Intermittent alveolar overdistension for 30 or 240 minutes does not produce acute lung injury in normal pig lung

BACKGROUND: The objective is to study whether alveolar overdistension can induce acute lung injury in pigs as assessed by analysis of respiratory and histological parameters and inflammatory markers. MATERIALS AND METHODS: Experimental study, using mixed-breed pigs. Animals were assigned to one of the following groups: Control Group (CG) (n = 5), applying mechanical ventilation with tidal volume (Vt) of 10 ml/kg, respiratory rate (RR) of 18 bpm, and FiO2 of 1 for 240 min; High Vt for 30 min (HVt-30) Group (n = 5), applying ventilation with Vt of 50 ml/kg and RR of 8 bpm and FiO2 of 1 for 30 min, followed by ventilation as in the CG for a further 210 min; and HVt-240 Group (n = 5), applying ventilation with Vt of 50 ml/kg, RR of 8 bpm, and FiO2 of 1 for 240 min. Hemodynamic parameters, airway pressures, arterial blood gases, extravascular lung water (EVLW), and cytokines (IL-2, IL-4, IL-6, IL-10, TNF-alpha, and ITF-gamma) in plasma and bronchoalveolar lavage (BAL) were determined. Lungs were fixed with 10% formalin for histological analysis. Results are expressed as mean +/- standard deviation. The ANOVA test was used to compare measurements among the three groups. RESULTS: At 30 min, airway pressures and oxygenation of HVt-30 and HVt-240 groups were higher than those of controls [Pplateau: 39.2 +/- 5.6 and 33.0+/- 5.1 versus 12.2 +/- 1.3 (P < 0.01); PaO2/FiO2: 443.8 +/- 55 and 430.6 +/- 34 versus 194.4 +/- 77 (P < 0.01)]. In HVt-240 group, these parameters were also higher than in the other two groups at the subsequent measurement times. There were no differences among the groups in EVLW values. Cytokines were undetected or negligible in plasma and BAL in all of the groups. The histological analysis showed no changes suggestive of acute lung injury. CONCLUSIONS: In this animal model, ventilation for 4 h with large tidal volume did not cause ventilator-induced lung injury.     

Perioperative lung injury

Patients are at risk for several types of lung injury in the perioperative period. These injuries include atelectasis, pneumonia, pneumothorax, bronchopleural fistula, acute lung injury and acute respiratory distress syndrome. Anesthetic management can cause, exacerbate or ameliorate most of these injuries. Clinical research trends show that traditional protocols for perioperative mechanical ventilation, using large tidal volumes without positive end-expiratory pressure (PEEP) can cause a sub-clinical lung injury and this injury becomes clinically important when any additional lung injury is added. Lung-protective ventilation strategies using more physiologic tidal volumes and appropriate levels of PEEP can decrease the extent of this injury.     

Effect of pulmonary artery pressure on extravascular lung water in an experimental model of acute lung injury

BACKGROUND: Lung edema can be influenced by hemodynamic changes in pulmonary circulation. The aim of this study was to evaluate, in an experimental model of acute lung injury, the effect on extravascular lung water (EVLW) of an increase in pulmonary artery pressure (Ppa) without changes in cardiac output and wedge pressure. METHODS: Lung edema was produced by an intravenous oleic acid infusion in mixed-breed pigs weighing 25-31 kg, which, after 20 min, were randomly assigned to a control group (100% FiO(2)) (n = 6) or a high Ppa group (21% FiO(2)) (n = 7). An increase in pulmonary artery pressure of at least 40% over baseline was produced in the high Ppa group by alveolar hypoxia. Hemodynamic, ventilatory and gas exchange parameters were collected at regular intervals. Pulmonary, wedge and capillary pressures were measured with a pulmonary artery catheter and the occlusion technique. EVLW was calculated gravimetrically. RESULTS: At 240 min, both gravimetric-measured EVLW and mean pulmonary artery pressures were significantly higher (P < 0.05) in high Ppa animals vs. controls (12.06 +/- 4.21 vs. 7.98 +/- 2.46 ml/kg and 39.0 +/- 1.3 vs. 26.6 +/- 4.7 mmHg, respectively). Cardiac output (6.8 +/- 2.5 vs. 7.3 +/- 1.3) and pulmonary wedge pressures (9.2 +/- 1.7 vs. 9.4 +/- 2.8 mmHg) were similar. A difference was detected in pulmonary capillary pressures [17.0 +/- 3.3 (high Ppa) vs. 13.8 +/- 2.7 mmHg (controls)] but did not reach statistical significance. CONCLUSIONS: In this model, an increase in pulmonary artery pressure by alveolar hypoxia produces an increase in extravascular lung water, probably related to changes in pulmonary capillary pressures.     

