Abstract
目的
探讨反比通气（IRV）联合呼气末正压（PEEP）对单肺通气（OLV）时肺囊腺瘤术婴儿的影响。
方法
选择2018年2月~ 2019年2月于广东省妇幼保健院择期行胸腔镜下肺囊腺瘤手术单肺通气的婴儿患儿66例，随机分为常规通气组（N组，n=33）和反比通气组（R组，n=33）。记录双肺通气（TLV）15 min（T1）、OLV30 min（T2）、OLV60 min（T3）、恢复TLV15 min（T4）患儿的血流动力学和呼吸参数，并进行动脉血气分析。于术前和术后行支气管灌洗，并收集支气管灌洗液，检测晚期糖基化终末产物受体（RAGE）的表达水平。
结果
共63例婴儿最终入选。在T2、T3时点，R组Cdyn、PaO2、OI显著高于N组同时间点（P < 0.05），气道峰压、动脉二氧化碳分压（PaCO2）、动脉血氧分压（PaO2）显著低于N组同时间点（P < 0.05）。T2、T3时间点的HR和MAP两组间比较差异无统计学意义（P > 0.05）。两组术后RAGE与同组术前相比都明显增高（P < 0.05），而术后与N组相比，R组的RAGE表达水平较低（P < 0.05）。
结论
合适的IRV联合PEEP应用于胸腔镜下肺囊腺瘤术的OLV婴儿患者，既不影响血流动力学稳定，同时能增加肺顺应性，降低峰压，改善氧合，安全可行，有一定的肺保护作用。
Keywords: 反比通气, 呼气末正压, 单肺通气, 婴儿, 肺囊腺瘤
Abstract
Objective
To investigate the effect of inverse ratio ventilation (IRV) combined with positive end-expiratory pressure (PEEP) in infants undergoing thoracoscopic surgery with single lung ventilation (OLV) for lung cystadenomas.
Methods
A total of 66 infants undergoing thoracoscopic surgery with OLV for lung cystadenomas in our hospital from February, 2018 to February, 2019 were randomized into conventional ventilation groups (group N, n=33) and inverse ventilation group (group R, n=33). Hemodynamics and respiratory parameters of the infants were recorded and arterial blood gas analysis was performed at 15 min after two lung ventilation (TLV) (T1), OLV30 min (T2), OLV60 min (T3), and 15 min after recovery of TLV (T4). Bronchoalveolar lavage fluid was collected before and after surgery to detect the expression level of advanced glycation end product receptor (RAGE).
Results
Sixty-three infants were finally included in this study. At T2 and T3, Cdyn, PaO2 and OI in group R were significantly higher (P < 0.05) and Ppeak, PaCO2 and PA-aO2 were significantly lower than those in group N (P < 0.05). There was no significant difference in HR or MAP between the two groups at T2 and T3 (P > 0.05). The level of RAGE significantly increased after the surgery in both groups (P < 0.05), and was significantly lower in R group than in N group (P < 0.05).
Conclusion
In infants undergoing thoracoscopic surgery with OLV for pulmonary cystadenoma, appropriate IRV combined with PEEP does not affect hemodynamic stability and can increases pulmonary compliance, reduce the peak pressure, and improve oxygenation to provide pulmonary protection.
Keywords: inverse ratio ventilation, positive end-expiratory pressure, one lung ventilation, infants, Pulmonary cystadenoma
胸腔镜已被应用于小儿胸科手术，其中单肺通气技术（OLV）被认为是小儿胸腔镜手术的一大重点难点[1-2]（图 1），由于小儿特殊的生理特点，OLV时较成人更易引起低氧血症及肺损伤[3-4]。有研究显示[5-7]，在急性呼吸窘迫综合征的治疗中，反比通气（IRV）和呼气末正压（PEEP）均可一定程度上改善呼吸动力学和氧代谢指标。目前国内外探讨婴儿OLV时氧合和肺保护的相关研究很少，虽然国内曾有一些IRV应用于OLV成人的研究[8]，但IRV联合PEEP对OLV婴儿的影响尚未见报道。鉴于保护性通气策略在儿童机械通气应用中的重要作用[9-10]，本研究将IRV联合PEEP应用于肺囊腺瘤术OLV婴儿（图 2），其综合效果及安全性是怎样呢？现将结果报道如下。
1.
