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Application of alpha1-antitrypsin in a rat model of veno-arterial extracorporeal membrane oxygenation.

ABSTRACT: Extracorporeal membrane oxygenation (ECMO) is a life-saving intervention for patients suffering from respiratory or cardiac failure. The ECMO-associated morbidity and mortality depends to a large extent on the underlying disease and is often related to systemic inflammation, consecutive immune paralysis and sepsis. Here we tested the hypothesis that human α1-antitrypsin (SERPINA1) due to its anti-protease and anti-inflammatory functions may attenuate ECMO-induced inflammation. We specifically aimed to test whether intravenous treatment with α1-antitrypsin reduces the release of cytokines in response to 2 h of experimental ECMO. Adult rats were intravenously infused with α1-antitrypsin immediately before starting veno-arterial ECMO. We measured selected pro- and anti-inflammatory cytokines and found, that systemic levels of tumor necrosis factor-α, interleukin-6 and interleukin-10 increase during experimental ECMO. As tachycardia and hypertension developed in response to α1-antitrypsin, a single additional bolus of fentanyl and midazolam was given. Treatment with α1-antitrypsin and higher sedative doses reduced all cytokine levels investigated. We suggest that α1-antitrypsin might have the potential to protect against both ECMO-induced systemic inflammation and immune paralysis. More studies are needed to corroborate our findings, to clarify the mechanisms by which α1-antitrypsin inhibits cytokine release in vivo and to explore the potential application of α1-antitrypsin in clinical ECMO.

SUBMITTER: Edinger F

PROVIDER: S-EPMC8339069 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundEEG-based prognostication studies in intensive care units often rely on a standard 21-electrode montage (stdEEG) requiring substantial human, technical, and financial resources. We here evaluate whether a simplified 4-frontal electrode montage (4-frontEEG) can detect EEG patterns associated with poor outcomes in adult patients under veno-arterial extracorporeal membrane oxygenation (VA-ECMO).MethodsWe conducted a reanalysis of EEG data from a prospective cohort on 118 adult patients under VA-ECMO, in whom EEG was performed on admission to intensive care. EEG patterns of interest included background rhythm, discontinuity, reactivity, and the Synek's score. They were all reassessed by an intensivist on a 4-frontEEG montage, whose analysis was then compared to an expert's interpretation made on stdEEG recordings. The main outcome measure was the degree of correlation between 4-frontEEG and stdEEG montages to identify EEG patterns of interest. The performance of the Synek scores calculated on 4-frontEEG and stdEEG montage to predict outcomes (i.e., 28-day mortality and 90-day Rankin score [Formula: see text]) was investigated in a secondary exploratory analysis.ResultsThe detection of EEG patterns using 4-frontEEG was statistically similar to that of stdEEG for background rhythm (Spearman rank test, ρ = 0.66, p < 0.001), discontinuity (Cohen's kappa, [Formula: see text] = 0.955), reactivity ([Formula: see text] = 0.739) and the Synek's score (ρ = 0.794, p < 0.001). Using the Synek classification, we found similar performances between 4-frontEEG and stdEEG montages in predicting 28-day mortality (AUC 4-frontEEG 0.71, AUC stdEEG 0.68) and for 90-day poor neurologic outcome (AUC 4-frontEEG 0.71, AUC stdEEG 0.66). An exploratory analysis confirmed that the Synek scores determined by 4 or 21 electrodes were independently associated with 28-day mortality and poor 90-day functional outcome.ConclusionIn adult patients under VA-ECMO, a simplified 4-frontal electrode EEG montage interpreted by an intensivist, detected common EEG patterns associated with poor outcomes, with a performance similar to that of a standard EEG montage interpreted by expert neurophysiologists. This simplified montage could be implemented as part of a multimodal evaluation for bedside prognostication.

Project description:Background: To explore the epidemiology, clinical features, risk indicators, and long-term outcomes of neurological complications caused by veno-arterial extracorporeal membrane oxygenation (V-A ECMO). Methods: We retrospectively analyzed 60 adult patients who underwent V-A ECMO support in our unit from February 2012 to August 2020. These patients were separated into the neurological complications group (NC group) and the non-neurological complications group (nNC group). The differences in basic data and ECMO data between the two groups were compared. The data of long-term neurological prognosis were collected by telephone follow-up. Results: Thirty-nine patients (65.0%) had neurological complications. There were significant differences between the two groups in terms of median age, hypertension, median blood urea nitrogen, median troponin I (TNI), median lactic acid, pre-ECMO percutaneous coronary intervention, continuous renal replacement therapy (CRRT), median Sequential Organ Failure Assessment score, median Acute Physiology and Chronic Health Evaluation II score, median peak inspiratory pressure, median positive end expiratory pressure, and median fresh frozen plasma (P < 0.05). The median Intensive Care Unit length of stay (ICU LOS), 28-day mortality, median post-ECMO vasoactive inotropic score, non-pulsate perfusion (NP), and median ECMO duration of the NC group were significantly higher than those of the nNC group (P < 0.05). Furthermore, multiple logistic regression analysis revealed that TNI (P = 0.043), CRRT (P = 0.047), and continuous NP > 12 h (P = 0.043) were independent risk indicators for neurological complications in patients undergoing ECMO. Forty-four patients (73.3%) survived after discharge, and 38 patients (63.3%) had Cerebral Performance Category score of 1-2. And there were significant differences between the two groups in long-term neurological outcomes after discharge for 6 months (P < 0.05). Conclusion: The incidence of neurological complications was higher in patients undergoing V-A ECMO and was closely related to adverse outcomes (including ICU LOS and 28-day mortality). TNI, CRRT, and continuous NP > 12 h were independent risk indicators for predicting neurological complications in ECMO supporting patients. And the neurological complications of patients during ECMO support had significant adverse effect on long-term surviving and neurological outcomes of patients after discharge for 6 months.

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Application of alpha1-antitrypsin in a rat model of veno-arterial extracorporeal membrane oxygenation.

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