Usefulness of Gram stain examination of peritoneal fluid in postoperative peritonitis to guide empirical antibiotherapy.

PURPOSE: In postoperative peritonitis, Gram stain examination (GSE) of peritoneal fluid has been proposed as a guide for the prescription of glycopeptides and antifungal therapy in empirical antibiotherapy. No data support this approach for Gram-positive cocci. We aimed to evaluate the performance of GSE in predicting the results of the culture of peritoneal fluid. METHODS: In this retrospective single-center study, concordance between GSE and culture of peritoneal fluid was assessed for different types of microorganisms. Factors associated with concordance of the two tests were evaluated in the subpopulation of Gram-positive cocci peritonitis. RESULTS: Among the 152 episodes, the GSE was negative in 57 cases. The negative predictive value and the positive predictive value were 41% and 87% for Gram-positive cocci (GPC), 31% and 86% for Gram-negative bacilli, and 78% and 94% for fungi. GSE is not a reliable guide for the choice of empirical antibiotherapy and cannot reliably rule out the presence of GPC at culture. If we aim to achieve a high rate of adequacy, the systematic use of glycopeptide in the empirical antibiotherapy may be considered. CONCLUSION: GSE shows poor performance to predict the results of culture of peritoneal fluid in postoperative peritonitis. Avoiding covering resistant GPC cannot be based on the result of GSE.

Pulmonary Effects of Adjusting Tidal Volume to Actual or Ideal Body Weight in Ventilated Obese Mice.

Obese patients could be more susceptible to mechanical ventilation (MV)-induced lung injury than non-obese patients due to weight-dependent changes in lung properties. The aim of this study was therefore to evaluate the pulmonary effects of 2 hours low VT MV in a diet-induced obese mice model, with VT calculated on either the actual body weight (VTaw) or the ideal body weight (VTiw) . First, we hypothesized that a MV with VTaw would be associated with altered lung mechanics and an increased lung inflammation. Second, we hypothesised that a MV with a VTiw would preserve lung mechanics and limit lung inflammation. We analyzed lung mechanics and inflammation using bronchoalveolar lavage (BAL) cell counts, flow cytometry tissue analysis and histology. Lung mechanics and inflammation were comparable in control and obese mice receiving VTiw. By contrast, obese mice receiving VTaw had significantly more alterations in lung mechanics, BAL cellularity and lung influx of monocytes as compared to control mice. Their monocyte expression of Gr1 and CD62L was also increased. Alveolar neutrophil infiltration was significantly increased in all obese mice as compared to controls. In conclusion, our findings suggest that protective MV with a VTaw is deleterious, with a marked alteration in lung mechanics and associated lung inflammation as compared to lean mice. With VTiw, lung mechanics and inflammation were close to that of control mice, except for an increased alveolar infiltrate of polymorphonuclear neutrophils. This inflammation might be attenuated by a blunted recruitment of inflammatory cells associated with obesity.

Morbidity and mortality related to pneumonia and TRACHEOBRONCHITIS in ICU after lung transplantation.

BACKGROUND: Bacterial respiratory infections (BRI) are major complications contributing to increased morbidity and mortality after lung transplantation (LT). This study analyzed epidemiology and outcome of 175 consecutive patients developing BRI in ICU after LT between 2006 and 2012. METHODS: Three situations were described: colonization determined in donors and recipients, pneumonia and tracheobronchitis during the first 28 postoperative days. Severity score, demographic, bacteriologic and outcome data were collected. RESULTS: 26% of donors and 31% of recipients were colonized. 92% of recipients developed BRI, including at least one episode of pneumonia in 19% of recipients. Only 21% of recipients developed BRI with an organism cultured from the donor's samples, while 40% of recipients developed BRI with their own bacteria cultured before LT. Purulent sputum appears to be an important factor to discriminate tracheobronchitis from pneumonia. When compared to patients with tracheobronchitis, those with pneumonia had longer durations of mechanical ventilation (13 [3-27] vs 3 [29], p = 0.0005) and ICU stay (24 [16-34] vs 14 [9-22], p = 0.002). Pneumonia was associated with higher 28-day (11 (32%) vs 9 (7%), p = 0.0004) and one-year mortality rates (21 (61%) vs 24 (19%), p ≤ 0.0001). CONCLUSIONS: These data confirm the high frequency of BRI right from the early postoperative period and the poor prognosis of pneumonia after LT.

