1
|
Lin Z, Liao Y, Tian D, Liao J, Chen Q, Yin J. Small-Molecule Fluorescent Probes for Butyrylcholinesterase. ChemMedChem 2025; 20:e202400875. [PMID: 39714828 DOI: 10.1002/cmdc.202400875] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/01/2024] [Revised: 12/16/2024] [Accepted: 12/19/2024] [Indexed: 12/24/2024]
Abstract
Butyrylcholinesterase plays an indispensable role in organisms, and its abnormal expression poses a significant threat to human health and safety, covering various aspects including liver-related diseases, diabetes, obesity, cardiovascular and cerebrovascular diseases, and neurodegenerative diseases. In addition, toxic substances such as organophosphorus and carbamate pesticides markedly inhibit BChE activity. BChE activity serves as a critical parameter for the clinical diagnosis of acute organophosphorus pesticide poisoning and the evaluation of organophosphorus and carbamate pesticide residues. Therefore, the accurate and reliable detection of butyrylcholinesterase activity is particularly urgent and important for in-depth analysis of its biological function, diagnosis and therapy of related diseases, drug screening and sensitive detection of pesticide residues. Fluorescent probes have become a promising tool for sensing and imaging of butyrylcholinesterase, due to its advantages of high spatio-temporal resolution, high selectivity, non-invasive, high sensitivity, and tailored molecule structures. Here, this paper provides a comprehensive overview of the research progress in the sensing, imaging and therapy of butyrylcholinesterase utilizing fluorescent probes. This paper might be a useful guideline for researchers to design new high-performance fluorescence probes for BChE, and making further contributions to this intriguing field.
Collapse
Affiliation(s)
- Zibo Lin
- State Key Laboratory of Green Pesticide, International Joint Research Center for Intelligent Biosensor Technology and Health, College of chemistry, Central China Normal University, Wuhan, 430079, P.R. China
| | - Yuanyuan Liao
- State Key Laboratory of Green Pesticide, International Joint Research Center for Intelligent Biosensor Technology and Health, College of chemistry, Central China Normal University, Wuhan, 430079, P.R. China
| | - Donglei Tian
- State Key Laboratory of Green Pesticide, International Joint Research Center for Intelligent Biosensor Technology and Health, College of chemistry, Central China Normal University, Wuhan, 430079, P.R. China
| | - Junyu Liao
- State Key Laboratory of Green Pesticide, International Joint Research Center for Intelligent Biosensor Technology and Health, College of chemistry, Central China Normal University, Wuhan, 430079, P.R. China
| | - Qiong Chen
- State Key Laboratory of Green Pesticide, International Joint Research Center for Intelligent Biosensor Technology and Health, College of chemistry, Central China Normal University, Wuhan, 430079, P.R. China
| | - Jun Yin
- State Key Laboratory of Green Pesticide, International Joint Research Center for Intelligent Biosensor Technology and Health, College of chemistry, Central China Normal University, Wuhan, 430079, P.R. China
| |
Collapse
|
2
|
Liao Z, Luo D, Tang X, Huang F, Zhang X. MRI-based radiomics for predicting pathological complete response after neoadjuvant chemoradiotherapy in locally advanced rectal cancer: a systematic review and meta-analysis. Front Oncol 2025; 15:1550838. [PMID: 40129922 PMCID: PMC11930822 DOI: 10.3389/fonc.2025.1550838] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/24/2024] [Accepted: 02/20/2025] [Indexed: 03/26/2025] Open
Abstract
Purpose To evaluate the value of MRI-based radiomics for predicting pathological complete response (pCR) after neoadjuvant chemoradiotherapy (NCRT) in patients with locally advanced rectal cancer (LARC) through a systematic review and meta-analysis. Methods A systematic literature search was conducted in PubMed, Embase, Proquest, Cochrane Library, and Web of Science databases, covering studies up to July 1st, 2024, on the diagnostic accuracy of MRI radiomics for predicting pCR in LARC patients following NCRT. Two researchers independently evaluated and selected studies using the Quality Assessment of Diagnostic Accuracy Studies 2 (QUADAS-2) tool and the Radiomics Quality Score (RQS) tool. A random-effects model was employed to calculate the pooled sensitivity, specificity, and diagnostic odds ratio (DOR) for MRI radiomics in predicting pCR. Meta-regression and subgroup analyses were performed to explore potential sources of heterogeneity. Statistical analyses were performed using RevMan 5.4, Stata 17.0, and Meta-Disc 1.4. Results A total of 35 studies involving 9,696 LARC patients were included in this meta-analysis. The average RQS score of the included studies was 13.91 (range 9.00-24.00), accounting for 38.64% of the total score. According to QUADAS-2, there were risks of bias in patient selection and flow and timing domain, though the overall quality of the studies was acceptable. MRI-based radiomics showed no significant threshold effect in predicting pCR (Spearman correlation coefficient=0.119, P=0.498) but exhibited high heterogeneity (I2≥50%). The pooled sensitivity, specificity, positive likelihood ratio, negative likelihood ratio and DOR were 0.83, 0.82, 5.1, 0.23 and 27.22 respectively, with an area under the summary receiver operating characteristic (sROC) curve of 0.91. According to joint model analysis, publication year, country, multi-magnetic field strength, multi-MRI sequence, ROI structure, contour consistency, feature extraction software, and feature quantity after feature dimensionality reduction were potential sources of heterogeneity. Deeks' funnel plot suggested no significant publication bias (P=0.69). Conclusions MRI-based radiomics demonstrates high efficacy for predicting pCR in LARC patients following NCRT, holding significant promise for informing clinical decision-making processes and advancing individualized treatment in rectal cancer patients. Systematic review registration https://www.crd.york.ac.uk/prospero/, identifier CRD42024611733.
Collapse
Affiliation(s)
| | | | | | | | - Xuhui Zhang
- Department of Oncology, Sichuan Provincial People’s Hospital, University of Electronic Science and Technology of China, Chengdu, China
| |
Collapse
|
3
|
Sridhar GR, Gumpeny L. Emerging significance of butyrylcholinesterase. World J Exp Med 2024; 14:87202. [PMID: 38590305 PMCID: PMC10999061 DOI: 10.5493/wjem.v14.i1.87202] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/28/2023] [Revised: 10/04/2023] [Accepted: 01/05/2024] [Indexed: 03/19/2024] Open
Abstract
Butyrylcholinesterase (BChE; EC 3.1.1.8), an enzyme structurally related to acetylcholinesterase, is widely distributed in the human body. It plays a role in the detoxification of chemicals such as succinylcholine, a muscle relaxant used in anesthetic practice. BChE is well-known due to variant forms of the enzyme with little or no hydrolytic activity which exist in some endogamous communities and result in prolonged apnea following the administration of succinylcholine. Its other functions include the ability to hydrolyze acetylcholine, the cholinergic neurotransmitter in the brain, when its primary hydrolytic enzyme, acetylcholinesterase, is absent. To assess its potential roles, BChE was studied in relation to insulin resistance, type 2 diabetes mellitus, cognition, hepatic disorders, cardiovascular and cerebrovascular diseases, and inflammatory conditions. Individuals who lack the enzyme activity of BChE are otherwise healthy, until they are given drugs hydrolyzed by this enzyme. Therefore, BChE is a candidate for the study of loss-of-function mutations in humans. Studying individuals with variant forms of BChE can provide insights into whether they are protected against metabolic diseases. The potential utility of the enzyme as a biomarker for Alzheimer's disease and the response to its drug treatment can also be assessed.
Collapse
Affiliation(s)
- Gumpeny R Sridhar
- Department of Endocrinology and Diabetes, Endocrine and Diabetes Centre, Visakhapatnam 530002, Andhra Pradesh, India
| | - Lakshmi Gumpeny
- Department of Internal Medicine, Gayatri Vidya Parishad Institute of Healthcare and Medical Technology, Visakhapatnam 530048, Andhra Pradesh, India
| |
Collapse
|
4
|
Gruendel MS, Brenneisen W, Wollborn J, Haaker G, Meersch M, Gurlit S, Goebel U. Perioperative point-of-care-testing of plasmacholinesterases identifies older patients at risk for postoperative delirium: an observational prospective cohort study. BMC Geriatr 2024; 24:136. [PMID: 38321383 PMCID: PMC10848373 DOI: 10.1186/s12877-023-04627-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/30/2023] [Accepted: 12/20/2023] [Indexed: 02/08/2024] Open
Abstract
BACKGROUND Postoperative delirium (POD) is a severe perioperative complication that may increase mortality and length-of-stay in older patients. Moreover, POD is a major economic burden to any healthcare system. An altered expression of Acetylcholine- and Butyrylcholinesterases (AChE, BuChE) due to an unbalanced neuroinflammatory response to trauma or an operative stimulus has been reported to play an essential role in the development of POD. We investigated if perioperative measurement of cholinesterases (ChEs) can help identifying patients at risk for the occurrence of POD in both, scheduled and emergency surgery patients. METHODS This monocentric prospective observational cohort study was performed in a tertiary hospital (departments of orthopaedic surgery and traumatology). One hundred and fifty-one patients aged above 75 years were enrolled for scheduled (n = 76) or trauma-related surgery (n = 75). Exclusion criteria were diagnosed dementia and anticholinergic medication. Plasma samples taken pre- and postoperatively were analysed regarding AChE and BuChE activity. Furthermore, perioperative assessment using different cognitive tests was performed. The type of anaesthesia (general vs. spinal anaesthesia) was analysed. Primary outcome was the incidence of POD assessed by the approved Confusion Assessment Method (CAM) in combination with the expression of AChE and BuChE. RESULTS Of 151 patients included, 38 (25.2%) suffered from POD; 11 (14%) in scheduled and 27 (36%) in emergency patients. AChE levels showed no difference throughout groups or time course. Trauma patients had lower BuChE levels prior to surgery than scheduled patients (p < 0.001). Decline in BuChE levels correlated positively with the incidence of POD (1669 vs. 1175 U/l; p < 0.001). Emergency patients with BuChE levels below 1556 U/L were at highest risk for POD. There were no differences regarding length of stay between groups or incidence of POD. The type of anaesthesia had no influence regarding the incidence of POD. Only Charlson Comorbidity Index and Mini Nutrition Assessment demonstrated reliable strength in respect of POD. CONCLUSIONS Perioperative measurement of BuChE activity can be used as a tool to identify patients at risk of POD. As a point-of-care test, quick results may alter the patients' course prior to the development of POD. TRIAL REGISTRATION https://drks.de/search/de/trial/DRKS00017178 .
