Reducing Broad-Spectrum Antimicrobial Use in Extracorporeal Membrane Oxygenation: Reduce AMMO Study.

BACKGROUND: The use of extracorporeal membrane oxygenation (ECMO) in critically ill adults is increasing. There are currently no guidelines for antimicrobial prophylaxis. We analyzed 7 years of prophylactic antimicrobial use across 3 time series for patients on ECMO at our institution in the development, improvement, and streamlining of our ECMO antimicrobial prophylaxis protocol. METHODS: In this quasi-experimental interrupted time series analysis, we evaluated the impact of an initial ECMO antimicrobial prophylaxis protocol, implemented in 2014, on antimicrobial use and National Healthcare Safety Network-reportable infection rates. Then, following a revision and streamlining of the protocol in November 2018, we reevaluated the same metrics. RESULTS: Our study population included 338 intensive care unit patients who received ECMO between July 2011 and November 2019. After implementation of the first version of the protocol, we did not observe significant changes in antimicrobial use or infection rates in these patients; however, following revision and streamlining of the protocol, we demonstrated a significant reduction in broad-spectrum antimicrobial use for prophylaxis in patients on ECMO without any evidence of a compensatory increase in infection rates. CONCLUSIONS: Our final protocol significantly reduces broad-spectrum antimicrobial use for prophylaxis in patients on ECMO. We propose a standard antimicrobial prophylaxis regimen for patients on ECMO based on current evidence and our experience.Summary: There are no guidelines for antimicrobial prophylaxis in patients on extracorporeal membrane oxygenation (ECMO). A rational approach employing concepts of antimicrobial stewardship can drive logical antimicrobial selection for prophylaxis in patients on ECMO without adversely impacting outcomes.

Comparison of Bivalirudin Versus Heparin for Maintenance Systemic Anticoagulation During Adult and Pediatric Extracorporeal Membrane Oxygenation.

OBJECTIVES: To provide a comparative analysis of conventional heparin-versus bivalirudin-based systemic anticoagulation in adult and pediatric patients supported on extracorporeal membrane oxygenation. DESIGN: Retrospective chart review study of adult and pediatric patients receiving extracorporeal membrane oxygenation from January 1, 2014, to October 1, 2019. SETTING: A large, high-volume tertiary referral adult and pediatric extracorporeal membrane oxygenation center. PATIENTS: Four hundred twenty-four individuals requiring extracorporeal membrane oxygenation support and systemically anticoagulated with either unfractionated heparin (223 adult and 65 pediatric patients) or bivalirudin (110 adult and 24 pediatric patients) were included. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Digital data abstraction was used to retrospectively collect patient details. The majority of both groups were cannulated centrally (67%), and the extracorporeal membrane oxygenation type was predominantly venoarterial (84%). The adult bivalirudin group had a greater occurrence of heparin-induced thrombocytopenia (12% vs 1%; p < 0.01) and was more likely to require postcardiotomy extracorporeal membrane oxygenation (36% vs 55%; p < 0.01). There were no statistical differences between the groups in regards to age, sex, and extracorporeal membrane oxygenation initiation location. The main finding was a reduced mortality in the adult bivalirudin group (odds ratio, 0.39; p < 0.01), whereas no difference was noted in the pediatric group. A significant reduction in the composite transfusion requirement in the first 24 hours was noted in the pediatric bivaluridin group with an odds ratio of 0.28 (p = 0.02). Groups did not differ in regard to laboratories per day, anticoagulant dose adjustments, or ischemic complications. CONCLUSIONS: When compared with heparin-based systemic anticoagulation, bivalirudin demonstrated feasibility and safety as established by the absence of increases in identifiable adverse outcomes while manifesting substantial improvements in hospital mortality in adult patients. Further studies are necessary to corroborate these findings and further elucidate the role of bivalirudin during extracorporeal membrane oxygenation support.

Epidemiology of Acute Respiratory Distress Syndrome Following Hematopoietic Stem Cell Transplantation.

