Asian Case Reports in Emergency Medicine
Vol.05 No.02(2017), Article ID:20627,6 pages
10.12677/ACREM.2017.52004

The Effects of Therapeutic Hypothermia on Changes in Partial Pressure of Brain Tissue Oxygen (PbtO2) Gradients for Patients with Severe Traumatic Brain Injury—Hypothermia on Partial Pressure of Brain Tissue Oxygen

Mingmin Chen1, Haisong Xu2, Peng Zhao1, Wusi Qiu2*, Qizhou Jiang2

1College of Medicine, Hangzhou Normal University, Hangzhou Zhejiang

2Dept. of Neurosurgery, Hangzhou Second Hospital, College of Medicine, Hangzhou Normal University, Hangzhou Zhejiang

Received: May 4th, 2017; accepted: May 18th, 2017; published: May 24th, 2017

ABSTRACT

Objective: To investigate the effects of therapeutic hypothermia on changes in partial pressure of brain tissue oxygen (PbtO2) gradients for patients with severe traumatic brain injury (TBI). Methods: Sixty in-patients with severe TBI after unilateral craniotomy were randomized into a therapeutic hypothermia group with the brain temperature maintained at 33 - 35 degrees Celsius for 5 days using mild hypothermia therapeutic apparatus or cooling blankets, and a normothermia control group in the intensive care unit. The fibres were introduced into the brain parenchyma of the bilateral frontal lobes after general anesthesia, then monitor the PtbO2 of two sides cerebral hemisphere (uninjured side PbtO2-injured side PbtO2). In the meantime, the arterial blood gas analysis, blood pressure, pulse, breath rate, blood oxygen saturation, central venous pressure and intracranial pressure (ICP) were observed and measured during treatment, and the complications (including pulmonary infections, thrombocytopenia defined as platelet count < 100 × 109/L, hemorrhage in the digestive tract, electrolyte disorders and renal malfunction) as well as the Glasgow outcome scale and PbtO2 were evaluated at 6 months after injury. Results: The mean intracranial pressure values and PtbO2 gradient in the therapeutic hypothermia group at 24, 48, and 72 hours after treatment were much lower than those of the control group. There are significant difference between the therapeutic hypothermia group and the control group about the mean good recovery rate and the mortality rates (P < 0.05), and the recovery rate (GOS grades 4 - 5 scores) in the therapeutic hypothermia is much better than the country group (P < 0.05). Complications were managed without severe sequelae in the therapeutic hypothermia group. Conclusions: In conclusion, the noninvasive selective mild hypothermia therapy is a simple, convenient, effective way to treat patients with severe TBI. It can also improve PbtO2 gradient, reduce intracranial pressure and improve prognosis. The local brain tissue hypoxia state will be improved after mild hypothermia therapy.

Keywords:Traumatic Brain Injury, Severe, Mild Hypothermia, Partial Pressure of Brain Tissue Oxygen, Intracranial Pressure, Prognosis

亚低温治疗对重型颅脑损伤患者 PtbO2梯度的影响

陈明敏1,徐海松2,赵鹏1,裘五四2*,姜启周2

1杭州师范大学医学院,浙江 杭州

2杭州师范大学附属医院,杭州市第二人民医院,浙江 杭州

收稿日期:2017年5月4日;录用日期:2017年5月18日;发布日期:2017年5月24日

摘 要

目的:研究亚低温治疗对重型颅脑损伤患者半球脑组织氧分压(partial pressure of brain tissue oxygen, PbtO2)梯度的影响。方法:采用无创性选择性脑亚低温(头颈部降温法)治疗方法,将送至本院的60重型颅脑损伤手术后收住入病房患者随机分为亚低温组(治疗组)和常温(对照组)。亚低温治疗组采用亚低温治疗仪和降温毯继续亚低温治疗,采用头颈部降温为主,保持脑温(下述)在33℃~35℃左右,亚低温治疗维持伤后5天。对照组使用降温方法保持患者体温在正常范围内。两组患者在麻醉后行均双侧额部钻颅置入光导纤维传感器于额叶脑实质内,行两侧大脑半球脑组织氧分压梯度监护(健侧PbtO2-伤侧PbtO2),同时监测动脉血气分析、血压、脉搏、呼吸、血氧饱和度、中心静脉压和颅内压(ICP)监测。并前瞻性分析比较两组患者手术后的半球脑组织氧分压梯度、6月后的GOS评分和主要并发症(如感染、血小板减少、消化道出血、电解质紊乱等)。结果:亚低温组在治疗后24、48和72 h的大脑半球PtbO2梯度、颅内压均较对照组明显降低;亚低温组恢复良好率、病死率与常温组相比较有显著差异(P < 0.05),预后较佳(GOS评分4~5分)率明显好于常温组(P < 0.05)。未发生与亚低温治疗相关的严重并发症。结论:无创性选择性脑亚低温方法治疗重型颅脑损伤患者简单、方便、有效,具有改善PbtO2梯度,降低颅内压、改善预后的作用。亚低温治疗后可改善局部脑组织缺氧状态。

关键词 :脑外伤,亚低温,脑组织氧分压,颅内压,预后

Copyright © 2017 by authors and Hans Publishers Inc.