Collapse
Affiliation(s)
- Matthias S Gruendel
- Department of Anaesthesiology and Critical Care, St. Franziskus-Hospital GmbH, Hohenzollernring 70, Muenster, 48145, Germany
| | - Wibke Brenneisen
- Department of Anaesthesiology and Critical Care, St. Franziskus-Hospital GmbH, Hohenzollernring 70, Muenster, 48145, Germany
| | - Jakob Wollborn
- Department of Anaesthesiology, Perioperative and Pain Medicine, Harvard Medical School, Brigham and Women's Hospital, Boston, USA
| | - Gerrit Haaker
- Department of Anaesthesiology and Critical Care, St. Franziskus-Hospital GmbH, Hohenzollernring 70, Muenster, 48145, Germany
| | - Melanie Meersch
- Department of Anaesthesiology, Intensive Care and Pain Medicine, University Hospital Muenster, Muenster, Germany
| | - Simone Gurlit
- Department of Anaesthesiology and Critical Care, St. Franziskus-Hospital GmbH, Hohenzollernring 70, Muenster, 48145, Germany
- Department of Public Health, District Council, Muenster, Germany
| | - Ulrich Goebel
- Department of Anaesthesiology and Critical Care, St. Franziskus-Hospital GmbH, Hohenzollernring 70, Muenster, 48145, Germany.
| |
Collapse
|
5
|
Piggott KD, Norlin C, Laviolette C, Turner J, Lewis L, Soliman A, Hebert D, Pettitt T. Nucleated red blood cells as a biomarker for mortality in infants and neonates requiring veno-arterial extracorporeal membrane oxygenation for cardiac disease. Perfusion 2023; 38:299-304. [PMID: 34636269 DOI: 10.1177/02676591211050607] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022]
Abstract
INTRODUCTION Nucleated red blood cells (NRBC) are rare in the peripheral circulation of healthy individuals and their presence have been associated with mortality in adults and very low birth weight newborns, however, its value as a biomarker for mortality in infants requiring veno-arterial (VA) extracorporeal membrane oxygenation (ECMO) has yet to be studied. We sought to determine if NRBC can serve as a biomarker for ECMO mortality and inpatient mortality in infants requiring V-A ECMO. METHODS A single-center retrospective chart review analyzing infants <1 year of age requiring VA ECMO due to myocardial dysfunction or post-cardiotomy between January 1, 2011 to June 30, 2020. RESULTS One hundred two patients required VA ECMO. Sixty-five patients required ECMO post-cardiotomy, 19 for perioperative deterioration, and 18 for myocardial dysfunction. Fifty-one patients (50%) died (21 died on ECMO, 30 died post-ECMO decannulation). Multivariable analysis found Age <60 days (OR 13.0, 95% CI 1.9-89.6, p = 0.009), NRBC increase by >50% post-ECMO decannulation (OR 17.1, 95% CI 3.1-95.1, p = 0.001), Single Ventricle (OR 9.0, 95% CI 1.7-47.7, p = 0.01), and lactate at ECMO decannulation (OR 3.0, 95% CI 1.3-7.1, p = 0.011) to be independently associated with inpatient mortality. ROC curves evaluating NRBC pre-ECMO decannulation as a biomarker for mortality on ECMO (AUC 0.80, 95% CI 0.68-0.92, p ⩽ 0.001) and post-ECMO decannulation (AUC 0.75, 95% CI 0.65-0.84, p ⩽ 0.001) show NRBC to be an accurate biomarker for mortality. CONCLUSIONS Greater than 50% increase in NRBC post-ECMO decannulation is associated with inpatient mortality. NRBC value pre-ECMO decannulation may be a useful biomarker for mortality while on ECMO and post-decannulation.
Collapse
Affiliation(s)
- Kurt D Piggott
- Division of Pediatric Cardiac Intensive Care, Louisiana State University Health Sciences, New Orleans, LA, USA
| | - Casey Norlin
- Lousiana State University Health Sciences, New Orleans, LA, USA
| | - Cynthia Laviolette
- Division of Pediatric Cardiac Intensive Care, Louisiana State University Health Sciences, New Orleans, LA, USA
| | - Jason Turner
- Division of Pediatric Cardiac Intensive Care, Louisiana State University Health Sciences, New Orleans, LA, USA
| | - LaTasha Lewis
- Division of Pediatric Cardiac Intensive Care, Louisiana State University Health Sciences, New Orleans, LA, USA
| | - Amira Soliman
- Division of Pediatric Cardiac Intensive Care, Louisiana State University Health Sciences, New Orleans, LA, USA
| | - David Hebert
- Lousiana State University Health Sciences, New Orleans, LA, USA
| | - Tim Pettitt
- Lousiana State University Health Sciences, New Orleans, LA, USA
| |
Collapse
|
6
|
Espeter F, Künne D, Garczarek L, Kuhlmann H, Skarabis A, Zivkovic AR, Brenner T, Schmidt K. Critically Ill COVID-19 Patients Show Reduced Point of Care-Measured Butyrylcholinesterase Activity—A Prospective, Monocentric Observational Study. Diagnostics (Basel) 2022; 12:diagnostics12092150. [PMID: 36140551 PMCID: PMC9498245 DOI: 10.3390/diagnostics12092150] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/02/2022] [Revised: 08/29/2022] [Accepted: 09/02/2022] [Indexed: 01/08/2023] Open
Abstract
A biomarker for risk stratification and disease severity assessment in SARS-CoV-2 infections has not yet been established. Point of care testing (POCT) of butyrylcholinesterase (BChE) enables early detection of systemic inflammatory responses and correlates with disease severity in sepsis and burns. In acute care or resource-limited settings, POCT facilitates rapid clinical decision making, a particularly beneficial aspect in the management of pandemic situations. In this prospective observational study, POCT-measured BChE activity was assessed in 52 critically ill COVID-19 patients within 24 h of ICU admission and on the third and seventh day after ICU admission. Forty (77%) of these patients required venovenous extracorporeal membrane oxygenation (vvECMO). In critically ill COVID-19 patients, BChE activity is significantly decreased compared with healthy subjects, but also compared with other inflammatory conditions such as sepsis, burns, or trauma. POCT BChE activity reflects the severity of organ dysfunction and allows prediction of 28-day mortality in critically ill COVID-19 patients. Implementing early POCT BChE measurement could facilitate risk stratification and support admission and transfer decisions in resource-limited settings.
Collapse
Affiliation(s)
- Florian Espeter
- Department of Anesthesiology and Intensive Care Medicine, University Hospital Essen, University Duisburg-Essen, 45147 Essen, Germany
- Correspondence: ; Tel.: +49-201-723-84485
| | - David Künne
- Department of Anesthesiology and Intensive Care Medicine, University Hospital Essen, University Duisburg-Essen, 45147 Essen, Germany
| | - Lena Garczarek
- Department of Anesthesiology and Intensive Care Medicine, University Hospital Essen, University Duisburg-Essen, 45147 Essen, Germany
| | - Henning Kuhlmann
- Department of Anesthesiology and Intensive Care Medicine, University Hospital Essen, University Duisburg-Essen, 45147 Essen, Germany
| | - Annabell Skarabis
- Department of Anesthesiology and Intensive Care Medicine, University Hospital Essen, University Duisburg-Essen, 45147 Essen, Germany
| | | | - Thorsten Brenner
- Department of Anesthesiology and Intensive Care Medicine, University Hospital Essen, University Duisburg-Essen, 45147 Essen, Germany
| | - Karsten Schmidt
- Department of Anesthesiology and Intensive Care Medicine, University Hospital Essen, University Duisburg-Essen, 45147 Essen, Germany
| |
Collapse
|
7
|
Schick B, Barth E, Mayer B, Weber CL, Hagemeyer T, Schönfeldt C. Prospective, observational, single-centre cohort study with an independent control group matched for age and sex aimed at investigating the significance of cholinergic activity in patients with schizophrenia: study protocol of the CLASH-study. BMJ Open 2021; 11:e050501. [PMID: 34930729 PMCID: PMC8689167 DOI: 10.1136/bmjopen-2021-050501] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/24/2022] Open
Abstract
INTRODUCTION Alterations in the cholinergic metabolism may cause various clinical symptoms of schizophrenia. In addition to the 'monoamine hypothesis,' neuroinflammation is also discussed as a cause of schizophrenia. To date, there has been no evidence of alterations in the central cholinergic transmitter balance in patients with schizophrenia under clinical conditions. By contrast, studies in critically ill patients have established the measurement of acetylcholinesterase activity as a suitable surrogate parameter of central cholinergic transmitter balance/possible pathophysiological changes. Butyrylcholinesterase activity has been established as a parameter indicating possible (neuro)inflammatory processes. Both parameters can now be measured using a point-of-care approach. Therefore, the primary objective of this study is to investigate whether acetylcholinesterase and butyrylcholinesterase activity differs in patients with various forms of schizophrenia. Secondary objectives address the possible association between acetylcholinesterase and butyrylcholinesterase activity and (1) schizophrenic symptoms using the Positive and Negative Syndrome Scale, (2) the quantity of antipsychotics taken and (3) the duration of illness. METHODS AND ANALYSIS The study is designed as a prospective, observational cohort study with one independent control group. It is being carried out at the Department of Psychiatry and Psychotherapy III, Ulm University Hospital, Germany. Patient enrolment started in October 2020, and the anticipated end of the study is in January 2022. The enrolment period was set from October 2020 to December 2021 (extension required due to SARS-CoV-2 pandemic). The sample size is calculated at 50 patients in each group. Esterase activity is measured on hospital admission (acute symptomatology) and after referral to a postacute ward over a period of three consecutive days. The matched control group will be created after reaching 50 patients with schizophrenia. This will be followed by a comprehensive statistical analysis of the data set. ETHICS AND DISSEMINATION The study was registered prospectively in the German Clinical Trials Register (DRKS-ID: DRKS00023143,URL: https://www.drks.de/drks_web/navigate.do?navigationId=trial.HTML&TRIAL_ID=DRKS00023143) after approval by the ethics committee of the University of Ulm, Germany Trial Code No. 280/20. TRIAL REGISTRATION NUMBER DRKS00023143; Pre-results.
