Improved ventilation efficiency due to continuous gas flow compared to decelerating gas flow in mechanical ventilation: results of a porcine trial.

In pressure-controlled ventilation (PCV), a decelerating gas flow pattern occurs during inspiration and expiration. In contrast, flow-controlled ventilation (FCV) guarantees a continuous gas flow throughout the entire ventilation cycle where the inspiration and expiration phases are simply performed by a change of gas flow direction. The aim of this trial was to highlight the effects of different flow patterns on respiratory variables and gas exchange. Anesthetized pigs were ventilated with either FCV or PCV for 1 h and thereafter for 30 min each in a crossover comparison. Both ventilation modes were set with a peak pressure of 15 cmH2O, positive end-expiratory pressure of 5 cmH2O, a respiratory rate of 20/min, and a fraction of inspired oxygen at 0.3. All respiratory variables were collected every 15 min. Tidal volume and respiratory minute volume were significantly lower in FCV (n = 5) compared with PCV (n = 5) animals [4.6 vs. 6.6, MD -2.0 (95% CI -2.6 to -1.4) mL/kg; P < 0.001 and 7.3 vs. 9.5, MD -2.2 (95% CI -3.3 to -1.0) L/min; P = 0.006]. Notwithstanding these differences, CO2-removal as well as oxygenation was not inferior in FCV compared with PCV. Mechanical ventilation with identical ventilator settings resulted in lower tidal volumes and consecutive minute volume in FCV compared with PCV. This finding can be explained physically by the continuous gas flow pattern in FCV that necessitates a lower alveolar pressure amplitude. Interestingly, gas exchange was comparable in both groups, which is suggestive of improved ventilation efficiency at a continuous gas flow pattern.NEW & NOTEWORTHY This study examined the effects of a continuous (flow-controlled ventilation, FCV) vs. decelerating (pressure-controlled ventilation, PCV) gas flow pattern during mechanical ventilation. It was shown that FCV necessitates a lower alveolar pressure amplitude leading to reduced applied tidal volumes and consequently minute volume. Notwithstanding these differences, CO2-removal as well as oxygenation was not inferior in FCV compared with PCV, which is suggestive of improved gas exchange efficiency at a continuous gas flow pattern.

COVID-19 Pandemic Did not Influence Number of Oncologic and Emergency Surgeries: A Retrospective Cohort Study from a Tertiary Hospital in Austria.

BACKGROUND: Many articles described a massive decline in surgical procedures during the COVID-19 pandemic waves. Especially the reduction in oncologic and emergency procedures led to the concern that delays and cancelling surgical activity might lead to a substantial increase in preventable deaths. METHODS: Overall numbers and types of surgery were analysed in a tertiary hospital in Austria during the winter period (October-April) from 2015/16 to 2021/22. The half-years 2019/20, 2020/21 and 2021/22 were defined as pandemic half-years and were compared with the mean results of the previous, four, pre-pandemic half-years. RESULTS: A reduction was found for overall numbers and elective surgeries during 2019/20 (4.62%; p < 0.0001 and 12.14; p < 0.0001 respectively) and 2021/22 (14.94%; p < 0.0001 and 34.27; p < 0.0001 respectively). Oncologic surgery increased during 2021/22 (- 12.59%; p < 0.0001) and remained unchanged during the other periods. Emergency surgeries increased during 2019/20 (- 6.97%; p < 0.0001) and during 2021/22 (- 9.44%; p < 0.0001) and remained unchanged during 2020/21. CONCLUSIONS: The concern that the pandemic led to a decrease in oncologic and emergency surgeries cannot be supported with the data from our hospital. A flexible, day-by-day, resource allocation programme with central coordination adhering to hospital resilience recommendations may have helped to adapt to the impact of the COVID-19 pandemic during the first three pandemic half-years.

Individualised flow-controlled versus pressure-controlled ventilation in a porcine oleic acid-induced acute respiratory distress syndrome model.

