A Mortality Prediction Score for Patients With Veno-Venous Extracorporeal Membrane Oxygenation (VV-ECMO): The PREDICT VV-ECMO Score.

Mortality prediction for patients with the severe acute respiratory distress syndrome (ARDS) supported with veno-venous extracorporeal membrane oxygenation (VV-ECMO) is challenging. Clinical variables at baseline and on day 3 after initiation of ECMO support of all patients treated from October 2010 through April 2020 were analyzed. Multivariate logistic regression analysis was used to identify score variables. Internal and external (Monza, Italy) validation was used to evaluate the predictive value of the model. Overall, 272 patients could be included for data analysis and creation of the PREDICT VV-ECMO score. The score comprises five parameters (age, lung fibrosis, immunosuppression, cumulative fluid balance, and ECMO sweep gas flow on day 3). Higher score values are associated with a higher probability of hospital death. The score showed favorable results in derivation and external validation cohorts (area under the receiver operating curve, AUC derivation cohort 0.76 [95% confidence interval, CI, 0.71-0.82] and AUC validation cohort 0.74 [95% CI, 0.67-0.82]). Four risk classes were defined: I ≤ 30, II 31-60, III 61-90, and IV ≥ 91 with a predicted mortality of 28.2%, 56.2%, 84.8%, and 96.1%, respectively. The PREDICT VV-ECMO score suggests favorable performance in predicting hospital mortality under ongoing ECMO support providing a sound basis for further evaluation in larger cohorts.

Carboxyhemoglobin (CO-Hb) Correlates with Hemolysis and Hospital Mortality in Extracorporeal Membrane Oxygenation: A Retrospective Registry.

Background: Patients supported with extracorporeal membrane oxygenation (ECMO) may develop elevated carboxyhemoglobin (CO-Hb), a finding described in the context of hemolysis. Clinical relevance of elevated CO-Hb in ECMO is unclear. We therefore investigated the prognostic relevance of CO-Hb during ECMO support. Methods: Data derives from a retrospective single-center registry study. All ECMO patients in a medical ICU from October 2010 through December 2019 were considered. Peak arterial CO-Hb value during ECMO support and median CO-Hb values determined by point-of-care testing for distinct time intervals were determined. Groups were divided by CO-Hb (<2% or ≥2%). The primary endpoint was hospital survival. Results: A total of 729 patients with 59,694 CO-Hb values met the inclusion criteria. Median age (IQR) was 59 (48−68) years, 221/729 (30.3%) were female, and 278/729 (38.1%) survived until hospital discharge. Initial ECMO configuration was veno-arterial in 431/729 (59.1%) patients and veno-venous in 298/729 (40.9%) patients. Markers for hemolysis (lactate dehydrogenase, bilirubin, hemolysis index, and haptoglobin) all correlated significantly with higher CO-Hb (p < 0.001, respectively). Hospital survival was significantly higher in patients with CO-Hb < 2% compared to CO-Hb ≥ 2%, evaluating time periods 24−48 h (48.6% vs. 35.2%, p = 0.003), 48−72 h (51.5% vs. 36.8%, p = 0.003), or >72 h (56.9% vs. 31.1%, p < 0.001) after ECMO cannulation. Peak CO-Hb was independently associated with lower hospital survival after adjustment for confounders. Conclusions: In ECMO, CO-Hb correlates with hemolysis and hospital survival. If high CO-Hb measured should trigger a therapeutic intervention in order to reduce hemolysis has to be investigated in prospective trials.

Annual hospital procedural volume and outcome in extracorporeal membrane oxygenation for respiratory failure.

