Jean-Yves Fagon

Nosocomial pneumonia in ventilated patients: A cohort study evaluating attributable mortality and hospital stay

PURPOSE Although nosocomial pneumonia is a common problem in intubated and ventilated patients, previous studies have not clearly demonstrated that nosocomial pneumonia actually results in increased mortality or prolongs hospitalization of these patients. In an attempt to answer these questions, we have performed a cohort study in which patients who developed nosocomial pneumonia and control subjects were carefully matched for the severity of underlying illness and other important variables. PATIENTS AND METHODS Case patients were 48 ventilated patients with nosocomial pneumonia identified on the basis of results of protected specimen brush quantitative culture and identification of intracellular organisms in cells recovered by bronchoalveolar lavage. For matching cases and their respective controls, the following variables were used: age (+/- 5 years), Simplified Acute Physiologic Score (+/- 3 points), indication for ventilatory support, date of admission, and duration of exposure to risk. RESULTS Successful matching was achieved for 222 of 240 (92.5%) variables. The mortality rate in cases was 26 of 48 (54.2%) compared with 13 of 48 (27.1%) in controls. The attributable mortality was 27.1% (95% confidence interval [CI], 8.3% to 45.9%; p < 0.01) and the risk ratio for death was 2.0 (95% CI, 1.61 to 2.49). The mean length of stay was 34 days for cases and 21 days for controls (p < 0.02). In the case of pneumonia due to Pseudomonas or Acinetobacter species, the mortality rate was 71.4%, the attributable mortality was 42.8% (95% CI, 14.5% to 69.0%), and the risk ratio was 2.50 (95% CI, 1.31 to 4.61). CONCLUSION Pneumonias occurring in ventilated patients, especially those due to Pseudomonas or Acinetobacter species, are associated with considerable mortality in excess of that resulting from the underlying disease alone, and significantly prolong the length of stay in the intensive care unit.

Invasive and Noninvasive Strategies for Management of Suspected Ventilator-Associated Pneumonia: A Randomized Trial

