Hemorrhage and thrombosis in COVID-19-patients supported with extracorporeal membrane oxygenation: an international study based on the COVID-19 critical care consortium.

BACKGROUND: Extracorporeal membrane oxygenation (ECMO) is a rescue therapy in patients with severe acute respiratory distress syndrome (ARDS) secondary to COVID-19. While bleeding and thrombosis complicate ECMO, these events may also occur secondary to COVID-19. Data regarding bleeding and thrombotic events in COVID-19 patients on ECMO are sparse. METHODS: Using the COVID-19 Critical Care Consortium database, we conducted a retrospective analysis on adult patients with severe COVID-19 requiring ECMO, including centers globally from 01/2020 to 06/2022, to determine the risk of ICU mortality associated with the occurrence of bleeding and clotting disorders. RESULTS: Among 1,248 COVID-19 patients receiving ECMO support in the registry, coagulation complications were reported in 469 cases (38%), among whom 252 (54%) experienced hemorrhagic complications, 165 (35%) thrombotic complications, and 52 (11%) both. The hazard ratio (HR) for Intensive Care Unit mortality was higher in those with hemorrhagic-only complications than those with neither complication (adjusted HR = 1.60, 95% CI 1.28-1.99, p < 0.001). Death was reported in 617 of the 1248 (49.4%) with multiorgan failure (n = 257 of 617 [42%]), followed by respiratory failure (n = 130 of 617 [21%]) and septic shock [n = 55 of 617 (8.9%)] the leading causes. CONCLUSIONS: Coagulation disorders are frequent in COVID-19 ARDS patients receiving ECMO. Bleeding events contribute substantially to mortality in this cohort. However, this risk may be lower than previously reported in single-nation studies or early case reports. Trial registration ACTRN12620000421932 ( https://covid19.cochrane.org/studies/crs-13513201 ).

Race and ethnicity in the COVID-19 Critical Care Consortium: demographics, treatments, and outcomes, an international observational registry study.

BACKGROUND: Improving access to healthcare for ethnic minorities is a public health priority in many countries, yet little is known about how to incorporate information on race, ethnicity, and related social determinants of health into large international studies. Most studies of differences in treatments and outcomes of COVID-19 associated with race and ethnicity are from single cities or countries. METHODS: We present the breadth of race and ethnicity reported for patients in the COVID-19 Critical Care Consortium, an international observational cohort study from 380 sites across 32 countries. Patients from the United States, Australia, and South Africa were the focus of an analysis of treatments and in-hospital mortality stratified by race and ethnicity. Inclusion criteria were admission to intensive care for acute COVID-19 between January 14th, 2020, and February 15, 2022. Measurements included demographics, comorbidities, disease severity scores, treatments for organ failure, and in-hospital mortality. RESULTS: Seven thousand three hundred ninety-four adults met the inclusion criteria. There was a wide variety of race and ethnicity designations. In the US, American Indian or Alaska Natives frequently received dialysis and mechanical ventilation and had the highest mortality. In Australia, organ failure scores were highest for Aboriginal/First Nations persons. The South Africa cohort ethnicities were predominantly Black African (50%) and Coloured* (28%). All patients in the South Africa cohort required mechanical ventilation. Mortality was highest for South Africa (68%), lowest for Australia (15%), and 30% in the US. CONCLUSIONS: Disease severity was higher for Indigenous ethnicity groups in the US and Australia than for other ethnicities. Race and ethnicity groups with longstanding healthcare disparities were found to have high acuity from COVID-19 and high mortality. Because there is no global system of race and ethnicity classification, researchers designing case report forms for international studies should consider including related information, such as socioeconomic status or migration background. *Note: "Coloured" is an official, contemporary government census category of South Africa and is a term of self-identification of race and ethnicity of many citizens of South Africa.

Thrombotic and hemorrhagic complications of COVID-19 in adults hospitalized in high-income countries compared with those in adults hospitalized in low- and middle-income countries in an international registry.

