抽象
本研究的目的是评估患者的肺结核(TB),急性呼吸衰竭(ARF)的死亡率的临床特点,预后和预测,并探讨在这种情况下,辅助使用糖皮质激素。
TB patients with ARF requiring mechanical ventilation (n = 90) were enrolled retrospectively during 1989–2006. The patients were divided into two groups: tuberculous pneumonia (TBP; n = 66), and miliary TB (MTB; n = 24).
该TBP患者比MTB老年患者(平均年龄68.0与五4。五 yrs), and the mean±sdTBP从入院到开始抗结核治疗的间隔时间长于MTB组(5.0±7.0)与2。8±2.5 days). However, there was no difference in in-hospital mortality rate between the two groups (68.2与58.3%)。在TBP患者中,多变量分析显示,高龄和冲击无关脓毒症患者与不良预后相关。即使使用皮质类固醇是在TBP患者的生存期预测,很难最终确定,因为回顾性研究设计的TBP与ARF糖皮质激素的疗效。
本研究揭示了随机对照试验的必要性,以明确糖皮质激素作为辅助治疗在治疗急性呼吸衰竭的结核性肺炎中的作用。
自20世纪50年代中期以来,结核病发病率有所下降,但自20世纪90年代中期以来,许多国家的结核病发病率开始上升。这种疾病的控制一直受到艾滋病毒同时感染的阻碍1和多重耐药性TB的出现2。活动性肺结核是急性呼吸衰竭的一种罕见的主要原因(ARF)3;然而,高死亡率最近报告ARF患者结核引起的4-6。
皮质类固醇是炎症的最重要的生理抑制剂。几个随机研究严重的患者的炎性病症,如儿茶酚胺依赖性脓毒性休克中显示功效,和皮质类固醇治疗的安全性7,8,严重的社区获得性肺炎9,10和早期急性呼吸窘迫综合征(ARDS)11,12。随着持续unresolving ARDS,在一些研究中观察到皮质类固醇治疗的有益作用13但这样的改进并没有在其他记录14。
糖皮质激素也已被用作治疗结核病的辅助手段。在这方面的有效使用皮质类固醇激素是充分证明了好肺外形式的疾病,如结核性脑膜炎15和结核性心包炎16。多项研究表明,在使用类固醇的同时,肺部浸润和腔体闭合的放射学分辨率更高;这些影响可能在重症患者中更为明显17,18。然而,使用皮质激素调节的严重炎症反应的有害影响尚未前瞻性的重症患者结核引起的急性肾功能衰竭的影响。
本研究的,因此,传导到:1)评估谁开发ARF需要机械通气韩国结核病患者的临床特征;2)确定的死亡率和住院死亡率的预测因子;和3)调查佐剂使用皮质类固醇的状态和这种治疗的对结果的影响。
材料和方法
耐心
The medical records of all relevant patients (aged >18 yrs) who had been admitted to the medical intensive care unit of the Asan Medical Center (Seoul, South Korea) between March 1989 and December 2006 were retrieved according to the following International Statistical Classification of Diseases and Related Health Problems, 10th revision, codes: A150–A153 and A160–A162 (TB of lung), and A190–A199 (miliary TB (MTB)). Medical records were reviewed and those patients selected who were bacteriologically or histologically diagnosed with active TB. Of these patients, 115 experienced ARF because of associated TB and were managed with invasive mechanical ventilation. Excluding 25 patients whose lungs had been extensively damaged by previous TB episodes, 90 patients were included in the final analysis of the present study. Of these 90 patients, 18 had already been diagnosed with TB at other hospitals and were then transferred to the Asan Medical Center, whereas the rest were diagnosed with TB after admission to the Asan Medical Center.