机械通气肺损伤的基本机制

机械通气肺损伤发生机制复杂,临床表现多样,日益受到重视.其基本机制为对肺组织过度牵拉的机械因素和机械力学诱导的肺脏局部细胞因子和炎症介质的释放.不适当的机械通气除可造成气压损伤、容积损伤和肺不张损伤等机械性损伤外,其最后的共同途径可能是激活细胞内信号转导通路和加重炎症介质介导的肺局部炎症反应,即机械伤转化为生物伤.现就其发生机制、防治对策等方面的研究作一简要综述.     

Early treatment with arteriovenous extracorporeal lung assist and high-frequency oscillatory ventilation in a case of severe acute respiratory distress syndrome

BACKGROUND: Lung protective ventilation can reduce mortality in acute respiratory distress syndrome (ARDS). However, many patients with severe ARDS remain hypoxemic and more aggressive ventilation is necessary to maintain sufficient gas exchange. Pumpless arteriovenous extracorporeal lung assist (av-ECLA) has been shown to remove up to 95% of the systemic CO(2) production, thereby allowing ventilator settings and modes prioritizing oxygenation and lung protection. High-frequency oscillatory ventilation (HFOV) is an alternative form of ventilation that may improve oxygenation while limiting the risk of further lung injury by using extremely small tidal volumes (VT). METHODS: We discuss the management of a patient suffering from severe ARDS as a result of severe bilateral lung contusions and pulmonary aspiration. RESULTS: Severe ARDS developed within 4 h after intensive care unit admission. Conventional mechanical ventilation (CV) with high-airway pressures and low VT failed to improve gas exchange. Av-ECLA was initiated to achieve a less aggressive ventilation strategy. VT was reduced to 2-3 ml/kg, but oxygenation did not improve and airway pressures remained high. HFOV (8-10 Hz) was started using a recruitment strategy and oxygenation improved within 2 h. After 5 days, the patient was switched back to CV uneventfully and av-ECLA was removed after 8 days. CONCLUSION: The combination of two innovative treatment modalities resulted in rapid stabilization and improvement of gas exchange during severe ARDS refractory to conventional lung protective ventilation. During av-ECLA, extremely high oscillatory frequencies were used minimizing the risk of baro- and volutrauma.     

Extracellular thioredoxin levels are increased in patients with acute lung injury

BACKGROUND: Acute lung injury (ALI) and its extreme manifestation the acute respiratory distress syndrome (ARDS) complicate a wide variety of serious medical and surgical conditions. Thioredoxin is a small ubiquitous thiol protein with redox/inflammation modulatory properties relevant to the pathogenesis of ALI. We therefore investigated whether thioredoxin is raised extracellulary in patients with ALI and whether the extent of any increase is dependent upon the nature of the precipitating insult. METHODS: Bronchoalveolar lavage (BAL) fluid and plasma samples were collected from patients with ALI (n=30) and healthy controls (n=18, plasma; n=14, BAL fluid). Lung tissue was harvested from a separate group of patients and controls (n=10). Thioredoxin was measured by ELISA in fluids and by immunohistochemistry in tissue. Interleukin (IL)-8 levels were determined by ELISA. Disease severity was assessed as APACHE II and SOFA scores. RESULTS: BAL fluid levels of thioredoxin were higher in patients with ALI than in controls (median 61.6 ng/ml (IQR 34.9-132.9) v 16.0 ng/ml (IQR 8.9-25.1), p<0.0001); plasma levels were also significantly higher. When compared with controls, sections of wax embedded lung tissue from patients with ALI showed greater positive staining for thioredoxin in alveolar macrophages and type II epithelial cells. BAL fluid levels of thioredoxin correlated with IL-8 levels in BAL fluid but not with severity of illness scores or mortality. BAL fluid levels of thioredoxin, IL-8, and neutrophils were significantly greater in patients with ALI of pulmonary origin. CONCLUSIONS: Extracellular thioredoxin levels are raised in patients with ALI, particularly of pulmonary origin, and have a significant positive association with IL-8. Extracellular thioredoxin levels could provide a useful indication of inflammation in ALI.     