BACKGROUND: A continuous gas flow provided by flow-controlled ventilation (FCV) facilitates accurate dynamic compliance measurement and allows the clinician to individually optimise positive end-expiratory and peak pressure settings accordingly. OBJECTIVE: The aim of this study was to compare the efficiency of gas exchange and impact on haemodynamics between individualised FCV and pressure-controlled ventilation (PCV) in a porcine model of oleic acid-induced acute respiratory distress syndrome (ARDS). DESIGN: Randomised controlled interventional trial conducted on 16 pigs. SETTING: Animal operating facility at the Medical University Innsbruck. INTERVENTIONS: ARDS was induced in lung healthy pigs by intravenous infusion of oleic acid until moderate-to-severe ARDS at a stable Horowitz quotient (PaO 2 FiO 2-1 ) of 80 to 120 over a period of 30 min was obtained. Ventilation was then either performed with individualised FCV ( n  = 8) established by compliance-guided pressure titration or PCV ( n  = 8) with compliance-guided titration of the positive end-expiratory pressure and peak pressure set to achieve a tidal volume of 6 ml kg -1 over a period of 2 h. MAIN OUTCOME MEASURES: Gas exchange parameters were assessed by the PaO 2 FiO 2-1 quotient and CO 2 removal by the PaCO 2 value in relation to required respiratory minute volume. Required catecholamine support for haemodynamic stabilisation was measured. RESULTS: The FCV group showed significantly improved oxygenation [149.2 vs. 110.4, median difference (MD) 38.7 (8.0 to 69.5) PaO 2 FiO 2-1 ; P  = 0.027] and CO 2 removal [PaCO 2 7.25 vs. 9.05, MD -1.8 (-2.87 to -0.72) kPa; P  = 0.006] at a significantly lower respiratory minute volume [8.4 vs. 11.9, MD -3.6 (-5.6 to -1.5) l min -1 ; P  = 0.005] compared with PCV. In addition, in FCV-pigs, haemodynamic stabilisation occurred with a significant reduction of required catecholamine support [norepinephrine 0.26 vs. 0.86, MD -0.61 (-1.12 to -0.09) µg kg -1  min -1 ; P  = 0.037] during 2 ventilation hours. CONCLUSION: In this oleic acid-induced porcine ARDS model, individualised FCV significantly improved gas exchange and haemodynamic stability compared with PCV. TRIAL REGISTRATION: Protocol no.: BMBWF-66.011/0105-V/3b/2019).

Individualised flow-controlled ventilation versus pressure-controlled ventilation in a porcine model of thoracic surgery requiring one-lung ventilation: A laboratory study.

BACKGROUND: Flow-controlled ventilation (FCV) enables precise determination of dynamic compliance due to a continuous flow coupled with direct tracheal pressure measurement. Thus, pressure settings can be adjusted accordingly in an individualised approach. OBJECTIVE: The aim of this study was to compare gas exchange of individualised FCV to pressure-controlled ventilation (PCV) in a porcine model of simulated thoracic surgery requiring one-lung ventilation (OLV). DESIGN: Controlled interventional trial conducted on 16 domestic pigs. SETTING: Animal operating facility at the Medical University of Innsbruck. INTERVENTIONS: Thoracic surgery was simulated with left-sided thoracotomy and subsequent collapse of the lung over a period of three hours. When using FCV, ventilation was performed with compliance-guided pressure settings. When using PCV, end-expiratory pressure was adapted to achieve best compliance with peak pressure adjusted to achieve a tidal volume of 6 ml kg -1 during OLV. MAIN OUTCOME MEASURES: Gas exchange was assessed by the Horowitz index (= P aO 2 /FIO 2 ) and CO 2 removal by the P aCO 2 value in relation to required respiratory minute volume. RESULTS: In the FCV group ( n  = 8) normocapnia could be maintained throughout the OLV trial despite a significantly lower respiratory minute volume compared to the PCV group ( n  = 8) (8.0 vs. 11.6, 95% confidence interval, CI -4.5 to -2.7 l min -1 ; P  < 0.001), whereas permissive hypercapnia had to be accepted in PCV ( P aCO 2 5.68 vs. 6.89, 95% CI -1.7 to -0.7 kPa; P  < 0.001). The Horowitz index was comparable in both groups but calculated mechanical power was significantly lower in FCV (7.5 vs. 22.0, 95% CI -17.2 to -11.8 J min -1 ; P  < 0.001). CONCLUSIONS: In this porcine study FCV maintained normocapnia during OLV, whereas permissive hypercapnia had to be accepted in PCV despite a substantially higher minute volume. Reducing exposure of the lungs to mechanical power applied by the ventilator in FCV offers a possible advantage for this mode of ventilation in terms of lung protection.

