在创伤性脑损伤的预防性治疗管理
Jennifer Confer, PharmD 詹妮弗康弗，药学博士
Critical Care Clinical Specialist 危重病急救临床专家
Cabell Huntington Hospital 卡贝尔亨廷顿医院
Clinical Assistant Professor 临床助理教授
West Virginia University School of Pharmacy 西弗吉尼亚大学药学院
Huntington, West Virginia 亨廷顿，西弗吉尼亚州
Jon Wietholter, PharmD 乔恩Wietholter，药学博士
Internal Medicine Clinical Specialist 内科临床专科
Cabell Huntington Hospital 卡贝尔亨廷顿医院
Clinical Assistant Professor 临床助理教授
West Virginia University School of Pharmacy 西弗吉尼亚大学药学院
Huntington, West Virginia 亨廷顿，西弗吉尼亚州
11/19/2009 2009年11月19日
US Pharm . 美国医药 。 2009;34(11):HS10-HS19. 2009年，34（11）：HS10 - HS19。
Traumatic brain injury (TBI), defined as a strong impact to the head or a penetrating head injury that alters the function of the brain, affects the lives of approximately 1.4 million people in the United States each year. 1 TBI currently accounts for an estimated 1.1 million emergency department admissions and 50,000 deaths annually.外伤性脑损伤（TBI），脑定义为一个强烈冲击的头部或穿透头部受伤，改变了的功能，影响一头部创伤患者的生命，约140万人口，每年在美国。目前估计占110万急诊的人数，每年50,000人死亡。 Individuals at highest risk for TBI are young children 6 months to 4 years old, males between the ages of 15 and 30 years, elderly individuals (aged 75 years or older), and certain military personnel.在个人的创伤性脑损伤的风险最高的青少年儿童6个月至4岁之间，15岁至30岁，（年龄在75岁或以上）的老年人的男性，和某些军事人员。 According to the CDC, the leading causes of TBI include falls (28%), motor vehicle crashes (20%), events in which a person is struck by or against an object (19%), and assaults (11%). 1根据课程发展议会，原因主要包括：跌倒头部外伤（28％），机动车辆事故（20％），）的事件，其中一人是深刻的，或对一个对象（19％），和攻击（11％。1
Types of Injuries伤害类型
To appropriately treat and provide care to patients with TBI, it is important to understand the mechanism and pathophysiology behind the injury.为了提供适当的治疗和护理，与颅脑创伤患者，重要的是要了解背后的损伤机制和病理生理学。 There are three key mechanisms of injury—blunt, penetrating, and blast, which are further divided into primary or secondary injuries. 2 Blunt injuries are the most common cause of TBI and are frequently the result of motor vehicle (ie, automobile, motorcycle, pedestrian) crashes, falls, sports-related injuries, and assaults.有三个关键机制的伤害钝，尖锐的，baozha，这是更多的伤害分为小学或中学的伤害。2布朗特是导致创伤性脑损伤最常见，结果往往是汽车的车辆（即汽车，摩托车，行人）崩溃，跌倒，运动有关的伤害和殴打。 Penetrating injuries result when any sharp or blunt object penetrates the scalp or skull (eg, gunshot wounds).穿透性受伤而当任何尖锐或钝物穿透头皮或颅骨（如枪伤）。 Lastly, blast wounds are the result of a combination of blunt and penetrating injuries.最后，baozha伤是一个直率和穿通伤结合的结果。
In addition to identifying the mechanism of injury, TBI is also separated into either primary or secondary injury. 2 A primary injury occurs at the time of injury and directly damages neuronal tissue.除了确定的损伤机制的研究，脑外伤，也分为原发或继发性损伤。2伤发生在一个主要的时间和直接损伤神经组织的损害。 Resultant lesions from a primary injury are either focal, where the injury is in a localized area of the brain, or diffuse, in which the injury is large and widespread.从主损伤病变的结果不是重点，其中损伤的大脑，或弥漫性，在这种损害是巨大而广泛的本地化面积。 The secondary injury that occurs from TBI is not initially seen; instead it is the result of a normal physiological response to the primary injury, such as tissue hypoxia, that develops over a period of time from hours to months following the primary injury. 2颅脑创伤的继发性损伤的发生并非由最初出现，反而是缺氧的结果是正常的生理反应的主要组织损伤，如超过1小时，开发周期从几个月的时间后，主要伤害。2
For decades, the concentration of TBI management was on maintaining the control of intracranial pressure (ICP) and cerebral perfusion pressure.几十年来，脑外伤管理的浓度保持颅内压（ICP控制）和脑灌注压。 As will be discussed, the focus of TBI management no longer resides in one central area; instead, managing all aspects of TBI are now important areas of therapeutic decision making.正如将要讨论的，脑外伤管理的重点不再驻留在一个中心区域，而是管理的各个方面，是脑外伤的治疗决策现在重要的领域。 Building upon the 2007 Guidelines for the Management of Severe Traumatic Brain Injury, this article will focus on prophylactic therapies currently being used and recommended in patients with TBI ( TABLE 1 ).重型颅脑损伤的建设后，2007年准则的管理，本文将重点放在预防和治疗目前正在使用的）建议1例脑外伤（ 表 。
Prophylactic Steroids预防类固醇
Beneficial effects of corticosteroids in TBI were originally discovered in the 1960s.在创伤性脑损伤皮质类固醇的有益影响，原本在20世纪60年代发现的。 At that time, corticosteroids were thought to be favorable through a significant reduction in brain edema, a decrease of cerebrospinal fluid production, and the lessening of free radical production.当时，类固醇被认为是有利的，通过在脑水肿，脑脊髓液的生产下降，自由基的生产减少显着减少。 Since then, there have been numerous clinical studies examining the role that corticosteroids play in neurological procedures, as well as in TBI.自那时以来，已有众多研究糖皮质激素发挥作用，在神经系统的程序，以及在颅脑创伤的临床研究。 In 1976, two trials were conducted comparing low- and high-dose glucocorticoids in patients with severe TBI. 3,4 Results of these trials demonstrated favorable response to high-dose glucocorticoid groups and favorable dose-related effects on mortality. 1976年，两次审判进行比较大剂量糖皮质激素在脑外伤患者有严重的低和。3,4试验结果表明，这些有利的反应大剂量糖皮质激素组和良好的剂量效应相关的死亡率。 Successively, in the 1980s and 1990s, there were further trials that evaluated clinical outcomes in patients with TBI, ICP, or both.先后在20世纪80年代和90年代，也有评价，与脑外伤，颅内压，或两名患者的临床结果进一步试验。 None of the studies demonstrated a sizeable benefit in using glucocorticoids in those patients. 5没有任何研究的病人表现出相当大的糖皮质激素的使用效益。5
