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      Brain Histopathology of Adult Decedents After Extracorporeal Membrane Oxygenation

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          Abstract

          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 Pa co 2 (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.

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          Most cited references41

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          The inflammatory response to extracorporeal membrane oxygenation (ECMO): a review of the pathophysiology

          Extracorporeal membrane oxygenation (ECMO) is a technology capable of providing short-term mechanical support to the heart, lungs or both. Over the last decade, the number of centres offering ECMO has grown rapidly. At the same time, the indications for its use have also been broadened. In part, this trend has been supported by advances in circuit design and in cannulation techniques. Despite the widespread adoption of extracorporeal life support techniques, the use of ECMO remains associated with significant morbidity and mortality. A complication witnessed during ECMO is the inflammatory response to extracorporeal circulation. This reaction shares similarities with the systemic inflammatory response syndrome (SIRS) and has been well-documented in relation to cardiopulmonary bypass. The exposure of a patient’s blood to the non-endothelialised surface of the ECMO circuit results in the widespread activation of the innate immune system; if unchecked this may result in inflammation and organ injury. Here, we review the pathophysiology of the inflammatory response to ECMO, highlighting the complex interactions between arms of the innate immune response, the endothelium and coagulation. An understanding of the processes involved may guide the design of therapies and strategies aimed at ameliorating inflammation during ECMO. Likewise, an appreciation of the potentially deleterious inflammatory effects of ECMO may assist those weighing the risks and benefits of therapy.
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            Changes in rates of autopsy-detected diagnostic errors over time: a systematic review.

            Substantial discrepanies exist between clinical diagnoses and findings at autopsy. Autopsy may be used as a tool for quality management to analyze diagnostic discrepanies. To determine the rate at which autopsies detect important, clinically missed diagnoses, and the extent to which this rate has changed over time. A systematic literature search for English-language articles available on MEDLINE from 1966 to April 2002, using the search terms autopsy, postmortem changes, post-mortem, postmortem, necropsy, and posthumous, identified 45 studies reporting 53 distinct autopsy series meeting prospectively defined criteria. Reference lists were reviewed to identify additional studies, and the final bibliography was distributed to experts in the field to identify missing or unpublished studies. Included studies reported clinically missed diagnoses involving a primary cause of death (major errors), with the most serious being those likely to have affected patient outcome (class I errors). Logistic regression was performed using data from 53 distinct autopsy series over a 40-year period and adjusting for the effects of changes in autopsy rates, country, case mix (general autopsies; adult medical; adult intensive care; adult or pediatric surgery; general pediatrics or pediatric inpatients; neonatal or pediatric intensive care; and other autopsy), and important methodological features of the primary studies. Of 53 autopsy series identified, 42 reported major errors and 37 reported class I errors. Twenty-six autopsy series reported both major and class I error rates. The median error rate was 23.5% (range, 4.1%-49.8%) for major errors and 9.0% (range, 0%-20.7%) for class I errors. Analyses of diagnostic error rates adjusting for the effects of case mix, country, and autopsy rate yielded relative decreases per decade of 19.4% (95% confidence interval [CI], 1.8%-33.8%) for major errors and 33.4% (95% [CI], 8.4%-51.6%) for class I errors. Despite these decreases, we estimated that a contemporary US institution (based on autopsy rates ranging from 100% [the extrapolated extreme at which clinical selection is eliminated] to 5% [roughly the national average]), could observe a major error rate from 8.4% to 24.4% and a class I error rate from 4.1% to 6.7%. The possibility that a given autopsy will reveal important unsuspected diagnoses has decreased over time, but remains sufficiently high that encouraging ongoing use of the autopsy appears warranted.
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              Hypoxic-ischemic brain injury: pathophysiology, neuropathology and mechanisms.

              Hypoxic-ischemic brain injury is a well known consequence of cardiac arrest. Variable injuries can occur with purely hypoxic or histotoxic insults such as asphyxiation and carbon monoxide poisoning. The injury may happen at the time of the insult, but there may also be continued damage after circulation and oxygenation are reestablished. The nature and extent of the damage appears to depend on the severity, time course and duration of the oxygen deprivation and lack of blood supply, as well as on the underlying mechanism. This review describes the pathophysiological and molecular basis of hypoxic ischemic brain injury, and differentiates between the mechanisms of injury by cardiac arrest, pure respiratory arrest, and arrest secondary to cytotoxicity (e.g. carbon monoxide poisoning).
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                Author and article information

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                Journal
                Neurology
                Neurology
                Ovid Technologies (Wolters Kluwer Health)
                0028-3878
                1526-632X
                March 01 2021
                March 02 2021
                March 02 2021
                January 20 2021
                : 96
                : 9
                : e1278-e1289
                Article
                10.1212/WNL.0000000000011525
                33472914
                5b9fddb8-9ed9-4d29-85f3-2669f4c4ed74
                © 2021
                History

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