Respiratory changes of the inferior vena cava diameter predict fluid responsiveness in spontaneously breathing patients with cardiac arrhythmias.

BACKGROUND: Whether the respiratory changes of the inferior vena cava diameter during a deep standardized inspiration can reliably predict fluid responsiveness in spontaneously breathing patients with cardiac arrhythmia is unknown. METHODS: This prospective two-center study included nonventilated arrhythmic patients with infection-induced acute circulatory failure. Hemodynamic status was assessed at baseline and after a volume expansion of 500 mL 4% gelatin. The inferior vena cava diameters were measured with transthoracic echocardiography using the bi-dimensional mode on a subcostal long-axis view. Standardized respiratory cycles consisted of a deep inspiration with concomitant control of buccal pressures and passive exhalation. The collapsibility index of the inferior vena cava was calculated as [(expiratory-inspiratory)/expiratory] diameters. RESULTS: Among the 55 patients included in the study, 29 (53%) were responders to volume expansion. The areas under the ROC curve for the collapsibility index and inspiratory diameter of the inferior vena cava were both of 0.93 [95% CI 0.86; 1]. A collapsibility index ≥ 39% predicted fluid responsiveness with a sensitivity of 93% and a specificity of 88%. An inspiratory diameter < 11 mm predicted fluid responsiveness with a sensitivity of 83% and a specificity of 88%. A correlation between the inspiratory effort and the inferior vena cava collapsibility was found in responders but was absent in nonresponder patients. CONCLUSIONS: In spontaneously breathing patients with cardiac arrhythmias, the collapsibility index and inspiratory diameter of the inferior vena cava assessed during a deep inspiration may be noninvasive bedside tools to predict fluid responsiveness in acute circulatory failure related to infection. These results, obtained in a small and selected population, need to be confirmed in a larger-scale study before considering any clinical application.

Diagnostic Accuracy of the Inferior Vena Cava Collapsibility to Predict Fluid Responsiveness in Spontaneously Breathing Patients With Sepsis and Acute Circulatory Failure.

OBJECTIVE: To investigate whether the collapsibility index of the inferior vena cava recorded during a deep standardized inspiration predicts fluid responsiveness in nonintubated patients. DESIGN: Prospective, nonrandomized study. SETTING: ICUs at a general and a university hospital. PATIENTS: Nonintubated patients without mechanical ventilation (n = 90) presenting with sepsis-induced acute circulatory failure and considered for volume expansion. INTERVENTIONS: We assessed hemodynamic status at baseline and after a volume expansion induced by a 30-minute infusion of 500-mL gelatin 4%. MEASUREMENTS AND MAIN RESULTS: We measured stroke volume index and collapsibility index of the inferior vena cava under a deep standardized inspiration using transthoracic echocardiography. Vena cava pertinent diameters were measured 15-20 mm caudal to the hepatic vein junction and recorded by bidimensional imaging on a subcostal long-axis view. Standardized respiratory cycles consisted of a deep standardized inspiration followed by passive exhalation. The collapsibility index expressed in percentage equaled the ratio of the difference between end-expiratory and minimum-inspiratory diameter over the end-expiratory diameter. After volume expansion, a relevant (≥ 10%) stroke volume index increase was recorded in 56% patients. In receiver operating characteristic analysis, the area under curve for that collapsibility index was 0.89 (95% CI, 0.82-0.97). When such index is superior or equal to 48%, fluid responsiveness is predicted with a sensitivity of 84% and a specificity of 90%. CONCLUSIONS: The collapsibility index of the inferior vena cava during a deep standardized inspiration is a simple, noninvasive bedside predictor of fluid responsiveness in nonintubated patients with sepsis-related acute circulatory failure.

The use of static and dynamic haemodynamic parameters before volume expansion: A prospective observational study in six French intensive care units.

