One-Year Outcomes in Patients With Acute Stroke Requiring Mechanical Ventilation.

BACKGROUND: Long-term outcomes of patients with severe stroke remain poorly documented. We aimed to characterize one-year outcomes of patients with stroke requiring mechanical ventilation in the intensive care unit (ICU). METHODS: We conducted a prospective multicenter cohort study in 33 ICUs in France (2017-2019) on patients with consecutive strokes requiring mechanical ventilation for at least 24 hours. Outcomes were collected via telephone interviews by an independent research assistant. The primary end point was poor functional outcome, defined by a modified Rankin Scale score of 4 to 6 at 1 year. Multivariable mixed models investigated variables associated with the primary end point. Secondary end points included quality of life, activities of daily living, and anxiety and depression in 1-year survivors. RESULTS: Among the 364 patients included, 244 patients (66.5% [95% CI, 61.7%-71.3%]) had a poor functional outcome, including 190 deaths (52.2%). After adjustment for non-neurological organ failure, age ≥70 years (odds ratio [OR], 2.38 [95% CI, 1.26-4.49]), Charlson comorbidity index ≥2 (OR, 2.01 [95% CI, 1.16-3.49]), a score on the Glasgow Coma Scale <8 at ICU admission (OR, 3.43 [95% CI, 1.98-5.96]), stroke subtype (intracerebral hemorrhage: OR, 2.44 [95% CI, 1.29-4.63] versus ischemic stroke: OR, 2.06 [95% CI, 1.06-4.00] versus subarachnoid hemorrhage: reference) remained independently associated with poor functional outcome. In contrast, a time between stroke diagnosis and initiation of mechanical ventilation >1 day was protective (OR, 0.56 [95% CI, 0.33-0.94]). A sensitivity analysis conducted after exclusion of patients with early decisions of withholding/withdrawal of care yielded similar results. We observed persistent physical and psychological problems at 1 year in >50% of survivors. CONCLUSIONS: In patients with severe stroke requiring mechanical ventilation, several ICU admission variables may inform caregivers, patients, and their families on post-ICU trajectories and functional outcomes. The burden of persistent sequelae at 1 year reinforces the need for a personalized, multi-disciplinary, prolonged follow-up of these patients after ICU discharge. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT03335995.

Extravascular lung water is an independent prognostic factor in patients with acute respiratory distress syndrome.

OBJECTIVE: Acute respiratory distress syndrome might be associated with an increase in extravascular lung water index and pulmonary vascular permeability index, which can be measured by transpulmonary thermodilution. We tested whether extravascular lung water index and pulmonary vascular permeability index are independent prognostic factors in patients with acute respiratory distress syndrome. DESIGN: Retrospective study. SETTING: Medical intensive care unit. PATIENTS: Two hundred consecutive acute respiratory distress syndrome patients (age = 57 ± 17, Simplified Acute Physiology Score II = 57 ± 20, overall day-28 mortality = 54%). MEASUREMENTS: Extravascular lung water index and pulmonary vascular permeability index were collected (PiCCO device, Pulsion Medical Systems) at each day of the acute respiratory distress syndrome episode. MAIN RESULTS: The maximum values of extravascular lung water index and pulmonary vascular permeability index recorded during the acute respiratory distress syndrome episode (maximum value of extravascular lung water index and maximum value of pulmonary vascular permeability index, respectively) were significantly higher in nonsurvivors than in survivors at day-28 (mean ± SD: 24 ± 10 mL/kg vs. 19 ± 7 mL/kg of predicted body weight, p < 0.001 [t-test] for maximum value of extravascular lung water index and median [interquartile range]: 4.4 [3.3-6.1] vs. 3.5 [2.8-4.4], p = 0.001 for maximum value of pulmonary vascular permeability index, Wilcoxon's test). In multivariate analyses, maximum value of extravascular lung water index or maximum value of pulmonary vascular permeability index, Simplified Acute Physiology Score II, maximum blood lactate, mean positive end-expiratory pressure, mean cumulative fluid balance, and the minimal ratio of arterial oxygen pressure over the inspired oxygen fraction were all independently associated with day-28 mortality. A maximum value of extravascular lung water index >21 mL/kg predicted day-28 mortality with a sensitivity of (mean [95% confidence interval]) 54% (44-63)% and a specificity of 73% (63-82)%. The mortality rate was 70% in patients with a maximum value of extravascular lung water index >21 mL/kg and 43% in the remaining patients (p = 0.0003). A maximum value of pulmonary vascular permeability index >3.8 predicted day-28 mortality with a sensitivity of (mean [95% confidence interval]) 67% (57-76)% and a specificity of 65% (54-75)%. The mortality rate was 69% in patients with a maximum value of pulmonary vascular permeability index >3.8 and 37% in the group with a maximum value of pulmonary vascular permeability index ≤ 3.8 (p < 0.0001). CONCLUSIONS: Extravascular lung water index and pulmonary vascular permeability index measured by transpulmonary thermodilution are independent risk factors of day-28 mortality in patients with acute respiratory distress syndrome.

