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Xing H, Wei Y, Zhang D, Jiang Z, Qin J, Ou S, Wu W. Comparing adsorptive blood purification modalities for sepsis patients: A systematic review and network meta-analysis. Respir Med 2025; 239:107994. [PMID: 39952412 DOI: 10.1016/j.rmed.2025.107994] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/08/2024] [Revised: 02/07/2025] [Accepted: 02/11/2025] [Indexed: 02/17/2025]
Abstract
PURPOSE Hemoadsorption is a promising therapeutic modality for sepsis, however, the most effective approach is unknown. This meta-analysis aimed to compare the efficacy of different adsorptive blood purification (ABP) modalities in patients with sepsis. MATERIALS AND METHODS Randomized controlled trials (RCTs) investigating the clinical efficacy of ABP modalities in patients with sepsis were retrieved from English databases from inception up to October 14, 2024. The data were analyzed using Stata15 and R software. Quality assessment and publication bias were assessed using the Cochrane Risk of Bias Assessment Tool and funnel plots, respectively. The outcomes of the meta-analysis were hospital mortality, oxygenation index, ICU stay days, and blood lactate concentration. RESULTS A total of 47 RCTs were identified, comprising 9 ABP modalities. In terms of cumulative ranking probability, the HA330 modality achieved the highest reduction in hospital mortality (99.5 %) and ICU stay days (97.2 %), whereas CPFA showed the highest reduction in oxygenation index (94.9 %) and oXiris had the highest reduction in lactate (95.7 %). CONCLUSIONS HA330 and PMX showed superior overall efficacy in sepsis patients compared with other modalities, although there was potential heterogeneity. However, further RCTs with large samples are advocated to test new approaches of hemosorption and validate the present findings.
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Affiliation(s)
- Huameng Xing
- Department of Nephrology, Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, 646000, China; Sichuan Clinical Research Center for Kidney Disease, Luzhou, Sichuan, 646000, China; Department of Nephrology, The First People's Hospital of Zigong, Zigong, Sichuan, 646000, China
| | - Yuxuan Wei
- Department of Nephrology, Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, 646000, China; Sichuan Clinical Research Center for Kidney Disease, Luzhou, Sichuan, 646000, China
| | - Dongmei Zhang
- Department of Nephrology, Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, 646000, China; Sichuan Clinical Research Center for Kidney Disease, Luzhou, Sichuan, 646000, China
| | - Zheng Jiang
- Department of Nephrology, Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, 646000, China; Sichuan Clinical Research Center for Kidney Disease, Luzhou, Sichuan, 646000, China
| | - Jianhua Qin
- Department of Nephrology, Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, 646000, China; Sichuan Clinical Research Center for Kidney Disease, Luzhou, Sichuan, 646000, China
| | - Santao Ou
- Department of Nephrology, Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, 646000, China; Sichuan Clinical Research Center for Kidney Disease, Luzhou, Sichuan, 646000, China
| | - Weihua Wu
- Department of Nephrology, Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, 646000, China; Sichuan Clinical Research Center for Kidney Disease, Luzhou, Sichuan, 646000, China.
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Shime N, Nakada TA, Yatabe T, Yamakawa K, Aoki Y, Inoue S, Iba T, Ogura H, Kawai Y, Kawaguchi A, Kawasaki T, Kondo Y, Sakuraya M, Taito S, Doi K, Hashimoto H, Hara Y, Fukuda T, Matsushima A, Egi M, Kushimoto S, Oami T, Kikutani K, Kotani Y, Aikawa G, Aoki M, Akatsuka M, Asai H, Abe T, Amemiya Y, Ishizawa R, Ishihara T, Ishimaru T, Itosu Y, Inoue H, Imahase H, Imura H, Iwasaki N, Ushio N, Uchida M, Uchi M, Umegaki T, Umemura Y, Endo A, Oi M, Ouchi A, Osawa I, Oshima Y, Ota K, Ohno T, Okada Y, Okano H, Ogawa Y, Kashiura M, Kasugai D, Kano KI, Kamidani R, Kawauchi A, Kawakami S, Kawakami D, Kawamura Y, Kandori K, Kishihara Y, Kimura S, Kubo K, Kuribara T, Koami H, Koba S, Sato T, Sato R, Sawada Y, Shida H, Shimada T, Shimizu M, Shimizu K, Shiraishi T, Shinkai T, Tampo A, Sugiura G, Sugimoto K, Sugimoto H, Suhara T, Sekino M, Sonota K, Taito M, Takahashi N, Takeshita J, Takeda C, Tatsuno J, Tanaka A, Tani M, Tanikawa A, Chen H, Tsuchida T, Tsutsumi Y, Tsunemitsu T, Deguchi R, Tetsuhara K, Terayama T, Togami Y, et alShime N, Nakada TA, Yatabe T, Yamakawa K, Aoki Y, Inoue S, Iba T, Ogura H, Kawai Y, Kawaguchi A, Kawasaki T, Kondo Y, Sakuraya M, Taito S, Doi K, Hashimoto H, Hara Y, Fukuda T, Matsushima A, Egi M, Kushimoto S, Oami T, Kikutani K, Kotani Y, Aikawa G, Aoki M, Akatsuka M, Asai H, Abe T, Amemiya Y, Ishizawa R, Ishihara T, Ishimaru T, Itosu Y, Inoue H, Imahase H, Imura H, Iwasaki N, Ushio N, Uchida M, Uchi M, Umegaki T, Umemura Y, Endo A, Oi M, Ouchi A, Osawa I, Oshima Y, Ota K, Ohno T, Okada Y, Okano H, Ogawa Y, Kashiura M, Kasugai D, Kano KI, Kamidani R, Kawauchi A, Kawakami S, Kawakami D, Kawamura Y, Kandori K, Kishihara Y, Kimura S, Kubo K, Kuribara T, Koami H, Koba S, Sato T, Sato R, Sawada Y, Shida H, Shimada T, Shimizu M, Shimizu K, Shiraishi T, Shinkai T, Tampo A, Sugiura G, Sugimoto K, Sugimoto H, Suhara T, Sekino M, Sonota K, Taito M, Takahashi N, Takeshita J, Takeda C, Tatsuno J, Tanaka A, Tani M, Tanikawa A, Chen H, Tsuchida T, Tsutsumi Y, Tsunemitsu T, Deguchi R, Tetsuhara K, Terayama T, Togami Y, Totoki T, Tomoda Y, Nakao S, Nagasawa H, Nakatani Y, Nakanishi N, Nishioka N, Nishikimi M, Noguchi S, Nonami S, Nomura O, Hashimoto K, Hatakeyama J, Hamai Y, Hikone M, Hisamune R, Hirose T, Fuke R, Fujii R, Fujie N, Fujinaga J, Fujinami Y, Fujiwara S, Funakoshi H, Homma K, Makino Y, Matsuura H, Matsuoka A, Matsuoka T, Matsumura Y, Mizuno A, Miyamoto S, Miyoshi Y, Murata S, Murata T, Yakushiji H, Yasuo S, Yamada K, Yamada H, Yamamoto R, Yamamoto R, Yumoto T, Yoshida Y, Yoshihiro S, Yoshimura S, Yoshimura J, Yonekura H, Wakabayashi Y, Wada T, Watanabe S, Ijiri A, Ugata K, Uda S, Onodera R, Takahashi M, Nakajima S, Honda J, Matsumoto T. The Japanese Clinical Practice Guidelines for Management of Sepsis and Septic Shock 2024. J Intensive Care 2025; 13:15. [PMID: 40087807 PMCID: PMC11907869 DOI: 10.1186/s40560-025-00776-0] [Show More Authors] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/13/2024] [Accepted: 01/21/2025] [Indexed: 03/17/2025] Open
Abstract
The 2024 revised edition of the Japanese Clinical Practice Guidelines for Management of Sepsis and Septic Shock (J-SSCG 2024) is published by the Japanese Society of Intensive Care Medicine and the Japanese Association for Acute Medicine. This is the fourth revision since the first edition was published in 2012. The purpose of the guidelines is to assist healthcare providers in making appropriate decisions in the treatment of sepsis and septic shock, leading to improved patient outcomes. We aimed to create guidelines that are easy to understand and use for physicians who recognize sepsis and provide initial management, specialized physicians who take over the treatment, and multidisciplinary healthcare providers, including nurses, physical therapists, clinical engineers, and pharmacists. The J-SSCG 2024 covers the following nine areas: diagnosis of sepsis and source control, antimicrobial therapy, initial resuscitation, blood purification, disseminated intravascular coagulation, adjunctive therapy, post-intensive care syndrome, patient and family care, and pediatrics. In these areas, we extracted 78 important clinical issues. The GRADE (Grading of Recommendations Assessment, Development and Evaluation) method was adopted for making recommendations, and the modified Delphi method was used to determine recommendations by voting from all committee members. As a result, 42 GRADE-based recommendations, 7 good practice statements, and 22 information-to-background questions were created as responses to clinical questions. We also described 12 future research questions.
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Affiliation(s)
- Nobuaki Shime
- Department of Emergency and Critical Care Medicine, Graduate School of Biomedical and Health Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima, 734-8551, Japan.
| | - Taka-Aki Nakada
- Department of Emergency and Critical Care Medicine, Chiba University Graduate School of Medicine, Chiba, Japan
| | - Tomoaki Yatabe
- Emergency Department, Nishichita General Hospital, Tokai, Japan
| | - Kazuma Yamakawa
- Department of Emergency and Critical Care Medicine, Osaka Medical and Pharmaceutical University, Takatsuki, Japan
| | - Yoshitaka Aoki
- Department of Anesthesiology and Intensive Care Medicine, Hamamatsu University School of Medicine, Hamamatsu, Japan
| | - Shigeaki Inoue
- Department of Emergency and Critical Care Medicine, Wakayama Medical University, Wakayama, Japan
| | - Toshiaki Iba
- Department of Emergency and Disaster Medicine, Juntendo University, Tokyo, Japan
| | - Hiroshi Ogura
- Department of Traumatology and Acute Critical Medicine, Osaka University Graduate School of Medicine, Suita, Japan
| | - Yusuke Kawai
- Department of Nursing, Fujita Health University Hospital, Toyoake, Japan
| | - Atsushi Kawaguchi
- Division of Pediatric Critical Care, Department of Pediatrics, School of Medicine, St. Marianna University, Kawasaki, Japan
| | - Tatsuya Kawasaki
- Department of Pediatric Critical Care, Shizuoka Children's Hospital, Shizuoka, Japan
| | - Yutaka Kondo
- Department of Emergency and Critical Care Medicine, Juntendo University, Urayasu Hospital, Urayasu, Japan
| | - Masaaki Sakuraya
- Department of Emergency and Intensive Care Medicine, JA Hiroshima General Hospital, Hatsukaichi, Japan
| | - Shunsuke Taito
- Division of Rehabilitation, Department of Clinical Practice and Support, Hiroshima University Hospital, Hiroshima, Japan
| | - Kent Doi
- Department of Emergency and Critical Care Medicine, The University of Tokyo, Tokyo, Japan
| | - Hideki Hashimoto
- Department of Infectious Diseases, Hitachi Medical Education and Research Center University of Tsukuba Hospital, Hitachi, Japan
| | - Yoshitaka Hara
- Department of Anesthesiology and Critical Care Medicine, Fujita Health University School of Medicine, Toyoake, Japan
| | - Tatsuma Fukuda
- Department of Emergency and Critical Care Medicine, Toranomon Hospital, Tokyo, Japan
| | - Asako Matsushima
- Department of Emergency and Critical Care, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan
| | - Moritoki Egi
- Department of Anesthesia and Intensive Care, Kyoto University Hospital, Kyoto, Japan
| | - Shigeki Kushimoto
- Division of Emergency and Critical Care Medicine, Tohoku University Graduate School of Medicine, Sendai, Japan
| | - Takehiko Oami
- Department of Emergency and Critical Care Medicine, Chiba University Graduate School of Medicine, Chiba, Japan
| | - Kazuya Kikutani
- Department of Emergency and Critical Care Medicine, Graduate School of Biomedical and Health Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima, 734-8551, Japan
| | - Yuki Kotani
- Department of Intensive Care Medicine Kameda Medical Center, Kamogawa, Japan
| | - Gen Aikawa
- Department of Adult Health Nursing, College of Nursing, Ibaraki Christian University, Hitachi, Japan
| | - Makoto Aoki
- Division of Traumatology, National Defense Medical College Research Institute, Tokorozawa, Japan
| | - Masayuki Akatsuka
- Department of Intensive Care Medicine, Sapporo Medical University School of Medicine, Sapporo, Japan
| | - Hideki Asai
- Department of Emergency and Critical Care Medicine, Nara Medical University, Nara, Japan
| | - Toshikazu Abe
- Department of Emergency and Critical Care Medicine, Tsukuba Memorial Hospital, Tsukuba, Japan
| | - Yu Amemiya
- Department of Emergency and Critical Care Medicine, Osaka Medical and Pharmaceutical University, Takatsuki, Japan
| | - Ryo Ishizawa
- Department of Critical Care and Emergency Medicine, Tokyo Metropolitan Tama Medical Center, Tokyo, Japan
| | - Tadashi Ishihara
- Department of Emergency and Critical Care Medicine, Juntendo University, Urayasu Hospital, Urayasu, Japan
| | - Tadayoshi Ishimaru
- Department of Emergency Medicine, Chiba Kaihin Municipal Hospital, Chiba, Japan
| | - Yusuke Itosu
- Department of Anesthesiology, Hokkaido University Hospital, Sapporo, Japan
| | - Hiroyasu Inoue
- Division of Physical Therapy, Department of Rehabilitation, Showa University School of Nursing and Rehabilitation Sciences, Yokohama, Japan
| | - Hisashi Imahase
- Division of Intensive Care, Department of Anesthesiology and Intensive Care Medicine, Jichi Medical University School of Medicine, Shimotsuke, Japan
| | - Haruki Imura
- Department of Infectious Diseases, Rakuwakai Otowa Hospital, Kyoto, Japan
| | - Naoya Iwasaki
- Department of Anesthesiology and Intensive Care Medicine, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan
| | - Noritaka Ushio
- Department of Emergency and Critical Care Medicine, Osaka Medical and Pharmaceutical University, Takatsuki, Japan
| | - Masatoshi Uchida
- Department of Emergency and Critical Care Medicine, Dokkyo Medical University, Tochigi, Japan
| | - Michiko Uchi
- National Hospital Organization Ibarakihigashi National Hospital, Naka-Gun, Japan
| | - Takeshi Umegaki
- Department of Anesthesiology, Kansai Medical University, Hirakata, Japan
| | - Yutaka Umemura
- Division of Trauma and Surgical Critical Care, Osaka General Medical Center, Osaka, Japan
| | - Akira Endo
- Department of Acute Critical Care Medicine, Tsuchiura Kyodo General Hospital, Tsuchiura, Japan
| | - Marina Oi
- Department of Emergency and Critical Care Medicine, Kitasato University School of Medicine, Sagamihara, Japan
| | - Akira Ouchi
- Department of Adult Health Nursing, College of Nursing, Ibaraki Christian University, Hitachi, Japan
| | - Itsuki Osawa
- Department of Emergency and Critical Care Medicine, The University of Tokyo, Tokyo, Japan
| | | | - Kohei Ota
- Department of Emergency and Critical Care Medicine, Graduate School of Biomedical and Health Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima, 734-8551, Japan
| | - Takanori Ohno
- Department of Emergency and Crical Care Medicine, Shin-Yurigaoka General Hospital, Kawasaki, Japan
| | - Yohei Okada
- Department of Preventive Services, Kyoto University, Kyoto, Japan
| | - Hiromu Okano
- Department of Critical Care Medicine, St. Luke's International Hospital, Tokyo, Japan
| | - Yoshihito Ogawa
- Division of Trauma and Surgical Critical Care, Osaka General Medical Center, Osaka, Japan
| | - Masahiro Kashiura
- Department of Emergency and Critical Care Medicine, Jichi Medical University Saitama Medical Center, Saitama, Japan
| | - Daisuke Kasugai
- Department of Emergency and Critical Care Medicine, Nagoya University Graduate School of Medicine, Nagoya, Japan
| | - Ken-Ichi Kano
- Department of Emergency Medicine, Fukui Prefectural Hospital, Fukui, Japan
| | - Ryo Kamidani
- Department of Emergency and Disaster Medicine, Gifu University Graduate School of Medicine, Gifu, Japan
| | - Akira Kawauchi
- Department of Critical Care and Emergency Medicine, Japanese Red Cross Maebashi Hospital, Maebashi, Japan
| | - Sadatoshi Kawakami
- Department of Anesthesiology, Cancer Institute Hospital of Japanese Foundation for Cancer Research, Tokyo, Japan
| | - Daisuke Kawakami
- Department of Intensive Care Medicine, Aso Iizuka Hospital, Iizuka, Japan
| | - Yusuke Kawamura
- Department of Rehabilitation, Showa General Hospital, Tokyo, Japan
| | - Kenji Kandori
- Department of Emergency and Critical Care Medicine, Japanese Red Cross Society Kyoto Daini Hospital , Kyoto, Japan
| | - Yuki Kishihara
- Department of Emergency and Critical Care Medicine, Jichi Medical University Saitama Medical Center, Saitama, Japan
| | - Sho Kimura
- Department of Pediatric Critical Care Medicine, Tokyo Women's Medical University Yachiyo Medical Center, Yachiyo, Japan
| | - Kenji Kubo
- Department of Emergency Medicine, Japanese Red Cross Wakayama Medical Center, Wakayama, Japan
- Department of Infectious Diseases, Japanese Red Cross Wakayama Medical Center, Wakayama, Japan
| | - Tomoki Kuribara
- Department of Acute and Critical Care Nursing, School of Nursing, Sapporo City University, Sapporo, Japan
| | - Hiroyuki Koami
- Department of Emergency and Critical Care Medicine, Saga University, Saga, Japan
| | - Shigeru Koba
- Department of Critical Care Medicine, Nerima Hikarigaoka Hospital, Nerima, Japan
| | - Takehito Sato
- Department of Anesthesiology, Nagoya University Hospital, Nagoya, Japan
| | - Ren Sato
- Department of Nursing, Tokyo Medical University Hospital, Shinjuku, Japan
| | - Yusuke Sawada
- Department of Emergency Medicine, Gunma University Graduate School of Medicine, Maebashi, Japan
| | - Haruka Shida
- Data Science, Medical Division, AstraZeneca K.K, Osaka, Japan
| | - Tadanaga Shimada
- Department of Emergency and Critical Care Medicine, Chiba University Graduate School of Medicine, Chiba, Japan
| | - Motohiro Shimizu
- Department of Intensive Care Medicine, Ryokusen-Kai Yonemori Hospital, Kagoshima, Japan
| | | | | | - Toru Shinkai
- The Advanced Emergency and Critical Care Center, Mie University Hospital, Tsu, Japan
| | - Akihito Tampo
- Department of Emergency Medicine, Asahiakwa Medical University, Asahikawa, Japan
| | - Gaku Sugiura
- Department of Critical Care and Emergency Medicine, Japanese Red Cross Maebashi Hospital, Maebashi, Japan
| | - Kensuke Sugimoto
- Department of Anesthesiology and Intensive Care, Gunma University, Maebashi, Japan
| | - Hiroshi Sugimoto
- Department of Internal Medicine, National Hospital Organization Kinki-Chuo Chest Medical Center, Osaka, Japan
| | - Tomohiro Suhara
- Department of Anesthesiology, Keio University School of Medicine, Shinjuku, Japan
| | - Motohiro Sekino
- Department of Anesthesiology and Intensive Care Medicine, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan
| | - Kenji Sonota
- Department of Intensive Care Medicine, Miyagi Children's Hospital, Sendai, Japan
| | - Mahoko Taito
- Department of Nursing, Hiroshima University Hospital, Hiroshima, Japan
| | - Nozomi Takahashi
- Centre for Heart Lung Innovation, University of British Columbia, Vancouver, British Columbia, Canada
| | - Jun Takeshita
- Department of Anesthesiology, Osaka Women's and Children's Hospital, Izumi, Japan
| | - Chikashi Takeda
- Department of Anesthesia and Intensive Care, Kyoto University Hospital, Kyoto, Japan
| | - Junko Tatsuno
- Department of Nursing, Kokura Memorial Hospital, Kitakyushu, Japan
| | - Aiko Tanaka
- Department of Intensive Care, University of Fukui Hospital, Fukui, Japan
| | - Masanori Tani
- Division of Critical Care Medicine, Saitama Children's Medical Center, Saitama, Japan
| | - Atsushi Tanikawa
- Division of Emergency and Critical Care Medicine, Tohoku University Graduate School of Medicine, Sendai, Japan
| | - Hao Chen
- Department of Pulmonary, Yokohama City University Hospital, Yokohama, Japan
| | - Takumi Tsuchida
- Department of Anesthesiology, Hokkaido University Hospital, Sapporo, Japan
| | - Yusuke Tsutsumi
- Department of Emergency Medicine, National Hospital Organization Mito Medical Center, Ibaragi, Japan
| | | | - Ryo Deguchi
- Department of Traumatology and Critical Care Medicine, Osaka Metropolitan University Hospital, Osaka, Japan
