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Clinical Investigations

Effects of Mechanical Ventilation on Release of Cytokines into Systemic Circulation in Patients with Normal Pulmonary Function

Wrigge, Hermann M.D.*; Zinserling, Jörg M.Sc.†; Stüber, Frank M.D.‡; von Spiegel, Tilman M.D.§; Hering, Rudolf M.D.∥; Wetegrove, Silke M.D.#; Hoeft, Andreas M.D.**; Putensen, Christian M.D.††

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Background: Mechanical ventilation with high tidal volumes (VT) in contrast to mechanical ventilation with low VT has been shown to increase plasma levels of proinflammatory and antiinflammatory mediators in patients with acute lung injury. The authors hypothesized that, in patients without previous lung injury, a conventional potentially injurious ventilatory strategy with high VT and zero end-expiratory pressure (ZEEP) will not cause a cytokine release into systemic circulation.
Methods: A total of 39 patients with American Society of Anesthesiologists physical status I–II and without signs of systemic infection scheduled for elective surgery with general anesthesia were randomized to receive mechanical ventilation with either (1) VT = 15 ml/kg ideal body weight on ZEEP, (2) VT = 6 ml/kg ideal body weight on ZEEP, or (3) VT = 6 ml/kg ideal body weight on positive end-expiratory pressure of 10 cm H2O. Plasma levels of proinflammatory and antiinflammatory mediators tumor necrosis factor, interleukin (IL)-6, IL-10, and IL-1 receptor antagonist were determined before and 1 h after the initiation of mechanical ventilation.
Results: Plasma levels of all cytokines remained low in all settings. IL-6, tumor necrosis factor, and IL-1 receptor antagonist did not change significantly after 1 h of mechanical ventilation. IL-10 was below the detection limit (10 pg/ml) in 35 of 39 patients. There were no differences between groups.
Conclusions: Initiation of mechanical ventilation for 1 h in patients without previous lung injury caused no consistent changes in plasma levels of studied mediators. Mechanical ventilation with high VT on ZEEP did not result in higher cytokine levels compared with lung-protective ventilatory strategies. Previous lunge damage seems to be mandatory to cause an increase in plasma cytokines after 1 h of high VT mechanical ventilation.
POSITIVE pressure ventilation is commonly applied in patients undergoing general anesthesia to assure adequate ventilation and gas exchange. Conventional mechanical ventilation still uses low positive end-expiratory pressure (PEEP) levels with high tidal volumes (VT) ranging between 10 and 15 ml/kg ideal body weight. 1–4 However, positive pressure ventilation alone or in combination with preexisting lung disease may contribute considerably to lung injury, including pneumothorax, alveolar edema, and alveolar rupture. 5,6
Mechanical ventilation with PEEP titrated above the lower inflection pressure of a static pressure–volume curve and low VT has been suggested to prevent tidal collapse and overdistension of lung regions during severe acute respiratory distress syndrome (ARDS). 7 This lung-protective ventilatory strategy has been shown to improve gas exchange and outcome in patients with ARDS. 8 Recently, Ranieri et al.9 observed higher systemic and intraalveolar levels of proinflammatory cytokines in ARDS patients during mechanical ventilation with low PEEP and high VT when compared with a lung-protective strategy. Therefore, it has been speculated that conventional mechanical ventilation may induce release of inflammatory mediators and thereby contribute to lung injury. 10In vitro experiments have demonstrated that mechanical stress to lung cells is associated with release of inflammatory mediators. 11,12 However, acute lung injury or ARDS itself causes an inflammation of the lungs with increased systemic and intraalveolar concentrations of the proinflammatory cytokines. 13 It is unclear whether mechanical ventilation alone or only in the presence of acute lung injury can release inflammatory cytokines into systemic circulation.
We hypothesized that, in patients with normal lungs, mechanical ventilation with high VT does not induce a release of cytokines into the systemic circulation. To test this hypothesis, we measured proinflammatory and antiinflammatory cytokines in the plasma of anesthetized patients with healthy lungs while they were mechanically ventilated with lung-protective or conventional strategies.
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Materials and Methods

