Carbon Dioxide Targets in Extracorporeal Membrane Oxygenation for Acute Respiratory Distress Syndrome.

Target values for arterial carbon dioxide tension (PaCO2) in extracorporeal membrane oxygenation (ECMO) for acute respiratory distress syndrome (ARDS) are unknown. We hypothesized that lower PaCO2 values on ECMO would be associated with lighter sedation. We used data from two independent patient cohorts with ARDS spending 1,177 days (discovery cohort, 69 patients) and 516 days (validation cohort, 70 patients) on ECMO and evaluated the associations between daily PaCO2, pH, and bicarbonate (HCO3) with sedation. Median PaCO2 was 41 (interquartile range [IQR] = 37-46) mm Hg and 41 (IQR = 37-45) mm Hg in the discovery and the validation cohort, respectively. Lower PaCO2 and higher pH but not bicarbonate (HCO3) served as significant predictors for reaching a Richmond Agitation Sedation Scale (RASS) target range of -2 to +1 (lightly sedated to restless). After multivariable adjustment for mortality, tracheostomy, prone positioning, vasoactive inotropic score, Simplified Acute Physiology Score (SAPS) II or Sequential Organ Failure Assessment (SOFA) Score and day on ECMO, only PaCO2 remained significantly associated with the RASS target range (adjusted odds ratio 1.1 [95% confidence interval (CI) = 1.01-1.21], p = 0.032 and 1.29 [95% CI = 1.1-1.51], p = 0.001 per mm Hg decrease in PaCO2 for the discovery and the validation cohort, respectively). A PaCO2 ≤40 mm Hg, as determined by the concordance probability method, was associated with a significantly increased probability of a sedation level within the RASS target range in both patient cohorts (adjusted odds ratio = 2.92 [95% CI = 1.17-7.24], p = 0.021 and 6.82 [95% CI = 1.50-31.0], p = 0.013 for the discovery and the validation cohort, respectively).

[COVID-19 in the intensive care unit]. / Intensivmedizinische Therapie von COVID-19.

The acute respiratory failure as well as ARDS (acute respiratory distress syndrome) have challenged clinicians since the initial description over 50 years ago. Various causes can lead to ARDS and therapeutic approaches for ARDS/ARF are limited to the support or replacement of organ functions and the prevention of therapy-induced consequences. In recent years, triggered by the SARS-CoV-2 pathogen, numerous cases of acute lung failure (C-ARDS) have emerged. The pathophysiological processes of classical ARDS and C-ARDS are essentially similar. In their final stages of inflammation, both lead to a disruption of the blood-air barrier. Treatment strategies for C-ARDS, like classical ARDS, focus on supporting or replacing organ functions and preventing consequential damage. This article summarizes the treatment strategies in the intensive care unit.

External Validation of the PREdiction of Survival on Extracorporeal Membrane Oxygenation Therapy (PRESET) Score: A Single Center Cohort Experience.

Acute respiratory distress syndrome (ARDS) is a life-threatening condition affecting >10% of intensive care unit (ICU) patients worldwide with a mortality of up to 59% depending on severity. Extracorporeal membrane oxygenation (ECMO) is a potentially life-saving procedure in severe ARDS but is technically and financially challenging. In recent years, various scoring systems have been proposed to select patients most likely to benefit from ECMO, with the PREdiction of Survival on ECMO Therapy (PRESET) score being one of the most used. We collected data from 283 patients with ARDS of various etiology who underwent veno-venous (V-V) ECMO therapy at a German tertiary care ICU from January 2012 to December 2022. Median age in the cohort was 56 years, and 64.31% were males. The in-hospital mortality rate was 50.88% (n = 144). The median (25%; 75% quartile) severity scores were 38 (31; 49) for Simplified Acute Physiology Score (SAPS) II, 12 (10; 13) for Sequential Organ Failure Assessment (SOFA) and 7 (5; 8) for PRESET. Simplified Acute Physiology Score-II displayed the best prognostic value (area under the receiver operating characteristic [AUROC]: 0.665 [confidence interval (CI): 0.574-0.756; p = 0.046]). Prediction performance was weak in all analyzed scores despite good calibration. Simplified Acute Physiology Score-II had the best discrimination after adjustment of our original cohort. The use of scores explored in this study for patient selection for eligibility for V-V ECMO is not recommendable.

