Spontaneous breathing trial with pressure support on positive end-expiratory pressure and extensive use of non-invasive ventilation versus T-piece in difficult-to-wean patients from mechanical ventilation: a randomized controlled trial.

BACKGROUND: The aim of this study is to assess whether a strategy combining spontaneous breathing trial (SBT) with both pressure support (PS) and positive end-expiratory pressure (PEEP) and extended use of post-extubation non-invasive ventilation (NIV) (extensively-assisted weaning) would shorten the time until successful extubation as compared with SBT with T-piece (TP) and post-extubation NIV performed in selected patients as advocated by guidelines (standard weaning), in difficult-to-wean patients from mechanical ventilation. METHODS: The study is a single-center prospective open label, randomized controlled superiority trial with two parallel groups and balanced randomization with a 1:1 ratio. Eligible patients were intubated patients mechanically ventilated for more than 24 h who failed their first SBT using TP. In the extensively-assisted weaning group, SBT was performed with PS (7 cmH2O) and PEEP (5 cmH2O). In case of SBT success, an additional SBT with TP was performed. Failure of this SBT-TP was an additional criterion for post-extubation NIV in this group in addition to other recommended criteria. In the standard weaning group, SBT was performed with TP, and NIV was performed according to international guidelines. The primary outcome criterion was the time between inclusion and successful extubation evaluated with a Cox model with adjustment on randomization strata. RESULTS: From May 2019 to March 2023, 98 patients were included and randomized in the study (49 in each group). Four patients were excluded from the intention-to-treat population (2 in both groups); therefore, 47 patients were analyzed in each group. The extensively-assisted weaning group had a higher median age (68 [58-73] vs. 62 [55-71] yrs.) and similar sex ratio (62% male vs. 57%). Time until successful extubation was not significantly different between extensively-assisted and standard weaning groups (median, 172 [50-436] vs. 95 [47-232] hours, Cox hazard ratio for successful extubation, 0.88 [95% confidence interval: 0.55-1.42] using the standard weaning group as a reference; p = 0.60). All secondary outcomes were not significantly different between groups. CONCLUSION: An extensively-assisted weaning strategy did not lead to a shorter time to successful extubation than a standard weaning strategy. Trial registration The trial was registered on ClinicalTrials.gov (NCT03861117), on March 1, 2019, before the inclusion of the first patient. https://clinicaltrials.gov/study/NCT03861117 .

Ultra-low tidal volume ventilation for COVID-19-related ARDS in France (VT4COVID): a multicentre, open-label, parallel-group, randomised trial.

BACKGROUND: COVID-19-related acute respiratory distress syndrome (ARDS) is associated with a high mortality rate and longer mechanical ventilation. We aimed to assess the effectiveness of ventilation with ultra-low tidal volume (ULTV) compared with low tidal volume (LTV) in patients with COVID-19-related ARDS. METHODS: This study was a multicentre, open-label, parallel-group, randomised trial conducted in ten intensive care units in France. Eligible participants were aged 18 years or older, received invasive mechanical ventilation for COVID-19 (confirmed by RT-PCR), had ARDS according to the Berlin definition, a partial pressure of arterial oxygen to inspiratory oxygen fraction (PaO2/FiO2) ratio of 150 mm Hg or less, a tidal volume (VT) of 6·0 mL/kg predicted bodyweight or less, and received continuous intravenous sedation. Patients were randomly assigned (1:1) using randomisation blocks to receive ULTV (intervention group) aiming for VT of 4·0 mL/kg predicted bodyweight or LTV (control group) aiming for VT 6·0 mL/kg predicted bodyweight. Participants, investigators, and outcome assessors were not masked to group assignment. The primary outcome was a ranked composite score based on all-cause mortality at day 90 as the first criterion and ventilator-free days among patients alive at day 60 as the second criterion. Effect size was computed with the unmatched win ratio, on the basis of pairwise prioritised comparison of primary outcome components between every patient in the ULTV group and every patient in the LTV group. The unmatched win ratio was calculated as the ratio of the number of pairs with more favourable outcome in the ULTV group over the number of pairs with less favourable outcome in the ULTV group. Primary analysis was done in the modified intention-to-treat population, which included all participants who were randomly assigned and not lost to follow-up. This trial is registered with ClinicalTrials.gov, NCT04349618. FINDINGS: Between April 15, 2020, and April 13, 2021, 220 patients were included and five (2%) were excluded. 215 patients were randomly assigned (106 [49%] to the ULTV group and 109 [51%] to the LTV group). 58 (27%) patients were female and 157 (73%) were male. The median age was 68 years (IQR 60-74). 214 patients completed follow-up (one lost to follow-up in the ULTV group) and were included in the modified intention-to-treat analysis. The primary outcome was not significantly different between groups (unmatched win ratio in the ULTV group 0·85 [95% CI 0·60 to 1·19]; p=0·38). 46 (44%) of 105 patients in the ULTV group and 43 (39%) of 109 in the LTV group died by day 90 (absolute difference 4% [-9 to 18]; p=0·52). The rate of severe respiratory acidosis in the first 28 days was higher in the ULTV group than in the LTV group (35 [33%] vs 14 [13%]; absolute difference 20% [95% CI 9 to 31]; p=0·0004). INTERPRETATION: In patients with moderate-to-severe COVID-19-related ARDS, there was no significant difference with ULTV compared with LTV in the composite score based on mortality and ventilator-free days among patients alive at day 60. These findings do not support the systematic use of ULTV in patients with COVID-19-related ARDS. FUNDING: French Ministry of Solidarity and Health and Hospices Civils de Lyon.

