今日の臨床サポート

重症頭部外傷

著者: 瀬良誠 福井県立病院 救命救急センター

監修: 林寛之 福井大学医学部附属病院

著者校正/監修レビュー済:2020/03/12
参考ガイドライン:
  1. Guidelines for the Management of Severe Traumatic Brain Injury 第4版
  1. 頭部外傷治療・管理のガイドライン(第4版)
患者向け説明資料

概要・推奨   

  1. 重症頭部外傷はまだ確立されたエビデンスが乏しく、国内外のガイドラインでは「すべきこと」よりも「避けること」「してはいけないこと」に重点がおかれている。
  1. 重症頭部外傷では2次性脳損傷の予防に重点がおかれる。
  1. 低血圧(収縮期血圧110~120mmHg)と低酸素(SpO290%)は明らかな予後不良因子のため、これらを回避することに細心の注意を要する。
  1. 閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契約が 必要となります。 閲覧にはご契 約が必要となります。 閲覧に はご契約が必要となります。閲覧にはご契約が必
  1. 閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご
薬剤監修について:
オーダー内の薬剤用量は日本医科大学付属病院 薬剤部 部長 伊勢雄也 以下、林太祐、渡邉裕次、井ノ口岳洋、梅田将光による疑義照会のプロセスを実施、疑義照会の対象については著者の方による再確認を実施しております。
※薬剤中分類、用法、同効薬、診療報酬は、エルゼビアが独自に作成した薬剤情報であり、
著者により作成された情報ではありません。
尚、用法は添付文書より、同効薬は、薬剤師監修のもとで作成しております。
※薬剤情報の(適外/適内/⽤量内/⽤量外/㊜)等の表記は、エルゼビアジャパン編集部によって記載日時にレセプトチェックソフトなどで確認し作成しております。ただし、これらの記載は、実際の保険適用の査定において保険適用及び保険適用外と判断されることを保証するものではありません。また、検査薬、輸液、血液製剤、全身麻酔薬、抗癌剤等の薬剤は保険適用の記載の一部を割愛させていただいています。
(詳細はこちらを参照)
著者のCOI(Conflicts of Interest)開示:
瀬良誠 : 特に申告事項無し[2021年]
監修:林寛之 : 講演料(メディカ出版),原稿料(羊土社)[2021年]

改訂のポイント:
  1. 頭部外傷治療・管理のガイドラインの改訂に伴い、Guidelines for the Management of Severe Traumatic Brain Injuryに基づくエビデンス文にこの日本のガイドラインの推奨を対比できるように追記した。
  1. 今回の頭部外傷治療・管理のガイドラインの改訂ポイントは以下である。
  1. 「頭部外傷に伴う凝固線溶系障害」、「早期リハビリテーション」、「外傷急性期の精神障害」、「多発外傷」の4項目が新規に追加された。
  1. 「小児・高齢者重症頭部外傷」がその内容の充実とともに対象患者の広がりに合わせて「小児頭部外傷」と「高齢者頭部外傷」の2項目へ変更された。

病態・疫学・診察

疫学情報・病態・注意事項  
  1. 頭部外傷は米国では年間140万人、そのうち110万人が救急受診し入院が23万5000人に上る。
  1. 原因としては主に以下が挙げられる。
  1. 転落:28%(0~4歳と75歳以上に多い)
  1. 交通事故:20%(15~19歳に多い)
  1. 米国では頭部外傷で年間5万人が死亡し、鈍的外傷による死亡率は頭部外傷がなければ1%、あれば30%にまで跳ね上がる。
  1. 重症頭部外傷とはGlasgow Coma Scale(GCS)8以下を指し、頭部外傷の約10%を占める。
  1. 重症頭部外傷では2次性脳損傷を予防することに重点が置かれ、下記の状態を回避することを目標とする。特に低血圧と低酸素は明らかな予後不良因子であるため、治療の際には細心の注意を要する。収縮期血圧下限閾値については90mmHgでは低すぎるという報告も多く、110~120mmHgを目標下限閾値としたほうがよい。
  1. 低血圧(収縮期血圧[SBP]<110mmHg)
  1. 低酸素(SpO2<90%)
  1. 低炭酸ガス血症(PaCO2<35mmHg)
  1. 発熱(BT>38℃)
  1. 凝固異常
  1. 貧血
  1. 重症頭部外傷では他部位の外傷を合併していることが多く(35~60%)、特にバイタルサインに異常がある(ショックバイタル)場合、頭部外傷以外の原因検索を必ず行う。 >詳細情報  >詳細情報 
 
  1. 65歳以上の高齢者における単独重症頭部外傷では65歳未満と比べGlasgow Coma Scale(GCS)が高い傾向にある。そのため高齢者の頭部外傷にGCSをトリアージ手段として利用する場合は注意が必要である(推奨度2)
  1. 561人の単独頭部外傷患者を65歳で区切り、65歳未満群244人、65歳以上群317人でそれらの来院時GCSとabbreviated injury scale(AIS)の関連を調べた[1]
  1. AISとは解剖学的な重症度のことをいい、AIS3~5で重症、例えばAIS3で頭蓋底骨折、AIS4で硬膜下血腫(≦50cm3)、AIS5で巨大硬膜外血腫である。
  1. 来院時GCSが3~8の65歳以上の重症頭部外傷患者は9.8%(65歳未満では22.1%)にも関わらず、AIS5の65歳以上の患者は45.1%(65歳未満では37.3%)であった。
  1. 死亡患者では65歳以上群の来院時GCS11(中央値)であり、65歳未満群の来院時GCS4.5(中央値)に比べ有意に高かった。
  1. 6,710人の頭部外傷患者(他部位の外傷含む)を65歳で区切り、65歳未満群4,910人、65歳以上群1,800人でGCSとAISの関連を調べた[2]
  1. AIS5かつGCS3~8の患者は65歳以上では30.57%(65歳未満では63.28%)であったが、逆にAIS5かつGCS13~15の患者は65歳以上では56.33%(65歳未満では28.53%)であり、65歳以上の高齢者をGCSで評価すると重症度を過小評価される傾向にあった。しかし、この研究では死亡率については年齢とAISあるいはGCSとの関連を認めなかった。
問診・診察のポイント  
  1. 問診ではAMPLE(allergies, medications, past medical history, last meal, events/environment related to the injury)の聴取を行い、受傷機転や意識消失の有無、けいれんの有無、アルコールあるいはドラッグの使用についても適宜追加聴取する。

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文献 

著者: A Kehoe, S Rennie, J E Smith
雑誌名: Emerg Med J. 2015 Aug;32(8):613-5. doi: 10.1136/emermed-2013-203488. Epub 2014 Oct 3.
Abstract/Text OBJECTIVES AND BACKGROUND: Elderly patients comprise an ever-increasing proportion of major trauma patients. The presenting GCS in elderly patients with traumatic brain injury (TBI) may not reflect the severity of injury as accurately as it does in the younger patient population. However, GCS is often used as part of the decision tool to define the population transferred directly to a major trauma centre. The aim of this study was to explore the relationship between age and presenting GCS in patients with isolated TBI.
METHODS: A retrospective database review was undertaken using the Trauma Audit and Research Network database. All patients presenting to Derriford Hospital, Plymouth, between 1 January 2009 and 31 May 2014 with isolated TBI were included. Demographic, mechanistic, physiological, resource use and outcome data were collected. Abbreviated injury scale (AIS) was recorded for all patients. Patients were categorised into those older and younger than 65 years on presentation. Distribution of GCS, categorised into severe (GCS 3-8), moderate (GCS 9-12) and mild TBI (13-15), was compared between the age groups. Median GCS at each AIS level was also compared.
RESULTS: The distribution of GCS differed between young and old patients with TBI (22.1% vs 9.8% had a GCS 3-8, respectively) despite a higher burden of anatomical injury in the elderly group. Presenting GCS was higher in the elderly at each level of AIS. The difference was more apparent in the presence of more severe injury (AIS 5).
CONCLUSIONS: Elderly patients who have sustained isolated severe TBI may present with a higher GCS than younger patients. Triage tools using GCS may need to be modified and validated for use in elderly patients with TBI.

Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.
PMID 25280479  Emerg Med J. 2015 Aug;32(8):613-5. doi: 10.1136/emermed・・・
著者: Kristin Salottolo, A Stewart Levy, Denetta S Slone, Charles W Mains, David Bar-Or
雑誌名: JAMA Surg. 2014 Jul;149(7):727-34. doi: 10.1001/jamasurg.2014.13.
Abstract/Text IMPORTANCE: The Glasgow Coma Scale (GCS) is used frequently to define the extent of neurologic injury in patients with a traumatic brain injury (TBI). Whether age affects the predictive ability of the GCS for severity of TBI (determined by the Abbreviated Injury Scale [AIS] score) remains unknown.
OBJECTIVE: To investigate the effect of age on the association between the GCS and anatomic TBI severity.
DESIGN, SETTING, AND PARTICIPANTS: We examined all patients with a TBI, defined by diagnostic codes 850 to 854 from the International Classification of Diseases, Ninth Revision, Clinical Modification, who were admitted to 2 level I trauma centers from January 1, 2008, through December 31, 2012.
EXPOSURES: We compared elderly (≥65 years) and younger (18-64 years) adults with TBI.
MAIN OUTCOMES AND MEASURES: We examined differences by age in GCS category (defined by emergency department GCS as severe [3-8], moderate [9-12], or mild [13-15]) at each level of TBI severity (head AIS score, 1 [minor] to 5 [critical]). Cochran-Armitage χ² trend tests and stepwise multivariate linear and logistic regression models were used.
RESULTS: During the study period, 6710 patients had a TBI (aged <65 years, 73.17%). Significant differences in GCS category by age occurred at each AIS score (P ≤ .01 for all). In particular, among patients with an AIS score of 5, most of the elderly patients (56.33%) had a mild neurologic deficit (GCS score, 13-15), whereas most of the younger patients (63.28%) had a severe neurologic deficit (GCS score, 3-8). After adjustment, the younger adults had increased odds of presenting with a severe neurologic deficit (GCS score, 3-8) at each of the following AIS scores: 1, 4.2 (95% CI, 1.0-17.6; P = .05); 2, 2.0 (1.0-3.7; P = .04); 3, 2.0 (1.2-3.5; P = .01); 4, 4.6 (2.8-7.5; P < .001); and 5, 3.1 (2.1-4.6; P < .001). The interaction between age and GCS for anatomic TBI severity remained significant after adjustment (estimate, -0.11; P = .005).
CONCLUSIONS AND RELEVANCE: Age affects the relationship between the GCS score and anatomic TBI severity. Elderly TBI patients have better GCS scores than younger TBI patients with similar TBI severity. These findings have implications for TBI outcomes research and for protocols and research selection criteria that use the GCS.

PMID 24899145  JAMA Surg. 2014 Jul;149(7):727-34. doi: 10.1001/jamasur・・・
著者: Daniel W Spaite, Chengcheng Hu, Bentley J Bobrow, Vatsal Chikani, Duane Sherrill, Bruce Barnhart, Joshua B Gaither, Kurt R Denninghoff, Chad Viscusi, Terry Mullins, P David Adelson
雑誌名: JAMA Surg. 2017 Apr 1;152(4):360-368. doi: 10.1001/jamasurg.2016.4686.
Abstract/Text Importance: Current prehospital traumatic brain injury guidelines use a systolic blood pressure threshold of less than 90 mm Hg for treating hypotension for individuals 10 years and older based on studies showing higher mortality when blood pressure drops below this level. However, the guidelines also acknowledge the weakness of the supporting evidence.
Objective: To evaluate whether any statistically supportable threshold between systolic pressure and mortality emerges from the data a priori, without assuming that a cut point exists.
Design, Setting, and Participants: Observational evaluation of a large prehospital database established as a part of the Excellence in Prehospital Injury Care Traumatic Brain Injury Study. Patients from the preimplementation cohort (January 2007 to March 2014) 10 years and older with moderate or severe traumatic brain injury (Barell Matrix Type 1 classification, International Classification of Diseases, Ninth Revision head region severity score of 3 or greater, and/or Abbreviated Injury Scale head-region severity score of 3 or greater) and a prehospital systolic pressure between 40 and 119 mm Hg were included. The generalized additive model and logistic regression were used to determine the association between systolic pressure and probability of death, adjusting for significant/important confounders.
Main Outcomes and Measures: The main outcome measure was in-hospital mortality.
Results: Among the 3844 included patients, 2565 (66.7%) were male, and the median (range) age was 35 (10-99) years. The model revealed a monotonically decreasing association between systolic pressure and adjusted probability of death across the entire range (ie, from 40 to 119 mm Hg). Each 10-point increase of systolic pressure was associated with a decrease in the adjusted odds of death of 18.8% (adjusted odds ratio, 0.812; 95% CI, 0.748-0.883). Thus, the adjusted odds of mortality increased as much for a drop from 110 to 100 mm Hg as for a drop from 90 to 80 mm Hg, and so on throughout the range.
Conclusions and Relevance: We found a linear association between lowest prehospital systolic blood pressure and severity-adjusted probability of mortality across an exceptionally wide range. There is no identifiable threshold or inflection point between 40 and 119 mm Hg. Thus, in patients with traumatic brain injury, the concept that 90 mm Hg represents a unique or important physiological cut point may be wrong. Furthermore, clinically meaningful hypotension may not be as low as current guidelines suggest. Randomized trials evaluating treatment levels significantly above 90 mm Hg are needed.

PMID 27926759  JAMA Surg. 2017 Apr 1;152(4):360-368. doi: 10.1001/jama・・・
著者: A I Maas, M Dearden, G M Teasdale, R Braakman, F Cohadon, F Iannotti, A Karimi, F Lapierre, G Murray, J Ohman, L Persson, F Servadei, N Stocchetti, A Unterberg
雑誌名: Acta Neurochir (Wien). 1997;139(4):286-94.
Abstract/Text Guidelines for the management of severe head injury in adults as evolved by the European Brain Injury Consortium are presented and discussed. The importance of preventing and treating secondary insults is emphasized and the principles on which treatment is based are reviewed. Guidelines presented are of a pragmatic nature, based on consensus and expert opinion, covering the treatment from accident site to intensive care unit. Specific aspects pertaining to the conduct of clinical trials in head injury are highlighted. The adopted approach is further discussed in relation to other approaches to the development of guidelines, such as evidence based analysis.

PMID 9202767  Acta Neurochir (Wien). 1997;139(4):286-94.
著者: Daniel W Spaite, Chengcheng Hu, Bentley J Bobrow, Vatsal Chikani, Bruce Barnhart, Joshua B Gaither, Kurt R Denninghoff, P David Adelson, Samuel M Keim, Chad Viscusi, Terry Mullins, Amber D Rice, Duane Sherrill
雑誌名: Ann Emerg Med. 2017 Oct;70(4):522-530.e1. doi: 10.1016/j.annemergmed.2017.03.027. Epub 2017 May 27.
Abstract/Text STUDY OBJECTIVE: Out-of-hospital hypotension has been associated with increased mortality in traumatic brain injury. The association of traumatic brain injury mortality with the depth or duration of out-of-hospital hypotension is unknown. We evaluated the relationship between the depth and duration of out-of-hospital hypotension and mortality in major traumatic brain injury.
METHODS: We evaluated adults and older children with moderate or severe traumatic brain injury in the preimplementation cohort of Arizona's statewide Excellence in Prehospital Injury Care study. We used logistic regression to determine the association between the depth-duration dose of hypotension (depth of systolic blood pressure <90 mm Hg integrated over duration [minutes] of hypotension) and odds of inhospital death, controlling for significant confounders.
RESULTS: There were 7,521 traumatic brain injury cases included (70.6% male patients; median age 40 years [interquartile range 24 to 58]). Mortality was 7.8% (95% confidence interval [CI] 7.2% to 8.5%) among the 6,982 patients without hypotension (systolic blood pressure ≥90 mm Hg) and 33.4% (95% CI 29.4% to 37.6%) among the 539 hypotensive patients (systolic blood pressure <90 mm Hg). Mortality was higher with increased hypotension dose: 0.01 to 14.99 mm Hg-minutes 16.3%; 15 to 49.99 mm Hg-minutes 28.1%; 50 to 141.99 mm Hg-minutes 38.8%; and greater than or equal to 142 mm Hg-minutes 50.4%. Log2 (the logarithm in base 2) of hypotension dose was associated with traumatic brain injury mortality (adjusted odds ratio 1.19 [95% CI 1.14 to 1.25] per 2-fold increase of dose).
CONCLUSION: In this study, the depth and duration of out-of-hospital hypotension were associated with increased traumatic brain injury mortality. Assessments linking out-of-hospital blood pressure with traumatic brain injury outcomes should consider both depth and duration of hypotension.

Copyright © 2017 American College of Emergency Physicians. Published by Elsevier Inc. All rights reserved.
PMID 28559036  Ann Emerg Med. 2017 Oct;70(4):522-530.e1. doi: 10.1016/・・・
著者: CRASH-3 trial collaborators
雑誌名: Lancet. 2019 Nov 9;394(10210):1713-1723. doi: 10.1016/S0140-6736(19)32233-0. Epub 2019 Oct 14.
Abstract/Text BACKGROUND: Tranexamic acid reduces surgical bleeding and decreases mortality in patients with traumatic extracranial bleeding. Intracranial bleeding is common after traumatic brain injury (TBI) and can cause brain herniation and death. We aimed to assess the effects of tranexamic acid in patients with TBI.
METHODS: This randomised, placebo-controlled trial was done in 175 hospitals in 29 countries. Adults with TBI who were within 3 h of injury, had a Glasgow Coma Scale (GCS) score of 12 or lower or any intracranial bleeding on CT scan, and no major extracranial bleeding were eligible. The time window for eligibility was originally 8 h but in 2016 the protocol was changed to limit recruitment to patients within 3 h of injury. This change was made blind to the trial data, in response to external evidence suggesting that delayed treatment is unlikely to be effective. We randomly assigned (1:1) patients to receive tranexamic acid (loading dose 1 g over 10 min then infusion of 1 g over 8 h) or matching placebo. Patients were assigned by selecting a numbered treatment pack from a box containing eight packs that were identical apart from the pack number. Patients, caregivers, and those assessing outcomes were masked to allocation. The primary outcome was head injury-related death in hospital within 28 days of injury in patients treated within 3 h of injury. We prespecified a sensitivity analysis that excluded patients with a GCS score of 3 and those with bilateral unreactive pupils at baseline. All analyses were done by intention to treat. This trial was registered with ISRCTN (ISRCTN15088122), ClinicalTrials.gov (NCT01402882), EudraCT (2011-003669-14), and the Pan African Clinical Trial Registry (PACTR20121000441277).
RESULTS: Between July 20, 2012, and Jan 31, 2019, we randomly allocated 12 737 patients with TBI to receive tranexamic acid (6406 [50·3%] or placebo [6331 [49·7%], of whom 9202 (72·2%) patients were treated within 3 h of injury. Among patients treated within 3 h of injury, the risk of head injury-related death was 18·5% in the tranexamic acid group versus 19·8% in the placebo group (855 vs 892 events; risk ratio [RR] 0·94 [95% CI 0·86-1·02]). In the prespecified sensitivity analysis that excluded patients with a GCS score of 3 or bilateral unreactive pupils at baseline, the risk of head injury-related death was 12·5% in the tranexamic acid group versus 14·0% in the placebo group (485 vs 525 events; RR 0·89 [95% CI 0·80-1·00]). The risk of head injury-related death reduced with tranexamic acid in patients with mild-to-moderate head injury (RR 0·78 [95% CI 0·64-0·95]) but not in patients with severe head injury (0·99 [95% CI 0·91-1·07]; p value for heterogeneity 0·030). Early treatment was more effective than was later treatment in patients with mild and moderate head injury (p=0·005) but time to treatment had no obvious effect in patients with severe head injury (p=0·73). The risk of vascular occlusive events was similar in the tranexamic acid and placebo groups (RR 0·98 (0·74-1·28). The risk of seizures was also similar between groups (1·09 [95% CI 0·90-1·33]).
INTERPRETATION: Our results show that tranexamic acid is safe in patients with TBI and that treatment within 3 h of injury reduces head injury-related death. Patients should be treated as soon as possible after injury.
FUNDING: National Institute for Health Research Health Technology Assessment, JP Moulton Charitable Trust, Department of Health and Social Care, Department for International Development, Global Challenges Research Fund, Medical Research Council, and Wellcome Trust (Joint Global Health Trials scheme).
TRANSLATIONS: For the Arabic, Chinese, French, Hindi, Japanese, Spanish and Urdu translations of the abstract see Supplementary Material.

Copyright © 2019 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.
PMID 31623894  Lancet. 2019 Nov 9;394(10210):1713-1723. doi: 10.1016/S・・・
著者: Nancy Carney, Annette M Totten, Cindy O'Reilly, Jamie S Ullman, Gregory W J Hawryluk, Michael J Bell, Susan L Bratton, Randall Chesnut, Odette A Harris, Niranjan Kissoon, Andres M Rubiano, Lori Shutter, Robert C Tasker, Monica S Vavilala, Jack Wilberger, David W Wright, Jamshid Ghajar
雑誌名: Neurosurgery. 2017 Jan 1;80(1):6-15. doi: 10.1227/NEU.0000000000001432.
Abstract/Text The scope and purpose of this work is 2-fold: to synthesize the available evidence and to translate it into recommendations. This document provides recommendations only when there is evidence to support them. As such, they do not constitute a complete protocol for clinical use. Our intention is that these recommendations be used by others to develop treatment protocols, which necessarily need to incorporate consensus and clinical judgment in areas where current evidence is lacking or insufficient. We think it is important to have evidence-based recommendations to clarify what aspects of practice currently can and cannot be supported by evidence, to encourage use of evidence-based treatments that exist, and to encourage creativity in treatment and research in areas where evidence does not exist. The communities of neurosurgery and neuro-intensive care have been early pioneers and supporters of evidence-based medicine and plan to continue in this endeavor. The complete guideline document, which summarizes and evaluates the literature for each topic, and supplemental appendices (A-I) are available online at https://www.braintrauma.org/coma/guidelines.

Copyright © 2016 Brain Trauma Foundation.
PMID 27654000  Neurosurgery. 2017 Jan 1;80(1):6-15. doi: 10.1227/NEU.0・・・
著者: Marek Majdan, Walter Mauritz, Ingrid Wilbacher, Alexandra Brazinova, Martin Rusnak, Johannes Leitgeb
雑誌名: J Neurotrauma. 2013 Jan 1;30(1):23-9. doi: 10.1089/neu.2012.2554. Epub 2012 Dec 6.
Abstract/Text The guidelines for management of traumatic brain injury (TBI) recommend that high-dose barbiturate therapy may be considered to lower intracranial pressure (ICP) that is refractory to other therapeutic options. Lower doses of barbiturates may be used for sedation of patients with TBI, although there is no mention of this in the published guidelines. The goal of this study was to analyze the use of barbiturates in patients with severe TBI in the European centers where the International Neurotrauma Research Organization introduced guideline-based TBI management and to analyze the effects of barbiturates on ICP, use of vasopressors, and short- and long-term outcome of these patients. Data on 1172 patients with severe TBI were collected in 13 centers located in five European countries. Patients were categorized into three groups based on doses of barbiturates administered during treatment. Univariate and multivariate statistical methods were used to analyze the effects of barbiturates on the outcome of patients. Fewer than 20% of all patients with severe TBI were given barbiturates overall, and only 6% was given high doses. High-dose barbiturate treatment caused a decrease in ICP in 69% of patients but also caused hemodynamic instability leading to longer periods of mean arterial pressure <70 mm Hg despite increased use of high doses of vasopressors. The adjusted analysis showed no significant effect on outcome on any stage after injury.Thiopental and methohexital were equally effective. Low doses of thiopental and methohexital were used for sedation of patients without side effects. Phenobarbital was probably used for prophylaxis of post-traumatic seizures.

