Prevalence and Risk Factors for Weaning Failure From Venovenous Extracorporeal Membrane Oxygenation in Patients With Severe Acute Respiratory Insufficiency.

OBJECTIVE: Analysis of the prevalence and risk factors for weaning failure from venovenous extracorporeal membrane oxygenation (VV-ECMO) in patients with severe acute respiratory insufficiency. DESIGN: Single-center retrospective observational study. SETTING: Sixteen beds medical ICU at the University Hospital Regensburg. PATIENTS: Two hundred twenty-seven patients with severe acute respiratory insufficiency requiring VV-ECMO support between October 2011 and December 2017. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Patients meeting our ECMO weaning criteria (Sp o2 ≥ 90% with F io2 ≤ 0.4 or Pa o2 /F io2 > 150 mm Hg, pH = 7.35-7.45, positive end-expiratory pressure ≤ 10 cm H 2 O, driving pressure < 15 cm H 2 O, respiratory rate < 30/min, tidal volume > 5 mL/kg, ECMO bloodflow ≈ 1. 5 L/min, sweep gas flow ≈ 1 L/min, heart rate < 120/min, systolic blood pressure 90-160 mm Hg, norepinephrine < 0.2 µg/[kg*min]) underwent an ECMO weaning trial (EWT) with pausing sweep gas flow. Arterial blood gas analysis, respiratory and ventilator parameters were recorded prior, during, and after EWTs. Baseline data, including demographics, vitals, respiratory, ventilator, and laboratory parameters were recorded at the time of cannulation. One hundred seventy-nine of 227 (79%) patients were successfully decannulated. Ten patients (4%) underwent prolonged weaning of at least three failed EWTs before successful decannulation. The respiratory rate (19/min vs 16/min, p = 0.002) and Pa co2 (44 mm Hg vs 40 mm Hg, p = 0.003) were higher before failed than successful EWTs. Both parameters were risk factors for ECMO weaning failure (Pa co2 : odds ratio [OR] 1.05; 95% CI, 1.001-1.10; p = 0.045; respiratory rate: OR 1.10; 95% CI, 1.04-1.15; p < 0.001) in multivariable analysis. The rapid shallow breathing index [42 (1/L*min), vs 35 (1/L*min), p = 0.052) was higher before failed than successful EWTs. The decline of Sa o2 and Pa o2 /F io2 during EWTs was higher in failed than successful trials. CONCLUSIONS: Seventy-nine percent of patients were successfully decannulated with only 4% needing prolonged ECMO weaning. Before EWT only parameters of impaired ventilation (insufficient decarboxylation, higher respiratory rate) but not of oxygenation were predictive for weaning failure, whereas during EWT-impaired oxygenation was associated with weaning failure.

Bilateral Femoral Cannulation Is Associated With Reduced Severe Limb Ischemia-Related Complications Compared With Unilateral Femoral Cannulation in Adult Peripheral Venoarterial Extracorporeal Membrane Oxygenation: Results From the Extracorporeal Life Support Registry.

OBJECTIVES: Peripheral venoarterial extracorporeal membrane oxygenation (ECMO) with femoral access is obtained through unilateral or bilateral groin cannulation. Whether one cannulation strategy is associated with a lower risk for limb ischemia remains unknown. We aim to assess if one strategy is preferable. DESIGN: A retrospective cohort study based on the Extracorporeal Life Support Organization registry. SETTING: ECMO centers worldwide included in the Extracorporeal Life Support Organization registry. PATIENTS: All adult patients (≥ 18 yr) who received peripheral venoarterial ECMO with femoral access and were included from 2014 to 2020. INTERVENTIONS: Unilateral or bilateral femoral cannulation. MEASUREMENTS AND MAIN RESULTS: The primary outcome was the occurrence of limb ischemia defined as a composite endpoint including the need for a distal perfusion cannula (DPC) after 6 hours from implantation, compartment syndrome/fasciotomy, amputation, revascularization, and thrombectomy. Secondary endpoints included bleeding at the peripheral cannulation site, need for vessel repair, vessel repair after decannulation, and in-hospital death. Propensity score matching was performed to account for confounders. Overall, 19,093 patients underwent peripheral venoarterial ECMO through unilateral ( n = 11,965) or bilateral ( n = 7,128) femoral cannulation. Limb ischemia requiring any intervention was not different between both groups (bilateral vs unilateral: odds ratio [OR], 0.92; 95% CI, 0.82-1.02). However, there was a lower rate of compartment syndrome/fasciotomy in the bilateral group (bilateral vs unilateral: OR, 0.80; 95% CI, 0.66-0.97). Bilateral cannulation was also associated with lower odds of cannulation site bleeding (bilateral vs unilateral: OR, 0.87; 95% CI, 0.76-0.99), vessel repair (bilateral vs unilateral: OR, 0.55; 95% CI, 0.38-0.79), and in-hospital mortality (bilateral vs unilateral: OR, 0.85; 95% CI, 0.81-0.91) compared with unilateral cannulation. These findings were unchanged after propensity matching. CONCLUSIONS: This study showed no risk reduction for overall limb ischemia-related events requiring DPC after 6 hours when comparing bilateral to unilateral femoral cannulation in peripheral venoarterial ECMO. However, bilateral cannulation was associated with a reduced risk for compartment syndrome/fasciotomy, lower rates of bleeding and vessel repair during ECMO, and lower in-hospital mortality.

