抽象
本多中心研究的目的是评估相当与家庭机械通气(HMV)相关的利益和负担。
使用医疗结果研究36项简短健康调查(SF-36;一般HRQL)和严重呼吸功能不全(SRI)问卷(条件特异性HRQL)。
总共,85(27慢性阻塞性肺病,29限制性胸椎,17神经肌肉,九名肥胖低通气综合征和三个杂)的135周符合条件的患者完成了研究。平均值±SD85例患者的SRI综合量表(范围为0-100)从基线的49±15,到1个月的61±15,到1年的61±16,均有显著改善,但亚量表得分的改善在各亚组之间存在差异。SF-36评分也有所提高,但SRI在检测HRQL变化方面更胜一筹。面部疼痛和喉咙干燥是最常见的副作用。患者花费的平均值±SD基线住院12±6天,每次随访3±3天。只有4名患者需要进行计划外住院治疗。
在独立于基础疾病的家庭机械通气设施建立后,总体上一般和特定情况下与健康相关的生活质量方面得到改善,但这对特定健康相关生活质量领域的变化有影响。一旦家庭机械通风系统被仔细地建立起来,住院的必要性就会降低。
无创正压通气(Noninvasive positive pressure ventilation, NPPV)越来越多地用于治疗由各种基础疾病引起的慢性肺泡低通气(CAH),如限制性胸廓疾病(RTD)、神经肌肉疾病(NMD)、肥胖低通气综合征(OHS)和慢性阻塞性肺病(COPD)。1,2。绝大多数接受终生NPPV作为家庭机械通气(HMV)的CAH患者是不可能愈合的。这些患者通常患有终末期疾病,在日常生活中客观上有严重的局限性。因此,评估主观报告的健康相关生活质量(HRQL)在这些重病患者是极其重要的。
在临床试验中,问卷是评估HRQL最常见的形式。针对疾病或情况的问卷被认为比一般问卷对变化更敏感,因此最适合评估具体治疗干预措施的临床试验3。然而,有,仍有约HMV如何在CAH患者影响HRQL的不确定性。近日,在国内机械通气研究组的生活质量已经开发出了严重的呼吸功能不全(SRI)的问卷调查,经过专门设计,以衡量HRQL在接受HMV患者4。这份问卷已被证明具有较高的心理特性4和能够检测以下各种疾病建立HMV的HRQL变化五,6。因此,SRI似乎是临床试验的患者在HMV正在建立CAH的不同病因,旨在评估HRQL适当的工具。
有越来越多的证据表明,整体HRQL强烈,业已接受HMV,用最好的HRQL患者基础疾病的影响在侧后患者被报道在COPD最差4,7,8。虽然不存在患者的RTD和NMD对照研究中,HRQL被认为是大幅增加在这些患者同时HMV正在制定7,9。相比之下,纵向研究只记录了COPD患者HMV后HRQL的轻微和不一致的改善10-14。因此,有人建议HRQL的由HMV获得的效益各种底层病症之间不同。然而,这个从未在一个定量的方式解决。
本多中心研究的目的是测试一个HRQL的一般和条件具体方面改进后,采用HMV的假说。此外,有人假设,改进将根据潜在病症不同。最后,负担所造成的HMV对于住院和副作用也评估。
方法
目前的研究方案经在阿尔伯特 - 路德维希大学(德国弗莱堡),并通过所有参与机构的当地伦理委员会人类研究机构审查委员会,并根据宣言所规定的道德标准进行赫尔辛基,从所有受试者获得2000处获悉,书面同意。
患者和研究设计
COPD是按照国际准则诊断15。只有谁住院进行择HMV设立专门为无创正压通气病房NPPV初治和稳定的CAH患者连续参加。入选标准是从国际准则采用16。因此,所有包括患者CAH的症状,如疲劳,呼吸困难和早晨头痛,除了由指南确定生理条件16。急性呼吸衰竭(pH值<7.35和/或两个的标准如下:增加咳嗽;脓痰;升高的白细胞或C-反应蛋白> 5mg的·dL的-1;胸片肺部浸润;或需要进行抗生素治疗),那些谁获得创通气通过排除气管造口、前3个月转离有创通气或插管者,以及本研究前接受其他通气支持(包括持续气道正压)者。最后,在建立“HMV”的医院就诊时药物治疗有任何变化的患者也被排除在外。
Assessments were performed prior to HMV establishment in hospital, with follow-up checks occurring during short hospitalisation periods, 1 and 12 months after the establishment of HMV. No planned control visits were performed between 1 and 12 months. Duration of hospital stay was assessed for planned hospitalisation prior to HMV and at 1 and 12 months, and also for unplanned hospitalisations.