OBJECTIVES: Pulmonary complications are common following hematopoietic stem cell transplantation. Numerous idiopathic post-transplantation pulmonary syndromes have been described. Patients at the severe end of this spectrum may present with hypoxemic respiratory failure and pulmonary infiltrates, meeting criteria for acute respiratory distress syndrome. The incidence and outcomes of acute respiratory distress syndrome in this setting are poorly characterized. DESIGN: Retrospective cohort study. SETTING: Mayo Clinic, Rochester, MN. PATIENTS: Patients undergoing autologous and allogeneic hematopoietic stem cell transplantation between January 1, 2005, and December 31, 2012. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Patients were screened for acute respiratory distress syndrome development within 1 year of hematopoietic stem cell transplantation. Acute respiratory distress syndrome adjudication was performed in accordance with the 2012 Berlin criteria. In total, 133 cases of acute respiratory distress syndrome developed in 2,635 patients undergoing hematopoietic stem cell transplantation (5.0%). Acute respiratory distress syndrome developed in 75 patients (15.6%) undergoing allogeneic hematopoietic stem cell transplantation and 58 patients (2.7%) undergoing autologous hematopoietic stem cell transplantation. Median time to acute respiratory distress syndrome development was 55.4 days (interquartile range, 15.1-139 d) in allogeneic hematopoietic stem cell transplantation and 14.2 days (interquartile range, 10.5-124 d) in autologous hematopoietic stem cell transplantation. Twenty-eight-day mortality was 46.6%. At 12 months following hematopoietic stem cell transplantation, 89 patients (66.9%) who developed acute respiratory distress syndrome had died. Only 7 of 133 acute respiratory distress syndrome cases met criteria for engraftment syndrome and 15 for diffuse alveolar hemorrhage. CONCLUSIONS: Acute respiratory distress syndrome is a frequent complication following hematopoietic stem cell transplantation, dramatically influencing patient-important outcomes. Most cases of acute respiratory distress syndrome following hematopoietic stem cell transplantation do not meet criteria for a more specific post-transplantation pulmonary syndrome. These findings highlight the need to better understand the risk factors underlying acute respiratory distress syndrome in this population, thereby facilitating the development of effective prevention strategies.

Extracorporeal membrane oxygenation and acute kidney injury: a single-center retrospective cohort.

To assess the relationship between acute kidney injury (AKI) with outcomes among patients requiring extracorporeal membrane oxygenation (ECMO). This is a single-center, retrospective cohort study of adult patients admitted to intensive care units (ICU) at a tertiary referral hospital requiring ECMO from July 1, 2015, to August 30, 2019. We assessed the temporal relationship of AKI and renal replacement therapy with ECMO type (VV vs. VA). The primary outcome was in-hospital mortality rates. We used Kruskal-Wallis or chi-square tests for pairwise comparisons, cause-specific Cox proportional hazards models were utilized for the association between AKI prevalence and in-hospital mortality, and a time-dependent Cox model was used to describe the association between AKI incidence and mortality. After the screening, 190 patients met eligibility criteria [133 (70%) AKI, 81 (43%) required RRT]. The median age was 61 years, and 61% were males. Among AKI patients, 48 (36%) and 85 (64%) patients developed AKI before and after ECMO, respectively. The SOFA Day 1, baseline creatinine, respiratory rate (RR), use of vasopressin, vancomycin, proton pump inhibitor, antibiotics, duration of mechanical ventilation and ECMO, and ICU length of stay were higher in AKI patients compared with those without AKI (P < 0.01). While ICU and in-hospital mortality rates were 46% and 50%, respectively, there were no differences based on the AKI status. The type and characteristics of ECMO support were not associated with AKI risk. Among AKI patients, 77 (58%) were oliguric, and 46 (60%) of them received diuretics. Urine output in the diuretic group was only higher on the first day than in those who did not receive diuretics (P = 0.03). Among ECMO patients, AKI was not associated with increased mortality but was associated with prolonged duration of mechanical ventilation and ICU length of stay.

Increasing Mortality in Venovenous Extracorporeal Membrane Oxygenation for COVID-19-Associated Acute Respiratory Distress Syndrome.