More recently, in 2004, the CRASH (Corticosteroid Randomization After Significant Head Injury) trial authors described the results of an international randomized, controlled trial in patients with TBI using high-dose methylprednisolone (2-g IV methylprednisolone followed by 0.4 mg/h for 48 h) or placebo. 6 The study was concluded early due to an interim analysis that demonstrated a harmful effect of methylprednisolone, particularly with regard to mortality.最近，在2004年，崩溃（类固醇严重头部损伤后，随机）试验作者描述了一个国际随机，脑外伤患者与对照试验结果使用大剂量甲基强的松龙（2克四甲基强的松龙0.4毫克/小时随访48 h）或安慰剂。6研究得出结论，由于早期的中期分析，表明，关于特别是死亡率甲泼尼龙有害影响。 The authors thus concluded that although the cause of increase in mortality was unclear, the detrimental effects were not different among groups of patients further classified by injury severity.作者们就此得出结论，虽然死亡率增加的原因还不清楚，没有的不利影响中进一步损伤程度分为不同的病人群体。
In general, the use of prophylactic corticosteroids is not recommended at this time for improving patient outcomes or reducing ICP/edema in patients with TBI. 5 Furthermore, it is concluded that high-dose methylprednisolone may be correlated with an increase in mortality.在一般情况下，皮质类固醇使用预防性目前并不建议这个时候脑外伤患者的治疗效果或改善患者减少水肿备案号/。5此外，可以得出结论，高剂量的甲基强的松龙可与死亡率增加相关。 Due to the results of recent trials, there is little interest in pursuing further research in this area at this time.由于最近的试验的结果，是在追求这方面的进一步研究在这个时候兴趣不大。
Infection Prophylaxis感染的预防
With an increased incidence of mechanical ventilation and other invasive aspects of patient monitoring and treatment, patients with TBI are at a significantly increased likelihood of developing infections.与1的机械通风和病人监护和治疗等侵入性方面的发病率升高，与脑外伤病人正处于发展中的感染显着增加的可能性。 The issue of infection prophylaxis has been evaluated by numerous sources and has revolved around different possibilities of infection development.感染的预防问题进行了评估，并已通过多种渠道围绕旋转感染不同发展的可能性。
One possible infection source is through the insertion of ICP devices.一个可能的感染源是通过对ICP设备插入。 The incidence of ICP device infection can range from less than 1% to 27%. 7 Even with these striking infection rates, there are conflicting data concerning what the appropriate prophylactic measures should contain for patients with TBI.感染的发生率比较方案的设备可以从不到1％至27％。感染率7即使这些引人注目的，有冲突的数据与头部外伤有关什么适当的预防措施应包含病人。 Most studies cited by the 2007 guidelines evaluating prophylactic antibiotic usage in patients with external ventricular drainage have shown no difference in infection rates.大多数研究引用2007年评估预防与室外引流病人抗生素使用指南，没有表现出在感染率差异。 Additionally, one study showed that patients receiving bacitracin flushes experienced a significantly higher infection rate than those without prophylactic measures. 7此外，一项研究表明，患者接受杆菌肽刷新经历了那些没有预防措施，显着高于高感染率。 七
Prophylactic antibiotic use in patients with TBI have shown no meaningful reduction in nosocomial infections. 7 In addition, an increase in serious gram-negative infections was noted in this population.与颅脑创伤患者预防性使用抗生素在院内感染没有表现出有意义的减少英寸另外7在，增加了感染的严重革兰阴性是人口注意到这一点。 The guidelines also cite data showing an increase in resistant or gram-negative nosocomial pneumonias.该准则还举出数据显示，在抗或革兰氏阴性院内肺炎增加。 This was seen when prophylactic antibiotics were given for longer than 48 hours in general trauma patients.这被看作是作预防性抗生素时不超过48小时，一般外伤患者给予。 In contrast, one study showed a decrease in pneumonias when prophylactic antibiotics were given to patients with TBI.相反，一项研究显示，减少肺炎时给予预防性抗生素与脑外伤病人。 No difference in mortality was noted, so it is difficult to assess the usefulness of this therapeutic avenue. 7没有死亡率的差异在会上指出，因此很难评估这种治疗有效性的途径。 七
Since publication of the 2007 guidelines, one further study in patients with TBI has been completed. 8 This study retrospectively evaluated the use of antibiotic prophylaxis in patients with ICP monitor implantation.自2007年出版的准则，其中一人头部外伤病人的进一步研究工作已经完成。8本研究回顾性评价了植入颅内压监测与使用抗生素预防患者。 Of the 155 patients included in the analysis, only two developed CNS infections, and these were both in the group that received prophylactic antibiotics.对155例患者的分析中，只有两个发达国家中枢神经系统感染，而这些都在预防性抗生素组收到了。 Additionally, both complications from infections and multidrug resistant infections were significantly increased in the group that received antibiotics.此外，无论从感染并发症及耐药性感染显着增加了组收到的抗生素。