患者接受辅助/控制NPPV旨在最大限度减少二氧化碳动脉张力(P,有限公司2)最好的耐受性可能五,17,18。简单地说,NPPV滴定,直到血碳酸正常达到或直到设置的进一步增加并不患者耐受逐渐增加的呼吸机参数,实现被动通风。小心地使患者舒适。如有必要,加湿使用。此外,工厂制造的鼻面罩被使用,但患者在重大泄漏或通风不良的情况下被切换到工厂制造的鼻口口罩。最后,被用于减少泄漏和使用工厂制造的口罩时,减少压疮单独建口罩。符合HMV评估通过访谈患者并通过呼吸机计数器阅读所有患者。不服从被定义为由于不愿意继续而停止HMV。此外,医生记录了NPPV在1个月和12个月引起的副作用,患者的反应是“是”或“不是”。HRQL在HMV前、1个月和12个月进行评估。
除测量肺功能外,还测量日间从已动脉化的耳垂采集的血气19and mouth occlusion pressures prior to HMV and at 1 and 12 months. For maximal inspiratory mouth pressure (P我,马克斯),得到的峰值压力,如前所述20。During NPPV, further blood gas measurements were performed in the night prior to HMV and at 1 and 12 months to optimise NPPV treatment (data not shown).
医疗结果研究采用36项简短健康调查(SF-36),包括8个子量表和2个摘要指标(物理成分摘要和心理成分摘要)来评估一般健康21,22。此外,SRI问卷为HRQL的特定方面的评估管理4;在这里,可以从七个子量表构建一个总结量表。在发生HMV前、1个月和12个月进行了HRQL评估。两份问卷均适用于HMV患者的HRQL评估,并已被证明具有区分不同诊断组的能力4,8。
统计分析
平均值±SD值。相关分析采用皮尔逊积差相关。采用多变量方差分析来检验时间效应和组效应(例如诊断)对因变量(例如HRQL数据,生理参数)。对于HRQL,三个摘要秤被使用:SRI-摘要规模,SF-36-PCS和SF-36-MCS。事后测试(成对和不成对t检验,这取决于比较)如果在多元方差分析总体效应<0.05进行。组的效果仅限于COPD患者,RTD及NMD,由于患者的不同的基本紊乱低案例编号。功率分析(GPower 3.0.8;在海因里希·海涅大学,杜塞尔多夫,德国实验心理学系)进行确定效果大小的亚组分析。
多变量方差分析也被用于比较完成研究的患者和那些退出。此外,在检测HRQL变化的能力方面,对SRI和SF-36量表进行了比较(多变量方差分析)。这里将z值标准化后进行计算,假设不同问卷量表的平均分值不同。p值<0.05认为有统计学意义。
结果
病人
从9个专门研究NPPV的德国中心招募了137名接受HMV的患者(图1)⇓):Evangelisches Krankenhaus哥廷根-Weende E.V.(Lenglern; n = 31), Asklepios Fachkliniken München-Gauting (Gauting; n = 23), Krankenhaus Großhansdorf (Großhansdorf; n = 22), Universitätsklinik Freiburg (Freiburg; n = 21), Krankenhaus Donaustauf (Donaustauf; n = 10), Universitätsklinik Magdeburg (Magdeburg; n = 10), Fachkrankenhaus Kloster Grafschaft/Schmallenberg (Schmallenburg; n = 8), Lungenfachklinik Heckeshorn/Berlin (Berlin; n = 6) and Städtisches Krankenhaus Martha–Maria Halle-Dölan (Halle; n = 6). Two patients were excluded and 135 patients were included (fig. 1⇓)。所有患者均在入选稳定(平均值±SDpH值7.40±0.04)。平均值±SD完成研究和未完成研究的患者的年龄具有可比性:61±11与62±9岁(COPD), 63±13岁与61±14 yrs (RTD), 53±15与64±14 yrs (NMD) and 59±6与分别为53±14年。BMI也是如此:28±9与29·m±8公斤-2(COPD), 27±6与26±5 kg·m-2(RTD),26±8与24±3公斤·m-2(NMD)和40±7与42±1 kg·m-2(OHS),分别。下面的结果是指85例谁完成了研究,如果不是另有说明。
无创正压通气
In total, 65 (76.5%) patients received pressure-limited NPPV (table 1⇓20例(23.5%)患者接受容量限制的NPPV治疗。50(59%)名患者采用了被动湿化,6(7%)名患者采用了主动湿化。共有31例(36.5%)患者在NPPV的基础上补充氧。使用接口:工厂化口罩(n = 33;39%);工厂制造的鼻口口罩(n = 9;11%);单独制作的鼻用口罩(n = 42;49%);以及单独制作的鼻口口罩(n = 1; 1%).
