Significance of the changes in the respiratory system pressure-volume curve during acute lung injury in rats

The hypothesis that the changes in the respiratory system pressure- volume (PV) curve during pulmonary edema mainly reflect distal airway obstruction was investigated in rats. Normal rats had a well-defined upper inflection point (UIP) at low airway pressure. Airway occlusion by liquid instillation decreased compliance (Crs) and the volume (Vuip) of the UIP, and increased end-inspiratory pressure. The same changes were observed during the progression of edema produced by high volume ventilation (HV). Changes in Vuip and in Crs produced by HV were correlated with edema severity in normal rats or rats with lungs preinjured with alpha-naphthylthiourea. Vuip and Crs changes were proportional, reflecting compression of the PV curve on the volume axis and suggesting reduction of the amount of ventilatable lung at low airway pressure. In keeping with this explanation, the lower Vuip and Crs were before HV, the more severe HV-induced edema was in alpha-naphthylthiourea-injected rats. When edema was profuse, PV curves displayed a marked lower inflection point (LIP), the UIP at low pressure disappeared but another was seen at high volume above the LIP, and the correlation between Vuip changes and edema severity was lost. These observations may have clinical relevance in the context of the "open lung" strategy. Keywords: ventilator-induced lung injury; respiratory mechanics; acute respiratory distress syndrome     

Safety of pressure-volume curve measurement in acute lung injury and ARDS using a syringe technique

STUDY OBJECTIVES: To assess the safety of frequent pressure-volume (PV) curve measurement in patients with acute lung injury (ALI)/ARDS. DESIGN: Prospective observational study. SETTING: Academic medical-surgical critical care unit. PATIENTS: Consecutive patients with ALI or ARDS. INTERVENTIONS: Static inspiratory PV curves of the respiratory system were determined twice on day 1, then once daily for up to 6 days using a syringe. At each time point, three separate measurements of the PV curve were made. A 100-mL graduated syringe was used to inflate patients' lungs with 50- to 100-mL increments up to an airway pressure of 45 cm H(2)O or a total volume of 2 L; each volume step was maintained for 2 to 3 s until a plateau airway pressure was recorded. Outcome measures were mean arterial BP, heart rate (HR), and oxyhemoglobin saturation (SpO(2)) prior to and immediately after PV curve measurement. There were a priori criteria for procedure discontinuation if poorly tolerated. MEASUREMENTS AND RESULTS: Eleven patients were enrolled with a total of 134 PV curves generated. SpO(2) was 93 +/- 4% (mean +/- SD) before and fell to a nadir of 89 +/- 5% during PV curve measurement (p < 0.001), but increased to 97 +/- 4% immediately afterwards (p < 0.001, before vs after). HR rose from 106 +/- 22 to 108 +/- 22 beats/min immediately after the maneuver (p < 0.001). Mean arterial BP was 93 +/- 15 mm Hg before and 100 +/- 17 mm Hg immediately afterwards (p < 0.001). During PV curve measurement, systolic BP in one patient fell to 64 mm Hg from 113 mm Hg; in another patient, SpO(2) dropped to 79% from 89%. Both changes were transient. The study was discontinued in one patient because of inability to tolerate zero positive end-expiratory pressure; in another patient, the study was discontinued because of the development of subcutaneous emphysema. CONCLUSIONS: PV curve measurement by syringe technique is well tolerated in most patients. Nonetheless, the maneuver may cause significant changes in oxygenation and/or hemodynamics, necessitating close monitoring.     

Correlation between pulmonary fibrosis and the lung pressure-volume curve

The severity of pulmonary fibrosis is the main prognostic factor for survival of patients with interstitial lung diseases (ILD). Unfortunately, lung biopsy, which is the best method to assess fibrosis quantitatively, is done only once during the evolution of the disease. In this study we analyzed the relationship between the degree of fibrosis and the exponential constant k, derived from the lung pressure-volume curve (LPVC) in 33 patients with chronic ILD, 19 with pigeon breeder's disease (PBD), and 14 with idiopathic pulmonary fibrosis (IPF). Pulmonary function tests, including the LPVC, were obtained before biopsy. A semiquantitative histologic assessment of the severity of fibrosis was performed on lung tissues. All patients showed a decrease of total lung capacity, residual volume, compliance, and PaO₂. The mean value of the constant k was 0.08 ± 0.06. When expressed as a percent of normal values, 25 patients exhibited values of k lower than 70% of predicted; of the remaining 8 patients whose values were above 70% of predicted, 7 had PBD and only one IPF. On morphologic analysis, 19 patients displayed more than 50% fibrosis. No significant correlations were found between the extent of the lesion or severity of lung fibrosis and the conventional pulmonary function tests. By contrast, a moderate but significant correlation was found between k and the severity of lung fibrosis (r = –0.38, p < 0.05). These findings show that the shape of the LPVC, represented by the constant k, predicts the degree of lung fibrosis and could be useful in the clinical assessment and follow-up of patients with ILD. Offprint requests to: M. Selman     

Exponential analysis of the lung pressure-volume curve in patients with chronic pigeon-breeder's lung.