Postpartum cryptococcosis in an HIV-negative patient.

PURPOSE AND METHODS: We present an unusual case of an HIV-negative patient with postpartum pulmonary cryptococcosis and cryptococcemia. RESULTS: The diagnostic methods and treatment of cryptococcosis in a postpartum patient are presented in this case report. Due to anaphylaxis to liposomal amphotericin B, desensitisation to the drug was performed. CONCLUSION: We would like to raise awareness about rare infections such as cryptococcosis in pregnancy and the postpartum period. In addition, we were able to document a successful desensitisation to liposomal amphotericin B.

Negative impact of face masks in patients with interstitial lung disease: A prospective study.

INTRODUCTION: Face masks increase airway resistance, data on the actual extent of this effect are scarce. The aim of this study was to assess the effect of different mask types on clinical parameters during moderate exercise in healthy non-smokers, active smokers and patients with interstitial lung disease (ILD) without the need of oxygen therapy. METHODS: In a prospective observational pilot study participants performed a six-minute walk test without mask, with a surgical mask, a well-fitted FFP2 mask and with a valved FFP3 mask. Respiratory rate, blood pressure, heart rate, blood gas analysis parameters, dyspnoea and six-minute walk distance were measured. Data were analysed in an ANOVA model. RESULTS: 21 healthy participants, 17 active smokers without known pulmonary disease and 15 patients with interstitial lung disease were included. Participants with ILD had a significant lower walking distance, a higher respiratory rate and a lower pO2 when using FFP2 masks, but not with valved FFP3 masks or surgical masks compared to not wearing a mask. CONCLUSION: For patients with ILD without the need of oxygen therapy wearing an FFP2 mask had a negative impact on pO2, respiratory rate and walking distance in the six-minute walk test. This effect was not seen with valved FFP3 masks or surgical masks.

Short report: impact of selective reporting of antibiotic susceptibility testing on antibiotic use in patients with bloodstream infection with Enterococcus faecalis.

INTRODUCTION: Bloodstream infections with Enterococcus faecalis are associated with relevant morbidity and mortality. Targeted antimicrobial therapy is essential. The choice of an adequate treatment may be challenging when susceptibility testing offers different options. Selective reporting of antibiotic susceptibility test results might lead to a more tailored antibiotic therapy and could therefore be an important antimicrobial stewardship program intervention. The aim of this study was to analyse whether the introduction of selective reporting of antibiotic test results leads to a more targeted antibiotic therapy in patients with bloodstream infection with Enterococcus faecalis. METHODS: This study was performed as a retrospective cohort study at the University Hospital Regensburg, Germany. All patients with blood cultures positive for Enterococcus faecalis between March 2003 and March 2022 were analysed. In February 2014 selective reporting of antibiotic susceptibility test results omitting sensitivity results for agents not recommended was introduced. RESULTS: 263 patients with blood cultures positive for Enterococcus faecalis were included. After introduction of selective reporting of antibiotic tests (AI) significantly more patients received ampicillin than before introduction of selective reporting (BI) (9.6% BI vs. 34.6% AI, p < 0.001). CONCLUSION: Selective reporting of antibiotic susceptibility test results led to a significantly higher use of ampicillin.

The effects of nitric oxide on coagulation and inflammation in ex vivo models of extracorporeal membrane oxygenation and cardiopulmonary bypass.

