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Both high tidal volume mechanical ventilation (HV) and hyperoxia (HO) have been implicated in ventilator-induced lung injury. However, patients with acute lung injury are often exposed to HO before the application of mechanical ventilation. The potential priming of the lungs for subsequent injury by exposure to HO has not been extensively studied. We provide evidence that HO (90%) for 12 h followed by HV (25 [micro]l/g) combined with HO for 2 or 4 h (HO-12h+HVHO-2h or -4h) induced severe lung injury in mice. Analysis of lung homogenates showed that lung injury was associated with cleavage of executioner caspases, caspases-3 and -7, and their downstream substrate poly(ADP-ribose) polymerase-1 (PARP-1). No significant lung injury or caspase cleavage was seen with either HO for 16 h or HV for up to 4 h. Ventilation for 4 h with HO (HVHO) did not cause significant lung injury without preexposure to HO. Twelve-hour HO followed by lower tidal volume (6 [micro]l/g) mechanical ventilation failed to produce significant injury or caspase cleavage. We also evaluated the initiator caspases, caspases-8 and -9, to determine whether the death receptor or mitochondrial-mediated pathways were involved. Caspase-9 cleavage was observed in HO-12h+HVHO-2h and -4h as well as HO for 16 h. Caspase-8 activation was observed only in HO-12h+HVHO-4h, indicating the involvement of both pathways. Immunohistochemistry and in vitro stretch studies showed caspase cleavage in alveolar epithelial cells. In conclusion, preexposure to HO followed by HV produced severe lung injury associated with alveolar epithelial cell apoptosis. mechanical ventilation; mouse doi: 10.1152/ajplung.00072.2010.

Byline: Zhanqi Zhao (1,2,4), Knut Moller (2), Daniel Steinmann (1), Inez Frerichs (3), Josef Guttmann (1) Keywords: Inhomogeneity index; Electrical impedance tomography; Pulmonary ventilation distribution; Ventilation therapy Abstract: Purpose To evaluate the plausibility, stability, and interindividual comparability of the global inhomogeneity index (GI) based on electrical impedance tomography (EIT). Methods The lung area in an EIT image was identified by using the lung area estimation method, which mirrors the lung regions in the functional EIT image and subsequently subtracts the cardiac-related areas. The tidal EIT image, showing the difference in impedances between end-inspiration and end-expiration, was calculated and the variations in its pixel values within the predefined lung area were then used as an indicator of inhomogeneous ventilation (the GI index). Fifty patients were investigated including 40 patients tracheally intubated with double-lumen tubes (test group) and 10 patients under anesthesia without pulmonary disease (control group). Positive end-expiratory pressure (PEEP) of 5 mbar was applied in the test group during both two-lung ventilation (TLV) and subsequent one-lung ventilation (OLV). The patients of the control group were ventilated without PEEP. EIT data were recorded in both groups. Results A significantly lower GI value was found in the control group (0.40 +- 0.05, P = 0.025 vs. TLV 0.74 +- 0.47 and P < 0.002 vs. OLV 1.51 +- 1.45). A significant difference was also found in the test group between TLV and OLV (P < 0.002). If GI was calculated only in the ventilated lung area during OLV (0.71 +- 0.32), it did not significantly differ from the test group during TLV. Conclusions The GI index quantifies the gas distribution in the lung with a single number and reveals good interpatient comparability. Author Affiliation: (1) Section for Experimental Anesthesiology, Department of Anesthesiology and Critical Care Medicine, University Medical Center, Freiburg, Germany (2) Department of Biomedical Engineering, Furtwangen University, Villingen-Schwenningen, Germany (3) Department of Anesthesiology and Intensive Care Medicine, University Medical Center of Schleswig-Holstein Campus Kiel, Kiel, Germany (4) Sektion fur Experimentelle Anaesthesiologie, Anaesthesiologische Universitatsklinik Freiburg, Hugstetter Strasse 55, 79106, Freiburg, Germany Article History: Registration Date: 14/07/2009 Received Date: 10/02/2009 Accepted Date: 25/06/2009 Online Date: 04/08/2009 Article note: The results of this study were presented in part at the European Biomedical Engineering Congress (EMBEC 2008) in Antwerp, Belgium. Electronic supplementary material The online version of this article (doi: 10.1007/s00134-009-1589-y) contains supplementary material, which is available to authorized users.

Byline: Fabio Ferrari (1,2), Qin Lu (1,2), Cassio Girardi (3), Olivier Petitjean (4), Charles-Hugo Marquette (5), Frederic Wallet (6), Jean-Jacques Rouby (1,2) Keywords: Nebulization; Ceftazidime; Pneumonia; Pseudomonas aeruginosa; Mechanical ventilation; Treatment Abstract: Purpose Ventilator-associated pneumonia caused by Pseudomonas aeruginosa with impaired sensitivity to ceftazidime is frequent in critically ill patients. The aim of the study was to compare lung tissue deposition and antibacterial efficiency between nebulized and intravenous administrations of ceftazidime in ventilated piglets with pneumonia caused by Pseudomonas aeruginosa with impaired sensitivity to ceftazidime. Methods Ceftazidime was administered 24 h following the intra-bronchial inoculation of Pseudomonas aeruginosa (minimum inhibitory concentration = 16 ug ml.sup.-1), either by nebulization (25 mg kg.sup.-1 every 3 h, n = 6) or by continuous intravenous infusion (90 mg kg.sup.-1 over 24 h after an initial rapid infusion of 30 mg kg.sup.-1, n = 6). Four non-treated inoculated animals served as controls. All piglets were killed 48 h (intravenous and control groups) or 51 h (aerosol group) after inoculation. Lung tissue concentrations and lung bacterial burden were assessed on multiple post-mortem sub-pleural lung specimens [(lower limit of quantitation = 10.sup.2 colony forming unit (cfu g.sup.-1)]. Results Ceftazidime trough lung tissue concentrations following nebulization were greater than steady-state lung tissue concentrations following continuous intravenous infusion [median and interquartile range, 24.8 (12.6--59.6) ug g.sup.-1 vs. 6.1 (4.6--10.8) ug g.sup.-1] (p < 0.001). After 24 h of ceftazidime administration, 83% of pulmonary segments had bacterial counts Conclusion Nebulized ceftazidime provides more efficient bacterial killing in ventilated piglets with pneumonia caused by Pseudomonas aeruginosa with impaired sensitivity to ceftazidime. Author Affiliation: (1) Reanimation Polyvalente Pierre Viars, Departement d'Anesthesie-Reanimation, UPMC Univ Paris 06, Hopital Pitie-Salpetriere, Assistance Publique-Hopitaux de Paris, 47-83 boulevard de l'Hopital, 75013, Paris, France (2) Polyvalent Intensive Care Unit Pierre Viars, La Pitie-Salpetriere Hospital, University Pierre et Marie Curie, Paris, France (3) Department of Anesthesiology, Federal University of Sao Paulo, Escola Paulista de Medicina, Sao Paulo, Brazil (4) Department of Pharmacology, Avicenne Hospital, Bobigny, France (5) DHURE and INSERM U 416, University of Medicine, Lille, France (6) Department of Bacteriology, University of Medicine, Lille, France Article History: Registration Date: 17/07/2009 Received Date: 03/03/2009 Accepted Date: 08/07/2009 Online Date: 04/08/2009