Collapse
Affiliation(s)
- Benedikt Schick
- Department of Anaesthesiology, University Hospital Ulm, Ulm, Germany
| | - Eberhard Barth
- Department of Anaesthesiology, University Hospital Ulm, Ulm, Germany
| | - Benjamin Mayer
- Institute of Epidemiology and Medical Biometry, University of Ulm, Ulm, Germany
| | - Claire-Louise Weber
- Department of Psychiatry and Psychotherapy III, University Hospital Ulm, Ulm, Germany
| | - Theresa Hagemeyer
- Department of Psychiatry and Psychotherapy III, University Hospital Ulm, Ulm, Germany
| | - Carlos Schönfeldt
- Department of Psychiatry and Psychotherapy III, University Hospital Ulm, Ulm, Germany
| |
Collapse
|
8
|
Michels B, Holzamer A, Graf BM, Bredthauer A, Petermichl W, Müller A, Zausig YA, Bitzinger DI. Butyrylcholinesterase as a perioperative complication marker in patients after transcatheter aortic valve implantation: a prospective observational study. BMJ Open 2021; 11:e042857. [PMID: 34230011 PMCID: PMC8261881 DOI: 10.1136/bmjopen-2020-042857] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/09/2023] Open
Abstract
OBJECTIVES Transcatheter aortic valve implantation (TAVI) is performed in elderly patients with severe aortic valve stenosis and increased operative risks. We tested the hypothesis that acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) have a predictive value for prevalent complications after TAVI and could serve as indicators of systemic inflammation in the early postoperative period. DESIGN Prospective observational study. SETTING This study is a secondary analysis of multicentre CESARO- study. PARTICIPANTS 48 patients with TAVI were included and 43 obtained the complete assessment. PRIMARY AND SECONDARY OUTCOME MEASURES Patients' clinical parameters, demographic data, peripheral AChE and BChE activities and routine blood markers were assessed throughout the perioperative period using bedside point-of-care measurements for AChE and BChE. Postoperative complication screening was conducted up to the third postoperative day and included infections, delirium and heart-rhythm disturbances. After assessment, the patients were divided into complication and noncomplication group. RESULTS Of 43 patients, 24 developed postsurgical complications (55.8%). Preoperative assessment showed no significant differences regarding demographic data and laboratory markers, but preoperative BChE levels were significantly lower in patients who developed postoperative complications (complication group 2589.2±556.4 vs noncomplication group 3295.7±628.0, Cohen's r=0.514, p<0.001). In complication group, we observed an early, sustained reduction in BChE activity from preoperative to postoperative period. In complication group, BChE levels were significantly lower at each time point compared with noncomplication group. AChE activity showed no significant difference between both groups. Complication group also had longer stay in hospital overall. CONCLUSION BChE could be a useful perioperative biomarker to identify patients with a higher risk for postoperative complications after TAVI. By using point-of-care measurements, the levels of BChE are fast available and can lead to an early targeted therapy. Predicting the length of the hospital stay might play an important role in staff and resource management for these patients. TRIAL REGISTRATION NUMBER NCT01964274; Post-results.
Collapse
Affiliation(s)
- Bernhard Michels
- Department of Gastroenterology, University Hospital Regensburg, Regensburg, Germany
| | - Andreas Holzamer
- Department of Cardiothoracic Surgery, University Hospital Regensburg, Regensburg, Germany
| | - Bernhard M Graf
- Department of Anesthesiology, University Hospital Regensburg, Regensburg, Germany
| | - Andre Bredthauer
- Department of Neurology - Center of Vascular Neurology and Intensive Care Medicine, University of Regensburg, Regensburg, Germany
| | - Walter Petermichl
- Department of Anesthesiology, University Hospital Regensburg, Regensburg, Germany
| | - Anika Müller
- Department of Anesthesiology and Intensive Care Medicine, Campus Charité Mitte and Campus Virchow-Klinikum, Charité Universitätsmedizin Berlin, Berlin, Germany
| | - York Alexander Zausig
- Department of Anesthesiology and Intensive Care Medicine, Klinikum Aschaffenburg-Alzenau, Aschaffenburg, Germany
| | - Diane Inge Bitzinger
- Department of Anesthesiology, University Hospital Regensburg, Regensburg, Germany
| |
Collapse
|
9
|
Schrutka L, Rohmann F, Binder C, Haberl T, Dreyfuss B, Heinz G, Lang IM, Felli A, Steinlechner B, Niessner A, Laufer G, Goliasch G, Wiedemann D, Distelmaier K. Discriminatory power of scoring systems for outcome prediction in patients with extracorporeal membrane oxygenation following cardiovascular surgery†. Eur J Cardiothorac Surg 2020; 56:534-540. [PMID: 30789227 DOI: 10.1093/ejcts/ezz040] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/09/2018] [Revised: 01/09/2019] [Accepted: 01/13/2019] [Indexed: 12/30/2022] Open
Abstract
OBJECTIVES Although extracorporeal membrane oxygenation (ECMO) represents a rapidly evolving treatment option in patients with refractory heart or lung failure, survival remains poor and appropriate risk stratification challenging because established risk prediction models have not been validated for this specific population. METHODS This observational single-centre registry included a total of 240 patients treated with venoarterial ECMO therapy following cardiovascular surgery and analysed the discriminatory power of the European System of Cardiac Operative Risk Evaluation (EuroSCORE) additive, the EuroSCORE II, the Sequential Organ Failure Assessment (SOFA) score, the Simplified Acute Physiology Score (SAPS) II, the SAPS III, the Acute Physiology and Chronic Health Evaluation (APACHE) II, the Risk of renal failure, Injury to the kidney, Failure of kidney function, Loss of kidney function and End-stage renal failure (RIFLE) classification, the survival after venoarterial ECMO (SAVE) score, the prEdictioN of Cardiogenic shock OUtcome foR AMI patients salvaGed by VA-ECMO (ENCOURAGE) score and the Society of Thoracic Surgeons (STS) risk model for outcome prediction. RESULTS During a median follow-up time of 37 months (interquartile range 19-67), 65% of the patients died. Only the SAVE score and the SAPS II were significantly associated with the 30-day mortality rate with a hazard ratio (HR) of 1.06 [95% confidence interval (CI) 1.02-1.11; P = 0.002] for the SAVE score and an HR of 1.02 (95% CI 1.01-1.03; P = 0.004) for the SAPS II with a modest discriminatory power displayed by a C-index of 0.61 and 0.57, respectively. Seven out of 10 scoring systems revealed significant association with long-term mortality, with the SAVE score and the SAPS II remaining the strongest predictors of long-term mortality with an HR of 1.06 (95% CI 1.03-1.09; P < 0.001, C-index 0.61) for the SAVE score and an HR of 1.02 (95% CI 1.01-1.03; P < 0.001, C-index 0.58) for the SAPS II. CONCLUSIONS Risk assessment based on established risk models in patients with ECMO remains difficult. Only the SAPS II and the SAVE score were exclusively found to be suitable for short- and long-term outcome prediction in this specific vulnerable patient population.
Collapse
Affiliation(s)
- Lore Schrutka
- Department of Internal Medicine II, Medical University of Vienna, Vienna, Austria
| | - Felix Rohmann
- Department of Internal Medicine II, Medical University of Vienna, Vienna, Austria
| | - Christina Binder
- Department of Internal Medicine II, Medical University of Vienna, Vienna, Austria
| | - Thomas Haberl
- Department of Internal Medicine II, Medical University of Vienna, Vienna, Austria
| | - Ben Dreyfuss
- Department of Cardiothoracic Surgery, Medical University of Vienna, Vienna, Austria
| | - Gottfried Heinz
- Department of Internal Medicine II, Medical University of Vienna, Vienna, Austria
| | - Irene M Lang
- Department of Internal Medicine II, Medical University of Vienna, Vienna, Austria
| | - Alessia Felli
- Department of Cardiothoracic and Vascular Anaesthesia and Intensive Care Medicine, Medical University of Vienna, Vienna, Austria
| | - Barbara Steinlechner
- Department of Cardiothoracic and Vascular Anaesthesia and Intensive Care Medicine, Medical University of Vienna, Vienna, Austria
| | - Alexander Niessner
- Department of Internal Medicine II, Medical University of Vienna, Vienna, Austria
| | - Günther Laufer
- Department of Cardiothoracic Surgery, Medical University of Vienna, Vienna, Austria
| | - Georg Goliasch
- Department of Internal Medicine II, Medical University of Vienna, Vienna, Austria
| | - Dominik Wiedemann
- Department of Cardiothoracic Surgery, Medical University of Vienna, Vienna, Austria
| | - Klaus Distelmaier
- Department of Internal Medicine II, Medical University of Vienna, Vienna, Austria
| |
Collapse
|
10
|
Amin F, Lombardi J, Alhussein M, Posada JD, Suszko A, Koo M, Fan E, Ross H, Rao V, Alba AC, Billia F. Predicting Survival After VA-ECMO for Refractory Cardiogenic Shock: Validating the SAVE Score. CJC Open 2020; 3:71-81. [PMID: 33458635 PMCID: PMC7801193 DOI: 10.1016/j.cjco.2020.09.011] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/21/2020] [Accepted: 09/04/2020] [Indexed: 01/08/2023] Open
Abstract
Background Veno-arterial extracorporeal membrane oxygenation (VA-ECMO) is used increasingly to support patients who are in cardiogenic shock. Due to the risk of complications, prediction models may aid in identifying patients who would benefit most from VA-ECMO. One such model is the Survival After Veno-Arterial Extracorporeal Membrane Oxygenation (SAVE) score. Therefore, we wanted to validate the utility of the SAVE score in a contemporary cohort of adult patients. Methods Retrospective data were extracted from electronic health records of 120 patients with cardiogenic shock supported with VA-ECMO between 2011 and 2018. The SAVE score was calculated for each patient to predict survival to hospital discharge. We assessed the SAVE score calibration by comparing predicted vs observed survival at discharge. We assessed discrimination with the area under the receiver operating curve using logistic regression. Results A total of 45% of patients survived to hospital discharge. Survivors had a significantly higher mean SAVE score (–9.3 ± 4.1 in survivors vs –13.1 ± 4.4, respectively; P = 0.001). SAVE score discrimination was adequate (c = 0.77; 95% confidence interval 0.69-0.86; P < 0.001). SAVE score calibration was limited, as observed survival rates for risk classes II-V were higher in our cohort (II: 67% vs 58%; III: 78% vs 42%; IV: 61% vs 30%; and V: 29% vs 18%). Conclusions The SAVE score underestimates survival in a contemporary North American cohort of adult patients with cardiogenic shock. Its inaccurate performance could lead to denying ECMO support to patients deemed to be too high risk. Further studies are needed to validate additional predictive models for patients requiring VA-ECMO.