Approval of the Bonn University Ethics Committee, Bonn, Germany, for the study protocol was obtained, and all patients gave written informed consent before inclusion in the study.
Table 1
Table 1
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Thirty-nine adult patients classified as American Society of Anesthesiologists physical status I or II scheduled for elective extrathoracic surgery with general anesthesia (table 1) were eligible to participate in the study. 14 Patients with history or clinical signs of lung disease, history of smoking, age older than 65 yr, immunosuppression by drugs or underlying condition, elevated leukocyte count, or clinical signs of a systemic infection were not included in the study.
All patients received a standard premedication of 7.5 mg midazolam orally on the day of surgery. Anesthesia was induced using thiopental (4–6 mg/kg administered intravenously) and fentanyl (1–2 μg/kg administered intravenously). Thereafter, cis-atracurium (0.10–0.15 mg/kg administered intravenously) was given to facilitate tracheal intubation. Mechanical ventilation was provided with an anesthesia ventilator connected to a circle system (Julian, Dräger, Lübeck, Germany) with a fresh gas flow of air–oxygen at 4 l/min and an inspiratory fraction of oxygen of 0.30. Anesthesia was maintained with 0.5 minimum alveolar concentration of isoflurane and supplemental doses of fentanyl as required. Routine perioperative monitoring included measurement of noninvasive blood pressure, pulse oximetry, and electrocardiogram (CS/3, Datex-Ohmeda, Helsinki, Finland). End-tidal fractions of carbon dioxide and isoflurane were measured using infrared absorption capnography (Julian, Dräger). All patients received infusion of 1.5 l of crystalloid fluids during the study period to assure hemodynamic stability.
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Ventilatory Measurements
Gas flow was measured at the proximal end of the tracheal tube with a heated pneumotachograph (No. 2; Fleisch, Lausanne, Switzerland) connected to a differential pressure transducer (Huba Control, Würenlos, Switzerland). Airway pressure was measured at the proximal end of the tracheal tube with another differential gas–pressure transducer (SMT, Munich, Germany). All signals were sampled with an analog–digital converter board (PCM-DAS16S/12, Mansfield, MA) installed in a personal computer. Digitized signals were plotted in real time on the computer screen and stored on magnetic media for offline analysis. VT and minute ventilation were derived from the integrated gas flow signal.
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Cytokine Measurements
Venous EDTA blood samples of 5 ml were centrifuged at 1,500 g for 5 min, and the plasma was aspirated and stored at −70°C. Commercially available enzyme-linked immunosorbent assays were used to measure plasma levels of interleukin (IL)-6, tumor necrosis factor (TNF) (Biosource, Ratingen, Germany), IL-10, and IL-1 receptor antagonist (R&D Systems, Minneapolis, MN). All enzyme-linked immunosorbent assay analyses were performed with strict adherence to the manufacturers’ guidelines.
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All patients remained supine throughout the study period. Baseline measurements were obtained immediately before induction of anesthesia.
After induction of anesthesia, patients were randomly assigned to receive either mechanical ventilation with VT of 15 ml/kg ideal body weight and zero end-expiratory pressure (ZEEP) (high VT, ZEEP group), a VT of 6 ml/kg ideal body weight and ZEEP (low VT, ZEEP group), or a VT of 6 ml/kg ideal body weight and 10 cm H2O PEEP (low VT, PEEP group). The ventilator rate was adjusted to maintain end-tidal carbon dioxide partial pressure between 35 and 45 mmHg. After ventilation with the assigned mode was stable for 1 h, the measurements were repeated. Thereafter, data collection was concluded and the surgical procedure was allowed to commence.
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To detect differences in cytokine plasma levels between the ventilatory settings with the given two-sided parallel design at a significance level of 5% (α = 0.05) with a probability of 80% (β = 0.20) based on an estimated difference of 0.85 of the parameter’s mean SD, a minimum of 39 patients were to be studied.
Results are expressed as mean ± SD. All statistical analysis were performed using a statistical software package (Statistica for Windows 5.1, StatSoft, Inc., Tulsa, OK). Data were tested for normal distribution with the Sharpiro-Wilks W test. Ventilatory variables were analyzed using a one-way analysis of variance. When a significant F ratio was obtained, differences between the means were isolated with the post hoc Tukey multiple comparison test. Because cytokine data were not normally distributed, a two-way analysis of variance was performed after log10 transformation to permit the application of a parametric test. Differences were considered to be statistically significant at P values less than 0.05.
