Emmanuelle Mercier

Prone Positioning in Severe Acute Respiratory Distress Syndrome

BACKGROUND Previous trials involving patients with the acute respiratory distress syndrome (ARDS) have failed to show a beneficial effect of prone positioning during mechanical ventilatory support on outcomes. We evaluated the effect of early application of prone positioning on outcomes in patients with severe ARDS. METHODS In this multicenter, prospective, randomized, controlled trial, we randomly assigned 466 patients with severe ARDS to undergo prone-positioning sessions of at least 16 hours or to be left in the supine position. Severe ARDS was defined as a ratio of the partial pressure of arterial oxygen to the fraction of inspired oxygen (FiO2) of less than 150 mm Hg, with an FiO2 of at least 0.6, a positive end-expiratory pressure of at least 5 cm of water, and a tidal volume close to 6 ml per kilogram of predicted body weight. The primary outcome was the proportion of patients who died from any cause within 28 days after inclusion. RESULTS A total of 237 patients were assigned to the prone group, and 229 patients were assigned to the supine group. The 28-day mortality was 16.0% in the prone group and 32.8% in the supine group (P<0.001). The hazard ratio for death with prone positioning was 0.39 (95% confidence interval [CI], 0.25 to 0.63). Unadjusted 90-day mortality was 23.6% in the prone group versus 41.0% in the supine group (P<0.001), with a hazard ratio of 0.44 (95% CI, 0.29 to 0.67). The incidence of complications did not differ significantly between the groups, except for the incidence of cardiac arrests, which was higher in the supine group. CONCLUSIONS In patients with severe ARDS, early application of prolonged prone-positioning sessions significantly decreased 28-day and 90-day mortality. (Funded by the Programme Hospitalier de Recherche Clinique National 2006 and 2010 of the French Ministry of Health; PROSEVA ClinicalTrials.gov number, NCT00527813.).

EffectofNotMonitoringResidualGastricVolume on Risk of Ventilator-Associated Pneumonia in Adults Receiving Mechanical Ventilation and Early Enteral Feeding A Randomized Controlled Trial

IMPORTANCE Monitoring of residual gastric volume is recommended to prevent ventilator-associated pneumonia (VAP) in patients receiving early enteral nutrition. However, studies have challenged the reliability and effectiveness of this measure. OBJECTIVE To test the hypothesis that the risk of VAP is not increased when residual gastric volume is not monitored compared with routine residual gastric volume monitoring in patients receiving invasive mechanical ventilation and early enteral nutrition. DESIGN, SETTING, AND PATIENTS Randomized, noninferiority, open-label, multicenter trial conducted from May 2010 through March 2011 in adults requiring invasive mechanical ventilation for more than 2 days and given enteral nutrition within 36 hours after intubation at 9 French intensive care units (ICUs); 452 patients were randomized and 449 included in the intention-to-treat analysis (3 withdrew initial consent). INTERVENTION Absence of residual gastric volume monitoring. Intolerance to enteral nutrition was based only on regurgitation and vomiting in the intervention group and based on residual gastric volume greater than 250 mL at any of the 6 hourly measurements and regurgitation or vomiting in the control group. MAIN OUTCOME MEASURES Proportion of patients with at least 1 VAP episode within 90 days after randomization, as assessed by an adjudication committee blinded to patient group. The prestated noninferiority margin was 10%. RESULTS In the intention-to-treat population, VAP occurred in 38 of 227 patients (16.7%) in the intervention group and in 35 of 222 patients (15.8%) in the control group (difference, 0.9%; 90% CI, -4.8% to 6.7%). There were no significant between-group differences in other ICU-acquired infections, mechanical ventilation duration, ICU stay length, or mortality rates. The proportion of patients receiving 100% of their calorie goal was higher in the intervention group (odds ratio, 1.77; 90% CI, 1.25-2.51; P = .008). Similar results were obtained in the per-protocol population. CONCLUSION AND RELEVANCE Among adults requiring mechanical ventilation and receiving early enteral nutrition, the absence of gastric volume monitoring was not inferior to routine residual gastric volume monitoring in terms of development of VAP. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT01137487.

