Applicability of stroke volume variation in patients of a general intensive care unit: a longitudinal observational study.

Sinus rhythm (SR) and controlled mechanical ventilation (CV) are mandatory for the applicability of respiratory changes of the arterial curve such as stroke volume variation (SVV) to predict fluid-responsiveness. Furthermore, several secondary limitations including tidal volumes <8 mL/kg and SVV-values within the "gray zone" of 9-13% impair prediction of fluid-responsiveness by SVV. Therefore, we investigated the prevalence of these four conditions in general ICU-patients. This longitudinal observational study analyzed a prospectively maintained haemodynamic database including 4801 transpulmonary thermodilution and pulse contour analysis measurements of 278 patients (APACHE-II 21.0 ± 7.4). The main underlying diseases were cirrhosis (32%), sepsis (28%), and ARDS (17%). The prevalence of SR and CV was only 19.4% (54/278) in the first measurements (primary endpoint), 18.8% (902/4801) in all measurements and 26.5% (9/34) in measurements with MAP < 65 mmHg and CI < 2.5 L/min/m2 and vasopressor therapy. In 69.1% (192/278) of the first measurements and in 65.9% (3165/4801) of all measurements the patients had SR but did not have CV. In 1.8% (5/278) of the first measurements and in 2.5% (119/4801) of all measurements the patients had CV but lacked SR. In 9.7% (27/278) of the first measurements and in 12.8% (615/4801) of all measurements the patients did neither have SR nor CV. Only 20 of 278 (7.2%) of the first measurements and 8.2% of all measurements fulfilled both major criteria (CV, SR) and both minor criteria for the applicability of SVV. The applicability of SVV in ICU-patients is limited due to the absence of mandatory criteria during the majority of measurements.

Femoral indicator injection for transpulmonary thermodilution using the EV1000/VolumeView(®): do the same criteria apply as for the PiCCO(®)?

OBJECTIVE: Comparison of global end-diastolic volume index (GEDVI) obtained by femoral and jugular transpulmonary thermodilution (TPTD) indicator injections using the EV1000/VolumnView(®) device (Edwards Lifesciences, Irvine, USA). METHODS: In an 87-year-old woman with hypovolemic shock and equipped with both jugular and femoral vein access and monitored with the EV1000/VolumeView(®) device, we recorded 10 datasets, each comprising duplicate TPTD via femoral access and duplicate TPTD (20 ml cold saline) via jugular access. RESULTS: Mean femoral GEDVI ((674.6±52.3) ml/m(2)) was significantly higher than jugular GEDVI ((552.3±69.7) ml/m(2)), with P=0.003. Bland-Altman analysis demonstrated a bias of (+122±61) ml/m(2), limits of agreement of -16 and +260 ml/m(2), and a percentage error of 22%. Use of the correction-formula recently suggested for the PiCCO(®) device significantly reduced bias and percentage error. Similarly, mean values of parameters derived from GEDVI such as pulmonary vascular permeability index (PVPI; 1.244±0.101 vs. 1.522±0.139; P<0.001) and global ejection fraction (GEF; (24.7±1.6)% vs. (28.1±1.8)%; P<0.001) were significantly different in the case of femoral compared to jugular indicator injection. Furthermore, the mean cardiac index derived from femoral indicator injection ((4.50±0.36) L/(min·m²)) was significantly higher (P=0.02) than that derived from jugular indicator injection ((4.12±0.44) L/(min·m²)), resulting in a bias of (+0.38±0.37) L/(min·m²) and a percentage error of 19.4%. CONCLUSIONS: Femoral access for indicator injection results in markedly altered values provided by the EV1000/VolumeView(®), particularly for GEDVI, PVPI, and GEF.

Transpulmonary thermodilution (TPTD) before, during and after Sustained Low Efficiency Dialysis (SLED). A Prospective Study on Feasibility of TPTD and Prediction of Successful Fluid Removal.

