Department of Neurosurgery, China Medical University Hospital, Taichung, Taiwan, Republic of China.
World Neurosurg. 2010 Dec;74(6):654-60. doi: 10.1016/j.wneu.2010.06.019.
Severe traumatic brain injury (TBI) was to be one of the major health problems encountered in modern medicine and had an incalculable socioeconomic impact. The initial cerebral damage after acute brain injury is often exacerbated by postischemic hyperthermia and worsens the outcome. Hypothermia is one of the current therapies designed to combat this deleterious effect. The brain tissue oxygen (P(ti)o(2))-guided cerebral perfusion pressure (CPP) management was successfully reduced because of cerebral hypoxic episodes following TBI.
Forty-five patients with severe TBI whose Glasgow Coma Scale (GCS) score ranged between 4 and 8 during September 2006 and August 2007 were enrolled in China Medical University Hospital, Taichung, Taiwan. One patient with a GCS score of 3 was excluded for poor outcome. These patients were randomized into three groups. Group A (16 patients) was intracranial pressure/cerebral perfusion pressure (ICP/CPP)-guided management only, Group B (15 patients) was ICP/CPP guided with mild hypothermia, and Group C (14 patients) was combined mild hypothermia and P(ti)o(2) guided with CPP management on patients with severe TBI. All patients were treated with ICP/CPP management (ICP <20 mm Hg, CPP >60 mm Hg). However, the group with P(ti)o(2) monitoring was required to raise the P(ti)o(2) above 20 mm Hg. Length of intensive care unit stay, ICP, P(ti)o(2), Glasgow Outcome Scale (GOS) score, mortality, and complications were analyzed.
The ICP values progressively increased in the first 3 days but showed smaller changes in hypothermia groups (Groups B and C) and were significantly lower than those of the normothermia group (Group A) at the same time point. We also found out that the averaged ICP were significantly related to days and the daily variations [measured as (daily observation - daily group mean)(2)] of ICP were shown to the significantly different among three treatment groups after the third posttraumatic day. The values of P(ti)o(2) in Group C tended to rise when the ICP decreased were also observed. A favorable outcome is divided by the result of GOS scores. The percentage of favorable neurologic outcome was 50% in the normothermia group, 60% in the hypothermia-only group, and 71.4% in the P(ti)o(2) group, with statistical significance. The percentage of mortality was 12.5% in the normothermia group, 6.7% in the hypothermia-only group, and 8.5% in the P(ti)o(2) group, without statistical significance in three groups. Complications included pulmonary infections, peptic ulcer, and leukocytopenia (43.8% in the normothermia group, 55.6% in the hypothermia-only group, and 50% in the P(ti)o(2) group).
Therapeutic mild hypothermia combined with P(ti)o(2)-guided CPP/ICP management allows reducing elevated ICP before 24 hours after injury, and daily variations of ICP were shown to be significantly different among the three treatment groups after the third posttraumatic day. It means that the hypothermia groups may reduce the ICP earlier and inhibit the elicitation of acute inflammation after cerebral contusion. Our data also provided evidence that early treatment that lowers P(ti)o(2) may improve the outcome and seems the best medical treatment method in these three groups. We concluded that therapeutic mild hypothermia combined with P(ti)o(2)-guided CPP/ICP management provides beneficial effects when treating TBI, and a multicenter randomized trial needs to be undertaken.
严重创伤性脑损伤(TBI)是现代医学中遇到的主要健康问题之一,具有不可估量的社会经济影响。急性脑损伤后的初始脑损伤通常会因缺血后发热而加重,并使预后恶化。低温是目前旨在对抗这种有害影响的治疗方法之一。由于 TBI 后出现脑缺氧发作,脑氧(PtiO2)指导的脑灌注压(CPP)管理成功降低。
2006 年 9 月至 2007 年 8 月期间,在中国台湾台中中国医科大学附属医院,共纳入 45 例格拉斯哥昏迷量表(GCS)评分在 4 至 8 分之间的严重 TBI 患者。因预后不良,1 例 GCS 评分 3 分的患者被排除在外。这些患者被随机分为三组。A 组(16 例)为颅内压/脑灌注压(ICP/CPP)指导管理组,B 组(15 例)为 ICP/CPP 指导轻度低温组,C 组(14 例)为 ICP/CPP 指导轻度低温合并 PtiO2 指导 CPP 管理组。所有患者均接受 ICP/CPP 管理(ICP <20mmHg,CPP >60mmHg)。然而,有 PtiO2 监测的组需要将 PtiO2 提高到 20mmHg 以上。分析了重症监护病房停留时间、ICP、PtiO2、格拉斯哥结局量表(GOS)评分、死亡率和并发症。
ICP 值在第 1 至 3 天逐渐升高,但在低温组(B 组和 C 组)中变化较小,在同一时间点明显低于常温组(A 组)。我们还发现,平均 ICP 与天数显著相关,ICP 的每日变化[以(每日观察-每日组均值)(2)表示]在创伤后第 3 天之后在三组治疗组中表现出显著差异。当 ICP 降低时,C 组的 PtiO2 值也趋于升高。根据 GOS 评分结果,预后良好的比例为常温组 50%,单纯低温组 60%,PtiO2 组 71.4%,差异有统计学意义。常温组死亡率为 12.5%,单纯低温组 6.7%,PtiO2 组 8.5%,三组差异无统计学意义。并发症包括肺部感染、消化性溃疡和白细胞减少症(常温组 43.8%,单纯低温组 55.6%,PtiO2 组 50%)。
治疗性轻度低温联合 PtiO2 指导的 CPP/ICP 管理可在损伤后 24 小时内降低升高的 ICP,并且在创伤后第 3 天之后,三组之间的 ICP 每日变化差异显著。这意味着低温组可能更早降低 ICP,并抑制脑挫裂伤后急性炎症的发生。我们的数据还提供了证据,表明早期治疗降低 PtiO2 可能改善预后,并且在这三组中似乎是最佳的治疗方法。我们得出结论,治疗性轻度低温联合 PtiO2 指导的 CPP/ICP 管理对 TBI 治疗有有益的影响,需要进行多中心随机试验。