Abstract Objectives To survey physicians’ views on the risks and benefits of computed tomography (CT) in the management of septic patients and indications for and contraindications to contrast media use in searching for septic foci. Methods A web-based questionnaire was administered to physicians at a large European university medical center in January 2022. A total of 371 questionnaires met the inclusion criteria and were analyzed with physicians’ work experience, workplace, and medical specialty as independent variables. Chi-square tests were used for exploratory analysis. Results While physicians with all levels of work experience were included, the largest group (35.0%, n = 130/371) had 3–7 years of experience. Most physicians agreed that the benefits of CT outweigh its potential adverse effects in septic patients (90.5%, n = 336/371). Responders saw the strongest indication for contrast media administration in septic patients for (1) CT examinations of the abdomen (92.7%, n = 333/359) and (2) combined CT examinations of the chest, abdomen, and pelvis (94.1%, n = 337/358). While radiologists were most likely to consider manifest hyperthyroidism an absolute contraindication to contrast media administration (43.8%, n = 14/32), most other groups of physicians opted for appropriate preparation before contrast media administration in this subset of septic patients. Conclusion In this survey, most participating physicians considered CT an essential diagnostic modality to detect an infectious focus in septic patients. Whereas the risk of ionizing radiation was regarded as justifiable by most physicians, different specialties varied in their assessment of the risks of contrast media administration. Key Points Physicians recognize CT as a relevant imaging modality in the diagnostic management of patients with sepsis. There is an interdisciplinary consensus that the use of ionizing radiation is justified in septic patients. There is disagreement about indications for and contraindications to contrast media administration among physicians from different medical specialties. Graphical Abstract

Critical illness often leads to the development of intestinal dysbiosis, which can have a significant impact on disease outcome. Intestinal barrier dysfunction is a common problem in intensive care unit patients, particularly those with sepsis. Despite its importance, early and reliable diagnosis of barrier dysfunction and evaluation of therapeutic options remain lacking in clinical practice. Given that intestinal hyperpermeability is associated with increased translocation of luminal antigens and subsequent priming of naïve T cells, we hypothesized that analysis of circulating peripheral antigen-reactive T cells could provide insight into the functionality of the intestinal barrier. To test this hypothesis, 70 ICU patients were enrolled, including those with sepsis, those not meeting sepsis criteria, and COVID-19 patients, as well as 20 healthy volunteers. We identified a sepsis-specific T-helper cell signature in peripheral blood using the antigen-reactive T-cell enrichment (ARTE) technique followed by flow cytometric analysis. This signature was characterized by an expansion of gut trophic Bifidobacterium longum-reactive T-helper cells, indicating significant intestinal barrier dysfunction during sepsis. This approach allows the study of intestinal barrier functionality and provides a means to monitor the effects of potential therapeutic interventions over time using blood samples.

This study aims to describe physicians’ perspectives on the use of computed tomography (CT) in patients with sepsis. In January 2022, physicians of a large European university medical center were surveyed using a web-based questionnaire asking about their views on the role of CT in sepsis. A total of 371 questionnaires met the inclusion criteria and were analyzed using work experience, workplace, and medical specialty of physicians as variables. Chi-square tests were performed. Physicians considered the ability to detect an unknown focus as the greatest benefit of CT scans in sepsis (70.9

Background: Malnutrition as well as overfeeding can have negative impacts on clinical outcomes in critically ill patients. Continuous veno-venous hemodialysis (CVVHD) with regional citrate anticoagulation (RCA) using trisodium citrate 4% (TSC) might play a role in nutrient disposition in patients in the ICU. Methods: In 33 consecutive patients on CVVHD with RCA, energy uptake or loss was calculated. Three macronutrients (lactate, glucose and citrate) were analyzed by taking prefilter blood and effluent samples. Results: Glucose and lactate clearance through CVVHD made up for a loss of 61 kcal/d (IQR 25–164 kcal/d) and 38 kcal/d (IQR 23–59 kcal/d), respectively. Two patients with hyperglycemic state (>350 mg/dL) lost around 600 kcal/d during CVVHD. Net post-filter citrate caloric delivery through RCA was 135 kcal/d (IQR: 124–144 kcal/d). Adding the three macronutrients, net caloric gain through CVVHD was 10 kcal/d (IQR: −63–75 kcal/d). Conclusion: In non-hyperglycemic patients on CVVHD with RCA, the metabolic contribution of the three macronutrients lactate, glucose and citrate is neglectable.