Collapse
Affiliation(s)
- Faizan Amin
- Peter Munk Cardiac Centre, Toronto, Ontario, Canada.,Ted Roger's Center for Heart Research, Toronto, Ontario, Canada
| | | | - Mosaad Alhussein
- Peter Munk Cardiac Centre, Toronto, Ontario, Canada.,Ted Roger's Center for Heart Research, Toronto, Ontario, Canada
| | - Juan Duero Posada
- Peter Munk Cardiac Centre, Toronto, Ontario, Canada.,Ted Roger's Center for Heart Research, Toronto, Ontario, Canada
| | | | | | - Eddy Fan
- Interdepartmental Division of Critical Care Medicine and Institute for Health Policy, Management and Evaluation, University of Toronto, Toronto, Ontario, Canada.,University Health Network, Toronto, Ontario, Canada
| | - Heather Ross
- Peter Munk Cardiac Centre, Toronto, Ontario, Canada.,Ted Roger's Center for Heart Research, Toronto, Ontario, Canada
| | - Vivek Rao
- Peter Munk Cardiac Centre, Toronto, Ontario, Canada
| | - Ana Carolina Alba
- Peter Munk Cardiac Centre, Toronto, Ontario, Canada.,Ted Roger's Center for Heart Research, Toronto, Ontario, Canada
| | - Filio Billia
- Peter Munk Cardiac Centre, Toronto, Ontario, Canada.,Ted Roger's Center for Heart Research, Toronto, Ontario, Canada
| |
Collapse
|
11
|
Lüsebrink E, Stremmel C, Stark K, Joskowiak D, Czermak T, Born F, Kupka D, Scherer C, Orban M, Petzold T, von Samson-Himmelstjerna P, Kääb S, Hagl C, Massberg S, Peterss S, Orban M. Update on Weaning from Veno-Arterial Extracorporeal Membrane Oxygenation. J Clin Med 2020; 9:E992. [PMID: 32252267 PMCID: PMC7230450 DOI: 10.3390/jcm9040992] [Citation(s) in RCA: 49] [Impact Index Per Article: 9.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/21/2020] [Revised: 03/18/2020] [Accepted: 03/27/2020] [Indexed: 01/14/2023] Open
Abstract
Venoarterial extracorporeal membrane oxygenation (VA-ECMO) provides temporary cardiac and respiratory support and has emerged as an established salvage intervention for patients with hemodynamic compromise or shock. It is thereby used as a bridge to recovery, bridge to permanent ventricular assist devices, bridge to transplantation, or bridge to decision. However, weaning from VA-ECMO differs between centers, and information about standardized weaning protocols are rare. Given the high mortality of patients undergoing VA-ECMO treatment, it is all the more important to answer the many questions still remaining unresolved in this field Standardized algorithms are recommended to optimize the weaning process and determine whether the VA-ECMO can be safely removed. Successful weaning as a multifactorial process requires sufficient recovery of myocardial and end-organ function. The patient should be considered hemodynamically stable, although left ventricular function often remains impaired during and after weaning. Echocardiographic and invasive hemodynamic monitoring seem to be indispensable when evaluating biventricular recovery and in determining whether the VA-ECMO can be weaned successfully or not, whereas cardiac biomarkers may not be useful in stratifying those who will recover. This review summarizes the strategies of weaning of VA-ECMO and discusses predictors of successful and poor weaning outcome.
Collapse
Affiliation(s)
- Enzo Lüsebrink
- Intensive Care Unit, Medizinische Klinik und Poliklinik I, Klinikum der Universität München, 81377 Munich, Germany; (E.L.); (C.S.); (K.S.); (T.C.); (D.K.); (C.S.); (M.O.); (T.P.); (S.K.); (S.M.)
- DZHK (German Center for Cardiovascular Research), partner site Munich Heart Alliance, Medizinische Klinik und Poliklinik I, Klinikum der Universität München, 81377 Munich, Germany
| | - Christopher Stremmel
- Intensive Care Unit, Medizinische Klinik und Poliklinik I, Klinikum der Universität München, 81377 Munich, Germany; (E.L.); (C.S.); (K.S.); (T.C.); (D.K.); (C.S.); (M.O.); (T.P.); (S.K.); (S.M.)
- DZHK (German Center for Cardiovascular Research), partner site Munich Heart Alliance, Medizinische Klinik und Poliklinik I, Klinikum der Universität München, 81377 Munich, Germany
| | - Konstantin Stark
- Intensive Care Unit, Medizinische Klinik und Poliklinik I, Klinikum der Universität München, 81377 Munich, Germany; (E.L.); (C.S.); (K.S.); (T.C.); (D.K.); (C.S.); (M.O.); (T.P.); (S.K.); (S.M.)
- DZHK (German Center for Cardiovascular Research), partner site Munich Heart Alliance, Medizinische Klinik und Poliklinik I, Klinikum der Universität München, 81377 Munich, Germany
| | - Dominik Joskowiak
- Department of Cardiac Surgery, University Hospital, LMU Munich, 81377 Munich, Germany; (D.J.); (F.B.); (P.v.S.-H.); (C.H.); (S.P.)
| | - Thomas Czermak
- Intensive Care Unit, Medizinische Klinik und Poliklinik I, Klinikum der Universität München, 81377 Munich, Germany; (E.L.); (C.S.); (K.S.); (T.C.); (D.K.); (C.S.); (M.O.); (T.P.); (S.K.); (S.M.)
- DZHK (German Center for Cardiovascular Research), partner site Munich Heart Alliance, Medizinische Klinik und Poliklinik I, Klinikum der Universität München, 81377 Munich, Germany
| | - Frank Born
- Department of Cardiac Surgery, University Hospital, LMU Munich, 81377 Munich, Germany; (D.J.); (F.B.); (P.v.S.-H.); (C.H.); (S.P.)
| | - Danny Kupka
- Intensive Care Unit, Medizinische Klinik und Poliklinik I, Klinikum der Universität München, 81377 Munich, Germany; (E.L.); (C.S.); (K.S.); (T.C.); (D.K.); (C.S.); (M.O.); (T.P.); (S.K.); (S.M.)
- DZHK (German Center for Cardiovascular Research), partner site Munich Heart Alliance, Medizinische Klinik und Poliklinik I, Klinikum der Universität München, 81377 Munich, Germany
| | - Clemens Scherer
- Intensive Care Unit, Medizinische Klinik und Poliklinik I, Klinikum der Universität München, 81377 Munich, Germany; (E.L.); (C.S.); (K.S.); (T.C.); (D.K.); (C.S.); (M.O.); (T.P.); (S.K.); (S.M.)
- DZHK (German Center for Cardiovascular Research), partner site Munich Heart Alliance, Medizinische Klinik und Poliklinik I, Klinikum der Universität München, 81377 Munich, Germany
| | - Mathias Orban
- Intensive Care Unit, Medizinische Klinik und Poliklinik I, Klinikum der Universität München, 81377 Munich, Germany; (E.L.); (C.S.); (K.S.); (T.C.); (D.K.); (C.S.); (M.O.); (T.P.); (S.K.); (S.M.)
- DZHK (German Center for Cardiovascular Research), partner site Munich Heart Alliance, Medizinische Klinik und Poliklinik I, Klinikum der Universität München, 81377 Munich, Germany
| | - Tobias Petzold
- Intensive Care Unit, Medizinische Klinik und Poliklinik I, Klinikum der Universität München, 81377 Munich, Germany; (E.L.); (C.S.); (K.S.); (T.C.); (D.K.); (C.S.); (M.O.); (T.P.); (S.K.); (S.M.)
- DZHK (German Center for Cardiovascular Research), partner site Munich Heart Alliance, Medizinische Klinik und Poliklinik I, Klinikum der Universität München, 81377 Munich, Germany
| | - Patrick von Samson-Himmelstjerna
- Department of Cardiac Surgery, University Hospital, LMU Munich, 81377 Munich, Germany; (D.J.); (F.B.); (P.v.S.-H.); (C.H.); (S.P.)
| | - Stefan Kääb
- Intensive Care Unit, Medizinische Klinik und Poliklinik I, Klinikum der Universität München, 81377 Munich, Germany; (E.L.); (C.S.); (K.S.); (T.C.); (D.K.); (C.S.); (M.O.); (T.P.); (S.K.); (S.M.)
- DZHK (German Center for Cardiovascular Research), partner site Munich Heart Alliance, Medizinische Klinik und Poliklinik I, Klinikum der Universität München, 81377 Munich, Germany
| | - Christian Hagl
- Department of Cardiac Surgery, University Hospital, LMU Munich, 81377 Munich, Germany; (D.J.); (F.B.); (P.v.S.-H.); (C.H.); (S.P.)
| | - Steffen Massberg
- Intensive Care Unit, Medizinische Klinik und Poliklinik I, Klinikum der Universität München, 81377 Munich, Germany; (E.L.); (C.S.); (K.S.); (T.C.); (D.K.); (C.S.); (M.O.); (T.P.); (S.K.); (S.M.)
- DZHK (German Center for Cardiovascular Research), partner site Munich Heart Alliance, Medizinische Klinik und Poliklinik I, Klinikum der Universität München, 81377 Munich, Germany
| | - Sven Peterss
- Department of Cardiac Surgery, University Hospital, LMU Munich, 81377 Munich, Germany; (D.J.); (F.B.); (P.v.S.-H.); (C.H.); (S.P.)
| | - Martin Orban
- Intensive Care Unit, Medizinische Klinik und Poliklinik I, Klinikum der Universität München, 81377 Munich, Germany; (E.L.); (C.S.); (K.S.); (T.C.); (D.K.); (C.S.); (M.O.); (T.P.); (S.K.); (S.M.)
- DZHK (German Center for Cardiovascular Research), partner site Munich Heart Alliance, Medizinische Klinik und Poliklinik I, Klinikum der Universität München, 81377 Munich, Germany
| |
Collapse
|
12
|
Lorusso R, Raffa GM, Alenizy K, Sluijpers N, Makhoul M, Brodie D, McMullan M, Wang IW, Meani P, MacLaren G, Kowalewski M, Dalton H, Barbaro R, Hou X, Cavarocchi N, Chen YS, Thiagarajan R, Alexander P, Alsoufi B, Bermudez CA, Shah AS, Haft J, D'Alessandro DA, Boeken U, Whitman GJR. Structured review of post-cardiotomy extracorporeal membrane oxygenation: part 1-Adult patients. J Heart Lung Transplant 2019; 38:1125-1143. [PMID: 31522913 PMCID: PMC8152367 DOI: 10.1016/j.healun.2019.08.014] [Citation(s) in RCA: 82] [Impact Index Per Article: 13.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/22/2018] [Revised: 07/21/2019] [Accepted: 08/05/2019] [Indexed: 01/25/2023] Open
Abstract
Cardiogenic shock, cardiac arrest, acute respiratory failure, or a combination of such events, are all potential complications after cardiac surgery which lead to high mortality. Use of extracorporeal temporary cardio-circulatory and respiratory support for progressive clinical deterioration can facilitate bridging the patient to recovery or to more durable support. Over the last decade, extracorporeal membrane oxygenation (ECMO) has emerged as the preferred temporary artificial support system in such circumstances. Many factors have contributed to widespread ECMO use, including the relative ease of implantation, effectiveness, versatility, low cost relative to alternative devices, and potential for full, not just partial circulatory support. While there have been numerous publications detailing the short and midterm outcomes of ECMO support, specific reports about post-cardiotomy ECMO (PC-ECMO), are limited, single-center experiences. Etiology of cardiorespiratory failure leading to ECMO implantation, associated ECMO complications, and overall patient outcomes may be unique to the PC-ECMO population. Despite the rise in PC-ECMO use over the past decade, short-term survival has not improved. This report, therefore, aims to present a comprehensive overview of the literature with respect to the prevalence of ECMO use, patient characteristics, ECMO management, and in-hospital and early post-discharge patient outcomes for those treated for post-cardiotomy heart, lung, or heart-lung failure.
