Membrane oxygenator longevity was higher in argatroban-treated patients undergoing vvECMO.

BACKGROUND: In severe acute respiratory distress syndrome (ARDS), venovenous extracorporeal membrane oxygenation (vvECMO) can be a lifesaver. However, anticoagulation therapy is mandatory because the nonendothelial extracorporeal surface increases the risk of thromboembolic problems. Heparin is still the most common anticoagulant, but argatroban could be an alternative. This work investigates whether argatroban offers a therapeutic advantage over heparin during vvECMO. METHODS: We performed a retrospective cohort study of patients who underwent vvECMO for severe ARDS and received heparin or argatroban as anticoagulation therapy. Demographic variables, intensive care unit (ICU) treatment and outcome parameters were evaluated. The primary outcome parameter was the operating time of the membrane oxygenator normalized to the duration of vvECMO treatment. Secondary outcome parameters were transfusion requirements normalized to the duration of vvECMO therapy. RESULTS: Fifty seven patients from January 2019 to February 2021 underwent vvECMO and were included in this study. Thirty three patients received heparin and 24 patients argatroban as anticoagulatory therapy. The groups did not differ in demographics, ICU scoring systems, or comorbidities. Platelet counts and partial prothrombin time did not differ between the two groups during the first 6 days of vvECMO. The argatroban group had lower requirements for red blood cells, platelets and fresh frozen plasma. The mean runtime of the individual membrane oxygenator increased from 12.3 days (heparin group) to 16.6 days in the argatroban group. CONCLUSIONS: Our findings suggest that argatroban can be considered as anticoagulant during vvECMO.

Early vvECMO implantation may be associated with lower mortality in ARDS.

BACKGROUND: Venovenous extracorporeal membrane oxygenation (vvECMO) is used to treat hypoxia in patients with severe acute respiratory distress syndrome (ARDS). Nevertheless, uncertainty exists regarding the optimal timing of initiation of vvECMO therapy. We aimed to investigate the association between number of days of invasive mechanical ventilation (IMV) prior to vvECMO implantation and mortality. METHODS: In this retrospective observational study, we included patients treated at an academic intensive care unit with vvECMO for severe ARDS. The primary outcome was all-cause 28-day mortality. We conducted a multivariate logistic regression analysis to estimate the association between number of days of IMV prior to vvECMO implantation and mortality after adjustment for confounders. RESULTS: Out of 274 patients who underwent ECMO for severe ARDS, 158 patients (median age: 58 years) with relevant data were included in the analysis. The mean duration of IMV prior to vvECMO was significantly shorter in survivors than in nonsurvivors [survivors median: 1; interquartile range: 1-3; non-survivors median 4; interquartile range: 1-5.75; p = 0.0001). Logistic regression showed an association between the duration of ventilation prior to vvECMO and patient mortality. The odds ratio for the all-cause 28-day mortality and in-hospital mortality was significantly reduced in patients who received vvECMO within the first 5 days of IMV. CONCLUSIONS: Early vvECMO implantation may be associated with lower mortality in ARDS.

Inhaled prostacyclin therapy in the acute respiratory distress syndrome: a randomized controlled multicenter trial.

BACKGROUND: Acute respiratory distress syndrome (ARDS) results in significant hypoxia, and ARDS is the central pathology of COVID-19. Inhaled prostacyclin has been proposed as a therapy for ARDS, but data regarding its role in this syndrome are unavailable. Therefore, we investigated whether inhaled prostacyclin would affect the oxygenation and survival of patients suffering from ARDS. METHODS: We performed a prospective randomized controlled single-blind multicenter trial across Germany. The trial was conducted from March 2019 with final follow-up on 12th of August 2021. Patients with moderate to severe ARDS were included and randomized to receive either inhaled prostacyclin (3 times/day for 5 days) or sodium chloride (Placebo). The primary outcome was the oxygenation index in the intervention and control groups on Day 5 of therapy. Secondary outcomes were mortality, secondary organ failure, disease severity and adverse events. RESULTS: Of 707 patients approached 150 patients were randomized to receive inhaled prostacyclin (n = 73) or sodium chloride (n = 77). Data from 144 patients were analyzed. The baseline PaO2/FiO2 ratio did not differ between groups. The primary analysis of the study was negative, and prostacyclin improved oxygenation by 20 mmHg more than Placebo (p = 0.17). Secondary analysis showed that the oxygenation was significantly improved in patients with ARDS who were COVID-19-positive (34 mmHg, p = 0.04). Mortality did not differ between groups. Secondary organ failure and adverse events were similar in the intervention and control groups. CONCLUSIONS: The primary result of our study was negative. Our data suggest that inhaled prostacyclin might be beneficial treatment in patients with COVID-19 induced ARDS. TRIAL REGISTRATION: The study was approved by the Institutional Review Board of the Research Ethics Committee of the University of Tübingen (899/2018AMG1) and the corresponding ethical review boards of all participating centers. The trial was also approved by the Federal Institute for Drugs and Medical Devices (BfArM, EudraCT No. 2016003168-37) and registered at clinicaltrials.gov (NCT03111212) on April 6th 2017.

