Sublingual Microcirculatory Evaluation of Extracorporeal Hemoadsorption with CytoSorb® in Abdominal Sepsis: A Case Report.

Cytokemia is associated with microcirculatory alterations often with persistent loss of coherence between the micro- and macrocirculation, linked to organ failure and poor outcome of septic patients. Addition of a hemoadsorbant filter to an extracorporeal circuit next to conventional treatment of septic shock results in the hematological clearance of cytokines, hypothetically leading to normalization of the microcirculation and thus organ perfusion. Bedside sublingual microcirculatory assessment using handheld vital microscopy allows real-time direct visualization of the microcirculation and its response to therapy. This is demonstrated in the present case report of an 83-year-old man admitted to our intensive care unit after surgical repair of a colonic perforation for fecal soiling after a low anterior resection for a rectum carcinoma, with leakage of bowel content at the resection site. The clinical course of this patient can be described as having undergone adequate surgical treatment taking away the source of the disease, followed by optimal support including antibiotic treatment in the ICU. However, during the course of his stay in the ICU, his condition deteriorated with symptoms consistent with septic shock. Our report shows that the addition of a hemoadsorbent (CytoSorb) to the continuous renal replacement therapy circuit was associated with an improvement in the condition of our severely ill patient with abdominal sepsis. Parallel to the clinical improvement of our patient, the functional parameters of the microcirculation also showed improvement suggesting that such a noninvasive real-time evaluation of the status of the microcirculation may be a sensitive diagnostic tool to monitor the effectiveness of hemoadsorbent therapy.

Improved Survival beyond 28 Days up to 1 Year after CytoSorb Treatment for Refractory Septic Shock: A Propensity-Weighted Retrospective Survival Analysis.

BACKGROUND AND AIMS: It is currently unknown whether CytoSorb treatment for septic shock improves long-term survival beyond 28 days from intensive care unit (ICU) admission and which factors determine outcome. METHODS: This was a long-term follow-up retrospective analysis of patients with septic shock who were treated with continuous renal replacement therapy (CRRT) + CytoSorb (n = 67) or CRRT alone (n = 49). These patients were previously analyzed for 28-day mortality. The primary outcome was the time to long-term all-cause mortality. Factors associated with time to event were analyzed both weighted by stabilized inverse probability of treatment weights (sIPTW) as well as unweighted stratified by therapy received. RESULTS: The median follow-up for the total cohort was 30 days (interquartile range [IQR]: 5-334, maximum 1,059 days) after ICU admission and 333 days (IQR: 170-583) for those who survived beyond 28 days (n = 59). Survival beyond 28 days was sustained up to 1 year after ICU admission for both treatment regimens: 80% (standard error [SE] 7%) vs. 87% (SE 7%), for CytoSorb vs. CRRT, respectively, p = 0.853. By sIPTW, CytoSorb was significantly associated with long-term outcome compared to CRRT (adjusted hazard ratio [aHR] 0.59, 95% confidence interval [CI] 0.37-0.93, p = 0.025). Independent factors associated with long-term outcome in CytoSorb-treated patients were baseline log10 lactate levels (aHR 5.1, p = 0.002), age in the presence of comorbidity (aHR 2.60, p = 0.013), and presence of abdominal sepsis (aHR 0.34, p = 0.004). A lactate level above 6.0 mmol/L at the start of CytoSorb therapy had a positive predictive value of 79% for mortality (p = 0.013). CONCLUSIONS: Survival is achieved with CytoSorb and CRRT for patients with septic shock beyond 28 days from ICU admission and may be improved for CytoSorb treatment. Lactate levels above 6.0 mmol/L at the start of CytoSorb therapy are predictive of worse outcome with high specificity and positive predictive value.

Hemoadsorption with CytoSorb shows a decreased observed versus expected 28-day all-cause mortality in ICU patients with septic shock: a propensity-score-weighted retrospective study.

