2. 吉林大学第一医院发育行为儿科, 吉林 长春 130021
有创机械通气可使急性呼吸衰竭患儿得到有效的呼吸支持,为挽救其生命争取宝贵的救治时间,可以显著降低其病死率。然而危重症患儿机械通气支持并不是治疗终点,最终目的是使患儿成功拔除气管插管。然而,无论是成人还是儿童都存在拔管失败的风险。一般将拔管后48 h内再次插管定义为拔管失败[1]。拔管失败与延迟撤机、ICU住院时间延长、呼吸机相关性肺炎及病死率增加相关[2-3]。成人拔管失败发生率约为17%~19%,早产儿为22%~28%,新生儿及儿童为16.3%[4]。拔管前如何进行有效的评估十分重要。在成人研究中,最大吸气压力(maximal inspiratory pressure, MIP)、浅快呼吸指数(rapid shallow breathing index, RSBI)、咳嗽峰流速(cough peak flow, CPF)、肺容量、膈肌功能评估等指标对于拔管结局具有较好的预测价值[5-6];然而在预测儿童拔管结局的指标循证医学证据尚不充分,2017年欧洲儿童机械通气专家共识中也未对拔管预测指标进行级别推荐[7]。本文就目前儿童拔管结局预测指标的有效性研究做一总结。
1 机械通气测量指标 1.1 RSBIRSBI是成人预测拔管结局最常用的一项指标,它是指呼吸频率(次/min,bpm)与自主呼吸潮气量(升,L)的比值,该指标常在自主呼吸试验中测量。RSBI越高提示呼吸肌耐力越差。当RSBI < 105 bpm/L时预测拔管成功的敏感性为97%,特异性为64%[8]。由于不同年龄儿童呼吸频率及潮气量差异较大,因此儿童的RSBI一般应用呼吸频率(bpm)/每理想公斤体重(ideal body weight, IBW)潮气量(毫升每公斤体重,mL/kg)来表示。有研究显示,RSBI < 8 bpm/(mL · kg)对于预测拔管成功的敏感性为83%,特异性为53%[9]。Saikia等[10]研究发现,拔管失败组患儿的RSBI值明显高于拔管成功组。苏小燕等[11]对132名儿童重症监护室(PICU)患儿进行拔管分析发现,自主呼吸试验前后RSBI的变化值对于判断拔管成功具有较好的预测价值。然而这一指标在儿童中预测参考值还缺乏大规模、多中心的研究来界定。
1.2 MIPMIP是在气道闭合状态下做最大吸气努力,维持至少1 s产生的最大负压。MIP由膈肌和辅助呼吸肌共同作用的结果,因此MIP可以较好反映儿童呼吸肌功能[12-14]。呼吸肌功能障碍,尤其是膈肌功能障碍与拔管失败密切相关[15]。Chen[16]对机械通气的新生儿进行拔管研究发现,MIP绝对值大于35 cm H2O对拔管成功具有良好的预测价值。测量机械通气患者的MIP过程简单易行,但需要患者配合检查者做努力吸气的动作,因此成人和认知功能较好的年长患儿测得的MIP可信度较高。而这种测量方法在低龄段患儿当中较难实现。Harikumar等[17]研究发现,对于机械通气儿童按住呼气保持键维持12 s或8个呼吸周期,最后测得的MIP可以较好地反映呼吸肌功能。然而MIP反映的是所有呼吸肌共同作用结果,部分膈肌功能障碍的患者由于辅助呼吸肌代偿作用较强,MIP未显著下降,故MIP预测拔管成功的特异性欠佳(7%~69%)[18]。因此有学者提出持续最大吸气压(sustained maximal inspiratory pressure, SMIP)的概念。SMIP是指MIP与最大持续吸气时间的乘积,是测量患者从残气量到肺总量过程中产生的压力。目前有研究显示SMIP在判断拔管上较MIP有更好的特异性和敏感性,SMIP > 57.5 cm H2O时,拔管成功率更高[19]。
1.3 呼吸功生理呼吸功(work of breathing, WOB)是肺及胸廓吸气产生形变时所做的功。而机械通气的患者在吸气时还需要克服呼吸机环路的阻力做功,这部分的WOB为附加WOB,因此机械通气患者的总WOB=生理WOB+附加WOB。WOB是通过带有压力探头的食道管测量压力-容积曲线的面积得出的,该指标对于拔管结局预测价值目前存在一定争议。Levy等[20]研究认为WOB升高(> 8 J/L)与拔管失败无关。然而该研究的局限性在于纳入样本(n=14)中只有1例再次插管,而且附加WOB的影响因素未被考虑进去。Teixeira等[21]对51名机械通气患者行自主呼吸试验期间进行WOB监测,结果发现拔管失败组的患者WOB明显增加,提示WOB对于自主呼吸试验90 min以上的患者具有预测拔管结局的价值。Banner等[22]研究显示,与MIP、RSBI相比,WOB预测拔管成功具有更好的特异性。