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There were no statistically significant differences in the demographic or clinical data between patients of the studied groups (table 1).
Table 2
Table 2
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Ventilatory variables are shown in table 2. During mechanical ventilation with low VT, a higher ventilator rate (P < 0.001) and a higher minute ventilation (P < 0.001) were required to achieve the desired end-tidal carbon dioxide partial pressure range, compared with high VT mechanical ventilation. Increase in ventilatory rate was associated with a reduction of inspiratory time and expiratory time (P < 0.05), whereas the inspiratory time/expiratory time ratio remained unchanged. Peak airway pressure was lowest during mechanical ventilation with low VT at ZEEP. In the presence of PEEP, mechanical ventilation with low VT resulted in the highest mean airway pressure. End-tidal carbon dioxide partial pressure was lowest during mechanical ventilation with high VT at ZEEP.
Fig. 1
Fig. 1
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Fig. 2
Fig. 2
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Fig. 3
Fig. 3
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Cytokine plasma levels are shown in figures 1–3. The response of the cytokine levels to starting mechanical ventilation was neither significantly different between the three ventilatory strategies nor statistically different after 1 h of ventilation in each individual group. Plasma levels of IL-10 remained below the detection limit (10 pg/ml) in 35 of 39 patients both at baseline and after 1 h of mechanical ventilation.
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This study was designed to evaluate the effects of different ventilatory strategies on the release of inflammatory mediators into the systemic circulation of anesthetized patients who had healthy lungs. We were unable to detect statistically significant differences in cytokine release between potentially injurious and protective ventilatory strategies after 1 h of ventilation.
Mechanical ventilation is usually provided by using low PEEP levels with high VT ranging between 10 and 15 ml/kg ideal body weight. 1–4 Based on experimental data, mechanical ventilation with high VT has been claimed to overdistend functional lung units and contribute to direct lung damage. 6 Mechanical stress such as shear stress has been found to induce production of inflammatory cytokines in isolated endothelial, 15 epithelial, 16 and macrophage cells. 17 Experimental and clinical studies have investigated the production of inflammatory mediators in injured lungs induced by various ventilatory strategies. 9,11,12,17–20 Based on these findings, inflammatory cytokines have been implicated as contributors to ventilator-associated lung injury. 21 A recent multicenter trial of 861 patients demonstrated a reduction in mortality by 22% and lower systemic cytokine levels when VT was reduced from 12 to 6 ml/kg ideal body weight. 22
We studied the effect of different ventilatory strategies on systemic cytokine levels during anesthesia before elective surgery. Although our patients had an essentially normal pulmonary function, previous computed tomography studies have clearly demonstrated alveolar collapse and atelectasis soon after induction of anesthesia and mechanical ventilation in previously healthy patients, 23,24 which can be prevented with a PEEP of 10 cm H2O. 25 Thus, the lung-protective ventilatory settings in this study should have prevented tidal alveolar collapse and overdistension, whereas the potentially injurious ventilatory should have not. 23 The latter has been suggested to result in shear forces with transmural pressures of up to 100 cm H2O applied to lung cells. 26