| | - Kenichi Tetsuhara
- Department of Critical Care Medicine, Fukuoka Children's Hospital, Fukuoka, Japan
| | - Takero Terayama
- Department of Emergency Self-Defense, Forces Central Hospital, Tokyo, Japan
| | - Yuki Togami
- Department of Acute Medicine & Critical Care Medical Center, National Hospital Organization Osaka National Hospital, Osaka, Japan
| | - Takaaki Totoki
- Department of Anesthesiology, Kyushu University Beppu Hospital, Beppu, Japan
| | - Yoshinori Tomoda
- Laboratory of Clinical Pharmacokinetics, Research and Education Center for Clinical Pharmacy, Kitasato University School of Pharmacy, Tokyo, Japan
| | - Shunichiro Nakao
- Department of Traumatology and Acute Critical Medicine, Osaka University Graduate School of Medicine, Suita, Japan
| | - Hiroki Nagasawa
- Department of Acute Critical Care Medicine, Shizuoka Hospital Juntendo University, Shizuoka, Japan
| | | | - Nobuto Nakanishi
- Department of Disaster and Emergency Medicine, Kobe University, Kobe, Japan
| | - Norihiro Nishioka
- Department of Emergency and Crical Care Medicine, Shin-Yurigaoka General Hospital, Kawasaki, Japan
| | - Mitsuaki Nishikimi
- Department of Emergency and Critical Care Medicine, Graduate School of Biomedical and Health Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima, 734-8551, Japan
| | - Satoko Noguchi
- Department of Anesthesiology, Hirosaki University Graduate School of Medicine, Hirosaki, Japan
| | - Suguru Nonami
- Department of Emergency and Critical Care Medicine, Kyoto Katsura Hospital, Kyoto, Japan
| | - Osamu Nomura
- Medical Education Development Center, Gifu University, Gifu, Japan
| | - Katsuhiko Hashimoto
- Department of Emergency and Intensive Care Medicine, Fukushima Medical University, Fukushima, Japan
| | - Junji Hatakeyama
- Department of Emergency and Critical Care Medicine, Osaka Medical and Pharmaceutical University, Takatsuki, Japan
| | - Yasutaka Hamai
- Department of Preventive Services, Kyoto University, Kyoto, Japan
| | - Mayu Hikone
- Department of Emergency Medicine, Tokyo Metropolitan Bokutoh Hospital, Tokyo, Japan
| | - Ryo Hisamune
- Department of Emergency and Critical Care Medicine, Osaka Medical and Pharmaceutical University, Takatsuki, Japan
| | - Tomoya Hirose
- Department of Traumatology and Acute Critical Medicine, Osaka University Graduate School of Medicine, Suita, Japan
| | - Ryota Fuke
- Department of Internal Medicine, IMS Meirikai Sendai General Hospital, Sendai, Japan
| | - Ryo Fujii
- Emergency Department, Ageo Central General Hospital, Ageo, Japan
| | - Naoki Fujie
- Department of Pharmacy, Osaka Psychiatric Medical Center, Hirakata, Japan
| | - Jun Fujinaga
- Emergency and Critical Care Center, Kurashiki Central Hospital, Kurashiki, Japan
| | - Yoshihisa Fujinami
- Department of Emergency Medicine, Kakogawa Central City Hospital, Kakogawa, Japan
| | - Sho Fujiwara
- Department of Emergency Medicine, Tokyo Hikifune Hospital, Tokyo, Japan
- Department of Infectious Diseases, Tokyo Hikifune Hospital, Tokyo, Japan
| | - Hiraku Funakoshi
- Department of Emergency and Critical Care Medicine, Tokyobay Urayasu Ichikawa Medical Center, Urayasu, Japan
| | - Koichiro Homma
- Department of Emergency and Critical Care Medicine, Keio University School of Medicine, Shinjuku, Japan
| | - Yuto Makino
- Department of Preventive Services, Kyoto University, Kyoto, Japan
| | - Hiroshi Matsuura
- Osaka Prefectural Nakakawachi Emergency and Critical Care Center, Higashiosaka, Japan
| | - Ayaka Matsuoka
- Department of Emergency and Critical Care Medicine, Saga University, Saga, Japan
| | - Tadashi Matsuoka
- Department of Emergency and Critical Care Medicine, Keio University School of Medicine, Shinjuku, Japan
| | - Yosuke Matsumura
- Department of Intensive Care, Chiba Emergency and Psychiatric Medical Center, Chiba, Japan
| | - Akito Mizuno
- Department of Anesthesia and Intensive Care, Kyoto University Hospital, Kyoto, Japan
| | - Sohma Miyamoto
- Department of Emergency and Critical Care Medicine, St. Luke's International Hospital, Chuo-Ku, Japan
| | - Yukari Miyoshi
- Department of Emergency and Critical Care Medicine, Juntendo University, Urayasu Hospital, Urayasu, Japan
| | - Satoshi Murata
- Division of Emergency Medicine, Hyogo Prefectural Kobe Children's Hospital, Kobe, Japan
| | - Teppei Murata
- Department of Cardiology Miyazaki Prefectural, Nobeoka Hospital, Nobeoka, Japan
| | | | | | - Kohei Yamada
- Department of Traumatology and Critical Care Medicine, National Defense Medical College Hospital, Saitama, Japan
| | - Hiroyuki Yamada
- Department of Primary Care and Emergency Medicine, Graduate School of Medicine, Kyoto University, Kyoto, Japan
| | - Ryo Yamamoto
- Department of Emergency and Critical Care Medicine, Keio University School of Medicine, Shinjuku, Japan
| | - Ryohei Yamamoto
- Center for Innovative Research for Communities and Clinical Excellence (CIRC2LE), Fukushima Medical University, Fukushima, Japan
| | - Tetsuya Yumoto
- Department of Emergency, Critical Care and Disaster Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Okayama, Japan
| | - Yuji Yoshida
- Department of Anesthesia and Intensive Care, Kyoto University Hospital, Kyoto, Japan
| | - Shodai Yoshihiro
- Department of Pharmaceutical Services, Hiroshima University Hospital, Hiroshima, Japan
| | - Satoshi Yoshimura
- Department of Emergency Medicine, Rakuwakai Otowa Hospital, Kyoto, Japan
| | - Jumpei Yoshimura
- Department of Traumatology and Acute Critical Medicine, Osaka University Graduate School of Medicine, Suita, Japan
| | - Hiroshi Yonekura
- Department of Anesthesiology and Pain Medicine, Fujita Health University Bantane Hospital, Nagoya, Japan
| | - Yuki Wakabayashi
- Department of Nursing, Kobe City Medical Center General Hospital, Kobe, Japan
| | - Takeshi Wada
- Division of Acute and Critical Care Medicine, Department of Anesthesiology and Critical Care Medicine, Faculty of Medicine, Hokkaido University, Sapporo, Japan
| | - Shinichi Watanabe
- Department of Physical Therapy, Faculty of Rehabilitation Gifu, University of Health Science, Gifu, Japan
| | - Atsuhiro Ijiri
- Department of Traumatology and Critical Care Medicine, National Defense Medical College Hospital, Saitama, Japan
| | - Kei Ugata
- Department of Intensive Care Medicine, Matsue Red Cross Hospital, Matsue, Japan
| | - Shuji Uda
- Department of Anesthesia and Intensive Care, Kyoto University Hospital, Kyoto, Japan
| | - Ryuta Onodera
- Department of Preventive Services, Kyoto University, Kyoto, Japan
| | - Masaki Takahashi
- Division of Acute and Critical Care Medicine, Department of Anesthesiology and Critical Care Medicine, Faculty of Medicine, Hokkaido University, Sapporo, Japan
| | - Satoshi Nakajima
- Department of Emergency Medicine, Kyoto Prefectural University of Medicine, Kyoto, Japan
| | - Junta Honda
- Department of Emergency and Critical Care Medicine, Nagoya University Graduate School of Medicine, Nagoya, Japan
| | - Tsuguhiro Matsumoto
- Department of Anesthesia and Intensive Care, Kyoto University Hospital, Kyoto, Japan
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Li C, Zhang J, Yang P, Wang R, Chen T, Li L. The role of polymyxin B-immobilized hemoperfusion in reducing mortality and enhancing hemodynamics in patients with sepsis and septic shock: A systematic review and meta-analysis. Heliyon 2024; 10:e33735. [PMID: 39040355 PMCID: PMC11261863 DOI: 10.1016/j.heliyon.2024.e33735] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/02/2024] [Revised: 05/17/2024] [Accepted: 06/26/2024] [Indexed: 07/24/2024] Open
Abstract
Purpose Polymyxin B-immobilized hemoperfusion (PMX-HP) is a therapeutic strategy for removing circulating endotoxins from patients with sepsis or septic shock. However, the survival advantage of PMX-HP treatment remains controversial for patients with sepsis/septic shock. Therefore, this study collected all the clinical trials to assess the effect and the safety of PMX-HP treatment. Methods PubMed, EMBASE, and the Cochrane Central Register of Controlled Trials were searched for eligible trials fromtheir inception through June 30, 2023. All clinical trials that investigated the effect of polymyxin B hemoperfusion in patients who died with sepsis or septic shock within 28-day mortality were eligible. The Cochrane Risk of Bias Assessment instrument and the ROBINS-I tool were used to assess the risk of bias. Results A total of 30 trials, including 25680 adult patients, were included. PMX-HP decreased 28-day mortality (OR 0.75, 95 % CI 0.65-0.88; p<0.00001). Subgroup analysis revealed that 28-day mortality was significantly reduced after PMX-HP treatment in the mixed infection site group and in the age under 70 years old group. PMX-HP might also lower endotoxin levels (MD -1.22, 95 % CI -1.62 - 0.81, p < 0.00001) and improve SOFA scores (MD -2.11, 95 % CI -3.80- 0.43, p = 0.01). PMX-HP was not linked to the development of significant adverse events (p = 0. 05). Conclusion Our findings suggest that PMX-HP therapy can reduce 28-day mortality in individuals with sepsis or septic shock. The therapeutic effect may be due to the ability of PMX-HP to lower endotoxin levels and enhance hemodynamics. However, further assessment of the clinical effects of PMX-HP on sepsis or septic shock is required.
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Affiliation(s)
- Chao Li
- Department of Clinical Pharmacy, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Jinlian Zhang
- Department of Clinical Pharmacy, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Ping Yang
- Department of Clinical Pharmacy, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Ranran Wang
- Department of Clinical Pharmacy, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Ting Chen
- Department of Clinical Pharmacy, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Lixia Li
- Department of Clinical Pharmacy, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
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4
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Chen JJ, Lai PC, Lee TH, Huang YT. Blood Purification for Adult Patients With Severe Infection or Sepsis/Septic Shock: A Network Meta-Analysis of Randomized Controlled Trials. Crit Care Med 2023; 51:1777-1789. [PMID: 37470680 PMCID: PMC10645104 DOI: 10.1097/ccm.0000000000005991] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 07/21/2023]
Abstract
OBJECTIVES This study aimed to conduct a comprehensive and updated systematic review with network meta-analysis (NMA) to assess the outcome benefits of various blood purification modalities for adult patients with severe infection or sepsis. DATA SOURCES We conducted a search of PubMed, MEDLINE, clinical trial registries, Cochrane Library, and Embase databases with no language restrictions. STUDY SELECTION Only randomized controlled trials (RCTs) were selected. DATA EXTRACTION The primary outcome was overall mortality. The secondary outcomes were the length of mechanical ventilation (MV) days and ICU stay, incidence of acute kidney injury (AKI), and kidney replacement therapy requirement. DATA SYNTHESIS We included a total of 60 RCTs with 4,595 participants, comparing 16 blood purification modalities with 17 interventions. Polymyxin-B hemoperfusion (relative risk [RR]: 0.70; 95% CI, 0.57-0.86) and plasma exchange (RR: 0.61; 95% CI, 0.42-0.91) were associated with low mortality (very low and low certainty of evidence, respectively). Because of the presence of high clinical heterogeneity and intransitivity, the potential benefit of polymyxin-B hemoperfusion remained inconclusive. The analysis of secondary outcomes was limited by the scarcity of available studies. HA330 with high-volume continuous venovenous hemofiltration (CVVH), HA330, and standard-volume CVVH were associated with shorter ICU stay. HA330 with high-volume CVVH, HA330, and standard-volume CVVH were beneficial in reducing MV days. None of the interventions showed a significant reduction in the incidence of AKI or the need for kidney replacement therapy. CONCLUSIONS Our NMA suggests that plasma exchange and polymyxin-B hemoperfusion may provide potential benefits for adult patients with severe infection or sepsis/septic shock when compared with standard care alone, but most comparisons were based on low or very low certainty evidence. The therapeutic effect of polymyxin-B hemoperfusion remains uncertain. Further RCTs are required to identify the specific patient population that may benefit from extracorporeal blood purification.
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Affiliation(s)
- Jia-Jin Chen
- Department of Nephrology, Chang Gung Memorial Hospital, Linkou Main Branch, Taoyuan City, Taiwan
| | - Pei-Chun Lai
- Education Center, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan
| | | | - Yen-Ta Huang
- Department of Surgery, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan
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5
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Egi M, Ogura H, Yatabe T, Atagi K, Inoue S, Iba T, Kakihana Y, Kawasaki T, Kushimoto S, Kuroda Y, Kotani J, Shime N, Taniguchi T, Tsuruta R, Doi K, Doi M, Nakada TA, Nakane M, Fujishima S, Hosokawa N, Masuda Y, Matsushima A, Matsuda N, Yamakawa K, Hara Y, Sakuraya M, Ohshimo S, Aoki Y, Inada M, Umemura Y, Kawai Y, Kondo Y, Saito H, Taito S, Takeda C, Terayama T, Tohira H, Hashimoto H, Hayashida K, Hifumi T, Hirose T, Fukuda T, Fujii T, Miura S, Yasuda H, Abe T, Andoh K, Iida Y, Ishihara T, Ide K, Ito K, Ito Y, Inata Y, Utsunomiya A, Unoki T, Endo K, Ouchi A, Ozaki M, Ono S, Katsura M, Kawaguchi A, Kawamura Y, Kudo D, Kubo K, Kurahashi K, Sakuramoto H, Shimoyama A, Suzuki T, Sekine S, Sekino M, Takahashi N, Takahashi S, Takahashi H, Tagami T, Tajima G, Tatsumi H, Tani M, Tsuchiya A, Tsutsumi Y, Naito T, Nagae M, Nagasawa I, Nakamura K, Nishimura T, Nunomiya S, Norisue Y, Hashimoto S, Hasegawa D, Hatakeyama J, Hara N, Higashibeppu N, Furushima N, Furusono H, Matsuishi Y, Matsuyama T, Minematsu Y, Miyashita R, Miyatake Y, Moriyasu M, Yamada T, et alEgi M, Ogura H, Yatabe T, Atagi K, Inoue S, Iba T, Kakihana Y, Kawasaki T, Kushimoto S, Kuroda Y, Kotani J, Shime N, Taniguchi T, Tsuruta R, Doi K, Doi M, Nakada TA, Nakane M, Fujishima S, Hosokawa N, Masuda Y, Matsushima A, Matsuda N, Yamakawa K, Hara Y, Sakuraya M, Ohshimo S, Aoki Y, Inada M, Umemura Y, Kawai Y, Kondo Y, Saito H, Taito S, Takeda C, Terayama T, Tohira H, Hashimoto H, Hayashida K, Hifumi T, Hirose T, Fukuda T, Fujii T, Miura S, Yasuda H, Abe T, Andoh K, Iida Y, Ishihara T, Ide K, Ito K, Ito Y, Inata Y, Utsunomiya A, Unoki T, Endo K, Ouchi A, Ozaki M, Ono S, Katsura M, Kawaguchi A, Kawamura Y, Kudo D, Kubo K, Kurahashi K, Sakuramoto H, Shimoyama A, Suzuki T, Sekine S, Sekino M, Takahashi N, Takahashi S, Takahashi H, Tagami T, Tajima G, Tatsumi H, Tani M, Tsuchiya A, Tsutsumi Y, Naito T, Nagae M, Nagasawa I, Nakamura K, Nishimura T, Nunomiya S, Norisue Y, Hashimoto S, Hasegawa D, Hatakeyama J, Hara N, Higashibeppu N, Furushima N, Furusono H, Matsuishi Y, Matsuyama T, Minematsu Y, Miyashita R, Miyatake Y, Moriyasu M, Yamada T, Yamada H, Yamamoto R, Yoshida T, Yoshida Y, Yoshimura J, Yotsumoto R, Yonekura H, Wada T, Watanabe E, Aoki M, Asai H, Abe T, Igarashi Y, Iguchi N, Ishikawa M, Ishimaru G, Isokawa S, Itakura R, Imahase H, Imura H, Irinoda T, Uehara K, Ushio N, Umegaki T, Egawa Y, Enomoto Y, Ota K, Ohchi Y, Ohno T, Ohbe H, Oka K, Okada N, Okada Y, Okano H, Okamoto J, Okuda H, Ogura T, Onodera Y, Oyama Y, Kainuma M, Kako E, Kashiura M, Kato H, Kanaya A, Kaneko T, Kanehata K, Kano KI, Kawano H, Kikutani K, Kikuchi H, Kido T, Kimura S, Koami H, Kobashi D, Saiki I, Sakai M, Sakamoto A, Sato T, Shiga Y, Shimoto M, Shimoyama S, Shoko T, Sugawara Y, Sugita A, Suzuki S, Suzuki Y, Suhara T, Sonota K, Takauji S, Takashima K, Takahashi S, Takahashi Y, Takeshita J, Tanaka Y, Tampo A, Tsunoyama T, Tetsuhara K, Tokunaga K, Tomioka Y, Tomita K, Tominaga N, Toyosaki M, Toyoda Y, Naito H, Nagata I, Nagato T, Nakamura Y, Nakamori Y, Nahara I, Naraba H, Narita C, Nishioka N, Nishimura T, Nishiyama K, Nomura T, Haga T, Hagiwara Y, Hashimoto K, Hatachi T, Hamasaki T, Hayashi T, Hayashi M, Hayamizu A, Haraguchi G, Hirano Y, Fujii R, Fujita M, Fujimura N, Funakoshi H, Horiguchi M, Maki J, Masunaga N, Matsumura Y, Mayumi T, Minami K, Miyazaki Y, Miyamoto K, Murata T, Yanai M, Yano T, Yamada K, Yamada N, Yamamoto T, Yoshihiro S, Tanaka H, Nishida O. The Japanese Clinical Practice Guidelines for Management of Sepsis and Septic Shock 2020 (J-SSCG 2020). J Intensive Care 2021; 9:53. [PMID: 34433491 PMCID: PMC8384927 DOI: 10.1186/s40560-021-00555-7] [Show More Authors] [Citation(s) in RCA: 118] [Impact Index Per Article: 29.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/26/2021] [Accepted: 05/10/2021] [Indexed: 02/08/2023] Open
Abstract
The Japanese Clinical Practice Guidelines for Management of Sepsis and Septic Shock 2020 (J-SSCG 2020), a Japanese-specific set of clinical practice guidelines for sepsis and septic shock created as revised from J-SSCG 2016 jointly by the Japanese Society of Intensive Care Medicine and the Japanese Association for Acute Medicine, was first released in September 2020 and published in February 2021. An English-language version of these guidelines was created based on the contents of the original Japanese-language version. The purpose of this guideline is to assist medical staff in making appropriate decisions to improve the prognosis of patients undergoing treatment for sepsis and septic shock. We aimed to provide high-quality guidelines that are easy to use and understand for specialists, general clinicians, and multidisciplinary medical professionals. J-SSCG 2016 took up new subjects that were not present in SSCG 2016 (e.g., ICU-acquired weakness [ICU-AW], post-intensive care syndrome [PICS], and body temperature management). The J-SSCG 2020 covered a total of 22 areas with four additional new areas (patient- and family-centered care, sepsis treatment system, neuro-intensive treatment, and stress ulcers). A total of 118 important clinical issues (clinical questions, CQs) were extracted regardless of the presence or absence of evidence. These CQs also include those that have been given particular focus within Japan. This is a large-scale guideline covering multiple fields; thus, in addition to the 25 committee members, we had the participation and support of a total of 226 members who are professionals (physicians, nurses, physiotherapists, clinical engineers, and pharmacists) and medical workers with a history of sepsis or critical illness. The GRADE method was adopted for making recommendations, and the modified Delphi method was used to determine recommendations by voting from all committee members.As a result, 79 GRADE-based recommendations, 5 Good Practice Statements (GPS), 18 expert consensuses, 27 answers to background questions (BQs), and summaries of definitions and diagnosis of sepsis were created as responses to 118 CQs. We also incorporated visual information for each CQ according to the time course of treatment, and we will also distribute this as an app. The J-SSCG 2020 is expected to be widely used as a useful bedside guideline in the field of sepsis treatment both in Japan and overseas involving multiple disciplines.
