Perfusion

During extracorporeal membrane oxygenation, the large contact surface between the blood and the extracorporeal circuit causes a continuous activation of coagulation and inflammation. Unfractionated heparin, a glycosaminoglycan that must bind to antithrombin as a cofactor, is currently the standard anticoagulant adopted during extracorporeal membrane oxygenation. Antithrombin, beyond being a potent natural anticoagulant, acts in the cross-talk between coagulation and inflammatory system through anticoagulation and coagulation-independent effects.

In this review, we describe, in the adult setting of veno-venous extracorporeal membrane oxygenation, the pathophysiological rationale for antithrombin use, the current practice of administration, and the effects of antithrombin on anticoagulation, bleeding, and outcomes.

Studies on adults (18 years or older) on veno-venous extracorporeal membrane oxygenation published from 1995 to 2018 in order to evaluate the use of antithrombin.

In adults on veno-venous extracorporeal membrane oxygenation, antithrombin supplementation has a highly pathophysiological rationale since coagulation factor consumption, systemic inflammatory response syndrome, and endothelial activation are triggered by extracorporeal membrane oxygenation. Eleven articles are focused on the topic but among the authors there is no consensus on the threshold for supplementation (ranging from 70% to 80%) as well as on the dose (rarely standardized) and time of administration (bolus vs continuous infusion). Consistently, antithrombin is considered able to achieve better anticoagulation targets in or not in the presence of heparin resistance. The impact of antithrombin administration on bleeding still shows contrasting results.

Antithrombin use in veno-venous extracorporeal membrane oxygenation should be investigated on the threshold for supplementation, dose, and time of administration.

Veno-arterial extracorporeal membrane oxygenation may be used to support patients with refractory cardiogenic shock. Many patients can be successfully weaned, the ability of some medications to facilitate weaning from veno-arterial extracorporeal membrane oxygenation were reported. To date, there are limited studies investigating the impact of levosimendan on veno-arterial extracorporeal membrane oxygenation weaning. The objective of this systematic review and meta-analysis was to assess the effects of levosimendan on successful weaning from veno-arterial extracorporeal membrane oxygenation and survival in adult patients with cardiogenic shock.

We performed a systematic review and meta-analysis (PubMed, the Cochrane Library, and the International Clinical Trials Registry Platform published from the year 2000 onwards) investigating whether levosimendan offers advantages compared to standard therapy or placebo, in cardiogenic shock adult patients treated with veno-arterial extracorporeal membrane oxygenation. The primary outcome was veno-arterial extracorporeal membrane oxygenation successful weaning, whereas secondary outcome was all-cause mortality at the longest follow-up available. We pooled risk ratio and 95% confidence interval using fixed and random effects models according to the heterogeneity.

A total of five non-randomized clinical trials comprising 557 patients were included, 299 patients for levosimendan and 258 patients for control groups. The pooled prevalence of veno-arterial extracorporeal membrane oxygenation successful weaning was 61.4% (95% confidence interval 39.8-82.9%), and all-cause mortality was 36% (95% confidence interval 29.6-48.8%). There was a significant increase in veno-arterial extracorporeal membrane oxygenation successful weaning with levosimendan compared to the controls (risk ratio = 1.42 (95% confidence interval 1.12-1.8), p for effect = 0.004, I² = 71%). A decrease risk of all-cause mortality in the levosimendan group was also observed, risk ratio = 0.62 (95% confidence interval 0.44-0.88), p for effect = 0.007, I² = 36%.

The use of levosimendan on adult patients with cardiogenic shock may facilitate the veno-arterial extracorporeal membrane oxygenation weaning and reduce all-cause mortality. Few articles of this topic are available, and prospective, randomized multi-center trials are warranted to conclude decisively on the benefits of levosimendan in this setting.

Extracorporeal carbon dioxide removal means the removal of carbon dioxide from the blood across a gas exchange membrane without substantially improving oxygenation. Carbon dioxide removal is possible with substantially less extracorporeal blood flow than needed for oxygenation. Techniques for extracorporeal carbon dioxide removal include (1) pumpless arterio-venous circuits, (2) low-flow venovenous circuits based on the technology of continuous renal replacement therapy, and (3) venovenous circuits based on extracorporeal membrane oxygenation technology.

