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意識障害

著者: 山中俊祐 福井大学医学部附属病院 救急部

監修: 林寛之 福井大学医学部附属病院

著者校正済:2021/09/29
現在監修レビュー中
参考ガイドライン:
  1. Rogers G, O'Flynn N. NICE guideline: transient loss of consciousness(blackouts) in adults and young people. Br J Gen Pract. 2011 Jan;61(582):40-2.doi: 10.3399/bjgp11X548965. PubMed PMID: 21401989; PubMed Central PMCID:PMC3020048.
患者向け説明資料

概要・推奨   

  1. 遷延する意識障害患者で原因不明の場合、脳波検査により非けいれん性てんかんを除外することが、おそらく推奨される(推奨度2)。
  1. せん妄の診断にConfusion Assessment Method(CAM)を利用することが強く推奨される。CAMの感度は86%、特異度は100%であった(推奨度1)。
  1. 救急外来に来院する意識障害患者の原因は多様である。
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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:
山中俊祐 : 研究費・助成金など(福井県「新型コロナウイルス感染症研究推進事業」,福田記念医療技術振興財団)[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. 定期レビューを行い、鑑別疾患の追加等を行った。

病態・疫学・診察

疫学情報・病態・注意事項  
  1. 意識障害とは、意識の清明度の低下(傾眠、昏迷、半昏睡、昏睡)、または、意識内容の変化(せん妄、もうろう状態)を認める状態である。
  1. 意識障害は、特に高齢者において、救急外来受診の主原因の1つである。
  1. 意識障害という一般的用語はさまざまな同意語:混乱、器質的脳症候群、または単に「何かがおかしい」で表現されることもある。
  1. 米国の研究によると、65歳以上の救急外来を受診した患者のうち少なくとも15%は何らかの意識障害を来していた。
  1. この割合は年齢とともに上昇する。よって高齢化とともに、その罹患率は上昇すると予測される。
  1. 原因疾患は多岐にわたるが、大別すると、代謝・全身的原因と構造学的原因に分かれる。
  1. 代謝・全身的原因:
  1. 低酸素症
  1. 脳組織低還流
  1. 感染
  1. 中毒
  1. 電解質異常
  1. 代謝・内分泌異常
  1. 精神科疾患
  1. 構造学的原因:
  1. 頭部外傷
  1. 脳卒中
  1. 脳腫瘍
  1. 中枢神経感染症
  1. なお、原因疾患で最も多いのは神経疾患であった。
 
  1. 救急外来に来院する意識障害患者の原因は多様である(推奨度2)。
  1. 救急外来に来院した317例の意識障害患者の後ろ向き研究。意識障害の原因と頻度は、神経学的疾患(28%)、中毒(21%)、外傷(14%)、精神科疾患(14%)、感染症(10%)、代謝内分泌疾患(5%)、呼吸器疾患(3%)、腫瘍(3%)、循環器疾患(1%)、消化器疾患(1%)、腎疾患(1%)であった[1]
  1. また、他の研究だが、2008年のLeongらによる、単独の救急外来に来院した意識障害患者967名の前向き研究では、表のような原因疾患の頻度が示されている。
 
意識障害の原因

2008年のLeongらによる、単独の救急外来に来院した意識障害患者967名の前向き研究では、表のような原因疾患の頻度が示されている。

出典

img1:  Prospective study of patients with altered mental status: clinical features and outcome.
 
 Int J Emerg Med. 2008 Sep;1(3):179-82. d・・・
問診・診察のポイント  
  1. 意識障害患者は一般的に多くの評価を必要とする。意識障害のため病歴聴取が困難なことも多い。

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文献 

著者: William Kanich, William J Brady, J Stephen Huff, Andrew D Perron, Christopher Holstege, George Lindbeck, C Thomas Carter
雑誌名: Am J Emerg Med. 2002 Nov;20(7):613-7. doi: 10.1053/ajem.2002.35464.
Abstract/Text The purpose of this study was to determine the etiologies responsible for altered mental status (AMS) in an emergency department (ED) population, to gauge the diagnostic (DX) value of the various features of the clinical evaluation, and to examine patient outcomes. Prospective identification of patients with AMS followed by a retrospective review of the medical record was performed in a university hospital E among ED patients with AMS. Three hundred seventeen patients (5% of the ED patient volume) were identified with a mean age of 49 years (57% men). Descriptions of the AMS included 24% unresponsive, 46% lethargic/difficult to arouse, 12% agitated, and 18% unusual behavior. The most common discharge diagnoses accounting for AMS were neurologic (28%) and toxicologic (21%) followed by trauma (14%), psychiatric (14%), infectious (10%), endocrine/metabolic (5%), pulmonary (3%), oncologic (3%), cardiovascular (1%), gastrointestinal (1%), and renal (1%). The specific features of the clinical evaluation of greatest DX value followed by rates of positive DX finding included history of present event (51%), past medical history (43%), and physical examination (41%); features of little DX value included radiographs (16%), 12-lead electrocardiogram (7%), and various laboratory studies (chemistry panel [5%], complete blood count [1%], coagulation panel [0], urinalysis [11%]). Sixty-four percent of the patients were admitted with a mean hospital stay of 7.6 days and 9% deaths. Common causes of AMS included neurologic, toxicologic, traumatic, and psychiatric syndromes. The patient history and physical examination were most useful in DX terms; ancillary investigations were less often DX. This group represented a minority of the ED population yet rates of ED resource use, hospital admission, and death were high.

