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1.  Easily identified at-risk patients for extubation failure may benefit from noninvasive ventilation: a prospective before-after study 
Critical Care  2016;20:48.
While studies have suggested that prophylactic noninvasive ventilation (NIV) could prevent post-extubation respiratory failure in the intensive care unit, they appear inconsistent with regard to reintubation. We assessed the impact of a prophylactic NIV protocol on reintubation in a large population of at-risk patients.
Prospective before-after study performed in the medical ICU of a teaching referral hospital. In the control cohort, we determined that patients older than 65 years and those with underlying cardiac or respiratory disease were at high-risk for reintubation. In the interventional cohort, we implemented a protocol using prophylactic NIV in all patients intubated at least 24 h and having one of these risk factors. NIV was immediately applied after planned extubation during at least the first 24 hours. Extubation failure was defined by the need for reintubation within seven days following extubation.
We included 83 patients at high-risk among 132 extubated patients in the control cohort (12-month period) and 150 patients at high-risk among 225 extubated patients in the NIV cohort (18-month period). The reintubation rate was significantly decreased from 28 % in the control cohort (23/83) to 15 % (23/150) in the NIV cohort (p = 0.02 log-rank test), whereas the non-at-risk patients did not significantly differ in the two periods (10.2 % vs. 10.7 %, p = 0.93). After multivariate logistic-regression analysis, the use of prophylactic NIV protocol was independently associated with extubation success.
The implementation of prophylactic NIV after extubation may reduce the reintubation rate in a large population of patients with easily identified risk factors for extubation failure.
PMCID: PMC4770688  PMID: 26926168
2.  Variability is adaptability…also during weaning! 
Critical Care  2014;18(2):127.
Heart rate variability in the frequency domain can now be obtained at the bedside in the ICU. Promising data suggest that it may help to characterize a patient response to a spontaneous breathing trial. Refinement of the analysis could even help to predict the outcome of extubation or at least help to detect early patients at risk of failure. It is possible that combining this type of analysis, the breathing pattern variability, and other objective indices could help clinicians in the decision-making process of weaning and extubation.
PMCID: PMC4057288  PMID: 25029030
3.  Echocardiographic detection of transpulmonary bubble transit during acute respiratory distress syndrome 
Transpulmonary bubble transit (TPBT) detected with contrast echocardiography is reported as a sign of intrapulmonary shunt during cirrhosis or exercise in healthy humans. However, its physiological meaning is not clear during acute respiratory distress syndrome (ARDS). Our aim was to determine the prevalence, significance, and prognosis of TPBT detection during ARDS.
This was a prospective observational study in an academic medical intensive care unit in France. Two hundred and sixteen consecutive patients with moderate-to-severe ARDS underwent transesophageal echocardiography with modified gelatine contrast. Moderate-to-large TPBT was defined as right-to-left passage of at least ten bubbles through a pulmonary vein more than three cardiac cycles after complete opacification of the right atrium. Patients with intra-cardiac shunt through patent foramen ovale were excluded.
The prevalence of moderate-to-large TPBT was 26% (including 42 patients with moderate and 15 with large TPBT). Patients with moderate-to-large TPBT had higher values of cardiac index and heart rate as compared to those without TPBT. There was no significant difference in PaO2/FIO2 ratio between groups, and TPBT was not influenced by end-expiratory positive pressure level in 93% of tested patients. Prevalence of septic shock was higher in the group with moderate-to-large TPBT. Patients with moderate-to-large TPBT had fewer ventilator-free days and intensive care unit-free days within the first 28 days, and higher in-hospital mortality as compared to others.
Moderate-to-large TPBT was detected with contrast echocardiography in 26% of patients with ARDS. This finding was associated with a hyperdynamic and septic state, but did not influence oxygenation.
PMCID: PMC4388070  PMID: 25859416
Echocardiography; Acute respiratory distress syndrome; Shunt
4.  Sleep continuity: a new metric to quantify disrupted hypnograms in non-sedated intensive care unit patients 
Critical Care  2014;18(6):628.
Sleep in intensive care unit (ICU) patients is severely altered. In a large proportion of critically ill patients, conventional sleep electroencephalogram (EEG) patterns are replaced by atypical sleep. On the other hand, some non-sedated patients can display usual sleep EEG patterns. In the latter, sleep is highly fragmented and disrupted and conventional rules may not be optimal. We sought to determine whether sleep continuity could be a useful metric to quantify the amount of sleep with recuperative function in critically ill patients with usual sleep EEG features.
We retrospectively reanalyzed polysomnographies recorded in non-sedated critically ill patients requiring non-invasive ventilation (NIV) for acute hypercapnic respiratory failure. Using conventional rules, we built two-state hypnograms (sleep and wake) and identified all sleep episodes. The percentage of time spent in sleep bouts (<10 minutes), short naps (>10 and <30 minutes) and long naps (>30 minutes) was used to describe sleep continuity. In a first study, we compared these measures regarding good (NIV success) or poor outcome (NIV failure). In a second study performed on a different patient group, we compared these measurements during NIV and during spontaneous breathing.