Associations between teacher stress and school leadership: A mixed methods study with implications for school psychologists.

School psychologists have the psychological and consultative expertise necessary to support teachers who are vulnerable to stress. Transactional theory offers a lens to guide such support, as it posits that each teacher's unique appraisals of their work demands and resources determine the degree to which they are at risk for stress. This study used a multiphase sequential mixed method design with a transactional theory lens to examine the association of leadership quality and stability with teachers' ratings of workplace conditions. The four phases consisted of (a) input from an expert panel, (b) scale development and validation, (c) interviews with key informants, and (d) multilevel modeling informed by all previous phases. Through key informant interviews, district-level administrators provided ratings of the quality and stability of school leadership. The researchers examined the associations between these ratings and teacher appraisals of classroom demands, classroom resources, job satisfaction, and perceived levels of instructional support collected via a district-wide climate survey. Multilevel models with key informant ratings and school characteristics at Level 2 (Nschools = 47) and teacher characteristics and perceptions at Level 1 (Nteachers = 1,850) demonstrated that the quality and stability of school leadership were associated with teachers' appraisals of their occupational demands and resources, job satisfaction, and ratings of instructional support. Findings show that the quality and stability of school leadership play an important role in the incidence of stress vulnerability, suggesting important pathways for school psychologists seeking to promote the occupational health of teachers. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

The place of new antibiotics for Gram-negative bacterial infections in intensive care: report of a consensus conference.

INTRODUCTION: New beta-lactams, associated or not with beta-lactamase inhibitors (NBs/BIs), can respond to the spread of carbapenemase-producing enterobacteriales and nonfermenting carbapenem-resistant bacteria. The risk of emergence of resistance to these NBs/BIs makes guidelines necessary. The SRLF organized a consensus conference in December 2022. METHODS: An ad hoc committee without any conflict of interest (CoI) with the subject identified the molecules (ceftolozane-tazobactam, ceftazidime-avibactam, imipenem-cilastatin-relebactam, meropenem-vaborbactam and cefiderocol); defined 6 generic questions; drew up a list of subquestions according to the population, intervention, comparison and outcomes (PICO) model; and reviewed the literature using predefined keywords. The quality of the data was assessed using the GRADE methodology. Seven experts in the field proposed their own answers to the questions in a public session and answered questions from the jury (a panel of 10 critical-care physicians without any CoI) and the public. The jury then met alone for 48 h to write its recommendations. Due to the frequent lack of powerful studies that have used clinically important criteria of judgment, the recommendations were formulated as expert opinions as often as necessary. RESULTS: The jury provided 17 statements answering 6 questions: (1) Is there a place in the ICU for the probabilistic use of new NBs/IBs active against Gram-negative bacteria? (2) In the context of documented infections with sensitivity to several of these molecules, are there pharmacokinetic, pharmacodynamic, ecological or medico-economic elements for prioritization? (3) What are the possible combinations with these molecules and in what context? (4) Should we integrate these new molecules into a carbapenem-sparing strategy? (5) What pharmacokinetic and pharmacodynamic data are available to optimize their mode of administration in critically ill patients? (6) What are the dosage adaptations in cases of renal insufficiency, hepatocellular insufficiency or obesity? CONCLUSION: These recommendations should optimize the use of NBs/BIs in ICU patients.

Clinical features and maternal and fetal outcomes in women with Guillain-Barré syndrome in pregnancy.

BACKGROUND: Guillain-Barre syndrome (GBS) is an acute inflammatory polyradiculoneuropathy rarely observed during pregnancy. METHODS: In this retrospective study, we analyzed the characteristics of pregnant women with GBS (pGBS) diagnosed in French University Hospitals in the 2002-2022 period and compared them with a reference group of same-age non-pregnant women with GBS (npGBS) identified in the same institutions & timeframe. RESULTS: We identified 16 pGBS cases. Median age was 31 years (28-36), and GBS developed in the 1st, 2nd, and 3rd trimester in 31%, 31% and 38% of cases respectively. A previous infection was identified in six cases (37%), GBS was demyelinating in nine cases (56%), and four patients (25%) needed respiratory assistance. Fifteen patients (94%) were treated with intravenous immunoglobulins, and neurological recovery was complete in all cases (100%). Unscheduled caesarean section was needed in five cases (31%), and two fetuses (12.5%) died because of cytomegalovirus (CMV) infection (1 case) and HELLP (Hemolysis, Elevated Liver enzymes and Low Platelets) syndrome (1 case). In comparison with a reference group of 18 npGBS women with a median age of 30 years (27-33), pGBS patients more frequently had CMV infection (31% vs 11%), had a prolonged delay between GBS onset and hospital admission (delay > 7 days: 57% vs 12%), more often needed ICU admission (56% vs 33%) and respiratory assistance (25% vs 11%), and more often presented with treatment-related fluctuations (37% vs 0%). CONCLUSIONS: This study shows GBS during pregnancy is a severe maternal condition with significant fetal mortality.

