SOLVe: a closed-loop system focused on protective mechanical ventilation.

BACKGROUND: Mechanical ventilation is an essential component in the treatment of patients with acute respiratory distress syndrome. Prompt adaptation of the settings of a ventilator to the variable needs of patients is essential to ensure personalised and protective ventilation. Still, it is challenging and time-consuming for the therapist at the bedside. In addition, general implementation barriers hinder the timely incorporation of new evidence from clinical studies into routine clinical practice. RESULTS: We present a system combing clinical evidence and expert knowledge within a physiological closed-loop control structure for mechanical ventilation. The system includes multiple controllers to support adequate gas exchange while adhering to multiple evidence-based components of lung protective ventilation. We performed a pilot study on three animals with an induced ARDS. The system achieved a time-in-target of over 75 % for all targets and avoided any critical phases of low oxygen saturation, despite provoked disturbances such as disconnections from the ventilator and positional changes of the subject. CONCLUSIONS: The presented system can provide personalised and lung-protective ventilation and reduce clinician workload in clinical practice.

Standardized High-Quality Processes for End-of-Life-Decision Making in the Intensive Care Unit Remain Robust during an Unprecedented New Pandemic-A Single-Center Experience.

Due to the global COVID-19 pandemic, a concomitant increase in awareness for end-of-life decisions (EOLDs) and advance care planning has been noted. Whether the dynamic pandemic situation impacted EOLD-processes on the intensive care unit (ICU) and patient-sided advance care planning in Germany is unknown. This is a retrospective analysis of all deceased patients of surgical ICUs of a university medical center from March 2020 to July 2021. All included ICUs had established standardized protocols and documentation for EOLD-related aspects of ICU therapy. The frequency of EOLDs and advance directives and the process of EOLDs were analyzed (No. of ethical approval EA2/308/20). A total number of 319 (85.5%) of all deceased patients received an EOLD. Advance directives were possessed by 83 (22.3%) of the patients and a precautionary power of attorney by 92 (24.7%) of the patients. There was no difference in the frequency of EOLDs and patient-sided advance care planning between patients with COVID-19 and non-COVID-19 patients. In addition, no differences in frequencies of do-not-resuscitate orders, withholding or withdrawing of intensive care medicine therapeutic approaches, timing of EOLDs, and participation of senior ICU attendings in EOLDs were noted between patients with COVID-19 and non-COVID-19 patients. Documentation of family conferences occurred more often in deceased patients with COVID-19 compared to non-COVID-19 patients (COVID-19: 80.0% vs. non-COVID-19: 56.8, p = 0.001). Frequency of EOLDs and completion rates of advance directives remained unchanged during the pandemic compared to pre-pandemic years. The EOLD process did not differ between patients with COVID-19 and non-COVID-19 patients. Institutional standard procedures might contribute to support the robustness of EOLD-making processes during unprecedented medical emergencies, such as new pandemic diseases.

Induction of severe hypoxemia and low lung recruitability for the evaluation of therapeutic ventilation strategies: a translational model of combined surfactant-depletion and ventilator-induced lung injury.

