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Ultrasound-guided intermediate cervical plexus blockade with perivascular infiltration of the carotid artery bifurcation perivacular block (PVB) is a reliable technique for regional anesthesia in carotid endarterectomy (CEA). We investigated the effect of the carotid bifurcation level (CBL) on PVB efficacy and safety in patients undergoing CEA. This prospective observational cohort study included 447 consecutive CEA patients who received PVB over a 6-y period. Vascular and neurologic puncture-related complications were recorded. The CBL was localized at the low level (C4 and C5 vertebra, low-level [LL] group) in 381 (85.2%) patients and at the high level (C2 and C3 vertebra, high-level [HL] group) in 66 (14.8%) patients. Local anesthetic supplementation by surgeons was necessary in 64 (14.3%) patients in the LL group and 38 (59.4%) patients in the HL group (p < 0.001) and was associated with a higher rate of central neurologic complications in the HL group (p = 0.031). Therefore, the efficacy of the PVB may be influenced by the CBL.

Background: In reconstructive surgery, loss of a microvascular free flap due to perfusion disorders, especially thrombosis, is a serious complication. In recent years, viscoelastic testing (VET) has become increasingly important in point-of-care (POC) anticoagulation monitoring. This paper describes a protocol for enhanced anticoagulation monitoring during maxillofacial flap surgery. Objective: The aim of the study will be to evaluate, in a controlled setting, the predictive value of POC devices for the type of flap perfusion disorders due to thrombosis or bleeding. VET, Platelet monitoring (PM) and standard laboratory tests (SLT) are comparatively examined. Methods/Design: This study is an investigator-initiated prospective trial in 100 patients undergoing maxillofacial surgery. Patients who undergo reconstructive surgery using microvascular-free flaps will be consecutively enrolled in the study. All patients provide blood samples for VET, PM and SLT at defined time points. The primary outcome is defined as free flap loss during the hospital stay. Statistical analyses will be performed using t-tests, including the Bonferroni adjustment for multiple comparisons. Discussion: This study will help clarify whether VET can improve individualized patient care in reconstruction surgery. A better understanding of coagulation in relation to flap perfusion disorders may allow real-time adaption of antithrombotic strategies and potentially prevent flap complications.

Point of care (POC) devices are increasingly used in the ICU and in anesthesia. Besides POC-devices for blood gas analysis, several devices are available for coagulation measurements. Although basic principles for thromboelastographic measurements are not novel, some promising developments were made during the last decade improving both user-friendliness and measurement reliability. For instance, POC measurements of activated clotting time (ACT) for heparin monitoring is still regarded as standard-of-care in cardiac interventions and surgery. In the field of anesthesia and intensive care medicine, POC-devices for thromboelastographic and platelet aggregation measurements are widely used. Their impact in case of bleeding and patient blood management for cardiothoracic and trauma surgery is well known. Moreover, there are promising concepts for anticoagulation monitoring including new oral anticoagulant drugs. Coagulation POC-devices may also identify patients at specific risk for thromboembolic events quickly. On the other hand, benefits of POC-devices need to be balanced against limitations, which include technical restrictions and operator related errors, mainly affecting reproducibility and interpretation of results. Therefore, it is recommendable to consider results of POC-coagulation testing in comparison to standard laboratory tests (SLT). Nevertheless, in urgent or emergency situations POC results enable fast decision making to optimize patient care.

