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For many years, mechanical ventilation with high tidal volumes ( V T ) was common practice in operating theaters because this strategy recruits collapsed lung tissue, improves ventilation–perfusion mismatch, and thus decreases the need for high oxygen fractions. Positive end-expiratory pressure (PEEP) was seldom used because it could cause cardiac compromise. Increasing advances in the understanding of the mechanisms of ventilator-induced lung injury from animal studies and randomized controlled trials in patients with uninjured lungs in intensive care unit and operation room have pushed anesthesiologists to consider lung-protective strategies during intraoperative ventilation. These strategies at least include the use of low V T , and perhaps also the use of PEEP, which when compared to high V T with low PEEP may prevent the occurrence of postoperative pulmonary complications (PPCs). Such protective effects, however, are likely ascribed to low V T rather than to PEEP. In fact, at least in nonobese patients undergoing open abdominal surgery, high PEEP does not protect against PPCs, and it can impair the hemodynamics. Further studies shall determine whether a strategy consisting of low V T combined with PEEP and recruitment maneuvers reduces PPCs in obese patients and other types of surgery (e.g., laparoscopic and thoracic), compared to low V T with low PEEP. Furthermore, the role of driving pressure for titrating ventilation settings in patients with uninjured lungs shall be investigated.

Postoperative pulmonary complications are associated with increased morbidity, length of hospital stay, and mortality after major surgery. Intraoperative lung-protective mechanical ventilation has the potential to reduce the incidence of postoperative pulmonary complications. This review discusses the relevant literature on definition and methods to predict the occurrence of postoperative pulmonary complication, the pathophysiology of ventilator-induced lung injury with emphasis on the noninjured lung, and protective ventilation strategies, including the respective roles of tidal volumes, positive end-expiratory pressure, and recruitment maneuvers. The authors propose an algorithm for protective intraoperative mechanical ventilation based on evidence from recent randomized controlled trials.

Purpose of review To summarize clinical evidence for intraoperative ventilation settings, which could protect against postoperative pulmonary complications (PPCs) in surgical patients with uninjured lungs. Recent findings There is convincing evidence for protection against PPCs by low tidal volumes: benefit was found in several randomized controlled trials, and was recently confirmed in meta-analyses. Evidence for protection against PPCs by high levels of positive end-expiratory pressure (PEEP) is less definite. Although benefit was found in several randomized controlled trials, most of them compared a bundle of low tidal volume and high level of PEEP with conventional ventilation; one recent large randomized controlled trial that compared high with low levels of PEEP showed that ventilation with high level of PEEP did not protect against PPCs but caused intraoperative complications instead. A recent individual patient data meta-analysis of trials comparing bundles of low tidal volume and high levels of PEEP to conventional intraoperative ventilation suggested that protection against PPCs comes from tidal volume reductions, and not from increasing levels of PEEP. Summary The understanding on the protective roles of tidal volume and PEEP settings against PPCs has rapidly expanded. During intraoperative ventilation, low tidal volumes are protective, the protective role of high levels of PEEP is uncertain

Background: Recent studies show that intraoperative mechanical ventilation using low tidal volumes (VT) can prevent postoperative pulmonary complications (PPCs). The aim of this individual patient data meta-analysis is to evaluate the individual associations between VT size and positive end–expiratory pressure (PEEP) level and occurrence of PPC. Methods: Randomized controlled trials comparing protective ventilation (low VT with or without high levels of PEEP) and conventional ventilation (high VT with low PEEP) in patients undergoing general surgery. The primary outcome was development of PPC. Predefined prognostic factors were tested using multivariate logistic regression. Results: Fifteen randomized controlled trials were included (2,127 patients). There were 97 cases of PPC in 1,118 patients (8.7%) assigned to protective ventilation and 148 cases in 1,009 patients (14.7%) assigned to conventional ventilation (adjusted relative risk, 0.64; 95% CI, 0.46 to 0.88; P < 0.01). There were 85 cases of PPC in 957 patients (8.9%) assigned to ventilation with low VT and high PEEP levels and 63 cases in 525 patients (12%) assigned to ventilation with low VT and low PEEP levels (adjusted relative risk, 0.93; 95% CI, 0.64 to 1.37; P = 0.72). A dose–response relationship was found between the appearance of PPC and VT size (R2 = 0.39) but not between the appearance of PPC and PEEP level (R2 = 0.08). Conclusions: These data support the beneficial effects of ventilation with use of low VT in patients undergoing surgery. Further trials are necessary to define the role of intraoperative higher PEEP to prevent PPC during nonopen abdominal surgery.

Lung injury is a serious complication of surgery. We did a systematic review and meta-analysis to assess whether incidence, morbidity, and in-hospital mortality associated with postoperative lung injury are affected by type of surgery and whether outcomes are dependent on type of ventilation. We searched MEDLINE, CINAHL, Web of Science, and Cochrane Central Register of Controlled Trials for observational studies and randomised controlled trials published up to April, 2014, comparing lung-protective mechanical ventilation with conventional mechanical ventilation during abdominal or thoracic surgery in adults. Individual patients' data were assessed. Attributable mortality was calculated by subtracting the in-hospital mortality of patients without postoperative lung injury from that of patients with postoperative lung injury. We identified 12 investigations involving 3365 patients. The total incidence of postoperative lung injury was similar for abdominal and thoracic surgery (3·4% vs 4·3%, p=0·198). Patients who developed postoperative lung injury were older, had higher American Society of Anesthesiology scores and prevalence of sepsis or pneumonia, more frequently had received blood transfusions during surgery, and received ventilation with higher tidal volumes, lower positive end-expiratory pressure levels, or both, than patients who did not. Patients with postoperative lung injury spent longer in intensive care (8·0 [SD 12·4] vs 1·1 [3·7] days, p

To assess the effects of different levels of spontaneous breathing during biphasic positive airway pressure/airway pressure release ventilation on lung function and injury in an experimental model of moderate acute respiratory distress syndrome.Multiple-arm randomized experimental study.University hospital research facility.Thirty-six juvenile pigs.Pigs were anesthetized, intubated, and mechanically ventilated. Moderate acute respiratory distress syndrome was induced by repetitive saline lung lavage. Biphasic positive airway pressure/airway pressure release ventilation was conducted using the airway pressure release ventilation mode with an inspiratory/expiratory ratio of 1:1. Animals were randomly assigned to one of four levels of spontaneous breath in total minute ventilation (n = 9 per group, 6 hr each): 1) biphasic positive airway pressure/airway pressure release ventilation, 0%; 2) biphasic positive airway pressure/airway pressure release ventilation,0-30%; 3) biphasic positive airway pressure/airway pressure release ventilation,30-60%, and 4) biphasic positive airway pressure/airway pressure release ventilation,60%.The inspiratory effort measured by the esophageal pressure time product increased proportionally to the amount of spontaneous breath and was accompanied by improvements in oxygenation and respiratory system elastance. Compared with biphasic positive airway pressure/airway pressure release ventilation of 0%, biphasic positive airway pressure/airway pressure release ventilation more than 60% resulted in lowest venous admixture, as well as peak and mean airway and transpulmonary pressures, redistributed ventilation to dependent lung regions, reduced the cumulative diffuse alveolar damage score across lungs (median [interquartile range], 11 [3-40] vs 18 [2-69]; p0.05), and decreased the level of tumor necrosis factor-α in ventral lung tissue (median [interquartile range], 17.7 pg/mg [8.4-19.8] vs 34.5 pg/mg [29.9-42.7]; p0.05). Biphasic positive airway pressure/airway pressure release ventilation more than 0-30% and more than 30-60% showed a less consistent pattern of improvement in lung function, inflammation, and damage compared with biphasic positive airway pressure/airway pressure release ventilation more than 60%.In this model of moderate acute respiratory distress syndrome in pigs, biphasic positive airway pressure/airway pressure release ventilation with levels of spontaneous breath higher than usually seen in clinical practice, that is, more than 30% of total minute ventilation, reduced lung injury with improved respiratory function, as compared with protective controlled mechanical ventilation.