Pigeon-breeder's lung (PBL) is extremely common in Mexico City and often progresses to irreversible pulmonary fibrosis. The exponential analysis of the lung pressure-volume (PV) curve (V = A - Be-kp) has been suggested as a method to separate the lung restriction caused by inflammation from that caused by pulmonary fibrosis; a significantly decreased value for the exponential constant, k, suggests a change in the mechanical properties of the functioning lung parenchyma, while a normal value accompanied by restriction suggests subtraction of lung units without a change in the mechanical properties of the functioning units. We measured lung volumes and static PV curves in 29 patients who had persistent lung restriction following a biopsy-proven diagnosis of PBL. Mean values in the 29 subjects were as follows: age, 43 +/- 13 years; TLC, 61 +/- 15 percent of predicted; VC, 46 +/- 19 percent of predicted; and k, 55 +/- 17 percent of predicted. Twenty-four of the 29 patients had values for k that were below the 95 percent confidence level, and five had "normal" values. There was no difference in TLC and VC (percent of predicted) between those with or without a decreased value for k. Four of five patients with a normal value for k improved subsequent to diagnosis, while only one of 21 patients with a decreased k improved. We conclude that increased lung elasticity manifested by a low value for k is common in patients with chronic PBL. These results support the observation of frequent irreversible lung fibrosis in these patients. Measurements of k could prove a good prognostic indicator at the time of initial diagnosis.     

The relationship between gas delivery patterns and the lower inflection point of the pressure-volume curve during partial liquid ventilation

STUDY QUESTION: To determine whether a positive end-expiratory pressure (PEEP) level equivalent to the lower inflection point (LIP) could be identified by evaluation of the airway pressure, flow (f1. gif" BORDER="0">), and volume vs time waveforms during partial liquid ventilation (PLV). DESIGN: Prospective application of PEEP during PLV in a healthy animal model. SETTING: University hospital animal laboratory. PARTICIPANTS: Five healthy sheep weighing 30 kg each. INTERVENTIONS: The sequential application of 0 to 20 cm H(2)O PEEP in 2.5-cm H(2)O steps during PLV with both pressure and volume ventilation. MEASUREMENTS: Analysis of the pressure, volume, and f1. gif" BORDER="0"> waveforms as PEEP is sequentially increased. RESULTS: At 0 cm H(2)O PEEP, VT was markedly reduced compared with PEEP VT at > or = 7.5 cm H(2)O (p < 0.05) in pressure control ventilation (PCV), and peak inspiratory pressure minus PEEP was markedly increased compared with PEEP at > or = 5.0 cm H(2)O (p < 0.05) in volume control ventilation. At 10 cm H(2)O PEEP, all waveforms began to stabilize, and no significant differences in any variable assessed were measured at > 12.5 cm H(2)O PEEP. CONCLUSIONS: The application of PEEP during PLV markedly alters airway waveforms. Low PEEP decreases VT in PCV and increases airway pressure in VCV. The PEEP level equal to the LIP during PLV can be grossly estimated from airway waveforms. PEEP at > or = 10 cm H(2)O is needed to normalize gas delivery to functional residual capacity in the uninjured lung that is partially filled with perfluorocarbon.     

急性肺损伤发病机制的研究进展

急性肺损伤（ALI）是临床常见的急危重症,病死率高,多年来对其发病机制进行了大量的研究。随着失控的炎症反应引发多器官功能紊乱综合征理论的出现,对ALI的认识转向对炎症发生、调控的认识,参与炎症的炎症细胞和细胞因子则成为研究的热点,这些细胞和细胞因子、炎症介质构成了ALI炎症反应和免疫调节的“细胞网络”和“细胞因子网络”在其发病过程中发挥重要作用,本文将对近年来的研究做一综述。     

