Assessment of spontaneous breathing during pressure controlled ventilation with superimposed spontaneous breathing using respiratory flow signal analysis.

Integrating spontaneous breathing into mechanical ventilation (MV) can speed up liberation from it and reduce its invasiveness. On the other hand, inadequate and asynchronous spontaneous breathing has the potential to aggravate lung injury. During use of airway-pressure-release-ventilation (APRV), the assisted breaths are difficult to measure. We developed an algorithm to differentiate the breaths in a setting of lung injury in spontaneously breathing ewes. We hypothesized that differentiation of breaths into spontaneous, mechanical and assisted is feasible using a specially developed for this purpose algorithm. Ventilation parameters were recorded by software that integrated ventilator output variables. The flow signal, measured by the EVITA® XL (Lübeck, Germany), was measured every 2 ms by a custom Java-based computerized algorithm (Breath-Sep). By integrating the flow signal, tidal volume (VT) of each breath was calculated. By using the flow curve the algorithm separated the different breaths and numbered them for each time point. Breaths were separated into mechanical, assisted and spontaneous. Bland Altman analysis was used to compare parameters. Comparing the values calculated by Breath-Sep with the data from the EVITA® using Bland-Altman analyses showed a mean bias of - 2.85% and 95% limits of agreement from - 25.76 to 20.06% for MVtotal. For respiratory rate (RR) RRset a bias of 0.84% with a SD of 1.21% and 95% limits of agreement from - 1.53 to 3.21% were found. In the cluster analysis of the 25th highest breaths of each group RRtotal was higher using the EVITA®. In the mechanical subgroup the values for RRspont and MVspont the EVITA® showed higher values compared to Breath-Sep. We developed a computerized method for respiratory flow-curve based differentiation of breathing cycle components during mechanical ventilation with superimposed spontaneous breathing. Further studies in humans and optimizing of this technique is necessary to allow for real-time use at the bedside.

Individualized Positive End-expiratory Pressure and Regional Gas Exchange in Porcine Lung Injury.

BACKGROUND: In acute respiratory failure elevated intraabdominal pressure aggravates lung collapse, tidal recruitment, and ventilation inhomogeneity. Low positive end-expiratory pressure (PEEP) may promote lung collapse and intrapulmonary shunting, whereas high PEEP may increase dead space by inspiratory overdistension. The authors hypothesized that an electrical impedance tomography-guided PEEP approach minimizing tidal recruitment improves regional ventilation and perfusion matching when compared to a table-based low PEEP/no recruitment and an oxygenation-guided high PEEP/full recruitment strategy in a hybrid model of lung injury and elevated intraabdominal pressure. METHODS: In 15 pigs with oleic acid-induced lung injury intraabdominal pressure was increased by intraabdominal saline infusion. PEEP was set in randomized order: (1) guided by a PEEP/inspired oxygen fraction table, without recruitment maneuver; (2) minimizing tidal recruitment guided by electrical impedance tomography after a recruitment maneuver; and (3) maximizing oxygenation after a recruitment maneuver. Single photon emission computed tomography was used to analyze regional ventilation, perfusion, and aeration. Primary outcome measures were differences in PEEP levels and regional ventilation/perfusion matching. RESULTS: Resulting PEEP levels were different (mean ± SD) with (1) table PEEP: 11 ± 3 cm H2O; (2) minimal tidal recruitment PEEP: 22 ± 3 cm H2O; and (3) maximal oxygenation PEEP: 25 ± 4 cm H2O; P < 0.001. Table PEEP without recruitment maneuver caused highest lung collapse (28 ± 11% vs. 5 ± 5% vs. 4 ± 4%; P < 0.001), shunt perfusion (3.2 ± 0.8 l/min vs. 1.0 ± 0.8 l/min vs. 0.7 ± 0.6 l/min; P < 0.001) and dead space ventilation (2.9 ± 1.0 l/min vs. 1.5 ± 0.7 l/min vs. 1.7 ± 0.8 l/min; P < 0.001). Although resulting in different PEEP levels, minimal tidal recruitment and maximal oxygenation PEEP, both following a recruitment maneuver, had similar effects on regional ventilation/perfusion matching. CONCLUSIONS: When compared to table PEEP without a recruitment maneuver, both minimal tidal recruitment PEEP and maximal oxygenation PEEP following a recruitment maneuver decreased shunting and dead space ventilation, and the effects of minimal tidal recruitment PEEP and maximal oxygenation PEEP were comparable.