BACKGROUND: Acute kidney injury (AKI) is common in critically ill patients. AKI requires renal replacement therapy (RRT) in up to 10% of patients. Particularly during connection and fluid removal, RRT frequently impairs haemodyamics which impedes recovery from AKI. Therefore, "acute" connection with prefilled tubing and prolonged periods of RRT including sustained low efficiency dialysis (SLED) has been suggested. Furthermore, advanced haemodynamic monitoring using trans-pulmonary thermodilution (TPTD) and pulse contour analysis (PCA) might help to define appropriate fluid removal goals. OBJECTIVES, METHODS: Since data on TPTD to guide RRT are scarce, we investigated the capabilities of TPTD- and PCA-derived parameters to predict feasibility of fluid removal in 51 SLED-sessions (Genius; Fresenius, Germany; blood-flow 150 mL/min) in 32 patients with PiCCO-monitoring (Pulsion Medical Systems, Germany). Furthermore, we sought to validate the reliability of TPTD during RRT and investigated the impact of "acute" connection and of disconnection with re-transfusion on haemodynamics. TPTDs were performed immediately before and after connection as well as disconnection. RESULTS: Comparison of cardiac index derived from TPTD (CItd) and PCA (CIpc) before, during and after RRT did not give hints for confounding of TPTD by ongoing RRT. Connection to RRT did not result in relevant changes in haemodynamic parameters including CItd. However, disconnection with re-transfusion of the tubing volume resulted in significant increases in CItd, CIpc, CVP, global end-diastolic volume index GEDVI and cardiac power index CPI. Feasibility of the pre-defined ultrafiltration goal without increasing catecholamines by >10% (primary endpoint) was significantly predicted by baseline CPI (ROC-AUC 0.712; p = 0.010) and CItd (ROC-AUC 0.662; p = 0.049). CONCLUSIONS: TPTD is feasible during SLED. "Acute" connection does not substantially impair haemodynamics. Disconnection with re-transfusion increases preload, CI and CPI. The extent of these changes might be used as a "post-RRT volume change" to guide fluid removal during subsequent RRTs. CPI is the most useful marker to guide fluid removal by SLED.

Predictors of the accuracy of pulse-contour cardiac index and suggestion of a calibration-index: a prospective evaluation and validation study.

BACKGROUND: Cardiac Index (CI) is a key-parameter of hemodynamic monitoring. Indicator-dilution is considered as gold standard and can be obtained by pulmonary arterial catheter or transpulmonary thermodilution (TPTD; CItd). Furthermore, CI can be estimated by Pulse-Contour-Analysis (PCA) using arterial wave-form analysis (CIpc). Obviously, adjustment of CIpc to CItd initially improves the accuracy of CIpc. Despite uncertainty after which time accuracy of CIpc might be inappropriate, recalibration by TPTD is suggested after a maximum of 8 h. We hypothesized that accuracy of CIpc might not only depend on time to last TPTD, but also on changes of the arterial wave curve detectable by PCA itself. Therefore, we tried to prospectively characterize predictors of accuracy and precision of CIpc (primary outcome). In addition to "time to last TPTD" we evaluated potential predictors detectable solely by pulse-contour-analysis. Finally, the study aimed to develop a pulse-contour-derived "calibration-index" suggesting recalibration and to validate these results in an independent collective. METHODS: In 28 intensive-care-patients with PiCCO-monitoring (Pulsion Medical-Systems, Germany) 56 datasets were recorded. CIpc-values at baseline and after intervals of 1 h, 2 h, 4 h, 6 h and 8 h were compared to CItd derived from immediately subsequent TPTD. Results from this evaluation-collective were validated in an independent validation-collective (49 patients, 67 datasets). RESULTS: Mean bias values CItd-CIpc after different intervals ranged between -0.248 and 0.112 L/min/m(2). Percentage-error after different intervals to last TPTD ranged between 18.6% (evaluation, 2 h-interval) and 40.3% (validation, 6 h-interval). In the merged data, percentage-error was below 30% after 1 h, 2 h, 4 h and 8 h, and exceeded 30% only after 6 h. "Time to last calibration" was neither associated to accuracy nor to precision of CIpc in any uni- or multivariate analysis. By contrast, the height of CIpc and particularly changes in CIpc compared to last thermodilution-derived CItd(base) univariately and independently predicted the bias CItd-CIpc in both collectives. Relative changes of CIpc compared to CItd(base) exceeding thresholds derived from the evaluation-collective (-11.6% < CIpc-CItd(base)/CItd(base) < 7.4%) were confirmed as significant predictors of a bias |CItd-CIpc| ≥ 20% in the validation-collective. CONCLUSION: Recalibration triggered by changes of CIpc compared to CItd(base) derived from last calibration should be preferred to fixed intervals.