At 1 month (T1), patients claimed to use the ventilator 7.2±2.1 h per day, and the counter indicated 6.5±2.1 h of HMV per day (r = 0.82, p<0.001). Accordingly, 8.0±2.4 h (patient) and 7.3±2.7 h (counter) of HMV were indicated at 12 months (T12) (r = 0.86, p<0.001). Ventilator settings only slightly and nonsignificantly changed during the study period, with the exception of an increase of the inspiratory positive airway pressure in RTD and NMD patients: 20.5±3.8 (prior to HMV (T0); 2.00±0.37 kPa) to 21.5±4.0 cmH2O (T12; 2.10±0.39 kPa; p<0.05) and 19.3±4.0 (T0; 1.89±0.39 kPa) to 21.2±4.6 cmH2O (T12; 2.07±0.45 kPa; p<0.001), respectively.
生理参数
在基线生理参数并没有在病人谁完成了研究与那些谁没有比较不同。例如,平均值±SD用力呼气量一秒(FEV1)为34±14与31±15%的预测(COPD),39±14与32±11%预解码值(RTD)和49±23与48±17%的预解码值(NMD),分别;平均值±SD总肺容量(TLC)为105±30与112±22% pred (COPD), 61±17与61±17% pred (RTD)和75±24与75±11%预解码值(NMD),分别;平均值±SDP,有限公司2was 58.6±9.3 mmHg (7.79±1.24 kPa)与58.7±7.0 mmHg(7.81±0.93 kPa)51.5±8.4 mmHg(6.85±1.12 kPa)与五4。6±3.8 mmHg (7.26±0.505 kPa; RTD) and 52.4±10.4 mmHg (6.97±1.38 kPa)与49。2±14.0 mmHg (6.54±1.86 kPa; NMD), respectively; mean±SDP我,马克斯为4.2±1.4与五。4±2.5 kPa (COPD), 3.7±1.6与3。6±0.3 kPa (RTD) and 3.7±1.8与3。2±1.2 kPa (NMD), respectively. Data for OHS were missing. Baseline data are shown in table 1⇑。有肺功能参数轻微但显著上升的T12在COPD和RTD病人,但不是在NMD和OHS。FEV1pred: 34±14 ~ 41±23% (COPD;和39±14 ~ 45±15% pred (RTD;分别为p < 0.01);强迫肺活量(FVC): pred (COPD) 50±19 ~ 63±24%;p<0.001)和39±16 ~ 48±14% (RTD;分别为p < 0.01);COPD患者TLC: 105±30 ~ 114±27% pred (p<0.01), RTD变化无统计学意义。FEV1/ FVC没有显著改变。P我,马克斯COPD (RTD)患者治疗1年后kPa由4.2±1.4(3.7±1.6)kPa升高至4.9±2.3(4.6±2.0)kPa (p<0.05和p<0.01)。血气的变化见表2⇓。
住院治疗
为了熟悉NPPV,患者需要完成平均12±6天的住院时间。相比之下,在每次常规计划的对照就诊中,患者只需要在医院呆3±3天。只有4名患者需要额外的非计划住院:因COPD加重的2名患者,分别住院6天和13天;1例肌萎缩性侧索硬化症(ALS)患者的抽吸(住院2天);另一位肌萎缩性脊髓侧索硬化症患者(住院4天)的口罩问题。
HRQL
HRQL的两个一般(SF-36)和疾病特异性的(SRI)方面患者CAH HMV的机构下列改善;in the present study, HRQL had already improved following 1 month of HMV and subsequently remained stable at this elevated level during the following year (fig. 2⇓)。Multivariate ANOVA on HRQL summary scales multiplied by time revealed significant effects over time (F = 32.80, p<0.0001) and the interaction of HRQL summary scales over time (F = 11.56, p<0.0001). Multivariate ANOVA on diagnostic groups multiplied by HRQL summary scales multiplied by time revealed a significant effect over time (F = 22.22, p<0.001). However, overall differences in patient groups were not significant (F = 0.11, p = 0.89) and improvements in HRQL summary measures were not dependent on the underlying disease (F = 0.62, p = 0.65). Here, power analysis with an achieved sensitivity of 0.8 indicated that the present study could detect even small differences with effect sizes of 0.3 with regard to a middle correlation of the HRQL measures of 0.5.