A cost-effectiveness analysis of four approaches to universal screening for reading risk in upper elementary and middle school.

Research on universal screening in reading has primarily focused on the psychometric adequacy of screening procedures without critically considering costs and value. Educators in upper elementary and middle school have access to a great deal of extant student achievement data, which makes the evaluation of the costs associated with collecting new data for screening purposes paramount. We conducted a retrospective analysis of four approaches to reading screening using cost-effectiveness analysis. Universal screening (i.e., aimswebPlus reading) and statewide reading test data were collected in a midsize school district in Texas for 19,417 students in Grades 4-8. We analyzed the total cost, the classification accuracy based on local cut-scores derived using receiver operating characteristic analysis, and the cost-effectiveness of each approach. Full implementation of the fall administration of aimswebPlus reading cost the district $55,199 in upper elementary and $76,832 in middle school. Both the use of prior-year state achievement test data alone (which represented no additional costs for screening) and the multivariate model (i.e., prior-year state achievement test data plus aimswebPlus) met typical recommendations for classification accuracy. A multiple-gate model that used prior-year state test data and fall aimswebPlus reading on a low-achieving subset of students produced the lowest cost-effectiveness ratio at $156 per additional student accurately classified in upper elementary and $181 in middle school, but this model also led to the highest number of false negatives. The use of aimswebPlus alone resulted in the highest costs and lowest classification accuracy. The results suggest that the use of prior-year statewide achievement test data alone in Grades 4-8 is an efficient approach to universal screening for reading risk that may allow schools to shift resources from screening to other educational priorities.

Nicotine patches in patients on mechanical ventilation for severe COVID-19: a randomized, double-blind, placebo-controlled, multicentre trial.

PURPOSE: Epidemiologic studies have documented lower rates of active smokers compared to former or non-smokers in symptomatic patients affected by coronavirus disease 2019 (COVID-19). We assessed the efficacy and safety of nicotine administered by a transdermal patch in critically ill patients with COVID-19 pneumonia. METHODS: In this multicentre, double-blind, placebo-controlled trial conducted in 18 intensive care units in France, we randomly assigned adult patients (non-smokers, non-vapers or who had quit smoking/vaping for at least 12 months) with proven COVID-19 pneumonia receiving invasive mechanical ventilation for up to 72 h to receive transdermal patches containing either nicotine at a daily dose of 14 mg or placebo until 48 h following successful weaning from mechanical ventilation or for a maximum of 30 days, followed by 3-week dose tapering by 3.5 mg per week. Randomization was stratified by centre, non- or former smoker status and Sequential Organ Function Assessment score (< or ≥ 7). The primary outcome was day-28 mortality. Main prespecified secondary outcomes included 60-day mortality, time to successful extubation, days alive and free from mechanical ventilation, renal replacement therapy, vasopressor support or organ failure at day 28. RESULTS: Between November 6th 2020, and April 2nd 2021, 220 patients were randomized from 18 active recruiting centers. After excluding 2 patients who withdrew consent, 218 patients (152 [70%] men) were included in the analysis: 106 patients to the nicotine group and 112 to the placebo group. Day-28 mortality did not differ between the two groups (30 [28%] of 106 patients in the nicotine group vs 31 [28%] of 112 patients in the placebo group; odds ratio 1.03 [95% confidence interval, CI 0.57-1.87]; p = 0.46). The median number of day-28 ventilator-free days was 0 (IQR 0-14) in the nicotine group and 0 (0-13) in the placebo group (with a difference estimate between the medians of 0 [95% CI -3-7]). Adverse events likely related to nicotine were rare (3%) and similar between the two groups. CONCLUSION: In patients having developed severe COVID-19 pneumonia requiring invasive mechanical ventilation, transdermal nicotine did not significantly reduce day-28 mortality. There is no indication to use nicotine in this situation.

Arterial pressure allows monitoring the changes in cardiac output induced by volume expansion but not by norepinephrine.

