Abstract: FR-PO100

Therapeutic Plasma Exchange as Rescue Therapy in Refractory Septic Shock

Session Information

Category: Acute Kidney Injury

  • 003 AKI: Clinical and Translational

Authors

  • David, Sascha, Medizinische Hoschschule Hannover, Hannover, Germany
  • Haller, Hermann G., Hannover Medical School, Hannover, Germany
  • Schmidt, Bernhard M.W., Hannover Medical School, Hannover, Germany
  • Kielstein, Jan T., Academic Teaching Hospital Braunschweig, Braunschweig, Germany
Background

Sepsis is a life-threatening dysregulated host response to infection. Given the injurious role of 1) the overwhelming immune response and 2) the consumption of protective plasmatic factors (vWF cleaving proteases etc.) we hypothesize that early therapeutic plasma exchange (TPE) in severely ill individuals might be beneficial. TPE combines 2 aspects in 1 procedure: Removal of harmful circulating molecules and replacement of protective plasma proteins.

Methods

We have included 14 septic shock patients (onset < 12 h) requiring high doses of noradrenaline (> 0.4 ug/kg/min). TPE (against FFP) was performed within 4 hrs. Clinical and chemical data were obtained longitudinally besides the evaluation of 28-day mortality. Plasma samples before and after TPE were obtained for stimulation of human umbilical vein endothelial cells (HUVECs) to analyze their phenotype with regard to permeability in vitro (fluorescent immunocytochemistry & transendothelial electrical resistance (TER)).

Results

The 28-day mortality in this study was found 20% lower (69.2%) as the predicted mortality (88.95%) by APACHE II score (37.6±4). TPE resulted in hemodynamic stabilization as indicated by mean arterial pressure (63±11 vs. 70±9 mmHg, p=0.002) and lower vasopressor requirement (NA 0.93±0.5 vs. 0.6±0.3 ug/kg/min, p<0.001). Fluid balance was also positively affected probably by reduced capillary leakage. This is supported by ex vivo stimulation of HUVECs with septic plasma where plasma before TPE induced severe alteration of cellular architecture including a disassembly of adherens junction (VE-cadherin IF) and a dramatic increase in permeability (TER, Figure). The same patients’ plasma after TPE did not induce this typical septic phenotype.

Conclusion

This pilot study supports our hypothesis that early TPE in highly unstable patients might be beneficial with regard to hemodynamic stability, microcirculatory perfusion and overall outcome. A multicenter randomized trial powered for mortality is highly desirable.