PMID 22950895  J Neurotrauma. 2013 Jan 1;30(1):23-9. doi: 10.1089/neu.・・・
著者: Jon Pérez-Bárcena, Juan A Llompart-Pou, Javier Homar, Josep M Abadal, Joan M Raurich, Guillem Frontera, Marta Brell, Javier Ibáñez, Jordi Ibáñez
雑誌名: Crit Care. 2008;12(4):R112. doi: 10.1186/cc6999. Epub 2008 Aug 29.
Abstract/Text INTRODUCTION: Experimental research has demonstrated that the level of neuroprotection conferred by the various barbiturates is not equal. Until now no controlled studies have been conducted to compare their effectiveness, even though the Brain Trauma Foundation Guidelines recommend that such studies be undertaken. The objectives of the present study were to assess the effectiveness of pentobarbital and thiopental in terms of controlling refractory intracranial hypertension in patients with severe traumatic brain injury, and to evaluate the adverse effects of treatment.
METHODS: This was a prospective, randomized, cohort study comparing two treatments: pentobarbital and thiopental. Patients who had suffered a severe traumatic brain injury (Glasgow Coma Scale score after resuscitation < or = 8 points or neurological deterioration during the first week after trauma) and with refractory intracranial hypertension (intracranial pressure > 20 mmHg) first-tier measures, in accordance with the Brain Trauma Foundation Guidelines.
RESULTS: A total of 44 patients (22 in each group) were included over a 5-year period. There were no statistically significant differences in ' baseline characteristics, except for admission computed cranial tomography characteristics, using the Traumatic Coma Data Bank classification. Uncontrollable intracranial pressure occurred in 11 patients (50%) in the thiopental treatment group and in 18 patients (82%) in the pentobarbital group (P = 0.03). Under logistic regression analysis--undertaken in an effort to adjust for the cranial tomography characteristics, which were unfavourable for pentobarbital--thiopental was more effective than pentobarbital in terms of controlling intracranial pressure (odds ratio = 5.1, 95% confidence interval 1.2 to 21.9; P = 0.027). There were no significant differences between the two groups with respect to the incidence of arterial hypotension or infection.
CONCLUSIONS: Thiopental appeared to be more effective than pentobarbital in controlling intracranial hypertension refractory to first-tier measures. These findings should be interpreted with caution because of the imbalance in cranial tomography characteristics and the different dosages employed in the two arms of the study. The incidence of adverse effects was similar in both groups.
TRIAL REGISTRATION: (Trial registration: US Clinical Trials registry NCT00622570.).

PMID 18759980  Crit Care. 2008;12(4):R112. doi: 10.1186/cc6999. Epub 2・・・
著者: Wen-Ta Chiu, Tien-Jen Lin, Jia-Wei Lin, Sheng-Jean Huang, Cheng-Kuei Chang, Hsiang-Yin Chen
雑誌名: Surg Neurol. 2006;66 Suppl 2:S37-42. doi: 10.1016/j.surneu.2006.08.028.
Abstract/Text BACKGROUND: The present study was a multicenter, retrospective study which aimed to evaluate the efficacy of propofol, a new choice of pharmacotherapy in head-injured patients.
METHODS: Head-injured patients admitted to 3 hospitals during the period from January 2003 to December 2004 were included in this clinical trial. Data on patients' demographics, laboratory data, GCS score, ICP, CPP, concurrent medications, and therapeutic outcomes were collected.
RESULTS: Among the 104 patients included, only 44 were given propofol. The average age was 40.8 +/- 22 years for all patients, with 41.91 +/- 20.41 and 43.48 +/- 23.19 years for the propofol group and nonpropofol group, respectively (P=.097). There was no significant difference in baseline GCS score between the 2 groups (5.86 +/- 1.84 vs 5.66 +/- 1.59, P=.729). Mean ICP for the first 3 days in the ICU was 17.23 +/- 9.0 mm Hg in the propofol group and 33.19 +/- 32.56 in the nonpropofol group, respectively (P=.017). Mean CPP for the first 5 days in the ICU was 71.10 +/- 15.32 mm Hg in the propofol group and 43.20 +/- 29.92 mm Hg in the nonpropofol group (P<.001). A higher survival rate was found in the propofol group (81.8% vs 46.7%, P<.001).
CONCLUSIONS: The present study demonstrated that propofol improved the outcome in recovery phase of head-injured patients.

PMID 17071254  Surg Neurol. 2006;66 Suppl 2:S37-42. doi: 10.1016/j.sur・・・
著者: Kamran A Ghori, Dominic C Harmon, Abdurrahim Elashaal, Mark Butler, Fergus Walsh, Michael G J O'Sullivan, George D Shorten
雑誌名: Crit Care Resusc. 2007 Jun;9(2):166-71.
Abstract/Text BACKGROUND: Midazolam and propofol are sedative agents commonly administered to patients with brain injury. We compared plasma concentrations of glial cell S100beta protein and nitric oxide (NO) between patients who received midazolam and those who received propofol sedation after severe brain injury, and investigated the association between S100beta and NO concentrations and neurological outcome.
DESIGN: 28 patients with severe head injury (Glasgow Coma Score <9) who required sedation and ventilation were randomly assigned to receive midazolam (n =15) or propofol (n = 13) based sedation. Blood samples were drawn daily for 5 days for estimation of S100beta and NO concentrations. Neurological outcome was assessed 3 months later as good (Glasgow Outcome Score [GOS], 4-5) or poor (GOS, 1-3).
RESULTS: A good neurological outcome was observed in 8/15 patients (53%) in the midazolam group and 7/13 patients (54%) in the propofol group. Patients with a poor outcome had higher serum S100beta concentrations on ICU admission and on Days 1-4 in the ICU than those with a good outcome (mean [SD] on Day 1, 0.99 [0.81] v 0.41 [0.4] microg/L; Day 2, 0.80 [0.81] v 0.41 [0.24] microg/L; Day 3, 0.52 [0.55] v 0.24 [0.25] microg/L; and Day 4, 0.54 [0.43] v 0.24 [0.35] microg/L; P<0.05). There was no significant difference on Day 5. Plasma NO concentrations were not associated with outcome. In subgroup analysis, there was no difference in S100beta and NO concentrations between patients with a good outcome versus those with a poor outcome in either the midazolam or propofol group.
CONCLUSIONS: Plasma concentrations of markers of neurological injury in patients with severe head injury were similar in those who received midazolam sedation and those who received propofol. Patients who had a poor neurological outcome at 3 months had consistently higher serum S100beta concentrations during the initial 4 days after injury than patients who had a good outcome.

PMID 17536986  Crit Care Resusc. 2007 Jun;9(2):166-71.
著者: M L Schwartz, C H Tator, D W Rowed, S R Reid, K Meguro, D F Andrews
雑誌名: Can J Neurol Sci. 1984 Nov;11(4):434-40.
Abstract/Text Fifty-nine patients were treated in a prospective, randomized comparison of pentobarbital and mannitol for the control of intracranial hypertension resulting from head injury. Patients with elevated intracranial pressure (ICP) after evacuation of intracranial hematomas were randomized to one of two treatment groups; mannitol initially or pentobarbital initially, followed by the second drug as required by further elevation of ICP. Similarly, patients with raised ICP but without hematomas requiring evacuation were randomly assigned to two treatment groups in an identical paradigm. Those with ICP elevation and no hematoma treated with pentobarbital as initial therapy had a 77% mortality compared to a 41% mortality for those with mannitol as initial treatment. Patients with evacuated hematomas had mortalities of 40% and 43% (no significant difference) for pentobarbital and mannitol respectively. In both no-hematoma and hematoma streams pentobarbital was less effective than mannitol for control of raised ICP. Multivariable statistical analysis indicates that pentobarbital coma is not better than mannitol for the treatment of intracranial hypertension and may be harmful in no-hematoma patients with intracranial hypertension after head injury.

PMID 6440704  Can J Neurol Sci. 1984 Nov;11(4):434-40.
著者: J D Ward, D P Becker, J D Miller, S C Choi, A Marmarou, C Wood, P G Newlon, R Keenan
雑誌名: J Neurosurg. 1985 Mar;62(3):383-8. doi: 10.3171/jns.1985.62.3.0383.
Abstract/Text In certain subgroups of severely head-injured patients, the mortality rate remains unacceptably high. The authors describe a randomized, controlled trial of prophylactic pentobarbital therapy in a group of these patients. Pentobarbital was started as soon as possible after the head injury, regardless of the intracranial pressure (ICP), and was continued for a prescribed period of time. The study included 53 consecutive head-injured patients over the age of 12 years, who had either an acute intradural hematoma (subdural and/or intracerebral, large enough to warrant surgical decompression), or no mass lesion but whose best motor response was abnormal flexion or extension. All patients in the study were randomly assigned to a control group (26 cases) or a pentobarbital-treated group (27 cases) once the diagnosis had been made and informed consent obtained. All patients were treated with the same protocol of aggressive resuscitation, prompt diagnosis and treatment of mass lesions, and intensive care, with close follow-up monitoring. The randomization was effective in producing a close match between the control and treated groups with respect to age, sex distribution, cause of injury, neurological status, intracranial lesions, prevalence of early systemic insults, midline shift, and initial ICP. Outcome was essentially the same in each group. There was no difference between groups in the incidence of elevated ICP, the duration of ICP elevation, or the response of ICP elevations to treatment. Arterial hypotension occurred in 14 patients (54%) in the treated group and only two patients (7%) in the untreated group. Based on these data the authors cannot recommend the prophylactic use of pentobarbital coma in the treatment of patients with severe head injury. They also believe that its use is accompanied by significant side effects which can potentially worsen the condition of a patient with severe head injury.

PMID 3882899  J Neurosurg. 1985 Mar;62(3):383-8. doi: 10.3171/jns.198・・・
著者: D F Kelly, D B Goodale, J Williams, D L Herr, E T Chappell, M J Rosner, J Jacobson, M L Levy, M A Croce, A H Maniker, G J Fulda, J V Lovett, O Mohan, R K Narayan
雑誌名: J Neurosurg. 1999 Jun;90(6):1042-52. doi: 10.3171/jns.1999.90.6.1042.
Abstract/Text OBJECT: Sedation regimens for head-injured patients are quite variable. The short-acting sedative-anesthetic agent propofol is being increasingly used in such patients, yet little is known regarding its safety and efficacy. In this multicenter double-blind trial, a titratable infusion of 2% propofol accompanied by low-dose morphine for analgesia was compared with a regimen of morphine sulfate in intubated head-injured patients. In both groups, other standard measures of controlling intracranial pressure (ICP) were also used.
METHODS: Forty-two patients from 11 centers were evaluated to assess both the safety and efficacy of propofol: 23 patients in the propofol group (mean time of propofol usage 95+/-87 hours) and 19 patients in the morphine group (mean time of morphine usage 70+/-54 hours). There was a higher incidence of poor prognostic indicators in the propofol group than in the morphine group: patient age older than 55 years (30.4% compared with 10.5%, p < 0.05), initial Glasgow Coma Scale scores of 3 to 5 (39.1% compared with 15.8%, p < 0.05), compressed or absent cisterns on initial computerized tomography scanning (78.3% compared with 57.9%, p < 0.05), early hypotension and/or hypoxia (26.1% compared with 10.5%, p = 0.07). During treatment there was a trend toward greater use of vasopressors in the propofol group. However, the mean daily ICP and cerebral perfusion pressure were generally similar between groups and, on therapy Day 3, ICP was lower in the propofol group compared with the morphine group (p < 0.05). Additionally, there was less use of neuromuscular blocking agents, benzodiazepines, pentobarbital, and cerebrospinal fluid drainage in the propofol group (p < 0.05). At 6 months postinjury, a favorable outcome (good recovery or moderate disability) was observed in 52.1% of patients receiving propofol and in 47.4% receiving morphine; the mortality rates were 17.4% and 21.1%, respectively. Patients who received the highest doses of propofol for the longest duration tended to have the best outcomes. There were no significant differences between groups in terms of adverse events.
CONCLUSIONS: Despite a higher incidence of poor prognostic indicators in the propofol group, ICP therapy was less intensive, ICP was lower on therapy Day 3, and long-term outcome was similar to that of the morphine group. These results suggest that a propofol-based sedation and an ICP control regimen is a safe, acceptable, and, possibly, desirable alternative to an opiate-based sedation regimen in intubated head-injured patients.

PMID 10350250  J Neurosurg. 1999 Jun;90(6):1042-52. doi: 10.3171/jns.1・・・
著者: Helen Ouyang, James Quinn
雑誌名: Emerg Med Clin North Am. 2010 Aug;28(3):471-85. doi: 10.1016/j.emc.2010.03.007.
Abstract/Text With a careful history, physical examination, and directed investigation, physicians can determine the likely cause of syncope in more than 50% and perhaps up to 80% of patients. Understanding the cause of syncope allows clinicians to determine the disposition of high- and low-risk patients. Patients with a potential malignant cause, such as a cardiac or neurologic condition, should be treated and admitted. Those with benign causes can be safely discharged. This article reviews the diagnosis and ED work-up of syncope, the different classifications of syncope, and prognosis. The use of specific decision rules in risk stratification and syncope in the pediatric population are discussed in another article.

Copyright 2010 Elsevier Inc. All rights reserved.
PMID 20709239  Emerg Med Clin North Am. 2010 Aug;28(3):471-85. doi: 10・・・
著者: Cherisse Berry, Eric J Ley, Marko Bukur, Darren Malinoski, Daniel R Margulies, James Mirocha, Ali Salim
雑誌名: Injury. 2012 Nov;43(11):1833-7. doi: 10.1016/j.injury.2011.08.014. Epub 2011 Sep 21.
Abstract/Text BACKGROUND: Systemic hypotension is a well documented predictor of increased mortality following traumatic brain injury (TBI). Hypotension is traditionally defined as systolic blood pressure (SBP)<90 mmHg. Recent evidence defines hypotension by a higher SBP in injured (non-TBI) trauma patients. We hypothesize that hypotension threshold requires a higher SBP in isolated moderate to severe TBI.
PATIENTS AND METHODS: A retrospective database review of all adults (≥ 15 years) with isolated moderate to severe TBI (head abbreviated injury score (AIS)≥ 3, all other AIS ≤ 3), admitted from five Level I and eight Level II trauma centres (Los Angeles County), between 1998 and 2005. Several fit statistic analyses were performed for each admission SBP from 60 to 180 mmHg to identify the model that most accurately defined hypotension for three age groups: 15-49 years, 50-69 years, and ≥ 70 years. The main outcome variable was mortality, and the optimal definition of hypotension for each group was determined from the best fit model. Adjusted odds ratios (AOR) were then calculated to determine increased odds in mortality for the defined optimal SBP within each age group.
RESULTS: A total of 15,733 patients were analysed. The optimal threshold of hypotension according to the best fit model was SBP of 110 mmHg for patients 15-49 years (AOR 1.98, CI 1.65-2.39, p<0.0001), 100 mmHg for patients 50-69 years (AOR 2.20, CI 1.46-3.31, p=0.0002), and 110 mmHg for patients ≥ 70 years (AOR 1.92, CI 1.35-2.74, p=0.0003).
CONCLUSIONS: Patients with isolated moderate to severe TBI should be considered hypotensive for SBP<110 mmHg. Further research should confirm this new definition of hypotension by correlation with indices of perfusion.

Copyright © 2011 Elsevier Ltd. All rights reserved.
PMID 21939970  Injury. 2012 Nov;43(11):1833-7. doi: 10.1016/j.injury.2・・・
著者: Megan Brenner, Deborah M Stein, Peter F Hu, Bizhan Aarabi, Kevin Sheth, Thomas M Scalea
雑誌名: J Trauma Acute Care Surg. 2012 May;72(5):1135-9. doi: 10.1097/TA.0b013e31824af90b.
Abstract/Text BACKGROUND: Vital signs, particularly blood pressure, are often manipulated to maximize perfusion and optimize recovery from severe traumatic brain injury (sTBI). We investigated the utility of automated continuously recorded vital signs to predict outcomes after sTBI.
METHODS: Sixty patients with head Abbreviated Injury Scale score ≥ 3, age >14 years, "isolated" TBI, and need for intracranial pressure monitoring were prospectively enrolled at a single, large urban tertiary care facility. Outcome was measured by mortality and extended Glasgow Outcome Scale (GOSE) at 12 months. Continuous, automated, digital data were collected every 6 seconds for 72 hours after admission, and 5-minute means of systolic blood pressure (SBP) were recorded. We calculated SBP as pressure × time dose (PTD) to describe the cumulative amplitude and duration of episodes above and below clinical thresholds. The extent and duration of the insults were calculated as percent time (%time), PTD, and PTD per day (PTD/D) of defined thresholds (SBP: <90 mm Hg, <100 mm Hg, <110 mm Hg, and <120 mm Hg; mean arterial pressure: <60 mm Hg and <70 mm Hg; heart rate: >100 bpm and >120 bpm; and SpO(2): <88% and <92%) for the first 12 hours, 24 hours, and 48 hours of intensive care unit admission. We analyzed their ability to predict mortality and GOSE by receiver operator characteristics.
RESULTS: Mean age was 33.9 (range, 16-83) years, mean admission Glasgow Coma Scale score 6.4 ± 3, and mean head Abbreviated Injury Scale score 4.2 ± 0.72. The 30-day mortality rate was 13.3%. Of the 45 patients in whom GOSE at 12 months was available, 28 (62%) had good neurologic outcomes (GOSE score >4). Traditional markers of poor outcome (admission SBP, admission Glasgow Coma Scale, and Marshall score) were not different between groups with good or poor outcome. PTD, PTD/D, and %time SBP <110 mm Hg and SBP <120 mm Hg predicted mortality at 12 hours, 24 hours, and 48 hours (p < 0.04). Percent time SBP <110 mm Hg in the first 24 hours was predictive of 12-month GOSE (p = 0.02). PTD/D SBP <120 mm Hg in the first 24 hours and PTD and PTD/D in the first 48 hours were also predictive of 12-month GOSE (p < 0.05).
CONCLUSIONS: Within the first 48 hours of intensive care unit admission, hypotension was found to be predictive of mortality and functional outcomes at higher thresholds than traditionally defined. Systemic blood pressure targets closer to 120 mm Hg may be more efficacious in minimizing secondary insults and particularly useful in settings without invasive intracranial monitoring capabilities.
LEVEL OF EVIDENCE: III, prognostic study.

PMID 22673237  J Trauma Acute Care Surg. 2012 May;72(5):1135-9. doi: 1・・・
著者: E Sorrentino, J Diedler, M Kasprowicz, K P Budohoski, C Haubrich, P Smielewski, J G Outtrim, A Manktelow, P J Hutchinson, J D Pickard, D K Menon, M Czosnyka
雑誌名: Neurocrit Care. 2012 Apr;16(2):258-66. doi: 10.1007/s12028-011-9630-8.
Abstract/Text INTRODUCTION: Pressure-reactivity index (PRx) is a useful tool in brain monitoring of trauma patients, but the question remains about its critical values. Using our TBI database, we identified the thresholds for PRx and other monitored parameters that maximize the statistical difference between death/survival and favorable/unfavorable outcomes. We also investigated how these thresholds depend on clinical factors such as age, gender and initial GCS.
METHODS: A total of 459 patients from our database were eligible. Tables of 2 × 2 format were created grouping patients according to survival/death or favorable/unfavorable outcomes and varying thresholds for PRx, ICP and CPP. Pearson's chi square was calculated, and the thresholds returning the highest score were assumed to have the best discriminative value. The same procedure was repeated after division according to clinical factors.
RESULTS: In all patients, we found that PRx had different thresholds for survival (0.25) and for favorable outcome (0.05). Thresholds of 70 mmHg for CPP and 22 mmHg for ICP were identified for both survival and favorable outcomes. The ICP threshold for favorable outcome was lower (18 mmHg) in females and patients older than 55 years. In logistic regression models, independent variables associating with mortality and unfavorable outcome were age, GCS, ICP and PRx.
CONCLUSION: The prognostic role of PRx is confirmed but with a lower threshold of 0.05 for favorable outcome than for survival (0.25). Results for ICP are in line with current guidelines. However, the lower value in elderly and in females suggests increased vulnerability to intracranial hypertension in these groups.

PMID 21964774  Neurocrit Care. 2012 Apr;16(2):258-66. doi: 10.1007/s12・・・
著者: Aleksandar Kostić, Ivan Stefanović, Vesna Novak, Dragan Veselinović, Goran Ivanov, Aleksandar Veselinović
雑誌名: Med Pregl. 2011 Sep-Oct;64(9-10):461-5.
Abstract/Text Since without prospective randomized studies it is not possible to have a clear attitude towards the importance of intracranial pressure monitoring, this study was aimed at examining the prognostic effect of the intracranial pressure monitoring and intracranial pressure oriented therapy in severe brain trauma patients, and at defining optimal intracranial pressure values for starting the treatment. Two groups of patients were treated in the study, one consisted of 32 patients undergoing intracranial pressure monitoring and the second group of 29 patients without intracranial pressure monitoring in the control group. The study was prospective with groups randomized. There were 53% survivals in the intracranial pressure monitored patients and 34% in the control group, with no significant difference in the survival rate between the two groups (chi2=2.11; p=0.15; p>0.05). The average intracranial pressure in the patients with intracranial hypertension who died was 27 mm Hg, while in the patients who survived the average intracranial pressure was significantly lower (Student's t test: t=2.91; p=0.008; p<0.01) and it was 18 mm Hg. We recommend starting intracranial pressure oriented therapy when the patient's intracranial pressure exceeds 18 mmHg during 2 hours of monitoring.

PMID 22097111  Med Pregl. 2011 Sep-Oct;64(9-10):461-5.
著者: Jinn-Rung Kuo, Tsong-Chih Yeh, Kuan-Chin Sung, Che-Chuan Wang, Chi-Wen Chen, Chung-Ching Chio
雑誌名: J Clin Neurosci. 2006 Feb;13(2):218-23. doi: 10.1016/j.jocn.2005.01.012. Epub 2006 Feb 3.
Abstract/Text From December 2002 to January 2004, 30 patients (20 men and 10 women; mean age 36.8 years [+/- 14.9 years]) with preoperative Glasgow Coma Scale scores of 8 or less underwent emergency haematoma evacuation surgery and continuous intracranial pressure (ICP), cerebral perfusion pressure (CPP) and mean arterial blood pressure monitoring to determine ICP and CPP thresholds to predict patient outcomes. Receiver-operating characteristic (ROC) curves were plotted. Using the ROC curve, the diagnostic accuracy is given by the area under the curve and at the point on the curve farthest from the diagonal, which indicates the threshold value. The results showed that the initial ICP for unfavourable outcomes was 47.4 +/- 21.4 mmHg, resulting in a CPP of 22.8 +/- 12.83 mmHg. The initial ICP for favourable outcomes was 26.4 +/- 10.1 mmHg, resulting in a CPP of 48.8 +/- 13.4 mmHg. The CPP had the largest area under the ROC curve in all stages of the operation, corresponding to intraoperative CPP thresholds of 37 mmHg (initial), 51.8 mmHg (intraoperative) and 52 mmHg (after scalp closure). The ROC curve analysis showed that CPP was a better predictor of outcome than ICP.