Comparison of Serial and Parallel Connections of Membrane Lungs against Refractory Hypoxemia in a Mock Circuit.

Extracorporeal membrane oxygenation (ECMO) is an important rescue therapy method for the treatment of severe hypoxic lung injury. In some cases, oxygen saturation and oxygen partial pressure in the arterial blood are low despite ECMO therapy. There are case reports in which patients with such instances of refractory hypoxemia received a second membrane lung, either in series or in parallel, to overcome the hypoxemia. It remains unclear whether the parallel or serial connection is more effective. Therefore, we used an improved version of our full-flow ECMO mock circuit to test this. The measurements were performed under conditions in which the membrane lungs were unable to completely oxygenate the blood. As a result, only the photometric pre- and post-oxygenator saturations, blood flow and hemoglobin concentration were required for the calculation of oxygen transfer rates. The results showed that for a pre-oxygenator saturation of 45% and a total blood flow of 10 L/min, the serial connection of two identical 5 L rated oxygenators is 17% more effective in terms of oxygen transfer than the parallel connection. Although the idea of using a second membrane lung if refractory hypoxia occurs is intriguing from a physiological point of view, due to the invasiveness of the solution, further investigations are needed before this should be used in a wider clinical setting.

[When mechanical ventilation fails-Venovenous extracorporeal membrane oxygenation]. / Wenn maschinelle Beatmung nicht mehr ausreicht ­ venovenöse extrakorporale Membranoxygenierung.

Venovenous extracorporeal membrane oxygenation (VV-ECMO) is predominantly being used as a rescue strategy in patients with acute lung failure, suffering from severe oxygenation and/or decarboxylation impairment. Cannulas introduced into the central veins lead blood through a membrane oxygenator in which it is oxygenated via sweep gas (pO2 up to 600 mm Hg) flow, eliminating CO2. According to the largest randomized studies carried out so far, the two most important indications for VV-ECMO are hypoxic respiratory failure (paO2 < 80 mm Hg for more than 6 h) and refractory hypercapnia (pH < 7.25 und pCO2 > 60 mm Hg with a breathing frequency of >30/min) despite optimal protective mechanical ventilation settings (ARDS, Δp < 14 mbar, plateau pressure < 30 mbar, tidal volume VT < 6 ml/kg idealized body weight). Relative contraindications are life-limiting comorbidities and terminal pulmonary diseases that cannot be treated by lung transplantation. Advanced patient age is not regarded as an absolute contraindication, though it highly impacts ARDS survival rates, especially for pneumonia associated with coronavirus disease 2019 (COVID-19). The most frequent complications of VV-ECMO include bleeding, thrombus formation and rare cases of cannula-associated infections. Its use in nonintubated patients (awake ECMO) is possible in specific cases and has proven valuable as a bridge to lung transplant approach. Some ECMO centers offer cannulation of a patient at primary care hospitals, facilitating subsequent transport to the center (ECMO transport). The COVID-19 pandemic not only caused the number of VV-ECMO runs to skyrocket but has also drawn public attention to this extracorporeal procedure. Strict quality control to improve vvECMO outcomes according to the German hospital reform is urgently needed, especially so since the technique has a high demand in resources and bears significant risks when performed by untrained personnel.

Transfer of Veno-venous Extracorporeal Membrane Oxygenation Patients With COVID-19 Associated Acute Respiratory Distress Syndrome.

