The polymyxin-B direct hemoperfusion OPTimal Initiation timing with Catecholamine PMX-OPTIC study: A multicenter retrospective observational study
Corresponding Author
Kensuke Nakamura
Department of Critical Care Medicine, Yokohama City University Hospital, Yokohama, Kanagawa, Japan
Department of Emergency and Critical Care Medicine, Hitachi General Hospital, Ibaraki, Japan
Correspondence
Kensuke Nakamura, Department Critical Care Medicine, Yokohama City University Hospital, 3-9 Fukuura, Kanazawa-ku, Yokohama 236-0004, Kanagawa, Japan.
Email: [email protected]
Search for more papers by this authorTetsuya Okazaki
Department of Clinical Engineering, Kyoto Okamoto Memorial Hospital, Kyoto, Japan
Search for more papers by this authorAkihito Tampo
Department of Emergency Medicine, Asahikawa Medical University, Asahikawa, Hokkaido, Japan
Search for more papers by this authorKatsunori Mochizuki
Department of Emergency and Critical Care Medicine, Osaka Medical and Pharmaceutical University, Osaka, Japan
Search for more papers by this authorNaoki Kanda
Department of Emergency and Critical Care Medicine, Hitachi General Hospital, Ibaraki, Japan
Search for more papers by this authorTakahiro Ono
Department of Emergency and Critical Care Medicine, University of Tsukuba Hospital, Ibaraki, Japan
Search for more papers by this authorKunio Yanagita
Department of Intensive Care Medicine, Tokyo Medical University Ibaraki Medical Center, Ibaraki, Japan
Search for more papers by this authorTaro Shimomura
Department of Clinical Engineering, Japanese Red Cross Osaka Hospital, Osaka, Japan
Search for more papers by this authorTaichi Murase
Department of Clinical Engineering, Ijinkai Takeda General Hospital, Kyoto, Japan
Search for more papers by this authorKen Saito
Department of Clinical Engineering, Medical Corporation Tokushukai, Uji Tokushukai Hospital, Kyoto, Japan
Search for more papers by this authorTakahiro Hirayama
Department of Emergency, Critical Care and Disaster Medicine, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University, Okayama, Japan
Search for more papers by this authorTomoaki Ito
Department of Clinical Engineering, Kokura Memorial Hospital, Fukuoka, Japan
Search for more papers by this authorKoji Ogawa
Department of Clinical Engineering, National Cerebral and Cardiovascular Center, Osaka, Japan
Search for more papers by this authorMizuki Nakamura
Department of Clinical Engineering, Nara Prefecture Seiwa Medical Center, Nara, Japan
Search for more papers by this authorTomohiro Oda
Department of Clinical Engineering, Toyooka Public Hospital, Toyooka, Hyogo, Japan
Search for more papers by this authorTakeshi Morishima
Department of Clinical Engineering, Akashi Medical Center, Akashi, Hyogo, Japan
Search for more papers by this authorTakuma Fukushima
Department of Clinical Engineering, Fukuoka Wajiro Hospital, Fukuoka, Japan
Search for more papers by this authorHiroharu Yasui
Department Medical Engineer Center, Matsue City Hospital, Matsue, Shimane, Japan
Search for more papers by this authorNaoki Akashi
Department of Emergency and Critical Care Medicine, Hitachi General Hospital, Ibaraki, Japan
Search for more papers by this authorKojiro Oshima
Department Blood Purification, National Defence Medical College Hospital, Saitama, Japan
Search for more papers by this authorHiroo Kawarazaki
Department of the Fourth Internal Medicine, Teikyo University Mizonokuchi Hospital, Kawasaki, Kanagawa, Japan
Search for more papers by this authorTsukasa Akiba
Department Clinical Engineering, Tsuchiura Kyodo General Hospital, Ibaraki, Japan