BACKGROUND: COVID-19 convalescent plasma (CCP) has been considered a treatment option for COVID-19. This trial assessed the efficacy of a neutralizing antibody containing high-dose CCP in hospitalized adults with COVID-19 requiring respiratory support or intensive care treatment. METHODS: Patients (n = 105) were randomized 1:1 to either receive standard treatment and 3 units of CCP or standard treatment alone. Control group patients with progress on day 14 could cross over to the CCP group. The primary outcome was a dichotomous composite outcome of survival and no longer fulfilling criteria for severe COVID-19 on day 21. RESULTS: The primary outcome occurred in 43.4% of patients in the CCP group and 32.7% in the control group (P = 0.32). The median time to clinical improvement was 26 days in the CCP group and 66 days in the control group (P = 0.27). The median time to discharge from the hospital was 31 days in the CCP group and 51 days in the control group (P = 0.24). In the subgroup that received a higher cumulative amount of neutralizing antibodies, the primary outcome occurred in 56.0% of the patients (vs. 32.1%), with significantly shorter intervals to clinical improvement (20 vs. 66 days, P < 0.05) and to hospital discharge (21 vs. 51 days, P = 0.03) and better survival (day-60 probability of survival 91.6% vs. 68.1%, P = 0.02) in comparison with the control group. CONCLUSION: CCP added to standard treatment was not associated with a significant improvement in the primary and secondary outcomes. A predefined subgroup analysis showed a significant benefit of CCP among patients who received a larger amount of neutralizing antibodies. TRIAL REGISTRATION: ClinicalTrials.gov NCT04433910. FUNDING: Bundesministerium für Gesundheit (German Federal Ministry of Health): ZMVI1-2520COR802.

Summary Background & aims Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection can rapidly progress into acute respiratory distress syndrome accompanied by multi-organ failure requiring invasive mechanical ventilation and critical care treatment. Nutritional therapy is a fundamental pillar in the management of hospitalized patients. It is broadly acknowledged that overfeeding and underfeeding of intensive care unit (ICU) patients are associated with increased morbidity and mortality. This study aimed to assess the energy demands of long-term ventilated COVID-19 patients using indirect calorimetry and to evaluate the applicability of established predictive equations to estimate their energy expenditure. Methods We performed a retrospective, single-center study in 26 mechanically ventilated COVID-19 patients with resolved SARS-CoV-2 infection in three independent intensive care units. Resting energy expenditure (REE) was evaluated by repetitive indirect calorimetry (IC) measurements. Simultaneously the performance of 12 predictive equations was examined. Patient's clinical data were retrieved from electronic medical charts. Bland-Altman plots were used to assess agreement between measured and calculated REE. Results Mean mREE was 1687 kcal/day and 20.0 kcal relative to actual body weight (ABW) per day (kcal/kg/day). Longitudinal mean mREE did not change significantly over time, although mREE values had a high dispersion (SD of mREE ±487). Obese individuals were found to have significantly increased mREE, but lower energy expenditure relative to their body mass. Calculated REE showed poor agreement with mREE ranging from 33 to 54%. Conclusion Resolution of SARS-CoV-2 infection confirmed by negative PCR leads to stabilization of energy demands at an average 20 kcal/kg in ventilated critically ill patients. Due to high variations in mREE and low agreement with calculated energy expenditure IC remains the gold standard for the guidance of nutritional therapy.

Rationale: COVID-19 convalescent plasma (CCP) has been considered a treatment option in COVID-19. Objectives:: To assess the efficacy of neutralizing antibody containing high-dose CCP in hospitalized adults with COVID-19 requiring respiratory support or intensive care treatment. Methods: Patients (n=105) were randomized 1:1 to either receive standard treatment and 3 units of CCP or standard treatment alone. Control group patients with progress on day 14 could cross over to the CCP group. Primary outcome was a dichotomous composite outcome of survival and no longer fulfilling criteria for severe COVID-19 on day 21. The trial is registered: clinicaltrials.gov #NCT04433910. Measurements and main results: The primary outcome occurred in 43.4% of patients in the CCP and 32.7% in the control group (p=0.32). The median time to clinical improvement was 26 days (IQR 15-not reached (n.r.)) in the CCP group and 66 days (IQR 13-n.r.) in the control group (p=0.27). Median time to discharge from hospital was 31 days (IQR 16-n.r.) in the CCP and 51 days (IQR 20-n.r.) in the control group (p=0.24). In the subgroup that received a higher cumulative amount of neutralizing antibodies the primary outcome occurred in 56.0% (versus 32.1%), with a shorter interval to clinical improvement, shorter time to hospital discharge and better survival compared to the control group. Conclusion: CCP added to standard treatment did not result in a significant difference in the primary and secondary outcomes. A pre-defined subgroup analysis showed a significant benefit for CCP among those who received a larger amount of neutralizing antibodies. Primary Funding Source: Bundesministerium fuer Gesundheit