Interhospital transport of acute respiratory distress syndrome (ARDS) patients bears transport-associated risks. It is unknown how interhospital extracorporeal membrane oxygenation (ECMO) transfer of COVID-19 patients by mobile ECMO units affects ARDS mortality. We compared the outcome of 94 COVID-19 patients cannulated in primary care hospitals and retrieved by mobile ECMO-teams to that of 84 patients cannulated at five German ECMO centers. Patients were recruited from March 2020 to November 2021. Twenty-six transports were airborne, 68 were land-based. Age, sex, body-mass-index, Simplified Acute Physiology Score (SAPS) II, days invasively ventilated, and P/F-Ratio before ECMO initiation were similar in both groups. Counting only regional transports (≤250 km), mean transport distance was 139.5 km ± 17.7 km for helicopter (duration 52.5 ± 10.6 minutes) and 69.8 km ± 44.1 km for ambulance or mobile intensive care unit (duration 57.6 ± 29.4 minutes). Overall time of vvECMO support (20.4 ± 15.2 ECMO days for transported patients vs. 21.0 ± 20.5 for control, p = 0.83) and days invasively ventilated (27.9 ± 18.1 days vs. 32.6 ± 25.1 days, p = 0.16) were similar. Overall mortality did not differ between transported patients and controls (57/94 [61%] vs. 51/83 [61%], p = 0.43). COVID-19 patients cannulated and retrieved by mobile ECMO-teams have no excess risk compared with patients receiving vvECMO at experienced ECMO centers. Patients with COVID-19-associated ARDS, limited comorbidities, and no contraindication for ECMO should be referred early to local ECMO centers.

[Interhospital critical care transport]. / Interhospitaler Intensivtransport.

Critically ill patients in need of specialized diagnostic or therapeutic procedures, but are being cared for in a hospital without such equipment, have to be transferred to appropriate centers without discontinuation of current critical care (interhospital critical care transfer). These transfers are resource intensive, challenging, and require high logistical effort, which must be managed by a specialized and highly trained team, predeployment planning and efficient crew-resource management strategies. If planned adequately, interhospital critical care transfers can be performed safely without frequent adverse events. Beside routine interhospital critical care transfers, there are special missions (e.g., for patients in quarantine or supported by extracorporeal organ support) that might require adaption of the team composition or standard equipment. This article describes interhospital critical care transport missions including their different phases and special circumstances.

Daratumumab for a Patient With Refractory Antineutrophil Cytoplasmatic Antibody-Associated Vasculitis.

This case reports on a patient with antineutrophil cytoplasmatic antibody­associated vasculitis and severe pulmonary and cutaneous involvement who received conventional therapy that failed and who was rescued by daratumumab therapy.

[Interhospital critical care transport]. / Interhospitaler Intensivtransport.

Critically ill patients in need of specialized diagnostic or therapeutic procedures, but are being cared for in a hospital without such equipment, have to be transferred to appropriate centers without discontinuation of current critical care (interhospital critical care transfer). These transfers are resource intensive, challenging, and require high logistical effort, which must be managed by a specialized and highly trained team, predeployment planning and efficient crew-resource management strategies. If planned adequately, interhospital critical care transfers can be performed safely without frequent adverse events. Beside routine interhospital critical care transfers, there are special missions (e.g., for patients in quarantine or supported by extracorporeal organ support) that might require adaption of the team composition or standard equipment. This article describes interhospital critical care transport missions including their different phases and special circumstances.

Respiratory Physiology of COVID-19 and Influenza Associated Acute Respiratory Distress Syndrome.

Background: There is ongoing debate whether lung physiology of COVID-19-associated acute respiratory distress syndrome (ARDS) differs from ARDS of other origin. Objective: The aim of this study was to analyze and compare how critically ill patients with COVID-19 and Influenza A or B were ventilated in our tertiary care center with or without extracorporeal membrane oxygenation (ECMO). We ask if acute lung failure due to COVID-19 requires different intensive care management compared to conventional ARDS. Methods: 25 patients with COVID-19-associated ARDS were matched to a cohort of 25 Influenza patients treated in our center from 2011 to 2021. Subgroup analysis addressed whether patients on ECMO received different mechanical ventilation than patients without extracorporeal support. Results: Compared to Influenza-associated ARDS, COVID-19 patients had higher ventilatory system compliance (40.7 mL/mbar [31.8-46.7 mL/mbar] vs. 31.4 mL/mbar [13.7-42.8 mL/mbar], p = 0.198), higher ventilatory ratio (1.57 [1.31-1.84] vs. 0.91 [0.44-1.38], p = 0.006) and higher minute ventilation at the time of intubation (mean minute ventilation 10.7 L/min [7.2-12.2 L/min] for COVID-19 vs. 6.0 L/min [2.5-10.1 L/min] for Influenza, p = 0.013). There were no measurable differences in P/F ratio, positive end-expiratory pressure (PEEP) and driving pressures (ΔP). Respiratory system compliance deteriorated considerably in COVID-19 patients on ECMO during 2 weeks of mechanical ventilation (Crs, mean decrease over 2 weeks -23.87 mL/mbar ± 32.94 mL/mbar, p = 0.037) but not in ventilated Influenza patients on ECMO and less so in ventilated COVID-19 patients without ECMO. For COVID-19 patients, low driving pressures on ECMO were strongly correlated to a decline in compliance after 2 weeks (Pearson's R 0.80, p = 0.058). Overall mortality was insignificantly lower for COVID-19 patients compared to Influenza patients (40% vs. 48%, p = 0.31). Outcome was insignificantly worse for patients requiring veno-venous ECMO in both groups (50% mortality for COVID-19 on ECMO vs. 27% without ECMO, p = 0.30/56% vs. 34% mortality for Influenza A/B with and without ECMO, p = 0.31). Conclusion: The pathophysiology of early COVID-19-associated ARDS differs from Influenza-associated acute lung failure by sustained respiratory mechanics during the early phase of ventilation. We question whether intubated COVID-19 patients on ECMO benefit from extremely low driving pressures, as this appears to accelerate derecruitment and consecutive loss of ventilatory system compliance.

