Biomedical subjects
Publications and source records attributed to Christian Brun-Buisson.
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In addition to the IRB (Institutional review board), the DSMB (data safety and monitoring board) takes an increasing role in the monitoring of clinical trials, especially in large multicenter trials. The DSMB is a an expert committee, independent from the investigators and the sponsor of the trial, which periodically examines the safety data accumulated during progress of the trial and ensures that the benefit/risk ratio remains acceptable for participating patients. The DSMB is also a safeguard for the scientific integrity of the trial. It is the only committee which can have access to unblinded data from the trial. The DSMB may recommend termination of the trial in three situations : (1) occurrence of unanticipated adverse events which may pose a serious risk for participating patients; (2) demonstration of efficacy before the planned accrual \; (3) and because of "futility" (the most difficult situation), i.e. in absence of a reasonable probability that the trial may reach a conclusion within its planned frame.
The DSMB (data safety and monitoring board) takes an increasing role in the monitoring of clinical trials, especially in large multicenter trials conducted in populations at high risk of morbidity or mortality. The DSMB is a an expert committee, independent from the investigators and the sponsor of the trial, which periodically examines the safety data accumulated during progress of the trial and ensures that the benefit/risk ratio remains acceptable for participating patients. A few examples, derived for recent experience of clinical trials conducted in acutely ill patients, illustrate the importance of an efficient and reactive DSMB to monitor patients' safety, especially during large multicenter trials.
OBJECTIVE: To define central venous catheter-related infections in infants and children for the purpose of enrolling children in sepsis studies, for epidemiology and surveillance studies, and for clinical management. METHODS: Review of the literature and consensus of experts. RESULTS: No changes were made to the current Centers for Disease Control and Prevention criteria for defining local catheter infection. Because catheter tips are not available as often in children as in adults, smaller blood volumes are drawn per culture decreasing sensitivity, and antibiotics are rarely withheld, slight modifications to the existing adult Centers for Disease Control and Prevention criteria were made to increase practical use. Catheter-related bloodstream infection was categorized as definite, probable, and possible based on culture results and clinical symptoms. CONCLUSIONS: For the purposes of enrolling patients with sepsis in clinical trials, only patients who meet criteria for definite catheter-related bloodstream infection should be categorized as having the catheter as the infection source. Because many patients suspected of having catheter-related bloodstream infection do not have positive blood culture results, which makes the confirmation of infection difficult, we recommend that these patients not be enrolled in sepsis trials. Because catheter tips are often not obtained for culture in children, the epidemiology of catheter-associated bloodstream infection (bloodstream infection in a patient who has a central venous catheter and no other obvious source of infection) is better understood than the epidemiology of confirmed catheter-related bloodstream infection in infants and children. Definitions for catheter-related bloodstream infection that compare the through-catheter and peripheral culture for time to positivity or for quantitative growth are unlikely to be falsely positive, but sensitivity requires further validation.
OBJECTIVE: Sampling techniques for microbiological diagnosis of ventilator-associated pneumonia (VAP) remain debated, and it is unclear to what extent invasive diagnostic techniques impact the management of patients. DESIGN: A prospective observational study of 68 first episodes of suspected pneumonia in which specimens were obtained blindly (endotracheal aspirate [EA] and blinded protected telescoping catheter [PTC]) and via bronchoscopy (directed PTC bronchoscopy and BAL), and in sequence, and the results were provided to the attending physicians in the same order. Therapeutic plans resulting at each step were examined, and their adequacy was assessed using quantitative BAL fluid culture as the diagnostic standard. PARTICIPANTS: Sixty-eight patients with clinically suspected VAP hospitalized in two ICUs in a tertiary care university hospital. RESULTS: There were 35 patients (51%) with VAP confirmed by BAL fluid culture (13 early onset and 22 late onset). EA specimens grew organisms (light growth or more) in all BAL-confirmed VAP cases and 59% of nonconfirmed cases, whereas the sensitivity and specificity of blinded PTC quantitative cultures were 77% and 97%, and did not differ from those of directed PTC cultures (77% and 94%, respectively). Antibiotic therapy based on the clinical severity and likelihood of VAP, Gram stain results, and early blinded PTC culture results was adequate in 54% (19 of 35 VAP patients) within 2 h of sampling and 80% (28 of 35 patients) within 24 h; therapy was revised in only 3 more patients following BAL culture results. New antibiotics were introduced within the first 24 h in 14 of 33 nonconfirmed episodes (42%), and antibiotics were withheld or withdrawn within 48 h in 23 episodes (70%); three of these patients-with both blinded PTC and BAL growing organisms below the threshold-had early subsequently confirmed pneumonia with the same organism. CONCLUSIONS: A therapeutic approach guided by quantitative cultures of blinded specimens helps achieve early adequate management of approximately 90% of patients suspected of having VAP.