Byline: Jurgen Barwing (1), Markus Ambold (1), Nadine Linden (1), Michael Quintel (1), Onnen Moerer (1) Keywords: Neurally adjusted ventilatory assist (NAVA); Neural control; Electrical activation of the diaphragm (EAdi) Abstract: Purpose During neurally adjusted ventilatory assist (NAVA) the ventilator is driven by the patients electrical activation of the diaphragm (EAdi), detected by a special esophageal catheter. A reliable positioning of the EAdi-catheter is mandatory to trace a representative EAdi signal. We aimed to determine whether a formula that is based on the measurement from nose to ear lobe to xiphoid process of the sternum (NEX distance) modified for EAdi-catheter placement (NEX.sub.mod) is sufficient for predicting the accurate catheter position. Methods Twenty-six patients were enrolled in this study. The optimal EAdi-catheter position (OPT) was defined by: (1) stable EAdi signal, (2) electrical activity highlighted in central leads of the catheter positioning tool, and (3) absence of p-wave in distal lead. Afterwards NEX.sub.mod was calculated and compared to the OPT finding. Results At NEX.sub.mod the EAdi signal was suitable for running NAVA in 18 out of 25 patients (72%). NEX.sub.mod was identical with OPT in four patients (16%). NAVA was possible in all patients at OPT. Median OPT position was 2 cm caudal of the NEX.sub.mod ranging from 3 cm too cranial to a position 12 cm too caudal (P < 0.01). In one patient excluded from further analysis EAdi-catheter placement led to the diagnosis of bilateral injury of the phrenic nerves. Conclusions EAdi-catheter placement based on the NEX.sub.mod formula allows running NAVA in about two-thirds of all patients. The additional tools provided are efficient and facilitate the correct positioning of the EAdi-catheter for neurally adjusted ventilatory assist. Author Affiliation: (1) Department of Anaesthesiology, Emergency and Intensive Care Medicine, Georg-August University of Gottingen, Robert-Koch-Str. 40, 37075, Gottingen, Germany Article History: Registration Date: 14/07/2009 Received Date: 26/04/2009 Accepted Date: 09/07/2009 Online Date: 04/08/2009

Byline: Nectaria Xirouchaki (1), Eumorfia Kondili (1), Maria Klimathianaki (1), Dimitris Georgopoulos (1) Keywords: Ventilator settings; Sedatives; Analgesics; Vasoactive medications; Critically ill Abstract: Objectives The aim of this study was to compare the number of interventions (ventilator settings and sedatives, analgesics and vasoactive medication dose manipulations) between critically ill patients on proportional-assist ventilation with load-adjustable gain factors (PAV+) and those on pressure support (PS). Design Retrospective analysis of data from a previous randomized clinical trial. Methods A total of 208 patients who were mechanically ventilated on controlled modes and met criteria for assisted breathing were randomized to receive either PS (n = 100) or PAV+ (n = 108). Changes in ventilator settings and in the dose of sedatives, analgesics, and vasoactive medications were identified during the period in which the patients were ventilated either with PS (30.4 +- 17.4 h) or PAV+ (30.0 +- 18.1 h) and classified as changes to facilitate weaning (CFW) or changes to respond to deterioration (CD). Results The mean number of changes in ventilator settings was significantly higher with PS than that with PAV+ (10.7 +- 5.7 vs. 8.9 +- 4.6). With PS the proportion of these changes classified as CFW was significantly lower than that with PAV+ (59.8% vs. 69.2%). Dyssynchrony as a cause of CD was more likely to occur with PS than with PAV+ (42 vs. 3%). The mean number of changes in the dose of sedatives, analgesics, and vasoactive medications was higher with PS than with PAV+, the difference being significant only for sedatives (4.06 +- 3.8 vs. 2.82 +- 3.4). Conclusions Compared to PS, PAV+ is associated with fewer intervention in terms of ventilator settings and sedative dose changes. Author Affiliation: (1) Department of Intensive Care Medicine, University Hospital of Heraklion, Medical School, University of Crete, Heraklion, Crete, Greece Article History: Registration Date: 28/05/2009 Received Date: 19/03/2009 Accepted Date: 20/05/2009 Online Date: 16/06/2009 Article note: Electronic supplementary material The online version of this article (doi: 10.1007/s00134-009-1524-2) contains supplementary material, which is available to authorized users.

Byline: Javier Hortal (1), Maddalena Giannella (2), Maria Jesus Perez (1), Jose Maria Barrio (1), Manuel Desco (3), Emilio Bouza (2,4), Patricia Munoz (2,4) Keywords: Ventilator-associated pneumonia; Heart surgery; Nosocomial infection; Nosocomial pneumonia; Risk factors for ICU nosocomial infection Abstract: Purpose Major heart surgery (MHS) patients are a particularly high-risk population for nosocomial infections. Our objective was to identify risk factors for ventilator-associated pneumonia (VAP) in patients undergoing MHS. Methods Prospective study including 1,844 patients operated from 2003 to 2006. Results Overall 106 patients (140 episodes) developed one or more episodes of VAP (5.7%, 22.2 episodes per 1,000 days of mechanical ventilation). VAP incidence was 45.9% in those patients requiring more than 48 h of MV. Enterobacteriaceae (32.8), Pseudomonas aeruginosa (28.6%) and Staphylococcus aureus (27.1%, of which 65.8% were methicillin resistant) were the principal microorganisms causing VAP. The independent risk factors for VAP were: age >70, perioperative transfusions, days of mechanical ventilation, reintubation, previous cardiac surgery, emergent surgery and intraoperative inotropic support. Median length of stay in the ICU for patients who developed VAP or not was, respectively, 25.5 versus 3 days (P < 0.001), and mortality was, respectively, 45.7 versus 2.8% in both populations (P < 0.001). We developed a predictive preoperative score with a sensitivity of 93% and a specificity of 40%. Conclusions VAP is common in patients undergoing MHS that require more than 48 h of MV. In that 'high-risk' population, innovative preventive measures should be developed and applied. Author Affiliation: (1) Department of Anesthesia, Hospital General Universitario Gregorio Maranon, Madrid, Spain (2) Department of Clinical Microbiology and Infectious Diseases, Hospital General Universitario Gregorio Maranon, Madrid, Spain (3) Department of Experimental Medicine, Hospital General Universitario Gregorio Maranon, Doctor Esquerdo 46, 28007, Madrid, Spain (4) CIBER de Enfermedades Respiratorias (CIBERES), Barcelona, Spain Article History: Registration Date: 28/05/2009 Received Date: 14/09/2008 Accepted Date: 06/03/2009 Online Date: 26/06/2009 Article note: This article is discussed in the editorial available at: doi: 10.1007/s00134-009-1522-4.