While fragmentation indices were similar in the two groups, the percentage of total sleep time spent in short naps was higher and the percentage of sleep time spent in sleep bouts was lower in patients with successful NIV. The percentage of total sleep time spent in long naps was higher and the percentage of sleep time spent in sleep bouts was lower during NIV than during spontaneous breathing; the level of reproducibility of sleep continuity measures between scorers was high.
Sleep continuity measurements could constitute a clinically relevant and reproducible assessment of sleep disruption in non-sedated ICU patients with usual sleep EEG.
Electronic supplementary material
The online version of this article (doi:10.1186/s13054-014-0628-4) contains supplementary material, which is available to authorized users.
PMCID: PMC4271438  PMID: 25420997
6.  Moderately high frequency ventilation with a conventional ventilator allows reduction of tidal volume without increasing mean airway pressure 
The aim of this study was to explore if positive-pressure ventilation delivered by a conventional ICU ventilator at a moderately high frequency (HFPPV) allows a safe reduction of tidal volume (VT) below 6 mL/kg in a porcine model of severe acute respiratory distress syndrome (ARDS) and at a lower mean airway pressure than high-frequency oscillatory ventilation (HFOV).
This is a prospective study. In eight pigs (median weight 34 [29,36] kg), ARDS was induced by pulmonary lavage and injurious ventilation. The animals were ventilated with a randomized sequence of respiratory rates: 30, 60, 90, 120, 150, followed by HFOV at 5 Hz. At each step, VT was adjusted to allow partial pressure of arterial carbon dioxide (PaCO2) to stabilize between 57 and 63 mmHg. Data are shown as median [P25th,P75th].
After lung injury, the PaO2/FiO2 (P/F) ratio was 92 [63,118] mmHg, pulmonary shunt 26 [17,31]%, and static compliance 11 [8,14] mL/cmH2O. Positive end-expiratory pressure (PEEP) was 14 [10,17] cmH2O. At 30 breaths/min, VT was higher than 6 (7.5 [6.8,10.2]) mL/kg, but at all higher frequencies, VT could be reduced and PaCO2 maintained, leading to reductions in plateau pressures and driving pressures. For frequencies of 60 to 150/min, VT progressively fell from 5.2 [5.1,5.9] to 3.8 [3.7,4.2] mL/kg (p < 0.001). There were no detrimental effects in terms of lung mechanics, auto-PEEP generation, hemodynamics, or gas exchange. Mean airway pressure was maintained constant and was increased only during HFOV.
During protective mechanical ventilation, HFPPV delivered by a conventional ventilator in a severe ARDS swine model safely allows further tidal volume reductions. This strategy also allowed decreasing airway pressures while maintaining stable PaCO2 levels.
PMCID: PMC4512987  PMID: 26266914
Mechanical ventilation; Acute lung injury; Critical care unit; Protective ventilation; Acute respiratory distress syndrome; High-frequency ventilation
7.  Safety of performing fiberoptic bronchoscopy in critically ill hypoxemic patients with acute respiratory failure 
Intensive Care Medicine  2012;39(1):45-52.
Safety of fibreoptic bronchoscopy (FOB) in nonintubated critically ill patients with acute respiratory failure have not been extensively evaluated. We aimed to measure the incidence of intubation and need to increase ventilatory support following FOB and to identify predictive factors of this event.
A prospective multicenter observational study was carried out in 8 French adult intensive care units. 169 FOB performed in patients with a PaO2/FiO2 ratio equal or less than 300 were analyzed. Our main end point was intubation rate. The secondary end point was rate of increased ventilatory support defined as greater than a 50% increase in oxygen requirement, the need to start non invasive-positive pressure ventilation (NI-PPV) or increase NI-PPV support.
Within 24 hours, an increase in ventilatory support was required following 59 (35%) bronchoscopies, of which 25 (15%) led to endotracheal intubation. The existence of chronic obstructive pulmonary disease (COPD) (OR:5.2 [1.6–17.8], p=0.007) or immunosuppression (OR : 5.4 [1.7–17.2], p=0.004) were significantly associated with the need for intubation in multivariable analysis. None of the baseline physiological parameters including the PaO2/FiO2 ratio was associated with intubation.
Bronchoscopy is often followed by an increase in ventilatory support in hypoxemic critically ill patients, but less frequently by the need for intubation. COPD, immunosuppression are associated with a need for invasive ventilation in the following 24 hours.
PMCID: PMC3939027  PMID: 23070123
Acute Disease; Adult; Aged; Aged, 80 and over; Anoxia; therapy; Bronchoscopy; Critical Illness; Female; Humans; Male; Middle Aged; Positive-Pressure Respiration; Prospective Studies; Respiration, Artificial; Respiratory Insufficiency; therapy
8.  Feasibility and reliability of an automated controller of inspired oxygen concentration during mechanical ventilation 
Critical Care  2014;18(1):R35.
Hypoxemia and high fractions of inspired oxygen (FiO2) are concerns in critically ill patients. An automated FiO2 controller based on continuous oxygen saturation (SpO2) measurement was tested. Two different SpO2-FiO2 feedback open loops, designed to react differently based on the level of hypoxemia, were compared. The results of the FiO2 controller were also compared with a historical control group.