Interprofessional two-man team approach for interhospital transport of ARDS-patients under extracorporeal membrane oxygenation: a 10 years retrospective observational cohort study.

BACKGROUND: 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. METHODS: 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. RESULTS: 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%. CONCLUSIONS: Initiation of extracorporeal membrane oxygenation and subsequent transport can be safely and efficiently performed by a two-man team with good outcome.

Effects of lung protective mechanical ventilation associated with permissive respiratory acidosis on regional extra-pulmonary blood flow in experimental ARDS.

BACKGROUND: Lung protective mechanical ventilation with limited peak inspiratory pressure has been shown to affect cardiac output in patients with ARDS. However, little is known about the impact of lung protective mechanical ventilation on regional perfusion, especially when associated with moderate permissive respiratory acidosis. We hypothesized that lung protective mechanical ventilation with limited peak inspiratory pressure and moderate respiratory acidosis results in an increased cardiac output but unequal distribution of blood flow to the different organs of pigs with oleic-acid induced ARDS. METHODS: Twelve pigs were enrolled, 3 died during instrumentation and induction of lung injury. Thus, 9 animals received pressure controlled mechanical ventilation with a PEEP of 5 cmH2O and limited peak inspiratory pressure (17 ± 4 cmH2O) versus increased peak inspiratory pressure (23 ± 6 cmH2O) in a crossover-randomized design and were analyzed. The sequence of limited versus increased peak inspiratory pressure was randomized using sealed envelopes. Systemic and regional hemodynamics were determined by double indicator dilution technique and colored microspheres, respectively. The paired student t-test and the Wilcoxon test were used to compare normally and not normally distributed data, respectively. RESULTS: Mechanical ventilation with limited inspiratory pressure resulted in moderate hypercapnia and respiratory acidosis (PaCO2 71 ± 12 vs. 46 ± 9 mmHg, and pH 7.27 ± 0.05 vs. 7.38 ± 0.04, p < 0.001, respectively), increased cardiac output (140 ± 32 vs. 110 ± 22 ml/min/kg, p<0.05) and regional blood flow in the myocardium, brain and spinal cord, adrenal and thyroid glands, the mucosal layers of the esophagus and jejunum, the muscularis layers of the esophagus and duodenum, and the gall and urinary bladders. Perfusion of kidneys, pancreas, spleen, hepatic arterial bed, and the mucosal and muscularis blood flow to the other evaluated intestinal regions remained unchanged. CONCLUSIONS: In this porcine model of ARDS mechanical ventilation with limited peak inspiratory pressure resulting in moderate respiratory acidosis was associated with an increase in cardiac output. However, the better systemic blood flow was not uniformly directed to the different organs. This observation may be of clinical interest in patients, e.g. with cardiac, renal and cerebral pathologies.

Extracorporeal Carbon Dioxide Removal Enhanced by Lactic Acid Infusion in Spontaneously Breathing Conscious Sheep.

BACKGROUND: The authors studied the effects on membrane lung carbon dioxide extraction (VCO2ML), spontaneous ventilation, and energy expenditure (EE) of an innovative extracorporeal carbon dioxide removal (ECCO2R) technique enhanced by acidification (acid load carbon dioxide removal [ALCO2R]) via lactic acid. METHODS: Six spontaneously breathing healthy ewes were connected to an extracorporeal circuit with blood flow 250 ml/min and gas flow 10 l/min. Sheep underwent two randomly ordered experimental sequences, each consisting of two 12-h alternating phases of ALCO2R and ECCO2R. During ALCO2R, lactic acid (1.5 mEq/min) was infused before the membrane lung. Caloric intake was not controlled, and animals were freely fed. VCO2ML, natural lung carbon dioxide extraction, total carbon dioxide production, and minute ventilation were recorded. Oxygen consumption and EE were calculated. RESULTS: ALCO2R enhanced VCO2ML by 48% relative to ECCO2R (55.3 ± 3.1 vs. 37.2 ± 3.2 ml/min; P less than 0.001). During ALCO2R, minute ventilation and natural lung carbon dioxide extraction were not affected (7.88 ± 2.00 vs. 7.51 ± 1.89 l/min, P = 0.146; 167.9 ± 41.6 vs. 159.6 ± 51.8 ml/min, P = 0.063), whereas total carbon dioxide production, oxygen consumption, and EE rose by 12% each (223.53 ± 42.68 vs. 196.64 ± 50.92 ml/min, 215.3 ± 96.9 vs. 189.1 ± 89.0 ml/min, 67.5 ± 24.0 vs. 60.3 ± 20.1 kcal/h; P less than 0.001). CONCLUSIONS: ALCO2R was effective in enhancing VCO2ML. However, lactic acid caused a rise in EE that made ALCO2R no different from standard ECCO2R with respect to ventilation. The authors suggest coupling lactic acid-enhanced ALCO2R with active measures to control metabolism.