Machine learning identifies ICU outcome predictors in a multicenter COVID-19 cohort.

BACKGROUND: Intensive Care Resources are heavily utilized during the COVID-19 pandemic. However, risk stratification and prediction of SARS-CoV-2 patient clinical outcomes upon ICU admission remain inadequate. This study aimed to develop a machine learning model, based on retrospective & prospective clinical data, to stratify patient risk and predict ICU survival and outcomes. METHODS: A Germany-wide electronic registry was established to pseudonymously collect admission, therapeutic and discharge information of SARS-CoV-2 ICU patients retrospectively and prospectively. Machine learning approaches were evaluated for the accuracy and interpretability of predictions. The Explainable Boosting Machine approach was selected as the most suitable method. Individual, non-linear shape functions for predictive parameters and parameter interactions are reported. RESULTS: 1039 patients were included in the Explainable Boosting Machine model, 596 patients retrospectively collected, and 443 patients prospectively collected. The model for prediction of general ICU outcome was shown to be more reliable to predict "survival". Age, inflammatory and thrombotic activity, and severity of ARDS at ICU admission were shown to be predictive of ICU survival. Patients' age, pulmonary dysfunction and transfer from an external institution were predictors for ECMO therapy. The interaction of patient age with D-dimer levels on admission and creatinine levels with SOFA score without GCS were predictors for renal replacement therapy. CONCLUSIONS: Using Explainable Boosting Machine analysis, we confirmed and weighed previously reported and identified novel predictors for outcome in critically ill COVID-19 patients. Using this strategy, predictive modeling of COVID-19 ICU patient outcomes can be performed overcoming the limitations of linear regression models. Trial registration "ClinicalTrials" (clinicaltrials.gov) under NCT04455451.

A case report of fatal disseminated fungal sepsis in a patient with ARDS and extracorporeal membrane oxygenation.

BACKGROUND: With the following report we want to present an unusual case of a patient suffering from acute respiratory distress syndrome with early discovery of bacterial pathogens in bronchoalveolar liquid samples that developed a fatal undiscovered disseminated fungal infection. CASE PRESENTATION: A 67-year-old man was admitted to our university hospital with dyspnea. Progressive respiratory failure developed leading to admission to the intensive care unit, intubation and prone positioning was necessary. To ensure adequate oxygenation and lung protective ventilation veno-venous extracorporeal membrane oxygenation was established. Despite maximal therapy and adequate antiinfective therapy of all discovered pathogens the condition of the patient declined further and he deceased. Postmortem autopsy revealed Mucor and Aspergillus mycelium in multiple organs such as lung, heart and pancreas as the underlying cause of his deterioration and death. CONCLUSION: Routine screening re-evaluation of every infection is essential for adequate initiation and discontinuation of every antiinfective therapy. In cases with unexplained deterioration and unsuccessful sampling the possibility for diagnostic biopsies should be considered.

[Do we Isolate Patients or Bugs? Challenging Isolation Precautions]. / Isolieren wir Keime oder Patienten? Isolationsmaßnahmen unter der Lupe.