PMID 16459087  J Clin Neurosci. 2006 Feb;13(2):218-23. doi: 10.1016/j.・・・
著者: Baxter B Allen, Ya-Lin Chiu, Linda M Gerber, Jamshid Ghajar, Jeffrey P Greenfield
雑誌名: Pediatr Crit Care Med. 2014 Jan;15(1):62-70. doi: 10.1097/PCC.0b013e3182a556ea.
Abstract/Text OBJECTIVES: Evidence-based traumatic brain injury guidelines support cerebral perfusion pressure thresholds for adults at a class 2 level, but evidence is lacking in younger patients. The purpose of this study is to identify the impact of age-specific cerebral perfusion pressure thresholds on short-term survival among patients with severe traumatic brain injury.
DESIGN: Institutional review board-approved, prospective, observational cohort study.
SETTING: Level I or II trauma centers in New York State.
PATIENTS: Data on all patients with a postresuscitation Glasgow Coma Score less than 9 were added in the Brain Trauma Foundation prospective New York State TBI-trac database.
MEASUREMENTS AND MAIN RESULTS: We calculated the survival rates and relative risks of mortality for patients with severe traumatic brain injury based on predefined age-specific cerebral perfusion pressure thresholds. A higher threshold and a lower threshold were defined for each age group: 60 and 50 mm Hg for 12 years old or older, 50 and 35 mm Hg for 6-11 years, and 40 and 30 mm Hg for 0-5 years. Patients were stratified into age groups of 0-11, 12-17, and 18 years old or older. Three exclusive groups of CPP-L (events below low cerebral perfusion pressure threshold), CPP-B (events between high and low cerebral perfusion pressure thresholds), and CPP-H (events above high cerebral perfusion pressure threshold) were defined. As an internal control, we evaluated the associations between cerebral perfusion pressure events and events of hypotension and elevated intracranial pressure. Survival was significantly higher in 0-11 and 18 years old or older age groups for patients with CPP-H events compared with those with CPP-L events. There was a significant decrease in survival with prolonged exposure to CPP-B events for the 0-11 and 18 years old and older age groups when compared with the patients with CPP-H events (p = 0.0001 and p = 0.042, respectively). There was also a significant decrease in survival with prolonged exposure to CPP-L events in all age groups compared with the patients with CPP-H events (p< 0.0001 for 0- to 11-yr olds, p = 0.0240 for 12- to 17-yr olds, and p < 0.0001 for 18-yr old and older age groups). The 12- to 17-year olds had a significantly higher likelihood of survival compared with adults with prolonged exposure to CPP-L events (< 50 mm Hg). CPP-L events were significantly related to systemic hypotension for the 12- to 17-year-old group (p = 0.004) and the 18-year-old and older group (p < 0.0001). CPP-B events were significantly related to systemic hypotension in the 0- to 11-year-old group (p = 0.014). CPP-B and CPP-L events were significantly related to elevated intracranial pressure in all age groups.
CONCLUSIONS: Our data provide new evidence that cerebral perfusion pressure targets should be age specific. Furthermore, cerebral perfusion pressure goals above 50 or 60 mm Hg in adults, above 50 mm Hg in 6- to 17-year olds, and above 40 mm Hg in 0- to 5-year olds seem to be appropriate targets for treatment-based studies. Systemic hypotension had an inconsistent relationship to events of low cerebral perfusion pressure, whereas elevated intracranial pressure was significantly related to all low cerebral perfusion pressure events across all age groups. This may impart a clinically important difference in care, highlighting the necessity of controlling intracranial pressure at all times, while targeting systolic blood pressure in specific instances.

PMID 24196011  Pediatr Crit Care Med. 2014 Jan;15(1):62-70. doi: 10.10・・・
著者: Jason J J Chang, Teddy S Youn, Dan Benson, Heather Mattick, Nicholas Andrade, Caryn R Harper, Carol B Moore, Christopher J Madden, Ramon R Diaz-Arrastia
雑誌名: Crit Care Med. 2009 Jan;37(1):283-90. doi: 10.1097/CCM.0b013e318192fbd7.
Abstract/Text OBJECTIVE: Assess the prevalence of brain tissue hypoxia in patients with severe traumatic brain injuries (TBI), and to characterize the relationship between brain tissue hypoxia and functional outcome.
DESIGN: Retrospective review of severe TBI patients.
SETTING: Intensive care unit of a level I trauma center.
PATIENTS: Twenty-seven patients with severe TBI requiring intracranial pressure (ICP) monitoring. Median age was 22 yrs, and a majority (63%) had traumatic subarachnoid hemorrhage.
INTERVENTIONS: Hourly assessments of ICP, brain tissue oxygen, mean arterial pressure, fraction of inspired oxygen (FiO2), partial pressure of arterial carbon dioxide (PaCO2), and hemoglobin concentration (hemoglobin) were recorded. Outcome was assessed 6-9 months postinjury.
MEASUREMENTS AND MAIN RESULTS: Mean (SD) ICP and BTpO2 were 13.7 (6.6) cm H2O and 30.8 (13.6) mm Hg. A total of 13.5% (379) of the BTpO2 values recorded were < 20 mm Hg, only 86 of which were associated with ICP > or = 20 cm H2O. This prevalence was comparable with episodes of ICP elevations above 20 cm H2O (14.1%, 397). Hypoxic episodes were more common when cerebral perfusion pressure was below 60 mm Hg (relative risk = 3.0, p < 0.0001). We did not find an association in hypoxic risk and hemoglobin in the range of 7-12 g/dL or PaCO2 in the range of 25-40 mm Hg. Subjects with hourly episodes (epochs) of hypoxia > 20% of the time had poorer scores on outcome measures compared with those with fewer hypoxic epochs.
CONCLUSIONS: Hypoxic episodes are common after severe TBI, and most are independent of ICP elevations. Most episodes of hypoxia occur while cerebral perfusion pressure and mean arterial pressure are within the accepted target range. There is no clear association between PaCO2 and hemoglobin with BTpO2. The young age and high prevalence of traumatic subarachnoid hemorrhage in this cohort may limit its generalizability. Increased frequency of hypoxic episodes is associated with poor functional outcome.

PMID 19050612  Crit Care Med. 2009 Jan;37(1):283-90. doi: 10.1097/CCM.・・・
著者: Ulf Johnson, Pelle Nilsson, Elisabeth Ronne-Engström, Tim Howells, Per Enblad
雑誌名: Neurosurgery. 2011 Mar;68(3):714-21; discussion 721-2. doi: 10.1227/NEU.0b013e3182077313.
Abstract/Text BACKGROUND: Cerebral pressure autoregulation (CPA) is defined as the ability of the brain vasculature to maintain a constant blood flow over a range of different systemic blood pressures by means of contraction and dilatation.
OBJECTIVE: To study CPA in relation to physiological parameters, treatment, and outcome in a series of traumatic brain injury patients.
METHODS: In this prospective observational study, 44 male and 14 female patients (age, 15-72 years; mean, 38.7 years; Glasgow Coma Scale score, 4-13; median, 7) were analyzed. Patients were divided into groups on the basis of status of CPA (more pressure active vs more pressure passive) and level of cerebral perfusion pressure (CPP; low vs high CPP). The proportions of favorable outcome in the groups were assessed. Differences in physiological variables in the different groups were analyzed.
RESULTS: Patients with more impaired CPA treated at CPP levels below median had a significantly higher proportion of favorable outcome compared with patients with more impaired CPA treated at CPP levels above median. No significant difference in outcome was seen between patients with more intact CPA when divided by level of CPP. In patients with more impaired CPA, CPP<50 mm Hg and CPP<60 mm Hg were associated with favorable outcome, whereas CPP>70 mm Hg and CPP>80 mm Hg were associated with unfavorable outcome. In patients with more intact CPA, no difference in physiological variables was seen between patients with favorable and unfavorable outcomes.
CONCLUSION: Our results support that in traumatic brain injury patients with impaired CPA, CPP should not be elevated.

PMID 21311298  Neurosurgery. 2011 Mar;68(3):714-21; discussion 721-2. ・・・
著者: J W Lin, J T Tsai, C M Lin, L M Lee, K S Hung, S J Huang, S H Hsiao, W Y Chung, M D Tsai, C C Hsia, C C Hung, W T Chiu
雑誌名: Acta Neurochir Suppl. 2008;101:131-6.
Abstract/Text Traumatic brain injury (TBI) is a major cause of death and disability. In the 2000 guidelines, one of the suggestions for TBI treatment was to maintain cerebral perfusion pressure (CPP) < or = 70 mmHg. But in the 2003 guidelines, the suggestion was changed to < or = 60 mmHg. There have been some discrepancies of opinions about this recommendation in recent publications. In this study, we retrospectively reviewed 305 severe TBI (STBI) patients with Glasgow Coma Scales (GCS) < or = 8 between January 1, 2002 and March 31, 2003. The study group was stratified according to use or nonuse of intracranial pressure (ICP) monitoring, ICP levels, ages, and GCS levels in order to test the correlation between CCP and the prognosis. The patients < 50-year-old, with higher GCS level, with ICP monitoring, and with ICP levels < 20 mmHg had lower mortality rates and better prognosis (GOS) (p < 0.05 or 0.001). The patients in the GCS 3-5 subgroup had a significantly lower mortality and better prognosis if the CPP value was maintained higher than 70 mmHg (p < 0.05) The optimal CPP maintained < or = 60 mmHg did not fit in all STBI patients. Our study concludes that it is critical to maintain CPP substantially higher in lower GCS level patients.

PMID 18642647  Acta Neurochir Suppl. 2008;101:131-6.
著者: Evert A Eriksson, Jeffrey F Barletta, Bryan E Figueroa, Bruce W Bonnell, Chris A Sloffer, Wayne E Vanderkolk, Karen J McAllen, Mickey Ott
雑誌名: J Trauma Acute Care Surg. 2012 May;72(5):1345-9. doi: 10.1097/TA.0b013e318249a0f4.
Abstract/Text BACKGROUND: Utilization of brain tissue oxygenation (pBtO(2)) is an important but controversial variable in the treatment of traumatic brain injury. We hypothesize that pBtO(2) values over the first 72 hours of monitoring are predictive of mortality.
METHODS: Consecutive, adult patients with severe traumatic brain injury and pBtO(2) monitors were retrospectively identified. Time-indexed measurements of pBtO(2), cerebral perfusion pressure (CPP), and intracranial pressure (ICP) were collected, and average values over 4-hour blocks were determined. Patients were stratified according to survival, and repeated measures analysis of variance was used to compare pBtO(2), CPP, and ICP. The pBtO(2) threshold most predictive for survival was determined.
RESULTS: There were 8,759 time-indexed data points in 32 patients. The mean age was 39 years ± 16.5 years, injury severity score was 27.7 ± 10.7, and Glasgow Coma Scale score was 6.6 ± 3.4. Survival was 68%. Survivors consistently demonstrated higher pBtO(2) values compared with nonsurvivors including age as a covariate (F = 12.898, p < 0.001). Individual pBtO(2) was higher at the time points 8 hours, 12 hours, 20 hours to 44 hours, 52 hours to 60 hours, and 72 hours of monitoring (p < 0.05). There was no difference in ICP (F = 1.690, p = 0.204) and CPP (F = 0.764, p = 0.389) values between survivors and nonsurvivors including age as a covariate. Classification and regression tree analysis identified 29 mm Hg as the threshold at which pBtO(2) was most predictive for mortality.
CONCLUSION: The first 72 hours of pBtO(2) neurologic monitoring predicts mortality. When the pBtO(2) monitor remains below 29 mm Hg in the first 72 hours of monitoring, mortality is increased. This study challenges the brain oxygenation threshold of 20 mm Hg that has been used conventionally and delineates a time for monitoring pBtO(2) that is predictive of outcome.
LEVEL OF EVIDENCE: III, prognostic study.

PMID 22673264  J Trauma Acute Care Surg. 2012 May;72(5):1345-9. doi: 1・・・
著者: Arturo Chieregato, Maurizia Marchi, Enrico Fainardi, Luigi Targa
雑誌名: J Neurosurg Anesthesiol. 2007 Oct;19(4):222-8. doi: 10.1097/ANA.0b013e31806589f6.
Abstract/Text Arterio-venous pCO2 difference (AVDpCO2) and estimated respiratory quotient, the ratio between AVDpCO2 and arterio-venous O2 difference, may be potentially useful estimators of irreversible posttraumatic global cerebral ischemia. Our aim was to evaluate their relevance, along with arterio-venous lactate difference (AVDL) and lactate oxygen index (LOI), in early outcome prediction. The retrospective study involved 55 patients with severe head injury, admitted consecutively in a multidisciplinary intensive care unit of a general hospital. A retrograde jugular catheter was placed as soon as possible, allowing for 324 simultaneous arterio-jugular samples to be taken throughout the first 48-hour postinjury. Early brain death (within 48 h) was assumed to be due to early global ischemia. A multivariate model including clinical and radiologic descriptors and jugular bulb variables showed that a widening of AVDL and LOI was associated with early brain death. Whereas in the patients who died, a progressive worsening of AVDpCO2 and estimated respiratory quotient, associated with corresponding changes in AVDL and LOI were observed, in patients who survived the widening of AVDpCO2 normalized along with that of arterio-venous O2 difference. These findings suggest that the isolated measurement of widening AVDpCO2 is not specific for global cerebral ischemia, but its observation over time could be potentially more useful.

PMID 17893572  J Neurosurg Anesthesiol. 2007 Oct;19(4):222-8. doi: 10.・・・
著者: R M Chesnut, L F Marshall, M R Klauber, B A Blunt, N Baldwin, H M Eisenberg, J A Jane, A Marmarou, M A Foulkes
雑誌名: J Trauma. 1993 Feb;34(2):216-22.
Abstract/Text As triage and resuscitation protocols evolve, it is critical to determine the major extracranial variables influencing outcome in the setting of severe head injury. We prospectively studied the outcome from severe head injury (GCS score < or = 8) in 717 cases in the Traumatic Coma Data Bank. We investigated the impact on outcome of hypotension (SBP < 90 mm Hg) and hypoxia (Pao2 < or = 60 mm Hg or apnea or cyanosis in the field) as secondary brain insults, occurring from injury through resuscitation. Hypoxia and hypotension were independently associated with significant increases in morbidity and mortality from severe head injury. Hypotension was profoundly detrimental, occurring in 34.6% of these patients and associated with a 150% increase in mortality. The increased morbidity and mortality related to severe trauma to an extracranial organ system appeared primarily attributable to associated hypotension. Improvements in trauma care delivery over the past decade have not markedly altered the adverse influence of hypotension. Hypoxia and hypotension are common and detrimental secondary brain insults. Hypotension, particularly, is a major determinant of outcome from severe head injury. Resuscitation protocols for brain injured patients should assiduously avoid hypovolemic shock on an absolute basis.

PMID 8459458  J Trauma. 1993 Feb;34(2):216-22.
著者: Eric J Ley, Matthew B Singer, Morgan A Clond, Alexandra Gangi, Jim Mirocha, Marko Bukur, Carlos V Brown, Ali Salim
雑誌名: J Trauma. 2011 Dec;71(6):1689-93. doi: 10.1097/TA.0b013e31823cc5df.
Abstract/Text BACKGROUND: Although avoiding hypotension is a primary focus after trauma, elevated systolic blood pressure (SBP) is frequently disregarded. The purpose of this study was to determine the association between elevated admission SBP and delayed outcomes after trauma.
METHODS: The Los Angeles County Trauma System Database was queried for all patients between 2003 and 2008 with blunt injuries who survived for at least 2 days after admission. Demographics and outcomes (pneumonia and mortality) were compared at various admission SBP subgroups (≥160 mm Hg, ≥170 mm Hg, ≥180 mm Hg, ≥190 mm Hg, ≥200 mm Hg, ≥210 mm Hg, and ≥220 mm Hg). Patients with moderate-to-severe traumatic brain injury (TBI), defined as head Abbreviated Injury Score ≥3, were then identified and compared with those without using multivariable logistic regression.
RESULTS: Data accessed from 14,382 blunt trauma admissions identified 2,601 patients with moderate-to-severe TBI (TBI group) and 11,781 without moderate-to-severe TBI (non-TBI group) who were hospitalized ≥2 days. Overall mortality was 2.9%, 7.1% for TBI patients, and 1.9% for non-TBI patients. Overall pneumonia was 4.6%, 9.5% for TBI patients, and 3.6% for non-TBI patients. Regression modeling determined SBP ≥160 mm Hg was a significant predictor of mortality in TBI patients (adjusted odds ratio [AOR], 1.59; confidence interval [CI], 1.10-2.29; p = 0.03) and non-TBI patients (AOR, 1.47; CI, 1.14-1.90; p = 0.003). Similarly, SBP ≥160 mm Hg was a significant predictor for increased pneumonia in TBI patients (AOR, 1.79; CI, 1.30-2.46; p = 0.0004), compared with non-TBI patients (AOR, 1.28; CI, 0.97-1.69; p = 0.08).
CONCLUSIONS: In blunt trauma patients with or without TBI, elevated admission SBP was associated with worse delayed outcomes. Prospective research is necessary to determine whether algorithms that manage elevated blood pressure after trauma, especially after TBI, affect mortality or pneumonia.

PMID 22182876  J Trauma. 2011 Dec;71(6):1689-93. doi: 10.1097/TA.0b013・・・
著者: Halinder S Mangat, Ya-Lin Chiu, Linda M Gerber, Marjan Alimi, Jamshid Ghajar, Roger Härtl
雑誌名: J Neurosurg. 2015 Jan;122(1):202-10. doi: 10.3171/2014.10.JNS132545.
Abstract/Text OBJECT: Increased intracranial pressure (ICP) in patients with traumatic brain injury (TBI) is associated with a higher mortality rate and poor outcome. Mannitol and hypertonic saline (HTS) have both been used to treat high ICP, but it is unclear which one is more effective. Here, the authors compare the effect of mannitol versus HTS on lowering the cumulative and daily ICP burdens after severe TBI.
METHODS: The Brain Trauma Foundation TBI-trac New York State database was used for this retrospective study. Patients with severe TBI and intracranial hypertension who received only 1 type of hyperosmotic agent, mannitol or HTS, were included. Patients in the 2 groups were individually matched for Glasgow Coma Scale score (GCS), pupillary reactivity, craniotomy, occurrence of hypotension on Day 1, and the day of ICP monitor insertion. Patients with missing or erroneous data were excluded. Cumulative and daily ICP burdens were used as primary outcome measures. The cumulative ICP burden was defined as the total number of days with an ICP of > 25 mm Hg, expressed as a percentage of the total number of days of ICP monitoring. The daily ICP burden was calculated as the mean daily duration of an ICP of > 25 mm Hg, expressed as the number of hours per day. The numbers of intensive care unit (ICU) days, numbers of days with ICP monitoring, and 2-week mortality rates were also compared between the groups. A 2-sample t-test or chi-square test was used to compare independent samples. The Wilcoxon signed-rank or Cochran-Mantel-Haenszel test was used for comparing matched samples.
RESULTS: A total of 35 patients who received only HTS and 477 who received only mannitol after severe TBI were identified. Eight patients in the HTS group were excluded because of erroneous or missing data, and 2 other patients did not have matches in the mannitol group. The remaining 25 patients were matched 1:1. Twenty-four patients received 3% HTS, and 1 received 23.4% HTS as bolus therapy. All 25 patients in the mannitol group received 20% mannitol. The mean cumulative ICP burden (15.52% [HTS] vs 36.5% [mannitol]; p = 0.003) and the mean (± SD) daily ICP burden (0.3 ± 0.6 hours/day [HTS] vs 1.3 ± 1.3 hours/day [mannitol]; p = 0.001) were significantly lower in the HTS group. The mean (± SD) number of ICU days was significantly lower in the HTS group than in the mannitol group (8.5 ± 2.1 vs 9.8 ± 0.6, respectively; p = 0.004), whereas there was no difference in the numbers of days of ICP monitoring (p = 0.09). There were no significant differences between the cumulative median doses of HTS and mannitol (p = 0.19). The 2-week mortality rate was lower in the HTS group, but the difference was not statistically significant (p = 0.56).
CONCLUSIONS: HTS given as bolus therapy was more effective than mannitol in lowering the cumulative and daily ICP burdens after severe TBI. Patients in the HTS group had significantly lower number of ICU days. The 2-week mortality rates were not statistically different between the 2 groups.

PMID 25380107  J Neurosurg. 2015 Jan;122(1):202-10. doi: 10.3171/2014.・・・
著者: G L Clifton, S Allen, P Barrodale, P Plenger, J Berry, S Koch, J Fletcher, R L Hayes, S C Choi
雑誌名: J Neurotrauma. 1993 Fall;10(3):263-71; discussion 273.
Abstract/Text Forty-six patients with severe nonpenetrating brain injury [Glasgow Coma Scale (GCS) 4-7] were randomized to standard management at 37 degrees C (n = 22) and to standard management with systemic hypothermia to 32 to 33 degrees C (n = 24). The two groups were balanced in terms of age (Wilcoxon's rank sum test, p > 0.95), randomizing GCS (chi-square test, p = 0.54), and primary diagnosis. Cooling was begun within 6 h of injury by use of cooling blankets. Metocurine and morphine were given hourly during induction and maintenance of hypothermia. Rewarming was at a rate of 1 degree C per 4 h beginning 48 h after intravascular temperature had reached 33 degrees C. Muscle relaxants and sedation were continued until core temperature reached 35 degrees C. There were no cardiac or coagulopathy-related complications. Seizure incidence was lower in the hypothermia group (Fisher's exact text, p = 0.019). Sepsis was seen more commonly in the hypothermia group, but difference was not statistically significant (chi-square test). Mean Glasgow Outcome Scale (GOS) score at 3 months after injury showed an absolute increase of 16% (i.e., 36.4-52.2%) in the number of patients in the Good Recovery/Moderate Disability (GR/MD) category as compared with Severe Disability/Vegetative/Dead (SD/V/D) (chi-square test, p > 0.287). Based on evidence of improved neurologic outcome with minimal toxicity, we believe that phase III testing of moderate systemic hypothermia in patients with severe head injury is warranted.

PMID 8258839  J Neurotrauma. 1993 Fall;10(3):263-71; discussion 273.
著者: M Aibiki, S Maekawa, S Yokono
雑誌名: Crit Care Med. 2000 Dec;28(12):3902-6.
Abstract/Text OBJECTIVE: To examine the levels of thromboxane B2 (TXB2) and 6-keto prostaglandin F1alpha (6-keto PGF1alpha) production in arterial and internal jugular bulb sera in patients with traumatic brain injury (TBI). TBI is associated with arachidonate release and may be associated with an imbalance of vasoconstricting and vasodilating cyclooxygenase metabolites.
DESIGN: A prospective, randomized study.
SETTING: The intensive care unit of a medical university hospital.
INTERVENTIONS: Twenty-six ventilated TBI patents (Glasgow Coma Scale score on admission, < or = 8 points) were divided randomly into two groups: a hypothermic group (n = 15), in which the patients were cooled to 32 to 33 degrees C after being giving vecuronium, midazolam, and buprenorphine; and a normothermic group (n = 11), in which the patients' body temperature was controlled at 36 to 37 degrees C by surface cooling using the same treatment as the hypothermic group. Body temperature control including normothermia was started 3 to 4 hrs after injury. The duration of hypothermia usually lasted for 3 to 4 days, after which the patients were rewarmed at a rate of approximately 1 C per day.
MEASUREMENTS AND MAIN RESULTS: Blood sampling for TXB2 and 6-keto PGF1alpha was started shortly after admission in both groups. Arterial TXB2 levels on admission in both groups were elevated remarkably, but not 6-keto PGF1alpha, thereby causing an imbalance of the prostanoids after injury. In the normothermic group, TXB2 decreased transiently, but this prostanoid increased again 3 days after the injury. In the hypothermic group, such prostanoid differences disappeared shortly after therapy, and the condition was sustained for 10 days. Hypothermia attenuated differences in TXB2 levels between arterial and internal jugular bulb sera, which may reflect reduced cerebral prostanoid production. The Glasgow Outcome Scale score 6 months after the insult in the hypothermic group was significantly higher than that in the normothermic group (p = .04).
CONCLUSION: The current results from a limited number of patients suggest that moderate hypothermia may reduce prostanoid production after TBI, thereby attenuating an imbalance of thromboxane A2 and prostaglandin I2. However, it must be clarified whether the changes in the prostanoid after moderate hypothermia are a secondary effect of other mediator changes or whether they simply represent an epiphenomenon that is mechanistically unrelated to damage in TBI.