The diagnosis and treatment of ventilator-associated pneumonia, a nosocomial infection that develops in mechanically ventilated patients and causes considerable morbidity and mortality, remain a challenge (1-3). A presumptive clinical diagnosis of pneumonia is often made when a patient develops a new radiographic infiltrate associated with fever, leukocytosis, and purulent tracheal secretions and when microorganisms are isolated by nonquantitative analysis of endotracheal aspirates (4). This clinical approach leads to overestimation of the incidence of ventilator-associated pneumonia because cases of tracheobronchial colonization and noninfectious processes mimicking it are included (5-7). The nonspecificity of a strategy based on clinical evaluation has potentially deleterious consequences: Many patients may receive unneeded antibiotics; this exposes them to unnecessary toxicity, increases hospital costs, and favors the emergence of resistant microorganisms. In addition, antibiotic overuse in such patients delays diagnosis of the true cause of fever and pulmonary infiltrate. Concern about the inaccuracy of clinical approaches to diagnosis of ventilator-associated pneumonia led numerous investigators to postulate that invasive diagnostic methods, including quantitative cultures of specimens obtained by using bronchoscopic bronchoalveolar lavage or protected specimen brush, could improve identification of patients with true ventilator-associated pneumonia and selection of appropriate antibiotics (8-10). However, these procedures require rigorous adherence to bronchoscopic and microbiological techniques and are not universally available; moreover, in the absence of a definite gold standard for the diagnosis of ventilator-associated pneumonia, the value of such tests is uncertain, and their use in everyday practice remains controversial (4, 11, 12). To test the hypothesis that an invasive management strategy is superior to a clinical, noninvasive one in terms of improving clinical outcomes and minimizing antibiotic use, we initiated a multicenter, randomized, uncontrolled trial to compare these strategies in patients suspected of having ventilator-associated pneumonia. The primary end points were death from any cause, antibiotic use for any reason, and quantification of organ failure during the first 14 days of follow-up. Methods Patient Selection and Study Design After obtaining approval of the institutional review boards at each participating institution and informed consent from patients or their proxies, we enrolled patients at 31 intensive care units. Inclusion criteria were age older than 18 years; at least 48 hours of mechanical ventilation; and clinical suspicion of ventilator-associated pneumonia, defined by new and persistent infiltrate on chest radiography associated with at least one of the following: purulent tracheal secretions, body temperature of at least 38.3 C, and leukocytosis. Exclusion criteria were pregnancy; enrollment in another interventional study; little chance of survival, defined by a Simplified Acute Physiologic Score II (SAPS II) of more than 65 points (corresponding to a probability of death exceeding 77%) (13); and introduction or modification of antibiotic therapy, instigated by new clinical symptoms, during the 3 days before collection of respiratory samples. For patients in the clinical management group, the decision on whether to treat was based on clinical evaluation and results of immediate microscopic examination of Gram-stained endotracheal aspirates. The results of the Gram stain and recommendations of the American Thoracic Society on hospital-acquired pneumonia were used to guide the initial choice of antibiotics (3). Results of qualitative aspirate cultures were used to adjust the initial antibiotic regimen; when cultures were negative, no treatment was given (Figure 1 A). Figure 1. Diagnostic and therapeutic strategy applied to patients managed with the clinical strategy (A) or invasive strategy (B). The invasive strategy used fiberoptic bronchoscopy to obtain protected specimen brush samples or bronchoalveolar lavage samples for direct microscopic examination. Results of these examinations were used to diagnose ventilator-associated pneumonia, to decide to treat, and to guide the initial choice of antibiotics when specimens were positive. Results of quantitative cultures were used to adjust therapy; treatment was discontinued when results were negative, and use of antibiotics with narrower spectra of activity was based on identification of and susceptibility-test results for pathogens cultured at significant concentrations (protected specimen brush sample that yielded 103 colony-forming units [CFU]/mL or bronchoalveolar lavage fluid sample that yielded 104 CFU/mL [4, 8-10]) (Figure 1 B). For both groups, the recommended duration of therapy for ventilator-associated pneumonia was 14 days. Randomization and Data Collection Patients were randomly assigned to receive the clinical or the invasive management strategy. Computer-generated random-number tables were used to assign patients in blocks of 8, with stratification according to treatment center. At admission to the intensive care unit, we recorded each patients age; sex; severity of underlying medical condition, stratified as rapidly fatal, ultimately fatal, or not fatal according to the criteria of McCabe and Jackson (14); SAPS II score (range, 0 to 174; higher scores indicate more severe illness) (13); Sepsis-related Organ Failure Assessment (SOFA) score (range, 0 to 24, with scores for each organ system [respiration, coagulation, liver, cardiovascular, central nervous system, and kidney] ranging from 0 [normal] to 4 [most abnormal]) (15); the Organ Dysfunction and Infection (ODIN) score (range, 0 to 7, according to the presence or absence of cardiovascular, respiratory, renal, hepatic, hematologic, and neurologic dysfunctions or infection) (16); classification as medical patient, surgical patient with trauma, or surgical patient without trauma according to the admitting diagnosis; and reason for initiating mechanical ventilation (17). The following baseline variables were recorded before randomization: SAPS II score; SOFA score; ODIN score; body temperature; leukocyte count; radiologic score (range, 0 to 12 according to the density of radiologic infiltration) (18); ratio of the partial pressure of arterial oxygen to the fraction of inspired oxygen (Pao 2/Fio 2); presence of shock, defined as systolic arterial pressure less than 90 mm Hg with signs of peripheral hypoperfusion or need for continuous infusion of vasopressor or inotropic agents (19); and presence of the acute respiratory distress syndrome, defined as the presence of a generalized pulmonary infiltrate and a lung injury score more than 2.5 (20); duration of previous mechanical ventilation; and use or no use of antibiotics. These baseline variables (except SAPS II score) were measured again 3, 7, 14, 21, and 28 days after the day of inclusion. All infections requiring specific therapeutic measures during the first 3 days after inclusion were recorded. Antibiotic use was recorded daily until day 28. Specimen Collection and Microbiological Processing Patients who received invasive management underwent fiberoptic bronchoscopy according to each centers protocol. Premedication, use of a short-acting neuromuscular blocking agent, and adjustment of Fio 2 to 95% or more were recommended; protected specimen brush, bronchoalveolar lavage, or both were performed at the investigators discretion. Processing of microbiological specimens has been described in detail elsewhere (10, 21). Briefly, recovered bronchoalveolar lavage fluid was divided into two samples: one for direct microscopic examination of cytocentrifuge preparations after Gram or modified Wright-Giemsa staining to determine the percentages of cells containing intracellular bacteria, and the other for quantitative cultures. The tip of the protected specimen brush was cut, dropped into 1 mL of sterile water, and vortexed for 1 minute; samples were examined directly and serially diluted for culture. The number of bacteria in the original specimens was estimated by colony counts and is expressed as CFU/mL. Patients in the invasive treatment group were considered to have ventilator-associated pneumonia if more than 5% of the cells in cytocentrifuge preparations of bronchoalveolar lavage fluid contained intracellular bacteria or at least one bacterial species grew at a significant concentration from the protected specimen brush sample ( 103 CFU/mL) or from bronchoalveolar lavage fluid ( 104 CFU/mL) (10, 22). In patients who received clinical treatment, endotracheal aspirates were collected sterilely by using a suction catheter in a mucus collector; secretions were aspirated without instilling saline. Aspirates were vortexed for 1 minute; Gram staining and qualitative aerobic cultures were performed for all patients. Definitions Inappropriate treatment, evaluated initially and at 3 days, was defined as the use of antibiotics to which at least one cultured isolate was resistant in vitro. For patients in the clinical management group, all pathogens grown in qualitative endotracheal aspirate cultures were considered for this analysis; for patients in the invasive management group, only pathogens cultured at significant concentrations were taken into account. Resistant bacteria were defined as ticarcillin-resistant Pseudomonas aeruginosa, Acinetobacter baumannii, and Stenotrophomonas maltophilia; extended-spectrum -lactamase-producing Enterobacteriaceae; and methicillin-resistant Staphylococcus aureus. We calculated the number of antibiotic-free days (days without antibiotic therapy) at 14 and 28 days after inclusion. For example, a patient who survived 28 days and received no antibiotics was assigned a value of 28. If antibiotics had been given for 10 days and the patient died on day 14, a value of 4 was assign