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An elderly patient dies from septic shock in the intensive care unit. This is perhaps not an unusual scenario, but in this case the sepsis happens to have been due to methicillin-resistant Staphylococcus aureus, possibly related to a catheter, and possibly transmitted from a patient in a neighbouring room by less than adequate compliance with infection control procedures. The family decides to sue. We present how experts from four different countries assess the medicolegal issues involved in this case.
RATIONALE: The systemic inflammatory response syndrome has low specificity to identify infected patients at risk of worsening to severe sepsis or shock. OBJECTIVE: To examine the incidence of and risk factors for worsening sepsis in infected patients. METHODS: A 1-year inception cohort study in 28 intensive care units of patients (n = 1,531) having a first episode of infection on admission or during the stay. MEASUREMENTS AND MAIN RESULTS: The cumulative incidence of progression to severe sepsis or shock was 20% and 24% at Days 10 and 30, respectively. Variables independently associated (hazard ratio [HR]) with worsening sepsis included: temperature higher than 38.2 degrees C (1.6), heart rate greater than 120/minute (1.3), systolic blood pressure higher than 110 mm Hg (1.5), platelets higher than 150 x 109/L (1.5), serum sodium higher than 145 mmol/L (1.5), bilirubin higher than 30 mumol/L (1.3), mechanical ventilation (1.5), and five variables characterizing infection (pneumonia [HR 1.5], peritonitis [1.5], primary bacteremia [1.8], and infection with gram-positive cocci [1.3] or aerobic gram-negative bacilli [1.4]). The 12 weighted variables were included in a score (Risk of Infection to Severe Sepsis and Shock Score, range 0-49), summarized in four classes of "low" (score 0-8) and "moderate" (8.5-16) risk (9% and 17% probability of worsening, respectively), and of "high" (16.5-24) and "very high" (score > 24) risk (31% and 55% probability, respectively). CONCLUSIONS: One of four patients presenting with infection/sepsis worsen to severe sepsis or shock. A score estimating this risk, using objectively defined criteria for systemic inflammatory response syndrome, could be used by physicians to stratify patients for clinical management and to test new interventions.
BACKGROUND: Ventilator-associated pneumonia (VAP) is an important patient safety issue in critically ill patients. PURPOSE: To develop an evidence-based guideline for the prevention of VAP. DATA SOURCES: MEDLINE, EMBASE, and the Cochrane Database of Systematic Reviews. STUDY SELECTION: The authors systematically searched for relevant randomized, controlled trials and systematic reviews that involved mechanically ventilated adults and were published before 1 April 2003. DATA EXTRACTION: Physical, positional, and pharmacologic interventions that may influence the development of VAP were considered. Independently and in duplicate, the authors scored the validity of trials; the effect size and confidence intervals; the homogeneity of results; and safety, feasibility, and economic issues. DATA SYNTHESIS: Recommended: The orotracheal route of intubation, changes of ventilator circuits only for each new patient and if the circuits are soiled, use of closed endotracheal suction systems that are changed for each new patient and as clinically indicated, heat and moisture exchangers in the absence of contraindications, weekly changes of heat and moisture exchangers, and semi-recumbent positioning in the absence of contraindications. Consider subglottic secretion drainage and kinetic beds. Not recommended: Sucralfate to prevent VAP in patients at high risk for gastrointestinal bleeding and topical antibiotics to prevent VAP. Because of insufficient or conflicting evidence, no recommendations were made about systematically searching for maxillary sinusitis, chest physiotherapy, the timing of tracheostomy, prone positioning, prophylactic intravenous antibiotics, or intravenous plus topical antibiotics. LIMITATIONS: No formal economic analysis was performed, and patient perspectives were not considered. CONCLUSION: If effectively implemented, this guideline may decrease the morbidity, mortality, and costs of VAP in mechanically ventilated patients.