Copyright 2002, Elsevier Science (USA). All rights reserved.)
PMID 12442240  Am J Emerg Med. 2002 Nov;20(7):613-7. doi: 10.1053/ajem・・・
著者: J Monette, G Galbaud du Fort, S H Fung, F Massoud, Y Moride, L Arsenault, M Afilalo
雑誌名: Gen Hosp Psychiatry. 2001 Jan-Feb;23(1):20-5.
Abstract/Text The objective of this study was to compare the results of the Confusion Assessment Method (CAM) obtained by a trained non-physician interviewer to those obtained by a geriatrician, among a sample of elderly patients seen in an emergency room. A group of 110 elderly patients (> or =66 years) were evaluated in the emergency room by a lay interviewer. The geriatrician conducted an interview in the presence of the lay interviewer. Subsequently, the geriatrician and the lay interviewer completed a CAM checklist independently. Kappa statistics, sensitivity, specificity, positivity predictive value (PPV), and negative predictive value (NPV) for the geriatrician's and lay interviewer's results with the CAM diagnostic algorithm were compared. The kappa coefficient was 0.91, the sensitivity 0.86, the specificity 1.00, the PPV 1.00, and the NPV 0.97. In conclusion, the CAM used by a trained lay interviewer in the emergency room is sensitive, specific, reliable and easy to use for the identification of patients with delirium. The under-recognition and under-treatment of delirium is a major health issue and has important clinical and financial implications. The implementation of systematic screening in populations at risk could increase the rate of early detection and lead to the appropriate management of delirious patients.

PMID 11226553  Gen Hosp Psychiatry. 2001 Jan-Feb;23(1):20-5.
著者: Janus P Ong, Anjana Aggarwal, Derk Krieger, Kirk A Easley, Matthew T Karafa, Frederick Van Lente, Alejandro C Arroliga, Kevin D Mullen
雑誌名: Am J Med. 2003 Feb 15;114(3):188-93.
Abstract/Text PURPOSE: Because the correlation between ammonia levels and the severity of hepatic encephalopathy remains controversial, we prospectively evaluated the correlation in 121 consecutive patients with cirrhosis.
METHODS: The diagnosis of hepatic encephalopathy was based on clinical criteria, and the severity of hepatic encephalopathy was based on the West Haven Criteria for grading of mental status. Arterial and venous blood samples were obtained from each patient. Four types of ammonia measurements were analyzed: arterial and venous total ammonia, and arterial and venous partial pressure of ammonia. Spearman rank correlations (r(s)) were calculated.
RESULTS: Of the 121 patients, 30 (25%) had grade 0 encephalopathy (no signs or symptoms), 27 (22%) had grade 1, 23 (19%) had grade 2, 28 (23%) had grade 3, and 13 (11%) had grade 4 (the most severe signs and symptoms). Each of the four measures of ammonia increased with the severity of hepatic encephalopathy: arterial total ammonia (r(s) = 0.61, P < or = 0.001), venous total ammonia (r(s) = 0.56, P < or = 0.001), arterial partial pressure of ammonia (r(s) = 0.55, P < or = 0.001), and venous partial pressure of ammonia (r(s) = 0.52, P < or = 0.001).
CONCLUSION: Ammonia levels correlate with the severity of hepatic encephalopathy. Venous sampling is adequate for ammonia measurement. There appears to be no additional advantage of measuring the partial pressure of ammonia compared with total ammonia levels.

PMID 12637132  Am J Med. 2003 Feb 15;114(3):188-93.
著者: Masayuki Ikeda, Takashi Matsunaga, Noritsugu Irabu, Shohji Yoshida
雑誌名: BMJ. 2002 Oct 12;325(7368):800.
Abstract/Text OBJECTIVES: To determine whether any vital signs can be used to quickly identify brain lesions in patients with impaired consciousness.
DESIGN: Cross sectional observational study.
SETTING: Emergency department of an urban hospital, Japan.
PARTICIPANTS: 529 consecutive patients (mean age 65 years) presenting with impaired consciousness (score <15 on the Glasgow coma scale) during 2000.
MAIN OUTCOME MEASURES: The receiver operating characteristic curve was used to quantify the relation between the vital signs on arrival and the final diagnosis of a brain lesion. Stratum specific likelihood ratios were calculated to define strata with optimal discriminating power.
RESULTS: 312 (59%) had a brain lesion which accounted for the impaired consciousness. The area under the receiver operating curve for systolic blood pressure was 0.90 (SE 0.01), indicating significantly higher accuracy (P<0.01) in the identification of a brain lesion than using diastolic pressure 0.82 (0.02) or pulse rate 0.63 (0.03). Likelihood ratios for systolic blood pressure lower than 90 mm Hg were less than 0.04, and those for systolic pressure higher than 170 mm Hg were greater than 6.09.
CONCLUSIONS: Systolic blood pressure is useful for diagnosing brain lesions in patients with impaired consciousness.

PMID 12376438  BMJ. 2002 Oct 12;325(7368):800.
著者: M Touger, E J Gallagher, J Tyrell
雑誌名: Ann Emerg Med. 1995 Apr;25(4):481-3.
Abstract/Text STUDY OBJECTIVE: To test the hypothesis that venous carboxyhemoglobin (V-COHb) levels accurately predict arterial (A-COHb) levels.
DESIGN: Prospective comparison of A-COHb and V-COHb levels in patients with suspected carbon monoxide (CO) poisoning.
SETTING: Municipal hospital emergency department with contiguous multiplace hyperbaric chamber staffed 24 hours a day.
PARTICIPANTS: Unselected convenience sample of 61 adults with suspected CO toxicity.
INTERVENTION: Simultaneous sampling of arterial and venous blood.
RESULTS: Correlation between V-COHb and A-COHb showed an r value of .99 (95%CI, .99 to .99), and an r2 value of .98. Agreement between V-COHb and A-COHb levels was examined by use of a plot of arteriovenous differences against the mean of the two measurements. The mean arteriovenous difference was .15% COHb (95%CI, .13% to .45%), with 95% of the differences ranging from 2.4% COHb to -2.1% COHb.
CONCLUSION: Venous COHb levels predict arterial levels with a high degree of accuracy. Patients with suspected CO poisoning can be screened with the use of venous blood, without the need for arterial puncture.