Fungal "colonisation" is associated with increased mortality in medical intensive care unit patients with liver cirrhosis.

OBJECTIVES: Patients with liver cirrhosis are at increased risk for fungal infections. However, distinction of fungal colonisation (FC) and invasive mycoses is difficult. Aim of this study was to analyse the impact of FC on mortality of cirrhotic ICU-patients. METHODS: Retrospective mortality analysis of a prospectively maintained database on 120 cirrhotic patients with and without FC. Comparison to 120 noncirrhotic controls matched for APACHE-II (24.9 ± 3.7 vs. 25.0 ± 2.6; p = 0.263). RESULTS: About 69/120 (58%) of patients with cirrhosis had FC. These patients had significantly higher APACHE-II score and mortality compared to cirrhotic patients without FC (27 ± 3 vs. 23 ± 4, p < 0.001; 78 vs. 35%, p < 0.001). In multivariate analysis, FC was independently (p = 0.047) associated to mortality. Mortality of noncirrhotic patients with FC (14/31; 45.2%) was not different to noncirrhotic controls without FC [28/89 (31.2%; p = 0.168)]. Similarly, in multivariate analysis of noncirrhotics, APACHE-II (p < 0.001), but not FC, was independently associated to mortality. Multiple regression analysis of all 240 cirrhotic and noncirrhotic patients demonstrated that APACHE-II (p < 0.001), cirrhosis (p = 0.001) and FC (p = 0.049) were independently associated with mortality. CONCLUSION: Fungal "colonisation" is independently associated to mortality in cirrhotic ICU-patients. Early antimycotic therapy should be considered in critically ill cirrhotic patients with FC.

Dose-intensified granulocyte-monocyte apheresis in therapy refractory ulcerative colitis.

Granulocyte-monocyte apheresis (GMA) is an emerging therapeutic option in active course of ulcerative colitis (UC). Appropriate GMA dose, including total number, frequency, and duration of the individual GMA session, is a matter of debate. It was the aim of the present study to evaluate the efficacy of a dose-intensified GMA regimen in patients with moderately to severely active UC. A prospective open-label, single-center study was performed in 10 patients with active UC (Rachmilewitz Clinical Activity Index [CAI] ≥ 8 points; Rachmilewitz Endoscopic Index ≥ 7 points). Patients had failed to improve after treatment with steroids and/or immunomodulators. GMA was performed twice weekly for 2 h to a maximum of 10 sessions. In each GMA session, the adsorber was changed after 1 h of treatment time. Four patients achieved remission with a CAI ≤ 4 points. Three patients had a response with an improvement of CAI of ≥3 points. Three patients showed no benefit from GMA. The quality of life score determined by the inflammatory bowel disease questionnaire-Deutschland increased by 26 points in median. First and second filters had similar efficiency in granulocyte and monocyte adsorption. No major adverse effects were observed. Dose-intensified GMA as reported in this study provided an encouraging short-term response rate of 70% in patients with moderately to severely active UC not responding to standard steroid or immunomodulator therapy. Although all patients relapsed not later than 16 weeks, GMA might be useful to reduce steroid and immunomodulator usage, or to delay surgery in this patient group.

Effects of paracentesis on hemodynamic parameters and respiratory function in critically ill patients.