相比之下,HRQL的变化与SRI和SF-36单项量表的疾病相关(表3)⇓和图4⇓)。特别是,在身体机能的改善显著只有在COPD和RTD患者明显。相反,在NMD和OHS患者中观察到伴随的症状和睡眠最改进,尽管所有其他患者改善。Importantly, improvements in psychological well-being and social functioning after 1 yr of HMV were highly significant in COPD, RTD and OHS patients, but were nonsignificant in NMD patients. All patients also showed substantial improvements in respiratory complaints and anxieties, although RTD and OHS patients had the highest increases in anxiety scores. Social relationships were the only SRI subscale in which no improvements were gained. However, this subscale already showed the highest scores, even at T0, indicating less impairment.
当SRI和SF-36的概要尺度进行比较在HRQL整体改进是不同的。Even when z-value standardisation of the scale scores was performed, the improvements gained by the summary score of the SRI were significantly more evident when compared with the PCS of the SF-36 (multivariate ANOVA: F = 2.60, p = 0.037). Although both summary measures of the SF-36 improved significantly in the total group (n = 85) of patients (fig. 2⇑), this was not valid for the single groups of patients (table 3⇑)。此外,在这三个不同患者组SF-36分量表得分的改善是不一致的,与八个,四和一个分量表分别表示RTD,COPD和NMD患者在T12的改进,。
For both the summary measures of the SF-36 and the summary score of the SRI at baseline (T0), no significant differences in scores could be detected between patients who completed the 1-yr follow-up (n = 85) and those who did not (n = 50). In addition, patients who discontinued after T1 (n = 37) had comparable improvements in the SRI summary score and the summary measures of the SF-36 between T0 and T1 compared with those who completed the study (n = 85; multivariate ANOVA: F = 0.38, p = 0.69).
无创正压通气的副作用
患者最常见的副作用为T1谁完成的研究中所造成的面具(33%),面部疼痛和喉咙干(37%)。However, only 25 and 26% of patients who completed the study reported facial soreness and dry throat at 12 months, respectively. Side-effects of NPPV for all patients are shown in table 5⇓。甲咽干既在COPD患者的最频繁报道的症状(46和分别在T1和T12,29%)和在NMD患者(分别为47和在T1和T12 18%)。与此相反,鼻充血是RTD患者(分别为T1和T12 31和21%),最常见的症状。副作用也没有谁T1后辍学与谁完成了研究比较了患者尤为存在。
讨论
本研究的主要发现是,HRQL的一般和条件的具体方面增加了以下HMV建立。Importantly, substantial improvements were gained 1 month following HMV establishment, and these improvements could be maintained for the subsequent 12 months, during which time HMV was continued.