OBJECTIVES: Determine the factors associated with mortality in venovenous extracorporeal membrane oxygenation (V-V ECMO) patients with COVID-19 infection and provide an updated report of clinical outcomes for patients treated with V-V ECMO for COVID-19 in Minnesota. DESIGN: Multicenter prospective observational study. SETTING: The four adult Extracorporeal Life Support Organization-certified Centers of Excellence in Minnesota. PATIENTS: A total of 100 patients treated with V-V ECMO for COVID-19-associated acute respiratory distress syndrome (ARDS) from March 2020 to May 2021. INTERVENTIONS: Not applicable. MEASUREMENTS AND MAIN RESULTS: The primary outcome was 60-day survival for patients treated with V-V ECMO for COVID-19. Outcomes of patients treated from November 2020 to May 2021(cohort 2) were compared with data from a previous cohort of patients, collected from March 2020 to October 2020 (cohort 1). The data from both cohorts were merged into a single dataset (Combined Cohort). Survival on V-V ECMO due to COVID-19-associated ARDS significantly decreased after October 2020 (63% vs 41%; p = 0.026). The median interval from hospital admission to V-V ECMO cannulation was significantly associated with 60-day mortality (10 d [6-14 d] in nonsurvivors vs 7 d [4-9 d] in survivors; p = 0.001) in the Combined Cohort and was also significantly longer in cohort 2 than cohort 1 (10 d [7-14 d] vs 6 d [4-10 d]; p < 0.001). In the Combined Cohort, the 60-day survival for patients who did not receive steroids was 86% (n = 12) versus 45% (n = 39) for patients who received at least one dose of steroids (p = 0.005). CONCLUSIONS: There was a significant increase in mortality for patients treated with V-V ECMO for COVID-19-associated ARDS in cohort 2 compared with cohort 1. Further research is required to determine the cause of the worsening trend in mortality.

The Impact of a Standardized Refractory Hypoxemia Protocol on Outcome of Subjects Receiving Venovenous Extracorporeal Membrane Oxygenation.

BACKGROUND: Current mechanical ventilation practice and the use of treatment adjuncts in patients requiring extracorporeal membrane oxygenation (ECMO) for refractory hypoxemia (RH) vary widely and their impact on outcomes remains unclear. In 2015, we implemented a standardized approach to protocolized ventilator settings and guide the escalation of adjunct therapies in patients with RH. This study aimed to investigate ICU mortality, its associated risk factors, and mechanical ventilation practice before and after the implementation of a standardized RH guideline in patients requiring venovenous ECMO (VV-ECMO). METHODS: This was a single-center, retrospective cohort study of patients undergoing VV-ECMO due to RH respiratory failure between January 2008 and March 2015 (before RH protocol implementation) and between April 2015 and October 2019 (after RH protocol implementation). RESULTS: A total of 103 subjects receiving VV-ECMO for RH were analyzed. After implementation of the RH protocol, more subjects received prone positioning (6.7% vs 23.3%, P = .02), and fewer received high-frequency oscillatory ventilation than before launching the RH protocol (0% vs 13.3%, P = .01). Plateau pressure was also lower before initiation of ECMO (P = .04) and at day 1 during ECMO (P = .045). Driving pressure was consistently lower at days 1, 2, and 3 after ECMO initiation: median 13.0 (interquartile range [IQR] 10.6-18.0) vs 16.0 (IQR 14.0-20.0) cm H2O at day 1 (P = .003); 13.0 (IQR 11.0-15.9) vs 15.5 (IQR 12.0-20.0) cm H2O at day 2 (P = .03); and 12.0 (IQR 10.0-14.5) vs 15.0 (IQR 12.0-19.0) cm H2O at day 3 (P = .005). CONCLUSIONS: The implementation of a standardized RH guideline improved compliance with a lung-protective ventilation strategy and utilization of the prone position and was associated with lower driving pressure during the first 3 days after ECMO initiation in subjects with refractory hypoxemia.

The Use of Venovenous Extracorporeal Membrane Oxygenation in COVID-19 Infection: One Region's Comprehensive Experience.

Severe acute respiratory distress syndrome (ARDS) unresponsive to conventional intensive care unit (ICU) management is an accepted indication for venovenous extracorporeal membrane oxygenation (V-V ECMO) support. The frequency with which patients with coronavirus disease 2019 (COVID-19) pneumonia are selected for V-V ECMO has not been described. This was a cohort study including all patients placed on either V-V ECMO or venoarteriovenous ECMO at the four adult ECMO Centers of Excellence. Primary outcomes evaluated were survival to decannulation from the ECMO circuit, survival to discharge, and 60-day survival. Secondary outcomes were hospital length of stay (LOS), ICU LOS, length of ECMO cannulation, and length of intubation. During the study period, which corresponded to the first surge in COVID-19 hospitalizations in Minnesota, 35 patients with ARDS were selected for V-V ECMO support out of 1,849 adult ICU patients with COVID-19 infection in the state (1.9% incidence; 95% CI, 1.3-2.6%). This represents 46 (95% CI, 34-61) expected V-V ECMO patients per 100,000 confirmed positive cases of COVID-19. Twenty-six of the 35 patients (74.3%) supported with V-V ECMO survived to 60-day post-ECMO decannulation. Recent studies have demonstrated ongoing success rescuing patients with severe ARDS in COVID-19 infection. Our data add to the support of ECMO and the consideration for encouraging cooperation among regional ECMO centers to ensure access to this highest level of care. Finally, by evaluating all the patients of a single region, we estimate overall need for this resource intensive intervention based on the overall number of COVID-19 cases and ICU admissions.

