Comparison of bleeding and thrombotic outcomes in veno-venous extracorporeal membrane oxygenation: Heparin versus bivalirudin.

OBJECTIVES: We aimed to evaluate thrombotic and hemorrhagic complications with heparin versus bivalirudin use in veno-venous extracorporeal membrane oxygenation (V-V ECMO). METHODS: We performed a retrospective cohort study of adult patients placed on V-V ECMO with intravenous anticoagulation with either heparin or bivalirudin. Time to thrombotic event and major bleed were analyzed in addition to related outcomes. RESULTS: We identified 95 patients placed on V-V ECMO: 61 receiving heparin, 34 bivalirudin. The bivalirudin group had a higher rate of severe COVID-19, higher BMI, and longer ECMO duration. Despite this, bivalirudin was associated with reduced risk of thrombotic event (HR 0.14, 95% CI 0.06-0.32, p < .001) and increased average lifespan of the circuit membrane lung (16 vs. 10 days, p = 0.004). While there was no difference in major bleeding, the bivalirudin group required fewer transfusions of packed red blood cells and platelets per 100 ECMO days (means of 13 vs. 39, p = 0.004; 5 vs. 19, p = .014, respectively). Lastly, the bivalirudin group had improved survival to ECMO decannulation in univariate analysis (median OS 53 vs. 26 days, p = .015). CONCLUSIONS: In this real-world analysis of bivalirudin versus heparin, bivalirudin is a viable option for V-V ECMO and associated with lower risk of thrombotic complications and fewer transfusion requirements.

Predictors of thrombosis during VV ECMO: an analysis of 9809 patients from the ELSO registry.

Venovenous extracorporeal membrane oxygenation (VV-ECMO) is a life-saving therapy for critically ill patients, but it carries an increased risk of thrombosis due to blood interacting with non-physiological surfaces. While the relationship between clinical variables and thrombosis remains unclear, our study aimed to identify which factors are most predictive of thrombosis. The Extracorporeal Life Support Organization Registry was queried to obtain a cohort of VV-ECMO patients aged 18 years and older from 2015 to 2019. Patients who were over 80-years-old, at the extremes of weight, who received less than 24 h of ECMO, multiple rounds of ECMO, or had missing data were excluded. Multivariate logistic regression modeling was used to assess predictors of thrombosis and mortality. A total of 9809 patients were included in the analysis, with a mean age of 47.1 ± 15.1 years and an average ECMO run time of 305 ± 353 h. Thrombosis occurred in 19.9% of the cohort, with circuit thrombosis (8.6%) and membrane lung failure (6.1%) being the most common. Multivariate analysis showed that ECMO runs over 14 days (OR: 2.62, P < 0.001) and pregnancy-related complications (OR: 1.79, P = 0.004) were associated with an increased risk of thrombosis. Risk factors for circuit thrombosis included incremental unit increases in the pump flow rate at 24 h (OR: 1.07 [1.00-1.14], P = 0.044) and specific cannulation sites. Increased body weight (OR: 1.02 [1.00-1.04], P = 0.026) and increased duration on ECMO (OR: 3.82 [3.12-4.71], P < 0.001) were predictive of membrane lung failure. Additionally, patients with thrombosis were at increased likelihood of in-hospital mortality (OR: 1.52, P < 0.001). This study identified multiple thrombotic risk factors in VV-ECMO, suggesting that future studies investigating the impact of pregnancy associated complications and ECMO flow rate on hemostasis would be illuminating.

Targeting the Contact Pathway of Coagulation for the Prevention and Management of Medical Device-Associated Thrombosis.

Hemorrhage remains a major complication of anticoagulants, with bleeding leading to serious and even life-threatening outcomes in rare settings. Currently available anticoagulants target either multiple coagulation factors or specifically coagulation factor (F) Xa or thrombin; however, inhibiting these pathways universally impairs hemostasis. Bleeding complications are especially salient in the medically complex population who benefit from medical devices. Extracorporeal devices-such as extracorporeal membrane oxygenation, hemodialysis, and cardiac bypass-require anticoagulation for optimal use. Nonetheless, bleeding complications are common, and with certain devices, highly morbid. Likewise, pharmacologic prophylaxis to prevent thrombosis is not commonly used with many medical devices like central venous catheters due to high rates of bleeding. The contact pathway members FXI, FXII, and prekallikrein serve as a nexus, connecting biomaterial surface-mediated thrombin generation and inflammation, and may represent safe, druggable targets to improve medical device hemocompatibility and thrombogenicity. Recent in vivo and clinical data suggest that selectively targeting the contact pathway of coagulation through the inhibition of FXI and FXII can reduce the incidence of medical device-associated thrombotic events, and potentially systemic inflammation, without impairing hemostasis. In the following review, we will outline the current in vivo and clinical data encompassing the mechanism of action of drugs targeting the contact pathway. This new class of inhibitors has the potential to herald a new era of effective and low-risk anticoagulation for the management of patients requiring the use of medical devices.

