Safety and efficacy of long-term mild hypothermia for severe traumatic brain injury with refractory intracranial hypertension (LTH-1): A multicenter randomized controlled trial

Jiyuan Hui; Junfeng Feng; Yue Tu; Weituo Zhang; Chunlong Zhong; Min Liu; Yuhai Wang; Liansheng Long; Ligang Chen; Jinfang Liu; Chaohui Mou; Binghui Qiu; Xianjian Huang; Qibing Huang; Nu Zhang; Xiaofeng Yang; Chaohua Yang; Lihong Li; Rong Ma; Xiang Wu; Jin Lei; Yong Jiang; Liang Liu; Guoyi Gao; Jiyao Jiang; LTH-1 Trial collaborators

doi:10.1016/j.eclinm.2021.100732

Safety and efficacy of long-term mild hypothermia for severe traumatic brain injury with refractory intracranial hypertension (LTH-1): A multicenter randomized controlled trial

EClinicalMedicine. 2021 Jan 28:32:100732. doi: 10.1016/j.eclinm.2021.100732. eCollection 2021 Feb.

Authors

Jiyuan Hui¹, Junfeng Feng¹, Yue Tu², Weituo Zhang³, Chunlong Zhong⁴, Min Liu⁴, Yuhai Wang⁵, Liansheng Long⁶, Ligang Chen⁷, Jinfang Liu⁸, Chaohui Mou⁹, Binghui Qiu¹⁰, Xianjian Huang¹¹, Qibing Huang¹², Nu Zhang¹³, Xiaofeng Yang¹⁴, Chaohua Yang¹⁵, Lihong Li¹⁶, Rong Ma¹, Xiang Wu¹, Jin Lei¹, Yong Jiang⁷, Liang Liu⁷, Guoyi Gao¹⁷, Jiyao Jiang^{1

11

14}; LTH-1 Trial collaborators

Affiliations

¹ Head Trauma Center, Department of Neurosurgery, Renji Hospital, Shanghai Jiao Tong University/School of Medicine, Shanghai Institute of Head Trauma, Shanghai, China.
² Neurological Intensive Care Unit, Beijing Chaoyang Integrative Medicine Emergency Medical Center, Beijing, China.
³ Clinical Research Institute, Shanghai Jiao Tong University/School of Medicine, Shanghai, China.
⁴ Department of Neurosurgery, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, China.
⁵ Department of Neurosurgery, Taihu Hospital, Wuxi, China.
⁶ Department of Neurosurgery, South Taihu Hospital, Huzhou, China.
⁷ Department of Neurosurgery, The Affiliated Hospital of Southwest Medical University, Luzhou, China.
⁸ Department of Neurosurgery, Xiangya Hospital, Central South University, Changsha, China.
⁹ Department of Neurosurgery, Taizhou First People's Hospital, Zhejiang, China.
¹⁰ Department of Neurosurgery, Nanfang Hospital, Southern Medical University, Guangzhou, China.
¹¹ Department of Neurosurgery, Shenzhen Second People's Hospital, Shenzhen, China.
¹² Department of Neurosurgery, Qilu Hospital of Shandong University, Jinan, China.
¹³ Department of Neurosurgery, The Second Affiliated Hospital of Wenzhou Medical University, Wenzhou, China.
¹⁴ Emergency and Trauma Center, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China.
¹⁵ Department of Neurosurgery, West China Hospital of Sichuan University, Chengdu, China.
¹⁶ Department of Neurosurgery, Tangdu Hospital, Xi'an, China.
¹⁷ Department of Neurosurgery, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

Abstract

Background: Therapeutic hypothermia may need prolonged duration for the patients with severe traumatic brain injury (sTBI).

Methods: The Long-Term Hypothermia trial was a prospective, multicenter, randomized, controlled clinical trial to examine the safety and efficacy in adults with sTBI. Eligible patients were 18-65, Glasgow Coma Scale score at 4 to 8, and initial intracranial pressure (ICP) ≥ 25 mm Hg, randomly assigned to the long-term mild hypothermia group (34-35 °C for 5 days) or normothermia group at 37 °C. The primary outcome was the Glasgow outcome scale (GOS) at 6 months. Secondary outcomes included ICP control, complications and laboratory findings, the length of ICU and hospital stay, and GOS at 6 months in patients with initial ICP ≥ 30 mm Hg. This trial is registered with ClinicalTrials.gov, NCT01886222.

Findings: 302 patients were enrolled from June 25, 2013, to December 31, 2018, with 6 months follow-up in 14 hospitals, 156 in hypothermia group and 146 in normothermia group. There was no difference in favorable outcome (OR 1·55, 95%CI 0·91-2·64; P = 0·105) and in mortality (P = 0·111) between groups. In patients with an initial ICP ≥ 30 mm Hg, hypothermic treatment significantly increased favorable outcome over normothermia group (60·82%, 42·71%, respectively; OR 1·861, 95%CI 1·031-3·361; P = 0·039). Long-term mild hypothermia did not increase the incidences of complications.

Interpretation: Long-term mild hypothermia did not improve the neurological outcomes. However, it may be a potential option in sTBI patients with initial ICP ≥ 30 mm Hg.

Funding: : Shanghai municipal government and Shanghai Jiao Tong University/School of Medicine.

Keywords: Efficacy; Prolonged hypothermia; Randomized controlled trial; Safety; Traumatic brain injury.

Associated data

ClinicalTrials.gov/NCT01886222