In our patients, we did not observe consistent differences in proinflammatory and antiinflammatory cytokine plasma levels depending on different ventilatory strategies, and all levels were still within the variability observed in healthy volunteers. 27 Therefore, our findings appear to be in contrast with previous experimental 12 and clinical 9,28 observations, indicating a marked systemic inflammatory response in the presence of an injurious ventilatory strategy using low PEEP and high VT. Variation in the systemic cytokine concentrations observed during injurious mechanical ventilation may be attributed to the difference in the design and the experimental conditions of the individual studies. Tremblay et al.12 found pronounced production of cytokines induced by injurious mechanical ventilation in animals pretreated with intravenous lipopolysaccharides, 12 whereas pressure stretching of cultivated alveolar macrophages in absence of lipopolysaccharides as an inflammatory costimulus could not induce TNF and IL-6 excretion. 17 These findings support our observation that mechanical ventilation seems to induce no inflammation in normal lungs, but may well augment lung inflammation to clinically important levels in preinjured or infected lungs. In agreement with our findings, in rats without lung injury, mechanical ventilation with VT set at 10 ml/kg did not affect bronchoalveolar lavage fluid content of IL-1α, IL-1β, IL-6, macrophage inflammatory protein-2, and TNF when compared with spontaneous breathing, 19 whereas in a rat model with hydrochloric acid instillation–induced lung injury, mechanical ventilation with VT of 16 ml and ZEEP resulted in a marked increase in TNF and macrophage inflammatory protein-2 when compared with VT of 9 ml and PEEP of 5 cm H2O. 11
Unfortunately, we cannot draw conclusions on lung tissue cytokine concentrations on the basis of plasma cytokine levels. Previous studies suggest that an increase in alveolar–capillary permeability is required for translocation of mediators, including cytokines, from the lungs into the circulation. 29,30 Because inflammatory mediators cause an increase in vascular and alveolar permeability, a relevant accumulation of cytokines in the lungs should have resulted in an increased release of cytokines into the blood and alveolar fluid.
It is also important to note that we tested each ventilatory strategy only for 1 h. Experimental data have demonstrated that intraalveolar expression of TNF gene 31 and increased TNF levels in the systemic circulation 11 can be found after 1 h of injurious mechanical ventilation in lung injury models. Preliminary clinical data in patients with injured lungs indicate that maximal increase in alveolar and systemic cytokine concentrations occurs within 1 h after initiating mechanical ventilation with low PEEP and high VT. 28 Therefore, the lack of an increase in plasma cytokines during injurious mechanical ventilation in our patients should not be attributed to a time-related component on the cytokine release. However, we did not study long-term effects of mechanical ventilation on cytokine production in healthy lungs or the effects of mechanical ventilation combined with a surgical intervention, which itself may cause an inflammatory response or even bacteremia.
General anesthesia itself has been suggested to modulate the inflammatory response during mechanical ventilation. 32 Recent experimental data suggest that inflammatory response to mechanical ventilation may be aggravated by inhalation of volatile anesthetics after 2 h. 19 Studies comparing the immune response to standardized elective surgery in patients during propofol versus isoflurane anesthesia have revealed no differences 33 or a minimally diminished systemic inflammatory response with propofol and alfentanil when compared with isoflurane and nitrous oxide anesthesia. 34 Anesthesia in all of our patients was provided with isoflurane and fentanyl. Therefore, it is unlikely that anesthesia has a major influence on our results after a study period of only 1 h.
Our data suggest that in essentially normal lungs of anesthetized patients, short-term mechanical ventilation with high VT in the presence or absence of PEEP induces no clinical relevant increase in systemic proinflammatory and antiinflammatory cytokines. This observation is indirect evidence that mechanical ventilation seems to induce no inflammation in normal lungs, but may well augment lung inflammation to clinically important levels in preinjured or infected lungs as previously shown.
The authors are grateful to Alexandra Casalter, Department of Anesthesiology and Intensive Care Medicine, Uinversity of Bonn, Bonn, Germany, for technical laboratory assistance, and Jukka Räsänen, M.D., Department of Anesthesiology, Mayo Clinic, Rochester, Minnesota, for careful critique of the manuscript.
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Production of endothelin-1 and reduced blood flow in the rat kidney during lung-injurious mechanical ventilation
Kuiper, JW; Versteilen, AMG; Niessen, HWM; Vaschetto, RR; Sipkema, P; Heijnen, CJ; Groeneveld, ABJ; Plotz, FB
Anesthesia and Analgesia, 107(4): 1276-1283.
Acta Anaesthesiologica Scandinavica
Airway closure in anesthetized infants and children: influence of inspiratory pressures and volumes
Thorsteinsson, A; Werner, O; Jonmarker, C; Larsson, A
Acta Anaesthesiologica Scandinavica, 46(5): 529-536.