PMID 11153633  Crit Care Med. 2000 Dec;28(12):3902-6.
著者: J Jiang, M Yu, C Zhu
雑誌名: J Neurosurg. 2000 Oct;93(4):546-9. doi: 10.3171/jns.2000.93.4.0546.
Abstract/Text OBJECT: The goal of this study was to investigate the protective effects of long-term (3-14 days) mild hypothermia therapy (33-35 degrees C) on outcome in 87 patients with severe traumatic brain injury (TBI) (Glasgow Coma Scale score < or = 8).
METHODS: In 43 patients assigned to a mild hypothermia group, body temperatures were cooled to 33 to 35 degrees C a mean of 15 hours after injury and kept at 33 to 35 degrees C for 3 to 14 days. Rewarming commenced when the individual patient's intracranial pressure (ICP) returned to the normal level. Body temperatures in 44 patients assigned to a normothermia group were maintained at 37 to 38 degrees C. Each patient's outcome was evaluated 1 year later by using the Glasgow Outcome Scale. One year after TBI, the mortality rate was 25.58% (11 of 43 patients) and the rate of favorable outcome (good recovery or moderate disability) was 46.51% (20 of 43 patients) in the mild hypothermia group. In the normothermia group, the mortality rate was 45.45% (20 of 44 patients) and the rate of favorable outcome was 27.27% (12 of 44 patients) (p < 0.05). Induced mild hypothermia also markedly reduced ICP (p < 0.01) and inhibited hyperglycemia (p < 0.05). The rates of complication were not significantly different between the two groups.
CONCLUSIONS: The data produced by this study demonstrate that long-term mild hypothermia therapy significantly improves outcomes in patients with severe TBI.

PMID 11014530  J Neurosurg. 2000 Oct;93(4):546-9. doi: 10.3171/jns.200・・・
著者: Wu-si Qiu, Wei-guo Liu, Hong Shen, Wei-min Wang, Zhi-Liang Hang, Ying Zhang, Su-jun Jiang, Xiao-feng Yang
雑誌名: Chin J Traumatol. 2005 Feb;8(1):27-32.
Abstract/Text OBJECTIVE: To investigate the therapeutic effect of mild hypothermia on severe traumatic brain injury.
METHODS: Eighty-six in-patients with severe traumatic brain injury treated ordinarily were consecutively randomized into two groups: a hypothermia group (n=43) and a normothermia group (the control group, n=43). In the hypothermia group, the core temperature (i.e., nasopharyngeal or brain temperature) of the patient was reduced to and maintained at 33-35 degrees C with a systemic cooling blanket. Natural rewarming began after 3-5 days (mean: 4.3 days) of hypothermia treatment. In the control group, the patient received no hypothermia treatment. The vital sign, extradural pressure and serum superoxide dismutase were observed and measured during treatment, and the complications as well as the Glasgow outcome scale were evaluated at 2 years after injury.
RESULTS: The mean extradural pressure in the hypothermia group (27.38 mm Hg +/- 4.88 mm Hg at 24 hours, 29.40 mm Hg +/- 4.50 mm Hg at 48 hours and 26.40 mm Hg +/- 4.13 mm Hg at 72 hours after injury) was much lower than that in the control group (32.63 mm Hg +/- 3.00 mm Hg, 34.80 mm Hg +/- 6.00 mm Hg and 31.81 mm Hg +/- 4.50 mm Hg respectively at 24, 48 and 72 hours, P<0.05). The mean serum superoxide dismutase levels in the hypothermia group on days 3 and 7 (583.7 microg/L +/- 99.6 microg/L and 699.4 microg/L +/- 217.3 microg/L, respectively) were much higher than those in the control group at the same time period (446.6 microg/L +/- 79.5 microg/L and 497.1 microg/L +/- 101.2 microg/L, respectively, P<0.01). The recovery rates at 2 years after injury were 65.1% in the hypothermia group and 37.2% in the control group (P<0.05). The mortality rates were 25.6% in the hypothermia group and 51.2% in the control group (P<0.05). The complications, including pulmonary infections, thrombocytopenia (platelet count < 100 x 10(9)/L), hemorrhage in the digestive tract, electrolyte disorders and renal malfunction, were managed without severe sequelae.
CONCLUSIONS: Mild hypothermia is a safe and effective therapeutic method, which can lower the extradural pressure, increase the serum superoxide dismutase and improve the neurological outcomes without severe complications in the patients with severe traumatic brain injury.

PMID 15676086  Chin J Traumatol. 2005 Feb;8(1):27-32.
著者: Guy L Clifton, Alex Valadka, David Zygun, Christopher S Coffey, Pamala Drever, Sierra Fourwinds, L Scott Janis, Elizabeth Wilde, Pauline Taylor, Kathy Harshman, Adam Conley, Ava Puccio, Harvey S Levin, Stephen R McCauley, Richard D Bucholz, Kenneth R Smith, John H Schmidt, James N Scott, Howard Yonas, David O Okonkwo
雑誌名: Lancet Neurol. 2011 Feb;10(2):131-9. doi: 10.1016/S1474-4422(10)70300-8. Epub 2010 Dec 17.
Abstract/Text BACKGROUND: The inconsistent effect of hypothermia treatment on severe brain injury in previous trials might be because hypothermia was induced too late after injury. We aimed to assess whether very early induction of hypothermia improves outcome in patients with severe brain injury.
METHODS: The National Acute Brain Injury Study: Hypothermia II (NABIS: H II) was a randomised, multicentre clinical trial of patients with severe brain injury who were enrolled within 2·5 h of injury at six sites in the USA and Canada. Patients with non-penetrating brain injury who were 16-45 years old and were not responsive to instructions were randomly assigned (1:1) by a random number generator to hypothermia or normothermia. Patients randomly assigned to hypothermia were cooled to 35°C until their trauma assessment was completed. Patients who had none of a second set of exclusion criteria were either cooled to 33°C for 48 h and then gradually rewarmed or treated at normothermia, depending upon their initial treatment assignment. Investigators who assessed the outcome measures were masked to treatment allocation. The primary outcome was the Glasgow outcome scale score at 6 months. Analysis was by modified intention to treat. This trial is registered with ClinicalTrials.gov, NCT00178711.
FINDINGS: Enrolment occurred from December, 2005, to June, 2009, when the trial was terminated for futility. Follow-up was from June, 2006, to December, 2009. 232 patients were initially randomised a mean of 1·6 h (SD 0·5) after injury: 119 to hypothermia and 113 to normothermia. 97 patients (52 in the hypothermia group and 45 in the normothermia group) did not meet any of the second set of exclusion criteria. The mean time to 35°C for the 52 patients in the hypothermia group was 2·6 h (SD 1·2) and to 33°C was 4·4 h (1·5). Outcome was poor (severe disability, vegetative state, or death) in 31 of 52 patients in the hypothermia group and 25 of 56 in the normothermia group (relative risk [RR] 1·08, 95% CI 0·76-1·53; p=0·67). 12 patients in the hypothermia group died compared with eight in the normothermia group (RR 1·30, 95% CI 0·58-2·52; p=0·52).
INTERPRETATION: This trial did not confirm the utility of hypothermia as a primary neuroprotective strategy in patients with severe traumatic brain injury.

Copyright © 2011 Elsevier Ltd. All rights reserved.
PMID 21169065  Lancet Neurol. 2011 Feb;10(2):131-9. doi: 10.1016/S1474・・・
著者: Ji-Yao Jiang, Wei Xu, Wei-Ping Li, Guo-Yi Gao, Ying-Hui Bao, Yu-Min Liang, Qi-Zhong Luo
雑誌名: J Cereb Blood Flow Metab. 2006 Jun;26(6):771-6. doi: 10.1038/sj.jcbfm.9600253.
Abstract/Text To compare the effect of long-term mild hypothermia versus short-term mild hypothermia on the outcome of 215 severe traumatic brain injured patients with cerebral contusion and intracranial hypertension. At three medical centers, 215 patients aged 18 to 45 years old with an admission Glasgow Coma Scale < or =8 within 4 h after injury were randomly divided into two groups: long-term mild hypothermia group (n = 108) for 5+/-1.3 days mild hypothermia therapy and short-term mild hypothermia group (n = 107) for 2+/-0.6 days mild hypothermia therapy. All patients had intracranial hypertension and frontotemporoparietal contusion with midline shift >1 cm confirmed on computed tomographic scan. Glasgow Outcome Scale at 6-month follow-up, 47 cases had favorable outcome (43.5%), and other 61 cases had unfavorable outcome (56.5%) in the long-term mild hypothermia group. However, only 31 cases had favorable outcome (29.0%), and other 76 cases had unfavorable outcome (71.0%) in the short-term mild hypothermia group (P < 0.05). The intracranial pressure significantly rebounded after rewarming in the short-term mild hypothermia group, but not in the long-term mild hypothermia (P < 0.05). Furthermore, the incidence of stress ulcer, epilepsy, pulmonary infection, intracranial infection did not significantly differ between the two groups (P > 0.05). Compared with short-term mild hypothermia, long-term mild hypothermia significantly improves the outcome of severe traumatic brain injured patients with cerebral contusion and intracranial hypertension without significant complications. Our data suggest that 5 days of long-term cooling is more efficacious than 2 days of short-term cooling when mild hypothermia is used to control refractory intracranial hypertension in patients with severe traumatic brain injury.

PMID 16306933  J Cereb Blood Flow Metab. 2006 Jun;26(6):771-6. doi: 10・・・
著者: W G Liu, W S Qiu, Y Zhang, W M Wang, F Lu, X F Yang
雑誌名: J Int Med Res. 2006 Jan-Feb;34(1):58-64. doi: 10.1177/147323000603400107.
Abstract/Text We prospectively investigated non-invasive selective brain cooling (SBC) in patients with severe traumatic brain injury. Sixty-six in-patients were randomized into three groups. In one group, brain temperature was maintained at 33 - 35 degrees C by cooling the head and neck (SBC); in a second group, mild systemic hypothermia (MSH; rectal temperature 33 - 35 degrees C) was produced with a cooling blanket; and a control group was not exposed to hypothermia. Natural rewarming began after 3 days. Mean intracranial pressure 24, 48 or 72 h after injury was significantly lower in the SBC group than in the control group. Mean serum superoxide dismutase levels on Days 3 and 7 after injury in the SBC and MSH groups were significantly higher than in the control group. The percentage of patients with a good neurological outcome 2 years after injury was 72.7%, 57.1% and 34.8% in the SBC, MSH and control groups, respectively. Complications were managed without severe sequelae. Non-invasive SBC was safe and effective.

PMID 16604824  J Int Med Res. 2006 Jan-Feb;34(1):58-64. doi: 10.1177/1・・・
著者: Moulay Ahmed Bouderka, Bouchra Fakhir, Abderrahmane Bouaggad, Badreddine Hmamouchi, Driss Hamoudi, Abdeslam Harti
雑誌名: J Trauma. 2004 Aug;57(2):251-4.
Abstract/Text BACKGROUND: To see if early tracheostomy (fifth day) reduces duration of mechanical ventilation, ICU stay, incidence of pneumonia and mortality in comparison with prolonged intubation (PI) in patients with head injury.
METHODS: Patients were prospectively included in this study if they met the following criteria: isolated head injury, Glasgow coma scale (GCS) score < or =8 on first and fifth day, with cerebral contusion on CT scan. On the fifth day, randomization was done in two groups: early tracheostomy group (T group, n = 31) and prolonged endotracheal intubation group (I group, n = 31). We evaluated total time of mechanical ventilation, ICU stay, pneumonia incidence and mortality. Complications related to each technique were noted. Analysis of data were performed using Yates and Kruskall Walis tests. p < 0.05 was considered significant.
RESULTS: The two groups were comparable in term of age, sex, and Simplified Acute Physiologic Score (SAPS). The mean time of mechanical ventilatory support was shorter in T group (14.5 +/- 7.3) versus I group (17.5 +/- 10.6) (p = 0.02). After pneumonia was diagnosed, mechanical ventilatory time was 6 +/- 4.7 days for ET group versus 11.7 +/- 6.7 days for PEI group (p = 0.01). There was no difference in frequency of pneumonia or mortality between the two groups.
CONCLUSION: In severe head injury early tracheostomy decreases total days of mechanical ventilation or mechanical ventilation time after development of pneumonia.

PMID 15345969  J Trauma. 2004 Aug;57(2):251-4.
著者: H J Sugerman, L Wolfe, M D Pasquale, F B Rogers, K F O'Malley, M Knudson, L DiNardo, M Gordon, S Schaffer
雑誌名: J Trauma. 1997 Nov;43(5):741-7.
Abstract/Text OBJECTIVES: Determine the effect of early (days 3-5) or late (days 10-14) tracheostomy on intensive care unit length of stay (ICU LOS), frequency of pneumonia, and mortality, and evidence of short-term or long-term pharyngeal, laryngeal, or tracheal injury in head trauma, non-head trauma, and critically ill nontrauma patients.
STUDY DESIGN: Randomized, prospective.
SETTING: Five Level I trauma centers.
METHODS: Data were obtained prospectively and included Acute Physiology and Chronic Health Evaluation III score (AIII), Glasgow Coma Scale score, Emergency Room Trauma Score, Injury Severity Score, Acute Injury Score, type of endotracheal tube or tracheostomy, level of positive end-expiratory pressure, and peak inspiratory pressure. Patients were to undergo laryngoscopy for detection of injury according to the Lindholm criteria at the time of endotracheal tube or tracheostomy removal and be reevaluated at 3 to 5 months after discharge.
RESULTS: One hundred fifty-seven patients were entered, 127 to early randomization (3-5 days) and 28 to late randomization (10-14 days); however, only 112 patients with early and 14 with late randomization had completed data forms for the primary study goals. An additional 22 patients from the early entry groups were rerandomized late. Early randomization data: the AIII score was higher (p < 0.05) in the head trauma tracheostomy (65 +/- 4) than in the nontracheostomy group (51 +/- 4) and in the nontrauma tracheostomy (92 +/- 6) than in the nontracheostomy group (68 +/- 7), but was equivalent in the non-head trauma group. Glasgow Coma Scale score, Emergency Room Trauma Score, Injury Severity Score, Acute Injury Score, positive end-expiratory pressure, and peak inspiratory pressure were not significantly different in any of the groups. There were no significant differences in ICU LOS, frequency of pneumonia, or death in any of the groups after either early or late tracheostomy compared with continued endotracheal intubation. Only 83 patients underwent postextubation laryngoscopy. There were no significant differences between the groups; however, there were trends to more vocal cord ulceration and subglottic inflammation in the continued intubation group. No patient was seen in this study with late vocal cord or laryngeal stenosis; there were no tracheal-innominate artery fistulae. Seven of the patients with abnormal findings at extubation had normal 3- to 5-month postextubation laryngoscopy.
CONCLUSION: Physician bias limited patient entry into the study. Although there were higher AIII scores in the head trauma early tracheostomy patients, there were no differences in the primary end points of ICU LOS, pneumonia, or death in any of the groups studied. Long-term endoscopic follow-up was poor, but no known late tracheal stenosis was seen.

PMID 9390483  J Trauma. 1997 Nov;43(5):741-7.
著者: C Michael Dunham, Anthony F Cutrona, Brian S Gruber, Javier E Calderon, Kenneth J Ransom, Laurie L Flowers
雑誌名: Int J Burns Trauma. 2014;4(1):14-24. Epub 2014 Feb 22.
Abstract/Text OBJECTIVE: In the past, the authors performed a comprehensive literature review to identify all randomized controlled trials assessing the impact of early tracheostomy on severe brain injury outcomes. The search produced only two trials, one by Sugerman and another by Bouderka.
SUBJECTS AND METHODS: The current authors initiated an Institutional Review Board-approved severe brain injury randomized trial to evaluate the impact of early tracheostomy on ventilator-associated pneumonia rates, intensive care unit (ICU)/ventilator days, and hospital mortality. Current study results were compared with the other randomized trials and a meta-analysis was performed.
RESULTS: Early tracheostomy pneumonia rates were Sugerman-48.6%, Bouderka-58.1%, and current study-46.7%. No early tracheostomy pneumonia rates were Sugerman-53.1%, Bouderka-61.3%, and current study-44.4%. Pneumonia rate meta-analysis showed no difference for early tracheostomy and no early tracheostomy (OR 0.89; p = 0.71). Early tracheostomy ICU/ventilator days were Sugerman-16 ± 5.9, Bouderka-14.5 ± 7.3, and current study-14.1 ± 5.7. No early tracheostomy ICU/ventilator days were Sugerman-19 ± 11.3, Bouderka-17.5 ± 10.6, and current study-17 ± 5.4. ICU/ventilator day meta-analysis showed 2.9 fewer days with early tracheostomy (p = 0.02). Early tracheostomy mortality rates were Sugerman-14.3%, Bouderka-38.7%, and current study-0%. No early tracheostomy mortality rates were Sugerman-3.2%, Bouderka-22.6%, and current study-0%. Randomized trial mortality rate meta-analysis showed a higher rate for early tracheostomy (OR 2.68; p = 0.05). Because the randomized trials were small, a literature assessment was undertaken to find all retrospective studies describing the association of early tracheostomy on severe brain injury hospital mortality. The review produced five retrospective studies, with a total of 3,356 patients. Retrospective study mortality rate meta-analysis demonstrated a larger mortality for early tracheostomy (OR 1.97; p < 0.0001).
CONCLUSION: For severe brain injury, analyses indicate that ventilator-associated pneumonia rates are not decreased with early tracheostomy. Further, this study implies that mechanical ventilation is reduced with early tracheostomy. Both the randomized trial and retrospective meta-analysis indicate that risk for hospital death increases with early tracheostomy. Findings imply that early tracheostomy for severe brain injury is not a prudent routine policy.

PMID 24624310  Int J Burns Trauma. 2014;4(1):14-24. Epub 2014 Feb 22.
著者: Philippe Seguin, Michèle Tanguy, Bruno Laviolle, Olivier Tirel, Yannick Mallédant
雑誌名: Crit Care Med. 2006 May;34(5):1514-9. doi: 10.1097/01.CCM.0000214516.73076.82.
Abstract/Text OBJECTIVE: To evaluate the effect of a regular oropharyngeal application of povidone-iodine on the prevalence of ventilator-associated pneumonia in patients with severe head trauma.
DESIGN: Prospective randomized study.
SETTING: A surgical intensive care unit of a university hospital.
INTERVENTIONS: Patients with severe head trauma (Glasgow Coma Score of < or =8) expected to need ventilation for > or =2 days were prospectively randomized into three groups: those receiving nasopharynx and oropharynx rinsing with 20 mL of a 10% povidone-iodine aqueous solution, reconstituted in a 60-mL solution with sterile water (povidone-iodine group); those receiving nasopharynx and oropharynx rinsing with 60 mL of saline solution (saline group); or those undergoing a standard regimen without any instillation but with aspiration of oropharyngeal secretions (control group).
MEASUREMENTS AND MAIN RESULTS: The prevalence of ventilator-associated pneumonia was compared among the three groups. A total of 98 patients were analyzed (povidone-iodine group, n = 36; saline group, n = 31; and control group, n = 31). A total of 28 cases of ventilator-associated pneumonia were diagnosed. There was a significant decrease in the rate of ventilator-associated pneumonia in the povidone-iodine group when compared with the saline and control groups (3 of 36 patients [8%] vs. 12 of 31 patients [39%] and 13 of 31 patients [42%], respectively; p = .003 and .001, respectively). The length of stay and mortality in the surgical intensive care unit were not statistically different between the three groups.
CONCLUSIONS: The regular administration of povidone-iodine may be an effective strategy for decreasing the prevalence of ventilator-associated pneumonia in patients with severe head trauma.

PMID 16540962  Crit Care Med. 2006 May;34(5):1514-9. doi: 10.1097/01.C・・・
著者: Philippe Seguin, Bruno Laviolle, Claire Dahyot-Fizelier, Romain Dumont, Benoit Veber, Soizic Gergaud, Karim Asehnoune, Olivier Mimoz, Pierre-Yves Donnio, Eric Bellissant, Yannick Malledant, Study of Povidone Iodine to Reduce Pulmonary Infection in Head Trauma and Cerebral Hemorrhage Patients (SPIRIT) ICU Study Group, AtlanRéa Group
雑誌名: Crit Care Med. 2014 Jan;42(1):1-8. doi: 10.1097/CCM.0b013e3182a2770f.
Abstract/Text OBJECTIVE: To evaluate the efficacy and safety of oral care with povidone-iodine on the occurrence of ventilator-associated pneumonia in a high-risk population.
DESIGN: A multicenter, placebo-controlled, randomized, double-blind, two-parallel-group trial performed between May 2008 and May 2011.
SETTING: Six ICUs in France.
PATIENTS: One hundred seventy-nine severely brain-injured patients (Glasgow Coma Scale ≤ 8) or cerebral hemorrhage expected to be mechanically ventilated for more than 24 hours.
INTERVENTIONS: Participants were randomly assigned to receive oropharyngeal care with povidone-iodine (n = 91) or placebo (n = 88) six times daily until mechanical ventilation withdrawal.
MEASUREMENTS AND MAIN RESULTS: Primary endpoint was the rate of ventilator-associated pneumonia. Secondary endpoint included the rates of ventilator-associated tracheobronchitis and acute respiratory distress syndrome and patient's outcome. The number of patients evaluable for the primary endpoint (preplanned modified intention-to-treat population) was 150 (78 in the povidone-iodine group, 72 in the placebo group). Ventilator-associated pneumonia occurred in 24 patients (31%) in the povidone-iodine group and 20 (28%) in the placebo group (relative risk, 1.11 [95% CI, 0.67-1.82]; p = 0.69). There was no significant difference between the two groups for ventilator-associated tracheobronchitis: eight patients (10%) in the povidone-iodine group and five patients (7%) in the placebo group (relative risk, 1.48 [95% CI, 0.51-4.31]; p = 0.47). Acute respiratory distress syndrome occurred in five patients in the povidone-iodine group but not in the placebo group (p = 0.06). There was no difference between groups for ICU and hospital lengths of stay, as well as ICU and 90-day mortality.
CONCLUSIONS: There is no evidence to recommend oral care with povidone-iodine to prevent ventilator-associated pneumonia in high-risk patients. Furthermore, this strategy seems to increase the rate of acute respiratory distress syndrome.