Collapse
Affiliation(s)
- Roberto Lorusso
- Cardio-Thoracic Surgery Department, Heart & Vascular Centre, Maastricht University Medical Centre, Maastricht, Netherlands.
| | - Giuseppe Maria Raffa
- Department for the Treatment and Study of Cardiothoracic Diseases and Cardiothoracic Transplantation, IRCCS-ISMETT (Istituto Mediterraneo per I Trapianti e Terapie ad alta specializzazione), Palermo, Italy
| | - Khalid Alenizy
- Cardio-Thoracic Surgery Department, Heart & Vascular Centre, Maastricht University Medical Centre, Maastricht, Netherlands
| | - Niels Sluijpers
- Cardio-Thoracic Surgery Department, Heart & Vascular Centre, Maastricht University Medical Centre, Maastricht, Netherlands
| | - Maged Makhoul
- Cardio-Thoracic Surgery Department, Heart & Vascular Centre, Maastricht University Medical Centre, Maastricht, Netherlands
| | - Daniel Brodie
- Center for Acute Respiratory Care, Columbia University college of Physicians & Surgeon/New Yor Presbyterian Hospital, New York, New York
| | - Mike McMullan
- Cardiac Surgery Unit, Seattle Children Hospital, Seattle, Washington
| | - I-Wen Wang
- Cardiac Transplantation and Mechanical Circulatory Support Unit, Indiana University School of Medicine, Health Methodist Hospital, Indianapolis, Indiana
| | - Paolo Meani
- Heart & Vascular Centre, Cardiology Department, Maastricht University Medical Centre, Maastricht, Netherlands
| | - Graeme MacLaren
- Cardiothoracic Intensive Care Unit, National University, Singapore, Singapore
| | - Mariusz Kowalewski
- Department of Cardiac Surgery, Antoni Jurasz Memorial University Hospital, Bydgoszcz, Poland
| | - Heidi Dalton
- I.N.O.V.A. Fairfax Medical Centre, Adult and Pediatric ECMO Service, Falls Church, Virginia
| | - Ryan Barbaro
- Division of Pediatric Critical Care and Child Health Evaluation and Research Unit, Ann Arbor, Michigan
| | - Xiaotong Hou
- Center for Cardiac Intensive Care, Beijing Anzhen Hospital, Capital Medical University, Beijing, China
| | - Nicholas Cavarocchi
- Surgical Cardiac Care Unit, Thomas Jefferson University Hospital, Philadelphia, Pennsylvania
| | - Yih-Sharng Chen
- Cardiovascular Surgery & Pediatric Cardiovascular Surgery, National Taiwan University Hospital, Taipei, Taiwan
| | - Ravi Thiagarajan
- Department of Cardiology, Boston Children's Hospital; Department of Pediatrics, Harvard Medical School, Boston, Massachusetts
| | - Peta Alexander
- Department of Cardiology, Boston Children's Hospital; Department of Pediatrics, Harvard Medical School, Boston, Massachusetts
| | - Bahaaldin Alsoufi
- Department of Cardiovascular and Thoracic Surgery, University of Louisville School of Medicine, Norton Children's Hospital, Louisville, Kentucky
| | | | - Ashish S Shah
- Department of Cardiac Surgery, Vanderbilt University Medical Center, Nashville, Tennessee
| | - Jonathan Haft
- Section of Cardiac Surgery, University of Michigan, Ann Arbor, Michigan
| | - David A D'Alessandro
- Cardio-Thoracic Surgery Department, Massachusetts Medical Centre, Boston, Massachusetts
| | - Udo Boeken
- Cardiovascular Surgery Unit, University of Düsseldorf, Düsseldorf, Germany
| | - Glenn J R Whitman
- Cardiovascular Surgery Intensive Care Unit, Johns Hopkins Hospital, Baltimore, Maryland
| |
Collapse
|
13
|
In Vivo Effects of Neostigmine and Physostigmine on Neutrophil Functions and Evaluation of Acetylcholinesterase and Butyrylcholinesterase as Inflammatory Markers during Experimental Sepsis in Rats. Mediators Inflamm 2019; 2019:8274903. [PMID: 30804708 PMCID: PMC6360579 DOI: 10.1155/2019/8274903] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/31/2018] [Revised: 09/27/2018] [Accepted: 11/26/2018] [Indexed: 12/17/2022] Open
Abstract
Introduction Recent studies have shown that acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) may serve as important diagnostic and therapeutic targets in sepsis. Since polymorphonuclear neutrophils (PMNs) play a pivotal role in the early phase of sepsis, we evaluated the potential therapeutic effects of cholinesterase inhibitors on PMN functions during cecal ligation and puncture- (CLP-) induced sepsis and investigated the roles of AChE and BChE as inflammatory markers under standardized experimental conditions. Methods Sham surgery or CLP was performed in male Wistar rats (n = 60). Animals were randomized into four groups: physostigmine, 100 μg/kg; neostigmine, 75 μg/kg; 0.9% saline (control group); and sham group, each applied four times over 24 h. The levels of reactive oxygen species (ROS) production and CD11b/CD62l expression were quantified by flow cytometry at t = 0, 6, 15, 20, and 24 h. Blood gas analysis as well as AChE and BChE activity levels was measured by validated point-of-care measurements. Clinical scores and survival times were determined. Results CLP induced a significant increase in ROS production and CD11b upregulation by rat PMNs. Treatment with physostigmine or neostigmine significantly reduced ROS production and CD11b upregulation by PMNs 20 h after CLP induction. In physostigmine-treated animals, survival times were significantly improved compared to the control animals, but not in neostigmine-treated animals. While AChE activity significantly decreased in the control animals at t > 6 h, AChE activity did not change in the sham group. BChE activity decreased at t > 20 h in the control animals. Conclusion While AChE activity may serve as an acute inflammatory marker, BChE activity shows a delayed decrease. Administration of centrally acting physostigmine in CLP-induced sepsis in rats has protective effects on PMN functions and improves survival times, which may be of interest in clinical practice.
Collapse
|
14
|
Distelmaier K, Roth C, Schrutka L, Binder C, Steinlechner B, Heinz G, Lang IM, Maurer G, Koinig H, Niessner A, Hülsmann M, Speidl W, Goliasch G. Beneficial effects of levosimendan on survival in patients undergoing extracorporeal membrane oxygenation after cardiovascular surgery. Br J Anaesth 2018; 117:52-8. [PMID: 27317704 DOI: 10.1093/bja/aew151] [Citation(s) in RCA: 59] [Impact Index Per Article: 8.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 03/16/2016] [Indexed: 11/13/2022] Open
Abstract
BACKGROUND The impact of levosimendan treatment on clinical outcome in patients undergoing extracorporeal membrane oxygenation (ECMO) support after cardiovascular surgery is unknown. We hypothesized that the beneficial effects of levosimendan might improve survival when adequate end-organ perfusion is ensured by concomitant ECMO therapy. We therefore studied the impact of levosimendan treatment on survival and failure of ECMO weaning in patients after cardiovascular surgery. METHODS We enrolled a total of 240 patients undergoing veno-arterial ECMO therapy after cardiovascular surgery at a university-affiliated tertiary care centre into our observational single-centre registry. RESULTS During a median follow-up period of 37 months (interquartile range 19-67 months), 65% of patients died. Seventy-five per cent of patients received levosimendan treatment within the first 24 h after initiation of ECMO therapy. Cox regression analysis showed an association between levosimendan treatment and successful ECMO weaning [adjusted hazard ratio (HR) 0.41; 95% confience interval (CI) 0.22-0.80; P=0.008], 30 day mortality (adjusted HR 0.52; 95% CI 0.30-0.89; P=0.016), and long-term mortality (adjusted HR 0.64; 95% CI 0.42-0.98; P=0.04). CONCLUSIONS These data suggest an association between levosimendan treatment and improved short- and long-term survival in patients undergoing ECMO support after cardiovascular surgery.
Collapse
Affiliation(s)
| | - C Roth
- Department of Internal Medicine II
| | | | - C Binder
- Department of Internal Medicine II
| | - B Steinlechner
- Division of Cardiothoracic and Vascular Anaesthesia and Intensive Care Medicine, Medical University of Vienna, Waehringer Guertel 18-20, A-1090 Vienna, Austria
| | - G Heinz
- Department of Internal Medicine II
| | - I M Lang
- Department of Internal Medicine II
| | - G Maurer
- Department of Internal Medicine II
| | - H Koinig
- Department of Anaesthesia and Intensive Care Medicine, University Hospital Krems, Karl Landsteiner University of Health Sciences, Krems, Austria
| | | | | | - W Speidl
- Department of Internal Medicine II
| | | |
Collapse
|
15
|
A Sustained Reduction in Serum Cholinesterase Enzyme Activity Predicts Patient Outcome following Sepsis. Mediators Inflamm 2018; 2018:1942193. [PMID: 29853783 PMCID: PMC5949165 DOI: 10.1155/2018/1942193] [Citation(s) in RCA: 32] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/25/2018] [Accepted: 03/19/2018] [Indexed: 12/29/2022] Open
Abstract
Early sepsis identification is of paramount importance for an effective therapy and the patient outcome; however, a suitable prognostic biomarker is lacking. Anti-inflammatory nonneuronal cholinergic signaling modulates the magnitude of an immune response. Serum cholinesterase (BChE), an enzyme that hydrolyzes acetylcholine, plays an important role during inflammatory response and serves as an accurate index of cholinergic activity. BChE activity was measured in septic patients using a point-of-care system, and levels of conventional inflammatory markers and the disease severity scores were obtained. We observed a strong, sustained reduction in BChE activity in patients who died within a 90-day observation period, as compared to survivors. Reduced BChE activity when measured at the ICU admission effectively differentiated between the 90-day survivor and the nonsurvivor patient groups. We estimated a critical BChE level of 1.661 kU/L (CI 0.5–0.8, 94% sensitivity, 48% specificity, AUC 0.7) to best predict patient outcome providing a benchmark criterion for early detection of potentially fatal sepsis measured at the admission. This finding suggests that the BChE activity, used in combination with the laboratory tests, clinical examination, and the disease severity scoring, could serve to identify high-risk patients at the ICU admission, the most critical time point in the sepsis treatment.
Collapse
|
16
|
Freundt M, Lunz D, Philipp A, Panholzer B, Lubnow M, Friedrich C, Rupprecht L, Hirt S, Haneya A. Impact of dynamic changes of elevated bilirubin on survival in patients on veno-arterial extracorporeal life support for acute circulatory failure. PLoS One 2017; 12:e0184995. [PMID: 29049294 PMCID: PMC5648125 DOI: 10.1371/journal.pone.0184995] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/20/2017] [Accepted: 09/05/2017] [Indexed: 12/20/2022] Open
Abstract
Aims Veno-arterial extracorporeal life support (ECLS) is an established method to stabilize acute circulatory failure. Parameters and data on when to ideally wean circulatory support are limited. Bilirubin is a marker of end-organ damage. Therefore, the purpose of this large study was to evaluate the impact of dynamic changes of elevated bilirubin levels on survival in patients on ECLS. Methods and results We reviewed 502 consecutive cases of ECLS from 2007 to 2015. Bilirubin levels were recorded before implantation and until six days after explantation. Dynamic bilirubin changes, and hemodynamic and laboratory outcome parameters were compared in survivors and nonsurvivors. Reason for ECLS implantation was cardiac arrest with ongoing resuscitation in 230 (45.8%), low cardiac output in 174 (34.7%) and inability to wean off cardiopulmonary bypass in 98 (19.5%) patients. 307 (61.2%) patients were weaned off ECLS, however, 206 (41.0%) survived. Mean duration of ECLS was 3 (2–6) days, and survivors received significantly longer ECLS (5 vs 3 days, p < 0.001). Survivors had significantly lower baseline bilirubin levels (p = 0.003). Bilirubin started to rise from day 2 in all patients. In survivors, bilirubin levels had trended down on the day of ECLS explantation and stayed at an acceptable level. However, in weaned patients who did not survive and patients who died on ECLS bilirubin levels continued to rise during the recorded period. Conclusion ECLS support improves survival in patients with acute circulatory failure. Down trending bilirubin levels on veno-arterial ECLS indicate improved chances of successful weaning and survival in hemodynamically stable patients.