Neurological outcome and quality of live are of uttermost interest in survivors of cardiac arrest. Assuming acceptable rates of return of spontaneous circulation, the long-term effects on neurological function and quality of live after cardiopulmonary resuscitation remain unsatisfactory. Extracorporeal cardiopulmonary resuscitation (eCPR) can reduce low-flow times and therefore provide adequate cerebral tissue perfusion and oxygenation. This may improve favorable outcomes after cardiac arrest. Due to the risk of procedure related complications and ethical issues, this technique should be only performed in selected patients by specially trained and experienced teams. In this review we aimed at providing an insight into the sparse evidence in this field and discussing ethical issues associated with the use of eCPR.

Radiation-induced pulmonary fibrosis is a common severe long-time complication of radiation therapy for tumors of the thorax. Current therapeutic options used in the clinic include only supportive managements strategies, such as anti-inflammatory treatment using steroids, their efficacy, however, is far from being satisfactory. Recent studies have demonstrated that the development of lung fibrosis is a dynamic and complex process, involving the release of reactive oxygen species, activation of Toll-like receptors, recruitment of inflammatory cells, excessive production of nitric oxide and production of collagen by activated myofibroblasts. In this review we summarized the current state of knowledge on the pathophysiological processes leading to the development of lung fibrosis and we also discussed the possible treatment options.

PubMed: 32118384 [No abstract available]

The therapy of patients suffering from sepsis and septic shock is one of the greatest challenges in critical care medicine. In the initial phase of septic shock patients often present with hyperdynamic circulatory conditions with elevated cardiac index, tachycardia and progressive hemodynamic instability. The type of tachycardia differs from atrial fibrillation or flatter to sinus tachycardia. The latter might be persistent even in case of adequate volume therapy according to the surviving sepsis campaign recommendations and may represent an independent pathology due to adrenergic overstimulation. Despite predominantly β2-mediated immunomodulatory effects the administration of a selective β1-adrenergic blocker may be beneficial in some cases. On the other hand, incautious administration of beta-blockers especially in case of insufficient volume replacement may result in direct negative inotropic effects rapidly aggravating hypotension and shock. This review focused on pharmacology of the β-adrenergic system, the pathophysiological rationale and current literature on clinical practice of the use of beta-blockers in sepsis and septic shock.

Chest imaging in patients with acute respiratory failure plays an important role in diagnosing, monitoring and assessing the underlying disease. The available modalities range from plain chest X-ray to computed tomography, lung ultrasound, electrical impedance tomography and positron emission tomography. Surprisingly, there are presently no clear-cut recommendations for critical care physicians regarding indications for and limitations of these different techniques.The purpose of the present European Respiratory Society (ERS) statement is to provide physicians with a comprehensive clinical review of chest imaging techniques for the assessment of patients with acute respiratory failure, based on the scientific evidence as identified by systematic searches. For each of these imaging techniques, the panel evaluated the following items: possible indications, technical aspects, qualitative and quantitative analysis of lung morphology and the potential interplay with mechanical ventilation. A systematic search of the literature was performed from inception to September 2018. A first search provided 1833 references. After evaluating the full text and discussion among the committee, 135 references were used to prepare the current statement.These chest imaging techniques allow a better assessment and understanding of the pathogenesis and pathophysiology of patients with acute respiratory failure, but have different indications and can provide additional information to each other.

