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Clinical and biochemical endpoints and predictors of response to plasma exchange in septic shock: results from a randomized controlled trial

Stahl, Klaus; Wand, Philipp; Seeliger, Benjamin; Wendel-Garcia, Pedro D; Schmidt, Julius; Schmidt, Bernhard M W; Sauer, Andrea; Lehmann, Felix; Budde, Ulrich; Busch, Markus; Wiesner, Olaf; Welte, Tobias; Haller, Hermann; Wedemeyer, Heiner; Putensen, Christian; Hoeper, Marius M; Bode, Christian; David, Sascha (2022). Clinical and biochemical endpoints and predictors of response to plasma exchange in septic shock: results from a randomized controlled trial. Critical Care, 26:134.

Abstract

Background
Recently, a randomized controlled trial (RCT) demonstrated rapid but individually variable hemodynamic improvement with therapeutic plasma exchange (TPE) in patients with septic shock. Prediction of clinical efficacy in specific sepsis treatments is fundamental for individualized sepsis therapy.

Methods
In the original RCT, patients with septic shock of < 24 h duration and norepinephrine (NE) requirement ≥ 0.4 μg/kg/min received standard of care (SOC) or SOC + one single TPE. Here, we report all clinical and biological endpoints of this study. Multivariate mixed-effects modeling of NE reduction was performed to investigate characteristics that could be associated with clinical response to TPE.

Results
A continuous effect of TPE on the reduction in NE doses over the initial 24 h was observed (SOC group: estimated NE dose reduction of 0.005 µg/kg/min per hour; TPE group: 0.018 µg/kg/min per hour, p = 0.004). Similarly, under TPE, serum lactate levels, continuously decreased over the initial 24 h in the TPE group, whereas lactate levels increased under SOC (p = 0.001). A reduction in biomarkers and disease mediators (such as PCT (p = 0.037), vWF:Ag (p < 0.001), Angpt-2 (p = 0.009), sTie-2 (p = 0.005)) along with a repletion of exhausted protective factors (such as AT-III (p = 0.026), Protein C (p = 0.012), ADAMTS-13 (p = 0.008)) could be observed in the TPE but not in the SOC group. In a multivariate mixed effects model, increasing baseline lactate levels led to greater NE dose reduction effects with TPE as opposed to SOC (p = 0.004).

Conclusions
Adjunctive TPE is associated with the removal of injurious mediators and repletion of consumed protective factors altogether leading to preserved hemodynamic stabilization in refractory septic shock. We identified that baseline lactate concentration as a potential response predictor might guide future designing of large RCTs that will further evaluate TPE with regard to hard endpoints.

Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > University Hospital Zurich > Institute of Intensive Care Medicine
Dewey Decimal Classification:610 Medicine & health
Language:English
Date:12 May 2022
Deposited On:17 May 2022 14:51
Last Modified:27 Oct 2024 02:40
Publisher:BioMed Central
ISSN:1364-8535
OA Status:Gold
Free access at:PubMed ID. An embargo period may apply.
Publisher DOI:https://doi.org/10.1186/s13054-022-04003-2
PubMed ID:35551628
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  • Licence: Creative Commons: Attribution 4.0 International (CC BY 4.0)

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