A case report of individualized ventilation in a COVID-19 patient - new possibilities and caveats to consider with flow-controlled ventilation.

BACKGROUND: Flow-controlled ventilation (FCV) is a novel ventilation method increasingly being used clinically, particularly during the current COVID-19 pandemic. However, the continuous flow pattern in FCV during inspiration and expiration has a significant impact on respiratory parameters and ventilatory settings compared to conventional ventilation modes. In addition, the constant flow combined with direct intratracheal pressure measurement allows determination of dynamic compliance and ventilation settings can be adjusted accordingly, reflecting a personalized ventilation approach. CASE PRESENTATION: A 50-year old women with confirmed SARS-CoV-2 infection suffering from acute respiratory distress syndrome (ARDS) was admitted to a tertiary medical center. Initial ventilation occurred with best standard of care pressure-controlled ventilation (PCV) and was then switched to FCV, by adopting PCV ventilator settings. This led to an increase in oxygenation by 30 %. Subsequently, to reduce invasiveness of mechanical ventilation, FCV was individualized by dynamic compliance guided adjustment of both, positive end-expiratory pressure and peak pressure; this intervention reduced driving pressure from 18 to 12 cm H2O. However, after several hours, compliance further deteriorated which resulted in a tidal volume of only 4.7 ml/kg. CONCLUSIONS: An individualized FCV approach increased oxygenation parameters in a patient suffering from severe COVID-19 related ARDS. Direct intratracheal pressure measurements allow for determination of dynamic compliance and thus optimization of ventilator settings, thereby reducing applied and dissipated energy. However, although desirable, this personalized ventilation strategy may reach its limits when lung function is so severely impaired that patient's oxygenation has to be ensured at the expense of lung protective ventilation concepts.

The Endothelial Glycocalyx and Organ Preservation-From Physiology to Possible Clinical Implications for Solid Organ Transplantation.

The endothelial glycocalyx is a thin layer consisting of proteoglycans, glycoproteins and glycosaminoglycans that lines the luminal side of vascular endothelial cells. It acts as a barrier and contributes to the maintenance of vascular homeostasis and microperfusion. During solid organ transplantation, the endothelial glycocalyx of the graft is damaged as part of Ischemia Reperfusion Injury (IRI), which is associated with impaired organ function. Although several substances are known to mitigate glycocalyx damage, it has not been possible to use these substances during graft storage on ice. Normothermic machine perfusion (NMP) emerges as an alternative technology for organ preservation and allows for organ evaluation, but also offers the possibility to treat and thus improve organ quality during storage. This review highlights the current knowledge on glycocalyx injury during organ transplantation, presents ways to protect the endothelial glycocalyx and discusses potential glycocalyx protection strategies during normothermic machine perfusion.

Individualized flow-controlled ventilation compared to best clinical practice pressure-controlled ventilation: a prospective randomized porcine study.