Analysis of Patients with Severe ARDS on VV ECMO Treated with Inhaled NO: A Retrospective Observational Study.

(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.

Prevalence and prognostic relevance of invasive fungal disease during veno-arterial ECMO: A retrospective single-center study.

PURPOSE: To assess the prevalence and relevance of invasive fungal disease (IFD) during veno-arterial (V-A) extracorporeal membrane oxygenation (ECMO). METHODS: Retrospective analysis from January 2013 to November 2023 of adult V-A ECMO cases at a German University Hospital. Parameters relating to IFD, demographics, length of stay (LoS), days on ECMO and mechanical ventilation, prognostic scores and survival were assessed. Multivariable logistic regression analyses with IFD and death as dependent variables were performed. Outcome was assessed after propensity score matching IFD-patients to non-IFD-controls. RESULTS: 421 patients received V-A ECMO. 392 patients with full electronic datasets were included. The prevalence of IFD, invasive candidiasis and probable invasive pulmonary aspergillosis was 4.6%, 3.8% and 1.0%. Severity of acute disease, pre-existing moderate-to-severe renal disease and continuous kidney replacement therapy were predictive of IFD. In-hospital mortality (94% (17/18) compared to 67% (252/374) in non-IFD patients (p = 0.0156)) was predicted by female sex, SOFA score at admission, SAVE score and IFD (for IFD: OR: 8.31; CI: 1.60-153.18; p: 0.044). There was no difference in outcome after matching IFD-cases to non-IFD-controls. CONCLUSIONS: IFD are detected in about one in 20 patients on V-A ECMO, indicating mortality >90%. However, IFD do not contribute to prognosis in this population.

Estimation of Cardiac Output Under Veno-Venous Extracorporeal Membrane Oxygenation: Comparing Thermodilution Methods to 3D Echocardiography.

Thermodilution methods to determine cardiac output (CO) may be affected by veno-venous extracorporeal membrane oxygenation (ECMO). We compared CO estimations by pulmonary arterial thermodilution using a pulmonary arterial catheter (COPAC), transpulmonary thermodilution (COTPTD), and three-dimensional echocardiography (3DEcho) (CO3DEcho) in 18 patients under veno-venous ECMO. Comparisons between CO3DEcho and COPAC, and COTPTD were performed using correlation statistics and Bland-Altman analysis. Blood flow on ECMO support ranged from 4.3 to 5.8 L/min (median 4.9 L/min). Cardiac output measured with three-dimensional echocardiography was 5.2 L/min (3.8/5.9), COPAC was 7.3 L/min (5.9/7.9), and COTPTD was 7.3 L/min (6/8.2) (median [25%/75% percentile]). Bland-Altman analysis of CO3DEcho and COPAC revealed a mean bias of -2.06 L/min, with limits of agreement from -4.16 to 0.04 L/min. Bland-Altman analysis of CO3DEcho and COTPTD revealed a mean bias of -2.22 L/min, with limits of agreement from -4.18 to -0.25 L/min. We found a negative mean bias and negative limits of agreement between CO3DEcho and COPAC/COTPTD. We concluded an influence on the estimation of CO by thermodilution under ECMO most likely due to loss of indicator resulting in an overestimation of CO. Clinicians should consider this when monitoring thermodilution-based CO under ECMO.

Monitoring of Cerebral Oxygen Saturation in Interhospital Transport of Patients Receiving Extracorporeal Membrane Oxygenation.