压力-容量曲线对急性肺损伤家兔实行个体化保护性通气的应用

目的研究以压力容量（P-V）曲线确定通气参数对急性肺损伤家兔肺的保护作用。方法新西兰家兔24只,随机分为4组（V1P1、V1P2、V2P1、V2P2）,每组4只。用油酸复制急性肺损伤模型,测定P-V曲线,以下曲点压力（Pinf）和上曲点压力（Pdef）分别选择呼气末正压（PEEP）的两水平：P1＝PinfP2＝Pinf－3cmH2O,潮气量（VT）两水平：V1＝15ml／kg,V2下调使平台压小于上曲点压力（Pplat＜Pdef）。观察肺力学、血气、血循环及肺病理改变。结果4组氧合效果基本相同,动脉血二氧化碳分压（PaCO2）和pH主要受VT影响。平均动脉压在大PEEP和（或）大VT时有所下降。呼吸系统静态顺应性（Cst）则以PEEP为Pinf时改善最明显,但大VT抵消了其作用且对肺泡有明显的损伤。小PEEP组肺泡透明膜变加重。结论以呼吸系统P-V曲线选择PEEP和VT进行个体化通气,对肺的力学特性和肺的病理性损伤有明显的保护作用,可能有利于改善急性肺损伤的预后。     

应用肺动态压力-容积曲线低位转折点选择最佳呼气末正压的研究

目的探讨根据动态肺压力-容积曲线低位转折点压力(Pinf)选择急性呼吸窘迫综合征(ARDS)患者最佳呼气末正压(PEEP)的可行性.方法以8例早期ARDS患者为研究对象,测定动态肺压力-容积曲线及Pinfd.采用低流速法测定准静态肺压力-容积曲线,并确定静态肺压力-容积曲线低位转折点压力(Pinfs).调整PEEP水平,观察患者血流动力学、肺机械力学和氧代谢的变化.结果当PEEP从Pinfd-6cmH2O水平增加到Pinfd+6cmH2O时,动脉血氧分压、动脉血氧饱和度、气道平均压和气道峰压均显著增加.与Pinfd+6cmH2O比较,Pinfd-4cmH2O时的动态肺顺应性显著增高.Pinfd+6cmH2O时的心脏指数有降低趋势,Pinfd-4cmH2O时的氧输送有升高趋势.当Pinfd为(12.8±3.2)cmH2O,Pinfs为(11.0±3.2)cmH2O,两者具有正相关性(r=0.99,P《0.05).回归方程为Pinfd=1.66+1.01×Pinfs.结论当ARDS患者行机械通气治疗时,Pinfd-4cmH2O或Pinfs-2cmH2O为最佳PEEP,可获得最大氧输送.     

急性肺损伤的氧化作用与抗氧化研究进展

急性肺损伤(ALI)是临床常见的呼吸系统急症,发病率高,确切发病机制不甚明确,临床治疗效果欠佳。本文对近几年ALI的氧化作用研究和抗氧化对ALI的治疗作用和相关研究进展,以及抗氧化作用对ALI的治疗前景作一综述。     

压力—容量曲线对急性肺损伤家兔实行个体化保护性通气？…

OBJECTIVE: To explore the lung-protective effect of ventilation with tidal volume and PEEP determined on pressure-volume curve in oleic acid rabbit models of acute lung injury. METHODS: 24 New Zealand rabbits were randomly divided into 4 groups (V1P1, V1P2, V2P1, V2P2). After inducing lung injury, the P-V curves were measured and drawn. The low and upper inflection point pressure (Pinf and Pdef respectively) were manually determined. Two levels of tidal volume (V1 = 15 ml/kg, V2 reduced for Pplat < Pdef) and two levels of PEEP (P1 = Pinf, P2 = Pinf - 3 cm H2O) were selected. The peak airway pressure (PIP), plateau pressure (Pplat), mean pressure (PAW), static compliance (Cst), heart rate, arterial blood pressure and blood-gas analysis were measured. The lung tissues were pathologically analyzed with light microscope. RESULTS: The oxygenation was not significantly different among 4 groups. The reduced VT significantly raised PaCO2 and lowered pH. Larger VT reduced arterial blood pressure. VT and PEEP synergetically raised airway pressure. Larger PEEP improved Cst, which was counteracted by larger VT. Reduced VT significantly lessened alveolar barotrauma. Larger PEEP lightened alveolar hyaline membrane formation and hemorrhage. CONCLUSION: The ventilation with VT and PEEP determined on P-V curve has significant protective effect on the acutely injured lung.     