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Affiliation(s)
- Moritoki Egi
- Department of Surgery Related, Division of Anesthesiology, Kobe University Graduate School of Medicine, Kusunoki-cho 7-5-2, Chuo-ku, Kobe, Hyogo, Japan.
| | - Hiroshi Ogura
- Department of Traumatology and Acute Critical Medicine, Osaka University Medical School, Yamadaoka 2-15, Suita, Osaka, Japan.
| | - Tomoaki Yatabe
- Department of Anesthesiology and Critical Care Medicine, Fujita Health University School of Medicine, Toyoake, Japan
| | - Kazuaki Atagi
- Department of Intensive Care Unit, Nara Prefectural General Medical Center, Nara, Japan
| | - Shigeaki Inoue
- Department of Disaster and Emergency Medicine, Kobe University Graduate School of Medicine, Kobe, Japan
| | - Toshiaki Iba
- Department of Emergency and Disaster Medicine, Juntendo University, Tokyo, Japan
| | - Yasuyuki Kakihana
- Department of Emergency and Intensive Care Medicine, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan
| | - Tatsuya Kawasaki
- Department of Pediatric Critical Care, Shizuoka Children's Hospital, Shizuoka, Japan
| | - Shigeki Kushimoto
- Division of Emergency and Critical Care Medicine, Tohoku University Graduate School of Medicine, Sendai, Japan
| | - Yasuhiro Kuroda
- Department of Emergency, Disaster, and Critical Care Medicine, Faculty of Medicine, Kagawa University, Kagawa, Japan
| | - Joji Kotani
- Department of Surgery Related, Division of Disaster and Emergency Medicine, Kobe University Graduate School of Medicine, Kobe, Japan
| | - Nobuaki Shime
- Department of Emergency and Critical Care Medicine, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan
| | - Takumi Taniguchi
- Department of Anesthesiology and Intensive Care Medicine, Kanazawa University, Kanazawa, Japan
| | - Ryosuke Tsuruta
- Acute and General Medicine, Yamaguchi University Graduate School of Medicine, Ube, Japan
| | - Kent Doi
- Department of Acute Medicine, The University of Tokyo, Tokyo, Japan
| | - Matsuyuki Doi
- Department of Anesthesiology and Intensive Care Medicine, Hamamatsu University School of Medicine, Hamamatsu, Japan
| | - Taka-Aki Nakada
- Department of Emergency and Critical Care Medicine, Chiba University Graduate School of Medicine, Chiba, Japan
| | - Masaki Nakane
- Department of Emergency and Critical Care Medicine, Yamagata University Hospital, Yamagata, Japan
| | - Seitaro Fujishima
- Center for General Medicine Education, Keio University School of Medicine, Tokyo, Japan
| | - Naoto Hosokawa
- Department of Infectious Diseases, Kameda Medical Center, Kamogawa, Japan
| | - Yoshiki Masuda
- Department of Intensive Care Medicine, Sapporo Medical University School of Medicine, Sapporo, Japan
| | - Asako Matsushima
- Department of Advancing Acute Medicine, Graduate School of Medical Sciences, Nagoya City University, Nagoya, Japan
| | - Naoyuki Matsuda
- Department of Emergency and Critical Care Medicine, Nagoya University Graduate School of Medicine, Nagoya, Japan
| | - Kazuma Yamakawa
- Department of Emergency Medicine, Osaka Medical College, Osaka, Japan
| | - Yoshitaka Hara
- Department of Anesthesiology and Critical Care Medicine, Fujita Health University School of Medicine, Toyoake, Japan
| | - Masaaki Sakuraya
- Department of Emergency and Intensive Care Medicine, JA Hiroshima General Hospital, Hatsukaichi, Japan
| | - Shinichiro Ohshimo
- Department of Emergency and Critical Care Medicine, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan
| | - Yoshitaka Aoki
- Department of Anesthesiology and Intensive Care Medicine, Hamamatsu University School of Medicine, Hamamatsu, Japan
| | - Mai Inada
- Member of Japanese Association for Acute Medicine, Tokyo, Japan
| | - Yutaka Umemura
- Division of Trauma and Surgical Critical Care, Osaka General Medical Center, Osaka, Japan
| | - Yusuke Kawai
- Department of Nursing, Fujita Health University Hospital, Toyoake, Japan
| | - Yutaka Kondo
- Department of Emergency and Critical Care Medicine, Juntendo University Urayasu Hospital, Urayasu, Japan
| | - Hiroki Saito
- Department of Emergency and Critical Care Medicine, St. Marianna University School of Medicine, Yokohama City Seibu Hospital, Yokohama, Japan
| | - Shunsuke Taito
- Division of Rehabilitation, Department of Clinical Support and Practice, Hiroshima University Hospital, Hiroshima, Japan
| | - Chikashi Takeda
- Department of Anesthesia, Kyoto University Hospital, Kyoto, Japan
| | - Takero Terayama
- Department of Psychiatry, School of Medicine, National Defense Medical College, Tokorozawa, Japan
| | | | - Hideki Hashimoto
- Department of Emergency and Critical Care Medicine/Infectious Disease, Hitachi General Hospital, Hitachi, Japan
| | - Kei Hayashida
- The Feinstein Institute for Medical Research, Manhasset, NY, USA
| | - Toru Hifumi
- Department of Emergency and Critical Care Medicine, St. Luke's International Hospital, Tokyo, Japan
| | - Tomoya Hirose
- Emergency and Critical Care Medical Center, Osaka Police Hospital, Osaka, Japan
| | - Tatsuma Fukuda
- Department of Emergency and Critical Care Medicine, Graduate School of Medicine, University of the Ryukyus, Okinawa, Japan
| | - Tomoko Fujii
- Intensive Care Unit, Jikei University Hospital, Tokyo, Japan
| | - Shinya Miura
- The Royal Children's Hospital Melbourne, Melbourne, Australia
| | - Hideto Yasuda
- Department of Emergency and Critical Care Medicine, Jichi Medical University Saitama Medical Center, Saitama, Japan
| | - Toshikazu Abe
- Department of Emergency and Critical Care Medicine, Tsukuba Memorial Hospital, Tsukuba, Japan
| | - Kohkichi Andoh
- Division of Anesthesiology, Division of Intensive Care, Division of Emergency and Critical Care, Sendai City Hospital, Sendai, Japan
| | - Yuki Iida
- Department of Physical Therapy, School of Health Sciences, Toyohashi Sozo University, Toyohashi, Japan
| | - Tadashi Ishihara
- Department of Emergency and Critical Care Medicine, Juntendo University Urayasu Hospital, Urayasu, Japan
| | - Kentaro Ide
- Critical Care Medicine, National Center for Child Health and Development, Tokyo, Japan
| | - Kenta Ito
- Department of General Pediatrics, Aichi Children's Health and Medical Center, Obu, Japan
| | - Yusuke Ito
- Department of Infectious Disease, Hyogo Prefectural Amagasaki General Medical Center, Amagasaki, Japan
| | - Yu Inata
- Department of Intensive Care Medicine, Osaka Women's and Children's Hospital, Izumi, Japan
| | - Akemi Utsunomiya
- Human Health Science, Graduate School of Medicine, Kyoto University, Kyoto, Japan
| | - Takeshi Unoki
- Department of Acute and Critical Care Nursing, School of Nursing, Sapporo City University, Sapporo, Japan
| | - Koji Endo
- Department of Pharmacoepidemiology, Kyoto University Graduate School of Medicine and Public Health, Kyoto, Japan
| | - Akira Ouchi
- College of Nursing, Ibaraki Christian University, Hitachi, Japan
| | - Masayuki Ozaki
- Department of Emergency and Critical Care Medicine, Komaki City Hospital, Komaki, Japan
| | - Satoshi Ono
- Gastroenterological Center, Shinkuki General Hospital, Kuki, Japan
| | | | | | - Yusuke Kawamura
- Department of Rehabilitation, Showa General Hospital, Tokyo, Japan
| | - Daisuke Kudo
- Division of Emergency and Critical Care Medicine, Tohoku University Graduate School of Medicine, Sendai, Japan
| | - Kenji Kubo
- Department of Emergency Medicine and Department of Infectious Diseases, Japanese Red Cross Wakayama Medical Center, Wakayama, Japan
| | - Kiyoyasu Kurahashi
- Department of Anesthesiology and Intensive Care Medicine, International University of Health and Welfare School of Medicine, Narita, Japan
| | | | - Akira Shimoyama
- Department of Emergency and Critical Care Medicine, Jichi Medical University Saitama Medical Center, Saitama, Japan
| | - Takeshi Suzuki
- Department of Anesthesiology, Tokai University School of Medicine, Isehara, Japan
| | - Shusuke Sekine
- Department of Anesthesiology, Tokyo Medical University, Tokyo, Japan
| | - Motohiro Sekino
- Division of Intensive Care, Nagasaki University Hospital, Nagasaki, Japan
| | - Nozomi Takahashi
- Department of Emergency and Critical Care Medicine, Chiba University Graduate School of Medicine, Chiba, Japan
| | - Sei Takahashi
- Center for Innovative Research for Communities and Clinical Excellence (CiRC2LE), Fukushima Medical University, Fukushima, Japan
| | - Hiroshi Takahashi
- Department of Cardiology, Steel Memorial Muroran Hospital, Muroran, Japan
| | - Takashi Tagami
- Department of Emergency and Critical Care Medicine, Nippon Medical School Musashi Kosugi Hospital, Kawasaki, Japan
| | - Goro Tajima
- Nagasaki University Hospital Acute and Critical Care Center, Nagasaki, Japan
| | - Hiroomi Tatsumi
- Department of Intensive Care Medicine, Sapporo Medical University School of Medicine, Sapporo, Japan
| | - Masanori Tani
- Division of Critical Care Medicine, Saitama Children's Medical Center, Saitama, Japan
| | - Asuka Tsuchiya
- Department of Emergency and Critical Care Medicine, National Hospital Organization Mito Medical Center, Ibaraki, Japan
| | - Yusuke Tsutsumi
- Department of Emergency and Critical Care Medicine, National Hospital Organization Mito Medical Center, Ibaraki, Japan
| | - Takaki Naito
- Department of Emergency and Critical Care Medicine, St. Marianna University School of Medicine, Kawasaki, Japan
| | - Masaharu Nagae
- Department of Intensive Care Medicine, Kobe University Hospital, Kobe, Japan
| | | | - Kensuke Nakamura
- Department of Emergency and Critical Care Medicine, Hitachi General Hospital, Hitachi, Japan
| | - Tetsuro Nishimura
- Department of Traumatology and Critical Care Medicine, Osaka City University Graduate School of Medicine, Osaka, Japan
| | - Shin Nunomiya
- Department of Anesthesiology and Intensive Care Medicine, Division of Intensive Care, Jichi Medical University School of Medicine, Shimotsuke, Japan
| | - Yasuhiro Norisue
- Department of Emergency and Critical Care Medicine, Tokyo Bay Urayasu Ichikawa Medical Center, Urayasu, Japan
| | - Satoru Hashimoto
- Department of Anesthesiology and Intensive Care Medicine, Kyoto Prefectural University of Medicine, Kyoto, Japan
| | - Daisuke Hasegawa
- Department of Anesthesiology and Critical Care Medicine, Fujita Health University School of Medicine, Toyoake, Japan
| | - Junji Hatakeyama
- Department of Emergency and Critical Care Medicine, National Hospital Organization Tokyo Medical Center, Tokyo, Japan
| | - Naoki Hara
- Department of Pharmacy, Yokohama Rosai Hospital, Yokohama, Japan
| | - Naoki Higashibeppu
- Department of Anesthesiology and Nutrition Support Team, Kobe City Medical Center General Hospital, Kobe City Hospital Organization, Kobe, Japan
| | - Nana Furushima
- Department of Anesthesiology, Kobe University Hospital, Kobe, Japan
| | - Hirotaka Furusono
- Department of Rehabilitation, University of Tsukuba Hospital/Exult Co., Ltd., Tsukuba, Japan
| | - Yujiro Matsuishi
- Doctoral program in Clinical Sciences. Graduate School of Comprehensive Human Sciences, University of Tsukuba, Tsukuba, Japan
| | - Tasuku Matsuyama
- Department of Emergency Medicine, Kyoto Prefectural University of Medicine, Kyoto, Japan
| | - Yusuke Minematsu
- Department of Clinical Engineering, Osaka University Hospital, Suita, Japan
| | - Ryoichi Miyashita
- Department of Intensive Care Medicine, Showa University School of Medicine, Tokyo, Japan
| | - Yuji Miyatake
- Department of Clinical Engineering, Kakogawa Central City Hospital, Kakogawa, Japan
| | - Megumi Moriyasu
- Division of Respiratory Care and Rapid Response System, Intensive Care Center, Kitasato University Hospital, Sagamihara, Japan
| | - Toru Yamada
- Department of Nursing, Toho University Omori Medical Center, Tokyo, Japan
| | - Hiroyuki Yamada
- Department of Primary Care and Emergency Medicine, Kyoto University Hospital, Kyoto, Japan
| | - Ryo Yamamoto
- Department of Emergency and Critical Care Medicine, Keio University School of Medicine, Tokyo, Japan
| | - Takeshi Yoshida
- Department of Anesthesiology and Intensive Care Medicine, Osaka University Graduate School of Medicine, Suita, Japan
| | - Yuhei Yoshida
- Nursing Department, Osaka General Medical Center, Osaka, Japan
| | - Jumpei Yoshimura
- Division of Trauma and Surgical Critical Care, Osaka General Medical Center, Osaka, Japan
| | | | - Hiroshi Yonekura
- Department of Clinical Anesthesiology, Mie University Hospital, Tsu, Japan
| | - Takeshi Wada
- Department of Anesthesiology and Critical Care Medicine, Division of Acute and Critical Care Medicine, Hokkaido University Faculty of Medicine, Sapporo, Japan
| | - Eizo Watanabe
- Department of Emergency and Critical Care Medicine, Eastern Chiba Medical Center, Togane, Japan
| | - Makoto Aoki
- Department of Emergency Medicine, Gunma University Graduate School of Medicine, Maebashi, Japan
| | - Hideki Asai
- Department of Emergency and Critical Care Medicine, Nara Medical University, Kashihara, Japan
| | - Takakuni Abe
- Department of Anesthesiology and Intensive Care, Oita University Hospital, Yufu, Japan
| | - Yutaka Igarashi
- Department of Emergency and Critical Care Medicine, Nippon Medical School Hospital, Tokyo, Japan
| | - Naoya Iguchi
- Department of Anesthesiology and Intensive Care Medicine, Graduate School of Medicine, Osaka University, Suita, Japan
| | - Masami Ishikawa
- Department of Anesthesiology, Emergency and Critical Care Medicine, Kure Kyosai Hospital, Kure, Japan
| | - Go Ishimaru
- Department of General Internal Medicine, Soka Municipal Hospital, Soka, Japan
| | - Shutaro Isokawa
- Department of Emergency and Critical Care Medicine, St. Luke's International Hospital, Tokyo, Japan
| | - Ryuta Itakura
- Department of Emergency and Critical Care Medicine, Tokyo Metropolitan Children's Medical Center, Tokyo, Japan
| | - Hisashi Imahase
- Department of Biomedical Ethics, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Haruki Imura
- Department of Infectious Diseases, Rakuwakai Otowa Hospital, Kyoto, Japan
- Department of Health Informatics, School of Public Health, Kyoto University, Kyoto, Japan
| | | | - Kenji Uehara
- Department of Anesthesiology, National Hospital Organization Iwakuni Clinical Center, Iwakuni, Japan
| | - Noritaka Ushio
- Advanced Medical Emergency Department and Critical Care Center, Japan Red Cross Maebashi Hospital, Maebashi, Japan
| | - Takeshi Umegaki
- Department of Anesthesiology, Kansai Medical University, Hirakata, Japan
| | - Yuko Egawa
- Advanced Emergency and Critical Care Center, Saitama Red Cross Hospital, Saitama, Japan
| | - Yuki Enomoto
- Department of Emergency and Critical Care Medicine, University of Tsukuba, Tsukuba, Japan
| | - Kohei Ota
- Department of Emergency and Critical Care Medicine, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan
| | - Yoshifumi Ohchi
- Department of Anesthesiology and Intensive Care, Oita University Hospital, Yufu, Japan
| | - Takanori Ohno
- Department of Emergency and Critical Medicine, Showa University Fujigaoka Hospital, Yokohama, Japan
| | - Hiroyuki Ohbe
- Department of Clinical Epidemiology and Health Economics, School of Public Health, The University of Tokyo, Tokyo, Japan
| | | | - Nobunaga Okada
- Department of Emergency Medicine, Kyoto Prefectural University of Medicine, Kyoto, Japan
| | - Yohei Okada
- Department of Primary care and Emergency medicine, Kyoto University Graduate School of Medicine, Kyoto, Japan
| | - Hiromu Okano
- Department of Anesthesiology, Kyorin University School of Medicine, Tokyo, Japan
| | - Jun Okamoto
- Department of ER, Hashimoto Municipal Hospital, Hashimoto, Japan
| | - Hiroshi Okuda
- Department of Community Medical Supports, Tohoku Medical Megabank Organization, Tohoku University, Sendai, Japan
| | - Takayuki Ogura
- Tochigi prefectural Emergency and Critical Care Center, Imperial Gift Foundation Saiseikai, Utsunomiya Hospital, Utsunomiya, Japan
| | - Yu Onodera
- Department of Anesthesiology, Faculty of Medicine, Yamagata University, Yamagata, Japan
| | - Yuhta Oyama
- Department of Internal Medicine, Dialysis Center, Kichijoji Asahi Hospital, Tokyo, Japan
| | - Motoshi Kainuma
- Anesthesiology, Emergency Medicine, and Intensive Care Division, Inazawa Municipal Hospital, Inazawa, Japan
| | - Eisuke Kako
- Department of Anesthesiology and Intensive Care Medicine, Nagoya-City University Graduate School of Medical Sciences, Nagoya, Japan
| | - Masahiro Kashiura
- Department of Emergency and Critical Care Medicine, Jichi Medical University Saitama Medical Center, Saitama, Japan
| | - Hiromi Kato
- Department of Anesthesiology and Intensive Care Medicine, Hamamatsu University School of Medicine, Hamamatsu, Japan
| | - Akihiro Kanaya
- Department of Anesthesiology, Sendai Medical Center, Sendai, Japan
| | - Tadashi Kaneko
- Emergency and Critical Care Center, Mie University Hospital, Tsu, Japan
| | - Keita Kanehata
- Advanced Medical Emergency Department and Critical Care Center, Japan Red Cross Maebashi Hospital, Maebashi, Japan
| | - Ken-Ichi Kano
- Department of Emergency Medicine, Fukui Prefectural Hospital, Fukui, Japan
| | - Hiroyuki Kawano
- Department of Gastroenterological Surgery, Onga Hospital, Fukuoka, Japan
| | - Kazuya Kikutani
- Department of Emergency and Critical Care Medicine, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan
| | - Hitoshi Kikuchi
- Department of Emergency and Critical Care Medicine, Seirei Mikatahara General Hospital, Hamamatsu, Japan
| | - Takahiro Kido
- Department of Pediatrics, University of Tsukuba Hospital, Tsukuba, Japan
| | - Sho Kimura
- Division of Critical Care Medicine, Saitama Children's Medical Center, Saitama, Japan
| | - Hiroyuki Koami
- Center for Translational Injury Research, University of Texas Health Science Center at Houston, Houston, USA
| | - Daisuke Kobashi
- Advanced Medical Emergency Department and Critical Care Center, Japan Red Cross Maebashi Hospital, Maebashi, Japan
| | - Iwao Saiki
- Department of Anesthesiology, Tokyo Medical University, Tokyo, Japan
| | - Masahito Sakai
- Department of General Medicine Shintakeo Hospital, Takeo, Japan
| | - Ayaka Sakamoto
- Department of Emergency and Critical Care Medicine, University of Tsukuba Hospital, Tsukuba, Japan
| | - Tetsuya Sato
- Tohoku University Hospital Emergency Center, Sendai, Japan
| | - Yasuhiro Shiga
- Department of Orthopaedic Surgery, Center for Advanced Joint Function and Reconstructive Spine Surgery, Graduate school of Medicine, Chiba University, Chiba, Japan
| | - Manabu Shimoto
- Department of Primary care and Emergency medicine, Kyoto University Graduate School of Medicine, Kyoto, Japan
| | - Shinya Shimoyama
- Department of Pediatric Cardiology and Intensive Care, Gunma Children's Medical Center, Shibukawa, Japan
| | - Tomohisa Shoko
- Department of Emergency and Critical Care Medicine, Tokyo Women's Medical University Medical Center East, Tokyo, Japan
| | - Yoh Sugawara
- Department of Anesthesiology, Yokohama City University, Yokohama, Japan
| | - Atsunori Sugita