BACKGROUND: Extracorporeal life support (ECLS) has extensive applications in managing patients with acute cardiac and pulmonary failure. Two primary modalities of ECLS, cardiopulmonary bypass (CPB) and extracorporeal membrane oxygenation (ECMO), include several similarities in their composition, complications, and patient outcomes. Both CPB and ECMO pose a high risk of thrombus formation and platelet activation due to the large surface area of the devices and bleeding due to system anticoagulation. Therefore, novel methods of anticoagulation are needed to reduce the morbidity and mortality associated with extracorporeal support. Nitric oxide (NO) has potent antiplatelet properties and presents a promising alternative or addition to anticoagulation with heparin during extracorporeal support. METHODS: We developed two ex vivo models of CPB and ECMO to investigate NO effects on anticoagulation and inflammation in these systems. RESULTS: Sole addition of NO as an anticoagulant was not successful in preventing thrombus formation in the ex vivo setups, therefore a combination of low-level heparin with NO was used. Antiplatelet effects were observed in the ex vivo ECMO model when NO was delivered at 80 ppm. Platelet count was preserved after 480 min when NO was delivered at 30 ppm. CONCLUSION: Combined delivery of NO and heparin did not improve haemocompatibility in either ex vivo model of CPB and ECMO. Anti-inflammatory effects of NO in ECMO systems have to be evaluated further.

Randomized Clinical Study of Temporary Transvenous Phrenic Nerve Stimulation in Difficult-to-Wean Patients.

Rationale: Diaphragm dysfunction is frequently observed in critically ill patients with difficult weaning from mechanical ventilation. Objectives: To evaluate the effects of temporary transvenous diaphragm neurostimulation on weaning outcome and maximal inspiratory pressure. Methods: Multicenter, open-label, randomized, controlled study. Patients aged ⩾18 years on invasive mechanical ventilation for ⩾4 days and having failed at least two weaning attempts received temporary transvenous diaphragm neurostimulation using a multielectrode stimulating central venous catheter (bilateral phrenic stimulation) and standard of care (treatment) (n = 57) or standard of care (control) (n = 55). In seven patients, the catheter could not be inserted, and in seven others, pacing therapy could not be delivered; consequently, data were available for 43 patients. The primary outcome was the proportion of patients successfully weaned. Other endpoints were mechanical ventilation duration, 30-day survival, maximal inspiratory pressure, diaphragm-thickening fraction, adverse events, and stimulation-related pain. Measurements and Main Results: The incidences of successful weaning were 82% (treatment) and 74% (control) (absolute difference [95% confidence interval (CI)], 7% [-10 to 25]), P = 0.59. Mechanical ventilation duration (mean ± SD) was 12.7 ± 9.9 days and 14.1 ± 10.8 days, respectively, P = 0.50; maximal inspiratory pressure increased by 16.6 cm H2O and 4.8 cm H2O, respectively (difference [95% CI], 11.8 [5 to 19]), P = 0.001; and right hemidiaphragm thickening fraction during unassisted spontaneous breathing was +17% and -14%, respectively, P = 0.006, without correlation with changes in maximal inspiratory pressure. Serious adverse event frequency was similar in both groups. Median stimulation-related pain in the treatment group was 0 (no pain). Conclusions: Temporary transvenous diaphragm neurostimulation did not increase the proportion of successful weaning from mechanical ventilation. It was associated with a significant increase in maximal inspiratory pressure, suggesting reversal of the course of diaphragm dysfunction. Clinical trial registered with www.clinicaltrials.gov (NCT03096639) and the European Database on Medical Devices (CIV-17-06-020004).

Piloting an ICU follow-up clinic to improve health-related quality of life in ICU survivors after a prolonged intensive care stay (PINA): feasibility of a pragmatic randomised controlled trial.

BACKGROUND: ICU survivors often suffer from prolonged physical and mental impairments resulting in the so called "Post-Intensive Care Syndrome" (PICS). The aftercare of former ICU patients affected by PICS in particular has not been addressed sufficiently in Germany so far. The aim of this study was to evaluate the feasibility of a pragmatic randomised trial (RCT) comparing an intensive care unit (ICU) follow-up clinic intervention to usual care. METHODS: This pilot study in a German university hospital evaluated the feasibility of a pragmatic RCT. Patients were assigned in a 1:1 ratio to an ICU follow-up clinic intervention or to usual care. The concept of this follow-up clinic was previously developed in a participatory process with patients, next of kin, health care professionals and researchers. We performed a process evaluation and determined acceptability, fidelity, completeness of measurement instruments and practicality as feasibility outcomes. The RCT's primary outcome (health-related quality of life) was assessed six months after ICU discharge by means of the physical component scale of the Short-Form-12 self-report questionnaire. RESULTS: The pilot study was conducted from June 2020 to May 2021 with 21 and 20 participants in the intervention and control group. Principal findings related to feasibility were 85% consent rate (N = 48), 62% fidelity rate, 34% attrition rate (N = 41) and 77% completeness of outcome measurements. The primary effectiveness outcome (health-related quality of life) could be measured in 93% of participants who completed the study (N = 27). The majority of participants (85%) needed assistance with follow-up questionnaires (practicality). Median length of ICU stay was 13 days and 85% (N = 41) received mechanical ventilation, median Sequential Organ Failure Assessment Score was nine. Six-month follow-up assessment was planned for all study participants and performed for 66% (N = 41) of the participants after 197 days (median). CONCLUSION: The participatory developed intervention of an ICU follow-up clinic and the pragmatic pilot RCT both seem to be feasible. We recommend to start a pragmatic RCT on the effectiveness of the ICU follow-up clinic. TRIAL REGISTRATION: ClinicalTrials.gov US NLM, NCT04186468, Submission: 02/12/2019, Registration: 04/12/2019, https://clinicaltrials.gov/ct2/show/NCT04186468.