BACKGROUND: Ascites is a major and common complication of liver cirrhosis. Large or refractory ascites frequently necessitates paracentesis. The aim of our study was to investigate the effects of paracentesis on hemodynamic and respiratory parameters in critically ill patients. METHODS: Observational study comparing hemodynamic and respiratory parameters before and after paracentesis in 50 critically ill patients with advanced hemodynamic monitoring. 28/50 (56%) required mechanical ventilation.Descriptive statistics are presented as mean ± standard deviation for normally distributed data and median, range, and interquartile range (IQR) for non-normally distributed data. Comparisons of hemodynamic and respiratory parameters before and after paracentesis were performed by Wilcoxon signed-rank tests. Bivariate relations were assessed by Spearman's correlation coefficient and univariate regression analyses. RESULTS: Median amount of ascites removed was 5.99 L (IQR, 3.33-7.68 L). There were no statistically significant changes in hemodynamic parameters except a decrease in mean arterial pressure (-7 mm Hg; p = 0.041) and in systemic vascular resistance index (-116 dyne·sec/cm5/m2; p = 0.016) when measured 2 hours after paracentesis. In all patients, oxygenation ratio (PaO2/FiO2; median, 220 mmHg; IQR, 161-329 mmHg) increased significantly when measured immediately (+58 mmHg; p = 0.001), 2 hours (+9 mmHg; p = 0.004), and 6 hours (+6 mmHg); p = 0.050) after paracentesis. In mechanically ventilated patients, lung injury score (cumulative points without x-ray; median, 6; IQR, 4-7) significantly improved immediately (5; IQR, 4-6; p < 0.001), 2 hours (5; IQR, 4-7; p = 0.003), and 6 hours (6; IQR 4-6; p = 0.012) after paracentesis. CONCLUSION: Paracentesis in critically ill patients is safe regarding circulatory function and is related to immediate and sustained improvement of respiratory function.

Prediction of contrast-induced nephropathy in patients with serum creatinine levels in the upper normal range by cystatin C: a prospective study in 374 patients.

OBJECTIVE: Preexisting renal impairment is a risk factor for contrast-induced nephropathy (CIN). In patients with creatinine in the upper normal level, cystatin C might be a more sensitive predictor of CIN than creatinine. Therefore, in this study, we investigated the usefulness of cystatin C to predict CIN. SUBJECTS AND METHODS: In 400 consecutive patients with creatinine baseline levels between 0.8 and 1.3 mg/dL undergoing coronary angiography (n = 200) or CT (n = 200), baseline values of cystatin C, creatinine, blood urea nitrogen (BUN) and risk factors of CIN were determined. Creatinine was also assessed 24 and 48 hours after contrast administration. RESULTS: Creatinine significantly (p < 0.001) increased after 24 hours and 48 hours compared with baseline (1.06 ± 0.28 and 1.07 ± 0.28 vs 0.99 ± 0.18 mg/dL). Fifty-three of 373 evaluable patients (14.2%) had an increase in creatinine of ≥ 25% or ≥ 0.5 mg/dL within 48 hours. CIN according to this definition was significantly more frequent after intraarterial contrast administration (38/190, 20%) compared with IV contrast administration (15/183, 8.2%; p = 0.001). CIN was predicted by baseline cystatin C (area under the receiver operating characteristic [ROC] curve [AUC], 0.715; p < 0.001), whereas creatinine, creatinine clearance, and BUN were not predictive. The best predictive capabilities were provided by cystatin C/creatinine-ratio (AUC, 0.826; p < 0.001). Multivariate regression analysis showed that intraarterial contrast administration (p = 0.002) and higher baseline cystatin C (p < 0.001) combined with low creatinine (p = 0.044) were independently associated with higher increases in creatinine within 48 hours after contrast administration. CONCLUSION: CIN in patients with creatinine within the upper normal range is significantly more frequent after intraarterial than after IV contrast administration. In these patients, renal impairment after contrast administration is independently predicted by cystatin C and cystatin C/creatinine-ratio, whereas BUN and creatinine were not predictive.

Effects of red blood cell transfusion on hemodynamic parameters: a prospective study in intensive care unit patients.