BACKGROUND AND AIMS: Innovative treatment modalities have not yet shown a clinical benefit in patients with septic shock. To reduce severe cytokinaemia, CytoSorb as an add-on to continuous renal replacement therapy (CRRT) showed promising results in case reports. However, there are no clinical trials investigating outcomes. METHODS: In this investigator-initiated retrospective study, patients with septic shock were treated with CRRT + CytoSorb (n = 67) or CRRT alone (n = 49). The primary outcome was the 28-day all-cause mortality rate. Patients were weighted by stabilized inverse probability of treatment weights (sIPTW) to overcome differences in baseline characteristics. RESULTS: At the start of therapy, CytoSorb-treated patients had higher lactate levels (p < 0.001), lower mean arterial pressure (p = 0.007) and higher levels of noradrenaline (p < 0.001) compared to the CRRT group. For CytoSorb, the mean predicted mortality rate based on a SOFA of 13.8 (n = 67) was 75% (95%CI 71-79%), while the actual 28-day mortality rate was 48% (mean difference - 27%, 95%CI - 38 to - 15%, p < 0.001). For CRRT, based on a SOFA of 12.8 (n = 49), the mean predicted versus observed mortality was 68% versus 51% (mean difference - 16.9% [95%CI - 32.6 to - 1.2%, p = 0.035]). By sIPTW analysis, patients treated with CytoSorb had a significantly lower 28-day mortality rate compared to CRRT alone (53% vs. 72%, respectively, p = 0.038). Independent predictors of 28-day mortality in the CytoSorb group were the presence of pneumosepsis (adjusted odds ratio [aOR] 5.47, p = 0.029), higher levels of lactate at the start of CytoSorb (aOR 1.15, p = 0.031) and older age (aOR per 10 years 1.67, p = 0.034). CONCLUSIONS: CytoSorb was associated with a decreased observed versus expected 28-day all-cause mortality. By IPTW analysis, intervention with CytoSorb may be associated with a decreased all-cause mortality at 28 days compared to CRRT alone.

Improved Guideline Adherence and Reduced Brain Dysfunction After a Multicenter Multifaceted Implementation of ICU Delirium Guidelines in 3,930 Patients.

OBJECTIVES: Implementation of delirium guidelines at ICUs is suboptimal. The aim was to evaluate the impact of a tailored multifaceted implementation program of ICU delirium guidelines on processes of care and clinical outcomes and draw lessons regarding guideline implementation. DESIGN: A prospective multicenter, pre-post, intervention study. SETTING: ICUs in one university hospital and five community hospitals. PATIENTS: Consecutive medical and surgical critically ill patients were enrolled between April 1, 2012, and February 1, 2015. INTERVENTIONS: Multifaceted, three-phase (baseline, delirium screening, and guideline) implementation program of delirium guidelines in adult ICUs. MEASUREMENTS AND MAIN RESULTS: The primary outcome was adherence changes to delirium guidelines recommendations, based on the Pain, Agitation and Delirium guidelines. Secondary outcomes were brain dysfunction (delirium or coma), length of ICU stay, and hospital mortality. A total of 3,930 patients were included. Improvements after the implementation pertained to delirium screening (from 35% to 96%; p < 0.001), use of benzodiazepines for continuous sedation (from 36% to 17%; p < 0.001), light sedation of ventilated patients (from 55% to 61%; p < 0.001), physiotherapy (from 21% to 48%; p < 0.001), and early mobilization (from 10% to 19%; p < 0.001). Brain dysfunction improved: the mean delirium duration decreased from 5.6 to 3.3 days (-2.2 d; 95% CI, -3.2 to -1.3; p < 0.001), and coma days decreased from 14% to 9% (risk ratio, 0.5; 95% CI, 0.4-0.6; p < 0.001). Other clinical outcome measures, such as length of mechanical ventilation, length of ICU stay, and hospital mortality, did not change. CONCLUSIONS: This large pre-post implementation study of delirium-oriented measures based on the 2013 Pain, Agitation, and Delirium guidelines showed improved health professionals' adherence to delirium guidelines and reduced brain dysfunction. Our findings provide empirical support for the differential efficacy of the guideline bundle elements in a real-life setting and provide lessons for optimization of guideline implementation programs.