Intensive Care Medicine
Kinetic and reversibility of mechanical ventilation-associated pulmonary and systemic inflammatory response in patients with acute lung injury
Stuber, F; Wrigge, H; Schroeder, S; Wetegrove, S; Zinserling, J; Hoeft, A; Putensen, C
Intensive Care Medicine, 28(7): 834-841.
Vascular Pharmacology
Effect of different ventilatory strategies on local and systemic cytokine production in intact swine lungs in vivo
Myrianthefs, P; Boutzouka, E; Venetsanou, K; Papalois, A; Kouloukousa, M; Kittas, C; Baltopoulos, G
Vascular Pharmacology, 44(5): 283-289.
Journal of Pediatrics
Mechanical Ventilation of Newborns Infant Changes in Plasma Pro- and Anti-Inflammatory Cytokines
Bohrer, B; Silveira, RC; Neto, EC; Procianoy, RS
Journal of Pediatrics, 156(1): 16-19.
Anesthesia and Analgesia
Low Tidal Volume and High Positive End-Expiratory Pressure Mechanical Ventilation Results in Increased Inflammation and Ventilator-Associated Lung Injury in Normal Lungs
Hong, CM; Xu, DZ; Lu, Q; Cheng, YHI; Pisarenko, V; Doucet, D; Brown, M; Aisner, S; Zhang, CX; Deitch, EA; Delphin, E
Anesthesia and Analgesia, 110(6): 1652-1660.
Anesthesia and Analgesia
The effects of different ventilatory settings on pulmonary and systemic inflammatory responses during major surgery
Wrigge, H; Uhlig, U; Zinserling, J; Behrends-Callsen, E; Ottersbach, G; Fischer, M; Uhlig, S; Putensen, C
Anesthesia and Analgesia, 98(3): 775-781.

