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Purpose Invasive pulmonary aspergillosis (IPA) is a dreadful event in patients with hematological malignancies (HM). Recent advances have standardized diagnostic, prophylactic and curative therapeutic strategies. We sought to assess whether these advances actually translate into improved survival in critically ill patients with acute respiratory failure and IPA. Methods This was a retrospective, multicenter study. Adult patients with HM, IPA, admitted to the ICU for acute respiratory failure over a 20-year period (January 1998-December 2017) were included. A cox regression model was used to identify variables independently associated with day-90 survival. Results Overall, 219 patients were included [138 (63%) men, median age 55 (IQR 44-64)]. Acute myeloid leukemia (30.1%) and non-Hodgkin lymphoma (22.8%) were the most frequent malignancies, and 53 (24.2%) were allogeneic stem cell recipients. Day-1 SOFA score was 9 [7 (See CR7)-12 (See CR12)]. Most patients presented with probable IPA, whereas 15 (7%) underwent lung biopsies or pleurocentesis and met criteria for proven IPA. Overall ICU and day-90 mortality were, respectively, 58.4% and 75.2% (80.4% if invasive mechanical ventilation) without any significant improvement over time. By multivariable analysis adjusted on day-1 SOFA score and ventilation strategies, voriconazole use (HR 0.49, CI 95 0.34-0.73, p < 0.001) and an ICU admission after 2010 (HR 0.67, 0.45-0.99, p = 0.042) were associated with increased survival, whereas a diffuse radiologic pattern (HR 2.07, CI 95 1.33-3.24, p = 0.001) and delayed admission to the ICU (HR 1.51, CI 95 1.05-2.16, p = 0.026) were independently associated with increased mortality. Conclusions IPA is associated with high mortality rates in critically ill patients with acute respiratory failure. Routine voriconazole and prompt ICU admission are warranted., Author(s): Emmanuel Pardo [sup.1], Virginie Lemiale [sup.1], Djamel Mokart [sup.2], Annabelle Stoclin [sup.3], Anne-Sophie Moreau [sup.4], Lionel Kerhuel [sup.1], Laure Calvet [sup.1], Sandrine Valade [sup.1], Audrey De Jong [sup.1], Michael [...]

Purpose Extent of lung contusion on initial computed tomography (CT) scan predicts the occurrence of acute respiratory distress syndrome (ARDS) in blunt chest trauma patients. We hypothesized that lung ultrasonography (LUS) on admission could also predict subsequent ARDS. Methods Forty-five blunt trauma patients were prospectively studied. Clinical examination, chest radiography, and LUS were performed on arrival at the emergency room. Lung contusion extent was quantified using a LUS score and compared to CT scan measurements. The ability of the LUS score to predict ARDS was tested using the area under the receiver operating characteristic curve (AUC-ROC). The diagnostic accuracy of LUS was compared to that of combined clinical examination and chest radiography for pneumothorax, lung contusion, and hemothorax, with thoracic CT scan as reference. Results Lung contusion extent assessed by LUS on admission was predictive of the occurrence of ARDS within 72 h (AUC-ROC = 0.78 [95 % CI 0.64-0.92]). The extent of lung contusion on LUS correlated well with CT scan measurements (Spearman's coefficient = 0.82). A LUS score of 6 out of 16 was the best threshold to predict ARDS, with a 58 % [95 % CI 36-77] sensitivity and a 96 % [95 % CI 76-100] specificity. The diagnostic accuracy of LUS was higher than that of combined clinical examination and chest radiography: (AUC-ROC) 0.81 [95 % CI 0.50-1.00] vs. 0.74 [0.48-1.00] (p = 0.24) for pneumothorax, 0.88 [0.76-1.00] vs. 0.69 [0.47-0.92] (p < 0.05) for lung contusion, and 0.84 [0.59-1.00] vs. 0.73 [0.51-0.94] (p < 0.05) for hemothorax. Conclusions LUS on admission identifies patients at risk of developing ARDS after blunt trauma. In addition, LUS allows rapid and accurate diagnosis of common traumatic thoracic injuries., Author(s): Damien Leblanc [sup.1], Clément Bouvet [sup.1], Franck Degiovanni [sup.1], Cosmina Nedelcu [sup.2], Guillaume Bouhours [sup.1], Emmanuel Rineau [sup.1], Catherine Ridereau-Zins [sup.2], Laurent Beydon [sup.1], Sigismond Lasocki [sup.1] Author Affiliations: [...]

Purpose There is still a lack of evidence to support the use of specific anesthetic agents during major operations that could affect the development of postoperative acute lung injury (ALI). This study determined the protective effect of inhaled isoflurane in a rat model of endotoxin-induced ALI. Methods Rats were exposed to volatile isoflurane (1.5 % in oxygen) or pure oxygen via a facemask for 2 h. After a 3-h recovery period, rats were reanesthetized and ALI was induced by intratracheal instillation of lipopolysaccharide (LPS, 1 mg/kg in 0.5 ml saline). In some animals, a specific inducible nitric oxide synthase (iNOS) inhibitor, 1400W, (10 mg/kg, i.p.) was administered before exposure to isoflurane. Animals were sacrificed 12 h later for analysis. Pulmonary artery vasomotor function and alveolocapillary permeability were assessed. Expression of iNOS and CD11b, and activity of myeloperoxidase in the lung were analyzed. Results The maximal relaxation response to acetylcholine was significantly potentiated in rats pretreated with isoflurane. Lung wet-to-dry ratio was reduced in the lung of isoflurane-treated animals. Expression of iNOS and CD11b were attenuated in the lung tissue obtained from rats receiving isoflurane. Furthermore, enzymatic activity of myeloperoxidase was also reduced in the lung preexposed to isoflurane. However, these pulmonary protective effects of isoflurane were significantly abolished by pretreatment with 1400W. Conclusion Pretreatment with volatile isoflurane attenuated inflammatory process in the lung tissue of rats with LPS-induced ALI, and this preconditioning pulmonary protective effect was mainly mediated by activation of endogenous iNOS in the lung. Keywords Inhaled anesthetics * Endotoxin * Myeloperoxidase * Inflammation, Introduction Acute lung injury (ALI) and the subsequent acute respiratory distress syndrome (ARDS) are not uncommonly developed in the postanesthesia period, especially in patients with sepsis, multiple trauma/fracture, massive blood [...]

The case of a 23-year old man who got a bug bite on his left calf is discussed to arrive at a better understanding of the causes, symptoms and diagnosis of refractory hypoxemia in acute respiratory distress syndrome (ARDS). The different treatment methodologies and management regime for the same are highlighted.

Byline: Thomas V. Brogan (1), Ravi R. Thiagarajan (2), Peter T. Rycus (3), Robert H. Bartlett (4), Susan L. Bratton (5) Keywords: Extracorporeal Life Support Organization (ELSO); Acute respiratory distress syndrome (ARDS); Pneumonia; Survival; Complications Abstract: Objective To evaluate clinical and treatment factors for patients recorded in the Extracorporeal Life Support Organization (ELSO) registry and survival of adult extracorporeal membrane oxygenation (ECMO) respiratory failure patients. Design and patients Retrospective case review of the ELSO registry from 1986--2006. Data were analyzed separately for the entire time period and the most recent years (2002--2006). Results Of 1,473 patients, 50% survived to discharge. Median age was 34 years. Most patients (78%) were supported with venovenous ECMO. In a multi-variate logistic regression model, pre-ECMO factors including increasing age, decreased weight, days on mechanical ventilation before ECMO, arterial blood pH a$? 7.18, and Hispanic and Asian race compared to white race were associated with increased odds of death. For the most recent years (n = 600), age and PaCO.sub.2 aY= 70 compared to PaCO.sub.2 a$? 44 were also associated with increased odds of death. The two diagnostic categories acute respiratory failure and asthma compared to ARDS were associated with decreased odds of mortality as was venovenous compared to venoarterial mode. CPR and complications while on ECMO including circuit rupture, central nervous system infarction or hemorrhage, gastrointestinal or pulmonary hemorrhage, and arterial blood pH < 7.2 or >7.6 were associated with increased odds of death. Conclusions Survival among this cohort of adults with severe respiratory failure supported with ECMO was 50%. Advanced patient age, increased pre-ECMO ventilation duration, diagnosis category and complications while on ECMO were associated with mortality. Prospective studies are needed to evaluate the role of this complex support mode. Author Affiliation: (1) Division of Critical Care Medicine, Department of Pediatrics, Seattle Children's Hospital, University of Washington School of Medicine, Seattle, WA, USA (2) Department of Cardiology and Pediatrics, Children's Hospital, Harvard Medical School, Boston, MA, USA (3) Extracorporeal Life Support Organization, Ann Arbor, MI, USA (4) Department of Surgery, University of Michigan Health System, Ann Arbor, MI, USA (5) Department of Pediatrics, Primary Children's Medical Center, University of Utah, Salt Lake City, UT, USA Article History: Registration Date: 09/09/2009 Received Date: 14/01/2009 Accepted Date: 27/07/2009 Online Date: 22/09/2009