In summary, there are currently no convincing data to support infection prophylaxis in patients with TBI, especially in light of data suggesting that prophylaxis might predispose patients to more severe infections when infections would arise. 7,8 To be fair, there is a relative lack of data to give any definitive statement on the use of prophylactic antibiotics, but at this time this practice cannot be supported.总之，目前没有任何令人信服的数据，以支持在预防脑外伤感染患者，尤其是在光线会出现的数据表明预防有可能使患者容易感染时更严重的感染。7,8公平地说，有一个相对缺乏数据提供任何有关预防性使用抗生素的明确声明，但在这种做法是不能支持的时间。
Venous Thromboembolism Prophylaxis静脉血栓栓塞症的预防
Venous thromboembolism (VTE) is a topic that is very pertinent to patients with TBI, as they are at an increased risk of developing blood clots due to their typically persistent immobile state.静脉血栓（VTE）是一个主题，这是非常中肯与头部外伤病人，因为他们在发展中的一个血块，因为它们通常不动的状态持续上升的风险。 The development of deep vein thrombosis (DVT) in patients with TBI who do not receive prophylaxis is as high as 25%. 9 However, there remains some uncertainty about the appropriateness of VTE prophylaxis due to the questionable safety of anticoagulation in patients who have TBI.颅脑创伤发展的深部静脉血栓形成（DVT）与病人谁不接受预防是高达25％。9然而，仍然存在一些不确定性谁是合适的患者抗凝预防静脉血栓栓塞的安全性问题因脑外伤。 Mechanical means of VTE prophylaxis such as sequential compression devices seem to carry less risk in patients with TBI, but concomitant lower limb injuries can prevent their use in some patients.机械职业教育预防手段，如连续进行压缩设备似乎少与颅脑创伤患者的风险，但随之而来的下肢伤害可以防止他们在某些病人使用。 Per the 2007 guidelines, mechanical VTE prophylaxis is recommended in all severe patients with TBI who have no contraindications to usage, such as an intracranial bleed. 10 2007年每准则，机械静脉血栓栓塞预防建议到使用，所有重型颅脑创伤患者谁没有禁忌症，如颅内出血。10
Concerning pharmacologic options, the guidelines suggest that low-molecular-weight heparin (LMWH) or low-dose unfractionated heparin (UFH) should be used in addition to mechanical means of VTE prophylaxis when no contraindications to LMWH or UFH exist.关于药理选项，指引表明，低分子量肝素（LMWH）或低剂量普通肝素（UFH的）应该是除机械职业教育预防手段时没有低分子肝素或普通肝素的禁忌存在。 It is important to note, however, that the guidelines do not elicit a preferred agent, dosage, or timing of pharmacologic prophylaxis and also warn of the increased risk of intracranial hemorrhage expansion. 10重要的是要注意，但是，这些准则并没有引起首选剂，剂量，或预防措施的时机也警告的药理和扩张的出血风险增加颅内。10
Three studies have been published since the guidelines on pharmacologic VTE prophylaxis in patients with TBI. 11-13 A 2007 prospective study evaluated the use of dalteparin in trauma patients in which 23% were patients with TBI. 11 These patients received prophylactic dalteparin (5,000 units SQ once daily) if there was no active or progressing bleed on CT scan. 3项研究已发表与脑外伤后患者的预防指引，职业教育在药理。11-13 2007年的前瞻性研究评估了颅脑创伤使用阿昔洛韦创伤患者，其中23％的的病人。11这些患者接受预防性阿昔洛韦（5,000个单位智商每日一次），如果没有积极的进展或出血的CT扫描。 No patients developed or had increased intracranial bleeding after initiation of dalteparin, while only 3.9% of patients had evidence of DVT and 0.8% had evidence of pulmonary embolism.无1例是发达国家还是增加了启动后，阿昔洛韦颅内出血，而只有3.9％的患者深静脉血栓形成的证据和0.8％的人肺动脉栓塞的证据。 A second prospective study published in 2008 evaluated the use of enoxaparin (30 mg SQ twice daily) in patients with TBI. 12 Progressive hemorrhagic injury was seen in 3.4% of the TBI population, with 67% of those patients having clinically insignificant hemorrhagic changes.第二项前瞻性研究中评估了2008年出版使用依诺肝素（30毫克，每日两次平方脑外伤）的患者。12进出血损伤主要出现在3.4％的人口变化的脑外伤，失血性微不足道的67％的病人有临床。 In addition, one patient died from a potential side effect from enoxaparin usage.此外，1例死于由依诺肝素的使用潜在的副作用。 The authors of these two studies concluded that enoxaparin and dalteparin are safe options in patients with TBI and that both agents have a relatively low risk of significant bleeding complications. 11,12在这些研究的结论提交两个与依诺肝素和阿昔洛韦颅脑创伤患者选择安全，而且在这两种药物有显着的出血并发症的风险相对较低。11,12
A retrospective study published in 2009 looked at a comparison of the risk of DVT in patients with and without TBI utilizing either LMWH or UFH (doses not specified). 13 This study showed a three- to fourfold increase in DVTs in patients with TBI using relative risks with 95% confidence intervals.回顾分析2009年出版的看着一个比较深静脉血栓患者的风险和不使用任何头部外伤低分子肝素或普通肝素（指定剂量不）。13本研究显示三至四倍TBI的增加与患者在使用相对DVTs风险，95％的置信区间。 The highest rate was noted when prophylaxis was started greater than 48 hours after insult.发病率最高的是预防时指出大于48小时后开始的侮辱。
In summary, it is currently acceptable to recommend mechanical and pharmacologic VTE prophylaxis in patients with TBI that have no contraindications to usage. 10-13 The evidence is shifting in favor of quick initiation of prophylactic agents regardless of product selection.总之，它目前正在接受推荐使用上没有任何禁忌和药理学机制上预防静脉血栓栓塞患者头部外伤。10-13证据是代理人在开展预防性转移迅速失宠不管产品的选择。 However, the breakpoint for deciding between mechanical and pharmacologic choices or agents is still unknown and should be a course of future study.但是，机械和药理学之间的选择或代理人仍是未知的，应是今后的研究方向决定断点。
Seizure Prophylaxis海关检获预防
