Penetration of Isavuconazole in Ascites Fluid of Critically Ill Patients.

Fungal peritonitis is a life-threatening condition which is not only difficult to diagnose, but also to treat. Following recent guidelines, echinocandins and azoles are the recommended antimycotics for the management of intra-abdominal Candida spp. infections, with a favor for echinocandins in critically ill patients. However, the new extended spectrum triazole isavuconazole also has a broad spectrum against Candida spp. Data on its target-site penetration are sparse. Therefore, we assessed isavuconazole concentrations and penetration ratios in ascites fluid of critically ill patients. Obtaining of Isavuconazole plasma and ascites fluid levels as well penetration ratios using paracentesis in critically ill patients. Isavuconazole concentrations were quantified in human plasma and ascites by a liquid chromatography/tandem mass spectrometry (LC-MS/MS) method. Isavuconazole concentrations in plasma and ascites fluid were measured in sixteen critically ill patients. Isavuconazol levels in ascites fluid (1.06 µg/mL) were lower than plasma levels (3.08 µg/mL). Penetration ratio was 36%. In two out of sixteen patients, Candida spp., in detail C. glabrata and C. tropicalis, could be isolated. Cmax/MIC Ratio in plasma of 560 for C. glabrata and 2166 for C. tropicalis could be observed. Following our results, isavuconazole penetrates into ascites. Successful treatment in Candida spp. peritonitis depends on pathogen susceptibility.

NUTRIC and Modified NUTRIC are Accurate Predictors of Outcome in End-Stage Liver Disease: A Validation in Critically Ill Patients with Liver Cirrhosis.

Malnutrition in critically ill patients with cirrhosis is a frequent but often overlooked complication with high prognostic relevance. The Nutrition Risk in Critically ill (NUTRIC) score and its modified variant (mNUTRIC) were established to assess the nutrition risk of intensive care unit patients. Considering the high mortality of cirrhosis in critically ill patients, this study aims to evaluate the discriminative ability of NUTRIC and mNUTRIC to predict outcome. We performed a retro-prospective evaluation in 150 Caucasian cirrhotic patients admitted to our ICU. Comparative prognostic analyses between NUTRIC and mNUTRIC were assessed in 114 patients. On ICU admission, a large proportion of 65% were classified as high NUTRIC (6-10) and 75% were categorized as high mNUTRIC (5-9). High nutritional risk was linked to disease severity and poor outcome. NUTRIC was moderately superior to mNUTRIC in prediction of 28-day mortality (area under curve 0.806 vs. 0.788) as well as 3-month mortality (area under curve 0.839 vs. 0.819). We found a significant association of NUTRIC and mNUTRIC with MELD, CHILD, renal function, interleukin 6 and albumin, but not with body mass index. NUTRIC and mNUTRIC are characterized by high prognostic accuracy in critically ill patients with cirrhosis. NUTRIC revealed a moderate advantage in prognostic ability compared to mNUTRIC.

Vitamin D Deficiency Is Highly Prevalent in Critically Ill Patients and a Risk Factor for Mortality: A Prospective Observational Study Comparing Noncirrhotic Patients and Patients With Cirrhosis.

INTRODUCTION: A 25-hydroxyvitamin D, 25(OH)D, deficiency is common among critically ill patients and correlated with increased mortality. Furthermore, deficiency is associated with advanced liver disease. However, there are no studies available comparing the dimensions and consequences of a 25(OH)D deficiency between patients with and without liver cirrhosis in the setting of intensive care units (ICUs). This study focuses on differences in 25(OH)D status between critically ill noncirrhosis patients and patients with cirrhosis (primary end point), hypothesizing that deficiency and its impact on mortality risk are even more pronounced in patients with cirrhosis. METHODS: We performed a prospective observational study of 176 patients (noncirrhosis patients, N = 114; patients with cirrhosis, N = 62) with a laboratory assessment of 25(OH)D on ICU admission and survival analyses after 180 days. RESULTS: On admission, 55% of patients showed a severe deficiency, 25(OH)D <10 ng/mL, and a further 23% moderate deficiency (10-19 ng/mL). The overall median level of 25(OH)D was 8.0 (5.0-18.0) ng/mL (10.5 [6.0-21.3] in noncirrhosis patients vs 7.0 [4.8-10.0] in patients with cirrhosis; P < .001). We found extremely low levels particularly in patients without prior vitamin D supplementation (6.0 [4.0-7.5] in patients with cirrhosis vs 8.0 [5.0-12.0] ng/mL in noncirrhosis patients; P = .004). Vitamin D status correlated inversely with the sequential organ failure assessment, acute and physiology chronic health evaluation, model of end-stage liver disease, and Child-Pugh scores. Survival analyses categorized 25(OH)D levels <10 ng/mL as a high-risk factor for mortality 180 days after admission (hazard ratio [HR]: 2.45, 95% confidence interval [CI] = 1.60-3.70; P < .001). In patients with cirrhosis, a severe deficiency (<10 ng/mL) involved a significantly higher mortality risk than in noncirrhosis patients (HR: 2.30, 95% CI = 1.39-3.82; P = .001). In cases of admission levels ≥10 ng/mL, however, mortality risk was similar between patients with cirrhosis and noncirrhosis patients (HR: 1.08, 95% CI = 0.43-2.73; P = .873). CONCLUSIONS: Hypovitaminosis D is a highly frequent disorder in critically ill patients admitted to ICU. A severe deficiency with levels <10 ng/mL is a high risk factor for increased mortality, especially in patients with cirrhosis.

