Frederik Trinkmann

Diagnostic and prognostic utility of soluble CD 14 subtype (presepsin) for severe sepsis and septic shock during the first week of intensive care treatment

IntroductionThe aim of this study was to evaluate the diagnostic and prognostic value of presepsin in patients with severe sepsis and septic shock during the first week of ICU treatment.MethodsIn total, 116 patients with suspected severe sepsis or septic shock were included during the first 24 hours of ICU treatment. Blood samples for biomarker measurements of presepsin, procalcitonin (PCT), interleukin 6 (IL-6), C reactive protein (CRP) and white blood cells (WBC) were drawn at days 1, 3 and 8. All patients were followed up for six months. Biomarkers were tested for diagnosis of sepsis, severe sepsis, septic shock and for prognosis of 30-days and 6-months all-cause mortality at days 1, 3 and 8. Diagnostic and prognostic utilities were tested by determining diagnostic cutoff levels, goodness criteria, C-statistics and multivariable Cox regression models.ResultsPresepsin increased significantly from the lowest to most severe sepsis groups at days 1, 3 and 8 (test for linear trend P <0.03). Presepsin levels revealed valuable diagnostic capacity to diagnose severe sepsis and septic shock at days 1, 3 and 8 (range of diagnostic area under the curves (AUC) 0.72 to 0.84, P = 0.0001) compared to IL-6, PCT, CRP and WBC. Goodness criteria for diagnosis of sepsis severity were analyzed (≥sepsis, cutoff = 530 pg/ml; ≥severe sepsis, cutoff = 600 pg/ml; ≥septic shock, cutoff = 700 pg/ml; P <0.03). Presepsin levels revealed significant prognostic value for 30 days and 6 months all-cause mortality (presepsin: range of AUC 0.64 to 0.71, P <0.02). Patients with presepsin levels of the 4th quartile were 5 to 7 times more likely to die after six months than patients with lower levels. The prognostic value for all-cause mortality of presepsin was comparable to that of IL-6 and better than that of PCT, CRP or WBC.ConclusionsIn patients with suspected severe sepsis and septic shock, presepsin reveals valuable diagnostic capacity to differentiate sepsis severity compared to PCT, IL-6, CRP, WBC. Additionally, presepsin and IL-6 reveal prognostic value with respect to 30 days and 6 months all-cause mortality throughout the first week of ICU treatment.Trial registrationClinicalTrials.gov NCT01535534. Registered 14 February 2012.

Noninvasive determination of cardiac output by the inert-gas-rebreathing method--comparison with cardiovascular magnetic resonance imaging.

Background: An easy, noninvasive and accurate technique for measuring cardiac output (CO) would be desirable for the diagnosis and therapy of cardiac diseases. Innocor, a novel inert-gas-rebreathing (IGR) system, has shown promising results in smaller studies. An extensive evaluation in a larger, less homogeneous patient collective is lacking. Methods: We prospectively assessed the accuracy and reproducibility of CO measurements obtained by IGR in 305 consecutive patients as compared to the noninvasive gold standard, cardiovascular magnetic resonance (CMR) imaging. Results: Bland-Altman analysis showed a good correspondence of the two methods for CO measurement with an average deviation of 0.2 ± 1.0 liters/min (mean ± SD) and a good reproducibility with a mean bias of 0.2 ± 0.5 liters/min. The accuracy of the present measurements at rest was significantly better in the physiological range than in higher or lower CO ranges. The error levels set forth by current recommendations were exceeded. Conclusion: The data show that IGR measurements are easy to perform and show good agreement with CMR; however, the technique appears to be less accurate in extreme CO ranges at rest. The clinical importance of the IGR method remains to be proven by further studies.

A Novel Noninvasive Ultrasonic Cardiac Output Monitor: Comparison With Cardiac Magnetic Resonance

USCOM, a novel continuous wave Doppler (CWD) device, has been introduced for noninvasive determination of cardiac output (CO). The present study aimed to compare the accuracy and reproducibility of the new device, using cardiovascular magnetic resonance imaging (CMR) as the noninvasive gold standard.