Isolation of patients with multidrug-resistant organisms (MRGN) has been recommended since years. Recent evidence suggests no benefit by this isolation procedure. Furthermore, isolation precautions may have potential negative effects on patient well-being and may increase therapeutic error.Rather than blocking patients up in a room, implementing and continuous education about standard precautions as hand washing and contact awareness may decrease spread of MRGN and other resistant bacteria. In this context, evidence about mechanism of resistance transfer between bacteria is still expanding. Education about these mechanisms inside and outside the body may help to corroborate the appreciation about implementation of standard precautions. In addition, the awareness of antibiotic stewardship in this context has to be underlined. Prevention of spreading bacteria is not done by isolation in room. In fact, it is a multifactorial continuous cycle of planning, teaching, surveillance and transfer of knowledge. Combination of education, compliance to standard precautions and continuous education may be a big step forward in fighting MRGN transmission and progression.

Safety of transesophageal echocardiography during extracorporeal life support.

INTRODUCTION:: Use of extracorporeal life support (ECLS) has significantly increased in critically ill patients refractory to medical management. ECLS requires systemic anticoagulation to avoid thromboembolic complications and superimposed coagulopathies are common. Transesophageal echocardiography (TEE) is frequently employed to assess cannula position and cardiac function during extracorporeal therapy. The goal of this study was to assess whether TEE probe insertion and removal in systemically anticoagulated ECLS patients was safe compared to patients without ECLS and normal coagulation studies. METHODS:: Eighty-seven separate TEE examinations in 53 adult ECLS patients were analyzed. Detailed complication profiles were logged for each patient from initiation through discontinuation of ECLS. Routine coagulation testing was recorded within two hours prior to the TEE exams. Controls consisted of age- and gender-matched patients undergoing perioperative TEE without ECLS and normal coagulation (N=87). RESULTS:: Overall TEE-associated morbidity in ECLS patients was 2.3% and consisted of minor oropharyngeal bleeding (2/87 TEE exams) exclusively. The patients presenting with oropharyngeal bleeding received heparin for anticoagulation and had two or more abnormal coagulation studies at the time of TEE. Seventy-nine percent of ECLS patients received intravenous heparin infusions, 6.8% argatroban and 3.4% epoprostenol. Ten-point-eight percent of patients were not anticoagulated at the time of TEE because of pre-existing bleeding complications and/or deranged plasmatic coagulation profiles. No major complications (e.g., esophageal perforation, gastrointestinal bleeding, accidental extubation) were recorded in either group. CONCLUSIONS:: TEE remained safe in critically ill patients under ECLS, despite systemic anticoagulation, during probe insertion, manipulation and removal. TEE-related complications pertained solely to oropharyngeal bleeding amenable to conservative management.

Explainable Boosting Machine approach identifies risk factors for acute renal failure.

BACKGROUND: Risk stratification and outcome prediction are crucial for intensive care resource planning. In addressing the large data sets of intensive care unit (ICU) patients, we employed the Explainable Boosting Machine (EBM), a novel machine learning model, to identify determinants of acute kidney injury (AKI) in these patients. AKI significantly impacts outcomes in the critically ill. METHODS: An analysis of 3572 ICU patients was conducted. Variables such as average central venous pressure (CVP), mean arterial pressure (MAP), age, gender, and comorbidities were examined. This analysis combined traditional statistical methods with the EBM to gain a detailed understanding of AKI risk factors. RESULTS: Our analysis revealed chronic kidney disease, heart failure, arrhythmias, liver disease, and anemia as significant comorbidities influencing AKI risk, with liver disease and anemia being particularly impactful. Surgical factors were also key; lower GI surgery heightened AKI risk, while neurosurgery was associated with a reduced risk. EBM identified four crucial variables affecting AKI prediction: anemia, liver disease, and average CVP increased AKI risk, whereas neurosurgery decreased it. Age was a progressive risk factor, with risk escalating after the age of 50 years. Hemodynamic instability, marked by a MAP below 65 mmHg, was strongly linked to AKI, showcasing a threshold effect at 60 mmHg. Intriguingly, average CVP was a significant predictor, with a critical threshold at 10.7 mmHg. CONCLUSION: Using an Explainable Boosting Machine enhance the precision in AKI risk factors in ICU patients, providing a more nuanced understanding of known AKI risks. This approach allows for refined predictive modeling of AKI, effectively overcoming the limitations of traditional statistical models.

