min for esCCO and 6.10±1.29 L/min for COTTE. Overall, 12 patients were classified as responders, 13 as non-responders by the reference method. A threshold of 11% increase in COesCCO was found to discriminate responders from non-responders with a sensitivity of 83% (95% CI, 0.52-0.98) and a specificity of 77% (95% CI, 0.46-0.95). CONCLUSION: We show strong correlation esCCO and echocardiography for measuring CO, and change in CO after fluid infusion in ICU patients.

Incidence and Predictors of New-Onset Atrial Fibrillation in Septic Shock Patients in a Medical ICU: Data from 7-Day Holter ECG Monitoring.

PURPOSE: We investigated incidence, risk factors for new-onset atrial fibrillation (NAF), and prognostic impact during septic shock in medical Intensive Care Unit (ICU) patients. METHODS: Prospective, observational study in a university hospital. Consecutive patients from 03/2011 to 05/2013 with septic shock were eligible. Exclusion criteria were age <18 years, history of AF, transfer with prior septic shock. Included patients were equipped with long-duration (7 days) Holter ECG monitoring. NAF was defined as an AF episode lasting >30 seconds. Patient characteristics, infection criteria, cardiovascular parameters, severity of illness, support therapies were recorded. RESULTS: Among 66 patients, 29(44%) developed NAF; 10 (34%) would not have been diagnosed without Holter ECG monitoring. NAF patients were older, with more markers of heart failure (troponin and NT-pro-BNP), lower left ventricular ejection fraction (LVEF), longer QRS duration and more nonsustained supra ventricular arrhythmias (<30s) on day 1 than patients who maintained sinus rhythm. By multivariate analysis, age (OR: 1.06; p = 0.01) and LVEF<45% (OR: 13.01, p = 0.03) were associated with NAF. NAF did not predict 28 or 90 day mortality. CONCLUSIONS: NAF is common, especially in older patients, and is associated with low ejection fraction. We did not find NAF to be independently associated with higher mortality.

Comparison of heparin to citrate as a catheter locking solution for non-tunneled central venous hemodialysis catheters in patients requiring renal replacement therapy for acute renal failure (VERROU-REA study): study protocol for a randomized controlled trial.

BACKGROUND: The incidence of acute kidney injury (AKI) is estimated at 10 to 20% in patients admitted to intensive care units (ICU) and often requires renal replacement therapy (RRT). ICU mortality in AKI patients can exceed 50%. Venous catheters are the preferred vascular access method for AKI patients requiring RRT, but carry a risk of catheter thrombosis or infection. Catheter lock solutions are commonly used to prevent such complications. Heparin and citrate locks are both widely used for tunneled, long-term catheters, but few studies have compared citrate versus heparin for patients with short-term, non-tunneled catheters. We aim to compare citrate 4% catheter lock solution versus heparin in terms of event-free survival of the first non-tunneled hemodialysis catheter inserted in ICU patients with AKI requiring RRT. Secondary objectives are the rate of fibrinolysis, incidence of catheter thrombosis and catheter-related infection per 1,000 catheter days, length of stay in ICU and in-hospital and 28-day mortality. METHODS/DESIGN: The VERROU-REA study is a randomized, prospective, multicenter, double-blind, parallel-group, controlled superiority study carried out in the medical, surgical and nephrological ICUs of two large university hospitals in eastern France. A catheter lock solution composed of trisodium citrate at 4% will be compared to unfractionated heparin at a concentration of 5,000 IU/mL. All consecutive adult patients with AKI requiring extracorporeal RRT, and in whom a first non-tunneled catheter is to be inserted by the jugular or femoral approach, will be eligible. Catheters inserted by the subclavian approach, patients with acute liver failure, thrombopenia or contraindication to systemic anticoagulation will be excluded. Patients will be followed up daily in accordance with standard practices for RRT until death or discharge. DISCUSSION: Data is scarce regarding the use of non-tunneled catheters in the ICU setting in patients with AKI. This study will provide an evidence base for recommendations regarding the use of anticoagulant catheter locks for the prevention of dysfunction in non-tunneled hemodialysis catheters in patients with AKI in critical or intensive care. TRIAL REGISTRATION: Registered with Clinicaltrials.gov (registration number: NCT01962116) on 27 August 2013.