Collapse
Affiliation(s)
- Miriam Freundt
- Dept. of Cardiothoracic Surgery, University Medical Center of Regensburg, Regensburg, Germany
| | - Dirk Lunz
- Dept. of Anesthesiology and Critical Care, University Medical Center of Regensburg, Regensburg, Germany
| | - Alois Philipp
- Dept. of Cardiothoracic Surgery, University Medical Center of Regensburg, Regensburg, Germany
| | - Bernd Panholzer
- Dept. of Cardiovascular Surgery, University of Schleswig-Holstein, Campus Kiel, Kiel, Germany
| | - Matthias Lubnow
- Dept. of Internal Medicine II, University Medical Center of Regensburg, Regensburg, Germany
| | - Christine Friedrich
- Dept. of Cardiovascular Surgery, University of Schleswig-Holstein, Campus Kiel, Kiel, Germany
| | - Leopold Rupprecht
- Dept. of Cardiothoracic Surgery, University Medical Center of Regensburg, Regensburg, Germany
| | - Stephan Hirt
- Dept. of Cardiothoracic Surgery, University Medical Center of Regensburg, Regensburg, Germany
| | - Assad Haneya
- Dept. of Cardiothoracic Surgery, University Medical Center of Regensburg, Regensburg, Germany
- Dept. of Cardiovascular Surgery, University of Schleswig-Holstein, Campus Kiel, Kiel, Germany
- * E-mail:
| |
Collapse
|
17
|
Bartko PE, Wiedemann D, Schrutka L, Binder C, Santos-Gallego CG, Zuckermann A, Steinlechner B, Koinig H, Heinz G, Niessner A, Zimpfer D, Laufer G, Lang IM, Distelmaier K, Goliasch G. Impact of Right Ventricular Performance in Patients Undergoing Extracorporeal Membrane Oxygenation Following Cardiac Surgery. J Am Heart Assoc 2017; 6:JAHA.116.005455. [PMID: 28754654 PMCID: PMC5586414 DOI: 10.1161/jaha.116.005455] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/16/2022]
Abstract
BACKGROUND Extracorporeal membrane oxygenation following cardiac surgery safeguards end-organ oxygenation but unfavorably alters cardiac hemodynamics. Along with the detrimental effects of cardiac surgery to the right heart, this might impact outcome, particularly in patients with preexisting right ventricular (RV) dysfunction. We sought to determine the prognostic impact of RV function and to improve established risk-prediction models in this vulnerable patient cohort. METHODS AND RESULTS Of 240 patients undergoing extracorporeal membrane oxygenation support following cardiac surgery, 111 had echocardiographic examinations at our institution before implantation of extracorporeal membrane oxygenation and were thus included. Median age was 67 years (interquartile range 60-74), and 74 patients were male. During a median follow-up of 27 months (interquartile range 16-63), 75 patients died. Fifty-one patients died within 30 days, 75 during long-term follow-up (median follow-up 27 months, minimum 5 months, maximum 125 months). Metrics of RV function were the strongest predictors of outcome, even stronger than left ventricular function (P<0.001 for receiver operating characteristics comparisons). Specifically, RV free-wall strain was a powerful predictor univariately and after adjustment for clinical variables, Simplified Acute Physiology Score-3, tricuspid regurgitation, surgery type and duration with adjusted hazard ratios of 0.41 (95%CI 0.24-0.68; P=0.001) for 30-day mortality and 0.48 (95%CI 0.33-0.71; P<0.001) for long-term mortality for a 1-SD (SD=-6%) change in RV free-wall strain. Combined assessment of the additive EuroSCORE and RV free-wall strain improved risk classification by a net reclassification improvement of 57% for 30-day mortality (P=0.01) and 56% for long-term mortality (P=0.02) compared with the additive EuroSCORE alone. CONCLUSIONS RV function is strongly linked to mortality, even after adjustment for baseline variables and clinical risk scores. RV performance improves established risk prediction models for short- and long-term mortality.
Collapse
Affiliation(s)
- Philipp E Bartko
- Department of Internal Medicine II, Medical University of Vienna, Austria.,Center for Cardiovascular Medicine, Medical University of Vienna, Austria.,Massachusetts General Hospital, Harvard Medical School, Boston, MA
| | - Dominik Wiedemann
- Department of Cardiac Surgery, Medical University of Vienna, Austria.,Center for Cardiovascular Medicine, Medical University of Vienna, Austria
| | - Lore Schrutka
- Department of Internal Medicine II, Medical University of Vienna, Austria.,Center for Cardiovascular Medicine, Medical University of Vienna, Austria
| | - Christina Binder
- Department of Internal Medicine II, Medical University of Vienna, Austria.,Center for Cardiovascular Medicine, Medical University of Vienna, Austria
| | | | - Andreas Zuckermann
- Department of Cardiac Surgery, Medical University of Vienna, Austria.,Center for Cardiovascular Medicine, Medical University of Vienna, Austria
| | - Barbara Steinlechner
- Division of Cardiothoracic and Vascular Anaesthesia and Intensive Care Medicine, Medical University of Vienna, Austria
| | - Herbert Koinig
- Department of Anaesthesia and Intensive Care Medicine, Karl Landsteiner University of Health Sciences University Hospital Krems, Krems, Austria
| | - Gottfried Heinz
- Department of Internal Medicine II, Medical University of Vienna, Austria.,Center for Cardiovascular Medicine, Medical University of Vienna, Austria
| | - Alexander Niessner
- Department of Internal Medicine II, Medical University of Vienna, Austria.,Center for Cardiovascular Medicine, Medical University of Vienna, Austria
| | - Daniel Zimpfer
- Department of Cardiac Surgery, Medical University of Vienna, Austria.,Center for Cardiovascular Medicine, Medical University of Vienna, Austria
| | - Günther Laufer
- Department of Cardiac Surgery, Medical University of Vienna, Austria.,Center for Cardiovascular Medicine, Medical University of Vienna, Austria
| | - Irene M Lang
- Department of Internal Medicine II, Medical University of Vienna, Austria.,Center for Cardiovascular Medicine, Medical University of Vienna, Austria
| | - Klaus Distelmaier
- Department of Internal Medicine II, Medical University of Vienna, Austria .,Center for Cardiovascular Medicine, Medical University of Vienna, Austria
| | - Georg Goliasch
- Department of Internal Medicine II, Medical University of Vienna, Austria.,Center for Cardiovascular Medicine, Medical University of Vienna, Austria
| |
Collapse
|
18
|
John M, Ely EW, Halfkann D, Schoen J, Sedemund-Adib B, Klotz S, Radtke F, Stehr S, Hueppe M. Acetylcholinesterase and butyrylcholinesterase in cardiosurgical patients with postoperative delirium. J Intensive Care 2017; 5:29. [PMID: 28560042 PMCID: PMC5446746 DOI: 10.1186/s40560-017-0224-1] [Citation(s) in RCA: 29] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/25/2017] [Accepted: 05/15/2017] [Indexed: 12/03/2022] Open
Abstract
Background Patients in intensive care units (ICU) are often diagnosed with postoperative delirium; the duration of which has a relevant negative impact on various clinical outcomes. Recent research found a potentially important role of acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) in delirium of critically ill patients on non-surgical ICU or in non-cardiac-surgery patients. We tested the hypothesis that AChE and BChE have an impact on patients after cardiac surgery with postoperative delirium. Methods After obtaining approval from the local ethics committee, this mechanistic study gathered data of all 217 patients included in a randomized controlled trial testing non-pharmacological modifications of care in the cardiac surgical ICU to reduce delirium. Delirium was assessed with the Confusion Assessment Method for the Intensive Care Unit (CAM-ICU) and the Nursing Delirium Screening Scale (Nu-DESC) twice a day for the first 3 days after surgery. Further outcome variables were somatic laboratory parameters and variables regarding surgery, anesthesia, and postsurgical recovery. 10 μl venous or arterial blood was drawn and AChE and BChE were determined with ChE check mobile from Securetec. Results Of 217 patients, 60 (27.6%) developed postsurgical delirium (POD). Patients with POD were older (p = 0.005), had anemia (p = 0.01), and worse kidney function (p = 0.006). Furthermore, these patients had lower intraoperative cerebral saturation (NIRS) (p < 0.001) and higher intraoperative need of catecholamines (p = 0.03). Delirious patients showed more inflammatory response (p < 0.001). AChE and BChE values were mainly inside the norm. Patients with values outside the norm did not have POD more often than others. Regarding AChE and BChE patients did not differ in having delirium or not (p > 0.10). Conclusions Postoperative measurement of AChE and BChE did not discern between patients with and without POD. The effect of the cardiac surgical procedure on AChE and BChE remains unclear. Further studies with patients in cardiac surgery are needed to evaluate a possible combination of delirium and the cholinergic transmitter system. There might be possible interactions with AChE/BChE and blood products and the use of cardiopulmonary bypass, which should be investigated more intensively. Trial registration German Clinical Trials Register, DRKS00006217
Collapse
Affiliation(s)
- Mira John
- Clinic for Anaesthesiology and Intensive-Care Medicine, UKSH Campus Luebeck, Ratzeburger Allee 160, 23538 Luebeck, Germany
| | - E Wesley Ely
- Pulmonary and Critical Care Medicine, Vanderbilt University, Nashville, Tennessee USA.,Geriatric Research Education Clinical Center (GRECC) of the Tennessee Valley Veterans Administration, Nashville, Tennessee USA
| | - Dorothee Halfkann
- Clinic for Anaesthesiology and Intensive-Care Medicine, UKSH Campus Luebeck, Ratzeburger Allee 160, 23538 Luebeck, Germany
| | - Julika Schoen
- Clinic for Anaesthesiology and Intensive-Care Medicine, UKSH Campus Luebeck, Ratzeburger Allee 160, 23538 Luebeck, Germany
| | - Beate Sedemund-Adib
- Clinic for Anaesthesiology and Intensive-Care Medicine, UKSH Campus Luebeck, Ratzeburger Allee 160, 23538 Luebeck, Germany
| | - Stefan Klotz
- Department of Cardiac and Thoracic Vascular Surgery, UKSH Campus Luebeck, Luebeck, Germany
| | - Finn Radtke
- Clinic for Anaesthesiology and Operative Intensive-Care Medicine, Charité University Hospital Berlin, Berlin, Germany
| | - Sebastian Stehr
- Clinic for Anaesthesiology and Intensive-Care Medicine, UKSH Campus Luebeck, Ratzeburger Allee 160, 23538 Luebeck, Germany
| | - Michael Hueppe
- Clinic for Anaesthesiology and Intensive-Care Medicine, UKSH Campus Luebeck, Ratzeburger Allee 160, 23538 Luebeck, Germany
| |
Collapse
|
19
|
Abstract
Blood-based biomarkers are important in the detection of the disease and in the assessment of responses to therapy. In this study, butyrylcholinesterase was evaluated as a potential biomarker in newly diagnosed neuroblastoma (NB) patients at diagnosis and longitudinally during treatment. Plasma butyrylcholinesterase activities in age-matched and sex-matched children were used as controls. Pretreatment butyrylcholinesterase levels in NB subjects are on an average 2 times lower than butyrylcholinesterase levels in healthy subjects. Significantly, butyrylcholinesterase activities are ∼40% lower in MYCN-amplified as compared with nonamplified disease. As the course of chemotherapy progresses, butyrylcholinesterase activities recover and normalize to control values. The evident response to treatment indicates that plasma butyrylcholinesterase is a good biomarker of tumor response to therapy. Depressed butyrylcholinesterase levels in NB subjects are not caused by hepatic deficits suggesting a specific role for butyrylcholinesterase in NB. Further examination of the mechanism of altered butyrylcholinesterase production require an animal model that best approximates human condition. Studies in mice show that murine NB allografts significantly reduce butyrylcholinesterase activity in plasma. This finding correlates with changes observed in NB patients. In contrast, human NB xenografts produce the opposite effect, that is, butyrylcholinesterase plasma levels rise as the xenograft size increases. In the absence of any liver damage, dissimilarities between butyrylcholinesterase production in murine and human NB models suggest species-specific signaling pathways. This disparity also suggests that human NB xenograft mouse models do not approximate the human disease.