Extracorporeal carbon dioxide removal has been shown to enable more protective ventilation in acute respiratory distress syndrome patients, even beyond the so-called “protective” level. Although experimental data suggest a benefit on ventilator induced lung injury, no hard clinical evidence with respect to improved outcome exists. In addition, extracorporeal carbon dioxide removal is a tool to avoid intubation and mechanical ventilation in patients with acute exacerbated chronic obstructive pulmonary disease failing non-invasive ventilation. This concept has been shown to be effective in 56-90% of patients. Extracorporeal carbon dioxide removal has also been used in ventilated patients with hypercapnic respiratory failure to correct acidosis, unload respiratory muscle burden, and facilitate weaning. In patients suffering from terminal fibrosis awaiting lung transplantation, extracorporeal carbon dioxide removal is able to correct acidosis and enable spontaneous breathing during bridging. Keeping these patients awake, ambulatory, and breathing spontaneously is associated with favorable outcome.

Complications of extracorporeal carbon dioxide removal are mostly associated with vascular access and deranged hemostasis leading to bleeding. Although the spectrum of complications may differ, no technology offers advantages with respect to rate and severity of complications. So called “high-extraction systems” working with higher blood flows and larger membranes may be more effective with respect to clinical goals.

Methylprednisolone has been used for acute respiratory distress syndrome with variable results. Veno-venous extracorporeal membrane oxygenation use in acute respiratory distress syndrome has increased. Occasionally, both are used. We hypothesized that methylprednisolone could improve lung compliance and ease weaning from extracorporeal membrane oxygenation in acute respiratory distress syndrome patients.

We retrospectively reviewed all patients in our veno-venous extracorporeal membrane oxygenation unit treated with methylprednisolone over a 20 month period. Methylprednisolone was initiated for inability to wean off veno-venous extracorporeal membrane oxygenation. Dynamic compliance (Cdyn) was calculated at cannulation, methylprednisolone initiation, and decannulation. Demographics, extracorporeal membrane oxygenation–specific data, and ventilator data were collected. Wilcoxon rank-sum test was used to test for differences in dynamic compliance.

A total of 12 veno-venous extracorporeal membrane oxygenation patients received methylprednisolone. Mean age was 50 (±15) years. Seven had influenza. Methylprednisolone was started on median Day 16 (interquartile range: 11-22) of veno-venous extracorporeal membrane oxygenation. In total, 10 patients had veno-venous extracorporeal membrane oxygenation decannulation on median Day 12 (7-22) after methylprednisolone initiation. Two patients died before decannulation. The 10 decannulated patients had initial median dynamic compliance (mL × cm H₂O⁻¹) of 12 (7-23), then 16 (10-24) at methylprednisolone initiation, and then 44 (34-60) at decannulation. Dynamic compliance was higher at decannulation than methylprednisolone initiation (p = 0.002), and unchanged from cannulation to methylprednisolone initiation for all patients (p = 0.97). A total of 10 patients had significant infections. None had significant gastrointestinal bleed or wound healing issues.

Methylprednisolone may be associated with improved compliance in acute respiratory distress syndrome allowing for decannulation from veno-venous extracorporeal membrane oxygenation. High rates of infection are associated with methylprednisolone use in veno-venous extracorporeal membrane oxygenation. Further studies are required to identify appropriate patient selection for methylprednisolone use in patients on veno-venous extracorporeal membrane oxygenation.

To determine the oxygenator impact on alterations of voriconazole in a contemporary neonatal/pediatric (1/4 inch) and adolescent/adult (3/8 inch) extracorporeal membrane oxygenation circuit including the Quadrox-i^® oxygenator.

Simulated closed-loop extracorporeal membrane oxygenation circuits (1/4 and 3/8 inch) were prepared with a Quadrox-i pediatric and Quadrox-i adult oxygenator and blood primed. In addition, 1/4- and 3/8-inch circuits were also prepared without an oxygenator in series. A one-time dose of voriconazole was administered into the circuits, and serial pre- and post-oxygenator concentrations were obtained at 5 minutes, 1, 2, 3, 4, 5, 6, and 24 hour time points. Voriconazole was also maintained in a glass vial and samples were taken from the vial at the same time periods for control purposes to assess for spontaneous drug degradation

For the 1/4-inch circuit, there was an approximate mean of 64-67% voriconazole loss with the oxygenator in series and mean of 15-20% voriconazole loss without an oxygenator in series at 24 hours. For the 3/8-inch circuit, there was an approximate mean of 44-51% voriconazole loss with the oxygenator in series and a mean of 8-12% voriconazole loss without an oxygenator in series at 24 hours. The reference voriconazole concentrations remained relatively constant during the entire study period demonstrating that the drug loss in each size of the extracorporeal membrane oxygenation circuit with or without an oxygenator was not a result of spontaneous drug degradation.