Characterization of intensive care unit patients using a model based on the presence or absence of organ dysfunctions and/or infection: The ODIN model

ObjectiveTo evaluate the sensitivity, specificity and overall accuracy of a model based on the presence or absence of organ dysfunctions and/or infection (ODIN) to predict the outcome for intensive care unit patients.DesignProspective study.SettingGeneral intensive care unit in a university teaching hospital.Patients1070 consecutive, unselected patients.InterventionsThere were no interventions.Measurements and main resultsWe recorded within the first 24h of admission the presence or absence of dysfunction in 6 organ systems: respiratory, cardiovascular, renal, hematologic, hepatic and neurologic, and/or infection (ODIN) in all patients admitted to our ICU, thus establishing a profile of organ dysfunctions in each patient. Using univariate analysis, a strong correlation was found between the number of ODIN and the death rate (2.6, 9.7, 16.7, 32.3, 64.9, 75.9, 94.4 and 100% for 0, 1, 2, 3, 4, 5, 6 and 7 ODIN, respectively; (p<0.001). In addition, the highest mortality rates were associated with hepatic (60.8%), hematologic (58.1%) and renal (54.8%) dysfunctions, and the lowest with respiratory dysfunction (36.5%) and infection (38.3%). For taking into account both the number and the type of organ dysfunction, a logistic regression model was then used to calculate individual probabilities of death that depended upon the statistical weight assigned to each ODIN (in the following order of descending severity: cardiovascular, renal, respiratory, neurologic, hematologic, hepatic dysfunctions and infection). The ability of this severity-of-disease classification system to stratify a wide variety of patients prognostically (sensitivity 51.4%, specificity 93.4%, overall accuracy 82.1%) was not different from that of currently used scoring systems.ConclusionsThese findings suggest that determination of the number and the type of organ dysfunctions and infection offers a clear and reliable method for characterizing ICU patients. Before a widespread use, this model requires to be validated in other institutions.