BACKGROUND: The aim of the study was to investigate the effect of red blood cell (RBC) transfusion on hemodynamic parameters including transpulmonary thermodilution (TPTD)-derived variables. METHODS: We compared hemodynamic parameters obtained before and after RBC transfusion (2 RBC units) in 34 intensive care unit (ICU) patients. RESULTS: Directly after RBC transfusion, we observed a significant increase in hematocrit (28 ± 3 vs. 22 ± 2%, p < 0.001), hemoglobin (9.4 ± 0.9 vs. 7.6 ± 0.8 g/dL, p < 0.001), arterial oxygen content (CaO2) (12.2 ± 1.2 vs. 9.9 ± 1.0 mL/dL, p < 0.001), and oxygen delivery (DO2) (1073 ± 369 vs. 934 ± 288 mL/min, p < 0.001) compared with baseline. Cardiac output (CO) (8.89 ± 3.06 vs. 9.42 ± 2.75 L/min, p = 0.020), cardiac index (CI) (4.53 ± 1.36 vs. 4.82 ± 1.21 L/min/m², p = 0.016), and heart rate (91 ± 16 vs. 95 ± 14 bpm, p = 0.007) were significantly lower following RBC transfusion while no significant change in stroke volume (SV) was observed. Mean arterial pressure (MAP) (median 87 vs. 78 mmHg, p < 0.001) and systemic vascular resistance index (SVRI) (median 1212 vs. 1103 dyn*s*cm⁻5*m², p = 0.001) significantly increased directly after RBC transfusion. Global end-diastolic volume index (GEDVI), extravascular lung water index (EVLWI), and pulmonary vascular permeability index (PVPI) did not significantly change. CONCLUSIONS: In ICU patients, the transfusion of 2 RBC units induces a significant decrease in CO and CI because of a significant decrease in heart rate (while SV remains unchanged). Despite the decrease in CO, DO2 significantly increases because of a significant increase in CaO2. In addition, RBC transfusion results in a significant increase in MAP and SVRI. No significant changes in TPTD-parameters reflecting cardiac preload (GEDVI), pulmonary edema (EVLWI), and pulmonary vascular permeability (PVPI) are observed following RBC transfusion.

Prediction of fluid responsiveness in patients admitted to the medical intensive care unit.

PURPOSE: Accurate prediction of fluid responsiveness is of importance in the treatment of patients admitted to the intensive care unit (ICU). We investigated whether physical examination, central venous pressure (CVP), central venous oxygen saturation (ScvO2), passive leg raising (PLR) test, and transpulmonary thermodilution (TPTD)-derived parameters can predict volume responsiveness in patients admitted to the ICU. MATERIALS AND METHODS: In this prospective study, structured clinical examination, measurement of CVP and ScvO2, a PLR test, and TPTD measurements were performed in 31 patients. A fluid challenge test was performed in 24 patients (fluid responsiveness was defined as a cardiac index [CI] increase of ≥ 15%). RESULTS: Physical examination, CVP, ScvO2, the PLR test, and the TPTD-derived volumetric preload parameter global end-diastolic volume index showed poor prognostic capabilities regarding prediction of fluid responsiveness. Twenty-nine percent of patients were fluid responsive. There was a statistically significant correlation between the fluid challenge-induced increase in CI and changes in global end-diastolic volume index (r = 0.666, P < .001). In only 17% of patients, CI did not increase after fluid loading. CONCLUSIONS: Prediction of fluid responsiveness is difficult using physical examination, CVP, ScvO2, PLR maneuver, or TPTD-derived variables in critically ill patients. A volume challenge test should be considered for the assessment of fluid responsiveness in critically ill patients admitted to the ICU.

Continuous intravenous administration of vancomycin in medical intensive care unit patients.

PURPOSE: The aim of this study was to evaluate continuous vancomycin infusion (contV) in intensive care unit patients. MATERIALS AND METHODS: A retrospective study in 164 patients treated with contV was conducted. They were compared with 75 patients treated with intermittent vancomycin infusion. RESULTS: The median duration of vancomycin therapy in the contV group was 6 (5%-95% percentile range, 2-21) days. The median daily vancomycin dose in the contV group was 960 (526-1723) mg, resulting in a median serum vancomycin plateau concentration of 19.8 (9.8-29.4) mg/L (target: 15-25 mg/L). The contV administration regime was sufficient regarding achievement of the target serum vancomycin concentration. However, in the contV group, serum vancomycin levels were frequently in a subtherapeutic range on treatment days 1 (44%), 2 (29%), and 3 (23%). In the contV group, serum vancomycin concentration determinations per treatment day were performed significantly less often compared with the intermittent vancomycin infusion group (0.38 [0.15-0.75] vs 0.43 [0.22-1.00], P = .041). CONCLUSIONS: In medical intensive care unit patients, contV is sufficient to achieve target serum vancomycin concentrations. Because contV frequently resulted in subtherapeutic drug levels on the first days of therapy, a higher loading or starting dose might be necessary.