The system measures SpO2, compares with a target range (92% to 96%), and proposes in real time FiO2 settings to maintain SpO2 within target. In 20 patients under mechanical ventilation, two different FiO2-SpO2 open loops were applied by a dedicated research nurse during 3 hours, each in random order. The times spent in and outside the target SpO2 values were measured. The results of the automatic controller were then compared with a retrospective control group of 30 ICU patients. SpO2-FiO2 values of the control group were collected over three different periods of 6 hours.
Time in the target range was higher than 95% with the controller. When the 20 patients were separated according to the median PaO2/FiO2 (160(133-176) mm Hg versus 239(201-285)), the loop with the highest slope was slightly better (P = 0.047) for the more-hypoxemic patients. Hyperoxemia and hypoxemia durations were significantly shorter with the controller compared with usual care: SpO2 target range was reached 90% versus 24%, 27% and 32% (P < .001) with the controller, compared with three historical control-group periods.
A specific FiO2 controller is able to maintain SpO2 reliably within a predefined target range. Two different feedback loops can be used, depending on the initial PaO2/FiO2; with both, the automatic controller showed excellent performance when compared with usual care.
Electronic supplementary material
The online version of this article (doi:10.1186/cc13734) contains supplementary material, which is available to authorized users.
PMCID: PMC4031979  PMID: 24552490
9.  Mechanical ventilation and clinical practice heterogeneity in intensive care units: a multicenter case-vignette study 
Observational studies on mechanical ventilation (MV) show practice variations across ICUs. We sought to determine, with a case-vignette study, the heterogeneity of processes of care in ICUs focusing on mechanical ventilation procedures, and whether organizational patterns or physician characteristics influence practice variations.
We conducted a cross-sectional multicenter study using the case-vignette methodology. Descriptive analyses were calculated for each organizational pattern and respondent characteristics. An Index of Qualitative Variation (IQV, from 0, no heterogeneity, to a maximum of 1) was calculated.
Forty ICUs from France (N = 33) and Switzerland (N = 7) participated; 396 physicians answered our case-vignettes. There was major heterogeneity of management processes related to MV within and across centers (mean IQV per center 0.51, SD 0.09). We observed the lowest variability (mean IQV per question < 0.4) for questions related to intubation procedure, ventilation of acute respiratory distress syndrome and the use of the semirecumbent position. We observed a high variability (mean IQV per question > 0.6) for questions related to management of endotracheal tube or suctioning, management of sedation and analgesia, and respect of autonomy. Heterogeneity was independent of respondent characteristics and of the presence of written procedures. There was a correlation between the processes associated with the highest variability (mean IQV per question > 0.6) and the annual volume of ICU admission (r = 0.32 (0.01 to 0.58)) and MV (r = 0.38 (0.07 to 0.63)). Within ICUs there was a large heterogeneity regarding knowledge of a local written procedure.
Large clinical practice variations were found among ICUs. High volume centers were more likely to have heterogeneous practices. The presence of a local written procedure or respondent characteristics did not influence practice variation.
PMCID: PMC3922080  PMID: 24484902
Mechanical ventilation; Clinical practice; Volume-outcome; Protocols
10.  Clinical review: Update on neurally adjusted ventilatory assist - report of a round-table conference 
Critical Care  2012;16(3):225.
Conventional mechanical ventilators rely on pneumatic pressure and flow sensors and controllers to detect breaths. New modes of mechanical ventilation have been developed to better match the assistance delivered by the ventilator to the patient's needs. Among these modes, neurally adjusted ventilatory assist (NAVA) delivers a pressure that is directly proportional to the integral of the electrical activity of the diaphragm recorded continuously through an esophageal probe. In clinical settings, NAVA has been chiefly compared with pressure-support ventilation, one of the most popular modes used during the weaning phase, which delivers a constant pressure from breath to breath. Comparisons with proportional-assist ventilation, which has numerous similarities, are lacking. Because of the constant level of assistance, pressure-support ventilation reduces the natural variability of the breathing pattern and can be associated with asynchrony and/or overinflation. The ability of NAVA to circumvent these limitations has been addressed in clinical studies and is discussed in this report. Although the underlying concept is fascinating, several important questions regarding the clinical applications of NAVA remain unanswered. Among these questions, determining the optimal NAVA settings according to the patient's ventilatory needs and/or acceptable level of work of breathing is a key issue. In this report, based on an investigator-initiated round table, we review the most recent literature on this topic and discuss the theoretical advantages and disadvantages of NAVA compared with other modes, as well as the risks and limitations of NAVA.
PMCID: PMC3580602  PMID: 22715815
11.  Clinical review: Respiratory monitoring in the ICU - a consensus of 16 
Critical Care  2012;16(2):219.
