[Pathophysiology of Acute Respiratory Distress Syndrome]. / Pathophysiologie des akuten Lungenversagens (ARDS).

Acute respiratory distress syndrome (ARDS) is a common condition in intensive care medicine. Various intra- and extrapulmonal causes may trigger an epithelial and endothelial permeability increase, which leads to impaired gas exchange due to fluid overload of the alveoli and transmigration of leukocytes. This results in hypoxemia and hypercapnia, as well as deleterious consequences for the macro- and microcirculation with the risk of multi-organ failure and high mortality. This review summarizes ARDS pathophysiology and clinical consequences.

International survey of neuromonitoring and neurodevelopmental outcome in children and adults supported on extracorporeal membrane oxygenation in Europe.

BACKGROUND: Adverse neurological events during extracorporeal membrane oxygenation (ECMO) are common and may be associated with devastating consequences. Close monitoring, early identification and prompt intervention can mitigate early and late neurological morbidity. Neuromonitoring and neurocognitive/neurodevelopmental follow-up are critically important to optimize outcomes in both adults and children. OBJECTIVE: To assess current practice of neuromonitoring during ECMO and neurocognitive/neurodevelopmental follow-up after ECMO across Europe and to inform the development of neuromonitoring and follow-up guidelines. METHODS: The EuroELSO Neurological Monitoring and Outcome Working Group conducted an electronic, web-based, multi-institutional, multinational survey in Europe. RESULTS: Of the 211 European ECMO centres (including non-ELSO centres) identified and approached in 23 countries, 133 (63%) responded. Of these, 43% reported routine neuromonitoring during ECMO for all patients, 35% indicated selective use, and 22% practiced bedside clinical examination alone. The reported neuromonitoring modalities were NIRS (n = 88, 66.2%), electroencephalography (n = 52, 39.1%), transcranial Doppler (n = 38, 28.5%) and brain injury biomarkers (n = 33, 24.8%). Paediatric centres (67%) reported using cranial ultrasound, though the frequency of monitoring varied widely. Before hospital discharge following ECMO, 50 (37.6%) reported routine neurological assessment and 22 (16.5%) routinely performed neuroimaging with more paediatric centres offering neurological assessment (65%) as compared to adult centres (20%). Only 15 (11.2%) had a structured longitudinal follow-up pathway (defined followup at regular intervals), while 99 (74.4%) had no follow-up programme. The majority (n = 96, 72.2%) agreed that there should be a longitudinal structured follow-up for ECMO survivors. CONCLUSIONS: This survey demonstrated significant variability in the use of different neuromonitoring modalities during and after ECMO. The perceived importance of neuromonitoring and follow-up was noted to be very high with agreement for a longitudinal structured follow-up programme, particularly in paediatric patients. Scientific society endorsed guidelines and minimum standards should be developed to inform local protocols.

[Recommendations of the S3 Guideline "Use of Extracorporeal Circulation (ECLS/ ECMO) for Cardiac and Circulatory Failure" of the Association of Scientific Medical Societies in Germany]. / Empfehlungen der S3-Leitlinie (AWMF) "Einsatz der extrakorporalen Zirkulation (ECLS/ECMO) bei Herz- und Kreislaufversagen".

In recent years, the use of mechanical support for patients with cardiac or circulatory failure has continuously increased, leading to 3,000 ECLS/ECMO (extracorporeal life support/extracorporeal membrane oxygenation) implantations annually in Germany. Due to the lack of guidelines, there is an urgent need for evidence-based recommendations addressing the central aspects of ECLS/ECMO therapy. In July 2015, the generation of a guideline level S3 according to the standards of the Association of the Scientific Medical Societies in Germany (AWMF) was announced by the German Society for Thoracic and Cardiovascular Surgery (GSTCVS). In a well-structured consensus process, involving experts from Germany, Austria and Switzerland, delegated by 16 scientific societies and the patients' representation, the guideline "Use of extracorporeal circulation (ECLS/ECMO) for cardiac and circulatory failure" was created under guidance of the GSTCVS, and published in February 2021. The guideline focuses on clinical aspects of initiation, continuation, weaning and aftercare, herein also addressing structural and economic issues. This article presents an overview on the methodology as well as the final recommendations.

[Extracorporeal Life Support in Critical Care Medicine]. / Extrakorporaler Life Support in der Intensivmedizin.