BACKGROUND: Models of hypoxemic lung injury caused by lavage-induced pulmonary surfactant depletion are prone to prompt recovery of blood oxygenation following recruitment maneuvers and have limited translational validity. We hypothesized that addition of injurious ventilation following surfactant-depletion creates a model of the acute respiratory distress syndrome (ARDS) with persistently low recruitability and higher levels of titrated "best" positive end-expiratory pressure (PEEP) during protective ventilation. METHODS: Two types of porcine lung injury were induced by lung lavage and 3 h of either protective or injurious ventilation, followed by 3 h of protective ventilation (N = 6 per group). Recruitment maneuvers (RM) and decremental PEEP trials comparing oxygenation versus dynamic compliance were performed after lavage and at 3 h intervals of ventilation. Pulmonary gas exchange function, respiratory mechanics, and ventilator-derived parameters were assessed after each RM to map the course of injury severity and recruitability. RESULTS: Lung lavage impaired respiratory system compliance (Crs) and produced arterial oxygen tensions (PaO2) of 84±13 and 80±15 (FIO2 = 1.0) with prompt increase after RM to 270-395 mmHg in both groups. After subsequent 3 h of either protective or injurious ventilation, PaO2/FIO2 was 104±26 vs. 154±123 and increased to 369±132 vs. 167±87 mmHg in response to RM, respectively. After additional 3 h of protective ventilation, PaO2/FIO2 was 120±15 vs. 128±37 and increased to 470±68 vs. 185±129 mmHg in response to RM, respectively. Subsequently, decremental PEEP titration revealed that Crs peaked at 36 ± 10 vs. 25 ± 5 ml/cm H2O with PEEP of 12 vs. 16 cmH2O, and PaO2/FIO2 peaked at 563 ± 83 vs. 334 ± 148 mm Hg with PEEP of 16 vs. 22 cmH2O in the protective vs. injurious ventilation groups, respectively. The large disparity of recruitability between groups was not reflected in the Crs nor the magnitude of mechanical power present after injurious ventilation, once protective ventilation was resumed. CONCLUSION: Addition of transitory injurious ventilation after lung lavage causes prolonged acute lung injury with diffuse alveolar damage and low recruitability yielding high titrated PEEP levels. Mimicking lung mechanical and functional characteristics of ARDS, this porcine model rectifies the constraints of single-hit lavage models and may enhance the translation of experimental research on mechanical ventilation strategies.

COVID-19 Patients Require Prolonged Extracorporeal Membrane Oxygenation Support for Survival Compared With Non-COVID-19 Patients.

To investigate the ICU survival of venovenous extracorporeal membrane oxygenation (ECMO) patients suffering from COVID-19-related acute respiratory distress syndrome (ARDS) versus ECMO patients without COVID-19 (non-COVID-19)-related ARDS. DESIGN: Preliminary analysis of data from two prospective ECMO trials and retrospective analysis of a cohort of ARDS ECMO patients. SETTING: Single-center ICU. PATIENTS: Adult ARDS ECMO patients, 16 COVID-19 versus 23 non-COVID-19 patients. Analysis of retrospective data from 346 adult ARDS ECMO patients. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: COVID-19 and non-COVID-19 ARDS patients did not differ with respect to preexisting disease or body mass index. ICU survival rate was 62% for COVID-19 ECMO patients and 70% for non-COVID-19 ECMO patients. COVID-19 ECMO survivors were supported with ECMO for a median of 43 days (interquartile range [IQR], 18-58 d) versus 16 days (IQR, 19-39 d; p = 0.03) for non-COVID-19 patients. The median duration of ECMO therapy for all ARDS patients between 2007 and 2018 was 15 days (IQR, 6-28 d). The subgroup of patients suffering from any viral pneumonia received ECMO support for a median of 16 days (IQR, 9-27 d), survivors of influenza pneumonia received ECMO support for 13 days (IQR, 7-25 d). CONCLUSIONS: COVID-19 patients required significant longer ECMO support compared with patients without COVID-19 to achieve successful ECMO weaning and ICU survival.

Age of Red Cells for Transfusion and Outcomes in Patients with ARDS.

Packed red blood cells (PRBCs), stored for prolonged intervals, might contribute to adverse clinical outcomes in critically ill patients. In this study, short-term outcome after transfusion of PRBCs of two storage duration periods was analyzed in patients with Acute Respiratory Distress Syndrome (ARDS). Patients who received transfusions of PRBCs were identified from a cohort of 1044 ARDS patients. Patients were grouped according to the mean storage age of all transfused units. Patients transfused with PRBCs of a mean storage age ≤ 28 days were compared to patients transfused with PRBCs of a mean storage age > 28 days. The primary endpoint was 28-day mortality. Secondary endpoints included failure-free days composites. Two hundred and eighty-three patients were eligible for analysis. Patients in the short-term storage group had similar baseline characteristics and received a similar amount of PRBC units compared with patients in the long-term storage group (five units (IQR, 3-10) vs. four units (2-8), p = 0.14). The mean storage age in the short-term storage group was 20 (±5.4) days compared with 32 (±3.1) days in the long-term storage group (mean difference 12 days (95%-CI, 11-13)). There was no difference in 28-day mortality between the short-term storage group compared with the long-term storage group (hazard ratio, 1.36 (95%-CI, 0.84-2.21), p = 0.21). While there were no differences in ventilator-free, sedation-free, and vasopressor-free days composites, patients in the long-term storage group compared with patients in the short-term storage group had a 75% lower chance for successful weaning from renal replacement therapy (RRT) within 28 days after ARDS onset (subdistribution hazard ratio, 0.24 (95%-CI, 0.1-0.55), p < 0.001). Further analysis indicated that even a single PRBC unit stored for more than 28 days decreased the chance for successful weaning from RRT. Prolonged storage of PRBCs was not associated with a higher mortality in adults with ARDS. However, transfusion of long-term stored PRBCs was associated with prolonged dependence of RRT in critically ill patients with an ARDS.