Our aim was to develop a computerized system for real-time monitoring of lung mechanics measurements during both gas and liquid ventilation. System accuracy was demonstrated by calculating regression and percent error of the following parameters compared to standard device: airway pressure difference ([DELTA][P.sub.aw]), respiratory frequency ([f.sub.R]), tidal volume ([V.sub.T]), minute ventilation ([V'.sub.E]), inspiratory and expiratory maximum flows ([V'.sub.ins, max], [V'.sub.exp, max]), dynamic lung compliance ([C.sub.L,dyn]), resistance of the respiratory system calculated by method of Mead-Whittenberger ([R.sub.rs,MW]) and by equivalence to electrical circuits ([R.sub.rs, ele]), work of breathing ([W.sub.OB]), and overdistension. Outcome measures were evaluated as function of gas exchange, cardiovascular parameters, and lung mechanics including mean airway pressure ([mP.sub.aw]). [DELTA][P.sub.aw], [V.sub.T], [V'.sub.ins, max], [V'.sub.exp, max], and [V'.sub.E] measurements had correlation coefficients r = 1.00, and %error < 0.5%. [f.sub.R], [C.sub.L,dyn], [R.sub.rs,MW], [R.sub.rs, ele], and [W.sub.OB] showed r [greater than or equal to] 0.98 and %error < 5%. Overdistension had r = 0.87 and %error < 15%. Also, resistance was accurately calculated by a new algorithm. The system was tested in rats in which lung lavage was used to induce acute respiratory failure. After lavage, both gas- and liquid-ventilated groups had increased [mP.sub.aw] and [W.sub.OB], with decreased [V.sub.T], [V'.sub.E], [C.sub.L,dyn], [R.sub.rs,MW] , and [R.sub.rs,ele] compared to controls. After 1-h ventilation, both injured group had decreased [V.sub.T], [V'.sub.E], and [C.sub.L,dyn], with increased [mP.sub.aw], [R.sub.rs,MW], [R.sub.rs,ele], and [W.sub.OB]. In lung-injured animals, liquid ventilation restored gas exchange, and cardiovascular and lung functions. Our lung mechanics system was able to closely monitor pulmonary function, including during transitions between gas and liquid phases. Index Terms--Compliance, dynamic lung mechanics, inertance, quasi-static lung mechanics, resistance, total liquid ventilation (TLV).

Although the vascular bed is a major source of nitric oxide (NO) production, factors regulating the production remain unclear. We considered the role played by paracrine signaling. Determinations by fluorescence microscopy in isolated, blood-perfused rat and mouse lungs revealed that a brief lung expansion enhanced cytosolic [Ca.sup.2+] ([Ca.sup.2+]cyt) oscillations in alveolar epithelial (AEC) and endothelial (EC) cells, and NO production in EC. Furthermore, as assessed by a novel microlavage assay, alveolar ATP production increased. Intra-alveolar microinfusion of the purinergic receptor antagonist, PPADS, and the nucleotide hydrolyzing enzyme, apyrase, each completely blocked the [Ca.sup.2+]cyt and NO responses in EC. Lung expansion induced [Ca.sup.2+]cyt oscillations in mice lacking the P2Y1, but not the P2Y2, purinergic receptors, which were located in the perivascular interstitium basolateral to AEC. Prolonged lung expansion instituted by mechanical ventilation at high tidal volume increased EC expression of nitrotyrosine, indicating development of nitrosative stress in lung microvessels. These findings reveal a novel mechanism in which mechanically induced purinergic signaling couples cross-compartmental [Ca.sup.2+]cyt oscillations to micro-vascular NO production. pulmonary circulation; calcium; DAF; imaging; fluorescence

Byline: Leticia Martinez-Caro (1), Jose A. Lorente (1), Judith Marin-Corral (1,2), Carolina Sanchez-Rodriguez (1), Alberto Sanchez-Ferrer (1), Nicolas Nin (1), Antonio Ferruelo (1), Marta Paula (1), Pilar Fernandez-Segoviano (1), Esther Barreiro (1,2), Andres Esteban (1) Keywords: Mechanical ventilation; Tidal volume; Lung injury; Vascular dysfunction; Oxygen reactive species; Nitrogen reactive species Abstract: Objective To demonstrate that increased formation of reactive oxygen (ROS) and nitrogen species (RNS) is involved in VILI-induced vascular dysfunction. Methods Male Sprague-Dawley anesthetized rats were ventilated for 60 min using low V.sub.T ventilation [V.sub.T 9 ml/kg, positive end-expiratory pressure (PEEP) 5 cm[H.sub.2]O, n = 18], and high V.sub.T ventilation (V.sub.T 35 ml/kg, zero PEEP, n = 18). Arterial pressure and respiratory system mechanics were monitored. Blood samples for the determination of arterial blood gases and lactate concentration were drawn. Vascular rings from the thoracic aortae were mounted in organ baths for isometric tension recording. We studied endothelium-dependent relaxation in norepinephrine-precontracted rings (acetylcholine, 10 nM--10 uM) and contraction induced by norepinephrine (1 nM--10 uM) in resting vessels. Vascular rings were preincubated for 30 min with Zn--Mn--SOD (100 u/ml) or tempol (10.sup.-4 M) (extracellular and intracellular superoxide scavengers, respectively) or MnTMPyP (10.sup.-5 M) (a superoxide and peroxynitrite scavenger). The presence of superoxide and nitrotyrosine in aortic rings was evaluated by immunofluorescence. Results High V.sub.T ventilation induced hypotension, systemic acidosis, hypoxemia and hyperlactatemia, as well as impairment in acetylcholine and norepinephrine-induced responses in vitro. Responses to acetylcholine were improved by tempol (P = 0.004) and completely corrected (P < 0.001) by MnTMPyP. Responses to norepinephrine were also improved by treatment with tempol (P < 0.001) and MnTMPyP (P < 0.001). However, Zn--Mn--SOD did not improve acetylcholine- or norepinephrine-induced responses. Immunostaining for both superoxide and nitrotyrosine was increased in aortic rings from the high V.sub.T group. Conclusions Our data support a role for intracellular ROS and peroxynitrite in the high V.sub.T ventilation-induced vascular dysfunction. Author Affiliation: (1) Centro de Investigacion en Red de Enfermedades Respiratorias (CibeRes), Hospital Universitario de Getafe, Universidad Europea de Madrid, Carretera de Toledo, km 12.500, Getafe, 28905, Madrid, Spain (2) Pulmonology Department-URMAR, IMIM-Hospital del Mar, CIBERES, CEXS, Universitat Pompeu Fabra (UPF), PRBB, C/Dr. Aiguader, 88, 08003, Barcelona, Spain Article History: Registration Date: 23/03/2009 Received Date: 10/09/2008 Accepted Date: 17/03/2009 Online Date: 10/04/2009 Article note: Electronic supplementary material The online version of this article (doi: 10.1007/s00134-009-1469-5) contains supplementary material, which is available to authorized users.

