Low versus standard calorie and protein feeding in ventilated adults with shock: a randomised, controlled, multicentre, open-label, parallel-group trial (NUTRIREA-3).

BACKGROUND: The optimal calorie and protein intakes at the acute phase of severe critical illness remain unknown. We hypothesised that early calorie and protein restriction improved outcomes in these patients, compared with standard calorie and protein targets. METHODS: The pragmatic, randomised, controlled, multicentre, open-label, parallel-group NUTRIREA-3 trial was performed in 61 French intensive care units (ICUs). Adults (≥18 years) receiving invasive mechanical ventilation and vasopressor support for shock were randomly assigned to early nutrition (started within 24 h after intubation) with either low or standard calorie and protein targets (6 kcal/kg per day and 0·2-0·4 g/kg per day protein vs 25 kcal/kg per day and 1·0-1·3 g/kg per day protein) during the first 7 ICU days. The two primary endpoints were time to readiness for ICU discharge and day 90 all-cause mortality. Key secondary outcomes included secondary infections, gastrointestinal events, and liver dysfunction. The trial is registered on ClinicalTrials.gov, NCT03573739, and is completed. FINDINGS: Of 3044 patients randomly assigned between July 5, 2018, and 8 Dec 8, 2020, eight withdrew consent to participation. By day 90, 628 (41·3%) of 1521 patients in the low group and 648 (42·8%) of 1515 patients in the standard group had died (absolute difference -1·5%, 95% CI -5·0 to 2·0; p=0·41). Median time to readiness for ICU discharge was 8·0 days (IQR 5·0-14·0) in the low group and 9·0 days (5·0-17·0) in the standard group (hazard ratio [HR] 1·12, 95% CI 1·02 to 1·22; p=0·015). Proportions of patients with secondary infections did not differ between the groups (HR 0·85, 0·71 to 1·01; p=0·06). The low group had lower proportions of patients with vomiting (HR 0·77, 0·67 to 0·89; p<0·001), diarrhoea (0·83, 0·73 to 0·94; p=0·004), bowel ischaemia (0·50, 0·26 to 0·95; p=0·030), and liver dysfunction (0·92, 0·86-0·99; p=0·032). INTERPRETATION: Compared with standard calorie and protein targets, early calorie and protein restriction did not decrease mortality but was associated with faster recovery and fewer complications. FUNDING: French Ministry of Health.

Factors associated with acute mesenteric ischemia among critically ill ventilated patients with shock: a post hoc analysis of the NUTRIREA2 trial.

PURPOSE: Acute mesenteric ischemia (AMI) is a rare, but life-threatening condition occurring among critically ill patients. Several factors have been associated with AMI, but the causal link is debated, most studies being retrospective. Among these factors, enteral nutrition (EN) could be associated with AMI, in particular among patients with shock. We aimed to study the factors independently associated with AMI in a post hoc analysis of the NUTRIREA-2 trial including 2410 critically ill ventilated patients with shock, randomly assigned to receive EN or parenteral nutrition (PN). METHODS: Post hoc analysis of the NUTRIREA-2 trial was conducted. Ventilated adults with shock were randomly assigned to receive EN or PN. AMI was assessed by computed tomography, endoscopy, or laparotomy. Factors associated with AMI were studied by univariate and multivariate analysis. RESULTS: 2410 patients from 44 French intensive care units (ICUs) were included in the study: 1202 patients in the enteral group and 1208 patients in the parenteral group. The median age was 67 [58-76] years, with 67% men, a SAPS II score of 59 [46-74], and a medical cause for ICU admission in 92.7%. AMI was diagnosed among 24 (1%) patients, mainly by computed tomography (79%) or endoscopy (38%). The mechanism of AMI was non-occlusive mesenteric ischemia (n = 12), occlusive (n = 4), and indeterminate (n = 8). The median duration between inclusion in the trial and AMI diagnosis was 4 [1-11] days. Patients with AMI were older, had a higher SAPS II score at ICU admission, had higher plasma lactate, creatinine, and ASAT concentrations and lower hemoglobin concentration, had more frequently EN, dobutamine, and CVVHDF at inclusion, developed more frequently bacteremia during ICU stay, and had higher 28-day and 90-day mortality rates compared with patients without AMI. By multivariate analysis, AMI was independently associated with EN, dobutamine use, SAPS II score ≥ 62 and hemoglobin concentration ≤ 10.9 g/dL. CONCLUSION: Among critically ill ventilated patients with shock, EN, dobutamine use, SAPS II score ≥ 62 and hemoglobin ≤ 10.9 g/dL were independently associated with AMI. Among critically ill ventilated patients requiring vasopressors, EN should be delayed or introduced cautiously in case of low cardiac output requiring dobutamine and/or in case of multiple organ failure with high SAPS II score.