Nurse-to-Nurse Familiarity and Mortality in the Critically Ill: A Multicenter Observational Study.

Rationale: Nurse-to-nurse familiarity at work should strengthen the components of teamwork and enhance its efficiency. However, its impact on patient outcomes in critical care remains poorly investigated. Objectives: To explore the role of nurse-to-nurse familiarity on inpatient deaths during ICU stay. Methods: This was a retrospective observational study in eight adult academic ICUs between January 1, 2011 and December 31, 2016. Measurements and Main Results: Nurse-to-nurse familiarity was measured across day and night 12-hour daily shifts as the mean number of previous collaborations between each nursing team member during previous shifts within the given ICU (suboptimal if <50). Primary outcome was a shift with at least one inpatient death, excluding death of patients with a decision to forego life-sustaining therapy. A multiple modified Poisson regression was computed to identify the determinants of mortality per shift, taking into account ICU, patient characteristics, patient-to-nurse and patient-to-assistant nurse ratios, nurse experience length, and workload. A total of 43,479 patients were admitted, of whom 3,311 (8%) died. The adjusted model showed a lower risk of a shift with mortality when nurse-to-nurse familiarity increased in the shift (relative risk, 0.90; 95% confidence interval per 10 shifts, 0.82-0.98; P = 0.012). Low nurse-to-nurse familiarity during the shift combined with suboptimal patient-to-nurse and patient-to-assistant nurse ratios (suboptimal if >2.5 and >4, respectively) were associated with increased risk of shift with mortality (relative risk, 1.84; 95% confidence interval, 1.15-2.96; P < 0.001). Conclusions: Shifts with low nurse-to-nurse familiarity were associated with an increased risk of patient deaths.

Causes of acute respiratory failure in patients with small-vessel vasculitis admitted to intensive care units: a multicenter retrospective study.

RATIONALE: Acute respiratory failure (ARF) in patients admitted to the intensive care unit (ICU) with known or de novo small-vessel vasculitis (Svv) may be secondary to the underlying immune disease or to other causes. Early identification of the cause of ARF is essential to initiate the most appropriate treatment in a timely fashion. METHODS: A retrospective multicenter study in 10 French ICUs from January 2007 to January 2018 to assess the clinical presentation, main causes and outcome of ARF associated with Svv, and to identify variables associated with non-immune etiology of ARF in patients with known Svv. RESULTS: During the study period, 121 patients [62 (50-75) years; 62% male; median SAPSII and SOFA scores 39 (27-52) and 6 (4-8), respectively] were analyzed. An immune cause was identified in 67 (55%), and a non-immune cause in 54 (45%) patients. ARF was associated with several causes in 43% (n = 52) of cases. The main immune cause was diffuse alveolar hemorrhage (DAH) (n = 47, 39%), whereas the main non-immune cause was pulmonary infection (n = 35, 29%). The crude 90-day and 1-year mortality were higher in patients with non-immune ARF, as compared with their counterparts (32% and 38% vs. 15% and 20%, respectively; both p = 0.03), but was marginally significantly higher after adjusted analysis in a Cox model (p = 0.053). Among patients with a known Svv (n = 70), immunosuppression [OR 9.41 (1.52-58.3); p = 0.016], and a low vasculitis activity score [0.84 (0.77-0.93)] were independently associated with a non-immune cause, after adjustment for the time from disease onset to ARF, time from respiratory symptoms to ICU admission, and severe renal failure. CONCLUSIONS: An extensive diagnosis workup is mandatory in ARF revealing or complicating Svv. Non-immune causes are involved in 43% of cases, and their short and mid-term prognosis may be poorer than those of immune ARF. Readily identified predictive factors of a non-immune cause could help avoiding unnecessary immunosuppressive therapies.