PMID 7710152  Ann Emerg Med. 1995 Apr;25(4):481-3.
著者: Allan R Tunkel, Barry J Hartman, Sheldon L Kaplan, Bruce A Kaufman, Karen L Roos, W Michael Scheld, Richard J Whitley
雑誌名: Clin Infect Dis. 2004 Nov 1;39(9):1267-84. doi: 10.1086/425368. Epub 2004 Oct 6.
Abstract/Text
PMID 15494903  Clin Infect Dis. 2004 Nov 1;39(9):1267-84. doi: 10.1086・・・
著者: Ari R Joffe
雑誌名: J Intensive Care Med. 2007 Jul-Aug;22(4):194-207. doi: 10.1177/0885066607299516.
Abstract/Text There has been controversy regarding the risk of cerebral herniation caused by a lumbar puncture (LP) in acute bacterial meningitis (ABM). This review discusses in detail the issues involved in this controversy. Cerebral herniation occurs in about 5% of patients with ABM, accounting for about 30% of the mortality. In many reports, LP is temporally strongly associated with this event of herniation and is most likely causative based on pathophysiologic arguments. Although a computed tomography (CT) scan of the head is useful to find contraindications to an LP, a normal CT scan in ABM does not mean that an LP is safe. Clinical signs of "impending" herniation are the best predictors of when to delay an LP because of the risk of precipitating herniation, even with a normal CT scan. Some of these clinical signs to be considered are deteriorating level of consciousness (particularly to a Glasgow Coma Scale of
PMID 17712055  J Intensive Care Med. 2007 Jul-Aug;22(4):194-207. doi: ・・・
著者: Stephen J Wolf, Eric J Lavonas, Edward P Sloan, Andy S Jagoda, American College of Emergency Physicians
雑誌名: Ann Emerg Med. 2008 Feb;51(2):138-52. doi: 10.1016/j.annemergmed.2007.10.012.
Abstract/Text This clinical policy focuses on critical issues concerning the management of adult patients presenting to the emergency department (ED) with acute symptomatic carbon monoxide (CO) poisoning. The subcommittee reviewed the medical literature relevant to the questions posed. The critical questions are: Should hyperbaric oxygen (HBO2) therapy be used for the treatment of patients with acute CO poisoning; and Can clinical or laboratory criteria identify CO-poisoned patients who are most or least likely to benefit from this therapy. Recommendations are provided on the basis of the strength of evidence of the literature. Level A recommendations represent patient management principles that reflect a high degree of clinical certainty; Level B recommendations represent patient management principles that reflect moderate clinical certainty; and Level C recommendations represent other patient management strategies that are based on preliminary, inconclusive, or conflicting evidence, or based on committee consensus. This clinical policy is intended for physicians working in hospital-based EDs.

PMID 18206551  Ann Emerg Med. 2008 Feb;51(2):138-52. doi: 10.1016/j.an・・・
著者: Nick A Buckley, David N Juurlink, Geoff Isbister, Michael H Bennett, Eric J Lavonas
雑誌名: Cochrane Database Syst Rev. 2011 Apr 13;(4):CD002041. doi: 10.1002/14651858.CD002041.pub3. Epub 2011 Apr 13.
Abstract/Text BACKGROUND: Poisoning with carbon monoxide (CO) remains an important cause of accidental and intentional injury worldwide. Several unblinded non-randomized trials have suggested that the use of hyperbaric oxygen (HBO) prevents the development of neurological sequelae. This has led to the widespread use of HBO in the management of patients with carbon monoxide poisoning.
OBJECTIVES: To examine randomised trials of the efficacy of hyperbaric oxygen (HBO) compared to normobaric oxygen (NBO) for the prevention of neurologic sequelae in patients with acute carbon monoxide poisoning.
SEARCH STRATEGY: We searched the following electronic databases; Cochrane Injuries Group Specialised Register (searched June 2010), Cochrane Central Register of Controlled Trials (The Cochrane Library 2010, Issue 2), MEDLINE (Ovid SP) 1950 to June 2010, EMBASE (Ovid SP) 1980 to June 2010, ISI Web of Science: Science Citation Index Expanded (SCI-EXPANDED) 1970 to June 2010, ISI Web of Science: Conference Proceedings Citation Index-Science (CPCI-S) 1990 to June 2010.
SELECTION CRITERIA: All randomised controlled trials of HBO compared to NBO, involving non-pregnant adults who are acutely poisoned with carbon monoxide (regardless of severity).
DATA COLLECTION AND ANALYSIS: Two authors independently extracted from each trial information on: the number of randomised patients, types of participants, the dose and duration of the intervention, and the prevalence of neurologic symptoms at follow-up.
MAIN RESULTS: Seven randomised controlled trials of varying quality were identified; one was excluded because it did not evaluate clinical outcomes. Of the six remaining trials involving 1361 participants, two found a beneficial effect of HBO for the reduction of neurologic sequelae at one month, while four others did not. One of these is an incomplete publication (an abstract of an interim analysis). Although pooled random effects meta-analysis does not suggest a significant benefit from HBOT (OR for neurological deficits 0.78, 95%CI 0.54 to 1.12), significant methodologic and statistical heterogeneity was apparent among the trials, and this result should be interpreted cautiously. Moreover, design or analysis flaws were evident in all trials. Importantly, the conclusions of one positive trial may have been influenced by failure to adjust for multiple hypothesis testing, while interpretation of the other positive trial is hampered by a high risk of bias introduced during the analysis including an apparent change in the primary outcome. Both were also stopped early 'for benefit', which is likely to have inflated the observed effect. In contrast three negative trials had low power to detect a benefit of HBO due to exclusion of severely poisoned patients in two and very poor follow-up in the other. One trial that was said to be finished around eight years ago has not reported the final analysis in any forum.
AUTHORS' CONCLUSIONS: Existing randomised trials do not establish whether the administration of HBO to patients with carbon monoxide poisoning reduces the incidence of adverse neurologic outcomes. Additional research is needed to better define the role, if any, of HBO in the treatment of patients with carbon monoxide poisoning. This research question is ideally suited to a multi-center randomised controlled trial.