Posttraumatic seizure (PTS) is a common occurrence in patients with TBI.外伤性癫痫（PTS）为一个与颅脑创伤患者屡见不鲜。 These seizures are broken into two groups: early (within 7 days of injury) and late (after 7 days).这些缉获分为两组：早期（伤后7天）和晚期（后7天）。 Certain risk factors have been shown to place patients with TBI at increased risk for PTS.某些风险因素已被证明在地方与脑外伤患者的PTS风险增加。 These risk factors include: Glasgow Coma Score (a neurological scale used to assess level of consciousness) less than 10; cortical contusion; depressed skull fracture; subdural, intracerebral, and epidural hematoma; penetrating head wound; or seizure within 24 hours after injury. 14这些风险因素包括：格拉斯哥昏迷评分（1神经规模用于评估小于10;皮质挫伤;凹陷性颅骨骨折，硬膜下，脑内血肿，硬膜外;穿透头部受伤，或在24小时内发作的意识水平）伤后。 14
Phenytoin and valproate sodium have been studied in the prevention of early and late PTS.苯妥英钠和丙戊酸钠进行了研究在早期和晚期警校预防。 One study cited by the 2007 guidelines showed a significant reduction in early PTS without showing any significant effect on late PTS or survival with the use of phenytoin. 14 In contrast, a randomized, double-blind study showed no early or late PTS benefit by using phenytoin.引述一项研究显示，由2007年的指导方针生存与使用苯妥英的重大晚在警校或减少早期警校没有显示任何重大影响。14相反，随机，双盲研究显示，没有早或晚使用警校受益苯妥英。 Valproate sodium has shown a similar rate of early PTS reduction when compared to phenytoin.丙戊酸钠已经表现出了类似的早期警校率降低相比，苯妥英。 However, a trend toward higher mortality in the valproate sodium group was noted and could be cause for concern. 14然而，一组高死亡率的趋势对钠丙戊酸钠在会上指出，可担心的。 十四
Since the publication of the guidelines, there have been two pertinent studies completed regarding seizure prophylaxis. 15-16 The first, a study from 2008, compared the incidence of seizures in patients with TBI when randomized to either phenytoin or levetiracetam. 15 Results indicated that there was no significant difference in seizure incidence.由于出版的指引，有两个相关的研究，完成了关于预防发作。15-16第一，从2008年的一项研究，比较了颅脑创伤的发生率与患者在发作时，随机分为苯妥英或左乙拉西坦。结果表明，15有没有发作的发生率显着差异。 However, patients receiving levetiracetam showed increased incidence of electroencephalogram (EEG) abnormalities.然而，左乙拉西坦显示患者接受脑电图发生率增加（脑电图）异常。 An EEG was indicated if patients displayed persistent coma, decreased mental status, or clinical signs of seizures.与会者指出，如果一个患者脑电图显示持续昏迷，精神状况，或发作的症状。
The second study evaluated the incidence of late PTS in patients with TBI who did or did not receive antiseizure prophylaxis upon initial presentation. 16 This study was carried out in Italy, with phenobarbital being one of the main agents used in antiseizure prophylaxis.第二项研究评估了颅脑创伤患者的发病率与警校下旬谁没有或没有接受抗抽搐预防本研究在初步报告。16在意大利进行，与苯巴比妥预防1被用于抗癫痫药物的主要。 Interestingly, in the retrospective portion of the study, 29% of patients who received antiseizure prophylaxis developed late PTS, while only 13% of patients who did not receive prophylaxis developed late PTS.有趣的是，在这项研究中，29例接受抗抽搐预防谁开发后期警校，％追溯部分，而只有13％的患者未接受谁开发后期警校预防。 While the retrospective data were not statistically significant, the prospective data were even more striking.虽然追溯的数据在统计学上没有显着，未来的数据更是惊人的。 A significant difference was noted in the prospective group, where 39% of patients treated with antiseizure prophylaxis developed late PTS, while none of the patients who were not treated with antiseizure prophylaxis developed late PTS.一个显着性差异注意到准组，其中以抗39％的患者制定预防治疗晚期警校，而没有对谁不发达国家与抗癫痫预防治疗晚期警校的病人。 However, phenobarbital is not commonly used in the US in this regard because of its adverse-effect profile and multiple drug interactions, and because more appropriate antiepileptic selections are available; therefore, results must not be generalized too drastically.然而，苯巴比妥不常用在美国这是因为其不利效应形象和多种药物的相互作用方面，由于更多的选择，可适当抗癫痫药物，因此，结果不能概括得太过分。
In summary, current literature including the 2007 guidelines indicates that the incidence of early PTS appears to be reduced with the addition of prophylactic antiseizure medications. 14 However, there is currently no evidence to indicate that prophylactic antiseizure medications alter mortality or incidence of late PTS, and it is still unknown whether or not this course of therapeutic prophylaxis is currently benefitting patients.总之，目前的文献，包括2007年的指导方针表明，警校发病早期似乎与抗癫痫药物降低预防性的加法。14然而，目前还没有证据表明，预防性抗癫痫药物改变警察训练学校发生死亡或晚，它目前仍是未知之患者是否受益这不是治疗预防课程。
Conclusion结论
Traumatic brain injury can be overwhelming and distressing to both patients and their family members.外伤性脑损伤可以变得十分艰巨和痛苦的病人和他们的家属。 In addition to the emotional and social impacts that accompany TBI, it is important to identify and deliver prompt attention to the physical needs of the patient.除了情绪和社会影响，伴随头部外伤，重要的是要确定和提供及时注意病人的身体的需要。 Prophylactic medications play an important role in patients with TBI, yet as of now many categories lack definitive data to direct appropriate therapeutic choices.预防性药物在发挥脑外伤患者的重要作用，但由于目前缺乏明确的数据，许多类别直接适当的治疗选择。 Future studies are needed to clarify this important issue in the management of patients with this condition.未来的研究需要澄清的病人管理这个条件这一重要问题。
REFERENCES考
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To comment on this article, contact [email protected].评论这篇文章，请联系[email protected]。