Extracorporeal Membrane Oxygenation Blood Flow and Blood Recirculation Compromise Thermodilution-Based Measurements of Cardiac Output.

The contribution of veno-venous (VV) extracorporeal membrane oxygenation (ECMO) to systemic oxygen delivery is determined by the ratio of total extracorporeal blood flow () to cardiac output (). Thermodilution-based measurements of may be compromised by blood recirculating through the ECMO (recirculation fraction; Rf). We measured the effects of and Rf on classic thermodilution-based measurements of in six anesthetized pigs. An ultrasound flow probe measured total aortic blood flow () at the aortic root. Rf was quantified with the ultrasound dilution technique. was set to 0-125% of and was measured using a pulmonary artery catheter (PAC) in healthy and lung injured animals. PAC overestimated () at all settings compared to . The mean bias between both methods was 2.1 L/min in healthy animals and 2.7 L/min after lung injury. The difference between and increased with an of 75-125%/ compared to QEC <50%/. Overestimation of was highest when resulted in a high Rf. Thus, thermodilution-based measurements can overestimate cardiac output during VV ECMO. The degree of overestimation of depends on the EC/ ratio and the recirculation fraction.

In vitro validation and characterization of pulsed inhaled nitric oxide administration during early inspiration.

PURPOSE: Admixture of nitric oxide (NO) to the gas inspired with mechanical ventilation can be achieved through continuous, timed, or pulsed injection of NO into the inspiratory limb. The dose and timing of NO injection govern the inspired and intrapulmonary effect site concentrations achieved with different administration modes. Here we test the effectiveness and target reliability of a new mode injecting pulsed NO boluses exclusively during early inspiration. METHODS: An in vitro lung model was operated under various ventilator settings. Admixture of NO through injection into the inspiratory limb was timed either (i) selectively during early inspiration ("pulsed delivery"), or as customary, (ii) during inspiratory time or (iii) the entire respiratory cycle. Set NO target concentrations of 5-40 parts per million (ppm) were tested for agreement with the yield NO concentrations measured at various sites in the inspiratory limb, to assess the effectiveness of these NO administration modes. RESULTS: Pulsed delivery produced inspiratory NO concentrations comparable with those of customary modes of NO administration. At low (450 ml) and ultra-low (230 ml) tidal volumes, pulsed delivery yielded better agreement of the set target (up to 40 ppm) and inspiratory NO concentrations as compared to customary modes. Pulsed delivery with NO injection close to the artificial lung yielded higher intrapulmonary NO concentrations than with NO injection close to the ventilator. The maximum inspiratory NO concentration observed in the trachea (68 ± 30 ppm) occurred with pulsed delivery at a set target of 40 ppm. CONCLUSION: Pulsed early inspiratory phase NO injection is as effective as continuous or non-selective admixture of NO to inspired gas and may confer improved target reliability, especially at low, lung protective tidal volumes.

End-of-Life Decision-Making in Intensive Care Ten Years after a Law on Advance Directives in Germany.