Impact on mortality of the timing of renal replacement therapy in patients with severe acute kidney injury in septic shock: the IDEAL-ICU study (initiation of dialysis early versus delayed in the intensive care unit): study protocol for a randomized controlled trial.

BACKGROUND: One of the most dreaded complications of septic shock is acute kidney injury. It occurs in around 50% of patients, with a mortality rate of about 60% at 3 months. There is no consensus on the optimal time to initiate renal replacement therapy. Retrospective and observational studies suggest that early implementation of renal replacement therapy could improve the prognosis for these patients. METHODS/DESIGN: This protocol summarizes the rationale and design of a randomized, controlled, multicenter trial investigating the effect of early versus delayed renal replacement therapy in patients with severe acute kidney injury in early septic shock. In total, 864 critically ill adults with septic shock and evidence of acute kidney injury, defined as the failure stage of the RIFLE classification, will be enrolled. The primary outcome is mortality at 90 days. Secondary outcomes include safety, number of days free of mechanical ventilation, number of days free of renal replacement therapy, intensive care length of stay, in-hospital length of stay, quality of life as evaluated by the EQ-5D and renal replacement therapy dependence at hospital discharge. The primary analysis will be intention to treat. Recruitment started in March 2012 and will be completed by March 2015. DISCUSSION: This protocol for a randomized controlled study investigating the impact of the timing of renal replacement therapy initiation should provide an answer to a key question for the management of patients with acute kidney injury in the context of septic shock, for whom the mortality rate remains close to 60% despite improved understanding of physiopathology and recent therapeutic advances. TRIAL REGISTRATION: ClinicalTrials.gov identifier NCT01682590, registered on 10 September 2012.

Empirical antifungal therapy with an echinocandin in critically-ill patients: prospective evaluation of a pragmatic Candida score-based strategy in one medical ICU.

BACKGROUND: Invasive candidiasis (IC) is a life-threatening ICU-acquired infection. A strong correlation between time to antifungal therapy (AFT) administration and outcome has been established. Empirical therapy benefit should be balanced with the risk of echinocandin overuse. We assessed therefore a decision rule that aimed at guiding empirical therapy. METHODS: A 45-month prospective cohort study in a teaching medical ICU. All of the patients with suspected IC (uncontrolled sepsis despite broad spectrum antibiotics without any bacterial proven infection in patients with Candida score ≥ 3 points including multifocal Candida sp. colonization) were eligible. The primary endpoint was proven IC diagnosis (i.e., candidemia) following treatment onset. Timing of AFT administration was also investigated in those latter patients. Antifungal therapy step-down and discontinuation was done according to international guidelines in patients with candidemia. Otherwise, echinocandin discontinuation was encouraged in patients without proven IC, excepting when a clinical improvement was achieved without any other explanation that antifungals initiation (i.e., probable IC). In addition, a survival multivariate analysis using a Cox model was conducted. RESULTS: Fifty-one patients were given an echinocandin with respect to our decision rule. Among them, candidemia was diagnosed thereafter in 9 patients. Over the same period, antifungal therapy was triggered by candidemia announcement (i.e., definite therapy) in 12 patients who did not fulfill criteria for empirical therapy before. Time elapsed from candidemia onset to echinocandin therapy initiation was shortened (0.4 [0.5] vs. 2.4 [2.8] hours; p = 0.04) when it was given empirically. In addition, 18 patients clinically improved under empirical antifungal therapy without any obvious other explanation, despite IC remained unproven. Moreover, echinocandin exposure duration was independently related to survival in those patients. Over the same period, our predefined criteria for empirical therapy were overruled in 55 cases. None of them develop IC thereafter. Finally, Our decision rule allowed IC early recognition of proven/probable IC with sensitivity, specificity, positive and negative predictive value of 69.2%, 82.1%, 69.2% and 82.1%, respectively. CONCLUSION: Implementation of pragmatic guidelines for empirical AFT based on CS and fungal colonization assessment could be useful in selecting patients who really benefit from an echinocandin.