胸腔镜下婴儿单肺通气
One lung ventilation for thoracoscopic infants.
2.
反比通气联合PEEP应用于胸腔镜婴儿肺囊腺瘤术
Inverse ratio ventilation combined with PEEP for thoracoscopic pulmonary cystadenomas in infants.
1. 资料和方法
1.1. 一般资料
选择2018年2月~2019年2月于广东省妇幼保健院择期行胸腔镜下肺囊腺瘤手术OLV的患儿，性别不限，年龄42~358 d，体质量4.1~14.5 kg。入选标准：ASAI~Ⅱ级，术前各项检查无明显异常，OLV时间 > 1 h。排除标准：术前发热体温≥38 ℃或肺部感染呼吸功能不全；有严重循环系统疾病；OLV时脉搏血氧饱和度（SPO2）经处理无法维持在90%以上，术中出现难以维持气道峰压低于30 cmH2O；术中出血量超过血容量20%；术中因手术需要转开胸手术患儿；OLV时间 < 1 h或手术时间超过3 h。本研究经广东省妇幼保健院医学伦理协会批准，并与患儿家属签署知情同意书。按随机数字表法将患儿分为常规通气组（N组，n=33）和反比通气组（R组，n=33）。最终63例患儿入选本研究。其中，R组1例术中中转开胸，N组1例Ppeak无法维持低于30 cmH2O，N组1例OLV时间小于1 h。两组基线资料有可比性。
1.2. 麻醉方法
入室后常规监测一般生命体征，建立静脉通路。静脉注射咪唑安定0.1~0.2 mg/kg，丙泊酚2~4 mg/kg，舒芬太尼0.3~0.5 μg/kg，顺阿曲库铵0.1~0.2 mg/kg行全麻诱导。充分给氧去氮后，根据胸部CT测量健侧主支气管直径选择导管型号（单腔气管导管3.0~4.0），两组均插入单腔气管导管于主气管，接Drager型麻醉机。B超引导下颈内静脉、桡动脉穿刺置管同时连续监测SpO2、心电图、血压、体温、出血量及尿量。采用宾得EB-270P型直径为2.4 mm电子纤维支气管镜辅助将单腔气管导管插入健侧主支气管。麻醉维持用3%七氟醚吸入，根据麻醉深度间断给予舒芬太尼0.3 μg/kg，顺阿曲库铵0.1 mg/kg。根据手术需要调节麻醉深度，用BIS监测仪使麻醉深度维持在BIS值40~55，用TOF监测肌松。用变温水毯等保温措施维持患儿体温正常。手术结束后退气管导管至主气管行双肺通气，吸痰。术后转入麻醉恢复室，待患儿意识恢复，TOF > 90%时拔出气管导管。
1.3. 通气策略
所有患儿均采用压力控制模式通气模式。双肺通气（TLV）时，气道压力：12~18 cmH2O，呼吸频率（RR）：23~30次/min，潮气量（TV）：8~10 mL/kg，吸呼比（:I E）：1:1.5，PEEP：0 cmH2O，吸入氧浓度（FiO2）：100%，氧流量：1.5 L/min。OLV后调整气道压力：12~30 cmH2O，RR：25~45次/min，TV：5~7 mL/kg，FiO2：50%~100%，PEEP：5 cmH2O，R组为I:E：1.5:1，N组为I:E：1:1.5，除I:E不同外，呼吸机其他参数两组保持一致。术中调节吸氧浓度、呼吸频率和气道压力，使得维持呼气末二氧化碳分压（PETCO2）35~80 mmHg和SPO2 > 90%。
1.4. 观察指标
在TLV15 min（T1）、OLV30 min（T2）、OLV60 min（T3）、恢复TLV15 min（T4）四个时间点，分别记录患儿血流动力学和呼吸参数，包括心率（HR）、平均动脉压（MAP）、Ppeak等。采集动脉血进血行气分析，包括动脉二氧化碳分压（PaCO2）、动脉血氧分压（PaO2）等。于术前（支气管插管后）和术后（气管导管退至主气管前）行支气管灌洗，灌洗使用1 mL/kg温生理盐水，支气管灌洗液（BALF）通过负压回收至一次性无菌硅化收集器收集，要求回收率 > 30%。采用ELISA试剂盒（R & D Systems）检测BALF中晚期糖基化终末产物受体（RAGE）的表达水平。利用公式计算动态肺顺应性（Cdyx）、氧合指数（OI）和肺泡动脉氧分压差（PA-aO2）。Cdyx=Vt/（Ppeak-PEEP），OI=PaO2/FiO2，PA-aO2=[（PBPH2O）FiO2-PACO2/R]-PaO2。