In experimental elastase-induced emphysema, mechanical ventilation with variable tidal volumes (VT) set to 30% coefficient of variation (CV) may result in more homogenous ventilation distribution, but might also impair right heart function. We hypothesized that a different CV setting could improve both lung and cardiovascular function. Therefore, we investigated the effects of different levels of VT variability on cardiorespiratory function, lung histology, and gene expression of biomarkers associated with inflammation, fibrogenesis, epithelial cell damage, and mechanical cell stress in this emphysema model. Wistar rats (n = 35) received repeated intratracheal instillation of porcine pancreatic elastase to induce emphysema. Seven animals were not ventilated and served as controls (NV). Twenty-eight animals were anesthetized and assigned to mechanical ventilation with a VT CV of 0% (BASELINE). After data collection, animals (n = 7/group) were randomly allocated to VT CVs of 0% (VV0); 15% (VV15); 22.5% (VV22.5); or 30% (VV30). In all groups, mean VT was 6 mL/kg and positive end-expiratory pressure was 3 cmH2O. Respiratory system mechanics and cardiac function (by echocardiography) were assessed continuously for 2 h (END). Lung histology and molecular biology were measured post-mortem. VV22.5 and VV30 decreased respiratory system elastance, while VV15 had no effect. VV0, VV15, and VV22.5, but not VV30, increased pulmonary acceleration time to pulmonary ejection time ratio. VV22.5 decreased the central moment of the mean linear intercept (D2 of Lm) while increasing the homogeneity index (1/β) compared to NV (77 ± 8 μm vs. 152 ± 45 μm; 0.85 ± 0.06 vs. 0.66 ± 0.13, p < 0.05 for both). Compared to NV, VV30 was associated with higher interleukin-6 expression. Cytokine-induced neutrophil chemoattractant-1 expression was higher in all groups, except VV22.5, compared to NV. IL-1β expression was lower in VV22.5 and VV30 compared to VV0. IL-10 expression was higher in VV22.5 than NV. Club cell protein 16 expression was higher in VV22.5 than VV0. SP-D expression was higher in VV30 than NV, while SP-C was higher in VV30 and VV22.5 than VV0. In conclusion, VV22.5 improved respiratory system elastance and homogeneity of airspace enlargement, mitigated inflammation and epithelial cell damage, while avoiding impairment of right cardiac function in experimental elastase-induced emphysema.

Intraoperative mechanical ventilation may yield lung injury. To date, there is no consensus regarding the best ventilator strategy for abdominal surgery. We aimed to investigate the impact of the mechanical ventilation strategies used in 2 recent trials (Intraoperative Protective Ventilation [IMPROVE] trial and Protective Ventilation using High versus Low PEEP [PROVHILO] trial) on driving pressure (ΔPRS), mechanical power, and lung damage in a model of open abdominal surgery. Thirty-five Wistar rats were used, of which 28 were anesthetized, and a laparotomy was performed with standardized bowel manipulation. Postoperatively, animals (n = 7/group) were randomly assigned to 4 hours of ventilation with: (1) tidal volume (VT) = 7 mL/kg and positive end-expiratory pressure (PEEP) = 1 cm H2O without recruitment maneuvers (RMs) (low VT/low PEEP/RM-), mimicking the low-VT/low-PEEP strategy of PROVHILO; (2) VT = 7 mL/kg and PEEP = 3 cm H2O with RMs before laparotomy and hourly thereafter (low VT/moderate PEEP/4 RM+), mimicking the protective ventilation strategy of IMPROVE; (3) VT = 7 mL/kg and PEEP = 6 cm H2O with RMs only before laparotomy (low VT/high PEEP/1 RM+), mimicking the strategy used after intubation and before extubation in PROVHILO; or (4) VT = 14 mL/kg and PEEP = 1 cm H2O without RMs (high VT/low PEEP/RM-), mimicking conventional ventilation used in IMPROVE. Seven rats were not tracheotomized, operated, or mechanically ventilated, and constituted the healthy nonoperated and nonventilated controls. Low VT/moderate PEEP/4 RM+ and low VT/high PEEP/1 RM+, compared to low VT/low PEEP/RM- and high VT/low PEEP/RM-, resulted in lower ΔPRS (7.1 ± 0.8 and 10.2 ± 2.1 cm H2O vs 13.9 ± 0.9 and 16.9 ± 0.8 cm H2O, respectively; P

Background Invasive mechanical ventilation during general anaesthesia for surgery typically causes atelectasis and impairs postoperative lung function. Objective We investigated the effect of intraoperative ventilation with high positive end-expiratory pressure (PEEP) and recruitment manoeuvres (RMs) on postoperative spirometry. Design This was a preplanned, single-centre substudy of an international multicentre randomised controlled trial, the PROVHILO trial. Setting University hospital from November 2011 to January 2013. Patients Nonobese patients scheduled for major abdominal surgery at a high risk of postoperative pulmonary complications (PPCs). Intervention Intraoperative low tidal volume ventilation with PEEP levels of 12 cmH2O and RM (the high PEEP group) or with PEEP levels of 2 cmH2O or less without RM (the low PEEP group). Main outcome measures Time-weighted averages (TWAs) of the forced expiratory volume in 1 s (FEV1) and the forced vital capacity (FVC) up to postoperative day five. Results Thirty-one patients were allocated to the high PEEP group and 32 to the low PEEP group. No postoperative spirometry test results were available for 6 patients. In both groups, TWA of FEV1 and FVC until postoperative day five were lower than preoperative values. Postoperative spirometry test results were not different between the high and low PEEP group; Data are median [interquartile range], TWA FVC 1.8 [1.6 to 2.4] versus 1.7 [1.2 to 2.4] l (P = NS) and TWA FEV1 1.2 [1.1 to 2.5] versus 1.2 [0.9 to 1.9] l (P = NS). Patients who developed PPCs had lower FEV1 and FVC on postoperative day five; 1.1 [0.9 to 1.6] versus 1.6 [1.4 to 1.9] l (P = 0.001) and 1.6 [1.2 to 2.6] versus 2.3 [1.7 to 2.6] l (P = 0.036), respectively. Conclusion Postoperative spirometry is not affected by PEEP and RM during intraoperative ventilation for open abdominal surgery in nonobese patients at a high risk of PPCs, but rather is associated with the development of PPCs. Trial registration ClinicalTrials.gov NCT01441791.