总体改善是慢性阻塞性肺病,RTD和NMD患者之间相似。特别是,COPD患者与那些患者的RTD和NMD由HMV获得整体HRQL利益。这是没有事先预测。对于患者RTD和NMD,有压倒性的证据表明,生理参数,睡眠质量,HRQL,甚至生存,都是可以由HMV得到改善1,7,9,16。相比之下,只有在生理参数和HRQL上的不一致的改善被记录下来,并且对于HMV在慢性高碳酸血症的COPD中潜在的生存益处还没有明确的证据7,10-14,16,23-26。因此,目前的研究是在证明这两个血液气体和整体HRQL COPD患者和在那些与限制性疾病相对提高唯一的。一个区别与以往的研究相比,是无创通气的目的是最大限度地减少P,有限公司2通过使用相当高的呼吸机参数,如先前所建立五,17,18。在下拉P,有限公司2甚至在COPD患者更为明显,这是由于较高的值之前,HMV在COPD。因此,它是合理的建议,这是针对朝最大限度地提高肺泡通气使用NPPV的,导致了物理参数和COPD患者的整体健康相关生存质量的改善相媲美,与严格的患者相比。
与在HRQL总体改进,变化在HRQL的单一的,特定结构域对于SRI分量表差异显著取决于潜在的疾病。呼吸道症状在所有患者只有在和,少显然,在OHS患者,而得分在NMD保持稳定,这可能是由于COPD患者,RTD显著上升,但是这导致了改善身体功能和社会功能的得分成绩差点伴随呼吸功能障碍,即四肢无力。相反,伴随症状和睡眠得分的改善在NMD和OHS患者中最为显著,但在心理健康得分的改善在COPD和RTD患者中更为明显。此外,所有患者的焦虑得分均有显著改善,但RTD患者似乎获益最大。这清楚地表明,CAH的发展对HMV建立后HRQL特定方面的变化有重大影响。然而,由于所有患者的亚量表呼吸不适、伴随症状和睡眠评分均有显著改善,这表明一旦建立了HMV,与夜间低通气相关的症状得到改善。
本研究的另一个重要的发现是,SRI是检测HRQL变化优于SF-36。虽然SF-36的两个综合性指标揭示的分数总组显著增加,这是不是对患者的单组真实的。这是在对比的是SRI,在总结成绩的规模不仅总组中,而且在单组增加。In addition, improvements of SF-36 subscale scores were inconsistent, with eight, four and only one subscales showing improvements following 1 yr of HMV in RTD, COPD and NMD patients, respectively. Therefore, looking solely at the SF-36, HRQL benefits gained by HMV appeared to be quite small in patients with NMD compared with other patients, particularly those with RTD. However, administration of the SRI also revealed substantial improvements in overall HRQL in NMD patients compared with other disease categories. This underlines the inalienability of disease- or condition-specific instruments for reliably assessing changes in HRQL in a particular group of patients using specific treatment modalities, as in those with CAH receiving HMV. The language of the original SRI is German. However, results of the Spanish version have recently been published27英语、荷兰语、法语、瑞典语和挪威语的其他版本正在编写中(M.W. Elliott(英国利兹圣詹姆斯大学医院呼吸内科);P. Wijkstra(荷兰格罗宁根大学医院);A. Cuvelier(鲁昂大学医院肺和重症监护室,鲁昂,法国);B. Midgren(瑞典隆德大学医院呼吸内科);H. Markussen(挪威卑尔根豪克兰大学医院);个人沟通),以使SRI在国际上可用。
On average, 12 days in hospital were needed for patients to become familiarised with NPPV, and this might be related to the effort required to optimally improve blood gases and to optimise comfort during NPPV using high ventilator settings as suggested by previous investigations13,17。In contrast, only 3 days in hospital were necessary for control visits in patients who continued HMV for 1 yr, and only four (<5%) of these patients required additional, unplanned hospitalisation following careful HMV establishment. Nevertheless, the duration of the initial hospitalisation period might be judged as rather long, despite low hospitalisation duration following HMV commencement, and further studies should evaluate if shorter periods in hospital are comparably sufficient when initiating HMV. In addition, comparison of hospitalisation with the preceding year was not possible in the present study, but previous studies showed that in COPD patients the establishment of HMV resulted in fewer days in hospital and fewer hospital admissions14,28。
最常见的副作用为咽喉干燥,疼痛脸,鼻塞和腹部问题,这支持了以前的研究结果1,29。虽然慢性阻塞性肺病和NMD患者最常报告的一嗓子发干,而RTD最患者常主诉鼻塞,没有关于副作用的患者群体之间没有明显的差异。In addition, not falling asleep and sleep disruption were reported by 16 and 20% of patients after 1 yr of HMV, respectively. Although scores of the SRI subscale attendant symptoms and sleep dramatically improved, particularly in NMD and OHS patients, HMV could not completely erase subjectively experienced impairments in sleep quality, or might even have caused some degree of subjective discomfort during the night. This is supported by previous sleep studies, which have clearly shown that sleep quality assessed by polysomnography was significantly improved by HMV, but did not become completely normalised6,24,三十,31。然而,之间的联系,客观地记录和报道的主观睡眠质量需要进一步调查。
有迹象表明,需要解决当前研究的一些限制。首先,额外的患者没有随机分为对照组。然而,有对符合HMV,这是在改善血气高效清晰的证据,这是不可能的,这可能不HMV来实现。因此,HRQL利益很可能主要是由于HMV。In addition, blinding of patients and implementation of sham ventilation for a period of 1 yr are extremely difficult to achieve. Moreover, controlled studies would raise ethical concerns, at least in patients with RTD and NMD, given the overwhelming evidence that HMV is indeed beneficial for these patients. Nevertheless, controlled studies in COPD patients are clearly needed to overcome the weaknesses of the uncontrolled study design.