PMID 21491385  Cochrane Database Syst Rev. 2011 Apr 13;(4):CD002041. d・・・
著者: Lewis B Morgenstern, J Claude Hemphill, Craig Anderson, Kyra Becker, Joseph P Broderick, E Sander Connolly, Steven M Greenberg, James N Huang, R Loch MacDonald, Steven R Messé, Pamela H Mitchell, Magdy Selim, Rafael J Tamargo, American Heart Association Stroke Council and Council on Cardiovascular Nursing
雑誌名: Stroke. 2010 Sep;41(9):2108-29. doi: 10.1161/STR.0b013e3181ec611b. Epub 2010 Jul 22.
Abstract/Text PURPOSE: The aim of this guideline is to present current and comprehensive recommendations for the diagnosis and treatment of acute spontaneous intracerebral hemorrhage.
METHODS: A formal literature search of MEDLINE was performed. Data were synthesized with the use of evidence tables. Writing committee members met by teleconference to discuss data-derived recommendations. The American Heart Association Stroke Council's Levels of Evidence grading algorithm was used to grade each recommendation. Prerelease review of the draft guideline was performed by 6 expert peer reviewers and by the members of the Stroke Council Scientific Statements Oversight Committee and Stroke Council Leadership Committee. It is intended that this guideline be fully updated in 3 years' time.
RESULTS: Evidence-based guidelines are presented for the care of patients presenting with intracerebral hemorrhage. The focus was subdivided into diagnosis, hemostasis, blood pressure management, inpatient and nursing management, preventing medical comorbidities, surgical treatment, outcome prediction, rehabilitation, prevention of recurrence, and future considerations.
CONCLUSIONS: Intracerebral hemorrhage is a serious medical condition for which outcome can be impacted by early, aggressive care. The guidelines offer a framework for goal-directed treatment of the patient with intracerebral hemorrhage.

PMID 20651276  Stroke. 2010 Sep;41(9):2108-29. doi: 10.1161/STR.0b013e・・・
著者: Craig S Anderson, Yining Huang, Ji Guang Wang, Hisatomi Arima, Bruce Neal, Bin Peng, Emma Heeley, Christian Skulina, Mark W Parsons, Jong Sung Kim, Qing Ling Tao, Yue Chun Li, Jian Dong Jiang, Li Wen Tai, Jin Li Zhang, En Xu, Yan Cheng, Stephane Heritier, Lewis B Morgenstern, John Chalmers, INTERACT Investigators
雑誌名: Lancet Neurol. 2008 May;7(5):391-9. doi: 10.1016/S1474-4422(08)70069-3. Epub 2008 Apr 7.
Abstract/Text BACKGROUND: There is much uncertainty about the effects of early lowering of elevated blood pressure (BP) after acute intracerebral haemorrhage (ICH). Our aim was to assess the safety and efficiency of this treatment, as a run-in phase to a larger trial.
METHODS: Patients who had acute spontaneous ICH diagnosed by CT within 6 h of onset, elevated systolic BP (150-220 mm Hg), and no definite indication or contraindication to treatment were randomly assigned to early intensive lowering of BP (target systolic BP 140 mm Hg; n=203) or standard guideline-based management of BP (target systolic BP 180 mm Hg; n=201). The primary efficacy endpoint was proportional change in haematoma volume at 24 h; secondary efficacy outcomes included other measurements of haematoma volume. Safety and clinical outcomes were assessed for up to 90 days. Analysis was by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT00226096.
FINDINGS: Baseline characteristics of patients were similar between groups, but mean haematoma volumes were smaller in the guideline group (12.7 mL, SD 11.6) than in the intensive group (14.2 mL, SD 14.5). From randomisation to 1 h, mean systolic BP was 153 mm Hg in the intensive group and 167 mm Hg in the guideline group (difference 13.3 mm Hg, 95% CI 8.9-17.6 mm Hg; p<0.0001); from 1 h to 24 h, BP was 146 mm Hg in the intensive group and 157 mm Hg in the guideline group (10.8 mm Hg, 95% CI 7.7-13.9 mm Hg; p<0.0001). Mean proportional haematoma growth was 36.3% in the guideline group and 13.7% in the intensive group (difference 22.6%, 95% CI 0.6-44.5%; p=0.04) at 24 h. After adjustment for initial haematoma volume and time from onset to CT, median haematoma growth differed between the groups with p=0.06; the absolute difference in volume between groups was 1.7 mL (95% CI -0.5 to 3.9, p=0.13). Relative risk of haematoma growth >or=33% or >or=12.5 mL was 36% lower (95% CI 0-59%, p=0.05) in the intensive group than in the guideline group. The absolute risk reduction was 8% (95% CI -1.0 to 17%, p=0.05). Intensive BP-lowering treatment did not alter the risks of adverse events or secondary clinical outcomes at 90 days.
INTERPRETATION: Early intensive BP-lowering treatment is clinically feasible, well tolerated, and seems to reduce haematoma growth in ICH. A large randomised trial is needed to define the effects on clinical outcomes across a broad range of patients with ICH.
FUNDING: National Health and Medical Research Council of Australia.

PMID 18396107  Lancet Neurol. 2008 May;7(5):391-9. doi: 10.1016/S1474-・・・
著者: Antihypertensive Treatment of Acute Cerebral Hemorrhage (ATACH) investigators
雑誌名: Crit Care Med. 2010 Feb;38(2):637-48. doi: 10.1097/CCM.0b013e3181b9e1a5.
Abstract/Text OBJECTIVE: To determine the feasibility and acute (i.e., within 72 hrs) safety of three levels of systolic blood pressure reduction in subjects with supratentorial intracerebral hemorrhage treated within 6 hrs after symptom onset.
DESIGN: A traditional phase I, dose-escalation, multicenter prospective study.
SETTINGS: Emergency departments and intensive care units.
PATIENTS: Patients with intracerebral hemorrhage with elevated systolic blood pressure > or = 170 mm Hg who present to the emergency department within 6 hrs of symptom onset.
INTERVENTION: Intravenous nicardipine to reduce systolic blood pressure to a target of: (1) 170 to 200 mm Hg in the first cohort of patients; (2) 140 to 170 mm Hg in the second cohort; and (3) 110 to 140 mm Hg in the third cohort.
MEASUREMENTS AND MAIN RESULTS: Primary outcomes of interest were: (1) treatment feasibility (achieving and maintaining the systolic blood pressure goals for 18-24 hrs); (2) neurologic deterioration within 24 hrs; and (3) serious adverse events within 72 hrs. Safety stopping rules based on neurologic deterioration and serious adverse events were prespecified and approved by an NIH-appointed Data and Safety Monitoring Board, which provided oversight on subject safety. Each subject was followed-up for 3 months to preliminarily assess mortality and the clinical outcomes. A total of 18, 20, and 22 patients were enrolled in the respective three tiers of systolic blood pressure treatment goals. Overall, 9 of 60 patients had treatment failures (all in the last tier). A total of seven subjects with neurologic deterioration were observed: one (6%), two (10%), and four (18%) in tier one, two, and three, respectively. Serious adverse events were observed in one subject (5%) in tier two and in three subjects (14%) in tier three. However, the safety stopping rule was not activated in any of the tiers. Three (17%), two (10%), and five (23%) subjects in tiers one, two, and three, respectively, died within 3 months.
CONCLUSIONS: The observed proportions of neurologic deterioration and serious adverse events were below the prespecified safety thresholds, and the 3-month mortality rate was lower than expected in all systolic blood pressure tiers. The results form the basis of a larger randomized trial addressing the efficacy of systolic blood pressure reduction in patients with intracerebral hemorrhage.