- Department of Acute Medicine, Division of Emergency and Critical Care Medicine, Nihon University School of Medicine, Tokyo, Japan
| | - Satoshi Suzuki
- Department of Intensive Care, Okayama University Hospital, Okayama, Japan
| | - Yuji Suzuki
- Department of Anesthesiology and Intensive Care Medicine, Hamamatsu University School of Medicine, Hamamatsu, Japan
| | - Tomohiro Suhara
- Department of Anesthesiology, Keio University School of Medicine, Tokyo, Japan
| | - Kenji Sonota
- Department of Intensive Care Medicine, Miyagi Children's Hospital, Sendai, Japan
| | - Shuhei Takauji
- Department of Emergency Medicine, Asahikawa Medical University, Asahikawa, Japan
| | - Kohei Takashima
- Critical Care Medicine, National Center for Child Health and Development, Tokyo, Japan
| | - Sho Takahashi
- Department of Cardiology, Fukuyama City Hospital, Fukuyama, Japan
| | - Yoko Takahashi
- Department of General Internal Medicine, Koga General Hospital, Koga, Japan
| | - Jun Takeshita
- Department of Anesthesiology, Osaka Women's and Children's Hospital, Izumi, Japan
| | - Yuuki Tanaka
- Fukuoka Prefectural Psychiatric Center, Dazaifu Hospital, Dazaifu, Japan
| | - Akihito Tampo
- Department of Emergency Medicine, Asahikawa Medical University, Asahikawa, Japan
| | - Taichiro Tsunoyama
- Department of Emergency Medicine, Teikyo University School of Medicine, Tokyo, Japan
| | - Kenichi Tetsuhara
- Emergency and Critical Care Center, Kyushu University Hospital, Fukuoka, Japan
| | - Kentaro Tokunaga
- Department of Intensive Care Medicine, Kumamoto University Hospital, Kumamoto, Japan
| | - Yoshihiro Tomioka
- Department of Anesthesiology and Intensive Care Unit, Todachuo General Hospital, Toda, Japan
| | - Kentaro Tomita
- Department of Pediatrics, Keio University School of Medicine, Tokyo, Japan
| | - Naoki Tominaga
- Department of Emergency and Critical Care Medicine, Nippon Medical School Hospital, Tokyo, Japan
| | - Mitsunobu Toyosaki
- Department of Emergency and Critical Care Medicine, Keio University School of Medicine, Tokyo, Japan
| | - Yukitoshi Toyoda
- Department of Emergency and Critical Care Medicine, Saiseikai Yokohamashi Tobu Hospital, Yokohama, Japan
| | - Hiromichi Naito
- Department of Emergency, Critical Care, and Disaster Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan
| | - Isao Nagata
- Intensive Care Unit, Yokohama City Minato Red Cross Hospital, Yokohama, Japan
| | - Tadashi Nagato
- Department of Respiratory Medicine, Tokyo Yamate Medical Center, Tokyo, Japan
| | - Yoshimi Nakamura
- Department of Emergency and Critical Care Medicine, Japanese Red Cross Kyoto Daini Hospital, Kyoto, Japan
| | - Yuki Nakamori
- Department of Clinical Anesthesiology, Mie University Hospital, Tsu, Japan
| | - Isao Nahara
- Department of Anesthesiology and Critical Care Medicine, Nagoya Daini Red Cross Hospital, Nagoya, Japan
| | - Hiromu Naraba
- Department of Emergency and Critical Care Medicine, Hitachi General Hospital, Hitachi, Japan
| | - Chihiro Narita
- Department of Emergency Medicine and Intensive Care Medicine, Shizuoka General Hospital, Shizuoka, Japan
| | - Norihiro Nishioka
- Department of Preventive Services, Kyoto University Graduate School of Medicine, Kyoto, Japan
| | - Tomoya Nishimura
- Advanced Medical Emergency Department and Critical Care Center, Japan Red Cross Maebashi Hospital, Maebashi, Japan
| | - Kei Nishiyama
- Division of Emergency and Critical Care Medicine Niigata University Graduate School of Medical and Dental Science, Niigata, Japan
| | - Tomohisa Nomura
- Department of Emergency and Critical Care Medicine, Juntendo University Nerima Hospital, Tokyo, Japan
| | - Taiki Haga
- Department of Pediatric Critical Care Medicine, Osaka City General Hospital, Osaka, Japan
| | - Yoshihiro Hagiwara
- Department of Emergency and Critical Care Medicine, Saiseikai Utsunomiya Hospital, Utsunomiya, Japan
| | - Katsuhiko Hashimoto
- Research Associate of Minimally Invasive Surgical and Medical Oncology, Fukushima Medical University, Fukushima, Japan
| | - Takeshi Hatachi
- Department of Intensive Care Medicine, Osaka Women's and Children's Hospital, Izumi, Japan
| | - Toshiaki Hamasaki
- Department of Emergency Medicine, Japanese Red Cross Society Wakayama Medical Center, Wakayama, Japan
| | - Takuya Hayashi
- Division of Critical Care Medicine, Saitama Children's Medical Center, Saitama, Japan
| | - Minoru Hayashi
- Department of Emergency Medicine, Fukui Prefectural Hospital, Fukui, Japan
| | - Atsuki Hayamizu
- Department of Emergency Medicine, Saitama Saiseikai Kurihashi Hospital, Kuki, Japan
| | - Go Haraguchi
- Division of Intensive Care Unit, Sakakibara Heart Institute, Tokyo, Japan
| | - Yohei Hirano
- Department of Emergency and Critical Care Medicine, Juntendo University Urayasu Hospital, Urayasu, Japan
| | - Ryo Fujii
- Department of Emergency Medicine and Critical Care Medicine, Tochigi Prefectural Emergency and Critical Care Center, Imperial Foundation Saiseikai Utsunomiya Hospital, Utsunomiya, Japan
| | - Motoki Fujita
- Acute and General Medicine, Yamaguchi University Graduate School of Medicine, Ube, Japan
| | - Naoyuki Fujimura
- Department of Anesthesiology, St. Mary's Hospital, Our Lady of the Snow Social Medical Corporation, Kurume, Japan
| | - Hiraku Funakoshi
- Department of Emergency and Critical Care Medicine, Tokyo Bay Urayasu Ichikawa Medical Center, Urayasu, Japan
| | - Masahito Horiguchi
- Department of Emergency and Critical Care Medicine, Japanese Red Cross Kyoto Daiichi Hospital, Kyoto, Japan
| | - Jun Maki
- Department of Critical Care Medicine, Kyushu University Hospital, Fukuoka, Japan
| | - Naohisa Masunaga
- Department of Healthcare Epidemiology, School of Public Health in the Graduate School of Medicine, Kyoto University, Kyoto, Japan
| | - Yosuke Matsumura
- Department of Intensive Care, Chiba Emergency Medical Center, Chiba, Japan
| | - Takuya Mayumi
- Department of Internal Medicine, Kanazawa Municipal Hospital, Kanazawa, Japan
| | - Keisuke Minami
- Ishikawa Prefectual Central Hospital Emergency and Critical Care Center, Kanazawa, Japan
| | - Yuya Miyazaki
- Department of Emergency and General Internal Medicine, Saiseikai Kawaguchi General Hospital, Kawaguchi, Japan
| | - Kazuyuki Miyamoto
- Department of Emergency and Disaster Medicine, Showa University, Tokyo, Japan
| | - Teppei Murata
- Department of Cardiology, Tokyo Metropolitan Geriatric Hospital and Institute of Gerontology, Tokyo, Japan
| | - Machi Yanai
- Department of Emergency Medicine, Kobe City Medical Center General Hospital, Kobe, Japan
| | - Takao Yano
- Department of Critical Care and Emergency Medicine, Miyazaki Prefectural Nobeoka Hospital, Nobeoka, Japan
| | - Kohei Yamada
- Department of Traumatology and Critical Care Medicine, National Defense Medical College, Tokorozawa, Japan
| | - Naoki Yamada
- Department of Emergency Medicine, University of Fukui Hospital, Fukui, Japan
| | - Tomonori Yamamoto
- Department of Intensive Care Unit, Nara Prefectural General Medical Center, Nara, Japan
| | - Shodai Yoshihiro
- Pharmaceutical Department, JA Hiroshima General Hospital, Hatsukaichi, Japan
| | - Hiroshi Tanaka
- Department of Emergency and Critical Care Medicine, Juntendo University Urayasu Hospital, Urayasu, Japan
| | - Osamu Nishida
- Department of Anesthesiology and Critical Care Medicine, Fujita Health University School of Medicine, Toyoake, Japan
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Mitaka C, Kusaoi M, Kawagoe I, Satoh D. Up-to-date information on polymyxin B-immobilized fiber column direct hemoperfusion for septic shock. Acute Crit Care 2021; 36:85-91. [PMID: 33813808 PMCID: PMC8182162 DOI: 10.4266/acc.2021.00150] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/02/2021] [Accepted: 03/03/2021] [Indexed: 11/30/2022] Open
Abstract
Endotoxin adsorption therapy by polymyxin B-immobilized fiber column direct hemoperfusion (PMX-DHP) has been used for the treatment of septic shock patients. Endotoxin, an outer membrane component of Gram-negative bacteria, plays an important role in the pathogenesis of septic shock. Endotoxin triggers a signaling cascade for leukocytes, macrophage, and endothelial cells to secrete various mediators including cytokines and nitric oxide, leading to septic shock and multiple organ dysfunction syndrome. PMX-DHP directly adsorbed not only endotoxin but also monocytes and anandamide. It reduced blood levels of inflammatory cytokines such as interleukin (IL)-1, IL-6, tumor necrosis factor-alpha and IL-17A, adhesion molecules, plasminogen activator inhibitor 1, and high mobility group box-1. As a result, PMX-DHP increased blood pressure and reduced the dose of vasoactive-inotropic agents. PMX-DHP improved monocyte human leukocyte antigen-DR expression in patients with severe sepsis and septic shock. A post hoc analysis of EUPHRATES (Evaluating the Use of Polymyxin B Hemoperfusion in Randomized Controlled Trial of Adults Treated for Endotoxemia and Septic Shock) trial has shown that PMX-DHP significantly reduced 28-day mortality compared with the control group in septic shock patients with endotoxin activity assay level between 0.60 and 0.89. Longer duration of PMX-DHP may be another strategy to bring out the beneficial effects of PMX-DHP. Further studies are needed to confirm the efficacy of PMX-DHP treatment for septic shock.
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Affiliation(s)
- Chieko Mitaka
- Department of Anesthesiology and Pain Medicine, Juntendo University Faculty of Medicine, Tokyo, Japan
| | - Makio Kusaoi
- Department of Internal Medicine and Rheumatology, Juntendo University Faculty of Medicine, Tokyo, Japan
| | - Izumi Kawagoe
- Department of Anesthesiology and Pain Medicine, Juntendo University Faculty of Medicine, Tokyo, Japan
| | - Daizoh Satoh
- Department of Anesthesiology and Pain Medicine, Juntendo University Faculty of Medicine, Tokyo, Japan
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Egi M, Ogura H, Yatabe T, Atagi K, Inoue S, Iba T, Kakihana Y, Kawasaki T, Kushimoto S, Kuroda Y, Kotani J, Shime N, Taniguchi T, Tsuruta R, Doi K, Doi M, Nakada T, Nakane M, Fujishima S, Hosokawa N, Masuda Y, Matsushima A, Matsuda N, Yamakawa K, Hara Y, Sakuraya M, Ohshimo S, Aoki Y, Inada M, Umemura Y, Kawai Y, Kondo Y, Saito H, Taito S, Takeda C, Terayama T, Tohira H, Hashimoto H, Hayashida K, Hifumi T, Hirose T, Fukuda T, Fujii T, Miura S, Yasuda H, Abe T, Andoh K, Iida Y, Ishihara T, Ide K, Ito K, Ito Y, Inata Y, Utsunomiya A, Unoki T, Endo K, Ouchi A, Ozaki M, Ono S, Katsura M, Kawaguchi A, Kawamura Y, Kudo D, Kubo K, Kurahashi K, Sakuramoto H, Shimoyama A, Suzuki T, Sekine S, Sekino M, Takahashi N, Takahashi S, Takahashi H, Tagami T, Tajima G, Tatsumi H, Tani M, Tsuchiya A, Tsutsumi Y, Naito T, Nagae M, Nagasawa I, Nakamura K, Nishimura T, Nunomiya S, Norisue Y, Hashimoto S, Hasegawa D, Hatakeyama J, Hara N, Higashibeppu N, Furushima N, Furusono H, Matsuishi Y, Matsuyama T, Minematsu Y, Miyashita R, Miyatake Y, Moriyasu M, Yamada T, et alEgi M, Ogura H, Yatabe T, Atagi K, Inoue S, Iba T, Kakihana Y, Kawasaki T, Kushimoto S, Kuroda Y, Kotani J, Shime N, Taniguchi T, Tsuruta R, Doi K, Doi M, Nakada T, Nakane M, Fujishima S, Hosokawa N, Masuda Y, Matsushima A, Matsuda N, Yamakawa K, Hara Y, Sakuraya M, Ohshimo S, Aoki Y, Inada M, Umemura Y, Kawai Y, Kondo Y, Saito H, Taito S, Takeda C, Terayama T, Tohira H, Hashimoto H, Hayashida K, Hifumi T, Hirose T, Fukuda T, Fujii T, Miura S, Yasuda H, Abe T, Andoh K, Iida Y, Ishihara T, Ide K, Ito K, Ito Y, Inata Y, Utsunomiya A, Unoki T, Endo K, Ouchi A, Ozaki M, Ono S, Katsura M, Kawaguchi A, Kawamura Y, Kudo D, Kubo K, Kurahashi K, Sakuramoto H, Shimoyama A, Suzuki T, Sekine S, Sekino M, Takahashi N, Takahashi S, Takahashi H, Tagami T, Tajima G, Tatsumi H, Tani M, Tsuchiya A, Tsutsumi Y, Naito T, Nagae M, Nagasawa I, Nakamura K, Nishimura T, Nunomiya S, Norisue Y, Hashimoto S, Hasegawa D, Hatakeyama J, Hara N, Higashibeppu N, Furushima N, Furusono H, Matsuishi Y, Matsuyama T, Minematsu Y, Miyashita R, Miyatake Y, Moriyasu M, Yamada T, Yamada H, Yamamoto R, Yoshida T, Yoshida Y, Yoshimura J, Yotsumoto R, Yonekura H, Wada T, Watanabe E, Aoki M, Asai H, Abe T, Igarashi Y, Iguchi N, Ishikawa M, Ishimaru G, Isokawa S, Itakura R, Imahase H, Imura H, Irinoda T, Uehara K, Ushio N, Umegaki T, Egawa Y, Enomoto Y, Ota K, Ohchi Y, Ohno T, Ohbe H, Oka K, Okada N, Okada Y, Okano H, Okamoto J, Okuda H, Ogura T, Onodera Y, Oyama Y, Kainuma M, Kako E, Kashiura M, Kato H, Kanaya A, Kaneko T, Kanehata K, Kano K, Kawano H, Kikutani K, Kikuchi H, Kido T, Kimura S, Koami H, Kobashi D, Saiki I, Sakai M, Sakamoto A, Sato T, Shiga Y, Shimoto M, Shimoyama S, Shoko T, Sugawara Y, Sugita A, Suzuki S, Suzuki Y, Suhara T, Sonota K, Takauji S, Takashima K, Takahashi S, Takahashi Y, Takeshita J, Tanaka Y, Tampo A, Tsunoyama T, Tetsuhara K, Tokunaga K, Tomioka Y, Tomita K, Tominaga N, Toyosaki M, Toyoda Y, Naito H, Nagata I, Nagato T, Nakamura Y, Nakamori Y, Nahara I, Naraba H, Narita C, Nishioka N, Nishimura T, Nishiyama K, Nomura T, Haga T, Hagiwara Y, Hashimoto K, Hatachi T, Hamasaki T, Hayashi T, Hayashi M, Hayamizu A, Haraguchi G, Hirano Y, Fujii R, Fujita M, Fujimura N, Funakoshi H, Horiguchi M, Maki J, Masunaga N, Matsumura Y, Mayumi T, Minami K, Miyazaki Y, Miyamoto K, Murata T, Yanai M, Yano T, Yamada K, Yamada N, Yamamoto T, Yoshihiro S, Tanaka H, Nishida O. The Japanese Clinical Practice Guidelines for Management of Sepsis and Septic Shock 2020 (J-SSCG 2020). Acute Med Surg 2021; 8:e659. [PMID: 34484801 PMCID: PMC8390911 DOI: 10.1002/ams2.659] [Show More Authors] [Citation(s) in RCA: 40] [Impact Index Per Article: 10.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022] Open
Abstract
The Japanese Clinical Practice Guidelines for Management of Sepsis and Septic Shock 2020 (J-SSCG 2020), a Japanese-specific set of clinical practice guidelines for sepsis and septic shock created as revised from J-SSCG 2016 jointly by the Japanese Society of Intensive Care Medicine and the Japanese Association for Acute Medicine, was first released in September 2020 and published in February 2021. An English-language version of these guidelines was created based on the contents of the original Japanese-language version. The purpose of this guideline is to assist medical staff in making appropriate decisions to improve the prognosis of patients undergoing treatment for sepsis and septic shock. We aimed to provide high-quality guidelines that are easy to use and understand for specialists, general clinicians, and multidisciplinary medical professionals. J-SSCG 2016 took up new subjects that were not present in SSCG 2016 (e.g., ICU-acquired weakness [ICU-AW], post-intensive care syndrome [PICS], and body temperature management). The J-SSCG 2020 covered a total of 22 areas with four additional new areas (patient- and family-centered care, sepsis treatment system, neuro-intensive treatment, and stress ulcers). A total of 118 important clinical issues (clinical questions, CQs) were extracted regardless of the presence or absence of evidence. These CQs also include those that have been given particular focus within Japan. This is a large-scale guideline covering multiple fields; thus, in addition to the 25 committee members, we had the participation and support of a total of 226 members who are professionals (physicians, nurses, physiotherapists, clinical engineers, and pharmacists) and medical workers with a history of sepsis or critical illness. The GRADE method was adopted for making recommendations, and the modified Delphi method was used to determine recommendations by voting from all committee members. As a result, 79 GRADE-based recommendations, 5 Good Practice Statements (GPS), 18 expert consensuses, 27 answers to background questions (BQs), and summaries of definitions and diagnosis of sepsis were created as responses to 118 CQs. We also incorporated visual information for each CQ according to the time course of treatment, and we will also distribute this as an app. The J-SSCG 2020 is expected to be widely used as a useful bedside guideline in the field of sepsis treatment both in Japan and overseas involving multiple disciplines.
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Snow TAC, Littlewood S, Corredor C, Singer M, Arulkumaran N. Effect of Extracorporeal Blood Purification on Mortality in Sepsis: A Meta-Analysis and Trial Sequential Analysis. Blood Purif 2020; 50:462-472. [PMID: 33113533 DOI: 10.1159/000510982] [Citation(s) in RCA: 16] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/30/2020] [Accepted: 08/16/2020] [Indexed: 11/19/2022]
Abstract
OBJECTIVE The objective of this study was to conduct a meta-analysis and trial sequential analysis (TSA) of published randomized controlled trials (RCTs) to determine whether mortality benefit exists for extracorporeal blood purification techniques in sepsis. DATA SOURCES A systematic search on MEDLINE, Embase, and the Cochrane Central Register of Controlled Trials for RCTs was performed. STUDY SELECTION RCTs investigating the effect of extracorporeal blood purification device use on mortality among critically ill septic patients were selected. DATA EXTRACTION Mortality was assessed using Mantel-Haenszel models, and I2 was used for heterogeneity. Data are presented as odds ratios (OR); 95% confidence intervals (CIs); p values; I2. Using the control event mortality proportion, we performed a TSA and calculated the required information size using an anticipated intervention effect of a 14% relative reduction in mortality. DATA SYNTHESIS Thirty-nine RCTs were identified, with 2,729 patients. Fourteen studies used hemofiltration (n = 789), 17 used endotoxin adsorption devices (n = 1,363), 3 used nonspecific adsorption (n = 110), 2 were cytokine removal devices (n = 117), 2 used coupled plasma filtration adsorption (CPFA) (n = 207), 2 combined hemofiltration and perfusion (n = 40), and 1 used plasma exchange (n = 106). On conventional meta-analysis, hemofiltration (OR 0.56 [0.40-0.79]; p < 0.001; I2 = 0%), endotoxin removal devices (OR 0.40 [0.23-0.67], p < 0.001; I2 = 71%), and nonspecific adsorption devices (OR 0.32 [0.13-0.82]; p = 0.02; I2 = 23%) were associated with mortality benefit, but not cytokine removal (OR 0.99 [0.07-13.42], p = 0.99; I2 = 64%), CPFA (OR 0.50 [0.10-2.47]; p = 0.40; I2 = 64%), or combined hemofiltration and adsorption (OR 0.71 [0.13-3.79]; p = 0.69; I2 = 0%). TSA however revealed that based on the number of existing patients recruited for RCTs, neither hemofiltration (TSA-adjusted CI 0.29-1.10), endotoxin removal devices (CI 0.05-3.40), nor nonspecific adsorption devices (CI 0.01-14.31) were associated with mortality benefit. CONCLUSION There are inadequate data at present to conclude that the use of extracorporeal blood purification techniques in sepsis is beneficial. Further adequately powered RCTs are required to confirm any potential mortality benefit, which may be most evident in patients at greatest risk of death.