Semaphorin 7A coordinates neutrophil response during pulmonary inflammation and sepsis.

ABSTRACT: Pulmonary defense mechanisms are critical for host integrity during pneumonia and sepsis. This defense is fundamentally dependent on the activation of neutrophils during the innate immune response. Recent work has shown that semaphorin 7A (Sema7A) holds significant impact on platelet function, yet its role on neutrophil function within the lung is not well understood. This study aimed to identify the role of Sema7A during pulmonary inflammation and sepsis. In patients with acute respiratory distress syndrome (ARDS), we were able to show a correlation between Sema7A and oxygenation levels. During subsequent workup, we found that Sema7A binds to the neutrophil PlexinC1 receptor, increasing integrins, and L-selectin on neutrophils. Sema7A prompted neutrophil chemotaxis in vitro and the formation of platelet-neutrophil complexes in vivo. We also observed altered adhesion and transmigration of neutrophils in Sema7A-/-animals in the lung during pulmonary inflammation. This effect resulted in increased number of neutrophils in the interstitial space of Sema7A-/- animals but reduced numbers of neutrophils in the alveolar space during pulmonary sepsis. This finding was associated with significantly worse outcome of Sema7A-/- animals in a model of pulmonary sepsis. Sema7A has an immunomodulatory effect in the lung, affecting pulmonary sepsis and ARDS. This effect influences the response of neutrophils to external aggression and might influence patient outcome. This trial was registered at www.ClinicalTrials.gov as #NCT02692118.

Patient-Related Factors Associated with Adverse Outcomes Following Weaning from Veno-Arterial Extracorporeal Membrane Oxygenation.

BACKGROUND: Veno-arterial extracorporeal membrane oxygenation (vaECMO) removal reflects a critical moment and factors of adverse outcomes are incompletely understood. Thus, we studied various patient-related factors during vaECMO removal to determine their association with outcomes. METHODS: A total of 58 patients from a university hospital were included retrospectively. Demographic, clinical, and echocardiographic parameters were recorded while under vaECMO support, as well as the need for inotropic and vasoactive-inotropic scores (VIS). Successful weaning was defined as 28-day survival without reinitiation of vaECMO. RESULTS: Patient age differed significantly between patients with a successful and a failed vaECMO weaning (54 ± 14 vs. 62 ± 12 years, p = 0.029). In univariable logistic regression, age (OR 0.952 (0.909-0.997), p = 0.038), the necessities for inotropic agents at the time of echocardiography (OR 0.333 (0.113-0.981), p = 0.046), and vaECMO removal (OR 0.266 (0.081-0.877), p = 0.030) as well as the dobutamine dose during removal (OR 0.649 (0.473-0.890), p = 0.007), were significantly associated with a successful weaning from vaECMO. Age (HR 1.048 (1.006-1.091), p = 0.024) and the VIS (HR 1.030 (1.004-1.056), p = 0.025) at the time of vaECMO removal were independently associated with survival in bivariable Cox regression. In Kaplan-Meier analysis, a VIS of >5.1 at vaECMO removal was associated with impaired survival (log-rank p = 0.025). CONCLUSIONS: In this cohort, age and the extent of vasoactive-inotropic agents were associated with adverse outcomes following vaECMO, whereas echocardiographic biventricular function during vaECMO support was not.

Daptomycin Pharmacokinetics in Blood and Wound Fluid in Critical Ill Patients with Left Ventricle Assist Devices.

Daptomycin is a cyclic lipopeptide antibiotic with bactericidal effects against multidrug-resistant Gram-positive bacteria, including methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococcus faecalis (VRE). For critically ill patients, especially in the presence of implants, daptomycin is an important therapeutic option. Left ventricle assist devices (LVADs) can be utilized for intensive care patients with end-stage heart failure as a bridge to transplant. We conducted a single-center prospective trial with critically ill adults with LVAD who received prophylactic anti-infective therapy with daptomycin. Our study aimed to evaluate the pharmacokinetics of daptomycin in the blood serum and wound fluids after LVAD implantation. Daptomycin concentration were assessed over three days using high-performance liquid chromatography (HPLC). We detected a high correlation between blood serum and wound fluid daptomycin concentration at 12 h (IC95%: 0.64 to 0.95; r = 0.86; p < 0.001) and 24 h (IC95%: -0.38 to 0.92; r = 0.76; p < 0.001) after antibiotic administration. Our pilot clinical study provides new insights into the pharmacokinetics of daptomycin from the blood into wound fluids of critically ill patients with LVADs.

