First clinical experience in 14 patients treated with ADVOS: a study on feasibility, safety and efficacy of a new type of albumin dialysis.

BACKGROUND: Liver failure (LF) is associated with prolonged hospital stay, increased cost and substantial mortality. Due to the limited number of donor organs, extracorporeal liver support is suggested as an appealing concept to "bridge to transplant" or to avoid transplant in case of recovery. ADVanced Organ Support (ADVOS) is a new type of albumin dialysis, that provides rapid regeneration of toxin-binding albumin by two purification circuits altering the binding capacities of albumin by biochemical (changing of pH) and physical (changing of temperature) modulation of the dialysate. It was the aim of this study to evaluate feasibility, efficacy and safety of ADVOS in the first 14 patients ever treated with this procedure. METHODS: Patients included suffered from acute on chronic LF (n = 9) or "secondary" LF (n = 5) which resulted from non-hepatic diseases such as sepsis. The primary endpoint was the change of serum bilirubin, creatinine and serum BUN levels before and after the first treatment with ADVOS. The Wilcoxon Signed Rank test for paired samples was used to analyze the data. RESULTS: A total of 239 treatments (1 up to 101 per patient) were performed in 14 patients (6 female, 8 male). Mean age 54 ± 13; MELD-score 34 ± 7; CLIF-SOFA 15 ± 3. Serum bilirubin levels were significantly decreased by 32% during the first session (26.0 ± 15.4 vs. 17.7 ± 10.5 mg/dl; p = 0.001). Similarly, serum creatinine (2.2 ± 0.8 vs. 1.6 ± 0.7 mg/dl; p = 0.005) and serum BUN (49.4 ± 23.3 vs. 31.1 ± 19.7 mg/dl; p = 0.003), were significantly lowered by 27% and 37%, respectively. None of the treatment sessions had to be interrupted due to side effects related to the procedure. CONCLUSION: ADVOS efficiently eliminates water- and protein-bound toxins in humans with LF. ADVOS is feasible in patients with advanced LF which is emphasized by a total number of more than 100 treatment sessions in one single patient.

Consistency of cardiac function index and global ejection fraction with global end-diastolic volume in patients with femoral central venous access for transpulmonary thermodilution: a prospective observational study.

Global ejection fraction (GEF) and cardiac function index (CFI) are transpulmonary thermodilution (TPTD)-derived indices of the systolic function. Their validity relies on an accurate determination of the global end-diastolic volume (GEDV). Due to an overestimation of GEDV using a femoral central venous catheter (CVC) a correction formula for indexed GEDV (GEDVI) has been implemented in the latest PiCCO™-algorithm. However, a recent study demonstrated that correction for femoral CVC does not pertain to pulmonary vascular permeability index PVPI, which is calculated of extravascular lung water EVLW and GEDV. Therefore, it was the aim of our study to evaluate, if GEF and CFI are corrected for femoral CVC. In ten adult ICU-patients with PiCCO™-monitoring, ten triplicate TPTDs were performed within 30 h. 95 complete data sets were analyzed, if a GEDV corrected for CVC site was applied to derive CFI and GEF. Therefore, we compared displayed values CFIdisplayed and GEFdisplayed to CFIcalculated and GEFcalculated, which were calculated from displayed GEDV, cardiac output and stroke volume. GEDVcalculated derived from division of GEDVI by predicted body surface area did not substantially differ from GEDVdisplayed (1448 ± 414 ml vs. 1447 ± 416 ml), which suggests a correction of GEDV for CVC site. However, CFIdisplayed was significantly lower than CFIcalculated (3.8 ± 1.6/min vs. 5.1 ± 1. 8/min: p < 0.001), suggesting that CFIdisplayed is based on an uncorrected GEDV. By contrast, GEFcalculated (23.1 ± 8.7 %) was not substantially different from GEFdisplayed (22.4 ± 8.6 %). Although GEDV and GEF are corrected for femoral CVC site, this does not apply to CFI. However, all indices derived from GEDV should be calculated consistently.

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.