OBJECTIVE: The aim of the present study was to determine the use of static and dynamic haemodynamic parameters for predicting fluid responsiveness prior to volume expansion (VE) in intensive care unit (ICU) patients with systemic inflammatory response syndrome (SIRS). METHODS: We conducted a prospective, multicentre, observational study in 6 French ICUs in 2012. ICU physicians were audited concerning their use of static and dynamic haemodynamic parameters before each VE performed in patients with SIRS for 6 consecutive weeks. RESULTS: The median volume of the 566 VEs administered to patients with SIRS was 1000mL [500-1000mL]. Although at least one static or dynamic haemodynamic parameter was measurable before 99% (95% CI, 99%-100%) of VEs, at least one them was used in only 38% (95% CI, 34%-42%) of cases: static parameters in 11% of cases (95% CI, 10%-12%) and dynamic parameters in 32% (95% CI, 30%-34%). Static parameters were never used when uninterpretable. For 15% of VEs (95% CI, 12%-18%), a dynamic parameter was measured in the presence of contraindications. Among dynamic parameters, respiratory variations in arterial pulse pressure (PPV) and passive leg raising (PLR) were measurable and interpretable before 17% and 90% of VEs, respectively. CONCLUSIONS: Haemodynamic parameters are underused for predicting fluid responsiveness in current practice. In contrast to static parameters, dynamic parameters are often incorrectly used in the presence of contraindications. PLR is more frequently valid than PPV for predicting fluid responsiveness in ICU patients.

Endotoxemia Engages the RhoA Kinase Pathway to Impair Cardiac Function By Altering Cytoskeleton, Mitochondrial Fission, and Autophagy.

AIMS: The RhoA/ROCK pathway controls crucial biological processes involved in cardiovascular pathophysiology, such as cytoskeleton dynamics, vascular smooth muscle contraction, and inflammation. In this work, we tested whether Rho kinase inhibition would beneficially impact cardiac cytoskeleton organization, bioenergetics, and autophagy in experimental endotoxemia induced by lipopolysaccharides (LPSs) in mice. RESULTS: Fasudil, a potent ROCK inhibitor, prevented LPS-induced cardiac inflammation, oxidative stress, cytoskeleton disarray, and mitochondrial injury. ROCK inhibition prevented phosphorylation of cofilin and dynamin-related protein-1, which promotes stabilization-polymerization of F-actin and mediates mitochondrial fission, respectively. Pyr1, which exclusively alters actin dynamics, prevented LPS-induced myocardial dysfunction, suggesting that beneficial impact of ROCK inhibition was not mainly related to pleiotropic effects of fasudil on cardiac inflammation and oxidative stress. Fasudil reduced mitochondrial fragmentation, stimulated initiation of autophagy, and elicited cardioprotection in LPS heart. Mdivi-1, a potent mitochondria fission inhibitor, converted cardioprotective autophagy to an inefficient form due to cargo loading failure in which autophagic vacuoles fail to trap cytosolic cargo, despite their formation at enhanced rates and lysosomal elimination. INNOVATION: In experimental endotoxemia, cardioprotection by RhoA/ROCK inhibition may be related to changes in actin cytoskeleton reorganization and mitochondrial homeostasis. Improvement of LPS-induced mitochondrial dysfunction by fasudil was attributed to inhibition of ROCK-dependent Drp1 phosphorylation and activation of autophagic processes that can limit mitochondrial fragmentation and enhance degradation of damaged mitochondria, respectively. CONCLUSION: Fasudil prevented LPS-induced heart oxidative stress, abnormal F-actin distribution, and oxidative phosphorylation, which concur to improve cardiac contractile and bioenergetic function. We suggest that fasudil may represent a valuable therapy for patients with sepsis.

Infective endocarditis requiring ICU admission: epidemiology and prognosis.