胸部摄影及资料收集
录取过程中获得的胸部X线检查由放射科医生的肺和肺医生重新分析。在意见分歧的情况下,肺科医师的观点占了上风。Based on radiographic findings, the patients were divided into the following two groups: tuberculous pneumonia (TBP; n = 66), and MTB (n = 24). TBP was defined as parenchymal consolidation with or without endobronchial spread mimicking bacterial pneumonia19。MTB被定义为双侧弥漫小米尺寸结节的存在。
记录年龄、性别、急性生理、年龄和慢性健康评估(APACHE) III评分、体重指数、结核病的危险因素、潜在疾病、既往抗结核治疗史、合并肺外结核和入院前症状持续时间,并进行组间比较。记录和比较痰耐酸杆菌涂片和培养数据以及药敏、动脉血气分析、血清白蛋白水平和住院死亡率等诊断结果。此外,在住院期间,还记录了弥散性血管内凝血(DIC)、伴随的ARDS、休克和器官衰竭。
本研究还研究了辅助使用皮质类固醇,包括剂量,从开始抗结核治疗的对激素治疗的持续时间和间隔的状态。重症结核病使用糖皮质激素在峨山医学中心并没有正式,在主治医生的自由裁量权被完全。
定义
DIC的存在或不存在是通过血小板计数,凝血酶原时间,部分凝血活酶时间,纤维蛋白原降解产物(FDP)水平来确定,d-dimer测定和纤维蛋白原水平。冲击被定义为用于血管加压药的必要条件。休克的病因分为感染性休克和冲击无关败血症,如心脏衰竭或脑血管意外。ARDS的诊断是基于欧美共识会议的共识标准20.。脓毒症被认为存在感染时,临床上怀疑与全身炎症反应的证据相结合的基础上,通过最近的国际共识会议所决定的标准21脓毒症休克定义为脓毒症合并低血压顽固性液体置换21。根据诺斯的标准器官功能衰竭被确诊等。22,多器官功能衰竭(multi - organ failure, MOF)被定义为多个器官功能衰竭。
统计分析
分类值,如性别比例和死亡率,用卡方Fisher的精确检验组之间进行比较。连续值,如年龄和APACHE III评分,使用非配对t检验和Wilcoxon秩和检验组间比较。所有的值都以平均值±sd或连续变量的范围的中位数,分类值的组数或百分比。在单变量分析的基础上,采用正逐步多元logistic回归模型评估影响ARF患者预后的独立危险因素,包括所有显著或几乎显著的参数(p<0.1)。p值<0.05被认为是显著的。
结果
患者特征
Baseline clinical and laboratory characteristics and risk factors for TB are listed in table 1⇓。44个HIV ELISAs均为阴性。所有患者的中位年龄为61.5岁(范围22-89岁),性别比例为1.5:1.0(男性:女性)。入院前症状持续时间为27±26天。糖尿病是最常见的潜在疾病,如表1所示⇓。胸片肺内空腔中存在25(27%)的患者。Diagnosis was confirmed by sputum AFB smear and/or culture (n = 80), bone marrow biopsy (n = 7) or transbronchial lung biopsy (n = 3). Drug susceptibility data were available for bacterial isolates from 24 patients; isolates from six cases showed single-drug resistance, bacteria from two patients exhibited multidrug resistance (MDR) and结核分枝杆菌其他16例患者表现出泛易感性。
医院课程和成果
平均住院时间(38±47)天,重症监护病房(21±27)天,机械通气(18±26)天。从入院到开始抗结核治疗的平均间隔时间为4.3±6.0天。44例(49%)患者使用了全身糖皮质激素。泼尼松龙当量的平均每日剂量为59±6.7 mg,皮质类固醇治疗的中位持续时间为20(范围7-120)天。在44名(81.8%)患者中,有36名患者将使用皮质类固醇用于治疗结核病引起的急性呼吸窘迫综合征。开始抗结核治疗和皮质类固醇治疗之间的中间间隔为2(0-12)天。在44名患者中,有8名患者在诊断为结核病之前立即开始使用全身糖皮质激素,以治疗另一种假定的疾病,如慢性阻塞性肺病(COPD;n = 6)或推定的隐源性组织肺炎(n = 2);然而,这些患者最终被诊断为结核病和相关的ARF。住院死亡率为65.6%(90 / 59)。 TB was the direct cause of death in 50 patients (including 34 cases of ARF and 16 cases of shock). Other causes of death were intestinal perforation (n = 1), arrhythmia (n = 4), pulmonary embolism (n = 2), massive aspiration (n = 1) and intracranial haemorrhage (n = 1).
