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Article ; Online: The Specific Bile Acid Profile of Shock

Lars-Olav Harnisch / Onnen Moerer

Journal of Clinical Medicine, Vol 9, Iss 3844, p

A Hypothesis Generating Appraisal of the Literature

2020 Volume 3844

Abstract: Background: Bile acid synthesis and regulation of metabolism are tightly regulated. In critical illness, these regulations are impaired. Consequently, the physiologic bile acid pattern in serum becomes disturbed and a disease-specific bile acid profile ... ...

Abstract	Background: Bile acid synthesis and regulation of metabolism are tightly regulated. In critical illness, these regulations are impaired. Consequently, the physiologic bile acid pattern in serum becomes disturbed and a disease-specific bile acid profile seems to become evident. Methods: A literature review was performed and trials reporting the broken-down bile acid pattern were condensed with regard to percent differences in bile acid profiles of defined diseases compared to a human control. Results: Ten articles were identified. Most of the studied bile acid profiles differ statistically significant between disease states, furthermore, neither of the reported disease entities show the same broken-down pattern of individual bile acids. Deoxycholic acid (DCA) was found to be decreased in almost all diseases, except for the two shock-states investigated (cardiogenic shock, septic shock) where it was elevated by about 100% compared to the control. Moreover, the pattern of both examined shock-states are very similar, rendering a specific shock-pattern possible, that we argue could eventually maintain or even worsen the pathological state. Conclusion: The specific broken-down bile acid profile of defined diseases might aid in gaining insight into the body’s adaptive reaction and the differential diagnosis, as well as in the therapy of disease states in the early course of the disease.
Keywords	bile acids ; bile acid profile ; critical illness ; shock-pattern ; deoxycholic acid ; Medicine ; R
Subject code	610
Language	English
Publishing date	2020-11-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Hemodynamic profiling by critical care echocardiography could be more accurate than invasive techniques and help identify targets for treatment

Stefan Schmidt / Jana-Katharina Dieks / Michael Quintel / Onnen Moerer

Scientific Reports, Vol 12, Iss 1, Pp 1-

2022 Volume 10

Abstract: Abstract In this prospective observational study, non-invasive critical care echocardiography (CCE) was used to obtain quantitative hemodynamic parameters in 107 intensive care unit (ICU) patients; the parameters were then visualized in a novel web graph ...

Abstract	Abstract In this prospective observational study, non-invasive critical care echocardiography (CCE) was used to obtain quantitative hemodynamic parameters in 107 intensive care unit (ICU) patients; the parameters were then visualized in a novel web graph approach to increase the understanding and impact of CCE abnormalities, as an alternative to thermodilution techniques. Visualizing the CCE hemodynamic data in six-dimensional web graph plots was feasible in almost all ICU patients. In 23.1% of patients, significant tricuspid regurgitation prevented correlation between thermodilution techniques and echocardiographic hemodynamics. Two parameters of longitudinal right ventricular function (TAPSE and S’) did not correlate in ICU patients. Clinical surrogate parameters of hemodynamic compromise did not correlate with measured hemodynamics. 26.2% of the patients with mean arterial pressures above 60 mmHg had cardiac indices (CI) below 2.5 L min−1·m−2. A CI below 2.2 L·min−1·m−2 was associated with a significant ICU survival disadvantage. CCE was feasible in addition or as an alternative to thermodilution techniques for the hemodynamic evaluation of ICU patients. Six-dimensional web graph plots visualized the hemodynamic states and were especially useful in conditions in which thermodilution methods were not reliable. Hemodynamic CCE identified patients with previously unknown low CI, which correlated with a higher ICU mortality.
Keywords	Medicine ; R ; Science ; Q
Subject code	610
Language	English
Publishing date	2022-05-01T00:00:00Z
Publisher	Nature Portfolio
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Case Report

Michael Sobotta / Onnen Moerer / Oliver Gross

Frontiers in Medicine, Vol

Eculizumab and ECMO Rescue Therapy of Severe ARDS in Goodpasture Syndrome

2021 Volume 8

Abstract: Introduction: Goodpasture's syndrome is a life-threatening autoimmune type IV collagen disease characterized by the presence anti–glomerular basement membrane antibodies, rapid progressive glomerulonephritis and/or pulmonary hemorrhage.Methods: Here, we ... ...