Hypo- und Hypernatriämien sind bei intensivmedizinischen Patienten sehr häufig und stehen in engem Zusammenhang mit Volumenstörungen und dem Volumenmanagement auf der Intensivstation. Sie sind mit einer längeren intensivstationären Verweildauer und einer deutlich erhöhten Mortalität assoziiert und ihre Behandlung ist komplexer, als es auf den ersten Blick scheint. Hyponatriämien werden anhand von Tonizität und Volumenstatus differenziert. Bei hypertonen und isotonen Hyponatriämien steht die Therapie der zugrunde liegenden Hyperglykämie im Vordergrund. Bei hypotonen hypovolämischen Hyponatriämien erfolgt eine Therapie mit balancierten kristalloiden Lösungen, bei schweren eu-/hypervolämischen hypotonen Hyponatriämien eine Akuttherapie mit hypertoner Kochsalzlösung. Hypervolämische Hypernatriämien treten fast ausschließlich bei intensivstationären Patienten auf und sind oft durch die Infusion hypertoner Lösungen bedingt. Es gibt wenig Evidenz für die Therapie, wobei hypotone Infusionen in Verbindung mit einer diuretischen Therapie ein Ansatz sein können. Es sollte großes Augenmerk auf die Prävention gelegt werden und die Infusion hypertoner Lösungen vermieden werden. Störungen der Plasmanatriumkonzentration sind häufig, bedürfen großer Aufmerksamkeit und es sollte eine sorgfältige diagnostische Einteilung erfolgen sowie die Volumentherapie entsprechend ausgerichtet werden.

While invasive thermodilution techniques remain the reference methods for cardiac output (CO) measurement, there is a currently unmet need for non-invasive techniques to simplify CO determination, reduce complications related to invasive procedures required for indicator dilution CO measurement, and expand the application field toward emergency room, non-intensive care, or outpatient settings. We evaluated the performance of a non-invasive oscillometry-based CO estimation method compared to transpulmonary thermodilution. To assess agreement between the devices, we used Bland–Altman analysis. Four-quadrant plot analysis was used to visualize the ability of Mobil-O-Graph (MG) to track CO changes after a fluid challenge. Trending analysis of CO trajectories was used to compare MG and PiCCO ® calibrated pulse wave analysis over time (6 h). We included 40 patients from the medical intensive care unit at the Charité – Universitätsmedizin Berlin, Campus Benjamin Franklin between November 2019 and June 2020. The median age was 73 years. Forty percent of the study population was male; 98% was ventilator-dependent and 75% vasopressor-dependent at study entry. The mean of the observed differences for the cardiac output index (COI) was 0.7 l ∗ min –1* m –2 and the lower, and upper 95% limits of agreement (LOA) were -1.9 and 3.3 l ∗ min –1* m –2 , respectively. The 95% confidence interval for the LOA was ± 0.26 l ∗ min –1* m –2 , the percentage error 83.6%. We observed concordant changes in CO with MG and PiCCO ® in 50% of the measurements after a fluid challenge and over the course of 6 h. Cardiac output calculation with a novel oscillometry-based pulse wave analysis method is feasible and replicable in critically ill patients. However, we did not find clinically applicable agreement between MG and thermodilution or calibrated pulse wave analysis, respectively, assessed with established evaluation routine using the Bland–Altman approach and with trending analysis methods. In summary, we do not recommend the use of this method in critically ill patients at this time. As the basic approach is promising and the CO determination with MG very simple to perform, further studies should be undertaken both in hemodynamically stable patients, and in the critical care setting to allow additional adjustments of the underlying algorithm for CO estimation with MG.