右美托咪定对ARDS机械通气患者炎症因子及肺损伤的影响

目的观察右美托咪定对急性呼吸窘迫综合症(ARDS)机械通气患者炎症因子及肺损伤的影响。方法选择40例ARDS机械通气患者,根据患者使用和未使用右美托咪定,将患者分成右美托咪定组(右美托咪定组,n=20)和对照组(n=20)。前者静脉泵注右美托咪定负荷量1μg/kg 15 min,再以0.2~0.7μg/kg·h速率持续输注48 h;对照组患者静脉泵注丙泊酚3~5 mg/(kg·h)为48 h,两组均复合舒芬太尼0.1~0.2μg/(kg·h)。分别于插管前(T0)、插管后6 h(T1)、12 h(T2)、24 h(T3)、48 h(T4)各时间点抽取静脉血检测IL-6、IL-8、IL-10的浓度,同时记录Pa O2/Fi O2。结果与T0时比较,T1~T4时两组的IL-6、IL-8、IL-10的浓度显著升高(P0.05),D组Pa O2/Fi O2T2~T4时显著增高(P0.05)、C组T1~T4时显著降低(P0.05),HR在T1~T4时D组降低,C组增高(P0.05)。与C组比较,T2~T4时D组IL-6、IL-8显著降低、IL-10显著升高(P0.05);T2~T4时Pa O2/Fi O2升高(P0.05);T1~T4时D组HR降低,T2~T4时MAP升高(P0.05)。结论右美托咪定用于ARDS机械通气治疗患者,可以平衡炎症因子的释放,有利于减轻肺损伤。     

Azithromycin reduces airway inflammation in a murine model of lung ischaemia reperfusion injury.

Clinical studies revealed that azithromycin reduces airway neutrophilia during chronic rejection after lung transplantation. Our aim was to investigate the possible effect of azithromycin on ischaemia-reperfusion injury. Azithromycin or water was administered to mice every other day during 2 weeks (n = 6/group). On the 14th day, the left lung was clamped to induce ischaemia (90 min). In two additional groups, animals underwent the same protocol, followed by 4 h of reperfusion. Two control groups were included with thoracotomy only. Inflammatory parameters and oxidative stress were measured in broncho-alveolar lavage of the left lung. Leukocytes, lymphocytes, neutrophils, 8-isoprostane and IL-1beta levels after ischaemia and reperfusion were significantly reduced in mice treated with azithromycin. There was a trend towards lower IL-6 and KC levels. A significant correlation was seen between 8-isoprostanes and neutrophils (Pearson r = 0.72; P = 0.0086), IL-6 (Pearson r = 0.84; P = 0.0006), KC (Pearson r = 0.88; P = 0.0002) and IL-1beta (Pearson r = 0.62; P = 0.0326). We conclude (i) that azithromycin reduces inflammation and oxidative stress in our IRI model, and (ii) that oxidative stress is correlated with the number of neutrophils and IL-6, KC and IL-1beta levels after ischaemia and reperfusion. Azithromycin should be further investigated as a novel drug to prevent lung ischaemia-reperfusion injury.     