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Affiliation(s)
- Timothy A C Snow
- Bloomsbury Institute of Intensive Care Medicine, University College London, London, United Kingdom,
| | | | - Carlos Corredor
- Department of Perioperative Medicine, St Bartholomew's Hospital, London, United Kingdom
| | - Mervyn Singer
- Bloomsbury Institute of Intensive Care Medicine, University College London, London, United Kingdom
| | - Nishkantha Arulkumaran
- Bloomsbury Institute of Intensive Care Medicine, University College London, London, United Kingdom
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Li X, Liu C, Mao Z, Qi S, Song R, Zhou F. Effectiveness of polymyxin B-immobilized hemoperfusion against sepsis and septic shock: A systematic review and meta-analysis. J Crit Care 2020; 63:187-195. [PMID: 33012579 DOI: 10.1016/j.jcrc.2020.09.007] [Citation(s) in RCA: 21] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/03/2020] [Revised: 09/01/2020] [Accepted: 09/07/2020] [Indexed: 12/18/2022]
Abstract
PURPOSE To evaluate the efficacy and safety of Polymyxin B-immobilized hemoperfusion (PMX-HP) against sepsis or septic shock. METHODS We searched databases (PubMed, EMBASE and Cochrane Library) to identify eligible randomized controlled trials (RCTs). The primary outcomes we included in this review were mortality at the longest follow-up available and serious adverse events associated with treatments. We used the Cochrane risk of bias assessment tool to evaluate risk of bias. Trial Sequential Analysis (TSA) was performed to assess the conclusion reached in our research. RESULTS Thirteen studies including 1163 patients were identified. Use of PMX-HP could reduce overall mortality [relative risk (RR) 0.68, 95% confidence interval (CI) 0.51-0.91, P = 0.01]. An interesting finding was that the mortality of patients in Acute Physiology and Chronic Health Evaluation (APACHE II) scores <25 group (RR 0.64, 95% CI 0.52-0.78, P < 0.0001) and sepsis group (RR 0.48, 95% CI 0.32-0.72, P = 0.0003) significantly decreased after PMX-HP treatment. The result also showed that PMX-HP could reduce endotoxin levels [Standardized mean difference (SMD) -1.53, 95% CI -2.92- -0.13, P = 0.03] and improve mean arterial pressure (SMD 1.07, 95% CI 0.14-2.01, P = 0.02). Serious adverse events between the PMX-HP group and standard therapy group were not significantly different (RR 2.16, 95% CI 0.97-4.80, I2 = 0%, P = 0.06). However, TSA did not provide conclusive evidence and more high quality RCTs were required. CONCLUSION Using PMX-HP to treat patients with less severe sepsis can reduce overall mortality and is safe. Treatment efficacy may benefit from the reduction of endotoxin level and the improvement of hemodynamics. More high quality RCTs are required to further evaluate the clinical role of PMX-HP against severe sepsis or septic shock.
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Affiliation(s)
- Xiaoming Li
- Department of Critical Care Medicine, the first Medical Centre, Chinese PLA General Hospital, People's Republic of China; Medical School of Chinese PLA, People's Republic of China
| | - Chao Liu
- Medical School of Chinese PLA, People's Republic of China; Department of Critical Care Medicine, the first Medical Centre, Chinese PLA General Hospital, People's Republic of China
| | - Zhi Mao
- Department of Critical Care Medicine, the first Medical Centre, Chinese PLA General Hospital, People's Republic of China
| | - Shuang Qi
- Department of Critical Care Medicine, the first Medical Centre, Chinese PLA General Hospital, People's Republic of China; Medical School of Chinese PLA, People's Republic of China
| | - Renjie Song
- Department of Critical Care Medicine, the first Medical Centre, Chinese PLA General Hospital, People's Republic of China; Medical School of Chinese PLA, People's Republic of China
| | - Feihu Zhou
- Department of Critical Care Medicine, the first Medical Centre, Chinese PLA General Hospital, People's Republic of China.
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10
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Effect of polymyxin B hemoperfusion on the outcome of patients with sepsis and septic shock. J Infect 2020; 80:350-371. [DOI: 10.1016/j.jinf.2019.11.013] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/17/2019] [Accepted: 11/20/2019] [Indexed: 11/15/2022]
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11
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Blood Purification and Mortality in Sepsis and Septic Shock: A Systematic Review and Meta-analysis of Randomized Trials. Anesthesiology 2020; 131:580-593. [PMID: 31246600 DOI: 10.1097/aln.0000000000002820] [Citation(s) in RCA: 37] [Impact Index Per Article: 7.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/02/2023]
Abstract
BACKGROUND Sepsis and septic shock are severe inflammatory conditions related to high morbidity and mortality. We performed a systematic review with meta-analysis of randomized trials to assess whether extracorporeal blood purification reduces mortality in this setting. METHODS Electronic databases were searched for pertinent studies up to January 2019. We included randomized controlled trials on the use of hemoperfusion, hemofiltration without a renal replacement purpose, and plasmapheresis as a blood purification technique in comparison to conventional therapy in adult patients with sepsis and septic shock. The primary outcome was mortality at the longest follow-up available. We calculated relative risks and 95% CIs. The grading of recommendations assessment, development and evaluation methodology for the certainty of evidence was used. RESULTS Thirty-seven trials with 2,499 patients were included in the meta-analysis. Hemoperfusion was associated with lower mortality compared to conventional therapy (relative risk = 0.88 [95% CI, 0.78 to 0.98], P = 0.02, very low certainty evidence). Low risk of bias trials on polymyxin B immobilized filter hemoperfusion showed no mortality difference versus control (relative risk = 1.14 [95% CI, 0.96 to 1.36], P = 0.12, moderate certainty evidence), while recent trials found an increased mortality (relative risk = 1.22 [95% CI, 1.03 to 1.45], P = 0.02, low certainty evidence); trials performed in the United States and Europe had no significant difference in mortality (relative risk = 1.13 [95% CI, 0.96 to 1.34], P = 0.15), while trials performed in Asia had a positive treatment effect (relative risk = 0.57 [95% CI, 0.47 to 0.69], P < 0.001). Hemofiltration (relative risk = 0.79 [95% CI, 0.63 to 1.00], P = 0.05, very low certainty evidence) and plasmapheresis (relative risk = 0.63 [95% CI, 0.42 to 0.96], P = 0.03, very low certainty evidence) were associated with a lower mortality. CONCLUSIONS Very low-quality randomized evidence demonstrates that the use of hemoperfusion, hemofiltration, or plasmapheresis may reduce mortality in sepsis or septic shock. Existing evidence of moderate quality and certainty does not provide any support for a difference in mortality using polymyxin B hemoperfusion. Further high-quality randomized trials are needed before systematic implementation of these therapies in clinical practice.
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Kim JJ, Park YJ, Moon KY, Park JH, Jeong YK, Kim EY. Polymyxin B hemoperfusion as a feasible therapy after source control in abdominal septic shock. World J Gastrointest Surg 2019; 11:422-432. [PMID: 31879534 PMCID: PMC6912072 DOI: 10.4240/wjgs.v11.i12.422] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/19/2019] [Revised: 10/08/2019] [Accepted: 11/21/2019] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Polymyxin B hemoperfusion (PMX-HP) has been used as a treatment for intra-abdominal septic shock by absorbing and removing endotoxins of gram-negative bacilli.
AIM To investigate the clinical efficacy of PMX-HP in patients with gram-negative septic shock who underwent abdominal surgery.
METHODS From January 2012 to December 2018, patients who had septic shock secondary to peritonitis were enrolled. They were classified into PMX-HP treated and control groups based on postopreative intervention using PMX-HP. The clinical outcomes were compared using 1:1 propensity score matching methods to balance the overall distribution between the two groups.
RESULTS After propensity score matching, 40 patients were analyzed (20 patients in the PMX group and 20 patients in the control group). The scores of total Sequential Organ Failure Assessment (SOFA) score, renal SOFA and coagulation SOFA were significantly improved in the PMX group but not in the control group. (from 11.2 ± 5.8 to 4.7 ± 3.5 in PMX group vs 10.0 ± 4.0 to 8.7 ± 7.3 in control group, P = 0.047 from 2.6 ± 1.0 to 0.7 ± 1.0 in PMX group vs 2.6 ± 1.5 to 2.8 ± 1.6 in control group, P = 0.000, from 1.6 ± 1.5 to 1.3 ± 1.3 in PMX group vs 1.2 ± 1.2 to 2.8 ± 1.8 in control group, P = 0.014, respectively). Further, the length of intensive care unit (ICU) stay was significantly shorter in PMX group. However, no statistically significant difference was found in ICU mortality (50% in PMX group vs 50% in control group).
CONCLUSION PMX-HP is a feasible adjunct treatment for peritonitis in ICU patients with peritonitis for improved organ impairment and to stabilize hemodynamics. It would be helpful to enhance clinical outcomes especially in patients with complete elimination of the source of gram-negative bacilli infection by surgical procedure accompanied with conventional treatment of sepsis.
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Affiliation(s)
- Jin Joo Kim
- Division of Trauma and Surgical Critical Care, Department of Surgery, Seoul St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul 137-701, South Korea
| | - Young Jun Park
- Department of Surgery, Seoul St. Mary’s Hospital, Seoul 137-701, South Korea
| | - Ki Yoon Moon
- Department of Surgery, Seoul St. Mary’s Hospital, Seoul 137-701, South Korea
| | - Jin Hyeong Park
- Department of Surgery, Seoul St. Mary’s Hospital, Seoul 137-701, South Korea
| | - Yong Ki Jeong
- Department of Surgery, Seoul St. Mary’s Hospital, Seoul 137-701, South Korea
| | - Eun Young Kim
- Division of Trauma and Surgical Critical Care, Department of Surgery, Seoul St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul 137-701, South Korea
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Kuriyama A, Katsura M, Urushidani S, Takada T. Impact of polymyxin B hemoperfusion in the treatment of patients with sepsis and septic shock: a meta-analysis of randomized controlled trials. ANNALS OF TRANSLATIONAL MEDICINE 2018; 6:206. [PMID: 30023369 DOI: 10.21037/atm.2018.05.41] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/01/2023]
Abstract
Background Polymyxin B hemoperfusion is a strategy to remove circulating endotoxin in patients with sepsis. Previous systematic reviews derived from randomized and non-randomized studies suggested that use of polymyxin B hemoperfusion reduced mortality, based on the pooled data from various time points in the clinical course of sepsis. We conducted a meta-analysis of randomized controlled trials to assess the impact of polymyxin B hemoperfusion specifically on 28-day mortality in patients with sepsis and septic shock. Methods PubMed, EMBASE, and the Cochrane Central Register of Controlled Trials were searched for eligible trials from inception through July 30, 2017. All randomized controlled trials were eligible if they examined the impact of polymyxin B hemoperfusion on 28-day mortality in patients with sepsis and septic shock. Risk of bias was evaluated with the Cochrane risk of bias assessment tool. Data were pooled using the DerSimonian and Laird random-effects model. Results Seven trials involving 586 participants were identified for the analysis. Use of polymyxin B hemoperfusion was not associated with a reduced risk of 28-day mortality [risk ratio (RR), 0.76; 95% CI, 0.54-1.07] compared with usual care. One unpublished trial also showed no significant 28-day survival benefit. Conclusions There is no evidence to support the use of polymyxin B hemoperfusion for patients with sepsis and septic shock with respect to 28-day mortality.
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Affiliation(s)
- Akira Kuriyama
- Emergency and Critical Care Center, Kurashiki Central Hospital, Okayama, Japan
| | - Morihiro Katsura
- Department of Surgery, Okinawa Prefectural Miyako Hospital, Okinawa, Japan
| | - Seigo Urushidani
- Emergency and Critical Care Center, Kurashiki Central Hospital, Okayama, Japan
| | - Tadaaki Takada
- Department of Emergency Medicine, Tokushima Red Cross Hospital, Tokushima, Japan
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Corrigendum to “Effects of polymyxin B hemoperfusion on hemodynamics and prognosis in septic shock patients” [J Crit Care 43 (2018) 202–206]. J Crit Care 2018. [DOI: 10.1016/j.jcrc.2017.04.046] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/23/2022]
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Maekawa H, Negishi K. Extended Sessions of Polymyxin-B Immobilized Fiber Column Hemoperfusion Ameliorate Renal Outcome and Mortality in Septic Shock with Acute Kidney Injury. Blood Purif 2018; 46:81-89. [DOI: 10.1159/000488639] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/18/2017] [Accepted: 03/19/2018] [Indexed: 12/21/2022]
Abstract
Background/Aims: Polymyxin-B (PMX) treatment has been reported to decrease mortality in patients with septic shock and acute kidney injury (AKI). In this study, we aimed to evaluate whether extended sessions of PMX (Ext-PMX) immobilized fiber column hemoperfusion ameliorate clinical outcomes in patients complicated with septic shock and AKI without surgical control. Methods: Twenty-two patients with nonsurgical septic shock and AKI who received PMX were included. They were divided according to the duration of PMX treatment: Ext-PMX and standard PMX (Std-PMX). Results: The mean blood pressure increased and inotrope requirement decreased within 24 h after PMX initiation. The median value of predicted mortality was 52.5%, and the 28-day mortalities in the Ext-PMX and Std-PMX groups were 44.4 and 75% respectively. Renal replacement therapy (RRT) was also initiated in 17 patients, and renal insufficiency was recovered. Conclusion: Ext-PMX combined with RRT improved clinical outcomes in patients with nonsurgical septic shock and AKI.
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Pota V, Passavanti MB, Sansone P, Pace MC, Peluso F, Fiorelli A, Aurilio C. Septic shock from descending necrotizing mediastinitis - combined treatment with IgM-enriched immunoglobulin preparation and direct polymyxin B hemoperfusion: a case report. J Med Case Rep 2018; 12:55. [PMID: 29499757 PMCID: PMC5834850 DOI: 10.1186/s13256-018-1611-5] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/13/2017] [Accepted: 02/08/2018] [Indexed: 11/14/2022] Open
Abstract
BACKGROUND Descending necrotizing mediastinitis is a common and progressive polymicrobial infection involving the neck and chest with a high death rate (10 to 40%). From a microbiological point of view, descending necrotizing mediastinitis is sustained by Gram-positive bacteria (43-62%), anaerobes (46-78%), and, rarely, Gram-negative bacteria. Data collected during the Antibiotic Resistance-Istituto Superiore di Sanità project confirmed that Italy is positioned among the countries with the highest levels of resistance in most pathogenic species under surveillance. In particular, 32.9% of Klebsiella pneumoniae isolates were resistant to carbapenem, 33.6% of Staphylococcus aureus to methicillin, and 28.7% and 43.9% of Escherichia coli isolates to third-generation cephalosporins and fluoroquinolones, respectively. CASE PRESENTATION We describe the case of a 38-year-old white man with septic shock due to descending necrotizing mediastinitis sustained by multidrug-resistant Gram-negative and Gram-positive bacteria treated after surgery with an IgM-enriched immunoglobulin preparation and polymyxin B hemoperfusion therapy. CONCLUSION Despite the contrasting data on the use of immunoglobulins and polymyxin B hemoperfusion in septic shock and the lack of literature in cases of acute mediastinitis caused by both Gram-negative and Gram-positive multidrug-resistant bacteria, we obtained an improvement in clinical conditions and the survival of our patient, against all odds.
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Affiliation(s)
- Vincenzo Pota
- Department of Women, Infant and Surgical and Specialist Surgery, University of Campania “L. Vanvitelli”, Piazza Miraglia 2, 80138 Naples, Italy
| | - Maria Beatrice Passavanti
- Department of Women, Infant and Surgical and Specialist Surgery, University of Campania “L. Vanvitelli”, Piazza Miraglia 2, 80138 Naples, Italy
| | - Pasquale Sansone
- Department of Women, Infant and Surgical and Specialist Surgery, University of Campania “L. Vanvitelli”, Piazza Miraglia 2, 80138 Naples, Italy
| | - Maria Caterina Pace
- Department of Women, Infant and Surgical and Specialist Surgery, University of Campania “L. Vanvitelli”, Piazza Miraglia 2, 80138 Naples, Italy
| | - Filomena Peluso
- Department of Women, Infant and Surgical and Specialist Surgery, University of Campania “L. Vanvitelli”, Piazza Miraglia 2, 80138 Naples, Italy
| | - Alfonso Fiorelli
- Thoracic Surgery Unit, University of Campania “L. Vanvitelli”, Naples, Italy
| | - Caterina Aurilio
- Department of Women, Infant and Surgical and Specialist Surgery, University of Campania “L. Vanvitelli”, Piazza Miraglia 2, 80138 Naples, Italy
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Schädler D, Pausch C, Heise D, Meier-Hellmann A, Brederlau J, Weiler N, Marx G, Putensen C, Spies C, Jörres A, Quintel M, Engel C, Kellum JA, Kuhlmann MK. The effect of a novel extracorporeal cytokine hemoadsorption device on IL-6 elimination in septic patients: A randomized controlled trial. PLoS One 2017; 12:e0187015. [PMID: 29084247 PMCID: PMC5662220 DOI: 10.1371/journal.pone.0187015] [Citation(s) in RCA: 236] [Impact Index Per Article: 29.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/11/2017] [Accepted: 10/10/2017] [Indexed: 12/16/2022] Open
Abstract
Objective We report on the effect of hemoadsorption therapy to reduce cytokines in septic patients with respiratory failure. Methods This was a randomized, controlled, open-label, multicenter trial. Mechanically ventilated patients with severe sepsis or septic shock and acute lung injury or acute respiratory distress syndrome were eligible for study inclusion. Patients were randomly assigned to either therapy with CytoSorb hemoperfusion for 6 hours per day for up to 7 consecutive days (treatment), or no hemoperfusion (control). Primary outcome was change in normalized IL-6-serum concentrations during study day 1 and 7. Results 97 of the 100 randomized patients were analyzed. We were not able to detect differences in systemic plasma IL-6 levels between the two groups (n = 75; p = 0.15). Significant IL-6 elimination, averaging between 5 and 18% per blood pass throughout the entire treatment period was recorded. In the unadjusted analysis, 60-day-mortality was significantly higher in the treatment group (44.7%) compared to the control group (26.0%; p = 0.039). The proportion of patients receiving renal replacement therapy at the time of enrollment was higher in the treatment group (31.9%) when compared to the control group (16.3%). After adjustment for patient morbidity and baseline imbalances, no association of hemoperfusion with mortality was found (p = 0.19). Conclusions In this patient population with predominantly septic shock and multiple organ failure, hemoadsorption removed IL-6 but this did not lead to lower plasma IL-6-levels. We did not detect statistically significant differences in the secondary outcomes multiple organ dysfunction score, ventilation time and time course of oxygenation.
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Affiliation(s)
- Dirk Schädler
- Department of Anesthesiology and Intensive Care Medicine, University Medical Center Schleswig-Holstein, Campus Kiel, Kiel, Germany
- * E-mail:
| | - Christine Pausch
- Institute for Medical Informatics, Statistics and Epidemiology, University of Leipzig, Leipzig, Germany
| | - Daniel Heise
- Centre of Anaesthesiology, Emergency and Intensive Care Medicine, University Hospital Göttingen, Göttingen, Germany
| | - Andreas Meier-Hellmann
- Department of Anesthesiology and Intensive Care Medicine, HELIOS Klinikum, Erfurt, Germany
| | - Jörg Brederlau
- Department of Intensive Care Medicine, Helios Hospital Berlin-Buch, Berlin, Germany
| | - Norbert Weiler
- Department of Anesthesiology and Intensive Care Medicine, University Medical Center Schleswig-Holstein, Campus Kiel, Kiel, Germany
| | - Gernot Marx
- Department of Intensive Care and Intermediate Care, RWTH University Hospital Aachen, Aachen, Germany
| | - Christian Putensen
- Department of Anesthesiology and Intensive Care Medicine, University of Bonn, Bonn, Germany
| | - Claudia Spies
- Anaesthesiology and Intensive Care Medicine, Campus Charité Mitte and Campus Charité Virchow-Klinikum, Charité - University Medicine Berlin, Berlin, Germany
| | - Achim Jörres
- Department of Medicine I - Nephrology, Transplantation & Medical Intensive Care, University Witten/Herdecke, Medical Center Cologne-Merheim, Cologne, Germany
| | - Michael Quintel
- Centre of Anaesthesiology, Emergency and Intensive Care Medicine, University Hospital Göttingen, Göttingen, Germany
| | - Christoph Engel
- Institute for Medical Informatics, Statistics and Epidemiology, University of Leipzig, Leipzig, Germany
| | - John A. Kellum
- Department of Critical Care Medicine, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, United States of America
| | - Martin K. Kuhlmann
- Department of Nephrology, Vivantes Klinikum im Friedrichshain, Berlin, Germany
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Lee CT, Tu YK, Yeh YC, Chang T, Shih PY, Chao A, Huang HH, Cheng YJ, Yeh YC. Effects of polymyxin B hemoperfusion on hemodynamics and prognosis in septic shock patients. J Crit Care 2017; 43:202-206. [PMID: 28915395 DOI: 10.1016/j.jcrc.2017.04.035] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/18/2017] [Revised: 03/05/2017] [Accepted: 04/22/2017] [Indexed: 01/15/2023]
Abstract
PURPOSE We designed this study to examine the clinical effects of polymyxin B hemoperfusion (PMX-HP) in septic shock patients. MATERIAL AND METHODS We retrospectively examined the effects of PMX-HP in septic shock patients with intra-abdominal or gram-negative bacterial infection during October 2013-May 2016. A one-to-one matching between the PMX-HP and conventional groups was performed, and 28-day mortality, and change in inotropic score, Sequential Organ Failure Assessment (SOFA) score, and Acute Physiology and Chronic Health Evaluation II (APACHE II) score at 24h in the two groups were compared. In addition, multivariable regression analysis and Cox proportional hazards regression model were applied in all eligible patients. RESULTS Sixty-nine patients were eligible, of whom fifty patients were enrolled for matched cohort analysis. In matched cohort analysis, change in inotropic score after 24h (-24.8 [19.7] vs. -6.4 [20.0], p=0.002) differed significantly between the PMX-HP and conventional groups. Multivariable regression analysis revealed that PMX-HP was associated with lower 28-day mortality (odds ratio 0.18, 95% CI 0.04-0.92, p=0.039) and greater improvement in inotropic and APACHE II scores. CONCLUSIONS PMX-HP may have potential benefits for hemodynamic and prognostic outcomes in septic shock patients with intra-abdominal or gram-negative bacterial infection.