Interfacility Transport of Critically Ill Patients.

OBJECTIVES: To assess recent advances in interfacility critical care transport. DATA SOURCES: PubMed English language publications plus chapters and professional organization publications. STUDY SELECTION: Manuscripts including practice manuals and standard (1990-2021) focused on interfacility transport of critically ill patients. DATA EXTRACTION: Review of society guidelines, legislative requirements, objective measures of outcomes, and transport practice standards occurred in work groups assessing definitions and foundations of interfacility transport, transport team composition, and transport specific considerations. Qualitative analysis was performed to characterize current science regarding interfacility transport. DATA SYNTHESIS: The Task Force conducted an integrative review of 496 manuscripts combined with 120 from the authors' collections including nonpeer reviewed publications. After title and abstract screening, 40 underwent full-text review, of which 21 remained for qualitative synthesis. CONCLUSIONS: Since 2004, there have been numerous advances in critical care interfacility transport. Clinical deterioration may be mitigated by appropriate patient selection, pretransport optimization, and transport by a well-resourced team and vehicle. There remains a dearth of high-quality controlled studies, but notable advances in monitoring, en route management, transport modality (air vs ground), as well as team composition and training serve as foundations for future inquiry. Guidance from professional organizations remains uncoupled from enforceable regulations, impeding standardization of transport program quality assessment and verification.

Severe thrombocytopenia in adults undergoing extracorporeal membrane oxygenation is predictive of thrombosis.

Extracorporeal membrane oxygenation (ECMO) provides lifesaving circulatory support and gas exchange, although hematologic complications are frequent. The relationship between ECMO and severe thrombocytopenia (platelet count <50 × 109/L) remains ill-defined. We performed a cohort study of 67 patients who received ECMO between 2016 and 2019, of which 65.7% received veno-arterial (VA) ECMO and 34.3% received veno-venous (VV) ECMO. All patients received heparin and 25.4% received antiplatelet therapy. In total, 23.9% of patients had a thrombotic event and 67.2% had a hemorrhagic event. 38.8% of patients developed severe thrombocytopenia. Severe thrombocytopenia was more common in patients with lower baseline platelet counts and increased the likelihood of thrombosis by 365% (OR 3.65, 95% CI 1.13-11.8, P = .031), while the type of ECMO (VA or VV) was not predictive of severe thrombocytopenia (P = .764). Multivariate logistic regression controlling for additional clinical variables found that severe thrombocytopenia predicted thrombosis (OR 3.65, CI 1.13-11.78, P = .031). Over a quarter of patients requiring ECMO developed severe thrombocytopenia in our cohort, which was associated with an increased risk of thrombosis and in-hospital mortality. Additional prospective observation is required to clarify the clinical implications of severe thrombocytopenia in the ECMO patient population.

ECLS in Trauma: Practical Application and a Review of Current Status.

Extracorporeal life support has evolved considerably over the past two decades. Once considered as salvage or experimental therapy in adults, extracorporeal membrane oxygenation (ECMO) is evolving into a mainstream treatment for adult critical care. This is especially true in trauma and high-risk surgical patients, who have traditionally been excluded from consideration. Several technological advances have made this possible. This includes anticoagulant-bonded circuits, device miniaturization, servo-regulated centrifugal systems, and more efficient oxygenators. Adult ECMO may now be rapidly deployed for severe acute respiratory distress syndrome (ARDS) and cardiogenic shock. Trauma and surgical patients with severe ARDS should be considered for ECMO early in their clinical course to provide optimal lung rest.

Retrospective Analysis of Long-Term Outcomes After Combat Injury: A Hidden Cost of War.