Monitoring plays an important role in the current management of patients with acute respiratory failure but sometimes lacks definition regarding which 'signals' and 'derived variables' should be prioritized as well as specifics related to timing (continuous versus intermittent) and modality (static versus dynamic). Many new techniques of respiratory monitoring have been made available for clinical use recently, but their place is not always well defined. Appropriate use of available monitoring techniques and correct interpretation of the data provided can help improve our understanding of the disease processes involved and the effects of clinical interventions. In this consensus paper, we provide an overview of the important parameters that can and should be monitored in the critically ill patient with respiratory failure and discuss how the data provided can impact on clinical management.
PMCID: PMC3681336  PMID: 22546221
12.  Conflicting Physiological and Genomic Cardiopulmonary Effects of Recruitment Maneuvers in Murine Acute Lung Injury 
Low tidal volume ventilation, although promoting atelectasis, is a protective strategy against ventilator-induced lung injury. Deep inflation (DI) recruitment maneuvers restore lung volumes, but potentially compromise lung parenchymal and vascular function via repetitive overdistention. Our objective was to examine cardiopulmonary physiological and transcriptional consequences of recruitment maneuvers. C57/BL6 mice challenged with either PBS or LPS via aspiration were placed on mechanical ventilation (5 h) using low tidal volume inflation (TI; 8 μl/g) alone or in combination with intermittent DIs (0.75 ml twice/min). Lung mechanics during TI ventilation significantly deteriorated, as assessed by forced oscillation technique and pressure–volume curves. DI mitigated the TI-induced alterations in lung mechanics, but induced a significant rise in right ventricle systolic pressures and pulmonary vascular resistances, especially in LPS-challenged animals. In addition, DI exacerbated the LPS-induced genome-wide lung inflammatory transcriptome, with prominent dysregulation of a gene cluster involving vascular processes, as well as increases in cytokine concentrations in bronchoalveolar lavage fluid and plasma. Gene ontology analyses of right ventricular tissue expression profiles also identified inflammatory signatures, as well as apoptosis and membrane organization ontologies, as potential elements in the response to acute pressure overload. Our results, although confirming the improvement in lung mechanics offered by DI, highlight a detrimental impact in sustaining inflammatory response and exacerbating lung vascular dysfunction, events contributing to increases in right ventricle afterload. These novel insights should be integrated into the clinical assessment of the risk/benefit of recruitment maneuver strategies.
PMCID: PMC3359949  PMID: 22135358
mechanical ventilation; microarray; pulmonary hypertension; right ventricle; acute lung injury
13.  Bench experiments comparing simulated inspiratory effort when breathing helium-oxygen mixtures to that during positive pressure support with air 
Inhalation of helium-oxygen (He/O2) mixtures has been explored as a means to lower the work of breathing of patients with obstructive lung disease. Non-invasive ventilation (NIV) with positive pressure support is also used for this purpose. The bench experiments presented herein were conducted in order to compare simulated patient inspiratory effort breathing He/O2 with that breathing medical air, with or without pressure support, across a range of adult, obstructive disease patterns.
Patient breathing was simulated using a dual-chamber mechanical test lung, with the breathing compartment connected to an ICU ventilator operated in NIV mode with medical air or He/O2 (78/22 or 65/35%). Parabolic or linear resistances were inserted at the inlet to the breathing chamber. Breathing chamber compliance was also varied. The inspiratory effort was assessed for the different gas mixtures, for three breathing patterns, with zero pressure support (simulating unassisted spontaneous breathing), and with varying levels of pressure support.
Inspiratory effort increased with increasing resistance and decreasing compliance. At a fixed resistance and compliance, inspiratory effort increased with increasing minute ventilation, and decreased with increasing pressure support. For parabolic resistors, inspiratory effort was lower for He/O2 mixtures than for air, whereas little difference was measured for nominally linear resistance. Relatively small differences in inspiratory effort were measured between the two He/O2 mixtures. Used in combination, reductions in inspiratory effort provided by He/O2 and pressure support were additive.
The reduction in inspiratory effort afforded by breathing He/O2 is strongly dependent on the severity and type of airway obstruction. Varying helium concentration between 78% and 65% has small impact on inspiratory effort, while combining He/O2 with pressure support provides an additive reduction in inspiratory effort. In addition, breathing He/O2 alone may provide an alternative to pressure support in circumstances where NIV is not available or poorly tolerated.
PMCID: PMC3527263  PMID: 23031537
Helium; Oxygen; Heliox; Inspiratory effort; Work of breathing; Airway resistance; Lung compliance; Non-invasive ventilation; Pressure support
14.  Interest of a simple on-line screening registry for measuring ICU burden related to an influenza pandemic 
Critical Care  2012;16(4):R118.
The specific burden imposed on Intensive Care Units (ICUs) during the A/H1N1 influenza 2009 pandemic has been poorly explored. An on-line screening registry allowed a daily report of ICU beds occupancy rate by flu infected patients (Flu-OR) admitted in French ICUs.
We conducted a prospective inception cohort study with results of an on-line screening registry designed for daily assessment of ICU burden.