Abstract	Introduction: Goodpasture's syndrome is a life-threatening autoimmune type IV collagen disease characterized by the presence anti–glomerular basement membrane antibodies, rapid progressive glomerulonephritis and/or pulmonary hemorrhage.Methods: Here, we describe new therapeutic options, which take recent advances in unraveling Goodpasture's pathogenesis into account.Results: In a 17-year old male, severe Goodpasture's syndrome resulted in acute respiratory distress syndrome (ARDS). Within 1 day after hospital admission, the patient required extracorporeal membrane oxygenation (ECMO). Despite steroid-pulse and plasmapheresis, ARDS further deteriorated. Eleven days after admission, the patient was in a pre-final stage. At last, we decided to block the complement-driven lung damage by Eculizumab. Three days after, lung-failure has stabilized in a way allowing us to initiate Cyclophosphamide-therapy. As mechanical ventilation further triggers Goodpasture-epitope exposure, the patient was taken from pressure support - breathing spontaneously by the help of maintaining ECMO therapy. After a total of 24 days, ECMO could be stopped and pulmonary function further recovered.Conclusions: In conclusion, our findings suggest that life-threatening organ-damage in Goodpasture's syndrome can be halted by Eculizumab as well as by lung-protective early withdrawal from pressure support by the help of ECMO. Both therapeutic options serve as new tools in otherwise hopeless situations to prevent further organ-damage and to gain time until the established immunosuppressive therapy works in otherwise lethal autoimmune-diseases.
Keywords	Goodpasture syndrome ; lung failure ; ARDS ; ECMO-therapy ; eculizumab ; type IV collagen ; Medicine (General) ; R5-920
Subject code	610
Language	English
Publishing date	2021-09-01T00:00:00Z
Publisher	Frontiers Media S.A.
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Development and evaluation of the focused assessment of sonographic pathologies in the intensive care unit (FASP-ICU) protocol

Stefan Schmidt / Jana-Katharina Dieks / Michael Quintel / Onnen Moerer

Critical Care, Vol 25, Iss 1, Pp 1-

2021 Volume 12

Abstract: Abstract Background The use of ultrasonography in the intensive care unit (ICU) is steadily increasing but is usually restricted to examinations of single organs or organ systems. In this study, we combine the ultrasound approaches the most relevant to ... ...

Abstract	Abstract Background The use of ultrasonography in the intensive care unit (ICU) is steadily increasing but is usually restricted to examinations of single organs or organ systems. In this study, we combine the ultrasound approaches the most relevant to ICU to design a whole-body ultrasound (WBU) protocol. Recommendations and training schemes for WBU are sparse and lack conclusive evidence. Our aim was therefore to define the range and prevalence of abnormalities detectable by WBU to develop a simple and fast bedside examination protocol, and to evaluate the value of routine surveillance WBU in ICU patients. Methods A protocol for focused assessments of sonographic abnormalities of the ocular, vascular, pulmonary, cardiac and abdominal systems was developed to evaluate 99 predefined sonographic entities on the day of admission and on days 3, 6, 10 and 15 of the ICU admission. The study was a clinical prospective single-center trial in 111 consecutive patients admitted to the surgical ICUs of a tertiary university hospital. Results A total of 3003 abnormalities demonstrable by sonography were detected in 1275 individual scans of organ systems and 4395 individual single-organ examinations. The rate of previously undetected abnormalities ranged from 6.4 ± 4.2 on the day of admission to 2.9 ± 1.8 on day 15. Based on the sonographic findings, intensive care therapy was altered following 45.1% of examinations. Mean examination time was 18.7 ± 3.2 min, or 1.6 invested minutes per detected abnormality. Conclusions Performing the WBU protocol led to therapy changes in 45.1% of the time. Detected sonographic abnormalities showed a high rate of change in the course of the serial assessments, underlining the value of routine ultrasound examinations in the ICU. Trial registration The study was registered in the German Clinical Trials Register (DRKS, 7 April 2017; retrospectively registered) under the identifier DRKS00010428.
Keywords	Sonography ; Ultrasound ; General critical care ultrasound ; Whole-body ultrasound ; Critical care echocardiography ; Intensive care medicine ; Medical emergencies. Critical care. Intensive care. First aid ; RC86-88.9
Subject code	630
Language	English
Publishing date	2021-11-01T00:00:00Z
Publisher	BMC
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Critical Care Echocardiography as a Routine Procedure for the Detection and Early Treatment of Cardiac Pathologies

Stefan Schmidt / Jana-Katharina Dieks / Michael Quintel / Onnen Moerer

Diagnostics, Vol 10, Iss 671, p

2020 Volume 671

Abstract: Transthoracic and transesophageal echocardiography are important investigations in the intensive care unit (ICU) to diagnose acute cardiac pathologies and assess the haemodynamic status. Recommendations for critical care echocardiography (CCE) have been ... ...