Respiratory pulse pressure variation fails to predict fluid responsiveness in acute respiratory distress syndrome

IntroductionFluid responsiveness prediction is of utmost interest during acute respiratory distress syndrome (ARDS), but the performance of respiratory pulse pressure variation (ΔRESPPP) has scarcely been reported. In patients with ARDS, the pathophysiology of ΔRESPPP may differ from that of healthy lungs because of low tidal volume (Vt), high respiratory rate, decreased lung and sometimes chest wall compliance, which increase alveolar and/or pleural pressure. We aimed to assess ΔRESPPP in a large ARDS population.MethodsOur study population of nonarrhythmic ARDS patients without inspiratory effort were considered responders if their cardiac output increased by >10% after 500-ml volume expansion.ResultsAmong the 65 included patients (26 responders), the area under the receiver-operating curve (AUC) for ΔRESPPP was 0.75 (95% confidence interval (CI95): 0.62 to 0.85), and a best cutoff of 5% yielded positive and negative likelihood ratios of 4.8 (CI95: 3.6 to 6.2) and 0.32 (CI95: 0.1 to 0.8), respectively. Adjusting ΔRESPPP for Vt, airway driving pressure or respiratory variations in pulmonary artery occlusion pressure (ΔPAOP), a surrogate for pleural pressure variations, in 33 Swan-Ganz catheter carriers did not markedly improve its predictive performance. In patients with ΔPAOP above its median value (4 mmHg), AUC for ΔRESPPP was 1 (CI95: 0.73 to 1) as compared with 0.79 (CI95: 0.52 to 0.94) otherwise (P = 0.07). A 300-ml volume expansion induced a ≥2 mmHg increase of central venous pressure, suggesting a change in cardiac preload, in 40 patients, but none of the 28 of 40 nonresponders responded to an additional 200-ml volume expansion.ConclusionsDuring protective mechanical ventilation for early ARDS, partly because of insufficient changes in pleural pressure, ΔRESPPP performance was poor. Careful fluid challenges may be a safe alternative.

Prognosis and 1-year mortality of intensive care unit patients with severe hepatic encephalopathy ☆

PURPOSE Data regarding outcome of patients with chronic liver disease with severe hepatic encephalopathy in intensive care unit are currently scarce. METHODS This study is a retrospective observational case series in a medical intensive care unit (ICU) in a university hospital from 1995 to 2005. Patients with hepatic encephalopathy (HE) (admitted with or developing) were identified. Clinical and laboratory parameters were analyzed to determinate predictors of ICU and 1-year mortality. RESULTS Seventy-one patients were included (53 male). Median Simplified Acute Physiology Score was 56 with Child-Pugh score 11 +/- 2. Seventy-six percent of patients were admitted with coma (Glasgow Coma Scale, 7.7 +/- 4). Eighty-two percent of patients required intubation, and 28% vasopressors. Thirty-five percent died during ICU stay. At 1 year, mortality was 54%. Univariate analysis identified arterial hypotension, mechanical ventilation, vasopressors at any time, acute renal failure, Simplified Acute Physiology Score, and sepsis associated with ICU mortality. In multivariate analysis, vasopressor use or acute renal failure was the main independent predictor of ICU death and 1-year mortality. Patients free of these risk factors, even requiring intubation, were identified as isolated HE, with lower mortality rates. CONCLUSION Predictors of outcome were similar to other groups of patients with liver disease admitted for other reasons. Intensive care unit mortality was lower than reported for other groups of patients with similar illness. Patients with severe HE admitted to ICU with no organ dysfunction other than mechanical ventilation had a better outcome and may require ICU admission.

Video Laryngoscopy vs Direct Laryngoscopy on Successful First-Pass Orotracheal Intubation Among ICU Patients: A Randomized Clinical Trial.