BACKGROUND: The hospital mortality of patients suffering from pulmonary failure requiring venovenous extracorporeal membrane oxygenation (V-V ECMO) or extracorporeal carbon dioxide removal (ECCO2 R) is high. It is unclear whether outcome correlates with a hospital's annual procedural volume. METHODS: Data on all V-V ECMO and ECCO2 R cases treated from 2007 to 2019 were retrieved from the German Institute for Medical Documentation and Information. Comorbidities and outcomes were assessed by DRG, OPS, and ICD codes. The study population was divided into 5 groups depending on annual hospital V-V ECMO and ECCO2 R volumes (<10 cases; 10-19 cases; 20-29 cases; 30-49 cases; ≥50 cases). Primary outcome was hospital mortality. RESULTS: A total of 25 096 V-V ECMO and 3607 ECCO2 R cases were analyzed. V-V ECMO hospitals increased from 89 in 2007 to 214 in 2019. Hospitals handling <10 cases annually increased especially (64 in 2007 to 149 in 2019). V-V ECMO cases rose from 807 in 2007 to 2597 in 2019. Over 50% of cases were treated in hospitals handling ≥30 cases annually. Hospital mortality was independent of the annual hospital procedural volume (55.3%; 61.3%; 59.8%; 60.2%; 56.3%, respectively, p = 0.287). We detected no differences when comparing hospitals handling <30 cases to those with ≥30 annually (p = 0.659). The numbers of ECCO2 R hospitals and cases has dropped since 2011 (287 in 2007 to 48 in 2019). No correlation between annual hospital procedural volume and hospital mortality was identified (p = 0.914). CONCLUSION: The number of hospitals treating patients requiring V-V ECMO and V-V ECMO cases rose from 2007 to 2019, while ECCO2 R hospitals and their case numbers decreased. We detected no correlation between annual hospital V-V ECMO or ECCO2 R volume and hospital mortality.

Key characteristics impacting survival of COVID-19 extracorporeal membrane oxygenation.

BACKGROUND: Severe COVID-19 induced acute respiratory distress syndrome (ARDS) often requires extracorporeal membrane oxygenation (ECMO). Recent German health insurance data revealed low ICU survival rates. Patient characteristics and experience of the ECMO center may determine intensive care unit (ICU) survival. The current study aimed to identify factors affecting ICU survival of COVID-19 ECMO patients. METHODS: 673 COVID-19 ARDS ECMO patients treated in 26 centers between January 1st 2020 and March 22nd 2021 were included. Data on clinical characteristics, adjunct therapies, complications, and outcome were documented. Block wise logistic regression analysis was applied to identify variables associated with ICU-survival. RESULTS: Most patients were between 50 and 70 years of age. PaO2/FiO2 ratio prior to ECMO was 72 mmHg (IQR: 58-99). ICU survival was 31.4%. Survival was significantly lower during the 2nd wave of the COVID-19 pandemic. A subgroup of 284 (42%) patients fulfilling modified EOLIA criteria had a higher survival (38%) (p = 0.0014, OR 0.64 (CI 0.41-0.99)). Survival differed between low, intermediate, and high-volume centers with 20%, 30%, and 38%, respectively (p = 0.0024). Treatment in high volume centers resulted in an odds ratio of 0.55 (CI 0.28-1.02) compared to low volume centers. Additional factors associated with survival were younger age, shorter time between intubation and ECMO initiation, BMI > 35 (compared to < 25), absence of renal replacement therapy or major bleeding/thromboembolic events. CONCLUSIONS: Structural and patient-related factors, including age, comorbidities and ECMO case volume, determined the survival of COVID-19 ECMO. These factors combined with a more liberal ECMO indication during the 2nd wave may explain the reasonably overall low survival rate. Careful selection of patients and treatment in high volume ECMO centers was associated with higher odds of ICU survival. TRIAL REGISTRATION: Registered in the German Clinical Trials Register (study ID: DRKS00022964, retrospectively registered, September 7th 2020, https://www.drks.de/drks_web/navigate.do?navigationId=trial.HTML&TRIAL_ID=DRKS00022964 .

Extracorporeal membrane oxygenation during the first three waves of the coronavirus disease 2019 pandemic: A retrospective single-center registry study.

BACKGROUND: Despite increasing knowledge about the optimal treatment for patients with severe COVID-19, data from different cohorts suggested that survival of patients treated with ECMO seemed to decline over the course of the pandemic. METHODS: In this non-interventional retrospective single-center registry study we analyzed all consecutive patients tested positive for SARS-CoV-2 infection and supported with VV ECMO in our center during the first three waves of the pandemic. From March 2020 through June 2021, 59 patients have been included. RESULTS: Overall 90-day survival was 32%. Besides changes in drug treatment for COVID-19 and a lower PaO2 /FiO2 ratio before ECMO initiation during the third wave, all other patient baseline characteristics were similar during the three waves. Survival rate was highest during the first wave and lowest during the third wave, yet this difference was not statistically significant. CONCLUSIONS: VV ECMO has shown to be a feasible and safe support option for patients with severe respiratory failure due to COVID-19. The results from this single-center study confirm findings from other cohorts showing declining survival rates of patients treated with VV ECMO during the COVID-19 pandemic, however, the specific reasons for this finding remain unclear.