1.4 气道闭合压呼吸驱动力对于拔管结局的影响十分重要,过高或过低的呼吸驱动力都会增加拔管失败的风险,引起肺及膈肌的损伤[23-24]。然而测量呼吸驱动力的设备较少。40年前有学者提出一种简单的无创测量方法,即测量气道闭合压(P0.1)。P0.1指气道闭合100 ms后产生的压力。目前大多数的有创呼吸机均可进行P0.1的测量。近年来P0.1越来越多用于拔管结局的预测。有研究显示,在自主呼吸试验时P0.1 > 6 cm H2O拔管失败率更高[25]。由于不同年龄的儿童呼吸驱动力差异较大,因此采用MIP矫正后的P0.1(P0.1/MIP)可提高预测拔管结局的准确性。Nemer等[26]研究显示当患者P0.1/MIP < 0.14时拔管成功率更高。
2 膈肌评估 2.1 膈肌电活动肌肉收缩产生的电活动可以被特殊装置监测到。同样,膈肌收缩也可产生电信号,目前对于膈肌电信号(electrical activity of the diaphragm, EAdi)监测的主要方法为神经调节辅助通气技术(neurally adjusted ventilator assist, NAVA)。该技术最先应用于监测新生儿呼吸中枢驱动力。有研究显示,新生儿的呼吸中枢驱动力及膈肌力量是拔管成功的主要决定性因素[27]。Amin等[28]研究结果显示,与传统拔管评估指标相比,通过EAdi指导可以增加先天性膈疝术后患儿拔管成功率。法国一项多中心随机试验结果显示,与传统压力支持通气(PSV)模式比较,NAVA组患者拔管成功率更高,拔管后的无创通气使用率及病死率明显低于PSV组[29]。Koyama等[30]对EAdi与MIP进行比较发现,肌无力患者应用EAdi预测拔管结局较MIP具有更高的信度;Wolf等[31]对20例机械通气患儿拔管前进行EAdi检查,结果显示EAdi和潮气量与拔管成功率呈正相关,且EAdi可以较好地反映机械通气患儿的呼吸中枢驱动能力。但获取EAdi信号需要插入胃管,属于侵入性检查,此外膈肌电信号还受食管、心脏等器官信号的干扰,因此目前在临床没有进行常规开展。
2.2 膈肌超声超声技术能直接观察到膈肌活动,并且具有无创、便捷等优势。膈肌超声可以较好地反映膈肌真实的功能状态,对于儿童膈肌功能的监测同样具有较好的信度[32]。机械通气患者常用的超声监测值为膈肌增厚分数(diaphragmatic thickening fraction, DTF)。DTF计算方法为(吸气末厚度-呼气末厚度)/呼气末厚度×100%,当DTF < 20%时诊断为膈肌功能障碍[33]。DTF > 30%对预测拔管成功的敏感性为88%,特异性为71%[34]。目前对于膈肌功能评定的金标准为跨膈压。Dubé等[35]将膈肌超声监测的DTF与跨膈压比较发现,二者呈高度正相关,提示DTF可较好地反映膈肌功能进而预测拔管结局。Glau等[36]对56名机械通气患儿行膈肌超声检查发现,膈肌萎缩与撤机困难及拔管失败具有相关性。Llamas-Álvarez等[37]进行的一项Meta分析纳入了19项研究,结果显示膈肌超声可以很好预测拔管结局,但其准确性会受到操作者的影响。Farghaly等[38]研究结果同样证实膈肌超声在预测机械通气患者拔管结局方面具有较好的特异性和敏感性。目前膈肌超声在成人拔管预测研究较多,但在儿童方面的研究却较少,未来可能会成为儿童撤机拔管研究方向的重点。
2.3 膈肌张力-时间指数膈肌张力-时间指数(tension-time index of the diaphragm, TTdi)是评估膈肌能力最佳的指标,被认为是决定拔管结局的重要因素。TTdi的计算方法为每次呼吸的平均跨膈压与最大跨膈压之比乘以吸气时间与总呼吸周期时间之比。当TTdi > 0.15时拔管失败的可能性更大[39]。部分研究结果显示TTdi在预测儿童拔管成功的敏感性及特异性可达100%[40-41]。Harikumar等[42]对80名机械通气儿童进行拔管前评估,结果显示与顺应性-呼吸频率-氧合-压力指数、RSBI等指标相比,TTdi具有更高的敏感性和特异性。其局限性同样为侵入性检查,存在有创及费用高等缺点,因此未在临床当中常规应用。
3 上气道通畅性评估 3.1 漏气试验上气道梗阻(upper airway obstruction, UAO)是引起儿童拔管失败的最常见原因之一,而二次插管、困难气道、延迟机械通气的患者拔管后UAO的发生率更高[43],拔管后UAO发生率为1.5%~26.3%[44]。因此上气道通畅性的评估对于预测拔管结局十分重要,目前常采用气囊漏气试验。气囊漏气试验方法为在容量控制通气下,气囊充盈和塌陷时分别测定呼出潮气量,并计算两者差值。通常认为气囊漏气试验结果的正常范围,成人为88~140 mL(110 mL最常见)或10%~15.5%(15.5%最常见)[45]。然而儿童的潮气量不同年龄差异较大,因此更适合计算漏气前后百分比的变化。目前对于漏气试验预测UAO存在一定争议。有研究显示当漏气试验结果为0 mL时,预测UAO的敏感性为86%,特异性48%,阳性预测值11%,阴性预测值99%[44]。2017年美国胸科协会等制定的临床实践指南指出,对于机械通气具有UAO高危因素的患者建议拔管前行气囊漏气试验[46]。Schnell等[47]研究结果显示漏气试验对于预测UAO的假阳性率较高,可能会导致不必要的机械通气时间延长。Wang等[48]认为漏气试验的价值有限,其对预测拔管成功的特异性较好,而敏感性较差,同时常规进行漏气试验会增加呼吸机相关性肺炎发生的风险。
