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Impact of Body Temperature Abnormalities on the Implementation of Sepsis Bundles and Outcomes in Patients With Severe Sepsis

A Retrospective Sub-Analysis of the Focused Outcome Research on Emergency Care for Acute Respiratory Distress Syndrome, Sepsis and Trauma Study

Kushimoto, Shigeki, MD, PhD1; Abe, Toshikazu, MD, PhD2,3; Ogura, Hiroshi, MD, PhD4; Shiraishi, Atsushi, MD, PhD5; Saitoh, Daizoh, MD, PhD6; Fujishima, Seitaro, MD, PhD7; Mayumi, Toshihiko, MD, PhD8; Hifumi, Toru, MD, PhD9; Shiino, Yasukazu, MD, PhD10; Nakada, Taka-aki, MD, PhD11; Tarui, Takehiko, MD, PhD12; Otomo, Yasuhiro, MD, PhD13; Okamoto, Kohji, MD, PhD14; Umemura, Yutaka, MD, PhD4; Kotani, Joji, MD, PhD15; Sakamoto, Yuichiro, MD, PhD16; Sasaki, Junichi, MD, PhD17; Shiraishi, Shin-ichiro, MD, PhD18; Takuma, Kiyotsugu, MD, PhD19; Tsuruta, Ryosuke, MD, PhD20; Hagiwara, Akiyoshi, MD, PhD21; Yamakawa, Kazuma, MD, PhD22; Masuno, Tomohiko, MD, PhD23; Takeyama, Naoshi, MD, PhD24; Yamashita, Norio, MD, PhD25; Ikeda, Hiroto, MD, PhD26; Ueyama, Masashi, MD, PhD27; Fujimi, Satoshi, MD, PhD22; Gando, Satoshi, MD, PhD28 on behalf of JAAM Focused Outcome Research on Emergency Care for Acute respiratory distress syndrome, Sepsis and Trauma (FORECAST) Group

doi: 10.1097/CCM.0000000000003688
Clinical Investigations

Objectives: To investigate the impact of body temperature on disease severity, implementation of sepsis bundles, and outcomes in severe sepsis patients.

Design: Retrospective sub-analysis.

Setting: Fifty-nine ICUs in Japan, from January 2016 to March 2017.

Patients: Adult patients with severe sepsis based on Sepsis-2 were enrolled and divided into three categories (body temperature < 36°C, 36–38°C, > 38°C), using the core body temperature at ICU admission.

Interventions: None.

Measurements and Main Results: Compliance with the bundles proposed in the Surviving Sepsis Campaign Guidelines 2012, in-hospital mortality, disposition after discharge, and the number of ICU and ventilator-free days were evaluated. Of 1,143 enrolled patients, 127, 565, and 451 were categorized as having body temperature less than 36°C, 36–38°C, and greater than 38°C, respectively. Hypothermiabody temperature less than 36°C—was observed in 11.1% of patients. Patients with hypothermia were significantly older than those with a body temperature of 36–38°C or greater than 38°C and had a lower body mass index and higher prevalence of septic shock than those with body temperature greater than 38°C. Acute Physiology and Chronic Health Evaluation II and Sequential Organ Failure Assessment scores on the day of enrollment were also significantly higher in hypothermia patients. Implementation rates of the entire 3-hour bundle and administration of broad-spectrum antibiotics significantly differed across categories; implementation rates were significantly lower in patients with body temperature less than 36°C than in those with body temperature greater than 38°C. Implementation rate of the entire 3-hour resuscitation bundle + vasopressor use + remeasured lactate significantly differed across categories, as did the in-hospital and 28-day mortality. The odds ratio for in-hospital mortality relative to the reference range of body temperature greater than 38°C was 1.760 (95% CI, 1.134–2.732) in the group with hypothermia. The proportions of ICU-free and ventilator-free days also significantly differed between categories and were significantly smaller in patients with hypothermia.

Conclusions: Hypothermia was associated with a significantly higher disease severity, mortality risk, and lower implementation of sepsis bundles.

1Division of Emergency and Critical Care Medicine, Tohoku University Graduate School of Medicine, Sendai, Japan.

2Department of General Medicine, Juntendo University, Tokyo, Japan.

3Health Services Research and Development Center, University of Tsukuba, Tsukuba, Japan.

4Department of Traumatology and Acute Critical Medicine, Osaka University Graduate School of Medicine, Osaka, Japan.

5Emergency and Trauma Center, Kameda Medical Center, Kamogawa, Japan.

6Division of Traumatology, Research Institute, National Defense Medical College, Tokorozawa, Japan.

7Center for General Medicine Education, Keio University School of Medicine, Tokyo, Japan.

8Department of Emergency Medicine, School of Medicine, University of Occupational and Environmental Health, Kitakyushu, Japan.

9Department of Emergency and Critical Care Medicine, St. Luke’s International Hospital, Tokyo, Japan.

10Department of Acute Medicine, Kawasaki Medical School, Kurashiki, Japan.

11Department of Emergency and Critical Care Medicine, Chiba University Graduate School of Medicine, Chiba, Japan.

12Department of Trauma and Critical Care Medicine, Kyorin University School of Medicine, Mitaka, Japan.

13Trauma and Acute Critical Care Center, Medical Hospital, Tokyo Medical and Dental University, Tokyo, Japan.

14Department of Surgery, Center for Gastroenterology and Liver Disease, Kitakyushu City Yahata Hospital, Kitakyushu, Japan.

15Department of Disaster and Emergency Medicine, Kobe University Graduate School of Medicine, Kobe, Japan.

16Emergency and Critical Care Medicine, Saga University Hospital, Saga, Japan.

17Department of Emergency and Critical Care Medicine, Keio University School of Medicine, Tokyo, Japan.

18Department of Emergency and Critical Care Medicine, Aizu Chuo Hospital, Aizuwakamatsu, Japan.

19Emergency & Critical Care Center, Kawasaki Municipal Kawasaki Hospital, Kawasaki, Japan.

20Advanced Medical Emergency & Critical Care Center, Yamaguchi University Hospital, Ube, Japan.

21Center Hospital of the National Center for Global Health and Medicine, Tokyo, Japan.

22Division of Trauma and Surgical Critical Care, Osaka General Medical Center, Osaka, Japan.

23Department of Emergency and Critical Care Medicine, Nippon Medical School, Tokyo, Japan.

24Advanced Critical Care Center, Aichi Medical University Hospital, Nagakute, Japan.

25Advanced Emergency Medical Service Center, Kurume University Hospital, Kurume, Japan.

26Department of Emergency Medicine, Teikyo University School of Medicine, Tokyo, Japan.

27Department of Trauma, Critical Care Medicine, and Burn Center, Japan Community Healthcare Organization, Chukyo Hospital, Nagoya, Japan.

28Division of Acute and Critical Care Medicine, Hokkaido University Graduate School of Medicine, Sapporo, Japan.

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Supported, in part, by funds of the Japanese Association for Acute Medicine.

Dr. Gando’s institution received funding from Japan Society for the Promotion of Science (Grant-in-aid for Scientific Research); he received funding from Asahi Kasei Pharma (lecture fee); and he disclosed that this article is supported by the Japanese Association for Acute Medicine. The remaining authors have disclosed that they do not have any potential conflicts of interest.

Address requests for reprints to: Shigeki Kushimoto, MD, Division of Emergency and Critical Care Medicine, Tohoku University Graduate School of Medicine, 1-1 Seiryo-machi, Aoba-ku, Sendai 980–8574, Japan. E-mail:

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