Search for more papers by this authorSusumu Uemura
Department of Clinical Engineering, Nikko Memorial Hospital, Muroran, Hokkaido, Japan
Search for more papers by this authorYuhei Honma
Division of Clinical Engineering, Asahikawa Medical University Hospital, Asahikawa, Hokkaido, Japan
Search for more papers by this authorKenichi Nitta
Department of Emergency and Critical Care Medicine, Shinshu University School of Medicine, Nagano, Japan
Search for more papers by this authorKoji Okamoto
Division of Nephrology, Rheumatology and Endocrinology, Tohoku University Graduate School of Medicine, Sendai, Miyagi, Japan
Search for more papers by this authorShunsuke Takaki
Department of Critical Care Medicine, Yokohama City University Hospital, Yokohama, Kanagawa, Japan
Search for more papers by this authorHirotaka Takeda
Department of Clinical Engineering, Nanpuh Hospital, Kagoshima, Japan
Search for more papers by this authorChizuru Yamashita
Department of Anesthesiology and Critical Care Medicine, Fujita Health University School of Medicine, Toyoake, Aichi, Japan
Search for more papers by this authorCorresponding Author
Kensuke Nakamura
Department of Critical Care Medicine, Yokohama City University Hospital, Yokohama, Kanagawa, Japan
Department of Emergency and Critical Care Medicine, Hitachi General Hospital, Ibaraki, Japan
Correspondence
Kensuke Nakamura, Department Critical Care Medicine, Yokohama City University Hospital, 3-9 Fukuura, Kanazawa-ku, Yokohama 236-0004, Kanagawa, Japan.
Email: [email protected]
Search for more papers by this authorTetsuya Okazaki
Department of Clinical Engineering, Kyoto Okamoto Memorial Hospital, Kyoto, Japan
Search for more papers by this authorAkihito Tampo
Department of Emergency Medicine, Asahikawa Medical University, Asahikawa, Hokkaido, Japan
Search for more papers by this authorKatsunori Mochizuki
Department of Emergency and Critical Care Medicine, Osaka Medical and Pharmaceutical University, Osaka, Japan
Search for more papers by this authorNaoki Kanda
Department of Emergency and Critical Care Medicine, Hitachi General Hospital, Ibaraki, Japan
Search for more papers by this authorTakahiro Ono
Department of Emergency and Critical Care Medicine, University of Tsukuba Hospital, Ibaraki, Japan
Search for more papers by this authorKunio Yanagita
Department of Intensive Care Medicine, Tokyo Medical University Ibaraki Medical Center, Ibaraki, Japan
Search for more papers by this authorTaro Shimomura
Department of Clinical Engineering, Japanese Red Cross Osaka Hospital, Osaka, Japan
Search for more papers by this authorTaichi Murase
Department of Clinical Engineering, Ijinkai Takeda General Hospital, Kyoto, Japan
Search for more papers by this authorKen Saito
Department of Clinical Engineering, Medical Corporation Tokushukai, Uji Tokushukai Hospital, Kyoto, Japan
Search for more papers by this authorTakahiro Hirayama
Department of Emergency, Critical Care and Disaster Medicine, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University, Okayama, Japan
Search for more papers by this authorTomoaki Ito
Department of Clinical Engineering, Kokura Memorial Hospital, Fukuoka, Japan
Search for more papers by this authorKoji Ogawa
Department of Clinical Engineering, National Cerebral and Cardiovascular Center, Osaka, Japan
Search for more papers by this authorMizuki Nakamura
Department of Clinical Engineering, Nara Prefecture Seiwa Medical Center, Nara, Japan
Search for more papers by this authorTomohiro Oda
Department of Clinical Engineering, Toyooka Public Hospital, Toyooka, Hyogo, Japan
