After ECMO Decannulation, Are Patients Thriving or Just Surviving?

The use of extracorporeal membrane oxygenation (ECMO) to support patients with cardiac arrest, cardiogenic shock, and acute respiratory distress syndrome is rising worldwide.1 While ECMO may save the lives of some of our sickest patients, the outlook of ECMO survivorship remains uncertain. Defining longer-term functional and neuropsychiatric outcomes in ECMO survivors is important for 3 reasons. First, critically ill patients are at high risk of experiencing postintensive care syndrome (PICS), defined as new physical, cognitive, or psychological impairments that present in survivors of critical illness after hospital discharge.2 PICS is associated with more severe illness and longer intensive care unit length of stay.3 Because ECMO is reserved for patients with refractory shock or hypoxia, patients treated with ECMO represent a severely ill patient population with prolonged length of stay, putting them at particularly high risk of developing PICS. Second, ECMO is associated with direct neurologic injury, including both macrohemorrhages and microhemorrhages, infarcts, and diffuse hypoxic-ischemic brain injury that likely contribute to long-term outcomes.4 Finally, ECMO is very expensive. A recent study determined that the average cost per admission for patients with COVID-19 placed on ECMO was nearly $850,000 more than those who received only mechanical ventilation.5 Understanding patient-centered outcomes will be an integral part of future cost-effectiveness analyses.

Neuromonitoring of Pediatric and Adult Extracorporeal Membrane Oxygenation Patients: The Importance of Continuous Bedside Tools in Driving Neuroprotective Clinical Care.

Extracorporeal membrane oxygenation (ECMO) is a form of temporary cardiopulmonary bypass for patients with acute respiratory or cardiac failure refractory to conventional therapy. Its usage has become increasingly widespread and while reported survival after ECMO has increased in the past 25 years, the incidence of neurological injury has not declined, leading to the pressing question of how to improve time-to-detection and diagnosis of neurological injury. The neurological status of patients on ECMO is clinically difficult to evaluate due to multiple factors including illness, sedation, and pharmacological paralysis. Thus, increasing attention has been focused on developing tools and techniques to measure and monitor the brain of ECMO patients to identify dynamic risk factors and monitor patients' neurophysiological state as a function in time. Such tools may guide neuroprotective interventions and thus prevent or mitigate brain injury. Current means to continuously monitor and prevent neurological injury in ECMO patients are rather limited; most techniques provide indirect or postinsult recognition of irreversible brain injury. This review will explore the indications, advantages, and disadvantages of standard-of-care, emerging, and investigational technologies for neurological monitoring on ECMO, focusing on bedside techniques that provide continuous assessment of neurological health.

Correlations Between Quantitative EEG Parameters and Cortical Blood Flow in Patients Undergoing Extracorporeal Membrane Oxygenation With and Without Encephalopathy.

PURPOSE: The neurologic examination of patients undergoing extracorporeal membrane oxygenation (ECMO) is crucial for evaluating irreversible encephalopathy but is often obscured by sedation or neuromuscular blockade. Noninvasive neuromonitoring modalities including diffuse correlation spectroscopy and EEG measure cerebral perfusion and neuronal function, respectively. We hypothesized that encephalopathic ECMO patients with greater degree of irreversible cerebral injury demonstrate less correlation between electrographic activity and cerebral perfusion than those whose encephalopathy is attributable to medications. METHODS: We performed a prospective observational study of adults undergoing ECMO who underwent simultaneous continuous EEG and diffuse correlation spectroscopy monitoring. (Alpha + beta)/delta ratio and alpha/delta Rartio derived from quantitative EEG analysis were correlated with frontal cortical blood flow index. Patients who awakened and followed commands during sedation pauses were included in group 1, whereas patients who could not follow commands for most neuromonitoring were placed in group 2. (Alpha + beta)/delta ratio-blood flow index and ADR-BFI correlations were compared between the groups. RESULTS: Ten patients (five in each group) underwent 39 concomitant continuous EEG and diffuse correlation spectroscopy monitoring sessions. Four patients (80%) in each group received some form of analgosedation during neuromonitoring. (Alpha + beta)/delta ratio-blood flow index correlation was significantly lower in group 2 than group 1 (left: 0.05 vs. 0.52, P = 0.03; right: -0.12 vs. 0.39, P = 0.04). Group 2 ADR-BFI correlation was lower only over the right hemisphere (-0.06 vs. 0.47, P = 0.04). CONCLUSIONS: Correlation between (alpha + beta)/delta ratio and blood flow index were decreased in encephalopathic ECMO patients compared with awake ones, regardless of the analgosedation use. The combined use of EEG and diffuse correlation spectroscopy may have utility in monitoring cerebral function in ECMO patients.