Critically ill old and the oldest-old patients in intensive care: short- and long-term outcomes

ObjectiveThe purpose of this study was to examine characteristics and outcome of the old, very old and oldest-old ICU patientsDesignThis is a cohort study.SettingThe study was set in a ten-bed medical ICU in a university hospital.ParticipantsThere were 410 patients classified in three subgroups: old, 75–79 years (n=184; 44.4%), very old, 80–84 (n=137, 33.4%) and the oldest-old, ≥85 (n=91; 22.2%).MeasurementsUnderlying medical conditions, organ dysfunction, severity of illness, length of stay, use of mechanical ventilation, therapeutic activity and nosocomial infections were recorded. Multivariate analysis was conducted to identify risk factors for ICU and long-term mortality.ResultsCharacteristics at ICU admission did not differ among the three groups. ICU length of stay, therapeutic activity, mechanical ventilation and nosocomial infection(s) decreased with age. ICU survival rates for those below 75, 75–79, 80–84 and over 85 years were 80, 68, 75 and 69%, respectively; survival rates at 3 months were 54, 56 and 51%, respectively. APACHE II score [odds ratio (OR): 1.11] was identified as the only factor associated with ICU mortality, and age (OR: 2.17, for patients ≥85 years old and 1.82, for patients 80–84 years old) and limitation of activity before admission (OR: 1.74) as factors associated with long-term mortality.ConclusionIn a population of patients ≥75 years old, very old age is not directly associated with ICU mortality. After ICU discharge, deaths occurred predominantly during the first 3 months: age and prior limitation of activity were associated with the risk of dying.

Telavancin versus Vancomycin for Hospital-Acquired Pneumonia due to Gram-positive Pathogens

The results from two methodologically identical double-blind studies indicate that telavancin is noninferior to vancomycin based on clinical response in the treatment of hospital-acquired pneumonia due to Gram-positive pathogens.

Prevalence, etiologies and outcome of the acute respiratory distress syndrome among hypoxemic ventilated patients

Objective: To evaluate the prevalence and outcome of the acute respiratory distress syndrome (ARDS) among patients requiring mechanical ventilation. Design: A prospective, multi-institutional, initial cohort study including 28-day follow-up. Settings: Thirty-six French intensive care units (ICUs) from a working group of the French Intensive Care Society (SRLF). Patients: All the patients entering the ICUs during a 14-day period were screened prospectively. Hypoxemic patients, defined as having a PaO2/FIO2 ratio (P/F) of 300 mmHg or less and receiving mechanical ventilation, were classified into three groups, according to the Consensus Conference on ARDS: group 1 refers to ARDS (P/F: 200 mmHg or less and bilateral infiltrates on the chest X-ray); group 2 to acute lung injury (ALI) without having criteria for ARDS (200 < P/F ≤ 300 mmHg and bilateral infiltrates) and group 3 to patients with P/F of 300 mmHg or less but having exclusion criteria from the previous groups. Results: Nine hundred seventy-six patients entered the ICUs during the study period, 43 % of them being mechanically ventilated and 213 (22 %) meeting the criteria for one of the three groups. Among all the ICU admissions, ARDS, ALI and group 3 patients amounted, respectively, to 6.9 % (67), 1.8 % (17) and 13.3 % (129) of the patients, and represented 31.5 %, 8.1 % and 60.2 % of the hypoxemic, ventilated patients. The overall mortality rate was 41 % and was significantly higher in ARDS patients than in the others (60 % vs 31 % p < 0.01). In group 3, 42 patients had P/F less than 200 mmHg associated with unilateral lung injury; mortality was significantly lower (40.5 %) than in the ARDS group. In the whole group of hypoxemic, ventilated patients, septic shock and severity indices but not oxygenation indices were significantly associated with mortality, while the association with immunosuppression revealed only a trend (p = 0.06). Conclusions: In this survey we found that very few patients fulfilled the ALI non-ARDS criteria and that the mortality of the group with ARDS was high.