Impact of prior statin therapy on the outcome of patients with suspected ventilator-associated pneumonia: an observational study.

INTRODUCTION: Ventilator-associated pneumonia (VAP) is the most commonly acquired infection in intensive care units (ICU). Its outcome is related, at least in part, to the host's response. Statins have anti-inflammatory effects and may thus improve the outcome. We aimed to assess the impact of prior statin use in the setting of VAP. METHODS: A six-year cohort study was conducted in a French ICU at a teaching hospital. All of the patients with suspected VAP were included. Baseline characteristics, outcomes, statin exposure, and the description of suspected episodes were collected prospectively. The primary endpoint was 30-day mortality. Patients who were taking statins before admission to the ICU whether or not treatment was continued thereafter ('previous users' group) were compared to those without prior statin therapy ('statin-naive' group). A survival analysis using a Cox model was conducted in the whole cohort and in the subgroup of prior statin users. RESULTS: Among the 349 patients included, 93 (26.6%) had taken statins. At baseline, these patients were at higher risk of complications than statin-naive ones (for example, older, more likely to be men and to have underlying diseases, greater simplified acute physiology score II (SAPS II)). There was, however, no difference regarding severity at the time VAP was suspected (sequential organ failure assessment (SOFA): 9.0 (4.0 to 16.0) versus 8.0 (4.0 to 17.0); P = 0.11). Nonetheless, 30-day mortality in statin users was not different from that in statin-naive patients (35.5% versus 26.2%, respectively; adjusted hazard ratio (HR) = 1.23 (0.79 to 1.90) 95% confidence interval (CI); P = 0.36). In contrast, after limiting analysis to prior statin users and adjusting for potential confounders, those who continued the treatment had better survival than those who did not (HR = 0.47; (0.22 to 0.97) 95% CI; P = 0.04). CONCLUSIONS: Statin continuation in prior users could provide protective effects in patients with suspected VAP.

A randomized controlled trial of pudendal nerve block for pain relief after episiotomy.

BACKGROUND: Pain from episiotomy or perineal tears during childbirth is associated with significant pain in the postpartum period. We performed this randomized, double-blind, controlled trial to investigate the efficacy of nerve stimulator-guided unilateral pudendal nerve block for pain relief after episiotomy. METHODS: Forty women who gave birth vaginally with mediolateral episiotomy were randomized to receive pudendal nerve block with 15 mL of either ropivacaine 7.5 mg/mL (pudendal group) or normal saline (control group) after repair of the episiotomy. Episiotomy pain was assessed with a visual analog scale at rest at 3, 6, 12, 24, and 48 h postepisiotomy and during activities (walking and sitting). Breakthrough pain (visual analog scale >30 mm) was treated with niflumic acid suppositories 700 mg every 12 h. The primary outcome variables were pain scores at rest and during activities over 48 h postpartum. RESULTS: Demographic and obstetric characteristics were not different between groups. Successful pudendal nerve stimulation was achieved in all patients. Patients in the pudendal group reported significantly lower pain scores at rest than those in the control group at 3, 6, 12, 24, and 48 h after delivery (P < 0.05). They also reported better analgesia while sitting and walking (P < 0.05). Additional analgesia was required by three patients (15%) in the pudendal group versus 17 patients (85%) in the placebo group (P < 0.001). CONCLUSION: This study demonstrates that nerve stimulator-guided unilateral pudendal nerve block with ropivacaine 7.5 mg/mL is associated with decreased pain and need for additional analgesics during the first 48 h postepisiotomy.