Byline: Raffaele L. Dellaca (1), Marie Andersson Olerud (2), Emanuela Zannin (1), Peter Kostic (2), Pasquale P. Pompilio (1), Goran Hedenstierna (3), Antonio Pedotti (1), Peter Frykholm (2) Keywords: Forced oscillation technique; ALI/ARDS; Mechanical ventilation; PEEP; Respiratory mechanics Abstract: Purpose ALI and ARDS are associated with lung volume derecruitment, usually counteracted by PEEP and recruitment maneuvers (RM), which should be accurately tailored to the patient's needs. The aim of this study was to investigate the possibility of monitoring the amount of derecruited lung by the forced oscillation technique (FOT). Methods We studied six piglets (26 +- 2.5 kg) ventilated by a mechanical ventilator connected to a FOT device that produced sinusoidal pressure forcing at 5 Hz. The percentage of non-aerated lung tissue (V tiss.sub.NA%) was measured by whole-body CT scans at end-expiration with zero end-expiratory pressure. Respiratory system oscillatory input reactance (X .sub.rs) was measured simultaneously to CT and used to derive oscillatory compliance (C .sub.X5), which we used as an index of recruited lung. Measurements were performed at baseline and after several interventions in the following sequence: mono-lateral reabsorption atelectasis, RM, bi-lateral derecruitment induced by broncho-alveolar lavage and a second RM. Results By pooling data from all experimental conditions and all pigs, C .sub.X5 was linearly correlated to V tiss.sub.NA% (r .sup.2 = 0.89) regardless of the procedure used to de-recruit the lung (reabsorption atelectasis or pulmonary lavage). Separate correlation analysis on single pigs showed similar regression equations, with an even higher coefficient of determination (r .sup.2 = 0.91 +- 0.07). Conclusion These results suggest that FOT and the measurement of C .sub.X5 could be a useful tool for the non-invasive measurement of lung volume recruitment/derecruitment. Author Affiliation: (1) Dipartimento di Bioingegneria, Politecnico di Milano University, Piazza Leonardo da Vinci 32, 20133, Milan, Italy (2) Department of Surgical Sciences, Anaesthesia and Intensive Care, Uppsala University, Uppsala, Sweden (3) Department of Medical Sciences, Clinical Physiology, Uppsala University, Uppsala, Sweden Article History: Registration Date: 10/09/2009 Received Date: 19/01/2009 Accepted Date: 02/09/2009 Online Date: 30/09/2009 Article note: Electronic supplementary material The online version of this article (doi: 10.1007/s00134-009-1673-3) contains supplementary material, which is available to authorized users.

The study attempts to investigate all patients with 2009 influenza A (H1N1) acute respiratory distress syndrome that were treated with extracorporeal membrane oxygenation (ECMO) and the outcomes of treatment. The results indicated that patients treated with ECMO were mostly young adults with severe hypoxemia that had a 21% mortality rate.

Byline: Marco Piastra (1), Daniele Luca (1), Domenico Pietrini (1), Silvia PulitanA2 (1), Sonia D'Arrigo (1), Aldo Mancino (1), Giorgio Conti (1) Keywords: Noninvasive ventilation; Children; PICU; ARDS Abstract: Objective To verify the feasibility of non-invasive ventilation (NIV) in immunocompromised children affected by ARDS. Setting University Hospital PICU. Patients Twenty-three consecutive immunocompromised children treated with NIV for ARDS. Interventions All consecutive patients received NIV through a face-mask or a helmet. Results No differences were found regarding admission data and severity scores between NIV responders and non-responders. Early and sustained improvement in PaO.sub.2/FiO.sub.2 ratio were observed in 82 and 74% of cases, respectively. 13 out of 23 patients (54.5%) avoided intubation and were discharged from the PICU ten patients required intubation: two of them survived and eight patients died (two refractory hypoxemia, three septic shock, three multi-organ failure). PICU and intra-hospital mortality was significantly higher for NIV-nonresponders (P < 0.001). PICU stay was significantly shorter for NIV responders (P = 0.03). NIV responders had significantly lower heart and respiratory rate at the end of treatment (P < 0.001 and P = 0.048, respectively). Conclusions NIV administration is feasible and well tolerated in immunocompromised children with ARDS. A short NIV trial can be used to verify the usefulness of the technique. A randomized controlled trial is needed to confirm the efficacy of NIV in immunocompromised children requiring ventilatory support for ARDS. Author Affiliation: (1) Pediatric Intensive Care Unit, Department of Anaesthesiology and Intensive Care, Catholic University of the Sacred Heart, University Hospital 'A.Gemelli', L.go A. Gemelli 8, 00168, Rome, Italy Article History: Registration Date: 10/06/2009 Received Date: 20/10/2008 Accepted Date: 09/06/2009 Online Date: 23/06/2009 Article note: Partial results from this study were presented at the 9th European Pediatric and Neonatal Ventilation Conference (EPNV 2008), held in Montreux (Switzerland), April 2008. Electronic supplementary material The online version of this article (doi: 10.1007/s00134-009-1558-5) contains supplementary material, which is available to authorized users.

Byline: Rita Linko (1), Marjatta Okkonen (1), Ville Pettila (2), Juha Perttila (3), Ilkka Parviainen (4), Esko Ruokonen (4), Jyrki Tenhunen (5), Tero Ala-Kokko (6), Tero Varpula (1) Keywords: Acute respiratory failure; Acute lung injury; Acute respiratory distress syndrome; Mechanical ventilation; Outcome Abstract: Objective To evaluate the incidence, treatment and mortality of acute respiratory failure (ARF) in Finnish intensive care units (ICUs). Study design Prospective multicentre cohort study. Methods All adult patients in 25 ICUs were screened for use of invasive or non-invasive ventilatory support during an 8-week period. Patients needing ventilatory support for more than 6 h were included and defined as ARF patients. Risk factors for ARF and details of prior chronic health status were assessed. Ventilatory and concomitant treatments were evaluated and recorded daily throughout the ICU stay. ICU and 90-day mortalities were assessed. Results A total of 958 (39%) from the 2,473 admitted patients were treated with ventilatory support for more than 6 h. Incidence of ARF, acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) was 149.5, 10.6 and 5.0/100,000 per year, respectively. Ventilatory support was started with non-invasive interfaces in 183 of 958 (19%) patients. Ventilatory modes allowing triggering of spontaneous breaths were preferred (81%). Median tidal volume/predicted body weight was 8.7 (7.6--9.9) ml/kg and plateau pressure 19 (16--23) cm[H.sub.2]O. The 90-day mortality of ARF was 31%. Conclusions While the incidence of ARF requiring ventilatory support is higher, the incidence of ALI and ARDS seems to be lower in Finland than previously reported in other countries. Tidal volumes are higher than recommended in the concept of lung protective strategy. However, restriction of peak airway pressure was used in the majority of ARF patients. Author Affiliation: (1) Intensive Care Units, Department of Anaesthesia and Intensive Care Medicine, Division of Surgery, Helsinki University Hospital, Helsinki, Finland (2) Department of Epidemiology and Preventive Medicine, Australian and New Zealand Intensive Care Research Center, Monash University, Melbourne, Australia (3) Department of Anesthesia and Intensive Care Medicine, Turku University Hospital, Turku, Finland (4) Division of Intensive Care, Kuopio University Hospital, Kuopio, Finland (5) Department of Intensive Care Medicine, Critical Care Medicine Research Group, Tampere University Hospital, Tampere, Finland (6) Division of Intensive Care, Department of Anesthesiology, Oulu University Hospital, Oulu, Finland Article History: Registration Date: 28/05/2009 Received Date: 14/01/2009 Accepted Date: 07/05/2009 Online Date: 13/06/2009 Article note: This article is discussed in the editorial available at: doi: 10.1007/s00134-009-1518-0. Electronic supplementary material The online version of this article (doi: 10.1007/s00134-009-1519-z) contains supplementary material, which is available to authorized users.

Byline: Robinder G. Khemani (1,2), David Conti (2), Todd A. Alonzo (2), Robert D. Bart (1,2), Christopher J. L. Newth (1,2) Keywords: Pediatrics; Positive pressure respiration; Lung volume measurements Abstract: Objectives To determine if tidal volume (V .sub.T) between 6 and 10 ml/kg body weight using pressure control ventilation affects outcome for children with acute hypoxemic respiratory failure (AHRF) or acute lung injury (ALI). To validate lung injury severity markers such as oxygenation index (OI), PaO.sub.2/FiO.sub.2 (PF) ratio, and lung injury score (LIS). Design Retrospective, January 2000--July 2007. Setting Tertiary care, 20-bed PICU. Patients Three hundred and ninety-eight endotracheally intubated and mechanically ventilated children with PF ratio Measurements and main results Three hundred and ninety-eight children met study criteria, with 20% mortality. 192 children had ALI. Using >90% pressure control ventilation, 85% of patients achieved V .sub.T less than 10 ml/kg. Median V .sub.T was not significantly different between survivors and non-survivors during the first 3 days of mechanical ventilation. After controlling for diagnostic category, age, delta P (PIP-PEEP), PEEP, and severity of lung disease, V .sub.T was not associated with mortality (P > 0.1), but higher V .sub.T at baseline and on day 1 of mechanical ventilation was associated with more ventilator free days (P < 0.05). This was particularly seen in patients with better respiratory system compliance [Crs > 0.5 ml/cmH.sub.20/kg, OR = 0.70 (0.52, 0.95)]. OI, PF ratio, and LIS were all associated with mortality (P < 0.05). Conclusions When ventilating children using lung protective strategies with pressure control ventilation, observed V .sub.T is between 6 and 10 ml/kg and is not associated with increased mortality. Moreover, higher V .sub.T within this range is associated with more ventilator free days, particularly for patients with less severe disease. Author Affiliation: (1) Department of Anesthesia and Critical Care Medicine, Children's Hospital Los Angeles, 4650 Sunset Blvd, Mail Stop 12, Los Angeles, CA, 90027, USA (2) Keck School of Medicine, University of Southern California, Los Angeles, CA, USA Article History: Registration Date: 28/05/2009 Received Date: 11/09/2008 Accepted Date: 05/04/2009 Online Date: 17/06/2009 Article note: Electronic supplementary material The online version of this article (doi: 10.1007/s00134-009-1527-z) contains supplementary material, which is available to authorized users.