其次,它也可能会被认为有选择偏倚。然而,患者连续参加,这可能解释了相对较高的辍学率。In addition, patients who dropped out and those who completed had comparable demographics, physiological parameters and HRQL prior to HMV, and also had comparable HRQL improvements after 1 month of HMV. Therefore, a clear selection bias seems unlikely. In addition, a large number of statistical tests have been executed and false-positive results cannot be excluded with certainty.
第三,本研究旨在进行亚组分析,但亚组存在一定的异质性,NMD患者尤其如此。因此,这一组的结果可能不容易转移到每一特定类型的NMD,需要进一步的研究来比较评估不同明确的NMD患者组,特别是ALS患者中hmv诱导的HRQL变化。此外,形成OHS组的患者人数太少,无法纳入多元方差分析。因此,HRQL的变化不能与其他潜在疾病的变化进行比较。最后,需要进一步的研究来确定HRQL对大多数晚期疾病的益处是否最明显,以及轻度CAH患者是否完全受益。
总之,目前的研究表明,家用机械通气时仔细成立于医院,旨在最大限度地改善血气,似乎是能够显着改善生活的健康质量的一般和具体条件方面,从患者慢性肺泡通气不足,有副作用的是与那些在以往的研究报道。一旦家机械通气在医院精心建立起来,需要进一步住院治疗低。在生活的健康质量总体改善是慢性阻塞性肺疾病,限制性胸部疾病和神经肌肉疾病相媲美。与此相反,生活的变化与健康相关的质量显著诊断组之间的几个特定的结构域不同,表示潜在的疾病上的生活的变化健康相关的质量的影响。在严重呼吸功能不全问卷,专门针对病人谁是依赖于家庭机械通气,是当与一般仪器医疗结果研究36项短形式的健康调查相比,检测生命健康相关的质量变化优越。这凸显了疾病或病症特异性仪器可靠地评估患者接受家庭机械通气生命健康相关的质量变化的不可剥夺。
利益声明
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致谢
家庭机械通气生活质量研究组(全德国)成员如下:T. Barchfeld (Fachkrankenhaus Kloster Grafschaft/Schmallenberg, Schmallenberg), K. Freidel(统计学家;威斯巴登圣josefs医院,J. Geiseler (Asklepios Fachkliniken Munchen-Gauting, Gauting), F. Heinemann (Donaustauf, Donaustauf), F. Kalbitz (Stadtisches Krankenhaus marta - maria Halle- dolan, Halle), T. Kohnlein(马格德堡大学,马格德堡),M. Raffenberg (Lungenfachklinik Heckeshorn/柏林,柏林),F. Petermann(不莱梅大学,不莱梅),K. Schild (Ev。Krankenhaus Gottingen-Weende e.V., Lenglern), B. Schucher (Krankenhaus Gro because hansdorf, Gro because hansdorf)和W. Windisch (Freiburg university, Freiburg)。
笔者衷心感谢S. Dieni校对稿子之前提交。
- 收到了2007年6月2日。
- 公认2008年6月16日。
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