Acute respiratory distress syndrome (ARDS) is a common disease entity in critical care medicine and is still associated with a high mortality. Because of the heterogeneous character of ARDS, animal models are an insturment to study pathology in relatively standardized conditions. Rodent models can bridge the gap from in vitro investigations to large animal and clinical trials by facilitating large sample sizes under physiological conditions at comparatively low costs. One of the most commonly used rodent models of acute lung inflammation and ARDS is administration of lipopolysaccharide (LPS), either into the airways (direct, pulmonary insult) or systemically (indirect, extra-pulmonary insult). This narrative review discusses the dynamics of important pathophysiological pathways contributing to the physiological response to LPS-induced injury. Pathophysiological pathways of LPS-induced lung injury are not only influenced by the type of the primary insult (e.g., pulmonary or extra-pulmonary) and presence of additional stimuli (e.g., mechanical ventilation), but also by time. As such, findings in animal models of LPS-induced lung injury may depend on the time point at which samples are obtained and physiological data are captured. This review summarizes the current evidence and highlights uncertainties on the molecular dynamics of LPS-induced lung injury in rodent models, encouraging researchers to take accurate timing of LPS-induced injury into account when designing experimental trials.

Reducing ventilator-associated lung injury by individualized mechanical ventilation (MV) in patients with Acute Respiratory Distress Syndrome (ARDS) remains a matter of research. We randomly assigned 27 pigs with acid aspiration-induced ARDS to three different MV protocols for 24 h, targeting different magnitudes of collapse and tidal recruitment (collapse&amp, TR): the ARDS-network (ARDSnet) group with low positive end-expiratory pressure (PEEP) protocol (permissive collapse&amp, TR), the Open Lung Concept (OLC) group, PaO2/FiO2 &gt, 400 mmHg, indicating collapse&amp, TR &lt, 10%, and the minimized collapse&amp, TR monitored by Electrical Impedance Tomography (EIT) group, standard deviation of regional ventilation delay, SDRVD. We analyzed cardiorespiratory parameters, computed tomography (CT), EIT, and post-mortem histology. Mean PEEP over post-randomization measurements was significantly lower in the ARDSnet group at 6.8 &plusmn, 1.0 cmH2O compared to the EIT (21.1 &plusmn, 2.6 cmH2O) and OLC (18.7 &plusmn, 3.2 cmH2O) groups (general linear model (GLM) p &lt, 0.001). Collapse&amp, TR and SDRVD, averaged over all post-randomization measurements, were significantly lower in the EIT and OLC groups than in the ARDSnet group (collapse p &lt, 0.001, TR p = 0.006, SDRVD p &lt, 0.004). Global histological diffuse alveolar damage (DAD) scores in the ARDSnet group (10.1 &plusmn, 4.3) exceeded those in the EIT (8.4 &plusmn, 3.7) and OLC groups (6.3 &plusmn, 3.3) (p = 0.16). Sub-scores for edema and inflammation differed significantly (ANOVA p &lt, 0.05). In a clinically realistic model of early ARDS with recruitable and nonrecruitable collapse, mechanical ventilation involving recruitment and high-PEEP reduced collapse&amp, TR and resulted in improved hemodynamic and physiological conditions with a tendency to reduced histologic lung damage.