BACKGROUND: Flow-controlled ventilation is a novel ventilation method which allows to individualize ventilation according to dynamic lung mechanic limits based on direct tracheal pressure measurement at a stable constant gas flow during inspiration and expiration. The aim of this porcine study was to compare individualized flow-controlled ventilation (FCV) and current guideline-conform pressure-controlled ventilation (PCV) in long-term ventilation. METHODS: Anesthetized pigs were ventilated with either FCV or PCV over a period of 10 h with a fixed FiO2 of 0.3. FCV settings were individualized by compliance-guided positive end-expiratory pressure (PEEP) and peak pressure (Ppeak) titration. Flow was adjusted to maintain normocapnia and the inspiration to expiration ratio (I:E ratio) was set at 1:1. PCV was performed with a PEEP of 5 cm H2O and Ppeak was set to achieve a tidal volume (VT) of 7 ml/kg. The respiratory rate was adjusted to maintain normocapnia and the I:E ratio was set at 1:1.5. Repeated measurements during observation period were assessed by linear mixed-effects model. RESULTS: In FCV (n = 6), respiratory minute volume was significantly reduced (6.0 vs 12.7, MD - 6.8 (- 8.2 to - 5.4) l/min; p < 0.001) as compared to PCV (n = 6). Oxygenation was improved in the FCV group (paO2 119.8 vs 96.6, MD 23.2 (9.0 to 37.5) Torr; 15.97 vs 12.87, MD 3.10 (1.19 to 5.00) kPa; p = 0.010) and CO2 removal was more efficient (paCO2 40.1 vs 44.9, MD - 4.7 (- 7.4 to - 2.0) Torr; 5.35 vs 5.98, MD - 0.63 (- 0.99 to - 0.27) kPa; p = 0.006). Ppeak and driving pressure were comparable in both groups, whereas PEEP was significantly lower in FCV (p = 0.002). Computed tomography revealed a significant reduction in non-aerated lung tissue in individualized FCV (p = 0.026) and no significant difference in overdistended lung tissue, although a significantly higher VT was applied (8.2 vs 7.6, MD 0.7 (0.2 to 1.2) ml/kg; p = 0.025). CONCLUSION: Our long-term ventilation study demonstrates the applicability of a compliance-guided individualization of FCV settings, which resulted in significantly improved gas exchange and lung tissue aeration without signs of overinflation as compared to best clinical practice PCV.

Shiga toxin 2a binds antithrombin and heparin, but does not directly activate platelets.

Escherichia coli-induced hemolytic uremic syndrome (eHUS) is a life-threatening complication of infection with Shiga toxin (Stx), in particular Stx2a-producing Escherichia coli. Enhanced coagulation activation with formation of microthrombi seems to be a key event in development of eHUS. Platelet activation has been postulated as a possible, but controversially debated mechanism. The present study investigated the effect of Stx2a on plasmatic coagulation and platelets. Binding studies were initially performed with ELISA and co-immunoprecipitation and supported by quartz crystal microbalance with dissipation monitoring (QCM-D). Antithrombin (AT) activity was measured using the automated BCS XP® system. ROTEM® was used for functional coagulation testing. Platelet binding and activation was studied with FACS and light-transmission aggregometry. We found binding of Stx2a to AT, an important inhibitor of blood coagulation, but only a mild albeit significant reduction of AT activity against FXa in the presence of Stx2a. QCM-D analysis also showed binding of Stx2a to heparin and an impaired binding of AT to Stx2a-bound heparin. ROTEM® using Stx2a-treated platelet-poor plasma revealed a significant, but only moderate shortening of clotting time. Neither binding nor activation of platelets by Stx2a could be demonstrated. In summary, data of this study suggest that Stx2a binds to AT, but does not induce major effects on plasmatic coagulation. In addition, no interaction with platelets occurred. The well-known non-beneficial administration of heparin in eHUS patients could be explained by the interaction of Stx2a with heparin.

Fibrinogen concentrate in dilutional coagulopathy: a dose study in pigs.