Continuous venovenous hemodialysis with regional citrate anticoagulation in patients with liver failure: a prospective observational study.

INTRODUCTION: Liver failure patients might be at risk for citrate accumulation during continuous venovenous hemodialysis (CVVHD) with regional citrate anticoagulation. The aim of this study was to investigate the predictive capability of baseline liver function parameters regarding citrate accumulation, expressed as an increase in the calcium total/calcium ionized (Ca(tot)/Ca(ion)) ratio ≥ 2.5, and to describe the feasibility of citrate CVVHD in liver failure patients. METHODS: We conducted a prospective observational study in medical ICU patients treated in a German university hospital. We performed 43 CVVHD runs using citrate for regional anticoagulation in 28 critically ill patients with decompensated liver cirrhosis or acute liver failure (maximum of two CVVHD runs per patient). Liver function was characterized before CVVHD using laboratory parameters, calculation of Child-Pugh and Model of End-stage Liver Disease scores, and determination of the plasma disappearance rate of indocyanine green. In addition to blood gas analysis, we measured total calcium and citrate in serum at baseline and after definitive time points for each CVVHD run. RESULTS: Accumulation of citrate in serum correlated with an increase in the Ca(tot)/Ca(ion) ratio. Although the critical upper threshold of Ca(tot)/Ca(ion) ratio ≥ 2.5 was exceeded 10 times in seven different CVVHD runs, equalization of initial metabolic acidosis was possible without major disturbances of acid-base and electrolyte status. Standard laboratory liver function parameters showed poor predictive capabilities regarding citrate accumulation in terms of an elevated Ca(tot)/Ca(ion) ratio ≥ 2.5. In contrast, serum lactate ≥ 3.4 mmol/l and prothrombin time ≤ 26% predicted an increase in the Ca(tot)/Ca(ion) ratio ≥ 2.5 with high sensitivity (86% for both lactate and prothrombin time) and specificity (86% for lactate, 92% for prothrombin time). CONCLUSIONS: Despite substantial accumulation of citrate in serum, CVVHD with regional citrate anticoagulation seems feasible in patients with severely impaired liver function. Citrate accumulation in serum is reflected by an increase in the Ca(tot)/Ca(ion) ratio. To identify patients at risk for citrate accumulation in terms of a Ca(tot)/Ca(ion) ratio ≥ 2.5, baseline serum lactate (threshold ≥ 3.4 mmol/l) and prothrombin time (threshold ≤ 26%) may be useful for risk prediction in daily clinical practice. Careful monitoring of electrolytes and acid-base status is mandatory to ensure patient safety.

Prediction of extubation failure in medical intensive care unit patients.