Effects of Copper Oxide Nanoparticles on Antioxidant Enzyme Activities and on Tissue Accumulation of Oreochromis niloticus.

Accumulation of copper oxide nanoparticles (CuO NPs) in gill, liver and muscle tissues of Oreochromis niloticus and its effects on superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx) activities in gill and liver tissues were studied after exposing the fish to 20 µg/L Cu over 15 days. Copper levels and enzyme activities in tissues were determined using spectrophotometric (ICP-AES and UV) techniques respectively. No mortality was observed during the experiments. Copper levels increased in gill and liver tissues of O. niloticus compared to control when exposed to CuO NPs whereas exposure to metal had no effect on muscle level at the end of the exposure period. Highest accumulation of copper was observed in liver while no accumulation was detected in muscle tissue. SOD, CAT activities decreased and GPx activity increased in gill and liver tissues when exposed to CuO NPs.

Accumulation of Copper in Gill, Liver, Spleen, Kidney and Muscle Tissues of Clarias gariepinus Exposed to the Metal Singly and in Mixture with Chitosan.

Accumulation of copper (Cu), applied singly and in mixture with chitosan (CT), in gill, liver, spleen, kidney and muscle tissues of Clarias gariepinus was studied after exposing the fish to no Cu (control), 5 ppm Cu, 5 ppm Cu + 75 ppm CT mixture over 1, 7 and 15 days. Metal levels in tissues were determined using an ICP-AES spectrophotometer. No mortality was observed during the experiments. Highest accumulation of Cu was observed in liver while lowest accumulation was observed in muscle tissue. Exposure to Cu-CT mixture decreased Cu accumulation in liver at all exposure periods and in kidney on the 15th day compared to Cu alone. Exposure to Cu alone and Cu-CT mixture had no effect on Cu accumulation in spleen or muscle tissue. Copper accumulation increased in gill tissue compared to control when exposed to Cu alone at all exposure periods, and exposure to the Cu-CT mixture significantly increased Cu accumulation in this tissue at all exposure periods compared to Cu alone.

The intensive care infection score - a novel marker for the prediction of infection and its severity.

BACKGROUND: The prediction of infection and its severity remains difficult in the critically ill. A novel, simple biomarker derived from five blood-cell derived parameters that characterize the innate immune response in routine blood samples, the intensive care infection score (ICIS), could be helpful in this respect. We therefore compared the predictive value of the ICIS with that of the white blood cell count (WBC), C-reactive protein (CRP) and procalcitonin (PCT) for infection and its severity in critically ill patients. METHODS: We performed a multicenter, cluster-randomized, crossover study in critically ill patients between January 2013 and September 2014. Patients with a suspected infection for which blood cultures were taken by the attending intensivist were included. Blood was taken at the same time for WBC, ICIS, CRP and PCT measurements in the control study periods. Results of imaging and cultures were collected. Patients were divided into groups of increasing likelihood of infection and invasiveness: group 1 without infection or with possible infection irrespective of cultures, group 2 with probable or microbiologically proven local infection without blood stream infection (BSI) and group 3 with BSI irrespective of local infection. Septic shock was assessed. RESULTS: In total, 301 patients were enrolled. CRP, PCT and ICIS were higher in groups 2 and 3 than group 1. The area under the receiver operating characteristic curve (AUROC) for the prediction of infection was 0.70 for CRP, 0.71 for PCT and 0.73 for ICIS (P < 0.001). For the prediction of septic shock the AUROC was 0.73 for CRP, 0.85 for PCT and 0.76 for ICIS. These AUROC did not differ from each other. CONCLUSION: The data suggest that the ICIS is potentially useful for the prediction of infection and its severity in critically ill patients, non-inferiorly to CRP and PCT. In contrast to CRP and PCT, the ICIS can be determined routinely without extra blood sampling and lower costs, yielding results within 15 minutes. TRIAL REGISTRATION: ClinicalTrials.gov identifier: ID NCT01847079 . Registered on 24 April 2013.