Veno-arterial extracorporeal life support (ECLS) may be indicated in patients with refractory heart failure. The list of conditions in which ECLS is successfully used is growing and includes cardiogenic shock following myocardial infarction, refractory cardiac arrest, septic shock with low cardiac output and severe intoxication. Femoral ECLS is the most common and often preferred ECLS-configuration in the emergency setting. Although femoral access is usually quick and easy to establish, it is also associated with specific adverse haemodynamic effects due to the direction of blood flow and access-site complications are inherent. Femoral ECLS provides adequate oxygen delivery and compensates for impaired cardiac output. However, retrograde blood flow into the aorta increases left ventricular afterload and may worsen left ventricular stroke work. Therefore, femoral ECLS is not equivalent to left ventricular unloading. Daily haemodynamic assessments are crucial and should include echocardiography and laboratory tests determining tissue oxygenation. Common complications include the harlequin-phenomenon, lower limb ischaemia or cerebral events and cannula site or intracranial bleeding. Despite a high incidence of complications and high mortality, ECLS is associated with survival benefits and better neurological outcomes in selected patient groups.

[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.

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 life support in patients with acute myocardial infarction complicated by cardiogenic shock - Design and rationale of the ECLS-SHOCK trial.

BACKGROUND: In acute myocardial infarction complicated by cardiogenic shock the use of mechanical circulatory support devices remains controversial and data from randomized clinical trials are very limited. Extracorporeal life support (ECLS) - venoarterial extracorporeal membrane oxygenation - provides the strongest hemodynamic support in addition to oxygenation. However, despite increasing use it has not yet been properly investigated in randomized trials. Therefore, a prospective randomized adequately powered clinical trial is warranted. STUDY DESIGN: The ECLS-SHOCK trial is a 420-patient controlled, international, multicenter, randomized, open-label trial. It is designed to compare whether treatment with ECLS in addition to early revascularization with percutaneous coronary intervention or alternatively coronary artery bypass grafting and optimal medical treatment is beneficial in comparison to no-ECLS in patients with severe infarct-related cardiogenic shock. Patients will be randomized in a 1:1 fashion to one of the two treatment arms. The primary efficacy endpoint of ECLS-SHOCK is 30-day mortality. Secondary outcome measures such as hemodynamic, laboratory, and clinical parameters will serve as surrogate endpoints for prognosis. Furthermore, a longer follow-up at 6 and 12 months will be performed including quality of life assessment. Safety endpoints include peripheral ischemic vascular complications, bleeding and stroke. CONCLUSIONS: The ECLS-SHOCK trial will address essential questions of efficacy and safety of ECLS in addition to early revascularization in acute myocardial infarction complicated by cardiogenic shock.

Pulmonary Hemodynamics and Ventilation in Patients With COVID-19-Related Respiratory Failure and ARDS.

BACKGROUND: It has been suggested that COVID-19-associated severe respiratory failure (CARDS) might differ from usual acute respiratory distress syndrome (ARDS) due to failing autoregulation of pulmonary vessels and higher shunt. We sought to investigate pulmonary hemodynamics and ventilation properties in patients with CARDS compared to patients with ARDS of pulmonary origin. METHODS: This was a retrospective analysis of prospectively collected data from consecutive adults with laboratory-confirmed severe acute respiratory syndrome coronavirus 2 patients treated in our ICU in 04/2020 and a comparison of the data to matched controls with ARDS due to respiratory infections treated in our ICU from 01/2014 to 08/2019 for whom pulmonary artery catheter data were available. RESULTS: CARDS patients (n = 10) had ventilation characteristics similar to those of ARDS (n = 10) patients. Nevertheless, mechanical power applied by ventilation was significantly higher in CARDS patients (23.4 ± 8.9 J/min) than in ARDS (15.9 ± 4.3 J/min; P < 0.05). COVID-19 patients had similar pulmonary artery pressure but significantly lower pulmonary vascular resistance, as cardiac output was higher in CARDS vs. ARDS patients (P < 0.05). Shunt fraction and dead space were similar in CARDS compared to ARDS (P > 0.05) and were correlated with hypoxemia in both groups. The arteriovenous pCO2 difference (▵pCO2) was elevated (CARDS 5.5 ± 2.8 mmHg vs. ARDS 4.7 ± 1.1 mmHg; P > 0.05), as was the P(v-a)CO2/C(a-v)O2 ratio (CARDS mean 2.2 ± 1.5 vs. ARDS 1.7 ± 0.8; P > 0.05). CONCLUSIONS: Respiratory failure in COVID-19 patients seems to differ only slightly from ARDS regarding ventilation characteristics and pulmonary hemodynamics. Our data indicate microcirculatory dysfunction. More data need to be collected to assure these findings and gain more pathophysiological insights into COVID-19 and respiratory failure.

