Therapeutic Rationale for Endotoxin Removal with Polymyxin B Immobilized Fiber Column (PMX) for Septic Shock



Conclusion

PMX-HP has been safely used for the treatment of septic shock since 1994. The survival benefit of this therapy is still suggestive by the cohort study using a large clinical database. A currently ongoing TIGRIS multicenter randomized controlled trial is expected to prove the evidence for the treatment of septic shock patients with endotoxemia who are likely to benefit from PMX-HP. PMX-HP is not only endotoxin removal, but also an immunomodulatory device. Further study is required to clarify the mechanism of action of PMX-HP and to apply for a good patient population.

Feb 2021.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7926968/

From the same article, I like this too ...

Novelli et al. investigated the usefulness of EAA for patients after surge. Thirty-eight post-surgical patients were enrolled. Seventeen patients with a high level of EA value (≥0.6) received standard therapy plus PMX-HP every 24 h to lower the EA value to less than 0.4. Seven patients required two sessions of PMX-HP, eight required three sessions, and two required four sessions. The EA value steadily decreased following PMX-HP application. As a result, all 17 patients survived for 28 days. These studies demonstrated that the blood endotoxin level could be reduced with PMX-HP. In the case that the level does not decrease by one session, the repeated application might be effective depending on the endotoxin burden of the patient.


A dosing problem?

Note also the suggestion that Euphrates trial results may have been hurt by including patiients with EAA levels >.9 (burden to high for filter to be effective)

When EA values are greater than 0.9, endotoxin mass concentrations can be much greater than 4 ng/mL. This means that in a total whole blood volume of 5 L with endotoxin equally distributed between cells and plasma, a total blood load greater than 20 μg could be achieved. If endotoxin is distributed additionally into the extracellular space (10 L), then the total extracellular endotoxin load could be significantly higher than the adsorption capacity of a single PMX-HP. In the dose–response curve of endotoxin burden (LPS in ng/mL, y axis) and EA value (x axis), it was shown that above an EA value of 0.9 (corresponding to >4 ng/mL of LPS) the curve exhibits an asymptotic behavior and thus cannot be used to quantitate LPS levels in this range. The patients with an EA value more than 0.9 may have high burden of endotoxin and may not be adequate to enroll in the current EUPHRATES protocol. Post hoc analysis gave the hypothesis-generating results. The TIGRIS multicenter randomized controlled trial in the US is ongoing to prove this hypothesis.


And a reminder about Euphas. Historically important.

The EUPHAS study in Italy was the first multicenter randomized controlled study with PMX-HP  The targeted population was severe sepsis and/or septic shock patients who underwent emergency surgery for intra-abdominal Gram-negative infections. PMX-HP added to conventional therapy significantly improved mean arterial pressure and vasopressor requirement and reduced 28-day mortality by 32% (11/34 patients) in the PMX-HP group and 53% (16/30 patients) in the conventional therapy group. However, the number of the enrolled patients was small, and the study was terminated early because of a statistically significant reduction of mortality in PMX-HP group. It was declared unethical to deprive a potentially beneficial therapy to a group of patients that carry high mortality rates. This invited some criticism and failed to give a definitive answer.

MM