BACKGROUND: Very few studies focused on patients with severe infective endocarditis (IE) and multiple complications leading to Intensive Care Unit (ICU) admission. Studied primary outcomes depended on the series and multiple prognostic factors have been identified. Our goal was to determinate characteristics of patients, in-hospital mortality and independent prognostic factors in an overall population of patients admitted to ICU for a left-sided, definite, active and severe IE. METHODS: Retrospective study performed in 9 ICUs during an 11-year period. RESULTS: Data of 248 patients (mean age = 62.4 ± 13.3 years; 63.7 % male) were studied. Native and prosthetic valves were involved in 195 and 53 patients, respectively. Causative pathogens, identified in 225 patients, were mainly streptococci (45.6 %) and staphylococci (43.4 %). On ICU admission, 127 patients exhibited extra-cardiac involvement. Ninety-five patients had one or more neurological complications, as followed: ischemic stroke (n = 66), cerebral hemorrhage (n = 31), meningitis (n = 16), brain abscess (n = 16), and intracranial mycotic aneurysm (n = 10). Criteria prompting to cardiac surgery appeared during ICU stay for 186 patients and between ICU and hospital discharges in 5 patients. Due to contra-indications, surgery required by IE was only performed during hospitalization in 125 patients. Moreover, surgery was considered adequate according to usual guidelines in 76 of 191 patients with indication(s) of valvular surgery: for patients with surgical procedure considered as emergency (n = 69), 17 surgical procedures underwent within the first 24 h following indication; for patients with urgent surgical indication (n = 102), surgery was performed during the first week following indication in 40 patients; finally, elective surgery (n = 20) was performed for 19 patients. During hospitalization, 103 (41.5 %) patients died. Four independent prognostic factors were identified: SAPS II > 35 (AOR = 2.604; 95 % CI: 1.320-5.136; p = 0.0058), SOFA > 8 (AOR = 3.327; 95 % CI: 1.697-6.521; p = 0.0005), IE due to methicillin resistant Staphylococcus aureus (AOR = 4.981; 95 %CI = 1.433-17.306; p = 0.0115) and native IE (AOR = 0.345; 95 % CI: 0.169-0.703; p = 0.0034). CONCLUSIONS: Mortality in patients admitted to ICU for left-sided IE remains high, especially in cases of endocarditis due to methicillin resistant Staphylococcus aureus, when organ failures occur and ICU scores are high.

New tools for optimizing fluid resuscitation in acute pancreatitis.

Acute pancreatitis (AP) is a frequent disease with degrees of increasing severity responsible for high morbidity. Despite continuous improvement in care, mortality remains significant. Because hypovolemia, together with microcirculatory dysfunction lead to poor outcome, fluid therapy remains a cornerstone of the supportive treatment. However, poor clinical evidence actually support the aggressive fluid therapy recommended in recent guidelines since available data are controversial. Fluid management remains unclear and leads to current heterogeneous practice. Different strategies may help to improve fluid resuscitation in AP. On one hand, integration of fluid therapy in a global hemodynamic resuscitation has been demonstrated to improve outcome in surgical or septic patients. Tailored fluid administration after early identification of patients with high-risk of poor outcome presenting inadequate tissue oxygenation is a major part of this strategy. On the other hand, new decision parameters have been developed recently to improve safety and efficiency of fluid therapy in critically ill patients. In this review, we propose a personalized strategy integrating these new concepts in the early fluid management of AP. This new approach paves the way to a wide range of clinical studies in the field of AP.

Assessing alcohol versus baclofen withdrawal syndrome in patients treated with baclofen for alcohol use disorder.

Baclofen is a γ-aminobutyric acid B (GABA-B) receptor agonist that is approved for spasticity. Recently, the off-label use of baclofen for alcohol use disorder (AUD) has increased. However, baclofen is known to induce a neuroadaptation process, which may be identified by the occurrence of a specific baclofen withdrawal syndrome (BWS), that is, confusion, agitation, seizures, and delirium. The same set of symptoms characterizes alcohol withdrawal syndrome (AWS), which could lead to mistaking BWS for AWS in some situations. We report the cases of 3 patients under a chronic baclofen treatment for AUD. The patients emergently presented with a clinical state of confusion that was initially diagnosed and treated as AWS, with limited effect of benzodiazepines. Retrospectively, using a validated algorithm for assessing drug-induced withdrawal, we determined that all of these clinical cases were consistent with BWS. Both AWS and BWS should be considered in the case of acute confusion or delirium occurring in patients treated with baclofen for AUD. Moreover, further research should investigate to what extent GABA-A and GABA-B induce shared or distinct neuroadaptation processes and withdrawal syndromes.

Macrophage migration inhibitory factor induces contractile and mitochondria dysfunction by altering cytoskeleton network in the human heart.