Byline: Francois Lellouche (1,2,5), Salvatore Maurizio Maggiore (1,3), Aissam Lyazidi (1), Nicolas Deye (1,4), Solenne Taille (1), Laurent Brochard (1) Keywords: Mechanical ventilation; Non-invasive ventilation; Heated humidifiers; Heat and moisture exchangers; Humidification; Psychrometry Abstract: Introduction No clear recommendation exists concerning humidification during non-invasive ventilation (NIV) and high flow CPAP, and few hygrometric data are available. Methods We measured hygrometry during NIV delivered to healthy subjects with different humidification strategies: heated humidifier (HH), heat and moisture exchanger, (HME) or no humidification (NoH). For each strategy, a turbine and an ICU ventilator were used with different FiO.sub.2 settings, with and without leaks. During CPAP, two different HH and NoH were tested. Inspired gases hygrometry was measured, and comfort was assessed. On a bench, we also assessed the impact of ambient air temperature, ventilator temperature and minute ventilation on HH performances (with NIV settings). Results During NIV, with NoH, gas humidity was very low when an ICU ventilator was used (5 mg[H.sub.2]O/l), but equivalent to ambient air hygrometry with a turbine ventilator at minimal FiO.sub.2 (13 mg[H.sub.2]O/l). HME and HH had comparable performances (25--30 mg[H.sub.2]O/l), but HME's effectiveness was reduced with leaks (15 mg[H.sub.2]O/l). HH performances were reduced by elevated ambient air and ventilator output temperatures. During CPAP, dry gases (5 mg[H.sub.2]O/l) were less tolerated than humidified gases. Gases humidified at 15 or 30 mg[H.sub.2]O/l were equally tolerated. Conclusion This study provides data on the level of humidity delivered with different humidification strategies during NIV and CPAP. HH and HME provide gas with the highest water content. Comfort data suggest that levels above 15 mg[H.sub.2]O/l are well tolerated. In favorable conditions, HH and HMEs are capable of providing such values, even in the presence of leaks. Author Affiliation: (1) Service de Reanimation Medicale, Assistance Publique-Hopitaux de Paris, Centre Hospitalier Albert Chenevier, Henri Mondor, Universite Paris 12, Creteil, INSERM U 955, Creteil, France (2) Service de soins intensifs de chirurgie cardiaque, Centre de recherche Institut Universitaire de Cardiologie et de Pneumologie de Quebec, Universite Laval, Quebec, Canada (3) Istituto di anestesiologia e Rianimazione, Universita Cattolica Policlinico A.Gemelli, Rome, Italy (4) Service de Reanimation Medicale, Hopital Lariboisiere, Assistance Publique-Hopitaux de Paris, Paris, France (5) Centre de recherche Institut Universitaire de Cardiologie et de Pneumologie de Quebec, Universite Laval, 2725, chemin Sainte-Foy, Quebec, G1V4G5, Canada Article History: Registration Date: 25/02/2009 Received Date: 28/07/2008 Accepted Date: 29/01/2009 Online Date: 18/03/2009 Article note: This article is discussed in the editorial available at: doi: 10.1007/s00134-009-1457-9. Presented in part at the 2003 American Thoracic Society meeting, 16--21 May, Seattle. Electronic supplementary material The online version of this article (doi: 10.1007/s00134-009-1455-y) contains supplementary material, which is available to authorized users.

Byline: Steffen Weber-Carstens (1), Sven Bercker (2), Matthias Hommel (1), Maria Deja (1), Martin MacGuill (1), Christiane Dreykluft (3), Udo Kaisers (2) Keywords: Late-phase ARDS; Hypercapnia; Low tidal volume ventilation; Ventilator-induced lung injury; Shear stress; Pumpless extracorporeal lung assist; Sedation; Assisted spontaneous breathing Abstract: Objective The fibroproliferative phase of late ALI/ARDS as described by Hudson and Hough (Clin Chest Med 27:671--677, 2006) is associated with pronounced reductions in pulmonary compliance and an accompanying hypercapnia complicating low tidal volume mechanical ventilation. We report the effects of extracorporeal CO.sub.2 removal by means of a novel pumpless extracorporeal lung assist (p-ECLA) on tidal volumes, airway pressures, breathing patterns and sedation management in pneumonia patients during late-phase ARDS. Design Retrospective analysis. Setting Fourteen-bed university hospital ICU. Patients Ten consecutive late-phase ALI/ARDS patients with low pulmonary compliance, and severe hypercapnia. Intervention Gas exchange, tidal volumes, airway pressures, breathing patterns and sedation requirements before (baseline) and after (2--4 days) initiation of treatment with p-ECLA were analysed. Patients were ventilated in a pressure-controlled mode with PEEP adjusted to pre-defined oxygenation goals. Measurements and main results Median reduction in pCO.sub.2 was 50% following institution of p-ECLA. Extracorporeal CO.sub.2 removal enabled significant reduction in tidal volumes (to below 4 ml/kg predicted body weight) and inspiratory plateau pressures [30 (28.5/32.3) cm[H.sub.2]O, median 25, 75% percentiles]. Normalization of pCO.sub.2 levels permitted significant reduction in the dosages of analgesics and sedatives. The proportion of assisted spontaneous breathing increased within 24 h of instituting p-ECLA. Conclusion Elimination of CO.sub.2 by p-ECLA therapy allowed reduction of ventilator-induced shear stress through ventilation with tidal volumes below 4 ml/kg predicted body weight in pneumonia patients with severely impaired pulmonary compliance during late-phase ARDS. p-ECLA treatment supported control of breathing pattern while sedation requirements were reduced and facilitated the implementation of assisted spontaneous breathing. Author Affiliation: (1) Department of Anesthesiology and Intensive Care Medicine, Charite, Universitatsmedizin Berlin, Campus Virchow-Klinikum, Campus Mitte, Berlin, Germany (2) Department of Anesthesiology and Intensive Care Medicine, Medical Faculty, University of Leipzig, Leipzig, Germany (3) Department of Internal Medicine, Klinikum Braunschweig, Braunschweig, Germany Article History: Registration Date: 19/01/2009 Received Date: 27/06/2008 Accepted Date: 10/01/2009 Online Date: 31/01/2009

Byline: Pascal Beuret (1), Christophe Roux (1), Annie Auclair (1), Karim Nourdine (1), Mahmoud Kaaki (1), Marie-Jose Carton (1) Keywords: Extubation; Cough strength; Peak cough expiratory flow; Electronic flowmeter Abstract: Purpose This study aimed to evaluate an objective measure of cough strength, the peak cough expiratory flow (PCEF), as a predictive criterion of success or failure of extubation. Methods Patients under mechanical ventilation for more than 24 h who successfully passed the spontaneous breathing trial were included in the study. Just before extubation, PCEF was measured with an electronic flowmeter. Results A total of 130 patients were included. The median duration of mechanical ventilation before extubation was 8 days (4--17). Fourteen patients (10.8%) failed extubation. The sole factor significantly associated with extubation failure was the measure of PCEF. The patients who did not cough at order had a higher rate of extubation failure than those who did (P = 0.03). The mean PCEF of patients who failed extubation (36.3 +- 15 l/min) was significantly lower than the one of patients who succeeded (63.6 +- 32 l/min) (P < 0.001). The optimal cut-off value of PCEF was 35 l/min. Overall, an inability to cough at order or a PCEF a$?35 l/min predicted extubation failure with a sensitivity of 79% and a specificity of 71%. The risk of extubation failure was 24% for the patients who did not cough at order or with a PCEF a$?35 l/min and 3.5% for those with a PCEF >35 l/min [RR = 6.9 (95% CI, 2--24) P = 0.002]. Conclusions This study confirmed the interest of measuring the PCEF to predict extubation outcome in patients having successfully passed the spontaneous breathing trial. Author Affiliation: (1) Intensive Care Unit, Centre Hospitalier Roanne, 28 rue de Charlieu, 42328, Roanne, France Article History: Registration Date: 13/01/2009 Received Date: 04/08/2008 Accepted Date: 22/12/2008 Online Date: 24/01/2009