在创伤性脑损伤的预防性治疗管理
Jennifer Confer, PharmD 詹妮弗康弗，药学博士
Critical Care Clinical Specialist 危重病急救临床专家
Cabell Huntington Hospital 卡贝尔亨廷顿医院
Clinical Assistant Professor 临床助理教授
West Virginia University School of Pharmacy 西弗吉尼亚大学药学院
Huntington, West Virginia 亨廷顿，西弗吉尼亚州
Jon Wietholter, PharmD 乔恩Wietholter，药学博士
Internal Medicine Clinical Specialist 内科临床专科
Cabell Huntington Hospital 卡贝尔亨廷顿医院
Clinical Assistant Professor 临床助理教授
West Virginia University School of Pharmacy 西弗吉尼亚大学药学院
Huntington, West Virginia 亨廷顿，西弗吉尼亚州
11/19/2009 2009年11月19日
US Pharm . 美国医药 。 2009;34(11):HS10-HS19. 2009年，34（11）：HS10 - HS19。
Traumatic brain injury (TBI), defined as a strong impact to the head or a penetrating head injury that alters the function of the brain, affects the lives of approximately 1.4 million people in the United States each year. 1 TBI currently accounts for an estimated 1.1 million emergency department admissions and 50,000 deaths annually.外伤性脑损伤（TBI），脑定义为一个强烈冲击的头部或穿透头部受伤，改变了的功能，影响一头部创伤患者的生命，约140万人口，每年在美国。目前估计占110万急诊的人数，每年50,000人死亡。 Individuals at highest risk for TBI are young children 6 months to 4 years old, males between the ages of 15 and 30 years, elderly individuals (aged 75 years or older), and certain military personnel.在个人的创伤性脑损伤的风险最高的青少年儿童6个月至4岁之间，15岁至30岁，（年龄在75岁或以上）的老年人的男性，和某些军事人员。 According to the CDC, the leading causes of TBI include falls (28%), motor vehicle crashes (20%), events in which a person is struck by or against an object (19%), and assaults (11%). 1根据课程发展议会，原因主要包括：跌倒头部外伤（28％），机动车辆事故（20％），）的事件，其中一人是深刻的，或对一个对象（19％），和攻击（11％。1
Types of Injuries伤害类型
To appropriately treat and provide care to patients with TBI, it is important to understand the mechanism and pathophysiology behind the injury.为了提供适当的治疗和护理，与颅脑创伤患者，重要的是要了解背后的损伤机制和病理生理学。 There are three key mechanisms of injury—blunt, penetrating, and blast, which are further divided into primary or secondary injuries. 2 Blunt injuries are the most common cause of TBI and are frequently the result of motor vehicle (ie, automobile, motorcycle, pedestrian) crashes, falls, sports-related injuries, and assaults.有三个关键机制的伤害钝，尖锐的，baozha，这是更多的伤害分为小学或中学的伤害。2布朗特是导致创伤性脑损伤最常见，结果往往是汽车的车辆（即汽车，摩托车，行人）崩溃，跌倒，运动有关的伤害和殴打。 Penetrating injuries result when any sharp or blunt object penetrates the scalp or skull (eg, gunshot wounds).穿透性受伤而当任何尖锐或钝物穿透头皮或颅骨（如枪伤）。 Lastly, blast wounds are the result of a combination of blunt and penetrating injuries.最后，baozha伤是一个直率和穿通伤结合的结果。
In addition to identifying the mechanism of injury, TBI is also separated into either primary or secondary injury. 2 A primary injury occurs at the time of injury and directly damages neuronal tissue.除了确定的损伤机制的研究，脑外伤，也分为原发或继发性损伤。2伤发生在一个主要的时间和直接损伤神经组织的损害。 Resultant lesions from a primary injury are either focal, where the injury is in a localized area of the brain, or diffuse, in which the injury is large and widespread.从主损伤病变的结果不是重点，其中损伤的大脑，或弥漫性，在这种损害是巨大而广泛的本地化面积。 The secondary injury that occurs from TBI is not initially seen; instead it is the result of a normal physiological response to the primary injury, such as tissue hypoxia, that develops over a period of time from hours to months following the primary injury. 2颅脑创伤的继发性损伤的发生并非由最初出现，反而是缺氧的结果是正常的生理反应的主要组织损伤，如超过1小时，开发周期从几个月的时间后，主要伤害。2
For decades, the concentration of TBI management was on maintaining the control of intracranial pressure (ICP) and cerebral perfusion pressure.几十年来，脑外伤管理的浓度保持颅内压（ICP控制）和脑灌注压。 As will be discussed, the focus of TBI management no longer resides in one central area; instead, managing all aspects of TBI are now important areas of therapeutic decision making.正如将要讨论的，脑外伤管理的重点不再驻留在一个中心区域，而是管理的各个方面，是脑外伤的治疗决策现在重要的领域。 Building upon the 2007 Guidelines for the Management of Severe Traumatic Brain Injury, this article will focus on prophylactic therapies currently being used and recommended in patients with TBI ( TABLE 1 ).重型颅脑损伤的建设后，2007年准则的管理，本文将重点放在预防和治疗目前正在使用的）建议1例脑外伤（ 表 。
Prophylactic Steroids预防类固醇
Beneficial effects of corticosteroids in TBI were originally discovered in the 1960s.在创伤性脑损伤皮质类固醇的有益影响，原本在20世纪60年代发现的。 At that time, corticosteroids were thought to be favorable through a significant reduction in brain edema, a decrease of cerebrospinal fluid production, and the lessening of free radical production.当时，类固醇被认为是有利的，通过在脑水肿，脑脊髓液的生产下降，自由基的生产减少显着减少。 Since then, there have been numerous clinical studies examining the role that corticosteroids play in neurological procedures, as well as in TBI.自那时以来，已有众多研究糖皮质激素发挥作用，在神经系统的程序，以及在颅脑创伤的临床研究。 In 1976, two trials were conducted comparing low- and high-dose glucocorticoids in patients with severe TBI. 3,4 Results of these trials demonstrated favorable response to high-dose glucocorticoid groups and favorable dose-related effects on mortality. 1976年，两次审判进行比较大剂量糖皮质激素在脑外伤患者有严重的低和。3,4试验结果表明，这些有利的反应大剂量糖皮质激素组和良好的剂量效应相关的死亡率。 Successively, in the 1980s and 1990s, there were further trials that evaluated clinical outcomes in patients with TBI, ICP, or both.先后在20世纪80年代和90年代，也有评价，与脑外伤，颅内压，或两名患者的临床结果进一步试验。 None of the studies demonstrated a sizeable benefit in using glucocorticoids in those patients. 5没有任何研究的病人表现出相当大的糖皮质激素的使用效益。5