BACKGROUND: During the conflicts in Iraq and Afghanistan, 52,087 service members have been wounded in combat. The long-term sequelae of these injuries have not been carefully examined. We sought to determine the relation between markers of injury severity and the subsequent development of hypertension, coronary artery disease, diabetes mellitus, and chronic kidney disease. METHODS AND RESULTS: Retrospective cohort study of critically injured US military personnel wounded in Iraq or Afghanistan from February 1, 2002 to February 1, 2011. Patients were then followed until January 18, 2013. Chronic disease outcomes were assessed by International Classification of Diseases, 9th edition codes and causes of death were confirmed by autopsy. From 6011 admissions, records were excluded because of missing data or if they were for an individual's second admission. Patients with a disease diagnosis of interest before the injury date were also excluded, yielding a cohort of 3846 subjects for analysis. After adjustment for other factors, each 5-point increment in the injury severity score was associated with a 6%, 13%, 13%, and 15% increase in incidence rates of hypertension, coronary artery disease, diabetes mellitus, and chronic kidney disease, respectively. Acute kidney injury was associated with a 66% increase in rates of hypertension and nearly 5-fold increase in rates of chronic kidney disease. CONCLUSIONS: In Iraq and Afghanistan veterans, the severity of combat injury was associated with the subsequent development of hypertension, coronary artery disease, diabetes mellitus, and chronic kidney disease.

Advanced extracorporeal therapy in trauma.

PURPOSE OF REVIEW: The purpose is to review the current application of extracorporeal life support (ECLS) in trauma patients. In addition, programmatic development is described. RECENT FINDINGS: ECLS use is increasing among trauma patients. Several recent studies among trauma patients report survival rates of 65-79%. Despite the high bleeding risk, extracorporeal membrane oxygenation (ECMO) may be safely implemented in trauma patients based on a strict protocol-driven policy. Early implementation may improve overall outcomes. Alternative anticoagulants and heparin free periods may be well tolerated in trauma patients at high risk of hemorrhage. SUMMARY: ECMO is becoming a more routine option in severely injured trauma patients that develop severe respiratory failure. Well tolerated implementation and program development is possible among regional trauma centers. Although clinical knowledge gaps exist, ECMO is a promising treatment in this high-risk population.

Disrupted modular organization of resting-state cortical functional connectivity in U.S. military personnel following concussive 'mild' blast-related traumatic brain injury.

Blast-related traumatic brain injury (TBI) has been one of the "signature injuries" of the wars in Iraq and Afghanistan. However, neuroimaging studies in concussive 'mild' blast-related TBI have been challenging due to the absence of abnormalities in computed tomography or conventional magnetic resonance imaging (MRI) and the heterogeneity of the blast-related injury mechanisms. The goal of this study was to address these challenges utilizing single-subject, module-based graph theoretic analysis of resting-state functional MRI (fMRI) data. We acquired 20min of resting-state fMRI in 63 U.S. military personnel clinically diagnosed with concussive blast-related TBI and 21 U.S. military controls who had blast exposures but no diagnosis of TBI. All subjects underwent an initial scan within 90days post-injury and 65 subjects underwent a follow-up scan 6 to 12months later. A second independent cohort of 40 U.S. military personnel with concussive blast-related TBI served as a validation dataset. The second independent cohort underwent an initial scan within 30days post-injury. 75% of the scans were of good quality, with exclusions primarily due to excessive subject motion. Network analysis of the subset of these subjects in the first cohort with good quality scans revealed spatially localized reductions in the participation coefficient, a measure of between-module connectivity, in the TBI patients relative to the controls at the time of the initial scan. These group differences were less prominent on the follow-up scans. The 15 brain areas with the most prominent reductions in the participation coefficient were next used as regions of interest (ROIs) for single-subject analyses. In the first TBI cohort, more subjects than would be expected by chance (27/47 versus 2/47 expected, p<0.0001) had 3 or more brain regions with abnormally low between-module connectivity relative to the controls on the initial scans. On the follow-up scans, more subjects than expected by chance (5/37, p=0.044) but fewer subjects than on the initial scans had 3 or more brain regions with abnormally low between-module connectivity. Analysis of the second TBI cohort validation dataset with no free parameters provided a partial replication; again more subjects than expected by chance (8/31, p=0.006) had 3 or more brain regions with abnormally low between-module connectivity on the initial scans, but the numbers were not significant (2/27, p=0.276) on the follow-up scans. A single-subject, multivariate analysis by probabilistic principal component analysis of the between-module connectivity in the 15 identified ROIs, showed that 31/47 subjects in the first TBI cohort were found to be abnormal relative to the controls on the initial scans. In the second TBI cohort, 9/31 patients were found to be abnormal in identical multivariate analysis with no free parameters. Again, there were not substantial differences on the follow-up scans. Taken together, these results indicate that single-subject, module-based graph theoretic analysis of resting-state fMRI provides potentially useful information for concussive blast-related TBI if high quality scans can be obtained. The underlying biological mechanisms and consequences of disrupted between-module connectivity are unknown, thus further studies are required.