Among the 108 centers participating to the French H1N1 research network on mechanical ventilation (REVA) - French Society of Intensive Care (SRLF) registry, 69 ICUs belonging to seven large geographical areas voluntarily participated in a website screening-registry. The aim was to daily assess the ICU beds occupancy rate by influenza-infected and non-infected patients for at least three weeks. Three hundred ninety-one critically ill infected patients were enrolled in the cohort, representing a subset of 35% of the whole French 2009 pandemic cohort; 73% were mechanically ventilated, 13% required extra corporal membrane oxygenation (ECMO) and 22% died. The global Flu-OR in these ICUs was only 7.6%, but it exceeded a predefined 15% critical threshold in 32 ICUs for a total of 103 weeks. Flu-ORs were significantly higher in University than in non-University hospitals. The peak ICU burden was poorly predicted by observations obtained at the level of large geographical areas.
The peak Flu-OR during the pandemic significantly exceeded a 15% critical threshold in almost half of the ICUs, with an uneven distribution with time, geographical areas and between University and non-University hospitals. An on-line assessment of Flu-OR via a simple dedicated registry may contribute to better match resources and needs.
PMCID: PMC3580695  PMID: 22776231
15.  Comparison of patient-ventilator interfaces based on their computerized effective dead space 
Intensive Care Medicine  2010;37(2):257-262.
Non-invasive ventilation is largely used to treat acute and chronic respiratory failure. This ventilation encounters a non negligible rate of failure related to the used interface/mask, but the reasons for this failure remain unclear. In order to shed light into this issue and to better understand the effects of the geometrical design of interfaces, we aimed to quantify flow, pressure and gas composition in terms of CO2 and O2 at the passage through different types of interface (oronasal mask, integral mask and helmet). Especially, we postulated that due to specific gas flow passing throughout interface, the effective dead space added by the interface is not always related to the whole gas volume included in the interface.
Numerical simulations, using computational fluid dynamics, were used to describe pressure, flow and gas composition during ventilation with the different interfaces.
Between the different interfaces the effective dead spaces differed only modestly (110 to 370ml) while their internal volumes were markedly different (110 to 10000ml). It was limited to half the tidal volume for the most voluminous interface, while it was close to the interface gas volume for the less voluminous interfaces. Pressure variations induced by the flow ventilation throughout the interface were negligible.
Effective dead space is not related to the internal gas volume included in the interface, suggesting that this internal volume should not be considered as a limiting factor for their efficacy during non-invasive ventilation. Patient’s comfort and synchrony have also to be taken into account.
PMCID: PMC3348871  PMID: 21063677
Computer Simulation; Equipment Design; Face; anatomy & histology; Humans; Positive-Pressure Respiration; instrumentation; Respiratory Dead Space; interfaces/masks; non-invasive ventilation; dead space
16.  Dead space and CO2 elimination related to pattern of inspiratory gas delivery in ARDS patients 
Critical Care  2012;16(2):R39.
The inspiratory flow pattern influences CO2 elimination by affecting the time the tidal volume remains resident in alveoli. This time is expressed in terms of mean distribution time (MDT), which is the time available for distribution and diffusion of inspired tidal gas within resident alveolar gas. In healthy and sick pigs, abrupt cessation of inspiratory flow (that is, high end-inspiratory flow (EIF)), enhances CO2 elimination. The objective was to test the hypothesis that effects of inspiratory gas delivery pattern on CO2 exchange can be comprehensively described from the effects of MDT and EIF in patients with acute respiratory distress syndrome (ARDS).
In a medical intensive care unit of a university hospital, ARDS patients were studied during sequences of breaths with varying inspiratory flow patterns. Patients were ventilated with a computer-controlled ventilator allowing single breaths to be modified with respect to durations of inspiratory flow and postinspiratory pause (TP), as well as the shape of the inspiratory flow wave. From the single-breath test for CO2, the volume of CO2 eliminated by each tidal breath was derived.
A long MDT, caused primarily by a long TP, led to importantly enhanced CO2 elimination. So did a high EIF. Effects of MDT and EIF were comprehensively described with a simple equation. Typically, an efficient and a less-efficient pattern of inspiration could result in ± 10% variation of CO2 elimination, and in individuals, up to 35%.
In ARDS, CO2 elimination is importantly enhanced by an inspiratory flow pattern with long MDT and high EIF. An optimal inspiratory pattern allows a reduction of tidal volume and may be part of lung-protective ventilation.
PMCID: PMC3964798  PMID: 22390777
17.  Results of noninvasive ventilation in very old patients 
Noninvasive ventilation (NIV) is frequently used for the management of acute respiratory failure (ARF) in very old patients (≥ 80 years), often in the context of a do-not-intubate order (DNI). We aimed to determine its efficacy and long-term outcome.
Prospective cohort of all patients admitted to the medical ICU of a tertiary hospital during a 2-year period and managed using NIV. Characteristics of patients, context of NIV, and treatment intensity were compared for very old and younger patients. Six-month survival and functional status were assessed in very old patients.