Impact of early low-calorie low-protein versus standard-calorie standard-protein feeding on outcomes of ventilated adults with shock: design and conduct of a randomised, controlled, multicentre, open-label, parallel-group trial (NUTRIREA-3).

INTRODUCTION: International guidelines include early nutritional support (≤48 hour after admission), 20-25 kcal/kg/day, and 1.2-2 g/kg/day protein at the acute phase of critical illness. Recent data challenge the appropriateness of providing standard amounts of calories and protein during acute critical illness. Restricting calorie and protein intakes seemed beneficial, suggesting a role for metabolic pathways such as autophagy, a potential key mechanism in safeguarding cellular integrity, notably in the muscle, during critical illness. However, the optimal calorie and protein supply at the acute phase of severe critical illness remains unknown. NUTRIREA-3 will be the first trial to compare standard calorie and protein feeding complying with guidelines to low-calorie low-protein feeding. We hypothesised that nutritional support with calorie and protein restriction during acute critical illness decreased day 90 mortality and/or dependency on intensive care unit (ICU) management in mechanically ventilated patients receiving vasoactive amine therapy for shock, compared with standard calorie and protein targets. METHODS AND ANALYSIS: NUTRIREA-3 is a randomised, controlled, multicentre, open-label trial comparing two parallel groups of patients receiving invasive mechanical ventilation and vasoactive amine therapy for shock and given early nutritional support according to one of two strategies: early calorie-protein restriction (6 kcal/kg/day-0.2-0.4 g/kg/day) or standard calorie-protein targets (25 kcal/kg/day, 1.0-1.3 g/kg/day) at the acute phase defined as the first 7 days in the ICU. We will include 3044 patients in 61 French ICUs. Two primary end-points will be evaluated: day 90 mortality and time to ICU discharge readiness. The trial will be considered positive if significant between-group differences are found for one or both alternative primary endpoints. Secondary outcomes include hospital-acquired infections and nutritional, clinical and functional outcomes. ETHICS AND DISSEMINATION: The NUTRIREA-3 study has been approved by the appropriate ethics committee. Patients are included after informed consent. Results will be submitted for publication in peer-reviewed journals. TRIAL REGISTRATION NUMBER: NCT03573739.

High-flow nasal cannula therapy: clinical practice in intensive care units.