Dilutional coagulopathy can be reversed with fibrinogen concentrate. Effects of different fibrinogen dosages on clot function are not defined; high doses may increase the risk of thromboemboembolism. This study investigated the effect of six fibrinogen dosages on coagulation profile and blood loss in coagulopathic pigs. Forty-two pigs underwent a 60% hemodilution (HD) with hydroxyethylstarch (HES 130/0.4). After a standardized bone injury, animals randomly received 37.5, 75, 150, 300, 450 or 600 mg/kg fibrinogen (FGTW, LFB) or 500 ml of saline. Four hours later, a standardized liver injury was performed. Animals were then observed for two hours or until death. Blood loss was measured after death; Hemodynamic and coagulation parameters (thromboelastometry) were measured at baseline (BL), after HD, 15', 1, 2, 4 hours after fibrinogen administration and 2 hours after liver injury or right before the animals' death. Occurrence of thrombosis was examined in histological slides of internal organs. Statistical significance was set at p < 0.05. Doses of 150 mg/kg fibrinogen and higher reversed dilutional coagulopathy: Maximum clot firmness (MCF) was decreased after hemodilution (36 ± 3 mm vs. 65 ± 4 mm at BL, p < 0.05) and returned to BL after fibrinogen administration (69 ± 5 mm). Blood loss was significantly decreased with increased fibrinogen dosages: 42 ± 19 (sham), 34 ± 14 (75 mg/kg), 29 ± 13 (150 mg/kg), 28 ± 10 ml/kgbw (600 mg/kg). Fibrinogen (150-600 mg/kg) normalized clot firmness and decreased blood loss. No signs of hypercoagulability or thromboembolism were detected after high dosages.

Analysis of fibrin networks using topological data analysis - a feasibility study.

Blood clot formation, a crucial process in hemostasis and thrombosis, has garnered substantial attention for its implications in various medical conditions. Microscopic examination of blood clots provides vital insights into their composition and structure, aiding in the understanding of clot pathophysiology and the development of targeted therapeutic strategies. This study explores the use of topological data analysis (TDA) to assess plasma clot characteristics microscopically, focusing on the identification of the elements components, holes and Wasserstein distances. This approach should enable researchers to objectively classify fibrin networks based on their topologic architecture. We tested this mathematical characterization approach on plasma clots formed in static conditions from porcine and human citrated plasma samples, where the effect of dilution and direct thrombin inhibition was explored. Confocal microscopy images showing fluorescence labeled fibrin networks were analyzed. Both treatments resulted in visual differences in plasma clot architecture, which could be quantified using TDA. Significant differences between baseline and diluted samples, as well as blood anticoagulated with argatroban, were detected mathematically. Therefore, TDA could be indicative of clots with compromised stability, providing a valuable tool for thrombosis risk assessment. In conclusion, microscopic examination of plasma clots, coupled with Topological Data Analysis, offers a promising avenue for comprehensive characterization of clot microstructure. This method could contribute to a deeper understanding of clot pathophysiology and thereby refine our ability to assess clot characteristics.

Normothermic Machine Perfusion Reduces Transfusion Requirements Even After Static Cold Storage: A 1 y Retrospective Single-center Analysis.