TNF-related apoptosis-inducing ligand, interferon gamma-induced protein 10, and C-reactive protein in predicting the progression of SARS-CoV-2 infection: a prospective cohort study.

BACKGROUND: Early prognostication of COVID-19 severity will potentially improve patient care. Biomarkers, such as TNF-related apoptosis-inducing ligand (TRAIL), interferon gamma-induced protein 10 (IP-10), and C-reactive protein (CRP), might represent possible tools for point-of-care testing and severity prediction. METHODS: In this prospective cohort study, we analyzed serum levels of TRAIL, IP-10, and CRP in patients with COVID-19, compared them with control subjects, and investigated the association with disease severity. RESULTS: A total of 899 measurements were performed in 132 patients (mean age 64 years, 40.2% females). Among patients with COVID-19, TRAIL levels were lower (49.5 vs 87 pg/ml, P = 0.0142), whereas IP-10 and CRP showed higher levels (667.5 vs 127 pg/ml, P <0.001; 75.3 vs 1.6 mg/l, P <0.001) than healthy controls. TRAIL yielded an inverse correlation with length of hospital and intensive care unit (ICU) stay, Simplified Acute Physiology Score II, and National Early Warning Score, and IP-10 showed a positive correlation with disease severity. Multivariable regression revealed that obesity (adjusted odds ratio [aOR] 5.434, 95% confidence interval [CI] 1.005-29.38), CRP (aOR 1.014, 95% CI 1.002-1.027), and peak IP-10 (aOR 1.001, 95% CI 1.00-1.002) were independent predictors of in-ICU mortality. CONCLUSIONS: We demonstrated a correlation between COVID-19 severity and TRAIL, IP-10, and CRP. Multivariable regression showed a role for IP-10 in predicting unfavourable outcomes, such as in-ICU mortality. TRIAL REGISTRATION: Clinicaltrials.gov, NCT04655521.

Injection of Recombinant Tissue Plasminogen Activator into Extracorporeal Membrane Oxygenators Postpones Oxygenator Exchange in COVID-19.

Coronavirus disease 2019 (COVID-19) has drastically increased the number of patients requiring extracorporeal life support. We investigate the efficacy and safety of low-dose recombinant tissue-type plasminogen activator (rtPA) injection into exhausted oxygenators to delay exchange in critically ill COVID-19 patients on veno-venous extracorporeal membrane oxygenation (V-V ECMO). Small doses of rtPA were injected directly into the draining section of a V-V ECMO circuit. We compared transmembrane pressure gradient, pump head efficiency, membrane arterial partial oxygen pressure, and membrane arterial partial carbon dioxide pressure before and after the procedure. Bleeding was compared with a matched control group of 20 COVID-19 patients on V-V ECMO receiving standard anticoagulation. Four patients received 16 oxygenator instillations with rtPA at 5, 10, or 20 mg per dose. Administration of rtPA significantly reduced transmembrane pressure gradient (Δ pm = 54.8 ± 18.1 mmHg before vs . 38.3 ± 13.3 mmHg after, p < 0.001) in a dose-dependent manner (Pearson's R -0.63, p = 0.023), allowing to delay oxygenator exchange, thus reducing the overall number of consumed oxygenators. rtPA increased blood flow efficiency η (1.20 ± 0.28 ml/revolution before vs . 1.24 ± 0.27 ml/r, p = 0.002). Lysis did not affect membrane blood gases or systemic coagulation. Minor bleeding occurred in 2 of 4 patients (50%) receiving oxygenator lysis as well as 19 of 20 control patients (95%). Lysis of ECMO oxygenators effectively delays oxygenator exchange, if exchange is indicated by an increase in transmembrane pressure gradient. Application of lysis did not result in higher bleeding incidences compared with anticoagulated patients on V-V ECMO for COVID-19.

