Early induction of direct hemoperfusion with a polymyxin-B immobilized column is associated with amelioration of hemodynamic derangement and mortality in patients with septic shock.

This study was conducted to clarify the effectiveness of induction timing of direct hemoperfusion with a polymyxin-B immobilized column (PMX-DHP) for amelioration of hemodynamic derangement and outcome in patients with septic shock. Suspected Gram-negative septic shock patients who received PMX-DHP therapy from January 2010 to December 2014 in our ICU were enrolled in this study. The patients were divided into two groups that received PMX-DHP therapy within 8 h (early group) and more than 8 h (late group) from catecholamine administration. Changes in catecholamine dose [catecholamine index (CAI)], catecholamine dose/mean arterial pressure [catecholamine index pressure (CAIP)], PaO2/FiO2 and PEEP level were determined at the start of and 24 h after the start of PMX-DHP therapy. Ventilator-free days (VFD), ICU-free days (IFD), 28-day and hospital mortality were also determined. There were no significant differences in patients' characteristics between the two groups. CAI and CAIP were significantly decreased in the early group. PaO2/FiO2 was not changed whereas PEEP level in the early group was significantly decreased during PMX-DHP therapy. IFD and VFD were not different in the two groups. Mortality at 28 days was significantly improved in the early group. Endotoxin acts as an early mediator in sepsis patients with suspected Gram-negative infection. Earlier induction of PMX-DHP therapy as in our study is closely associated with earlier weaning from hemodynamic derangement and with improvement of mortality. Therefore, early induction of PMX-DHP therapy is recommended for the treatment of septic shock in patients with presumed Gram-negative infection.

Effect of prone positioning on cannula function and impaired oxygenation during extracorporeal circulation.

Prone ventilation is an effective method for improving oxygenation in patients with acute respiratory failure. However, in extracorporeal circulation, there is a risk of cannula-related complications when changing the position. In this study, we investigated cannula-related complications when changing position for prone ventilation and the effect of prone ventilation on impaired oxygenation in patients who underwent extracorporeal membrane oxygenation (ECMO). The study subjects were patients who underwent prone ventilation during ECMO in the period from 2004 to 2011. Indication for prone ventilation was the presence of dorsal infiltration shown by lung computed tomography. Factors investigated were cannula insertion site, dislodgement or obstruction of the cannula, malfunction of vascular access and unplanned dislodgement of the catheters when changing position. Mean arterial pressure, PaO2/FiO2, PEEP level, blood flow and rotation speed of the pump were also determined before and after position change. Five patients were selected as study subjects. The mean duration of prone positioning was 15.3 ± 0.5 h. Strict management during position changes prevented cannula-related complications in the patients who underwent extracorporeal circulation. There were no significant changes in mean arterial pressure, PEEP level, blood flow and rotation speed of the pump when changing position. Low PaO2/FiO2 prior to prone ventilation was significantly increased after supine to prone and then prone to supine position. Prone positioning to improve impaired oxygenation is a safe procedure and not a contraindication in patients receiving extracorporeal circulation.

Association between Extended Meropenem Regimen and Achievement of Aggressive PK/PD in Patients Receiving Continuous Renal Replacement Therapy for Septic AKI.

Aggressive pharmacokinetic (PK)/pharmacodynamic (PD) targets have shown better microbiological eradication rates and a lower propensity to develop resistant strains than conservative targets. We investigated whether meropenem blood levels, including aggressive PK/PD, were acceptable in terms of efficacy and safety using a meropenem regimen of 1 g infusion every 8 h over 3 h in patients undergoing continuous renal replacement therapy (CRRT) for septic acute kidney injury (AKI). Aggressive PK/PD targets were defined as the percentage of time that the free concentration (%fT) > 4 × minimal inhibitory concentration (MIC), the toxicity threshold was defined as a trough concentration >45 mg/L, and the percentage of achievement at each MIC was evaluated. The 100% fT > 4 × MIC for a pathogen with an MIC of 0.5 mg/L was 89%, and that for a pathogen with an MIC of 2 mg/L was 56%. The mean steady-state trough concentration of meropenem was 11.9 ± 9.0 mg/L and the maximum steady-state trough concentration was 29.2 mg/L. Simulations using Bayesian estimation showed the probability of achieving 100% fT > 4 × MIC for up to an MIC of 2 mg/L for the administered administration via continuous infusion at 3 g/24 h. We found that an aggressive PK/PD could be achieved up to an MIC of 0.5 mg/L with a meropenem regimen of 1 g infused every 8 h over 3 h for patients receiving CRRT for septic AKI. In addition, the risk of reaching the toxicity range with this regimen is low. In addition, if the MIC was 1-2 mg/L, the simulation results indicated that aggressive PK/PD can be achieved by continuous infusion at 3 g/24 h without increasing the daily dose.