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: Michael Darmon (1,3,5), Frederique Schortgen (1), Rusel Leon (1), Stephane Moutereau (4), Julien Mayaux (1), Fabiano Marco (1,3), Jerome Devaquet (1,3), Christian Brun-Buisson (1,2,3), Laurent Brochard (1,2,3) Keywords: Intensive care unit; Respiratory distress syndrome, adult; Urinary tract physiology; Renal failure, acute; Doppler ultrasonography Abstract: Rationale Short-term hypoxemia affects diuresis and natriuresis in healthy individuals. No data are available on the impact of the mild hypoxemia levels usually tolerated in critically ill patients receiving mechanical ventilation. Objectives To assess the renal effects of mild hypoxemia during mechanical ventilation for acute lung injury (ALI). Methods Prospective, physiological study in 12 mechanically ventilated patients with ALI. Patients were studied at baseline with an arterial saturation (SaO.sub.2) of 96% [94--98] then a comparison was performed between SaO.sub.2 values of 88--90% (mild hypoxemia) and 98--99% (high oxygenation). Main results FiO.sub.2 was set at 0.25 [0.23--0.32] and 0.7 [0.63--0.8], respectively, to obtain SaO.sub.2 of 89 [89--90] and 99% [98--99]. Hemodynamic or respiratory parameters were not significantly affected by FiO.sub.2 levels. Compared with high oxygenation level, mild hypoxemia using low FiO.sub.2 was associated with increase in diuresis (median [interquartile range], 67 [55--105] vs. 55 [45--60] ml/h P = 0.003) and in doppler-based renal resistive index (RI) (0.78 [0.66--0.85] vs. 0.72 [0.60--0.78] P = 0.003). The 2-h calculated creatinine clearance also increased (63 [46--103] vs. 35 [30--85] ml/min P = 0.005) without change in urinary creatinine (P = 0.13). No significant change in natriuresis was observed. Half of the patients were under norepinephrine infusion and the renal response did not differ according to the presence of vasopressors. Conclusion In patients with ALI, mild hypoxemia related to short-term low FiO.sub.2 induce increases in diuresis and in renal RI. This latter point suggests intra-renal mechanisms that need to be further investigated. Author Affiliation: (1) Medical Intensive Care Unit, AP-HP, Centre hospitalier Albert Chenevier, Henri Mondor, Creteil, France (2) Paris XII University, Creteil, France (3) INSERM Unit 955, Creteil, France (4) Department of Biochemistry, AP-HP, Centre hospitalier Albert Chenevier, Henri Mondor, Creteil, France (5) Medical Intensive Care Unit, AP-HP, Saint-Louis University Hospital, 1 avenue Claude Vellefaux, 75010, Paris, France Article History: Registration Date: 04/12/2008 Received Date: 18/05/2008 Accepted Date: 23/10/2008 Online Date: 26/02/2009 Article note: Electronic supplementary material The online version of this article (doi: 10.1007/s00134-008-1372-5) contains supplementary material, which is available to authorized users.

Galanin is present in neurons in the brain that are important in the control of arterial pressure, and intracisternal administration of galanin evokes hypotension, but the site of action is unknown. In urethane-anesthetized, vagotomized mechanically ventilated Sprague-Dawley rats (n = 34), we investigated the effects of microinjecting galanin (1 mM, 50 nl, 50 pmol) into the rostral ventrolateral medulla on resting splanchnic sympathetic nerve activity, arterial pressure, heart rate, and phrenic nerve activity. Second, we determined the effect of microinjecting galanin into the rostral ventrolateral medulla on the cardiovascular response to stimulation of central and peripheral chemoreceptors, arterial baroreceptors, and the somatosympathetic reflex. Galanin caused a prolonged reduction in resting splanchnic sympathetic nerve activity (-37.0 [+ or -] 7.2% of baseline), mean arterial pressure (-17.0 [+ or -] 3.5 mmHg), and heart rate (-25.0 [+ or -] 9.1 beats/min). Galanin increased the sympathoinhibitory response to aortic depressor nerve stimulation by 51.8%, had no effect on the somatosympathetic reflex, and markedly attenuated the effect of hypercapnia and hypoxia on arterial pressure (by 65% and 92.4% of control, respectively). These results suggest a role for galanin neurotransmission in the integration of the cardiovascular responses to hypoxia, hypercapnia, and the sympathetic baroreflex in the rostral ventrolateral medulla. The data suggest that galanin may be an important peptide in the homeostatic regulation of chemosensory reflexes. baroreflex; somatosympathetic reflex; hypercapnia; hypoxia

Within continuously controlled limits of cuff pressure, an endotracheal tube cuff made of polyurethane (PU) prevents secretion inflow better than a conventional polyvinylchloride cuff. However, the temperature difference between ventilator gas and the air inside a PU cuff produces condensation droplets that accumulate in the cuff inflation canal. We investigated whether condensation influenced continuous cuff pressure monitoring. A PU-cuffed tube was placed into an artificial trachea and connected to a ventilator and test lung. An additional line was inserted at the distal cuff end to directly measure pressure inside the cuff. Methylene blue instillation via the inflation line mimicked condensation. Inspiratory (Pinsp) and expiratory (Pexp) pressures were continuously recorded. Six consecutive experiments were performed comparing pressures at baseline (T0) and at 24 h (T24). Shortly after dye instillation, pressures recorded at the inflation canal became permanently fixed at 25 cm[H.sub.2]O. In contrast, pressures measured directly in the cuff progressively decreased (mean Pinsp 30 ± 3 vs. 20 ± 2 cm[H.sub.2]O and mean Pexp 25 ± 0 vs. 12 ± 2 cm[H.sub.2]O, T0 vs. T24, both P < 0.05). Thus, condensation in the inflation line of a PU-cuffed tube renders continuous cuff pressure monitoring unreliable, thereby increasing the risk for microaspiration. Keywords Tracheal cuff * Cuff pressure * Polyurethane * Microaspiration, Microaspiration of bacteria-colonized secretions from the subglottic space into the lower airways represents one of the leading pathogenic pathways of tracheobronchitis and subsequent pneumonia in mechanically ventilated patients [1]. The [...]

Endothelial nitric oxide (NO) synthase (eNOS) expression and activity are decreased in fetal lambs with persistent pulmonary hypertension (PPHN). We sought to determine the impact of mechanical ventilation with [O.sub.2] with or without inhaled NO (iNO) or recombinant human SOD (rhSOD) on eNOS in the ductal ligation model of PPHN. PPHN lambs and age-matched controls were ventilated with 100% [O.sub.2] for 24 h alone or combined with 20 ppm iNO continuously or a single dose of rhSOD (5 mg/kg) given intratracheally at delivery. In 1-day spontaneously breathing lambs, eNOS expression in resistance pulmonary arteries increased relative to fetal levels, eNOS expression increased in control lambs ventilated with 100% [O.sub.2], but not in PPHN lambs. Addition of iNO or rhSOD increased eNOS expression and decreased generation of reactive oxygen species (ROS) in PPHN lambs relative to those ventilated with 100% [O.sub.2] alone. However, only rhSOD restored eNOS function, increased tetrahydrobiopterin ([BH.sub.4]), a critical cofactor for eNOS function, and restored GTP cyclohydrolase I expression in isolated vessels and lungs from PPHN lambs. These data suggest that ventilation of PPHN lambs with 100% [O.sub.2] increases ROS production, blunts postnatal increases in eNOS expression, and decreases available [BH.sub.4] in PPHN lambs. Although the addition of iNO or rhSOD diminished ROS production and increased eNOS expression, only rhSOD improved eNOS function and levels of available [BH.sub.4]. Thus therapies designed to decrease oxidative stress and restore eNOS coupling, such as rhSOD, may prove useful in the treatment of PPHN in newborn infants. reactive oxygen species; biopterin

