Coagulation Disorders and Management

Coronavirus Disease-19 (COVID-19), caused by SARS-CoV-2 infection, is associated with a rise in inflammatory markers which can result in altered coagulation system activation and regulation. During COVID-19, a remarkable tendency towards venous thrombosis and thrombo-embolism has been widely reported, especially in the critically ill patients. Thus, to limit this clinically relevant events, various strategies of venous thrombo-prophylaxis and anticoagulation have been studied. On the other hand, arterial thrombosis seems to play a less relevant role the clinical picture of COVID-19, as much as bleeding complications, which are mostly correlated to anticoagulation management. © The Editor(s) (if applicable) and The Author(s), under exclusive license to Springer Nature Switzerland AG 2022.

Extracorporeal corporeal membrane oxygenation: indications, technical considerations, and future trends

The extracorporeal membrane oxygenation (ECMO) device was initially developed with the goal of providing extended support in patients experiencing cardiac failure. However, ECMO technology has evolved, and now provides a means to successfully manage patients experiencing cardiac and/or pulmonary failure until such time as the patient's body is able to either heal, or undergo transplantation. In addition, it has been used in the management of multisystem organ dysfunction. The life-saving utility of this therapy for critically ill patients has prompted world-wide implementation particularly in resource-rich settings. Innovations in instrumentation, broad clinical implementation, extensive utilization of blood and blood components, and the catastrophic nature of potential complications, have collectively prompted the evolution of a tremendous body of research. In this comprehensive review we briefly describe the early development of the ECMO device and technology, in addition to outlining the function of the device as it now commonly utilized including veno-arterial (VA) vs. veno-venous (VV) and rapid deployment ECMO. This review will also delineate the rationale for ECMO use, common clinical indications, and specialized techniques, in addition to the approaches necessary for their successful implementation. As systemic anticoagulation is frequently utilized to support patients on ECMO, the review also contains an extensive review of anticoagulation management, blood component utilization, and potential hematologic complications of ECMO. The review includes a discussion of more recent trends including the use of ECMO in COVID-19 patients, and the performance of tandem plasma exchange. Finally, areas of current controversy and needed research will be highlighted. © 2022 The authors.

An appraisal of respiratory system compliance in mechanically ventilated COVID-19 patients

Rationale Heterogeneous respiratory system static compliance (CRS) values and levels of hypoxemia in patients with novel coronavirus disease (COVID-19) requiring mechanical ventilation have been reported in previous smallcase series or studies conducted at a national level.Methods We designed a retrospective observational cohort study with rapid data gathering from the international COVID-19 Critical Care Consortium study to comprehensively describe the impact of CRS on the ventilatory management and outcomes of COVID-19 patients on mechanical ventilation (MV), admitted to intensive care units (ICU) worldwide.Results We enrolled 318 COVID-19 patients enrolled into the study from January 14th through September 31th, 2020 in 19 countries and stratified into two CRS groups. CRS was calculated as: tidal volume/[airway plateau pressure-positive endexpiratory pressure (PEEP)] and available within 48h from commencement of MV in 318 patients. Patients were mean±SD of 58.0±12.2, predominantly from Europe (54%) and males (68%). Median CRS (IQR) was 34.1 mL/cmH2O (26.5-45.5) and PaO2/FiO2 was 119 mmHg (87.1-164) and was not correlated with CRS. Female sex presented lower CRS than in males (95% CI:-13.8 to-8.5 P<0.001) and higher body mass index (34.7±10.9 vs 29.1±6.0, p<0.001). Median (IQR) PEEP was 12 cmH2O (10-15), throughout the range of CRS, while median (IQR) driving pressure was 12.3 (10-15) cmH2O and significantly decreased as CRS improved (p<0.001). No differences were found in comorbidities and clinical management between CRS strata. In addition, 28-day ICU mortality and hospital mortality did not differ between CRSgroups.Conclusions This multicentre report provides a comprehensive account of CRS in COVID-19 patients on MV-predominantly males or overweight females, in their late 50s-admitted to ICU during the first international outbreaks. Phenotypes associated with different CRS upon commencement of MV could not be identified.

Neuromuscular blocking agents in critically-ill COVID-19 patients requiring mechanical ventilation