Advantages of score-based delirium detection compared to a clinical delirium assessment-a retrospective, monocentric cohort study.

PURPOSE: Delirium is an underdiagnosed complication on intensive care units (ICU). We hypothesized that a score-based delirium detection using the Nudesc score identifies more patients compared to a traditional diagnosis of delirium by ICU physicians. METHODS: In this retrospective study, all patients treated on a general medical ICU with 30 beds in a university hospital in 2019 were analyzed. Primary outcome was a documented physician diagnosis of delirium, or a delirium score ≥2 using the Nudesc. RESULTS: In 205/943 included patients (21.7%), delirium was diagnosed by ICU physicians compared to 438/943 (46.4%; ratio 2.1) by Nudesc≥2. Both assessments were independent predictors of ICU stay (p<0.01). The physician diagnosis however was no independent predictor of mortality (OR 0.98 (0.57-1.72); p = 0.989), in contrast to the score-based diagnosis (OR 2.31 (1.30-4.10); p = 0.004). Subgroup analysis showed that physicians underdiagnosed delirium in case of hypoactive delirium and delirium in patients with female gender and in patients with an age below 60 years. CONCLUSION: Delirium in patients with hypoactive delirium, female patients and those below 60 years was underdiagnosed by physicians. The score-based delirium diagnosis detected delirium more frequently and correlated with ICU mortality and stay.

Long-term survival and health-related quality of life in patients with severe acute respiratory distress syndrome and veno-venous extracorporeal membrane oxygenation support.

BACKGROUND: There is limited information about the long-term outcome of patients suffering from acute respiratory distress syndrome (ARDS) supported with veno-venous extracorporeal membrane oxygenation (VV ECMO). Most studies focused on short- to mid-term follow-up. We aimed to investigate long-term survival and health-related quality of life (HRQL) in these patients. METHODS: We report retrospective data from a single-centre registry of patients with severe ARDS treated with VV ECMO at the Interdisciplinary Medical Intensive Care Unit at the Medical Centre, University of Freiburg, Germany, between 10/2010 and 06/2019. Follow-up data of all patients that survived the index hospitalisation were collected by telephone interviews from 02/2020 till 09/2020. Long-term survival, HRQL (Short-Form Health Survey-36 (SF-36), St. Georges Respiratory Questionnaire (SGRQ), Hospital Anxiety and Depression Scale (HADS)) and the return to work rate were documented. RESULTS: In total, 289 patients were treated with VV ECMO during the study period (median age 55 years, 67% males, hospital survival 45%). After a median duration of 3.9 years, follow-up assessment was complete in 94 of 129 hospital survivors (73%). Fifty-three patients completed the HRQL assessment. Hospital survivors showed a high 6- and 12-month survival rate (89% and 85%, respectively). Estimated survival rate of those discharged alive from ICU was 68.5% (95%-CI 56.9-80.1%) after 9.7 years. These patients reported high levels of HRQL (median SF-36 total score 73) and only few pulmonary (median SGRQ total score 19) and mental limitations (median HAD-D score 2 and HAD-A score 3). In total, 80% of the patients were able to resume employment. CONCLUSION: This analysis of VV ECMO patients showed favourable long-term survival and high levels of HRQL suggesting promising prospects for VV ECMO survivors.

Delirium in Critically Ill Patients with and without COVID-19-A Retrospective Analysis.