Byline: Vitaly Herasevich (1), Murat Yilmaz (1,3), Hasrat Khan (1,2), Rolf D. Hubmayr (1), Ognjen Gajic (1) Keywords: Respiratory distress syndrome; Adult; Syndrome surveillance; Database; Datamart; Diagnosis Abstract: Objective Early detection of acute lung injury (ALI) is essential for timely implementation of evidence-based therapies and enrollment into clinical trials. We aimed to determine the accuracy of computerized syndrome surveillance for detection of ALI in hospitalized patients and compare it with routine clinical assessment. Design Using a near-real time copy of the electronic medical records, we developed and validated a custom ALI electronic alert (ALI 'sniffer') based on the European-American Consensus Conference Definition and compared its performance against provider-derived documentation. Patients and setting A total of 3,795 consecutive critically ill patients admitted to nine multidisciplinary intensive care units (ICUs) of a tertiary care teaching institution were included. Measurements and main results ALI developed in 325 patients and was recognized by bedside clinicians in only 86 (26.5%). Under-recognition of ALI was associated with not implementing protective mechanical ventilation (median tidal volumes of 9.2 vs. 8.0 ml/kg predicted body weight, P < 0.001). ALI 'sniffer' demonstrated excellent sensitivity of 96% (95% CI 94--98) and moderate specificity of 89% (95% CI 88--90) with a positive predictive value ranging from 24% (95% CI 13--40) in the heart--lung transplant ICU to 64% (95% CI 55--71) in the medical ICU. Conclusions The computerized surveillance system accurately identifies critically ill patients who develop ALI syndrome. Since the lack of ALI recognition is a barrier to the timely implementation of best practices and enrollment into research studies, computerized syndrome surveillance could be a useful tool to enhance patient safety and clinical research. Author Affiliation: (1) Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Mayo Clinic College of Medicine, 200 First Street SW, Rochester, MN, 55905, USA (2) Department of Critical Care Services, MeritCare Medical Center, 801 Broadway N, Fargo, ND, 58122, USA (3) Department of Anesthesiology and Intensive Care, Medical Faculty, Akdeniz University (MY), Antalya, Turkey Article History: Registration Date: 04/03/2009 Received Date: 17/07/2008 Accepted Date: 16/11/2008 Online Date: 12/03/2009

Byline: Alessandro Protti (1), Davide Chiumello (1), Massimo Cressoni (1), Eleonora Carlesso (1), Cristina Mietto (1), Virna Berto (1), Marco Lazzerini (2), Michael Quintel (3), Luciano Gattinoni (1) Keywords: Acute lung injury; Acute respiratory distress syndrome; Prone position; Recruitment; Carbon dioxide; Computed tomography Abstract: Purpose To clarify whether the gas exchange response to prone position is associated with lung recruitability in mechanically ventilated patients with acute respiratory failure. Methods In 32 patients, gas exchange response to prone position was investigated as a function of lung recruitability, measured by computed tomography in supine position. Results No relationship was found between increased oxygenation in prone position and lung recruitability. In contrast, the decrease of PaCO.sub.2 was related with lung recruitability (R .sup.2 0.19 P = 0.01). Patients who decreased their PaCO.sub.2 more than the median value (-0.9 mmHg) had a greater lung recruitability (19 +- 16 vs. 8 +- 6% P = 0.02), higher baseline PaCO.sub.2 (48 +- 8 vs. 41 +- 11 mmHg P = 0.07), heavier lungs (1,968 +- 829 vs. 1,521 +- 342 g P = 0.06) and more non-aerated tissue (1,009 +- 704 vs. 536 +- 188 g P = 0.02) than those who did not. Conclusions During prone position, changes in PaCO.sub.2, but not in oxygenation, are associated with lung recruitability which, in turn, is associated with the severity of lung injury. Author Affiliation: (1) Dipartimento di Anestesiologia, Terapia Intensiva e Scienze Dermatologiche, Fondazione IRCCS Ospedale Maggiore Policlinico, Mangiagalli e Regina Elena di Milano, Universita degli Studi di Milano, Via F. Sforza 35, 20122, Milan, Italy (2) Dipartimento di Radiologia, Fondazione IRCCS Ospedale Maggiore Policlinico, Mangiagalli e Regina Elena di Milano, Via F. Sforza 35, 20122, Milan, Italy (3) Zentrum fur Anaesthesiologie, Rettungs- und Intensivmedizin Georg-August-Universitat Gottingen, Robert-Koch-Str. 40, 37075, Gottingen, Germany Article History: Registration Date: 16/01/2009 Received Date: 27/08/2008 Accepted Date: 24/12/2008 Online Date: 03/02/2009

Byline: Maria Paula Caramez (1), Robert M. Kacmarek (1), Mohamed Helmy (1), Eriko Miyoshi (1), Atul Malhotra (2), Marcelo B. P. Amato (3), R. Scott Harris (4) Keywords: Lung injury; ARDS; Recruitment; Lung mechanics; Pressure--volume curve; PEEP Abstract: Purpose Many methods exist in the literature for identifying PEEP to set in ARDS patients following a lung recruitment maneuver (RM). We compared ten published parameters for setting PEEP following a RM. Methods Lung injury was induced by bilateral lung lavage in 14 female Dorset sheep, yielding a PaO.sub.2 100--150 mmHg at [F.sub.I]O.sub.2 1.0 and PEEP 5 cm[H.sub.2]O. A quasi-static P--V curve was then performed using the supersyringe method PEEP was set to 20 cm[H.sub.2]O and a RM performed with pressure control ventilation (inspiratory pressure set to 40--50 cm[H.sub.2]O), until PaO.sub.2 + PaCO.sub.2 > 400 mmHg. Following the RM, a decremental PEEP trial was performed. The PEEP was decreased in 1 cm[H.sub.2]O steps every 5 min until 15 cm[H.sub.2]O was reached. Parameters measured during the decremental PEEP trial were compared with parameters obtained from the P--V curve. Results For setting PEEP, maximum dynamic tidal respiratory compliance, maximum PaO.sub.2, maximum PaO.sub.2 + PaCO.sub.2, and minimum shunt calculated during the decremental PEEP trial, and the lower Pflex and point of maximal compliance increase on the inflation limb of the P--V curve (Pmci,i) were statistically indistinguishable. The PEEP value obtained using the deflation upper Pflex and the point of maximal compliance decrease on the deflation limb were significantly higher, and the true inflection point on the inflation limb and minimum PaCO.sub.2 were significantly lower than the other variables. Conclusion In this animal model of ARDS, dynamic tidal respiratory compliance, maximum PaO.sub.2, maximum PaO.sub.2 + PaCO.sub.2, minimum shunt, inflation lower Pflex and Pmci,i yield similar values for PEEP following a recruitment maneuver. Author Affiliation: (1) Department of Anesthesia and Critical Care, and Respiratory Care, Massachusetts General Hospital, Boston, MA, USA (2) Department of Medicine (Pulmonary, Critical Care and Sleep), Brigham and Women's Hospital, Boston, MA, USA (3) Pulmonary Department, Respiratory ICU, Hospital das Clinicas, University of Sao Paulo, Sao Paulo, Brazil (4) Department of Medicine (Pulmonary and Critical Care Unit), Massachusetts General Hospital, Boston, MA, USA Article History: Registration Date: 16/01/2009 Received Date: 19/06/2008 Accepted Date: 02/01/2009 Online Date: 31/01/2009

Byline: Enrique Piacentini (1), Marc Wysocki (2), Lluis Blanch (3) Keywords: Acute lung injury; Acute respiratory distress syndrome; Static pressure--volume curves of the respiratory system; Continuous airway positive pressure; Mathematical fitting of respiratory data Abstract: Objective To compare pressure--volume (P--V) curves obtained with the Galileo ventilator with those obtained with the CPAP method in patients with acute lung injury (ALI) or acute respiratory distress syndrome (ARDS). Design Prospective, observational study. Setting General critical care center. Patients and participants Patients with ALI/ARDS and receiving mechanical ventilation. Interventions Pressure--volume curves were obtained in random order with the CPAP technique and with the software PV Tool-2 (Galileo ventilator). Measurements and results In ten consecutive patients, airway pressure was measured by a pressure transducer and changes in lung volume were measured by respiratory inductive plethysmography. P--V curves were fitted to a sigmoidal equation with a mean R .sup.2 of 0.994 +- 0.003. Intraclass correlation coefficients were all >0.75 (P < 0.001 at all pressure levels). Lower (LIP) and upper inflection (UIP), and deflation maximum curvature (PMC) points calculated from the fitted variables showed a good correlation between methods with intraclass correlation coefficients of 0.98 (0.92, 0.99), 0.92 (0.69, 0.98), and 0.97 (0.86, 0.98), respectively (P < 0.001 in all cases). Bias and limits of agreement for LIP (0.51 +- 0.95 cm[H.sub.2]O -1.36 to 2.38 cm[H.sub.2]O), UIP (0.53 +- 1.52 cm[H.sub.2]O -2.44 to 3.50 cm[H.sub.2]O), and PMC (-0.62 +- 0.89 cm[H.sub.2]O -2.35 to 1.12 cm[H.sub.2]O) obtained with the two methods in the same patient were clinically acceptable. No adverse effects were observed. Conclusion The PV Tool-2 built into the Galileo ventilator is equivalent to the CPAP method for tracing static P--V curves of the respiratory system in critically ill patients receiving mechanical ventilation. Author Affiliation: (1) Intensive Care Unit, Hospital Mutua de Terrassa, Terrassa, Spain (2) Medical Research, Hamilton Medical AG, Bonaduz, Switzerland (3) CIBER Enfermedades Respiratorias, Critical Care Center, Hospital de Sabadell, Corporacio Parc Tauli, Institut Universitari Fundacio Parc Tauli, Universitat Autonoma de Barcelona, Parc Tauli s/n, 08208, Sabadell, Spain Article History: Registration Date: 02/10/2008 Received Date: 21/01/2008 Accepted Date: 20/09/2008 Online Date: 14/10/2008 Article note: Electronic supplementary material The online version of this article (doi: 10.1007/s00134-008-1322-2) contains supplementary material, which is available to authorized users.

