Extra Corporeal Membrane Oxygenation (ECMO) has become an accepted treatment option for severely ill patients. Due to a limited availability of ECMO support therapy, patients must often be transported to a specialised centre before or after cannulation. According to the ELSO guidelines, an ECMO specialist should be present for such interventions. Here we describe the safety and efficacy of a reduced team approach involving one anaesthesiologist, experienced in specialised intensive care medicine, and a specialised critical care nurse. This study is a 10 years retrospective, single institution analysis of all data collected between January 2007 and December 2016 from the medical records at the University Hospital Bonn, Germany. The Bonner mobile ECMO team was deployed in 170 cases for on-site evaluation for ECMO support therapy. 4 (2.4%) patients died prior to arrival or during the implementation of ECMO support. Of the remaining 166 patients, 126 were cannulated at the referring site, 40 were transported without ECMO. Of those, 21 were subsequently cannulated out our centre. 19 patients never received ECMO treatment. The primary indication for ECMO treatment was ARDS (159/166 patients). Veno-venous ECMO was initiated in 137, whilst 10 patients received veno-arterial ECMO treatment. Mean transportation time was 75 ± 36 min, and mean transport distance was 56 ± 57 km. In total, 26 complications were observed, three being directly transport-related. The overall survival was 55%. Initiation of extracorporeal membrane oxygenation and subsequent transport can be safely and efficiently performed by a two-man team with good outcome.

(1) Background: With the rise of multi-/pan-drug resistant (MDR/PDR) pathogens, the less utilized antibiotic Colistin has made a comeback. Colistin fell out of favor due to its small therapeutic range and high potential for toxicity. Today, it is used again as a last resort substance in treating MDR/PDR pathogens. Although new guidelines with detailed recommendations for Colistin dosing are available, finding the right dose in critically ill patients with renal failure remains difficult. Here, we evaluate the efficiency of the current guidelines’ recommendations by using high resolution therapeutic drug monitoring of Colistin. (2) Methods: We analyzed plasma levels of Colistin and its prodrug colisthimethate sodium (CMS) in 779 samples, drawn from eight PDR-infected ICU patients, using a HPLC-MS/MS approach. The impact of renal function on proper Colistin target levels was assessed. (3) Results: CMS levels did not correlate with Colistin levels. Over-/Underdosing occurred regardless of renal function and mode of renal replacement therapy. Colistin elimination half-time appeared to be longer than previously reported. (4) Conclusion: Following dose recommendations from the most current guidelines does not necessarily lead to adequate Colistin plasma levels. Use of Colistin without therapeutic drug monitoring might be unsafe and guideline adherence does not warrant efficient target levels in critically ill patients.

Sepsis is associated with a strong inflammatory reaction triggering a complex and prolonged immune response. Septic patients have been shown to develop sustained immunosuppression due to a reduced responsiveness of leukocytes to pathogens. Changes in cellular metabolism of leukocytes have been linked to this phenomenon and contribute to the ongoing immunological derangement. However, the underlying mechanisms of these phenomena are incompletely understood. In cell culture models, we mimicked LPS tolerance conditions to provide evidence that epigenetic modifications account for monocyte metabolic changes which cause immune paralysis in restimulated septic monocytes. In detail, we observed differential methylation of CpG sites related to metabolic activity in human PBMCs 18 h after septic challenge. The examination of changes in immune function and metabolic pathways was performed in LPS-tolerized monocytic THP-1 cells. Passaged THP-1 cells, inheriting initial LPS challenge, presented with dysregulation of cytokine expression and oxygen consumption for up to 7 days after the initial LPS treatment. Proinflammatory cytokine concentrations of TNFα and IL1β were significantly suppressed following a second LPS challenge (p<0.001) on day 7 after first LPS stimulation. However, the analysis of cellular metabolism did not reveal any noteworthy alterations between tolerant and nontolerant THP-1 monocytes. No quantitative differences in ATP and NADH synthesis or participating enzymes of energy metabolism occurred. Our data demonstrate that the function and epigenetic modifications of septic and tolerized monocytes can be examined in vitro with the help of our LPS model. Changes in CpG site methylation and monocyte function point to a correlation between epigenetic modification in metabolic pathways and reduced monocyte function under postseptic conditions.