Background: Fluid resuscitation is the cornerstone in treatment of shock, and intravenous fluid administration is the most frequent intervention in operation rooms and intensive care units (ICUs). The composition of fluids used for fluid resuscitation gained interest over the past decade, with recent focus on whether balanced solutions should be preferred over isotonic saline. Methods: Systematic review and meta-analysis of randomized controlled trials (RCTs) comparing fluid resuscitation with a balanced solution versus isotonic saline in adult patients in operation room or ICUs. Primary outcome was in-hospital mortality, secondary outcomes included occurrence of acute kidney injury (AKI) and need for renal replacement therapy (RRT). Results: The search identified 11 RCTs involving 2,703 patients; 8 trials were conducted in operation room and 3 in ICU. In-hospital mortality, as well as the occurrence of AKI and need for RRT was not different between resuscitation with balanced solutions versus isotonic saline, neither in operation room nor in ICU patients. Serum chloride levels, but not arterial pH, were significantly lower in patients resuscitated with balanced solutions. Conclusions: Currently evidence insufficiently supports the use of balanced over isotonic saline for fluid resuscitation to improve outcome of operation room and ICU patients.

Background Quantitative lung computed tomography (CT) provides fundamental information about lung aeration in critically ill patients. We tested a scanning protocol combining reduced number of CT slices and tube current, comparing quantitative analysis and radiation exposure to conventional CT. Methods In pigs, CT scans were performed during breath hold in a model of lung injury with three different protocols: standard spiral with 180 mAs tube current-time product (Spiral180), sequential with 20-mm distance between slices and either 180 mAs (Sequential180) or 50 mAs (Sequential50). Spiral scans of critically ill patients were collected retrospectively, and subsets of equally spaced slices were extracted. The agreement between CT protocols was assessed with Bland–Altman analysis. Results In 12 pigs, there was good concordance between the sequential protocols and the spiral scan (all biases ≤1.9%, agreements ≤±6.5%). In Spiral180, Sequential180 and Sequential50, estimated dose exposure was 2.3 (2.1–2.8), 0.21 (0.19–0.26), and 0.09 (0.07–0.10) mSv, respectively (p

Intra-abdominal hypertension (IAH) may co-occur with the acute respiratory distress syndrome (ARDS), with significant impact on morbidity and mortality. Lung-protective controlled mechanical ventilation with low tidal volume and positive end-expiratory pressure (PEEP) has been recommended in ARDS. However, mechanical ventilation with spontaneous breathing activity may be beneficial to lung function and reduce lung damage in mild ARDS. We hypothesized that preserving spontaneous breathing activity during pressure support ventilation (PSV) would improve respiratory function and minimize ventilator-induced lung injury (VILI) compared to pressure-controlled ventilation (PCV) in mild extrapulmonary acute lung injury (ALI) with IAH. Thirty Wistar rats (334±55g) received Escherichia coli lipopolysaccharide intraperitoneally (1000μg) to induce mild extrapulmonary ALI. After 24h, animals were anesthetized and randomized to receive PCV or PSV. They were then further randomized into subgroups without or with IAH (15 mmHg) and ventilated with PCV or PSV (PEEP = 5cmH2O, driving pressure adjusted to achieve tidal volume = 6mL/kg) for 1h. Six of the 30 rats were used for molecular biology analysis and were not mechanically ventilated. The main outcome was the effect of PCV versus PSV on mRNA expression of interleukin (IL)-6 in lung tissue. Regardless of whether IAH was present, PSV resulted in lower mean airway pressure (with no differences in peak airway or peak and mean transpulmonary pressures) and less mRNA expression of biomarkers associated with lung inflammation (IL-6) and fibrogenesis (type III procollagen) than PCV. In the presence of IAH, PSV improved oxygenation; decreased alveolar collapse, interstitial edema, and diffuse alveolar damage; and increased expression of surfactant protein B as compared to PCV. In this experimental model of mild extrapulmonary ALI associated with IAH, PSV compared to PCV improved lung function and morphology and reduced type 2 epithelial cell damage.

Lung ischemia-reperfusion injury remains a major complication after lung transplantation. Variable ventilation (VV) has been shown to improve respiratory function and reduce pulmonary histological damage compared to protective volume-controlled ventilation (VCV) in different models of lung injury induced by endotoxin, surfactant depletion by saline lavage, and hydrochloric acid. However, no study has compared the biological impact of VV versus VCV in lung ischemia-reperfusion injury, which has a complex pathophysiology different from that of other experimental models. Thirty-six animals were randomly assigned to one of two groups: 1) ischemia-reperfusion (IR), in which the left pulmonary hilum was completely occluded and released after 30 min; and 2) Sham, in which animals underwent the same surgical manipulation but without hilar clamping. Immediately after surgery, the left (IR-injured) and right (contralateral) lungs from 6 animals per group were removed, and served as non-ventilated group (NV) for molecular biology analysis. IR and Sham groups were further randomized to one of two ventilation strategies: VCV (n = 6/group) [tidal volume (VT) = 6 mL/kg, positive end-expiratory pressure (PEEP) = 2 cmH2O, fraction of inspired oxygen (FiO2) = 0.4]; or VV, which was applied on a breath-to-breath basis as a sequence of randomly generated VT values (n = 1200; mean VT = 6 mL/kg), with a 30% coefficient of variation. After 5 minutes of ventilation and at the end of a 2-hour period (Final), respiratory system mechanics and arterial blood gases were measured. At Final, lungs were removed for histological and molecular biology analyses. Respiratory system elastance and alveolar collapse were lower in VCV than VV (mean ± SD, VCV 3.6 ± 1.3 cmH20/ml and 2.0 ± 0.8 cmH20/ml, p=0.005; median [interquartile range], VCV 20.4% [7.9-33.1] and VV 5.4% [3.1-8.8], p=0.04, respectively). In left lungs of IR animals, VCV increased the expression of interleukin-6 and intercellular adhesion molecule-1 compared to NV, with no significant differences between VV and NV. Compared to VCV, VV increased the expression of surfactant protein-D, suggesting protection from type II epithelial cell damage. In conclusion, in this experimental lung ischemia-reperfusion model, VV improved respiratory system elastance and reduced lung damage compared to VCV.

Thoracic surgery is frequently accompanied by postoperative pulmonary complications (PPCs). PPCs may be mild, moderate, or severe complications and increase the length of stay in hospital and even mortality. Notably, the chance of developing PPCs may be associated with specific intraoperative risk factors, as identified in retrospective, observational prospective, single- and multiple-center studies. Such factors may be combined and weighed in scores that might be useful to predict the risk of developing PPCs. Some of those scores allow identifying subpopulations with especially high risk of adverse postoperative pulmonary events, but they may differ in their performance. Despite those differences, PPCs after thoracic surgery can be predicted with acceptable sensitivity and specificity and may be useful for selecting high-risk groups, planning interventions, and allocating resources.