4 气道保护能力评估 4.1 CPF评估机械通气患者的气道保护能力对于预测拔管结局十分重要。咳嗽能力是反映气道保护能力的常用指标。临床上常采用CPF反映患者的咳嗽能力。采用CPF预测拔管结局具有很好的特异性和敏感性。当CPF≤60 L/min时拔管失败率是CPF > 60 L/min的5倍[49];CPF≤60 L/min、61~89 L/min、≥90 L/min者再插管的发生率分别为29.4%,16.7%和1.9%[50]。Duan等[51]研究显示,CPF≤70 L/min者拔管失败率更高;Gobert等[52]对92名机械通气患者拔管前进行CPF及肺活量评估,结果显示,CPF及肺活量联合预测拔管成功率可达94.2%。以往机械通气患者测量CPF需在人工气道开口处连接呼吸流量仪测量,然而此方法需断开呼吸机,操作较繁琐。目前常用的方法是通过呼吸机上的流速-时间曲线观察CPF。Bai等[53]研究显示,与流量仪相比,用呼吸机测量CPF同样可有效预测拔管结局。Duan等[54]对186名患者进行拔管前评估发现,CPF与半定量咳嗽强度评分均可有效预测拔管失败风险。
4.2 格拉斯哥评分意识障碍患者多数伴有气道保护能力下降,而气道保护能力可影响拔管结局,因此意识障碍严重程度的评估对于预测拔管结局同样重要。目前对于意识障碍程度评估常采用格拉斯哥评分(Glasgow Coma Scale, GCS)。Godet等[55]研究显示,与GCS评分 < 8分相比,GCS评分≥8分拔管成功率更高。Ayubi等[56]研究结果显示,GCS评分 < 5分患者拔管失率高达46.5%。Kutchak等[57]对132名机械通气患者进行拔管结局比较发现,拔管成功患者的GCS评分明显高于拔管失败患者。Guru等[58]发现当患者的GCS评分≤6分拔管失败发生率更高,可能需要气管切开。Asehnoune等[59]对437名颅脑损伤患者进行拔管因素分析发现,GCS评分 > 10分对拔管成功具有较高的预测价值。但是对于气管插管的患者由于不能准确评估语言得分,因此评估分值可能会小于实际得分,导致部分患者拔管延迟。
5 气道保护能力评估拔管准备试验(extubation readiness tests, ERTs)是近年来广泛应用在PICU当中的一种拔管前评估方法[60]。ERTs主要可以帮助检查者确定已具备拔管指征的患儿。大多数ERTs检查者会给予保证患儿SPO2 > 95%、潮气量 > 5 mL/IBW时的最低呼吸机支持(FiO2 < 50%、PEEP 5 cm H2O),观察2 h内患儿有无窒息或氧合下降等情况发生。耐受ERTs患儿拔管成功率为87%[61]。Foronda等[62]研究结果显示,与经验性拔管相比,每日ERTs评估可以减少患儿机械通气时间,并增加拔管成功率。Shalish等[63]进行的一项Meta分析结果表明,在预测早产儿拔管失败方面,ERTs比经验性拔管具有更高的敏感性。然而对于一个日常工作极其忙碌的PICU单元,医生很难进行每日的ERTs,因此呼吸治疗师在ERTs中的作用尤为重要。Abu-Sultaneh等[64]对398名机械通气患儿拔管前行ERTs,结果表明与医生评估相比,由呼吸治疗师指导的ERTs拔管失败率由7.8%降至4.5%。虽然ERTs可有效减低拔管失败风险,但目前还尚未建立标准的ERTs流程。此外,并不是所有的PICU单元都有相应的呼吸治疗团队。上述因素会影响ERTs预测拔管结局的准确性。因此如何规范ERTs流程是儿童重症医学领域的研究重点。
总之,目前对于有创机械通气患儿拔管前评估尚缺乏敏感性和特异性均佳的指标,各项研究还处于小样本、单中心阶段,临床指南当中也未对上述指标进行级别推荐。机械通气儿童拔管评估实际是一个多学科的评估。疾病严重程度、意识状态、呼吸肌功能评估、气道保护能力等因素均与拔管结局密切相关,因此如何优化机械通气儿童拔管前的评估,提高拔管成功率是PICU及康复科医生共同努力的方向。
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