BACKGROUND: Despite the extensive use of high-flow nasal cannula (HFNC) therapy in intensive care units (ICU) for acute respiratory failure (ARF), its daily clinical practice has not been assessed. We designed a regional survey in ICUs in North-west France to evaluate ICU physicians' clinical practice with HFNC. MATERIALS AND METHODS: We sent an observational survey to ICU physicians from 34 French ICUs over a 6-month period in 2016-2017. The survey included questions regarding the indications and expected efficiency of HFNC, practical aspects of use (initiation, weaning) and satisfaction. Comparisons between junior and senior ICU physicians were performed using a Fischer exact test. RESULTS: Among the 235 ICU physicians contacted, 137 responded (58.3%) all of whom regularly used HFNC. Hypoxemic ARF was considered a good indication for HFNC by all 137, but only 30% expected HFNC success (i.e., avoiding intubation in at least 60% of cases). Among hypoxemic indications, 30% of juniors considered acute pulmonary edema a good indication versus 74% of seniors (p < 0.0001). Hypercapnic ARF was considered a good indication by 33% with only 2% expecting HFNC success. A need for conventional oxygen therapy ≥ 6 L/min justified HFNC therapy for 40% and ≥ 9 L/min for 39% of responders. 58% of ICU physicians started HFNC therapy with a FiO2 ≥ 50% and 28% with a gas flow ≥ 50 L/min. Practices for HFNC weaning were heterogeneous: 48% considered a FiO2 ≤ 30%; whereas, 30% considered a FiO2 ≤ 30% with a high flow ≤ 20 L/min. Criteria for HFNC failure (i.e., need for intubation) were ventilatory pauses or arrest (97%), persistent hypoxemia (95%), respiratory acidosis (81%), worsening of breathing (95%, 100% of seniors and 86% of juniors, p = 0.003), bronchial congestion (75%) and circulatory failure (61%, 72% of seniors and 44% of juniors, p = 0.007). CONCLUSION: HFNC is used by ICU physicians in many situations of ARF, despite their relatively low expectations of success, especially in cases of hypercapnia. Clinical practices appear somewhat heterogeneous. Despite the physiological benefit of HFNC, further prospective observational studies are still required on HFNC outcomes and daily practices.

Enteral versus parenteral early nutrition in ventilated adults with shock: a randomised, controlled, multicentre, open-label, parallel-group study (NUTRIREA-2).

BACKGROUND: Whether the route of early feeding affects outcomes of patients with severe critical illnesses is controversial. We hypothesised that outcomes were better with early first-line enteral nutrition than with early first-line parenteral nutrition. METHODS: In this randomised, controlled, multicentre, open-label, parallel-group study (NUTRIREA-2 trial) done at 44 French intensive-care units (ICUs), adults (18 years or older) receiving invasive mechanical ventilation and vasopressor support for shock were randomly assigned (1:1) to either parenteral nutrition or enteral nutrition, both targeting normocaloric goals (20-25 kcal/kg per day), within 24 h after intubation. Randomisation was stratified by centre using permutation blocks of variable sizes. Given that route of nutrition cannot be masked, blinding of the physicians and nurses was not feasible. Patients receiving parenteral nutrition could be switched to enteral nutrition after at least 72 h in the event of shock resolution (no vasopressor support for 24 consecutive hours and arterial lactate <2 mmol/L). The primary endpoint was mortality on day 28 after randomisation in the intention-to-treat-population. This study is registered with ClinicalTrials.gov, number NCT01802099. FINDINGS: After the second interim analysis, the independent Data Safety and Monitoring Board deemed that completing patient enrolment was unlikely to significantly change the results of the trial and recommended stopping patient recruitment. Between March 22, 2013, and June 30, 2015, 2410 patients were enrolled and randomly assigned; 1202 to the enteral group and 1208 to the parenteral group. By day 28, 443 (37%) of 1202 patients in the enteral group and 422 (35%) of 1208 patients in the parenteral group had died (absolute difference estimate 2·0%; [95% CI -1·9 to 5·8]; p=0·33). Cumulative incidence of patients with ICU-acquired infections did not differ between the enteral group (173 [14%]) and the parenteral group (194 [16%]; hazard ratio [HR] 0·89 [95% CI 0·72-1·09]; p=0·25). Compared with the parenteral group, the enteral group had higher cumulative incidences of patients with vomiting (406 [34%] vs 246 [20%]; HR 1·89 [1·62-2·20]; p<0·0001), diarrhoea (432 [36%] vs 393 [33%]; 1·20 [1·05-1·37]; p=0·009), bowel ischaemia (19 [2%] vs five [<1%]; 3·84 [1·43-10·3]; p=0·007), and acute colonic pseudo-obstruction (11 [1%] vs three [<1%]; 3·7 [1·03-13·2; p=0·04). INTERPRETATION: In critically ill adults with shock, early isocaloric enteral nutrition did not reduce mortality or the risk of secondary infections but was associated with a greater risk of digestive complications compared with early isocaloric parenteral nutrition. FUNDING: La Roche-sur-Yon Departmental Hospital and French Ministry of Health.