Extracorporeal membrane oxygenation (ECMO) in acute respiratory distress syndrome (ARDS) is used to achieve oxygenation and protect lung ventilation. Near infrared spectroscopy (NIRS) measures cerebral regional tissue oxygenation (rSO 2 ) and may contribute to patient safety during interhospital transport under ECMO support. We evaluated 16 adult ARDS patients undergoing interhospital ECMO transport by measuring cerebral rSO 2 before and after initiation of ECMO support and continuously during transport. To compare peripheral oxygen saturation (SpO 2 ) measurement with rSO 2 , both parameters were analyzed. NIRS monitoring for initiation of ECMO and interhospital transport under ECMO support was feasible, and there was no significant difference in the percentage of achievable valid measurements over time between cerebral rSO 2 (88.4% [95% confidence interval {CI}, 81.3-95.0%]) and standard SpO 2 monitoring 91.7% (95% CI, 86.1-94.2%), p = 0.68. No change in cerebral rSO 2 was observed before 77% (73.5-81%) (median [interquartile range {IQR}]) and after initiation of ECMO support 78% (75-81%), p = 0.2. NIRS for cerebral rSO 2 measurement is feasible during ECMO initiation and interhospital transport. Achievement of valid measurements of cerebral rSO 2 was not superior to SpO 2 . In distinct patients ( e.g. , shock), measurement of cerebral rSO 2 may contribute to improvement of patient safety during interhospital ECMO transport.

COVID-19 Is an Independent Risk Factor for Detrimental Invasive Fungal Disease in Patients on Veno-Venous Extracorporeal Membrane Oxygenation: A Retrospective Study.

Invasive fungal disease (IFD) is associated with the mortality of patients on extracorporeal membrane oxygenation (ECMO). Several risk factors for IFD have been identified in patients with or without ECMO. Here, we assessed the relevance of coronavirus disease (COVID-19) for the occurrence of IFD in patients on veno-venous (V-V) ECMO for respiratory failure. In a retrospective analysis of all ECMO cases between January 2013 and December 2022 (2020-2022 for COVID-19 patients), active COVID-19 and the type, timing and duration of IFD were investigated. Demographics, hospital, ICU length of stay (LoS), duration of ECMO, days on invasive mechanical ventilation, prognostic scores (Respiratory ECMO Survival Prediction (RESP) score, Charlson Comorbidity Index (CCI), Therapeutic Intervention Scoring System (TISS)-10, Sequential Organ Failure Assessment (SOFA) score and Simplified Acute Physiology Score (SAPS)-II) and length of survival were assessed. The association of COVID-19 with IFD was investigated using propensity score matching and uni- and multivariable logistic regression analyses. We identified 814 patients supported with ECMO, and 452 patients were included in further analyses. The incidence of IFD was 4.8% and 11.0% in patients without and with COVID-19, respectively. COVID-19 status represented an independent risk factor for IFD (OR 4.30; CI 1.72-10.85; p: 0.002; multivariable regression analysis). In patients with COVID-19, 84.6% of IFD was candidemia and 15.4% represented invasive aspergillosis (IA). All of these patients died. In patients on V-V ECMO, we report that COVID-19 is an independent risk factor for IFD, which is associated with a detrimental prognosis. Further studies are needed to investigate strategies of antifungal therapy or prophylaxis in these patients.

Cardiovascular Magnetic Resonance in Survivors of Critical Illness: Cardiac Abnormalities Are Associated With Acute Kidney Injury.

Background The objective of this study was to investigate cardiac abnormalities in intensive care unit (ICU) survivors of critical illness and to determine whether temporary acute kidney injury (AKI) is associated with more pronounced findings on cardiovascular magnetic resonance. Methods and Results There were 2175 patients treated in the ICU (from 2015 until 2021) due to critical illness who were screened for study eligibility. Post-ICU patients without known cardiac disease were prospectively recruited from March 2021 to May 2022. Participants underwent cardiovascular magnetic resonance including assessment of cardiac function, myocardial edema, late gadolinium enhancement, and mapping including extracellular volume fraction. Student t test, Mann-Whitney U test, and χ2 tests were used. There were 48 ICU survivors (46±15 years of age, 28 men, 29 with AKI and continuous kidney replacement therapy, and 19 without AKI) and 20 healthy controls who were included. ICU survivors had elevated markers of myocardial fibrosis (T1: 995±31 ms versus 957±21 ms, P<0.001; extracellular volume fraction: 24.9±2.5% versus 22.8±1.2%, P<0.001; late gadolinium enhancement: 1% [0%-3%] versus 0% [0%-0%], P<0.001), more frequent focal late gadolinium enhancement lesions (21% versus 0%, P=0.03), and an impaired left ventricular function (eg, ejection fraction: 57±6% versus 60±5%, P=0.03; systolic longitudinal strain: 20.3±3.7% versus 23.1±3.5%, P=0.004) compared with healthy controls. ICU survivors with AKI had higher myocardial T1 (1002±33 ms versus 983±21 ms; P=0.046) and extracellular volume fraction values (25.6±2.6% versus 23.9±1.9%; P=0.02) compared with participants without AKI. Conclusions ICU survivors of critical illness without previously diagnosed cardiac disease had distinct abnormalities on cardiovascular magnetic resonance including signs of myocardial fibrosis and systolic dysfunction. Findings were more abnormal in participants who experienced AKI with necessity of continuous kidney replacement therapy during their ICU stay. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT05034588.