Cerebral Blood Flow Hemispheric Asymmetry in Comatose Adults Receiving Extracorporeal Membrane Oxygenation.

Peripheral veno-arterial extracorporeal membrane oxygenation (ECMO) artificially oxygenates and circulates blood retrograde from the femoral artery, potentially exposing the brain to asymmetric perfusion. Though ECMO patients frequently experience brain injury, neurologic exams and imaging are difficult to obtain. Diffuse correlation spectroscopy (DCS) non-invasively measures relative cerebral blood flow (rBF) at the bedside using an optical probe on each side of the forehead. In this study we observed interhemispheric rBF differences in response to mean arterial pressure (MAP) changes in adult ECMO recipients. We recruited 13 subjects aged 21-78 years (7 with cardiac arrest, 4 with acute heart failure, and 2 with acute respiratory distress syndrome). They were dichotomized via Glasgow Coma Scale Motor score (GCS-M) into comatose (GCS-M ≤ 4; n = 4) and non-comatose (GCS-M > 4; n = 9) groups. Comatose patients had greater interhemispheric rBF asymmetry (ASYMrBF) vs. non-comatose patients over a range of MAP values (29 vs. 11%, p = 0.009). ASYMrBF in comatose patients resolved near a MAP range of 70-80 mmHg, while rBF remained symmetric through a wider MAP range in non-comatose patients. Correlations between post-oxygenator pCO2 or pH vs. ASYMrBF were significantly different between comatose and non-comatose groups. Our findings indicate that comatose patients are more likely to have asymmetric cerebral perfusion.

Brain Histopathology of Adult Decedents After Extracorporeal Membrane Oxygenation.

OBJECTIVE: To test the hypothesis that brain injury is more common and varied in patients receiving extracorporeal membrane oxygenation (ECMO) than radiographically observed, we described neuropathology findings of ECMO decedents and associated clinical factors from 3 institutions. METHODS: We conducted a retrospective multicenter observational study of brain autopsies from adult ECMO recipients. Pathology findings were examined for correlation with demographics, clinical data, ECMO characteristics, and outcomes. RESULTS: Forty-three decedents (n = 13 female, median age 47 years) received autopsies after undergoing ECMO for acute respiratory distress syndrome (n = 14), cardiogenic shock (n = 14), and cardiac arrest (n = 15). Median duration of ECMO was 140 hours, most decedents (n = 40) received anticoagulants; 60% (n = 26) underwent venoarterial ECMO, and 40% (n = 17) underwent venovenous ECMO. Neuropathology was found in 35 decedents (81%), including microhemorrhages (37%), macrohemorrhages (35%), infarctions (47%), and hypoxic-ischemic brain injury (n = 17, 40%). Most pathology occurred in frontal neocortices (n = 43 occurrences), basal ganglia (n = 33), and cerebellum (n = 26). Decedents with hemorrhage were older (median age 57 vs 38 years, p = 0.01); those with hypoxic brain injury had higher Sequential Organ Failure Assessment scores (8.0 vs 2.0, p = 0.04); and those with infarction had lower peak Paco2 (53 vs 61 mm Hg, p = 0.04). Six of 9 patients with normal neuroimaging results were found to have pathology on autopsy. The majority underwent withdrawal of life-sustaining therapy (n = 32, 74%), and 2 of 8 patients with normal brain autopsy underwent withdrawal of life-sustaining therapy for suspected neurologic injury. CONCLUSION: Neuropathological findings after ECMO are common, varied, and associated with various clinical factors. Further study on underlying mechanisms is warranted and may guide ECMO management.

Towards detection of brain injury using multimodal non-invasive neuromonitoring in adults undergoing extracorporeal membrane oxygenation.

Extracorporeal membrane oxygenation (ECMO) is a form of cardiopulmonary bypass that provides life-saving support to critically ill patients whose illness is progressing despite maximal conventional support. Use in adults is expanding, however neurological injuries are common. Currently, the existing brain imaging tools are a snapshot in time and require high-risk patient transport. Here we assess the feasibility of measuring diffuse correlation spectroscopy, transcranial Doppler ultrasound, electroencephalography, and auditory brainstem responses at the bedside, and developing a cerebral autoregulation metric. We report preliminary results from two patients, demonstrating feasibility and laying the foundation for future studies monitoring neurological health during ECMO.

Proceedings from the Neurotherapeutics Symposium on Neurological Emergencies: Shaping the Future of Neurocritical Care.