BACKGROUNDArginine-vasopressin (AVP) binding to vasopressin V2 receptors promotes redistribution of the water channel aquaporin-2 (AQP2) from intracellular vesicles into the plasma membrane of renal collecting duct principal cells. This pathway fine-tunes renal water reabsorption and urinary concentration, and its perturbation is associated with diabetes insipidus. Previously, we identified the antimycotic drug fluconazole as a potential modulator of AQP2 localization.METHODSWe assessed the influence of fluconazole on AQP2 localization in vitro and in vivo as well as the drug's effects on AQP2 phosphorylation and RhoA (a small GTPase, which under resting conditions, maintains F-actin to block AQP2-bearing vesicles from reaching the plasma membrane). We also tested fluconazole's effects on water flow across epithelia of isolated mouse collecting ducts and on urine output in mice treated with tolvaptan, a VR2 blocker that causes a nephrogenic diabetes insipidus-like excessive loss of hypotonic urine.RESULTSFluconazole increased plasma membrane localization of AQP2 in principal cells independent of AVP. It also led to an increased AQP2 abundance associated with alterations in phosphorylation status and ubiquitination as well as inhibition of RhoA. In isolated mouse collecting ducts, fluconazole increased transepithelial water reabsorption. In mice, fluconazole increased collecting duct AQP2 plasma membrane localization and reduced urinary output. Fluconazole also reduced urinary output in tolvaptan-treated mice.CONCLUSIONSFluconazole promotes collecting duct AQP2 plasma membrane localization in the absence of AVP. Therefore, it might have utility in treating forms of diabetes insipidus (e.g., X-linked nephrogenic diabetes insipidus) in which the kidney responds inappropriately to AVP.

Innerklinische Reanimationen werden von speziellen Reanimationsteams durchgeführt, die Versorgung anderer Notfälle ist in deutschen Kliniken weniger stringent organisiert. Rapid-Response-Systeme mit definierten Alarmierungskriterien sind bislang kaum etabliert, Daten zur innerklinischen Notfallversorgung nur in geringem Umfang vorhanden.

Assessment of the cardiac output (CO) is usually performed with invasive techniques requiring specialized equipment in the intensive care unit (ICU). With TEL-O-GRAPH (TG), CO can be derived from the oscillometrically obtained brachial pulse wave during the measurement of brachial blood pressure. CO and stroke volume (SV) determinations with TG were compared with transpulmonary thermodilution measurements with the PICCO system (PICCO) in 38 haemodynamically unstable ICU patients with a total of 84 comparison measurements performed. SV (33.3 ± 9.0 ml/m2 vs. 44.3 ± 14.4 ml/m2, p < 0.001) and CO (2.7 ± 0.5 l/min/m2 vs. 3.8 ± 1.2 l/min/m2, p < 0.001) were underestimated significantly with TG and oscillometric brachial systolic blood pressure (BP) was significantly lower and diastolic BP significantly higher than invasive femoral artery pressure. A linear correlation was found between CO dimension and CO underestimation with TG. Correct tracking of CO changes with a fluid challenge was possible in 69.5% of measurements. Oscillometric noninvasive CO is possible in the ICU, but accuracy and precision of this new method are lacking. Implementation of a correction factor accounting for the linear increase in CO underestimation observed with increasing CO could improve CO assessment with TG in haemodynamically unstable patients.

BACKGROUND Insulin-delivery algorithms for achieving glycemic control in the intensive care unit require frequent checks of blood glucose level and thus increase nursing workload. Hypoglycemia is a serious complication associated with intensive insulin therapy.OBJECTIVES To evaluate a nurse-directed protocol for blood glucose management that allows individualized insulin delivery within a predefined blood glucose corridor, intended to avoid hypoglycemia while maintaining adequate control of blood glucose level without increasing nursing workload.METHODS A nurse-directed protocol for blood glucose management was developed by an interprofessional team, and the protocol's performance was investigated in 175 patients compared with 384 historical controls.RESULTS With the nurse-directed protocol, hypoglycemia incidents declined significantly (31% vs 12%, P < .001), and minimum blood glucose levels increased significantly (80 mg/dL vs 93 mg/dL, P < .001). Mean and maximum blood glucose levels, the proportion of glucose readings within the target range (31% vs 26%, P = .06), and the number of blood glucose checks (59 vs 58, P = .85) remained unchanged with use of the protocol.CONCLUSION Implementation of the nurse-directed protocol for blood glucose management did not increase nursing workload but reduced hypoglycemia incidents significantly while maintaining adequate glycemic control.