Measurement of Electrical Impedance Tomography-Based Regional Ventilation Delay for Individualized Titration of End-Expiratory Pressure.

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 (PEI), 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 PEI 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). PEI resulting from 9 mL/kg BW inflations were comparable with PEI 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 PEI and may reduce potential clinical risks.

Secondary ARDS Following Acute Pancreatitis: Is Extracorporeal Membrane Oxygenation Feasible or Futile?

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.

Role of acquired von Willebrand syndrome in the development of bleeding complications in patients treated with Impella RP devices.

Axial flow pumps are standard treatment in cases of cardiogenic shock and high-risk interventions in cardiology and cardiac surgery, although the optimal anticoagulation strategy remains unclear. We evaluated whether laboratory findings could predict bleeding complications and acquired von Willebrand syndrome (avWS) among patients who were treated using axial flow pumps. We retrospectively evaluated 60 consecutive patients who received Impella devices (Impella RP: n = 20, Impella CP/5.0: n = 40; Abiomed Inc., Danvers, USA) between January 2019 and December 2020. Thirty-two patients (53.3%) experienced major or fatal bleeding complications (Bleeding Academic Research Consortium score of > 3) despite intravenous heparin being used to maintain normal activated partial thromboplastin times (40-50 s). Extensive testing was performed for 28 patients with bleeding complications (87.5%). Relative to patients with left ventricular support, patients with right ventricular support were less likely to develop avWS (87.5% vs. 58.8%, p = 0.035). Bleeding was significantly associated with avWS (odds ratio [OR]: 20.8, 95% confidence interval [CI]: 3.3-128.5; p = 0.001) and treatment duration (OR: 1.3, 95% CI 1.09-1.55; p = 0.003). Patients with avWS had longer Impella treatment than patients without avWS (2 days [1-4.7 days] vs. 7.3 days [3.2-13.0 days]). Bleeding complications during Impella support were associated with avWS in our cohort, while aPTT monitoring was not sufficient to prevent bleeding complications. A more targeted anticoagulation monitoring might be needed for patients who receive Impella devices.

CT fatty muscle fraction as a new parameter for muscle quality assessment predicts outcome in venovenous extracorporeal membrane oxygenation.

Impaired skeletal muscle quality is a major risk factor for adverse outcomes in acute respiratory failure. However, conventional methods for skeletal muscle assessment are inapplicable in the critical care setting. This study aimed to determine the prognostic value of computed tomography (CT) fatty muscle fraction (FMF) as a biomarker of muscle quality in patients undergoing extracorporeal membrane oxygenation (ECMO). To calculate FMF, paraspinal skeletal muscle area was obtained from clinical CT and separated into areas of fatty and lean muscle based on densitometric thresholds. The cohort was binarized according to median FMF. Patients with high FMF displayed significantly increased 1-year mortality (72.7% versus 55.8%, P = 0.036) on Kaplan-Meier analysis. A multivariable logistic regression model was built to test the impact of FMF on outcome. FMF was identified as a significant predictor of 1-year mortality (hazard ratio per percent FMF, 1.017 [95% confidence interval, 1.002-1.033]; P = 0.031), independent of anthropometric characteristics, Charlson Comorbidity Index, Simplified Acute Physiology Score, Respiratory Extracorporeal Membrane Oxygenation Survival Prediction Score, and duration of ECMO support. To conclude, FMF predicted 1-year mortality independently of established clinical prognosticators in ECMO patients and may have the potential to become a new muscle quality imaging biomarker, which is available from clinical CT.

Extensive Therapeutic Drug Monitoring of Colistin in Critically Ill Patients Reveals Undetected Risks.

(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.

1H-NMR Metabolomics Identifies Significant Changes in Metabolism over Time in a Porcine Model of Severe Burn and Smoke Inhalation.

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.

