Background: Despite being still invasive and challenging, technical improvement has resulted in broader and more frequent application of extracorporeal membrane oxygenation (ECMO), to prevent hypoxemia and to reduce invasiveness of mechanical ventilation (MV). Heparin-coated ECMO-circuits are currently standard of care, in addition to heparin based anticoagulation (AC) regimen guided by activated clotting time (ACT) or activated partial thromboplastin time (aPTT). Despite these advances, a reliable prediction of hemorrhage is difficult and the risk of hemorrhagic complication remains unfortunately high. We hypothesized, that there are coagulation parameters that are indices for a higher risk of hemorrhage under veno-venous (VV)-ECMO therapy. Methods: Data from 36 patients with severe respiratory failure treated with VV-ECMO at a University Hospital intensive care unit (ICU) were analyzed retrospectively. Patients were separated into two groups based on severity of hemorrhagic complications and transfusion requirements. The following data were collected: demographics, hemodynamic data, coagulation samples, transfusion requirements, change of ECMO-circuit during treatment and adverse effects, including hemorrhage and thrombosis. Results: In this study 74 hemorrhagic events were observed, one third of which were severe. Patients suffering from severe hemorrhage had a lower survival rate on VV-ECMO (43% vs. 91%; P=0.002) and in ICU (36% vs. 86%; P=0.002). SAPS II, factor VII and X were different between mild and severe hemorrhage group. Conclusions: Severe hemorrhage under VV-ECMO is associated with higher mortality. Only factor VII and X differed between groups. Further clinical studies are required to determine the timing of initiation and targets for AC therapies during VV-ECMO.

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.

Objective: To assess the feasibility of extracorporeal membrane oxygenation (ECMO) or life support (ECLS) as last resort life support therapy in patients with acute pancreatitis and subsequent secondary acute respiratory distress syndrome (ARDS). Methods: Retrospective analysis from January 2013, to April 2020, of ECMO patients with pancreatitis-induced ARDS at a German University Hospital. Demographics, hospital and ICU length of stay, duration of ECMO therapy, days on mechanical ventilation, fluid balance, need for decompressive laparotomy, amount of blood products, prognostic scores (CCI (Charlson Comorbidity Index), SOFA (Sequential Organ Failure Assessment), RESP(Respiratory ECMO Survival Prediction), SAVE (Survival after Veno-Arterial ECMO)), and the total known length of survival were assessed. Results: A total of n = 495 patients underwent ECMO. Eight patients with acute pancreatitis received ECLS (seven veno-venous, one veno-arterial). Five (71%) required decompressive laparotomy as salvage therapy due to abdominal hypertension. Two patients with acute pancreatitis (25%) survived to hospital discharge. The overall median length of survival was 22 days. Survivors required less fluid in the first 72 h of ECMO support and showed lower values for all prognostic scores. Conclusion: ECLS can be performed as a rescue therapy in patients with pancreatitis and secondary ARDS, but nevertheless mortality remains still high. Thus, this last-resort therapy may be best suited for patients with fewer pre-existing comorbidities and no other organ failure.

Burn injury initiates a hypermetabolic response leading to muscle catabolism and organ dysfunction but has not been well-characterized by high-throughput metabolomics. We examined changes in metabolism over the first 72 h post-burn using proton nuclear magnetic resonance (¹H-NMR) spectroscopy and serum from a porcine model of severe burn injury. We sought to quantify the changes in metabolism that occur over time in response to severe burn and smoke inhalation in this preliminary study. Fifteen pigs received 40% total body surface area (TBSA) burns with additional pine bark smoke inhalation. Arterial blood was drawn at baseline (pre-burn) and every 24 h until 72 h post-injury or death. The aqueous portion of each serum sample was analyzed using ¹H-NMR spectroscopy and metabolite concentrations were used for principal component analysis (PCA). Thirty-eight metabolites were quantified in 39 samples. Of these, 31 showed significant concentration changes over time (p < 0.05). PCA revealed clustering of samples by time point on a 2D scores plot. The first 48 h post-burn were characterized by high concentrations of histamine, alanine, phenylalanine, and tyrosine. Later timepoints were characterized by rising concentrations of 2-hydroxybutyrate, 3-hydroxybutyrate, acetoacetate, and isovalerate. No significant differences in metabolism related to mortality were observed. Our work highlights the accumulation of organic acids resulting from fatty acid catabolism and oxidative stress. Further studies will be required to relate accumulation of the four organic carboxylates identified in this analysis to outcomes from burn injury.

Rationale: Individualized positive end-expiratory pressure (PEEP) titration might be beneficial in preventing tidal recruitment. To detect tidal recruitment by electrical impedance tomography (EIT), the time disparity between the regional ventilation curves (regional ventilation delay inhomogeneity [RVDI]) can be measured during controlled mechanical ventilation when applying a slow inflation of 12 mL/kg of body weight (BW). However, repeated large slow inflations may result in high end-inspiratory pressure (P_EI), which might limit the clinical applicability of this method. We hypothesized that PEEP levels that minimize tidal recruitment can also be derived from EIT-based RVDI through the use of reduced slow inflation volumes. Methods: Decremental PEEP trials were performed in 15 lung-injured pigs. The PEEP level that minimized tidal recruitment was estimated from EIT-based RVDI measurement during slow inflations of 12, 9, 7.5, or 6 mL/kg BW. We compared RVDI and P_EI values resulting from different slow inflation volumes and estimated individualized PEEP levels. Results: RVDI values from slow inflations of 12 and 9 mL/kg BW showed excellent linear correlation (R² = 0.87, p < 0.001). Correlations decreased for RVDI values from inflations of 7.5 (R² = 0.68, p < 0.001) and 6 (R² = 0.42, p < 0.001) mL/kg BW. Individualized PEEP levels estimated from 12 and 9 mL/kg BW were comparable (bias −0.3 cm H₂O ± 1.2 cm H₂O). Bias and scatter increased with further reduction in slow inflation volumes (for 7.5 mL/kg BW, bias 0 ± 3.2 cm H₂O; for 6 mL/kg BW, bias 1.2 ± 4.0 cm H₂O). P_EI resulting from 9 mL/kg BW inflations were comparable with P_EI during regular tidal volumes. Conclusions: PEEP titration to minimize tidal recruitment can be individualized according to EIT-based measurement of the time disparity of regional ventilation courses during slow inflations with low inflation volumes_. This sufficiently decreases P_EI and may reduce potential clinical risks.