Risk Factors of Mortality for Patients Receiving Venovenous Extracorporeal Membrane Oxygenation for COVID-19 Acute Respiratory Distress Syndrome.

Background: Venovenous extracorporeal membrane oxygenation (VV-ECMO) for select adults with severe acute respiratory distress syndrome (ARDS) cause by coronavirus disease 2019 (COVID-19) infection is a guideline-supported therapy with associated hospital survival of 62%-74%, similar to expected survival with VV-ECMO for other indications. However, ECMO is a resource-heavy intervention, and these patients often require long ECMO runs and prolonged intensive care unit (ICU) care. Identifying factors associated with mortality in VV-ECMO patients with COVID-19 infection can inform the evaluation of ECMO candidates as well as prognostication for those patients on prolonged VV-ECMO. Patients and Methods: This was a retrospective cohort study that included all patients who received either VV- or venoarteriovenous (VAV)-ECMO at one of four ECMO Centers of Excellence in the state of Minnesota between March 1, 2020 and November 1, 2020. The primary outcome was 60-day survival. Secondary outcomes were hospital complications, infectious complications, and complications from ECMO. Results: There were 46 patients who met criteria during this study period and 30 survived to 60-day follow-up (65.2%). Prior to cannulation, older patient age (55.5 in non-survivors vs. 49.1 years in survivors; p = 0.03), lower P/F ratio (62.1 vs. 76.2; p = 0.04), and higher sequential organ failure assessment (SOFA) score (8.1 vs. 6.6; p = 0.02) were identified as risk factors for mortality. After ECMO cannulation, increased mortality was associated with increased number of antibiotic days (25.9 vs. 14.5; p = 0.04), increased number of transfusions (23.9 vs. 9.9; p = 0.03), elevated white blood cell (WBC) count at post-ECMO days one through three, elevated D-dimer at post-ECMO day 21-27, and decreased platelet count from post-ECMO days 14 and onward using univariable analysis. Conclusions: Multiple markers of infection including leukocytosis, thrombocytopenia, and increased antibiotic days are associated with increased mortality in patients placed on VV-ECMO for COVID-19 infection and subsequent ARDS. Knowledge of these factors may assist with determining appropriate candidates for this limited resource as well as direct goals of care in prolonged ECMO courses.

A Systematic Review of Preexisting Sepsis and Extracorporeal Membrane Oxygenation.

We retrospectively reviewed all pertinent extracorporeal membrane oxygenation (ECMO) studies (January 1995 to September 2017) of adults with sepsis as a primary indication for intervention and its association with morbidity and mortality. Collected data included study type, ECMO configuration, outcomes, effect size, and other features. Advanced age was a risk factor for death. Compared with nonsurvivors, survivors had a lower median Sepsis-Related Organ Failure Assessment score on day 3 (15 vs. 18, p = 0.01). Biomarkers in survivors and nonsurvivors, respectively, were peak lactate (from two studies: 4.5 vs. 15.1 mmol/L, p = 0.03; 3.6 ± 3.7 vs. 3.3 ± 2.4 mmol/L, p = 0.850) and procalcitonin levels (41 vs. 164 ng/ml, p = 0.008). Bacteremia was associated with catheter colonization, and 90.5% of a group without bloodstream infections survived to discharge; ECMO weaning was possible for less than half the bloodstream infection group. Myocarditis portended favorable outcomes for patients with sepsis who received ECMO. Extracorporeal membrane oxygenation was used in immunosuppressed patients with refractory cardiopulmonary insufficiency from severe sepsis with successful weaning from ECMO for most patients. Overall survival varied substantially among studies (15.38-71.43%). Existing studies do not present well-defined patterns supporting use of ECMO in sepsis because of sample sizes and disparate study designs.

Dual RVAD-ECMO Circuits to Treat Cardiogenic Shock and Hypoxemia Due to Necrotizing Lung Infection: A Case Report.