This ex vivo investigation demonstrated substantial voriconazole loss within an extracorporeal membrane oxygenation circuit with an oxygenator in series with both sizes of the Quadrox-i oxygenator at 24 hours and no significant voriconazole loss in the absence of an oxygenator. Further evaluations with multiple dose in vitro and in vivo investigations are needed before specific voriconazole dosing recommendations can be made for clinical application with extracorporeal membrane oxygenation.

Agitation and delirium in critically ill patients after cardiac surgery carry poor in-hospital prognosis. Identifying risk factors may promote its prevention and management. Accordingly, this study aimed to evaluate the incidence of agitation and hyperactive delirium in postcardiotomy patients during the extracorporeal membrane oxygenation support and to identify the risk factors for its development.

This single center, retrospective study was conducted at Beijing Anzhen Hospital, Capital Medical University. Data were extracted from the prospective institutional registry database of extracorporeal membrane oxygenation patients. Univariate and multivariate logistic regression analyses were performed to predict risk factors.

A total of 170 consecutive adult patients underwent extracorporeal membrane oxygenation in our hospital from January 2016 to December 2017. Ninety-four patients were included in the final analysis. The incidence of agitation and hyperactive delirium was 35% in our population of extracorporeal membrane oxygenation–supported postcardiotomy patients. Agitation and delirium usually occurred within the first 3 days of extracorporeal membrane oxygenation. Multivariable analysis showed that history of previous stroke (without preoperative cognitive dysfunction; odds ratio, 4.425, 95% confidence interval: 1.171-16.716; p = 0.028) and mean arterial pressure reduction (before extracorporeal membrane oxygenation initiation) ⩾ 49 mmHg (odds ratio, 7.570, 95% confidence interval: 2.366-24.219, p = 0.001) were independent risk factors for agitation and hyperactive delirium during extracorporeal membrane oxygenation support. The areas under the receiver operating characteristic curve for the prediction of agitation and hyperactive delirium was 0.704 (95% confidence interval 0.589-0.820, p = 0.001). There was more severe arrhythmia in the agitation patients.

Our results suggest that the prevalence of agitation and hyperactive delirium in postcardiotomy patients with extracorporeal membrane oxygenation support is high. In addition, previous stroke and severe mean arterial pressure reduction before extracorporeal membrane oxygenation initiation is predictive of agitation and hyperactive delirium.

Antineutrophil cytoplasmic autoantibody–associated vasculitis is an immune-mediated necrotizing vasculitis, affecting small- and medium-sized vessels.

A 22-year-old female patient with free medical history presented with life-threatening pulmonary hemorrhage due to antineutrophil cytoplasmic autoantibody–associated vasculitis, temporarily associated with influenza A H1N1 infection. Due to rapidly worsening respiratory failure, despite conventional management, veno-venous peripheral extracorporeal membrane oxygenation was initiated and continued for 26 days, with subsequent renal replacement therapy.

We present a case of severe antineutrophil cytoplasmic autoantibody–associated pulmonary vasculitis, managed with veno-venous extracorporeal membrane oxygenation at the initial phase. Despite the significant challenges raised with the use of extracorporeal membrane oxygenation in pulmonary hemorrhage cases, extracorporeal membrane oxygenation may have a significant impact on outcome in this setting, by providing adequate time for a successful immunosuppressive treatment.

The SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) coronavirus has emerged as a highly contagious respiratory pathogen causing severe acute lung injury. Extracorporeal membrane oxygenation is a standard tool for the management of life-threatening acute respiratory distress syndrome, but the use of this resource-intensive therapy has come into question due to strained medical systems and limited proven treatments for COVID-19.

A 16-year-old female with obesity presented with fever, myalgias, cough, and tachypnea and was diagnosed with COVID-19. She progressed to severe pediatric acute respiratory distress syndrome requiring intubation on hospital day 4 and cannulation to veno-venous extracorporeal membrane oxygenation on hospital day 6. The patient received remdesivir, steroids, and anakinra. The patient was successfully decannulated on hospital day 12 and was discharged home on hospital day 21.

We report the use of veno-venous extracorporeal membrane oxygenation as a bridge to lung recovery in a pediatric patient with severe pediatric acute respiratory distress syndrome due to COVID-19.