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低温治疗重型颅脑损伤

杨树源 主任医师 天津医科大学总医院 神经外科
2009-07-02 1914人已读
杨树源 主任医师
天津医科大学总医院

 

低温治疗重型颅脑损伤的过去现状与未来

杨树源 

在上个世纪50-60年代,临床医师认为引起重型颅脑创伤(TBI)死亡的原因是脑肿胀和颅内压增高,因此认为如果能很好的控制高颅压可改善TBI的预后。Sedzimi (1) Fay(2)发现低温治疗可以降低颅内压,用其治疗颅内压增高比脱水药有效。Lund(3)在试验研究中发现低温治疗比过度换气能更有效的降低颅内压。但当时的临床医师尚不清楚最适宜的治疗温度是多少度,恰当的降温时间应该多久,如何复温及其安全性,并发症等详细情况,结果在低温治疗过程中出现严重甚至致死的并发症。上世纪90年代的实验研究发现,30℃以上短期降温能改进治疗结果,这是一个重要的发现,因为许多严重的并发症发生于低于30℃的长时间降温过程中,在上述试验基础上几个小临床试验使用亚低温(32~33℃)治疗严重TBI,发现严重并发症的发生率降低了(4)。但从近年来发表的有关低温治疗重型颅脑损伤的临床研究报告是矛盾的,在单个单位报告的前瞻性临床研究发现低温治疗有效(4,5,8,),但二个大组多中心随机对照前瞻性临床研究认为低温治疗重型TBI无效。Clifton教授牵头在美国有11个单位参加的美国国家急性颅脑损伤研究(The National Acute Brain Injury, NABIS:H)开始进行此项研究,从1994年10月至1998年5月进行,原计划完成病例500例,至1998年5月安全委员会因安全原因停止了实验继续进行。实际入组392例,低温治疗组199例,常温治疗组193例作为对照,低温组平均在8.4±3h降温至33℃,维持降温47.2±3h,结果:6月时,两组预后不良者(重残+植物状态+死亡)均为57%。低温治疗组死亡率为28%,常温组为27%(p=0.79),在年岁大于45岁,预后不良者在低温组为88%,常温组为69%,但死亡率均为38%。低温组10%产生严重低血压并发症,常温组为3%,心跳变缓,低温组为16%,常温组为4%,低温组住院天数比常温组延长。少数病人在低温治疗组出现高颅压少于常温组,他的结论是重型颅脑损伤后8小时内行33低温治疗没有改进重型颅脑损伤的预后,此临床试验研究结果刊出在著名的新英格兰医学杂志上引起了轰动,同年Shiozaki (7)在11家医院行前瞻性随机对照研究,收集病人91例,降温至34℃维持48h,3个月后预后好者在低温组占46%,常温组占59%(P>0.99)得出与Clifton相同的结论。天津医科大学总医院神经外科杨树源

对低温治疗重型TBI二种不同结果有不少评论,分析其主要原因是对低温治疗过程中影响预后的生理、代谢及用药很难在各中心完全保持一致,甚至一些大量病例在一个重症监护病房的精心监护下其结果是令人鼓舞的,在Clifton(9)多中心临床研究中确实存在各中心间的差异,如在低温治疗组平均动脉压低于70mmHg的病人比例在各中心存在差异(P<0.001)脱水(p<0.001)和脑灌注压低于50mmHg的病例比例也存在中心间差异(p<0.05),同样在各中心应用麻醉药(p<0.001)及血管加压药也存在差异(p<0.03),在其多中心研究组中有二个中心,低温治疗的结果好于其他中心(6)。

所有的临床研究报告显示低温治疗对降低颅内压增高有帮助,一些研究发现降温期有效,但降低颅内压的效果于复温后有反跳出现,因此为了防止反跳,复温过程必须要缓慢进行,应不少于12-24h。但是控制颅内压增高并不代表预后必定良好,几个临床研究报告认为低温治疗使颅内压下降并未能改变功能预后(4.6.11)。

在2007年Qiu(10)报告80例重型TBI行单侧开颅减压后行低温治疗和常温对照组相比,在伤后一年发现70%低温治疗组及48%常规治疗组有益(p<0.05)。 2007年美国第三版重型TBI救治指南在美国神经创伤杂志刊出,这是用综合再分析方法(meta-analyses)对低温治疗重型TBI临床研究的报告,共收集了354例低温治疗患者:340例常温治疗患者,此分析由6个资料完整的临床实验结果综合得出,这个分析认为低温治疗组和常温治疗组二组间在死亡率并无有意义的差别(11)。