Impact of connecting continuous renal replacement therapy to the extracorporeal membrane oxygenation circuit.

PURPOSE: Continuous veno-venous haemofiltration (CVVH) directly connected to extracorporeal membrane oxygenation (ECMO) may ensure better blood flow and allow prolonged circuit life. The objective of this study was to assess circuit life of CVVH connected to ECMO and to a dialysis catheter. MATERIALS AND METHODS: In this prospective observational study, patients receiving CVVH via ECMO were compared to time-matched patients receiving CVVH via a conventional dialysis catheter. CVVH circuit life and the safety and efficacy of the two CVVH procedures were analysed. Time to event was estimated using Kaplan-Meier analysis and compared using the log-rank test. RESULTS: Seventeen patients were included in each group, with 43 sessions in the ECMO group and 56 sessions in the DC group. Median CVVH circuit life was 48 [21-72] vs 20 [6-39] hours in the ECMO and DC groups, respectively (relative risk of termination of the session: 2.4, 95% CI [1.41-3.9], log rank P=0.0009). CVVH blood flow was higher in the ECMO group. Despite higher anticoagulant doses in the catheter group, the circuit clotting rate was lower in the ECMO group. Effluent volume was slightly higher in the ECMO group (39ml/kg/h [33-47] vs 34ml/kg/h [32-39]), but with no biological impact. CVVH via ECMO was well tolerated with no major drawbacks. CONCLUSIONS: In patients requiring ECMO, CVVH connected to ECMO instead of DC could be proposed as an alternative approach, allowing more stable blood flow and prolonged CVVH circuit life.

Evaluation of Cardiac Index and Extravascular Lung Water After Single-Lung Transplantation Using the Transpulmonary Thermodilution Technique by the PiCCO2 Device.

OBJECTIVES: First evaluation of the transpulmonary thermodilution technique by the PiCCO2 device to assess cardiac index and pulmonary edema during the postoperative course after single-lung transplantation. DESIGN: Prospective observational study. SETTINGS: Intensive care unit, university hospital (single center). PARTICIPANTS: Single-lung transplant patients. INTERVENTIONS: The authors compared cardiac index measured by PiCCO2 and pulmonary artery catheter and assessed pulmonary edema using extravascular lung water index and pulmonary vascular permeability index measured by PiCCO2. MEASUREMENTS AND MAIN RESULTS: A Bland-Altman method was used to compare cardiac index measured by PiCCO2 and pulmonary artery catheter. Extravascular lung water index and pulmonary vascular permeability index were compared according to the PaO2/FiO2 ratio with a threshold value of 150 mmHg. Ten single-lung transplant patients were included. Cardiac index measured by PiCCO2 and pulmonary artery catheter were 3.3 L/min/m2 (2.9-3.6) and 2.5 L/min/m2 (2.2-3.0). Bias for cardiac index was 0.71 L/min/m2 (-0.03; 1.44) and limit of agreements were -0.03 and 1.44 L/min/m2. Extravascular lung water index was 12 mL/kg (11-16) and pulmonary vascular permeability index was 2.3 (2.0-3.1), consistent with pulmonary edema. Extravascular lung water index was higher in the group of PaO2/FiO2 ratio ≤150 mmHg compared with the group of PaO2/FiO2 ratio >150 mmHg (17 v 12 mL/kg, p = 0.04), whereas pulmonary vascular permeability index only tended to be higher (3.1 v 2.1, p = 0.06). CONCLUSION: PiCCO2 device systematically overestimated cardiac index compared with pulmonary artery catheter. However, it might be useful to assess pulmonary edema in acute respiratory failure after single-lung transplantation.

CRRT Connected to ECMO: Managing High Pressures.