结核性肺炎和粟粒性肺结核组间比较
Comparative data for the two groups are summarised in table 1⇑。The TBP patients were older than the MTB patients (median ages 68.0 and 54.5 yrs, respectively; p = 0.009). The mean interval from hospital admission to start of anti-TB treatment was longer in the TBP group than in the MTB group (5.0±7.0 and 2.8±2.5 days, respectively; p = 0.048); in addition, four patients for whom TB treatment was delayed for >14 days (15, 25, 28 and 30 days) were in the TBP group. Concomitant extrapulmonary TB, ARDS or DIC were more common in the MTB group than in the TBP group (all p<0.05). However, there were no significant differences in in-hospital mortality rates between the two groups (68.2 and 58.3%, respectively; p = 0.385).
要素按组预测住院死亡率
在TBP组中,单因素分析显示高龄、入院前症状持续时间较长、休克的存在与脓毒症无关、未使用类固醇是影响患者生存的因素(表2)⇓)。There were no significant differences in septic shock frequency, MOF, ARDS, number of lobes involved (based on chest radiography, which indicated the extent of disease; p = 0.448; data not shown) or presence of cavitation (70 and 67%, respectively; p = 0.860) between the survivor and nonsurvivor groups. Multivariate analysis revealed that advanced age and presence of shock unrelated to sepsis were independently associated with poor outcomes; however, the use of corticosteroids was a favourable prognostic factor for patients with TBP (table 3⇓)。
In the MTB group, unlike the TBP group, there were no factors predictive of nonsurvival (table 2⇑)。
结核性肺炎类固醇使用和不使用群体之间的比较
Among TBP patients, those receiving corticosteroid therapy showed a lower mortality rate (56.7%; 17 out of 30) than those not receiving corticosteroid therapy (77.8%; 28 out of 36; p = 0.046; table 4⇓)。在临床特征方面,如年龄、症状持续时间和包括糖尿病在内的结核病的危险因素等方面均无差异(20.0与14.0%,分别;p = 0.387; data not shown), between the steroid-use and non-use groups. There were no significant differences in severity indices (such as the oxygenation ratio), shock unrelated to sepsis, septic shock and MOF between the two groups. Corticosteroids did not affect either the duration of mechanical ventilation (p = 0.603) or oxygenation ratio (arterial oxygen tension/inspiratory oxygen fraction), measured on the seventh day of steroid therapy (p = 0.182; data not shown).
讨论
在一个国家结核病的中间负担(2005年73.0案件每10万总人口)进行本研究23艾滋病毒感染率低(1985年至2004年期间艾滋病毒感染的累计发病率为4,700万人中的3,153人)24而且,据目前作者所知,这是最大的一项调查ARF合并结核病病例的研究。
在抗结核药物开发的当前阶段,由于结核病而产生的ARF已变得相对罕见。然而,结核病仍然是严重的社区获得性肺炎的主要原因4-6。In the present study, the mean interval from hospital admission to start of anti-TB treatment was 4.3±6.0 days. This indicates a somewhat shorter treatment initiation interval than in other studies (14.9 days6and 7.2 days25)。可能的原因是,当韩国医生检查病人使用任何表现不典型,TB总是怀疑,因为仍有结核病在韩国发病率相对较高,和医疗专业人员都知道,TB可以有不同的表现形式。总死亡率在本研究中为65.6%(59个90),其类似于先前报道的那些(66-81%)4-6。当它被认为是大多数的患者处方抗结核治疗后立即入场,而大多数情况下,有非MDR-TB不合并HIV,死亡率高。