Value of the clinical pulmonary infection score for the identification and management of ventilator-associated pneumonia

ObjectiveTo evaluate the potential ability of an algorithm based on the clinical pulmonary infection score (CPIS) to identify and treat patients with bacterial ventilator-associated pneumonia (VAP) compared to a strategy based on quantitative cultures of bronchoscopic specimens.DesignRetrospective cohort study.SettingThirty-one critical care units across France.PatientsTwo hundred and one patients clinically suspected of having VAP who had been included in the “invasive strategy” group of the French multicenter randomized trial and for whose quantitative cultures bronchoscopic specimens were obtained. CPIS was determined retrospectively, based on data that had been collected for the initial study.InterventionsNone.Measurements and resultsThe clinical pulmonary infection score was determined on days 1 and 3, and compared in patients identified as having developed VAP or not, as defined by bronchoscopic specimen culture results. On day 3 138 of the 201 patients (69%) had a CPIS of more than 6 that would have required prolonged antimicrobial therapy based on the algorithm. In contrast, based on bronchoscopy, only 88 (44%) patients were considered to have VAP (kappa coefficient for concordance between the two strategies, 0.33). While the sensitivity of CPIS more than 6 on day 3 for identifying VAP was 89%, its specificity was only 47%, leading to potentially unnecessary treatment of 60 (53%) of the 113 patients without VAP as diagnosed by bronchoscopy.ConclusionA strategy based on the CPIS to decide which patients with suspected VAP should receive prolonged administration of antibiotics would appear to over-prescribe these agents, as compared to a strategy based on bronchoscopy.

Improvement of internal jugular vein cannulation using an ultrasound-guided technique

Objective: To determine whether ultrasound guidance can help operators to improve the results of jugular vein access in the ICU. Design: Prospective, randomized study. Setting: General Intensive Care Unit of a University Hospital. Patients: Seven-nine patients were assigned to internal jugular vein cannulation using anatomical landmarks alone (control group, n = 42) or with ultrasound guidance (ultrasound group, n = 37). Intervention: All cannulations were performed by junior house staff under the direct supervision of a senior physician. In the ultrasound group, an ultrasonography (7.5 MHz) was used and the transducer was covered by a sterile sheath. The placement and direction of the cannulating needle were determined on the ultrasound image. Measurements and results: Internal jugular vein cannulation was successful in 37/37 (100 %) patients in the ultrasound group and in 32/42 patients (76 %) in the control group (p < 0.01). Average access time was longer in the control group (235 ± 408 s vs 95 ± 174 s, p = 0.06) and carotid artery puncture occurred in five patients in each group (p = 0.83). Jugular cannulation was successful at the first attempt in 26 % in the control group and 43 % in the ultrasound group (p = 0.11). Thirty-two patients (86 %) in the ultrasound group and 23 patients (55 %) in the control group (p < 0.05) were cannulated within 3 min. The cannula could therefore not be inserted within 3 min in 19 patients (45 %) in the control group. Failure was explained by thrombosis (n = 1), small caliber of the internal jugular vein (< 5 mm, n = 3), abnormal vascular relations (n = 3). Among the ten primary failures of cannulation, an internal jugular vein catheter was able to be inserted in four cases by an experienced physician on the side initially selected and with ultrasound guidance in two cases. The catheter was inserted into the contralateral internal jugular vein under ultrasound guidance in the remaining four cases. Conclusion: Ultrasound guidance improved the success rate of jugular vein cannulation in ICU patients. Our results suggest that ultrasound guidance should be used when the internal jugular vein has not been successfully cannulated within 3 min by the external landmark-guided technique.