Search for more papers by this authorTakeshi Morishima
Department of Clinical Engineering, Akashi Medical Center, Akashi, Hyogo, Japan
Search for more papers by this authorTakuma Fukushima
Department of Clinical Engineering, Fukuoka Wajiro Hospital, Fukuoka, Japan
Search for more papers by this authorHiroharu Yasui
Department Medical Engineer Center, Matsue City Hospital, Matsue, Shimane, Japan
Search for more papers by this authorNaoki Akashi
Department of Emergency and Critical Care Medicine, Hitachi General Hospital, Ibaraki, Japan
Search for more papers by this authorKojiro Oshima
Department Blood Purification, National Defence Medical College Hospital, Saitama, Japan
Search for more papers by this authorHiroo Kawarazaki
Department of the Fourth Internal Medicine, Teikyo University Mizonokuchi Hospital, Kawasaki, Kanagawa, Japan
Search for more papers by this authorTsukasa Akiba
Department Clinical Engineering, Tsuchiura Kyodo General Hospital, Ibaraki, Japan
Search for more papers by this authorSusumu Uemura
Department of Clinical Engineering, Nikko Memorial Hospital, Muroran, Hokkaido, Japan
Search for more papers by this authorYuhei Honma
Division of Clinical Engineering, Asahikawa Medical University Hospital, Asahikawa, Hokkaido, Japan
Search for more papers by this authorKenichi Nitta
Department of Emergency and Critical Care Medicine, Shinshu University School of Medicine, Nagano, Japan
Search for more papers by this authorKoji Okamoto
Division of Nephrology, Rheumatology and Endocrinology, Tohoku University Graduate School of Medicine, Sendai, Miyagi, Japan
Search for more papers by this authorShunsuke Takaki
Department of Critical Care Medicine, Yokohama City University Hospital, Yokohama, Kanagawa, Japan
Search for more papers by this authorHirotaka Takeda
Department of Clinical Engineering, Nanpuh Hospital, Kagoshima, Japan
Search for more papers by this authorChizuru Yamashita
Department of Anesthesiology and Critical Care Medicine, Fujita Health University School of Medicine, Toyoake, Aichi, Japan
Search for more papers by this authorAbstract
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.
CONFLICT OF INTEREST STATEMENT
We declare that we have no conflicts of interest related to this study.
Open Research
DATA AVAILABILITY STATEMENT
Individual participant data that underlie the results reported in the present study are available from the corresponding author upon reasonable request.
Supporting Information
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| aor14865-sup-0001-AppendixS1.docxWord 2007 document , 41.5 KB |
Table S1. |
Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
REFERENCES
- 1Shoji H. Extracorporeal endotoxin removal for the treatment of sepsis: endotoxin adsorption cartridge (Toraymyxin). Ther Apher Dial. 2003; 7(1): 108–114. https://doi.org/10.1046/j.1526-0968.2003.00005.x
- 2Payen DM, Guilhot J, Launey Y, Lukaszewicz AC, Kaaki M, Veber B, et al. Early use of polymyxin B hemoperfusion in patients with septic shock due to peritonitis: a multicenter randomized control trial. Intensive Care Med. 2015; 41(6): 975–984. https://doi.org/10.1007/s00134-015-3751-z
- 3Dellinger RP, Bagshaw SM, Antonelli M, Foster DM, Klein DJ, Marshall JC, et al. Effect of targeted polymyxin B hemoperfusion on 28-day mortality in patients with septic shock and elevated endotoxin level: the EUPHRATES randomized clinical trial. JAMA. 2018; 320(14): 1455–1463. https://doi.org/10.1001/jama.2018.14618