Objectives There has been multiple advances in the management of acute respiratory distress syndrome, but the temporal trends in acute respiratory distress syndrome-related mortality are not well known. This study aimed to investigate the trends in mortality in acute respiratory distress syndrome patients over time and to explore the roles of daily fluid balance and ventilation variables in those patients. Design Secondary analysis of randomized controlled trials conducted by the Acute Respiratory Distress Syndrome Network from 1996 to 2013. Setting Multicenter study involving Acute Respiratory Distress Syndrome Network trials. Patients Patients with acute respiratory distress syndrome. Interventions None. Measures and main results Individual patient data from 5,159 acute respiratory distress syndrome patients (excluding the Late Steroid Rescue Study trial) were enrolled in this study. The crude mortality rate decreased from 35.4% (95% CI, 29.9-40.8%) in 1996 to 28.3% (95% CI, 22.0-34.7%) in 2013. By adjusting for the baseline Acute Physiology and Chronic Health Evaluation III, age, ICU type, and admission resource, patients enrolled from 2005 to 2010 (odds ratio, 0.61; 95% CI, 0.50-0.74) and those enrolled after 2010 (odds ratio, 0.73; 95% CI, 0.58-0.92) were associated with lower risk of death as compared to those enrolled before 2000. The effect of year on mortality decline disappeared after adjustment for daily fluid balance, positive end-expiratory pressure, tidal volume, and plateau pressure. There were significant trends of declines in daily fluid balance, tidal volume, and plateau pressure and an increase in positive end-expiratory pressure over the 17 years. Conclusions Our study shows an improvement in the acute respiratory distress syndrome-related mortality rate in the critically ill patients enrolled in the Acute Respiratory Distress Syndrome Network trials. The effect was probably mediated via decreased tidal volume, plateau pressure, and daily fluid balance and increased positive end-expiratory pressure.

Rationale We investigated the effects of vaporized perfluorohexane (PFH) on pulmonary vascular tone, pulmonary vascular resistance and peak inspiratory pressure as well as lipid mediator formation in the treatment of calcium ionophore induced lung injury in a model of the isolated perfused and ventilated rabbit lungs. Methods Lung injury was induced in isolated perfused and ventilated rabbit lungs by calcium ionophore A23187. Lungs were treated with either 4.5 vol.% (4.5 vol.% PFH; n = 6) or 18 vol.% (18 vol.% PFH; n = 6) PFH. Six lungs remained untreated (Control). In addition 5 lungs (PFH-sham) remained uninjured receiving 18 vol.% PFH only. Mean pulmonary artery pressure (mPAP), peak inspiratory pressure ( P max ), and lung weight (weight) were monitored for 120 min. Experiments were terminated before when the increase in lung weight exceeded 40 g. Perfusate samples were taken at regular intervals for analysis of TXB 2 , 6-keto-PGF 1 and LTB 4 . Results Controls reached the study end point significantly earlier than both PFH groups. Significant differences were found for a weight gain of 10 g and 20 g between the control and the 4.5 vol.% PFH and the 18 vol.% PFH. Differences in mPAP were more pronounced in the 4.5 vol.% PFH. However increases in P max were more marked in 4.5 vol.% PFH. TXA 2 -, PGI 2 -, and LTB 4 -levels were significantly lower in PFH groups. Uninjured lungs remained unaffected by the presence of 18 vol.% PFH. Conclusion Inflammatory lung injury was attenuated by the treatment with 4.5 vol.% PFH and 18 vol.% PFH vapor in the isolated perfused rabbit lung. Therapeutic effects were more pronounced with a concentration of 4.5 vol.% PFH.

„Dreckserkrankung!“ Herr May wollte eigentlich laut fluchen, aber dafur war die Luft zu knapp. Er stand mit aufgestutzten Armen am Kuchentisch und keuchte. Sein Asthmaspray hatte er leergepumpt und sich dann eine Mentholzigarette angesteckt. „Damit werde ich so alt wie Helmut Schmidt!“ kommentierte er stets die Vorwurfe von Freunden. In der Tat hatte ihm der Mentholdampf schon manchmal Erleichterung verschafft – aber nicht heute. In diesem Kapitel geht es um Asthma, Zeitkonstante, ECMO, Medikamentenuberhang, Neuromonitoring, Ketamin sowie Safety-I versus Safety-II.