1.5. 统计分析
采用SPSS 20.0软件进行统计分析。符合正态分布的计量资料以均数±标准差表示，组间均数比较采用t检验，重复测量资料比较采用重复测量方差分析。计数资料以例数（率）表示，组间比较采用卡方检验，P < 0.05为差异有统计学意义。
2. 结果
2.1. 一般情况和并发症
两组患者性别、年龄、体质量、OLV时间、手术时间及拔管时间差异均无统计学意义（P > 0.05）；术后低氧血症N组1例（3.2%），R组1例（3.1%），两组差异无统计学意义（P > 0.05）。两组均未见苏醒延迟、肺不张和气胸等并发症（表 1）。
1.
两组一般情况和并发症比较
General data and complications in the two groups (Mean±SD, n=63)
| Group | Gender(M/F) | Age(day) | Weight(kg) | OLV time(min) | Operative time (min) | Extubation time (min) | Postoperative complications (cas) |
| R (n=32) | 18/14 | 195.6±58.2 | 7.8±1.6 | 71.5±8.7 | 111.3± 22.4 | 35.2±7.4 | 1 |
| N (n=31) | 17/14 | 211.5±70.5 | 8.3±1.5 | 75.2±13.1 | 120.6± 18.2 | 33.2±6.3 | 1 |
2.2. 血流动力学参数和呼吸参数
与T1时比较，两组在T2、T3时间点的HR、Ppeak均增高，MAP、Cdyn下降（P < 0.05）；R组在T2、T3时间点的Cdyn显著高于N组同时间点，Ppeak显著低于N组同时间点（P < 0.05），T2、T3时间点的HR和MAP两组间比较差异无统计学意义（P > 0.05，表 2）。
2.
两组不同时点血流动力学参数和呼吸参数比较
Hemodynamic and respiratory parameters at different time points in the two groups (Mean±SD, n=63)
| Group | HR (bpm) | MAP (mmHg) | Ppeak (cmH2O) | Cdyx (mL/cmH2O) |
| #P < 0.05 vs the group N, △P < 0.05 vs T1 of the same group. | ||||
| R (n=32) | ||||
| T1 | 124.5±13.2 | 72.4±9.1 | 14.4±3.3 | 13.1±3.6 |
| T2 | 145.4±16.3△ | 59.5±8.8△ | 21.5±2.6#△ | 10.2±1.3#△ |
| T3 | 142.7±17.3△ | 63.4±7.9△ | 21.1±3.3#△ | 9.7±0.9#△ |
| T4 | 130.3±15.3 | 70.2±8.4 | 17.1±3.2 | 11.7±2.6 |
| N (n=31) | ||||
| T1 | 127.3±14.7 | 74.3±9.3 | 16.6±5.1 | 13.3±3.1 |
| T2 | 143.8±18.6△ | 60.6±8.5△ | 24.8±1.4△ | 8.7±0.9△ |
| T3 | 140.7±17.2△ | 64.2±8.1△ | 24.9±1.9△ | 8.1±0.7△ |
| T4 | 129.2±13.2 | 69.8±9.2 | 18.1±4.6 | 10.7±1.7 |
2.3. 血气分析
与T1时比较，两组T2、T3时点PaO2、OI均降低，PaCO2、PA-aO2均增高，差异有统计学意义（P < 0.05）；在T2、T3时点，R组PaO2、OI显著高于N组同时间点，差异有统计学意义（P < 0.05），PaCO2、PA-aO2显著低于N组同时间点，差异有统计学意义（P < 0.05，表 3）。
3.