Influence of Sustained Low-Efficiency Dialysis Treatment on Isavuconazole Plasma Levels in Critically Ill Patients.

Isavuconazole plasma concentrations were measured before and after sustained low-efficiency dialysis (SLED) treatment in 22 critically ill adult patients with probable invasive aspergillosis and underlying hematological malignancies. Isavuconazole levels were significantly lower after SLED treatment (5.73 versus 3.36 µg/ml; P < 0.001). However, even after SLED treatment, isavuconazole concentrations exceeded the in vivo MICs for several relevant Aspergillus species.

Large-volume paracentesis effects plasma disappearance rate of indo-cyanine green in critically ill patients with decompensated liver cirrhosis and intraabdominal hypertension.

BACKGROUND: Ascites is a major complication of decompensated liver cirrhosis. Intraabdominal hypertension and structural alterations of parenchyma involve decisive changes in hepatosplanchnic blood flow. Clearance of indo-cyanine green (ICG) is mainly dependent on hepatic perfusion and hepatocellular function. As a consequence, plasma disappearance rate of ICG (ICG-PDR) is rated as a useful dynamic parameter of liver function. This study primarily evaluates the impact of large-volume paracentesis (LVP) on ICG-PDR in critically ill patients with decompensated cirrhosis. Additionally, it describes influences on intraabdominal pressure (IAP), abdominal perfusion pressure (APP), hepatic blood flow, hemodynamic and respiratory function. METHODS: We analyzed LVP in 22 patients with decompensated liver cirrhosis. ICG-PDR was assessed by using noninvasive LiMON technology (Pulsion® Medical Systems; Maquet Getinge Group), and hepatic blood flow was analyzed by color-coded duplex sonography. RESULTS: Paracentesis of a median volume of 3450 mL ascites evoked significant increases of ICG-PDR from 3.6 (2.8-4.6) to 5.1 (3.9-6.2)%/min (p < 0.001). Concomitantly, we observed a raise in "ICG-Clearance" from 99 (73.5-124.5) to 104 (91-143.5) mL/min/m2 (p = 0.005), while circulating blood volume index was unchanged [2412 (1983-3025) before paracentesis vs. 2409 (1997-2805) mL/m2, p = 0.734]. Sonography revealed a significant impact of paracentesis on hepatic blood flow: Hepatic artery resistance index dropped from 0.74 (0.68-0.75) to 0.68 (0.65-0.71) (p < 0.001) and maximum flow velocity in hepatic vein increased from 24 (17-30) to 30 (22-36) cm/s (p < 0.001). Consistent with previous studies, paracentesis caused significant decreases in IAP from 19.0 (15.0-20.3) to 11.0 (8.8-12.3) mmHg (p < 0.001) and central venous pressure from 22.5 (17.8-29.0) to 17.5 (12.8-24.0) mmHg (p < 0.001) with inverse increases in APP from 63.0 (56.8-69.5) to 71.0 (65.5-78.5) mmHg (p < 0.001). Changes in ICG-PDR were concomitant with changes in IAP (r = - 0.602) and APP (r = 0.576). Moreover, we found a substantial improvement in respiratory function. By contrast, hemodynamic parameters assessed by transpulmonary thermodilution, serum bilirubin and international normalized ratio did not change after paracentesis. CONCLUSION: Critically ill patients with decompensated cirrhosis and elevated IAP showed dramatically impaired ICG-PDR. Paracentesis evoked an improvement in ICG-PDR in parallel with a decreased IAP and an increased APP, while conventional parameters of liver function did not change. This effect on ICG-PDR is mainly referable to a relief of intraabdominal hypertension and changes in hepatosplanchnic blood flow.