Metabolic disorders and fluid overload are indications of continuous renal replacement therapy (CRRT) including continuous venovenous hemofiltration in patients on extracorporeal membrane oxygenation (ECMO). Direct connection of CRRT machine to the ECMO circuit provides many advantages. Nevertheless, because pressures in CRRT lines relate to ECMO blood flow, high ECMO blood flow may be associated with high pressures in CRRT lines. Thus, management of CRRT pressure lines becomes challenging. We evaluated a protocol for managing high CRRT pressures. Connections were performed according to a standardized protocol to maintain CRRT lines in the correct pressure ranges without modifying ECMO settings or inhibiting pressure alarms. To achieve this goal, the way of connecting of CRRT lines was adapted following a standardized protocol. Connection was first attempted between pump and oxygenator in the 12 patients. In five cases, high pressures in CRRT lines were successfully managed by changing the connection segment. Continuous renal replacement therapy parameters were within target levels and reduction of serum creatinine was 37%. In conclusion, management of high pressures in CRRT lines induced by ECMO could be achieved without modifying ECMO blood flow or inhibiting CRRT alarms. Iterative stops were avoided allowing efficient procedures.

Characteristics and outcomes of anti-infective de-escalation during health care-associated intra-abdominal infections.

BACKGROUND: De-escalation is strongly recommended for antibiotic stewardship. No studies have addressed this issue in the context of health care-associated intra-abdominal infections (HCIAI). We analyzed the factors that could interfere with this process and their clinical consequences in intensive care unit (ICU) patients with HCIAI. METHODS: All consecutive patients admitted for the management of HCIAI who survived more than 3 days following their diagnosis, who remained in the ICU for more than 3 days, and who did not undergo early reoperation during the first 3 days were analyzed prospectively in an observational, single-center study in a tertiary care university hospital. RESULTS: Overall, 311 patients with HCIAI were admitted to the ICU. De-escalation was applied in 110 patients (53%), and no de-escalation was reported in 96 patients (47%) (escalation in 65 [32%] and unchanged regimen in 31 [15%]). Lower proportions of Enterococcus faecium, nonfermenting Gram-negative bacilli (NFGNB), and multidrug-resistant (MDR) strains were cultured in the de-escalation group. No clinical difference was observed at day 7 between patients who were de-escalated and those who were not. Determinants of de-escalation in multivariate analysis were adequate empiric therapy (OR 9.60, 95% CI 4.02-22.97) and empiric use of vancomycin (OR 3.39, 95% CI 1.46-7.87), carbapenems (OR 2.64, 95% CI 1.01-6.91), and aminoglycosides (OR 2.31 95% CI 1.08-4.94). The presence of NFGNB (OR 0.28, 95% CI 0.09-0.89) and the presence of MDR bacteria (OR 0.21, 95% CI 0.09-0.52) were risk factors for non-de-escalation. De-escalation did not change the overall duration of therapy. The risk factors for death at day 28 were presence of fungi (HR 2.64, 95% CI 1.34-5.17), Sequential Organ Failure Assessment score on admission (HR 1.29, 95% CI 1.16-1.42), and age (HR 1.03, 95% CI 1.01-1.05). The survival rate expressed by a Kaplan-Meier curve was similar between groups (log-rank test p value 0.176). CONCLUSIONS: De-escalation is a feasible option in patients with polymicrobial infections such as HCIAI, but MDR organisms and NFGNB limit its implementation.

Dynamic changes of microbial flora and therapeutic consequences in persistent peritonitis.

