Extracorporeal adsorption of protective and toxic bile acids and bilirubin in patients with cholestatic liver dysfunction: a prospective study.

BACKGROUND: The release of toxic bile acids (BAs) in the blood of critically ill patients with cholestatic liver dysfunction might lead to the damage of various organs. Their extracorporeal elimination using the cytokine adsorber Cytosorb® (CS) (adsorption of especially hydrophobic molecules < 60 kDa) might be promising, but data proving a potential adsorption are missing so far. METHODS: The prospective Cyto-SOVLE study (NCT04913298) included 20 intensive care patients with cholestatic liver dysfunction, continuous kidney replacement therapy, total bilirubin concentration > 10 mg/dl and the application of CS into the dialysis circuit. Bilirubin and different BAs were measured pre- and post-CS at defined timepoints (10 min, 1, 3, 6, and 12 h after initiation). Relative reduction (RR, %) was calculated with: [Formula: see text]. RESULTS: The median RR for total and conjugated bilirubin after initiation was - 31.8% and - 30.3%, respectively, and decreased to - 4.5% and - 4.8% after 6 h. A high initial RR was observed for the toxic BAs GCA (- 97.4%), TCA (- 94.9%), GCDCA (- 82.5%), and TCDCA (- 86.0%), decreasing after 6 h to - 32.9%, - 32.7%, - 12.8%, and - 14.3%, respectively. The protective hydrophilic BAs showed a comparable RR after initiation (UDCA: - 77.7%, GUDCA: - 83.0%, TUDCA: - 91.3%) dropping after 6 h to - 7.4%, - 8.5%, and - 12.5%, respectively. CONCLUSIONS: Cytosorb® can adsorb bilirubin and toxic as well as protective BAs. However, a fast saturation of the adsorber resulting in a rapid decrease of the RR was observed. Furthermore, no relevant difference between hydrophobic toxic and hydrophilic protective BAs was detected regarding the adsorption amount. The clinical benefit or harm of the BA adsorption needs to be evaluated in the future.

The effect of cytosorb® application on kidney recovery in critically ill patients with severe rhabdomyolysis: a propensity score matching analysis.

Severe rhabdomyolysis frequently results in acute kidney injury (AKI) due to myoglobin accumulation with the need of kidney replacement therapy (KRT). The present study investigated whether the application of Cytosorb® (CS) led to an increased rate of kidney recovery in patients with KRT due to severe rhabdomyolysis. Adult patients with a myoglobin-concentration >10,000 ng/ml and KRT were included from 2014 to 2021. Exclusion criteria were chronic kidney disease and CS-treatment before study inclusion. Groups 1 and 2 were defined as KRT with and without CS, respectively. The primary outcome parameter was independence from KRT after 30 days. Propensity score (PS) matching was performed (predictors: myoglobin, SAPS-II, and age), and the chi2-test was used. 35 pairings could be matched (mean age: 57 vs. 56 years; mean myoglobin: 27,218 vs. 26,872 ng/ml; mean SAPS-II: 77 vs. 76). The probability of kidney recovery was significantly (p = .04) higher in group 1 (31.4 vs. 11.4%, mean difference: 20.0%, odds ratio (OR): 3.6). Considering patients who survived 30 days, kidney recovery was also significantly (p = .03) higher in patients treated with CS (61.1 vs. 23.5%, mean difference: 37.6%, OR: 5.1). In conclusion, the use of CS might positively affect renal recovery in patients with severe rhabdomyolysis. A prospective randomized controlled trial is needed to confirm this hypothesis.

Serum linezolid concentrations are reduced in critically ill patients with pulmonary infections: A prospective observational study.

RATIONALE: The concentration-time profile of linezolid varies considerably in critically ill patients. Question of interest is, if the site of infection influences linezolid serum concentrations. METHODS: 68 critically ill patients, treated with linezolid, were included. The concentration-time-profile for linezolid was determined using maximum a-posteriori predictions. A trough concentration (Cmin) between 2 and 10 mg/L was defined as the target. A generalized linear model (GLM) was established to evaluate potential covariates. RESULTS: The indications for linezolid therapy were in descending order: peritonitis (38.2%), pneumonia (25.0%), infectious acute respiratory distress syndrome (ARDS) (19.1%), and other non-pulmonary infection (17.7%). 27.2 and 7.9% of Cmin were subtherapeutic and toxic, respectively. In the GLM, ARDS (mean: -2.1 mg/L, CI: -3.0 to -1.2 mg/L) and pneumonia (mean: -2.2 mg/L, CI: -2.8 to -1.6 mg/L) were significant (p < 0.001) determinants of Cmin. Patients with ARDS (mean: 2.3 mg/L, 51.2% subtherapeutic, 0.0% toxic) and pneumonia (mean: 3.5 mg/L, 41.5% subtherapeutic, 7.7% toxic) had significantly (p < 0.001) lower Cmin than those with peritonitis (mean: 5.5 mg/L, 14.4% subtherapeutic, 9.3% toxic) and other non-pulmonary infection (mean: 5.2 mg/L, 3.3% subtherapeutic, 16.5% toxic). CONCLUSION: Linezolid serum concentrations are reduced in patients with pulmonary infections. Future studies should investigate if other linezolid thresholds are needed in those patients due to linezolid pooling in patients´ lung.