Background and Objectives: Mortality on Intensive Care Units (ICUs) is high and death frequently occurs after decisions to limit life-sustaining therapies. An advance directive is a tool meant to preserve patient autonomy by guiding anticipated future treatment decisions once decision-making capacity is lost. Since September 2009, advance directives are legally binding for the caregiver team and the patients' surrogate decision-maker in Germany. The change in frequencies of end-of-life decisions (EOLDs) and completed advance directives among deceased ICU patients ten years after the enactment of a law on advance directives in Germany is unknown. Materials and Methods: Retrospective analysis on all deceased patients of surgical ICUs of a German university medical center from 08/2008 to 09/2009 and from 01/2019 to 09/2019. Frequency of EOLDs and advance directives and the process of EOLDs were compared between patients admitted before and after the change in legislation. (No. of ethical approval EA2/308/20) Results: Significantly more EOLDs occurred in the 2019 cohort compared to the 2009 cohort (85.8% vs. 70.7% of deceased patients, p = 0.006). The number of patients possessing an advance directive to express a living or therapeutic will was higher in the 2019 cohort compared to the 2009 cohort (26.4% vs. 8.9%; difference: 17.5%, p < 0.001). Participation of the patients' family in the EOLD process (74.7% vs. 60.9%; difference: 13.8%, p = 0.048) and the frequency of documentation of EOLD-relevant information (50.0% vs. 18.7%; difference: 31.3%, p < 0.001) increased from 2009 to 2019. Discussion: During a ten-year period from 2009 to 2019, the frequency of EOLDs and the completion rate of advance directives have increased considerably. In addition, EOLD-associated communication and documentation have further improved.

Surfactant Depletion Combined with Injurious Ventilation Results in a Reproducible Model of the Acute Respiratory Distress Syndrome (ARDS).

Various animal models exist to study the complex pathomechanisms of the acute respiratory distress syndrome (ARDS). These models include pulmo-arterial infusion of oleic acid, infusion of endotoxins or bacteria, cecal ligation and puncture, various pneumonia models, lung ischemia/reperfusion models and, of course, surfactant depletion models, among others. Surfactant depletion produces a rapid, reproducible deterioration of pulmonary gas exchange and hemodynamics and can be induced in anesthetized pigs using repeated lung lavages with 0.9% saline (35 mL/kg body weight, 37 °C). The surfactant depletion model supports investigations with standard respiratory and hemodynamic monitoring with clinically applied devices. But the model suffers from a relatively high recruitability and ventilation with high airway pressures can immediately reduce the severity of the injury by reopening atelectatic lung areas. Thus, this model is not suitable for investigations of ventilator regimes that use high airway pressures. A combination of surfactant depletion and injurious ventilation with high tidal volume/low positive end-expiratory pressure (high Tv/low PEEP) to cause ventilator induced lung injury (VILI) will reduce the recruitability of the resulting lung injury. The advantages of a timely induction and the possibility to perform experimental research in a setting comparable to an intensive care unit are preserved.

Tert-butylhydroquinone augments Nrf2-dependent resilience against oxidative stress and improves survival of ventilator-induced lung injury in mice.

Oxidative stress caused by mechanical ventilation contributes to the pathophysiology of ventilator-induced lung injury (VILI). A key mechanism maintaining redox balance is the upregulation of nuclear factor-erythroid-2-related factor 2 (Nrf2)-dependent antioxidant gene expression. We tested whether pretreatment with an Nrf2-antioxidant response element (ARE) pathway activator tert-butylhydroquinone (tBHQ) protects against VILI. Male C57BL/6J mice were pretreated with an intraperitoneal injection of tBHQ (n = 10), an equivalent volume of 3% ethanol (EtOH3%, vehicle, n = 13), or phosphate-buffered saline (controls, n = 10) and were then subjected to high tidal volume (HVT) ventilation for a maximum of 4 h. HVT ventilation severely impaired arterial oxygenation ([Formula: see text] = 49 ± 7 mmHg, means ± SD) and respiratory system compliance, resulting in a 100% mortality among controls. Compared with controls, tBHQ improved arterial oxygenation ([Formula: see text] = 90 ± 41 mmHg) and respiratory system compliance after HVT ventilation. In addition, tBHQ attenuated the HVT ventilation-induced development of lung edema and proinflammatory response, evidenced by lower concentrations of protein and proinflammatory cytokines (IL-1ß and TNF-α) in the bronchoalveolar lavage fluid, respectively. Moreover, tBHQ enhanced the pulmonary redox capacity, indicated by enhanced Nrf2-depentent gene expression at baseline and by the highest total glutathione concentration after HVT ventilation among all groups. Overall, tBHQ pretreatment resulted in 60% survival (P < 0.001 vs. controls). Interestingly, compared with controls, EtOH3% reduced the proinflammatory response to HVT ventilation in the lung, resulting in 38.5% survival (P = 0.0054 vs. controls). In this murine model of VILI, tBHQ increases the pulmonary redox capacity by activating the Nrf2-ARE pathway and protects against VILI. These findings support the efficacy of pharmacological Nrf2-ARE pathway activation to increase resilience against oxidative stress during injurious mechanical ventilation.