Lung and chest wall mechanics in patients with acute respiratory distress syndrome, expiratory flow limitation, and airway closure.

Tidal expiratory flow limitation (EFL), which may herald airway closure (AC), is a mechanism of loss of aeration in ARDS. In this prospective, short-term, two-center study, we measured static and dynamic chest wall (Est,cw and Edyn,cw) and lung (Est,L and Edyn,L) elastance with esophageal pressure, EFL, and AC at 5 cmH2O positive end-expiratory pressure (PEEP) in intubated, sedated, and paralyzed ARDS patients. For EFL determination, we used the atmospheric method and a new device allowing comparison of tidal flow during expiration to PEEP and to atmosphere. AC was validated when airway opening pressure (AOP) assessed from volume-pressure curve was found greater than PEEP by at least 1 cmH2O. EFL was defined whenever flow did not increase between exhalation to PEEP and to atmosphere over all or part of expiration. Elastance values were expressed as percentage of normal predicted values (%N). Among the 25 patients included, eight had EFL (32%) and 13 AOP (52%). Between patients with and without EFL Edyn,cw [median (1st to 3rd quartiles)] was 70 (16-127) and 102 (70-142) %N (P = 0.32) and Edyn,L338 (332-763) and 224 (160-275) %N (P < 0.001). The corresponding values for Est,cw and Est,L were 70 (56-88) and 85 (64-103) %N (P = 0.35) and 248 (206-348) and 170 (144-195) (P = 0.02), respectively. Dynamic EL had an area receiver operating characteristic curve of 0.88 [95% confidence intervals 0.83-0.92] for EFL and 0.74[0.68-0.79] for AOP. Higher Edyn,L was accurate to predict EFL in ARDS patients; AC can occur independently of EFL, and both should be assessed concurrently in ARDS patients.NEW & NOTEWORTHY Expiratory flow limitation (EFL) and airway closure (AC) were observed in 32% and 52%, respectively, of 25 patients with ARDS investigated during mechanical ventilation in supine position with a positive end-expiratory pressure of 5 cmH2O. The performance of dynamic lung elastance to detect expiratory flow limitation was good and better than that to detect airway closure. The vast majority of patients with EFL also had AC; however, AC can occur in the absence of EFL.

Low-pressure support vs automatic tube compensation during spontaneous breathing trial for weaning.

BACKGROUND: During spontaneous breathing trial, low-pressure support is thought to compensate for endotracheal tube resistance, but it actually should provide overassistance. Automatic tube compensation is an option available in the ventilator to compensate for flow-resistance of endotracheal tube. Its effects on patient effort have been poorly investigated. We aimed to compare the effects of low-pressure support and automatic tube compensation during spontaneous breathing trial on breathing power and lung ventilation distribution. RESULTS: We performed a randomized crossover study in 20 patients ready to wean. Each patient received both methods for 30 min separated by baseline ventilation: pressure support 0 cmH2O and automatic tube compensation 100% in one period and pressure support 7 cmH2O without automatic tube compensation in the other period, a 4 cmH2O positive end-expiratory pressure being applied in each. Same ventilator brand (Evita XL, Draeger, Germany) was used. Breathing power was assessed from Campbell diagram with esophageal pressure, airway pressure, flow and volume recorded by a data logger. Lung ventilation distribution was assessed by using electrical impedance tomography (Pulmovista, Draeger, Germany). During the last 2 min of low-pressure support and automatic compensation period breathing power and lung ventilation distribution were measured on each breath. Breathing power generated by the patient's respiratory muscles was 7.2 (4.4-9.6) and 9.7 (5.7-21.9) J/min in low-pressure support and automatic tube compensation periods, respectively (P = 0.011). Lung ventilation distribution was not different between the two methods. CONCLUSIONS: We found that ATC was associated with higher breathing power than low PS during SBT without altering the distribution of lung ventilation.