Byline: Carolyn S. Calfee (1), Mark D. Eisner (2), Polly E. Parsons (3), B. Taylor Thompson (4), Edward R. Conner (1), Michael A. Matthay (5), Lorraine B. Ware (6) Keywords: Acute respiratory distress syndrome; Acute lung injury; Intracellular adhesion molecule-1; Pulmonary edema Abstract: Objective To determine if levels of soluble intercellular adhesion molecule-1 (sICAM-1), a marker of alveolar epithelial and endothelial injury, differ in patients with hydrostatic pulmonary edema and acute lung injury (ALI) and are associated with clinical outcomes in patients with ALI. Design, setting, and participants Measurement of sICAM-1 levels in (1) plasma and edema fluid from 67 patients with either hydrostatic pulmonary edema or ALI enrolled in an observational, prospective single center study, and (2) in plasma from 778 patients with ALI enrolled in a large multi-center randomized controlled trial of ventilator strategy. Results In the single-center study, levels of sICAM-1 were significantly higher in both edema fluid and plasma (median 938 and 545 ng/ml, respectively) from ALI patients compared to hydrostatic edema patients (median 384 and 177 ng/ml, P < 0.03 for both comparisons). In the multi-center study, higher plasma sICAM-1 levels were associated with poor clinical outcomes in both unadjusted and multivariable models. Subjects with ALI whose plasma sICAM-1 levels increased over the first 3 days of the study had a higher risk of death, after adjusting for other important predictors of outcome (odds ratio 1.48 95% CI 1.03--2.12, P = 0.03). Conclusions Both plasma and edema fluid levels of sICAM-1 are higher in patients with ALI than in patients with hydrostatic pulmonary edema. Higher plasma sICAM-1 levels and increasing sICAM-1 levels over time are associated with poor clinical outcomes in ALI. Measurement of sICAM-1 levels may be useful for identifying patients at highest risk of poor outcomes from ALI. Author Affiliation: (1) Division of Pulmonary and Critical Care Medicine, Department of Medicine, University of California, San Francisco, 505 Parnassus Avenue, San Francisco, CA, 94143-0111, USA (2) Divisions of Pulmonary and Critical Care Medicine and Occupational and Environmental Medicine, Department of Medicine, University of California, San Francisco, San Francisco, CA, USA (3) Division of Pulmonary and Critical Care Medicine, Department of Medicine, Fletcher Allen Health Care, University of Vermont, Burlington, VT, USA (4) Pulmonary/Critical Care Unit, Department of Medicine, Massachusetts General Hospital, Boston, MA, USA (5) Cardiovascular Research Institute, Departments of Medicine and Anesthesia, University of California, San Francisco, CA, USA (6) Division of Allergy, Pulmonary and Critical Care Medicine, Department of Medicine, Vanderbilt University School of Medicine, Nashville, TN, USA Article History: Registration Date: 16/07/2008 Received Date: 09/01/2008 Accepted Date: 09/07/2008 Online Date: 01/08/2008 Article note: The members of the NHLBI ARDS Clinical Trials Network are listed in the Appendix.

Byline: Wen-Liang Yu (1), Zhu-Jin Lu (1), Ying Wang (2), Li-Ping Shi (3), Feng-Wu Kuang (4), Su-Yun Qian (5), Qi-Yi Zeng (6), Min-Hui Xie (7), Guo-Ying Zhang (8), De-Yi Zhuang (9), Xun-Mei Fan (5), Bo Sun (1) Keywords: Acute respiratory distress syndrome; Epidemiology; Intensive care; Mortality; Respiratory therapy Abstract: Objective To assess the incidence of, predisposing factors for, and the rates and relative risks of mortality from acute respiratory distress syndrome (ARDS) in pediatric patients. Design A prospective study in 12 consecutive months from 2004 to 2005 in 25 pediatric intensive care units (PICUs). Patients and setting ARDS was diagnosed according to the 1994 American--European Consensus Conference definitions, applied to all severely ill admissions between 1 month and 14 years of age. The PICUs were in major municipalities and provincial cities, and half were university affiliated. Measurements and results From a total of 12,018 admissions, 7,269 were severely ill. One hundred and five (1.44%) patients developed ARDS and 64 (61.0%) died, which accounts for 13.2%, of the total ICU death (n = 485, 6.7%) or a nine times relative risk of dying. The median age at onset of ARDS was 24 months and 40% were less than 12 month old. Median time from PICU admission to the onset of ARDS was 16 h, and in 63% Conclusions ARDS has a high mortality in these Chinese PICUs, especially in those with pneumonia and sepsis, and adequate management including lung protective ventilation strategy is required. Author Affiliation: (1) Children's Hospital of Fudan University, 183 Feng Lin Road, 200032, Shanghai, People's Republic of China (2) Shanghai Children's Medical Center of Shanghai Jiaotong University, Shanghai, People's Republic of China (3) Children's Hospital of Zhejiang University, Zhejiang, People's Republic of China (4) Children's Hospital of Chongqing Medical University, Chongqing, People's Republic of China (5) Beijing Children's Hospital of Capital University of Medical Sciences, Beijing, People's Republic of China (6) Guangzhou Children's Hospital, Guangdong, People's Republic of China (7) Children's Hospital of Suzhou University, Jiangsu, People's Republic of China (8) Chengdu Children's Hospital, Sichuan, People's Republic of China (9) Quanzhou Children's Hospital, Fujian, People's Republic of China Article History: Registration Date: 26/08/2008 Received Date: 20/07/2006 Accepted Date: 29/04/2008 Online Date: 30/09/2008 Article note: Electronic supplementary material The online version of this article (doi: 10.1007/s00134-008-1254-x) contains supplementary material, which is available to authorized users.

The article discusses the causes, symptoms, diagnosis and treatment methodologies for acute pulmonary embolism. A case study of a 62-year-old man with worsening dyspnea is highlighted to better understand treatment and management methodologies.

Byline: Alysson R. Carvalho (1,2), Peter M. Spieth (1), Paolo Pelosi (3), Marcos F. Vidal Melo (4), Thea Koch (1), Frederico C. Jandre (2), Antonio Giannella-Neto (2), Marcelo Gama Abreu (1,5) Keywords: Acute lung injury; Lung protective strategy; Ventilator-induced lung injury Abstract: Objective To evaluate the ability of three indices derived from the airway pressure curve for titrating positive end-expiratory pressure (PEEP) to minimize mechanical stress while improving lung aeration assessed by computed tomography (CT). Design Prospective, experimental study. Setting University research facilities. Subjects Twelve pigs. Interventions Animals were anesthetized and mechanically ventilated with tidal volume of 7 ml kg.sup.-1. In non-injured lungs (n = 6), PEEP was set at 16 cm[H.sub.2]O and stepwise decreased until zero. Acute lung injury was then induced either with oleic acid (n = 6) or surfactant depletion (n = 6). A recruitment maneuver was performed, the PEEP set at 26 cm[H.sub.2]O and decreased stepwise until zero. CT scans were obtained at end-expiratory and end-inspiratory pauses. The elastance of the respiratory system (Ers), the stress index and the percentage of volume-dependent elastance (%E .sub.2) were estimated. Measurements and main results In non-injured and injured lungs, the PEEP at which Ers was lowest (8--4 and 16--12 cm[H.sub.2]O, respectively) corresponded to the best compromise between recruitment/hyperinflation. In non-injured lungs, stress index and %E .sub.2 correlated with tidal recruitment and hyperinflation. In injured lungs, stress index and %E .sub.2 suggested overdistension at all PEEP levels, whereas the CT scans evidenced tidal recruitment and hyperinflation simultaneously. Conclusion During ventilation with low tidal volumes, Ers seems to be useful for guiding PEEP titration in non-injured and injured lungs, while stress index and %E .sub.2 are useful in non-injured lungs only. Our results suggest that Ers can be superior to the stress index and %E .sub.2 to guide PEEP titration in focal loss of lung aeration. Author Affiliation: (1) Clinic of Anesthesiology and Intensive Care Therapy, Medical Faculty, University Hospital Carl Gustav Carus, Dresden, Germany (2) Program of Biomedical Engineering, COPPE, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil (3) Department of Ambient, Health and Safety, University of Insubria, Varese, Italy (4) Department of Anesthesia and Critical Care, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA (5) Pulmonary Engineering Group, Department of Anesthesiology and Intensive Care Therapy, University Hospital Dresden, Fetscherstrasse 74, 01307, Dresden, Germany Article History: Registration Date: 18/09/2008 Received Date: 15/10/2007 Accepted Date: 08/09/2008 Online Date: 30/09/2008 Article note: Electronic supplementary material The online version of this article (doi: 10.1007/s00134-008-1301-7) contains supplementary material, which is available to authorized users.

Byline: R. S. Rodrigues (1), P. R. Miller (2), F. A. Bozza (3), E. Marchiori (1,4), G. A. Zimmerman (5), J. M. Hoffman (6), K. A. Morton (7,8) Keywords: Acute respiratory distress syndrome; Adult respiratory distress syndrome; Postitron emission tomography; Fluordeoxyglucose; Acute lung injury Abstract: Objective To compare the pattern of lung uptake of 18F-fluorodeoxyglucose (FDG) by positron emission tomography (PET) imaging in patients with lung contusion that developed or did not progress to acute respiratory distress syndrome (ARDS). Design Prospective, observational study. Setting Trauma Center (academic urban hospital). Patients and interventions Eight patients with blunt thoracic trauma and pulmonary contusion, confirmed by computed tomography (CT) on admission, underwent repeat CT and FDG-PET (on the same day) 24--72 h after admission. Results No subjects met the criteria for ARDS at the time of the PET and second CT. Four subjects subsequently developed ARDS 1--3 days after the PET scan the other four did not develop the syndrome. Three of the four subjects who subsequently developed ARDS showed diffuse FDG uptake throughout the entire lungs, while those who did not develop ARDS showed significant FDG uptake only in areas of focal lung opacity (non or poorly aerated lung units) on CT. FDG uptake in normally aerated lung regions was higher for those who subsequently developed ARDS than those who did not, approaching statistical significance. The normally aerated tissue:liver ratio was significantly higher in subjects who developed ARDS than in those who did not (P = 0.029). Conclusion In this small series of patients with thoracic trauma, diffuse lung uptake of FDG was detected by PET imaging 1--3 days prior to clinically determined ARDS. Author Affiliation: (1) Department of Radiology, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil (2) Department of Surgery, Wake Forest University, Winston-Salem, NC, USA (3) IPEC, Fundacao Oswaldo Cruz, Rio de Janeiro, Rio de Janeiro, Brazil (4) Department of Radiology, Federal University of Fluminense, Rio de Janeiro, Brazil (5) Department of Internal Medicine and Program in Human Molecular Biology and Genetics, University of Utah, Salt Lake City, UT, USA (6) Huntsman Cancer Institute, University of Utah, Salt Lake City, UT, USA (7) Department of Radiology, University of Utah, Salt Lake City, UT, USA (8) University of Utah Hospitals and Clinics, 30 North 1900 East. Room 1A71, Salt Lake City, UT, 84132-2140, USA Article History: Registration Date: 09/07/2008 Received Date: 03/12/2007 Accepted Date: 07/07/2008 Online Date: 06/08/2008 Article note: Electronic supplementary material The online version of this article (doi: 10.1007/s00134-008-1220-7) contains supplementary material, which is available to authorized users.