Practice of ultrasound-guided central venous catheter technique by the French intensivists: a survey from the BoReal study group.

BACKGROUND: The ultrasound (US)-guided technique has been recommended for central venous catheter (CVC) placement in critical care. However, several surveys have shown that the majority of physicians continue to perform landmark procedures. In our region, we have implemented special courses to promote the use of US with formal training and simulators. Ultrasound machines have also been installed in almost every ICU in our area. We designed a survey to investigate whether the training program established for years and the widespread of ultrasound devices in the ICU of our region will be associated with a high rate of physicians performing US procedures. METHODS: A survey comprising 14 questions was designed to elicit information on training in US techniques, the use of US for CVC placement, reasons for nonuse of US and their opinion concerning the need to teach the landmark technique to residents. This survey was electronically sent to every physician of the BoReal study group (32 ICUs located in the North West of France). RESULTS: We received 190 responses (response rate 66 %) including 34 % of residents. Only 11 % of respondents reported the absence of training in the US technique, and 3 % reported they did not have access to an ultrasound machine. A total of 68 % declared "always" (18 %) or "almost always" (50 %) using US to guide CVC placement. Our results are better than those of previous surveys. The main reasons why physicians did not use the US technique were that they thought that US guidance was unnecessary (36 %) or because the ultrasound machine was not immediately available (33 %). Ninety-one percentages think that the landmark technique should still be taught to the residents. A higher proportion of residents compared to seniors declared that they always or almost always used the US technique. CONCLUSION: Training in ultrasound techniques and the widespread availability of ultrasound machines in ICUs seem to improve the rate of US procedures. However, despite strong scientific evidence a proportion of physicians continue to consider the landmark technique as an alternative to US. Training and education are potentially still the best ways to overcome such barriers or conviction.

Comparison of two strategies for initiating renal replacement therapy in the intensive care unit: study protocol for a randomized controlled trial (AKIKI).

BACKGROUND: There is currently no validated strategy for the timing of renal replacement therapy (RRT) for acute kidney injury (AKI) in the intensive care unit (ICU) when short-term life-threatening metabolic abnormalities are absent. No adequately powered prospective randomized study has addressed this issue to date. As a result, significant practice heterogeneity exists and may expose patients to either unnecessary hazardous procedures or undue delay in RRT. METHODS/DESIGN: This is a multicenter, prospective, randomized, open-label parallel-group clinical trial that compares the effect of two RRT initiation strategies on overall survival of critically ill patients receiving intravenous catecholamines or invasive mechanical ventilation and presenting with AKI classification stage 3 (KDIGO 2012). In the 'early' strategy, RRT is initiated immediately. In the 'delayed' strategy, clinical and metabolic conditions are closely monitored and RRT is initiated only when one or more events (severity criteria) occur, including: oliguria or anuria for more than 72 hours after randomization, serum urea concentration >40 mmol/l, serum potassium concentration >6 mmol/l, serum potassium concentration >5.5 mmol/l persisting despite medical treatment, arterial blood pH <7.15 in a context of pure metabolic acidosis (PaCO2 < 35 mmHg) or in a context of mixed acidosis with a PaCO2 ≥ 50 mmHg without possibility of increasing alveolar ventilation, acute pulmonary edema due to fluid overload despite diuretic therapy leading to severe hypoxemia requiring oxygen flow rate >5 l/min to maintain SpO2 > 95% or FiO2 > 50% under invasive or noninvasive mechanical ventilation. The primary outcome measure is overall survival, measured from randomization (D0) until death, regardless of the cause. The minimum follow-up duration for each patient will be 60 days. Two interim analyses are planned, blinded to group allocation. It is expected that there will be 620 subjects in all. DISCUSSION: The AKIKI study will be one of the very few large randomized controlled trials evaluating mortality according to the timing of RRT in critically ill patients with AKI classification stage 3 (KDIGO 2012). Results should help clinicians decide when to initiate RRT. TRIAL REGISTRATION: ClinicalTrials.gov NCT01932190.