肺保护性通气对肝移植手术患者肺损伤血清生物标志物和炎性因子的影响

目的观察肺保护性通气对肝移植手术患者肺损伤血清生物标志物和炎性因子的影响,探讨其对肝移植术后急性肺损伤(acute lung injury,ALI)的影响。方法选择行原位肝移植术的终末期肝病患者60例,男42例,女18例,年龄21~62岁,体重43~80kg,ASAⅡ~Ⅳ级。随机分为肺保护性通气组(P组)和非肺保护性通气组(U组),每组30例。所有患者分别于麻醉后手术开始前(T_1)、机械通气3h(T_2)、新肝期2h(T_3)及新肝期4h(T_4)检测肺动脉血中肺损伤血清生物标志物和炎性因子的水平,包括克拉拉细胞分泌蛋白16(CC16)、表面活性蛋白(SP-D)及高级糖基化终末产物可溶性受体(sRAGE)、TNF-α、IL-6及IL-8;于T_1~T_4、术后2h(T_5)、拔管前(T_6)及术后2d(T_7)行桡动脉血血气分析。记录患者术后清醒时间、拔管时间、ICU停留时间及ALI的发生情况。结果与T_1时比较,T_2~T_4时两组血清CC16浓度明显升高(P0.05或P0.01);T_3时两组SPD、sRAGE、TNF-α、IL-6及IL-8浓度明显升高(P0.01);T_4时sRAGE、TNF-α、IL-6和IL-8浓度明显升高(P0.05或P0.01);T_2、T_5、T_6时两组氧合指数(OI)明显升高(P0.05或P0.01),T_4时P组明显降低(P0.01),T_3、T_4时U组明显降低(P0.01)。T_2、T_3时P组CC16浓度明显低于U组(P0.05或P0.01);T_3时P组OI明显高于U组(P0.05);P组术后拔管时间明显短于U组[(8.9±3.2)h vs(9.3±2.8)h,P0.05]。P组术后ALI 5例(16.6%),U组术后ALI 7例(23.3%),两组差异无统计学意义。结论肺保护性通气可改善肝移植手术患者的氧合指数,缩短拔管时间,减轻肺损伤。     

Evaluation of lung and chest wall mechanics during anaesthesia using the PEEP-step method

Background

Postoperative pulmonary complications are common. Between patients there are differences in lung and chest wall mechanics. Individualised mechanical ventilation based on measurement of transpulmonary pressures would be a step forward. A previously described method evaluates lung and chest wall mechanics from a change of ΔPEEP and calculation of change in end-expiratory lung volume (ΔEELV). The aim of the present study was to validate this PEEP-step method (PSM) during general anaesthesia by comparing it with the conventional method using oesophageal pressure (PES) measurements.

肝移植术后急性肺损伤/急性呼吸窘迫综合征的研究进展

急性肺损伤/急性呼吸窘迫综合症（ALI/ARDS）是肝移植术后常见的并发症,可延长受者术后重症监护室入住时间,影响肝移植手术疗效,病情严重可致受者死亡,临床中引起了肝移植外科医师的高度重视。肝移植术后ALI/ARDS可由肺源性因素（例如机械通气相关肺损伤、肺部感染、误吸等）直接导致,也可由非肺源性因素（例如肺部以外的严重感染、输血、缺血-再灌注损伤等）间接导致。本文对肝移植术后ALI/ARDS的诊断标准及发生情况、发生机制、危险因素、实验室及临床诊断方法以及治疗方法等进行综述,加深对肝移植围手术期ALI/ARDS的理解与认知,以期为肝移植术后ALI/ARDS的诊治提供借鉴。     

右美托咪定对肺癌根治术患者单肺通气相关肺损伤的影响

目的 评价右美托咪定对肺癌根治术患者单肺通气(OLV)相关肺损伤的影响.方法 选择择期行肺癌根治手术的患者40例,男30例,女10例,年龄42～70岁,ASA Ⅰ或Ⅱ级,且术中OLV超过2 h.采用随机数字表法将患者分为两组:右美托咪定组(D组)和对照组(C组),每组20例.麻醉诱导后,D组给予右美托咪定初始剂量0.5...     