Importance In the intensive care unit (ICU), orotracheal intubation can be associated with increased risk of complications because the patient may be acutely unstable, requiring prompt intervention, often by a practitioner with nonexpert skills. Video laryngoscopy may decrease this risk by improving glottis visualization. Objective To determine whether video laryngoscopy increases the frequency of successful first-pass orotracheal intubation compared with direct laryngoscopy in ICU patients. Design, Setting, and Participants Randomized clinical trial of 371 adults requiring intubation while being treated at 7 ICUs in France between May 2015 and January 2016; there was 28 days of follow-up. Interventions Intubation using a video laryngoscope (n = 186) or direct laryngoscopy (n = 185). All patients received general anesthesia. Main Outcomes and Measures The primary outcome was the proportion of patients with successful first-pass intubation. The secondary outcomes included time to successful intubation and mild to moderate and severe life-threatening complications. Results Among 371 randomized patients (mean [SD] age, 62.8 [15.8] years; 136 [36.7%] women), 371 completed the trial. The proportion of patients with successful first-pass intubation did not differ significantly between the video laryngoscopy and direct laryngoscopy groups (67.7% vs 70.3%; absolute difference, −2.5% [95% CI, −11.9% to 6.9%]; P = .60). The proportion of first-attempt intubations performed by nonexperts (primarily residents, n = 290) did not differ between the groups (84.4% with video laryngoscopy vs 83.2% with direct laryngoscopy; absolute difference 1.2% [95% CI, −6.3% to 8.6%]; P = .76). The median time to successful intubation was 3 minutes (range, 2 to 4 minutes) for both video laryngoscopy and direct laryngoscopy (absolute difference, 0 [95% CI, 0 to 0]; P = .95). Video laryngoscopy was not associated with life-threatening complications (24/180 [13.3%] vs 17/179 [9.5%] for direct laryngoscopy; absolute difference, 3.8% [95% CI, −2.7% to 10.4%]; P = .25). In post hoc analysis, video laryngoscopy was associated with severe life-threatening complications (17/179 [9.5%] vs 5/179 [2.8%] for direct laryngoscopy; absolute difference, 6.7% [95% CI, 1.8% to 11.6%]; P = .01) but not with mild to moderate life-threatening complications (10/181 [5.4%] vs 14/181 [7.7%]; absolute difference, −2.3% [95% CI, −7.4% to 2.8%]; P = .37). Conclusions and Relevance Among patients in the ICU requiring intubation, video laryngoscopy compared with direct laryngoscopy did not improve first-pass orotracheal intubation rates and was associated with higher rates of severe life-threatening complications. Further studies are needed to assess the comparative effectiveness of these 2 strategies in different clinical settings and among operators with diverse skill levels. Trial Registration clinicaltrials.gov Identifier: NCT02413723

Tracking Hypotension and Dynamic Changes in Arterial Blood Pressure with Brachial Cuff Measurements

BACKGROUND: Arterial cannulation is strongly recommended during shock. Nevertheless, this procedure is associated with significant risks and may delay other emergent procedures. We assessed the discriminative power of brachial cuff oscillometric noninvasive blood pressure (NIBP) for identifying patients with an invasive mean arterial blood pressure (MAP) below 65 mm Hg or increasing their invasive MAP after cardiovascular interventions. METHODS: This prospective study, conducted in three intensive care units, included adults in circulatory failure who underwent 45° passive leg raising, 300 mL fluid loading, and additional 200 mL fluid loading. The collected data were four invasive and noninvasive MAP measurements at each study phase. RESULTS: Among 111 patients (50 septic, 15 cardiogenic, and 46 other source of shock), when averaging measurements of each study phase, NIBP measurements accurately predicted an invasive MAP lower than 65 mm Hg: area under the receiver operating characteristic curve 0.90 (95% CI: 0.71–1), positive and negative likelihood ratios 7.7 (95% CI: 5.4–11) and 0.31 (95% CI: 0.22–0.44) (cutoff 65 mm Hg). For identifying patients increasing their invasive MAP by more than 10%, the area under the receiver operating characteristic curve was 0.95 (95% CI: 0.92–0.96); positive and negative likelihood ratios (cutoff 10%) were 25.7 (95% CI: 10.8–61.4) and 0.26 (95% CI: 0.2–0.34). CONCLUSIONS: NIBP measurements have a good discriminative power for identifying hypotensive patients and performed even better in tracking MAP changes, provided that one averages four NIBP measurements.

Population pharmacokinetics of ceftriaxone in critically ill septic patients: a reappraisal

AIMS To investigate the population pharmacokinetics of ceftriaxone in critically ill patients suffering from sepsis, severe sepsis or septic shock. METHODS Blood samples were collected at preselected times in 54 adult patients suffering from sepsis, severe sepsis or septic shock in order to determine ceftriaxone concentrations using high-performance liquid chromatography-ultraviolet detection. The pharmacokinetics of ceftriaxone were assessed on two separate occasions for each patient: on the second day of ceftriaxone therapy and 48 h after catecholamine withdrawal in patients with septic shock, or on the fifth day in patients with sepsis. The population pharmacokinetics of ceftriaxone were studied using nonlinear mixed effects modelling. RESULTS The population estimates (interindividual variability; coefficient of variation) for ceftriaxone pharmacokinetics were: a clearance of 0.88 l h(-1) (49%), a mean half-life of 9.6 h (range 0.83-28.6 h) and a total volume of distribution of 19.5 l (range 6.48-35.2 l). The total volume of distribution was higher than that generally found in healthy individuals and increased with the severity of sepsis. However, the only covariate influencing the ceftriaxone pharmacokinetics was creatinine clearance. Dosage simulations showed that the risk of ceftriaxone concentrations dropping below the minimum inhibitory concentration threshold was low. CONCLUSIONS Despite the wide interpatient variability of ceftriaxone pharmacokinetic parameters, our results revealed that increasing the ceftriaxone dosage when treating critically ill patients is unnecessary. The risk of ceftriaxone concentrations dropping below the minimum inhibitory concentration threshold is limited to patients with high glomerular filtration rates or infections with high minimum inhibitory concentration pathogens (>1 mg l(-1)).