Breakdown of the alveolo-capillary wall is pathognomonic for Acute Lung Injury (ALI). Angiopoietins, vascular-specific growth factors, are linked to endothelial barrier dysfunction, and elevated Angiopoietin-2 (ANG2) levels are associated with poor outcome of ALI patients. Specialized immune cells, referred to as ‘TIE2-expressing monocytes and macrophages’ (TEM), were shown to specifically respond to ANG2 binding. However, their involvement in acute inflammatory processes is so far completely undescribed. Thus, our aim was to assess the dynamics of TEMs in a murine model of ALI. Intratracheal instillation of LPS induced a robust pulmonary pro-inflammatory response with endothelial barrier dysfunction and significantly enhanced ANG2 expression. The percentage number of TEMs, assessed by FACS analysis, was more than trebled compared to controls, with TEM count in lungs reaching more than 40% of all macrophages. Such distinct dynamic was absent in all other analyzed compartments (alveolar space, spleen, blood). Incubation of the monocytic cell line THP-1 with LPS or TNF-α resulted in a dose-dependent, significant upregulation of TIE2, suggesting that not recruitment from extra-pulmonary compartments but TIE2 upregulation in resident macrophages accounts for increased lung TEM frequencies. For the first time, our data provide evidence that the activity of TEMs changes at sites of acute inflammation.

(1) Background: This retrospective study focused on severe acute respiratory distress syndrome (ARDS) patients treated with veno-venous (VV) extracorporeal membrane oxygenation (ECMO) and who inhaled nitric oxide (NO) for pulmonary arterial hypertension (PAH) and/or right ventricular failure (RV failure). (2) Methods: Out of 662 ECMO-supported patients, 366 received VV ECMO, including 48 who inhaled NO. We examined the NO’s indications, dosing, duration, and the ability to lower PAH. We compared patients with and without inhaled NO in terms of mechanical ventilation duration, ECMO weaning, organ dysfunction, in-hospital mortality, and survival. (3) Results: Patients received 14.5 ± 5.5 ppm NO for 3 days with only one-third experiencing decreased pulmonary arterial pressure. They spent more time on VV ECMO, had a higher ECMO weaning failure frequency, and elevated severity scores (SAPS II and TIPS). A Kaplan–Meier analysis revealed reduced survival in the NO group. Multiple variable logistic regression indicated a twofold increased risk of death for ARDS patients on VV ECMO with NO. We observed no increase in continuous renal replacement therapy. (4) Conclusions: This study suggests that persistent PAH and/or RV failure is associated with poorer outcomes in severe ARDS patients on VV-ECMO, with an inhaled NO responder rate of only 30%, and it does not impact acute kidney failure rates.

Background/Objectives: Involving patients in the preoperative anaesthetic assessment (PAA) process can improve their understanding of risks and contribute to better postoperative recovery and outcomes. The iPREDICT study aims to investigate the feasibility of using an interactive consultation tool (ICT) to improve patient awareness of anaesthesia-related risks. Methods: This prospective, single-centre, randomised, placebo-controlled clinical study included patients scheduled for elective surgery under general or combined general and regional anaesthesia. Participants were randomly assigned to online anaesthesia risk education in the ICT group (intervention) or a control group that watched a video without anaesthetic risk content. Both groups received a face-to-face PAA and were assessed about anaesthetic risk knowledge after PAA and two days later. Results: A total of 373 participants were randomised, and 315 completed the assigned online module prior to their PAA. The proportion of male participants was higher (>60%). Most participants already had prior anaesthesia experience. After PAA, 243 patients completed the first risk recall #1 questionnaire, with the ICT group identifying significantly more correct risks than the control group (median 13.0 vs. 11.0, p < 0.05). In risk recall #2, conducted two days after the PAA, knowledge retention remained stable in the control group, while the experimental group showed further improvement (median 14.0 vs. 13.0, p < 0.05). Conclusions: Using the ICT significantly improved patients’ knowledge of anaesthesia-related risks. These results suggest that interactive patient education tools are a feasible and effective way to improve patients’ understanding of perioperative anaesthesia risks, potentially contributing to better outcomes, which needs to be addressed in future projects.