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Explore the source record for details and available documents.
Explore the source record for details and available documents.
BACKGROUND: The indication of antiseptic-coated catheters remains debated. OBJECTIVE: To test the ability of the new generation of chlorhexidine-silver and sulfadiazine-coated catheters, with enhanced antiseptic coating, to reduce the risk of central venous catheter (CVC)-related infection in ICU patients. DESIGN: Multicentre randomized double-blind trial. PATIENTS AND SETTING: A total of 397 patients from 14 ICUs of university hospitals in France. INTERVENTION: Patients were randomized to receive an antiseptic-coated catheter (ACC) or a standard non-coated catheter (NCC). MEASUREMENTS: Incidence of CVC-related infection. RESULTS: Of 367 patients having a successful catheter insertion, 363 were analysed (175 NCC and 188 ACC). Patients had one (NCC=162, ACC=180) or more (NCC=13, ACC=11) CVC inserted. The two groups were similar for insertion site [subclavian (64 vs 69)] or jugular (36 vs 31%)], and type of catheters (single-lumen 18 vs 18%; double-lumen 82 vs 82%), and mean (median) duration of catheterisation [12.0+/-11.7 (9) vs 10.5+/-8.8 (8) days in the NCC and ACC groups, respectively]. Significant colonisation of the catheter occurred in 23 (13.1%) and 7 (3.7%) patients, respectively, in the NCC and ACC groups (11 vs 3.6 per 1000 catheter-days; p=0.01); CVC-related infection (bloodstream infection) occurred in 10 (5) and 4 (3) patients in the NCC and CC groups, respectively (5.2 vs 2 per 1000 catheter days; p=0.10). CONCLUSIONS: In the context of a low baseline infection rate, ACC were associated with a significant reduction of catheter colonisation and a trend to reduction of infection episodes, but not of bloodstream infection.
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OBJECTIVE: In 2003, critical care and infectious disease experts representing 11 international organizations developed management guidelines for the diagnosis of infection in sepsis that would be of practical use for the bedside clinician, under the auspices of the Surviving Sepsis Campaign, an international effort to increase awareness and improve outcome in severe sepsis. DESIGN: The process included a modified Delphi method, a consensus conference, several subsequent smaller meetings of subgroups and key individuals, teleconferences, and electronic-based discussion among subgroups and among the entire committee. METHODS: The modified Delphi methodology used for grading recommendations built on a 2001 publication sponsored by the International Sepsis Forum. We undertook a systematic review of the literature graded along five levels to create recommendation grades from A to E, with A being the highest grade. Pediatric considerations to contrast adult and pediatric management are in the article by Parker et al. on p. S591. CONCLUSIONS: Obtaining a precise bacteriological diagnosis before starting antibiotic therapy is, when possible, of paramount importance for the success of therapeutic strategy during sepsis. Two to three blood cultures should be performed, preferably from a peripheral vein, without interval between samples to avoid delaying therapy. A quantitative approach is preferred in most cases when possible, in particular for catheter-related infections and ventilator-associated pneumonia. Diagnosing community-acquired pneumonia is complex, and a diagnostic algorithm is proposed. Appropriate samples are indicated during soft tissue and intraabdominal infections, but cultures obtained through the drains are discouraged.
Poststernotomy mediastinitis (PSM) is one of the most serious complications of cardiac surgery, and its associated morbidity and mortality demand early recognition for emergency therapy. In this study, we investigated the usefulness of epicardial pacing wire (EPW) cultures for the prediction of PSM. Among 2,200 patients who underwent a cardiac surgical procedure at our hospital between 1 January 1999 and 31 December 2001, 82 (3.7%) had PSM; Staphylococcus aureus was the organism (45.1%) most frequently isolated at the time of surgical debridement. EPWs from 1,607 (73.0%) patients, 73 (4.5%) of whom developed PSM, were cultured. EPW cultures from 466 (29.0%) were positive, most often (74.9%) for coagulase-negative Staphylococci. EPW cultures were truly positive in 26 cases, truly negative in 1,106 cases, falsely positive in 428 cases, and falsely negative in 47 cases (with sterile cultures in 35 cases and a culture positive for an organism different from that isolated at the time of debridement in 12 cases). EPW culture had a positive predictive value of only 5.7% and a high negative predictive value (95.9%) for the diagnosis of PSM, with an accuracy of 70.4%. However, the likelihood ratio of positive (1.27) and negative (0.89) tests indicated only small changes in pretest-to-posttest probability. Therefore, a strategy of routine culture of EPWs to predict PSM seems questionable.