- 4Klein DJ, Foster D, Walker PM, Bagshaw SM, Mekonnen H, Antonelli M. Polymyxin B hemoperfusion in endotoxemic septic shock patients without extreme endotoxemia: a post hoc analysis of the EUPHRATES trial. Intensive Care Med. 2018; 44(12): 2205–2212. https://doi.org/10.1007/s00134-018-5463-7
- 5Osawa I, Goto T, Kudo D, Hayakawa M, Yamakawa K, Kushimoto S, et al. Targeted therapy using polymyxin B hemadsorption in patients with sepsis: a post-hoc analysis of the JSEPTIC-DIC study and the EUPHRATES trial. Crit Care. 2023; 27(1): 245. https://doi.org/10.1186/s13054-023-04533-3
- 6Cruz DN, Perazella MA, Bellomo R, de Cal M, Polanco N, Corradi V, et al. Effectiveness of polymyxin B-immobilized fiber column in sepsis: a systematic review. Crit Care. 2007; 11(2): R47. https://doi.org/10.1186/cc5780
- 7Rivers E, Nguyen B, Havstad S, Ressler J, Muzzin A, Knoblich B, et al. Early goal-directed therapy in the treatment of severe sepsis and septic shock. N Engl J Med. 2001; 345(19): 1368–1377. https://doi.org/10.1056/NEJMoa010307
- 8Nakamura K, Doi K, Inokuchi R, Fukuda T, Hiruma T, Ishii T, et al. Endotoxin adsorption by polymyxin B column or intraaortic balloon pumping use for severe septic cardiomyopathy. Am J Emerg Med. 2013; 31(5): 893.e1–893.e3. https://doi.org/10.1016/j.ajem.2012.12.042
- 9Sekino M, Murakami Y, Sato S, Shintani R, Kaneko S, Iwasaki N, et al. Modifications of peripheral perfusion in patients with vasopressor-dependent septic shock treated with polymyxin B-direct hemoperfusion. Sci Rep. 2023; 13(1): 7295. https://doi.org/10.1038/s41598-023-34084-0
- 10Russell JA. Vasopressor therapy in critically ill patients with shock. Intensive Care Med. 2019; 45(11): 1503–1517. https://doi.org/10.1007/s00134-019-05801-z
- 11Dünser MW, Ruokonen E, Pettilä V, Ulmer H, Torgersen C, Schmittinger CA, et al. Association of arterial blood pressure and vasopressor load with septic shock mortality: a post hoc analysis of a multicenter trial. Crit Care. 2009; 13(6): R181. https://doi.org/10.1186/cc8167
- 12Chihara S, Masuda Y, Tatsumi H, Nakano K, Shimada T, Murohashi T, et al. Early induction of direct hemoperfusion with a polymyxin-B immobilized column is associated with amelioration of hemodynamic derangement and mortality in patients with septic shock. J Artif Organs. 2017; 20(1): 71–75. https://doi.org/10.1007/s10047-016-0922-9
- 13Tanaka T, Tabata T, Fujino K, Tsujita Y, Eguchi Y. Impact of timing of polymyxin B-immobilized fiber column direct hemoperfusion on outcome in patients with septic shock: a single-center observational study. Acute Med Surg. 2020; 7(1):e446. https://doi.org/10.1002/ams2.446
- 14Bone RC. Toward a theory regarding the pathogenesis of the systemic inflammatory response syndrome: what we do and do not know about cytokine regulation. Crit Care Med. 1996; 24(1): 163–172. https://doi.org/10.1097/00003246-199601000-00026
- 15Seymour CW, Liu VX, Iwashyna TJ, Brunkhorst FM, Rea TD, Scherag A, et al. Assessment of clinical criteria for sepsis: for the third international consensus definitions for sepsis and septic shock (Sepsis-3). JAMA. 2016; 315(8): 762–774. https://doi.org/10.1001/jama.2016.0288
- 16Fujinaga J, Otake T, Umeda T, Fukuoka T. Case volume and specialization in critically ill emergency patients: a nationwide cohort study in Japanese ICUs. J Intensive Care. 2024; 12(1): 20. https://doi.org/10.1186/s40560-024-00733-3
- 17Khanna A, English SW, Wang XS, Ham K, Tumlin J, Szerlip H, et al. Angiotensin II for the treatment of vasodilatory shock. N Engl J Med. 2017; 377(5): 419–430. https://doi.org/10.1056/NEJMoa1704154