Is Arterial Pulse Contour Analysis Using Nexfin a New Option in the Noninvasive Measurement of Cardiac Output?—A Pilot Study

OBJECTIVES A growing interest in monitoring cardiac output (CO) noninvasively has emerged; however, its determination has been difficult using the standard approaches. The aim of this study was to evaluate the accuracy and precision of pulse contour analysis (PCA) compared with cardiac magnetic resonance imaging (CMR). DESIGN A single-center prospective study. SETTING A university hospital. PARTICIPANTS Thirty-nine consecutive stable patients undergoing CMR. INTERVENTIONS CO was determined twice by PCA using the Nexfin monitoring system (BMEYE BV, Amsterdam, The Netherlands). Measurements were performed after 10 minutes of rest in a stable supine position immediately before or after the CMR examination. MEASUREMENTS AND MAIN RESULTS There was a mean bias of 0.2 ± 1.9 L/min between CMR and PCA and a reproducibility of 0.2 ± 0.6 L/min for PCA. Between 4.8 and 6.3 L/min (second quartile of COCMR), there was a good agreement (mean bias = -0.2 ± 1.3 L/min). Comparing quartile 1 (-1.3 ± 2.0 L/min) overestimating and quartiles 3 (1.4 ± 0.9 L/min) and 4 (0.9 ± 2.0 L/min) underestimating CO, a statistically significant difference was found. The reproducibility was not affected by the quartile (p = 0.23, analysis of variance), whereas there was a significant difference between the nonoutlier and outlier group when using the Mann-Whitney U test (p = 0.02). CONCLUSIONS Noninvasive PCA allows the safe and economic measurement of CO, yet it still has major limitations. Although the agreement with CMR was acceptable, there was a clinically unacceptable variation; absolute values should not be used interchangeably. These results suggest that therapeutic interventions and clinical decisions should not be based on noninvasive PCA measurements at the present time.

Non-invasive determination of cardiac output: Comparison of a novel CW Doppler ultrasonic technique and inert gas rebreathing

BACKGROUND Cardiac Output (CO) is an important parameter in the diagnosis and therapy of heart diseases. Inert gas rebreathing (IGR) and continuous wave Doppler ultrasound (CWD) are among the most promising newer techniques aiming at a non-invasive, point of care measurement of CO. A direct comparison of the two methods has not yet been carried out. METHODS 63 consecutive patients were included in the study. CO was measured twice with both CWD and IGR to assess inter-method agreement and reproducibility. The statistical comparisons were performed as proposed by Bland and Altman. RESULTS There was a significant correlation between the CO measurements by both methods (r=0.53, p<0.001). Bland-Altman analysis showed a good agreement of measurements with a bias of 0.4+/-1.0 l/min (mean+/-standard deviation). Both methods showed a good reproducibility. CWD measurements were not possible in 14% of patients while IGR measurements were not possible in 5% of patients (p=0.13). CONCLUSION The determination of CO by IGR and CWD revealed a good agreement and reproducibility with a low rate of impossible measurements, suggesting that IGR and CWD can be used interchangeably in the clinical setting.

Non-Invasive Measurement of Cardiac Output during Atrial Fibrillation: Comparison between Cardiac Magnetic Resonance Imaging and Inert Gas Rebreathing

Objectives: Atrial fibrillation (AF) is one of the most frequent heart rhythm disorders. It potentially influences cardiac function and its measurement. Cardiac magnetic resonance imaging (CMR) has become the new gold standard for non-invasive assessment of cardiac output (CO). A novel inert gas rebreathing (IGR) device based on the Fick Principle also proved promising in patients in sinus rhythm (SR). The aim of our study was to compare the agreement of non-invasive CO measurements between CMR and IGR in AF patients. Methods: A total of 68 patients, 34 with AF and 34 pair-matched controls in SR, were included. Results: Bland-Altman analysis showed good agreement between both methods, with an average deviation of 0.2 ±1.2 l/min in the AF group versus 0.3 ±1.0 l/min in the SR group (p = 0.77). IGR demonstrated good agreement for CO between 2.0 and 5.4 l/min. However, in hyperdynamic circulatory conditions (CO >5.5 l/min), the increasing disagreement of IGR and CMR measurements reached statistical significance. Conclusions: Non-invasive CO measurements using CMR and IGR are feasible in patients suffering from AF. Good agreement was found between the two methods in an unselected cohort. Hyperdynamic circulatory conditions can lead to significant measurement differences which, however, do not affect the reproducibility of IGR.

Inert gas rebreathing: the effect of haemoglobin based pulmonary shunt flow correction on the accuracy of cardiac output measurements in clinical practice.

Background:  Cardiac output (CO) is an important cardiac parameter, however its determination is difficult in clinical routine. Non‐invasive inert gas rebreathing (IGR) measurements yielded promising results in recent studies. It directly measures pulmonary blood flow (PBF) which equals CO in absence of significant pulmonary shunt flow (QS). A reliable shunt correction requiring the haemoglobin concentration (cHb) as only value to be entered manually has been implemented. Therefore, the aim of the study was to evaluate the effect of various approaches to QS correction on the accuracy of IGR.