First Use of a New Extracorporeal Membrane Oxygenation System in COVID19-Associated Adult Respiratory Distress Syndrome: The MobyBox Device.

In late 2020, during the second wave of COVID-19 in Germany, we started using the MobyBox, which is a novel fully pneumatically driven ECMO device, on a regular basis to meet the increasing demand for ECMO therapy. In this case series, we performed a retrospective chart review of seven patients with severe COVID-19-related acute respiratory distress syndrome (ARDS) requiring veno-venous (vv)-ECMO support with the MobyBox. During ECMO treatments we have observed no disadvantages in comparison to conventional ECMO systems. There were no system failures or adverse events directly attributable to the MobyBox system. Our data support that providing vv-ECMO with the MobyBox device is safe and feasible. Furthermore, our findings suggest that the MobyBox device might represent an advantage in terms of biocompatibility. Therefore, more data on this issue is needed to better understand how the pneumatically driven pump affects cellular blood components.

Killer immunoglobulin-like receptor 2DS5 is associated with recovery from coronavirus disease 2019.

BACKGROUND: Despite numerous advances in the identification of risk factors for the development of severe coronavirus disease 2019 (COVID-19), factors that promote recovery from COVID-19 remain unknown. Natural killer (NK) cells provide innate immune defense against viral infections and are known to be activated during moderate and severe COVID-19. Killer immunoglobulin-like receptors (KIR) mediate NK cell cytotoxicity through recognition of an altered MHC-I expression on infected target cells. However, the influence of KIR genotype on outcome of patients with COVID-19 has not been investigated so far. We retrospectively analyzed the outcome associations of NK cell count and KIR genotype of patients with COVID-19 related severe ARDS treated on our tertiary intensive care unit (ICU) between February and June 2020 and validated our findings in an independent validation cohort of patients with moderate COVID-19 admitted to our tertiary medical center. RESULTS: Median age of all patients in the discovery cohort (n = 16) was 61 years (range 50-71 years). All patients received invasive mechanical ventilation; 11 patients (68%) required extracorporeal membrane oxygenation (ECMO). Patients who recovered from COVID-19 had significantly higher median NK cell counts during the whole observational period compared to patients who died (121 cells/µL, range 16-602 cells/µL vs 81 cells/µL, range 6-227 cells/µL, p-value = 0.01). KIR2DS5 positivity was significantly associated with shorter time to recovery (21.6 ± 2.8 days vs. 44.6 ± 2.2 days, p-value = 0.01). KIR2DS5 positivity was significantly associated with freedom from transfer to ICU (0% vs 9%, p-value = 0.04) in the validation cohort which consisted of 65 patients with moderate COVID-19. CONCLUSION: NK cells and KIR genotype might have an impact on recovery from COVID-19.

Distinct Patterns of Blood Cytokines Beyond a Cytokine Storm Predict Mortality in COVID-19.