American Journal of Respiratory and Critical Care Medicine
Atelectasis causes vascular leak and lethal right ventricular failure in uninjured rat lungs
Duggan, M; McCaul, CL; McNamara, PJ; Engelberts, D; Ackerley, C; Kavanagh, BP
American Journal of Respiratory and Critical Care Medicine, 167(): 1633-1640.
Minerva Anestesiologica
Lung protective ventilation in ARDS: the open lung maneuver
Haitsma, JJ; Lachmann, B
Minerva Anestesiologica, 72(3): 117-132.

Clinical Physiology and Functional Imaging
Lung protective ventilatory strategies in acute lung injury and acute respiratory distress syndrome: from experimental findings to clinical application
Verbrugge, SJC; Lachmann, B; Kesecioglu, J
Clinical Physiology and Functional Imaging, 27(2): 67-90.
Medical Science Monitor
Lung-protective mechanical ventilation with lower tidal volumes in patients not suffering from acute lung injury: A review of clinical studies
Schultz, MJ
Medical Science Monitor, 14(2): RA22-RA26.

Modulatory effects of hypercapnia on in vitro and in vivo pulmonary endothelial-neutrophil adhesive responses during inflammation
Liu, YL; Chacko, BK; Ricksecker, A; Shingarev, R; Andrews, E; Patel, RP; Lang, JD
Cytokine, 44(1): 108-117.
Anasthesiologie & Intensivmedizin
Risks and benefits of mechanical ventilation with positive end-expiratory pressure during the perioperative phase
Neumann, P; Klockgether-Radke, A; Quintel, M
Anasthesiologie & Intensivmedizin, 45(3): 137-146.

Anesthesia and Analgesia
The pulmonary immune effects of mechanical ventilation in patients undergoing thoracic surgery
Schilling, T; Kozian, A; Huth, C; Buhling, F; Kretzschmar, M; Welte, T; Hachenberg, T
Anesthesia and Analgesia, 101(4): 957-965.
Respiratory Care
Should tidal volume be 6 mL/kg predicted body weight in virtually all patients with acute respiratory failure? Discussion
MacIntyre; Kacmarek; Rubin; Cheifetz; Steinberg; Hurford; Pierson
Respiratory Care, 52(5): 565-567.

Anesthesia and Analgesia
Pulmonary cytokine responses during mechanical ventilation of noninjured lungs with and without end-expiratory pressure
Meier, T; Lange, A; Papenberg, H; Ziemann, M; Fentrop, C; Uhlig, U; Schmucker, P; Uhlig, S; Stamme, C
Anesthesia and Analgesia, 107(4): 1265-1275.
Clinical Physiology and Functional Imaging
Injurious ventilation strategies cause systemic release IL-6 and MIP-2 in rats in vivo
Haitsma, JJ; Uhlig, S; Verbrugge, SJ; Goggel, R; Poelma, DLH; Lachmann, B
Clinical Physiology and Functional Imaging, 23(6): 349-353.

Journal of Applied Physiology
Vascular endothelial growth factor and related molecules in acute lung injury
Mura, M; dos Santos, CC; Stewart, D; Liu, MY
Journal of Applied Physiology, 97(5): 1605-1617.
Journal of Anesthesia
Hyperventilation versus standard ventilation for infants in postoperative care for congenital heart defects with pulmonary hypertension
Umenai, T; Shime, N; Hashimoto, S
Journal of Anesthesia, 23(1): 80-86.
Anesthesia and Analgesia
One-lung ventilation with high tidal volumes and zero positive end-expiratory pressure is injurious in the isolated rabbit lung model
de Abreu, MG; Heintz, M; Heller, A; Szechenyi, R; Albrecht, DM; Koch, T
Anesthesia and Analgesia, 96(1): 220-228.
British Journal of Anaesthesia
Lung injury after thoracotomy
Baudouin, SV
British Journal of Anaesthesia, 91(1): 132-142.
Intensive Care Medicine
Effects of protective and conventional mechanical ventilation on pulmonary function and systemic cytokine release after cardiopulmonary bypass
Koner, O; Celebi, S; Balci, H; Cetin, G; Karaoglu, K; Cakar, N
Intensive Care Medicine, 30(4): 620-626.
Acta Anaesthesiologica Scandinavica
Effects of sevoflurane and desflurane on cytokine response during tympanoplasty surgery
Koksal, GM; Sayilgan, C; Gungor, G; Oz, H; Sen, O; Uzun, H; Aydin, S
Acta Anaesthesiologica Scandinavica, 49(6): 835-839.
Netherlands Journal of Medicine
Cytokines and biotrauma in ventilator-induced lung injury: a critical review of the literature
Halbertsma, FJJ; Vaneker, M; Scheffer, GJ; van der Hoeven, JG
Netherlands Journal of Medicine, 63(): 382-392.