Mechanical ventilation has the potential to increase inflammation in both healthy and injured lungs. Several animal studies have shown that variable ventilation recruits the lungs and reduces inflammation. However, it is unclear which cellular mechanisms are involved in those findings. We hypothesized that variable stretch of LPS-stimulated alveolar epithelial cells (AECs) reduces the production of pro-inflammatory cytokines compared to non-variable stretch. AECs were subjected to non-variable or variable cyclic stretch (sinusoidal pattern), with and without LPS stimulation. The expression and release of interleukin-6, CXCL-2 and CCL-2 mRNA were analyzed after 4 hours. The phosphorylation of the MAPKs ERK1/2 and SAPK/JNK was determined by Western Blot analysis at 0, 15, 30, 45 and 60 min of cyclic stretch. In LPS-stimulated AECs, variable cyclic cell stretching led to reduced cytokine expression and release compared to non-variable cell stretching. Furthermore, the phosphorylation of the MAPK ERK1/2 was increased after 30 minutes in non-variable stretched AECs, whereas variable stretched cells demonstrated only the non-stretched level of phosphorylation. After the 4h period of cyclic cell stretch and inhibition of the ERK1/2, but not the SAPK/JNK, signaling pathway, the gene expression of investigated cytokines increased in variable stretched, and decreased in non-variable stretched AECs. We conclude that in LPS-stimulated AECs, variable stretch reduced the pro-inflammatory response compared to non-variable stretch. This effect was mediated by the ERK1/2 signaling pathway, and might partly explain the findings of reduced lung inflammation during mechanical ventilation modes that enhance breath-by-breath variability of the respiratory pattern.

This study aimed to develop and evaluate an adaptive control system for volume-controlled ventilation (VCV) in small animals to guarantee accurate delivery of tidal volume (VT) in the presence of changes in lung mechanics.The adaptive control system to control the Harvard Inspira ventilator was designed and evaluated on a custom-made physical model during step changes of resistance and elastance of the respiratory system assessing difference in minute ventilation (ΔMVc) during convergence cycles (NC). The controller was then evaluated during conventional and variable volume VCV in rats with acute respiratory distress syndrome (ARDS) induced by intratracheal HCl (six animals/group), where the difference between desired and applied VT (dVT,d), its root-mean square error (RMSE) and relative deviation from target minute ventilation (ΔMV) were determined.The controller showed fast convergence NC20 cycles with an acceptable ΔMVC10% in simulations and nearly abolished dVT,d (VCV: 0.23 ± 0.1 mL to 0.0 ± 0.0 mL, P.001 and vVCV: 0.05 ± 0.8 mL to 0.0 ± 0.0 mL, P.001), significantly reduced RMSE (VCV: 0.23 ± 0.1 to 0.04 ± 0.01 mL, P.001 and vVCV: 0.13 ± 0.04 to 0.08 ± 0.02 mL, P.001) and ΔMV (VCV: 11.6 ± 4.2 to 0.04 ± 0.15%, P.001 and vVCV: -3 ± 3.8 to -0.35 ± 1.3 %, P.001) in animal experiments. In VCV the improvement was more pronounced, due to reduced respiratory system elastance in this group (VCV: 5.6 cmH2O mL(-1) versus vVCV: 3.8 cmH2O mL(-1), P.001).The new adaptive controller ensured accurate delivery of VT in VCV and proved valuable for mechanical ventilation of small animals especially in ARDS research.

This review summarizes the most recent clinical and experimental data on the impact of spontaneous breathing in acute respiratory distress syndrome (ARDS).Spontaneous breathing during assisted as well as nonassisted modes of mechanical ventilation improves lung function and reduces lung damage in mild and moderate ARDS. New modes of assisted mechanical ventilation with improved patient ventilator interaction and enhanced variability of the respiratory pattern offer additional benefit on lung function and damage. However, data supporting an outcome benefit of spontaneous breathing in ARDS, even in its mild and moderate forms, are missing. In contrast, controlled mechanical ventilation with muscle paralysis in the first 48 h of severe ARDS has been shown to improve survival, as compared with placebo. Currently, it is unclear whether ventilator settings, rather than the severity of lung injury, determine the potential of spontaneous breathing for benefit or harm.Clinical and experimental studies show that controlled mechanical ventilation with muscle paralysis in the early phase of severe ARDS reduces lung injury and even mortality. At present, spontaneous breathing should be avoided in the early phase of severe ARDS, but considered in mild-to-moderate ARDS.

Made available in DSpace on 2018-12-11T17:23:15Z (GMT). No. of bitstreams: 0 Previous issue date: 2016-11-01 Hospital Sírio Libanês Sociedade de Anestesiologia do Estado de São Paulo (Saesp) Sociedade Brasileira de Anestesiologia (SBA) Yale University School of Medicine Hospital de Transplantes do Estado de São Paulo – Euryclides de Jesus Zerbini Hospital Israelita Albert Einstein Hospital Moriah University of Chicago Northwestern School of Medicine Instituto do Coração do Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo (INCOR/HCFMUSP) Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo (HCFMUSP) Instituto do Câncer do Estado de São Paulo (ICESP) Hospital do Servidor Público Estadual (HSPE) Faculdade de Medicina de São José do Rio Preto (Famerp) Hospital de Base de São José do Rio Preto Faculdade de Medicina da Universidade de São Paulo (FMUSP) Disciplina de Emergências Clínicas Instituto de Ensino e Pesquisa do Hospital Sírio Libanês Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo (HCFMUSP) Unidade de Terapia Intensiva A. C. Camargo Cancer Center University Hospital Carl Gustav Carus Faculdade de Ciências Médicas da Santa Casa de São Paulo Universidade Federal de São Paulo (UNIFESP) Universidade Estadual Paulista ‘Júlio de Mesquita Filho’ (UNESP) Departamento de Anestesiologia Associação de Medicina Intensiva Brasileira (AMIB) Hospital Geral de Fortaleza Centro Universitário Christus (UNICHRISTUS) Faculdade de Medicina Universidade Estadual Paulista ‘Júlio de Mesquita Filho’ (UNESP) Departamento de Anestesiologia

Purpose of review In this review, we aimed at providing the most recent and relevant clinical evidence regarding the use of nonventilatory strategies to prevent postoperative pulmonary complications (PPCs) after noncardiac surgery. Recent findings Although nonavoidable, most comorbidities can be modified in order to reduce the incidence of pulmonary events postoperatively. The physical status of patients suffering from chronic obstructive pulmonary disease, asthma, obstructive sleep apnea, and congestive heart failure can be improved preoperatively, and a number of measures can be undertaken to prevent PPCs, including physiotherapy for pulmonary rehabilitation and drug therapies. Also, smokers may benefit from both short and long-term smoke cessation. Furthermore, the risk of PPCs may be reduced upon: choice of an adequate anesthesia strategy (e.g. regional vs. general); appropriate neuromuscular blockade and reversal; use of volatile instead of intravenous anesthetics in lung surgery; judicious intravascular volume expansion (restrictive vs. liberal strategy); regional instead of systemic analgesia after major surgery in high-risk patients; more strict indication for nasogastric decompression in order to avoid silent aspiration; and laparoscopic instead of open bariatric surgery. Summary Nonventilatory strategies can play an important role in reducing PPCs and improving clinical outcome after noncardiac surgery, especially in high-risk patients.