Effects of inhaled nitric oxide in COVID-19-induced ARDS - Is it worthwhile?

BACKGROUND: Changes in pulmonary hemodynamics and ventilation/perfusion were proposed as hallmarks of Coronavirus disease 2019 (COVID-19)-induced acute respiratory distress syndrome (ARDS). Inhaled nitric oxide (iNO) may overcome these issues and improve arterial oxygenation. METHODS: We retrospectively analyzed arterial oxygenation and pulmonary vasoreactivity in seven COVID-19 ARDS patients receiving 20 ppm iNO for 15-30 minutes. RESULTS: The inhalation of NO significantly improved oxygenation. All patients with severe ARDS had higher partial pressures of oxygen and reduced pulmonary vascular resistance. Significant changes in pulmonary shunting were not observed. CONCLUSION: Overall, iNO could provide immediate help and delay respiratory deterioration in COVID-19-induced moderate to severe ARDS.

Extracorporeal life support in COVID-19-related acute respiratory distress syndrome: A EuroELSO international survey.

Extracorporeal life support (ECLS) is a means to support patients with acute respiratory failure. Initially, recommendations to treat severe cases of pandemic coronavirus disease 2019 (COVID-19) with ECLS have been restrained. In the meantime, ECLS has been shown to produce similar outcomes in patients with severe COVID-19 compared to existing data on ARDS mortality. We performed an international email survey to assess how ECLS providers worldwide have previously used ECLS during the treatment of critically ill patients with COVID-19. A questionnaire with 45 questions (covering, e.g., indication, technical aspects, benefit, and reasons for treatment discontinuation), mostly multiple choice, was distributed by email to ECLS centers. The survey was approved by the European branch of the Extracorporeal Life Support Organization (ELSO); 276 ECMO professionals from 98 centers in 30 different countries on four continents reported that they employed ECMO for very severe COVID-19 cases, mostly in veno-venous configuration (87%). The most common reason to establish ECLS was isolated hypoxemic respiratory failure (50%), followed by a combination of hypoxemia and hypercapnia (39%). Only a small fraction of patients required veno-arterial cannulation due to heart failure (3%). Time on ECLS varied between less than 2 and more than 4 weeks. The main reason to discontinue ECLS treatment prior to patient's recovery was lack of clinical improvement (53%), followed by major bleeding, mostly intracranially (13%). Only 4% of respondents reported that triage situations, lack of staff or lack of oxygenators, were responsible for discontinuation of ECLS support. Most ECLS physicians (51%, IQR 30%) agreed that patients with COVID-19-induced ARDS (CARDS) benefitted from ECLS. Overall mortality of COVID-19 patients on ECLS was estimated to be about 55%. ECLS has been utilized successfully during the COVID-19 pandemic to stabilize CARDS patients in hypoxemic or hypercapnic lung failure. Age and multimorbidity limited the use of ECLS. Triage situations were rarely a concern. ECLS providers stated that patients with severe COVID-19 benefitted from ECLS.

Pumpless Extracorporeal Hemadsorption Technique: A New Method for Early Cytokine Elimination?

In recent years, extracorporeal hemadsorption (HA) techniques capable of adsorbing pro- and anti-inflammatory cytokines are increasingly used in various clinical situations. The therapeutic benefit of cytokine elimination likely depends on timing. Although treatment seems to be most effective when started within the first 24 h, therapy is often delayed as it must be combined with another extracorporeal circuit. Thus, using a pumpless extracorporeal HA technique might be a valuable option in order to expedite the commencement of cytokine elimination in critically ill patients.

[Extracorporeal cardiopulmonary resuscitation (eCPR) for out-of-hospital cardiac arrest (OHCA) : Retrospective analysis of a load and go strategy under the aspect of golden hour of eCPR]. / Extrakorporale kardiopulmonale Reanimation (eCPR) bei prähospitalem Herz-Kreislauf-Stillstand (OHCA) : Retrospektive Analyse einer "Load-and-go"-Strategie unter dem Aspekt "golden hour of eCPR".