两组不同时点动脉血气分析指标比较
Arterial blood gas analysis at different time points in the two groups (Mean±SD, n=63)
| Group | PaCO2 (mmHg) | PaO2 (mmHg) | OI (mmHg) | PA-aO2 (mmHg) |
| #P < 0.05 vs group N, △P < 0.05 vs T1 of the same group. | ||||
| R (n=32) | ||||
| T1 | 35.5±3.9 | 394.4±25.2 | 581.±72.5 | 137.3±22.4 |
| T2 | 39.6±3.2#△ | 125.4±23.8#△ | 168.1±52.0#△ | 272.7±46.4#△ |
| T3 | 45.1±3.8#△ | 152.1±52.5#△ | 171.3±53.9#△ | 301.4±50.9#△ |
| T4 | 36.8±4.9 | 245.1±55.2 | 318.7±61.9 | 263.3±67.9 |
| N (n=31) | ||||
| T1 | 36.8±3.7 | 407.7±37.4 | 572.0±74.8 | 132.0±21.8 |
| T2 | 56.0±4.9△ | 100.6±24.5△ | 111.2±49.8△ | 353.3±51.7△ |
| T3 | 63.3±4.2△ | 103.0±28.4△ | 114.6±50.5△ | 364.7±59.6△ |
| T4 | 39.2±7.9 | 282.3±64.2 | 325.5±63.8 | 247.0±64.5 |
2.4. RAGE表达水平
与同组术前相比，两组术后RAGE都明显增高，差异有统计学意义（P < 0.05）；两组患儿术前RAGE表达水平组间比较并无统计学差异（P > 0.05），而在术后R组与N组相比RAGE表达水平较低，差异有统计学意义（P < 0.05，表 4）。
4.
两组术前术后RAGE表达水平比较
Comparison of RAGE expression levels before and after surgery in the two groups (Mean±SD, n=63)
| Group | Preoperative time | Postoperative time |
| #P < 0.05 vs group N, △P < 0.05 vs the preoperative time of the same group. | ||
| R (n=32) | 2173.2±511.4 | 3546.3±647.2#△ |
| N (n=31) | 2245.4±505.2 | 4337.7±923.8△ |
3. 讨论
近年来随着对OLV肺损伤机制的不断认识和临床实践，有研究提出通过综合运用肺保护性通气策略来减少OLV带来的肺损伤，并在临床应用中取得一定效果[11-12]，本研究实施IRV联合PEEP的肺保护性通气策略，试探讨其在OLV肺囊腺瘤婴儿中的应用效果。有研究指出[13]，I:E=1:1时胸腔镜术中OLV动脉氧分压无明显改善，且考虑小儿相比成人需要足够的吸气时间，本研究根据预实验结果采用I:E=1.5:1的小儿IRV。合适的PEEP可以使肺泡复张，减少通气血流比失调，但过高或过低水平的PEEP不但不利于肺通气还可能造成相关肺损伤，鉴于已有研究经验[14-15]，本实验选取低水平PEEP=5 cmH2O。考虑压力模式控制气道压更有利于减少患者血流动力学的波动，更适用于应用OLV的胸科手术患者，故本研究采用压力通气模式[16-17]。基于婴儿单肺通气肺保护的需要和保护性通气策略前期临床研究[18-19]，本研究采用允许性高碳酸血症，在术中维持PETCO2 35~80 mmHg。