BACKGROUND: Delirium complicating the course of Intensive care unit (ICU) therapy is a known driver of morbidity and mortality. It has been speculated that infection with the neurotrophic SARS-CoV-2 might promote delirium. METHODS: Retrospective registry analysis including all patients treated at least 48 h on a medical intensive care unit. The primary endpoint was development of delirium as diagnosed by Nursing Delirium screening scale ≥2. Results were confirmed by propensity score matching. RESULTS: 542 patients were included. The primary endpoint was reached in 352/542 (64.9%) patients, without significant differences between COVID-19 patients and non-COVID-19 patients (51.4% and 65.9%, respectively, p = 0.07) and correlated with prolonged ICU stay in both groups. In a subgroup of patients with ICU stay >10 days delirium was significantly lower in COVID-19 patients (p ≤ 0.01). After adjustment for confounders, COVID-19 correlated independently with less ICU delirium (p ≤ 0.01). In the propensity score matched cohort, patients with COVID-19 had significantly lower delirium incidence compared to the matched control patients (p ≤ 0.01). CONCLUSION: Delirium is frequent in critically ill patients with and without COVID-19 treated at an intensive care unit. Data suggests that COVID-19 itself is not a driver of delirium per se.

Conservative management of COVID-19 associated hypoxaemia.

This correspondence argues that data presented previously cannot justify a novel approach for treating hypoxic patients with severe #COVID19 https://bit.ly/3dLaPlk.

Admission blood glucose level and outcome in patients requiring venoarterial extracorporeal membrane oxygenation.

BACKGROUND: Patients with cardiogenic shock or cardiac arrest undergoing venoarterial extracorporeal membrane oxygenation (V-A ECMO) frequently present with blood glucose levels out of normal range. The clinical relevance of such findings in the context of V-A ECMO is unknown. We therefore investigated the prognostic relevance of blood glucose at time of cannulation for V-A ECMO. METHODS: We conducted a single-center retrospective registry study. All patients receiving V-A ECMO from October 2010 to January 2020 were included if blood glucose level at time of cannulation were documented. Patients were divided in five groups according to the initial blood glucose level ranging from hypoglycemic (< 80 mg/dl), normoglycemic (80-140 mg/dl), to mild (141-240 mg/dl), moderate (241-400 mg/dl), and severe (> 400 mg/dl) hyperglycemia, respectively. Clinical presentation, arterial blood gas analysis, and survival were compared between the groups. RESULTS: 392 patients met inclusion criteria. Median age was 62 years (51.5-70.0), SAPS II at admission was 54 (43.5-63.0), and 108/392 (27.6%) were female. 131/392 were discharged alive (hospital survival 33.4%). At time of cannulation, survivors had higher pH, hemoglobin, calcium, bicarbonate but lower potassium and lactate levels compared to non-survivors (all p < 0.01). Outcome of patients diagnosed with particularly high (> 400 mg/dl) and low (< 80 mg/dl) blood glucose at time of V-A ECMO cannulation, respectively, was worse compared to patients with normoglycemic, mildly or moderately elevated values (p = 0.02). Glucose was independently associated with poor outcome after adjustment for other predictors of survival and persisted in all investigated subgroups. CONCLUSION: Arterial blood glucose at time of V-A ECMO cannulation predicts in-hospital survival of patients with cardiac shock or after ECPR. Whether dysglycemia represents a potential therapeutic target requires further evaluation in prospective studies.

Cytokine adsorption in patients with severe COVID-19 pneumonia requiring extracorporeal membrane oxygenation (CYCOV): a single centre, open-label, randomised, controlled trial.

BACKGROUND: We sought to clarify the benefit of cytokine adsorption in patients with COVID-19 supported with venovenous extracorporeal membrane oxygenation (ECMO). METHODS: We did a single-centre, open-label, randomised, controlled trial to investigate cytokine adsorption in adult patients with severe COVID-19 pneumonia requiring ECMO. Patients with COVID-19 selected for ECMO at the Freiburg University Medical Center (Freiburg, Germany) were randomly assigned (1:1) to receive cytokine adsorption using the CytoSorb device or not. Randomisation was computer-generated, allocation was concealed by opaque, sequentially numbered sealed envelopes. The CytoSorb device was incorporated into the ECMO circuit before connection to the patient circuit, replaced every 24 h, and removed after 72 h. The primary endpoint was serum interleukin-6 (IL-6) concentration 72 h after initiation of ECMO analysed by intention to treat. Secondary endpoints included 30-day survival. The trial is registered with ClinicalTrials.gov (NCT04324528) and the German Clinical Trials Register (DRKS00021300) and is closed. FINDINGS: From March 29, 2020, to Dec 29, 2020, of 34 patients assessed for eligibility, 17 (50%) were treated with cytokine adsorption and 17 (50%) without. Median IL-6 decreased from 357·0 pg/mL to 98·6 pg/mL in patients randomly assigned to cytokine adsorption and from 289·0 pg/mL to 112·0 pg/mL in the control group after 72 h. One patient in each group died before 72 h. Adjusted mean log IL-6 concentrations after 72 h were 0·30 higher in the cytokine adsorption group (95% CI -0·70 to 1·30, p=0·54). Survival after 30 days was three (18%) of 17 with cytokine adsorption and 13 (76%) of 17 without cytokine adsorption (p=0·0016). INTERPRETATION: Early initiation of cytokine adsorption in patients with severe COVID-19 and venovenous ECMO did not reduce serum IL-6 and had a negative effect on survival. Cytokine adsorption should not be used during the first days of ECMO support in COVID-19. FUNDING: None.