Association of Necrotizing Wounds Colonized by Maggots with Ignatzschineria-Associated Septicemia.

To the Editor: Ignatzschineria is a recently described genus of bacteria that have been rarely implicated in human disease (1–3). We report a patient in France with septicemia caused by I. ureiclastica.

Early Detection of Disseminated Intravascular Coagulation During Septic Shock: A Multicenter Prospective Study.

Objectives:Inadequate stratification of septic shock patients may result in inappropriate treatment allocation in randomized clinical trials, especially regarding anticoagulant. We previously reported that endothelial-derived microparticles are relevant biomarkers of sepsis-induced disseminated intravascular coagulation. In this validation cohort, we assess microparticles as surrogates of cell activation to improve early disseminated intravascular coagulation diagnosis and patient stratification. Design:Prospective observational study in septic shock patients. Settings:Four medical ICUs in university hospitals. Patients and Methods:Two hundred sixty-five patients with septic shock from four ICUs were consecutively enrolled. Disseminated intravascular coagulation was diagnosed according to Japanese Association for Acute Medicine 2006 score. Endothelial- and leukocyte-derived circulating procoagulant microparticles were isolated and quantified by prothrombinase assay at admission, day 3, and day 7. Intervention:None. Measurements and Main Results:Two hundred fifty-nine patients were analyzed. Sixty-one had disseminated intravascular coagulation at admission, and 32 developed disseminated intravascular coagulation during the first 24 hours after admission. Multiple logistic regression model confirmed that endothelial cell-derived microparticles were associated with disseminated intravascular coagulation: CD105+-microparticles (odds ratio, 2.13) and CD31+-microparticles (odds ratio, 0.65) (p < 0.05). Furthermore, CD11a+-microparticles to leukocyte ratio evidenced leukocyte activation (odds ratio, 1.59; p < 0.05). Prediction of disseminated intravascular coagulation was also analyzed after exclusion of patients with disseminated intravascular coagulation at admission. A new multiple logistic regression analysis demonstrated the association of CD105+-microparticles (> 0.60 nM eq. PhtdSer; odds ratio, 1.67; p < 0.01), platelets count (⩽ 127 g/L; odds ratio, 0.99; p < 0.01), and prothrombin time (⩽ 58%; odds ratio, 0.98; p < 0.05) with disseminated intravascular coagulation. A combining score at admission is predictive of the absence of disseminated intravascular coagulation (area under the curve, 72.9%; specificity, 71.2%; sensitivity, 71.0%, with a negative predictive value of 93.1% and a positive predictive value of 31.0%). Conclusions:Procoagulant microparticles from endothelial cells and leukocytes reflect a vascular injury during sepsis-induced disseminated intravascular coagulation that precedes obvious activation of coagulation. A combination of prothrombin time, endothelium-derived CD105+-microparticles, and platelet count at admission could predict the absence of disseminated intravascular coagulation and allow a better stratification in future randomized clinical trials.

Atteinte respiratoire sévère et choc septique à Mycobacterium bovis: Une complication rare de la BCG thérapie intravésicale

INTRODUCTION Intravesical bacillus Calmette-Guerin (BCG) therapy, recommended for superficial bladder tumors, triggers side effects in fewer than 5% of patients. The most severe side effects, however, are septic shock and acute respiratory failure. CASE A 70-year-old man was hospitalized for septic shock with acute respiratory and renal failure after intravesical instillation of BCG, which was identified in the gastric aspiration sample. Treatment with rifampicin, ethambutol, isoniazid, and corticosteroid therapy, as well as standard reanimation measures, led to the patients recovery. DISCUSSION This case shows the potentially severe side effects of intravesical BCG instillation. Although this treatment is well tolerated in more than 95% of patients and its systemic complications can be effectively treated, these side effects can be life-threatening.