气道湿化对机械通气所致肺损伤的影响

Effect of airway humidification on lung injury induced by mechanical ventilation

目的 探讨气道湿化对不同潮气量（VT）机械通气所致肺损伤的影响。方法 将24只雄性日本大耳白兔按随机数字表法分为小VT组、大VT组、小VT湿化组、大VT湿化组4组，每组6只。所有动物均在气管切开插管后行机械通气6 h，小VT为8 mL/kg、大VT为16 mL/kg，吸入氧浓度（FiO2）为0.40，呼气末正压（PEEP）为0；湿化组通过加热型湿化器维持呼吸回路Y件处的温度在40℃左右。通气0、2、4、6 h行动脉血气分析〔pH值、动脉血氧分压（PaO2）和动脉血二氧化碳分压（PaCO2）〕和肺机械力学〔气道峰压（Ppeak）、气道阻力（Raw）、肺顺应性〕监测；采用酶联免疫吸附试验（ELISA）测定血浆及支气管肺泡灌洗液（BALF）中肿瘤坏死因子-α（TNF-α）和白细胞介素-8（IL-8）水平。机械通气后处死动物，计算肺组织湿/干质量（W/D）比值；光镜下观察肺组织病理学改变并进行评分，扫描电镜和透射电镜下观察气道纤毛及气道上皮改变。结果 与小VT组比较，大VT组pH值明显升高，PaCO2明显降低，PaO2无明显变化，通气过程中Ppeak、Raw、肺顺应性均明显升高。小VT湿化组血气分析指标、肺机械力学指标与小VT组比较均无差异。与大VT组比较，大VT湿化组PaCO2明显降低，Ppeak明显升高，pH值、PaO2、Raw、肺顺应性均无明显差异。与小VT湿化组比较，大VT湿化组血气分析指标无明显差异，Ppeak、Raw、肺顺应性明显升高〔PaCO2（mmHg，1 mmHg＝0.133 kPa）2 h：27.96±4.64比36.08±2.11，4 h：28.62±2.93比34.55±5.50，6 h：29.33±2.14比35.01±5.53；Ppeak （cmH2O，1 cmH2O＝0.098 kPa）0 h：14.34±1.97比8.84±1.32，2 h：17.33±0.52比11.17±2.14，4 h：17.83±0.98比12.67±2.06，6 h：18.67±1.22比13.50±2.16；Raw（cmH2O）0 h：37.36±5.14比27.05±2.93，2 h：43.94±6.58比31.95±3.56，4 h：48.04±6.07比35.24±3.50，6 h：50.33±6.34比36.66±3.64；肺顺应性（mL/cmH2O）6 h：2.28±0.18比1.86±0.37，均P＜0.05〕。大VT组肺W/D比值较小VT组明显升高（6.17±2.14比3.50±1.52，P＜0.05）；而大VT湿化组肺W/D比值高于小VT湿化组，但差异无统计学意义（5.17±2.14比3.00±1.10，P＞0.05）。镜下观察显示：小VT组气道纤毛部分脱落，有倒伏、粘连，轻度稀疏；大VT组纤毛严重脱落，尚存的纤毛稀疏并且倒伏，细胞结构破坏，肺组织病理损伤评分较小VT组明显升高（分：6.17±2.14比3.50±1.52，P＜0.05）；小VT湿化组纤毛正常，细胞结构清晰，肺组织病理损伤评分与小VT组比较无差异（分：3.00±1.10比3.50±1.52，P＞0.05）；大VT湿化组纤毛明显稀疏，严重粘连、倒伏，细胞结构不清晰，肺组织病理损伤评分高于小VT湿化组，但差异无统计学意义（5.17±2.14比3.00±1.10，P＞0.05）。通气过程中各组血浆和BALF中炎症介质TNF-α、IL-8浓度未见明显变化，各组间也并未出现统计学差异。结论 气道湿化降低了小VT及大VT机械通气所致的肺组织病理损害、气道纤毛损伤和气道细胞结构损害。大VT湿化时会出现明显的肺水肿。