基于以上临床研究结果,认为低温治疗不是重型颅脑损伤的标准治疗方案,但可应用它作控制顽固颅内压增高的一种手段(4)。

    

目前在国际上有多项低温治疗重型TBI的临床研究如Adelson(2005)报告75例儿童重型TBI行低温治疗的一期临床研究,并对其安全性可行性等进行Ⅲ期临床研究(Clinical Trial.gov.indentifier:NT00222742)Clifton对45岁以下成人的TBI临床研究(NABIS:HIIR;clinical  Trails .gov.identifier: NCT 00178711)澳大利亚,新西兰儿童临床研究(Clinical Trials. gov. indentifier: NCT00282269)和日本成人的临床研究(Clinical Trials. gov. indentifier: NCT00134472)(4,13). 我们期待着这些研究结果能对低温治疗重型TBI的价值作出科学的评价。

在我国每年有上百万的重型TBI患者住院治疗(12),在上世纪90年代开展低温治疗重型TBI以来我国已有近千例临床报告与基础研究报告,但各单位的方法不尽相同,观察指标、降温方法、维持时间等差异较大,难以形成强有说服力的科学指导方案,因此建议应在学会倡导下组织全国有条件的神经创伤中心,实施我国的低温治疗重型TBI的大组多中心前瞻性随机对照临床研究,总结出我国在重型TBI救治方面的经验,作出我国应有的贡献。

 

 

Paper in English

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11.  Expression on the basic fibroblast growth factor gene in mild and more severe head injury in the rats. Journal of Neurosurgery. 89: 297-362; 1998.

12.  Clinical significance of acute phase hyperglycemic in patients with severe head injury. Chinese Tramatology. 14: 36-38; 1998.

13.  Clinical results of the transoral operation for lesion of the cranio-vertebral junction and its abnormalities. Surg Neurol. 51: 16-20; 1998.

14.  Deteronination and clinical significance of plasma prostaglandin’s with acute brain injury. Surg Neurol 51: 238-245; 1999.

15.  Expression of PDGF and its receptor as well as their relationship to proliferating activity and apoptosis of menimgroinas in human meningiomas. Jounal of Clinical Neuroscience 8(suppl): 1-4; 2000.

16.  Surgical treatment of intramedullary spinal cord tumors. Abstract book 12th world of Neurosurgery. Sydney 2001.

17.  Role of caspase 3 in neuronal apoptosis after acute brain injury, Clin J Traumalotogy (English edition) 5:250~253, 2002.

18.  Therapeutic effect of nimodipine on experimental brain injury. Chinese J. of Traumatology. 2003, 6(6): 326-331.

19.  Human neural apoptosis secondary to traumatic brain injury and the regulative role of apoptosis-related genes. Chinese Journal of traumatology 2004, 7(2): 1-6.

20.  Gene therapy of rat malignant gliomas using neural stem cells expressing IL-2. DNA and cell Biology 2004;23:381-389.

21.  Comparision between proteome expression in moderate and severe traumatic brain injury in human. J Neurotrauma 23(5):782,2006.

22.  Resection of gliomas using positrion emission tomography/computered tomography neuronavigation. Neurol Med Chir(Tokyo) 2007;47:383-388.

Chapters in English:

1.      The relationship between angiographic characteristics of cerebral arteriovenous malformation and bleeding risk. in. A Hakuba(ed). Surgery of the intracramal venous system. Springer Pp525-232; 1996.

2.      Therapeutic effect of IL-1 receptor antigonist on traumatic brain edema in the rat. In wen-Ta Chiu(ed): Recent advance in Neurotraumatology. Monduzz. Pp31-36; 1999.

3.      T-tube syringoperitoneal shunt for the treatment of syringomyelia associated with Chiari I malformations. In N Tamaki. U Batzdorf and T Nagashima(eds) Syringomyelia Springer Pp 147-153; 2001.

4.      Observations on neural apoptosis and the expressions of the apoptosis-related gens secondary to human traumatic brain.   7th International Neurotrauma symposium.Meddddddimond Pp.E912c0049 14.2004.

5.      Pathogenesis of brain abscess and guidline of neurosurgical treatment. 13th World congress of neurological Surgery. Monduzz.  F619R9588. 909-913,2005.

6.      The use of neural stem cell in treating traumatic brain injury in rats. In: Stem cell Research advance. Ed.L.P Daveport,Nova Science Publisher, Inc,P203-214,2007

 

Books in Chinese:

1.          Handbook of Neurology and Neurosurgery.

2.          Atlas of Neurosurgical operation.

3.          Infection diseases of CNS.

4.          Text book of Neurosurgery. People’s Medical Publishing House.

Chapters in Chinese:

 

1.      Cranum tumors in: Wu Jie-ping, Qiu Fa-zu eds. Text book of surgery. People’s Medical Publisher House. 2000 Beijing 6 edit. Pp 658-659.