Mode of Death after Extracorporeal Cardiopulmonary Resuscitation.

INTRODUCTION: Extracorporeal cardiopulmonary resuscitation (ECPR) might be a lifesaving therapy for patients with cardiac arrest and no return of spontaneous circulation during advanced life support. However, even with ECPR, mortality of these severely sick patients is high. Little is known on the exact mode of death in these patients. METHODS: Retrospective registry analysis of all consecutive patients undergoing ECPR between May 2011 and May 2020 at a single center. Mode of death was judged by two researchers. RESULTS: A total of 274 ECPR cases were included (age 60.0 years, 47.1% shockable initial rhythm, median time-to-extracorporeal membrane oxygenation (ECMO) 53.8min, hospital survival 25.9%). The 71 survivors had shorter time-to-ECMO durations (46.0 ± 27.9 vs. 56.6 ± 28.8min, p < 0.01), lower initial lactate levels (7.9 ± 4.5 vs. 11.6 ± 8.4 mg/dL, p < 0.01), higher PREDICT-6h (41.7 ± 17.0% vs. 25.3 ± 19.0%, p < 0.01), and SAVE (0.4 ± 4.8 vs. -0.8 ± 4.4, p < 0.01) scores. Most common mode of death in 203 deceased patients was therapy resistant shock in 105/203 (51.7%) and anoxic brain injury in 69/203 (34.0%). Comparing patients deceased with shock to those with cerebral damage, patients with shock were significantly older (63.2 ± 11.5 vs. 54.3 ± 16.5 years, p < 0.01), more frequently resuscitated in-hospital (64.4% vs. 29.9%, p < 0.01) and had shorter time-to-ECMO durations (52.3 ± 26.8 vs. 69.3 ± 29.1min p < 0.01). CONCLUSIONS: Most patients after ECPR decease due to refractory shock. Older patients with in-hospital cardiac arrest might be prone to development of refractory shock. Only a minority die from cerebral damage. Research should focus on preventing post-CPR shock and treating the shock in these patients.

Impact of pulse pressure on clinical outcome in extracorporeal cardiopulmonary resuscitation (eCPR) patients.

BACKGROUND: Hemodynamic response to successful extracorporeal cardiopulmonary resuscitation (eCPR) is not uniform. Pulse pressure (PP) as a correlate for myocardial damage or recovery from it, might be a valuable tool to estimate the outcome of these patients. METHODS: We report retrospective data of a single-centre registry of eCPR patients, treated at the Interdisciplinary Medical Intensive Care Unit at the Medical Centre, University of Freiburg, Germany, between 01/2017 and 01/2020. The association between PP of the first 10 days after eCPR and hospital survival was investigated. Moreover, patients were divided into three groups according to their PP [low (0-9 mmHg), mid (10-29 mmHg) and high (≥ 30 mmHg)] at each time point. RESULTS: One hundred forty-three patients (age 63 years, 74.1% male, 40% OHCA, average low flow time 49 min) were analysed. Overall hospital survival rate was 28%. A low PP both early after eCPR (after 1, 3, 6 and 12 h) and after day 1 to day 8 was associated with reduced hospital survival. At each time point (1 h to day 5) the classification of patients into a low, mid and high PP group was able to categorize the patients for a low (5-20%), moderate (20-40%) and high (50-70%) survival rate. A multivariable analysis showed that the mean PP of the first 24 h was an independent predictor for survival (p = 0.008). CONCLUSION: In this analysis, PP occurred to be a valuable parameter to estimate survival and maybe support clinical decision making in the further course of patients after eCPR.

