Initial Blood Ammonia Level Is a Useful Prognostication Tool in Out-Of-Hospital Cardiac Arrest ― Multicenter Prospective Study (SOS-KANTO 2012 Study) ―

Advance Publication by-J-STAGE

Circ J Supplementary File doi: 10.1253/circj.CJ-17-0335

Initial Blood Ammonia Level Is a Useful Prognostication Tool in Out-of-Hospital Cardiac Arrest ― Multicenter Prospective Study (SOS-KANTO 2012 Study) ―

SOS-KANTO 2012 Study Group

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Appendix S1. SOS-KANTO 2012 Investigators (Naoto Morimura, MD); National Hospital Organization Yokohama SOS-KANTO 2012 Study Group Medical Center (Ryosuke Furuya, MD); National Disaster Medical Koichiro Shinozaki (Feinstein Institute for Medical Research, Center (Yuichi Koido, MD); Yamanashi Prefectural Central Hospital Manhasset, NY, USA), Masaru Suzuki (Keio University, Tokyo, (Fumiaki Iwase, MD); Surugadai Nihon University Hospital (Ken Japan), Shigeto Oda (Chiba University, Chiba, Japan), Lance B. Nagao, MD); Yokohama Rosai Hospital (Shigeru Kanesaka, MD); Becker (Feinstein Institute for Medical Research, Manhasset, NY, Showa General Hospital (Yasusei Okada, MD); Nippon Medical USA), Takashi Tagami (Nippon Medical School Tama Nagayama School Tamanagayama Hospital (Kyoko Unemoto, MD); Tokyo Hospital, Tokyo, Japan), Atsushi Sakurai (Nihon University, Tokyo, Women’s Medical University Yachiyo Medical Center (Tomohito Japan), Yoshio Tahara (National Cerebral and Cardiovascular Center, Sadahiro, MD); Awa Regional Medical Center (Masayuki Iyanaga, Osaka, Japan), Ken Nagao (Nihon University Surugadai Hospital, MD); Todachuo General Hospital (Asaki Muraoka, MD); Japanese Tokyo, Japan), Naohiro Yonemoto (National Center of Neurology Red Cross Medical Center (Munehiro Hayashi, MD); St. Luke’s and Psychiatry, Tokyo, Japan), Arino Yaguchi (Tokyo Women’s International Hospital (Shinichi Ishimatsu, MD); Showa University Medical University Hospital, Tokyo, Japan), and Naoto Morimura School of Medicine (Yasufumi Miyake, MD); Totsuka Kyoritsu (Yokohama City University, Yokohama, Japan). Hospital (Hideo Yokokawa, MD); St. Marianna University School of Medicine (Yasuaki Koyama, MD); National Hospital Organization SOS-KANTO 2012 Steering Council Mito Medical Center (Asuka Tsuchiya, MD); Tokyo Metropolitan Yokohama City University Medical Center, Kanagawa (President, Tama Medical Center (Tetsuya Kashiyama, MD); Showa University Naoto Morimura, MD); Nihon University School of Medicine, Fujigaoka Hospital (Munetaka Hayashi, MD); Gunma University Tokyo (Director, Atsushi Sakurai, MD); National Cerebral and Graduate School of Medicine (Kiyohiro Oshima, MD); Saitama Red Cardiovascular Center Hospital, Osaka (Director, Yoshio Tahara, Cross Hospital (Kazuya Kiyota, MD); Tokyo Metropolitan Bokutoh MD); Tokyo Women’s Medical University Hospital, Tokyo (Arino Hospital (Yuichi Hamabe, MD); Nippon Medical School Hospital Yaguchi, MD); Nihon University Surugadai Hospital, Tokyo (Ken (Hiroyuki Yokota, MD); Keio University Hospital (Shingo Hori, Nagao, MD); Nippon Medical School Hospital, Tokyo (Tagami MD); Chiba Emergency Medical Center (Shin Inaba, MD); Teikyo Takashi, MD); Japanese Red Cross Maebashi Hospital, Gunma (Dai University School of Medicine (Tetsuya Sakamoto, MD); Japanese Miyazaki, MD); National Disaster Medical Center, Tokyo (Tomoko Red Cross Musashino Hospital (Naoshige Harada, MD); National Ogasawara, MD); Keio University Hospital, Tokyo (Kei Hayashida, Center for Global Health and Medicine Hospital (Akio Kimura, MD, Masaru Suzuki, MD); Tokai University School of Medicine, MD); Tokyo Metropolitan Police Hospital (Masayuki Kanai, MD); Kanagawa (Mari Amino, MD); Kimitsu Chuo Hospital, Chiba Medical Hospital of Tokyo Medical and Dental University (Yasuhiro (Nobuya Kitamura, MD); Juntendo University Nerima Hospital, Otomo, MD); Juntendo University Nerima Hospital (Manabu Sugita, Tokyo (Tomohisa Nomura, MD); Tokyo Metropolitan Children’s MD); Nihon University School of Medicine (Kosaku Kinoshita, MD); Medical Centre, Tokyo (Naoki Shimizu, MD); Tokyo Metropolitan Toho University Ohashi Medical Center (Takatoshi Sakurai, MD); Bokutoh Hospital, Tokyo (Akiko Akashi, MD), National Center of Saiseikai Yokohamashi Tobu Hospital (Mitsuhide Kitano, MD); Neurology and Psychiatry, Tokyo, Japan (Naohiro Yonemoto, DPH). Nippon Medical School Musashikosugi Hospital (Kiyoshi Matsuda, MD); Tokyo Rosai Hospital (Kotaro Tanaka, MD); Toho University SOS-KANTO 2012 Study Group Participating Investigators Omori Medical Center (Katsunori Yoshihara, MD); Hiratsuka City Tokai University School of Medicine (Sadaki Inokuchi, MD); Hospital (Kikuo Yoh, MD); Yokosuka Kyosai Hospital (Junichi Yokohama Seibu Hospital (Yoshihiro Masui, MD); Koto Hospital Suzuki, MD); Saiseikai Yokohamashi Nambu Hospital (Hiroshi (Kunihisa Miura, MD); Saitama Medical Center Advanced Tertiary Toyoda, MD); Nippon Medical School Chiba Hokusoh Hospital Medical Center (Haruhiko Tsutsumi, MD); Kawasaki Municipal (Kunihiro Mashiko, MD); Tokyo Metropolitan Children’s Medical Hospital Emergency and Critical Care Center (Kiyotsugu Takuma, Centre (Naoki Shimizu, MD); National Medical Center for Children MD); Yokohama Municipal Citizen’s Hospital (Ishihara Atsushi, and Mothers (Takashi Muguruma, MD); Chiba Aoba Municipal MD); Japanese Red Cross Maebashi Hospital (Minoru Nakano, Hospital (Tadanaga Shimada, MD); Kuki General Hospital (Yoshiro MD); Juntendo University Urayasu Hospital (Hiroshi Tanaka, MD); Kobe, MD); Matsudo City Hospital (Tomohisa Shoko, MD); Japanese Dokkyo Medical University Koshigaya Hospital (Keiichi Ikegami, Red Cross Narita Hospital (Kazuya Nakanishi, MD); Tokyo Bay MD); Hachioji Medical Center of Tokyo Medical University (Takao Urayasu/Ichikawa Medical Center (Takashi Shiga, MD); NTT Medical Arai, MD); Tokyo Women’s Medical University Hospital (Arino Center Tokyo (Takefumi Yamamoto, MD); Tokyo Saiseikai Central Yaguchi, MD); Kimitsu Chuo Hospital (Nobuya Kitamura, MD); Hospital (Kazuhiko Sekine, MD); Fuji Heavy Industries Health Chiba University Graduate School of Medicine (Shigeto Oda, MD); Insurance Society OTA Memorial Hospital (Shinichi Izuka, MD). Saiseikai Utsunomiya Hospital (Kenji Kobayashi, MD); Mito Saiseikai (http://www.jaam- kanto.jp/sos_kanto/sos_kanto2012_contributors. General Hospital (Takayuki Suda, MD); Dokkyo Medical University html) (Kazuyuki Ono, MD); Yokohama City University Medical Center Advance Publication by-J-STAGE

