The Feasibility of Ecmo before Mechanical Ventilation for Severe Respiratory Failure Due to Covid-19

INTRODUCTION: Venovenous extracorporeal membrane oxygenation (VV-ECMO) is typically used to support severe ARDS after the failure of invasive mechanical ventilation (IMV). IMV may cause harm in patients with preexisting barotrauma, shock, or immune compromise. METHOD(S): Single center case-control study of VV-ECMO before IMV (awake ECMO;n=24) compared to conventional ECMO (n=76) after IMV in COVID-19 patients. Groups were compared at baseline before cannulation (awake ECMO) or intubation (conventional ECMO). Propensity matching was performed based on body mass index and injury severity (Simplified Acute Physiology Score II [SAPS II], PaO2:FiO2 ratio). The primary outcome was survival to discharge. Secondary measures of duration of IMV and adverse events were examined. Multivariable adjustments were performed. RESULT(S): Awake ECMO compared to conventional ECMO patients at baseline were more tachypneic (mean +/- standard deviation: 36.3 +/- 9.6 vs 27.4 +/- 7.3;p< 0.0001) with lower SpO2 (median [interquartile range]: 87% [81-92.5] vs 93% [87-96];p=0.01) but similar SAPS II. Fifteen (68%) of awake ECMO patients eventually required IMV. Survival to discharge in awake ECMO trended towards improvement compared to conventional ECMO (70.8% vs. 52.6%;p=0.12). After propensity matching, awake ECMO was associated with increased survival (adjusted odds ratio 6.84 [95% confidence interval 1.08 - 43.38]). Awake ECMO was associated with less duration of IMV before and after propensity matching. Adverse events were similar between groups. CONCLUSION(S): Awake ECMO before IMV is associated with acceptable survival, similar adverse events, and shorter duration of IMV compared to conventional ECMO. This strategy may be preferable in carefully selected patients.

A Single Center Experience with Early Initiation of ECMO Prior to Mechanical Ventilation in COVID-19 Patients with Severe ARDS

Background: Coronavirus disease 2019 (COVID-19) is an ongoing global pandemic that results in a viral pneumonia caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Prognosis is poor among those that develop acute respiratory distress syndrome and progress to mechanical ventilation. Due to the high mortality associated with mechanical ventilation and the unique physiology associated with COVID-19, we compared outcomes in COVID-19 patients placed on ECMO prior to initiation of mechanical ventilation (early group) to patients treated with ECMO after mechanical ventilation (conventional group). Methods: This is a single center retrospective analysis of COVID-19 patients placed on veno-venous (VV) ECMO between 04/06/2020 and 01/15/2021 in a tertiary high-volume ECMO center. Patients between 18 - 70 years of age with a diagnosis of SARS-CoV-2 and diagnosed with ARDS. Patients were considered for ECMO if they had a P/F ratio of less than 50 mmHg for at least three hours, a P/F ratio of less than 80 mmHg for at least 6 hours or an arterial blood pH of less than 7.25 with a pCO2 greater than or equal to 60 mmHg for at least six hours despite optimized ventilator settings (RR> 35 breaths/minute, plateau pressure ≤ 32, tidal volume of 6ml/kg of predicted body weight, FiO2 ≥ 80% and PEEP ≥ 10 cm water). A subset of patients with a rapid deterioration (rapid escalation of O2 requirements, tachypnea RR > 30, tachycardia HR >100) or with clinical signs consistent with poor tolerance to positive pressure ventilation such as a pneumothorax or pneumomediastinum were considered for ECMO prior to mechanical ventilation if they had a P/F <80 despite selfproning with either HFNC 40L/100% in addition to a nonrebreather mask with 15L/100% or non-invasive positive pressure ventilation (NIPPV) with an FiO2 100%. The primary outcome was survival to discharge assessed as a binary outcome of survived or non-survived. Secondary outcomes evaluated included discharge location, length of stay, and incidence of adverse events such as bleeding events, infection, CVA, and pneumothorax requiring chest tube placement. Results: A total of 100 patients were reviewed, including 24 early ECMO patients and 76 conventional ECMO patients. The mean age of the cohort was 48.9 + 11.5 years, 28% were female, and 74% were Hispanic. At baseline, the mean BMI was 31.6 + 5.8, 55% had a history of hypertension, 36% were diabetic and 9% had a history of asthma. Overall, 57% of patients survived to discharge with a median of 23.3 (7.8-40.6) days on ECMO. There were no significant differences in age, gender, BMI, comorbidities, or APACHE scores between the two groups. Prior to ECMO, the early group had lower P/F ratios (52.7 + 11.5 vs. 71.1 + 20.7, p <0.0001), higher pH (7.4 + 0.0 vs. 7.3 + 0.1, p <0.0001), and lower CO2 (36.1 + 6.8 vs 50.9 + 19.1, p <0.0001) than the conventional cohort. Though not significant, there was a trend towards survival in the early ECMO group compared to the conventional group (71% survival vs. 53%, p= .12). Of the early cohort, 15 patients required intubation at some point after cannulation for a median time of 2.5 days (0- 27.0 days). Of the nine patients never intubated, two patients expired, two received a lung transplant, three were discharged home, one discharged to rehab and one to an LTAC facility. There was no difference in adverse events between the two groups. Conclusions: Certain patients with severe ARDS due to COVID-19 may benefit from VV-ECMO cannulation prior to mechanical ventilation with similar outcomes and a trend towards improved mortality.