Impact of early enteral versus parenteral nutrition on mortality in patients requiring mechanical ventilation and catecholamines: study protocol for a randomized controlled trial (NUTRIREA-2).

BACKGROUND: Nutritional support is crucial to the management of patients receiving invasive mechanical ventilation (IMV) and the most commonly prescribed treatment in intensive care units (ICUs). International guidelines consistently indicate that enteral nutrition (EN) should be preferred over parenteral nutrition (PN) whenever possible and started as early as possible. However, no adequately designed study has evaluated whether a specific nutritional modality is associated with decreased mortality. The primary goal of this trial is to assess the hypothesis that early first-line EN, as compared to early first-line PN, decreases day 28 all-cause mortality in patients receiving IMV and vasoactive drugs for shock. METHODS/DESIGN: The NUTRIREA-2 study is a multicenter, open-label, parallel-group, randomized controlled trial comparing early PN versus early EN in critically ill patients requiring IMV for an expected duration of at least 48 hours, combined with vasoactive drugs, for shock. Patients will be allocated at random to first-line PN for at least 72 hours or to first-line EN. In both groups, nutritional support will be started within 24 hours after IMV initiation. Calorie targets will be 20 to 25 kcal/kg/day during the first week, then 25 to 30 kcal/kg/day thereafter. Patients receiving PN may be switched to EN after at least 72 hours in the event of shock resolution (no vasoactive drugs for 24 consecutive hours and arterial lactic acid level below 2 mmol/L). On day 7, all patients receiving PN and having no contraindications to EN will be switched to EN. In both groups, supplemental PN may be added to EN after day 7 in patients with persistent intolerance to EN and inadequate calorie intake. We plan to recruit 2,854 patients at 44 participating ICUs. DISCUSSION: The NUTRIREA-2 study is the first large randomized controlled trial designed to assess the hypothesis that early EN improves survival compared to early PN in ICU patients. Enrollment started on 22 March 2013 and is expected to end in November 2015. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01802099 (registered 27 February 2013).

Induced hypothermia in severe bacterial meningitis: a randomized clinical trial.

IMPORTANCE: Despite advances in care, mortality and morbidity remain high in adults with acute bacterial meningitis, particularly when due to Streptococcus pneumoniae. Induced hypothermia is beneficial in other conditions with global cerebral hypoxia. OBJECTIVE: To test the hypothesis that induced hypothermia improves outcome in patients with severe bacterial meningitis. DESIGN, SETTING, AND PATIENTS: An open-label, multicenter, randomized clinical trial in 49 intensive care units in France, February 2009-November 2011. In total, 130 patients were assessed for eligibility and 98 comatose adults (Glasgow Coma Scale [GCS] score of ≤8 for <12 hours) with community-acquired bacterial meningitis were randomized. INTERVENTIONS: Hypothermia group received a loading dose of 4°C cold saline and were cooled to 32°C to 34°C for 48 hours. The rewarming phase was passive. Controls received standard care. MAIN OUTCOMES AND MEASURES: Primary outcome measure was the Glasgow Outcome Scale score at 3 months (a score of 5 [favorable outcome] vs a score of 1-4 [unfavorable outcome]). All patients received appropriate antimicrobial therapy and vital support. Analyses were performed on an intention-to-treat basis. The data and safety monitoring board (DSMB) reviewed severe adverse events and mortality rate every 50 enrolled patients. RESULTS: After inclusion of 98 comatose patients, the trial was stopped early at the request of the DSMB because of concerns over excess mortality in the hypothermia group (25 of 49 patients [51%]) vs the control group (15 of 49 patients [31%]; relative risk [RR], 1.99; 95% CI, 1.05-3.77; P = .04). Pneumococcal meningitis was diagnosed in 77% of patients. Mean (SD) temperatures achieved 24 hours after randomization were 33.3°C (0.9°C) and 37.0°C (0.9°C) in the hypothermia and control group, respectively. At 3 months, 86% in the hypothermia group compared with 74% of controls had an unfavorable outcome (RR, 2.17; 95% CI, 0.78-6.01; P = .13). After adjustment for age, score on GCS at inclusion, and the presence of septic shock at inclusion, mortality remained higher, although not significantly, in the hypothermia group (hazard ratio, 1.76; 95% CI, 0.89-3.45; P = .10). Subgroup analysis on patients with pneumococcal meningitis showed similar results. Post hoc analysis showed a low probability to reach statistically significant difference in favor of hypothermia at the end of the 3 planned sequential analyses (probability to conclude in favor of futility, 0.977). CONCLUSIONS AND RELEVANCE: Moderate hypothermia did not improve outcome in patients with severe bacterial meningitis and may even be harmful. Careful evaluation of safety issues in future trials on hypothermia are needed and may have important implications in patients presenting with septic shock or stroke. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00774631.