OBJECTIVES: Macrophage migration inhibitory factor (MIF) has been recognized as a potent proinflammatory mediator that may induce myocardial dysfunction. Mechanisms by which MIF affects cardiac function are not completely elucidated; yet, some macrophage migration inhibitory effects have been related to changes in cytoskeleton architecture. We hypothesized that MIF-induced myocardial dysfunction and mitochondrial respiration deficit could be related to cardiac cell microtubule dynamics alterations. DESIGN: Prospective, randomized study. SETTING: Experimental Cardiovascular Laboratory, University Hospital. SUBJECTS: Human myocardial (atrial) trabeculae. INTERVENTIONS: Atrial trabeculae were obtained at the time of cardiac surgery. Isometrically contracting isolated human right atrial trabeculae were exposed to MIF (100 ng/mL) for 60 minutes, in the presence or not of pretreatment with colchicine (10 µM), a microtubule-depolymerizing agent, or paclitaxel (10 µM) a microtubule-stabilizing agent. MEASUREMENTS AND MAIN RESULTS: Maximal active isometric tension curve and developed isometric force were studied. Trabeculae were then permeabilized for mitochondrial respiration studies using high-resolution oxygraphy. Heart fiber electron microscopy and visualization of ßIV tubulin and polymerized actin by confocal microscopy were used to evaluate sarcomere and microtubule disarray. Compared with controls, MIF elicited cardiac contractile and mitochondrial dysfunction, which were largely prevented by pretreatment with colchicine, but not by paclitaxel. Pretreatment with colchicine prevented MIF-induced microtubule network disorganization, excessive tubulin polymerization, and mitochondrial fragmentation. Compound-C, an inhibitor of AMP-activated protein kinase (AMPK), partially prevented contractile dysfunction, suggesting that cardiac deleterious effects of MIF were related to AMPK activation. CONCLUSIONS: MIF depresses human myocardial contractile function and impairs mitochondrial respiration. Changes in microtubule network likely promote MIF-induced cardiac dysfunction by 1) altering with mitochondrial tubular assembly and outer membrane permeability for adenine nucleotides leading to energy deficit, 2) excessive tubulin polymerization that may impede cardiomyocyte viscosity and motion, and 3) interfering with AMPK pathway.

A comparison of survival with and without extracorporeal life support treatment for severe poisoning due to drug intoxication.

BACKGROUND: The use of extracorporeal life support (ECLS) as a treatment for severe cardiovascular impairment due to poisoning is unclear. Therefore, we conducted a retrospective cohort analysis to compare survival among critically ill poisoned patients treated with or without ECLS. METHODS: All consecutive patients admitted into 2 university hospitals in northwestern France over the past decade for persistent cardiac arrest or severe shock following poisoning due to drug intoxication were included. ECLS was preferentially performed in 1 of the 2 centers. RESULTS: Sixty-two patients (39 women, 23 men; mean age 48±17 years) fulfilled inclusion criteria: 10 with persistent cardiac arrest and 42 with severe shock. Fourteen patients were treated with ECLS and 48 patients with conventional therapies. All subjects received vasopressor and fluid loading. Patients treated with or without ECLS at ICU admission had comparable drug ingestion histories, Simplified Acute Physiology Score (SAPS II score) (66±18), Sequential Organ Failure Assessment (SOFA) score (median: 11 [IQR, 9-13]), Glasgow Coma Scale score (median: 3 [IQR, 3-11]), need for ventilator support (n=56) and extra renal support (n=23). Thirty-five (56%) patients survived: 12/14 (86%) ECLS patients and 23/48 (48%) non-ECLS patients (p=0.02, by Fisher exact test). None of the patients with persistent cardiac arrest survived without ECLS support. Based on admission data, beta-blocker intoxication (p=0.02) was also associated with lower mortality. In multivariate analysis, adjusting for SAPS II and beta-blocker intoxication, ECLS support remained associated with lower mortality [Adjusted Odds Ratio, 0.18; 95% CI, 0.03-0.96; p=0.04]. CONCLUSION: In the absence of response to conventional therapies, we consider that ECLS may improve survival in critically ill poisoned patients experiencing cardiac arrest and severe shock.

Hemodynamic changes during a deep inspiration maneuver predict fluid responsiveness in spontaneously breathing patients.