Impact of energy deficit calculated by a predictive method on outcome in medical patients requiring prolonged acute mechanical ventilation

To assess energy balance in very sick medical patients requiring prolonged acute mechanical ventilation and its possible impact on outcome, we conducted an observational study of the first 14 d of intensive care unit (ICU) stay in thirty-eight consecutive adult patients intubated at least 7 d. Exclusive enteral nutrition (EN) was started within 24 h of ICU admission and progressively increased, in absence of gastrointestinal intolerance, to the recommended energy of 125.5 kJ/kg per d. Calculated energy balance was defined as energy delivered - resting energy expenditure estimated by a predictive method based on static and dynamic biometric parameters. Mean energy balance was - 5439 (sem 222) kJ per d. EN was interrupted 23 % of the time and situations limiting feeding administration reached 64 % of survey time. ICU mortality was 72 %. Non-survivors had higher mean energy deficit than ICU survivors (P = 0.004). Multivariate analysis identified mean energy deficit as independently associated with ICU death (P = 0.02). Higher ICU mortality was observed with higher energy deficit (P = 0.003 comparing quartiles). Using receiver operating characteristic curve analysis, the best deficit threshold for predicting ICU mortality was 5021 kJ per d. Kaplan-Meier analysis showed that patients with mean energy deficit > or =5021 kJ per d had a higher ICU mortality rate than patients with lower mean energy deficit after the 14th ICU day (P = 0.01). The study suggests that large negative energy balance seems to be an independent determinant of ICU mortality in a very sick medical population requiring prolonged acute mechanical ventilation, especially when energy deficit exceeds 5021 kJ per d.

Bronchoalveolar lavage for rapid diagnosis of the fat embolism syndrome in trauma patients.

OBJECTIVE To evaluate the usefulness of bronchoalveolar lavage in establishing the diagnosis of the fat embolism syndrome in trauma patients with long-bone fractures. DESIGN Case series. SETTING Referral hospital. PATIENTS Eighteen trauma patients with long-bone fractures, including 5 with definite fat embolism syndrome, 5 in whom the diagnosis had been clinically suspected but was impossible to confirm or exclude before bronchoscopy, and 8 with no clinical evidence of the syndrome. Control groups included 9 patients without previous trauma who developed the adult respiratory distress syndrome for various reasons and 15 normal volunteers. MEASUREMENTS AND MAIN RESULTS Each patient had fiber-optic bronchoscopy with bronchoalveolar lavage, and the percentage of lavage cells containing intracellular fat droplets stained with oil red 0 were determined. In the five patients with definite fat embolism syndrome, light microscopic study of bronchoalveolar cells stained with oil red 0 showed many large intracellular fat droplets (mean percentage of cells containing fat droplets, 63%; range, 31% to 82%), whereas less than 2% of cells recovered by lavage from trauma patients with no clinical evidence of the syndrome, from patients with the adult respiratory distress syndrome, or from normal volunteers contained such inclusions. Use of the same technique in the five patients with possible fat embolism syndrome permitted the immediate identification of three patients in whom this diagnosis was later confirmed by subsequent autopsy or clinical follow-up. CONCLUSIONS The identification of fat droplets within cells recovered by bronchoalveolar lavage in trauma patients may be a rapid and specific method for establishing the diagnosis of the fat embolism syndrome.