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.).

Growth-arrest-specific 6 (GAS6) protein in ARDS patients: determination of plasma levels and influence of PEEP setting.

BACKGROUND: Growth-arrest-specific protein 6 (GAS6) is a vitamin K-dependent protein expressed by endothelial cells and leukocytes participating in cell survival, migration and proliferation and involved in many pathological situations. The aim of our study was to assess its implication in ARDS and its variation according to PEEP setting, considering that different cyclic stresses could alter GAS6 plasma levels. METHODS: Our subjects were enrolled in the ExPress study comparing a minimal alveolar distention (low-PEEP) ventilatory strategy to a maximal alveolar recruitment (high-PEEP) strategy in ARDS. Plasma GAS6, interleukin-8 (IL-8), and vascular endothelial growth factor (VEGF) levels were measured at day 0 and day 3 by enzyme-linked immunosorbent assay in blood samples prospectively collected during the study for a subset of 52 subjects included in 8 centers during year 2005. RESULTS: We found that GAS6 plasma level was elevated in the whole population at day 0: median 106 ng/mL IQR 77-139 ng/mL, with significant correlations with IL-8, the Simplified Acute Physiology Score II and the Organ Dysfunction and Infection scores. Statistically significant decreases in GAS6 and IL-8 plasma levels were observed between day 0 and day 3 in the high-PEEP group (P = .02); while there were no differences between day 0 and day 3 in the low-PEEP group. CONCLUSIONS: GAS6 plasma level is elevated in ARDS patients. The high-PEEP strategy is associated with a decrease in GAS6 and IL-8 plasma levels at day 3, without significant differences in day 28 mortality between the 2 groups. (Clinicaltrials.gov NCT00188058).

Noninvasive ventilation and weaning in patients with chronic hypercapnic respiratory failure: a randomized multicenter trial.

RATIONALE: The use of noninvasive ventilation (NIV) as an early weaning/extubation technique from mechanical ventilation remains controversial. OBJECTIVES: To investigate NIV effectiveness as an early weaning/extubation technique in difficult-to-wean patients with chronic hypercapnic respiratory failure (CHRF). METHODS: In 13 intensive care units, 208 patients with CHRF intubated for acute respiratory failure (ARF) who failed a first spontaneous breathing trial were randomly assigned to three groups: conventional invasive weaning group (n = 69), extubation followed by standard oxygen therapy (n = 70), or NIV (n = 69). NIV was permitted as rescue therapy for both non-NIV groups if postextubation ARF occurred. Primary endpoint was reintubation within 7 days after extubation. Secondary endpoints were: occurrence of postextubation ARF or death within 7 days after extubation, use of rescue postextubation NIV, weaning time, and patient outcomes. MEASUREMENTS AND MAIN RESULTS: Reintubation rates were 30, 37, and 32% for invasive weaning, oxygen-therapy, and NIV groups, respectively (P = 0.654). Weaning failure rates, including postextubation ARF, were 54, 71, and 33%, respectively (P < 0.001). Rescue NIV success rates for invasive and oxygen-therapy groups were 45 and 58%, respectively (P = 0.386). By design, intubation duration was 1.5 days longer for the invasive group than in the two others. Apart from a longer weaning time in NIV than in invasive group (2.5 vs. 1.5 d; P = 0.033), no significant outcome difference was observed between groups. CONCLUSIONS: No difference was found in the reintubation rate between the three weaning strategies. NIV decreases the intubation duration and may improve the weaning results in difficult-to-wean patients with CHRF by reducing the risk of postextubation ARF. The benefit of rescue NIV in these patients deserves confirmation.