Background: Normothermic machine perfusion (NMP) of liver grafts has been shown to reduce intraoperative catecholamine consumption and the need for allogenic blood products after reperfusion compared with organs undergoing classical static cold storage (SCS). This study aimed to investigate the effects of an NMP phase after SCS (NMP after SCS) of liver grafts in terms of postreperfusion hemodynamics and transfusion requirements. Methods: Eighteen recipients of NMP after SCS grafts were matched according to recipient age, donor age, and model for end-stage liver disease score in a 1:2 ratio with recipients of an SCS graft. Postreperfusion hemodynamics and the need for catecholamines, blood products, and clotting factors were compared. Results: After reperfusion of the organ, patients in the NMP after SCS group showed significantly reduced transfusion requirements for packed red blood cells and platelet concentrates compared with patients of the SCS group (P < 0.001 and P = 0.018, respectively). In addition, patients in the NMP after SCS group received less fibrinogen concentrate (NMP after SCS group 0 [0-1.5] g versus SCS group 2 [0-4] g; P = 0.0163). No differences in postreperfusion hemodynamics could be detected between groups. Conclusions: This retrospective analysis shows that NMP reduces postreperfusion requirements of red blood cells, platelet concentrates, and fibrinogen concentrate even if installed after a phase of organ SCS, because it may be practiced on most centers where NMP is available.

Individualised flow-controlled ventilation reduces applied mechanical power and improves ventilation efficiency in a porcine intra-abdominal hypertension model.

BACKGROUND: Aim of this study was to evaluate feasibility and effects of individualised flow-controlled ventilation (FCV), based on compliance guided pressure settings, compared to standard of pressure-controlled ventilation (PCV) in a porcine intra-abdominal hypertension (IAH) model. The primary aim of this study was to investigate oxygenation. Secondary aims were to assess respiratory and metabolic variables and lung tissue aeration. METHODS: Pigs were randomly assigned to FCV (n = 9) and PCV (n = 9). IAH was induced by insufflation of air into the abdomen to induce IAH grades ranging from 0 to 3. At each IAH grade FCV was undertaken using compliance guided pressure settings, or PCV (n = 9) was undertaken with the positive end-expiratory pressure titrated for maximum compliance and the peak pressure set to achieve a tidal volume of 7 ml/kg. Gas exchange, ventilator settings and derived formulas were recorded at two timepoints for each grade of IAH. Lung aeration was assessed by a computed tomography scan at IAH grade 3. RESULTS: All 18 pigs (median weight 54 kg [IQR 51-67]) completed the observation period of 4 h. Oxygenation was comparable at each IAH grade, but a significantly lower minute volume was required to secure normocapnia in FCV at all IAH grades (7.6 vs. 14.4, MD - 6.8 (95% CI - 8.5 to - 5.2) l/min; p < 0.001). There was also a significant reduction of applied mechanical power being most evident at IAH grade 3 (25.9 vs. 57.6, MD - 31.7 (95% CI - 39.7 to - 23.7) J/min; p < 0.001). Analysis of Hounsfield unit distribution of the computed tomography scans revealed a significant reduction in non- (5 vs. 8, MD - 3 (95% CI - 6 to 0) %; p = 0.032) and poorly-aerated lung tissue (7 vs. 15, MD - 6 (95% CI - 13 to - 3) %, p = 0.002) for FCV. Concomitantly, normally-aerated lung tissue was significantly increased (84 vs. 76, MD 8 (95% CI 2 to 15) %; p = 0.011). CONCLUSIONS: Individualised FCV showed similar oxygenation but required a significantly lower minute volume for CO2-removal, which led to a remarkable reduction of applied mechanical power. Additionally, there was a shift from non- and poorly-aerated lung tissue to normally-aerated lung tissue in FCV compared to PCV.

The effects of bolus compared to continuous administration of adrenaline on cerebral oxygenation during experimental cardiopulmonary resuscitation.