Surgical Clinics of North America
Basic ventilator management: Lung protective strategies
Donahoe, M
Surgical Clinics of North America, 86(6): 1389-+.
Experimental Lung Research
Elevated Endogenous Surfactant Reduces Inflammation in An Acute Lung Injury Model
Walker, MG; Tessolini, JM; McCaig, L; Yao, LJ; Lewis, JF; Veldhuizen, RAW
Experimental Lung Research, 35(7): 591-604.
Intensive Care Medicine
Low tidal volume ventilation induces proinflammatory and profibrogenic response in lungs of rats
Caruso, P; Meireles, SI; Reis, LFL; Mauad, T; Martins, MA; Deheinzelin, D
Intensive Care Medicine, 29(): 1808-1811.
Intensive Care Medicine
Prophylactic protective ventilation: lower tidal volumes for all critically ill patients?
Lellouche, F; Lipes, J
Intensive Care Medicine, 39(1): 6-15.
Critical Care
Lower tidal volume at initiation of mechanical ventilation may reduce progression to acute respiratory distress syndrome: a systematic review
Fuller, BM; Mohr, NM; Drewry, AM; Carpenter, CR
Critical Care, 17(1): -.
British Journal of Anaesthesia
Tidal volume measurement: OK for science, but too difficult for a workstation standard?
Scott, DHT; Drummond, GB
British Journal of Anaesthesia, 110(6): 891-895.
Mechanical Ventilation with Lower Tidal Volumes and Positive End-expiratory Pressure Prevents Pulmonary Inflammation in Patients without Preexisting Lung Injury
Wolthuis, EK; Choi, G; Dessing, MC; Bresser, P; Lutter, R; Schultz, MJ; Dzoljic, M; van der Poll, T; Vroom, MB; Hollmann, M
Anesthesiology, 108(1): 46-54.
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Inhibition of Poly(Adenosine Diphosphate–Ribose) Polymerase Attenuates Ventilator-induced Lung Injury
Vaschetto, R; Kuiper, JW; Chiang, SR; Haitsma, JJ; Juco, JW; Uhlig, S; Plötz, FB; Corte, FD; Zhang, H; Slutsky, AS
Anesthesiology, 108(2): 261-268.
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Adaptive Support Ventilation: An Inappropriate Mechanical Ventilation Strategy for Acute Respiratory Distress Syndrome?
Sulemanji, D; Kacmarek, R
Anesthesiology, 112(5): 1295-1296.
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What Tidal Volumes Should Be Used in Patients without Acute Lung Injury?
Schultz, MJ; Haitsma, JJ; Slutsky, AS; Gajic, O
Anesthesiology, 106(6): 1226-1231.
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Effect of Mechanical Ventilation on Cytokine Response to Intratracheal Lipopolysaccharide
Whitehead, TC; Zhang, H; Mullen, B; Slutsky, AS
Anesthesiology, 101(1): 52-58.

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Mechanical Ventilation in Healthy Mice Induces Reversible Pulmonary and Systemic Cytokine Elevation with Preserved Alveolar Integrity: An In Vivo Model Using Clinical Relevant Ventilation Settings
Snijdelaar, DG; Joosten, LA; van der Hoeven, JG; Scheffer, GJ; Vaneker, M; Halbertsma, FJ; van Egmond, J; Netea, MG; Dijkman, HB
Anesthesiology, 107(3): 419-426.
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Mechanical Ventilation: Taking Its Toll on the Lung
Curley, GF; Kevin, LG; Laffey, JG
Anesthesiology, 111(4): 701-703.
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Protective Ventilation Influences Systemic Inflammation after Esophagectomy: A Randomized Controlled Study
Michelet, P; D’Journo, X; Roch, A; Doddoli, C; Marin, V; Papazian, L; Decamps, I; Bregeon, F; Thomas, P; Auffray, J
Anesthesiology, 105(5): 911-919.

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Conventional Mechanical Ventilation Is Associated with Bronchoalveolar Lavage-induced Activation of Polymorphonuclear Leukocytes: A Possible Mechanism to Explain the Systemic Consequences of Ventilator-induced Lung Injury in Patients with ARDS
Zhang, H; Downey, GP; Suter, PM; Slutsky, AS; Ranieri, VM
Anesthesiology, 97(6): 1426-1433.