Figure S1. Median (IQR) blood ammonia and lactate level differed significantly with regard to neurological outcome (P<0.001, P<0.001, respectively).

Table S1. Subject Characteristics vs. Biomarker Data Status Patients with admission (n=3,011) Total (n=16,452) Valid Missing Valid Missing P-value P-value (n=991) (n=2,020) (n=4,542) (n=11,910) Baseline characteristics Age (years) 71 (60–81) 70 (60–81) 0.817 75 (62–83) 74 (61–83) 0.152 Male 656 (66) 1,304 (65) 0.375 2,828 (62) 7,135 (60) 0.006 Cardiac origin 471 (48) 1,019 (50) 0.132 2,017 (45) 5,687 (50) <0.001 CA in an EMS vehicle 49 (4.9) 80 (4.0) 0.210 100 (2) 247 (2) 0.597 Bystander witnessed 655 (66) 1,340 (67) 0.839 2,325 (52) 5,408 (46) <0.001 Bystander CPR 418 (42) 834 (41) 0.624 1,681 (38) 3,906 (33) <0.001 First ECG as shockable rhythm 176 (18) 360 (19) 0.964 378 (9) 784 (7) <0.001 Call receipt to ED arrival (min) 32 (26–39) 33 (27–41) 0.001 33 (27–40) 33 (27–41) 0.107 Outcomes ROSC – – – 1,755 (39) 3,485 (30) <0.001 Hospital admission – – – 1,091 (26) 2,304 (23) <0.001 Favorable neurological outcome 130 (14) 250 (14) 0.660 148 (3.3) 308 (2.7) 0.020 Data given as n (%) or median (IQR). CA, cardiac arrest; CPR, cardiopulmonary resuscitation; ECG, electrocardiogram; ED, emergency department; EMS, emergency medical services; ROSC, return of spontaneous circulation; shockable rhythm, first ECG exhibiting ventricular fibrillation or pulseless ventricular tachycardia.

Table S2. Predictive Accuracy of Lactate and Ammonia for Favorable Neurological Outcome† Ammonia ≤100 μmol/L‡ Lactate ≤12 mmol/L‡ Favorable neurological outcome (n=130) 111 (85) 112 (86) Poor neurological outcome (n=782) 366 (47) 423 (54) OR (95% CI) 6.64 (4.00–11.02) 5.28 (3.15–8.86) AUC (95% CI) 0.80 (0.76–0.84) 0.77 (0.72–0.82) P-value <0.001 <0.001 Data given as n (%). †Of 991 patients, 79 were missing data on neurological outcome. AUC, area under the curve. ‡Determined in the previous report.S1

Reference S1. Shinozaki K, Oda S, Sadahiro T, Nakamura M, Hirayama Y, Watanabe E, et al. Blood ammonia and lactate levels on hospital arrival as a predictive biomarker in patients with out-of-hospital cardiac arrest. Resuscitation 2011; 82: 404 – 409.