Effects of positive end-expiratory pressure strategy in supine and prone position on lung and chest wall mechanics in acute respiratory distress syndrome.

BACKGROUND: In acute respiratory distress syndrome (ARDS) patients, it has recently been proposed to set positive end-expiratory pressure (PEEP) by targeting end-expiratory transpulmonary pressure. This approach, which relies on the measurement of absolute esophageal pressure (Pes), has been used in supine position (SP) and has not been investigated in prone position (PP). Our purposes were to assess Pes-guided strategy to set PEEP in SP and in PP as compared with a PEEP/FIO2 table and to explore the early (1 h) and late (16 h) effects of PP on lung and chest wall mechanics. RESULTS: We performed a prospective, physiologic study in two ICUs in university hospitals on ARDS patients with PaO2/FIO2 < 150 mmHg. End-expiratory Pes (Pes,ee) was measured in static (zero flow) condition. Patients received PEEP set according to a PEEP/FIO2 table then according to the Pes-guided strategy targeting a positive (3 ± 2 cmH2O) static end-expiratory transpulmonary pressure in SP. Then, patients were turned to PP and received same amount of PEEP from PEEP/FIO2 table then Pes-guided strategy. Respiratory mechanics, oxygenation and end-expiratory lung volume (EELV) were measured after 1 h of each PEEP in each position. For the rest of the 16-h PP session, patients were randomly allocated to either PEEP strategy with measurements done at the end. Thirty-eight ARDS patients (27 male), mean ± SD age 63 ± 13 years, were included. There were 33 primary ARDS and 26 moderate ARDS. PaO2/FIO2 ratio was 120 ± 23 mmHg. At same PEEP/FIO2 table-related PEEP, Pes,ee averaged 9 ± 4 cmH2O in both SP and PP (P = 0.88). With PEEP/FIO2 table and Pes-guided strategy, PEEP was 10 ± 2 versus 12 ± 4 cmH2O in SP and 10 ± 2 versus 12 ± 5 cmH2O in PP (PEEP strategy effect P = 0.05, position effect P = 0.96, interaction P = 0.96). With the Pes-guided strategy, chest wall elastance increased regardless of position. Lung elastance and transpulmonary driving pressure decreased in PP, with no effect of PEEP strategy. Both PP and Pes-guided strategy improved oxygenation without interaction. EELV did not change with PEEP strategy. At the end of PP session, respiratory mechanics did not vary but EELV and PaO2/FIO2 increased while PaCO2 decreased. CONCLUSIONS: There was no impact of PP on Pes measurements. PP had an immediate improvement effect on lung mechanics and a late lung recruitment effect independent of PEEP strategy.

Reliability of Tidal Volume in Average Volume Assured Pressure Support Mode.