Byline: Jean Dellamonica (1,2,3), Bruno Louis (2,4), Aissam Lyazidi (1,2), Frederic Vargas (1,2), Laurent Brochard (1,2,4) Abstract: Objective Intrapulmonary percussive ventilation (IPV) is a form of high-frequency ventilation that can be superimposed on spontaneous breathing or conventional ventilation. Drawbacks include difficulties achieving adequate airway humidification and an inability to monitor delivered volumes and pressures, which may vary with patient characteristics. The objectives of this study were to assess various humidification set-ups, to measure intrapulmonary pressures and volumes resulting from IPV superimposed on a conventional driving ventilator (DV) and to test several ventilators regarding their ability to accept added IPV. Design Bench study in a test-lung set-up was used to measure humidification and the effects of adding IPV to a DV under various conditions of compliance, resistance, plateau and positive end-expiratory pressures. Then, five ventilators were tested in combination with IPV. Measurements and results Adequate humidification required a heated humidifier on the inspiratory line downstream of the IPV device. IPV increased end-inspiratory intrapulmonary pressures up to 10 cm[H.sub.2]O, increased delivered volumes up to 237 ml and generated intrinsic PEEP from 1.7 to 4.3 cm[H.sub.2]O when no PEEP was set on the DV. Intrinsic PEEP was lower or absent when PEEP was set on the DV. With most tested ventilators, IPV prevented reliable flow monitoring. Autotriggering and missing cycles were common and the PEEP effect varied across DVs. Conclusion Achieving adequate humidification with IPV requires a specific set-up. Superimposing IPV on standard ventilation can increase intrapulmonary pressures and tidal volumes importantly and interfere with the triggering sensors of the ventilator. These factors must be taken into account before clinical use. Author Affiliation: (1) Reanimation Medicale, AP-HP, Centre Hospitalier Albert Chenevier, Henri Mondor, Creteil, France (2) INSERM U 841, Creteil, France (3) Reanimation Medicale, CHU de Nice Hopital L'Archet, Nice Cedex, France (4) Universite Paris 12, Creteil, France Article History: Registration Date: 11/06/2008 Received Date: 20/10/2007 Accepted Date: 26/05/2008 Online Date: 01/07/2008 Article note: Electronic supplementary material The online version of this article (doi: 10.1007/s00134-008-1190-9) contains supplementary material, which is available to authorized users.

Byline: Evelina Sturini (1,4), Andrea Saporito (1), Michael Sugrue (2), Michael J. A. Parr (1), Gillian Bishop (1), Antonio Braschi (3) Keywords: Intra-abdominal pressure; Respiratory variation; Mechanical ventilation; Intra-abdominal hypertension; Abdominal compliance; Intensive care unit Abstract: Objective To assess if the observed respiratory cycle-related variation in intra-abdominal pressure is reliably quantifiable and a possible indirect indicator of abdominal compliance. Secondary issues were to assess the roles played by respiratory parameters in determining this oscillation and by patients' position in increasing their intra-abdominal pressure. Design and setting Prospective observational study in a 26-bed medical-surgical intensive care unit. Patients Sixteen consecutive patients admitted to intensive care for at least 24 h, requiring mechanical ventilation and intra-abdominal pressure monitoring. Measurements and results Intra-abdominal pressure was measured with a modified Kron technique its waveform was recorded and inspiratory and expiratory values were measured during five consecutive respiratory cycles for 5 days, both in the supine and the 30deg head-up position. Inspiratory values were significantly higher than expiratory values (p = 0.001) and a correlation was found between their difference and intra-abdominal pressure basal values (p = 0.025). A positive linear relationship was shown between intra-abdominal pressure and the amplitude of its oscillation (r = 0.4), particularly in the subgroup of patients with intra-abdominal hypertension (r = 0.9). Intra-abdominal pressure was lower in patients supine than in the 30deg head-up position (p = 0.001). Conclusions Respiratory cycle-related variations in intra-abdominal pressure were specifically investigated, quantified and shown as linearly increasing with end-expiratory intra-abdominal pressure this phenomenon could be explained by patients' abdominal compliance status. Supine posture should be an important consideration in specific patients affected by intra-abdominal hypertension. Author Affiliation: (1) Intensive Care Unit, Liverpool Hospital, University of New South Wales, Elizabeth St, Liverpool, Sydney, NSW, 1871, Australia (2) Trauma Department, Liverpool Hospital, University of New South Wales, Elizabeth St, Liverpool, Sydney, NSW, 1871, Australia (3) Cattedra di Anestesia e Rianimazione, Universita degli Studi di Pavia, IRCCS Policlinico San Matteo, P.zzale Golgi 2, 27100, Pavia, Italy (4) via 26 Aprile 2, 27040, Verrua Po, PV, Italy Article History: Registration Date: 08/05/2008 Received Date: 11/09/2007 Accepted Date: 06/05/2008 Online Date: 24/05/2008

Byline: Michel E. Berner (1), Sylviane Hanquinet (2), Peter C. Rimensberger (3) Keywords: Respiratory syncytial virus; High frequency oscillatory ventilation; Bronchiolitis; Respiratory failure; Hypercapnia Abstract: Objective To describe the time course of high frequency oscillatory ventilation (HFOV) in respiratory syncytial virus (RSV) bronchiolitis. Design Retrospective charts review. Setting A tertiary paediatric intensive care unit. Patients and participants Infants with respiratory failure due to RSV infection. Intervention HFOV. Measurements and results Pattern of lung disease, ventilatory settings, blood gases, infant's vital parameters, sedation and analgesia during the periods of conventional mechanical ventilation (CMV, 6 infants), after initiation of HFOV (HFOVi, 9 infants), in the middle of its course (HFOVm), at the end (HFOVe) and after extubation (Post-Extub) were compared. All infants showed a predominant overexpanded lung pattern. Mean airway pressure was raised from a mean (SD) 12.5 (2.0) during CMV to 18.9 (2.7) cm[H.sub.2]O during HFOVi (P < 0.05), then decreased to 11.1(1.3) at HFOVe (P < 0.05). Mean FiO.sub.2 was reduced from 0.68 (0.18) (CMV) to 0.59 (0.14) (HFOVi) then to 0.29 (0.06) (P < 0.05) at HFOVe and mean peak to peak pressure from 44.9 (12.4) cm[H.sub.2]O (HFOVi) to 21.1 (7.7) P < 0.05 (HFOVe) while mean (SD) PaCO.sub.2 showed a trend to decrease from 72 (22) (CMV) to 47 (8) mmHg (HFVOe) and mean infants respiratory rate a trend to increase from 20 (11) (HFOVi) to 34 (14) (HFOVe) breaths/min. With usual doses of sedatives and opiates, no infant was paralysed and all were extubated to CPAP or supplemental oxygen after a mean of 120 h. Conclusion RSV induced respiratory failure with hypercapnia can be managed with HFOV using high mean airway pressure and large pressure swings while preserving spontaneous breathing. Author Affiliation: (1) Neonatology and Paediatric Intensive Care Service, Geneva University Hospitals and University of Geneva, Geneva, Switzerland (2) Paediatric Radiology Unit, Geneva University Hospitals and University of Geneva, Geneva, Switzerland (3) Neonatology and Paediatric Intensive Care Service, Geneva University Hospitals and University of Geneva, Geneva, Switzerland Article History: Registration Date: 07/05/2008 Received Date: 21/06/2007 Accepted Date: 06/12/2007 Online Date: 24/05/2008 Article note: This article is discussed in the editorial available at doi: 10.1007/s00134-008-1152-2.

