The polymyxin-B direct hemoperfusion OPTimal Initiation timing with Catecholamine PMX-OPTIC study: A multicenter retrospective observational study

Kensuke Nakamura; Tetsuya Okazaki; Akihito Tampo; Katsunori Mochizuki; Naoki Kanda; Takahiro Ono; Kunio Yanagita; Taro Shimomura; Taichi Murase; Ken Saito; Takahiro Hirayama; Tomoaki Ito; Koji Ogawa; Mizuki Nakamura; Tomohiro Oda; Takeshi Morishima; Takuma Fukushima; Hiroharu Yasui; Naoki Akashi; Kojiro Oshima; Hiroo Kawarazaki; Tsukasa Akiba; Susumu Uemura; Yuhei Honma; Kenichi Nitta; Koji Okamoto; Shunsuke Takaki; Hirotaka Takeda; Chizuru Yamashita

doi:10.1111/aor.14865

The polymyxin-B direct hemoperfusion OPTimal Initiation timing with Catecholamine PMX-OPTIC study: A multicenter retrospective observational study

Artif Organs. 2024 Sep 18. doi: 10.1111/aor.14865. Online ahead of print.

Authors

Kensuke Nakamura^{1

2}, Tetsuya Okazaki³, Akihito Tampo⁴, Katsunori Mochizuki⁵, Naoki Kanda², Takahiro Ono⁶, Kunio Yanagita⁷, Taro Shimomura⁸, Taichi Murase⁹, Ken Saito¹⁰, Takahiro Hirayama¹¹, Tomoaki Ito¹², Koji Ogawa¹³, Mizuki Nakamura¹⁴, Tomohiro Oda¹⁵, Takeshi Morishima¹⁶, Takuma Fukushima¹⁷, Hiroharu Yasui¹⁸, Naoki Akashi², Kojiro Oshima¹⁹, Hiroo Kawarazaki²⁰, Tsukasa Akiba²¹, Susumu Uemura²², Yuhei Honma²³, Kenichi Nitta²⁴, Koji Okamoto²⁵, Shunsuke Takaki¹, Hirotaka Takeda²⁶, Chizuru Yamashita²⁷

Affiliations

¹ Department of Critical Care Medicine, Yokohama City University Hospital, Yokohama, Kanagawa, Japan.
² Department of Emergency and Critical Care Medicine, Hitachi General Hospital, Ibaraki, Japan.
³ Department of Clinical Engineering, Kyoto Okamoto Memorial Hospital, Kyoto, Japan.
⁴ Department of Emergency Medicine, Asahikawa Medical University, Asahikawa, Hokkaido, Japan.
⁵ Department of Emergency and Critical Care Medicine, Osaka Medical and Pharmaceutical University, Osaka, Japan.
⁶ Department of Emergency and Critical Care Medicine, University of Tsukuba Hospital, Ibaraki, Japan.
⁷ Department of Intensive Care Medicine, Tokyo Medical University Ibaraki Medical Center, Ibaraki, Japan.
⁸ Department of Clinical Engineering, Japanese Red Cross Osaka Hospital, Osaka, Japan.
⁹ Department of Clinical Engineering, Ijinkai Takeda General Hospital, Kyoto, Japan.
¹⁰ Department of Clinical Engineering, Medical Corporation Tokushukai, Uji Tokushukai Hospital, Kyoto, Japan.
¹¹ Department of Emergency, Critical Care and Disaster Medicine, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University, Okayama, Japan.
¹² Department of Clinical Engineering, Kokura Memorial Hospital, Fukuoka, Japan.
¹³ Department of Clinical Engineering, National Cerebral and Cardiovascular Center, Osaka, Japan.
¹⁴ Department of Clinical Engineering, Nara Prefecture Seiwa Medical Center, Nara, Japan.
¹⁵ Department of Clinical Engineering, Toyooka Public Hospital, Toyooka, Hyogo, Japan.
¹⁶ Department of Clinical Engineering, Akashi Medical Center, Akashi, Hyogo, Japan.
¹⁷ Department of Clinical Engineering, Fukuoka Wajiro Hospital, Fukuoka, Japan.
¹⁸ Department Medical Engineer Center, Matsue City Hospital, Matsue, Shimane, Japan.
¹⁹ Department Blood Purification, National Defence Medical College Hospital, Saitama, Japan.
²⁰ Department of the Fourth Internal Medicine, Teikyo University Mizonokuchi Hospital, Kawasaki, Kanagawa, Japan.
²¹ Department Clinical Engineering, Tsuchiura Kyodo General Hospital, Ibaraki, Japan.
²² Department of Clinical Engineering, Nikko Memorial Hospital, Muroran, Hokkaido, Japan.
²³ Division of Clinical Engineering, Asahikawa Medical University Hospital, Asahikawa, Hokkaido, Japan.
²⁴ Department of Emergency and Critical Care Medicine, Shinshu University School of Medicine, Nagano, Japan.
²⁵ Division of Nephrology, Rheumatology and Endocrinology, Tohoku University Graduate School of Medicine, Sendai, Miyagi, Japan.
²⁶ Department of Clinical Engineering, Nanpuh Hospital, Kagoshima, Japan.
²⁷ Department of Anesthesiology and Critical Care Medicine, Fujita Health University School of Medicine, Toyoake, Aichi, Japan.

PMID: 39291793
DOI: 10.1111/aor.14865

Abstract

Background: Polymyxin-B direct hemoperfusion (PMX-DHP) is an endotoxin adsorption column-based blood purification therapy. Since one of the most potent effects of PMX-DHP is blood pressure elevations, it may be the most effective when it is introduced at the time when the need for vasopressors is the greatest, which, in turn, may reduce mortality.

Methods: A multicenter retrospective study was conducted at 24 ICUs in Japan. In each ICU, the 20 most recent consecutive cases of septic shock treated with PMX-DHP were analyzed. The duration between the time of the peak vasopressive agent dose, expressed as the noradrenaline equivalent dose (NEq), and the time of PMX initiation was evaluated. The primary outcome was 28-day mortality, and a multivariable analysis was performed to investigate factors associated with mortality.

Results: A total of 480 septic shock patients were included in the analysis. Among all patients, the 28-day mortality group was older, more severely ill, and had a higher body mass index. The NEq peak and NEq on PMX-DHP initiation were both higher in deceased patients. Regarding the timing of PMX-DHP initiation from the NEq peak, -4 << 4 h had more survivors (229/304, 75.3%) than ≤-4 h (50/75, 66.7%) and ≥4 h (66/101, 65.4%) (p = 0.085). When -4 << 4 h was assigned as a reference, the timing of PMX-DHP initiation from the NEq peak of ≤-4 h had an odds ratio of 1.96 (1.07-3.58), p = 0.029, while ≥4 h had an odds ratio of 1.64 (0.94-2.87), p = 0.082 for 28-day mortality, in the multivariable regression analysis. A spline curve of the relationship between the probability of death and the timing of PMX-DHP initiation from the NEq peak showed a downward convex curve with a nadir at timing = 0. The odds ratios of the timing of PMX-DHP initiation other than -4 << 4 h were significantly higher in an older age, male sex, lower BMI, more severe illness, and higher oxygenation.

Conclusions: The induction of PMX-DHP at the time of the peak vasopressor dose correlated with lower mortality. PMX-DHP is one of the options available for elevating blood pressure in septic shock, and its initiation either too early or late for shock peak may not improve the outcome.

Keywords: PMX‐DHP; blood purification; catecholamine; hemo‐absorption; sepsis.