BACKGROUND: Remote monitoring is increasingly used in patients who receive home mechanical ventilation. The average volume assured pressure support mode is a target volume pressure preset mode that delivers a given tidal volume (VT) within a range of controlled inspiratory pressures. In a mode such as this, it is important to verify that the VT value retrieved from the ventilator SD card is accurate. METHODS: A lung model was set with C (Compliance) 0.075 L/cm H2O and RI (Inspiratory resistance)-RE (Expiratory resistance) 15-25 cm H2O/L/s (model 1) or with C 0.050 L/cm H2O and RI 6 cm H2O/L/s (model 2) and 6 cm H2O effort. Three home-care ventilators (A40, PrismaST30, and Vivo40) were set to average volume assured pressure support mode with 0.3 and 0.6 L VT each at PEEP 5 and 10 cm H2O, and were connected to the lung model with and without nonintentional leak. The reference airway pressure and flow were measured by a data logger. VT was expressed in body temperature and pressure saturated. We assessed the difference in VT between the ventilator SD card and a data logger relative to set VT and factors associated with its magnitude. RESULTS: For A40, PrismaST30, and Vivo40, the adjusted mean VT differences between the ventilator SD card and the data logger were -0.053 L (95% CI -0.067 to -0.039 L) (P < .001), -0.002 L (95%CI -0.022 to 0.019 L) (P = .86), and -0.067 L (95% CI -0.007 to 0.127 L) (P = .03), respectively. The partial Spearman correlation coefficients between the ventilator SD card and a data logger were 0.89 (P < .001), 0.59 (P < .001), and 0.78 (P < .001), respectively to the ventilators. The relative variations in measured VT from the set VT were 16.0, -12.0, and 6.7% for the ventilator SD card, and were -2.5, -7.5, and -27.2% for the data logger, respectively. The discrepancy in ventilator between SD card and data logger were influenced by PEEP for the PrismaST30 ventilator, nonintentional leak for the Vivo40 ventilator and PEEP, nonintentional leak, and underlying disease, the effect of each depending on the levels of the other factors, for the A40 ventilator. CONCLUSIONS: In the 3 home-care ventilators, the ventilator SD card underestimated VT. Factors involved in this difference differed among the ventilators.

Accuracy of Delivery and Effects on Absolute Humidity of Low Tidal Volume by ICU Ventilators.

BACKGROUND: During extracorporeal membrane oxygenation for ARDS, a range of 1-4 mL/kg predicted body weight tidal volume (VT) is commonly used. We explored whether such a low VT could be adequately delivered by ICU ventilators, and whether such low VTs prevent the heated humidifier (HH) from reaching the recommended target of 33 mg/L absolute humidity (AH). METHODS: We attached a lung model to 5 ICU ventilators set in volume controlled mode and body temperature and pressure saturated. We ran 2 protocols over a 100-280 mL VT range used with adult or neonatal breathing circuit at a breathing frequency (f) of 15 (f15) or 30 (f30) breaths/min. In the first protocol, with the HH off, VT was measured with a dedicated data logger and expressed in body temperature and pressure saturated. The relationships of measured VT to set VT were studied, and the relative error in VT was analyzed within its 10% boundaries. In the second protocol, the HH was on, and we measured AH using a psychrometric method. The relationship of AH to set VT was analyzed with linear regression. RESULTS: For the 5 ventilators used, the slope (95% CI) between measured VT versus set VT averaged 0.93 (0.92-0.93), 0.93 (0.93-0.94), 0.91 (0.90-0.91), and 0.91 (0.90-0.91) mL/mL for adult and neonatal circuits at f15 and f30, respectively (P < .05 vs 1 in each instance), indicating a systematic under-delivery of VT. The VT relative error fell within the ±10% accuracy range for only 2 ventilators with adult circuits at f15 and f30. AH increased linearly with VT. The recommended target of 33 mg/L AH was reached with all of the ventilators for the adult circuit at f30 only. The minimum volume that met the recommended threshold for AH was 100, 150, 190, 160, and 100 mL for the G5, Carestation, PB980, Servo-U, and V500 ventilators, respectively, at f30. CONCLUSION: Low VT was systematically under-delivered by modern ICU ventilators by roughly 7-9%. To meet the recommended target of 33 mg/L AH, adult circuit at f30 should be used.

Variability of Tidal Volume in Patient-Triggered Mechanical Ventilation in ARDS.