Point-of-Care diagnostics of coagulation in the management of bleeding and transfusion in trauma patients.

PURPOSE OF REVIEW: Trauma-associated bleeding and coagulopathy require timely identification, prevention, and effective treatment. The present review summarizes the recent literature around point-of-care (POC) coagulation tests, their usefulness in the management of trauma-induced coagulopathy (TIC), their impact on trauma patient outcomes, and the requirement of quality assurance. RECENT FINDINGS: Best practice algorithms to manage TIC have been compiled in the 2019 European Guideline on the management of major bleeding and coagulopathy after trauma. Evidence supports the use of goal-directed approaches to manage TIC. POC coagulation tests can accelerate and tailor individualized therapies. Recent findings emphasize: the time sparing of POC tests in prehospital settings and the validity of POC measurements in extreme environments; the potential scalability of POC-guided TIC algorithms in burn injuries and the pediatric population; the need for careful considerations of strategies to monitor and reverse the effects of direct oral anticoagulants in major trauma. SUMMARY: In contrast to an abundance of reviews and practical approaches to POC coagulation management in trauma patients, there is a scarcity of research in the field and large-scale clinical trials are urgently needed. The paneuropean multicenter trial Implementing Treatment Algorithms for the Correction of Trauma Induced Coagulopathy (iTACTIC) will inform on the potential of viscoelastic tests to augment transfusion protocols for better patient outcomes.

Routine frailty assessment predicts postoperative complications in elderly patients across surgical disciplines - a retrospective observational study.

BACKGROUND: Frailty is a frequent and underdiagnosed functional syndrome involving reduced physiological reserves and an increased vulnerability against stressors, with severe individual and socioeconomic consequences. A routine frailty assessment was implemented at our preoperative anaesthesia clinic to identify patients at risk. OBJECTIVE: This study examines the relationship between frailty status and the incidence of in-hospital postoperative complications in elderly surgical patients across several surgical disciplines. DESIGN: Retrospective observational analysis. SETTING: Single center, major tertiary care university hospital. Data collection took place between June 2016 and March 2017. PATIENTS: Patients 65 years old or older were evaluated for frailty using Fried's 5-point frailty assessment prior to elective non-cardiac surgery. Patients were classified into non-frail (0 criteria, reference group), pre-frail (1-2 positive criteria) and frail (3-5 positive criteria) groups. MAIN OUTCOME MEASURES: The incidence of postoperative complications was assessed until discharge from the hospital, using the roster from the National VA Surgical Quality Improvement Program. Propensity score matching and logistic regression analysis were performed. RESULTS: From 1186 elderly patients, 46.9% were classified as pre-frail (n = 556), and 11.4% as frail (n = 135). The rate of complications were significantly higher in the pre-frail (34.7%) and frail groups (47.4%), as compared to the non-frail group (27.5%). Similarly, length of stay (non-frail: 5.0 [3.0;7.0], pre-frail: 7.0 [3.0;9.0], frail 8.0 [4.5;12.0]; p < 0.001) and discharges to care facilities (non-frail:1.6%, pre-frail: 7.4%, frail: 17.8%); p < 0.001) were significantly associated with frailty status. After propensity score matching and logistic regression analysis, the risk for developing postoperative complications was approximately two-fold for pre-frail (OR 1.78; 95% CI 1.04-3.05) and frail (OR 2.08; 95% CI 1.21-3.60) patients. CONCLUSIONS: The preoperative frailty assessment of elderly patients identified pre-frail and frail subgroups to have the highest rate of postoperative complications, regardless of age, surgical discipline, and surgical risk. Significantly increased length of hospitalisation and discharges to care facilities were also observed. Implementation of routine frailty assessments appear to be an effective tool in identifying patients with increased risk. Now future studies are needed to investigate whether patients benefit from optimization of patient counselling, process planning, and risk reduction protocols based on the application of risk stratification.