Byline: Benjamin Maddison (1), Riccardo Giudici (2), Enrico Calzia (3), Christopher Wolff (1), Charles Hinds (1), Peter Radermacher (3), Rupert M. Pearse (1) Keywords: Cardiovascular monitoring; Intrathoracic blood volume; Extravascular lung water; Lithium indicator dilution; Gravimetry; Acute lung injury Abstract: Objective To compare the lithium-thermal double indicator dilution (Li-thermal), indocyanine green-thermal double indicator dilution (ICG-thermal), single thermal indicator dilution (single-thermal) and gravimetric techniques of extravascular lung water volume (EVLW) measurement in porcine models of acute lung injury. Design Two animal models designed to invoke a systemic inflammatory response. Setting Laboratory study. Subjects A total of 12 immature Deutsches Landschwein pigs. Interventions Extravascular lung water volume was measured at four time points using Li-thermal, ICG-thermal and single-thermal techniques. Measurements were performed using existing technology according to manufacturer's instructions. Post-mortem gravimetric EVLW measurements were performed by measuring wet and dry mass of lung tissue. Measurements were compared using the Bland--Altman method. Data are presented as mean (SD). Measurements and main results Data were collected in 12 animals and comparison between all 4 techniques was possible in 10 animals. EVLW measured by gravimetry was 9.2 (+-3.0)ml kg.sup.-1. When compared to gravimetry, both Li-thermal and ICG-thermal techniques showed minimal bias but wide limits of agreement (LOA) [Li-thermal: bias -1.8 ml kg.sup.-1 (LOA +- 13.1) ICG-thermal bias -1.0 ml kg.sup.-1 (LOA +- 6.6)]. Comparison between the single-thermal and gravimetric methods identified both considerable bias and wide LOA [+8.5 ml kg.sup.-1 (LOA +- 14.5)]. Conclusion Clinically significant differences between EVLW measurements obtained with the gravimetric method and three in vivo indicator dilution techniques were identified. While none of the techniques could be considered ideal, the ICG-thermal method appeared more reliable than either the Li-thermal or single thermal techniques. Further research is required to determine whether the accuracy of the prototype Li-thermal technique can be improved. Author Affiliation: (1) Intensive Care Unit, Royal London Hospital, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, Whitechapel, London, E1 1BB, UK (2) Institute of Anaesthesiology and Intensive Care Medicine, Polo Universitario San Paolo, University of Milan, Milan, Italy (3) Sektion Anasthesiologische Pathophysiologie und Verfahrensentwicklung, Universitatsklinikum, Ulm, Germany Article History: Registration Date: 24/06/2008 Received Date: 12/03/2008 Accepted Date: 12/06/2008 Online Date: 08/07/2008 Article note: Electronic supplementary material The online version of this article (doi: 10.1007/s00134-008-1207-4) contains supplementary material, which is available to authorized users.

Thoracic electrical impedance tomography (EIT) seems to be particularly useful for the monitoring of patients suffering from the acute respiratory distress syndrome (ARDS), because it is capable of detecting dynamic shifts of body fluids and lung aeration right at the bedside. EIT-derived numeric parameters would help the physician to evaluate the state of the lung more objectively. Therefore, we created a finite element method (FEM)-model of a human thorax and tested new ventilation indices regarding their ability to quantitatively describe structural changes in the lung due to the gravitationally dependent lung collapse. Additionally, we examined which current-injection electrode pair is best suited for the separation of lung and heart activity. Index Terms--Acute respiratory distress syndrome (ARDS), electrical impedance tomography (EIT), finite element method (FEM) thorax model, fluid shifts, ventilation indices.

Byline: Fekri Abroug (1), Lamia Ouanes-Besbes (1), Souheil Elatrous (2), Laurent Brochard (3) Keywords: ARDS; ALI; Mechanical ventilation; Prone positioning Abstract: Objective To compare the effects of ventilation in prone and in supine position in patients with acute lung injury/acute respiratory distress syndrome (ALI/ARDS). Design Meta-analysis of randomised controlled trials. Data sources BioMedCentral, PubMed, CINAHL, and Embase (to November 2007), with additional information from authors. Measurements and results From selected randomised controlled trials comparing positioning in ALI/ARDS we extracted data concerning study design, disease severity, clinical outcomes, and adverse events. Five trials including 1,372 patients met the inclusion criteria for mortality analysis one trial was added to assess the effects on acquisition of ventilator-associated pneumonia (VAP). The included trials were significantly underpowered and enrolled patients with varying severity. Prone positioning duration and mechanical ventilation strategy were not standardised across studies. Using a fixed-effects model, we did not find a significant effect of prone positioning (proning) on mortality (odds ratio 0.97, 95% confidence interval 0.77--1.22). The PaO.sub.2/FiO.sub.2 ratio increased significantly more with proning (weighted means difference 25 mmHg, pa- Conclusions Prone position is not associated with a significant reduction in mortality from ALI/ARDS despite a significant increase in PaO.sub.2/FiO.sub.2, is safe, and tends to decrease VAP. Published studies exhibit substantial clinical heterogeneity, suggesting that an adequately sized study optimising the duration of proning and ventilation strategy is warranted to enable definitive conclusions to be drawn. Author Affiliation: (1) Service de Reanimation Polyvalente, CHU F. Bourguiba, 5000, Monastir, Tunisia (2) Service de Reanimation Medicale, CHU T. Sfar, Mahdia, Tunisia (3) Service de Reanimation Medicale, AP-HP, Hopital Henri Mondor, INSERM U 841, Creteil, France Article History: Registration Date: 28/02/2008 Received Date: 02/08/2007 Accepted Date: 05/01/2008 Online Date: 19/03/2008

Byline: Martin C. J. Kneyber (1), Arno G. A. Brouwers (1), Jochem A. Caris (1), Sunita Chedamni (1), Frans B. Plotz (1) Keywords: Acute respiratory distress syndrome; Mechanically ventilated; Pediatric intensive care unit; The Netherlands; Underdiagnoses Abstract: Objective To describe the incidence of acute respiratory distress syndrome (ARDS) in mechanically ventilated children and to study whether ARDS is underrecognized in this patient population. Design and setting Retrospective observational study in a single-center bed pediatric intensive care unit serving two Dutch provinces. Patients 533 mechanically ventilated children aged 0--16 years, all of whom met the North-American European Consensus Conference criteria for ARDS. Measurements and results Chest radiographs were screened for the novel presence of bilateral infiltrates, in patients with bilateral infiltrates the PaO.sub.2/FIO.sub.2 ratio was calculated on two separate consecutive measurements. If below 200, the patient was classified as having ARDS. Left ventricular dysfunction was ruled out by echocardiography. The incidence was calculated by obtaining the number of children aged 0--16 years in our region. For each patient it was noted whether the patient was currently considered to have ARDS. Forty-one patients (7.7%) met the criteria for ARDS, with an incidence of 2.2 per 100,000 per year. The mortality rate was 20.4%. Thirty patients (73.1%) had primary ARDS, mainly from viral lower respiratory tract disease. Only ten patients (24.4%) currently had ARDS. Conclusions The incidence of pediatric ARDS is low compared to that of adult ARDS, and further underestimated as most patients were diagnosed by their underlying diseases. Author Affiliation: (1) Department of Pediatric Intensive Care, V.U. University Medical Center, P.O. Box 7057, 1007 MB, Amsterdam, The Netherlands Article History: Registration Date: 25/01/2008 Received Date: 27/04/2007 Accepted Date: 21/01/2008 Online Date: 21/02/2008

Byline: Torsten Meier (1), Henning Luepschen (3), Jan Karsten (1), Thorsten Leibecke (2), Martin Grossherr (1), Hartmut Gehring (1), Steffen Leonhardt (3) Keywords: Electrical impedance tomography; Computed tomography; Acute lung injury; Lung recruitment; Positive end-expiratory pressure Abstract: Objective To investigate whether electrical impedance tomography (EIT) is capable of monitoring regional lung recruitment and lung collapse during a positive end-expiratory pressure (PEEP) trial. Design Experimental animal study of acute lung injury. Subject Six pigs with saline-lavage-induced acute lung injury. Interventions An incremental and decremental PEEP trial at ten pressure levels was performed. Ventilatory, gas exchange, and hemodynamic parameters were automatically recorded. EIT and computed tomography (CT) scans of the same slice were simultaneously taken at each PEEP level. Measurements and results A significant correlation between EIT and CT analyses of end-expiratory gas volumes (ra-=a-0.98 up to 0.99) and tidal volumes (ra-=a-0.55 up to ra-=a-0.88) could be demonstrated. Changes in global and regional tidal volumes and arterial oxygenation (PaO.sub.2/FiO.sub.2) demonstrated recruitment/derecruitment during the trial, but at different onsets. During the decremental trial, derecruitment first occurred in dependent lung areas. This was indicated by lowered regional tidal volumes measured in this area and by a decrease of PaO.sub.2/FiO.sub.2. At the same time, the global tidal volume still continued to increase, because the increase of ventilation of the non-dependent areas was higher than the loss in the dependent areas. This indicates that opposing regional changes might cancel each other out when combined in a global parameter. Conclusions EIT is suitable for monitoring the dynamic effects of PEEP variations on the regional change of tidal volume. It is superior to global ventilation parameters in assessing the beginning of alveolar recruitment and lung collapse. Author Affiliation: (1) Department of Anesthesiology, University Medical Center Schleswig-Holstein, Campus Lubeck, Ratzeburger Allee 160, 23538, Lubeck, Germany (2) Department of Radiology, University Medical Center Schleswig-Holstein, Lubeck, Germany (3) Helmholtz Institute for Biomedical Engineering, RWTH Aachen University, Aachen, Germany Article History: Registration Date: 29/06/2007 Received Date: 10/11/2006 Accepted Date: 28/06/2007 Online Date: 25/07/2007