BACKGROUND: COVID-19 comprises several severity stages ranging from oligosymptomatic disease to multi-organ failure and fatal outcomes. The mechanisms why COVID-19 is a mild disease in some patients and progresses to a severe multi-organ and often fatal disease with respiratory failure are not known. Biomarkers that predict the course of disease are urgently needed. The aim of this study was to evaluate a large spectrum of established laboratory measurements. PATIENTS AND METHODS: Patients from the prospective PULMPOHOM and CORSAAR studies were recruited and comprised 35 patients with COVID-19, 23 with conventional pneumonia, and 28 control patients undergoing elective non-pulmonary surgery. Venous blood was used to measure the serum concentrations of 79 proteins by Luminex multiplex immunoassay technology. Distribution of biomarkers between groups and association with disease severity and outcomes were analyzed. RESULTS: The biomarker profiles between the three groups differed significantly with elevation of specific proteins specific for the respective conditions. Several biomarkers correlated significantly with disease severity and death. Uniform manifold approximation and projection (UMAP) analysis revealed a significant separation of the three disease groups and separated between survivors and deceased patients. Different models were developed to predict mortality based on the baseline measurements of several protein markers. A score combining IL-1ra, IL-8, IL-10, MCP-1, SCF and CA-9 was associated with significantly higher mortality (AUC 0.929). DISCUSSION: Several newly identified blood markers were significantly increased in patients with severe COVID-19 (AAT, EN-RAGE, myoglobin, SAP, TIMP-1, vWF, decorin) or in patients that died (IL-1ra, IL-8, IL-10, MCP-1, SCF, CA-9). The use of established assay technologies allows for rapid translation into clinical practice.

Acute Respiratory Distress Syndrome due to Mycoplasma pneumoniae Misinterpreted as SARS-CoV-2 Infection.

BACKGROUND: In 2020, a novel coronavirus caused a global pandemic with a clinical picture termed COVID-19, accounting for numerous cases of ARDS. However, there are still other infectious causes of ARDS that should be considered, especially as the majority of these pathogens are specifically treatable. Case Presentation. We present the case of a 36-year-old gentleman who was admitted to the hospital with flu-like symptoms, after completing a half-marathon one week before admission. As infection with SARS-CoV-2 was suspected based on radiologic imaging, the hypoxemic patient was immediately transferred to the ICU, where he developed ARDS. Empiric antimicrobial chemotherapy was initiated, the patient deteriorated further, therapy was changed, and the patient was transferred to a tertiary care ARDS center. As cold agglutinins were present, the hypothesis of an infection with SARS-CoV-2 was then questioned. Bronchoscopic sampling revealed Mycoplasma (M.) pneumoniae. When antimicrobial chemotherapy was adjusted, the patient recovered quickly. CONCLUSION: Usually, M. pneumoniae causes mild disease. When antimicrobial chemotherapy was adjusted, the patient recovered quickly. The case underlines the importance to adhere to established treatment guidelines, scrutinize treatment modalities, and not to forget other potential causes of severe pneumonia or ARDS.

Endoscopic lung volume reduction coils for patients with severe emphysema-a single-centre retrospective analysis.

OBJECTIVES: Patients with chronic obstructive pulmonary disease and lung emphysema may benefit from surgical or endoscopic lung volume reduction (ELVR). Previously reported outcomes of nitinol coil-based ELVR techniques have been ambiguous. The analysis was done to analyse outcomes of ELVR with nitinol coils in patients with severe pulmonary emphysema. METHODS: From September 2013 to November 2014, our centre performed a total of 41 coil implantations on 29 patients with severe emphysema. Coils were bronchoscopically placed during general anaesthesia. Twelve out of 29 patients received staged contralateral treatments up to 112 days later to avoid bilateral pneumothorax. Lung function and 6-min walking distance were assessed 1 week prior, 1 week after as well as 6-12 months after the procedure. Patients were followed up to 48 months after ELVR and overall mortality was compared to a historic cohort. RESULTS: While coil-based ELVR led to significant short-term improvement of vital capacity (VC, +0.14 ± 0.39 l, P = 0.032) and hyperinflation (Δ residual volume/total lung capacity -2.32% ± 6.24%, P = 0.022), no significant changes were observed in 6-min walking distance or forced expiratory volume in 1 s. Benefits were short-lived, with only 15.4% and 14.3% of patients showing sustained improvements in forced expiratory volume in 1 s or residual volume after 6 months. Adverse events included haemoptysis (40%) and pneumothorax (3.4%), major complications occurred in 6.9% of cases. Overall survival without lung transplant was 63.8% after 48 months following ELVR, differing insignificantly from what BODE indices of patients would have predicted as median 4-year survival (57%) at the time of ELVR treatment. CONCLUSIONS: ELVR with coils can achieve small and short-lived benefits in lung function at the cost of major complications in a highly morbid cohort. Treatment failed to improve 4-year overall survival. ELVR coils are not worthwhile the risk for most patients with severe emphysema.