Byline: Etienne Javouhey (1), Audrey Barats (2), Nathalie Richard (1), Didier Stamm (1), Daniel Floret (1) Keywords: Bronchiolitis; Non-invasive ventilation; Pulmonary infection; Children; Duration of ventilation Abstract: Objective To report our experience of non-invasive ventilation (NIV) as primary ventilatory support strategy in infants admitted for severe bronchiolitis. Design and setting Retrospective study in a paediatric intensive care unit of an university hospital. Patients Infants aged less than 12 months, admitted for bronchiolitis during 2003--2004 and 2004--2005 winter epidemics. Intervention NIV was used as the primary ventilatory support during the second winter (NIV period), whereas invasive ventilation (IV) was the only support employed during the first winter (IV period). NIV consisted in either continuous positive airway pressure (CPAP from 5 to 10 cm[H.sub.2]O) or bilevel positive airway pressure (inspiratory pressure from 12 to 18 cm[H.sub.2]O) with a nasal mask. Results During the IV period, 53 infants were included, compared to 27 during the NIV period. The two groups did not differ in age or in number of premature births. Children in NIV group had less apnoea on admission. The intubation rate was reduced during NIV period (p < 0.001). No children had ventilator-associated pneumonia (VAP) during NIV period compared to nine during IV period (p < 0.05). In the NIV group, 10 infants (37%) required supplemental oxygen for more than 8 days compared to 33 children (65%) in IV group (p < 0.05). The length of hospital stay and the duration of ventilation were similar. Conclusions In this retrospective study, the use of NIV decreased the rate of ventilator associated pneumonia and reduced the duration of oxygen requirement without prolonging the hospital stay. Author Affiliation: (1) Service de Reanimation Pediatrique Hopital Femme Mere Enfant, Groupement Hospitalier Est, 59 Boulevard Pinel, Hospices Civils de Lyon, Universite Lyon 1, 69677, Bron Cedex, France (2) Service de pediatrie 2, Hopital Hautepierre, avenue Moliere, 67200, Strasbourg, France Article History: Registration Date: 07/05/2008 Received Date: 02/03/2007 Accepted Date: 22/12/2007 Online Date: 24/05/2008 Article note: This article is discussed in the editorial available at: doi: 10.1007/s00134-008-1152-2. This work was accepted for a poster presentation in the XXXIVdeg congres de la Societe de Reanimation de Langue Francaise (SRLF). Paris-la Defense, 18--20 janvier 2006 (Reanimation vol 14, suppl 1, SP126) and for an oral presentation in the 8th European Conference in Paediatric and Neonatal Ventilation, 29 Mars--01 Avril 2006, Montreux, Switzerland. Electronic supplementary material The online version of this article (doi: 10.1007/s00134-008-1150-4) contains supplementary material, which is available to authorized users.

Byline: Juliana C. Ferreira (1,2), Daniel W. Chipman (3), Robert M. Kacmarek (3,4) Keywords: Ventilators; Mechanical; Respiratory mechanics; Respiration; Artificial; Intensive care units; Equipment safety; Models; Biological Abstract: Objective To compare the triggering performance of mid-level ICU mechanical ventilators with a standard ICU mechanical ventilator. Design Experimental bench study. Setting The respiratory care laboratory of a university-affiliated teaching hospital. Subject A computerized mechanical lung model, the IngMar ASL5000. Interventions Ten mid-level ICU ventilators were compared to an ICU ventilator at two levels of lung model effort, three combinations of respiratory mechanics (normal, COPD and ARDS) and two modes of ventilation, volume and pressure assist/control. A total of 12 conditions were compared. Measurements and main results Performance varied widely among ventilators. Mean inspiratory trigger time was Conclusions Triggering differences among these mid-level ICU ventilators and with the ICU ventilator were identified. Some of these ventilators had a much poorer triggering response with high inspiratory effort than the ICU ventilator. These ventilators do not perform as well as ICU ventilators in patients with high ventilatory demand. Author Affiliation: (1) Departments of Respiratory Care and Anesthesia and Critical Care, Massachusetts General Hospital, Boston, MA, USA (2) Pulmonary Division, Respiratory ICU, Hospital das Clinicas, University of Sao Paulo, Sao Paulo, Brazil (3) Respiratory Care Services--Ellison 401, Massachusetts General Hospital, 55 Fruit Street, Boston, MA, 02114, USA (4) Department of Anesthesia, Harvard Medical School, Boston, MA, USA Article History: Registration Date: 11/04/2008 Received Date: 19/07/2007 Accepted Date: 04/04/2008 Online Date: 30/04/2008 Article note: This study was partially funded by an unrestricted grant from Hamilton Medical Dr. Ferreira was partially funded by CAPES, Brazil. Robert Kacmarek has received research grants and honorariums for lecturing from Hamilton Medical, Puritan-Bennett Corp, Respironics Inc. Viasys Inc and Maquet Medical and is a consultant for Space Labs. Daniel Chipman has received honorarium from Maquet Medical for lecturing.

Byline: J.-O. Neumann (1), I. R. Chambers (2), G. Citerio (3), P. Enblad (4), B. A. Gregson (5), T. Howells (4), J. Mattern (1), P. Nilsson (4), I. Piper (6), A. Ragauskas (7), J. Sahuquillo (8), Y. H. Yau (9), K. Kiening (1) Keywords: Traumatic brain injury; Hyperventilation Abstract: Objective To assess the use of hyperventilation and the adherence to Brain Trauma Foundation-Guidelines (BTF-G) after traumatic brain injury (TBI). Setting Twenty-two European centers are participating in the BrainIT initiative. Design Retrospective analysis of monitoring data. Patients and participants One hundred and fifty-one patients with a known time of trauma and at least one recorded arterial blood--gas (ABG) analysis. Measurements and results A total number of 7,703 ABGs, representing 2,269 ventilation episodes (VE) were included in the analysis. Related minute-by-minute ICP data were taken from a 30 min time window around each ABG collection. Data are given as mean with standard deviation. (1) Patients without elevated intracranial pressure (ICP) ( Conclusion While overall adherence to current BTF-G seems to be the rule, its recommendations on early prophylactic hyperventilation as well as the use of additional cerebral oxygenation monitoring during forced hyperventilation are not followed in this sample of European TBI centers. Descriptor Neurotrauma Author Affiliation: (1) Department of Neurosurgery, Universitatsklinikum Heidelberg, Im Neuenheimer Feld 400, 69120, Heidelberg, Germany (2) Regional Medical Physics Department, James Cook University Hospital, Middlesborough, UK (3) Department of Perioperative Medicine and Intensive Care, NeuroICU, Hospital San Gerardo, Monza, Italy (4) Department of Clinical Neurosciences, Section of Neurosurgery, Uppsala University Hospital, Uppsala, Sweden (5) Department of Neurosurgery, Newcastle General Hospital, Newcastle upon Tyne, UK (6) Department of Clinical Physics, Institute of Neurological Sciences, Southern General Hospital, Glasgow, Scotland (7) Telematics Science Laboratory, Kaunas University of Technology, Kaunas, Lithuania (8) Department of Neurosurgery, Neurotraumatology Research Unit, Vall d'Hebron University Hospital, Barcelona, Spain (9) Department of Neurosurgery, Western General Hospital, Edinburgh, Scotland Article History: Registration Date: 11/04/2008 Received Date: 29/07/2007 Accepted Date: 01/04/2008 Online Date: 01/05/2008