Pulmonary vascular permeability index and global end-diastolic volume: are the data consistent in patients with femoral venous access for transpulmonary thermodilution: a prospective observational study.

BACKGROUND: Transpulmonary thermodilution (TPTD) derived parameters are used to direct fluid management in ICU-patients. Extravascular lung water EVLW and its ratio to pulmonary blood volume (pulmonary vascular permeability index PVPI) have been associated with mortality. In single indicator TPTD pulmonary blood volume (PBV) is estimated to be 25% of global end-diastolic volume (GEDV). A recent study demonstrated marked overestimation of GEDV indexed to body-surface area (BSA; GEDVI) when using a femoral central venous catheter (CVC) for indicator injection due to the additional volume measured in the vena cava inferior. Therefore, a correction formula derived from femoral TPTD and biometric data has been suggested. Consequence, one of the commercially available TPTD-devices (PiCCO; Pulsion Medical Systems, Germany) requires information about CVC site. Correction of GEDVI for femoral CVC can be assumed. However, there is no data if correction also pertains to unindexed GEDV, which is used for calculation of PBV and PVPI. Therefore, we investigated, if also GEDV, PBV and PVPI are corrected by the new PiCCO-algorithm. METHODS: In this prospective study 110 triplicate TPTDs were performed within 30 hours in 11 adult ICU-patients with PiCCO-monitoring and femoral CVC. We analyzed if the femoral TPTD correction formula for GEDVI was also applied to correct GEDV. Furthermore, we compared PVPIdisplayed to PVPIcalculated which was calculated as EVLWdisplayed/(0.25*GEDVdisplayed). RESULTS: Multiplication of GEDVIdisplayed by BSA resulted in GEDVcalculated which was not significantly different to GEDVdisplayed (1459 ± 365 mL vs. 1459 ± 366 mL) suggesting that correction for femoral indicator injection also pertains to GEDVdisplayed. However, PVPIdisplayed was significantly lower than PVPIcalculated (1.64 ± 0.57 vs. 2.27 ± 0.72; p < 0.001). In addition to a bias of -0.64 ± 0.22 there was a percentage error of 22%. Application of the correction formula suggested for GEDVI to PVPIdisplayed reduced the bias of PVPIdisplayed compared to EVLW/PBV from -0.64 ± 0.22 to -0.10 ± 0.05 and the percentage error from 22% to 4%. CONCLUSIONS: Correction for femoral CVC in the PiCCO-device pertains to both GEDVIdisplayed and GEDVdisplayed, but not to PVPIdisplayed. To provide consistent information, PVPI should be calculated based on GEDVcorrected in case of femoral CVC.

Volume assessment in patients with necrotizing pancreatitis: a comparison of intrathoracic blood volume index, central venous pressure, and hematocrit, and their correlation to cardiac index and extravascular lung water index.

