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. 2025 May 9;29(1):187.
doi: 10.1186/s13054-025-05422-7.

Time to administer polymyxin B hemoperfusion and hemodynamics in patients with septic shock requiring high-dose norepinephrine: a predetermined analysis of a prospective cohort study

Kyohei Miyamoto  1 , Yu Kawazoe  2 , Noriko Miyagawa  2 , Hitoshi Yamamura  3 , Yoshinori Ohta  4 , Takuya Kimura  5 , Yukitoshi Toyoda  6 , Michihito Kyo  7   8 , Tetsuya Sato  9 , Masashi Kinjo  10 , Masaki Takahashi  11 , Junichi Maruyama  12 , Hiroshi Matsuura  13 , Kazunori Fukushima  14 , Satoru Murata  15 , Tomoya Okazaki  16 , Tsuyoshi Suzuki  17 , Toshihiro Sakurai  18 , Gaku Takahashi  19 , Tasuku Hanajima  20 , Takeshi Morimoto  21
Affiliations

Time to administer polymyxin B hemoperfusion and hemodynamics in patients with septic shock requiring high-dose norepinephrine: a predetermined analysis of a prospective cohort study

Kyohei Miyamoto et al. Crit Care. .

Abstract

Background: Delayed administration of polymyxin B hemoperfusion (PMX-HP) for septic shock could diminish its efficacy in real-world clinical settings.

Methods: BEAT-SHOCK (BEst Available Treatment for septic SHOCK) registry is a prospective registry consisting of 309 adult patients with septic shock requiring high-dose norepinephrine (≥ 0.2 μg/kg/min). This predetermined analysis included 82 patients treated with PMX-HP. They were grouped according to the median time from intensive care unit (ICU) admission to administration of PMX-HP: the early administration group (n = 40) and the late administration group (n = 42). The primary outcome was short-term hemodynamic status, including mean arterial pressure and vasoactive-inotropic score (VIS; calculated from doses of dopamine, dobutamine, norepinephrine, epinephrine, vasopressin, milrinone, and levosimendan) within 48 h after ICU admission.

Results: The median time from ICU admission to administration of PMX-HP was 265 min (interquartile range [IQR]: 113-480). The median ages were 70 (IQR: 59-81) and 72 (IQR: 64-80) years (P = 0.77), and 21/40 (53%) and 25/42 (60%) patients were male (P = 0.52) in the early and late administration groups, respectively. The dose of norepinephrine at ICU admission was 0.33 (IQR: 0.24-0.47) and 0.30 (IQR: 0.22-0.34) μg/kg/min in the early and late administration groups, respectively (P = 0.17). Within 48 h after ICU admission, mean arterial pressure was significantly higher at 6 h and 8 h, and VIS was significantly lower at 8 h and thereafter in the early administration group. Within a 28-day period, there were 23 (IQR: 21-25) and 21 (IQR: 0-24) vasopressor/inotrope-free days (P = 0.027), and 18 (IQR: 1-23) and 14 (IQR: 0-19) ICU-free days (P = 0.025) in the early and late administration groups, respectively. The cumulative mortality at 90 days was 15.3% in the early administration group and 31.3% in the late administration group (adjusted hazard ratio 0.38; 95% confidence interval 0.13-1.09).

Conclusions: In patients with septic shock, early administration of PMX-HP was associated with higher mean arterial pressure and lower VIS within 48 h after ICU admission. Additionally, it may be associated with an improved clinical course, represented by more ICU-free and vasopressor/inotrope-free days. Trial registration UMIN Clinical Trial Registry on 1 November 2019 (registration no. UMIN000038302).

Keywords: Blood purification; Polymyxin B hemoperfusion; Septic shock.

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Conflict of interest statement

Declarations. Ethical approval and consent to participate: The ethics committee of Tohoku University Hospital (Approval Number 2019-1-402) and the ethics committees of all other participating hospitals approved this study with an opt-out policy in accordance with the Ethical Guidelines for Medical and Biological Research Involving Human Subjects. Written informed consent was obtained from patients or their proxies to collect data about functional outcomes at 90 days by distributing questionnaires. This study was conducted in compliance with the Ethical Guidelines for Medical and Biological Research Involving Human Subjects and the principles of the Declaration of Helsinki. Consent for publication: The ethics committee of Tohoku University Hospital (approval number 2019-1-402) and the ethics committees of all other participating hospitals approved this study with an opt-out policy. Competing interests: Dr. Miyamoto reports lecturer's fees from Asahi Kasei Pharma, Japan Blood Products Organization, and Chugai Pharmaceutical. Dr. Kawazoe reports lecturer’s fees from Toray Industries Inc. and Asahi Kasei Pharma. Dr. Kyo reports lecturer's fee from TXP Medical. Dr. Masaki Takahashi reports lecture's fees from Japan Blood Products Organization and Eisai Co., Ltd.. Dr. Gaku Takahashi reports lecturer’s fees from Toray Industries Inc. and Asahi Kasei Pharma. and JB Pharma. Dr. Hanajima reports lecturer's fee from Toray Industries Inc.. Dr Morimoto reports lecturer's fees from Abbott, AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, Daiichi Sankyo, Japan Lifeline, Pfizer, Tsumura and UCB; manuscript fee from Pfizer; advisory board for GlaxoSmithKline, Novartis and Teijin.

Figures

Fig. 1
Fig. 1
Patient flowchart. BEAT-SHOCK BEst Available Treatment for septic SHOCK, ICU intensive care units, NYHA New York Heart Association classification for heart failure, PMX-HP Polymyxin B hemoperfusion
Fig. 2
Fig. 2
Mean arterial pressure between early and late administration groups within 48 h after ICU admission. At 6 h and 8 h after ICU admission, mean arterial pressures were significantly higher in the early administration group. We used Wilcoxon rank sum test for each comparison between the early and late administration groups and the median values for mean arterial pressure are shown. ICU intensive care unit
Fig. 3
Fig. 3
Vasoactive-inotropic score between the early and late administration groups within 48 h after ICU admission. At 8 h and thereafter from ICU admission, vasoactive-inotropic score was significantly lower in the early administration group. Wilcoxon rank sum test was used for each comparison between the early and late administration groups. Figure shows the median values for vasoactive-inotropic score. ICU intensive care unit
Fig. 4
Fig. 4
Ninety-day mortality after ICU admission in the early and late administration groups. Time-to-event curve for death at 90 days after ICU admission is shown. The hazard ratio is from unadjusted and adjusted analyses by Cox proportional hazard model. In the adjusted model, we used predefined adjusters as age (≥ 65 years old), chronic illness (Charlson comorbidity index ≥ 3), disability (performance status ≥ 3), illness severity (acute physiology and chronic health evaluation II score ≥ 21), source of infection (urinary tract/abdomen or not), emergent surgery (yes/no), serum lactate concentration (≥ 4 mmol/L), vasoactive-inotropic score (≥ 30), and bacteremia (yes/no)
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