OBJECTIVE: To evaluate to which extent the systemic arterial pulse pressure could be used as a surrogate of cardiac output for assessing the effects of a fluid challenge and of norepinephrine. DESIGN: Observational study. SETTING: Medical intensive care unit. PATIENTS: Patients with an acute circulatory failure who received a fluid challenge (228 patients, group 1) or in whom norepinephrine was introduced or increased (145 patients, group 2). INTERVENTIONS: We measured the systolic, diastolic, and mean arterial pressure, pulse pressure, and the transpulmonary thermodilution cardiac output before and after the therapeutic interventions. MAIN RESULTS: In group 1, the fluid challenge significantly increased cardiac output by 24% ± 25%. It significantly increased cardiac output by ≥15% (+35% ± 27%) in 142 patients ("responders"). The fluid-induced changes in cardiac output were correlated with the changes in pulse pressure (r = .56, p < .0001), systolic arterial pressure (r = .55, p < .0001), diastolic arterial pressure (r = .37, p < .0001), and mean arterial pressure (r = .52, p < .0001). At multivariate analysis, changes in pulse pressure were significantly related to changes in stroke volume (multiple r = .52) and to age (r = .12). A fluid-induced increase in pulse pressure of ≥17% allowed detecting a fluid-induced increase in cardiac output of ≥15% with a sensitivity of 65[56-72]% and a specificity of 85[76-92]%. The area under the receiver operating characteristic curves for the fluid-induced changes in mean arterial pressure and in diastolic arterial pressure was significantly lower than for pulse pressure. In group 2, the introduction/increase of norepinephrine significantly increased cardiac output by 14% ± 18%. The changes in cardiac output induced by the introduction/increase in the dose of norepinephrine were correlated with the changes in pulse pressure and systolic arterial pressure (r = .21 and .29, respectively, p = .001) but to a significantly lesser extent than in group 1. CONCLUSIONS: Pulse pressure and systolic arterial pressure could be used for detecting the fluid-induced changes in cardiac output, in spite of a significant proportion of false-negative cases. By contrast, the changes in pulse pressure and systolic arterial pressure were unable to detect the changes in cardiac output induced by norepinephrine.

Acute respiratory failure in kidney transplant recipients: a multicenter study.

INTRODUCTION: Data on pulmonary complications in renal transplant recipients are scarce. The aim of this study was to evaluate acute respiratory failure (ARF) in renal transplant recipients. METHODS: We conducted a retrospective observational study in nine transplant centers of consecutive kidney transplant recipients admitted to the intensive care unit (ICU) for ARF from 2000 to 2008. RESULTS: Of 6,819 kidney transplant recipients, 452 (6.6%) required ICU admission, including 200 admitted for ARF. Fifteen (7.5%) of these patients had combined kidney-pancreas transplantations. The most common causes of ARF were bacterial pneumonia (35.5%), cardiogenic pulmonary edema (24.5%) and extrapulmonary acute respiratory distress syndrome (ARDS) (15.5%). Pneumocystis pneumonia occurred in 11.5% of patients. Mechanical ventilation was used in 93 patients (46.5%), vasopressors were used in 82 patients (41%) and dialysis was administered in 104 patients (52%). Both the in-hospital and 90-day mortality rates were 22.5%. Among the 155 day 90 survivors, 115 patients (74.2%) were dialysis-free, including 75 patients (65.2%) who recovered prior renal function. Factors independently associated with in-hospital mortality were shock at admission (odds ratio (OR) 8.70, 95% confidence interval (95% CI) 3.25 to 23.29), opportunistic fungal infection (OR 7.08, 95% CI 2.32 to 21.60) and bacterial infection (OR 2.53, 95% CI 1.07 to 5.96). Five factors were independently associated with day 90 dialysis-free survival: renal Sequential Organ Failure Assessment (SOFA) score on day 1 (OR 0.68/SOFA point, 95% CI 0.52 to 0.88), bacterial infection (OR 0.43, 95% CI 0.21 to 0.90), three or four quadrants involved on chest X-ray (OR 0.44, 95% CI 0.21 to 0.91), time from hospital to ICU admission (OR 0.98/day, 95% CI 0.95 to 0.99) and oxygen flow at admission (OR 0.93/liter, 95% CI 0.86 to 0.99). CONCLUSIONS: In kidney transplant recipients, ARF is associated with high mortality and graft loss rates. Increased Pneumocystis and bacterial prophylaxis might improve these outcomes. Early ICU admission might prevent graft loss.

Hemodynamic impact of a positive end-expiratory pressure setting in acute respiratory distress syndrome: importance of the volume status.