During the study period, 1,019 patients needed ventilatory support and 376 (37%) received NIV. Among them, 163 (16%) very old patients received ventilatory support with 60% of them managed using NIV compared with 32% of younger patients (p < 0.0001). Very old patients received NIV more frequently with DNI than in younger patients (40% vs. 8%). Such cases were associated with high mortality for both very old and younger patients. Hospital mortality was higher in very old than in younger patients but did not differ when NIV was used for cardiogenic pulmonary edema or acute-on-chronic respiratory failure (20% vs. 15%) and in postextubation (15% vs. 17%) out of a context of DNI. Six-month mortality was 51% in very old patients, 67% for DNI patients, and 77% in case of NIV failure and endotracheal intubation. Of the 30 hospital survivors, 22 lived at home and 13 remained independent for activities of daily living.
Very old patients managed using NIV have an overall satisfactory 6-month survival and functional status, except for endotracheal intubation after NIV failure.
PMCID: PMC3306189  PMID: 22353636
18.  Accuracy and precision of end-expiratory lung-volume measurements by automated nitrogen washout/washin technique in patients with acute respiratory distress syndrome 
Critical Care  2011;15(6):R294.
End-expiratory lung volume (EELV) is decreased in acute respiratory distress syndrome (ARDS), and bedside EELV measurement may help to set positive end-expiratory pressure (PEEP). Nitrogen washout/washin for EELV measurement is available at the bedside, but assessments of accuracy and precision in real-life conditions are scant. Our purpose was to (a) assess EELV measurement precision in ARDS patients at two PEEP levels (three pairs of measurements), and (b) compare the changes (Δ) induced by PEEP for total EELV with the PEEP-induced changes in lung volume above functional residual capacity measured with passive spirometry (ΔPEEP-volume). The minimal predicted increase in lung volume was calculated from compliance at low PEEP and ΔPEEP to ensure the validity of lung-volume changes.
Thirty-four patients with ARDS were prospectively included in five university-hospital intensive care units. ΔEELV and ΔPEEP volumes were compared between 6 and 15 cm H2O of PEEP.
After exclusion of three patients, variability of the nitrogen technique was less than 4%, and the largest difference between measurements was 81 ± 64 ml. ΔEELV and ΔPEEP-volume were only weakly correlated (r2 = 0.47); 95% confidence interval limits, -414 to 608 ml). In four patients with the highest PEEP (≥ 16 cm H2O), ΔEELV was lower than the minimal predicted increase in lung volume, suggesting flawed measurements, possibly due to leaks. Excluding those from the analysis markedly strengthened the correlation between ΔEELV and ΔPEEP volume (r2 = 0.80).
In most patients, the EELV technique has good reproducibility and accuracy, even at high PEEP. At high pressures, its accuracy may be limited in case of leaks. The minimal predicted increase in lung volume may help to check for accuracy.
PMCID: PMC3388680  PMID: 22166727
19.  Impact of acute hypercapnia and augmented positive end-expiratory pressure on right ventricle function in severe acute respiratory distress syndrome 
Intensive Care Medicine  2009;35(11):1850-1858.
To evaluate the effects of acute hypercapnia induced by positive end-expiratory pressure (PEEP) variations at constant plateau pressure (Pplat) in patients with severe acute respiratory distress syndrome (ARDS) on right (R) and left ventricular (LV) function.
Prospective observational study in two academic intensive care units enrolling 11 adults with severe ARDS (PaO2/FiO2<150 mm Hg at PEEP >5 cm H2O). We compared three ventilatory strategies, each used for 1 hour, with Pplat at 22 [20–25] cm H2O: low PEEP (5.4 cm H2O) or high PEEP (11.0 cm H2O) with compensation of the tidal volume reduction by either a high respiratory rate (high PEEP/high rate) or instrumental dead space decrease (high PEEP/low rate). We assessed RV function (transesophageal echocardiography), alveolar dead space (expired CO2), and alveolar recruitment (pressure-volume curves).
Compared to low PEEP, PaO2/FiO2 ratio and alveolar recruitment were increased with high PEEP. Alveolar dead space remained unchanged. Both high-PEEP strategies induced higher PaCO2 levels (71 [60–94] and 75 [53–84], vs. 52 [43–68] mm Hg) and lower pH values (7.17 [7.12–7.23] and 7.20 [7.16–7.25] vs. 7.30 [7.24–7.35]), as well as a significant decrease in cardiac index, RV dilatation and LV deformation. The decrease in stroke index tended to be negatively correlated to the increase in alveolar recruitment with high PEEP.
Acidosis and hypercapnia induced by tidal volume reduction and increase in PEEP at constant Pplat was associated with impaired RV function and hemodynamics despite a positive effect on oxygenation and alveolar recruitment.
PMCID: PMC3206087  PMID: 19652953
Acidosis, Respiratory; etiology; Acute Disease; Aged; Analysis of Variance; Echocardiography, Transesophageal; Female; Humans; Hypercapnia; diagnosis; etiology; Intensive Care; methods; Linear Models; Male; Middle Aged; Positive-Pressure Respiration; adverse effects; methods; Prospective Studies; Respiratory Dead Space; Respiratory Distress Syndrome, Adult; complications; metabolism; physiopathology; therapy; Respiratory Rate; Severity of Illness Index; Statistics, Nonparametric; Tidal Volume; Ventricular Dysfunction, Right; diagnosis; etiology; lung injury; acidosis; right heart; alveolar recruitment; alveolar dead space
20.  Diagnostic performance of fractional excretion of urea in the evaluation of critically ill patients with acute kidney injury: a multicenter cohort study 
Critical Care  2011;15(4):R178.