More recently, in 2004, the CRASH (Corticosteroid Randomization After Significant Head Injury) trial authors described the results of an international randomized, controlled trial in patients with TBI using high-dose methylprednisolone (2-g IV methylprednisolone followed by 0.4 mg/h for 48 h) or placebo. 6 The study was concluded early due to an interim analysis that demonstrated a harmful effect of methylprednisolone, particularly with regard to mortality.最近，在2004年，崩溃（类固醇严重头部损伤后，随机）试验作者描述了一个国际随机，脑外伤患者与对照试验结果使用大剂量甲基强的松龙（2克四甲基强的松龙0.4毫克/小时随访48 h）或安慰剂。6研究得出结论，由于早期的中期分析，表明，关于特别是死亡率甲泼尼龙有害影响。 The authors thus concluded that although the cause of increase in mortality was unclear, the detrimental effects were not different among groups of patients further classified by injury severity.作者们就此得出结论，虽然死亡率增加的原因还不清楚，没有的不利影响中进一步损伤程度分为不同的病人群体。
In general, the use of prophylactic corticosteroids is not recommended at this time for improving patient outcomes or reducing ICP/edema in patients with TBI. 5 Furthermore, it is concluded that high-dose methylprednisolone may be correlated with an increase in mortality.在一般情况下，皮质类固醇使用预防性目前并不建议这个时候脑外伤患者的治疗效果或改善患者减少水肿备案号/。5此外，可以得出结论，高剂量的甲基强的松龙可与死亡率增加相关。 Due to the results of recent trials, there is little interest in pursuing further research in this area at this time.由于最近的试验的结果，是在追求这方面的进一步研究在这个时候兴趣不大。
Infection Prophylaxis感染的预防
With an increased incidence of mechanical ventilation and other invasive aspects of patient monitoring and treatment, patients with TBI are at a significantly increased likelihood of developing infections.与1的机械通风和病人监护和治疗等侵入性方面的发病率升高，与脑外伤病人正处于发展中的感染显着增加的可能性。 The issue of infection prophylaxis has been evaluated by numerous sources and has revolved around different possibilities of infection development.感染的预防问题进行了评估，并已通过多种渠道围绕旋转感染不同发展的可能性。
One possible infection source is through the insertion of ICP devices.一个可能的感染源是通过对ICP设备插入。 The incidence of ICP device infection can range from less than 1% to 27%. 7 Even with these striking infection rates, there are conflicting data concerning what the appropriate prophylactic measures should contain for patients with TBI.感染的发生率比较方案的设备可以从不到1％至27％。感染率7即使这些引人注目的，有冲突的数据与头部外伤有关什么适当的预防措施应包含病人。 Most studies cited by the 2007 guidelines evaluating prophylactic antibiotic usage in patients with external ventricular drainage have shown no difference in infection rates.大多数研究引用2007年评估预防与室外引流病人抗生素使用指南，没有表现出在感染率差异。 Additionally, one study showed that patients receiving bacitracin flushes experienced a significantly higher infection rate than those without prophylactic measures. 7此外，一项研究表明，患者接受杆菌肽刷新经历了那些没有预防措施，显着高于高感染率。 七
Prophylactic antibiotic use in patients with TBI have shown no meaningful reduction in nosocomial infections. 7 In addition, an increase in serious gram-negative infections was noted in this population.与颅脑创伤患者预防性使用抗生素在院内感染没有表现出有意义的减少英寸另外7在，增加了感染的严重革兰阴性是人口注意到这一点。 The guidelines also cite data showing an increase in resistant or gram-negative nosocomial pneumonias.该准则还举出数据显示，在抗或革兰氏阴性院内肺炎增加。 This was seen when prophylactic antibiotics were given for longer than 48 hours in general trauma patients.这被看作是作预防性抗生素时不超过48小时，一般外伤患者给予。 In contrast, one study showed a decrease in pneumonias when prophylactic antibiotics were given to patients with TBI.相反，一项研究显示，减少肺炎时给予预防性抗生素与脑外伤病人。 No difference in mortality was noted, so it is difficult to assess the usefulness of this therapeutic avenue. 7没有死亡率的差异在会上指出，因此很难评估这种治疗有效性的途径。 七
Since publication of the 2007 guidelines, one further study in patients with TBI has been completed. 8 This study retrospectively evaluated the use of antibiotic prophylaxis in patients with ICP monitor implantation.自2007年出版的准则，其中一人头部外伤病人的进一步研究工作已经完成。8本研究回顾性评价了植入颅内压监测与使用抗生素预防患者。 Of the 155 patients included in the analysis, only two developed CNS infections, and these were both in the group that received prophylactic antibiotics.对155例患者的分析中，只有两个发达国家中枢神经系统感染，而这些都在预防性抗生素组收到了。 Additionally, both complications from infections and multidrug resistant infections were significantly increased in the group that received antibiotics.此外，无论从感染并发症及耐药性感染显着增加了组收到的抗生素。