OBJECTIVE: The hemodynamic impact of positive end-expiratory pressure in acute respiratory distress syndrome and the underlying mechanisms have not been extensively investigated during low stretch ventilation. Our aim was to evaluate the hemodynamic effect of increasing positive end-expiratory pressure when tidal volume and the plateau pressure are limited and to explore the underlying mechanisms. DESIGN: Prospective study. SETTING: Medical intensive care unit. PATIENTS: Twenty-one acute respiratory distress syndrome patients ventilated with a tidal volume of 6.0 +/- 0.5 mL/kg of predicted body weight. INTERVENTION: Positive end-expiratory pressure was significantly increased from 5 +/- 1 cm H2O to 13 +/- 4 cm H2O for reaching a plateau pressure of 30 +/- 1 cm H2O. At high positive end-expiratory pressure, passive leg raising was performed for increasing the central blood volume. MEASUREMENTS: We performed echocardiography and pulmonary artery catheterization during positive end-expiratory pressure increase and during passive leg raising at high positive end-expiratory pressure. MAIN RESULTS: With positive end-expiratory pressure elevation, the cardiac index decreased by 13% +/- 9%. The right ventricular end-diastolic area, right atrial pressure, and pulmonary vascular resistance increased by 13% +/- 20%, 34% +/- 24% and 32% +/- 31%, respectively (p < .01; p = .04; and p < .01 vs. baseline, respectively). The transpulmonary pressure difference (mean pulmonary artery pressure--pulmonary artery occlusion pressure) increased (p < .05). Both at low and high positive end-expiratory pressure, an acute cor pulmonale was observed in the same three (14%) patients. At high positive end-expiratory pressure, the passive leg raising significantly increased the right and left ventricular end-diastolic areas and right atrial pressure. Passive leg raising also decreased the transpulmonary pressure difference (p < .05), increased the cardiac index by 14% +/- 10%, and decreased the pulmonary vascular resistance by 21% +/- 20% (both p < .01 vs. baseline). CONCLUSIONS: In acute respiratory distress syndrome patients, a positive end-expiratory pressure increase with limited tidal volume and plateau pressure reduced cardiac output by increasing the right ventricular afterload. Passive leg raising restored cardiac output by reducing the transpulmonary pressure difference and the pulmonary vascular resistance. This suggests that some pulmonary microvessels were collapsed by positive end-expiratory pressure elevation and were recruited by increasing the central blood volume.

Predicting volume responsiveness by using the end-expiratory occlusion in mechanically ventilated intensive care unit patients.

OBJECTIVE: During mechanical ventilation, inspiration cyclically decreases the left cardiac preload. Thus, an end-expiratory occlusion may prevent the cyclic impediment in left cardiac preload and may act like a fluid challenge. We tested whether this could serve as a functional test for fluid responsiveness in patients with circulatory failure. DESIGN: Prospective study. SETTING: Medical intensive care unit. PATIENTS: Thirty-four mechanically ventilated patients with shock in whom volume expansion was planned. INTERVENTION: A 15-second end-expiratory occlusion followed by a 500 mL saline infusion. MEASUREMENTS: Arterial pressure and pulse contour-derived cardiac index (PiCCOplus) at baseline, during passive leg raising (PLR), during the 5-last seconds of the end-expiratory occlusion, and after volume expansion. MAIN RESULTS: Volume expansion increased cardiac index by >15% (2.4 +/- 1.0 to 3.3 +/- 1.2 L/min/m, p < 0.05) in 23 patients ("responders"). Before volume expansion, the end-expiratory occlusion significantly increased arterial pulse pressure by 15% +/- 15% and cardiac index by 12% +/- 11% in responders whereas arterial pulse pressure and cardiac index did not change significantly in nonresponders. Fluid responsiveness was predicted by an increase in pulse pressure >or=5% during the end-expiratory occlusion with a sensitivity and a specificity of 87% and 100%, respectively, and by an increase in cardiac index >or=5% during the end-expiratory occlusion with a sensitivity and a specificity of 91% and 100%, respectively. The response of pulse pressure and cardiac index to the end-expiratory occlusion predicted fluid responsiveness with an accuracy that was similar to the response of cardiac index to PLR and that was significantly better than the response of pulse pressure to PLR (receiver operating characteristic curves area 0.957 [95% confidence interval [CI:] 0.825-0.994], 0.972 [95% CI: 0.849-0.995], 0.937 [95% CI: 0.797-0.990], and 0.675 [95% CI: 0.497-0.829], respectively). CONCLUSIONS: The hemodynamic response to an end-expiratory occlusion can predict volume responsiveness in mechanically ventilated patients.

Echocardiographic diagnosis of pulmonary artery occlusion pressure elevation during weaning from mechanical ventilation.

OBJECTIVE: Weaning-induced pulmonary edema is a cause of weaning failure in high-risk patients. The diagnosis may require pulmonary artery catheterization to demonstrate increased pulmonary artery occlusion pressure (PAOP) during weaning. Transthoracic echocardiography can estimate left ventricular filling pressures using early (E) and late (A) peak diastolic velocities measured with Doppler transmitral flow, and tissue Doppler imaging of mitral annulus velocities including early (Ea) peak diastolic velocity. We tested the hypothesis that E/A and E/Ea could be used to detect weaning-induced PAOP elevation defined by a PAOP > or =18 mm Hg during a spontaneous breathing trial (SBT). MEASUREMENTS AND MAIN RESULTS: We included 39 patients who previously failed two consecutive SBTs. A third SBT was performed over a maximum 1-hour period using a T-piece. The PAOP, E/A, and E/Ea were measured before and during this SBT. Receiver operating characteristic curves were constructed to determine the optimal sensitivity and specificity values of E/A and E/Ea obtained at the end of the SBT for predicting a weaning-induced PAOP elevation. Weaning-induced PAOP elevation occurred in 17 patients. A value of E/A >0.95 at the end of the SBT predicted weaning-induced PAOP elevation with a sensitivity of 88% and a specificity of 68%. A value of E/Ea >8.5 at the end of the SBT predicted weaning-induced PAOP elevation with a sensitivity of 94% and a specificity of 73%. The combination of E/A >0.95 and E/Ea >8.5 predicted a weaning-induced PAOP elevation with a sensitivity of 82% and a specificity of 91%. CONCLUSION: At the end of an SBT, the combination of E/A >0.95 and E/Ea >8.5 measured with transthoracic echocardiography allowed an accurate noninvasive detection of weaning-induced PAOP elevation.