Lung Purinoceptor Activation Triggers Ventilator-Induced Brain Injury.

OBJECTIVES: Mechanical ventilation can cause ventilator-induced brain injury via afferent vagal signaling and hippocampal neurotransmitter imbalances. The triggering mechanisms for vagal signaling during mechanical ventilation are unknown. The objective of this study was to assess whether pulmonary transient receptor potential vanilloid type-4 (TRPV4) mechanoreceptors and vagal afferent purinergic receptors (P2X) act as triggers of ventilator-induced brain injury. DESIGN: Controlled, human in vitro and ex vivo studies, as well as murine in vivo laboratory studies. SETTING: Research laboratory. SUBJECTS: Wild-type, TRPV4-deficient C57BL/6J mice, 8-10 weeks old. Human postmortem lung tissue and human lung epithelial cell line BEAS-2B. INTERVENTION: Mice subjected to mechanical ventilation were studied using functional MRI to assess hippocampal activity. The effects of lidocaine (a nonselective ion-channel inhibitor), P2X-purinoceptor antagonist (iso-PPADS), or genetic TRPV4 deficiency on hippocampal dopamine-dependent pro-apoptotic signaling were studied in mechanically ventilated mice. Human lung epithelial cells (BEAS-2B) were used to study the effects of mechanical stretch on TRPV4 and P2X expression and activation. TRPV4 levels were measured in postmortem lung tissue from ventilated and nonventilated patients. MEASUREMENTS AND MAIN RESULTS: Hippocampus functional MRI analysis revealed considerable changes in response to the increase in tidal volume during mechanical ventilation. Intratracheal lidocaine, iso-PPADS, and TRPV4 genetic deficiency protected mice against ventilationinduced hippocampal pro-apoptotic signaling. Mechanical stretch in both, BEAS-2B cells and ventilated wild-type mice, resulted in TRPV4 activation and reduced Trpv4 and P2x expression. Intratracheal replenishment of adenosine triphosphate in Trpv4 mice abrogated the protective effect of TRPV4 deficiency. Autopsy lung tissue from ventilated patients showed decreased lung TRPV4 levels compared with nonventilated CONCLUSIONS:: TRPV4 mechanosensors and purinergic receptors are involved in the mechanisms of ventilator-induced brain injury. Inhibition of this neural signaling, either using nonspecific or specific inhibitors targeting the TRPV4/adenosine triphosphate/P2X signaling axis, may represent a novel strategy to prevent or treat ventilator-induced brain injury.

Carbonic anhydrase is not a relevant nitrite reductase or nitrous anhydrase in the lung.

KEY POINTS: Carbonic anhydrase (CA) inhibitors such as acetazolamide inhibit hypoxic pulmonary vasoconstriction (HPV) in humans and other mammals, but the mechanism of this action remains unknown. It has been postulated that carbonic anhydrase may act as a nitrous anhydrase in vivo to generate nitric oxide (NO) from nitrite and that this formation is increased in the presence of acetazolamide. Acetazolamide reduces HPV in pigs without evidence of any NO generation, whereas nebulized sodium nitrite reduces HPV by NO formation; however; combined infusion of acetazolamide with sodium nitrite inhalation did not further increase exhaled NO concentration over inhaled nitrite alone in pigs exposed to alveolar hypoxia. We conclude that acetazolamide does not function as either a nitrous anhydrase or a nitrite reductase in the lungs of pigs, and probably other mammals, to explain its vasodilating actions in the pulmonary or systemic circulations. ABSTRACT: The carbonic anhydrase (CA) inhibitors acetazolamide and its structurally similar analogue methazolamide prevent or reduce hypoxic pulmonary vasoconstriction (HPV) in dogs and humans in vivo, by a mechanism unrelated to CA inhibition. In rodent blood and isolated blood vessels, it has been reported that inhibition of CA leads to increased generation of nitric oxide (NO) from nitrite and vascular relaxation in vitro. We tested the physiological relevance of augmented NO generation by CA from nitrite with acetazolamide in anaesthetized pigs during alveolar hypoxia in vivo. We found that acetazolamide prevents HPV in anaesthetized pigs, as in other mammalian species. A single nebulization of sodium nitrite reduces HPV, but this action wanes in the succeeding 3 h of hypoxia as nitrite is metabolized and excreted. Pulmonary artery pressure reduction and NO formation as measured by exhaled gas concentration from inhaled sodium nitrite were not increased by acetazolamide during alveolar hypoxia. Thus, our data argue against a physiological role of carbonic anhydrase as a nitrous anhydrase or nitrite reductase as a mechanism for its inhibition of HPV in the lung and blood in vivo.