Background: COVID-19 has been associated with a broad range of thromboembolic, ischemic, and hemorrhagic complications (coagulopathy complications). Most studies have focused on patients with severe disease from high-income countries (HICs). Objectives: The main aims were to compare the frequency of coagulopathy complications in developing countries (low- and middle-income countries [LMICs]) with those in HICs, delineate the frequency across a range of treatment levels, and determine associations with in-hospital mortality. Methods: Adult patients enrolled in an observational, multinational registry, the International Severe Acute Respiratory and Emerging Infections COVID-19 study, between January 1, 2020, and September 15, 2021, met inclusion criteria, including admission to a hospital for laboratory-confirmed, acute COVID-19 and data on complications and survival. The advanced-treatment cohort received care, such as admission to the intensive care unit, mechanical ventilation, or inotropes or vasopressors; the basic-treatment cohort did not receive any of these interventions. Results: The study population included 495,682 patients from 52 countries, with 63% from LMICs and 85% in the basic treatment cohort. The frequency of coagulopathy complications was higher in HICs (0.76%-3.4%) than in LMICs (0.09%-1.22%). Complications were more frequent in the advanced-treatment cohort than in the basic-treatment cohort. Coagulopathy complications were associated with increased in-hospital mortality (odds ratio, 1.58; 95% CI, 1.52-1.64). The increased mortality associated with these complications was higher in LMICs (58.5%) than in HICs (35.4%). After controlling for coagulopathy complications, treatment intensity, and multiple other factors, the mortality was higher among patients in LMICs than among patients in HICs (odds ratio, 1.45; 95% CI, 1.39-1.51). Conclusion: In a large, international registry of patients hospitalized for COVID-19, coagulopathy complications were more frequent in HICs than in LMICs (developing countries). Increased mortality associated with coagulopathy complications was of a greater magnitude among patients in LMICs. Additional research is needed regarding timely diagnosis of and intervention for coagulation derangements associated with COVID-19, particularly for limited-resource settings.

Is Fasciotomy Associated With Increased Mortality in Extracorporeal Cardiopulmonary Resuscitation?

Our primary objective was to identify if fasciotomy was associated with increased mortality in patients who developed acute compartment syndrome (ACS) on extracorporeal cardiopulmonary resuscitation (ECPR). Additionally, we sought to identify any additional risk factors for mortality in these patients and report the amputation-free survival following fasciotomy. We retrospectively reviewed adult ECPR patients from the Extracorporeal Life Support Organization registry who were diagnosed with ACS between 2013 and 2021. Of 764 ECPR patients with limb complications, 127 patients (17%) with ACS were identified, of which 78 (63%) had fasciotomies, and 14 (11%) had amputations. Fasciotomy was associated with a 23% rate of amputation-free survival. There were no significant differences in demographics or baseline laboratory values between those with and without fasciotomy. Overall, 88 of 127 (69%) patients with ACS died. With or without fasciotomy, the mortality of ACS patients was similar, 68% vs. 71%. Multivariable logistic regression demonstrated that body mass index (BMI; adjusted odds ratio [aOR] = 1.22, 95% confidence interval [CI] = 1.01-1.48) and 24 hour mean blood pressure (BP; aOR = 0.93, 95% CI = 0.88-0.99) were independently associated with mortality. Fasciotomy was not an independent risk factor for mortality (aOR = 0.24, 95% CI = 0.03-1.88). The results of this study may help guide surgical decision-making for patients who develop ACS after ECPR. However, the retrospective nature of this study does not preclude selection bias in patients who have received fasciotomy. Thus, prospective studies are necessary to confirm these findings.

Cerebrovascular Complications of COVID-19 on Venovenous Extracorporeal Membrane Oxygenation.