Byline: Rafael Fernandez (1), Xavier Trenchs (2), Jordi Klamburg (3), Jon Castedo (4), Jose Manuel Serrano (5), Guillermo Besso (6), Juan Pedro Tirapu (7), Antonio Santos (8), Arantxa Mas (9), Manuel Parraga (10), Paola Jubert (11), Fernando Frutos (12), Jose Manuel Anon (13), Manuela Garcia (14), Fernando Rodriguez (15), Joan Carles Yebenes (16), Maria Jesus Lopez (17) Keywords: Prone positioning; Mechanical ventilation; Acute respiratory distress syndrome; Randomized controlled trial; Survival; Acute lung injury Abstract: Objective We examined the effect on survival of prone positioning as an early and continuous treatment in ARDS patients already treated with protective ventilation. Design and setting Open randomized controlled trial in 17 medical-surgical ICUs. Patients Forty mechanically ventilated patients with early and refractory ARDS despite protective ventilation in the supine position. Interventions Patients were randomized to remain supine or be moved to early (within 48a-h) and continuous (aY=a-20a-h/day) prone position until recovery or death. The trial was prematurely stopped due to a low patient recruitment rate. Measurements and results Clinical characteristics, oxygenation, lung pressures, and hemodynamics were monitored. Need for sedation, complications, length of MV, ICU, and hospital stays, and outcome were recorded. PaO.sub.2/FIO.sub.2 tended to be higher in prone than in supine patients after 6a-h (202a-+-a-78 vs. 165a-+-a-70a-mmHg) this difference reached statistical significance on day 3 (234a-+-a-85 vs. 159a-+-a-78). Prone-related side effects were minimal and reversible. Sixty-day survival reached the targeted 15% absolute increase in prone patients (62% vs. 47%) but failed to reach significance due to the small sample. Conclusions Our study adds data that reinforce the suggestion of a beneficial effect of early continuous prone positioning on survival in ARDS patients. Author Affiliation: (1) CIBER Enfermedades Respiratorias, ICU, Hospital de Sabadell, Parc Taulis/n, 08208, Sabadell, Spain (2) ICU, Hospital de Terrassa, Terrassa, Spain (3) ICU, Hospital Germans Trias i Pujol, Badalona, Spain (4) ICU, University Hospital De Canarias, La Laguna, Spain (5) ICU, Hospital Reina Sofia, Cordoba, Spain (6) ICU, Hospital Carlos Haya, Malaga, Spain (7) ICU, Hospital de Navarra, Pamplona, Spain (8) ICU, Complexo University Hospital, Santiago de Compostela, Spain (9) ICU, Fundacion Althaia, Manresa, Spain (10) ICU, Hospital Morales Messeguer, Murcia, Spain (11) ICU, Hospital Santa Tecla, Tarragona, Spain (12) ICU, Hospital Universitario, Getafe, Spain (13) ICU, Hospital Virgen de la Luz, Cuenca, Spain (14) ICU, Hospital Virgen Macarena, Sevilla, Spain (15) ICU, Clinica San Miguel, Pamplona, Spain (16) ICU, Hospital de Mataro, Mataro, Spain (17) ICU, Hospital General Yague, Burgos, Spain Article History: Registration Date: 27/03/2008 Received Date: 07/01/2008 Accepted Date: 14/03/2008 Online Date: 22/04/2008 Article note: Electronic supplementary material The online version of this article (doi: 10.1007/s00134-008-1119-3) contains supplementary material, which is available to authorized users.

Byline: Francesco Mojoli (1,2), Giorgio A. Iotti (3), Maddalena Gerletti (1), Carlo Lucarini (1), Antonio Braschi (1,2) Keywords: Non-invasive ventilation; Helmet; Carbon dioxide; Rebreathing; Monitoring; Physical model Abstract: Objective To define how to monitor and limit CO.sub.2 rebreathing during helmet ventilation. Design Physical model study. Setting Laboratory in a university teaching hospital. Interventions We applied pressure-control ventilation to a helmet mounted on a physical model. In series 1 we increased CO.sub.2 production (V'CO.sub.2) from 100 to 550a-ml/min and compared mean inhaled CO.sub.2 (iCO.sub.2,mean) with end-inspiratory CO.sub.2 at airway opening (eiCO.sub.2), end-tidal CO.sub.2 at Y-piece (yCO.sub.2) and mean CO.sub.2 inside the helmet (hCO.sub.2). In series 2 we observed, at constant V'CO.sub.2, effects on CO.sub.2 rebreathing of inspiratory pressure, respiratory mechanics, the inflation of cushions inside the helmet and the addition of a flow-by. Measurements and results In series 1, iCO.sub.2,mean linearly related to V'CO.sub.2. The best estimate of CO.sub.2 rebreathing was provided by hCO.sub.2: differences between iCO.sub.2,mean and hCO.sub.2, yCO.sub.2 and eiCO.sub.2 were 0.0a-+-a-0.1, 0.4a-+-a-0.2 and -1.3a-+-a-0.5%. In series 2, hCO.sub.2 inversely related to the total ventilation (MVtotal) delivered to the helmet--patient unit. The increase in inspiratory pressure significantly increased MVtotal and lowered hCO.sub.2. The low lung compliance halved the patient:helmet ventilation ratio but led to minor changes in MVtotal and hCO.sub.2. Cushion inflation, although it decreased the helmet's internal volume by 33%, did not affect rebreathing. A 8-l/min flow-by effectively decreased hCO.sub.2. Conclusions During helmet ventilation, rebreathing can be assessed by measuring hCO.sub.2 or yCO.sub.2, but not eiCO.sub.2. It is directly related to V'CO.sub.2, inversely related to MVtotal and can be lowered by increasing inspiratory pressure or adding a flow-by. Author Affiliation: (1) Servizio di Anestesia e Rianimazione I, Fondazione IRCCS Policlinico S. Matteo, Piazzale Golgi 2, Pavia, Italy (2) Cattedra di Anestesiologia e Rianimazione, Universita degli Studi di Pavia, Pavia, Italy (3) Servizio di Anestesia e Rianimazione II, Fondazione IRCCS Policlinico S. Matteo, Pavia, Italy Article History: Registration Date: 25/03/2008 Received Date: 06/11/2007 Accepted Date: 15/03/2008 Online Date: 18/04/2008

For disease states characterized by oscillatory ventilation, an ideal dynamic therapy would apply a counteracting oscillation in ventilation. Modulating respiratory gas transport through the circulation might allow this. We explore the ability of repetitive alternations in heart rate, using a cardiac pacemaker, to elicit oscillations in respiratory variables and discuss the potential for therapeutic exploitation. By incorporating acute cardiac output manipulations into an integrated mathematical model, we observed that a rise in cardiac output should yield a gradual rise in end-tidal C[O.sub.2] and, subsequently, ventilation. An alternating pattern of cardiac output might, therefore, create oscillations in C[O.sub.2] and ventilation. We studied the effect of repeated alternations in heart rate of 30 beats/rain with periodicity of 60 s, on cardiac output, respiratory gases, and ventilation in 22 subjects with implanted cardiac pacemakers and stable breathing patterns. End-tidal C[O.sub.2] and ventilation developed consistent oscillations with a period of 60 s during the heart rate alternations, with mean peak-to-trough relative excursions of 8.4 [+ or -] 5.0% (P < 0.0001) and 24.4 [+ or -] 18.8% (P < 0.0001), respectively. Furthermore, we verified the mathematical prediction that the amplitude of these oscillations would depend on those in cardiac output (r = 0.59, P = 0.001). Repetitive alternations in heart rate can elicit reproducible oscillations in end-tidal C[O.sub.2] and ventilation. The size of this effect depends on the magnitude of the cardiac output response. Harnessed and timed appropriately, this cardiorespiratory mechanism might be exploited to create an active dynamic responsive pacing algorithm to counteract spontaneous respiratory oscillations, such as those causing apneic breathing disorders. periodic breathing; physiology; pacing; reflex