Severe leptospirosis in non-tropical areas: a nationwide, multicentre, retrospective study in French ICUs.

PURPOSE: To report the incidence, risk factors, clinical presentation, and outcome predictors of severe leptospirosis requiring intensive care unit (ICU) admission in a temperate zone. METHODS: LEPTOREA was a retrospective multicentre study conducted in 79 ICUs in metropolitan France. Consecutive adults admitted to the ICU for proven severe leptospirosis from January 2012 to September 2016 were included. Multiple correspondence analysis (MCA) and hierarchical classification on principal components (HCPC) were performed to distinguish different clinical phenotypes. RESULTS: The 160 included patients (0.04% of all ICU admissions) had median values of 54 years [38-65] for age, 40 [28-58] for the SAPSII, and 11 [8-14] for the SOFA score. Hospital mortality was 9% and was associated with older age; worse SOFA score and early need for endotracheal ventilation and/or renal replacement therapy; chronic alcohol abuse and worse hepatic dysfunction; confusion; and higher leucocyte count. Four phenotypes were identified: moderately severe leptospirosis (n = 34, 21%) with less organ failure and better outcomes; hepato-renal leptospirosis (n = 101, 63%) with prominent liver and kidney dysfunction; neurological leptospirosis (n = 8, 5%) with the most severe organ failures and highest mortality; and respiratory leptospirosis (n = 17, 11%) with pulmonary haemorrhage. The main risk factors for leptospirosis contamination were contact with animals, contact with river or lake water, and specific occupations. CONCLUSIONS: Severe leptospirosis was an uncommon reason for ICU admission in metropolitan France and carried a lower mortality rate than expected based on the high severity and organ-failure scores. The identification in our population of several clinical presentations may help clinicians establish an appropriate index of suspicion for severe leptospirosis.

Effects of changes in vascular tone on the agreement between pulse contour and transpulmonary thermodilution cardiac output measurements within an up to 6-hour calibration-free period.

OBJECTIVES: To examine whether the agreement between pulse contour and transpulmonary thermodilution cardiac index (CI) measurements is altered by changes in vascular tone within an up to 6-hr calibration-free period. DESIGN: Observational study. SETTING: Medical intensive care unit of a university hospital. PATIENTS: Fifty-nine critically ill patients. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Data from 59 critically ill patients equipped with a PiCCO device were retrospectively analyzed. The database contained the transpulmonary thermodilution CI (CI(T)) value obtained at each time point the device was calibrated and the pulse contour CI (CI(PC)) value recorded immediately before this time point. Seven subsets of CI pairs were defined according to intervals of time elapsed from the previous calibration (within the first 30 mins, between 30 mins and 1 hr, and every hour up to 6 hrs). In the whole set of 400 CI pairs, CI(PC) correlated with CI(T) (r2 = .68, p < .001). The bias +/- SD was 0.12 +/- 0.61 L/min/m2, and the percentage error was 35%. Among the seven time-interval subsets, the percentage error was <30% only in the two first ones (27% and 26%, respectively). When changes in systemic vascular resistance by >15% occurred (129 times), CI(PC) correlated with CI(T) (r2 = .64), the bias +/- SD was 0.12 +/- 0.62 L/min/m2, and the percentage error was 36%. In the subset of CI pairs recorded within the 1-hr calibration-free period while vascular resistance changed by >15% (n = 32), the bias +/- SD was 0.04 +/- 0.47 L/min/m and the percentage error was 29%. CONCLUSIONS: Our study in critically ill patients suggests that the agreement between pulse contour cardiac output and transpulmonary thermodilution cardiac output was not significantly influenced by changes in vascular tone. However, after a 1-hr calibration-free period, recalibration may be encouraged. Such a procedure provides helpful information drawn from other thermodilution-derived variables.

Increase in plasma protein concentration for diagnosing weaning-induced pulmonary oedema.