The aim of the present review was to concisely summarize recent studies and current knowledge about effects of red blood cell storage injury in trauma patients.Despite a pathophysiological rationale for older packed red blood cells (PRBCs) being associated with adverse events in the host organism, recent large clinical trials failed to show negative effects of transfusion with older PRBCs on clinically relevant outcomes in mixed patient population. However, there is a lack of well-designed randomized controlled trials focusing on the effects of storage lesion of PRBCs in trauma patients.In the absence of specific evidence for trauma patients, we recommend to continue with a conservative transfusion regime and standard of care blood banking practice of using older PRBCs first.

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.

Transportation of a patient between medical facilities without interruption of the medical treatment can be a challenging task. This review aims to define the term "interhospital transport" and give a general overview of the steps for organizing a transfer. Furthermore we discuss the team qualification, equipment standards and how to manage adverse events before and during transport by means of patient triage. The advanced interhospital transport of the critically ill patient can be defined as follows: "transportation of a patient between medical facilities without interruption of the medical treatment and monitoring due to the underlying disease by means of specific medical, technical equipment and knowledge with the objective of improved patient care." Several organizational steps come along with patients transfer: the hospital of origin has to identify transfer-eligible patients and be willing to release the patient. It has to identify a destination hospital and negotiate the transfer; the patient has to be transportable, the patient/relatives must agree; the transporting unit has to have the infrastructure and acknowledge to transport the patient; the insurance company or the family has to guarantee for the additional costs. Relocation team members need a specific training that focus on typical critical events that happen during transport. Technical equipment (ventilator, stretcher, monitor, defibrillator, external pacemaker, blood-gas analyzer) facilitates smooth patient transition from one facility to a distant one. The use of checklists is associated with a reduction of incidents during the transport.

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.

One of the most challenging problems in critical care medicine is the management of patients with the acute respiratory distress syndrome. Increasing evidence from experimental and clinical studies suggests that mechanical ventilation, which is necessary for life support in patients with acute respiratory distress syndrome, can cause lung fibrosis, which may significantly contribute to morbidity and mortality. The role of mechanical stress as an inciting factor for lung fibrosis versus its role in lung homeostasis and the restoration of normal pulmonary parenchymal architecture is poorly understood. In this review, the authors explore recent advances in the field of pulmonary fibrosis in the context of acute respiratory distress syndrome, concentrating on its relevance to the practice of mechanical ventilation, as commonly applied by anesthetists and intensivists. The authors focus the discussion on the thesis that mechanical ventilation—or more specifically, that ventilator-induced lung injury—may be a major contributor to lung fibrosis. The authors critically appraise possible mechanisms underlying the mechanical stress–induced lung fibrosis and highlight potential therapeutic strategies to mitigate this fibrosis.

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.

Despite recent advances in the management of patients with acute respiratory distress syndrome (ARDS) by using protective ventilator strategies, the mortality rate of ARDS remains high. The complexity of the pathogenesis and the heterogeneity of coexisting diseases in patients with ARDS require critical care physicians and researchers to search for multiple therapeutic approaches in order to further improve patient outcome. This review article therefore focuses on the recent studies in the field of pharmacological intervention in ARDS.A number of approaches for pharmacological intervention have been evaluated in patients with ARDS, but most of them failed to reduce mortality or improve outcomes despite some promising observations seen in preclinical studies. Prior methods such as nitric oxide inhalation, neuromuscular blocking agents and corticosteroids may still have a place in the treatment, while novel therapeutic approaches including the use of angiotensin-converting enzyme inhibitors, statins and stem cells are currently under investigation.Overall, there is no proven pharmacological therapy in ARDS, but some pharmacological interventions were associated with beneficial effects in certain subgroups of patients depending on the cause, underlying diseases, the concurrent supportive therapies and timing. Further clinical trials are warranted to assess multiple outcome measurement of the promising pharmacological interventions in selected patients with ARDS.

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.