PMID 19770736  Crit Care Med. 2010 Feb;38(2):637-48. doi: 10.1097/CCM.・・・
著者: M Privitera, M Hoffman, J L Moore, D Jester
雑誌名: Epilepsy Res. 1994 Jun;18(2):155-66.
Abstract/Text Subtypes of status epilepticus (SE) without tonic-clonic convulsions (nontonic-clonic SE) present as altered consciousness sometimes with subtle motor activity and are important to consider in the differential diagnosis of patients with unexplained altered consciousness. Other patients may have altered consciousness with intermittent ictal activity on electroencephalography (EEG) that represents probable SE, but have other medical conditions that may be contributing to altered consciousness. EEG is the only reliable way to make the diagnosis of nontonic-clonic SE and we make emergency EEG available on a 24-h basis at our hospital. To determine how often definite or probable nontonic-clonic SE was detected by EEG we prospectively collected data on all cases where physicians ordered EEG to evaluate altered consciousness or possible SE. Out of 198 cases with altered consciousness but no clinical convulsions, 74 (37%) showed EEG and clinical evidence of definite or probable nontonic-clonic SE. Forty-two episodes (57%) were probable or definite complex partial SE, 29 (39%) were probable or definite subtle generalized SE, and three (4%) were myoclonic SE. In 23 SE cases altered consciousness was the only clinical sign at the time of diagnosis; subtle motor activity was present in 36 others. Neither clinical signs nor prior history predicted which patients showed SE on EEG. Nontonic-clonic SE followed a cerebral infarction in 16 cases. Contrary to other reports, we found no relationship between duration of SE and EEG pattern. Subtle generalized SE occurred most commonly in the setting of a diffuse brain injury rather than evolving from convulsive SE. This study demonstrates that nontonic-clonic SE is a common finding in patients with unexplained altered consciousness and EEG is necessary in the evaluation of these patients.

PMID 7957038  Epilepsy Res. 1994 Jun;18(2):155-66.
著者: J Claassen, S A Mayer, R G Kowalski, R G Emerson, L J Hirsch
雑誌名: Neurology. 2004 May 25;62(10):1743-8.
Abstract/Text OBJECTIVE: To identify patients most likely to have seizures documented on continuous EEG (cEEG) monitoring and patients who require more prolonged cEEG to record the first seizure.
METHODS: Five hundred seventy consecutive patients who underwent cEEG monitoring over a 6.5-year period were reviewed for the detection of subclinical seizures or evaluation of unexplained decrease in level of consciousness. Baseline demographic, clinical, and EEG findings were recorded and a multivariate logistic regression analysis performed to identify factors associated with 1) any EEG seizure activity and 2) first seizure detected after >24 hours of monitoring.
RESULTS: Seizures were detected in 19% (n = 110) of patients who underwent cEEG monitoring; the seizures were exclusively nonconvulsive in 92% (n = 101) of these patients. Among patients with seizures, 89% (n = 98) were in intensive care units at the time of monitoring. Electrographic seizures were associated with coma (odds ratio [OR] 7.7, 95% CI 4.2 to 14.2), age <18 years (OR 6.7, 95% CI 2.8 to 16.2), a history of epilepsy (OR 2.7, 95% CI 1.3 to 5.5), and convulsive seizures during the current illness prior to monitoring (OR 2.4, 95% CI 1.4 to 4.3). Seizures were detected within the first 24 hours of cEEG monitoring in 88% of all patients who would eventually have seizures detected by cEEG. In another 5% (n = 6), the first seizure was recorded on monitoring day 2, and in 7% (n = 8), the first seizure was detected after 48 hours of monitoring. Comatose patients were more likely to have their first seizure recorded after >24 hours of monitoring (20% vs 5% of noncomatose patients; OR 4.5, p = 0.018).
CONCLUSIONS: CEEG monitoring detected seizure activity in 19% of patients, and the seizures were almost always nonconvulsive. Coma, age <18 years, a history of epilepsy, and convulsive seizures prior to monitoring were risk factors for electrographic seizures. Comatose patients frequently required >24 hours of monitoring to detect the first electrographic seizure.