Spontaneous breathing during airway pressure release ventilation in experimental lung injury: effects on hepatic blood flow.

OBJECTIVE: Positive pressure ventilation can affect systemic haemodynamics and regional blood flow distribution with negative effects on hepatic blood flow. We hypothesized that spontaneous breathing (SB) with airway pressure release ventilation (APRV) provides better systemic and hepatic blood flow than APRV without SB. DESIGN: Animal study with a randomized cross-over design. SETTING: Animal laboratory of Bonn University Hospital. SUBJECTS: Twelve pigs with oleic-acid-induced lung injury. INTERVENTIONS: APRV with or without SB in random order. Without SB, either the upper airway pressure limit or the ventilator rate was increased to maintain constant pH and PaCO2. MEASUREMENTS AND RESULTS: Systemic haemodynamics were determined by double-indicator dilution, organ blood flow by coloured microspheres. Systemic blood flow was best during APRV with SB. During APRV with SB blood flow (ml g(-1) min(-1)) was 0.91+/-0.26 (hepatic arterial), 0.29+/-0.05 (stomach), 0.64+/-0.08 (duodenum), 0.62+/-0.10 (jejunum), 0.53+/-0.07 (ileum), 0.53+/-0.07 (colon), 0.46+/-0.09 (pancreas) and 3.59+/-0.55 (spleen). During APRV without SB applying high P(aw) it decreased to 0.13+/-0.01 (stomach), 0.37+/-0.03 (duodenum), 0.29+/-0.03 (jejunum), 0.31+/-0.05 (ileum), 0.32+/-0.03 (colon) and 0.23+/-0.04 (pancreas) p<0.01, respectively. During APRV without SB applying same Paw limits it decreased to 0.18+/-0.03 (stomach, p<0.01), 0.47+/-0.06 (duodenum, p<0.05), 0.38+/-0.05 (jejunum, p<0.01), 0.36+/-0.03 (ileum, p<0.05), 0.39+/-0.05 (colon, p<0.05), and 0.27+/-0.04 (pancreas, p<0.01). Arterial liver blood flow did not change significantly when SB was abolished (0.55+/-0.11 and 0.63+/-0.11, respectively). CONCLUSIONS: Maintaining SB during APRV was associated with better systemic and pre-portal organ blood flow. Improvement in hepatic arterial blood flow was not significant.

[Alveolar ventilation and recruitment under lung protective ventilation]. / Alveoläre Ventilation und Rekrutierung unter lungenprotektiver Beatmung.

Goal of mechanical ventilation is to improve gas exchange and reduce work of breathing without contributing to further lung injury. Besides providing adequate EELV and thereby arterial oxygenation PEEP in addition to a reduction in tidal volume is required to prevent cyclic alveolar collapse and tidal recruitment and hence protective mechanical ventilation. Currently, there is no consensus if and if yes at which price alveolar recruitment with high airway pressures should be intended ("open up the lung"), or if it is more important to reduce the mechanical stress and strain to the lungs as much as possible ("keep the lung closed"). Potential of alveolar recruitment differs from patient to patient but also between lung regions. Potential for recruitment depends probably more on regional lung mechanics - especially on lung elastance - than on the underlying disease. Based on available data neither high PEEP nor other methods used for alveolar recruitment could demonstrate a survival benefit in patients with ARDS. These results may support an individualized titration of PEEP or other manoeuvres used for recruitment taking into consideration the regional effects. Bedside imaging techniques allowing titration of PEEP or other manoeuvres to prevent end-expiratory alveolar collapse (tidal recruitment) and inspiratory overinflation may be a promising development.

[Lung protective ventilation - protective effect of adequate supported spontaneous breathing]. / Assistierte Spontanatmung: physiologische Grundlagen und protektive Effekte.

Based on available data, it can be suggested that spontaneous breathing during ventilator support has not to be suppressed even in patients with severe pulmonary dysfunction if no contraindications are present. Experimental data do not support the contention that spontaneous breathing aggravates ventilator-induced lung injury. During spontaneous breathing increase in PTP is maximal in the depended lung areas in adjunct to the diaphragm and causes recruitment of initially atelectatic lung areas thereby avoiding cyclic alveolar collapse and reopening. This should result in a lung protective effect of adequate supported spontaneous breathing. Clinical data supported this belief demonstrating improvement in pulmonary gas exchange, systemic blood flow, and oxygen supply to the tissue and a decrease in days on ventilator support and duration of stay in the intensive care unit.