BACKGROUND: Limiting tidal volume (VT) in patients with ARDS may not be achieved once patient-triggered breaths occur. Furthermore, ICU ventilators offer numerous patient-triggered modes that work differently across brands. We systematically investigated, using a bench model, the effect of patient-triggered modes on the size and variability of VT at different breathing frequencies (f), patient effort, and ARDS severity. METHODS: We used a V500 Infinity ICU ventilator connected to an ASL 5000 lung model whose compliance was mimicking mild, moderate, and severe ARDS. Thirteen patient-triggered modes were tested, falling into 3 categories, namely volume control ventilation with mandatory minute ventilation; pressure control ventilation, including airway pressure release ventilation (APRV); and pressure support ventilation. Two levels of f and effort were tested for each ARDS severity in each mode. Median (first-third quartiles) VT was compared across modes using non-parametric tests. The probability of VT > 6 mL/kg ideal body weight was assessed by binomial regression and expressed as the odds ratio (OR) with 95% CI. VT variability was measured from the coefficient of variation. RESULTS: VT distribution over all f, effort, and ARDS categories significantly differed across modes (P < .001, Kruskal-Wallis test). VT was significantly greater with pressure support (OR 420 mL, 95% CI 332-527 mL) than with any other mode except for variable pressure support level. Risk for VT to be > 6 mL/kg was significantly increased with spontaneous breaths patient-triggered by pressure support (OR 19.36, 95% CI 12.37-30.65) and significantly reduced in APRV (OR 0.44, 95% CI 0.26-0.72) and pressure support with guaranteed volume mode. The risk increased with increasing effort and decreasing f. Coefficient of variation of VT was greater for low f and volume control-mandatory minute ventilation and pressure control modes. APRV had the greatest within-mode variability. CONCLUSIONS: Risk of VT > 6 mL/kg was significantly reduced in APRV and pressure support with guaranteed volume mode. APRV had the highest variability. Pressure support with guaranteed volume could be tested in patients with ARDS.

A bench evaluation of fraction of oxygen in air delivery and tidal volume accuracy in home care ventilators available for hospital use.

BACKGROUND: Turbine-powered ventilators are not only designed for long-term ventilation at home but also for hospital use. It is important to verify their capabilities in delivering fraction of oxygen in air (FIO2) and tidal volume (VT). METHODS: We assessed the FIO2 accuracy and the VT delivery in four home care ventilators (HCV) on the bench. The four HCV were Astral 150, Elisée 150, Monnal T50 and Trilogy 200 HCV, which were connected to a lung model (ASL 5000). For assessing FIO2 accuracy, lung model was set to mimic an obstructive lung and HCV were set in volume controlled mode (VC). They supplied with air, 3 or 15 L/min oxygen and FIO2 was measured by using a ventilator tester (Citrex H4TM). For the VT accuracy, the lung model was set in a way to mimic three adult configurations (normal, obstructive, or restrictive respiratory disorder) and one pediatric configuration. Each HCV was set in VC. Two VT (300 and 500 mL) in adult lung configuration and one 50 mL VT in pediatric lung configuration, at two positive end expiratory pressures 5 and 10 cmH2O, were tested. VT accuracy was measured as volume error (the relative difference between set and measured VT). Statistical analysis was performed by suing one-factor ANOVA with a Bonferroni correction for multiple tests. RESULTS: For Astral 150, Elisée 150, Monnal T50 and Trilogy 200, FIO2 averaged 99.2%, 93.7%, 86.3%, and 62.1%, respectively, at 15 L/min oxygen supplementation rate (P<0.001). Volume error was 0.5%±0%, -38%±0%, -9%±0%, -29%±0% and -36%±0% for pediatric lung condition (P<0.001). In adult lung configurations, Monnal T50 systematically over delivered VT and Trilogy 150 was sensitive to lung configuration when VT was set to 300 mL at either positive end-expiratory pressure (PEEP). CONCLUSIONS: HCV are different in terms of FIO2 efficiency and VT delivery.

Outcomes in critically ill patients with systemic rheumatic disease: a multicenter study.

BACKGROUND: Patients with systemic rheumatic diseases (SRDs) may require ICU management for SRD exacerbation or treatment-related infections or toxicities. METHODS: This was an observational study at 10 university-affiliated ICUs in France. Consecutive patients with SRDs were included. Determinants of ICU mortality were identified through multivariable logistic analysis. RESULTS: Three hundred sixty-three patients (65.3% women; median age, 59 years [interquartile range, 42-70 years]) accounted for 381 admissions. Connective tissue disease (primarily systemic lupus erythematosus) accounted for 66.1% of SRDs and systemic vasculitides for 26.2% (chiefly antineutrophil cytoplasm antibodies-associated vasculitides). SRDs were newly diagnosed in 43 cases (11.3%). Direct admission to the ICU occurred in 143 cases (37.9%). Reasons for ICU admissions were infection (39.9%), SRD exacerbation (34.4%), toxicity (5.8%), or miscellaneous (19.9%). Respiratory involvement was the leading cause of admission (56.8%), followed by shock (41.5%) and acute kidney injury (42.2%). Median Sequential Organ Failure Assessment (SOFA) score on day 1 was 5 (3-8). Mechanical ventilation was required in 57% of cases, vasopressors in 33.9%, and renal replacement therapy in 28.1%. ICU mortality rate was 21.0% (80 deaths). Factors associated with ICU mortality were shock (OR, 3.77; 95% CI, 1.93-7.36), SOFA score at day 1 (OR, 1.19; 95% CI, 1.10-1.30), and direct admission (OR, 0.52; 95% CI, 0.28-0.97). Neither comorbidities nor SRD characteristics were associated with survival. CONCLUSIONS: In patients with SRDs, critical care management is mostly needed only in patients with a previously known SRD; however, diagnosis can be made in the ICU for 12% of patients. Infection and SRD exacerbation account for more than two-thirds of these situations, both targeting chiefly the lungs. Direct admission to the ICU may improve outcomes.