2.      Intracranial meningiomas        as above.

3.      Acoustic neuroma              as above.

4.      intraspinal tumours             as above.

5.      Brain abscess.  In: Shi Y. Q. (Ed) Chinese Medical encyclopedia. Neurosurgery Volume. Shanghai science and technique. Publisher house, 1982, P 48-51.

6.      Arteriovenous malformation of spinal cord.   as above

7.       Aneurysm of spinal cord     as above

8.      Intracranial tumors In: Yang L. C, ed. Clinical Neurology Tijain People’s Publisher house. 1977 2 edition.

9.      Brain injury. In Yang L.C. ed. Clinical Neurology. Tianjin People’s publisher house. 1971, 1st edition.

10.  Compression of spinal cord disease. In Chou S.Y. ed. Textbook of Medicine. Tianjin sciences and technique publisher house. 1982, Vol 5.

11.  Operative planning of brain injury In: Jong J.E. and Chou C. (eds). The gridline of craniocerebral injury. The 2nd Military Medical University Press 2002, Pp 27-38.

Paper in Chinese:

1.      The inhibitory effect of PDGF B chain antisene oligonucleotides on the growth of meningioma cells in vivo. Chin J Neurosurg 19: 103~105, 2003.

2.      The experimental study on expression and activation of caspase 3 in neuron after brain trauma. Chin J Neurosurg. 18: 375~378, 2002.

3.      Neurol stem cells transplantation after traumatic brain injury improving functional outcome in adult rats. Chin J Neurosurg. 18: 282~285, 2002.

4.      The inhibitory effect of PDGF B Chain antisense oligonucleotides on the growth of meningioma cell in vitro. Chinese Journal of Nervous and Mental disease 28: 107-119; 2002.

5.      Difference in proliferation between invasive and noninvasive prolactinomas. Chinese Journal of Nervous and Mental disease 28: 113-114; 2002.

6.      Long-term follow-up of microsurgical treatment of intramedullary spinal cord tumors. Chinese Journal of Neurosurgical Research. 1: 18-21; 2002.

7.      Neuron stem cell and its application in the future. Clinical Medicine of Neurosurgeruy 4: 1-3; 2002.

8.      Mismatch repair gene and brain tumors. Chinese Journals of clinical Neurosciences 9: 320-322; 2001.

9.      The experimental observation of therapy effect of b FGF on delayed neuron death after brain trauma. Chinese Journal of Experimental Surgery 18: 150; 2001.

10.  Neuro-stem cell. Modern Journal of Neurology and Neurosurgery. 1: 9-10; 2001.

11.  Study on therapeutic effect of nimodipine in experimental brain injury. Modern Journal of Neurology and Neurosurgery. 1: 42-47; 2001.

12.  Promote neuro-stem cell research work. Chinese Journal of Neurosurgery. 17: 235-238; 2001.

13.  Expression of PDGF and its receptors in human meningomas as well as its relationship of proliferating activity and apoptosis of meningiomas. Chinese Journal of Neurosurgery 17: 17-20; 2001.

14.  Study on the effect of EGF on stem cell from embryonic rat’s striatum. Chinese Journal of Neurosurgery. 17: 239-242; 2001.

15.  Study on the biological properties of cells from embryonic rat hoippocampi. Chinese Journal of Nervous and Mental diseases. 27: 273-275; 2001.

16.  The correlation between ER gene expression in prolactin adenomas and it proliferative ability. Chinese Journal of Clinical Neurosurgery 6: 90-92; 2001.

17.  Expression of PDGF and its receptors as well as their relationship to proliferating activity and apoptosis of memngiomas Chinese Journal of Neursurgery. 17: 17-20; 2001.

18.  Intracranial infections in neurosurgery. Chinese Journal of Neurosurgery (Suppl) 16: 52-57; 2000.

19.  Intraspinal tumors of 402 cases. Chinese Journal of Neurosurgery. 16: 162-164; 2000.

20.  The research of acute protein expression after severe traumatic brain with proteome techni . Chin J Neurosurg. 21:363-366, 2005.

21.   The research of the differential human cortex proteome after primary mechanical traumatic brain injury. Chin J. Neurosurg  Chin J Neurosurg 22:72-75,2006

 

 

 

 

 

 

 

 

 

 

 

 

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作者单位:

杨树源 (天津医科大学总医院神经外科

 

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杨树源 主任医师

天津医科大学总医院 神经外科

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