Case Report: Refusal of an Veno-Arterial Extracorporeal Membrane Oxygenation Due to Malignant Disease? - An Extremely Rare Form of Cardiac Involvement in Acute Myeloid Leukemia.

We report here on a 61-year-old patient with acute right heart failure of unclear etiology. Echocardiography revealed a myocardial mass infiltrating the heart, though, we assumed a cardiac lymphoma. A VA-ECMO was implanted as bridging for diagnosis and therapy. Our patient received chemotherapy, under which the tumor (of unknown etiology at this point) reached a partial remission. Nine months after first admission the patient developed acute myeloid leukemia with DNMT3a and TET2 mutations. Retrospective analysis of the cardiac biopsy revealed the identical mutations and matched with the diagnosis of an extremely rare primary extramedullary manifestation of an AML (myelosarcoma). The patient received induction-chemotherapy and was planned for consolidating allogeneic stem cell transplantation. From this case, we conclude that an extracorporeal therapy should be discussed in selected patients even in case of an initially fatal appearing prognosis. In selected cases, extracorporeal support can generate enough time for diagnosis and therapy. However, transparent planning, including discussion of best supportive care strategies involving the patient's family are indispensable requirements for starting ECMO in such patients.

Influence of immunosuppression in patients with severe acute respiratory distress syndrome on veno-venous extracorporeal membrane oxygenation therapy.

Prognosis of patients suffering from acute respiratory distress syndrome (ARDS) is poor. This is especially true for immunosuppressed patients. It is controverisal whether these patients should receive veno-venous extracorporeal membrane oxygenation (VV ECMO) while evidence on this topic is sparse. We report retrospective data of a single-center registry of patients with severe ARDS requiring ECMO support between October 2010 and June 2019. Patients were analyzed by their status of immunosuppression. ECMO weaning success and hospital survival were analyzed before and after propensity score matching (PSM). Moreover, ventilator free days (VFD) were compared. A total of 288 patients were analyzed (age 55 years, 67% male), 88 (31%) presented with immunosuppression. Survival rates were lower in immunosuppressed patients (27% vs. 53%, P < .001 and 27% vs. 48% after PSM, P = .006). VFD (60 days) were lower for patients with immunosuppression (11.9 vs. 22.4, P < .001), and immunosuppression was an independent predictor for mortality in multivariate analysis. Hospital survival was 20%, 14%, 35%, and 46% for patients with oncological malignancies, solid organ transplantation, autoimmune diseases, and HIV, respectively. In this analysis immunosuppression was an independent predictor for mortality. However, there were major differences in the weaning and survival rates between the etiologies of immunosuppression which should be considered in decision making.

Intensive Care Resources and 60-Day Survival of Critically-Ill COVID-19 Patients.

BACKGROUND: Germany reported sufficient intensive care unit (ICU) resources throughout the first wave of coronavirus disease 2019 (COVID-19). The treatment of critically ill COVID-19 patients without rationing may improve the outcome. We therefore analyzed ICU resources allocated to COVID-19 patients with respiratory failure and their outcomes. METHODS: Retrospectively, we enrolled severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) polymerase chain reaction (PCR)-positive patients with respiratory failure from 03/08/2020 to 04/08/2020 and followed until 05/28/2020 in the university hospital of Freiburg, Germany. RESULTS: In the defined interval, 34 COVID-19 patients were admitted to the ICU with median age of 67±13 (31-86) years. Six of 34 (17.6%) were female. All patients suffered from moderate or severe acute respiratory distress syndrome (ARDS), 91.2% of the patients were intubated and 23.5% required extracorporeal membrane oxygenation (ECMO). Proning was performed in 67.6%, renal replacement therapy (RRT) was required in 35.3%. Ninety-six percent required more than 20 nursing hours per day. Mean ICU stay was 21±19 (1-81) days. Sixty-day survival of critically ill COVID-19 patients was 50.0% (17/34). Causes of death were multi-organ failure (52.9%), refractory ARDS (17.6%) and intracerebral hemorrhage (17.6%). CONCLUSIONS: Treatment of critically ill COVID-19 patients is protracted and resource-intense. In a context without resources shortage, 50% of COVID-19 with respiratory failure survived up to 60 days.