Intravenous fluid administration is often required to counteract haemodynamic instability during emergency and elective surgeries, as well as in the intensive care unit. However, the best type and the amount of fluid required are controversial. A recent meta-analysis suggested that there is no difference among different types of colloids on outcome. Furthermore, colloids and crystalloids seem to be comparable in terms of efficiency in reverting haemodynamic instability, as well as morbidity and mortality. The interpretation of the results of different randomised controlled trials is somewhat difficult - the context must be always kept in mind. For example, results may differ in septic as compared to non-septic patient populations. Another important aspect concerns the effects on the macro- versus microcirculation. More recent studies emphasise that the microcirculation has to be taken into account when studying and interpreting the interaction between fluid therapy and the underlying disease. Nevertheless, the macrocirculation and clinical parameters have to be considered as well. Given that red blood cells remain the most important oxygen carriers, recent evidence regarding blood age may stimulate new studies according to the actual range for blood storage. Artificial oxygen carriers may play a role in specific situations, where the transfusion is indicated but the access to blood is problematic, but there is doubt that they may replace blood transfusion.

Objective:Volutrauma and atelectrauma promote ventilator-induced lung injury, but their relative contribution to inflammation in ventilator-induced lung injury is not well established. The aim of this study was to determine the impact of volutrauma and atelectrauma on the distribution of lung inflam

Parenchymal strain is a key determinant of lung injury produced by mechanical ventilation. However, imaging estimates of volumetric tidal strain (ε = regional tidal volume/reference volume) present substantial conceptual differences in reference volume computation and consideration of tidally recruited lung. We compared current and new methods to estimate tidal volumetric strains with computed tomography, and quantified the effect of tidal volume (VT) and positive end-expiratory pressure (PEEP) on strain estimates. Eight supine pigs were ventilated with VT= 6 and 12 ml/kg and PEEP = 0, 6, and 12 cmH2O. End-expiratory and end-inspiratory scans were analyzed in eight regions of interest along the ventral-dorsal axis. Regional reference volumes were computed at end-expiration (with/without correction of regional VTfor intratidal recruitment) and at resting lung volume (PEEP = 0) corrected for intratidal and PEEP-derived recruitment. All strain estimates demonstrated vertical heterogeneity with the largest tidal strains in middependent regions ( P < 0.01). Maximal strains for distinct estimates occurred at different lung regions and were differently affected by VT-PEEP conditions. Values consistent with lung injury and inflammation were reached regionally, even when global measurements were below critical levels. Strains increased with VTand were larger in middependent than in nondependent lung regions. PEEP reduced tidal-strain estimates referenced to end-expiratory lung volumes, although it did not affect strains referenced to resting lung volume. These estimates of tidal strains in normal lungs point to middependent lung regions as those at risk for ventilator-induced lung injury. The different conditions and topography at which maximal strain estimates occur allow for testing the importance of each estimate for lung injury.

Emphysema is characterized by loss of lung tissue elasticity and destruction of structures supporting alveoli and capillaries. The impact of mechanical ventilation strategies on ventilator-induced lung injury (VILI) in emphysema is poorly defined. New ventilator strategies should be developed to minimize VILI in emphysema. The present study was divided into two protocols: (1) characterization of an elastase-induced emphysema model in rats and identification of the time point of greatest cardiorespiratory impairment, defined as a high specific lung elastance associated with large right ventricular end-diastolic area; and (2) comparison between variable (VV) and conventional volume-controlled ventilation (VCV) on lung mechanics and morphometry, biological markers, and cardiac function at that time point. In the first protocol, Wistar rats (n = 62) received saline (SAL) or porcine pancreatic elastase (ELA) intratracheally once weekly for 4 weeks, respectively. Evaluations were performed 1, 3, 5, or 8 weeks after the last intratracheal instillation of saline or elastase. After identifying the time point of greatest cardiorespiratory impairment, an additional 32 Wistar rats were randomized into the SAL and ELA groups and then ventilated with VV or VCV (n = 8/group) [tidal volume (VT) = 6 mL/kg, positive end-expiratory pressure (PEEP) = 3 cmH2O, fraction of inspired oxygen (FiO2) = 0.4] for 2 h. VV was applied on a breath-to-breath basis as a sequence of randomly generated VT values (mean VT = 6 mL/kg), with a 30% coefficient of variation. Non-ventilated (NV) SAL and ELA animals were used for molecular biology analysis. The time point of greatest cardiorespiratory impairment, was observed 5 weeks after the last elastase instillation. At this time point, interleukin (IL)-6, cytokine-induced neutrophil chemoattractant (CINC)-1, amphiregulin, angiopoietin (Ang)-2, and vascular endothelial growth factor (VEGF) mRNA levels were higher in ELA compared to SAL. In ELA animals, VV reduced respiratory system elastance, alveolar collapse, and hyperinflation compared to VCV, without significant differences in gas exchange, but increased right ventricular diastolic area. Interleukin-6 mRNA expression was higher in VCV and VV than NV, while surfactant protein-D was increased in VV compared to NV. In conclusion, VV improved lung function and morphology and reduced VILI, but impaired right cardiac function in this model of elastase induced-emphysema.

This article is one of ten reviews selected from the Annual Update in Intensive Care and Emergency medicine 2016. Other selected articles can be found online at http://www.biomedcentral.com/collections/annualupdate2016. Further information about the Annual Update in Intensive Care and Emergency Medicine is available from http://www.springer.com/series/8901.