Objective To explore the effect of airway humidification on lung injury as a result of mechanical ventilation with different tidal volume（VT）. Methods Twenty-four male Japanese white rabbits were randomly divided into four groups：low VT with airway humidification group,high VT with airway humidification group,low VT and high VT group without humidification,with 6 rabbits in each group. Mechanical ventilation was started after intubation and lasted for 6 hours. Low VT denoted 8 mL/kg,while high VT was 16 mL/kg,fraction of inspired oxygen （FiO2）denoted 0.40,positive end-expiratory pressure（PEEP）was 0. Temperature at Y piece of circuit in airway humidification groups was monitored and controlled at 40℃. Arterial blood gas analysis,including pH value,arterial partial pressure of oxygen（PaO2）,arterial partial pressure of carbon dioxide（PaCO2）,lung mechanics indexes, including peak airway pressure（Ppeak）and airway resistance（Raw）,and lung compliance was measured at 0,2,4, 6 hours of mechanical ventilation. The levels of tumor necrosis factor-α（TNF-α）and interleukin-8（IL-8）in plasma and bronchoalveolar lavage fluid（BALF）were determined by enzyme linked immunosorbent assay（ELISA）. The animals were sacrificed at the end of mechanical ventilation. The wet to dry（W/D）ratio of lung tissues was calculated. Histopathologic changes in the lung tissueies were observed with microscope,and lung injury score was calculated. Scanning and transmission electron microscopies were used to examine the integrity of the airway cilia and the tracheal epithelium. Results Compared with low VT group,pH value in high VT group was significantly increased,PaCO2 was significantly lowered,and no difference in PaO2 was found. Ppeak,Raw,and lung compliance were significantly increased during mechanical ventilation. There were no significant differences in blood gas analysis and lung mechanics indexes between low VT with airway humidification group and low VT group. Compared with high VT group,PaCO2 in high VT with airway humidification group was significantly decreased,Ppeak raised obviously,and no difference in pH value,PaO2,Raw and pulmonary compliance was found. Compared with low VT with airway humidification group,no difference in blood gas analysis（PaCO2,mmHg,1 mmHg=0.133 kPa）was found,but Ppeak（cmH2O,1 cmH2O=0.098 kPa）,Raw（cmH2O）,and lung compliance（mL/cmH2O）were increased significantly in high VT with airway humidification group（PaCO2 at 2 hours：27.96±4.64 vs. 36.08±2.11,4 hours：28.62±2.93 vs. 34.55±5.50, 6 hours：29.33±2.14 vs. 35.01±5.53;Ppeak at 0 hour：14.34±1.97 vs. 8.84±1.32,2 hours：17.33±0.52 vs. 11.17±2.14,4 hours：17.83±0.98 vs. 12.67±2.06,6 hours：18.67±1.22 vs. 13.50±2.16;Raw at 0 hour：37.36±5.14 vs. 27.05±2.93,2 hours：43.94±6.58 vs. 31.95±3.56,4 hours：48.04±6.07 vs. 35.24±3.50, 6 hours：50.33±6.34 vs. 36.66±3.64;pulmonary compliance at 6 hours：2.28±0.18 vs. 1.86±0.37,all P〈0.05）. The lung W/D ratio in high VT group was significantly higher than that of the low VT group（6.17±2.14 vs. 3.50±1.52, P〈0.05）. W/D in high VT with airway humidification group was higher than that of low VT with airway humidification group but without statistically significant difference（5.17±2.14 vs. 3.00±1.10,P〉0.05）. Microscopic observation showed that cilia were partially detached,adhered and sparse in low VT group,while cilia in high VT group showed serious detachment and lodging. Remaining cilia were sparse,with lodging,and cellular structure was damaged. Lung tissue pathological injury score in the high VT group was significantly higher than that of low VT group（6.17±2.14 vs. 3.50±1.52,P〈0.05）. Cilia density and cellularity were normal in low VT with airway humidification group,and no difference in lung tissue pathological injury score was found compared with low VT group（3.00±1.10 vs. 3.50±1.52, P〉0.05）. Cilia were severely detached,adhered and lodging,and cellularity were not obvious in high VT with airway humidification group,and lung tissue pathological injury score was elevated significantly than that of the low VT with airway humidification group but without statistically significant difference（5.17±2.14 vs. 3.00±1.10,P〉0.05）. TNF-α and IL-8 concentrations showed no change in plasma and BALF in all groups during ventilation,and no significant difference was found among the groups. Conclusions Airway humidification can alleviate pathological lung injury,damage of cilia and cellular structure in trachea caused by mechanical ventilation with low and high VT. High VT with humidification can result in serious pulmonary edema.