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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. [ABSTRACT FROM AUTHOR] more...

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)], PaO/FiO 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. PaO/FiO 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. [ABSTRACT FROM AUTHOR] more...

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, PaO/FiO, 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 PaO/FiO 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. [ABSTRACT FROM AUTHOR] more...