Objective: To assess feasibility and accuracy of oscillometric cardiac output (CO) calculation. Design and method: A prospective comparison of oscillometric CO determinations and reference themodilution CO measurements was performed in 38 intensive care unit patients (June 2015 to June 2016). Thermodilution CO was obtained using transpulmonary technique (PiCCO®, Pulsion Medical Systems, Feldkirchen, Germany), and oscillometric CO was calculated using the Tel-O-GRAPH® (TG) non-invasive blood pressure measurement and hemodynamic assessment device (IEM, Stolberg, Germany). CO was indexed to body surface area and is referred to as cardiac index (CI). Bland Altman analysis was employed to assess differences between oscillometric and reference CI as well as non-invasive (TG) and invasive (PiCCO®) blood pressure (BP) measurements. Results: Two-thirds of the study population was male (68.4%), mean age was 68 years. Almost all patients were mechanically ventilated (95%) at study entry, and vasopressor therapy was required in 76%. Oscillometric CI determination yielded significantly lower results than the reference method (3.8 ± 1.22 l/min*m2 vs. 2.73 ± 0.50 l/min*m2, p < 0.0001) with a bias of 1.08 l/min*m2 and limits of agreement of ± 2.23 l/min*m2 (percentage error 62%). With TG, both measured brachial (117.5 ± 16.0 mmHg) and estimated aortic (107.2 ± 15.6) systolic BP were significantly lower than invasive PiCCO® femoral BP (123.6 ± 17.4 mmHg, p = 0.005 and p < 0.0001) with a bias of 5.9 mmHg and 16.1 mmHg, respectively, and limits of agreement of ± 23.46 mmHg and ± 23.79 mmHg.Conclusions: TG significantly underestimates CO in hemodynamically unstable patients. This finding could in part be explained by the significantly lower BP readings obtained with TG. In addition, Bland-Altman analysis revealed a linear relationship between CO values and divergence of TG CO from reference measurement (figure). A correction factor could potentially alleviate CO underestimation with TG, and thus make this noninvasive easy method of CO determination more reliable

BACKGROUND: Transpulmonary thermodilution (TPTD) is used frequently in the intensive care unit to determine cardiac index (CI), intrathoracic blood volume index (ITBVI), and extravascular lung volume index (EVLWI). Renal replacement therapy (RRT) influences TPTD results, but the underlying mechanisms are not completely understood. We hypothesized that RRT blood flow induces errors in TPTD measurements. METHODS: We analyzed TPTD data available from the PiCCO® plus hemodynamic measurement device on a personal computer using a proprietary Pulsion Medical Systems software. By using the dialysis catheter to inject the thermal indicator, 20 measurement series were performed in 12 intensive care unit patients determining CI, ITBVI, and EVLWI during RRT with the blood pump stopped, and at flows of 100 and 200 mL/min, respectively. RESULTS: Data export was successful in 17 measurement series and showed a significant decrease in measured CI (6.5 ± 2.5 vs 5.4 ± 1.9 L/min/m 2 , P < 0.001) and ITBVI (1358.8 ± 274.5 vs 1132.8 ± 218.3 mL/m 2 , P < 0.001) with RRT and a significant increase in EVLWI (8.6 ± 4.4, 10.2 ± 4.5 mL/kg, P < 0.001). Blood temperature before and the temperature decrease after injection of the thermal indicator were unchanged by RRT. Mean transit time and downslope time of the thermodilution curve, however, were both increased with the RRT blood pump running ( P ≤ 0.001). CONCLUSIONS: Analysis of TPTD data shows that thermodilution curve forms are modified with RRT, resulting in an erroneous calculation of thermodilution-derived hemodynamic parameters.