Collapse
|
20
|
Pavo N, Raderer M, Goliasch G, Wurm R, Strunk G, Cho A, Novak JF, Gisslinger H, Steger GG, Hejna M, Köstler W, Zöchbauer-Müller S, Marosi C, Kornek G, Auerbach L, Schneider ST, Parschalk B, Scheithauer W, Pirker R, Kiesewetter B, Pacher R, Zielinski C, Hülsmann M. Subclinical involvement of the liver is associated with prognosis in treatment naïve cancer patients. Oncotarget 2017; 8:81250-81260. [PMID: 29113384 PMCID: PMC5655279 DOI: 10.18632/oncotarget.17131] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/29/2016] [Accepted: 04/04/2017] [Indexed: 12/18/2022] Open
Abstract
Background Routinely tested liver biomarkers as alanine aminotransferase (ALT), aspartate aminotransferase (AST), γ-glutamyltransferase (GGT), butyryl-cholinesterase (BChE), albumin and bilirubin are altered in distinct malignancies and hepatic metastases. This study aimed to investigate whether all liver parameters have the ability to predict long-term mortality in treatment naïve cancer patients but without a malignant hepatic involvement. Methods We prospectively enrolled 555 consecutive patients with primary diagnosis of cancer without prior anticancer therapy. BChE, albumin, AST, ALT, GGT and bilirubin as well as the inflammatory makers C-reactive protein (CRP), serum amyloid A (SAA) and interleukin-6 (IL-6) were determined. All-cause mortality was defined as primary endpoint. Results During a median follow-up of 25 (IQR16-31) months 186 (34%) patients died. All liver parameters were significantly associated with all-cause mortality (p < 0.001 for all). However, for patients without a malignant primary or secondary hepatic involvement (82%) only the functional parameters BChE and albumin remained significantly associated with the primary endpoint (crude HR per 1-IQR increase 0.61, 95%CI:0.49-0.77; p < 0.001 for BChE and 0.58, 95%CI:0.47-0.70; p < 0.001 for albumin). This e ect was persistent after multivariate adjustment (adj.HR per 1-IQR increase 0.65, 95%CI:0.50-0.86; p = 0.002 for BChE and 0.63, 95%CI:0.50-0.79; p < 0.001 for albumin). BChE and albumin correlated inversely with CRP (r = -0.21, p < 0.001 and r = -0.36, p < 0.001), SAA (r = -0.19, p < 0.001 and r = -0.33, p < 0.001) and IL-6 (r = -0.13, p = 0.009 and r = -0.17, p = 0.001). Conclusions Decreased serum BChE and albumin levels are associated with increased all-cause mortality in treatment-naïve cancer patients without a manifest malignant hepatic involvement irrespective of tumor entity or stage. This association may reflect progressing systemic inflammation and metabolic derangement with subclinical involvement of the liver.
Collapse
Affiliation(s)
- Noemi Pavo
- Department of Internal Medicine II, Division of Cardiology, Medical University of Vienna, Vienna, Austria
| | - Markus Raderer
- Department of Internal Medicine I, Division of Oncology and Hematology, Medical University of Vienna, Vienna, Austria
| | - Georg Goliasch
- Department of Internal Medicine II, Division of Cardiology, Medical University of Vienna, Vienna, Austria
| | - Raphael Wurm
- Department of Internal Medicine II, Division of Cardiology, Medical University of Vienna, Vienna, Austria
| | | | - Anna Cho
- Department of Internal Medicine II, Division of Cardiology, Medical University of Vienna, Vienna, Austria
| | - Johannes F Novak
- Department of Internal Medicine II, Division of Cardiology, Medical University of Vienna, Vienna, Austria
| | - Heinz Gisslinger
- Department of Internal Medicine I, Division of Oncology and Hematology, Medical University of Vienna, Vienna, Austria
| | - Günther G Steger
- Department of Internal Medicine I, Division of Oncology and Hematology, Medical University of Vienna, Vienna, Austria
| | - Michael Hejna
- Department of Internal Medicine I, Division of Oncology and Hematology, Medical University of Vienna, Vienna, Austria
| | - Wolfgang Köstler
- Department of Internal Medicine I, Division of Oncology and Hematology, Medical University of Vienna, Vienna, Austria
| | - Sabine Zöchbauer-Müller
- Department of Internal Medicine I, Division of Oncology and Hematology, Medical University of Vienna, Vienna, Austria
| | - Christine Marosi
- Department of Internal Medicine I, Division of Oncology and Hematology, Medical University of Vienna, Vienna, Austria
| | - Gabriela Kornek
- Department of Internal Medicine I, Division of Oncology and Hematology, Medical University of Vienna, Vienna, Austria
| | - Leo Auerbach
- Department of Gynaecology, Medical University of Vienna, Vienna, Austria
| | - Sven Thorben Schneider
- Department of Otorhinolaryngology - Head and Neck Surgery, Medical University of Vienna, Vienna, Austria
| | - Bernhard Parschalk
- Department of Otorhinolaryngology - Head and Neck Surgery, Medical University of Vienna, Vienna, Austria
| | - Werner Scheithauer
- Department of Internal Medicine I, Division of Oncology and Hematology, Medical University of Vienna, Vienna, Austria
| | - Robert Pirker
- Department of Internal Medicine I, Division of Oncology and Hematology, Medical University of Vienna, Vienna, Austria
| | - Barbara Kiesewetter
- Department of Internal Medicine I, Division of Oncology and Hematology, Medical University of Vienna, Vienna, Austria
| | - Richard Pacher
- Department of Internal Medicine II, Division of Cardiology, Medical University of Vienna, Vienna, Austria
| | - Christoph Zielinski
- Department of Internal Medicine I, Division of Oncology and Hematology, Medical University of Vienna, Vienna, Austria
| | - Martin Hülsmann
- Department of Internal Medicine II, Division of Cardiology, Medical University of Vienna, Vienna, Austria
| |
Collapse
|
21
|
Bitzinger DI, Gruber M, Tümmler S, Michels B, Bundscherer A, Hopf S, Trabold B, Graf BM, Zausig YA. Species- and concentration-dependent differences of acetyl- and butyrylcholinesterase sensitivity to physostigmine and neostigmine. Neuropharmacology 2016; 109:1-6. [DOI: 10.1016/j.neuropharm.2016.01.005] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/14/2015] [Revised: 12/24/2015] [Accepted: 01/03/2016] [Indexed: 11/29/2022]
|
22
|
Urinary Output Predicts Survival in Patients Undergoing Extracorporeal Membrane Oxygenation Following Cardiovascular Surgery. Crit Care Med 2016; 44:531-8. [PMID: 26562346 DOI: 10.1097/ccm.0000000000001421] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Abstract
OBJECTIVES Extracorporeal membrane oxygenation represents a valuable and rapidly evolving therapeutic option in patients with severe heart or lung failure following cardiovascular surgery. However, survival remains poor and accurate risk stratification challenging. Therefore, we evaluated the predictive value of urinary output within 24 hours after extracorporeal membrane oxygenation initiation on mortality in patients undergoing venoarterial extracorporeal membrane oxygenation support following cardiovascular surgery and aimed to improve established risk prediction models. DESIGN Single-center, observational registry. SETTING University-affiliated tertiary care center. PATIENTS We included 205 patients undergoing veno-arterial extracorporeal membrane oxygenation therapy following cardiovascular surgery at a university-affiliated tertiary-care center into our single-centre registry. INTERVENTIONS None. MEASUREMENTS AND MAIN RESULTS During a median follow-up time of 35 months (interquartile range, 19-69), 64% of patients died. Twenty-four-hour urinary output was the strongest predictor of outcome among renal function variables with an adjusted hazard ratio per 1 SD of 0.55 (95% CI, 0.40-0.76; p < 0.001) for 30-day mortality and of 0.65 (95% CI, 0.53-0.86; p = 0.002) for 2-year long-term mortality. Most remarkably, 24-hour urinary output showed additional prognostic value beyond that achievable with the simplified acute physiology score-3 and sequential organ failure assessment score indicated by improvements in the category-free net reclassification index for 30-day mortality (simplified acute physiology score-3: 36%, p = 0.015; sequential organ failure assessment score: 36%, p = 0.02), as well as for 2-year mortality (simplified acute physiology score-3: 33%, p = 0.02; sequential organ failure assessment score: 43%, p = 0.005). CONCLUSIONS We identified 24-hour urinary output as a strong and easily available predictor of mortality in patients undergoing extracorporeal membrane oxygenation therapy following cardiovascular surgery. Implementation of 24-hour urinary output leads to a substantial improvement of established risk prediction models in this vulnerable patient population. These results are particularly compelling because measurement of urinary output is inexpensive and routinely performed in all critical care units.