PMID 15159471  Neurology. 2004 May 25;62(10):1743-8.
著者: Josep Dalmau, Thais Armangué, Jesús Planagumà, Marija Radosevic, Francesco Mannara, Frank Leypoldt, Christian Geis, Eric Lancaster, Maarten J Titulaer, Myrna R Rosenfeld, Francesc Graus
雑誌名: Lancet Neurol. 2019 Jul 17;. doi: 10.1016/S1474-4422(19)30244-3. Epub 2019 Jul 17.
Abstract/Text The identification of anti-NMDA receptor (NMDAR) encephalitis about 12 years ago made it possible to recognise that some patients with rapidly progressive psychiatric symptoms or cognitive impairment, seizures, abnormal movements, or coma of unknown cause, had an autoimmune disease. In this disease, autoantibodies serve as a diagnostic marker and alter NMDAR-related synaptic transmission. At symptom onset, distinguishing the disease from a primary psychiatric disorder is challenging. The severity of symptoms often requires intensive care. Other than clinical assessment, no specific prognostic biomarkers exist. The disease is more prevalent in women (with a female to male ratio of around 8:2) and about 37% of patients are younger than 18 years at presentation of the disease. Tumours, usually ovarian teratoma, and herpes simplex encephalitis are known triggers of NMDAR autoimmunity. About 80% of patients improve with immunotherapy and, if needed, tumour removal, but the recovery is slow. Animal models have started to reveal the complexity of the underlying pathogenic mechanisms and will lead to novel treatments beyond immunotherapy. Future studies should aim at identifying prognostic biomarkers and treatments that accelerate recovery.

Copyright © 2019 Elsevier Ltd. All rights reserved.
PMID 31326280  Lancet Neurol. 2019 Jul 17;. doi: 10.1016/S1474-4422(19・・・
著者: Shamik Bhattacharyya, R Ryan Darby, Pooja Raibagkar, L Nicolas Gonzalez Castro, Aaron L Berkowitz
雑誌名: Neurology. 2016 Mar 8;86(10):963-71. doi: 10.1212/WNL.0000000000002455. Epub 2016 Feb 17.
Abstract/Text Delirium is a common and costly complication of hospitalization. Although medications are a known cause of delirium, antibiotics are an underrecognized class of medications associated with delirium. In this article, we comprehensively review the clinical, radiologic, and electrophysiologic features of antibiotic-associated encephalopathy (AAE). AAE can be divided into 3 unique clinical phenotypes: encephalopathy commonly accompanied by seizures or myoclonus arising within days after antibiotic administration (caused by cephalosporins and penicillin); encephalopathy characterized by psychosis arising within days of antibiotic administration (caused by quinolones, macrolides, and procaine penicillin); and encephalopathy accompanied by cerebellar signs and MRI abnormalities emerging weeks after initiation of antibiotics (caused by metronidazole). We correlate these 3 clinical phenotypes with underlying pathophysiologic mechanisms of antibiotic neurotoxicity. Familiarity with these types of antibiotic toxicity can improve timely diagnosis of AAE and prompt antibiotic discontinuation, reducing the time patients spend in the delirious state.

© 2016 American Academy of Neurology.
PMID 26888997  Neurology. 2016 Mar 8;86(10):963-71. doi: 10.1212/WNL.0・・・
著者: Patrick Latour, Arnaud Biraben, Elisabeth Polard, Danièle Bentué-Ferrer, Anne Beauplet, Olivier Tribut, Hervé Allain
雑誌名: Hum Psychopharmacol. 2004 Apr;19(3):193-203. doi: 10.1002/hup.575.
Abstract/Text Six severe epileptic patients developed stuporous encephalopathy with marked cognitive impairment when topiramate (TPM) and sodium valproate (VPA) were coprescribed for five patients, and when monotherapy with TPM was introduced for one patient. In four patients, ammonaemia increased and then returned to normal after TPM or VPA withdrawal. This severe potential side effect must be recognized. Moreover two distinct mechanisms might explain this toxicity: (1). a pharmacokinetic interaction between VPA and TPM, leading to hyperammonaemia, (2). a pharmacodynamic mechanism due to a direct toxicity of TPM in at-risk epileptic patients.

Copyright 2004 John Wiley & Sons, Ltd.
PMID 15079854  Hum Psychopharmacol. 2004 Apr;19(3):193-203. doi: 10.10・・・
著者: P J Shaw, T J Walls, P K Newman, P G Cleland, N E Cartlidge
雑誌名: Neurology. 1991 Feb;41(2 ( Pt 1)):228-33. doi: 10.1212/wnl.41.2_part_1.228.
Abstract/Text We describe 5 patients with a relapsing encephalopathy in association with Hashimoto's disease and high titers of anti-thyroid antibodies. The presentation is usually with a subacute onset of confusion, alteration in conscious level, and focal or generalized seizures. The relapsing course, association with myoclonus or tremulousness, and episodes of stroke-like deterioration are characteristic features. The long-term prognosis is favorable with steroid therapy, though additional immunosuppressive therapy may be required. Neurologic investigation typically shows a diffusely abnormal EEG, high CSF protein level without pleocytosis, and normal brain CT and cerebral angiogram. Isotope brain scan may show patchy abnormal uptake. Hashimoto's encephalopathy should be recognized as a definite neurologic entity and added to the list of CNS complications of thyroid disease.

PMID 1992366  Neurology. 1991 Feb;41(2 ( Pt 1)):228-33. doi: 10.1212/・・・
著者: Makoto Yoneda
雑誌名: Brain Nerve. 2018 Apr;70(4):305-314. doi: 10.11477/mf.1416201004.
Abstract/Text Encephalopathy occasionally occurs in association with thyroid disorders, most of which are treatable. These encephalopathies include a neuropsychiatric disorder associated with hypothyroidism named myxedema encephalopathy. Moreover, Hashimoto's encephalopathy (HE) has been recognized as a new clinical disease based on an autoimmune mechanism associated with Hashimoto's thyroiditis, and can be successfully treated using steroids. Recently, we discovered that the serum autoantibodies against the NH2-terminal of α-enolase (NAE) were a highly specific diagnostic biomarker for HE. We analyzed the serum anti-NAE autoantibodies and the clinical features in many cases of HE from institutions across Japan and other countries. About half the patients with HE had anti-NAE antibodies. Patient age was widely distributed with two peaks (around 20-30 years old and 60-80 years old). Most patients with HE were in euthyroid states and all patients had anti-thyroid antibodies. The common neuropsychiatric features include disturbance of consciousness, psychosis, cognitive dysfunction, involuntary movements, seizures, and ataxia. Electroencephalograph (EEG) abnormalities and decreased cerebral blood flow on brain single positron emission computed tomography are common findings, whereas abnormalities on brain magnetic resonance imaging are rare. Patients with HE present with various clinical phenotypes such as an acute encephalopathy form and chronic psychiatric form. Other clinical forms include limbic encephalitis, progressive cerebellar ataxia, and Creutzfeldt-Jakob disease (CJD)-mimic forms. The cerebellar ataxia form of HE clinically mimics spinocerebellar degeneration (SCD) and is characterized by the absence of nystagmus, absent or mild cerebellar atrophy, and lazy background activity on EEG. Taken together, clinicians should pay attention to the possibility of encephalopathy associated with thyroid disorders.