INTRODUCTION: Persistent peritonitis is a frequent complication of secondary peritonitis requiring additional reoperations and antibiotic therapy. This situation raises specific concerns due to microbiological changes in peritoneal samples, especially the emergence of multidrug-resistant (MDR) strains. Although this complication has been extensively studied, the rate and dynamics of MDR strains have rarely been analysed. METHODS: We compared the clinical, microbiological and therapeutic data of consecutive ICU patients admitted for postoperative peritonitis either without subsequent reoperation (n = 122) or who underwent repeated surgery for persistent peritonitis with positive peritoneal fluid cultures (n = 98). Data collected on index surgery for the treatment of postoperative peritonitis were compared between these two groups. In the patients with persistent peritonitis, the data obtained at the first, second and third reoperations were compared with those of index surgery. Risk factors for emergence of MDR strains were assessed. RESULTS: At the time of index surgery, no parameters were able to differentiate patients with or without persistent peritonitis except for increased severity and high proportions of fungal isolates in the persistent peritonitis group. The mean time to reoperation was similar from the first to the third reoperation (range: 5 to 6 days). Septic shock was the main clinical expression of persistent peritonitis. A progressive shift of peritoneal flora was observed with the number of reoperations, comprising extinction of susceptible strains and emergence of 85 MDR strains. The proportion of patients harbouring MDR strains increased from 41% at index surgery, to 49% at the first, 54% at the second (P = 0.037) and 76% at the third reoperation (P = 0.003 versus index surgery). In multivariate analysis, the only risk factor for emergence of MDR strains was time to reoperation (OR 1.19 per day, 95%CI (1.08 to 1.33), P = 0.0006). CONCLUSIONS: Initial severity, presence of Candida in surgical samples and inadequate source control are the major risk factors for persistent peritonitis. Emergence of MDR bacteria is frequent and increases progressively with the number of reoperations. No link was demonstrated between emergence of MDR strains and antibiotic regimens, while source control and its timing appeared to be major determinants of emergence of MDR strains.

Diagnosis and management of the postoperative surgical and medical complications of bariatric surgery.

Perioperative complications following bariatric surgery (BS) have been poorly analysed and their management is not clearly assessed. The associated frequency of ICU admission is difficult to estimate. Among surgical complications, digestive perforations are the most frequent. The most common postoperative complications of sleeve gastrectomy are fistulas, but bleeding on the stapling line is also commonly reported. Complication rates are higher after Roux-en-Y gastric bypass, mainly due to anastomotic leaks. Medical complications are mainly thromboembolic or respiratory complications. All these surgical and medical complications are not easily detected; clinical signs can be atypical or insidious, often resulting in delayed management. Respiratory signs can be predominant and lead erroneously to pulmonary or thromboembolic diseases. Diagnostic criteria are based on minor clinical signs, tachycardia being probably the most frequent one. Lately, complications are revealed by haemodynamic instability, respiratory failure or renal dysfunction and radiographic findings. Management decision according to these abnormal signs is based on a combined multidisciplanary approach including surgical and/or endoscopic procedures and medical care, depending on the nature and severity of the surgical complication. Medical management is based on supportive ICU care of organ dysfunctions, curative anticoagulation if required, nutritional support, and appropriate anti-infective therapy. Pharmacological data are limited in morbidly obese patients and the appropriate doses are debated, especially for anti-infective agents. Complicated BS cases have a poor outcome, probably largely related to delayed diagnosis and reoperation.

Postoperative pneumonia following cardiac surgery in non-ventilated patients versus mechanically ventilated patients: is there any difference?