Intracranial hemorrhage in a large cohort of patients supported with veno-venous ECMO. A retrospective single-center analysis.

BACKGROUND: Intracranial bleeding (ICB) is a serious complication during veno-venous extracorporeal membrane oxygenation (V-V ECMO), with potentially fatal consequences. PURPOSE: This study aimed to evaluate the incidence, time of detection of ICB among patients treated with V-V ECMO and potential risk factors for developing ICB during V-V ECMO. METHODS: Five hundred fifty six patients were included in this retrospective single center analysis. RESULTS: Median time on V-V ECMO was 9 (IQR 6-15) days. Intracranial bleeding during V-V ECMO was detected in 10.9% of all patients (61 patients with ICB). Only 17 patients with ICB presented obvious clinical symptoms. Intracranial bleeding was detected on cerebral imaging in median after 5 days (IQR 1-14) after starting V-V ECMO. Overall survival to hospital discharge was 63.7% (ICB: 29.5%). Risk factors of ICB before starting V-V ECMO in univariable analysis were platelets <100/nl (OR: 3.82), creatinine >1.5mg/dl (OR: 1.98), norepinephrine >2.5mg/h (OR: 2.5), ASAT >80U/L (OR: 1.86), blood-urea >100mg/dl (OR: 1.81) and LDH >550u/L (OR: 2.07). Factors associated with cannulation were rapid decrease in paCO2 >35mmHg (OR: 2.56) and rapid decrease in norepinephrine >1mg/h (OR: 2.53). Multivariable analysis revealed low platelets, high paCO2 before ECMO, and rapid drop in paCO2 after V-V ECMO initiation as significant risk factors for ICB. CONCLUSION: The results emphasize that ICB is a frequent complication during V-V ECMO. Many bleedings were incidental findings, therefore screening for ICB is advisable. The univariate risk factors reflect the underlying disease severity, coagulation disorders and peri-cannulation factors, and may help to identify patients at risk.

Evaluation of a new magnetically suspended centrifugal neonatal pump in healthy animals using a veno-venous extracorporeal membrane oxygenation configuration.

BACKGROUND: The objective of this animal study was to evaluate the hemodynamic performance of a new centrifugal pump for extra-corporeal membrane oxygenation (ECMO) support in neonates. METHODS: Six healthy swines were supported with veno-venous ECMO with the New Born ECMOLife centrifugal pump (Eurosets, Medolla, Italy) at different flow rates: 0.25, 0.5, 0.6, and 0.8 L/min; three animals were evaluated at low-flows (0.25 and 0.5 L/min) and three at high-flows (0.6 and 0.8 L/min). Each flow was maintained for 4 hours. Blood samples were collected at different time-points. Hematological and biochemical parameters and ECMO parameters [flow, revolutions per minute (RPM), drainage pressure, and the oxygenator pressure drop] were evaluated. RESULTS: The increase of the pump flow from 0.25 to 0.5 L/min or from 0.6 to 0.8 L/min required significantly higher RPM and produced significantly higher pump pressures [from 0.25 to 0.5 L/min: 1470 (1253-1569) versus 2652 (2589-2750) RPM and 40 (26-57) versus 125 (113-139) mmHg, respectively; p < .0001 for both - from 0.60 to 0.8 L/min: 1950 (1901-2271) versus 2428 (2400-2518) RPM and 66 (62-86) versus 106 (101-113) mmHg, respectively; p < .0001 for both]. Median drainage pressure significantly decreased from -18 (-22; -16) mmHg to -55 (-63; -48) mmHg when the pump flow was increased from 0.25 to 0.5 L/min (p < .0001). When pump flow increased from 0.6 to 0.8 L/min, drainage pressure decreased from -32 (-39; -24) mmHg to -50 (-52; -43) mmHg, (p < .0001). Compared to pre-ECMO values, the median levels of lactate dehydrogenase, d-dimer, hematocrit, and platelet count decreased after ECMO start at all flow rates, probably due to hemodilution. Plasma-free hemoglobin, instead, showed a modest increase compared to pre-ECMO values during all experiments at different pump flow rates. However, these changes were not clinically relevant. CONCLUSIONS: In this animal study, the "New Born ECMOLife" centrifugal pump showed good hemodynamic performance. Long-term studies are needed to evaluate biocompatibility of this new ECMO pump.