PMID 29632279  Brain Nerve. 2018 Apr;70(4):305-314. doi: 10.11477/mf.1・・・
著者: J Domínguez-Carral, V Puertas-Martín, I Carreras-Sáez, A I Maraña-Pérez, T Escobar-Delgado, J J García-Peñas
雑誌名: An Pediatr (Barc). 2014 May;80(5):293-8. doi: 10.1016/j.anpedi.2013.06.034. Epub 2013 Oct 6.
Abstract/Text INTRODUCTION: Intussusception is a potentially severe obstructive disease that occurs when a more proximal portion of bowel invaginates into a more distal part of the bowel. Patients with intussusception often present with a wide range of non-specific systemic symptoms, with less than one quarter presenting with the classic triad of vomiting, abdominal pain, and bloody stools. An acute change in level of consciousness could be the only clinical symptom of this disorder.
OBJECTIVES: To ascertain the frequency and nature of the neurological symptoms in children with intussusception, and to describe the characteristics of the patients presenting in this atypical way.
PATIENTS AND METHODS: We retrospectively reviewed the records of 351 children presenting with intussusception from 2000 to 2012. General epidemiological data, abdominal and neurological signs and symptoms, duration of symptoms and effectiveness of treatment, were analysed in all patients.
RESULTS: Of the 351 patients studied, 15 (4.27%) had one or more neurological symptoms recorded at presentation, with lethargy being the most frequent (66.66%), followed by hypotonia, generalized weakness, paroxysmal events, and fluctuating consciousness. Sixty per cent of these fifteen patients showed isolated neurological symptomatology, and eleven of them (73.3%) needed a laparotomy to reduce the intussusception.
CONCLUSIONS: Intussusception should be considered in the differential diagnosis in infants and young children presenting as a pediatric emergency with lethargy, hypotonia, generalized weakness, paroxysmal events and/or sudden changes in consciousness, even in the absence of the classical symptoms of intussusception. An early recognition of intussusception may improve the global prognosis and avoid ischaemic intestinal sequelae.

Copyright © 2013 Asociación Española de Pediatría. Published by Elsevier Espana. All rights reserved.
PMID 24103235  An Pediatr (Barc). 2014 May;80(5):293-8. doi: 10.1016/j・・・
著者: A Foy, S March, V Drinkwater
雑誌名: Alcohol Clin Exp Res. 1988 Jun;12(3):360-4.
Abstract/Text A modified version of the Clinical Institute Withdrawal Assessment Scale (CIWA) was used in the management of alcohol withdrawal in a general hospital. Patients who developed seizures or confusion were noted to score higher on the scale, even before these complications, than patients who remained uncomplicated (21.7 +/- 1.2 compared to 15.6 +/- 0.55). When the score was used as a guide for treatment, it was found that patients scoring greater than 15 were at significantly increased risk of severe alcohol withdrawal if they remained untreated (RR, 3.72; 95% confidence interval, 2.85-4.85). The higher the score the greater this relative risk. Some patients however, still suffered complicated withdrawals although their scores were low or they were apparently adequately treated. It is concluded that the use of an objective clinical scale of alcohol withdrawal is valuable in a general hospital to identify those patients in early withdrawal who need sedation to avoid complication. There will however, be a small group of patients whose clinical course will be difficult to predict and further work is needed to determine the reasons for this.

PMID 3044163  Alcohol Clin Exp Res. 1988 Jun;12(3):360-4.
著者: Alan H Hall, Richard Dart, Gregory Bogdan
雑誌名: Ann Emerg Med. 2007 Jun;49(6):806-13. doi: 10.1016/j.annemergmed.2006.09.021. Epub 2006 Nov 13.
Abstract/Text Cyanide poisoning must be seriously considered in victims of smoke inhalation from enclosed space fires; it is also a credible terrorism threat agent. The treatment of cyanide poisoning is empiric because laboratory confirmation can take hours or days. Empiric treatment requires a safe and effective antidote that can be rapidly administered by either out-of-hospital or emergency department personnel. Among several cyanide antidotes available, sodium thiosulfate and hydroxocobalamin have been proposed for use in these circumstances. The evidence available to assess either sodium thiosulfate or hydroxocobalamin is incomplete. According to recent safety and efficacy studies in animals and human safety and uncontrolled efficacy studies, hydroxocobalamin seems to be an appropriate antidote for empiric treatment of smoke inhalation and other suspected cyanide poisoning victims in the out-of-hospital setting. Sodium thiosulfate can also be administered in the out-of-hospital setting. The efficacy of sodium thiosulfate is based on individual case studies, and there are contradictory conclusions about efficacy in animal models. The onset of antidotal action of sodium thiosulfate may be too slow for it to be the only cyanide antidote for emergency use. Hydroxocobalamin is being developed for potential introduction in the United States and may represent a new option for emergency personnel in cases of suspected or confirmed cyanide poisoning in the out-of-hospital setting.