An experimental model to investigate the targeting accuracy of MR-guided focused ultrasound ablation in liver.

BACKGROUND: Magnetic Resonance-guided High Intensity Focused Ultrasound (MRgHIFU) is a hybrid technology that aims to offer non-invasive thermal ablation of targeted tumors or other pathological tissues. Acoustic aberrations and non-linear wave propagating effects may shift the focal point significantly away from the prescribed (or, theoretical) position. It is therefore mandatory to evaluate the spatial accuracy of ablation for a given HIFU protocol and/or device. We describe here a method for producing a user-defined ballistic target as an absolute reference marker for MRgHIFU ablations. METHODS: The investigated method is based on trapping a mixture of MR contrast agent and histology stain using radiofrequency (RF) ablation causing cell death and coagulation. A dedicated RF-electrode was used for the marker fixation as follows: a RF coagulation (4 W, 15 seconds) and injection of the mixture followed by a second RF coagulation. As a result, the contrast agent/stain is encapsulated in the intercellular space. Ultrasonography imaging was performed during the procedure, while high resolution T1w 3D VIBE MR acquisition was used right after to identify the position of the ballistic marker and hence the target tissue. For some cases, after the marker fixation procedure, HIFU volumetric ablations were produced by a phased-array HIFU platform. First ex vivo experiments were followed by in vivo investigation on four rabbits in thigh muscle and six pigs in liver, with follow-up at Day 7. RESULTS: At the end of the procedure, no ultrasound indication of the marker's presence could be observed, while it was clearly visible under MR and could be conveniently used to prescribe the HIFU ablation, centered on the so-created target. The marker was identified at Day 7 after treatment, immediately after animal sacrifice, after 3 weeks of post-mortem formalin fixation and during histology analysis. Its size ranged between 2.5 and 4 mm. CONCLUSIONS: Experimental validation of this new ballistic marker method was performed for liver MRgHIFU ablation, free of any side effects (e.g. no edema around the marker, no infection, no bleeding). The study suggests that the absolute reference marker had ultrasound conspicuity below the detection threshold, was irreversible, MR-compatible and MR-detectable, while also being a well-established histology staining technique.

The impact of patient positioning on pressure ulcers in patients with severe ARDS: results from a multicentre randomised controlled trial on prone positioning.

PURPOSE: Placing patients with severe acute respiratory distress syndrome (ARDS) in the prone position has been shown to improve survival as compared to the supine position. However, a higher frequency of pressure ulcers has been reported in patients in the prone position. The objective of this study was to verify the impact of prone positioning on pressure ulcers in patients with severe ARDS. METHODS: This was an ancillary study of a prospective multicentre randomised controlled trial in patients with severe ARDS in which the early application of long prone-positioning sessions was compared to supine positioning in terms of mortality. Pressure ulcers were assessed at the time of randomisation, 7 days later and on discharge from the intensive care unit (ICU), using the four-stage Pressure Ulcers Advisory Panel system. The primary end-point was the incidence (with reference to 1,000 days of invasive mechanical ventilation or 1,000 days of ICU stay) of new patients with pressure ulcers at stage 2 or higher from randomisation to ICU discharge. RESULTS: At randomisation, of the 229 patients allocated to the supine position and the 237 patients allocated to the prone position, the number of patients with pressure ulcers was not significantly different between groups. The incidence of new patients with pressure ulcers from randomisation to ICU discharge was 20.80 and 14.26/1,000 days of invasive mechanical ventilation (P = 0.061) and 13.92 and 7.72/1,000 of ICU days (P = 0.002) in the prone and supine groups, respectively. Position group [odds ratio (OR) 1.5408, P = 0.0653], age >60 years (OR 1.5340, P = 0.0019), female gender (OR 0.5075, P = 0.019), body mass index of >28.4 kg/m(2) (OR 1.9804, P = 0.0037), and a Simplified Acute Physiology Score II at inclusion of >46 (OR 1.2765, P = 0.3158) were the covariates independently associated to the acquisition of pressure ulcers. CONCLUSION: In patients with severe ARDS, prone positioning was associated with a higher frequency of pressure ulcers than the supine position. Prone positioning improves survival in patients with severe ARDS and, therefore, survivors who received this intervention had a greater likelihood of having pressure ulcers documented as part of their follow-up. There are risk groups for the development of pressure ulcers in severe ARDS, and these patients need surveillance and active prevention.