在许多以前的报告中,MTB被认定为ARF或急性呼吸窘迫综合征的主要病因22-28。MTB患者更容易发展需要机械通气的ARF,一些MTB患者最初在胸部x线片上表现为间质浸润而非粟粒样改变,导致延误诊断五。在本研究中,有83.3%的MTB患者报告有ARDS,但这一结果可能存在偏倚。在以前的报告中,尽管一些患者的临床和影像学特征与急性呼吸窘迫综合征(ARDS)相一致,但组织学显示合并结核性支气管肺炎,没有急性呼吸窘迫综合征的证据29。
相较于MTB,TBP很少被认定为急性肾功能衰竭的原因19,30.。由于ARF的病因是TBP和严重细菌性肺炎,在放射学上很难区分,这意味着准确的诊断可能会延迟。在本研究中,TBP组从入院到开始抗结核治疗的平均间隔时间长于MTB组(分别为5.0±7.0天和2.8±2.5天)。区分结核病与其他传染病的最重要因素是入院前症状持续时间较长19。In the present study, the mean duration of symptoms before admission (29±28 days) was similar to those reported in previous studies19,31。因此,对结核病合并严重肺炎的患者,特别是在流行地区,应定期进行AFB痰检。
调节的严重炎症反应的有害影响皮质激素的使用还没有重症结核引起的呼吸衰竭进行前瞻性研究。然而,一些医生处方类固醇时的结核病灶是严重的和渐进的。埃布斯等。30.报道称,ARDS在十分之七的58 TB-与-ARF患者发展;类固醇在所有七个情况下使用。背风处等。6另据报道,在25个41 TB-与-ARF患者发展为急性呼吸窘迫综合征;13out of 25 patients received >2 mg·kg-1·天-1ARDS发病的纤维增生阶段的治疗后甲泼尼龙第七天。在TBP的管理与ARF皮质激素的有益效果是由几个报告建议。首先,分枝杆菌抗原可诱导单核细胞的热原的释放,从具体致敏淋巴细胞和细胞因子,如肿瘤坏死因子,巨噬细胞和外周血单核细胞,淋巴因子,其可以负责全身症状和组织损伤32。皮质类固醇可以抑制淋巴因子和细胞因子的释放和活动。其次,TB肉芽肿宿主反应可矛盾的是保护隔离结核分枝杆菌从抗结核治疗。佐剂的皮质类固醇可以是允许抗结核药有益渗入肉芽肿,通过破坏肉芽肿形成33。
其中TBP患者中,那些接受类固醇治疗表现出平均死亡率低。然而,这可能是一种伴随现象;的数据是不够强以允许的结论是类固醇可以是在TBP患者是有用的。在本研究中,全身使用皮质类固醇是在主治医生的决定和/或患者的基本条件完全根据。使用糖皮质激素不正式。The presence of ARDS was more frequent in steroid-use patients than in non-use patients (80 and 44%, respectively; p = 0.003), suggesting that the presence of ARDS may be part of the decision-making process when corticosteroids are prescribed. A history of previous TB may have influenced a decision not to prescribe steroids even though the frequencies of TB history did not differ significantly between the steroid-use and non-use groups (13.3与33.3%,分别;p = 0.059). A number of patients were already immunosuppressed or had other chronic diseases, and these findings may have prevented attending doctors from prescribing corticosteroids. Such patients, denied prescribing corticosteroids because of additional underlying diagnoses, may have had worse outcomes. When a positive bias for prescribing steroids was sought, it was observed, for example, that six patients were given steroids in order to relieve exacerbations of COPD but not to ameliorate the severity of the TB本身。可以想象,这些患者更有可能因为潜在的肺部疾病而发展为呼吸衰竭,尽管他们的结核病没有其他人那么严重,而且确实更有可能生存下来。
在MTB组,皮质类固醇治疗没有提高生存率;然而,这个结果是不确定的,因为样本量小。在MTB患者中使用辅助糖皮质激素是否有益尚不清楚,因为只有有限的证据和相互矛盾的结果。在一项研究中观察到有益的反应34,但这样的好处没有记录在另一个35。
本研究有一些固有的回顾性研究的局限性;一些未记录偏压可以存在。即使患者大量被列入过的很长一段时间,并进行多因素分析,数据不允许最终结论关于结核病的急性肾功能衰竭的治疗最好要绘制。此外,的MTB组中的受试者数量少降低了这些患者的分析的统计力量。在TB使用皮质类固醇与ARF,可能的正或为类固醇使用负偏压(如前所述)的情况下,防止被达成的明确的结论皮质激素可能是有用的。这样的话,即使生存率为类固醇使用组比不使用组高,而使用类固醇是生存多因素分析有利的预测。
总之,虽然韩国医生通常认为结核病是严重的社区获得性肺炎,并开始抗痨治疗的原因及时,死亡率仍然很高。独立与结核性肺炎组死亡率有关的因素是高龄和休克的存在无关败血症。尽管多变量分析显示,结核性肺炎病人使用皮质类固醇是降低死亡率的有利预后因素,回顾性研究设计防止结论,糖皮质激素可能是治疗结核性肺炎病例的急性呼吸衰竭有用。进一步的随机对照试验,有必要澄清急性呼吸衰竭的皮质类固醇在结核性肺炎管理中的作用。
利益声明
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- 收到了2007年7月1日。
- 公认2008年6月14日。
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