OBJECTIVE: Volume depletion and/or increased hematocrit are associated with poor prognosis in necrotizing pancreatitis. Several studies suggest that intrathoracic blood volume index (ITBI) might be superior to central venous pressure (CVP) with regard to preload assessment. Therefore, the aim of our study was to evaluate the predictive value of CVP and hematocrit with regard to ITBI, and to correlate these parameters to cardiac index (CI). DESIGN: Prospective study. SETTING: Medical intensive care unit, university hospital. PATIENTS AND INTERVENTIONS: Within 24 hrs of intensive care unit-admission, 96 hemodynamic measurements using the PiCCO system were performed in 24 patients with necrotizing pancreatitis. MAIN RESULTS: Mean CVP (12.11 +/- 5.97 mm Hg; median 11.5 normal: 1-9 mm Hg) was elevated, whereas mean ITBI (822.8 +/- 157.0 mL/m2; median 836 mL/m2; normal: 850-1000 mL/m2) was decreased. Fifty-one of 96 ITBI values were decreased (prevalence of hypovolemia of 53%). No CVP value was decreased. Fifty-three CVP measurements were elevated despite simultaneous ITBI levels indicating a normal or decreased preload. Sensitivity, specificity, positive predictive value, and negative predictive value of CVP with regard to volume depletion (ITBI <850 mL/m2), were 0%, 100%, 0%, and 47%, respectively. An increase in hematocrit (hematocrit >40% [female] or >44% [male]) was found in 11 of 51 measurements with decreased ITBI. Sensitivity, specificity, positive predictive value, and negative predictive value of an increase in hematocrit with regard to volume depletion according to ITBI were 22%, 82%, 58%, and 48%, respectively. ITBI and delta-ITBI significantly correlated to CI and delta-CI (r = .566, p < 0.001; r = .603, p < 0.001), respectively. CVP and delta-CVP did not correlate to CI and delta-CI, respectively. There was a significant correlation between ITBI and extravascular lung water index (r = .392; p < 0.001), but no correlation between CVP and extravascular lung water index (r = .074; p = 0.473). CONCLUSIONS: Volume depletion according to ITBI was found in more than half the patients. The predictive values of CVP and hematocrit with regard to volume depletion were low. ITBI and its changes significantly correlated to CI and its changes, which was not observed for CVP and delta-CVP. Therefore, ITBI appears to be more appropriate for volume management in necrotizing pancreatitis than CVP or hematocrit.

Impact of large volume paracentesis on respiratory parameters including transpulmonary pressure and on transpulmonary thermodilution derived hemodynamics: A prospective study.

INTRODUCTION: Appropriate mechanical ventilation and prevention of alveolar collaps is mainly dependent on transpulmonary pressure TPP. TPP is assessed by measurement of esophageal pressure EP, largely influenced by pleural and intraabdominal pressure IAP. Consecutively, TPP-guided ventilation might be particularly useful in patients with high IAP. This study investigates the impact of large volume paracentesis LVP on TPP, EP, IAP as well as on hemodynamic and respiratory function in patients with liver cirrhosis and tense ascites. MATERIAL AND METHODS: We analysed 23 LVP-procedures in 11 cirrhotic patients ventilated with the AVEA Viasys respirator (CareFusion, USA) which is capable to measure EP via an esophageal tube. RESULTS: LVP of a mean volume of 4826±1276 mL of ascites resulted in marked increases in inspiratory (17.9±8.9 vs. 5.4±13.3 cmH2O; p<0.001) as well as expiratory TPP (-3.0±4.7 vs. -15.9±10.9 cmH2O; p<0.001; primary endpoint). In parallel, the inspiratory (2.4±8.7 vs. 14.1±14.5 cmH2O; p<0.001) and expiratory EP (12.4±6.0 vs. 24.9±11.3 cmH2O; p<0.001) significantly decreased. The effects were most pronounced for the release of the first 500 mL of ascites. LVP evoked substantial decreases in IAP and central venous pressure CVP. By contrast, mean arterial pressure, cardiac index, global end-diastolic volume index, extravascular lung water index and systemic vascular resistance index did not change. Among the respiratory parameters we observed an increase in paO2/FiO2 (247.7±60.9 vs. 208.3±46.8 mmHg; p<0.001) and a decrease in Oxygenation Index OI (4.8±2.0 vs. 5.8±3.1 cmH2O/mmHg; p = 0.002). Tidal volume (510±100 vs. 452±113 mL; p = 0.008) and dynamic respiratory system compliance Cdyn (46.8±15.9 vs. 35.1±14.6 mL/cmH20; p<0.001) increased, whereas paCO2 (47.3±10.7 vs. 51.2±12.3mmHg; p = 0.046) and the respiratory rate decreased (17.1±7.3 vs. 19.6±7.8 min-1; p = 0.010). CONCLUSIONS: In mechanically ventilated patients with decompensated cirrhosis, intraabdominal hypertension resulted in a substantially decreased TPP despite PEEP-setting according to the ARDSNet. In these patients LVP markedly increased TPP and improved respiratory function in parallel with a decline of EP. Furthermore, LVP induced a decrease in IAP and CVP, while other hemodynamic parameters did not change.