OBJECTIVE: We hypothesized that the hemodynamic response to a deep inspiration maneuver (DIM) indicates fluid responsiveness in spontaneously breathing (SB) patients. DESIGN: Prospective study. SETTING: ICU of a general hospital. PATIENTS: Consecutive nonintubated patients without mechanical ventilation, considered for volume expansion (VE). INTERVENTION: We assessed hemodynamic status at baseline and after VE. MEASUREMENTS AND MAIN RESULTS: We measured radial pulse pressure (PP) using an arterial catheter and peak velocity of femoral artery flow (VF) using continuous Doppler. Changes in PP and VF induced by a DIM (ΔPPdim and ΔVFdim) were calculated in 23 patients. ΔPPdim and ΔVFdim ≥12% predicted responders to VE with sensitivity of 90% and specificity of 100%. CONCLUSIONS: In a restricted population of SB patients with severe sepsis or acute pancreatitis, ΔPPdim and ΔVFdim are accurate indices for predicting fluid responsiveness. These results should be confirmed in a larger population before validating their use in current practice.

The conservative management of severe caustic gastric injuries.

OBJECTIVE: To determine the safety of a conservative approach to treating severe caustic injury in patients lacking clinical and biochemical signs of transmural necrosis. BACKGROUND: Esophagogastrectomy is thought to limit the progression of severe caustic injury in the upper gastrointestinal tract observed upon initial endoscopic examination. However, endoscopic evaluation of the depth and spread of necrosis is challenging and may lead to unnecessary gastrectomy. METHODS: From January 2002 to December 2008, 70 patients were classified as having stage III gastric injury in an initial digestive tract endoscopic examination. When patients had no signs of peritonitis, their treatment was determined by 6 clinical and biochemical factors of severity (abdominal rebound tenderness, neuropsychiatric troubles, cardiovascular shock, metabolic acidosis, disseminated intravascular coagulation, and kidney failure) in addition to endoscopic staging. If one of these clinical and biochemical factors was present, the patient underwent emergency laparotomy. Patients with isolated stage III gastric injury were kept under close observation. RESULTS: Twenty-four of the 70 endoscopic stage III patients required emergency surgery. Conservative treatment was initiated in the remaining 46. There were 4 postoperative deaths (5.7%). Fifteen patients required subsequent surgery: distal gastrectomy with Billroth I anastomosis (n = 7) for distal stricture and esophagoplasty for nondilatable esophageal stricture (n = 8). At the end of the follow-up period, total or partial gastric conservation was achieved in all 46 patients (65.7%) and the esophagus was conserved in 38 patients (54.3%). CONCLUSION: In the absence of clinical and biological signs of severity, conservative management of stage III gastric injury is clinically feasible, precludes gastrectomy and has a low mortality rate.

Passive leg raising is predictive of fluid responsiveness in spontaneously breathing patients with severe sepsis or acute pancreatitis.

OBJECTIVE: Rapid fluid loading is standard treatment for hypovolemia. Because volume expansion does not always improve hemodynamic status, predictive parameters of fluid responsiveness are needed. Passive leg raising is a reversible maneuver that mimics rapid volume expansion. Passive leg raising-induced changes in stroke volume and its surrogates are reliable predictive indices of volume expansion responsiveness for mechanically ventilated patients. We hypothesized that the hemodynamic response to passive leg raising indicates fluid responsiveness in nonintubated patients without mechanical ventilation. DESIGN: Prospective study. SETTING: Intensive care unit of a general hospital. PATIENTS: We investigated consecutive nonintubated patients, without mechanical ventilation, considered for volume expansion. INTERVENTIONS: We assessed hemodynamic status at baseline, after passive leg raising, and after volume expansion (500 mL 6% hydroxyethyl starch infusion over 30 mins). MEASUREMENTS AND MAIN RESULTS: We measured stroke volume using transthoracic echocardiography, radial pulse pressure using an arterial catheter, and peak velocity of femoral artery flow using continuous Doppler. We calculated changes in stroke volume, pulse pressure, and velocity of femoral artery flow induced by passive leg raising (respectively, Deltastroke volume, Deltapulse pressure, and Deltavelocity of femoral artery flow). Among 34 patients included in this study, 14 had a stroke volume increase of >or=15% after volume expansion (responders). All patients included in the study had severe sepsis (n = 28; 82%) or acute pancreatitis (n = 6; 18%). The Deltastroke volume >or=10% predicted fluid responsiveness with sensitivity of 86% and specificity of 90%. The Deltapulse pressure >or=9% predicted fluid responsiveness with sensitivity of 79% and specificity of 85%. The Deltavelocity of femoral artery flow >or=8% predicted fluid responsiveness with sensitivity of 86% and specificity of 80%. CONCLUSIONS: Changes in stroke volume, radial pulse pressure, and peak velocity of femoral artery flow induced by passive leg raising are accurate and interchangeable indices for predicting fluid responsiveness in nonintubated patients with severe sepsis or acute pancreatitis.