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.

Effects of contrast material on computed tomographic measurements of lung volumes in patients with acute lung injury.

BACKGROUND: Intravenous injection of contrast material is routinely performed in order to differentiate nonaerated lung parenchyma from pleural effusion in critically ill patients undergoing thoracic computed tomography (CT). The aim of the present study was to evaluate the effects of contrast material on CT measurement of lung volumes in 14 patients with acute lung injury. METHOD: A spiral thoracic CT scan, consisting of contiguous axial sections of 10 mm thickness, was performed from the apex to the diaphragm at end-expiration both before and 30 s (group 1; n = 7) or 15 min (group 2; n = 7) after injection of 80 ml contrast material. Volumes of gas and tissue, and volumic distribution of CT attenuations were measured before and after injection using specially designed software (Lungview; Institut National des Télécommunications, Evry, France). The maximal artifactual increase in lung tissue resulting from a hypothetical leakage within the lung of the 80 ml contrast material was calculated. RESULTS: Injection of contrast material significantly increased the apparent volume of lung tissue by 83 +/- 57 ml in group 1 and 102 +/- 80 ml in group 2, whereas the corresponding maximal artifactual increases in lung tissue were 42 +/- 52 ml and 31 +/- 18 ml. CONCLUSION: Because systematic injection of contrast material increases the amount of extravascular lung water in patients with acute lung injury, it seems prudent to avoid this procedure in critically ill patients undergoing a thoracic CT scan and to reserve its use for specific indications.

Significado do ponto de inflexäo inferior da curva pressão-volume em pacientes com insuficiência respiratória aguda: avaliaçäo por tomografia computadorizada / Significance of lower inflection point detected on lung pressure-volume: an assessment by computed tomography

O objetivo deste estudo foi avaliar, através de tomografia computadorizada, a morfologia pulmonar em pacientes com lesão pulmonar aguda, de acordo com a presença ou ausência de ponto de inflexão inferior (Pinf) nas curvas pressão-volume e comparar os efeitos da pressão expiratória final positiva (PEEP)...

Lavagem expiratória verus otimização da ventilação mecência convencional durantehipercapnia permissiva em pacientes com insuficiência respiratória aguda / Expiratory washout versus optimization of mechanical ventilation during permissive hypercapnia in patients with severe acute respiratory distress syndrome

O objetivo deste estudo foi comparar três técnicas ventilatórias para reduzir pressão arterial de CO2 em pacientes com insuficiência respiratória aguda severa e em hipercapnia permissiva...

Avaliaçäo por tomografia computadorizada da hiperdistensão pulmonar induzida por PEEP em indivíduos normais e em pacientes com insuficiência respiratória aguda / Computed tomography assessment of positive end-expiratory pressure-induced lung overdistension

O objetivo do presente estudo foi determinar o limite tomográfico da hiperdistensão pulmonar em indivíduos normais, bem como avaliar o recrutamento e a hiperdistensão pulmonares induzidos pela pressão expiratória final positiva em pacientes com lesão pulmonar aguda...

Comparaçäo de três métodos para medida das curvas de complacência em pacientes com insuficiência respiratória aguda / Comparison of three methods for measuring pressure-volume curves in patients with acute respiratory failure

As medidas da complacência respiratória a partir das curvas pressão-volume são indicadas para avaliar a gravidade da insuficiência respiratória aguda. O objetivo do presente estudo foi comparar diferentes métodos de obtenção das curvas pressão-volume e avaliar sua reprodutibilidade e fidedignidade...