Collapse
|
23
|
Roth C, Schrutka L, Binder C, Kriechbaumer L, Heinz G, Lang IM, Maurer G, Koinig H, Steinlechner B, Niessner A, Distelmaier K, Goliasch G. Liver function predicts survival in patients undergoing extracorporeal membrane oxygenation following cardiovascular surgery. CRITICAL CARE : THE OFFICIAL JOURNAL OF THE CRITICAL CARE FORUM 2016; 20:57. [PMID: 26968521 PMCID: PMC4788876 DOI: 10.1186/s13054-016-1242-4] [Citation(s) in RCA: 42] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 11/18/2015] [Accepted: 02/15/2016] [Indexed: 12/21/2022]
Abstract
BACKGROUND Extracorporeal membrane oxygenation (ECMO) represents a valuable and rapidly evolving therapeutic option in patients with severe heart or lung failure following cardiovascular surgery. However, despite significant advances in ECMO techniques and management, prognosis remains poor and accurate risk stratification challenging. We therefore evaluated the predictive value of liver function variables on all-cause mortality in patients undergoing venoarterial ECMO support after cardiovascular surgery. METHODS We included into our single-center registry a total of 240 patients undergoing venoarterial ECMO therapy following cardiovascular surgery at a university-affiliated tertiary care center. RESULTS The median follow-up was 37 months (interquartile range 19-67 months), and a total of 156 patients (65%) died. Alkaline phosphatase and total bilirubin were the strongest predictors for 30-day mortality, with adjusted hazard ratios (HRs) per 1-standard deviation increase of 1.36 (95% confidence interval [CI] 1.10-1.68; P = 0.004) and 1.22 (95% CI 1.07-1.40; P = 0.004), respectively. The observed associations persisted for long-term mortality, with adjusted HRs of 1.27 (95% CI 1.03-1.56; P = 0.023) for alkaline phosphatase and 1.22 (95% CI 1.07-1.39; P = 0.003) for total bilirubin. CONCLUSIONS The present study demonstrates that elevated values of alkaline phosphatase and total bilirubin are sensitive parameters for predicting the short-term and long-term outcomes of ECMO patients.
Collapse
Affiliation(s)
- Christian Roth
- Department of Internal Medicine II, Medical University of Vienna, Vienna, Austria
| | - Lore Schrutka
- Department of Internal Medicine II, Medical University of Vienna, Vienna, Austria
| | - Christina Binder
- Department of Internal Medicine II, Medical University of Vienna, Vienna, Austria
| | - Lukas Kriechbaumer
- University Clinic of Orthopedics, Paracelsus Medical University Salzburg, Salzburg, Austria
| | - Gottfried Heinz
- Department of Internal Medicine II, Medical University of Vienna, Vienna, Austria
| | - Irene M Lang
- Department of Internal Medicine II, Medical University of Vienna, Vienna, Austria
| | - Gerald Maurer
- Department of Internal Medicine II, Medical University of Vienna, Vienna, Austria
| | - Herbert Koinig
- Department of Anesthesia and Intensive Care Medicine, Karl Landsteiner University of Health Sciences, University Hospital Krems, Krems an der Donau, Austria
| | - Barbara Steinlechner
- Division of Cardiothoracic and Vascular Anesthesia and Intensive Care Medicine, Medical University of Vienna, Vienna, Austria
| | - Alexander Niessner
- Department of Internal Medicine II, Medical University of Vienna, Vienna, Austria
| | - Klaus Distelmaier
- Department of Internal Medicine II, Medical University of Vienna, Vienna, Austria.
| | - Georg Goliasch
- Department of Internal Medicine II, Medical University of Vienna, Vienna, Austria
| |
Collapse
|
24
|
The ENCOURAGE mortality risk score and analysis of long-term outcomes after VA-ECMO for acute myocardial infarction with cardiogenic shock. Intensive Care Med 2016; 42:370-378. [DOI: 10.1007/s00134-016-4223-9] [Citation(s) in RCA: 269] [Impact Index Per Article: 29.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/04/2015] [Accepted: 01/10/2016] [Indexed: 12/22/2022]
|
25
|
Schmidt M, Burrell A, Roberts L, Bailey M, Sheldrake J, Rycus PT, Hodgson C, Scheinkestel C, Cooper DJ, Thiagarajan RR, Brodie D, Pellegrino V, Pilcher D. Predicting survival after ECMO for refractory cardiogenic shock: the survival after veno-arterial-ECMO (SAVE)-score. Eur Heart J 2015; 36:2246-56. [DOI: 10.1093/eurheartj/ehv194] [Citation(s) in RCA: 485] [Impact Index Per Article: 48.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/26/2014] [Accepted: 04/29/2015] [Indexed: 11/14/2022] Open
|
26
|
Sulzgruber P, Koller L, Reiberger T, El-Hamid F, Forster S, Rothgerber DJ, Goliasch G, Wojta J, Niessner A. Butyrylcholinesterase predicts cardiac mortality in young patients with acute coronary syndrome. PLoS One 2015; 10:e0123948. [PMID: 25933219 PMCID: PMC4416767 DOI: 10.1371/journal.pone.0123948] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/23/2014] [Accepted: 03/09/2015] [Indexed: 12/31/2022] Open
Abstract
Background The incidence of acute coronary syndrome (ACS) in young people (≤65 years) is continuously rising. While prognostic factors in ACS are well-investigated less attention has been paid to their age-dependent prognostic value and their particular relevance in younger patients. The aim of our study was to assess the age-dependent prognostic impact of butyrylcholinesterase (BChE). Methods Retrospective cohort study including 624 patients with ACS. Patients were stratified by age into equal groups (n = 208) corresponding to “young patients” (45–64 years), "middle-aged patients” (65–84 years) and “old patients” (85–100 years). Cox regression hazard analysis was used to assess the influence of BChE on survival. Results After a mean follow-up time of 4.0 (interquartile range [IQR] 2.0–6.4) years, 154 patients (24.7%) died due to a cardiac cause. In the overall cohort, BChE was indirectly associated with cardiac mortality-free survival (adjusted hazard ratio (HR): 0.70 (95% confidence interval [CI] 0.53–0.93, p = 0.01). The primary-analysis of BChE by age strata showed the strongest effect in the age group 45–64 years with an adjusted HR per 1-SD of 0.28 (95% CI 0.12–0.64, p = 0.003), a weaker association with mortality in middle aged (65–84 years: adjusted HR per 1-SD 0.66 [95% CI: 0.41–1.06], p = 0.087), and no association in older patients (85–100 years: adjusted HR per 1-SD 0.89 [95% CI: 0.58–1.38], p = 0.613). Conclusion BChE is a strong predictor for cardiac mortality specifically in younger patients with ACS aged between 45 and 64 years. No significant association of BChE with cardiac-mortality was detected in other age classes.
Collapse
Affiliation(s)
- Patrick Sulzgruber
- Division of Cardiology, Department of Internal Medicine II, Medical University of Vienna, Vienna, Austria
| | - Lorenz Koller
- Division of Cardiology, Department of Internal Medicine II, Medical University of Vienna, Vienna, Austria
| | - Thomas Reiberger
- Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria
- Edwin L. Steele Laboratory, Dept. of Radiation Oncology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, United States of America
| | - Feras El-Hamid
- Division of Cardiology, Department of Internal Medicine II, Medical University of Vienna, Vienna, Austria
| | - Stefan Forster
- Division of Cardiology, Department of Internal Medicine II, Medical University of Vienna, Vienna, Austria
| | - David-Jonas Rothgerber
- Division of Cardiology, Department of Internal Medicine II, Medical University of Vienna, Vienna, Austria
| | - Georg Goliasch
- Division of Cardiology, Department of Internal Medicine II, Medical University of Vienna, Vienna, Austria
| | - Johann Wojta
- Division of Cardiology, Department of Internal Medicine II, Medical University of Vienna, Vienna, Austria
| | - Alexander Niessner
- Division of Cardiology, Department of Internal Medicine II, Medical University of Vienna, Vienna, Austria
- * E-mail:
| |
Collapse
|
27
|
Reduced serum butyrylcholinesterase activity indicates severe systemic inflammation in critically ill patients. Mediators Inflamm 2015; 2015:274607. [PMID: 25762852 PMCID: PMC4339712 DOI: 10.1155/2015/274607] [Citation(s) in RCA: 41] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/03/2014] [Revised: 12/27/2014] [Accepted: 01/03/2015] [Indexed: 12/29/2022] Open
Abstract
Systemic inflammation is an immune response to a nonspecific insult of either infectious or noninfectious origin and remains a challenge in the intensive care units with high mortality rate. Cholinergic neurotransmission plays an important role in the regulation of the immune response during inflammation. We hypothesized that the activity of butyrylcholinesterase (BChE) might serve as a marker to identify and prognose systemic inflammation. By using a point-of-care-testing (POCT) approach we measured BChE activity in patients with severe systemic inflammation and healthy volunteers. We observed a decreased BChE activity in patients with systemic inflammation, as compared to that of healthy individuals. Furthermore, BChE activity showed an inverse correlation with the severity of the disease. Although hepatic function has previously been found essential for BChE production, we show here that the reduced BChE activity associated with systemic inflammation occurs independently of and is thus not caused by any deficit in liver function in these patients. A POCT approach, used to assess butyrylcholinesterase activity, might further improve the therapy of the critically ill patients by minimizing time delays between the clinical assessment and treatment of the inflammatory process. Hence, assessing butyrylcholinesterase activity might help in early detection of inflammation.
Collapse
|
28
|
Aissaoui N, El-Banayosy A, Combes A. How to wean a patient from veno-arterial extracorporeal membrane oxygenation. Intensive Care Med 2015; 41:902-5. [DOI: 10.1007/s00134-015-3663-y] [Citation(s) in RCA: 98] [Impact Index Per Article: 9.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/06/2015] [Accepted: 01/12/2015] [Indexed: 11/28/2022]
|
29
|
Fan E, Pham T. Extracorporeal Membrane Oxygenation for Severe Acute Respiratory Failure: Yes We Can! (But Should We?). Am J Respir Crit Care Med 2014; 189:1293-5. [DOI: 10.1164/rccm.201404-0711ed] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022] Open
|
30
|
Stephens R, Fan E. Choosing wisely - when to mend a broken heart with ECMO? CRITICAL CARE : THE OFFICIAL JOURNAL OF THE CRITICAL CARE FORUM 2014; 18:112. [PMID: 24602370 PMCID: PMC4059487 DOI: 10.1186/cc13736] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Indexed: 11/15/2022]
Abstract
Refractory cardiac shock in the cardiac surgical intensive care unit confers significant morbidity and mortality. Extracorporeal membrane oxygenation (ECMO) has become a common intervention for refractory cardiogenic shock when other therapies have failed. However, it is difficult to predict who will benefit from this costly, resource-intensive, but potentially life-saving technology. Here, we discuss the utility of a novel biomarker, serum butylcholinesterase, in determining survival in patients supported with ECMO following cardiac surgery.
Collapse
|