Methodological approach for the evaluation of the performances of medical intensive care units.

PURPOSE: The purpose of the study was to present a methodological approach enabling the comparison of clinical and economic performances of intensive care units and a graphical visualization based on these 2 dimensions. PATIENTS AND METHODS: A retrospective analysis of a database of 666 patients admitted in intensive care units over a period of 2 consecutive months. RESULTS: Calculation of clinical performance is based on the difference between the mortality observed and forecast from the Simplified Acute Physiology Score version 2. The evaluation of resource consumption is carried out from the measure of medical and paramedical care workload. These 2 scores are modeled on the basis of the length of stay and the severity state of the patient. The economic performance is calculated on the basis of the difference between the resource consumption observed and forecast. The graphs are constructed by taking up as coordinates the values of the clinical and economic performances of each center. CONCLUSION: These graphs enable the identification of the most deviating intensive care units to study, for example, their organizational, technical, or human resource setup accounting for their position.

Can dynamic indicators help the prediction of fluid responsiveness in spontaneously breathing critically ill patients?

OBJECTIVE: To investigate whether the respiratory changes in arterial pulse (DeltaPP) and in systolic pressure (DeltaSP) could predict fluid responsiveness in spontaneously breathing (SB) patients. Because changes in intrathoracic pressure during spontaneous breathing (SB) might be insufficient to modify loading conditions of the ventricles, performances of indicators were also assessed during a forced respiratory maneuver. DESIGN: Prospective interventional study. SETTING: A 34-bed university hospital medico-surgical ICU. PATIENTS AND PARTICIPANTS: Thirty-two SB patients with clinical signs of hemodynamic instability. INTERVENTION: A 500-ml volume expansion (VE). MEASUREMENTS AND RESULTS: Cardiac index, assessed using transthoracic echocardiography, increased by at least 15% after VE in 19 patients (responders). At baseline, only dynamic indicators were higher in responders than in nonresponders (13+/-5% vs. 7+/-3%, p=0.003 for DeltaPP and 10+/-4% vs. 6+/-2%, p=0.002 for DeltaSP). Moreover, they significantly decreased after VE (11+/-5% to 6+/-4%, p<0.001 for DeltaPP and 8+/-4% to 6+/-3%, p<0.001 for DeltaSP). DeltaPP and DeltaSP areas under the ROC curve were high (0.81+/-0.08 and 0.82+/-0.08; p=0.888, respectively). A DeltaPP>or=12% predicted fluid responsiveness with high specificity (92%) but poor sensitivity (63%). The forced respiratory maneuver reproducing a dyspneic state decreased the predictive power. CONCLUSIONS: Due to their lack of sensitivity and their dependence to respiratory status, DeltaPP and DeltaSP are clearly less reliable to predict fluid responsiveness during SB than in mechanically ventilated patients. However, when their baseline value is high without acute right ventricular dysfunction in a participating patient, a positive response to fluid is likely.

Multiple-drug-resistant bacteria in patients with severe acute exacerbation of chronic obstructive pulmonary disease: Prevalence, risk factors, and outcome.