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Affiliation(s)
- Chen-Tse Lee
- Department of Anesthesiology, National Taiwan University Hospital, No. 7, Chung-Shan S. Road, Taipei, Taiwan, ROC
| | - Yu-Kang Tu
- Department of Public Health, Institute of Epidemiology & Preventive Medicine, National Taiwan University, No.17, Xu-Zhou Road, Taipei, Taiwan, ROC.
| | - Yi-Chun Yeh
- Department of Public Health, Institute of Epidemiology & Preventive Medicine, National Taiwan University, No.17, Xu-Zhou Road, Taipei, Taiwan, ROC.
| | - Tzu Chang
- Department of Anesthesiology, National Taiwan University Hospital, No. 7, Chung-Shan S. Road, Taipei, Taiwan, ROC
| | - Po-Yuan Shih
- Department of Anesthesiology, National Taiwan University Hospital, No. 7, Chung-Shan S. Road, Taipei, Taiwan, ROC
| | - Anne Chao
- Department of Anesthesiology, National Taiwan University Hospital, No. 7, Chung-Shan S. Road, Taipei, Taiwan, ROC
| | - Hsing-Hao Huang
- Department of Anesthesiology, National Taiwan University Hospital, No. 7, Chung-Shan S. Road, Taipei, Taiwan, ROC.
| | - Ya-Jung Cheng
- Department of Anesthesiology, National Taiwan University Hospital, No. 7, Chung-Shan S. Road, Taipei, Taiwan, ROC.
| | - Yu-Chang Yeh
- Department of Anesthesiology, National Taiwan University Hospital, No. 7, Chung-Shan S. Road, Taipei, Taiwan, ROC.
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Terayama T, Yamakawa K, Umemura Y, Aihara M, Fujimi S. Polymyxin B Hemoperfusion for Sepsis and Septic Shock: A Systematic Review and Meta-Analysis. Surg Infect (Larchmt) 2017; 18:225-233. [PMID: 28092497 DOI: 10.1089/sur.2016.168] [Citation(s) in RCA: 30] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022] Open
Abstract
BACKGROUND To evaluate the efficacy and safety of direct hemoperfusion with polymyxin B-immobilized fiber (PMX-DHP) therapy in patients with sepsis. DESIGN A systematic review and meta-analysis of four major databases: Cochrane Central Register of Controlled Trials, MEDLINE, Scopus, and Science Citation Index Expanded. STUDY SELECTION Randomized controlled trials comparing PMX-DHP with conventional therapy on the outcome of mortality in patients with severe sepsis/septic shock. DATA EXTRACTION Two reviewers independently applied eligibility criteria, assessed quality, and extracted data. Primary outcomes were mortality and adverse events. We used the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach to rate quality of evidence and grade the strength of recommendation. RESULTS In seven trials enrolling 841 patients, assessment for risk of bias indicated variations in study quality from high (n = 4) to unclear (n = 3) resulting from a lack of adequate randomization, blinding, and incomplete outcomes. Polymyxin B-immobilized fiber therapy was associated with lower mortality (risk ratio, 0.65; 95% confidence interval [CI], 0.47-0.89; p = 0.007; I2 = 72%). Significant heterogeneity among trials was explained partly by study venue and baseline mortality rate. Meta-regression analysis revealed a significant negative slope between effect size of PMX-DHP therapy and baseline mortality rate in individual studies (p = 0.003), suggesting the probability of a beneficial effect with PMX-DHP increased with increasing baseline risk. Polymyxin B-immobilized fiber therapy did not increase the risk of hemoperfusion-related adverse events. The quality of the body of evidence was considered low for both mortality and adverse events. CONCLUSIONS Polymyxin B-immobilized fiber therapy was associated with reduced mortality in sepsis/septic shock. Based on the low quality of evidence, therapeutic use of PMX-DHP for survival benefit may be recommended conditionally for patients with high risk of death. Additional large randomized controlled trials are needed to confirm or refute this evidence.
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Affiliation(s)
- Takero Terayama
- 1 Department of Emergency and Critical Care, Osaka General Medical Center , Osaka, Japan
| | - Kazuma Yamakawa
- 2 Division of Trauma and Surgical Critical Care, Osaka General Medical Center , Osaka, Japan
| | - Yutaka Umemura
- 3 Department of Traumatology and Acute Critical Medicine, Osaka University Graduate School of Medicine , Osaka, Japan
| | - Morio Aihara
- 4 Department of Gastroenterology and Hematology, Hirosaki University Graduate School of Medicine , Hirosaki, Japan
| | - Satoshi Fujimi
- 1 Department of Emergency and Critical Care, Osaka General Medical Center , Osaka, Japan
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Cutuli SL, Artigas A, Fumagalli R, Monti G, Ranieri VM, Ronco C, Antonelli M. Polymyxin-B hemoperfusion in septic patients: analysis of a multicenter registry. Ann Intensive Care 2016; 6:77. [PMID: 27502196 PMCID: PMC4977232 DOI: 10.1186/s13613-016-0178-9] [Citation(s) in RCA: 34] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/23/2016] [Accepted: 07/18/2016] [Indexed: 12/17/2022] Open
Abstract
Background In 2010, the EUPHAS 2 collaborative group created a registry with the purpose of recording data from critically ill patients suffering from severe sepsis and septic shock treated with polymyxin-B hemoperfusion (PMX-HP) for endotoxin removal. The aim of the registry was to verify the application of PMX-HP in the daily clinical practice. Methods The EUPHAS 2 registry involved 57 centers between January 2010 and December 2014, collecting retrospective data of 357 patients (297 in Europe and 60 in Asia) suffering from severe sepsis and septic shock caused by proved or suspected infection related to Gram negative bacteria. All patients received atleast one cycle of extracorporeal endotoxin removal by PMX-HP. Results Septic shock was diagnosed in 305 (85.4 %) patients. The most common source of infection was abdominal (44.0 %) followed by pulmonary (17.6 %). Gram negative bacteria represented 60.6 % of the pathogens responsible of infection. After 72 h from the first cycle of PMX-HP, some of the SOFA score components significantly improved with respect to baseline: cardiovascular (2.16 ± 1.77 from 3.32 ± 1.29, p < 0.0001), respiratory (1.95 ± 0.95 from 2.40 ± 1.06, p < 0.001) and renal (1.84 ± 1.77 from 2.23 ± 1.62, p = 0.013). Overall 28-day survival rate was 54.5 % (60.4 % in abdominal and 47.5 % in pulmonary infection). Patients with abdominal infection treated with PMX-HP within 24 h from the diagnosis of septic shock had a 28-day survival rate of 64.5 %. Patients showing a significantly cardiovascular improvement after PMX-HP had a 28-survival rate of 75 % in comparison to the 39 % of patients who did not (p < 0.001). Cox regression analysis found the variation of cardiovascular, respiratory and coagulation SOFA to be independent covariates for 28-day survival. In European patients were observed a higher 28-day (58.8 vs. 34.5 %, p = 0.003), ICU (59 vs. 36.7 %, p = 0.006) and hospital survival rate (53.2 vs. 35 %, p = 0.02) than in Asian patients. However, the two populations were highly heterogeneous in terms of source of infection and severity scores at admission. Conclusion The EUPHAS 2 is the largest registry conducted outside Japan on the clinical use of PMX-HP in septic patients. Data analysis confirmed the feasibility of PMX-HP to treat septic patients in daily clinical practice, showing clinical benefits associated with endotoxin removal without significant adverse events related to the extracorporeal technique. Electronic supplementary material The online version of this article (doi:10.1186/s13613-016-0178-9) contains supplementary material, which is available to authorized users.
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Affiliation(s)
- Salvatore Lucio Cutuli
- Department of Intensive Care and Anaesthesiology, Agostino Gemelli University Hospital, Catholic University of the Sacred Heart, Largo A. Gemelli, 8, 00168, Rome, Italy.
| | - Antonio Artigas
- Critical Care Center, Sabadell Hospital, CIBER Enfermedades Respiratorias, Corporació Sanitària Universitària Parc Taulí, Universitat Autònoma de Barcelona, Sabadell, Spain
| | - Roberto Fumagalli
- Department of Anaesthesia and Intensive Care Medicine, Niguarda Ca' Granda Hospital, University of Milan-Bicocca, Milan, Italy
| | - Gianpaola Monti
- Department of Anaesthesia and Intensive Care Medicine, Niguarda Ca' Granda Hospital, University of Milan-Bicocca, Milan, Italy
| | - Vito Marco Ranieri
- Department of Anaesthesia and Intensive Care Medicine, University of Rome "La Sapienza", Rome, Italy
| | - Claudio Ronco
- Department of Nephrology, Dialysis and Transplantation, International Renal Research Institute of Vicenza (IRRIV), San Bortolo Hospital, Vicenza, Italy
| | - Massimo Antonelli
- Department of Intensive Care and Anaesthesiology, Agostino Gemelli University Hospital, Catholic University of the Sacred Heart, Largo A. Gemelli, 8, 00168, Rome, Italy
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Payen DM, Guilhot J, Launey Y, Lukaszewicz AC, Kaaki M, Veber B, Pottecher J, Joannes-Boyau O, Martin-Lefevre L, Jabaudon M, Mimoz O, Coudroy R, Ferrandière M, Kipnis E, Vela C, Chevallier S, Mallat J, Robert R. Early use of polymyxin B hemoperfusion in patients with septic shock due to peritonitis: a multicenter randomized control trial. Intensive Care Med 2015; 41:975-984. [PMID: 25862039 PMCID: PMC4477725 DOI: 10.1007/s00134-015-3751-z] [Citation(s) in RCA: 238] [Impact Index Per Article: 23.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/30/2014] [Accepted: 03/11/2015] [Indexed: 02/07/2023]
Abstract
PURPOSE To test whether the polymyxin B hemoperfusion (PMX HP) fiber column reduces mortality and organ failure in peritonitis-induced septic shock (SS) from abdominal infections. METHOD Prospective, multicenter, randomized controlled trial in 18 French intensive care units from October 2010 to March 2013, enrolling 243 patients with SS within 12 h after emergency surgery for peritonitis related to organ perforation. The PMX HP group received conventional therapy plus two sessions of PMX HP. Primary outcome was mortality on day 28; secondary outcomes were mortality on day 90 and a reduction in the severity of organ failures based on Sequential Organ Failure Assessment (SOFA) scores. PRIMARY OUTCOME day 28 mortality in the PMX HP group (n = 119) was 27.7 versus 19.5% in the conventional group (n = 113), p = 0.14 (OR 1.5872, 95% CI 0.8583-2.935). Secondary endpoints: mortality rate at day 90 was 33.6% in PMX-HP versus 24% in conventional groups, p = 0.10 (OR 1.6128, 95% CI 0.9067-2.8685); reduction in SOFA score from day 0 to day 7 was -5 (-11 to 6) in PMX-HP versus -5 (-11 to 9), p = 0.78. Comparable results were observed in the predefined subgroups (presence of comorbidity; adequacy of surgery, <2 sessions of hemoperfusion) and for SOFA reduction from day 0 to day 3. CONCLUSION This multicenter randomized controlled study demonstrated a non-significant increase in mortality and no improvement in organ failure with PMX HP treatment compared to conventional treatment of peritonitis-induced SS.
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Affiliation(s)
- Didier M. Payen
- />Department of Anesthesia and Critical Care, SAMU, Lariboisière University Hospital, University Paris 7 Denis Diderot, Paris, France
- />Paris Sorbone Cité and U 1160 INSERM, Paris, France
| | - Joelle Guilhot
- />Inserm Unit CIC 1402, La milèterie University Hospital, University Poitiers, Poitiers, France
| | - Yoann Launey
- />Department of Anesthesia and Critical Care, Pontchaillou University Hospital, University Rennes, Rennes, France
| | - Anne Claire Lukaszewicz
- />Department of Anesthesia and Critical Care, SAMU, Lariboisière University Hospital, University Paris 7 Denis Diderot, Paris, France
- />Paris Sorbone Cité and U 1160 INSERM, Paris, France
| | - Mahmoud Kaaki
- />Department of Intensive Care, Hospital of Roanne, Roanne, France
| | - Benoit Veber
- />Department of Anesthesia and Critical Care, University Charles Nicolle Hospital, University Rouen, Rouen, France
| | - Julien Pottecher
- />Department of Anesthesia and Critical Care, University Hospital Civil of Strasbourg, University Strasbourg, Strasbourg, France
| | - Olivier Joannes-Boyau
- />Department of Anesthesia and Critical Care, Haut-Lévêque University Hospital, University Bordeaux, Bordeaux, France
| | | | - Matthieu Jabaudon
- />Department of Anesthesia and Critical Care, D′Estaing University Hospital, University Clermont-Ferrand, Clermont-Ferrand, France
| | - Olivier Mimoz
- />Department of Anesthesia and Surgical Intensive Care, La Milèterie University Hospital, Poitiers University, Poitiers, France
| | - Rémi Coudroy
- />Department of Medical Intensive Care, La Milèterie University Hospital, Poitiers University, Poitiers, France
| | - Martine Ferrandière
- />Department of Anesthesia and Critical Care, Trousseau University Hospital, University Tours, Tours, France
| | - Eric Kipnis
- />Department of Anesthesia and Critical Care, Huriez University Hospital, University Lille, Lille, France
| | - Carlos Vela
- />Department of Anesthesia and Critical Care, University Hospital, Lille, France
| | | | - Jihad Mallat
- />Medical-Surgical Intensive Care, District Hospital, Saint-Malo, France
| | - René Robert
- />Medical Intensive Care, La milèterie University Hospital, University Poitiers, Poitiers, France
| | - The ABDOMIX Group
- />Department of Anesthesia and Critical Care, SAMU, Lariboisière University Hospital, University Paris 7 Denis Diderot, Paris, France
- />Paris Sorbone Cité and U 1160 INSERM, Paris, France
- />Inserm Unit CIC 1402, La milèterie University Hospital, University Poitiers, Poitiers, France
- />Department of Anesthesia and Critical Care, Pontchaillou University Hospital, University Rennes, Rennes, France
- />Department of Intensive Care, Hospital of Roanne, Roanne, France
- />Department of Anesthesia and Critical Care, University Charles Nicolle Hospital, University Rouen, Rouen, France
- />Department of Anesthesia and Critical Care, University Hospital Civil of Strasbourg, University Strasbourg, Strasbourg, France
- />Department of Anesthesia and Critical Care, Haut-Lévêque University Hospital, University Bordeaux, Bordeaux, France
- />Medical-Surgical Intensive Care, District Hospital, La Roche Sur-Yon, France
- />Department of Anesthesia and Critical Care, D′Estaing University Hospital, University Clermont-Ferrand, Clermont-Ferrand, France
- />Department of Anesthesia and Surgical Intensive Care, La Milèterie University Hospital, Poitiers University, Poitiers, France
- />Department of Medical Intensive Care, La Milèterie University Hospital, Poitiers University, Poitiers, France
- />Department of Anesthesia and Critical Care, Trousseau University Hospital, University Tours, Tours, France
- />Department of Anesthesia and Critical Care, Huriez University Hospital, University Lille, Lille, France
- />Department of Anesthesia and Critical Care, University Hospital, Lille, France
- />Department of Intensive Care, Saint-Jean Hospital, Perpignan, France
- />Medical-Surgical Intensive Care, District Hospital, Saint-Malo, France
- />Medical Intensive Care, La milèterie University Hospital, University Poitiers, Poitiers, France
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Chang HW, Cho YJ, Park SH, Kim M. Polymyxin B Immobilized Fiber Hemoperfusion in Refractory Intra-abdominal Septic Shock. Korean J Crit Care Med 2015. [DOI: 10.4266/kjccm.2015.30.2.95] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/30/2022] Open
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Darmon M, Bagshaw SM, Forni LG. Balancing the "humors" in severe sepsis: still a role for extracorporeal therapies? Intensive Care Med 2015; 41:1132-4. [PMID: 25971380 DOI: 10.1007/s00134-015-3801-6] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/02/2015] [Accepted: 04/03/2015] [Indexed: 01/20/2023]
Affiliation(s)
- Michael Darmon
- Medical-Surgical Intensive Care Unit, Saint-Etienne University Hospital, Avenue Albert Raymond, 42270, Saint-Priest-En-Jarez, France,
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Wang YQ, Wang B, Liang Y, Cao SH, Liu L, Xu XN. Role of platelet TLR4 expression in pathogensis of septic thrombocytopenia. World J Emerg Med 2014; 2:13-7. [PMID: 25214976 DOI: 10.5847/wjem.j.1920-8642.2011.01.002] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/27/2010] [Accepted: 12/15/2010] [Indexed: 02/01/2023] Open
Abstract
BACKGROUND Infection-induced thrombocytopenia (TCP) is an independent risk factor for death of patients with sepsis, but its mechanism is unknown. This study aimed to explore the underlying mechanism of TCP based on the relationship between TLR4 expression and platelet activation in septic patients. METHODS A total of 64 patients with sepsis were prospectively studied. Platelet count (PC), mean platelet volume (MPV), platelet distribution width (PDW), platelet TLR4 expression, platelet PAC-1 expression, sCD40L and TNF-α concentrations were compared between the healthy control group (15 volunteers) and sepsis group (64 patients) at admission and on the 3, 5, and 9 days after admission. The changes of MPV and PDW in the TCP and non-TCP subgroups of sepsis before and after treatment were recorded. Prognostic index was analyzed. RESULTS PC was lower in the sepsis group (P=0.006), and MPV and PDW were higher in the sepsis group than those in the healthy control group (P=0.046, P=0.001). Platelet TLR4 and PAC-1 expressions, and sCD40L and TNF-α levels increased more significantly in the sepsis group (P<0.001). PAC-1 expression and TNF-α level were higher in the TCP group than in the non-TCP group before and after treatment (P=0.023, P=0.011). sCD40L concentration and platelet TLR4 expression were significantly higher in the treated TCP group than in the non-TCP group (P=0.047, P=0.001). Compared to the non-TCP group, the rate of bleeding was higher (P=0.024) and the length of ICU stay was longer (P=0.013). The APACHE II score and the 28-day mortality were higher in the TCP group (P<0.01, P=0.048). CONCLUSIONS The elevation of platelet TLR4 expression in sepsis along with platelet activation is closely related to the incidence of thrombocytopenia. The occurrence of TCP is a sign of poor prognosis in sepsis patients.
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Affiliation(s)
- Yong-Qiang Wang
- ICU, Tianjin First Center Hospitial, Tianjin 300192, China (WangYQ, Wang B, Cao SH, Xu XN); Tianjin University of Traditional Chinese Medicine, Tianjin 300193, China (Liang Y); General Hospital of Tianjin Medical University, Tianjin 300052, China (Liu L)
| | - Bing Wang
- ICU, Tianjin First Center Hospitial, Tianjin 300192, China (WangYQ, Wang B, Cao SH, Xu XN); Tianjin University of Traditional Chinese Medicine, Tianjin 300193, China (Liang Y); General Hospital of Tianjin Medical University, Tianjin 300052, China (Liu L)
| | - Yong Liang
- ICU, Tianjin First Center Hospitial, Tianjin 300192, China (WangYQ, Wang B, Cao SH, Xu XN); Tianjin University of Traditional Chinese Medicine, Tianjin 300193, China (Liang Y); General Hospital of Tianjin Medical University, Tianjin 300052, China (Liu L)
| | - Shu-Hua Cao
- ICU, Tianjin First Center Hospitial, Tianjin 300192, China (WangYQ, Wang B, Cao SH, Xu XN); Tianjin University of Traditional Chinese Medicine, Tianjin 300193, China (Liang Y); General Hospital of Tianjin Medical University, Tianjin 300052, China (Liu L)
| | - Li Liu
- ICU, Tianjin First Center Hospitial, Tianjin 300192, China (WangYQ, Wang B, Cao SH, Xu XN); Tianjin University of Traditional Chinese Medicine, Tianjin 300193, China (Liang Y); General Hospital of Tianjin Medical University, Tianjin 300052, China (Liu L)
| | - Xin-Nv Xu
- ICU, Tianjin First Center Hospitial, Tianjin 300192, China (WangYQ, Wang B, Cao SH, Xu XN); Tianjin University of Traditional Chinese Medicine, Tianjin 300193, China (Liang Y); General Hospital of Tianjin Medical University, Tianjin 300052, China (Liu L)
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Rilinger JF, Hussain E, McBride ME. Adjunctive Therapies in Sepsis. CLINICAL PEDIATRIC EMERGENCY MEDICINE 2014. [DOI: 10.1016/j.cpem.2014.04.001] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
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Abstract
Endotoxin, one of the principal components on the outer membrane of Gram-negative bacteria, is considered a key and early component in the pathogenesis of sepsis. Polymyxin B bound to polystyrene fibers (PMX) is a medical device capable of removing circulating endotoxin by adsorption. The most comprehensive analysis to date of clinical experience with this device remains a meta-analysis of 28 studies between 1998 and 2006. This showed that PMX hemoperfusion was associated with improved blood pressure and a reduction in dopamine dose, improved PaO2/FiO2 ratio and lower mortality. Since this meta-analysis, over 50 additional studies on PMX have been published. The majority are observational, with small sample sizes. Notable among the newer studies is the increasing interest in the use of PMX therapy in interstitial pneumonias and idiopathic pulmonary fibrosis, as well as in longer treatment duration and earlier initiation of PMX therapy in an attempt to further improve clinical outcomes. These observational data highlight important aspects of PMX therapy worthy of more rigorous investigation in future studies.