INTRODUCTION: No studies have compared ventilator-associated pneumonia (VAP) and non-VAP following cardiac surgery (CS). The aim of this study was to assess the incidence, clinical and microbiologic features, treatment characteristics and prognosis of postoperative pneumonia following CS with a special focus on non-VAP. METHODS: This was a retrospective cohort study based on a prospectively collected database. We compared cases of non-VAP and VAP following CS observed between January 2005 and December 2012. Statistical analysis consisted of bivariate and multivariate analysis. RESULTS: A total of 257 (3.5%) of 7,439 consecutive CS patients developed postoperative pneumonia, including 120 (47%) cases of non-VAP. Patients with VAP had more frequent history of congestive heart failure (31% vs. 17%, P = 0.006) and longer duration of cardiopulmonary bypass (105 vs 76 min, P < 0.0001), than patients with non-VAP. No significant differences were observed between the 2 groups in terms of the types of microorganisms isolated with high proportions of Enterobacteriaceae (35%), Pseudomonas aeruginosa (20.2%) and Haemophilus spp (20.2%), except for a lower proportion of Methicillin-susceptible S. aureus in the non-VAP group (3.2% vs 7.9%, P = 0.03). In the intensive care unit, patients with non-VAP had lower sequential organ failure assessment scores than patients with VAP (8 ± 3 versus 9 ± 3, P = 0.004). On multivariate analysis, in-hospital mortality was similar in both groups (32% in the non-VAP group and 42% in the VAP group, adjusted Odds Ratio (aOR): 1.4; 95% confidence intervals (CI): 0.7-2.5; P = 0.34) and appropriate empiric antibiotic therapy was associated with a reduction of in-hospital mortality (aOR: 0.4; 95% CI: 0.2-1; P = 0.05). Piperacillin/tazobactam or imipenem monotherapy constituted appropriate empiric therapy in the two groups, with values reaching 93% and 95% with no differences between VAP and non-VAP cases. CONCLUSIONS: Intensive care patients with VAP are more severely ill than non-VAP patients following CS. Nevertheless, patients with non-VAP and VAP following CS have similar outcomes. This study suggests that the empiric antibiotic regimen in patients with pneumonia following CS should include at least a broad-spectrum antibiotic targeting non-fermenting Gram-negative bacilli, regardless of the type of pneumonia, and targeting S. aureus in VAP patients.

Post-operative kinetics of procalcitonin after lung transplantation.

BACKGROUND: Post-operative infections are a major complication after lung transplantation (LT). Early bacterial pneumonia worsens the prognosis of LT. Procalcitonin (PCT) has been proposed as an early and rapid laboratory marker of infection and sepsis. PCT could be a useful biomarker of pulmonary infection after LT, but the early kinetics of PCT in this setting are unknown. We evaluated the kinetics of PCT and the impact of respiratory tract infection on PCT concentrations. METHODS: Over a 12-month period, PCT concentrations were determined daily in each patient admitted to our ICU for LT. Epidemiologic, clinical, laboratory and outcome data were obtained. A diagnosis of respiratory tract infection was suspected on clinical examination and confirmed by microbiologic culture. RESULTS: Twenty-six consecutive patients were included and 397 blood samples were obtained (13 [range 4 to 66] samples per patient). Plasma PCT reached a peak in the first 24 hours post-transplantation (5.72 [0.11 to 93.8] ng/ml), with a progressive decline over the first 7 post-operative days. Doubling of plasma PCT levels after an initial decrease was significantly associated with respiratory tract infection in transplanted patients (RR = 4.2 95% CI [1.95 to 9.03]). CONCLUSIONS: A non-specific increase in PCT values was observed during the first week post-LT. In combination with microbiologic cultures, PCT assays may be useful after the first post-operative week as an aid in the diagnosis of bacterial pulmonary infection.

Echocardiography to predict tolerance to negative fluid balance in acute respiratory distress syndrome/acute lung injury.

PURPOSE: In acute respiratory distress syndrome (ARDS) and acute lung injury (ALI), a conservative fluid management strategy improves lung function but could jeopardize extrapulmonary organ perfusion. The objective was to evaluate the diagnostic accuracy of echocardiography to predict tolerance of negative fluid balance (NFB) in patients with ARDS/ALI. MATERIALS AND METHODS: A prospective and observational study in an adult intensive care unit of a university hospital was conducted. All hemodynamically stable patients with ARDS/ALI were included. Echocardiography was performed before NFB and again after 24 hours. Tolerance of NFB was evaluated by the presence of hypotension, acute kidney injury, or need for fluid expansion. The 2 patient groups (tolerating and not tolerating NFB) were compared. RESULTS: Forty-five patients were included. Median age (Q1-Q3) was 58 (52-66) years, and the ratio of partial pressure of arterial oxygen to the fraction of inspired oxygen was 205 (163-258) mm Hg. Negative fluid balance was 1950 (1200-2200) mL within 24 hours in the tolerant group. Complications of NFB were observed in 35% cases. After univariate and multivariate logistic regression analyzes, 2 criteria was independently associates with poor tolerance: mitral inflow E wave to early diastolic mitral annulus velocities ratio (E/Ea ratio; odds ratio, 2.02 [1.02-4.02]; P = .04) and weight gain (odds ratio, 1.2 [1.03-1.4]; P = .02). The area under receiver operating characteristic curves was 0.74 for E/Ea and 0.77 for weight gain. CONCLUSIONS: The ratio of E/Ea accurately predicted tolerance of NFB in patients with ARDS/ALI.