[Management of Pediatric Airway in Anesthesia]. / Atemwegsmanagement in der Kinderanästhesie: Anwendung von Materialien und Methoden.

Airway management is a major competence of clinical anesthesia. Knowledge of available materials and skills in the use of specific methods and techniques are essential and should be trained routinely. In 2011 the scientific working group in pediatric anesthesia (WAKKA) of the German Society for anesthesia and intensive care medicine (DGAI) published a treatment recommendation for the management of the unexpected difficult pediatric airway. Furthermore, a recommendation for the management of the expected difficult pediatric airway is currently being compiled and the draft is available on the WAKKA homepage. For the airway management in pediatric patients, special materials, techniques, individual and institutional expertise must be present. This article presents a selection of materials, methods and techniques of the treatment recommendations for the management of a difficult airway.

[The Relevance of Hemolysis in Anesthesia and Intensive Care Medicine]. / Die Bedeutung der Hämolyse in Anästhesie und Intensivmedizin.

Hemolysis leads to an increase of circulating intravascular cell-free hemoglobin. Increased plasma concentrations of cell-free hemoglobin are relevant in critically ill patients because cell-free hemoglobin causes vasoconstriction by depletion of endothelial nitric oxide, oxidative stress, and inflammation. Furthermore, cell-free hemoglobin contributes to tissue injuries such as renal failure and intestinal mucosa damage after cardiac surgery. High concentrations of cell-free hemoglobin are associated with an increased mortality in patients with sepsis. Currently, it is unclear if hemolysis associated with transfusion of packed red blood cells that have been stored for prolonged periods of time is relevant for the clinical outcome. However, humans possess plasma proteins haptoglobin and hemopexin which bind to plasma hemoglobin and cell-free heme, respectively. The haptoglobin-hemoglobin and hemopexin-heme complexes are then eliminated from the plasma by hepatic or splenic uptake.

Closed-loop mechanical ventilation for lung injury: a novel physiological-feedback mode following the principles of the open lung concept.

Adherence to low tidal volume (VT) ventilation and selected positive end-expiratory pressures are low during mechanical ventilation for treatment of the acute respiratory distress syndrome. Using a pig model of severe lung injury, we tested the feasibility and physiological responses to a novel fully closed-loop mechanical ventilation algorithm based on the "open lung" concept. Lung injury was induced by surfactant washout in pigs (n = 8). Animals were ventilated following the principles of the "open lung approach" (OLA) using a fully closed-loop physiological feedback algorithm for mechanical ventilation. Standard gas exchange, respiratory- and hemodynamic parameters were measured. Electrical impedance tomography was used to quantify regional ventilation distribution during mechanical ventilation. Automatized mechanical ventilation provided strict adherence to low VT-ventilation for 6 h in severely lung injured pigs. Using the "open lung" approach, tidal volume delivery required low lung distending pressures, increased recruitment and ventilation of dorsal lung regions and improved arterial blood oxygenation. Physiological feedback closed-loop mechanical ventilation according to the principles of the open lung concept is feasible and provides low tidal volume ventilation without human intervention. Of importance, the "open lung approach"-ventilation improved gas exchange and reduced lung driving pressures by opening atelectasis and shifting of ventilation to dorsal lung regions.