Byline: Jesus Villar (1,2,3), Carlos Flores (2,4,5), Lina Perez-Mendez (2,6), Nicole Maca-Meyer (4), Elena Espinosa (7), Jesus Blanco (2,8), Ruben Sanguesa (7), Arturo Muriel (8), Paula Tejera (4), Mercedes Muros (2,9), Arthur S. Slutsky (3,10) Keywords: Association study; Genetic susceptibility; Genetic variation; Human sepsis Abstract: Objective The insertion/deletion (I/D) of a 289 base pair Alu repeat sequence polymorphism in the angiotensin-converting enzyme gene (ACE) has been shown to predict susceptibility and outcome in the acute respiratory distress syndrome (ARDS). We hypothesized that the I/D polymorphism also confers susceptibility to sepsis and is a predisposing factor for morbidity and mortality of patients with severe sepsis. Design and setting Case-control study including 212 consecutive patients fulfilling criteria for severe sepsis admitted to a Spanish network of postsurgical and critical care units, and 364 population-based controls. Susceptibility to severe sepsis was evaluated as primary outcome mortality in severe sepsis, susceptibility to sepsis-induced ARDS, and mortality in sepsis-induced ARDS were examined as secondary outcomes. An additive model of inheritance in which patients were classified into three genotype groups (II, ID, and DD) was used for association testing. Measurements and results Genotype and allele frequencies of I/D were distributed similarly in all septic, ARDS, and non-ARDS patients and in population-based controls. ACE I/D polymorphism was not associated with severe sepsis susceptibility or mortality. The ACE I/D polymorphism was associated neither with sepsis-induced ARDS susceptibility (pa-=a-0.895) or mortality (pa-=a-0.950). These results remained nonsignificant when adjusted for other covariates using multiple logistic regression analysis or Kaplan--Meier estimates of 28-day survival. Conclusions Our data do not support an association of the ACE gene I/D polymorphism with susceptibility or mortality in severe sepsis or with sepsis-induced ARDS in Spanish patients. Author Affiliation: (1) Multidisciplinary Organ Dysfunction Evaluation Research Network (MODERN), Research Unit, Hospital Universitario Dr. Negrin, Barranco de la Ballena, s/n - 4th floor, south wing, 35010, Las Palmas de Gran Canaria, Canary Islands, Spain (2) Instituto de Salud Carlos III, CIBER de Enfermedades Respiratorias, Madrid, Spain (3) Keenan Research Center, St. Michael's Hospital, Toronto, Ontario, Canada (4) Division of Human Genetics, Research Unit, Hospital Universitario NS de Candelaria, Tenerife, Spain (5) Department of Medicine, Division of Pulmonary and Critical Care, University of Chicago, Chicago, Ill, USA (6) Division of Clinical and Genetic Epidemiology, Research Unit, Hospital Universitario NS de Candelaria, Tenerife, Spain (7) Department of Anesthesia, Hospital Universitario NS de Candelaria, Tenerife, Spain (8) Intensive Care Unit, Hospital Universitario Rio Hortega, Valladolid, Spain (9) Department of Clinical Biochemistry, Hospital Universitario NS de Candelaria, Tenerife, Spain (10) Department of Medicine, Interdepartmental Division of Critical Care Medicine, University of Toronto, Toronto, Ontario, Canada Article History: Registration Date: 06/11/2007 Received Date: 28/05/2007 Accepted Date: 17/09/2007 Online Date: 05/12/2007 Article note: This research was supported by grants from FUNCIS (53/04) and the Ministerio de Educacion y Ciencia, Spain (SAF2004-06833). J.V. is the principal investigator in both grants. The authors named above wrote this article on behalf of the GRECIA and GEN-SEP groups. The members of the GRECIA and GEN-SEP groups are listed under Acknowledgements at the end of the article. J. Villar, C. Flores, and L. Perez-Mendez contributed equally to this work. Electronic supplementary material The online version of this article (doi: 10.1007/s00134-007-0937-z) contains supplementary material, which is available to authorized users.

Desmosine is a stable breakdown product of elastin that can be reliably measured in urine samples. We tested the hypothesis that higher baseline urine desmosine would be associated with higher mortality in 579 of 861 patients included in the recent Acute Respiratory Distress Syndrome Network trial of lower tidal volume ventilation (1). We also correlated urine desmosine levels with indexes of disease severity. Finally, we assessed whether urine desmosine was lower in patients who received lower tidal volumes. Desmosine was measured by radioimmunoassay in urine samples from days 0, 1, and 3 of the study. The data were expressed as a ratio of urine desmosine to urine creatinine to control for renal dilution. The results show that higher baseline (day 0) urine desmosine-to-creatinine concentration was associated with a higher risk of death on adjusted analysis (odds ratio 1.36, 95% confidence interval 1.02-1.82, P = 0.03). Urine desmosine increased in both ventilator groups from day 0 to day 3, but the average rise was higher in the 12-ml/kg predicted body weight group compared with the 6-ml/kg predicted body weight group (P = 0.053, repeated-measures model). In conclusion, patients with acute lung injury ventilated with lower tidal volumes have lower urine desmosine levels, a finding that may reflect reduced extracellular matrix breakdown. These results illustrate the value of evaluating urinary biological markers that may have prognostic and pathogenetic significance in acute lung injury. acute respiratory distress syndrome; extracellular matrix; stretch injury

OBJECTIVES. It is well known that children attending childcare have a higher risk of acute respiratory infections compared with children in home care; however, knowledge is sparse regarding how the excess risk of acute respiratory infection varies with age, time since enrollment, and other factors. METHODS. A national register-based study of 138 821 inpatient admissions to hospital for acute respiratory infection during 3 982 925 person-years of follow-up in Danish children aged 0 to 5 years. Data on child and family characteristics, childcare attendance, and hospitalizations were obtained from Danish registries. The outcome of the study was inpatient admissions to hospital for acute respiratory infection. Incidence rate ratios were estimated using Poisson regression. RESULTS. In children CONCLUSIONS. The increased risk of acute respiratory infection was most pronounced among 0- to 2-year-old children living with no other children during the first 6 months of enrollment. Our findings may suggest that it would be optimal to postpone enrollment into childcare until after 1 year of age. Key Words childcare, acute respiratory infection, morbidity, epidemiology Abbreviations ARI--acute respiratory infection DCRS--Danish Civil Registration System DNPR--Danish National Patient Registry ICD--International Classification of Diseases URI--upper respiratory infection LRI--lower respiratory infection IRR--incidence rate ratio CI--confidence interval, PREVIOUS STUDIES HAVE consistently found that children who are taken care of in a childcare facility away from their home have a higher risk of acute respiratory infections (ARIs) than [...]

A study was conducted to examine the relationship between the percentage of potentially recruitable lung, in the acute respiratory distress syndrome (ARDS) as indicated by computed tomography (CT) and effects of positive end-expiratory pressure (PEEP). In ARDS, the percentage of potentially recruitable lung is extremely variable and is strongly associated with the response to PEEP.

The biologic actions of inhaled nitric oxide are reviewed, clinical indications for its administration in adults is discussed and possible future developments are assessed. Inhaled nitric oxide is a selective pulmonary vasodilator that improves ventilation-perfusion matching at low doses in patients with acute respiratory failure, potentially improving oxygenation and lowering pulmonary vascular resistance.

A systematic English-language literature search of MEDLINE is conducted to identify reports of invasive ventilatory and adjunctive therapies in adult patients with acute lung injury and acute respiratory distress syndrome. Results reveal that volume- and pressure-limited ventilation strategies should be used in managing adult acute lung injury and acute respiratory distress syndrome patients.

Re-expansion of a collapsed lung increases the microvascular permeability and causes reexpansion pulmonary edema. Neutrophils and their products have been implicated in the development of this phenomenon. The small GTP-binding proteins Rho and its target Rho-kinase (ROCK) regulate endothelial permeability, although their roles in reexpansion pulmonary edema remain unclear. We studied the contribution of ROCK to pulmonary endothelial and epithelial permeability in a rabbit model of this disorder. Endothelial and epithelial permeability was assessed by measuring the tissue-to-plasma (T/P) and bronchoalveolar lavage (BAL) fluid-to-plasma (B/P) ratios with [sup.125I]-1abeled albumin. After intratracheal instillation of [sup.125I]-albumin, epithelial permeability was also assessed from the plasma leak (PL) index, the ratio of [sup.125I]-albumin in plasma/total amount of instilled [sup.125I]-albumin. T/P, B/P, and PL index were significantly increased in the reexpanded lung. These increases were attenuated by pretreatment with Y-27632, a specific ROCK inhibitor. However, neutrophil influx, neutrophil elastase activity, and malondialdehyde concentrations in BAL fluid collected from the reexpanded lung were not changed by Y-27632. In endothelial monolayers, Y-27632 significantly attenuated the [H.sub.2][O.sub.2]-induced increase in permeability and mitigated the morphological changes in the actin microfilament cytoskeleton of endothelial cells. These in vivo and in vitro observations suggest that the Rho/ ROCK pathway contributes to the increase in alveolar barrier permeability associated with reexpansion pulmonary edema. acute lung injury; acute respiratory distress syndrome; re-expansion pulmonary edema; Rho; Rho-kinase

A case study of a 22-year-old woman, suffering from low back and leg pain who was diagnosed with sick cell anemia at six years of age, is presented. The woman had fallen backwards while ice-skating, six days before she was admitted in the hospital and was declared dead 23 hours later.