RATIONALE. Neuromuscular blocking agents (NMBA) are used in patients with moderate to severe acute respiratory distress syndrome. NMBA have also been used in COVID-19 patients who required mechanical ventilation (MV), but their benefit-to-risk ratio remains uncertain.METHODS. We investigated the effects associated with the use of NMBA in COVID-19 patients who required MV from January 1, 2020 to October 31, 2020 in 153 hospitals across 6 continents, comprising the COVID-19 Critical Care Consortium. Cox proportional hazards analysis was conducted to study the impact of NMBA on 28-day intensive care unit (ICU) mortality. Hospital/ICU lengths of stay were appraised. We performed a propensity score (PS) matching analysis to control confounding factors.RESULTS. 1227 patients were eligible for analysis, among those 598 (48.7%) received NMBA for 2 days or longer, with a median time from ICU admission to commencement of NMBA therapy of 0 day (IQR 0-1 days). The median duration of NMBA therapy was 2 days (N=789, IQR 1-5). In comparison with standard of care, treatment with NMBA was more frequent in obese (31% vs. 39%, P = 0.03) and diabetic patients (2% vs. 8%, P <0.01) and less frequent in patients with hypertension (52% vs. 46%, P =0.04) or cardiac diseases (21% vs. 14%, P =0.003). Upon commencement of MV, patients who underwent NMBA therapy vs those who did not presented a PaO2/FiO2 of 136.1±69.2 vs. 162.7 ±125.8 (p<0.01), required more often ECMO (10% vs 5.2%, p <0.01) and prone position (25.1% vs 6.2%, p <0.01). Unadjusted 28-day all-cause mortality was similar (58.2% vs. 62.4%, P =0.134) between patients without or with NMBA therapy, respectively, but length of MV (3 days [2-5] vs. 6 [3-12] P <0.01) and ICU stay (8 days [4-14] vs. 13 [7-19] P <0.01) were prolonged. After PS matching, NMBA therapy was strongly associated with 28-day ICU mortality (adjusted HR 3.18, 95% CI 2.65-3.81, P <0.01). CONCLUSION. Use of NMBA in COVID-19 patients requiring MV is associated with increased 28-day mortality, delayed discontinuation of MV and prolonged ICU stay.

Factors associated with mortality in patients with COVID-19 requiring mechanical ventilation: An international cohort study from 139 intensive care unit across 6 continents

Rationale: Patients with COVID-19 commonly develop severe hypoxemic respiratory failure and require invasive mechanical ventilation (MV). The disease burden and predictors of mortality in this population remain uncertain. Methods: Prospective observational cohort study from 139 intensive care units of the international COVID-19 Critical Care Consortium. Patients enrolled from January 14th through November 31st 2020 were included in the analysis. Patient's characteristics and clinical data were assessed. Multivariable Cox proportional hazards analysis was conducted to identify indipendent predictors of mortality within 28 days from commencement of MV. Results: 1578 patients on MV were included into the analysis. Mean±SD age was 59 years±13 and patients were predominantly males (66%). 542 Patients (34.4%) died within 28 days from commencement of MV. Nonsurvivors were slightly older (mean age±SD 62±13 vs. 59±13) and presented more frequently hypertension, chronic cardiac disease and diabetes. Median (IQR) PaO2/FiO2 upon commencement of MV was 96 (68-135) and 111 (81-173) in patients who did not survive vs. survivors, respectively (p=0.04). ECMO (13% vs 25%, p<0.01), inhaled nitric oxide (11% vs 15%, p=0.02) and recruitment manoeauvres (26% vs 31%, p<0.01) were used less frequently in patients who did not survive. Independent risk factors associated with 28-day mortality included age older than 70 years (hazard ratio [HR], 2.83;95% CI, 1.32-6.07), higher creatinine levels upon ICU admission (HR, 1.20;95% CI, 1.03-1.40), and lower pH within 24h from commencement of MV (HR, 0.12;95% CI, 0.02-0.62), while a shorter period (day) from early symptoms to hospitalisation reduced mortality risks (HR, 0.96;95% CI, 0.93-0.99). Conclusions: Our findings from a large international cohort of critically-ill COVID-19 patients on mechanical ventilation emphasises that elderly patients, not promptly admitted to the hospital, and who present higher creatinine levels and acidosis are at higher risk of mortality.

Characteristics and outcomes of patients with COVID-19 admitted to intensive care units-a report from the global COVID-19 critical care consortium

Objective: SARS-CoV-2 has been reported in almost all countries around the world, and a significant proportion of critically ill patients with COVID-19 require care in the intensive care unit (ICU). There have been few observational cohorts including patients in ICU across different countries. We present summary data from a global critical care consortium. Methods: The COVID-19 Critical Care Consortium/ ECMOCARD (COVID-19 CCC/ECMOCARD) is an ongoing international multicenter observational study including more than 377 hospitals in 53 countries. Clinical and treatment characteristics are collected for patients with COVID-19 requiring ICU admission. Results: Data from 2,670 patients with COVID-19 admitted between January 28 and December 19, 2020 were summarized - 182 from Africa, 516 from Asia, 72 from Oceania, 710 from Europe, 343 from Latin America, and 847 from North America. The median (IQR) age was 59 (49 to 68) years, and 909 (34%) were female. 1,283 (49%) patients had hypertension and 830 (32%) had diabetes mellitus. The time from symptom onset to hospital admission was 7 (3 to 10) days, and 1,360 (51%) patients were admitted to ICU on the same day as hospital admission. Upon ICU admission, the heart rate was 95 (80 to 110) beats/min, respiratory rate was 26 (20 to 33) breaths/ min, and oxygen saturation was 93 (89 to 96) %. Details of arterial blood gases and ICU interventions are tabulated. Amongst survivors, ICU length of stay (LOS) was 13 (7 to 25) days, and hospital LOS was 24 (14 to 39) days. As of 31 December 2020, 1,358 (51%) patients were discharged from ICU, and 1,219 (46%) patients survived to hospital discharge. Among 963 (36%) patients who died in hospital, 837 (87%) died within 28 days of ICU admission. Conclusions: The COVID-19 CCC/ECMO offers a unique global perspective of characteristics and outcomes of patients with COVID-19 requiring admission to the ICU.