Effective treatment options for patients with life-threatening neurological disorders are limited. To address this unmet need, high-impact translational research is essential for the advancement and development of novel therapeutic approaches in neurocritical care. "The Neurotherapeutics Symposium 2019-Neurological Emergencies" conference, held in Rochester, New York, in June 2019, was designed to accelerate translation of neurocritical care research via transdisciplinary team science and diversity enhancement. Diversity excellence in the neuroscience workforce brings innovative and creative perspectives, and team science broadens the scientific approach by incorporating views from multiple stakeholders. Both are essential components needed to address complex scientific questions. Under represented minorities and women were involved in the organization of the conference and accounted for 30-40% of speakers, moderators, and attendees. Participants represented a diverse group of stakeholders committed to translational research. Topics discussed at the conference included acute ischemic and hemorrhagic strokes, neurogenic respiratory dysregulation, seizures and status epilepticus, brain telemetry, neuroprognostication, disorders of consciousness, and multimodal monitoring. In these proceedings, we summarize the topics covered at the conference and suggest the groundwork for future high-yield research in neurologic emergencies.

Mechanical ventilation in aneurysmal subarachnoid hemorrhage: systematic review and recommendations.

OBJECTIVE: Mechanical ventilation (MV) has a complex interplay with the pathophysiology of aneurysmal subarachnoid hemorrhage (aSAH). We aim to provide a review of the physiology of MV in patients with aSAH, give recommendations based on a systematic review of the literature, and highlight areas that still need investigation. DATA SOURCES: PubMed was queried for publications with the Medical Subject Headings (MeSH) terms "mechanical ventilation" and "aneurysmal subarachnoid hemorrhage" published between January 1, 1990, and March 1, 2020. Bibliographies of returned articles were reviewed for additional publications of interest. STUDY SELECTION: Study inclusion criteria included English language manuscripts with the study population being aSAH patients and the exposure being MV. Eligible studies included randomized controlled trials, observational trials, retrospective trials, case-control studies, case reports, or physiologic studies. Topics and articles excluded included review articles, pediatric populations, non-aneurysmal etiologies of subarachnoid hemorrhage, mycotic and traumatic subarachnoid hemorrhage, and articles regarding tracheostomies. DATA EXTRACTION: Articles were reviewed by one team member, and interpretation was verified by a second team member. DATA SYNTHESIS: Thirty-one articles met the inclusion criteria for this review. CONCLUSIONS: We make recommendations on oxygenation, hypercapnia, PEEP, APRV, ARDS, and intracranial pressure monitoring.

Cognitive, Psychiatric, and Quality of Life Outcomes in Adult Survivors of Extracorporeal Membrane Oxygenation Therapy: A Scoping Review of the Literature.

OBJECTIVES: To perform a scoping literature review of cognitive, psychiatric, and quality of life outcomes in adults undergoing extracorporeal membrane oxygenation for any indication. DATA SOURCES: We searched PubMed, EMBASE, Cochrane Library, Web of Science, CINAHL, and PsycINFO from inception to June 2019. STUDY SELECTION: Observational studies, clinical trials, qualitative studies, and case series with at least 10 adult subjects were included for analysis. Outcomes of interest consisted of general or domain-specific cognition, psychiatric illness, and quality of life measures that included both mental and physical health. DATA EXTRACTION: Study selection, data quality assessment, and interpretation of results were performed by two independent investigators in accordance with the PRISMA statement. DATA SYNTHESIS: Twenty-two articles were included in this review. Six described cognitive outcomes, 12 described psychiatric outcomes of which two were qualitative studies, and 16 described quality of life outcomes. Cognitive impairment was detected in varying degrees in every study that measured it. Three studies examined neuroimaging results and found neurologic injury to be more frequent in venoarterial versus venovenous extracorporeal membrane oxygenation, but described a variable correlation with cognitive impairment. Rates of depression, anxiety, and post-traumatic stress disorder were similar to other critically ill populations and were related to physical disability after extracorporeal membrane oxygenation. Extracorporeal membrane oxygenation survivors' physical quality of life was worse than population norms but tended to improve with time, while mental quality of life did not differ significantly from the general population. Most studies did not include matched controls and instead compared outcomes to previously published values. CONCLUSIONS: Extracorporeal membrane oxygenation survivors experience cognitive impairment, psychiatric morbidity, and worse quality of life compared with the general population and similar to other survivors of critical illness. Physical disability in extracorporeal membrane oxygenation patients plays a significant role in psychiatric morbidity. However, it remains unclear if structural brain injury plays a role in these outcomes and whether extracorporeal membrane oxygenation causes secondary brain injury.