Abstract. The lung is frequently the first failing organ during the sequential development of multiple organ dysfunction under both septic or non-septic conditions. The present study compared polymorphisms of tumor [...]

A case of a 67-year-old man who was transferred to the Massachusetts General Hospital with acute respiratory failure is described. With antibiotic therapy and respiratory support, his symptoms rapidly improved over 48 hours.

Byline: Dick G. Markhorst (1,3), Huibert R. Genderingen (2), Adrianus J. Vught (3) Keywords: Theoretical models; Respiratory mechanics; Positive-pressure; Tidal volume; Pulmonary alveoli Abstract: Objective To study the value of objective pressure-volume characteristics for predicting optimal airway pressures and the development of atelectasis and overstretching during a structured lung volume recruitment procedure with subsequent reduction in airway pressures. Methods We used a mathematical model of a lung with adjustable characteristics of acute respiratory distress syndrome (ARDS) characteristics. Simulations were performed in five grades of ARDS in the presence of pure alveolar or combined alveolar-small airway closure as well complete or incomplete lung volume recruitability. For each simulation optimal end-expiratory pressure was determined. A static pressure-volume curve was constructed and objective characteristics of this curve calculated. The predictive value of these characteristics for end-expiratory atelectasis, overstretching, and optimal end-expiratory pressure was assessed. Results Simultaneous alveolar recruitment and overstretching during inflation were more pronounced than alveolar derecruitment and overstretching during deflation. End-expiratory pressure needed to prevent significant alveolar collapse in severe ARDS resulted in maximal safe tidal volumes that may be insufficient for adequate ventilation using conventional mechanical ventilatory modes. Plateau pressures well below the 'upper corner point' (airway pressure where compliance decreases) resulted in significant alveolar overstretching. Conclusions A recruitment maneuver followed by subsequent reduction in airway pressure limits end-expiratory atelectasis, overstretching, and pressure. None of the objective characteristics of the pressure-volume curve was predictive for end-expiratory atelectasis, overstretching, or optimal airway pressure. Author Affiliation: (1) Pediatric Intensive Care Unit, Vrije Universiteit Medical Center, P.O. Box 7057, 1007 MB, Amsterdam, The Netherlands (2) Department of Physics and Medical Technology, Vrije Universiteit Medical Center, Amsterdam, The Netherlands (3) Pediatric Intensive Care Unit, University Medical Center Utrecht, Utrecht, The Netherlands Article History: Registration Date: 26/08/2004 Received Date: 13/05/2003 Accepted Date: 25/08/2004 Online Date: 15/09/2004 Article note: Electronic Supplementary Material Supplementary material is available for this article if you access the article at http://dx.doi.org/10.1007/s00134-004-2446-7. A link in the frame on the left on that page takes you directly to the supplementary material.

Byline: Frederique Bayle (1), Claude Guerin (1,2), Jean-Paul Viale (2,3), Jean-Christophe Richard (1,2), Guy Annat (2,4) Keywords: Acute respiratory distress syndrome; Oleic acid; Sigmoid equation; Volume Pressure curves; Positive end-expiratory pressure Abstract: Objectives To describe inflation and deflation volume-pressure (V-P) curves of the respiratory system by the sigmoidal equation at different levels of positive end-expiratory pressure (PEEP) in acute lung injury. Design Experimental study. Setting Physiological laboratory in a university setting. Subjects Six pigs of 25 kg each. Interventions Acute lung injury was induced by oleic acid. PEEP was applied from 0 to 15 cm[H.sub.2]O and from 15 to 0 cm[H.sub.2]O for 10 min in steps of 5 cm[H.sub.2]O. Measurements and results Inflation and deflation V-P curves were constructed from an automated super-syringe that delivers a constant flow of 7 l/min in both inspiratory and expiratory directions. V-P curves were obtained at each level of PEEP without disconnecting the animal from the ventilator. The experimental data were fitted to the sigmoid equation which provided the true inflection point (c), the point of maximal compliance increase (Pmci) reflecting opening/closure and the point of maximal compliance decrease (Pmcd) reflecting end of recruitment/onset of de-recruitment. The sigmoid equation provided an excellent fit. The values of the coefficients of determination were greater than 0.970 (median 0.996, IQR 0.994--0.997 for the 84 determinations). Negative values of Pmci in the deflation limb of the V-P curve were recorded in five pigs, suggesting closure below the volume range studied. Conclusions Inflation and deflation V-P curves at different PEEPs can be fitted by the sigmoid equation. However, further work is needed to investigate the meaning of negative values for Pmci. Author Affiliation: (1) Service de Reanimation Medicale et d'Assistance Respiratoire, Hopital de la Croix-Rousse, 103 Grande Rue de la Croix-Rousse, 69004, Lyon, France (2) Equipe d'accueil EA 1896, Universite Claude Bernard Lyon I, 69008, Lyon, France (3) Departement d'Anesthesie Reanimation, Hopital de la Croix-Rousse, 103 Grande Rue de la Croix-Rousse, 69004, Lyon, France (4) Laboratoire de Physiologie, Faculte de Medecine Grange Blanche, Universite Claude Bernard Lyon I, 69008, Lyon, France Article History: Registration Date: 03/08/2004 Received Date: 02/11/2003 Accepted Date: 27/07/2004 Online Date: 10/09/2004

Byline: Michael A. Pakulla (1), David Seidel (1), Detlef Obal (1), Stephan A. Loer (1) Keywords: Rats; Acid aspiration; Partial liquid ventilation Abstract: Objective Partial liquid ventilation can improve respiratory functions in acid-induced lung injury. We studied the effects of the interval between induction of injury and initiation of partial liquid ventilation on survival, gas exchange, and pulmonary neutrophil accumulation. Material and methods Anesthetized rats were randomly assigned to one of five groups (n = 6 per group). Group 1 served as the control group, in the other groups an extended lung injury was induced by intratracheal instillation of hydrochloric acid. Whereas lungs of group 2 were gas-ventilated, group 3 received an early partial liquid ventilation (5 min after acid instillation) and group 4 a delayed partial liquid ventilation (30 min after acid instillation, 5 ml/kg perfluorocarbon). Group 5 received an additional continuous perfluorocarbon application of 5 ml*kg.sup.-1*h.sup.-1 (30 min after acid instillation). Blood gases were measured with an intravascular blood gas sensor. Results Acid instillation resulted in a marked decrease in PO.sub.2-values within 30 min (from 481+-37 mmHg to 128+-71 mmHg, FiO.sub.2 1.0). Survival rate of the study period (12 h) was higher with early partial liquid ventilation. We observed no differences between groups in peak PO.sub.2-values during treatment. Histopathological examination, however, showed less pulmonary neutrophil accumulation in lungs of the early partial liquid ventilation group when compared to the delayed partial liquid ventilation group. Conclusions Our results suggest that early partial liquid ventilation increases survival after extended acid-induced lung injury. While effects on arterial oxygenation appear not to predict acute survival we observed less intrapulmonary neutrophil accumulation with early partial liquid ventilation. Author Affiliation: (1) Department of Anesthesiology, Heinrich-Heine-University, Moorenstrasse 5, 40225, Dusseldorf, Germany Article History: Registration Date: 03/08/2004 Received Date: 16/12/2003 Accepted Date: 26/07/2004 Online Date: 21/09/2004 Article note: Supported by a grant to S. A. Loer from the research committee of the medical faculty of the University of Dusseldorf

Byline: Sun Jong Kim (1), Bum Jin Oh (2), Jin Sung Lee (3), Chae-Man Lim (1), Tae Sun Shim (1), Sang Do Lee (1), Woo Sung Kim (1), Dong Soon Kim (1), Won Dong Kim (1), Younsuck Koh (1) Keywords: Acute respiratory distress syndrome; Pulmonary; Extrapulmonary; Long-term outcome Abstract: Objective To determine whether long-term outcome differs between acute respiratory distress syndrome (ARDS) resulting from pulmonary (ARDSp) and extrapulmonary (ARDSexp) causes. Design Observational study. Setting Medical intensive care unit of a university hospital. Patients Twenty-nine ARDS patients (16 ARDSp and 13 ARDSexp) who survived over 6 months after diagnosis. Measurements and results The two groups did not differ according to demographic data and severity indices on admission. The duration of ICU stay (median 21 days [interquartile range, 12--43 days] vs 12 [6.5--20] days, p=0.097) tended to be longer and total ventilation time (360 [96--700] h vs 144 [42.5--216] h, p=0.045) were longer in the patients with ARDSp. The ARDSp patients showed more severe abnormalities on thin-section computed tomography (CT), including ground-glass opacity (GGO 6 [3--16] vs 0 [0--2.5], p=0.002), reticular density (12 [8--14] vs 5 [2--9], p=0.033) and the sum of all four patterns of lesion (20 [11--27] vs 5 [2--12], p=0.006). There were no between-group differences in Spitzer's Quality of Life index and the Chronic Respiratory Questionnaire. Conclusions These results suggest that ARDSp would leave more severe lung sequelae than ARDSexp, but the clinical relevance of their difference is questionable. Author Affiliation: (1) Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, , Asan Medical Center, University of Ulsan College of Medicine, 388--1 Pungnap-dong, Songpa-gu, Seoul, 138--736, Korea (2) Department of Emergency Medicine, Asan Medical Center, University of Ulsan College of Medicine, 388--1 Pungnap-dong, Songpa-gu, Seoul, Korea (3) Department of Diagnostic Radiology, Asan Medical Center, University of Ulsan College of Medicine, 388--1 Pungnap-dong, Songpa-gu, Seoul, Korea Article History: Registration Date: 15/06/2004 Received Date: 05/11/2003 Accepted Date: 03/06/2004 Online Date: 07/07/2004 Article note: This study was performed with the support of an Asan Medical Center Institutional fund.