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Affiliation(s)
- Dinna N Cruz
- Division of Nephrology-Hypertension, University of California, San Diego, Calif., USA
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Abstract
One of the key molecules involved in the pathogenesis of severe sepsis and septic shock is lipopolysaccharide (LPS) or endotoxin, which is a component of the cellular wall of Gram-negative bacteria. Clinical studies have shown that the level of circulating LPS is correlated with illness severity (APACHE II), the onset and amount of organ dysfunction (SOFA) and intensive care unit mortality. Many therapeutic strategies have attempted to neutralize the pathogenic activity of endotoxin in order to interrupt the progression of a septic state towards a worsened clinical framework, i.e. severe sepsis of septic shock. Over the past decades the role of extracorporeal hemoperfusion by means of polymyxin B-based cartridges (PMX-DHP) to bind and neutralize LPS from whole blood has increased in clinical relevance. This is due to an increasing number of studies confirming that a directed therapy of endotoxic shock could significantly influence the course of the septic cascade. This review will outline the meaning of the targeted approach to endotoxin, both highlighting the specific immunologic effect of endotoxin removal by polymyxin B and the evidence of clinical improvements following this kind of therapy in terms of recovery of organ function.
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Affiliation(s)
- Claudio Ronco
- Department of Nephrology, Ospedale San Bortolo, Vicenza, Italy
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28
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Blood purification and mortality in sepsis: a meta-analysis of randomized trials. Crit Care Med 2013; 41:2209-20. [PMID: 23860248 DOI: 10.1097/ccm.0b013e31828cf412] [Citation(s) in RCA: 116] [Impact Index Per Article: 9.7] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Abstract
OBJECTIVES Although blood purification improves outcomes in animal studies of sepsis, results of clinical trials have been mixed. We conducted a systematic review and meta-analysis of randomized trials to determine the association between various blood purification techniques and all-cause mortality in humans with sepsis. DATA SOURCES We searched for relevant studies in MEDLINE, EMBASE, and the Cochrane Library database from January 1966 to May 2012. STUDY SELECTION Inclusion required a diagnosis of sepsis and comparison of blood purification techniques including hemofiltration, hemoperfusion, plasma exchange, or hemodialysis with no blood purification (control group). DATA EXTRACTION Two authors independently selected studies and extracted data. Summary statistics, risk ratios, and CIs were calculated using random-effects modeling. Study quality was assessed using Jadad score, and publication bias was assessed using funnel plots and Egger's statistic. DATA SYNTHESIS Overall, blood purification decreased mortality compared with no blood purification (35.7% vs 50.1%; risk ratio, 0.69 [95% CI, 0.56-0.84]; p<0.001; 16 trials, n=827). However, these results were driven mainly by hemoperfusion (risk ratio, 0.63 [95% CI, 0.50-0.80]; p<0.001; 10 trials, n=557) and plasma exchange (risk ratio, 0.63 [95% CI, 0.42-0.96]; p=0.03; two trials, n=128). Pooling of all trials of blood purification for treatment of sepsis was no longer associated with lower mortality (risk ratio, 0.89 [95% CI, 0.71-1.13]; p=0.36; eight trials, n=457) after excluding trials using polymyxin B hemoperfusion. CONCLUSIONS Blood purification techniques including hemoperfusion, plasma exchange, and hemofiltration with hemoperfusion were associated with lower mortality in patients with sepsis. These results were mainly influenced by studies using polymyxin B hemoperfusion from Japan.
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Immunomodulation in sepsis: the role of endotoxin removal by polymyxin B-immobilized cartridge. Mediators Inflamm 2013; 2013:507539. [PMID: 24249974 PMCID: PMC3819752 DOI: 10.1155/2013/507539] [Citation(s) in RCA: 45] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/29/2013] [Accepted: 09/16/2013] [Indexed: 12/14/2022] Open
Abstract
Severe sepsis results in high morbidity and mortality. Immunomodulation strategies could be an adjunctive therapy to treat sepsis. Endotoxin is a component of gram-negative bacteria and plays an important role in the pathogenesis of septic shock when it is recognized by immune cells. Removal of endotoxin could be an effective adjunctive approach to the management of sepsis. Devices to adsorb endotoxin or inflammatory cytokines have been designed as a strategy to treat severe sepsis, especially sepsis caused by gram-negative bacteria. Polymyxin B-immobilized cartridge has been successfully used to treat patients with sepsis of abdominal origin. Although this cartridge was conceived to adsorb endotoxin, several other immunological mechanisms have been elucidated, and this device has also yielded promising results in patients with nonseptic respiratory failure. In this paper, we summarize the immune modulation actions of Polymyxin B-immobilized cartridge to explore its potential usefulness beyond endotoxin elimination.
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30
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Prechel MM, Walenga JM. Emphasis on the Role of PF4 in the Incidence, Pathophysiology and Treatment of Heparin Induced Thrombocytopenia. Thromb J 2013; 11:7. [PMID: 23561460 PMCID: PMC3627638 DOI: 10.1186/1477-9560-11-7] [Citation(s) in RCA: 33] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/13/2012] [Accepted: 03/25/2013] [Indexed: 01/11/2023] Open
Abstract
Heparin Induced Thrombocytopenia (HIT) is caused by antibodies that recognize platelet factor 4 (PF4) associated with polyanionic glycosaminoglycan drugs or displayed on vascular cell membranes. These antibodies are elicited by multimolecular complexes that can occur when heparin is administered in clinical settings associated with abundant PF4. Heparin binding alters native PF4 and elicits immune recognition and response. While the presence of heparin is integral to immunogenesis, the HIT antibody binding site is within PF4. Thus HIT antibodies develop and function to cause thrombocytopenia and/or thrombosis only in the presence of PF4. Future emphasis on understanding the biology, turnover and regulation of PF4 may lead to insights into the prevention and treatment of HIT.
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Affiliation(s)
- M Margaret Prechel
- Departments of Pathology and Thoracic & Cardiovascular Surgery, Loyola University Medical Center, Bldg 110, Rm 5225, 2160 S, First Avenue, Maywood, IL 60153, USA.
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David SA. Antimicrobial peptides for gram-negative sepsis: a case for the polymyxins. Front Immunol 2012; 3:252. [PMID: 22912638 PMCID: PMC3419356 DOI: 10.3389/fimmu.2012.00252] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/28/2012] [Accepted: 07/30/2012] [Indexed: 01/10/2023] Open
Affiliation(s)
- Sunil A David
- Department of Medicinal Chemistry, University of Kansas Lawrence, KS, USA
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Abstract
Endotoxin, an outer membrane component of gram-negative bacteria, plays an important role in the pathogenesis of septic shock. Endotoxin adsorption therapy by polymyxin B-immobilized fiber column hemoperfusion (PMX) has been used for the treatment of septic shock patients in Japan since 1994. The covalent binding of polymyxin B onto the surface of the polystyrene-based carrier fiber in PMX inactivates the endotoxin in the blood without exerting toxicity. This study was performed as a systematic review to evaluate the efficacy and mechanism of PMX treatment in patients with septic shock. The PubMed database and references from identified articles were used to search and review the literature relating to the efficacy and mechanism of PMX treatment in patients with septic shock. Polymyxin B-immobilized fiber column hemoperfusion adsorbed monocytes, activated neutrophils, and anandamide, as well as endotoxin through direct covalent bond, hydrophobic and ionic interactions, and hydrodynamics, and reduced the blood concentrations of inflammatory cytokines, plasminogen activator inhibitor 1 and adhesion molecules. Polymyxin B-immobilized fiber column hemoperfusion increased blood pressure and reduced the dosage requirements for vasopressive/inotropic agents. The meta-analysis showed that PMX treatment had beneficial effects on the hemodynamics, pulmonary oxygenation, and mortality. These beneficial effects may be attributable to the direct adsorption of endotoxin, monocytes, activated neutrophils, and anandamide, as well as indirect decrease in inflammatory cytokines and other mediators. Polymyxin B-immobilized fiber column hemoperfusion treatment has additional effects on reducing endothelial damage, proapoptotic activity, and immunosuppression. Further studies will be needed to confirm the efficacy and mechanism of PMX treatment in septic shock.
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Abstract
The treatment of sepsis is an ongoing challenge for clinicians; despite the wide choice of effective antibiotics to treat infection, sepsis remains the leading cause of morbidity and mortality for patients admitted to an intensive care unit. Dysregulation of the immune response is now recognized to be a key factor in multiple organ dysfunction, yet our therapy for inflammation remains ineffective. It has been advocated for more than a decade that cytokine reduction in blood compartment could lead to a reduction in mortality in sepsis. Over the years, multiple extracorporeal techniques have evolved, with the intent of influencing the circulating levels of inflammatory mediators like cytokines and chemokines, the complement system, as well as factors of the coagulation system. These include high-volume hemofiltration, use of high cutoff membranes, and systems based on adsorption, such as coupled plasma filtration adsorption and the polymyxin-B column. In addition, new experimental systems that utilize human phagocytic cells and immobilized antibodies for targeted immunomodulation have emerged. In the context of limited resources and growing expansion in the availability of technologies, a better understanding of these therapies is required before they can be properly integrated into standard clinical practice in the hope of influencing major clinical outcomes. In this article, we will provide a concise overview of selected extracorporeal modalities currently in clinical use and briefly introduce some new promising techniques for sepsis.
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Affiliation(s)
- Anthi Panagiotou
- Department of Nephrology Dialysis & Transplantation, San Bortolo Hospital, Vicenza, Italy
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Huttunen R, Aittoniemi J. New concepts in the pathogenesis, diagnosis and treatment of bacteremia and sepsis. J Infect 2011; 63:407-19. [PMID: 21840338 DOI: 10.1016/j.jinf.2011.08.004] [Citation(s) in RCA: 44] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/18/2011] [Revised: 08/01/2011] [Accepted: 08/04/2011] [Indexed: 01/05/2023]
Abstract
Bacteremia and sepsis are major health concerns. Despite intensive research, there are only a limited number of successful treatment options, and it is difficult to see the forest for the trees when considering the pathogenesis of this condition. Studies in the last decade have shown that a major pathophysiologic event in sepsis is the progression from proinflammation to an immunosuppressive state. However, recent genome-based data indicate that sepsis-related inflammatory responses are highly variable, which calls in question the classic two-phase model of sepsis. Adequate and timely antimicrobial treatment is a cornerstone for survival in patients with bacteremia and sepsis. However, microbial resistance has emerged as an increasing challenge for clinicians and with an increasing number of resistant pathogens causing infections, selection of empiric antimicrobial treatment has become difficult. Treatment options currently under way are targeted to enhance immune responses, rebalance the regulation of the dysregulated immune system, remove endotoxin and block/inhibit apoptosis.
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Affiliation(s)
- Reetta Huttunen
- Department of Internal Medicine, Tampere University Hospital, Box 2000, FI-33521 Tampere, Finland.
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35
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Sato K, Maekawa H, Sakurada M, Orita H, Komatsu Y. Direct hemoperfusion with polymyxin B immobilized fiber for abdominal sepsis in Europe. Surg Today 2011; 41:754-60. [PMID: 21626318 DOI: 10.1007/s00595-010-4504-9] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
Since direct hemoperfusion with polymyxin B immobilized fiber (PMX-DHP) received its product certification for use in Europe in 1998, several prospective randomized controlled trials (RCTs) have been conducted in European countries. The first RCT, performed in six European academic medical centers in 2005, concluded that PMX-DHP is associated with improved hemodynamic status and cardiac function. Subsequently, a meta-analysis of PMX-DHP was presented in Italy in 2007. This systematic review found positive effects of PMX-DHP on mean arterial pressure and dopamine/ dobutamine use, PaO2/FiO2 ratio, endotoxin removal, and mortality. However, like most trials on extracorporeal therapies, none of the studies was double-blinded. The EUPHAS study, a multicenter RCT performed in ten Italian intensive care units in 2009, found that PMX-DHP improved 28-day survival, blood pressure, vasopressor requirement, and degree of organ failure. However, investigators in Belgium and Canada pointed out that there was no statistical difference in 28-day survival. Two more RCTs, the ABDO-MIX and EUPHRATES studies, the primary end points of which are 28-day mortality, were started in Europe and the United States at the end of 2010. We are hoping that these RCTs will resolve this issue.
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Affiliation(s)
- Koichi Sato
- Department of Surgery, Juntendo Shizuoka Hospital, Juntendo University School of Medicine, 1129 Izunokuni, Shizuoka, 410-2295, Japan
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A longer duration of polymyxin B-immobilized fiber column hemoperfusion improves pulmonary oxygenation in patients with septic shock. Shock 2010; 32:478-83. [PMID: 19295483 DOI: 10.1097/shk.0b013e3181a2a978] [Citation(s) in RCA: 40] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/16/2023]
Abstract
Endotoxin plays an important role in the pathogenesis of septic shock. Exposure of endothelial cells to endotoxin activates endothelial cells and increases the surface expression of adhesion molecules, markers of endothelial damage in organ dysfunction. Endotoxin adsorption therapy by polymyxin B-immobilized fiber column (PMX) hemoperfusion has been used for the treatment of septic shock patients. In this study, we measured plasma concentrations of endotoxin and soluble adhesion molecules in septic shock patients before and after the PMX treatment then observed on the relationships between actual duration of use and various outcomes. Sixteen patients with septic shock were studied. The 28-day mortality rate was 50%. The elevated plasma concentrations of endotoxin decreased after the PMX treatment in the survivors but not in the nonsurvivors. The norepinephrine dose and plasma concentrations of soluble endothelial leukocyte adhesion molecule 1 and soluble intercellular adhesion molecule 1 significantly (P < 0.05) decreased in the PMX greater-than-2-h (prolonged) group than in the PMX 2-h (conventional) group (-17.8 +/- 14.6 vs. -1.8 +/- 2.7 microg/min, -143.0 +/- 111.0 vs. 0 +/- 2.8 ng/mL, and -126.2 +/- 144.9 vs. 16.5 +/- 108.1 ng/mL, respectively). Changes in the PaO2-FiO2 ratio and the Sequential Organ Failure Assessment score were significantly (P < 0.05) more improved in the PMX greater-than-2-h group than in the PMX 2-h group (75.4 +/- 80.7 vs. 1.2 +/- 49.2 and -0.8 +/- 1.8 vs. 2.2 +/- 1.9 torr, respectively). We thus suggest that a longer duration of PMX treatment may improve the pulmonary oxygenation associated with decreased adhesion molecules in septic shock.
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Pierrakos C, Vincent JL. Sepsis biomarkers: a review. CRITICAL CARE : THE OFFICIAL JOURNAL OF THE CRITICAL CARE FORUM 2010; 14:R15. [PMID: 20144219 PMCID: PMC2875530 DOI: 10.1186/cc8872] [Citation(s) in RCA: 865] [Impact Index Per Article: 57.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 07/10/2009] [Revised: 12/28/2009] [Accepted: 02/09/2010] [Indexed: 02/06/2023]
Abstract
INTRODUCTION Biomarkers can be useful for identifying or ruling out sepsis, identifying patients who may benefit from specific therapies or assessing the response to therapy. METHODS We used an electronic search of the PubMed database using the key words "sepsis" and "biomarker" to identify clinical and experimental studies which evaluated a biomarker in sepsis. RESULTS The search retrieved 3370 references covering 178 different biomarkers. CONCLUSIONS Many biomarkers have been evaluated for use in sepsis. Most of the biomarkers had been tested clinically, primarily as prognostic markers in sepsis; relatively few have been used for diagnosis. None has sufficient specificity or sensitivity to be routinely employed in clinical practice. PCT and CRP have been most widely used, but even these have limited ability to distinguish sepsis from other inflammatory conditions or to predict outcome.
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Affiliation(s)
- Charalampos Pierrakos
- Department of Intensive Care, Erasme Hospital, Université Libre de Bruxelles, route de Lennik 808, 1070 Brussels, Belgium.
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Abstract
Sepsis, otherwise referred to as "blood poisoning" is a serious clinical problem, the incidence of which continues to rise in the US and worldwide despite advances in antimicrobial chemotherapy. The primary trigger in Gram-negative sepsis is endotoxin, a lipopolysaccharide (LPS) constituent of the outer membrane of all Gram-negative bacteria. The structurally highly conserved glycolipid called lipid A is the active moiety of LPS. Lipid A is composed of a hydrophilic, bis-phosphorylated di-glucosamine backbone, and a hydrophobic polyacyl domain. The bis-anionic, amphiphilic nature of lipid A enables it to interact with a variety of cationic hydrophobic ligands, including polymyxin B, a toxic peptide antibiotic which binds to lipid A and neutralizes endotoxicity. Having determined the structural basis of the interaction of polymyxin B with lipid A, our long-term goal has been to rationally design non-peptidic, nontoxic, small-molecule LPS-sequestrants. Our efforts began with defining the central pharmacophore that determined LPS-recognition and -neutralization properties in small molecules, which led to the discovery of a novel lipopolyamine lead, DS-96. DS-96 is an effective LPS-neutralizer, rivaling polymyxin B in a panel of vitro assays, as well as in protecting animals against endotoxicosis. Structure-activity relationships in our effort to rationally design endotoxin sequestering agents, preclinical assessment of hits and leads, and approaches to overcoming issues with toxicity are described in this chapter.
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Affiliation(s)
- Sunil A David
- Department of Medicinal Chemistry, University of Kansas, Multidisciplinary Research Building, Room 320D, 2030 Becker Drive, Lawrence, KS 66047, USA.
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Hou G, Liu T, Wang H, Fu G, Yuan Z, Liu B, Sun L, Fang J, Li D, Qiu Q. Preparation of Adsorbents for the Removal of Endotoxin. ACTA ACUST UNITED AC 2009; 33:227-37. [PMID: 15960082 DOI: 10.1081/bio-200055924] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/03/2022]
Abstract
By using the agar beads as the support, L-lysine as the ligand, three kinds of absorbents with different spacers for removal of endotoxin were prepared. The adsorption capacity of three adsorbents was compared. Among them, Ag3, with L-lysine ligand and hexamethylendiamine as the spacer, was the best in adsorption capacity and was selected for hemoperfusion on rabbits. The results showed the level of endotoxin in endotoxemia rabbit after hemoperfusion was near normal level. The clearance percentage of endotoxin was 73.6%
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Affiliation(s)
- Guanghui Hou
- The State Key Laboratory of Functional Polymer Materials for Adsorption and Separation, Institute of Polymer Chemistry, Nankai University, Tianjin, China
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Kingsmore SF, Kennedy N, Halliday HL, Van Velkinburgh JC, Zhong S, Gabriel V, Grant J, Beavis WD, Tchernev VT, Perlee L, Lejnine S, Grimwade B, Sorette M, Edgar JDM. Identification of diagnostic biomarkers for infection in premature neonates. Mol Cell Proteomics 2008; 7:1863-75. [PMID: 18622029 DOI: 10.1074/mcp.m800175-mcp200] [Citation(s) in RCA: 42] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/15/2023] Open
Abstract
Infection is a leading cause of neonatal morbidity and mortality worldwide. Premature neonates are particularly susceptible to infection because of physiologic immaturity, comorbidity, and extraneous medical interventions. Additionally premature infants are at higher risk of progression to sepsis or severe sepsis, adverse outcomes, and antimicrobial toxicity. Currently initial diagnosis is based upon clinical suspicion accompanied by nonspecific clinical signs and is confirmed upon positive microbiologic culture results several days after institution of empiric therapy. There exists a significant need for rapid, objective, in vitro tests for diagnosis of infection in neonates who are experiencing clinical instability. We used immunoassays multiplexed on microarrays to identify differentially expressed serum proteins in clinically infected and non-infected neonates. Immunoassay arrays were effective for measurement of more than 100 cytokines in small volumes of serum available from neonates. Our analyses revealed significant alterations in levels of eight serum proteins in infected neonates that are associated with inflammation, coagulation, and fibrinolysis. Specifically P- and E-selectins, interleukin 2 soluble receptor alpha, interleukin 18, neutrophil elastase, urokinase plasminogen activator and its cognate receptor, and C-reactive protein were observed at statistically significant increased levels. Multivariate classifiers based on combinations of serum analytes exhibited better diagnostic specificity and sensitivity than single analytes. Multiplexed immunoassays of serum cytokines may have clinical utility as an adjunct for rapid diagnosis of infection and differentiation of etiologic agent in neonates with clinical decompensation.