In summary, there are currently no convincing data to support infection prophylaxis in patients with TBI, especially in light of data suggesting that prophylaxis might predispose patients to more severe infections when infections would arise. 7,8 To be fair, there is a relative lack of data to give any definitive statement on the use of prophylactic antibiotics, but at this time this practice cannot be supported.总之，目前没有任何令人信服的数据，以支持在预防脑外伤感染患者，尤其是在光线会出现的数据表明预防有可能使患者容易感染时更严重的感染。7,8公平地说，有一个相对缺乏数据提供任何有关预防性使用抗生素的明确声明，但在这种做法是不能支持的时间。
Venous Thromboembolism Prophylaxis静脉血栓栓塞症的预防
Venous thromboembolism (VTE) is a topic that is very pertinent to patients with TBI, as they are at an increased risk of developing blood clots due to their typically persistent immobile state.静脉血栓（VTE）是一个主题，这是非常中肯与头部外伤病人，因为他们在发展中的一个血块，因为它们通常不动的状态持续上升的风险。 The development of deep vein thrombosis (DVT) in patients with TBI who do not receive prophylaxis is as high as 25%. 9 However, there remains some uncertainty about the appropriateness of VTE prophylaxis due to the questionable safety of anticoagulation in patients who have TBI.颅脑创伤发展的深部静脉血栓形成（DVT）与病人谁不接受预防是高达25％。9然而，仍然存在一些不确定性谁是合适的患者抗凝预防静脉血栓栓塞的安全性问题因脑外伤。 Mechanical means of VTE prophylaxis such as sequential compression devices seem to carry less risk in patients with TBI, but concomitant lower limb injuries can prevent their use in some patients.机械职业教育预防手段，如连续进行压缩设备似乎少与颅脑创伤患者的风险，但随之而来的下肢伤害可以防止他们在某些病人使用。 Per the 2007 guidelines, mechanical VTE prophylaxis is recommended in all severe patients with TBI who have no contraindications to usage, such as an intracranial bleed. 10 2007年每准则，机械静脉血栓栓塞预防建议到使用，所有重型颅脑创伤患者谁没有禁忌症，如颅内出血。10
Concerning pharmacologic options, the guidelines suggest that low-molecular-weight heparin (LMWH) or low-dose unfractionated heparin (UFH) should be used in addition to mechanical means of VTE prophylaxis when no contraindications to LMWH or UFH exist.关于药理选项，指引表明，低分子量肝素（LMWH）或低剂量普通肝素（UFH的）应该是除机械职业教育预防手段时没有低分子肝素或普通肝素的禁忌存在。 It is important to note, however, that the guidelines do not elicit a preferred agent, dosage, or timing of pharmacologic prophylaxis and also warn of the increased risk of intracranial hemorrhage expansion. 10重要的是要注意，但是，这些准则并没有引起首选剂，剂量，或预防措施的时机也警告的药理和扩张的出血风险增加颅内。10
Three studies have been published since the guidelines on pharmacologic VTE prophylaxis in patients with TBI. 11-13 A 2007 prospective study evaluated the use of dalteparin in trauma patients in which 23% were patients with TBI. 11 These patients received prophylactic dalteparin (5,000 units SQ once daily) if there was no active or progressing bleed on CT scan. 3项研究已发表与脑外伤后患者的预防指引，职业教育在药理。11-13 2007年的前瞻性研究评估了颅脑创伤使用阿昔洛韦创伤患者，其中23％的的病人。11这些患者接受预防性阿昔洛韦（5,000个单位智商每日一次），如果没有积极的进展或出血的CT扫描。 No patients developed or had increased intracranial bleeding after initiation of dalteparin, while only 3.9% of patients had evidence of DVT and 0.8% had evidence of pulmonary embolism.无1例是发达国家还是增加了启动后，阿昔洛韦颅内出血，而只有3.9％的患者深静脉血栓形成的证据和0.8％的人肺动脉栓塞的证据。 A second prospective study published in 2008 evaluated the use of enoxaparin (30 mg SQ twice daily) in patients with TBI. 12 Progressive hemorrhagic injury was seen in 3.4% of the TBI population, with 67% of those patients having clinically insignificant hemorrhagic changes.第二项前瞻性研究中评估了2008年出版使用依诺肝素（30毫克，每日两次平方脑外伤）的患者。12进出血损伤主要出现在3.4％的人口变化的脑外伤，失血性微不足道的67％的病人有临床。 In addition, one patient died from a potential side effect from enoxaparin usage.此外，1例死于由依诺肝素的使用潜在的副作用。 The authors of these two studies concluded that enoxaparin and dalteparin are safe options in patients with TBI and that both agents have a relatively low risk of significant bleeding complications. 11,12在这些研究的结论提交两个与依诺肝素和阿昔洛韦颅脑创伤患者选择安全，而且在这两种药物有显着的出血并发症的风险相对较低。11,12
A retrospective study published in 2009 looked at a comparison of the risk of DVT in patients with and without TBI utilizing either LMWH or UFH (doses not specified). 13 This study showed a three- to fourfold increase in DVTs in patients with TBI using relative risks with 95% confidence intervals.回顾分析2009年出版的看着一个比较深静脉血栓患者的风险和不使用任何头部外伤低分子肝素或普通肝素（指定剂量不）。13本研究显示三至四倍TBI的增加与患者在使用相对DVTs风险，95％的置信区间。 The highest rate was noted when prophylaxis was started greater than 48 hours after insult.发病率最高的是预防时指出大于48小时后开始的侮辱。
In summary, it is currently acceptable to recommend mechanical and pharmacologic VTE prophylaxis in patients with TBI that have no contraindications to usage. 10-13 The evidence is shifting in favor of quick initiation of prophylactic agents regardless of product selection.总之，它目前正在接受推荐使用上没有任何禁忌和药理学机制上预防静脉血栓栓塞患者头部外伤。10-13证据是代理人在开展预防性转移迅速失宠不管产品的选择。 However, the breakpoint for deciding between mechanical and pharmacologic choices or agents is still unknown and should be a course of future study.但是，机械和药理学之间的选择或代理人仍是未知的，应是今后的研究方向决定断点。
Seizure Prophylaxis海关检获预防