Pseudomonas aeruginosa post-operative peritonitis: clinical features, risk factors, and prognosis.

BACKGROUND: Postoperative peritonitis (PP) is associated with a high rate of multi-drug-resistant micro-organisms. The role of Pseudomonas aeruginosa in this condition has never been assessed. We evaluated the risk factors and prognosis for PP caused by P. aeruginosa. METHODS: Patients hospitalized in the intensive care unit (ICU) after re-operation for PP were identified prospectively. Analyses were performed retrospectively. Specific risk factors were investigated by comparing P. aeruginosa PP with PP having other causes. The main outcome endpoint was death in the hospital. RESULTS: We found 55 P. aeruginosa PP among the 349 cases of PP (16%) in the ICU over 14 years. Factors associated with the presence of P. aeruginosa in peritoneal fluid culture were Acute Physiology and Chronic Health Evaluation (APACHE) II score (odds ratio [OR] 1.1; 95% confidence interval [CI] 1.02-1.09; p=0.004) and respiratory failure (OR 2.3; 95% CI 1.26-4.16; p=0.006). These criteria performed poorly in predicting P. aeruginosa PP. Such infections were associated with a higher hospital mortality rate, but not after adjustment for the severity score. Adequate antibiotic therapy comprising two antibiotics effective against P. aeruginosa was associated with a lower mortality rate for P. aeruginosa PP in the ICU. CONCLUSION: The prevalence of P. aeruginosa PP is not high. Risk factors do not allow accurate prediction of the infection. Our data suggest two drugs effective against P. aeruginosa should be considered for treating these infections.

Clinical features and outcome of postoperative peritonitis following bariatric surgery.

BACKGROUND: We assessed the clinical features and outcome of morbidly obese patients admitted to the intensive care unit (ICU) for management of postoperative peritonitis (POP) following bariatric surgery (BS). METHODS: In a prospective, observational, surgical ICU cohort, we compared the clinical features, empiric antibiotic therapy, and prognosis of BS patients with those developing POP after conventional surgery (cPOP). RESULTS: Overall, 49 BS patients were compared to 134 cPOP patients. BS patients were younger (45 ± 10 versus 63 ± 16 years; p < 0.0001), had lower rates of fatal underlying disease (39 vs. 64%; p = 0.002), and the same SOFA score at the time of reoperation (8 ± 4 vs 8 ± 3; p = 0.8) as the cPOP patients. BS patients had higher proportions of Gram-positive cocci (48 vs. 35 %; p = 0.007) and lower proportions of Gram-negative bacilli (33 vs. 44%; p = 0.03), anaerobes (4 vs. 10%; p = 0.04), and multidrug-resistant strains (20 vs. 40%; p = 0.01). Despite higher rates of adequate empiric antibiotic therapy (82 vs. 64%; p = 0.024) and high de-escalation rates (67% in BS cases and 51% in cPOP cases; p = 0.06), BS patients had similar reoperation rates (53 vs. 44%; p = 0.278) and similar mortality rates (24 vs. 32%; p = 0.32) to cPOP patients. In multivariate analysis, none of the risk factors for death were related to BS. CONCLUSIONS: The severity of POP in BS patients resulted in high mortality rates, similar to the results observed in cPOP. Usual empiric antibiotic therapy protocols should be applied to target multidrug-resistant microorganisms, but de-escalation can be performed in most cases.

Differential antibacterial activity against Pseudomonas aeruginosa by carbon monoxide-releasing molecules.

