IntroductionNeurological prognostic factors after cardiopulmonary resuscitation (CPR) in patients with cardiac arrest (CA) as early and accurately as possible are urgently needed to determine therapeutic strategies after successful CPR. In particular, serum levels of protein neuron-specific enolase (NSE) and S-100B are considered promising candidates for neurological predictors, and many investigations on the clinical usefulness of these markers have been published. However, the design adopted varied from study to study, making a systematic literature review extremely difficult. The present review focuses on the following three respects for the study design: definitions of outcome, value of specificity and time points of blood sampling.MethodsA Medline search of literature published before August 2008 was performed using the following search terms: "NSE vs CA or CPR", "S100 vs CA or CPR". Publications examining the clinical usefulness of NSE or S-100B as a prognostic predictor in two outcome groups were reviewed. All publications met with inclusion criteria were classified into three groups with respect to the definitions of outcome; "dead or alive", "regained consciousness or remained comatose", and "return to independent daily life or not". The significance of differences between two outcome groups, cutoff values and predictive accuracy on each time points of blood sampling were investigated.ResultsA total of 54 papers were retrieved by the initial text search, and 24 were finally selected. In the three classified groups, most of the studies showed the significance of differences and concluded these biomarkers were useful for neurological predictor. However, in view of blood sampling points, the significance was not always detected. Nevertheless, only five studies involved uniform application of a blood sampling schedule with sampling intervals specified based on a set starting point. Specificity was not always set to 100%, therefore it is difficult to indiscriminately assess the cut-off values and its predictive accuracy of these biomarkers in this meta analysis.ConclusionsIn such circumstances, the findings of the present study should aid future investigators in examining the clinical usefulness of these markers and determination of cut-off values.
While evidence supporting the hypothesis that blood purification improve outcome in septic acute kidney injury (AKI) has not been established, many physicians hope to improve outcome in septic AKI by blood purification. Elucidation of the pathophysiology of sepsis has revealed close involvement of humoral mediators, including cytokines, pathogen-associated molecular patterns, and alarmins, in the development of severe sepsis. Removal of substances by blood purification involves three major principles, namely filtration, dialysis (diffusion), and adsorption. Multiple large randomized controlled trials (RCTs) of high-volume hemofiltration (HVHF) for patients with AKI were conducted, but failed to prove the clinical efficacy of HVHF. Blood purification for the removal of mediators through dialysis and filtration using a high cutoff (HCO) membrane hemofilter has not also been established. Furthermore, a HCO membrane hemofilter shares a common problem with HVHF, which is excessive removal of useful substances, such as antimicrobial agents and/or nutrients. Accordingly, continuous hemodiafiltration using cytokine-adsorbing hemofilters (CAH-CHDF) such as polymethylmethacrylate (PMMA) and AN69ST membrane hemofilters has been attracting attention recently. In this review, we report recent findings regarding these old hemofilters with new applications. Although the number of in vitro and in vivo studies conducted to date has been limited, the studies suggest a possibility that these modalities are useful particularly for the treatment of septic shock and septic AKI. CAH-CHDF is expected to be recognized globally as a treatment of septic shock and septic AKI in the near future.
To investigate changes in protein expression by proteomic analysis in the sera of patients with sepsis and to identify new biomarkers of sepsis. A total of 45 consecutive patients with severe sepsis or septic shock (sepsis group), 22 healthy volunteers, and 23 patients undergoing off-pump coronary artery bypass grafting (control group). Serum samples from eight patients of each group underwent proteomic analysis involving removal of 12 major proteins and subsequent reversed-phase high-performance liquid chromatography fractionation and one-dimensional electrophoresis. The intensity of 41 bands (with 12 proteins identified) increased and that of 42 bands (with 22 proteins identified) decreased in the sepsis group. Results of proteomic analysis successfully validated by Western blotting and/or enzyme-linked immunosorbent assay for three proteins (YKL-40, lipocalin 2, and S100A9) increased in the sepsis group as well as two proteins (retinol-binding protein, vitamin D-binding protein) decreased. Serum YKL-40 levels (sYKL-40) on intensive care unit (ICU) admission were assessed by enzyme-linked immunosorbent assay between the two groups; resulting YKL-40 was significantly higher in the sepsis group (P < 0.001). Furthermore, sYKL-40 on ICU admission was significantly higher in patients with positive blood culture (P < 0.005), patients with septic shock (P < 0.05), and patients requiring continuous hemodiafiltration (P < 0.05) or hydrocortisone replacement therapy (P < 0.005) during subsequent treatment. A positive correlation between sYKL-40 and blood IL-6 level on ICU admission was noted in the sepsis group (r = 0.465, P < 0.01). YKL-40 identified by proteomic analysis is considered as a biomarker of sepsis. However, further investigation is needed to clarify its roles and clinical usefulness as a biomarker.
Successful weaning from VA-ECMO was predicted by post-PCI TIMI flow grade, MAP at 4 hours, and serum lactate at 24 hours after VA-ECMO initiation in patients of AMI complicated by CA. Furthermore, in patients who failed to wean from ECMO, LVEF did not recover within 48 hours. In such patients, adjunctive use of other circulatory mechanical devices must be considered.
Patients receiving extracorporeal membrane oxygenation (ECMO) often require continuous renal replacement therapy (CRRT). The intra-circuit pressure of adult ECMO usually deviates from the physiological range. We investigated the use of CRRT connected to an ECMO circuit with physiological intra-circuit pressures (0-150 mmHg, defined as the "safety range") using an in vitro experiment involving a water-filled ECMO circuit. The intra-circuit pressure pre-pump, post-pump, and post-oxygenator were measured while varying the height of the pump or ECMO flow. The bypass conduit pressure and distance from the post-oxygenator port were measured to find the "safety point", where the bypass pressure remained within the safety range. Both drainage and return limbs of the CRRT machine were connected to the safety point and the inlet and outlet pressures of the hemofilter were recorded while varying the ECMO and CRRT flow. The pre-pump pressure only remained within the safety range for heights >75 cm (ECMO flow = 4 L/min) or ECMO flow <3.5 L min (height = 50 cm). The post-pump and post-oxygenator pressure was generally outside of the safety range. The bypass pressure decreased according to the distance from the post-oxygenator port and the safety point was found at 60 or 75 cm (in a 90-cm length conduit) regardless of ECMO flow. The hemofilter inlet and outlet pressures remained within the safety range for all conditions of ECMO and CRRT flow, findings validated in clinical cases. The bypass conduit within an ECMO circuit can be connected to a CRRT machine safely under physiological pressures in adult patients receiving ECMO.
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