PURPOSE: The purpose of this study was to evaluate prediction factors for extubation failure (need for reintubation within 48 hours) in medical intensive care unit patients. MATERIALS AND METHODS: Sixty-one patients extubated after mechanical ventilation for more than 48 hours were included in the study. A retrospective analysis of medical records and a prospectively maintained database on respiratory parameters was conducted. RESULTS: Low serum anion gap (P = .001), low serum anion gap corrected for serum albumin (P = .010), and low arterial partial pressure of oxygen (Pao(2))/fraction of inspired oxygen (Fio(2)) ratio (P = .032) were significantly associated with extubation failure. Binary logistic regression analysis revealed low uncorrected and corrected serum anion gap (P = .006 and P = .025, respectively; odds ratio, 0.59 for both) and low Pao(2)/Fio(2) ratio (P = .038; odds ratio, 0.99) as risk factors for extubation failure. Regarding extubation failure, receiver operating characteristic curve (ROC) analysis demonstrated good predictive capabilities of serum anion gap (ROC area under the curve, 0.835; P = .004; cutoff, 7.7 mEq/L; sensitivity, 70.4%; specificity, 85.7%) and corrected serum anion gap (ROC area under the curve, 0.808; P = .009; cutoff, 8.8 mEq/L; sensitivity, 87.5%; specificity, 71.4%). A significantly higher risk for extubation failure was observed in patients with serum anion gap 5.2 mEq/L or less (relative risk, 8.8; 95% confidence interval, 2.4-32.4; P = .004) and corrected serum anion gap 8.6 mEq/L or less (relative risk, 10.0; 95% confidence interval, 2.2-44.9; P = .004). CONCLUSIONS: Low preextubation serum anion gap values and low preextubation Pao(2)/Fio(2) ratio might help to predict extubation failure in medical intensive care unit patients.

Advanced hemodynamic monitoring before and after transjugular intrahepatic portosystemic shunt: implications for selection of patients--a prospective study.

PURPOSE: To investigate immediate and short-term effects of transjugular intrahepatic portosystemic shunt (TIPS) on cardiocirculatory, hepatic, and renal function and characterize predictors for TIPS outcome in terms of organ function after TIPS. MATERIALS AND METHODS: This prospective study was approved by the ethics committee at a university hospital and was conducted in a medical intensive care unit. Informed consent was obtained. Twenty patients with indication for TIPS were enrolled. Monitoring of hemodynamic and hepatic function (transpulmonary thermodilution, indocyanine green plasma disappearance rate [ICG-PDR]) was performed. Biochemical markers of organ function were obtained. Statistical analysis (Wilcoxon test, Spearman correlation, multivariate linear regression analysis, receiver operating characteristic [ROC] analysis) was performed. RESULTS: After TIPS, central venous pressure (median, 11 vs 15 cm H(2)O; P < .001), cardiac index (3.4 vs 3.8 L/min/m(2); P = .001), and global end-diastolic volume index (GEDVI) (726 vs 775 mL/m(2); P = .003) increased significantly. Portosystemic pressure gradient (28 vs 11 cm H(2)O; P < .001) and systemic vascular resistance index (1610 vs 1384 dyn · sec · cm(-5) · m(2); P = .015) decreased significantly. Creatinine (1.1 vs 1.1 mg/dL; P = .008) and blood urea nitrogen (BUN) (27 vs 21 mg/dL; P = .006) decreased significantly. Bilirubin (1.8 vs 2.2 mg/dL; P = .032) and international normalized ratio (1.4 vs 1.5; P = .022) increased significantly. ICG-PDR significantly deteriorated after TIPS (P = .006). Higher baseline creatinine was independently associated with a decrease in creatinine after TIPS (R = 0.816, P < .001). ROC analysis identified baseline BUN (P = .026, area under ROC curve [AUC] = 0.818), cystatin C (P = .033, AUC = 0.805), and creatinine (P = .052, AUC = 0.779) as predictors of a decrease in creatinine of 0.5 mg/dL or greater and/or 25% or greater. An increase in bilirubin of 1 mg/dL or greater 1 week after TIPS was significantly associated with high baseline BUN (P = .007, AUC = 0.893) and high central venous pressure (P = .040, AUC = 0.800). Lower baseline alanine aminotransferase (P = .002, AUC = 1.000) and cardiac power index · GEDVI (P = .005, AUC = 0.960) predicted favorable TIPS outcome (creatinine decrease of ≥ 0.2 mg/dL without model for end-stage liver disease score increase of more than one point). CONCLUSION: Patients with renal insufficiency, compensated hepatocellular function, decreased cardiac preload, and decreased cardiac performance benefit most from TIPS.

Computed tomography to estimate cardiac preload and extravascular lung water. A retrospective analysis in critically ill patients.

