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Clinical impact of enhanced cytokine clearance with sustained high-efficiency daily diafiltration using a mediator-adsorbing membrane (SHEDD-fA) in patients with severe sepsis

Introduction

SHEDD-fA is an effective modality that makes the best use of three principles in the treatment of severe sepsis: diffusion, convection and adsorption. We reported the efficacy of SHEDD-fA for the treatment of severe sepsis at the 31st ISICEM 2011 [1]. Here we present the blood clearance (CL) of seven important cytokines with SHEDD-fA.

Methods

Ten critically ill patients were studied who were on SHEDD-fA, at QB = 150 ml/minute, QF = 1,500 ml/hour (post dilution) and QD = 300 to 500 ml/minute as a nonrenal indication. In order to maximize cytokine adsorption efficiency, we used a large-size (2.1 m2) PMMA dialyzer. Blood samples were taken to measure the CL of plasma cytokines (HMGB-1, IL-6, IL-8, IL-10, G-CSF, MCP-1 and MIP-1) at 1 hour and 3 hours after initiation (in one cytokine by 62 to 107 samples).

Results

The median values of CL with interquartile ranges of each cytokine (molecular weight: kDa) were: HMGB1 (30 kDa), 53.1 ml/minute (2.1 to 12.5); IL-6 (21 kDa), 39.9 ml/minute (12.4 to 70.6); IL-8 (8 kDa), 64.1 ml/minute (-0.5 to 82.0); IL-10 ml/minute (35 to 40 kDa), 45.6 ml/minute (0.5 to 88.3); G-CSF (19 kDa), 33.2 ml/minute (9.3 to 60.8); MCP-1 (8.7 kDa), 68.5 ml/minute (-14.4 to 125.4); and MIP-1 (7.8 kDa), 66.5 ml/minute (18.6 to 100.0). In particular, CL of HMGB1 was positively correlated with pre-SHEDD-fA blood levels, indicating the mechanism of HMGB1 removal was through adsorption. As a result of enhancing the intensity of the dosage, CL (53 ml/minute) of HMGB1 was higher than that (25 ml/minute) of an in vitro experiment that we reported at the 31st ISICEM 2011. See Figure 1.

Figure 1
figure 1

Correlation between clearance and blood level of cytokines.

Conclusion

Taking into account the fact that the creatinine CL of native kidney function is 100 ml/minute, our findings suggest that SHEDD-fA is a feasible adjusted modality for the treatment of patients with severe sepsis, with or without acute kidney injury. Considering our other laboratory findings, deep filtration may enhance blood clearance.

References

  1. Nishida O, et al.: Contrib Nephrol. 2011, 173: 172-181.

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Nishida, O., Nakamura, T., Kuriyama, N. et al. Clinical impact of enhanced cytokine clearance with sustained high-efficiency daily diafiltration using a mediator-adsorbing membrane (SHEDD-fA) in patients with severe sepsis. Crit Care 16 (Suppl 1), P383 (2012). https://doi.org/10.1186/cc10990

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