Ezetimibe inhibits platelet activation and uPAR expression on endothelial cells

PURPOSE Lipid lowering therapy constitutes the basis of cardiovascular disease therapy. The purpose of this study was to investigate effects of ezetimibe, a selective inhibitor of intestinal cholesterol absorption, on platelets and endothelial cells in an in vitro endothelial cell model. METHODS After a 24h incubation period with ezetimibe (concentrations 1, 50, 100 and 1000ng/ml), human umbilical vein endothelial cells (HUVEC) were stimulated for 1h with lipopolysaccharide (LPS) and were then incubated in direct contact with activated platelets. Following this, the expression of CD40L and CD62P on platelets, and the expression of ICAM-1, VCAM-1, uPAR, and MT1-MMP on endothelial cells were measured by flow cytometry. Supernatants were analysed by enzyme linked immunosorbent assay for soluble MCP-1, IL-6 and MMP-1. RESULTS The increased expression of uPAR on endothelial cells by proinflammatory stimulation with LPS and by direct endothelial contact with activated platelets was significantly reduced through pre-incubation with 100ng/ml and 1000ng/ml ezetimibe (p<0.05). Platelets directly incubated with ezetimibe but without endothelial cell contact showed significantly reduced CD62P and CD40L surface expression (p<0.05). Ezetimibe had no significant effects on HUVEC expression of MT1-MMP, ICAM-1 and VCAM-1 and on CD40L expression on platelets in direct contact with endothelial cells. Levels of soluble IL-6 in HUVEC supernatants were significantly lower after pre-incubation with ezetimibe. CONCLUSION In this in vitro analysis, ezetimibe directly attenuates platelet activation and has significant endothelial cell mediated effects on selected markers of atherosclerosis.

Multiple coupled resonances in the human vascular tree: refining the Westerhof model of the arterial system

The human arterial vascular tree can be described by multicompartment models using electrical components. First introduced in the 1960s by Noordergraaf and Westerhof, these hardware-based approaches required several simplifications. We were able to remove the restrictions using modern software simulation tools and improve overall model quality considerably. Whereas the original Westerhof model consisted of 121 Windkessel elements, the refined model has 711 elements and gives realistic pulse waveforms of the aorta and brachial and radial arteries with realistic blood pressures. Moreover, novel insights concerning the formation of the physiological aortic-to-radial transfer function were gained. Its being potentially due to the coupling of many small resonant elements gives new impetus to the discussion of arterial pressure wave reflection. The individualized transfer function derived from our improved model incorporates distinct patient characteristics and can potentially be used for estimation of central blood pressure values. NEW & NOTEWORTHY We were able to find an individualized transfer function giving realistic pulse waveforms and blood pressures using a multicompartment model of the arterial system. Based on the hardware-built Westerhof approach, several simplifications initially introduced in the 1960s could be reversed using software simulation. Overall model quality was improved considerably, and multiple coupled resonances were identified as potential explanation for the formation of the aortic-to-radial transfer function, giving new impetus to the discussion of arterial pressure wave reflection.

Finding the right spot: Where to measure airway parameters in patients with COPD

PURPOSE The importance of spirometry for management of COPD was reduced in the 2017 revision of the GOLD report. CT derived airway measurements show strong correlations with lung function tests and symptoms. However, these correlations are specific to the airway localization, and currently there is no evidence for the ideal spot. Therefore, the aim of this prospective study was to systematically correlate CT derived airway measurements with extensive lung function testing. METHODS AND MATERIALS 65 patients with diagnosed COPD underwent body plethysmography, impulse oscillometry and dose optimized qCT examination (Somatom Force, Healthineers, Germany) in inspiration and expiration. Eight airway parameters (e.g. outer diameter, maximal wall thickness) were acquired for both scans in every lobe for the third to fifth generation bronchus and correlated with the lung function tests. RESULTS The most significant correlations between airway parameters were found for the third generation bronchus of the upper left lobe during expiration (25 out of 48 correlation pairs, mean r = -0.39) and for the third generation bronchus of the upper right lobe during inspiration (9 out of 48 correlation pairs, mean r = -0.25). No significant correlations were for example found for the upper right lobe in expiration. CONCLUSION Correlations between airway parameters and lung function tests vary widely between lobes, bronchus generations and breathing states. Our work suggests that the third generation bronchus of the upper left lobe in expiration could be the preferred localization for airway quantification in future studies.