Experimental methods for improved spatial control of thermal lesions in magnetic resonance-guided focused ultrasound ablation.

Magnetic resonance-guided high-intensity focused ultrasound (MRgHIFU, or MRgFUS) is a hybrid technology that was developed to provide efficient and tolerable thermal ablation of targeted tumors or other pathologic tissues, while preserving the normal surrounding structures. Fast 3-D ablation strategies are feasible with the newly available phased-array HIFU transducers. However, unlike fixed heating sources for interstitial ablation (radiofrequency electrode, microwave applicator, infra-red laser applicator), HIFU uses propagating waves. Therefore, the main challenge is to avoid thermo-acoustical adverse effects, such as energy deposition at reflecting interfaces and thermal drift of the focal lesion toward the near field. We report here our investigations on some novel experimental solutions to solve, or at least to alleviate, these generally known tolerability problems in HIFU-based therapy. Online multiplanar MR thermometry was the main investigational tool extensively used in this study to identify the problems and to assess the efficacy of the tested solutions. We present an improved method to cancel the beam reflection at the exit window (i.e., tissue-to-air interface) by creating a multilayer protection, to dissipate the residual HIFU beam by bulk scattering. This study evaluates selective de-activation of transducer elements to reduce the collateral heating at bone surfaces in the far field, mainly during automatically controlled volumetric ablation. We also explore, using hybrid US/MR simultaneous imaging, the feasibility of using disruptive boiling at the focus, both as a far-field self-shielding technique and as an enhanced ablation strategy (i.e., boiling core controlled HIFU ablation).

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.).

Magnetic resonance imaging follow-up of liver growth of neuroendocrine tumors in an experimental mouse model.

Liver metastases in patients with gastroenteropancreatic (GEP) endocrine tumors represent the main factor of adverse prognosis in this tumor type and thus have a strong effect on the therapeutic strategies. Currently, magnetic resonance imaging (MRI) is considered the modality of choice for the noninvasive, in vivo detection of liver metastases. Dedicated MRI protocols suitable for following liver lesion evolution on an experimental model of endocrine tumors could be valuable. An experimental animal model mimicking the clinical situation of intrahepatic dissemination has been designed. The goal of this study was to characterize liver lesions in this athymic nude mouse model and assess the detection sensitivity of MRI using a physiological gating strategy optimized for high magnetic fields. The experiments were performed at 7 T using a dual cardiac-respiratory-triggered multiple spin-echo sequence. This protocol was used to carry out a longitudinal follow-up of hepatic lesions in a group of eight nude mice at different stages: Day 7 (D7), Day 12 (D12), Day 17 (D17) and Day 24 (D24). The hepatic lesion volume fraction (HLVF) was quantified using an adaptive segmentation procedure based on a dual-reference limit. Mean transverse relaxation time T(2) values were quantified from multiple spin-echo images. The first lesions were detected at stage D12 on images with 20-ms TE. From D12, the HLVF increased significantly with stage. The mean T(2) values also increased significantly at D17 and D24. In conclusion, the level of detection and characterization of liver lesions were performed using a devoted protocol with a dedicated high-field MRI synchronization strategy. In future studies, MRI could be used to monitor the effects of targeted therapies on liver endocrine metastases in preclinical animal models.