OBJECTIVE: Weaning-induced cardiogenic pulmonary oedema is a cause of weaning failure that is classically diagnosed by an increase in pulmonary artery occlusion pressure during a spontaneous breathing trial. During cardiogenic pulmonary oedema, a hypo-oncotic fluid is filtered toward the interstitial space. Thus, we tested whether the changes in plasma protein concentration during a weaning trial could diagnose weaning-induced pulmonary oedema. DESIGN: Prospective study. SETTING: The 24-bed medical intensive care unit of a university hospital. PATIENTS: Forty-six patients who had failed two weaning trials. INTERVENTION: Weaning-induced pulmonary oedema was diagnosed if a respiratory failure associated with an increase in pulmonary artery occlusion pressure above 18 mmHg occurred during a third weaning trial on a T-tube. The plasma protein concentration was measured before and at the end of the spontaneous breathing trial. MEASUREMENTS AND RESULTS: During the weaning trial, pulmonary oedema was observed in 24 patients. In these patients, the plasma protein concentration increased by 11% (3-25%). The plasma protein concentration did not change significantly in patients who did not experience weaning-induced pulmonary oedema. An increase in the plasma protein concentration greater than 6% from baseline to the end of the weaning trial allowed detecting a weaning-induced pulmonary oedema with a sensitivity of 87% and a specificity of 95%. CONCLUSION: The acute changes in plasma protein concentration during a weaning trial represent an alternative method to right heart catheterisation for assessing weaning-induced pulmonary oedema.

Critical care management and outcome of severe Pneumocystis pneumonia in patients with and without HIV infection.

BACKGROUND: Little is known about the most severe forms of Pneumocystis jiroveci pneumonia (PCP) in HIV-negative as compared with HIV-positive patients. Improved knowledge about the differential characteristics and management modalities could guide treatment based on HIV status. METHODS: We retrospectively compared 72 patients (73 cases, 46 HIV-positive) admitted for PCP from 1993 to 2006 in the intensive care unit (ICU) of a university hospital. RESULTS: The yearly incidence of ICU admissions for PCP in HIV-negative patients increased from 1993 (0%) to 2006 (6.5%). At admission, all but one non-HIV patient were receiving corticosteroids. Twenty-three (85%) HIV-negative patients were receiving an additional immunosuppressive treatment. At admission, HIV-negative patients were significantly older than HIV-positive patients (64 [18 to 82] versus 37 [28 to 56] years old) and had a significantly higher Simplified Acute Physiology Score (SAPS) II (38 [13 to 90] versus 27 [11 to 112]) but had a similar PaO2/FiO2 (arterial partial pressure of oxygen/fraction of inspired oxygen) ratio (160 [61 to 322] versus 183 [38 to 380] mm Hg). Ventilatory support was required in a similar proportion of HIV-negative and HIV-positive cases (78% versus 61%), with a similar proportion of first-line non-invasive ventilation (NIV) (67% versus 54%). NIV failed in 71% of HIV-negative and in 13% of HIV-positive patients (p < 0.01). Mortality was significantly higher in HIV-negative than HIV-positive cases (48% versus 17%). The HIV-negative status (odds ratio 3.73, 95% confidence interval 1.10 to 12.60) and SAPS II (odds ratio 1.07, 95% confidence interval 1.02 to 1.12) were independently associated with mortality at multivariate analysis. CONCLUSION: The yearly incidence of ICU admissions for PCP in HIV-negative patients in our unit increased from 1993 to 2006. The course of the disease and the outcome were worse in HIV-negative patients. NIV often failed in HIV-negative cases, suggesting that NIV must be watched closely in this population.

Positive end-expiratory pressure setting in adults with acute lung injury and acute respiratory distress syndrome: a randomized controlled trial.

CONTEXT: The need for lung protection is universally accepted, but the optimal level of positive end-expiratory pressure (PEEP) in patients with acute lung injury (ALI) or acute respiratory distress syndrome remains debated. OBJECTIVE: To compare the effect on outcome of a strategy for setting PEEP aimed at increasing alveolar recruitment while limiting hyperinflation to one aimed at minimizing alveolar distension in patients with ALI. DESIGN, SETTING, AND PATIENTS: A multicenter randomized controlled trial of 767 adults (mean [SD] age, 59.9 [15.4] years) with ALI conducted in 37 intensive care units in France from September 2002 to December 2005. INTERVENTION: Tidal volume was set at 6 mL/kg of predicted body weight in both strategies. Patients were randomly assigned to a moderate PEEP strategy (5-9 cm H(2)O) (minimal distension strategy; n = 382) or to a level of PEEP set to reach a plateau pressure of 28 to 30 cm H(2)O (increased recruitment strategy; n = 385). MAIN OUTCOME MEASURES: The primary end point was mortality at 28 days. Secondary end points were hospital mortality at 60 days, ventilator-free days, and organ failure-free days at 28 days. RESULTS: The 28-day mortality rate in the minimal distension group was 31.2% (n = 119) vs 27.8% (n = 107) in the increased recruitment group (relative risk, 1.12 [95% confidence interval, 0.90-1.40]; P = .31). The hospital mortality rate in the minimal distension group was 39.0% (n = 149) vs 35.4% (n = 136) in the increased recruitment group (relative risk, 1.10 [95% confidence interval, 0.92-1.32]; P = .30). The increased recruitment group compared with the minimal distension group had a higher median number of ventilator-free days (7 [interquartile range {IQR}, 0-19] vs 3 [IQR, 0-17]; P = .04) and organ failure-free days (6 [IQR, 0-18] vs 2 [IQR, 0-16]; P = .04). This strategy also was associated with higher compliance values, better oxygenation, less use of adjunctive therapies, and larger fluid requirements. CONCLUSIONS: A strategy for setting PEEP aimed at increasing alveolar recruitment while limiting hyperinflation did not significantly reduce mortality. However, it did improve lung function and reduced the duration of mechanical ventilation and the duration of organ failure. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00188058.