急性肺损伤/急性呼吸窘迫综合征近年来国内研究进展

急性肺损伤／急性呼吸窘迫综合征(ALL／ARDS)的诊治近些年来愈来愈受到呼吸和危重病专业领域医务人员的重视，去冬今春严重急性呼吸综合征(SARS)的爆发更加突出了深入研究ALL／ARDS的紧迫性。自20世纪80年代在中华医学会呼吸病学分会和《中华结核和呼吸杂志》倡导下召开了成人呼吸窘迫综合征研讨会以来，以后分别于1993年     

急性肺损伤干细胞修复的研究进展

急性肺损伤/急性呼吸窘迫综合征的重要病理改变是肺泡上皮损伤,进而引起肺泡-毛细血管膜的损伤,出现气体弥散障碍。肺内自身存在及肺外组织来源的干细胞在肺损伤时可分化为上皮细胞,修复损伤肺组织的结构和功能,发挥治疗作用。本文就近年来国外对这方面的研究作一综述。     

输血相关急性肺损伤的研究进展

输血相关急性肺损伤(transfusion-related acute lung injury,TRALI)是输血引起的急性呼吸窘迫综合征。但是由于临床症状的非特异性、临床诊断的排他性以及试验室检查的复杂性,临床上往往对其认识不足。本文概述了近年来对TRALI的研究进展,阐述其发病机制,进一步加强对TRALI的认识,以便早期诊断和治疗。     

脑卒中与急性肺损伤的临床研究

目的 了解脑卒中并发急性肺损伤(ALI)的发生、发展过程,并对其危险因素进行探讨.方法 1999年2～9月收治的急性脑卒中患者64例,随机分为脑卒中并发ALI组31例,男23例,女8例,平均年龄(67±8)岁;脑卒中未并发ALI组33例,男21例,女12例,平均年龄(62±10)岁.对两组的年龄、性别、脑卒中类型以及急性期脑功能指标和肺功能指标进行分析比较.结果 高龄、意识障碍、哥拉斯格-匹斯堡昏迷评分(GCS-P)降低、咳嗽反射减弱、吞咽困难、鼻胃管饲、下呼吸道感染和发热等是ALI的重要危险因素;性别、脑卒中类型、病前呼吸道疾病史和有无呕吐无统计学意义.ALI组入院第1天(脑卒中发病第1～3天),ALI的发生率为19%,入院第3天增至81%,第5天高达95%.给氧治疗前,动脉血氧分压是判断ALI的重要指标;给氧治疗后,用氧合指数(PaO2/FiO2)反映ALI状况更为准确合理.结论 脑卒中急性期脑功能损伤严重或并发下呼吸道感染者,ALI发生率明显增高,尤其是老年人.     

Transfusion-related acute lung injury

Transfusion-related acute lung injury is a life-threatening complication of hemotherapy associated with the transfusion of plasma-containing blood products. It is characterized by acute respiratory distress, pulmonary edema and hypoxemia. Although its frequency is unknown, Food and Drug Administration data suggest that it is the third most common cause of transfusion-associated deaths, representing 9% of reported cases. Males and females of all ages are at equal risk. To date, there is no recognized profile of individuals who are at increased risk for this complication. Although there are two purported mechanisms of injury, the preponderance of evidence suggests that passively transfused complement-activating antibodies (either granulocyte or HLA-specific) act as mediators, which result in granulocyte aggregation, activation, and microvascular pulmonary injury. With appropriate respiratory intervention, most patients recover within 96 hours of the original insult and without permanent pulmonary sequelae.     

Transfusion-related acute lung injury

Transfusion-related acute lung injury (TRALI) is a life-threatening adverse event of transfusion, which has an increasing incidence in the United States and is the leading cause of transfusion-related death. TRALI and acute lung injury (ALI) share a common clinical definition except that TRALI is temporally- and mechanistically-related to transfusion of blood or blood components. A number of different models have been proposed to explain the pathogenesis. The first is an antibody-mediated event whereby transfusion of anti-HLA, class I or class II, or anti-granulocyte antibodies into patients whose leukocytes express the cognate antigens. The antibody:antigen interaction causes complement-mediated pulmonary sequestration and activation of neutrophils (PMNs) resulting in TRALI. The second is a two-event model: the first event is the clinical condition of the patient resulting in pulmonary endothelial activation and PMN sequestration, and the second event is the transfusion of a biologic response modifier (including anti-granulocyte antibodies, lipids, and CD40 ligand) that activates these adherent PMNs resulting in endothelial damage, capillary leak, and TRALI. These hypotheses are discussed with respect to animal models and human studies that provide the experimental and clinical relevance. The definition of TRALI, patient predisposition, treatment, prevention and reporting guidelines are also examined.