Byline: Frans B. Plotz (1), Arthur S. Slutsky (2), Adrianus J. Vught (3), Cobi J. Heijnen (4) Keywords: Biotrauma; Ventilator-induced lung injury; Multiple organ system failure; Compartmentalization; Peripheral immunosuppression; Proapoptotic soluble factors Abstract: Objective To review how biotrauma leads to the development of multiple system organ failure (MSOF). Design and setting Published articles on experimental and clinical studies and review articles in the English language were collected and analyzed. Results The concept that ventilation strategies using 'large' tidal volumes and zero PEEP of injured lungs can enhance injury by the release of inflammatory mediators into the lungs and circulation, a mechanism that has been called biotrauma, is supported by evidence from experimental models ranging from mechanically stressed cell systems, to isolated lungs, intact animals, and humans. Biotrauma may lead to MSOF via spillover of lung-borne inflammatory mediators into the systemic circulation. However, spillover of other agents such as bacteria and soluble proapoptotic factors may also contribute to the onset of MSOF. Other less well studied mechanisms such as peripheral immunosuppression and translocation of bacteria and/or products from the gut may play an important role. Finally, genetic variability is a crucial factor. Conclusions The development of MSOF is a multifactorial process. Our proposed mechanisms linking mechanical ventilation and MSOF suggest several novel therapeutic approaches. However, it will first be necessary to study the mechanisms described above to delineate more precisely the contribution of each proposed factor, their interrelationships, and their time course. We suggest that scientific advances in immunology may offer novel approaches for prevention of MSOF secondary to ventilator-induced lung injury. Author Affiliation: (1) Department of Pediatric Intensive Care, VU Medical Center, P.O. Box 7057, 1007 MB, Amsterdam, The Netherlands (2) Division of Respiratory Medicine, St. Michael's Hospital, Interdepartmental Division of Critical Care, University of Toronto, Toronto, Ontario, Canada (3) Department of Pediatric Intensive Care, University Medical Center Utrecht, Utrecht, The Netherlands (4) Laboratory for Psychoneuroimmunology, University Medical Center Utrecht, Utrecht, The Netherlands Article History: Registration Date: 11/06/2004 Received Date: 07/01/2004 Accepted Date: 01/06/2004 Online Date: 24/06/2004

Byline: Niall D. Ferguson (1,4), Robert M. Kacmarek (2), Jean-Daniel Chiche (3), Jeffrey M. Singh (1), David C. Hallett (1), Sangeeta Mehta (1), Thomas E. Stewart (1) Keywords: Adult respiratory distress syndrome; Artificial respiration; Mechanical ventilation; Anoxemia; Diagnosis Abstract: Objectives The American--European consensus conference (AECC) definition for acute respiratory distress syndrome (ARDS) requires a PaO.sub.2/[F.sub.I][O.sub.2]a$?200 mmHg, regardless of ventilator settings. We report the results of using standardized ventilator settings to screen and enroll ARDS patients in a clinical trial of high-frequency oscillatory ventilation (HFOV), including the impact on study enrollment, and potential effects on study outcome. Design Prospective cohort study. Setting Intensive care units in two teaching hospitals. Participants A consecutive sample of 41 patients with early ARDS by AECC criteria (baseline PaO.sub.2/[F.sub.I][O.sub.2]a$?200) who met all other inclusion/exclusion criteria for the HFOV trial. Interventions Patients were placed on standardized ventilator settings (tidal volume 7--8 ml/kg, PEEP 10 cm[H.sub.2]O, [F.sub.I]O.sub.2 1.0), and the PaO.sub.2/[F.sub.I]O.sub.2 was reassessed after 30 min. Results Seventeen patients (41.5%) had PaO.sub.2/[F.sub.I]O.sub.2 ratios that remained a$?200 mmHg [Persistent ARDS PaO.sub.2/[F.sub.I]O.sub.2=94+-36 (mean+-SD)] and went on to inclusion in the HFOV study however, in 24 patients (58.5%) the PaO.sub.2/[F.sub.I]O.sub.2 was >200 mmHg [Transient ARDS PaO.sub.2/[F.sub.I]O.sub.2=310+-74] and these patients were ineligible for the HFOV study. The ICU mortality was significantly greater (52.9 vs 12.5% p=0.01) in the Persistent ARDS patients. Conclusions The use of these standardized ventilatory significantly impacted the PaO.sub.2/[F.sub.I]O.sub.2 ratio and therefore the ARDS prevalence and trial enrollment. These results have effects on the evaluation of the current ARDS literature and conduct of clinical trials in ARDS and hence consideration should be given to the use of standardized ventilatory settings in future ARDS trials. Author Affiliation: (1) Division of Respirology, Department of Medicine, and the Interdepartmental Division of Critical Care Medicine, University Health Network and Mount Sinai Hospital, University of Toronto, Toronto, Canada (2) Department of Anesthesia and Critical Care, Harvard Medical School, Boston, Massachusetts, USA (3) Paris V University, Paris, France (4) Toronto Western Hospital, 399 Bathurst Street, EC2--024, Toronto, Ontario, M5T 2S8, Canada Article History: Registration Date: 05/01/2004 Received Date: 23/07/2003 Accepted Date: 22/12/2003 Online Date: 28/02/2004 Article note: Electronic Supplementary Material Supplementary Material is available in the online version of this article at http://dx.doi.org/10.1007/s00134-004-2163-2

Byline: John G. Laffey (1), Donall O'Croinin (2), Paul McLoughlin (2), Brian P. Kavanagh (3) Keywords: Hypercapnic acidosis; Mechanical ventilation; Acute lung injury; ARDS; Ventilation-induced lung injury; Buffering Abstract: 'Permissive hypercapnia' is an inherent element of accepted protective lung ventilation. However, there are no clinical data evaluating the efficacy of hypercapnia per se, independent of ventilator strategy. In the absence of such data, it is necessary to determine whether the potential exists for an active role for hypercapnia, distinct from the demonstrated benefits of reduced lung stretch. In this review, we consider four key issues. First, we consider the evidence that protective lung ventilatory strategies improve survival and we explore current paradigms regarding the mechanisms underlying these effects. Second, we examine whether hypercapnic acidosis may have effects that are additive to the effects of protective ventilation. Third, we consider whether direct elevation of CO.sub.2, in the absence of protective ventilation, is beneficial or deleterious. Fourth, we address the current evidence regarding the buffering of hypercapnic acidosis in ARDS. These perspectives reveal that the potential exists for hypercapnia to exert beneficial effects in the clinical context. Direct administration of CO.sub.2 is protective in multiple models of acute lung and systemic injury. Nevertheless, several specific concerns remain regarding the safety of hypercapnia. At present, protective ventilatory strategies that involve hypercapnia are clinically acceptable, provided the clinician is primarily targeting reduced tidal stretch. There are insufficient clinical data to suggest that hypercapnia per se should be independently induced, nor do outcome data exist to support the practice of buffering hypercapnic acidosis. Rapidly advancing basic scientific investigations should better delineate the advantages, disadvantages, and optimal use of hypercapnia in ARDS. Author Affiliation: (1) Department of Anaesthesia, University College Hospital, Galway and Clinical Sciences Institute, National University of Ireland, Galway, Ireland (2) Department of Physiology, University College Dublin, Dublin, Ireland (3) Department of Critical Care Medicine and The Lung Biology Program, The Research Institute, The Hospital for Sick Children and Program in Critical Care Medicine, University of Toronto, Toronto, Canada Article History: Registration Date: 01/10/2003 Received Date: 16/06/2003 Accepted Date: 29/09/2003 Online Date: 14/01/2004

Byline: Daniel A. Lichtenstein (1,2,3), Nathalie Lascols (2), Gilbert Meziere (1,2,3), Agnes Gepner (3) Keywords: Chest ultrasonography; Ultrasound diagnosis; Lungs; Respiratory failure; Alveolar consolidation; Intensive care unit Abstract: Objective Alveolar consolidation is a basic concern in critically ill patients. Radiography is not a precise tool, and referral to CT raises problems (transport, irradiation). The aim of this study was to assess the utility of ultrasound in the diagnosis of alveolar consolidation. Design Prospective clinical study. Setting The medical ICU of a university-affiliated teaching hospital. Patients A total of 65 cases of alveolar consolidation proven on CT were compared to 53 CT controls. Measurements Alveolar consolidation was defined as a tissue-like pattern visible at the chest wall, arising from the pleural line and devoid of centrifugal inspiratory dynamics. Results Feasibility was 99%. In 65 cases of alveolar consolidation, ultrasound was positive in 59 and negative in 6. In 52 analyzable controls, ultrasound was negative in 51 and positive in 1. Sensitivity of ultrasound was 90% and specificity 98%. A concordance test showed a Kappa coefficient of 0.89. Among 62 posterior locations on CT, ultrasound showed posterior consolidation patterns in 56 cases and was negative in 6. Ultrasound showed anterior involvement in all 3 cases of whole lung consolidation. Conclusions Ultrasound provides a reliable non-invasive, bedside method for accurate detection and location of alveolar consolidation in critically ill patients. Author Affiliation: (1) Service de Reanimation Medicale, Hopital Ambroise-Pare, 9 avenue du General Charles-de-Gaulle, 92100 , Boulogne (Paris-Ouest), France (2) Cercle des Echographistes d'Urgence et de Reanimation Francophones, 14 rue Alfred Couturier, 78160 , Marly, France (3) Service de Reanimation Polyvalente, Centre Hospitalier General, 92210 , Saint-Cloud (Paris), France Article History: Registration Date: 23/10/2003 Received Date: 20/06/2003 Accepted Date: 20/10/2003 Online Date: 13/01/2004 Article note: An editorial regarding this article can be found in the same issue ( http://dx.doi.org/10.1007/s00134-003-2083-6)