Abstract	Transthoracic and transesophageal echocardiography are important investigations in the intensive care unit (ICU) to diagnose acute cardiac pathologies and assess the haemodynamic status. Recommendations for critical care echocardiography (CCE) have been published recently, but these still lack an evidence-based foundation. It is not known if performing transthoracic echocardiography (TTE) on a routine basis instead of only when required in acute cases is feasible or clinically useful. In this single-centre prospective observational study, we routinely performed TTE on 111 consecutive non-cardiological, non-cardiothoracic surgical ICU patients in two surgical ICUs in a tertiary care facility. Significant cardiac pathologies were detected in 82 (76.6%) and critical cardiac pathologies in 33 (30.8%) of the 107 patients. The most common critical cardiac pathologies were sPAP > 50 mmHg (19.63%), tricuspid annular plane systolic excursion ≤ 13 mm (9.4%), grade III diastolic dysfunction (8.4%), severe tricuspid valve insufficiency (5.6%) and left ventricular ejection fraction (LV-EF) ˂ 30% (4.7%). Some of the most commonly found cardiac pathologies are not well emphasised in current recommendations and training programs. We observed a progression of the cardiac pathologies previously described in 41 of the patients (91.1%). Patients with echocardiographic abnormalities had a significant survival disadvantage in the ICU. By performing CCE routinely, we observed the range and prevalence of cardiac pathologies that can be detected by echocardiography in critically ill patients. We recommend routine transthoracic CCE in ICU patients for early detection of cardiac pathologies and to help inform early intervention regimens, since cardiac conditions carry a significant survival disadvantage for the ICU patient.
Keywords	critical care echocardiography ; intensive care ; critical care ; transthoracic echocardiography ; cardiac disease ; transthoracic image quality ; Medicine (General) ; R5-920
Subject code	610
Language	English
Publishing date	2020-09-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Factor XIII Activity Might Already Be Impaired before Veno-Venous ECMO in ARDS Patients

Onnen Moerer / Jan Felix Huber-Petersen / Joern Schaeper / Claudia Binder / Saskia Wand

Journal of Clinical Medicine, Vol 10, Iss 1203, p

A Prospective, Observational Single-Center Cohort Study

2021 Volume 1203

Abstract: Direct complications in patients receiving extracorporeal (veno-venous) membrane oxygenation (vvECMO) are mainly either due to bleeding or thromboembolism. We aimed to evaluate the course of routine coagulation parameters and the activity of different ... ...

Abstract	Direct complications in patients receiving extracorporeal (veno-venous) membrane oxygenation (vvECMO) are mainly either due to bleeding or thromboembolism. We aimed to evaluate the course of routine coagulation parameters and the activity of different coagulation factors—with special focus on factor XIII (F XIII)—before, during and after vvECMO in acute respiratory distress syndrome (ARDS) patients. The activity of coagulation factors and rotational thrombelastometry were analyzed in 20 ECMO patients before (T-1) and 6 h (T0), one (T1), three (T3) and seven days (T7) after the implantation, as well as one and three days after the termination of ECMO. F XIII activity was already severely decreased to 37% (30/49) before ECMO. F XIII activity was the only coagulation factor continuously declining during vvECMO, being significantly decreased at T3 (31% (26/45) vs. 24% (18/42), p = 0.0079) and T7 (31% (26/45) vs. 23% (17/37), p = 0.0037) compared to T0. Three days after termination of vvECMO, platelet count and fibrinogen nearly doubled and factors II, V, XI and XIII showed spontaneous significant increases. Severe ARDS patients showed a considerably diminished factor XIII activity before vvECMO initiation and its activity continuously declined later on. Thus, incorporation of F XIII monitoring into the regular hemostaseologic routine during vvECMO therapy seems advisable. Due to the potential development of a hypercoagulatory state after the termination of vvECMO, tight hemostasiologic monitoring should persist in the initial phase after ECMO termination.
Keywords	extracorporeal membrane oxygenation ; ECMO ; ARDS ; coagulation ; factor XIII ; Medicine ; R
Subject code	610
Language	English
Publishing date	2021-03-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Biomarkers of Cholestasis and Liver Injury in the Early Phase of Acute Respiratory Distress Syndrome and Their Pathophysiological Value

Lars-Olav Harnisch / Sophie Baumann / Diana Mihaylov / Michael Kiehntopf / Michael Bauer / Onnen Moerer / Michael Quintel

Diagnostics, Vol 11, Iss 2356, p

2021 Volume 2356

Abstract: Background: Impaired liver function and cholestasis are frequent findings in critically ill patients and are associated with poor outcomes. We tested the hypothesis that hypoxic liver injury and hypoxic cholangiocyte injury are detectable very early in ... ...