Management of volume status is difficult in critically ill patients with renal failure. Volumetric hemodynamic indices are increasingly being used to guide fluid therapy in the intensive care unit (ICU), but are not established to monitor hemodialysis-induced fluid removal in critically ill patients. Using volumetric hemodynamic monitoring, changes in extravascular lung water index (EVLWI) and intrathoracic blood volume index (ITBVI) were measured immediately before and after hemodialysis sessions in 35 ICU patients. Additional hemodynamic and oxygenation related parameters were recorded at the same time, and online relative blood volume (RBV) monitoring was performed during hemodialysis. EVLWI decreased significantly with fluid removal (median 10.0 vs. 9.6mL/kg, P=0.001), whereas ITBVI remained stable (median 1012 vs. 1029mL/m(2), P=0.402). Significant changes were also observed in stroke volume variation (median 12.0 vs. 13.0 %, P=0.012), cardiac index (median 4.2 vs. 3.5mL/min/m(2), P=0.003), mean arterial pressure (median 77 vs. 85.5mmHg, P=0.006), norepinephrine dose (median 0.092 vs. 0.114g/kg per min, P=0.043), and hemoglobin values (median 9.5 vs. 10.4gm/dL, P=0.036). RBV decreased by 7.8% (median); there was no correlation with either the volumetric measurements or the other hemodynamic parameters recorded. EVLWI reduction with dialysis reflects the removal of excess body fluid, whereas preservation of cardiac preload is indicated by ITBVI stability. Volumetric hemodynamic measurements provide additional information concerning fluid status and are thus potentially useful to guide fluid removal on hemodialysis in critically ill patients.

BACKGROUND Early enteral nutrition is recommended for patients in intensive care units, but nutrition provision is often hindered by a variety of unit-specific problems. OBJECTIVES To evaluate the impact of a nutrition support protocol on nutrition prescription and delivery in the intensive care unit. METHODS Nutrition-related data from 73 patients receiving mechanical ventilation who were treated in an adult medical intensive care unit before introduction of an enteral nutrition support protocol were retrospectively compared with data for 87 patients admitted after implementation of the protocol. RESULTS After implementation of the protocol, enteral nutrition was started significantly earlier (P = .007) and enteral feeding goals were reached significantly faster (6 vs 10 days, P < .001) than before. Prescription of enteral nutrition on the first day of invasive mechanical ventilation increased from 38% before to 54% after (P = .03) implementation of the protocol. Prescribed and delivered nutrition doses on the first 2 days of mechanical ventilation also increased significantly (P < .001) after the protocol was implemented. Nasojejunal feeding tubes were used in 52% of patients before and 56% of patients after protocol implementation P = .63). Jejunal tubes were placed earlier after the protocol was implemented than before (median 5 vs 6.5 days), and when a jejunal tube was in place, feeding goals were reached faster (median 2 vs 3 days, P = .002). CONCLUSION Implementing an enteral nutrition support protocol shortened the time to reach feeding goals. Jejunal feeding tubes were necessary in more than half of the patients, and with a jejunal feeding tube in place, feeding goals were reached rapidly.

The introduction of automated oscillometric blood pressure monitors was the basis for today’s widespread use of blood pressure self-measurement. However, in atrial fibrillation, there is a controversial debate on the use of oscillometry because there is a high variability of heart rate and stroke volume. To date, the accuracy of oscillometric blood pressure monitoring in atrial fibrillation has only been investigated using auscultatory sphygmomanometry as reference method, which may be biased by arrhythmia as well. We performed a cross-sectional study in 102 patients (52 sinus rhythm, 50 atrial fibrillation) assessing the accuracy of an automated and validated oscillometric upper arm (M5 Professional, Omron) and wrist device (R5 Professional, Omron) to invasively assessed arterial pressure. Blood pressure values were calculated as the mean of 3 consecutive measurements. Systolic and diastolic blood pressure did not significantly differ in patients with sinus rhythm and atrial fibrillation, independent of the method of measurement ( P >0.05 each). The within-subject variability of the oscillometric measurements was higher in patients with atrial fibrillation compared with sinus rhythm ( P <0.01 each). The biases of systolic and diastolic blood pressure, however, did not significantly differ in presence or absence of atrial fibrillation in Bland-Altmann analysis ( P >0.05 each). In conclusion, atrial fibrillation did not significantly affect the accuracy of oscillometric measurements, if 3 repeated measurements were performed.