[Aftercare of ICU patients: A task for pneumology?] / Intensivnachsorge-Ambulanz ­ Nachsorge kritisch kranker Patienten ­ Eine Aufgabe für die Pneumologie?

As the number of patients treated in intensive care medicine increases, so does the number of those who suffer from the long-term consequences of critical illness and the consequences of a stay in an intensive care unit. For this group of patients with a post-intensive care syndrome (PICS), there are currently no specialized outpatient care structures that follow the hospital stay and possible follow-up treatment. A number of studies are researching the effectiveness of intensive care outpatient clinics nationally and internationally.After presenting the PICS and the associated complex need for care, this review article presents various model projects for outpatient follow-up care of critically ill patients. We discuss whether the field of pneumology is particularly suitable for the study of therapy control of complex clinical pictures since it has vast experience in the treatment of intensive care patients and the outpatient care of chronically ill patients.

Defining and understanding the "extra-corporeal membrane oxygenation gap" in the veno-venous configuration: Timing and causes of death.

In-hospital mortality of adult veno-venous extracorporeal membrane oxygenation (V-V ECMO) patients remains invariably high. However, little is known regarding timing and causes of in-hospital death, either on-ECMO or after weaning. The current review aims to investigate the timing and causes of death of adult patients during hospital admittance for V-V ECMO, and to define the V-V ECMO gap, which is represented by the patients that are successfully weaned of ECMO but still die during hospital stay. A systematic search was performed using electronic MEDLINE and EMBASE databases through PubMed. Studies reporting on adult V-V ECMO patients from January 2006 to December 2020 were screened. Studies that did not report on at least on-ECMO mortality and discharge rate were excluded from analysis as they could not provide the required information regarding the proposed V-V ECMO-gap. Mortality rates on-ECMO and after weaning, as well as weaning and discharge rates, were analyzed as primary outcomes. Secondary outcomes were the causes of death and complications. Initially, 35 studies were finally included in this review. Merely 24 of these studies (comprising 975 patients) reported on prespecified V-V ECMO outcomes (on-ECMO mortality and discharge rate). Mortality on V-V ECMO support was 27.8% (95% confidence interval (CI) 22.5%-33.2%), whereas mortality after successful weaning was 12.7% (95% CI 8.8%-16.6%, defining the V-V ECMO gap). 72.2% of patients (95% CI 66.8%-77.5%) were weaned successfully from support and 56.8% (95% CI 49.9%-63.8%) of patients were discharged from hospital. The most common causes of death on ECMO were multiple organ failure, bleeding, and sepsis. Most common causes of death after weaning were multiorgan failure and sepsis. Although the majority of patients are weaned successfully from V-V ECMO support, a significant proportion of subjects still die during hospital stay, defining the V-V ECMO gap. Overall, timing and causes of death are poorly reported in current literature. Future studies on V-V ECMO should describe morbidity and mortality outcomes in more detail in relation to the timing of the events, to improve patient management, due to enhanced understanding of the clinical course.

Argatroban versus heparin in patients without heparin-induced thrombocytopenia during venovenous extracorporeal membrane oxygenation: a propensity-score matched study.