Comparison of pulmonary vascular permeability index PVPI and global ejection fraction GEF derived from jugular and femoral indicator injection using the PiCCO-2 device: A prospective observational study.

BACKGROUND: Transpulmonary thermodilution (TPTD) is used to derive cardiac output CO, global end-diastolic volume GEDV and extravascular lung water EVLW. To facilitate interpretation of these data, several ratios have been developed, including pulmonary vascular permeability index (defined as EVLW/(0.25*GEDV)) and global ejection fraction ((4*stroke volume)/GEDV). PVPI and GEF have been associated to the aetiology of pulmonary oedema and systolic cardiac function, respectively. Several studies demonstrated that the use of femoral venous access results in a marked overestimation of GEDV. This also falsely reduces PVPI and GEF. One of these studies suggested a correction formula for femoral venous access that markedly reduced the bias for GEDV. Consequently, the last PiCCO-algorithm requires information about the CVC, and correction for femoral access has been shown. However, two recent studies demonstrated inconsistencies of the last PiCCO algorithm using incorrected GEDV for PVPI, but corrected GEDV for GEF. Nevertheless, these studies were based on mathematical analyses of data displayed in a total of 15 patients equipped with only a femoral, but not with a jugular CVC. Therefore, this study compared PVPI_fem and GEF_fem derived from femoral TPTD to values derived from jugular indicator injection in 25 patients with both jugular and femoral CVCs. METHODS: 54 datasets in 25 patients were recorded. Each dataset consisted of three triplicate TPTDs using the jugular venous access as the gold standard and the femoral access with (PVPI_fem_cor) and without (PVPI_fem_uncor) information about the femoral indicator injection to evaluate, if correction for femoral GEDV pertains to PVPI_fem and GEF_fem. RESULTS: PVPI_fem_uncor was significantly lower than PVPI_jug (1.48±0.47 vs. 1.84±0.53; p<0.001). Similarly, PVPI_fem_cor was significantly lower than PVPI_jug (1.49±0.46 vs. 1.84±0.53; p<0.001). This is explained by the finding that PVPI_fem_uncor was not different to PVPI_fem_cor (1.48±0.47 vs. 1.49±0.46; n.s.). This clearly suggests that correction for femoral CVC does not pertain to PVPI. GEF_fem_uncor was significantly lower than GEF_jug (20.6±5.1% vs. 25.0±6.1%; p<0.001). By contrast, GEF_fem_cor was not different to GEF_jug (25.6±5.8% vs. 25.0±6.1%; n.s.). Furthermore, GEF_fem_cor was significantly higher than GEF_fem_uncor (25.6±5.8% vs. 20.6±5.1%; p<0.001). This finding emphasizes that an appropriate correction for femoral CVC is applied to GEF_fem_cor. The extent of the correction (25.5/20.6; 124%) for GEF and the relation of PVPI_jug/PVPI_fem_uncor (1.84/1.48; 124%) are in the same range as the ratio of GEDVI_fem_uncor/GEDVI_fem_cor (1056ml/m2/821mL/m2; 129%). This further emphasizes that GEF, but not PVPI is corrected in case of femoral indicator injection. CONCLUSIONS: Femoral indicator injection for TPTD results in significantly lower values for PVPI and GEF. While the last PiCCO algorithm appropriately corrects GEF, the correction is not applied to PVPI. Therefore, GEF-values can be used in case of femoral CVC, but PVPI-values are substantially underestimated.

In-parallel connected intermittent hemodialysis through ECMO does not affect hemodynamic parameters derived from transpulmonary thermodilution.

INTRODUCTION: We report a case of renal replacement therapy (RRT) during extracorporeal membrane oxygenation (ECMO) via a single venous access and analyze the feasibility of transpulmonary thermodilution (TPTD) for hemodynamic monitoring. CASE REPORT: ECMO and RRT connected into the ECMO-extracorporeal circuit were performed via a single venous access because of multiple venous thromboses. An indicator for TPTD and pulse contour analysis (PCA) was applied into the central venous catheter (CVC) placed in the right vena jugularis. TPTD and PCA demonstrated comparable cardiac index. DISCUSSION: Congruent data for TPTD and PCA could be observed during TPTD and PCA measurements before ECMO, after ECMO and during ECMO and RRT. This might be explained by high blood flow having the lowest impact on TPTD by venous drainage in the femoral vein/distal vena cava and the TPTD indicator injection using the jugular CVC, as reported in our case. CONCLUSION: Hemodynamic monitoring using TPTD and PCA during ECMO/RRT is feasible and provides reliable results.