This work is licensed under the Creative Commons Attribution International License (CC BY).

http://creativecommons.org/licenses/by/4.0/

1. 引言

重型颅脑损伤是死亡率和致残率极高的常见神经系统损伤性疾病,尽管医学不断发展,重型颅脑损伤的治疗依然棘手。亚低温治疗对重型颅脑损伤是一种非常有前景的治疗方法 [1] [2] [3] [4] [5] 。但临床报道部分亚低温治疗效果不佳,其主要的一个主要原因未掌握好亚低温“治疗时间窗”,尤其是开始时间太迟 [1] [3] [5] [6] [7] [8] [9] 。选择性脑亚低温可减少全身亚低温治疗的并发症,并可尽早达到“脑部亚低温”的作用 [3] [5] [9] [10] [11] 。为了进一步研究亚低温脑保护作用的机理,并为临床开展相关的治疗提供参考依据,现报告如下。

2. 研究方法

2.1. 病例选择和分组

病例入选标准:1) 各种外伤原因导致的重型颅脑损伤;2) 男女不限,年龄15~69岁;3) 入院时GCS评分 ≤ 8分。同时合并其他脏器损伤所导致的严重休克及窒息等情况病例排除。

分组:将送至本院的重型颅脑损伤手术后收住入病房患者随机分为亚低温组(治疗组)和常温(对照组)。亚低温采用无创性选择性脑亚低温(头颈部降温法)治疗方法 [3] [4] [5] 。

2.2. 治疗方法和监测

主要治疗方法:患者经必要术前准备后即进行全身麻醉,开颅手术。术后收住入重症监护室,采用亚低温治疗仪和降温毯继续亚低温治疗,设定目标温度在33℃~35℃,具体方法参见文献 [5] [12] [13] [14] 。开颅术依据具体情况进行。术后使用甘露醇脱水降颅内压、鼠神经生长因子肌注神经营养等,并严密观察病情变化:治疗前后对病人的意识、瞳孔(GCS评分)、生命体征及神经系统体征、脑灌注压(CPP)等监测进行观察,定期检查血象凝血功能,血生化等 [3] [5] 。

大脑半球脑组织氧分压监测:根据术前头颅CT确定正常和损伤的脑组织区域,一般在左额发迹后2~3 cm、中线旁开2~3 cm,切开头皮3 cm,颅骨钻孔直径约5 mm,锐性穿刺硬膜,正确放置一直径0.5 mm 的光纤脑组织氧多参数监护探头于大脑皮下15~35 mm (依据损伤程度),使用英国Neurotrend脑氧代谢监护系,待监测数据稳定后开始监测(约30分钟),设定每隔15 s自动记录1次PbtO2测量值等 [5] [15] 。术后常规行头颅CT复查,监测期内均无发现监测电极端出现继发出血灶。准确显示患者脑组织氧分压(PbtO2)、颅内压(ICP)及脑温,同时监测患者神志、瞳孔、呼吸、脉搏及氧饱和度。探头放置时间1~7 d,平均5 d。

GOS评分(6月~1年):进一步分为恢复良好(GOS:4~5分)和恢复差(GOS:1~3分),并发症:死亡率、感染、血小板减少、消化道出血、电解质紊乱等。

上述研究方法家属均知情同意,且经我院伦理委员会批准。

2.3. 统计方法

使用SPSS 10.0统计软件,计量资料以± s表示,组间比较采用t 检验。两组病死率和恢复良好率的比较采用卡方检验。检验水准取α = 0.05,当P < 0.05时有统计学意义。

3. 结果

3.1. 亚低温方法的建立及脑组织氧分压监测

采用1: 1随机数字表入组60例患者,亚低温依据前述的方法进行治疗方法方便可行。亚低温组患者脑组织和直肠温度分别控制在33℃~35℃和34.5℃~36℃左右;对照组患者脑组织及直肠温度均在37℃- 38℃左右。患者进行脑组织氧分压监测,经过顺利,无出血感染等并发症发生。