Utilization of venoarterial extracorporeal membrane oxygenation (VA-ECMO) is expanding, but dual VA-ECMO circuits to treat cardiogenic shock with refractory hypoxemia is unreported. We describe the case of combined cardiogenic and distributive shock due to necrotizing pulmonary blastomycosis. After initial central VA-ECMO cannulation, acute respiratory distress syndrome (ARDS) with increasing shunt resulted in significant central hypoxemia due to progressive ventilation-perfusion mismatch. An additional circuit provided complete oxygenation of the high circulating volume. After 4 months on support, he underwent successful heart-lung-kidney transplantation. Dual ECMO circuits are technically feasible and may be advantageous in specific circumstances of high pulmonary shunting resulting in excessive hypoxemia unbalanced with appropriate oxygen delivery.

The Clinical Effect of an Early, Protocolized Approach to Mechanical Ventilation for Severe and Refractory Hypoxemia.

BACKGROUND: ARDS remains a source of significant morbidity and mortality in the critically ill patient. The mainstay of therapy entails invasive mechanical ventilation utilizing a lung-protective strategy designed to limit lung injury associated with excessive stress and strain while the underlying etiology of respiratory failure is identified and treated. Less is understood about what to do once conventional ventilation parameters have been optimized but the patient's respiratory status remains unchanged or worsens. In 2015, a protocolized, stepwise approach to mechanical ventilation with partially automated and clearly defined thresholds for management changes was implemented at our institution. We hypothesized that, by identifying appropriate patients earlier, time-to-escalation and rescue therapy implementation would be shortened. METHODS: Subjects with severe ARDS, treated with prone positioning based on our institution's protocolized approach from December 2013 to August 2016 were included. Their baseline characteristics, severity of illness scores, and mechanical ventilation parameters were collected and analyzed. RESULTS: Baseline characteristics, tidal volumes, PaO2 /FIO2 , duration of ventilation after proning, and mortality were similar in both groups. Median (interquartile range [IQR]) PEEP at the time of proning was higher after the protocol implementation (12.5 cm H2O [IQR 6.5-19.4] vs 18 cm H2O [IQR 10-22], P = .386), and mean (IQR) respiratory system driving pressure was lower (16 cm H2O [IQR 13-36.2] vs 12 cm H2O [IQR 9-19.6], P = .029). Median (IQR) time from refractory hypoxemia identification to proning was shorter after protocol implementation (42.2 h [IQR 6.83-347.2] vs 16.3 h [IQR 1-99.7], I = .02), and PaO2 /FIO2 at 1 h after proning was higher. ICU and hospital LOS were shorter after the protocol implementation. CONCLUSIONS: Following the implementation of an early, evidence-based, protocolized approach to optimizing mechanical ventilation, subjects with true refractory hypoxemia were identified earlier and time to proning was significantly shorter. Despite improvement in the evaluation and management of refractory hypoxemia as well as time to initiation of prone positioning, mortality was unchanged and there was variation in the duration of the position.

Practical Implementation of Failure Mode and Effects Analysis for Extracorporeal Membrane Oxygenation Activation.

Extracorporeal membrane oxygenation (ECMO) is used to treat severe hypoxemic respiratory failure and as a rescue therapy for patients with cardiopulmonary arrest within a narrow window of time. A failure modes and effects analysis (FMEA) was conducted to analyze the clinical and operational processes leading to delays in initiating ECMO. FMEA determined these highest-risk failure modes that were contributing to process failure: (1) ECMO candidacy not determined in time, (2) no or incomplete evaluation for ECMO prior to consult or arrest, (3) ECMO team not immediately available, and (4) cannulation not completed in time. When implemented collectively, a total of 4 interventions addressed more than 95% of the system failures. These interventions were (1) ECMO response pager held by a team required for decision, (2) distribution of institutionally defined inclusion/exclusion criteria, (3) educational training for clinicians consulting the ECMO team, and (4) establishment of a mobile ECMO insertion cart.

Successful Treatment of Refractory Hypoxemia Secondary to Disseminated Histoplasmosis Using Extracorporeal Membrane Oxygenation Support.

Refractory hypoxemia secondary to acute respiratory distress syndrome (ARDS) is associated with high mortality. Extracorporeal membraneoxygenation (ECMO) is an accepted strategy for treating refractory hypoxemia in patients with ARDS but is relatively contraindicated in the setting of systemic infections. We present a case of successful ECMO use in a host with refractory hypoxemia secondary to disseminated histoplasmosis with fungemia and discuss our management approach to this difficult patient.