BACKGROUND: During venovenous extracorporeal membrane oxygenation (vvECMO), direct thrombin inhibitors are considered by some potentially advantageous over unfractionated heparin (UFH). We tested the hypothesis that Argatroban is non-inferior to UFH regarding thrombosis and bleeding during vvECMO. METHODS: We conducted a propensity-score matched observational non-inferiority study of consecutive patients without heparin-induced-thrombocytopenia (HIT) on vvECMO, treated between January 2006 and March 2019 in the medical intensive care unit at the University Hospital Regensburg. Anticoagulation was realized with UFH until August 2017 and with Argatroban from September 2017 onwards. Target activated partial thromboplastin time was 50 ± 5seconds in both groups. Primary composite endpoint was major thrombosis and/or major bleeding. Major bleeding was defined as a drop in hemoglobin of ≥ 2 g/dl/day or in transfusion of ≥ 2 packed red cells/24 h, or retroperitoneal, cerebral, or pulmonary bleeding. Major thrombosis was defined as obstruction of > 50% of the vessel lumen diameter by means of duplex sonography. We also assessed technical complications such as oxygenator defects or pump head thrombosis, the time-course of platelets, and the cost of anticoagulation (including HIT-testing). RESULTS: Out of 465 patients receiving UFH, 78 were matched to 39 patients receiving Argatroban. The primary endpoint occurred in 79% of patients in the Argatroban group and in 83% in the UFH group (non-inferiority for Argatroban, p = 0.026). The occurrence of technical complications was equally distributed (Argatroban 49% vs. UFH 42%, p = 0.511). The number of platelets was similar in both groups before ECMO therapy but lower in the UFH group after end of ECMO support (median [IQR]: 141 [104;198]/nl vs. 107 [54;171]/nl, p = 0.010). Anticoagulation costs per day of ECMO were higher in the Argatroban group (€26 [13.8;53.0] vs. €0.9 [0.5;1.5], p < 0.001) but not after accounting for blood products and HIT-testing (€63 [42;171) vs. €40 [17;158], p = 0.074). CONCLUSION: In patients without HIT on vvECMO, Argatroban was non-inferior to UFH regarding bleeding and thrombosis. The occurrence of technical complications was similarly distributed. Argatroban may have less impact on platelet decrease during ECMO, but this finding needs further evaluation. Direct drug costs were higher for Argatroban but comparable to UFH after accounting for HIT-testing and transfusions.

Assessing potential for aortoiliac vascular injury from venoarterial extracorporeal membrane oxygenation cannulae: An in vitro particle image velocimetry study.

Limb ischemia is a major complication associated with peripheral venoarterial extracorporeal membrane oxygenation (VA-ECMO). The high velocity jet from arterial cannulae can cause "sandblasting" injuries to the arterial endothelium, with the potential risk of distal embolization and end organ damage. The aim of this study was to identify, for a range of clinically relevant VA-ECMO cannulae and flow rates, any regions of peak flow velocity on the aortic wall which may predispose to vascular injury, and any regions of low-velocity flow which may predispose to thrombus formation. A silicone model of the aortic and iliac vessels was sourced and the right external iliac artery was cannulated. Cannulae ranged from 15 to 21 Fr in size. Simulated steady state ECMO flow rates were instituted using a magnetically levitated pump (CentriMag pump). Adaptive particle image velocimetry was performed for each cannula at 3, 3.5, 4, and 4.5 L/min. For all cannulae, in both horizontal and vertical side hole orientations, the peak velocity on the aortic wall ranged from 0.3 to 0.45 m/s, and the regions of lowest velocity flow were 0.05 m/s. The magnitude of peak velocity flow on the aortic wall was not different between a single pair versus multiple pairs of side holes. Maximum velocity flow on the aortic wall occurred earlier at a lower pump flow rate in the vertical orientation of distal side holes compared to a horizontal position. The presence of multiple paired side holes was associated with fewer low-velocity flow regions, and some retrograde flow, in the distal abdominal aorta compared to cannulae with a single pair of side holes. From this in vitro visualization study, the selection of a cannula design with multiple versus single pairs of side holes did not change the magnitude of peak velocity flow delivered to the vessel wall. Cannulae with multiple side holes were associated with fewer regions of low-velocity flow in the distal abdominal aorta. Further in vivo studies, and ideally clinical data would be required to assess any correlation of peak velocity flows with incidence of vascular injury, and any low-velocity flow regions with incidence of thrombosis.

Understanding the "extracorporeal membrane oxygenation gap" in veno-arterial configuration for adult patients: Timing and causes of death.

Timing and causes of hospital mortality in adult patients undergoing veno-arterial extracorporeal membrane oxygenation (V-A ECMO) have been poorly described. Aim of the current review was to investigate the timing and causes of death of adult patients supported with V-A ECMO and subsequently define the "V-A ECMO gap," which represents the patients who are successfully weaned of ECMO but eventually die during hospital stay. A systematic search was performed using electronic MEDLINE and EMBASE databases through PubMed. Studies reporting on adult V-A ECMO patients from January 1993 to December 2020 were screened. The studies included in this review were studies that reported more than 10 adult, human patients, and no mechanical circulatory support other than V-A ECMO. Information extracted from each study included mainly mortality and causes of death on ECMO and after weaning. Complications and discharge rates were also extracted. Sixty studies with 9181 patients were included for analysis in this systematic review. Overall mortality was 38.0% (95% confidence intervals [CIs] 34.2%-41.9%) during V-A ECMO support (reported by 60 studies) and 15.3% (95% CI 11.1%-19.5%, reported by 57 studies) after weaning. Finally, 44.0% of patients (95% CI 39.8-52.2) were discharged from hospital (reported by 60 studies). Most common causes of death on ECMO were multiple organ failure, followed by cardiac failure and neurological causes. More than one-third of V-A ECMO patients die during ECMO support. Additionally, many of successfully weaned patients still decease during hospital stay, defining the "V-A ECMO gap." Underreporting and lack of uniformity in reporting of important parameters remains problematic in ECMO research. Future studies should uniformly define timing and causes of death in V-A ECMO patients to better understand the effectiveness and complications of this support.