Abstract	Background: Impaired liver function and cholestasis are frequent findings in critically ill patients and are associated with poor outcomes. We tested the hypothesis that hypoxic liver injury and hypoxic cholangiocyte injury are detectable very early in patients with ARDS, may depend on the severity of hypoxemia, and may be aggravated by the use of rescue therapies (high PEEP level and prone positioning) but could be attenuated by extracorporeal membrane oxygenation (ECMO). Methods: In 70 patients with ARDS, aspartate-aminotransferase (AST), alanin-aminotransferase (ALT) and gamma glutamyltransferase (GGT) were measured on the day of the diagnosis of ARDS and three more consecutive days (day 3, day 5, day 10), total bile acids were measured on day 0, 3, and 5. Results: AST levels increased on day 0 and remained constant until day 5, then dropped to normal on day 10 (day 0: 66.5 U/l; day 3: 60.5 U/l; day 5: 63.5 U/l, day 10: 32.1 U/l), ALT levels showed the exact opposite kinetic. GGT was already elevated on day 0 (91.5 U/l) and increased further throughout (day 3: 163.5 U/l, day 5: 213 U/l, day 10: 307 U/l), total bile acids levels increased significantly from day 0 to day 3 ( p = 0.019) and day 0 to day 5 ( p < 0.001), but not between day 3 and day 5 ( p = 0.217). Total bile acids levels were significantly correlated to GGT on day 0 ( p < 0.001), day 3 ( p = 0.02), and in a trend on day 5 ( p = 0.055). PEEP levels were significantly correlated with plasma levels of AST (day 3), ALT (day 5) and GGT (day 10). Biomarker levels were not associated with the use of ECMO, prone position, the cause of ARDS, and paO 2 . Conclusions: We found no evidence of hypoxic liver injury or hypoxic damage to cholangiocytes being caused by the severity of hypoxemia in ARDS patients during the very early phase of the disease. Additionally, mean PEEP level, prone positioning, and ECMO treatment did not have an impact in this regard. Nevertheless, GGT levels were elevated from day zero and rising, this increase was not related to ...
Keywords	ARDS ; cholestasis ; liver injury ; GGT ; bile acids ; Medicine (General) ; R5-920
Language	English
Publishing date	2021-12-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Longtime Neurologic Outcome of Extracorporeal Membrane Oxygenation and Non Extracorporeal Membrane Oxygenation Acute Respiratory Distress Syndrome Survivors

Lars-Olav Harnisch / Sebastian Riech / Marion Mueller / Vanessa Gramueller / Michael Quintel / Onnen Moerer

Journal of Clinical Medicine, Vol 8, Iss 7, p

2019 Volume 1020

Abstract: Neurologic complications following acute respiratory distress syndrome (ARDS) are well described, however, information on the neurologic outcome regarding peripheral nervous system complications in critically ill ARDS patients, especially those who ... ...

Abstract	Neurologic complications following acute respiratory distress syndrome (ARDS) are well described, however, information on the neurologic outcome regarding peripheral nervous system complications in critically ill ARDS patients, especially those who received extracorporeal membrane oxygenation (ECMO) are lacking. In this prospective observational study 28 ARDS patients who survived after ECMO or conventional nonECMO treatment were examined for neurological findings. Nine patients had findings related to cranial nerve innervation, which differed between ECMO and nonECMO patients ( p = 0.031). ECMO patients had severely increased patella tendon reflex (PTR) reflex levels ( p = 0.027 vs. p = 0.125) as well as gastrocnemius tendon reflex (GTR) ( p = 0.041 right, p = 0.149 left) were affected on the right, but not on the left side presumably associated with ECMO cannulation. Paresis (14.3% of patients) was only found in the ECMO group ( p = 0.067). Paresthesia was frequent (nonECMO 53.8%, ECMO 62.5%; p = 0.064), in nonECMO most frequently due to initial trauma and polyneuropathy, in the ECMO group mainly due to impairments of N. cutaneus femoris lateralis (4 vs. 0; p = 0.031). Besides well-known central neurologic complications, more subtle complications were detected by thorough clinical examination. These findings are sufficient to hamper activities of daily living and impair quality of life and psychological health and are presumably directly related to ECMO therapy.
Keywords	extracorporeal circulation ; ECMO ; acute respiratory distress syndrome (ARDS) ; Medicine ; R
Subject code	610
Language	English
Publishing date	2019-07-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Platelet Function Disturbance During Veno-Venous ECMO in ARDS Patients Assessed by Multiple Electrode Aggregometry—A Prospective, Observational Cohort Study