Background: Bolus administration of adrenaline during cardiopulmonary resuscitation (CPR) results in only short-term increases in systemic and cerebral perfusion pressure (CePP) with unclear effects on cerebral oxygenation. The aim of this study was to investigate the effects of bolus compared to continuous adrenaline administration on cerebral oxygenation in a porcine CPR model. Methods: After five minutes of cardiac arrest, mechanical CPR was performed for 15 min. Adrenaline (45 µg/kg) was administered either as a bolus every five minutes or continuously over the same period via an infusion pump. Main outcome parameter was brain tissue oxygen tension (PbtO2), secondary outcome parameters included mean arterial pressure (MAP), intracranial pressure (ICP), CePP and cerebral regional oxygen saturation (rSO2) as well as arterial and cerebral venous blood gases. Results: During CPR, mean MAP (45 ± 8 mmHg vs. 38 ± 8 mmHg; p = 0.0827), mean ICP (27 ± 7 mmHg vs. 20 ± 7 mmHg; p = 0.0653) and mean CePP (18 ± 8 mmHg vs. 18 ± 8 mmHg; p = 0.9008) were similar in the bolus and the continuous adrenaline group. Also, rSO2 (both 24 ± 6 mmHg; p = 0.9903) and cerebral venous oxygen saturation (18 ± 12% versus 27.5 ± 12%; p = 0.1596) did not differ. In contrast, relative PbtO2 reached higher values in the continuous group after five minutes of CPR and remained significantly higher than in the bolus group until the end of resuscitation. Conclusion: Continuous administration of adrenaline improved brain tissue oxygen tension compared with bolus administration during prolonged CPR.

Effects of fibrinogen concentrate after shock/resuscitation: a comparison between in vivo microvascular clot formation and thromboelastometry*.

OBJECTIVES: Dilutional coagulopathy after resuscitation with crystalloids/colloids clinically often appears as diffuse microvascular bleeding. Administration of fibrinogen reduces bleeding and increases maximum clot firmness, measured by thromboelastometry. Study objective was to implement a model where microvascular bleeding can be directly assessed by visualizing clot formation in microvessels, and correlations can be made to thromboelastometry. DESIGN: Randomized animal study. SETTING: University research laboratory. SUBJECTS: Male Syrian Golden hamsters. INTERVENTIONS: Microvessels of Syrian Golden hamsters fitted with a dorsal window chamber were studied using videomicroscopy. After 50% hemorrhage followed by 1 hour of hypovolemia resuscitation with 35% of blood volume using a high-molecular-weight hydroxyethyl starch solution (Hextend, Hospira, MW 670 kD) occurred. Animals were then treated with 250 mg/kg fibrinogen IV (Laboratoire français du Fractionnement et des Biotechnologies, Paris, France) or an equal volume of saline before venular vessel wall injuries was made by directed laser irradiation, and the ability of microthrombus formation was assessed. MEASUREMENTS AND MAIN RESULTS: Thromboelastometric measurements of maximum clot firmness were performed at the beginning and at the end of the experiment. Resuscitation with hydroxyethyl starch and sham treatment significantly decreased FIBTEM maximum clot firmness from 32 ± 9 mm at baseline versus 13 ± 5 mm after sham treatment (p < 0.001). Infusion of fibrinogen concentrate significantly increased maximum clot firmness, restoring baseline levels (baseline 32 ± 9 mm; after fibrinogen administration 29 ± 2 mm). In vivo microthrombus formation in laser-injured vessels significantly increased in fibrinogen-treated animals compared with sham (77% vs 18%). CONCLUSIONS: Fibrinogen treatment leads to increased clot firmness in dilutional coagulopathy as measured with thromboelastometry. At the microvascular level, this increased clot strength corresponds to an increased prevalence of thrombus formation in vessels injured by focused laser irradiation.

Hypertonic treatment of acute respiratory distress syndrome.