Background: Protective mechanical ventilation strategies using low tidal volume or high levels of positive end-expiratory pressure (PEEP) improve outcomes for patients who have had surgery. The role of the driving pressure, which is the difference between the plateau pressure and the level of positive end-expiratory pressure is not known. We investigated the association of tidal volume, the level of PEEP, and driving pressure during intraoperative ventilation with the development of postoperative pulmonary complications. Methods: We did a meta-analysis of individual patient data from randomised controlled trials of protective ventilation during general anesthaesia for surgery published up to July 30, 2015. The main outcome was development of postoperative pulmonary complications (postoperative lung injury, pulmonary infection, or barotrauma). Findings: We included data from 17 randomised controlled trials, including 2250 patients. Multivariate analysis suggested that driving pressure was associated with the development of postoperative pulmonary complications (odds ratio [OR] for one unit increase of driving pressure 1·16, 95% CI 1·13-1·19; p

Background Scant information exists about the epidemiological characteristics and outcome of patients in the intensive care unit (ICU) at risk of acute respiratory distress syndrome (ARDS) and how ventilation is managed in these individuals. We aimed to establish the epidemiological characteristics of patients at risk of ARDS, describe ventilation management in this population, and assess outcomes compared with people at no risk of ARDS. Methods PRoVENT (PRactice of VENTilation in critically ill patients without ARDS at onset of ventilation) is an international, multicentre, prospective study undertaken at 119 ICUs in 16 countries worldwide. All patients aged 18 years or older who were receiving mechanical ventilation in participating ICUs during a 1-week period between January, 2014, and January, 2015, were enrolled into the study. The Lung Injury Prediction Score (LIPS) was used to stratify risk of ARDS, with a score of 4 or higher defining those at risk of ARDS. The primary outcome was the proportion of patients at risk of ARDS. Secondary outcomes included ventilatory management (including tidal volume [VT] expressed as mL/kg predicted bodyweight [PBW], and positive end-expiratory pressure [PEEP] expressed as cm H2O), development of pulmonary complications, and clinical outcomes. The PRoVENT study is registered at ClinicalTrials.gov, NCT01868321. The study has been completed. Findings Of 3023 patients screened for the study, 935 individuals fulfilled the inclusion criteria. Of these critically ill patients, 282 were at risk of ARDS (30%, 95% CI 27–33), representing 0·14 cases per ICU bed over a 1-week period. VTwas similar for patients at risk and not at risk of ARDS (median 7·6 mL/kg PBW [IQR 6·7–9·1] vs 7·9 mL/kg PBW [6·8–9·1]; p=0·346). PEEP was higher in patients at risk of ARDS compared with those not at risk (median 6·0 cm H2O [IQR 5·0–8·0] vs 5·0 cm H2O [5·0–7·0]; p

Large tidal volume (VT) breaths or "recruitment maneuvers" (RMs) are used commonly to open collapsed lungs, but their effectiveness may depend on how the RM is delivered. We hypothesized that a stepped approach to RM delivery ("slow" RM) compared with a nonstepped ("fast" RM), when followed by decremental positive end-expiratory pressure (PEEP) titration to lowest dynamic elastance, would (1) yield a more homogeneous inflation of the lungs, thus reducing the PEEP obtained during post-RM titration; (2) produce less lung morphofunctional injury, regardless of the severity of sepsis-induced acute lung inflammation; and (3) result in less biological damage in severe, but not in moderate, acute lung inflammation.Sepsis was induced by cecal ligation and puncture surgery in 51 Wistar rats. After 48 hours, animals were anesthetized, mechanically ventilated (VT = 6 mL/kg), and stratified by PO2/fraction of inspired oxygen ratio into moderate (≥300) and severe (300) acute lung inflammation groups. Each group was then subdivided randomly into 3 subgroups: (1) nonrecruited; (2) RM with continuous positive airway pressure (30 cm H2O for 30 seconds; CPAPRM or fast RM); and (3) RM with stepwise airway pressure increase (5 cm H2O/step, 8.5 seconds/step, 6 steps, 51 seconds; STEPRM or slow RM), with a maximum pressure hold for 10 seconds. All animals underwent decremental PEEP titration to determine the level of PEEP required to optimize dynamic compliance after RM and were then ventilated for 60 minutes with VT = 6 mL/kg, respiratory rate = 80 bpm, fraction of inspired oxygen = 0.4, and the newly adjusted PEEP for each animal. Respiratory mechanics, hemodynamics, and arterial blood gases were measured before and at the end of 60-minute mechanical ventilation. Lung histology and biological markers of inflammation and damage inflicted to endothelial cells were evaluated at the end of the 60-minute mechanical ventilation.Respiratory system mean airway pressure was lower in STEPRM than that in CPAPRM. The total RM time was greater, and the RM rise angle was lower in STEPRM than that in CPAPRM. In both moderate and severe acute lung inflammation groups, STEPRM reduced total diffuse alveolar damage score compared with the score in nonrecruited rats. In moderate acute lung inflammation, STEPRM rats compared with CPAPRM rats had less endothelial cell damage and angiopoietin (Ang)-2 expression. In severe acute lung inflammation, STEPRM compared with CPAPRM reduced hyperinflation, endothelial cell damage, Ang-2, and intercellular adhesion molecule-1 expressions. RM rise angle correlated with Ang-2 expression.Compared with CPAPRM, STEPRM reduced biological markers associated with endothelial cell damage and ultrastructural endothelial cell injury in both moderate and severe sepsis-induced acute lung inflammation.

Several respiratory diseases feature increased inflammatory response and catabolic activity, which are associated with glutamine depletion; thus, the benefits of exogenous glutamine administration have been evaluated in clinical trials and models of different respiratory diseases. Recent reviews and meta-analyses have focused on the effects and mechanisms of action of glutamine in a general population of critical care patients or in different models of injury. However, little information is available about the role of glutamine in respiratory diseases. The aim of the present review is to discuss the evidence of glutamine depletion in cystic fibrosis (CF), asthma, chronic obstructive pulmonary disease (COPD), acute respiratory distress syndrome (ARDS), and lung cancer, as well as the results of exogenous glutamine administration in experimental and clinical studies. Exogenous glutamine administration might be beneficial in ARDS, asthma, and during lung cancer treatment, thus representing a potential therapeutic tool in these conditions. Further experimental and large randomized clinical trials focusing on the development and progression of respiratory diseases are necessary to elucidate the effects and possible therapeutic role of glutamine in this setting.

Purpose of review We discuss the possible role of computed tomography (CT) to guide protective mechanical ventilation in acute lung injury/acute respiratory distress syndrome (ALI/ARDS), especially tidal volume (VT) and positive-end expiratory pressure (PEEP) settings and recruitment manoeuvres. Recent findings CT should be used as early as possible after the onset of ALI/ARDS and then repeated after 1 week in the absence of clinical improvement. Advantages of CT include: the regional response to recruitment can be determined; it is objective; the morphofunctional correlations obtained are useful for a comprehensive patient evaluation. CT should be performed at different pressure levels to identify potential for recruitment. Initially, one single whole-lung CT scan is performed at end-expiration at PEEP 5-10 cmH2O to evaluate aeration and compute lung weight. Afterwards, two lung CT slices are performed to assess lung recruitability (at PEEP = 5-10 cmH2O; inspiratory plateau pressure of the respiratory system = 45 cmH2O). Summary In ALI/ARDS patients, CT reveals discrepancies between bedside chest radiograph and various clinical and physiological parameters, and it is essential to assess lung morphology and recruitability. Specific algorithms, including or not CT, should be used to better identify ALI/ARDS with potential of recruitment and setting of VT and PEEP.