Evaluation of pre- and post-dilution continuous veno-venous hemofiltration on leukocyte and platelet function in patients with sepsis.

OBJECTIVE:: We investigated the differences in biocompatibility pre- and post-dilution during continuous veno-venous hemofiltration in patients with sepsis, focusing on leukocyte and platelet function. PATIENTS AND METHODS:: Subjects were 12 patients with septic shock who underwent veno-venous hemofiltration for acute kidney injury between March 2016 and September 2017. The first six patients received pre-dilution veno-venous hemofiltration, and the next six patients received post-dilution veno-venous hemofiltration. The blood flow rate and filtration flow rate for veno-venous hemofiltration using a polysulfone hemofilter were set to 150 and 35 mL/min, respectively. Leukocyte and platelet counts were determined at 0 and 24 h after veno-venous hemofiltration commencement. Serum interleukin-6 and interleukin-10 levels, the induction rates of regulatory T cells, the expression rate of monocyte HLA-DR, neutrophil phagocytic and sterilizing ability, and platelet P-selectin expression rate were determined at 0, 6, and 24 h after veno-venous hemofiltration commencement. RESULTS:: There were no significant differences in patient characteristics between the two groups. Serum interleukin-6 decreased over time during pre- and post-dilution veno-venous hemofiltration. Serum interleukin-10 levels decreased during pre-dilution veno-venous hemofiltration, but remained unchanged during post-dilution veno-venous hemofiltration. The Treg and platelet P-selectin expression rates significantly increased at 24 h compared to 0 h during post-dilution veno-venous hemofiltration. Neutrophil phagocytic ability at 24 h was significantly decreased compared to that at 0 h during post-dilution veno-venous hemofiltration. No significant changes in leukocyte and platelet function were observed during pre-dilution veno-venous hemofiltration. CONCLUSION:: Pre-dilution veno-venous hemofiltration demonstrates superior biocompatibility in terms of decreased leukocyte function and platelet activation in septic shock patients with acute kidney injury.

Experimental and Clinical Evaluation of Predilution and Postdilution Continuous Venovenous Hemofiltration on Clearance Characteristics.

We compared the clearance characteristics of low-to-high molecular weight substances during pre-and postdilution continuous venovenous hemofiltration (CVVH) in experimental and clinical conditions. Experimental circuits for pre- and postdilution CVVH were prepared using a test solution containing creatinine (110 Da), inulin (5,000 Da), interleukin (IL)-8 (8,000 Da), IL-6 (22,000 Da), and tumor necrosis factor (TNF)-α (51,000 Da). Quantity of test solution flow and filtration flow (QF) were set to 150 ml/min and 10, 20, and 35 ml/min, respectively. Clinical CVVH settings were blood flow (QB): 150 ml/min and QF: 35 ml/min. Samples were obtained from pre- and posthemofilters, and clearance of target substances was determined during pre- and postdilution CVVH in experimental and clinical conditions. Clearance changed according to QF during both pre- and postdilution CVVH in the experiment. Clearance of creatinine, inulin (experiment only), and IL-8 during postdilution CVVH was superior to that during predilution CVVH. Few differences were seen in clearance of IL-6 and TNF-α between dilution methods in the experiment and clinical practice. Clearance of IL-8 and IL-6 decreased during postdilution CVVH over 24 hr but did not change during predilution CVVH in clinical practice. Predilution CVVH is useful for stable cytokine clearance in septic patients with acute kidney injury.