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Cruz DN, Perazella MA, Bellomo R, de Cal M, Polanco N, Corradi V, Lentini P, Nalesso F, Ueno T, Ranieri VM, Ronco C. Effectiveness of polymyxin B-immobilized fiber column in sepsis: a systematic review. CRITICAL CARE : THE OFFICIAL JOURNAL OF THE CRITICAL CARE FORUM 2008; 11:R47. [PMID: 17448226 PMCID: PMC2206475 DOI: 10.1186/cc5780] [Citation(s) in RCA: 217] [Impact Index Per Article: 12.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 01/04/2007] [Revised: 03/01/2007] [Accepted: 04/20/2007] [Indexed: 12/18/2022]
Abstract
INTRODUCTION Severe sepsis and septic shock are common problems in the intensive care unit and carry a high mortality. Endotoxin, one of the principal components on the outer membrane of gram-negative bacteria, is considered important to their pathogenesis. Polymyxin B bound and immobilized to polystyrene fibers (PMX-F) is a medical device that aims to remove circulating endotoxin by adsorption, theoretically preventing the progression of the biological cascade of sepsis. We performed a systematic review to describe the effect in septic patients of direct hemoperfusion with PMX-F on outcomes of blood pressure, use of vasoactive drugs, oxygenation, and mortality reported in published studies. METHODS We searched PubMed, the Cochrane Collaboration Database, and bibliographies of retrieved articles and consulted with experts to identify relevant studies. Prospective and retrospective observational studies, pre- and post-intervention design, and randomized controlled trials were included. Three authors reviewed all citations. We identified a total of 28 publications - 9 randomized controlled trials, 7 non-randomized parallel studies, and 12 pre-post design studies - that reported at least one of the specified outcome measures (pooled sample size, 1,425 patients: 978 PMX-F and 447 conventional medical therapy). RESULTS Overall, mean arterial pressure (MAP) increased by 19 mm Hg (95% confidence interval [CI], 15 to 22 mm Hg; p < 0.001), representing a 26% mean increase in MAP (range, 14% to 42%), whereas dopamine/dobutamine dose decreased by 1.8 microg/kg per minute (95% CI, 0.4 to 3.3 microg/kg per minute; p = 0.01) after PMX-F. There was significant intertrial heterogeneity for these outcomes (p < 0.001), which became non-significant when analysis was stratified for baseline MAP. The mean arterial partial pressure of oxygen/fraction of inspired oxygen (PaO2/FiO2) ratio increased by 32 units (95% CI, 23 to 41 units; p < 0.001). PMX-F therapy was associated with significantly lower mortality risk (risk ratio, 0.53; 95% CI, 0.43 to 0.65). The trials assessed had suboptimal method quality. CONCLUSION Based on this critical review of the published literature, direct hemoperfusion with PMX-F appears to have favorable effects on MAP, dopamine use, PaO2/FiO2 ratio, and mortality. However, publication bias and lack of blinding need to be considered. These findings support the need for further rigorous study of this therapy.
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Affiliation(s)
- Dinna N Cruz
- Department of Nephrology, Ospedale San Bortolo, Viale Rodolfi 37, 36100 Vicenza, Italy
- Section of Nephrology, Department of Medicine, St. Luke's Medical Center, 279 E Rodriguez Sr Boulevard, Quezon City 1102, Philippines
| | - Mark A Perazella
- Section of Nephrology, Department of Medicine, Yale University School of Medicine, 333 Cedar Street FMP 107, New Haven, CT 06520, USA
| | - Rinaldo Bellomo
- Department of Intensive Care and Department of Medicine, Austin & Repatriation Medical Centre, Studley Road, Heidelberg, Victoria 3084, Australia
| | - Massimo de Cal
- Department of Nephrology, Ospedale San Bortolo, Viale Rodolfi 37, 36100 Vicenza, Italy
| | - Natalia Polanco
- Department of Nephrology, Ospedale San Bortolo, Viale Rodolfi 37, 36100 Vicenza, Italy
| | - Valentina Corradi
- Department of Nephrology, Ospedale San Bortolo, Viale Rodolfi 37, 36100 Vicenza, Italy
| | - Paolo Lentini
- Department of Nephrology, Ospedale San Bortolo, Viale Rodolfi 37, 36100 Vicenza, Italy
| | - Federico Nalesso
- Department of Nephrology, Ospedale San Bortolo, Viale Rodolfi 37, 36100 Vicenza, Italy
| | - Takuya Ueno
- Transplantation Unit, Surgical Services, Massachusetts General Hospital, 55 Fruit Street White 506, Boston, MA 02114, USA
| | - V Marco Ranieri
- Department of Anesthesia and Intensive Care, Ospedale San Giovanni Battista, Corso Bramante 88, 10126 Torino, Italy
| | - Claudio Ronco
- Department of Nephrology, Ospedale San Bortolo, Viale Rodolfi 37, 36100 Vicenza, Italy
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Sakamoto Y, Mashiko K, Matsumoto H, Hara Y, Kutsukata N, Yamamoto Y. Relationship between effect of polymyxin B-immobilized fiber and high-mobility group box-1 protein in septic shock patients. ASAIO J 2007; 53:324-8. [PMID: 17515723 DOI: 10.1097/mat.0b013e3180340301] [Citation(s) in RCA: 32] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/20/2023] Open
Abstract
Direct hemoperfusion (DHP) using a polymyxin B (PMX)-immobilized fiber column has been used for treatment of endotoxemia-induced septic shock in Japan since 1994 and is now an accepted therapy for reducing serum endotoxin levels. Although a reduction in inflammatory cytokines has been reported, the detailed mechanism of DHP-PMX is not known. We investigated the high-mobility group box-1 (HMGB-1) level in septic shock patients treated with DHP-PMX. Subjects (n = 20) were separated into two group: those whose systolic blood pressure increased to more than 30 mm Hg immediately after DHP-PMX (effective [E] group: nine cases) and those whose systolic blood pressure did not increase to more than 30 mm Hg (noneffective [N-E] group: 11 cases). The interleukin-6, plasminogen activator inhibitor-1, and HMGB-1 levels were measured in each group. The Pao2/Fio2 ratio and the Sepsis-Related Organ Failure Assessment (SOFA) score were also evaluated. Pretreatment interleukin-6, plasminogen activator inhibitor-1, and HMGB-1 levels were similar in the E and N-E groups, but mortality rate was significantly higher in the N-E group. Furthermore, posttreatment SOFA score was significantly lower in the E group. In the E group, only the HMGB-1 levels improved significantly after DHP-PMX. Present data suggest that the circulation dynamics of septic shock patients can be improved by reducing HMGB-1 levels by using DHP-PMX.
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Affiliation(s)
- Yuichiro Sakamoto
- Department of Emergency and Critical Care Medicine, Chiba-Hokusoh Hospital, Nippon Medical School, Chiba, Japan
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Sakamoto Y, Mashiko K, Matsumoto H, Hara Y, Kutsukata N, Takei K, Ueno Y, Tomita Y, Yamamoto Y. Effect of direct hemoperfusion with a polymyxin B immobilized fiber column on high mobility group box-1 (HMGB-1) in severe septic shock: report of a case. ASAIO J 2007; 52:e37-9. [PMID: 17117045 DOI: 10.1097/01.mat.0000248996.22865.ce] [Citation(s) in RCA: 14] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022] Open
Abstract
Because of the many difficult aspects in the treatment of septic shock and poor outcome of this condition, establishing the most appropriate therapeutic strategy is problematic. Recently, high mobility group box-1 (HMGB-1) has been shown to activate inflammatory responses and to be a late mediator in endotoxemia and sepsis. Therefore, we considered that it might be worthwhile to investigate the therapeutic potential of HMGB-1 blockade in cases of septic shock.Herein, we describe the case of a patient with septic shock with hepatic portal venous gas caused by intestinal obstruction. Hepatic portal venous gas is a rare condition associated with significant radiographic findings and a fatal outcome. Our patient, however, recovered from severe septic shock and was saved by the use of direct hemoperfusion with a polymyxin B immobilized fiber column (DHP-PMX). This treatment resulted in a decrease in the serum levels of endotoxin, interleukin-6 (IL-6), and HMGB-1.
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Affiliation(s)
- Yuichiro Sakamoto
- Department of Emergency and Critical Care Medicine, Chiba Hokisou Hospital, Nippon Medical School, Inba-Gun, Chiba, Japan
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Morresey PR, Mackay RJ. Endotoxin-neutralizing activity of polymyxin B in blood after IV administration in horses. Am J Vet Res 2006; 67:642-7. [PMID: 16579757 DOI: 10.2460/ajvr.67.4.642] [Citation(s) in RCA: 41] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022]
Abstract
OBJECTIVES To measure serum polymyxin B concentration after single and repeated IV infusions in horses. ANIMALS 5 healthy horses. PROCEDURES In study 1, 1 mg (6,000 U) of polymyxin B/kg was given IV and blood samples were collected for 24 hours. In study 2, 1 mg of polymyxin B/kg was given IV every 8 hours for 5 treatments and blood samples were collected until 24 hours after the last dose. Polymyxin B concentration was measured as the ability to suppress nitrite production by murine macrophages stimulated with lipopolysaccharide and interferon-alpha. Urine was collected prior to the first drug infusion and 24 hours after the fifth drug infusion for determination of urinary gamma-glutamyl transferase (GGT)-to-creatinine ratios. RESULTS In study 1, mean +/- SEM maximal serum polymyxin B concentration was 2.93 +/- 0.38 microg/mL. Polymyxin B was undetectable 18 hours after infusion. In study 2, maximal polymyxin B concentrations after the first and fifth doses were 2.98 +/- 0.81 microg/mL and 1.91 +/- 0.50 microg/mL, respectively. Mean trough concentration for all doses was 0.22 +/- 0.01 microg/mL. A significant effect of repeated administration on peak and trough serum concentration was not detected. Urine GGT-to-creatinine ratios were not affected by polymyxin B administration. CONCLUSIONS AND CLINICAL RELEVANCE Polymyxin B given as multiple infusions to healthy horses by use of this protocol did not accumulate in the vascular compartment and appeared safe. Results support repeated IV use of 1 mg of polymyxin B/kg at 8-hour intervals as treatment for endotoxemia.
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Affiliation(s)
- Peter R Morresey
- Department of Large Animal Clinical Sciences, College of Veterinary Medicine, University of Florida, Gainesville, FL 32610, USA
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Nakamura T, Kawagoe Y, Ueda Y, Koide H. Polymyxin B???Immobilized Fiber Hemoperfusion with Low Priming Volume in an Elderly Septic Shock Patient with Marked Endotoxemia. ASAIO J 2005; 51:482-4. [PMID: 16156319 DOI: 10.1097/01.mat.0000169114.30787.0f] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022] Open
Abstract
An 84-year-old woman with septic shock caused by pyelonephritis is described herein. She was admitted for severe back pain and high fever. Her white blood cell (WBC) count and C-reactive protein (CRP) and endotoxin levels were elevated at 38,000/microl, 40.0 mg/dl, and 8,400 pg/ml, respectively. Her blood pressure was 80/34 mm Hg. Urinalysis revealed occult blood with innumerable WBCs. Plain abdominal radiography showed calcium stones in both kidneys. Septic shock with endotoxemia was diagnosed, and the patient was treated with antibiotics, gamma-globulin, and dopamine. However, her plasma endotoxin level remained high for 3 days. We performed direct hemoperfusion twice using a polymyxin B-immobilized fiber (PMX-F) column with a low priming volume. After PMX-F treatment, the patient's temperature decreased to 36.8 degrees C; her WBC count and CRP level decreased to 9,200/microl and 3.8 mg/dl, respectively. Her plasma endotoxin level decreased to 840 pg/ml after the first treatment and to 188 pg/ml after the second treatment. The next day, her blood endotoxin level further decreased to 32 pg/ml. Her blood pressure increased to 92/60 mm Hg after the first treatment and to 118/76 mm Hg after the second treatment. The patient was discharged on day 26 after admission. Our experience in this case suggests that PMX-F treatment with a low priming volume may be beneficial in elderly patients with septic shock and marked endotoxemia.
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Affiliation(s)
- Tsukasa Nakamura
- Department of Medicine, Shinmatsudo Central General Hospital, Chiba, Japan
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Nakamura T, Kawagoe Y, Matsuda T, Ueda Y, Koide H. Effects of polymyxin B immobilized fiber on urinary N-acetyl-beta-glucosaminidase in patients with severe sepsis. ASAIO J 2005; 50:563-7. [PMID: 15672789 DOI: 10.1097/01.mat.0000142875.62592.3a] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022] Open
Abstract
Severe sepsis is known to cause multiple organ failure, including renal dysfunction. During sepsis, endotoxin targets the renal proximal tubular cells, the function of which can be evaluated on the basis of urinary N-acetyl-beta-glucosaminidase (NAG). We investigated whether urinary NAG activity is altered in patients with severe sepsis and whether treatment with polymyxin B immobilized fibers (PMX-F) affects this activity. Subjects of this study were 120 patients with severe sepsis and 60 healthy volunteers matched for age and gender. Patients were randomly assigned to one of two treatments: PMX-F treatment (n = 70) or conventional treatment (n = 50). The plasma endotoxin level was significantly reduced, from 34.6 +/- 10.2 to 6.8 +/- 2.4 pg/ml (p < 0.01) in patients treated with PMX-F, and the urinary NAG/creatinine ratio was reduced from 46.5 +/- 26.8 U/gm to 18.6 +/- 13.6 U/gm (p < 0.01). The plasma endotoxin level and urinary NAG/creatinine ratio were unchanged in patients who received conventional treatment. The increased urinary NAG/creatinine ratio in patients with severe sepsis may reflect proximal tubular dysfunction. PMX-F is effective in reducing proximal tubular dysfunction, in part owing to reduced plasma endotoxin levels.
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Affiliation(s)
- Tsukasa Nakamura
- Department of Medicine, Shinmatsudo Central General Hospital, Chiba, Japan
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Yuan Z, Yu M, Li J, Hou G, Wang H. Endotoxin adsorbent using dimethylamine ligands. Biomaterials 2005; 26:2741-7. [PMID: 15585278 DOI: 10.1016/j.biomaterials.2004.07.027] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/05/2004] [Accepted: 07/07/2004] [Indexed: 11/30/2022]
Abstract
Various adsorbents have been investigated for removing endotoxin from protein solutions. It is believed that electrostatic interaction and hydrophobic intermolecular interaction are the main interactions in adsorption of endotoxin. In this work, a series of novel molecular recognition adsorbents for removal of endotoxin with dimethylamine ligand were prepared by coupling ligands on polymethyl methacrylate. We found that its adsorption capacity of endotoxin increased almost 8 times in the presence of a hydroxyl group at beta-site of ligand. The computer simulation showed that the hydroxyl group at beta-site could form H bond with endotoxin, as a result an octatomic ring was formed. The spacer in adsorbent and the long alkyl chain in endotoxin were located at the same side of the octatomic ring. In this situation, electrostatic interaction, H bond, cooperative effect of octatomic ring and hydrophobic intermolecular interaction effected simultaneously. The combination of endotoxin with adsorbent was tight and adsorption capacity was effectually increased.
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Affiliation(s)
- Zhi Yuan
- The State Key Laboratory of Functional Polymer Materials for Adsorption and Separation, Institute of Polymer Chemistry, Nankai University, Tianjin 300071, Pepole's Republic of China.
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Nakamura T, Kawagoe Y, Matsuda T, Ebihara I, Koide H. Effects of polymyxin B-immobilized fiber hemoperfusion on amino acid imbalance in septic encephalopathy. Blood Purif 2004; 21:282-6. [PMID: 12944727 DOI: 10.1159/000072546] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 05/20/2003] [Indexed: 11/19/2022]
Abstract
BACKGROUND Septic encephalopathy is a common term denoting the signs of progressing central nervous system dysfunction in septic patients. Metabolic alterations including amino acid imbalance are involved in the pathogenesis of septic encephalopathy. The aim of the present study was to determine whether the ratio of branched-chain amino acids to aromatic amino acids is altered in patients with septic encephalopathy and whether polymyxin B-immobilized fiber (PMX-F) hemoperfusion affects this balance. METHODS 16 septic patients with encephalopathy, 10 septic patients without encephalopathy, and 20 healthy controls were included in this study. Sepsis was diagnosed according to the ACCP/SCCM Consensus Conference criteria. Plasma endotoxin levels, interleukin-6 (IL-6) levels, and amino acid ratios were measured before and after PMX-F treatment. RESULTS Within 12 h of the onset of septic encephalopathy, plasma endotoxin and IL-6 levels were increased significantly in septic patients with encephalopathy in comparison to those in septic patients without encephalopathy (endotoxin, p < 0.05; IL-6, p < 0.01) and those in healthy controls (endotoxin; p < 0.001; IL-6, p < 0.001). The ratio of branched-chain amino acids to aromatic amino acids in septic patients with encephalopathy was decreased in comparison to the ratio in septic patients without encephalopathy (p < 0.05) and that in healthy controls (p < 0.01). PMX-F treatment reduced plasma endotoxin (p < 0.01) and IL-6 levels (p < 0.01) and increased the ratio of branched-chain amino acids to aromatic amino acids (p < 0.01). CONCLUSION The amino acid imbalance in patients with septic encephalopathy may be a marker for the severity of the septic syndrome, and PMX-F hemoperfusion is effective in ameliorating the increased plasma endotoxin and IL-6 levels and the amino acid imbalance in these patients.
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Affiliation(s)
- Tsukasa Nakamura
- Department of Medicine, Shinmatsudo Central General Hospital, Chiba, Japan
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Andersen SK, Gjedsted J, Christiansen C, Tønnesen E. The roles of insulin and hyperglycemia in sepsis pathogenesis. J Leukoc Biol 2003; 75:413-21. [PMID: 14657207 DOI: 10.1189/jlb.0503195] [Citation(s) in RCA: 73] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/08/2023] Open
Abstract
Hyperglycemia is a risk marker of morbidity and mortality in acute critical illness, and insulin therapy seems to be beneficial in this patient group. Whether this is true for a population of sepsis patients, as such, has not been investigated in clinical trials, but evidence from in vitro studies and experimental sepsis suggests that this may be the case. The endocrinology of septic patients is characterized by a shift in the balance between insulin and its counter-regulatory hormones favoring the latter. This leads to prominent metabolic derangements composed of high release and low use of glucose, amino acids, and free fatty acids (FFA), resulting in increased blood levels of these substrates. Circulating, proinflammatory mediators further enhance this state of global catabolism. Increased levels of glucose and FFA have distinct effects on inflammatory signaling leading to additional release of proinflammatory mediators and endothelial and neutrophil dysfunction. Insulin has the inherent capability to counteract the metabolic changes observed in septic patients. Concomitantly, insulin therapy may act as a modulator of inflammatory pathways inhibiting the unspecific, inflammatory activation caused by metabolic substrates. Given these properties, insulin could conceivably be serving a dual purpose for the benefit of septic patients.
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Affiliation(s)
- Soren Kaeseler Andersen
- Department of Anesthesiology and Intensive Care, Institute of Experimental Clinical Research, Aarhus University Hospital, Denmark.
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Shimomura H, Matsuura M, Saito S, Hirai Y, Isshiki Y, Kawahara K. Unusual interaction of a lipopolysaccharide isolated from Burkholderia cepacia with polymyxin B. Infect Immun 2003; 71:5225-30. [PMID: 12933868 PMCID: PMC187347 DOI: 10.1128/iai.71.9.5225-5230.2003] [Citation(s) in RCA: 17] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/21/2003] [Revised: 05/13/2003] [Accepted: 06/06/2003] [Indexed: 11/20/2022] Open
Abstract
We have demonstrated that lipopolysaccharide (LPS) obtained from Burkholderia cepacia, an important opportunistic pathogen, has unique characteristics in both structure and activity. One of the structural characteristics is that the B. cepacia LPS has 4-amino-4-deoxy-L-arabinose (Ara4N) in its inner core region. Polymyxin B (PmxB) is known to act as an LPS antagonist, but LPS with Ara4N is suggested to be PmxB resistant by decreasing the binding capability of PmxB. Interaction of B. cepacia LPS with PmxB was investigated and compared with that of a reference LPS of Salmonella enterica serovar Abortusequi, referred to hereafter as the reference LPS. B. cepacia LPS suffered no suppressive effect of PmxB in its activity to stimulate murine peritoneal macrophages for induction of tumor necrosis factor alpha (TNF-alpha) and IL-6 even when the activity of the reference LPS was completely suppressed. A characteristic of B. cepacia LPS is that it has selectively weak interleukin-1 beta (IL-1 beta)-inducing activity while activity to induce TNF-alpha and IL-6 has been shown to be as strong as that of the reference LPS. Remarkably, PmxB augmented the IL-1 beta-inducing activity of B. cepacia LPS to the level of that of the reference LPS and, in contrast, completely suppressed the strong activity of the reference LPS. Using PmxB-immobilized beads, the adsorbances of these LPSs to the beads were compared, and it was found that B. cepacia LPS bound to PmxB with a high affinity similar to that of the reference LPS. These results indicate an unusual interaction of B. cepacia LPS with PmxB whereby B. cepacia LPS not only allows the binding of PmxB with high affinity, even though it contains Ara4N, but also suffers no suppressive effect of PmxB on its activity. Moreover, a remarkable increase in its IL-1 beta-inducing activity was also observed.
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Affiliation(s)
- Hirofumi Shimomura
- Division of Bacteriology, Department of Infection and Immunity, Jichi Medical School, Tochigi 239-0498, Japan
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