OBJECTIVE: To determine prevalence, risk factors, and effect on outcome of multiple-drug-resistant (MDR) bacteria in patients with severe acute exacerbation of chronic obstructive pulmonary disease. DESIGN: Prospective, observational, cohort study. SETTING: Thirty-bed medical intensive care unit (ICU) in a university hospital. METHODS: All chronic obstructive pulmonary disease patients with acute exacerbation who required intubation and mechanical ventilation for >48 hrs were eligible during a 4-yr period. Patients with pneumonia or other causes of acute respiratory failure were not eligible. In all patients, quantitative tracheal aspirate was performed at ICU admission (positive at 10 colony-forming units [cfu]/mL). MDR bacteria were defined as methicillin-resistant Staphylococcus aureus, ceftazidime- or imipenem-resistant Pseudomonas aeruginosa, Acinetobacter baumannii, Stenotrophomonas maltophilia, and extended-spectrum beta-lactamase-producing Gram-negative bacilli. All patients received empirical antibiotic treatment at ICU admission. Univariate and multivariate analyses were used to determine variables associated with MDR bacteria and variables associated with ICU mortality. RESULTS: A total of 857 patients were included, and 304 bacteria were isolated (>/=10 cfu/mL) in 260 patients (30%), including 75 MDR bacteria (24%) in 69 patients (8%). When patients with MDR bacteria were compared with patients without MDR bacteria, previous antimicrobial treatment (odds ratio [OR], 2.4; 95% confidence interval [95% CI], 1.2-4.7; p = .013) and previous intubation (OR, 31; 95% CI, 12-82; p < .001) were independently associated with MDR bacteria. When patients with bacteria other than MDR or patients with no bacteria were used as a reference group, these risk factors were still independently associated with MDR bacteria. Although ICU mortality rate was higher in patients with MDR bacteria than in patients without MDR bacteria (44% vs. 25%; p = .001; OR, 2.3; 95% CI, 1.4-3.8), MDR bacteria were not independently associated with ICU mortality. Inappropriate initial antibiotic treatment (88% vs. 5%; p = <.001; OR, 6.7; 95% CI, 3.8-12) and ventilator-associated pneumonia (23% vs. 5%; p = <.001; OR, 1.3; 95% CI, 1-1.8) rates were significantly higher in patients with MDR bacteria than in patients with bacteria other than MDR. Inappropriate initial antibiotic treatment was independently associated with increased ICU mortality (OR, 7.1; 95% CI, 1.9-30; p = .003). CONCLUSION: MDR bacteria are common in patients with acute exacerbation of chronic obstructive pulmonary disease requiring intubation and mechanical ventilation. Previous antimicrobial treatment and previous intubation are independent risk factors for MDR bacteria. Although MDR bacteria are not independently associated with ICU mortality, inappropriate initial antibiotic treatment is an independent risk factor for ICU mortality in these patients. Further studies are needed to determine whether broad-spectrum antibiotic treatment is cost-effective in these patients.

Impact of ventilator-associated pneumonia on outcome in patients with COPD.

PURPOSES: The aim of this study was to determine the impact of ventilator-associated pneumonia (VAP) on outcome in patients with COPD. METHODS: Prospective, observational, case-control study conducted in a 30-bed ICU during a 5-year period. All COPD patients who required intubation and mechanical ventilation (MV) for > 48 h were eligible. VAP diagnosis was based on clinical, radiographic, and quantitative microbiologic criteria. Patients with unconfirmed VAP were excluded, as well as patients with ventilator-associated tracheobronchitis without subsequent VAP. Matching (1:1) criteria included MV duration before VAP occurrence, age +/- 5 years, simplified acute physiology score II on ICU admission +/- 5, and ICU admission category. Variables associated with ICU mortality were determined using univariate and multivariate analyses. RESULTS: A total of 1,241 patients were eligible; 181 patients (14%) were excluded, including 133 patients for VAT and 48 patients for unconfirmed VAP. VAP developed in 77 patients (6%), and all were successfully matched. Pseudomonas aeruginosa was the most frequently isolated bacteria (31%). ICU mortality rate (64% vs 28%), duration of MV (24 +/- 15 d vs 13 +/- 11 d [+/- SD]), and ICU stay (26 +/- 17 d vs 15 +/- 13 d) were significantly (< 0.001) higher in case patients than in control patients. VAP was the only variable independently associated with ICU mortality (odds ratio [OR], 7.7; 95% confidence interval [CI], 3.2 to 18.6; p < 0.001). In VAP patients who received corticosteroids during their ICU stay compared with those who did not receive corticosteroids, mortality rate (50% vs 82%; OR, 1.8; 95% CI, 1.2 to 2.7; p = 0.002), duration of MV (21 +/- 14 d vs 27 +/- 16 d, p = 0.043), and ICU stay (22 +/- 16 d vs 31 +/- 18 d, p = 0.006) were significantly lower. CONCLUSION: VAP is associated with increased mortality rates and longer duration of MV and ICU stay in COPD patients.

Effect of ventilator-associated tracheobronchitis on outcome in patients without chronic respiratory failure: a case-control study.