Many viral infections, including the COVID-19 infection, are associated with the hindrance of blood oxygenation due to the accumulation of fluid, inflammatory cells, and cell debris in the lung alveoli. This condition is similar to Acute Respiratory Distress Syndrome (ARDS). Mechanical positive-pressure ventilation is often used to treat this condition, even though it might collapse pulmonary capillaries, trapping red blood cells and lowering the lung's functional capillary density. We posit that the hyperosmotic-hyperoncotic infusion should be explored as a supportive treatment for ARDS. As a first step in verifying the feasibility of this ARDS treatment, we model the dynamics of alveolar fluid extraction by osmotic effects. These are induced by increasing blood plasma osmotic pressure in response to the increase of blood NaCl concentration. Our analysis of fluid drainage from a plasma-filled pulmonary alveolus, in response to the intravenous infusion of 100 ml of 1.28 molar NaCl solution, shows that alveoli empty of fluid in approximately 15 min. These modeling results are in accordance with available experimental and clinical data; no new data were collected. They are used to calculate the temporal change of blood oxygenation, as oxygen diffusion hindrance decreases upon absorption of the alveolar fluid into the pulmonary circulation. Our study suggests the extraordinary speed with which beneficial effects of the proposed ARDS treatment are obtained and highlight its practicality, cost-efficiency, and avoidance of side effects of mechanical origin.

[Anesthesia for organ transplant patients]. / Anästhesie bei organtransplantierten Patient:innen.

Organ transplant patients who must undergo nontransplant surgical interventions can be challenging for the anesthesiologists in charge. On the one hand, it is important to carefully monitor the graft function in the perioperative period with respect to the occurrence of a possible rejection reaction. On the other hand, the ongoing immunosuppression may have to be adapted to the perioperative requirements in terms of the active substance and the route of administration, the resulting increased risk of infection and possible side effects (e.g., myelosuppression, nephrotoxicity and impairment of wound healing) must be included in the perioperative treatment concept. Furthermore, possible persistent comorbidities of the underlying disease and physiological peculiarities as a result of the organ transplantation must be taken into account. Support can be obtained from the expertise of the respective transplantation center.

Flow-controlled versus pressure-controlled ventilation in cardiac surgery with cardiopulmonary bypass - A single-center, prospective, randomized, controlled trial.

STUDY OBJECTIVE: Multifactorial comparison of flow-controlled ventilation (FCV) to standard of pressure-controlled ventilation (PCV) in terms of oxygenation in cardiac surgery patients after chest closure. DESIGN: Prospective, non-blinded, randomized, controlled trial. SETTING: Operating theatre at an university hospital, Austria. PATIENTS: Patients scheduled for elective, open, on-pump, cardiac surgery. INTERVENTIONS: Participants were randomized to either individualized FCV (compliance guided end-expiratory and peak pressure setting) or control of PCV (compliance guided end-expiratory pressure setting and tidal volume of 6-8 ml/kg) for the duration of surgery. MEASUREMENTS: The primary outcome measure was oxygenation (PaO2/FiO2) 15 min after intraoperative chest closure. Secondary endpoints included CO2-removal assessed as required minute volume to achieve normocapnia and lung tissue aeration assessed by Hounsfield unit distribution in postoperative computed tomography scans. MAIN RESULTS: Between April 2020 and April 2021 56 patients were enrolled and 50 included in the primary analysis (mean age 70 years, 38 (76%) men). Oxygenation, assessed by PaO2/FiO2, was significantly higher in the FCV group (n = 24) compared to the control group (PCV, n = 26) (356 vs. 309, median difference (MD) 46 (95% CI 3 to 90) mmHg; p = 0.038). Additionally, the minute volume required to obtain normocapnia was significantly lower in the FCV group (4.0 vs. 6.1, MD -2.0 (95% CI -2.5 to -1.5) l/min; p < 0.001) and correlated with a significantly lower exposure to mechanical power (5.1 vs. 9.8, MD -5.1 (95% CI -6.2 to -4.0) J/min; p < 0.001). Evaluation of lung tissue aeration revealed a significantly reduced amount of non-aerated lung tissue in FCV compared to PCV (5 vs. 7, MD -3 (95% CI -4 to -1) %; p < 0.001). CONCLUSIONS: In patients undergoing on-pump, cardiac surgery individualized FCV significantly improved oxygenation and lung tissue aeration compared to PCV. In addition, carbon dioxide removal was accomplished at a lower minute volume leading to reduced applied mechanical power.