OBJECTIVES: Evidence of cerebrovascular complications in COVID-19 requiring venovenous extracorporeal membrane oxygenation (ECMO) is limited. Our study aims to characterize the prevalence and risk factors of stroke secondary to COVID-19 in patients on venovenous ECMO. DESIGN: We analyzed prospectively collected observational data, using univariable and multivariable survival modeling to identify risk factors for stroke. Cox proportional hazards and Fine-Gray models were used, with death and discharge treated as competing risks. SETTING: Three hundred eighty institutions in 53 countries in the COVID-19 Critical Care Consortium (COVID Critical) registry. PATIENTS: Adult COVID-19 patients who were supported by venovenous ECMO. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Five hundred ninety-five patients (median age [interquartile range], 51 yr [42-59 yr]; male: 70.8%) had venovenous ECMO support. Forty-three patients (7.2%) suffered strokes, 83.7% of which were hemorrhagic. In multivariable survival analysis, obesity (adjusted hazard ratio [aHR], 2.19; 95% CI, 1.05-4.59) and use of vasopressors before ECMO (aHR, 2.37; 95% CI, 1.08-5.22) were associated with an increased risk of stroke. Forty-eight-hour post-ECMO Pa co2 -pre-ECMO Pa co2 /pre-ECMO Pa co2 (relative ΔPa co2 ) of negative 26% and 48-hour post-ECMO Pa o2 -pre-ECMO Pa o2 /pre-ECMO Pa o2 (relative ΔPa o2 ) of positive 24% at 48 hours of ECMO initiation were observed in stroke patients in comparison to relative ΔPa co2 of negative 17% and relative ΔPa o2 of positive 7% in the nonstroke group. Patients with acute stroke had a 79% in-hospital mortality compared with 45% mortality for stroke-free patients. CONCLUSIONS: Our study highlights the association of obesity and pre-ECMO vasopressor use with the development of stroke in COVID-19 patients on venovenous ECMO. Also, the importance of relative decrease in Pa co2 and moderate hyperoxia within 48 hours after ECMO initiation were additional risk factors.

Hemorrhage, Disseminated Intravascular Coagulopathy, and Thrombosis Complications Among Critically Ill Patients with COVID-19: An International COVID-19 Critical Care Consortium Study.

OBJECTIVES: To determine the prevalence and outcomes associated with hemorrhage, disseminated intravascular coagulopathy, and thrombosis (HECTOR) complications in ICU patients with COVID-19. DESIGN: Prospective, observational study. SETTING: Two hundred twenty-nine ICUs across 32 countries. PATIENTS: Adult patients (≥ 16 yr) admitted to participating ICUs for severe COVID-19 from January 1, 2020, to December 31, 2021. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: HECTOR complications occurred in 1,732 of 11,969 study eligible patients (14%). Acute thrombosis occurred in 1,249 patients (10%), including 712 (57%) with pulmonary embolism, 413 (33%) with myocardial ischemia, 93 (7.4%) with deep vein thrombosis, and 49 (3.9%) with ischemic strokes. Hemorrhagic complications were reported in 579 patients (4.8%), including 276 (48%) with gastrointestinal hemorrhage, 83 (14%) with hemorrhagic stroke, 77 (13%) with pulmonary hemorrhage, and 68 (12%) with hemorrhage associated with extracorporeal membrane oxygenation (ECMO) cannula site. Disseminated intravascular coagulation occurred in 11 patients (0.09%). Univariate analysis showed that diabetes, cardiac and kidney diseases, and ECMO use were risk factors for HECTOR. Among survivors, ICU stay was longer (median days 19 vs 12; p < 0.001) for patients with versus without HECTOR, but the hazard of ICU mortality was similar (hazard ratio [HR] 1.01; 95% CI 0.92-1.12; p = 0.784) overall, although this hazard was identified when non-ECMO patients were considered (HR 1.13; 95% CI 1.02-1.25; p = 0.015). Hemorrhagic complications were associated with an increased hazard of ICU mortality compared to patients without HECTOR complications (HR 1.26; 95% CI 1.09-1.45; p = 0.002), whereas thrombosis complications were associated with reduced hazard (HR 0.88; 95% CI 0.79-0.99, p = 0.03). CONCLUSIONS: HECTOR events are frequent complications of severe COVID-19 in ICU patients. Patients receiving ECMO are at particular risk of hemorrhagic complications. Hemorrhagic, but not thrombotic complications, are associated with increased ICU mortality.