BACKGROUND: Survival rates after an out-of-hospital cardiac arrest (OHCA) remain low. Extracorporeal cardiopulmonary resuscitation (eCPR) has been introduced as an attempt to increase survival in selected patients and observational studies have shown promising results. Nevertheless, inclusion criteria and timing of eCPR remain undefined. OBJECTIVE: The current study analyzed a load and go strategy with respect to the golden hour of eCPR as a cut-off time for survival and favorable neurological outcome. MATERIAL AND METHODS: This retrospective cohort study included 32 patients who underwent eCPR treatment due to an OHCA between January 2017 and September 2019. Routinely taken patient demographic data (age, BMI, sex) were analyzed. The main focus was set on processing times in the preclinical and clinical setting. Time intervals including OHCA until ambulance arrival, time on scene, transportation times and door to eCPR were extracted from emergency medical service (EMS) and resuscitation protocols. Low-flow times, survival and neurological outcome were analyzed. RESULTS: The use of eCPR in OHCA was associated with survival to hospital discharge in 28% and a good neurological outcome in 19% of the cases. Both groups (survivor and nonsurvivor) did not differ in patient demographics except for age. Survivors were significantly younger (47 (30-60) vs. 59 (50-68) years, p = 0.035). Processing times as well as low-flow times were not significantly different (OHCA-eCPR survivor 64 (50-87) vs. non-survivor 74 (51-85) min; p-value 0.64); however, median low-flow times were outside the golden hour of eCPR (69 (52-86)). CONCLUSION: Despite low-flow times of more than 60 min, eCPR was associated with survival in 28% after OHCA. Hence, exceeding the golden hour of eCPR cannot act as a definitive exclusion criterion for eCPR.

[Training module extracorporeal life support (ECLS): consensus statement of the DIVI, DGTHG, DGfK, DGAI, DGIIN, DGF, GRC and DGK]. / Ausbildungsmodul Extrakorporaler Life Support (ECLS): Konsensuspapier der DIVI, DGTHG, DGfK, DGAI, DGIIN, DGF, GRC und der DGK.

Mechanical circulatory support using extracorporeal life support systems (ECLS) has significantly increased in recent years. These critically ill patients pose special challenges to the multiprofessional treatment team and require comprehensive, interdisciplinary and interprofessional concepts. For this reason, to ensure the best possible patient care a standardized ECLS training module has been created at national specialist society level, taking emergency and intensive care management into account.

[Use of extracorporeal circulation (ECLS/ECMO) for cardiac and circulatory failure : Short version of the S3 guideline]. / Einsatz der extrakorporalen Zirkulation (ECLS/ECMO) bei Herz- und Kreislaufversagen : Kurzversion der AWMF-S3-Leitlinie.

In Germany, a remarkable increase regarding the usage of extracorporeal membrane oxygenation (ECMO) and extracorporeal life support (ECLS) systems has been observed in recent years with approximately 3000 ECLS/ECMO implantations annually since 2015. Despite the widespread use of ECLS/ECMO, evidence-based recommendations or guidelines are still lacking regarding indications, contraindications, limitations and management of ECMO/ECLS patients. Therefore in 2015, the German Society of Thoracic and Cardiovascular Surgery (GSTCVS) registered the multidisciplinary S3 guideline "Use of extracorporeal circulation (ECLS/ECMO) for cardiac and circulatory failure" to develop evidence-based recommendations for ECMO/ECLS systems according to the requirements of the Association of the Scientific Medical Societies in Germany (AWMF). Although the clinical application of ECMO/ECLS represents the main focus, the presented guideline also addresses structural and economic issues. Experts from 17 German, Austrian and Swiss scientific societies and a patients' organization, guided by the GSTCVS, completed the project in February 2021. In this report, we present a summary of the methodological concept and tables displaying the recommendations for each chapter of the guideline.

Redistribution of pulmonary ventilation after lung surgery detected with electrical impedance tomography.

BACKGROUND: Regional ventilation of the lung can be visualized by pulmonary electrical impedance tomography (EIT). The aim of this study was to examine the post-operative redistribution of regional ventilation after lung surgery dependent on the side of surgery and its association with forced vital capacity. METHODS: In this prospective, observational cohort study 13 patients undergoing right and 13 patients undergoing left-sided open or video-thoracoscopic procedures have been investigated. Pre-operative measurements with EIT and spirometry were compared with data obtained 3 days post-operation. The center of ventilation (COV) within a 32 × 32 pixel matrix was calculated from EIT data. The transverse axis coordinate of COV, COVx (left/right), was modified to COVx' (ipsilateral/contralateral). Thus, COVx' shows a negative change if ventilation shifts contralateral independent of the side of surgery. This enabled testing with two-way ANOVA for repeated measurements (side, time). RESULTS: The perioperative shift of COVx' was dependent on the side of surgery (P = .007). Ventilation shifted away from the side of surgery after the right-sided surgery (COVx'-1.97 pixel matrix points, P < .001), but not after the left-sided surgery (COVx'-0.61, P = .425). The forced vital capacity (%predicted) decreased from 94 (83-109)% (median [quartiles]; [left-sided]) and 89 (80-97)% (right-sided surgery) to 61 (59-66)% and 62 (40-72)% (P < .05), respectively. The perioperative changes in forced vital capacity (%predicted) were weakly associated with the shift of COVx'. CONCLUSION: Only after right-sided lung surgery, EIT showed reduced ventilation on the side of surgery while vital capacity was markedly reduced in both groups.