3.2. 两组患者PbtO2梯度变化的比较

表1可见,亚低温组在治疗后24、48和72 h的PbtO2梯度值较对照组降低。

3.3. 两组患者颅内压变化的比较

表2可见,亚低温组在治疗后24、48和72 h的颅内压均较对照组明显降低;两组颅内压高峰均在伤后48 h出现。

3.4. 两组患者预后比较

亚低温与常温组相比较有显著差异(P < 0.05),预后较佳(GOS评分4~5分)率分别为60%和40%,明显好于常温组(P < 0.05)。

4. 讨论

近年来认为,轻度亚低温(33℃~35℃)具有治疗作用而且副作用相对较少。研究表明,亚低温治疗主要通过减轻脑缺血及继发性脑损害,控制颅内高压,改善脑灌注压来保护脑组织,并且有减轻全身炎症反应等的作用 [1] [3] [6] [7] [16] 。本研究对重型颅脑损伤患者进行的亚低温治疗,具有无创、有效的特点。降温毯内的冷水温度可根据患者的情况进行调整,以保证脑温在亚低温治疗期间控制在33℃~35℃左右。本组治疗后未见与亚低温疗法相关的严重并发症。

脑组织氧分压(Partial pressure of brain tissue oxygen, PbtO2)是指脑组织局部的氧压,氧供需平衡的一种反映。研究已证明了在脑损伤患者中,即使血压、血气均在正常范围内,仍可能出现脑组织缺血缺氧,因此准确有效地监测脑组织氧合情况,有助于早期发现和治疗脑缺血缺氧,将继发的脑缺血、缺氧性损害减少到最小,改善患者的预后 [8] [9] [10] [15] 。PbtO2监测是近年来开发出的成熟的脑组织局部氧监测技术,包括无创监测和有创监测 [17] ,而本研究使用有创监测相对于无创监测来说数值稳定准确。PbtO2正常值为25~30 mmHg,维持脑皮质功能PbtO2必须大于5 mmHg (即缺血阈值应高于5 mmHg),伤后24 h内持续PbtO2 < 5 mmHg预示患者预后不良。缺血阈值大小同时还受测定仪器技术差别、探头放置部位等多种因素的影响。

Table 1. Comparison of the dynamic changes of partial pressure of brain tissue oxygen (PbtO2) of patients (mmHg, ± SD)

表1. 两组患者PbtO2梯度(mmHg)动态变化的比较

注:与对照组比较,*P < 0.05

Table 2. Comparison of the dynamic changes of ICPs (PbtO2) of patients (mmHg, ± SD)

表2. 两组患者PbtO2梯度(mmHg)动态变化的比较

注:与对照组比较,*P < 0.05

PbtO2监测是近年来开发出的成熟的脑组织局部氧监测技术,包括无创监测和有创监测。由于无创监测PbtO2的数值会受到局部软组织温度、颅骨、颅内血流等的影响,相应的设备尚在进一步研究中。有创监测PbtO2是将微电极放置于脑组织,并且可持续监测局部脑实质氧分压和局部温度。有创监测直接监测PbtO2,可检出局灶性缺血病灶,其灵敏度达92%,特异性为84%。本研究是使用了有创PbtO2监测,具体的数据真实可靠,并显示重型颅脑损伤后脑组织不同部位PbtO2不一致,即存在“PbtO2梯度”,亚低温治疗后可降低该梯度,提示亚低温治疗的临床效果。有研究显示 [18] 亚低温治疗重型颅脑损伤过程中ICP明显下降,PbtO2逐渐升高,与常温对照组相比有显著性差异。本研究也提示亚低温治疗能降低ICP,提高PbtO2,改善PbtO2梯度。

当然,由于重型颅脑损伤的病理生理变化复杂,亚低温治疗并非适用于所有患者,部分研究还表明,亚低温治疗较常温治疗临床效果差 [1] [2] [3] [6] 。亚低温治疗作为重型颅脑损伤的二线治疗措施,其具体的效果取决于的原发性颅脑损伤和继发性颅脑损伤、正确及时的一线治疗(如开颅手术)、亚低温治疗的适应症时间窗和并发症的防治等。本研究表明,治疗性的亚低温疗法具有提高局部PbtO2、降低颅内高压和改善临床预后。PbtO2监测是一种简便、可行、有效的措施,可用于有适应症的重型颅脑损伤患者。我们进行的研究病例数相对少,而且缺乏其他如脑电监测等资料 [10] [15] 。今后的研究需要结合多参数监测颅脑损伤的临床数据,更有助于确定颅脑损伤的诊疗、进一步明确亚低温保护脑组织的具体机理。

致谢

本项目受浙江省医学会临床科研基金(2015ZYC-A36)、杭州市卫生计生委(2014A19)资助。

文章引用

陈明敏,徐海松,赵鹏,裘五四,姜启周. 亚低温治疗对重型颅脑损伤患者PtbO2梯度的影响
The Effects of Therapeutic Hypothermia on Changes in Partial Pressure of Brain Tissue Oxygen (PbtO2) Gradients for Patients with Severe Traumatic Brain Injury—Hypothermia on Partial Pressure of Brain Tissue Oxygen[J]. 亚洲急诊医学病例研究, 2017, 05(02): 15-20. http://dx.doi.org/10.12677/ACREM.2017.52004

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  19. NOTES

    *通讯作者。

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