BACKGROUND: In critically ill patients intravascular volume status and pulmonary edema need to be quantified as soon as possible. Many critically ill patients undergo a computed tomography (CT)-scan of the thorax after admission to the intensive care unit (ICU). This study investigates whether CT-based estimation of cardiac preload and pulmonary hydration can accurately assess volume status and can contribute to an early estimation of hemodynamics. METHODS: Thirty medical ICU patients. Global end-diastolic volume index (GEDVI) and extravascular lung water index (EVLWI) were assessed using transpulmonary thermodilution (TPTD) serving as reference method (with established GEDVI/EVLWI normal values). Central venous pressure (CVP) was determined. CT-based estimation of GEDVI/EVLWI/CVP by two different radiologists (R1, R2) without analyzing software. Primary endpoint: predictive capabilities of CT-based estimation of GEDVI/EVLWI/CVP compared to TPTD and measured CVP. Secondary endpoint: interobserver correlation and agreement between R1 and R2. RESULTS: Accuracy of CT-estimation of GEDVI (< 680, 680-800, > 800 mL/m2) was 33%(R1)/27%(R2). For R1 and R2 sensitivity for diagnosis of low GEDVI (< 680 mL/m2) was 0% (specificity 100%). Sensitivity for prediction of elevated GEDVI (> 800 mL/m2) was 86%(R1)/57%(R2) with a specificity of 57%(R1)/39%(R2) (positive predictive value 38%(R1)/22%(R2); negative predictive value 93%(R1)/75%(R2)). Estimated CT-GEDVI and TPTD-GEDVI were significantly different showing an overestimation of GEDVI by the radiologists (R1: mean difference ± standard error (SE): 191 ± 30 mL/m2, p < 0.001; R2: mean difference ± SE: 215 ± 37 mL/m2, p < 0.001). CT GEDVI and TPTD-GEDVI showed a very low Lin-concordance correlation coefficient (ccc) (R1: ccc = +0.20, 95% CI: +0.00 to +0.38, bias-correction factor (BCF) = 0.52; R2: ccc = -0.03, 95% CI: -0.19 to +0.12, BCF = 0.42). Accuracy of CT estimation in prediction of EVLWI (< 7, 7-10, > 10 mL/kg) was 30% for R1 and 40% for R2. CT-EVLWI and TPTD-EVLWI were significantly different (R1: mean difference ± SE: 3.3 ± 1.2 mL/kg, p = 0.013; R2: mean difference ± SE: 2.8 ± 1.1 mL/kg, p = 0.021). Again ccc was low with -0.02 (R1; 95% CI: -0.20 to +0.13, BCF = 0.44) and +0.14 (R2; 95% CI: -0.05 to +0.32, BCF = 0.53). GEDVI, EVLWI and CVP estimations of R1 and R2 showed a poor interobserver correlation (low ccc) and poor interobserver agreement (low kappa-values). CONCLUSIONS: CT-based estimation of GEDVI/EVLWI is not accurate for predicting cardiac preload and extravascular lung water in critically ill patients when compared to invasive TPTD-assessment of these variables.

In vivo characterization of endothelial cell activation in a transgenic mouse model of Alzheimer's disease.

Alzheimer's disease (AD) is the most common cause of dementia worldwide. AD is characterized by an excessive cerebral amyloid deposition leading to degeneration of neurons and eventually to dementia. It has been shown by epidemiological studies that cardiovascular drugs with an anti-angiogenic effect can influence the outcome of AD patients. Therefore, it has been speculated that in AD angiogenesis in the brain vasculature may play an important role. Here we report that in the brain of APP23 mice--a transgenic model of AD--after deposition of amyloid in blood vessels endothelial cell activation occurs in an age-dependent manner. Amyloid deposition is followed by the expression of beta3-integrin, a specific marker molecule of activated endothelium. The beta3-integrin expression is restricted to amyloid-positive vessels. Moreover, homogenates of the brains of APP23 mice induced the formation of new vessels in an in vivo angiogenesis assay. Vessel formation could be blocked by the VEGF antagonist SU 4312 as well as by statins, suggesting that these drugs may interfere with endothelial cell activation in AD. In conclusion our results indicate that amyloid deposition in the vasculature leads to endothelial cell apoptosis and endothelial cell activation, which can be modulated by anti-angiogenic drugs.