PMID 24105456  Crit Care Med. 2014 Jan;42(1):1-8. doi: 10.1097/CCM.0b0・・・
著者: J M Sirvent, A Torres, M El-Ebiary, P Castro, J de Batlle, A Bonet
雑誌名: Am J Respir Crit Care Med. 1997 May;155(5):1729-34. doi: 10.1164/ajrccm.155.5.9154884.
Abstract/Text In comatose patients admitted to an ICU, particularly those with head injury, the incidence of early onset pneumonia is exceedingly high. We performed an open, prospective, randomized, and controlled clinical trial aiming at the reduction of the incidence of ventilator-associated pneumonia in head-injured patients and patients with stroke requiring mechanical ventilation. One hundred patients were included because of head injury or coma caused by medical stroke and with Glasgow coma scores < or = 12 and mechanical ventilation > 72 h. Patients eligible for the study (n = 50) received cefuroxime intravenously (two 1,500-mg doses 12 h apart after intubation) (the cefuroxime group) and 50 patients not receiving cefuroxime formed the control group. In the former group patients did not receive any other antibiotics before the end-point determination, whereas in the latter, 17 patients received prophylactic antibiotics as prescribed by the attending physician. The global incidence of microbiologically confirmed pneumonia was 37% (n = 37); 12 (24%) belonged to the cefuroxime group, and 25 (50%) belonged to the control group (p = 0.007). Early-onset pneumonia accounted for 70% of all the pneumonia episodes (n = 26), eight (67%) belonging to the cefuroxime group, and 18 (72%) belonging to the control group (p = 0.02). In the control group, four of 17 (23%) patients receiving prior antibiotics developed pneumonia, whereas 21 of 33 (64%) patients who did not receive antibiotics developed pneumonia (p = 0.016). The multivariate analysis revealed that the duration of mechanical ventilation (per each day) was an independent risk factor significantly associated to the development of pneumonia. Furthermore, the use of cefuroxime and/or prior antibiotics in the control group, before the pneumonia episode, had a protective effect against its development. No differences were found with regard to mortality and morbidity when comparing the study population with the control group. Nevertheless, when comparing patients with pneumonia (from both study and control groups) with those without it, there was a decrease in total hospital stay (35 +/- 13 versus 25 +/- 14 d, p = 0.048) and ICU stay (20 +/- 11 versus 11 +/- 7 d, p = 0.001). The study demonstrated that the administration of two single high doses 1,500 mg each of cefuroxime after the intubation of patients comatose because of head injury or medical stroke is an effective prophylactic strategy to decrease the incidence of ventilator-associated pneumonia.

PMID 9154884  Am J Respir Crit Care Med. 1997 May;155(5):1729-34. doi・・・
著者: Bernardo Ratilal, João Costa, Cristina Sampaio
雑誌名: J Neurosurg Pediatr. 2008 Jan;1(1):48-56. doi: 10.3171/PED-08/01/048.
Abstract/Text OBJECT: Systemic antibiotics and antibiotic-impregnated shunt (AIS) systems are often used to prevent shunt infection. The authors conducted a systematic review to evaluate its effectiveness of antibiotics in patients who underwent placement of intracranial ventricular shunts.
METHODS: The authors searched the Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE, LILACS, and the meeting proceedings from the American Association of Neurological Surgeons and from the European Association of Neurosurgical Societies until June 2005. Randomized and quasi-randomized trials comparing the use of prophylactic antibiotics (either systemic or AIS systems) in intracranial ventricular shunt procedures with placebo or no antibiotics were included in the review.
RESULTS: Seventeen trials involving 2134 patients were included. Results from the meta-analysis showed that the use of systemic antibiotic prophylaxis for internal shunts was associated with a decrease in shunt infection (odds ratio 0.51; 95% confidence interval 0.36-0.73). The authors found no significant differences between the subgroups evaluated in type of internal shunt (ventriculoperitoneal/ventriculoatrial), age, or duration of the administration of antibiotics.
CONCLUSIONS: The authors found a benefit of systemic prophylactic antibiotics in preventing shunt infection, regardless of the patient's age and the type of internal shunt used. The benefit of its use after the first 24 hours postoperatively remains uncertain. Future trials should be conducted to evaluate the effectiveness of different regimens of systemic antibiotics rather than placebo, namely single preoperative dose versus multiple doses. It should also be mandatory to evaluate the effectiveness of systemic prophylactic antibiotics for external ventricular drains. Evidence suggests that antibiotic-impregnated catheters reduce the incidence of shunt infection, although more well-designed clinical trials are needed.

PMID 18352803  J Neurosurg Pediatr. 2008 Jan;1(1):48-56. doi: 10.3171/・・・
著者: Xiang Wang, Yan Dong, Xiang-Qian Qi, Yi-Ming Li, Cheng-Guang Huang, Li-Jun Hou
雑誌名: Crit Care. 2013 Jul 25;17(4):234. doi: 10.1186/cc12608. Epub 2013 Jul 25.
Abstract/Text To assess the efficacy of antimicrobial-impregnated catheters in preventing catheter-related infections during external ventricular drainage (EVD), we performed a meta-analysis and systematic review. We systematically searched Medline, Embase, and the Cochrane Library. All randomized controlled trials (RCTs) and nonrandomized prospective studies (NPSs) related to antimicrobial-impregnated EVD catheters were included. The primary outcome was the rate of cerebrospinal fluid infection (CFI). The secondary outcomes included the rate of time-dependent CFI and catheter bacterial colonization. We further performed subgroup analysis, meta-regression analysis, and microbial spectrum analysis. Four RCTs and four NPSs were included. The overall rate of CFIs was 3.6% in the antimicrobial-impregnated catheter group and 13.7% in the standard catheter group. The pooled data demonstrated that antimicrobial-impregnated catheters were superior to standard catheters in lowering the rate of CFIs (odds ratio (OR) = 0.25, 95% confidence interval (CI) = 0.12 to 0.52, P <0.05). In survival analysis, the 20-day infection rate was significantly reduced with the use of antimicrobial-impregnated catheters (hazard ratio = 0.52, 95% CI = 0.29 to 0.95, P <0.05). Furthermore, a significantly decreased rate of catheter bacterial colonization was noticed for antimicrobial-impregnated catheters (OR = 0.37, 95% CI = 0.21 to 0.64, P <0.05). In subgroup analyses, although significant results remained for RCTs and NPSs, a subgroup difference was revealed (P <0.05). Compared with standard catheters, a significantly lower rate of CFIs was noticed for clindamycin/rifampin-impregnated catheters (OR = 0.27, 95% CI = 0.10 to 0.73, P <0.05) and for minocycline/rifampin-impregnated catheters (OR = 0.11, 95% CI = 0.06 to 0.21, P <0.05). However, no statistical significance was found when compared with silver-impregnated catheters (OR = 0.33, 95% CI = 0.07 to 1.69, P = 0.18). In microbial spectrum analysis, antimicrobial-impregnated catheters were shown to have a lower rate of Gram-positive bacterial infection, particularly the coagulase-negative Staphylococcus. In conclusion, the use of antimicrobial-impregnated EVD catheters could be beneficial for the prevention of CFI and catheter bacterial colonization. Although antibiotic-coated catheters seem to be effective, no sufficient evidence supports the efficacy of silver-impregnated catheters.

PMID 23890254  Crit Care. 2013 Jul 25;17(4):234. doi: 10.1186/cc12608.・・・
著者: K L Holloway, T Barnes, S Choi, R Bullock, L F Marshall, H M Eisenberg, J A Jane, J D Ward, H F Young, A Marmarou
雑誌名: J Neurosurg. 1996 Sep;85(3):419-24. doi: 10.3171/jns.1996.85.3.0419.
Abstract/Text The investigators undertook a retrospective analysis of ventriculostomy infections to evaluate their relationship to monitoring duration and prophylactic catheter exchange. In 1984, the results of an epidemiological study of ventriculostomy-related infection were published. One of the conclusions of the paper was that the incidence of ventriculostomy-related infections rose after 5 days of monitoring. This led to the recommendation that catheters be prophylactically changed at 5-day intervals if prolonged monitoring was required. A recent randomized prospective study on central venous catheters showed no reduction in infection with prophylactic catheter exchanges. This has led the authors to reexamine their experience with ventriculostomy infections. Data on 584 severely head injured patients with ventriculostomies were prospectively collected in two data banks, The Traumatic Coma Data Bank and The Medical College of Virginia Neurocore Data Bank. These data were retrospectively analyzed for factors associated with ventriculostomy related infections. It was found that there is a relationship of ventriculitis to monitoring duration but it is not simple or linear. There is a rising risk of infection over the first 10 days, but infection then becomes very unlikely despite a population that continues to be at risk. Patients in whom catheters were replaced prior to 5 days did not have a lower infection rate than those whose catheters were exchanged at more than 5-day intervals. Based on these data, it is recommended that ventriculostomy catheters for intracranial pressure monitoring be removed as quickly as possible, and in circumstances in which prolonged monitoring is required, there appears to be no benefit from catheter exchange.

PMID 8751626  J Neurosurg. 1996 Sep;85(3):419-24. doi: 10.3171/jns.19・・・
著者: Alan P Lozier, Robert R Sciacca, Mario F Romagnoli, E Sander Connolly
雑誌名: Neurosurgery. 2002 Jul;51(1):170-81; discussion 181-2.
Abstract/Text OBJECTIVE: To provide a critical evaluation of the published literature describing risk factors for ventriculostomy-related infections (VRIs) and the efficacy of prophylactic catheter exchange.
METHODS: A MEDLINE literature search was performed, and data were extracted from studies published from 1941 through 2001.
RESULTS: Published criteria for diagnosing VRIs are highly variable. Intraventricular hemorrhage, subarachnoid hemorrhage, cranial fracture with cerebrospinal fluid leak, craniotomy, systemic infections, and catheter irrigation all predispose patients to the development of VRIs. Extended duration of catheterization is correlated with an increasing risk of cerebrospinal fluid infections during the first 10 days of catheterization. Prophylactic catheter exchange does not modify the risk of developing later VRIs in retrospective studies.
CONCLUSION: Categorizing suspected cerebrospinal fluid infections as contaminants, colonization, suspected or confirmed VRIs, or ventriculitis more accurately describes the patient's clinical condition and may indicate different management strategies. A prospective, randomized clinical trial is required to further evaluate the efficacy of prophylactic catheter exchange in limiting the incidence of VRIs during prolonged catheterization. Although prophylactic catheter exchange remains a practice option, the available data suggest that this procedure is not currently justified.

PMID 12182415  Neurosurgery. 2002 Jul;51(1):170-81; discussion 181-2.
著者: A H Hsieh, M J Bishop, P S Kubilis, D W Newell, D J Pierson
雑誌名: Am Rev Respir Dis. 1992 Aug;146(2):290-4. doi: 10.1164/ajrccm/146.2.290.
Abstract/Text Pneumonia is common among patients with artificial airways in place. Most prior studies of such pneumonia involve a heterogeneous group of patients, usually with major medical or surgical illnesses. We studied the incidence of pneumonia in a group of patients with isolated closed head injury (CHI) in an effort to determine the pattern of the problem in the absence of other injuries and to determine whether the pattern of development of pneumonia in these patients was comparable to that in more heterogeneous groups of mechanically ventilated patients. We studied 109 initially comatose patients with isolated CHI who were ventilated 24 h or more. The mean age was 30.3 +/- 20.2 yr, 72% were male, and the admission Glasgow coma score was 4.9T +/- 1.4. Overall, 45 patients (41%) developed pneumonia, with the majority (29/45) occurring during the first 3 days of hospitalization. No patient developed pneumonia after the first week despite the fact that many were still ventilated, others remained intubated, and yet others were extubated but comatose. Patients who developed pneumonia experienced a longer ICU stay (10.5 +/- 5.4 days versus 7.2 +/- 4.3 days, p = 0.001) and hospital stay (34.8 +/- 27.6 versus 22.5 +/- 20.2 days, p = 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID 1489114  Am Rev Respir Dis. 1992 Aug;146(2):290-4. doi: 10.1164/・・・
著者: Mitchell J Daley, Sadia Ali, Carlos V R Brown
雑誌名: Am Surg. 2015 Feb;81(2):207-11.
Abstract/Text The objective of this study is to compare rates of venous thromboembolism (VTE) in patients who receive enoxaparin prophylaxis compared with no enoxaparin prophylaxis after craniotomy for traumatic brain injury (TBI). This retrospective cohort evaluated all trauma patients admitted to a Level I trauma center from January 2006 to December 2011 who received craniotomy after acute TBI. Patients were excluded if developed VTE before administration of enoxaparin or they died within the first 72 hours of hospital admission. A total of 271 patients were included (enoxaparin prophylaxis, n = 45; no enoxaparin prophylaxis, n = 225). The median time until enoxaparin initiation was 11 ± 1 days. There was no significant difference in the proportion of patients who developed a VTE when using enoxaparin prophylaxis compared with no enoxaparin prophylaxis (2 vs 4%; P = 0.65). Rates of deep vein thrombosis (2 vs 3%; P = 0.87) and pulmonary embolism (0 vs 1%; P = 0.99) were similar between treatment groups, respectively. Late enoxaparin prophylaxis did not demonstrate a protective effect for VTE. Given the overall low event rate, the administration of pharmacologic prophylaxis against VTE late in the treatment course may not be routinely warranted after craniotomy for acute TBI. Further investigation with early administration of enoxaparin is needed.

PMID 25642886  Am Surg. 2015 Feb;81(2):207-11.
著者: Michael E Kwiatt, Mitul S Patel, Steven E Ross, Mary T Lachant, Heather G MacNew, M Gage Ochsner, Scott H Norwood, LaDonna Speier, Rosemary Kozar, Jonathan A Gerber, Susan Rowell, Sheetal Krishnakumar, David H Livingston, George Manis, James M Haan
雑誌名: J Trauma Acute Care Surg. 2012 Sep;73(3):625-8. doi: 10.1097/TA.0b013e318265cab9.
Abstract/Text BACKGROUND: Venous thromboembolism (VTE) is a significant risk in trauma patients. Although low-molecular weight heparin (LMWH) is effective in VTE prophylaxis, its use for patients with traumatic intracranial hemorrhage remains controversial. The purpose of this study was to evaluate the safety of LMWH for VTE prophylaxis in blunt intracranial injury.
METHODS: We conducted a retrospective multicenter study of LMWH chemoprophylaxis on patients with intracranial hemorrhage caused by blunt trauma. Patients with brain Abbreviated Injury Scale score of 3 or higher, age 18 years or older, and at least one repeated head computed tomographic scan were included. Patients with previous VTE; on preinjury anticoagulation; hospitalized for less than 48 hours; on heparin for VTE prophylaxis; or required emergent thoracic, abdominal, or vascular surgery at admission were excluded. Patients were divided into two groups: those who received LMWH and those who did not. The primary outcome was progression of intracranial hemorrhage on repeated head computed tomographic scan.
RESULTS: The study included 1,215 patients, of which 220 patients (18.1%) received LMWH and 995 (81.9%) did not. Hemorrhage progression occurred in 239 of 995 control subjects and 93 of 220 LMWH patients (24% vs. 42%, p < 0.001). Hemorrhage progression occurred in 32 patients after initiating LMWH (14.5%). Nine of these patients (4.1%) required neurosurgical intervention for hemorrhage progression.
CONCLUSION: Patients receiving LMWH were at higher risk for hemorrhage progression. We were unable to demonstrate safety of LMWH for VTE prophylaxis in patients with brain injury. The risk of using LMWH may exceed its benefit.
LEVEL OF EVIDENCE: Therapeutic study, level IV.

Copyright © 2012 by Lippincott Williams & Wilkins.
PMID 22929493  J Trauma Acute Care Surg. 2012 Sep;73(3):625-8. doi: 10・・・
著者: Shahin Mohseni, Peep Talving, Lydia Lam, Linda S Chan, Crystal Ives, Demetrios Demetriades
雑誌名: J Emerg Trauma Shock. 2012 Jan;5(1):11-5. doi: 10.4103/0974-2700.93102.
Abstract/Text OBJECTIVE: The purpose of this study was to investigate the effect of prophylactic anticoagulation on the incidence of venous thromboembolic events (VTE) in patients suffering from isolated severe traumatic brain injury (TBI).
MATERIALS AND METHODS: Retrospective matched case-control study in adult patients sustaining isolated severe TBI (head AIS ≥3, with extracranial AIS ≤2) receiving VTE prophylaxis while in the surgical intensive care unit from 1/2007 through 12/2009. Patients subjected to VTE prophylaxis were matched 1:1 by age, gender, glasgow coma scale (GCS) score at admission, presence of hypotension on admission, injury severity score, and head abbreviated injury scale (AIS) score, with patients who did not receive chemical VTE prophylaxis. The primary outcome measure was VTE. Secondary outcomes were SICU and hospital length of stay (HLOS), adverse effects of anticoagulation, and mortality.
RESULTS: After propensity matching, 37 matched pairs were analysed. Cases and controls had similar demographics, injury characteristics, rate of craniotomies/craniectomies, SICU LOS, and HLOS. The median time of commencement of VTE prophylaxis was 10 days. The incidence of VTE was increased 3.5-fold in the controls compared to the cases (95% CI 1.0-12.1, P=0.002). The mortality was higher in patients who did not receive anticoagulation (19% vs. 5%, P=0.001). No adverse outcomes were detected in the anticoagulated patients.
CONCLUSION: Prophylactic anticoagulation decreases the overall risk for clinically significant VTE in patients with severe isolated TBI. Prospective validation of the timing and safety of chemical VTE prophylaxis in these instances is warranted.

PMID 22416148  J Emerg Trauma Shock. 2012 Jan;5(1):11-5. doi: 10.4103/・・・
著者: Travis Scudday, Karen Brasel, Travis Webb, Panna Codner, Lewis Somberg, John Weigelt, David Herrmann, William Peppard
雑誌名: J Am Coll Surg. 2011 Jul;213(1):148-53; discussion 153-4. doi: 10.1016/j.jamcollsurg.2011.02.027. Epub 2011 Apr 3.
Abstract/Text BACKGROUND: Patients with traumatic brain injury (TBI) are at high risk for venous thromboembolism (VTE), but physicians are cautious with chemical prophylaxis in these patients because of concern about exacerbating intracranial hemorrhage. We hypothesized that early use of chemical thromboprophylaxis would reduce VTE incidence without increasing intracranial hemorrhage.
STUDY DESIGN: Records of all patients admitted with a TBI to a Level I trauma center from 2006 to 2008 were reviewed. TBI was defined as intracranial hemorrhage, hematoma, contusion, or diffuse axonal injury with a head Abbreviated Injury Scale score >2. Patients were excluded if they were discharged or died within 72 hours of admission. Chemical prophylaxis was defined as subcutaneous or intravenous unfractionated heparin or low molecular weight heparin before any VTE diagnosis. Progression of TBI was defined by worsening CT findings. VTE was defined as deep venous thrombosis or pulmonary embolus confirmed by radiology reports. Primary outcomes were progression of hemorrhage and VTE events.
RESULTS: Eight hundred and twelve of the 1,258 patients admitted to the trauma center with a TBI met study criteria. Chemical thromboprophylaxis was given to 49.5% (n = 402). Mean head Abbreviated Injury Scale score was 3.4 in both groups. One hundred and sixty-nine patients started prophylaxis within 48 hours and 242 patients began within 72 hours. Patients receiving chemical prophylaxis had a lower incidence of VTE (1% versus 3%; p = 0.019). Although not statistically significant, they also had a lower rate of injury progression, 3% versus 6% (p = 0.055).
CONCLUSIONS: Use of chemical thromboprophylaxis in TBI patients with a stable or improved head CT after 24 hours substantially reduces the incidence of VTE and does not increase the risk of progression of intracranial hemorrhage.

Copyright © 2011 American College of Surgeons. Published by Elsevier Inc. All rights reserved.
PMID 21459632  J Am Coll Surg. 2011 Jul;213(1):148-53; discussion 153-・・・
著者: Ali Farooqui, Bradley Hiser, Stephen L Barnes, N Scott Litofsky
雑誌名: J Neurosurg. 2013 Dec;119(6):1576-82. doi: 10.3171/2013.8.JNS13424. Epub 2013 Sep 20.
Abstract/Text OBJECT: Patients with traumatic brain injury (TBI) are at risk for development of thromboembolic disease. The use of chemoprophylaxis in this patient group has not fully been characterized. The authors hypothesize that early chemoprophylaxis in patients with TBI is safe and efficacious.
METHODS: In May 2009, a protocol was instituted for patients with TBI where chemoprophylaxis for thromboembolic disease (either 30 mg of Lovenox twice daily or 5000 U of heparin 3 times a day) was initiated 24 hours after an intracranial hemorrhage (ICH) was demonstrated as stable on head CT image. Two cohorts were evaluated: Cohort A included patients from May 2008 through April 2009 who had no routine administration of chemoprophylaxis, and Cohort B included patients from May 2009 through May 2010 after the protocol was instituted. The groups were compared, with the major outcomes being deep venous thrombosis (DVT), pulmonary embolism, and increase in size of ICH.
RESULTS: Of the 312 patients with TBI who were seen during the study course, 236 patients met criteria for inclusion in the study: 107 patients in Cohort A and 129 patients in Cohort B. The DVT rate was 6 occurrences (5.61%) in Cohort A and 0 occurrences (0%) in Cohort B, which was a statistically significant difference (p = 0.0080). Pulmonary embolism was found in 4 patients (3.74%) in Cohort A and 1 patient (0.78%) in Cohort B, a difference that did not reach statistical significance (p = 0.18). Three instances (2.8%) in Cohort A and 1 instance (0.7%) in Cohort B of increased ICH occurred after starting anticoagulation for chemoprophylaxis; this was not statistically different (p = 0.33).
CONCLUSIONS: Use of chemoprophylaxis in TBI 24 hours after stable head CT is safe and decreases the rate of DVT formation.

PMID 24053504  J Neurosurg. 2013 Dec;119(6):1576-82. doi: 10.3171/2013・・・
著者: Christopher M Nickele, Timothy K Kamps, Joshua E Medow
雑誌名: Neurocrit Care. 2013 Apr;18(2):184-92. doi: 10.1007/s12028-012-9786-x.
Abstract/Text BACKGROUND: Venous thromboembolism (VTE) is a complication that affects approximately 30 % of moderate and severe traumatic brain injury (TBI) patients when pharmacologic prophylaxis is not used. Following TBI, specifically in the case of contusions, the safety and efficacy of pharmacologic thromboembolism prophylaxis (PTP) has been studied only in small sample sizes. In this study, we attempt to assess the safety and efficacy of a PTP protocol for TBI patients, as a quality improvement (QI) initiative, in the neuroscience intensive care unit (NSICU).
METHODS: Between January 1st and December 31st, 2009, consecutive patients discharged from the University of Wisconsin NSICU after >a 48 h minimum stay were evaluated as part of a QI project. A protocol for the initiation of PTP was designed and implemented for NSICU patients. The protocol did not vary based on type of intracranial injury. The rate of VTE was reported as was heparin-induced thrombocytopenia and PTP-related expansion of intracranial hemorrhage (IH) requiring reoperation. The number of patients receiving PTP and the timing of therapy were tracked. Patients were excluded for persistent coagulopathy, other organ system bleeding (such as the gastrointestinal tract), or pregnancy. Faculty could opt out of the protocol without reason. Using the same criteria, patients discharged during the preceding 6 months, from July 1st to December 31st, 2008, were evaluated as controls as the PTP protocol was not in effect during this time.
RESULTS: During the control period, there were 48 head trauma admissions who met the inclusion criteria. In 22 patients (45.8 %), PTP was initiated at an average of 4.9 ± 5.4 days after admission. During the protocol period, there were 87 head trauma admissions taken from 1,143 total NSICU stays who met criteria. In 63 patients (72.4 %), the care team in the NSICU successfully initiated PTP, at an average of 3.4 ± 2.8 days after admission. All 87 trauma patients were analyzed, and the rate of clinically significant deep venous thrombosis (DVT) was 6.9 % (6 of 87). Three protocol patients (3.45 %) went to the operating room for surgery after the initiation of PTP; none of these patients had a measurable change in hemorrhage size on head CT. The change in percentage of patients receiving PTP was significantly increased by the protocol (p < 0.0001); while the average days to first PTP dose trended down with institution of the protocol, this change was not statistically significant.
CONCLUSION: A PTP protocol in the NSICU is useful in controlling the number of complications from DVT and pulmonary embolism while avoiding additional IH. This protocol, based on a published body of literature, allowed for VTE rates similar to published rates, while having no PTP-related hemorrhage expansion. The protocol significantly changed physician behavior, increasing the percentage of patients receiving PTP during their hospitalization; whether long-term patient outcomes are affected is a potential goal for future study.