Effects of different leukocyte subpopulations and flow conditions on leukocyte accumulation during reperfusion.

BACKGROUND/AIMS: The study examined the interdependent effects of shear stress and different leukocyte subpopulations on endothelial cell activation and cell interactions during low flow and reperfusion. METHODS: Human umbilical venous endothelial cells were perfused with either neutrophils or monocytes at different shear stress (2-0.25 dyn/cm(2)) and adhesion was quantified by microscopy. Effects of adherent neutrophils and monocytes on endothelial cell adhesion molecule expression were analyzed by flow cytometry after 4-hour static coincubation. After coincubation, the cocultures were reperfused with labeled neutrophils at 2 dyn/cm(2) and their adhesion was quantified selectively. For the control, endothelium monocultures with and without lipopolysaccharide activation were used. RESULTS: At 2 dyn/cm(2), adhesion did not exceed baseline levels on nonactivated endothelium. Decreasing shear stress to 0.25 dyn/cm(2) largely increased the adhesion of both leukocyte subpopulations, similar to the effect of lipopolysaccharide at 2 dyn/cm(2). However, only adherent monocytes increased adhesion molecule expression, whereas neutrophils had no effect. As a functional consequence, adherent monocytes largely increased neutrophil adhesion during reperfusion, whereas adherent neutrophils did not. CONCLUSION: Compromised shear stress is an autonomous trigger of leukocyte adhesion even in the absence of additional activators. Exceeding this immediate effect, adherent monocytes induce further endothelial activation and enhance further neutrophil adhesion during reperfusion.

Corrigendum: Methylene blue dosing strategies in critically ill adults with shock-A retrospective cohort study.

[This corrects the article DOI: 10.3389/fmed.2022.1014276.].

Methylene blue dosing strategies in critically ill adults with shock-A retrospective cohort study.

Background: Shock increases mortality in the critically ill and the mainstay of therapy is the administration of vasopressor agents to achieve hemodynamic targets. In the past, studies have found that the NO-pathway antagonist methylene blue improves hemodynamics. However, the optimal dosing strategy remains elusive. Therefore, we investigated the hemodynamic and ICU outcome parameters of three different dosing strategies for methylene blue. Methods: We performed a retrospective cohort study of patients in shock treated with methylene blue. Shock was defined as norepinephrine dose >0.1 µg/kg/min and serum lactate level >2 mmol/l at the start of methylene blue administration. Different demographic variables, ICU treatment, and outcome parameters were evaluated. To compare the differences in the administration of vasopressors or inotropes, the vasoactive inotropic score (VIS) was calculated at different time points after starting the administration of methylene blue. Response to methylene blue or mortality at 28 days were assessed. Results: 262 patients from July 2014 to October 2019 received methylene blue. 209 patients met the inclusion criteria. Three different dosing strategies were identified: bolus injection followed by continuous infusion (n = 111), bolus injection only (no continuous infusion; n = 59) or continuous infusion only (no bolus prior; n = 39). The groups did not differ in demographics, ICU scoring system, or comorbidities. In all groups, VIS decreased over time, indicating improved hemodynamics. Cardiogenic shock and higher doses of norepinephrine increased the chance of responding to methylene blue, while bolus only decreased the chance of responding to methylene blue treatment. 28-day mortality increased with higher SAPSII scores and higher serum lactate levels, while bolus injection followed by continuous infusion decreased 28-day mortality. No severe side effects were noted. Conclusion: In this cohort, methylene blue as a bolus injection followed by continuous infusion was associated with a reduced 28-day mortality in patients with shock. Prospective studies are needed to systematically evaluate the role of methylene blue in the treatment of shock.

Mechanisms of leukocyte distribution during sepsis: an experimental study on the interdependence of cell activation, shear stress and endothelial injury.