Comparison of conventional mandatory ventilation and high frequency oscillatory ventilation for treatment of acute lung injury induced by steam inhalation injury

This study compared pathophysical indexes, respiratory mechanics, circulatory parameters and lung injury scores of acute lung injury (ALI) induced by steam inhalation injury in a New Zealand rabbit model with different ventilatory strategies: a control group which consisted of lower tidal volume (VT 6 ml/kg) and high positive end-expiratory pressure (PEEP) (9 cmH₂O); treatment group which was high frequency oscillatory ventilation (HFOV). Eighteen rabbits were anaesthetized, sedated, neuromuscular-blocked and ventilated with above two modes at our animal laboratory of burn center. After induction of acute lung injury by steam inhalation, animals were randomizedly assigned to receive either conventional mechanical ventilation (CMV) or high frequency oscillatory ventilation and were grouped as CMV and HFOV group. As a result, HFOV attenuated the decrease in oxygenation and pulmonary compliance, alleviated lung tissue damage and inflammatory response. Therefore, HFOV may be a preferable option for treatment of acute lung injury induced by steam inhalation injury.     

反比通气联合PEEP对肺叶切除患者单肺通气时肺功能的影响

目的探讨反比通气联合PEEP对肺叶切除患者单肺通气时肺功能及炎症因子的影响。方法选择择期行肺叶切除术单肺通气的患者80例,男52例,女28例,年龄37~65岁,BMI21~29kg/m~2,ASAⅡ级,随机分为反比通气组与常规通气组,每组40例。支气管插管全麻后机械通气,反比通气组为I∶E 2∶1,VT7mL/kg,RR 12次/分,PEEP 5mH_2O;常规通气组为I∶E 1∶2,其他参数不变。记录麻醉前(T0)、麻醉后5min(T_1)、单肺通气开始(T_2)、单肺通气45 min(T_3)及手术结束(T4)的呼吸力学指标,采集T_0、T_3时的动脉血和中心静脉血进行血气分析,计算氧合指数(OI)。用纤维支气管镜采集T_1、T_3时支气管肺泡灌洗液,采用ELISA法检测IL-6、IL-8及IL-10浓度的变化。结果与常规通气组比较,T_3时反比通气组PaO_2明显升高(P0.05);T1~T4时反比通气组气道峰压(Ppeak)和气道平台压(Pplat)明显降低(P0.05),PEEP和平均气道压(Pmean)明显升高(P0.05),肺的顺应性(CL)明显增加(P0.05);T3时反比通气组IL-6、IL-8和IL-10浓度明显降低(P0.05)。低氧血症常规通气组2例(5.0%),反比通气组1例(2.5%),两组差异无统计学意义。两组均未见苏醒延迟、肺不张和气胸等并发症。结论反比通气联合PEEP可改善通气和低氧血症,增加肺的顺应性,降低气道平台压,抑制炎症因子释放。     

Effect of methylprednisolone on the cytokine response in patients undergoing lung surgery

Tumour necrosis factor α (TNFα), interleukin-l α (IL-lα) and IL-6, when released in excess, have been suggested to be important host mediators of the immunoinflammatory response to injury and infections. Corticosteroids suppress this response in vitro. This study was undertaken to investigate if a single dose of methylprednisolone (MP) could modify the cytokine response in patients undergoing lung surgery. Twenty-one patients with lung cancer were allocated randomly to treatment with MP 30 mg/kg i.v. (MP group) or isotonic saline (control group). Patients were anaesthetized with a balanced anaesthesia combined with thoracic epidural anaesthesia. MP or saline was administered immediately before induction of anaesthesia. The cytokines in plasma were measured by ELISA, and blood samples were collected preoperatively, at the end of surgery, 4 h later, and 1 and 5 days postoperatively. All patients had detectable IL-6 in plasma. Compared to preoperative values, plasma IL-6 levels in the MP group increased from 114 pg/ml (12–350 pg/ml) (mean, range) to peak value 146 pg/ml (15–580 pg/ml) on the first postoperative day. In the control group, IL-6 levels increased from 99 pg/ml (17–350 pg/ml) preoperatively to 125 pg/ml (10–300 pg/ml) on the first postoperative day. The increases were not significant. TNFα was detectable in only two patients, one from each group. Low levels of IL-la were demonstrated in three patients in the MP group and in four patients in the control group. In conclusion, the results of this study do not warrant steroid therapy as a modality to modify the secretion of cytokines in non-infected surgical patients, as the systemic cytokine responses were remarkably low.     