PMID 23099845  Neurocrit Care. 2013 Apr;18(2):184-92. doi: 10.1007/s12・・・
著者: Robert B Page, Mary Ann Spott, Satish Krishnamurthy, Christopher Taleghani, Vernon M Chinchilli
雑誌名: Neurosurgery. 2004 Jan;54(1):143-8; discussion 148-9.
Abstract/Text OBJECTIVE: We retrospectively examined the database of the Pennsylvania Trauma Systems Foundation to determine the risk of pulmonary embolism in adult patients sustaining isolated head trauma or multiple injuries, including head trauma, to answer two questions: What is the incidence of symptomatic pulmonary embolism during hospitalization in a trauma center in patients who have sustained a head injury? Are patients with head injuries more at risk for pulmonary embolism than trauma patients without head injuries?
METHODS: We determined the total number of adult submissions per year to the Pennsylvania Trauma Outcomes Study from 1992 to 1996. Age, sex, Glasgow Coma Scale score, Abbreviated Injury Score for head injury, Injury Severity Score, intensive care unit days, hospital days, and the presence or absence of head injury, spinal injury, pelvic fractures, and/or femur fractures were recorded. Statistical techniques to evaluate their correlation with the incidence of pulmonary embolism included chi(2) testing, linear regression analysis, Kendall analysis, and logistic regression analysis.
RESULTS: The average incidence of symptomatic pulmonary embolism in head-injured patients occurring during their acute hospital stay was 0.38%. This rate was not significantly greater than the 0.27% incidence of pulmonary embolism in patients without head injury. Factors that significantly increased this incidence were age greater than 45 years, Injury Severity Score greater than 15, male sex, and the presence of pelvic or femur fractures or of spinal cord injury.
CONCLUSION: We found no evidence that head injury is a significant independent risk factor for development of symptomatic pulmonary embolism during the acute hospitalization of the trauma patient.

PMID 14683551  Neurosurgery. 2004 Jan;54(1):143-8; discussion 148-9.
著者: Scott H Norwood, Clyde E McAuley, John D Berne, Van L Vallina, D Brent Kerns, Thomas W Grahm, Kevin Short, Jerry W McLarty
雑誌名: Arch Surg. 2002 Jun;137(6):696-701; discussion 701-2.
Abstract/Text BACKGROUND: Patients with traumatic intracranial hemorrhagic injuries (IHIs) are at high risk for venous thromboembolism (VTE). The safety of early anticoagulation for IHI has not been established.
HYPOTHESIS: Enoxaparin can be safely administered to most patients with IHI for VTE prophylaxis.
SETTING: Level I trauma center.
DESIGN: Prospective, single-cohort, observational study.
PATIENTS AND METHODS: One hundred fifty (85%) of 177 patients with blunt IHI received enoxaparin beginning approximately 24 hours after hospital admission until discharge. Brain computed tomographic (CT) scans were performed at admission, 24 hours after admission, and at variable intervals thereafter based on clinical course. Patients were excluded for coagulopathy, heparin allergy, expected brain death or discharge within 48 hours, and age younger than 14 years. Complications of enoxaparin prophylaxis were defined as Marshall CT grade progression of IHI, expansion of an existing IHI, or development of a new hemorrhagic lesion on follow-up CT after beginning enoxaparin use.
RESULTS: Thirty-four patients (23%) had CT progression of IHI. Twenty-eight CT scans (19%) worsened before enoxaparin therapy and 6 (4%) worsened after beginning enoxaparin use. No differences between operative patient (2/24, 8%) and nonoperative patient (4/126, 3%) complications were identified (P =.23). Study group mortality was 7% (10/150). All 6 patients who developed progression of IHI after initiation of enoxaparin therapy survived hospitalization. A deep vein thrombosis was identified in 2 (2%) of 106 patients.
CONCLUSION: Enoxaparin can be safely used for VTE prophylaxis in trauma patients with IHI when started 24 hours after hospital admission or after craniotomy.

PMID 12049541  Arch Surg. 2002 Jun;137(6):696-701; discussion 701-2.
著者: Aziz S Alali, Robert A Fowler, Todd G Mainprize, Damon C Scales, Alexander Kiss, Charles de Mestral, Joel G Ray, Avery B Nathens
雑誌名: J Neurotrauma. 2013 Oct 15;30(20):1737-46. doi: 10.1089/neu.2012.2802. Epub 2013 Jul 11.
Abstract/Text Although existing guidelines support the utilization of intracranial pressure (ICP) monitoring in patients with traumatic brain injury (TBI), the evidence suggesting benefit is limited. To evaluate the impact on outcome, we determined the relationship between ICP monitoring and mortality in centers participating in the American College of Surgeons Trauma Quality Improvement Program (TQIP). Data on 10,628 adults with severe TBI were derived from 155 TQIP centers over 2009-2011. Random-intercept multilevel modeling was used to evaluate the association between ICP monitoring and mortality after adjusting for important confounders. We evaluated this relationship at the patient level and at the institutional level. Overall mortality (n=3769) was 35%. Only 1874 (17.6%) patients underwent ICP monitoring, with a mortality of 32%. The adjusted odds ratio (OR) for mortality was 0.44 [95% confidence interval (CI), 0.31-0.63], when comparing patients with ICP monitoring to those without. It is plausible that patients receiving ICP monitoring were selected because of an anticipated favorable outcome. To overcome this limitation, we stratified hospitals into quartiles based on ICP monitoring utilization. Hospitals with higher rates of ICP monitoring use were associated with lower mortality: The adjusted OR of death was 0.52 (95% CI, 0.35-0.78) in the quartile of hospitals with highest use, compared to the lowest. ICP monitoring utilization rates explained only 9.9% of variation in mortality across centers. Results were comparable irrespective of the method of case-mix adjustment. In this observational study, ICP monitoring utilization was associated with lower mortality. However, variability in ICP monitoring rates contributed only modestly to variability in institutional mortality rates. Identifying other institutional practices that impact on mortality is an important area for future research.

PMID 23731257  J Neurotrauma. 2013 Oct 15;30(20):1737-46. doi: 10.1089・・・
著者: Randall M Chesnut, Nancy Temkin, Nancy Carney, Sureyya Dikmen, Carlos Rondina, Walter Videtta, Gustavo Petroni, Silvia Lujan, Jim Pridgeon, Jason Barber, Joan Machamer, Kelley Chaddock, Juanita M Celix, Marianna Cherner, Terence Hendrix, Global Neurotrauma Research Group
雑誌名: N Engl J Med. 2012 Dec 27;367(26):2471-81. doi: 10.1056/NEJMoa1207363. Epub 2012 Dec 12.
Abstract/Text BACKGROUND: Intracranial-pressure monitoring is considered the standard of care for severe traumatic brain injury and is used frequently, but the efficacy of treatment based on monitoring in improving the outcome has not been rigorously assessed.
METHODS: We conducted a multicenter, controlled trial in which 324 patients 13 years of age or older who had severe traumatic brain injury and were being treated in intensive care units (ICUs) in Bolivia or Ecuador were randomly assigned to one of two specific protocols: guidelines-based management in which a protocol for monitoring intraparenchymal intracranial pressure was used (pressure-monitoring group) or a protocol in which treatment was based on imaging and clinical examination (imaging-clinical examination group). The primary outcome was a composite of survival time, impaired consciousness, and functional status at 3 months and 6 months and neuropsychological status at 6 months; neuropsychological status was assessed by an examiner who was unaware of protocol assignment. This composite measure was based on performance across 21 measures of functional and cognitive status and calculated as a percentile (with 0 indicating the worst performance, and 100 the best performance).
RESULTS: There was no significant between-group difference in the primary outcome, a composite measure based on percentile performance across 21 measures of functional and cognitive status (score, 56 in the pressure-monitoring group vs. 53 in the imaging-clinical examination group; P=0.49). Six-month mortality was 39% in the pressure-monitoring group and 41% in the imaging-clinical examination group (P=0.60). The median length of stay in the ICU was similar in the two groups (12 days in the pressure-monitoring group and 9 days in the imaging-clinical examination group; P=0.25), although the number of days of brain-specific treatments (e.g., administration of hyperosmolar fluids and the use of hyperventilation) in the ICU was higher in the imaging-clinical examination group than in the pressure-monitoring group (4.8 vs. 3.4, P=0.002). The distribution of serious adverse events was similar in the two groups.
CONCLUSIONS: For patients with severe traumatic brain injury, care focused on maintaining monitored intracranial pressure at 20 mm Hg or less was not shown to be superior to care based on imaging and clinical examination. (Funded by the National Institutes of Health and others; ClinicalTrials.gov number, NCT01068522.).

PMID 23234472  N Engl J Med. 2012 Dec 27;367(26):2471-81. doi: 10.1056・・・
著者: Arash Farahvar, Linda M Gerber, Ya-Lin Chiu, Nancy Carney, Roger Härtl, Jamshid Ghajar
雑誌名: J Neurosurg. 2012 Oct;117(4):729-34. doi: 10.3171/2012.7.JNS111816. Epub 2012 Aug 17.
Abstract/Text OBJECT: Evidence-based guidelines recommend intracranial pressure (ICP) monitoring for patients with severe traumatic brain injury (TBI), but there is limited evidence that monitoring and treating intracranial hypertension reduces mortality. This study uses a large, prospectively collected database to examine the effect on 2-week mortality of ICP reduction therapies administered to patients with severe TBI treated either with or without an ICP monitor.
METHODS: From a population of 2134 patients with severe TBI (Glasgow Coma Scale [GCS] Score <9), 1446 patients were treated with ICP-lowering therapies. Of those, 1202 had an ICP monitor inserted and 244 were treated without monitoring. Patients were admitted to one of 20 Level I and two Level II trauma centers, part of a New York State quality improvement program administered by the Brain Trauma Foundation between 2000 and 2009. This database also contains information on known independent early prognostic indicators of mortality, including age, admission GCS score, pupillary status, CT scanning findings, and hypotension.
RESULTS: Age, initial GCS score, hypotension, and CT scan findings were associated with 2-week mortality. In addition, patients of all ages treated with an ICP monitor in place had lower mortality at 2 weeks (p = 0.02) than those treated without an ICP monitor, after adjusting for parameters that independently affect mortality.
CONCLUSIONS: In patients with severe TBI treated for intracranial hypertension, the use of an ICP monitor is associated with significantly lower mortality when compared with patients treated without an ICP monitor. Based on these findings, the authors conclude that ICP-directed therapy in patients with severe TBI should be guided by ICP monitoring.

PMID 22900846  J Neurosurg. 2012 Oct;117(4):729-34. doi: 10.3171/2012.・・・
著者: Peep Talving, Efstathios Karamanos, Pedro G Teixeira, Dimitra Skiada, Lydia Lam, Howard Belzberg, Kenji Inaba, Demetrios Demetriades
雑誌名: J Neurosurg. 2013 Nov;119(5):1248-54. doi: 10.3171/2013.7.JNS122255. Epub 2013 Aug 23.
Abstract/Text OBJECT: The Brain Trauma Foundation (BTF) has established guidelines for intracranial pressure (ICP) monitoring in severe traumatic brain injury (TBI). This study assessed compliance with these guidelines and the effect on outcomes.
METHODS: This is a prospective, observational study including patients with severe blunt TBI (Glasgow Coma Scale score ≤ 8, head Abbreviated Injury Scale score ≥ 3) between January 2010 and December 2011. Demographics, clinical characteristics, laboratory profile, head CT scans, injury severity indices, and interventions were collected. The study population was stratified into 2 study groups: ICP monitoring and no ICP monitoring. Primary outcomes included compliance with BTF guidelines, overall in-hospital mortality, and mortality due to brain herniation. Secondary outcomes were ICU and hospital lengths of stay. Multiple regression analyses were deployed to determine the effect of ICP monitoring on outcomes.
RESULTS: A total of 216 patients met the BTF guideline criteria for ICP monitoring. Compliance with BTF guidelines was 46.8% (101 patients). Patients with subarachnoid hemorrhage and those who underwent craniectomy/craniotomy were significantly more likely to undergo ICP monitoring. Hypotension, coagulopathy, and increasing age were negatively associated with the placement of ICP monitoring devices. The overall in-hospital mortality was significantly higher in patients who did not undergo ICP monitoring (53.9% vs 32.7%, adjusted p = 0.019). Similarly, mortality due to brain herniation was significantly higher for the group not undergoing ICP monitoring (21.7% vs 12.9%, adjusted p = 0.046). The ICU and hospital lengths of stay were significantly longer in patients subjected to ICP monitoring.
CONCLUSIONS: Compliance with BTF ICP monitoring guidelines in our study sample was 46.8%. Patients managed according to the BTF ICP guidelines experienced significantly improved survival.

PMID 23971954  J Neurosurg. 2013 Nov;119(5):1248-54. doi: 10.3171/2013・・・
著者: Linda M Gerber, Ya-Lin Chiu, Nancy Carney, Roger Härtl, Jamshid Ghajar
雑誌名: J Neurosurg. 2013 Dec;119(6):1583-90. doi: 10.3171/2013.8.JNS13276. Epub 2013 Oct 8.
Abstract/Text OBJECT: In spite of evidence that use of the Brain Trauma Foundation Guidelines for the Management of Severe Traumatic Brain Injury (Guidelines) would dramatically reduce morbidity and mortality, adherence to these Guidelines remains variable across trauma centers. The authors analyzed 2-week mortality due to severe traumatic brain injury (TBI) from 2001 through 2009 in New York State and examined the trends in adherence to the Guidelines.
METHODS: The authors calculated trends in adherence to the Guidelines and age-adjusted 2-week mortality rates between January 1, 2001, and December 31, 2009. Univariate and multivariate logistic regression analyses were performed to evaluate the effect of time period on case-fatality. Intracranial pressure (ICP) monitor insertion was modeled in a 2-level hierarchical model using generalized linear mixed effects to allow for clustering by different centers.
RESULTS: From 2001 to 2009, the case-fatality rate decreased from 22% to 13% (p < 0.0001), a change that remained significant after adjusting for factors that independently predict mortality (adjusted OR 0.52, 95% CI 0.39-0.70; p < 0.0001). Guidelines adherence increased, with the percentage of patients with ICP monitoring increasing from 56% to 75% (p < 0.0001). Adherence to cerebral perfusion pressure treatment thresholds increased from 15% to 48% (p < 0.0001). The proportion of patients having an ICP elevation greater than 25 mm Hg dropped from 42% to 29% (p = 0.0001).
CONCLUSIONS: There was a significant reduction in TBI mortality between 2001 and 2009 in New York State. Increase in Guidelines adherence occurred at the same time as the pronounced decrease in 2-week mortality and decreased rate of intracranial hypertension, suggesting a causal relationship between Guidelines adherence and improved outcomes. Our findings warrant future investigation to identify methods for increasing and sustaining adherence to evidence-based Guidelines recommendations.

PMID 24098983  J Neurosurg. 2013 Dec;119(6):1583-90. doi: 10.3171/2013・・・
著者: Sheng-Jean Huang, Wei-Chen Hong, Yin-Yi Han, Yuan-Sen Chen, Chung-Shi Wen, Yi-Shin Tsai, Yong-Kwang Tu
雑誌名: J Clin Neurosci. 2006 Oct;13(8):818-22. doi: 10.1016/j.jocn.2005.11.034. Epub 2006 Sep 5.
Abstract/Text In the past 5 years, cerebral perfusion pressure (CPP) management has become the standard in the treatment of severe head injuries. Guidelines published in 2000 suggest that CPP should be at least 70 mmHg; however, there is still debate about the optimal CPP. The purpose of the present study was to evaluate the effectiveness of these three widely used therapies: (i) intracranial pressure (ICP) targeted; (ii) CPP-targeted with CPP >70 mmHg; and (iii) modified CPP-targeted (mCPP) therapy with CPP >60 mmHg. The clinical procedures, complications and outcomes of patients in the different groups were compared. Data, including patient age, sex, initial Glasgow Coma Scale, ICP, CPP, fluid status, amount of mannitol and vasopressor used, daily fluid intake and output, complications and clinical results, were collected from 213 patients with severe head injuries over a 12-year period. Patients were categorized into three groups (ICP, CPP, mCPP) according to the treatment protocol used. Retrospective data collection was performed by chart review. The mortality rate was 28.6%, 14.3% and 13.5% in the ICP, CPP, and mCPP groups, respectively. Highest intake/output ratio, amount of vasopressor used and pulmonary complications were seen in the CPP patients. The mCPP patients showed the best clinical outcome and lowest complication rate. Although CPP-targeted therapy is the most recommended therapeutic protocol, our data show that patients treated with modified CPP-target therapy with CPP >60 mmHg have better clinical outcomes and fewer complications.

PMID 16908157  J Clin Neurosci. 2006 Oct;13(8):818-22. doi: 10.1016/j.・・・
著者: Ross P Martini, Steven Deem, N David Yanez, Randall M Chesnut, Noel S Weiss, Stephen Daniel, Michael Souter, Miriam M Treggiari
雑誌名: J Neurosurg. 2009 Oct;111(4):644-9. doi: 10.3171/2009.2.JNS08998.
Abstract/Text OBJECT: The authors sought to describe changes in clinical management associated with brain tissue oxygen (PbO(2)) monitoring and how these changes affected outcomes and resource utilization.
METHODS: The cohort study comprised 629 patients admitted to a Level I trauma center with a diagnosis of severe traumatic brain injury over a period of 3 years. Hospital mortality rate, neurological outcome, and resource utilization of 123 patients who underwent both PbO(2) and intracranial pressure (ICP) monitoring were compared with the same measures in 506 patients who underwent ICP monitoring only. The main outcomes were hospital mortality rate, functional independence at hospital discharge, duration of mechanical ventilation, hospital length of stay, and hospital cost. Multivariable regression with robust variance was used to estimate the adjusted differences in the main outcome measures between patient groups. The models were adjusted for patient age, severity of injury, and pathological features seen on head CT scan at admission.
RESULTS: On average, patients who underwent ICP/PbO(2) monitoring were younger and had more severe injuries than patients who received ICP monitoring alone. Relatively more patients treated with PbO(2) monitoring received osmotic therapy, vasopressors, and prolonged sedation. After adjustment for baseline characteristics, the hospital mortality rate was, if anything, slightly higher in patients undergoing PbO(2)-guided management than in patients monitored with ICP only (adjusted mortality difference 4.4%, 95% CI -3.9 to 13%). Patients who underwent PbO(2)-guided management also had lower adjusted functional independence scores at hospital discharge (adjusted score difference -0.75, 95% CI -1.41 to -0.09). There was a 27% relative increase (95% CI 6-53%) in the median hospital length of stay when the PbO(2) group was compared with the ICP-only group.
CONCLUSIONS: The mortality rate in patients with traumatic brain injury whose clinical management was guided by PbO(2) monitoring was not reduced in comparison with that in patients who received ICP monitoring alone. Brain tissue oxygen monitoring was associated with worse neurological outcome and increased hospital resource utilization.

PMID 19392603  J Neurosurg. 2009 Oct;111(4):644-9. doi: 10.3171/2009.2・・・
著者: R K Narayan, R P Greenberg, J D Miller, G G Enas, S C Choi, P R Kishore, J B Selhorst, H A Lutz, D P Becker
雑誌名: J Neurosurg. 1981 Jun;54(6):751-62. doi: 10.3171/jns.1981.54.6.0751.
Abstract/Text An analysis of clinical signs, singly or in combination, multimodality evoked potentials (MEP's), computerized tomography scans, and intracranial pressure (ICP) data was undertaken prospectively in 133 severely head-injured patients to ascertain the accuracy, reliability, and relative value of these indicants individually, or in various combinations, in predicting one of two categories of outcome. Erroneous predictions, either falsely optimistic (FO) or falsely pessimistic (FP), were analyzed to gain pathophysiological insights into the disease process. Falsely optimistic predictions occurred because of unpredictable complications, whereas FP predictions were due to intrinsic weakness of the indicants as prognosticators. A combination of clinical data, including age, Glasgow Coma Scale (GCS) score, pupillary response, presence of surgical mass lesions, extraocular motility, and motor posturing predicted outcome with 82% accuracy, 43% with over 90% confidence. Nine percent of predictions were FO and 9% FP. The GCS score alone was accurate in 80% of predictions, but at a lower level of confidence (25% at the over-90% level), with 7% FO and 13% FP. Computerized tomography and ICP data in isolation proved to be poor prognostic indicants. When combined individually with clinical data, however, they increased the number of predictions made with over 90% confidence to 52% and 55%, respectively. Data from MEP's represented the most accurate single prognostic indicant, with 91% correct predictions, 25% at the over-90% confidence level. There were no FP errors associated with this indicant. Supplementation of the clinical examination with MEP data yielded optimal prognostic power, an 89% accuracy rate, with 64% over the 90% confidence level and only 4% FP errors. The clinical examination remains the strongest basis for prognosticating outcome in severe head injury, but additional studies enhance the reliability of such predictions.

PMID 7241184  J Neurosurg. 1981 Jun;54(6):751-62. doi: 10.3171/jns.19・・・
著者: F Servadei, V Antonelli, G Giuliani, E Fainardi, A Chieregato, L Targa
雑誌名: Acta Neurochir Suppl. 2002;81:81-2.
Abstract/Text We have consecutively studied 110 patients with traumatic subarachnoid hemorrhage (tSAH) on the first Computed Tomography (CT) scan (obtained in each case within 3 hours from injury). The only exclusion criteria were brain death on admission, and severe hypotension due to extracranial injuries. All CTs were reviewed by one of us and the "worst" CT examination was determined. We defined the worst CT examination as that showing the most extensive degree of parenchymal-associated damage. Intracranial pressure was monitored in 25 severely head injured patients. Seventy-four patients (66%) showed an evolution from the initial CT scan (worst CT not corresponding to the admission CT). The outcome was favorable in 53 cases (73%) of patients with evolving lesions and in 32 cases (89%) with non evolving lesion. In the 25 severely head injured patients, Intra-cranial Pressure (ICP) monitoring (in combination with scheduled repeat CT scan) was helpful to identify the timing of the worst parenchymal damage and of surgery in those patients with an initial normal intracranial pressure in spite of an evolving lesion.

PMID 12168364  Acta Neurochir Suppl. 2002;81:81-2.
著者: T G Saul, T B Ducker
雑誌名: J Neurosurg. 1982 Apr;56(4):498-503. doi: 10.3171/jns.1982.56.4.0498.
Abstract/Text During 1977-1978, 127 patients with severe head injury were admitted and underwent intracranial pressure (ICP) monitoring. All patients had Glasgow Coma Scale (GCS) scores of 7 or less. All received identical initial treatment according to a standardized protocol. The patients' average age was 29 years; 60% had multiple trauma, and 35% needed emergency intracranial operations. Treatment for elevations of ICP was begun when ICP rose to 20 to 25 mm Hg, and included mannitol therapy and drainage of cerebrospinal fluid (CSF) when possible. Forty-three patients (34%) had ICP greater than or equal to 25 mm Hg; of these, 36 (84%) died. The mortality rate of the entire group was 46%. During 1979-1980, 106 patients with severe head injury were admitted and underwent ICP monitoring. Their average ager was 29 years; 51% had multiple trauma, and 31% underwent emergency intracranial surgery. All patients received the same standardized protocol as the previous series, with the exception of the treatment of ICP. In this present series: if ICP was 15 mm Hg or less (normal ICP), patients were continued on hyperventilation, steroids, and intensive care; if ICP was 16 to 24 mm Hg, mannitol was administered and CSF was drained; if ICP was 25 mm Hg or greater, the patients were randomized into a controlled barbiturate therapy study. Twenty-six patients (25%) had ICP's of 25 mm Hg or greater, compared to 34% in the previous series (p less than 0.05), and 18 of these 26 patients (69%) died. The overall mortality for this current series was 28% compared to 46% in the previous series (p less than 0.0005). This study reconfirms the high mortality rate if ICP is 25 mm Hg or greater; however, the data also document that early aggressive treatment based on ICP monitoring significantly lessens the incidence of ICP of 25 mm Hg or greater and reduces the overall mortality rate of severe head injury.