CONTEXT: Randomized controlled trials have shown that the use of noninvasive ventilation (NIV) reduces the need for endotracheal intubation and invasive mechanical ventilation and reduces complication rates and mortality in selected groups of patients. But whether these benefits translate to a clinical setting is unclear. OBJECTIVE: To evaluate longitudinally the routine implementation of NIV and its effect on patients admitted to the intensive care unit (ICU) with acute exacerbation of chronic obstructive pulmonary disease (COPD) or severe cardiogenic pulmonary edema (CPE). DESIGN: Retrospective, observational cohort study using prospectively collected data from January 1, 1994, through December 31, 2001. SETTING: A 26-bed medical intensive care unit (ICU) of a French university referral hospital. PARTICIPANTS: A cohort of 479 consecutive patients ventilated for acute exacerbation of COPD or CPE. MAIN OUTCOME MEASURES: The ICU mortality and incidence rates of ICU-acquired infections. RESULTS: A significant increase in NIV use and a concomitant decrease in mortality and ICU-acquired infection rates were observed over the study years. With adjustment for relevant covariates and propensity scores, NIV was identified as an independent factor linked with a reduced risk of death in the cohort (odds ratio [OR], 0.37; 95% confidence interval [CI], 0.18-0.78), whereas a high severity score on admission (OR, 1.05; 95% CI, 1.01-1.10) and the occurrence of a nosocomial infection (OR, 3.08; 95% CI, 1.62-5.84) were independently associated with death. Rates of ICU-acquired pneumonia decreased from 20% in 1994 to 8% in 2001 (P =.04). CONCLUSION: Implementing routine use of NIV in critically ill patients with acute exacerbation of COPD or severe CPE was associated with improved survival and reduction of nosocomial infections.
OBJECTIVES: To re-examine the epidemiology of acute lung injury (ALI) in European intensive care units (ICUs). DESIGN AND SETTING: A 2-month inception cohort study in 78 ICUs of 10 European countries. PATIENTS: All patients admitted for more than 4 h were screened for ALI and followed up to 2 months. MEASUREMENTS AND MAIN RESULTS: Acute lung injury occurred in 463 (7.1%) of 6,522 admissions and 16.1% of all mechanically ventilated patients; 65.4% cases occurred on ICU admission. Among 136 patients initially presenting with "mild ALI" (200< PaO2/FiO2 < or =300), 74 (55%) evolved to acute respiratory distress syndrome (ARDS) within 3 days. Sixty-two patients (13.4%) remained with mild ALI and 401 had ARDS. The crude ICU and hospital mortalities were 22.6% and 32.7% (p<0.001), and 49.4% and 57.9% (p=0.0005), respectively, for mild ALI and ARDS. ARDS patients initially received a mean tidal volume of 8.3+/-1.9 ml/kg and a mean PEEP of 7.7+/-3.6 cmH2O; air leaks occurred in 15.9%. After multivariate analysis, mortality was associated with age (odds ratio (OR) =1.2 per 10 years; 95% confidence interval (CI): 1.05-1.36), immuno-incompetence (OR: 2.88; Cl: 1.57-5.28), the severity scores SAPS II (OR: 1.16 per 10% expected mortality; Cl: 1.02-1.31) and logistic organ dysfunction (OR: 1.25 per point; Cl: 1.13-1.37), a pH less than 7.30 (OR: 1.88; Cl: 1.11-3.18) and early air leak (OR: 3.16; Cl: 1.59-6.28). CONCLUSIONS: Acute lung injury was frequent in our sample of European ICUs (7.1%); one third of patients presented with mild ALI, but more than half rapidly evolved to ARDS. While the mortality of ARDS remains high, that of mild ALI is twice as low, confirming the grading of severity between the two forms of the syndrome.