Posttraumatic seizure (PTS) is a common occurrence in patients with TBI.外伤性癫痫（PTS）为一个与颅脑创伤患者屡见不鲜。 These seizures are broken into two groups: early (within 7 days of injury) and late (after 7 days).这些缉获分为两组：早期（伤后7天）和晚期（后7天）。 Certain risk factors have been shown to place patients with TBI at increased risk for PTS.某些风险因素已被证明在地方与脑外伤患者的PTS风险增加。 These risk factors include: Glasgow Coma Score (a neurological scale used to assess level of consciousness) less than 10; cortical contusion; depressed skull fracture; subdural, intracerebral, and epidural hematoma; penetrating head wound; or seizure within 24 hours after injury. 14这些风险因素包括：格拉斯哥昏迷评分（1神经规模用于评估小于10;皮质挫伤;凹陷性颅骨骨折，硬膜下，脑内血肿，硬膜外;穿透头部受伤，或在24小时内发作的意识水平）伤后。 14
Phenytoin and valproate sodium have been studied in the prevention of early and late PTS.苯妥英钠和丙戊酸钠进行了研究在早期和晚期警校预防。 One study cited by the 2007 guidelines showed a significant reduction in early PTS without showing any significant effect on late PTS or survival with the use of phenytoin. 14 In contrast, a randomized, double-blind study showed no early or late PTS benefit by using phenytoin.引述一项研究显示，由2007年的指导方针生存与使用苯妥英的重大晚在警校或减少早期警校没有显示任何重大影响。14相反，随机，双盲研究显示，没有早或晚使用警校受益苯妥英。 Valproate sodium has shown a similar rate of early PTS reduction when compared to phenytoin.丙戊酸钠已经表现出了类似的早期警校率降低相比，苯妥英。 However, a trend toward higher mortality in the valproate sodium group was noted and could be cause for concern. 14然而，一组高死亡率的趋势对钠丙戊酸钠在会上指出，可担心的。 十四
Since the publication of the guidelines, there have been two pertinent studies completed regarding seizure prophylaxis. 15-16 The first, a study from 2008, compared the incidence of seizures in patients with TBI when randomized to either phenytoin or levetiracetam. 15 Results indicated that there was no significant difference in seizure incidence.由于出版的指引，有两个相关的研究，完成了关于预防发作。15-16第一，从2008年的一项研究，比较了颅脑创伤的发生率与患者在发作时，随机分为苯妥英或左乙拉西坦。结果表明，15有没有发作的发生率显着差异。 However, patients receiving levetiracetam showed increased incidence of electroencephalogram (EEG) abnormalities.然而，左乙拉西坦显示患者接受脑电图发生率增加（脑电图）异常。 An EEG was indicated if patients displayed persistent coma, decreased mental status, or clinical signs of seizures.与会者指出，如果一个患者脑电图显示持续昏迷，精神状况，或发作的症状。
The second study evaluated the incidence of late PTS in patients with TBI who did or did not receive antiseizure prophylaxis upon initial presentation. 16 This study was carried out in Italy, with phenobarbital being one of the main agents used in antiseizure prophylaxis.第二项研究评估了颅脑创伤患者的发病率与警校下旬谁没有或没有接受抗抽搐预防本研究在初步报告。16在意大利进行，与苯巴比妥预防1被用于抗癫痫药物的主要。 Interestingly, in the retrospective portion of the study, 29% of patients who received antiseizure prophylaxis developed late PTS, while only 13% of patients who did not receive prophylaxis developed late PTS.有趣的是，在这项研究中，29例接受抗抽搐预防谁开发后期警校，％追溯部分，而只有13％的患者未接受谁开发后期警校预防。 While the retrospective data were not statistically significant, the prospective data were even more striking.虽然追溯的数据在统计学上没有显着，未来的数据更是惊人的。 A significant difference was noted in the prospective group, where 39% of patients treated with antiseizure prophylaxis developed late PTS, while none of the patients who were not treated with antiseizure prophylaxis developed late PTS.一个显着性差异注意到准组，其中以抗39％的患者制定预防治疗晚期警校，而没有对谁不发达国家与抗癫痫预防治疗晚期警校的病人。 However, phenobarbital is not commonly used in the US in this regard because of its adverse-effect profile and multiple drug interactions, and because more appropriate antiepileptic selections are available; therefore, results must not be generalized too drastically.然而，苯巴比妥不常用在美国这是因为其不利效应形象和多种药物的相互作用方面，由于更多的选择，可适当抗癫痫药物，因此，结果不能概括得太过分。
In summary, current literature including the 2007 guidelines indicates that the incidence of early PTS appears to be reduced with the addition of prophylactic antiseizure medications. 14 However, there is currently no evidence to indicate that prophylactic antiseizure medications alter mortality or incidence of late PTS, and it is still unknown whether or not this course of therapeutic prophylaxis is currently benefitting patients.总之，目前的文献，包括2007年的指导方针表明，警校发病早期似乎与抗癫痫药物降低预防性的加法。14然而，目前还没有证据表明，预防性抗癫痫药物改变警察训练学校发生死亡或晚，它目前仍是未知之患者是否受益这不是治疗预防课程。
Conclusion结论
Traumatic brain injury can be overwhelming and distressing to both patients and their family members.外伤性脑损伤可以变得十分艰巨和痛苦的病人和他们的家属。 In addition to the emotional and social impacts that accompany TBI, it is important to identify and deliver prompt attention to the physical needs of the patient.除了情绪和社会影响，伴随头部外伤，重要的是要确定和提供及时注意病人的身体的需要。 Prophylactic medications play an important role in patients with TBI, yet as of now many categories lack definitive data to direct appropriate therapeutic choices.预防性药物在发挥脑外伤患者的重要作用，但由于目前缺乏明确的数据，许多类别直接适当的治疗选择。 Future studies are needed to clarify this important issue in the management of patients with this condition.未来的研究需要澄清的病人管理这个条件这一重要问题。
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