Several factors, including diuretic use and sepsis, interfere with the fractional excretion of sodium, which is used to distinguish transient from persistent acute kidney injury (AKI). These factors do not affect the fractional excretion of urea (FeUrea). However, there are conflicting data on the diagnostic accuracy of FeUrea.
We conducted an observational, prospective, multicenter study at three ICUs in university hospitals. Unselected patients, except those with obstructive AKI, were admitted to the participating ICUs during a six-month period. Transient AKI was defined as AKI caused by renal hypoperfusion and reversal within three days. The results are reported as medians (interquartile ranges).
A total of 203 patients were included. According to our definitions, 67 had no AKI, 54 had transient AKI and 82 had persistent AKI. FeUrea was 39% (28 to 40) in the no-AKI group, 41% (29 to 54) in the transient AKI group and 32% (22 to 51) in the persistent AKI group (P = 0.12). FeUrea was of little help in distinguishing transient AKI from persistent AKI, with the area under the receiver operating characteristic curve being 0.59 (95% confidence interval, 0.49 to 0.70; P = 0.06). Sensitivity was 63% and specificity was 54% with a cutoff of 35%. In the subgroup of patients receiving diuretics, the results were similar.
FeUrea may be of little help in distinguishing transient AKI from persistent AKI in critically ill patients, including those receiving diuretic therapy. Additional studies are needed to evaluate alternative markers or strategies to differentiate transient from persistent AKI.
PMCID: PMC3387621  PMID: 21794161
acute kidney failure; ICU; fractional excretion of sodium; acute tubular necrosis; diuretics; sensitivity and specificity
21.  An updated study-level meta-analysis of randomised controlled trials on proning in ARDS and acute lung injury 
Critical Care  2011;15(1):R6.
In patients with acute lung injury (ALI) and/or acute respiratory distress syndrome (ARDS), recent randomised controlled trials (RCTs) showed a consistent trend of mortality reduction with prone ventilation. We updated a meta-analysis on this topic.
RCTs that compared ventilation of adult patients with ALI/ARDS in prone versus supine position were included in this study-level meta-analysis. Analysis was made by a random-effects model. The effect size on intensive care unit (ICU) mortality was computed in the overall included studies and in two subgroups of studies: those that included all ALI or hypoxemic patients, and those that restricted inclusion to only ARDS patients. A relationship between studies' effect size and daily prone duration was sought with meta-regression. We also computed the effects of prone positioning on major adverse airway complications.
Seven RCTs (including 1,675 adult patients, of whom 862 were ventilated in the prone position) were included. The four most recent trials included only ARDS patients, and also applied the longest proning durations and used lung-protective ventilation. The effects of prone positioning differed according to the type of study. Overall, prone ventilation did not reduce ICU mortality (odds ratio = 0.91, 95% confidence interval = 0.75 to 1.2; P = 0.39), but it significantly reduced the ICU mortality in the four recent studies that enrolled only patients with ARDS (odds ratio = 0.71; 95% confidence interval = 0.5 to 0.99; P = 0.048; number needed to treat = 11). Meta-regression on all studies disclosed only a trend to explain effect variation by prone duration (P = 0.06). Prone positioning was not associated with a statistical increase in major airway complications.
Long duration of ventilation in prone position significantly reduces ICU mortality when only ARDS patients are considered.
PMCID: PMC3222033  PMID: 21211010
22.  Effects of inspiratory pause on CO2 elimination and arterial PCO2 in acute lung injury 
Journal of Applied Physiology  2008;105(6):1944-1949.
A high respiratory rate associated with the use of small tidal volumes, recommended for acute lung injury (ALI), shortens time for gas diffusion in the alveoli. This may decrease CO2 elimination. We hypothesized that a post-inspiratory pause could enhance CO2 elimination and reduce PaCO2 by reducing dead space in ALI. In 15 mechanically ventilated patients with ALI and hypercapnia, a 20% post-inspiratory pause (Tp20) was applied during a period of 30 min between two ventilation periods without post-inspiratory pause (Tp0). Other parameters were kept unchanged. The single breath test for CO2 was recorded every 5 minutes to measure tidal CO2 elimination (VtCO2), airway dead space (VDaw) and slope of the alveolar plateau. PaO2, PaCO2, physiological and alveolar dead space (VDphys, VDalv) were determined at the end of each 30 minute period. The post-inspiratory pause, 0.7±0.2 s, induced on average less than 0.5 cm H2O of intrinsic PEEP. During Tp20, VtCO2 increased immediately by 28±10% (14±5 ml per breath compared to 11±4 for Tp0) and then decreased without reaching the initial value within 30 minutes. The addition of a post-inspiratory pause decreased significantly VDaw by 14% and VDphys by 11% with no change in VDalv. During Tp20, the slope of alveolar plateau initially fell to 65±10 % of baseline value and continued to decrease. Tp20 induced a 10±3% decrease in PaCO2 at 30 minutes (from 55±10 to 49±9 mmHg, p<0.001) with no significant variation in PaO2. Post-inspiratory pause has a significant influence on CO2 elimination when small tidal volumes are used during mechanical ventilation for ALI.
