Vivian L. Smith Center for Neurologic Research, Department of Neurosurgery, The University of Texas Medical School at Houston, Houston, TX, USA.
J Neurosurg. 2012 Oct;117(4):714-20. doi: 10.3171/2012.6.JNS111690. Epub 2012 Jul 27.
The authors hypothesized that cooling before evacuation of traumatic intracranial hematomas protects the brain from reperfusion injury and, if so, further hypothesized that hypothermia induction before or soon after craniotomy should be associated with improved outcomes.
The National Acute Brain Injury Study: Hypothermia I (NABIS:H I) was a randomized multicenter clinical trial of 392 patients with severe brain injury treated using normothermia or hypothermia for 48 hours with patients reaching 33°C at 8.4 ± 3 hours after injury. The National Acute Brain Injury Study: Hypothermia II (NABIS:H II) was a randomized, multicenter clinical trial of 97 patients with severe brain injury treated with normothermia or hypothermia for 48 hours with patients reaching 35°C within 2.6 ± 1.2 hours and 33°C within 4.4 ± 1.5 hours of injury. Entry and exclusion criteria, management, and outcome measures in the 2 trials were similar.
In NABIS:H II among the patients with evacuated intracranial hematomas, outcome was poor (severe disability, vegetative state, or death) in 5 of 15 patients in the hypothermia group and in 9 of 13 patients in the normothermia group (relative risk 0.44, 95% CI 0.22-0.88; p = 0.02). All patients randomized to hypothermia reached 35°C within 1.5 hours after surgery start and 33°C within 5.55 hours. Applying these criteria to NABIS:H I, 31 of 54 hypothermia-treated patients reached a temperature of 35°C or lower within 1.5 hours after surgery start time, and the remaining 23 patients reached 35°C at later time points. Outcome was poor in 14 (45%) of 31 patients reaching 35°C within 1.5 hours of surgery, in 14 (61%) of 23 patients reaching 35°C more than 1.5 hours of surgery, and in 35 (60%) of 58 patients in the normothermia group (relative risk 0.74, 95%, CI 0.49-1.13; p = 0.16). A meta-analysis of 46 patients with hematomas in both trials who reached 35°C within 1.5 hours of surgery start showed a significantly reduced rate of poor outcomes (41%) compared with 94 patients treated with hypothermia who did not reach 35°C within that time and patients treated at normothermia (62%, p = 0.009).
Induction of hypothermia to 35°C before or soon after craniotomy with maintenance at 33°C for 48 hours thereafter may improve outcome of patients with hematomas and severe traumatic brain injury. Clinical trial registration no.: NCT00178711.
作者假设创伤性颅内血肿清除前的冷却可以保护大脑免受再灌注损伤，如果是这样，进一步假设开颅前或开颅后不久诱导低温应与改善结果相关。
国家急性脑损伤研究：低温 I（NABIS：H I）是一项对使用正常体温或低温治疗的 392 例严重脑损伤患者进行的随机多中心临床试验，患者在损伤后 8.4 ± 3 小时达到 33°C。国家急性脑损伤研究：低温 II（NABIS：H II）是一项对 97 例严重脑损伤患者进行的随机、多中心临床试验，采用正常体温或低温治疗 48 小时，患者在损伤后 2.6 ± 1.2 小时内达到 35°C，4.4 ± 1.5 小时内达到 33°C。这两项试验的入组和排除标准、治疗和预后评估均相似。
在 NABIS：H II 中，在有颅内血肿清除的患者中，低温组的 15 例患者中有 5 例（严重残疾、植物状态或死亡），而常规治疗组的 13 例患者中有 9 例（相对风险 0.44，95%CI 0.22-0.88；p=0.02）。所有随机接受低温治疗的患者在手术开始后 1.5 小时内达到 35°C，5.55 小时内达到 33°C。将这些标准应用于 NABIS：H I，54 例接受低温治疗的患者中有 31 例在手术开始后 1.5 小时内达到 35°C 或更低，其余 23 例在稍后时间点达到 35°C。在 31 例在手术开始后 1.5 小时内达到 35°C 的患者中，有 14 例（45%）预后不良，在 23 例在手术开始后 1.5 小时以上达到 35°C 的患者中，有 14 例（61%）预后不良，在 58 例常规治疗组患者中，有 35 例（60%）预后不良（相对风险 0.74，95%CI 0.49-1.13；p=0.16）。对两项试验中血肿达到 35°C 的 46 例患者的荟萃分析显示，与未在该时间内达到 35°C 的接受低温治疗的 94 例患者和接受常规治疗的患者（62%，p=0.009）相比，预后不良的发生率显著降低（41%）。
开颅前或开颅后不久诱导低温至 35°C，并随后维持 33°C 48 小时，可能改善血肿和严重创伤性脑损伤患者的预后。临床试验注册号：NCT00178711。