INTRODUCTION: This study was carried out to determine whether interactions of cell activation, shear stress and platelets at sites of endothelial injury explain the paradoxical maldistribution of activated leukocytes during sepsis away from local sites of infection towards disseminated leukocyte accumulation at remote sites. METHODS: Human umbilical venous endothelial cells (HUVEC) and polymorphonuclear neutrophils (PMN) were activated with lipopolysaccharide at 100 and 10 ng/ml to achieve adhesion molecule patterns as have been reported from the hyper- and hypo-inflammatory stage of sepsis. To examine effects of leukocyte activation on leukocyte-endothelial interactions, activated HUVEC were perfused with activated and non-activated neutrophils in a parallel plate flow chamber. Adhesion molecule expression and function were assessed by flow cytometry and blocking antibodies. In a subset of experiments the sub-endothelial matrix was exposed and covered with platelets to account for the effects of endothelial injury. To investigate interactions of these effects with flow, all experiments were done at various shear stress levels (3 to 0.25 dyne/cm(2)). Leukocyte-endothelial interactions were analyzed by videomicroscopy and analysis of covariance. RESULTS: Activation of neutrophils rendered adhesion increasingly dependent on shear stress reduction. At normal shear stress, shedding of L-selectin decreased adhesion by 56%. Increased rolling fractions of activated PMN at low shear stress revealed impaired integrin affinity despite numerical up-regulation of CD11b. On sub-maximally activated, intact HUVEC shear stress became the prevailing determinant of adhesion. Presence of a platelet-covered injury with high surface density of P-selectin was the strongest variable for adhesion. When compared to maximally activated HUVEC, platelets increased neutrophil adhesion by 2.7-fold. At sub-maximal activation a 10-fold increase was observed (P < 0.05 for all). CONCLUSIONS: L-selectin shedding and integrin dysfunction render leukocyte adhesion increasingly susceptible to shear stress and alternative adhesion receptors. In combination, these effects inhibit recruitment to normally perfused sites with intact endothelium and favor maldistribution towards sites with compromised perfusion or endothelial injury.

Early Driving Pressure Changes Predict Outcomes during Venovenous Extracorporeal Membrane Oxygenation for Acute Respiratory Distress Syndrome.

BACKGROUND: Extracorporeal membrane oxygenation (ECMO) serves as a rescue therapy when systemic hypoxia persists despite conventional care for severe acute respiratory distress syndrome (ARDS). Due to the extracorporeal gas exchange, the p aO2/F iO2 ratio cannot be used as the primary marker for disease severity and progression. Therefore, we performed a propensity score-matched analysis to identify other potential predictors of outcomes in patients supported by ECMO therapy. RESULTS: Between December 2014 and May 2018, 105 patients underwent venovenous ECMO in our institution. From these patients, we identified 28 who died during ECMO therapy and assigned 28 control patients using propensity score matching based on the following criteria: age, ARDS severity, and SAPSII score at admission. A statistical evaluation of the patient characteristics, intensive care data, morbidities, respiratory system variables, and outcomes was performed. The baseline patient characteristics did not differ between groups and ECMO was placed on day 1 in all patients. The analyzed variables of respiratory mechanics, such as the plateau pressure, positive end-expiratory pressure, and tidal volume, did not differ between groups. The driving pressure before ECMO was equal between the nonsurvivors and the controls. Twelve hours after initiation of ECMO therapy, the driving pressure decreased by 40.8% in the survivors but by only 20.1% in the nonsurvivors. CONCLUSIONS: We report that very early driving pressure changes can serve as an indicator of disease severity and predict patient survival following ECMO therapy.

Intravenous immunoglobulin fails to improve ARDS in patients undergoing ECMO therapy.