PMCID: PMC2956750  PMID: 18801962
Adult; Aged; Aged, 80 and over; Blood Gas Analysis; Carbon Dioxide; blood; metabolism; Female; Humans; Lung Diseases; metabolism; physiopathology; Male; Middle Aged; Pneumonia; metabolism; physiopathology; Positive-Pressure Respiration; Respiration, Artificial; Respiratory Dead Space; physiology; Respiratory Distress Syndrome, Adult; metabolism; physiopathology; Respiratory Mechanics; physiology; Tidal Volume; physiology; Gas Exchange; Dead Space; Mechanical Ventilation; ARDS
23.  A bench study of intensive-care-unit ventilators: new versus old and turbine-based versus compressed gas-based ventilators 
Intensive Care Medicine  2009;35(8):1368-1376.
To compare 13 commercially available, new-generation, intensive-care-unit (ICU) ventilators regarding trigger function, pressurization capacity during pressure-support ventilation (PSV), accuracy of pressure measurements and expiratory resistance.
Design and Setting
Bench study at a research laboratory in a university hospital.
Four turbine-based ventilators and nine conventional servo-valve compressed-gas ventilators were tested using a two-compartment lung model.
Three levels of effort were simulated. Each ventilator was evaluated at four PSV levels (5, 10, 15, and 20 cm H2O), with and without positive end-expiratory pressure (5 cm H2O, Trigger function was assessed as the time from effort onset to detectable pressurization. Pressurization capacity was evaluated using the airway pressure-time product computed as the net area under the pressure-time curve over the first 0.3 s after inspiratory effort onset. Expiratory resistance was evaluated by measuring trapped volume in controlled ventilation. Significant differences were found across the ventilators, with a range of triggering-delay from 42 ms to 88 ms for all conditions averaged (P<.001). Under difficult conditions, the triggering delay was longer than 100 ms and the pressurization was poor with five ventilators at PSV5 and three at PSV10, suggesting an inability to unload patient’s effort. On average, turbine-based ventilators performed better than conventional ventilators, which showed no improvement compared to a 2000 bench comparison.
Technical performances of trigger function, pressurization capacity and expiratory resistance vary considerably across new-generation ICU ventilators. ICU ventilators seem to have reached a technical ceiling in recent years, and some ventilators still perform inadequately.
PMCID: PMC2873304  PMID: 19352622
Equipment Design; Hospitals, University; Humans; Intensive Care Units; Models, Biological; Respiration, Artificial; instrumentation; standards; Work of Breathing; physiology; Mechanical ventilation; Pressure-support ventilation; Work of breathing; Inspiratory trigger; Bench study
24.  Colloid-induced kidney injury: experimental evidence may help to understand mechanisms 
Critical Care  2009;13(2):130.
Fluid resuscitation is widely used, and many patients are therefore exposed to plasma volume expanders. Among these, colloids, particularly hydroxyethyl starches, have been shown in recent experiments and clinical studies to induce acute kidney injury. The mechanisms of colloid-induced acute kidney injury remain incompletely elucidated. The risks associated with colloid osmotic pressure elevation in vivo and the high incidence of osmotic nephrosis lesions in experimental models and clinical studies indicate that hydroxyethyl starches can no longer be considered safe.
PMCID: PMC2689470  PMID: 19435473
25.  Noninvasive ventilation: A survey of practice patterns of its use in India 
Background and Aims:
To understand the practice patterns of noninvasive ventilation (NIV) use by Indian physicians.
Subjects and Methods:
Around three thousand physicians from all over India were mailed a questionnaire that could capture the practice patterns of NIV use.
Completed responses were received from 648 physicians (21.6%). Majority (n = 469, 72.4%, age 40 ± 9 years, M:F 409:60) use NIV in their clinical practice. NIV was most exclusively being used in the ICU setting (68.4%) and the commonest indication for its use was chronic obstructive pulmonary disease (COPD) (71.4%). A significant number did not report use of a conventional ventilator for NIV support (62%). Oronasal mask was the overwhelming favorite among the sampled physicians (68.2%). In most of the cases, the treating physician initiated NIV (60.8%) and a baseline blood gas analysis was performed in only 71.1% of the cases (315/443). Nasal bridge pressure sores was the commonest complication (64.2%).
NIV is being widely used in clinical practice in India for various indications. COPD is the most common indication for its deployment. There seems to be a marked variability in the patterns relating to actual deployment of NIV, including the site of initiation, protocols for initiation followed, and monitoring of patients.
PMCID: PMC2738320  PMID: 19742261
Noninvasive ventilation; questionnaire-based study; survey

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