Beneficial Effect of Prone Positioning During Venovenous Extracorporeal Membrane Oxygenation for Coronavirus Disease 2019.

OBJECTIVES: The study investigated the impact of prone positioning during venovenous extracorporeal membrane oxygenation support for coronavirus disease 2019 acute respiratory failure on the patient outcome. DESIGN: An observational study of venovenous extracorporeal membrane oxygenation patients. We used a multistate survival model to compare the outcomes of patients treated with or without prone positioning during extracorporeal membrane oxygenation, which incorporates the dynamic nature of prone positioning and adjusts for potential confounders. SETTING: Seventy-two international institutions participating in the Coronavirus Disease 2019 Critical Care Consortium international registry. PATIENTS: Coronavirus disease 2019 patients who were supported by venovenous extracorporeal membrane oxygenation during the study period. INTERVENTION: None. MEASUREMENTS AND MAIN RESULTS: There were 232 coronavirus disease 2019 patients at 72 participating institutions who were supported with venovenous extracorporeal membrane oxygenation during the study period from February 16, 2020, to October 31, 2020. Proning was used in 176 patients (76%) before initiation of extracorporeal membrane oxygenation and in 67 patients (29%) during extracorporeal membrane oxygenation. Survival to hospital discharge was 33% in the extracorporeal membrane oxygenation prone group versus 22% in the extracorporeal membrane oxygenation supine group. Prone positioning during extracorporeal membrane oxygenation support was associated with reduced mortality (hazard ratio, 0.31; 95% CI, 0.14-0.68). CONCLUSIONS: Our study highlights that prone positioning during venovenous extracorporeal membrane oxygenation support for refractory coronavirus disease 2019-related acute respiratory distress syndrome is associated with reduced mortality. Given the observational nature of the study, a randomized controlled trial of prone positioning on venovenous extracorporeal membrane oxygenation is needed to confirm these findings.

Echocardiography-Guided Dual-Lumen Venovenous Extracorporeal Membrane Oxygenation Cannula Placement in the ICU-A Retrospective Review.

OBJECTIVE: The most effective method of image guidance for venovenous extracorporeal membrane oxygenation is not known. The authors' objectives were to define the frequency of successful initial cannulation using echocardiographic guidance in the intensive care unit, as well as to determine the frequency of subsequent adjustments. Additional aims were to illustrate cannula malposition problems and to describe features associated with difficult cannulation. DESIGN: Retrospective consecutive case series analysis. SETTING: Single tertiary care university hospital. PARTICIPANTS: Forty-five patients treated with venovenous extracorporeal membrane oxygenation. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The most common causes of respiratory failure were pneumonia, aspiration, and inhalational burn injury. Sixty-two percent survived to discharge. Initial cannulation was successful in 39 cases (87%). Adverse events included 5 cases of cannula malposition and 1 case of hemorrhagic shock. During the course of extracorporeal membrane oxygenation, 17 patients (38%) required echo-guided cannula position adjustments. There were no fatal complications. Factors associated with difficult cannulation included extremes of size, a prominent Eustachian valve, and an anterior guidewire bending in the right atrium. Younger age was associated positively with survival. There was no significant association between adverse events during cannulation and survival. CONCLUSIONS: Dual-lumen venovenous extracorporeal membrane oxygenation cannulation in the intensive care unit under echo guidance has a high initial success rate, but many patients require subsequent repositioning. Echocardiography can define cannula position in sufficient detail to identify malposition precisely and to guide repositioning.

Transesophageal echocardiography in the evaluation of the trauma patient: A trauma resuscitation transesophageal echocardiography exam.