PMID 17098327  Ann Emerg Med. 2007 Jun;49(6):806-13. doi: 10.1016/j.an・・・
著者: S R Benbadis, C A Sila, R L Cristea
雑誌名: J Gen Intern Med. 1994 Sep;9(9):485-7.
Abstract/Text OBJECTIVE: To determine the frequency with which an acute confusional state is caused by a stroke and to evaluate the usefulness of obtaining computed tomography scans in this setting.
DESIGN: Retrospective analysis.
SETTING: Tertiary referral center.
PATIENTS: The authors reviewed 127 neurology consultations requested for patients presenting with acute and apparently isolated mental status changes. The mean age was 62 years.
RESULTS: Nine (7%) of the 127 patients were thought to have suffered mental status changes as a result of an acute stroke: one subarachnoid hemorrhage, and eight ischemic strokes. There was no intracerebral hemorrhage. The locations of the infarcts were: right frontoparietal (four patients), bilateral occipital (two patients), bilateral frontal (two patients), and right pontine (one patient, for whom the causality of the stroke was uncertain). Of those nine stroke patients presenting with isolated mental symptoms, six (66%) had some focal abnormality on neurologic examination. Only three (2.7%) of the 109 patients with no focal findings were ultimately diagnosed as having strokes, and one of these had a subarachnoid hemorrhage.
CONCLUSIONS: Stroke was a relatively rare cause of acute confusional syndrome. The neurologic examination had a very high negative predictive value (97%) and was reliable in selecting patients who should undergo an imaging study.

PMID 7996290  J Gen Intern Med. 1994 Sep;9(9):485-7.
著者: B J Naughton, M Moran, Y Ghaly, C Michalakes
雑誌名: Acad Emerg Med. 1997 Dec;4(12):1107-10.
Abstract/Text OBJECTIVE: 1) To examine the ordering of head CT scans in elder patients with delirium and cognitive impairment; and 2) to report CT scan findings associated with these conditions.
METHODS: This was a 2-part study. Part 1 was a prospective, observational study of 560 adults > 70 years of age evaluated at 3 separate EDs using a 200-hour stratified sampling process at each ED. During Part 1, the frequencies of specific findings (i.e., delirium, impaired consciousness, and impaired cognition) and CT scan rates for these groups were determined. Part 2 was a retrospective analysis of CT scan reports and medical records (n = 279) for patients > 70 years of age in the prospective sample (n = 79) and from a sample (n = 200) of CT scans obtained at a fourth ED. Part 2 examined clinical findings detected in the ED to determine those factors that were associated with acute findings on CT scan.
RESULTS: Part 1: There were 333 (59.4%) patients prospectively classified as having impaired cognition, impaired consciousness, or delirium; 79 (23.7%) of these patients had a head CT scan. Of these 3 groups, delirious patients were more frequently scanned (p < 0.001). Part 2: Of 279 CT scans, 42 (15.0%) were positive for an acute condition (hemorrhage, hematoma, space-occupying lesion, infarct). Of 42 positive scans, 40 (95.1%) were found in the 102 (36.6%) patients with either impaired consciousness or a new focal neurologic finding detected in the ED.
CONCLUSIONS: Considerable variability in ED CT scan ordering exists for elder patients with neurologic findings. Impaired consciousness and/or new focal neurologic signs are associated with acute findings on CT scan in elder patients. Acute CT abnormalities are uncommon in elder ED patients with other neurologic findings. Additional prospective evaluation is warranted prior to guideline development for CT scans in this patient population.

PMID 9408423  Acad Emerg Med. 1997 Dec;4(12):1107-10.
著者: Matthijs C Brouwer, Peter McIntyre, Jan de Gans, Kameshwar Prasad, Diederik van de Beek
雑誌名: Cochrane Database Syst Rev. 2010 Sep 8;(9):CD004405. doi: 10.1002/14651858.CD004405.pub3. Epub 2010 Sep 8.
Abstract/Text BACKGROUND: In experimental studies, the outcome of bacterial meningitis has been related to the severity of inflammation in the subarachnoid space. Corticosteroids reduce this inflammatory response.
OBJECTIVES: To examine the effect of adjuvant corticosteroid therapy versus placebo on mortality, hearing loss and neurological sequelae in people of all ages with acute bacterial meningitis.
SEARCH STRATEGY: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2010, issue 1), MEDLINE (1966 to February 2010), EMBASE (1974 to February 2010) and Current Contents (2001 to February 2010).
SELECTION CRITERIA: Randomised controlled trials (RCTs) of corticosteroids for acute bacterial meningitis.
DATA COLLECTION AND ANALYSIS: We scored RCTs for methodological quality. We collected outcomes and adverse effects. We performed subgroup analyses for children and adults, causative organisms, low-income versus high-income countries, time of steroid administration and study quality.
MAIN RESULTS: Twenty-four studies involving 4041 participants were included. Similar numbers of participants died in the corticosteroid and placebo groups (18.0% versus 20.0%; risk ratio (RR) 0.92, 95% confidence interval (CI) 0.82 to 1.04, P = 0.18). There was a trend towards lower mortality in adults receiving corticosteroids (RR 0.74, 95% CI 0.53 to 1.05, P = 0.09). Corticosteroids were associated with lower rates of severe hearing loss (RR 0.67, 95% CI 0.51 to 0.88), any hearing loss (RR 0.76, 95% CI 0.64 to 0.89) and neurological sequelae (RR 0.83, 95% CI 0.69 to 1.00).Subgroup analyses for causative organisms showed that corticosteroids reduced severe hearing loss in Haemophilus influenzae meningitis (RR 0.34, 95% CI 0.20 to 0.59) and reduced mortality in Streptococcus pneumoniae meningitis (RR 0.84, 95% CI 0.72 to 0.98).In high-income countries, corticosteroids reduced severe hearing loss (RR 0.51, 95% CI 0.35 to 0.73), any hearing loss (RR 0.58, 95% CI 0.45 to 0.73) and short-term neurological sequelae (RR 0.64, 95% CI 0.48 to 0.85). There was no beneficial effect of corticosteroid therapy in low-income countries.Subgroup analysis for study quality showed no effect of corticosteroids on severe hearing loss in high quality studies.Corticosteroid treatment was associated with an increase in recurrent fever (RR 1.27, 95% CI 1.09 to 1.47), but not with other adverse events.
AUTHORS' CONCLUSIONS: Corticosteroids significantly reduced hearing loss and neurological sequelae, but did not reduce overall mortality. Data support the use of corticosteroids in patients with bacterial meningitis in high-income countries. We found no beneficial effect in low-income countries.

PMID 20824838  Cochrane Database Syst Rev. 2010 Sep 8;(9):CD004405. do・・・

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