Assessing pulmonary permeability by transpulmonary thermodilution allows differentiation of hydrostatic pulmonary edema from ALI/ARDS.

OBJECTIVE: To test whether assessing pulmonary permeability by transpulmonary thermodilution enables to differentiate increased permeability pulmonary edema (ALI/ARDS) from hydrostatic pulmonary edema. DESIGN: Retrospective review of cases. SETTING: A 24-bed medical intensive care unit of a university hospital. PATIENTS: Forty-eight critically ill patients ventilated for acute respiratory failure with bilateral infiltrates on chest radiograph, a PaO(2)/FiO(2) ratio < 300 mmHg and extravascular lung water indexed for body weight >/= 12 ml/kg. INTERVENTION: We assessed pulmonary permeability by two indexes obtained from transpulmonary thermodilution: extravascular lung water/pulmonary blood volume (PVPI) and the ratio of extravascular lung water index over global end-diastolic volume index. The cause of pulmonary edema was determined a posteriori by three experts, taking into account medical history, clinical features, echocardiographic left ventricular function, chest radiography findings, B-type natriuretic peptide serum concentration and the time-course of these findings with therapy. Experts were blind for pulmonary permeability indexes and for global end-diastolic volume. MEASUREMENTS AND RESULTS: ALI/ARDS was diagnosed in 36 cases. The PVPI was 4.7+/-1.8 and 2.1+/-0.5 in patients with ALI/ARDS and hydrostatic pulmonary edema, respectively (p<0.05). The extravascular lung water index/global end-diastolic volume index ratio was 3.0 x 10(-2)+/-1.2 x 10(-2) and 1.4 x 10(-2)+/-0.4 x 10(-2) in patients with ALI/ARDS and with hydrostatic pulmonary edema, respectively (p<0.05). A PVPI >/= 3 and an extravascular lung water index/global end-diastolic index ratio >/= 1.8 x 10(-2) allowed the diagnosis of ALI/ARDS with a sensitivity of 85% and specificity of 100%. CONCLUSION: These results suggest that indexes of pulmonary permeability provided by transpulmonary thermodilution may be useful for determining the mechanism of pulmonary edema in the critically ill.

Contribution of arterial stiffness and stroke volume to peripheral pulse pressure in ICU patients: an arterial tonometry study.

OBJECTIVE: Peripheral arterial pulse pressure is increasingly used to assess hemodynamic status. Our aim was to test the respective influence of arterial stiffness, stroke volume, peripheral resistance, and various hemodynamic and demographic variables on peripheral pulse pressure in critically ill patients. DESIGN: Prospective study. SETTING: Medical intensive care unit of a university hospital. INTERVENTIONS: None. PATIENTS: 67 sinus rhythm patients (mean age 57+/-17 years) of whom 17 received vasoactive agents. MEASUREMENTS AND RESULTS: The stroke volume was calculated by Doppler echocardiography. Radial pressures were calibrated from systolic and diastolic brachial cuff pressures. Central aortic pressure was estimated by radial applanation tonometry. The arterial compliance was estimated from the aortic pressure curve using the area method and the arterial stiffness was calculated as 1/compliance. The influences of age, body surface area, arterial stiffness, stroke volume, peripheral resistance, and time intervals on peripheral pulse pressure were tested using univariate and multivariate analyses. The mean arterial pressure ranged from 42 to 113 mmHg. Peripheral pulse pressure (59+/-17 mmHg) was higher than aortic pulse pressure (40+/-14 mmHg, p<0.001). In patients aged >or= 60 years whose mean arterial pressure was >or= 80 mmHg, peripheral pulse pressure was related to arterial stiffness (r2=0.41) and to stroke volume (multiple r2 =0.90). A similar but weaker relationship was observed in the overall population (multiple r2=0.52). CONCLUSIONS: In critically ill patients, and especially in aged subjects with hemodynamic stability, peripheral pulse pressure mainly reflected the combined influences of arterial stiffness and stroke volume.