不合适的IRV和PEEP，都有可能引起气压伤，呼吸顺应性呈逐渐下降趋势，心排血量减少，对循环的抑制加重[13, 20-21]。而本研究结果显示，R组在T2、T3的Ppeak明显低于N组，且Cdyn高于N组，这可能是由于IRV通过延长吸气时间使肺膨胀时间延长，潮气量以较低的速度进入肺，使得其峰压Ppeak较低[22]，而呼气时间相对缩短，使肺功能残气量增加，部分萎陷的肺泡复张，提高了Cdyn[23]。同时低水平PEEP进一步使肺泡复张，减少通气血流比失调，协同提高了Cdyn。本研究血流动力学结果显示，T2、T3时间点的HR和MAP两组间比较差异无统计学意义（P > 0.05），考虑是低水平PEEP和IRV皆能复张基底部的肺泡，使低通气区肺血管的收缩反应减慢，适当减少了右心室的后负荷，并不影响血流动力学稳定，与已有研究一致[14]。
本研究结果显示，R组在T2、T3时PA-aO2低于同时间点N组（P < 0.05），考虑IRV和PEEP使部分萎陷的肺泡复张，增加弥散面积，进而促进肺换气功能加强。同时，本研究显示R组在T2、T3时PaO2、OI显著高于N组同时间点（P < 0.05），分析其原因可能是动脉氧合状态是一个复杂的生理过程，受多个因素影响，如肺通气的程度、局部肺通气流量、肺换气、心脏功能等。IRV使萎陷的肺泡开放，影响部分区域通气/血流灌注比例，改善肺弥散功能，同时通气得到改善，进而提高氧合指数，有研究显示出与本结果的一致性[5, 24]。
随着儿童机械通气的发展，越来越多的研究开始关注呼吸机相关性肺损伤指标的监测，为此本实验进一步检测了两组患儿术前术后肺泡灌洗液中RAGE的水平。RAGE主要表达于Ⅰ型肺泡上皮细胞中，并与Ⅱ型肺泡上皮细胞转分化相关，它的释放与肺部急性损伤高度相关[25-27]。本研究结果显示，两组术后RAGE水平较术前均明显增高，而R组术后RAGE水平较N组要低，说明IRV联合PEEP可在某程度上减轻肺部相关损伤。考虑除了归因于IRV降低峰压致气压伤减少的肺保护作用外，还可能与IRV和PEEP都能复张部分萎陷的肺泡，从而减轻肺不张性机械通气相关肺损伤有关，同时，肺部炎症介质释放是引起损伤性机械通气重要因素，有报道显示[22, 28]IRV能减轻机械通气对肺泡的刺激，减少炎性因子释放，与本研究结果一致。
两组患者在术后并发症上无统计学差异，考虑本实验在严格实施排出标准时已经将可能出现术后并发症的患儿剔除，以及手术OLV时间不长和实验样本量有限等原因造成。因而，IRV联合PEEP在临床上的优势特点还有待大样本、多中心研究证实。
综上所述，合适的IRV联合PEEP应用于胸腔镜下肺囊腺瘤术的OLV婴儿患者，既不影响血流动力学稳定，同时能增加肺顺应性，降低峰压，改善氧合，安全可行，有一定的肺保护作用。
Biography
王昀，硕士，主治医师，E-mail: foreverwangyun@163.com
Funding Statement
广东省科技计划项目（2017ZC0318）；广东省医学科学技术研究基金（A2016173）
Contributor Information
王 昀 (Yun WANG), Email: foreverwangyun@163.com.
黎 昆伟 (Kunwei LI), Email: likunwei1979@163.com.
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