PMID 6801218  J Neurosurg. 1982 Apr;56(4):498-503. doi: 10.3171/jns.1・・・
著者: Michael Chourdakis, Michaela M Kraus, Thrasivoulos Tzellos, Chrysanthi Sardeli, Maria Peftoulidou, Dimitrios Vassilakos, Dimitrios Kouvelas
雑誌名: JPEN J Parenter Enteral Nutr. 2012 Jan;36(1):108-16. doi: 10.1177/0148607110397878. Epub 2011 Sep 30.
Abstract/Text BACKGROUND: Traumatic brain injury (TBI) results in a hypermetabolic and hypercatabolic status in which adequate nutrition support is essential to improve clinical outcome. The endocrine system of a patient with TBI is also affected and may play a critical role in either the metabolic or the immunologic response to the trauma. In the present study, the effect of standard, delayed enteral feeding (DEF), compared with early (within 24-48 hours) enteral feeding (EEF), on the endocrine function of patients with TBI was investigated.
METHODS: This comparative, prospective, open-labeled, randomized study included TBI patients admitted to the intensive care unit (ICU). Injury severity was assessed by the Glasgow Coma Scale and predicted mortality by the Acute Physiology and Chronic Health Evaluation II. Twenty-five patients received DEF and 34 patients received EEF. The effect of the onset of nutrition on pituitary, thyroidal, gonadal, and adrenal function was investigated on days 6 and 12 after admission to the hospital.
RESULTS: Levels of thyroid-stimulating hormone, free triiodothyronine, free thyroxine, and testosterone (in males) of DEF patients declined in comparison to levels of the day of admission to the ICU. The decrease of hormonal values was less pronounced in the EEF group. Cortisol concentrations rose in the DEF group; a lesser hormonal change was found in the EEF group. Deaths during the study for the DEF group and EEF group were 2 and 3, respectively.
CONCLUSIONS: EEF may exert beneficial effects on the hormonal profile of TBI patients, possibly contributing to a better clinical outcome in this patient group.

PMID 21965459  JPEN J Parenter Enteral Nutr. 2012 Jan;36(1):108-16. do・・・
著者: Roger Härtl, Linda M Gerber, Quanhong Ni, Jamshid Ghajar
雑誌名: J Neurosurg. 2008 Jul;109(1):50-6. doi: 10.3171/JNS/2008/109/7/0050.
Abstract/Text OBJECT: Traumatic brain injury (TBI) remains a serious public health crisis requiring continuous improvement in pre-hospital and inhospital care. This condition results in a hypermetabolic state that increases systemic and cerebral energy requirements, but achieving adequate nutrition to meet this demand has not been a priority in reducing death due to TBI. The effect of timing and quantity of nutrition on death within the first 2 weeks of injury was analyzed in a large prospective database of adult patients with severe TBI in New York State.
METHODS: The study is based on 797 patients with severe TBI (Glasgow Coma Scale [GCS] score < 9) treated at 22 trauma centers enrolled in a New York State quality improvement program between 2000 and 2006. The inhospital section of the prospectively collected database includes information on age, initial GCS score, weight and height, results of CT scanning, and daily parameters such as pupillary status, arterial hypotension, GCS score, and number of calories fed per day.
RESULTS: Patients who were not fed within 5 and 7 days after TBI had a 2- and 4-fold increased likelihood of death, respectively. The amount of nutrition in the first 5 days was related to death; every 10-kcal/kg decrease in caloric intake was associated with a 30-40% increase in mortality rates. This held up even after controlling for factors known to affect mortality, including arterial hypotension, age, pupillary status, initial GCS score, and CT scan findings.
CONCLUSIONS: Nutrition is a significant predictor of death due to TBI. Together with prevention of arterial hypotension, hypoxia, and intracranial hypertension it is one of the few therapeutic interventions that can directly affect TBI outcome.

PMID 18590432  J Neurosurg. 2008 Jul;109(1):50-6. doi: 10.3171/JNS/200・・・
著者: Didier Lepelletier, Antoine Roquilly, Dominique Demeure dit latte, Pierre Joachim Mahe, Olivier Loutrel, Philippe Champin, Stéphane Corvec, Edouard Naux, Michel Pinaud, Corinne Lejus, Karim Asehnoune
雑誌名: J Neurosurg Anesthesiol. 2010 Jan;22(1):32-7. doi: 10.1097/ANA.0b013e3181bdf52f.
Abstract/Text BACKGROUND: Early-onset ventilator associated pneumonia (EOVAP) are frequent in head-trauma patients, but specific risk factors are poorly studied in this population.
METHODS: We conducted a retrospective cohort study in a surgical intensive care unit. Consecutive severe head-trauma patients admitted from January 2000 to December 2002 were studied. Microorganisms, and risks factors for EOVAP were analyzed.
RESULTS: During the 3-year period, 161 patients were studied; 21.1% of them developed an EOVAP. On univariate analysis 6 variables were associated with EOVAP: early enteral feeding, barbiturate use, immunosuppression, mean Simplified Acute Physiology Score 2, acute respiratory distress syndrome, and initial neurosurgery procedures. On multivariate analysis, enteral feeding >2000 Kcal before day 5 [odds ratio (OR): 0.33, 95% confidence interval (CI): 0.21-0.85] and initial neurosurgical procedure (OR: 0.36, 95% CI: 0.15-0.89) remained protective factors for EOVAP, whereas immunosuppression (OR: 7.15, 95% CI: 1.66-30.73) and barbiturate use (OR: 2.68, 95% CI: 1.06-6.80) remained risk factors for EOVAP. EOVAP was also significantly associated with a longer duration of mechanical ventilation (14.0 vs. 11.0 d, P=0.024), and a longer sedation duration (8.3 vs. 5.8 d P=0.005). Methicillin-susceptible Staphylococcus aureus was the most common pathogen involved in EOVAP (46%).
CONCLUSIONS: We demonstrate for the first time that early enteral feeding is a protective factor for EOVAP, and this result could have clinical implications for the prevention of EOVAP after traumatic brain injury. This study also confirms that barbiturate use is an important risk factor of EOVAP whereas Methicillin-susceptible S. aureus was found to be the main pathogen involved in EOVAP.

PMID 20027012  J Neurosurg Anesthesiol. 2010 Jan;22(1):32-7. doi: 10.1・・・
著者: Jose Acosta-Escribano, Miguel Fernández-Vivas, Teodoro Grau Carmona, Juan Caturla-Such, Miguel Garcia-Martinez, Ainhoa Menendez-Mainer, Manuel Solera-Suarez, José Sanchez-Payá
雑誌名: Intensive Care Med. 2010 Sep;36(9):1532-9. doi: 10.1007/s00134-010-1908-3. Epub 2010 May 22.
Abstract/Text PURPOSE: To evaluate the efficacy of transpyloric feeding (TPF) compared with gastric feeding (GF) with regard to the incidence of ventilator-associated pneumonia in severe traumatic brain injury patients (TBI).
DESIGN AND SETTING: Prospective, open-label, randomized study in an intensive care unit of a university hospital.
PATIENTS: One hundred and four CHI adult patients admitted for TBI between April 2007 and December 2008. Patients were included within the first 24 h after ICU admission and were followed until discharge or 30 days after admission.
INTERVENTION: Patients were randomized to TPF or GF groups. They received the same diet, with 25 kcal kg(-1) day(-1) of calculated energy requirements and a nitrogen intake of 0.2 g N kg(-1) day(-1). Primary outcome was the incidence of early and ventilatory-associated pneumonia. Secondary outcomes were enteral nutrition-related gastrointestinal complications (GIC), days on mechanical ventilation, length of ICU stay and hospital stay, and sequential organ failure assessment score (SOFA).
RESULTS: The TPF group had a lower incidence of pneumonia, OR 0.3 (95% CI 0.1-0.7, P = 0.01). There were no significant differences in other nosocomial infections. The TPF group received higher amounts of diet compared to the GF group (92 vs. 84%, P < 0.01) and had lesser incidence of increased gastric residuals, OR 0.2 (95% CI 0.04-0.6, P = 0.003).
CONCLUSIONS: Enteral nutrition delivered through the transpyloric route reduces the incidence of overall and late pneumonia and improves nutritional efficacy in severe TBI patients.

PMID 20495781  Intensive Care Med. 2010 Sep;36(9):1532-9. doi: 10.1007・・・
著者: R P Rapp, B Young, D Twyman, B A Bivins, D Haack, P A Tibbs, J R Bean
雑誌名: J Neurosurg. 1983 Jun;58(6):906-12. doi: 10.3171/jns.1983.58.6.0906.
Abstract/Text This prospective randomized controlled clinical trial compares the effects of early parenteral nutrition and traditional delayed enteral nutrition upon the outcome of head-injured patients. Thirty-eight head-injured patients were randomly assigned to receive total parenteral nutrition (TPN) or standard enteral nutrition (SEN). Clinical and nutritional data were collected on all patients until death or for 18 days of hospitalization. Survival and functional recovery were monitored in survivors for 1 year. Of the 38 patients, 18 were randomized to the SEN group and 20 to the TPN group. Demographically, the two groups of patients were similar on admission. There was no significant difference in the severity of head injury between the two groups as measured by the Glasgow Coma Scale (p = 0.52). The outcome for the two groups was quite different, with eight of the 18 SEN patients dying within 18 days of injury, whereas no patient in the TPN group died within this period (p less than 0.0001). The basis for the improved survival in the TPN patients appears to be improved nutrition. The TPN patients had a more positive nitrogen balance (p less than 0.06), and a higher serum albumin level and total lymphocyte count. More adequate nutritional status may have improved the patients' immunocompetence, resulting in decreased susceptibility to sepsis. The data from this study strongly support the favorable effect of early TPN on survival from head injury.

PMID 6406649  J Neurosurg. 1983 Jun;58(6):906-12. doi: 10.3171/jns.19・・・
著者: Kenji Inaba, Jay Menaker, Bernardino C Branco, Jonathan Gooch, Obi T Okoye, Joe Herrold, Thomas M Scalea, Joseph Dubose, Demetrios Demetriades
雑誌名: J Trauma Acute Care Surg. 2013 Mar;74(3):766-71; discussion 771-3. doi: 10.1097/TA.0b013e3182826e84.
Abstract/Text BACKGROUND: Brain Trauma Foundation guidelines recommend seizure prophylaxis for preventing early posttraumatic seizure (PTS). Phenytoin (PHE) is commonly used. Despite a paucity of data in traumatic brain injury, levetiracetam (LEV) has been introduced as a potential replacement, which is more costly but does not require serum monitoring. The purpose of this study was to compare the efficacy of PHE with that of LEV for preventing early PTS.
METHODS: Consecutive blunt traumatic brain injury patients undergoing seizure prophylaxis were prospectively enrolled at two Level 1 trauma centers during a 33-month period. Seizure prophylaxis was administered according to local protocol. Patients were monitored prospectively throughout their hospital stay for clinical evidence of seizure activity. PHE was compared with LEV with clinical early PTS as the primary outcome measure, defined as a seizure diagnosed clinically, occurring within 7 days of admission.
RESULTS: A total of 1,191 patients were screened for enrollment, after excluding 378 (31.7%) who did not meet inclusion criteria; 813 (68.3%) were analyzed (406 LEV and 407 PHE). There were no significant differences between LEV and PHE in age (51.7 [21.3] vs. 53.6 [22.5], p = 0.205), male (73.9% vs. 68.8%, p = 0.108), Injury Severity Score (ISS) (20.0 [10.0] vs. 21.0 [10.6], p = 0.175), Marshall score of 3 or greater (18.5% vs. 14.7%, p = 0.153), or craniectomy (8.4% vs. 11.8%, p = 0.106). There was no difference in seizure rate (1.5% vs.1.5%, p = 0.997), adverse drug reactions (7.9% vs. 10.3%, p = 0.227), or mortality (5.4% vs. 3.7%, p = 0.236).
CONCLUSION: In this prospective evaluation of early PTS prophylaxis, LEV did not outperform PHE. Cost and need for serum monitoring should be considered in guiding the choice of prophylactic agent.
LEVEL OF EVIDENCE: Therapeutic study, level III.

PMID 23425733  J Trauma Acute Care Surg. 2013 Mar;74(3):766-71; discus・・・
著者: S S Dikmen, J E Machamer, H R Winn, G D Anderson, N R Temkin
雑誌名: Neurology. 2000 Feb 22;54(4):895-902.
Abstract/Text OBJECTIVES: To examine the neuropsychological side effects of valproate (VPA) given to prevent posttraumatic seizures.
METHODS: In a randomized, double-masked, parallel group clinical trial, we compared the seizure prevention and neuropsychological effects of 1 or 6 months of VPA to 1 week of phenytoin. We studied 279 adult subjects who were randomized within 24 hours of injury and examined with a battery of neuropsychological measures at 1, 6, and 12 months after injury. We examined drug effects cross-sectionally at 1, 6, and 12 months and longitudinally by examining differential change from 1 to 6 months and from 6 to 12 months as a function of protocol-dictated changes in treatment.
RESULTS: No significant adverse or beneficial neuropsychological effects of VPA were detected.
CONCLUSIONS: Valproate (VPA) appears to have a benign neuropsychological side effects profile, making it a cognitively safe antiepileptic drug to use for controlling established seizures or stabilizing mood. However, based on this study, VPA should not be used for prophylaxis of posttraumatic seizures because it does not prevent posttraumatic seizures, there was a trend toward more deaths in the VPA groups, and it did not have positive effects on cognition.

PMID 10690983  Neurology. 2000 Feb 22;54(4):895-902.
著者: N R Temkin, S S Dikmen, A J Wilensky, J Keihm, S Chabal, H R Winn
雑誌名: N Engl J Med. 1990 Aug 23;323(8):497-502. doi: 10.1056/NEJM199008233230801.
Abstract/Text BACKGROUND: Antiepileptic drugs are commonly used to prevent seizures that may follow head trauma. However, previous controlled studies of this practice have been inconclusive.
METHODS: To study further the effectiveness of phenytoin (Dilantin) in preventing post-traumatic seizures, we randomly assigned 404 eligible patients with serious head trauma to treatment with phenytoin (n = 208) or placebo (n = 196) for one year in a double-blind fashion. An intravenous loading dose was given within 24 hours of injury. Serum levels of phenytoin were maintained in the high therapeutic range (3 to 6 mumol of free phenytoin per liter). Follow-up was continued for two years. The primary data analysis was performed according to the intention to treat.
RESULTS: Between drug loading and day 7, 3.6 percent of the patients assigned to phenytoin had seizures, as compared with 14.2 percent of patients assigned to placebo (P less than 0.001; risk ratio, 0.27; 95 percent confidence interval, 0.12 to 0.62). Between day 8 and the end of year 1, 21.5 percent of the phenytoin group and 15.7 percent of the placebo group had seizures; at the end of year 2, the rates were 27.5 percent and 21.1 percent, respectively (P greater than 0.2 for each comparison; risk ratio, 1.20; 95 percent confidence interval, 0.71 to 2.02). This lack of a late effect could not be attributed to differential mortality, low phenytoin levels, or treatment of some early seizures in patients assigned to the placebo group.
CONCLUSIONS: Phenytoin exerts a beneficial effect by reducing seizures only during the first week after severe head injury.

PMID 2115976  N Engl J Med. 1990 Aug 23;323(8):497-502. doi: 10.1056/・・・
著者: N R Temkin, S S Dikmen, G D Anderson, A J Wilensky, M D Holmes, W Cohen, D W Newell, P Nelson, A Awan, H R Winn
雑誌名: J Neurosurg. 1999 Oct;91(4):593-600. doi: 10.3171/jns.1999.91.4.0593.
Abstract/Text OBJECT: Seizures frequently accompany moderate to severe traumatic brain injury. Phenytoin and carbamazepine are effective in preventing early, but not late, posttraumatic seizures. In this study the authors compare the safety and effectiveness of valproate with those of short-term phenytoin for prevention of seizures following traumatic brain injury.
METHODS: The study was a randomized, double-blind, single-center, parallel-group clinical trial. Treatment began within 24 hours of injury. One hundred thirty-two patients at high risk for seizures were assigned to receive a 1-week course of phenytoin, 120 were assigned to receive a 1-month course of valproate, and 127 were assigned to receive a 6-month course of valproate. The cases were followed for up to 2 years. The rates of early seizures were low and similar when using either valproate or phenytoin (1.5% in the phenytoin treatment group and 4.5% in the valproate arms of the study; p = 0.14, relative risk [RR] = 2.9, 95% confidence interval [CI] 0.7-13.3). The rates of late seizures did not differ among treatment groups (15% in patients receiving the 1-week course of phenytoin, 16% in patients receiving the 1-month course of valproate, and 24% in those receiving the 6-month course of valproate; p = 0.19, RR = 1.4, 95% CI 0.8-2.4). The rates of mortality were not significantly different between treatment groups, but there was a trend toward a higher mortality rate in patients treated with valproate (7.2% in patients receiving phenytoin and 13.4% in those receiving valproate; p = 0.07, RR = 2.0, 95% CI 0.9-4.1). The incidence of serious adverse events, including coagulation problems and liver abnormalities, was similar in phenytoin- and valproate-treated patients.
CONCLUSIONS: Valproate therapy shows no benefit over short-term phenytoin therapy for prevention of early seizures and neither treatment prevents late seizures. There was a trend toward a higher mortality rate among valproate-treated patients. The lack of additional benefit and the potentially higher mortality rate suggest that valproate should not be routinely used for the prevention of posttraumatic seizures.

PMID 10507380  J Neurosurg. 1999 Oct;91(4):593-600. doi: 10.3171/jns.1・・・
著者: S Manaka
雑誌名: Jpn J Psychiatry Neurol. 1992 Jun;46(2):311-5.
Abstract/Text
PMID 1434154  Jpn J Psychiatry Neurol. 1992 Jun;46(2):311-5.
著者: J P Muizelaar, A Marmarou, J D Ward, H A Kontos, S C Choi, D P Becker, H Gruemer, H F Young
雑誌名: J Neurosurg. 1991 Nov;75(5):731-9. doi: 10.3171/jns.1991.75.5.0731.
Abstract/Text There is still controversy over whether or not patients should be hyperventilated after traumatic brain injury, and a randomized trial has never been conducted. The theoretical advantages of hyperventilation are cerebral vasoconstriction for intracranial pressure (ICP) control and reversal of brain and cerebrospinal fluid (CSF) acidosis. Possible disadvantages include cerebral vasoconstriction to such an extent that cerebral ischemia ensues, and only a short-lived effect on CSF pH with a loss of HCO3-buffer from CSF. The latter disadvantage might be overcome by the addition of the buffer tromethamine (THAM), which has shown some promise in experimental and clinical use. Accordingly, a trial was performed with patients randomly assigned to receive normal ventilation (PaCO2 35 +/- 2 mm Hg (mean +/- standard deviation): control group), hyperventilation (PaCO2 25 +/- 2 mm Hg: HV group), or hyperventilation plus THAM (PaCO2 25 +/- 2 mm Hg: HV + THAM group). Stratification into subgroups of patients with motor scores of 1-3 and 4-5 took place. Outcome was assessed according to the Glasgow Outcome Scale at 3, 6, and 12 months. There were 41 patients in the control group, 36 in the HV group, and 36 in the HV + THAM group. The mean Glasgow Coma Scale score for each group was 5.7 +/- 1.7, 5.6 +/- 1.7, and 5.9 +/- 1.7, respectively; this score and other indicators of severity of injury were not significantly different. A 100% follow-up review was obtained. At 3 and 6 months after injury the number of patients with a favorable outcome (good or moderately disabled) was significantly (p less than 0.05) lower in the hyperventilated patients than in the control and HV + THAM groups. This occurred only in patients with a motor score of 4-5. At 12 months posttrauma this difference was not significant (p = 0.13). Biochemical data indicated that hyperventilation could not sustain alkalinization in the CSF, although THAM could. Accordingly, cerebral blood flow (CBF) was lower in the HV + THAM group than in the control and HV groups, but neither CBF nor arteriovenous difference of oxygen data indicated the occurrence of cerebral ischemia in any of the three groups. Although mean ICP could be kept well below 25 mm Hg in all three groups, the course of ICP was most stable in the HV + THAM group. It is concluded that prophylactic hyperventilation is deleterious in head-injured patients with motor scores of 4-5.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID 1919695  J Neurosurg. 1991 Nov;75(5):731-9. doi: 10.3171/jns.199・・・
著者: P R Cooper, S Moody, W K Clark, J Kirkpatrick, K Maravilla, A L Gould, W Drane
雑誌名: J Neurosurg. 1979 Sep;51(3):307-16. doi: 10.3171/jns.1979.51.3.0307.
Abstract/Text A prospective double-blind study of the effects of dexamethasone administration on the outcome of patients with severe head injuries was performed. Patients were stratified for severity of neurological injury and were treated with placebo, low-dose dexamethasone (16 mg/day), or high-dose dexamethasone (96 mg/day) for a period of 6 days. Outcome was evaluated at 6 months following injury. Of the 76 patients available for analysis, a good outcome was achieved in 37% of placebo-treated patients, 44% of low-dose-treated patients, and 29% of high-dose-treated patients. These differences are not statistically significant. Similarly dexamethasone administration had no statistically significant effect on intracranial pressure patterns or serial neurological examinations during hospitalization. Gastrointestinal bleeding occurred in only one patient. Good outcome was associated with age under 10 years, lighter depth of coma on admission, and the preservation of brain-stem reflexes upon admission. A recalculation of data in previous clinical series purporting to show an improvement in outcome as a result of corticosteroid therapy shows no significant difference in outcome when steroid- and placebo-treated patients are compared. In our series, 90% of all deaths were caused by recurrent intracranial hematomas, medical complications, or diffuse brain injuries with parenchymal hemorrhage and tissue disruption -- causes of death which cannot be affected by corticosteroid therapy. The study suggests that dexamethasone in either high or low dosages has no significant effect on morbidity and mortality following severe head injury.

PMID 381599  J Neurosurg. 1979 Sep;51(3):307-16. doi: 10.3171/jns.19・・・
著者: T G Saul, T B Ducker, M Salcman, E Carro
雑誌名: J Neurosurg. 1981 May;54(5):596-600. doi: 10.3171/jns.1981.54.5.0596.
Abstract/Text This is a prospective randomized study of the efficacy of steroid therapy in patients with severe head injury. One hundred patients were randomized into two equal groups: the steroid group received 5 mg/kg/day of methylprednisolone, and the nonsteroid group received no drug. The groups were similar in their clinical features. All patients received a standardized therapeutic regimen. The patients were also classified as early responders or nonresponders to the overall treatment protocol without regard to steroid administration, on the basis of change in Glasgow Coma Scale score during the first 3 days of admission. There was no statistically significant difference in the outcome of the steroid and nonsteroid group at 6 months. Of the responders who were on steroids, 74% had good outcomes or were disabled, compared with 56% of the responders who did not receive steroids. In the nonresponder group, the patients on steroids were actually associated with a worse outcome than those who did not receive steroids: 75% of the nonresponders who received steroids were dead or vegetative, compared to 56% of those who were not receiving steroids. The data suggest that: 1) the effect of steroids may be different for different patient groups; 2) in order to identify these patients, a sensitive coma scale is needed; and 3) a rational approach to steroid therapy in head-injured patients may be to start all patients on steroids, but to discontinue their use in patients identified as not benefiting from steroid therapy.