To investigate the effects of the rate of airway pressure increase and duration of recruitment maneuvers on lung function and activation of inflammation, fibrogenesis, and apoptosis in experimental acute lung injury.Prospective, randomized, controlled experimental study.University research laboratory.Thirty-five Wistar rats submitted to acute lung injury induced by cecal ligation and puncture.After 48 hrs, animals were randomly distributed into five groups (seven animals each): 1) nonrecruited (NR); 2) recruitment maneuvers (RMs) with continuous positive airway pressure (CPAP) for 15 secs (CPAP15); 3) RMs with CPAP for 30 secs (CPAP30); 4) RMs with stepwise increase in airway pressure (STEP) to targeted maximum within 15 secs (STEP15); and 5) RMs with STEP within 30 secs (STEP30). To perform STEP RMs, the ventilator was switched to a CPAP mode and positive end-expiratory pressure level was increased stepwise. At each step, airway pressure was held constant. RMs were targeted to 30 cm H2O. Animals were then ventilated for 1 hr with tidal volume of 6 mL/kg and positive end-expiratory pressure of 5 cm H2O.Blood gases, lung mechanics, histology (light and electronic microscopy), interleukin-6, caspase 3, and type 3 procollagen mRNA expressions in lung tissue. All RMs improved oxygenation and lung static elastance and reduced alveolar collapse compared to NR. STEP30 resulted in optimal performance, with: 1) improved lung static elastance vs. NR, CPAP15, and STEP15; 2) reduced alveolar-capillary membrane detachment and type 2 epithelial and endothelial cell injury scores vs. CPAP15 (p.05); and 3) reduced gene expression of interleukin-6, type 3 procollagen, and caspase 3 in lung tissue vs. other RMs.Longer-duration RMs with slower airway pressure increase efficiently improved lung function, while minimizing the biological impact on lungs.

In acute lung injury (ALI), pressure support ventilation (PSV) may improve oxygenation compared with pressure-controlled ventilation (PCV), and benefit from random variation of pressure support (noisy PSV). We investigated the effects of PCV, PSV, and noisy PSV on gas exchange as well as the distribution of lung aeration and perfusion in 12 pigs with ALI induced by saline lung lavage in supine position. After injury, animals were mechanically ventilated with PCV, PSV, and noisy PSV for 1 h/mode in random sequence. The driving pressure was set to a mean tidal volume of 6 ml/kg and positive end-expiratory pressure to 8 cmH2O in all modes. Functional variables were measured, and the distribution of lung aeration was determined by static and dynamic computed tomography (CT), whereas the distribution of pulmonary blood flow (PBF) was determined by intravenously administered fluorescent microspheres. PSV and noisy PSV improved oxygenation and reduced venous admixture compared with PCV. Mechanical ventilation with PSV and noisy PSV did not decrease nonaerated areas but led to a redistribution of PBF from dorsal to ventral lung regions and reduced tidal reaeration and hyperinflation compared with PCV. Noisy PSV further improved oxygenation and redistributed PBF from caudal to cranial lung regions compared with conventional PSV. We conclude that assisted ventilation with PSV and noisy PSV improves oxygenation compared with PCV through redistribution of PBF from dependent to nondependent zones without lung recruitment. Random variation of pressure support further redistributes PBF and improves oxygenation compared with conventional PSV.

In the last 20 years, the use of computed tomography (CT) to evaluate thoracic diseases has rapidly gained popularity and CT has become firmly established as an important research and diagnostic modality. In particular, CT has played an important role in improving our knowledge about the pathophysiology of the adult respiratory distress syndrome (ARDS) and in determining the morphological and functional relationships of different therapeutic options commonly used in the clinical management of this syndrome. CT scan may provide: 1) accurate measurement of the impact of mechanical ventilation on hyperaeration and reaeration/recruitment, being the most objective technique currently available to set mechanical ventilation and identifying patients for extracorporeal lung support; 2) the amount of lung edema, associated with the severity of the alveolar capillary barrier lesion and the risk of mortality; 3) clinical information in patients with a sudden and unexplained deterioration of the clinical status or the lack of expected improvement as well as to follow the evolution with time. We recommend to perform: 1) one single whole lung CT scan at end-expiration at PEEP 5 cmH2O, to evaluate the distribution of aeration and to compute the amount of lung weight; 2) only three lung CT slices, taken at the lung apex, hilum, and basis, at PEEP = 5 cmH2O and at Pplat = 45 cmH2O, to assess of lung recruitability; 3) a CT scan as early as possible after onset of ARDS (if clinical characteristics persist for more than 24 hours) and repeat it after 1 week if no clinical improvement is observed; 4) a CT scan in presence of any clinical deterioration not explained by conventional diagnostic tools. We suggest considering the measurement of extravascular lung water and end-expiratory lung volume by non radiological techniques and lung ultrasound if CT scan cannot be done.

The pressure across the lung, so-called transpulmonary pressure (P L ), represents the main force acting toward to provide lung movement. During mechanical ventilation, P L is provided by respiratory system pressurization, using specific ventilator setting settled by the operator, such as: tidal volume (V T ), positive end-expiratory pressure (PEEP), respiratory rate (RR), and inspiratory airway flow. Once P L is developed throughout the lungs, its distribution is heterogeneous, being explained by the elastic properties of the lungs and pleural pressure gradient. There are different methods of P L calculation, each one with importance and some limitations. Among the most known, it can be quoted: (I) direct measurement of P L ; (II) elastance derived method at end-inspiration of P L ; (III) transpulmonary driving pressure. Recent studies using pleural sensors in large animal models as also in human cadaver have added new and important information about P L heterogeneous distribution across the lungs. Due to this heterogeneous distribution, lung damage could happen in specific areas of the lung. In addition, it is widely accepted that high P L can cause lung damage, however the way it is delivered, whether it’s compressible or tensile, may also further damage despite the values of P L achieved. According to heterogeneous distribution of P L across the lungs, the interstitium and lymphatic vessels may also interplay to disseminate lung inflammation toward peripheral organs through thoracic lymph tracts. Thus, it is conceivable that juxta-diaphragmatic area associated strong efforts leading to high values of P L may be a source of dissemination of inflammatory cells, large molecules, and plasma contents able to perpetuate inflammation in distal organs.

Inhalation of perfluorohexane vapor (PFH) and high-frequency oscillatory ventilation (HFOV) both have been shown to improve lung function in acute lung injury (ALI). Their combination implies synergistic action. The authors investigated technical aspects of PFH vaporization during HFOV and effects on gas exchange in a pilot study of experimental ALI. Eighteen anesthetized sheep were randomly assigned to HFOV or HFOV with PFH inhalation after oleic acid-induced ALI. HFOV was set to a continuous distending pressure of 25 cm H₂O, and an oscillation of 80 to 100 cm H₂O at a frequency of 5 Hz. PFH vapor was delivered by means of bypassed high-flow oxygen through a thin endotracheal tube. PFH concentration was measured by infrared absorption. Blood gases and hemodynamic data were taken. PaO₂ significantly increased from 9.1 ± 0.9 to 32.7 ± 9.5 kPa (mean ± SEM) in the HFOV group and from 12.5 ± 1.1 to 27.0 ± 6.8 kPa in the HFOV PFH group. PaCO₂ significantly decreased from 6.3 ± 0.3 to 5.5 ± 0.5 kPa in the HFOV group and from 5.7 ± 0.4 to 4.9 ± 0.5 kPa in the HFOV PFH group. Changes in gas exchange were not different between groups. These results show that the inhalation of PFH during HFOV is technically feasible, but did not enhance gas exchange in a 210-minute observation period of experimental ALI.