AIMS: Carbon monoxide (CO) delivered in a controlled manner to cells and organisms mediates a variety of pharmacological effects to the extent that CO-releasing molecules (CO-RMs) are being developed for therapeutic purposes. Recently, ruthenium-based CO-RMs have been shown to posses important bactericidal activity. Here we assessed the effect of fast CO releasers containing ruthenium (Ru(CO)(3)Cl(glycinate) [CORM-3] and tricarbonyldichlororuthenium(II) dimer [CORM-2]) and a novel slow manganese-based CO releaser ([Me(4)N][Mn(CO)(4)(thioacetate)(2)] [CORM-371]) on O(2) consumption and growth of Pseudomonas aeruginosa (PAO1). We then compared these effects with the action elicited by sodium boranocarbonate (CORM-A1), which lacks a transition metal but liberates CO with a rate similar to CORM-371. RESULTS: CORM-2, CORM-3, and, to a lesser extent, CORM-371 exerted a significant bactericidal effect and decreased O(2) consumption in PAO1 in vitro. The effect appeared to be independent of reactive oxygen species production, but in the case of metal-containing compounds it was prevented by the thiol donor N-acetylcysteine. In contrast, CORM-A1 was bacteriostatic rather than bactericidal in vitro eliciting only a moderate and transient decrease in O(2) consumption. INNOVATION: None of the tested CO-RMs was toxic to murine macrophages or human fibroblasts at the concentration impairing PA01 growth but only ruthenium-containing CO-RMs showed potential therapeutic properties by increasing the survival of mice infected with PA01. CONCLUSION: CO carriers inhibit bacterial growth and O(2) consumption in vitro, but transition metal carbonyls appear more powerful than compounds spontaneously liberating CO. The nature of the metal in CO-RMs also modulates the anti-bacterial effect, with ruthenium-based CO-RMs being efficacious both in vitro and in vivo.

Extracorporeal membrane oxygenation in 5 patients with bronchial fistula with severe acute lung injury.

PURPOSE: The management of bronchial fistula associated with acute lung injury raises two major concerns: (1) high ventilation pressures are necessary for lung recruitment but detrimental for fistula healing, and (2) adequate lung recruitment is prevented by large air leak. Primary surgical closure of bronchial fistula should be attempted but is rarely successful during mechanical ventilation. We sought to evaluate the efficacy of extracorporeal membrane oxygenation associated with lung-protective ventilation in case of failure of conventional management. DESCRIPTION: Arteriovenous extracorporeal membrane oxygenation was initiated by femorofemoral cannulation. A stepwise increase of extracorporeal membrane oxygenation output and a decrease of mechanical ventilation settings were simultaneously performed, aiming at lung-protective ventilation. EVALUATION: During a 1-year period, this protocol management was used in 5 patients with refractory respiratory failure associated with bronchial fistula after thoracic operations. This strategy allowed fistula healing in 3 patients. CONCLUSIONS: If correctly timed, extracorporeal membrane oxygenation can provide a therapeutic bridge to lung-protective ventilation and allow bronchial fistula healing in case of refractory respiratory failure.

Clinical review: intrapericardial fibrinolysis in management of purulent pericarditis.

Purulent pericarditis (PP) is a potentially life-threatening disease. Reported mortality rates are between 20 and 30%. Constrictive pericarditis occurs over the course of PP in at least 3.5% of cases. The frequency of persistent PP (chronic or recurrent purulent pericardial effusion occurring despite drainage and adequate antibiotherapy) is unknown because this entity was not previously classified as a complication of PP. No consensus exists on the optimal management of PP. Nevertheless, the cornerstone of PP management is complete eradication of the focus of infection. In retrospective studies, compared to simple drainage, systematic pericardiectomy provided a prevention of constrictive pericarditis with better clinical outcome. Because of potential morbidity associated with pericardiectomy, intrapericardial fibrinolysis has been proposed as a less invasive method for prevention of persistent PP and constrictive pericarditis. Experimental data demonstrate that fibrin formation, which occurs during the first week of the disease, is an essential step in the evolution to constrictive pericarditis and persistent PP. We reviewed the literature using the MEDLINE database. We evaluated the clinical efficacy, outcome, and complications of pericardial fibrinolysis. Seventy-four cases of fibrinolysis in PP were analysed. Pericarditis of tuberculous origin were excluded. Among the 40 included cases, only two treated by late fibrinolysis encountered failure requiring pericardiectomy. No patient encountered clinical or echocardiographic features of constriction during follow-up. Only one serious complication was described. Despite the lack of definitive evidence, potential benefits of fibrinolysis as a less invasive alternative to surgery in the management of PP seem promising. Early consideration should be given to fibrinolysis in order to prevent both constrictive and persistent PP. Nevertheless, in case of failure of fibrinolysis, pericardiectomy remains the primary option for complete eradication of infection.