Saskia Wand / Jan Felix Huber-Petersen / Joern Schaeper / Claudia Binder / Onnen Moerer

Journal of Clinical Medicine, Vol 8, Iss 7, p

2019 Volume 1056

Abstract: Extracorporeal (veno-venous) membrane oxygenation (vvECMO) has been shown to have negative effects on platelet number and function. This study aimed to gain more information about the impact of vvECMO on platelet function assessed by multiple electrode ... ...

Abstract	Extracorporeal (veno-venous) membrane oxygenation (vvECMO) has been shown to have negative effects on platelet number and function. This study aimed to gain more information about the impact of vvECMO on platelet function assessed by multiple electrode aggregometry (MEA). Twenty patients with the indication for vvECMO were included. Platelet function was analyzed using MEA (Multiplate ® ) before (T-1), 6 h (T0), one (T1), two (T2), three (T3), and seven (T4) days after the beginning of vvECMO. Median aggregational measurements were already below the normal reference range before vvECMO initiation. Platelet aggregation was significantly reduced 6 h after vvECMO initiation compared to T-1 and spontaneously recovered with a significant increase at T2. Platelet count dropped significantly between T-1 and T0 and continuously decreased between T0 and T4. At T4, ADP-induced platelet aggregation showed an inverse correlation with the paO2 in the oxygenator. Platelet function should be assessed by MEA before the initiation of extracorporeal circulation. Although ECMO therapy led to a further decrease in platelet aggregation after 6 h, all measurements had recovered to baseline on day two. This implies that MEA as a whole blood method might not adequately reflect the changes in platelet function in the later stages of extracorporeal circulation.
Keywords	extracorporeal circulation ; ECMO ; multiplate ; platelet function ; multiple electrode aggregometry ; Medicine ; R
Subject code	630
Language	English
Publishing date	2019-07-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Activation of Sphingomyelinase-Ceramide-Pathway in COVID-19 Purposes Its Inhibition for Therapeutic Strategies

Murad Abusukhun / Martin S. Winkler / Stefan Pöhlmann / Onnen Moerer / Konrad Meissner / Björn Tampe / Heike Hofmann-Winkler / Michael Bauer / Markus H. Gräler / Ralf A. Claus

Frontiers in Immunology, Vol

2021 Volume 12

Abstract: Effective treatment strategies for severe coronavirus disease (COVID-19) remain scarce. Hydrolysis of membrane-embedded, inert sphingomyelin by stress responsive sphingomyelinases is a hallmark of adaptive responses and cellular repair. As demonstrated ... ...

Abstract	Effective treatment strategies for severe coronavirus disease (COVID-19) remain scarce. Hydrolysis of membrane-embedded, inert sphingomyelin by stress responsive sphingomyelinases is a hallmark of adaptive responses and cellular repair. As demonstrated in experimental and observational clinical studies, the transient and stress-triggered release of a sphingomyelinase, SMPD1, into circulation and subsequent ceramide generation provides a promising target for FDA-approved drugs. Here, we report the activation of sphingomyelinase-ceramide pathway in 23 intensive care patients with severe COVID-19. We observed an increase of circulating activity of sphingomyelinase with subsequent derangement of sphingolipids in serum lipoproteins and from red blood cells (RBC). Consistent with increased ceramide levels derived from the inert membrane constituent sphingomyelin, increased activity of acid sphingomyelinase (ASM) accurately distinguished the patient cohort undergoing intensive care from healthy controls. Positive correlational analyses with biomarkers of severe clinical phenotype support the concept of an essential pathophysiological role of ASM in the course of SARS-CoV-2 infection as well as of a promising role for functional inhibition with anti-inflammatory agents in SARS-CoV-2 infection as also proposed in independent observational studies. We conclude that large-sized multicenter, interventional trials are now needed to evaluate the potential benefit of functional inhibition of this sphingomyelinase in critically ill patients with COVID-19.
Keywords	molecular biology of critical care ; ceramide ; organ failure ; sphingomyelinase ; FIASMA ; drug repurposing ; Immunologic diseases. Allergy ; RC581-607
Subject code	610
Language	English
Publishing date	2021-12-01T00:00:00Z
Publisher	Frontiers Media S.A.
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