Comparison of New Viscoelastic Coagulation Monitor with Standard of Care Thromboelastography for Anticoagulation Monitoring during 72-Hour Extracorporeal Life Support

Introduction: Management of coagulation remains the foremost challenge during extracorporeal life support (ECLS). Thromboelastography (TEG) and other viscoelastic clotting tests have shown utility for assessing coagulation status in trauma and ECLS patients and have also been utilized in COVID 19 patients. However, with few exceptions, these methods are performed in a laboratory setting, not at the bedside, and rely on cumbersome, non-portable equipment. The Viscoelastic Coagulation Monitor (VCM;Entegrion;Durham, NC) is a portable device/test developed for use at the bedside and outside hospitals to assess clot formation and lysis using a small sample of whole blood. Blood coagulation is activated by contact with the glass surface on the cartridge, and measurements are derived pertaining to clot formation, stability, and lysis - similar to metrics obtained by the TEG 5000 (Haemonetics;Boston, MA). In a recent study, the relationship of VCM results and heparin dose administered in 36 COVID-19 patients was investigated;however, use of VCM for ECLS with application of heparinase has not been reported. We investigated efficacy of the VCM for coagulation monitoring during 72 hours of continuous ECLS in swine and hypothesized that the VCM with heparinase correlates with TEG heparinase. Methods: Female Yorkshire swine (n=3, 53.4±1.6kg) were anesthetized, mechanically ventilated, and systemically heparinized. Blood samples were collected at baseline, post ECLS, 6, 24, 48, and 72-hours post ECLS initiation. For the VCM, 350μL of whole blood was added to a 0.05 IU heparinase vial, mixed, and then added to a VCM cartridge. For TEG, 340μL of citrated whole blood was added to 20μL 0.2 M CaCl2, and samples were activated with a kaolin reagent. Heparinase cups (Haemonetics;Boston, MA) were used for testing. Spearman correlation was performed to compare standard VCM metrics (clotting time [CT], clot formation time [CFT], alpha, maximum clot firmness [MCF], clot retraction/fibrinolysis [LI30]) to the respective TEG metrics (reaction time [R], clot formation time [K], alpha, maximum amplitude [MA], clot retraction/fibrinolysis [LY30]), and also to other conventional coagulation measurements such as prothrombin time (PT), activated partial thromboplastin time (aPTT), fibrinogen (FIB), and platelet count (PLT) for each timepoint. A p-value of 0.05 was used for significance. Results: All VCM metrics significantly correlated with the respective TEG measurements (see Table 1). Both VCM and TEG show the same positive and negative correlation relationships for clot formation time, clot kinetics, and clot retraction with conventional coagulation tests (see Table 2). Additionally, clotting time and maximum clot firmness did not show moderate or significant correlation with conventional tests. Prothrombin time did not correlate with any values. Conclusion: The VCM is comparable to TEG in assessing coagulation status in heparinized swine and can be used during austere care with ECLS application. In the next round of experiments, we will validate the VCM in clinically-relevant trauma with and without ECLS.

Case Report of a COVID-19 patient treated with Seraph® 100 on Extracorporeal Life Support

Background: The Seraph® 100 Microbind ® Affinity Blood Filter (Seraph ®100) is an extracorporeal broad-spectrum sorbent hemoperfusion filter that removes pathogens and cytokines from the blood and has Emergency Use Authorization (EUA) for the treatment of severe COVID-19. Seraph® 100 can be adapted and primed to a NxStage continuous renal replacement therapy (CRRT) machine and connected to the patient's ECMO circuit. This form of hemofiltration provided a safe and effective approach to decreasing pathogen response within the blood and was tested in our center. Case Review: A 42-year-old male with a past medical history of obesity, hypertension and hypothyroidism was admitted for acute hypoxemic respiratory failure secondary to COVID-19. His 65 day ECMO course was complicated by encephalopathy, right heart dysfunction, severe epistaxis, esophageal ulcers and enterococcus faecalis bacteremia. On ECMO day 16, the patient became febrile, C-reactive protein increased to 215 mg/L and he became hypotensive. In addition to appropriate antibiotics, the multidisciplinary team decided to initiate Seraph® 100 for the E.faecalis bacteremia. The filter was adapted and primed into the NxStage machine by the nurse caring for the patient. The NxStage lines were then connected to the ECMO circuit via pigtail connections. The blood was cycled from the post-oxygenator pigtail to the NxStage and returned to the pre-oxygenator pigtail on the ECMO circuit. The target time for continuous Seraph® 100 therapy is between 24-48 hours. Cultures were collected from the NxStage line pre-filter and again, six hours later, from a port post-filter. The pre-filter cultures came back positive for E.faecalis and the post-filter cultures were negative. Additional blood cultures collected the following day remained negative. The patient's condition improved rapidly and allowed him to begin physical therapy and reduce ventilator support over the next 48 days on ECMO. He was discharged from the hospital to rehab for two weeks before going home. Discussion: Introduction of hemofiltration by Exthera provided an additional therapy that has proven to be effective in the reduction of sepsis causing pathogens when used in conjunction with conventional care for patients with COVID-19 suffering from bacteremia. In this case, incorporating hemofiltration via the ECMO circuit showed no increase in undue risk to the patient with an efficacy in decreasing bacteremia, contributing to the survival of the patient.

Diagnosis and Treatment of TBI and Polytrauma during Ground and High-Altitude Evacuation using Liquid Biopsy and Extracorporeal Life Support

TBI alone and in combination with polytrauma and lung injury caused up to 83 percent of nonsurvivable combat-related deaths. There is no accurate diagnosis method or viable therapeutic intervention for these casualties primarily due to the severity of injury, which can be unrecognized early on. Our proposal will address these unmet needs via utilization of a model of TBI with targeted descriptors of injury severity derived from bedside cell free DNA (cfDNA) testing, and then via addition of polytrauma and lung injury with subsequent testing of therapeutic intervention via extracorporeal life support (ECLS).