Survival from ARDS has increased substantially in the last twenty years as a result of key advances in lung-protective ventilation and resuscitation. Similarly, clinical practice improvements have contributed to an impressive decline in nosocomial ARDS incidence. Personalizing mechanical ventilation for further lung protection is a top research priority for the years ahead. However, the ARDS research agenda must be broader in scope. The clinical syndrome of ARDS includes a heterogeneous assemblage of pathophysiological processes leading to lung injury. Further understanding of these varied, complex biological underpinnings of ARDS pathogenesis is needed to inform therapeutic discovery and tailor management strategy to the individual patient. While some therapies may be applicable broadly to all ARDS patients, others may benefit only certain biologically distinct subsets. The twenty-year ARDSne(x)t research agenda calls for bringing personalized medicine to ARDS, asking simultaneously both whether a treatment affords clinically meaningful benefit and for whom. This expanded scope necessitates acquisition of highly granular biological, physiological, and clinical data as the new standard across studies. Tremendous investment in research infrastructure and global collaboration will be vital to fulfilling this agenda.

Purpose: Gamma-aminobutyric acid (GABA) is the major inhibitory neurotransmitter through activation of GABA receptors. Volatile anesthetics activate type-A (GABAA) receptors resulting in inhibition of synaptic transmission. Lung epithelial cells have been recently found to express GABAA receptors that exert anti-inflammatory properties. We hypothesized that the volatile anesthetic sevoflurane (SEVO) attenuates lung inflammation through activation of lung epithelial GABAA receptors. Methods: Sprague-Dawley rats were anesthetized with SEVO or ketamine/xylazine (KX). Acute lung inflammation was induced by intratracheal instillation of endotoxin, followed by mechanical ventilation for 4 h at a tidal volume of 15 mL/kg without positive end-expiratory pressure (two-hit lung injury model). To examine the specific effects of GABA, healthy human lung epithelial cells (BEAS-2B) were challenged with endotoxin in the presence and absence of GABA with and without addition of the GABAA receptor antagonist picrotoxin. Results: Anesthesia with SEVO improved oxygenation and reduced pulmonary cytokine responses compared to KX. This phenomenon was associated with increased expression of the π subunit of GABAA receptors and glutamic acid decarboxylase (GAD). The endotoxin-induced cytokine release from BEAS-2B cells was attenuated by the treatment with GABA, which was reversed by the administration of picrotoxin. Conclusion: Anesthesia with SEVO suppresses pulmonary inflammation and thus protects the lung from the two-hit injury. The anti-inflammatory effect of SEVO is likely due to activation of pulmonary GABAA signaling pathways.

Chronic obstructive pulmonary disease (COPD/pulmonary emphysema) is a common disease with a high incidence and a medico-economical impact which should not be underestimated. Pathophysiologically it is defined as expiratory obstruction due to increased airway resistance. The extensive comorbidity of COPD patients as well as the impairment of the respiratory system make COPD a key challenge for anesthesiologists. Besides basic drug therapy, differentiated ventilation support represents a hallmark of perioperative management. This article includes the current recommendations of the German national care guidelines for COPD as well as the COPD guidelines of the American Thoracic Society.

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.

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.

This educational narrative review provides a summary of non-ventilatory strategies to prevent postoperative pulmonary complications (PPCs). It highlights patient- and procedure-related risk factors for PPCs that are non-modifiable, potentially modifiable, or well modifiable. Non-ventilatory strategies, mainly based on the modification of risk factors, play a key role in reducing PPCs. Non-modifiable risk factors, most importantly age, American Society of Anesthesiologists (ASA) class, and risk of the procedure, should be recognized and patients intensively screened for the potential to optimize other, potentially or well-modifiable, risk factors. Potentially modifiable risk factors, mainly comorbidities and the surgical approach, increase the risk of PPCs. Patient-related factors can be improved while procedure-related factors may be adapted in high-risk patients. Well-modifiable risk factors, mainly certain anesthesia techniques, for example, general anesthesia, intravenous opioids or liberal fluid management, and smoking or alcohol abuse, should be avoided as far as possible in order to prevent PPCs.