The point-of-care ultrasound exam has become an essential tool for hemodynamic monitoring and resuscitation in the trauma bay as well as the intensive care unit. Transthoracic ultrasound provides a dynamic assessment of cardiac function, volume status, and fluid responsiveness that offers potential advantage over traditional methods of hemodynamic monitoring. More recently, a focused transthoracic echocardiography exam was described to improve immediate resuscitation of severely injured patients in the trauma bay. Transesophageal echocardiography (TEE) for trauma could expand upon the role of focused echocardiography. TEE offers improved visualization of cardiac anatomy and physiology, improved diagnostic accuracy, and real-time assessment of intraoperative resuscitation progress, particularly in the operating room. This review discusses the fundamental principles of echocardiography as well as different ultrasound modes with their respective strengths and limitations. It reviews the current literature on the use of TEE in trauma, and suggests views for a trauma resuscitation transesophageal echocardiography exam (TREE), including sample images and videos.

The Effect of Perioperative Rescue Transesophageal Echocardiography on the Management of Trauma Patients.

To evaluate the effect of rescue transesophageal echocardiography (TEE) on the management of trauma patients, we reviewed imaging and charts of unstable trauma patients at a level I trauma center. Critical rescue TEE findings included acute right ventricular failure, stress cardiomyopathy, type B aortic dissection, mediastinal air, and dynamic left ventricular outflow tract obstruction. Left ventricular filling was classified as low (underfilled) in 57% of all cases. Rescue TEE revealed a variety of new diagnoses and led to a change in resuscitation strategy about half of the time.

A review of 364 perioperative rescue echocardiograms: findings of an anesthesiologist-staffed perioperative echocardiography service.

OBJECTIVE: Review the findings and use of rescue echocardiography performed by the Division of Perioperative Echocardiography and its impact on patient management. DESIGN: Retrospective observational study. SETTING: Single institution, tertiary care hospital. PARTICIPANTS: Three hundred sixty-four consecutive rescue echocardiograms in the perioperative setting. INTERVENTIONS: Rescue transesophageal or rescue transthoracic echocardiography. MEASUREMENTS AND MAIN RESULTS: Of a total of 1,675 perioperative echocardiograms performed in a 28-month period, 364 (21.8%) were rescue studies. Of these, 95.9% were transesophageal and 4.1% were transthoracic. Location at time of rescue echocardiography was intraoperative (55.5%), postoperative (44.2%), and preoperative (0.3%). No single diagnosis predominated the intraoperative or postoperative environment, and the frequency of common etiologies did not allow for assumption. There was a change in management for 214 patients (59%) as the result of findings. The methods used in performing rescue echocardiography at the authors' institution are reported. CONCLUSIONS: The heterogeneity of diagnoses and the frequency with which rescue echocardiography changed management further supports the growing body of evidence that the hemodynamically unstable perioperative patient benefits from its use.

The role of echocardiography in hemodynamic assessment of septic shock.

Echocardiography is a rapid, noninvasive, comprehensive cardiac assessment option for patients presenting with hemodynamic instability. In patients with septic shock, echocardiography can be used to guide fluid therapy by measuring collapsibility of the inferior vena cava. Sepsis-induced myocardial dysfunction can be diagnosed, and responses to therapy can be monitored with echo. Patients with persistent shock should be evaluated for right heart failure, dynamic left ventricular obstruction, or tamponade if they do not respond to resuscitation and norepinephrine. Unexpected or rare findings that affect management may be revealed using focused echocardiography. This article presents national and international competency statements regarding critical care echocardiography and training resources for intensivists.

Coagulation management in massive bleeding.

PURPOSE OF REVIEW: To update readers on recent literature regarding treatment of coagulopathy for patients with life-threatening bleeding, highlighting emerging therapeutic options, controversial topics, and ongoing clinical trials. RECENT FINDINGS: Massive transfusion protocols featuring immediate availability of blood products and multidisciplinary communication reduce mortality and conserve resources. There is a growing consensus that immediate administration of plasma and platelet units in a 1: 1: 1 ratio with red cell units reduces early mortality. Lyophilized and recombinant blood product components may have advantages over traditional blood products in certain clinical circumstances. SUMMARY: Massive transfusion protocols standardize treatment of the coagulopathy of massive bleeding, leading to rapid restoration of hemostasis and decrease in early mortality.