- 18Nishibori M, Takahashi HK, Katayama H, Mori S, Saito S, Iwagaki H, et al. Specific removal of monocytes from peripheral blood of septic patients by polymyxin B-immobilized filter column. Acta Med Okayama. 2009; 63(1): 65–69. https://doi.org/10.18926/AMO/31855
- 19Abe S, Seo Y, Hayashi H, Matsuda K, Usuki J, Azuma A, et al. Neutrophil adsorption by polymyxin B-immobilized fiber column for acute exacerbation in patients with interstitial pneumonia: a pilot study. Blood Purif. 2010; 29(4): 321–326. https://doi.org/10.1159/000287232
- 20Gocho T, Mori H, Islam MM, Maruchi Y, Takenaka N, Tomino A, et al. Removal of circulating neutrophil extracellular trap components with an immobilized polymyxin B filter: a preliminary study. Shock. 2020; 54(1): 44–49. https://doi.org/10.1097/SHK.0000000000001476
- 21Wang Y, Liu Y, Sarker KP, Nakashima M, Serizawa T, Kishida A, et al. Polymyxin B binds to anandamide and inhibits its cytotoxic effect. FEBS Lett. 2000; 470(2): 151–155. https://doi.org/10.1016/s0014-5793(00)01313-2
- 22Kohro S, Imaizumi H, Yamakage M, Masuda Y, Namiki A, Asai Y, et al. Anandamide absorption by direct hemoperfusion with polymixin B-immobilized fiber improves the prognosis and organ failure assessment score in patients with sepsis. J Anesth. 2006; 20(1): 11–16. https://doi.org/10.1007/s00540-005-0366-5
- 23Ueno T, Ikeda T, Yokoyama T, Kihara Y, Konno O, Nakamura Y, et al. Reduction in circulating level of HMGB-1 following continuous renal replacement therapy in sepsis. Cytokine. 2016; 83: 206–209. https://doi.org/10.1016/j.cyto.2016.05.004
- 24Abe S, Hayashi H, Seo Y, Matsuda K, Kamio K, Saito Y, et al. Reduction in serum high mobility group box-1 level by polymyxin B-immobilized fiber column in patients with idiopathic pulmonary fibrosis with acute exacerbation. Blood Purif. 2011; 32(4): 310–316. https://doi.org/10.1159/000330325
- 25Seemann A, Boissier F, Razazi K, Carteaux G, de Prost N, Brun-Buisson C, et al. New-onset supraventricular arrhythmia during septic shock: prevalence, risk factors and prognosis. Ann Intensive Care. 2015; 5(1): 27. https://doi.org/10.1186/s13613-015-0069-5
- 26Suzuki T, Suzuki Y, Okuda J, Kurazumi T, Suhara T, Ueda T, et al. Sepsis-induced cardiac dysfunction and β-adrenergic blockade therapy for sepsis. J Intensive Care. 2017; 5: 22. https://doi.org/10.1186/s40560-017-0215-2
- 27Domizi R, Calcinaro S, Harris S, Beilstein C, Boerma C, Chiche JD, et al. Relationship between norepinephrine dose, tachycardia and outcome in septic shock: a multicentre evaluation. J Crit Care. 2020; 57: 185–190. https://doi.org/10.1016/j.jcrc.2020.02.014
- 28De Backer D, Creteur J, Silva E, Vincent JL. Effects of dopamine, norepinephrine, and epinephrine on the splanchnic circulation in septic shock: which is best? Crit Care Med. 2003; 31(6): 1659–1667. https://doi.org/10.1097/01.CCM.0000063045.77339.B6
- 29Kurita T, Kawashima S, Khaleelullah MMSI, Nakajima Y. Impact of high-dose vasopressor during endotoxic shock on the cerebral, lingual, hepatic, and renal microcirculation evaluated by near-infrared spectroscopy in swine. Shock. 2024; 61(3): 406–413. https://doi.org/10.1097/SHK.0000000000002282
- 30Shoji H, Tani T, Hanasawa K, Kodama M. Extracorporeal endotoxin removal by polymyxin B immobilized fiber cartridge: designing and antiendotoxin efficacy in the clinical application. Ther Apher. 1998; 2(1): 3–12. https://doi.org/10.1111/j.1744-9987.1998.tb00066.x
- 31Yamashita C, Moriyama K, Hasegawa D, Kato Y, Sakai T, Kawaji T, et al. In vitro study of endotoxin adsorption by a polymyxin B-immobilized fiber column. Blood Purif. 2018; 46(4): 269–273. https://doi.org/10.1159/000489920
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