A long-term clinical evaluation of autoflow during assist-controlled ventilation: a randomized controlled trial.

BACKGROUND: Many new mechanical ventilation modes are proposed without any clinical evaluation. "Dual-controlled" modes, such as AutoFlow™, are supposed to improve patient- ventilator interfacing and could lead to fewer alarms. We performed a long-term clinical evaluation of the efficacy and safety of AutoFlow during assist-controlled ventilation, focusing on ventilator alarms. METHODS: Forty-two adult patients, receiving mechanical ventilation for more than 2 days with a Dräger Evita 4 ventilator were randomized to conventional (n = 21) or AutoFlow (n = 21) assist-controlled ventilation. Sedation was given using a nurse-driven protocol. Ventilator-generated alarms were exhaustively recorded from the ventilator logbook with a computer. Daily blood gases and ventilation outcome were recorded. RESULTS: A total of 403 days of mechanical ventilation were studied and 45,022 alarms were recorded over a period of 8074 hours. The course of respiratory rate, minute ventilation, Fio(2), positive end-expiratory pressure, Pao(2)/Fio(2), Paco(2), and pH and doses and duration of sedation did not differ between the 2 groups. Outcome (duration of mechanical ventilation, ventilator-associated pneumonia, course of Sequential Organ Failure Assessment score, or death) was not different between the 2 groups. The number of alarms per hour was lower with AutoFlow assist-controlled ventilation: 3.3 [1.5 to 17] versus 9.1 [5 to 19], P < 0.0001 (median [quartile range]). In multivariate analysis, a low alarm rate was associated with activation of AutoFlow and a higher midazolam dose. CONCLUSIONS: This first long-term clinical evaluation of the AutoFlow mode demonstrated its safety with regard to gas exchange and patient outcome. AutoFlow also allowed a very marked reduction in the number of ventilator alarms.

A carbon monoxide-releasing molecule (CORM-3) exerts bactericidal activity against Pseudomonas aeruginosa and improves survival in an animal model of bacteraemia.

The search for new molecules to fight Pseudomonas aeruginosa is of paramount importance. Carbon monoxide (CO) is known to act as an effective inhibitor of the respiratory chain in P. aeruginosa, but the practical use of this gas as an antibacterial molecule is hampered by its toxicity and difficulty to manipulate. Here, we show that a water-soluble CO releaser (CORM-3) possesses bactericidal properties against laboratory and antibiotic-resistant P. aeruginosa. CORM-3 reduced the bacterial count by 4 logs 180 min after in vitro treatment. CORM-3-treated bacteria had a lower O(2) consumption than vehicle-treated bacteria, and the decrease in O(2) consumption temporally preceded the bactericidal action of CORM-3. These results support the hypothesis that the antimicrobial effect of CORM-3 is mediated by an interaction of CO liberated by the carrier with the bacterial respiratory chain. The antibacterial effect occurred at concentrations of CORM-3 that are 50-fold lower than toxic concentrations for eukaryotic cells. CORM-3 treatment compared to vehicle treatment decreased bacterial counts in the spleen and increased survival in immunocompetent and immunosuppressed mice following P. aeruginosa bacteremia. Our results suggest that CORMs could form the basis for developing a new therapeutic strategy against P. aeruginosa-induced infection.