Beneficial effects of the prone position on the incidence of barotrauma in oleic acid-induced lung injury under continuous positive pressure ventilation

Background: Factors that contribute to ventilator-induced barotrauma are not well defined. This study investigates the effects of posture on ventilator-induced barotrauma, as well as arterial oxygenation. Methods: Twelve dogs with oleic acid lung injury, lying in the prone position (n=6) and right lateral position (n=6), were mechanically ventilated with continuous positive pressure ventilation for 24 hours. The incidence of pneumothorax and arterial oxygenation were investigated in each position. Results: All animals lying in the lateral position developed pneumothorax in the nondependent thorax, while only one animal in the prone position developed pneumothorax in the left thorax (P < 0.05). Postmortem examination revealed that in the lateral group, the nondependent lung consisted of large areas of emphysematous regions and neutrophil infiltration regions, while the dependent lung was composed of extensive atelectasis and neutrophil infiltration. Lung ruptures occurred in the non-dependent lung at the regions of either emphysematous change or severe neutrophil infiltration. In the prone group, in contrast, both lungs were inflated fairly homogeneously with only small areas of atelectatic and emphysematous changes. In the dog in whom pneumothorax developed, lung ruptures were limited to the regions of severe neutrophil infiltration in the left lung. No animal in either group had a peak airway pressure more than 20 cmH₂O. The peak airway pressures were 17.5 ±1.3 cmH₂O in the lateral group and 16.6±2.1 cmH₂O in the prone group (P>0.05). Tidal volume was comparable between the lateral group (13±2 ml/kg) and the prone group (12±1 ml/kg) before pneumothorax occurred (P>0.05). Arterial oxygenation was much better in the prone group than in the lateral group during the experiment (P < 0.05). Conclusion: It was concluded that in lung injury dogs, the prone position has beneficial effects on the incidence of ventilator-induced barotrauma and arterial oxygenation when compared with the lateral position. Ventilator-induced barotrauma may occur at lower airway pressure.     

Effect of positive end-expiratory pressure on inflammatory response in oleic acid-induced lung injury and whole-lung lavage-induced lung injury

Purpose The present study investigated the effects of positive end-expiratory pressure (PEEP) on the inflammatory response in two different lung injury models: edematous lung induced by oleic acid (OA); and atelectatic lung induced by whole-lung lavage (LAV). Methods Japanese white rabbits (n = 28) were allocated to one of the two lung injury (OA or LAV) groups, and each group was treated with intermittent positive pressure ventilation, using zero end-expiratory pressure (ZEEP) or PEEP (1 cm H₂O above the lower inflection point [LIP]). Thus, the animals were divided into LAV-ZEEP, LAV-PEEP, OA-ZEEP, and OA-PEEP groups. Blood and bronchoalveolar lavage fluid (BALF) were sampled 3 h after ventilatory treatment to analyze interleukin (IL)-8 levels. Results Pa_{O 2} was significantly decreased after the induction of lung injury, but was significantly higher in the PEEP groups compared to the ZEEP groups for each lung injury. Serum IL-8 levels were elevated in both experimental models. Serum IL-8 levels were significantly lower in LAV-PEEP than in LAV-ZEEP, whereas no difference was noted between OA-PEEP and OA-ZEEP. BALF IL-8 levels were lower in LAV-PEEP than in LAV-ZEEP. PEEP above LIP attenuated the elevation of IL-8 in BALF and serum in atelectatic lungs, but did not attenuate these increases in the edematous lungs. Conclusion These results suggest that the protective effects of PEEP on injured lungs may depend on the underlying lung pathology.