Adaptive servo-ventilation in patients with chronic heart failure and sleep disordered breathing: predictors of usage.

PURPOSE: Adaptive servo-ventilation (ASV) is a therapy designed for patients with central sleep apnea (CSA) and Cheyne Stokes respiration. The aim of this study was to find predictors of ASV usage in patients with CSA in a routine sleep clinic cohort. METHODS: In this retrospective study, consecutive patients in whom ASV therapy was initiated at the University Hospital Regensburg between 2011 and 2015, were analyzed. Analysis included polysomnographies of diagnostic and ASV initiation nights, a phone questionnaire on ASV usage, readout of the ASV device 1 month after initiation ("early ASV usage," 1 month after ASV initiation), and the readout of the last month before a reappointment date set in 2015 ("late ASV usage," median 17 months after ASV initiation). RESULTS: In 69 consecutive patients, the mean early and late ASV usage per night was 4.8 ± 2.5 h and 4.1 ± 3.0 h, respectively. Seventeen months after initiation, 57% of patients used the device ≥ 4 h per night, and of those 91% reported a subjective benefit from ASV therapy. Early ASV usage was significantly associated with late ASV usage (univariable regression: Beta 0.8, 95%CI [0.6; 1.0] p < 0.001). In multivariable regression analysis, short duration of slow wave sleep (N3) during diagnostic polysomnography (Beta - 6.2, 95%CI [- 11.0; - 1.5]; p = 0.011) and subjective benefit from ASV (Beta 174.0, 95%CI [68.6; 279.5]; p = 0.002) were significantly associated with longer late ASV usage. CONCLUSION: Early ASV usage predicts late ASV usage. In addition, low slow wave sleep before ASV initiation and subjective benefit from ASV may contribute to higher late ASV usage.

ECMO in COVID-19-prolonged therapy needed? A retrospective analysis of outcome and prognostic factors.

BACKGROUND: The role of venovenous extracorporeal membrane oxygenation (VV ECMO) in patients with COVID-19-induced acute respiratory distress syndrome (ARDS) still remains unclear. Our aim was to investigate the clinical course and outcome of those patients and to identify factors associated with the need for prolonged ECMO therapy. METHODS: A retrospective single-center study on patients with VV ECMO for COVID-19-associated ARDS was performed. Baseline characteristics, ventilatory and ECMO parameters, and laboratory and virological results were evaluated over time. Six months follow-up was assessed. RESULTS: Eleven of 16 patients (68.8%) survived to 6 months follow-up with four patients requiring short-term (<28 days) and seven requiring prolonged (⩾28 days) ECMO support. Lung compliance before ECMO was higher in the prolonged than in the short-term group (28.1 (28.8-32.1) ml/cmH2O vs 18.7 (17.7-25.0) ml/cmH2O, p = 0.030). Mechanical ventilation before ECMO was longer (19 (16-23) days vs 5 (5-9) days, p = 0.002) and SOFA score was higher (12.0 (10.5-17.0) vs 10.0 (9.0-10.0), p = 0.002) in non-survivors compared to survivors. Low viral load during the first days on ECMO tended to indicate worse outcomes. Seroconversion against SARS-CoV-2 occurred in all patients, but did not affect outcome. CONCLUSIONS: VV ECMO support for COVID-19-induced ARDS is justified if initiated early and at an experienced ECMO center. Prolonged ECMO therapy might be required in those patients. Although no relevant predictive factors for the duration of ECMO support were found, the decision to stop therapy should not be made dependent of the length of ECMO treatment.

The effect of hyperoxia on inflammation and platelet responses in an ex vivo extracorporeal membrane oxygenation circuit.