[Update Extracorporeal Lung Support]. / Organersatzverfahren: Update Lungenersatzverfahren.

Extracorporeal lung support is increasingly implemented worldwide in clinical practice in patients with severe acute respiratory distress syndrome (ARDS) and is required when mechanical ventilation is unable to establish sufficient pulmonary gas exchange or if the respirator settings are persistent elevated with an increased risk for ventilator induced lung injury (VILI). Besides that, hypercapnic respiratory failure in patients with acute exacerbation of COPD (AECOPD) or acute respiratory syndrome (ARDS) is common and may require extracorporeal elimination of carbon dioxide by ECCO2R, which also has been increasingly used in the clinical setting. For both therapeutic regimes there is up to date no clear evidence for a significant reduction in mortality in patients with ARDS. Therefore extracorporeal lung support should be still considered as a rescue therapy. In this review, based on a selective literature research and clinical experience of the authors, management of patients with extracorporeal lung assist, focusing on ECMO and ECCO2R is summarized.

Perioperative redistribution of regional ventilation and pulmonary function: a prospective observational study in two cohorts of patients at risk for postoperative pulmonary complications.

BACKGROUND: Postoperative pulmonary complications (PPCs) increase morbidity and mortality of surgical patients, duration of hospital stay and costs. Postoperative atelectasis of dorsal lung regions as a common PPC has been described before, but its clinical relevance is insufficiently examined. Pulmonary electrical impedance tomography (EIT) enables the bedside visualization of regional ventilation in real-time within a transversal section of the lung. Dorsal atelectasis or effusions might cause a ventral redistribution of ventilation. We hypothesized the existence of ventral redistribution in spontaneously breathing patients during their recovery from abdominal and peripheral surgery and that vital capacity is reduced if regional ventilation shifts to ventral lung regions. METHODS: This prospective observational study included 69 adult patients undergoing elective surgery with an expected intermediate or high risk for PPCs. Patients undergoing abdominal and peripheral surgery were recruited to obtain groups of equal size. Patients received general anesthesia with and without additional regional anesthesia. On the preoperative, the first and the third postoperative day, EIT was performed at rest and during spirometry (forced breathing). The center of ventilation in dorso-ventral direction (COVy) was calculated. RESULTS: Both groups received intraoperative low tidal volume ventilation. Postoperative ventral redistribution of ventilation (forced breathing COVy; preoperative: 16.5 (16.0-17.3); first day: 17.8 (16.9-18.2), p < 0.004; third day: 17.4 (16.2-18.2), p = 0.020) and decreased forced vital capacity in percentage of predicted values (FVC%predicted) (median: 93, 58, 64%, respectively) persisted after abdominal surgery. In addition, dorsal to ventral shift was associated with a decrease of the FVC%predicted on the third postoperative day (r = - 0.66; p < 0.001). A redistribution of pulmonary ventilation was not observed after peripheral surgery. FVC%predicted was only decreased on the first postoperative day (median FVC%predicted on the preoperative, first and third day: 85, 81 and 88%, respectively). In ten patients occurred pulmonary complications after abdominal surgery also in two patients after peripheral surgery. CONCLUSIONS: After abdominal surgery ventral redistribution of ventilation persisted up to the third postoperative day and was associated with decreased vital capacity. The peripheral surgery group showed only minor changes in vital capacity, suggesting a role of the location of surgery for postoperative redistribution of pulmonary ventilation. TRIAL REGISTRATION: This prospective observational single centre study was submitted to registration prior to patient enrollment at ClinicalTrials.gov (NCT02419196, Date of registration: December 1, 2014). Registration was finalized at April 17, 2015.

Targeted temperature management in patients undergoing extracorporeal life support after out-of-hospital cardiac arrest: an EURO-ELSO 2018 annual conference survey.

Targeted temperature management and extracorporeal life support, particularly extracorporeal membrane oxygenation in patients undergoing cardiopulmonary resuscitation, represent outcome-enhancing strategies for patients following in- and out-of-hospital cardiac arrest. Although targeted temperature management with hypothermia between 32°C and 34°C and extracorporeal cardiopulmonary resuscitation bear separate potentials to improve outcome after out-of-hospital cardiac arrest, each is associated with bleeding risk and risk of infection. Whether the combination imposes excessive risk on patients is, however, unknown.