INTRODUCTION: Our objective was to determine the effect of ventilator-associated tracheobronchitis (VAT) on outcome in patients without chronic respiratory failure. METHODS: This was a retrospective observational matched study, conducted in a 30-bed intensive care unit (ICU). All immunocompetent, nontrauma, ventilated patients without chronic respiratory failure admitted over a 6.5-year period were included. Data were collected prospectively. Patients with nosocomial pneumonia, either before or after VAT, were excluded. Only first episodes of VAT occurring more than 48 hours after initiation of mechanical ventilation were studied. Six criteria were used to match cases with controls, including duration of mechanical ventilation before VAT. Cases were compared with controls using McNemar's test and Wilcoxon signed-rank test for qualitative and quantitative variables, respectively. Variables associated with a duration of mechanical ventilation longer than median were identified using univariate and multivariate analyses. RESULTS: Using the six criteria, it was possible to match 55 (87%) of the VAT patients (cases) with non-VAT patients (controls). Pseudomonas aeruginosa was the most frequently isolated bacteria (34%). Although mortality rates were similar between cases and controls (29% versus 36%; P = 0.29), the median duration of mechanical ventilation (17 days [range 3-95 days] versus 8 [3-61 days]; P < 0.001) and ICU stay (24 days [range 5-95 days] versus 12 [4-74] days; P < 0.001) were longer in cases than in controls. Renal failure (odds ratio [OR] = 4.9, 95% confidence interval [CI] = 1.6-14.6; P = 0.004), tracheostomy (OR = 4, 95% CI = 1.1-14.5; P = 0.032), and VAT (OR = 3.5, 95% CI = 1.5-8.3; P = 0.004) were independently associated with duration of mechanical ventilation longer than median. CONCLUSION: VAT is associated with longer durations of mechanical ventilation and ICU stay in patients not suffering from chronic respiratory failure.

First-generation fluoroquinolone use and subsequent emergence of multiple drug-resistant bacteria in the intensive care unit.

OBJECTIVE: The objective of this study was to determine the relationship between fluoroquinolone (FQ) use and subsequent emergence of multiple drug-resistant bacteria (MRB) in the intensive care unit (ICU). DESIGN: The authors conducted a prospective observational cohort study and a case control study. SETTING: The study was conducted in a 30-bed ICU. METHODS: All immunocompetent patients hospitalized for >48 hrs who did not receive antibiotics before ICU admission were eligible during a 15-month period. Routine MRB screening was performed at ICU admission and weekly thereafter. This screening included tracheal aspirate and nasal, anal, and axilla swabs. Univariate and multivariate analyses were used to determine risk factors for MRB emergence in the ICU. In addition, a case control study was performed to determine whether FQ use is associated with subsequent emergence of MRB. RESULTS: Two hundred thirty-nine patients were included; 108 ICU-acquired MRB were isolated in 77 patients. FQ use and longer duration of antibiotic treatment were identified as independent risk factors for MRB occurrence (odds ratio [95% confidence interval [CI] = 3.3 [1.7-6.5], 1.1 [1.0-1.2]; p < .001; respectively). One hundred thirty-five (56%) patients received FQ; matching was successful for 72 (53%) of them. Number of MRB (40 vs. 15 per 1,000 ICU days; p = .019) and percentage of patients with MRB (40% vs. 22%; OR [95% CI] = 1.5 [1.0-2.4]; p = .028) were significantly higher in cases than in controls. Although methicillin-resistant Staphylococcus aureus (26% vs. 12%; OR [95% CI] = 1.6 [.6-2.9]; p = .028) and extending-spectrum beta-lactamase-producing Gram-negative bacilli (11% vs. 1%; OR [95% CI] = 4.7 [0.7-30.2]; p = .017) rates were higher in cases than in controls, ceftazidime or imipenem-resistant Pseudomonas aeruginosa (15% vs. 8%), Acinetobacter baumannii (1% vs. 5%), and Stenotrophomonas maltophilia (2% vs. 1%) rates were similar (p > .05) in case and control patients. CONCLUSION: FQ use and longer duration of antibiotic treatment are independently associated with MRB emergence. Reducing antimicrobial treatment duration and restricting FQ use could be suggested to control MRB spread in the ICU.