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Critical Care Medicine
Ventilatory and hemodynamic management of potential organ donors: An observational survey*
Mascia, L; Bosma, K; Pasero, D; Galli, T; Cortese, G; Donadio, P; Bosco, R
Critical Care Medicine, 34(2): 321-327.
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Critical Care Medicine
Gas exchange of lung-protective ventilation strategies in pigs with normal lungs
Meybohm, P; Scholz, J; Weiler, N; Bein, B
Critical Care Medicine, 35(5): 1447.
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Critical Care Medicine
Gas exchange of lung-protective ventilation strategies in pigs with normal lungs
Roosens, C; Poelaert, J
Critical Care Medicine, 35(5): 1448.
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Critical Care Medicine
Mechanical ventilation and acute renal failure*
Kuiper, JW; Groeneveld, AB; Slutsky, AS; Plötz, FB
Critical Care Medicine, 33(6): 1408-1415.
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Critical Care Medicine
Hemodynamic effects of different lung-protective ventilation strategies in closed-chest pigs with normal lungs
Roosens, CD; Ama, R; Leather, HA; Segers, P; Sorbara, C; Wouters, PF; Poelaert, JI
Critical Care Medicine, 34(12): 2990-2996.
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Current Opinion in Anesthesiology
Acute lung injury and outcomes after thoracic surgery
Licker, M; Fauconnet, P; Villiger, Y; Tschopp, J
Current Opinion in Anesthesiology, 22(1): 61-67.
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Current Opinion in Critical Care
Extracellular matrix and mechanical ventilation in healthy lungs: back to baro/volotrauma?
Pelosi, P; Negrini, D
Current Opinion in Critical Care, 14(1): 16-21.
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Current Opinion in Critical Care
Delirium: acute cognitive dysfunction in the critically ill
Pandharipande, P; Jackson, J; Ely, EW
Current Opinion in Critical Care, 11(4): 360-368.

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Current Opinion in Critical Care
Assessing neurocognitive outcomes after critical illness: are delirium and long-term cognitive impairments related?
Hopkins, RO; Jackson, JC
Current Opinion in Critical Care, 12(5): 388-394.
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Neonatal respiratory failure
Rimensberger, PC
Current Opinion in Pediatrics, 14(3): 315-321.

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European Journal of Anaesthesiology (EJA)
The effects of sevoflurane and desflurane on lipid peroxidation during laparoscopic cholecystectomy
Koksal, GM; Sayilgan, C; Aydin, S; Uzun, H; Oz, H
European Journal of Anaesthesiology (EJA), 21(3): 217-220.

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European Journal of Anaesthesiology (EJA)
Study of the systemic and pulmonary oxidative stress status during exposure to propofol and sevoflurane anaesthesia during thoracic surgery: Retracted
Abou-Elenain, K
European Journal of Anaesthesiology (EJA), 27(6): 566-571.
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European Journal of Anaesthesiology (EJA)
Role of Toll‐like receptor 4 for the pathogenesis of acute lung injury in Gram‐negative sepsis
Fink, K; Meyer, R; Hoeft, A; Grohé, C; Baumgarten, G; Knuefermann, P; Wrigge, H; Putensen, C; Stapel, H
European Journal of Anaesthesiology (EJA), 23(12): 1041-1048.
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Recombinant Human Soluble Tumor Necrosis Factor-Alpha Receptor Fusion Protein Partly Attenuates Ventilator-Induced Lung Injury
Wolthuis, EK; Vlaar, AP; Choi, G; Roelofs, JJ; Haitsma, JJ; van der Poll, T; Juffermans, NP; Zweers, MM; Schultz, MJ
Shock, 31(3): 262-266.
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Lin, S; Lin, H; Lee, K; Huang, C; Liu, C; Wang, C; Kuo, H
Shock, 28(4): 453-460.
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Back to Top | Article Outline
Inflammation; lung; mediators; ventilator-associated lung injury.

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