BACKGROUND: Acute respiratory distress syndrome (ARDS) is associated with high mortality rates. ARDS patients suffer from severe hypoxemia, and extracorporeal membrane oxygenation (ECMO) therapy may be necessary to ensure oxygenation. ARDS has various etiologies, including trauma, ischemia-reperfusion injury or infections of various origins, and the associated immunological responses may vary. To support the immunological response in this patient collective, we used intravenous IgM immunoglobulin therapy to enhance the likelihood of pulmonary recovery. METHODS: ARDS patients admitted to the intensive care unit (ICU) who were placed on ECMO and treated with (IVIG group; n = 29) or without (control group; n = 28) intravenous IgM-enriched immunoglobulins for 3 days in the initial stages of ARDS were analyzed retrospectively. RESULTS: The baseline characteristics did not differ between the groups, although the IVIG group showed a significantly reduced oxygenation index compared to the control group. We found no differences in the length of ICU stay or ventilation parameters. We did not find a significant difference between the groups for the extent of inflammation or for overall survival. CONCLUSION: We conclude that administration of IgM-enriched immunoglobulins as an additional therapy did not have a beneficial effect in patients with severe ARDS requiring ECMO support. TRIAL REGISTRATION: Clinical Trials: NCT02961166; retrospectively registered.

Effect of synthetic colloids on major histocompatibility complex class II expression.

STUDY OBJECTIVE: Synthetic colloids are used for perioperative fluid management. We hypothesized that their use may be associated with changes in major histocompatibility complex (MHC) class II expression. This could affect patients' morbidity and mortality during clinical intervention. SETTING: University research laboratory. SUBJECTS: Whole blood samples from healthy volunteers. INTERVENTIONS: Whole blood samples from healthy volunteers (n = 6) were incubated with different concentrations of hydroxyethyl starch (HES) from maize and potato (pHES), dextran, and polygelin (gelatine) for 24 hours with or without 100 U/mL human interferon gamma (IFN-gamma; stimulus for MHC class II expression). The expression of human leukocyte antigen (HLA): HLA-DR, HLA-DQ, and HLA-DP was detected simultaneously by a fluoresceinisothiocyanate (FITC)-labeled antibody and analyzed by flow cytometry on lymphocytes and monocytes. MEASUREMENTS AND MAIN RESULTS: Hydroxyethyl starch, pHES, and dextran induced a significant increase in HLA expression. The induction of MHC class II was independent of the structure (50 mg/mL: control, 8.7+/-1.4%; HES, 28 +/- 9.7%; pHES, 29.8 +/- 11.7%; and dextran, 50.2 +/- 8.1%). In contrast, polygelin increased HLA expression only at the highest concentration of gelatine (5 mg/mL, 7.8 +/- 1%; 50 mg/mL, 7.6 +/- 0.8%; 100 mg/mL, 7.3 +/- 1%; 200 mg/mL,16.2 +/- 2.3%). The addition of IFN-gamma decreased HLA expression in presence of highest concentration of HES and dextran. CONCLUSION: In an ex vivo laboratory setting, we demonstrate that high concentrations of plasma expanders are associated with increased HLA expression on lymphocytes and monocytes. However, further in vivo studies are necessary to demonstrate the clinical significance of this observation.

Role of cross-allergies to latex in clinical routine of anesthesia.

STUDY OBJECTIVE: To determine the applicability and reliability of a screening questionnaire to detect patients at high-risk of latex allergy; to assess the importance of other allergies such as profilin allergies (pollinosis) for presence of latex sensitization; and to determine the clinical effectiveness of preemptive avoidance of latex exposure in high-risk patients. DESIGN: Prospective, clinical trial. SETTING: Operative theater of a university hospital. PATIENTS: 95 adult patients. INTERVENTIONS: Patients were preoperatively screened and classified for present latex allergy (high-risk and low-risk group) according to a specially designed screening questionnaire. Anesthesia and surgery in the high-risk group were performed strictly avoiding latex-containing materials. The low-risk group (other allergies including pollinosis) received routine treatment, without latex-avoidance. Effects of latex avoidance or exposure were evaluated by measuring specific IgE titers perioperatively. MEASUREMENTS AND MAIN RESULTS: According to the questionnaire, 45 patients at high risk were defined. Validity of classification of high-risk patients is supported by significantly higher total IgE and latex and grass profilin specific IgE compared to the low-risk group. There were no significant differences in other profilin-specific IgEs. In one case of severe anaphylactic reaction a drop of latex-specific IgE during surgery could be observed. CONCLUSION: The questionnaire allowed the identification of most patients at high risk for latex allergy. In isolated pollinosis no changes in any specific IgE levels were detectable. Strict avoidance of perioperative latex exposure in high-risk patients increases safety during anesthesia and surgery.