PMID 7014790  J Neurosurg. 1981 May;54(5):596-600. doi: 10.3171/jns.1・・・
著者: S L Giannotta, M H Weiss, M L Apuzzo, E Martin
雑誌名: Neurosurgery. 1984 Oct;15(4):497-501.
Abstract/Text Eighty-eight patients with a Glasgow coma score of 8 or less 6 hours after nonpenetrating head trauma were given either high dose methylprednisolone sodium succinate (30 mg/kg q6h X2, then 250 mg q6h X6, then tapering over 8 days), low dose methylprednisolone (1.5 mg/kg q6h X2, then 25 mg q6h X6, then tapering over 8 days), or placebo. Standard care including the removal of traumatic hematomas, assisted ventilation, and intracranial pressure monitoring and control was carried out. Follow-up assessments were performed on all surviving patients at 6 months and were graded according to the Glascow outcome scale. No statistically significant difference in outcome was seen between the low dose group and the placebo group. The high dose group experienced a mortality of 39% as compared to a 52% mortality in the low dose and placebo groups (P less than 0.05). Mortality differences were most marked in patients less than 40 years old, with the high dose group experiencing a mortality of 6% as compared to a 43% mortality for the low dose and placebo groups (P less than 0.05). For patients under 50 years old, the incidence of recovery of speech was 62% compared to 36% in the low dose and placebo groups (P less than 0.5). The increased survival in those treated with high dose corticoids, however, was associated with an increase in the poorer outcome categories.

PMID 6333649  Neurosurgery. 1984 Oct;15(4):497-501.
著者: M R Gaab, H A Trost, A Alcantara, A Karimi-Nejad, D Moskopp, R Schultheiss, W J Bock, J Piek, H Klinge, F Scheil
雑誌名: Zentralbl Neurochir. 1994;55(3):135-43.
Abstract/Text In a prospective randomized double-blind multicenter trial, the efficacy and safety of a 51-hour ultra-high intravenous dexamethasone dosing regimen was investigated in patients with moderate and severe head injury. 300 patients between 15 and 55 years of age were randomized to receive either placebo or dexamethasone: 500 mg intravenous infusion within 3 h after trauma initially, followed by 200 mg after 3 h, thereafter 8 times 200 mg at 6 hourly intervals, resulting in a total administered dose of 2,3 g in 51 hours. Primary end points for assessment of efficacy were: Modified Glasgow Coma Scale (grading 3-16) on Day 5, modified Glasgow Outcome Scale (grading 1-6) 10-14 months after injury, and the time interval until consciousness improved above a level of modified GCS > or = 8. Secondary endpoints were CT results and neurological and laboratory data. The two groups were well matched with respect to important prognostic variables, such as age, severity of trauma, and interval between trauma and application of the drug. 269 patients (89.7%) were available for final examination after 10-14 months. Results were surprisingly favourable in both groups: Lethality in the dexamethasone and placebo group was 14.3 and 15.4%, respectively, and 61.7 and 57.4%, respectively, achieved social and professional rehabilitation after 10-14 months (outcome scale 6). No statistical difference was seen between the dexamethasone and the placebo group in any of the primary end points of efficacy and safety (incidence of upper gastrointestinal bleeding, infection, and thrombosis).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID 7810251  Zentralbl Neurochir. 1994;55(3):135-43.
著者: L F Marshall, A I Maas, S B Marshall, A Bricolo, M Fearnside, F Iannotti, M R Klauber, J Lagarrigue, R Lobato, L Persson, J D Pickard, J Piek, F Servadei, G N Wellis, G F Morris, E D Means, B Musch
雑誌名: J Neurosurg. 1998 Oct;89(4):519-25. doi: 10.3171/jns.1998.89.4.0519.
Abstract/Text OBJECT: The authors prospectively studied the efficacy of tirilazad mesylate, a novel aminosteroid, in humans with head injuries.
METHODS: A cohort of 1120 head-injured patients received at least one dose of study medication (tirilazad or placebo). Eighty-five percent (957) of the patients had suffered a severe head injury (Glasgow Coma Scale [GCS] score 4-8) and 15% (163) had sustained a moderate head injury (GCS score 9-12). Six-month outcomes for the tirilazad- and placebo-treated groups for the Glasgow Outcome Scale categories of both good recovery and death showed no significant difference (good recovery in the tirilazad-treated group was 39% compared with the placebo group in which it was 42% [p=0.461]; death in the tirilazad-treated group occurred in 26% of patients compared with the placebo group, in which it occurred in 25% [p=0.750]). Subgroup analysis suggested that tirilazad mesylate may be effective in reducing mortality rates in males suffering from severe head injury with accompanying traumatic subarachnoid hemorrhage (death in the tirilazad-treated group occurred in 34% of patients; in the placebo group it occurred in 43% [p=0.026]). No significant differences in frequency or types of serious adverse events were shown between the treatment and placebo groups.
CONCLUSIONS: Striking problems with imbalance concerning basic prognostic variables were observed in spite of the large population studied. These imbalances concerned pretreatment hypotension, pretreatment hypoxia, and the incidence of epidural hematomas. In future trials of pharmacological therapy for severe head injury, serious consideration must be given to alternative randomization strategies. Given the heterogeneous nature of head injury and the identification of populations that do relatively well with standard therapy, target populations with a higher risk for mortality and morbidity may be more suitable for clinical trials of such agents.

PMID 9761043  J Neurosurg. 1998 Oct;89(4):519-25. doi: 10.3171/jns.19・・・
著者: N F Kassell, E C Haley, C Apperson-Hansen, W M Alves
雑誌名: J Neurosurg. 1996 Feb;84(2):221-8. doi: 10.3171/jns.1996.84.2.0221.
Abstract/Text Tirilazad mesylate, a nonglucocorticoid 21-aminosteroid, has been shown in experimental models to reduce vasospasm following subarachnoid hemorrhage (SAH) and to reduce infarct size from focal cerebral ischemia. To test whether treatment with tirilazad would reduce ischemic symptoms from vasospasm and improve overall outcome in patients with ruptured aneurysms, a prospective randomized, double-blind, vehicle-controlled trial was conducted at 41 neurosurgical centers in Europe, Australia, and New Zealand. One thousand twenty-three patients were randomly assigned to receive 0.6, 2, or 6 mg/kg per day of intravenously administered tirilazad or a placebo containing the citrate vehicle. All patients were also treated with intravenously administered nimodipine. Patients receiving 6 mg/kg per day of tirilazad had reduced mortality (p = 0.01) and a greater frequency of good recovery on the Glasgow Outcome Scale 3 months after SAH (p = 0.01) than similar patients treated with vehicle. There was a reduction in symptomatic vasospasm in the group that received 6 mg/kg per day tirilazad; however, the difference was not statistically significant (p = 0.048). The benefits of treatment with tirilazad were predominantly shown in men rather than in women. There were no material differences between the outcomes in the groups treated with 0.6 and 2 mg/kg tirilazad per day and the group treated with vehicle. Tirilazad was well tolerated at all three dose levels. These observations suggest that tirilazad mesylate, at a dosage of 6 mg/kg per day, is safe and improves overall outcome in patients (especially in men) who have experienced an aneurysmal SAH.

PMID 8592224  J Neurosurg. 1996 Feb;84(2):221-8. doi: 10.3171/jns.199・・・
著者: P Alderson, I Roberts
雑誌名: BMJ. 1997 Jun 28;314(7098):1855-9.
Abstract/Text OBJECTIVE: To quantify the effectiveness and safety of corticosteroids in the treatment of acute traumatic brain injury.
DESIGN: Systematic review of randomised controlled trials of corticosteroids in acute traumatic brain injury. Summary odds ratios were estimated as an inverse variance weighted average of the odds ratios for each study.
SETTING: Randomised trials available by March 1996.
SUBJECTS: The included trials with outcome data comprised 2073 randomised participants.
RESULTS: The effect of corticosteroids on the risk of death was reported in 13 included trials. The pooled odds ratio for the 13 trials was 0.91 (95% confidence interval 0.74 to 1.12). Pooled absolute risk reduction was 1.8% (-2.5% to 5.7%). For the 10 trials that reported death or disability the pooled odds ratio was 0.90 (0.72 to 1.11). For infections of any type the pooled odds ratio was 0.92 (0.69 to 1.23) and for the seven trials reporting gastrointestinal bleeding it was 1.05 (0.44 to 2.52). With only those trials with the best quality of concealment of allocation, the pooled odds ratio estimates for death and death or disability became closer to unity.
CONCLUSIONS: This systematic review of randomised controlled trials of corticosteroids in acute traumatic brain injury shows that there remains considerable uncertainty over their effects. Neither moderate benefits nor moderate harmful effects can be excluded. The widely practicable nature of the drugs and the importance of the health problem suggest that large simple trials are feasible and worth while to establish whether there are any benefits from use of corticosteroids in this setting.

PMID 9224126  BMJ. 1997 Jun 28;314(7098):1855-9.
著者: Ian Roberts, David Yates, Peter Sandercock, Barbara Farrell, Jonathan Wasserberg, Gabrielle Lomas, Rowland Cottingham, Petr Svoboda, Nigel Brayley, Guy Mazairac, Véronique Laloë, Angeles Muñoz-Sánchez, Miguel Arango, Bennie Hartzenberg, Hussein Khamis, Surakrant Yutthakasemsunt, Edward Komolafe, Fatos Olldashi, Yadram Yadav, Francisco Murillo-Cabezas, Haleema Shakur, Phil Edwards, CRASH trial collaborators
雑誌名: Lancet. 2004 Oct 9-15;364(9442):1321-8. doi: 10.1016/S0140-6736(04)17188-2.
Abstract/Text BACKGROUND: Corticosteroids have been used to treat head injuries for more than 30 years. In 1997, findings of a systematic review suggested that these drugs reduce risk of death by 1-2%. The CRASH trial--a multicentre international collaboration--aimed to confirm or refute such an effect by recruiting 20000 patients. In May, 2004, the data monitoring committee disclosed the unmasked results to the steering committee, which stopped recruitment.
METHODS: 10008 adults with head injury and a Glasgow coma score (GCS) of 14 or less within 8 h of injury were randomly allocated 48 h infusion of corticosteroids (methylprednisolone) or placebo. Primary outcomes were death within 2 weeks of injury and death or disability at 6 months. Prespecified subgroup analyses were based on injury severity (GCS) at randomisation and on time from injury to randomisation. Analysis was by intention to treat. Effects on outcomes within 2 weeks of randomisation are presented in this report. This study is registered as an International Standard Randomised Controlled Trial, number ISRCTN74459797.
FINDINGS: Compared with placebo, the risk of death from all causes within 2 weeks was higher in the group allocated corticosteroids (1052 [21.1%] vs 893 [17.9%] deaths; relative risk 1.18 [95% CI 1.09-1.27]; p=0.0001). The relative increase in deaths due to corticosteroids did not differ by injury severity (p=0.22) or time since injury (p=0.05).
INTERPRETATION: Our results show there is no reduction in mortality with methylprednisolone in the 2 weeks after head injury. The cause of the rise in risk of death within 2 weeks is unclear.

PMID 15474134  Lancet. 2004 Oct 9-15;364(9442):1321-8. doi: 10.1016/S0・・・
著者: D James Cooper, Jeffrey V Rosenfeld, Lynnette Murray, Yaseen M Arabi, Andrew R Davies, Paul D'Urso, Thomas Kossmann, Jennie Ponsford, Ian Seppelt, Peter Reilly, Rory Wolfe, DECRA Trial Investigators, Australian and New Zealand Intensive Care Society Clinical Trials Group
雑誌名: N Engl J Med. 2011 Apr 21;364(16):1493-502. doi: 10.1056/NEJMoa1102077. Epub 2011 Mar 25.
Abstract/Text BACKGROUND: It is unclear whether decompressive craniectomy improves the functional outcome in patients with severe traumatic brain injury and refractory raised intracranial pressure.
METHODS: From December 2002 through April 2010, we randomly assigned 155 adults with severe diffuse traumatic brain injury and intracranial hypertension that was refractory to first-tier therapies to undergo either bifrontotemporoparietal decompressive craniectomy or standard care. The original primary outcome was an unfavorable outcome (a composite of death, vegetative state, or severe disability), as evaluated on the Extended Glasgow Outcome Scale 6 months after the injury. The final primary outcome was the score on the Extended Glasgow Outcome Scale at 6 months.
RESULTS: Patients in the craniectomy group, as compared with those in the standard-care group, had less time with intracranial pressures above the treatment threshold (P<0.001), fewer interventions for increased intracranial pressure (P<0.02 for all comparisons), and fewer days in the intensive care unit (ICU) (P<0.001). However, patients undergoing craniectomy had worse scores on the Extended Glasgow Outcome Scale than those receiving standard care (odds ratio for a worse score in the craniectomy group, 1.84; 95% confidence interval [CI], 1.05 to 3.24; P=0.03) and a greater risk of an unfavorable outcome (odds ratio, 2.21; 95% CI, 1.14 to 4.26; P=0.02). Rates of death at 6 months were similar in the craniectomy group (19%) and the standard-care group (18%).
CONCLUSIONS: In adults with severe diffuse traumatic brain injury and refractory intracranial hypertension, early bifrontotemporoparietal decompressive craniectomy decreased intracranial pressure and the length of stay in the ICU but was associated with more unfavorable outcomes. (Funded by the National Health and Medical Research Council of Australia and others; DECRA Australian Clinical Trials Registry number, ACTRN012605000009617.).

PMID 21434843  N Engl J Med. 2011 Apr 21;364(16):1493-502. doi: 10.105・・・
著者: Ji-Yao Jiang, Wei Xu, Wei-Ping Li, Wen-Hui Xu, Jun Zhang, Ying-Hui Bao, Yu-Hua Ying, Qi-Zhong Luo
雑誌名: J Neurotrauma. 2005 Jun;22(6):623-8. doi: 10.1089/neu.2005.22.623.
Abstract/Text To compare the effect of standard trauma craniectomy (STC) versus limited craniectomy (LC) on the outcome of severe traumatic brain injury (TBI) with refractory intracranial hypertension, we conducted a study at five medical centers of 486 patients with severe TBI (Glasgow Coma Scale score 0.05). The results of the study indicate that STC significantly improves outcome in severe TBI with refractory intracranial hypertension resulting from unilateral frontotemporoparietal contusion with or without intracerebral or subdural hematoma. This suggests that STC, rather than LC, be recommended for such patients.

PMID 15941372  J Neurotrauma. 2005 Jun;22(6):623-8. doi: 10.1089/neu.2・・・
著者: Wusi Qiu, Chenchen Guo, Hong Shen, Keyong Chen, Liang Wen, Hongjie Huang, Min Ding, Li Sun, Qizhou Jiang, Weiming Wang
雑誌名: Crit Care. 2009;13(6):R185. doi: 10.1186/cc8178. Epub 2009 Nov 23.
Abstract/Text INTRODUCTION: Acute post-traumatic brain swelling (BS) is one of the pathological forms that need emergent treatment following traumatic brain injury. There is controversy about the effects of craniotomy on acute post-traumatic BS. The aim of the present clinical study was to assess the efficacy of unilateral decompressive craniectomy (DC) or unilateral routine temporoparietal craniectomy on patients with unilateral acute post-traumatic BS.
METHODS: Seventy-four patients of unilateral acute post-traumatic BS with midline shifting more than 5 mm were divided randomly into two groups: unilateral DC group (n = 37) and unilateral routine temporoparietal craniectomy group (control group, n = 37). The vital signs, the intracranial pressure (ICP), the Glasgow outcome scale (GOS), the mortality rate and the complications were prospectively analysed.
RESULTS: The mean ICP values of patients in the unilateral DC group at hour 24, hour 48, hour 72 and hour 96 after injury were much lower than those of the control group (15.19 +/- 2.18 mmHg, 16.53 +/- 1.53 mmHg, 15.98 +/- 2.24 mmHg and 13.518 +/- 2.33 mmHg versus 19.95 +/- 2.24 mmHg, 18.32 +/- 1.77 mmHg, 21.05 +/- 2.23 mmHg and 17.68 +/- 1.40 mmHg, respectively). The mortality rates at 1 month after treatment were 27% in the unilateral DC group and 57% in the control group (p = 0.010). Good neurological outcome (GOS Score of 4 to 5) rates 1 year after injury for the groups were 56.8% and 32.4%, respectively (p = 0.035). The incidences of delayed intracranial hematoma and subdural effusion were 21.6% and 10.8% versus 5.4% and 0, respectively (p = 0.041 and 0.040).
CONCLUSIONS: Our data suggest that unilateral DC has superiority in lowering ICP, reducing the mortality rate and improving neurological outcomes over unilateral routine temporoparietal craniectomy. However, it increases the incidence of delayed intracranial hematomas and subdural effusion, some of which need secondary surgical intervention. These results provide information important for further large and multicenter clinical trials on the effects of DC in patients with acute post-traumatic BS.
TRIAL REGISTRATION: ISRCTN14110527.

PMID 19930556  Crit Care. 2009;13(6):R185. doi: 10.1186/cc8178. Epub 2・・・
著者: Peter J Hutchinson, Angelos G Kolias, Ivan S Timofeev, Elizabeth A Corteen, Marek Czosnyka, Jake Timothy, Ian Anderson, Diederik O Bulters, Antonio Belli, C Andrew Eynon, John Wadley, A David Mendelow, Patrick M Mitchell, Mark H Wilson, Giles Critchley, Juan Sahuquillo, Andreas Unterberg, Franco Servadei, Graham M Teasdale, John D Pickard, David K Menon, Gordon D Murray, Peter J Kirkpatrick, RESCUEicp Trial Collaborators
雑誌名: N Engl J Med. 2016 Sep 22;375(12):1119-30. doi: 10.1056/NEJMoa1605215. Epub 2016 Sep 7.
Abstract/Text BACKGROUND: The effect of decompressive craniectomy on clinical outcomes in patients with refractory traumatic intracranial hypertension remains unclear.
METHODS: From 2004 through 2014, we randomly assigned 408 patients, 10 to 65 years of age, with traumatic brain injury and refractory elevated intracranial pressure (>25 mm Hg) to undergo decompressive craniectomy or receive ongoing medical care. The primary outcome was the rating on the Extended Glasgow Outcome Scale (GOS-E) (an 8-point scale, ranging from death to "upper good recovery" [no injury-related problems]) at 6 months. The primary-outcome measure was analyzed with an ordinal method based on the proportional-odds model. If the model was rejected, that would indicate a significant difference in the GOS-E distribution, and results would be reported descriptively.
RESULTS: The GOS-E distribution differed between the two groups (P<0.001). The proportional-odds assumption was rejected, and therefore results are reported descriptively. At 6 months, the GOS-E distributions were as follows: death, 26.9% among 201 patients in the surgical group versus 48.9% among 188 patients in the medical group; vegetative state, 8.5% versus 2.1%; lower severe disability (dependent on others for care), 21.9% versus 14.4%; upper severe disability (independent at home), 15.4% versus 8.0%; moderate disability, 23.4% versus 19.7%; and good recovery, 4.0% versus 6.9%. At 12 months, the GOS-E distributions were as follows: death, 30.4% among 194 surgical patients versus 52.0% among 179 medical patients; vegetative state, 6.2% versus 1.7%; lower severe disability, 18.0% versus 14.0%; upper severe disability, 13.4% versus 3.9%; moderate disability, 22.2% versus 20.1%; and good recovery, 9.8% versus 8.4%. Surgical patients had fewer hours than medical patients with intracranial pressure above 25 mm Hg after randomization (median, 5.0 vs. 17.0 hours; P<0.001) but had a higher rate of adverse events (16.3% vs. 9.2%, P=0.03).
CONCLUSIONS: At 6 months, decompressive craniectomy in patients with traumatic brain injury and refractory intracranial hypertension resulted in lower mortality and higher rates of vegetative state, lower severe disability, and upper severe disability than medical care. The rates of moderate disability and good recovery were similar in the two groups. (Funded by the Medical Research Council and others; RESCUEicp Current Controlled Trials number, ISRCTN66202560 .).

PMID 27602507  N Engl J Med. 2016 Sep 22;375(12):1119-30. doi: 10.1056・・・
著者: Enyinna L Nwachuku, Ava M Puccio, Anita Fetzick, Bobby Scruggs, Yue-Fang Chang, Lori A Shutter, David O Okonkwo
雑誌名: Neurocrit Care. 2014 Feb;20(1):49-53. doi: 10.1007/s12028-013-9885-3.
Abstract/Text INTRODUCTION: There is clinical equipoise regarding whether neurointensive care unit management of external ventricular drains (EVD) in severe traumatic brain injury (TBI) should involve an open EVD, with continuous drainage of cerebrospinal fluid (CSF), versus a closed EVD, with intermittent opening as necessary to drain CSF. In a matched cohort design, we assessed the relative impact of continuous versus intermittent CSF drainage on intracranial pressure in the management of adult severe TBI.
METHODS: Sixty-two severe TBI patients were assessed. Thirty-one patients managed by open EVD drainage were matched by age, sex, and injury severity (initial Glasgow Coma Scale (GCS) score) to 31 patients treated with a closed EVD drainage. Patients in the open EVD group also had a parenchymal intracranial pressure (ICP) monitor placed through an adjacent burr hole, allowing real-time recording of ICP. Hourly ICP and other pertinent data, such as length of stay in intensive care unit (LOS-ICU), Injury Severity Score, and survival status, were extracted from our prospective database.
RESULTS: With age, injury severity (initial GCS score), and neurosurgical intervention adjusted for, there was a statistically significant difference of 5.66 mmHg in mean ICP (p < 0.0001) between the open and the closed EVD groups, with the closed EVD group exhibiting greater mean ICP. ICP burden (ICP ≥ 20 mmHg) was shown to be significantly higher in the intermittent EVD group (p = 0.0002) in comparison with the continuous EVD group.
CONCLUSION: Continuous CSF drainage via an open EVD seemed to be associated with more effective ICP control in the management of adult severe TBI.

PMID 23943318  Neurocrit Care. 2014 Feb;20(1):49-53. doi: 10.1007/s120・・・
著者: Donald E G Griesdale, Jonathan McEwen, Tobias Kurth, Dean R Chittock
雑誌名: Can J Neurol Sci. 2010 Jan;37(1):43-8.
Abstract/Text PURPOSE: To determine our institutional adherence to the Brain Trauma Foundation guidelines with respect to intracranial pressure (ICP) monitoring, and examine the relationship between external ventricular drain (EVD) use and mortality.
MATERIALS & METHODS: Retrospective cohort study of 171 patients with severe traumatic brain injury (TBI). Propensity score adjusted logistic regression was used to model the association between EVD use and mortality.
RESULTS: EVDs were inserted in 98 of 171 patients. Of the 73 patients without an EVD, 63 (86%) would have qualified for ICP monitoring under the current guidelines. EVDs were in situ for a median of 8 days (SD 6). In adjusted analyses, EVD use was associated with hospital mortality (OR 2.8, 95% CI: 1.1 - 7.1, p = 0.04) and 28-day mortality (OR 2.1, 95% CI: 0.80 - 5.6, p = 0.13). We observed significant modification of the association between EVD and 28-day mortality by GCS within 12 hours (p-interaction = 0.04), indicating strong association only among those patients with GCS score of at least 6 (OR 5.0, 95% CI: 1.5 - 16.7, p < 0.01).
CONCLUSIONS: The association of EVD with 28-day mortality was only apparent among patients with GCS score of > or = 6. Further research is warranted to further refine which patients may benefit from ICP monitoring.

PMID 20169772  Can J Neurol Sci. 2010 Jan;37(1):43-8.

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