Use of extracorporeal membrane oxygenation (ECMO) is expanding, however, it is still associated with significant morbidity and mortality. Activation of inflammatory and innate immune responses and hemostatic alterations contribute to complications. Hyperoxia may play a role in exacerbating these responses. Nine ex vivo ECMO circuits were tested using fresh healthy human whole blood, with two oxygen levels: 21% inspired fraction of oxygen (FiO2 ; mild hyperoxia; n = 5) and 100% FiO2 (severe hyperoxia; n = 4). Serial blood samples were taken for analysis of platelet aggregometry, leukocyte activation, inflammatory, and oxidative stress markers. ECMO resulted in reduced adenosine diphosphate- (P < .05) and thrombin receptor activating peptide-induced (P < .05) platelet aggregation, as well as increasing levels of the neutrophil activation marker, neutrophil elastase (P = .013). Additionally, levels of the inflammatory chemokine interleukin-8 were elevated (P < .05) and the activity of superoxide dismutase, a marker of oxidative stress, was increased (P = .002). Hyperoxia did not augment these responses, with no significant differences detected between mild and severe hyperoxia. Our ex vivo model of ECMO revealed that the circuit itself triggers a pro-inflammatory and oxidative stress response, however, exposure to supra-physiologic oxygen does not amplify that response. Extended-duration studies and inclusion of an endothelial component could be beneficial in characterizing longer term changes.

Incidence of early intra-cranial bleeding and ischaemia in adult veno-arterial extracorporeal membrane oxygenation and extracorporeal cardiopulmonary resuscitation patients: a retrospective analysis of risk factors.

BACKGROUND: Cerebral complications in veno-arterial extracorporeal membrane oxygenation are known to have a strong impact on mortality and morbidity. Aim of this study is to investigate the early incidence, risk factors and in-hospital mortality of intra-cranial ischaemia and haemorrhage in adults undergoing veno-arterial extracorporeal membrane oxygenation treatment. METHODS: This study is a single-centre retrospective analysis on adult patients undergoing veno-arterial extracorporeal membrane oxygenation for different indications. The inclusion criterion included patients with early routine cerebral computed tomography imaging during extracorporeal membrane oxygenation, with no clinical evidence of cerebral pathology prior to cannulation. Cerebral complications were grouped by aetiology and the territories of the brain's supplying arteries. RESULTS: One hundred eighty-seven adult patients with a total of 190 veno-arterial extracorporeal membrane oxygenation treatments were included. A total of 16.3% (n = 31) had evidence of either cerebral ischaemia (11.1%) or haemorrhage (5.8%); one patient suffered from both. Cerebral computed tomography scans were performed early in median on the first day after extracorporeal membrane oxygenation cannulation; in-hospital mortality of intra-cranial ischaemia and haemorrhage was 71.4% and 45.5%, respectively. Associated with an increased risk for ischaemic lesions were cannulation of the ascending aorta, higher age, presence of an autoimmune disease and cardiac surgery prior to veno-arterial extracorporeal membrane oxygenation. An association with haemorrhagic lesions was found for a lower blood PaCO2 at 2 hours, lower blood flow through the extracorporeal membrane oxygenation device at 2 hours, higher international normalized ratio and constantly higher activated partial thromboplastin time values as well as higher mean arterial pressures until haemorrhagic lesions were evident. CONCLUSION: Cerebral complications are frequent in patients on veno-arterial extracorporeal membrane oxygenation and may be clinically silent events. Careful monitoring with routine neuroimaging seems to be the most appropriate diagnostic approach at present. Intra-cranial ischaemia occurs more frequent than haemorrhage and is associated with cannulation of the aorta ascendens.

Ex vivo models for research in extracorporeal membrane oxygenation: a systematic review of the literature.

With ongoing progress of components of extracorporeal membrane oxygenation including improvements of oxygenators, pumps, and coating materials, extracorporeal membrane oxygenation became increasingly accepted in the clinical practice. A suitable testing in an adequate setup is essential for the development of new technical aspects. Relevant tests can be conducted in ex vivo models specifically designed to test certain aspects. Different setups have been used in the past for specific research questions. We conducted a systematic literature review of ex vivo models of extracorporeal membrane oxygenation components. MEDLINE and Embase were searched between January 1996 and October 2017. The inclusion criteria were ex vivo models including features of extracorporeal membrane oxygenation technology. The exclusion criteria were clinical studies, abstracts, studies in which the model of extracorporeal membrane oxygenation has been reported previously, and studies not reporting on extracorporeal membrane oxygenation components. A total of 50 studies reporting on different ex vivo extracorporeal membrane oxygenation models have been identified from the literature search. Models have been grouped according to the specific research question they were designed to test for. The groups are focused on oxygenator performance, pump performance, hemostasis, and pharmacokinetics. Pre-clinical testing including use of ex vivo models is an important step in the development and improvement of extracorporeal membrane oxygenation components and materials. Furthermore, ex vivo models offer valuable insights for clinicians to better understand the consequences of choice of components, setup, and management of an extracorporeal membrane oxygenation circuit in any given condition. There is a need to standardize the reporting of pre-clinical studies in this area and to develop best practice in their design.