In patients with acute lung injury and acute respiratory distress syndrome, a protective mechanical ventilation strategy characterized by low tidal volumes has been associated with reduced mortality. However, such a strategy may result in alveolar collapse, leading to cyclic opening and closing of atelectatic alveoli and distal airways. Thus, recruitment maneuvers (RMs) have been used to open up collapsed lungs, while adequate positive end-expiratory pressure (PEEP) levels may counteract alveolar derecruitment during low tidal volume ventilation, improving respiratory function and minimizing ventilator-associated lung injury. Nevertheless, considerable uncertainty remains regarding the appropriateness of RMs. The most commonly used RM is conventional sustained inflation, associated with respiratory and cardiovascular side effects, which may be minimized by newly proposed strategies: prolonged or incremental PEEP elevation; pressure-controlled ventilation with fixed PEEP and increased driving pressure; pressure-controlled ventilation applied with escalating PEEP and constant driving pressure; and long and slow increase in pressure. The efficiency of RMs may be affected by different factors, including the nature and extent of lung injury, capability of increasing inspiratory transpulmonary pressures, patient positioning and cardiac preload. Current evidence suggests that RMs can be used before setting PEEP, after ventilator circuit disconnection or as a rescue maneuver to overcome severe hypoxemia; however, their routine use does not seem to be justified at present. The development of new lung recruitment strategies that have fewer hemodynamic and biological effects on the lungs, as well as randomized clinical trials analyzing the impact of RMs on morbidity and mortality of acute lung injury/acute respiratory distress syndrome patients, are warranted.

There is growing interest in the use of both variable and pressure-controlled ventilation (PCV). The combination of these approaches as “noisy PCV” requires adaptation of the mechanical ventilator to the respiratory system mechanics. Thus, we developed and evaluated a new control system based on the least-mean-squares adaptive approach, which automatically and continuously adjusts the driving pressure during PCV to achieve the desired variability pattern of tidal volume (V T). The controller was tested during numerical simulations and with a physical model reproducing the mechanical properties of the respiratory system. We applied step changes in respiratory system mechanics and mechanical ventilation settings. The time needed to converge to the desired V T variability pattern after each change (t c) and the difference in minute ventilation between the measured and target pattern of V T (ΔMV) were determined. During numerical simulations, the control system for noisy PCV achieved the desired variable V T pattern in less than 30 respiratory cycles, with limited influence of the dynamic elastance (E*) on t c, except when E* was underestimated by >25%. We also found that, during tests in the physical model, the control system converged in

Spontaneous breathing (SB) activity may improve gas exchange during mechanical ventilation mainly by the recruitment of previously collapsed regions. Pressure support ventilation (PSV) and biphasic positive airway pressure (BIPAP) are frequently used modes of SB, but little is known about the mechanisms of improvement of lung function during these modes of assisted mechanical ventilation. We evaluated the mechanisms behind the improvement of gas exchange with PSV and BIPAP.Five pigs (25-29.3 kg) were mechanically ventilated in supine position, and acute lung injury (ALI) was induced by surfactant depletion. After stabilization, BIPAP was initiated with lower continuous positive airway pressure equal to 5 cm H2O and the higher continuous positive airway pressure titrated to achieve a tidal volume between 6 and 8 mL/kg. The depth of anesthesia was reduced, and when SB representedor = 20% of total minute ventilation, PSV and BIPAP + SB were each performed for 1 h (random sequence). Whole chest helical computed tomography was performed during end-expiratory pauses and functional variables were obtained. Pulmonary blood flow (PBF) was marked with IV administered fluorescent microspheres, and spatial cluster analysis was used to determine the effects of each ventilatory mode on the distribution of PBF.ALI led to impairment of lung function and increase of poorly and nonaerated areas in dependent lung regions (P0.05). PSV and BIPAP + SB similarly improved oxygenation and reduced venous admixture compared with controlled mechanical ventilation (P0.05). Despite that, a significant increase of nonaerated areas in dependent regions with a concomitant decrease of normally aerated areas was observed during SB. In five of six lung clusters, redistribution of PBF from dependent to nondependent, better aerated lung regions were observed during PSV and BIPAP + SB.In this model of ALI, the improvements of oxygenation and venous admixture obtained during assisted mechanical ventilation with PSV and BIPAP + SB were explained by the redistribution of PBF toward nondependent lung regions rather than recruitment of dependent zones.

Background Noisy pressure support ventilation has been reported to improve respiratory function compared to conventional assisted mechanical ventilation. We aimed at determining the optimal level of pressure support variability during noisy pressure support ventilation. Methods Twelve pigs were anesthetized and mechanically ventilated. Acute lung injury was induced by surfactant depletion. At four levels of pressure support variability (coefficients of variation of pressure support equal to 7.5, 15, 30, and 45%, 30 min each, crossover design, special Latin squares sequence), we measured respiratory variables, gas exchange, hemodynamics, inspiratory effort, and comfort of breathing. The mean level of tidal volume was constant among variability levels. Results Compared to conventional pressure support ventilation, different levels of variability in pressure support improved the elastance of the respiratory system, peak airway pressure, oxygenation, and intrapulmonary shunt. Oxygenation and venous admixture benefited more from intermediate (30%) levels of variability, whereas elastance and peak airway pressure improved linearly with increasing variability. Heart rate as well as mean arterial and pulmonary arterial pressures decreased slightly at intermediate to high (30-45%) levels of variability in pressure support. Inspiratory effort and comfort of breathing were not importantly influenced by increased variability in pressure support. Conclusion In a surfactant depletion model of acute lung injury, variability of pressure support improves lung function. The variability level of 30% seems to represent a reasonable compromise to improve lung functional variables during noisy pressure support ventilation.

Summary Background & aims Omega-3 fatty acids (FA) have been shown to reduce morbidity and mortality. Aim of this study was to evaluate acute effects in a multicenter database with regard to outcome arising from varying ratios of omega-3 vs. omega-6 FA independent from the underlying dose of eicosapentaenoic acid or docosahexaenoic acid. Methods Six hundred and sixty-one patients from 82 German hospitals receiving total parenteral nutrition including fish oil for at least 3 consecutive days participated in this study. The sample included 255 patients after major abdominal surgery and 276 with peritonitis and abdominal sepsis. Length of stay and use of antibiotics were analyzed with respect to their diagnosis. Results A mean dose of eicosapentaenoic and docosahexaenoic acid of 56±16 mg/kg/d was infused. Most favorable effects on length of ICU stay were observed when the omega-3/omega-6 ratio was Conclusion Despite the present post-hoc evaluation merely allows hypotheses generating conclusions, the omega-3/omega-6 ratio diagnosis dependently affected clinical outcome in a large number of patients independent from the fish oil dosage. At a given dosage an omega-3/omega-6 FA ratio of